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Sample records for biologically relevant metal-based

  1. Making Plant Biology Curricula Relevant.

    ERIC Educational Resources Information Center

    Hershey, David R.

    1992-01-01

    Reviews rationale, purposes, challenges, and relevance of hands-on, plant biology curricula that have been developed in response to the limited use of plants in biology education. Discusses methods to maintain both instructional rigor and student interest in the following topics: cut flowers, container-growing media, fertilizers, hydroponics,…

  2. Biology relevant to space radiation

    SciTech Connect

    Fry, R.J.M.

    1996-08-01

    The biological effects of the radiations to which mankind on earth are exposed are becoming known with an increasing degree of detail. This knowledge is the basis of the estimates of risk that, in turn, fosters a comprehensive and evolving radiation protection system. The substantial body of information has been, and is being, applied to questions about the biological effects of radiation is space and the associated risk estimates. The purpose of this paper is not to recount all the biological effect of radiation but to concentrate on those that may occur as a result from exposure to the radiations encountered in space. In general, the biological effects of radiation in space are the same as those on earth. However, the evidence that the effects on certain tissues by the heaviest-charged particles can be interpreted on the basis of our knowledge about other high-LET radiation is equivocal. This specific question will be discussed in greater detail later. It is important to point out the that there are only limited data about the effects on humans of two components of the radiations in space, namely protons and heavy ions. Thus predictions of effects on space crews are based on experimental systems exposed on earth at rates and fluences that are higher than those in space and one the effects of gamma or x rays with estimates of the equivalent doses using quality factors.

  3. Biology relevant to space radiation

    SciTech Connect

    Fry, R.J.M.

    1997-04-30

    There are only very limited data on the health effects to humans from the two major components of the radiations in space, namely protons and heavy ions. As a result, predictions of the accompanying effects must be based either on (1) data generated through studies of experimental systems exposed on earth at rates and fluences higher than those in space, or (2) extrapolations from studies of gamma and x rays. Better information is needed about the doses, dose rates, and the energy and LET spectra of the radiations at the organ level that are anticipated to be encountered during extended space missions. In particular, there is a need for better estimates of the relationship between radiation quality and biological effects. In the case of deterministic effects, it is the threshold that is important. The possibility of the occurrence of a large solar particle event (SPE) requires that such effects be considered during extended space missions. Analyses suggest, however, that it is feasible to provide sufficient shielding so as to reduce such effects to acceptable levels, particularly if the dose rates can be limited. If these analyses prove correct, the primary biological risks will be the stochastic effects (latent cancer induction). The contribution of one large SPE to the risk of stochastic effects while undesirable will not be large in comparison to the potential total dose on a mission of long duration.

  4. Mammalian lipoxygenases and their biological relevance

    PubMed Central

    Kuhn, Hartmut; Banthiya, Swathi; van Leyen, Klaus

    2015-01-01

    Lipoxygenases (LOXs) form a heterogeneous class of lipid peroxidizing enzymes, which have been implicated in cell proliferation and differentiation but also in the pathogenesis of various diseases with major public health relevance. As other fatty acid dioxygenases LOX oxidize polyunsaturated fatty acids to their corresponding hydroperoxy derivatives, which are further transformed to bioactive lipid mediators (eicosanoids and related substances). On the other hand, lipoxygenases are key players in regulation of the cellular redox homeostasis, which is an important element in gene expression regulation. Although the first mammalian lipoxygenases were discovered 40 years ago and although the enzymes have been well characterized with respect to their structural and functional properties the biological roles of the different lipoxygenase isoforms are not completely understood. This review is aimed at summarizing the current knowledge on the physiological roles of different mammalian LOX-isoforms and their patho-physiological function in inflammatory, metabolic, hyperproliferative, neurodegenerative and infectious disorders. PMID:25316652

  5. Biologically Relevant Glycopeptides: Synthesis and Applications

    NASA Astrophysics Data System (ADS)

    Bennett, Clay S.; Payne, Richard J.; Koeller, Kathryn M.; Wong, Chi-Huey

    Over the past two decades interest in glycopeptides and glycoproteins has intensified, due in part to the development of new and efficient methods for the synthesis of these compounds. This includes a number of chemical and enzymatic techniques for incorporating glycosylation onto the peptide backbone as well as the introduction of powerful peptide ligation methods for the construction of glycoproteins. This review discusses these methods with a special emphasis on biologically relevant glycopeptides and glycoproteins. This includes the development of a number of antigens which hold promise as potential vaccines for HIV, cancer, or a host of other clinically important diseases. In addition the development of new antibiotics aimed at overcoming the problem of resistance will be discussed. Finally, chemical and enzymatic methods for the construction of glycopeptide mimetics will be described.

  6. Capillary electrochromatography of biologically relevant flavonoids.

    PubMed

    Stöggl, Wolfgang M; Huck, Christian W; Stecher, Günther; Bonn, Günther K

    2006-02-01

    Flavonoids were separated utilizing CEC technique. Baseline separation of biologically relevant flavonoids was obtained using a 100 microm ID fused-silica capillary filled with 3 microm Silica-C18 material and an optimized mobile phase comprising of 20 mM Tris-HCl (pH 6.5), ACN and water at a ratio of 10/40/50 v/v/v. Separations were carried out at 25 kV and a column temperature of 25 degrees C. The influence of relevant parameters for the CEC separation, such as buffer concentration, pH, separation voltage, and ACN concentration, was investigated and optimized. Dependencies of the electroendoosmotic flow (EOF) on these parameters and effects on the resolution of the analytes were studied. During analyses the solvents used for dissolving the samples turned out to have significant effects on the separation of flavonoids. The optimized system was then successfully used for the separation of the flavonoids epicatechin, myricetin, quercetin, naringenin, and hesperetin. CEC turned out to be a useful complementary tool for the economic analysis of flavonoids in addition to common HPLC, muHPLC, and CE methodologies. This method can be used for real applications in phytomics. PMID:16411273

  7. Teaching Secondary School Biology for Social Relevance.

    ERIC Educational Resources Information Center

    Meyer, G. Rex; And Others

    Since the 1960's biology teaching in secondary schools has been transformed from a formal approach reflecting the structure of the discipline and mirroring the concerns of the scientific community to a broad-based approach reflecting the concerns of society as a whole. The aim of biology education today is to heighten awareness, improve students'…

  8. Future development of biologically relevant dosimetry.

    PubMed

    Palmans, H; Rabus, H; Belchior, A L; Bug, M U; Galer, S; Giesen, U; Gonon, G; Gruel, G; Hilgers, G; Moro, D; Nettelbeck, H; Pinto, M; Pola, A; Pszona, S; Schettino, G; Sharpe, P H G; Teles, P; Villagrasa, C; Wilkens, J J

    2015-01-01

    Proton and ion beams are radiotherapy modalities of increasing importance and interest. Because of the different biological dose response of these radiations as compared with high-energy photon beams, the current approach of treatment prescription is based on the product of the absorbed dose to water and a biological weighting factor, but this is found to be insufficient for providing a generic method to quantify the biological outcome of radiation. It is therefore suggested to define new dosimetric quantities that allow a transparent separation of the physical processes from the biological ones. Given the complexity of the initiation and occurrence of biological processes on various time and length scales, and given that neither microdosimetry nor nanodosimetry on their own can fully describe the biological effects as a function of the distribution of energy deposition or ionization, a multiscale approach is needed to lay the foundation for the aforementioned new physical quantities relating track structure to relative biological effectiveness in proton and ion beam therapy. This article reviews the state-of-the-art microdosimetry, nanodosimetry, track structure simulations, quantification of reactive species, reference radiobiological data, cross-section data and multiscale models of biological response in the context of realizing the new quantities. It also introduces the European metrology project, Biologically Weighted Quantities in Radiotherapy, which aims to investigate the feasibility of establishing a multiscale model as the basis of the new quantities. A tentative generic expression of how the weighting of physical quantities at different length scales could be carried out is presented. PMID:25257709

  9. The Biological Relevance of Artificial Life: Lessons from Artificial Intelligence

    NASA Technical Reports Server (NTRS)

    Colombano, Silvano

    2000-01-01

    There is no fundamental reason why A-life couldn't simply be a branch of computer science that deals with algorithms that are inspired by, or emulate biological phenomena. However, if these are the limits we place on this field, we miss the opportunity to help advance Theoretical Biology and to contribute to a deeper understanding of the nature of life. The history of Artificial Intelligence provides a good example, in that early interest in the nature of cognition quickly was lost to the process of building tools, such as "expert systems" that, were certainly useful, but provided little insight in the nature of cognition. Based on this lesson, I will discuss criteria for increasing the biological relevance of A-life and the probability that this field may provide a theoretical foundation for Biology.

  10. Behavior of nanoceria in biologically-relevant environments

    SciTech Connect

    Kumar, Amit; Das, Soumen; Munusamy, Prabhakaran; Self, William; Baer, Donald R.; Sayle, Dean C.; Seal, Sudipta

    2014-09-08

    Cerium oxide nanoparticles (CNPs) have gained a considerable attention in biological research due to their anti-oxidant like behaviour and regenerative nature. The current literature on CNPs reports many successful attempts on harnessing the beneficial therapeutic properties in biology. However studies have also shown toxicity effect with some types of CNPs. This review discusses issues associated with the behaviours of CNPs in biological systems and identifies key knowledge gaps. We explore how salient physicochemical properties (size, surface chemistry, surface stabilizers) contribute to the potential positive and negative aspects of nanoceria in biological systems. Based on variations of results reported in the literature, important issues need to be addressed. Are we really studying the same particles with slight variations in size and physicochemical properties or do the particles being examined have fundamentally different behaviours? Are the variations observed in the result of differences in the initial properties of the particles or the results of downstream effects that emerge as the particles are prepared for specific studies and they interact with biological or other environmental moieties? How should particles be appropriately prepared for relevant environmental/toxicology/safety studies? It is useful to recognize that nanoparticles encompass some of the same complexities and variability associated with biological components

  11. Hands-on-Entropy, Energy Balance with Biological Relevance

    NASA Astrophysics Data System (ADS)

    Reeves, Mark

    2015-03-01

    Entropy changes underlie the physics that dominates biological interactions. Indeed, introductory biology courses often begin with an exploration of the qualities of water that are important to living systems. However, one idea that is not explicitly addressed in most introductory physics or biology textbooks is important contribution of the entropy in driving fundamental biological processes towards equilibrium. From diffusion to cell-membrane formation, to electrostatic binding in protein folding, to the functioning of nerve cells, entropic effects often act to counterbalance deterministic forces such as electrostatic attraction and in so doing, allow for effective molecular signaling. A small group of biology, biophysics and computer science faculty have worked together for the past five years to develop curricular modules (based on SCALEUP pedagogy). This has enabled students to create models of stochastic and deterministic processes. Our students are first-year engineering and science students in the calculus-based physics course and they are not expected to know biology beyond the high-school level. In our class, they learn to reduce complex biological processes and structures in order model them mathematically to account for both deterministic and probabilistic processes. The students test these models in simulations and in laboratory experiments that are biologically relevant such as diffusion, ionic transport, and ligand-receptor binding. Moreover, the students confront random forces and traditional forces in problems, simulations, and in laboratory exploration throughout the year-long course as they move from traditional kinematics through thermodynamics to electrostatic interactions. This talk will present a number of these exercises, with particular focus on the hands-on experiments done by the students, and will give examples of the tangible material that our students work with throughout the two-semester sequence of their course on introductory

  12. The allosteric modulation of lipases and its possible biological relevance

    PubMed Central

    Köhler, Jens; Wünsch, Bernhard

    2007-01-01

    Background During the development of an enantioselective synthesis using the lipase from Mucor miehei an unusual reaction course was observed, which was analyzed precisely. For the first time an allosteric modulation of a lipase changing its selectivity was shown. Theory Considering the biological relevance of the discovered regulation mechanism we developed a theory that describes the regulation of energy homeostasis and fat metabolism. Conclusion This theory represents a new approach to explain the cause of the metabolic syndrome and provides an innovative basis for further research activity. PMID:17825093

  13. Behavioural biology: an effective and relevant conservation tool.

    PubMed

    Buchholz, Richard

    2007-08-01

    'Conservation behaviour' is a young discipline that investigates how proximate and ultimate aspects of the behaviour of an animal can be of value in preventing the loss of biodiversity. Rumours of its demise are unfounded. Conservation behaviour is quickly building a capacity to positively influence environmental decision making. The theoretical framework used by animal behaviourists is uniquely valuable to elucidating integrative solutions to human-wildlife conflicts, efforts to reintroduce endangered species and reducing the deleterious effects of ecotourism. Conservation behaviourists must join with other scientists under the multidisciplinary umbrella of conservation biology without giving up on their focus: the mechanisms, development, function and evolutionary history of individual differences in behaviour. Conservation behaviour is an increasingly relevant tool in the preservation of nature. PMID:17590477

  14. Density Functional Theory of Biologically Relevant Metal Centers

    NASA Astrophysics Data System (ADS)

    Siegbahn, Per E. M.; Blomberg, Margareta R. A.

    1999-10-01

    Recent applications of density functional theory to biologically relevant metal centers are reviewed. The emphasis is on reaction mechanisms, structures, and modeling. The accuracy of different functionals is discussed for standard benchmark tests of first- and second-row molecules and for transition metal systems. Modeling aspects of the protein metal complexes are discussed regarding both the size of the model being treated quantum mechanically and the treatment of the protein surrounding it. To illustrate the effects, structures computed without the effects of the protein are compared with experimental structures from enzymes, and results from simple dielectric models of the protein for electron transfer processes are described. The choice of spin state is discussed for multimetal complexes. Examples of mechanisms studied recently by density functional theory are described, such as O2 and methane activation in methane monooxygenase and O2 formation in photosystem II.

  15. Biclustering Methods: Biological Relevance and Application in Gene Expression Analysis

    PubMed Central

    Oghabian, Ali; Kilpinen, Sami; Hautaniemi, Sampsa; Czeizler, Elena

    2014-01-01

    DNA microarray technologies are used extensively to profile the expression levels of thousands of genes under various conditions, yielding extremely large data-matrices. Thus, analyzing this information and extracting biologically relevant knowledge becomes a considerable challenge. A classical approach for tackling this challenge is to use clustering (also known as one-way clustering) methods where genes (or respectively samples) are grouped together based on the similarity of their expression profiles across the set of all samples (or respectively genes). An alternative approach is to develop biclustering methods to identify local patterns in the data. These methods extract subgroups of genes that are co-expressed across only a subset of samples and may feature important biological or medical implications. In this study we evaluate 13 biclustering and 2 clustering (k-means and hierarchical) methods. We use several approaches to compare their performance on two real gene expression data sets. For this purpose we apply four evaluation measures in our analysis: (1) we examine how well the considered (bi)clustering methods differentiate various sample types; (2) we evaluate how well the groups of genes discovered by the (bi)clustering methods are annotated with similar Gene Ontology categories; (3) we evaluate the capability of the methods to differentiate genes that are known to be specific to the particular sample types we study and (4) we compare the running time of the algorithms. In the end, we conclude that as long as the samples are well defined and annotated, the contamination of the samples is limited, and the samples are well replicated, biclustering methods such as Plaid and SAMBA are useful for discovering relevant subsets of genes and samples. PMID:24651574

  16. Biclustering methods: biological relevance and application in gene expression analysis.

    PubMed

    Oghabian, Ali; Kilpinen, Sami; Hautaniemi, Sampsa; Czeizler, Elena

    2014-01-01

    DNA microarray technologies are used extensively to profile the expression levels of thousands of genes under various conditions, yielding extremely large data-matrices. Thus, analyzing this information and extracting biologically relevant knowledge becomes a considerable challenge. A classical approach for tackling this challenge is to use clustering (also known as one-way clustering) methods where genes (or respectively samples) are grouped together based on the similarity of their expression profiles across the set of all samples (or respectively genes). An alternative approach is to develop biclustering methods to identify local patterns in the data. These methods extract subgroups of genes that are co-expressed across only a subset of samples and may feature important biological or medical implications. In this study we evaluate 13 biclustering and 2 clustering (k-means and hierarchical) methods. We use several approaches to compare their performance on two real gene expression data sets. For this purpose we apply four evaluation measures in our analysis: (1) we examine how well the considered (bi)clustering methods differentiate various sample types; (2) we evaluate how well the groups of genes discovered by the (bi)clustering methods are annotated with similar Gene Ontology categories; (3) we evaluate the capability of the methods to differentiate genes that are known to be specific to the particular sample types we study and (4) we compare the running time of the algorithms. In the end, we conclude that as long as the samples are well defined and annotated, the contamination of the samples is limited, and the samples are well replicated, biclustering methods such as Plaid and SAMBA are useful for discovering relevant subsets of genes and samples. PMID:24651574

  17. Identifying Biologically Relevant Cues in the Hydrologic Regime

    NASA Astrophysics Data System (ADS)

    Lovellford, R. M.; Flitcroft, R.; Santelmann, M. V.; Grant, G. E.; Safeeq, M.; Lewis, S.

    2012-12-01

    Seasonal variation in hydrologic discharge and temperature defines the availability, connectivity, and quality of lentic habitats. Native aquatic species are adapted to local hydrologic regimes , eg. magnitudes and rates of change . In recent decades, biologically relevant hydrologic conditions have been identified that are necessary to maintain habitat conditions for aquatic obligate species. Another element of hydrologic regimes important to aquatic species are the cues that inform individuals of seasonal changes that precipitate important physiological or behavioral alterations. There is a need for hydrologists, biologists, and ecologists, to define biologically significant cues within the hydrologic regime. Coho salmon (Onchorhynchus kisutch), an anadromous species of Pacific salmon, offers an example of sensitivity to environmental cues. Examinations of the run-timing of mature adult coho salmon on the North Umpqua River, OR, indicate that migration timing coincides with decreasing fall water temperatures prior to increasing winter discharge. For this species, adults leave the ocean ready to spawn. Adults need to spawn in small headwater streams prior to the onset of intense storm conditions that prohibit effective deposition or fertilization of eggs in redds (salmon nests).Therefore, the timing of spawning must be carefully executed. Understanding the cues that trigger specific behaviors gives insight to the processes that provide ecosystem stability and flexibility over time. Improved understanding of these cues may help us protect freshwater ecosystems and improve management for endangered species.

  18. Biological and clinical relevance of stem cells in pancreatic adenocarcinoma

    PubMed Central

    Rasheed, Zeshaan A; Matsui, William

    2013-01-01

    Cancer stem cells (CSC) have been identified in a growing number of human malignancies. CSC are functionally defined by their ability to self-renew and recapitulate tumors in the ectopic setting, and a growing number of studies have shown that they display other functional characteristics, such as invasion and drug resistance. These unique functional properties implicate a role for CSC in clinical consequences, such as initial tumor formation, relapse following treatment, metastasis, and resistance, suggesting they are a major factor in directing clinical outcomes. Pancreatic adenocarcinoma is a highly-aggressive disease with a propensity for early metastasis and drug resistance. Tumorigenic pancreatic cancer cells have been identified using the cell surface antigens CD44, CD24, and CD133, as well as the high expression of aldehyde dehydrogenase (ALDH). In vitro and in vivo studies have shown that ALDH- and CD133-expressing pancreatic CSC have a greater propensity for metastasis, and ALDH-expressing CSC have been shown to be resistant to conventional chemotherapy. In clinical samples from patients with resected pancreatic adenocarcinoma, the presence of ALDH-expressing CSC was associated with worse overall survival. The development of CSC-targeting therapies might be important in changing the clinical outcomes of patients with this disease, and others and we have begun to identify novel compounds that block CSC function. This review will discuss the biological and clinical relevance of CSC in pancreatic cancer, and will discuss novel therapeutic strategies to target them. PMID:22320910

  19. Characterization of Nanoparticle Aggregation in Biologically Relevant Fluids

    NASA Astrophysics Data System (ADS)

    McEnnis, Kathleen; Lahann, Joerg

    Nanoparticles (NPs) are often studied as drug delivery vehicles, but little is known about their behavior in blood once injected into animal models. If the NPs aggregate in blood, they will be shunted to the liver or spleen instead of reaching the intended target. The use of animals for these experiments is costly and raises ethical questions. Typically dynamic light scattering (DLS) is used to analyze aggregation behavior, but DLS cannot be used because the components of blood also scatter light. As an alternative, a method of analyzing NPs in biologically relevant fluids such as blood plasma has been developed using nanoparticle tracking analysis (NTA) with fluorescent filters. In this work, NTA was used to analyze the aggregation behavior of fluorescent polystyrene NPs with different surface modifications in blood plasma. It was expected that different surface chemistries on the particles will change the aggregation behavior. The effect of the surface modifications was investigated by quantifying the percentage of NPs in aggregates after addition to blood plasma. The use of this characterization method will allow for better understanding of particle behavior in the body, and potential problems, specifically aggregation, can be addressed before investing in in vivo studies.

  20. Reviewing the relevance of fluorescence in biological systems.

    PubMed

    Lagorio, M Gabriela; Cordon, Gabriela B; Iriel, Analia

    2015-09-26

    Fluorescence is emitted by diverse living organisms. The analysis and interpretation of these signals may give information about their physiological state, ways of communication among species and the presence of specific chemicals. In this manuscript we review the state of the art in the research on the fluorescence emitted by plant leaves, fruits, flowers, avians, butterflies, beetles, dragonflies, millipedes, cockroaches, bees, spiders, scorpions and sea organisms and discuss its relevance in nature. PMID:26103563

  1. Streptococcus pyogenes biofilms—formation, biology, and clinical relevance

    PubMed Central

    Fiedler, Tomas; Köller, Thomas; Kreikemeyer, Bernd

    2015-01-01

    Streptococcus pyogenes (group A streptococci, GAS) is an exclusive human bacterial pathogen. The virulence potential of this species is tremendous. Interactions with humans range from asymptomatic carriage over mild and superficial infections of skin and mucosal membranes up to systemic purulent toxic-invasive disease manifestations. Particularly the latter are a severe threat for predisposed patients and lead to significant death tolls worldwide. This places GAS among the most important Gram-positive bacterial pathogens. Many recent reviews have highlighted the GAS repertoire of virulence factors, regulators and regulatory circuits/networks that enable GAS to colonize the host and to deal with all levels of the host immune defense. This covers in vitro and in vivo studies, including animal infection studies based on mice and more relevant, macaque monkeys. It is now appreciated that GAS, like many other bacterial species, do not necessarily exclusively live in a planktonic lifestyle. GAS is capable of microcolony and biofilm formation on host cells and tissues. We are now beginning to understand that this feature significantly contributes to GAS pathogenesis. In this review we will discuss the current knowledge on GAS biofilm formation, the biofilm-phenotype associated virulence factors, regulatory aspects of biofilm formation, the clinical relevance, and finally contemporary treatment regimens and future treatment options. PMID:25717441

  2. Student perception of relevance of biology content to everyday life: A study in higher education biology courses

    NASA Astrophysics Data System (ADS)

    Himschoot, Agnes Rose

    The purpose of this mixed method case study was to examine the effects of methods of instruction on students' perception of relevance in higher education non-biology majors' courses. Nearly ninety percent of all students in a liberal arts college are required to take a general biology course. It is proposed that for many of those students, this is the last science course they will take for life. General biology courses are suspected of discouraging student interest in biology with large enrollment, didactic instruction, covering a huge amount of content in one semester, and are charged with promoting student disengagement with biology by the end of the course. Previous research has been aimed at increasing student motivation and interest in biology as measured by surveys and test results. Various methods of instruction have been tested and show evidence of improved learning gains. This study focused on students' perception of relevance of biology content to everyday life and the methods of instruction that increase it. A quantitative survey was administered to assess perception of relevance pre and post instruction over three topics typically taught in a general biology course. A second quantitative survey of student experiences during instruction was administered to identify methods of instruction used in the course lecture and lab. While perception of relevance dropped in the study, qualitative focus groups provided insight into the surprising results by identifying topics that are more relevant than the ones chosen for the study, conveying the affects of the instructor's personal and instructional skills on student engagement, explanation of how active engagement during instruction promotes understanding of relevance, the roll of laboratory in promoting students' understanding of relevance as well as identifying external factors that affect student engagement. The study also investigated the extent to which gender affected changes in students' perception of

  3. Biologically relevant neural network architectures for support vector machines.

    PubMed

    Jändel, Magnus

    2014-01-01

    Neural network architectures that implement support vector machines (SVM) are investigated for the purpose of modeling perceptual one-shot learning in biological organisms. A family of SVM algorithms including variants of maximum margin, 1-norm, 2-norm and ν-SVM is considered. SVM training rules adapted for neural computation are derived. It is found that competitive queuing memory (CQM) is ideal for storing and retrieving support vectors. Several different CQM-based neural architectures are examined for each SVM algorithm. Although most of the sixty-four scanned architectures are unconvincing for biological modeling four feasible candidates are found. The seemingly complex learning rule of a full ν-SVM implementation finds a particularly simple and natural implementation in bisymmetric architectures. Since CQM-like neural structures are thought to encode skilled action sequences and bisymmetry is ubiquitous in motor systems it is speculated that trainable pattern recognition in low-level perception has evolved as an internalized motor programme. PMID:24126252

  4. Relevance of ammonium oxidation within biological soil crust communities

    USGS Publications Warehouse

    Johnson, S.L.; Budinoff, C.R.; Belnap, J.; Garcia-Pichel, F.

    2005-01-01

    Thin, vertically structured topsoil communities that become ecologically important in arid regions (biological soil crusts or BSCs) are responsible for much of the nitrogen inputs into pristine arid lands. We studied N2 fixation and ammonium oxidation (AO) at subcentimetre resolution within BSCs from the Colorado Plateau. Pools of dissolved porewater nitrate/ nitrite, ammonium and organic nitrogen in wetted BSCs were high in comparison with those typical of aridosoils. They remained stable during incubations, indicating that input and output processes were of similar magnitude. Areal N2 fixation rates (6.5-48 ??mol C2H2 m-2 h -1) were high, the vertical distribution of N2 fixation peaking close to the surface if populations of heterocystous cyanobacteria were present, but in the subsurface if they were absent. Areal AO rates (19-46 ??mol N m-2 h-1) were commensurate with N2 fixation inputs. When considering oxygen availability, AO activity invariably peaked 2-3 mm deep and was limited by oxygen (not ammonium) supply. Most probable number (MPN)-enumerated ammonia-oxidizing bacteria (6.7-7.9 ?? 103 cells g-1 on average) clearly peaked at 2-3 mm depth. Thus, AO (hence nitrification) is a spatially restricted but important process in the nitrogen cycling of BSC, turning much of the biologically fixed nitrogen into oxidized forms, the fate of which remains to be determined.

  5. What Is the Biological and Clinical Relevance of Fibrin?

    PubMed

    Litvinov, Rustem I; Weisel, John W

    2016-06-01

    As our knowledge of the structure and functions of fibrinogen and fibrin has increased tremendously, several key findings have given some people a superficial impression that the biological and clinical significance of these clotting proteins may be less than earlier thought. Most strikingly, studies of fibrinogen knockout mice demonstrated that many of these mice survive to weaning and beyond, suggesting that fibrin(ogen) may not be entirely necessary. Humans with afibrinogenemia also survive. Furthermore, in recent years, the major emphasis in the treatment of arterial thrombosis has been on inhibition of platelets, rather than fibrin. In contrast to the initially apparent conclusions from these results, it has become increasingly clear that fibrin is essential for hemostasis; is a key factor in thrombosis; and plays an important biological role in infection, inflammation, immunology, and wound healing. In addition, fibrinogen replacement therapy has become a preferred, major treatment for severe bleeding in trauma and surgery. Finally, fibrin is a unique biomaterial and is used as a sealant or glue, a matrix for cells, a scaffold for tissue engineering, and a carrier and/or a vector for targeted drug delivery. PMID:27056152

  6. Student Perception of Relevance of Biology Content to Everyday Life: A Study in Higher Education Biology Courses

    ERIC Educational Resources Information Center

    Himschoot, Agnes Rose

    2012-01-01

    The purpose of this mixed method case study was to examine the effects of methods of instruction on students' perception of relevance in higher education non-biology majors' courses. Nearly ninety percent of all students in a liberal arts college are required to take a general biology course. It is proposed that for many of those students, this is…

  7. Terahertz vibrational properties of water nanoclusters relevant to biology.

    PubMed

    Johnson, Keith

    2012-01-01

    Water nanoclusters are shown from first-principles calculations to possess unique terahertz-frequency vibrational modes in the 1-6 THz range, corresponding to O-O-O "bending," "squashing," and "twisting" "surface" distortions of the clusters. The cluster molecular-orbital LUMOs are huge Rydberg-like "S," "P," "D," and "F" orbitals that accept an extra electron via optical excitation, ionization, or electron donation from interacting biomolecules. Dynamic Jahn-Teller coupling of these "hydrated-electron" orbitals to the THz vibrations promotes such water clusters as vibronically active "structured water" essential to biomolecular function such as protein folding. In biological microtubules, confined water-cluster THz vibrations may induce their "quantum coherence" communicated by Jahn-Teller phonons via coupling of the THz electromagnetic field to the water clusters' large electric dipole moments. PMID:23277672

  8. Extracellular Vesicles: Composition, Biological Relevance, and Methods of Study

    PubMed Central

    Zaborowski, MikoŁaj P.; Balaj, Leonora; Breakefield, Xandra O.; Lai, Charles P.

    2015-01-01

    The release of extracellular vesicles (EVs), including exosomes and microvesicles, is a phenomenon shared by many cell types as a means of communicating with other cells and also potentially removing cell contents. The cargo of EVs includes the proteins, lipids, nucleic acids, and membrane receptors of the cells from which they originate. EVs released into the extracellular space can enter body fluids and potentially reach distant tissues. Once taken up by neighboring and/or distal cells, EVs can transfer functional cargo that may alter the status of recipient cells, thereby contributing to both physiological and pathological processes. In this article, we will focus on EV composition, mechanisms of uptake, and their biological effects on recipient cells. We will also discuss established and recently developed methods used to study EVs, including isolation, quantification, labeling and imaging protocols, as well as RNA analysis. PMID:26955082

  9. Chiral alkynylcarbinols from marine sponges: asymmetric synthesis and biological relevance.

    PubMed

    Listunov, Dymytrii; Maraval, Valérie; Chauvin, Remi; Génisson, Yves

    2015-01-01

    Covering: up to March 2014. Previous review on the topic: B. W. Gung, C. R. Chim., 2009, 12, 489-505. Chiral α-functional lipidic propargylic alcohols extracted from marine sponges, in particular of the pacific genus Petrosia, constitute a class of acetylenic natural products exhibiting remarkable in vitro biological activities, especially anti-tumoral cytotoxicity. These properties, associated to functionalities that are uncommon among natural products, have prompted recent projects on asymmetric total synthesis. On the basis of a three-sector structural typology, three main sub-types of secondary alkynylcarbinols (with either alkyl, alkenyl, or alkynyl as the second substituent) can be identified as the minimal pharmacophoric units. Selected natural products containing these functionalities have been targeted using previously known or on purpose-designed procedures, where the stereo-determining step can be: (i) a C-C bond forming reaction (e.g. the Zn-mediated addition of alkynyl nucleophiles to aldehydes in the presence of chiral aminoalcohols), (ii) a functional layout (e.g. the asymmetric organo- or metallo-catalytic reduction of ynones), or (iii) an enantiomeric resolution (e.g. a lipase-mediated kinetic resolution via acetylation). The promising medicinal importance of these targets is finally surveyed, and future investigation prospects are proposed, such as: (i) further total synthesis of known or future extraction products; (ii) the synthesis of non-natural analogues, with simpler lipophilic environments of the alkynylcarbinol-based pharmacophoric units; (iii) the variation and optimization of both the pharmacophoric units and their lipophilic environment; and (iv) investigations into the biological mode of action of these unique structures. PMID:25275665

  10. Encoding and processing biologically relevant temporal information in electrosensory systems.

    PubMed

    Fortune, E S; Rose, G J; Kawasaki, M

    2006-06-01

    Wave-type weakly electric fish are specialists in time-domain processing: behaviors in these animals are often tightly correlated with the temporal structure of electrosensory signals. Behavioral responses in these fish can be dependent on differences in the temporal structure of electrosensory signals alone. This feature has facilitated the study of temporal codes and processing in central nervous system circuits of these animals. The temporal encoding and mechanisms used to transform temporal codes in the brain have been identified and characterized in several species, including South American gymnotid species and in the African mormyrid genus Gymnarchus. These distantly related groups use similar strategies for neural computations of information on the order of microseconds, milliseconds, and seconds. Here, we describe a suite of mechanisms for behaviorally relevant computations of temporal information that have been elucidated in these systems. These results show the critical role that behavioral experiments continue to have in the study of the neural control of behavior and its evolution. PMID:16450118

  11. IDENTIFICATION OF BIOLOGICALLY RELEVANT GENES USING A DATABASE OF RAT LIVER AND KIDNEY BASELINE GENE EXPRESSION

    EPA Science Inventory

    Microarray data from independent labs and studies can be compared to potentially identify toxicologically and biologically relevant genes. The Baseline Animal Database working group of HESI was formed to assess baseline gene expression from microarray data derived from control or...

  12. FireDB: a compendium of biological and pharmacologically relevant ligands.

    PubMed

    Maietta, Paolo; Lopez, Gonzalo; Carro, Angel; Pingilley, Benjamin J; Leon, Leticia G; Valencia, Alfonso; Tress, Michael L

    2014-01-01

    FireDB (http://firedb.bioinfo.cnio.es) is a curated inventory of catalytic and biologically relevant small ligand-binding residues culled from the protein structures in the Protein Data Bank. Here we present the important new additions since the publication of FireDB in 2007. The database now contains an extensive list of manually curated biologically relevant compounds. Biologically relevant compounds are informative because of their role in protein function, but they are only a small fraction of the entire ligand set. For the remaining ligands, the FireDB provides cross-references to the annotations from publicly available biological, chemical and pharmacological compound databases. FireDB now has external references for 95% of contacting small ligands, making FireDB a more complete database and providing the scientific community with easy access to the pharmacological annotations of PDB ligands. In addition to the manual curation of ligands, FireDB also provides insights into the biological relevance of individual binding sites. Here, biological relevance is calculated from the multiple sequence alignments of related binding sites that are generated from all-against-all comparison of each FireDB binding site. The database can be accessed by RESTful web services and is available for download via MySQL. PMID:24243844

  13. Making Biology Learning Relevant to Students: Integrating People, History, and Context into College Biology Teaching

    ERIC Educational Resources Information Center

    Chamany, Katayoun; Allen, Deborah; Tanner, Kimberly

    2008-01-01

    Teaching students to make connections between what they learn in the classroom and what they see in everyday life is imperative. As biology instructors, they may choose to teach biology devoid of social context, believing that students can make these connections on their own. However, students model their instructors' behaviors, and follow their…

  14. Beyond arousal and valence: The importance of the biological versus social relevance of emotional stimuli

    PubMed Central

    Sakaki, Michiko; Niki, Kazuhisa; Mather, Mara

    2012-01-01

    The present study addressed the hypothesis that emotional stimuli relevant to survival or reproduction (biologically emotional stimuli) automatically affect cognitive processing (e.g., attention; memory), while those relevant to social life (socially emotional stimuli) require elaborative processing to modulate attention and memory. Results of our behavioral studies showed that: a) biologically emotional images hold attention more strongly than socially emotional images, b) memory for biologically emotional images was enhanced even with limited cognitive resources, but c) memory for socially emotional images was enhanced only when people had sufficient cognitive resources at encoding. Neither images’ subjective arousal nor their valence modulated these patterns. A subsequent functional magnetic resonance imaging study revealed that biologically emotional images induced stronger activity in visual cortex and greater functional connectivity between amygdala and visual cortex than did socially emotional images. These results suggest that the interconnection between the amygdala and visual cortex supports enhanced attention allocation to biological stimuli. In contrast, socially emotional images evoked greater activity in medial prefrontal cortex (MPFC) and yielded stronger functional connectivity between amygdala and MPFC than biological images. Thus, it appears that emotional processing of social stimuli involves elaborative processing requiring frontal lobe activity. PMID:21964552

  15. Biological relevance of decamethylcyclopentasiloxane (D5) induced rat uterine endometrial adenocarcinoma tumorigenesis: Mode of action and relevance to humans.

    PubMed

    Klaunig, James E; Dekant, Wolfgang; Plotzke, Kathy; Scialli, Anthony R

    2016-02-01

    Decamethylcyclopentasiloxane (D5) is a cyclic siloxane used in the production and formulation of consumer products with potential exposure to manufacturing workers, consumer, and the general public. Following a combined 2-year inhalation chronic bioassay performed in Fischer 344 (F344) rats, an increase in uterine endometrial adenocarcinomas was noted at the highest concentration to which animals were exposed. No other neoplasms were detected. In this study, a dose of 160 ppm produced an incidence of 8% endometrial adenocarcinomas. Based on a number of experimental studies with D5, the current manuscript examines the biological relevance and possible modes of action for the uterine endometrial adenocarcinomas observed in the rat following chronic exposure to D5. Variable rates of spontaneous uterine endometrial adenocarcinomas have been reported for untreated F344 CrlBr rats. As such, we concluded that the slight increase in uterine endometrial adenocarcinomas observed in the D5 chronic bioassay might not be the result of D5 exposure but may be related to variability of the spontaneous tumor incidence in this strain of rat. However, if the uterine endometrial adenocarcinomas are related to D5-exposure, alteration in the estrous cycle in the aging F344 rat is the most likely mode of action. D5 is not genotoxic or estrogenic. The alteration in the estrous cycle is caused by a decrease in progesterone with an increase in the estrogen:progesterone ratio most likely induced by a decrease in prolactin concentration. Available data support that exposure to D5 influences prolactin concentration. Although the effects on prolactin concentrations in a number of experiments were not always consistent, the available data support the conclusion that D5 is acting via a dopamine receptor agonist-like mechanism to alter the pituitary control of the estrous cycle. In further support of this mode of action, studies in F344 aged animals showed that the effects of D5 on estrous

  16. Making developmental biology relevant to undergraduates in an era of economic rationalism in Australia.

    PubMed

    Key, Brian; Nurcombe, Victor

    2003-01-01

    This report describes the road map we followed at our university to accommodate three main factors: financial pressure within the university system; desire to enhance the learning experience of undergraduates; and motivation to increase the prominence of the discipline of developmental biology in our university. We engineered a novel, multi-year undergraduate developmental biology program which was "student-oriented," ensuring that students were continually exposed to the underlying principles and philosophy of this discipline throughout their undergraduate career. Among its key features are introductory lectures in core courses in the first year, which emphasize the relevance of developmental biology to tissue engineering, reproductive medicine, therapeutic approaches in medicine, agriculture and aquaculture. State-of-the-art animated computer graphics and images of high visual impact are also used. In addition, students are streamed into the developmental biology track in the second year, using courses like human embryology and courses shared with cell biology, which include practicals based on modern experimental approaches. Finally, fully dedicated third-year courses in developmental biology are undertaken in conjunction with stand-alone practical courses where students experiencefirst-hand work in a research laboratory. Our philosophy is a "cradle-to-grave" approach to the education of undergraduates so as to prepare highly motivated, enthusiastic and well-educated developmental biologists for entry into graduate programs and ultimately post-doctoral research. PMID:12705657

  17. Galectin-3 is a marker of favorable prognosis and a biologically relevant molecule in neuroblastic tumors

    PubMed Central

    Veschi, V; Petroni, M; Bartolazzi, A; Altavista, P; Dominici, C; Capalbo, C; Boldrini, R; Castellano, A; McDowell, H P; Pizer, B; Frati, L; Screpanti, I; Gulino, A; Giannini, G

    2014-01-01

    Childhood neuroblastic tumors are characterized by heterogeneous clinical courses, ranging from benign ganglioneuroma (GN) to highly lethal neuroblastoma (NB). Although a refined prognostic evaluation and risk stratification of each tumor patient is becoming increasingly essential to personalize treatment options, currently only few biomolecular markers (essentially MYCN amplification, chromosome 11q status and DNA ploidy) are validated for this purpose in neuroblastic tumors. Here we report that Galectin-3 (Gal-3), a β-galactoside-binding lectin involved in multiple biological functions that has already acquired diagnostic relevance in specific clinical settings, is variably expressed in most differentiated and less aggressive neuroblastic tumors, such as GN and ganglioneuroblastoma, as well as in a subset of NB cases. Gal-3 expression is associated with the INPC histopathological categorization (P<0.001) and Shimada favorable phenotype (P=0.001), but not with other prognostically relevant features. Importantly, Gal-3 expression was associated with a better 5-year overall survival (P=0.003), and with improved cumulative survival in patient subsets at worse prognosis, such as older age at diagnosis, advanced stages or NB histopathological classification. In vitro, Gal-3 expression and nuclear accumulation accompanied retinoic acid-induced cell differentiation in NB cell lines. Forced Gal-3 overexpression increased phenotypic differentiation and substrate adherence, while inhibiting proliferation. Altogether, these findings suggest that Gal-3 is a biologically relevant player for neuroblastic tumors, whose determination by conventional immunohistochemistry might be used for outcome assessment and patient's risk stratification in the clinical setting. PMID:24603328

  18. Population distribution models: species distributions are better modeled using biologically relevant data partitions

    PubMed Central

    2011-01-01

    Background Predicting the geographic distribution of widespread species through modeling is problematic for several reasons including high rates of omission errors. One potential source of error for modeling widespread species is that subspecies and/or races of species are frequently pooled for analyses, which may mask biologically relevant spatial variation within the distribution of a single widespread species. We contrast a presence-only maximum entropy model for the widely distributed oldfield mouse (Peromyscus polionotus) that includes all available presence locations for this species, with two composite maximum entropy models. The composite models either subdivided the total species distribution into four geographic quadrants or by fifteen subspecies to capture spatially relevant variation in P. polionotus distributions. Results Despite high Area Under the ROC Curve (AUC) values for all models, the composite species distribution model of P. polionotus generated from individual subspecies models represented the known distribution of the species much better than did the models produced by partitioning data into geographic quadrants or modeling the whole species as a single unit. Conclusions Because the AUC values failed to describe the differences in the predictability of the three modeling strategies, we suggest using omission curves in addition to AUC values to assess model performance. Dividing the data of a widespread species into biologically relevant partitions greatly increased the performance of our distribution model; therefore, this approach may prove to be quite practical and informative for a wide range of modeling applications. PMID:21929792

  19. Unaffected features of BSA stabilized Ag nanoparticles after storage and reconstitution in biological relevant media.

