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Sample records for models provide insight

  1. Modeling fMRI signals can provide insights into neural processing in the cerebral cortex.

    Science.gov (United States)

    Vanni, Simo; Sharifian, Fariba; Heikkinen, Hanna; Vigário, Ricardo

    2015-08-01

    Every stimulus or task activates multiple areas in the mammalian cortex. These distributed activations can be measured with functional magnetic resonance imaging (fMRI), which has the best spatial resolution among the noninvasive brain imaging methods. Unfortunately, the relationship between the fMRI activations and distributed cortical processing has remained unclear, both because the coupling between neural and fMRI activations has remained poorly understood and because fMRI voxels are too large to directly sense the local neural events. To get an idea of the local processing given the macroscopic data, we need models to simulate the neural activity and to provide output that can be compared with fMRI data. Such models can describe neural mechanisms as mathematical functions between input and output in a specific system, with little correspondence to physiological mechanisms. Alternatively, models can be biomimetic, including biological details with straightforward correspondence to experimental data. After careful balancing between complexity, computational efficiency, and realism, a biomimetic simulation should be able to provide insight into how biological structures or functions contribute to actual data processing as well as to promote theory-driven neuroscience experiments. This review analyzes the requirements for validating system-level computational models with fMRI. In particular, we study mesoscopic biomimetic models, which include a limited set of details from real-life networks and enable system-level simulations of neural mass action. In addition, we discuss how recent developments in neurophysiology and biophysics may significantly advance the modelling of fMRI signals. Copyright © 2015 the American Physiological Society.

  2. Quantitative Hydraulic Models Of Early Land Plants Provide Insight Into Middle Paleozoic Terrestrial Paleoenvironmental Conditions

    Science.gov (United States)

    Wilson, J. P.; Fischer, W. W.

    2010-12-01

    Fossil plants provide useful proxies of Earth’s climate because plants are closely connected, through physiology and morphology, to the environments in which they lived. Recent advances in quantitative hydraulic models of plant water transport provide new insight into the history of climate by allowing fossils to speak directly to environmental conditions based on preserved internal anatomy. We report results of a quantitative hydraulic model applied to one of the earliest terrestrial plants preserved in three dimensions, the ~396 million-year-old vascular plant Asteroxylon mackei. This model combines equations describing the rate of fluid flow through plant tissues with detailed observations of plant anatomy; this allows quantitative estimates of two critical aspects of plant function. First and foremost, results from these models quantify the supply of water to evaporative surfaces; second, results describe the ability of plant vascular systems to resist tensile damage from extreme environmental events, such as drought or frost. This approach permits quantitative comparisons of functional aspects of Asteroxylon with other extinct and extant plants, informs the quality of plant-based environmental proxies, and provides concrete data that can be input into climate models. Results indicate that despite their small size, water transport cells in Asteroxylon could supply a large volume of water to the plant's leaves--even greater than cells from some later-evolved seed plants. The smallest Asteroxylon tracheids have conductivities exceeding 0.015 m^2 / MPa * s, whereas Paleozoic conifer tracheids do not reach this threshold until they are three times wider. However, this increase in conductivity came at the cost of little to no adaptations for transport safety, placing the plant’s vegetative organs in jeopardy during drought events. Analysis of the thickness-to-span ratio of Asteroxylon’s tracheids suggests that environmental conditions of reduced relative

  3. An integrated Biophysical CGE model to provide Sustainable Development Goal insights

    Science.gov (United States)

    Sanchez, Marko; Cicowiez, Martin; Howells, Mark; Zepeda, Eduardo

    2016-04-01

    Future projected changes in the energy system will inevitably result in changes to the level of appropriation of environmental resources, particularly land and water, and this will have wider implications for environmental sustainability, and may affect other sectors of the economy. An integrated climate, land, energy and water (CLEW) system will provide useful insights, particularly with regard to the environmental sustainability. However, it will require adequate integration with other tools to detect economic impacts and broaden the scope for policy analysis. A computable general equilibrium (CGE) model is a well suited tool to channel impacts, as detected in a CLEW analysis, onto all sectors of the economy, and evaluate trade-offs and synergies, including those of possible policy responses. This paper will show an application of such integration in a single-country CGE model with the following key characteristics. Climate is partly exogenous (as proxied by temperature and rainfall) and partly endogenous (as proxied by emissions generated by different sectors) and has an impact on endogenous variables such as land productivity and labor productivity. Land is a factor of production used in agricultural and forestry activities which can be of various types if land use alternatives (e.g., deforestation) are to be considered. Energy is an input to the production process of all economic sectors and a consumption good for households. Because it is possible to allow for substitution among different energy sources (e.g. renewable vs non-renewable) in the generation of electricity, the production process of energy products can consider the use of natural resources such as oil and water. Water, data permitting, can be considered as an input into the production process of agricultural sectors, which is particularly relevant in case of irrigation. It can also be considered as a determinant of total factor productivity in hydro-power generation. The integration of a CLEW

  4. Molecular modeling of human neutral sphingomyelinase provides insight into its molecular interactions.

    Science.gov (United States)

    Dinesh; Goswami, Angshumala; Suresh, Panneer Selvam; Thirunavukkarasu, Chinnasamy; Weiergräber, Oliver H; Kumar, Muthuvel Suresh

    2011-01-01

    The neutral sphingomyelinase (N-SMase) is considered a major candidate for mediating the stress-induced production of ceramide, and it plays an important role in cell-cycle arrest, apoptosis, inflammation, and eukaryotic stress responses. Recent studies have identified a small region at the very N-terminus of the 55 kDa tumour necrosis factor receptor (TNF-R55), designated the neutral sphingomyelinase activating domain (NSD) that is responsible for the TNF-induced activation of N-SMase. There is no direct association between TNF-R55 NSD and N-SMase; instead, a protein named factor associated with N-SMase activation (FAN) has been reported to couple the TNF-R55 NSD to N-SMase. Since the three-dimensional fold of N-SMase is still unknown, we have modeled the structure using the protein fold recognition and threading method. Moreover, we propose models for the TNF-R55 NSD as well as the FAN protein in order to study the structural basis of N-SMase activation and regulation. Protein-protein interaction studies suggest that FAN is crucially involved in mediating TNF-induced activation of the N-SMase pathway, which in turn regulates mitogenic and proinflammatory responses. Inhibition of N-SMase may lead to reduction of ceramide levels and hence may provide a novel therapeutic strategy for inflammation and autoimmune diseases. Molecular dynamics (MD) simulations were performed to check the stability of the predicted model and protein-protein complex; indeed, stable RMS deviations were obtained throughout the simulation. Furthermore, in silico docking of low molecular mass ligands into the active site of N-SMase suggests that His135, Glu48, Asp177, and Asn179 residues play crucial roles in this interaction. Based on our results, these ligands are proposed to be potent and selective N-SMase inhibitors, which may ultimately prove useful as lead compounds for drug development.

  5. An Analytical Model That Provides Insights into Various C2 Issues

    National Research Council Canada - National Science Library

    Taylor, James G; Neta, Beny; Shugart, Peter A

    2004-01-01

    .... A Lanchester-type model of force-on-force combat that reflects C2 architecture at the platform level is developed through a detailed analysis of the target-engagement cycle for a single typical firer...

  6. fiReproxies: A computational model providing insight into heat-affected archaeological lithic assemblages.

    Science.gov (United States)

    Sorensen, Andrew C; Scherjon, Fulco

    2018-01-01

    Evidence for fire use becomes increasingly sparse the further back in time one looks. This is especially true for Palaeolithic assemblages. Primary evidence of fire use in the form of hearth features tends to give way to clusters or sparse scatters of more durable heated stone fragments. In the absence of intact fireplaces, these thermally altered lithic remains have been used as a proxy for discerning relative degrees of fire use between archaeological layers and deposits. While previous experimental studies have demonstrated the physical effects of heat on stony artefacts, the mechanisms influencing the proportion of fire proxy evidence within archaeological layers remain understudied. This fundamental study is the first to apply a computer-based model (fiReproxies) in an attempt to simulate and quantify the complex interplay of factors that ultimately determine when and in what proportions lithic artefacts are heated by (anthropogenic) fires. As an illustrative example, we apply our model to two hypothetical archaeological layers that reflect glacial and interglacial conditions during the late Middle Palaeolithic within a generic simulated cave site to demonstrate how different environmental, behavioural and depositional factors like site surface area, sedimentation rate, occupation frequency, and fire size and intensity can, independently or together, significantly influence the visibility of archaeological fire signals.

  7. Directed evolution of a model primordial enzyme provides insights into the development of the genetic code.

    Directory of Open Access Journals (Sweden)

    Manuel M Müller

    Full Text Available The contemporary proteinogenic repertoire contains 20 amino acids with diverse functional groups and side chain geometries. Primordial proteins, in contrast, were presumably constructed from a subset of these building blocks. Subsequent expansion of the proteinogenic alphabet would have enhanced their capabilities, fostering the metabolic prowess and organismal fitness of early living systems. While the addition of amino acids bearing innovative functional groups directly enhances the chemical repertoire of proteomes, the inclusion of chemically redundant monomers is difficult to rationalize. Here, we studied how a simplified chorismate mutase evolves upon expanding its amino acid alphabet from nine to potentially 20 letters. Continuous evolution provided an enhanced enzyme variant that has only two point mutations, both of which extend the alphabet and jointly improve protein stability by >4 kcal/mol and catalytic activity tenfold. The same, seemingly innocuous substitutions (Ile→Thr, Leu→Val occurred in several independent evolutionary trajectories. The increase in fitness they confer indicates that building blocks with very similar side chain structures are highly beneficial for fine-tuning protein structure and function.

  8. Uranium sorption to natural substrates-insights provided by isotope exchange, selective extraction and surface complexation modelling approaches

    International Nuclear Information System (INIS)

    Waite, T.D.; Payne T.E.; Davis, J.A.

    1993-01-01

    An extensive experimental program has been conducted over the last three years into the interaction of U(VI) with both single oxides and clays and complex natural substrates from the weathered zone in the vicinity of a uranium ore body in northern Australia. While iron oxides have frequently been considered to account for much of the uptake on such natural substrates, the results of laboratory open-quotes pH edgeclose quotes studies and of isotope exchange and selective extraction studies suggest that other phases must also play a significant role in controlling the partitioning of U(VI) between solid and solution phases. Supporting studies on kaolinite, the dominant clay in this system, provide insight into the most appropriate method of modelling the interaction of U(VI) with these natural substrates. The problems still remaining in adequately describing sorption of radionuclides and trace elements to complex natural substrates are discussed

  9. Simulations of CYP51A from Aspergillus fumigatus in a model bilayer provide insights into triazole drug resistance.

    Science.gov (United States)

    Nash, Anthony; Rhodes, Johanna

    2018-04-01

    Azole antifungal drugs target CYP51A in Aspergillus fumigatus by binding with the active site of the protein, blocking ergosterol biosynthesis. Resistance to azole antifungal drugs is now common, with a leucine to histidine amino acid substitution at position 98 the most frequent, predominantly conferring resistance to itraconazole, although cross-resistance has been reported in conjunction with other mutations. In this study, we create a homology model of CYP51A using a recently published crystal structure of the paralog protein CYP51B. The derived structures, wild type, and L98H mutant are positioned within a lipid membrane bilayer and subjected to molecular dynamics simulations in order improve the accuracy of both models. The structural analysis from our simulations suggests a decrease in active site surface from the formation of hydrogen bonds between the histidine substitution and neighboring polar side chains, potentially preventing the binding of azole drugs. This study yields a biologically relevant structure and set of dynamics of the A. fumigatus Lanosterol 14 alpha-demethylase enzyme and provides further insight into azole antifungal drug resistance.

  10. Supplementary Material for: Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance

    KAUST Repository

    Phelan, Jody

    2016-01-01

    Abstract Background Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance. Methods To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods. Results The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites. Conclusions Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel

  11. Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance

    KAUST Repository

    Phelan, Jody

    2016-03-23

    Background Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance. Methods To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods. Results The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites. Conclusions Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel resistance

  12. Centromeric DNA characterization in the model grass Brachypodium distachyon provides insights on the evolution of the genus.

    Science.gov (United States)

    Li, Yinjia; Zuo, Sheng; Zhang, Zhiliang; Li, Zhanjie; Han, Jinlei; Chu, Zhaoqing; Hasterok, Robert; Wang, Kai

    2018-03-01

    Brachypodium distachyon is a well-established model monocot plant, and its small and compact genome has been used as an accurate reference for the much larger and often polyploid genomes of cereals such as Avena sativa (oats), Hordeum vulgare (barley) and Triticum aestivum (wheat). Centromeres are indispensable functional units of chromosomes and they play a core role in genome polyploidization events during evolution. As the Brachypodium genus contains about 20 species that differ significantly in terms of their basic chromosome numbers, genome size, ploidy levels and life strategies, studying their centromeres may provide important insight into the structure and evolution of the genome in this interesting and important genus. In this study, we isolated the centromeric DNA of the B. distachyon reference line Bd21 and characterized its composition via the chromatin immunoprecipitation of the nucleosomes that contain the centromere-specific histone CENH3. We revealed that the centromeres of Bd21 have the features of typical multicellular eukaryotic centromeres. Strikingly, these centromeres contain relatively few centromeric satellite DNAs; in particular, the centromere of chromosome 5 (Bd5) consists of only ~40 kb. Moreover, the centromeric retrotransposons in B. distachyon (CRBds) are evolutionarily young. These transposable elements are located both within and adjacent to the CENH3 binding domains, and have similar compositions. Moreover, based on the presence of CRBds in the centromeres, the species in this study can be grouped into two distinct lineages. This may provide new evidence regarding the phylogenetic relationships within the Brachypodium genus. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

  13. Can Economics Provide Insights into Trust Infrastructure?

    Science.gov (United States)

    Vishik, Claire

    Many security technologies require infrastructure for authentication, verification, and other processes. In many cases, viable and innovative security technologies are never adopted on a large scale because the necessary infrastructure is slow to emerge. Analyses of such technologies typically focus on their technical flaws, and research emphasizes innovative approaches to stronger implementation of the core features. However, an observation can be made that in many cases the success of adoption pattern depends on non-technical issues rather than technology-lack of economic incentives, difficulties in finding initial investment, inadequate government support. While a growing body of research is dedicated to economics of security and privacy in general, few theoretical studies in this area have been completed, and even fewer that look at the economics of “trust infrastructure” beyond simple “cost of ownership” models. This exploratory paper takes a look at some approaches in theoretical economics to determine if they can provide useful insights into security infrastructure technologies and architectures that have the best chance to be adopted. We attempt to discover if models used in theoretical economics can help inform technology developers of the optimal business models that offer a better chance for quick infrastructure deployment.

  14. Magnetotelluric 2D Modelling Provides Insight on the Structural Characteristics of the Guadalajara (Mexico) Triple Junction Domains

    Science.gov (United States)

    Arboleda Zapata, M. D. J., Sr.; Arzate-Flores, J.; Guevara Betancourt, R. E., Sr.

    2017-12-01

    The Jalisco Block is a continental microplate produced by the extension along three large structures: the Tepic-Zacoalco rift (TZR), the Colima rift (CR) and the Chapala rift that converge in a triple junction 50 km southwest of Guadalajara, Mexico, with orientation NW-SE, N-S, and E-W respectively. The present study focuses on investigating the deep structure of the north Colima and eastern Zacoalco grabens close to the Guadalajara triple junction (GTJ). This is a first study of its type that provide insight on the grabens structures and crustal characteristics underneath. We measured along two magnetotellurics (MT) profiles that cut perpendicularly the TZR (profile ZAC), and the northern CR (profile SAY) comprising a total of 24 broad band MT soundings. The ZAC profile has 11 stations and has a NE orientation, and the SAY profile has 14 station aligned E-W. Standard processing and editing procedures were completed, and distortion analysis was applied to the data set in order to define the dimensionality and electric strike of the separated profiles. Static shift was corrected using geology information to distinguish the different types of soundings and later averaging for those soundings located over the same lithology. The Bahr dimensionality parameters showed that the medium is mainly 3D for the SAY profile and 2D for the ZAC profile; furthermore, the regional geoelectric strike azimuth calculated with Bahr methodology were -4° and -48° respectively, with good concordance with the main surface structures. The tipper analysis permitted validated these results, as the real induction vectors were nearly perpendicular to main fault structures. All soundings were rotated to the respective regional strike and a 2D simultaneous inversion of the transverse electric (TE) mode, the transvers magnetic (TM) mode and the Tipper was completed. The RMS fitting error yield 3.2% for ZAC profile and 3.7% for SAY profile. Both profiles show a shallow conductive zone at north of

  15. A novel heart rate control model provides insights linking LF-HRV behavior to the open-loop gain.

    Science.gov (United States)

    Dvir, Hila; Bobrovsky, Ben Zion; Gabbay, Uri

    2013-09-20

    Low-frequency heart rate variability (LF-HRV) at rest has already been successfully modeled as self-sustained oscillations in a nonlinear control loop, but these models fail to simulate LF-HRV decreases either during aerobic exercise or in heart failure patients. Following control engineering practices, we assume the existence of a biological excitation (dither) within the heart rate control loop that softens the nonlinearity and studied LF-HRV behavior in a dither-embedded model. We adopted the Ottesen model with some revisions and induced a dither of high-frequency stochastic perturbations. We simulated scenarios of a healthy subject at rest and during aerobic exercise (by decreasing peripheral vascular resistance) and a heart failure patient (by decreasing stroke volume). The simulations resembled physiological LF-HRV behavior, i.e., LF-HRV decreased during aerobic exercise and in the heart failure patient. The simulations exhibited LF-HRV dependency on the open-loop gain, which is related to the product of the feedback gain and the feed forward gain. We are the first to demonstrate that LF-HRV may be dependent on the open-loop gain. Accordingly, reduced open-loop gain results in decreased LF-HRV, and vice versa. Our findings explain a well-known but unexplained observed phenomenon of reduced LF-HRV both in heart failure patients and in healthy subjects performing aerobic exercise. These findings have implications on how changes in LF-HRV can be interpreted physiologically, a necessary step towards the clinical utilization of LF-HRV. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Genome-scale metabolic modeling to provide insight into the production of storage compounds during feast-famine cycles of activated sludge.

    Science.gov (United States)

    Tajparast, Mohammad; Frigon, Dominic

    2013-01-01

    Studying storage metabolism during feast-famine cycles of activated sludge treatment systems provides profound insight in terms of both operational issues (e.g., foaming and bulking) and process optimization for the production of value added by-products (e.g., bioplastics). We examined the storage metabolism (including poly-β-hydroxybutyrate [PHB], glycogen, and triacylglycerols [TAGs]) during feast-famine cycles using two genome-scale metabolic models: Rhodococcus jostii RHA1 (iMT1174) and Escherichia coli K-12 (iAF1260) for growth on glucose, acetate, and succinate. The goal was to develop the proper objective function (OF) for the prediction of the main storage compound produced in activated sludge for given feast-famine cycle conditions. For the flux balance analysis, combinations of three OFs were tested. For all of them, the main OF was to maximize growth rates. Two additional sub-OFs were used: (1) minimization of biochemical fluxes, and (2) minimization of metabolic adjustments (MoMA) between the feast and famine periods. All (sub-)OFs predicted identical substrate-storage associations for the feast-famine growth of the above-mentioned metabolic models on a given substrate when glucose and acetate were set as sole carbon sources (i.e., glucose-glycogen and acetate-PHB), in agreement with experimental observations. However, in the case of succinate as substrate, the predictions depended on the network structure of the metabolic models such that the E. coli model predicted glycogen accumulation and the R. jostii model predicted PHB accumulation. While the accumulation of both PHB and glycogen was observed experimentally, PHB showed higher dynamics during an activated sludge feast-famine growth cycle with succinate as substrate. These results suggest that new modeling insights between metabolic predictions and population ecology will be necessary to properly predict metabolisms likely to emerge within the niches of activated sludge communities. Nonetheless

  17. Franchise Business Model: Theoretical Insights

    OpenAIRE

    Levickaitė, Rasa; Reimeris, Ramojus

    2010-01-01

    The article is based on literature review, theoretical insights, and deals with the topic of franchise business model. The objective of the paper is to analyse peculiarities of franchise business model and its developing conditions in Lithuania. The aim of the paper is to make an overview on franchise business model and its environment in Lithuanian business context. The overview is based on international and local theoretical insights. In terms of practical meaning, this article should be re...

  18. Close but no cigar: Spatial precision deficits following medial temporal lobe lesions provide novel insight into theoretical models of navigation and memory.

    Science.gov (United States)

    Kolarik, Branden S; Baer, Trevor; Shahlaie, Kiarash; Yonelinas, Andrew P; Ekstrom, Arne D

    2018-01-01

    Increasing evidence suggests that the human hippocampus contributes to a range of different behaviors, including episodic memory, language, short-term memory, and navigation. A novel theoretical framework, the Precision and Binding Model, accounts for these phenomenon by describing a role for the hippocampus in high-resolution, complex binding. Other theories like Cognitive Map Theory, in contrast, predict a specific role for the hippocampus in allocentric navigation, while Declarative Memory Theory predicts a specific role in delay-dependent conscious memory. Navigation provides a unique venue for testing these predictions, with past results from research with humans providing inconsistent findings regarding the role of the human hippocampus in spatial navigation. Here, we tested five patients with lesions primarily restricted to the hippocampus and those extending out into the surrounding medial temporal lobe cortex on a virtual water maze task. Consistent with the Precision and Binding Model, we found partially intact allocentric memory in all patients, with impairments in the spatial precision of their searches for a hidden target. We found similar impairments at both immediate and delayed testing. Our findings are consistent with the Precision and Binding Model of hippocampal function, arguing for its role across domains in high-resolution, complex binding. Remembering goal locations in one's environment is a critical skill for survival. How this information is represented in the brain is still not fully understood, but is believed to rely in some capacity on structures in the medial temporal lobe. Contradictory findings from studies of both humans and animals have been difficult to reconcile with regard to the role of the MTL, specifically the hippocampus. By assessing impairments observed during navigation to a goal in patients with medial temporal lobe damage we can better understand the role these structures play in such behavior. Utilizing virtual reality

  19. Physiologically-based pharmacokinetic modeling of tamoxifen and its metabolites in women of different CYP2D6 phenotypes provides new insight into the tamoxifen mass balance

    Directory of Open Access Journals (Sweden)

    Kristin eDickschen

    2012-05-01

    Full Text Available Tamoxifen is a first-line endocrine agent in the mechanism-based treatment of estrogen receptor positive (ER+ mammary carcinoma and applied to breast cancer patients all over the world. Endoxifen is a secondary and highly active metabolite of tamoxifen that is formed among others by the polymorphic cytochrome P450 2D6 (CYP2D6. It is widely accepted that CYP2D6 poor metabolizers (PM exert a pronounced decrease in endoxifen steady-state plasma concentrations compared to CYP2D6 extensive metabolizers (EM. Nevertheless, an in-depth understanding of the chain of cause and effect between CYP2D6 genotype, endoxifen steady-state plasma concentration, and subsequent tamoxifen treatment benefit still remains to be evolved.In this context, physiologically-based pharmacokinetic (PBPK-modeling provides a useful tool to mechanistically investigate the impact of CYP2D6 phenotype on endoxifen formation in female breast cancer patients undergoing tamoxifen therapy.It has long been thought that only a minor percentage of endoxifen is formed via 4-hydroxytamoxifen. However, the current investigation supports very recently published data that postulates a contribution of 4-hydroxytamoxifen above 20 % to total endoxifen formation. The developed PBPK-model describes tamoxifen PK in rats and humans. Moreover, tamoxifen metabolism in dependence of CYP2D6 phenotype in populations of European female individuals is well described, thus providing a good basis to further investigate the linkage of PK, mode of action, and treatment outcome in dependence of factors such as phenotype, ethnicity or co-treatment with CYP2D6 inhibitors.

  20. High Resolution Insights into Snow Distribution Provided by Drone Photogrammetry

    Science.gov (United States)

    Redpath, T.; Sirguey, P. J.; Cullen, N. J.; Fitzsimons, S.

    2017-12-01

    accumulation and ablation, snow depth maps provide geostatistically robust insights into seasonal snow processes, with unprecedented detail. Such data may enhance understanding of physical processes controlling spatial and temporal distribution of seasonal snow, and their relative importance at varying spatial and temporal scales.

  1. Induced seismicity provides insight into why earthquake ruptures stop

    KAUST Repository

    Galis, Martin

    2017-12-21

    Injection-induced earthquakes pose a serious seismic hazard but also offer an opportunity to gain insight into earthquake physics. Currently used models relating the maximum magnitude of injection-induced earthquakes to injection parameters do not incorporate rupture physics. We develop theoretical estimates, validated by simulations, of the size of ruptures induced by localized pore-pressure perturbations and propagating on prestressed faults. Our model accounts for ruptures growing beyond the perturbed area and distinguishes self-arrested from runaway ruptures. We develop a theoretical scaling relation between the largest magnitude of self-arrested earthquakes and the injected volume and find it consistent with observed maximum magnitudes of injection-induced earthquakes over a broad range of injected volumes, suggesting that, although runaway ruptures are possible, most injection-induced events so far have been self-arrested ruptures.

  2. Network models provide insights into how oriens–lacunosum-moleculare and bistratified cell interactions influence the power of local hippocampal CA1 theta oscillations

    Directory of Open Access Journals (Sweden)

    Katie A Ferguson

    2015-08-01

    Full Text Available Hippocampal theta is a 4-12 Hz rhythm associated with episodic memory, and although it has been studied extensively, the cellular mechanisms underlying its generation are unclear. The complex interactions between different interneuron types, such as those between oriens--lacunosum-moleculare (OLM interneurons and bistratified cells (BiCs, make their contribution to network rhythms difficult to determine experimentally. We created network models that are tied to experimental work at both cellular and network levels to explore how these interneuron interactions affect the power of local oscillations. Our cellular models were constrained with properties from patch clamp recordings in the CA1 region of an intact hippocampus preparation in vitro. Our network models are composed of three different types of interneurons: parvalbumin-positive (PV+ basket and axo-axonic cells (BC/AACs, PV+ BiCs, and somatostatin-positive OLM cells. Also included is a spatially extended pyramidal cell model to allow for a simplified local field potential representation, as well as experimentally-constrained, theta frequency synaptic inputs to the interneurons. The network size, connectivity, and synaptic properties were constrained with experimental data. To determine how the interactions between OLM cells and BiCs could affect local theta power, we explored a number of OLM-BiC connections and connection strengths.We found that our models operate in regimes in which OLM cells minimally or strongly affected the power of network theta oscillations due to balances that, respectively, allow compensatory effects or not. Inactivation of OLM cells could result in no change or even an increase in theta power. We predict that the dis-inhibitory effect of OLM cells to BiCs to pyramidal cell interactions plays a critical role in the power of network theta oscillations. Our network models reveal a dynamic interplay between different classes of interneurons in influencing local theta

  3. An Enumerative Combinatorics Model for Fragmentation Patterns in RNA Sequencing Provides Insights into Nonuniformity of the Expected Fragment Starting-Point and Coverage Profile.

    Science.gov (United States)

    Prakash, Celine; Haeseler, Arndt Von

    2017-03-01

    RNA sequencing (RNA-seq) has emerged as the method of choice for measuring the expression of RNAs in a given cell population. In most RNA-seq technologies, sequencing the full length of RNA molecules requires fragmentation into smaller pieces. Unfortunately, the issue of nonuniform sequencing coverage across a genomic feature has been a concern in RNA-seq and is attributed to biases for certain fragments in RNA-seq library preparation and sequencing. To investigate the expected coverage obtained from fragmentation, we develop a simple fragmentation model that is independent of bias from the experimental method and is not specific to the transcript sequence. Essentially, we enumerate all configurations for maximal placement of a given fragment length, F, on transcript length, T, to represent every possible fragmentation pattern, from which we compute the expected coverage profile across a transcript. We extend this model to incorporate general empirical attributes such as read length, fragment length distribution, and number of molecules of the transcript. We further introduce the fragment starting-point, fragment coverage, and read coverage profiles. We find that the expected profiles are not uniform and that factors such as fragment length to transcript length ratio, read length to fragment length ratio, fragment length distribution, and number of molecules influence the variability of coverage across a transcript. Finally, we explore a potential application of the model where, with simulations, we show that it is possible to correctly estimate the transcript copy number for any transcript in the RNA-seq experiment.

  4. Using pore-scale imaging and modeling to provide new insights in multi-phase flow, transport and reaction phenomena in porous media (Invited)

    Science.gov (United States)

    Bijeljic, B.; Andrew, M. G.; Menke, H. P.; Blunt, M. J.

    2013-12-01

    Advances in X ray imaging techniques made it possible not only to accurately describe solid and fluid(s) distributions in the pore space but also to study dynamics of multi-phase flow and reactive transport in-situ. This has opened up a range of new opportunities to better understand fundamental physics at the pore scale by experiment, and test and validate theoretical models in order to develop predictive tools at the pore scale and use it for upscaling. Firstly, we illustrate this concept by describing a new methodology for predicting non-Fickian transport in millimeter-sized three-dimensional micro-CT images of a beadpack, a sandstone, and a carbonate, representing porous media with an increasing degree of pore-scale complexity. The key strategy is to retain the full information on flow and transport signature of a porous medium by using probability distribution functions (PDFs) of voxel velocities for flow, and both PDFs of particle displacements and PDFs of particle transit times between voxels for transport. For this purpose, direct-simulation flow and transport model is used to analyse the relationship between pore structure, velocity, and the dynamics of the evolving plume. The model predictions for PDFs of particle displacements obtained by the model are in excellent agreement with those measured on similar cores in nuclear magnetic resonance experiments. A key determinant for non-Fickian transport is the spread in velocity distribution in the pore space. Further, we present micro-CT imaging of capillary trapping of scCO2 at reservoir conditions in a range of carbonates and sandstones having different pore structure and demonstrate that substantial quantities of scCO2 can be trapped in the pore space. Higher residual scCO2 saturations are found in sandstones compared to carbonates. The trapped ganglia exhibit different distribution of size, related to the inherent structure of pore space. Pore structures with large, open pores that are well connected lead

  5. The synthesis map is a multidimensional educational tool that provides insight into students' mental models and promotes students' synthetic knowledge generation.

    Science.gov (United States)

    Ortega, Ryan A; Brame, Cynthia J

    2015-01-01

    Concept mapping was developed as a method of displaying and organizing hierarchical knowledge structures. Using the new, multidimensional presentation software Prezi, we have developed a new teaching technique designed to engage higher-level skills in the cognitive domain. This tool, synthesis mapping, is a natural evolution of concept mapping, which utilizes embedding to layer information within concepts. Prezi's zooming user interface lets the author of the presentation use both depth as well as distance to show connections between data, ideas, and concepts. Students in the class Biology of Cancer created synthesis maps to illustrate their knowledge of tumorigenesis. Students used multiple organizational schemes to build their maps. We present an analysis of student work, placing special emphasis on organization within student maps and how the organization of knowledge structures in student maps can reveal strengths and weaknesses in student understanding or instruction. We also provide a discussion of best practices for instructors who would like to implement synthesis mapping in their classrooms. © 2015 R. A. Ortega and C. J. Brame et al. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  6. The Synthesis Map Is a Multidimensional Educational Tool That Provides Insight into Students’ Mental Models and Promotes Students’ Synthetic Knowledge Generation

    Science.gov (United States)

    Ortega, Ryan A.; Brame, Cynthia J.

    2015-01-01

    Concept mapping was developed as a method of displaying and organizing hierarchical knowledge structures. Using the new, multidimensional presentation software Prezi, we have developed a new teaching technique designed to engage higher-level skills in the cognitive domain. This tool, synthesis mapping, is a natural evolution of concept mapping, which utilizes embedding to layer information within concepts. Prezi’s zooming user interface lets the author of the presentation use both depth as well as distance to show connections between data, ideas, and concepts. Students in the class Biology of Cancer created synthesis maps to illustrate their knowledge of tumorigenesis. Students used multiple organizational schemes to build their maps. We present an analysis of student work, placing special emphasis on organization within student maps and how the organization of knowledge structures in student maps can reveal strengths and weaknesses in student understanding or instruction. We also provide a discussion of best practices for instructors who would like to implement synthesis mapping in their classrooms. PMID:25917385

  7. The complex jujube genome provides insights into fruit tree biology.

    Science.gov (United States)

    Liu, Meng-Jun; Zhao, Jin; Cai, Qing-Le; Liu, Guo-Cheng; Wang, Jiu-Rui; Zhao, Zhi-Hui; Liu, Ping; Dai, Li; Yan, Guijun; Wang, Wen-Jiang; Li, Xian-Song; Chen, Yan; Sun, Yu-Dong; Liu, Zhi-Guo; Lin, Min-Juan; Xiao, Jing; Chen, Ying-Ying; Li, Xiao-Feng; Wu, Bin; Ma, Yong; Jian, Jian-Bo; Yang, Wei; Yuan, Zan; Sun, Xue-Chao; Wei, Yan-Li; Yu, Li-Li; Zhang, Chi; Liao, Sheng-Guang; He, Rong-Jun; Guang, Xuan-Min; Wang, Zhuo; Zhang, Yue-Yang; Luo, Long-Hai

    2014-10-28

    The jujube (Ziziphus jujuba Mill.), a member of family Rhamnaceae, is a major dry fruit and a traditional herbal medicine for more than one billion people. Here we present a high-quality sequence for the complex jujube genome, the first genome sequence of Rhamnaceae, using an integrated strategy. The final assembly spans 437.65 Mb (98.6% of the estimated) with 321.45 Mb anchored to the 12 pseudo-chromosomes and contains 32,808 genes. The jujube genome has undergone frequent inter-chromosome fusions and segmental duplications, but no recent whole-genome duplication. Further analyses of the jujube-specific genes and transcriptome data from 15 tissues reveal the molecular mechanisms underlying some specific properties of the jujube. Its high vitamin C content can be attributed to a unique high level expression of genes involved in both biosynthesis and regeneration. Our study provides insights into jujube-specific biology and valuable genomic resources for the improvement of Rhamnaceae plants and other fruit trees.

  8. Comparative genomics provide insights into evolution of trichoderma nutrition style.

    Science.gov (United States)

    Xie, Bin-Bin; Qin, Qi-Long; Shi, Mei; Chen, Lei-Lei; Shu, Yan-Li; Luo, Yan; Wang, Xiao-Wei; Rong, Jin-Cheng; Gong, Zhi-Ting; Li, Dan; Sun, Cai-Yun; Liu, Gui-Ming; Dong, Xiao-Wei; Pang, Xiu-Hua; Huang, Feng; Liu, Weifeng; Chen, Xiu-Lan; Zhou, Bai-Cheng; Zhang, Yu-Zhong; Song, Xiao-Yan

    2014-02-01

    Saprotrophy on plant biomass is a recently developed nutrition strategy for Trichoderma. However, the physiology and evolution of this new nutrition strategy is still elusive. We report the deep sequencing and analysis of the genome of Trichoderma longibrachiatum, an efficient cellulase producer. The 31.7-Mb genome, smallest among the sequenced Trichoderma species, encodes fewer nutrition-related genes than saprotrophic T. reesei (Tr), including glycoside hydrolases and nonribosomal peptide synthetase-polyketide synthase. Homology and phylogenetic analyses suggest that a large number of nutrition-related genes, including GH18 chitinases, β-1,3/1,6-glucanases, cellulolytic enzymes, and hemicellulolytic enzymes, were lost in the common ancestor of T. longibrachiatum (Tl) and Tr. dN/dS (ω) calculation indicates that all the nutrition-related genes analyzed are under purifying selection. Cellulolytic enzymes, the key enzymes for saprotrophy on plant biomass, are under stronger purifying selection pressure in Tl and Tr than in mycoparasitic species, suggesting that development of the nutrition strategy of saprotrophy on plant biomass has increased the selection pressure. In addition, aspartic proteases, serine proteases, and metalloproteases are subject to stronger purifying selection pressure in Tl and Tr, suggesting that these enzymes may also play important roles in the nutrition. This study provides insights into the physiology and evolution of the nutrition strategy of Trichoderma.

  9. Can tobacco dependence provide insights into other drug addictions?

    Directory of Open Access Journals (Sweden)

    Joseph R. DiFranza

    2016-10-01

    Full Text Available Abstract Within the field of addiction research, individuals tend to operate within silos of knowledge focused on specific drug classes. The discovery that tobacco dependence develops in a progression of stages and that the latency to the onset of withdrawal symptoms after the last use of tobacco changes over time have provided insights into how tobacco dependence develops that might be applied to the study of other drugs. As physical dependence on tobacco develops, it progresses through previously unrecognized clinical stages of wanting, craving and needing. The latency to withdrawal is a measure of the asymptomatic phase of withdrawal, extending from the last use of tobacco to the emergence of withdrawal symptoms. Symptomatic withdrawal is characterized by a wanting phase, a craving phase, and a needing phase. The intensity of the desire to smoke that is triggered by withdrawal correlates with brain activity in addiction circuits. With repeated tobacco use, the latency to withdrawal shrinks from as long as several weeks to as short as several minutes. The shortening of the asymptomatic phase of withdrawal drives an escalation of smoking, first in terms of the number of smoking days/month until daily smoking commences, then in terms of cigarettes smoked/day. The discoveries of the stages of physical dependence and the latency to withdrawal raises the question, does physical dependence develop in stages with other drugs? Is the latency to withdrawal for other substances measured in weeks at the onset of dependence? Does it shorten over time? The research methods that uncovered how tobacco dependence emerges might be fruitfully applied to the investigation of other addictions.

  10. Eggshell Porosity Provides Insight on Evolution of Nesting in Dinosaurs.

    Directory of Open Access Journals (Sweden)

    Kohei Tanaka

    Full Text Available Knowledge about the types of nests built by dinosaurs can provide insight into the evolution of nesting and reproductive behaviors among archosaurs. However, the low preservation potential of their nesting materials and nesting structures means that most information can only be gleaned indirectly through comparison with extant archosaurs. Two general nest types are recognized among living archosaurs: 1 covered nests, in which eggs are incubated while fully covered by nesting material (as in crocodylians and megapodes, and 2 open nests, in which eggs are exposed in the nest and brooded (as in most birds. Previously, dinosaur nest types had been inferred by estimating the water vapor conductance (i.e., diffusive capacity of their eggs, based on the premise that high conductance corresponds to covered nests and low conductance to open nests. However, a lack of statistical rigor and inconsistencies in this method render its application problematic and its validity questionable. As an alternative we propose a statistically rigorous approach to infer nest type based on large datasets of eggshell porosity and egg mass compiled for over 120 extant archosaur species and 29 archosaur extinct taxa/ootaxa. The presence of a strong correlation between eggshell porosity and nest type among extant archosaurs indicates that eggshell porosity can be used as a proxy for nest type, and thus discriminant analyses can help predict nest type in extinct taxa. Our results suggest that: 1 covered nests are likely the primitive condition for dinosaurs (and probably archosaurs, and 2 open nests first evolved among non-avian theropods more derived than Lourinhanosaurus and were likely widespread in non-avian maniraptorans, well before the appearance of birds. Although taphonomic evidence suggests that basal open nesters (i.e., oviraptorosaurs and troodontids were potentially the first dinosaurs to brood their clutches, they still partially buried their eggs in sediment

  11. Eggshell Porosity Provides Insight on Evolution of Nesting in Dinosaurs.

    Science.gov (United States)

    Tanaka, Kohei; Zelenitsky, Darla K; Therrien, François

    2015-01-01

    Knowledge about the types of nests built by dinosaurs can provide insight into the evolution of nesting and reproductive behaviors among archosaurs. However, the low preservation potential of their nesting materials and nesting structures means that most information can only be gleaned indirectly through comparison with extant archosaurs. Two general nest types are recognized among living archosaurs: 1) covered nests, in which eggs are incubated while fully covered by nesting material (as in crocodylians and megapodes), and 2) open nests, in which eggs are exposed in the nest and brooded (as in most birds). Previously, dinosaur nest types had been inferred by estimating the water vapor conductance (i.e., diffusive capacity) of their eggs, based on the premise that high conductance corresponds to covered nests and low conductance to open nests. However, a lack of statistical rigor and inconsistencies in this method render its application problematic and its validity questionable. As an alternative we propose a statistically rigorous approach to infer nest type based on large datasets of eggshell porosity and egg mass compiled for over 120 extant archosaur species and 29 archosaur extinct taxa/ootaxa. The presence of a strong correlation between eggshell porosity and nest type among extant archosaurs indicates that eggshell porosity can be used as a proxy for nest type, and thus discriminant analyses can help predict nest type in extinct taxa. Our results suggest that: 1) covered nests are likely the primitive condition for dinosaurs (and probably archosaurs), and 2) open nests first evolved among non-avian theropods more derived than Lourinhanosaurus and were likely widespread in non-avian maniraptorans, well before the appearance of birds. Although taphonomic evidence suggests that basal open nesters (i.e., oviraptorosaurs and troodontids) were potentially the first dinosaurs to brood their clutches, they still partially buried their eggs in sediment. Open nests

  12. Social network analysis provides insights into African swine fever epidemiology.

    Science.gov (United States)

    Lichoti, Jacqueline Kasiiti; Davies, Jocelyn; Kitala, Philip M; Githigia, Samuel M; Okoth, Edward; Maru, Yiheyis; Bukachi, Salome A; Bishop, Richard P

    2016-04-01

    Pig movements play a significant role in the spread of economically important infectious diseases such as the African swine fever. Characterization of movement networks between pig farms and through other types of farm and household enterprises that are involved in pig value chains can provide useful information on the role that different participants in the networks play in pathogen transmission. Analysis of social networks that underpin these pig movements can reveal pathways that are important in the transmission of disease, trade in commodities, the dissemination of information and the influence of behavioural norms. We assessed pig movements among pig keeping households within West Kenya and East Uganda and across the shared Kenya-Uganda border in the study region, to gain insight into within-country and trans-boundary pig movements. Villages were sampled using a randomized cluster design. Data were collected through interviews in 2012 and 2013 from 683 smallholder pig-keeping households in 34 villages. NodeXL software was used to describe pig movement networks at village level. The pig movement and trade networks were localized and based on close social networks involving family ties, friendships and relationships with neighbours. Pig movement network modularity ranged from 0.2 to 0.5 and exhibited good community structure within the network implying an easy flow of knowledge and adoption of new attitudes and beliefs, but also promoting an enhanced rate of disease transmission. The average path length of 5 defined using NodeXL, indicated that disease could easily reach every node in a cluster. Cross-border boar service between Uganda and Kenya was also recorded. Unmonitored trade in both directions was prevalent. While most pig transactions in the absence of disease, were at a small scale (sales during ASF outbreaks were to traders or other farmers from outside the sellers' village at a range of >10km. The close social relationships between actors in pig

  13. Numerical Experiments Providing New Insights into Plasma Focus Fusion Devices

    Directory of Open Access Journals (Sweden)

    Sing Lee

    2010-04-01

    Full Text Available Recent extensive and systematic numerical experiments have uncovered new insights into plasma focus fusion devices including the following: (1 a plasma current limitation effect, as device static inductance is reduced towards very small values; (2 scaling laws of neutron yield and soft x-ray yield as functions of storage energies and currents; (3 a global scaling law for neutron yield as a function of storage energy combining experimental and numerical data showing that scaling deterioration has probably been interpreted as neutron ‘saturation’; and (4 a fundamental cause of neutron ‘saturation’. The ground-breaking insights thus gained may completely change the directions of plasma focus fusion research.

  14. Athena: Providing Insight into the History of the Universe

    Science.gov (United States)

    Murphy, Gloria A.

    2010-01-01

    The American Institute for Aeronautics and Astronautics has provided a Request for Proposal which calls for a manned mission to a Near-Earth Object. It is the goal of Team COLBERT to respond to their request by providing a reusable system that can be implemented as a solid stepping stone for future manned trips to Mars and beyond. Despite Team COLBERT consisting of only students in Aerospace Engineering, in order to achieve this feat, the team must employ the use of Systems Engineering. Tools and processes from Systems Engineering will provide quantitative and semi-quantitative tools for making design decisions and evaluating items such as budgets and schedules. This paper will provide an in-depth look at some of the Systems Engineering processes employed and will step through the design process of a Human Asteroid Exploration System.

  15. Military Medics Insight into Providing Womens Health Services

    Science.gov (United States)

    2015-12-22

    determining a patient’s preference in a provider rather than gender (Buck & Littleton, 2014). Medics, particularly male medics, were keenly aware of...KS, Littleton HL. (2014). Stereotyped beliefs about male and female OB-GYNS: relationship to provider choice and patient satisfaction. Journal of...health care resource during deployment. Male and female IDCs felt obligated to educate women about how to conduct themselves on ship. In a

  16. Habitat characteristics provide insights of carbon storage in seagrass meadows

    KAUST Repository

    Mazarrasa, Inés

    2018-02-17

    Seagrass meadows provide multiple ecosystem services, yet they are among the most threatened ecosystems on earth. Because of their role as carbon sinks, protection and restoration of seagrass meadows contribute to climate change mitigation. Blue Carbon strategies aim to enhance CO2 sequestration and avoid greenhouse gasses emissions through the management of coastal vegetated ecosystems, including seagrass meadows. The implementation of Blue Carbon strategies requires a good understanding of the habitat characteristics that influence Corg sequestration. Here, we review the existing knowledge on Blue Carbon research in seagrass meadows to identify the key habitat characteristics that influence Corg sequestration in seagrass meadows, those factors that threaten this function and those with unclear effects. We demonstrate that not all seagrass habitats have the same potential, identify research priorities and describe the implications of the results found for the implementation and development of efficient Blue Carbon strategies based on seagrass meadows.

  17. Habitat characteristics provide insights of carbon storage in seagrass meadows.

    Science.gov (United States)

    Mazarrasa, Inés; Samper-Villarreal, Jimena; Serrano, Oscar; Lavery, Paul S; Lovelock, Catherine E; Marbà, Núria; Duarte, Carlos M; Cortés, Jorge

    2018-02-16

    Seagrass meadows provide multiple ecosystem services, yet they are among the most threatened ecosystems on earth. Because of their role as carbon sinks, protection and restoration of seagrass meadows contribute to climate change mitigation. Blue Carbon strategies aim to enhance CO 2 sequestration and avoid greenhouse gasses emissions through the management of coastal vegetated ecosystems, including seagrass meadows. The implementation of Blue Carbon strategies requires a good understanding of the habitat characteristics that influence C org sequestration. Here, we review the existing knowledge on Blue Carbon research in seagrass meadows to identify the key habitat characteristics that influence C org sequestration in seagrass meadows, those factors that threaten this function and those with unclear effects. We demonstrate that not all seagrass habitats have the same potential, identify research priorities and describe the implications of the results found for the implementation and development of efficient Blue Carbon strategies based on seagrass meadows. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Plasmodium vivax Biology: Insights Provided by Genomics, Transcriptomics and Proteomics

    Science.gov (United States)

    Bourgard, Catarina; Albrecht, Letusa; Kayano, Ana C. A. V.; Sunnerhagen, Per; Costa, Fabio T. M.

    2018-01-01

    During the last decade, the vast omics field has revolutionized biological research, especially the genomics, transcriptomics and proteomics branches, as technological tools become available to the field researcher and allow difficult question-driven studies to be addressed. Parasitology has greatly benefited from next generation sequencing (NGS) projects, which have resulted in a broadened comprehension of basic parasite molecular biology, ecology and epidemiology. Malariology is one example where application of this technology has greatly contributed to a better understanding of Plasmodium spp. biology and host-parasite interactions. Among the several parasite species that cause human malaria, the neglected Plasmodium vivax presents great research challenges, as in vitro culturing is not yet feasible and functional assays are heavily limited. Therefore, there are gaps in our P. vivax biology knowledge that affect decisions for control policies aiming to eradicate vivax malaria in the near future. In this review, we provide a snapshot of key discoveries already achieved in P. vivax sequencing projects, focusing on developments, hurdles, and limitations currently faced by the research community, as well as perspectives on future vivax malaria research. PMID:29473024

  19. The genome of Laccaria bicolor provides insights into mycorrhizal symbiosis

    Energy Technology Data Exchange (ETDEWEB)

    Martin, F.; Aerts, A.; Ahren, D.; Brun, A.; Danchin, E. G. J.; Duchaussoy, F.; Gibon, J.; Kohler, A.; Lindquist, E.; Peresa, V.; Salamov, A.; Shapiro, H. J.; Wuyts, J.; Blaudez, D.; Buee, M.; Brokstein, P.; Canback, B.; Cohen, D.; Courty, P. E.; Coutinho, P. M.; Delaruelle, C.; Detter, J. C.; Deveau, A.; DiFazio, S.; Duplessis, S.; Fraissinet-Tachet, L.; Lucic, E.; Frey-Klett, P.; Fourrey, C.; Feussner, I.; Gay, G.; Grimwood, J.; Hoegger, P. J.; Jain, P.; Kilaru, S.; Labbe, J.; Lin, Y. C.; Legue, V.; Le Tacon, F.; Marmeisse, R.; Melayah, D.; Montanini, B.; Muratet, M.; Nehls, U.; Niculita-Hirzel, H.; Secq, M. P. Oudot-Le; Peter, M.; Quesneville, H.; Rajashekar, B.; Reich, M.; Rouhier, N.; Schmutz, J.; Yin, T.; Chalot, M.; Henrissat, B.; Kues, U.; Lucas, S.; Van de Peer, Y.; Podila, G. K.; Polle, A.; Pukkila, P. J.; Richardson, P. M.; Rouze, P.; Sanders, I. R.; Stajich, J. E.; Tunlid, A.; Tuskan, G.; Grigoriev, I. V.

    2007-08-10

    Mycorrhizal symbioses the union of roots and soil fungi are universal in terrestrial ecosystems and may have been fundamental to land colonization by plants 1, 2. Boreal, temperate and montane forests all depend on ectomycorrhizae1. Identification of the primary factors that regulate symbiotic development and metabolic activity will therefore open the door to understanding the role of ectomycorrhizae in plant development and physiology, allowing the full ecological significance of this symbiosis to be explored. Here we report the genome sequence of the ectomycorrhizal basidiomycete Laccaria bicolor (Fig. 1) and highlight gene sets involved in rhizosphere colonization and symbiosis. This 65-megabase genome assembly contains 20,000 predicted protein-encoding genes and a very large number of transposons and repeated sequences. We detected unexpected genomic features, most notably a battery of effector-type small secreted proteins (SSPs) with unknown function, several of which are only expressed in symbiotic tissues. The most highly expressed SSP accumulates in the proliferating hyphae colonizing the host root. The ectomycorrhizae-specific SSPs probably have a decisive role in the establishment of the symbiosis. The unexpected observation that the genome of L. bicolor lacks carbohydrate-active enzymes involved in degradation of plant cell walls, but maintains the ability to degrade non-plant cell wall polysaccharides, reveals the dual saprotrophic and biotrophic lifestyle of the mycorrhizal fungus that enables it to grow within both soil and living plant roots. The predicted gene inventory of the L. bicolor genome, therefore, points to previously unknown mechanisms of symbiosis operating in biotrophic mycorrhizal fungi. The availability of this genome provides an unparalleled opportunity to develop a deeper understanding of the processes by which symbionts interact with plants within their ecosystem to perform vital functions in the carbon and nitrogen cycles that are

  20. Variations upon a theme: Australian lizards provide insights into the endocrine control of vertebrate reproductive cycles.

    Science.gov (United States)

    Jones, Susan M

    2017-04-01

    Australian lizards exhibit a broad array of different reproductive strategies and provide an extraordinary diversity and range of models with which to address fundamental problems in reproductive biology. Studies on lizards have frequently led to new insights into hormonal regulatory pathways or mechanisms of control, but we have detailed knowledge of the reproductive cycle in only a small percentage of known species. This review provides an overview and synthesis of current knowledge of the hormonal control of reproductive cycles in Australian lizards. Agamid lizards have provided useful models with which to test hypotheses about the hormonal regulation of the expression of reproductive behaviors, while research on viviparous skinks is providing insights into the evolution of the endocrine control of gestation. However, in order to better understand the potential risks that environmental factors such as climate change and endocrine disrupting chemicals pose to our fauna, better knowledge is required of the fundamental characteristics of the reproductive cycle in a broader range of lizard species. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Multi-omics analysis provides insight to the Ignicoccus hospitalis-Nanoarchaeum equitans association.

    Science.gov (United States)

    Rawle, Rachel A; Hamerly, Timothy; Tripet, Brian P; Giannone, Richard J; Wurch, Louie; Hettich, Robert L; Podar, Mircea; Copié, Valerie; Bothner, Brian

    2017-09-01

    Studies of interspecies interactions are inherently difficult due to the complex mechanisms which enable these relationships. A model system for studying interspecies interactions is the marine hyperthermophiles Ignicoccus hospitalis and Nanoarchaeum equitans. Recent independently-conducted 'omics' analyses have generated insights into the molecular factors modulating this association. However, significant questions remain about the nature of the interactions between these archaea. We jointly analyzed multiple levels of omics datasets obtained from published, independent transcriptomics, proteomics, and metabolomics analyses. DAVID identified functionally-related groups enriched when I. hospitalis is grown alone or in co-culture with N. equitans. Enriched molecular pathways were subsequently visualized using interaction maps generated using STRING. Key findings of our multi-level omics analysis indicated that I. hospitalis provides precursors to N. equitans for energy metabolism. Analysis indicated an overall reduction in diversity of metabolic precursors in the I. hospitalis-N. equitans co-culture, which has been connected to the differential use of ribosomal subunits and was previously unnoticed. We also identified differences in precursors linked to amino acid metabolism, NADH metabolism, and carbon fixation, providing new insights into the metabolic adaptions of I. hospitalis enabling the growth of N. equitans. This multi-omics analysis builds upon previously identified cellular patterns while offering new insights into mechanisms that enable the I. hospitalis-N. equitans association. Our study applies statistical and visualization techniques to a mixed-source omics dataset to yield a more global insight into a complex system, that was not readily discernable from separate omics studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Structure of the Hantavirus Nucleoprotein Provides Insights into the Mechanism of RNA Encapsidation

    Directory of Open Access Journals (Sweden)

    Daniel Olal

    2016-03-01

    Full Text Available Hantaviruses are etiological agents of life-threatening hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome. The nucleoprotein (N of hantavirus is essential for viral transcription and replication, thus representing an attractive target for therapeutic intervention. We have determined the crystal structure of hantavirus N to 3.2 Å resolution. The structure reveals a two-lobed, mostly α-helical structure that is distantly related to that of orthobunyavirus Ns. A basic RNA binding pocket is located at the intersection between the two lobes. We provide evidence that oligomerization is mediated by amino- and C-terminal arms that bind to the adjacent monomers. Based on these findings, we suggest a model for the oligomeric ribonucleoprotein (RNP complex. Our structure provides mechanistic insights into RNA encapsidation in the genus Hantavirus and constitutes a template for drug discovery efforts aimed at combating hantavirus infections.

  3. Human acid sphingomyelinase structures provide insight to molecular basis of Niemann–Pick disease

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yan-Feng; Metcalf, Matthew C.; Garman, Scott C.; Edmunds, Tim; Qiu, Huawei; Wei, Ronnie R. (Sanofi Aventis); (UMASS, Amherst)

    2016-10-26

    Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann–Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site. The structures reveal the underlying catalytic mechanism, in which two zinc ions activate a water molecule for nucleophilic attack of the phosphodiester bond. Docking of sphingomyelin provides a model that allows insight into the selectivity of the enzyme and how the ASM domains collaborate to complete hydrolysis. Mapping of known mutations provides a basic understanding on correlations between enzyme dysfunction and phenotypes observed in ASMD patients.

  4. Deep transcriptome sequencing provides new insights into the structural and functional organization of the wheat genome.

    Science.gov (United States)

    Pingault, Lise; Choulet, Frédéric; Alberti, Adriana; Glover, Natasha; Wincker, Patrick; Feuillet, Catherine; Paux, Etienne

    2015-02-10

    Because of its size, allohexaploid nature, and high repeat content, the bread wheat genome is a good model to study the impact of the genome structure on gene organization, function, and regulation. However, because of the lack of a reference genome sequence, such studies have long been hampered and our knowledge of the wheat gene space is still limited. The access to the reference sequence of the wheat chromosome 3B provided us with an opportunity to study the wheat transcriptome and its relationships to genome and gene structure at a level that has never been reached before. By combining this sequence with RNA-seq data, we construct a fine transcriptome map of the chromosome 3B. More than 8,800 transcription sites are identified, that are distributed throughout the entire chromosome. Expression level, expression breadth, alternative splicing as well as several structural features of genes, including transcript length, number of exons, and cumulative intron length are investigated. Our analysis reveals a non-monotonic relationship between gene expression and structure and leads to the hypothesis that gene structure is determined by its function, whereas gene expression is subject to energetic cost. Moreover, we observe a recombination-based partitioning at the gene structure and function level. Our analysis provides new insights into the relationships between gene and genome structure and function. It reveals mechanisms conserved with other plant species as well as superimposed evolutionary forces that shaped the wheat gene space, likely participating in wheat adaptation.

  5. Hydrodeoxygenation by deuterium gas--a powerful way to provide insight into the reaction mechanisms.

    Science.gov (United States)

    Ben, Haoxi; Ferguson, Glen A; Mu, Wei; Pu, Yunqiao; Huang, Fang; Jarvis, Mark; Biddy, Mary; Deng, Yulin; Ragauskas, Arthur J

    2013-11-28

    This study demonstrates the use of isotopic labelling and NMR to study the HDO process. As far as we know, this is the first reported effort to trace the incorporation of hydrogen in the HDO process of lignin pyrolysis oil thereby providing key fundamental insight into its reaction mechanism.

  6. The Clean Energy Manufacturing Analysis Center (CEMAC): Providing Analysis and Insights on Clean Technology Manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Nicholi S [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-28

    The U.S. Department of Energy's Clean Energy Manufacturing Analysis Center (CEMAC) provides objective analysis and up-to-date data on global supply chains and manufacturing of clean energy technologies. Policymakers and industry leaders seek CEMAC insights to inform choices to promote economic growth and the transition to a clean energy economy.

  7. Mathematical modeling and comparison of protein size distribution in different plant, animal, fungal and microbial species reveals a negative correlation between protein size and protein number, thus providing insight into the evolution of proteomes

    Directory of Open Access Journals (Sweden)

    Tiessen Axel

    2012-02-01

    Full Text Available Abstract Background The sizes of proteins are relevant to their biochemical structure and for their biological function. The statistical distribution of protein lengths across a diverse set of taxa can provide hints about the evolution of proteomes. Results Using the full genomic sequences of over 1,302 prokaryotic and 140 eukaryotic species two datasets containing 1.2 and 6.1 million proteins were generated and analyzed statistically. The lengthwise distribution of proteins can be roughly described with a gamma type or log-normal model, depending on the species. However the shape parameter of the gamma model has not a fixed value of 2, as previously suggested, but varies between 1.5 and 3 in different species. A gamma model with unrestricted shape parameter described best the distributions in ~48% of the species, whereas the log-normal distribution described better the observed protein sizes in 42% of the species. The gamma restricted function and the sum of exponentials distribution had a better fitting in only ~5% of the species. Eukaryotic proteins have an average size of 472 aa, whereas bacterial (320 aa and archaeal (283 aa proteins are significantly smaller (33-40% on average. Average protein sizes in different phylogenetic groups were: Alveolata (628 aa, Amoebozoa (533 aa, Fornicata (543 aa, Placozoa (453 aa, Eumetazoa (486 aa, Fungi (487 aa, Stramenopila (486 aa, Viridiplantae (392 aa. Amino acid composition is biased according to protein size. Protein length correlated negatively with %C, %M, %K, %F, %R, %W, %Y and positively with %D, %E, %Q, %S and %T. Prokaryotic proteins had a different protein size bias for %E, %G, %K and %M as compared to eukaryotes. Conclusions Mathematical modeling of protein length empirical distributions can be used to asses the quality of small ORFs annotation in genomic releases (detection of too many false positive small ORFs. There is a negative correlation between average protein size and total number of

  8. Canine CNGA3 Gene Mutations Provide Novel Insights into Human Achromatopsia-Associated Channelopathies and Treatment.

    Directory of Open Access Journals (Sweden)

    Naoto Tanaka

    Full Text Available Cyclic nucleotide-gated (CNG ion channels are key mediators underlying signal transduction in retinal and olfactory receptors. Genetic defects in CNGA3 and CNGB3, encoding two structurally related subunits of cone CNG channels, lead to achromatopsia (ACHM. ACHM is a congenital, autosomal recessive retinal disorder that manifests by cone photoreceptor dysfunction, severely reduced visual acuity, impaired or complete color blindness and photophobia. Here, we report the first canine models for CNGA3-associated channelopathy caused by R424W or V644del mutations in the canine CNGA3 ortholog that accurately mimic the clinical and molecular features of human CNGA3-associated ACHM. These two spontaneous mutations exposed CNGA3 residues essential for the preservation of channel function and biogenesis. The CNGA3-R424W results in complete loss of cone function in vivo and channel activity confirmed by in vitro electrophysiology. Structural modeling and molecular dynamics (MD simulations revealed R424-E306 salt bridge formation and its disruption with the R424W mutant. Reversal of charges in a CNGA3-R424E-E306R double mutant channel rescued cGMP-activated currents uncovering new insights into channel gating. The CNGA3-V644del affects the C-terminal leucine zipper (CLZ domain destabilizing intersubunit interactions of the coiled-coil complex in the MD simulations; the in vitro experiments showed incompetent trimeric CNGA3 subunit assembly consistent with abnormal biogenesis of in vivo channels. These newly characterized large animal models not only provide a valuable system for studying cone-specific CNG channel function in health and disease, but also represent prime candidates for proof-of-concept studies of CNGA3 gene replacement therapy for ACHM patients.

  9. Hybrid discrete choice models: Gained insights versus increasing effort

    International Nuclear Information System (INIS)

    Mariel, Petr; Meyerhoff, Jürgen

    2016-01-01

    Hybrid choice models expand the standard models in discrete choice modelling by incorporating psychological factors as latent variables. They could therefore provide further insights into choice processes and underlying taste heterogeneity but the costs of estimating these models often significantly increase. This paper aims at comparing the results from a hybrid choice model and a classical random parameter logit. Point of departure for this analysis is whether researchers and practitioners should add hybrid choice models to their suite of models routinely estimated. Our comparison reveals, in line with the few prior studies, that hybrid models gain in efficiency by the inclusion of additional information. The use of one of the two proposed approaches, however, depends on the objective of the analysis. If disentangling preference heterogeneity is most important, hybrid model seems to be preferable. If the focus is on predictive power, a standard random parameter logit model might be the better choice. Finally, we give recommendations for an adequate use of hybrid choice models based on known principles of elementary scientific inference. - Highlights: • The paper compares performance of a Hybrid Choice Model (HCM) and a classical Random Parameter Logit (RPL) model. • The HCM indeed provides insights regarding preference heterogeneity not gained from the RPL. • The RPL has similar predictive power as the HCM in our data. • The costs of estimating HCM seem to be justified when learning more on taste heterogeneity is a major study objective.

  10. Hybrid discrete choice models: Gained insights versus increasing effort

    Energy Technology Data Exchange (ETDEWEB)

    Mariel, Petr, E-mail: petr.mariel@ehu.es [UPV/EHU, Economía Aplicada III, Avda. Lehendakari Aguire, 83, 48015 Bilbao (Spain); Meyerhoff, Jürgen [Institute for Landscape Architecture and Environmental Planning, Technical University of Berlin, D-10623 Berlin, Germany and The Kiel Institute for the World Economy, Duesternbrooker Weg 120, 24105 Kiel (Germany)

    2016-10-15

    Hybrid choice models expand the standard models in discrete choice modelling by incorporating psychological factors as latent variables. They could therefore provide further insights into choice processes and underlying taste heterogeneity but the costs of estimating these models often significantly increase. This paper aims at comparing the results from a hybrid choice model and a classical random parameter logit. Point of departure for this analysis is whether researchers and practitioners should add hybrid choice models to their suite of models routinely estimated. Our comparison reveals, in line with the few prior studies, that hybrid models gain in efficiency by the inclusion of additional information. The use of one of the two proposed approaches, however, depends on the objective of the analysis. If disentangling preference heterogeneity is most important, hybrid model seems to be preferable. If the focus is on predictive power, a standard random parameter logit model might be the better choice. Finally, we give recommendations for an adequate use of hybrid choice models based on known principles of elementary scientific inference. - Highlights: • The paper compares performance of a Hybrid Choice Model (HCM) and a classical Random Parameter Logit (RPL) model. • The HCM indeed provides insights regarding preference heterogeneity not gained from the RPL. • The RPL has similar predictive power as the HCM in our data. • The costs of estimating HCM seem to be justified when learning more on taste heterogeneity is a major study objective.

  11. Do flood risk perceptions provide useful insights for flood risk management? Findings from central Vietnam

    OpenAIRE

    Bubeck, P.; Botzen, W.J.W.; Suu, L.T.T.; Aerts, J.C.J.H.

    2012-01-01

    Following the renewed attention for non-structural flood risk reduction measures implemented at the household level, there has been an increased interest in individual flood risk perceptions. The reason for this is the commonly-made assumption that flood risk perceptions drive the motivation of individuals to undertake flood risk mitigation measures, as well as the public's demand for flood protection, and therefore provide useful insights for flood risk management. This study empirically exa...

  12. Newly evolved introns in human retrogenes provide novel insights into their evolutionary roles

    Directory of Open Access Journals (Sweden)

    Kang Li-Fang

    2012-07-01

    Full Text Available Abstract Background Retrogenes generally do not contain introns. However, in some instances, retrogenes may recruit internal exonic sequences as introns, which is known as intronization. A retrogene that undergoes intronization is a good model with which to investigate the origin of introns. Nevertheless, previously, only two cases in vertebrates have been reported. Results In this study, we systematically screened the human (Homo sapiens genome for retrogenes that evolved introns and analyzed their patterns in structure, expression and origin. In total, we identified nine intron-containing retrogenes. Alignment of pairs of retrogenes and their parents indicated that, in addition to intronization (five cases, retrogenes also may have gained introns by insertion of external sequences into the genes (one case or reversal of the orientation of transcription (three cases. Interestingly, many intronizations were promoted not by base substitutions but by cryptic splice sites, which were silent in the parental genes but active in the retrogenes. We also observed that the majority of introns generated by intronization did not involve frameshifts. Conclusions Intron gains in retrogenes are not as rare as previously thought. Furthermore, diverse mechanisms may lead to intron creation in retrogenes. The activation of cryptic splice sites in the intronization of retrogenes may be triggered by the change of gene structure after retroposition. A high percentage of non-frameshift introns in retrogenes may be because non-frameshift introns do not dramatically affect host proteins. Introns generated by intronization in human retrogenes are generally young, which is consistent with previous findings for Caenorhabditis elegans. Our results provide novel insights into the evolutionary role of introns.

  13. Development of Model for Providing Feasible Scholarship

    Directory of Open Access Journals (Sweden)

    Harry Dhika

    2016-05-01

    Full Text Available The current work focuses on the development of a model to determine a feasible scholarship recipient on the basis of the naiv¨e Bayes’ method using very simple and limited attributes. Those attributes are the applicants academic year, represented by their semester, academic performance, represented by their GPa, socioeconomic ability, which represented the economic capability to attend a higher education institution, and their level of social involvement. To establish and evaluate the model performance, empirical data are collected, and the data of 100 students are divided into 80 student data for the model training and the remaining of 20 student data are for the model testing. The results suggest that the model is capable to provide recommendations for the potential scholarship recipient at the level of accuracy of 95%.

  14. Insights provided by Probabilistic Safety Assessment Relating to the Loss of Electrical Sources

    International Nuclear Information System (INIS)

    Lanore, Jeanne-Marie

    2015-01-01

    The loss of electrical sources is generally an important contributor to the risk related to nuclear plants. In particular the external hazards initiating events lead generally to a loss of electrical sources. This importance was underscored by the Fukushima accident. A strength of PSA is to provide insights not only into the causes of the event but also into the potential consequences (core damage prevention, large release prevention, and mitigation) with the corresponding risk impact. PSA could provide a measure of Defence-in-Depth in case of loss of a safety function. The task intends to illustrate the PSA capabilities with outstanding practical examples. The task will rely on a survey of existing PSAs. It will provide a complementary view for ROBELSYS task. The content and status of the task are summarized in 2 slides

  15. Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution

    Science.gov (United States)

    Smith, Jeramiah J; Kuraku, Shigehiro; Holt, Carson; Sauka-Spengler, Tatjana; Jiang, Ning; Campbell, Michael S; Yandell, Mark D; Manousaki, Tereza; Meyer, Axel; Bloom, Ona E; Morgan, Jennifer R; Buxbaum, Joseph D; Sachidanandam, Ravi; Sims, Carrie; Garruss, Alexander S; Cook, Malcolm; Krumlauf, Robb; Wiedemann, Leanne M; Sower, Stacia A; Decatur, Wayne A; Hall, Jeffrey A; Amemiya, Chris T; Saha, Nil R; Buckley, Katherine M; Rast, Jonathan P; Das, Sabyasachi; Hirano, Masayuki; McCurley, Nathanael; Guo, Peng; Rohner, Nicolas; Tabin, Clifford J; Piccinelli, Paul; Elgar, Greg; Ruffier, Magali; Aken, Bronwen L; Searle, Stephen MJ; Muffato, Matthieu; Pignatelli, Miguel; Herrero, Javier; Jones, Matthew; Brown, C Titus; Chung-Davidson, Yu-Wen; Nanlohy, Kaben G; Libants, Scot V; Yeh, Chu-Yin; McCauley, David W; Langeland, James A; Pancer, Zeev; Fritzsch, Bernd; de Jong, Pieter J; Zhu, Baoli; Fulton, Lucinda L; Theising, Brenda; Flicek, Paul; Bronner, Marianne E; Warren, Wesley C; Clifton, Sandra W; Wilson, Richard K; Li, Weiming

    2013-01-01

    Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ~500 million years ago. By virtue of this deeply shared ancestry, the sea lamprey (P. marinus) genome is uniquely poised to provide insight into the ancestry of vertebrate genomes and the underlying principles of vertebrate biology. Here, we present the first lamprey whole-genome sequence and assembly. We note challenges faced owing to its high content of repetitive elements and GC bases, as well as the absence of broad-scale sequence information from closely related species. Analyses of the assembly indicate that two whole-genome duplications likely occurred before the divergence of ancestral lamprey and gnathostome lineages. Moreover, the results help define key evolutionary events within vertebrate lineages, including the origin of myelin-associated proteins and the development of appendages. The lamprey genome provides an important resource for reconstructing vertebrate origins and the evolutionary events that have shaped the genomes of extant organisms. PMID:23435085

  16. Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Atsushi Takata

    2018-01-01

    Full Text Available Recent studies have established important roles of de novo mutations (DNMs in autism spectrum disorders (ASDs. Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the “de novo paradigm” of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244 and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits. Analysis of individual genes identified 61 genes enriched for damaging DNMs, including ten genes for which our dataset now contributes to statistical significance. Screening of compounds altering the expression of genes hit by damaging DNMs reveals a global downregulating effect of valproic acid, a known risk factor for ASDs, whereas cardiac glycosides upregulate these genes. Collectively, our integrative approach provides deeper biological and potential medical insights into ASDs.

  17. Complementation studies with the novel "Bungowannah" virus provide new insights in the compatibility of pestivirus proteins.

    Science.gov (United States)

    Richter, Maria; Reimann, Ilona; Wegelt, Anne; Kirkland, Peter D; Beer, Martin

    2011-09-30

    In recent years several atypical pestiviruses have been described. Bungowannah virus is the most divergent virus in this group. Therefore, heterologous complementation was used to clarify the phylogenetic relationship and to analyze the exchangeability of genome regions encoding structural proteins. Using a BVDV type 1 backbone, chimeric constructs with substituted envelope proteins E(rns), E1 and E2, were investigated. While all constructs replicated autonomously, infectious high titer chimeric virus could only be observed after exchanging the complete E1-E2 encoding region. The complementation of E1 and E2 alone resulted only in replicons. Complementation of BVDV-E(rns) was only efficient if Bungowannah virus-E(rns) was expressed from a bicistronic construct. Our data provide new insights in the compatibility of pestivirus proteins and demonstrate that heterologous complementation could be useful to characterize new pestiviruses. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Whole genome analysis of Leptospira licerasiae provides insight into leptospiral evolution and pathogenicity.

    Directory of Open Access Journals (Sweden)

    Jessica N Ricaldi

    Full Text Available The whole genome analysis of two strains of the first intermediately pathogenic leptospiral species to be sequenced (Leptospira licerasiae strains VAR010 and MMD0835 provides insight into their pathogenic potential and deepens our understanding of leptospiral evolution. Comparative analysis of eight leptospiral genomes shows the existence of a core leptospiral genome comprising 1547 genes and 452 conserved genes restricted to infectious species (including L. licerasiae that are likely to be pathogenicity-related. Comparisons of the functional content of the genomes suggests that L. licerasiae retains several proteins related to nitrogen, amino acid and carbohydrate metabolism which might help to explain why these Leptospira grow well in artificial media compared with pathogenic species. L. licerasiae strains VAR010(T and MMD0835 possess two prophage elements. While one element is circular and shares homology with LE1 of L. biflexa, the second is cryptic and homologous to a previously identified but unnamed region in L. interrogans serovars Copenhageni and Lai. We also report a unique O-antigen locus in L. licerasiae comprised of a 6-gene cluster that is unexpectedly short compared with L. interrogans in which analogous regions may include >90 such genes. Sequence homology searches suggest that these genes were acquired by lateral gene transfer (LGT. Furthermore, seven putative genomic islands ranging in size from 5 to 36 kb are present also suggestive of antecedent LGT. How Leptospira become naturally competent remains to be determined, but considering the phylogenetic origins of the genes comprising the O-antigen cluster and other putative laterally transferred genes, L. licerasiae must be able to exchange genetic material with non-invasive environmental bacteria. The data presented here demonstrate that L. licerasiae is genetically more closely related to pathogenic than to saprophytic Leptospira and provide insight into the genomic bases for

  19. Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA

    International Nuclear Information System (INIS)

    Sidhu, Navdeep S.; Schreiber, Kathrin; Pröpper, Kevin; Becker, Stefan; Usón, Isabel; Sheldrick, George M.; Gärtner, Jutta; Krätzner, Ralph; Steinfeld, Robert

    2014-01-01

    Mucopolysaccharidosis IIIA is a fatal neurodegenerative disease that typically manifests itself in childhood and is caused by mutations in the gene for the lysosomal enzyme sulfamidase. The first structure of this enzyme is presented, which provides insight into the molecular basis of disease-causing mutations, and the enzymatic mechanism is proposed. Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder

  20. Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA

    Energy Technology Data Exchange (ETDEWEB)

    Sidhu, Navdeep S. [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany); University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Schreiber, Kathrin [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany); Pröpper, Kevin [University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Becker, Stefan [Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany); Usón, Isabel [Instituto de Biologia Molecular de Barcelona (IBMB–CSIC), Barcelona Science Park, Baldiri Reixach 15, 08028 Barcelona (Spain); Institucio Catalana de Recerca i Estudis Avancats (ICREA), (Spain); Sheldrick, George M. [University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Gärtner, Jutta; Krätzner, Ralph, E-mail: rkraetz@gwdg.de; Steinfeld, Robert, E-mail: rkraetz@gwdg.de [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany)

    2014-05-01

    Mucopolysaccharidosis IIIA is a fatal neurodegenerative disease that typically manifests itself in childhood and is caused by mutations in the gene for the lysosomal enzyme sulfamidase. The first structure of this enzyme is presented, which provides insight into the molecular basis of disease-causing mutations, and the enzymatic mechanism is proposed. Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder.

