Endotoxin contamination: a key element in the interpretation of nanosafety studies.

PubMed

Li, Yang; Boraschi, Diana

2016-02-01

The study of toxicity and potential risks of engineered nanoparticles is of particular importance in nanomedicine. Endotoxin, a common contaminant of bacterial origin, has biological effects that can mask the true biological effects of nanoparticles, if its presence is overlooked. In this review, we report the features of nanoparticle contamination by endotoxin, and the different biological effects of endotoxin-contaminated nanoparticles. We will describe different methods for endotoxin detection applied to nanoparticles, and discuss their pros and cons. Eventually, we describe various methods for eliminating endotoxin contamination in nanoparticles. Although there is no universal technique for efficiently removing endotoxin from nanoparticles, specific solutions can be found case by case, which can allow us to perform nanosafety studies in biologically relevant conditions.

Dissecting the genetics of the human transcriptome identifies novel trait-related trans-eQTLs and corroborates the regulatory relevance of non-protein coding loci†

PubMed Central

Kirsten, Holger; Al-Hasani, Hoor; Holdt, Lesca; Gross, Arnd; Beutner, Frank; Krohn, Knut; Horn, Katrin; Ahnert, Peter; Burkhardt, Ralph; Reiche, Kristin; Hackermüller, Jörg; Löffler, Markus; Teupser, Daniel; Thiery, Joachim; Scholz, Markus

2015-01-01

Genetics of gene expression (eQTLs or expression QTLs) has proved an indispensable tool for understanding biological pathways and pathomechanisms of trait-associated SNPs. However, power of most genome-wide eQTL studies is still limited. We performed a large eQTL study in peripheral blood mononuclear cells of 2112 individuals increasing the power to detect trans-effects genome-wide. Going beyond univariate SNP-transcript associations, we analyse relations of eQTLs to biological pathways, polygenetic effects of expression regulation, trans-clusters and enrichment of co-localized functional elements. We found eQTLs for about 85% of analysed genes, and 18% of genes were trans-regulated. Local eSNPs were enriched up to a distance of 5 Mb to the transcript challenging typically implemented ranges of cis-regulations. Pathway enrichment within regulated genes of GWAS-related eSNPs supported functional relevance of identified eQTLs. We demonstrate that nearest genes of GWAS-SNPs might frequently be misleading functional candidates. We identified novel trans-clusters of potential functional relevance for GWAS-SNPs of several phenotypes including obesity-related traits, HDL-cholesterol levels and haematological phenotypes. We used chromatin immunoprecipitation data for demonstrating biological effects. Yet, we show for strongly heritable transcripts that still little trans-chromosomal heritability is explained by all identified trans-eSNPs; however, our data suggest that most cis-heritability of these transcripts seems explained. Dissection of co-localized functional elements indicated a prominent role of SNPs in loci of pseudogenes and non-coding RNAs for the regulation of coding genes. In summary, our study substantially increases the catalogue of human eQTLs and improves our understanding of the complex genetic regulation of gene expression, pathways and disease-related processes. PMID:26019233

How causal analysis can reveal autonomy in models of biological systems

NASA Astrophysics Data System (ADS)

Marshall, William; Kim, Hyunju; Walker, Sara I.; Tononi, Giulio; Albantakis, Larissa

2017-11-01

Standard techniques for studying biological systems largely focus on their dynamical or, more recently, their informational properties, usually taking either a reductionist or holistic perspective. Yet, studying only individual system elements or the dynamics of the system as a whole disregards the organizational structure of the system-whether there are subsets of elements with joint causes or effects, and whether the system is strongly integrated or composed of several loosely interacting components. Integrated information theory offers a theoretical framework to (1) investigate the compositional cause-effect structure of a system and to (2) identify causal borders of highly integrated elements comprising local maxima of intrinsic cause-effect power. Here we apply this comprehensive causal analysis to a Boolean network model of the fission yeast (Schizosaccharomyces pombe) cell cycle. We demonstrate that this biological model features a non-trivial causal architecture, whose discovery may provide insights about the real cell cycle that could not be gained from holistic or reductionist approaches. We also show how some specific properties of this underlying causal architecture relate to the biological notion of autonomy. Ultimately, we suggest that analysing the causal organization of a system, including key features like intrinsic control and stable causal borders, should prove relevant for distinguishing life from non-life, and thus could also illuminate the origin of life problem. This article is part of the themed issue 'Reconceptualizing the origins of life'.

Robust k-mer frequency estimation using gapped k-mers

PubMed Central

Ghandi, Mahmoud; Mohammad-Noori, Morteza

2013-01-01

Oligomers of fixed length, k, commonly known as k-mers, are often used as fundamental elements in the description of DNA sequence features of diverse biological function, or as intermediate elements in the constuction of more complex descriptors of sequence features such as position weight matrices. k-mers are very useful as general sequence features because they constitute a complete and unbiased feature set, and do not require parameterization based on incomplete knowledge of biological mechanisms. However, a fundamental limitation in the use of k-mers as sequence features is that as k is increased, larger spatial correlations in DNA sequence elements can be described, but the frequency of observing any specific k-mer becomes very small, and rapidly approaches a sparse matrix of binary counts. Thus any statistical learning approach using k-mers will be susceptible to noisy estimation of k-mer frequencies once k becomes large. Because all molecular DNA interactions have limited spatial extent, gapped k-mers often carry the relevant biological signal. Here we use gapped k-mer counts to more robustly estimate the ungapped k-mer frequencies, by deriving an equation for the minimum norm estimate of k-mer frequencies given an observed set of gapped k-mer frequencies. We demonstrate that this approach provides a more accurate estimate of the k-mer frequencies in real biological sequences using a sample of CTCF binding sites in the human genome. PMID:23861010

Robust k-mer frequency estimation using gapped k-mers.

PubMed

Ghandi, Mahmoud; Mohammad-Noori, Morteza; Beer, Michael A

2014-08-01

Oligomers of fixed length, k, commonly known as k-mers, are often used as fundamental elements in the description of DNA sequence features of diverse biological function, or as intermediate elements in the constuction of more complex descriptors of sequence features such as position weight matrices. k-mers are very useful as general sequence features because they constitute a complete and unbiased feature set, and do not require parameterization based on incomplete knowledge of biological mechanisms. However, a fundamental limitation in the use of k-mers as sequence features is that as k is increased, larger spatial correlations in DNA sequence elements can be described, but the frequency of observing any specific k-mer becomes very small, and rapidly approaches a sparse matrix of binary counts. Thus any statistical learning approach using k-mers will be susceptible to noisy estimation of k-mer frequencies once k becomes large. Because all molecular DNA interactions have limited spatial extent, gapped k-mers often carry the relevant biological signal. Here we use gapped k-mer counts to more robustly estimate the ungapped k-mer frequencies, by deriving an equation for the minimum norm estimate of k-mer frequencies given an observed set of gapped k-mer frequencies. We demonstrate that this approach provides a more accurate estimate of the k-mer frequencies in real biological sequences using a sample of CTCF binding sites in the human genome.

Investigating the transcriptional control of cardiovascular development

PubMed Central

Kathiriya, Irfan S.; Nora, Elphege P.; Bruneau, Benoit G.

2015-01-01

Transcriptional regulation of thousands of genes instructs complex morphogenetic and molecular events for heart development. Cardiac transcription factors (TFs) choreograph gene expression at each stage of differentiation by interacting with co-factors, including chromatin-modifying enzymes, and by binding to a constellation of regulatory DNA elements. Here, we present salient examples relevant to cardiovascular development and heart disease and review techniques that can sharpen our understanding of cardiovascular biology. We discuss the interplay between cardiac TFs, cis-regulatory elements and chromatin as dynamic regulatory networks, to orchestrate sequential deployment of the cardiac gene expression program. PMID:25677518

JPRS Report, Proliferation Issues

DTIC Science & Technology

1991-08-08

from its processing plant at Valindaba, and fuel-fabrication plants at Valindaba and Pelindaba. where fuel rods for use at the Koeberg nuclear-power...construction of the fourth one. The pulsed reactor uses special elements of nuclear fuel The site of the proposed fourth nuclear power plant can enabling...chemical, and biological weapons, including delivery systems and the transfer of weapons-relevant technologies.] AFRICA SOUTH AFRICA Civilian Uses for

Allometry and apparent paradoxes in human limb proportions: Implications for scaling factors.

PubMed

Auerbach, Benjamin M; Sylvester, Adam D

2011-03-01

It has been consistently demonstrated that human proximal limb elements exhibit negative allometry, while distal elements scale with positive allometry. Such scaling implies that longer limbs will have higher intralimb indices, a phenomenon not borne out by empirical analyses. This, therefore, creates a paradox within the limb allometry literature. This study shows that these apparently conflicting results are the product of two separate phenomena. First, the use of the geometric mean of limb elements produces allometry coefficients that are not independent, and that when using ordinary least squares regression must yield an average slope of one. This phenomenon argues against using the geometric mean as a size variable when examining limb allometry. While the employment of relevant dimensions independent of those under analysis to calculate the geometric mean--as suggested by Coleman (Am J Phys Anthropol 135 (2008) 404-415)--may be a partial method for resolving the problem, an empirically determined, independent and biologically relevant size variable is advocated. If stature is used instead of the geometric mean as an independent size variable, all major limb elements scale with positive allometry. Second, while limb allometry coefficients do indicate differential allometry in limb elements, and thus should lead to some intralimb index allometry, this pattern appears to be attenuated by other sources of limb element length variation. Copyright © 2010 Wiley-Liss, Inc.

Dynamics and biological relevance of DNA demethylation in Arabidopsis antibacterial defense.

PubMed

Yu, Agnès; Lepère, Gersende; Jay, Florence; Wang, Jingyu; Bapaume, Laure; Wang, Yu; Abraham, Anne-Laure; Penterman, Jon; Fischer, Robert L; Voinnet, Olivier; Navarro, Lionel

2013-02-05

DNA methylation is an epigenetic mark that silences transposable elements (TEs) and repeats. Whereas the establishment and maintenance of DNA methylation are relatively well understood, little is known about their dynamics and biological relevance in plant and animal innate immunity. Here, we show that some TEs are demethylated and transcriptionally reactivated during antibacterial defense in Arabidopsis. This effect is correlated with the down-regulation of key transcriptional gene silencing factors and is partly dependent on an active demethylation process. DNA demethylation restricts multiplication and vascular propagation of the bacterial pathogen Pseudomonas syringae in leaves and, accordingly, some immune-response genes, containing repeats in their promoter regions, are negatively regulated by DNA methylation. This study provides evidence that DNA demethylation is part of a plant-induced immune response, potentially acting to prime transcriptional activation of some defense genes linked to TEs/repeats.

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

Making a protein extract from plant pathogenic fungi for gel- and LC-based proteomics.

PubMed

Fernández, Raquel González; Redondo, Inmaculada; Jorrin-Novo, Jesus V

2014-01-01

Proteomic technologies have become a successful tool to provide relevant information on fungal biology. In the case of plant pathogenic fungi, this approach would allow a deeper knowledge of the interaction and the biological cycle of the pathogen, as well as the identification of pathogenicity and virulence factors. These two elements open up new possibilities for crop disease diagnosis and environment-friendly crop protection. Phytopathogenic fungi, due to its particular cellular characteristics, can be considered as a recalcitrant biological material, which makes it difficult to obtain quality protein samples for proteomic analysis. This chapter focuses on protein extraction for gel- and LC-based proteomics with specific protocols of our current research with Botrytis cinerea.

A Drosophila LexA Enhancer-Trap Resource for Developmental Biology and Neuroendocrine Research

PubMed Central

Kockel, Lutz; Huq, Lutfi M.; Ayyar, Anika; Herold, Emma; MacAlpine, Elle; Logan, Madeline; Savvides, Christina; Kim, Grace E. S.; Chen, Jiapei; Clark, Theresa; Duong, Trang; Fazel-Rezai, Vahid; Havey, Deanna; Han, Samuel; Jagadeesan, Ravi; Kim, Eun Soo Jackie; Lee, Diane; Lombardo, Kaelina; Piyale, Ida; Shi, Hansen; Stahr, Lydia; Tung, Dana; Tayvah, Uriel; Wang, Flora; Wang, Ja-Hon; Xiao, Sarah; Topper, Sydni M.; Park, Sangbin; Rotondo, Cheryl; Rankin, Anne E.; Chisholm, Townley W.; Kim, Seung K.

2016-01-01

Novel binary gene expression tools like the LexA-LexAop system could powerfully enhance studies of metabolism, development, and neurobiology in Drosophila. However, specific LexA drivers for neuroendocrine cells and many other developmentally relevant systems remain limited. In a unique high school biology course, we generated a LexA-based enhancer trap collection by transposon mobilization. The initial collection provides a source of novel LexA-based elements that permit targeted gene expression in the corpora cardiaca, cells central for metabolic homeostasis, and other neuroendocrine cell types. The collection further contains specific LexA drivers for stem cells and other enteric cells in the gut, and other developmentally relevant tissue types. We provide detailed analysis of nearly 100 new LexA lines, including molecular mapping of insertions, description of enhancer-driven reporter expression in larval tissues, and adult neuroendocrine cells, comparison with established enhancer trap collections and tissue specific RNAseq. Generation of this open-resource LexA collection facilitates neuroendocrine and developmental biology investigations, and shows how empowering secondary school science can achieve research and educational goals. PMID:27527793

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.

A Drosophila LexA Enhancer-Trap Resource for Developmental Biology and Neuroendocrine Research.

PubMed

Kockel, Lutz; Huq, Lutfi M; Ayyar, Anika; Herold, Emma; MacAlpine, Elle; Logan, Madeline; Savvides, Christina; Kim, Grace E S; Chen, Jiapei; Clark, Theresa; Duong, Trang; Fazel-Rezai, Vahid; Havey, Deanna; Han, Samuel; Jagadeesan, Ravi; Kim, Eun Soo Jackie; Lee, Diane; Lombardo, Kaelina; Piyale, Ida; Shi, Hansen; Stahr, Lydia; Tung, Dana; Tayvah, Uriel; Wang, Flora; Wang, Ja-Hon; Xiao, Sarah; Topper, Sydni M; Park, Sangbin; Rotondo, Cheryl; Rankin, Anne E; Chisholm, Townley W; Kim, Seung K

2016-10-13

Novel binary gene expression tools like the LexA-LexAop system could powerfully enhance studies of metabolism, development, and neurobiology in Drosophila However, specific LexA drivers for neuroendocrine cells and many other developmentally relevant systems remain limited. In a unique high school biology course, we generated a LexA-based enhancer trap collection by transposon mobilization. The initial collection provides a source of novel LexA-based elements that permit targeted gene expression in the corpora cardiaca, cells central for metabolic homeostasis, and other neuroendocrine cell types. The collection further contains specific LexA drivers for stem cells and other enteric cells in the gut, and other developmentally relevant tissue types. We provide detailed analysis of nearly 100 new LexA lines, including molecular mapping of insertions, description of enhancer-driven reporter expression in larval tissues, and adult neuroendocrine cells, comparison with established enhancer trap collections and tissue specific RNAseq. Generation of this open-resource LexA collection facilitates neuroendocrine and developmental biology investigations, and shows how empowering secondary school science can achieve research and educational goals. Copyright © 2016 Kockel et al.

An analytical poroelastic model for ultrasound elastography imaging of tumors

NASA Astrophysics Data System (ADS)

Tauhidul Islam, Md; Chaudhry, Anuj; Unnikrishnan, Ginu; Reddy, J. N.; Righetti, Raffaella

2018-01-01

The mechanical behavior of biological tissues has been studied using a number of mechanical models. Due to the relatively high fluid content and mobility, many biological tissues have been modeled as poroelastic materials. Diseases such as cancers are known to alter the poroelastic response of a tissue. Tissue poroelastic properties such as compressibility, interstitial permeability and fluid pressure also play a key role for the assessment of cancer treatments and for improved therapies. At the present time, however, a limited number of poroelastic models for soft tissues are retrievable in the literature, and the ones available are not directly applicable to tumors as they typically refer to uniform tissues. In this paper, we report the analytical poroelastic model for a non-uniform tissue under stress relaxation. Displacement, strain and fluid pressure fields in a cylindrical poroelastic sample containing a cylindrical inclusion during stress relaxation are computed. Finite element simulations are then used to validate the proposed theoretical model. Statistical analysis demonstrates that the proposed analytical model matches the finite element results with less than 0.5% error. The availability of the analytical model and solutions presented in this paper may be useful to estimate diagnostically relevant poroelastic parameters such as interstitial permeability and fluid pressure, and, in general, for a better interpretation of clinically-relevant ultrasound elastography results.

Marine Bioinorganic Chemistry: The Role of Trace Metals in the Oceanic Cycles of Major Nutrients

NASA Astrophysics Data System (ADS)

Morel, F. M. M.; Milligan, A. J.; Saito, M. A.

2003-12-01

The bulk of living biomass is chiefly made up of only a dozen "major" elements - carbon, hydrogen, oxygen, nitrogen, phosphorus, sodium, potassium, chlorine, calcium, magnesium, sulfur (and silicon in diatoms) - whose proportions vary within a relatively narrow range in most organisms. A number of trace elements, particularly first row transition metals - manganese, iron, nickel, cobalt, copper, and zinc - are also "essential" for the growth of organisms. At the molecular level, the chemical mechanisms by which such elements function as active centers or structural factors in enzymes and by which they are accumulated and stored by organisms is the central topic of bioinorganic chemistry. At the scale of ocean basins, the interplay of physical, chemical, and biological processes that govern the cycling of biologically essential elements in seawater is the subject of marine biogeochemistry. For those interested in the growth of marine organisms, particularly in the one-half of the Earth's primary production contributed by marine phytoplankton, bioinorganic chemistry and marine biogeochemistry are critically linked by the extraordinary paucity of essential trace elements in surface seawater, which results from their biological utilization and incorporation in sinking organic matter. How marine organisms acquire elements that are present at nano- or picomolar concentrations in surface seawater; how they perform critical enzymatic functions when necessary metal cofactors are almost unavailable are the central topics of "marine bioinorganic chemistry." The central aim of this field is to elucidate at the molecular level the metal-dependent biological processes involved in the major biogeochemical cycles.By examining the solutions that emerged from the problems posed by the scarcity of essential trace elements, marine bioinorganic chemists bring to light hitherto unknown ways to take up or utilize trace elements, new molecules, and newer "essential" elements. Focusing on molecular mechanisms involved in such processes as inorganic carbon fixation, organic carbon respiration, or nitrogen transformation, they explain how the cycles of trace elements are critically linked to those of major nutrients such as carbon or nitrogen. But we have relatively little understanding of the binding molecules and the enzymes that mediate the biochemical role of trace metals in the marine environment. In this sense, this chapter is more a "preview" than a review of the field of marine bioinorganic chemistry. To exemplify the concepts and methods of this field, we have chosen to focus on one of its most important topics: the potentially limiting role of trace elements in primary marine production. As a result we center our discussion on particular subsets of organisms, biogeochemical cycles, and trace elements. Our chief actors are marine phytoplankton, particularly eukaryotes, while heterotrophic bacteria make only cameo appearances. The biogeochemical cycles that will serve as our plot are those of the elements involved in phytoplankton growth, the major algal nutrients - carbon, nitrogen, phosphorus, and silicon - leaving aside, e.g., the interesting topic of the marine sulfur cycle. Seven trace metals provide the intrigue: manganese, iron, nickel, cobalt, copper, zinc, and cadmium. But several other trace elements such as selenium, vanadium, molybdenum, and tungsten (and, probably, others not yet identified) will assuredly add further twists in future episodes.We begin this chapter by discussing what we know of the concentrations of trace elements in marine microorganisms and of the relevant mechanisms and kinetics of trace-metal uptake. We then review the biochemical role of trace elements in the marine cycles of carbon, nitrogen, phosphorus, and silicon. Using this information, we examine the evidence, emanating from both laboratory cultures and field measurements, relevant to the mechanisms and the extent of control by trace metals of marine biogeochemical cycles. Before concluding with a wistful glimpse of the future of marine bioinorganic chemistry we discuss briefly some paleoceanographic aspects of this new field: how the chemistry of the planet "Earth" - particularly the concentrations of trace elements in the oceans - has evolved since its origin, chiefly as a result of biological processes and how the evolution of life has, in turn, been affected by the availability of essential trace elements.

Biological forcing controls the chemistry of the coral exoskeleton

NASA Astrophysics Data System (ADS)

Meibom, A.; Mostefaoui, S.; Cuif, J.; Yurimoto, H.; Dauphin, Y.; Houlbreque, F.; Dunbar, R.; Constantz, B.

2006-12-01

A multitude of marine organisms produce calcium carbonate skeletons that are used extensively to reconstruct water temperature variability of the tropical and subtropical oceans - a key parameter in global climate-change models. Such paleo-climate reconstructions are based on the notion that skeletal oxygen isotopic composition and certain trace-element abundances (e.g., Sr/Ca and Mg/Ca ratios) vary in response to changes in the water temperature. However, it is a fundamental problem that poorly understood biological processes introduce large compositional deviations from thermodynamic equilibrium and hinder precise calibrations of many paleo-climate proxies. Indeed, the role of water temperature in controlling the composition of the skeleton is far from understood. We have studied trace-element abundances as well as oxygen and carbon isotopic compositions of individual skeletal components in the zooxanthellate and non-zooxanthellate corals at ultra-structural, i.e. micrometer to sub-micrometer length scales. From this body of work we draw the following, generalized conclusions: 1) Centers of calcification (COC) are not in equilibrium with seawater. Notably, the Sr/Ca ratio is higher than expected for aragonite equilibrium with seawater at the temperature at which the skeleton was formed. Furthermore, the COC are further away from equilibrium with seawater than fibrous skeleton in terms of stable isotope composition. 2) COC are dramatically different from the fibrous aragonite skeleton in terms of trace element composition. 3) Neither trace element nor stable isotope variations in the fibrous (bulk) part of the skeleton are directly related to changes in SST. In fact, changes in SST can have very little to do with the observed compositional variations. 4) Trace element variations in the fibrous (bulk) part of the skeleton are not related to the activity of zooxanthellae. These observations are directly relevant to the issue of biological versus non-biological control over skeleton composition and will be discussed.

Large Deformation Dynamic Three-Dimensional Coupled Finite Element Analysis of Soft Biological Tissues Treated as Biphasic Porous Media

DTIC Science & Technology

2014-11-01

response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and...over time , when a bipha- sic soft tissue is subjected to dynamic loading. Also, after the initial transient, the variation of solid skeleton stresses...will be naturally calculated as the fluid phase pressure dissipates over time . This is important for developing physiologically- relevant degradation

Dissecting the genetics of the human transcriptome identifies novel trait-related trans-eQTLs and corroborates the regulatory relevance of non-protein coding loci†.

PubMed

Kirsten, Holger; Al-Hasani, Hoor; Holdt, Lesca; Gross, Arnd; Beutner, Frank; Krohn, Knut; Horn, Katrin; Ahnert, Peter; Burkhardt, Ralph; Reiche, Kristin; Hackermüller, Jörg; Löffler, Markus; Teupser, Daniel; Thiery, Joachim; Scholz, Markus

2015-08-15

Genetics of gene expression (eQTLs or expression QTLs) has proved an indispensable tool for understanding biological pathways and pathomechanisms of trait-associated SNPs. However, power of most genome-wide eQTL studies is still limited. We performed a large eQTL study in peripheral blood mononuclear cells of 2112 individuals increasing the power to detect trans-effects genome-wide. Going beyond univariate SNP-transcript associations, we analyse relations of eQTLs to biological pathways, polygenetic effects of expression regulation, trans-clusters and enrichment of co-localized functional elements. We found eQTLs for about 85% of analysed genes, and 18% of genes were trans-regulated. Local eSNPs were enriched up to a distance of 5 Mb to the transcript challenging typically implemented ranges of cis-regulations. Pathway enrichment within regulated genes of GWAS-related eSNPs supported functional relevance of identified eQTLs. We demonstrate that nearest genes of GWAS-SNPs might frequently be misleading functional candidates. We identified novel trans-clusters of potential functional relevance for GWAS-SNPs of several phenotypes including obesity-related traits, HDL-cholesterol levels and haematological phenotypes. We used chromatin immunoprecipitation data for demonstrating biological effects. Yet, we show for strongly heritable transcripts that still little trans-chromosomal heritability is explained by all identified trans-eSNPs; however, our data suggest that most cis-heritability of these transcripts seems explained. Dissection of co-localized functional elements indicated a prominent role of SNPs in loci of pseudogenes and non-coding RNAs for the regulation of coding genes. In summary, our study substantially increases the catalogue of human eQTLs and improves our understanding of the complex genetic regulation of gene expression, pathways and disease-related processes. © The Author 2015. Published by Oxford University Press.

Genome-wide inference of regulatory networks in Streptomyces coelicolor.

PubMed

Castro-Melchor, Marlene; Charaniya, Salim; Karypis, George; Takano, Eriko; Hu, Wei-Shou

2010-10-18

The onset of antibiotics production in Streptomyces species is co-ordinated with differentiation events. An understanding of the genetic circuits that regulate these coupled biological phenomena is essential to discover and engineer the pharmacologically important natural products made by these species. The availability of genomic tools and access to a large warehouse of transcriptome data for the model organism, Streptomyces coelicolor, provides incentive to decipher the intricacies of the regulatory cascades and develop biologically meaningful hypotheses. In this study, more than 500 samples of genome-wide temporal transcriptome data, comprising wild-type and more than 25 regulatory gene mutants of Streptomyces coelicolor probed across multiple stress and medium conditions, were investigated. Information based on transcript and functional similarity was used to update a previously-predicted whole-genome operon map and further applied to predict transcriptional networks constituting modules enriched in diverse functions such as secondary metabolism, and sigma factor. The predicted network displays a scale-free architecture with a small-world property observed in many biological networks. The networks were further investigated to identify functionally-relevant modules that exhibit functional coherence and a consensus motif in the promoter elements indicative of DNA-binding elements. Despite the enormous experimental as well as computational challenges, a systems approach for integrating diverse genome-scale datasets to elucidate complex regulatory networks is beginning to emerge. We present an integrated analysis of transcriptome data and genomic features to refine a whole-genome operon map and to construct regulatory networks at the cistron level in Streptomyces coelicolor. The functionally-relevant modules identified in this study pose as potential targets for further studies and verification.

Fast X-Ray Fluorescence Microtomography of Hydrated Biological Samples

PubMed Central

Lombi, Enzo; de Jonge, Martin D.; Donner, Erica; Kopittke, Peter M.; Howard, Daryl L.; Kirkham, Robin; Ryan, Chris G.; Paterson, David

2011-01-01

Metals and metalloids play a key role in plant and other biological systems as some of them are essential to living organisms and all can be toxic at high concentrations. It is therefore important to understand how they are accumulated, complexed and transported within plants. In situ imaging of metal distribution at physiological relevant concentrations in highly hydrated biological systems is technically challenging. In the case of roots, this is mainly due to the possibility of artifacts arising during sample preparation such as cross sectioning. Synchrotron x-ray fluorescence microtomography has been used to obtain virtual cross sections of elemental distributions. However, traditionally this technique requires long data acquisition times. This has prohibited its application to highly hydrated biological samples which suffer both radiation damage and dehydration during extended analysis. However, recent advances in fast detectors coupled with powerful data acquisition approaches and suitable sample preparation methods can circumvent this problem. We demonstrate the heightened potential of this technique by imaging the distribution of nickel and zinc in hydrated plant roots. Although 3D tomography was still impeded by radiation damage, we successfully collected 2D tomograms of hydrated plant roots exposed to environmentally relevant metal concentrations for short periods of time. To our knowledge, this is the first published example of the possibilities offered by a new generation of fast fluorescence detectors to investigate metal and metalloid distribution in radiation-sensitive, biological samples. PMID:21674049

Elemental Analysis of Bone, Teeth, Horn and Antler in Different Animal Species Using Non-Invasive Handheld X-Ray Fluorescence.

PubMed

Buddhachat, Kittisak; Klinhom, Sarisa; Siengdee, Puntita; Brown, Janine L; Nomsiri, Raksiri; Kaewmong, Patcharaporn; Thitaram, Chatchote; Mahakkanukrauh, Pasuk; Nganvongpanit, Korakot

2016-01-01

Mineralized tissues accumulate elements that play crucial roles in animal health. Although elemental content of bone, blood and teeth of human and some animal species have been characterized, data for many others are lacking, as well as species comparisons. Here we describe the distribution of elements in horn (Bovidae), antler (Cervidae), teeth and bone (humerus) across a number of species determined by handheld X-ray fluorescence (XRF) to better understand differences and potential biological relevance. A difference in elemental profiles between horns and antlers was observed, possibly due to the outer layer of horns being comprised of keratin, whereas antlers are true bone. Species differences in tissue elemental content may be intrinsic, but also related to feeding habits that contribute to mineral accumulation, particularly for toxic heavy metals. One significant finding was a higher level of iron (Fe) in the humerus bone of elephants compared to other species. This may be an adaptation of the hematopoietic system by distributing Fe throughout the bone rather than the marrow, as elephant humerus lacks a marrow cavity. We also conducted discriminant analysis and found XRF was capable of distinguishing samples from different species, with humerus bone being the best source for species discrimination. For example, we found a 79.2% correct prediction and success rate of 80% for classification between human and non-human humerus bone. These findings show that handheld XRF can serve as an effective tool for the biological study of elemental composition in mineralized tissue samples and may have a forensic application.

Elemental Analysis of Bone, Teeth, Horn and Antler in Different Animal Species Using Non-Invasive Handheld X-Ray Fluorescence

PubMed Central

Buddhachat, Kittisak; Klinhom, Sarisa; Siengdee, Puntita; Brown, Janine L.; Nomsiri, Raksiri; Kaewmong, Patcharaporn; Thitaram, Chatchote; Mahakkanukrauh, Pasuk; Nganvongpanit, Korakot

2016-01-01

Mineralized tissues accumulate elements that play crucial roles in animal health. Although elemental content of bone, blood and teeth of human and some animal species have been characterized, data for many others are lacking, as well as species comparisons. Here we describe the distribution of elements in horn (Bovidae), antler (Cervidae), teeth and bone (humerus) across a number of species determined by handheld X-ray fluorescence (XRF) to better understand differences and potential biological relevance. A difference in elemental profiles between horns and antlers was observed, possibly due to the outer layer of horns being comprised of keratin, whereas antlers are true bone. Species differences in tissue elemental content may be intrinsic, but also related to feeding habits that contribute to mineral accumulation, particularly for toxic heavy metals. One significant finding was a higher level of iron (Fe) in the humerus bone of elephants compared to other species. This may be an adaptation of the hematopoietic system by distributing Fe throughout the bone rather than the marrow, as elephant humerus lacks a marrow cavity. We also conducted discriminant analysis and found XRF was capable of distinguishing samples from different species, with humerus bone being the best source for species discrimination. For example, we found a 79.2% correct prediction and success rate of 80% for classification between human and non-human humerus bone. These findings show that handheld XRF can serve as an effective tool for the biological study of elemental composition in mineralized tissue samples and may have a forensic application. PMID:27196603

Relevance and Significance of Extraterrestrial Abiological Hydrocarbon Chemistry.

PubMed

Olah, George A; Mathew, Thomas; Prakash, G K Surya

2016-06-08

Astrophysical observations show similarity of observed abiological "organics"-i.e., hydrocarbons, their derivatives, and ions (carbocations and carbanions)-with studied terrestrial chemistry. Their formation pathways, their related extraterrestrial hydrocarbon chemistry originating from carbon and other elements after the Big Bang, their parent hydrocarbon and derivative (methane and methanol, respectively), and transportation of derived building blocks of life by meteorites or comets to planet Earth are discussed in this Perspective. Their subsequent evolution on Earth under favorable "Goldilocks" conditions led to more complex molecules and biological systems, and eventually to humans. The relevance and significance of extraterrestrial hydrocarbon chemistry to the limits of science in relation to the physical aspects of evolution on our planet Earth are also discussed.

Target Discovery for Precision Medicine Using High-Throughput Genome Engineering.

PubMed

Guo, Xinyi; Chitale, Poonam; Sanjana, Neville E

2017-01-01

Over the past few years, programmable RNA-guided nucleases such as the CRISPR/Cas9 system have ushered in a new era of precision genome editing in diverse model systems and in human cells. Functional screens using large libraries of RNA guides can interrogate a large hypothesis space to pinpoint particular genes and genetic elements involved in fundamental biological processes and disease-relevant phenotypes. Here, we review recent high-throughput CRISPR screens (e.g. loss-of-function, gain-of-function, and targeting noncoding elements) and highlight their potential for uncovering novel therapeutic targets, such as those involved in cancer resistance to small molecular drugs and immunotherapies, tumor evolution, infectious disease, inborn genetic disorders, and other therapeutic challenges.