    PubMed

    Valenti, Laura E; Giacomelli, Carla E

    2015-08-01

    Silver-coated orthopedic implants and silver composite materials have been proposed to produce local biocidal activity at low dose to reduce post-surgery infection that remains one of the major contributions to the patient morbidity. This work presents the synthesis combined with the characterization, colloidal stability in biological relevant media, antimicrobial activity and handling properties of silver nanoparticles (Ag-NP) before and after freeze dry and storage. The nanomaterial was synthesized in aqueous solution with simple, reproducible and low-cost strategies using bovine serum albumin (BSA) as the stabilizing agent. Ag-NP were characterized by means of the size distribution and morphology (UV-vis spectra, dynamic light scattering measurements and TEM images), charge as a function of the pH (zeta potential measurements) and colloidal stability in biological relevant media (UV-vis spectra and dynamic light scattering measurements). Further, the interactions between the protein and Ag-NP were evaluated by surface enhanced Raman spectroscopy (SERS) and the antimicrobial activity was tested with two bacteria strains (namely Staphylococcus aureus and Staphylococcus epidermidis) mainly present in the infections caused by implants and prosthesis in orthopedic surgery. Finally, the Ag-NP dispersed in aqueous solution were dried and stored as long-lasting powders that were easily reconstituted without losing their stability and antimicrobial properties. The proposed methods to stabilize Ag-NP not only produce stable dispersions in media of biological relevance but also long-lasting powders with optimal antimicrobial activity in the nanomolar range. This level is much lower than the cytotoxicity determined in vitro on osteoblasts, osteoclasts and osteoarthritic chondrocytes. The synthesized Ag-NP can be incorporated as additive of biomaterials or pharmaceutical products to confer antimicrobial activity in a powdered form in different formulations, dispersed in

  20. Nuclear Quantum Effects in the Dynamics of Biologically Relevant Systems from First Principles

    NASA Astrophysics Data System (ADS)

    Rossi, Mariana; Fang, Wei; Michaelides, Angelos

    Understanding the structure and dynamics of biomolecules is crucial for unveiling the physics behind biology-related processes. These molecules are very flexible and stabilized by a delicate balance of weak (quantum) interactions, thus requiring the inclusion of anharmonic entropic contributions and an accurate description of the electronic and nuclear structure from quantum mechanics. We here join state of the art density-functional theory (DFT) and path integral molecular dynamics (PIMD) to gain quantitative insight into biologically relevant systems. Our design of a better and more efficient approximation to quantum time correlation functions based on PIMD (TRPMD) enables the calculation of ab initio TCFs with which we calculate IR/vibrational spectra and diffusion coefficients. In stacked polyglutamine strands (structures often related to amyloid diseases) a combination of NQE and H-bond cooperativity provides a small free energy stabilization that we connect to a softening of high frequency modes, enhanced by nuclear quantum anharmonicity [3].

  1. [Microbiological and biological methods of the European Pharmacopoeia. Relevant for each medicinal product].

    PubMed

    Norwig, J

    2014-10-01

    According to the EU Directive 2001/83 the European Pharmacopoeia is the official Pharmacopoeia of the European Union. Therefore the European Pharmacopoeia is one of the legal pharmacopoeial compendia in Germany. Any licensed medicinal product on the German market complies with the requirements of the compendial monographs, if applicable. Because the general monographs of the European Pharmacopoeia on Dosage Forms, Substances for Pharmaceutical Use and Pharmaceutical Preparations refer to the microbiological and biological methods of the Pharmacopoeia, the methods are relevant for medicinal products, too. This article presents a rough summary of the microbiological and biological methods of the European Pharmacopoeia and is intended to be a stimulus for the reader to better understand the original compendia. The short description of the methods mentioned, here, is a summary from the Pharmacopoeia and the non-official collection of comments on the texts of the European Pharmacopoeia. PMID:25200487

  2. KDAC8 substrate specificity quantified by a biologically relevant, label-free deacetylation assay.

    PubMed

    Toro, Tasha B; Watt, Terry J

    2015-12-01

    Analysis of the human proteome has identified thousands of unique protein sequences that contain acetylated lysine residues in vivo. These modifications regulate a variety of biological processes and are reversed by the lysine deacetylase (KDAC) family of enzymes. Despite the known prevalence and importance of acetylation, the details of KDAC substrate recognition are not well understood. While several methods have been developed to monitor protein deacetylation, none are particularly suited for identifying enzyme-substrate pairs of label-free substrates across the entire family of lysine deacetylases. Here, we present a fluorescamine-based assay which is more biologically relevant than existing methods and amenable to probing substrate specificity. Using this assay, we evaluated the activity of KDAC8 and other lysine deacetylases, including a sirtuin, for several peptides derived from known acetylated proteins. KDAC8 showed clear preferences for some peptides over others, indicating that the residues immediately surrounding the acetylated lysine play an important role in substrate specificity. Steady-state kinetics suggest that the sequence surrounding the acetylated lysine affects binding affinity and catalytic rate independently. Our results provide direct evidence that potential KDAC8 substrates previously identified through cell based experiments can be directly deacetylated by KDAC8. Conversely, the data from this assay did not correlate well with predictions from previous screens for KDAC8 substrates using less biologically relevant substrates and assay conditions. Combining results from our assay with mass spectrometry-based experiments and cell-based experiments will allow the identification of specific KDAC-substrate pairs and lead to a better understanding of the biological consequences of these interactions. PMID:26402585

  3. Metal based biologically active compounds: design, synthesis, and antibacterial/antifungal/cytotoxic properties of triazole-derived Schiff bases and their oxovanadium(IV) complexes.

    PubMed

    Chohan, Zahid H; Sumrra, Sajjad H; Youssoufi, Moulay H; Hadda, Taibi B

    2010-07-01

    A new series of oxovanadium(IV) complexes have been designed and synthesized with a new class of triazole Schiff bases derived from the reaction of 3,5-diamino-1,2,4-triazole with 2-hydroxy-1-naphthaldehyde, pyrrole-2-carboxaldehyde, pyridine-2-carboxaldehyde and acetyl pyridine-2-carboxaldehyde, respectively. Physical (magnetic susceptibility, molar conductance), spectral (IR, (1)H NMR, (13)C NMR, mass and electronic) and analytical data have established the structures of these synthesized Schiff bases and their oxovanadium(IV) complexes. The Schiff bases, predominantly act as bidentate and coordinate with the vanadium(IV) metal to give a stoichiometric ratio of 1:2 [M:L], forming a general formulae, [M(L-H)(2)] and [M(L)(2)]SO(4) where L = (L(1))-(L(4)) and M = VO(IV) of these complexes in a square-pyramidal geometry. In order to evaluate the biological activity of Schiff bases and to assess the role of vanadium(IV) metal on biological activity, the triazole Schiff bases and their oxovanadium(IV) complexes have been studied for in vitro antibacterial activity against four Gram-negative (Escherichia coli, Shigella flexenari, Pseudomonas aeruginosa, Salmonella typhi) and two Gram-positive (Staphylococcus aureus, Bacillus subtilis) bacterial strains, in vitro antifungal activity against Trichophyton longifucus, Candida albican, Aspergillus flavus, Microscopum canis, Fusarium solani and Candida glaberata. The simple Schiff bases showed weaker to significant activity against one or more bacterial and fungal strains. In most of the cases higher activity was exhibited upon coordination with vanadium(IV) metal. Brine shrimp bioassay was also carried out for in vitro cytotoxic properties against Artemia salina. PMID:20338672

  4. Inactivation of the antibacterial and cytotoxic properties of silver ions by biologically relevant compounds.

    PubMed

    Mulley, Geraldine; Jenkins, A Tobias A; Waterfield, Nicholas R

    2014-01-01

    There has been a recent surge in the use of silver as an antimicrobial agent in a wide range of domestic and clinical products, intended to prevent or treat bacterial infections and reduce bacterial colonization of surfaces. It has been reported that the antibacterial and cytotoxic properties of silver are affected by the assay conditions, particularly the type of growth media used in vitro. The toxicity of Ag+ to bacterial cells is comparable to that of human cells. We demonstrate that biologically relevant compounds such as glutathione, cysteine and human blood components significantly reduce the toxicity of silver ions to clinically relevant pathogenic bacteria and primary human dermal fibroblasts (skin cells). Bacteria are able to grow normally in the presence of silver nitrate at >20-fold the minimum inhibitory concentration (MIC) if Ag+ and thiols are added in a 1:1 ratio because the reaction of Ag+ with extracellular thiols prevents silver ions from interacting with cells. Extracellular thiols and human serum also significantly reduce the antimicrobial activity of silver wound dressings Aquacel-Ag (Convatec) and Acticoat (Smith & Nephew) to Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli in vitro. These results have important implications for the deployment of silver as an antimicrobial agent in environments exposed to biological tissue or secretions. Significant amounts of money and effort have been directed at the development of silver-coated medical devices (e.g. dressings, catheters, implants). We believe our findings are essential for the effective design and testing of antimicrobial silver coatings. PMID:24728271

  5. Inactivation of the Antibacterial and Cytotoxic Properties of Silver Ions by Biologically Relevant Compounds

    PubMed Central

    Mulley, Geraldine; Jenkins, A. Tobias A.; Waterfield, Nicholas R.

    2014-01-01

    There has been a recent surge in the use of silver as an antimicrobial agent in a wide range of domestic and clinical products, intended to prevent or treat bacterial infections and reduce bacterial colonization of surfaces. It has been reported that the antibacterial and cytotoxic properties of silver are affected by the assay conditions, particularly the type of growth media used in vitro. The toxicity of Ag+ to bacterial cells is comparable to that of human cells. We demonstrate that biologically relevant compounds such as glutathione, cysteine and human blood components significantly reduce the toxicity of silver ions to clinically relevant pathogenic bacteria and primary human dermal fibroblasts (skin cells). Bacteria are able to grow normally in the presence of silver nitrate at >20-fold the minimum inhibitory concentration (MIC) if Ag+ and thiols are added in a 1∶1 ratio because the reaction of Ag+ with extracellular thiols prevents silver ions from interacting with cells. Extracellular thiols and human serum also significantly reduce the antimicrobial activity of silver wound dressings Aquacel-Ag (Convatec) and Acticoat (Smith & Nephew) to Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli in vitro. These results have important implications for the deployment of silver as an antimicrobial agent in environments exposed to biological tissue or secretions. Significant amounts of money and effort have been directed at the development of silver-coated medical devices (e.g. dressings, catheters, implants). We believe our findings are essential for the effective design and testing of antimicrobial silver coatings. PMID:24728271

  6. DNA Hypomethylation Affects Cancer-Related Biological Functions and Genes Relevant in Neuroblastoma Pathogenesis

    PubMed Central

    Mayol, Gemma; Martín-Subero, José I.; Ríos, José; Queiros, Ana; Kulis, Marta; Suñol, Mariona; Esteller, Manel; Gómez, Soledad; Garcia, Idoia; de Torres, Carmen; Rodríguez, Eva; Galván, Patricia; Mora, Jaume; Lavarino, Cinzia

    2012-01-01

    Neuroblastoma (NB) pathogenesis has been reported to be closely associated with numerous genetic alterations. However, underlying DNA methylation patterns have not been extensively studied in this developmental malignancy. Here, we generated microarray-based DNA methylation profiles of primary neuroblastic tumors. Stringent supervised differential methylation analyses allowed us to identify epigenetic changes characteristic for NB tumors as well as for clinical and biological subtypes of NB. We observed that gene-specific loss of DNA methylation is more prevalent than promoter hypermethylation. Remarkably, such hypomethylation affected cancer-related biological functions and genes relevant to NB pathogenesis such as CCND1, SPRR3, BTC, EGF and FGF6. In particular, differential methylation in CCND1 affected mostly an evolutionary conserved functionally relevant 3′ untranslated region, suggesting that hypomethylation outside promoter regions may play a role in NB pathogenesis. Hypermethylation targeted genes involved in cell development and proliferation such as RASSF1A, POU2F2 or HOXD3, among others. The results derived from this study provide new candidate epigenetic biomarkers associated with NB as well as insights into the molecular pathogenesis of this tumor, which involves a marked gene-specific hypomethylation. PMID:23144874

  7. Biologically relevant molecular transducer with increased computing power and iterative abilities.

    PubMed

    Ratner, Tamar; Piran, Ron; Jonoska, Natasha; Keinan, Ehud

    2013-05-23

    As computing devices, which process data and interconvert information, transducers can encode new information and use their output for subsequent computing, offering high computational power that may be equivalent to a universal Turing machine. We report on an experimental DNA-based molecular transducer that computes iteratively and produces biologically relevant outputs. As a proof of concept, the transducer accomplished division of numbers by 3. The iterative power was demonstrated by a recursive application on an obtained output. This device reads plasmids as input and processes the information according to a predetermined algorithm, which is represented by molecular software. The device writes new information on the plasmid using hardware that comprises DNA-manipulating enzymes. The computation produces dual output: a quotient, represented by newly encoded DNA, and a remainder, represented by E. coli phenotypes. This device algorithmically manipulates genetic codes. PMID:23706637

  8. Lack of [3H]quinuclidinyl benzylate binding to biologically relevant binding sites on mononuclear cells.

    PubMed

    Adams, E M; Lubrano, T M; Gordon, J; Fields, J Z

    1992-09-01

    We analyzed the binding characteristics of [3H]quinuclidinyl benzylate ([3H]QNB), a muscarinic cholinergic ligand, to rat and human mononuclear cells (MNC). Under various assay conditions, atropine-sensitive, saturable binding occurred with an apparent Kd of 10 nM. Conditions which disrupted the MNC membrane reduced total binding and eliminated specific binding. Muscarinic agonists were unable to inhibit [3H]QNB binding to MNC at concentrations up to 10(-2) M. Stereoisomers dexetimide and levetimide were equipotent inhibitors of binding (IC50 2 x 10(-5) M). We conclude that, although atropine-sensitive binding of [3H]QNB to MNC occurs, the binding is not consistent with the presence of a biologically relevant muscarinic cholinergic receptor. PMID:1392105

  9. Biologically relevant photoacoustic imaging phantoms with tunable optical and acoustic properties.

    PubMed

    Vogt, William C; Jia, Congxian; Wear, Keith A; Garra, Brian S; Joshua Pfefer, T

    2016-10-01

    Established medical imaging technologies such as magnetic resonance imaging and computed tomography rely on well-validated tissue-simulating phantoms for standardized testing of device image quality. The availability of high-quality phantoms for optical-acoustic diagnostics such as photoacoustic tomography (PAT) will facilitate standardization and clinical translation of these emerging approaches. Materials used in prior PAT phantoms do not provide a suitable combination of long-term stability and realistic acoustic and optical properties. Therefore, we have investigated the use of custom polyvinyl chloride plastisol (PVCP) formulations for imaging phantoms and identified a dual-plasticizer approach that provides biologically relevant ranges of relevant properties. Speed of sound and acoustic attenuation were determined over a frequency range of 4 to 9 MHz and optical absorption and scattering over a wavelength range of 400 to 1100 nm. We present characterization of several PVCP formulations, including one designed to mimic breast tissue. This material is used to construct a phantom comprised of an array of cylindrical, hemoglobin-filled inclusions for evaluation of penetration depth. Measurements with a custom near-infrared PAT imager provide quantitative and qualitative comparisons of phantom and tissue images. Results indicate that our PVCP material is uniquely suitable for PAT system image quality evaluation and may provide a practical tool for device validation and intercomparison. PMID:26886681

  10. The ChEBI reference database and ontology for biologically relevant chemistry: enhancements for 2013.

    PubMed

    Hastings, Janna; de Matos, Paula; Dekker, Adriano; Ennis, Marcus; Harsha, Bhavana; Kale, Namrata; Muthukrishnan, Venkatesh; Owen, Gareth; Turner, Steve; Williams, Mark; Steinbeck, Christoph

    2013-01-01

    ChEBI (http://www.ebi.ac.uk/chebi) is a database and ontology of chemical entities of biological interest. Over the past few years, ChEBI has continued to grow steadily in content, and has added several new features. In addition to incorporating all user-requested compounds, our annotation efforts have emphasized immunology, natural products and metabolites in many species. All database entries are now 'is_a' classified within the ontology, meaning that all of the chemicals are available to semantic reasoning tools that harness the classification hierarchy. We have completely aligned the ontology with the Open Biomedical Ontologies (OBO) Foundry-recommended upper level Basic Formal Ontology. Furthermore, we have aligned our chemical classification with the classification of chemical-involving processes in the Gene Ontology (GO), and as a result of this effort, the majority of chemical-involving processes in GO are now defined in terms of the ChEBI entities that participate in them. This effort necessitated incorporating many additional biologically relevant compounds. We have incorporated additional data types including reference citations, and the species and component for metabolites. Finally, our website and web services have had several enhancements, most notably the provision of a dynamic new interactive graph-based ontology visualization. PMID:23180789

  11. Enhancement in dentin collagen’s biological stability after proanthocyanidins treatment in clinically relevant time periods

    PubMed Central

    Liu, Yi; Chen, Mingsheng; Yao, Xiaomei; Xu, Changqi; Zhang, Ying; Wang, Yong

    2013-01-01

    Objective To investigate whether proanthocyanidins (PA) is capable of improving dentin collagen’s biological stability through cross-linking within time periods that are clinically relevant. Materials and methods Demineralized dentin collagen slabs were treated with 3.75 wt% PA solution for 10 s, 1 min, 30 min, 60 min, 120 min, 360 min, and 720 min, respectively. The resultant cross-linked collagen samples were subject to digestion with 0.1% collagenase at 37 °C for 2 h, 6 h, 12 h, 24 h, 36 h, and 48 h. The percentage of weight loss after digestion was calculated to evaluate PA-treated collagen’s resistance toward enzymatic degradation. Fourier-Transformed Infrared (FTIR) spectroscopy was used to probe evidences of PA-collagen interactions after various periods of PA treatment. Results The collagenase digestion assay suggests that PA treatment as short as 10 s can enhance collagen’s resistance toward enzymatic challenge. The FTIR spectroscopy further verifies that PA is indeed incorporated into collagen regardless of treatment time, possibly via a mechanism involving the chemical interactions between PA and collagen. Significance This study confirmed that PA can effectively cross-link collagen and improve its biological stability in time periods as short as 10 s. The use of PA as a priming agent is therefore clinically feasible and is a promising approach to improving the durability of current dentin bonding systems. PMID:23434233

  12. Modelling low energy electron and positron tracks in biologically relevant media

    NASA Astrophysics Data System (ADS)

    Blanco, Francisco; Muñoz, Antonio; Almeida, Diogo; Ferreira da Silva, Filipe; Limão-Vieira, Paulo; Fuss, Martina C.; Sanz, Ana G.; García, Gustavo

    2013-09-01

    This colloquium describes an approach to incorporate into radiation damage models the effect of low and intermediate energy (0-100 eV) electrons and positrons, slowing down in biologically relevant materials (water and representative biomolecules). The core of the modelling procedure is a C++ computing programme named “Low Energy Particle Track Simulation (LEPTS)”, which is compatible with available general purpose Monte Carlo packages. Input parameters are carefully selected from theoretical and experimental cross section data and energy loss distribution functions. Data sources used for this purpose are reviewed showing examples of electron and positron cross section and energy loss data for interactions with different media of increasing complexity: atoms, molecules, clusters and condense matter. Finally, we show how such a model can be used to develop an effective dosimetric tool at the molecular level (i.e. nanodosimetry). Recent experimental developments to study the fragmentation induced in biologically material by charge transfer from neutrals and negative ions are also included.

  13. Comparative Analysis of Biologically Relevant Response Curves in Gene Expression Experiments: Heteromorphy, Heterochrony, and Heterometry

    PubMed Central

    Baker, Stuart G.

    2014-01-01

    To gain biological insights, investigators sometimes compare sequences of gene expression measurements under two scenarios (such as two drugs or species). For this situation, we developed an algorithm to fit, identify, and compare biologically relevant response curves in terms of heteromorphy (different curves), heterochrony (different transition times), and heterometry (different magnitudes). The curves are flat, linear, sigmoid, hockey-stick (sigmoid missing a steady state), transient (sigmoid missing two steady states), impulse (with peak or trough), step (with intermediate-level plateau), impulse+ (impulse with an extra parameter), step+ (step with an extra parameter), further characterized by upward or downward trend. To reduce overfitting, we fit the curves to every other response, evaluated the fit in the remaining responses, and identified the most parsimonious curves that yielded a good fit. We measured goodness of fit using a statistic comparable over different genes, namely the square root of the mean squared prediction error as a percentage of the range of responses, which we call the relative prediction error (RPE). We illustrated the algorithm using data on gene expression at 14 times in the embryonic development in two species of frogs. Software written in Mathematica is freely available.

  14. Design and synthesis of artificial glycopolypeptides as mediators of biologically relevant binding events

    NASA Astrophysics Data System (ADS)

    Polizzotti, Brian D.

    Toxins and pathogens achieve highly efficient and selective binding through multivalent interactions between relevant oligosaccharides and saccharide receptors on each toxin/pathogen subunit. Because of the important role played by protein-carbohydrate interactions in these pathogenic events and in other human diseases, considerable effort has been devoted toward the development of high-affinity ligands for carbohydrate binding proteins. Multivalent ligands synthesized via traditional polymer techniques have provided valuable insight as to the general guidelines that govern these multivalent interactions, but are inherently limited by an inability to effectively control the molecular weight, polydispersity, sequence, and/or geometrical placement of the saccharide moiety on the glycopolymer. This lack of control makes it virtually impossible to determine the origins of increased binding activity. The synthesis of polymers via protein engineering methods allows control over the molecular weight, as well as the number and spacing of saccharides on a scaffold, which permits the structure-based design of polypeptide-based polymers for inhibition of such multivalent binding events. As such, we have employed a combination of protein engineering techniques and chemical methods to produce a family of galactose-functionalized glycopolymers with different backbone compositions and architectures in which the density, saccharide spacing, and linker length of the pendent carbohydrate moieties have been varied. Such ligands may disrupt pathological carbohydrate-mediated recognition and act as a fundamentally new class of noncytotoxic therapeutic agents with broad applicability to a wide range of human disease; in addition, investigations like these will aid in the deconvolution of the impact of multivalency, spacing, and backbone rigidity in a variety of biologically relevant binding events.

  15. Semi-Supervised Multimodal Relevance Vector Regression Improves Cognitive Performance Estimation from Imaging and Biological Biomarkers

    PubMed Central

    Cheng, Bo; Chen, Songcan; Kaufer, Daniel I.

    2013-01-01

    Accurate estimation of cognitive scores for patients can help track the progress of neurological diseases. In this paper, we present a novel semi-supervised multimodal relevance vector regression (SM-RVR) method for predicting clinical scores of neurological diseases from multimodal imaging and biological biomarker, to help evaluate pathological stage and predict progression of diseases, e.g., Alzheimer’s diseases (AD). Unlike most existing methods, we predict clinical scores from multimodal (imaging and biological) biomarkers, including MRI, FDG-PET, and CSF. Considering that the clinical scores of mild cognitive impairment (MCI) subjects are often less stable compared to those of AD and normal control (NC) subjects due to the heterogeneity of MCI, we use only the multimodal data of MCI subjects, but no corresponding clinical scores, to train a semi-supervised model for enhancing the estimation of clinical scores for AD and NC subjects. We also develop a new strategy for selecting the most informative MCI subjects. We evaluate the performance of our approach on 202 subjects with all three modalities of data (MRI, FDG-PET and CSF) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The experimental results show that our SM-RVR method achieves a root-mean-square error (RMSE) of 1.91 and a correlation coefficient (CORR) of 0.80 for estimating the MMSE scores, and also a RMSE of 4.45 and a CORR of 0.78 for estimating the ADAS-Cog scores, demonstrating very promising performances in AD studies. PMID:23504659

  16. Investigation of some biologically relevant redox reactions using electrochemical mass spectrometry interfaced by desorption electrospray ionization

    PubMed Central

    Lu, Mei; Wolff, Chloe; Cui, Weidong

    2013-01-01

    Recently we have shown that, as a versatile ionization technique, desorption electrospray ionization (DESI) can serve as a useful interface to combine electrochemistry (EC) with mass spectrometry (MS). In this study, the EC/DESI-MS method has been further applied to investigate some aqueous phase redox reactions of biological significance, including the reduction of peptide disulfide bonds and nitroaromatics as well as the oxidation of phenothiazines. It was found that knotted/enclosed disulfide bonds in the peptides apamin and endothelin could be electrochemically cleaved. Subsequent tandem MS analysis of the resulting reduced peptide ions using collision-induced dissociation (CID) and electron-capture dissociation (ECD) gave rise to extensive fragment ions, providing a fast protocol for sequencing peptides with complicated disulfide bond linkages. Flunitrazepam and clonazepam, a class of nitroaromatic drugs, are known to undergo reduction into amines which was proposed to involve nitroso and N-hydroxyl intermediates. Now in this study, these corresponding intermediate ions were successfully intercepted and their structures were confirmed by CID. This provides mass spectrometric evidence for the mechanism of the nitro to amine conversion process during nitroreduction, an important redox reaction involved in carcinogenesis. In addition, the well-known oxidation reaction of chlorpromazine was also examined. The putative transient one-electron transfer product, the chlorpromazine radical cation (m/z 318), was captured by MS, for the first time, and its structure was also verified by CID. In addition to these observations, some features of the DESI-interfaced electrochemical mass spectrometry were discussed, such as simple instrumentation and the lack of background signal. These results further demonstrate the feasibility of EC/DESI-MS for the study of the biology-relevant redox chemistry and would find applications in proteomics and drug development research. PMID

  17. Semi-supervised multimodal relevance vector regression improves cognitive performance estimation from imaging and biological biomarkers.

    PubMed

    Cheng, Bo; Zhang, Daoqiang; Chen, Songcan; Kaufer, Daniel I; Shen, Dinggang

    2013-07-01

    Accurate estimation of cognitive scores for patients can help track the progress of neurological diseases. In this paper, we present a novel semi-supervised multimodal relevance vector regression (SM-RVR) method for predicting clinical scores of neurological diseases from multimodal imaging and biological biomarker, to help evaluate pathological stage and predict progression of diseases, e.g., Alzheimer's diseases (AD). Unlike most existing methods, we predict clinical scores from multimodal (imaging and biological) biomarkers, including MRI, FDG-PET, and CSF. Considering that the clinical scores of mild cognitive impairment (MCI) subjects are often less stable compared to those of AD and normal control (NC) subjects due to the heterogeneity of MCI, we use only the multimodal data of MCI subjects, but no corresponding clinical scores, to train a semi-supervised model for enhancing the estimation of clinical scores for AD and NC subjects. We also develop a new strategy for selecting the most informative MCI subjects. We evaluate the performance of our approach on 202 subjects with all three modalities of data (MRI, FDG-PET and CSF) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The experimental results show that our SM-RVR method achieves a root-mean-square error (RMSE) of 1.91 and a correlation coefficient (CORR) of 0.80 for estimating the MMSE scores, and also a RMSE of 4.45 and a CORR of 0.78 for estimating the ADAS-Cog scores, demonstrating very promising performances in AD studies. PMID:23504659

  18. A Comparison of Biological and Adoptive Mothers and Fathers: The Relevance of Biological Kinship and Gendered Constructs of Parenthood.

    ERIC Educational Resources Information Center

    Miall, Charlene E.; March, Karen

    2003-01-01

    Used qualitative interviews to examine beliefs and values about biological and adoptive parents. Considered how biological kinship, gender, and actual parenting behavior affect the assessments respondents made of the emotional bonding between parents and children. Found that biological and adoptive parents viewed motherhood as instinctive and…

  19. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

    PubMed

    Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H; Johnson, Andrew D; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B; Nolte, Ilja M; van der Most, Peter J; Wright, Alan F; Shuldiner, Alan R; Morrison, Alanna C; Hofman, Albert; Smith, Albert V; Dreisbach, Albert W; Franke, Andre; Uitterlinden, Andre G; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I; Ponte, Belen; Oostra, Ben A; Paulweber, Bernhard; Krämer, Bernhard K; Mitchell, Braxton D; Buckley, Brendan M; Peralta, Carmen A; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N; Shaffer, Christian M; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J; Holliday, Elizabeth G; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B; Navis, Gerjan J; Curhan, Gary C; Ehret, George B; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K; Kramer, Holly; Lin, Honghuang; Leach, I Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M; Kolcic, Ivana; Persico, Ivana; Jukema, J Wouter; Wilson, James F; Felix, Janine F; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M; Gaspoz, Jean-Michel; Smith, Jennifer A; Faul, Jessica D; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N; Attia, John; Whitfield, John B; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C; Karjalainen, Juha; Fernandes, Jyotika K; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L; Lohman, Kurt; Portas, Laura; Launer, Lenore J; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K; Sale, Michele M; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B; Ridker, Paul M; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H; Kovacs, Peter; Wild, Philipp S; Froguel, Philippe; Rettig, Rainer; Mägi, Reedik; Biffar, Reiner; Schmidt, Reinhold; Middelberg, Rita P S; Carroll, Robert J; Penninx, Brenda W; Scott, Rodney J; Katz, Ronit; Sedaghat, Sanaz; Wild, Sarah H; Kardia, Sharon L R; Ulivi, Sheila; Hwang, Shih-Jen; Enroth, Stefan; Kloiber, Stefan; Trompet, Stella; Stengel, Benedicte; Hancock, Stephen J; Turner, Stephen T; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Zeller, Tanja; Zemunik, Tatijana; Lehtimäki, Terho; Illig, Thomas; Aspelund, Thor; Nikopensius, Tiit; Esko, Tonu; Tanaka, Toshiko; Gyllensten, Ulf; Völker, Uwe; Emilsson, Valur; Vitart, Veronique; Aalto, Ville; Gudnason, Vilmundur; Chouraki, Vincent; Chen, Wei-Min; Igl, Wilmar; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Loos, Ruth J F; Liu, Yongmei; Snieder, Harold; Pramstaller, Peter P; Parsa, Afshin; O'Connell, Jeffrey R; Susztak, Katalin; Hamet, Pavel; Tremblay, Johanne; de Boer, Ian H; Böger, Carsten A; Goessling, Wolfram; Chasman, Daniel I; Köttgen, Anna; Kao, W H Linda; Fox, Caroline S

    2016-01-01

    Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. PMID:26831199

  20. Relevant uses of surface proteins – display on self‐organized biological structures

    PubMed Central

    Jahns, Anika C.; Rehm, Bernd H. A.

    2012-01-01

    Summary Proteins are often found attached to surfaces of self‐assembling biological units such as whole microbial cells or subcellular structures, e.g. intracellular inclusions. In the last two decades surface proteins were identified that could serve as anchors for the display of foreign protein functions. Extensive protein engineering based on structure–function data enabled efficient display of technically and/or medically relevant protein functions. Small size, diversity of the anchor protein as well as support structure, genetic manipulability and controlled cultivation of phages, bacterial cells and yeasts contributed to the establishment of designed and specifically functionalized tools for applications as sensors, catalysis, biomedicine, vaccine development and library‐based screening technologies. Traditionally, phage display is employed for library screening but applications in biomedicine and vaccine development are also perceived. For some diagnostic purposes phages are even too small in size so other carrier materials where needed and gave way for cell and yeast display. Only recently, intracellular inclusions such as magnetosomes, polyhydroxyalkanoate granules and lipid bodies were conceived as stable subcellular structures enabling the display of foreign protein functions and showing potential as specific and tailor‐made devices for medical and biotechnological applications. PMID:21906264

  1. Action video game players' visual search advantage extends to biologically relevant stimuli.

    PubMed

    Chisholm, Joseph D; Kingstone, Alan

    2015-07-01

    Research investigating the effects of action video game experience on cognition has demonstrated a host of performance improvements on a variety of basic tasks. Given the prevailing evidence that these benefits result from efficient control of attentional processes, there has been growing interest in using action video games as a general tool to enhance everyday attentional control. However, to date, there is little evidence indicating that the benefits of action video game playing scale up to complex settings with socially meaningful stimuli - one of the fundamental components of our natural environment. The present experiment compared action video game player (AVGP) and non-video game player (NVGP) performance on an oculomotor capture task that presented participants with face stimuli. In addition, the expression of a distractor face was manipulated to assess if action video game experience modulated the effect of emotion. Results indicate that AVGPs experience less oculomotor capture than NVGPs; an effect that was not influenced by the emotional content depicted by distractor faces. It is noteworthy that this AVGP advantage emerged despite participants being unaware that the investigation had to do with video game playing, and participants being equivalent in their motivation and treatment of the task as a game. The results align with the notion that action video game experience is associated with superior attentional and oculomotor control, and provides evidence that these benefits can generalize to more complex and biologically relevant stimuli. PMID:26071923

  2. Discrimination between biologically relevant calcium phosphate phases by surface-analytical techniques

    NASA Astrophysics Data System (ADS)

    Kleine-Boymann, Matthias; Rohnke, Marcus; Henss, Anja; Peppler, Klaus; Sann, Joachim; Janek, Juergen

    2014-08-01

    The spatially resolved phase identification of biologically relevant calcium phosphate phases (CPPs) in bone tissue is essential for the elucidation of bone remodeling mechanisms and for the diagnosis of bone diseases. Analytical methods with high spatial resolution for the discrimination between chemically quite close phases are rare. Therefore the applicability of state-of-the-art ToF-SIMS, XPS and EDX as chemically specific techniques was investigated. The eight CPPs hydroxyapatite (HAP), β-tricalcium phosphate (β-TCP), α-tricalcium phosphate (α-TCP), octacalcium phosphate (OCP), dicalcium phosphate dihydrate (DCPD), dicalcium phosphate (DCP), monocalcium phosphate (MCP) and amorphous calcium phosphate (ACP) were either commercial materials in high purity or synthesized by ourselves. The phase purity was proven by XRD analysis. All of the eight CPPs show different mass spectra and the phases can be discriminated by applying the principal component analysis method to the mass spectrometric data. The Ca/P ratios of all phosphates were determined by XPS and EDX. With both methods some CPPs can be distinguished, but the obtained Ca/P ratios deviate systematically from their theoretical values. It is necessary in any case to determine a calibration curve, respectively the ZAF values, from appropriate standards. In XPS also the O(1s)-satellite signals are correlated to the CPPs composition. Angle resolved and long-term XPS measurements of HAP clearly prove that there is no phosphate excess at the surface. Decomposition due to X-ray irradiation has not been observed.

  3. Multiple mechanisms for critical behavior in the biologically relevant phase of lecithin bilayers

    NASA Astrophysics Data System (ADS)

    Nagle, John F.; Petrache, Horia I.; Gouliaev, Nikolai; Tristram-Nagle, Stephanie; Liu, Yufeng; Suter, Robert M.; Gawrisch, Klaus

    1998-12-01

    Lipid bilayer membranes manifest critical behavior in the lamellar D spacing observed by x-ray and neutron diffraction as the main phase transition is approached from the biologically relevant high temperature phase. The freezing out of conformational disorder of the hydrocarbon chains drives the main transition, but how this causes critical behavior of D(T) has been an interesting puzzle and various models are under investigation. This paper presents x-ray scattering and NMR data to test the various models. One model involves the straightforward lengthening of hydrocarbon chains as TM is approached, but it is shown that this accounts only for about half the anomalous increase in D. Another model of fluctuation induced expansion of the water region is shown to be inconsistent with two kinds of data. The first inconsistency is the lack of an increase in the Caillé fluctuation parameter η1. The second inconsistency is with D(T) data taken under osmotic pressure. Accurate simulations are employed to predict the theoretical values. A third model considers that the water spacing could expand because other interactions between bilayers may change as TM is approached, but there is no quantitative support for this model at present. A fourth model involving expansion of the headgroup region is tested with NMR data; results are qualitatively consistent but quantitatively inconclusive. While the precise mixture of models is still unresolved, it is concluded that multiple mechanisms must be operating in this critical regime.

  4. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

    PubMed Central

    Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y.; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H.; Johnson, Andrew D.; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F.; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B.; Nolte, Ilja M.; van der Most, Peter J.; Wright, Alan F.; Shuldiner, Alan R.; Morrison, Alanna C.; Hofman, Albert; Smith, Albert V.; Dreisbach, Albert W.; Franke, Andre; Uitterlinden, Andre G.; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I.; Ponte, Belen; Oostra, Ben A.; Paulweber, Bernhard; Krämer, Bernhard K.; Mitchell, Braxton D.; Buckley, Brendan M.; Peralta, Carmen A.; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N.; Shaffer, Christian M.; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M.; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S.; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J.; Holliday, Elizabeth G.; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P.; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B.; Navis, Gerjan J.; Curhan, Gary C.; Ehret, George B.; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W.; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K.; Kramer, Holly; Lin, Honghuang; Leach, I. Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M.; Kolcic, Ivana; Persico, Ivana; Jukema, J. Wouter; Wilson, James F.; Felix, Janine F.; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M.; Gaspoz, Jean-Michel; Smith, Jennifer A.; Faul, Jessica D.; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N.; Attia, John; Whitfield, John B.; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C.; Karjalainen, Juha; Fernandes, Jyotika K.; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L.; Lohman, Kurt; Portas, Laura; Launer, Lenore J.; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M.; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E.; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C.; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A.; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K.; Sale, Michele M.; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G.; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H.; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B.; Ridker, Paul M.; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H.; Abecasis, Goncalo R.; Adair, Linda S.; Alexander, Myriam; Altshuler, David; Amin, Najaf; Arking, Dan E.; Arora, Pankaj; Aulchenko, Yurii; Bakker, Stephan J. L.; Bandinelli, Stefania; Barroso, Ines; Beckmann, Jacques S.; Beilby, John P.; Bergman, Richard N.; Bergmann, Sven; Bis, Joshua C.; Boehnke, Michael; Bonnycastle, Lori L.; Bornstein, Stefan R.; Bots, Michiel L.; Bragg-Gresham, Jennifer L.; Brand, Stefan-Martin; Brand, Eva; Braund, Peter S.; Brown, Morris J.; Burton, Paul R.; Casas, Juan P.; Caulfield, Mark J.; Chakravarti, Aravinda; Chambers, John C.; Chandak, Giriraj R.; Chang, Yen-Pei C.; Charchar, Fadi J.; Chaturvedi, Nish; Shin Cho, Yoon; Clarke, Robert; Collins, Francis S.; Collins, Rory; Connell, John M.; Cooper, Jackie A.; Cooper, Matthew N.; Cooper, Richard S.; Corsi, Anna Maria; Dörr, Marcus; Dahgam, Santosh; Danesh, John; Smith, George Davey; Day, Ian N. M.; Deloukas, Panos; Denniff, Matthew; Dominiczak, Anna F.; Dong, Yanbin; Doumatey, Ayo; Elliott, Paul; Elosua, Roberto; Erdmann, Jeanette; Eyheramendy, Susana; Farrall, Martin; Fava, Cristiano; Forrester, Terrence; Fowkes, F. Gerald R.; Fox, Ervin R.; Frayling, Timothy M.; Galan, Pilar

    2016-01-01

    Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. PMID:26831199

  5. Development of a biologically relevant calcium phosphate substrate for sum frequency generation vibrational spectroscopy.