  1. Conceptual Models of the Individual Public Service Provider

    DEFF Research Database (Denmark)

    Andersen, Lotte Bøgh; Pedersen, Lene Holm; Bhatti, Yosef

    are used to gain insight on the motivation of public service providers; namely principal-agent theory, self-determination theory and public service motivation theory. We situate the theoretical discussions in the context of public service providers being transferred to private organizations......Individual public service providers’ motivation can be conceptualized as either extrinsic, autonomous or prosocial, and the question is how we can best theoretically understand this complexity without losing too much coherence and parsimony. Drawing on Allison’s approach (1969), three perspectives...... theoretical – to develop a coherent model of individual public service providers – but the empirical illustration also contributes to our understanding of motivation in the context of public sector outsourcing....

  2. Hyper-dry conditions provide new insights into the cause of extreme floods after wildfire

    Science.gov (United States)

    Moody, John A.; Ebel, Brian A.

    2012-01-01

    A catastrophic wildfire in the foothills of the Rocky Mountains near Boulder, Colorado provided a unique opportunity to investigate soil conditions immediately after a wildfire and before alteration by rainfall. Measurements of near-surface (θ; and matric suction, ψ), rainfall, and wind velocity were started 8 days after the wildfire began. These measurements established that hyper-dryconditions (θ 3 cm-3; ψ > ~ 3 x 105 cm) existed and provided an in-situ retention curve for these conditions. These conditions exacerbate the effects of water repellency (natural and fire-induced) and limit the effectiveness of capillarity and gravity driven infiltration into fire-affected soils. The important consequence is that given hyper-dryconditions, the critical rewetting process before the first rain is restricted to the diffusion–adsorption of water-vapor. This process typically has a time scale of days to weeks (especially when the hydrologic effects of the ash layer are included) that is longer than the typical time scale (minutes to hours) of some rainstorms, such that under hyper-dryconditions essentially no rain infiltrates. The existence of hyper-dryconditions provides insight into why, frequently during the first rain storm after a wildfire, nearly all rainfall becomes runoff causing extremefloods and debris flows.

  3. Molecular fossils in modern genomes provide physiological and geochemical insights to the ancient earth (Invited)

    Science.gov (United States)

    Dupont, C.; Caetano-Anolles, G.

    2010-12-01

    The genomes of extant organisms are ultimately derived from ancient life, thus theoretically contain insight to ancient physiology, ecology, and environments. In particular, metalloenzymes may be particularly insightful. The fundamental chemistry of trace elements dictates the molecular speciation and reactivity both within cells and the environment at large. Using protein structure and comparative genomics, we elucidate several major influences this chemistry has had upon biology. All of life exhibits the same proteome size-dependent scaling for the number of metal-binding proteins within a proteome. This fundamental evolutionary constant shows that the selection of one element occurs at the exclusion of another, with the eschewal of Fe for Zn and Ca being a defining feature of eukaryotic pro- teomes. Early life lacked both the structures required to control intracellular metal concentrations and the metal-binding proteins that catalyze electron transport and redox transformations. The development of protein structures for metal homeostasis coincided with the emergence of metal-specific structures, which predomi- nantly bound metals abundant in the Archean ocean. Potentially, this promoted the diversification of emerging lineages of Archaea and Bacteria through the establishment of biogeochemical cycles. In contrast, structures binding Cu and Zn evolved much later, pro- viding further evidence that environmental availability influenced the selection of the elements. The late evolving Zn-binding proteins are fundamental to eukaryotic cellular biology, and Zn bioavailabil- ity may have been a limiting factor in eukaryotic evolution. The results presented here provide an evolutionary timeline based on genomic characteristics, and key hypotheses can be tested by alternative geochemical methods.

  4. Tackling wicked problems: how theories of agency can provide new insights.

    Science.gov (United States)

    Varpio, Lara; Aschenbrener, Carol; Bates, Joanna

    2017-04-01

    This paper reviews why and how theories of agency can be used as analytical lenses to help health professions education (HPE) scholars address our community's wicked problems. Wicked problems are those that resist clear problem statements, defy traditional analysis approaches, and refuse definitive resolution (e.g. student remediation, assessments of professionalism, etc.). We illustrate how theories of agency can provide new insights into such challenges by examining the application of these theories to one particular wicked problem in HPE: interprofessional education (IPE). After searching the HPE literature and finding that theories of agency had received little attention, we borrowed techniques from narrative literature reviews to search databases indexing a broad scope of disciplines (i.e. ERIC, Web of Science, Scopus, MEDLINE and PubMed) for publications (1994-2014) that: (i) examined agency, or (ii) incorporated an agency-informed analytical perspective. The lead author identified the theories of agency used in these articles, and reviewed the texts on agency cited therein and the original sources of each theory. We identified 10 theories of agency that we considered to be applicable to HPE's wicked problems. To select a subset of theories for presentation in this paper, we discussed each theory in relation to some of HPE's wicked problems. Through debate and reflection, we unanimously agreed on the applicability of a subset of theories for illuminating HPE's wicked problems. This subset is described in this paper. We present four theories of agency: Butler's post-structural formulation; Giddens' sociological formulation; cultural historical activity theory's formulation, and Bandura's social cognitive psychology formulation. We introduce each theory and apply each to the challenges of engaging in IPE. Theories of agency can inform HPE scholarship in novel and generative ways. Each theory offers new insights into the roots of wicked problems and means for

  5. New technologies provide insights into genetic basis of psychiatric disorders and explain their co-morbidity.

    Science.gov (United States)

    Rudan, Igor

    2010-06-01

    The completion of Human Genome Project and the "HapMap" project was followed by translational activities from companies within the private sector. This led to the introduction of genome-wide scans based on hundreds of thousands of single nucleotide polymorphysms (SNP). These scans were based on common genetic variants in human populations. This new and powerful technology was then applied to the existing DNA-based datasets with information on psychiatric disorders. As a result, an unprecedented amount of novel scientific insights related to the underlying biology and genetics of psychiatric disorders was obtained. The dominant design of these studies, so called "genome-wide association studies" (GWAS), used statistical methods which minimized the risk of false positive reports and provided much greater power to detect genotype-phenotype associations. All findings were entirely data-driven rather than hypothesis-driven, which often made it difficult for researchers to understand or interpret the findings. Interestingly, this work in genetics is indicating how non-specific some genes are for psychiatric disorders, having associations in common for schizophrenia, bipolar disorder and autism. This suggests that the earlier stages of psychiatric disorders may be multi-valent and that early detection, coupled with a clearer understanding of the environmental factors, may allow prevention. At the present time, the rich "harvest" from GWAS still has very limited power to predict the variation in psychiatric disease status at individual level, typically explaining less than 5% of the total risk variance. The most recent studies of common genetic variation implicated the role of major histocompatibility complex in schizophrenia and other disorders. They also provided molecular evidence for a substantial polygenic component to the risk of psychiatric diseases, involving thousands of common alleles of very small effect. The studies of structural genetic variation, such as copy

  6. Cost Calculation Model for Logistics Service Providers

    Directory of Open Access Journals (Sweden)

    Zoltán Bokor

    2012-11-01

    Full Text Available The exact calculation of logistics costs has become a real challenge in logistics and supply chain management. It is essential to gain reliable and accurate costing information to attain efficient resource allocation within the logistics service provider companies. Traditional costing approaches, however, may not be sufficient to reach this aim in case of complex and heterogeneous logistics service structures. So this paper intends to explore the ways of improving the cost calculation regimes of logistics service providers and show how to adopt the multi-level full cost allocation technique in logistics practice. After determining the methodological framework, a sample cost calculation scheme is developed and tested by using estimated input data. Based on the theoretical findings and the experiences of the pilot project it can be concluded that the improved costing model contributes to making logistics costing more accurate and transparent. Moreover, the relations between costs and performances also become more visible, which enhances the effectiveness of logistics planning and controlling significantly

  7. The sea cucumber genome provides insights into morphological evolution and visceral regeneration.

    Science.gov (United States)

    Zhang, Xiaojun; Sun, Lina; Yuan, Jianbo; Sun, Yamin; Gao, Yi; Zhang, Libin; Li, Shihao; Dai, Hui; Hamel, Jean-François; Liu, Chengzhang; Yu, Yang; Liu, Shilin; Lin, Wenchao; Guo, Kaimin; Jin, Songjun; Xu, Peng; Storey, Kenneth B; Huan, Pin; Zhang, Tao; Zhou, Yi; Zhang, Jiquan; Lin, Chenggang; Li, Xiaoni; Xing, Lili; Huo, Da; Sun, Mingzhe; Wang, Lei; Mercier, Annie; Li, Fuhua; Yang, Hongsheng; Xiang, Jianhai

    2017-10-01

    Apart from sharing common ancestry with chordates, sea cucumbers exhibit a unique morphology and exceptional regenerative capacity. Here we present the complete genome sequence of an economically important sea cucumber, A. japonicus, generated using Illumina and PacBio platforms, to achieve an assembly of approximately 805 Mb (contig N50 of 190 Kb and scaffold N50 of 486 Kb), with 30,350 protein-coding genes and high continuity. We used this resource to explore key genetic mechanisms behind the unique biological characters of sea cucumbers. Phylogenetic and comparative genomic analyses revealed the presence of marker genes associated with notochord and gill slits, suggesting that these chordate features were present in ancestral echinoderms. The unique shape and weak mineralization of the sea cucumber adult body were also preliminarily explained by the contraction of biomineralization genes. Genome, transcriptome, and proteome analyses of organ regrowth after induced evisceration provided insight into the molecular underpinnings of visceral regeneration, including a specific tandem-duplicated prostatic secretory protein of 94 amino acids (PSP94)-like gene family and a significantly expanded fibrinogen-related protein (FREP) gene family. This high-quality genome resource will provide a useful framework for future research into biological processes and evolution in deuterostomes, including remarkable regenerative abilities that could have medical applications. Moreover, the multiomics data will be of prime value for commercial sea cucumber breeding programs.

  8. Dynamic transcriptional profiling provides insights into tuberous root development in Rehmannia glutinosa

    Directory of Open Access Journals (Sweden)

    Peng eSun

    2015-06-01

    Full Text Available Rehmannia glutinosa, a herb of the Scrophulariaceae family, is widely cultivated in the Northern part of China. The tuberous root has well known medicinal properties; however, yield and quality are threatened by abiotic and biotic stresses. Understanding the molecular process of tuberous root development may help identify novel targets for its control. In the present study, we used Illumina sequencing and de novo assembly strategies to obtain a reference transcriptome that is relevant to tuberous root development. We then conducted RNA-seq quantification analysis to determine gene expression profiles of the adventitious root (AR, thickening adventitious root (TAR, and the developing tuberous root (DTR. Expression profiling identified a total of 6,974 differentially expressed unigenes during root developmental. Bioinformatics analysis and gene expression profiling revealed changes in phenylpropanoid biosynthesis, starch and sucrose metabolism, and plant hormone biosynthesis during root development. Moreover, we identified and allocated putative functions to the genes involved in tuberous root development, including genes related to major carbohydrate metabolism, hormone metabolism, and transcription regulation. The present study provides the initial description of gene expression profiles of AR, TAR, and DTR, which facilitates identification of genes of interest. Moreover, our work provides insights into the molecular mechanisms underlying tuberous root development and may assist in the design and development of improved breeding schemes for different R. glutinosa varieties through genetic manipulation.

  9. The sea cucumber genome provides insights into morphological evolution and visceral regeneration.

    Directory of Open Access Journals (Sweden)

    Xiaojun Zhang

    2017-10-01

    Full Text Available Apart from sharing common ancestry with chordates, sea cucumbers exhibit a unique morphology and exceptional regenerative capacity. Here we present the complete genome sequence of an economically important sea cucumber, A. japonicus, generated using Illumina and PacBio platforms, to achieve an assembly of approximately 805 Mb (contig N50 of 190 Kb and scaffold N50 of 486 Kb, with 30,350 protein-coding genes and high continuity. We used this resource to explore key genetic mechanisms behind the unique biological characters of sea cucumbers. Phylogenetic and comparative genomic analyses revealed the presence of marker genes associated with notochord and gill slits, suggesting that these chordate features were present in ancestral echinoderms. The unique shape and weak mineralization of the sea cucumber adult body were also preliminarily explained by the contraction of biomineralization genes. Genome, transcriptome, and proteome analyses of organ regrowth after induced evisceration provided insight into the molecular underpinnings of visceral regeneration, including a specific tandem-duplicated prostatic secretory protein of 94 amino acids (PSP94-like gene family and a significantly expanded fibrinogen-related protein (FREP gene family. This high-quality genome resource will provide a useful framework for future research into biological processes and evolution in deuterostomes, including remarkable regenerative abilities that could have medical applications. Moreover, the multiomics data will be of prime value for commercial sea cucumber breeding programs.

  10. Transcriptome Analysis of Manganese-deficient Chlamydomonas reinhardtii Provides Insight on the Chlorophyll Biosynthesis Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lockhart, Ainsley; Zvenigorodsky, Natasha; Pedraza, Mary Ann; Lindquist, Erika

    2011-08-11

    The biosynthesis of chlorophyll and other tetrapyrroles is a vital but poorly understood process. Recent genomic advances with the unicellular green algae Chlamydomonas reinhardtii have created opportunity to more closely examine the mechanisms of the chlorophyll biosynthesis pathway via transcriptome analysis. Manganese is a nutrient of interest for complex reactions because of its multiple stable oxidation states and role in molecular oxygen coordination. C. reinhardtii was cultured in Manganese-deplete Tris-acetate-phosphate (TAP) media for 24 hours and used to create cDNA libraries for sequencing using Illumina TruSeq technology. Transcriptome analysis provided intriguing insight on possible regulatory mechanisms in the pathway. Evidence supports similarities of GTR (Glutamyl-tRNA synthase) to its Chlorella vulgaris homolog in terms of Mn requirements. Data was also suggestive of Mn-related compensatory up-regulation for pathway proteins CHLH1 (Manganese Chelatase), GUN4 (Magnesium chelatase activating protein), and POR1 (Light-dependent protochlorophyllide reductase). Intriguingly, data suggests possible reciprocal expression of oxygen dependent CPX1 (coproporphyrinogen III oxidase) and oxygen independent CPX2. Further analysis using RT-PCR could provide compelling evidence for several novel regulatory mechanisms in the chlorophyll biosynthesis pathway.

  11. Comparative transcriptome analysis provides new insights into erect and prostrate growth in bermudagrass (Cynodon dactylon L.).

    Science.gov (United States)

    Zhang, Bing; Xiao, Xiaolin; Zong, Junqin; Chen, Jingbo; Li, Jianjian; Guo, Hailin; Liu, Jianxiu

    2017-12-01

    Bermudagrass (Cynodon dactylon L.) is a prominent warm-season turf and forage grass species with multiple applications. In most C. dactylon cultivars and accessions, erect-growing stems (shoot) and prostrate-growing stems (stolon) often coexist. These two types of stems are both formed through tillering but grow in two directions with different tiller angles. Elucidating the mechanism of tiller angle regulation in bermudagrass could provide important clues to breed cultivars with different plant architectural features for diverse usage. In this study, we compared the stem internode transcriptome of two bermudagrass wild accessions with extremely different tiller angles and stem growth directions. A total of 2088 and 12,141 unigenes were preferentially expressed in prostrate-growing wild accession C792 and erect-growing wild accession C793, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology-based Annotation System (KOBAS) analyses further indicated that light- and gravity-responsive genes were enriched in accession C792, whereas lignin synthesis-related genes were enriched in accession C793, which well explains the difference in lignification of vascular bundles and mechanical tissues in the two accessions. These results not only expand our understanding of the genetic control of tiller angle and stem growth direction in bermudagrass but also provide insight for future molecular breeding of C. dactylon and other turfgrass species with different plant architectures. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. The pomegranate (Punica granatum L.) genome provides insights into fruit quality and ovule developmental biology.

    Science.gov (United States)

    Yuan, Zhaohe; Fang, Yanming; Zhang, Taikui; Fei, Zhangjun; Han, Fengming; Liu, Cuiyu; Liu, Min; Xiao, Wei; Zhang, Wenjing; Wu, Shan; Zhang, Mengwei; Ju, Youhui; Xu, Huili; Dai, He; Liu, Yujun; Chen, Yanhui; Wang, Lili; Zhou, Jianqing; Guan, Dian; Yan, Ming; Xia, Yanhua; Huang, Xianbin; Liu, Dongyuan; Wei, Hongmin; Zheng, Hongkun

    2017-12-22

    Pomegranate (Punica granatum L.) has an ancient cultivation history and has become an emerging profitable fruit crop due to its attractive features such as the bright red appearance and the high abundance of medicinally valuable ellagitannin-based compounds in its peel and aril. However, the limited genomic resources have restricted further elucidation of genetics and evolution of these interesting traits. Here, we report a 274-Mb high-quality draft pomegranate genome sequence, which covers approximately 81.5% of the estimated 336-Mb genome, consists of 2177 scaffolds with an N50 size of 1.7 Mb and contains 30 903 genes. Phylogenomic analysis supported that pomegranate belongs to the Lythraceae family rather than the monogeneric Punicaceae family, and comparative analyses showed that pomegranate and Eucalyptus grandis share the paleotetraploidy event. Integrated genomic and transcriptomic analyses provided insights into the molecular mechanisms underlying the biosynthesis of ellagitannin-based compounds, the colour formation in both peels and arils during pomegranate fruit development, and the unique ovule development processes that are characteristic of pomegranate. This genome sequence provides an important resource to expand our understanding of some unique biological processes and to facilitate both comparative biology studies and crop breeding. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  13. Insights into pre-reversal paleosecular variation from stochastic models

    Directory of Open Access Journals (Sweden)

    Klaudio ePeqini

    2015-09-01

    Full Text Available To provide insights on the paleosecular variation of the geomagnetic field and the mechanism of reversals, long time series of the dipolar magnetic moment are generated by two different stochastic models, known as the domino model and the inhomogeneous Lebovitz disk dynamo model, with initial values taken from the from paleomagnetic data. The former model considers mutual interactions of N macrospins embedded in a uniformly rotating medium, where random forcing and dissipation act on each macrospin. With an appropriate set of the model’s parameters values, the series generated by this model have similar statistical behaviour to the time series of the SHA.DIF.14K model. The latter model is an extension of the classical two-disk Rikitake model, considering N dynamo elements with appropriate interactions between them.We varied the parameters set of both models aiming at generating suitable time series with behaviour similar to the long time series of recent secular variation (SV. Such series are then extended to the near future, obtaining reversals in both cases of models. The analysis of the time series generated by simulating the models show that the reversals appears after a persistent period of low intensity geomagnetic field, as it is occurring in the present times.

  14. Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties.

    Science.gov (United States)

    Moreau, Christophe; Cioci, Gianluca; Iannello, Marina; Laffly, Emmanuelle; Chouquet, Anne; Ferreira, Arturo; Thielens, Nicole M; Gaboriaud, Christine

    2016-11-01

    Calreticulin (CRT) is a multifaceted protein, initially discovered as an endoplasmic reticulum (ER) chaperone protein, that is essential in calcium metabolism. Various implications in cancer, early development and immunology have been discovered more recently for CRT, as well as its role as a dominant 'eat-me' prophagocytic signal. Intriguingly, cell-surface exposure/secretion of CRT is among the infective strategies used by parasites such as Trypanosoma cruzi , Entamoeba histolytica , Taenia solium , Leishmania donovani and Schistosoma mansoni . Because of the inherent flexibility of CRTs, their analysis by X-ray crystallography requires the design of recombinant constructs suitable for crystallization, and thus only the structures of two very similar mammalian CRT lectin domains are known. With the X-ray structures of two distant parasite CRTs, insights into species structural determinants that might be harnessed to fight against the parasites without affecting the functions of the host CRT are now provided. Moreover, although the hypothesis that CRT can exhibit both open and closed conformations has been proposed in relation to its chaperone function, only the open conformation has so far been observed in crystal structures. The first evidence is now provided of a complex conformational transition with the junction reoriented towards P-domain closure. SAXS experiments also provided additional information about the flexibility of T. cruzi CRT in solution, thus complementing crystallographic data on the open conformation. Finally, regarding the conserved lectin-domain structure and chaperone function, evidence is provided of its dual carbohydrate/protein specificity and a new scheme is proposed to interpret such unusual substrate-binding properties. These fascinating features are fully consistent with previous experimental observations, as discussed considering the broad spectrum of CRT sequence conservations and differences.

  15. Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties

    Directory of Open Access Journals (Sweden)

    Christophe Moreau

    2016-11-01

    Full Text Available Calreticulin (CRT is a multifaceted protein, initially discovered as an endoplasmic reticulum (ER chaperone protein, that is essential in calcium metabolism. Various implications in cancer, early development and immunology have been discovered more recently for CRT, as well as its role as a dominant `eat-me' prophagocytic signal. Intriguingly, cell-surface exposure/secretion of CRT is among the infective strategies used by parasites such as Trypanosoma cruzi, Entamoeba histolytica, Taenia solium, Leishmania donovani and Schistosoma mansoni. Because of the inherent flexibility of CRTs, their analysis by X-ray crystallography requires the design of recombinant constructs suitable for crystallization, and thus only the structures of two very similar mammalian CRT lectin domains are known. With the X-ray structures of two distant parasite CRTs, insights into species structural determinants that might be harnessed to fight against the parasites without affecting the functions of the host CRT are now provided. Moreover, although the hypothesis that CRT can exhibit both open and closed conformations has been proposed in relation to its chaperone function, only the open conformation has so far been observed in crystal structures. The first evidence is now provided of a complex conformational transition with the junction reoriented towards P-domain closure. SAXS experiments also provided additional information about the flexibility of T. cruzi CRT in solution, thus complementing crystallographic data on the open conformation. Finally, regarding the conserved lectin-domain structure and chaperone function, evidence is provided of its dual carbohydrate/protein specificity and a new scheme is proposed to interpret such unusual substrate-binding properties. These fascinating features are fully consistent with previous experimental observations, as discussed considering the broad spectrum of CRT sequence conservations and differences.

  16. Comparison of the Internal Dynamics of Metalloproteases Provides New Insights on Their Function and Evolution.

    Directory of Open Access Journals (Sweden)

    Henrique F Carvalho

    Full Text Available Metalloproteases have evolved in a vast number of biological systems, being one of the most diverse types of proteases and presenting a wide range of folds and catalytic metal ions. Given the increasing understanding of protein internal dynamics and its role in enzyme function, we are interested in assessing how the structural heterogeneity of metalloproteases translates into their dynamics. Therefore, the dynamical profile of the clan MA type protein thermolysin, derived from an Elastic Network Model of protein structure, was evaluated against those obtained from a set of experimental structures and molecular dynamics simulation trajectories. A close correspondence was obtained between modes derived from the coarse-grained model and the subspace of functionally-relevant motions observed experimentally, the later being shown to be encoded in the internal dynamics of the protein. This prompted the use of dynamics-based comparison methods that employ such coarse-grained models in a representative set of clan members, allowing for its quantitative description in terms of structural and dynamical variability. Although members show structural similarity, they nonetheless present distinct dynamical profiles, with no apparent correlation between structural and dynamical relatedness. However, previously unnoticed dynamical similarity was found between the relevant members Carboxypeptidase Pfu, Leishmanolysin, and Botulinum Neurotoxin Type A, despite sharing no structural similarity. Inspection of the respective alignments shows that dynamical similarity has a functional basis, namely the need for maintaining proper intermolecular interactions with the respective substrates. These results suggest that distinct selective pressure mechanisms act on metalloproteases at structural and dynamical levels through the course of their evolution. This work shows how new insights on metalloprotease function and evolution can be assessed with comparison schemes that

  17. Obsessive compulsive disorder networks: positron emission tomography and neuropsychology provide new insights.

    Directory of Open Access Journals (Sweden)

    Bruno Millet

    Full Text Available BACKGROUND: Deep brain stimulation has shed new light on the central role of the prefrontal cortex (PFC in obsessive compulsive disorder (OCD. We explored this structure from a functional perspective, synchronizing neuroimaging and cognitive measures. METHODS AND FINDINGS: This case-control cross-sectional study compared 15 OCD patients without comorbidities and not currently on serotonin reuptake inhibitors or cognitive behavioural therapy with 15 healthy controls (matched for age, sex and education level on resting-state (18FDG-PET scans and a neuropsychological battery assessing executive functions. We looked for correlations between metabolic modifications and impaired neuropsychological scores. Modifications in glucose metabolism were found in frontal regions (orbitofrontal cortex and dorsolateral cortices, the cingulate gyrus, insula and parietal gyrus. Neuropsychological differences between patients and controls, which were subtle, were correlated with the metabolism of the prefrontal, parietal, and temporal cortices. CONCLUSION: As expected, we confirmed previous reports of a PFC dysfunction in OCD patients, and established a correlation with cognitive deficits. Other regions outside the prefrontal cortex, including the dorsoparietal cortex and the insula, also appeared to be implicated in the pathophysiology of OCD, providing fresh insights on the complexity of OCD syndromes.

  18. Obsessive Compulsive Disorder Networks: Positron Emission Tomography and Neuropsychology Provide New Insights

    Science.gov (United States)

    Millet, Bruno; Dondaine, Thibaut; Reymann, Jean-Michel; Bourguignon, Aurélie; Naudet, Florian; Jaafari, Nematollah; Drapier, Dominique; Turmel, Valérie; Mesbah, Habiba; Vérin, Marc; Le Jeune, Florence

    2013-01-01

    Background Deep brain stimulation has shed new light on the central role of the prefrontal cortex (PFC) in obsessive compulsive disorder (OCD). We explored this structure from a functional perspective, synchronizing neuroimaging and cognitive measures. Methods and Findings This case-control cross-sectional study compared 15 OCD patients without comorbidities and not currently on serotonin reuptake inhibitors or cognitive behavioural therapy with 15 healthy controls (matched for age, sex and education level) on resting-state 18FDG-PET scans and a neuropsychological battery assessing executive functions. We looked for correlations between metabolic modifications and impaired neuropsychological scores. Modifications in glucose metabolism were found in frontal regions (orbitofrontal cortex and dorsolateral cortices), the cingulate gyrus, insula and parietal gyrus. Neuropsychological differences between patients and controls, which were subtle, were correlated with the metabolism of the prefrontal, parietal, and temporal cortices. Conclusion As expected, we confirmed previous reports of a PFC dysfunction in OCD patients, and established a correlation with cognitive deficits. Other regions outside the prefrontal cortex, including the dorsoparietal cortex and the insula, also appeared to be implicated in the pathophysiology of OCD, providing fresh insights on the complexity of OCD syndromes. PMID:23326403

  19. Discovery of extremely halophilic, methyl-reducing euryarchaea provides insights into the evolutionary origin of methanogenesis

    Science.gov (United States)

    Sorokin, Dimitry Y.; Makarova, Kira S.; Abbas, Ben; Ferrer, Manuel; Golyshin, Peter N.; Galinski, Erwin A.; Ciordia, Sergio; Mena, María Carmen; Merkel, Alexander Y.; Wolf, Yuri I.; van Loosdrecht, Mark C.M.; Koonin, Eugene V.

    2017-01-01

    Methanogenic archaea are major players in the global carbon cycle and in the biotechnology of anaerobic digestion. The phylum Euryarchaeota includes diverse groups of methanogens that are interspersed with non-methanogenic lineages. So far methanogens inhabiting hypersaline environments have been identified only within the order Methanosarcinales. We report the discovery of a deep phylogenetic lineage of extremophilic methanogens in hypersaline lakes, and present analysis of two nearly complete genomes from this group. Within the phylum Euryarchaeota, these isolates form a separate, class-level lineage “Methanonatronarchaeia” that is most closely related to the class Halobacteria. Similar to the Halobacteria, “Methanonatronarchaeia” are extremely halophilic and do not accumulate organic osmoprotectants. The high intracellular concentration of potassium implies that “Methanonatronarchaeia” employ the “salt-in” osmoprotection strategy. These methanogens are heterotrophic methyl-reducers that utilize C1-methylated compounds as electron acceptors and formate or hydrogen as electron donors. The genomes contain an incomplete and apparently inactivated set of genes encoding the upper branch of methyl group oxidation to CO2 as well as membrane-bound heterosulfide reductase and cytochromes. These features differentiates “Methanonatronarchaeia” from all known methyl-reducing methanogens. The discovery of extremely halophilic, methyl-reducing methanogens related to haloarchaea provides insights into the origin of methanogenesis and shows that the strategies employed by methanogens to thrive in salt-saturating conditions are not limited to the classical methylotrophic pathway. PMID:28555626

  20. Metatranscriptome Analysis of Fig Flowers Provides Insights into Potential Mechanisms for Mutualism Stability and Gall Induction.

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    Ellen O Martinson

    Full Text Available A striking property of the mutualism between figs and their pollinating wasps is that wasps consistently oviposit in the inner flowers of the fig syconium, which develop into galls that house developing larvae. Wasps typically do not use the outer ring of flowers, which develop into seeds. To better understand differences between gall and seed flowers, we used a metatranscriptomic approach to analyze eukaryotic gene expression within fig flowers at the time of oviposition choice and early gall development. Consistent with the unbeatable seed hypothesis, we found significant differences in gene expression between gall- and seed flowers in receptive syconia prior to oviposition. In particular, transcripts assigned to flavonoids and carbohydrate metabolism were significantly up-regulated in gall flowers relative to seed flowers. In response to oviposition, gall flowers significantly up-regulated the expression of chalcone synthase, which previously has been connected to gall formation in other plants. We propose several genes encoding proteins with signal peptides or associations with venom of other Hymenoptera as candidate genes for gall initiation or growth. This study simultaneously evaluates the gene expression profile of both mutualistic partners in a plant-insect mutualism and provides insight into a possible stability mechanism in the ancient fig-fig wasp association.

  1. Comparative proteomic analysis provides insight into 10-hydroxy-2-decenoic acid biosynthesis in honey bee workers.

    Science.gov (United States)

    Yang, Xiao-Hui; Yang, Shi-Fa; Wang, Rui-Ming

    2017-07-01

    10-Hydroxy-2-decenoic acid (10-HDA) is the major compound produced from the mandibular glands (MGs) of honey bee workers. However, little information is available on the molecular mechanisms of 10-HDA biosynthesis. In our study, based on investigating the 10-HDA secretion pattern and the morphological characteristics of MGs from honey bee workers of different ages, a comparative proteomic analysis was performed in the MGs of workers with different 10-HDA production. In total, 59 up-regulated protein species representing 45 unique proteins were identified in high 10-HDA-producing workers by 2-DE-MALDI-TOF/TOF MS. These proteins were involved in carbohydrate/energy metabolism, fatty acid metabolism, protein metabolism and folding, antioxidation, cytoskeleton, development and cell signaling. Proteins related to fatty acid metabolism, including fatty acid synthase and β-oxidation enzymes, are potentially crucial proteins involved in 10-HDA biosynthesis pathway. And RNA interference (RNAi) results demonstrated that knockdown of electron transfer flavoprotein subunit beta (ETF-β), one of the protein related to fatty acid metabolism, decreased 10-HDA production of worker bees, suggesting that ETF-β was necessary for 10-HDA biosynthesis. This study reveals the characteristics of MGs of worker bees at different developmental stages and proteins associated with 10-HDA biosynthesis, which provides the first insight into the molecular mechanism of 10-HDA biosynthesis.

  2. Crystal structure of the Epithiospecifier Protein, ESP from Arabidopsis thaliana provides insights into its product specificity.

    Science.gov (United States)

    Zhang, Weiwei; Wang, Wenhe; Liu, Zihe; Xie, Yongchao; Wang, Hao; Mu, Yajuan; Huang, Yao; Feng, Yue

    2016-09-16

    Specifier proteins are important components of the glucosinolate-myrosinase system, which mediate plant defense against herbivory and pathogen attacks. Upon tissue disruption, glucosinolates are hydrolyzed to instable aglucones by myrosinases, and then aglucones will rearrange to form defensive isothiocyanates. Specifier proteins can redirect this reaction to form other products, such as simple nitriles, epithionitriles and organic thiocyanates instead of isothiocyanates based on the side chain structure of glucosinolate and the type of the specifier proteins. Nevertheless, the molecular mechanism underlying the different product spectrums of various specifier proteins was not fully understood. Here in this study, we solved the crystal structure of the Epithiospecifier Protein, ESP from Arabidopsis thaliana (AtESP) at 2.3 Å resolution. Structural comparisons with the previously solved structure of thiocyanate forming protein, TFP from Thlaspi arvense (TaTFP) reveal that AtESP shows a dimerization pattern different from TaTFP. Moreover, AtESP harbors a slightly larger active site pocket than TaTFP and several residues around the active site are different between the two proteins, which might account for the different product spectrums of the two proteins. Together, our structural study provides important insights into the molecular mechanisms of specifier proteins and shed light on the basis of their different product spectrums. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. A six-gene phylogeny provides new insights into choanoflagellate evolution.

    Science.gov (United States)

    Carr, Martin; Richter, Daniel J; Fozouni, Parinaz; Smith, Timothy J; Jeuck, Alexandra; Leadbeater, Barry S C; Nitsche, Frank

    2017-02-01

    Recent studies have shown that molecular phylogenies of the choanoflagellates (Class Choanoflagellatea) are in disagreement with their traditional taxonomy, based on morphology, and that Choanoflagellatea requires considerable taxonomic revision. Furthermore, phylogenies suggest that the morphological and ecological evolution of the group is more complex than has previously been recognized. Here we address the taxonomy of the major choanoflagellate order Craspedida, by erecting four new genera. The new genera are shown to be morphologically, ecologically and phylogenetically distinct from other choanoflagellate taxa. Furthermore, we name five novel craspedid species, as well as formally describe ten species that have been shown to be either misidentified or require taxonomic revision. Our revised phylogeny, including 18 new species and sequence data for two additional genes, provides insights into the morphological and ecological evolution of the choanoflagellates. We examine the distribution within choanoflagellates of these two additional genes, EF-1A and EFL, closely related translation GTPases which are required for protein synthesis. Mapping the presence and absence of these genes onto the phylogeny highlights multiple events of gene loss within the choanoflagellates. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Phylogenetic analyses provide insights into the historical biogeography and evolution of Brachyrhaphis fishes.

    Science.gov (United States)

    Ingley, Spencer J; Reina, Ruth G; Bermingham, Eldredge; Johnson, Jerald B

    2015-08-01

    The livebearing fish genus Brachyrhaphis (Poeciliidae) has become an increasingly important model in evolution and ecology research, yet the phylogeny of this group is not well understood, nor has it been examined thoroughly using modern phylogenetic methods. Here, we present the first comprehensive phylogenetic analysis of Brachyrhaphis by using four molecular markers (3mtDNA, 1nucDNA) to infer relationships among species in this genus. We tested the validity of this genus as a monophyletic group using extensive outgroup sampling based on recent phylogenetic hypotheses of Poeciliidae. We also tested the validity of recently described species of Brachyrhaphis that are part of the B. episcopi complex in Panama. Finally, we examined the impact of historical events on diversification of Brachyrhaphis, and made predictions regarding the role of different ecological environments on evolutionary diversification where known historical events apparently fail to explain speciation. Based on our results, we reject the monophyly of Brachyrhaphis, and question the validity of two recently described species (B. hessfeldi and B. roswithae). Historical biogeography of Brachyrhaphis generally agrees with patterns found in other freshwater taxa in Lower Central America, which show that geological barriers frequently predict speciation. Specifically, we find evidence in support of an 'island' model of Lower Central American formation, which posits that the nascent isthmus was partitioned by several marine connections before linking North and South America. In some cases where historic events (e.g., vicariance) fail to explain allopatric species breaks in Brachyrhaphis, ecological processes (e.g., divergent predation environments) offer additional insight into our understanding of phylogenetic diversification in this group. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Genome-wide investigation of transcription factors provides insights into transcriptional regulation in Plutella xylostella.

    Science.gov (United States)

    Zhao, Qian; Ma, Dongna; Huang, Yuping; He, Weiyi; Li, Yiying; Vasseur, Liette; You, Minsheng

    2018-04-01

    Transcription factors (TFs), which play a vital role in regulating gene expression, are prevalent in all organisms and characterization of them may provide important clues for understanding regulation in vivo. The present study reports a genome-wide investigation of TFs in the diamondback moth, Plutella xylostella (L.), a worldwide pest of crucifers. A total of 940 TFs distributed among 133 families were identified. Phylogenetic analysis of insect species showed that some of these families were found to have expanded during the evolution of P. xylostella or Lepidoptera. RNA-seq analysis showed that some of the TF families, such as zinc fingers, homeobox, bZIP, bHLH, and MADF_DNA_bdg genes, were highly expressed in certain tissues including midgut, salivary glands, fat body, and hemocytes, with an obvious sex-biased expression pattern. In addition, a number of TFs showed significant differences in expression between insecticide susceptible and resistant strains, suggesting that these TFs play a role in regulating genes related to insecticide resistance. Finally, we identified an expansion of the HOX cluster in Lepidoptera, which might be related to Lepidoptera-specific evolution. Knockout of this cluster using CRISPR/Cas9 showed that the egg cannot hatch, indicating that this cluster may be related to egg development and maturation. This is the first comprehensive study on identifying and characterizing TFs in P. xylostella. Our results suggest that some TF families are expanded in the P. xylostella genome, and these TFs may have important biological roles in growth, development, sexual dimorphism, and resistance to insecticides. The present work provides a solid foundation for understanding regulation via TFs in P. xylostella and insights into the evolution of the P. xylostella genome.

  6. Guide to Working with Model Providers.

    Science.gov (United States)

    Walter, Katie; Hassel, Bryan C.

    Often a central feature of a school's improvement efforts is the adoption of a Comprehensive School Reform (CSR) model, an externally developed research-based design for school improvement. Adopting a model is only the first step in CSR. Another important step is forging partnerships with developers of CSR models. This guide aims to help schools…

  7. A Representation for Gaining Insight into Clinical Decision Models

    Science.gov (United States)

    Jimison, Holly B.

    1988-01-01

    For many medical domains uncertainty and patient preferences are important components of decision making. Decision theory is useful as a representation for such medical models in computer decision aids, but the methodology has typically had poor performance in the areas of explanation and user interface. The additional representation of probabilities and utilities as random variables serves to provide a framework for graphical and text insight into complicated decision models. The approach allows for efficient customization of a generic model that describes the general patient population of interest to a patient- specific model. Monte Carlo simulation is used to calculate the expected value of information and sensitivity for each model variable, thus providing a metric for deciding what to emphasize in the graphics and text summary. The computer-generated explanation includes variables that are sensitive with respect to the decision or that deviate significantly from what is typically observed. These techniques serve to keep the assessment and explanation of the patient's decision model concise, allowing the user to focus on the most important aspects for that patient.

  8. On the Modelling of Biological Patterns with Mechanochemical Models: Insights from Analysis and Computation

    KAUST Repository

    Moreo, P.; Gaffney, E. A.; Garcí a-Aznar, J. M.; Doblaré , M.

    2009-01-01

    The diversity of biological form is generated by a relatively small number of underlying mechanisms. Consequently, mathematical and computational modelling can, and does, provide insight into how cellular level interactions ultimately give rise

  9. Measures of phylogenetic differentiation provide robust and complementary insights into microbial communities.

    Science.gov (United States)

    Parks, Donovan H; Beiko, Robert G

    2013-01-01

    High-throughput sequencing techniques have made large-scale spatial and temporal surveys of microbial communities routine. Gaining insight into microbial diversity requires methods for effectively analyzing and visualizing these extensive data sets. Phylogenetic β-diversity measures address this challenge by allowing the relationship between large numbers of environmental samples to be explored using standard multivariate analysis techniques. Despite the success and widespread use of phylogenetic β-diversity measures, an extensive comparative analysis of these measures has not been performed. Here, we compare 39 measures of phylogenetic β diversity in order to establish the relative similarity of these measures along with key properties and performance characteristics. While many measures are highly correlated, those commonly used within microbial ecology were found to be distinct from those popular within classical ecology, and from the recently recommended Gower and Canberra measures. Many of the measures are surprisingly robust to different rootings of the gene tree, the choice of similarity threshold used to define operational taxonomic units, and the presence of outlying basal lineages. Measures differ considerably in their sensitivity to rare organisms, and the effectiveness of measures can vary substantially under alternative models of differentiation. Consequently, the depth of sequencing required to reveal underlying patterns of relationships between environmental samples depends on the selected measure. Our results demonstrate that using complementary measures of phylogenetic β diversity can further our understanding of how communities are phylogenetically differentiated. Open-source software implementing the phylogenetic β-diversity measures evaluated in this manuscript is available at http://kiwi.cs.dal.ca/Software/ExpressBetaDiversity.

  10. Temperature-modulated DSC provides new insight about nickel-titanium wire transformations.

    Science.gov (United States)

    Brantley, William A; Iijima, Masahiro; Grentzer, Thomas H

    2003-10-01

    Differential scanning calorimetry (DSC) is a well-known method for investigating phase transformations in nickel-titanium orthodontic wires; the microstructural phases and phase transformations in these wires have central importance for their clinical performance. The purpose of this study was to use the more recently developed technique of temperature-modulated DSC (TMDSC) to gain insight into transformations in 3 nickel-titanium orthodontic wires: Neo Sentalloy (GAC International, Islandia, NY), 35 degrees C Copper Ni-Ti (Ormco, Glendora, Calif) and Nitinol SE (3M Unitek, Monrovia, Calif). In the oral environment, the first 2 superelastic wires have shape memory, and the third wire has superelastic behavior but not shape memory. All wires had cross-section dimensions of 0.016 x 0.022 in. Archwires in the as-received condition and after bending 135 degrees were cut into 5 or 6 segments for test specimens. TMDSC analyses (Model 2910 DSC, TA Instruments, Wilmington, Del) were conducted between -125 degrees C and 100 degrees C, using a linear heating and cooling rate of 2 degrees C per min, an oscillation amplitude of 0.318 degrees C with a period of 60 seconds, and helium as the purge gas. For all 3 wire alloys, strong low-temperature martensitic transformations, resolved on the nonreversing heat-flow curves, were not present on the reversing heat-flow curves, and bending appeared to increase the enthalpy change for these peaks in some cases. For Neo Sentalloy, TMDSC showed that transformation between martensitic and austenitic nickel-titanium, suggested as occurring directly in the forward and reverse directions by conventional DSC, was instead a 2-step process involving the R-phase. Two-step transformations in the forward and reverse directions were also found for 35 degrees C Copper Ni-Ti and Nitinol SE. The TMDSC results show that structural transformations in these wires are complex. Some possible clinical implications of these observations are discussed.

  11. Macroscale patterns in body size of intertidal crustaceans provide insights on climate change effects

    Science.gov (United States)

    Dugan, Jenifer E.; Hubbard, David M.; Contreras, Heraldo; Duarte, Cristian; Acuña, Emilio; Schoeman, David S.

    2017-01-01

    Predicting responses of coastal ecosystems to altered sea surface temperatures (SST) associated with global climate change, requires knowledge of demographic responses of individual species. Body size is an excellent metric because it scales strongly with growth and fecundity for many ectotherms. These attributes can underpin demographic as well as community and ecosystem level processes, providing valuable insights for responses of vulnerable coastal ecosystems to changing climate. We investigated contemporary macroscale patterns in body size among widely distributed crustaceans that comprise the majority of intertidal abundance and biomass of sandy beach ecosystems of the eastern Pacific coasts of Chile and California, USA. We focused on ecologically important species representing different tidal zones, trophic guilds and developmental modes, including a high-shore macroalga-consuming talitrid amphipod (Orchestoidea tuberculata), two mid-shore scavenging cirolanid isopods (Excirolana braziliensis and E. hirsuticauda), and a low-shore suspension-feeding hippid crab (Emerita analoga) with an amphitropical distribution. Significant latitudinal patterns in body sizes were observed for all species in Chile (21° - 42°S), with similar but steeper patterns in Emerita analoga, in California (32°- 41°N). Sea surface temperature was a strong predictor of body size (-4% to -35% °C-1) in all species. Beach characteristics were subsidiary predictors of body size. Alterations in ocean temperatures of even a few degrees associated with global climate change are likely to affect body sizes of important intertidal ectotherms, with consequences for population demography, life history, community structure, trophic interactions, food-webs, and indirect effects such as ecosystem function. The consistency of results for body size and temperature across species with different life histories, feeding modes, ecological roles, and microhabitats inhabiting a single widespread coastal

  12. Genome-wide analysis of Pax8 binding provides new insights into thyroid functions

    Directory of Open Access Journals (Sweden)

    Ruiz-Llorente Sergio

    2012-04-01

    Full Text Available Abstract Background The transcription factor Pax8 is essential for the differentiation of thyroid cells. However, there are few data on genes transcriptionally regulated by Pax8 other than thyroid-related genes. To better understand the role of Pax8 in the biology of thyroid cells, we obtained transcriptional profiles of Pax8-silenced PCCl3 thyroid cells using whole genome expression arrays and integrated these signals with global cis-regulatory sequencing studies performed by ChIP-Seq analysis Results Exhaustive analysis of Pax8 immunoprecipitated peaks demonstrated preferential binding to intragenic regions and CpG-enriched islands, which suggests a role of Pax8 in transcriptional regulation of orphan CpG regions. In addition, ChIP-Seq allowed us to identify Pax8 partners, including proteins involved in tertiary DNA structure (CTCF and chromatin remodeling (Sp1, and these direct transcriptional interactions were confirmed in vivo. Moreover, both factors modulate Pax8-dependent transcriptional activation of the sodium iodide symporter (Nis gene promoter. We ultimately combined putative and novel Pax8 binding sites with actual target gene expression regulation to define Pax8-dependent genes. Functional classification suggests that Pax8-regulated genes may be directly involved in important processes of thyroid cell function such as cell proliferation and differentiation, apoptosis, cell polarity, motion and adhesion, and a plethora of DNA/protein-related processes. Conclusion Our study provides novel insights into the role of Pax8 in thyroid biology, exerted through transcriptional regulation of important genes involved in critical thyrocyte processes. In addition, we found new transcriptional partners of Pax8, which functionally cooperate with Pax8 in the regulation of thyroid gene transcription. Besides, our data demonstrate preferential location of Pax8 in non-promoter CpG regions. These data point to an orphan CpG island-mediated mechanism

  13. Comparative proteomic analysis provides new insights into cadmium accumulation in rice grain under cadmium stress

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Dawei, E-mail: dwxue@hznu.edu.cn [College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036 (China); State Key Laboratory of Rice Biology, China National Rice Research Institute, Hangzhou 310006 (China); Jiang, Hua [State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Zhejiang Academy of Agricultural Science, Hangzhou 310021 (China); Deng, Xiangxiong; Zhang, Xiaoqin [College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036 (China); Wang, Hua [State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Zhejiang Academy of Agricultural Science, Hangzhou 310021 (China); Xu, Xiangbin [College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036 (China); Hu, Jiang; Zeng, Dali [State Key Laboratory of Rice Biology, China National Rice Research Institute, Hangzhou 310006 (China); Guo, Longbiao, E-mail: guolongbiao@caas.cn [State Key Laboratory of Rice Biology, China National Rice Research Institute, Hangzhou 310006 (China); Qian, Qian, E-mail: qianqian188@hotmail.com [College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036 (China); State Key Laboratory of Rice Biology, China National Rice Research Institute, Hangzhou 310006 (China)

    2014-09-15

    Graphical abstract: - Highlights: • Cd is the most toxic heavy metal and is a major pollutant in rice grains. • The mechanism of Cd accumulation in rice grains has not been well demonstrated. • Proteomics analysis is carried out and the verification is implemented by QPCR. • Proteins associated with ROS and photosynthesis showed large variation in expression. - Abstract: Rice is one of the most important staple crops. During the growth season, rice plants are inevitably subjected to numerous stresses, among which heavy metal stress represented by cadmium contamination not only hindering the yield of rice but also affecting the food safety by Cd accumulating in rice grains. The mechanism of Cd accumulation in rice grains has not been well elucidated. In this study, we compare the proteomic difference between two genotypes with different Cd accumulation ability in grains. Verification of differentially expressed protein-encoding genes was analyzing by quantitative PCR (QPCR) and reanalysis of microarray expression data. Forty-seven proteins in total were successfully identified through proteomic screening. GO and KEGG enrichment analysis showed Cd accumulation triggered stress-related pathways in the cells, and strongly affecting metabolic pathways. Many proteins associated with nutrient reservoir and starch-related enzyme were identified in this study suggesting that a considerably damage on grain quality was caused. The results also implied stress response was initiated by the abnormal cells and the transmission of signals may mediated by reactive oxygen species (ROS). Our research will provide new insights into Cd accumulation in rice grain under Cd stress.

  14. X-ray structure reveals a new class and provides insight into evolution of alkaline phosphatases.

    Directory of Open Access Journals (Sweden)

    Subhash C Bihani

    Full Text Available The alkaline phosphatase (AP is a bi-metalloenzyme of potential applications in biotechnology and bioremediation, in which phosphate monoesters are nonspecifically hydrolysed under alkaline conditions to yield inorganic phosphate. The hydrolysis occurs through an enzyme intermediate in which the catalytic residue is phosphorylated. The reaction, which also requires a third metal ion, is proposed to proceed through a mechanism of in-line displacement involving a trigonal bipyramidal transition state. Stabilizing the transition state by bidentate hydrogen bonding has been suggested to be the reason for conservation of an arginine residue in the active site. We report here the first crystal structure of alkaline phosphatase purified from the bacterium Sphingomonas. sp. Strain BSAR-1 (SPAP. The crystal structure reveals many differences from other APs: 1 the catalytic residue is a threonine instead of serine, 2 there is no third metal ion binding pocket, and 3 the arginine residue forming bidentate hydrogen bonding is deleted in SPAP. A lysine and an aspargine residue, recruited together for the first time into the active site, bind the substrate phosphoryl group in a manner not observed before in any other AP. These and other structural features suggest that SPAP represents a new class of APs. Because of its direct contact with the substrate phosphoryl group, the lysine residue is proposed to play a significant role in catalysis. The structure is consistent with a mechanism of in-line displacement via a trigonal bipyramidal transition state. The structure provides important insights into evolutionary relationships between members of AP superfamily.

  15. 3D-structured illumination microscopy provides novel insight into architecture of human centrosomes

    Directory of Open Access Journals (Sweden)

    Katharina F. Sonnen

    2012-08-01

    Centrioles are essential for the formation of cilia and flagella. They also form the core of the centrosome, which organizes microtubule arrays important for cell shape, polarity, motility and division. Here, we have used super-resolution 3D-structured illumination microscopy to analyse the spatial relationship of 18 centriole and pericentriolar matrix (PCM components of human centrosomes at different cell cycle stages. During mitosis, PCM proteins formed extended networks with interspersed γ-Tubulin. During interphase, most proteins were arranged at specific distances from the walls of centrioles, resulting in ring staining, often with discernible density masses. Through use of site-specific antibodies, we found the C-terminus of Cep152 to be closer to centrioles than the N-terminus, illustrating the power of 3D-SIM to study protein disposition. Appendage proteins showed rings with multiple density masses, and the number of these masses was strongly reduced during mitosis. At the proximal end of centrioles, Sas-6 formed a dot at the site of daughter centriole assembly, consistent with its role in cartwheel formation. Plk4 and STIL co-localized with Sas-6, but Cep135 was associated mostly with mother centrioles. Remarkably, Plk4 formed a dot on the surface of the mother centriole before Sas-6 staining became detectable, indicating that Plk4 constitutes an early marker for the site of nascent centriole formation. Our study provides novel insights into the architecture of human centrosomes and illustrates the power of super-resolution microscopy in revealing the relative localization of centriole and PCM proteins in unprecedented detail.

  16. Proteomic analysis of FUS interacting proteins provides insights into FUS function and its role in ALS.

    Science.gov (United States)

    Kamelgarn, Marisa; Chen, Jing; Kuang, Lisha; Arenas, Alexandra; Zhai, Jianjun; Zhu, Haining; Gal, Jozsef

    2016-10-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Mutations in the Fused in Sarcoma/Translocated in Liposarcoma (FUS/TLS) gene cause a subset of familial ALS cases and are also implicated in sporadic ALS. FUS is typically localized to the nucleus. The ALS-related FUS mutations cause cytoplasmic mis-localization and the formation of stress granule-like structures. Abnormal cytoplasmic FUS localization was also found in a subset of frontotemporal dementia (FTLD) cases without FUS mutations. To better understand the function of FUS, we performed wild-type and mutant FUS pull-downs followed by proteomic identification of the interacting proteins. The FUS interacting partners we identified are involved in multiple pathways, including chromosomal organization, transcription, RNA splicing, RNA transport, localized translation, and stress response. FUS interacted with hnRNPA1 and Matrin-3, RNA binding proteins whose mutations were also reported to cause familial ALS, suggesting that hnRNPA1 and Matrin-3 may play common pathogenic roles with FUS. The FUS interactions displayed varied RNA dependence. Numerous FUS interacting partners that we identified are components of exosomes. We found that FUS itself was present in exosomes, suggesting that the secretion of FUS might contribute to the cell-to-cell spreading of FUS pathology. FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. Our results provide insights into the physiological functions of FUS as well as important pathways where mutant FUS can interfere with cellular processes and potentially contribute to the pathogenesis of ALS. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. User experiences with clinical social franchising: qualitative insights from providers and clients in Ghana and Kenya

    OpenAIRE

    Sieverding, Maia; Briegleb, Christina; Montagu, Dominic

    2015-01-01

    Background Clinical social franchising is a rapidly growing delivery model in private healthcare markets in low- and middle-income countries. Despite this growth, little is known about providers? perceptions of the benefits and challenges of social franchising or clients? reasons for choosing franchised facilities over other healthcare options. We examine these questions in the context of three social franchise networks in Ghana and Kenya. Methods We conducted in-depth interviews with a purpo...

  18. Vitiligo blood transcriptomics provides new insights into disease mechanisms and identifies potential novel therapeutic targets.

    Science.gov (United States)

    Dey-Rao, Rama; Sinha, Animesh A

    2017-01-28

    Significant gaps remain regarding the pathomechanisms underlying the autoimmune response in vitiligo (VL), where the loss of self-tolerance leads to the targeted killing of melanocytes. Specifically, there is incomplete information regarding alterations in the systemic environment that are relevant to the disease state. We undertook a genome-wide profiling approach to examine gene expression in the peripheral blood of VL patients and healthy controls in the context of our previously published VL-skin gene expression profile. We used several in silico bioinformatics-based analyses to provide new insights into disease mechanisms and suggest novel targets for future therapy. Unsupervised clustering methods of the VL-blood dataset demonstrate a "disease-state"-specific set of co-expressed genes. Ontology enrichment analysis of 99 differentially expressed genes (DEGs) uncovers a down-regulated immune/inflammatory response, B-Cell antigen receptor (BCR) pathways, apoptosis and catabolic processes in VL-blood. There is evidence for both type I and II interferon (IFN) playing a role in VL pathogenesis. We used interactome analysis to identify several key blood associated transcriptional factors (TFs) from within (STAT1, STAT6 and NF-kB), as well as "hidden" (CREB1, MYC, IRF4, IRF1, and TP53) from the dataset that potentially affect disease pathogenesis. The TFs overlap with our reported lesional-skin transcriptional circuitry, underscoring their potential importance to the disease. We also identify a shared VL-blood and -skin transcriptional "hot spot" that maps to chromosome 6, and includes three VL-blood dysregulated genes (PSMB8, PSMB9 and TAP1) described as potential VL-associated genetic susceptibility loci. Finally, we provide bioinformatics-based support for prioritizing dysregulated genes in VL-blood or skin as potential therapeutic targets. We examined the VL-blood transcriptome in context with our (previously published) VL-skin transcriptional profile to address

  19. User experiences with clinical social franchising: qualitative insights from providers and clients in Ghana and Kenya.

    Science.gov (United States)

    Sieverding, Maia; Briegleb, Christina; Montagu, Dominic

    2015-02-01

    Clinical social franchising is a rapidly growing delivery model in private healthcare markets in low- and middle-income countries. Despite this growth, little is known about providers' perceptions of the benefits and challenges of social franchising or clients' reasons for choosing franchised facilities over other healthcare options. We examine these questions in the context of three social franchise networks in Ghana and Kenya. We conducted in-depth interviews with a purposive sample of providers from the BlueStar Ghana, and Amua and Tunza networks in Kenya. We also conducted qualitative exit interviews with female clients who were leaving franchised facilities after a visit for a reproductive or child health reason. The total sample consists of 47 providers and 47 clients across the three networks. Providers perceived the main benefits of participation in a social franchise network to be training opportunities and access to a consistent supply of low-cost family planning commodities; few providers mentioned branding as a benefit of participation. Although most providers said that client flows for franchised services increased after joining the network, they did not associate this with improved finances for their facility. Clients overwhelmingly cited the quality of the client-provider relationship as their main motivation for attending the franchise facility. Recognition of the franchise brand was low among clients who were exiting a franchised facility. The most important benefit of social franchise programs to both providers and their clients may have more to do with training on business practices, patient counseling and customer service, than with subsidies, technical input, branding or clinical support. This finding may lead to a reconsideration of how franchise programs interact with both their member clinics and the larger health-seeking communities they serve.

  20. Providing guidance for genomics-based cancer treatment decisions: insights from stakeholder engagement for post-prostatectomy radiation therapy.

    Science.gov (United States)

    Abe, James; Lobo, Jennifer M; Trifiletti, Daniel M; Showalter, Timothy N

    2017-08-24

    Despite the emergence of genomics-based risk prediction tools in oncology, there is not yet an established framework for communication of test results to cancer patients to support shared decision-making. We report findings from a stakeholder engagement program that aimed to develop a framework for using Markov models with individualized model inputs, including genomics-based estimates of cancer recurrence probability, to generate personalized decision aids for prostate cancer patients faced with radiation therapy treatment decisions after prostatectomy. We engaged a total of 22 stakeholders, including: prostate cancer patients, urological surgeons, radiation oncologists, genomic testing industry representatives, and biomedical informatics faculty. Slides were at each meeting to provide background information regarding the analytical framework. Participants were invited to provide feedback during the meeting, including revising the overall project aims. Stakeholder meeting content was reviewed and summarized by stakeholder group and by theme. The majority of stakeholder suggestions focused on aspects of decision aid design and formatting. Stakeholders were enthusiastic about the potential value of using decision analysis modeling with personalized model inputs for cancer recurrence risk, as well as competing risks from age and comorbidities, to generate a patient-centered tool to assist decision-making. Stakeholders did not view privacy considerations as a major barrier to the proposed decision aid program. A common theme was that decision aids should be portable across multiple platforms (electronic and paper), should allow for interaction by the user to adjust model inputs iteratively, and available to patients both before and during consult appointments. Emphasis was placed on the challenge of explaining the model's composite result of quality-adjusted life years. A range of stakeholders provided valuable insights regarding the design of a personalized decision

  1. Fluid mechanics in dentinal microtubules provides mechanistic insights into the difference between hot and cold dental pain.

    Science.gov (United States)

    Lin, Min; Luo, Zheng Yuan; Bai, Bo Feng; Xu, Feng; Lu, Tian Jian

    2011-03-23

    Dental thermal pain is a significant health problem in daily life and dentistry. There is a long-standing question regarding the phenomenon that cold stimulation evokes sharper and more shooting pain sensations than hot stimulation. This phenomenon, however, outlives the well-known hydrodynamic theory used to explain dental thermal pain mechanism. Here, we present a mathematical model based on the hypothesis that hot or cold stimulation-induced different directions of dentinal fluid flow and the corresponding odontoblast movements in dentinal microtubules contribute to different dental pain responses. We coupled a computational fluid dynamics model, describing the fluid mechanics in dentinal microtubules, with a modified Hodgkin-Huxley model, describing the discharge behavior of intradental neuron. The simulated results agreed well with existing experimental measurements. We thence demonstrated theoretically that intradental mechano-sensitive nociceptors are not "equally sensitive" to inward (into the pulp) and outward (away from the pulp) fluid flows, providing mechanistic insights into the difference between hot and cold dental pain. The model developed here could enable better diagnosis in endodontics which requires an understanding of pulpal histology, neurology and physiology, as well as their dynamic response to the thermal stimulation used in dental practices.

  2. Multiple Problem-Solving Strategies Provide Insight into Students' Understanding of Open-Ended Linear Programming Problems

    Science.gov (United States)

    Sole, Marla A.

    2016-01-01

    Open-ended questions that can be solved using different strategies help students learn and integrate content, and provide teachers with greater insights into students' unique capabilities and levels of understanding. This article provides a problem that was modified to allow for multiple approaches. Students tended to employ high-powered, complex,…

  3. Cholinergic modulation of cognitive processing: insights drawn from computational models

    Directory of Open Access Journals (Sweden)

    Ehren L Newman

    2012-06-01

    Full Text Available Acetylcholine plays an important role in cognitive function, as shown by pharmacological manipulations that impact working memory, attention, episodic memory and spatial memory function. Acetylcholine also shows striking modulatory influences on the cellular physiology of hippocampal and cortical neurons. Modeling of neural circuits provides a framework for understanding how the cognitive functions may arise from the influence of acetylcholine on neural and network dynamics. We review the influences of cholinergic manipulations on behavioral performance in working memory, attention, episodic memory and spatial memory tasks, the physiological effects of acetylcholine on neural and circuit dynamics, and the computational models that provide insight into the functional relationships between the physiology and behavior. Specifically, we discuss the important role of acetylcholine in governing mechanisms of active maintenance in working memory tasks and in regulating network dynamics important for effective processing of stimuli in attention and episodic memory tasks. We also propose that theta rhythm play a crucial role as an intermediary between the physiological influences of acetylcholine and behavior in episodic and spatial memory tasks. We conclude with a synthesis of the existing modeling work and highlight future directions that are likely to be rewarding given the existing state of the literature for both empiricists and modelers.

  4. Osteoarthritis: new insights in animal models.

    Science.gov (United States)

    Longo, Umile Giuseppe; Loppini, Mattia; Fumo, Caterina; Rizzello, Giacomo; Khan, Wasim Sardar; Maffulli, Nicola; Denaro, Vincenzo

    2012-01-01

    Osteoarthritis (OA) is the most frequent and symptomatic health problem in the middle-aged and elderly population, with over one-half of all people over the age of 65 showing radiographic changes in painful knees. The aim of the present study was to perform an overview on the available animal models used in the research field on the OA. Discrepancies between the animal models and the human disease are present. As regards human 'idiopathic' OA, with late onset and slow progression, it is perhaps wise not to be overly enthusiastic about animal models that show severe chondrodysplasia and very early OA. Advantage by using genetically engineered mouse models, in comparison with other surgically induced models, is that molecular etiology is known. Find potential molecular markers for the onset of the disease and pay attention to the role of gender and environmental factors should be very helpful in the study of mice that acquire premature OA. Surgically induced destabilization of joint is the most widely used induction method. These models allow the temporal control of disease induction and follow predictable progression of the disease. In animals, ACL transection and meniscectomy show a speed of onset and severity of disease higher than in humans after same injury.

  5. Mathematical model insights into arsenic detoxification

    Directory of Open Access Journals (Sweden)

    Nijhout H Frederik

    2011-08-01

    Full Text Available Abstract Background Arsenic in drinking water, a major health hazard to millions of people in South and East Asia and in other parts of the world, is ingested primarily as trivalent inorganic arsenic (iAs, which then undergoes hepatic methylation to methylarsonic acid (MMAs and a second methylation to dimethylarsinic acid (DMAs. Although MMAs and DMAs are also known to be toxic, DMAs is more easily excreted in the urine and therefore methylation has generally been considered a detoxification pathway. A collaborative modeling project between epidemiologists, biologists, and mathematicians has the purpose of explaining existing data on methylation in human studies in Bangladesh and also testing, by mathematical modeling, effects of nutritional supplements that could increase As methylation. Methods We develop a whole body mathematical model of arsenic metabolism including arsenic absorption, storage, methylation, and excretion. The parameters for arsenic methylation in the liver were taken from the biochemical literature. The transport parameters between compartments are largely unknown, so we adjust them so that the model accurately predicts the urine excretion rates of time for the iAs, MMAs, and DMAs in single dose experiments on human subjects. Results We test the model by showing that, with no changes in parameters, it predicts accurately the time courses of urinary excretion in mutiple dose experiments conducted on human subjects. Our main purpose is to use the model to study and interpret the data on the effects of folate supplementation on arsenic methylation and excretion in clinical trials in Bangladesh. Folate supplementation of folate-deficient individuals resulted in a 14% decrease in arsenicals in the blood. This is confirmed by the model and the model predicts that arsenicals in the liver will decrease by 19% and arsenicals in other body stores by 26% in these same individuals. In addition, the model predicts that arsenic

  6. New Insights from Rodent Models of Fatty Liver Disease

    Science.gov (United States)

    2011-01-01

    Abstract Rodent models of fatty liver disease are essential research tools that provide a window into disease pathogenesis and a testing ground for prevention and treatment. Models come in many varieties involving dietary and genetic manipulations, and sometimes both. High-energy diets that induce obesity do not uniformly cause fatty liver disease; this has prompted close scrutiny of specific macronutrients and nutrient combinations to determine which have the greatest potential for hepatotoxicity. At the same time, diets that do not cause obesity or the metabolic syndrome but do cause severe steatohepatitis have been exploited to study factors important to progressive liver injury, including cell death, oxidative stress, and immune activation. Rodents with a genetic predisposition to overeating offer yet another model in which to explore the evolution of fatty liver disease. In some animals that overeat, steatohepatitis can develop even without resorting to a high-energy diet. Importantly, these models and others have been used to document that aerobic exercise can prevent or reduce fatty liver disease. This review focuses primarily on lessons learned about steatohepatitis from manipulations of diet and eating behavior. Numerous additional insights about hepatic lipid metabolism, which have been gained from genetically engineered mice, are also mentioned. Antioxid. Redox Signal. 15, 535–550. PMID:21126212

  7. Melatonin receptors: latest insights from mouse models

    Science.gov (United States)

    Tosini, Gianluca; Owino, Sharon; Guillame, Jean-Luc; Jockers, Ralf

    2014-01-01

    Summary Melatonin, the neuro-hormone synthesized during the night, has recently seen an unexpected extension of its functional implications towards type 2 diabetes development, visual functions, sleep disturbances and depression. Transgenic mouse models were instrumental for the establishment of the link between melatonin and these major human diseases. Most of the actions of melatonin are mediated by two types of G protein-coupled receptors, named MT1 and MT2, which are expressed in many different organs and tissues. Understanding the pharmacology and function of mouse MT1 and MT2 receptors, including MT1/MT2 heteromers, will be of crucial importance to evaluate the relevance of these mouse models for future therapeutic developments. This review will critically discuss these aspects, and give some perspectives including the generation of new mouse models. PMID:24903552

  8. Osteoarthritis: New Insights in Animal Models

    OpenAIRE

    Longo, Umile Giuseppe; Loppini, Mattia; Fumo, Caterina; Rizzello, Giacomo; Khan, Wasim Sardar; Maffulli, Nicola; Denaro, Vincenzo

    2012-01-01

    Osteoarthritis (OA) is the most frequent and symptomatic health problem in the middle-aged and elderly population, with over one-half of all people over the age of 65 showing radiographic changes in painful knees. The aim of the present study was to perform an overview on the available animal models used in the research field on the OA. Discrepancies between the animal models and the human disease are present. As regards human ‘idiopathic’ OA, with late onset and slow progression, it is perha...

  9. The Rosa genome provides new insights into the domestication of modern roses.

    Science.gov (United States)

    Raymond, Olivier; Gouzy, Jérôme; Just, Jérémy; Badouin, Hélène; Verdenaud, Marion; Lemainque, Arnaud; Vergne, Philippe; Moja, Sandrine; Choisne, Nathalie; Pont, Caroline; Carrère, Sébastien; Caissard, Jean-Claude; Couloux, Arnaud; Cottret, Ludovic; Aury, Jean-Marc; Szécsi, Judit; Latrasse, David; Madoui, Mohammed-Amin; François, Léa; Fu, Xiaopeng; Yang, Shu-Hua; Dubois, Annick; Piola, Florence; Larrieu, Antoine; Perez, Magali; Labadie, Karine; Perrier, Lauriane; Govetto, Benjamin; Labrousse, Yoan; Villand, Priscilla; Bardoux, Claudia; Boltz, Véronique; Lopez-Roques, Céline; Heitzler, Pascal; Vernoux, Teva; Vandenbussche, Michiel; Quesneville, Hadi; Boualem, Adnane; Bendahmane, Abdelhafid; Liu, Chang; Le Bris, Manuel; Salse, Jérôme; Baudino, Sylvie; Benhamed, Moussa; Wincker, Patrick; Bendahmane, Mohammed

    2018-06-01

    Roses have high cultural and economic importance as ornamental plants and in the perfume industry. We report the rose whole-genome sequencing and assembly and resequencing of major genotypes that contributed to rose domestication. We generated a homozygous genotype from a heterozygous diploid modern rose progenitor, Rosa chinensis 'Old Blush'. Using single-molecule real-time sequencing and a meta-assembly approach, we obtained one of the most comprehensive plant genomes to date. Diversity analyses highlighted the mosaic origin of 'La France', one of the first hybrids combining the growth vigor of European species and the recurrent blooming of Chinese species. Genomic segments of Chinese ancestry identified new candidate genes for recurrent blooming. Reconstructing regulatory and secondary metabolism pathways allowed us to propose a model of interconnected regulation of scent and flower color. This genome provides a foundation for understanding the mechanisms governing rose traits and should accelerate improvement in roses, Rosaceae and ornamentals.

  10. Genomic and proteomic analyses of the fungus Arthrobotrys oligospora provide insights into nematode-trap formation.

    Science.gov (United States)

    Yang, Jinkui; Wang, Lei; Ji, Xinglai; Feng, Yun; Li, Xiaomin; Zou, Chenggang; Xu, Jianping; Ren, Yan; Mi, Qili; Wu, Junli; Liu, Shuqun; Liu, Yu; Huang, Xiaowei; Wang, Haiyan; Niu, Xuemei; Li, Juan; Liang, Lianming; Luo, Yanlu; Ji, Kaifang; Zhou, Wei; Yu, Zefen; Li, Guohong; Liu, Yajun; Li, Lei; Qiao, Min; Feng, Lu; Zhang, Ke-Qin

    2011-09-01

    Nematode-trapping fungi are "carnivorous" and attack their hosts using specialized trapping devices. The morphological development of these traps is the key indicator of their switch from saprophytic to predacious lifestyles. Here, the genome of the nematode-trapping fungus Arthrobotrys oligospora Fres. (ATCC24927) was reported. The genome contains 40.07 Mb assembled sequence with 11,479 predicted genes. Comparative analysis showed that A. oligospora shared many more genes with pathogenic fungi than with non-pathogenic fungi. Specifically, compared to several sequenced ascomycete fungi, the A. oligospora genome has a larger number of pathogenicity-related genes in the subtilisin, cellulase, cellobiohydrolase, and pectinesterase gene families. Searching against the pathogen-host interaction gene database identified 398 homologous genes involved in pathogenicity in other fungi. The analysis of repetitive sequences provided evidence for repeat-induced point mutations in A. oligospora. Proteomic and quantitative PCR (qPCR) analyses revealed that 90 genes were significantly up-regulated at the early stage of trap-formation by nematode extracts and most of these genes were involved in translation, amino acid metabolism, carbohydrate metabolism, cell wall and membrane biogenesis. Based on the combined genomic, proteomic and qPCR data, a model for the formation of nematode trapping device in this fungus was proposed. In this model, multiple fungal signal transduction pathways are activated by its nematode prey to further regulate downstream genes associated with diverse cellular processes such as energy metabolism, biosynthesis of the cell wall and adhesive proteins, cell division, glycerol accumulation and peroxisome biogenesis. This study will facilitate the identification of pathogenicity-related genes and provide a broad foundation for understanding the molecular and evolutionary mechanisms underlying fungi-nematodes interactions.

  11. Esophageal Cancer: Insights from Mouse Models

    Directory of Open Access Journals (Sweden)

    Marie-Pier Tétreault

    2015-01-01

    Full Text Available Esophageal cancer is the eighth leading cause of cancer and the sixth most common cause of cancer-related death worldwide. Despite recent advances in the development of surgical techniques in combination with the use of radiotherapy and chemotherapy, the prognosis for esophageal cancer remains poor. The cellular and molecular mechanisms that drive the pathogenesis of esophageal cancer are still poorly understood. Hence, understanding these mechanisms is crucial to improving outcomes for patients with esophageal cancer. Mouse models constitute valuable tools for modeling human cancers and for the preclinical testing of therapeutic strategies in a manner not possible in human subjects. Mice are excellent models for studying human cancers because they are similar to humans at the physiological and molecular levels and because they have a shorter gestation time and life cycle. Moreover, a wide range of well-developed technologies for introducing genetic modifications into mice are currently available. In this review, we describe how different mouse models are used to study esophageal cancer.

  12. Cancer immunotherapy : insights from transgenic animal models

    NARCIS (Netherlands)

    McLaughlin, PMJ; Kroesen, BJ; Harmsen, MC; de Leij, LFMH

    2001-01-01

    A wide range of strategies in cancer immunotherapy has been developed in the last decade, some of which are currently being used in clinical settings. The development of these immunotherapeutical strategies has been facilitated by the generation of relevant transgenic animal models. Since the

  13. A recovery principle provides insight into auxin pattern control in the Arabidopsis root

    Science.gov (United States)

    Moore, Simon; Liu, Junli; Zhang, Xiaoxian; Lindsey, Keith

    2017-01-01

    Regulated auxin patterning provides a key mechanism for controlling root growth and development. We have developed a data-driven mechanistic model using realistic root geometry and formulated a principle to theoretically investigate quantitative auxin pattern recovery following auxin transport perturbation. This principle reveals that auxin patterning is potentially controlled by multiple combinations of interlinked levels and localisation of influx and efflux carriers. We demonstrate that (1) when efflux carriers maintain polarity but change levels, maintaining the same auxin pattern requires non-uniform and polar distribution of influx carriers; (2) the emergence of the same auxin pattern, from different levels of influx carriers with the same nonpolar localisation, requires simultaneous modulation of efflux carrier level and polarity; and (3) multiple patterns of influx and efflux carriers for maintaining an auxin pattern do not have spatially proportional correlation. This reveals that auxin pattern formation requires coordination between influx and efflux carriers. We further show that the model makes various predictions that can be experimentally validated. PMID:28220889

  14. Metabolomic Analysis Provides Insights on Paraquat-Induced Parkinson-Like Symptoms in Drosophila melanogaster.

    Science.gov (United States)

    Shukla, Arvind Kumar; Ratnasekhar, Ch; Pragya, Prakash; Chaouhan, Hitesh Singh; Patel, Devendra Kumar; Chowdhuri, Debapratim Kar; Mudiam, Mohana Krishna Reddy

    2016-01-01

    Paraquat (PQ) exposure causes degeneration of the dopaminergic neurons in an exposed organism while altered metabolism has a role in various neurodegenerative disorders. Therefore, the study presented here was conceived to depict the role of altered metabolism in PQ-induced Parkinson-like symptoms and to explore Drosophila as a potential model organism for such studies. Metabolic profile was generated in control and in flies that were fed PQ (5, 10, and 20 mM) in the diet for 12 and 24 h concurrent with assessment of indices of oxidative stress, dopaminergic neurodegeneration, and behavioral alteration. PQ was found to significantly alter 24 metabolites belonging to different biological pathways along with significant alterations in the above indices. In addition, PQ attenuated brain dopamine content in the exposed organism. The study demonstrates that PQ-induced alteration in the metabolites leads to oxidative stress and neurodegeneration in the exposed organism along with movement disorder, a phenotype typical of Parkinson-like symptoms. The study is relevant in the context of Drosophila and humans because similar alteration in the metabolic pathways has been observed in both PQ-exposed Drosophila and in postmortem samples of patients with Parkinsonism. Furthermore, this study provides advocacy towards the applicability of Drosophila as an alternate model organism for pre-screening of environmental chemicals for their neurodegenerative potential with altered metabolism.

  15. Inferences from the historical distribution of wild and domesticated maize provide ecological and evolutionary insight.