A functional metagenomic approach for expanding the synthetic biology toolbox for biomass conversion

PubMed Central

Sommer, Morten OA; Church, George M; Dantas, Gautam

2010-01-01

Sustainable biofuel alternatives to fossil fuel energy are hampered by recalcitrance and toxicity of biomass substrates to microbial biocatalysts. To address this issue, we present a culture-independent functional metagenomic platform for mining Nature's vast enzymatic reservoir and show its relevance to biomass conversion. We performed functional selections on 4.7 Gb of metagenomic fosmid libraries and show that genetic elements conferring tolerance toward seven important biomass inhibitors can be identified. We select two metagenomic fosmids that improve the growth of Escherichia coli by 5.7- and 6.9-fold in the presence of inhibitory concentrations of syringaldehyde and 2-furoic acid, respectively, and identify the individual genes responsible for these tolerance phenotypes. Finally, we combine the individual genes to create a three-gene construct that confers tolerance to mixtures of these important biomass inhibitors. This platform presents a route for expanding the repertoire of genetic elements available to synthetic biology and provides a starting point for efforts to engineer robust strains for biofuel generation. PMID:20393580

Using cell structures to develop functional nanomaterials and nanostructures--case studies of actin filaments and microtubules.

PubMed

Wu, Kevin Chia-Wen; Yang, Chung-Yao; Cheng, Chao-Min

2014-04-25

This article is based on the continued development of biologically relevant elements (i.e., actin filaments and microtubules in living cells) as building blocks to create functional nanomaterials and nanostructures that can then be used to manufacture nature-inspired small-scale devices or systems. Here, we summarize current progress in the field and focus specifically on processes characterized by (1) robustness and ease of use, (2) inexpensiveness, and (3) potential expandability to mass production. This article, we believe, will provide scientists and engineers with a more comprehensive understanding of how to mine biological materials and natural design features to construct functional materials and devices.

Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease.

PubMed

Torres, Matthew P; Dewhurst, Henry; Sundararaman, Niveda

2016-11-01

Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable body of potential regulatory elements that impact hundreds of different biological processes important in eukaryotic biology and human health. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Combining content and elements of communication into an upper-level biochemistry course.

PubMed

Whittington, Carli P; Pellock, Samuel J; Cunningham, Rebecca L; Cox, James R

2014-01-01

This report describes how a science communication module was incorporated into an advanced biochemistry course. Elements of communication were taught synergistically with biochemistry content in this course in an effort to expose students to a variety of effective oral communication strategies. Students were trained to use these established techniques and incorporated them into various presentations throughout the course. Three students describe their use of specific resources and how the skills learned relate to their future career. The importance and relevance of science communication are receiving unprecedented national attention. The academic scientific community must respond by incorporating more communication-centered instruction and opportunities in the classroom and laboratory. © 2013 by The International Union of Biochemistry and Molecular Biology.

Nuclear analytical techniques in medicine

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

Cesareo, R.

1988-01-01

This book acquaints one with the fundamental principles and the instrumentation relevant to analytical technique based on atomic and nuclear physics, as well as present and future biomedical applications. Besides providing a theoretical description of the physical phenomena, a large part of the book is devoted to applications in the medical and biological field, particularly in hematology, forensic medicine and environmental science. This volume reviews methods such as the possibility of carrying out rapid multi-element analysis of trace elements on biomedical samples, in vitro and in vivo, by XRF-analysis; the ability of the PIXE-microprobe to analyze in detail and tomore » map trace elements in fragments of biomedical samples or inside the cells; the potentiality of in vivo nuclear activation analysis for diagnostic purposes. Finally, techniques are described such as radiation scattering (elastic and inelastic scattering) and attenuation measurements which will undoubtedly see great development in the immediate future.« less

Reconstructing genome-wide regulatory network of E. coli using transcriptome data and predicted transcription factor activities

PubMed Central

2011-01-01

Background Gene regulatory networks play essential roles in living organisms to control growth, keep internal metabolism running and respond to external environmental changes. Understanding the connections and the activity levels of regulators is important for the research of gene regulatory networks. While relevance score based algorithms that reconstruct gene regulatory networks from transcriptome data can infer genome-wide gene regulatory networks, they are unfortunately prone to false positive results. Transcription factor activities (TFAs) quantitatively reflect the ability of the transcription factor to regulate target genes. However, classic relevance score based gene regulatory network reconstruction algorithms use models do not include the TFA layer, thus missing a key regulatory element. Results This work integrates TFA prediction algorithms with relevance score based network reconstruction algorithms to reconstruct gene regulatory networks with improved accuracy over classic relevance score based algorithms. This method is called Gene expression and Transcription factor activity based Relevance Network (GTRNetwork). Different combinations of TFA prediction algorithms and relevance score functions have been applied to find the most efficient combination. When the integrated GTRNetwork method was applied to E. coli data, the reconstructed genome-wide gene regulatory network predicted 381 new regulatory links. This reconstructed gene regulatory network including the predicted new regulatory links show promising biological significances. Many of the new links are verified by known TF binding site information, and many other links can be verified from the literature and databases such as EcoCyc. The reconstructed gene regulatory network is applied to a recent transcriptome analysis of E. coli during isobutanol stress. In addition to the 16 significantly changed TFAs detected in the original paper, another 7 significantly changed TFAs have been detected by using our reconstructed network. Conclusions The GTRNetwork algorithm introduces the hidden layer TFA into classic relevance score-based gene regulatory network reconstruction processes. Integrating the TFA biological information with regulatory network reconstruction algorithms significantly improves both detection of new links and reduces that rate of false positives. The application of GTRNetwork on E. coli gene transcriptome data gives a set of potential regulatory links with promising biological significance for isobutanol stress and other conditions. PMID:21668997

Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease*

PubMed Central

Dewhurst, Henry; Sundararaman, Niveda

2016-01-01

Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable body of potential regulatory elements that impact hundreds of different biological processes important in eukaryotic biology and human health. PMID:27697855

Designing synthetic RNAs to determine the relevance of structural motifs in picornavirus IRES elements

NASA Astrophysics Data System (ADS)

Fernandez-Chamorro, Javier; Lozano, Gloria; Garcia-Martin, Juan Antonio; Ramajo, Jorge; Dotu, Ivan; Clote, Peter; Martinez-Salas, Encarnacion

2016-04-01

The function of Internal Ribosome Entry Site (IRES) elements is intimately linked to their RNA structure. Viral IRES elements are organized in modular domains consisting of one or more stem-loops that harbor conserved RNA motifs critical for internal initiation of translation. A conserved motif is the pyrimidine-tract located upstream of the functional initiation codon in type I and II picornavirus IRES. By computationally designing synthetic RNAs to fold into a structure that sequesters the polypyrimidine tract in a hairpin, we establish a correlation between predicted inaccessibility of the pyrimidine tract and IRES activity, as determined in both in vitro and in vivo systems. Our data supports the hypothesis that structural sequestration of the pyrimidine-tract within a stable hairpin inactivates IRES activity, since the stronger the stability of the hairpin the higher the inhibition of protein synthesis. Destabilization of the stem-loop immediately upstream of the pyrimidine-tract also decreases IRES activity. Our work introduces a hybrid computational/experimental method to determine the importance of structural motifs for biological function. Specifically, we show the feasibility of using the software RNAiFold to design synthetic RNAs with particular sequence and structural motifs that permit subsequent experimental determination of the importance of such motifs for biological function.

Mechano-biological Coupling of Cellular Responses to Microgravity

NASA Astrophysics Data System (ADS)

Long, Mian; Wang, Yuren; Zheng, Huiqiong; Shang, Peng; Duan, Enkui; Lü, Dongyuan

2015-11-01

Cellular response to microgravity is a basic issue in space biological sciences as well as space physiology and medicine. It is crucial to elucidate the mechano-biological coupling mechanisms of various biological organisms, since, from the principle of adaptability, all species evolved on the earth must possess the structure and function that adapts their living environment. As a basic element of an organism, a cell usually undergoes mechanical and chemical remodeling to sense, transmit, transduce, and respond to the alteration of gravitational signals. In the past decades, new computational platforms and experimental methods/techniques/devices are developed to mimic the biological effects of microgravity environment from the viewpoint of biomechanical approaches. Mechanobiology of plant gravisensing in the responses of statolith movements along the gravity vector and the relevant signal transduction and molecular regulatory mechanisms are investigated at gene, transcription, and protein levels. Mechanotransduction of bone or immune cell responses and stem cell development and tissue histogenesis are elucidated under microgravity. In this review, several important issues are briefly discussed. Future issues on gravisensing and mechanotransducing mechanisms are also proposed for ground-based studies as well as space missions.

BioModels Database: a repository of mathematical models of biological processes.

PubMed

Chelliah, Vijayalakshmi; Laibe, Camille; Le Novère, Nicolas

2013-01-01

BioModels Database is a public online resource that allows storing and sharing of published, peer-reviewed quantitative, dynamic models of biological processes. The model components and behaviour are thoroughly checked to correspond the original publication and manually curated to ensure reliability. Furthermore, the model elements are annotated with terms from controlled vocabularies as well as linked to relevant external data resources. This greatly helps in model interpretation and reuse. Models are stored in SBML format, accepted in SBML and CellML formats, and are available for download in various other common formats such as BioPAX, Octave, SciLab, VCML, XPP and PDF, in addition to SBML. The reaction network diagram of the models is also available in several formats. BioModels Database features a search engine, which provides simple and more advanced searches. Features such as online simulation and creation of smaller models (submodels) from the selected model elements of a larger one are provided. BioModels Database can be accessed both via a web interface and programmatically via web services. New models are available in BioModels Database at regular releases, about every 4 months.

Evidence of pervasive biologically functional secondary structures within the genomes of eukaryotic single-stranded DNA viruses.

PubMed

Muhire, Brejnev Muhizi; Golden, Michael; Murrell, Ben; Lefeuvre, Pierre; Lett, Jean-Michel; Gray, Alistair; Poon, Art Y F; Ngandu, Nobubelo Kwanele; Semegni, Yves; Tanov, Emil Pavlov; Monjane, Adérito Luis; Harkins, Gordon William; Varsani, Arvind; Shepherd, Dionne Natalie; Martin, Darren Patrick

2014-02-01

Single-stranded DNA (ssDNA) viruses have genomes that are potentially capable of forming complex secondary structures through Watson-Crick base pairing between their constituent nucleotides. A few of the structural elements formed by such base pairings are, in fact, known to have important functions during the replication of many ssDNA viruses. Unknown, however, are (i) whether numerous additional ssDNA virus genomic structural elements predicted to exist by computational DNA folding methods actually exist and (ii) whether those structures that do exist have any biological relevance. We therefore computationally inferred lists of the most evolutionarily conserved structures within a diverse selection of animal- and plant-infecting ssDNA viruses drawn from the families Circoviridae, Anelloviridae, Parvoviridae, Nanoviridae, and Geminiviridae and analyzed these for evidence of natural selection favoring the maintenance of these structures. While we find evidence that is consistent with purifying selection being stronger at nucleotide sites that are predicted to be base paired than at sites predicted to be unpaired, we also find strong associations between sites that are predicted to pair with one another and site pairs that are apparently coevolving in a complementary fashion. Collectively, these results indicate that natural selection actively preserves much of the pervasive secondary structure that is evident within eukaryote-infecting ssDNA virus genomes and, therefore, that much of this structure is biologically functional. Lastly, we provide examples of various highly conserved but completely uncharacterized structural elements that likely have important functions within some of the ssDNA virus genomes analyzed here.

Evidence of Pervasive Biologically Functional Secondary Structures within the Genomes of Eukaryotic Single-Stranded DNA Viruses

PubMed Central

Muhire, Brejnev Muhizi; Golden, Michael; Murrell, Ben; Lefeuvre, Pierre; Lett, Jean-Michel; Gray, Alistair; Poon, Art Y. F.; Ngandu, Nobubelo Kwanele; Semegni, Yves; Tanov, Emil Pavlov; Monjane, Adérito Luis; Harkins, Gordon William; Varsani, Arvind; Shepherd, Dionne Natalie

2014-01-01

Single-stranded DNA (ssDNA) viruses have genomes that are potentially capable of forming complex secondary structures through Watson-Crick base pairing between their constituent nucleotides. A few of the structural elements formed by such base pairings are, in fact, known to have important functions during the replication of many ssDNA viruses. Unknown, however, are (i) whether numerous additional ssDNA virus genomic structural elements predicted to exist by computational DNA folding methods actually exist and (ii) whether those structures that do exist have any biological relevance. We therefore computationally inferred lists of the most evolutionarily conserved structures within a diverse selection of animal- and plant-infecting ssDNA viruses drawn from the families Circoviridae, Anelloviridae, Parvoviridae, Nanoviridae, and Geminiviridae and analyzed these for evidence of natural selection favoring the maintenance of these structures. While we find evidence that is consistent with purifying selection being stronger at nucleotide sites that are predicted to be base paired than at sites predicted to be unpaired, we also find strong associations between sites that are predicted to pair with one another and site pairs that are apparently coevolving in a complementary fashion. Collectively, these results indicate that natural selection actively preserves much of the pervasive secondary structure that is evident within eukaryote-infecting ssDNA virus genomes and, therefore, that much of this structure is biologically functional. Lastly, we provide examples of various highly conserved but completely uncharacterized structural elements that likely have important functions within some of the ssDNA virus genomes analyzed here. PMID:24284329

DNA sequencing methods in human genetics and disease research

PubMed Central

2013-01-01

DNA sequencing has revolutionized biological and medical research, and is poised to have a similar impact in medicine. This tool is just one of a number of developments in our capability to identify, quantitate and functionally characterize the components of the biological networks keeping us healthy or making us sick, but in many respects it has played the leading role in this process. The new technologies do, however, also provide a bridge between genotype and phenotype, both in man and model (as well as all other) organisms, revolutionize the identification of elements involved in a multitude of human diseases or other phenotypes, and generate a wealth of medically relevant information on every single person, as the basis of a truly personalized medicine of the future. PMID:24049638

The Metals in the Biological Periodic System of the Elements: Concepts and Conjectures

PubMed Central

Maret, Wolfgang

2016-01-01

A significant number of chemical elements are either essential for life with known functions, or present in organisms with poorly defined functional outcomes. We do not know all the essential elements with certainty and we know even less about the functions of apparently non-essential elements. In this article, I discuss a basis for a biological periodic system of the elements and that biochemistry should include the elements that are traditionally part of inorganic chemistry and not only those that are in the purview of organic chemistry. A biological periodic system of the elements needs to specify what “essential” means and to which biological species it refers. It represents a snapshot of our present knowledge and is expected to undergo further modifications in the future. An integrated approach of biometal sciences called metallomics is required to understand the interactions of metal ions, the biological functions that their chemical structures acquire in the biological system, and how their usage is fine-tuned in biological species and in populations of species with genetic variations (the variome). PMID:26742035

Trichomonas vaginalis ribosomal RNA: identification and characterisation of the transcription promoter and terminator sequences.

PubMed

Franco, Bernardo; Hernández, Roberto; López-Villaseñor, Imelda

2012-09-01

Trichomonas vaginalis is a parasitic protozoan of both medical and biological relevance. Transcriptional studies in this organism have focused mainly on type II pol promoters, whereas the elements necessary for transcription by polI or polIII have not been investigated. Here, with the aid of a transient transcription system, we characterised the rDNA intergenic region, defining both the promoter and the terminator sequences required for transcription. We defined the promoter as a compact region of approximately 180 bp. We also identified a potential upstream control element (UCE) that was located 80 bp upstream of the transcription start point (TSP). A transcription termination element was identified within a 34 bp region that was located immediately downstream of the 28S coding sequence. The function of this element depends upon polarity and the presence of both a stretch of uridine residues (U's) and a hairpin structure in the transcript. Our observations provide a strong basis for the study of DNA recognition by the polI transcriptional machinery in this early divergent organism. Copyright © 2012 Elsevier B.V. All rights reserved.

Bio-metals imaging and speciation in cells using proton and synchrotron radiation X-ray microspectroscopy

PubMed Central

Ortega, Richard; Devès, Guillaume; Carmona, Asunción

2009-01-01

The direct detection of biologically relevant metals in single cells and of their speciation is a challenging task that requires sophisticated analytical developments. The aim of this article is to present the recent achievements in the field of cellular chemical element imaging, and direct speciation analysis, using proton and synchrotron radiation X-ray micro- and nano-analysis. The recent improvements in focusing optics for MeV-accelerated particles and keV X-rays allow application to chemical element analysis in subcellular compartments. The imaging and quantification of trace elements in single cells can be obtained using particle-induced X-ray emission (PIXE). The combination of PIXE with backscattering spectrometry and scanning transmission ion microscopy provides a high accuracy in elemental quantification of cellular organelles. On the other hand, synchrotron radiation X-ray fluorescence provides chemical element imaging with less than 100 nm spatial resolution. Moreover, synchrotron radiation offers the unique capability of spatially resolved chemical speciation using micro-X-ray absorption spectroscopy. The potential of these methods in biomedical investigations will be illustrated with examples of application in the fields of cellular toxicology, and pharmacology, bio-metals and metal-based nano-particles. PMID:19605403

Comparison of the perceived relevance of oral biology reported by students and interns of a Pakistani dental college.

PubMed

Farooq, I; Ali, S

2014-11-01

The purpose of this study was to analyse and compare the perceived relevance of oral biology with dentistry as reported by dental students and interns and to investigate the most popular teaching approach and learning resource. A questionnaire aiming to ask about the relevance of oral biology to dentistry, most popular teaching method and learning resource was utilised in this study. Study groups encompassed second-year dental students who had completed their course and dental interns. The data were obtained and analysed statistically. The overall response rate for both groups was 60%. Both groups reported high relevance of oral biology to dentistry. Perception of dental interns regarding the relevance of oral biology to dentistry was higher than that of students. Both groups identified student presentations as the most important teaching method. Amongst the most important learning resources, textbooks were considered most imperative by interns, whereas lecture handouts received the highest importance score by students. Dental students and interns considered oral biology to be relevant to dentistry, although greater relevance was reported by interns. Year-wise advancement in dental education and training improves the perception of the students about the relevance of oral biology to dentistry. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Composition of commercial media used for human embryo culture.

PubMed

Morbeck, Dean E; Krisher, Rebecca L; Herrick, Jason R; Baumann, Nikola A; Matern, Dietrich; Moyer, Thomas

2014-09-01

To determine the composition of commercially available culture media and test whether differences in composition are biologically relevant in a murine model. Experimental laboratory study. University-based laboratory. Cryopreserved hybrid mouse one-cell embryos were used in experiments. Amino acid, organic acid, ions, and metal content were determined for two different lots of media from Cook, In Vitro Care, Origio, Sage, Vitrolife, Irvine CSC, and Global. To determine whether differences in the composition of these media are biologically relevant, mouse one-cell embryos were thawed and cultured for 120 hours in each culture media at 5% and 20% oxygen in the presence or absence of protein in an EmbryoScope time-lapse incubator. The compositions of seven culture media were analyzed for concentrations of 39 individual amino acids, organic acids, ions, and elements. Blastocyst rates and cell cycle timings were calculated at 96 hours of culture, and the experiments were repeated in triplicate. Of the 39 analytes, concentrations of glucose, lactate, pyruvate, amino acids, phosphate, calcium, and magnesium were present in variable concentrations, likely reflecting differences in the interpretation of animal studies. Essential trace elements, such as copper and zinc, were not detected. Mouse embryos failed to develop in one culture medium and were differentially affected by oxygen in two other media. Culture media composition varies widely, with differences in pyruvate, lactate, and amino acids especially notable. Blastocyst development was culture media dependent and showed an interaction with oxygen concentration and presence of protein. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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 relevance. The results of this study will inform instructors' pedagogical and logistical choices in the design and implementation of higher education biology courses for non-biology majors. Recommendations for future research will include refining the study to train instructors in methods of instruction that promote student engagement as well as to identify biology topics that are more relevant to students enrolled in non-major biology courses.

Unzippers, Resolvers and Sensors: A Structural and Functional Biochemistry Tale of RNA Helicases

PubMed Central

Leitão, Ana Lúcia; Costa, Marina C.; Enguita, Francisco J.

2015-01-01

The centrality of RNA within the biological world is an irrefutable fact that currently attracts increasing attention from the scientific community. The panoply of functional RNAs requires the existence of specific biological caretakers, RNA helicases, devoted to maintain the proper folding of those molecules, resolving unstable structures. However, evolution has taken advantage of the specific position and characteristics of RNA helicases to develop new functions for these proteins, which are at the interface of the basic processes for transference of information from DNA to proteins. RNA helicases are involved in many biologically relevant processes, not only as RNA chaperones, but also as signal transducers, scaffolds of molecular complexes, and regulatory elements. Structural biology studies during the last decade, founded in X-ray crystallography, have characterized in detail several RNA-helicases. This comprehensive review summarizes the structural knowledge accumulated in the last two decades within this family of proteins, with special emphasis on the structure-function relationships of the most widely-studied families of RNA helicases: the DEAD-box, RIG-I-like and viral NS3 classes. PMID:25622248

A Strategy to Safely Live and Work in the Space Radiation Environment

NASA Technical Reports Server (NTRS)

Corbin, Barbara J.; Sulzman, Frank M.; Krenek, Sam

2006-01-01

The goal of the National Aeronautics and Space Agency and the Space Radiation Project is to ensure that astronauts can safely live and work in the space radiation environment. The space radiation environment poses both acute and chronic risks to crew health and safety, but unlike some other aspects of space travel, space radiation exposure has clinically relevant implications for the lifetime of the crew. The term safely means that risks are sufficiently understood such that acceptable limits on mission, post-mission and multi-mission consequences (for example, excess lifetime fatal cancer risk) can be defined. The Space Radiation Project strategy has several elements. The first element is to use a peer-reviewed research program to increase our mechanistic knowledge and genetic capabilities to develop tools for individual risk projection, thereby reducing our dependency on epidemiological data and population-based risk assessment. The second element is to use the NASA Space Radiation Laboratory to provide a ground-based facility to study the understanding of health effects/mechanisms of damage from space radiation exposure and the development and validation of biological models of risk, as well as methods for extrapolation to human risk. The third element is a risk modeling effort that integrates the results from research efforts into models of human risk to reduce uncertainties in predicting risk of carcinogenesis, central nervous system damage, degenerative tissue disease, and acute radiation effects. To understand the biological basis for risk, we must also understand the physical aspects of the crew environment. Thus the fourth element develops computer codes to predict radiation transport properties, evaluate integrated shielding technologies and provide design optimization recommendations for the design of human space systems. Understanding the risks and determining methods to mitigate the risks are keys to a successful radiation protection strategy.

Bioaccessibility studies of ferro-chromium alloy particles for a simulated inhalation scenario: a comparative study with the pure metals and stainless steel.

PubMed

Midander, Klara; de Frutos, Alfredo; Hedberg, Yolanda; Darrie, Grant; Wallinder, Inger Odnevall

2010-07-01

The European product safety legislation, REACH, requires that companies that manufacture, import, or use chemicals demonstrate safe use and high level of protection of their products placed on the market from a human health and environmental perspective. This process involves detailed assessment of potential hazards for various toxicity endpoints induced by the use of chemicals with a minimum use of animal testing. Such an assessment requires thorough understanding of relevant exposure scenarios including material characteristics and intrinsic properties and how, for instance, physical and chemical properties change from the manufacturing phase, throughout use, to final disposal. Temporary or permanent adverse health effects induced by particles depend either on their shape or physical characteristics, and/or on chemical interactions with the particle surface upon human exposure. Potential adverse effects caused by the exposure of metal particles through the gastrointestinal system, the pulmonary system, or the skin, and their subsequent potential for particle dissolution and metal release in contact with biological media, show significant gaps of knowledge. In vitro bioaccessibility testing at conditions of relevance for different exposure scenarios, combined with the generation of a detailed understanding of intrinsic material properties and surface characteristics, are in this context a useful approach to address aspects of relevance for accurate risk and hazard assessment of chemicals, including metals and alloys and to avoid the use of in vivo testing. Alloys are essential engineering materials in all kinds of applications in society, but their potential adverse effects on human health and the environment are very seldom assessed. Alloys are treated in REACH as mixtures of their constituent elements, an approach highly inappropriate because intrinsic properties of alloys generally are totally different compared with their pure metal components. A large research effort was therefore conducted to generate quantitative bioaccessibility data for particles of ferro-chromium alloys compared with particles of the pure metals and stainless steel exposed at in vitro conditions in synthetic biological media of relevance for particle inhalation and ingestion. All results are presented combining bioaccessibility data with aspects of particle characteristics, surface composition, and barrier properties of surface oxides. Iron and chromium were the main elements released from ferro-chromium alloys upon exposure in synthetic biological media. Both elements revealed time-dependent release processes. One week exposures resulted in very small released particle fractions being less than 0.3% of the particle mass at acidic conditions and less than 0.001% in near pH-neutral media. The extent of Fe released from ferro-chromium alloy particles was significantly lower compared with particles of pure Fe, whereas Cr was released to a very low and similar extent as from particles of pure Cr and stainless steel. Low release rates are a result of a surface oxide with passive properties predominantly composed of chromium(III)-rich oxides and silica and, to a lesser extent, of iron(II,III)oxides. Neither the relative bulk alloy composition nor the surface composition can be used to predict or assess the extent of metals released in different synthetic biological media. Ferro-chromium alloys cannot be assessed from the behavior of their pure metal constituents. (c) 2009 SETAC.

Taxonomic indexing--extending the role of taxonomy.

PubMed

Patterson, David J; Remsen, David; Marino, William A; Norton, Cathy

2006-06-01

Taxonomic indexing refers to a new array of taxonomically intelligent network services that use nomenclatural principles and elements of expert taxonomic knowledge to manage information about organisms. Taxonomic indexing was introduced to help manage the increasing amounts of digital information about biology. It has been designed to form a near basal layer in a layered cyberinfrastructure that deals with biological information. Taxonomic Indexing accommodates the special problems of using names of organisms to index biological material. It links alternative names for the same entity (reconciliation), and distinguishes between uses of the same name for different entities (disambiguation), and names are placed within an indefinite number of hierarchical schemes. In order to access all information on all organisms, Taxonomic indexing must be able to call on a registry of all names in all forms for all organisms. NameBank has been developed to meet that need. Taxonomic indexing is an area of informatics that overlaps with taxonomy, is dependent on the expert input of taxonomists, and reveals the relevance of the discipline to a wide audience.

The Mediator Complex and Lipid Metabolism.

PubMed

Zhang, Yi; Xiaoli; Zhao, Xiaoping; Yang, Fajun

2013-03-01

The precise control of gene expression is essential for all biological processes. In addition to DNA-binding transcription factors, numerous transcription cofactors contribute another layer of regulation of gene transcription in eukaryotic cells. One of such transcription cofactors is the highly conserved Mediator complex, which has multiple subunits and is involved in various biological processes through directly interacting with relevant transcription factors. Although the current understanding on the biological functions of Mediator remains incomplete, research in the past decade has revealed an important role of Mediator in regulating lipid metabolism. Such function of Mediator is dependent on specific transcription factors, including peroxisome proliferator-activated receptor-gamma (PPARγ) and sterol regulatory element-binding proteins (SREBPs), which represent the master regulators of lipid metabolism. The medical significance of these findings is apparent, as aberrant lipid metabolism is intimately linked to major human diseases, such as type 2 diabetes and cardiovascular disease. Here, we briefly review the functions and molecular mechanisms of Mediator in regulation of lipid metabolism.

Nestedness across biological scales

PubMed Central

Marquitti, Flavia M. D.; Raimundo, Rafael L. G.; Sebastián-González, Esther; Coltri, Patricia P.; Perez, S. Ivan; Brandt, Débora Y. C.; Nunes, Kelly; Daura-Jorge, Fábio G.; Floeter, Sergio R.; Guimarães, Paulo R.

2017-01-01

Biological networks pervade nature. They describe systems throughout all levels of biological organization, from molecules regulating metabolism to species interactions that shape ecosystem dynamics. The network thinking revealed recurrent organizational patterns in complex biological systems, such as the formation of semi-independent groups of connected elements (modularity) and non-random distributions of interactions among elements. Other structural patterns, such as nestedness, have been primarily assessed in ecological networks formed by two non-overlapping sets of elements; information on its occurrence on other levels of organization is lacking. Nestedness occurs when interactions of less connected elements form proper subsets of the interactions of more connected elements. Only recently these properties began to be appreciated in one-mode networks (where all elements can interact) which describe a much wider variety of biological phenomena. Here, we compute nestedness in a diverse collection of one-mode networked systems from six different levels of biological organization depicting gene and protein interactions, complex phenotypes, animal societies, metapopulations, food webs and vertebrate metacommunities. Our findings suggest that nestedness emerge independently of interaction type or biological scale and reveal that disparate systems can share nested organization features characterized by inclusive subsets of interacting elements with decreasing connectedness. We primarily explore the implications of a nested structure for each of these studied systems, then theorize on how nested networks are assembled. We hypothesize that nestedness emerges across scales due to processes that, although system-dependent, may share a general compromise between two features: specificity (the number of interactions the elements of the system can have) and affinity (how these elements can be connected to each other). Our findings suggesting occurrence of nestedness throughout biological scales can stimulate the debate on how pervasive nestedness may be in nature, while the theoretical emergent principles can aid further research on commonalities of biological networks. PMID:28166284

Participation of Xenopus Elr-type Proteins in Vegetal mRNA Localization during Oogenesis*

PubMed Central

Arthur, Patrick K.; Claussen, Maike; Koch, Susanne; Tarbashevich, Katsiaryna; Jahn, Olaf; Pieler, Tomas

2009-01-01

Directional transport of specific mRNAs is of primary biological relevance. In Xenopus oocytes, mRNA localization to the vegetal pole is important for germ layer formation and germ cell development. Using a biochemical approach, we identified Xenopus Elr-type proteins, homologs of the Hu/ELAV proteins, as novel components of the vegetal mRNA localization machinery. They bind specifically to the localization elements of several different vegetally localizing Xenopus mRNAs, and they are part of one RNP together with other localization proteins, such as Vg1RBP and XStaufen 1. Blocking Elr-type protein binding by either localization element mutagenesis or antisense morpholino oligonucleotide-mediated masking of their target RNA structures, as well as overexpression of wild type and mutant ElrB proteins, interferes with vegetal localization in Xenopus oocytes. PMID:19458392

The C-terminal Helix of Pseudomonas aeruginosa Elongation Factor Ts Tunes EF-Tu Dynamics to Modulate Nucleotide Exchange.

PubMed

De Laurentiis, Evelina Ines; Mercier, Evan; Wieden, Hans-Joachim

2016-10-28

Little is known about the conservation of critical kinetic parameters and the mechanistic strategies of elongation factor (EF) Ts-catalyzed nucleotide exchange in EF-Tu in bacteria and particularly in clinically relevant pathogens. EF-Tu from the clinically relevant pathogen Pseudomonas aeruginosa shares over 84% sequence identity with the corresponding elongation factor from Escherichia coli Interestingly, the functionally closely linked EF-Ts only shares 55% sequence identity. To identify any differences in the nucleotide binding properties, as well as in the EF-Ts-mediated nucleotide exchange reaction, we performed a comparative rapid kinetics and mutagenesis analysis of the nucleotide exchange mechanism for both the E. coli and P. aeruginosa systems, identifying helix 13 of EF-Ts as a previously unnoticed regulatory element in the nucleotide exchange mechanism with species-specific elements. Our findings support the base side-first entry of the nucleotide into the binding pocket of the EF-Tu·EF-Ts binary complex, followed by displacement of helix 13 and rapid binding of the phosphate side of the nucleotide, ultimately leading to the release of EF-Ts. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Thickness of Weathering Profiles:Relaying Tectonic Signal to Biogeochemical Cycles

NASA Astrophysics Data System (ADS)

Yoo, K.; Weinman, B. A.; Hurst, M. D.; Mudd, S. M.; Gabet, E. J.; Attal, M.; Maher, K.

2011-12-01

Generation and transport of sediment across hillslopes and rivers are closely tied to mechanisms that produce and remove weathered material; in uplands this production and transport controls the thicknesses of weathering profiles. These processes, by controlling the residence time of minerals in the weathering profiles, further regulate the interactions between these minerals and largely biologically cycled elements like carbon and calcium. Here, we present and discuss the thicknesses of colluvial soils and underlying saprolites along three hillslopes that are subject to different rates of basal channel incision. Our field site is within a tributary basin to the Middle Folk Feather River in the Northern Sierra Nevada of California where the river has been down cutting through an uplifting granitic batholith over the past five to ten million years. Conventional modeling predicts that colluvial soil thickness declines with increasing denudation rates. Contrary to this expectation, intensive measurements of colluvial soil thickness show largely consistent values across the three hillslopes examined. This finding, in combination with the abrupt transitions to partial or full bare-rock landscapes with further increase in slope curvature or greater proximity to the Middle Folk Feather River, suggests that the mechanisms of soil production are capable of keeping pace with physical erosion rate until a certain threshold erosion rate is reached. We observe, however, that thicknesses of the underlying saprolite and the morphology (eg., color and texture) and geochemistry (eg., elemental concentration and extraction chemistry of iron) of both colluvial soil and saprolite materials vary systematically with the total denudation rates. This finding further allows us to build a simple relationship to describe and predict how the changes in erosion rates translate to the soils' capacity to store biologically cycled elements within rooting depths. Therefore, geomorphic and geochemical processes that control the thicknesses of weathering profiles, by determining their turn over time as well, relay the tectonic signal to the cycles of biologically relevant elements.