    PubMed

    McGall, Sarah J; Davies, Paul B; Neivandt, David J

    2005-10-01

    A novel biologically relevant composite substrate has been prepared consisting of a calcium phosphate (CaP) layer formed by magnetron sputter-coating from a hydroxyapatite (HA) target onto a gold-coated silicon substrate. The CaP layer is intended to mimic tooth and bone surfaces and allows polymers used in oral care to be deposited in a procedure analogous to that used for dental surfaces. The polymer cetyl dimethicone copolyol (CDC) was deposited onto the CaP surface of the substrate by Langmuir Blodgett deposition, and the structure of the adsorbed layer was investigated by the surface specific technique of sum frequency generation (SFG) vibrational spectroscopy. The gold sublayer provides enhancement of the SFG signal arising from the polymer but plays no part in the adsorption of the polymer. The surface morphology of the substrate was investigated using SEM and AFM. The surface roughness was commensurate with that of the thermally evaporated gold sublayer and uniform over areas of at least 36 mum(2). The chemical composition of the CaP-coated surface was determined by FTIR and TOF-SIMS. It was concluded that the surface is primarily calcium phosphate present as a mixture of amorphous, non-hydroxylated phases rather than solely stoichiometric hydroxyapatite. The SFG spectra from CDC on CaP were closely similar, both in resonance wavenumbers and in their relative intensities, with spectra of thin films of CDC recorded directly on gold. Application of previous analysis of the spectra of CDC on gold therefore enabled interpretation of the polymer orientation and conformation on the CaP substrate. PMID:16834276

  6. Epigenetic regulation of EFEMP1 in prostate cancer: biological relevance and clinical potential

    PubMed Central

    Almeida, Mafalda; Costa, Vera L; Costa, Natália R; Ramalho-Carvalho, João; Baptista, Tiago; Ribeiro, Franclim R; Paulo, Paula; Teixeira, Manuel R; Oliveira, Jorge; Lothe, Ragnhild A; Lind, Guro E; Henrique, Rui; Jerónimo, Carmen

    2014-01-01

    Epigenetic alterations are common in prostate cancer (PCa) and seem to contribute decisively to its initiation and progression. Moreover, aberrant promoter methylation is a promising biomarker for non-invasive screening. Herein, we sought to characterize EFEMP1 as biomarker for PCa, unveiling its biological relevance in prostate carcinogenesis. Microarray analyses of treated PCa cell lines and primary tissues enabled the selection of differentially methylated genes, among which EFEMP1 was further validated by MSP and bisulfite sequencing. Assessment of biomarker performance was accomplished by qMSP. Expression analysis of EFEMP1 and characterization of histone marks were performed in tissue samples and cancer cell lines to determine the impact of epigenetic mechanisms on EFEMP1 transcriptional regulation. Phenotypic assays, using transfected cell lines, permitted the evaluation of EFEMP1’s role in PCa development. EFEMP1 methylation assay discriminated PCa from normal prostate tissue (NPT; P < 0.001, Kruskall–Wallis test) and renal and bladder cancers (96% sensitivity and 98% specificity). EFEMP1 transcription levels inversely correlated with promoter methylation and histone deacetylation, suggesting that both epigenetic mechanisms are involved in gene regulation. Phenotypic assays showed that EFEMP1 de novo expression reduces malignant phenotype of PCa cells. EFEMP1 promoter methylation is prevalent in PCa and accurately discriminates PCa from non-cancerous prostate tissues and other urological neoplasms. This epigenetic alteration occurs early in prostate carcinogenesis and, in association with histone deacetylation, progressively leads to gene down-regulation, fostering cell proliferation, invasion and evasion of apoptosis. PMID:25211630

  7. Dynamic clustering threshold reduces conformer ensemble size while maintaining a biologically relevant ensemble.

    PubMed

    Yongye, Austin B; Bender, Andreas; Martínez-Mayorga, Karina

    2010-08-01

    Representing the 3D structures of ligands in virtual screenings via multi-conformer ensembles can be computationally intensive, especially for compounds with a large number of rotatable bonds. Thus, reducing the size of multi-conformer databases and the number of query conformers, while simultaneously reproducing the bioactive conformer with good accuracy, is of crucial interest. While clustering and RMSD filtering methods are employed in existing conformer generators, the novelty of this work is the inclusion of a clustering scheme (NMRCLUST) that does not require a user-defined cut-off value. This algorithm simultaneously optimizes the number and the average spread of the clusters. Here we describe and test four inter-dependent approaches for selecting computer-generated conformers, namely: OMEGA, NMRCLUST, RMS filtering and averaged-RMS filtering. The bioactive conformations of 65 selected ligands were extracted from the corresponding protein:ligand complexes from the Protein Data Bank, including eight ligands that adopted dissimilar bound conformations within different receptors. We show that NMRCLUST can be employed to further filter OMEGA-generated conformers while maintaining biological relevance of the ensemble. It was observed that NMRCLUST (containing on average 10 times fewer conformers per compound) performed nearly as well as OMEGA, and both outperformed RMS filtering and averaged-RMS filtering in terms of identifying the bioactive conformations with excellent and good matches (0.5 < RMSD < 1.0 A). Furthermore, we propose thresholds for OMEGA root-mean square filtering depending on the number of rotors in a compound: 0.8, 1.0 and 1.4 for structures with low (1-4), medium (5-9) and high (10-15) numbers of rotatable bonds, respectively. The protocol employed is general and can be applied to reduce the number of conformers in multi-conformer compound collections and alleviate the complexity of downstream data processing in virtual screening experiments

  8. Solid-supported cross-metathesis and a formal alkane metathesis for the generation of biologically relevant molecules.

    PubMed

    Méndez, Luciana; Mata, Ernesto G

    2015-02-01

    Solid-phase synthetic strategies toward the generation of libraries of biologically relevant molecules were developed using olefin cross-metathesis as a key step. It is remarkably the formal alkane metathesis based on a one-pot, microwave-assisted, ruthenium-catalyzed cross-metathesis and reduction to obtain Csp3-Csp3 linkages. PMID:25569690

  9. Enhanced stability and local structure in biologically relevant amorphous materials containing pyrophosphate

    SciTech Connect

    Slater, Colin; Laurencin, Danielle; Burnell, Victoria; Smith, Mark E.; Grover, Liam M.; Hriljac, Joseph A.; Wright, Adrian J.

    2012-10-25

    There is increasing evidence that amorphous inorganic materials play a key role in biomineralisation in many organisms, however the inherent instability of synthetic analogues in the absence of the complex in vivo matrix limits their study and clinical exploitation. To address this, we report here an approach that enhances long-term stability to >1 year of biologically relevant amorphous metal phosphates, in the absence of any complex stabilizers, by utilizing pyrophosphates (P{sub 2}O{sub 7}{sup 4-}); species themselves ubiquitous in vivo. Ambient temperature precipitation reactions were employed to synthesise amorphous Ca{sub 2}P{sub 2}O{sub 7}.nH{sub 2}O and Sr{sub 2}P{sub 2}O{sub 7}.nH{sub 2}O (3.8 < n < 4.2) and their stability and structure were investigated. Pair distribution functions (PDF) derived from synchrotron X-ray data indicated a lack of structural order beyond 8 {angstrom} in both phases, with this local order found to resemble crystalline analogues. Further studies, including {sup 1}H and {sup 31}P solid state NMR, suggest the unusually high stability of these purely inorganic amorphous phases is partly due to disorder in the P-O-P bond angles within the P{sub 2}O{sub 7} units, which impede crystallization, and to water molecules, which are involved in H-bonds of various strengths within the structures and hamper the formation of an ordered network. In situ high temperature powder X-ray diffraction data indicated that the amorphous nature of both phases surprisingly persisted to 450 C. Further NMR and TGA studies found that above ambient temperature some water molecules reacted with P{sub 2}O{sub 7} anions, leading to the hydrolysis of some P-O-P linkages and the formation of HPO{sub 4}{sup 2-} anions within the amorphous matrix. The latter anions then recombined into P{sub 2}O{sub 7} ions at higher temperatures prior to crystallization. Together, these findings provide important new materials with unexplored potential for enzyme

  10. "Evo in the News:" Understanding Evolution and Students' Attitudes toward the Relevance of Evolutionary Biology

    ERIC Educational Resources Information Center

    Infanti, Lynn M.; Wiles, Jason R.

    2014-01-01

    This investigation evaluated the effects of exposure to the "Evo in the News" section of the "Understanding Evolution" website on students' attitudes toward biological evolution in undergraduates in a mixed-majors introductory biology course at Syracuse University. Students' attitudes toward evolution and changes therein were…

  11. CellBase, a comprehensive collection of RESTful web services for retrieving relevant biological information from heterogeneous sources

    PubMed Central

    Bleda, Marta; Tarraga, Joaquin; de Maria, Alejandro; Salavert, Francisco; Garcia-Alonso, Luz; Celma, Matilde; Martin, Ainoha; Dopazo, Joaquin; Medina, Ignacio

    2012-01-01

    During the past years, the advances in high-throughput technologies have produced an unprecedented growth in the number and size of repositories and databases storing relevant biological data. Today, there is more biological information than ever but, unfortunately, the current status of many of these repositories is far from being optimal. Some of the most common problems are that the information is spread out in many small databases; frequently there are different standards among repositories and some databases are no longer supported or they contain too specific and unconnected information. In addition, data size is increasingly becoming an obstacle when accessing or storing biological data. All these issues make very difficult to extract and integrate information from different sources, to analyze experiments or to access and query this information in a programmatic way. CellBase provides a solution to the growing necessity of integration by easing the access to biological data. CellBase implements a set of RESTful web services that query a centralized database containing the most relevant biological data sources. The database is hosted in our servers and is regularly updated. CellBase documentation can be found at http://docs.bioinfo.cipf.es/projects/cellbase. PMID:22693220

  12. Lateral Hypothalamus GABAergic Neurons Modulate Consummatory Behaviors Regardless of the Caloric Content or Biological Relevance of the Consumed Stimuli.

    PubMed

    Navarro, Montserrat; Olney, Jeffrey J; Burnham, Nathan W; Mazzone, Christopher M; Lowery-Gionta, Emily G; Pleil, Kristen E; Kash, Thomas L; Thiele, Todd E

    2016-05-01

    It was recently reported that activation of a subset of lateral hypothalamus (LH) GABAergic neurons induced both appetitive (food-seeking) and consummatory (eating) behaviors in vGat-ires-cre mice, while inhibition or deletion of GABAergic neurons blunted these behaviors. As food and caloric-dense liquid solutions were used, the data reported suggest that these LH GABAergic neurons may modulate behaviors that function to maintain homeostatic caloric balance. Here we report that chemogenetic activation of this GABAergic population in vGat-ires-cre mice increased consummatory behavior directed at any available stimulus, including those entailing calories (food, sucrose, and ethanol), those that do not (saccharin and water), and those lacking biological relevance (wood). Chemogenetic inhibition of these neurons attenuated consummatory behaviors. These data indicate that LH GABAergic neurons modulate consummatory behaviors regardless of the caloric content or biological relevance of the consumed stimuli. PMID:26442599

  13. Enhanced surface functionality via plasma modification and plasma deposition techniques to create more biologically relevant materials

    NASA Astrophysics Data System (ADS)

    Shearer, Jeffrey C.

    Functionalizing nanoparticles and other unusually shaped substrates to create more biologically relevant materials has become central to a wide range of research programs. One of the primary challenges in this field is creating highly functionalized surfaces without modifying the underlying bulk material. Traditional wet chemistry techniques utilize thin film depositions to functionalize nanomaterials with oxygen and nitrogen containing functional groups, such as --OH and --NHx. These functional groups can serve to create surfaces that are amenable to cell adhesion or can act as reactive groups for further attachment of larger structures, such as macromolecules or antiviral agents. Additional layers, such as SiO2, are often added between the nanomaterial and the functionalized coating to act as a barrier films, adhesion layers, and to increase overall hydrophilicity. However, some wet chemistry techniques can damage the bulk material during processing. This dissertation examines the use of plasma processing as an alternative method for producing these highly functionalized surfaces on nanoparticles and polymeric scaffolds through the use of plasma modification and plasma enhanced chemical vapor deposition techniques. Specifically, this dissertation will focus on (1) plasma deposition of SiO2 barrier films on nanoparticle substrates; (2) surface functionalization of amine and alcohol groups through (a) plasma co-polymerization and (b) plasma modification; and (3) the design and construction of plasma hardware to facilitate plasma processing of nanoparticles and polymeric scaffolds. The body of work presented herein first examines the fabrication of composite nanoparticles by plasma processing. SiOxC y and hexylamine films were coated onto TiO2 nanoparticles to demonstrate enhanced water dispersion properties. Continuous wave and pulsed allyl alcohol plasmas were used to produce highly functionalized Fe2 O3 supported nanoparticles. Specifically, film composition was

  14. Carboxylate-Assisted Iridium-Catalyzed C-H Amination of Arenes with Biologically Relevant Alkyl Azides.

    PubMed

    Zhang, Tao; Hu, Xuejiao; Wang, Zhen; Yang, Tiantian; Sun, Hao; Li, Guigen; Lu, Hongjian

    2016-02-24

    An iridium-catalyzed C-H amination of arenes with a wide substrate scope is reported. Benzamides with electron-donating and -withdrawing groups and linear, branched, and cyclic alkyl azides are all applicable. Cesium carboxylate is crucial for both reactivity and regioselectivity of the reactions. Many biologically relevant molecules, such as amino acid, peptide, steroid, sugar, and thymidine derivatives can be introduced to arenes with high yields and 100 % chiral retention. PMID:26712274

  15. Teleology then and now: the question of Kant's relevance for contemporary controversies over function in biology.

    PubMed

    Zammito, John

    2006-12-01

    'Naturalism' is the aspiration of contemporary philosophy of biology, and Kant simply cannot be refashioned into a naturalist. Instead, epistemological 'deflation' was the decisive feature of Kant's treatment of the 'biomedical' science in his day, so it is not surprising that this might attract some philosophers of science to him today. A certain sense of impasse in the contemporary 'function talk' seems to motivate renewed interest in Kant. Kant--drawing on his eighteenth-century predecessors-provided a discerning and powerful characterization of what biologists had to explain in organic form. His difference from the rest is that he opined that it was impossible to explain it. Its 'inscrutability' was intrinsic. The third Critique essentially proposed the reduction of biology to a kind of pre-scientific descriptivism, doomed never to attain authentic scientificity, to have its 'Newton of the blade of grass'. By contrast, for Locke, and a fortiori for Buffon and his followers, 'intrinsic purposiveness' was a fact of the matter about concrete biological phenomena; the features of internal self-regulation were hypotheses arising out of actual research practice. The difference comes most vividly to light once we recognize Kant's distinction of the concept of organism from the concept of life. If biology must conceptualize self-organization as actual in the world, Kant's regulative/constitutive distinction is pointless in practice and the (naturalist) philosophy of biology has urgent work to undertake for which Kant turns out not to be very helpful. PMID:17157770

  16. COMPARISON OF QUANTUM MECHANICAL METHODS TO COMPUTE THE BIOLOGICALLY RELEVANT REACTIVITIES OF CYCLOPENTA POLYCYCLIC AROMATIC HYDROCARBONS

    EPA Science Inventory

    In computational studies to understand the interaction of polycyclic aromatic hydrocarbons (PAHS) with biomolecular systems, the semi-empirical method AM1 has been used to determine the geometry of the PAH, its metabolites and relevant intermediates. umber of studies have shown t...

  17. Determination of the Biologically Relevant Sampling Depth for Terrestrial and Aquatic Ecological Risk Assessments (Final Report)

    EPA Science Inventory

    This technical paper provides defensible approximations for what the depth of the biologically active zone, or “biotic zone” is within certain environments. The methods used in this study differ somewhat between Part 1 (Terrestrial Biotic Zone) and Part 2 (Aquatic Biotic Zone). ...

  18. Soluble Epidermal Growth Factor Receptors (sEGFRs) in Cancer: Biological Aspects and Clinical Relevance.

    PubMed

    Maramotti, Sally; Paci, Massimiliano; Manzotti, Gloria; Rapicetta, Cristian; Gugnoni, Mila; Galeone, Carla; Cesario, Alfredo; Lococo, Filippo

    2016-01-01

    The identification of molecules that can reliably detect the presence of a tumor or predict its behavior is one of the biggest challenges of research in cancer biology. Biological fluids are intriguing mediums, containing many molecules that express the individual health status and, accordingly, may be useful in establishing the potential risk of cancer, defining differential diagnosis and prognosis, predicting the response to treatment, and monitoring the disease progression. The existence of circulating soluble growth factor receptors (sGFRs) deriving from their membrane counterparts has stimulated the interest of researchers to investigate the use of such molecules as potential cancer biomarkers. But what are the origins of circulating sGFRs? Are they naturally occurring molecules or tumor-derived products? Among these, the epidermal growth factor receptor (EGFR) is a cell-surface molecule significantly involved in cancer development and progression; it can be processed into biological active soluble isoforms (sEGFR). We have carried out an extensive review of the currently available literature on the sEGFRs and their mechanisms of regulation and biological function, with the intent to clarify the role of these molecules in cancer (and other pathological conditions) and, on the basis of the retrieved evidences, speculate about their potential use in the clinical setting. PMID:27104520

  19. Soluble Epidermal Growth Factor Receptors (sEGFRs) in Cancer: Biological Aspects and Clinical Relevance

    PubMed Central

    Maramotti, Sally; Paci, Massimiliano; Manzotti, Gloria; Rapicetta, Cristian; Gugnoni, Mila; Galeone, Carla; Cesario, Alfredo; Lococo, Filippo

    2016-01-01

    The identification of molecules that can reliably detect the presence of a tumor or predict its behavior is one of the biggest challenges of research in cancer biology. Biological fluids are intriguing mediums, containing many molecules that express the individual health status and, accordingly, may be useful in establishing the potential risk of cancer, defining differential diagnosis and prognosis, predicting the response to treatment, and monitoring the disease progression. The existence of circulating soluble growth factor receptors (sGFRs) deriving from their membrane counterparts has stimulated the interest of researchers to investigate the use of such molecules as potential cancer biomarkers. But what are the origins of circulating sGFRs? Are they naturally occurring molecules or tumor-derived products? Among these, the epidermal growth factor receptor (EGFR) is a cell-surface molecule significantly involved in cancer development and progression; it can be processed into biological active soluble isoforms (sEGFR). We have carried out an extensive review of the currently available literature on the sEGFRs and their mechanisms of regulation and biological function, with the intent to clarify the role of these molecules in cancer (and other pathological conditions) and, on the basis of the retrieved evidences, speculate about their potential use in the clinical setting. PMID:27104520

  20. Biologically relevant oxidants cause bound proteins to readily oxidatively cross-link at Guanine.

    PubMed

    Solivio, Morwena J; Nemera, Dessalegn B; Sallans, Larry; Merino, Edward J

    2012-02-20

    Oxidative DNA-protein cross-links have received less attention than other types of DNA damage and remain as one of the least understood types of oxidative lesion. A model system using ribonuclease A and a 27-nucleotide DNA was used to determine the propensity of oxidative cross-linking to occur in the presence of oxidants. Cross-link formation was examined using four different oxidation systems that generate singlet oxygen, superoxide, and metal-based Fenton reactions. It is shown that oxidative cross-linking occurs in yields ranging from 14% to a maximal yield of 61% in all oxidative systems when equivalent concentrations of DNA and protein are present. Because singlet oxygen is the most efficient oxidation system in generating DNA-protein cross-links, it was chosen for further analyses. Cross-linking occurred with single-stranded DNA binding protein and not with bovine serum albumin. Addition of salt lowered nonspecific binding affinity and lowered cross-link yield by up to 59%. The yield of cross-linking increased with increased ratios of protein compared with DNA. Cross-linking was highly dependent on the number of guanines in a DNA sequence. Loss of guanine content on the 27-nucleotide DNA led to nearly complete loss in cross-linking, while primer extension studies showed cross-links to predominantly occur at guanine base on a 100-nucleotide DNA. The chemical species generated were examined using two peptides derived from the ribonuclease A sequence, N-acetyl-AAAKF and N-acetyl-AYKTT, which were cross-linked to 2'-deoxyguanosine. The cross-link products were spiroiminodihydantoin, guanidinohydantoin, and tyrosyl-based adducts. Formation of tyrosine-based adducts may be competitive with the more well-studied lysine-based cross-links. We conclude that oxidative cross-links may be present at high levels in cells since the propensity to oxidatively cross-link is high and so much of the genomic DNA is coated with protein. PMID:22216745

  1. Biologically Relevant Mechanism For Catalytic Removal of Superoxide by Simple Manganese Compounds

    SciTech Connect

    Barnese K.; Cabelli D.; Gralla, E.B.; Valentine, J.S.

    2012-05-01

    Nonenzymatic manganese was first shown to provide protection against superoxide toxicity in vivo in 1981, but the chemical mechanism responsible for this protection subsequently became controversial due to conflicting reports concerning the ability of Mn to catalyze superoxide disproportionation in vitro. In a recent communication, we reported that low concentrations of a simple Mn phosphate salt under physiologically relevant conditions will indeed catalyze superoxide disproportionation in vitro. We report now that two of the four Mn complexes that are expected to be most abundant in vivo, Mn phosphate and Mn carbonate, can catalyze superoxide disproportionation at physiologically relevant concentrations and pH, whereas Mn pyrophosphate and citrate complexes cannot. Additionally, the chemical mechanisms of these reactions have been studied in detail, and the rates of reactions of the catalytic removal of superoxide by Mn phosphate and carbonate have been modeled. Physiologically relevant concentrations of these compounds were found to be sufficient to mimic an effective concentration of enzymatic superoxide dismutase found in vivo. This mechanism provides a likely explanation as to how Mn combats superoxide stress in cellular systems.

  2. multiClust: An R-package for Identifying Biologically Relevant Clusters in Cancer Transcriptome Profiles

    PubMed Central

    Lawlor, Nathan; Fabbri, Alec; Guan, Peiyong; George, Joshy; Karuturi, R. Krishna Murthy

    2016-01-01

    Clustering is carried out to identify patterns in transcriptomics profiles to determine clinically relevant subgroups of patients. Feature (gene) selection is a critical and an integral part of the process. Currently, there are many feature selection and clustering methods to identify the relevant genes and perform clustering of samples. However, choosing an appropriate methodology is difficult. In addition, extensive feature selection methods have not been supported by the available packages. Hence, we developed an integrative R-package called multiClust that allows researchers to experiment with the choice of combination of methods for gene selection and clustering with ease. Using multiClust, we identified the best performing clustering methodology in the context of clinical outcome. Our observations demonstrate that simple methods such as variance-based ranking perform well on the majority of data sets, provided that the appropriate number of genes is selected. However, different gene ranking and selection methods remain relevant as no methodology works for all studies. PMID:27330269

  3. Relevance of Crop Biology for Environmental Risk Assessment of Genetically Modified Crops in Africa.

    PubMed

    Akinbo, Olalekan; Hancock, James F; Makinde, Diran

    2015-01-01

    Knowledge about the crop biology of economic crops in Africa is needed for regulators to accurately review dossiers and conduct comprehensive environmental risk assessments (ERAs). This information allows regulators to decide whether biotech crops present a risk to biodiversity, since crossing between domesticated crops and their wild relatives could affect the adaptations of the wild species. The criteria that should be used in the evaluation of African crops for ERA include growth habit, center of origin, center of genetic diversity, proximity of wild relatives, inter-fertility, mode of pollen dispersal, length of pollen viability, mating system, invasiveness, weediness, mode of propagation, mode of seed dispersal, and length of seed dormancy. In this paper, we discuss the crops being genetic engineered in Africa and describe the crop biology of those with native relatives. PMID:26501055

  4. Inorganic concepts relevant to metal binding, activity, and toxicity in a biological system

    SciTech Connect

    Hoeschele, J.D. . Parke-Davis Pharmaceutical Research Div.); Turner, J.E.; England, M.W. )

    1990-01-01

    The purpose of this paper is to review selected physical and inorganic concepts and factors which might be important in assessing and/or understanding the fact and disposition of a metal system in a biological environment. Hopefully, such inquiries will ultimately permit us to understand, rationalize, and predict differences and trends in biological effects as a function of the basic nature of a metal system and, in optimal cases, serve as input to a system of guidelines for the notion of Chemical Dosimetry.'' The plan of this paper is to first review, in general terms, the basic principles of the Crystal Field Theory (CFT), a unifying theory of bonding in metal complexes. This will provide the necessary theoretical background for the subsequent discussion of selected concepts and factors. 21 refs., 7 figs., 6 tabs.

  5. Relevance of Crop Biology for Environmental Risk Assessment of Genetically Modified Crops in Africa

    PubMed Central

    Akinbo, Olalekan; Hancock, James F.; Makinde, Diran

    2015-01-01

    Knowledge about the crop biology of economic crops in Africa is needed for regulators to accurately review dossiers and conduct comprehensive environmental risk assessments (ERAs). This information allows regulators to decide whether biotech crops present a risk to biodiversity, since crossing between domesticated crops and their wild relatives could affect the adaptations of the wild species. The criteria that should be used in the evaluation of African crops for ERA include growth habit, center of origin, center of genetic diversity, proximity of wild relatives, inter-fertility, mode of pollen dispersal, length of pollen viability, mating system, invasiveness, weediness, mode of propagation, mode of seed dispersal, and length of seed dormancy. In this paper, we discuss the crops being genetic engineered in Africa and describe the crop biology of those with native relatives. PMID:26501055

  6. Consistent Robustness Analysis (CRA) Identifies Biologically Relevant Properties of Regulatory Network Models

    PubMed Central

    Saithong, Treenut; Painter, Kevin J.; Millar, Andrew J.

    2010-01-01

    Background A number of studies have previously demonstrated that “goodness of fit” is insufficient in reliably classifying the credibility of a biological model. Robustness and/or sensitivity analysis is commonly employed as a secondary method for evaluating the suitability of a particular model. The results of such analyses invariably depend on the particular parameter set tested, yet many parameter values for biological models are uncertain. Results Here, we propose a novel robustness analysis that aims to determine the “common robustness” of the model with multiple, biologically plausible parameter sets, rather than the local robustness for a particular parameter set. Our method is applied to two published models of the Arabidopsis circadian clock (the one-loop [1] and two-loop [2] models). The results reinforce current findings suggesting the greater reliability of the two-loop model and pinpoint the crucial role of TOC1 in the circadian network. Conclusions Consistent Robustness Analysis can indicate both the relative plausibility of different models and also the critical components and processes controlling each model. PMID:21179566

  7. Biologically relevant 3D tumor arrays: treatment response and the importance of stromal partners

    NASA Astrophysics Data System (ADS)

    Rizvi, Imran; Celli, Jonathan P.; Xu, Feng; Evans, Conor L.; Abu-Yousif, Adnan O.; Muzikansky, Alona; Elrington, Stefan A.; Pogue, Brian W.; Finkelstein, Dianne M.; Demirci, Utkan; Hasan, Tayyaba

    2011-02-01

    The development and translational potential of therapeutic strategies for cancer is limited, in part, by a lack of biological models that capture important aspects of tumor growth and treatment response. It is also becoming increasingly evident that no single treatment will be curative for this complex disease. Rationally-designed combination regimens that impact multiple targets provide the best hope of significantly improving clinical outcomes for cancer patients. Rapidly identifying treatments that cooperatively enhance treatment efficacy from the vast library of candidate interventions is not feasible, however, with current systems. There is a vital, unmet need to create cell-based research platforms that more accurately mimic the complex biology of human tumors than monolayer cultures, while providing the ability to screen therapeutic combinations more rapidly than animal models. We have developed a highly reproducible in vitro three-dimensional (3D) tumor model for micrometastatic ovarian cancer (OvCa), which in conjunction with quantitative image analysis routines to batch-process large datasets, serves as a high throughput reporter to screen rationally-designed combination regimens. We use this system to assess mechanism-based combination regimens with photodynamic therapy (PDT), which sensitizes OvCa to chemo and biologic agents, and has shown promise in clinic trials. We show that PDT synergistically enhances carboplatin efficacy in a sequence dependent manner. In printed heterocellular cultures we demonstrate that proximity of fibroblasts enhances 3D tumor growth and investigate co-cultures with endothelial cells. The principles described here could inform the design and evaluation of mechanism-based therapeutic options for a broad spectrum of metastatic solid tumors.

  8. The relevance and potential roles of microphysiological systems in biology and medicine

    PubMed Central

    Wikswo, John P.

    2014-01-01

    Microphysiological systems (MPS), consisting of interacting organs-on-chips or tissue-engineered, 3D organ constructs that use human cells, present an opportunity to bring new tools to biology, medicine, pharmacology, physiology, and toxicology. This issue of Experimental Biology and Medicine describes the ongoing development of MPS that can serve as in vitro models for bone and cartilage, brain, gastrointestinal tract, lung, liver, microvasculature, reproductive tract, skeletal muscle, and skin. Related topics addressed here are the interconnection of organs-on-chips to support physiologically based pharmacokinetics and drug discovery and screening, and the microscale technologies that regulate stem cell differentiation. The initial motivation for creating MPS was to increase the speed, efficiency, and safety of pharmaceutical development and testing, paying particular regard to the fact that neither monolayer monocultures of immortal or primary cell lines nor animal studies can adequately recapitulate the dynamics of drug-organ, drug-drug, and drug-organ-organ interactions in humans. Other applications include studies of the effect of environmental toxins on humans, identification, characterization, and neutralization of chemical and biological weapons, controlled studies of the microbiome and infectious disease that cannot be conducted in humans, controlled differentiation of induced pluripotent stem cells into specific adult cellular phenotypes, and studies of the dynamics of metabolism and signaling within and between human organs. The technical challenges are being addressed by many investigators, and in the process, it seems highly likely that significant progress will be made toward providing more physiologically realistic alternatives to monolayer monocultures or whole animal studies. The effectiveness of this effort will be determined in part by how easy the constructs are to use, how well they function, how accurately they recapitulate and report human

  9. Solid State Structures of Alkali Metal Ion Complexes Formed by Low-Molecular-Weight Ligands of Biological Relevance.

    PubMed

    Aoki, Katsuyuki; Murayama, Kazutaka; Hu, Ning-Hai

    2016-01-01

    This chapter provides structural data, mainly metal binding sites/modes, observed in crystal structures of alkali metal ion complexes containing low-molecular-weight ligands of biological relevance, mostly obtained from the Cambridge Structural Database (the CSD version 5.35 updated to February 2014). These ligands include (i) amino acids and small peptides, (ii) nucleic acid constituents (excluding quadruplexes and other oligonucleotides), (iii) simple carbohydrates, and (iv) naturally occurring antibiotic ionophores. For some representative complexes of these ligands, some details on the environment of the metal coordination and structural characteristics are described. PMID:26860299

  10. [Biological agents in animal breeding: an ancient but still relevant risk].

    PubMed

    Vellere, F; Cucchi, I; Somaruga, C; Brambilla, G; Colosio, C

    2012-01-01

    Agricultural activities expose workers to biological risk, due to the close contact that could occur with pathogens' reservoirs, such as soil, animals, manure and animal products. The paper describes factors that have contributed on the reduction or eradication of zoonoses, such as brucellosis, salmonellosis and bovine tuberculosis (monitoring and prevention of animal infectious diseases, industrialization and mechanization of agricultural activities), and on the other hand the emergence of new risks and new diseases (adaptability of microorganisms, generation of new strains, antibiotic resistance, dissemination of vectors). The role of Occupational Medicine in the prevention of zoonoses is discussed. PMID:23405674

  11. Rapid generation of biologically relevant hydrogels containing long-range chemical gradients **

    PubMed Central

    He, Jiankang; Du, Yanan; Villa-Uribe, Jose L; Hwang, Changmo; Li, Dichen

    2010-01-01

    Many biological processes are regulated by gradients of bioactive chemicals. Thus, the generation of materials with embedded chemical gradients may be beneficial for understanding biological phenomena and generating tissue-mimetic constructs. Here we describe a simple and versatile method to rapidly generate materials containing centimeter-long gradients of chemical properties in a microfluidic channel. The formation of chemical gradient was initiated by a passive-pump-induced forward flow and further developed during an evaporation-induced backward flow. The gradient was spatially controlled by the backward flow time and the hydrogel material containing the gradient was synthesized via photopolymerization. Gradients of a cell-adhesion ligand, Arg-Gly-Asp-Ser (RGDS), was incorporated in the poly(ethylene glycol)-diacrylate (PEG-DA) hydrogels to test the response of endothelial cells. The cells attached and spread along the hydrogel material in a manner consistent with the RGDS gradient profile. A hydrogel containing PEG-DA concentration gradient and constant RGDS concentration was also generated. The morphology of cells cultured on such hydrogel changed from round in the lower PEG-DA concentration regions to well-spread in the higher PEG-DA concentration regions. This approach is expected to be a valuable tool to investigate the cell-material interactions in a simple and high-throughput manner and to design graded biomimetic materials for tissue engineering applications. PMID:20216924

  12. Mammary Carcinogen-Protein Binding Potentials: Novel and Biologically Relevant Structure-Activity Relationship Model Descriptors

    PubMed Central

    Cunningham, A.R.; Qamar, S.; Carrasquer, C.A.; Holt, P.A.; Maguire, J.M.; Cunningham, S.L.; Trent, J.O.

    2010-01-01

    Previously, SAR models for carcinogenesis used descriptors that are essentially chemical descriptors. Herein we report the development of models with the cat-SAR expert system using biological descriptors (i.e., ligand-receptor interactions) rat mammary carcinogens. These new descriptors are derived from the virtual screening for ligand-receptor interactions of carcinogens, non-carcinogens, and mammary carcinogens to a set of 5494 target proteins. Leave-one-out validations of the ligand mammary carcinogen non-carcinogen model had a concordance between experimental and predicted results of 71% and the mammary carcinogen non-mammary carcinogen model was 72% concordant. The development of a hybrid fragment-ligand model improved the concordances to 85 and 83%, respectively. In a separate external validation exercise, hybrid fragment-ligand models had concordances of 81 and 76%. Analyses of example rat mammary carcinogens including the food mutagen and estrogenic compound PhIP, the herbicide atrazine, and the drug indomethacin, the ligand model identified a number of proteins associated with each compound that had previously been referenced in Medline in conjunction with the test chemical and separately with association to breast cancer. This new modelling approach can enhance model predictivity and help bridge the gap between chemical structure and carcinogenic activity by descriptors that are related to biological targets. PMID:20818582

  13. Recent advances in superhydrophobic surfaces and their relevance to biology and medicine.

    PubMed

    Ciasca, G; Papi, M; Businaro, L; Campi, G; Ortolani, M; Palmieri, V; Cedola, A; De Ninno, A; Gerardino, A; Maulucci, G; De Spirito, M

    2016-02-01

    By mimicking naturally occurring superhydrophobic surfaces, scientists can now realize artificial surfaces on which droplets of a few microliters of water are forced to assume an almost spherical shape and an extremely high contact angle. In recent decades, these surfaces have attracted much attention due to their technological applications for anti-wetting and self-cleaning materials. Very recently, researchers have shifted their interest to investigate whether superhydrophobic surfaces can be exploited to study biological systems. This research effort has stimulated the design and realization of new devices that allow us to actively organize, visualize and manipulate matter at both the microscale and nanoscale levels. Such precise control opens up wide applications in biomedicine, as it allows us to directly manipulate objects at the typical length scale of cells and macromolecules. This progress report focuses on recent biological and medical applications of superhydrophobicity. Particular regard is paid to those applications that involve the detection, manipulation and study of extremely small quantities of molecules, and to those that allow high throughput cell and biomaterial screening. PMID:26844980

  14. The relevance of nanoscale biological fragments for ice nucleation in clouds

    PubMed Central

    O′Sullivan, D.; Murray, B. J.; Ross, J. F.; Whale, T. F.; Price, H. C.; Atkinson, J. D.; Umo, N. S.; Webb, M. E.

    2015-01-01

    Most studies of the role of biological entities as atmospheric ice-nucleating particles have focused on relatively rare supermicron particles such as bacterial cells, fungal spores and pollen grains. However, it is not clear that there are sufficient numbers of these particles in the atmosphere to strongly influence clouds. Here we show that the ice-nucleating activity of a fungus from the ubiquitous genus Fusarium is related to the presence of nanometre-scale particles which are far more numerous, and therefore potentially far more important for cloud glaciation than whole intact spores or hyphae. In addition, we quantify the ice-nucleating activity of nano-ice nucleating particles (nano-INPs) washed off pollen and also show that nano-INPs are present in a soil sample. Based on these results, we suggest that there is a reservoir of biological nano-INPs present in the environment which may, for example, become aerosolised in association with fertile soil dust particles. PMID:25626414

  15. What Is Stochastic Resonance? Definitions, Misconceptions, Debates, and Its Relevance to Biology

    PubMed Central

    McDonnell, Mark D.; Abbott, Derek

    2009-01-01

    Stochastic resonance is said to be observed when increases in levels of unpredictable fluctuations—e.g., random noise—cause an increase in a metric of the quality of signal transmission or detection performance, rather than a decrease. This counterintuitive effect relies on system nonlinearities and on some parameter ranges being “suboptimal”. Stochastic resonance has been observed, quantified, and described in a plethora of physical and biological systems, including neurons. Being a topic of widespread multidisciplinary interest, the definition of stochastic resonance has evolved significantly over the last decade or so, leading to a number of debates, misunderstandings, and controversies. Perhaps the most important debate is whether the brain has evolved to utilize random noise in vivo, as part of the “neural code”. Surprisingly, this debate has been for the most part ignored by neuroscientists, despite much indirect evidence of a positive role for noise in the brain. We explore some of the reasons for this and argue why it would be more surprising if the brain did not exploit randomness provided by noise—via stochastic resonance or otherwise—than if it did. We also challenge neuroscientists and biologists, both computational and experimental, to embrace a very broad definition of stochastic resonance in terms of signal-processing “noise benefits”, and to devise experiments aimed at verifying that random variability can play a functional role in the brain, nervous system, or other areas of biology. PMID:19562010

  16. Collisions between low-energy electrons and small polyatomic targets of biological relevance

    NASA Astrophysics Data System (ADS)

    Hargreaves, Leigh

    2016-05-01

    Over the last decade, cross section measurements and calculations for DNA prototype molecules have received significant attention from the collisions community, due to the potential applications of this data in modelling electron transport through biological matter with a view to improving radiation dosimetry. Such data are additionally interesting from a fundamental aspect, as small carbon-based molecules are ideal targets for considering effects including target conformation, long-range dynamical interactions and coupling effects between the various degrees of freedom on the scattering properties of the target. At the California State University Fullerton, we have made a series of measurements of the elastic, vibrationally inelastic and electronically inelastic cross sections for a variety of small polyatomic targets, including water and the basic alcohols, ethylene, toluene and several fluorinated alkanes. These processes are important in a range of applications, primarily for modelling electron transport and thermalization, and energy deposition to a biological media. The data were obtained using a high resolution electron energy-loss spectrometer, operating in a crossed beam configuration with a moveable aperture gas source. The gas source design facilitates both an expedient and highly accurate method of removing background signal, and removes uncertainties from the data due to uncertainties in the beam profile. We have also performed scattering calculations employing the Schwinger Multichannel method, in collaboration with the California institute of technology, to compare with our measurements. In this talk, I will present an overview of our recent data and future research plans.

  17. The relevance of nanoscale biological fragments for ice nucleation in clouds

    NASA Astrophysics Data System (ADS)

    O‧Sullivan, D.; Murray, B. J.; Ross, J. F.; Whale, T. F.; Price, H. C.; Atkinson, J. D.; Umo, N. S.; Webb, M. E.

    2015-01-01

    Most studies of the role of biological entities as atmospheric ice-nucleating particles have focused on relatively rare supermicron particles such as bacterial cells, fungal spores and pollen grains. However, it is not clear that there are sufficient numbers of these particles in the atmosphere to strongly influence clouds. Here we show that the ice-nucleating activity of a fungus from the ubiquitous genus Fusarium is related to the presence of nanometre-scale particles which are far more numerous, and therefore potentially far more important for cloud glaciation than whole intact spores or hyphae. In addition, we quantify the ice-nucleating activity of nano-ice nucleating particles (nano-INPs) washed off pollen and also show that nano-INPs are present in a soil sample. Based on these results, we suggest that there is a reservoir of biological nano-INPs present in the environment which may, for example, become aerosolised in association with fertile soil dust particles.

  18. Advances in clarifying the phylogenetic relationships of acacias: Relevance for biological control

    NASA Astrophysics Data System (ADS)

    Kleinjan, C. A.; Hoffmann, J. H.

    2013-04-01

    Biological control of invasive Australian acacias will benefit from recent advances in resolving the phylogenetic relationships of Acacia s.l. and Acacia s.s. ("Australian acacias") within the subfamily Mimosoideae. Some of the phytophage taxa associated with Acacia s.s. display fidelity to a derived clade within the genus. This derived clade contains most of the Acacia s.s. species that have become problematic around the world. Phytophages that are demonstrably restricted to species within the derived clade pose essentially no risk to species outside Acacia s.s.. In contrast, prospective agents able to develop on species in the basal lineages of Acacia s.s. would require more-expansive testing because Acacia s.s. is closely related to the Ingeae, and then sequentially to the genera Acaciella, Mariosousa and Senegalia. Importantly, Vachellia is distantly related to Acacia s.s., being nested in basal Mimoseae lineages, and is thus less likely to be at risk than previously envisaged. Elucidation of these trends shows the benefits of having a comprehensive knowledge of the phylogeny of plants and phytophages under consideration for biological control.