    Directory of Open Access Journals (Sweden)

    Matthew B Hufford

    Full Text Available The species Zea mays includes both domesticated maize (ssp. mays and its closest wild relatives known as the teosintes. While genetic and archaeological studies have provided a well-established history of Z. mays evolution, there is currently minimal description of its current and past distribution. Here, we implemented species distribution modeling using paleoclimatic models of the last interglacial (LI; ∼135,000 BP and the last glacial maximum (LGM; ∼21,000 BP to hindcast the distribution of Zea mays subspecies over time and to revisit current knowledge of its phylogeography and evolutionary history.Using a large occurrence data set and the distribution modeling MaxEnt algorithm, we obtained robust present and past species distributions of the two widely distributed teosinte subspecies (ssps. parviglumis and mexicana revealing almost perfect complementarity, stable through time, of their occupied distributions. We also investigated the present distributions of primitive maize landraces, which overlapped but were broader than those of the teosintes. Our data reinforced the idea that little historical gene flow has occurred between teosinte subspecies, but maize has served as a genetic bridge between them. We observed an expansion of teosinte habitat from the LI, consistent with population genetic data. Finally, we identified locations potentially serving as refugia for the teosintes throughout epochs of climate change and sites that should be targeted in future collections.The restricted and highly contrasting ecological niches of the wild teosintes differ substantially from domesticated maize. Variables determining the distributions of these taxa can inform future considerations of local adaptation and the impacts of climate change. Our assessment of the changing distributions of Zea mays taxa over time offers a unique glimpse into the history of maize, highlighting a strategy for the study of domestication that may prove useful for other

  16. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness

    DEFF Research Database (Denmark)

    Willems, Sara M; Wright, Daniel J.; Day, Felix R

    2017-01-01

    with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip...... strength and the causal role of muscular strength in age-related morbidities and mortality....

  17. Flow-mediated dilation: can new approaches provide greater mechanistic insight into vascular dysfunction in preeclampsia and other diseases?

    Science.gov (United States)

    Weissgerber, Tracey L

    2014-11-01

    Endothelial dysfunction is a key feature of preeclampsia and may contribute to increased cardiovascular disease risk years after pregnancy. Flow-mediated dilation (FMD) is a non-invasive endothelial function test that predicts cardiovascular event risk. New protocols allow researchers to measure three components of the FMD response: FMD, low flow-mediated constriction, and shear stimulus. This review encourages researchers to think beyond "low FMD" by examining how these three components may provide additional insights into the mechanisms and location of vascular dysfunction. The review then examines what FMD studies reveal about vascular dysfunction in preeclampsia while highlighting opportunities to gain greater mechanistic insight from new protocols. Studies using traditional protocols show that FMD is low in mid-pregnancy prior to preeclampsia, at diagnosis, and for 3 years post-partum. However, FMD returns to normal by 10 years post-partum. Studies using new protocols are needed to gain more mechanistic insight.

  18. Pathway analysis of GWAS provides new insights into genetic susceptibility to 3 inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Hariklia Eleftherohorinou

    2009-11-01

    Full Text Available Although the introduction of genome-wide association studies (GWAS have greatly increased the number of genes associated with common diseases, only a small proportion of the predicted genetic contribution has so far been elucidated. Studying the cumulative variation of polymorphisms in multiple genes acting in functional pathways may provide a complementary approach to the more common single SNP association approach in understanding genetic determinants of common disease. We developed a novel pathway-based method to assess the combined contribution of multiple genetic variants acting within canonical biological pathways and applied it to data from 14,000 UK individuals with 7 common diseases. We tested inflammatory pathways for association with Crohn's disease (CD, rheumatoid arthritis (RA and type 1 diabetes (T1D with 4 non-inflammatory diseases as controls. Using a variable selection algorithm, we identified variants responsible for the pathway association and evaluated their use for disease prediction using a 10 fold cross-validation framework in order to calculate out-of-sample area under the Receiver Operating Curve (AUC. The generalisability of these predictive models was tested on an independent birth cohort from Northern Finland. Multiple canonical inflammatory pathways showed highly significant associations (p 10(-3-10(-20 with CD, T1D and RA. Variable selection identified on average a set of 205 SNPs (149 genes for T1D, 350 SNPs (189 genes for RA and 493 SNPs (277 genes for CD. The pattern of polymorphisms at these SNPS were found to be highly predictive of T1D (91% AUC and RA (85% AUC, and weakly predictive of CD (60% AUC. The predictive ability of the T1D model (without any parameter refitting had good predictive ability (79% AUC in the Finnish cohort. Our analysis suggests that genetic contribution to common inflammatory diseases operates through multiple genes interacting in functional pathways.

  19. Improved Ribosome-Footprint and mRNA Measurements Provide Insights into Dynamics and Regulation of Yeast Translation

    Science.gov (United States)

    2016-02-11

    unlimited. Improved Ribosome-Footprint and mRNA Measurements Provide Insights into Dynamics and Regulation of Yeast Translation The views, opinions and...into Dynamics and Regulation of Yeast Translation Report Title Ribosome-footprint profiling provides genome-wide snapshots of translation, but...tend to slow translation. With the improved mRNA measurements, the variation attributable to translational control in exponentially growing yeast was

  20. Analyses of pig genomes provide insight into porcine demography and evolution

    Science.gov (United States)

    Groenen, Martien A. M.; Archibald, Alan L.; Uenishi, Hirohide; Tuggle, Christopher K.; Takeuchi, Yasuhiro; Rothschild, Max F.; Rogel-Gaillard, Claire; Park, Chankyu; Milan, Denis; Megens, Hendrik-Jan; Li, Shengting; Larkin, Denis M.; Kim, Heebal; Frantz, Laurent A. F.; Caccamo, Mario; Ahn, Hyeonju; Aken, Bronwen L.; Anselmo, Anna; Anthon, Christian; Auvil, Loretta; Badaoui, Bouabid; Beattie, Craig W.; Bendixen, Christian; Berman, Daniel; Blecha, Frank; Blomberg, Jonas; Bolund, Lars; Bosse, Mirte; Botti, Sara; Bujie, Zhan; Bystrom, Megan; Capitanu, Boris; Silva, Denise Carvalho; Chardon, Patrick; Chen, Celine; Cheng, Ryan; Choi, Sang-Haeng; Chow, William; Clark, Richard C.; Clee, Christopher; Crooijmans, Richard P. M. A.; Dawson, Harry D.; Dehais, Patrice; De Sapio, Fioravante; Dibbits, Bert; Drou, Nizar; Du, Zhi-Qiang; Eversole, Kellye; Fadista, João; Fairley, Susan; Faraut, Thomas; Faulkner, Geoffrey J.; Fowler, Katie E.; Fredholm, Merete; Fritz, Eric; Gilbert, James G. R.; Giuffra, Elisabetta; Gorodkin, Jan; Griffin, Darren K.; Harrow, Jennifer L.; Hayward, Alexander; Howe, Kerstin; Hu, Zhi-Liang; Humphray, Sean J.; Hunt, Toby; Hornshøj, Henrik; Jeon, Jin-Tae; Jern, Patric; Jones, Matthew; Jurka, Jerzy; Kanamori, Hiroyuki; Kapetanovic, Ronan; Kim, Jaebum; Kim, Jae-Hwan; Kim, Kyu-Won; Kim, Tae-Hun; Larson, Greger; Lee, Kyooyeol; Lee, Kyung-Tai; Leggett, Richard; Lewin, Harris A.; Li, Yingrui; Liu, Wansheng; Loveland, Jane E.; Lu, Yao; Lunney, Joan K.; Ma, Jian; Madsen, Ole; Mann, Katherine; Matthews, Lucy; McLaren, Stuart; Morozumi, Takeya; Murtaugh, Michael P.; Narayan, Jitendra; Nguyen, Dinh Truong; Ni, Peixiang; Oh, Song-Jung; Onteru, Suneel; Panitz, Frank; Park, Eung-Woo; Park, Hong-Seog; Pascal, Geraldine; Paudel, Yogesh; Perez-Enciso, Miguel; Ramirez-Gonzalez, Ricardo; Reecy, James M.; Zas, Sandra Rodriguez; Rohrer, Gary A.; Rund, Lauretta; Sang, Yongming; Schachtschneider, Kyle; Schraiber, Joshua G.; Schwartz, John; Scobie, Linda; Scott, Carol; Searle, Stephen; Servin, Bertrand; Southey, Bruce R.; Sperber, Goran; Stadler, Peter; Sweedler, Jonathan V.; Tafer, Hakim; Thomsen, Bo; Wali, Rashmi; Wang, Jian; Wang, Jun; White, Simon; Xu, Xun; Yerle, Martine; Zhang, Guojie; Zhang, Jianguo; Zhang, Jie; Zhao, Shuhong; Rogers, Jane; Churcher, Carol; Schook, Lawrence B.

    2013-01-01

    For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ~1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model. PMID:23151582

  1. The Medicago Genome Provides Insight into the Evolution of Rhizobial Symbioses

    Science.gov (United States)

    Young, Nevin D.; Debellé, Frédéric; Oldroyd, Giles E. D.; Geurts, Rene; Cannon, Steven B.; Udvardi, Michael K.; Benedito, Vagner A.; Mayer, Klaus F. X.; Gouzy, Jérôme; Schoof, Heiko; Van de Peer, Yves; Proost, Sebastian; Cook, Douglas R.; Meyers, Blake C.; Spannagl, Manuel; Cheung, Foo; De Mita, Stéphane; Krishnakumar, Vivek; Gundlach, Heidrun; Zhou, Shiguo; Mudge, Joann; Bharti, Arvind K.; Murray, Jeremy D.; Naoumkina, Marina A.; Rosen, Benjamin; Silverstein, Kevin A. T.; Tang, Haibao; Rombauts, Stephane; Zhao, Patrick X.; Zhou, Peng; Barbe, Valérie; Bardou, Philippe; Bechner, Michael; Bellec, Arnaud; Berger, Anne; Bergès, Hélène; Bidwell, Shelby; Bisseling, Ton; Choisne, Nathalie; Couloux, Arnaud; Denny, Roxanne; Deshpande, Shweta; Dai, Xinbin; Doyle, Jeff; Dudez, Anne-Marie; Farmer, Andrew D.; Fouteau, Stéphanie; Franken, Carolien; Gibelin, Chrystel; Gish, John; Goldstein, Steven; González, Alvaro J.; Green, Pamela J.; Hallab, Asis; Hartog, Marijke; Hua, Axin; Humphray, Sean; Jeong, Dong-Hoon; Jing, Yi; Jöcker, Anika; Kenton, Steve M.; Kim, Dong-Jin; Klee, Kathrin; Lai, Hongshing; Lang, Chunting; Lin, Shaoping; Macmil, Simone L; Magdelenat, Ghislaine; Matthews, Lucy; McCorrison, Jamison; Monaghan, Erin L.; Mun, Jeong-Hwan; Najar, Fares Z.; Nicholson, Christine; Noirot, Céline; O’Bleness, Majesta; Paule, Charles R.; Poulain, Julie; Prion, Florent; Qin, Baifang; Qu, Chunmei; Retzel, Ernest F.; Riddle, Claire; Sallet, Erika; Samain, Sylvie; Samson, Nicolas; Sanders, Iryna; Saurat, Olivier; Scarpelli, Claude; Schiex, Thomas; Segurens, Béatrice; Severin, Andrew J.; Sherrier, D. Janine; Shi, Ruihua; Sims, Sarah; Singer, Susan R.; Sinharoy, Senjuti; Sterck, Lieven; Viollet, Agnès; Wang, Bing-Bing; Wang, Keqin; Wang, Mingyi; Wang, Xiaohong; Warfsmann, Jens; Weissenbach, Jean; White, Doug D.; White, Jim D.; Wiley, Graham B.; Wincker, Patrick; Xing, Yanbo; Yang, Limei; Yao, Ziyun; Ying, Fu; Zhai, Jixian; Zhou, Liping; Zuber, Antoine; Dénarié, Jean; Dixon, Richard A.; May, Gregory D.; Schwartz, David C.; Rogers, Jane; Quétier, Francis; Town, Christopher D.; Roe, Bruce A.

    2011-01-01

    Legumes (Fabaceae or Leguminosae) are unique among cultivated plants for their ability to carry out endosymbiotic nitrogen fixation with rhizobial bacteria, a process that takes place in a specialized structure known as the nodule. Legumes belong to one of the two main groups of eurosids, the Fabidae, which includes most species capable of endosymbiotic nitrogen fixation 1. Legumes comprise several evolutionary lineages derived from a common ancestor 60 million years ago (Mya). Papilionoids are the largest clade, dating nearly to the origin of legumes and containing most cultivated species 2. Medicago truncatula (Mt) is a long-established model for the study of legume biology. Here we describe the draft sequence of the Mt euchromatin based on a recently completed BAC-assembly supplemented with Illumina-shotgun sequence, together capturing ~94% of all Mt genes. A whole-genome duplication (WGD) approximately 58 Mya played a major role in shaping the Mt genome and thereby contributed to the evolution of endosymbiotic nitrogen fixation. Subsequent to the WGD, the Mt genome experienced higher levels of rearrangement than two other sequenced legumes, Glycine max (Gm) and Lotus japonicus (Lj). Mt is a close relative of alfalfa (M. sativa), a widely cultivated crop with limited genomics tools and complex autotetraploid genetics. As such, the Mt genome sequence provides significant opportunities to expand alfalfa’s genomic toolbox. PMID:22089132

  2. Plasmodium cynomolgi genome sequences provide insight into Plasmodium vivax and the monkey malaria clade.

    Science.gov (United States)

    Tachibana, Shin-Ichiro; Sullivan, Steven A; Kawai, Satoru; Nakamura, Shota; Kim, Hyunjae R; Goto, Naohisa; Arisue, Nobuko; Palacpac, Nirianne M Q; Honma, Hajime; Yagi, Masanori; Tougan, Takahiro; Katakai, Yuko; Kaneko, Osamu; Mita, Toshihiro; Kita, Kiyoshi; Yasutomi, Yasuhiro; Sutton, Patrick L; Shakhbatyan, Rimma; Horii, Toshihiro; Yasunaga, Teruo; Barnwell, John W; Escalante, Ananias A; Carlton, Jane M; Tanabe, Kazuyuki

    2012-09-01

    P. cynomolgi, a malaria-causing parasite of Asian Old World monkeys, is the sister taxon of P. vivax, the most prevalent malaria-causing species in humans outside of Africa. Because P. cynomolgi shares many phenotypic, biological and genetic characteristics with P. vivax, we generated draft genome sequences for three P. cynomolgi strains and performed genomic analysis comparing them with the P. vivax genome, as well as with the genome of a third previously sequenced simian parasite, Plasmodium knowlesi. Here, we show that genomes of the monkey malaria clade can be characterized by copy-number variants (CNVs) in multigene families involved in evasion of the human immune system and invasion of host erythrocytes. We identify genome-wide SNPs, microsatellites and CNVs in the P. cynomolgi genome, providing a map of genetic variation that can be used to map parasite traits and study parasite populations. The sequencing of the P. cynomolgi genome is a critical step in developing a model system for P. vivax research and in counteracting the neglect of P. vivax.

  3. RNA-Sequencing of Primary Retinoblastoma Tumors Provides New Insights and Challenges Into Tumor Development

    Directory of Open Access Journals (Sweden)

    Sailaja V. Elchuri

    2018-05-01

    Full Text Available Retinoblastoma is rare tumor of the retina caused by the homozygous loss of the Retinoblastoma 1 tumor suppressor gene (RB1. Loss of the RB1 protein, pRB, results in de-regulated activity of the E2F transcription factors, chromatin changes and developmental defects leading to tumor development. Extensive microarray profiles of these tumors have enabled the identification of genes sensitive to pRB disruption, however, this technology has a number of limitations in the RNA profiles that they generate. The advent of RNA-sequencing has enabled the global profiling of all of the RNA within the cell including both coding and non-coding features and the detection of aberrant RNA processing events. In this perspective, we focus on discussing how RNA-sequencing of rare Retinoblastoma tumors will build on existing data and open up new area’s to improve our understanding of the biology of these tumors. In particular, we discuss how the RB-research field may be to use this data to determine how RB1 loss results in the expression of; non-coding RNAs, causes aberrant RNA processing events and how a deeper analysis of metabolic RNA changes can be utilized to model tumor specific shifts in metabolism. Each section discusses new opportunities and challenges associated with these types of analyses and aims to provide an honest assessment of how understanding these different processes may contribute to the treatment of Retinoblastoma.

  4. Spider genomes provide insight into composition and evolution of venom and silk

    Science.gov (United States)

    Sanggaard, Kristian W.; Bechsgaard, Jesper S.; Fang, Xiaodong; Duan, Jinjie; Dyrlund, Thomas F.; Gupta, Vikas; Jiang, Xuanting; Cheng, Ling; Fan, Dingding; Feng, Yue; Han, Lijuan; Huang, Zhiyong; Wu, Zongze; Liao, Li; Settepani, Virginia; Thøgersen, Ida B.; Vanthournout, Bram; Wang, Tobias; Zhu, Yabing; Funch, Peter; Enghild, Jan J.; Schauser, Leif; Andersen, Stig U.; Villesen, Palle; Schierup, Mikkel H; Bilde, Trine; Wang, Jun

    2014-01-01

    Spiders are ecologically important predators with complex venom and extraordinarily tough silk that enables capture of large prey. Here we present the assembled genome of the social velvet spider and a draft assembly of the tarantula genome that represent two major taxonomic groups of spiders. The spider genomes are large with short exons and long introns, reminiscent of mammalian genomes. Phylogenetic analyses place spiders and ticks as sister groups supporting polyphyly of the Acari. Complex sets of venom and silk genes/proteins are identified. We find that venom genes evolved by sequential duplication, and that the toxic effect of venom is most likely activated by proteases present in the venom. The set of silk genes reveals a highly dynamic gene evolution, new types of silk genes and proteins, and a novel use of aciniform silk. These insights create new opportunities for pharmacological applications of venom and biomaterial applications of silk. PMID:24801114

  5. A holistic evolutionary and structural study of flaviviridae provides insights into the function and inhibition of HCV helicase

    Directory of Open Access Journals (Sweden)

    Dimitrios Vlachakis

    2013-05-01

    Full Text Available Viral RNA helicases are involved in duplex unwinding during the RNA replication of the virus. It is suggested that these helicases represent very promising antiviral targets. Viruses of the flaviviridae family are the causative agents of many common and devastating diseases, including hepatitis, yellow fever and dengue fever. As there is currently no available anti-Flaviviridae therapy, there is urgent need for the development of efficient anti-viral pharmaceutical strategies. Herein, we report the complete phylogenetic analysis across flaviviridae alongside a more in-depth evolutionary study that revealed a series of conserved and invariant amino acids that are predicted to be key to the function of the helicase. Structural molecular modelling analysis revealed the strategic significance of these residues based on their relative positioning on the 3D structures of the helicase enzymes, which may be used as pharmacological targets. We previously reported a novel series of highly potent HCV helicase inhibitors, and we now re-assess their antiviral potential using the 3D structural model of the invariant helicase residues. It was found that the most active compound of the series, compound C4, exhibited an IC50 in the submicromolar range, whereas its stereoisomer (compound C12 was completely inactive. Useful insights were obtained from molecular modelling and conformational search studies via molecular dynamics simulations. C12 tends to bend and lock in an almost “U” shape conformation, failing to establish vital interactions with the active site of HCV. On the contrary, C4 spends most of its conformational time in a straight, more rigid formation that allows it to successfully block the passage of the oligonucleotide in the ssRNA channel of the HCV helicase. This study paves the way and provides the necessary framework for the in-depth analysis required to enable the future design of new and potent anti-viral agents.

  6. Comparative transcriptional profiling provides insights into the evolution and development of the zygomorphic flower of Vicia sativa (Papilionoideae.

    Directory of Open Access Journals (Sweden)

    Zhipeng Liu

    Full Text Available BACKGROUND: Vicia sativa (the common vetch possesses a predominant zygomorphic flower and belongs to the subfamily Papilionoideae, which is related to Arabidopsis thaliana in the eurosid II clade of the core eudicots. Each vetch flower consists of 21 concentrically arranged organs: the outermost five sepals, then five petals and ten stamens, and a single carpel in the center. METHODOLOGY/PRINCIPAL FINDINGS: We explored the floral transcriptome to examine a genome-scale genetic model of the zygomorphic flower of vetch. mRNA was obtained from an equal mixture of six floral organs, leaves and roots. De novo assembly of the vetch transcriptome using Illumina paired-end technology produced 71,553 unigenes with an average length of 511 bp. We then compared the expression changes in the 71,553 unigenes in the eight independent organs through RNA-Seq Quantification analysis. We predominantly analyzed gene expression patterns specific to each floral organ and combinations of floral organs that corresponded to the traditional ABC model domains. Comparative analyses were performed in the floral transcriptomes of vetch and Arabidopsis, and genomes of vetch and Medicago truncatula. CONCLUSIONS/SIGNIFICANCE: Our comparative analysis of vetch and Arabidopsis showed that the vetch flowers conform to a strict ABC model. We analyzed the evolution and expression of the TCP gene family in vetch at a whole-genome level, and several unigenes specific to three different vetch petals, which might offer some clues toward elucidating the molecular mechanisms underlying floral zygomorphy. Our results provide the first insights into the genome-scale molecular regulatory network that controls the evolution and development of the zygomorphic flower in Papilionoideae.

  7. De novo Sequencing and Analysis of Lemongrass Transcriptome Provides First Insights into the Essential Oil Biosynthesis of Aromatic Grasses

    Directory of Open Access Journals (Sweden)

    Seema Meena

    2016-07-01

    Full Text Available Aromatic grasses of the genus Cymbopogon (Poaceae family represent unique group of plants that produce diverse composition of monoterpene rich essential oils, which have great value in flavour, fragrance, cosmetic and aromatherapy industries. Despite the commercial importance of these natural aromatic oils, their biosynthesis at the molecular level remains unexplored. As the first step towards understanding the essential oil biosynthesis, we performed de novo transcriptome assembly and analysis of C. flexuosus (lemongrass by employing Illumina sequencing. Mining of transcriptome data and subsequent phylogenetic analysis led to identification of terpene synthases (TPS, pyrophosphatases (PPase, alcohol dehydrogenases (ADH, aldo-keto reductases (AKR, carotenoid cleavage dioxygenases (CCD, alcohol acetyltransferases (AAT and aldehyde dehydrogenases (ALDH, which are potentially involved in essential oil biosynthesis. Comparative essential oil profiling and mRNA expression analysis in three Cymbopogon species (C. flexuosus, aldehyde type; C. martinii, alcohol type; and C. winterianus, intermediate type with varying essential oil composition indicated the involvement of identified candidate genes in the formation of alcohols, aldehydes and acetates. Molecular modeling and docking further supported the role of identified enzymes in aroma formation in Cymbopogon. Also, simple sequence repeats (SSRs were found in the transcriptome with many linked to terpene pathway genes including the genes potentially involved in aroma biosynthesis. This work provides the first insights into the essential oil biosynthesis of aromatic grasses, and the identified candidate genes and markers can be a great resource for biotechnological and molecular breeding approaches to modulate the essential oil composition.

  8. De Novo Sequencing and Analysis of Lemongrass Transcriptome Provide First Insights into the Essential Oil Biosynthesis of Aromatic Grasses.

    Science.gov (United States)

    Meena, Seema; Kumar, Sarma R; Venkata Rao, D K; Dwivedi, Varun; Shilpashree, H B; Rastogi, Shubhra; Shasany, Ajit K; Nagegowda, Dinesh A

    2016-01-01

    Aromatic grasses of the genus Cymbopogon (Poaceae family) represent unique group of plants that produce diverse composition of monoterpene rich essential oils, which have great value in flavor, fragrance, cosmetic, and aromatherapy industries. Despite the commercial importance of these natural aromatic oils, their biosynthesis at the molecular level remains unexplored. As the first step toward understanding the essential oil biosynthesis, we performed de novo transcriptome assembly and analysis of C. flexuosus (lemongrass) by employing Illumina sequencing. Mining of transcriptome data and subsequent phylogenetic analysis led to identification of terpene synthases, pyrophosphatases, alcohol dehydrogenases, aldo-keto reductases, carotenoid cleavage dioxygenases, alcohol acetyltransferases, and aldehyde dehydrogenases, which are potentially involved in essential oil biosynthesis. Comparative essential oil profiling and mRNA expression analysis in three Cymbopogon species (C. flexuosus, aldehyde type; C. martinii, alcohol type; and C. winterianus, intermediate type) with varying essential oil composition indicated the involvement of identified candidate genes in the formation of alcohols, aldehydes, and acetates. Molecular modeling and docking further supported the role of identified protein sequences in aroma formation in Cymbopogon. Also, simple sequence repeats were found in the transcriptome with many linked to terpene pathway genes including the genes potentially involved in aroma biosynthesis. This work provides the first insights into the essential oil biosynthesis of aromatic grasses, and the identified candidate genes and markers can be a great resource for biotechnological and molecular breeding approaches to modulate the essential oil composition.

  9. De Novo Sequencing and Analysis of Lemongrass Transcriptome Provide First Insights into the Essential Oil Biosynthesis of Aromatic Grasses

    Science.gov (United States)

    Meena, Seema; Kumar, Sarma R.; Venkata Rao, D. K.; Dwivedi, Varun; Shilpashree, H. B.; Rastogi, Shubhra; Shasany, Ajit K.; Nagegowda, Dinesh A.

    2016-01-01

    Aromatic grasses of the genus Cymbopogon (Poaceae family) represent unique group of plants that produce diverse composition of monoterpene rich essential oils, which have great value in flavor, fragrance, cosmetic, and aromatherapy industries. Despite the commercial importance of these natural aromatic oils, their biosynthesis at the molecular level remains unexplored. As the first step toward understanding the essential oil biosynthesis, we performed de novo transcriptome assembly and analysis of C. flexuosus (lemongrass) by employing Illumina sequencing. Mining of transcriptome data and subsequent phylogenetic analysis led to identification of terpene synthases, pyrophosphatases, alcohol dehydrogenases, aldo-keto reductases, carotenoid cleavage dioxygenases, alcohol acetyltransferases, and aldehyde dehydrogenases, which are potentially involved in essential oil biosynthesis. Comparative essential oil profiling and mRNA expression analysis in three Cymbopogon species (C. flexuosus, aldehyde type; C. martinii, alcohol type; and C. winterianus, intermediate type) with varying essential oil composition indicated the involvement of identified candidate genes in the formation of alcohols, aldehydes, and acetates. Molecular modeling and docking further supported the role of identified protein sequences in aroma formation in Cymbopogon. Also, simple sequence repeats were found in the transcriptome with many linked to terpene pathway genes including the genes potentially involved in aroma biosynthesis. This work provides the first insights into the essential oil biosynthesis of aromatic grasses, and the identified candidate genes and markers can be a great resource for biotechnological and molecular breeding approaches to modulate the essential oil composition. PMID:27516768

  10. Clustering of Pan- and Core-genome of Lactobacillus provides Novel Evolutionary Insights for Differentiation.

    Science.gov (United States)

    Inglin, Raffael C; Meile, Leo; Stevens, Marc J A

    2018-04-24

    Bacterial taxonomy aims to classify bacteria based on true evolutionary events and relies on a polyphasic approach that includes phenotypic, genotypic and chemotaxonomic analyses. Until now, complete genomes are largely ignored in taxonomy. The genus Lactobacillus consists of 173 species and many genomes are available to study taxonomy and evolutionary events. We analyzed and clustered 98 completely sequenced genomes of the genus Lactobacillus and 234 draft genomes of 5 different Lactobacillus species, i.e. L. reuteri, L. delbrueckii, L. plantarum, L. rhamnosus and L. helveticus. The core-genome of the genus Lactobacillus contains 266 genes and the pan-genome 20'800 genes. Clustering of the Lactobacillus pan- and core-genome resulted in two highly similar trees. This shows that evolutionary history is traceable in the core-genome and that clustering of the core-genome is sufficient to explore relationships. Clustering of core- and pan-genomes at species' level resulted in similar trees as well. Detailed analyses of the core-genomes showed that the functional class "genetic information processing" is conserved in the core-genome but that "signaling and cellular processes" is not. The latter class encodes functions that are involved in environmental interactions. Evolution of lactobacilli seems therefore directed by the environment. The type species L. delbrueckii was analyzed in detail and its pan-genome based tree contained two major clades whose members contained different genes yet identical functions. In addition, evidence for horizontal gene transfer between strains of L. delbrueckii, L. plantarum, and L. rhamnosus, and between species of the genus Lactobacillus is presented. Our data provide evidence for evolution of some lactobacilli according to a parapatric-like model for species differentiation. Core-genome trees are useful to detect evolutionary relationships in lactobacilli and might be useful in taxonomic analyses. Lactobacillus' evolution is directed

  11. Genetic Aspects of Autism Spectrum Disorders: Insights from Animal Models

    Directory of Open Access Journals (Sweden)

    Swati eBanerjee

    2014-02-01

    Full Text Available Autism spectrum disorders (ASD are a complex neurodevelopmental disorder that display a triad of core behavioral deficits including restricted interests, often accompanied by repetitive behavior, deficits in language and communication, and an inability to engage in reciprocal social interactions. ASD is among the most heritable disorders but is not a simple disorder with a singular pathology and has a rather complex etiology. It is interesting to note that perturbations in synaptic growth, development and stability underlie a variety of neuropsychiatric disorders, including ASD, schizophrenia, epilepsy and intellectual disability. Biological characterization of an increasing repertoire of synaptic mutants in various model organisms indicates synaptic dysfunction as causal in the pathophysiology of ASD. Our understanding of the genes and genetic pathways that contribute towards the formation, stabilization and maintenance of functional synapses coupled with an in-depth phenotypic analysis of the cellular and behavioral characteristics is therefore essential to unraveling the pathogenesis of these disorders. In this review, we discuss the genetic aspects of ASD emphasizing on the well conserved set of genes and genetic pathways implicated in this disorder, many of which contribute to synapse assembly and maintenance across species. We also review how fundamental research using animal models is providing key insights into the various facets of human ASD.

  12. Solitary mammals provide an animal model for autism spectrum disorders.

    Science.gov (United States)

    Reser, Jared Edward

    2014-02-01

    Species of solitary mammals are known to exhibit specialized, neurological adaptations that prepare them to focus working memory on food procurement and survival rather than on social interaction. Solitary and nonmonogamous mammals, which do not form strong social bonds, have been documented to exhibit behaviors and biomarkers that are similar to endophenotypes in autism. Both individuals on the autism spectrum and certain solitary mammals have been reported to be low on measures of affiliative need, bodily expressiveness, bonding and attachment, direct and shared gazing, emotional engagement, conspecific recognition, partner preference, separation distress, and social approach behavior. Solitary mammals also exhibit certain biomarkers that are characteristic of autism, including diminished oxytocin and vasopressin signaling, dysregulation of the endogenous opioid system, increased Hypothalamic-pituitary-adrenal axis (HPA) activity to social encounters, and reduced HPA activity to separation and isolation. The extent of these similarities suggests that solitary mammals may offer a useful model of autism spectrum disorders and an opportunity for investigating genetic and epigenetic etiological factors. If the brain in autism can be shown to exhibit distinct homologous or homoplastic similarities to the brains of solitary animals, it will reveal that they may be central to the phenotype and should be targeted for further investigation. Research of the neurological, cellular, and molecular basis of these specializations in other mammals may provide insight for behavioral analysis, communication intervention, and psychopharmacology for autism.

  13. Structural studies of Pseudomonas and Chromobacterium ω-aminotransferases provide insights into their differing substrate specificity

    International Nuclear Information System (INIS)

    Sayer, Christopher; Isupov, Michail N.; Westlake, Aaron; Littlechild, Jennifer A.

    2013-01-01

    The X-ray structures of two ω-aminotransferases from P. aeruginosa and C. violaceum in complex with an inhibitor offer the first detailed insight into the structural basis of the substrate specificity of these industrially important enzymes. The crystal structures and inhibitor complexes of two industrially important ω-aminotransferase enzymes from Pseudomonas aeruginosa and Chromobacterium violaceum have been determined in order to understand the differences in their substrate specificity. The two enzymes share 30% sequence identity and use the same amino acceptor, pyruvate; however, the Pseudomonas enzyme shows activity towards the amino donor β-alanine, whilst the Chromobacterium enzyme does not. Both enzymes show activity towards S-α-methylbenzylamine (MBA), with the Chromobacterium enzyme having a broader substrate range. The crystal structure of the P. aeruginosa enzyme has been solved in the holo form and with the inhibitor gabaculine bound. The C. violaceum enzyme has been solved in the apo and holo forms and with gabaculine bound. The structures of the holo forms of both enzymes are quite similar. There is little conformational difference observed between the inhibitor complex and the holoenzyme for the P. aeruginosa aminotransferase. In comparison, the crystal structure of the C. violaceum gabaculine complex shows significant structural rearrangements from the structures of both the apo and holo forms of the enzyme. It appears that the different rigidity of the protein scaffold contributes to the substrate specificity observed for the two ω-aminotransferases

  14. The elite cross-country skier provides unique insights into human exercise physiology.

    Science.gov (United States)

    Holmberg, H-C

    2015-12-01

    Successful cross-country skiing, one of the most demanding of endurance sports, involves considerable physiological challenges posed by the combined upper- and lower-body effort of varying intensity and duration, on hilly terrain, often at moderate altitude and in a cold environment. Over the years, this unique sport has helped physiologists gain novel insights into the limits of human performance and regulatory capacity. There is a long-standing tradition of researchers in this field working together with coaches and athletes to improve training routines, monitor progress, and refine skiing techniques. This review summarizes research on elite cross-country skiers, with special emphasis on the studies initiated by Professor Bengt Saltin. He often employed exercise as a means to learn more about the human body, successfully engaging elite endurance athletes to improve our understanding of the demands, characteristics, and specific effects associated with different types of exercise. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. The correlation between gelatin macroscale differences and nanoparticle properties: providing insight into biopolymer variability.

    Science.gov (United States)

    Stevenson, André T; Jankus, Danny J; Tarshis, Max A; Whittington, Abby R

    2018-05-21

    From therapeutic delivery to sustainable packaging, manipulation of biopolymers into nanostructures imparts biocompatibility to numerous materials with minimal environmental pollution during processing. While biopolymers are appealing natural based materials, the lack of nanoparticle (NP) physicochemical consistency has decreased their nanoscale translation into actual products. Insights regarding the macroscale and nanoscale property variation of gelatin, one of the most common biopolymers already utilized in its bulk form, are presented. Novel correlations between macroscale and nanoscale properties were made by characterizing similar gelatin rigidities obtained from different manufacturers. Samples with significant differences in clarity, indicating sample purity, obtained the largest deviations in NP diameter. Furthermore, a statistically significant positive correlation between macroscale molecular weight dispersity and NP diameter was determined. New theoretical calculations proposing the limited number of gelatin chains that can aggregate and subsequently get crosslinked for NP formation were presented as one possible reason to substantiate the correlation analysis. NP charge and crosslinking extent were also related to diameter. Lower gelatin sample molecular weight dispersities produced statistically smaller average diameters (<75 nm), and higher average electrostatic charges (∼30 mV) and crosslinking extents (∼95%), which were independent of gelatin rigidity, conclusions not shown in the literature. This study demonstrates that the molecular weight composition of the starting material is one significant factor affecting gelatin nanoscale properties and must be characterized prior to NP preparation. Identifying gelatin macroscale and nanoscale correlations offers a route toward greater physicochemical property control and reproducibility of new NP formulations for translation to industry.

  16. Human listeners provide insights into echo features used by dolphins (Tursiops truncatus) to discriminate among objects.

    Science.gov (United States)

    Delong, Caroline M; Au, Whitlow W L; Harley, Heidi E; Roitblat, Herbert L; Pytka, Lisa

    2007-08-01

    Echolocating bottlenose dolphins (Tursiops truncatus) discriminate between objects on the basis of the echoes reflected by the objects. However, it is not clear which echo features are important for object discrimination. To gain insight into the salient features, the authors had a dolphin perform a match-to-sample task and then presented human listeners with echoes from the same objects used in the dolphin's task. In 2 experiments, human listeners performed as well or better than the dolphin at discriminating objects, and they reported the salient acoustic cues. The error patterns of the humans and the dolphin were compared to determine which acoustic features were likely to have been used by the dolphin. The results indicate that the dolphin did not appear to use overall echo amplitude, but that it attended to the pattern of changes in the echoes across different object orientations. Human listeners can quickly identify salient combinations of echo features that permit object discrimination, which can be used to generate hypotheses that can be tested using dolphins as subjects.

  17. Comprehensive transcriptome analysis provides new insights into nutritional strategies and phylogenetic relationships of chrysophytes

    Directory of Open Access Journals (Sweden)

    Daniela Beisser

    2017-01-01

    Full Text Available Background Chrysophytes are protist model species in ecology and ecophysiology and important grazers of bacteria-sized microorganisms and primary producers. However, they have not yet been investigated in detail at the molecular level, and no genomic and only little transcriptomic information is available. Chrysophytes exhibit different trophic modes: while phototrophic chrysophytes perform only photosynthesis, mixotrophs can gain carbon from bacterial food as well as from photosynthesis, and heterotrophs solely feed on bacteria-sized microorganisms. Recent phylogenies and megasystematics demonstrate an immense complexity of eukaryotic diversity with numerous transitions between phototrophic and heterotrophic organisms. The question we aim to answer is how the diverse nutritional strategies, accompanied or brought about by a reduction of the plasmid and size reduction in heterotrophic strains, affect physiology and molecular processes. Results We sequenced the mRNA of 18 chrysophyte strains on the Illumina HiSeq platform and analysed the transcriptomes to determine relations between the trophic mode (mixotrophic vs. heterotrophic and gene expression. We observed an enrichment of genes for photosynthesis, porphyrin and chlorophyll metabolism for phototrophic and mixotrophic strains that can perform photosynthesis. Genes involved in nutrient absorption, environmental information processing and various transporters (e.g., monosaccharide, peptide, lipid transporters were present or highly expressed only in heterotrophic strains that have to sense, digest and absorb bacterial food. We furthermore present a transcriptome-based alignment-free phylogeny construction approach using transcripts assembled from short reads to determine the evolutionary relationships between the strains and the possible influence of nutritional strategies on the reconstructed phylogeny. We discuss the resulting phylogenies in comparison to those from established approaches

  18. Economic Insights into Providing Access to Improved Groundwater Sources in Remote, Low-Resource Areas

    Science.gov (United States)

    Abramson, A.; Lazarovitch, N.; Adar, E.

    2013-12-01

    Groundwater is often the most or only feasible drinking water source in remote, low-resource areas. Yet the economics of its development have not been systematically outlined. We applied CBARWI (Cost-Benefit Analysis for Remote Water Improvements), a recently developed Decision Support System, to investigate the economic, physical and management factors related to the costs and benefits of non-networked groundwater supply in remote areas. Synthetic profiles of community water services (n = 17,962), defined across 14 parameters' values and ranges relevant to remote areas, were imputed into the decision framework, and the parameter effects on economic outcomes were investigated through regression analysis (Table 1). Several approaches were included for financing the improvements, after Abramson et al, 2011: willingness-to -pay (WTP), -borrow (WTB) and -work (WTW) in community irrigation (';water-for-work'). We found that low-cost groundwater development approaches are almost 7 times more cost-effective than conventional boreholes fitted with handpumps. The costs of electric, submersible borehole pumps are comparable only when providing expanded water supplies, and off-grid communities pay significantly more for such expansions. In our model, new source construction is less cost-effective than improvement of existing wells, but necessary for expanding access to isolated households. The financing approach significantly impacts the feasibility of demand-driven cost recovery; in our investigation, benefit exceeds cost in 16, 32 and 48% of water service configurations financed by WTP, WTB and WTW, respectively. Regressions of total cost (R2 = 0.723) and net benefit under WTW (R2 = 0.829) along with analysis of output distributions indicate that parameters determining the profitability of irrigation are different from those determining costs and other measures of net benefit. These findings suggest that the cost-benefit outcomes associated with groundwater-based water

  19. The Turbulent Interstellar Medium: Insights and Questions from Numerical Models

    OpenAIRE

    Mac Low, Mordecai-Mark; de Avillez, Miguel A.; Korpi, Maarit J.

    2003-01-01

    "The purpose of numerical models is not numbers but insight." (Hamming) In the spirit of this adage, and of Don Cox's approach to scientific speaking, we discuss the questions that the latest generation of numerical models of the interstellar medium raise, at least for us. The energy source for the interstellar turbulence is still under discussion. We review the argument for supernovae dominating in star forming regions. Magnetorotational instability has been suggested as a way of coupling di...

  20. Stents: Biomechanics, Biomaterials, and Insights from Computational Modeling.

    Science.gov (United States)

    Karanasiou, Georgia S; Papafaklis, Michail I; Conway, Claire; Michalis, Lampros K; Tzafriri, Rami; Edelman, Elazer R; Fotiadis, Dimitrios I

    2017-04-01

    Coronary stents have revolutionized the treatment of coronary artery disease. Improvement in clinical outcomes requires detailed evaluation of the performance of stent biomechanics and the effectiveness as well as safety of biomaterials aiming at optimization of endovascular devices. Stents need to harmonize the hemodynamic environment and promote beneficial vessel healing processes with decreased thrombogenicity. Stent design variables and expansion properties are critical for vessel scaffolding. Drug-elution from stents, can help inhibit in-stent restenosis, but adds further complexity as drug release kinetics and coating formulations can dominate tissue responses. Biodegradable and bioabsorbable stents go one step further providing complete absorption over time governed by corrosion and erosion mechanisms. The advances in computing power and computational methods have enabled the application of numerical simulations and the in silico evaluation of the performance of stent devices made up of complex alloys and bioerodible materials in a range of dimensions and designs and with the capacity to retain and elute bioactive agents. This review presents the current knowledge on stent biomechanics, stent fatigue as well as drug release and mechanisms governing biodegradability focusing on the insights from computational modeling approaches.

  1. New data from Virginia Tech Transportation Institute provides insight into cell phone use and driving distraction

    OpenAIRE

    Box, Sherri

    2009-01-01

    Several large-scale, naturalistic driving studies -- using sophisticated cameras and instrumentation in participants' personal vehicles -- conducted by the Virginia Tech Transportation Institute (VTTI), provide a clear picture of driver distraction and cell phone use under real-world driving conditions, according to the institute.

  2. The impact of the business cycle on service providers : Insights from international tourism

    NARCIS (Netherlands)

    Dekimpe, Marnik; Peers, Yuri; van Heerde, H.J.

    For service providers, it is essential to understand how their business is affected by the macroeconomy. This is especially pressing for the tourism sector, the world’s largest export service, because the number of incoming visitors is likely to be strongly determined by the business cycles in the

  3. Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes.

    Science.gov (United States)

    You, Xinxin; Bian, Chao; Zan, Qijie; Xu, Xun; Liu, Xin; Chen, Jieming; Wang, Jintu; Qiu, Ying; Li, Wujiao; Zhang, Xinhui; Sun, Ying; Chen, Shixi; Hong, Wanshu; Li, Yuxiang; Cheng, Shifeng; Fan, Guangyi; Shi, Chengcheng; Liang, Jie; Tom Tang, Y; Yang, Chengye; Ruan, Zhiqiang; Bai, Jie; Peng, Chao; Mu, Qian; Lu, Jun; Fan, Mingjun; Yang, Shuang; Huang, Zhiyong; Jiang, Xuanting; Fang, Xiaodong; Zhang, Guojie; Zhang, Yong; Polgar, Gianluca; Yu, Hui; Li, Jia; Liu, Zhongjian; Zhang, Guoqiang; Ravi, Vydianathan; Coon, Steven L; Wang, Jian; Yang, Huanming; Venkatesh, Byrappa; Wang, Jun; Shi, Qiong

    2014-12-02

    Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers' tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates.

  4. Precision Neutron Time-of-Flight Detectors Provide Insight into NIF Implosion Dynamics

    Science.gov (United States)

    Schlossberg, David; Eckart, M. J.; Grim, G. P.; Hartouni, E. P.; Hatarik, R.; Moore, A. S.; Waltz, C. S.

    2017-10-01

    During inertial confinement fusion, higher-order moments of neutron time-of-flight (nToF) spectra can provide essential information for optimizing implosions. The nToF diagnostic suite at the National Ignition Facility (NIF) was recently upgraded to include novel, quartz Cherenkov detectors. These detectors exploit the rapid Cherenkov radiation process, in contrast with conventional scintillator decay times, to provide high temporal-precision measurements that support higher-order moment analyses. Preliminary measurements have been made on the NIF during several implosions and initial results are presented here. Measured line-of-sight asymmetries, for example in ion temperatures, will be discussed. Finally, advanced detector optimization is shown to advance accessible physics, with possibilities for energy discrimination, gamma source identification, and further reduction in quartz response times. Work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344.

  5. Stable isotopes provide insight into population structure and segregation in eastern North Atlantic sperm whales

    DEFF Research Database (Denmark)

    Borrell, Asunción; Velásquez Vacca, Adriana; Pinela, Ana M.

    2013-01-01

    In pelagic species inhabiting large oceans, genetic differentiation tends to be mild and populations devoid of structure. However, large cetaceans have provided many examples of structuring. Here we investigate whether the sperm whale, a pelagic species with large population sizes and reputedly......, use of habitat and/or migratory destinations are dissimilar between whales from the two regions and suggest that the North Atlantic population of sperm whales is more structured than traditionally accepted....

  6. Stable isotopes provide new insights into vestimentiferan physiological ecology at Gulf of Mexico cold seeps

    Science.gov (United States)

    Becker, Erin Leigh; Macko, Stephen A.; Lee, Raymond W.; Fisher, Charles R.

    2011-02-01

    On the otherwise low-biomass seafloor of the Gulf of Mexico (GoM) continental slope, natural oil and gas seeps are oases of local primary production that support lush animal communities. Hundreds of seep communities have been documented on the continental slope, and nutrition derived from seeps could be an important link in the overall GoM food web. Here, we present a uniquely large and cohesive data set of δ13C, δ15N, and δ34S compositions of the vestimentiferan tubeworms Escarpia laminata and Lamellibrachia sp. 1, which dominate biomass at GoM seeps and provide habitat for hundreds of other species. Our sampling design encompassed an entire region of the GoM lower slope, allowing us for the first time to assess spatial variability in isotope compositions and to robustly address long-standing hypotheses about how vestimentiferans acquire and cycle nutrients over their long lifespan (200+ years). Tissue δ13C values provided strong evidence that larger adult vestimentiferans use their buried roots to take up dissolved inorganic carbon from sediment pore water, while very small individuals use their plume to take up carbon dioxide from the seawater. δ34S values were extremely variable among individuals of the same species within one location (<1 m2 area), indicating high variability in the inorganic sulfur pools on a very small spatial scale. This finding supports the hypothesis that vestimentiferans use their roots to cycle sulfate and sulfide between their symbionts and free-living consortia of sulfate-reducing archaea in the sediment. Finally, consistent differences in δ15N between two cooccurring vestimentiferan species provided the first strong evidence for partitioning of inorganic resources, which has significant implications for the ecology and evolution of this taxonomic group.

  7. Quantitative measures of walking and strength provide insight into brain corticospinal tract pathology in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Nora E Fritz

    2017-01-01

    Quantitative measures of strength and walking are associated with brain corticospinal tract pathology. The addition of these quantitative measures to basic clinical information explains more of the variance in corticospinal tract fractional anisotropy and magnetization transfer ratio than the basic clinical information alone. Outcome measurement for multiple sclerosis clinical trials has been notoriously challenging; the use of quantitative measures of strength and walking along with tract-specific imaging methods may improve our ability to monitor disease change over time, with intervention, and provide needed guidelines for developing more effective targeted rehabilitation strategies.

  8. Analyzing Arabidopsis thaliana root proteome provides insights into the molecular bases of enantioselective imazethapyr toxicity

    Science.gov (United States)

    Qian, Haifeng; Lu, Haiping; Ding, Haiyan; Lavoie, Michel; Li, Yali; Liu, Weiping; Fu, Zhengwei

    2015-07-01

    Imazethapyr (IM) is a widely used chiral herbicide that inhibits the synthesis of branched-chain amino acids (BCAAs). IM is thought to exert its toxic effects on amino acid synthesis mainly through inhibition of acetolactate synthase activity, but little is known about the potential effects of IM on other key biochemical pathways. Here, we exposed the model plant Arabidospsis thaliana to trace S- and R-IM enantiomer concentrations and examined IM toxicity effects on the root proteome using iTRAQ. Conventional analyses of root carbohydrates, organic acids, and enzyme activities were also performed. We discovered several previously unknown key biochemical pathways targeted by IM in Arabidospsis. 1,322 and 987 proteins were differentially expressed in response to R- and S-IM treatments, respectively. Bioinformatics and physiological analyses suggested that IM reduced the BCAA tissue content not only by strongly suppressing BCAA synthesis but also by increasing BCAA catabolism. IM also affected sugar and starch metabolism, changed the composition of root cell walls, increased citrate production and exudation, and affected the microbial community structure of the rhizosphere. The present study shed new light on the multiple toxicity mechanisms of a selective herbicide on a model plant.

  9. Can administrative data provide insights into the mental health of Indigenous Queenslanders?

    Science.gov (United States)

    Kisely, Steve; Pais, Joanne

    2011-07-01

    The Australian Government has provided $20 million to establish the Population Health Research Network (PHRN), with representation from all States and Territories to facilitate population health research through data linkage. Health LinQ is part of the Queensland node involving four Queensland universities, Queensland Health and the Australian e-Health Research Centre. This paper reviews the potential for using administrative databases to study the mental health experience of Indigenous Queenslanders. Researchers can define cohorts for study within the administrative data or link them to their own data. Robust protocols preserve confidentiality so that researchers only receive anonymized data. Indigenous status can be defined either through place of residence or through the recording of Indigenous status in datasets such as the Queensland Hospital Admitted Patient Data Collection. Available data include hospital morbidity, mental health data and mortality. Indigenous status is correctly identified in about 89% of cases with variation by definition used. Administrative data provide researchers and decision makers with accessible, cost-effective information without the intrusion and cost of additional data collection. These techniques are especially useful in studying regional, rural and remote populations where access may be difficult.

  10. Atomic Force Microscopy Provides New Mechanistic Insights into the Pathogenesis of Pemphigus

    Directory of Open Access Journals (Sweden)

    Franziska Vielmuth

    2018-03-01

    Full Text Available Autoantibodies binding to the extracellular domains of desmoglein (Dsg 3 and 1 are critical in the pathogenesis of pemphigus by mechanisms leading to impaired function of desmosomes and blister formation in the epidermis and mucous membranes. Desmosomes are highly organized protein complexes which provide strong intercellular adhesion. Desmosomal cadherins such as Dsgs, proteins of the cadherin superfamily which interact via their extracellular domains in Ca2+-dependent manner, are the transmembrane adhesion molecules clustered within desmosomes. Investigations on pemphigus cover a wide range of experimental approaches including biophysical methods. Especially atomic force microscopy (AFM has recently been applied increasingly because it allows the analysis of native materials such as cultured cells and tissues under near-physiological conditions. AFM provides information about the mechanical properties of the sample together with detailed interaction analyses of adhesion molecules. With AFM, it was recently demonstrated that autoantibodies directly inhibit Dsg interactions on the surface of living keratinocytes, a phenomenon which has long been considered the main mechanism causing loss of cell cohesion in pemphigus. In addition, AFM allows to study how signaling pathways altered in pemphigus control binding properties of Dsgs. More general, AFM and other biophysical studies recently revealed the importance of keratin filaments for regulation of Dsg binding and keratinocyte mechanical properties. In this mini-review, we reevaluate AFM studies in pemphigus and keratinocyte research, recapitulate what is known about the interaction mechanisms of desmosomal cadherins and discuss the advantages and limitations of AFM in these regards.

  11. Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization

    Science.gov (United States)

    Qin, Cheng; Yu, Changshui; Shen, Yaou; Fang, Xiaodong; Chen, Lang; Min, Jiumeng; Cheng, Jiaowen; Zhao, Shancen; Xu, Meng; Luo, Yong; Yang, Yulan; Wu, Zhiming; Mao, Likai; Wu, Haiyang; Ling-Hu, Changying; Zhou, Huangkai; Lin, Haijian; González-Morales, Sandra; Trejo-Saavedra, Diana L.; Tian, Hao; Tang, Xin; Zhao, Maojun; Huang, Zhiyong; Zhou, Anwei; Yao, Xiaoming; Cui, Junjie; Li, Wenqi; Chen, Zhe; Feng, Yongqiang; Niu, Yongchao; Bi, Shimin; Yang, Xiuwei; Li, Weipeng; Cai, Huimin; Luo, Xirong; Montes-Hernández, Salvador; Leyva-González, Marco A.; Xiong, Zhiqiang; He, Xiujing; Bai, Lijun; Tan, Shu; Tang, Xiangqun; Liu, Dan; Liu, Jinwen; Zhang, Shangxing; Chen, Maoshan; Zhang, Lu; Zhang, Li; Zhang, Yinchao; Liao, Weiqin; Zhang, Yan; Wang, Min; Lv, Xiaodan; Wen, Bo; Liu, Hongjun; Luan, Hemi; Zhang, Yonggang; Yang, Shuang; Wang, Xiaodian; Xu, Jiaohui; Li, Xueqin; Li, Shuaicheng; Wang, Junyi; Palloix, Alain; Bosland, Paul W.; Li, Yingrui; Krogh, Anders; Rivera-Bustamante, Rafael F.; Herrera-Estrella, Luis; Yin, Ye; Yu, Jiping; Hu, Kailin; Zhang, Zhiming

    2014-01-01

    As an economic crop, pepper satisfies people’s spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded ∼0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of ∼81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs. PMID:24591624

  12. NRC test results and operations experience provide insights for a new gate valve stem force correlation

    International Nuclear Information System (INIS)

    Watkins, John C.; Steele, Robert Jr.; DeWall, Kevin G.; Weidenhamer, G.H.; Rothberg, O.O.

    1994-01-01

    This paper presents the results of testing sponsored by the NRC to assess valve and motor operator performance under varying pressure and fluid conditions. This effort included an examination of the methods used by the industry to predict the required stem force of a valve, and research to provide guidelines for the extrapolation of in situ test results to design basis conditions.Years ago, when most of these valves were originally installed, the industry used a set of equations to determine analytically that the valves' motor-operators were large enough and the control switches were set high enough to close the valves at their design basis conditions. Our research has identified several inconsistencies with the industry's existing gate valve stem force equation and has challenged the overly simplistic assumptions inherent in its use. This paper discusses the development of the INEL correlation, which serves as the basis for a method to bound the stem force necessary to close flexwedge gate valves whose operational characteristics have been shown to be predictable. As utilities undertake to provide assurance of their valves' operability, this ability to predict analytically the required stem force is especially important for valves that cannot be tested at design basis conditions. For such valves, the results of tests conducted at less severe conditions can be used with the INEL correlation to make the necessary prediction. ((orig.))

  13. New technological developments provide deep-sea sediment density flow insights: the Monterey Coordinated Canyon Experiment

    Science.gov (United States)

    O'Reilly, T. C.; Kieft, B.; Chaffey, M. R.; Wolfson-Schwehr, M.; Herlien, R.; Bird, L.; Klimov, D.; Paull, C. K.; Gwiazda, R.; Lundsten, E. M.; Anderson, K.; Caress, D. W.; Sumner, E. J.; Simmons, S.; Parsons, D. R.; Talling, P.; Rosenberger, K. J.; Xu, J.; Maier, K. L.; Gales, J. A.

    2017-12-01

    The Monterey Coordinated Canyon Experiment (CCE) deployed an array of instruments along the Monterey Canyon floor to characterize the structure, velocity and frequency of sediment flows. CCE utilized novel technologies developed at MBARI to capture sediment flow data in unprecedented detail. 1. The Seafloor Instrument Node (SIN) at 1850 meters depth housed 3 ADCPs at 3 different frequencies, CTD, current meter, oxygen optode, fluorometer/backscatter sensor, and logged data at 10 second intervals or faster. The SIN included an acoustic modem for communication with shore through a Wave Glider relay, and provided high-resolution measurements of three flow events during three successive deployments over 1.5 years. 2. Beachball-sized Benthic Event Detectors (BEDs) were deployed on or under the seafloor to measure the characteristics of sediment density flows. Each BED recorded data from a pressure sensor and a 3-axis accelerometer and gyro to characterize motions during transport events (e.g. tumble vs rotation). An acoustic modem capable of operating through more than a meter of sediment enabled communications with a ship or autonomous surface vehicle. Multiple BEDs were deployed at various depths in the canyon during CCE, detecting and measuring many transport events; one BED moved 9 km down canyon in 50 minutes during one event. 3. Wave Glider Hot Spot (HS), equipped with acoustic and RF modems, acted as data relay between SIN, BEDs and shore, and acoustically located BEDs after sediment density flows.. In some cases HS relayed BED motion data to shore within a few hours of the event. HS provided an acoustic console to the SIN, allowing shore-based users to check SIN health and status, perform maintenance, etc. 4. Mapping operations were conducted 4 times at the SIN site to quantify depositional and erosional patterns, utilizing a prototype ultra-high-resolution mapping system on the ROV Doc Ricketts. The system consists of a 400-kHz Reson 7125 multibeam sonar, a 3

  14. Genome sequence of foxtail millet (Setaria italica) provides insights into grass evolution and biofuel potential.

    Science.gov (United States)

    Zhang, Gengyun; Liu, Xin; Quan, Zhiwu; Cheng, Shifeng; Xu, Xun; Pan, Shengkai; Xie, Min; Zeng, Peng; Yue, Zhen; Wang, Wenliang; Tao, Ye; Bian, Chao; Han, Changlei; Xia, Qiuju; Peng, Xiaohua; Cao, Rui; Yang, Xinhua; Zhan, Dongliang; Hu, Jingchu; Zhang, Yinxin; Li, Henan; Li, Hua; Li, Ning; Wang, Junyi; Wang, Chanchan; Wang, Renyi; Guo, Tao; Cai, Yanjie; Liu, Chengzhang; Xiang, Haitao; Shi, Qiuxiang; Huang, Ping; Chen, Qingchun; Li, Yingrui; Wang, Jun; Zhao, Zhihai; Wang, Jian

    2012-05-13

    Foxtail millet (Setaria italica), a member of the Poaceae grass family, is an important food and fodder crop in arid regions and has potential for use as a C(4) biofuel. It is a model system for other biofuel grasses, including switchgrass and pearl millet. We produced a draft genome (∼423 Mb) anchored onto nine chromosomes and annotated 38,801 genes. Key chromosome reshuffling events were detected through collinearity identification between foxtail millet, rice and sorghum including two reshuffling events fusing rice chromosomes 7 and 9, 3 and 10 to foxtail millet chromosomes 2 and 9, respectively, that occurred after the divergence of foxtail millet and rice, and a single reshuffling event fusing rice chromosome 5 and 12 to foxtail millet chromosome 3 that occurred after the divergence of millet and sorghum. Rearrangements in the C(4) photosynthesis pathway were also identified.

  15. Molecular taxonomy provides new insights into anopheles species of the neotropical arribalzagia series.

    Directory of Open Access Journals (Sweden)

    Giovan F Gómez

    Full Text Available Phylogenetic analysis of partial mitochondrial cytochrome oxidase c subunit I (COI and nuclear internal transcribed spacer 2 (ITS2 sequences were used to evaluate initial identification and to investigate phylogenetic relationships of seven Anopheles morphospecies of the Arribalzagia Series from Colombia. Phylogenetic trees recovered highly supported clades for An. punctimaculas.s., An. calderoni, An. malefactor s.l., An. neomaculipalpus, An. apicimacula s.l., An. mattogrossensis and An. peryassui. This study provides the first molecular confirmation of An. malefactorfrom Colombia and discovered conflicting patterns of divergence for the molecular markers among specimens from northeast and northern Colombia suggesting the presence of two previously unrecognized Molecular Operational Taxonomic Units (MOTUs. Furthermore, two highly differentiated An. apicimacula MOTUs previously found in Panama were detected. Overall, the combined molecular dataset facilitated the detection of known and new Colombian evolutionary lineages, and constitutes the baseline for future research on their bionomics, ecology and potential role as malaria vectors.

  16. Barriers to Providing Health Education During Primary Care Visits at Community Health Centers: Clinical Staff Insights.

    Science.gov (United States)

    Alicea-Planas, Jessica; Pose, Alix; Smith, Linda

    2016-04-01

    The rapid increase of diverse patients living in the US has created a different set of needs in healthcare, with the persistence of health disparities continuing to challenge the current system. Chronic disease management has been discussed as a way to improve health outcomes, with quality patient education being a key component. Using a community based participatory research framework, this study utilized a web-based survey and explored clinical staff perceptions of barriers to providing patient education during primary care visits. With a response rate of nearly 42 %, appointment time allotment seemed to be one of the most critical factors related to the delivery of health education and should be considered key. The importance of team-based care and staff training were also significant. Various suggestions were made in order to improve the delivery of quality patient education at community health centers located in underserved areas.

  17. The ASCO Oncology Composite Provider Utilization File: New Data, New Insights.

    Science.gov (United States)

    Barr, Thomas R; Towle, Elaine L; Barr, Thomas R; Towle, Elaine L

    2016-01-01

    As we seek to understand the changing practice environment in oncology, the need for accurate information about demand for services, distribution of the delivery system in this sector of the health economy, and other practice trends is apparent. In this article, we present analysis of the sector using one of the public use files from the Centers for Medicare & Medicaid Services in combination with other publicly available data. Medicare data are particularly useful for this analysis because cancer is associated with aging and Medicare is the primary payer in the United States for patients older than age 65. As a result, nearly all oncologists who serve adult populations are represented in these data. By combining publicly available datasets into what we call the ASCO Provider Utilization File,we can investigate a wide range of supply, demand, and practice issues. We calculate the average work performed per physician, observe regional differences in work production,and quantify the downside risk and upside potential associated with the provision of chemotherapy drugs. Comparing the supply of oncologists by state with physician work relative value units and with estimates of cancer incidence by state reveals intriguing differences in the distribution of physicians and the demand for oncology services. In addition, our analysis demonstrates significant downside practice risk associated with the provision of drug therapy to Medicare beneficiaries. The economic risk associated with the purchase and delivery of chemotherapy is of particular concern as pressure for value increases. This article provides a description of a new dataset and interesting observations from these data.

  18. Ancient DNA provides new insight into the maternal lineages and domestication of Chinese donkeys.

    Science.gov (United States)

    Han, Lu; Zhu, Songbiao; Ning, Chao; Cai, Dawei; Wang, Kai; Chen, Quanjia; Hu, Songmei; Yang, Junkai; Shao, Jing; Zhu, Hong; Zhou, Hui

    2014-11-30

    The donkey (Equus asinus) is an important domestic animal that provides a reliable source of protein and method of transportation for many human populations. However, the process of domestication and the dispersal routes of the Chinese donkey are still unclear, as donkey remains are sparse in the archaeological record and often confused with horse remains. To explore the maternal origins and dispersal route of Chinese donkeys, both mitochondrial DNA D-loop and cytochrome b gene fragments of 21 suspected donkey remains from four archaeological sites in China were amplified and sequenced. Molecular methods of species identification show that 17 specimens were donkeys and three samples had the maternal genetic signature of horses. One sample that dates to about 20,000 years before present failed to amplify. In this study, the phylogenetic analysis reveals that ancient Chinese donkeys have high mitochondrial DNA diversity and two distinct mitochondrial maternal lineages, known as the Somali and Nubian lineages. These results indicate that the maternal origin of Chinese domestic donkeys was probably related to the African wild ass, which includes the Nubian wild ass (Equus africanus africanus) and the Somali wild ass (Equus africanus somaliensis). Combined with historical records, the results of this study implied that domestic donkeys spread into west and north China before the emergence of the Han dynasty. The number of Chinese domestic donkeys had increased primarily to meet demand for the expansion of trade, and they were likely used as commodities or for shipping goods along the Silk Road during the Tang Dynasty, when the Silk Road reached its golden age. This study is the first to provide valuable ancient animal DNA evidence for early trade between African and Asian populations. The ancient DNA analysis of Chinese donkeys also sheds light on the dynamic process of the maternal origin, domestication, and dispersal route of ancient Chinese donkeys.

  19. Geophysical insights on the GIA process provided by high-quality constraints from peripheral regions: An outlook on perspectives from North America and from the Mediterranean basin

    Science.gov (United States)

    Roy, K.; Peltier, W. R.

    2017-12-01

    Our understanding of the Earth-Ice-Ocean interactions that have accompanied the large glaciation-deglaciation process characteristic of the last half of the Pleistocene has benefited significantly from the development of high-quality models of the Glacial Isostatic Adjustment (GIA) process. These models provide fundamental insight on the large changes in sea level and land ice cover over this time period, as well as key constraints on the viscosity structure of the Earth's interior. Their development has benefited from the recent availability of high-quality constraints from regions of forebulge collapse. In particular, over North America, the joint use of high-quality sea level data from the U.S. East coast, together with the vast network of precise space-geodetic observations of crustal motion existing over most of the interior of the continent, has led to the latest ICE-7G_NA (VM7) model (Roy & Peltier, GJI, 2017). In this paper, exciting opportunities provided by such high-quality observations related to the GIA process will be discussed, not only in the context of the continuing effort to refine global models of this phenomenon, but also in terms of the fundamental insight they may provide on outstanding issues in high-pressure geophysics, paleoclimatology or hydrogeology. Specific examples where such high-quality observations can be used (either separately, or using a combination of independent sources) will be presented, focusing particularly on constraints from the North American continent and from the Mediterranean basin. This work will demonstrate that, given the high-quality of currently available constraints on the GIA process, considerable further geophysical insight can be obtained based upon the use of spherically-symmetric models of the viscosity structure of the planet.

  20. Rheo-NMR - how nuclear magnetic resonance is providing new insight regarding complex fluid rheology

    International Nuclear Information System (INIS)

    Callaghan, P.T.

    2000-01-01

    Over the past five decades, NMR has revolutionised chemistry, and has found widespread application in condensed matter physics, in molecular biology, in medicine and in food technology. Most recently NMR has made a significant impact in chemical engineering, where it is being extensively used for the non-invasive study of dispersion and flow in porous media. One of the most recent applications of NMR in materials science concerns its use in the study of the mechanical properties of complex fluids. This particular aspect of NMR has been extensively developed in research carried out at Massey University in New Zealand. In this short article, some of the ideas behind this work and the applications which have resulted, will be described. These examples provide a glimpse of possible applications of Nuclear Magnetic Resonance to the study of complex fluid rheology. While this is a very new field of research in which only a handful of groups presently participate, the potential exists for a substantial increase in Rheo-NMR research activity. Systems studied to date include polymer melts and semi-dilute solutions, thermotropic and lyotropic liquid crystals and liquid crystalline polymers, micellar solutions, food materials and colloidal suspensions. Rheo-NMR suffers in a number of respects by comparison with optical methods. It is expensive, it is difficult to use, it suffers from poor signal-to-noise ratios and the effective interpretation of spectra often depends on familiarity with the nuclear spin Hamiltonian and the associated effects of spin dynamics. Nonetheless NMR offers some unique advantages, including the ability to work with opaque materials, the ability to combine velocimetry with localised spectroscopy, and the ability to access a wide range of molecular properties relating to organisation, orientation and dynamics. Rheo-NMR has been able to provide a direct window on a variety of behaviours, including slip, shear-thinning, shear banding, yield stress

  1. Renal blood flow dynamics in inbred rat strains provides insight into autoregulation.

    Science.gov (United States)

    A Mitrou, Nicholas G; Cupples, William A

    2014-01-01

    Renal autoregulation maintains stable renal blood flow in the face of constantly fluctuating blood pressure. Autoregulation is also the only mechanism that protects the delicate glomerular capillaries when blood pressure increases. In order to understand autoregulation, the renal blood flow response to changing blood pressure is studied. The steadystate response of blood flow is informative, but limits investigation of the individual mechanisms of autoregulation. The dynamics of autoregulation can be probed with transfer function analysis. The frequency-domain analysis of autoregulation allows investigators to probe the relative activity of each mechanism of autoregulation. We discuss the methodology and interpretation of transfer function analysis. Autoregulation is routinely studied in the rat, of which there are many inbred strains. There are multiple strains of rat that are either selected or inbred as models of human pathology. We discuss relevant characteristics of Brown Norway, Spontaneously hypertensive, Dahl, and Fawn-Hooded hypertensive rats and explore differences among these strains in blood pressure, dynamic autoregulation, and susceptibility to hypertensive renal injury. Finally we show that the use of transfer function analysis in these rat strains has contributed to our understanding of the physiology and pathophysiology of autoregulation and hypertensive renal disease.Interestingly all these strains demonstrate effective tubuloglomerular feedback suggesting that this mechanism is not sufficient for effective autoregulation. In contrast, obligatory or conditional failure of the myogenic mechanism suggests that this component is both necessary and sufficient for autoregulation.

  2. Systems Factorial Technology provides new insights on global-local information processing in autism spectrum disorders.

    Science.gov (United States)

    Johnson, Shannon A; Blaha, Leslie M; Houpt, Joseph W; Townsend, James T

    2010-02-01

    Previous studies of global-local processing in autism spectrum disorders (ASDs) have indicated mixed findings, with some evidence of a local processing bias, or preference for detail-level information, and other results suggesting typical global advantage, or preference for the whole or gestalt. Findings resulting from this paradigm have been used to argue for or against a detail focused processing bias in ASDs, and thus have important theoretical implications. We applied Systems Factorial Technology, and the associated Double Factorial Paradigm (both defined in the text), to examine information processing characteristics during a divided attention global-local task in high-functioning individuals with an ASD and typically developing controls. Group data revealed global advantage for both groups, contrary to some current theories of ASDs. Information processing models applied to each participant revealed that task performance, although showing no differences at the group level, was supported by different cognitive mechanisms in ASD participants compared to controls. All control participants demonstrated inhibitory parallel processing and the majority demonstrated a minimum-time stopping rule. In contrast, ASD participants showed exhaustive parallel processing with mild facilitatory interactions between global and local information. Thus our results indicate fundamental differences in the stopping rules and channel dependencies in individuals with an ASD.

  3. Genome analysis of Hibiscus syriacus provides insights of polyploidization and indeterminate flowering in woody plants.

    Science.gov (United States)

    Kim, Yong-Min; Kim, Seungill; Koo, Namjin; Shin, Ah-Young; Yeom, Seon-In; Seo, Eunyoung; Park, Seong-Jin; Kang, Won-Hee; Kim, Myung-Shin; Park, Jieun; Jang, Insu; Kim, Pan-Gyu; Byeon, Iksu; Kim, Min-Seo; Choi, JinHyuk; Ko, Gunhwan; Hwang, JiHye; Yang, Tae-Jin; Choi, Sang-Bong; Lee, Je Min; Lim, Ki-Byung; Lee, Jungho; Choi, Ik-Young; Park, Beom-Seok; Kwon, Suk-Yoon; Choi, Doil; Kim, Ryan W

    2017-02-01

    Hibiscus syriacus (L.) (rose of Sharon) is one of the most widespread garden shrubs in the world. We report a draft of the H. syriacus genome comprised of a 1.75 Gb assembly that covers 92% of the genome with only 1.7% (33 Mb) gap sequences. Predicted gene modeling detected 87,603 genes, mostly supported by deep RNA sequencing data. To define gene family distribution among relatives of H. syriacus, orthologous gene sets containing 164,660 genes in 21,472 clusters were identified by OrthoMCL analysis of five plant species, including H. syriacus, Arabidopsis thaliana, Gossypium raimondii, Theobroma cacao and Amborella trichopoda. We inferred their evolutionary relationships based on divergence times among Malvaceae plant genes and found that gene families involved in flowering regulation and disease resistance were more highly divergent and expanded in H. syriacus than in its close relatives, G. raimondii (DD) and T. cacao. Clustered gene families and gene collinearity analysis revealed that two recent rounds of whole-genome duplication were followed by diploidization of the H. syriacus genome after speciation. Copy number variation and phylogenetic divergence indicates that WGDs and subsequent diploidization led to unequal duplication and deletion of flowering-related genes in H. syriacus and may affect its unique floral morphology. © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  4. Construction patterns of birds’ nests provide insight into nest-building behaviours

    Directory of Open Access Journals (Sweden)

    Lucia Biddle

    2017-02-01

    Full Text Available Previous studies have suggested that birds and mammals select materials needed for nest building based on their thermal or structural properties, although the amounts or properties of the materials used have been recorded for only a very small number of species. Some of the behaviours underlying the construction of nests can be indirectly determined by careful deconstruction of the structure and measurement of the biomechanical properties of the materials used. Here we examined this idea in an investigation of Bullfinch (Pyrrhula pyrrhula nests as a model for open-nesting songbird species that construct a “twig” nest, and tested the hypothesis that materials in different parts of nests serve different functions. The quantities of materials present in the nest base, sides and cup were recorded before structural analysis. Structural analysis showed that the base of the outer nests were composed of significantly thicker, stronger and more rigid materials compared to the side walls, which in turn were significantly thicker, stronger and more rigid than materials used in the cup. These results suggest that the placement of particular materials in nests may not be random, but further work is required to determine if the final structure of a nest accurately reflects the construction process.

  5. Construction patterns of birds’ nests provide insight into nest-building behaviours

    Science.gov (United States)

    Goodman, Adrian M.

    2017-01-01

    Previous studies have suggested that birds and mammals select materials needed for nest building based on their thermal or structural properties, although the amounts or properties of the materials used have been recorded for only a very small number of species. Some of the behaviours underlying the construction of nests can be indirectly determined by careful deconstruction of the structure and measurement of the biomechanical properties of the materials used. Here we examined this idea in an investigation of Bullfinch (Pyrrhula pyrrhula) nests as a model for open-nesting songbird species that construct a “twig” nest, and tested the hypothesis that materials in different parts of nests serve different functions. The quantities of materials present in the nest base, sides and cup were recorded before structural analysis. Structural analysis showed that the base of the outer nests were composed of significantly thicker, stronger and more rigid materials compared to the side walls, which in turn were significantly thicker, stronger and more rigid than materials used in the cup. These results suggest that the placement of particular materials in nests may not be random, but further work is required to determine if the final structure of a nest accurately reflects the construction process. PMID:28265501

  6. Construction patterns of birds' nests provide insight into nest-building behaviours.

    Science.gov (United States)

    Biddle, Lucia; Goodman, Adrian M; Deeming, D Charles

    2017-01-01

    Previous studies have suggested that birds and mammals select materials needed for nest building based on their thermal or structural properties, although the amounts or properties of the materials used have been recorded for only a very small number of species. Some of the behaviours underlying the construction of nests can be indirectly determined by careful deconstruction of the structure and measurement of the biomechanical properties of the materials used. Here we examined this idea in an investigation of Bullfinch ( Pyrrhula pyrrhula ) nests as a model for open-nesting songbird species that construct a "twig" nest, and tested the hypothesis that materials in different parts of nests serve different functions. The quantities of materials present in the nest base, sides and cup were recorded before structural analysis. Structural analysis showed that the base of the outer nests were composed of significantly thicker, stronger and more rigid materials compared to the side walls, which in turn were significantly thicker, stronger and more rigid than materials used in the cup. These results suggest that the placement of particular materials in nests may not be random, but further work is required to determine if the final structure of a nest accurately reflects the construction process.

  7. Linkage Map of Lissotriton Newts Provides Insight into the Genetic Basis of Reproductive Isolation

    Directory of Open Access Journals (Sweden)

    Marta Niedzicka

    2017-07-01

    Full Text Available Linkage maps are widely used to investigate structure, function, and evolution of genomes. In speciation research, maps facilitate the study of the genetic architecture of reproductive isolation by allowing identification of genomic regions underlying reduced fitness of hybrids. Here we present a linkage map for European newts of the Lissotriton vulgaris species complex, constructed using two families of F2 L. montandoni × L. vulgaris hybrids. The map consists of 1146 protein-coding genes on 12 linkage groups, equal to the haploid chromosome number, with a total length of 1484 cM (1.29 cM per marker. It is notably shorter than two other maps available for salamanders, but the differences in map length are consistent with cytogenetic estimates of the number of chiasmata per chromosomal arm. Thus, large salamander genomes do not necessarily translate into long linkage maps, as previously suggested. Consequently, salamanders are an excellent model to study evolutionary consequences of recombination rate variation in taxa with large genomes and a similar number of chromosomes. A complex pattern of transmission ratio distortion (TRD was detected: TRD occurred mostly in one family, in one breeding season, and was clustered in two genomic segments. This is consistent with environment-dependent mortality of individuals carrying L. montandoni alleles in these two segments and suggests a role of TRD blocks in reproductive isolation. The reported linkage map will empower studies on the genomic architecture of divergence and interactions between the genomes of hybridizing newts.