Silk-polypyrrole biocompatible actuator performance under biologically relevant conditions

NASA Astrophysics Data System (ADS)

Hagler, Jo'elen; Peterson, Ben; Murphy, Amanda; Leger, Janelle

Biocompatible actuators that are capable of controlled movement and can function under biologically relevant conditions are of significant interest in biomedical fields. Previously, we have demonstrated that a composite material of silk biopolymer and the conducting polymer polypyrrole (PPy) can be formed into a bilayer device that can bend under applied voltage. Further, these silk-PPy composites can generate forces comparable to human muscle (>0.1 MPa) making them ideal candidates for interfacing with biological tissues. Here silk-PPy composite films are tested for performance under biologically relevant conditions including exposure to a complex protein serum and biologically relevant temperatures. Free-end bending actuation performance, current response, force generation and, mass degradation were investigated . Preliminary results show that when exposed to proteins and biologically relevant temperatures, these silk-PPy composites show minimal degradation and are able to generate forces and conduct currents comparable to devices tested under standard conditions. NSF.

Quantitative assessment of submicron scale anisotropy in tissue multifractality by scattering Mueller matrix in the framework of Born approximation

NASA Astrophysics Data System (ADS)

Das, Nandan Kumar; Dey, Rajib; Chakraborty, Semanti; Panigrahi, Prasanta K.; Meglinski, Igor; Ghosh, Nirmalya

2018-04-01

A number of tissue-like disordered media exhibit local anisotropy of scattering in the scaling behavior. Scaling behavior contains wealth of fractal or multifractal properties. We demonstrate that the spatial dielectric fluctuations in a sample of biological tissue exhibit multifractal anisotropy. Multifractal anisotropy encoded in the wavelength variation of the light scattering Mueller matrix and manifesting as an intriguing spectral diattenuation effect. We developed an inverse method for the quantitative assessment of the multifractal anisotropy. The method is based on the processing of relevant Mueller matrix elements in Fourier domain by using Born approximation, followed by the multifractal analysis. The approach promises for probing subtle micro-structural changes in biological tissues associated with the cancer and precancer, as well as for non-destructive characterization of a wide range of scattering materials.

Analysis of diffusion in curved surfaces and its application to tubular membranes

PubMed Central

Klaus, Colin James Stockdale; Raghunathan, Krishnan; DiBenedetto, Emmanuele; Kenworthy, Anne K.

2016-01-01

Diffusion of particles in curved surfaces is inherently complex compared with diffusion in a flat membrane, owing to the nonplanarity of the surface. The consequence of such nonplanar geometry on diffusion is poorly understood but is highly relevant in the case of cell membranes, which often adopt complex geometries. To address this question, we developed a new finite element approach to model diffusion on curved membrane surfaces based on solutions to Fick’s law of diffusion and used this to study the effects of geometry on the entry of surface-bound particles into tubules by diffusion. We show that variations in tubule radius and length can distinctly alter diffusion gradients in tubules over biologically relevant timescales. In addition, we show that tubular structures tend to retain concentration gradients for a longer time compared with a comparable flat surface. These findings indicate that sorting of particles along the surfaces of tubules can arise simply as a geometric consequence of the curvature without any specific contribution from the membrane environment. Our studies provide a framework for modeling diffusion in curved surfaces and suggest that biological regulation can emerge purely from membrane geometry. PMID:27733625

Biological ageing and clinical consequences of modern technology.

PubMed

Kyriazis, Marios

2017-08-01

The pace of technology is steadily increasing, and this has a widespread effect on all areas of health and society. When we interact with this technological environment we are exposed to a wide variety of new stimuli and challenges, which may modulate the stress response and thus change the way we respond and adapt. In this Opinion paper I will examine certain aspects of the human-computer interaction with regards to health and ageing. There are practical, everyday effects which also include social and cultural elements. I will discuss how human evolution may be affected by this new environmental change (the hormetic immersion in a virtual/technological environment). Finally, I will also explore certain biological aspects which have direct relevance to the ageing human. By embracing new technologies and engaging with a techno-social ecosystem (which is no longer formed by several interacting species, but by just two main elements: humans and machines), we may be subjected to beneficial hormetic effects, which upregulate the stress response and modulate adaptation. This is likely to improve overall health as we age and, as I speculate here, may also result in the reduction of age-related dysfunction.

Feasibility of an integrated X-ray instrument for Mars exobiology and geology. [Abstract only

NASA Technical Reports Server (NTRS)

Fonda, M. L.; Schwartz, D. E.; Koppel, L. N.; Franco, E. D.; Kerner, J. A.

1994-01-01

By employing an integrated X-ray instrument on a future Mars mission, data obtained will greatly augment those returned by Viking; details relevant to the possibility of the origin and evolution of life on Mars will be acquired. An integrated combined X Ray Fluorescence/X Ray Detection (XRF/XRD) instrument has been breadboarded and demonstrated to accommodate important exobiology and geology experiment objectives outlined for Mars Environmental Survey (MESUR) and future Mars missions. Among others, primary objectives for the exploration of Mars include: the intense study of local areas on Mars to 'establish the chemical, mineralogical, and petrological character of different components of the surface material; to determine the distribution, abundance and sources and sinks of volatile materials, including an assessment of the biologic potential, now and during past epochs; and to establish the global chemical and physical characteristics of the Martian surface'. The XRF/XRD breadboard instrument identifies and quantifies soil surface elemental, mineralogical, and petrological characteristics and acquires data necessary to address questions on volatile abundance and distribution. Additionally, the breadboard is able to characterize the biogenic element constituents of soil samples providing information on the biologic potential of the Mars environment.

Dehomogenized Elastic Properties of Heterogeneous Layered Materials in AFM Indentation Experiments.

PubMed

Lee, Jia-Jye; Rao, Satish; Kaushik, Gaurav; Azeloglu, Evren U; Costa, Kevin D

2018-06-05

Atomic force microscopy (AFM) is used to study mechanical properties of biological materials at submicron length scales. However, such samples are often structurally heterogeneous even at the local level, with different regions having distinct mechanical properties. Physical or chemical disruption can isolate individual structural elements but may alter the properties being measured. Therefore, to determine the micromechanical properties of intact heterogeneous multilayered samples indented by AFM, we propose the Hybrid Eshelby Decomposition (HED) analysis, which combines a modified homogenization theory and finite element modeling to extract layer-specific elastic moduli of composite structures from single indentations, utilizing knowledge of the component distribution to achieve solution uniqueness. Using finite element model-simulated indentation of layered samples with micron-scale thickness dimensions, biologically relevant elastic properties for incompressible soft tissues, and layer-specific heterogeneity of an order of magnitude or less, HED analysis recovered the prescribed modulus values typically within 10% error. Experimental validation using bilayer spin-coated polydimethylsiloxane samples also yielded self-consistent layer-specific modulus values whether arranged as stiff layer on soft substrate or soft layer on stiff substrate. We further examined a biophysical application by characterizing layer-specific microelastic properties of full-thickness mouse aortic wall tissue, demonstrating that the HED-extracted modulus of the tunica media was more than fivefold stiffer than the intima and not significantly different from direct indentation of exposed media tissue. Our results show that the elastic properties of surface and subsurface layers of microscale synthetic and biological samples can be simultaneously extracted from the composite material response to AFM indentation. HED analysis offers a robust approach to studying regional micromechanics of heterogeneous multilayered samples without destructively separating individual components before testing. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Chemical warfare in termites.

PubMed

Sobotník, Jan; Jirosová, Anna; Hanus, Robert

2010-09-01

The rapid development of analytical methods in the last four decades has led to the discovery of a fascinating diversity of defensive chemicals used by termites. The last exhaustive review on termite defensive chemicals was published by G.D. Prestwich in 1984. In this text, we aim to fill the gap of the past 25 years and overview all of the relevant primary sources about the chemistry of termite defense (126 original papers, see Fig. 1 and online supplementary material) along with related biological aspects, such as the anatomy of defensive glands and their functional mechanisms, alarm communication, and the evolutionary significance of these defensive elements.

Attraction of posture and motion-trajectory elements of conspecific biological motion in medaka fish.

PubMed

Shibai, Atsushi; Arimoto, Tsunehiro; Yoshinaga, Tsukasa; Tsuchizawa, Yuta; Khureltulga, Dashdavaa; Brown, Zuben P; Kakizuka, Taishi; Hosoda, Kazufumi

2018-06-05

Visual recognition of conspecifics is necessary for a wide range of social behaviours in many animals. Medaka (Japanese rice fish), a commonly used model organism, are known to be attracted by the biological motion of conspecifics. However, biological motion is a composite of both body-shape motion and entire-field motion trajectory (i.e., posture or motion-trajectory elements, respectively), and it has not been revealed which element mediates the attractiveness. Here, we show that either posture or motion-trajectory elements alone can attract medaka. We decomposed biological motion of the medaka into the two elements and synthesized visual stimuli that contain both, either, or none of the two elements. We found that medaka were attracted by visual stimuli that contain at least one of the two elements. In the context of other known static visual information regarding the medaka, the potential multiplicity of information regarding conspecific recognition has further accumulated. Our strategy of decomposing biological motion into these partial elements is applicable to other animals, and further studies using this technique will enhance the basic understanding of visual recognition of conspecifics.

A Global Overview of Exposure Levels and Biological Effects of Trace Elements in Penguins.

PubMed

Espejo, Winfred; Celis, José E; GonzÃlez-Acuña, Daniel; Banegas, Andiranel; Barra, Ricardo; Chiang, Gustavo

2018-01-01

Trace elements are chemical contaminants that can be present almost anywhere on the planet. The study of trace elements in biotic matrices is a topic of great relevance for the implications that it can have on wildlife and human health. Penguins are very useful, since they live exclusively in the Southern Hemisphere and represent about 90% of the biomass of birds of the Southern Ocean. The levels of trace elements (dry weight) in different biotic matrices of penguins were reviewed here. Maps of trace element records in penguins were included. Data on exposure and effects of trace elements in penguins were collected from the literature. The most reported trace elements in penguins are aluminum, arsenic, cadmium, lead, mercury, copper, zinc, and manganese. Trace elements have been measured in 11 of the 18 species of penguins. The most studied biotic matrices are feathers and excreta. Most of the studies have been performed in Antarctica and subantarctic Islands. Little is known about the interaction among metals, which could provide better knowledge about certain mechanisms of detoxification in penguins. Future studies of trace elements in penguins must incorporate other metals such as vanadium, cobalt, nickel, and chromium. Data of metals in the species such as Eudyptes pachyrhynchus, Eudyptes moseleyi, Eudyptes sclateri, Eudyptes robustus, Eudyptes schlegeli, Spheniscus demersus, Spheniscus mendiculus, and Megadyptes antipodes are urged. It is important to correlate levels of metals in different biotic matrices with the effects on different species and in different geographic locations.

INAA Application for Trace Element Determination in Biological Reference Material

NASA Astrophysics Data System (ADS)

Atmodjo, D. P. D.; Kurniawati, S.; Lestiani, D. D.; Adventini, N.

2017-06-01

Trace element determination in biological samples is often used in the study of health and toxicology. Determination change to its essentiality and toxicity of trace element require an accurate determination method, which implies that a good Quality Control (QC) procedure should be performed. In this study, QC for trace element determination in biological samples was applied by analyzing the Standard Reference Material (SRM) Bovine muscle 8414 NIST using Instrumental Neutron Activation Analysis (INAA). Three selected trace element such as Fe, Zn, and Se were determined. Accuracy of the elements showed as %recovery and precision as %coefficient of variance (%CV). The result showed that %recovery of Fe, Zn, and Se were in the range between 99.4-107%, 92.7-103%, and 91.9-112%, respectively, whereas %CV were 2.92, 3.70, and 5.37%, respectively. These results showed that INAA method is precise and accurate for trace element determination in biological matrices.

Hippo pathway - brief overview of its relevance in cancer.

PubMed

Zygulska, A L; Krzemieniecki, K; Pierzchalski, P

2017-06-01

The Hippo pathway is the major regulator of organ growth and proliferation. Described initially in Drosophila, it is now recognized as one of the most conserved molecular pathways in all metazoan. Recent studies have revealed the Hippo signalling pathway might contribute to tumorigenesis and cancer development. The core components of the Hippo pathway include the mammalian sterile 20-like kinases (MSTs), large tumour suppressor kinases (LATSs), the adaptor proteins Salvador homologue 1 (SAV1, also called WW45) and Mps One Binder kinase activator proteins. The major target of the Hippo core kinases is the mammalian transcriptional activator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ). In cancer, the Hippo signalling is inactivated and YAP and TAZ are activated and free to translocate into the nucleus to promote cell proliferation. Nuclear YAP/TAZ activate or suppress transcription factors that regulate target genes involved in cell proliferation, tissue growth, control of organ size and shape or metastasis. The Hippo signalling pathway that controls the most important cellular processes like growth and division appears to be a very promising research subject in the field of cell biology and tissue engineering. It consists of elements that in the cell play the roles of tumour suppressors as well as oncogenes. This 'Janus like' - an opposite activity hidden within one and the same signalling pathway represents a significant obstacle for studying it. This property of the Hippo pathway is worth remembering, as it will appear several times during the discussion of its properties. Here, we will review certain data regarding biology of the Hippo signalling and its interplay with other prominent signalling pathways in the cell, its relevance in cancer development and therapies that might target elements of the Hippo pathway in most human cancers.

Computational exploration of cis-regulatory modules in rhythmic expression data using the "Exploration of Distinctive CREs and CRMs" (EDCC) and "CRM Network Generator" (CNG) programs.

PubMed

Bekiaris, Pavlos Stephanos; Tekath, Tobias; Staiger, Dorothee; Danisman, Selahattin

2018-01-01

Understanding the effect of cis-regulatory elements (CRE) and clusters of CREs, which are called cis-regulatory modules (CRM), in eukaryotic gene expression is a challenge of computational biology. We developed two programs that allow simple, fast and reliable analysis of candidate CREs and CRMs that may affect specific gene expression and that determine positional features between individual CREs within a CRM. The first program, "Exploration of Distinctive CREs and CRMs" (EDCC), correlates candidate CREs and CRMs with specific gene expression patterns. For pairs of CREs, EDCC also determines positional preferences of the single CREs in relation to each other and to the transcriptional start site. The second program, "CRM Network Generator" (CNG), prioritizes these positional preferences using a neural network and thus allows unbiased rating of the positional preferences that were determined by EDCC. We tested these programs with data from a microarray study of circadian gene expression in Arabidopsis thaliana. Analyzing more than 1.5 million pairwise CRE combinations, we found 22 candidate combinations, of which several contained known clock promoter elements together with elements that had not been identified as relevant to circadian gene expression before. CNG analysis further identified positional preferences of these CRE pairs, hinting at positional information that may be relevant for circadian gene expression. Future wet lab experiments will have to determine which of these combinations confer daytime specific circadian gene expression.

Computational exploration of cis-regulatory modules in rhythmic expression data using the “Exploration of Distinctive CREs and CRMs” (EDCC) and “CRM Network Generator” (CNG) programs

PubMed Central

Staiger, Dorothee

2018-01-01

Understanding the effect of cis-regulatory elements (CRE) and clusters of CREs, which are called cis-regulatory modules (CRM), in eukaryotic gene expression is a challenge of computational biology. We developed two programs that allow simple, fast and reliable analysis of candidate CREs and CRMs that may affect specific gene expression and that determine positional features between individual CREs within a CRM. The first program, “Exploration of Distinctive CREs and CRMs” (EDCC), correlates candidate CREs and CRMs with specific gene expression patterns. For pairs of CREs, EDCC also determines positional preferences of the single CREs in relation to each other and to the transcriptional start site. The second program, “CRM Network Generator” (CNG), prioritizes these positional preferences using a neural network and thus allows unbiased rating of the positional preferences that were determined by EDCC. We tested these programs with data from a microarray study of circadian gene expression in Arabidopsis thaliana. Analyzing more than 1.5 million pairwise CRE combinations, we found 22 candidate combinations, of which several contained known clock promoter elements together with elements that had not been identified as relevant to circadian gene expression before. CNG analysis further identified positional preferences of these CRE pairs, hinting at positional information that may be relevant for circadian gene expression. Future wet lab experiments will have to determine which of these combinations confer daytime specific circadian gene expression. PMID:29298348

Disorders of metal metabolism

PubMed Central

Ferreira, Carlos R.; Gahl, William A.

2017-01-01

Trace elements are chemical elements needed in minute amounts for normal physiology. Some of the physiologically relevant trace elements include iodine, copper, iron, manganese, zinc, selenium, cobalt and molybdenum. Of these, some are metals, and in particular, transition metals. The different electron shells of an atom carry different energy levels, with those closest to the nucleus being lowest in energy. The number of electrons in the outermost shell determines the reactivity of such an atom. The electron shells are divided in sub-shells, and in particular the third shell has s, p and d sub-shells. Transition metals are strictly defined as elements whose atom has an incomplete d sub-shell. This incomplete d sub-shell makes them prone to chemical reactions, particularly redox reactions. Transition metals of biologic importance include copper, iron, manganese, cobalt and molybdenum. Zinc is not a transition metal, since it has a complete d sub-shell. Selenium, on the other hand, is strictly speaking a nonmetal, although given its chemical properties between those of metals and nonmetals, it is sometimes considered a metalloid. In this review, we summarize the current knowledge on the inborn errors of metal and metalloid metabolism. PMID:29354481

Fractality à la carte: a general particle aggregation model.

PubMed

Nicolás-Carlock, J R; Carrillo-Estrada, J L; Dossetti, V

2016-01-19

In nature, fractal structures emerge in a wide variety of systems as a local optimization of entropic and energetic distributions. The fractality of these systems determines many of their physical, chemical and/or biological properties. Thus, to comprehend the mechanisms that originate and control the fractality is highly relevant in many areas of science and technology. In studying clusters grown by aggregation phenomena, simple models have contributed to unveil some of the basic elements that give origin to fractality, however, the specific contribution from each of these elements to fractality has remained hidden in the complex dynamics. Here, we propose a simple and versatile model of particle aggregation that is, on the one hand, able to reveal the specific entropic and energetic contributions to the clusters' fractality and morphology, and, on the other, capable to generate an ample assortment of rich natural-looking aggregates with any prescribed fractal dimension.

Optimizing Energy Transduction of Fluctuating Signals with Nanofluidic Diodes and Load Capacitors.

PubMed

Ramirez, Patricio; Cervera, Javier; Gomez, Vicente; Ali, Mubarak; Nasir, Saima; Ensinger, Wolfgang; Mafe, Salvador

2018-05-01

The design and experimental implementation of hybrid circuits is considered allowing charge transfer and energy conversion between nanofluidic diodes in aqueous ionic solutions and conventional electronic elements such as capacitors. The fundamental concepts involved are reviewed for the case of fluctuating zero-average external potentials acting on single pore and multipore membranes. This problem is relevant to electrochemical energy conversion and storage, the stimulus-response characteristics of nanosensors and actuators, and the estimation of the accumulative effects caused by external signals on biological ion channels. Half-wave and full-wave voltage doublers and quadruplers can scale up the transduction between ionic and electronic signals. The network designs discussed here should be useful to convert the weak signals characteristic of the micro and nanoscale into robust electronic responses by interconnecting iontronics and electronic elements. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phylogenetic shadowing of primate sequences to find functional regions of the human genome.

PubMed

Boffelli, Dario; McAuliffe, Jon; Ovcharenko, Dmitriy; Lewis, Keith D; Ovcharenko, Ivan; Pachter, Lior; Rubin, Edward M

2003-02-28

Nonhuman primates represent the most relevant model organisms to understand the biology of Homo sapiens. The recent divergence and associated overall sequence conservation between individual members of this taxon have nonetheless largely precluded the use of primates in comparative sequence studies. We used sequence comparisons of an extensive set of Old World and New World monkeys and hominoids to identify functional regions in the human genome. Analysis of these data enabled the discovery of primate-specific gene regulatory elements and the demarcation of the exons of multiple genes. Much of the information content of the comprehensive primate sequence comparisons could be captured with a small subset of phylogenetically close primates. These results demonstrate the utility of intraprimate sequence comparisons to discover common mammalian as well as primate-specific functional elements in the human genome, which are unattainable through the evaluation of more evolutionarily distant species.

Introduction to the application of QbD principles for the development of monoclonal antibodies.

PubMed

Finkler, Christof; Krummen, Lynne

2016-09-01

Quality by Design (QbD) is a global regulatory initiative with the goal of enhancing pharmaceutical development through the proactive design of pharmaceutical manufacturing process and controls to consistently deliver the intended performance of the product. The principles of pharmaceutical development relevant to QbD are described in the ICH guidance documents (ICHQ8-11). An integrated set of risk assessments and their related elements developed at Roche/Genentech were designed to provide an overview of product and process knowledge for the production of a recombinant monoclonal antibody. This chapter introduces a publication series on the application of Quality by Design for biopharmaceuticals, with a focus on the development of recombinant monoclonal antibodies. The development of and overview on the QbD concept applied by Roche and Genentech is described and essential QbD elements are presented. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Extended inheritance from an organizational point of view.

PubMed

Pontarotti, Gaëlle

2015-12-01

In this paper, I argue that the increasing data about non-genetic inheritance requires the construction of a new conceptual framework that should complement the inclusive approaches already discussed in the literature. More precisely, I hold that this framework should be epistemologically relevant for evolutionary biologists in capturing the limits of extended inheritance and in reassessing the boundaries of biological systems that transmit traits to their offspring. I outline the first elements of an organizational account of extended inheritance. In this account, the category of inherited factors is neither restricted to genes nor extended to stable resources related to trans-generational similarities. Instead, it includes persisting constitutive elements appearing as difference makers for heterogeneous organizational constraints, namely for heterogeneous constitutive parts whose specific role is to harness flows of matter and energy across generations of clearly delimited extended organized systems. This both inclusive and restrictive framework opens an additional way to apprehend how extended inheritance may affect evolutionary trajectories.

Piezoelectric sensors based on molecular imprinted polymers for detection of low molecular mass analytes.

PubMed

Uludağ, Yildiz; Piletsky, Sergey A; Turner, Anthony P F; Cooper, Matthew A

2007-11-01

Biomimetic recognition elements employed for the detection of analytes are commonly based on proteinaceous affibodies, immunoglobulins, single-chain and single-domain antibody fragments or aptamers. The alternative supra-molecular approach using a molecularly imprinted polymer now has proven utility in numerous applications ranging from liquid chromatography to bioassays. Despite inherent advantages compared with biochemical/biological recognition (which include robustness, storage endurance and lower costs) there are few contributions that describe quantitative analytical applications of molecularly imprinted polymers for relevant small molecular mass compounds in real-world samples. There is, however, significant literature describing the use of low-power, portable piezoelectric transducers to detect analytes in environmental monitoring and other application areas. Here we review the combination of molecularly imprinted polymers as recognition elements with piezoelectric biosensors for quantitative detection of small molecules. Analytes are classified by type and sample matrix presentation and various molecularly imprinted polymer synthetic fabrication strategies are also reviewed.

Why is migraine so common?

PubMed

Edmeads, J

1998-08-01

Migraine is clearly a very common biological disorder, but this knowledge has not been sufficient as yet to ensure completely effective treatment strategies. There appears to be discrepancy between what migraine patients desire as the outcome of consultations and what doctors think patients want. Patients seem, from Packard's selective study (11), to want explanation and reassurance before they get pain relief, whereas doctors view pain relief as the most important aim of management. It is possible that doctors still have underlying assumptions about psychological elements of migraine which color their perceptions of their patients. Communicating the relevance of scientific progress in migraine to neurologists and PCPs is an important challenge, as is calling attention to the patient's expectations from treatment. To be effective in improving education in this area, perhaps we should first ascertain the level of knowledge about the biology and treatment of headache among general neurologists.

Effective Educational Videos: Principles and Guidelines for Maximizing Student Learning from Video Content.

PubMed

Brame, Cynthia J

Educational videos have become an important part of higher education, providing an important content-delivery tool in many flipped, blended, and online classes. Effective use of video as an educational tool is enhanced when instructors consider three elements: how to manage cognitive load of the video; how to maximize student engagement with the video; and how to promote active learning from the video. This essay reviews literature relevant to each of these principles and suggests practical ways instructors can use these principles when using video as an educational tool. © 2016 C. J. Brame. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

New Elements To Consider When Modeling the Hazards Associated with Botulinum Neurotoxin in Food.

PubMed

Ihekwaba, Adaoha E C; Mura, Ivan; Malakar, Pradeep K; Walshaw, John; Peck, Michael W; Barker, G C

2016-01-15

Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the most potent biological substances known to mankind. BoNTs are the agents responsible for botulism, a rare condition affecting the neuromuscular junction and causing a spectrum of diseases ranging from mild cranial nerve palsies to acute respiratory failure and death. BoNTs are a potential biowarfare threat and a public health hazard, since outbreaks of foodborne botulism are caused by the ingestion of preformed BoNTs in food. Currently, mathematical models relating to the hazards associated with C. botulinum, which are largely empirical, make major contributions to botulinum risk assessment. Evaluated using statistical techniques, these models simulate the response of the bacterium to environmental conditions. Though empirical models have been successfully incorporated into risk assessments to support food safety decision making, this process includes significant uncertainties so that relevant decision making is frequently conservative and inflexible. Progression involves encoding into the models cellular processes at a molecular level, especially the details of the genetic and molecular machinery. This addition drives the connection between biological mechanisms and botulism risk assessment and hazard management strategies. This review brings together elements currently described in the literature that will be useful in building quantitative models of C. botulinum neurotoxin production. Subsequently, it outlines how the established form of modeling could be extended to include these new elements. Ultimately, this can offer further contributions to risk assessments to support food safety decision making. Copyright © 2015 Ihekwaba et al.

Analysis of diffusion in curved surfaces and its application to tubular membranes.

PubMed

Klaus, Colin James Stockdale; Raghunathan, Krishnan; DiBenedetto, Emmanuele; Kenworthy, Anne K

2016-12-01

Diffusion of particles in curved surfaces is inherently complex compared with diffusion in a flat membrane, owing to the nonplanarity of the surface. The consequence of such nonplanar geometry on diffusion is poorly understood but is highly relevant in the case of cell membranes, which often adopt complex geometries. To address this question, we developed a new finite element approach to model diffusion on curved membrane surfaces based on solutions to Fick's law of diffusion and used this to study the effects of geometry on the entry of surface-bound particles into tubules by diffusion. We show that variations in tubule radius and length can distinctly alter diffusion gradients in tubules over biologically relevant timescales. In addition, we show that tubular structures tend to retain concentration gradients for a longer time compared with a comparable flat surface. These findings indicate that sorting of particles along the surfaces of tubules can arise simply as a geometric consequence of the curvature without any specific contribution from the membrane environment. Our studies provide a framework for modeling diffusion in curved surfaces and suggest that biological regulation can emerge purely from membrane geometry. © 2016 Klaus, Raghunathan, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

TCGA Workflow: Analyze cancer genomics and epigenomics data using Bioconductor packages

PubMed Central

Bontempi, Gianluca; Ceccarelli, Michele; Noushmehr, Houtan

2016-01-01

Biotechnological advances in sequencing have led to an explosion of publicly available data via large international consortia such as The Cancer Genome Atlas (TCGA), The Encyclopedia of DNA Elements (ENCODE), and The NIH Roadmap Epigenomics Mapping Consortium (Roadmap). These projects have provided unprecedented opportunities to interrogate the epigenome of cultured cancer cell lines as well as normal and tumor tissues with high genomic resolution. The Bioconductor project offers more than 1,000 open-source software and statistical packages to analyze high-throughput genomic data. However, most packages are designed for specific data types (e.g. expression, epigenetics, genomics) and there is no one comprehensive tool that provides a complete integrative analysis of the resources and data provided by all three public projects. A need to create an integration of these different analyses was recently proposed. In this workflow, we provide a series of biologically focused integrative analyses of different molecular data. We describe how to download, process and prepare TCGA data and by harnessing several key Bioconductor packages, we describe how to extract biologically meaningful genomic and epigenomic data. Using Roadmap and ENCODE data, we provide a work plan to identify biologically relevant functional epigenomic elements associated with cancer. To illustrate our workflow, we analyzed two types of brain tumors: low-grade glioma (LGG) versus high-grade glioma (glioblastoma multiform or GBM). This workflow introduces the following Bioconductor packages: AnnotationHub, ChIPSeeker, ComplexHeatmap, pathview, ELMER, GAIA, MINET, RTCGAToolbox,  TCGAbiolinks. PMID:28232861

TCGA Workflow: Analyze cancer genomics and epigenomics data using Bioconductor packages.

PubMed

Silva, Tiago C; Colaprico, Antonio; Olsen, Catharina; D'Angelo, Fulvio; Bontempi, Gianluca; Ceccarelli, Michele; Noushmehr, Houtan

2016-01-01

Biotechnological advances in sequencing have led to an explosion of publicly available data via large international consortia such as The Cancer Genome Atlas (TCGA), The Encyclopedia of DNA Elements (ENCODE), and The NIH Roadmap Epigenomics Mapping Consortium (Roadmap). These projects have provided unprecedented opportunities to interrogate the epigenome of cultured cancer cell lines as well as normal and tumor tissues with high genomic resolution. The Bioconductor project offers more than 1,000 open-source software and statistical packages to analyze high-throughput genomic data. However, most packages are designed for specific data types (e.g. expression, epigenetics, genomics) and there is no one comprehensive tool that provides a complete integrative analysis of the resources and data provided by all three public projects. A need to create an integration of these different analyses was recently proposed. In this workflow, we provide a series of biologically focused integrative analyses of different molecular data. We describe how to download, process and prepare TCGA data and by harnessing several key Bioconductor packages, we describe how to extract biologically meaningful genomic and epigenomic data. Using Roadmap and ENCODE data, we provide a work plan to identify biologically relevant functional epigenomic elements associated with cancer. To illustrate our workflow, we analyzed two types of brain tumors: low-grade glioma (LGG) versus high-grade glioma (glioblastoma multiform or GBM). This workflow introduces the following Bioconductor packages: AnnotationHub, ChIPSeeker, ComplexHeatmap, pathview, ELMER, GAIA, MINET, RTCGAToolbox,  TCGAbiolinks.

Leadership and management influences the outcome of wildlife reintroduction programs: findings from the Sea Eagle Recovery Project.

PubMed

Sutton, Alexandra E

2015-01-01

Wildlife reintroductions and translocations are statistically unlikely to succeed. Nevertheless, they remain a critical part of conservation because they are the only way to actively restore a species into a habitat from which it has been extirpated. Past efforts to improve these practices have attributed the low success rate to failures in the biological knowledge (e.g., ignorance of social behavior, poor release site selection), or to the inherent challenges of reinstating a species into an area where threats have already driven it to local extinction. Such research presumes that the only way to improve reintroduction outcomes is through improved biological knowledge. This emphasis on biological solutions may have caused researchers to overlook the potential influence of other factors on reintroduction outcomes. I employed a grounded theory approach to study the leadership and management of a successful reintroduction program (the Sea Eagle Recovery Project in Scotland, UK) and identify four critical managerial elements that I theorize may have contributed to the successful outcome of this 50-year reintroduction. These elements are: 1. Leadership & Management: Small, dedicated team of accessible experts who provide strong political and scientific advocacy ("champions") for the project. 2. Hierarchy & Autonomy: Hierarchical management structure that nevertheless permits high individual autonomy. 3. Goals & Evaluation: Formalized goal-setting and regular, critical evaluation of the project's progress toward those goals. 4. Adaptive Public Relations: Adaptive outreach campaigns that are open, transparent, inclusive (esp. linguistically), and culturally relevant.

Automatic Screening for Perturbations in Boolean Networks.

PubMed

Schwab, Julian D; Kestler, Hans A

2018-01-01

A common approach to address biological questions in systems biology is to simulate regulatory mechanisms using dynamic models. Among others, Boolean networks can be used to model the dynamics of regulatory processes in biology. Boolean network models allow simulating the qualitative behavior of the modeled processes. A central objective in the simulation of Boolean networks is the computation of their long-term behavior-so-called attractors. These attractors are of special interest as they can often be linked to biologically relevant behaviors. Changing internal and external conditions can influence the long-term behavior of the Boolean network model. Perturbation of a Boolean network by stripping a component of the system or simulating a surplus of another element can lead to different attractors. Apparently, the number of possible perturbations and combinations of perturbations increases exponentially with the size of the network. Manually screening a set of possible components for combinations that have a desired effect on the long-term behavior can be very time consuming if not impossible. We developed a method to automatically screen for perturbations that lead to a user-specified change in the network's functioning. This method is implemented in the visual simulation framework ViSiBool utilizing satisfiability (SAT) solvers for fast exhaustive attractor search.