  19. Catch bonds: physical models, structural bases, biological function and rheological relevance.

    PubMed

    Zhu, Cheng; Lou, Jizhong; McEver, Rodger P

    2005-01-01

    Force can shorten the lifetimes of macromolecular complexes (e.g., receptor-ligand bonds) by accelerating their dissociation. Perhaps paradoxical at first glance, bond lifetimes can also be prolonged by force. This counterintuitive behavior was named catch bonds, which is in contrast to the ordinary slip bonds that describe the intuitive behavior of lifetimes being shortened by force. Fifteen years after their theoretical proposal, catch bonds have finally been observed. In this article we review recently published data that have demonstrated catch bonds in the selectin system and suggested catch bonds in other systems, the theoretical models for their explanations, possible structural bases, their relation to flow-enhanced adhesion, and the potential biorheological relevance. PMID:16369083

  20. Solid state structures of cadmium complexes with relevance for biological systems.

    PubMed

    Carballo, Rosa; Castiñeiras, Alfonso; Domínguez-Martín, Alicia; García-Santos, Isabel; Niclós-Gutiérrez, Juan

    2013-01-01

    This chapter provides a review of the literature on structural information from crystal structures determined by X-ray diffractometry of cadmium(II) complexes containing ligands of potential biological interest. These ligands fall into three broad classes, (i) those containing N-donors such as purine or pyrimidine bases and derivatives of adenine, guanine or cytosine, (ii) those containing carboxylate groups such as α-amino acids, in particular the twenty essential ones, the water soluble vitamins (B-complex) or the polycarboxylates of EDTA type ligands, and (iii) S-donors such as thiols/thiolates or dithiocarbamates. A crystal and molecular structural analysis has been carried out for some representative complexes of these ligands, specifically addressing the coordination mode of ligands, the coordination environment of cadmium and, in some significant cases, the intermolecular interactions. PMID:23430774

  1. New Insights on the Biophysical Interaction of Resveratrol with Biomembrane Models: Relevance for Its Biological Effects.

    PubMed

    Neves, Ana Rute; Nunes, Cláudia; Reis, Salette

    2015-09-01

    Resveratrol has been widely studied because of its pleiotropic effects in cancer therapy, neuroprotection, and cardioprotection. It is believed that the interaction of resveratrol with biological membranes may play a key role in its therapeutic activity. The capacity of resveratrol to partition into lipid bilayers, its possible location within the membrane, and the influence of this compound on the membrane fluidity were investigated using membrane mimetic systems composed of egg l-α-phosphatidylcholine (EPC), cholesterol (CHOL), and sphingomyelin (SM). The results showed that resveratrol has greater affinity for the EPC bilayers than for EPC:CHOL [4:1] and EPC:CHOL:SM [1:1:1] membrane models. The increased difficulty in penetrating tight packed membranes is also demonstrated by fluorescence quenching of probes and by fluorescence anisotropy measurements. Resveratrol may be involved in the regulation of cell membrane fluidity, thereby contributing for cell homeostasis. PMID:26237152

  2. Biomechanical forces in the skeleton and their relevance to bone metastasis: biology and engineering considerations

    PubMed Central

    Lynch, Maureen; Fischbach, Claudia

    2014-01-01

    Bone metastasis represents the leading cause of breast cancer related-deaths. However, the effect of skeleton-associated biomechanical signals on the initiation, progression, and therapy response of breast cancer bone metastasis is largely unknown. This review seeks to highlight possible functional connections between skeletal mechanical signals and breast cancer bone metastasis and their contribution to clinical outcome. It provides an introduction to the physical and biological signals underlying bone functional adaptation and discusses the modulatory roles of mechanical loading and breast cancer metastasis in this process. Following a definition of biophysical design criteria, in vitro and in vivo approaches from the fields of bone biomechanics and tissue engineering will be reviewed that may be suitable to investigate breast cancer bone metastasis as a function of varied mechano-signaling. Finally, an outlook of future opportunities and challenges associated with this newly emerging field will be provided. PMID:25174311

  3. Biological relevance of oxidative debris present in as-prepared graphene oxide

    PubMed Central

    Pattammattel, Ajith; Williams, Christina L.; Pande, Paritosh; Tsui, William G.; Basu, Ashis K.

    2015-01-01

    The influence of oxidative debris (OD) present in as-prepared graphene oxide (GO) suspensions on proteins and its toxicity to human embryonic kidney cells (HEK-293T) are reported here. The OD was removed by repeated washing with aqueous ammonia to produce the corresponding base-washed GO (bwGO). The loading (w/w) of bovine serum albumin (BSA) was increased by 85% after base washing, whereas the loading of hemoglobin (Hb) and lysozyme (Lyz), respectively, was decreased by 160% and 100%. The secondary structures of 13 different proteins bound to bwGO were compared with the corresponding proteins bound to GO using the UV circular dichroism spectroscopy. There was a consistent loss of protein secondary structure with bwGO when compared with proteins bound to GO, but no correlation between either the isoelectric point or hydrophobicity of the protein and the extent of structure loss was observed. All enzymes bound to bwGO and GO indicated significant activities, and a strong correlation between the enzymatic activity and the extent of structure retention was noted, regardless of the presence or absence of OD. At low loadings (<100 μg/mL) both GO and bwGO showed excellent cell viability but substantial cytotoxicity (~40% cell death) was observed at high loadings (>100 μg/mL). In control studies, OD by itself did not alter the growth rate even after a 48-h incubation. Thus, the presence of OD in GO played a very important role in controlling the chemical and biological nature of the protein-GO interface and the presence of OD in GO improved its biological compatibility when compared to bwGO. PMID:26257893

  4. Biological effects of pramipexole on dopaminergic neuron-associated genes: relevance to neuroprotection.

    PubMed

    Pan, Tianhong; Xie, Wenjie; Jankovic, Joseph; Le, Weidong

    2005-03-29

    Pramipexole (PRX) is a non-ergot dopamine (DA) D2/D3 receptor agonist. Experimental studies have provided evidence that PRX may exert neuroprotective effects on the nigro-striatal system. Recent studies have demonstrated a slower decline of DAT density in Parkinson's disease patients treated with PRX as measured by SPECT. The aim of this study is to determine whether PRX has direct biological effects on DAergic neuron-associated genes expression, including DAT, VMAT2, and Nurr1. The human neuroblastoma SH-SY5Y cells were treated with PRX for various time periods and harvested to measure the mRNA and protein products of these genes. Treatment with PRX at 10 microM significantly increased DAT mRNA levels by 54-130% in 4-8 h, VMAT2 mRNA levels by 34% in 4 h, and Nurr1 mRNA levels by 31-39% in 2-4 h, which was the earliest induction among these three genes. The protein levels of DAT, VMAT2, and Nurr1 were markedly increased after PRX treatment, among which the increase of Nurr1 protein level was the highest at first 2 h treatment of PRX. Nafadotride, a D3 DA receptor antagonist, blocked the increase of Nurr1 gene expression induced by PRX, while eticlopride, a D2 DA receptor antagonist, didn't show this effect. Our findings that PRX has biological regulatory effects on DAergic neuron-associated genes may explain both the slower decline of imaged DAT and the neuroprotective effect of PRX. Furthermore, our results suggest that the induction of Nurr1 gene expression by PRX may be mediated by D3 DA receptor. PMID:15740846

  5. TaBoo SeArch Algorithm with a Modified Inverse Histogram for Reproducing Biologically Relevant Rare Events of Proteins.

    PubMed

    Harada, Ryuhei; Takano, Yu; Shigeta, Yasuteru

    2016-05-10

    The TaBoo SeArch (TBSA) algorithm [ Harada et al. J. Comput. Chem. 2015 , 36 , 763 - 772 and Harada et al. Chem. Phys. Lett. 2015 , 630 , 68 - 75 ] was recently proposed as an enhanced conformational sampling method for reproducing biologically relevant rare events of a given protein. In TBSA, an inverse histogram of the original distribution, mapped onto a set of reaction coordinates, is constructed from trajectories obtained by multiple short-time molecular dynamics (MD) simulations. Rarely occurring states of a given protein are statistically selected as new initial states based on the inverse histogram, and resampling is performed by restarting the MD simulations from the new initial states to promote the conformational transition. In this process, the definition of the inverse histogram, which characterizes the rarely occurring states, is crucial for the efficiency of TBSA. In this study, we propose a simple modification of the inverse histogram to further accelerate the convergence of TBSA. As demonstrations of the modified TBSA, we applied it to (a) hydrogen bonding rearrangements of Met-enkephalin, (b) large-amplitude domain motions of Glutamine-Binding Protein, and (c) folding processes of the B domain of Staphylococcus aureus Protein A. All demonstrations numerically proved that the modified TBSA reproduced these biologically relevant rare events with nanosecond-order simulation times, although a set of microsecond-order, canonical MD simulations failed to reproduce the rare events, indicating the high efficiency of the modified TBSA. PMID:27070761

  6. The autoxidation and proton dissociation constants of tertiary diphosphines: relevance to biological activity.

    PubMed

    Berners-Price, S J; Norman, R E; Sadler, P J

    1987-11-01

    The pKas and autoxidation properties of a number of diphosphines which exhibit varying degrees of antitumor and cytotoxic activity were investigated. Titration by HClO4 in CH3NO2 was used to determine pKas of the following diphosphines: R2P(CH2)nPR'2, where for R = R' = Ph, n = 1, 2, and 3 (dppm, dppe, and dppp respectively); for R = R' = Et, n = 2 (depe); for R = Ph, R' = Et, n = 2 (eppe); and for cis and trans Ph2PCH = CHPPh2 (dppey). The difference between the first and second protonation constants decreases as the length of the carbon chain between the two phosphorus centers increases. Unsaturation in the carbon chain lowers pKas. -PEt2 centers are apparently more basic than -PPh2 centers. Apart from electrostatic effects, the protonation of a given phosphine center appears to be independent of the substituents at the second phosphine center. The autoxidation reactions of dppm, dppe, dppp, depe, and cis-dppey were studied in a variety of solvents by 31P NMR spectroscopy. The ethyl-substituted diphosphines were much more rapidly oxidized than the phenyl-substituted, and the pathways of autoxidation differed. Generally, the phenyl-substituted diphosphines gave only mono- and dioxides, while the ethyl-substituted diphosphines additionally gave phosphinites and other oxidation products. The relevance of the autoxidation reactivity and the pKas to the contrasting antitumor activity of these diphosphines is discussed. PMID:2828542

  7. Biological Production of a Hydrocarbon Fuel Intermediate Polyhydroxybutyrate (Phb) from a Process Relevant Lignocellulosic Derived Sugar

    SciTech Connect

    Wang, Wei; Mohagheghi, Ali; Mittal, Ashutosh; Pilath, Heidi; Johnson, David K.

    2015-03-22

    PHAs are synthesized by many microorganisms to serve as intracellular carbon storage molecules. In some bacterial strains, PHB can account for up to 80% of cell mass. In addition to its application in the packaging sector, PHB also has great potential as an intermediate in the production of hydrocarbon fuels. PHB can be thermally depolymerized and decarboxylated to propene which can be upgraded to hydrocarbon fuels via commercial oligomerization technologies. In recent years a great effort has been made in bacterial production of PHB, yet the production cost of the polymer is still much higher than conventional petrochemical plastics. The high cost of PHB is because the cost of the substrates can account for as much as half of the total product cost in large scale fermentation. Thus searching for cheaper and better substrates is very necessary for PHB production. In this study, we demonstrate production of PHB by Cupriavidus necator from a process relevant lignocellulosic derived sugar stream, i.e., saccharified hydrolysate slurry from pretreated corn stover. Good cell growth was observed on slurry saccharified with advanced enzymes and 40~60% of PHB was accumulated in the cells. The mechanism of inhibition in the toxic hydrolysate generated by pretreatment and saccharification of biomass, will be discussed.

  8. Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies.

    PubMed

    Shaver, Timothy M; Lehmann, Brian D; Beeler, J Scott; Li, Chung-I; Li, Zhu; Jin, Hailing; Stricker, Thomas P; Shyr, Yu; Pietenpol, Jennifer A

    2016-08-15

    Triple-negative breast cancer (TNBC) and other molecularly heterogeneous malignancies present a significant clinical challenge due to a lack of high-frequency "driver" alterations amenable to therapeutic intervention. These cancers often exhibit genomic instability, resulting in chromosomal rearrangements that affect the structure and expression of protein-coding genes. However, identification of these rearrangements remains technically challenging. Using a newly developed approach that quantitatively predicts gene rearrangements in tumor-derived genetic material, we identified and characterized a novel oncogenic fusion involving the MER proto-oncogene tyrosine kinase (MERTK) and discovered a clinical occurrence and cell line model of the targetable FGFR3-TACC3 fusion in TNBC. Expanding our analysis to other malignancies, we identified a diverse array of novel and known hybrid transcripts, including rearrangements between noncoding regions and clinically relevant genes such as ALK, CSF1R, and CD274/PD-L1 The over 1,000 genetic alterations we identified highlight the importance of considering noncoding gene rearrangement partners, and the targetable gene fusions identified in TNBC demonstrate the need to advance gene fusion detection for molecularly heterogeneous cancers. Cancer Res; 76(16); 4850-60. ©2016 AACR. PMID:27231203

  9. O2 reduction reaction by biologically relevant anionic ligand bound iron porphyrin complexes.

    PubMed

    Samanta, Subhra; Das, Pradip Kumar; Chatterjee, Sudipta; Sengupta, Kushal; Mondal, Biswajit; Dey, Abhishek

    2013-11-18

    Iron porphyrin complex with a covalently attached thiolate ligand and another with a covalently attached phenolate ligand has been synthesized. The thiolate bound complex shows spectroscopic features characteristic of P450, including the hallmark absorption spectrum of the CO adduct. Electrocatalytic O2 reduction by this complex, which bears a terminal alkyne group, is investigated by both physiabsorbing on graphite surfaces (fast electron transfer rates) and covalent attachment to azide terminated self-assembled monolayer (physiologically relevant electron transfer rates) using the terminal alkyne group. Analysis of the steady state electrochemical kinetics reveals that this catalyst can selectively reduce O2 to H2O with a second-order k(cat.) ~10(7) M(-1 )s(-1) at pH 7. The analogous phenolate bound iron porphyrin complex reduces O2 with a second-order rate constant of 10(5) M(-1) s(-1) under the same conditions. The anionic ligand bound iron porphyrin complexes catalyze oxygen reduction reactions faster than any known synthetic heme porphyrin analogues. The kinetic parameters of O2 reduction of the synthetic thiolate bound complex, which is devoid of any second sphere effects present in protein active sites, provide fundamental insight into the role of the protein environment in tuning the reactivity of thiolate bound iron porphyrin containing metalloenzymes. PMID:24171513

  10. Reactions of HNO with metal porphyrins: underscoring the biological relevance of HNO.

    PubMed

    Doctorovich, Fabio; Bikiel, Damian E; Pellegrino, Juan; Suárez, Sebastián A; Martí, Marcelo A

    2014-10-21

    Azanone ((1)HNO, nitroxyl) shows interesting yet poorly understood chemical and biological effects. HNO has some overlapping properties with nitric oxide (NO), sharing its biological reactivity toward heme proteins, thiols, and oxygen. Despite this similarity, HNO and NO show significantly different pharmacological effects. The high reactivity of HNO means that studies must rely on the use of donor molecules such as trioxodinitrate (Angeli's salt). It has been suggested that azanone could be an intermediate in several reactions and that it may be an enzymatically produced signaling molecule. The inherent difficulty in detecting its presence unequivocally prevents evidence from yielding definite answers. On the other hand, metalloporphyrins are widely used as chemical models of heme proteins, providing us with invaluable tools for the study of the coordination chemistry of small molecules, like NO, CO, and O2. Studies with transition metal porphyrins have shown diverse mechanistic, kinetic, structural, and reactive aspects related to the formation of nitrosyl complexes. Porphyrins are also widely used in technical applications, especially when coupled to a surface, where they can be used as electrochemical gas sensors. Given their versatility, they have not escaped their role as key players in chemical studies involving HNO. This Account presents the research performed during the last 10 years in our group concerning azanone reactions with iron, manganese, and cobalt porphyrins. We begin by describing their HNO trapping capabilities, which result in formation of the corresponding nitrosyl complexes. Kinetic and mechanistic studies of these reactions show two alternative operating mechanisms: reaction of the metal center with HNO or with the donor. Moreover, we have also shown that azanone can be stabilized by coordination to iron porphyrins using electron-attracting substituents attached to the porphyrin ring, which balance the negatively charged NO¯. Second, we

  11. Biological, Clinical, and Population Relevance of 95 Loci for Blood Lipids

    PubMed Central

    Teslovich, Tanya M.; Musunuru, Kiran; Smith, Albert V.; Edmondson, Andrew C.; Stylianou, Ioannis M.; Koseki, Masahiro; Pirruccello, James P.; Ripatti, Samuli; Chasman, Daniel I.; Willer, Cristen J.; Johansen, Christopher T.; Fouchier, Sigrid W.; Isaacs, Aaron; Peloso, Gina M.; Barbalic, Maja; Ricketts, Sally L.; Bis, Joshua C.; Aulchenko, Yurii S.; Thorleifsson, Gudmar; Feitosa, Mary F.; Chambers, John; Orho-Melander, Marju; Melander, Olle; Johnson, Toby; Li, Xiaohui; Guo, Xiuqing; Li, Mingyao; Cho, Yoon Shin; Go, Min Jin; Kim, Young Jin; Lee, Jong-Young; Park, Taesung; Kim, Kyunga; Sim, Xueling; Ong, Rick Twee-Hee; Croteau-Chonka, Damien C.; Lange, Leslie A.; Smith, Joshua D.; Song, Kijoung; Zhao, Jing Hua; Yuan, Xin; Luan, Jian'an; Lamina, Claudia; Ziegler, Andreas; Zhang, Weihua; Zee, Robert Y.L.; Wright, Alan F.; Witteman, Jacqueline C.M.; Wilson, James F.; Willemsen, Gonneke; Wichmann, H-Erich; Whitfield, John B.; Waterworth, Dawn M.; Wareham, Nicholas J.; Waeber, Gérard; Vollenweider, Peter; Voight, Benjamin F.; Vitart, Veronique; Uitterlinden, Andre G.; Uda, Manuela; Tuomilehto, Jaakko; Thompson, John R.; Tanaka, Toshiko; Surakka, Ida; Stringham, Heather M.; Spector, Tim D.; Soranzo, Nicole; Smit, Johannes H.; Sinisalo, Juha; Silander, Kaisa; Sijbrands, Eric J.G.; Scuteri, Angelo; Scott, James; Schlessinger, David; Sanna, Serena; Salomaa, Veikko; Saharinen, Juha; Sabatti, Chiara; Ruokonen, Aimo; Rudan, Igor; Rose, Lynda M.; Roberts, Robert; Rieder, Mark; Psaty, Bruce M.; Pramstaller, Peter P.; Pichler, Irene; Perola, Markus; Penninx, Brenda W.J.H.; Pedersen, Nancy L.; Pattaro, Cristian; Parker, Alex N.; Pare, Guillaume; Oostra, Ben A.; O'Donnell, Christopher J.; Nieminen, Markku S.; Nickerson, Deborah A.; Montgomery, Grant W.; Meitinger, Thomas; McPherson, Ruth; McCarthy, Mark I.; McArdle, Wendy; Masson, David; Martin, Nicholas G.; Marroni, Fabio; Mangino, Massimo; Magnusson, Patrik K.E.; Lucas, Gavin; Luben, Robert; Loos, Ruth J. F.; Lokki, Maisa; Lettre, Guillaume; Langenberg, Claudia; Launer, Lenore J.; Lakatta, Edward G.; Laaksonen, Reijo; Kyvik, Kirsten O.; Kronenberg, Florian; König, Inke R.; Khaw, Kay-Tee; Kaprio, Jaakko; Kaplan, Lee M.; Johansson, Åsa; Jarvelin, Marjo-Riitta; Janssens, A. Cecile J.W.; Ingelsson, Erik; Igl, Wilmar; Hovingh, G. Kees; Hottenga, Jouke-Jan; Hofman, Albert; Hicks, Andrew A.; Hengstenberg, Christian; Heid, Iris M.; Hayward, Caroline; Havulinna, Aki S.; Hastie, Nicholas D.; Harris, Tamara B.; Haritunians, Talin; Hall, Alistair S.; Gyllensten, Ulf; Guiducci, Candace; Groop, Leif C.; Gonzalez, Elena; Gieger, Christian; Freimer, Nelson B.; Ferrucci, Luigi; Erdmann, Jeanette; Elliott, Paul; Ejebe, Kenechi G.; Döring, Angela; Dominiczak, Anna F.; Demissie, Serkalem; Deloukas, Panagiotis; de Geus, Eco J.C.; de Faire, Ulf; Crawford, Gabriel; Collins, Francis S.; Chen, Yii-der I.; Caulfield, Mark J.; Campbell, Harry; Burtt, Noel P.; Bonnycastle, Lori L.; Boomsma, Dorret I.; Boekholdt, S. Matthijs; Bergman, Richard N.; Barroso, Inês; Bandinelli, Stefania; Ballantyne, Christie M.; Assimes, Themistocles L.; Quertermous, Thomas; Altshuler, David; Seielstad, Mark; Wong, Tien Y.; Tai, E-Shyong; Feranil, Alan B.; Kuzawa, Christopher W.; Adair, Linda S.; Taylor, Herman A.; Borecki, Ingrid B.; Gabriel, Stacey B.; Wilson, James G.; Stefansson, Kari; Thorsteinsdottir, Unnur; Gudnason, Vilmundur; Krauss, Ronald M.; Mohlke, Karen L.; Ordovas, Jose M.; Munroe, Patricia B.; Kooner, Jaspal S.; Tall, Alan R.; Hegele, Robert A.; Kastelein, John J.P.; Schadt, Eric E.; Rotter, Jerome I.; Boerwinkle, Eric; Strachan, David P.; Mooser, Vincent; Holm, Hilma; Reilly, Muredach P.; Samani, Nilesh J; Schunkert, Heribert; Cupples, L. Adrienne; Sandhu, Manjinder S.; Ridker, Paul M; Rader, Daniel J.; van Duijn, Cornelia M.; Peltonen, Leena; Abecasis, Gonçalo R.; Boehnke, Michael; Kathiresan, Sekar

    2010-01-01

    Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with serum lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 × 10-8), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (e.g., CYP7A1, NPC1L1, and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and impact lipid traits in three non-European populations (East Asians, South Asians, and African Americans). Our results identify several novel loci associated with serum lipids that are also associated with CAD. Finally, we validated three of the novel genes—GALNT2, PPP1R3B, and TTC39B—with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD. PMID:20686565

  12. Altitude training causes haematological fluctuations with relevance for the Athlete Biological Passport.

    PubMed

    Bonne, Thomas Christian; Lundby, Carsten; Lundby, Anne Kristine; Sander, Mikael; Bejder, Jacob; Nordsborg, Nikolai Baastrup

    2015-08-01

    The impact of altitude training on haematological parameters and the Athlete Biological Passport (ABP) was evaluated in international-level elite athletes. One group of swimmers lived high and trained high (LHTH, n = 10) for three to four weeks at 2130 m or higher whereas a control group (n = 10) completed a three-week training camp at sea-level. Haematological parameters were determined weekly three times before and four times after the training camps. ABP thresholds for haemoglobin concentration ([Hb]), reticulocyte percentage (RET%), OFF score and the abnormal blood profile score (ABPS) were calculated using the Bayesian model. After altitude training, six swimmers exceeded the 99% ABP thresholds: two swimmers exceeded the OFF score thresholds at day +7; one swimmer exceeded the OFF score threshold at day +28; one swimmer exceeded the threshold for RET% at day +14; and one swimmer surpassed the ABPS threshold at day +14. In the control group, no values exceeded the individual ABP reference range. In conclusion, LHTH induces haematological changes in Olympic-level elite athletes which can exceed the individually generated references in the ABP. Training at altitude should be considered a confounding factor for ABP interpretation for up to four weeks after altitude exposure but does not consistently cause abnormal values in the ABP. PMID:25545030

  13. Photochemical reactions of metal nitrosyl complexes. Mechanisms of NO reactions with biologically relevant metal centers

    DOE PAGESBeta

    Ford, Peter C.

    2001-01-01

    Tmore » he discoveries that nitric oxide (a.k.a. nitrogen monoxide) serves important roles in mammalian bioregulation and immunology have stimulated intense interest in the chemistry and biochemistry of NO and derivatives such as metal nitrosyl complexes. Also of interest are strategies to deliver NO to biological targets on demand. One such strategy would be to employ a precursor which displays relatively low thermal reactivity but is photochemically active to release NO.his proposition led us to investigate laser flash and continuous photolysis kinetics of nitrosyl complexes such as the Roussin's iron-sulfur-nitrosyl cluster anions Fe 2 S 2 ( NO ) 4 2 − and Fe 4 S 3 ( NO ) 7 − and several ruthenium salen and porphyrin nitrosyls.hese include studies using metal-nitrosyl photochemistry as a vehicle for delivering NO to hypoxic cell cultures in order to sensitize γ -radiation damage. Also studied were the rates and mechanisms of NO “on” reactions with model water soluble heme compounds, the ferriheme protein met-myoglobin and various ruthenium complexes using ns laser flash photolysis techniques. An overview of these studies is presented.« less

  14. Next generation techniques in the high resolution spectroscopy of biologically relevant molecules.

    PubMed

    Neill, Justin L; Douglass, Kevin O; Pate, Brooks H; Pratt, David W

    2011-04-28

    Recent advances in the technology of test and measurement equipment driven by the computer and telecommunications industries have made possible the development of a new broadband, Fourier-transform microwave spectrometer that operates on principles similar to FTNMR. This technique uses a high sample-rate arbitrary waveform generator to construct a phase-locked chirped microwave pulse that gives a linear frequency sweep over a wide frequency range in 1 μs. The chirped pulse efficiently polarizes the molecular sample at all frequencies lying within this band. The subsequent free induction decay of this polarization is measured with a high-speed digitizer and then fast Fourier-transformed to yield a broadband, frequency-resolved rotational spectrum, spanning up to 11.5 GHz and containing lines that are as narrow as 100 kHz. This new technique is called chirped-pulse Fourier transform microwave (CP-FTMW) spectroscopy. The technique offers the potential to determine the structural and dynamical properties of very large molecules solely from fully resolved pure rotational spectra. FTMW double resonance techniques employing a low-resolution UV laser facilitate an easy assignment of overlapping spectra produced by different conformers in the sample. Of particular interest are the energy landscapes of conformationally flexible molecules of biological importance, including studies of their interaction with solvent and/or other weakly bound molecules. An example is provided from the authors' work on p-methoxyphenethylamine, a neurotransmitter, and its complexes with water. PMID:21394332

  15. Food Polyphenols Fail to Cause a Biologically Relevant Reduction of COX-2 Activity

    PubMed Central

    Willenberg, Ina; Meschede, Anna K.; Gueler, Faikah; Jang, Mi-Sun; Shushakova, Nelli; Schebb, Nils Helge

    2015-01-01

    Epidemiologic studies show a correlation between the dietary intake of food polyphenols and beneficial health effects. Several in vitro studies indicate that the anti-inflammatory potential of polyphenols is, at least in part, mediated by a modulation of the enzymes of the arachidonic acid cascade, such as the prostaglandin forming cyclooxygenases (COXs). Evidence that this mode of action can be transferred to the situation in vivo is scarce. This study characterized effects of a subset of polyphenols on COX–2 expression and activity in vitro and compared the potency with known drugs. Next, the in vivo relevance of the observed in vitro effects was tested. Enzyme assays and incubations of polyphenols with the cancer cell line HCA–7 and lipopolysaccharide (LPS) stimulated primary monocytes support the hypothesis that polyphenols can effect COX–2 expression and activity in vitro. The effects were most pronounced in the monocyte assay for wogonin, apigenin, resveratrol and genistein with IC50 values of 1.5 μM, 2.6 μM, 2.8 μM and 7.4 μM. However, these values are 100- to 1000-fold higher in comparison to those of the known pharmaceuticals celecoxib, indomethacin and dexamethasone. In an animal model of LPS induced sepsis, pretreatment with polyphenols (i. p. 100 mg/kg bw) did not result in decreased plasma or tissue prostaglandin levels, whereas the positive control celecoxib effectively attenuated LPS induced prostaglandin formation. These data suggest that despite the moderate potency in vitro, an effect of polyphenols on COX–2 during acute inflammation is unlikely, even if a high dose of polyphenols is ingested. PMID:26440517

  16. Prognostic value and in vitro biological relevance of Neuropilin 1 and Neuropilin 2 in osteosarcoma.

    PubMed

    Boro, Aleksandar; Arlt, Matthias Je; Lengnick, Harald; Robl, Bernhard; Husmann, Maren; Bertz, Josefine; Born, Walter; Fuchs, Bruno

    2015-01-01

    Neoadjuvant chemotherapy in osteosarcoma increased the long-term survival of patients with localized disease considerably but metastasizing osteosarcoma remained largely treatment resistant. Neuropilins, transmembrane glycoproteins, are important receptors for VEGF dependent hyper-vascularization in tumor angiogenesis and their aberrant expression promotes tumorigenesis and metastasis in many solid tumors. Our analysis of Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2) immunostaining in a tissue microarray of 66 osteosarcoma patients identified NRP2 as an indicator of poor overall, metastasis-free and progression free survival while NRP1 had no predictive value. Patients with tumors that expressed NRP2 in the absence of NRP1 had a significantly worse prognosis than NRP1(-)/NRP2(-), NRP1(+) or NRP1(+)/NRP2(+) tumors. Moreover, patients with overt metastases and with NRP2-positive primary tumors had a significantly shorter survival rate than patients with metastases but NRP2-negative tumors. Furthermore, the expression of both NRP1 and NRP2 in osteosarcoma cell lines correlated to a variable degree with the metastatic potential of the respective cell line. To address the functional relevance of Neuropilins for VEGF signaling we used shRNA mediated down-regulation and blocking antibodies of NRP1 and NRP2 in the metastatic 143B and HuO9-M132 cell lines. In 143B cells, VEGFA signaling monitored by AKT phosphorylation was more inhibited by blocking of NRP1, whereas in HuO9-M132 cells NRP2 blocking was more effective indicating that NRP1 and NRP2 can substitute each other in the functional interaction with VEGFR1. Altogether, these data point to NRP2 as a powerful prognostic marker in osteosarcoma and together with NRP1 as a novel target for tumor-suppressive therapy. PMID:26045903

  17. C-MAF oncogene dysregulation in multiple myeloma: frequency and biological relevance.

    PubMed

    Rasmussen, Thomas; Knudsen, Lene Meldgaard; Dahl, Inger Marie S; Johnsen, Hans Erik

    2003-10-01

    To investigate the frequency and possible biological consequences of c-maf dysregulation, we designed c-maf and IL-4 real-time RT-PCR assays for determination of c-maf and IL-4 mRNA levels. Using the c-maf real-time RT-PCR assay, we tested a panel of 14 B-cell lines, 135 diagnostic bone marrow (BM) samples from patients with multiple myeloma and 10 BM samples from normal donors. In B cell lines and flowsorted CD38++/CD19-/CD56++ myeloma plasma cells (N = 14) the c-maf/GAPDH and IL-4/GAPDH ratios were determined simultaneously using real time RT-PCR. All B cell lines used in the study were characterized by flow cytometry and tested for the presence of Ebstein-Barr virus (EBV). B-cell lines, that were PCR negative for EBV and had a phenotype typical for primary myeloma cells, expressed medium to high levels of c-maf mRNA. However, all EBV PCR positive cell lines, showed a more immature phenotype, lacked expression of aberrant surface markers and contained very low levels of c-maf mRNA. In 4.4% (6/135) of MM patients tested, a c-maf mRNA level comparable to the cell line RPMI 8226 containing at (16:22), translocation was found. In addition, all c-maf positive myeloma cell lines and CD38++/CD19-/CD56++ myeloma plasma cells tested were IL-4 negative. In conclusion, high levels of c-maf mRNA were observed in "true MM cell lines" and 4.4% of MM patients. Further, c-maf dysregulation in myeloma plasma cells did not cause induction of IL-4 transcription. PMID:14692531

  18. Biological processes and optical measurements near the sea surface: Some issues relevant to remote sensing

    NASA Technical Reports Server (NTRS)

    Cullen, John J.; Lewis, Marlon R.

    1995-01-01

    The advent of remote sensing, the develpmemt of new optical instrumentation, and the associated advances in hydrological optics have transformed oceanography; it is now feasible to describe ocean-scale biogeochemical dynamcis from satellite observations, verified and complemented by measurements from optical sensors on profilers, moorings, and drifters. Only near-surface observations are common to both remote sensing and in situ observation, so it is critical to understand processes in the upper euphotic zone. Unfortunately, the biological principles that must be used to interpret optical variability near the sea surface are weaker than we would like, because relatively few experiments and analyses have examined bio-optical relationships under high irradiance characteristic of the upper optical depth. Special consideration of this stratum is justified, because there is good evidence that bio-optical relationships are altered near the surface; (1) the fluorescence yield from chlorophyll declines, leading to bias in the estimation of pigment from fluorometry; (2) the modeled relationship between solar-stimulated fluorecence and photosynthesis seems to deviate significantly from that presented for the lower euphotic zone; and (3) carbon-specific and cellular attenuation cross sections of phytoplankton change substantially during exposures to bright light. Even the measurement of primary productivity is problematic near the sea surface, because vertical mixing is not simulated and artifactual inhibition of photosynthesis can result. These problems can be addressed by focusing more sampling effort, experimental simulation, and analytical consideration on the upper optical depth, and by shortening timescales for the measurement of marine photosynthesis. Special efforts to study near-surface processes are justified, because new bio-optical algorithms will require quantitaitve descriptions of the responses of phytoplankton to bright light.

  19. Developing mononuclear copper-active-oxygen complexes relevant to reactive intermediates of biological oxidation reactions.

    PubMed

    Itoh, Shinobu

    2015-07-21

    Active-oxygen species generated on a copper complex play vital roles in several biological and chemical oxidation reactions. Recent attention has been focused on the reactive intermediates generated at the mononuclear copper active sites of copper monooxygenases such as dopamine β-monooxygenase (DβM), tyramine β-monooxygenase (TβM), peptidylglycine-α-hydroxylating monooxygenase (PHM), and polysaccharide monooxygenases (PMO). In a simple model system, reaction of O2 and a reduced copper(I) complex affords a mononuclear copper(II)-superoxide complex or a copper(III)-peroxide complex, and subsequent H(•) or e(-)/H(+) transfer, which gives a copper(II)-hydroperoxide complex. A more reactive species such as a copper(II)-oxyl radical type species could be generated via O-O bond cleavage of the peroxide complex. However, little had been explored about the chemical properties and reactivity of the mononuclear copper-active-oxygen complexes due to the lack of appropriate model compounds. Thus, a great deal of effort has recently been made to develop efficient ligands that can stabilize such reactive active-oxygen complexes in synthetic modeling studies. In this Account, I describe our recent achievements of the development of a mononuclear copper(II)-(end-on)superoxide complex using a simple tridentate ligand consisting of an eight-membered cyclic diamine with a pyridylethyl donor group. The superoxide complex exhibits a similar structure (four-coordinate tetrahedral geometry) and reactivity (aliphatic hydroxylation) to those of a proposed reactive intermediate of copper monooxygenases. Systematic studies based on the crystal structures of copper(I) and copper(II) complexes of the related tridentate supporting ligands have indicated that the rigid eight-membered cyclic diamine framework is crucial for controlling the geometry and the redox potential, which are prerequisites for the generation of such a unique mononuclear copper(II)-(end-on)superoxide complex

  20. Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms

    PubMed Central

    Ogata, Toru; Shibamura, Hidenori; Tromp, Gerard; Sinha, Moumita; Goddard, Katrina A. B.; Sakalihasan, Natzi; Limet, Raymond; MacKean, Gerald L.; Arthur, Claudette; Sueda, Taijiro; Land, Susan; Kuivaniemi, Helena

    2005-01-01

    findings suggest that genetic variations in TIMP1, TIMP3, MMP10, and ELN genes may contribute to the pathogenesis of AAAs. Further work is needed to confirm the findings in an independent set of samples and to study the functional role of these variants in AAA. It is noteworthy that contrary to a previous study, we did not find an association between the MMP9 (nt−1562) polymorphism and AAA, suggesting genetic heterogeneity of the disease. Clinical Relevance Abdominal aortic aneurysms (AAAs) are an important cardiovascular disease, but the genetic and environmental risk factors, which contribute to individual’s risk to develop an aneurysm, are poorly understood. Histologically, AAAs are characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. We hypothesized that genes involved in these events could harbor changes that make individuals more susceptible to developing aneurysms. This study identified significant genetic associations between DNA sequence changes in tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and elastin (ELN) genes, and AAA. The results will require confirmation using an independent set of samples. After replication it is possible that these sequence changes in combination with other risk factors could be used in the future to identify individuals who are at increased risk for developing an AAA. PMID:15944607

  1. The scaling law of climate change and its relevance to assessing (palaeo)biological responses

    NASA Astrophysics Data System (ADS)

    Kiessling, Wolfgang; Eichenseer, Kilian

    2014-05-01

    interglacials, are not monotonic, but punctuated by short-term cooling intervals. The fossil record tells us that biodiversity responded dramatically to ancient intervals of climate warming. We can now see that the apparently slower rates of change in some mass extinctions (Permian-Triassic, Triassic-Jurassic) were greater than today when the scaling law is considered. This reassures us that studying deep time patterns of organismic response to climate change is a worthwhile endeavor that is relevant for predicting the future. References Burrows, M. T., Schoeman, D. S., Buckley, L. B., Moore, P., Poloczanska, E. S., Brander, K. M., Brown, C., Bruno, J. F., Duarte, C. M., Halpern, B. S., Holding, J., Kappel, C. V., Kiessling, W., O'Connor, M. I., Pandolfi, J. M., Parmesan, C., Schwing, F. B., Sydeman, W. J., and Richardson, A. J.: The pace of shifting climate in marine and terrestrial ecosystems, Science, 334, 652-655, 2011. Gingerich, P. D.: Quantification and comparison of evolutionary rates, American Journal of Science, 293A, 453-478, 1993. Sadler, P. M.: Sediment accumulation rates and the completeness of stratigraphic sections, Journal of Geology, 89, 569-584, 1981. Sun, Y., Joachimski, M. M., Wignall, P. B., Yan, C., Chen, Y., Jiang, H., Wang, L., and Lai, X.: Lethally hot temperatures during the Early Triassic greenhouse, Science, 338, 366-370, 2012.

  2. Culturally Relevant Inquiry-Based Laboratory Module Implementations in Upper-Division Genetics and Cell Biology Teaching Laboratories

    PubMed Central

    Siritunga, Dimuth; Montero-Rojas, María; Carrero, Katherine; Toro, Gladys; Vélez, Ana; Carrero-Martínez, Franklin A.

    2011-01-01

    Today, more minority students are entering undergraduate programs than ever before, but they earn only 6% of all science or engineering PhDs awarded in the United States. Many studies suggest that hands-on research activities enhance students’ interest in pursuing a research career. In this paper, we present a model for the implementation of laboratory research in the undergraduate teaching laboratory using a culturally relevant approach to engage students. Laboratory modules were implemented in upper-division genetics and cell biology courses using cassava as the central theme. Students were asked to bring cassava samples from their respective towns, which allowed them to compare their field-collected samples against known lineages from agricultural stations at the end of the implementation. Assessment of content and learning perceptions revealed that our novel approach allowed students to learn while engaged in characterizing Puerto Rican cassava. In two semesters, based on the percentage of students who answered correctly in the premodule assessment for content knowledge, there was an overall improvement of 66% and 55% at the end in the genetics course and 24% and 15% in the cell biology course. Our proposed pedagogical model enhances students’ professional competitiveness by providing students with valuable research skills as they work on a problem to which they can relate. PMID:21885825

  3. The practicalities and pitfalls of establishing a policy-relevant and cost-effective soil biological monitoring scheme.

    PubMed

    Faber, Jack H; Creamer, Rachel E; Mulder, Christian; Römbke, Jörg; Rutgers, Michiel; Sousa, J Paulo; Stone, Dorothy; Griffiths, Bryan S

    2013-04-01

    A large number of biological indicators have been proposed over the years for assessing soil quality. Although many of those have been applied in monitoring schemes across Europe, no consensus exists on the extent to which these indicators might perform best and how monitoring schemes can be further optimized in terms of scientific and policy relevance. Over the past decade, developments in environmental monitoring and risk assessment converged toward the use of indicators and endpoints that are related to soil functioning and ecosystem services. In view of the proposed European Union (EU) Soil Framework Directive, there is an urgent need to identify and evaluate indicators for soil biodiversity and ecosystem services. The recently started integrated project, Ecological Function and Biodiversity Indicators in European Soils (EcoFINDERS), aims to address this specific issue within the EU Framework Program FP7. Here, we 1) discuss how to use the concept of ecosystem services in soil monitoring, 2) review former and ongoing monitoring schemes, and 3) present an analysis of metadata on biological indicators in some EU member states. Finally, we discuss our experiences in establishing a logical sieve approach to devise a monitoring scheme for a standardized and harmonized application at European scale. PMID:23325463

  4. Spatial release from masking improves sound pattern discrimination along a biologically relevant pulse-rate continuum in gray treefrogs

    PubMed Central

    Ward, Jessica L.; Buerkle, Nathan P.; Bee, Mark A.