  8. The Ditylenchus destructor genome provides new insights into the evolution of plant parasitic nematodes.

    Science.gov (United States)

    Zheng, Jinshui; Peng, Donghai; Chen, Ling; Liu, Hualin; Chen, Feng; Xu, Mengci; Ju, Shouyong; Ruan, Lifang; Sun, Ming

    2016-07-27

    Plant-parasitic nematodes were found in 4 of the 12 clades of phylum Nematoda. These nematodes in different clades may have originated independently from their free-living fungivorous ancestors. However, the exact evolutionary process of these parasites is unclear. Here, we sequenced the genome sequence of a migratory plant nematode, Ditylenchus destructor We performed comparative genomics among the free-living nematode, Caenorhabditis elegans and all the plant nematodes with genome sequences available. We found that, compared with C. elegans, the core developmental control processes underwent heavy reduction, though most signal transduction pathways were conserved. We also found D. destructor contained more homologies of the key genes in the above processes than the other plant nematodes. We suggest that Ditylenchus spp. may be an intermediate evolutionary history stage from free-living nematodes that feed on fungi to obligate plant-parasitic nematodes. Based on the facts that D. destructor can feed on fungi and has a relatively short life cycle, and that it has similar features to both C. elegans and sedentary plant-parasitic nematodes from clade 12, we propose it as a new model to study the biology, biocontrol of plant nematodes and the interaction between nematodes and plants. © 2016 The Author(s).

  9. Comparative genomics provides insights into the lifestyle and reveals functional heterogeneity of dark septate endophytic fungi.

    Science.gov (United States)

    Knapp, Dániel G; Németh, Julianna B; Barry, Kerrie; Hainaut, Matthieu; Henrissat, Bernard; Johnson, Jenifer; Kuo, Alan; Lim, Joanne Hui Ping; Lipzen, Anna; Nolan, Matt; Ohm, Robin A; Tamás, László; Grigoriev, Igor V; Spatafora, Joseph W; Nagy, László G; Kovács, Gábor M

    2018-04-20

    Dark septate endophytes (DSE) are a form-group of root endophytic fungi with elusive functions. Here, the genomes of two common DSE of semiarid areas, Cadophora sp. and Periconia macrospinosa were sequenced and analyzed with another 32 ascomycetes of different lifestyles. Cadophora sp. (Helotiales) and P. macrospinosa (Pleosporales) have genomes of 70.46 Mb and 54.99 Mb with 22,766 and 18,750 gene models, respectively. The majority of DSE-specific protein clusters lack functional annotation with no similarity to characterized proteins, implying that they have evolved unique genetic innovations. Both DSE possess an expanded number of carbohydrate active enzymes (CAZymes), including plant cell wall degrading enzymes (PCWDEs). Those were similar in three other DSE, and contributed a signal for the separation of root endophytes in principal component analyses of CAZymes, indicating shared genomic traits of DSE fungi. Number of secreted proteases and lipases, aquaporins, and genes linked to melanin synthesis were also relatively high in our fungi. In spite of certain similarities between our two DSE, we observed low levels of convergence in their gene family evolution. This suggests that, despite originating from the same habitat, these two fungi evolved along different evolutionary trajectories and display considerable functional differences within the endophytic lifestyle.

  10. Historical ecology provides new insights for ecosystem management: Eastern Baltic cod case study

    DEFF Research Database (Denmark)

    MacKenzie, Brian; Ojaveer, Henn; Eero, Margit

    2011-01-01

    A recent historical marine ecological case study (cod in the eastern Baltic Sea) is used to show how long-term data and knowledge of fluctuations can contribute to revisions of fishery management policy. The case study first developed new longer analytical time series of spawner biomass and recru......A recent historical marine ecological case study (cod in the eastern Baltic Sea) is used to show how long-term data and knowledge of fluctuations can contribute to revisions of fishery management policy. The case study first developed new longer analytical time series of spawner biomass...... catch data from the late 1500s to early 1600s also contributed new perspectives to cod population dynamics under alternative ecosystem forcings. These new perspectives have contributed, and will likely continue to contribute to new management policies (e.g., revision of fishery management reference...... points), which should lead to higher sustainability of the population and fishery yields, and improved overall ecosystem health. These perspectives will likely continue to provide baseline information as ICES and the EU develop new policies based on maximum sustainable yield concepts....

  11. Heterochronic truncation of odontogenesis in theropod dinosaurs provides insight into the macroevolution of avian beaks

    Science.gov (United States)

    Stiegler, Josef; Wu, Ping; Chuong, Cheng-Ming; Hu, Dongyu; Balanoff, Amy; Zhou, Yachun; Xu, Xing

    2017-01-01

    Beaks are innovative structures characterizing numerous tetrapod lineages, including birds, but little is known about how developmental processes influenced the macroevolution of these important structures. Here we provide evidence of ontogenetic vestigialization of alveoli in two lineages of theropod dinosaurs and show that these are transitional phenotypes in the evolution of beaks. One of the smallest known caenagnathid oviraptorosaurs and a small specimen of the Early Cretaceous bird Sapeornis both possess shallow, empty vestiges of dentary alveoli. In both individuals, the system of vestiges connects via foramina with a dorsally closed canal homologous to alveoli. Similar morphologies are present in Limusaurus, a beaked theropod that becomes edentulous during ontogeny; and an analysis of neontological and paleontological evidence shows that ontogenetic reduction of the dentition is a relatively common phenomenon in vertebrate evolution. Based on these lines of evidence, we propose that progressively earlier postnatal and embryonic truncation of odontogenesis corresponds with expansion of rostral keratin associated with the caruncle, and these progenesis and peramorphosis heterochronies combine to drive the evolution of edentulous beaks in nonavian theropods and birds. Following initial apomorphic expansion of rostral keratinized epithelia in perinatal toothed theropods, beaks appear to inhibit odontogenesis as they grow postnatally, resulting in a sequence of common morphologies. This sequence is shifted earlier in development through phylogeny until dentition is absent at hatching, and odontogenesis is inhibited by beak formation in ovo. PMID:28973883

  12. Heterochronic truncation of odontogenesis in theropod dinosaurs provides insight into the macroevolution of avian beaks.

    Science.gov (United States)

    Wang, Shuo; Stiegler, Josef; Wu, Ping; Chuong, Cheng-Ming; Hu, Dongyu; Balanoff, Amy; Zhou, Yachun; Xu, Xing

    2017-10-10

    Beaks are innovative structures characterizing numerous tetrapod lineages, including birds, but little is known about how developmental processes influenced the macroevolution of these important structures. Here we provide evidence of ontogenetic vestigialization of alveoli in two lineages of theropod dinosaurs and show that these are transitional phenotypes in the evolution of beaks. One of the smallest known caenagnathid oviraptorosaurs and a small specimen of the Early Cretaceous bird Sapeornis both possess shallow, empty vestiges of dentary alveoli. In both individuals, the system of vestiges connects via foramina with a dorsally closed canal homologous to alveoli. Similar morphologies are present in Limusaurus , a beaked theropod that becomes edentulous during ontogeny; and an analysis of neontological and paleontological evidence shows that ontogenetic reduction of the dentition is a relatively common phenomenon in vertebrate evolution. Based on these lines of evidence, we propose that progressively earlier postnatal and embryonic truncation of odontogenesis corresponds with expansion of rostral keratin associated with the caruncle, and these progenesis and peramorphosis heterochronies combine to drive the evolution of edentulous beaks in nonavian theropods and birds. Following initial apomorphic expansion of rostral keratinized epithelia in perinatal toothed theropods, beaks appear to inhibit odontogenesis as they grow postnatally, resulting in a sequence of common morphologies. This sequence is shifted earlier in development through phylogeny until dentition is absent at hatching, and odontogenesis is inhibited by beak formation in ovo .

  13. Comparative exome sequencing of metastatic lesions provides insights into the mutational progression of melanoma

    Directory of Open Access Journals (Sweden)

    Gartner Jared J

    2012-09-01

    Full Text Available Abstract Background Metastasis is characterized by spreading of neoplastic cells to an organ other than where they originated and is the predominant cause of death among cancer patients. This holds true for melanoma, whose incidence is increasing more rapidly than any other cancer and once disseminated has few therapeutic options. Here we performed whole exome sequencing of two sets of matched normal and metastatic tumor DNAs. Results Using stringent criteria, we evaluated the similarities and differences between the lesions. We find that in both cases, 96% of the single nucleotide variants are shared between the two metastases indicating that clonal populations gave rise to the distant metastases. Analysis of copy number variation patterns of both metastatic sets revealed a trend similar to that seen with our single nucleotide variants. Analysis of pathway enrichment on tumor sets shows commonly mutated pathways enriched between individual sets of metastases and all metastases combined. Conclusions These data provide a proof-of-concept suggesting that individual metastases may have sufficient similarity for successful targeting of driver mutations.

  14. Molecular underpinnings of prefrontal cortex development in rodents provide insights into the etiology of neurodevelopmental disorders.

    Science.gov (United States)

    Schubert, D; Martens, G J M; Kolk, S M

    2015-07-01

    The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcription factors, guidance cues and other regulatory molecules and requires the intricate and temporal orchestration of a number of developmental processes. Disturbance or failure of any of these processes causing neurodevelopmental abnormalities within the PFC may contribute to several of the cognitive deficits seen in patients with neurodevelopmental disorders. In this review, we elaborate on the specific processes underlying prefrontal development, such as induction and patterning of the prefrontal area, proliferation, migration and axonal guidance of medial prefrontal progenitors, and their eventual efferent and afferent connections. We furthermore integrate for the first time the available knowledge from genome-wide studies that have revealed genes linked to neurodevelopmental disorders with experimental molecular evidence in rodents. The integrated data suggest that the pathogenic variants in the neurodevelopmental disorder-associated genes induce prefrontal cytoarchitectonical impairments. This enhances our understanding of the molecular mechanisms of prefrontal (mis)development underlying the four major neurodevelopmental disorders in humans, that is, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder and schizophrenia, and may thus provide clues for the development of novel therapies.

  15. Visualizing the Immune System: Providing Key Insights into HIV/SIV Infections

    Directory of Open Access Journals (Sweden)

    Jacob D. Estes

    2018-03-01

    Full Text Available Immunological inductive tissues, such as secondary lymphoid organs, are composed of distinct anatomical microenvironments for the generation of immune responses to pathogens and immunogens. These microenvironments are characterized by the compartmentalization of highly specialized immune and stromal cell populations, as well as the presence of a complex network of soluble factors and chemokines that direct the intra-tissue trafficking of naïve and effector cell populations. Imaging platforms have provided critical contextual information regarding the molecular and cellular interactions that orchestrate the spatial microanatomy of relevant cells and the development of immune responses against pathogens. Particularly in HIV/SIV disease, imaging technologies are of great importance in the investigation of the local interplay between the virus and host cells, with respect to understanding viral dynamics and persistence, immune responses (i.e., adaptive and innate inflammatory responses, tissue structure and pathologies, and changes to the surrounding milieu and function of immune cells. Merging imaging platforms with other cutting-edge technologies could lead to novel findings regarding the phenotype, function, and molecular signatures of particular immune cell targets, further promoting the development of new antiviral treatments and vaccination strategies.

  16. The genome sequence of the wild tomato Solanum pimpinellifolium provides insights into salinity tolerance

    KAUST Repository

    Razali, Rozaimi; Bougouffa, Salim; Morton, Mitchell J. L.; Lightfoot, Damien; Alam, Intikhab; Essack, Magbubah; Arold, Stefan T.; Kamau, Allan; Schmö ckel, Sandra M.; Pailles, Yveline; Shahid, Mohammed; Michell, Craig; Al-Babili, Salim; Ho, Yung Shwen; Tester, Mark A.; Bajic, Vladimir B.; Negrã o, Só nia

    2017-01-01

    Solanum pimpinellifolium, a wild relative of cultivated tomato, offers a wealth of breeding potential for several desirable traits such as tolerance to abiotic and biotic stresses. Here, we report the genome and annotation of S. pimpinellifolium LA0480. The LA0480 genome size (811 Mb) and the number of annotated genes (25,970) are within the range observed for other sequenced tomato species. We developed and utilized the Dragon Eukaryotic Analyses Platform (DEAP) to functionally annotate the LA0480 protein-coding genes. Additionally, we used DEAP to compare protein function between S. pimpinellifolium and cultivated tomato. Our data suggest enrichment in genes involved in biotic and abiotic stress responses. Moreover, we present phenotypic data from one field experiment that demonstrate a greater salinity tolerance for fruit- and yield-related traits in S. pimpinellifolium compared with cultivated tomato. To understand the genomic basis for these differences in S. pimpinellifolium and S. lycopersicum, we analyzed 15 genes that have previously been shown to mediate salinity tolerance in plants. We show that S. pimpinellifolium has a higher copy number of the inositol-3-phosphate synthase and phosphatase genes, which are both key enzymes in the production of inositol and its derivatives. Moreover, our analysis indicates that changes occurring in the inositol phosphate pathway may contribute to the observed higher salinity tolerance in LA0480. Altogether, our work provides essential resources to understand and unlock the genetic and breeding potential of S. pimpinellifolium, and to discover the genomic basis underlying its environmental robustness.

  17. Chlorophyll fluorescence lifetime imaging provides new insight into the chlorosis induced by plant virus infection.

    Science.gov (United States)

    Lei, Rong; Jiang, Hongshan; Hu, Fan; Yan, Jin; Zhu, Shuifang

    2017-02-01

    Leaf chlorosis induced by plant virus infection has a short fluorescence lifetime, which reflects damaged photosynthetic complexes and degraded chloroplasts. Plant viruses often induce chlorosis and necrosis, which are intimately related to photosynthetic functions. Chlorophyll fluorescence lifetime measurement is a valuable noninvasive tool for analyzing photosynthetic processes and is a sensitive indicator of the environment surrounding the fluorescent molecules. In this study, our central goal was to explore the effect of viral infection on photosynthesis by employing chlorophyll fluorescence lifetime imaging (FLIM), steady-state fluorescence, non-photochemical quenching (NPQ), transmission electron microscopy (TEM), and pigment analysis. The data indicated that the chlorophyll fluorescence lifetime of chlorotic leaves was significantly shorter than that of healthy control leaves, and the fitted short lifetime component of chlorophyll fluorescence of chlorotic leaves was dominant. This dominant short lifetime component may result from damage to the structure of thylakoid, which was confirmed by TEM. The NPQ value of chlorotic leaves was slightly higher than that of healthy green leaves, which can be explained by increased neoxanthin, lutein and violaxanthin content relative to chlorophyll a. The difference in NPQ is slight, but FLIM can provide simple and direct characterization of PSII structure and photosynthetic function. Therefore, this technique shows great potential as a simple and rapid method for studying mechanisms of plant virus infection.

  18. Ancient DNA from Nubian and Somali wild ass provides insights into donkey ancestry and domestication.

    Science.gov (United States)

    Kimura, Birgitta; Marshall, Fiona B; Chen, Shanyuan; Rosenbom, Sónia; Moehlman, Patricia D; Tuross, Noreen; Sabin, Richard C; Peters, Joris; Barich, Barbara; Yohannes, Hagos; Kebede, Fanuel; Teclai, Redae; Beja-Pereira, Albano; Mulligan, Connie J

    2011-01-07

    Genetic data from extant donkeys (Equus asinus) have revealed two distinct mitochondrial DNA haplogroups, suggestive of two separate domestication events in northeast Africa about 5000 years ago. Without distinct phylogeographic structure in domestic donkey haplogroups and with little information on the genetic makeup of the ancestral African wild ass, however, it has been difficult to identify wild ancestors and geographical origins for the domestic mitochondrial clades. Our analysis of ancient archaeological and historic museum samples provides the first genetic information on the historic Nubian wild ass (Equus africanus africanus), Somali wild ass (Equus africanus somaliensis) and ancient donkey. The results demonstrate that the Nubian wild ass was an ancestor of the first donkey haplogroup. In contrast, the Somali wild ass has considerable mitochondrial divergence from the Nubian wild ass and domestic donkeys. These findings resolve the long-standing issue of the role of the Nubian wild ass in the domestication of the donkey, but raise new questions regarding the second ancestor for the donkey. Our results illustrate the complexity of animal domestication, and have conservation implications for critically endangered Nubian and Somali wild ass.

  19. Transgenerational endpoints provide increased sensitivity and insight into multigenerational responses of Lymnaea stagnalis exposed to cadmium.

    Science.gov (United States)

    Reátegui-Zirena, Evelyn G; Fidder, Bridgette N; Olson, Adric D; Dawson, Daniel E; Bilbo, Thomas R; Salice, Christopher J

    2017-05-01

    Ecotoxicology provides data to inform environmental management. Many testing protocols do not consider offspring fitness and toxicant sensitivity. Cadmium (Cd) is a well-studied and ubiquitous toxicant but little is known about the effects on offspring of exposed parents (transgenerational effects). This study had three objectives: to identify endpoints related to offspring performance; to determine whether parental effects would manifest as a change in Cd tolerance in offspring and how parental exposure duration influenced the manifestation of parental effects. Adult snails were exposed to Cd 0, 25, 50, 100, 200 and 400 μg Cd/L for eight weeks. There were effects on adult endpoints (e.g., growth, reproduction) but only at the highest concentrations (>100 μg/L). Alternatively, we observed significant transgenerational effects at all Cd concentrations. Surprisingly, we found increased Cd tolerance in hatchlings from all parental Cd exposure concentrations even though eggs and hatchlings were in Cd-free conditions for 6 weeks. Explicit consideration of offspring performance adds value to current toxicity testing protocols. Parental exposure duration has important implications for offspring effects and that contaminant concentrations that are not directly toxic to parents can cause transgenerational changes in resistance that have significant implications for toxicity testing and adaptive responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. In vitro analysis of RQC activities provides insights into the mechanism and function of CAT tailing

    Science.gov (United States)

    Osuna, Beatriz A; Howard, Conor J; KC, Subheksha; Frost, Adam; Weinberg, David E

    2017-01-01

    Ribosomes can stall during translation due to defects in the mRNA template or translation machinery, leading to the production of incomplete proteins. The Ribosome-associated Quality control Complex (RQC) engages stalled ribosomes and targets nascent polypeptides for proteasomal degradation. However, how each RQC component contributes to this process remains unclear. Here we demonstrate that key RQC activities—Ltn1p-dependent ubiquitination and Rqc2p-mediated Carboxy-terminal Alanine and Threonine (CAT) tail elongation—can be recapitulated in vitro with a yeast cell-free system. Using this approach, we determined that CAT tailing is mechanistically distinct from canonical translation, that Ltn1p-mediated ubiquitination depends on the poorly characterized RQC component Rqc1p, and that the process of CAT tailing enables robust ubiquitination of the nascent polypeptide. These findings establish a novel system to study the RQC and provide a framework for understanding how RQC factors coordinate their activities to facilitate clearance of incompletely synthesized proteins. DOI: http://dx.doi.org/10.7554/eLife.27949.001 PMID:28718767

  1. Comparative proteomics in alkaptonuria provides insights into inflammation and oxidative stress.

    Science.gov (United States)

    Braconi, Daniela; Bernardini, Giulia; Paffetti, Alessandro; Millucci, Lia; Geminiani, Michela; Laschi, Marcella; Frediani, Bruno; Marzocchi, Barbara; Santucci, Annalisa

    2016-12-01

    Alkaptonuria (AKU) is an ultra-rare inborn error of metabolism associated with a defective catabolism of phenylalanine and tyrosine leading to increased systemic levels of homogentisic acid (HGA). Excess HGA is partly excreted in the urine, partly accumulated within the body and deposited onto connective tissues under the form of an ochronotic pigment, leading to a range of clinical manifestations. No clear genotype/phenotype correlation was found in AKU, and today there is the urgent need to identify biomarkers able to monitor AKU progression and evaluate response to treatment. With this aim, we provided the first proteomic study on serum and plasma samples from alkaptonuric individuals showing pathological SAA, CRP and Advanced Oxidation Protein Products (AOPP) levels. Interesting similarities with proteomic studies on other rheumatic diseases were highlighted together with proteome alterations supporting the existence of oxidative stress and inflammation in AKU. Potential candidate biomarkers to assess disease severity, monitor disease progression and evaluate response to treatment were identified as well. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. A Comprehensive Genome Survey Provides Novel Insights into Bile Salt Hydrolase (BSH in Lactobacillaceae

    Directory of Open Access Journals (Sweden)

    Lifeng Liang

    2018-05-01

    Full Text Available Bile salt hydrolase (BSH is a well-known enzyme that has been commonly characterized in probiotic bacteria, as it has cholesterol-lowering effects. However, its molecular investigations are scarce. Here, we build a local database of BSH sequences from Lactobacillaceae (BSH–SDL, and phylogenetic analysis and homology searches were employed to elucidate their comparability and distinctiveness among species. Evolutionary study demonstrates that BSH sequences in BSH–SDL are divided into five groups, named BSH A, B, C, D and E here, which can be the genetic basis for BSH classification and nomenclature. Sequence analysis suggests the differences between BSH-active and BSH-inactive proteins clearly, especially on site 82. In addition, a total of 551 BSHs from 107 species are identified from 451 genomes of 158 Lactobacillaceae species. Interestingly, those bacteria carrying various copies of BSH A or B can be predicted to be potential cholesterol-lowering probiotics, based on the results of phylogenetic analysis and the subtypes that those previously reported BSH-active probiotics possess. In summary, this study elaborates the molecular basis of BSH in Lactobacillaceae systematically, and provides a novel methodology as well as a consistent standard for the identification of the BSH subtype. We believe that high-throughput screening can be efficiently applied to the selection of promising candidate BSH-active probiotics, which will advance the development of healthcare products in cholesterol metabolism.

  3. Crystal Structure of the Herpesvirus Nuclear Egress Complex Provides Insights into Inner Nuclear Membrane Remodeling

    Directory of Open Access Journals (Sweden)

    Tzviya Zeev-Ben-Mordehai

    2015-12-01

    Full Text Available Although nucleo-cytoplasmic transport is typically mediated through nuclear pore complexes, herpesvirus capsids exit the nucleus via a unique vesicular pathway. Together, the conserved herpesvirus proteins pUL31 and pUL34 form the heterodimeric nuclear egress complex (NEC, which, in turn, mediates the formation of tight-fitting membrane vesicles around capsids at the inner nuclear membrane. Here, we present the crystal structure of the pseudorabies virus NEC. The structure revealed that a zinc finger motif in pUL31 and an extensive interaction network between the two proteins stabilize the complex. Comprehensive mutational analyses, characterized both in situ and in vitro, indicated that the interaction network is not redundant but rather complementary. Fitting of the NEC crystal structure into the recently determined cryoEM-derived hexagonal lattice, formed in situ by pUL31 and pUL34, provided details on the molecular basis of NEC coat formation and inner nuclear membrane remodeling.

  4. The genome sequence of the wild tomato Solanum pimpinellifolium provides insights into salinity tolerance

    KAUST Repository

    Razali, Rozaimi

    2017-11-14

    Solanum pimpinellifolium, a wild relative of cultivated tomato, offers a wealth of breeding potential for several desirable traits such as tolerance to abiotic and biotic stresses. Here, we report the genome and annotation of S. pimpinellifolium LA0480. The LA0480 genome size (811 Mb) and the number of annotated genes (25,970) are within the range observed for other sequenced tomato species. We developed and utilized the Dragon Eukaryotic Analyses Platform (DEAP) to functionally annotate the LA0480 protein-coding genes. Additionally, we used DEAP to compare protein function between S. pimpinellifolium and cultivated tomato. Our data suggest enrichment in genes involved in biotic and abiotic stress responses. Moreover, we present phenotypic data from one field experiment that demonstrate a greater salinity tolerance for fruit- and yield-related traits in S. pimpinellifolium compared with cultivated tomato. To understand the genomic basis for these differences in S. pimpinellifolium and S. lycopersicum, we analyzed 15 genes that have previously been shown to mediate salinity tolerance in plants. We show that S. pimpinellifolium has a higher copy number of the inositol-3-phosphate synthase and phosphatase genes, which are both key enzymes in the production of inositol and its derivatives. Moreover, our analysis indicates that changes occurring in the inositol phosphate pathway may contribute to the observed higher salinity tolerance in LA0480. Altogether, our work provides essential resources to understand and unlock the genetic and breeding potential of S. pimpinellifolium, and to discover the genomic basis underlying its environmental robustness.

  5. Weird mammals provide insights into the evolution of mammalian sex chromosomes and dosage compensation.

    Science.gov (United States)

    Graves, Jennifer A Marshall

    2015-12-01

    The deep divergence of mammalian groups 166 and 190 million years ago (MYA) provide genetic variation to explore the evolution of DNA sequence, gene arrangement and regulation of gene expression in mammals. With encouragement from the founder of the field, Mary Lyon, techniques in cytogenetics and molecular biology were progressively adapted to characterize the sex chromosomes of kangaroos and other marsupials, platypus and echidna-and weird rodent species. Comparative gene mapping reveals the process of sex chromosome evolution from their inception 190 MYA (they are autosomal in platypus) to their inevitable end (the Y has disappeared in two rodent lineages). Our X and Y are relatively young, getting their start with the evolution of the sex-determining SRY gene, which triggered progressive degradation of the Y chromosome. Even more recently, sex chromosomes of placental mammals fused with an autosomal region which now makes up most of the Y. Exploration of gene activity patterns over four decades showed that dosage compensation via X-chromosome inactivation is unique to therian mammals, and that this whole chromosome control process is different in marsupials and absent in monotremes and reptiles, and birds. These differences can be exploited to deduce how mammalian sex chromosomes and epigenetic silencing evolved.

  6. De Novo Assembly and Comparative Transcriptome Analysis Provide Insight into Lysine Biosynthesis in Toona sinensis Roem.

    Science.gov (United States)

    Zhang, Xia; Song, Zhenqiao; Liu, Tian; Guo, Linlin; Li, Xingfeng

    2016-01-01

    Toona sinensis Roem is a popular leafy vegetable in Chinese cuisine and is also used as a traditional Chinese medicine. In this study, leaf samples were collected from the same plant on two development stages and then used for high-throughput Illumina RNA-sequencing (RNA-Seq). 125,884 transcripts and 54,628 unigenes were obtained through de novo assembly. A total of 25,570 could be annotated with known biological functions, which indicated that the T. sinensis leaves and shoots were undergoing multiple developmental processes especially for active metabolic processes. Analysis of differentially expressed unigenes between the two libraries showed that the lysine biosynthesis was an enriched KEGG pathway, and candidate genes involved in the lysine biosynthesis pathway in T. sinensis leaves and shoots were identified. Our results provide a primary analysis of the gene expression files of T. sinensis leaf and shoot on different development stages and afford a valuable resource for genetic and genomic research on plant lysine biosynthesis.

  7. Systems analysis of transcriptional data provides insights into muscle's biological response to botulinum toxin.

    Science.gov (United States)

    Mukund, Kavitha; Mathewson, Margie; Minamoto, Viviane; Ward, Samuel R; Subramaniam, Shankar; Lieber, Richard L

    2014-11-01

    This study provides global transcriptomic profiling and analysis of botulinum toxin A (BoNT-A)-treated muscle over a 1-year period. Microarray analysis was performed on rat tibialis anterior muscles from 4 groups (n = 4/group) at 1, 4, 12, and 52 weeks after BoNT-A injection compared with saline-injected rats at 12 weeks. Dramatic transcriptional adaptation occurred at 1 week with a paradoxical increase in expression of slow and immature isoforms, activation of genes in competing pathways of repair and atrophy, impaired mitochondrial biogenesis, and increased metal ion imbalance. Adaptations of the basal lamina and fibrillar extracellular matrix (ECM) occurred by 4 weeks. The muscle transcriptome returned to its unperturbed state 12 weeks after injection. Acute transcriptional adaptations resemble denervated muscle with some subtle differences, but resolved more quickly compared with denervation. Overall, gene expression across time correlates with the generally accepted BoNT-A time course and suggests that the direct action of BoNT-A in skeletal muscle is relatively rapid. © 2014 Wiley Periodicals, Inc.

  8. Radiocarbon dating of American pika fecal pellets provides insights into population extirpations and climate refugia.

    Science.gov (United States)

    Millar, Constance I; Heckman, Katherine; Swanston, Christopher; Schmidt, Karena; Westfall, Robert D; Delany, Diane L

    The American pika (Ochotona princeps) has become a species of concern for its sensitivity to warm temperatures and potential vulnerability to global warming. We explored the value of radiocarbon dating of fecal pellets to address questions of population persistence and timing of site extirpation. Carbon was extracted from pellets collected at 43 locations in the western Great Basin, USA, including three known occupied sites and 40 sites of uncertain status at range margins or where previous studies indicated the species is vulnerable. We resolved calibrated dates with high precision (within several years), most of which fell in the period of the mid-late 20th century bomb curve. The two-sided nature of the bomb curve renders far- and near-side dates of equal probability, which are separated by one to four decades. We document methods for narrowing resolution to one age range, including stratigraphic analysis of vegetation collected from pika haypiles. No evidence was found for biases in atmospheric 14C levels due to fossil-derived or industrial CO2 contamination. Radiocarbon dating indicated that pellets can persist for >59 years; known occupied sites resolved contemporary dates. Using combined evidence from field observations and radiocarbon dating, and the Bodie Mountains as an example, we propose a historical biogeographic scenario for pikas in minor Great Basin mountain ranges adjacent to major cordillera, wherein historical climate variability led to cycles of extirpation and recolonization during alternating cool and warm centuries. Using this model to inform future dynamics for small ranges in biogeographic settings similar to the Bodie Mountains in California, extirpation of pikas appears highly likely under directional warming trends projected for the next century, even while populations in extensive cordillera (e.g., Sierra Nevada, Rocky Mountains, Cascade Range) are likely to remain viable due to extensive, diverse habitat and high connectivity.

  9. Nematode and arthropod genomes provide new insights into the evolution of class 2 B1 GPCRs.

    Science.gov (United States)

    Cardoso, João C R; Félix, Rute C; Power, Deborah M

    2014-01-01

    Nematodes and arthropods are the most speciose animal groups and possess Class 2 B1 G-protein coupled receptors (GPCRs). Existing models of invertebrate Class 2 B1 GPCR evolution are mainly centered on Caenorhabditis elegans and Drosophila melanogaster and a few other nematode and arthropod representatives. The present study reevaluates the evolution of metazoan Class 2 B1 GPCRs and orthologues by exploring the receptors in several nematode and arthropod genomes and comparing them to the human receptors. Three novel receptor phylogenetic clusters were identified and designated cluster A, cluster B and PDF-R-related cluster. Clusters A and B were identified in several nematode and arthropod genomes but were absent from D. melanogaster and Culicidae genomes, whereas the majority of the members of the PDF-R-related cluster were from nematodes. Cluster A receptors were nematode and arthropod-specific but shared a conserved gene environment with human receptor loci. Cluster B members were orthologous to human GCGR, PTHR and Secretin members with which they probably shared a common origin. PDF-R and PDF-R related clusters were present in representatives of both nematodes and arthropods. The results of comparative analysis of GPCR evolution and diversity in protostomes confirm previous notions that C. elegans and D. melanogaster genomes are not good representatives of nematode and arthropod phyla. We hypothesize that at least four ancestral Class 2 B1 genes emerged early in the metazoan radiation, which after the protostome-deuterostome split underwent distinct selective pressures that resulted in duplication and deletion events that originated the current Class 2 B1 GPCRs in nematode and arthropod genomes.

  10. Lipoprotein Particles in Adolescents and Young Women With PCOS Provide Insights Into Their Cardiovascular Risk.

    Science.gov (United States)

    Gourgari, E; Lodish, M; Shamburek, R; Keil, M; Wesley, R; Walter, M; Sampson, M; Bernstein, S; Khurana, D; Lyssikatos, C; Ten, S; Dobs, A; Remaley, A T; Stratakis, C A

    2015-11-01

    Adult women with polycystic ovarian syndrome (PCOS) have an increased risk for cardiovascular disease, but the evidence for this is controversial in adolescents and young women with PCOS. Measurement of low-density lipoprotein (LDL) particle number, measured by nuclear magnetic resonance spectroscopy is a novel technology to assess cardiovascular risk. The objective of the study was to evaluate lipoprotein particle number and size in young women with PCOS and its relationship with insulin resistance and hyperandrogenism. This was a cross-sectional case control study. The study was conducted at a clinical research center. Women with PCOS (n = 35) and normal controls (n = 20) participated in the study. Blood samples and anthropometric measures were obtained. LDL particle size and number were measured using nuclear magnetic resonance spectroscopy. A secondary outcome was to investigate the correlation of LDL particle number with high-sensitivity C-reactive protein, waist to hip ratio, hyperandrogenism, insulin resistance, and adiponectin. Women with PCOS had higher LDL particle number when compared with healthy controls (935 ± 412 vs 735 ± 264, P = .032); LDL particle number correlated strongly with high-sensitivity C-reactive protein (r = 0.37, P = .006) and waist-to-hip (r = 0.57, P = .0003). The higher LDL particle number was driven mainly due to differences in the small LDL particle number (sLDLp), with PCOS patients having more sLDLp (348 ± 305 vs 178 ± 195, P = .015). The sLDLp correlated with the Matsuda index (r = -0.51, P = .0001), homeostasis model assessment index of insulin resistance (r = 0.41, P = .002), and adiponectin (r = -0.46, P = .0004) but not with T. Adolescent and young women with PCOS have an atherogenic lipoprotein profile suggestive of increased cardiovascular risk that appears to be driven by the degree of visceral adiposity and insulin resistance.

  11. SSR marker variations in Brassica species provide insight into the origin and evolution of Brassica amphidiploids.

    Science.gov (United States)

    Thakur, Ajay Kumar; Singh, Kunwar Harendra; Singh, Lal; Nanjundan, Joghee; Khan, Yasin Jeshima; Singh, Dhiraj

    2018-01-01

    Oilseed Brassica represents an important group of oilseed crops with a long history of evolution and cultivation. To understand the origin and evolution of Brassica amphidiploids, simple sequence repeat (SSR) markers were used to unravel genetic variations in three diploids and three amphidiploid Brassica species of U's triangle along with Eruca sativa as an outlier. Of 124 Brassica-derived SSR loci assayed, 100% cross-transferability was obtained for B. juncea and three subspecies of B. rapa , while lowest cross-transferability (91.93%) was obtained for Eruca sativa . The average % age of cross-transferability across all the seven species was 98.15%. The number of alleles detected at each locus ranged from one to six with an average of 3.41 alleles per primer pair. Neighbor-Joining-based dendrogram divided all the 40 accessions into two main groups composed of B. juncea / B. nigra/B. rapa and B. carinata/B. napus/B. oleracea . C-genome of oilseed Brassica species remained relatively more conserved than A- and B-genome. A- genome present in B. juncea and B. napus seems distinct from each other and hence provides great opportunity for generating diversity through synthesizing amphidiploids from different sources of A- genome. B. juncea had least intra-specific distance indicating narrow genetic base. B. rapa appears to be more primitive species from which other two diploid species might have evolved. The SSR marker set developed in this study will assist in DNA fingerprinting of various Brassica species cultivars, evaluating the genetic diversity in Brassica germplasm, genome mapping and construction of linkage maps, gene tagging and various other genomics-related studies in Brassica species. Further, the evolutionary relationship established among various Brassica species would assist in formulating suitable breeding strategies for widening the genetic base of Brassica amphidiploids by exploiting the genetic diversity present in diploid progenitor gene pools.

  12. Wing shape of four new bee fossils (Hymenoptera: Anthophila provides insights to bee evolution.

    Directory of Open Access Journals (Sweden)

    Manuel Dehon

    Full Text Available Bees (Anthophila are one of the major groups of angiosperm-pollinating insects and accordingly are widely studied in both basic and applied research, for which it is essential to have a clear understanding of their phylogeny, and evolutionary history. Direct evidence of bee evolutionary history has been hindered by a dearth of available fossils needed to determine the timing and tempo of their diversification, as well as episodes of extinction. Here we describe four new compression fossils of bees from three different deposits (Miocene of la Cerdanya, Spain; Oligocene of Céreste, France; and Eocene of the Green River Formation, U.S.A.. We assess the similarity of the forewing shape of the new fossils with extant and fossil taxa using geometric morphometrics analyses. Predictive discriminant analyses show that three fossils share similar forewing shapes with the Apidae [one of uncertain tribal placement and perhaps near Euglossini, one definitive bumble bee (Bombini, and one digger bee (Anthophorini], while one fossil is more similar to the Andrenidae. The corbiculate fossils are described as Euglossopteryx biesmeijeri De Meulemeester, Michez, & Engel, gen. nov. sp. nov. (type species of Euglossopteryx Dehon & Engel, n. gen. and Bombus cerdanyensis Dehon, De Meulemeester, & Engel, sp. nov. They provide new information on the distribution and timing of particular corbiculate groups, most notably the extension into North America of possible Eocene-Oligocene cooling-induced extinctions. Protohabropoda pauli De Meulemeester & Michez, gen. nov. sp. nov. (type species of Protohabropoda Dehon & Engel, n. gen. reinforces previous hypotheses of anthophorine evolution in terms of ecological shifts by the Oligocene from tropical to mesic or xeric habitats. Lastly, a new fossil of the Andreninae, Andrena antoinei Michez & De Meulemeester, sp. nov., further documents the presence of the today widespread genus Andrena Fabricius in the Late Oligocene of France.

  13. Wing shape of four new bee fossils (Hymenoptera: Anthophila) provides insights to bee evolution.

    Science.gov (United States)

    Dehon, Manuel; Michez, Denis; Nel, André; Engel, Michael S; De Meulemeester, Thibaut

    2014-01-01

    Bees (Anthophila) are one of the major groups of angiosperm-pollinating insects and accordingly are widely studied in both basic and applied research, for which it is essential to have a clear understanding of their phylogeny, and evolutionary history. Direct evidence of bee evolutionary history has been hindered by a dearth of available fossils needed to determine the timing and tempo of their diversification, as well as episodes of extinction. Here we describe four new compression fossils of bees from three different deposits (Miocene of la Cerdanya, Spain; Oligocene of Céreste, France; and Eocene of the Green River Formation, U.S.A.). We assess the similarity of the forewing shape of the new fossils with extant and fossil taxa using geometric morphometrics analyses. Predictive discriminant analyses show that three fossils share similar forewing shapes with the Apidae [one of uncertain tribal placement and perhaps near Euglossini, one definitive bumble bee (Bombini), and one digger bee (Anthophorini)], while one fossil is more similar to the Andrenidae. The corbiculate fossils are described as Euglossopteryx biesmeijeri De Meulemeester, Michez, & Engel, gen. nov. sp. nov. (type species of Euglossopteryx Dehon & Engel, n. gen.) and Bombus cerdanyensis Dehon, De Meulemeester, & Engel, sp. nov. They provide new information on the distribution and timing of particular corbiculate groups, most notably the extension into North America of possible Eocene-Oligocene cooling-induced extinctions. Protohabropoda pauli De Meulemeester & Michez, gen. nov. sp. nov. (type species of Protohabropoda Dehon & Engel, n. gen.) reinforces previous hypotheses of anthophorine evolution in terms of ecological shifts by the Oligocene from tropical to mesic or xeric habitats. Lastly, a new fossil of the Andreninae, Andrena antoinei Michez & De Meulemeester, sp. nov., further documents the presence of the today widespread genus Andrena Fabricius in the Late Oligocene of France.

  14. Echidna venom gland transcriptome provides insights into the evolution of monotreme venom.

    Directory of Open Access Journals (Sweden)

    Emily S W Wong

    Full Text Available Monotremes (echidna and platypus are egg-laying mammals. One of their most unique characteristic is that males have venom/crural glands that are seasonally active. Male platypuses produce venom during the breeding season, delivered via spurs, to aid in competition against other males. Echidnas are not able to erect their spurs, but a milky secretion is produced by the gland during the breeding season. The function and molecular composition of echidna venom is as yet unknown. Hence, we compared the deeply sequenced transcriptome of an in-season echidna crural gland to that of a platypus and searched for putative venom genes to provide clues into the function of echidna venom and the evolutionary history of monotreme venom. We found that the echidna venom gland transcriptome was markedly different from the platypus with no correlation between the top 50 most highly expressed genes. Four peptides found in the venom of the platypus were detected in the echidna transcriptome. However, these genes were not highly expressed in echidna, suggesting that they are the remnants of the evolutionary history of the ancestral venom gland. Gene ontology terms associated with the top 100 most highly expressed genes in echidna, showed functional terms associated with steroidal and fatty acid production, suggesting that echidna "venom" may play a role in scent communication during the breeding season. The loss of the ability to erect the spur and other unknown evolutionary forces acting in the echidna lineage resulted in the gradual decay of venom components and the evolution of a new role for the crural gland.

  15. Hierarchical partitioning of metazoan protein conservation profiles provides new functional insights.

    Directory of Open Access Journals (Sweden)

    Jonathan Witztum

    Full Text Available The availability of many complete, annotated proteomes enables the systematic study of the relationships between protein conservation and functionality. We explore this question based solely on the presence or absence of protein homologues (a.k.a. conservation profiles. We study 18 metazoans, from two distinct points of view: the human's and the fly's. Using the GOrilla gene ontology (GO analysis tool, we explore functional enrichment of the "universal proteins", those with homologues in all 17 other species, and of the "non-universal proteins". A large number of GO terms are strongly enriched in both human and fly universal proteins. Most of these functions are known to be essential. A smaller number of GO terms, exhibiting markedly different properties, are enriched in both human and fly non-universal proteins. We further explore the non-universal proteins, whose conservation profiles are consistent with the "tree of life" (TOL consistent, as well as the TOL inconsistent proteins. Finally, we applied Quantum Clustering to the conservation profiles of the TOL consistent proteins. Each cluster is strongly associated with one or a small number of specific monophyletic clades in the tree of life. The proteins in many of these clusters exhibit strong functional enrichment associated with the "life style" of the related clades. Most previous approaches for studying function and conservation are "bottom up", studying protein families one by one, and separately assessing the conservation of each. By way of contrast, our approach is "top down". We globally partition the set of all proteins hierarchically, as described above, and then identify protein families enriched within different subdivisions. While supporting previous findings, our approach also provides a tool for discovering novel relations between protein conservation profiles, functionality, and evolutionary history as represented by the tree of life.

  16. Multidimensional proteomics analysis of amniotic fluid to provide insight into the mechanisms of idiopathic preterm birth.

    Directory of Open Access Journals (Sweden)

    Irina A Buhimschi

    2008-04-01

    Full Text Available Though recent advancement in proteomics has provided a novel perspective on several distinct pathogenetic mechanisms leading to preterm birth (inflammation, bleeding, the etiology of most preterm births still remains elusive. We conducted a multidimensional proteomic analysis of the amniotic fluid to identify pathways related to preterm birth in the absence of inflammation or bleeding.A proteomic fingerprint was generated from fresh amniotic fluid using surface-enhanced laser desorbtion ionization time of flight (SELDI-TOF mass spectrometry in a total of 286 consecutive samples retrieved from women who presented with signs or symptoms of preterm labor or preterm premature rupture of the membranes. Inflammation and/or bleeding proteomic patterns were detected in 32% (92/286 of the SELDI tracings. In the remaining tracings, a hierarchical algorithm was applied based on descriptors quantifying similarity/dissimilarity among proteomic fingerprints. This allowed identification of a novel profile (Q-profile based on the presence of 5 SELDI peaks in the 10-12.5 kDa mass area. Women displaying the Q-profile (mean+/-SD, gestational age: 25+/-4 weeks, n = 40 were more likely to deliver preterm despite expectant management in the context of intact membranes and normal amniotic fluid clinical results. Utilizing identification-centered proteomics techniques (fluorescence two-dimensional differential gel electrophoresis, robotic tryptic digestion and mass spectrometry coupled with Protein ANalysis THrough Evolutionary Relationships (PANTHER ontological classifications, we determined that in amniotic fluids with Q-profile the differentially expressed proteins are primarily involved in non-inflammatory biological processes such as protein metabolism, signal transduction and transport.Proteomic profiling of amniotic fluid coupled with non-hierarchical bioinformatics algorithms identified a subgroup of patients at risk for preterm birth in the absence of intra

  17. Transcriptome analysis of Crossostephium chinensis provides insight into the molecular basis of salinity stress responses.

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    Haiyan Yang

    Full Text Available Soil salinization is becoming a limitation to the utilization of ornamental plants worldwide. Crossostephium chinensis (Linnaeus Makino is often cultivated along the southeast coast of China for its desirable ornamental qualities and high salt tolerance. However, little is known about the genomic background of the salt tolerance mechanism in C. chinensis. In the present study, we used Illumina paired-end sequencing to systematically investigate leaf transcriptomes derived from C. chinensis seedlings grown under normal conditions and under salt stress. A total of 105,473,004 bp of reads were assembled into 163,046 unigenes, of which 65,839 (40.38% of the total and 54,342 (33.32% of the total were aligned in Swiss-Prot and Nr protein, respectively. A total of 11,331 (6.95% differentially expressed genes (DEGs were identified among three comparisons, including 2,239 in 'ST3 vs ST0', 5,880 in 'ST9 vs ST3' and 9,718 in 'ST9 vs ST0', and they were generally classified into 26 Gene Ontology terms and 58 Kyoto Encyclopedia of Genes and Genomes (KEGG pathway terms. Many genes encoding important transcription factors (e.g., WRKY, MYB, and AP2/EREBP and proteins involved in starch and sucrose metabolism, arginine and proline metabolism, plant hormone signal transduction, amino acid biosynthesis, plant-pathogen interactions and carbohydrate metabolism, among others, were substantially up-regulated under salt stress. These genes represent important candidates for studying the salt-response mechanism and molecular biology of C. chinensis and its relatives. Our findings provide a genomic sequence resource for functional genetic assignments in C. chinensis. These transcriptome datasets will help elucidate the molecular mechanisms responsible for salt-stress tolerance in C. chinensis and facilitate the breeding of new stress-tolerant cultivars for high-saline areas using this valuable genetic resource.

  18. Comparative transcriptomic analysis provides insights into antibacterial mechanisms of Branchiostoma belcheri under Vibrio parahaemolyticus infection.

    Science.gov (United States)

    Zhang, Qi-Lin; Zhu, Qian-Hua; Liang, Ming-Zhong; Wang, Feng; Guo, Jun; Deng, Xian-Yu; Chen, Jun-Yuan; Wang, Yu-Jun; Lin, Lian-Bing

    2018-05-01

    Amphioxus, a basal chordate, is widely considered to be an existing proxy of the invertebrate ancestor of vertebrates, and it exhibits susceptibility to various pathogen infections and pathogenic mimic challenges. Here, in order to understand more clearly its antibacterial mechanisms, we analyzed the ribosomal RNA (rRNA)-depleted transcriptome of Chinese amphioxus (Branchiostoma belcheri) infected with Vibrio parahaemolyticus (V. p.) via next-generation deep sequencing technology (RNA-seq). We identified a total of 3214 differentially expressed genes (DEGs) by comparing V. p.-infected and control transcriptome libraries, including 2219 significantly up-regulated and 995 significantly down-regulated DEGs in V. p.-infected amphioxus. The DEGs with the top 10 most dramatic expression fold changes after V. p. infection, as well as 53 immune-related DEGs (IRDs) belonging to four primary categories of innate immunity were analyzed further. Through gene ontology (GO) and pathway enrichment analysis, DEGs were found to be primarily related to immune processes, apoptosis, catabolic and metabolic processes, binding and enzyme activity, while pathways involving bacterial infection, immune signaling, immune response, cancer, and apoptosis were overrepresented. We validated the RNA-seq results by detecting the expression levels of 10 IRDs using qRT-PCR, and we surveyed the dynamic variation in gene expression for these IRDs at 0, 6, 12, 24, and 48 h after V. p. Subsequently, according to the RNA-seq results, the presence of a primitive Toll-like receptor (TLR)-mediated antibacterial immune signaling pathway was predicted in B. belcheri. This study provides valuable information regarding antibacterial immunity for further research into the evolution of immunity in vertebrates and broadens our understanding of the innate immune response against bacterial invasion in amphioxus. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Fish genomes provide novel insights into the evolution of vertebrate secretin receptors and their ligand.

    Science.gov (United States)

    Cardoso, João C R; Félix, Rute C; Trindade, Marlene; Power, Deborah M

    2014-12-01

    The secretin receptor (SCTR) is a member of Class 2 subfamily B1 GPCRs and part of the PAC1/VPAC receptor subfamily. This receptor has long been known in mammals but has only recently been identified in other vertebrates including teleosts, from which it was previously considered to be absent. The ligand for SCTR in mammals is secretin (SCT), an important gastrointestinal peptide, which in teleosts has not yet been isolated, or the gene identified. This study revises the evolutionary model previously proposed for the secretin-GPCRs in metazoan by analysing in detail the fishes, the most successful of the extant vertebrates. All the Actinopterygii genomes analysed and the Chondrichthyes and Sarcopterygii fish possess a SCTR gene that shares conserved sequence, structure and synteny with the tetrapod homologue. Phylogenetic clustering and gene environment comparisons revealed that fish and tetrapod SCTR shared a common origin and diverged early from the PAC1/VPAC subfamily group. In teleosts SCTR duplicated as a result of the fish specific whole genome duplication but in all the teleost genomes analysed, with the exception of tilapia (Oreochromis niloticus), one of the duplicates was lost. The function of SCTR in teleosts is unknown but quantitative PCR revealed that in both sea bass (Dicentrarchus labrax) and tilapia (Oreochromis mossambicus) transcript abundance is high in the gastrointestinal tract suggesting it may intervene in similar processes to those in mammals. In contrast, no gene encoding the ligand SCT was identified in the ray-finned fishes (Actinopterygii) although it was present in the coelacanth (lobe finned fish, Sarcopterygii) and in the elephant shark (holocephalian). The genes in linkage with SCT in tetrapods and coelacanth were also identified in ray-finned fishes supporting the idea that it was lost from their genome. At present SCTR remains an orphan receptor in ray-finned fishes and it will be of interest in the future to establish why SCT was

  20. Andrographis paniculata transcriptome provides molecular insights into tissue-specific accumulation of medicinal diterpenes.

    Science.gov (United States)

    Garg, Anchal; Agrawal, Lalit; Misra, Rajesh Chandra; Sharma, Shubha; Ghosh, Sumit

    2015-09-02

    Kalmegh (Andrographis paniculata) has been widely exploited in traditional medicine for the treatment of infectious diseases and health disorders. Ent-labdane-related diterpene (ent-LRD) specialized (i.e., secondary) metabolites of kalmegh such as andrographolide, neoandrographolide and 14-deoxy-11,12-didehydroandrographolide, are known for variety of pharmacological activities. However, due to the lack of genomic and transcriptomic information, underlying molecular basis of ent-LRDs biosynthesis has remained largely unknown. To identify candidate genes of the ent-LRD biosynthetic pathway, we performed comparative transcriptome analysis using leaf and root tissues that differentially accumulate ent-LRDs. De novo assembly of Illumina HiSeq2000 platform-generated paired-end sequencing reads resulted into 69,011 leaf and 64,244 root transcripts which were assembled into a total of 84,628 unique transcripts. Annotation of these transcripts to the Uniprot, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Carbohydrate-Active Enzymes (CAZy) databases identified candidate transcripts of the ent-LRD biosynthetic pathway. These included transcripts that encode enzymes of the plastidial 2C-methyl-D-erythritol-4-phosphate pathway which provides C5 isoprenoid precursors for the ent-LRDs biosynthesis, geranylgeranyl diphosphate synthase, class II diterpene synthase (diTPS), cytochrome P450 monooxygenase and glycosyltransferase. Three class II diTPSs (ApCPS1, ApCPS2 and ApCPS3) that showed distinct tissue-specific expression profiles and are phylogenetically related to the dicotyledon ent-copalyl diphosphate synthases, are identified. ApCPS1, ApCPS2 and ApCPS3 encode for 832-, 817- and 797- amino acids proteins of 55-63 % identity, respectively. Spatio-temporal patterns of transcripts and ent-LRDs accumulation are consistent with the involvement of ApCPS1 in general (i.e., primary) metabolism for the biosynthesis of phytohormone gibberellin, ApCPS2 in leaf specialized ent

  1. The Epigenome of Schistosoma mansoni Provides Insight about How Cercariae Poise Transcription until Infection

    Science.gov (United States)

    Freitag, Michael; Parrinello, Hugues; Groth, Marco; Emans, Rémi; Cosseau, Céline; Grunau, Christoph

    2015-01-01

    Background Chromatin structure can control gene expression and can define specific transcription states. For example, bivalent methylation of histone H3K4 and H3K27 is linked to poised transcription in vertebrate embryonic stem cells (ESC). It allows them to rapidly engage specific developmental pathways. We reasoned that non-vertebrate metazoans that encounter a similar developmental constraint (i.e. to quickly start development into a new phenotype) might use a similar system. Schistosomes are parasitic platyhelminthes that are characterized by passage through two hosts: a mollusk as intermediate host and humans or rodents as definitive host. During its development, the parasite undergoes drastic changes, most notable immediately after infection of the definitive host, i.e. during the transition from the free-swimming cercariae into adult worms. Methodology/Principal Findings We used Chromatin Immunoprecipitation followed by massive parallel sequencing (ChIP-Seq) to analyze genome-wide chromatin structure of S. mansoni on the level of histone modifications (H3K4me3, H3K27me3, H3K9me3, and H3K9ac) in cercariae, schistosomula and adults (available at http://genome.univ-perp.fr). We saw striking differences in chromatin structure between the developmental stages, but most importantly we found that cercariae possess a specific combination of marks at the transcription start sites (TSS) that has similarities to a structure found in ESC. We demonstrate that in cercariae no transcription occurs, and we provide evidences that cercariae do not possess large numbers of canonical stem cells. Conclusions/Significance We describe here a broad view on the epigenome of a metazoan parasite. Most notably, we find bivalent histone H3 methylation in cercariae. Methylation of H3K27 is removed during transformation into schistosomula (and stays absent in adults) and transcription is activated. In addition, shifts of H3K9 methylation and acetylation occur towards upstream and

  2. The Epigenome of Schistosoma mansoni Provides Insight about How Cercariae Poise Transcription until Infection.

    Directory of Open Access Journals (Sweden)

    David Roquis

    Full Text Available Chromatin structure can control gene expression and can define specific transcription states. For example, bivalent methylation of histone H3K4 and H3K27 is linked to poised transcription in vertebrate embryonic stem cells (ESC. It allows them to rapidly engage specific developmental pathways. We reasoned that non-vertebrate metazoans that encounter a similar developmental constraint (i.e. to quickly start development into a new phenotype might use a similar system. Schistosomes are parasitic platyhelminthes that are characterized by passage through two hosts: a mollusk as intermediate host and humans or rodents as definitive host. During its development, the parasite undergoes drastic changes, most notable immediately after infection of the definitive host, i.e. during the transition from the free-swimming cercariae into adult worms.We used Chromatin Immunoprecipitation followed by massive parallel sequencing (ChIP-Seq to analyze genome-wide chromatin structure of S. mansoni on the level of histone modifications (H3K4me3, H3K27me3, H3K9me3, and H3K9ac in cercariae, schistosomula and adults (available at http://genome.univ-perp.fr. We saw striking differences in chromatin structure between the developmental stages, but most importantly we found that cercariae possess a specific combination of marks at the transcription start sites (TSS that has similarities to a structure found in ESC. We demonstrate that in cercariae no transcription occurs, and we provide evidences that cercariae do not possess large numbers of canonical stem cells.We describe here a broad view on the epigenome of a metazoan parasite. Most notably, we find bivalent histone H3 methylation in cercariae. Methylation of H3K27 is removed during transformation into schistosomula (and stays absent in adults and transcription is activated. In addition, shifts of H3K9 methylation and acetylation occur towards upstream and downstream of the transcriptional start site (TSS. We conclude

  3. In situ tagging technique for fishes provides insight into growth and movement of invasive lionfish.

    Science.gov (United States)

    Akins, John L; Morris, James A; Green, Stephanie J

    2014-10-01

    's mass. Our study offers a novel in situ tagging technique that can be used to provide critical information on fish site fidelity, movement patterns, and growth in cases where ex situ tagging is not feasible.

  4. Insights into iron sources and pathways in the Amazon River provided by isotopic and spectroscopic studies

    Science.gov (United States)

    Mulholland, Daniel Santos; Poitrasson, Franck; Boaventura, Geraldo Resende; Allard, Thierry; Vieira, Lucieth Cruz; Santos, Roberto Ventura; Mancini, Luiz; Seyler, Patrick

    2015-02-01

    ões River have δ57Fe consistent with strong mechanical erosion in the Andean Cordillera and upland soils, as evidenced by high concentrations of Fe3+-oxides sensu lato measured by EPR. The massive dissolved and colloidal Fe removal is associated with the evolution of the physical and chemical composition of the waters (i.e., ionic strength) during mixing, which influences organo-Fe3+ and Fe3+-oxyhydroxides stability. Several models are discussed to explain Fe non-conservative behavior, including dissociation of organo-Fe complexes and the subsequent formation of solid Fe3+-oxyhydroxides and semiquinone free radicals, as evidenced by EPR spectra demonstrating that organo-Fe signals decrease as Fe3+-oxyhydroxides and free radicals signals increase. As in estuarine regions, the mechanisms involving Fe transfer and loss in the mixing zone has a negligible effect on the bulk water Fe isotopic composition. This result suggests that a tropical basin similar to the Amazon River Basin delivers to the ocean waters with an Fe isotopic composition similar to that of the Earth's continental crust.

  5. Insights to Meteorites and Impact Processes provided by Advanced EBSD Analysis

    Science.gov (United States)

    Palasse, Laurie; Berlin, Jana; Goran, Daniel; Tagle, Roald; Hamers, Maartje; Assis Fernandes, Vera; Deutsch, Alexander; Schulte, Peter; Salge, Tobias

    2013-04-01

    . For Chicxulub, the brecciated impact melt rock from borehole Yaxcopoil-1 (Unit 5, 861.72 m) [3] reveals that the ballen microstructure is only semi-amorphous and cross cuts a fine grained recrystallised microstructure. (C) CB chondrite Gujba: EDS and EBSD data were acquired simultaneously to study chemical and physical interactions between preexisting metal particles and the invading silicate-rich impact melt matrix. Metal particles appear to have different thermal histories. Some of them consist of many small grains (average diameter ~10 µm), which have a similar orientation when they are surrounded by arcuate Fe,Cr-sulfides. [4]. Acknowledgements: P. Claeys, R.H. Jones, ICDP and the Museum of Natural History Berlin for providing samples. References: [1] T. Salge (2007) PhD thesis, Humboldt Universität zu Berlin, 130p. [2] A. P. Jones et al. (2000) Lect. Notes in Earth Sciences 91: 343-361. [3] M. J. Nelson et al. (2012) GCA 86: 1-20. [4]. J. Berlin et al. (2013) 44th LPSC # 2439

  6. Comprehensive Care For Joint Replacement Model - Provider Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — Comprehensive Care for Joint Replacement Model - provider data. This data set includes provider data for two quality measures tracked during an episode of care:...

  7. Using Models to Inform Policy: Insights from Modeling the Complexities of Global Polio Eradication

    Science.gov (United States)

    Thompson, Kimberly M.

    Drawing on over 20 years of experience modeling risks in complex systems, this talk will challenge SBP participants to develop models that provide timely and useful answers to critical policy questions when decision makers need them. The talk will include reflections on the opportunities and challenges associated with developing integrated models for complex problems and communicating their results effectively. Dr. Thompson will focus the talk largely on collaborative modeling related to global polio eradication and the application of system dynamics tools. After successful global eradication of wild polioviruses, live polioviruses will still present risks that could potentially lead to paralytic polio cases. This talk will present the insights of efforts to use integrated dynamic, probabilistic risk, decision, and economic models to address critical policy questions related to managing global polio risks. Using a dynamic disease transmission model combined with probabilistic model inputs that characterize uncertainty for a stratified world to account for variability, we find that global health leaders will face some difficult choices, but that they can take actions that will manage the risks effectively. The talk will emphasize the need for true collaboration between modelers and subject matter experts, and the importance of working with decision makers as partners to ensure the development of useful models that actually get used.

  8. Physically-insightful equivalent circuit models for electromagnetic periodic structures

    Science.gov (United States)

    Mesa, F.; Rodríguez-Berral, R.; Medina, F.

    2018-02-01

    In this presentation it will be discussed how to obtain analytical or quasi-analytical equivalent circuits to deal with periodic structures such as frequency selective surfaces and/or metasurfaces. Both the topology and the values of the involved elements of these circuits are obtained from a basic rationale to solve the corresponding integral equation. This procedure, besides providing a very efficient analysis/design tool, allows for a good physical insight into the operating mechanisms of the structure in contrast with the almost blind numerical scheme of commercial simulators.

  9. Structural equation modelling of determinants of customer satisfaction of mobile network providers: Case of Kolkata, India

    Directory of Open Access Journals (Sweden)

    Shibashish Chakraborty

    2014-12-01

    Full Text Available The Indian market of mobile network providers is growing rapidly. India is the second largest market of mobile network providers in the world and there is intense competition among existing players. In such a competitive market, customer satisfaction becomes a key issue. The objective of this paper is to develop a customer satisfaction model of mobile network providers in Kolkata. The results indicate that generic requirements (an aggregation of output quality and perceived value, flexibility, and price are the determinants of customer satisfaction. This study offers insights for mobile network providers to understand the determinants of customer satisfaction.

  10. Customer-Provider Strategic Alignment: A Maturity Model

    Science.gov (United States)

    Luftman, Jerry; Brown, Carol V.; Balaji, S.

    This chapter presents a new model for assessing the maturity of a ­customer-provider relationship from a collaborative service delivery perspective: the Customer-Provider Strategic Alignment Maturity (CPSAM) Model. This model builds on recent research for effectively managing the customer-provider relationship in IT service outsourcing contexts and a validated model for assessing alignment across internal IT service units and their business customers within the same organization. After reviewing relevant literature by service science and information systems researchers, the six overarching components of the maturity model are presented: value measurements, governance, partnership, communications, human resources and skills, and scope and architecture. A key assumption of the model is that all of the components need be addressed to assess and improve customer-provider alignment. Examples of specific metrics for measuring the maturity level of each component over the five levels of maturity are also presented.

  11. Insights Into Care Providers' Understandings of Life Story Work With Persons With Dementia: Findings From a Qualitative Study.

    Science.gov (United States)

    Berendonk, Charlotte; Caine, Vera

    2017-08-01

    In Germany, life story work, an approach which acknowledges humans as narrative beings and honors biographies, is required by health authorities to be integrated in care provided in nursing homes. Insufficient attention to life story work could place residents at risk of dehumanization, particularly residents with dementia, who depend on support of others to tell and make meaning of their life experiences. We conducted a qualitative study to gain insights into care providers' perceptions and practices of life story work with persons with dementia. Thirty-six care providers in 7 nursing homes participated in semistructured interviews or group discussions. We derived subjective theories (individual understandings) of care providers and higher-order concept patterns following the principles and processes of grounded theory. We found a great variation in participants' understandings of life story work. Some participants were unsure if and how life story work impacts persons with dementia. Starting points for improving the integration of life story work into practice are discussed. We conclude that care providers need a better understanding of life story work as a nursing intervention. The importance of the notion of humans as narrative beings and the multiple ways in which we story our lives as well as embody life stories needs to be further developed. Knowledge is required about the practical and systemic challenges of integrating life story work in the care of persons with dementia.

  12. Insights on PRA Review Practices: Necessity for Model Shaking

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Inn Seock; Jang, Mi suk; Kim, Seoung Rae [NESS, Daejeon (Korea, Republic of)

    2016-05-15

    Probabilistic risk assessment (PRA) is increasingly used as a technique to help ensure design and operational safety of nuclear power plants (NPPs) in the nuclear industry. Hence, there is considerable interest in the PRA quality, and as a result, a peer review of the PRA model is typically performed to ensure its technical adequacy as part of the PRA development process or for any other reason (e.g., regulatory requirement). For the PRA model to be used as a valuable vehicle for risk-informed applications, it is essential that the PRA model must yield correct and physically meaningful accident sequences and minimal cutsets for specific plant configurations or conditions relating to the applications. Hence, the existing peer review guidelines need to be updated to reflect these insights so that risk-informed applications could be more actively pursued with confidence.

  13. A proteomic approach provides new insights into the control of soil-borne plant pathogens by Bacillus species.

    Directory of Open Access Journals (Sweden)

    Omür Baysal

    Full Text Available Beneficial microorganisms (also known as biopesticides are considered to be one of the most promising methods for more rational and safe crop management practices. We used Bacillus strains EU07, QST713 and FZB24, and investigated their inhibitory effect on Fusarium. Bacterial cell cultures, cell-free supernatants and volatiles displayed varying degrees of suppressive effect. Proteomic analysis of secreted proteins from EU07 and FZB24 revealed the presence of lytic enzymes, cellulases, proteases, 1,4-β-glucanase and hydrolases, all of which contribute to degradation of the pathogen cell wall. Further proteomic investigations showed that proteins involved in metabolism, protein folding, protein degradation, translation, recognition and signal transduction cascade play an important role in the control of Fusarium oxysporum. Our findings provide new knowledge on the mechanism of action of Bacillus species and insight into biocontrol mechanisms.

  14. Modeling Market Shares of Competing (e)Care Providers

    Science.gov (United States)

    van Ooteghem, Jan; Tesch, Tom; Verbrugge, Sofie; Ackaert, Ann; Colle, Didier; Pickavet, Mario; Demeester, Piet

    In order to address the increasing costs of providing care to the growing group of elderly, efficiency gains through eCare solutions seem an obvious solution. Unfortunately not many techno-economic business models to evaluate the return of these investments are available. The construction of a business case for care for the elderly as they move through different levels of dependency and the effect of introducing an eCare service, is the intended application of the model. The simulation model presented in this paper allows for modeling evolution of market shares of competing care providers. Four tiers are defined, based on the dependency level of the elderly, for which the market shares are determined. The model takes into account available capacity of the different care providers, in- and outflow distribution between tiers and churn between providers within tiers.

  15. Characterization of hairless (Hr) and FGF5 genes provides insights into the molecular basis of hair loss in cetaceans.

    Science.gov (United States)

    Chen, Zhuo; Wang, Zhengfei; Xu, Shixia; Zhou, Kaiya; Yang, Guang

    2013-02-09

    Hair is one of the main distinguishing characteristics of mammals and it has many important biological functions. Cetaceans originated from terrestrial mammals and they have evolved a series of adaptations to aquatic environments, which are of evolutionary significance. However, the molecular mechanisms underlying their aquatic adaptations have not been well explored. This study provided insights into the evolution of hair loss during the transition from land to water by investigating and comparing two essential regulators of hair follicle development and hair follicle cycling, i.e., the Hairless (Hr) and FGF5 genes, in representative cetaceans and their terrestrial relatives. The full open reading frame sequences of the Hr and FGF5 genes were characterized in seven cetaceans. The sequence characteristics and evolutionary analyses suggested the functional loss of the Hr gene in cetaceans, which supports the loss of hair during their full adaptation to aquatic habitats. By contrast, positive selection for the FGF5 gene was found in cetaceans where a series of positively selected amino acid residues were identified. This is the first study to investigate the molecular basis of the hair loss in cetaceans. Our investigation of Hr and FGF5, two indispensable regulators of the hair cycle, provide some new insights into the molecular basis of hair loss in cetaceans. The results suggest that positive selection for the FGF5 gene might have promoted the termination of hair growth and early entry into the catagen stage of hair follicle cycling. Consequently, the hair follicle cycle was disrupted and the hair was lost completely due to the loss of the Hr gene function in cetaceans. This suggests that cetaceans have evolved an effective and complex mechanism for hair loss.

  16. A Comparative Genomic Survey Provides Novel Insights into Molecular Evolution of l-Aromatic Amino Acid Decarboxylase in Vertebrates

    Directory of Open Access Journals (Sweden)

    Yanping Li

    2018-04-01

    Full Text Available Melatonin is a pleiotropic molecule with various important physiological roles in vertebrates. l-aromatic amino acid decarboxylase (AAAD is the second enzyme for melatonin synthesis. By far, a clear-cut gene function of AAAD in the biosynthesis of melatonin has been unclear in vertebrates. Here, we provide novel insights into the evolution of AAAD based on 77 vertebrate genomes. According to our genome-wide alignments, we extracted a total of 151 aaad nucleotide sequences. A phylogenetic tree was constructed on the basis of these sequences and corresponding protein alignments, indicating that tetrapods and diploid bony fish genomes contained one aaad gene and a new aaad-like gene, which formed a novel AAAD family. However, in tetraploid teleosts, there were two copies of the aaad gene due to whole genome duplication. A subsequent synteny analysis investigated 81 aaad sequences and revealed their collinearity and systematic evolution. Interestingly, we discovered that platypus (Ornithorhynchus anatinus, Atlantic cod (Guadus morhua, Mexican tetra (Astyanax mexicanus, and a Sinocyclocheilus cavefish (S. anshuiensis have long evolutionary branches in the phylogenetic topology. We also performed pseudogene identification and selection pressure analysis; however, the results revealed a deletion of 37 amino acids in Atlantic cod and premature stop codons in the cave-restricted S. anshuiensis and A. mexicanus, suggesting weakening or disappearing rhythms in these cavefishes. Selective pressure analysis of aaad between platypus and other tetrapods showed that rates of nonsynonymous (Ka and synonymous (Ks substitutions were higher when comparing the platypus to other representative tetrapods, indicating that, in this semiaquatic mammal, the aaad gene experienced selection during the process of evolution. In summary, our current work provides novel insights into aaad genes in vertebrates from a genome-wide view.

  17. Modeling patients' acceptance of provider-delivered e-health.

    Science.gov (United States)

    Wilson, E Vance; Lankton, Nancy K

    2004-01-01

    Health care providers are beginning to deliver a range of Internet-based services to patients; however, it is not clear which of these e-health services patients need or desire. The authors propose that patients' acceptance of provider-delivered e-health can be modeled in advance of application development by measuring the effects of several key antecedents to e-health use and applying models of acceptance developed in the information technology (IT) field. This study tested three theoretical models of IT acceptance among patients who had recently registered for access to provider-delivered e-health. An online questionnaire administered items measuring perceptual constructs from the IT acceptance models (intrinsic motivation, perceived ease of use, perceived usefulness/extrinsic motivation, and behavioral intention to use e-health) and five hypothesized antecedents (satisfaction with medical care, health care knowledge, Internet dependence, information-seeking preference, and health care need). Responses were collected and stored in a central database. All tested IT acceptance models performed well in predicting patients' behavioral intention to use e-health. Antecedent factors of satisfaction with provider, information-seeking preference, and Internet dependence uniquely predicted constructs in the models. Information technology acceptance models provide a means to understand which aspects of e-health are valued by patients and how this may affect future use. In addition, antecedents to the models can be used to predict e-health acceptance in advance of system development.

  18. Silver vanadium diphosphate Ag2VP2O8: Electrochemistry and characterization of reduced material providing mechanistic insights

    International Nuclear Information System (INIS)

    Takeuchi, Esther S.; Lee, Chia-Ying; Cheng, Po-Jen; Menard, Melissa C.; Marschilok, Amy C.; Takeuchi, Kenneth J.

    2013-01-01

    Silver vanadium phosphorous oxides (Ag w V x P y O z ) are notable battery cathode materials due to their high energy density and demonstrated ability to form in-situ Ag metal nanostructured electrically conductive networks within the cathode. While analogous silver vanadium diphosphate materials have been prepared, electrochemical evaluations of these diphosphate based materials have been limited. We report here the first electrochemical study of a silver vanadium diphosphate, Ag 2 VP 2 O 8 , where the structural differences associated with phosphorous oxides versus diphosphates profoundly affect the associated electrochemistry. Reminiscent of Ag 2 VO 2 PO 4 reduction, in-situ formation of silver metal nanoparticles was observed with reduction of Ag 2 VP 2 O 8 . However, counter to Ag 2 VO 2 PO 4 reduction, Ag 2 VP 2 O 8 demonstrates a significant decrease in conductivity upon continued electrochemical reduction. Structural analysis contrasting the crystallography of the parent Ag 2 VP 2 O 8 with that of the proposed Li 2 VP 2 O 8 reduction product is employed to gain insight into the observed electrochemical reduction behavior, where the structural rigidity associated with the diphosphate anion may be associated with the observed particle fracturing upon deep electrochemical reduction. Further, the diphosphate anion structure may be associated with the high thermal stability of the partially reduced Ag 2 VP 2 O 8 materials, which bodes well for enhanced safety of batteries incorporating this material. - Graphical abstract: Structure and galvanostatic intermittent titration-type test data for silver vanadium diphosphate, Ag 2 VP 2 O 8 . Highlights: ► First electrochemical study of a silver vanadium diphosphate, Ag 2 VP 2 O 8 . ► In-situ formation of Ag 0 nanoparticles was observed upon electrochemical reduction. ► Structural analysis used to provide insight of the electrochemical behavior

  19. Physical mapping and BAC-end sequence analysis provide initial insights into the flax (Linum usitatissimum L. genome

    Directory of Open Access Journals (Sweden)

    Cloutier Sylvie

    2011-05-01

    Full Text Available Abstract Background Flax (Linum usitatissimum L. is an important source of oil rich in omega-3 fatty acids, which have proven health benefits and utility as an industrial raw material. Flax seeds also contain lignans which are associated with reducing the risk of certain types of cancer. Its bast fibres have broad industrial applications. However, genomic tools needed for molecular breeding were non existent. Hence a project, Total Utilization Flax GENomics (TUFGEN was initiated. We report here the first genome-wide physical map of flax and the generation and analysis of BAC-end sequences (BES from 43,776 clones, providing initial insights into the genome. Results The physical map consists of 416 contigs spanning ~368 Mb, assembled from 32,025 fingerprints, representing roughly 54.5% to 99.4% of the estimated haploid genome (370-675 Mb. The N50 size of the contigs was estimated to be ~1,494 kb. The longest contig was ~5,562 kb comprising 437 clones. There were 96 contigs containing more than 100 clones. Approximately 54.6 Mb representing 8-14.8% of the genome was obtained from 80,337 BES. Annotation revealed that a large part of the genome consists of ribosomal DNA (~13.8%, followed by known transposable elements at 6.1%. Furthermore, ~7.4% of sequence was identified to harbour novel repeat elements. Homology searches against flax-ESTs and NCBI-ESTs suggested that ~5.6% of the transcriptome is unique to flax. A total of 4064 putative genomic SSRs were identified and are being developed as novel markers for their use in molecular breeding. Conclusion The first genome-wide physical map of flax constructed with BAC clones provides a framework for accessing target loci with economic importance for marker development and positional cloning. Analysis of the BES has provided insights into the uniqueness of the flax genome. Compared to other plant genomes, the proportion of rDNA was found to be very high whereas the proportion of known transposable

  20. Physical mapping and BAC-end sequence analysis provide initial insights into the flax (Linum usitatissimum L.) genome.