Lipidomics by ultrahigh performance liquid chromatography-high resolution mass spectrometry and its application to complex biological samples

PubMed Central

Triebl, Alexander; Trötzmüller, Martin; Hartler, Jürgen; Stojakovic, Tatjana; Köfeler, Harald C

2018-01-01

An improved approach for selective and sensitive identification and quantitation of lipid molecular species using reversed phase chromatography coupled to high resolution mass spectrometry was developed. The method is applicable to a wide variety of biological matrices using a simple liquid-liquid extraction procedure. Together, this approach combines three selectivity criteria: Reversed phase chromatography separates lipids according to their acyl chain length and degree of unsaturation and is capable of resolving positional isomers of lysophospholipids, as well as structural isomers of diacyl phospholipids and glycerolipids. Orbitrap mass spectrometry delivers the elemental composition of both positive and negative ions with high mass accuracy. Finally, automatically generated tandem mass spectra provide structural insight into numerous glycerolipids, phospholipids, and sphingolipids within a single run. Method validation resulted in a linearity range of more than four orders of magnitude, good values for accuracy and precision at biologically relevant concentration levels, and limits of quantitation of a few femtomoles on column. Hundreds of lipid molecular species were detected and quantified in three different biological matrices, which cover well the wide variety and complexity of various model organisms in lipidomic research. Together with a reliable software package, this method is a prime choice for global lipidomic analysis of even the most complex biological samples. PMID:28415015

Lipidomics by ultrahigh performance liquid chromatography-high resolution mass spectrometry and its application to complex biological samples.

PubMed

Triebl, Alexander; Trötzmüller, Martin; Hartler, Jürgen; Stojakovic, Tatjana; Köfeler, Harald C

2017-05-15

An improved approach for selective and sensitive identification and quantitation of lipid molecular species using reversed phase chromatography coupled to high resolution mass spectrometry was developed. The method is applicable to a wide variety of biological matrices using a simple liquid-liquid extraction procedure. Together, this approach combines multiple selectivity criteria: Reversed phase chromatography separates lipids according to their acyl chain length and degree of unsaturation and is capable of resolving positional isomers of lysophospholipids, as well as structural isomers of diacyl phospholipids and glycerolipids. Orbitrap mass spectrometry delivers the elemental composition of both positive and negative ions with high mass accuracy. Finally, automatically generated tandem mass spectra provide structural insight into numerous glycerolipids, phospholipids, and sphingolipids within a single run. Calibration showed linearity ranges of more than four orders of magnitude, good values for accuracy and precision at biologically relevant concentration levels, and limits of quantitation of a few femtomoles on column. Hundreds of lipid molecular species were detected and quantified in three different biological matrices, which cover well the wide variety and complexity of various model organisms in lipidomic research. Together with a software package, this method is a prime choice for global lipidomic analysis of even the most complex biological samples. Copyright © 2017 Elsevier B.V. All rights reserved.

BIOREL: the benchmark resource to estimate the relevance of the gene networks.

PubMed

Antonov, Alexey V; Mewes, Hans W

2006-02-06

The progress of high-throughput methodologies in functional genomics has lead to the development of statistical procedures to infer gene networks from various types of high-throughput data. However, due to the lack of common standards, the biological significance of the results of the different studies is hard to compare. To overcome this problem we propose a benchmark procedure and have developed a web resource (BIOREL), which is useful for estimating the biological relevance of any genetic network by integrating different sources of biological information. The associations of each gene from the network are classified as biologically relevant or not. The proportion of genes in the network classified as "relevant" is used as the overall network relevance score. Employing synthetic data we demonstrated that such a score ranks the networks fairly in respect to the relevance level. Using BIOREL as the benchmark resource we compared the quality of experimental and theoretically predicted protein interaction data.

A systematic approach to infer biological relevance and biases of gene network structures.

PubMed

Antonov, Alexey V; Tetko, Igor V; Mewes, Hans W

2006-01-10

The development of high-throughput technologies has generated the need for bioinformatics approaches to assess the biological relevance of gene networks. Although several tools have been proposed for analysing the enrichment of functional categories in a set of genes, none of them is suitable for evaluating the biological relevance of the gene network. We propose a procedure and develop a web-based resource (BIOREL) to estimate the functional bias (biological relevance) of any given genetic network by integrating different sources of biological information. The weights of the edges in the network may be either binary or continuous. These essential features make our web tool unique among many similar services. BIOREL provides standardized estimations of the network biases extracted from independent data. By the analyses of real data we demonstrate that the potential application of BIOREL ranges from various benchmarking purposes to systematic analysis of the network biology.

A versatile transfection assay system to evaluate the biological effects of diverse industrial chemicals.

PubMed

Koizumi, Shinji; Ohno, Shotaro; Otsuka, Fuminori

2012-01-01

Gene expression processes are now recognized as important targets of the toxic effects exerted by industrial chemicals. The transient transfection assay is a powerful tool to evaluate such effects. Thus, we developed a versatile assay system by constructing a basic reporter plasmid in which the regulatory DNA sequence to be studied can easily be substituted. To verify the performance of this system, reporter plasmids carrying any of the three distinct regulatory sequences, estrogen responsive element (ERE), glucocorticoid responsive element (GRE) and xenobiotic responsive element (XRE) were constructed. After transfection of human cells, these plasmids successfully expressed the relevant reporter genes in response to specific inducers, β-estradiol, dexamethasone and 3-methylcholanthrene, respectively. Several industrial chemicals were assayed using these reporter plasmids, and the ability of p-dimethylaminoazobenzene to elevate GRE- and XRE-mediated transcription was detected. α-Naphthylamine and o-tolidine were also observed to increase the XRE-mediated response. The transfection assay system established here will be useful to evaluate the effects of a wide variety of industrial chemicals.

New Developments in Hard X-ray Fluorescence Microscopy for In-situ Investigations of Trace Element Distributions in Aqueous Systems of Soil Colloids

NASA Astrophysics Data System (ADS)

Gleber, Sophie-Charlotte; Weinhausen, Britta; Köster, Sarah; Ward, Jesse; Vine, David; Finney, Lydia; Vogt, Stefan

2013-10-01

The distribution, binding and release of trace elements on soil colloids determine matter transport through the soil matrix, and necessitates an aqueous environment and short length and time scales for their study. However, not many microscopy techniques allow for that. We previously showed hard x-ray fluorescence microscopy capabilities to image aqueous colloidal soil samples [1]. As this technique provides attogram sensitivity for transition elements like Cu, Zn, and other geochemically relevant trace elements at sub micrometer spatial resolution (currently down to 150 nm at 2-ID-E [2]; below 50nm at Bionanoprobe, cf. G.Woloschak et al, this volume) combined with the capability to penetrate tens of micrometer of water, it is ideally suited for imaging the elemental content of soil colloids. To address the question of binding and release processes of trace elements on the surface of soil colloids, we developed a microfluidics based XRF flow cytometer, and expanded the applied methods of hard x-ray fluorescence microscopy towards three dimensional imaging. Here, we show (a) the 2-D imaged distributions of Si, K and Fe on soil colloids of Pseudogley samples; (b) how the trace element distribution is a dynamic, pH-dependent process; and (c) x-ray tomographic applications to render the trace elemental distributions in 3-D. We conclude that the approach presented here shows the remarkable potential to image and quantitate elemental distributions from samles within their natural aqueous microenvironment, particularly important in the environmental, medical, and biological sciences.

A framework for characterizing drug information sources.

PubMed

Sharp, Mark; Bodenreider, Olivier; Wacholder, Nina

2008-11-06

Drug information is complex, voluminous, heterogeneous, and dynamic. Multiple sources are available, each providing some elements of information about drugs (usually for a given purpose), but there exists no integrated view or directory that could be used to locate sources appropriate to a given purpose. We examined 23 sources that provide drug information in the pharmacy, chemistry, biology, and clinical medicine domains. Their drug information content could be categorized with 39 dimensions. We propose this list of dimensions as a framework for characterizing drug information sources. As an evaluation, we show that this framework is useful for comparing drug information sources and selecting sources most relevant to a given use case.

Ash aggregation enhanced by deposition and redistribution of salt on the surface of volcanic ash in eruption plumes.

PubMed

Mueller, Sebastian B; Ayris, Paul M; Wadsworth, Fabian B; Kueppers, Ulrich; Casas, Ana S; Delmelle, Pierre; Taddeucci, Jacopo; Jacob, Michael; Dingwell, Donald B

2017-03-31

Interactions with volcanic gases in eruption plumes produce soluble salt deposits on the surface of volcanic ash. While it has been postulated that saturation-driven precipitation of salts following the dissolution of ash surfaces by condensed acidic liquids is a primary mechanism of salt formation during an eruption, it is only recently that this mechanism has been subjected to detailed study. Here we spray water and HCl droplets into a suspension of salt-doped synthetic glass or volcanic ash particles, and produce aggregates. Deposition of acidic liquid droplets on ash particles promotes dissolution of existing salts and leaches cations from the underlying material surface. The flow of liquid, due to capillary forces, will be directed to particle-particle contact points where subsequent precipitation of salts will cement the aggregate. Our data suggest that volcanically-relevant loads of surface salts can be produced by acid condensation in eruptive settings. Several minor and trace elements mobilised by surface dissolution are biologically relevant; geographic areas with aggregation-mediated ash fallout could be "hotspots" for the post-deposition release of these elements. The role of liquids in re-distributing surface salts and cementing ash aggregates also offers further insight into the mechanisms which preserve well-structured aggregates in some ash deposits.

Ash aggregation enhanced by deposition and redistribution of salt on the surface of volcanic ash in eruption plumes

PubMed Central

Mueller, Sebastian B.; Ayris, Paul M.; Wadsworth, Fabian B.; Kueppers, Ulrich; Casas, Ana S.; Delmelle, Pierre; Taddeucci, Jacopo; Jacob, Michael; Dingwell, Donald B.

2017-01-01

Interactions with volcanic gases in eruption plumes produce soluble salt deposits on the surface of volcanic ash. While it has been postulated that saturation-driven precipitation of salts following the dissolution of ash surfaces by condensed acidic liquids is a primary mechanism of salt formation during an eruption, it is only recently that this mechanism has been subjected to detailed study. Here we spray water and HCl droplets into a suspension of salt-doped synthetic glass or volcanic ash particles, and produce aggregates. Deposition of acidic liquid droplets on ash particles promotes dissolution of existing salts and leaches cations from the underlying material surface. The flow of liquid, due to capillary forces, will be directed to particle-particle contact points where subsequent precipitation of salts will cement the aggregate. Our data suggest that volcanically-relevant loads of surface salts can be produced by acid condensation in eruptive settings. Several minor and trace elements mobilised by surface dissolution are biologically relevant; geographic areas with aggregation-mediated ash fallout could be “hotspots” for the post-deposition release of these elements. The role of liquids in re-distributing surface salts and cementing ash aggregates also offers further insight into the mechanisms which preserve well-structured aggregates in some ash deposits. PMID:28361966

Statistically Validated Networks in Bipartite Complex Systems

PubMed Central

Tumminello, Michele; Miccichè, Salvatore; Lillo, Fabrizio; Piilo, Jyrki; Mantegna, Rosario N.

2011-01-01

Many complex systems present an intrinsic bipartite structure where elements of one set link to elements of the second set. In these complex systems, such as the system of actors and movies, elements of one set are qualitatively different than elements of the other set. The properties of these complex systems are typically investigated by constructing and analyzing a projected network on one of the two sets (for example the actor network or the movie network). Complex systems are often very heterogeneous in the number of relationships that the elements of one set establish with the elements of the other set, and this heterogeneity makes it very difficult to discriminate links of the projected network that are just reflecting system's heterogeneity from links relevant to unveil the properties of the system. Here we introduce an unsupervised method to statistically validate each link of a projected network against a null hypothesis that takes into account system heterogeneity. We apply the method to a biological, an economic and a social complex system. The method we propose is able to detect network structures which are very informative about the organization and specialization of the investigated systems, and identifies those relationships between elements of the projected network that cannot be explained simply by system heterogeneity. We also show that our method applies to bipartite systems in which different relationships might have different qualitative nature, generating statistically validated networks in which such difference is preserved. PMID:21483858

The Elemental Analysis of Biological and Environmental Materials Using a 2MEV Proton Beam

NASA Astrophysics Data System (ADS)

Arshed, Waheed

Available from UMI in association with The British Library. A programme has been developed to simulate the proton induced x-ray emission (PIXE) spectra and its uses have been described. The PIXE technique has been applied to the analysis of new biological reference materials which consist of IAEA human diet samples and NIST leaf samples. Homogeneity of these and two existing reference materials, IAEA soil -7 and Bowen's kale, has also been determined at the mug scale. A subsample representative of a material is ascertained by determination of sampling factors for the elements detected in the material. Proton induced gamma-ray emission (PIGE) analysis in conjunction with PIXE has been employed to investigate F and other elemental concentrations found in human teeth samples. The mean F concentration in enamel and dentine parts of teeth followed an age dependent model. Concentrations of Ca and P were found to be higher in the enamel than in the dentine. Analysis of blood and its components in the study of elemental models in sickle cell disease in Nigerians has been carried out. Comparisons revealed that Cl, Ca and Cu were at higher levels whereas K, Fe, Zn and Rb were at lower levels in the whole blood of the sicklers compared to controls. Similar results were obtained for the erythrocytes except that Br was found at higher concentration in erythrocytes of the sicklers. Higher concentrations of Cl, K, Fe and Cu were also observed in plasma of the sicklers compared to controls. PIXE and scanning electron microscopy (SEM) were used in the characterization of the Harmattan dust particulates collected at Kano and Ife. Most of the elements were found to be at higher concentrations as compared to those found in Recife (Brazil) and Toronto (Canada). The value of total suspended particulate was above the relevant national air quality standards. PIXE in conjunction with Rutherford backscattering spectrometry and instrumental neutron activation analysis was employed in the analysis of soil samples detecting 31 elements. The results have been discussed with reference to elemental concentrations and Ca/Si ratio. The latter was a valid indicator of soil pollution by the cement dust. (Abstract shortened by UMI.).

Alternative splicing of anciently exonized 5S rRNA regulates plant transcription factor TFIIIA

PubMed Central

Fu, Yan; Bannach, Oliver; Chen, Hao; Teune, Jan-Hendrik; Schmitz, Axel; Steger, Gerhard; Xiong, Liming; Barbazuk, W. Brad

2009-01-01

Identifying conserved alternative splicing (AS) events among evolutionarily distant species can prioritize AS events for functional characterization and help uncover relevant cis- and trans-regulatory factors. A genome-wide search for conserved cassette exon AS events in higher plants revealed the exonization of 5S ribosomal RNA (5S rRNA) within the gene of its own transcription regulator, TFIIIA (transcription factor for polymerase III A). The 5S rRNA-derived exon in TFIIIA gene exists in all representative land plant species but not in green algae and nonplant species, suggesting it is specific to land plants. TFIIIA is essential for RNA polymerase III-based transcription of 5S rRNA in eukaryotes. Integrating comparative genomics and molecular biology revealed that the conserved cassette exon derived from 5S rRNA is coupled with nonsense-mediated mRNA decay. Utilizing multiple independent Arabidopsis overexpressing TFIIIA transgenic lines under osmotic and salt stress, strong accordance between phenotypic and molecular evidence reveals the biological relevance of AS of the exonized 5S rRNA in quantitative autoregulation of TFIIIA homeostasis. Most significantly, this study provides the first evidence of ancient exaptation of 5S rRNA in plants, suggesting a novel gene regulation model mediated by the AS of an anciently exonized noncoding element. PMID:19211543

An Integrated XRF/XRD Instrument for Mars Exobiology and Geology Experiments

NASA Technical Reports Server (NTRS)

Koppel, L. N.; Franco, E. D.; Kerner, J. A.; Fonda, M. L.; Schwartz, D. E.; Marshall, J. R.

1993-01-01

By employing an integrated x-ray instrument on a future Mars mission, data obtained will greatly augment those returned by Viking; details characterizing the past and present environment on Mars and those relevant to the possibility of the origin and evolution of life will be acquired. A combined x-ray fluorescence/x-ray diffraction (XRF/XRD) instrument was breadboarded and demonstrated to accommodate important exobiology and geology experiment objectives outlined for MESUR and future Mars missions. Among others, primary objectives for the exploration of Mars include the intense study of local areas on Mars to establish the chemical, mineralogical, and petrological character of different components of the surface material; to determine the distribution, abundance, and sources and sinks of volatile materials, including an assessment of the biologic potential, now and during past epoches; and to establish the global chemical and physical characteristics of the Martian surface. The XRF/XRD breadboard instrument identifies and quantifies soil surface elemental, mineralogical, and petrological characteristics and acquires data necessary to address questions on volatile abundance and distribution. Additionally, the breadboard is able to characterize the biogenic element constituents of soil samples providing information on the biologic potential of the Mars environment. Preliminary breadboard experiments confirmed the fundamental instrument design approach and measurement performance.

Investigation of production method, geographical origin and species authentication in commercially relevant shrimps using stable isotope ratio and/or multi-element analyses combined with chemometrics: an exploratory analysis.

PubMed

Ortea, Ignacio; Gallardo, José M

2015-03-01

Three factors defining the traceability of a food product are production method (wild or farmed), geographical origin and biological species, which have to be checked and guaranteed, not only in order to avoid mislabelling and commercial fraud, but also to address food safety issues and to comply with legal regulations. The aim of this study was to determine whether these three factors could be differentiated in shrimps using stable isotope ratio analysis of carbon and nitrogen and/or multi-element composition. Different multivariate statistics methods were applied to different data subsets in order to evaluate their performance in terms of classification or predictive ability. Although the success rates varied depending on the dataset used, the combination of both techniques allowed the correct classification of 100% of the samples according to their actual origin and method of production, and 93.5% according to biological species. Even though further studies including a larger number of samples in each group are needed in order to validate these findings, we can conclude that these methodologies should be considered for studies regarding seafood product authenticity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Boron uptake, localization, and speciation in marine brown algae.

PubMed

Miller, Eric P; Wu, Youxian; Carrano, Carl J

2016-02-01

In contrast to the generally boron-poor terrestrial environment, the concentration of boron in the marine environment is relatively high (0.4 mM) and while there has been extensive interest in its use as a surrogate of pH in paleoclimate studies in the context of climate change-related questions, the relatively depth independent, and the generally non-nutrient-like concentration profile of this element have led to boron being neglected as a potentially biologically relevant element in the ocean. Among the marine plant-like organisms the brown algae (Phaeophyta) are one of only five lineages of photosynthetic eukaryotes to have evolved complex multicellularity. Many of unusual and often unique features of brown algae are attributable to this singular evolutionary history. These adaptations are a reflection of the marine coastal environment which brown algae dominate in terms of biomass. Consequently, brown algae are of fundamental importance to oceanic ecology, geochemistry, and coastal industry. Our results indicate that boron is taken up by a facilitated diffusion mechanism against a considerable concentration gradient. Furthermore, in both Ectocarpus and Macrocystis some boron is most likely bound to cell wall constituent alginate and the photoassimilate mannitol located in sieve cells. Herein, we describe boron uptake, speciation, localization and possible biological function in two species of brown algae, Macrocystis pyrifera and Ectocarpus siliculosus.

Students' reasoning about "high-energy bonds" and ATP: A vision of interdisciplinary education

NASA Astrophysics Data System (ADS)

Dreyfus, Benjamin W.; Sawtelle, Vashti; Turpen, Chandra; Gouvea, Julia; Redish, Edward F.

2014-06-01

As interdisciplinary courses are developed, instructors and researchers have to grapple with questions of how students should make connections across disciplines. We explore the issue of interdisciplinary reconciliation (IDR): how students reconcile seemingly contradictory ideas from different disciplines. While IDR has elements in common with other frameworks for the reconciliation of ideas across contexts, it differs in that each disciplinary idea is considered canonically correct within its own discipline. The setting for the research is an introductory physics course for biology majors that seeks to build greater interdisciplinary coherence and therefore includes biologically relevant topics such as adenosine triphosphate (ATP) and chemical bond energy. In our case-study data, students grapple with the apparent contradiction between the energy released when the phosphate bond in ATP is broken and the idea that an energy input is required to break a bond. We see students justifying context-dependent modeling choices, showing nuance in articulating how system choices may be related to disciplinary problems of interest. This represents a desired end point of IDR, in which students can build coherent connections between concepts from different disciplines while understanding each concept in its own disciplinary context. Our case study also illustrates elements of the instructional environment that play roles in the process of IDR.

Imaging mass spectrometer with mass tags

DOEpatents

Felton, James S.; Wu, Kuang Jen; Knize, Mark G.; Kulp, Kristen S.; Gray, Joe W.

2010-06-01

A method of analyzing biological material by exposing the biological material to a recognition element, that is coupled to a mass tag element, directing an ion beam of a mass spectrometer to the biological material, interrogating at least one region of interest area from the biological material and producing data, and distributing the data in plots.

NASA Strategy to Safely Live and Work in the Space Radiation Environment

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Wu, Honglu; Corbin, Barbara J.; Sulzman, Frank M.; Krenek, Sam

2007-01-01

In space, astronauts are constantly bombarded with energetic particles. The goal of the National Aeronautics and Space Agency and the NASA Space Radiation Project is to ensure that astronauts can safely live and work in the space radiation environment. The space radiation environment poses both acute and chronic risks to crew health and safety, but unlike some other aspects of space travel, space radiation exposure has clinically relevant implications for the lifetime of the crew. Among the identified radiation risks are cancer, acute and late CNS damage, chronic and degenerative tissue decease, and acute radiation syndrome. The term "safely" means that risks are sufficiently understood such that acceptable limits on mission, post-mission and multi-mission consequences can be defined. The NASA Space Radiation Project strategy has several elements. The first element is to use a peer-reviewed research program to increase our mechanistic knowledge and genetic capabilities to develop tools for individual risk projection, thereby reducing our dependency on epidemiological data and population-based risk assessment. The second element is to use the NASA Space Radiation Laboratory to provide a ground-based facility to study the health effects/mechanisms of damage from space radiation exposure and the development and validation of biological models of risk, as well as methods for extrapolation to human risk. The third element is a risk modeling effort that integrates the results from research efforts into models of human risk to reduce uncertainties in predicting the identified radiation risks. To understand the biological basis for risk, we must also understand the physical aspects of the crew environment. Thus, the fourth element develops computer algorithms to predict radiation transport properties, evaluate integrated shielding technologies and provide design optimization recommendations for the design of human space systems. Understanding the risks and determining methods to mitigate the risks are keys to a successful radiation protection strategy.

Trace Element Analysis of Biological Samples.

ERIC Educational Resources Information Center

Veillon, Claude

1986-01-01

Reviews background of atomic absorption spectrometry techniques. Discusses problems encountered and precautions to be taken in determining trace elements in the parts-per-billion concentration range and below. Concentrates on determining chromium in biological samples by graphite furnace atomic absorption. Considers other elements, matrices, and…

Functional networks inference from rule-based machine learning models.

PubMed

Lazzarini, Nicola; Widera, Paweł; Williamson, Stuart; Heer, Rakesh; Krasnogor, Natalio; Bacardit, Jaume

2016-01-01

Functional networks play an important role in the analysis of biological processes and systems. The inference of these networks from high-throughput (-omics) data is an area of intense research. So far, the similarity-based inference paradigm (e.g. gene co-expression) has been the most popular approach. It assumes a functional relationship between genes which are expressed at similar levels across different samples. An alternative to this paradigm is the inference of relationships from the structure of machine learning models. These models are able to capture complex relationships between variables, that often are different/complementary to the similarity-based methods. We propose a protocol to infer functional networks from machine learning models, called FuNeL. It assumes, that genes used together within a rule-based machine learning model to classify the samples, might also be functionally related at a biological level. The protocol is first tested on synthetic datasets and then evaluated on a test suite of 8 real-world datasets related to human cancer. The networks inferred from the real-world data are compared against gene co-expression networks of equal size, generated with 3 different methods. The comparison is performed from two different points of view. We analyse the enriched biological terms in the set of network nodes and the relationships between known disease-associated genes in a context of the network topology. The comparison confirms both the biological relevance and the complementary character of the knowledge captured by the FuNeL networks in relation to similarity-based methods and demonstrates its potential to identify known disease associations as core elements of the network. Finally, using a prostate cancer dataset as a case study, we confirm that the biological knowledge captured by our method is relevant to the disease and consistent with the specialised literature and with an independent dataset not used in the inference process. The implementation of our network inference protocol is available at: http://ico2s.org/software/funel.html.

Genotoxicity testing on the international space station: Preparatory work on the SOS-LUX test as part of the space experiment TRIPLE-LUX

NASA Astrophysics Data System (ADS)

Stojicic, Nevena; Walrafen, David; Baumstark-Khan, Christa; Rabbow, Elke; Rettberg, Petra; Weisshaar, Maria-Paz; Horneck, Gerda

Harmful environmental factors - namely ionizing radiation - will continue to influence future manned space missions. The Radiation Biology Unit at the German Aerospace Center (DLR) develops cellular monitoring systems, which include bacterial and mammalian cell systems capable of recognizing DNA damage as a consequence of the presence of genotoxic conditions. Such a bioassay is the SOS-LUX test, which represents the radiobiological part of the German space experiment "Gene, immune and cellular responses to single and combined space flight conditions (TRIPLE-LUX)" which has been selected by the IDI/USRA Peer Review Panel for NASA/ESA to be performed on the International Space Station (ISS). It will supply basic information on the genotoxic response to radiation applied in microgravity. The biological end-point under investigation will depend on the bacterial SOS response brought about by genetically modified bacteria that are transformed with the pSWITCH plasmid (constructed from the plasmids pPLS-1 and pGFPuv). The luminescent/fluorescent bioassay SWITCH (SWITCH: Salmonella Weighting of Induced Toxicity Cyto/GenoTox for Human Health) as successor of the SOS-LUX test for rapid toxicity (genotoxicity and cytotoxicity) testing, makes use of two sensing and reporting systems for the two biological endpoints under investigation: the SOS-LUX test and the LAC- Fluoro test. The SWITCH plasmid carries the promoterless lux operon of Photobacterium leiognathi as reporter element under the control of the DNA-damage-dependent SOS promoter of ColD as sensor element (for genotoxicity testing) and the sequences for a hybrid protein consisting of β-galactosidase and GFPuv of Aequorea victoria as reporter element under the control of the (in Salmonella constitutively active) LAC promoter of Escherichia coli as sensor element (for cytotoxicity testing). The system has worked properly for terrestrial applications during the first experiments. Experiments using X-rays and UV radiation of various qualities (from UVC to UVA) have given insights into cellular mechanisms relevant for estimation of health risks, resulting from exposure of astronauts to the extraordinary radiation environment of space.

The nature of placebo response in clinical studies of major depressive disorder.

PubMed

Papakostas, George I; Østergaard, Søren D; Iovieno, Nadia

2015-04-01

To review factors influencing placebo response and clinical trial outcome in depression, and suggest ways to optimize trial success in mood disorders. PubMed searches were conducted by cross-referencing the terms depression, depressive with placebo, clinical trial, and clinical trials for studies published in English between 1970 and September 2013. Relevant abstracts were identified in PubMed, including clinical trials, quantitative studies, and qualitative research. We obtained and reviewed relevant articles and utilized their information to synthesize the present review. Included articles were grouped in the following areas of relevance: (1) biological validity of illness, (2) baseline severity of illness, (3) chronicity of the index episode of depression, (4) age of participants, (5) medical and psychiatric comorbidity, (6) probability of receiving placebo, (7) use of prospective treatment phases (lead-in) (8) dosing schedule, (9) trial duration, (10) frequency of follow-up assessments, and (11) study outcome measure. Several key elements emerge as critical to the ultimate success of a clinical trial, including the probability of receiving placebo, study duration, dosing schedule, visit frequency, the use of blinded lead-in phases, the use of centralized raters, illness severity and duration, and comorbid anxiety. Our increasing understanding of the placebo response in clinical trials of major depressive disorder lends to a, gradually, more predictable phenomenon and, hopefully, to one that becomes lesser in magnitude and variability. Several elements have emerged that seem to play a critical role in trial success, gradually reshaping the design of clinical, translational, as well as mechanistic studies in depression. © Copyright 2015 Physicians Postgraduate Press, Inc.

Mutational studies reveal a complex set of positive and negative control elements within the chicken vitellogenin II promoter.

PubMed

Seal, S N; Davis, D L; Burch, J B

1991-05-01

The endogenous chicken vitellogenin II (VTGII) gene is transcribed exclusively in hepatocytes in response to estrogen. We previously identified two estrogen response elements (EREs) upstream of this gene. We now present an analysis of the VTGII promoter activated by these EREs in response to estrogen. Chimeric VTGII-CAT genes were cotransfected into LMH chicken hepatoma cells along with an estrogen receptor expression vector, and transient CAT expression was assayed after culturing the cells in the absence or presence of estrogen. An analysis of constructs bearing deletions downstream of the more proximal ERE indicated that promoter elements relevant to transcription in LMH cells extend to between -113 and -96. The relative importance of sequences within the VTGII promoter was examined by using 10 contiguous linker scanner mutations spanning the region from -117 to -24. Although most of these mutations compromised VTGII promoter function, one dramatically increased expression in LMH cells and also rendered the VTGII promoter capable of being activated by cis-linked EREs in fibroblasts cotransfected with an estrogen receptor expression vector. Gel retardation and DNase I footprinting assays revealed four factor-binding sites within this promoter. We demonstrate that three of these sites bind C/EBP, SP1, and USF (or related factors), respectively; the fourth site binds a factor that we denote TF-V beta. The biological relevance of these findings is suggested by the fact that three of these binding sites map to sites previously shown to be occupied in vivo in response to estrogen.

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,…

Subset selective search on the basis of color and preview.

PubMed

Donk, Mieke

2017-01-01

In the preview paradigm observers are presented with one set of elements (the irrelevant set) followed by the addition of a second set among which the target is presented (the relevant set). Search efficiency in such a preview condition has been demonstrated to be higher than that in a full-baseline condition in which both sets are simultaneously presented, suggesting that a preview of the irrelevant set reduces its influence on the search process. However, numbers of irrelevant and relevant elements are typically not independently manipulated. Moreover, subset selective search also occurs when both sets are presented simultaneously but differ in color. The aim of the present study was to investigate how numbers of irrelevant and relevant elements contribute to preview search in the absence and presence of a color difference between subsets. In two experiments it was demonstrated that a preview reduced the influence of the number of irrelevant elements in the absence but not in the presence of a color difference between subsets. In the presence of a color difference, a preview lowered the effect of the number of relevant elements but only when the target was defined by a unique feature within the relevant set (Experiment 1); when the target was defined by a conjunction of features (Experiment 2), search efficiency as a function of the number of relevant elements was not modulated by a preview. Together the results are in line with the idea that subset selective search is based on different simultaneously operating mechanisms.

Auditory-visual object recognition time suggests specific processing for animal sounds.

PubMed

Suied, Clara; Viaud-Delmon, Isabelle

2009-01-01

Recognizing an object requires binding together several cues, which may be distributed across different sensory modalities, and ignoring competing information originating from other objects. In addition, knowledge of the semantic category of an object is fundamental to determine how we should react to it. Here we investigate the role of semantic categories in the processing of auditory-visual objects. We used an auditory-visual object-recognition task (go/no-go paradigm). We compared recognition times for two categories: a biologically relevant one (animals) and a non-biologically relevant one (means of transport). Participants were asked to react as fast as possible to target objects, presented in the visual and/or the auditory modality, and to withhold their response for distractor objects. A first main finding was that, when participants were presented with unimodal or bimodal congruent stimuli (an image and a sound from the same object), similar reaction times were observed for all object categories. Thus, there was no advantage in the speed of recognition for biologically relevant compared to non-biologically relevant objects. A second finding was that, in the presence of a biologically relevant auditory distractor, the processing of a target object was slowed down, whether or not it was itself biologically relevant. It seems impossible to effectively ignore an animal sound, even when it is irrelevant to the task. These results suggest a specific and mandatory processing of animal sounds, possibly due to phylogenetic memory and consistent with the idea that hearing is particularly efficient as an alerting sense. They also highlight the importance of taking into account the auditory modality when investigating the way object concepts of biologically relevant categories are stored and retrieved.