    2013-01-01

    Frogs form large choruses during the mating season in which males produce loud advertisement calls to attract females and repel rival males. High background noise levels in these social aggregations can impair vocal perception. In humans, spatial release from masking contributes to our ability to understand speech in noisy social groups. Here, we tested the hypothesis that spatial separation between target signals and ‘chorus-shaped noise’ improves the ability of female gray treefrogs (Hyla chrysoscelis) to perform a behavioral discrimination task based on perceiving differences in the pulsatile structure of advertisement calls. We used two-stimulus choice tests to measure phonotaxis (approach toward sound) in response to calls differing in pulse rate along a biologically relevant continuum between conspecific (50 pulses s−1) and heterospecific (20 pulses s−1) calls. Signals were presented in quiet, in colocated noise, and in spatially separated noise. In quiet conditions, females exhibited robust preferences for calls with relatively faster pulse rates more typical of conspecific calls. Behavioral discrimination between calls differing in pulse rate was impaired in the presence of colocated noise but similar between quiet and spatially separated noise conditions. Our results indicate that spatial release from energetic masking facilitates a biologically important temporal discrimination task in frogs. We discuss these results in light of previous work on spatial release from masking in frogs and other animals. PMID:24055623

  5. Culturally relevant inquiry-based laboratory module implementations in upper-division genetics and cell biology teaching laboratories.

    PubMed

    Siritunga, Dimuth; Montero-Rojas, María; Carrero, Katherine; Toro, Gladys; Vélez, Ana; Carrero-Martínez, Franklin A

    2011-01-01

    Today, more minority students are entering undergraduate programs than ever before, but they earn only 6% of all science or engineering PhDs awarded in the United States. Many studies suggest that hands-on research activities enhance students' interest in pursuing a research career. In this paper, we present a model for the implementation of laboratory research in the undergraduate teaching laboratory using a culturally relevant approach to engage students. Laboratory modules were implemented in upper-division genetics and cell biology courses using cassava as the central theme. Students were asked to bring cassava samples from their respective towns, which allowed them to compare their field-collected samples against known lineages from agricultural stations at the end of the implementation. Assessment of content and learning perceptions revealed that our novel approach allowed students to learn while engaged in characterizing Puerto Rican cassava. In two semesters, based on the percentage of students who answered correctly in the premodule assessment for content knowledge, there was an overall improvement of 66% and 55% at the end in the genetics course and 24% and 15% in the cell biology course. Our proposed pedagogical model enhances students' professional competitiveness by providing students with valuable research skills as they work on a problem to which they can relate. PMID:21885825

  6. Quantum Dots: An Insight and Perspective of Their Biological Interaction and How This Relates to Their Relevance for Clinical Use

    PubMed Central

    Clift, Martin J. D.; Stone, Vicki

    2012-01-01

    Due to their novel physico-chemical characteristics, semi-conductor nanocrystal quantum dots (QDs) provide an advantageous perspective towards numerous different consumer and medical applications. The most notable potential application of QDs is their use as therapeutic and diagnostic tools in nanomedicine. Despite the many benefits posed by QDs, the proposed, intentional exposure to humans has raised concerns towards their potential impact upon human health. These concerns are predominantly based upon the heterogeneous composition of QDs, which most commonly comprises of a cadmium-based core and zinc sulphide shell. Whilst other nanoparticle (NP) types possess a similar structure to QDs (i.e. core-shell technology (e.g. Fe2O3, Au and superparamagnetic iron oxide NPs)), the importance of the concerns surrounding human exposure to QDs is amplified further since, due to the sophisticated chemical and light-emitting properties of QDs, the use of these NPs within any (nano)medical setting/application could be suggested as realistic, rather than simply an advantageous possibility. It is therefore imperative that a thorough understanding of how QDs interact with various biological systems, predominantly those relative to humans and what the consequences of such interactions are is gained with extreme alacrity. It is the aim of this review to highlight the current knowledge base of QD-biological system interactions, where the knowledge gaps (still) remain and how the understanding of this interaction relates to the most notable of applications for QDs; their clinical relevance. PMID:22896769

  7. Biologically relevant 3D tumor arrays: imaging-based methods for quantification of reproducible growth and analysis of treatment response

    NASA Astrophysics Data System (ADS)

    Celli, Jonathan P.; Rizvi, Imran; Blanden, Adam R.; Abu-Yousif, Adnan O.; Spring, Bryan Q.; Hasan, Tayyaba

    2011-02-01

    Three-dimensional in vitro tumor models have emerged as powerful research tools in cancer biology, though the vast potential of these systems as high-throughput, biologically relevant reporters of treatment response has yet to be adequately explored. Here, building on previous studies, we demonstrate the utility of using 3D models for ovarian and pancreatic cancers in conjunction with quantitative image processing to reveal aspects of growth behavior and treatment response that would not be evident without either modeling or quantitative analysis component. In this report we specifically focus on recent improvements in the imaging component of this integrative research platform and emphasize analysis to establish reproducible growth properties in 3D tumor arrays, a key consideration in establishing the utility of this platform as a reliable reporter of therapeutic response. Building on previous studies using automated segmentation of low magnification image fields containing large numbers of nodules to study size dependent treatment effects, we introduce an improvement to this method using multiresolution decomposition to remove gradient background from transmitted light images for more reliable feature identification. This approach facilitates the development of a new treatment response metric, disruption fraction (Dfrac), which quantifies dose dependent distribution shifts from nodular fragmentation induced by cytotoxic therapies. Using this approach we show that PDT treatment is associated with significant dose-dependent increases in Dfrac, while this is not observed with carboplatin treatment. The ability to quantify this response to therapy could play a key role in design of combination regimens involving these two modalities.

  8. Sex differences in panic-relevant responding to a 10% carbon dioxide-enriched air biological challenge.

    PubMed

    Nillni, Yael I; Berenz, Erin C; Rohan, Kelly J; Zvolensky, Michael J

    2012-01-01

    The current study examined sex differences in psychological (i.e., self-reported anxiety, panic symptoms, and avoidance) and physiological (i.e., heart rate and skin conductance level) response to, and recovery from, a laboratory biological challenge. Participants were a community-recruited sample of 128 adults (63.3% women; M(age)=23.2 years, SD=8.9) who underwent a 4-min 10% CO(2)-enriched air biological challenge. As predicted, women reported more severe physical panic symptoms and avoidance (i.e., less willingness to participate in another challenge) and demonstrated increased heart rate as compared to men above and beyond the variance accounted for by other theoretically relevant variables (recent panic attack history, neuroticism, and anxiety sensitivity). Additionally, women demonstrated a faster rate of recovery with respect to heart rate compared to men. These results are in line with literature documenting sex-specific differences in panic psychopathology, and results are discussed in the context of possible mechanisms underlying sex differences in panic vulnerability. PMID:22115836

  9. The development of Army relevant peptide-based surface enhanced Raman scattering (SERS) sensors for biological threat detection

    NASA Astrophysics Data System (ADS)

    Farrell, Mikella E.; Strobbia, Pietro; Sarkes, Deborah A.; Stratis-Cullum, Dimitra N.; Cullum, Brian M.; Pellegrino, Paul M.

    2016-05-01

    The utility of peptide-based molecular sensing for the development of novel biosensors has resulted in a significant increase in their development and usage for sensing targets like chemical, biological, energetic and toxic materials. Using peptides as a molecular recognition element is particularly advantageous because there are several mature peptide synthesis protocols that already exist, peptide structures can be tailored, selected and manipulated to be highly discerning towards desired targets, peptides can be modified to be very stable in a host of environments and stable under many different conditions, and through the development of bifunctionalized peptides can be synthesized to also bind onto desired sensing platforms (various metal materials, glass, etc.). Two examples of the several Army relevant biological targets for peptide-based sensing platforms include Ricin and Abrin. Ricin and Abrin are alarming threats because both can be weaponized and there is no antidote for exposure. Combining the sensitivity of SERS with the selectivity of a bifunctional peptide allows for the emergence of dynamic hazard sensor for Army application.

  10. The relevance of physicochemical and biological parameters for setting emission limit values for plants treating complex industrial wastewaters.

    PubMed

    Huybrechts, Diane; Weltens, Reinhilde; Jacobs, Griet; Borburgh, Ab; Smets, Toon; Hoebeke, Lut; Polders, Caroline

    2014-02-01

    The influents of plants treating complex industrial wastewaters from third parties may contain a large variety of often unknown or unidentified potentially harmful substances. The conventional approach of assessing and regulating the effluents of these plants is to set emission limit values for a limited set of physicochemical parameters, such as heavy metals, biological oxygen demand, chemical oxygen demand and adsorbable organic halogen compounds. The objective of this study was to evaluate the relevance of physicochemical parameters for setting emission limit values for such plants based on a comparison of effluent analyses by physicochemical and biological assessment tools. The results show that physicochemical parameters alone are not sufficient to evaluate the effectiveness of the water treatment plants for removing hazardous compounds and to protect the environment. The introduction of toxicity limits and limits for the total bioaccumulation potential should be considered to supplement generic parameters such as chemical oxygen demand and adsorbable organic halogens. A recommendation is made to include toxicity screening as a technique to consider in the determination of best available techniques (BAT) during the upcoming revision of the BAT reference document for the waste treatment industries to provide a more rational basis in decisions on additional treatment steps. PMID:24142491

  11. Metal-based antitumour drugs in the post-genomic era: what comes next?

    PubMed

    Sava, Gianni; Bergamo, Alberta; Dyson, Paul J

    2011-09-28

    In our Dalton Transactions Perspective article entitled, 'Metal-based antitumour drugs in the post genomic era', (Dalton Trans., 2006, 1929-1933) we discussed metal-based drugs in light of past decades of research. We concluded that the post-genomic era would dictate a change in the direction of the field with knowledge of the genome increasingly allowing protein targets to be identified and not simply assuming that DNA is the only relevant target of metal-based drugs. Since our article was published new insights into the mode of action of metal-based drugs have emerged making some older findings increasingly relevant to current drug design. In this article we discuss these developments in terms of what we believe should be the future direction for the field. PMID:21725573

  12. Functionally relevant microorganisms to enhanced biological phosphorus removal performance at full-scale wastewater treatment plants in the United States.

    PubMed

    Gu, April Z; Saunders, A; Neethling, J B; Stensel, H D; Blackall, L L

    2008-08-01

    The abundance and relevance ofAccumulibacter phosphatis (presumed to be polyphosphate-accumulating organisms [PAOs]), Competibacter phosphatis (presumed to be glycogen-accumulating organisms [GAOs]), and tetrad-forming organisms (TFOs) to phosphorus removal performance at six full-scale enhanced biological phosphorus removal (EBPR) wastewater treatment plants were investigated. Coexistence of various levels of candidate PAOs and GAOs were found at these facilities. Accumulibacter were found to be 5 to 20% of the total bacterial population, and Competibacter were 0 to 20% of the total bacteria population. The TFO abundance varied from nondetectable to dominant. Anaerobic phosphorus (P) release to acetate uptake ratios (P(rel)/HAc(up)) obtained from bench tests were correlated positively with the abundance ratio of Accumulibacter/(Competibacter +TFOs) and negatively with the abundance of (Competibacter +TFOs) for all plants except one, suggesting the relevance of these candidate organisms to EBPR processes. However, effluent phosphorus concentration, amount of phosphorus removed, and process stability in an EBPR system were not directly related to high PAO abundance or mutually exclusive with a high GAO fraction. The plant that had the lowest average effluent phosphorus and highest stability rating had the lowest P(rel)/HAc(up) and the most TFOs. Evaluation of full-scale EBPR performance data indicated that low effluent phosphorus concentration and high process stability are positively correlated with the influent readily biodegradable chemical oxygen demand-to-phosphorus ratio. A system-level carbon-distribution-based conceptual model is proposed for capturing the dynamic competition between PAOs and GAOs and their effect on an EBPR process, and the results from this study seem to support the model hypothesis. PMID:18751532

  13. Functionalization of manganite nanoparticles and their interaction with biologically relevant small ligands: Picosecond time-resolved FRET studies

    NASA Astrophysics Data System (ADS)

    Giri, Anupam; Makhal, Abhinandan; Ghosh, Barnali; Raychaudhuri, A. K.; Pal, Samir Kumar

    2010-12-01

    We report molecular functionalization of the promising manganite nanoparticles La0.67Sr0.33MnO3 (LSMO) for their solubilization in aqueous environments. The functionalization of individual NPs with the biocompatible citrate ligand, as confirmed by Fourier transform infrared (FTIR) spectroscopy, reveals that citrates are covalently attached to the surface of the NPs. UV-VIS spectroscopic studies on the citrate functionalized NPs reveals an optical band in the visible region. Uniform size selectivity (2.6 nm) of the functionalization process is confirmed from high resolution transmission electron microscope (HRTEM). In the present study we have used the optical band of the functionalized NPs to monitor their interaction with other biologically important ligands. Förster resonance energy transfer (FRET) of a covalently attached probe4-nitrophenylanthranilate (NPA) with the capped NPs confirm the attachment of the NPA ligands to the surface functional group (-OH) of the citrate ligand. The FRET of a DNA base mimic, 2-aminopurine (2AP), with the NPs confirms the surface adsorption of 2AP. Our study may find relevance in the study of the interaction of individual manganite NPs with drug/ligand molecules.We report molecular functionalization of the promising manganite nanoparticles La0.67Sr0.33MnO3 (LSMO) for their solubilization in aqueous environments. The functionalization of individual NPs with the biocompatible citrate ligand, as confirmed by Fourier transform infrared (FTIR) spectroscopy, reveals that citrates are covalently attached to the surface of the NPs. UV-VIS spectroscopic studies on the citrate functionalized NPs reveals an optical band in the visible region. Uniform size selectivity (2.6 nm) of the functionalization process is confirmed from high resolution transmission electron microscope (HRTEM). In the present study we have used the optical band of the functionalized NPs to monitor their interaction with other biologically important ligands. F

  14. Atypical behavior in the electron capture induced dissociation of biologically relevant transition metal ion complexes of the peptide hormone oxytocin

    NASA Astrophysics Data System (ADS)

    Kleinnijenhuis, Anne J.; Mihalca, Romulus; Heeren, Ron M. A.; Heck, Albert J. R.

    2006-07-01

    Doubly protonated ions of the disulfide bond containing nonapeptide hormone oxytocin and oxytocin complexes with different transition metal ions, that have biological relevance under physiological conditions, were subjected to electron capture dissociation (ECD) to probe their structural features in the gas phase. Although, all the ECD spectra were strikingly different, typical ECD behavior was observed for complexes of the nonapeptide hormone oxytocin with Ni2+, Co2+ and Zn2+, i.e., abundant c/z' and a'/y backbone cleavages and ECD characteristic S-S and S-C bond cleavages were observed. We propose that, although in the oxytocin-transition metal ion complexes the metal ions serve as the main initial capture site, the captured electron is transferred to other sites in the complex to form a hydrogen radical, which drives the subsequent typical ECD fragmentations. The complex of oxytocin with Cu2+ displayed noticeably different ECD behavior. The fragment ions were similar to fragment ions typically observed with low-energy collision induced dissociation (CID). We propose that the electrons captured by the oxytocin-Cu2+ complex might be favorably involved in reducing the Cu2+ metal ion to Cu+. Subsequent energy redistribution would explain the observed low-energy CID-type fragmentations. Electron capture resulted also in quite different specific cleavage sites for the complexes of oxytocin with Ni2+, Co2+ and Zn2+. This is an indication for structural differences in these complexes possibly linked to their significantly different biological effects on oxytocin-receptor binding, and suggests that ECD may be used to study subtle structural differences in transition metal ion-peptide complexes.

  15. Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles.

    PubMed

    Monopoli, Marco P; Walczyk, Dorota; Campbell, Abigail; Elia, Giuliano; Lynch, Iseult; Bombelli, Francesca Baldelli; Dawson, Kenneth A

    2011-03-01

    It is now clearly emerging that besides size and shape, the other primary defining element of nanoscale objects in biological media is their long-lived protein ("hard") corona. This corona may be expressed as a durable, stabilizing coating of the bare surface of nanoparticle (NP) monomers, or it may be reflected in different subpopulations of particle assemblies, each presenting a durable protein coating. Using the approach and concepts of physical chemistry, we relate studies on the composition of the protein corona at different plasma concentrations with structural data on the complexes both in situ and free from excess plasma. This enables a high degree of confidence in the meaning of the hard protein corona in a biological context. Here, we present the protein adsorption for two compositionally different NPs, namely sulfonated polystyrene and silica NPs. NP-protein complexes are characterized by differential centrifugal sedimentation, dynamic light scattering, and zeta-potential both in situ and once isolated from plasma as a function of the protein/NP surface area ratio. We then introduce a semiquantitative determination of their hard corona composition using one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray liquid chromatography mass spectrometry, which allows us to follow the total binding isotherms for the particles, identifying simultaneously the nature and amount of the most relevant proteins as a function of the plasma concentration. We find that the hard corona can evolve quite significantly as one passes from protein concentrations appropriate to in vitro cell studies to those present in in vivo studies, which has deep implications for in vitro-in vivo extrapolations and will require some consideration in the future. PMID:21288025

  16. Metal-Based Nanoparticles and the Immune System: Activation, Inflammation, and Potential Applications

    PubMed Central

    Luo, Yueh-Hsia; Chang, Louis W.; Lin, Pinpin

    2015-01-01

    Nanomaterials, including metal-based nanoparticles, are used for various biological and medical applications. However, metals affect immune functions in many animal species including humans. Different physical and chemical properties induce different cellular responses, such as cellular uptake and intracellular biodistribution, leading to the different immune responses. The goals of this review are to summarize and discuss the innate and adaptive immune responses triggered by metal-based nanoparticles in a variety of immune system models. PMID:26125021

  17. Generation of hydroxyl radical by chromate in biologically relevant systems: role of Cr(V) complexes versus tetraperoxochromate(V).

    PubMed

    Shi, X; Dalal, N S

    1994-09-01

    While Cr(V) species and .OH radicals have been suggested to play significant roles in the mechanism of chromate-related carcinogenesis, controversy still exists regarding the identity of the Cr(V) species and their role in the generation of .OH radicals. Some recent studies have suggested that the primary Cr(V) species involved is the tetraperoxochromate(V) (CrO8(3-)) ion, which produces .OH radical either on decomposition or by reaction with H2O2. The present study utilized ESR and spin trapping techniques to probe this mechanism. The results obtained show that (i) CrO8(3-) is not formed in any significant quantity in the reaction of chromate with biologically relevant reductants such as glutathione, glutathione reductase, NAD(P)H, ascorbate, vitamin B2, etc. (ii) Decomposition of CrO8(3-), or its reaction with H2O2 does not generate any significant amount of .OH radicals. (iii) The major Cr(V) species formed are complexes of Cr(V) with reductant moieties as ligands. (iv) These Cr(V) complexes generate .OH radicals from H2O2 via Fenton-like reaction. The present study thus disagrees with the recently proposed "tetraperoxochromate(V) theory of carcinogenesis from chromate." Instead, it suggests an alternative mechanism, which might be labeled as "the Cr(V)-complexation-Fenton reaction model of carcinogenesis from chromate. PMID:7843104

  18. A short-term colorectal cancer sphere culture as a relevant tool for human cancer biology investigation

    PubMed Central

    Weiswald, L-B; Richon, S; Massonnet, G; Guinebretière, J-M; Vacher, S; Laurendeau, I; Cottu, P; Marangoni, E; Nemati, F; Validire, P; Bellet, D; Bièche, I; Dangles-Marie, V

    2013-01-01

    Background: Ex vivo colospheres have been previously characterised as a colorectal cancer (CRC) well-rounded multicellular model, exclusively formed by carcinoma cells, and derived from fresh CRC tissue after mechanical dissociation. The ability to form colospheres was correlated with tumour aggressiveness. Their three-dimensional conformation prompted us to further investigate their potential interest as a preclinical cancer tool. Methods: Patient-derived CRC xenografts were used to produce numerous colospheres. Mechanism of formation was elucidated by confocal microscopy. Expression analysis of a panel of 64 selected cancer-related genes by real-time qRT–PCR and hierarchical clustering allowed comparison of colospheres with parent xenografts. In vitro and in vivo assays were performed for migration and chemosensitivity studies. Results: Colospheres, formed by tissue remodelling and compaction, remained viable several weeks in floating conditions, escaping anoikis through their strong cell–cell interactions. Colospheres matched the gene expression profile of the parent xenograft tissue. Colosphere-forming cells migrated in collagen I matrix and metastasised when subrenally implanted in nude mice. Besides, the colosphere responses to 5-fluorouracil and irinotecan, two standard drugs in CRC, reproduced those of the in vivo original xenografts. Conclusion: Colospheres closely mimic biological characteristics of in vivo CRC tumours. Consequently, they would be relevant ex vivo CRC models. PMID:23538387

  19. Alkali Metal Ion Complexes with Phosphates, Nucleotides, Amino Acids, and Related Ligands of Biological Relevance. Their Properties in Solution.

    PubMed

    Crea, Francesco; De Stefano, Concetta; Foti, Claudia; Lando, Gabriele; Milea, Demetrio; Sammartano, Silvio

    2016-01-01

    Alkali metal ions play very important roles in all biological systems, some of them are essential for life. Their concentration depends on several physiological factors and is very variable. For example, sodium concentrations in human fluids vary from quite low (e.g., 8.2 mmol dm(-3) in mature maternal milk) to high values (0.14 mol dm(-3) in blood plasma). While many data on the concentration of Na(+) and K(+) in various fluids are available, the information on other alkali metal cations is scarce. Since many vital functions depend on the network of interactions occurring in various biofluids, this chapter reviews their complex formation with phosphates, nucleotides, amino acids, and related ligands of biological relevance. Literature data on this topic are quite rare if compared to other cations. Generally, the stability of alkali metal ion complexes of organic and inorganic ligands is rather low (usually log K < 2) and depends on the charge of the ligand, owing to the ionic nature of the interactions. At the same time, the size of the cation is an important factor that influences the stability: very often, but not always (e.g., for sulfate), it follows the trend Li(+) > Na(+) > K(+) > Rb(+) > Cs(+). For example, for citrate it is: log K ML = 0.88, 0.80, 0.48, 0.38, and 0.13 at 25 °C and infinite dilution. Some considerations are made on the main aspects related to the difficulties in the determination of weak complexes. The importance of the alkali metal ion complexes was also studied in the light of modelling natural fluids and in the use of these cations as probes for different processes. Some empirical relationships are proposed for the dependence of the stability constants of Na(+) complexes on the ligand charge, as well as for correlations among log K values of NaL, KL or LiL species (L = generic ligand). PMID:26860301

  20. The effect of anaesthetics on the properties of a lipid membrane in the biologically relevant phase: a computer simulation study.

    PubMed

    Fábián, Balázs; Darvas, Mária; Picaud, Sylvain; Sega, Marcello; Jedlovszky, Pál

    2015-06-14

    Molecular dynamics simulations of the fully hydrated neat dipalmitoylphosphatidylcholine (DPPC) membrane as well as DPPC membranes containing four different general anaesthetic molecules, namely chloroform, halothane, diethyl ether and enflurane, have been simulated at two different pressures, i.e., at 1 bar and 1000 bar, at the temperature of 310 K. At this temperature the model used in this study is known to be in the biologically most relevant liquid crystalline (Lα) phase. To find out which properties of the membrane might possibly be related to the molecular mechanism of anaesthesia, we have been looking for properties that change in the same way in the presence of any general anaesthetic molecule, and change in the opposite way by the increase of pressure. This way, we have ruled out the density distribution of various groups along the membrane normal axis, orientation of the lipid heads and tails, self-association of the anaesthetics, as well as the local order of the lipid tails as possible molecular reasons of anaesthesia. On the other hand, we have found that the molecular surface area, and hence also the molecular volume of the membrane, is increased by the presence of any anaesthetic molecule, and decreased by the pressure, in accordance with the more than half a century old critical volume hypothesis. We have also found that anaesthetic molecules prefer two different positions along the membrane normal axis, namely the middle of the membrane and the outer edge of the hydrocarbon region, close to the polar headgroups. The increase of pressure is found to decrease the former, and increase the latter preference, and hence it might also be related to the pressure reversal of anaesthesia. PMID:25975364

  1. UV and skin cancer: specific p53 gene mutation in normal skin as a biologically relevant exposure measurement.

    PubMed Central

    Nakazawa, H; English, D; Randell, P L; Nakazawa, K; Martel, N; Armstrong, B K; Yamasaki, H

    1994-01-01

    Many human skin tumors contain mutated p53 genes that probably result from UV exposure. To investigate the link between UV exposure and p53 gene mutation, we developed two methods to detect presumptive UV-specific p53 gene mutations in UV-exposed normal skin. The methods are based on mutant allele-specific PCRs and ligase chain reactions and designed to detect CC to TT mutations at codons 245 and 247/248, using 10 micrograms of DNA samples. These specific mutations in the p53 gene have been reported in skin tumors. CC to TT mutations in the p53 gene were detected in cultured human skin cells only after UV irradiation, and the mutation frequency increased with increasing UV dose. Seventeen of 23 samples of normal skin from sun-exposed sites (74%) on Australian skin cancer patients contained CC to TT mutations in one or both of codons 245 and 247/248 of the p53 gene, and only 1 of 20 samples from non-sun-exposed sites (5%) harbored the mutation. None of 15 biopsies of normal skin from non-sun-exposed or intermittently exposed sites on volunteers living in France carried such mutations. Our results suggest that specific p53 gene mutations associated with human skin cancer are induced in normal skin by solar UV radiation. Measurement of these mutations may be useful as a biologically relevant measure of UV exposure in humans and as a possible predictor of risk for skin cancer. Images Fig. 2 Fig. 3 Fig. 4 PMID:8278394

  2. V-type nerve agents phosphonylate ubiquitin at biologically relevant lysine residues and induce intramolecular cyclization by an isopeptide bond.

    PubMed

    Schmidt, Christian; Breyer, Felicitas; Blum, Marc-Michael; Thiermann, Horst; Worek, Franz; John, Harald

    2014-08-01

    Toxic organophosphorus compounds (e.g., pesticides and nerve agents) are known to react with nucleophilic side chains of different amino acids (phosphylation), thus forming adducts with endogenous proteins. Most often binding to serine, tyrosine, or threonine residues is described as being of relevance for toxicological effects (e.g., acetylcholinesterase and neuropathy target esterase) or as biomarkers for post-exposure analysis (verification, e.g., albumin and butyrylcholinesterase). Accordingly, identification of novel protein targets might be beneficial for a better understanding of the toxicology of these compounds, revealing new bioanalytical verification tools, and improving knowledge on chemical reactivity. In the present study, we investigated the reaction of ubiquitin (Ub) with the V-type nerve agents Chinese VX, Russian VX, and VX in vitro. Ub is a ubiquitous protein with a mass of 8564.8 Da present in the extra- and intracellular space that plays an important physiological role in several essential processes (e.g., proteasomal degradation, DNA repair, protein turnover, and endocytosis). Reaction products were analyzed by matrix-assisted laser desorption/ionization-time-of-flight- mass spectrometry (MALDI-TOF MS) and μ-high-performance liquid chromatography online coupled to UV-detection and electrospray ionization MS (μHPLC-UV/ESI MS). Our results originally document that a complex mixture of at least mono-, di, and triphosphonylated Ub adducts was produced. Surprisingly, peptide mass fingerprint analysis in combination with MALDI and ESI MS/MS revealed that phosphonylation occurred with high selectivity in at least 6 of 7 surface-exposed lysine residues that are essential for the biological function of Ub. These reaction products were found not to age. In addition, we herein report for the first time that phosphonylation induced intramolecular cyclization by formation of an isopeptide bond between the ε-amino group of a formerly phosphonylated

  3. Design, Development, and Psychometric Analysis of a General, Organic, and Biological Chemistry Topic Inventory Based on the Identified Main Chemistry Topics Relevant to Nursing Clinical Practice

    ERIC Educational Resources Information Center

    Brown, Corina E.

    2013-01-01

    This two-stage study focused on the undergraduate nursing course that covers topics in general, organic, and biological (GOB) chemistry. In the first stage, the central objective was to identify the main concepts of GOB chemistry relevant to the clinical practice of nursing. The collection of data was based on open-ended interviews of both nursing…

  4. Dose addition models based on biologically-relevant reductions in fetal testosterone accurately predict postnatal reproductive tract alterations by a phthalate mixture in rats

    EPA Science Inventory

    Challenges in cumulative risk assessment of anti-androgenic phthalate mixtures include a lack of data on all the individual phthalates and difficulty determining the biological relevance of reduction in fetal testosterone (T) on postnatal development. The objectives of the curren...

  5. Establishing the "Biological Relevance" of Dipentyl Phthalate Reductions in Fetal Rat Testosterone Production and Plasma and Testis Testosterone Levels.

    PubMed

    Gray, Leon Earl; Furr, Johnathan; Tatum-Gibbs, Katoria R; Lambright, Christy; Sampson, Hunter; Hannas, Bethany R; Wilson, Vickie S; Hotchkiss, Andrew; Foster, Paul M D

    2016-01-01

    Phthalate esters (PEs) constitute a large class of compounds that are used for many consumer product applications. Many of the C2-C7 di-ortho PEs reduce fetal testicular hormone and gene expression levels in rats resulting in adverse effects seen later in life but it appears that relatively large reductions in fetal testosterone (T) levels and testis gene expression may be required to adversely affect reproductive development (Hannas, B. R., Lambright, C. S., Furr, J., Evans, N., Foster, P. M., Gray, E. L., and Wilson, V. S. (2012). Genomic biomarkers of phthalate-induced male reproductive developmental toxicity: a targeted RT-PCR array approach for defining relative potency. Toxicol. Sci. 125, 544-557). The objectives of this study were (1) to model the relationships between changes in fetal male rat plasma testosterone (PT), T levels in the testis (TT), T production (PROD), and testis gene expression with the reproductive malformation rates, and (2) to quantify the "biologically relevant reductions" (BRRs) in fetal T necessary to induce adverse effects in the offspring. In the fetal experiment, Harlan Sprague-Dawley rats were dosed with dipentyl phthalate (DPeP) at 0, 11, 33, 100, and 300 mg/kg/day from gestational days (GD) 14-18 and fetal testicular T, PT levels, and T Prod and gene expression were assessed on GD 18. In the postnatal experiment, rats were dosed with DPeP from GD 8-18 and reproductive development was monitored through adulthood. The dose-response curves for TT levels (ED(50) = 53 mg/kg) and T PROD (ED(50) = 45 mg/kg) were similar, whereas PT was reduced at ED50 = 19 mg/kg. When the reductions in TPROD and Insl3 mRNA were compared with the postnatal effects of in utero DPeP, dose-related reproductive alterations were noted when T PROD and Insl3 mRNA were reduced by >45% and 42%, respectively. The determination of BRR levels may enable risk assessors to utilize fetal endocrine data to help establish points of departure for

  6. "Evo in the News": A Pedagogical Tool to Enhance Students' Perceptions of the Relevance of Evolutionary Biology

    ERIC Educational Resources Information Center

    Infanti, Lynn M.

    2012-01-01

    This investigation evaluated the effects of the use of the pedagogical tool "Evo in the News" on the attitudes toward and knowledge of biological evolution in a sample of undergraduate non-major biology students at a large, private research university. In addition, this study looked at the initial attitudes of the students and their…

  7. Hydration Structures and Thermodynamic Properties of Cationized Biologically Relevant Molecules, M+(Indole)(H2O)n (M = Na, K; n = 3-6)

    NASA Astrophysics Data System (ADS)

    Ke, Haochen; Lisy, James

    2015-03-01

    The balance between various noncovalent interactions plays a key role in determining the hydration structures and thermodynamic properties of biologically relevant molecules in biological mediums. Such properties of biologically relevant molecules are closely related to their often unique biological functionalities. The indole moiety is a basic functional group of many important neurotransmitters and hormones and has been used as tractable model for more complex biomolecules. The cationized indole water cluster is a perfect system for the quantitative and systematic study of the competition and cooperation of noncovalent interactions, as electrostatic interactions can be adjusted by introducing different monovalent cations and hydrogen bonding interactions can be adjusted by varying the level of hydration. IRPD spectra with isotopic (H/D) analysis helped unravel the overlapping N-H and O-H stretching modes, a major challenge of earlier studies. Thermodynamic analysis using relative Gibbs free energies, for energy ordering, together with spectral analysis provided unambiguous assignment of spectral features and structural configurations. A systematic hydration model with an in-depth account of noncovalent interactions is presented.

  8. Modeling pCO{sub 2} in the upper ocean: A review of relevant physical, chemical, and biological processes

    SciTech Connect

    1990-12-01

    The pCO{sub 2} of the surface ocean is controlled by a combination of physical, chemical, and biological processes. Modeling surface ocean pCO{sub 2} is analogous to modeling sea surface temperature (SST), in that sea surface pCO{sub 2} is affected by fluxes across the air-sea interface and by exchange with deeper water. However, pCO{sub 2} is also affected by chemical and biological processes which have no analog in SST. Seawater pCO{sub 2} is buffered by pH equilibrium reactions between the species CO{sub 2}, HCO{sub 3}-, and CO{sub 3}{sup =}. This effect provides an effective reservoir for CO{sub 2} in seawater that is 10 times larger than it would be for an unbuffered gas. The equilibrium between dissolved and atmospheric CO{sub 2} is sensitive to temperature, tending to higher pCO{sub 2} in warmer water. Biological export of carbon as sinking particles maintains a gradient of pCO{sub 2}, with lower values near the surface (this processes is called the {open_quotes}biological pump{close_quotes}). In most of the ocean, biological activity removes all of the available nutrients from the surface water; that is, the rate of carbon export in these locations is limited by the rate of nutrient supply to the euphotic zone. However, in much of the high-latitude oceans, primary production does not deplete the euphotic zone of nutrients, a fact to which the atmospheric pCO{sub 2} is extraordinarily sensitive. Understanding the limits to phytoplankton growth in the high latitudes, and how these limits might change under different climatic regimes, is essential to prediction of future ocean uptake of fossil fuel CO{sub 2}.

  9. Classical conditioning of sexual arousal in women and men: effects of varying awareness and biological relevance of the conditioned stimulus.

    PubMed

    Hoffmann, Heather; Janssen, Erick; Turner, Stefanie L

    2004-02-01

    Classical conditioning of sexual arousal has previously been demonstrated in human males but not in females. This study explored the role of classical (Pavlovian) conditioning in the activation of genital sexual arousal in both women and men, and assessed the effects of varying conditioned stimulus (CS) duration (subliminal/conscious) and relevance (sexually relevant/irrelevant). Twenty-seven female and 29 male participants received either subliminal or conscious presentations of a photograph of either a sexually relevant (abdomen of the opposite sex) or irrelevant (gun) CS+, which was followed by the unconditioned stimulus (US-erotic film clip). A CS-, a stimulus not paired with the US, was also included in the 11 conditioning trials. Ten participants were assigned to a control group that received unpaired presentations of the CS+, CS-, and the US. Both women and men showed more evidence of conditioning to the abdomen than to the gun when the CS was presented subliminally. When consciously perceived CSs were used, however, gender differences emerged. Men again showed the expected cue-to-consequence specificity but women showed the opposite effect, that is, conditioned arousal to the sexually irrelevant rather than to the relevant CS. The latter finding may be due to increased autonomic nervous system arousal associated with the irrelevant CS (gun). Skin conductance responses indicated more general arousal to the gun than to the male abdomen in women. This is the first study to compare the effects of a subliminal and conscious CS and to find classical conditioning of sexual arousal in women. PMID:14739689

  10. Evaluating emotional sensitivity and tolerance factors in the prediction of panic-relevant responding to a biological challenge.

    PubMed

    Kutz, Amanda; Marshall, Erin; Bernstein, Amit; Zvolensky, Michael J

    2010-01-01

    The current study investigated anxiety sensitivity, distress tolerance (Simons & Gaher, 2005), and discomfort intolerance (Schmidt, Richey, Cromer, & Buckner, 2007) in relation to panic-relevant responding (i.e., panic attack symptoms and panic-relevant cognitions) to a 10% carbon dioxide enriched air challenge. Participants were 216 adults (52.6% female; M(age)=22.4, SD=9.0). A series of hierarchical multiple regressions was conducted with covariates of negative affectivity and past year panic attack history in step one of the model, and anxiety sensitivity, discomfort intolerance, and distress tolerance entered simultaneously into step two. Results indicated that anxiety sensitivity, but not distress tolerance or discomfort intolerance, was significantly incrementally predictive of physical panic attack symptoms and cognitive panic attack symptoms. Additionally, anxiety sensitivity was significantly predictive of variance in panic attack status during the challenge. These findings emphasize the important, unique role of anxiety sensitivity in predicting risk for panic psychopathology, even when considered in the context of other theoretically relevant emotion vulnerability variables. PMID:19720496

  11. Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives.

    PubMed

    Šegan, Sandra; Trifković, Jelena; Verbić, Tatjana; Opsenica, Dejan; Zlatović, Mario; Burnett, James; Šolaja, Bogdan; Milojković-Opsenica, Dušanka

    2013-01-01

    The physicochemical properties, retention parameters (R(M)(0)), partition coefficients (logP(OW)), and pK(a) values for a series of thirteen 1,7-bis(aminoalkyl) diazachrysene (1,7-DAAC) derivatives were determined in order to reveal the characteristics responsible for their biological behavior. The investigated compounds inhibit three unrelated pathogens (the Botulinum neurotoxin serotype A light chain (BoNT/A LC), Plasmodium falciparum malaria, and Ebola filovirus) via three different mechanisms of action. To determine the most influential factors governing the retention and activities of the investigated diazachrysenes, R(M)(0), logP(OW), and biological activity values were correlated with 2D and 3D molecular descriptors, using a partial least squares regression. The resulting quantitative structure-retention (property) relationships indicate the importance of descriptors related to the hydrophobicity of the molecules (e.g., predicted partition coefficients and hydrophobic surface area). Quantitative structure-activity relationship models for describing biological activity against the BoNT/A LC and malarial strains also include overall compound polarity, electron density distribution, and proton donor/acceptor potential. Furthermore, models for Ebola filovirus inhibition are presented qualitatively to provide insights into parameters that may contribute to the compounds' antiviral activities. Overall, the models form the basis for selecting structural features that significantly affect the compound's absorption, distribution, metabolism, excretion, and toxicity profiles. PMID:22985530

  12. Effect of Co-Existing Biologically Relevant Molecules and Ions on DNA Photocleavage Caused by Pyrene and its Derivatives

    PubMed Central

    Wang, Shuguang; Yu, Hongtao

    2005-01-01

    Inorganic ions, coenzymes, amino acids, and saccharides could co-exist with toxic environmental chemicals, such as polycyclic aromatic hydrocarbons (PAHs), in the cell. The presence of these co-existing chemicals can modulate the toxicity of the PAHs. One of the genotoxic effects by PAHs is light-induced cleavage, or photocleavage, of DNA. The effect of inorganic ions I−, Na+, Ca2+, Mg2+, Fe3+, Mn2+, Cu2+, and Zn2+ and biological molecules riboflavin, histidine, mannitol, nicotinamide adenine dinucleotide (NAD), glutathione, and glutamic acid on the DNA photocleavage by pyrene, 1-hydroxypyrene (1-HP), and 1-aminopyrene (1-AP), is studied. The non-transition metal ions Na+, Ca2+, and Mg2+, usually have very little inhibitory effects, while the transition metal ions Fe3+, Cu2+, and Zn2+ enhance, Mn2+ inhibits the DNA photocleavage. The effect by biological molecules is complex, depending on the photochemical reaction mechanisms of the compounds tested (1-AP, 1-HP and pyrene) and on the chemical nature of the added biological molecules. Riboflavin, histidine, and mannitol enhance DNA photocleavage by all three compounds, except that mannitol has no effect on the photocleavage of DNA by pyrene. Glutathione inhibits the DNA photocleavage by 1-AP and 1-HP, but has no effect on that by pyrene. NAD enhances the DNA photocleavage by 1-AP, but has no effect on that by 1-HP and pyrene. Glutamic acid enhances the DNA photocleavage by 1-AP and pyrene, but inhibits that by 1-HP. These results show that the co-existing chemicals may have a profound effect on the toxicity of PAHs, or possibly on the toxicity of many other chemicals. Therefore, if one studies the toxic effects of PAHs or other toxic chemicals, the effect of the co-existing chemicals or ions needs to be considered. PMID:16705811

  13. SysBioCube: A Data Warehouse and Integrative Data Analysis Platform Facilitating Systems Biology Studies of Disorders of Military Relevance.

    PubMed

    Chowbina, Sudhir; Hammamieh, Rasha; Kumar, Raina; Chakraborty, Nabarun; Yang, Ruoting; Mudunuri, Uma; Jett, Marti; Palma, Joseph M; Stephens, Robert

    2013-01-01

    SysBioCube is an integrated data warehouse and analysis platform for experimental data relating to diseases of military relevance developed for the US Army Medical Research and Materiel Command Systems Biology Enterprise (SBE). It brings together, under a single database environment, pathophysio-, psychological, molecular and biochemical data from mouse models of post-traumatic stress disorder and (pre-) clinical data from human PTSD patients.. SysBioCube will organize, centralize and normalize this data and provide an access portal for subsequent analysis to the SBE. It provides new or expanded browsing, querying and visualization to provide better understanding of the systems biology of PTSD, all brought about through the integrated environment. We employ Oracle database technology to store the data using an integrated hierarchical database schema design. The web interface provides researchers with systematic information and option to interrogate the profiles of pan-omics component across different data types, experimental designs and other covariates. PMID:24303294

  14. Neocryptolepine: A Promising Indoloisoquinoline Alkaloid with Interesting Biological Activity. Evaluation of the Drug and its Most Relevant Analogs.