    Science.gov (United States)

    Ragupathy, Raja; Rathinavelu, Rajkumar; Cloutier, Sylvie

    2011-05-09

    Flax (Linum usitatissimum L.) is an important source of oil rich in omega-3 fatty acids, which have proven health benefits and utility as an industrial raw material. Flax seeds also contain lignans which are associated with reducing the risk of certain types of cancer. Its bast fibres have broad industrial applications. However, genomic tools needed for molecular breeding were non existent. Hence a project, Total Utilization Flax GENomics (TUFGEN) was initiated. We report here the first genome-wide physical map of flax and the generation and analysis of BAC-end sequences (BES) from 43,776 clones, providing initial insights into the genome. The physical map consists of 416 contigs spanning ~368 Mb, assembled from 32,025 fingerprints, representing roughly 54.5% to 99.4% of the estimated haploid genome (370-675 Mb). The N50 size of the contigs was estimated to be ~1,494 kb. The longest contig was ~5,562 kb comprising 437 clones. There were 96 contigs containing more than 100 clones. Approximately 54.6 Mb representing 8-14.8% of the genome was obtained from 80,337 BES. Annotation revealed that a large part of the genome consists of ribosomal DNA (~13.8%), followed by known transposable elements at 6.1%. Furthermore, ~7.4% of sequence was identified to harbour novel repeat elements. Homology searches against flax-ESTs and NCBI-ESTs suggested that ~5.6% of the transcriptome is unique to flax. A total of 4064 putative genomic SSRs were identified and are being developed as novel markers for their use in molecular breeding. The first genome-wide physical map of flax constructed with BAC clones provides a framework for accessing target loci with economic importance for marker development and positional cloning. Analysis of the BES has provided insights into the uniqueness of the flax genome. Compared to other plant genomes, the proportion of rDNA was found to be very high whereas the proportion of known transposable elements was low. The SSRs identified from BES will be

  1. The biological and structural characterization of Mycobacterium tuberculosis UvrA provides novel insights into its mechanism of action.

    Science.gov (United States)

    Rossi, Franca; Khanduja, Jasbeer Singh; Bortoluzzi, Alessio; Houghton, Joanna; Sander, Peter; Güthlein, Carolin; Davis, Elaine O; Springer, Burkhard; Böttger, Erik C; Relini, Annalisa; Penco, Amanda; Muniyappa, K; Rizzi, Menico

    2011-09-01

    Mycobacterium tuberculosis is an extremely well adapted intracellular human pathogen that is exposed to multiple DNA damaging chemical assaults originating from the host defence mechanisms. As a consequence, this bacterium is thought to possess highly efficient DNA repair machineries, the nucleotide excision repair (NER) system amongst these. Although NER is of central importance to DNA repair in M. tuberculosis, our understanding of the processes in this species is limited. The conserved UvrABC endonuclease represents the multi-enzymatic core in bacterial NER, where the UvrA ATPase provides the DNA lesion-sensing function. The herein reported genetic analysis demonstrates that M. tuberculosis UvrA is important for the repair of nitrosative and oxidative DNA damage. Moreover, our biochemical and structural characterization of recombinant M. tuberculosis UvrA contributes new insights into its mechanism of action. In particular, the structural investigation reveals an unprecedented conformation of the UvrB-binding domain that we propose to be of functional relevance. Taken together, our data suggest UvrA as a potential target for the development of novel anti-tubercular agents and provide a biochemical framework for the identification of small-molecule inhibitors interfering with the NER activity in M. tuberculosis.

  2. NEW INSIGHT INTO THE SOLAR SYSTEM’S TRANSITION DISK PHASE PROVIDED BY THE METAL-RICH CARBONACEOUS CHONDRITE ISHEYEVO

    International Nuclear Information System (INIS)

    Morris, Melissa A.; Garvie, Laurence A. J.; Knauth, L. Paul

    2015-01-01

    Many aspects of planet formation are controlled by the amount of gas remaining in the natal protoplanetary disks (PPDs). Infrared observations show that PPDs undergo a transition stage at several megayears, during which gas densities are reduced. Our Solar System would have experienced such a stage. However, there is currently no data that provides insight into this crucial time in our PPD’s evolution. We show that the Isheyevo meteorite contains the first definitive evidence for a transition disk stage in our Solar System. Isheyevo belongs to a class of metal-rich meteorites whose components have been dated at almost 5 Myr after formation of Ca, Al-rich inclusions, and exhibits unique sedimentary layers that imply formation through gentle sedimentation. We show that such layering can occur via the gentle sweep-up of material found in the impact plume resulting from the collision of two planetesimals. Such sweep-up requires gas densities consistent with observed transition disks (10 −12 –10 −11 g cm −3 ). As such, Isheyevo presents the first evidence of our own transition disk and provides new constraints on the evolution of our solar nebula

  3. NEW INSIGHT INTO THE SOLAR SYSTEM’S TRANSITION DISK PHASE PROVIDED BY THE METAL-RICH CARBONACEOUS CHONDRITE ISHEYEVO

    Energy Technology Data Exchange (ETDEWEB)

    Morris, Melissa A. [State University of New York, Cortland, NY 13045 (United States); Garvie, Laurence A. J. [Center for Meteorite Studies, Arizona State University, Tempe, AZ 85287 (United States); Knauth, L. Paul, E-mail: melissa.morris@cortland.edu [School of Earth and Space Exploration, Arizona State University, Tempe, AZ 85287 (United States)

    2015-03-10

    Many aspects of planet formation are controlled by the amount of gas remaining in the natal protoplanetary disks (PPDs). Infrared observations show that PPDs undergo a transition stage at several megayears, during which gas densities are reduced. Our Solar System would have experienced such a stage. However, there is currently no data that provides insight into this crucial time in our PPD’s evolution. We show that the Isheyevo meteorite contains the first definitive evidence for a transition disk stage in our Solar System. Isheyevo belongs to a class of metal-rich meteorites whose components have been dated at almost 5 Myr after formation of Ca, Al-rich inclusions, and exhibits unique sedimentary layers that imply formation through gentle sedimentation. We show that such layering can occur via the gentle sweep-up of material found in the impact plume resulting from the collision of two planetesimals. Such sweep-up requires gas densities consistent with observed transition disks (10{sup −12}–10{sup −11} g cm{sup −3}). As such, Isheyevo presents the first evidence of our own transition disk and provides new constraints on the evolution of our solar nebula.

  4. The Jujube Genome Provides Insights into Genome Evolution and the Domestication of Sweetness/Acidity Taste in Fruit Trees.

    Directory of Open Access Journals (Sweden)

    Jian Huang

    2016-12-01

    Full Text Available Jujube (Ziziphus jujuba Mill. belongs to the Rhamnaceae family and is a popular fruit tree species with immense economic and nutritional value. Here, we report a draft genome of the dry jujube cultivar 'Junzao' and the genome resequencing of 31 geographically diverse accessions of cultivated and wild jujubes (Ziziphus jujuba var. spinosa. Comparative analysis revealed that the genome of 'Dongzao', a fresh jujube, was ~86.5 Mb larger than that of the 'Junzao', partially due to the recent insertions of transposable elements in the 'Dongzao' genome. We constructed eight proto-chromosomes of the common ancestor of Rhamnaceae and Rosaceae, two sister families in the order Rosales, and elucidated the evolutionary processes that have shaped the genome structures of modern jujubes. Population structure analysis revealed the complex genetic background of jujubes resulting from extensive hybridizations between jujube and its wild relatives. Notably, several key genes that control fruit organic acid metabolism and sugar content were identified in the selective sweep regions. We also identified S-locus genes controlling gametophytic self-incompatibility and investigated haplotype patterns of the S locus in the jujube genomes, which would provide a guideline for parent selection for jujube crossbreeding. This study provides valuable genomic resources for jujube improvement, and offers insights into jujube genome evolution and its population structure and domestication.

  5. The Jujube Genome Provides Insights into Genome Evolution and the Domestication of Sweetness/Acidity Taste in Fruit Trees.

    Science.gov (United States)

    Huang, Jian; Zhang, Chunmei; Zhao, Xing; Fei, Zhangjun; Wan, KangKang; Zhang, Zhong; Pang, Xiaoming; Yin, Xiao; Bai, Yang; Sun, Xiaoqing; Gao, Lizhi; Li, Ruiqiang; Zhang, Jinbo; Li, Xingang

    2016-12-01

    Jujube (Ziziphus jujuba Mill.) belongs to the Rhamnaceae family and is a popular fruit tree species with immense economic and nutritional value. Here, we report a draft genome of the dry jujube cultivar 'Junzao' and the genome resequencing of 31 geographically diverse accessions of cultivated and wild jujubes (Ziziphus jujuba var. spinosa). Comparative analysis revealed that the genome of 'Dongzao', a fresh jujube, was ~86.5 Mb larger than that of the 'Junzao', partially due to the recent insertions of transposable elements in the 'Dongzao' genome. We constructed eight proto-chromosomes of the common ancestor of Rhamnaceae and Rosaceae, two sister families in the order Rosales, and elucidated the evolutionary processes that have shaped the genome structures of modern jujubes. Population structure analysis revealed the complex genetic background of jujubes resulting from extensive hybridizations between jujube and its wild relatives. Notably, several key genes that control fruit organic acid metabolism and sugar content were identified in the selective sweep regions. We also identified S-locus genes controlling gametophytic self-incompatibility and investigated haplotype patterns of the S locus in the jujube genomes, which would provide a guideline for parent selection for jujube crossbreeding. This study provides valuable genomic resources for jujube improvement, and offers insights into jujube genome evolution and its population structure and domestication.

  6. Taxonomic and functional diversity provides insight into microbial pathways and stress responses in the saline Qinghai Lake, China.

    Directory of Open Access Journals (Sweden)

    Qiuyuan Huang

    Full Text Available Microbe-mediated biogeochemical cycles contribute to the global climate system and have sensitive responses and feedbacks to environmental stress caused by climate change. Yet, little is known about the effects of microbial biodiversity (i.e., taxonmic and functional diversity on biogeochemical cycles in ecosytems that are highly sensitive to climate change. One such sensitive ecosystem is Qinghai Lake, a high-elevation (3196 m saline (1.4% lake located on the Tibetan Plateau, China. This study provides baseline information on the microbial taxonomic and functional diversity as well as the associated stress response genes. Illumina metagenomic and metatranscriptomic datasets were generated from lake water samples collected at two sites (B and E. Autotrophic Cyanobacteria dominated the DNA samples, while heterotrophic Proteobacteria dominated the RNA samples at both sites. Photoheterotrophic Loktanella was also present at both sites. Photosystem II was the most active pathway at site B; while, oxidative phosphorylation was most active at site E. Organisms that expressed photosystem II or oxidative phosphorylation also expressed genes involved in photoprotection and oxidative stress, respectively. Assimilatory pathways associated with the nitrogen cycle were dominant at both sites. Results also indicate a positive relationship between functional diversity and the number of stress response genes. This study provides insight into the stress resilience of microbial metabolic pathways supported by greater taxonomic diversity, which may affect the microbial community response to climate change.

  7. Mechanisms of cell death in canine parvovirus-infected cells provide intuitive insights to developing nanotools for medicine

    Directory of Open Access Journals (Sweden)

    Jonna Nykky

    2010-06-01

    Full Text Available Jonna Nykky, Jenni E Tuusa, Sanna Kirjavainen, Matti Vuento, Leona GilbertNanoscience Center and Department of Biological and Environmental Science, University of Jyväskylä, FinlandAbstract: Viruses have great potential as nanotools in medicine for gene transfer, targeted gene delivery, and oncolytic cancer virotherapy. Here we have studied cell death mechanisms of canine parvovirus (CPV to increase the knowledge on the CPV life cycle in order to facilitate the development of better parvovirus vectors. Morphological studies of CPV-infected Norden laboratory feline kidney (NLFK cells and canine fibroma cells (A72 displayed characteristic apoptotic events. Apoptosis was further confirmed by activation of caspases and cellular DNA damage. However, results from annexin V-propidium iodide (PI labeling and membrane polarization assays indicated disruption of the plasma membrane uncommon to apoptosis. These results provide evidence that secondary necrosis followed apoptosis. In addition, two human cancer cell lines were found to be infected by CPV. This necrotic event over apoptotic cell death and infection in human cells provide insightful information when developing CPV as a nanotool for cancer treatments.Keywords: canine parvovirus, apoptosis, necrosis, nanoparticle, virotherapy

  8. Modeling Insight into Battery Electrolyte Electrochemical Stability and Interfacial Structure.

    Science.gov (United States)

    Borodin, Oleg; Ren, Xiaoming; Vatamanu, Jenel; von Wald Cresce, Arthur; Knap, Jaroslaw; Xu, Kang

    2017-12-19

    Electroactive interfaces distinguish electrochemistry from chemistry and enable electrochemical energy devices like batteries, fuel cells, and electric double layer capacitors. In batteries, electrolytes should be either thermodynamically stable at the electrode interfaces or kinetically stable by forming an electronically insulating but ionically conducting interphase. In addition to a traditional optimization of electrolytes by adding cosolvents and sacrificial additives to preferentially reduce or oxidize at the electrode surfaces, knowledge of the local electrolyte composition and structure within the double layer as a function of voltage constitutes the basis of manipulating an interphase and expanding the operating windows of electrochemical devices. In this work, we focus on how the molecular-scale insight into the solvent and ion partitioning in the electrolyte double layer as a function of applied potential could predict changes in electrolyte stability and its initial oxidation and reduction reactions. In molecular dynamics (MD) simulations, highly concentrated lithium aqueous and nonaqueous electrolytes were found to exclude the solvent molecules from directly interacting with the positive electrode surface, which provides an additional mechanism for extending the electrolyte oxidation stability in addition to the well-established simple elimination of "free" solvent at high salt concentrations. We demonstrate that depending on their chemical structures, the anions could be designed to preferentially adsorb or desorb from the positive electrode with increasing electrode potential. This provides additional leverage to dictate the order of anion oxidation and to effectively select a sacrificial anion for decomposition. The opposite electrosorption behaviors of bis(trifluoromethane)sulfonimide (TFSI) and trifluoromethanesulfonate (OTF) as predicted by MD simulation in highly concentrated aqueous electrolytes were confirmed by surface enhanced infrared

  9. A Flexible Binding Site Architecture Provides New Insights into CcpA Global Regulation in Gram-Positive Bacteria.

    Science.gov (United States)

    Yang, Yunpeng; Zhang, Lu; Huang, He; Yang, Chen; Yang, Sheng; Gu, Yang; Jiang, Weihong

    2017-01-24

    Catabolite control protein A (CcpA) is the master regulator in Gram-positive bacteria that mediates carbon catabolite repression (CCR) and carbon catabolite activation (CCA), two fundamental regulatory mechanisms that enable competitive advantages in carbon catabolism. It is generally regarded that CcpA exerts its regulatory role by binding to a typical 14- to 16-nucleotide (nt) consensus site that is called a catabolite response element (cre) within the target regions. However, here we report a previously unknown noncanonical flexible architecture of the CcpA-binding site in solventogenic clostridia, providing new mechanistic insights into catabolite regulation. This novel CcpA-binding site, named cre var , has a unique architecture that consists of two inverted repeats and an intervening spacer, all of which are variable in nucleotide composition and length, except for a 6-bp core palindromic sequence (TGTAAA/TTTACA). It was found that the length of the intervening spacer of cre var can affect CcpA binding affinity, and moreover, the core palindromic sequence of cre var is the key structure for regulation. Such a variable architecture of cre var shows potential importance for CcpA's diverse and fine regulation. A total of 103 potential cre var sites were discovered in solventogenic Clostridium acetobutylicum, of which 42 sites were picked out for electrophoretic mobility shift assays (EMSAs), and 30 sites were confirmed to be bound by CcpA. These 30 cre var sites are associated with 27 genes involved in many important pathways. Also of significance, the cre var sites are found to be widespread and function in a great number of taxonomically different Gram-positive bacteria, including pathogens, suggesting their global role in Gram-positive bacteria. In Gram-positive bacteria, the global regulator CcpA controls a large number of important physiological and metabolic processes. Although a typical consensus CcpA-binding site, cre, has been identified, it remains

  10. Bring Your Own Device - Providing Reliable Model of Data Access

    Directory of Open Access Journals (Sweden)

    Stąpór Paweł

    2016-10-01

    Full Text Available The article presents a model of Bring Your Own Device (BYOD as a model network, which provides the user reliable access to network resources. BYOD is a model dynamically developing, which can be applied in many areas. Research network has been launched in order to carry out the test, in which as a service of BYOD model Work Folders service was used. This service allows the user to synchronize files between the device and the server. An access to the network is completed through the wireless communication by the 802.11n standard. Obtained results are shown and analyzed in this article.

  11. A multidisciplinary approach providing new insight into fruit flesh browning physiology in apple (Malus x domestica Borkh.).

    Science.gov (United States)

    Di Guardo, Mario; Tadiello, Alice; Farneti, Brian; Lorenz, Giorgia; Masuero, Domenico; Vrhovsek, Urska; Costa, Guglielmo; Velasco, Riccardo; Costa, Fabrizio

    2013-01-01

    In terms of the quality of minimally processed fruit, flesh browning is fundamentally important in the development of an aesthetically unpleasant appearance, with consequent off-flavours. The development of browning depends on the enzymatic action of the polyphenol oxidase (PPO). In the 'Golden Delicious' apple genome ten PPO genes were initially identified and located on three main chromosomes (2, 5 and 10). Of these genes, one element in particular, here called Md-PPO, located on chromosome 10, was further investigated and genetically mapped in two apple progenies ('Fuji x Pink Lady' and 'Golden Delicious x Braeburn'). Both linkage maps, made up of 481 and 608 markers respectively, were then employed to find QTL regions associated with fruit flesh browning, allowing the detection of 25 QTLs related to several browning parameters. These were distributed over six linkage groups with LOD values spanning from 3.08 to 4.99 and showed a rate of phenotypic variance from 26.1 to 38.6%. Anchoring of these intervals to the apple genome led to the identification of several genes involved in polyphenol synthesis and cell wall metabolism. Finally, the expression profile of two specific candidate genes, up and downstream of the polyphenolic pathway, namely phenylalanine ammonia lyase (PAL) and polyphenol oxidase (PPO), provided insight into flesh browning physiology. Md-PPO was further analyzed and two haplotypes were characterised and associated with fruit flesh browning in apple.

  12. Molecular details of secretory phospholipase A2 from flax (Linum usitatissimum L.) provide insight into its structure and function.

    Science.gov (United States)

    Gupta, Payal; Dash, Prasanta K

    2017-09-11

    Secretory phospholipase A 2 (sPLA 2 ) are low molecular weight proteins (12-18 kDa) involved in a suite of plant cellular processes imparting growth and development. With myriad roles in physiological and biochemical processes in plants, detailed analysis of sPLA 2 in flax/linseed is meagre. The present work, first in flax, embodies cloning, expression, purification and molecular characterisation of two distinct sPLA 2 s (I and II) from flax. PLA 2 activity of the cloned sPLA 2 s were biochemically assayed authenticating them as bona fide phospholipase A 2 . Physiochemical properties of both the sPLA 2 s revealed they are thermostable proteins requiring di-valent cations for optimum activity.While, structural analysis of both the proteins revealed deviations in the amino acid sequence at C- & N-terminal regions; hydropathic study revealed LusPLA 2 I as a hydrophobic protein and LusPLA 2 II as a hydrophilic protein. Structural analysis of flax sPLA 2 s revealed that secondary structure of both the proteins are dominated by α-helix followed by random coils. Modular superimposition of LusPLA 2 isoforms with rice sPLA 2 confirmed monomeric structural preservation among plant phospholipase A 2 and provided insight into structure of folded flax sPLA 2 s.

  13. A Multidisciplinary Approach Providing New Insight into Fruit Flesh Browning Physiology in Apple (Malus x domestica Borkh.)

    Science.gov (United States)

    Farneti, Brian; Lorenz, Giorgia; Masuero, Domenico; Vrhovsek, Urska; Costa, Guglielmo; Velasco, Riccardo; Costa, Fabrizio

    2013-01-01

    In terms of the quality of minimally processed fruit, flesh browning is fundamentally important in the development of an aesthetically unpleasant appearance, with consequent off-flavours. The development of browning depends on the enzymatic action of the polyphenol oxidase (PPO). In the ‘Golden Delicious’ apple genome ten PPO genes were initially identified and located on three main chromosomes (2, 5 and 10). Of these genes, one element in particular, here called Md-PPO, located on chromosome 10, was further investigated and genetically mapped in two apple progenies (‘Fuji x Pink Lady’ and ‘Golden Delicious x Braeburn’). Both linkage maps, made up of 481 and 608 markers respectively, were then employed to find QTL regions associated with fruit flesh browning, allowing the detection of 25 QTLs related to several browning parameters. These were distributed over six linkage groups with LOD values spanning from 3.08 to 4.99 and showed a rate of phenotypic variance from 26.1 to 38.6%. Anchoring of these intervals to the apple genome led to the identification of several genes involved in polyphenol synthesis and cell wall metabolism. Finally, the expression profile of two specific candidate genes, up and downstream of the polyphenolic pathway, namely phenylalanine ammonia lyase (PAL) and polyphenol oxidase (PPO), provided insight into flesh browning physiology. Md-PPO was further analyzed and two haplotypes were characterised and associated with fruit flesh browning in apple. PMID:24205065

  14. A Genomic Survey of SCPP Family Genes in Fishes Provides Novel Insights into the Evolution of Fish Scales.

    Science.gov (United States)

    Lv, Yunyun; Kawasaki, Kazuhiko; Li, Jia; Li, Yanping; Bian, Chao; Huang, Yu; You, Xinxin; Shi, Qiong

    2017-11-16

    The family of secretory calcium-binding phosphoproteins (SCPPs) have been considered vital to skeletal tissue mineralization. However, most previous SCPP studies focused on phylogenetically distant animals but not on those closely related species. Here we provide novel insights into the coevolution of SCPP genes and fish scales in 10 species from Otophysi . According to their scale phenotypes, these fishes can be divided into three groups, i.e., scaled, sparsely scaled, and scaleless. We identified homologous SCPP genes in the genomes of these species and revealed an absence of some SCPP members in some genomes, suggesting an uneven evolutionary history of SCPP genes in fishes. In addition, most of these SCPP genes, with the exception of SPP1 , individually form one or two gene cluster(s) on each corresponding genome. Furthermore, we constructed phylogenetic trees using maximum likelihood method to estimate their evolution. The phylogenetic topology mostly supports two subclasses in some species, such as Cyprinus carpio , Sinocyclocheilus anshuiensis , S. grahamin , and S. rhinocerous , but not in the other examined fishes. By comparing the gene structures of recently reported candidate genes, SCPP1 and SCPP5 , for determining scale phenotypes, we found that the hypothesis is suitable for Astyanax mexicanus , but denied by S. anshuiensis , even though they are both sparsely scaled for cave adaptation. Thus, we conclude that, although different fish species display similar scale phenotypes, the underlying genetic changes however might be diverse. In summary, this paper accelerates the recognition of the SCPP family in teleosts for potential scale evolution.

  15. Post-donation telephonic interview of blood donors providing an insight into delayed adverse reactions: First attempt in India.

    Science.gov (United States)

    Tiwari, Aseem K; Aggarwal, Geet; Dara, Ravi C; Arora, Dinesh; Srivastava, Khushboo; Raina, Vimarsh

    2017-04-01

    Blood donor experiences both immediate adverse reactions (IAR) and delayed adverse reactions (DAR). With limited published data available on the incidence of DAR, a study was conducted to estimate incidence and profile of DAR through telephonic interview. Study was conducted over a 45-day period for consecutive volunteer whole blood donations at tertiary care hospital. Donors were divided into first-time, repeat and regular and were monitored for IAR. They were given written copy of post-donation advice. Donors were contacted telephonically three weeks post-donation and enquired about general wellbeing and specific DAR in accordance with a standard n international (International Society of Blood Transfusion) standard format. Donors participated in the study of which 1.6% donors experienced an IAR. Much larger number reported DAR (10.3% vs.1.6% pdonors (age donors (>50 years). First time (12.3%) and repeat donors (13.5%) had similar frequency of DAR but were lower among regular donors (6.7%). DARs are more common than IAR and are of different profile. Post-donation interview has provided an insight into donor experiences and can be used as a valuable tool in donor hemovigilance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Independent Analysis of the Flagellum Surface and Matrix Proteomes Provides Insight into Flagellum Signaling in Mammalian-infectious Trypanosoma brucei*

    Science.gov (United States)

    Oberholzer, Michael; Langousis, Gerasimos; Nguyen, HoangKim T.; Saada, Edwin A.; Shimogawa, Michelle M.; Jonsson, Zophonias O.; Nguyen, Steven M.; Wohlschlegel, James A.; Hill, Kent L.

    2011-01-01

    The flagellum of African trypanosomes is an essential and multifunctional organelle that functions in motility, cell morphogenesis, and host-parasite interaction. Previous studies of the trypanosome flagellum have been limited by the inability to purify flagella without first removing the flagellar membrane. This limitation is particularly relevant in the context of studying flagellum signaling, as signaling requires surface-exposed proteins in the flagellar membrane and soluble signaling proteins in the flagellar matrix. Here we employ a combination of genetic and mechanical approaches to purify intact flagella from the African trypanosome, Trypanosoma brucei, in its mammalian-infectious stage. We combined flagellum purification with affinity-purification of surface-exposed proteins to conduct independent proteomic analyses of the flagellum surface and matrix fractions. The proteins identified encompass a broad range of molecular functionalities, including many predicted to function in signaling. Immunofluorescence and RNA interference studies demonstrate flagellum localization and function for proteins identified and provide insight into mechanisms of flagellum attachment and motility. The flagellum surface proteome includes many T. brucei-specific proteins and is enriched for proteins up-regulated in the mammalian-infectious stage of the parasite life-cycle. The combined results indicate that the flagellum surface presents a diverse and dynamic host-parasite interface that is well-suited for host-parasite signaling. PMID:21685506

  17. Transcriptomic analyses on muscle tissues of Litopenaeus vannamei provide the first profile insight into the response to low temperature stress.

    Directory of Open Access Journals (Sweden)

    Wen Huang

    Full Text Available The Pacific white shrimp (Litopenaeus vannamei is an important cultured crustacean species worldwide. However, little is known about the molecular mechanism of this species involved in the response to cold stress. In this study, four separate RNA-Seq libraries of L. vannamei were generated from 13°C stress and control temperature. Total 29,662 of Unigenes and overall of 19,619 annotated genes were obtained. Three comparisons were carried out among the four libraries, in which 72 of the top 20% of differentially-expressed genes were obtained, 15 GO and 5 KEGG temperature-sensitive pathways were fished out. Catalytic activity (GO: 0003824 and Metabolic pathways (ko01100 were the most annotated GO and KEGG pathways in response to cold stress, respectively. In addition, Calcium, MAPK cascade, Transcription factor and Serine/threonine-protein kinase signal pathway were picked out and clustered. Serine/threonine-protein kinase signal pathway might play more important roles in cold adaptation, while other three signal pathway were not widely transcribed. Our results had summarized the differentially-expressed genes and suggested the major important signaling pathways and related genes. These findings provide the first profile insight into the molecular basis of L. vannamei response to cold stress.

  18. Analysis of the Phlebiopsis gigantea Genome, Transcriptome and Secretome Provides Insight into Its Pioneer Colonization Strategies of Wood

    Science.gov (United States)

    Hori, Chiaki; Ishida, Takuya; Igarashi, Kiyohiko; Samejima, Masahiro; Suzuki, Hitoshi; Master, Emma; Ferreira, Patricia; Ruiz-Dueñas, Francisco J.; Held, Benjamin; Canessa, Paulo; Larrondo, Luis F.; Schmoll, Monika; Druzhinina, Irina S.; Kubicek, Christian P.; Gaskell, Jill A.; Kersten, Phil; St. John, Franz; Glasner, Jeremy; Sabat, Grzegorz; Splinter BonDurant, Sandra; Syed, Khajamohiddin; Yadav, Jagjit; Mgbeahuruike, Anthony C.; Kovalchuk, Andriy; Asiegbu, Fred O.; Lackner, Gerald; Hoffmeister, Dirk; Rencoret, Jorge; Gutiérrez, Ana; Sun, Hui; Lindquist, Erika; Barry, Kerrie; Riley, Robert; Grigoriev, Igor V.; Henrissat, Bernard; Kües, Ursula; Berka, Randy M.; Martínez, Angel T.; Covert, Sarah F.; Blanchette, Robert A.; Cullen, Daniel

    2014-01-01

    Collectively classified as white-rot fungi, certain basidiomycetes efficiently degrade the major structural polymers of wood cell walls. A small subset of these Agaricomycetes, exemplified by Phlebiopsis gigantea, is capable of colonizing freshly exposed conifer sapwood despite its high content of extractives, which retards the establishment of other fungal species. The mechanism(s) by which P. gigantea tolerates and metabolizes resinous compounds have not been explored. Here, we report the annotated P. gigantea genome and compare profiles of its transcriptome and secretome when cultured on fresh-cut versus solvent-extracted loblolly pine wood. The P. gigantea genome contains a conventional repertoire of hydrolase genes involved in cellulose/hemicellulose degradation, whose patterns of expression were relatively unperturbed by the absence of extractives. The expression of genes typically ascribed to lignin degradation was also largely unaffected. In contrast, genes likely involved in the transformation and detoxification of wood extractives were highly induced in its presence. Their products included an ABC transporter, lipases, cytochrome P450s, glutathione S-transferase and aldehyde dehydrogenase. Other regulated genes of unknown function and several constitutively expressed genes are also likely involved in P. gigantea's extractives metabolism. These results contribute to our fundamental understanding of pioneer colonization of conifer wood and provide insight into the diverse chemistries employed by fungi in carbon cycling processes. PMID:25474575

  19. Studies of the aggregation of mutant proteins in vitro provide insights into the genetics of amyloid diseases.

    Science.gov (United States)

    Chiti, Fabrizio; Calamai, Martino; Taddei, Niccolo; Stefani, Massimo; Ramponi, Giampietro; Dobson, Christopher M

    2002-12-10

    Protein aggregation and the formation of highly insoluble amyloid structures is associated with a range of debilitating human conditions, which include Alzheimer's disease, Parkinson's disease, and the Creutzfeldt-Jakob disease. Muscle acylphosphatase (AcP) has already provided significant insights into mutational changes that modulate amyloid formation. In the present paper, we have used this system to investigate the effects of mutations that modify the charge state of a protein without affecting significantly the hydrophobicity or secondary structural propensities of the polypeptide chain. A highly significant inverse correlation was found to exist between the rates of aggregation of the protein variants under denaturing conditions and their overall net charge. This result indicates that aggregation is generally favored by mutations that bring the net charge of the protein closer to neutrality. In light of this finding, we have analyzed natural mutations associated with familial forms of amyloid diseases that involve alteration of the net charge of the proteins or protein fragments associated with the diseases. Sixteen mutations have been identified for which the mechanism of action that causes the pathological condition is not yet known or fully understood. Remarkably, 14 of these 16 mutations cause the net charge of the corresponding peptide or protein that converts into amyloid deposits to be reduced. This result suggests that charge has been a key parameter in molecular evolution to ensure the avoidance of protein aggregation and identifies reduction of the net charge as an important determinant in at least some forms of protein deposition diseases.

  20. Discovery of cyclotides in the fabaceae plant family provides new insights into the cyclization, evolution, and distribution of circular proteins.

    Science.gov (United States)

    Poth, Aaron G; Colgrave, Michelle L; Philip, Reynold; Kerenga, Bomai; Daly, Norelle L; Anderson, Marilyn A; Craik, David J

    2011-04-15

    Cyclotides are plant proteins whose defining structural features are a head-to-tail cyclized backbone and three interlocking disulfide bonds, which in combination are known as a cyclic cystine knot. This unique structural motif confers cyclotides with exceptional resistance to proteolysis. Their endogenous function is thought to be as plant defense agents, associated with their insecticidal and larval growth-inhibitory properties. However, in addition, an array of pharmaceutically relevant biological activities has been ascribed to cyclotides, including anti-HIV, anthelmintic, uterotonic, and antimicrobial effects. So far, >150 cyclotides have been elucidated from members of the Rubiaceae, Violaceae, and Cucurbitaceae plant families, but their wider distribution among other plant families remains unclear. Clitoria ternatea (Butterfly pea) is a member of plant family Fabaceae and through its usage in traditional medicine to aid childbirth bears similarity to Oldenlandia affinis, from which many cyclotides have been isolated. Using a combination of nanospray and matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) analyses, we examined seed extracts of C. ternatea and discovered cyclotides in the Fabaceae, the third-largest family of flowering plants. We characterized 12 novel cyclotides, thus expanding knowledge of cyclotide distribution and evolution within the plant kingdom. The discovery of cyclotides containing novel sequence motifs near the in planta cyclization site has provided new insights into cyclotide biosynthesis. In particular, MS analyses of the novel cyclotides from C. ternatea suggest that Asn to Asp variants at the cyclization site are more common than previously recognized. Moreover, this study provides impetus for the examination of other economically and agriculturally significant species within Fabaceae, now the largest plant family from which cyclotides have been described.

  1. Whole Genome Sequencing of Mycobacterium africanum Strains from Mali Provides Insights into the Mechanisms of Geographic Restriction.

    Science.gov (United States)

    Winglee, Kathryn; Manson McGuire, Abigail; Maiga, Mamoudou; Abeel, Thomas; Shea, Terrance; Desjardins, Christopher A; Diarra, Bassirou; Baya, Bocar; Sanogo, Moumine; Diallo, Souleymane; Earl, Ashlee M; Bishai, William R

    2016-01-01

    Mycobacterium africanum, made up of lineages 5 and 6 within the Mycobacterium tuberculosis complex (MTC), causes up to half of all tuberculosis cases in West Africa, but is rarely found outside of this region. The reasons for this geographical restriction remain unknown. Possible reasons include a geographically restricted animal reservoir, a unique preference for hosts of West African ethnicity, and an inability to compete with other lineages outside of West Africa. These latter two hypotheses could be caused by loss of fitness or altered interactions with the host immune system. We sequenced 92 MTC clinical isolates from Mali, including two lineage 5 and 24 lineage 6 strains. Our genome sequencing assembly, alignment, phylogeny and average nucleotide identity analyses enabled us to identify features that typify lineages 5 and 6 and made clear that these lineages do not constitute a distinct species within the MTC. We found that in Mali, lineage 6 and lineage 4 strains have similar levels of diversity and evolve drug resistance through similar mechanisms. In the process, we identified a putative novel streptomycin resistance mutation. In addition, we found evidence of person-to-person transmission of lineage 6 isolates and showed that lineage 6 is not enriched for mutations in virulence-associated genes. This is the largest collection of lineage 5 and 6 whole genome sequences to date, and our assembly and alignment data provide valuable insights into what distinguishes these lineages from other MTC lineages. Lineages 5 and 6 do not appear to be geographically restricted due to an inability to transmit between West African hosts or to an elevated number of mutations in virulence-associated genes. However, lineage-specific mutations, such as mutations in cell wall structure, secretion systems and cofactor biosynthesis, provide alternative mechanisms that may lead to host specificity.

  2. Levels of Interaction Provided by Online Distance Education Models

    Science.gov (United States)

    Alhih, Mohammed; Ossiannilsson, Ebba; Berigel, Muhammet

    2017-01-01

    Interaction plays a significant role to foster usability and quality in online education. It is one of the quality standard to reveal the evidence of practice in online distance education models. This research study aims to evaluate levels of interaction in the practices of distance education centres. It is aimed to provide online distance…

  3. Zebrafish Models of Human Leukemia: Technological Advances and Mechanistic Insights.

    Science.gov (United States)

    Harrison, Nicholas R; Laroche, Fabrice J F; Gutierrez, Alejandro; Feng, Hui

    2016-01-01

    Insights concerning leukemic pathophysiology have been acquired in various animal models and further efforts to understand the mechanisms underlying leukemic treatment resistance and disease relapse promise to improve therapeutic strategies. The zebrafish (Danio rerio) is a vertebrate organism with a conserved hematopoietic program and unique experimental strengths suiting it for the investigation of human leukemia. Recent technological advances in zebrafish research including efficient transgenesis, precise genome editing, and straightforward transplantation techniques have led to the generation of a number of leukemia models. The transparency of the zebrafish when coupled with improved lineage-tracing and imaging techniques has revealed exquisite details of leukemic initiation, progression, and regression. With these advantages, the zebrafish represents a unique experimental system for leukemic research and additionally, advances in zebrafish-based high-throughput drug screening promise to hasten the discovery of novel leukemia therapeutics. To date, investigators have accumulated knowledge of the genetic underpinnings critical to leukemic transformation and treatment resistance and without doubt, zebrafish are rapidly expanding our understanding of disease mechanisms and helping to shape therapeutic strategies for improved outcomes in leukemic patients.

  4. The state of multiple sclerosis: current insight into the patient/health care provider relationship, treatment challenges, and satisfaction

    Directory of Open Access Journals (Sweden)

    Tintoré M

    2016-12-01

    Full Text Available Mar Tintoré,1 Maggie Alexander,2 Kathleen Costello,3 Martin Duddy,4 David E Jones,5 Nancy Law,6 Gilmore O’Neill,7 Antonio Uccelli,8 Robert Weissert,9 Sibyl Wray10 1Multiple Sclerosis Centre of Catalonia, Hospital Vall d’Hebron, Barcelona, Spain; 2European Multiple Sclerosis Platform, Brussels, Belgium; 3National Multiple Sclerosis Society, Denver, CO, USA; 4Royal Victoria Infirmary, Newcastle-upon-Tyne, UK; 5Department of Neurology, University of Virginia, Charlottesville, VA, USA; 6Nancy Law Consulting LLC, Parker, CO, USA; 7Biogen, Cambridge, MA, USA; 8Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; 9Department of Neurology, University of Regensburg, Regensburg, Germany; 10Hope Neurology Multiple Sclerosis Center, Knoxville, TN, USA Background: Managing multiple sclerosis (MS treatment presents challenges for both patients and health care professionals. Effective communication between patients with MS and their neurologist is important for improving clinical outcomes and quality of life. Methods: A closed-ended online market research survey was used to assess the current state of MS care from the perspective of both patients with MS (≥18 years of age and neurologists who treat MS from Europe and the US and to gain insight into perceptions of treatment expectations/goals, treatment decisions, treatment challenges, communication, and satisfaction with care, based on current clinical practice. Results: A total of 900 neurologists and 982 patients completed the survey, of whom 46% self-identified as having remitting-relapsing MS, 29% secondary progressive MS, and 11% primary progressive MS. Overall, patients felt satisfied with their disease-modifying therapy (DMT; satisfaction related to comfort in speaking with their neurologist and participation in their DMT decision-making process. Patients who self-identified as having relapsing-remitting MS were more likely to be very satisfied with their treatment

  5. Structural and mutational analysis of Escherichia coli AlkB provides insight into substrate specificity and DNA damage searching.

    Directory of Open Access Journals (Sweden)

    Paul J Holland

    Full Text Available BACKGROUND: In Escherichia coli, cytotoxic DNA methyl lesions on the N1 position of purines and N3 position of pyrimidines are primarily repaired by the 2-oxoglutarate (2-OG iron(II dependent dioxygenase, AlkB. AlkB repairs 1-methyladenine (1-meA and 3-methylcytosine (3-meC lesions, but it also repairs 1-methylguanine (1-meG and 3-methylthymine (3-meT at a much less efficient rate. How the AlkB enzyme is able to locate and identify methylated bases in ssDNA has remained an open question. METHODOLOGY/PRINCIPAL FINDINGS: We determined the crystal structures of the E. coli AlkB protein holoenzyme and the AlkB-ssDNA complex containing a 1-meG lesion. We coupled this to site-directed mutagenesis of amino acids in and around the active site, and tested the effects of these mutations on the ability of the protein to bind both damaged and undamaged DNA, as well as catalyze repair of a methylated substrate. CONCLUSIONS/SIGNIFICANCE: A comparison of our substrate-bound AlkB-ssDNA complex with our unliganded holoenzyme reveals conformational changes of residues within the active site that are important for binding damaged bases. Site-directed mutagenesis of these residues reveals novel insight into their roles in DNA damage recognition and repair. Our data support a model that the AlkB protein utilizes at least two distinct conformations in searching and binding methylated bases within DNA: a "searching" mode and "repair" mode. Moreover, we are able to functionally separate these modes through mutagenesis of residues that affect one or the other binding state. Finally, our mutagenesis experiments show that amino acid D135 of AlkB participates in both substrate specificity and catalysis.

  6. A Flexible Binding Site Architecture Provides New Insights into CcpA Global Regulation in Gram-Positive Bacteria

    Directory of Open Access Journals (Sweden)

    Yunpeng Yang

    2017-01-01

    Full Text Available Catabolite control protein A (CcpA is the master regulator in Gram-positive bacteria that mediates carbon catabolite repression (CCR and carbon catabolite activation (CCA, two fundamental regulatory mechanisms that enable competitive advantages in carbon catabolism. It is generally regarded that CcpA exerts its regulatory role by binding to a typical 14- to 16-nucleotide (nt consensus site that is called a catabolite response element (cre within the target regions. However, here we report a previously unknown noncanonical flexible architecture of the CcpA-binding site in solventogenic clostridia, providing new mechanistic insights into catabolite regulation. This novel CcpA-binding site, named crevar, has a unique architecture that consists of two inverted repeats and an intervening spacer, all of which are variable in nucleotide composition and length, except for a 6-bp core palindromic sequence (TGTAAA/TTTACA. It was found that the length of the intervening spacer of crevar can affect CcpA binding affinity, and moreover, the core palindromic sequence of crevar is the key structure for regulation. Such a variable architecture of crevar shows potential importance for CcpA’s diverse and fine regulation. A total of 103 potential crevar sites were discovered in solventogenic Clostridium acetobutylicum, of which 42 sites were picked out for electrophoretic mobility shift assays (EMSAs, and 30 sites were confirmed to be bound by CcpA. These 30 crevar sites are associated with 27 genes involved in many important pathways. Also of significance, the crevar sites are found to be widespread and function in a great number of taxonomically different Gram-positive bacteria, including pathogens, suggesting their global role in Gram-positive bacteria.

  7. Comparative proteomic study on Brassica hexaploid and its parents provides new insights into the effects of polyploidization.

    Science.gov (United States)

    Shen, Yanyue; Zhang, Yu; Zou, Jun; Meng, Jinling; Wang, Jianbo

    2015-01-01

    Polyploidy has played an important role in promoting plant evolution through genomic merging and doubling. Although genomic and transcriptomic changes have been observed in polyploids, the effects of polyploidization on proteomic divergence are poorly understood. In this study, we reported quantitative analysis of proteomic changes in leaves of Brassica hexaploid and its parents using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with mass spectrometry. A total of 2044 reproducible proteins were quantified by at least two unique peptides. We detected 452 proteins differentially expressed between Brassica hexaploid and its parents, and 100 proteins were non-additively expressed in Brassica hexaploid, which suggested a trend of non-additive protein regulation following genomic merger and doubling. Functional categories of cellular component biogenesis, immune system process, and response to stimulus, were significantly enriched in non-additive proteins, probably providing a driving force for variation and adaptation in allopolyploids. In particular, majority of the total 452 differentially expressed proteins showed expression level dominance of one parental expression, and there was an expression level dominance bias toward the tetraploid progenitor. In addition, the percentage of differentially expressed proteins that matched previously reported differentially genes were relatively low. This study aimed to get new insights into the effects of polyploidization on proteomic divergence. Using iTRAQ LC-MS/MS technology, we identified 452 differentially expressed proteins between allopolyploid and its parents which involved in response to stimulus, multi-organism process, and immune system process, much more than previous studies using 2-DE coupled with mass spectrometry technology. Therefore, our manuscript represents the most comprehensive analysis of protein profiles in allopolyploid and its parents, which will lead to a better understanding of

  8. The relationship of transverse sinus stenosis to bony groove dimensions provides an insight into the aetiology of idiopathic intracranial hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Connor, S.E.J.; Stewart, V.R.; O' Flynn, E.A.M. [King' s College Hospital, Neuroradiology Department, Ruskin Wing, London (United Kingdom); Siddiqui, M.A. [Southern General Hospital, Institute of Neurological Sciences, Glasgow (United Kingdom)

    2008-12-15

    Transverse sinus tapered narrowings are frequently identified in patients with idiopathic intracranial hypertension (IIH); however, it remains unclear whether they are primary stenoses or whether they occur secondary to raised cerebrospinal fluid pressure. Computed tomographic venography demonstrates both the morphology of the venous system and the adjacent bony grooves so it may provide an insight into the aetiology of these transverse sinus stenoses. Tapered transverse sinus narrowings (>50%) were studied in 19 patients without IIH and 14 patients with IIH. Computed tomography vascular studies were reviewed and the dimensions of the venous sinuses and bony grooves at the sites of maximum and minimum transverse sinus area dimensions were recorded. There was demonstrated to be a strong correlation of bony groove height with venous sinus height at the largest portions of the transverse sinus in both IIH patients and non-IIH subjects as well as at the transverse sinus narrowing in non-IIH subjects. There was a discordant relationship between bony groove height and venous sinus height at the site of transverse sinus stenoses in IIH patients. In 5/23 IIH transverse sinus stenoses, the bony groove height was proportionate to that seen in non-IIH subjects. There were a further 8/23 cases where the small or absent sinus was associated with an absent bony groove. Transverse sinus tapered narrowings in subjects without IIH and in the majority of patients with IIH were associated with proportionately small or absent grooves, and these are postulated to be primary or fixed. Some patients with IIH demonstrate tapered transverse sinus stenoses with disproportionately large bony grooves, suggesting a secondary or acquired narrowing. This implies a varied aetiology for the transverse sinus stenoses of IIH. (orig.)

  9. Molecular characterization of Babesia peircei and Babesia ugwidiensis provides insight into the evolution and host specificity of avian piroplasmids

    Directory of Open Access Journals (Sweden)

    Michael J. Yabsley

    2017-12-01

    Full Text Available There are 16 recognized species of avian-infecting Babesia spp. (Piroplasmida: Babesiidae. While the classification of piroplasmids has been historically based on morphological differences, geographic isolation and presumed host and/or vector specificities, recent studies employing gene sequence analysis have provided insight into their phylogenetic relationships and host distribution and specificity. In this study, we analyzed the sequences of the 18S rRNA gene and ITS-1 and ITS-2 regions of two Babesia species from South African seabirds: Babesia peircei from African penguins (Spheniscus demersus and Babesia ugwidiensis from Bank and Cape cormorants (Phalacrocorax neglectus and P. capensis, respectively. Our results show that avian Babesia spp. are not monophyletic, with at least three distinct phylogenetic groups. B. peircei and B. ugwidiensis are closely related, and fall within the same phylogenetic group as B. ardeae (from herons Ardea cinerea, B. poelea (from boobies Sula spp. and B. uriae (from murres Uria aalge. The validity of B. peircei and B. ugwidiensis as separate species is corroborated by both morphological and genetic evidence. On the other hand, our results indicate that B. poelea might be a synonym of B. peircei, which in turn would be a host generalist that infects seabirds from multiple orders. Further studies combining morphological and molecular methods are warranted to clarify the taxonomy, phylogeny and host distribution of avian piroplasmids. Keywords: Africa, Babesia, Piroplasmida, Phalacrocoracidae, Spheniscidae, Tick-borne pathogen

  10. The state of multiple sclerosis: current insight into the patient/health care provider relationship, treatment challenges, and satisfaction

    Science.gov (United States)

    Tintoré, Mar; Alexander, Maggie; Costello, Kathleen; Duddy, Martin; Jones, David E; Law, Nancy; O’Neill, Gilmore; Uccelli, Antonio; Weissert, Robert; Wray, Sibyl

    2017-01-01

    Background Managing multiple sclerosis (MS) treatment presents challenges for both patients and health care professionals. Effective communication between patients with MS and their neurologist is important for improving clinical outcomes and quality of life. Methods A closed-ended online market research survey was used to assess the current state of MS care from the perspective of both patients with MS (≥18 years of age) and neurologists who treat MS from Europe and the US and to gain insight into perceptions of treatment expectations/goals, treatment decisions, treatment challenges, communication, and satisfaction with care, based on current clinical practice. Results A total of 900 neurologists and 982 patients completed the survey, of whom 46% self-identified as having remitting-relapsing MS, 29% secondary progressive MS, and 11% primary progressive MS. Overall, patients felt satisfied with their disease-modifying therapy (DMT); satisfaction related to comfort in speaking with their neurologist and participation in their DMT decision-making process. Patients who self-identified as having relapsing-remitting MS were more likely to be very satisfied with their treatment. Top challenges identified by patients in managing their DMT were cost, side effects/tolerability of treatment, and uncertainty if treatment was working. Half of the patients reported skipping doses, but only 68% told their health care provider that they did so. Conclusion Several important differences in perception were identified between patients and neurologists concerning treatment selection, satisfaction, expectations, goals, and comfort discussing symptoms, as well as treatment challenges and skipped doses. The study results emphasize that patient/neurologist communication and patient input into the treatment decision-making process likely influence patient satisfaction with treatment. PMID:28053511

  11. The state of multiple sclerosis: current insight into the patient/health care provider relationship, treatment challenges, and satisfaction.

    Science.gov (United States)

    Tintoré, Mar; Alexander, Maggie; Costello, Kathleen; Duddy, Martin; Jones, David E; Law, Nancy; O'Neill, Gilmore; Uccelli, Antonio; Weissert, Robert; Wray, Sibyl

    2017-01-01

    Managing multiple sclerosis (MS) treatment presents challenges for both patients and health care professionals. Effective communication between patients with MS and their neurologist is important for improving clinical outcomes and quality of life. A closed-ended online market research survey was used to assess the current state of MS care from the perspective of both patients with MS (≥18 years of age) and neurologists who treat MS from Europe and the US and to gain insight into perceptions of treatment expectations/goals, treatment decisions, treatment challenges, communication, and satisfaction with care, based on current clinical practice. A total of 900 neurologists and 982 patients completed the survey, of whom 46% self-identified as having remitting-relapsing MS, 29% secondary progressive MS, and 11% primary progressive MS. Overall, patients felt satisfied with their disease-modifying therapy (DMT); satisfaction related to comfort in speaking with their neurologist and participation in their DMT decision-making process. Patients who self-identified as having relapsing-remitting MS were more likely to be very satisfied with their treatment. Top challenges identified by patients in managing their DMT were cost, side effects/tolerability of treatment, and uncertainty if treatment was working. Half of the patients reported skipping doses, but only 68% told their health care provider that they did so. Several important differences in perception were identified between patients and neurologists concerning treatment selection, satisfaction, expectations, goals, and comfort discussing symptoms, as well as treatment challenges and skipped doses. The study results emphasize that patient/neurologist communication and patient input into the treatment decision-making process likely influence patient satisfaction with treatment.

  12. The relationship of transverse sinus stenosis to bony groove dimensions provides an insight into the aetiology of idiopathic intracranial hypertension

    International Nuclear Information System (INIS)

    Connor, S.E.J.; Stewart, V.R.; O'Flynn, E.A.M.; Siddiqui, M.A.

    2008-01-01

    Transverse sinus tapered narrowings are frequently identified in patients with idiopathic intracranial hypertension (IIH); however, it remains unclear whether they are primary stenoses or whether they occur secondary to raised cerebrospinal fluid pressure. Computed tomographic venography demonstrates both the morphology of the venous system and the adjacent bony grooves so it may provide an insight into the aetiology of these transverse sinus stenoses. Tapered transverse sinus narrowings (>50%) were studied in 19 patients without IIH and 14 patients with IIH. Computed tomography vascular studies were reviewed and the dimensions of the venous sinuses and bony grooves at the sites of maximum and minimum transverse sinus area dimensions were recorded. There was demonstrated to be a strong correlation of bony groove height with venous sinus height at the largest portions of the transverse sinus in both IIH patients and non-IIH subjects as well as at the transverse sinus narrowing in non-IIH subjects. There was a discordant relationship between bony groove height and venous sinus height at the site of transverse sinus stenoses in IIH patients. In 5/23 IIH transverse sinus stenoses, the bony groove height was proportionate to that seen in non-IIH subjects. There were a further 8/23 cases where the small or absent sinus was associated with an absent bony groove. Transverse sinus tapered narrowings in subjects without IIH and in the majority of patients with IIH were associated with proportionately small or absent grooves, and these are postulated to be primary or fixed. Some patients with IIH demonstrate tapered transverse sinus stenoses with disproportionately large bony grooves, suggesting a secondary or acquired narrowing. This implies a varied aetiology for the transverse sinus stenoses of IIH. (orig.)

  13. Integrated application of transcriptomics and metabolomics provides insights into glycogen content regulation in the Pacific oyster Crassostrea gigas.

    Science.gov (United States)

    Li, Busu; Song, Kai; Meng, Jie; Li, Li; Zhang, Guofan

    2017-09-11

    stress. These findings will not only provide insights into the molecular mechanisms underlying oyster quality, but also promote research into the molecular breeding of oysters.

  14. Community proteomics provides functional insight into polyhydroxyalkanoate production by a mixed microbial culture cultivated on fermented dairy manure.

    Science.gov (United States)

    Hanson, Andrea J; Guho, Nicholas M; Paszczynski, Andrzej J; Coats, Erik R

    2016-09-01

    Polyhydroxyalkanoates (PHAs) are bio-based, biodegradable polyesters that can be produced from organic-rich waste streams using mixed microbial cultures (MMCs). To maximize PHA production, MMCs are enriched for bacteria with a high polymer storage capacity through the application of aerobic dynamic feeding (ADF) in a sequencing batch reactor (SBR), which consequently induces a feast-famine metabolic response. Though the feast-famine response is generally understood empirically at a macro-level, the molecular level is less refined. The objective of this study was to investigate the microbial community composition and proteome profile of an enriched MMC cultivated on fermented dairy manure. The enriched MMC exhibited a feast-famine response and was capable of producing up to 40 % (wt. basis) PHA in a fed-batch reactor. High-throughput 16S rRNA gene sequencing revealed a microbial community dominated by Meganema, a known PHA-producing genus not often observed in high abundance in enrichment SBRs. The application of the proteomic methods two-dimensional electrophoresis and LC-MS/MS revealed PHA synthesis, energy generation, and protein synthesis prominently occurring during the feast phase, corroborating bulk solution variable observations and theoretical expectations. During the famine phase, nutrient transport, acyl-CoA metabolism, additional energy generation, and housekeeping functions were more pronounced, informing previously under-determined MMC functionality under famine conditions. During fed-batch PHA production, acetyl-CoA acetyltransferase and PHA granule-bound phasin proteins were in increased abundance relative to the SBR, supporting the higher PHA content observed. Collectively, the results provide unique microbial community structural and functional insight into feast-famine PHA production from waste feedstocks using MMCs.

  15. Modeling Double Subjectivity for Gaining Programmable Insights: Framing the Case of Uber

    Directory of Open Access Journals (Sweden)

    Loretta Henderson Cheeks

    2017-09-01

    Full Text Available The Internet is the premier platform that enable the emergence of new technologies. Online news is unstructured narrative text that embeds facts, frames, and amplification that can influence society attitudes about technology adoption. Online news sources are carriers of voluminous amounts of news for reaching significantly large audience and have no geographical or time boundaries. The interplay of complex and dynamical forces among authors and readers allow for progressive emergent and latent properties to exhibit. Our concept of “Double subjectivity” provides a new paradigm for exploring complementary programmable insights of deeply buried meanings in a system. The ability to understand internal embeddedness in a large collection of related articles are beyond the reach of existing computational tools, and are hence left to human readers with unscalable results. This paper uncovers the potential to utilize advanced machine learning in a new way to automate the understanding of implicit structures and their associated latent meanings to give an early human-level insight into emergent technologies, with a concrete example of “Uber”. This paper establishes the new concept of double subjectivity as an instrument for large-scale machining of unstructured text and introduces a social influence model for the discovery of distinct pathways into emerging technology, and hence an insight. The programmable insight reveals early spatial and temporal opinion shift monitoring in complex networks in a structured way for computational treatment and visualization.

  16. A Model for the Growth of Network Service Providers

    Science.gov (United States)

    2011-12-01

    Service Provider O-D Origin-Destination POP Point of Presence UCG Unilateral Connection Game xiv THIS PAGE INTENTIONALLY LEFT BLANK xv EXECUTIVE...xvi We make use of the Abilene dataset as input to the network provisioning model and assume that the NSP is new to the market and is building an...has to decide on the connections to build and the markets to serve in order to maximize its profits. The NSP makes these decisions based on the market

  17. Model of Providing Assistive Technologies in Special Education Schools.

    Science.gov (United States)

    Lersilp, Suchitporn; Putthinoi, Supawadee; Chakpitak, Nopasit

    2015-05-14

    Most students diagnosed with disabilities in Thai special education schools received assistive technologies, but this did not guarantee the greatest benefits. The purpose of this study was to survey the provision, use and needs of assistive technologies, as well as the perspectives of key informants regarding a model of providing them in special education schools. The participants were selected by the purposive sampling method, and they comprised 120 students with visual, physical, hearing or intellectual disabilities from four special education schools in Chiang Mai, Thailand; and 24 key informants such as parents or caregivers, teachers, school principals and school therapists. The instruments consisted of an assistive technology checklist and a semi-structured interview. Results showed that a category of assistive technologies was provided for students with disabilities, with the highest being "services", followed by "media" and then "facilities". Furthermore, mostly students with physical disabilities were provided with assistive technologies, but those with visual disabilities needed it more. Finally, the model of providing assistive technologies was composed of 5 components: Collaboration; Holistic perspective; Independent management of schools; Learning systems and a production manual for users; and Development of an assistive technology center, driven by 3 major sources such as Government and Private organizations, and Schools.

  18. Success of mainstream partial nitritation/anammox demands integration of engineering, microbiome and modeling insights.

    Science.gov (United States)

    Agrawal, Shelesh; Seuntjens, Dries; Cocker, Pieter De; Lackner, Susanne; Vlaeminck, Siegfried E

    2018-04-01

    Twenty years ago, mainstream partial nitritation/anammox (PN/A) was conceptually proposed as pivotal for a more sustainable treatment of municipal wastewater. Its economic potential spurred research, yet practice awaits a comprehensive recipe for microbial resource management. Implementing mainstream PN/A requires transferable and operable ways to steer microbial competition as to meet discharge requirements on a year-round basis at satisfactory conversion rates. In essence, the competition for nitrogen, organic carbon and oxygen is grouped into 'ON/OFF' (suppression/promotion) and 'IN/OUT' (wash-out/retention and seeding) strategies, selecting for desirable conversions and microbes. Some insights need mechanistic understanding, while empirical observations suffice elsewhere. The provided methodological R&D framework integrates insights in engineering, microbiome and modeling. Such synergism should catalyze the implementation of energy-positive sewage treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Modelling catchment areas for secondary care providers: a case study.

    Science.gov (United States)

    Jones, Simon; Wardlaw, Jessica; Crouch, Susan; Carolan, Michelle

    2011-09-01

    Hospitals need to understand patient flows in an increasingly competitive health economy. New initiatives like Patient Choice and the Darzi Review further increase this demand. Essential to understanding patient flows are demographic and geographic profiles of health care service providers, known as 'catchment areas' and 'catchment populations'. This information helps Primary Care Trusts (PCTs) to review how their populations are accessing services, measure inequalities and commission services; likewise it assists Secondary Care Providers (SCPs) to measure and assess potential gains in market share, redesign services, evaluate admission thresholds and plan financial budgets. Unlike PCTs, SCPs do not operate within fixed geographic boundaries. Traditionally, SCPs have used administrative boundaries or arbitrary drive times to model catchment areas. Neither approach satisfactorily represents current patient flows. Furthermore, these techniques are time-consuming and can be challenging for healthcare managers to exploit. This paper presents three different approaches to define catchment areas, each more detailed than the previous method. The first approach 'First Past the Post' defines catchment areas by allocating a dominant SCP to each Census Output Area (OA). The SCP with the highest proportion of activity within each OA is considered the dominant SCP. The second approach 'Proportional Flow' allocates activity proportionally to each OA. This approach allows for cross-boundary flows to be captured in a catchment area. The third and final approach uses a gravity model to define a catchment area, which incorporates drive or travel time into the analysis. Comparing approaches helps healthcare providers to understand whether using more traditional and simplistic approaches to define catchment areas and populations achieves the same or similar results as complex mathematical modelling. This paper has demonstrated, using a case study of Manchester, that when estimating

  20. Unique genome organization of non-mammalian papillomaviruses provides insights into the evolution of viral early proteins.

    Science.gov (United States)

    Van Doorslaer, Koenraad; Ruoppolo, Valeria; Schmidt, Annie; Lescroël, Amelie; Jongsomjit, Dennis; Elrod, Megan; Kraberger, Simona; Stainton, Daisy; Dugger, Katie M; Ballard, Grant; Ainley, David G; Varsani, Arvind

    2017-07-01

    estimated the divergence time between Northern fulmar-associated papillomavirus and the other Sauropsid papillomaviruses be to around 250 million years ago, during the Paleozoic-Mesozoic transition and our analysis dates the root of the papillomavirus tree between 400 and 600 million years ago. Our analysis shows evidence for niche adaptation and that these non-mammalian viruses have highly divergent E6 and E7 proteins, providing insights into the evolution of the early viral (onco-)proteins.

  1. Unique genome organization of non-mammalian papillomaviruses provides insights into the evolution of viral early proteins

    Science.gov (United States)

    Van Doorslaer, Koenraad; Ruoppolo, Valeria; Schmidt, Annie; Lescroël, Amelie; Jongsomjit, Dennis; Elrod, Megan; Kraberger, Simona; Stainton, Daisy; Dugger, Katie M.; Ballard, Grant; Ainley, David G.; Varsani, Arvind

    2017-01-01

    divergence time between Northern fulmar-associated papillomavirus and the other Sauropsid papillomaviruses be to around 250 million years ago, during the Paleozoic-Mesozoic transition and our analysis dates the root of the papillomavirus tree between 400 and 600 million years ago. Our analysis shows evidence for niche adaptation and that these non-mammalian viruses have highly divergent E6 and E7 proteins, providing insights into the evolution of the early viral (onco-)proteins.

  2. Geochemistry and travertine dating provide new insights into the hydrogeology of the Great Artesian Basin, South Australia

    International Nuclear Information System (INIS)

    Love, A.J.; Rousseau-Gueutin, P.; Priestley, S.; Keppel, M.; Shand, P.; Karlstrom, K.; Crossey, L.; Wholing, D.; Fulton, S.

    2013-01-01

    While of great national and societal significance, and importance in its own right, the Great Artesian Basin of Australia is an iconic example of a continental scale artesian groundwater system. New geochemical, hydrological, and neo-tectonic data suggests that existing models that involve recharge in eastern Australia, relatively simple flow paths and discharge in springs in the western margin require modification. New geochemical data indicate a small volume flux of deeply derived (endogenic) fluids mixing into the aquifer system at a continental scale. Neotectonic data indicates active tectonism today that provides a fluid pathway through faults for the deeply sourced endogenic fluids to discharge in GAB travertine depositing springs. (authors)

  3. Reactor pressure vessel embrittlement: Insights from neural network modelling

    Science.gov (United States)

    Mathew, J.; Parfitt, D.; Wilford, K.; Riddle, N.; Alamaniotis, M.; Chroneos, A.; Fitzpatrick, M. E.

    2018-04-01

    Irradiation embrittlement of steel pressure vessels is an important consideration for the operation of current and future light water nuclear reactors. In this study we employ an ensemble of artificial neural networks in order to provide predictions of the embrittlement using two literature datasets, one based on US surveillance data and the second from the IVAR experiment. We use these networks to examine trends with input variables and to assess various literature models including compositional effects and the role of flux and temperature. Overall, the networks agree with the existing literature models and we comment on their more general use in predicting irradiation embrittlement.

  4. Standardized Profiling of The Membrane-Enriched Proteome of Mouse Dorsal Root Ganglia (DRG) Provides Novel Insights Into Chronic Pain.

    Science.gov (United States)

    Rouwette, Tom; Sondermann, Julia; Avenali, Luca; Gomez-Varela, David; Schmidt, Manuela

    2016-06-01

    Chronic pain is a complex disease with limited treatment options. Several profiling efforts have been employed with the aim to dissect its molecular underpinnings. However, generated results are often inconsistent and nonoverlapping, which is largely because of inherent technical constraints. Emerging data-independent acquisition (DIA)-mass spectrometry (MS) has the potential to provide unbiased, reproducible and quantitative proteome maps - a prerequisite for standardization among experiments. Here, we designed a DIA-based proteomics workflow to profile changes in the abundance of dorsal root ganglia (DRG) proteins in two mouse models of chronic pain, inflammatory and neuropathic. We generated a DRG-specific spectral library containing 3067 DRG proteins, which enables their standardized quantification by means of DIA-MS in any laboratory. Using this resource, we profiled 2526 DRG proteins in each biological replicate of both chronic pain models and respective controls with unprecedented reproducibility. We detected numerous differentially regulated proteins, the majority of which exhibited pain model-specificity. Our approach recapitulates known biology and discovers dozens of proteins that have not been characterized in the somatosensory system before. Functional validation experiments and analysis of mouse pain behaviors demonstrate that indeed meaningful protein alterations were discovered. These results illustrate how the application of DIA-MS can open new avenues to achieve the long-awaited standardization in the molecular dissection of pathologies of the somatosensory system. Therefore, our findings provide a valuable framework to qualitatively extend our understanding of chronic pain and somatosensation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Implementation of physiological fluids to provide insight into the characterization, fate, and biological interactions of silver nanoparticles

    Science.gov (United States)

    Breitner, Emily K.; Burns, Katherine E.; Hussain, Saber M.; Comfort, Kristen K.

    2018-06-01

    Silver nanoparticles (AgNPs) are being increasingly utilized in consumer and medical applications. However, there remains conflicting reports on their safety, which are evaluated through a combination of in vitro and in vivo exposure models. These discrepancies may arise, in part, due to the inherent differences between cell-based and animal systems. It is well established that nanotoxicological effects are highly dependent on the unique physicochemical properties and behavior of the particle set, including size, surface chemistry, agglomeration, and ionic dissolution. However, recent studies have identified that these properties vary as a function of exposure environment; providing a rationale for the contradictory results between in vitro and in vivo assessments. Artificial physiological fluids are emerging as a powerful tool as they allow for the characterization of NPs in an environment which they would likely encounter in vivo, in addition to having the experimental advantages of flexibility and consistency. Here, we demonstrated that the utilization of artificial fluids provided a mechanism to assess AgNP behavior and induced bioresponses in environments that they would likely encounter in vivo. AgNPs were introduced within an alveolar-based exposure model, which included alveolar epithelial (A549) cells incubated within artificial alveolar fluid (AF). Additionally, the particles underwent extensive characterization within both AF and lysosomal fluid, which the AgNPs would encounter following cellular internalization. Following incubation in physiological environments AgNP properties were significantly modified versus a traditional media environment, including alterations to both extent of agglomeration and rate of ionic dissolution. Moreover, when A549s were exposed to AgNPs in AF, the cells displayed lower cytotoxicity and stress rates, corresponding to a fluid-dependent drop in silver ion production. This work highlights the need for enhanced in vitro

  6. National Water Model: Providing the Nation with Actionable Water Intelligence

    Science.gov (United States)

    Aggett, G. R.; Bates, B.

    2017-12-01

    The National Water Model (NWM) provides national, street-level detail of water movement through time and space. Operating hourly, this flood of information offers enormous benefits in the form of water resource management, natural disaster preparedness, and the protection of life and property. The Geo-Intelligence Division at the NOAA National Water Center supplies forecasters and decision-makers with timely, actionable water intelligence through the processing of billions of NWM data points every hour. These datasets include current streamflow estimates, short and medium range streamflow forecasts, and many other ancillary datasets. The sheer amount of NWM data produced yields a dataset too large to allow for direct human comprehension. As such, it is necessary to undergo model data post-processing, filtering, and data ingestion by visualization web apps that make use of cartographic techniques to bring attention to the areas of highest urgency. This poster illustrates NWM output post-processing and cartographic visualization techniques being developed and employed by the Geo-Intelligence Division at the NOAA National Water Center to provide national actionable water intelligence.

  7. Insights into channel dysfunction from modelling and molecular dynamics simulations.

    Science.gov (United States)

    Musgaard, Maria; Paramo, Teresa; Domicevica, Laura; Andersen, Ole Juul; Biggin, Philip C

    2018-04-01

    Developments in structural biology mean that the number of different ion channel structures has increased significantly in recent years. Structures of ion channels enable us to rationalize how mutations may lead to channelopathies. However, determining the structures of ion channels is still not trivial, especially as they necessarily exist in many distinct functional states. Therefore, the use of computational modelling can provide complementary information that can refine working hypotheses of both wild type and mutant ion channels. The simplest but still powerful tool is homology modelling. Many structures are available now that can provide suitable templates for many different types of ion channels, allowing a full three-dimensional interpretation of mutational effects. These structural models, and indeed the structures themselves obtained by X-ray crystallography, and more recently cryo-electron microscopy, can be subjected to molecular dynamics simulations, either as a tool to help explore the conformational dynamics in detail or simply as a means to refine the models further. Here we review how these approaches have been used to improve our understanding of how diseases might be linked to specific mutations in ion channel proteins. This article is part of the Special Issue entitled 'Channelopathies.' Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. New insight into unstable hillslopes hydrology from hydrogeochemical modelling.

    Science.gov (United States)

    Bertrand, C.; Marc, V.; Malet, J.-P.

    2010-05-01

    and mineralogical analyses or from the literature (kinetics constants). The simulations showed that pH, sulphate and calcium concentrations in groundwater could be reproduced from reasonable assumptions. However, the observed high concentrations in magnesium and sodium were not correctly simulated by the model. Furthermore, a particular anomaly in the Na+ concentration was observed in the most active part of the landslide. Lastly, isotopic investigation showed that groundwater 3H content in this sector was significantly lower than groundwater content in the other parts of the landslide and lower than the mean rainwater content. This result showed that the mean groundwater age in the active part was probably higher than elsewhere in the landslide. All these arguments led us to conclude that groundwater was locally recharged with saline waters from areas outside the watershed, coming up through the bedrock using major discontinuities. This assumption is in agreement with the geological context. de Montety, V., V. Marc, C. Emblanch, J.-P. Malet, C. Bertrand, O. Maquaire, and T. A. Bogaard, 2007, Identifying the origin of groundwater and flow processes in complex landslides affecting black marls: insights from a hydrochemical survey.: Earth Surface Processes and Landforms, v. 32, p. 32-48. Malet, J.-P. and Maquaire, O., 2003. Black marl earthflows mobility and long-term seasonal dynamic in southeastern France. In: Picarelli, L. (Ed). Proceedings of the International Conference on Fast Slope Movements: Prediction and Prevention for Risk Mitigation. Patron Editore, Bologna: 333-340. Maquaire, O., Malet, J.-P., Remaître, A., Locat, J., Klotz, S. and Guillon, J., 2003. Instability conditions of marly hillslopes: towards landsliding or gullying? The case of the Barcelonnette Bassin, South East France. Engineering Geology, 70(1-2): 109-130. Parkhurst, D.L. and Appelo, C.A.J., 1999, User's guide to PHREEQC (version 2)--A computer program for speciation, batch-reaction, one

  9. Governance, Government, and the Search for New Provider Models

    Directory of Open Access Journals (Sweden)

    Richard B. Saltman

    2016-01-01

    Full Text Available A central problem in designing effective models of provider governance in health systems has been to ensure an appropriate balance between the concerns of public sector and/or government decision-makers, on the one hand, and of non-governmental health services actors in civil society and private life, on the other. In tax-funded European health systems up to the 1980s, the state and other public sector decision-makers played a dominant role over health service provision, typically operating hospitals through national or regional governments on a command-and-control basis. In a number of countries, however, this state role has started to change, with governments first stepping out of direct service provision and now de facto pushed to focus more on steering provider organizations rather than on direct public management. In this new approach to provider governance, the state has pulled back into a regulatory role that introduces market-like incentives and management structures, which then apply to both public and private sector providers alike. This article examines some of the main operational complexities in implementing this new governance reality/strategy, specifically from a service provision (as opposed to mostly a financing or even regulatory perspective. After briefly reviewing some of the key theoretical dilemmas, the paper presents two case studies where this new approach was put into practice: primary care in Sweden and hospitals in Spain. The article concludes that good governance today needs to reflect practical operational realities if it is to have the desired effect on health sector reform outcome.

  10. Governance, Government, and the Search for New Provider Models.

    Science.gov (United States)

    Saltman, Richard B; Duran, Antonio

    2015-11-03

    A central problem in designing effective models of provider governance in health systems has been to ensure an appropriate balance between the concerns of public sector and/or government decision-makers, on the one hand, and of non-governmental health services actors in civil society and private life, on the other. In tax-funded European health systems up to the 1980s, the state and other public sector decision-makers played a dominant role over health service provision, typically operating hospitals through national or regional governments on a command-and-control basis. In a number of countries, however, this state role has started to change, with governments first stepping out of direct service provision and now de facto pushed to focus more on steering provider organizations rather than on direct public management. In this new approach to provider governance, the state has pulled back into a regulatory role that introduces market-like incentives and management structures, which then apply to both public and private sector providers alike. This article examines some of the main operational complexities in implementing this new governance reality/strategy, specifically from a service provision (as opposed to mostly a financing or even regulatory) perspective. After briefly reviewing some of the key theoretical dilemmas, the paper presents two case studies where this new approach was put into practice: primary care in Sweden and hospitals in Spain. The article concludes that good governance today needs to reflect practical operational realities if it is to have the desired effect on health sector reform outcome. © 2016 by Kerman University of Medical Sciences.

  11. Computational models of the pulmonary circulation: Insights and the move towards clinically directed studies

    Science.gov (United States)

    Tawhai, Merryn H.; Clark, Alys R.; Burrowes, Kelly S.

    2011-01-01

    Biophysically-based computational models provide a tool for integrating and explaining experimental data, observations, and hypotheses. Computational models of the pulmonary circulation have evolved from minimal and efficient constructs that have been used to study individual mechanisms that contribute to lung perfusion, to sophisticated multi-scale and -physics structure-based models that predict integrated structure-function relationships within a heterogeneous organ. This review considers the utility of computational models in providing new insights into the function of the pulmonary circulation, and their application in clinically motivated studies. We review mathematical and computational models of the pulmonary circulation based on their application; we begin with models that seek to answer questions in basic science and physiology and progress to models that aim to have clinical application. In looking forward, we discuss the relative merits and clinical relevance of computational models: what important features are still lacking; and how these models may ultimately be applied to further increasing our understanding of the mechanisms occurring in disease of the pulmonary circulation. PMID:22034608

  12. Chromosome-level genome map provides insights into diverse defense mechanisms in the medicinal fungus Ganoderma sinense

    Science.gov (United States)

    Zhu, Yingjie; Xu, Jiang; Sun, Chao; Zhou, Shiguo; Xu, Haibin; Nelson, David R.; Qian, Jun; Song, Jingyuan; Luo, Hongmei; Xiang, Li; Li, Ying; Xu, Zhichao; Ji, Aijia; Wang, Lizhi; Lu, Shanfa; Hayward, Alice; Sun, Wei; Li, Xiwen; Schwartz, David C.; Wang, Yitao; Chen, Shilin

    2015-01-01

    Fungi have evolved powerful genomic and chemical defense systems to protect themselves against genetic destabilization and other organisms. However, the precise molecular basis involved in fungal defense remain largely unknown in Basidiomycetes. Here the complete genome sequence, as well as DNA methylation patterns and small RNA transcriptomes, was analyzed to provide a holistic overview of secondary metabolism and defense processes in the model medicinal fungus, Ganoderma sinense. We reported the 48.96 Mb genome sequence of G. sinense, consisting of 12 chromosomes and encoding 15,688 genes. More than thirty gene clusters involved in the biosynthesis of secondary metabolites, as well as a large array of genes responsible for their transport and regulation were highlighted. In addition, components of genome defense mechanisms, namely repeat-induced point mutation (RIP), DNA methylation and small RNA-mediated gene silencing, were revealed in G. sinense. Systematic bioinformatic investigation of the genome and methylome suggested that RIP and DNA methylation combinatorially maintain G. sinense genome stability by inactivating invasive genetic material and transposable elements. The elucidation of the G. sinense genome and epigenome provides an unparalleled opportunity to advance our understanding of secondary metabolism and fungal defense mechanisms. PMID:26046933

  13. Mathematical modeling provides kinetic details of the human immune response to vaccination

    Directory of Open Access Journals (Sweden)

    Dustin eLe

    2015-01-01

    Full Text Available With major advances in experimental techniques to track antigen-specific immune responses many basic questions on the kinetics of virus-specific immunity in humans remain unanswered. To gain insights into kinetics of T and B cell responses in human volunteers we combine mathematical models and experimental data from recent studies employing vaccines against yellow fever and smallpox. Yellow fever virus-specific CD8 T cell population expanded slowly with the average doubling time of 2 days peaking 2.5 weeks post immunization. Interestingly, we found that the peak of the yellow fever-specific CD8 T cell response is determined by the rate of T cell proliferation and not by the precursor frequency of antigen-specific cells as has been suggested in several studies in mice. We also found that while the frequency of virus-specific T cells increases slowly, the slow increase can still accurately explain clearance of yellow fever virus in the blood. Our additional mathematical model describes well the kinetics of virus-specific antibody-secreting cell and antibody response to vaccinia virus in vaccinated individuals suggesting that most of antibodies in 3 months post immunization are derived from the population of circulating antibody-secreting cells. Taken together, our analysis provides novel insights into mechanisms by which live vaccines induce immunity to viral infections and highlight challenges of applying methods of mathematical modeling to the current, state-of-the-art yet limited immunological data.