Repeatability and reproducibility of intracellular molar concentration assessed by synchrotron-based x-ray fluorescence microscopy

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

Merolle, L., E-mail: lucia.merolle@elettra.eu; Gianoncelli, A.; Malucelli, E., E-mail: emil.malucelli@unibo.it

2016-01-28

Elemental analysis of biological sample can give information about content and distribution of elements essential for human life or trace elements whose absence is the cause of abnormal biological function or development. However, biological systems contain an ensemble of cells with heterogeneous chemistry and elemental content; therefore, accurate characterization of samples with high cellular heterogeneity may only be achieved by analyzing single cells. Powerful methods in molecular biology are abundant, among them X-Ray microscopy based on synchrotron light source has gaining increasing attention thanks to its extremely sensitivity. However, reproducibility and repeatability of these measurements is one of the majormore » obstacles in achieving a statistical significance in single cells population analysis. In this study, we compared the elemental content of human colon adenocarcinoma cells obtained by three distinct accesses to synchrotron radiation light.« less

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

PubMed

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

2017-07-01

Genome-wide association study (GWAS)-identified variants are enriched for functional elements. However, we have limited knowledge of how functional enrichment may differ by disease/trait and tissue type. We tested a broad set of eight functional elements for enrichment among GWAS-identified SNPs (p < 5×10 -8 ) from the NHGRI-EBI Catalog across seven disease/trait categories: cancer, cardiovascular disease, diabetes, autoimmune disease, psychiatric disease, neurological disease, and anthropometric traits. SNPs were annotated using HaploReg for the eight functional elements across any tissue: DNase sites, expression quantitative trait loci (eQTL), sequence conservation, enhancers, promoters, missense variants, sequence motifs, and protein binding sites. In addition, tissue-specific annotations were considered for brain vs. blood. Disease/trait SNPs were compared to a control set of 4809 SNPs matched to the GWAS SNPs (N = 1639) on allele frequency, gene density, distance to nearest gene, and linkage disequilibrium at ~3:1 ratio. Enrichment analyses were conducted using logistic regression, with Bonferroni correction. Overall, a significant enrichment was observed for all functional elements, except sequence motifs. Missense SNPs showed the strongest magnitude of enrichment. eQTLs were the only functional element significantly enriched across all diseases/traits. Magnitudes of enrichment were generally similar across diseases/traits, where enrichment was statistically significant. Blood vs. brain tissue effects on enrichment were dependent on disease/trait and functional element (e.g., cardiovascular disease: eQTLs P TissueDifference  = 1.28 × 10 -6 vs. enhancers P TissueDifference  = 0.94). Identifying disease/trait-relevant functional elements and tissue types could provide new insight into the underlying biology, by guiding a priori GWAS analyses (e.g., brain enhancer elements for psychiatric disease) or facilitating post hoc interpretation.

Emergy Evaluations of the Global Biogeochemical Cycles of Six Biologically Active Elements and Two Compounds

EPA Science Inventory

Estimates of the emergy carried by the flows of biologically active elements (BAE) and compounds are needed to accurately evaluate the near and far field effects of anthropogenic wastes. The transformities and specific emergies of these elements and of their different chemical sp...

A review of chromatographic methods for the determination of water- and fat-soluble vitamins in biological fluids.

PubMed

Karaźniewicz-Łada, Marta; Główka, Anna

2016-01-01

Vitamins are an essential element of nutrition and thus contribute to human health. Vitamins catalyze many biochemical reactions and their lack or excess can cause health problems. Therefore, monitoring vitamin concentrations in plasma or other biological fluids may be useful in the diagnosis of various disorders as well as in the treatment process. Several chromatographic methods have been developed for the determination of these compounds in biological samples, including high-performance liquid chromatography with UV and fluorescence detection. Recently, high-performance liquid chromatography with tandem mass spectrometry methods have been widely used for the determination of vitamins in complex matrices because of their high sensitivity and selectivity. This method requires preconditioning of samples for analysis, including protein precipitation and/or various extraction techniques. The choice of method may depend on the desired cost, convenience, turnaround time, specificity, and accuracy of the information to be obtained. This article reviews the recently reported chromatographic methods used for determination of vitamins in biological fluids. Relevant papers published mostly during the last 5 years were identified by an extensive PubMed search using appropriate keywords. Particular attention was given to the preparation steps and extraction techniques. This report may be helpful in the selection of procedures that are appropriate for certain types of biological materials and analytes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modularization of genetic elements promotes synthetic metabolic engineering.

PubMed

Qi, Hao; Li, Bing-Zhi; Zhang, Wen-Qian; Liu, Duo; Yuan, Ying-Jin

2015-11-15

In the context of emerging synthetic biology, metabolic engineering is moving to the next stage powered by new technologies. Systematical modularization of genetic elements makes it more convenient to engineer biological systems for chemical production or other desired purposes. In the past few years, progresses were made in engineering metabolic pathway using synthetic biology tools. Here, we spotlighted the topic of implementation of modularized genetic elements in metabolic engineering. First, we overviewed the principle developed for modularizing genetic elements and then discussed how the genetic modules advanced metabolic engineering studies. Next, we picked up some milestones of engineered metabolic pathway achieved in the past few years. Last, we discussed the rapid raised synthetic biology field of "building a genome" and the potential in metabolic engineering. Copyright © 2015 Elsevier Inc. All rights reserved.

Submicron scale tissue multifractal anisotropy in polarized laser light scattering

NASA Astrophysics Data System (ADS)

Das, Nandan Kumar; Dey, Rajib; Chakraborty, Semanti; Panigrahi, Prasanta K.; Meglinski, Igor; Ghosh, Nirmalya

2018-03-01

The spatial fluctuations of the refractive index within biological tissues exhibit multifractal anisotropy, leaving its signature as a spectral linear diattenuation of scattered polarized light. The multifractal anisotropy has been quantitatively assessed by the processing of relevant Mueller matrix elements in the Fourier domain, utilizing the Born approximation and subsequent multifractal analysis. The differential scaling exponent and width of the singularity spectrum appear to be highly sensitive to the structural multifractal anisotropy at the micron/sub-micron length scales. An immediate practical use of these multifractal anisotropy parameters was explored for non-invasive screening of cervical precancerous alterations ex vivo, with the indication of a strong potential for clinical diagnostic purposes.

ITALICS: an algorithm for normalization and DNA copy number calling for Affymetrix SNP arrays.

PubMed

Rigaill, Guillem; Hupé, Philippe; Almeida, Anna; La Rosa, Philippe; Meyniel, Jean-Philippe; Decraene, Charles; Barillot, Emmanuel

2008-03-15

Affymetrix SNP arrays can be used to determine the DNA copy number measurement of 11 000-500 000 SNPs along the genome. Their high density facilitates the precise localization of genomic alterations and makes them a powerful tool for studies of cancers and copy number polymorphism. Like other microarray technologies it is influenced by non-relevant sources of variation, requiring correction. Moreover, the amplitude of variation induced by non-relevant effects is similar or greater than the biologically relevant effect (i.e. true copy number), making it difficult to estimate non-relevant effects accurately without including the biologically relevant effect. We addressed this problem by developing ITALICS, a normalization method that estimates both biological and non-relevant effects in an alternate, iterative manner, accurately eliminating irrelevant effects. We compared our normalization method with other existing and available methods, and found that ITALICS outperformed these methods for several in-house datasets and one public dataset. These results were validated biologically by quantitative PCR. The R package ITALICS (ITerative and Alternative normaLIzation and Copy number calling for affymetrix Snp arrays) has been submitted to Bioconductor.

Network dynamics and systems biology

NASA Astrophysics Data System (ADS)

Norrell, Johannes A.

The physics of complex systems has grown considerably as a field in recent decades, largely due to improved computational technology and increased availability of systems level data. One area in which physics is of growing relevance is molecular biology. A new field, systems biology, investigates features of biological systems as a whole, a strategy of particular importance for understanding emergent properties that result from a complex network of interactions. Due to the complicated nature of the systems under study, the physics of complex systems has a significant role to play in elucidating the collective behavior. In this dissertation, we explore three problems in the physics of complex systems, motivated in part by systems biology. The first of these concerns the applicability of Boolean models as an approximation of continuous systems. Studies of gene regulatory networks have employed both continuous and Boolean models to analyze the system dynamics, and the two have been found produce similar results in the cases analyzed. We ask whether or not Boolean models can generically reproduce the qualitative attractor dynamics of networks of continuously valued elements. Using a combination of analytical techniques and numerical simulations, we find that continuous networks exhibit two effects---an asymmetry between on and off states, and a decaying memory of events in each element's inputs---that are absent from synchronously updated Boolean models. We show that in simple loops these effects produce exactly the attractors that one would predict with an analysis of the stability of Boolean attractors, but in slightly more complicated topologies, they can destabilize solutions that are stable in the Boolean approximation, and can stabilize new attractors. Second, we investigate ensembles of large, random networks. Of particular interest is the transition between ordered and disordered dynamics, which is well characterized in Boolean systems. Networks at the transition point, called critical, exhibit many of the features of regulatory networks, and recent studies suggest that some specific regulatory networks are indeed near-critical. We ask whether certain statistical measures of the ensemble behavior of large continuous networks are reproduced by Boolean models. We find that, in spite of the lack of correspondence between attractors observed in smaller systems, the statistical characterization given by the continuous and Boolean models show close agreement, and the transition between order and disorder known in Boolean systems can occur in continuous systems as well. One effect that is not present in Boolean systems, the failure of information to propagate down chains of elements of arbitrary length, is present in a class of continuous networks. In these systems, a modified Boolean theory that takes into account the collective effect of propagation failure on chains throughout the network gives a good description of the observed behavior. We find that propagation failure pushes the system toward greater order, resulting in a partial or complete suppression of the disordered phase. Finally, we explore a dynamical process of direct biological relevance: asymmetric cell division in A. thaliana. The long term goal is to develop a model for the process that accurately accounts for both wild type and mutant behavior. To contribute to this endeavor, we use confocal microscopy to image roots in a SHORT-ROOT inducible mutant. We compute correlation functions between the locations of asymmetrically divided cells, and we construct stochastic models based on a few simple assumptions that accurately predict the non-zero correlations. Our result shows that intracellular processes alone cannot be responsible for the observed divisions, and that an intercell signaling mechanism could account for the measured correlations.

Imprinted Oxide and MIP/Oxide Hybrid Nanomaterials for Chemical Sensors †

PubMed Central

2018-01-01

The oxides of transition, post-transition and rare-earth metals have a long history of robust and fast responsive recognition elements for electronic, optical, and gravimetric devices. A wide range of applications successfully utilized pristine or doped metal oxides and polymer-oxide hybrids as nanostructured recognition elements for the detection of biologically relevant molecules, harmful organic substances, and drugs as well as for the investigative process control applications. An overview of the selected recognition applications of molecularly imprinted sol-gel phases, metal oxides and hybrid nanomaterials composed of molecularly imprinted polymers (MIP) and metal oxides is presented herein. The formation and fabrication processes for imprinted sol-gel layers, metal oxides, MIP-coated oxide nanoparticles and other MIP/oxide nanohybrids are discussed along with their applications in monitoring bioorganic analytes and processes. The sensor characteristics such as dynamic detection range and limit of detection are compared as the performance criterion and the miniaturization and commercialization possibilities are critically discussed. PMID:29677107

Imprinted Oxide and MIP/Oxide Hybrid Nanomaterials for Chemical Sensors †.

PubMed

Afzal, Adeel; Dickert, Franz L

2018-04-20

The oxides of transition, post-transition and rare-earth metals have a long history of robust and fast responsive recognition elements for electronic, optical, and gravimetric devices. A wide range of applications successfully utilized pristine or doped metal oxides and polymer-oxide hybrids as nanostructured recognition elements for the detection of biologically relevant molecules, harmful organic substances, and drugs as well as for the investigative process control applications. An overview of the selected recognition applications of molecularly imprinted sol-gel phases, metal oxides and hybrid nanomaterials composed of molecularly imprinted polymers (MIP) and metal oxides is presented herein. The formation and fabrication processes for imprinted sol-gel layers, metal oxides, MIP-coated oxide nanoparticles and other MIP/oxide nanohybrids are discussed along with their applications in monitoring bioorganic analytes and processes. The sensor characteristics such as dynamic detection range and limit of detection are compared as the performance criterion and the miniaturization and commercialization possibilities are critically discussed.

Biological forcing controls the chemistry of reef-building coral skeleton

NASA Astrophysics Data System (ADS)

Meibom, Anders; Mostefaoui, Smail; Cuif, Jean-Pierre; Dauphin, Yannicke; Houlbreque, Fanny; Dunbar, Robert; Constantz, Brent

2007-01-01

We present analyses of major elements C and Ca and trace elements N, S, Mg and Sr in a Porites sp. exoskeleton with a spatial resolution better than ˜150 nm. Trace element variations are evaluated directly against the ultra-structure of the skeleton and are ascribed to dynamic biological forcing. Individual growth layers in the bulk fibrous aragonite skeleton form on sub-daily timescales. Magnesium concentration variations are dramatically correlated with the growth layers, but are uncorrelated with Sr concentration variations. Observed (sub)seasonal relationships between water temperature and skeletal trace-element chemistry are secondary, mediated by sensitive biological processes to which classical thermodynamic formalism does not apply.

Biological toxicity of lanthanide elements on algae.

PubMed

Tai, Peidong; Zhao, Qing; Su, Dan; Li, Peijun; Stagnitti, Frank

2010-08-01

The biological toxicity of lanthanides on marine monocellular algae was investigated. The specific objective of this research was to establish the relationship between the abundance in the seawater of lanthanides and their biological toxicities on marine monocellular algae. The results showed that all single lanthanides had similar toxic effects on Skeletonema costatum. High concentrations of lanthanides (29.04+/-0.61 micromol L(-1)) resulted in 50% reduction in growth of algae compared to the controls (0 micromol L(-1)) after 96 h (96 h-EC50). The biological toxicity of 13 lanthanides on marine monocellular algae was unrelated with the abundance of different lanthanide elements in nature, and the "Harkins rule" was not appropriate for the lanthanides. A mixed solution that contained equivalent concentrations of each lanthanide element had the same inhibition effect on algae cells as each individual lanthanide element at the same total concentration. This phenomenon is unique compared to the groups of other elements in the periodic table. Hence, we speculate that the monocellular organisms might not be able to sufficiently differentiate between the almost chemically identical lanthanide elements. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Applications of synchrotron μ-XRF to study the distribution of biologically important elements in different environmental matrices: a review.

PubMed

Majumdar, Sanghamitra; Peralta-Videa, Jose R; Castillo-Michel, Hiram; Hong, Jie; Rico, Cyren M; Gardea-Torresdey, Jorge L

2012-11-28

Environmental matrices including soils, sediments, and living organisms are reservoirs of several essential as well as non-essential elements. Accurate qualitative and quantitative information on the distribution and interaction of biologically significant elements is vital to understand the role of these elements in environmental and biological samples. Synchrotron micro-X-ray fluorescence (μ-SXRF) allows in situ mapping of biologically important elements at nanometer to sub-micrometer scale with high sensitivity, negligible sample damage and enable tuning of the incident energy as desired. Beamlines in the synchrotron facilities are rapidly increasing their analytical versatility in terms of focusing optics, detector technologies, incident energy, and sample environment. Although extremely competitive, it is now feasible to find stations offering complimentary techniques like micro-X-ray diffraction (μ-XRD) and micro-X-ray absorption spectroscopy (μ-XAS) that will allow a more complete characterization of complex matrices. This review includes the most recent literature on the emerging applications and challenges of μ-SXRF in studying the distribution of biologically important elements and manufactured nanoparticles in soils, sediments, plants, and microbes. The advantages of using μ-SXRF and complimentary techniques in contrast to conventional techniques used for the respective studies are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

Synthesis and Demonstration of the Biological Relevance of sp3 -rich Scaffolds Distantly Related to Natural Product Frameworks.

PubMed

Foley, Daniel J; Craven, Philip G E; Collins, Patrick M; Doveston, Richard G; Aimon, Anthony; Talon, Romain; Churcher, Ian; von Delft, Frank; Marsden, Stephen P; Nelson, Adam

2017-10-26

The productive exploration of chemical space is an enduring challenge in chemical biology and medicinal chemistry. Natural products are biologically relevant, and their frameworks have facilitated chemical tool and drug discovery. A "top-down" synthetic approach is described that enabled a range of complex bridged intermediates to be converted with high step efficiency into 26 diverse sp 3 -rich scaffolds. The scaffolds have local natural product-like features, but are only distantly related to specific natural product frameworks. To assess biological relevance, a set of 52 fragments was prepared, and screened by high-throughput crystallography against three targets from two protein families (ATAD2, BRD1 and JMJD2D). In each case, 3D fragment hits were identified that would serve as distinctive starting points for ligand discovery. This demonstrates that frameworks that are distantly related to natural products can facilitate discovery of new biologically relevant regions within chemical space. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and Demonstration of the Biological Relevance of sp3‐rich Scaffolds Distantly Related to Natural Product Frameworks

PubMed Central

Foley, Daniel J.; Craven, Philip G. E.; Collins, Patrick M.; Doveston, Richard G.; Aimon, Anthony; Talon, Romain; Churcher, Ian; von Delft, Frank

2017-01-01

Abstract The productive exploration of chemical space is an enduring challenge in chemical biology and medicinal chemistry. Natural products are biologically relevant, and their frameworks have facilitated chemical tool and drug discovery. A “top‐down” synthetic approach is described that enabled a range of complex bridged intermediates to be converted with high step efficiency into 26 diverse sp3‐rich scaffolds. The scaffolds have local natural product‐like features, but are only distantly related to specific natural product frameworks. To assess biological relevance, a set of 52 fragments was prepared, and screened by high‐throughput crystallography against three targets from two protein families (ATAD2, BRD1 and JMJD2D). In each case, 3D fragment hits were identified that would serve as distinctive starting points for ligand discovery. This demonstrates that frameworks that are distantly related to natural products can facilitate discovery of new biologically relevant regions within chemical space. PMID:28983993

Active Learning and Student-centered Pedagogy Improve Student Attitudes and Performance in Introductory Biology

PubMed Central

Patel, Maya; Johnson, Erika; Weiss, Martha

2009-01-01

We describe the development and implementation of an instructional design that focused on bringing multiple forms of active learning and student-centered pedagogies to a one-semester, undergraduate introductory biology course for both majors and nonmajors. Our course redesign consisted of three major elements: 1) reordering the presentation of the course content in an attempt to teach specific content within the context of broad conceptual themes, 2) incorporating active and problem-based learning into every lecture, and 3) adopting strategies to create a more student-centered learning environment. Assessment of our instructional design consisted of a student survey and comparison of final exam performance across 3 years—1 year before our course redesign was implemented (2006) and during two successive years of implementation (2007 and 2008). The course restructuring led to significant improvement of self-reported student engagement and satisfaction and increased academic performance. We discuss the successes and ongoing challenges of our course restructuring and consider issues relevant to institutional change. PMID:19723815

Active medulloblastoma enhancers reveal subgroup-specific cellular origins

PubMed Central

Lin, Charles Y.; Erkek, Serap; Tong, Yiai; Yin, Linlin; Federation, Alexander J.; Zapatka, Marc; Haldipur, Parthiv; Kawauchi, Daisuke; Risch, Thomas; Warnatz, Hans-Jörg; Worst, Barbara C.; Ju, Bensheng; Orr, Brent A.; Zeid, Rhamy; Polaski, Donald R.; Segura-Wang, Maia; Waszak, Sebastian M.; Jones, David T.W.; Kool, Marcel; Hovestadt, Volker; Buchhalter, Ivo; Sieber, Laura; Johann, Pascal; Chavez, Lukas; Gröschel, Stefan; Ryzhova, Marina; Korshunov, Andrey; Chen, Wenbiao; Chizhikov, Victor V.; Millen, Kathleen J.; Amstislavskiy, Vyacheslav; Lehrach, Hans; Yaspo, Marie-Laure; Eils, Roland; Lichter, Peter; Korbel, Jan O.; Pfister, Stefan M.; Bradner, James E.; Northcott, Paul A.

2016-01-01

Summary Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking. Using H3K27ac and BRD4 ChIP-Seq, coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors, validated by ChIP-Seq, that are responsible for subgroup divergence and implicate candidate cells-of-origin for Group 4. Our integrated analysis of enhancer elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins. PMID:26814967

Evolution of colour vision in mammals.

PubMed

Jacobs, Gerald H

2009-10-12

Colour vision allows animals to reliably distinguish differences in the distributions of spectral energies reaching the eye. Although not universal, a capacity for colour vision is sufficiently widespread across the animal kingdom to provide prima facie evidence of its importance as a tool for analysing and interpreting the visual environment. The basic biological mechanisms on which vertebrate colour vision ultimately rests, the cone opsin genes and the photopigments they specify, are highly conserved. Within that constraint, however, the utilization of these basic elements varies in striking ways in that they appear, disappear and emerge in altered form during the course of evolution. These changes, along with other alterations in the visual system, have led to profound variations in the nature and salience of colour vision among the vertebrates. This article concerns the evolution of colour vision among the mammals, viewing that process in the context of relevant biological mechanisms, of variations in mammalian colour vision, and of the utility of colour vision.

Evolution of colour vision in mammals

PubMed Central

Jacobs, Gerald H.

2009-01-01

Colour vision allows animals to reliably distinguish differences in the distributions of spectral energies reaching the eye. Although not universal, a capacity for colour vision is sufficiently widespread across the animal kingdom to provide prima facie evidence of its importance as a tool for analysing and interpreting the visual environment. The basic biological mechanisms on which vertebrate colour vision ultimately rests, the cone opsin genes and the photopigments they specify, are highly conserved. Within that constraint, however, the utilization of these basic elements varies in striking ways in that they appear, disappear and emerge in altered form during the course of evolution. These changes, along with other alterations in the visual system, have led to profound variations in the nature and salience of colour vision among the vertebrates. This article concerns the evolution of colour vision among the mammals, viewing that process in the context of relevant biological mechanisms, of variations in mammalian colour vision, and of the utility of colour vision. PMID:19720656

Using novel descriptor accounting for ligand-receptor interactions to define and visually explore biologically relevant chemical space.

PubMed

Rabal, Obdulia; Oyarzabal, Julen

2012-05-25

The definition and pragmatic implementation of biologically relevant chemical space is critical in addressing navigation strategies in the overlapping regions where chemistry and therapeutically relevant targets reside and, therefore, also key to performing an efficient drug discovery project. Here, we describe the development and implementation of a simple and robust method for representing biologically relevant chemical space as a general reference according to current knowledge, independently of any reference space, and analyzing chemical structures accordingly. Underlying our method is the generation of a novel descriptor (LiRIf) that converts structural information into a one-dimensional string accounting for the plausible ligand-receptor interactions as well as for topological information. Capitalizing on ligand-receptor interactions as a descriptor enables the clustering, profiling, and comparison of libraries of compounds from a chemical biology and medicinal chemistry perspective. In addition, as a case study, R-groups analysis is performed to identify the most populated ligand-receptor interactions according to different target families (GPCR, kinases, etc.), as well as to evaluate the coverage of biologically relevant chemical space by structures annotated in different databases (ChEMBL, Glida, etc.).

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

SacconePhD, Scott F; Chesler, Elissa J; Bierut, Laura J

Commercial SNP microarrays now provide comprehensive and affordable coverage of the human genome. However, some diseases have biologically relevant genomic regions that may require additional coverage. Addiction, for example, is thought to be influenced by complex interactions among many relevant genes and pathways. We have assembled a list of 486 biologically relevant genes nominated by a panel of experts on addiction. We then added 424 genes that showed evidence of association with addiction phenotypes through mouse QTL mappings and gene co-expression analysis. We demonstrate that there are a substantial number of SNPs in these genes that are not well representedmore » by commercial SNP platforms. We address this problem by introducing a publicly available SNP database for addiction. The database is annotated using numeric prioritization scores indicating the extent of biological relevance. The scores incorporate a number of factors such as SNP/gene functional properties (including synonymy and promoter regions), data from mouse systems genetics and measures of human/mouse evolutionary conservation. We then used HapMap genotyping data to determine if a SNP is tagged by a commercial microarray through linkage disequilibrium. This combination of biological prioritization scores and LD tagging annotation will enable addiction researchers to supplement commercial SNP microarrays to ensure comprehensive coverage of biologically relevant regions.« less

Materials in Manufacturing and Packaging Systems as Sources of Elemental Impurities in Packaged Drug Products: A Literature Review.

PubMed

Jenke, Dennis R; Stults, Cheryl L M; Paskiet, Diane M; Ball, Douglas J; Nagao, Lee M

Elemental impurities in drug products can arise from a number of different sources and via a number of different means, including the active pharmaceutical ingredient, excipients, the vehicle, and leaching of elemental entities that are present in the drug product's manufacturing or packaging systems. Thus, knowledge about the presence, level, and likelihood of leaching of elemental entities in manufacturing and packaging systems is relevant to understanding how these systems contribute to a drug product's total elemental impurity burden. To that end, a joint team from the Extractables and Leachables Safety Information Exchange (ELSIE) Consortium and the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) has conducted a review of the available literature on elemental entities in pharmaceutically relevant polymers and the presence of these elemental entities in material extracts and/or drug products. This review article contains the information compiled from the available body of literature and considers two questions: (1) What elemental entities are present in the relevant polymers and materials and at what levels are they present? (2) To what extent are these elemental entities leached from these materials under conditions relevant to the manufacturing and storage/distribution of solution drug products? Conclusions drawn from the compiled data are as follows: (1) Elemental entities are present in the materials used to construct packaging and manufacturing systems as these materials either contain these elemental entities as additives or are exposed to elemental entities during their production. (2) Unless the elemental entities are parts of the materials themselves (for example, SiO 2 in glass) or intentionally added to the materials (for example, metal stearates in polymers), their incidental amounts in the materials are generally low. (3) When elemental entities are present in materials and systems, generally only a very small fraction of the total available amount of the entity can be leached under conditions that are relevant to packaged drug products. Thus, while sources of certain elemental impurities may be ubiquitous in the natural environment, they are not ubiquitous in materials used in pharmaceutical packaging and manufacturing systems and when they are present, they are not extensively leached under relevant conditions. The information summarized here can be utilized to aid the elemental impurity risk assessment process by providing the identities of commonly reported elements and data to support probability estimates of those becoming elemental impurities in the drug product. Furthermore, recommendations are made related to establishing elements of potential product impact for individual materials. Extraneous impurities in drug products provide no therapeutic benefit and thus should be known and controlled. Elemental impurities can arise from a number of sources and by a number of means, including the leaching of elemental entities from drug product packaging and manufacturing systems. To understand the extent to which materials used in packaging systems contain elemental entities and the extent to which those entities leach into drug products to become elemental impurities, the Extractables and Leachables Safety Information Exchange (ELSIE) and International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) Consortia have jointly performed a literature review on this subject. Using the compiled information, it was concluded that while packaging materials may contain elemental entities, unless those entities are intentional parts of the materials, the amounts of those elemental entities are generally low. Furthermore, generally only a very small fraction of the total available amount of the entity can be leached under conditions that are relevant to packaged drug products. Thus, risk assessment of sources of elemental impurities in drug products that may be related to materials used in pharmaceutical packaging and manufacturing systems can utilize the information and recommendations presented here. © PDA, Inc. 2015.

Methods for Improving the Curvature of Steerable Needles in Biological Tissue

PubMed Central

Adebar, Troy K.; Greer, Joseph D.; Laeseke, Paul F.; Hwang, Gloria L.; Okamura, Allison M.

2016-01-01

Robotic needle steering systems have the potential to improve percutaneous interventions such as radiofrequency ablation of liver tumors, but steering techniques described to date have not achieved sufficiently small radius of curvature in biological tissue to be relevant to this application. In this work, the impact of tip geometry on steerable needle curvature is examined. Finite-element simulations and experiments with bent-tip needles in ex vivo liver tissue demonstrate that selection of tip length and angle can greatly improve curvature, with radius of curvature below 5 cm in liver tissue possible through judicious selection of these parameters. Motivated by the results of this analysis, a new articulated-tip steerable needle is described, in which a distal section is actively switched by a robotic system between a straight tip (resulting in a straight path) and a bent tip (resulting in a curved path). This approach allows the tip length and angle to be increased, while the straight configuration allows the needle tip to still pass through an introducer sheath and rotate inside the body. Validation testing in liver tissue shows that the new articulated-tip steerable needle achieves smaller radius of curvature compared to bent-tip needles described in previous work. Steerable needles with optimized tip parameters, which can generate tight curves in liver tissue, increase the clinical relevance of needle steering to percutaneous interventions. PMID:26441438

Shaping intercellular channels of plasmodesmata: the structure-to-function missing link.

PubMed

Nicolas, William J; Grison, Magali S; Bayer, Emmanuelle M

2017-12-18

Plasmodesmata (PD) are a hallmark of the plant kingdom and a cornerstone of plant biology and physiology, forming the conduits for the cell-to-cell transfer of proteins, RNA and various metabolites, including hormones. They connect the cytosols and endomembranes of cells, which allows enhanced cell-to-cell communication and synchronization. Because of their unique position as intercellular gateways, they are at the frontline of plant defence and signalling and constitute the battleground for virus replication and spreading. The membranous organization of PD is remarkable, where a tightly furled strand of endoplasmic reticulum comes into close apposition with the plasma membrane, the two connected by spoke-like elements. The role of these structural features is, to date, still not completely understood. Recent data on PD seem to point in an unexpected direction, establishing a close parallel between PD and membrane contact sites and defining plasmodesmal membranes as microdomains. However, the implications of this new viewpoint are not fully understood. Aided by available phylogenetic data, this review attempts to reassess the function of the different elements comprising the PD and the relevance of membrane lipid composition and biophysics in defining specialized microdomains of PD, critical for their function. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Aquaporins Mediate Silicon Transport in Humans

PubMed Central

Garneau, Alexandre P.; Carpentier, Gabriel A.; Marcoux, Andrée-Anne; Frenette-Cotton, Rachelle; Simard, Charles F.; Rémus-Borel, Wilfried; Caron, Luc; Jacob-Wagner, Mariève; Noël, Micheline; Powell, Jonathan J.; Bélanger, Richard; Côté, François; Isenring, Paul

2015-01-01

In animals, silicon is an abundant and differentially distributed trace element that is believed to play important biological functions. One would thus expect silicon concentrations in body fluids to be regulated by silicon transporters at the surface of many cell types. Curiously, however, and even though they exist in plants and algae, no such transporters have been identified to date in vertebrates. Here, we show for the first time that the human aquaglyceroporins, i.e., AQP3, AQP7, AQP9 and AQP10 can act as silicon transporters in both Xenopus laevis oocytes and HEK-293 cells. In particular, heterologously expressed AQP7, AQP9 and AQP10 are all able to induce robust, saturable, phloretin-sensitive silicon transport activity in the range that was observed for low silicon rice 1 (lsi1), a silicon transporter in plant. Furthermore, we show that the aquaglyceroporins appear as relevant silicon permeation pathways in both mice and humans based on 1) the kinetics of substrate transport, 2) their presence in tissues where silicon is presumed to play key roles and 3) their transcriptional responses to changes in dietary silicon. Taken together, our data provide new evidence that silicon is a potentially important biological element in animals and that its body distribution is regulated. They should open up original areas of investigations aimed at deciphering the true physiological role of silicon in vertebrates. PMID:26313002

Aquaporins Mediate Silicon Transport in Humans.

PubMed

Garneau, Alexandre P; Carpentier, Gabriel A; Marcoux, Andrée-Anne; Frenette-Cotton, Rachelle; Simard, Charles F; Rémus-Borel, Wilfried; Caron, Luc; Jacob-Wagner, Mariève; Noël, Micheline; Powell, Jonathan J; Bélanger, Richard; Côté, François; Isenring, Paul

2015-01-01

In animals, silicon is an abundant and differentially distributed trace element that is believed to play important biological functions. One would thus expect silicon concentrations in body fluids to be regulated by silicon transporters at the surface of many cell types. Curiously, however, and even though they exist in plants and algae, no such transporters have been identified to date in vertebrates. Here, we show for the first time that the human aquaglyceroporins, i.e., AQP3, AQP7, AQP9 and AQP10 can act as silicon transporters in both Xenopus laevis oocytes and HEK-293 cells. In particular, heterologously expressed AQP7, AQP9 and AQP10 are all able to induce robust, saturable, phloretin-sensitive silicon transport activity in the range that was observed for low silicon rice 1 (lsi1), a silicon transporter in plant. Furthermore, we show that the aquaglyceroporins appear as relevant silicon permeation pathways in both mice and humans based on 1) the kinetics of substrate transport, 2) their presence in tissues where silicon is presumed to play key roles and 3) their transcriptional responses to changes in dietary silicon. Taken together, our data provide new evidence that silicon is a potentially important biological element in animals and that its body distribution is regulated. They should open up original areas of investigations aimed at deciphering the true physiological role of silicon in vertebrates.