    PubMed

    Larghi, Enrique L; Bracca, Andrea B J; Arroyo Aguilar, Abel A; Heredia, Daniel A; Pergomet, Jorgelina L; Simonetti, Sebastian O; Kaufman, Teodoro S

    2015-01-01

    Plants are one of the most important resources for the discovery of new drugs. The potential of natural compounds as new drug leads is clearly illustrated by the discovery and development of many modern medicines. This is an encouraging factor that drives natural products research in the vegetable kingdom. Neocryptolepine is a tetracyclic nitrogen heterocycle isolated from the African climber Cryptolepis sanguinolenta, which is widely used in traditional African medicine in many countries of Central and West Africa. The natural product is one of the representative examples of the small family of indolo[2,3-b]quinoline alkaloids, being endowed of multiple biological activities, including DNA-binding and inhibition of the enzyme topoisomerase II. It is also cytotoxic, antibacterial, antifungal and molluscicidal, also displaying antiprotozoal activity, particularly as antitrypanosomal, antileishmanial, antischistosomal and antiplasmodial. Some of these activities have been related to the product's ability to bind to DNA and to inhibit topoisomerase II; however, the exact mechanisms behind all of the observed bioactivities have not been comprehensively clarified. Major research activities regarding neocryptolepine have been focused into two seemingly opposite fields, related to its cytotoxic and antimalarial properties. Optimization of the natural product as a cytotoxic agent implied improvements in its bioavailability and activity, while the need of non-cytotoxic compounds guided the design and optimization of antimalarial agents. Therefore, the aim of the present article is to systematically review the current knowledge about the diversity of the biological activities related to neocryptolepine, its analogs and derivatives. PMID:25915612

  15. A Heteroepitaxial Perovskite Metal-Base Transistor

    SciTech Connect

    Yajima, T.; Hikita, Y.; Hwang, H.Y.; /Tokyo U. /JST, PRESTO /SLAC

    2011-08-11

    'More than Moore' captures a concept for overcoming limitations in silicon electronics by incorporating new functionalities in the constituent materials. Perovskite oxides are candidates because of their vast array of physical properties in a common structure. They also enable new electronic devices based on strongly-correlated electrons. The field effect transistor and its derivatives have been the principal oxide devices investigated thus far, but another option is available in a different geometry: if the current is perpendicular to the interface, the strong internal electric fields generated at back-to-back heterojunctions can be used for oxide electronics, analogous to bipolar transistors. Here we demonstrate a perovskite heteroepitaxial metal-base transistor operating at room temperature, enabled by interface dipole engineering. Analysis of many devices quantifies the evolution from hot-electron to permeable-base behaviour. This device provides a platform for incorporating the exotic ground states of perovskite oxides, as well as novel electronic phases at their interfaces.

  16. Emotional interference-based forgetting in short-term memory. Cognitive inhibition of pleasant but not unpleasant biologically relevant distractors

    PubMed Central

    García-Pacios, Javier; Del Río, David; Villalobos, Dolores; Ruiz-Vargas, José M.; Maestú, Fernando

    2015-01-01

    Emotional stimuli automatically recruit attentional resources. Although this usually brings more adaptive responses, it may suppose a disadvantage when emotional information is task-irrelevant and should be ignored. Previous studies have shown how emotional stimuli with a negative content exert a greater interference than neutral stimuli during a concurrent working memory (WM) task. However, the impact of positively valenced stimuli as interference has not been addressed to date. In three experiments and one re-analysis we explore the impact of pleasant and unpleasant emotional distractors during WM maintenance. The results suggest that our cognitive control can cope with the interference posed by pleasant distractors as well as with the interference posed by neutral stimuli. However, unpleasant distractors are harder to control in the context of WM maintenance. As unpleasant stimuli usually convey relevant information that we should not to ignore, our executive control seems to be less able to reallocate cognitive resources after unpleasant distraction. PMID:25999894

  17. Improving biological relevancy of transcriptional biomarkers experiments by applying the MIQE guidelines to pre-clinical and clinical trials.

    PubMed

    Dooms, M; Chango, A; Barbour, E; Pouillart, P; Abdel Nour, A M

    2013-01-01

    The "Minimum Information for the Publication of qPCR Experiments" (MIQE [3]) guidelines are very much targeted at basic research experiments and have to our knowledge not been applied to qPCR assays carried out in the context of clinical trials. This report details the use of the MIQE qPCR app for iPhone (App Store, Apple) to assess the MIQE compliance of one clinical and five pre-clinical trials. This resulted in the need to include 14 modifications that make the guidelines more relevant for the assessment of this special type of application. We also discuss the need for flexibility, since while some parameters increase experimental quality, they also require more reagents and more time, which is not always feasible in a clinical setting. PMID:22910527

  18. Predictive variables for the biological behaviour of basal cell carcinoma of the face: relevance of morphometry of the nuclei.

    PubMed

    Appel, T; Bierhoff, E; Appel, K; von Lindern, J-J; Bergé, S; Niederhagen, B

    2003-06-01

    We did a morphometric analysis of 130 histological sections of basal cell carcinoma (BCC) of the face to find out whether morphometric variables in the structure of the nuclei of BCC cells could serve as predictors of the biological behaviour. We considered the following variables: maximum and minimum diameters, perimeter, nuclear area and five form factors that characterise and quantify the shape of a structure (axis ratio, shape factor, nuclear contour index, nuclear roundness and circumference ratio). We did a statistical analysis of primary and recurring tumours and four histology-based groups (multifocal superficial BCCs, nodular BCCs, sclerosing BCCs and miscellaneous forms) using a two-sided t test for independent samples. Multifocal superficial BCCs showed significantly smaller values for the directly measured variables (maximum and minimum diameters, perimeter and nuclear area). Morphometry could not distinguish between primary and recurring tumours. PMID:12804537

  19. Biological Production of a Hydrocarbon Fuel Intermediate Polyhydroxybutyrate (PHB) from a Process Relevant Lignocellulosic Derived Sugar (Poster)

    SciTech Connect

    Wang, W.; Mittal, A.; Mohagheghi, A.; Johnson, D. K.

    2014-04-01

    PHAs are synthesized by many microorganisms to serve as intracellular carbon storage molecules. In some bacterial strains, PHB can account for up to 80% of cell mass. In addition to its application in the packaging sector, PHB also has great potential as an intermediate in the production of hydrocarbon fuels. PHB can be thermally depolymerized and decarboxylated to propene which can be upgraded to hydrocarbon fuels via commercial oligomerization technologies. Cupriavidus necator is the microorganism that has been most extensively studied and used for PHB production on an industrial scale; However the substrates used for producing PHB are mainly fructose, glucose, sucrose, fatty acids, glycerol, etc., which are expensive. In this study, we demonstrate production of PHB from a process relevant lignocellulosic derived sugar stream, i.e., saccharified slurry from pretreated corn stover. The strain was first investigated in shake flasks for its ability to utilize glucose, xylose and acetate. In addition, the strain was also grown on pretreated lignocellulose hydrolyzate slurry and evaluated in terms of cell growth, sugar utilization, PHB accumulation, etc. The mechanism of inhibition in the toxic hydrolysate generated by the pretreatment and saccharification process of biomass, was also studied.

  20. Identification of Genes Relevant to Pesticides and Biology from Global Transcriptome Data of Monochamus alternatus Hope (Coleoptera: Cerambycidae) Larvae

    PubMed Central

    Shao, Ensi; Rebeca, Carballar-Lejarazú; Guo, Yajie; Xiong, Yueting; Mou, Yani; Xu, Runxue; Hu, Xia; Liang, Guanghong; Zou, Shuangquan; Guan, Xiong; Zhang, Feiping

    2016-01-01

    Monochamus alternatus Hope is the main vector in China of the Pine Wilt Disease caused by the pine wood nematode Bursaphelenchus xylophilus. Although chemical control is traditionally used to prevent pine wilt disease, new strategies based in biological control are promising ways for the management of the disease. However, there is no deep sequence analysis of Monochamus alternatus Hope that describes the transcriptome and no information is available about gene function of this insect vector. We used next generation sequencing technology to sequence the whole fourth instar larva transcriptome of Monochamus alternatus Hope and successfully built a Monochamus alternatus Hope transcriptome database. In total, 105,612 unigenes were assigned for Gene Ontology (GO) terms, information for 16,730 classified unigenes was obtained in the Clusters of Orthologous Groups (COGs) database, and 13,024 unigenes matched with 224 predicted pathways in the Kyoto Encyclopedia of Genes and Genome (KEGG). In addition, genes related to putative insecticide resistance-related genes, RNAi, the Bt receptor, intestinal digestive enzymes, possible future insect control targets and immune-related molecules are described. This study provides valuable basic information that can be used as a gateway to develop new molecular tools for Monochamus alternatus Hope control strategies. PMID:26815657

  1. The nonconservative property of dissolved molybdenum in the western Taiwan Strait: Relevance of submarine groundwater discharges and biological utilization

    NASA Astrophysics Data System (ADS)

    Wang, Deli; Xia, Weiwei; Lu, Shuimiao; Wang, Guizhi; Liu, Qian; Moore, Willard S.; Arthur Chen, Chen-Tung

    2016-01-01

    This study examined dissolved Mo and sedimentary Mo along with hydrochemical parameters in the western Taiwan Strait (WTS) in May and August 2012. The results demonstrate that dissolved Mo could be depleted of as high as 10-20 nM during our May sampling period when the nutrient-enriched Min-Zhe coastal current ceased and spring blooms developed. The negative correlation between Chl-a and dissolved Mo suggests the possible involvement of high algal productivity in removing dissolved Mo out of the water column. Specific oceanographic settings (little currents) permitted a high sedimentary enrichment of Mo (>6 µg/g Mo) within the highly productive waters outside the Jiulong River mouth. Possibly, the high algal productivities and consequent organic matter sinks provide a pathway of Mo burial from water columns into sediments. Dissolved Mo was relatively high in groundwater samples, but we observed that submarine groundwater discharges (SGDs) only contributed to a relatively small percentage of the total dissolved Mo pool in WTS. It is probably attributable to the immediate removal of SGD-released Mo ions via adsorption onto newly formed Mn oxides once exposed to oxygenated seawater, followed by an elevated sedimentary Mo accumulation near the SGDs (˜5 µg/g). In addition to metal oxide particle scavenging and sulfide precipitation, we estimated that biological uptake along with Mo adsorption onto organic matter carriers could finally provide more than 10% of the annual sedimentary Mo accumulation in WTS.

  2. Head and neck cancer subtypes with biological and clinical relevance: Meta-analysis of gene-expression data.

    PubMed

    De Cecco, Loris; Nicolau, Monica; Giannoccaro, Marco; Daidone, Maria Grazia; Bossi, Paolo; Locati, Laura; Licitra, Lisa; Canevari, Silvana

    2015-04-20

    Head and neck squamous cell carcinoma (HNSCC) is a disease with heterogeneous clinical behavior and response to therapies. Despite the introduction of multimodality treatment, 40-50% of patients with advanced disease recur. Therefore, there is an urgent need to improve the classification beyond the current parameters in clinical use to better stratify patients and the therapeutic approaches. Following a meta-analysis approach we built a large training set to whom we applied a Disease-Specific Genomic Analysis (DSGA) to identify the disease component embedded into the tumor data. Eleven independent microarray datasets were used as validation sets. Six different HNSCC subtypes that summarize the aberrant alterations occurring during tumor progression were identified. Based on their main biological characteristics and de-regulated signaling pathways, the subtypes were designed as immunoreactive, inflammatory, human papilloma virus (HPV)-like, classical, hypoxia associated, and mesenchymal. Our findings highlighted a more aggressive behavior for mesenchymal and hypoxia-associated subtypes. The Genomics Drug Sensitivity Project was used to identify potential associations with drug sensitivity and significant differences were observed among the six subtypes. To conclude, we report a robust molecularly defined subtype classification in HNSCC that can improve patient selection and pave the way to the development of appropriate therapeutic strategies. PMID:25821127

  3. Relevance of Hydrodynamic Effects for the Calculation of Outer Surface Potential of Biological Membrane Using Electrophoretic Data.

    PubMed

    Silva, Izan M; Castro, Maria Clícia S; Silva, Dilson; Cortez, Célia M

    2016-06-01

    In this paper, we present the results of a study on the influence of hydrodynamic effects on the surface potentials of the erythrocyte membrane, comparing two different models formulated to simulate the electrophoretic movement of a biological cell: the classical Helmholtz-Smoluchowski model and a model presented by Hsu et al. (1996). This model considers hydrodynamic effects to describe the distribution of the fluid velocity. The electric potential equation was obtained from the non-linear Poisson-Boltzmann equation, considering the spatial distribution of electrical charges fixed in glycocalyx and cytoplasmic proteins, as well as electrolyte charges and ones fixed on the surfaces of lipidic bilayer. Our results show that the Helmholtz-Smoluchowski model is not able to reflect the real forces responsible to the electrophoretic behavior of cell, because it does not take account the hydrodynamic effects of glycocalyx. This charged network that covers cellular surface constitutes a complex physical system whose electromechanical characteristics cannot be neglected. Then, supporting the hypothesis of other authors, we suggest that, in electrophoretic motion analyses of cells, the classical model represents a limiting case of models that take into account hydrodynamic effects to describe the velocity distribution of fluid. PMID:27276378

  4. Identification of Genes Relevant to Pesticides and Biology from Global Transcriptome Data of Monochamus alternatus Hope (Coleoptera: Cerambycidae) Larvae.

    PubMed

    Wu, Songqing; Zhu, Xiaoli; Liu, Zhaoxia; Shao, Ensi; Rebeca, Carballar-Lejarazú; Guo, Yajie; Xiong, Yueting; Mou, Yani; Xu, Runxue; Hu, Xia; Liang, Guanghong; Zou, Shuangquan; Guan, Xiong; Zhang, Feiping

    2016-01-01

    Monochamus alternatus Hope is the main vector in China of the Pine Wilt Disease caused by the pine wood nematode Bursaphelenchus xylophilus. Although chemical control is traditionally used to prevent pine wilt disease, new strategies based in biological control are promising ways for the management of the disease. However, there is no deep sequence analysis of Monochamus alternatus Hope that describes the transcriptome and no information is available about gene function of this insect vector. We used next generation sequencing technology to sequence the whole fourth instar larva transcriptome of Monochamus alternatus Hope and successfully built a Monochamus alternatus Hope transcriptome database. In total, 105,612 unigenes were assigned for Gene Ontology (GO) terms, information for 16,730 classified unigenes was obtained in the Clusters of Orthologous Groups (COGs) database, and 13,024 unigenes matched with 224 predicted pathways in the Kyoto Encyclopedia of Genes and Genome (KEGG). In addition, genes related to putative insecticide resistance-related genes, RNAi, the Bt receptor, intestinal digestive enzymes, possible future insect control targets and immune-related molecules are described. This study provides valuable basic information that can be used as a gateway to develop new molecular tools for Monochamus alternatus Hope control strategies. PMID:26815657

  5. Toward Relatively General and Accurate Quantum Chemical Predictions of Solid-State 17O NMR Chemical Shifts in Various Biologically Relevant Oxygen-containing Compounds

    PubMed Central

    Rorick, Amber; Michael, Matthew A.; Yang, Liu; Zhang, Yong

    2015-01-01

    Oxygen is an important element in most biologically significant molecules and experimental solid-state 17O NMR studies have provided numerous useful structural probes to study these systems. However, computational predictions of solid-state 17O NMR chemical shift tensor properties are still challenging in many cases and in particular each of the prior computational work is basically limited to one type of oxygen-containing systems. This work provides the first systematic study of the effects of geometry refinement, method and basis sets for metal and non-metal elements in both geometry optimization and NMR property calculations of some biologically relevant oxygen-containing compounds with a good variety of XO bonding groups, X= H, C, N, P, and metal. The experimental range studied is of 1455 ppm, a major part of the reported 17O NMR chemical shifts in organic and organometallic compounds. A number of computational factors towards relatively general and accurate predictions of 17O NMR chemical shifts were studied to provide helpful and detailed suggestions for future work. For the studied various kinds of oxygen-containing compounds, the best computational approach results in a theory-versus-experiment correlation coefficient R2 of 0.9880 and mean absolute deviation of 13 ppm (1.9% of the experimental range) for isotropic NMR shifts and R2 of 0.9926 for all shift tensor properties. These results shall facilitate future computational studies of 17O NMR chemical shifts in many biologically relevant systems, and the high accuracy may also help refinement and determination of active-site structures of some oxygen-containing substrate bound proteins. PMID:26274812

  6. Detailed characterization of mechanical properties and molecular mobility within dry seed glasses: relevance to the physiology of dry biological systems.

    PubMed

    Ballesteros, Daniel; Walters, Christina

    2011-11-01

    Slow movement of molecules in glassy matrices controls the kinetics of chemical and physical reactions in dry seeds. Variation in physiological activity among seeds suggests that there are differences in mobility among seed glasses. Testing this hypothesis is difficult because few tools are available to measure molecular mobility within dry seeds. Here, motional properties within dry pea cotyledons were assessed using dynamic mechanical analysis. The technique detected several molecular relaxations between -80 and +80°C and gave a more detailed description of water content-temperature effects on molecular motion than previously understood from studies of glass formation in seeds at glass transition (Tg). Diffusive movement is delimited by the α relaxation, which appears to be analogous to Tg. β and γ relaxations were also detected at temperatures lower than α relaxations, clearly demonstrating intramolecular motion within the glassy matrix of the pea cotyledon. Glass transitions, or the mechanical counterpart α relaxation, appear to be less relevant to seed aging during dry storage than previously thought. On the other hand, β relaxation occurs at temperature and moisture conditions typically used for seed storage and has established importance for physical aging of synthetic polymer glasses. Our data show that the nature and extent of molecular motion varies considerably with moisture and temperature, and that the hydrated conditions used for accelerated aging experiments and ultra-dry conditions sometimes recommended for seed storage give greater molecular mobility than more standard seed storage practices. We believe characterization of molecular mobility is critical for evaluating how dry seeds respond to the environment and persist through time. PMID:21831210

  7. Biological Networks for Predicting Chemical Hepatocarcinogenicity Using Gene Expression Data from Treated Mice and Relevance across Human and Rat Species

    PubMed Central

    Thomas, Reuben; Thomas, Russell S.; Auerbach, Scott S.; Portier, Christopher J.

    2013-01-01

    Background Several groups have employed genomic data from subchronic chemical toxicity studies in rodents (90 days) to derive gene-centric predictors of chronic toxicity and carcinogenicity. Genes are annotated to belong to biological processes or molecular pathways that are mechanistically well understood and are described in public databases. Objectives To develop a molecular pathway-based prediction model of long term hepatocarcinogenicity using 90-day gene expression data and to evaluate the performance of this model with respect to both intra-species, dose-dependent and cross-species predictions. Methods Genome-wide hepatic mRNA expression was retrospectively measured in B6C3F1 mice following subchronic exposure to twenty-six (26) chemicals (10 were positive, 2 equivocal and 14 negative for liver tumors) previously studied by the US National Toxicology Program. Using these data, a pathway-based predictor model for long-term liver cancer risk was derived using random forests. The prediction model was independently validated on test sets associated with liver cancer risk obtained from mice, rats and humans. Results Using 5-fold cross validation, the developed prediction model had reasonable predictive performance with the area under receiver-operator curve (AUC) equal to 0.66. The developed prediction model was then used to extrapolate the results to data associated with rat and human liver cancer. The extrapolated model worked well for both extrapolated species (AUC value of 0.74 for rats and 0.91 for humans). The prediction models implied a balanced interplay between all pathway responses leading to carcinogenicity predictions. Conclusions Pathway-based prediction models estimated from sub-chronic data hold promise for predicting long-term carcinogenicity and also for its ability to extrapolate results across multiple species. PMID:23737943

  8. Intra-specific variability and biological relevance of P3N-PIPO protein length in potyviruses

    PubMed Central

    2013-01-01

    Background Pipo was recently described as a new ORF encoded within the genome of the Potyviridae family members (PNAS 105:5897–5902, 2008). It is embedded within the P3 cistron and is translated in the +2 reading frame relative to the potyviral long ORF as the P3N-PIPO fusion protein. In this work, we first collected pipo nucleotide sequences available for different isolates of 48 Potyvirus species. Second, to determine the biological implications of variation in pipo length, we measured infectivity, viral accumulation, cell-to-cell and systemic movements for two Turnip mosaic virus (TuMV) variants with pipo alleles of different length in three different susceptible host species, and tested for differences between the two variants. Results In addition to inter-specific variation, there was high variation in the length of the PIPO protein among isolates within species (ranging from 1 to 89 amino acids). Furthermore, selection analyses on the P3 cistron did not account for the existence of stop codons in the pipo ORF, but showed that positive selection was significant in the overlapping region for Potato virus Y (PVY) and TuMV. In some cases, variability in length was associated with host species, geographic provenance and/or other strain features. We found significant empirical differences among the phenotypes associated with TuMV pipo alleles, though the magnitude and sign of the effects were host-dependent. Conclusions The combination of computational molecular evolution analyses and experiments stemming from these analyses provide clues about the selective pressures acting upon the different-length pipo alleles and show that variation in length may be maintained by host-driven selection. PMID:24225158

  9. A multicomponent bioactive tissue-engineered blood vessel: Fabrication, mechanical evaluation and biological evaluation with physiological-relevant conditions

    NASA Astrophysics Data System (ADS)

    Bonani, Walter

    The high long-term failure rate of synthetic vascular grafts in the replacement of small vessels is known to be associated with the lack of physiological signals to vascular cells causing adverse hemodynamic, inflammatory or coagulatory events. Current studies focus on developing engineered vascular devices with ability of directing cell activity in vitro and in vivo for tissue regeneration. It is also known that controlled molecule release from scaffolds can dramatically increase the scaffold ability of directing cell activities in vitro and in vivo for tissue regeneration. To address the mechanical and biological problems associated with graft materials, we demonstrated a degradable polyester-fibroin composite tubular scaffolds which shows well-integrated nanofibrous structure, endothelial-conducive surface and anisotropic mechanical property, suitable as engineered vascular constructs. Tissue regeneration needs not only functional biomolecules providing signaling cues to cells and guide tissue remodeling, but also an adequate modality of molecule delivery. In fact, healthy tissue formation requires specific signals at well-defined place and time. To develop scaffolds with multi-modal presentation of biomolecules, we patterned electrospun nanofibers over the thickness of the 3-dimensional scaffolds by programming the deposition of interpenetrating networks of degradable polymers poly(a-caprolactone) and poly(lactide-co-glycolide) acid in tailored proportion. Fluorescent model molecules, drug and growth factors were embedded in the polymeric fibers with different techniques and release profiles were obtained and discussed. Fabrication process resulted in precise gradient patterns of materials and functional biomolecules throughout the thickness of the scaffold. These graded materials showed programmable spatio-temporal control over the release. Molecule release profiles on each side of the scaffolds were used to determine the separation efficiency of molecule

  10. Synthesis of fluorophore encapsulated silica nanoparticles for the evaluation of the biological fate and toxicity of food relevant nanoparticles

    NASA Astrophysics Data System (ADS)

    Zane, Andrew Paul

    fluorophores, rhodamine 6G and rhodamine 800, into silica shells for direct monitoring in intestinal epithelial cells and tissues of exposed mice. We show that, for small nanoparticles, a typical Stober-type ammonia driven synthesis does not yield stable fluorescence. This has been observed in literature and is attributed to incompletely hydrolyzed silica precursor causing partial dissolution of the silica shell. We remedy this by applying an arginine driven silica shell synthesis, which is known to produce a denser and more stable product at smaller particle sizes. We show that all three fluorophores can be coated in a simple generalized procedure, and the resulting particles all show stable fluorescence with no evidence of dye leakage. Using these particles, we demonstrate that silica nanoparticles can be observed internalizing into C2BBe1 intestinal epithelial cells, and in the tissues of mice that were fed the particles by gavage. We find direct evidence that the particles are absorbed into circulation and subsequently localize in organs throughout the body. Future efforts will attempt to better quantify this accumulation, as well as generalize the procedure to other food relevant nanoparticles such as TiO2.

  11. Insight into the Local Solvent Environment of Biologically Relevant Iron-nitroysl Systems through Two-Dimensional Infrared Spectroscopy

    NASA Astrophysics Data System (ADS)

    Brookes, Jennifer Faith

    Iron-nitrosyl systems, particularly in the form of heme proteins, with their iron metal active sites play an important role in biological systems. Heme proteins act as storage, transporters, and receptors for nitric oxide (NO), a signaling molecule that is important in immune, nervous, and cardiovascular systems of mammals. By better understanding the local environment of the active site of NO binding heme proteins we can gain insight into disease in which the NO pathways have been implicated. This is an important step to being able to develop pharmaceuticals targeting NO pathways in humans. Sodium nitroprusside ((SNP, Na2[Fe(CN)5is NO]·2H 2O) investigated as a model system for the active site of nitric oxide binding heme proteins. Using two-dimensional infrared spectroscopy (2D IR) to obtain dephasing dynamics of the nitrosyl stretch (nuNO) in a series of solvents we are able to better understand the local environment of the more complicated metalloproteins. Rigorous line shape analysis is performed by using nonlinear response theory to simulate 2D IR spectra which are then fit to experimental data in an iterative process to extract frequency-frequency correlation functions (FFCFs). The time scales obtained are then correlated to empirical solvent polarity parameters. The analysis of the 2D IR lineshapes reveal that the spectral diffusion timescale of the nuNO in SNP varies from 0.8 -- 4 ps and is negatively correlated with the empirical solvent polarity scales. We continue to investigate NO binding of metalloproteins through 2D IR experiments on nitrophorin 4 (NP4). NP4 is a pH-sensitive NO transporter protein present in the salivary gland of the blood sucking insect Rhodius prolixus which undergoes a pH sensitive structural change between a closed and open conformation allowing for the storage and delivery of NO. The two structures are observed spectroscopically as two distinct pH-dependent nu NO frequencies at ~1904 and ~1917 cm-1. We obtain FFCFs by globally

  12. Chemometric analysis of correlations between electronic absorption characteristics and structural and/or physicochemical parameters for ampholytic substances of biological and pharmaceutical relevance

    NASA Astrophysics Data System (ADS)

    Judycka-Proma, U.; Bober, L.; Gajewicz, A.; Puzyn, T.; Błażejowski, J.

    2015-03-01

    Forty ampholytic compounds of biological and pharmaceutical relevance were subjected to chemometric analysis based on unsupervised and supervised learning algorithms. This enabled relations to be found between empirical spectral characteristics derived from electronic absorption data and structural and physicochemical parameters predicted by quantum chemistry methods or phenomenological relationships based on additivity rules. It was found that the energies of long wavelength absorption bands are correlated through multiparametric linear relationships with parameters reflecting the bulkiness features of the absorbing molecules as well as their nucleophilicity and electrophilicity. These dependences enable the quantitative analysis of spectral features of the compounds, as well as a comparison of their similarities and certain pharmaceutical and biological features. Three QSPR models to predict the energies of long-wavelength absorption in buffers with pH = 2.5 and pH = 7.0, as well as in methanol, were developed and validated in this study. These models can be further used to predict the long-wavelength absorption energies of untested substances (if they are structurally similar to the training compounds).

  13. Development of metal based thermal barrier coatings

    NASA Astrophysics Data System (ADS)

    Shin, Dong-Il

    In this work, metal-based thermal barrier coatings (MBTBCs) have been produced, using high frequency induction plasma spraying (IPS) of iron-based nanostructured alloy powders. Important advances have been made over recent years to the development of ceramic-based thermal barrier coatings (TBCs) for internal combustion engines application, but they are not yet applied in mass production situations. Besides the important economic considerations, the reliability of ceramic: TBCs is also an issue, being associated with the difficulty of predicting their "in-service" lifetime. Through engineering of the nano/amorphous structure of MBTBCs, their thermal conductivity can be made as low as those of ceramic-based TBCs, with reduced mean free paths of the electrons/phonons scattering. In this work, nano/amorphous structured coatings were deposited by IPS using the following spray parameters: spraying distance (210 ˜ 270 mm), plasma gas composition (Ar/N2), IPS torch power (24kW), and powder feed-rate (16g/min.). The structure and properties of the deposited layers were characterized through SEM (Scanning Electron Microscopy) observations. The thermal diffusivity (alpha) properties of the MBTBCs were measured using a laser flash method. Density (rho) and specific heat (Cp) of the MBTBCs were also measured, and their thermal conductivity (k) calculated (k =alpharhoCp). The thermal conductivity of MBTBCs was found to be as low as 1.99 W/m/K. The heat treatment study showed that crystal structure changes, and grain size growth from a few nanometers to tenth of nanometers occurred at 550°C under static exposure conditions. Thermal expansion coefficient (TEC) of MBTBCs was 13E-6/K, which is close to the TEC of cast iron and thus, closer to the TEC values of aluminium alloys than are conventional TBCs. Fracture toughness of MBTBCs has also been assessed by use of Vickers hardness tests, with a 500 g load for 15 s, and the results show that there are no measurable crack

  14. Making Biology Relevant to Undergraduates

    ERIC Educational Resources Information Center

    Musante, Susan

    2012-01-01

    This article features Science Education for New Civic Engagements and Responsibilities (SENCER; www.sencer.net) Summer Institute. The SENCER program, which began formally in 2001, was the vision of David Burns; Karen Oates, currently Peterson Family Dean of Arts and Sciences at Worcester Polytechnic Institute; and Ric Wiebl, currently director of…

  15. Uptake and biological effects of environmentally relevant concentrations of the nonsteroidal anti-inflammatory pharmaceutical diclofenac in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Mehinto, Alvine C; Hill, Elizabeth M; Tyler, Charles R

    2010-03-15

    Diclofenac, a nonsteroidal anti-inflammatory drug, is widely detected in surface waters and can potentially cause deleterious effects in fish. Here, we investigated the biological effects of 21-day exposure to waterborne diclofenac at environmentally relevant concentrations (0, 0.5, 1, 5, and 25 μg/L) in rainbow trout Accumulation of diclofenac in the bile was measured and responses in selected tissues were assessed via changes in the expression of selected genes (cytochrome P450 (cyp) 1a1, cyclooxygenase (cox) 1 and 2, and p53) involved in metabolism of xenobiotics, prostaglandin synthesis, and cell cycle control, respectively, together with histopathological alterations in these tissues. Diclofenac accumulated in the bile by a factor of between 509 ± 27 and 657 ± 25 and various metabolites were putatively identified as hydroxydiclofenac, diclofenac methyl ester, and the potentially reactive metabolite hydroxydiclofenac glucuronide. Expression levels of both cox1 and cox2 in liver, gills, and kidney were significantly reduced by diclofenac exposure from only 1 μg/L. Expression of cyp1a1 was induced in the liver and the gills but inhibited in the kidney of exposed fish. Diclofenac exposure induced tubular necrosis in the kidney and hyperplasia and fusion of the villi in the intestine from 1 μg/L. This study demonstrates that subchronic exposure to environmental concentrations of diclofenac can interfere with the biochemical functions of fish and lead to tissue damage, highlighting further the concern about this pharmaceutical in the aquatic environment. PMID:20175546

  16. geneCommittee: a web-based tool for extensively testing the discriminatory power of biologically relevant gene sets in microarray data classification

    PubMed Central

    2014-01-01

    Background The diagnosis and prognosis of several diseases can be shortened through the use of different large-scale genome experiments. In this context, microarrays can generate expression data for a huge set of genes. However, to obtain solid statistical evidence from the resulting data, it is necessary to train and to validate many classification techniques in order to find the best discriminative method. This is a time-consuming process that normally depends on intricate statistical tools. Results geneCommittee is a web-based interactive tool for routinely evaluating the discriminative classification power of custom hypothesis in the form of biologically relevant gene sets. While the user can work with different gene set collections and several microarray data files to configure specific classification experiments, the tool is able to run several tests in parallel. Provided with a straightforward and intuitive interface, geneCommittee is able to render valuable information for diagnostic analyses and clinical management decisions based on systematically evaluating custom hypothesis over different data sets using complementary classifiers, a key aspect in clinical research. Conclusions geneCommittee allows the enrichment of microarrays raw data with gene functional annotations, producing integrated datasets that simplify the construction of better discriminative hypothesis, and allows the creation of a set of complementary classifiers. The trained committees can then be used for clinical research and diagnosis. Full documentation including common use cases and guided analysis workflows is freely available at http://sing.ei.uvigo.es/GC/. PMID:24475928

  17. A handy liquid metal based electroosmotic flow pump.

    PubMed

    Gao, Meng; Gui, Lin

    2014-06-01

    A room temperature liquid metal based electroosmotic flow (EOF) pump has been proposed in this work. This low-cost EOF pump is convenient for both fabrication and integration. It utilizes polydimethylsiloxane (PDMS) microchannels filled with the liquid-metal as non-contact pump electrodes. The electrode channels are fabricated symmetrically to both sides of the pumping channel, having no contact with the pumping channel. To test the pumping performance of the EOF pump, the mean flow velocities of the fluid (DI water) in the EOF pumps were experimentally measured by tracing the fluorescent microparticles in the flow. To provide guidance for designing a low voltage EOF pump, parametric studies on dimensions of the electrode and pumping channels were performed in this work. According to the experimental results, the pumping speed can reach 5.93 μm s(-1) at a driving voltage of only 1.6 V, when the gap between the electrode and the pumping channel is 20 μm. Injecting a room temperature liquid metal into microchannels can provide a simple, rapid, low-cost but accurately self-aligned way to fabricate microelectrodes for EOF pumps, which is a promising method to achieve the miniaturization and integration of the EOF pump in microfluidic systems. The non-contact liquid electrodes have no influence on the fluid in the pumping channel when pumping, reducing Joule heat generation and preventing gas bubble formation at the surface of electrodes. The pump has great potential to drive a wide range of fluids, such as drug reagents, cell suspensions and biological macromolecule solutions. PMID:24706096

  18. Engineered metal based nanoparticles and innate immunity.

    PubMed

    Petrarca, Claudia; Clemente, Emanuela; Amato, Valentina; Pedata, Paola; Sabbioni, Enrico; Bernardini, Giovanni; Iavicoli, Ivo; Cortese, Sara; Niu, Qiao; Otsuki, Takemi; Paganelli, Roberto; Di Gioacchino, Mario

    2015-01-01

    Almost all people in developed countries are exposed to metal nanoparticles (MeNPs) that are used in a large number of applications including medical (for diagnostic and therapeutic purposes). Once inside the body, absorbed by inhalation, contact, ingestion and injection, MeNPs can translocate to tissues and, as any foreign substance, are likely to encounter the innate immunity system that represent a non-specific first line of defense against potential threats to the host. In this review, we will discuss the possible effects of MeNPs on various components of the innate immunity (both specific cells and barriers). Most important is that there are no reports of immune diseases induced by MeNPs exposure: we are operating in a safe area. However, in vitro assays show that MeNPs have some effects on innate immunity, the main being toxicity (both cyto- and genotoxicity) and interference with the activity of various cells through modification of membrane receptors, gene expression and cytokine production. Such effects can have both negative and positive relevant impacts on humans. On the one hand, people exposed to high levels of MeNPs, as workers of industries producing or applying MeNPs, should be monitored for possible health effects. On the other hand, understanding the modality of the effects on immune responses is essential to develop medical applications for MeNPs. Indeed, those MeNPs that are able to stimulate immune cells could be used to develop of new vaccines, promote immunity against tumors and suppress autoimmunity. PMID:26180517

  19. Discovery of Anti-inflammatory Ingredients in Chinese Herbal Formula Kouyanqing Granule based on Relevance Analysis between Chemical Characters and Biological Effects

    PubMed Central

    Liu, Hong; Zheng, Yan-fang; Li, Chu-yuan; Zheng, Yu-ying; Wang, De-qin; Wu, Zhong; Huang, Lin; Wang, Yong-gang; Li, Pei-bo; Peng, Wei; Su, Wei-wei

    2015-01-01

    Kouyanqing Granule (KYQG) is a traditional Chinese herbal formula composed of Flos lonicerae (FL), Radix scrophulariae (RS), Radix ophiopogonis (RO), Radix asparagi (RA), and Radix et rhizoma glycyrrhizae (RG). In contrast with the typical method of separating and then biologicalily testing the components individually, this study was designed to establish an approach in order to define the core bioactive ingredients of the anti-inflammatory effects of KYQG based on the relevance analysis between chemical characters and biological effects. Eleven KYQG samples with different ingredients were prepared by changing the ratios of the 5 herbs. Thirty-eight ingredients in KYQG were identified using Ultra-fast liquid chromatography-Diode array detector-Quadrupole-Time-of-flight-Tandem mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) technology. Human oral keratinocytes (HOK) were cultured for 24 hours with 5% of Cigarette smoke extract (CSE) to induce inflammation stress. Interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-α (TNF-α) were evaluated after treatment with the eleven KYQG samples. Grey relational analysis(GRA), Pearson’s correlations (PCC), and partial least-squares (PLS) were utilized to evaluate the contribution of each ingredient. The results indicated that KYQG significantly reduced interleukin-1β, interleukin-6, interleukin-8, and tumour necrosis factor-α levels, in which lysine, γ-aminobutyric acid, chelidonic acid, tyrosine, harpagide, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isoquercitrin, luteolin-7-o-glucoside, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, angoroside C, harpagoside, cinnamic acid, and ruscogenin play a vital role. PMID:26657159

  20. Concentrative nucleoside transporter 1 (hCNT1) promotes phenotypic changes relevant to tumor biology in a translocation-independent manner

    PubMed Central

    Pérez-Torras, S; Vidal-Pla, A; Cano-Soldado, P; Huber-Ruano, I; Mazo, A; Pastor-Anglada, M

    2013-01-01

    Nucleoside transporters (NTs) mediate the uptake of nucleosides and nucleobases across the plasma membrane, mostly for salvage purposes. The canonical NTs belong to two gene families, SLC29 and SLC28. The former encode equilibrative nucleoside transporter proteins (ENTs), which mediate the facilitative diffusion of natural nucleosides with broad selectivity, whereas the latter encode concentrative nucleoside transporters (CNTs), which are sodium-coupled and show high affinity for substrates with variable selectivity. These proteins are expressed in most cell types, exhibiting apparent functional redundancy. This might indicate that CNTs have specific roles in the physiology of the cell beyond nucleoside salvage. Here, we addressed this possibility using adenoviral vectors to restore tumor cell expression of hCNT1 or a polymorphic variant (hCNT1S546P) lacking nucleoside translocation ability. We found that hCNT1 restoration in pancreatic cancer cells significantly altered cell-cycle progression and phosphorylation status of key signal-transducing kinases, promoted poly-(ADP-ribose) polymerase hyperactivation and cell death and reduced cell migration. Importantly, the translocation-defective transporter triggered these same effects on cell physiology. Moreover, this study also shows that restoration of hCNT1 expression is able to reduce tumor growth in a mouse model of pancreatic adenocarcinoma. These data predict a novel role for a NT protein, hCNT1, which appears to be independent of its role as mediator of nucleoside uptake by cells. Thereby, hCNT1 fits the profile of a transceptor in a substrate translocation-independent manner and is likely to be relevant to tumor biology. PMID:23722537

  1. Discovery of Anti-inflammatory Ingredients in Chinese Herbal Formula Kouyanqing Granule based on Relevance Analysis between Chemical Characters and Biological Effects.

    PubMed

    Liu, Hong; Zheng, Yan-fang; Li, Chu-yuan; Zheng, Yu-ying; Wang, De-qin; Wu, Zhong; Huang, Lin; Wang, Yong-gang; Li, Pei-bo; Peng, Wei; Su, Wei-wei

    2015-01-01

    Kouyanqing Granule (KYQG) is a traditional Chinese herbal formula composed of Flos lonicerae (FL), Radix scrophulariae (RS), Radix ophiopogonis (RO), Radix asparagi (RA), and Radix et rhizoma glycyrrhizae (RG). In contrast with the typical method of separating and then biologicalily testing the components individually, this study was designed to establish an approach in order to define the core bioactive ingredients of the anti-inflammatory effects of KYQG based on the relevance analysis between chemical characters and biological effects. Eleven KYQG samples with different ingredients were prepared by changing the ratios of the 5 herbs. Thirty-eight ingredients in KYQG were identified using Ultra-fast liquid chromatography-Diode array detector-Quadrupole-Time-of-flight-Tandem mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) technology. Human oral keratinocytes (HOK) were cultured for 24 hours with 5% of Cigarette smoke extract (CSE) to induce inflammation stress. Interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-α (TNF-α) were evaluated after treatment with the eleven KYQG samples. Grey relational analysis(GRA), Pearson's correlations (PCC), and partial least-squares (PLS) were utilized to evaluate the contribution of each ingredient. The results indicated that KYQG significantly reduced interleukin-1β, interleukin-6, interleukin-8, and tumour necrosis factor-α levels, in which lysine, γ-aminobutyric acid, chelidonic acid, tyrosine, harpagide, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isoquercitrin, luteolin-7-o-glucoside, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, angoroside C, harpagoside, cinnamic acid, and ruscogenin play a vital role. PMID:26657159

  2. Accessing a Biologically Relevant Benzofuran Skeleton by a One-Pot Tandem Heck Alkynylation/Cyclization Reaction Using Well-Defined Palladium N-Heterocyclic Carbene Complexes.