  14. Mathematical modeling provides kinetic details of the human immune response to vaccination.

    Science.gov (United States)

    Le, Dustin; Miller, Joseph D; Ganusov, Vitaly V

    2014-01-01

    With major advances in experimental techniques to track antigen-specific immune responses many basic questions on the kinetics of virus-specific immunity in humans remain unanswered. To gain insights into kinetics of T and B cell responses in human volunteers we combined mathematical models and experimental data from recent studies employing vaccines against yellow fever and smallpox. Yellow fever virus-specific CD8 T cell population expanded slowly with the average doubling time of 2 days peaking 2.5 weeks post immunization. Interestingly, we found that the peak of the yellow fever-specific CD8 T cell response was determined by the rate of T cell proliferation and not by the precursor frequency of antigen-specific cells as has been suggested in several studies in mice. We also found that while the frequency of virus-specific T cells increased slowly, the slow increase could still accurately explain clearance of yellow fever virus in the blood. Our additional mathematical model described well the kinetics of virus-specific antibody-secreting cell and antibody response to vaccinia virus in vaccinated individuals suggesting that most of antibodies in 3 months post immunization were derived from the population of circulating antibody-secreting cells. Taken together, our analysis provided novel insights into mechanisms by which live vaccines induce immunity to viral infections and highlighted challenges of applying methods of mathematical modeling to the current, state-of-the-art yet limited immunological data.

  15. Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

    NARCIS (Netherlands)

    Strawbridge, Rona J.; Dupuis, Josee; Prokopenko, Inga; Barker, Adam; Ahlqvist, Emma; Rybin, Denis; Petrie, John R.; Travers, Mary E.; Bouatia-Naji, Nabila; Dimas, Antigone S.; Nica, Alexandra; Wheeler, Eleanor; Chen, Han; Voight, Benjamin F.; Taneera, Jalal; Kanoni, Stavroula; Peden, John F.; Turrini, Fabiola; Gustafsson, Stefan; Zabena, Carina; Almgren, Peter; Barker, David J. P.; Barnes, Daniel; Dennison, Elaine M.; Eriksson, Johan G.; Eriksson, Per; Eury, Elodie; Folkersen, Lasse; Fox, Caroline S.; Frayling, Timothy M.; Goel, Anuj; Gu, Harvest F.; Horikoshi, Momoko; Isomaa, Bo; Jackson, Anne U.; Jameson, Karen A.; Kajantie, Eero; Kerr-Conte, Julie; Kuulasmaa, Teemu; Kuusisto, Johanna; Loos, Ruth J. F.; Luan, Jian'an; Makrilakis, Konstantinos; Manning, Alisa K.; Teresa Martinez-Larrad, Maria; Narisu, Narisu; Mannila, Maria Nastase; Ohrvik, John; Osmond, Clive; Pascoe, Laura

    2011-01-01

    OBJECTIVE-Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired beta-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about

  16. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

    NARCIS (Netherlands)

    Strawbridge, R.J.; Dupuis, J.; Prokopenko, I.; Barker, A.; Ahlqvist, E.; Rybin, D.; Petrie, J.R.; Travers, M.E.; Bouatia-Naji, N.; Dimas, A.S.; Nica, A.; Wheeler, E.; Chen, H.; Voight, B.F.; Taneera, J.; Kanoni, S.; Peden, J.F.; Turrini, F.; Gustafsson, S.; Zabena, C.; Almgren, P.; Barker, D.J.; Barnes, D.; Dennison, E.M.; Eriksson, J.G.; Eriksson, P.; Eury, E.; Folkersen, L.; Fox, C.S.; Frayling, T.M.; Goel, A.; Gu, H.F.; Horikoshi, M.; Isomaa, B.; Jackson, A.U.; Jameson, K.A.; Kajantie, E.; Kerr-Conte, J.; Kuulasmaa, T.; Kuusisto, J.; Loos, R.J.; Luan, J.; Makrilakis, K.; Manning, A.K.; Martinez-Larrad, M.T.; Narisu, N.; Nastase Mannila, M.; Ohrvik, J.; Osmond, C.; Pascoe, L.; Payne, F.; Sayer, A.A.; Sennblad, B.; Silveira, A.; Stancakova, A.; Stirrups, K.; Swift, A.J.; Syvanen, A.C.; Tuomi, T.; Hooft, F. van 't; Walker, M.; Weedon, M.N.; Xie, W.; Zethelius, B.; Ongen, H.; Malarstig, A.; Hopewell, J.C.; Saleheen, D.; Chambers, J.; Parish, S.; Danesh, J.; Kooner, J.; Ostenson, C.G.; Lind, L.; Cooper, C.C.; Serrano-Rios, M.; Ferrannini, E.; Forsen, T.J.; Clarke, R.; Franzosi, M.G.; Seedorf, U.; Watkins, H.; Froguel, P.; Johnson, P.; Deloukas, P.; Collins, F.S.; Laakso, M.; Dermitzakis, E.T.; Boehnke, M.; McCarthy, M.I.; Wareham, N.J.; Groop, L.; Pattou, F.; Gloyn, A.L.; Dedoussis, G.V.; Lyssenko, V.; Meigs, J.B.; Barroso, I.; Watanabe, R.M.; Heijer, M. den; Kiemeney, L.A.L.M.; et al.,

    2011-01-01

    OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired beta-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about

  17. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

    NARCIS (Netherlands)

    Strawbridge, Rona J.; Dupuis, Josée; Prokopenko, Inga; Barker, Adam; Ahlqvist, Emma; Rybin, Denis; Petrie, John R.; Travers, Mary E.; Bouatia-Naji, Nabila; Dimas, Antigone S.; Nica, Alexandra; Wheeler, Eleanor; Chen, Han; Voight, Benjamin F.; Taneera, Jalal; Kanoni, Stavroula; Peden, John F.; Turrini, Fabiola; Gustafsson, Stefan; Zabena, Carina; Almgren, Peter; Barker, David J. P.; Barnes, Daniel; Dennison, Elaine M.; Eriksson, Johan G.; Eriksson, Per; Eury, Elodie; Folkersen, Lasse; Fox, Caroline S.; Frayling, Timothy M.; Goel, Anuj; Gu, Harvest F.; Horikoshi, Momoko; Isomaa, Bo; Jackson, Anne U.; Jameson, Karen A.; Kajantie, Eero; Kerr-Conte, Julie; Kuulasmaa, Teemu; Kuusisto, Johanna; Loos, Ruth J. F.; Luan, Jian'an; Makrilakis, Konstantinos; Manning, Alisa K.; Martínez-Larrad, María Teresa; Narisu, Narisu; Nastase Mannila, Maria; Boekholdt, S. Matthijs; Kastelein, John J. P.; Rosendaal, Frits R.

    2011-01-01

    Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D

  18. Targeted gene panels and microbiota analysis provide insight into the effects of effects of alternative production diet formulations on channel catfish nutritional physiology

    Science.gov (United States)

    The present research evaluated targeted gene panels and microbiota analysis to provide greater insight into the effects of alternatively-sourced dietary ingredients on production indices, gut health, changes in the gut microbiota and genes involved in the regulation of appetite, growth, metabolism, ...

  19. The Asian arowana (Scleropages formosus) genome provides new insights into the evolution of an early lineage of teleosts

    DEFF Research Database (Denmark)

    Bian, Chao; Hu, Yinchang; Ravi, Vydianathan

    2016-01-01

    five Hox clusters. Differential gene expression among three varieties provides insights into the genetic basis of colour variation. A potential heterogametic sex chromosome is identified in the female arowana karyotype, suggesting that the sex is determined by a ZW/ZZ sex chromosomal system. The high...

  20. Long, paired A'A/Pahoehoe flows of Mauna Loa: Volcanological significance and insights they provide into volcano plumbing systems

    Science.gov (United States)

    Rowland, Scott K.; Walker, George P. L.

    1987-01-01

    The long lava flows of Mauna Loa, Hawaii have been cited as Earth's closed analogs to the large Martian flows. It is therefore important to understand the flow mechanics and characteristics of the Mauna Loa flows and to make use of these in an attempt to gain insights into Martian eruptive processes. Two fundamentally different kinds of long lava flows can be distinguished on Hawaiian volcanoes as in Martian flows. The two kinds may have identical initial viscosities, chemical compositions, flow lengths, and flow volumes, but their flow mechanisms and thermal energy budgets are radically different. One travels a distance set by the discharge rate as envisaged by Walker and Wadge, and the other travels a distance set mainly by the eruption duration and ground slope. In the Mauna Loa lavas, yield strength becomes an important flow morphology control only in the distal part of a'a lavas. The occurrence of paired flows on Mauna Loa yields insights into the internal plumbing systems of the volcano, and it is significant that all of the volume of the a'a flow must be stored in a magma chamber before eruption, while none of the volume of the pahoehoe needs to be so stored. Differentiation between the two kinds of flows on images of Martian volcanoes is possible and hence an improved understanding of these huge structures is acquired.

  1. Long, paired A'A/Pahoehoe flows of Mauna Loa: Volcanological significance and insights they provide into volcano plumbing systems

    International Nuclear Information System (INIS)

    Rowland, S.K.; Walker, G.P.L.

    1987-01-01

    The long lava flows of Mauna Loa, Hawaii have been cited as Earth's closed analogs to the large Martian flows. It is therefore important to understand the flow mechanics and characteristics of the Mauna Loa flows and to make use of these in an attempt to gain insights into Martian eruptive processes. Two fundamentally different kinds of long lava flows can be distinguished on Hawaiian volcanoes as in Martian flows. The two kinds may have identical initial viscosities, chemical compositions, flow lengths, and flow volumes, but their flow mechanisms and thermal energy budgets are radically different. One travels a distance set by the discharge rate as envisaged by Walker and Wadge, and the other travels a distance set mainly by the eruption duration and ground slope. In the Mauna Loa lavas, yield strength becomes an important flow morphology control only in the distal part of a'a lavas. The occurrence of paired flows on Mauna Loa yields insights into the internal plumbing systems of the volcano, and it is significant that all of the volume of the a'a flow must be stored in a magma chamber before eruption, while none of the volume of the pahoehoe needs to be so stored. Differentiation between the two kinds of flows on images of Martian volcanoes is possible and hence an improved understanding of these huge structures is acquired

  2. Comparison of the Incorporation of DHA in Circulatory and Neural Tissue When Provided as Triacylglycerol (TAG), Monoacylglycerol (MAG) or Phospholipids (PL) Provides New Insight into Fatty Acid Bioavailability.

    Science.gov (United States)

    Destaillats, Frédéric; Oliveira, Manuel; Bastic Schmid, Viktoria; Masserey-Elmelegy, Isabelle; Giuffrida, Francesca; Thakkar, Sagar K; Dupuis, Lénaïck; Gosoniu, Maria Laura; Cruz-Hernandez, Cristina

    2018-05-15

    Phospholipids (PL) or partial acylglycerols such as sn -1(3)-monoacylglycerol (MAG) are potent dietary carriers of long-chain polyunsaturated fatty acids (LC-PUFA) and have been reported to provide superior bioavailability when compared to conventional triacylglycerol (TAG). The main objective of the present study was to compare the incorporation of docosahexaenoic acid (DHA) in plasma, erythrocytes, retina and brain tissues in adult rats when provided as PL (PL-DHA) and MAG (MAG-DHA). Conventional dietary DHA oil containing TAG (TAG-DHA) as well as control chow diet were used to evaluate the potency of the two alternative DHA carriers over a 60-day feeding period. Fatty acid profiles were determined in erythrocytes and plasma lipids at time 0, 7, 14, 28, 35 and 49 days of the experimental period and in retina, cortex, hypothalamus, and hippocampus at 60 days. The assessment of the longitudinal evolution of DHA in erythrocyte and plasma lipids suggest that PL-DHA and MAG-DHA are efficient carriers of dietary DHA when compared to conventional DHA oil (TAG-DHA). Under these experimental conditions, both PL-DHA and MAG-DHA led to higher incorporations of DHA erythrocytes lipids compared to TAG-DHA group. After 60 days of supplementation, statistically significant increase in DHA level incorporated in neural tissues analyzed were observed in the DHA groups compared with the control. The mechanism explaining hypothetically the difference observed in circulatory lipids is discussed.

  3. Providing surgical care in Somalia: A model of task shifting.

    Science.gov (United States)

    Chu, Kathryn M; Ford, Nathan P; Trelles, Miguel

    2011-07-15

    Somalia is one of the most political unstable countries in the world. Ongoing insecurity has forced an inconsistent medical response by the international community, with little data collection. This paper describes the "remote" model of surgical care by Medecins Sans Frontieres, in Guri-El, Somalia. The challenges of providing the necessary prerequisites for safe surgery are discussed as well as the successes and limitations of task shifting in this resource-limited context. In January 2006, MSF opened a project in Guri-El located between Mogadishu and Galcayo. The objectives were to reduce mortality due to complications of pregnancy and childbirth and from violent and non-violent trauma. At the start of the program, expatriate surgeons and anesthesiologists established safe surgical practices and performed surgical procedures. After January 2008, expatriates were evacuated due to insecurity and surgical care has been provided by local Somalian doctors and nurses with periodic supervisory visits from expatriate staff. Between October 2006 and December 2009, 2086 operations were performed on 1602 patients. The majority (1049, 65%) were male and the median age was 22 (interquartile range, 17-30). 1460 (70%) of interventions were emergent. Trauma accounted for 76% (1585) of all surgical pathology; gunshot wounds accounted for 89% (584) of violent injuries. Operative mortality (0.5% of all surgical interventions) was not higher when Somalian staff provided care compared to when expatriate surgeons and anesthesiologists. The delivery of surgical care in any conflict-settings is difficult, but in situations where international support is limited, the challenges are more extreme. In this model, task shifting, or the provision of services by less trained cadres, was utilized and peri-operative mortality remained low demonstrating that safe surgical practices can be accomplished even without the presence of fully trained surgeon and anesthesiologists. If security improves

  4. Quantitative Phosphoproteomic Analysis Provides Insight into the Response to Short-Term Drought Stress in Ammopiptanthus mongolicus Roots

    Directory of Open Access Journals (Sweden)

    Huigai Sun

    2017-10-01

    Full Text Available Drought is one of the major abiotic stresses that negatively affects plant growth and development. Ammopiptanthus mongolicus is an ecologically important shrub in the mid-Asia desert region and used as a model for abiotic tolerance research in trees. Protein phosphorylation participates in the regulation of various biological processes, however, phosphorylation events associated with drought stress signaling and response in plants is still limited. Here, we conducted a quantitative phosphoproteomic analysis of the response of A. mongolicus roots to short-term drought stress. Data are available via the iProx database with project ID IPX0000971000. In total, 7841 phosphorylation sites were found from the 2019 identified phosphopeptides, corresponding to 1060 phosphoproteins. Drought stress results in significant changes in the abundance of 103 phosphopeptides, corresponding to 90 differentially-phosphorylated phosphoproteins (DPPs. Motif-x analysis identified two motifs, including [pSP] and [RXXpS], from these DPPs. Functional enrichment and protein-protein interaction analysis showed that the DPPs were mainly involved in signal transduction and transcriptional regulation, osmotic adjustment, stress response and defense, RNA splicing and transport, protein synthesis, folding and degradation, and epigenetic regulation. These drought-corresponsive phosphoproteins, and the related signaling and metabolic pathways probably play important roles in drought stress signaling and response in A. mongolicus roots. Our results provide new information for understanding the molecular mechanism of the abiotic stress response in plants at the posttranslational level.

  5. Characterization of Arabidopsis FPS isozymes and FPS gene expression analysis provide insight into the biosynthesis of isoprenoid precursors in seeds.

    Science.gov (United States)

    Keim, Verónica; Manzano, David; Fernández, Francisco J; Closa, Marta; Andrade, Paola; Caudepón, Daniel; Bortolotti, Cristina; Vega, M Cristina; Arró, Montserrat; Ferrer, Albert

    2012-01-01

    Arabidopsis thaliana contains two genes encoding farnesyl diphosphate (FPP) synthase (FPS), the prenyl diphoshate synthase that catalyzes the synthesis of FPP from isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). In this study, we provide evidence that the two Arabidopsis short FPS isozymes FPS1S and FPS2 localize to the cytosol. Both enzymes were expressed in E. coli, purified and biochemically characterized. Despite FPS1S and FPS2 share more than 90% amino acid sequence identity, FPS2 was found to be more efficient as a catalyst, more sensitive to the inhibitory effect of NaCl, and more resistant to thermal inactivation than FPS1S. Homology modelling for FPS1S and FPS2 and analysis of the amino acid differences between the two enzymes revealed an increase in surface polarity and a greater capacity to form surface salt bridges of FPS2 compared to FPS1S. These factors most likely account for the enhanced thermostability of FPS2. Expression analysis of FPS::GUS genes in seeds showed that FPS1 and FPS2 display complementary patterns of expression particularly at late stages of seed development, which suggests that Arabidopsis seeds have two spatially segregated sources of FPP. Functional complementation studies of the Arabidopsis fps2 knockout mutant seed phenotypes demonstrated that under normal conditions FPS1S and FPS2 are functionally interchangeable. A putative role for FPS2 in maintaining seed germination capacity under adverse environmental conditions is discussed.

  6. Characterization of Arabidopsis FPS isozymes and FPS gene expression analysis provide insight into the biosynthesis of isoprenoid precursors in seeds.

    Directory of Open Access Journals (Sweden)

    Verónica Keim

    Full Text Available Arabidopsis thaliana contains two genes encoding farnesyl diphosphate (FPP synthase (FPS, the prenyl diphoshate synthase that catalyzes the synthesis of FPP from isopentenyl diphosphate (IPP and dimethylallyl diphosphate (DMAPP. In this study, we provide evidence that the two Arabidopsis short FPS isozymes FPS1S and FPS2 localize to the cytosol. Both enzymes were expressed in E. coli, purified and biochemically characterized. Despite FPS1S and FPS2 share more than 90% amino acid sequence identity, FPS2 was found to be more efficient as a catalyst, more sensitive to the inhibitory effect of NaCl, and more resistant to thermal inactivation than FPS1S. Homology modelling for FPS1S and FPS2 and analysis of the amino acid differences between the two enzymes revealed an increase in surface polarity and a greater capacity to form surface salt bridges of FPS2 compared to FPS1S. These factors most likely account for the enhanced thermostability of FPS2. Expression analysis of FPS::GUS genes in seeds showed that FPS1 and FPS2 display complementary patterns of expression particularly at late stages of seed development, which suggests that Arabidopsis seeds have two spatially segregated sources of FPP. Functional complementation studies of the Arabidopsis fps2 knockout mutant seed phenotypes demonstrated that under normal conditions FPS1S and FPS2 are functionally interchangeable. A putative role for FPS2 in maintaining seed germination capacity under adverse environmental conditions is discussed.

  7. Insight, psychopathology, explanatory models and outcome of schizophrenia in India: a prospective 5-year cohort study

    Directory of Open Access Journals (Sweden)

    Johnson Shanthi

    2012-09-01

    Full Text Available Abstract Background The sole focus of models of insight on bio-medical perspectives to the complete exclusion of local, non-medical and cultural constructs mandates review. This study attempted to investigate the impact of insight, psychopathology, explanatory models of illness on outcome of first episode schizophrenia. Method Patients diagnosed to have DSM IV schizophrenia (n = 131 were assessed prospectively for insight, psychopathology, explanatory models of illness at baseline, 6, 12 and 60 months using standard instruments. Multiple linear and logistic regression and generalized estimating equations (GEE were employed to assess predictors of outcome. Results We could follow up 95 (72.5% patients. Sixty-five of these patients (68.4% achieved remission. There was a negative relationship between psychosis rating and insight scores. Urban residence, fluctuating course of the initial illness, and improvement in global functioning at 6 months and lower psychosis rating at 12 months were significantly related to remission at 5 years. Insight scores, number of non-medical explanatory models and individual explanatory models held during the later course of the illness were significantly associated with outcome. Analysis of longitudinal data using GEE showed that women, rural residence, insight scores and number of non-medical explanatory models of illness held were significantly associated with BPRS scores during the study period. Conclusions Insight, the disease model and the number of non-medical model positively correlated with improvement in psychosis arguing for a complex interaction between the culture, context and illness variables. These finding argue that insight and explanatory models are secondary to psychopathology, course and outcome of the illness. The awareness of mental illness is a narrative act in which people make personal sense of the many challenges they face. The course and outcome of the illness, cultural context

  8. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

    DEFF Research Database (Denmark)

    Mahajan, Anubha; Go, Min Jin; Zhang, Weihua

    2014-01-01

    To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We obs...... and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry....... observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls...

  9. Applications of the SWAT Model Special Section: Overview and Insights.

    Science.gov (United States)

    Gassman, Philip W; Sadeghi, Ali M; Srinivasan, Raghavan

    2014-01-01

    The Soil and Water Assessment Tool (SWAT) model has emerged as one of the most widely used water quality watershed- and river basin-scale models worldwide, applied extensively for a broad range of hydrologic and/or environmental problems. The international use of SWAT can be attributed to its flexibility in addressing water resource problems, extensive networking via dozens of training workshops and the several international conferences that have been held during the past decade, comprehensive online documentation and supporting software, and an open source code that can be adapted by model users for specific application needs. The catalyst for this special collection of papers was the 2011 International SWAT Conference & Workshops held in Toledo, Spain, which featured over 160 scientific presentations representing SWAT applications in 37 countries. This special collection presents 22 specific SWAT-related studies, most of which were presented at the 2011 SWAT Conference; it represents SWAT applications on five different continents, with the majority of studies being conducted in Europe and North America. The papers cover a variety of topics, including hydrologic testing at a wide range of watershed scales, transport of pollutants in northern European lowland watersheds, data input and routing method effects on sediment transport, development and testing of potential new model algorithms, and description and testing of supporting software. In this introduction to the special section, we provide a synthesis of these studies within four main categories: (i) hydrologic foundations, (ii) sediment transport and routing analyses, (iii) nutrient and pesticide transport, and (iv) scenario analyses. We conclude with a brief summary of key SWAT research and development needs. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  10. Genome-wide characterization of differentially expressed genes provides insights into regulatory network of heat stress response in radish (Raphanus sativus L.).

    Science.gov (United States)

    Wang, Ronghua; Mei, Yi; Xu, Liang; Zhu, Xianwen; Wang, Yan; Guo, Jun; Liu, Liwang

    2018-03-01

    Heat stress (HS) causes detrimental effects on plant morphology, physiology, and biochemistry that lead to drastic reduction in plant biomass production and economic yield worldwide. To date, little is known about HS-responsive genes involved in thermotolerance mechanism in radish. In this study, a total of 6600 differentially expressed genes (DEGs) from the control and Heat24 cDNA libraries of radish were isolated by high-throughput sequencing. With Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, some genes including MAPK, DREB, ERF, AP2, GST, Hsf, and Hsp were predominantly assigned in signal transductions, metabolic pathways, and biosynthesis and abiotic stress-responsive pathways. These pathways played significant roles in reducing stress-induced damages and enhancing heat tolerance in radish. Expression patterns of 24 candidate genes were validated by reverse-transcription quantitative PCR (RT-qPCR). Based mainly on the analysis of DEGs combining with the previous miRNAs analysis, the schematic model of HS-responsive regulatory network was proposed. To counter the effects of HS, a rapid response of the plasma membrane leads to the opening of specific calcium channels and cytoskeletal reorganization, after which HS-responsive genes are activated to repair damaged proteins and ultimately facilitate further enhancement of thermotolerance in radish. These results could provide fundamental insight into the regulatory network underlying heat tolerance in radish and facilitate further genetic manipulation of thermotolerance in root vegetable crops.

  11. Closed-flow column experiments—Insights into solute transport provided by a damped oscillating breakthrough behavior

    Science.gov (United States)

    Ritschel, Thomas; Totsche, Kai Uwe

    2016-03-01

    Transport studies that employ column experiments in closed-flow mode complement classical approaches by providing new characteristic features observed in the solute breakthrough and equilibrium between liquid and solid phase. Specific to the closed-flow mode is the recirculation of the effluent to the inflow via a mixing vessel. Depending on the ratio of volumes of mixing vessel and water-filled pore space, a damped oscillating solute concentration emerges in the effluent and mixing vessel. The oscillation characteristics, e.g., frequency, amplitude, and damping, allow for the investigation of solute transport in a similar fashion as known for classical open-flow column experiments. However, the closed loop conserves substances released during transport within the system. In this way, solute and porous medium can equilibrate with respect to physicochemical conditions. With this paper, the features emerging in the breakthrough curves of saturated column experiments run in closed-flow mode and methods of evaluation are illustrated under experimental boundary conditions forcing the appearance of oscillations. We demonstrate that the effective pore water volume and the pumping rate can be determined from a conservative tracer breakthrough curve uniquely. In this way, external preconditioning of the material, e.g., drying, can be avoided. A reactive breakthrough experiment revealed a significant increase in the pore water pH value as a consequence of the closed loop. These results highlight the specific impact of the closed mass balance. Furthermore, the basis for the modeling of closed-flow experiments is given by the derivation of constitutive equations and numerical implementation, validated with the presented experiments.

  12. Genomic and secondary metabolite analyses of Streptomyces sp. 2AW provide insight into the evolution of the cycloheximide pathway

    Directory of Open Access Journals (Sweden)

    Elizabeth eStulberg

    2016-05-01

    Full Text Available The dearth of new antibiotics in the face of widespread antimicrobial resistance makes developing innovative strategies for discovering new antibiotics critical for the future management of infectious disease. Understanding the genetics and evolution of antibiotic producers will help guide the discovery and bioengineering of novel antibiotics. We discovered an isolate in Alaskan boreal forest soil that had broad antimicrobial activity. We elucidated the corresponding antimicrobial natural products and sequenced the genome of this isolate, designated Streptomyces sp. 2AW. This strain illustrates the chemical virtuosity typical of the Streptomyces genus, producing cycloheximide as well as two other biosynthetically unrelated antibiotics, neutramycin and hygromycin A. Combining bioinformatic and chemical analyses, we identified the gene clusters responsible for antibiotic production. Interestingly, 2AW appears dissimilar from other cycloheximide producers in that the gene encoding the polyketide synthase resides on a separate part of the chromosome from the genes responsible for tailoring cycloheximide-specific modifications. This gene arrangement and our phylogenetic analyses of the gene products suggest that 2AW holds an evolutionarily ancestral lineage of the cycloheximide pathway. Our analyses support the hypothesis that the 2AW glutaramide gene cluster is basal to the lineage wherein cycloheximide production diverged from other glutarimide antibiotics. This study illustrates the power of combining modern biochemical and genomic analyses to gain insight into the evolution of antibiotic-producing microorganisms.

  13. Vertical microbial community variability of carbonate-based cones may provide insight into ancient conical stromatolite formation

    Science.gov (United States)

    Bradley, James; Daille, Leslie; Trivedi, Christopher; Bojanowski, Caitlin; Nunn, Heather; Stamps, Blake; Johnson, Hope; Stevenson, Bradley; Berelson, Will; Corsetti, Frank; Spear, John

    2016-04-01

    Stromatolite morphogenesis is poorly understood, and the process by which microbial mats become mineralized is a primary question in microbialite formation. Ancient conical stromatolites are primarily carbonate-based whereas the few modern analogues in hot springs are either non-mineralized or mineralized by silica. A team from the 2015 International GeoBiology Course investigated carbonate-rich microbial cones from near Little Hot Creek (LHC), Long Valley Caldera, California, to investigate how conical stromatolites might form in a hot spring carbonate system. The cones rise up from a layered microbial mat on the east side of a 45° C pool with very low flow that is super-saturated with respect to CaCO3. Cone structures are 8-30 mm in height, are rigid and do not deform when removed from the pool. Morphological characterization through environmental scanning electronic microscopy revealed that the cone structure is maintained by a matrix of intertwining microbial filaments around carbonate grains. This matrix gives rise to cone-filaments that are arranged vertically or horizontally, and provides further stability to the cone. Preliminary 16S rRNA gene analysis indicated variability of community composition between different vertical levels of the cone. The cone tip had comparatively greater abundance of filamentous cyanobacteria including Leptolingbya, Phormidium and Isosphaera and fewer heterotrophs (e.g. Chloroflexi) compared to the cone bottom. This supports the hypothesis that cone formation may depend on the differential abundance of the microbial community and their potential functional roles. Metagenomic analyses of the cones revealed potential genes related to chemotaxis and motility. Specifically, a genomic bin identified as a member of the genus Isosphaera contained an hmp chemotaxis operon implicated in gliding motility in the cyanobacterium Nostoc punctiforme. Isosphaera is a Planctomycete shown to have phototactic capabilities, and may play a role in

  14. Insights: Simple Models for Teaching Equilibrium and Le Chatelier's Principle.

    Science.gov (United States)

    Russell, Joan M.

    1988-01-01

    Presents three models that have been effective for teaching chemical equilibrium and Le Chatelier's principle: (1) the liquid transfer model, (2) the fish model, and (3) the teeter-totter model. Explains each model and its relation to Le Chatelier's principle. (MVL)

  15. When to stop drying fruit: Insights from hygrothermal modelling

    International Nuclear Information System (INIS)

    Defraeye, Thijs

    2017-01-01

    Highlights: • Partial dehydration reduces energy consumption and processing time and improves product quality. • This study gives a quantitative insight in when fruit drying should be stopped. • Decrease in dryer residence time of 2%, 24% and 70% are found for different stopping criteria. - Abstract: Stopping the drying process prior to complete dehydration reduces energy consumption and processing time but can also improve product quality. Using hygrothermal simulations, different stopping criteria are evaluated, which are based on the final water activity and residual moisture content in the fruit. Their impact on drying time and moisture redistribution kinetics inside fruit is quantified. One of the variants leads to a significant reduction in residence time in the dryer (24%), compared to full dehydration. For this variant, drying is stopped when the average moisture content in the sample reaches the value corresponding to an equilibrium water activity of 60% in the sample, as determined from the sorption isotherm. At the same time, this variant does not induce problems with fruit spoilage, as a sufficiently low water activity is reached after moisture redistribution during relaxation in the ambient environment. In addition, the relation of the drying time to the drying air temperature was quantified for all stopping criteria, as well as the impact of the humidity of the ambient environment in which the dried fruits are placed afterwards. This study gives a better quantitative insight in when fruit drying should be stopped, given specific drying conditions, without having to compromise food safety.

  16. Agent-based organizational modelling for analysis of safety culture at an air navigation service provider

    International Nuclear Information System (INIS)

    Stroeve, Sybert H.; Sharpanskykh, Alexei; Kirwan, Barry

    2011-01-01

    Assessment of safety culture is done predominantly by questionnaire-based studies, which tend to reveal attitudes on immaterial characteristics (values, beliefs, norms). There is a need for a better understanding of the implications of the material aspects of an organization (structures, processes, etc.) for safety culture and their interactions with the immaterial characteristics. This paper presents a new agent-based organizational modelling approach for integrated and systematic evaluation of material and immaterial characteristics of socio-technical organizations in safety culture analysis. It uniquely considers both the formal organization and the value- and belief-driven behaviour of individuals in the organization. Results are presented of a model for safety occurrence reporting at an air navigation service provider. Model predictions consistent with questionnaire-based results are achieved. A sensitivity analysis provides insight in organizational factors that strongly influence safety culture indicators. The modelling approach can be used in combination with attitude-focused safety culture research, towards an integrated evaluation of material and immaterial characteristics of socio-technical organizations. By using this approach an organization is able to gain a deeper understanding of causes of diverse problems and inefficiencies both in the formal organization and in the behaviour of organizational agents, and to systematically identify and evaluate improvement options.

  17. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

    OpenAIRE

    Strawbridge, Rona; Dupuis, Josée; Prokopenko, Inga; Barker, Adam; Ahlqvist, Emma; Rybin, Denis; Petrie, John; Bouatia-Naji, Nabila; Dimas, Antigone; Wheeler, Eleanor; Chen, Han; Voight, Benjamin; Taneera, Jalal; Kanoni, Stavroula; Peden, John

    2011-01-01

    textabstractOBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS - We have conducted a meta-analysis of genome-wide association tests of ;2.5 million genotyped or imputed single nucleotide polymorphisms...

  18. Using Multiple Outcomes of Sexual Behavior to Provide Insights Into Chlamydia Transmission and the Effectiveness of Prevention Interventions in Adolescents.

    Science.gov (United States)

    Enns, Eva Andrea; Kao, Szu-Yu; Kozhimannil, Katy Backes; Kahn, Judith; Farris, Jill; Kulasingam, Shalini L

    2017-10-01

    Mathematical models are important tools for assessing prevention and management strategies for sexually transmitted infections. These models are usually developed for a single infection and require calibration to observed epidemiological trends in the infection of interest. Incorporating other outcomes of sexual behavior into the model, such as pregnancy, may better inform the calibration process. We developed a mathematical model of chlamydia transmission and pregnancy in Minnesota adolescents aged 15 to 19 years. We calibrated the model to statewide rates of reported chlamydia cases alone (chlamydia calibration) and in combination with pregnancy rates (dual calibration). We evaluated the impact of calibrating to different outcomes of sexual behavior on estimated input parameter values, predicted epidemiological outcomes, and predicted impact of chlamydia prevention interventions. The two calibration scenarios produced different estimates of the probability of condom use, the probability of chlamydia transmission per sex act, the proportion of asymptomatic infections, and the screening rate among men. These differences resulted in the dual calibration scenario predicting lower prevalence and incidence of chlamydia compared with calibrating to chlamydia cases alone. When evaluating the impact of a 10% increase in condom use, the dual calibration scenario predicted fewer infections averted over 5 years compared with chlamydia calibration alone [111 (6.8%) vs 158 (8.5%)]. While pregnancy and chlamydia in adolescents are often considered separately, both are outcomes of unprotected sexual activity. Incorporating both as calibration targets in a model of chlamydia transmission resulted in different parameter estimates, potentially impacting the intervention effectiveness predicted by the model.

  19. Synchrotron imaging of dentition provides insights into the biology of Hesperornis and Ichthyornis, the "last" toothed birds

    NARCIS (Netherlands)

    Dumont, Maïtena; Tafforeau, Paul; Bertin, Thomas; Bhullar, Bhart-Anjan; Field, Daniel; Schulp, Anne; Strilisky, Brandon; Thivichon-Prince, Béatrice; Viriot, Laurent; Louchart, Antoine

    2016-01-01

    Background: The dentitions of extinct organisms can provide pivotal information regarding their phylogenetic position, as well as paleobiology, diet, development, and growth. Extant birds are edentulous (toothless), but their closest relatives among stem birds, the Cretaceous Hesperornithiformes and

  20. Model organoids provide new research opportunities for ductal pancreatic cancer

    NARCIS (Netherlands)

    Boj, Sylvia F; Hwang, Chang-Il; Baker, Lindsey A; Engle, Dannielle D; Tuveson, David A; Clevers, Hans

    We recently established organoid models from normal and neoplastic murine and human pancreas tissues. These organoids exhibit ductal- and disease stage-specific characteristics and, after orthotopic transplantation, recapitulate the full spectrum of tumor progression. Pancreatic organoid technology

  1. Statistical and RBF NN models : providing forecasts and risk assessment

    OpenAIRE

    Marček, Milan

    2009-01-01

    Forecast accuracy of economic and financial processes is a popular measure for quantifying the risk in decision making. In this paper, we develop forecasting models based on statistical (stochastic) methods, sometimes called hard computing, and on a soft method using granular computing. We consider the accuracy of forecasting models as a measure for risk evaluation. It is found that the risk estimation process based on soft methods is simplified and less critical to the question w...

  2. Genome sequence of foxtail millet (Setaria italica) provides insights into grass evolution and biofuel potential

    DEFF Research Database (Denmark)

    Zhang, Gengyun; Liu, Xin; Quan, Zhiwu

    2012-01-01

    Foxtail millet (Setaria italica), a member of the Poaceae grass family, is an important food and fodder crop in arid regions and has potential for use as a C(4) biofuel. It is a model system for other biofuel grasses, including switchgrass and pearl millet. We produced a draft genome (∼423 Mb) an...

  3. Assessment of urinary concentrations of hepcidin provides novel insight into disturbances in iron homeostasis during malarial infection

    NARCIS (Netherlands)

    Mast, de Q.; Nadjm, B.; Reyburn, H.; Kemna, E.H.J.M.; Amos, B.; Laarakkers, C.M.M.; Silalye, S.; Verhoef, H.; Sauerwein, R.W.; Swinkels, D.W.; Ven, van der A.J.A.M.

    2009-01-01

    Disturbances in iron homeostasis are frequently observed in individuals with malaria. To study the effect of malaria and its treatment on iron homeostasis and to provide a mechanistic explanation for observed alterations in iron distribution, we studied the course of the iron regulatory hormone

  4. Strengthening diabetes retinopathy services in India: Qualitative insights into providers' perspectives: The India 11-city 9-state study

    Directory of Open Access Journals (Sweden)

    Nanda Kishore Kannuri

    2016-01-01

    Full Text Available Context: There is a lack of evidence on the subjective aspects of the provider perspective regarding diabetes and its complications in India. Objectives: The study was undertaken to understand the providers' perspective on the delivery of health services for diabetes and its complications, specifically the eye complications in India. Settings and Design: Hospitals providing diabetic services in government and private sectors were selected in 11 of the largest cities in India, based on geographical distribution and size. Methods: Fifty-nine semi-structured interviews conducted with physicians providing diabetes care were analyzed all interviews were recorded, transcribed, and translated. Nvivo 10 software was used to code the transcripts. Thematic analysis was conducted to analyze the data. Results: The results are presented as key themes: “Challenges in managing diabetes patients,” “Current patient management practices,” and “Strengthening diabetic retinopathy (DR services at the health systems level.” Diabetes affects people early across the social classes. Self-management was identified as an important prerequisite in controlling diabetes and its complications. Awareness level of hospital staff on DR was low. Advances in medical technology have an important role in effective management of DR. A team approach is required to provide comprehensive diabetic care. Conclusions: Sight-threatening DR is an impending public health challenge that needs a concerted effort to tackle it. A streamlined, multi-dimensional approach where all the stakeholders cooperate is important to strengthening services dealing with DR in the existing health care setup.

  5. Insight, self-stigma and psychosocial outcomes in Schizophrenia: a structural equation modelling approach.

    Science.gov (United States)

    Lien, Y-J; Chang, H-A; Kao, Y-C; Tzeng, N-S; Lu, C-W; Loh, C-H

    2018-04-01

    Poor insight is prevalent in patients with schizophrenia and has been associated with acute illness severity, medication non-adherence and poor treatment outcomes. Paradoxically, high insight has been associated with various undesirable outcomes, including low self-esteem, depression and low subjective quality of life (QoL) in patients with schizophrenia. Despite the growing body of studies conducted in Western countries supporting the pernicious effects of improved insight in psychosis, which bases on the level of self-stigma, the effects are unclear in non-Western societies. The current study examined the role of self-stigma in the relationship between insight and psychosocial outcomes in a Chinese population. A total of 170 outpatients with schizophrenia spectrum disorders were recruited from two general university hospitals. Sociodemographic data and clinical variables were recorded and self-report scales were employed to measure self-stigma, depression, insight, self-esteem and subjective QoL. Structural equation modelling (SEM) was used to analyse the cross-sectional data. High levels of self-stigma were reported by 39% of the participants (n = 67). The influences of insight, self-stigma, self-esteem and depression on subjective QoL were confirmed by the SEM results. Our model with the closest fit to the data (χ 2 = 33.28; df = 20; p = 0.03; χ 2/df = 1.66; CFI = 0.98; TLI = 0.97; RMSEA = 0.06) demonstrated that self-stigma might fully mediate the association of insight with low self-esteem, depression and poor subjective QoL. High insight into illness contributed to self-stigma, which caused low self-esteem and depression and, consequently, low QoL. Notably, insight did not directly affect self-esteem, depression or QoL. Furthermore, the association of insight with poor psychosocial outcomes was not moderated by self-stigma. Our findings support the mediating model of insight relevant to the poor psychosocial outcomes of individuals diagnosed with

  6. Appearance traits in fish farming: progress from classical genetics to genomics, providing insight into current and potential genetic improvement

    Directory of Open Access Journals (Sweden)

    Nelson eColihueque

    2014-08-01

    Full Text Available Appearance traits in fish, those external body characteristics that influence consumer acceptance at point of sale, have come to the forefront of commercial fish farming, as culture profitability is closely linked to management of these traits. Appearance traits comprise mainly body shape and skin pigmentation. Analysis of the genetic basis of these traits in different fish reveals significant genetic variation within populations, indicating potential for their genetic improvement. Work into ascertaining the minor or major genes underlying appearance traits for commercial fish is emerging, with substantial progress in model fish in terms of identifying genes that control body shape and skin colors. In this review, we describe research progress to date, especially with regard to commercial fish, and discuss genomic findings in model fish in order to better address the genetic basis of the traits. Given that appearance traits are important in commercial fish, the genomic information related to this issue promises to accelerate the selection process in coming years.

  7. Appearance traits in fish farming: progress from classical genetics to genomics, providing insight into current and potential genetic improvement

    Science.gov (United States)

    Colihueque, Nelson; Araneda, Cristian

    2014-01-01

    Appearance traits in fish, those external body characteristics that influence consumer acceptance at point of sale, have come to the forefront of commercial fish farming, as culture profitability is closely linked to management of these traits. Appearance traits comprise mainly body shape and skin pigmentation. Analysis of the genetic basis of these traits in different fish reveals significant genetic variation within populations, indicating potential for their genetic improvement. Work into ascertaining the minor or major genes underlying appearance traits for commercial fish is emerging, with substantial progress in model fish in terms of identifying genes that control body shape and skin colors. In this review, we describe research progress to date, especially with regard to commercial fish, and discuss genomic findings in model fish in order to better address the genetic basis of the traits. Given that appearance traits are important in commercial fish, the genomic information related to this issue promises to accelerate the selection process in coming years. PMID:25140172

  8. Molecular docking simulations provide insights in the substrate binding sites and possible substrates of the ABCC6 transporter.

    Directory of Open Access Journals (Sweden)

    Mohammad Jakir Hosen

    Full Text Available The human ATP-binding cassette family C member 6 (ABCC6 gene encodes an ABC transporter protein (ABCC6, primarily expressed in liver and kidney. Mutations in the ABCC6 gene cause pseudoxanthoma elasticum (PXE, an autosomal recessive connective tissue disease characterized by ectopic mineralization of the elastic fibers. The pathophysiology underlying PXE is incompletely understood, which can at least partly be explained by the undetermined nature of the ABCC6 substrates as well as the unknown substrate recognition and binding sites. Several compounds, including anionic glutathione conjugates (N-ethylmaleimide; NEM-GS and leukotriene C4 (LTC4 were shown to be modestly transported in vitro; conversely, vitamin K3 (VK3 was demonstrated not to be transported by ABCC6. To predict the possible substrate binding pockets of the ABCC6 transporter, we generated a 3D homology model of ABCC6 in both open and closed conformation, qualified for molecular docking and virtual screening approaches. By docking 10 reported in vitro substrates in our ABCC6 3D homology models, we were able to predict the substrate binding residues of ABCC6. Further, virtual screening of 4651 metabolites from the Human Serum Metabolome Database against our open conformation model disclosed possible substrates for ABCC6, which are mostly lipid and biliary secretion compounds, some of which are found to be involved in mineralization. Docking of these possible substrates in the closed conformation model also showed high affinity. Virtual screening expands this possibility to explore more compounds that can interact with ABCC6, and may aid in understanding the mechanisms leading to PXE.

  9. Contrasting Patterns of Nucleotide Substitution Rates Provide Insight into Dynamic Evolution of Plastid and Mitochondrial Genomes of Geranium

    OpenAIRE

    Park, Seongjun; Ruhlman, Tracey A.; Weng, Mao-Lun; Hajrah, Nahid H.; Sabir, Jamal S.M.; Jansen, Robert K.

    2017-01-01

    Abstract Geraniaceae have emerged as a model system for investigating the causes and consequences of variation in plastid and mitochondrial genomes. Incredible structural variation in plastid genomes (plastomes) and highly accelerated evolutionary rates have been reported in selected lineages and functional groups of genes in both plastomes and mitochondrial genomes (mitogenomes), and these phenomena have been implicated in cytonuclear incompatibility. Previous organelle genome studies have i...

  10. Comparative transcriptome analysis of two oysters, Crassostrea gigas and Crassostrea hongkongensis provides insights into adaptation to hypo-osmotic conditions.

    Directory of Open Access Journals (Sweden)

    Xuelin Zhao

    Full Text Available Environmental salinity creates a key barrier to limit the distribution of most aquatic organisms. Adaptation to osmotic fluctuation is believed to be a factor facilitating species diversification. Adaptive evolution often involves beneficial mutations at more than one locus. Bivalves hold great interest, with numerous species living in waters, as osmoconformers, who maintain the osmotic pressure balance mostly by free amino acids. In this study, 107,076,589 reads from two groups of Crassostrea hongkongensis were produced and the assembled into 130,629 contigs. Transcripts putatively involved in stress-response, innate immunity and cell processes were identified according to Gene ontology and KEGG pathway analyses. Comparing with the transcriptome of C. gigas to characterize the diversity of transcripts between species with osmotic divergence, we identified 182,806 high-quality single nucleotide polymorphisms (SNPs for C. hongkongensis, and 196,779 SNPs for C. gigas. Comparison of 11,602 pairs of putative orthologs allowed for identification of 14 protein-coding genes that experienced strong positive selection (Ka/Ks>1. In addition, 45 genes that may show signs of moderate positive selection (1 ≥ Ka/Ks>0.5 were also identified. Based on Ks ratios and divergence time between the two species published previously, we estimated a neutral transcriptome-wide substitution mutation rate of 1.39 × 10(-9 per site per year. Several genes were differentially expressed across the control and treated groups of each species. This is the first time to sequence the transcriptome of C. hongkongensis and provide the most comprehensive transcriptomic resource available for it. The increasing amount of transcriptome data on Crassostrea provides an excellent resource for phylogenetic analysis. A large number of SNPs identified in this work are expected to provide valuable resources for future marker and genotyping assay development. The analysis of natural

  11. Fruit Flies Provide New Insights in Low-Radiation Background Biology at the INFN Underground Gran Sasso National Laboratory (LNGS).

    Science.gov (United States)

    Morciano, Patrizia; Cipressa, Francesca; Porrazzo, Antonella; Esposito, Giuseppe; Tabocchini, Maria Antonella; Cenci, Giovanni

    2018-06-04

    Deep underground laboratories (DULs) were originally created to host particle, astroparticle or nuclear physics experiments requiring a low-background environment with vastly reduced levels of cosmic-ray particle interference. More recently, the range of science projects requiring an underground experiment site has greatly expanded, thus leading to the recognition of DULs as truly multidisciplinary science sites that host important studies in several fields, including geology, geophysics, climate and environmental sciences, technology/instrumentation development and biology. So far, underground biology experiments are ongoing or planned in a few of the currently operating DULs. Among these DULs is the Gran Sasso National Laboratory (LNGS), where the majority of radiobiological data have been collected. Here we provide a summary of the current scenario of DULs around the world, as well as the specific features of the LNGS and a summary of the results we obtained so far, together with other findings collected in different underground laboratories. In particular, we focus on the recent results from our studies of Drosophila melanogaster, which provide the first evidence of the influence of the radiation environment on life span, fertility and response to genotoxic stress at the organism level. Given the increasing interest in this field and the establishment of new projects, it is possible that in the near future more DULs will serve as sites of radiobiology experiments, thus providing further relevant biological information at extremely low-dose-rate radiation. Underground experiments can be nicely complemented with above-ground studies at increasing dose rate. A systematic study performed in different exposure scenarios provides a potential opportunity to address important radiation protection questions, such as the dose/dose-rate relationship for cancer and non-cancer risk, the possible existence of dose/dose-rate threshold(s) for different biological systems and

  12. Do Lumped-Parameter Models Provide the Correct Geometrical Damping?

    DEFF Research Database (Denmark)

    Andersen, Lars

    response during excitation and the geometrical damping related to free vibrations of a hexagonal footing. The optimal order of a lumped-parameter model is determined for each degree of freedom, i.e. horizontal and vertical translation as well as torsion and rocking. In particular, the necessity of coupling...... between horizontal sliding and rocking is discussed....

  13. Molecular Signatures for the PVC Clade (Planctomycetes, Verrucomicrobia, Chlamydiae and Lentisphaerae of Bacteria Provide Insights into their Evolutionary Relationships

    Directory of Open Access Journals (Sweden)

    Radhey S. Gupta

    2012-09-01

    Full Text Available The PVC superphylum is an amalgamation of species from the phyla Planctomycetes, Verrucomicrobia and Chlamydiae, along with the Lentisphaerae, Poribacteria and two other candidate divisions. The diverse species of this superphylum lack any significant marker that differentiates them from other bacteria. Recently, genome sequences for 37 species covering all of the main PVC groups of bacteria have become available. We have used these sequences to construct a phylogenetic tree based upon concatenated sequences for 16 proteins and identify molecular signatures in protein sequences that are specific for the species from these phyla or those providing molecular links among them. Of the useful molecular markers identified in the present work, 6 conserved signature indels (CSIs in the proteins Cyt c oxidase, UvrD helicase, urease and a helicase-domain containing protein are specific for the species from the Verrucomicrobia phylum; three other CSIs in an ABC transporter protein, cobyrinic acid ac-diamide synthase and SpoVG protein are specific for the Planctomycetes species. Additionally, a 3 aa insert in the RpoB protein is uniquely present in all sequenced Chlamydiae, Verrucomicrobia and Lentisphaerae species, providing evidence for the shared ancestry of the species from these three phyla. Lastly, we have also identified a conserved protein of unknown function that is exclusively found in all sequenced species from the phyla Chlamydiae, Verrucomicrobia, Lentisphaerae and Planctomycetes suggesting a specific linkage among them. The absence of this protein in Poribacteria, which branches separately from other members of the PVC clade, indicates that it is not specifically related to the PVC clade of bacteria. The molecular markers described here in addition to clarifying the evolutionary relationships among the PVC clade of bacteria also provide novel tools for their identification and for genetic and biochemical studies on these organisms.

  14. Centralised gaming models: providing optimal gambling behaviour controls

    OpenAIRE

    Griffiths, MD; Wood, RTA

    2009-01-01

    The expansion in the gaming industry and its widening attraction points to the need for ever more verifiable means of controlling problem gambling. Various strategies have been built into casino venue operations to address this, but recently, following a new focus on social responsibility, a group of experts considered the possibilities of a centralised gaming model as a more effective control mechanism for dealing with gambling behaviours.

  15. A Flexible Collaborative Innovation Model for SOA Services Providers

    OpenAIRE

    Santanna-Filho , João ,; Rabelo , Ricardo ,; Pereira-Klen , Alexandra ,

    2015-01-01

    Part 5: Innovation Networks; International audience; Software sector plays a very relevant role in current world economy. One of its characteristics is that they are mostly composed of SMEs. SMEs have been pushed to invest in innovation to keep competitive. Service Oriented Architecture (SOA) is a recent and powerful ICT paradigm for more sustainable business models. A SOA product has many differences when compared to manufacturing sector. Besides that, SOA projects are however very complex, ...

  16. A Forced Damped Oscillation Framework for Undulatory Swimming Provides New Insights into How Propulsion Arises in Active and Passive Swimming

    Science.gov (United States)

    Bhalla, Amneet Pal Singh; Griffith, Boyce E.; Patankar, Neelesh A.

    2013-01-01

    A fundamental issue in locomotion is to understand how muscle forcing produces apparently complex deformation kinematics leading to movement of animals like undulatory swimmers. The question of whether complicated muscle forcing is required to create the observed deformation kinematics is central to the understanding of how animals control movement. In this work, a forced damped oscillation framework is applied to a chain-link model for undulatory swimming to understand how forcing leads to deformation and movement. A unified understanding of swimming, caused by muscle contractions (“active” swimming) or by forces imparted by the surrounding fluid (“passive” swimming), is obtained. We show that the forcing triggers the first few deformation modes of the body, which in turn cause the translational motion. We show that relatively simple forcing patterns can trigger seemingly complex deformation kinematics that lead to movement. For given muscle activation, the forcing frequency relative to the natural frequency of the damped oscillator is important for the emergent deformation characteristics of the body. The proposed approach also leads to a qualitative understanding of optimal deformation kinematics for fast swimming. These results, based on a chain-link model of swimming, are confirmed by fully resolved computational fluid dynamics (CFD) simulations. Prior results from the literature on the optimal value of stiffness for maximum speed are explained. PMID:23785272

  17. A forced damped oscillation framework for undulatory swimming provides new insights into how propulsion arises in active and passive swimming.

    Science.gov (United States)

    Bhalla, Amneet Pal Singh; Griffith, Boyce E; Patankar, Neelesh A

    2013-01-01

    A fundamental issue in locomotion is to understand how muscle forcing produces apparently complex deformation kinematics leading to movement of animals like undulatory swimmers. The question of whether complicated muscle forcing is required to create the observed deformation kinematics is central to the understanding of how animals control movement. In this work, a forced damped oscillation framework is applied to a chain-link model for undulatory swimming to understand how forcing leads to deformation and movement. A unified understanding of swimming, caused by muscle contractions ("active" swimming) or by forces imparted by the surrounding fluid ("passive" swimming), is obtained. We show that the forcing triggers the first few deformation modes of the body, which in turn cause the translational motion. We show that relatively simple forcing patterns can trigger seemingly complex deformation kinematics that lead to movement. For given muscle activation, the forcing frequency relative to the natural frequency of the damped oscillator is important for the emergent deformation characteristics of the body. The proposed approach also leads to a qualitative understanding of optimal deformation kinematics for fast swimming. These results, based on a chain-link model of swimming, are confirmed by fully resolved computational fluid dynamics (CFD) simulations. Prior results from the literature on the optimal value of stiffness for maximum speed are explained.

  18. A forced damped oscillation framework for undulatory swimming provides new insights into how propulsion arises in active and passive swimming.

    Directory of Open Access Journals (Sweden)

    Amneet Pal Singh Bhalla

    Full Text Available A fundamental issue in locomotion is to understand how muscle forcing produces apparently complex deformation kinematics leading to movement of animals like undulatory swimmers. The question of whether complicated muscle forcing is required to create the observed deformation kinematics is central to the understanding of how animals control movement. In this work, a forced damped oscillation framework is applied to a chain-link model for undulatory swimming to understand how forcing leads to deformation and movement. A unified understanding of swimming, caused by muscle contractions ("active" swimming or by forces imparted by the surrounding fluid ("passive" swimming, is obtained. We show that the forcing triggers the first few deformation modes of the body, which in turn cause the translational motion. We show that relatively simple forcing patterns can trigger seemingly complex deformation kinematics that lead to movement. For given muscle activation, the forcing frequency relative to the natural frequency of the damped oscillator is important for the emergent deformation characteristics of the body. The proposed approach also leads to a qualitative understanding of optimal deformation kinematics for fast swimming. These results, based on a chain-link model of swimming, are confirmed by fully resolved computational fluid dynamics (CFD simulations. Prior results from the literature on the optimal value of stiffness for maximum speed are explained.

  19. Herbarium records are reliable sources of phenological change driven by climate and provide novel insights into species' phenological cueing mechanisms.

    Science.gov (United States)

    Davis, Charles C; Willis, Charles G; Connolly, Bryan; Kelly, Courtland; Ellison, Aaron M

    2015-10-01

    Climate change has resulted in major changes in the phenology of some species but not others. Long-term field observational records provide the best assessment of these changes, but geographic and taxonomic biases limit their utility. Plant specimens in herbaria have been hypothesized to provide a wealth of additional data for studying phenological responses to climatic change. However, no study to our knowledge has comprehensively addressed whether herbarium data are accurate measures of phenological response and thus applicable to addressing such questions. We compared flowering phenology determined from field observations (years 1852-1858, 1875, 1878-1908, 2003-2006, 2011-2013) and herbarium records (1852-2013) of 20 species from New England, United States. Earliest flowering date estimated from herbarium records faithfully reflected field observations of first flowering date and substantially increased the sampling range across climatic conditions. Additionally, although most species demonstrated a response to interannual temperature variation, long-term temporal changes in phenological response were not detectable. Our findings support the use of herbarium records for understanding plant phenological responses to changes in temperature, and also importantly establish a new use of herbarium collections: inferring primary phenological cueing mechanisms of individual species (e.g., temperature, winter chilling, photoperiod). These latter data are lacking from most investigations of phenological change, but are vital for understanding differential responses of individual species to ongoing climate change. © 2015 Botanical Society of America.

  20. Genome-level comparisons provide insight into the phylogeny and metabolic diversity of species within the genus Lactococcus.

    Science.gov (United States)

    Yu, Jie; Song, Yuqin; Ren, Yan; Qing, Yanting; Liu, Wenjun; Sun, Zhihong

    2017-11-03

    The genomic diversity of different species within the genus Lactococcus and the relationships between genomic differentiation and environmental factors remain unclear. In this study, type isolates of ten Lactococcus species/subspecies were sequenced to assess their genomic characteristics, metabolic diversity, and phylogenetic relationships. The total genome sizes varied between 1.99 (Lactococcus plantarum) and 2.46 megabases (Mb; L. lactis subsp. lactis), and the G + C content ranged from 34.81 (L. lactis subsp. hordniae) to 39.67% (L. raffinolactis) with an average value of 37.02%. Analysis of genome dynamics indicated that the genus Lactococcus has an open pan-genome, while the core genome size decreased with sequential addition at the genus and species group levels. A phylogenetic dendrogram based on the concatenated amino acid sequences of 643 core genes was largely consistent with the phylogenetic tree obtained by 16S ribosomal RNA (rRNA) genes, but it provided a more robust phylogenetic resolution than the 16S rRNA gene-based analysis. Comparative genomics indicated that species in the genus Lactococcus had high degrees of diversity in genome size, gene content, and carbohydrate metabolism. This may be important for the specific adaptations that allow different Lactococcus species to survive in different environments. These results provide a quantitative basis for understanding the genomic and metabolic diversity within the genus Lactococcus, laying the foundation for future studies on taxonomy and functional genomics.

  1. Insight into model mechanisms through automatic parameter fitting: a new methodological framework for model development.

    Science.gov (United States)

    Tøndel, Kristin; Niederer, Steven A; Land, Sander; Smith, Nicolas P

    2014-05-20

    Striking a balance between the degree of model complexity and parameter identifiability, while still producing biologically feasible simulations using modelling is a major challenge in computational biology. While these two elements of model development are closely coupled, parameter fitting from measured data and analysis of model mechanisms have traditionally been performed separately and sequentially. This process produces potential mismatches between model and data complexities that can compromise the ability of computational frameworks to reveal mechanistic insights or predict new behaviour. In this study we address this issue by presenting a generic framework for combined model parameterisation, comparison of model alternatives and analysis of model mechanisms. The presented methodology is based on a combination of multivariate metamodelling (statistical approximation of the input-output relationships of deterministic models) and a systematic zooming into biologically feasible regions of the parameter space by iterative generation of new experimental designs and look-up of simulations in the proximity of the measured data. The parameter fitting pipeline includes an implicit sensitivity analysis and analysis of parameter identifiability, making it suitable for testing hypotheses for model reduction. Using this approach, under-constrained model parameters, as well as the coupling between parameters within the model are identified. The methodology is demonstrated by refitting the parameters of a published model of cardiac cellular mechanics using a combination of measured data and synthetic data from an alternative model of the same system. Using this approach, reduced models with simplified expressions for the tropomyosin/crossbridge kinetics were found by identification of model components that can be omitted without affecting the fit to the parameterising data. Our analysis revealed that model parameters could be constrained to a standard deviation of on

  2. Osteoarthritis and metabolic dysregulation: insights from a preclinical model

    NARCIS (Netherlands)

    Visser, H.M. de

    2018-01-01

    This thesis aims to identify the effect of metabolic factors, inflammatory processes and obesity in the pathophysiology of osteoarthritis (OA), using a high-fat diet and/or traumatic injury in a small animal model. The first part of this thesis describes, the rat Groove model of OA, using a one-time

  3. Genetic models of absence epilepsy: New concepts and insights

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Coenen, A.M.L.; Schwartzkroin, P.A.

    2009-01-01

    The discovery, development, and use of genetic rodent models of absence epilepsy have led to a new theory about the origin of absence seizures. A focal zone has been identified in the peri-oral region of the somatosensory cortex in WAG/Rij and GAERS – the two most commonly used models – from which

  4. Shell-Dependent Photoluminescence Studies Provide Mechanistic Insights into the Off-Grey-On Transitions of Blinking Quantum Dots.

    Science.gov (United States)

    Gao, Feng; Bajwa, Pooja; Nguyen, Anh; Heyes, Colin D

    2017-03-28

    The majority of quantum dot (QD) blinking studies have used a model of switching between two distinct fluorescence intensity levels, "on" and "off". However, a distinct intermediate intensity level has been identified in some recent reports, a so-called "grey" or "dim" state, which has brought this binary model into question. While this grey state has been proposed to result from the formation of a trion, it is still unclear under which conditions it is present in a QD. By performing shell-dependent blinking studies on CdSe QDs, we report that the populations of the grey state and the on state are strongly dependent on both the shell material and its thickness. We found that adding a ZnS shell did not result in a significant population of the grey state. Using ZnSe as the shell material resulted in a slightly higher population of the grey state, although it was still poorly resolved. However, adding a CdS shell resulted in the population of a grey state, which depended strongly on its thickness up to 5 ML. Interestingly, while the frequency of transitions to and from the grey state showed a very strong dependence on CdS shell thickness, the brightness of and the dwell time in the grey state did not. Moreover, we found that the grey state acts as an on-pathway intermediate state between on and off states, with the thickness of the shell determining the transition probability between them. We also identified two types of blinking behavior in QDs, one that showed long-lived but lower intensity on states and another that showed short-lived but brighter on states that also depended on the shell thickness. Intensity-resolved single QD fluorescence lifetime analysis was used to identify the relationship between the various exciton decay pathways and the resulting intensity levels. We used this data to propose a model in which multiple on, grey, and off states exist whose equilibrium populations vary with time that give rise to the various intensity levels of single QDs

  5. Ground based remote sensing and physiological measurements provide novel insights into canopy photosynthetic optimization in arctic shrubs

    Science.gov (United States)

    Magney, T. S.; Griffin, K. L.; Boelman, N.; Eitel, J.; Greaves, H.; Prager, C.; Logan, B.; Oliver, R.; Fortin, L.; Vierling, L. A.

    2014-12-01

    Because changes in vegetation structure and function in the Arctic are rapid and highly dynamic phenomena, efforts to understand the C balance of the tundra require repeatable, objective, and accurate remote sensing methods for estimating aboveground C pools and fluxes over large areas. A key challenge addressing the modelling of aboveground C is to utilize process-level information from fine-scale studies. Utilizing information obtained from high resolution remote sensing systems could help to better understand the C source/sink strength of the tundra, which will in part depend on changes in photosynthesis resulting from the partitioning of photosynthetic machinery within and among deciduous shrub canopies. Terrestrial LiDAR and passive hyperspectral remote sensing measurements offer an effective, repeatable, and scalable method to understand photosynthetic performance and partitioning at the canopy scale previously unexplored in arctic systems. Using a 3-D shrub canopy model derived from LiDAR, we quantified the light regime of leaves within shrub canopies to gain a better understanding of how light interception varies in response to the Arctic's complex radiation regime. This information was then coupled with pigment sampling (i.e., xanthophylls, and Chl a/b) to evaluate the optimization of foliage photosynthetic capacity within shrub canopies due to light availability. In addition, a lab experiment was performed to validate evidence of canopy level optimization via gradients of light intensity and leaf light environment. For this, hyperspectral reflectance (photochemical reflectance index (PRI)), and solar induced fluorescence (SIF)) was collected in conjunction with destructive pigment samples (xanthophylls) and chlorophyll fluorescence measurements in both sunlit and shaded canopy positions.

  6. Large scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions.

    Directory of Open Access Journals (Sweden)

    Mandy Muller

    Full Text Available Human Papillomaviruses (HPV cause widespread infections in humans, resulting in latent infections or diseases ranging from benign hyperplasia to cancers. HPV-induced pathologies result from complex interplays between viral proteins and the host proteome. Given the major public health concern due to HPV-associated cancers, most studies have focused on the early proteins expressed by HPV genotypes with high oncogenic potential (designated high-risk HPV or HR-HPV. To advance the global understanding of HPV pathogenesis, we mapped the virus/host interaction networks of the E2 regulatory protein from 12 genotypes representative of the range of HPV pathogenicity. Large-scale identification of E2-interaction partners was performed by yeast two-hybrid screenings of a HaCaT cDNA library. Based on a high-confidence scoring scheme, a subset of these partners was then validated for pair-wise interaction in mammalian cells with the whole range of the 12 E2 proteins, allowing a comparative interaction analysis. Hierarchical clustering of E2-host interaction profiles mostly recapitulated HPV phylogeny and provides clues to the involvement of E2 in HPV infection. A set of cellular proteins could thus be identified discriminating, among the mucosal HPV, E2 proteins of HR-HPV 16 or 18 from the non-oncogenic genital HPV. The study of the interaction networks revealed a preferential hijacking of highly connected cellular proteins and the targeting of several functional families. These include transcription regulation, regulation of apoptosis, RNA processing, ubiquitination and intracellular trafficking. The present work provides an overview of E2 biological functions across multiple HPV genotypes.

  7. Large scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions.

    Science.gov (United States)

    Muller, Mandy; Jacob, Yves; Jones, Louis; Weiss, Amélie; Brino, Laurent; Chantier, Thibault; Lotteau, Vincent; Favre, Michel; Demeret, Caroline

    2012-01-01

    Human Papillomaviruses (HPV) cause widespread infections in humans, resulting in latent infections or diseases ranging from benign hyperplasia to cancers. HPV-induced pathologies result from complex interplays between viral proteins and the host proteome. Given the major public health concern due to HPV-associated cancers, most studies have focused on the early proteins expressed by HPV genotypes with high oncogenic potential (designated high-risk HPV or HR-HPV). To advance the global understanding of HPV pathogenesis, we mapped the virus/host interaction networks of the E2 regulatory protein from 12 genotypes representative of the range of HPV pathogenicity. Large-scale identification of E2-interaction partners was performed by yeast two-hybrid screenings of a HaCaT cDNA library. Based on a high-confidence scoring scheme, a subset of these partners was then validated for pair-wise interaction in mammalian cells with the whole range of the 12 E2 proteins, allowing a comparative interaction analysis. Hierarchical clustering of E2-host interaction profiles mostly recapitulated HPV phylogeny and provides clues to the involvement of E2 in HPV infection. A set of cellular proteins could thus be identified discriminating, among the mucosal HPV, E2 proteins of HR-HPV 16 or 18 from the non-oncogenic genital HPV. The study of the interaction networks revealed a preferential hijacking of highly connected cellular proteins and the targeting of several functional families. These include transcription regulation, regulation of apoptosis, RNA processing, ubiquitination and intracellular trafficking. The present work provides an overview of E2 biological functions across multiple HPV genotypes.

  8. A mathematical model for carbon dioxide elimination: an insight for tuning mechanical ventilation.

    Science.gov (United States)

    Pomprapa, Anake; Schwaiberger, David; Lachmann, Burkhard; Leonhardt, Steffen

    2014-01-01

    The aim is to provide better understanding of carbon dioxide (CO2) elimination during ventilation for both the healthy and atelectatic condition, derived in a pressure-controlled mode. Therefore, we present a theoretical analysis of CO2 elimination of healthy and diseased lungs. Based on a single-compartment model, CO2 elimination is mathematically modeled and its contours were plotted as a function of temporal settings and driving pressure. The model was validated within some level of tolerance on an average of 4.9% using porcine dynamics. CO2 elimination is affected by various factors, including driving pressure, temporal variables from mechanical ventilator settings, lung mechanics and metabolic rate. During respiratory care, CO2 elimination is a key parameter for bedside monitoring, especially for patients with pulmonary disease. This parameter provides valuable insight into the status of an atelectatic lung and of cardiopulmonary pathophysiology. Therefore, control of CO2 elimination should be based on the fine tuning of the driving pressure and temporal ventilator settings. However, for critical condition of hypercapnia, airway resistance during inspiration and expiration should be additionally measured to determine the optimal percent inspiratory time (%TI) to maximize CO2 elimination for treating patients with hypercapnia.

  9. Biology and therapy of inherited retinal degenerative disease: insights from mouse models

    Science.gov (United States)

    Veleri, Shobi; Lazar, Csilla H.; Chang, Bo; Sieving, Paul A.; Banin, Eyal; Swaroop, Anand

    2015-01-01

    Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases. PMID:25650393

  10. Biology and therapy of inherited retinal degenerative disease: insights from mouse models

    Directory of Open Access Journals (Sweden)

    Shobi Veleri

    2015-02-01

    Full Text Available Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases.

  11. Transcriptional profiling provides insights into metronomic cyclophosphamide-activated, innate immune-dependent regression of brain tumor xenografts

    International Nuclear Information System (INIS)

    Doloff, Joshua C; Waxman, David J

    2015-01-01

    Cyclophosphamide treatment on a six-day repeating metronomic schedule induces a dramatic, innate immune cell-dependent regression of implanted gliomas. However, little is known about the underlying mechanisms whereby metronomic cyclophosphamide induces innate immune cell mobilization and recruitment, or about the role of DNA damage and cell stress response pathways in eliciting the immune responses linked to tumor regression. Untreated and metronomic cyclophosphamide-treated human U251 glioblastoma xenografts were analyzed on human microarrays at two treatment time points to identify responsive tumor cell-specific factors and their upstream regulators. Mouse microarray analysis across two glioma models (human U251, rat 9L) was used to identify host factors and gene networks that contribute to the observed immune and tumor regression responses. Metronomic cyclophosphamide increased expression of tumor cell-derived DNA damage, cell stress, and cell death genes, which may facilitate innate immune activation. Increased expression of many host (mouse) immune networks was also seen in both tumor models, including complement components, toll-like receptors, interferons, and cytolysis pathways. Key upstream regulators activated by metronomic cyclophosphamide include members of the interferon, toll-like receptor, inflammatory response, and PPAR signaling pathways, whose activation may contribute to anti-tumor immunity. Many upstream regulators inhibited by metronomic cyclophosphamide, including hypoxia-inducible factors and MAP kinases, have glioma-promoting activity; their inhibition may contribute to the therapeutic effectiveness of the six-day repeating metronomic cyclophosphamide schedule. Large numbers of responsive cytokines, chemokines and immune regulatory genes linked to innate immune cell recruitment and tumor regression were identified, as were several immunosuppressive factors that may contribute to the observed escape of some tumors from metronomic CPA

  12. Dissecting the chloroplast proteome of chickpea (Cicer arietinum L.) provides new insights into classical and non-classical functions.

    Science.gov (United States)

    Lande, Nilesh Vikram; Subba, Pratigya; Barua, Pragya; Gayen, Dipak; Keshava Prasad, T S; Chakraborty, Subhra; Chakraborty, Niranjan

    2017-08-08

    Chloroplast, the energy organelle unique to plant cells, is a dynamic entity which integrates an array of metabolic pathways and serves as first level for energy conversion for the entire ecological hierarchy. Increasing amount of sequence data and evolution of mass spectrometric approaches has opened up new avenues for opportune exploration of the global proteome of this organelle. In our study, we aimed at generation of a comprehensive catalogue of chloroplast proteins in a grain legume, chickpea and provided a reference proteome map. To accurately assign the identified proteins, purity of chloroplast-enriched fraction was stringently monitored by multiple chemical and immunological indexes, besides pigment and enzyme analyses. The proteome analysis led to the identification of 2451 proteins, including 27 isoforms, which include predicted and novel chloroplast constituents. The identified proteins were validated through their sequence analysis. Extensive sequence based localization prediction revealed more than 50% proteins to be chloroplast resident by at least two different algorithms. Chromosomal distribution of identified proteins across nuclear and chloroplast genome unveiled the presence of 55 chloroplast encoded gene. In depth comparison of our dataset with the non-redundant set of chloroplast proteins identified so far across other species revealed novel as well as overlapping candidates. Pulses add large amount of nitrogen to the soil and has very low water footprint and therefore, contributes to fortification of sustainable agriculture. Chickpea is one of the earliest cultivated legumes and serves as an energy and protein source for humans and animals. Chloroplasts are the unique organelles which conduct photosynthesis. Investigation on chloroplast proteome is of particular significance, especially to plant biologists, as it would allow a better understanding of chloroplast function in plants. Generation of a saturated proteome map would not only

  13. A new fossil dolphin Dilophodelphis fordycei provides insight into the evolution of supraorbital crests in Platanistoidea (Mammalia, Cetacea)

    Science.gov (United States)

    Boersma, Alexandra T.; McCurry, Matthew R.; Pyenson, Nicholas D.

    2017-05-01

    Many odontocete groups have developed enlarged facial crests, although these crests differ in topography, composition and function. The most elaborate crests occur in the South Asian river dolphin (Platanista gangetica), in which they rise dorsally as delicate, pneumatized wings anterior of the facial bones. Their position wrapping around the melon suggests their involvement in sound propagation for echolocation. To better understand the origin of crests in this lineage, we examined facial crests among fossil and living Platanistoidea, including a new taxon, Dilophodelphis fordycei, nov. gen. and sp., described herein, from the Early Miocene Astoria Formation of Oregon, USA. We measured the physical extent and thickness of platanistoid crests, categorized their relative position and used computed tomography scans to examine their internal morphology and relative bone density. Integrating these traits in a phylogenetic context, we determined that the onset of crest elaboration or enlargement and the evolution of crest pneumatization among the platanistoids were separate events, with crest enlargement beginning in the Oligocene. However, we find no evidence for pneumatization until possibly the Early Miocene, although certainly by the Middle Miocene. Such an evolutionary context, including data from the fossil record, should inform modelling efforts that seek to understand the diversity of sound generation morphology in Odontoceti.

  14. A genomic survey of positive selection in Burkholderia pseudomallei provides insights into the evolution of accidental virulence.

    Directory of Open Access Journals (Sweden)

    Tannistha Nandi

    2010-04-01

    Full Text Available Certain environmental microorganisms can cause severe human infections, even in the absence of an obvious requirement for transition through an animal host for replication ("accidental virulence". To understand this process, we compared eleven isolate genomes of Burkholderia pseudomallei (Bp, a tropical soil microbe and causative agent of the human and animal disease melioidosis. We found evidence for the existence of several new genes in the Bp reference genome, identifying 282 novel genes supported by at least two independent lines of supporting evidence (mRNA transcripts, database homologs, and presence of ribosomal binding sites and 81 novel genes supported by all three lines. Within the Bp core genome, 211 genes exhibited significant levels of positive selection (4.5%, distributed across many cellular pathways including carbohydrate and secondary metabolism. Functional experiments revealed that certain positively selected genes might enhance mammalian virulence by interacting with host cellular pathways or utilizing host nutrients. Evolutionary modifications improving Bp environmental fitness may thus have indirectly facilitated the ability of Bp to colonize and survive in mammalian hosts. These findings improve our understanding of the pathogenesis of melioidosis, and establish Bp as a model system for studying the genetics of accidental virulence.