Nutritional Systems Biology Modeling: From Molecular Mechanisms to Physiology

PubMed Central

de Graaf, Albert A.; Freidig, Andreas P.; De Roos, Baukje; Jamshidi, Neema; Heinemann, Matthias; Rullmann, Johan A.C.; Hall, Kevin D.; Adiels, Martin; van Ommen, Ben

2009-01-01

The use of computational modeling and simulation has increased in many biological fields, but despite their potential these techniques are only marginally applied in nutritional sciences. Nevertheless, recent applications of modeling have been instrumental in answering important nutritional questions from the cellular up to the physiological levels. Capturing the complexity of today's important nutritional research questions poses a challenge for modeling to become truly integrative in the consideration and interpretation of experimental data at widely differing scales of space and time. In this review, we discuss a selection of available modeling approaches and applications relevant for nutrition. We then put these models into perspective by categorizing them according to their space and time domain. Through this categorization process, we identified a dearth of models that consider processes occurring between the microscopic and macroscopic scale. We propose a “middle-out” strategy to develop the required full-scale, multilevel computational models. Exhaustive and accurate phenotyping, the use of the virtual patient concept, and the development of biomarkers from “-omics” signatures are identified as key elements of a successful systems biology modeling approach in nutrition research—one that integrates physiological mechanisms and data at multiple space and time scales. PMID:19956660

An Undergraduate Course to Bridge the Gap between Textbooks and Scientific Research

PubMed Central

Wiegant, Fred; Scager, Karin; Boonstra, Johannes

2011-01-01

This article reports on a one-semester Advanced Cell Biology course that endeavors to bridge the gap between gaining basic textbook knowledge about cell biology and learning to think and work as a researcher. The key elements of this course are 1) learning to work with primary articles in order to get acquainted with the field of choice, to learn scientific reasoning, and to identify gaps in our current knowledge that represent opportunities for further research; 2) formulating a research project with fellow students; 3) gaining thorough knowledge of relevant methodology and technologies used within the field of cell biology; 4) developing cooperation and leadership skills; and 5) presenting and defending research projects before a jury of experts. The course activities were student centered and focused on designing a genuine research program. Our 5-yr experience with this course demonstrates that 1) undergraduate students are capable of delivering high-quality research designs that meet professional standards, and 2) the authenticity of the learning environment in this course strongly engages students to become self-directed and critical thinkers. We hope to provide colleagues with an example of a course that encourages and stimulates students to develop essential research thinking skills. PMID:21364103

Exact solutions of a two parameter flux model and cryobiological applications.

PubMed

Benson, James D; Chicone, Carmen C; Critser, John K

2005-06-01

Solute-solvent transmembrane flux models are used throughout biological sciences with applications in plant biology, cryobiology (transplantation and transfusion medicine), as well as circulatory and kidney physiology. Using a standard two parameter differential equation model of solute and solvent transmembrane flux described by Jacobs [The simultaneous measurement of cell permeability to water and to dissolved substances, J. Cell. Comp. Physiol. 2 (1932) 427-444], we determine the functions that describe the intracellular water volume and moles of intracellular solute for every time t and every set of initial conditions. Here, we provide several novel biophysical applications of this theory to important biological problems. These include using this result to calculate the value of cell volume excursion maxima and minima along with the time at which they occur, a novel result that is of significant relevance to the addition and removal of permeating solutes during cryopreservation. We also present a methodology that produces extremely accurate sum of squares estimates when fitting data for cellular permeability parameter values. Finally, we show that this theory allows a significant increase in both accuracy and speed of finite element methods for multicellular volume simulations, which has critical clinical biophysical applications in cryosurgical approaches to cancer treatment.

Using nuclear microscopy to characterize the interaction of textile-used silver nanoparticles with a biological wastewater treatment system

NASA Astrophysics Data System (ADS)

Bento, J. B.; Franca, R. D. G.; Pinheiro, T.; Alves, L. C.; Pinheiro, H. M.; Lourenço, N. D.

2017-08-01

The use of engineered nanoparticles in the textile industry has been rapidly increasing but their fate during biological wastewater treatment is largely unknown. The goal of the current study was to characterize the interaction of silver nanoparticles (AgNPs), used in the textile industry, with a biological wastewater treatment system based on aerobic granular sludge (AGS). The exposure tests were performed using a laboratory-scale sequencing batch reactor (SBR) system with AGS. The behavior and fate of textile AgNPs in the AGS system was studied with nuclear microscopy techniques. Elemental maps of AGS samples collected from the SBR showed that AgNPs typically clustered in agglomerates of small dimensions (<10 μm), which were preferentially associated with extracellular polymeric substances (EPS). This preliminary study highlights the potential application of nuclear microscopy for the characterization of the behavior and fate of AgNPs in AGS. The detailed compartmentalization of AgNPs in AGS components obtained with nuclear microscopy provides new and relevant information concerning AgNPs retention. This will be important in biotechnological terms to delineate strategies for AgNPs removal from textile wastewater.

An undergraduate course to bridge the gap between textbooks and scientific research.

PubMed

Wiegant, Fred; Scager, Karin; Boonstra, Johannes

2011-01-01

This article reports on a one-semester Advanced Cell Biology course that endeavors to bridge the gap between gaining basic textbook knowledge about cell biology and learning to think and work as a researcher. The key elements of this course are 1) learning to work with primary articles in order to get acquainted with the field of choice, to learn scientific reasoning, and to identify gaps in our current knowledge that represent opportunities for further research; 2) formulating a research project with fellow students; 3) gaining thorough knowledge of relevant methodology and technologies used within the field of cell biology; 4) developing cooperation and leadership skills; and 5) presenting and defending research projects before a jury of experts. The course activities were student centered and focused on designing a genuine research program. Our 5-yr experience with this course demonstrates that 1) undergraduate students are capable of delivering high-quality research designs that meet professional standards, and 2) the authenticity of the learning environment in this course strongly engages students to become self-directed and critical thinkers. We hope to provide colleagues with an example of a course that encourages and stimulates students to develop essential research thinking skills.

Challenges of biological sample preparation for SIMS imaging of elements and molecules at subcellular resolution

NASA Astrophysics Data System (ADS)

Chandra, Subhash

2008-12-01

Secondary ion mass spectrometry (SIMS) based imaging techniques capable of subcellular resolution characterization of elements and molecules are becoming valuable tools in many areas of biology and medicine. Due to high vacuum requirements of SIMS, the live cells cannot be analyzed directly in the instrument. The sample preparation, therefore, plays a critical role in preserving the native chemical composition for SIMS analysis. This work focuses on the evaluation of frozen-hydrated and frozen freeze-dried sample preparations for SIMS studies of cultured cells with a CAMECA IMS-3f dynamic SIMS ion microscope instrument capable of producing SIMS images with a spatial resolution of 500 nm. The sandwich freeze-fracture method was used for fracturing the cells. The complimentary fracture planes in the plasma membrane were characterized by field-emission secondary electron microscopy (FESEM) in the frozen-hydrated state. The cells fractured at the dorsal surface were used for SIMS analysis. The frozen-hydrated SIMS analysis of individual cells under dynamic primary ion beam (O 2+) revealed local secondary ion signal enhancements correlated with the water image signals of 19(H 3O) +. A preferential removal of water from the frozen cell matrix in the Z-axis was also observed. These complications render the frozen-hydrated sample type less desirable for subcellular dynamic SIMS studies. The freeze-drying of frozen-hydrated cells, either inside the instrument or externally in a freeze-drier, allowed SIMS imaging of subcellular chemical composition. Morphological evaluations of fractured freeze-dried cells with SEM and confocal laser scanning microscopy (CLSM) revealed well-preserved mitochondria, Golgi apparatus, and stress fibers. SIMS analysis of fractured freeze-dried cells revealed well-preserved chemical composition of even the most highly diffusible ions like K + and Na + in physiologically relevant concentrations. The high K-low Na signature in individual cells provided a rule-of-thumb criterion for the validation of sample preparation. The fractured freeze-dried cells allowed 3-D SIMS imaging and localization of 13C 15N labeled molecules and therapeutic drugs containing an elemental tag. Examples are shown to demonstrate that both diffusible elements and molecules are prone to artifact-induced relocation at subcellular scale if the sample preparation is compromised. The sample preparation is problem dependent and may vary widely between the diverse sample types of biological systems and the type of instrument used for SIMS analysis. The sample preparation, however, must be validated so that SIMS can be applied with confidence in biology and medicine.

An in-depth evaluation of accuracy and precision in Hg isotopic analysis via pneumatic nebulization and cold vapor generation multi-collector ICP-mass spectrometry.

PubMed

Rua-Ibarz, Ana; Bolea-Fernandez, Eduardo; Vanhaecke, Frank

2016-01-01

Mercury (Hg) isotopic analysis via multi-collector inductively coupled plasma (ICP)-mass spectrometry (MC-ICP-MS) can provide relevant biogeochemical information by revealing sources, pathways, and sinks of this highly toxic metal. In this work, the capabilities and limitations of two different sample introduction systems, based on pneumatic nebulization (PN) and cold vapor generation (CVG), respectively, were evaluated in the context of Hg isotopic analysis via MC-ICP-MS. The effect of (i) instrument settings and acquisition parameters, (ii) concentration of analyte element (Hg), and internal standard (Tl)-used for mass discrimination correction purposes-and (iii) different mass bias correction approaches on the accuracy and precision of Hg isotope ratio results was evaluated. The extent and stability of mass bias were assessed in a long-term study (18 months, n = 250), demonstrating a precision ≤0.006% relative standard deviation (RSD). CVG-MC-ICP-MS showed an approximately 20-fold enhancement in Hg signal intensity compared with PN-MC-ICP-MS. For CVG-MC-ICP-MS, the mass bias induced by instrumental mass discrimination was accurately corrected for by using either external correction in a sample-standard bracketing approach (SSB) or double correction, consisting of the use of Tl as internal standard in a revised version of the Russell law (Baxter approach), followed by SSB. Concomitant matrix elements did not affect CVG-ICP-MS results. Neither with PN, nor with CVG, any evidence for mass-independent discrimination effects in the instrument was observed within the experimental precision obtained. CVG-MC-ICP-MS was finally used for Hg isotopic analysis of reference materials (RMs) of relevant environmental origin. The isotopic composition of Hg in RMs of marine biological origin testified of mass-independent fractionation that affected the odd-numbered Hg isotopes. While older RMs were used for validation purposes, novel Hg isotopic data are provided for the latest generations of some biological RMs.

Imaging and elemental mapping of biological specimens with a dual-EDS dedicated scanning transmission electron microscope

PubMed Central

Wu, J.S.; Kim, A. M.; Bleher, R.; Myers, B.D.; Marvin, R. G.; Inada, H.; Nakamura, K.; Zhang, X.F.; Roth, E.; Li, S.Y.; Woodruff, T. K.; O'Halloran, T. V.; Dravid, Vinayak P.

2013-01-01

A dedicated analytical scanning transmission electron microscope (STEM) with dual energy dispersive spectroscopy (EDS) detectors has been designed for complementary high performance imaging as well as high sensitivity elemental analysis and mapping of biological structures. The performance of this new design, based on a Hitachi HD-2300A model, was evaluated using a variety of biological specimens. With three imaging detectors, both the surface and internal structure of cells can be examined simultaneously. The whole-cell elemental mapping, especially of heavier metal species that have low cross-section for electron energy loss spectroscopy (EELS), can be faithfully obtained. Optimization of STEM imaging conditions is applied to thick sections as well as thin sections of biological cells under low-dose conditions at room- and cryogenic temperatures. Such multimodal capabilities applied to soft/biological structures usher a new era for analytical studies in biological systems. PMID:23500508

Investigation of micrometre-sized fossil by laser mass spectrometer (LMS) designed for in situ space research

NASA Astrophysics Data System (ADS)

Tulej, Marek; Neubeck, Anna; Ivarsson, Magnus; Brigitte Neuland, Maike; Riedo, Andreas; Wurz, Peter

2015-04-01

Search for signatures of life on other planets is one of the most important goals of current planetary missions. Among various possible biomarkers, which can be investigated in situ on planetary surfaces, the detection of bio-relevant elements in planetary materials is of considerable interest and the abundance of isotopes can be important signatures of past and present bioactivities [1, 2]. We investigate the chemical composition of fossilised biological inclusions embedded in a carbonate host phase by a miniature laser ablation mass spectrometer (LMS) [3]. The LMS instrument combines a laser ablation ion source for ablation, atomisation and ionisation of surface material with a reflectron time-of-flight (TOF) mass spectrometer. LMS delivers mass spectra of almost all elements and their isotopes. In the current setup a fs-laser ablation ion source is applied with high lateral (15 um) and vertical (sub-um) resolution [4, 7] and the mass analyser supports mass resolution of 400-500 (at 56Fe mass peak) and dynamic range of eight orders of magnitude [5, 6]. From the 200 mass spectra recorded at 200 different locations on the carbonate sample surface, five mass spectra were identified which recorded the chemical composition of inclusions; from the other mass spectra the composition of the carbonate host matrix could be determined. The microscopic inspection of the sample surface and correlation with the coordinates of the laser ablation measurements made the confirmation to the location of the inclusion [8]. For the carbonate host matrix, the mass spectrometric analysis yielded the major elements H, C, O, Na, Mg, K and Ca and the trace elements Li, B and Cl. The measurements at the inclusion locations yielded in addition, the detection of F, Si, P, S, Mn, Fe, Ni, Co and Se. For most of the major elements the isotope ratios were found to be conform to the terrestrial values within a few per mills, while for minor and trace elements the determination of isotope ratios were less accurate due to low signal to noise ratios (SNR). The isotope abundances for the lightest isotope of B, S were observed to be larger than terrestrial, which is consistent with isotope fractionation by bio-relevant processes and a salty ocean. The studies demonstrates the current performance of the miniature LMS for in situ investigation of highly heterogeneous samples and its capabilities for the identification of fossilised biological matter. References: [1] Summons et al., Astrobiology, 11, 157, 2011. [2] Wurz et al., Sol. Sys. Res. 46 408, 2012. [3] Rohner et al.,Meas. Sci. Technol., 14, 2159, 2003. [4] Riedo et al., J. Anal. Atom. Spectrom. 28, 1256, 2013. [5] Riedo et al., J. Mass Spectrom.48, 1, 2013. [6] Neuland et al., Planet. Space. Sci. 101, 196, 2014. [7] Grimaudo et al., Anal. Chem. 2014, submitted. [8] Tulej et al. Geostand. Geoanal. Res., 2014; DOI: 10.1111/j.1751-908X.2014.00302.x

Biological relevance of streamflow metrics: Regional and national perspectives

USGS Publications Warehouse

Carlisle, Daren M.; Grantham, Theodore E.; Eng, Kenny; Wolock, David M.

2017-01-01

Protecting the health of streams and rivers requires identifying ecologically significant attributes of the natural flow regime. Streamflow regimes are routinely quantified using a plethora of hydrologic metrics (HMs), most of which have unknown relevance to biological communities. At regional and national scales, we evaluated which of 509 commonly used HMs were associated with biological indicators of fish and invertebrate community integrity. We quantified alteration of each HM by using statistical models to predict site-specific natural baseline values for each of 728 sites across the USA where streamflow monitoring data were available concurrent with assessments of invertebrate or fish community integrity. We then ranked HMs according to their individual association with biological integrity based on random forest models that included HMs and other relevant covariates, such as land cover and stream chemistry. HMs were generally the most important predictors of biological integrity relative to the covariates. At a national scale, the most influential HMs were measures of depleted high flows, homogenization of flows, and erratic flows. Unique combinations of biologically relevant HMs were apparent among regions. We discuss the implications of our findings to the challenge of selecting HMs for streamflow research and management.

Statistical approach for selection of biologically informative genes.

PubMed

Das, Samarendra; Rai, Anil; Mishra, D C; Rai, Shesh N

2018-05-20

Selection of informative genes from high dimensional gene expression data has emerged as an important research area in genomics. Many gene selection techniques have been proposed so far are either based on relevancy or redundancy measure. Further, the performance of these techniques has been adjudged through post selection classification accuracy computed through a classifier using the selected genes. This performance metric may be statistically sound but may not be biologically relevant. A statistical approach, i.e. Boot-MRMR, was proposed based on a composite measure of maximum relevance and minimum redundancy, which is both statistically sound and biologically relevant for informative gene selection. For comparative evaluation of the proposed approach, we developed two biological sufficient criteria, i.e. Gene Set Enrichment with QTL (GSEQ) and biological similarity score based on Gene Ontology (GO). Further, a systematic and rigorous evaluation of the proposed technique with 12 existing gene selection techniques was carried out using five gene expression datasets. This evaluation was based on a broad spectrum of statistically sound (e.g. subject classification) and biological relevant (based on QTL and GO) criteria under a multiple criteria decision-making framework. The performance analysis showed that the proposed technique selects informative genes which are more biologically relevant. The proposed technique is also found to be quite competitive with the existing techniques with respect to subject classification and computational time. Our results also showed that under the multiple criteria decision-making setup, the proposed technique is best for informative gene selection over the available alternatives. Based on the proposed approach, an R Package, i.e. BootMRMR has been developed and available at https://cran.r-project.org/web/packages/BootMRMR. This study will provide a practical guide to select statistical techniques for selecting informative genes from high dimensional expression data for breeding and system biology studies. Published by Elsevier B.V.

[Students in Training to Become Biology Teachers - a controlled phase II trial (NCT01567267)].

PubMed

Matic-Strametz, Mirjana; Strametz, Reinhard; Bohrt, Kevin; Ochsendorf, Falk; Weberschock, Tobias

2013-01-01

Consumers increasingly demand to take part in healthcare decisions as described by the concept of shared decision making. In order to ensure this happens the patient must be able to critically appraise the healthcare information provided, which is called critical health literacy. Critical health literacy can be taught to patients at the onset of their disease to enable them to obtain information about interventions and alternatives. For the primary prevention of common diseases like hypertension or diabetes mellitus, though, it is necessary to empower consumers to critically appraise medical information since this information is routinely presented in the mass media. This might be achieved through educational intervention programmes at school. The study was designed as a prospective controlled trial with students in training to become biology teachers at Siegen University (Germany). The intervention group received a short-term educational intervention (24 units) in human biology based on the principles of Evidence-based Medicine (EbM) and Good Scientific Practice (GSP) combined with elements of problem-based learning. The control group received a short-term intervention in human biology of equal duration, but without the elements of EbM and GSP. Knowledge and skills were evaluated by validated questionnaires and case studies in a pre-, interim, and post-interventional test in both groups. In addition, biology trainee teachers in the intervention group also planned and conducted a one-hour problem-based learning session with high school students, which was evaluated by video. The increase in knowledge (7.9±3.8 points vs. 2.7±2.5 points, p≤0.001) and appraisal skills (24.1±6.7 points vs. 14.6±6.3, p≤0.001) after the intervention was relevant and significant compared to baseline results and also compared to the control group that did not show any significant progress in knowledge (3.9±2.4 points vs. 2.7±1.7) and appraisal skills (16.2±5.9 points vs. 14.4±5.6). All the participants in the intervention group passed both the preparation and the conduction of their problem-based learning session with high school students with at least 50 % of the maximum number of points. Satisfaction among students in training to become biology teachers (median grade of 2 [good] in the German grading system) and students (89 % of students agreed this to be an interesting method) were high in the intervention group. This preliminary study showed a relevant increase in knowledge about EbM and skills in critically appraising interventional studies. Participating students were able to conduct problem-based learning sessions for high school students about the principles of EbM and GSP. The results justify a larger randomised controlled trial to evaluate both effects and applicability to different school settings. Copyright © 2012. Published by Elsevier GmbH.

A quantitative weight of evidence methodology for the assessment of reproductive and developmental toxicity and its application for classification and labeling of chemicals.

PubMed

Dekant, Wolfgang; Bridges, James

2016-12-01

Hazard assessment of chemicals usually applies narrative assessments with a number of weaknesses. Therefore, application of weight of evidence (WoE) approaches are often mandated but guidance to perform a WoE assessment is lacking. This manuscript describes a quantitative WoE (QWoE) assessment for reproductive toxicity data and its application for classification and labeling (C&L). Because C&L criteria are based on animal studies, the scope is restricted to animal toxicity data. The QWoE methodology utilizes numerical scoring sheets to assess reliability of a publication and the toxicological relevance of reported effects. Scores are given for fourteen quality aspects, best practice receives the highest score. The relevance/effects scores (0 to four) are adjusted to the key elements of the toxic response for the endpoint and include weighting factors for effects on different levels of the biological organization. The relevance/effects scores are then assessed against the criteria dose-response, magnitude and persistence of effects, consistency of observations with the hypothesis, and relation of effects to human disease. The quality/reliability scores and the relevance/effect scores are then multiplied to give a numerical strength of evidence for adverse effects. This total score is then used to assign the chemical to the different classes employed in classification. Copyright © 2016 Elsevier Inc. All rights reserved.

The Review of Nuclear Microscopy Techniques: An Approach for Nondestructive Trace Elemental Analysis and Mapping of Biological Materials.

PubMed

Mulware, Stephen Juma

2015-01-01

The properties of many biological materials often depend on the spatial distribution and concentration of the trace elements present in a matrix. Scientists have over the years tried various techniques including classical physical and chemical analyzing techniques each with relative level of accuracy. However, with the development of spatially sensitive submicron beams, the nuclear microprobe techniques using focused proton beams for the elemental analysis of biological materials have yielded significant success. In this paper, the basic principles of the commonly used microprobe techniques of STIM, RBS, and PIXE for trace elemental analysis are discussed. The details for sample preparation, the detection, and data collection and analysis are discussed. Finally, an application of the techniques to analysis of corn roots for elemental distribution and concentration is presented.

Privileged structures: efficient chemical "navigators" toward unexplored biologically relevant chemical spaces.

PubMed

Kim, Jonghoon; Kim, Heejun; Park, Seung Bum

2014-10-22

In the search for new therapeutic agents for currently incurable diseases, attention has turned to traditionally "undruggable" targets, and collections of drug-like small molecules with high diversity and quality have become a prerequisite for new breakthroughs. To generate such collections, the diversity-oriented synthesis (DOS) strategy was developed, which aims to populate new chemical space with drug-like compounds containing a high degree of molecular diversity. The resulting DOS-derived libraries have been of great value for the discovery of various bioactive small molecules and therapeutic agents, and thus DOS has emerged as an essential tool in chemical biology and drug discovery. However, the key challenge has become how to design and synthesize drug-like small-molecule libraries with improved biological relevancy as well as maximum molecular diversity. This Perspective presents the development of privileged substructure-based DOS (pDOS), an efficient strategy for the construction of polyheterocyclic compound libraries with high biological relevancy. We envisioned the specific interaction of drug-like small molecules with certain biopolymers via the incorporation of privileged substructures into polyheterocyclic core skeletons. The importance of privileged substructures such as benzopyran, pyrimidine, and oxopiperazine in rigid skeletons was clearly demonstrated through the discovery of bioactive small molecules and the subsequent identification of appropriate target biomolecule using a method called "fluorescence difference in two-dimensional gel electrophoresis". Focusing on examples of pDOS-derived bioactive compounds with exceptional specificity, we discuss the capability of privileged structures to serve as chemical "navigators" toward biologically relevant chemical spaces. We also provide an outlook on chemical biology research and drug discovery using biologically relevant compound libraries constructed by pDOS, biology-oriented synthesis, or natural product-inspired DOS.

The analytical calibration in (bio)imaging/mapping of the metallic elements in biological samples--definitions, nomenclature and strategies: state of the art.

PubMed

Jurowski, Kamil; Buszewski, Bogusław; Piekoszewski, Wojciech

2015-01-01

Nowadays, studies related to the distribution of metallic elements in biological samples are one of the most important issues. There are many articles dedicated to specific analytical atomic spectrometry techniques used for mapping/(bio)imaging the metallic elements in various kinds of biological samples. However, in such literature, there is a lack of articles dedicated to reviewing calibration strategies, and their problems, nomenclature, definitions, ways and methods used to obtain quantitative distribution maps. The aim of this article was to characterize the analytical calibration in the (bio)imaging/mapping of the metallic elements in biological samples including (1) nomenclature; (2) definitions, and (3) selected and sophisticated, examples of calibration strategies with analytical calibration procedures applied in the different analytical methods currently used to study an element's distribution in biological samples/materials such as LA ICP-MS, SIMS, EDS, XRF and others. The main emphasis was placed on the procedures and methodology of the analytical calibration strategy. Additionally, the aim of this work is to systematize the nomenclature for the calibration terms: analytical calibration, analytical calibration method, analytical calibration procedure and analytical calibration strategy. The authors also want to popularize the division of calibration methods that are different than those hitherto used. This article is the first work in literature that refers to and emphasizes many different and complex aspects of analytical calibration problems in studies related to (bio)imaging/mapping metallic elements in different kinds of biological samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Critical elements in the development of cell therapy potency assays for ischemic conditions.

PubMed

Porat, Yael; Abraham, Eytan; Karnieli, Ohad; Nahum, Sagi; Woda, Juliana; Zylberberg, Claudia

2015-07-01

A successful potency assay for a cell therapy product (CTP) used in the treatment of ischemic conditions should quantitatively measure relevant biological properties that predict therapeutic activity. This is especially challenging because of numerous degrees of complexity stemming from factors that include a multifactorial complex mechanism of action, cell source, inherent cell characteristics, culture method, administration mode and the in vivo conditions to which the cells are exposed. The expected biological function of a CTP encompasses complex interactions that range from a biochemical, metabolic or immunological activity to structural replacement of damaged tissue or organ. Therefore, the requirements for full characterization of the active substance with respect to biological function could be taxing. Moreover, the specific mechanism of action is often difficult to pinpoint to a specific molecular entity; rather, it is more dependent on the functionality of the cellular components acting in a in a multifactorial fashion. In the case of ischemic conditions, the cell therapy mechanism of action can vary from angiogenesis, vasculogenesis and arteriogenesis that may activate different pathways and clinical outcomes. The CTP cellular attributes with relation to the suggested mechanism of action can be used for the development of quantitative and reproducible analytical potency assays. CTPs selected and released on the basis of such potency assays should have the highest probability of providing meaningful clinical benefit for patients. This White Paper will discuss and give examples for key elements in the development of a potency assay for treatment of ischemic disorders treated by the use of CTPs. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

PORTAAL: A Classroom Observation Tool Assessing Evidence-Based Teaching Practices for Active Learning in Large Science, Technology, Engineering, and Mathematics Classes.

PubMed

Eddy, Sarah L; Converse, Mercedes; Wenderoth, Mary Pat

2015-01-01

There is extensive evidence that active learning works better than a completely passive lecture. Despite this evidence, adoption of these evidence-based teaching practices remains low. In this paper, we offer one tool to help faculty members implement active learning. This tool identifies 21 readily implemented elements that have been shown to increase student outcomes related to achievement, logic development, or other relevant learning goals with college-age students. Thus, this tool both clarifies the research-supported elements of best practices for instructor implementation of active learning in the classroom setting and measures instructors' alignment with these practices. We describe how we reviewed the discipline-based education research literature to identify best practices in active learning for adult learners in the classroom and used these results to develop an observation tool (Practical Observation Rubric To Assess Active Learning, or PORTAAL) that documents the extent to which instructors incorporate these practices into their classrooms. We then use PORTAAL to explore the classroom practices of 25 introductory biology instructors who employ some form of active learning. Overall, PORTAAL documents how well aligned classrooms are with research-supported best practices for active learning and provides specific feedback and guidance to instructors to allow them to identify what they do well and what could be improved. © 2015 S. L. Eddy et al. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

HUMAN BIOMONITORING TO LINK ENVIRONMENTAL EXPOSURE TO BIOLOGICALLY RELEVANT DOSE

EPA Science Inventory

The abstract and presentation on Human Biomonitoring to Link Environmental Exposure to Biologically Relevant Dose describes the use of biomarkers of exposure, biomarkers of current health state, and biomarker measurements. The abstract and presentation focuses on how biomarkers ...

Mobile element biology – new possibilities with high-throughput sequencing

PubMed Central

Xing, Jinchuan; Witherspoon, David J.; Jorde, Lynn B.

2014-01-01

Mobile elements compose more than half of the human genome, but until recently their large-scale detection was time-consuming and challenging. With the development of new high-throughput sequencing technologies, the complete spectrum of mobile element variation in humans can now be identified and analyzed. Thousands of new mobile element insertions have been discovered, yielding new insights into mobile element biology, evolution, and genomic variation. We review several high-throughput methods, with an emphasis on techniques that specifically target mobile element insertions in humans, and we highlight recent applications of these methods in evolutionary studies and in the analysis of somatic alterations in human cancers. PMID:23312846

Statistical mechanics of the Huxley-Simmons model

NASA Astrophysics Data System (ADS)

Caruel, M.; Truskinovsky, L.

2016-06-01

The chemomechanical model of Huxley and Simmons (HS) [A. F. Huxley and R. M. Simmons, Nature 233, 533 (1971), 10.1038/233533a0] provides a paradigmatic description of mechanically induced collective conformational changes relevant in a variety of biological contexts, from muscles power stroke and hair cell gating to integrin binding and hairpin unzipping. We develop a statistical mechanical perspective on the HS model by exploiting a formal analogy with a paramagnetic Ising model. We first study the equilibrium HS model with a finite number of elements and compute explicitly its mechanical and thermal properties. To model kinetics, we derive a master equation and solve it for several loading protocols. The developed formalism is applicable to a broad range of allosteric systems with mean-field interactions.

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

Wedding, Jason L.; Harris, Hugh H.; Bader, Christie A.

Optical fluorescence microscopy was used in conjunction with X-ray fluorescence microscopy to monitor the stability and intracellular distribution of the luminescent rhenium(I) complex fac-[Re(CO) 3(phen)L], where phen = 1,10-phenathroline and L = 5-(4-iodophenyl)tetrazolato, in 22Rv1 cells. The rhenium complex showed no signs of ancillary ligand dissociation, a conclusion based on data obtained via X-ray fluorescence imaging aligning iodine and rhenium distributions. A diffuse reticular localisation was detected for the complex, in the nuclear/perinuclear region of cells, by either optical or X-ray fluorescence techniques. Furthermore, X-ray fluorescence also showed that the Re-I complex disrupted the homeostasis of some biologically relevant elements,more » such as chlorine, potassium and zinc.« less

Biologics in pediatric psoriasis - efficacy and safety.

PubMed

Dogra, Sunil; Mahajan, Rahul

2018-01-01

Childhood psoriasis is a special situation that is a management challenge for the treating dermatologist. As is the situation with traditional systemic agents, which are commonly used in managing severe psoriasis in children, the biologics are being increasingly used in the recalcitrant disease despite limited data on long term safety. Areas covered: We performed an extensive literature search to collect evidence-based data on the use of biologics in pediatric psoriasis. The relevant literature published from 2000 to September 2017 was obtained from PubMed, using the MeSH words 'biologics', 'biologic response modifiers' and 'treatment of pediatric/childhood psoriasis'. All clinical trials, randomized double-blind or single-blind controlled trials, open-label studies, retrospective studies, reviews, case reports and letters concerning the use of biologics in pediatric psoriasis were screened. Articles covering the use of biologics in pediatric psoriasis were screened and reference lists in the selected articles were scrutinized to identify other relevant articles that had not been found in the initial search. Articles without relevant information about biologics in general (e.g. its mechanism of action, pharmacokinetics and adverse effects) and its use in psoriasis in particular were excluded. We screened 427 articles and finally selected 41 relevant articles. Expert opinion: The available literature on the use of biologics such as anti-tumor necrosis factor (TNF)-α agents, and anti-IL-12/23 agents like ustekinumab suggests that these are effective and safe in managing severe pediatric psoriasis although there is an urgent need to generate more safety data. Dermatologists must be careful about the potential adverse effects of the biologics before administering them to children with psoriasis. It is likely that with rapidly evolving scenario of biologics in psoriasis, these will prove to be very useful molecules particularly in managing severe and recalcitrant psoriasis in pediatric age group.

Quantification of 2D elemental distribution maps of intermediate-thick biological sections by low energy synchrotron μ-X-ray fluorescence spectrometry

NASA Astrophysics Data System (ADS)

Kump, P.; Vogel-Mikuš, K.

2018-05-01

Two fundamental-parameter (FP) based models for quantification of 2D elemental distribution maps of intermediate-thick biological samples by synchrotron low energy μ-X-ray fluorescence spectrometry (SR-μ-XRF) are presented and applied to the elemental analysis in experiments with monochromatic focused photon beam excitation at two low energy X-ray fluorescence beamlines—TwinMic, Elettra Sincrotrone Trieste, Italy, and ID21, ESRF, Grenoble, France. The models assume intermediate-thick biological samples composed of measured elements, the sources of the measurable spectral lines, and by the residual matrix, which affects the measured intensities through absorption. In the first model a fixed residual matrix of the sample is assumed, while in the second model the residual matrix is obtained by the iteration refinement of elemental concentrations and an adjusted residual matrix. The absorption of the incident focused beam in the biological sample at each scanned pixel position, determined from the output of a photodiode or a CCD camera, is applied as a control in the iteration procedure of quantification.

The mammary gland in domestic ruminants: a systems biology perspective.