    PubMed

    Kumar, Anuj; Gangwar, Manoj Kumar; Prakasham, A P; Mhatre, Darshan; Kalita, Alok Ch; Ghosh, Prasenjit

    2016-03-21

    Well-defined palladium N-heterocyclic carbene (NHC) complexes were employed in the one-pot tandem Heck alkynylation/cyclization sequence for preparing biologically relevant benzofuran compounds under copper-free conditions in a time-efficient step-reduced fashion. In particular, a series of binuclear palladium complexes, 1b-1e and 2b-2e, of the alkyl-bridged NHC ligands, namely, {1,1'-di-R1-4,4'-R2-di-1,2,4-triazoline-5,5'-diylid-2-ene] (R1 = i-Pr; R2 = -(CH2)2-, -(CH2)3-), and their mononuclear analogues, trans-(NHC)PdBr2(pyridine) (3b) and cis-(NHC)PdBr2(PPh3) (3c), successfully catalyzed the one-pot tandem Heck alkynylation/cyclization reaction of 2-iodophenol with a variety of terminal alkyne substrates, yielding 2-substituted benzofuran derivatives. The mononuclear complexes 3b and 3c were nearly half as active as the representative dinuclear analogue 1c under analogous reaction conditions, thereby implying that, at the same mole percent of the palladium loading, the monometallic 3b and 3c and the bimetallic 1c complexes were equally effective as catalysts. The two sites of the bimetallic complex 1c performed as two separate independent catalytic sites, displaying no cooperativity effect in the catalysis. Finally, the practical utility of the aforementioned catalysts was demonstrated for a representative catalyst 1c through the convenient synthesis of a key intermediate, 3-[2-(benzo[d][1,3]dioxol-5-yl)-7-methoxybenzofuran-5-yl]propan-1-ol, in a total-synthesis protocol of the natural product Egonol. PMID:26928799

  3. Relevancy 101

    NASA Technical Reports Server (NTRS)

    Lynnes, Chris; Newman, Doug

    2016-01-01

    Where we present an overview on why relevancy is a problem, how important it is and how we can improve it. The topic of relevancy is becoming increasingly important in earth data discovery as our audience is tuned to the accuracy of standard search engines like Google.

  4. Bioinspired nanoreactors for the biomineralisation of metallic-based nanoparticles for nanomedicine.

    PubMed

    Bain, Jennifer; Staniland, Sarah S

    2015-06-28

    This review explores the synthesis of inorganic metallic-based nanoparticles (MBNPs) (metals, alloys, metal oxides) using biological and biologically inspired nanoreactors for precipitation/crystallisation. Such nanoparticles exhibit a range of nanoscale properties such as surface plasmon resonance (nobel metals e.g. Au), fluorescence (semiconductor quantum dots e.g. CdSe) and nanomagnetism (magnetic alloys e.g. CoPt and iron oxides e.g. magnetite), which are currently the subject of intensive research for their applicability in diagnostic and therapeutic nanomedicine. For such applications, MBNPs are required to be biocompatible, of a precise size and shape for a consistent signal or output and be easily modified with biomolecules for applications. Ideally the MBNPs would be obtained via an environmentally-friendly synthetic route. A biological or biologically inspired nanoreactor synthesis of MBNPs is shown to address these issues. Biological nanoreactors for crystallizing MBNPs within cells (magnetosomes), protein cages (ferritin) and virus capsids (cowpea chlorotic mottle, cowpea mosaic and tobacco mosaic viruses), are discussed along with how these have been modified for applications and for the next generation of new materials. Biomimetic liposome, polymersome and even designed self-assembled proteinosome nanoreactors are also reviewed for MBNP crystallisation and further modification for applications. With the advent of synthetic biology, the research and understanding in this field is growing, with the goal of realising nanoreactor synthesis of MBNPs for biomedical applications within our grasp in the near future. PMID:25865599

  5. Designing and engineering metal-based nanocomposites for nanotechnological applications

    NASA Astrophysics Data System (ADS)

    Bryan, William W.

    Metal-based nanocomposites are extremely versatile materials that can be fabricated to produce various desired responses (e.g. magnetic, optical, catalytic, mechanical, electric, and thermal). Because of their large surface-to-volume ratio, metal-based nanocomposites are unique materials that yield properties significantly different from those of bulk materials. Our research focuses on the design, synthesis, and characterization of metal-based nanocomposites utilizing various self-assembly and wet-chemical techniques. To this end, we have established several different synthetic methods for preparing metal-based nanocomposites. These metal-based nanocomposites are ideally suited for future nanotechnological applications. We report the preparation of small THPC silver, platinum, and palladium nanoparticles with diameters typically ≤ 4 nm using simple wet-chemical methods that employed THPC as the reducing agent. The dimensions of the metal nanoparticles were varied systematically by adjusting the concentration of the reactants. The THPC moieties were bound loosely to the surface of the nanoparticles and could be readily removed by centrifugation/washing. The availability of the THPC-metal nanoparticles, allowed the reliable preparation of silver, platinum, and palladium metal nanoshells. The use of a seeded-growth method facilitates the growth of pure metal nanoshells. The facile methods carried out describing nanoshell preparation, as well as the nanoshells themselves will likely supplement or replace existing nanoshells and methods of nanoshell fabrication. We extended these methodologies by demonstrating the reliable preparation of gold-coated magnetic nanoparticles using molecular self-assembly and colloidal growth chemistry. The methods described enable the reliable synthesis of core-shell nanoparticles having dimensions of ˜200 nm in total diameter. Furthermore, we demonstrated that these gold-coated magnetic nanoparticles can be coated with thin hydrogel

  6. Density functional theory estimation of isotope fractionation of Fe, Ni, Cu, and Zn among species relevant to geochemical and biological environments

    NASA Astrophysics Data System (ADS)

    Fujii, Toshiyuki; Moynier, Frédéric; Blichert-Toft, Janne; Albarède, Francis

    2014-09-01

    This paper reports the values of reduced partition function ratios (as 1000 ln β) for Fe, Ni, Cu, and Zn bound to a number of inorganic and organic ligands. We used Density Functional Techniques to update the existing data and calculate ln β for new ligands. This work allows for the mass-dependent isotope fractionation to be predicted for various inorganic (hydrated cation, hydroxide, chloride, sulfate, sulfide, phosphate) and organic (citrate, amino acid) complexes of Fe, Ni, Cu, and Zn. Isotope fractionation among coexisting complexes of these metals was evaluated from the ln β values in a variety of geochemical and biological environments. The results provide a framework for interpretation of isotope fractionation observed in seawater and chemical sediments, in the roots and aerial parts of plants, and among the organs and body fluids of mammals.

  7. Extraction and analysis methods for the determination of pyrethroid insecticides in surface water, sediments and biological tissues at environmentally relevant concentrations.

    PubMed

    Mekebri, A; Crane, D B; Blondina, G J; Oros, D R; Rocca, J L

    2008-05-01

    The aim of this study was to develop and validate chemical methods for measuring pyrethroid insecticides at environmentally relevant concentrations in different matrices. The analytes included six synthetic pyrethroids with the highest agricultural and commercial structural uses in California: bifenthrin, cyfluthrin, cypermethrin, esfenvalerate/fenvalerate, lambda-cyhalothrin, permethrin, and their corresponding stereoisomers, which includes enantiomers, diastereomers and racemic mixtures. Fortified water samples were extracted for analysis of synthetic pyrethroids using liquid-liquid extraction, while fortified sediment and fish tissue samples were extracted using pressurized fluid extraction followed by gel permeation chromatography (GPC) to remove matrix interferences. A florisil column was used for additional cleanup and fractionation of sediment and tissue extracts. Extracts were analyzed using dual column high resolution gas chromatography with electron capture detection (GC/ECD) and confirmation was obtained with gas chromatography mass spectrometry using a quadrupole ion trap detector in MS-MS mode. Method detection limits (MDLs) have been established for water (1-3 ng/L), sediment (0.5-4 ng/g dry weight) and tissue (1-3 ng/g fresh weight). Mean percent recoveries of fortified blanks and samples ranged from 75 to 115% with relative standard deviation (RSD) values less than 20% for all target compounds. PMID:18369521

  8. Insight into the structural and biological relevance of the T/R transition of the N-terminus of the B-chain in human insulin.

    PubMed

    Kosinová, Lucie; Veverka, Václav; Novotná, Pavlína; Collinsová, Michaela; Urbanová, Marie; Moody, Nicholas R; Turkenburg, Johan P; Jiráček, Jiří; Brzozowski, Andrzej M; Žáková, Lenka

    2014-06-01

    The N-terminus of the B-chain of insulin may adopt two alternative conformations designated as the T- and R-states. Despite the recent structural insight into insulin-insulin receptor (IR) complexes, the physiological relevance of the T/R transition is still unclear. Hence, this study focused on the rational design, synthesis, and characterization of human insulin analogues structurally locked in expected R- or T-states. Sites B3, B5, and B8, capable of affecting the conformation of the N-terminus of the B-chain, were subjects of rational substitutions with amino acids with specific allowed and disallowed dihedral φ and ψ main-chain angles. α-Aminoisobutyric acid was systematically incorporated into positions B3, B5, and B8 for stabilization of the R-state, and N-methylalanine and d-proline amino acids were introduced at position B8 for stabilization of the T-state. IR affinities of the analogues were compared and correlated with their T/R transition ability and analyzed against their crystal and nuclear magnetic resonance structures. Our data revealed that (i) the T-like state is indeed important for the folding efficiency of (pro)insulin, (ii) the R-state is most probably incompatible with an active form of insulin, (iii) the R-state cannot be induced or stabilized by a single substitution at a specific site, and (iv) the B1-B8 segment is capable of folding into a variety of low-affinity T-like states. Therefore, we conclude that the active conformation of the N-terminus of the B-chain must be different from the "classical" T-state and that a substantial flexibility of the B1-B8 segment, where GlyB8 plays a key role, is a crucial prerequisite for an efficient insulin-IR interaction. PMID:24819248

  9. Insight into the Structural and Biological Relevance of the T/R Transition of the N-Terminus of the B-Chain in Human Insulin

    PubMed Central

    2014-01-01

    The N-terminus of the B-chain of insulin may adopt two alternative conformations designated as the T- and R-states. Despite the recent structural insight into insulin–insulin receptor (IR) complexes, the physiological relevance of the T/R transition is still unclear. Hence, this study focused on the rational design, synthesis, and characterization of human insulin analogues structurally locked in expected R- or T-states. Sites B3, B5, and B8, capable of affecting the conformation of the N-terminus of the B-chain, were subjects of rational substitutions with amino acids with specific allowed and disallowed dihedral φ and ψ main-chain angles. α-Aminoisobutyric acid was systematically incorporated into positions B3, B5, and B8 for stabilization of the R-state, and N-methylalanine and d-proline amino acids were introduced at position B8 for stabilization of the T-state. IR affinities of the analogues were compared and correlated with their T/R transition ability and analyzed against their crystal and nuclear magnetic resonance structures. Our data revealed that (i) the T-like state is indeed important for the folding efficiency of (pro)insulin, (ii) the R-state is most probably incompatible with an active form of insulin, (iii) the R-state cannot be induced or stabilized by a single substitution at a specific site, and (iv) the B1–B8 segment is capable of folding into a variety of low-affinity T-like states. Therefore, we conclude that the active conformation of the N-terminus of the B-chain must be different from the “classical” T-state and that a substantial flexibility of the B1–B8 segment, where GlyB8 plays a key role, is a crucial prerequisite for an efficient insulin–IR interaction. PMID:24819248

  10. Characterization of the bridged hyponitrite complex {[Fe(OEP)](2)(μ-N(2)O(2))}: reactivity of hyponitrite complexes and biological relevance.

    PubMed

    Berto, Timothy C; Xu, Nan; Lee, Se Ryeon; McNeil, Anne J; Alp, E Ercan; Zhao, Jiyong; Richter-Addo, George B; Lehnert, Nicolai

    2014-07-01

    The detoxification of nitric oxide (NO) by bacterial NO reductase (NorBC) represents a paradigm of how NO can be detoxified anaerobically in cells. In order to elucidate the mechanism of this enzyme, model complexes provide a convenient means to assess potential reaction intermediates. In particular, there have been many proposed mechanisms that invoke the formation of a hyponitrite bridge between the heme b3 and nonheme iron (FeB) centers within the NorBC active site. However, the reactivity of bridged iron hyponitrite complexes has not been investigated much in the literature. The model complex {[Fe(OEP)]2(μ-N2O2)} offers a unique opportunity to study the electronic structure and reactivity of such a hyponitrite-bridged complex. Here we report the detailed characterization of {[Fe(OEP)]2(μ-N2O2)} using a combination of IR, nuclear resonance vibrational spectroscopy, electron paramagnetic resonance, and magnetic circular dichroism spectroscopy along with SQUID magnetometry. These results show that the ground-state electronic structure of this complex is best described as having two intermediate-spin (S = (3)/2) iron centers that are weakly antiferromagnetically coupled across the N2O2(2-) bridge. The analogous complex {[Fe(PPDME)]2(μ-N2O2)} shows overall similar properties. Finally, we report the unexpected reaction of {[Fe(OEP)]2(μ-N2O2)} in the presence and absence of 1-methylimidizole to yield [Fe(OEP)(NO)]. Density functional theory calculations are used to rationalize why {[Fe(OEP)]2(μ-N2O2)} cannot be formed directly by dimerization of [Fe(OEP)(NO)] and why only the reverse reaction is observed experimentally. These results thus provide insight into the general reactivity of hyponitrite-bridged iron complexes with general relevance for the N-N bond-forming step in NorBC. PMID:24971721

  11. A paradigm shift in EPH receptor interaction: biological relevance of EPHB6 interaction with EPHA2 and EPHB2 in breast carcinoma cell lines.

    PubMed

    Fox, Brian P; Kandpal, Raj P

    2011-01-01

    EPH receptors are the largest known family of receptor tyrosine kinases characterized in humans. These proteins are involved in axon guidance, tissue organization, synaptic plasticity, vascular development and the progression of various diseases including cancer. The varied biological effects of EPH receptors are mediated in part by the expression of these proteins and their intracellular binding proteins. The ability of EPH molecules to form heterodimers within their own class has been suggested, although not exhaustively characterized. We have clarified this phenomenon by showing that EPHB6, a kinase-deficient receptor, can interact with EPHB2 in mammalian cells, and more significantly EPHB6 interacts with EPHA2. However, EPHB6 does not interact with another kinase-deficient receptor, EPHA10. The interaction between EPHB6 and EPHA2 is the first demonstration of an A-type receptor interacting with a B-type receptor. Furthermore, we correlated relative expression of EPHB6, EPHB2 and EPHA2 with non-invasive and invasive phenotypes of breast tumor cell lines. Our results indicate that tumor invasiveness-suppressing activity of EPHB6 is mediated by its ability to sequester other kinase-sufficient and oncogenic EPH receptors. These observations suggest that cellular phenotypes may, in part, be attributed to a combinatorial expression of EPH receptors and heteromeric interactions among the same class, as well as between two classes, of EPH receptors. Our results also suggest that EPHA10 may transduce signals by interacting with other kinase-sufficient receptors in a similar manner. PMID:21737611

  12. An anatomical, histopathological, and molecular biological function study of the fascias posterior to the interperitoneal colon and its associated mesocolon: their relevance to colonic surgery

    PubMed Central

    Gao, Zhidong; Ye, Yingjiang; Zhang, Weiguang; Shen, Danhua; Zhong, Yanfeng; Jiang, Kewei; Yang, Xiaodong; Yin, Mujun; Liang, Bin; Tian, Long; Wang, Shan

    2013-01-01

    The study aim was to explore the anatomy, histopathology, and molecular biological function of the fascias posterior to the interperitoneal colon and its mesocolon to provide information for improving complete mesocolic excision. To accomplish this aim, we performed intraoperative observations in 60 interperitoneal colon-cancer patients accepted for complete mesocolic excision and conducted local anatomy observations for five embalmed cadavers. An additional two embalmed child cadaver specimens were studied with large slices and paraffin sections. Ten of the 60 patients were examined with a lymph node tracer technique in vivo, while fresh specimens from these patients were assessed by histopathological examination and transwell cell migration assays in vitro. The anatomical and histopathological findings showed that the fascias posterior to the interperitoneal colon and its associated mesocolon were composed of two independent layers: the visceral and parietal fascias. These two fascias were primarily composed of collagen fibers, with the parietal fascia containing a small amount of muscle fiber. The in vivo test showed that the visceral fascia surrounded the colon and its associated mesocolon, including vessels and lymphatics, and that it had no lymphatic flow through it into the rear tissues. Moreover, the in vitro assays showed the visceral fascia was able to block tumor cell migration. Although many surgical scholars have known of the existence of fascia tissue posterior to the intraperitoneal colon, the detailed structure has been ignored and been unclear. As shown by our findings, the visceral and parietal fascias are truly formed structures that have not been previously reported. A thorough understanding of fascial structures and the function of the visceral fascia barrier in blocking tumor cells will facilitate surgeons when performing high-quality complete mesocolic excision procedures. PMID:23721400

  13. Selection of appropriate tumour data sets for Benchmark Dose Modelling (BMD) and derivation of a Margin of Exposure (MoE) for substances that are genotoxic and carcinogenic: considerations of biological relevance of tumour type, data quality and uncertainty assessment.

    PubMed

    Edler, Lutz; Hart, Andy; Greaves, Peter; Carthew, Philip; Coulet, Myriam; Boobis, Alan; Williams, Gary M; Smith, Benjamin

    2014-08-01

    This article addresses a number of concepts related to the selection and modelling of carcinogenicity data for the calculation of a Margin of Exposure. It follows up on the recommendations put forward by the International Life Sciences Institute - European branch in 2010 on the application of the Margin of Exposure (MoE) approach to substances in food that are genotoxic and carcinogenic. The aims are to provide practical guidance on the relevance of animal tumour data for human carcinogenic hazard assessment, appropriate selection of tumour data for Benchmark Dose Modelling, and approaches for dealing with the uncertainty associated with the selection of data for modelling and, consequently, the derived Point of Departure (PoD) used to calculate the MoE. Although the concepts outlined in this article are interrelated, the background expertise needed to address each topic varies. For instance, the expertise needed to make a judgement on biological relevance of a specific tumour type is clearly different to that needed to determine the statistical uncertainty around the data used for modelling a benchmark dose. As such, each topic is dealt with separately to allow those with specialised knowledge to target key areas of guidance and provide a more in-depth discussion on each subject for those new to the concept of the Margin of Exposure approach. PMID:24176677

  14. Mechanism and biological relevance of blue-light (420-453 nm)-induced nonenzymatic nitric oxide generation from photolabile nitric oxide derivates in human skin in vitro and in vivo.

    PubMed

    Opländer, Christian; Deck, Annika; Volkmar, Christine M; Kirsch, Michael; Liebmann, Jörg; Born, Matthias; van Abeelen, Frank; van Faassen, Ernst E; Kröncke, Klaus-Dietrich; Windolf, Joachim; Suschek, Christoph V

    2013-12-01

    Human skin contains photolabile nitric oxide (NO) derivates such as nitrite and S-nitrosothiols, which upon UVA radiation decompose under high-output NO formation and exert NO-specific biological responses such as increased local blood flow or reduced blood pressure. To avoid the injurious effects of UVA radiation, we here investigated the mechanism and biological relevance of blue-light (420-453 nm)-induced nonenzymatic NO generation from photolabile nitric oxide derivates in human skin in vitro and in vivo. As quantified by chemiluminescence detection (CLD), at physiological pH blue light at 420 or 453 nm induced a significant NO formation from S-nitrosoalbumin and also from aqueous nitrite solutions by a to-date not entirely identified Cu(1+)-dependent mechanism. As detected by electron paramagnetic resonance spectrometry in vitro with human skin specimens, blue light irradiation significantly increased the intradermal levels of free NO. As detected by CLD in vivo in healthy volunteers, irradiation of human skin with blue light induced a significant emanation of NO from the irradiated skin area as well as a significant translocation of NO from the skin surface into the underlying tissue. In parallel, blue light irradiation caused a rapid and significant rise in local cutaneous blood flow as detected noninvasively by using micro-light-guide spectrophotometry. Irradiation of human skin with moderate doses of blue light caused a significant increase in enzyme-independent cutaneous NO formation as well as NO-dependent local biological responses, i.e., increased blood flow. The effects were attributed to blue-light-induced release of NO from cutaneous photolabile NO derivates. Thus, in contrast to UVA, blue-light-induced NO generation might be therapeutically used in the treatment of systemic and local hemodynamic disorders that are based on impaired physiological NO production or bioavailability. PMID:24121056

  15. Iron-Clad Fibers: A Metal-Based Biological Strategy for Hard Flexible Coatings

    NASA Astrophysics Data System (ADS)

    Harrington, Matthew J.; Masic, Admir; Holten-Andersen, Niels; Waite, J. Herbert; Fratzl, Peter

    2010-04-01

    The extensible byssal threads of marine mussels are shielded from abrasion in wave-swept habitats by an outer cuticle that is largely proteinaceous and approximately fivefold harder than the thread core. Threads from several species exhibit granular cuticles containing a protein that is rich in the catecholic amino acid 3,4-dihydroxyphenylalanine (dopa) as well as inorganic ions, notably Fe3+. Granular cuticles exhibit a remarkable combination of high hardness and high extensibility. We explored byssus cuticle chemistry by means of in situ resonance Raman spectroscopy and demonstrated that the cuticle is a polymeric scaffold stabilized by catecholato-iron chelate complexes having an unusual clustered distribution. Consistent with byssal cuticle chemistry and mechanics, we present a model in which dense cross-linking in the granules provides hardness, whereas the less cross-linked matrix provides extensibility.

  16. Metal-based biologically active compounds: synthesis, characterization, DNA interaction, antibacterial, cytotoxic and SOD mimic activities.

    PubMed

    Patel, Mohan N; Patel, Chintan R; Joshi, Hardik N

    2013-02-01

    The square pyramidal copper(II) complexes of N, O- donor ligand and ciprofloxacin have been synthesized. Synthesized complexes were characterized by physicochemical parameters like elemental analysis, electronic, FT-IR and LC-MS spectra. The complexes were screened for their antimicrobial activity against Gram(+Ve), i.e. Staphylococcus aureus, Bacillus subtilis, and Gram(-Ve), i.e. Serratia marcescens, Pseudomonas aeruginosa and Escherichia coli, microorganisms in terms of minimum inhibitory concentration and colony-forming unit. To determine the binding mode of complexes with Herring Sperm DNA, absorption titration and viscosity measurement were employed. DNA cleavage activity was carried out by gel electrophoresis experiment using supercoiled form of pUC19 DNA. The complexes were tested for their superoxide dismutase mimic activity in terms of IC(50) value. Synthesized complexes were also screened for their cytotoxicity using brine shrimp lethality assay method. PMID:23306896

  17. Exploring the DNA binding mode of transition metal based biologically active compounds

    NASA Astrophysics Data System (ADS)

    Raman, N.; Sobha, S.

    2012-01-01

    Few novel 4-aminoantipyrine derived Schiff bases and their metal complexes were synthesized and characterized. Their structural features and other properties were deduced from the elemental analysis, magnetic susceptibility and molar conductivity as well as from mass, IR, UV-vis, 1H NMR and EPR spectral studies. The binding of the complexes with CT-DNA was analyzed by electronic absorption spectroscopy, viscosity measurement, and cyclic voltammetry. The interaction of the metal complexes with DNA was also studied by molecular modeling with special reference to docking. The experimental and docking results revealed that the complexes have the ability of interaction with DNA of minor groove binding mode. The intrinsic binding constants ( Kb) of the complexes with CT-DNA were found out which show that they are minor groove binders. Gel electrophoresis assay demonstrated the ability of the complexes to cleave the pUC19 DNA in the presence of AH 2 (ascorbic acid). Moreover, the oxidative cleavage studies using distamycin revealed the minor groove binding for the newly synthesized 4-aminoantipyrine derived Schiff bases and their metal complexes. Evaluation of antibacterial activity of the complexes against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis, and Klebsiella pneumoniae exhibited that the complexes have potent biocidal activity than the free ligands.

  18. Metal-based biologically active azoles and β-lactams derived from sulfa drugs.

    PubMed

    Ebrahimi, Hossein Pasha; Hadi, Jabbar S; Almayah, Abdulelah A; Bolandnazar, Zeinab; Swadi, Ali G; Ebrahimi, Amirpasha

    2016-03-01

    Metal complexes of Schiff bases derived from sulfamethoxazole (SMZ) and sulfathiazole (STZ), converted to their β-lactam derivatives have been synthesized and experimentally characterized by elemental analysis, spectral (IR, (1)H NMR, (13)C NMR, and EI-mass), molar conductance measurements and thermal analysis techniques. The structural and electronic properties of the studied molecules were investigated theoretically by performing density functional theory (DFT) to access reliable results to the experimental values. The spectral and thermal analysis reveals that the Schiff bases act as bidentate ligands via the coordination of azomethine nitrogen to metal ions as well as the proton displacement from the phenolic group through the metal ions; therefore, Cu complexes can attain the square planner arrangement and Zn complexes have a distorted tetrahedral structure. The thermogravimetric (TG/DTG) analyses confirm high stability for all complexes followed by thermal decomposition in different steps. In addition, the antibacterial activities of synthesized compounds have been screened in vitro against various pathogenic bacterial species. Inspection of the results revealed that all newly synthesized complexes individually exhibit varying degrees of inhibitory effects on the growth of the tested bacterial species, therefore, they may be considered as drug candidates for bacterial pathogens. The free Schiff base ligands (1-2) exhibited a broad spectrum antibacterial activity against Gram negative Escherichia coli, Pseudomonas aeruginosa, and Proteus spp., and Gram positive Staphylococcus aureus bacterial strains. The results also indicated that the β-lactam derivatives (3-4) have high antibacterial activities on Gram positive bacteria as well as the metal complexes (5-8), particularly Zn complexes, have a significant activity against all Gram negative bacterial strains. It has been shown that the metal complexes have significantly higher activity than corresponding ligands due to chelation process which reduces the polarity of metal ion by coordinating with ligands. PMID:26833242

  19. Metal based isatin-derived sulfonamides: their synthesis, characterization, coordination behavior and biological activity.

    PubMed

    Chohan, Zahid H; Supuran, Claudiu T; Ben Hadda, Taibi; Nasim, Faiz-Ul-Hassan; Khan, Khalid M

    2009-06-01

    Some isatin derived sulfonamides and their transition metal [Co(II), Cu(II), Ni(II), Zn(II)] complexes have been synthesized and characterized. The structure of synthesized compounds and their nature of bonding have been inferred on the basis of their physical (magnetic susceptibility and conductivity measurements), analytical (elemental analyses) and spectral (IR, (1)H NMR and (13)C NMR) properties. An octahedral geometry has been suggested for Co(II), Ni(II) and Zn(II) and square-planar for Cu(II) complexes. In order to assess the antibacterial and antifungal behavior, the ligands and their metal(II) complexes were screened for their in vitro antibacterial activity against four Gram-negative species, Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa and Salmonella typhi and two Gram-positive species, Staphylococcus aureus and Bacillus subtilis and, for in vitro antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata. In vitro cytotoxic properties of all the compounds were also studied against Artemia salina by brine shrimp bioassay. The results of average antibacterial/antifungal activity showed that zinc(II) complexes were found to be the most active against one or more bacterial/fungal strains as compared to the other metal complexes. PMID:18825557

  20. Biology and clinical relevance of granulysin

    PubMed Central

    Krensky, A. M.; Clayberger, C.

    2009-01-01

    Granulysin is a cytolytic and proinflammatory molecule first identified by a screen for genes expressed ‘late’ (3–5 days) after activation of human peripheral blood mononuclear cells. Granulysin is present in cytolytic granules of cytotoxic T lymphocytes and natural killer cells. Granulysin is made in a 15-kDa form that is cleaved into a 9-kDa form at both the amino and the carboxy termini. The 15-kDa form is constitutively secreted, and its function remains poorly understood. The 9-kDa form is released by receptor-mediated granule exocytosis. Nine kiloDalton granulysin is broadly cytolytic against tumors and microbes, including gram-positive and gram-negative bacteria, fungi/yeast and parasites. It kills the causative agents of both tuberculosis and malaria. Granulysin is also a chemoattractant for T lymphocytes, monocytes and other inflammatory cells and activates the expression of a number of cytokines, including regulated upon activation T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, MCP-3, macrophage inflammatory protein (MIP)-1α, interleukin (IL)-10, IL-1, IL-6 and interferon (IFN)-α. Granulysin is implicated in a myriad of diseases including infection, cancer, transplantation, autoimmunity, skin and reproductive maladies. Small synthetic forms of granulysin are being developed as novel antibiotics. Studies of the full-length forms may give rise to new diagnostics and therapeutics for use in a wide variety of diseases. PMID:19254247

  1. Sirtuin biology and relevance to diabetes treatment

    PubMed Central

    Dong, X Charlie

    2012-01-01

    SUMMARY Sirtuins are a group of NAD+-dependent enzymes that post-translationally modify histones and other proteins. Among seven mammalian sirtuins, SIRT1 has been the most extensively studied and has been demonstrated to play a critical role in all major metabolic organs and tissues. SIRT1 regulates glucose and lipid homeostasis in the liver, modulates insulin secretion in pancreatic islets, controls insulin sensitivity and glucose uptake in skeletal muscle, increases adiponectin expression in white adipose tissue and controls food intake and energy expenditure in the brain. Recently, SIRT3 has been demonstrated to modulate insulin sensitivity in skeletal muscle and systemic metabolism, and Sirt3-null mice manifest characteristics of metabolic syndrome on a high-fat diet. Thus, it is reasonable to believe that enhancing the activities of SIRT1 and SIRT3 may be beneficial for Type 2 diabetes. Although it is controversial, the SIRT1 activator SRT1720 has been reported to be effective in improving glucose metabolism and insulin sensitivity in animal models. More research needs to be conducted so that we can better understand the physiological functions and molecular mechanisms of sirtuins in order to therapeutically target these enzymes for diabetes treatment. PMID:23024708

  2. Mammalian Sirtuins: Biological Insights and Disease Relevance

    PubMed Central

    Haigis, Marcia C.; Sinclair, David A.

    2010-01-01

    Aging is accompanied by a decline in the healthy function of multiple organ systems, leading to increased incidence and mortality from diseases such as type II diabetes mellitus, neurodegenerative diseases, cancer, and cardiovascular disease. Historically, researchers have focused on investigating individual pathways in isolated organs as a strategy to identify the root cause of a disease, with hopes of designing better drugs. Studies of aging in yeast led to the discovery of a family of conserved enzymes known as the sirtuins, which affect multiple pathways that increase the life span and the overall health of organisms. Since the discovery of the first known mammalian sirtuin, SIRT1, 10 years ago, there have been major advances in our understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span. This review summarizes and discusses the advances of the past decade and the challenges that will confront the field in the coming years. PMID:20078221

  3. Nitric oxide. Novel biology with clinical relevance.

    PubMed Central

    Billiar, T R

    1995-01-01

    OBJECTIVE: The author provides the reader with a view of the regulation and function of nitric oxide (NO), based on the three distinct enzyme isoforms that synthesize NO. SUMMARY BACKGROUND DATA: Nitric oxide is a short-lived molecule exhibiting functions as diverse as neurotransmission and microbial killing. Recent advances in the characterization of the enzymes responsible for NO synthesis and in the understanding of how NO interacts with targets have led to new insights into the many facets of this diverse molecule. METHODS: Nitric oxide is produced by one of three enzyme isoforms of NO synthesis. These enzymes vary considerably in their distribution, regulation, and function. Accordingly, the NO synthesis or lack of NO production will have consequences unique to that isoform. Therefore, this review summarizes the regulation and function of NO generated by each of the three isoforms. RESULTS: Nitric oxide exhibits many unique characteristics that allow this molecule to perform so many functions. The amount, duration, and location of the NO synthesis will depend on the isoform of NO synthase expressed. For each isoform, there probably are disease processes in which deficiency states exist. For induced NO synthesis, states of overexpression exist. CONCLUSIONS: Understanding the regulation and function of the enzymes that produce NO and the unique characteristics of each enzyme isoform is likely to lead to therapeutic approaches to prevent or treat a number of diseases. PMID:7537035

  4. Prion biology relevant to bovine spongiform encephalopathy.

    PubMed

    Novakofski, J; Brewer, M S; Mateus-Pinilla, N; Killefer, J; McCusker, R H

    2005-06-01

    Bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD) of deer and elk are a threat to agriculture and natural resources, as well as a human health concern. Both diseases are transmissible spongiform encephalopathies (TSE), or prion diseases, caused by autocatalytic conversion of endogenously encoded prion protein (PrP) to an abnormal, neurotoxic conformation designated PrPsc. Most mammalian species are susceptible to TSE, which, despite a range of species-linked names, is caused by a single highly conserved protein, with no apparent normal function. In the simplest sense, TSE transmission can occur because PrPsc is resistant to both endogenous and environmental proteinases, although many details remain unclear. Questions about the transmission of TSE are central to practical issues such as livestock testing, access to international livestock markets, and wildlife management strategies, as well as intangible issues such as consumer confidence in the safety of the meat supply. The majority of BSE cases seem to have been transmitted by feed containing meat and bone meal from infected animals. In the United Kingdom, there was a dramatic decrease in BSE cases after neural tissue and, later, all ruminant tissues were banned from ruminant feed. However, probably because of heightened awareness and widespread testing, there is growing evidence that new variants of BSE are arising "spontaneously," suggesting ongoing surveillance will continue to find infected animals. Interspecies transmission is inefficient and depends on exposure, sequence homology, TSE donor strain, genetic polymorphism of the host, and architecture of the visceral nerves if exposure is by an oral route. Considering the low probability of interspecies transmission, the low efficiency of oral transmission, and the low prion levels in nonnervous tissues, consumption of conventional animal products represents minimal risk. However, detection of rare events is challenging, and TSE literature is characterized by subsequently unsupported claims of species barriers or absolute tissue safety. This review presents an overview of TSE and summarizes recent research on pathogenesis and transmission. PMID:15890824

  5. Formability Evaluation of Sheet Metals Based on Global Strain Distribution

    NASA Astrophysics Data System (ADS)

    Zhang, Ling; Lin, Jianping; Min, Junying; Ye, You; Kang, Liugen

    2016-04-01

    According to the conventional methods for formability evaluation, e.g., forming limit curve (FLC), limit dome height, and total elongation, inconsistent results are observed when comparing the formability of four advanced high-strength steels (AHSS) with an ultimate tensile strength grade of 1000 MPa. The strain distribution analysis with the aid of digital image correlation technique shows that different uniform deformation capabilities of sheet metals under the same loading conditions are responsible for this inconsistency. In addition, metallurgical analysis suggests that inhomogeneous microstructure distribution and phase transformation during deformation in some materials play important roles in the uniform deformation capability of sheet metal. Limit strains on the commonly used FLC only relate to the major and minor strains of local deforming elements associated with the onset of necking. However, the formability of a sheet metal component is determined by the strain magnitudes of all deforming elements involved during the forming process. Hence, the formability evaluation of sheet metals from a global aspect is more applicable for practical engineering. A new method based on two indices (i.e., which represent global formability and uniform deformation capability, respectively) is proposed to evaluate the formability of sheet metals based on global strain distribution. The formability and evolution of deformation uniformity of the investigated AHSS at different stress states are studied with this new method. Compared with other formability evaluation methods, the new method is demonstrated to be more appropriate for practical engineering, and it is applicable to both in-plane and out-of-plane deformation. Additionally, the global formability of sheet metals can be more comprehensively understood with this new method.

  6. Formability Evaluation of Sheet Metals Based on Global Strain Distribution

    NASA Astrophysics Data System (ADS)

    Zhang, Ling; Lin, Jianping; Min, Junying; Ye, You; Kang, Liugen

    2016-06-01

    According to the conventional methods for formability evaluation, e.g., forming limit curve (FLC), limit dome height, and total elongation, inconsistent results are observed when comparing the formability of four advanced high-strength steels (AHSS) with an ultimate tensile strength grade of 1000 MPa. The strain distribution analysis with the aid of digital image correlation technique shows that different uniform deformation capabilities of sheet metals under the same loading conditions are responsible for this inconsistency. In addition, metallurgical analysis suggests that inhomogeneous microstructure distribution and phase transformation during deformation in some materials play important roles in the uniform deformation capability of sheet metal. Limit strains on the commonly used FLC only relate to the major and minor strains of local deforming elements associated with the onset of necking. However, the formability of a sheet metal component is determined by the strain magnitudes of all deforming elements involved during the forming process. Hence, the formability evaluation of sheet metals from a global aspect is more applicable for practical engineering. A new method based on two indices (i.e., which represent global formability and uniform deformation capability, respectively) is proposed to evaluate the formability of sheet metals based on global strain distribution. The formability and evolution of deformation uniformity of the investigated AHSS at different stress states are studied with this new method. Compared with other formability evaluation methods, the new method is demonstrated to be more appropriate for practical engineering, and it is applicable to both in-plane and out-of-plane deformation. Additionally, the global formability of sheet metals can be more comprehensively understood with this new method.

  7. Genetic characterization of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18) with relevant biological roles in lagomorphs

    PubMed Central

    Neves, Fabiana; Abrantes, Joana; Almeida, Tereza; de Matos, Ana Lemos; Costa, Paulo P

    2015-01-01

    ILs, as essential innate immune modulators, are involved in an array of biological processes. In the European rabbit (Oryctolagus cuniculus) IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18 have been implicated in inflammatory processes and in the immune response against rabbit hemorrhagic disease virus and myxoma virus infections. In this study we characterized these ILs in six Lagomorpha species (European rabbit, pygmy rabbit, two cottontail rabbit species, European brown hare and American pika). Overall, these ILs are conserved between lagomorphs, including in their exon/intron structure. Most differences were observed between leporids and American pika. Indeed, when comparing both, some relevant differences were observed in American pika, such as the location of the stop codon in IL-1α and IL-2, the existence of a different transcript in IL8 and the number of cysteine residues in IL-1β. Changes at N-glycosylation motifs were also detected in IL-1, IL-10, IL-12B and IL-15. IL-1α is the protein that presents the highest evolutionary distances, which is in contrast to IL-12A where the distances between lagomorphs are the lowest. For all these ILs, sequences of human and European rabbit are more closely related than between human and mouse or European rabbit and mouse. PMID:26395994

  8. Genetic characterization of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18) with relevant biological roles in lagomorphs.

    PubMed

    Neves, Fabiana; Abrantes, Joana; Almeida, Tereza; de Matos, Ana Lemos; Costa, Paulo P; Esteves, Pedro J

    2015-11-01

    ILs, as essential innate immune modulators, are involved in an array of biological processes. In the European rabbit (Oryctolagus cuniculus) IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18 have been implicated in inflammatory processes and in the immune response against rabbit hemorrhagic disease virus and myxoma virus infections. In this study we characterized these ILs in six Lagomorpha species (European rabbit, pygmy rabbit, two cottontail rabbit species, European brown hare and American pika). Overall, these ILs are conserved between lagomorphs, including in their exon/intron structure. Most differences were observed between leporids and American pika. Indeed, when comparing both, some relevant differences were observed in American pika, such as the location of the stop codon in IL-1α and IL-2, the existence of a different transcript in IL8 and the number of cysteine residues in IL-1β. Changes at N-glycosylation motifs were also detected in IL-1, IL-10, IL-12B and IL-15. IL-1α is the protein that presents the highest evolutionary distances, which is in contrast to IL-12A where the distances between lagomorphs are the lowest. For all these ILs, sequences of human and European rabbit are more closely related than between human and mouse or European rabbit and mouse. PMID:26395994

  9. The X-ray Crystal Structure of the Phage Tail Terminator Protein Reveals the Biologically Relevant Hexameric Rang Structure and Demonstrates a Conserved mechanism of Tail Termination among Divrse Long Tailed Phages

    SciTech Connect

    Pell, L.; Liu, A; Edmonds, L; Donaldson, L; Howell, L; Davidson, A

    2009-01-01

    The tail terminator protein (TrP) plays an essential role in phage tail assembly by capping the rapidly polymerizing tail once it has reached its requisite length and serving as the interaction surface for phage heads. Here, we present the 2.7-A crystal structure of a hexameric ring of gpU, the TrP of phage ?. Using sequence alignment analysis and site-directed mutagenesis, we have shown that this multimeric structure is biologically relevant and we have delineated its functional surfaces. Comparison of the hexameric crystal structure with the solution structure of gpU that we previously solved using NMR spectroscopy shows large structural changes occurring upon multimerization and suggests a mechanism that allows gpU to remain monomeric at high concentrations on its own, yet polymerize readily upon contact with an assembled tail tube. The gpU hexamer displays several flexible loops that play key roles in head and tail binding, implying a role for disorder-to-order transitions in controlling assembly as has been observed with other ? morphogenetic proteins. Finally, we have found that the hexameric structure of gpU is very similar to the structure of a putative TrP from a contractile phage tail even though it displays no detectable sequence similarity. This finding coupled with further bioinformatic investigations has led us to conclude that the TrPs of non-contractile-tailed phages, such as ?, are evolutionarily related to those of contractile-tailed phages, such as P2 and Mu, and that all long-tailed phages may utilize a conserved mechanism for tail termination.

  10. Photodynamic Therapy and the Development of Metal-Based Photosensitisers

    PubMed Central

    Josefsen, Leanne B.; Boyle, Ross W.