  15. comparative transcriptomics between Synechococcus PCC 7942 and Synechocystis PCC 6803 provide insights into mechanisms of adaptation to stress.

    Energy Technology Data Exchange (ETDEWEB)

    Konstantinos, Billis [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); European Bioinformatics Inst., Hinxton, Cambridge (United Kingdom). European Molecular Biology Lab.; Aristotle Univ., Thessaloniki (Greece). Dept. of Genetics; Billini, Maria [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Max Planck Inst. for Terrestrial Microbiology, Marburg (Germany); Tripp, Harry J. [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Kyrpides, Nikos C. [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Mavrommatis, Konstantinos [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Celgene Corp, San Francisco, CA (United States)

    2014-03-21

    Background: Synechococcus sp. PCC 7942 and Synechocystis sp. PCC 6803 are model cyanobacteria from which the metabolism and adaptive responses of other cyanobacteria are inferred. Here we report the gene expression response of these two strains to a variety of nutrient and environmental stresses of varying duration, using transcriptomics. Our data comprise both stranded and 5? enriched libraries in order to elucidate many aspects of the transcriptome. Results: Both organisms were exposed to stress conditions due to nutrient deficiency (inorganic carbon) or change of environmental conditions (salinity, temperature, pH, light) sampled at 1 and 24 hours after the application of stress. The transcriptome profile of each strain revealed similarities and differences in gene expression for photosynthetic and respiratory electron transport chains and carbon fixation. Transcriptome profiles also helped us improve the structural annotation of the genome and identify possible missed genes (including anti-sense) and determine transcriptional units (operons). Finally, we predicted association of proteins of unknown function biochemical pathways by associating them to well-characterized ones based on their transcript levels correlation. Conclusions: Overall, this study results an informative annotation of those species and the comparative analysis of the response of the two organisms revealed similarities but also significant changes in the way they respond to external stress and the duration of the response

  16. The Structure of a Sugar Transporter of the Glucose EIIC Superfamily Provides Insight into the Elevator Mechanism of Membrane Transport.

    Science.gov (United States)

    McCoy, Jason G; Ren, Zhenning; Stanevich, Vitali; Lee, Jumin; Mitra, Sharmistha; Levin, Elena J; Poget, Sebastien; Quick, Matthias; Im, Wonpil; Zhou, Ming

    2016-06-07

    The phosphoenolpyruvate:carbohydrate phosphotransferase systems are found in bacteria, where they play central roles in sugar uptake and regulation of cellular uptake processes. Little is known about how the membrane-embedded components (EIICs) selectively mediate the passage of carbohydrates across the membrane. Here we report the functional characterization and 2.55-Å resolution structure of a maltose transporter, bcMalT, belonging to the glucose superfamily of EIIC transporters. bcMalT crystallized in an outward-facing occluded conformation, in contrast to the structure of another glucose superfamily EIIC, bcChbC, which crystallized in an inward-facing occluded conformation. The structures differ in the position of a structurally conserved substrate-binding domain that is suggested to play a central role in sugar transport. In addition, molecular dynamics simulations suggest a potential pathway for substrate entry from the periplasm into the bcMalT substrate-binding site. These results provide a mechanistic framework for understanding substrate recognition and translocation for the glucose superfamily EIIC transporters. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Crystal structure of the bacterial luciferase/flavin complex provides insight into the function of the beta subunit.

    Science.gov (United States)

    Campbell, Zachary T; Weichsel, Andrzej; Montfort, William R; Baldwin, Thomas O

    2009-07-07

    Bacterial luciferase from Vibrio harveyi is a heterodimer composed of a catalytic alpha subunit and a homologous but noncatalytic beta subunit. Despite decades of enzymological investigation, structural evidence defining the active center has been elusive. We report here the crystal structure of V. harveyi luciferase bound to flavin mononucleotide (FMN) at 2.3 A. The isoalloxazine ring is coordinated by an unusual cis-Ala-Ala peptide bond. The reactive sulfhydryl group of Cys106 projects toward position C-4a, the site of flavin oxygenation. This structure also provides the first data specifying the conformations of a mobile loop that is crystallographically disordered in both prior crystal structures [(1995) Biochemistry 34, 6581-6586; (1996) J. Biol. Chem. 271, 21956 21968]. This loop appears to be a boundary between solvent and the active center. Within this portion of the protein, a single contact was observed between Phe272 of the alpha subunit, not seen in the previous structures, and Tyr151 of the beta subunit. Substitutions at position 151 on the beta subunit caused reductions in activity and total quantum yield. Several of these mutants were found to have decreased affinity for reduced flavin mononucleotide (FMNH(2)). These findings partially address the long-standing question of how the beta subunit stabilizes the active conformation of the alpha subunit, thereby participating in the catalytic mechanism.

  18. Transcriptomic Profiles of Brain Provide Insights into Molecular Mechanism of Feed Conversion Efficiency in Crucian Carp (Carassius auratus)

    Science.gov (United States)

    Pang, Meixia; Luo, Weiwei; Yu, Xiaomu; Zhou, Ying; Tong, Jingou

    2018-01-01

    Feed efficiency is an economically crucial trait for cultured animals, however, progress has been scarcely made in the genetic analyses of feed conversion efficiency (FCE) in fish because of the difficulties in measurement of trait phenotypes. In the present investigation, we present the first application of RNA sequencing (RNA-Seq) combined with differentially expressed genes (DEGs) analysis for identification of functional determinants related to FCE at the gene level in an aquaculture fish, crucian carp (Carassius auratus). Brain tissues of six crucian carp with extreme FCE performances were subjected to transcriptome analysis. A total of 544,612 unigenes with a mean size of 644.38 bp were obtained from Low- and High-FCE groups, and 246 DEGs that may be involved in FCE traits were identified in these two groups. qPCR confirmed that genes previously identified as up- or down-regulated by RNA-Seq were effectively up- or down-regulated under the studied conditions. Thirteen key genes, whose functions are associated with metabolism (Dgkk, Mgst3 and Guk1b), signal transduction (Vdnccsa1b, Tgfα, Nr4a1 and Tacr2) and growth (Endog, Crebrtc2, Myh7, Myh1, Myh14 and Igfbp7) were identified according to GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) annotations. Our novel findings provide useful pathway information and candidate genes for future studies of genetic mechanisms underlying FCE in crucian carp. PMID:29538345

  19. Oxidoreductases provide a more generic response to metallic stressors (Cu and Cd) than hydrolases in soil fungi: new ecotoxicological insights.

    Science.gov (United States)

    Lebrun, Jérémie D; Demont-Caulet, Nathalie; Cheviron, Nathalie; Laval, Karine; Trinsoutrot-Gattin, Isabelle; Mougin, Christian

    2016-02-01

    The present study investigates the effect of metals on the secretion of enzymes from 12 fungal strains maintained in liquid cultures. Hydrolases (acid phosphatase, β-glucosidase, β-galactosidase, and N-acetyl-β-glucosaminidase) and ligninolytic oxidoreductases (laccase, Mn, and lignin peroxidases) activities, as well as biomass production, were measured in culture fluids from fungi exposed to Cu or Cd. Our results showed that all fungi secreted most of the selected hydrolases and that about 50% of them produced a partial oxidative system in the absence of metals. Then, exposure of fungi to metals led to the decrease in biomass production. At the enzymatic level, Cu and Cd modified the secretion profiles of soil fungi. The response of hydrolases to metals was contrasted and complex and depended on metal, enzyme, and fungal strain considered. By contrast, the metals always stimulated the activity of ligninolytic oxidoreductases in fungal strains. In some of them, oxidoreductases were specifically produced following metal exposure. Fungal oxidoreductases provide a more generic response than hydrolases, constituting thus a physiological basis for their use as biomarkers of metal exposure in soils.

  20. Comparative Proteomic Analysis of the Graft Unions in Hickory (Carya cathayensis Provides Insights into Response Mechanisms to Grafting Process

    Directory of Open Access Journals (Sweden)

    Daoliang Yan

    2017-04-01

    Full Text Available Hickory (Carya cathayensis, a tree with high nutritional and economic value, is widely cultivated in China. Grafting greatly reduces the juvenile phase length and makes the large scale cultivation of hickory possible. To reveal the response mechanisms of this species to grafting, we employed a proteomics-based approach to identify differentially expressed proteins in the graft unions during the grafting process. Our study identified 3723 proteins, of which 2518 were quantified. A total of 710 differentially expressed proteins (DEPs were quantified and these were involved in various molecular functional and biological processes. Among these DEPs, 341 were up-regulated and 369 were down-regulated at 7 days after grafting compared with the control. Four auxin-related proteins were down-regulated, which was in agreement with the transcription levels of their encoding genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG analysis showed that the ‘Flavonoid biosynthesis’ pathway and ‘starch and sucrose metabolism’ were both significantly up-regulated. Interestingly, five flavonoid biosynthesis-related proteins, a flavanone 3-hyfroxylase, a cinnamate 4-hydroxylase, a dihydroflavonol-4-reductase, a chalcone synthase, and a chalcone isomerase, were significantly up-regulated. Further experiments verified a significant increase in the total flavonoid contents in scions, which suggests that graft union formation may activate flavonoid biosynthesis to increase the content of a series of downstream secondary metabolites. This comprehensive analysis provides fundamental information on the candidate proteins and secondary metabolism pathways involved in the grafting process for hickory.

  1. Complete genome sequence analysis of the fish pathogen Flavobacterium columnare provides insights into antibiotic resistance and pathogenicity related genes.

    Science.gov (United States)

    Zhang, Yulei; Zhao, Lijuan; Chen, Wenjie; Huang, Yunmao; Yang, Ling; Sarathbabu, V; Wu, Zaohe; Li, Jun; Nie, Pin; Lin, Li

    2017-10-01

    We analyzed here the complete genome sequences of a highly virulent Flavobacterium columnare Pf1 strain isolated in our laboratory. The complete genome consists of a 3,171,081 bp circular DNA with 2784 predicted protein-coding genes. Among these, 286 genes were predicted as antibiotic resistance genes, including 32 RND-type efflux pump related genes which were associated with the export of aminoglycosides, indicating inducible aminoglycosides resistances in F. columnare. On the other hand, 328 genes were predicted as pathogenicity related genes which could be classified as virulence factors, gliding motility proteins, adhesins, and many putative secreted proteases. These genes were probably involved in the colonization, invasion and destruction of fish tissues during the infection of F. columnare. Apparently, our obtained complete genome sequences provide the basis for the explanation of the interactions between the F. columnare and the infected fish. The predicted antibiotic resistance and pathogenicity related genes will shed a new light on the development of more efficient preventional strategies against the infection of F. columnare, which is a major worldwide fish pathogen. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The structure of arabidopsis thaliana OST1 provides insights into the kinase regulation mechanism in response to osmotic stress

    KAUST Repository

    Yunta, Cristina

    2011-11-01

    SnRK [SNF1 (sucrose non-fermenting-1)-related protein kinase] 2.6 [open stomata 1 (OST1)] is well characterized at molecular and physiological levels to control stomata closure in response to water-deficit stress. OST1 is a member of a family of 10 protein kinases from Arabidopsis thaliana (SnRK2) that integrates abscisic acid (ABA)-dependent and ABA-independent signals to coordinate the cell response to osmotic stress. A subgroup of protein phosphatases type 2C binds OST1 and keeps the kinase dephosphorylated and inactive. Activation of OST1 relies on the ABA-dependent inhibition of the protein phosphatases type 2C and the subsequent self-phosphorylation of the kinase. The OST1 ABA-independent activation depends on a short sequence motif that is conserved among all the members of the SnRK2 family. However, little is known about the molecular mechanism underlying this regulation. The crystallographic structure of OST1 shows that ABA-independent regulation motif stabilizes the conformation of the kinase catalytically essential α C helix, and it provides the basis of the ABA-independent regulation mechanism for the SnRK2 family of protein kinases. © 2011 Elsevier Ltd. All rights reserved.

  3. The structure of arabidopsis thaliana OST1 provides insights into the kinase regulation mechanism in response to osmotic stress

    KAUST Repository

    Yunta, Cristina; Martí nez-Ripoll, Martí n; Zhu, Jian-Kang; Albert, Armando

    2011-01-01

    SnRK [SNF1 (sucrose non-fermenting-1)-related protein kinase] 2.6 [open stomata 1 (OST1)] is well characterized at molecular and physiological levels to control stomata closure in response to water-deficit stress. OST1 is a member of a family of 10 protein kinases from Arabidopsis thaliana (SnRK2) that integrates abscisic acid (ABA)-dependent and ABA-independent signals to coordinate the cell response to osmotic stress. A subgroup of protein phosphatases type 2C binds OST1 and keeps the kinase dephosphorylated and inactive. Activation of OST1 relies on the ABA-dependent inhibition of the protein phosphatases type 2C and the subsequent self-phosphorylation of the kinase. The OST1 ABA-independent activation depends on a short sequence motif that is conserved among all the members of the SnRK2 family. However, little is known about the molecular mechanism underlying this regulation. The crystallographic structure of OST1 shows that ABA-independent regulation motif stabilizes the conformation of the kinase catalytically essential α C helix, and it provides the basis of the ABA-independent regulation mechanism for the SnRK2 family of protein kinases. © 2011 Elsevier Ltd. All rights reserved.

  4. Tobacco and alcohol sponsorship of sporting events provide insights about how food and beverage sponsorship may affect children's health.

    Science.gov (United States)

    Kelly, Bridget; Baur, Louise A; Bauman, Adrian E; King, Lesley

    2011-08-01

    Determining children's exposure to food and beverage company sponsorship, and the effect of this exposure, is important in establishing the extent to which there may be health and societal consequences. This paper aimed to provide preliminary evidence on the scope and potential effects on children of unhealthy food and beverage sponsorship. A review of published literature and media and marketing reports was conducted to determine the types of food and beverage sponsorship campaigns that children are exposed to, and the effect of corporate sponsorship (including tobacco and alcohol) on children and adolescents. A large range of food and beverage sponsorship activities, in Australia and internationally, were identified for both school and sport settings. In particular, food and beverage companies have attempted to develop a marketing presence at all levels of professional and community sport. No information was identified measuring the effect of food and beverage company sponsorship on children and adolescents. However, empirical evidence from consumer studies relating to tobacco and alcohol sponsorship has repeatedly demonstrated that sponsorship has an impact on children's product recall and product-related attitudes and behavioural intentions. While there is no available research on the direct effect of food and beverage sponsorship, the demonstrated effects of tobacco and alcohol sponsorship on children's product awareness, preferences and consumption are likely to be applicable to food companies.

  5. Transcriptome analysis provides insights into hepatic responses to moderate heat stress in the rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Li, Yongjuan; Huang, Jinqiang; Liu, Zhe; Zhou, Yanjing; Xia, Binpeng; Wang, Yongjie; Kang, Yujun; Wang, Jianfu

    2017-07-01

    The rainbow trout is an economically important fish in the world. The limited stress tolerance of this species to high summer-like temperatures usually leads to mass mortality and great economic loss. However, there is limited information on the mechanisms underlying moderate heat responses in the liver of the rainbow trout. Here, we performed transcriptome profiling of rainbow trout liver under moderate heat stress by using the Hiseq™ 4000 sequencing platform. More than 277 million clean reads were obtained from 6 libraries and aligned against the rainbow trout genome. A total of 128 unique transcripts were differentially expressed in the liver under heat-stress and control conditions, many heat shock protein genes for thermoregulation and some novel genes involved in heat stress were identified. Nine of the differently expressed genes were further validated by qRT-PCR. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that several pathways, including those for protein metabolism, energy metabolism, and immune system, were influenced by heat stress. Moreover, an important protein-processing pathway in the endoplasmic reticulum (ER) was identified, and the key role of ER-associated degradation and function of calpain as an upstream regulator of apoptosis were confirmed under heat stress. The results of this study provide a comprehensive overview of heat stress-induced transcriptional patterns in rainbow trout liver and would be particularly useful for further studies on the molecular mechanisms underlying responses to heat stress in this species. Copyright © 2017. Published by Elsevier B.V.

  6. Time-resolved studies define the nature of toxic IAPP intermediates, providing insight for anti-amyloidosis therapeutics

    Science.gov (United States)

    Abedini, Andisheh; Plesner, Annette; Cao, Ping; Ridgway, Zachary; Zhang, Jinghua; Tu, Ling-Hsien; Middleton, Chris T; Chao, Brian; Sartori, Daniel J; Meng, Fanling; Wang, Hui; Wong, Amy G; Zanni, Martin T; Verchere, C Bruce; Raleigh, Daniel P; Schmidt, Ann Marie

    2016-01-01

    Islet amyloidosis by IAPP contributes to pancreatic β-cell death in diabetes, but the nature of toxic IAPP species remains elusive. Using concurrent time-resolved biophysical and biological measurements, we define the toxic species produced during IAPP amyloid formation and link their properties to induction of rat INS-1 β-cell and murine islet toxicity. These globally flexible, low order oligomers upregulate pro-inflammatory markers and induce reactive oxygen species. They do not bind 1-anilnonaphthalene-8-sulphonic acid and lack extensive β-sheet structure. Aromatic interactions modulate, but are not required for toxicity. Not all IAPP oligomers are toxic; toxicity depends on their partially structured conformational states. Some anti-amyloid agents paradoxically prolong cytotoxicity by prolonging the lifetime of the toxic species. The data highlight the distinguishing properties of toxic IAPP oligomers and the common features that they share with toxic species reported for other amyloidogenic polypeptides, providing information for rational drug design to treat IAPP induced β-cell death. DOI: http://dx.doi.org/10.7554/eLife.12977.001 PMID:27213520

  7. Novel Parvoviruses from Wild and Domestic Animals in Brazil Provide New Insights into Parvovirus Distribution and Diversity

    Directory of Open Access Journals (Sweden)

    William Marciel de Souza

    2018-03-01

    Full Text Available Parvoviruses (family Parvoviridae are small, single-stranded DNA viruses. Many parvoviral pathogens of medical, veterinary and ecological importance have been identified. In this study, we used high-throughput sequencing (HTS to investigate the diversity of parvoviruses infecting wild and domestic animals in Brazil. We identified 21 parvovirus sequences (including twelve nearly complete genomes and nine partial genomes in samples derived from rodents, bats, opossums, birds and cattle in Pernambuco, São Paulo, Paraná and Rio Grande do Sul states. These sequences were investigated using phylogenetic and distance-based approaches and were thereby classified into eight parvovirus species (six of which have not been described previously, representing six distinct genera in the subfamily Parvovirinae. Our findings extend the known biogeographic range of previously characterized parvovirus species and the known host range of three parvovirus genera (Dependovirus, Aveparvovirus and Tetraparvovirus. Moreover, our investigation provides a window into the ecological dynamics of parvovirus infections in vertebrates, revealing that many parvovirus genera contain well-defined sub-lineages that circulate widely throughout the world within particular taxonomic groups of hosts.

  8. Transcriptomic Profiles of Brain Provide Insights into Molecular Mechanism of Feed Conversion Efficiency in Crucian Carp (Carassius auratus

    Directory of Open Access Journals (Sweden)

    Meixia Pang

    2018-03-01

    Full Text Available Feed efficiency is an economically crucial trait for cultured animals, however, progress has been scarcely made in the genetic analyses of feed conversion efficiency (FCE in fish because of the difficulties in measurement of trait phenotypes. In the present investigation, we present the first application of RNA sequencing (RNA-Seq combined with differentially expressed genes (DEGs analysis for identification of functional determinants related to FCE at the gene level in an aquaculture fish, crucian carp (Carassius auratus. Brain tissues of six crucian carp with extreme FCE performances were subjected to transcriptome analysis. A total of 544,612 unigenes with a mean size of 644.38 bp were obtained from Low- and High-FCE groups, and 246 DEGs that may be involved in FCE traits were identified in these two groups. qPCR confirmed that genes previously identified as up- or down-regulated by RNA-Seq were effectively up- or down-regulated under the studied conditions. Thirteen key genes, whose functions are associated with metabolism (Dgkk, Mgst3 and Guk1b, signal transduction (Vdnccsa1b, Tgfα, Nr4a1 and Tacr2 and growth (Endog, Crebrtc2, Myh7, Myh1, Myh14 and Igfbp7 were identified according to GO (Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes annotations. Our novel findings provide useful pathway information and candidate genes for future studies of genetic mechanisms underlying FCE in crucian carp.

  9. Evaluating a nurse-led model for providing neonatal care.

    Science.gov (United States)

    2004-07-01

    The paper presents an overview of a multi-dimensional, prospective, comparative 5-year audit of the quality of the neonatal care provided by a maternity unit in the UK delivering 2000 babies a year, where all neonatal care after 1995 was provided by advanced neonatal nurse practitioners, in relation to that provided by a range of other medically staffed comparator units. The audit includes 11 separate comparative studies supervised by a panel of independent external advisors. Data on intrapartum and neonatal mortality is reported. A review of resuscitation at birth, and a two-tier confidential inquiry into sentinel events in six units were carried out. The reliability of the routine predischarge neonatal examination was studied and, in particular, the recognition of congenital heart disease. A review of the quality of postdischarge letters was undertaken alongside an interview survey to elicit parental views on care provision. An audit of all hospital readmissions within 28 days of birth is reported. Other areas of study include management of staff stress, perceived adequacy of the training of nurse practitioners coming into post, and an assessment of unit costs. Intrapartum and neonatal death among women with a singleton pregnancy originally booked for delivery in Ashington fell 39% between 1991-1995 and 1996-2000 (5.12 vs. 3.11 deaths per 1000 births); the decline for the whole region was 27% (4.10 vs. 2.99). By all other indicators the quality of care in the nurse-managed unit was as good as, or better than, that in the medically staffed comparator units. An appropriately trained, stable team with a store of experience can deliver cot-side care of a higher quality than staff rostered to this task for a few months to gain experience, and this is probably more important than their medical or nursing background. Factors limiting the on-site availability of medical staff with paediatric expertise do not need to dictate the future disposition of maternity services.

  10. Do Cochrane reviews provide a good model for social science?

    DEFF Research Database (Denmark)

    Konnerup, Merete; Kongsted, Hans Christian

    2012-01-01

    Formalised research synthesis to underpin evidence-based policy and practice has become increasingly important in areas of public policy. In this paper we discuss whether the Cochrane standard for systematic reviews of healthcare interventions is appropriate for social research. We examine...... the formal criteria of the Cochrane Collaboration for including particular study designs and search the Cochrane Library to provide quantitative evidence on the de facto standard of actual Cochrane reviews. By identifying the sample of Cochrane reviews that consider observational designs, we are able...... to conclude that the majority of reviews appears limited to considering randomised controlled trials only. Because recent studies have delineated conditions for observational studies in social research to produce valid evidence, we argue that an inclusive approach is essential for truly evidence-based policy...

  11. Contrasting Patterns of Nucleotide Substitution Rates Provide Insight into Dynamic Evolution of Plastid and Mitochondrial Genomes of Geranium.

    Science.gov (United States)

    Park, Seongjun; Ruhlman, Tracey A; Weng, Mao-Lun; Hajrah, Nahid H; Sabir, Jamal S M; Jansen, Robert K

    2017-06-01

    Geraniaceae have emerged as a model system for investigating the causes and consequences of variation in plastid and mitochondrial genomes. Incredible structural variation in plastid genomes (plastomes) and highly accelerated evolutionary rates have been reported in selected lineages and functional groups of genes in both plastomes and mitochondrial genomes (mitogenomes), and these phenomena have been implicated in cytonuclear incompatibility. Previous organelle genome studies have included limited sampling of Geranium, the largest genus in the family with over 400 species. This study reports on rates and patterns of nucleotide substitutions in plastomes and mitogenomes of 17 species of Geranium and representatives of other Geraniaceae. As detected across other angiosperms, substitution rates in the plastome are 3.5 times higher than the mitogenome in most Geranium. However, in the branch leading to Geranium brycei/Geranium incanum mitochondrial genes experienced significantly higher dN and dS than plastid genes, a pattern that has only been detected in one other angiosperm. Furthermore, rate accelerations differ in the two organelle genomes with plastomes having increased dN and mitogenomes with increased dS. In the Geranium phaeum/Geranium reflexum clade, duplicate copies of clpP and rpoA genes that experienced asymmetric rate divergence were detected in the single copy region of the plastome. In the case of rpoA, the branch leading to G. phaeum/G. reflexum experienced positive selection or relaxation of purifying selection. Finally, the evolution of acetyl-CoA carboxylase is unusual in Geraniaceae because it is only the second angiosperm family where both prokaryotic and eukaryotic ACCases functionally coexist in the plastid. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  12. Little White Lies: Pericarp Color Provides Insights into the Origins and Evolution of Southeast Asian Weedy Rice

    Science.gov (United States)

    Cui, Yongxia; Song, Beng Kah; Li, Lin-Feng; Li, Ya-Ling; Huang, Zhongyun; Caicedo, Ana L.; Jia, Yulin; Olsen, Kenneth M.

    2016-01-01

    Weedy rice is a conspecific form of cultivated rice (Oryza sativa L.) that infests rice fields and results in severe crop losses. Weed strains in different world regions appear to have originated multiple times from different domesticated and/or wild rice progenitors. In the case of Malaysian weedy rice, a multiple-origin model has been proposed based on neutral markers and analyses of domestication genes for hull color and seed shattering. Here, we examined variation in pericarp (bran) color and its molecular basis to address how this trait evolved in Malaysian weeds and its possible role in weed adaptation. Functional alleles of the Rc gene confer proanthocyanidin pigmentation of the pericarp, a trait found in most wild and weedy Oryzas and associated with seed dormancy; nonfunctional rc alleles were strongly favored during rice domestication, and most cultivated varieties have nonpigmented pericarps. Phenotypic characterizations of 52 Malaysian weeds revealed that most strains are characterized by the pigmented pericarp; however, some weeds have white pericarps, suggesting close relationships to cultivated rice. Phylogenetic analyses indicate that the Rc haplotypes present in Malaysian weeds likely have at least three distinct origins: wild O. rufipogon, white-pericarp cultivated rice, and red-pericarp cultivated rice. These diverse origins contribute to high Rc nucleotide diversity in the Malaysian weeds. Comparison of Rc allelic distributions with other rice domestication genes suggests that functional Rc alleles may confer particular fitness benefits in weedy rice populations, for example, by conferring seed dormancy. This may promote functional Rc introgression from local wild Oryza populations. PMID:27729434

  13. Mt-rps3 is an ancient gene which provides insight into the evolution of fungal mitochondrial genomes.

    Science.gov (United States)

    Korovesi, Artemis G; Ntertilis, Maria; Kouvelis, Vassili N

    2018-05-12

    The nuclear ribosomal protein S3 (Rps3) is implicated in the assembly of the ribosomal small subunit. Fungi and plants present a gene copy in their mitochondrial (mt) genomes. An analysis of 303 complete fungal mt genomes showed that, when rps3 is found, it is either a free-standing gene or an anchored gene within the omega intron of the rnl gene. Early divergent fungi, Basidiomycota and all yeasts but the CTG group belong to the first case, and Pezizomycotina to the second. Its position, size and genetic code employed are conserved within species of the same Order. Size variability is attributed to different number of repeats. These repeats consist of AT-rich sequences. MtRps3 proteins lack the KH domain, necessary for binding to rRNA, in their N-terminal region. Their C-terminal region is conserved in all Domains of life. Phylogenetic analysis showed that nuclear and mt Rps3 proteins are descendants of archaeal and a-proteobacterial homologues, respectively. Thus, fungal mt-rps3 gene is an ancient gene which evolved within the endosymbiotic model and presents different evolutionary routes: (a) coming from a-proteobacteria, it was relocated to another region of the mt genome, (b) via its insertion to the omega intron, it was transferred to the nucleus and/or got lost, and (c) it was re-routed to the mt genome again. Today, Basidiomycota and Saccharomycetales seem to follow the first evolutionary route and almost all Pezizomycotina support the second scenario with their exceptions being the result of the third scenario, i.e., the gene's re-entry to the mt genome. Copyright © 2018. Published by Elsevier Inc.

  14. A Chromosome-Scale Assembly of the Bactrocera cucurbitae Genome Provides Insight to the Genetic Basis of white pupae

    Directory of Open Access Journals (Sweden)

    Sheina B. Sim

    2017-06-01

    Full Text Available Genetic sexing strains (GSS used in sterile insect technique (SIT programs are textbook examples of how classical Mendelian genetics can be directly implemented in the management of agricultural insect pests. Although the foundation of traditionally developed GSS are single locus, autosomal recessive traits, their genetic basis are largely unknown. With the advent of modern genomic techniques, the genetic basis of sexing traits in GSS can now be further investigated. This study is the first of its kind to integrate traditional genetic techniques with emerging genomics to characterize a GSS using the tephritid fruit fly pest Bactrocera cucurbitae as a model. These techniques include whole-genome sequencing, the development of a mapping population and linkage map, and quantitative trait analysis. The experiment designed to map the genetic sexing trait in B. cucurbitae, white pupae (wp, also enabled the generation of a chromosome-scale genome assembly by integrating the linkage map with the assembly. Quantitative trait loci analysis revealed SNP loci near position 42 MB on chromosome 3 to be tightly linked to wp. Gene annotation and synteny analysis show a near perfect relationship between chromosomes in B. cucurbitae and Muller elements A–E in Drosophila melanogaster. This chromosome-scale genome assembly is complete, has high contiguity, was generated using a minimal input DNA, and will be used to further characterize the genetic mechanisms underlying wp. Knowledge of the genetic basis of genetic sexing traits can be used to improve SIT in this species and expand it to other economically important Diptera.

  15. Germ warfare in a microbial mat community: CRISPRs provide insights into the co-evolution of host and viral genomes.

    Directory of Open Access Journals (Sweden)

    John F Heidelberg

    Full Text Available CRISPR arrays and associated cas genes are widespread in bacteria and archaea and confer acquired resistance to viruses. To examine viral immunity in the context of naturally evolving microbial populations we analyzed genomic data from two thermophilic Synechococcus isolates (Syn OS-A and Syn OS-B' as well as a prokaryotic metagenome and viral metagenome derived from microbial mats in hotsprings at Yellowstone National Park. Two distinct CRISPR types, distinguished by the repeat sequence, are found in both the Syn OS-A and Syn OS-B' genomes. The genome of Syn OS-A contains a third CRISPR type with a distinct repeat sequence, which is not found in Syn OS-B', but appears to be shared with other microorganisms that inhabit the mat. The CRISPR repeats identified in the microbial metagenome are highly conserved, while the spacer sequences (hereafter referred to as "viritopes" to emphasize their critical role in viral immunity were mostly unique and had no high identity matches when searched against GenBank. Searching the viritopes against the viral metagenome, however, yielded several matches with high similarity some of which were within a gene identified as a likely viral lysozyme/lysin protein. Analysis of viral metagenome sequences corresponding to this lysozyme/lysin protein revealed several mutations all of which translate into silent or conservative mutations which are unlikely to affect protein function, but may help the virus evade the host CRISPR resistance mechanism. These results demonstrate the varied challenges presented by a natural virus population, and support the notion that the CRISPR/viritope system must be able to adapt quickly to provide host immunity. The ability of metagenomics to track population-level variation in viritope sequences allows for a culture-independent method for evaluating the fast co-evolution of host and viral genomes and its consequence on the structuring of complex microbial communities.

  16. Sixteen kiwi (Apteryx spp) transcriptomes provide a wealth of genetic markers and insight into sex chromosome evolution in birds.

    Science.gov (United States)

    Ramstad, Kristina M; Miller, Hilary C; Kolle, Gabriel

    2016-05-26

    here will provide a rich resource for polymorphic marker development and studies of adaptation of these highly unusual and endangered birds.

  17. Transcriptome changes in Eriocheir sinensis megalopae after desalination provide insights into osmoregulation and stress adaption in larvae.

    Directory of Open Access Journals (Sweden)

    Min Hui

    Full Text Available Eriocheir sinensis, an extremely invasive alien crab species, has important economic value in China. It encounters different salinities during its life cycle, and at the megalopal stage it faces a turning point regarding the salinity in its environment. We applied RNA sequencing to E. sinensis megalopae before (MB and after (MA desalination, resulting in the discovery of 21,042 unigenes and 908 differentially expressed genes (DEGs, 4.32% of the unigenes. The DEGs primarily belonged to the Gene Ontology groups "Energy metabolism," "Oxidoreductase activity," "Translation," "Transport," "Metabolism," and "Stress response." In total, 33 DEGs related to transport processes were found, including 12 proton pump genes, three ATP-binding cassettes (ABCs, 13 solute carrier (SLC family members, two sweet sugar transporter (ST family members and three other substance transporters. Mitochondrial genes as well as genes involved in the tricarboxylic acid cycle, glycolytic pathway, or β-oxidation pathway, which can generate energy in the form of ATP, were typically up-regulated in MA. 11 unigenes related to amino acid metabolism and a large number of genes related to protein synthesis were differentially expressed in MB and MA, indicating that E. sinensis possibly adjusts its concentration of free amino acid osmolytes for hyper-osmoregulation. Additionally, 33 salinity and oxidative stress induced genes were found to be differentially expressed, such as the LEA2, HSPs, GST and coagulation factor genes. Notably, LEA2 is an extremely hydrophilic protein that responds to desiccation and reported for the first time in crabs. Therefore, we suppose that when the environment is hypo-osmotic, the megalopae might compensate for ion loss via hyper-osmoregulation by consuming more energy, accompanied by a series of stress induced adaptions. This study provides the first genome-wide transcriptome analysis of E. sinensis megalopae for studying its osmoregulation and stress

  18. Venom-related transcripts from Bothrops jararaca tissues provide novel molecular insights into the production and evolution of snake venom.

    Science.gov (United States)

    Junqueira-de-Azevedo, Inácio L M; Bastos, Carolina Mancini Val; Ho, Paulo Lee; Luna, Milene Schmidt; Yamanouye, Norma; Casewell, Nicholas R

    2015-03-01

    Attempts to reconstruct the evolutionary history of snake toxins in the context of their co-option to the venom gland rarely account for nonvenom snake genes that are paralogous to toxins, and which therefore represent important connectors to ancestral genes. In order to reevaluate this process, we conducted a comparative transcriptomic survey on body tissues from a venomous snake. A nonredundant set of 33,000 unigenes (assembled transcripts of reference genes) was independently assembled from six organs of the medically important viperid snake Bothrops jararaca, providing a reference list of 82 full-length toxins from the venom gland and specific products from other tissues, such as pancreatic digestive enzymes. Unigenes were then screened for nontoxin transcripts paralogous to toxins revealing 1) low level coexpression of approximately 20% of toxin genes (e.g., bradykinin-potentiating peptide, C-type lectin, snake venom metalloproteinase, snake venom nerve growth factor) in body tissues, 2) the identity of the closest paralogs to toxin genes in eight classes of toxins, 3) the location and level of paralog expression, indicating that, in general, co-expression occurs in a higher number of tissues and at lower levels than observed for toxin genes, and 4) strong evidence of a toxin gene reverting back to selective expression in a body tissue. In addition, our differential gene expression analyses identify specific cellular processes that make the venom gland a highly specialized secretory tissue. Our results demonstrate that the evolution and production of venom in snakes is a complex process that can only be understood in the context of comparative data from other snake tissues, including the identification of genes paralogous to venom toxins. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. 40,000-Year-Old Individual from Asia Provides Insight into Early Population Structure in Eurasia.

    Science.gov (United States)

    Yang, Melinda A; Gao, Xing; Theunert, Christoph; Tong, Haowen; Aximu-Petri, Ayinuer; Nickel, Birgit; Slatkin, Montgomery; Meyer, Matthias; Pääbo, Svante; Kelso, Janet; Fu, Qiaomei

    2017-10-23

    By at least 45,000 years before present, anatomically modern humans had spread across Eurasia [1-3], but it is not well known how diverse these early populations were and whether they contributed substantially to later people or represent early modern human expansions into Eurasia that left no surviving descendants today. Analyses of genome-wide data from several ancient individuals from Western Eurasia and Siberia have shown that some of these individuals have relationships to present-day Europeans [4, 5] while others did not contribute to present-day Eurasian populations [3, 6]. As contributions from Upper Paleolithic populations in Eastern Eurasia to present-day humans and their relationship to other early Eurasians is not clear, we generated genome-wide data from a 40,000-year-old individual from Tianyuan Cave, China, [1, 7] to study his relationship to ancient and present-day humans. We find that he is more related to present-day and ancient Asians than he is to Europeans, but he shares more alleles with a 35,000-year-old European individual than he shares with other ancient Europeans, indicating that the separation between early Europeans and early Asians was not a single population split. We also find that the Tianyuan individual shares more alleles with some Native American groups in South America than with Native Americans elsewhere, providing further support for population substructure in Asia [8] and suggesting that this persisted from 40,000 years ago until the colonization of the Americas. Our study of the Tianyuan individual highlights the complex migration and subdivision of early human populations in Eurasia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Genomic analysis of the Kiwifruit pathogen Pseudomonas syringae pv. actinidiae provides insight into the origins of an emergent plant disease.

    Directory of Open Access Journals (Sweden)

    Honour C McCann

    Full Text Available The origins of crop diseases are linked to domestication of plants. Most crops were domesticated centuries--even millennia--ago, thus limiting opportunity to understand the concomitant emergence of disease. Kiwifruit (Actinidia spp. is an exception: domestication began in the 1930s with outbreaks of canker disease caused by P. syringae pv. actinidiae (Psa first recorded in the 1980s. Based on SNP analyses of two circularized and 34 draft genomes, we show that Psa is comprised of distinct clades exhibiting negligible within-clade diversity, consistent with disease arising by independent samplings from a source population. Three clades correspond to their geographical source of isolation; a fourth, encompassing the Psa-V lineage responsible for the 2008 outbreak, is now globally distributed. Psa has an overall clonal population structure, however, genomes carry a marked signature of within-pathovar recombination. SNP analysis of Psa-V reveals hundreds of polymorphisms; however, most reside within PPHGI-1-like conjugative elements whose evolution is unlinked to the core genome. Removal of SNPs due to recombination yields an uninformative (star-like phylogeny consistent with diversification of Psa-V from a single clone within the last ten years. Growth assays provide evidence of cultivar specificity, with rapid systemic movement of Psa-V in Actinidia chinensis. Genomic comparisons show a dynamic genome with evidence of positive selection on type III effectors and other candidate virulence genes. Each clade has highly varied complements of accessory genes encoding effectors and toxins with evidence of gain and loss via multiple genetic routes. Genes with orthologs in vascular pathogens were found exclusively within Psa-V. Our analyses capture a pathogen in the early stages of emergence from a predicted source population associated with wild Actinidia species. In addition to candidate genes as targets for resistance breeding programs, our findings

  1. A transcriptomic analysis of bermudagrass (Cynodon dactylon) provides novel insights into the basis of low temperature tolerance.

    Science.gov (United States)

    Chen, Liang; Fan, Jibiao; Hu, Longxing; Hu, Zhengrong; Xie, Yan; Zhang, Yingzi; Lou, Yanhong; Nevo, Eviatar; Fu, Jinmin

    2015-09-11

    Cold stress is regarded as a key factor limiting widespread use for bermudagrass (Cynodon dactylon). Therefore, to improve cold tolerance for bermudagrass, it is urgent to understand molecular mechanisms of bermudagrass response to cold stress. However, our knowledge about the molecular responses of this species to cold stress is largely unknown. The objective of this study was to characterize the transcriptomic response to low temperature in bermudagrass by using RNA-Seq platform. Ten cDNA libraries were generated from RNA samples of leaves from five different treatments in the cold-resistant (R) and the cold-sensitive (S) genotypes, including 4 °C cold acclimation (CA) for 24 h and 48 h, freezing (-5 °C) treatments for 4 h with or without prior CA, and controls. When subjected to cold acclimation, global gene expressions were initiated more quickly in the R genotype than those in the S genotype. The R genotype activated gene expression more effectively in response to freezing temperature after 48 h CA than the S genotype. The differentially expressed genes were identified as low temperature sensing and signaling-related genes, functional proteins and transcription factors, many of which were specifically or predominantly expressed in the R genotype under cold treatments, implying that these genes play important roles in the enhanced cold hardiness of bermudagrass. KEGG pathway enrichment analysis for DEGs revealed that photosynthesis, nitrogen metabolism and carbon fixation pathways play key roles in bermudagrass response to cold stress. The results of this study may contribute to our understanding the molecular mechanism underlying the responses of bermudagrass to cold stress, and also provide important clues for further study and in-depth characterization of cold-resistance breeding candidate genes in bermudagrass.

  2. A mollusk VDR/PXR/CAR-like (NR1J) nuclear receptor provides insight into ancient detoxification mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Cruzeiro, Catarina, E-mail: catarinarcruzeiro@hotmail.com [ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto (Portugal); CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Lopes-Marques, Mónica, E-mail: monicaslm@hotmail.com [ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto (Portugal); CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Ruivo, Raquel, E-mail: ruivo.raquel@gmail.com [CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Rodrigues-Oliveira, Nádia, E-mail: nadia.oliveira@ciimar.up.pt [CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Santos, Miguel M., E-mail: santos@ciimar.up.pt [CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); FCUP - Faculty of Sciences, Department of Biology, U. Porto (Portugal); Rocha, Maria João, E-mail: mjsrocha@netcabo.pt [ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto (Portugal); CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Rocha, Eduardo, E-mail: erocha@icbas.up.pt [ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto (Portugal); CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Castro, L. Filipe C., E-mail: filipe.castro@ciimar.up.pt [CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); FCUP - Faculty of Sciences, Department of Biology, U. Porto (Portugal)

    2016-05-15

    Highlights: • A nuclear receptor orthologue of the NR1J group is isolated from a mollusc. • The molluscan NR1J transactivates gene expression upon exposure to okadaic acid but not a pesticide, esfenvarelate and triclosan. • Lineage specific gene duplications and gene loss have occurred in the NR1J of protostomes with likely impacts on detoxification mechanisms. - Abstract: The origin and diversification of the metazoan endocrine systems represents a fundamental research issue in biology. Nuclear receptors are critical components of these systems. A particular group named VDR/PXR/CAR (NR1I/J) is central in the mediation of detoxification responses. While orthologues have been thoroughly characterized in vertebrates, a sparse representation is currently available for invertebrates. Here, we provide the first isolation and characterization of a lophotrochozoan protostome VDR/PXR/CAR nuclear receptor (NR1J), in the estuarine bivalve the peppery furrow shell (Scrobicularia plana). Using a reporter gene assay, we evaluated the xenobiotic receptor plasticity comparing the human PXR with the S. plana NR1Jβ. Our results show that the molluscan receptor responds to a natural toxin (okadaic acid) in a similar fashion to that reported for other invertebrates. In contrast, the pesticide esfenvalerate displayed a unique response, since it down regulated transactivation at higher concentrations, while for triclosan no response was observed. Additionally, we uncovered lineage specific gene duplications and gene loss in the gene group encoding NRs in protostomes with likely impacts on the complexity of detoxification mechanisms across different phyla. Our findings pave the way for the development of multi-specific sensor tools to screen xenobiotic compounds acting via the NR1I/J group.

  3. Structure of the extracellular portion of CD46 provides insights into its interactions with complement proteins and pathogens.

    Directory of Open Access Journals (Sweden)

    B David Persson

    2010-09-01

    Full Text Available The human membrane cofactor protein (MCP, CD46 is a central component of the innate immune system. CD46 protects autologous cells from complement attack by binding to complement proteins C3b and C4b and serving as a cofactor for their cleavage. Recent data show that CD46 also plays a role in mediating acquired immune responses, and in triggering autophagy. In addition to these physiologic functions, a significant number of pathogens, including select adenoviruses, measles virus, human herpes virus 6 (HHV-6, Streptococci, and Neisseria, use CD46 as a cell attachment receptor. We have determined the crystal structure of the extracellular region of CD46 in complex with the human adenovirus type 11 fiber knob. Extracellular CD46 comprises four short consensus repeats (SCR1-SCR4 that form an elongated structure resembling a hockey stick, with a long shaft and a short blade. Domains SCR1, SCR2 and SCR3 are arranged in a nearly linear fashion. Unexpectedly, however, the structure reveals a profound bend between domains SCR3 and SCR4, which has implications for the interactions with ligands as well as the orientation of the protein at the cell surface. This bend can be attributed to an insertion of five hydrophobic residues in a SCR3 surface loop. Residues in this loop have been implicated in interactions with complement, indicating that the bend participates in binding to C3b and C4b. The structure provides an accurate framework for mapping all known ligand binding sites onto the surface of CD46, thereby advancing an understanding of how CD46 acts as a receptor for pathogens and physiologic ligands of the immune system.

  4. A mollusk VDR/PXR/CAR-like (NR1J) nuclear receptor provides insight into ancient detoxification mechanisms

    International Nuclear Information System (INIS)

    Cruzeiro, Catarina; Lopes-Marques, Mónica; Ruivo, Raquel; Rodrigues-Oliveira, Nádia; Santos, Miguel M.; Rocha, Maria João; Rocha, Eduardo; Castro, L. Filipe C.

    2016-01-01

    Highlights: • A nuclear receptor orthologue of the NR1J group is isolated from a mollusc. • The molluscan NR1J transactivates gene expression upon exposure to okadaic acid but not a pesticide, esfenvarelate and triclosan. • Lineage specific gene duplications and gene loss have occurred in the NR1J of protostomes with likely impacts on detoxification mechanisms. - Abstract: The origin and diversification of the metazoan endocrine systems represents a fundamental research issue in biology. Nuclear receptors are critical components of these systems. A particular group named VDR/PXR/CAR (NR1I/J) is central in the mediation of detoxification responses. While orthologues have been thoroughly characterized in vertebrates, a sparse representation is currently available for invertebrates. Here, we provide the first isolation and characterization of a lophotrochozoan protostome VDR/PXR/CAR nuclear receptor (NR1J), in the estuarine bivalve the peppery furrow shell (Scrobicularia plana). Using a reporter gene assay, we evaluated the xenobiotic receptor plasticity comparing the human PXR with the S. plana NR1Jβ. Our results show that the molluscan receptor responds to a natural toxin (okadaic acid) in a similar fashion to that reported for other invertebrates. In contrast, the pesticide esfenvalerate displayed a unique response, since it down regulated transactivation at higher concentrations, while for triclosan no response was observed. Additionally, we uncovered lineage specific gene duplications and gene loss in the gene group encoding NRs in protostomes with likely impacts on the complexity of detoxification mechanisms across different phyla. Our findings pave the way for the development of multi-specific sensor tools to screen xenobiotic compounds acting via the NR1I/J group.

  5. Hydraulic root water uptake models: old concerns and new insights

    Science.gov (United States)

    Couvreur, V.; Carminati, A.; Rothfuss, Y.; Meunier, F.; Vanderborght, J.; Javaux, M.

    2014-12-01

    Root water uptake (RWU) affects underground water dynamics, with consequences on plant water availability and groundwater recharge. Even though hydrological and climate models are sensitive to RWU parameters, no consensus exists on the modelling of this process. Back in the 1940ies, Van Den Honert's catenary approach was the first to investigate the use of connected hydraulic resistances to describe water flow in whole plants. However concerns such as the necessary computing when architectures get complex made this approach premature. Now that computing power increased dramatically, hydraulic RWU models are gaining popularity, notably because they naturally produce observed processes like compensatory RWU and hydraulic redistribution. Yet major concerns remain. Some are more fundamental: according to hydraulic principles, plant water potential should equilibrate with soil water potential when the plant does not transpire, which is not a general observation when using current definitions of bulk or average soil water potential. Other concerns regard the validation process: water uptake distribution is not directly measurable, which makes it hard to demonstrate whether or not hydraulic models are more accurate than other models. Eventually parameterization concerns exist: root hydraulic properties are not easily measurable, and would even fluctuate on an hourly basis due to processes like aquaporin gating. While offering opportunities to validate hydraulic RWU models, newly developed observation techniques also make us realize the increasing complexity of processes involved in soil-plant hydrodynamics, such as the change of rhizosphere hydraulic properties with soil drying. Surprisingly, once implemented into hydraulic models, these processes do not necessarily translate into more complex emerging behavior at plant scale, and might justify the use of simplified representations of the soil-plant hydraulic system.

  6. Vaccination of Sheep with a Methanogen Protein Provides Insight into Levels of Antibody in Saliva Needed to Target Ruminal Methanogens.

    Directory of Open Access Journals (Sweden)

    Supatsak Subharat

    Full Text Available Methane is produced in the rumen of ruminant livestock by methanogens and is a major contributor to agricultural greenhouse gases. Vaccination against ruminal methanogens could reduce methane emissions by inducing antibodies in saliva which enter the rumen and impair ability of methanogens to produce methane. Presently, it is not known if vaccination can induce sufficient amounts of antibody in the saliva to target methanogen populations in the rumen and little is known about how long antibody in the rumen remains active. In the current study, sheep were vaccinated twice at a 3-week interval with a model methanogen antigen, recombinant glycosyl transferase protein (rGT2 formulated with one of four adjuvants: saponin, Montanide ISA61, a chitosan thermogel, or a lipid nanoparticle/cationic liposome adjuvant (n = 6/formulation. A control group of sheep (n = 6 was not vaccinated. The highest antigen-specific IgA and IgG responses in both saliva and serum were observed with Montanide ISA61, which promoted levels of salivary antibodies that were five-fold higher than the second most potent adjuvant, saponin. A rGT2-specific IgG standard was used to determine the level of rGT2-specific IgG in serum and saliva. Vaccination with GT2/Montanide ISA61 produced a peak antibody concentration of 7 × 1016 molecules of antigen-specific IgG per litre of saliva, and it was estimated that in the rumen there would be more than 104 molecules of antigen-specific IgG for each methanogen cell. Both IgG and IgA in saliva were shown to be relatively stable in the rumen. Salivary antibody exposed for 1-2 hours to an in vitro simulated rumen environment retained approximately 50% of antigen-binding activity. Collectively, the results from measuring antibody levels and stablility suggest a vaccination-based mitigation strategy for livestock generated methane is in theory feasible.

  7. Dead Sea pollen provides new insights into the paleoenvironment of the southern Levant during MIS 6-5

    Science.gov (United States)

    Chen, Chunzhu; Litt, Thomas

    2018-05-01

    The paleoclimate of the southern Levant, especially during the last interglacial (LIG), is still under debate. Reliable paleovegetation information for this period, as independent evidence to the paleoenvironment, was still missing. In this study, we present a high-resolution pollen record encompassing 147-89 ka from the Dead Sea deep drilling core 5017-1A. The sediment profile is marked by alternations of laminated marl deposits and thick massive halite, indicating lake-level fluctuations. The pollen record suggests that steppe and desert components predominated in the Dead Sea surroundings during the whole investigated interval. The late penultimate glacial (147.3-130.9 ka) and early last glacial (115.5-89.1 ka) were cool and relatively dry, with sub-humid conditions confined to the mountains that sustained moderate amounts of deciduous oaks. Prior to the LIG optimum, a prevalence of desert components and a concomitant increase in frost-sensitive pistachio trees demonstrate the occurrence of an arid initial warming phase (130.9-124.2 ka). The LIG optimum (124.2 ka-115.5 ka) was initiated by an abrupt grass expansion that was followed by a rapid spread of woodlands in the mountains due to increased moisture availability. The remarkable sclerophyllous expansion points to a strong seasonal moisture deficit. These results contradict previous Dead Sea lake-level investigations that suggested pluvial glacials and a warm, dry LIG in the southern Levant. Prominent discrepancies between vegetation and Dead Sea lake stands are also registered at 128-115 ka, and the potential causes are discussed. In particular, while the pollen spectra mirror increased effective moisture during the LIG optimum, the massive halite deposition is indicative of an extremely low lake level. Given that the climate amelioration triggered the migration of early modern humans to the southern Levant, we speculate that the diverse ecosystems in the region provided great potential for their residence

  8. Alternating gender incongruity: a new neuropsychiatric syndrome providing insight into the dynamic plasticity of brain-sex.

    Science.gov (United States)

    Case, Laura K; Ramachandran, Vilayanur S

    2012-05-01

    , which we are currently exploring. Second, we base our hypotheses on ancient and modern associations between the left and right hemispheres and the male and female genders. By providing a case of sharp brain-sex shifts within individuals, we believe that the study of AGI could prove illuminating to scientific understanding of gender, body representation, and the nature of self. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Molecular Phylogeny and Dating of Forsythieae (Oleaceae) Provide Insight into the Miocene History of Eurasian Temperate Shrubs.

    Science.gov (United States)

    Ha, Young-Ho; Kim, Changkyun; Choi, Kyung; Kim, Joo-Hwan

    2018-01-01

    Tribe Forsythieae (Oleaceae), containing two genera ( Abeliophyllum and Forsythia ) and 13 species, is economically important plants used as ornamentals and in traditional medicine. This tribe species occur primarily in mountainous regions of Eurasia with the highest species diversity in East Asia. Here, we examine 11 complete chloroplast genome and nuclear cycloidea2 ( cyc2 ) DNA sequences of 10 Forsythia species and Abeliophyllum distichum using Illumina platform to provide the phylogeny and biogeographic history of the tribe. The chloroplast genomes of the 11 Forsythieae species are highly conserved, except for a deletion of about 400 bp in the accD - psaI region detected only in Abeliophyllum . Within Forsythieae species, analysis of repetitive sequences revealed a total of 51 repeats comprising 26 forward repeats, 22 palindromic repeats, and 3 reverse repeats. Of those, 19 repeats were common and 32 were unique to one or more Forsythieae species. Our phylogenetic analyses supported the monophyly of Forsythia and its sister group is Abeliophyllum using the concatenated dataset of 78 chloroplast genes. Within Forsythia , Forsythia likiangensis and F. giraldiana were basal lineages followed by F. europaea ; the three species are characterized by minutely serrate or entire leaf margins. The remaining species, which are distributed in East Asia, formed two major clades. One clade included F. ovata , F. velutina , and F. japonica ; they are morphologically supported by broadly ovate leaves. Another clade of F. suspensa , F. saxatilis , F. viridissima , and F. koreana characterized by lanceolate leaves (except F. suspensa which have broad ovate leaves). Although cyc2 phylogeny is largely congruent to chloroplast genome phylogeny, we find the discordance between two phylogenies in the position of F. ovata suggesting that introgression of the chloroplast genome from one species into the nuclear background of another by interspecific hybridization in East Asian

  10. Molecular Phylogeny and Dating of Forsythieae (Oleaceae Provide Insight into the Miocene History of Eurasian Temperate Shrubs

    Directory of Open Access Journals (Sweden)

    Young-Ho Ha

    2018-02-01

    Full Text Available Tribe Forsythieae (Oleaceae, containing two genera (Abeliophyllum and Forsythia and 13 species, is economically important plants used as ornamentals and in traditional medicine. This tribe species occur primarily in mountainous regions of Eurasia with the highest species diversity in East Asia. Here, we examine 11 complete chloroplast genome and nuclear cycloidea2 (cyc2 DNA sequences of 10 Forsythia species and Abeliophyllum distichum using Illumina platform to provide the phylogeny and biogeographic history of the tribe. The chloroplast genomes of the 11 Forsythieae species are highly conserved, except for a deletion of about 400 bp in the accD–psaI region detected only in Abeliophyllum. Within Forsythieae species, analysis of repetitive sequences revealed a total of 51 repeats comprising 26 forward repeats, 22 palindromic repeats, and 3 reverse repeats. Of those, 19 repeats were common and 32 were unique to one or more Forsythieae species. Our phylogenetic analyses supported the monophyly of Forsythia and its sister group is Abeliophyllum using the concatenated dataset of 78 chloroplast genes. Within Forsythia, Forsythia likiangensis and F. giraldiana were basal lineages followed by F. europaea; the three species are characterized by minutely serrate or entire leaf margins. The remaining species, which are distributed in East Asia, formed two major clades. One clade included F. ovata, F. velutina, and F. japonica; they are morphologically supported by broadly ovate leaves. Another clade of F. suspensa, F. saxatilis, F. viridissima, and F. koreana characterized by lanceolate leaves (except F. suspensa which have broad ovate leaves. Although cyc2 phylogeny is largely congruent to chloroplast genome phylogeny, we find the discordance between two phylogenies in the position of F. ovata suggesting that introgression of the chloroplast genome from one species into the nuclear background of another by interspecific hybridization in East Asian

  11. Business models for telehealth in the US: analyses and insights

    Directory of Open Access Journals (Sweden)

    Pereira F

    2017-02-01

    Full Text Available Francis Pereira Data Sciences and Operations, Marshall School of Business, University of Southern, Los Angeles, CA, USAAbstract: A growing shortage of medical doctors and nurses, globally, coupled with increasing life expectancy, is generating greater cost pressures on health care, in the US and globally. In this respect, telehealth can help alleviate these pressures, as well as extend medical services to underserved or unserved areas. However, its relatively slow adoption in the US, as well as in other markets, suggests the presence of barriers and challenges. The use of a business model framework helps identify the value proposition of telehealth as well as these challenges, which include identifying the right revenue model, organizational structure, and, perhaps more importantly, the stakeholders in the telehealth ecosystem. Successful and cost-effective deployment of telehealth require a redefinition of the ecosystem and a comprehensive review of all benefits and beneficiaries of such a system; hence a reassessment of all the stakeholders that could benefit from such a system, beyond the traditional patient–health provider–insurer model, and thus “who should pay” for such a system, and the driving efforts of a “keystone” player in developing this initiative would help. Keywords: telehealth, business model framework, stakeholders, ecosystem, VISOR business Model

  12. Natural and molecular history of prolactinoma: insights from a Prlr-/- mouse model.

    Science.gov (United States)

    Bernard, Valérie; Villa, Chiara; Auguste, Aurélie; Lamothe, Sophie; Guillou, Anne; Martin, Agnès; Caburet, Sandrine; Young, Jacques; Veitia, Reiner A; Binart, Nadine

    2018-01-19

    Lactotroph adenoma, also called prolactinoma, is the most common pituitary tumor but little is known about its pathogenesis. Mouse models of prolactinoma can be useful to better understand molecular mechanisms involved in abnormal lactotroph cell proliferation and secretion. We have previously developed a prolactin receptor deficient ( Prlr -/- ) mouse, which develops prolactinoma. The present study aims to explore the natural history of prolactinoma formation in Prlr -/- mice, using hormonal, radiological, histological and molecular analyses to uncover mechanisms involved in lactotroph adenoma development. Prlr -/- females develop large secreting prolactinomas from 12 months of age, with a penetrance of 100%, mimicking human aggressive densely granulated macroprolactinoma, which is a highly secreting subtype. Mean blood PRL measurements reach 14 902 ng/mL at 24 months in Prlr -/- females while PRL levels were below 15 ng/mL in control mice ( p model in ACI rats, we pinpointed 218 concordantly differentially expressed (DE) genes involved in cell cycle, mitosis, cell adhesion molecules, dopaminergic synapse and estrogen signaling. Pathway/gene-set enrichment analyses suggest that the transcriptomic dysregulation in both models of prolactinoma might be mediated by a limited set of transcription factors (i.e., STAT5, STAT3, AhR, ESR1, BRD4, CEBPD, YAP, FOXO1) and kinases (i.e., JAK2, AKT1, BRAF, BMPR1A, CDK8, HUNK, ALK, FGFR1, ILK). Our experimental results and their bioinformatic analysis provide insights into early genomic changes in murine models of the most frequent human pituitary tumor.

  13. Effects of prenatal alcohol exposure (PAE): insights into FASD using mouse models of PAE.

    Science.gov (United States)

    Petrelli, Berardino; Weinberg, Joanne; Hicks, Geoffrey G

    2018-04-01

    The potential impact of prenatal alcohol exposure (PAE) varies considerably among exposed individuals, with some displaying serious alcohol-related effects and many others showing few or no overt signs of fetal alcohol spectrum disorder (FASD). In animal models, variables such as nutrition, genetic background, health, other drugs, and stress, as well as dosage, duration, and gestational timing of exposure to alcohol can all be controlled in a way that is not possible in a clinical situation. In this review we examine mouse models of PAE and focus on those with demonstrated craniofacial malformations, abnormal brain development, or behavioral phenotypes that may be considered FASD-like outcomes. Analysis of these data should provide a valuable tool for researchers wishing to choose the PAE model best suited to their research questions or to investigate established PAE models for FASD comorbidities. It should also allow recognition of patterns linking gestational timing, dosage, and duration of PAE, such as recognizing that binge alcohol exposure(s) during early gestation can lead to severe FASD outcomes. Identified patterns could be particularly insightful and lead to a better understanding of the molecular mechanisms underlying FASD.

  14. The physiology of blood loss and shock: New insights from a human laboratory model of hemorrhage.

    Science.gov (United States)

    Schiller, Alicia M; Howard, Jeffrey T; Convertino, Victor A

    2017-04-01

    The ability to quickly diagnose hemorrhagic shock is critical for favorable patient outcomes. Therefore, it is important to understand the time course and involvement of the various physiological mechanisms that are active during volume loss and that have the ability to stave off hemodynamic collapse. This review provides new insights about the physiology that underlies blood loss and shock in humans through the development of a simulated model of hemorrhage using lower body negative pressure. In this review, we present controlled experimental results through utilization of the lower body negative pressure human hemorrhage model that provide novel insights on the integration of physiological mechanisms critical to the compensation for volume loss. We provide data obtained from more than 250 human experiments to classify human subjects into two distinct groups: those who have a high tolerance and can compensate well for reduced central blood volume (e.g. hemorrhage) and those with low tolerance with poor capacity to compensate.We include the conceptual introduction of arterial pressure and cerebral blood flow oscillations, reflex-mediated autonomic and neuroendocrine responses, and respiration that function to protect adequate tissue oxygenation through adjustments in cardiac output and peripheral vascular resistance. Finally, unique time course data are presented that describe mechanistic events associated with the rapid onset of hemodynamic failure (i.e. decompensatory shock). Impact Statement Hemorrhage is the leading cause of death in both civilian and military trauma. The work submitted in this review is important because it advances the understanding of mechanisms that contribute to the total integrated physiological compensations for inadequate tissue oxygenation (i.e. shock) that arise from hemorrhage. Unlike an animal model, we introduce the utilization of lower body negative pressure as a noninvasive model that allows for the study of progressive

  15. Epigenome remodelling in breast cancer: insights from an early in vitro model of carcinogenesis.

    Science.gov (United States)

    Locke, Warwick J; Clark, Susan J

    2012-11-15

    Epigenetic gene regulation has influence over a diverse range of cellular functions, including the maintenance of pluripotency, differentiation, and cellular identity, and is deregulated in many diseases, including cancer. Whereas the involvement of epigenetic dysregulation in cancer is well documented, much of the mechanistic detail involved in triggering these changes remains unclear. In the current age of genomics, the development of new sequencing technologies has seen an influx of genomic and epigenomic data and drastic improvements in both resolution and coverage. Studies in cancer cell lines and clinical samples using next-generation sequencing are rapidly delivering spectacular insights into the nature of the cancer genome and epigenome. Despite these improvements in technology, the timing and relationship between genetic and epigenetic changes that occur during the process of carcinogenesis are still unclear. In particular, what changes to the epigenome are playing a driving role during carcinogenesis and what influence the temporal nature of these changes has on cancer progression are not known. Understanding the early epigenetic changes driving breast cancer has the exciting potential to provide a novel set of therapeutic targets or early-disease biomarkers or both. Therefore, it is important to find novel systems that permit the study of initial epigenetic events that potentially occur during the first stages of breast cancer. Non-malignant human mammary epithelial cells (HMECs) provide an exciting in vitro model of very early breast carcinogenesis. When grown in culture, HMECs are able to temporarily escape senescence and acquire a pre-malignant breast cancer-like phenotype (variant HMECs, or vHMECs). Cultured HMECs are composed mainly of cells from the basal breast epithelial layer. Therefore, vHMECs are considered to represent the basal-like subtype of breast cancer. The transition from HMECs to vHMECs in culture recapitulates the epigenomic

  16. Improving Perovskite Solar Cells: Insights From a Validated Device Model

    NARCIS (Netherlands)

    Sherkar, Tejas S.; Momblona, Cristina; Gil-Escrig, Lidon; Bolink, Henk J.; Koster, L. Jan Anton

    2017-01-01

    To improve the efficiency of existing perovskite solar cells (PSCs), a detailed understanding of the underlying device physics during their operation is essential. Here, a device model has been developed and validated that describes the operation of PSCs and quantitatively explains the role of

  17. Insights on non-perturbative aspects of TMDs from models

    Energy Technology Data Exchange (ETDEWEB)

    H. Avakian, A. Efremov, P. Schweitzer, O. Teryaev, F. Yuan, P. Zavada

    2009-12-01

    Transverse momentum dependent parton distribution functions are a key ingredient in the description of spin and azimuthal asymmetries in deep-inelastic scattering processes. Recent results from non-perturbative calculations in effective approaches are reviewed, with focus on relations among different parton distribution functions in QCD and models.

  18. Genetic models of absence epilepsy: New concepts and insights

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Stein, J.

    2017-01-01

    The discovery, development and use of genetic rodent models of absence epilepsy have led to a new theory about the origin of absence seizures, which has gained impact within the international epilepsy community. A focal zone has been identified in the perioral region of the somatosensory cortex in

  19. Managing Dog Waste: Campaign Insights from the Health Belief Model

    Science.gov (United States)

    Typhina, Eli; Yan, Changmin

    2014-01-01

    Aiming to help municipalities develop effective education and outreach campaigns to reduce stormwater pollutants, such as pet waste, this study applied the Health Belief Model (HBM) to identify perceptions of dog waste and corresponding collection behaviors from dog owners living in a small U.S. city. Results of 455 online survey responses…

  20. Application of hydropedological insights in hydrological modelling of ...

    African Journals Online (AJOL)

    In this paper the output of a digital soil mapping exercise was used as the soil input into a distributed hydrological model (ACRU) for a test site within the Stevenson-Hamilton Research Supersite, Kruger National Park (South ... The outputs evaluated included both streamflow and soil water content at selected soil profiles.

  1. Modelling inclusive special needs education : Insights from Dutch secondary schools

    NARCIS (Netherlands)

    Van der Bij, T.; Geijsel, F.P.; Garst, G.J.A.; Ten Dam, G.T.M.

    2016-01-01

    Inclusive special needs education is prominent on the international education agenda. Research on the characteristics of inclusive education for students with special needs and schools providing this is scarce, however. Our aim in the present study was therefore to further theory-building with

  2. Modelling Inclusive Special Needs Education: Insights from Dutch Secondary Schools

    Science.gov (United States)

    Van der Bij, T.; Geijsel, F. P.; Garst, G. J. A.; Ten Dam, G. T. M.

    2016-01-01

    Inclusive special needs education is prominent on the international education agenda. Research on the characteristics of inclusive education for students with special needs and schools providing this is scarce, however. Our aim in the present study was therefore to further theory-building with regard to inclusive special needs education. On the…

  3. Insights from quantum cognitive models for organizational decision making

    OpenAIRE

    White, L.C.; Pothos, E. M.; Busemeyer, J. R.

    2015-01-01

    Organizational decision making is often explored with theories from the heuristics and biases research program, which have demonstrated great value as descriptions of how people in organizations make decisions. Nevertheless, rational analysis and classical probability theory are still seen by many as the best accounts of how decisions should be made and classical probability theory is the preferred framework for cognitive modelling for many researchers. The focus of this work is quantum proba...

  4. Rock Burst Mechanics: Insight from Physical and Mathematical Modelling

    Directory of Open Access Journals (Sweden)

    J. Vacek

    2008-01-01

    Full Text Available Rock burst processes in mines are studied by many groups active in the field of geomechanics. Physical and mathematical modelling can be used to better understand the phenomena and mechanisms involved in the bursts. In the present paper we describe both physical and mathematical models of a rock burst occurring in a gallery of a coal mine.For rock bursts (also called bumps to occur, the rock has to possess certain particular rock burst properties leading to accumulation of energy and the potential to release this energy. Such materials may be brittle, or the rock burst may arise at the interfacial zones of two parts of the rock, which have principally different material properties (e.g. in the Poíbram uranium mines.The solution is based on experimental and mathematical modelling. These two methods have to allow the problem to be studied on the basis of three presumptions:· the solution must be time dependent,· the solution must allow the creation of cracks in the rock mass,· the solution must allow an extrusion of rock into an open space (bump effect. 

  5. Cardiac disease and arrhythmogenesis: Mechanistic insights from mouse models

    Directory of Open Access Journals (Sweden)

    Lois Choy

    2016-09-01

    Full Text Available The mouse is the second mammalian species, after the human, in which substantial amount of the genomic information has been analyzed. With advances in transgenic technology, mutagenesis is now much easier to carry out in mice. Consequently, an increasing number of transgenic mouse systems have been generated for the study of cardiac arrhythmias in ion channelopathies and cardiomyopathies. Mouse hearts are also amenable to physical manipulation such as coronary artery ligation and transverse aortic constriction to induce heart failure, radiofrequency ablation of the AV node to model complete AV block and even implantation of a miniature pacemaker to induce cardiac dyssynchrony. Last but not least, pharmacological models, despite being simplistic, have enabled us to understand the physiological mechanisms of arrhythmias and evaluate the anti-arrhythmic properties of experimental agents, such as gap junction modulators, that may be exert therapeutic effects in other cardiac diseases. In this article, we examine these in turn, demonstrating that primary inherited arrhythmic syndromes are now recognized to be more complex than abnormality in a particular ion channel, involving alterations in gene expression and structural remodelling. Conversely, in cardiomyopathies and heart failure, mutations in ion channels and proteins have been identified as underlying causes, and electrophysiological remodelling are recognized pathological features. Transgenic techniques causing mutagenesis in mice are extremely powerful in dissecting the relative contributions of different genes play in producing disease phenotypes. Mouse models can serve as useful systems in which to explore how protein defects contribute to arrhythmias and direct future therapy.

  6. Ambient vibrations of unstable rock slopes - insights from numerical modeling

    Science.gov (United States)

    Burjanek, Jan; Kleinbrod, Ulrike; Fäh, Donat

    2017-04-01

    The recent events in Nepal (2015 M7.8 Gorkha) and New Zealand (2016 M7.8 Kaikoura) highlighted the importance of earthquake-induced landslides, which caused significant damages. Moreover, landslide created dams present a potential developing hazard. In order to reduce the costly consequences of such events it is important to detect and characterize earthquake susceptible rock slope instabilities before an event, and to take mitigation measures. For the characterisation of instable slopes, acquisition of ambient vibrations might be a new alternative to the already existing methods. We present both observations and 3D numerical simulations of the ambient vibrations of unstable slopes. In particular, models of representative real sites have been developed based on detailed terrain mapping and used for the comparison between synthetics and observations. A finite-difference code has been adopted for the seismic wave propagation in a 3D inhomogeneous visco-elastic media with irregular free surface. It utilizes a curvilinear grid for a precise modeling of curved topography and local mesh refinement to make computational mesh finer near the free surface. Topographic site effects, controlled merely by the shape of the topography, do not explain the observed seismic response. In contrast, steeply-dipping compliant fractures have been found to play a key role in fitting observations. Notably, the synthetized response is controlled by inertial mass of the unstable rock, and by stiffness, depth and network density of the fractures. The developed models fit observed extreme amplification levels (factors of 70!) and show directionality as well. This represents a possibility to characterize slope structure and infer depth or volume of the slope instability from the ambient noise recordings in the future.

  7. Giant Glial Cell: New Insight Through Mechanism-Based Modeling

    DEFF Research Database (Denmark)

    Postnov, D. E.; Ryazanova, L. S.; Brazhe, Nadezda

    2008-01-01

    The paper describes a detailed mechanism-based model of a tripartite synapse consisting of P- and R-neurons together with a giant glial cell in the ganglia of the medical leech (Hirudo medicinalis), which is a useful object for experimental studies in situ. We describe the two main pathways...... of the glial cell activation: (1) via IP3 production and Ca2+ release from the endoplasmic reticulum and (2) via increase of the extracellular potassium concentration, glia depolarization, and opening of voltage-dependent Ca2+ channels. We suggest that the second pathway is the more significant...

  8. Modelling insights on the partition of evapotranspiration components across biomes

    Science.gov (United States)

    Fatichi, Simone; Pappas, Christoforos

    2017-04-01

    Recent studies using various methodologies have found a large variability (from 35 to 90%) in the ratio of transpiration to total evapotranspiration (denoted as T:ET) across biomes or even at the global scale. Concurrently, previous results suggest that T:ET is independent of mean precipitation and has a positive correlation with Leaf Area Index (LAI). We used the mechanistic ecohydrological model, T&C, with a refined process-based description of soil resistance and a detailed treatment of canopy biophysics and ecophysiology, to investigate T:ET across multiple biomes. Contrary to observation-based estimates, simulation results highlight a well-constrained range of mean T:ET across biomes that is also robust to perturbations of the most sensitive parameters. Simulated T:ET was confirmed to be independent of average precipitation, while it was found to be uncorrelated with LAI across biomes. Higher values of LAI increase evaporation from interception but suppress ground evaporation with the two effects largely cancelling each other in many sites. These results offer mechanistic, model-based, evidence to the ongoing research about the range of T:ET and the factors affecting its magnitude across biomes.

  9. Elastase-induced pulmonary emphysema: insights from experimental models

    Directory of Open Access Journals (Sweden)

    Mariana A. Antunes

    2011-12-01

    Full Text Available Several distinct stimuli can be used to reproduce histological and functional features of human emphysema, a leading cause of disability and death. Since cigarette smoke is the main cause of emphysema in humans, experimental researches have attempted to reproduce this situation. However, this is an expensive and cumbersome method of emphysema induction, and simpler, more efficacious alternatives have been sought. Among these approaches, elastolytic enzymes have been widely used to reproduce some characteristics of human cigarette smoke-induced disease, such as: augmentation of airspaces, inflammatory cell influx into the lungs, and systemic inflammation. Nevertheless, the use of elastase-induced emphysema models is still controversial, since the disease pathways involved in elastase induction may differ from those occurring in smoke-induced emphysema. This indicates that the choice of an emphysema model may impact the results of new therapies or drugs being tested. The aim of this review is to compare the mechanisms of disease induction in smoke and elastase emphysema models, to describe the differences among various elastase models, and to establish the advantages and disadvantages of elastase-induced emphysema models. More studies are required to shed light on the mechanisms of elastase-induced emphysema.Diversos estímulos podem ser utilizados para reproduzir características histológicas e funcionais do enfisema humano, uma das principais causas de incapacidade e morte. Uma vez que a fumaça de cigarro é a principal causa de enfisema em humanos, estudos experimentais têm tentado reproduzir esta situação. No entanto, esse é um método dispendioso e complicado para a indução do enfisema e, alternativas mais simples e eficazes, têm sido pesquisadas. Entre essas abordagens, enzimas elastolíticas vêm sendo amplamente utilizadas para reproduzir algumas das características do enfisema humano, tais como: aumento dos espaços a

  10. Strabismus and the Oculomotor System: Insights from Macaque Models

    Science.gov (United States)

    Das, Vallabh E.