PubMed

Ferreira, Ana M; Bislev, Stine L; Bendixen, Emøke; Almeida, André M

2013-12-06

Milk and dairy products are central elements in the human diet. It is estimated that 108kg of milk per year are consumed per person worldwide. Therefore, dairy production represents a relevant fraction of the economies of many countries, being cattle, sheep, goat, water buffalo, and other ruminants the main species used worldwide. An adequate management of dairy farming cannot be achieved without the knowledge on the biological mechanisms behind lactation in ruminants. Thus, understanding the morphology, development and regulation of the mammary gland in health, disease and production is crucial. Presently, innovative and high-throughput technologies such as genomics, transcriptomics, proteomics and metabolomics allow a much broader and detailed knowledge on such issues. Additionally, the application of a systems biology approach to animal science is vastly growing, as new advances in one field of specialization or animal species lead to new lines of research in other areas or/and are expanded to other species. This article addresses how modern research approaches may help us understand long-known issues in mammary development, lactation biology and dairy production. Dairy production depends upon the knowledge of the morphology and regulation of the mammary gland and lactation. High-throughput technologies allow a much broader and detailed knowledge on the biology of the mammary gland. This paper reviews the major contributions that genomics, transcriptomics, metabolomics and proteomics approaches have provided to understand the regulation of the mammary gland in health, disease and production. In the context of mammary gland "omics"-based research, the integration of results using a Systems Biology Approach is of key importance. © 2013.

Trace Elements in Ovaries: Measurement and Physiology.

PubMed

Ceko, Melanie J; O'Leary, Sean; Harris, Hugh H; Hummitzsch, Katja; Rodgers, Raymond J

2016-04-01

Traditionally, research in the field of trace element biology and human and animal health has largely depended on epidemiological methods to demonstrate involvement in biological processes. These studies were typically followed by trace element supplementation trials or attempts at identification of the biochemical pathways involved. With the discovery of biological molecules that contain the trace elements, such as matrix metalloproteinases containing zinc (Zn), cytochrome P450 enzymes containing iron (Fe), and selenoproteins containing selenium (Se), much of the current research focuses on these molecules, and, hence, only indirectly on trace elements themselves. This review focuses largely on two synchrotron-based x-ray techniques: X-ray absorption spectroscopy and x-ray fluorescence imaging that can be used to identify the in situ speciation and distribution of trace elements in tissues, using our recent studies of bovine ovaries, where the distribution of Fe, Se, Zn, and bromine were determined. It also discusses the value of other techniques, such as inductively coupled plasma mass spectrometry, used to garner information about the concentrations and elemental state of the trace elements. These applications to measure trace elemental distributions in bovine ovaries at high resolutions provide new insights into possible roles for trace elements in the ovary. © 2016 by the Society for the Study of Reproduction, Inc.

Imaging and elemental mapping of biological specimens with a dual-EDS dedicated scanning transmission electron microscope.

PubMed

Wu, J S; Kim, A M; Bleher, R; Myers, B D; Marvin, R G; Inada, H; Nakamura, K; Zhang, X F; Roth, E; Li, S Y; Woodruff, T K; O'Halloran, T V; Dravid, Vinayak P

2013-05-01

A dedicated analytical scanning transmission electron microscope (STEM) with dual energy dispersive spectroscopy (EDS) detectors has been designed for complementary high performance imaging as well as high sensitivity elemental analysis and mapping of biological structures. The performance of this new design, based on a Hitachi HD-2300A model, was evaluated using a variety of biological specimens. With three imaging detectors, both the surface and internal structure of cells can be examined simultaneously. The whole-cell elemental mapping, especially of heavier metal species that have low cross-section for electron energy loss spectroscopy (EELS), can be faithfully obtained. Optimization of STEM imaging conditions is applied to thick sections as well as thin sections of biological cells under low-dose conditions at room and cryogenic temperatures. Such multimodal capabilities applied to soft/biological structures usher a new era for analytical studies in biological systems. Copyright © 2013 Elsevier B.V. All rights reserved.

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

EPA Science Inventory

The Ecological Risk Assessment Support Center (ERASC) announced the release of the final report, Determination of the Biologically Relevant Sampling Depth for Terrestrial and Aquatic Ecological Risk Assessments. This technical paper provides defensible approximations fo...

The importance of trace element speciation in biomedical science.

PubMed

Templeton, Douglas M

2003-04-01

According to IUPAC terminology, trace element speciation reflects differences in chemical composition at multiple levels from nuclear and electronic structure to macromolecular complexation. In the medical sciences, all levels of composition are important in various circumstances, and each can affect the bioavailability, distribution, physiological function, toxicity, diagnostic utility, and therapeutic potential of an element. Here we discuss, with specific examples, three biological principles in the intimate relation between speciation and biological behavior: i) the kinetics of interconversion of species determines distribution within the organism, ii) speciation governs transport across various biological barriers, and iii) speciation can limit potentially undesirable interactions between physiologically essential elements. We will also describe differences in the speciation of iron in states of iron overload, to illustrate how speciation analysis can provide insight into cellular processes in human disease.

Tuning the properties of conjugated polyelectrolytes and application in a biosensor platform

DOEpatents

Chen, Liaohai

2004-05-18

The present invention provides a method of detecting a biological agent including contacting a sample with a sensor including a polymer system capable of having an alterable measurable property from the group of luminescence, anisotropy, redox potential and uv/vis absorption, the polymer system including an ionic conjugated polymer and an electronically inert polyelectrolyte having a biological agent recognition element bound thereto, the electronically inert polyelectrolyte adapted for undergoing a conformational structural change upon exposure to a biological agent having affinity for binding to the recognition element bound to the electronically inert polyelectrolyte, and, detecting the detectable change in the alterable measurable property. A chemical moiety being the reaction product of (i) a polyelectrolyte monomer and (ii) a biological agent recognition element-substituted polyelectrolyte monomer is also provided.

All y'all need to know 'bout retroelements in cancer.

PubMed

Belancio, Victoria P; Roy-Engel, Astrid M; Deininger, Prescott L

2010-08-01

Genetic instability is one of the principal hallmarks and causative factors in cancer. Human transposable elements (TE) have been reported to cause human diseases, including several types of cancer through insertional mutagenesis of genes critical for preventing or driving malignant transformation. In addition to retrotransposition-associated mutagenesis, TEs have been found to contribute even more genomic rearrangements through non-allelic homologous recombination. TEs also have the potential to generate a wide range of mutations derivation of which is difficult to directly trace to mobile elements, including double strand breaks that may trigger mutagenic genomic rearrangements. Genome-wide hypomethylation of TE promoters and significantly elevated TE expression in almost all human cancers often accompanied by the loss of critical DNA sensing and repair pathways suggests that the negative impact of mobile elements on genome stability should increase as human tumors evolve. The biological consequences of elevated retroelement expression, such as the rate of their amplification, in human cancers remain obscure, particularly, how this increase translates into disease-relevant mutations. This review is focused on the cellular mechanisms that control human TE-associated mutagenesis in cancer and summarizes the current understanding of TE contribution to genetic instability in human malignancies. Copyright © 2010 Elsevier Ltd. All rights reserved.

Elemental mapping of biological samples using a scanning proton microprobe

NASA Astrophysics Data System (ADS)

Watt, F.; Grime, G. W.

1988-03-01

Elemental mapping using a scanning proton microprobe (SPM) can be a powerful technique for probing trace elements in biology, allowing complex interfaces to be studied in detail, identifying contamination and artefacts present in the specimen, and in certain circumstances obtaining indirect chemical information. Examples used to illustrate the advantages of the technique include the elemental mapping of growing pollen tubes, honey bee brain section, a mouse macrophage cell, human liver section exhibiting primary biliary cirrhosis, and the attack by a mildew fungus on a pea leaf.

Fish gelatin thin film standards for biological application of PIXE

NASA Astrophysics Data System (ADS)

Manuel, Jack E.; Rout, Bibhudutta; Szilasi, Szabolcs Z.; Bohara, Gyanendra; Deaton, James; Luyombya, Henry; Briski, Karen P.; Glass, Gary A.

2014-08-01

There exists a critical need to understand the flow and accumulation of metallic ions, both naturally occurring and those introduced to biological systems. In this paper the results of fabricating thin film elemental biological standards containing nearly any combination of trace elements in a protein matrix are presented. Because it is capable of high elemental sensitivity, particle induced X-ray emission spectrometry (PIXE) is an excellent candidate for in situ analysis of biological tissues. Additionally, the utilization of microbeam PIXE allows the determination of elemental concentrations in and around biological cells. However, obtaining elemental reference standards with the same matrix constituents as brain tissue is difficult. An excellent choice for simulating brain-like tissue is Norland® photoengraving glue which is derived from fish skin. Fish glue is water soluble, liquid at room temperature, and resistant to dilute acid. It can also be formed into a thin membrane which dries into a durable, self-supporting film. Elements of interest are introduced to the fish glue in precise volumetric additions of well quantified atomic absorption standard solutions. In this study GeoPIXE analysis package is used to quantify elements intrinsic to the fish glue as well as trace amounts of manganese added to the sample. Elastic (non-Rutherford) backscattered spectroscopy (EBS) and the 1.734 MeV proton-on-carbon 12C(p,p)12C resonance is used for a normalization scheme of the PIXE spectra to account for any discrepancies in X-ray production arising from thickness variation of the prepared standards. It is demonstrated that greater additions of the atomic absorption standard cause a viscosity reduction of the liquid fish glue resulting in thinner films but the film thickness can be monitored by using simultaneous PIXE and EBS proton data acquisition.

Nanotribology of charged polymer brushes

NASA Astrophysics Data System (ADS)

Klein, Jacob

Polymers at surfaces, whose modern understanding may be traced back to early work by Sam Edwards1, have become a paradigm for modification of surface properties, both as steric stabilizers and as remarkable boundary lubricants2. Charged polymer brushes are of particular interest, with both technological implications and especially biological relevance where most macromolecules are charged. In the context of biolubrication, relevant in areas from dry eye syndrome to osteoarthritis, charged polymer surface phases and their complexes with other macromolecules may play a central role. The hydration lubrication paradigm, where tenaciously-held yet fluid hydration shells surrounding ions or zwitterions serve as highly-efficient friction-reducing elements, has been invoked to understand the excellent lubrication provided both by ionized3 and by zwitterionic4 brushes. In this talk we describe recent advances in our understanding of the nanotribology of such charged brush systems. We consider interactions between charged end-grafted polymers, and how one may disentangle the steric from the electrostatic surface forces5. We examine the limits of lubrication by ionized brushes, both synthetic and of biological origins, and how highly-hydrated zwitterionic chains may provide extremely effective boundary lubrication6. Finally we describe how the lubrication of articular cartilage in the major joints, a tribosystem presenting some of the greatest challenges and opportunities, may be understood in terms of a supramolecular synergy between charged surface-attached polymers and zwitterionic groups7. Work supported by European Research Council (HydrationLube), Israel Science Foundation (ISF), Petroleum Research Fund of the American Chemical Society, ISF-NSF China Joint Program.

Assessment of health status of oysters (Crassostreagigas) exposed to environmentally relevant concentrations of Ag and Cu in brackish waters

NASA Astrophysics Data System (ADS)

Rementeria, Ane; Mikolaczyk, Mathilde; Peña, Ainhize; Lanceleur, Laurent; Blanc, Gérard; Soto, Manu; Schäfer, Jörg; Zaldibar, Beñat

2017-12-01

Human activities have altered estuarine environments leading to increased presence of different pollutants including metals. Although the implementation of new environmental policies has caused a considerable decrease in trace metal concentrations in estuaries around the Bay of Biscay, some elements such as copper (Cu) and silver (Ag) are still present in relatively high concentrations. Oysters have been widely used in environmental biomonitoring programs as sentinel organisms. Oysters Crassostrea gigas from an uncontaminated estuary were exposed to sublethal, environmentally relevant concentrations of Cu (2000 ng Cu/L) and Ag (500 ng Ag/L) during 14 days in brackish water (S = 18). A battery of cell and tissue level (exposure) biomarkers at different levels of biological complexity was applied and integrated into the Integrative Biological Response (IBR) index including: metallothionein contents, intralysosomal metal accumulation, digestive gland atrophy and digestive gland tissue integrity. Condition Index (CI) was incorporated into the IBR index as a complementary parameter that reflects the general physiological condition of oysters (organism level). Results indicated an increase in intralysosomal metal accumulation after 7 and 14 days of exposure to Ag together with an increase in the digestive epithelium atrophy and lipofuscin content after 7 days of exposure to Ag. The responses detected with the aid of biomarkers integrated in the IBR index showed higher toxicity in oysters exposed to Ag, inducing the clear onset of detoxification processes which also occurred, to a lower extent, in Cu-exposed oysters.

Behavioral and Biological Effects of Housing Conditions and Stress in Male Rats - Relevance to Heart Disease

DTIC Science & Technology

2006-08-01

animals had higher corticosterone than Combined Enrichment/Not Stressed (CNS) animals (F [1, 22 ] = 6.78, p < 0.01). The greatest effects were in...biological effects of stress. In particular, plasma corticosterone levels have been reported to increase in response to stressors in different... effects of restraint stress on the biological and behavioral factors relevant to cardiovascular disease (e.g., plasma corticosterone levels

Religion and morality.

PubMed

McKay, Ryan; Whitehouse, Harvey

2015-03-01

The relationship between religion and morality has long been hotly debated. Does religion make us more moral? Is it necessary for morality? Do moral inclinations emerge independently of religious intuitions? These debates, which nowadays rumble on in scientific journals as well as in public life, have frequently been marred by a series of conceptual confusions and limitations. Many scientific investigations have failed to decompose "religion" and "morality" into theoretically grounded elements; have adopted parochial conceptions of key concepts-in particular, sanitized conceptions of "prosocial" behavior; and have neglected to consider the complex interplay between cognition and culture. We argue that to make progress, the categories "religion" and "morality" must be fractionated into a set of biologically and psychologically cogent traits, revealing the cognitive foundations that shape and constrain relevant cultural variants. We adopt this fractionating strategy, setting out an encompassing evolutionary framework within which to situate and evaluate relevant evidence. Our goals are twofold: to produce a detailed picture of the current state of the field, and to provide a road map for future research on the relationship between religion and morality. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Signal Propagation in Proteins and Relation to Equilibrium Fluctuations

PubMed Central

Chennubhotla, Chakra; Bahar, Ivet

2007-01-01

Elastic network (EN) models have been widely used in recent years for describing protein dynamics, based on the premise that the motions naturally accessible to native structures are relevant to biological function. We posit that equilibrium motions also determine communication mechanisms inherent to the network architecture. To this end, we explore the stochastics of a discrete-time, discrete-state Markov process of information transfer across the network of residues. We measure the communication abilities of residue pairs in terms of hit and commute times, i.e., the number of steps it takes on an average to send and receive signals. Functionally active residues are found to possess enhanced communication propensities, evidenced by their short hit times. Furthermore, secondary structural elements emerge as efficient mediators of communication. The present findings provide us with insights on the topological basis of communication in proteins and design principles for efficient signal transduction. While hit/commute times are information-theoretic concepts, a central contribution of this work is to rigorously show that they have physical origins directly relevant to the equilibrium fluctuations of residues predicted by EN models. PMID:17892319

Religion and Morality

PubMed Central

2014-01-01

The relationship between religion and morality has long been hotly debated. Does religion make us more moral? Is it necessary for morality? Do moral inclinations emerge independently of religious intuitions? These debates, which nowadays rumble on in scientific journals as well as in public life, have frequently been marred by a series of conceptual confusions and limitations. Many scientific investigations have failed to decompose “religion” and “morality” into theoretically grounded elements; have adopted parochial conceptions of key concepts—in particular, sanitized conceptions of “prosocial” behavior; and have neglected to consider the complex interplay between cognition and culture. We argue that to make progress, the categories “religion” and “morality” must be fractionated into a set of biologically and psychologically cogent traits, revealing the cognitive foundations that shape and constrain relevant cultural variants. We adopt this fractionating strategy, setting out an encompassing evolutionary framework within which to situate and evaluate relevant evidence. Our goals are twofold: to produce a detailed picture of the current state of the field, and to provide a road map for future research on the relationship between religion and morality. PMID:25528346

The biology and evolution of transposable elements in parasites.

PubMed

Thomas, M Carmen; Macias, Francisco; Alonso, Carlos; López, Manuel C

2010-07-01

Transposable elements (TEs) are dynamic elements that can reshape host genomes by generating rearrangements with the potential to create or disrupt genes, to shuffle existing genes, and to modulate their patterns of expression. In the genomes of parasites that infect mammals several TEs have been identified that probably have been maintained throughout evolution due to their contribution to gene function and regulation of gene expression. This review addresses how TEs are organized, how they colonize the genomes of mammalian parasites, the functional role these elements play in parasite biology, and the interactions between these elements and the parasite genome. Copyright 2010 Elsevier Ltd. All rights reserved.

Developing core elements and checklist items for global hospital antimicrobial stewardship programmes: a consensus approach.

PubMed

Pulcini, C; Binda, F; Lamkang, A S; Trett, A; Charani, E; Goff, D A; Harbarth, S; Hinrichsen, S L; Levy-Hara, G; Mendelson, M; Nathwani, D; Gunturu, R; Singh, S; Srinivasan, A; Thamlikitkul, V; Thursky, K; Vlieghe, E; Wertheim, H; Zeng, M; Gandra, S; Laxminarayan, R

2018-04-03

With increasing global interest in hospital antimicrobial stewardship (AMS) programmes, there is a strong demand for core elements of AMS to be clearly defined on the basis of principles of effectiveness and affordability. To date, efforts to identify such core elements have been limited to Europe, Australia, and North America. The aim of this study was to develop a set of core elements and their related checklist items for AMS programmes that should be present in all hospitals worldwide, regardless of resource availability. A literature review was performed by searching Medline and relevant websites to retrieve a list of core elements and items that could have global relevance. These core elements and items were evaluated by an international group of AMS experts using a structured modified Delphi consensus procedure, using two-phased online in-depth questionnaires. The literature review identified seven core elements and their related 29 checklist items from 48 references. Fifteen experts from 13 countries in six continents participated in the consensus procedure. Ultimately, all seven core elements were retained, as well as 28 of the initial checklist items plus one that was newly suggested, all with ≥80% agreement; 20 elements and items were rephrased. This consensus on core elements for hospital AMS programmes is relevant to both high- and low-to-middle-income countries and could facilitate the development of national AMS stewardship guidelines and adoption by healthcare settings worldwide. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.

Bioavailability of antioxidants in extruded products prepared from purple potato and dry pea flours

USDA-ARS?s Scientific Manuscript database

Measuring antioxidant activity using biological relevant assay is unique to understand the role of phytochemicals in vivo than common chemical assays. Cellular antioxidant activity assay could provide more biological relevant information on bioactive compounds in the raw as well as processed food pr...

Brachypodium as a model for the grasses: today and the future

USDA-ARS?s Scientific Manuscript database

Over the past several years, Brachypodium distachyon (Brachypodium) has emerged as a tractable model system to study biological questions relevant to the grasses. To place its relevance in the larger context of plant biology, we outline here the expanding adoption of Brachypodium as a model grass an...

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...

Remote monitoring of vibrational information in spider webs.

PubMed

Mortimer, B; Soler, A; Siviour, C R; Vollrath, F

2018-05-22

Spiders are fascinating model species to study information-acquisition strategies, with the web acting as an extension of the animal's body. Here, we compare the strategies of two orb-weaving spiders that acquire information through vibrations transmitted and filtered in the web. Whereas Araneus diadematus monitors web vibration directly on the web, Zygiella x-notata uses a signal thread to remotely monitor web vibration from a retreat, which gives added protection. We assess the implications of these two information-acquisition strategies on the quality of vibration information transfer, using laser Doppler vibrometry to measure vibrations of real webs and finite element analysis in computer models of webs. We observed that the signal thread imposed no biologically relevant time penalty for vibration propagation. However, loss of energy (attenuation) was a cost associated with remote monitoring via a signal thread. The findings have implications for the biological use of vibrations by spiders, including the mechanisms to locate and discriminate between vibration sources. We show that orb-weaver spiders are fascinating examples of organisms that modify their physical environment to shape their information-acquisition strategy.

Remote monitoring of vibrational information in spider webs

NASA Astrophysics Data System (ADS)

Mortimer, B.; Soler, A.; Siviour, C. R.; Vollrath, F.

2018-06-01

Spiders are fascinating model species to study information-acquisition strategies, with the web acting as an extension of the animal's body. Here, we compare the strategies of two orb-weaving spiders that acquire information through vibrations transmitted and filtered in the web. Whereas Araneus diadematus monitors web vibration directly on the web, Zygiella x-notata uses a signal thread to remotely monitor web vibration from a retreat, which gives added protection. We assess the implications of these two information-acquisition strategies on the quality of vibration information transfer, using laser Doppler vibrometry to measure vibrations of real webs and finite element analysis in computer models of webs. We observed that the signal thread imposed no biologically relevant time penalty for vibration propagation. However, loss of energy (attenuation) was a cost associated with remote monitoring via a signal thread. The findings have implications for the biological use of vibrations by spiders, including the mechanisms to locate and discriminate between vibration sources. We show that orb-weaver spiders are fascinating examples of organisms that modify their physical environment to shape their information-acquisition strategy.

Long-range electron tunneling.

PubMed

Winkler, Jay R; Gray, Harry B

2014-02-26

Electrons have so little mass that in less than a second they can tunnel through potential energy barriers that are several electron-volts high and several nanometers wide. Electron tunneling is a critical functional element in a broad spectrum of applications, ranging from semiconductor diodes to the photosynthetic and respiratory charge transport chains. Prior to the 1970s, chemists generally believed that reactants had to collide in order to effect a transformation. Experimental demonstrations that electrons can transfer between reactants separated by several nanometers led to a revision of the chemical reaction paradigm. Experimental investigations of electron exchange between redox partners separated by molecular bridges have elucidated many fundamental properties of these reactions, particularly the variation of rate constants with distance. Theoretical work has provided critical insights into the superexchange mechanism of electronic coupling between distant redox centers. Kinetics measurements have shown that electrons can tunnel about 2.5 nm through proteins on biologically relevant time scales. Longer-distance biological charge flow requires multiple electron tunneling steps through chains of redox cofactors. The range of phenomena that depends on long-range electron tunneling continues to expand, providing new challenges for both theory and experiment.

In vitro element release and biological aspects of base–metal alloys for metal-ceramic applications

PubMed Central

Holm, Charlotta; Morisbak, Else; Kalfoss, Torill; Dahl, Jon E.

2015-01-01

Abstract Objective: The aims of this study were to investigate the release of element from, and the biological response in vitro to, cobalt–chromium alloys and other base–metal alloys used for the fabrication of metal-ceramic restorations. Material and methods: Eighteen different alloys were investigated. Nine cobalt–chromium alloys, three nickel–chromium alloys, two cobalt–chromium–iron alloys, one palladium–silver alloy, one high-noble gold alloy, titanium grade II and one type III copper–aluminium alloy. Pure copper served as positive control. The specimens were prepared according to the ISO standards for biological and corrosion testing. Passive leaching of elements was measured by using Inductively Coupled Plasma – Mass Spectrometry (ICP-MS) after incubation in cell culture media, MEM, for 3 days. Corrosion testing was carried out in 0.9% sodium chloride (NaCl) and 1% lactic acid for 7 days, and the element release was measured by Inductively Coupled Plasma – Optical Emission Spectroscopy (ICP-OES). The biological response from the extract solutions was measured though MTT cytotoxicity testing and the Hen's egg test-chorio-allantoic membrane (HET-CAM) technique for irritationt. Results: The corrosion test showed similar element release from base-metal alloys compared to noble alloys such as gold. Apart from the high-copper alloy, all alloys expressed low element release in the immersion test, no cytotoxic effect in the MTT test, and were rated non-irritant in the HET-CAM test. Conclusions: Minimal biological response was observed for all the alloys tested, with the exception of the high-copper alloy. PMID:28642904

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

PubMed

Sakaki, Michiko; Niki, Kazuhisa; Mather, Mara

2012-03-01

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 (1) biologically emotional images hold attention more strongly than do socially emotional images, (2) memory for biologically emotional images was enhanced even with limited cognitive resources, but (3) 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 the visual cortex and greater functional connectivity between the 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 the medial prefrontal cortex (MPFC) and yielded stronger functional connectivity between the amygdala and MPFC than did biological images. Thus, it appears that emotional processing of social stimuli involves elaborative processing requiring frontal lobe activity.

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

A glimpse on biological activities of tellurium compounds.

PubMed

Cunha, Rodrigo L O R; Gouvea, Iuri E; Juliano, Luiz

2009-09-01

Tellurium is a rare element which has been regarded as a toxic, non-essential trace element and its biological role is not clearly established to date. Besides of that, the biological effects of elemental tellurium and some of its inorganic and organic derivatives have been studied, leading to a set of interesting and promising applications. As an example, it can be highlighted the uses of alkali-metal tellurites and tellurates in microbiology, the antioxidant effects of organotellurides and diorganoditellurides and the immunomodulatory effects of the non-toxic inorganic tellurane, named AS-101, and the plethora of its uses. Inasmuch, the nascent applications of organic telluranes (organotelluranes) as protease inhibitors and its applications in disease models are the most recent contribution to the scenario of the biological effects and applications of tellurium and its compounds discussed in this manuscript.

Evolutionary perspectives on learning: conceptual and methodological issues in the study of adaptive specializations.

PubMed

Krause, Mark A

2015-07-01

Inquiry into evolutionary adaptations has flourished since the modern synthesis of evolutionary biology. Comparative methods, genetic techniques, and various experimental and modeling approaches are used to test adaptive hypotheses. In psychology, the concept of adaptation is broadly applied and is central to comparative psychology and cognition. The concept of an adaptive specialization of learning is a proposed account for exceptions to general learning processes, as seen in studies of Pavlovian conditioning of taste aversions, sexual responses, and fear. The evidence generally consists of selective associations forming between biologically relevant conditioned and unconditioned stimuli, with conditioned responses differing in magnitude, persistence, or other measures relative to non-biologically relevant stimuli. Selective associations for biologically relevant stimuli may suggest adaptive specializations of learning, but do not necessarily confirm adaptive hypotheses as conceived of in evolutionary biology. Exceptions to general learning processes do not necessarily default to an adaptive specialization explanation, even if experimental results "make biological sense". This paper examines the degree to which hypotheses of adaptive specializations of learning in sexual and fear response systems have been tested using methodologies developed in evolutionary biology (e.g., comparative methods, quantitative and molecular genetics, survival experiments). A broader aim is to offer perspectives from evolutionary biology for testing adaptive hypotheses in psychological science.

Advancing Translational Space Research Through Biospecimen Sharing: Amplified Impact of Studies Utilizing Analogue Space Platforms

NASA Technical Reports Server (NTRS)

Staten, B.; Moyer, E.; Vizir, V.; Gompf, H.; Hoban-Higgins, T.; Lewis, L.; Ronca, A.; Fuller, C. A.

2016-01-01

Biospecimen Sharing Programs (BSPs) have been organized by NASA Ames Research Center since the 1960s with the goal of maximizing utilization and scientific return from rare, complex and costly spaceflight experiments. BSPs involve acquiring otherwise unused biological specimens from primary space research experiments for distribution to secondary experiments. Here we describe a collaboration leveraging Ames expertise in biospecimen sharing to magnify the scientific impact of research informing astronaut health funded by the NASA Human Research Program (HRP) Human Health Countermeasures (HHC) Element. The concept expands biospecimen sharing to one-off ground-based studies utilizing analogue space platforms (e.g., Hindlimb Unloading (HLU), Artificial Gravity) for rodent experiments, thereby significantly broadening the range of research opportunities with translational relevance for protecting human health in space and on Earth.

Model systems: how chemical biologists study RNA

PubMed Central

Rios, Andro C.; Tor, Yitzhak

2009-01-01

Ribonucleic acids are structurally and functionally sophisticated biomolecules and the use of models, frequently truncated or modified sequences representing functional domains of the natural systems, is essential to their exploration. Functional non-coding RNAs such as miRNAs, riboswitches, and, in particular, ribozymes, have changed the view of RNA’s role in biology and its catalytic potential. The well-known truncated hammerhead model has recently been refined and new data provide a clearer molecular picture of the elements responsible for its catalytic power. A model for the spliceosome, a massive and highly intricate ribonucleoprotein, is also emerging, although its true utility is yet to be cemented. Such catalytic model systems could also serve as “chemo-paleontological” tools, further refining the RNA world hypothesis and its relevance to the origin and evolution of life. PMID:19879179

Seos - EARSEL'S Project on Science Education Through Earth Observation for High Schools

NASA Astrophysics Data System (ADS)

Reuter, R.

2011-09-01

SEOS is an initiative for using remote sensing in science education curricula in high schools funded under the 6th Framework Programme of the European Commission (EC). Eleven partners from several European countries, in cooperation with the European Space Agency (ESA) and teachers from European high schools, created e-learning tutorials for science students in high schools. The tutorials cover many disciplines such as physics, biology, geography, mathematics and engineering, emphasising the interdisciplinary character of remote sensing. They are the core element of the SEOS Learning Management System, allowing teachers to create their own courses, to distribute already available or new worksheets to the students for homework and to collect the results. Forums are available for teachers, students and other users to exchange information and discuss topics relevant for their study.

Overview of Micro- and Nano-Technology Tools for Stem Cell Applications: Micropatterned and Microelectronic Devices

PubMed Central

Cagnin, Stefano; Cimetta, Elisa; Guiducci, Carlotta; Martini, Paolo; Lanfranchi, Gerolamo

2012-01-01

In the past few decades the scientific community has been recognizing the paramount role of the cell microenvironment in determining cell behavior. In parallel, the study of human stem cells for their potential therapeutic applications has been progressing constantly. The use of advanced technologies, enabling one to mimic the in vivo stem cell microenviroment and to study stem cell physiology and physio-pathology, in settings that better predict human cell biology, is becoming the object of much research effort. In this review we will detail the most relevant and recent advances in the field of biosensors and micro- and nano-technologies in general, highlighting advantages and disadvantages. Particular attention will be devoted to those applications employing stem cells as a sensing element. PMID:23202240

Overview of micro- and nano-technology tools for stem cell applications: micropatterned and microelectronic devices.

PubMed

Cagnin, Stefano; Cimetta, Elisa; Guiducci, Carlotta; Martini, Paolo; Lanfranchi, Gerolamo

2012-11-19

In the past few decades the scientific community has been recognizing the paramount role of the cell microenvironment in determining cell behavior. In parallel, the study of human stem cells for their potential therapeutic applications has been progressing constantly. The use of advanced technologies, enabling one to mimic the in vivo stem cell microenviroment and to study stem cell physiology and physio-pathology, in settings that better predict human cell biology, is becoming the object of much research effort. In this review we will detail the most relevant and recent advances in the field of biosensors and micro- and nano-technologies in general, highlighting advantages and disadvantages. Particular attention will be devoted to those applications employing stem cells as a sensing element.

Metal-containing and related polymers for biomedical applications.

PubMed

Yan, Yi; Zhang, Jiuyang; Ren, Lixia; Tang, Chuanbing

2016-10-07

A survey of the most recent progress in the biomedical applications of metal-containing polymers is given. Due to the unique optical, electrochemical, and magnetic properties, at least 30 different metal elements, most of them transition metals, are introduced into polymeric frameworks for interactions with biology-relevant substrates via various means. Inspired by the advance of metal-containing small molecular drugs and promoted by the great progress in polymer chemistry, metal-containing polymers have gained momentum during recent decades. According to their different applications, this review summarizes the following biomedical applications: (1) metal-containing polymers as drug delivery vehicles; (2) metal-containing polymeric drugs and biocides, including antimicrobial and antiviral agents, anticancer drugs, photodynamic therapy agents, radiotherapy agents and biocides; (3) metal-containing polymers as biosensors, and (4) metal-containing polymers in bioimaging.

Intracellular distribution and stability of a luminescent rhenium(i) tricarbonyl tetrazolato complex using epifluorescence microscopy in conjunction with X-ray fluorescence imaging.

PubMed

Wedding, J L; Harris, H H; Bader, C A; Plush, S E; Mak, R; Massi, M; Brooks, D A; Lai, B; Vogt, S; Werrett, M V; Simpson, P V; Skelton, B W; Stagni, S

2017-04-19

Optical epifluorescence microscopy was used in conjunction with X-ray fluorescence imaging to monitor the stability and intracellular distribution of the luminescent rhenium(i) complex fac-[Re(CO) 3 (phen)L], where phen = 1,10-phenathroline and L = 5-(4-iodophenyl)tetrazolato, in 22Rv1 cells. The rhenium complex showed no signs of ancillary ligand dissociation, a conclusion based on data obtained via X-ray fluorescence imaging aligning iodine and rhenium distributions. A diffuse reticular localisation was detected for the complex in the nuclear/perinuclear region of cells, by either optical or X-ray fluorescence imaging techniques. X-ray fluorescence also showed that the rhenium complex disrupted the homeostasis of some biologically relevant elements, such as chlorine, potassium and zinc.

Validation of an entirely in vitro approach for rapid prototyping of DNA regulatory elements for synthetic biology

PubMed Central

Chappell, James; Jensen, Kirsten; Freemont, Paul S.