    2008-01-01

    Photodynamic therapy (PDT) is a treatment modality that has been used in the successful treatment of a number of diseases and disorders, including age-related macular degeneration (AMD), psoriasis, and certain cancers. PDT uses a combination of a selectively localised light-sensitive drug (known as a photosensitiser) and light of an appropriate wavelength. The light-activated form of the drug reacts with molecular oxygen to produce reactive oxygen species (ROS) and radicals; in a biological environment these toxic species can interact with cellular constituents causing biochemical disruption to the cell. If the homeostasis of the cell is altered significantly then the cell enters the process of cell death. The first photosensitiser to gain regulatory approval for clinical PDT was Photofrin. Unfortunately, Photofrin has a number of associated disadvantages, particularly pro-longed patient photosensitivity. To try and overcome these disadvantages second and third generation photosensitisers have been developed and investigated. This Review highlights the key photosensitisers investigated, with particular attention paid to the metallated and non-metallated cyclic tetrapyrrolic derivatives that have been studied in vitro and in vivo; those which have entered clinical trials; and those that are currently in use in the clinic for PDT. PMID:18815617

  11. Earthdata Search: The Relevance of Relevance

    NASA Technical Reports Server (NTRS)

    Quinn, Patrick

    2016-01-01

    Through recent usability studies, the issue of relevance became increasingly clear in the Earthdata Search Client. After all, if a user can't find the data they are looking for, nothing else we do matters. This presentation walks through usability testing findings and recent relevance improvements made to the Earthdata Search Client.

  12. Ballistic Hot Electron Transport in Heteroepitaxial SrRuO3 Metal-Base Transistors

    NASA Astrophysics Data System (ADS)

    Kim, Brian; Hikita, Yasuyuki; Yajima, Takeaki; Bell, Christopher; Hwang, Harold

    Perovskite oxide heterostructures is a rapidly emerging field significant for interface-induced electronic and magnetic reconstructions, resulting in novel phases distinct from those found in the bulk counterparts. Notably, utilizing device structures is an effective way to probe these interface-induced phases. One of the most prevalent device structures that has been adopted so far is a three-terminal field-effect geometry, used to probe in-plane electronic transport properties. However, the out-of-plane three-terminal device geometry, though less studied due to its complexity, is also useful in many aspects. In the metal-base transistor (MBT), for instance, ballistic transport of hot electrons injected across a Schottky diode emitter can be used to probe hot electron properties of the metal-base, providing information on inelastic scattering mechanisms, electron confinement effects, and intervalley transfer. One promising model system for the metal-base is SrRuO3 (SRO), characterized by intermediate electron correlations with unusual transport properties. Here we present an all-perovskite oxide heteroepitaxial MBT using SRO as a metal-base layer. Successful MBT operation for various metal-base layer thicknesses was achieved, from which the hot electron attenuation length of SRO was deduced. These results form a foundation on which to examine the properties of hot electrons in strongly correlated systems using the out-of-plane three-terminal device geometry.

  13. Bivalent metal-based MIL-53 analogues: Synthesis, properties and application

    SciTech Connect

    Liu, Yongxin; Liu, Dan; Wang, Cheng

    2015-03-15

    Trivalent metal-based MIL-53 (Al{sup 3+}, Cr{sup 3+}, Fe{sup 3+}, In{sup 3+}) compounds are interesting metal–organic frameworks (MOFs) with breathing effect and are promising gas sorption materials. Replacing bridging μ{sub 2}-OH group by neutral ligands such as pyridine N-oxide and its derivatives (PNOs), the trivalent metal-based MIL-53 analogous structures could be extended to bivalent metal systems. The introduction of PNOs and bivalent metal elements endows the frameworks with new structural features and physical and chemical properties. This minireview summarizes the recent development of bivalent metal-based MIL-53 analogues (Mn{sup 2+}, Co{sup 2+}, Ni{sup 2+}), typically, focusing on the synthetic strategies and potential applications based on our own works and literatures. We present the synthetic strategy to achieve structures evolution from single-ligand-walled to double-ligand-walled channel. Properties and application of these new materials in a wide range of potential areas are discussed including thermal stability, gas adsorption, magnetism and liquid-phase separation. Promising directions of this research field are also highlighted. - Graphical abstract: The recent development of bivalent metal-based MIL-53 analogues (Mn{sup 2+}, Co{sup 2+}, Ni{sup 2+}) on their synthetic strategies, properties and potential applications was reviewed. - Highlights: • Structure features of bivalent metal-based MIL-53 analogues are illustrated. • Important properties and application are presented. • Host–guest interactions are main impetus for liquid-phase separation. • Promising directions of bivalent metal-based MIL-53 analogues are highlighted.

  14. Synthesis and property investigation of metal-based nanomaterials for biotechnological applications

    NASA Astrophysics Data System (ADS)

    Darsanasiri, Nalin Dammika

    Luminescent lanthanide-based materials have drawn recent interest due to their applications in in vitro cellular imaging. Sensitive biological analysis requires optical labels with high water dispersibility & stability and excellent luminescent properties. Most literature reported lanthanide complexes with high luminescence intensity are hydrophobic and unstable, limiting their biological applications. This project was designed to incorporate a highly luminescent lanthanide beta-diketonate complex in a silica nanoparticle. Eu(btfa)3dmph complex was synthesized, which exhibits red luminescence at 614 nm with a narrow (15 nm) full with half-maximum (btfa=4,4,4-trifluoro-1-phenyl-1,3-butanedione, dmph=4,7-dimethyl,1,10-phenanthroline). A synthetic procedure was optimized to incorporate the Eu-complex in a silica-based nanoparticle with an average particle diameter of 36 nm. Eu-complex based silica nanoparticles exhibit high stability and water-dispersibility with a luminescence quantum yield of 10 %. The nanoparticles showed antimicrobial activity against clinically important E.coli, S.aureus and S.epidermidis. Synthesis, materials characterization, and antimicrobial studies of the complex and the nanoparticles was discussed in the first part of this thesis. Nanotechnology is emerging as a new interdisciplinary field combining biology, chemistry, physics, and material science. Recent advances promise developments in the synthesis, modification and practical applications of polymer-coated manganese (Mn)-based zinc oxide (ZnO) nanoparticles (NPs). The size distribution, shape, and surface modification of metal-based ZnO nanoparticles are the key factors determining their specific physical properties. Due to the strong antibacterial properties and low toxicity towards mammalian cells, ZnO NPs have been successfully used in a wide range of applications including wound dressing, protective clothing, antibacterial surfaces, food preservation, and cosmetics as biocidal and

  15. Engineered metal based nanomaterials in aqueous environments: Interactions, transformations and implications

    NASA Astrophysics Data System (ADS)

    Mudunkotuwa, Imali Ama

    Nanoscience and nanotechnology offer potential routes towards addressing critical issues such as clean and sustainable energy, environmental protection and human health. Specifically, metal and metal oxide nanomaterials are found in a wide range of applications and therefore hold a greater potential of possible release into the environment or for the human to be exposed. Understanding the aqueous phase behavior of metal and metal oxide nanomaterials is a key factor in the safe design of these materials because their interactions with living systems are always mediated through the aqueous phase. Broadly the transformations in the aqueous phase can be classified as dissolution, aggregation and adsorption which are dependent and linked processes to one another. The complexity of these processes at the liquid-solid interface has therefore been one of the grand challenges that has persisted since the beginning of nanotechnology. Although classical models provide guidance for understanding dissolution and aggregation of nanoparticles in water, there are many uncertainties associated with the recent findings. This is often due to a lack of fundamental knowledge of the surface structure and surface energetics for very small particles. Therefore currently the environmental health and safety studies related to nanomaterials are more focused on understanding the surface chemistry that governs the overall processes in the liquid-solid interfacial region at the molecular level. The metal based nanomaterials focused on in this dissertation include TiO2, ZnO, Cu and CuO. These are among the most heavily used in a number of applications ranging from uses in the construction industry to cosmetic formulation. Therefore they are produced in large scale and have been detected in the environment. There is debate within the scientific community related to their safety as a result of the lack of understanding on the surface interactions that arise from the detailed nature of the surfaces

  16. Single Particle ICPMS for Characterizing Metal-based Nanoparticles and Monitoring Transformation Processes in Surface Water

    EPA Science Inventory

    Engineered metal-based nanomaterials will likely be used in increasing quantities in consumer and industrial products. These may be introduced into surface waters by a variety of paths depending on usage. Other naturally occurring and anthropogenic particles containing these met...

  17. Characterizing Metal-Based Nanoparticles in Surface Water by Single-Particle ICPMS

    EPA Science Inventory

    Engineered metal-based nanomaterials are being used in increasing quantities in consumer and industrial products. These materials may be introduced into surface waters by a variety of paths depending on usage, and will be superimposed on concentrations of other particles containi...

  18. SINGLE-PARTICLE ICPMS FOR CHARACTERIZING METAL-BASED NANOPARTICLES IN THE ENVIRONMENT - ADVANCES AND CHALLENGES

    EPA Science Inventory

    As engineered metal-based nanomaterials become widely used in consumer and industrial products, the amount of these materials introduced into the environment by a variety of paths will increase. The concentration of metal associated with these engineered nanoparticles will be s...

  19. The Importance of Being Relevant

    PubMed Central

    Jaswal, Snehlata

    2012-01-01

    This review aims at an understanding of the binding process by synthesizing the extant perspectives regarding binding. It begins with a consideration of the biological explanations of binding, viz., conjunctive coding, synchrony, and reentrant mechanisms. Thereafter binding is reviewed as a psychological process guided by top-down signals. The stages and types of binding proposed by various researchers are discussed in this section. The next section introduces Working Memory (WM) as the executive directing the top-down signals. After that it is described how WM works by selecting relevant sensory input, followed by a detailed consideration of the debate regarding objects vs. features with the conclusion that relevance is the key factor determining what is processed. The next section considers other factors affecting the selection of relevant input. Then, we shift focus to describe what happens to irrelevant input – whether it is discarded at the outset or is gradually inhibited, and whether inhibition is a perceptual or post-perceptual process. The concluding section describes the process of binding as currently understood on the basis of the literature included in the review. To summarize, it appears that initially the “object” is conceptualized as an instantaneous bundle of all features. However, only relevant features of stimuli are gradually integrated to form a stable representation of the object. Concomitantly, irrelevant features are removed from the object representations. Empirical evidence suggests that the inhibition of irrelevant features occurs over time and is presumably a process within WM. PMID:22969739

  20. Perceptions of document relevance

    PubMed Central

    Bruza, Peter; Chang, Vivien

    2014-01-01

    This article presents a study of how humans perceive and judge the relevance of documents. Humans are adept at making reasonably robust and quick decisions about what information is relevant to them, despite the ever increasing complexity and volume of their surrounding information environment. The literature on document relevance has identified various dimensions of relevance (e.g., topicality, novelty, etc.), however little is understood about how these dimensions may interact. We performed a crowdsourced study of how human subjects judge two relevance dimensions in relation to document snippets retrieved from an internet search engine. The order of the judgment was controlled. For those judgments exhibiting an order effect, a q–test was performed to determine whether the order effects can be explained by a quantum decision model based on incompatible decision perspectives. Some evidence of incompatibility was found which suggests incompatible decision perspectives is appropriate for explaining interacting dimensions of relevance in such instances. PMID:25071622

  1. Removal of inorganic mercury and methylmercury from surface waters following coagulation of dissolved organic matter with metal-based salts

    USGS Publications Warehouse

    Henneberry, Y.K.; Kraus, T.E.C.; Fleck, J.A.; Krabbenhoft, D.P.; Bachand, P.M.; Horwath, W.R.

    2011-01-01

    The presence of inorganic mercury (IHg) and methylmercury (MeHg) in surface waters is a health concern worldwide. This study assessed the removal potential use of metal-based coagulants as a means to remove both dissolved IHg and MeHg from natural waters and provides information regarding the importance of Hg associations with the dissolved organic matter (DOM) fraction and metal hydroxides. Previous research indicated coagulants were not effective at removing Hg from solution; however these studies used high concentrations of Hg and did not reflect naturally occurring concentrations of Hg. In this study, water collected from an agricultural drain in the Sacramento-San Joaquin Delta was filtered to isolate the dissolved organic matter (DOM) fraction. The DOM was then treated with a range of coagulant doses to determine the efficacy of removing all forms of Hg from solution. Three industrial-grade coagulants were tested: ferric chloride, ferric sulfate, and polyaluminum chloride. Coagulation removed up to 85% of DOM from solution. In the absence of DOM, all three coagulants released IHg into solution, however in the presence of DOM the coagulants removed up to 97% of IHg and 80% of MeHg. Results suggest that the removal of Hg is mediated by DOM-coagulant interactions. There was a preferential association of IHg with the more aromatic, higher molecular weight fraction of DOM but no such relationship was found for MeHg. This study offers new fundamental insights regarding large-scale removal of Hg at environmentally relevant regarding large-scale removal of Hg at environmentally relevant concentrations.

  2. Rigor, Relevance and Relationships

    ERIC Educational Resources Information Center

    McNulty, Raymond J.; Quaglia, Russell J.

    2007-01-01

    Rigor, relevance, and relationships are three elements that provide the hallmark for education today. These three elements are integrally connected; if one is missing in a teacher's teaching practices, he or she is not doing his or her best to prepare students for success in school and in life. To ensure the inclusion of both rigor and relevance,…

  3. Culturally Relevant Pedagogy

    ERIC Educational Resources Information Center

    Irvine, Jacqueline Jordan

    2010-01-01

    Many teachers have only a cursory understanding of culturally relevant pedagogy, and their efforts to bridge the cultural gap often fall short. Culturally relevant pedagogy is a term that describes effective teaching in culturally diverse classrooms. It can be a daunting idea to understand and implement. Yet people tend to appreciate culturally…

  4. Making Science Relevant

    ERIC Educational Resources Information Center

    Eick, Charles; Deutsch, Bill; Fuller, Jennifer; Scott, Fletcher

    2008-01-01

    Science teachers are always looking for ways to demonstrate the relevance of science to students. By connecting science learning to important societal issues, teachers can motivate students to both enjoy and engage in relevant science (Bennet, Lubben, and Hogarth 2007). To develop that connection, teachers can help students take an active role in…

  5. Defining a metal-based waste form for IFR pyroprocessing wastes

    SciTech Connect

    McDeavitt, S.M.; Park, J.Y.; Ackerman, J.P.

    1994-01-01

    Pyrochemical electrorefining to recover actinides from metal nuclear fuel is a key element of the Integral Fast Reactor (IFR) fuel cycle. The process separates the radioactive fission products from the long-lived actinides in a molten LiCl-KCl salt, and it generates a lower waste volume with significantly less long-term toxicity as compared to spent nuclear fuel. The process waste forms include a mineral-based waste form that will contain fission products removed from an electrolyte salt and a metal-based waste form that will contain metallic fission products and the fuel cladding and process materials. Two concepts for the metal-based waste form are being investigated: (1) encapsulating the metal constituents in a Cu-Al alloy and (2) alloying the metal constituents into a uniform stainless steel-based waste form. Results are given from our recent studies of these two concepts.

  6. Partial-surface-passivation strategy for transition-metal-based copper-gold nanocage.

    PubMed

    Liu, Shoujie; Zheng, Xusheng; Song, Li; Liu, Wei; Yao, Tao; Sun, Zhihu; Lin, Yue; Wei, Shiqiang

    2016-05-01

    An effective strategy involving the corrosion of partial-surface-passivated Cu nanoparticles is proposed for synthesizing transition-metal-based Cu-Au alloy nanocages. Time-dependent X-ray absorption spectroscopy demonstrates that the hollow-cage Cu-Au alloy nanostructure is formed by sequential erosion of the partial surface and interior Cu and by the alloying of Au and Cu. PMID:27116561

  7. Sverdrup's Biology

    NASA Astrophysics Data System (ADS)

    McGowan, J.

    2002-12-01

    Sverdrup's contribution to Biological Oceanography were more than merely substantial, they were of fundamental importance. His plan for the training of graduate students at Scripps did not recognize the traditional division of the basic disciplines into separate categories of physics, chemistry, biology and geology. He insisted that Oceanography was a multi-disciplinary subject and that all entering students should study all four subjects. Today this is not very unusual but it was in the early 50s when I took those courses. We biologists carried away from those courses an appreciation of the importance of both spatial and temporal scale. It was of clear relevance to problems of oceanic population and community biology. But there was still more to his biology. He is responsible for a very simple, but very elegant model of the regulation of oceanic primary productivity. The elements of this model are found today in the ten or so highly derivative models. He also published a map predicting global ocean productivity based on the ideas in the model plus some wonderfully intuitive thinking. This map does not differ strongly from those glorious false color ones being published today.

  8. Bivalent metal-based MIL-53 analogues: Synthesis, properties and application

    NASA Astrophysics Data System (ADS)

    Liu, Yongxin; Liu, Dan; Wang, Cheng

    2015-03-01

    Trivalent metal-based MIL-53 (Al3+, Cr3+, Fe3+, In3+) compounds are interesting metal-organic frameworks (MOFs) with breathing effect and are promising gas sorption materials. Replacing bridging μ2-OH group by neutral ligands such as pyridine N-oxide and its derivatives (PNOs), the trivalent metal-based MIL-53 analogous structures could be extended to bivalent metal systems. The introduction of PNOs and bivalent metal elements endows the frameworks with new structural features and physical and chemical properties. This minireview summarizes the recent development of bivalent metal-based MIL-53 analogues (Mn2+, Co2+, Ni2+), typically, focusing on the synthetic strategies and potential applications based on our own works and literatures. We present the synthetic strategy to achieve structures evolution from single-ligand-walled to double-ligand-walled channel. Properties and application of these new materials in a wide range of potential areas are discussed including thermal stability, gas adsorption, magnetism and liquid-phase separation. Promising directions of this research field are also highlighted.

  9. Bioinformatics and School Biology

    ERIC Educational Resources Information Center

    Dalpech, Roger

    2006-01-01

    The rapidly changing field of bioinformatics is fuelling the need for suitably trained personnel with skills in relevant biological "sub-disciplines" such as proteomics, transcriptomics and metabolomics, etc. But because of the complexity--and sheer weight of data--associated with these new areas of biology, many school teachers feel…

  10. Load-bearing capacity and biological allowable limit of biodegradable metal based on degradation rate in vivo.

    PubMed

    Cho, Sung Youn; Chae, Soo-Won; Choi, Kui Won; Seok, Hyun Kwang; Han, Hyung Seop; Yang, Seok Jo; Kim, Young Yul; Kim, Jong Tac; Jung, Jae Young; Assad, Michel

    2012-08-01

    In this study, a newly developed Mg-Ca-Zn alloy for low degradation rate and surface erosion properties was evaluated. The compressive, tensile, and fatigue strength were measured before implantation. The degradation behavior was evaluated by analyzing the microstructure and local hardness of the explanted specimen. Mean and maximum degradation rates were measured using micro CT equipment from 4-, 8-, and 16- week explants, and the alloy was shown to display surface erosion properties. Based on these characteristics, the average and minimum load bearing capacities in tension, compression, and bending modes were calculated. According to the degradation rate and references of recommended dietary intakes (RDI), the Mg-Ca-Zn alloy appears to be safe for human use. PMID:22689439

  11. Ceramics reinforced metal base composite coatings produced by CO II laser cladding

    NASA Astrophysics Data System (ADS)

    Yang, Xichen; Wang, Yu; Yang, Nan

    2008-03-01

    Due to the excellent performance in high strength, anti-temperature and anti-wear, ceramics reinforced metal base composite material was used in some important fields of aircraft, aerospace, automobile and defense. The traditional bulk metal base composite materials are the expensive cost, which is limited in its industrial application. Development of laser coating of ceramics reinforced metal base composite is very interesting in economy. This paper is focused on three laser cladding ceramics coatings of SiC particle /Al matrix , Al IIO 3 powder/ Al matrix and WC + Co/mild steel matrix. Powder particle sizes are of 10-60μm. Chemical contents of aluminum matrix are of 3.8-4.0% Cu, 1.2-1.8% Mg, 0.3-0.99% Mn and balance Al. 5KW CO II laser, 5 axes CNC table, JKF-6 type powder feeder and co-axis feeder nozzle are used in laser cladding. Microstructure and performance of laser composite coatings have been respectively examined with OM,SEM and X-ray diffraction. Its results are as follows : Microstructures of 3C-,6H- and 5H- SiC particles + Al + Al 4SiC 4 + Si in SiC/Al composite, hexagonal α-Al IIO 3 + cubic γ-Al IIO 3 + f.c.c Al in Al IIO 3 powder/ Al composite and original WC particles + separated WC particles + eutectic WC + γ-Co solid solution + W IIC particles in WC + Co/steel coatings are respectively recognized. New microstructures of 5H-SiC in SiC/Al composite, cubic γ-Al IIO 3 in Al IIO 3 composite and W IIC in WC + Co/ steel composite by laser cladding have been respectively observed.

  12. Relevance, Derogation and Permission

    NASA Astrophysics Data System (ADS)

    Stolpe, Audun

    We show that a recently developed theory of positive permission based on the notion of derogation is hampered by a triviality result that indicates a problem with the underlying full-meet contraction operation. We suggest a solution that presupposes a particular normal form for codes of norms, adapted from the theory of relevance through propositional letter sharing. We then establish a correspondence between contractions on sets of norms in input/output logic (derogations), and AGM-style contractions on sets of formulae, and use it as a bridge to migrate results on propositional relevance from the latter to the former idiom. Changing the concept accordingly we show that positive permission now incorporates a relevance requirement that wards off triviality.

  13. Integrated Design and Rapid Development of Refractory Metal Based Alloys for Fossil Energy Applications

    SciTech Connect

    Dogan, O.N.; King, P.E.; Gao, M.C.

    2008-07-01

    One common barrier in the development of new technologies for future energy generating systems is insufficiency of existing materials at high temperatures (>1150oC) and aggressive atmospheres (e.g., steam, oxygen, CO2). To overcome this barrier, integrated design methodology will be applied to the development of refractory metal based alloys. The integrated design utilizes the multi-scale computational methods to design materials for requirements of processing and performance. This report summarizes the integrated design approach to the alloy development and project accomplishments in FY 2008.

  14. High-energy in-beam neutron measurements of metal-based shielding for accelerator-driven spallation neutron sources

    NASA Astrophysics Data System (ADS)

    DiJulio, D. D.; Cooper-Jensen, C. P.; Björgvinsdóttir, H.; Kokai, Z.; Bentley, P. M.

    2016-05-01

    Metal-based shielding plays an important role in the attenuation of harmful and unwanted radiation at an accelerator-driven spallation neutron source. At the European Spallation Source, currently under construction in Lund, Sweden, metal-based materials are planned to be used extensively as neutron guide substrates in addition to other shielding structures around neutron guides. The usage of metal-based materials in the vicinity of neutron guides however requires careful consideration in order to minimize potential background effects in a neutron instrument at the facility. Therefore, we have carried out a combined study involving high-energy neutron measurements and Monte Carlo simulations of metal-based shielding, both to validate the simulation methodology and also to investigate the benefits and drawbacks of different metal-based solutions. The measurements were carried out at The Svedberg Laboratory in Uppsala, Sweden, using a 174.1 MeV neutron beam and various thicknesses of aluminum-, iron-, and copper-based shielding blocks. The results were compared to geant4 simulations and revealed excellent agreement. Our combined study highlights the particular situations where one type of metal-based solution may be preferred over another.

  15. Implementation and performance evaluation of a database of chemical formulas for the screening of pharmaco/toxicologically relevant compounds in biological samples using electrospray ionization-time-of-flight mass spectrometry.

    PubMed

    Polettini, Aldo; Gottardo, Rossella; Pascali, Jennifer Paola; Tagliaro, Franco

    2008-04-15

    Electrospray ionization (ESI)-time-of-flight (TOF) MS enables searching a wide number of pharmaco/toxicologically relevant compounds (PTRC) in biosamples. However, the number of identifiable PTRC depends on extension of reference database of chemical formulas/compound names. Previous approaches proposed in-house or commercial databases with limitations either in PTRC number or content (e.g., few metabolites, presence of non-PTRC). In the frame of development of a ESI-TOF PTRC screening procedure, a subset of PubChem Compound as reference database is proposed. Features of this database (approximately 50,500 compounds) are illustrated, and its performance evaluated through analysis by capillary electrophoresis (CE)-ESI-TOF of hair/blood/urine collected from subjects under treatment with known drugs or by comparison with reference standards. The database is rich in parent compounds of pharmaceutical and illicit drugs, pesticides, and poisons and contains many metabolites (including about 6000 phase I metabolites and 180 glucuronides) and related substances (e.g., impurities, esters). The average number of hits with identical chemical formula is 1.82 +/- 2.27 (median = 1, range 1-39). Minor deficiencies, redundancies, and errors have been detected that do not limit the potential of the database in identifying unknown PTRC. The database allows a much broader search for PTRC than other commercial/in-house databases of chemical formulas/compound names previously proposed. However, the probability that a search retrieves different PTRC having identical chemical formula is higher than with smaller databases, and additional information (anamnestic/circumstantial data, concomitant presence of parent drug and metabolite, selective sample preparation, liquid chromatographic retention, and CE migration behavior) must be used in order to focus the search more tightly. PMID:18336013

  16. Core Bioactive Components Promoting Blood Circulation in the Traditional Chinese Medicine Compound Xueshuantong Capsule (CXC) Based on the Relevance Analysis between Chemical HPLC Fingerprint and In Vivo Biological Effects

    PubMed Central

    Liu, Hong; Liang, Jie-ping; Li, Pei-bo; Peng, Wei; Peng, Yao-yao; Zhang, Gao-min; Xie, Cheng-shi; Long, Chao-feng; Su, Wei-wei

    2014-01-01

    Compound xueshuantong capsule (CXC) is an oral traditional Chinese herbal formula (CHF) comprised of Panax notoginseng (PN), Radix astragali (RA), Salvia miltiorrhizae (SM), and Radix scrophulariaceae (RS). The present investigation was designed to explore the core bioactive components promoting blood circulation in CXC using high-performance liquid chromatography (HPLC) and animal studies. CXC samples were prepared with different proportions of the 4 herbs according to a four-factor, nine-level uniform design. CXC samples were assessed with HPLC, which identified 21 components. For the animal experiments, rats were soaked in ice water during the time interval between two adrenaline hydrochloride injections to reduce blood circulation. We assessed whole-blood viscosity (WBV), erythrocyte aggregation and red corpuscle electrophoresis indices (EAI and RCEI, respectively), plasma viscosity (PV), maximum platelet aggregation rate (MPAR), activated partial thromboplastin time (APTT), and prothrombin time (PT). Based on the hypothesis that CXC sample effects varied with differences in components, we performed grey relational analysis (GRA), principal component analysis (PCA), ridge regression (RR), and radial basis function (RBF) to evaluate the contribution of each identified component. Our results indicate that panaxytriol, ginsenoside Rb1, angoroside C, protocatechualdehyde, ginsenoside Rd, and calycosin-7-O-β-D-glucoside are the core bioactive components, and that they might play different roles in the alleviation of circulation dysfunction. Panaxytriol and ginsenoside Rb1 had close relevance to red blood cell (RBC) aggregation, angoroside C was related to platelet aggregation, protocatechualdehyde was involved in intrinsic clotting activity, ginsenoside Rd affected RBC deformability and plasma proteins, and calycosin-7-O-β-D-glucoside influenced extrinsic clotting activity. This study indicates that angoroside C, calycosin-7-O-β-D-glucoside, panaxytriol, and

  17. Blending Rigor and Relevance

    ERIC Educational Resources Information Center

    Siri, Diane K.; Zinner, Jane; Lezin, Nicole

    2011-01-01

    A collaborative at several sites across the state of California will offer evidence of how successful linked learning, which connects academics to real-world work, can be. This article presents examples that illustrate the powerful connections and linkages that are generated by combining academic rigor with the relevance of applying learning to…

  18. Is Information Still Relevant?

    ERIC Educational Resources Information Center

    Ma, Lia

    2013-01-01

    Introduction: The term "information" in information science does not share the characteristics of those of a nomenclature: it does not bear a generally accepted definition and it does not serve as the bases and assumptions for research studies. As the data deluge has arrived, is the concept of information still relevant for information…

  19. The Relevance of Literature.

    ERIC Educational Resources Information Center

    Dunham, L. L.

    1971-01-01

    The "legacy" of the humanities is discussed in terms of relevance, involvement, and other philosophical considerations. Reasons for studying foreign literature in language classes are developed in the article. Comment is also made on attitudes and ideas culled from the writings of Clifton Fadiman, Jean Paul Sartre, and James Baldwin. (RL)

  20. Reading, Writing and Relevance.

    ERIC Educational Resources Information Center

    Hoffman, Mary

    This monograph presents classroom activities that were designed to encourage children to read and write in a self-reliant and responsible manner. The activities were chosen for their relevance to the children involved and because the vocabulary involved was interesting, familiar, and worth remembering and using again. The topics are arranged in…

  1. Theoretical investigation of all-metal-based mushroom plasmonic metamaterial absorbers at infrared wavelengths

    NASA Astrophysics Data System (ADS)

    Ogawa, Shinpei; Fujisawa, Daisuke; Kimata, Masafumi

    2015-12-01

    High-performance wavelength-selective infrared (IR) sensors require small pixel structures, a low-thermal mass, and operation in the middle-wavelength infrared (MWIR) and long-wavelength infrared (LWIR) regions for multicolor IR imaging. All-metal-based mushroom plasmonic metamaterial absorbers (MPMAs) were investigated theoretically and were designed to enhance the performance of wavelength-selective uncooled IR sensors. All components of the MPMAs are based on thin layers of metals such as Au without oxide insulators for increased absorption. The absorption properties of the MPMAs were investigated by rigorous coupled-wave analysis. Strong wavelength-selective absorption is realized over a wide range of MWIR and LWIR wavelengths by the plasmonic resonance of the micropatch and the narrow-gap resonance, without disturbance from the intrinsic absorption of oxide insulators. The absorption wavelength is defined mainly by the micropatch size and is longer than its period. The metal post width has less impact on the absorption properties and can maintain single-mode operation. Through-holes can be formed on the plate area to reduce the thermal mass. A small pixel size with reduced thermal mass and wideband single-mode operation can be realized using all-metal-based MPMAs.

  2. Investigating extent of dissolved organic carbon stabilization by metal based coagulant in a wetland environment

    NASA Astrophysics Data System (ADS)

    Henneberry, Y.; Mourad, D.; Kraus, T.; Bachand, P.; Fujii, R.; Horwath, W.

    2008-12-01

    This study is part of a larger project designed to investigate the feasibility of using metal-based coagulants to remove dissolved organic carbon (DOC) from island drainage water in the San Joaquin Delta and subsequently retaining the metal-DOC precipitate (floc) in wetlands constructed at the foot of levees to promote levee stability. Dissolved organic carbon is a constituent of concern as some forms of DOC can be converted to carcinogenic compounds during drinking water treatment. The focus of this work is to assess floc stability over time and to determine whether floc can be permanently sequestered as part of wetland sediment. Drainage water collected seasonally from Twitchell Island was coagulated with ferric sulfate and polyaluminum chloride at optimal and 50%-optimal dosage levels. Floc was incubated in the laboratory under anaerobic conditions for six weeks under various conditions including different DOC concentrations, microbial inoculants, and addition of nutrients. Preliminary results indicate the floc is a stable system; little to no DOC was released from the floc into the water column under incubations with native microbial inoculate. In addition, floc incubated with previously coagulated water appeared to remove additional DOC from the water column. Future work will involve field and laboratory studies using 13C labeled plant material to examine the effects of fresh plant matter and the effects of peat soil DOC on floc stability, in order to elucidate mechanisms behind carbon stabilization by metal-based floc.

  3. One-pot green synthesis of biologically relevant novel spiro[indolin-2-one-3,4'-pyrano[2,3-c]pyrazoles] and studies on their spectral and X-ray crystallographic behaviors.

    PubMed

    Sharma, Sakshi; Brahmachari, Goutam; Kant, Rajni; Gupta, Vivek K

    2016-06-01

    Syntheses via green route and single-crystal X-ray structural investigations have been carried out for three spiro[indolin-2-one-3,4'-pyrano[2,3-c]pyrazole] derivatives, 6'-amino-2-oxo-3'-propyl-2'H-spiro[indoline-3,4'-pyrano[2,3-c]pyrazole]-5'-carbonitrile dimethyl sulfoxide monosolvate (5a), 6'-amino-5-fluoro-2-oxo-3'-propyl-2'H-spiro[indoline-3,4'-pyrano[2,3-c]pyrazole]-5'-carbonitrile dimethyl sulfoxide monosolvate (5b) and methyl 6'-amino-5-cyano-1-methyl-2-oxo-3'-propyl-2'H-spiro[indoline-3,4'-pyrano[2,3-c]pyrazole]-3'-carboxylate 0.25 hydrate (5c), respectively. Compounds (5a) and (5b) crystallize in the triclinic space group P\\bar 1, whereas compound (5c) crystallizes in the monoclinic space group C2/c. In molecules (5a) and (5b) all the rings are practically flat, while in (5c), the heterocyclic pyran ring adopts a flattened-boat conformation. In (5a) and (5b) the cyanide group is oriented in a (-ap) conformation, while the amino group is oriented in a (+ap) conformation with a pyran ring, but in (5c) both the cyanide and amino groups are oriented in a (-ap) conformation with the pyran ring. In the crystal structure of (5a) and (5b), the molecules are linked by an elaborate system of N-H...O and N-H...N hydrogen bonds to generate a zigzag-like construct. In (5c) molecules are linked by N-H...O hydrogen bonds, thereby generating extended chains. The present communication focuses on the detailed and comparative information about spectral behaviors, single-crystal X-ray crystallographic properties and solid-state supramolecular architectures of these synthesized compounds of potential biological interests. PMID:27240765

  4. Noble metal based plasmonic nanomaterials and their application for bio-imaging and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Zhu, Dewei

    During the past two decades, researchers have gained more and more insight into the manipulation of nanomaterials to create useful technologies. Numerous classes of nanomaterials have been produced and studied based upon their intriguing chemical and physical properties and their potential applications in diverse fields, ranging from electronics to renewable energy and biomedicine. In this dissertation, we describe the synthesis and potential biomedical applications of several types of noble metal-based nanomaterials in which we control size, shape, and coupling to other materials to tune their localized surface plasmon resonance (LSPR) interaction with light. We demonstrate the application of these novel nanostructures as contrast agents for photoacoustic imaging and as photosensitizers for photothermal therapy. Chapter one first presents protocols for producing monodisperse spherical nanoparticles of gold and silver. The diameter of the nanospheres can be adjusted from less than 2 nm to greater than 10 nm by controlling the reaction conditions, including ligands that cap the nanosphere surfaces, reaction time, and reaction temperature. Next, we describe the synthesis of multi-branched Au nanocrystals with predominantly tripodal, tetrapodal and star-shaped morphologies. We demonstrate tuning of the LSPR energy in these materials by changing the branch length. In the third part of this chapter, we present a novel method for coupling heavily-doped p-type copper selenide (Cu2-xSe) NPs with Au NPs by seeded nanocrystal growth to form a new type of semiconductor-metal heterogeneous nanostructure. This new class of plasmonic nanomaterials can simultaneously exhibit two types of LSPR in a single system, producing a broad optical absorbance that is nearly flat across the near infrared (NIR) spectral region (750-1150nm), along with a small shoulder at 566 nm that originates from the Au NP. We conclude this first chapter by demonstrating the use of self-doped copper sulfide

  5. Noble metal based plasmonic nanomaterials and their application for bio-imaging and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Zhu, Dewei

    During the past two decades, researchers have gained more and more insight into the manipulation of nanomaterials to create useful technologies. Numerous classes of nanomaterials have been produced and studied based upon their intriguing chemical and physical properties and their potential applications in diverse fields, ranging from electronics to renewable energy and biomedicine. In this dissertation, we describe the synthesis and potential biomedical applications of several types of noble metal-based nanomaterials in which we control size, shape, and coupling to other materials to tune their localized surface plasmon resonance (LSPR) interaction with light. We demonstrate the application of these novel nanostructures as contrast agents for photoacoustic imaging and as photosensitizers for photothermal therapy. Chapter one first presents protocols for producing monodisperse spherical nanoparticles of gold and silver. The diameter of the nanospheres can be adjusted from less than 2 nm to greater than 10 nm by controlling the reaction conditions, including ligands that cap the nanosphere surfaces, reaction time, and reaction temperature. Next, we describe the synthesis of multi-branched Au nanocrystals with predominantly tripodal, tetrapodal and star-shaped morphologies. We demonstrate tuning of the LSPR energy in these materials by changing the branch length. In the third part of this chapter, we present a novel method for coupling heavily-doped p-type copper selenide (Cu2-xSe) NPs with Au NPs by seeded nanocrystal growth to form a new type of semiconductor-metal heterogeneous nanostructure. This new class of plasmonic nanomaterials can simultaneously exhibit two types of LSPR in a single system, producing a broad optical absorbance that is nearly flat across the near infrared (NIR) spectral region (750-1150nm), along with a small shoulder at 566 nm that originates from the Au NP. We conclude this first chapter by demonstrating the use of self-doped copper sulfide

  6. Biological Threats

    MedlinePlus

    ... Thunderstorms & Lightning Tornadoes Tsunamis Volcanoes Wildfires Main Content Biological Threats Biological agents are organisms or toxins that ... Centers for Disease Control and Prevention . Before a Biological Threat Unlike an explosion, a biological attack may ...

  7. Experimental technique for studying high-temperature phase equilibria in reactive molten metal based systems

    NASA Astrophysics Data System (ADS)

    Ermoline, Alexandre

    The general objective of this work is to develop an experimental technique for studying the high-temperature phase compositions and phase equilibria in molten metal-based binary and ternary systems, such as Zr-O-N, B-N-O, Al-O, and others. A specific material system of Zr-O-N was selected for studying and testing this technique. The information about the high-temperature phase equilibria in reactive metal-based systems is scarce and their studying is difficult because of chemical reactions occurring between samples and essentially any container materials, and causing contamination of the system. Containerless microgravity experiments for studying equilibria in molten metal-gas systems were designed to be conducted onboard of a NASA KC-135 aircraft flying parabolic trajectories. A uniaxial apparatus suitable for acoustic levitation, laser heating, and splat quenching of small samples was developed and equipped with computer-based controller and optical diagnostics. Normal-gravity tests were conducted to determine the most suitable operating parameters of the levitator by direct observations of the levitated samples, as opposed to more traditional pressure mapping of the acoustic field. The size range of samples that could be reliably heated and quenched in this setup was determined to be on the order of 1--3 mm. In microgravity experiments, small spherical specimens (1--2 mm diameter), prepared as pressed, premixed solid components, ZrO2, ZrN, and Zr powders, were acoustically levitated inside an argon-filled chamber at one atmosphere and heated by a CO2 laser. The levitating samples could be continuously laser heated for about 1 sec, resulting in local sample melting. The sample stability in the vertical direction was undisturbed by simultaneous laser heating. Oscillations of the levitating sample in the horizontal direction increased while it was heated, which eventually resulted in the movement of the sample away from its stable levitation position and the laser

  8. Computational Systems Chemical Biology

    PubMed Central

    Oprea, Tudor I.; May, Elebeoba E.; Leitão, Andrei; Tropsha, Alexander

    2013-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007). The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology / systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology. PMID:20838980

  9. Insights on Metal Based Dental Implants and their Interaction with the Surrounding Tissues.

    PubMed

    Popa, Marcela; Hussien, Mohamed D; Cirstea, Alexandra; Grigore, Raluca; Lazar, Veronica; Bezirtzoglou, Eugenia; Chifiriuc, Mariana Carmen; Sakizlian, Monica; Stavropoulou, Elisavet; Bertesteanu, Serban

    2015-01-01

    At present, the use of dental implants is a very common practice as tooth loss is a frequent problem and can occur as a result of disease or trauma. An implant is usually made of biocompatible materials that do not cause rejection reactions and allow the implant union with the respective bone. To achieve this goal, the implant surface may have different structures and coatings, generally used to increase the adherence of the implant to the bone and to decrease the risk of the periimplantar inflammatory reactions. This review gives some insights of the metal based materials used for dental implants, their limits, improvement strategies as well as the pathophysiology, diagnosis, treatment and prevention of periimplantary diseases. PMID:25877088

  10. Quasiparticle band structure of the almost-gapless transition-metal-based Heusler semiconductors

    NASA Astrophysics Data System (ADS)

    Tas, M.; Şaşıoǧlu, E.; Galanakis, I.; Friedrich, C.; Blügel, S.

    2016-05-01

    Transition-metal-based Heusler semiconductors are promising materials for a variety of applications ranging from spintronics to thermoelectricity. Employing the G W approximation within the framework of the FLAPW method, we study the quasiparticle band structure of a number of such compounds being almost gapless semiconductors. We find that in contrast to the s p -electron based semiconductors such as Si and GaAs, in these systems, the many-body corrections have a minimal effect on the electronic band structure and the energy band gap increases by less than 0.2 eV, which makes the starting point density functional theory (DFT) a good approximation for the description of electronic and optical properties of these materials. Furthermore, the band gap can be tuned either by the variation of the lattice parameter or by the substitution of the s p -chemical element.