    2017-01-01

    Disrupting binocular vision in infancy leads to strabismus and oftentimes to a variety of associated visual sensory deficits and oculomotor abnormalities. Investigation of this disorder has been aided by the development of various animal models, each of which has advantages and disadvantages. In comparison to studies of binocular visual responses in cortical structures, investigations of neural oculomotor structures that mediate the misalignment and abnormalities of eye movements have been more recent, and these studies have shown that different brain areas are intimately involved in driving several aspects of the strabismic condition, including horizontal misalignment, dissociated deviations, A and V patterns of strabismus, disconjugate eye movements, nystagmus, and fixation switch. The responses of cells in visual and oculomotor areas that potentially drive the sensory deficits and also eye alignment and eye movement abnormalities follow a general theme of disrupted calibration, lower sensitivity, and poorer specificity compared with the normally developed visual oculomotor system. PMID:28532347

  11. Cellulose synthases: new insights from crystallography and modeling.

    Science.gov (United States)

    Slabaugh, Erin; Davis, Jonathan K; Haigler, Candace H; Yingling, Yaroslava G; Zimmer, Jochen

    2014-02-01

    Detailed information about the structure and biochemical mechanisms of cellulose synthase (CelS) proteins remained elusive until a complex containing the catalytic subunit (BcsA) of CelS from Rhodobacter sphaeroides was crystalized. Additionally, a 3D structure of most of the cytosolic domain of a plant CelS (GhCESA1 from cotton, Gossypium hirsutum) was produced by computational modeling. This predicted structure contributes to our understanding of how plant CelS proteins may be similar and different as compared with BcsA. In this review, we highlight how these structures impact our understanding of the synthesis of cellulose and other extracellular polysaccharides. We show how the structures can be used to generate hypotheses for experiments testing mechanisms of glucan synthesis and translocation in plant CelS. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Hydrologic characteristics of freshwater mussel habitat: novel insights from modeled flows

    Science.gov (United States)

    Drew, C. Ashton; Eddy, Michele; Kwak, Thomas J.; Cope, W. Gregory; Augspurger, Tom

    2018-01-01

    The ability to model freshwater stream habitat and species distributions is limited by the spatially sparse flow data available from long-term gauging stations. Flow data beyond the immediate vicinity of gauging stations would enhance our ability to explore and characterize hydrologic habitat suitability. The southeastern USA supports high aquatic biodiversity, but threats, such as landuse alteration, climate change, conflicting water-resource demands, and pollution, have led to the imperilment and legal protection of many species. The ability to distinguish suitable from unsuitable habitat conditions, including hydrologic suitability, is a key criterion for successful conservation and restoration of aquatic species. We used the example of the critically endangered Tar River Spinymussel (Parvaspina steinstansana) and associated species to demonstrate the value of modeled flow data (WaterFALL™) to generate novel insights into population structure and testable hypotheses regarding hydrologic suitability. With ordination models, we: 1) identified all catchments with potentially suitable hydrology, 2) identified 2 distinct hydrologic environments occupied by the Tar River Spinymussel, and 3) estimated greater hydrological habitat niche breadth of assumed surrogate species associates at the catchment scale. Our findings provide the first demonstrated application of complete, continuous, regional modeled hydrologic data to freshwater mussel distribution and management. This research highlights the utility of modeling and data-mining methods to facilitate further exploration and application of such modeled environmental conditions to inform aquatic species management. We conclude that such an approach can support landscape-scale management decisions that require spatial information at fine resolution (e.g., enhanced National Hydrology Dataset catchments) and broad extent (e.g., multiple river basins).

  13. New insights on geomagnetic storms from observations and modeling

    Energy Technology Data Exchange (ETDEWEB)

    Jordanova, Vania K [Los Alamos National Laboratory

    2009-01-01

    Understanding the response at Earth of the Sun's varying energy output and forecasting geomagnetic activity is of central interest to space science, since intense geomagnetic storms may cause severe damages on technological systems and affect communications. Episodes of southward (Bzmodel (RAM), and investigate the mechanisms responsible for trapping particles and for causing their loss. We find that periods of increased magnetospheric convection coinciding with enhancements of plasma sheet density are needed for strong ring current buildup. During the HSS-driven storm the convection potential is highly variable and causes small sporadic injections into the ring current. The long period of enhanced convection during the CME-driven storm causes a continuous ring current injection penetrating to lower L shells and stronger ring current buildup.

  14. IR sensor design insight from missile-plume prediction models

    Science.gov (United States)

    Rapanotti, John L.; Gilbert, Bruno; Richer, Guy; Stowe, Robert

    2002-08-01

    Modern anti-tank missiles and the requirement of rapid deployment have significantly reduced the use of passive armour in protecting land vehicles. Vehicle survivability is becoming more dependent on sensors, computers and countermeasures to detect and avoid threats. An analysis of missile propellants suggests that missile detection based on plume characteristics alone may be more difficult than anticipated. Currently, the passive detection of missiles depends on signatures with a significant ultraviolet component. This approach is effective in detecting anti-aircraft missiles that rely on powerful motors to pursue high-speed aircraft. The high temperature exhaust from these missiles contains significant levels of carbon dioxide, water and, often, metal oxides such as alumina. The plumes emits strongest in the infrared, 1 to 5micrometers , regions with a significant component of the signature extending into the ultraviolet domain. Many anti-tank missiles do not need the same level of propulsion and radiate significantly less. These low velocity missiles, relying on the destructive force of shaped-charge warhead, are more difficult to detect. There is virtually no ultraviolet component and detection based on UV sensors is impractical. The transition in missile detection from UV to IR is reasonable, based on trends in imaging technology, but from the analysis presented in this paper even IR imagers may have difficulty in detecting missile plumes. This suggests that the emphasis should be placed in the detection of the missile hard body in the longer wavelengths of 8 to 12micrometers . The analysis described in this paper is based on solution of the governing equations of plume physics and chemistry. These models will be used to develop better sensors and threat detection algorithms.

  15. Seismic variability of subduction thrust faults: Insights from laboratory models

    Science.gov (United States)

    Corbi, F.; Funiciello, F.; Faccenna, C.; Ranalli, G.; Heuret, A.

    2011-06-01

    Laboratory models are realized to investigate the role of interface roughness, driving rate, and pressure on friction dynamics. The setup consists of a gelatin block driven at constant velocity over sand paper. The interface roughness is quantified in terms of amplitude and wavelength of protrusions, jointly expressed by a reference roughness parameter obtained by their product. Frictional behavior shows a systematic dependence on system parameters. Both stick slip and stable sliding occur, depending on driving rate and interface roughness. Stress drop and frequency of slip episodes vary directly and inversely, respectively, with the reference roughness parameter, reflecting the fundamental role for the amplitude of protrusions. An increase in pressure tends to favor stick slip. Static friction is a steeply decreasing function of the reference roughness parameter. The velocity strengthening/weakening parameter in the state- and rate-dependent dynamic friction law becomes negative for specific values of the reference roughness parameter which are intermediate with respect to the explored range. Despite the simplifications of the adopted setup, which does not address the problem of off-fault fracturing, a comparison of the experimental results with the depth distribution of seismic energy release along subduction thrust faults leads to the hypothesis that their behavior is primarily controlled by the depth- and time-dependent distribution of protrusions. A rough subduction fault at shallow depths, unable to produce significant seismicity because of low lithostatic pressure, evolves into a moderately rough, velocity-weakening fault at intermediate depths. The magnitude of events in this range is calibrated by the interplay between surface roughness and subduction rate. At larger depths, the roughness further decreases and stable sliding becomes gradually more predominant. Thus, although interplate seismicity is ultimately controlled by tectonic parameters (velocity of

  16. Transcriptomes and expression profiling of deep-sea corals from the Red Sea provide insight into the biology of azooxanthellate corals

    KAUST Repository

    Yum, Lauren

    2017-07-19

    Despite the importance of deep-sea corals, our current understanding of their ecology and evolution is limited due to difficulties in sampling and studying deep-sea environments. Moreover, a recent re-evaluation of habitat limitations has been suggested after characterization of deep-sea corals in the Red Sea, where they live at temperatures of above 20 °C at low oxygen concentrations. To gain further insight into the biology of deep-sea corals, we produced reference transcriptomes and studied gene expression of three deep-sea coral species from the Red Sea, i.e. Dendrophyllia sp., Eguchipsammia fistula, and Rhizotrochus typus. Our analyses suggest that deep-sea coral employ mitochondrial hypometabolism and anaerobic glycolysis to manage low oxygen conditions present in the Red Sea. Notably, we found expression of genes related to surface cilia motion that presumably enhance small particle transport rates in the oligotrophic deep-sea environment. This is the first study to characterize transcriptomes and in situ gene expression for deep-sea corals. Our work offers several mechanisms by which deep-sea corals might cope with the distinct environmental conditions present in the Red Sea As such, our data provide direction for future research and further insight to organismal response of deep-sea coral to environmental change and ocean warming.

  17. Transcriptomes and expression profiling of deep-sea corals from the Red Sea provide insight into the biology of azooxanthellate corals.

    Science.gov (United States)

    Yum, Lauren K; Baumgarten, Sebastian; Röthig, Till; Roder, Cornelia; Roik, Anna; Michell, Craig; Voolstra, Christian R

    2017-07-25

    Despite the importance of deep-sea corals, our current understanding of their ecology and evolution is limited due to difficulties in sampling and studying deep-sea environments. Moreover, a recent re-evaluation of habitat limitations has been suggested after characterization of deep-sea corals in the Red Sea, where they live at temperatures of above 20 °C at low oxygen concentrations. To gain further insight into the biology of deep-sea corals, we produced reference transcriptomes and studied gene expression of three deep-sea coral species from the Red Sea, i.e. Dendrophyllia sp., Eguchipsammia fistula, and Rhizotrochus typus. Our analyses suggest that deep-sea coral employ mitochondrial hypometabolism and anaerobic glycolysis to manage low oxygen conditions present in the Red Sea. Notably, we found expression of genes related to surface cilia motion that presumably enhance small particle transport rates in the oligotrophic deep-sea environment. This is the first study to characterize transcriptomes and in situ gene expression for deep-sea corals. Our work offers several mechanisms by which deep-sea corals might cope with the distinct environmental conditions present in the Red Sea As such, our data provide direction for future research and further insight to organismal response of deep-sea coral to environmental change and ocean warming.

  18. Transcriptomes and expression profiling of deep-sea corals from the Red Sea provide insight into the biology of azooxanthellate corals

    KAUST Repository

    Yum, Lauren; Baumgarten, Sebastian; Rö thig, Till; Roder, Cornelia; Roik, Anna Krystyna; Michell, Craig; Voolstra, Christian R.

    2017-01-01

    Despite the importance of deep-sea corals, our current understanding of their ecology and evolution is limited due to difficulties in sampling and studying deep-sea environments. Moreover, a recent re-evaluation of habitat limitations has been suggested after characterization of deep-sea corals in the Red Sea, where they live at temperatures of above 20 °C at low oxygen concentrations. To gain further insight into the biology of deep-sea corals, we produced reference transcriptomes and studied gene expression of three deep-sea coral species from the Red Sea, i.e. Dendrophyllia sp., Eguchipsammia fistula, and Rhizotrochus typus. Our analyses suggest that deep-sea coral employ mitochondrial hypometabolism and anaerobic glycolysis to manage low oxygen conditions present in the Red Sea. Notably, we found expression of genes related to surface cilia motion that presumably enhance small particle transport rates in the oligotrophic deep-sea environment. This is the first study to characterize transcriptomes and in situ gene expression for deep-sea corals. Our work offers several mechanisms by which deep-sea corals might cope with the distinct environmental conditions present in the Red Sea As such, our data provide direction for future research and further insight to organismal response of deep-sea coral to environmental change and ocean warming.

  19. Comparative Study of Lectin Domains in Model Species: New Insights into Evolutionary Dynamics

    Directory of Open Access Journals (Sweden)

    Sofie Van Holle

    2017-05-01

    Full Text Available Lectins are present throughout the plant kingdom and are reported to be involved in diverse biological processes. In this study, we provide a comparative analysis of the lectin families from model species in a phylogenetic framework. The analysis focuses on the different plant lectin domains identified in five representative core angiosperm genomes (Arabidopsis thaliana, Glycine max, Cucumis sativus, Oryza sativa ssp. japonica and Oryza sativa ssp. indica. The genomes were screened for genes encoding lectin domains using a combination of Basic Local Alignment Search Tool (BLAST, hidden Markov models, and InterProScan analysis. Additionally, phylogenetic relationships were investigated by constructing maximum likelihood phylogenetic trees. The results demonstrate that the majority of the lectin families are present in each of the species under study. Domain organization analysis showed that most identified proteins are multi-domain proteins, owing to the modular rearrangement of protein domains during evolution. Most of these multi-domain proteins are widespread, while others display a lineage-specific distribution. Furthermore, the phylogenetic analyses reveal that some lectin families evolved to be similar to the phylogeny of the plant species, while others share a closer evolutionary history based on the corresponding protein domain architecture. Our results yield insights into the evolutionary relationships and functional divergence of plant lectins.

  20. Top Mysteries of the Mind: Insights From the Default Space Model of Consciousness

    Directory of Open Access Journals (Sweden)

    Ravinder Jerath

    2018-04-01

    Full Text Available Aside from the nature of consciousness itself, there are still many unsolved problems in the neurosciences. Despite the vast and quickly growing body of work in this field, we still find ourselves perplexed at seemingly simple qualities of our mental being such as why we need to sleep. The neurosciences are at least beginning to take a hold on these mysteries and are working toward solving them. We hold a perspective that metastable consciousness models, specifically the Default Space Model (DSM, provide insights into these mysteries. In this perspective article, we explore some of these curious questions in order to elucidate the interesting points they bring up. The DSM is a dynamic, global theory of consciousness that involves the maintenance of an internal, 3D simulation of the external, physical world which is the foundation and structure of consciousness. This space is created and filled by multiple frequencies of membrane potential oscillations throughout the brain and body which are organized, synchronized and harmonized by the thalamus. The veracity of the DSM is highlighted here in its ability to further understanding of some of the most puzzling problems in neuroscience.

  1. Correlation of proteome-wide changes with social immunity behaviors provides insight into resistance to the parasitic mite, Varroa destructor, in the honey bee (Apis mellifera).

    Science.gov (United States)

    Parker, Robert; Guarna, M Marta; Melathopoulos, Andony P; Moon, Kyung-Mee; White, Rick; Huxter, Elizabeth; Pernal, Stephen F; Foster, Leonard J

    2012-06-29

    Disease is a major factor driving the evolution of many organisms. In honey bees, selection for social behavioral responses is the primary adaptive process facilitating disease resistance. One such process, hygienic behavior, enables bees to resist multiple diseases, including the damaging parasitic mite Varroa destructor. The genetic elements and biochemical factors that drive the expression of these adaptations are currently unknown. Proteomics provides a tool to identify proteins that control behavioral processes, and these proteins can be used as biomarkers to aid identification of disease tolerant colonies. We sampled a large cohort of commercial queen lineages, recording overall mite infestation, hygiene, and the specific hygienic response to V. destructor. We performed proteome-wide correlation analyses in larval integument and adult antennae, identifying several proteins highly predictive of behavior and reduced hive infestation. In the larva, response to wounding was identified as a key adaptive process leading to reduced infestation, and chitin biosynthesis and immune responses appear to represent important disease resistant adaptations. The speed of hygienic behavior may be underpinned by changes in the antenna proteome, and chemosensory and neurological processes could also provide specificity for detection of V. destructor in antennae. Our results provide, for the first time, some insight into how complex behavioural adaptations manifest in the proteome of honey bees. The most important biochemical correlations provide clues as to the underlying molecular mechanisms of social and innate immunity of honey bees. Such changes are indicative of potential divergence in processes controlling the hive-worker maturation.

  2. On the Modelling of Biological Patterns with Mechanochemical Models: Insights from Analysis and Computation

    KAUST Repository

    Moreo, P.

    2009-11-14

    The diversity of biological form is generated by a relatively small number of underlying mechanisms. Consequently, mathematical and computational modelling can, and does, provide insight into how cellular level interactions ultimately give rise to higher level structure. Given cells respond to mechanical stimuli, it is therefore important to consider the effects of these responses within biological self-organisation models. Here, we consider the self-organisation properties of a mechanochemical model previously developed by three of the authors in Acta Biomater. 4, 613-621 (2008), which is capable of reproducing the behaviour of a population of cells cultured on an elastic substrate in response to a variety of stimuli. In particular, we examine the conditions under which stable spatial patterns can emerge with this model, focusing on the influence of mechanical stimuli and the interplay of non-local phenomena. To this end, we have performed a linear stability analysis and numerical simulations based on a mixed finite element formulation, which have allowed us to study the dynamical behaviour of the system in terms of the qualitative shape of the dispersion relation. We show that the consideration of mechanotaxis, namely changes in migration speeds and directions in response to mechanical stimuli alters the conditions for pattern formation in a singular manner. Furthermore without non-local effects, responses to mechanical stimuli are observed to result in dispersion relations with positive growth rates at arbitrarily large wavenumbers, in turn yielding heterogeneity at the cellular level in model predictions. This highlights the sensitivity and necessity of non-local effects in mechanically influenced biological pattern formation models and the ultimate failure of the continuum approximation in their absence. © 2009 Society for Mathematical Biology.

  3. Insights Into the Bifunctional Aphidicolan-16-ß-ol Synthase Through Rapid Biomolecular Modeling Approaches.

    Science.gov (United States)

    Hirte, Max; Meese, Nicolas; Mertz, Michael; Fuchs, Monika; Brück, Thomas B

    2018-01-01

    Diterpene synthases catalyze complex, multi-step C-C coupling reactions thereby converting the universal, aliphatic precursor geranylgeranyl diphosphate into diverse olefinic macrocylces that form the basis for the structural diversity of the diterpene natural product family. Since catalytically relevant crystal structures of diterpene synthases are scarce, homology based biomolecular modeling techniques offer an alternative route to study the enzyme's reaction mechanism. However, precise identification of catalytically relevant amino acids is challenging since these models require careful preparation and refinement techniques prior to substrate docking studies. Targeted amino acid substitutions in this protein class can initiate premature quenching of the carbocation centered reaction cascade. The structural characterization of those alternative cyclization products allows for elucidation of the cyclization reaction cascade and provides a new source for complex macrocyclic synthons. In this study, new insights into structure and function of the fungal, bifunctional Aphidicolan-16-ß-ol synthase were achieved using a simplified biomolecular modeling strategy. The applied refinement methodologies could rapidly generate a reliable protein-ligand complex, which provides for an accurate in silico identification of catalytically relevant amino acids. Guided by our modeling data, ACS mutations lead to the identification of the catalytically relevant ACS amino acid network I626, T657, Y658, A786, F789, and Y923. Moreover, the ACS amino acid substitutions Y658L and D661A resulted in a premature termination of the cyclization reaction cascade en-route from syn-copalyl diphosphate to Aphidicolan-16-ß-ol. Both ACS mutants generated the diterpene macrocycle syn-copalol and a minor, non-hydroxylated labdane related diterpene, respectively. Our biomolecular modeling and mutational studies suggest that the ACS substrate cyclization occurs in a spatially restricted location of

  4. Insights Into the Bifunctional Aphidicolan-16-ß-ol Synthase Through Rapid Biomolecular Modeling Approaches

    Directory of Open Access Journals (Sweden)

    Max Hirte

    2018-04-01

    Full Text Available Diterpene synthases catalyze complex, multi-step C-C coupling reactions thereby converting the universal, aliphatic precursor geranylgeranyl diphosphate into diverse olefinic macrocylces that form the basis for the structural diversity of the diterpene natural product family. Since catalytically relevant crystal structures of diterpene synthases are scarce, homology based biomolecular modeling techniques offer an alternative route to study the enzyme's reaction mechanism. However, precise identification of catalytically relevant amino acids is challenging since these models require careful preparation and refinement techniques prior to substrate docking studies. Targeted amino acid substitutions in this protein class can initiate premature quenching of the carbocation centered reaction cascade. The structural characterization of those alternative cyclization products allows for elucidation of the cyclization reaction cascade and provides a new source for complex macrocyclic synthons. In this study, new insights into structure and function of the fungal, bifunctional Aphidicolan-16-ß-ol synthase were achieved using a simplified biomolecular modeling strategy. The applied refinement methodologies could rapidly generate a reliable protein-ligand complex, which provides for an accurate in silico identification of catalytically relevant amino acids. Guided by our modeling data, ACS mutations lead to the identification of the catalytically relevant ACS amino acid network I626, T657, Y658, A786, F789, and Y923. Moreover, the ACS amino acid substitutions Y658L and D661A resulted in a premature termination of the cyclization reaction cascade en-route from syn-copalyl diphosphate to Aphidicolan-16-ß-ol. Both ACS mutants generated the diterpene macrocycle syn-copalol and a minor, non-hydroxylated labdane related diterpene, respectively. Our biomolecular modeling and mutational studies suggest that the ACS substrate cyclization occurs in a spatially

  5. Insights into the bifunctional Aphidicolan-16-ß-ol synthase through rapid biomolecular modelling approaches

    Science.gov (United States)

    Hirte, Max; Meese, Nicolas; Mertz, Michael; Fuchs, Monika; Brück, Thomas B.

    2018-04-01

    Diterpene synthases catalyze complex, multi-step C-C coupling reactions thereby converting the universal, aliphatic precursor geranylgeranyl diphosphate into diverse olefinic macrocylces that form the basis for the structural diversity of the diterpene natural product family. Since catalytically relevant crystal structures of diterpene synthases are scarce, homology based biomolecular modelling techniques offer an alternative route to study the enzyme’s reaction mechanism. However, precise identification of catalytically relevant amino acids is challenging since these models require careful preparation and refinement techniques prior to substrate docking studies. Targeted amino acid substitutions in this protein class can initiate premature quenching of the carbocation centered reaction cascade. The structural characterization of those alternative cyclization products allows for elucidation of the cyclization reaction cascade and provides a new source for complex macrocyclic synthons. In this study, new insights into structure and function of the fungal, bifunctional Aphidicolan-16-ß-ol synthase were achieved using a simplified biomolecular modelling strategy. The applied refinement methodologies could rapidly generate a reliable protein-ligand complex, which provides for an accurate in silico identification of catalytically relevant amino acids. Guided by our modelling data, ACS mutations lead to the identification of the catalytically relevant ACS amino acid network I626, T657, Y658, A786, F789 and Y923. Moreover, the ACS amino acid substitutions Y658L and D661A resulted in a premature termination of the cyclization reaction cascade en-route from syn-copalyl diphosphate to Aphidicolan-16-ß-ol. Both ACS mutants generated the diterpene macrocycle syn-copalol and a minor, non-hydroxylated labdane related diterpene, respectively. Our biomolecular modelling and mutational studies suggest that the ACS substrate cyclization occurs in a spatially restricted location

  6. Learning from a paradox: recent insights into Fanconi anaemia through studying mouse models

    Directory of Open Access Journals (Sweden)

    Sietske T. Bakker

    2013-01-01

    Full Text Available Fanconi anaemia (FA is a rare autosomal recessive or X-linked inherited disease characterised by an increased incidence of bone marrow failure (BMF, haematological malignancies and solid tumours. Cells from individuals with FA show a pronounced sensitivity to DNA interstrand crosslink (ICL-inducing agents, which manifests as G2-M arrest, chromosomal aberrations and reduced cellular survival. To date, mutations in at least 15 different genes have been identified that cause FA; the products of all of these genes are thought to function together in the FA pathway, which is essential for ICL repair. Rapidly following the discovery of FA genes, mutant mice were generated to study the disease and the affected pathway. These mutant mice all show the characteristic cellular ICL-inducing agent sensitivity, but only partially recapitulate the developmental abnormalities, anaemia and cancer predisposition seen in individuals with FA. Therefore, the usefulness of modelling FA in mice has been questioned. In this Review, we argue that such scepticism is unjustified. We outline that haematopoietic defects and cancer predisposition are manifestations of FA gene defects in mice, albeit only in certain genetic backgrounds and under certain conditions. Most importantly, recent work has shown that developmental defects in FA mice also arise with concomitant inactivation of acetaldehyde metabolism, giving a strong clue about the nature of the endogenous lesion that must be repaired by the functional FA pathway. This body of work provides an excellent example of a paradox in FA research: that the dissimilarity, rather than the similarity, between mice and humans can provide insight into human disease. We expect that further study of mouse models of FA will help to uncover the mechanistic background of FA, ultimately leading to better treatment options for the disease.

  7. High-frequency DOC and nitrate measurements provide new insights into their export and their relationships to rainfall-runoff processes

    Science.gov (United States)

    Schwab, Michael; Klaus, Julian; Pfister, Laurent; Weiler, Markus

    2015-04-01

    Over the past decades, stream sampling protocols for environmental tracers were often limited by logistical and technological constraints. Long-term sampling programs would typically rely on weekly sampling campaigns, while high-frequency sampling would remain restricted to a few days or hours at best. We stipulate that the currently predominant sampling protocols are too coarse to capture and understand the full amplitude of rainfall-runoff processes and its relation to water quality fluctuations. Weekly sampling protocols are not suited to get insights into the hydrological system during high flow conditions. Likewise, high frequency measurements of a few isolated events do not allow grasping inter-event variability in contributions and processes. Our working hypothesis is based on the potential of a new generation of field-deployable instruments for measuring environmental tracers at high temporal frequencies over an extended period. With this new generation of instruments we expect to gain new insights into rainfall-runoff dynamics, both at intra- and inter-event scales. Here, we present the results of one year of DOC and nitrate measurements with the field deployable UV-Vis spectrometer spectro::lyser (scan Messtechnik GmbH). The instrument measures the absorption spectrum from 220 to 720 nm in situ and at high frequencies and derives DOC and nitrate concentrations. The measurements were carried out at 15 minutes intervals in the Weierbach catchment (0.47 km2) in Luxemburg. This fully forested catchment is characterized by cambisol soils and fractured schist as underlying bedrock. The time series of DOC and nitrate give insights into the high frequency dynamics of stream water. Peaks in DOC concentrations are closely linked to discharge peaks that occur during or right after a rainfall event. Those first discharge peaks can be linked to fast near surface runoff processes and are responsible for a remarkable amount of DOC export. A special characterisation of

  8. Social deprivation and burden of influenza: Testing hypotheses and gaining insights from a simulation model for the spread of influenza

    Directory of Open Access Journals (Sweden)

    Ayaz Hyder

    2015-06-01

    Full Text Available Factors associated with the burden of influenza among vulnerable populations have mainly been identified using statistical methodologies. Complex simulation models provide mechanistic explanations, in terms of spatial heterogeneity and contact rates, while controlling other factors and may be used to better understand statistical patterns and, ultimately, design optimal population-level interventions. We extended a sophisticated simulation model, which was applied to forecast epidemics and validated for predictive ability, to identify mechanisms for the empirical relationship between social deprivation and the burden of influenza. Our modeled scenarios and associated epidemic metrics systematically assessed whether neighborhood composition and/or spatial arrangement could qualitatively replicate this empirical relationship. We further used the model to determine consequences of local-scale heterogeneities on larger scale disease spread. Our findings indicated that both neighborhood composition and spatial arrangement were critical to qualitatively match the empirical relationship of interest. Also, when social deprivation was fully included in the model, we observed lower age-based attack rates and greater delay in epidemic peak week in the most socially deprived neighborhoods. Insights from simulation models complement current understandings from statistical-based association studies. Additional insights from our study are: (1 heterogeneous spatial arrangement of neighborhoods is a necessary condition for simulating observed disparities in the burden of influenza and (2 unmeasured factors may lead to a better quantitative match between simulated and observed rate ratio in the burden of influenza between the most and least socially deprived populations.

  9. An optimisation approach for capacity planning: modelling insights and empirical findings from a tactical perspective

    Directory of Open Access Journals (Sweden)

    Andréa Nunes Carvalho

    2017-09-01

    Full Text Available Abstract The academic literature presents a research-practice gap on the application of decision support tools to address tactical planning problems in real-world organisations. This paper addresses this gap and extends a previous action research relative to an optimisation model applied for tactical capacity planning in an engineer-to-order industrial setting. The issues discussed herein raise new insights to better understand the practical results that can be achieved through the proposed model. The topics presented include the modelling of objectives, the representation of the production process and the costing approach, as well as findings regarding managerial decisions and the scope of action considered. These insights may inspire ideas to academics and practitioners when developing tools for capacity planning problems in similar contexts.

  10. Sources of Sahelian-Sudan moisture: Insights from a moisture-tracing atmospheric model

    Science.gov (United States)

    Salih, Abubakr A. M.; Zhang, Qiong; Pausata, Francesco S. R.; Tjernström, Michael

    2016-07-01

    The summer rainfall across Sahelian-Sudan is one of the main sources of water for agriculture, human, and animal needs. However, the rainfall is characterized by large interannual variability, which has attracted extensive scientific efforts to understand it. This study attempts to identify the source regions that contribute to the Sahelian-Sudan moisture budget during July through September. We have used an atmospheric general circulation model with an embedded moisture-tracing module (Community Atmosphere Model version 3), forced by observed (1979-2013) sea-surface temperatures. The result suggests that about 40% of the moisture comes with the moisture flow associated with the seasonal migration of the Intertropical Convergence Zone (ITCZ) and originates from Guinea Coast, central Africa, and the Western Sahel. The Mediterranean Sea, Arabian Peninsula, and South Indian Ocean regions account for 10.2%, 8.1%, and 6.4%, respectively. Local evaporation and the rest of the globe supply the region with 20.3% and 13.2%, respectively. We also compared the result from this study to a previous analysis that used the Lagrangian model FLEXPART forced by ERA-Interim. The two approaches differ when comparing individual regions, but are in better agreement when neighboring regions of similar atmospheric flow features are grouped together. Interannual variability with the rainfall over the region is highly correlated with contributions from regions that are associated with the ITCZ movement, which is in turn linked to the Atlantic Multidecadal Oscillation. Our result is expected to provide insights for the effort on seasonal forecasting of the rainy season over Sahelian Sudan.

  11. Seismic attenuation in fractured porous media: insights from a hybrid numerical and analytical model

    International Nuclear Information System (INIS)

    Ekanem, A M; Li, X Y; Chapman, M; Main, I G

    2015-01-01

    Seismic attenuation in fluid-saturated porous rocks can occur by geometric spreading, wave scattering or the internal dissipation of energy, most likely due to the squirt-flow mechanism. In principle, the pattern of seismic attenuation recorded on an array of sensors contains information about the medium, in terms of material heterogeneity and anisotropy, as well as material properties such as porosity, crack density, and pore-fluid composition and mobility. In practice, this inverse problem is challenging. Here we provide some insights into the effects of internal dissipation by analysing synthetic data produced by a hybrid numerical and analytical model for seismic wave propagation in a fractured medium embedded within a layered geological structure. The model is made up of one anisotropic and three isotropic horizontal layers. The anisotropic layer consists of a porous, fluid-saturated material containing vertically aligned inclusions representing a set of fractures. This combination allows squirt-flow to occur between the pores in the matrix and the model fractures. Our results show that the fluid mobility and the associated relaxation time of the fluid-pressure gradient control the frequency range over which attenuation occurs. This induced attenuation increases with incidence angle and azimuth away from the fracture strike-direction. Azimuthal variations in the induced attenuation are elliptical allowing the fracture orientations to be obtained from the axes of the ellipse. These observations hold out the potential of using seismic attenuation as an additional diagnostic in the characterisation of rock formations for a variety of applications including hydrocarbon exploration and production, subsurface storage of CO 2 , and geothermal energy extraction. (paper)

  12. Neuroprotective effects of estrogen in CNS injuries: insights from animal models

    Directory of Open Access Journals (Sweden)

    Raghava N

    2017-07-01

    Full Text Available Narayan Raghava,1 Bhaskar C Das,2 Swapan K Ray1 1Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA; 2Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA Abstract: Among the estrogens that are biosynthesized in the human body, 17β-estradiol (estradiol or E2 is the most common and the best estrogen for neuroprotection in animal models of the central nervous system (CNS injuries such as spinal cord injury (SCI, traumatic brain injury (TBI, and ischemic brain injury (IBI. These CNS injuries are not only serious health problems, but also enormous economic burden on the patients, their families, and the society at large. Studies from animal models of these CNS injuries provide insights into the multiple neuroprotective mechanisms of E2 and also suggest the possibility of translating the therapeutic efficacy of E2 in the treatment SCI, TBI, and IBI in humans in the near future. The pathophysiology of these injuries includes loss of motor function in the limbs, arms and their extremities, cognitive deficit, and many other serious consequences including life-threatening paralysis, infection, and even death. The potential application of E2 therapy to treat the CNS injuries may become a trend as the results are showing significant therapeutic benefits of E2 for neuroprotection when administered into the animal models of SCI, TBI, and IBI. This article describes the plausible mechanisms how E2 works with or without the involvement of estrogen receptors and provides an overview of the known neuroprotective effects of E2 in these three CNS injuries in different animal models. Because activation of estrogen receptors has profound implications in maintaining and also affecting normal physiology, there are notable impediments in translating E2 therapy to the clinics for neuroprotection in CNS injuries in humans. While E2 may not yet be the sole molecule for

  13. Insights about data assimilation frameworks for integrating GRACE with hydrological models

    Science.gov (United States)

    Schumacher, Maike; Kusche, Jürgen; Van Dijk, Albert I. J. M.; Döll, Petra; Schuh, Wolf-Dieter

    2016-04-01

    Improving the understanding of changes in the water cycle represents a challenging objective that requires merging information from various disciplines. Debates exist on selecting an appropriate assimilation technique to integrate GRACE-derived terrestrial water storage changes (TWSC) into hydrological models in order to downscale and disaggregate GRACE TWSC, overcome model limitations, and improve monitoring and forecast skills. Yet, the effect of the specific data assimilation technique in conjunction with ill-conditioning, colored noise, resolution mismatch between GRACE and model, and other complications is still unclear. Due to its simplicity, ensemble Kalman filters or smoothers (EnKF/S) are often applied. In this study, we show that modification of the filter approach might open new avenues to improve the integration process. Particularly, we discuss an improved calibration and data assimilation (C/DA) framework (Schumacher et al., 2016), which is based on the EnKF and was extended by the square root analysis scheme (SQRA) and the singular evolutive interpolated Kalman (SEIK) filter. In addition, we discuss an off-line data blending approach (Van Dijk et al., 2014) that offers the chance to merge multi-model ensembles with GRACE observations. The investigations include: (i) a theoretical comparison, focusing on similarities and differences of the conceptual formulation of the filter algorithms, (ii) a practical comparison, for which the approaches were applied to an ensemble of runs of the WaterGAP Global Hydrology Model (WGHM), as well as (iii) an impact assessment of the GRACE error structure on C/DA results. First, a synthetic experiment over the Mississippi River Basin (USA) was used to gain insights about the C/DA set-up before applying it to real data. The results indicated promising performances when considering alternative methods, e.g. applying the SEIK algorithm improved the correlation coefficient and root mean square error (RMSE) of TWSC by 0

  14. Ancient duplications and functional divergence in the interferon regulatory factors of vertebrates provide insights into the evolution of vertebrate immune systems.

    Science.gov (United States)

    Du, Kang; Zhong, Zaixuan; Fang, Chengchi; Dai, Wei; Shen, Yanjun; Gan, Xiaoni; He, Shunping

    2018-04-01

    Interferon regulatory factors (IRFs) were first discovered as transcription factors that regulate the transcription of human interferon (IFN)-β. Increasing evidence shows that they might be important players involved in Adaptive immune system (AIS) evolution. Although numbers of IRFs have been identified in chordates, the evolutionary history and functional diversity of this gene family during the early evolution of vertebrates have remained obscure. Using IRF HMM profile and HMMER searches, we identified 148 IRFs in 11 vertebrates and 4 protochordates. For them, we reconstructed the phylogenetic relationships, determined the synteny conservation, investigated the profile of natural selection, and analyzed the expression patterns in four "living fossil" vertebrates: lamprey, elephant shark, coelacanth and bichir. The results from phylogeny and synteny analysis imply that vertebrate IRFs evolved from three predecessors, instead of four as suggested in a previous study, as results from an ancient duplication followed by special expansions and lost during the vertebrate evolution. The profile of natural selection and expression reveals functional dynamics during the process. Together, they suggest that the 2nd whole-genome duplication (2WGD) provided raw materials for innovation in the IRF family, and that the birth of type-I IFN might be an important factor inducing the establishment of IRF-mediated immune networks. As a member involved in the AIS evolution, IRF provide insights into the process and mechanism involved in the complexity and novelties of vertebrate immune systems. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. A high-quality genome assembly of quinoa provides insights into the molecular basis of salt bladder-based salinity tolerance and the exceptional nutritional value

    Science.gov (United States)

    Zou, Changsong; Chen, Aojun; Xiao, Lihong; Muller, Heike M; Ache, Peter; Haberer, Georg; Zhang, Meiling; Jia, Wei; Deng, Ping; Huang, Ru; Lang, Daniel; Li, Feng; Zhan, Dongliang; Wu, Xiangyun; Zhang, Hui; Bohm, Jennifer; Liu, Renyi; Shabala, Sergey; Hedrich, Rainer; Zhu, Jian-Kang; Zhang, Heng

    2017-01-01

    Chenopodium quinoa is a halophytic pseudocereal crop that is being cultivated in an ever-growing number of countries. Because quinoa is highly resistant to multiple abiotic stresses and its seed has a better nutritional value than any other major cereals, it is regarded as a future crop to ensure global food security. We generated a high-quality genome draft using an inbred line of the quinoa cultivar Real. The quinoa genome experienced one recent genome duplication about 4.3 million years ago, likely reflecting the genome fusion of two Chenopodium parents, in addition to the γ paleohexaploidization reported for most eudicots. The genome is highly repetitive (64.5% repeat content) and contains 54 438 protein-coding genes and 192 microRNA genes, with more than 99.3% having orthologous genes from glycophylic species. Stress tolerance in quinoa is associated with the expansion of genes involved in ion and nutrient transport, ABA homeostasis and signaling, and enhanced basal-level ABA responses. Epidermal salt bladder cells exhibit similar characteristics as trichomes, with a significantly higher expression of genes related to energy import and ABA biosynthesis compared with the leaf lamina. The quinoa genome sequence provides insights into its exceptional nutritional value and the evolution of halophytes, enabling the identification of genes involved in salinity tolerance, and providing the basis for molecular breeding in quinoa. PMID:28994416

  16. New Paradigms for the Study of Ocular Alphaherpesvirus Infections: Insights into the Use of Non-Traditional Host Model Systems

    Directory of Open Access Journals (Sweden)

    Matthew R. Pennington

    2017-11-01

    Full Text Available Ocular herpesviruses, most notably human alphaherpesvirus 1 (HSV-1, canid alphaherpesvirus 1 (CHV-1 and felid alphaherpesvirus 1 (FHV-1, infect and cause severe disease that may lead to blindness. CHV-1 and FHV-1 have a pathogenesis and induce clinical disease in their hosts that is similar to HSV-1 ocular infections in humans, suggesting that infection of dogs and cats with CHV-1 and FHV-1, respectively, can be used as a comparative natural host model of herpesvirus-induced ocular disease. In this review, we discuss both strengths and limitations of the various available model systems to study ocular herpesvirus infection, with a focus on the use of these non-traditional virus-natural host models. Recent work has demonstrated the robustness and reproducibility of experimental ocular herpesvirus infections in dogs and cats, and, therefore, these non-traditional models can provide additional insights into the pathogenesis of ocular herpesvirus infections.

  17. Underperformance of African protected area networks and the case for new conservation models: insights from Zambia.

    Science.gov (United States)

    Lindsey, Peter A; Nyirenda, Vincent R; Barnes, Jonathan I; Becker, Matthew S; McRobb, Rachel; Tambling, Craig J; Taylor, W Andrew; Watson, Frederick G; t'Sas-Rolfes, Michael

    2014-01-01

    Many African protected areas (PAs) are not functioning effectively. We reviewed the performance of Zambia's PA network and provide insights into how their effectiveness might be improved. Zambia's PAs are under-performing in ecological, economic and social terms. Reasons include: a) rapidly expanding human populations, poverty and open-access systems in Game Management Areas (GMAs) resulting in widespread bushmeat poaching and habitat encroachment; b) underfunding of the Zambia Wildlife Authority (ZAWA) resulting in inadequate law enforcement; c) reliance of ZAWA on extracting revenues from GMAs to cover operational costs which has prevented proper devolution of user-rights over wildlife to communities; d) on-going marginalization of communities from legal benefits from wildlife; e) under-development of the photo-tourism industry with the effect that earnings are limited to a fraction of the PA network; f) unfavourable terms and corruption which discourage good practice and adequate investment by hunting operators in GMAs; g) blurred responsibilities regarding anti-poaching in GMAs resulting in under-investment by all stakeholders. The combined effect of these challenges has been a major reduction in wildlife densities in most PAs and the loss of habitat in GMAs. Wildlife fares better in areas with investment from the private and/or NGO sector and where human settlement is absent. There is a need for: elevated government funding for ZAWA; greater international donor investment in protected area management; a shift in the role of ZAWA such that they focus primarily on national parks while facilitating the development of wildlife-based land uses by other stakeholders elsewhere; and new models for the functioning of GMAs based on joint-ventures between communities and the private and/or NGO sector. Such joint-ventures should provide defined communities with ownership of land, user-rights over wildlife and aim to attract long-term private/donor investment. These

  18. What's statistical about learning? Insights from modelling statistical learning as a set of memory processes.

    Science.gov (United States)

    Thiessen, Erik D

    2017-01-05

    Statistical learning has been studied in a variety of different tasks, including word segmentation, object identification, category learning, artificial grammar learning and serial reaction time tasks (e.g. Saffran et al. 1996 Science 274: , 1926-1928; Orban et al. 2008 Proceedings of the National Academy of Sciences 105: , 2745-2750; Thiessen & Yee 2010 Child Development 81: , 1287-1303; Saffran 2002 Journal of Memory and Language 47: , 172-196; Misyak & Christiansen 2012 Language Learning 62: , 302-331). The difference among these tasks raises questions about whether they all depend on the same kinds of underlying processes and computations, or whether they are tapping into different underlying mechanisms. Prior theoretical approaches to statistical learning have often tried to explain or model learning in a single task. However, in many cases these approaches appear inadequate to explain performance in multiple tasks. For example, explaining word segmentation via the computation of sequential statistics (such as transitional probability) provides little insight into the nature of sensitivity to regularities among simultaneously presented features. In this article, we will present a formal computational approach that we believe is a good candidate to provide a unifying framework to explore and explain learning in a wide variety of statistical learning tasks. This framework suggests that statistical learning arises from a set of processes that are inherent in memory systems, including activation, interference, integration of information and forgetting (e.g. Perruchet & Vinter 1998 Journal of Memory and Language 39: , 246-263; Thiessen et al. 2013 Psychological Bulletin 139: , 792-814). From this perspective, statistical learning does not involve explicit computation of statistics, but rather the extraction of elements of the input into memory traces, and subsequent integration across those memory traces that emphasize consistent information (Thiessen and Pavlik

  19. A comprehensive comparison of four species of Onchidiidae provides insights on the morphological and molecular adaptations of invertebrates from shallow seas to wetlands

    Science.gov (United States)

    Wang, Dongfeng; Li, Jie; Liu, Xin; Wu, Xin

    2018-01-01

    The Onchidiidae family is ideal for studying the evolution of marine invertebrate species from sea to wetland environments. However, comparative studies of Onchidiidae species are rare. A total of 40 samples were collected from four species (10 specimens per onchidiid), and their histological and molecular differences were systematically evaluated to elucidate the morphological foundations underlying the adaptations of these species. A histological analysis was performed to compare the structures of respiratory organs (gill, lung sac, dorsal skin) among onchidiids, and transcriptome sequencing of four representative onchidiids was performed to investigate the molecular mechanisms associated with their respective habitats. Twenty-six SNP markers of Onchidium reevesii revealed some DNA polymorphisms determining visible traits. Non-muscle myosin heavy chain II (NMHC II) and myosin heavy chain (MyHC), which play essential roles in amphibian developmental processes, were found to be differentially expressed in different onchidiids and tissues. The species with higher terrestrial ability and increased integrated expression of Os-MHC (NMHC II gene) and the MyHC gene, illustrating that the expression levels of these genes were associated with the evolutionary degree. This study provides a comprehensive analysis of the adaptions of a diverse and widespread group of invertebrates, the Onchidiidae. Some onchidiids can breathe well through gills and skin when under seawater, and some can breathe well through lung sacs and skin when in wetlands. A histological comparison of respiratory organs and the relative expression levels of two genes provided insights into the adaptions of onchidiids that allowed their transition from shallow seas to wetlands. This work provides a valuable reference and might encourage further study. PMID:29698429

  20. iTRAQ and RNA-Seq Analyses Provide New Insights into Regulation Mechanism of Symbiotic Germination of Dendrobium officinale Seeds (Orchidaceae).

    Science.gov (United States)

    Chen, Juan; Liu, Si Si; Kohler, Annegret; Yan, Bo; Luo, Hong Mei; Chen, Xiao Mei; Guo, Shun Xing

    2017-06-02

    Mycorrhizal fungi colonize orchid seeds and induce germination. This so-called symbiotic germination is a critical developmental process in the lifecycle of all orchid species. However, the molecular changes that occur during orchid seed symbiotic germination remain largely unknown. To better understand the molecular mechanism of orchid seed germination, we performed a comparative transcriptomic and proteomic analysis of the Chinese traditional medicinal orchid Dendrobium officinale to explore the change in protein expression at the different developmental stages during asymbiotic and symbiotic germination and identify the key proteins that regulate the symbiotic germination of orchid seeds. Among 2256 identified plant proteins, 308 were differentially expressed across three developmental stages during asymbiotic and symbiotic germination, and 229 were differentially expressed during symbiotic germination compared to asymbiotic development. Of these, 32 proteins were coup-regulated at both the proteomic and transcriptomic levels during symbiotic germination compared to asymbiotic germination. Our results suggest that symbiotic germination of D. officinale seeds shares a common signaling pathway with asymbiotic germination during the early germination stage. However, compared to asymbiotic germination, fungal colonization of orchid seeds appears to induce higher and earlier expression of some key proteins involved in lipid and carbohydrate metabolism and thus improves the efficiency of utilization of stored substances present in the embryo. This study provides new insight into the molecular basis of orchid seed germination.

  1. Ninety-nine de novo assembled genomes from the moose (Alces alces) rumen microbiome provide new insights into microbial plant biomass degradation

    Science.gov (United States)

    Svartström, Olov; Alneberg, Johannes; Terrapon, Nicolas; Lombard, Vincent; de Bruijn, Ino; Malmsten, Jonas; Dalin, Ann-Marie; Muller, Emilie E.L.; Shah, Pranjul; Wilmes, Paul; Henrissat, Bernard; Aspeborg, Henrik; Andersson, Anders F.

    2017-01-01

    The moose (Alces alces) is a ruminant that harvests energy from fiber-rich lignocellulose material through carbohydrate-active enzymes (CAZymes) produced by its rumen microbes. We applied shotgun metagenomics to rumen contents from six moose to obtain insights into this microbiome. Following binning, 99 metagenome-assembled genomes (MAGs) belonging to eleven prokaryotic phyla were reconstructed and characterized based on phylogeny and CAZyme profile. The taxonomy of these MAGs reflected the overall composition of the metagenome, with dominance of the phyla Bacteroidetes and Firmicutes. Unlike in other ruminants, Spirochaetes constituted a significant proportion of the community and our analyses indicate that the corresponding strains are primarily pectin digesters. Pectin-degrading genes were also common in MAGs of Ruminococcus, Fibrobacteres and Bacteroidetes, and were overall overrepresented in the moose microbiome compared to other ruminants. Phylogenomic analyses revealed several clades within the Bacteriodetes without previously characterized genomes. Several of these MAGs encoded a large numbers of dockerins, a module usually associated with cellulosomes. The Bacteroidetes dockerins were often linked to CAZymes and sometimes encoded inside polysaccharide utilization loci (PULs), which has never been reported before. The almost one hundred CAZyme-annotated genomes reconstructed in this study provides an in-depth view of an efficient lignocellulose-degrading microbiome and prospects for developing enzyme technology for biorefineries. PMID:28731473

  2. Whole genome sequencing of a banana wild relative Musa itinerans provides insights into lineage-specific diversification of the Musa genus.

    Science.gov (United States)

    Wu, Wei; Yang, Yu-Lan; He, Wei-Ming; Rouard, Mathieu; Li, Wei-Ming; Xu, Meng; Roux, Nicolas; Ge, Xue-Jun

    2016-08-17

    Crop wild relatives are valuable resources for future genetic improvement. Here, we report the de novo genome assembly of Musa itinerans, a disease-resistant wild banana relative in subtropical China. The assembled genome size was 462.1 Mb, covering 75.2% of the genome (615.2Mb) and containing 32, 456 predicted protein-coding genes. Since the approximate divergence around 5.8 million years ago, the genomes of Musa itinerans and Musa acuminata have shown conserved collinearity. Gene family expansions and contractions enrichment analysis revealed that some pathways were associated with phenotypic or physiological innovations. These include a transition from wood to herbaceous in the ancestral Musaceae, intensification of cold and drought tolerances, and reduced diseases resistance genes for subtropical marginally distributed Musa species. Prevalent purifying selection and transposed duplications were found to facilitate the diversification of NBS-encoding gene families for two Musa species. The population genome history analysis of M. itinerans revealed that the fluctuated population sizes were caused by the Pleistocene climate oscillations, and that the formation of Qiongzhou Strait might facilitate the population downsizing on the isolated Hainan Island about 10.3 Kya. The qualified assembly of the M. itinerans genome provides deep insights into the lineage-specific diversification and also valuable resources for future banana breeding.

  3. Deletion of thyrotropin receptor residue Asp403 in a hyperfunctioning thyroid nodule provides insight into the role of the ectodomain in ligand-induced receptor activation.

    Science.gov (United States)

    Nishihara, E; Chen, C-R; Mizutori-Sasai, Y; Ito, M; Kubota, S; Amino, N; Miyauchi, A; Rapoport, B

    2012-01-01

    Somatic mutations of the TSH receptor (TSHR) gene are the main cause of autonomously functioning thyroid nodules. Except for mutations in ectodomain residue S281, all of the numerous reported activating mutations are in the TSHR membrane-spanning region. Here, we describe a patient with a toxic adenoma with a novel heterozygous somatic mutation caused by deletion of ectodomain residue Asp403 (Del-D403). Subsequent in vitro functional studies of the Del-D403 TSHR mutation demonstrated greatly increased ligand-independent constitutive activity, 8-fold above that of the wild-type TSHR. TSH stimulation had little further effect, indicating that the mutation produced near maximal activation of the receptor. In summary, we report only the second TSHR ectodomain activating mutation (and the first ectodomain deletion mutation) responsible for development of a thyroid toxic adenoma. Because Del-D403 causes near maximal activation, our finding provides novel insight into TSHR structure and function; residue D403 is more likely to be involved in the ligand-mediated activating pathway than in the ectodomain inverse agonist property.

  4. Using economic instruments to develop effective management of invasive species: insights from a bioeconomic model.

    Science.gov (United States)

    McDermott, Shana M; Irwin, Rebecca E; Taylor, Brad W

    2013-07-01

    critical. To accomplish the management and enforcement of these economic policies, we discuss modification of existing agencies and infrastructure. Finally, a sensitivity analysis revealed that lowering the economic cost of invader removal would strongly increase the probability of invader eradication. Taken together, our results provide quantitative insight into management decisions and economic policy instruments that can encourage invasive species removal across a social landscape.

  5. Multi-Layered Stratification in the Baltic Sea: Insight from a Modeling Study with Reference to Environmental Conditions

    Directory of Open Access Journals (Sweden)

    Bijan Dargahi

    2017-01-01

    Full Text Available The hydrodynamic and transport characteristics of the Baltic Sea in the period 2000–2009 were studied using a fully calibrated and validated 3D hydrodynamic model with a horizontal resolution of 4.8 km. This study provided new insight into the type and dynamics of vertical structure in the Baltic Sea, not considered in previous studies. Thermal and salinity stratification are both addressed, with a focus on the structural properties of the layers. The detection of cooler regions (dicothermal within the layer structure is an important finding. The detailed investigation of thermal stratification for a 10-year period (i.e., 2000–2009 revealed some new features. A multilayered structure that contains several thermocline and dicothermal layers was identified from this study. Statistical analysis of the simulation results made it possible to derive the mean thermal stratification properties, expressed as mean temperatures and the normalized layer thicknesses. The three-layered model proposed by previous investigators appears to be valid only during the winter periods; for other periods, a multi-layered structure with more than five layers has been identified during this investigation. This study provides detailed insight into thermal and salinity stratification in the Baltic Sea during a recent decade that can be used as a basis for diverse environmental assessments. It extends previous studies on stratification in the Baltic Sea regarding both the extent and the nature of stratification.

  6. Insight into the relationship between impulsivity and substance abuse from studies using animal models.

    Science.gov (United States)

    Winstanley, Catharine A; Olausson, Peter; Taylor, Jane R; Jentsch, J David

    2010-08-01

    Drug use disorders are often accompanied by deficits in the capacity to efficiently process reward-related information and to monitor, suppress, or override reward-controlled behavior when goals are in conflict with aversive or immediate outcomes. This emerging deficit in behavioral flexibility and impulse control may be a central component of the progression to addiction, as behavior becomes increasingly driven by drugs and drug-associated cues at the expense of more advantageous activities. Understanding how neural mechanisms implicated in impulse control are affected by addictive drugs may therefore prove a useful strategy in the search for new treatment options. Animal models of impulsivity and addiction could make a significant contribution to this endeavor. Here, some of the more common behavioral paradigms used to measure different aspects of impulsivity across species are outlined, and the importance of the response to reward-paired cues in such paradigms is discussed. Naturally occurring differences in forms of impulsivity have been found to be predictive of future drug self-administration, but drug exposure can also increase impulsive responding. Such data are in keeping with the suggestion that impulsivity may contribute to multiple stages within the spiral of addiction. From a neurobiological perspective, converging evidence from rat, monkey, and human studies suggest that compromised functioning within the orbitofrontal cortex may critically contribute to the cognitive sequelae of drug abuse. Changes in gene transcription and protein expression within this region may provide insight into the mechanism underlying drug-induced cortical hypofunction, reflecting new molecular targets for the treatment of uncontrolled drug-seeking and drug-taking behavior.

  7. Dilution of 10Be in detrital quartz by earthquake-induced landslides: Implications for determining denudation rates and potential to provide insights into landslide sediment dynamics

    Science.gov (United States)

    West, A. Joshua; Hetzel, Ralf; Li, Gen; Jin, Zhangdong; Zhang, Fei; Hilton, Robert G.; Densmore, Alexander L.

    2014-06-01

    hydrological gauging, respectively. Such information could provide new insight into sediment transfer, with implications for secondary sediment-related hazards and for understanding the removal of mass from mountains.

  8. Transcriptome analysis of skin fibroblasts with dominant negative COL3A1 mutations provides molecular insights into the etiopathology of vascular Ehlers-Danlos syndrome.

    Science.gov (United States)

    Chiarelli, Nicola; Carini, Giulia; Zoppi, Nicoletta; Ritelli, Marco; Colombi, Marina

    2018-01-01

    Vascular Ehlers-Danlos syndrome (vEDS) is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII), which is the major expressed collagen in blood vessels and hollow organs. The majority of disease-causing variants in COL3A1 are glycine substitutions and in-frame splice mutations in the triple helix domain that through a dominant negative effect are associated with the severe clinical spectrum potentially lethal of vEDS, characterized by fragility of soft connective tissues with arterial and organ ruptures. To shed lights into molecular mechanisms underlying vEDS, we performed gene expression profiling in cultured skin fibroblasts from three patients with different structural COL3A1 mutations. Transcriptome analysis revealed significant changes in the expression levels of several genes involved in maintenance of cell redox and endoplasmic reticulum (ER) homeostasis, COLLs folding and extracellular matrix (ECM) organization, formation of the proteasome complex, and cell cycle regulation. Protein analyses showed that aberrant COLLIII expression is associated with the disassembly of many structural ECM constituents, such as fibrillins, EMILINs, and elastin, as well as with the reduction of the proteoglycans perlecan, decorin, and versican, all playing an important role in the vascular system. Furthermore, the altered distribution of the ER marker protein disulfide isomerase PDI and the strong reduction of the COLLs-modifying enzyme FKBP22 are consistent with the disturbance of ER-related homeostasis and COLLs biosynthesis and post-translational modifications, indicated by microarray analysis. Our findings add new insights into the pathophysiology of this severe vascular disorder, since they provide a picture of the gene expression changes in vEDS skin fibroblasts and highlight that dominant negative mutations in COL3A1 also affect post-translational modifications and deposition into the ECM of

  9. Transcriptome analysis of skin fibroblasts with dominant negative COL3A1 mutations provides molecular insights into the etiopathology of vascular Ehlers-Danlos syndrome.

    Directory of Open Access Journals (Sweden)

    Nicola Chiarelli

    Full Text Available Vascular Ehlers-Danlos syndrome (vEDS is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII, which is the major expressed collagen in blood vessels and hollow organs. The majority of disease-causing variants in COL3A1 are glycine substitutions and in-frame splice mutations in the triple helix domain that through a dominant negative effect are associated with the severe clinical spectrum potentially lethal of vEDS, characterized by fragility of soft connective tissues with arterial and organ ruptures. To shed lights into molecular mechanisms underlying vEDS, we performed gene expression profiling in cultured skin fibroblasts from three patients with different structural COL3A1 mutations. Transcriptome analysis revealed significant changes in the expression levels of several genes involved in maintenance of cell redox and endoplasmic reticulum (ER homeostasis, COLLs folding and extracellular matrix (ECM organization, formation of the proteasome complex, and cell cycle regulation. Protein analyses showed that aberrant COLLIII expression is associated with the disassembly of many structural ECM constituents, such as fibrillins, EMILINs, and elastin, as well as with the reduction of the proteoglycans perlecan, decorin, and versican, all playing an important role in the vascular system. Furthermore, the altered distribution of the ER marker protein disulfide isomerase PDI and the strong reduction of the COLLs-modifying enzyme FKBP22 are consistent with the disturbance of ER-related homeostasis and COLLs biosynthesis and post-translational modifications, indicated by microarray analysis. Our findings add new insights into the pathophysiology of this severe vascular disorder, since they provide a picture of the gene expression changes in vEDS skin fibroblasts and highlight that dominant negative mutations in COL3A1 also affect post-translational modifications and deposition

  10. Investigation of bacterial communities within the digestive organs of the hydrothermal vent shrimp Rimicaris exoculata provide insights into holobiont geographic clustering.

    Directory of Open Access Journals (Sweden)

    Dominique A Cowart

    Full Text Available Prokaryotic communities forming symbiotic relationships with the vent shrimp, Rimicaris exoculata, are well studied components of hydrothermal ecosystems at the Mid-Atlantic Ridge (MAR. Despite the tight link between host and symbiont, the observed lack of spatial genetic structure seen in R. exoculata contrasts with the geographic differentiation detected in specific bacterial ectosymbionts. The geographic clustering of bacterial lineages within a seemingly panmictic host suggests either the presence of finer scale restriction to gene flow not yet detected in the host, horizontal transmission (environmental selection of its endosymbionts as a consequence of unique vent geochemistry, or vertically transmitted endosymbionts that exhibit genetic differentiation. To identify which hypothesis best fits, we tested whether bacterial assemblages exhibit differentiation across sites or host populations by performing a 16S rRNA metabarcoding survey on R. exoculata digestive prokaryote samples (n = 31 taken from three geochemically distinct vents across MAR: Rainbow, Trans-Atlantic Geotraverse (TAG and Logatchev. Analysis of communities across two organs (digestive tract, stomach, three molt colors (white, red, black and three life stages (eggs, juveniles, adults also provided insights into symbiont transmission mode. Examining both whole communities and operational taxonomic units (OTUs confirmed the presence of three main epibionts: Epsilonproteobacteria, Mollicutes and Deferribacteres. With these findings, we identified a clear pattern of geographic segregation by vent in OTUs assigned to Epsilonproteobacteria. Additionally, we detected evidence for differentiation among all communities associated to vents and life stages. Overall, results suggest a combination of environmental selection and vertical inheritance of some of the symbiotic lineages.

  11. Expression and phylogenetic analyses of the Gel/Gas proteins of Tuber melanosporum provide insights into the function and evolution of glucan remodeling enzymes in fungi.

    Science.gov (United States)

    Sillo, Fabiano; Gissi, Carmela; Chignoli, Daniele; Ragni, Enrico; Popolo, Laura; Balestrini, Raffaella

    2013-04-01

    The β(1,3)-glucanosyltransferases of the GH72 family are redundant enzymes that are essential for the formation and dynamic remodeling of the fungal wall during different stages of the life cycle. Four putative genes encoding glycosylphosphatidylinositol (GPI)-anchored β(1,3)-glucanosyltransferases, designated TmelGEL1, TmelGEL2, TmelGEL4 and TmelGAS4, have been annotated in the genome of Tuber melanosporum, an ectomycorrhizal fungus that also produces a hypogeous fruiting body (FB) of great commercial value (black truffle). This work focuses on the characterization and expression of this multigene family by taking advantage of a laser microdissection (LMD) technology that has been used to separate two distinct compartments in the FB, the hyphae and the asci containing the ascospores. Of the four genes, TmelGEL1 was the most up-regulated in the FB compared to the free-living mycelium. Inside the FB, the expression of TmelGEL1 was restricted to the hyphal compartment. A phylogenetic analysis of the Gel/Gas protein family of T. melanosporum was also carried out. A total of 237 GH72 proteins from 51 Ascomycotina and 3 Basidiomycota (outgroup) species were analyzed. The resulting tree provides insight into the evolution of the T. melanosporum proteins and identifies new GH72 paralogs/subfamilies. Moreover, it represents a starting point to formulate new hypotheses on the significance of the striking GH72 gene redundancy in fungal biology. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Yeast Interspecies Comparative Proteomics Reveals Divergence in Expression Profiles and Provides Insights into Proteome Resource Allocation and Evolutionary Roles of Gene Duplication*

    Science.gov (United States)

    Kito, Keiji; Ito, Haruka; Nohara, Takehiro; Ohnishi, Mihoko; Ishibashi, Yuko; Takeda, Daisuke

    2016-01-01

    nonoptimal culture conditions but also provide valuable insights into intriguing biological principles, including the balance of proteome resource allocation and the role of gene duplication in evolutionary history. PMID:26560065

  13. A Rickettsia Genome Overrun by Mobile Genetic Elements Provides Insight into the Acquisition of Genes Characteristic of an Obligate Intracellular Lifestyle

    Science.gov (United States)

    Joardar, Vinita; Williams, Kelly P.; Driscoll, Timothy; Hostetler, Jessica B.; Nordberg, Eric; Shukla, Maulik; Walenz, Brian; Hill, Catherine A.; Nene, Vishvanath M.; Azad, Abdu F.; Sobral, Bruno W.; Caler, Elisabet

    2012-01-01

    We present the draft genome for the Rickettsia endosymbiont of Ixodes scapularis (REIS), a symbiont of the deer tick vector of Lyme disease in North America. Among Rickettsia species (Alphaproteobacteria: Rickettsiales), REIS has the largest genome sequenced to date (>2 Mb) and contains 2,309 genes across the chromosome and four plasmids (pREIS1 to pREIS4). The most remarkable finding within the REIS genome is the extraordinary proliferation of mobile genetic elements (MGEs), which contributes to a limited synteny with other Rickettsia genomes. In particular, an integrative conjugative element named RAGE (for Rickettsiales amplified genetic element), previously identified in scrub typhus rickettsiae (Orientia tsutsugamushi) genomes, is present on both the REIS chromosome and plasmids. Unlike the pseudogene-laden RAGEs of O. tsutsugamushi, REIS encodes nine conserved RAGEs that include F-like type IV secretion systems similar to that of the tra genes encoded in the Rickettsia bellii and R. massiliae genomes. An unparalleled abundance of encoded transposases (>650) relative to genome size, together with the RAGEs and other MGEs, comprise ∼35% of the total genome, making REIS one of the most plastic and repetitive bacterial genomes sequenced to date. We present evidence that conserved rickettsial genes associated with an intracellular lifestyle were acquired via MGEs, especially the RAGE, through a continuum of genomic invasions. Robust phylogeny estimation suggests REIS is ancestral to the virulent spotted fever group of rickettsiae. As REIS is not known to invade vertebrate cells and has no known pathogenic effects on I. scapularis, its genome sequence provides insight on the origin of mechanisms of rickettsial pathogenicity. PMID:22056929

  14. Plantation forestry under global warming: hybrid poplars with improved thermotolerance provide new insights on the in vivo function of small heat shock protein chaperones.

    Science.gov (United States)

    Merino, Irene; Contreras, Angela; Jing, Zhong-Ping; Gallardo, Fernando; Cánovas, Francisco M; Gómez, Luis

    2014-02-01

    Climate-driven heat stress is a key factor affecting forest plantation yields. While its effects are expected to worsen during this century, breeding more tolerant genotypes has proven elusive. We report here a substantial and durable increase in the thermotolerance of hybrid poplar (Populus tremula×Populus alba) through overexpression of a major small heat shock protein (sHSP) with convenient features. Experimental evidence was obtained linking protective effects in the transgenic events with the unique chaperone activity of sHSPs. In addition, significant positive correlations were observed between phenotype strength and heterologous sHSP accumulation. The remarkable baseline levels of transgene product (up to 1.8% of total leaf protein) have not been reported in analogous studies with herbaceous species. As judged by protein analyses, such an accumulation is not matched either by endogenous sHSPs in both heat-stressed poplar plants and field-grown adult trees. Quantitative real time-polymerase chain reaction analyses supported these observations and allowed us to identify the poplar members most responsive to heat stress. Interestingly, sHSP overaccumulation was not associated with pleiotropic effects that might decrease yields. The poplar lines developed here also outperformed controls under in vitro and ex vitro culture conditions (callus biomass, shoot production, and ex vitro survival), even in the absence of thermal stress. These results reinforce the feasibility of improving valuable genotypes for plantation forestry, a field where in vitro recalcitrance, long breeding cycles, and other practical factors constrain conventional genetic approaches. They also provide new insights into the biological functions of the least understood family of heat shock protein chaperones.

  15. Transcriptome-based gene profiling provides novel insights into the characteristics of radish root response to Cr stress with next-generation sequencing

    Directory of Open Access Journals (Sweden)

    Yang eXie

    2015-03-01

    Full Text Available Radish (Raphanus sativus L. is an important worldwide root vegetable crop with high nutrient values and is adversely affected by non-essential heavy metals including chromium (Cr. Little is known about the molecular mechanism underlying Cr stress response in radish. In this study, RNA-Seq technique was employed to identify differentially expressed genes (DEGs under Cr stress. Based on de novo transcriptome assembly, there were 30,676 unigenes representing 60,881 transcripts isolated from radish root under Cr stress. Differential gene analysis revealed that 2,985 uingenes were significantly differentially expressed between Cr-free (CK and Cr-treated (Cr600 libraries, among which 1,424 were up-regulated and 1,561 down-regulated. Gene ontology (GO analysis revealed that these DEGs were mainly involved in primary metabolic process, response to abiotic stimulus, cellular metabolic process and small molecule metabolic process. Kyoto encyclopedia of genes and genomes (KEGG enrichment analysis showed that the DEGs were mainly involved in protein processing in endoplasmic reticulum, starch and sucrose metabolism, amino acid metabolism, glutathione metabolism, drug and xenobiotics by cytochrome P450 metabolism. RT-qPCR analysis showed that the expression patterns of 12 randomly selected DEGs were highly accordant with the results from RNA-seq. Furthermore, many candidate genes including signaling protein kinases, transcription factors and metal transporters, chelate compound biosynthesis and antioxidant system, were involved in defense and detoxification mechanisms of Cr stress response regulatory networks. These results would provide novel insight into molecular mechanism underlying plant responsiveness to Cr stress and facilitate further genetic manipulation on Cr uptake and accumulation in radish.

  16. Analysis of DNA binding by human factor xeroderma pigmentosum complementation group A (XPA) provides insight into its interactions with nucleotide excision repair substrates.

    Science.gov (United States)

    Sugitani, Norie; Voehler, Markus W; Roh, Michelle S; Topolska-Woś, Agnieszka M; Chazin, Walter J

    2017-10-13

    Xeroderma pigmentosum (XP) complementation group A (XPA) is an essential scaffolding protein in the multiprotein nucleotide excision repair (NER) machinery. The interaction of XPA with DNA is a core function of this protein; a number of mutations in the DNA-binding domain (DBD) are associated with XP disease. Although structures of the central globular domain of human XPA and data on binding of DNA substrates have been reported, the structural basis for XPA's DNA-binding activity remains unknown. X-ray crystal structures of the central globular domain of yeast XPA (Rad14) with lesion-containing DNA duplexes have provided valuable insights, but the DNA substrates used for this study do not correspond to the substrates of XPA as it functions within the NER machinery. To better understand the DNA-binding activity of human XPA in NER, we used NMR to investigate the interaction of its DBD with a range of DNA substrates. We found that XPA binds different single-stranded/double-stranded junction DNA substrates with a common surface. Comparisons of our NMR-based mapping of binding residues with the previously reported Rad14-DNA crystal structures revealed similarities and differences in substrate binding between XPA and Rad14. This includes direct evidence for DNA contacts to the residues extending C-terminally from the globular core, which are lacking in the Rad14 construct. Moreover, mutation of the XPA residue corresponding to Phe-262 in Rad14, previously reported as being critical for DNA binding, had only a moderate effect on the DNA-binding activity of XPA. The DNA-binding properties of several disease-associated mutations in the DBD were investigated. These results suggest that for XPA mutants exhibiting altered DNA-binding properties, a correlation exists between the extent of reduction in DNA-binding affinity and the severity of symptoms in XP patients. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Conventional and phenomics characterization provides insight into the diversity and relationships of hypervariable scarlet (Solanum aethiopicum L. and gboma (S. macrocarpon L. eggplant complexes

    Directory of Open Access Journals (Sweden)

    Mariola ePlazas

    2014-07-01

    Full Text Available Scarlet (Solanum aethiopicum and gboma (S. macrocarpon eggplants are major vegetable crops in sub-Saharan Africa. Together with their respective wild ancestors (S. anguivi and S. dasyphyllum and intermediate cultivated-wild forms they constitute the so-called scarlet and gboma eggplant complexes. We used conventional descriptors and the high-throughput phenomics tool Tomato Analyzer for characterizing 63 accessions of the scarlet eggplant complex, including the four S. aethiopicum cultivar groups (Aculeatum, Gilo, Kumba, and Shum, Intermediate S. aethiopicum-S. anguivi forms, and S. anguivi, and 12 cultivated and wild accessions of the gboma eggplant complex. A large diversity was found between both complexes, showing that they are very well differentiated from each other. Within the scarlet eggplant complex, many significant differences were also found among cultivar groups, but more differences were found for fruit traits evaluated with Tomato Analyzer than with conventional descriptors. In particular, Tomato Analyzer phenomics characterization was useful for distinguishing small fruited groups (Shum, Intermediate, and S. anguivi, as well as groups for which few or no significant differences were observed for plant traits. Multivariate principal components analysis (PCA separated well all groups, except the Intermediate group which plotted between S. anguivi and small fruited S. aethiopicum accessions. For the gboma eggplant complex, S. dasyphyllum was clearly distinguished from S. macrocarpon and an important diversity was found in the latter. The results have shown that both complexes are hypervariable and have provided insight into their diversity and relationships. The information obtained has important implications for the conservation and management of genetic resources as well as for the selection and breeding of both scarlet and gboma eggplants.

  18. Organization of left–right coordination of neuronal activity in the mammalian spinal cord: Insights from computational modelling

    Science.gov (United States)

    Shevtsova, Natalia A; Talpalar, Adolfo E; Markin, Sergey N; Harris-Warrick, Ronald M; Kiehn, Ole; Rybak, Ilya A

    2015-01-01

    Different locomotor gaits in mammals, such as walking or galloping, are produced by coordinated activity in neuronal circuits in the spinal cord. Coordination of neuronal activity between left and right sides of the cord is provided by commissural interneurons (CINs), whose axons cross the midline. In this study, we construct and analyse two computational models of spinal locomotor circuits consisting of left and right rhythm generators interacting bilaterally via several neuronal pathways mediated by different CINs. The CIN populations incorporated in the models include the genetically identified inhibitory (V0D) and excitatory (V0V) subtypes of V0 CINs and excitatory V3 CINs. The model also includes the ipsilaterally projecting excitatory V2a interneurons mediating excitatory drive to the V0V CINs. The proposed network architectures and CIN connectivity allow the models to closely reproduce and suggest mechanistic explanations for several experimental observations. These phenomena include: different speed-dependent contributions of V0D and V0V CINs and V2a interneurons to left–right alternation of neural activity, switching gaits between the left–right alternating walking-like activity and the left–right synchronous hopping-like pattern in mutants lacking specific neuron classes, and speed-dependent asymmetric changes of flexor and extensor phase durations. The models provide insights into the architecture of spinal network and the organization of parallel inhibitory and excitatory CIN pathways and suggest explanations for how these pathways maintain alternating and synchronous gaits at different locomotor speeds. The models propose testable predictions about the neural organization and operation of mammalian locomotor circuits. Key points Coordination of neuronal activity between left and right sides of the mammalian spinal cord is provided by several sets of commissural interneurons (CINs) whose axons cross the midline. Genetically identified inhibitory V

  19. Tectonic drivers of the Wrangell block: Insights on fore-arc sliver processes from 3-D geodynamic models of Alaska

    Science.gov (United States)

    Haynie, K. L.; Jadamec, M. A.

    2017-07-01

    Intracontinental shear zones can play a key role in understanding how plate convergence is manifested in the upper plate in regions of oblique subduction. However, the relative role of the driving forces from the subducting plate and the resisting force from within intracontinental shear zones is not well understood. Results from high-resolution, geographically referenced, instantaneous 3-D geodynamic models of flat slab subduction at the oblique convergent margin of Alaska are presented. These models investigate how viscosity and length of the Denali fault intracontinental shear zone as well as coupling along the plate boundary interface modulate motion of the Wrangell block fore-arc sliver and slip across the Denali fault. Models with a weak Denali fault (1017 Pa s) and strong plate coupling (1021 Pa s) were found to produce the fastest motions of the Wrangell block (˜10 mm/yr). The 3-D models predict along-strike variation in motion along the Denali fault, changing from dextral strike-slip motion in the eastern segment to oblique convergence toward the fault apex. Models further show that the flat slab drives oblique motion of the Wrangell block and contributes to 20% (models with a short fault) and 28% (models with a long fault) of the observed Quaternary slip rates along the Denali fault. The 3-D models provide insight into the general processes of fore-arc sliver mechanics and also offer a 3-D framework for interpreting hazards in regions of flat slab subduction.

  20. Integrated RNA- and protein profiling of fermentation and respiration in diploid budding yeast provides insight into nutrient control of cell growth and development.

    Science.gov (United States)

    Becker, Emmanuelle; Liu, Yuchen; Lardenois, Aurélie; Walther, Thomas; Horecka, Joe; Stuparevic, Igor; Law, Michael J; Lavigne, Régis; Evrard, Bertrand; Demougin, Philippe; Riffle, Michael; Strich, Randy; Davis, Ronald W; Pineau, Charles; Primig, Michael

    2015-04-24

    Diploid budding yeast undergoes rapid mitosis when it ferments glucose, and in the presence of a non-fermentable carbon source and the absence of a nitrogen source it triggers sporulation. Rich medium with acetate is a commonly used pre-sporulation medium, but our understanding of the molecular events underlying the acetate-driven transition from mitosis to meiosis is still incomplete. We identified 263 proteins for which mRNA and protein synthesis are linked or uncoupled in fermenting and respiring cells. Using motif predictions, interaction data and RNA profiling we find among them 28 likely targets for Ume6, a subunit of the conserved Rpd3/Sin3 histone deacetylase-complex regulating genes involved in metabolism, stress response and meiosis. Finally, we identify 14 genes for which both RNA and proteins are detected exclusively in respiring cells but not in fermenting cells in our sample set, including CSM4, SPR1, SPS4 and RIM4, which were thought to be meiosis-specific. Our work reveals intertwined transcriptional and post-transcriptional control mechanisms acting when a MATa/α strain responds to nutritional signals, and provides molecular clues how the carbon source primes yeast cells for entering meiosis. Our integrated genomics study provides insight into the interplay between the transcriptome and the proteome in diploid yeast cells undergoing vegetative growth in the presence of glucose (fermentation) or acetate (respiration). Furthermore, it reveals novel target genes involved in these processes for Ume6, the DNA binding subunit of the conserved histone deacetylase Rpd3 and the co-repressor Sin3. We have combined data from an RNA profiling experiment using tiling arrays that cover the entire yeast genome, and a large-scale protein detection analysis based on mass spectrometry in diploid MATa/α cells. This distinguishes our study from most others in the field-which investigate haploid yeast strains-because only diploid cells can undergo meiotic development