2013-01-01

A bottleneck in our capacity to rationally and predictably engineer biological systems is the limited number of well-characterized genetic elements from which to build. Current characterization methods are tied to measurements in living systems, the transformation and culturing of which are inherently time-consuming. To address this, we have validated a completely in vitro approach for the characterization of DNA regulatory elements using Escherichia coli extract cell-free systems. Importantly, we demonstrate that characterization in cell-free systems correlates and is reflective of performance in vivo for the most frequently used DNA regulatory elements. Moreover, we devise a rapid and completely in vitro method to generate DNA templates for cell-free systems, bypassing the need for DNA template generation and amplification from living cells. This in vitro approach is significantly quicker than current characterization methods and is amenable to high-throughput techniques, providing a valuable tool for rapidly prototyping libraries of DNA regulatory elements for synthetic biology. PMID:23371936

Biological trade and markets

PubMed Central

2016-01-01

Cooperation between organisms can often be understood, like trade between merchants, as a mutually beneficial exchange of services, resources or other ‘commodities’. Mutual benefits alone, however, are not sufficient to explain the evolution of trade-based cooperation. First, organisms may reject a particular trade if another partner offers a better deal. Second, while human trade often entails binding contracts, non-human trade requires unwritten ‘terms of contract’ that ‘self-stabilize’ trade and prevent cheating even if all traders strive to maximize fitness. Whenever trading partners can be chosen, market-like situations arise in nature that biologists studying cooperation need to account for. The mere possibility of exerting partner choice stabilizes many forms of otherwise cheatable trade, induces competition, facilitates the evolution of specialization and often leads to intricate forms of cooperation. We discuss selected examples to illustrate these general points and review basic conceptual approaches that are important in the theory of biological trade and markets. Comparing these approaches with theory in economics, it turns out that conventional models—often called ‘Walrasian’ markets—are of limited relevance to biology. In contrast, early approaches to trade and markets, as found in the works of Ricardo and Cournot, contain elements of thought that have inspired useful models in biology. For example, the concept of comparative advantage has biological applications in trade, signalling and ecological competition. We also see convergence between post-Walrasian economics and biological markets. For example, both economists and biologists are studying ‘principal–agent’ problems with principals offering jobs to agents without being sure that the agents will do a proper job. Finally, we show that mating markets have many peculiarities not shared with conventional economic markets. Ideas from economics are useful for biologists studying cooperation but need to be taken with caution. PMID:26729940

The Chemical Biology of S-Nitrosothiols

PubMed Central

Broniowska, Katarzyna A.

2012-01-01

Abstract Significance: S-nitrosothiol formation and protein S-nitrosation is an important nitric oxide (NO)-dependent signaling paradigm that is relevant to almost all aspects of cell biology, from proliferation, to homeostasis, to programmed cell death. However, the mechanisms by which S-nitrosothiols are formed are still largely unknown, and there are gaps of understanding between the known chemical biology of S-nitrosothiols and their reported functions. Recent Advances: This review attempts to describe the biological chemistry of S-nitrosation and to point out where the challenges lie in matching the known chemical biology of these compounds with their reported functions. The review will detail new discoveries concerning the mechanisms of the formation of S-nitrosothiols in biological systems. Critical Issues: Although S-nitrosothiols may be formed with some degree of specificity on particular protein thiols, through un-catalyzed chemistry, and mechanisms for their degradation and redistribution are present, these processes are not sufficient to explain the vast array of specific and targeted responses of NO that have been attributed to S-nitrosation. Elements of catalysis have been discovered in the formation, distribution, and metabolism of S-nitrosothiols, but it is less clear whether these represent a specific network for targeted NO-dependent signaling. Future Directions: Much recent work has uncovered new targets for S-nitrosation through either targeted or proteome-wide approaches There is a need to understand which of these modifications represent concerted and targeted signaling processes and which is an inevitable consequence of living with NO. There is still much to be learned about how NO transduces signals in cells and the role played by protein S-nitrosation. Antioxid. Redox Signal. 17, 969–980. PMID:22468855

Biological trade and markets.

PubMed

Hammerstein, Peter; Noë, Ronald

2016-02-05

Cooperation between organisms can often be understood, like trade between merchants, as a mutually beneficial exchange of services, resources or other 'commodities'. Mutual benefits alone, however, are not sufficient to explain the evolution of trade-based cooperation. First, organisms may reject a particular trade if another partner offers a better deal. Second, while human trade often entails binding contracts, non-human trade requires unwritten 'terms of contract' that 'self-stabilize' trade and prevent cheating even if all traders strive to maximize fitness. Whenever trading partners can be chosen, market-like situations arise in nature that biologists studying cooperation need to account for. The mere possibility of exerting partner choice stabilizes many forms of otherwise cheatable trade, induces competition, facilitates the evolution of specialization and often leads to intricate forms of cooperation. We discuss selected examples to illustrate these general points and review basic conceptual approaches that are important in the theory of biological trade and markets. Comparing these approaches with theory in economics, it turns out that conventional models-often called 'Walrasian' markets-are of limited relevance to biology. In contrast, early approaches to trade and markets, as found in the works of Ricardo and Cournot, contain elements of thought that have inspired useful models in biology. For example, the concept of comparative advantage has biological applications in trade, signalling and ecological competition. We also see convergence between post-Walrasian economics and biological markets. For example, both economists and biologists are studying 'principal-agent' problems with principals offering jobs to agents without being sure that the agents will do a proper job. Finally, we show that mating markets have many peculiarities not shared with conventional economic markets. Ideas from economics are useful for biologists studying cooperation but need to be taken with caution. © 2016 The Authors.

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...

Nuclear microscopy in trace-element biology — from cellular studies to the clinic

NASA Astrophysics Data System (ADS)

Lindh, Ulf

1993-05-01

The concentration and distribution of trace and major elements in cells are of great interest in cell biology. PIXE can provide elemental concentrations in the bulk of cells or organelles as other bulk techniques such as atomic absorption spectrophotometry and nuclear activation analysis. Supplementary information, perhaps more exciting, on the intracellular distributions of trace elements can be provided using nuclear microscopy. Intracellular distributions of trace elements in normal and malignant cells are presented. The toxicity of mercury and cadmium can be prevented by supplementation of the essential trace element selenium. Some results from an experimental animal model are discussed. The intercellular distribution of major and trace elements in isolated blood cells, as revealed by nuclear microscopy, provides useful clinical information. Examples are given concerning inflammatory connective-tissue diseases and the chronic fatigue syndrome.

Spectroscopy of Isolated Prebiotic Nucleobases

NASA Technical Reports Server (NTRS)

Svadlenak, Nathan; Callahan, Michael P.; Ligare, Marshall; Gulian, Lisa; Gengeliczki, Zsolt; Nachtigallova, Dana; Hobza, Pavel; deVries, Mattanjah

2011-01-01

We use multiphoton ionization and double resonance spectroscopy to study the excited state dynamics of biologically relevant molecules as well as prebiotic nucleobases, isolated in the gas phase. Molecules that are biologically relevant to life today tend to exhibit short excited state lifetimes compared to similar but non-biologically relevant analogs. The mechanism is internal conversion, which may help protect the biologically active molecules from UV damage. This process is governed by conical intersections that depend very strongly on molecular structure. Therefore we have studied purines and pyrimidines with systematic variations of structure, including substitutions, tautomeric forms, and cluster structures that represent different base pair binding motifs. These structural variations also include possible alternate base pairs that may shed light on prebiotic chemistry. With this in mind we have begun to probe the ultrafast dynamics of molecules that exhibit very short excited states and search for evidence of internal conversions.

Biosensor Recognition Elements

DTIC Science & Technology

2008-01-01

Systematics, bioinformatics, systems biology, regulation, genetics, genomics, metabolism, ecology, development . Epstein - Barr Virus Latency and...and C, Simian immunodeficiency, Ebola, Rabies, Epstein – Barr , and Measles viruses as well as biological agents such as botulinum neurotoxin A/B...time metabolic vigilance via sensor based ligand specific biorecognition elements is immense. Virus -based nanoparticles have been developed for

47 CFR 69.118 - Traffic sensitive switched services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Docket 86-10, FCC 93-53 (1993). Moreover, all customers that use basic 800 database service shall be... account revenues from the relevant Basic Service Element or Elements and 800 Database Service Elements in...

47 CFR 69.118 - Traffic sensitive switched services.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Docket 86-10, FCC 93-53 (1993). Moreover, all customers that use basic 800 database service shall be... account revenues from the relevant Basic Service Element or Elements and 800 Database Service Elements in...

47 CFR 69.118 - Traffic sensitive switched services.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Docket 86-10, FCC 93-53 (1993). Moreover, all customers that use basic 800 database service shall be... account revenues from the relevant Basic Service Element or Elements and 800 Database Service Elements in...

47 CFR 69.118 - Traffic sensitive switched services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Docket 86-10, FCC 93-53 (1993). Moreover, all customers that use basic 800 database service shall be... account revenues from the relevant Basic Service Element or Elements and 800 Database Service Elements in...

47 CFR 69.118 - Traffic sensitive switched services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Docket 86-10, FCC 93-53 (1993). Moreover, all customers that use basic 800 database service shall be... account revenues from the relevant Basic Service Element or Elements and 800 Database Service Elements in...

Defining scaffold geometries for interacting with proteins: geometrical classification of secondary structure linking regions.

PubMed

Tran, Tran T; Kulis, Christina; Long, Steven M; Bryant, Darryn; Adams, Peter; Smythe, Mark L

2010-11-01

Medicinal chemists synthesize arrays of molecules by attaching functional groups to scaffolds. There is evidence suggesting that some scaffolds yield biologically active molecules more than others, these are termed privileged substructures. One role of the scaffold is to present its side-chains for molecular recognition, and biologically relevant scaffolds may present side-chains in biologically relevant geometries or shapes. Since drug discovery is primarily focused on the discovery of compounds that bind to proteinaceous targets, we have been deciphering the scaffold shapes that are used for binding proteins as they reflect biologically relevant shapes. To decipher the scaffold architecture that is important for binding protein surfaces, we have analyzed the scaffold architecture of protein loops, which are defined in this context as continuous four residue segments of a protein chain that are not part of an α-helix or β-strand secondary structure. Loops are an important molecular recognition motif of proteins. We have found that 39 clusters reflect the scaffold architecture of 89% of the 23,331 loops in the dataset, with average intra-cluster and inter-cluster RMSD of 0.47 and 1.91, respectively. These protein loop scaffolds all have distinct shapes. We have used these 39 clusters that reflect the scaffold architecture of protein loops as biological descriptors. This involved generation of a small dataset of scaffold-based peptidomimetics. We found that peptidomimetic scaffolds with reported biological activities matched loop scaffold geometries and those peptidomimetic scaffolds with no reported biologically activities did not. This preliminary evidence suggests that organic scaffolds with tight matches to the preferred loop scaffolds of proteins, implies the likelihood of the scaffold to be biologically relevant.

Defining scaffold geometries for interacting with proteins: geometrical classification of secondary structure linking regions

NASA Astrophysics Data System (ADS)

Tran, Tran T.; Kulis, Christina; Long, Steven M.; Bryant, Darryn; Adams, Peter; Smythe, Mark L.

2010-11-01

Medicinal chemists synthesize arrays of molecules by attaching functional groups to scaffolds. There is evidence suggesting that some scaffolds yield biologically active molecules more than others, these are termed privileged substructures. One role of the scaffold is to present its side-chains for molecular recognition, and biologically relevant scaffolds may present side-chains in biologically relevant geometries or shapes. Since drug discovery is primarily focused on the discovery of compounds that bind to proteinaceous targets, we have been deciphering the scaffold shapes that are used for binding proteins as they reflect biologically relevant shapes. To decipher the scaffold architecture that is important for binding protein surfaces, we have analyzed the scaffold architecture of protein loops, which are defined in this context as continuous four residue segments of a protein chain that are not part of an α-helix or β-strand secondary structure. Loops are an important molecular recognition motif of proteins. We have found that 39 clusters reflect the scaffold architecture of 89% of the 23,331 loops in the dataset, with average intra-cluster and inter-cluster RMSD of 0.47 and 1.91, respectively. These protein loop scaffolds all have distinct shapes. We have used these 39 clusters that reflect the scaffold architecture of protein loops as biological descriptors. This involved generation of a small dataset of scaffold-based peptidomimetics. We found that peptidomimetic scaffolds with reported biological activities matched loop scaffold geometries and those peptidomimetic scaffolds with no reported biologically activities did not. This preliminary evidence suggests that organic scaffolds with tight matches to the preferred loop scaffolds of proteins, implies the likelihood of the scaffold to be biologically relevant.

Optimization of biological sulfide removal in a CSTR bioreactor.

PubMed

Roosta, Aliakbar; Jahanmiri, Abdolhossein; Mowla, Dariush; Niazi, Ali; Sotoodeh, Hamidreza

2012-08-01

In this study, biological sulfide removal from natural gas in a continuous bioreactor is investigated for estimation of the optimal operational parameters. According to the carried out reactions, sulfide can be converted to elemental sulfur, sulfate, thiosulfate, and polysulfide, of which elemental sulfur is the desired product. A mathematical model is developed and was used for investigation of the effect of various parameters on elemental sulfur selectivity. The results of the simulation show that elemental sulfur selectivity is a function of dissolved oxygen, sulfide load, pH, and concentration of bacteria. Optimal parameter values are calculated for maximum elemental sulfur selectivity by using genetic algorithm as an adaptive heuristic search. In the optimal conditions, 87.76% of sulfide loaded to the bioreactor is converted to elemental sulfur.

[The determination of the natural content of chemical elements in human biological objects (liver, kidney, stomach) by mass spectrometry with inductively coupled plasma].

PubMed

Luzanova, I S; Svetlolobov, D Iu; Zorin, Iu V

2014-01-01

The objective of the present work was to continue the studies of the sites of concentration of the chemical elements corresponding to normal homeostasis in human biological objects by mass spectrometry with inductively coupled plasma. The study yielded the data on the natural content of 27 elements in the cadaveric liver, kidney, and stomach. It is recommended to use these findings as the reference parameters corresponding to normal homeostasis.

Structure and Dynamics of Type III Secretion Effector Protein ExoU As determined by SDSL-EPR Spectroscopy in Conjunction with De Novo Protein Folding

PubMed Central

2017-01-01

ExoU is a 74 kDa cytotoxin that undergoes substantial conformational changes as part of its function, that is, it has multiple thermodynamically stable conformations that interchange depending on its environment. Such flexible proteins pose unique challenges to structural biology: (1) not only is it often difficult to determine structures by X-ray crystallography for all biologically relevant conformations because of the flat energy landscape (2) but also experimental conditions can easily perturb the biologically relevant conformation. The first challenge can be overcome by applying orthogonal structural biology techniques that are capable of observing alternative, biologically relevant conformations. The second challenge can be addressed by determining the structure in the same biological state with two independent techniques under different experimental conditions. If both techniques converge to the same structural model, the confidence that an unperturbed biologically relevant conformation is observed increases. To this end, we determine the structure of the C-terminal domain of the effector protein, ExoU, from data obtained by electron paramagnetic resonance spectroscopy in conjunction with site-directed spin labeling and in silico de novo structure determination. Our protocol encompasses a multimodule approach, consisting of low-resolution topology sampling, clustering, and high-resolution refinement. The resulting model was compared with an ExoU model in complex with its chaperone SpcU obtained previously by X-ray crystallography. The two models converged to a minimal RMSD100 of 3.2 Å, providing evidence that the unbound structure of ExoU matches the fold observed in complex with SpcU. PMID:28691114

Regulation of Spatiotemporal Patterns by Biological Variability: General Principles and Applications to Dictyostelium discoideum

PubMed Central

Grace, Miriam; Hütt, Marc-Thorsten

2015-01-01

Spatiotemporal patterns often emerge from local interactions in a self-organizing fashion. In biology, the resulting patterns are also subject to the influence of the systematic differences between the system’s constituents (biological variability). This regulation of spatiotemporal patterns by biological variability is the topic of our review. We discuss several examples of correlations between cell properties and the self-organized spatiotemporal patterns, together with their relevance for biology. Our guiding, illustrative example will be spiral waves of cAMP in a colony of Dictyostelium discoideum cells. Analogous processes take place in diverse situations (such as cardiac tissue, where spiral waves occur in potentially fatal ventricular fibrillation) so a deeper understanding of this additional layer of self-organized pattern formation would be beneficial to a wide range of applications. One of the most striking differences between pattern-forming systems in physics or chemistry and those in biology is the potential importance of variability. In the former, system components are essentially identical with random fluctuations determining the details of the self-organization process and the resulting patterns. In biology, due to variability, the properties of potentially very few cells can have a driving influence on the resulting asymptotic collective state of the colony. Variability is one means of implementing a few-element control on the collective mode. Regulatory architectures, parameters of signaling cascades, and properties of structure formation processes can be "reverse-engineered" from observed spatiotemporal patterns, as different types of regulation and forms of interactions between the constituents can lead to markedly different correlations. The power of this biology-inspired view of pattern formation lies in building a bridge between two scales: the patterns as a collective state of a very large number of cells on the one hand, and the internal parameters of the single cells on the other. PMID:26562406

Rapid Parallel Screening for Strain Optimization

DTIC Science & Technology

2013-08-16

fermentation yields of industrially relevant biological compounds. Screening of the desired chemicals was completed previously. Microbes that can...reporter, and, 2) a yeast TAR cloning shuttle vector for transferring catabolic clusters to E. coli. 15. SUBJECT TERMS NA 16. SECURITY CLASSIFICATION OF... fermentation yields of industrially relevant biological compounds. Screening of the desired chemicals was completed previously. Microbes that can utilize

Rapid Parallel Screening for Strain Optimization

DTIC Science & Technology

2013-05-16

fermentation yields of industrially relevant biological compounds. Screening of the desired chemicals was completed previously. Microbes that can...reporter, and, 2) a yeast TAR cloning shuttle vector for transferring catabolic clusters to E. coli. 15. SUBJECT TERMS NA 16. SECURITY CLASSIFICATION OF... fermentation yields of industrially relevant biological compounds. Screening of the desired chemicals was completed previously. Microbes that can utilize

Comparative Evaluation of Two Serial Gene Expression Experiments | Division of Cancer Prevention

Cancer.gov

Stuart G. Baker, 2014 Introduction This program fits biologically relevant response curves in comparative analysis of the two gene expression experiments involving same genes but under different scenarios and at least 12 responses. The program outputs gene pairs with biologically relevant response curve shapes including flat, linear, sigmoid, hockey stick, impulse and step

Biological monitoring of welders' exposure to chromium, molybdenum, tungsten and vanadium.

PubMed

Ellingsen, Dag G; Chashchin, Maxim; Berlinger, Balazs; Fedorov, Vladimir; Chashchin, Valery; Thomassen, Yngvar

2017-05-01

Welders are exposed to a number of metallic elements during work. Bioaccessability, that is important for element uptake, has been little studied. This study addresses bioaccessability and uptake of chromium (Cr), molybdenum (Mo), tungsten (W) and vanadium (V) among welders. Bioaccessability of Cr, Mo, V and W was studied in airborne particulate matter collected by personal sampling of the workroom air among shipyard welders by using the lung lining fluid simulant Hatch solution. Associations between concentrations of Hatch soluble and non-soluble elements (Hatch sol and Hatch non-sol ) and concentrations of the four elements in whole blood, serum, blood cells and urine were studied. Air concentrations of the four elements were low. Only a small fraction of Cr, V and W was Hatch sol , while similar amounts of Mo were Hatch sol and Hatch non-sol . Welders (N=70) had statistically significantly higher concentrations of all four elements in urine and serum when compared to referents (N=74). Highly statistically significant associations were observed between urinary W and Hatch sol W (p<0.001) and serum V and Hatch sol V (p<0.001), in particular when air samples collected the day before collection of biological samples were considered. Associations between Hatch sol elements in air and their biological concentrations were higher than when Hatch non-sol concentrations were considered. Associations were generally higher when air samples collected the day before biological sampling were considered as compared to air samples collected two days before. Copyright © 2017 Elsevier GmbH. All rights reserved.

Polarization-Modulated Second Harmonic Generation Microscopy in Collagen

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

Stoller, P C

Collagen is a key structural protein in the body; several pathological conditions lead to changes in collagen. Among imaging modalities that can be used in vivo, second harmonic generation (SHG) microscopy has a key advantage: it provides {approx}1 {micro}m resolution information about collagen structure as a function of depth. A new technique--polarization-modulated SHG--is presented: it permits simultaneous measurement of collagen orientation, of a lower bound on the magnitude of the second order nonlinear susceptibility tensor, and of the ratio of the two independent elements in this tensor. It is applied to characterizing SHG in collagen and to determining effects ofmore » biologically relevant changes in collagen structure. The magnitude of the second harmonic signal in two dimensional images varies with position even in structurally homogeneous tissue; this phenomenon is due to interference between second harmonic light generated by neighboring fibrils, which are randomly oriented parallel or anti-parallel to each other. Studies in which focal spot size was varied indicated that regions where fibrils are co-oriented are less than {approx}1.5 {micro}m in diameter. A quartz reference was used to determine the spot size as well as a lower limit (d{sub xxx} > 0.3 pm/V) for the magnitude of the second order nonlinear susceptibility. The ratio of the two independent tensor elements ranged between d{sub XYY}/d{sub XXX} = 0.60 and 0.75. SHG magnitude alone was not useful for identifying structural anomalies in collagenous tissue. Instead, changes in the polarization dependence of SHG were used to analyze biologically relevant perturbations in collagen structure. Changes in polarization dependence were observed in dehydrated samples, but not in highly crosslinked samples, despite significant alterations in packing structure. Complete thermal denaturation and collagenase digestion produced samples with no detectable SHG signal. Collagen orientation was measured in thin samples of several different tissues in transmission mode as well as at different depths (up to 200 {micro}m) in thick samples in reflection mode; birefringence had no effect on the measurement. These studies showed that SHG microscopy was capable of detecting pathophysiological changes in collagen structure, suggesting that this technique has potential clinical applications.« less

On the mechanics of growing thin biological membranes

NASA Astrophysics Data System (ADS)

Rausch, Manuel K.; Kuhl, Ellen

2014-02-01

Despite their seemingly delicate appearance, thin biological membranes fulfill various crucial roles in the human body and can sustain substantial mechanical loads. Unlike engineering structures, biological membranes are able to grow and adapt to changes in their mechanical environment. Finite element modeling of biological growth holds the potential to better understand the interplay of membrane form and function and to reliably predict the effects of disease or medical intervention. However, standard continuum elements typically fail to represent thin biological membranes efficiently, accurately, and robustly. Moreover, continuum models are typically cumbersome to generate from surface-based medical imaging data. Here we propose a computational model for finite membrane growth using a classical midsurface representation compatible with standard shell elements. By assuming elastic incompressibility and membrane-only growth, the model a priori satisfies the zero-normal stress condition. To demonstrate its modular nature, we implement the membrane growth model into the general-purpose non-linear finite element package Abaqus/Standard using the concept of user subroutines. To probe efficiently and robustness, we simulate selected benchmark examples of growing biological membranes under different loading conditions. To demonstrate the clinical potential, we simulate the functional adaptation of a heart valve leaflet in ischemic cardiomyopathy. We believe that our novel approach will be widely applicable to simulate the adaptive chronic growth of thin biological structures including skin membranes, mucous membranes, fetal membranes, tympanic membranes, corneoscleral membranes, and heart valve membranes. Ultimately, our model can be used to identify diseased states, predict disease evolution, and guide the design of interventional or pharmaceutic therapies to arrest or revert disease progression.

On the mechanics of growing thin biological membranes

PubMed Central

Rausch, Manuel K.; Kuhl, Ellen

2013-01-01

Despite their seemingly delicate appearance, thin biological membranes fulfill various crucial roles in the human body and can sustain substantial mechanical loads. Unlike engineering structures, biological membranes are able to grow and adapt to changes in their mechanical environment. Finite element modeling of biological growth holds the potential to better understand the interplay of membrane form and function and to reliably predict the effects of disease or medical intervention. However, standard continuum elements typically fail to represent thin biological membranes efficiently, accurately, and robustly. Moreover, continuum models are typically cumbersome to generate from surface-based medical imaging data. Here we propose a computational model for finite membrane growth using a classical midsurface representation compatible with standard shell elements. By assuming elastic incompressibility and membrane-only growth, the model a priori satisfies the zero-normal stress condition. To demonstrate its modular nature, we implement the membrane growth model into the general-purpose non-linear finite element package Abaqus/Standard using the concept of user subroutines. To probe efficiently and robustness, we simulate selected benchmark examples of growing biological membranes under different loading conditions. To demonstrate the clinical potential, we simulate the functional adaptation of a heart valve leaflet in ischemic cardiomyopathy. We believe that our novel approach will be widely applicable to simulate the adaptive chronic growth of thin biological structures including skin membranes, mucous membranes, fetal membranes, tympanic membranes, corneoscleral membranes, and heart valve membranes. Ultimately, our model can be used to identify diseased states, predict disease evolution, and guide the design of interventional or pharmaceutic therapies to arrest or revert disease progression. PMID:24563551

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

PubMed

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

2012-07-01

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.

Sociability modifies dogs' sensitivity to biological motion of different social relevance.

PubMed

Ishikawa, Yuko; Mills, Daniel; Willmott, Alexander; Mullineaux, David; Guo, Kun

2018-03-01

Preferential attention to living creatures is believed to be an intrinsic capacity of the visual system of several species, with perception of biological motion often studied and, in humans, it correlates with social cognitive performance. Although domestic dogs are exceptionally attentive to human social cues, it is unknown whether their sociability is associated with sensitivity to conspecific and heterospecific biological motion cues of different social relevance. We recorded video clips of point-light displays depicting a human or dog walking in either frontal or lateral view. In a preferential looking paradigm, dogs spontaneously viewed 16 paired point-light displays showing combinations of normal/inverted (control condition), human/dog and frontal/lateral views. Overall, dogs looked significantly longer at frontal human point-light display versus the inverted control, probably due to its clearer social/biological relevance. Dogs' sociability, assessed through owner-completed questionnaires, further revealed that low-sociability dogs preferred the lateral point-light display view, whereas high-sociability dogs preferred the frontal view. Clearly, dogs can recognize biological motion, but their preference is influenced by their sociability and the stimulus salience, implying biological motion perception may reflect aspects of dogs' social cognition.

Silvics of North America: 1. Conifers; 2. Hardwoods

Treesearch

Russell M. Burns; Barbara H. (tech. Coords.) Honkala

1990-01-01

The total environment of a tree is a complex integration of physical and biological elements. The physical elements are related to climate and soil and include radiation, precipitation, and the movement and composition of air; as well as the texture of the soil and its structure, depth, moisture capacity, drainage, nutrient content, and topographic position. Biological...

Biological X-ray absorption spectroscopy (BioXAS): a valuable tool for the study of trace elements in the life sciences.

PubMed

Strange, Richard W; Feiters, Martin C

2008-10-01

Using X-ray absorption spectroscopy (XAS) the binding modes (type and number of ligands, distances and geometry) and oxidation states of metals and other trace elements in crystalline as well as non-crystalline samples can be revealed. The method may be applied to biological systems as a 'stand-alone' technique, but it is particularly powerful when used alongside other X-ray and spectroscopic techniques and computational approaches. In this review, we highlight how biological XAS is being used in concert with crystallography, spectroscopy and computational chemistry to study metalloproteins in crystals, and report recent applications on relatively rare trace elements utilised by living organisms and metals involved in neurodegenerative diseases.

Physical, chemical, and biological data for detailed study of the Sun River Irrigation Project, Freezout Lake Wildlife Management Area, and Benton Lake National Wildlife Refuge, west-central Montana, 1990-92, with selected data for 1987-89

USGS Publications Warehouse

Lambing, J.H.; Nimick, D.A.; Knapton, J.R.; Palawski, D.U.

1994-01-01

Physical chemical, and biological data were collected in the lower Sun River area of west-central Montana during 1990-92 as part of a U.S. Department of the Interior detailed study of the extent, magnitude, sources, and potential biological impacts of contaminants associated with irrigation drainage. Physical and chemical data were collected from areas within and near the Sun River Irrigation Project and from wetland areas receiving irrigation drainage. Biological data were collected from areas in and near Freezout Lake Wildlife Management Area and Benton Lake National Wildlife Refuge. Additional biological data were collected previously during 1987-89 as part of a U.S. Fish and Wildlife Service program. This report presents data for selenium and other potentially toxic constituents in solid-phase, water, and biological media. Data consist of concentrations of major and trace elements in soil and drill cores; concen- trations of major ions, nutrients, and trace elements in ground water and surface water; and trace-element concentrations in bottom sediment and biological tissue. Hydrogeologic data for domestic and test wells and daily streamflow data for selected sites also are included.

Ion pump as Brownian motor: theory of electroconformational coupling and proof of ratchet mechanism for Na,K-ATPase action

NASA Astrophysics Data System (ADS)

Tsong, Tian Yow; Chang, Cheng-Hung

2003-04-01

This article reviews some concepts of the Brownian Ratchet which are relevant to our discussion of mechanisms of action of Na,K-ATPase, a universal ion pump and an elemental motor protein of the biological cell. Under wide ranges of ionic compositions it can hydrolyze an ATP and use the γ-phosphorous bond energy of ATP to pump 3 Na + out of, and 2 K + into the cell, both being uphill transport. During the ATP-dependent pump cycle, the enzyme oscillates between E1 and E2 states. Our experiment replaces ATP with externally applied electric field of various waveforms, amplitudes, and frequencies. The field enforced-oscillation, or fluctuation of E1 and E2 states enables the enzyme to harvest energy from the applied field and convert it to the chemical gradient energy of cations. A theory of electroconformational coupling (TEC), which embodies all the essential features of the Brownian Ratchet, successfully simulates these experimental results. Our analysis based on a four-state TEC model indicates that the equilibrium and the rate constants of the transport system define the frequency and the amplitude of the field for the optimal activation. Waveform, frequency, and amplitude are three elements of signal. Thus, electric signal of the ion pump is found by TEC analysis of the experimental data. Electric noise (white) superimposed on an electric signal changes the pump efficiency and produces effects similar to the stochastic resonance reported in other biological systems. The TEC concept is compared with the most commonly used Michaelis-Menten enzyme mechanism (MME) for similarities and differences. Both MME and TEC are catalytic wheels, which recycle the catalyst in each turnover. However, a MME can only catalyze reaction of descending free energy while a TEC enzyme can catalyze reaction of ascending free energy by harvesting needed energy from an off-equilibrium electric noise. The TEC mechanism is shown to be applicable to other biological motors and engines, as well. Deterministic and non-deterministic noise is examined in reference to future extension of the TEC model for biological transduction of free energy.

Biological Relevance of Key Events (KE) in utero in The Androgen Adverse Outcome Pathway Network (AOPn) to Adverse Effects in F1 Male Rats

EPA Science Inventory

We are conducting studies to evaluate the biological relevance of changes in KEs and molecular initiating events (MIE) in AOPs to determine if these can accurately predict of the dose levels of chemicals that disrupt the androgen signaling pathway in utero. Herein, we focus on ch...

Interactive Effects of Working Memory Self-Regulatory Ability and Relevance Instructions on Text Processing

ERIC Educational Resources Information Center

Hamilton, Nancy Jo

2012-01-01

Reading is a process that requires the enactment of many cognitive processes. Each of these processes uses a certain amount of working memory resources, which are severely constrained by biology. More efficiency in the function of working memory may mediate the biological limits of same. Reading relevancy instructions may be one such method to…

Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity

PubMed Central

Henegar, Corneliu; Tordjman, Joan; Achard, Vincent; Lacasa, Danièle; Cremer, Isabelle; Guerre-Millo, Michèle; Poitou, Christine; Basdevant, Arnaud; Stich, Vladimir; Viguerie, Nathalie; Langin, Dominique; Bedossa, Pierre; Zucker, Jean-Daniel; Clement, Karine

2008-01-01

Background Investigations performed in mice and humans have acknowledged obesity as a low-grade inflammatory disease. Several molecular mechanisms have been convincingly shown to be involved in activating inflammatory processes and altering cell composition in white adipose tissue (WAT). However, the overall importance of these alterations, and their long-term impact on the metabolic functions of the WAT and on its morphology, remain unclear. Results Here, we analyzed the transcriptomic signature of the subcutaneous WAT in obese human subjects, in stable weight conditions and after weight loss following bariatric surgery. An original integrative functional genomics approach was applied to quantify relations between relevant structural and functional themes annotating differentially expressed genes in order to construct a comprehensive map of transcriptional interactions defining the obese WAT. These analyses highlighted a significant up-regulation of genes and biological themes related to extracellular matrix (ECM) constituents, including members of the integrin family, and suggested that these elements could play a major mediating role in a chain of interactions that connect local inflammatory phenomena to the alteration of WAT metabolic functions in obese subjects. Tissue and cellular investigations, driven by the analysis of transcriptional interactions, revealed an increased amount of interstitial fibrosis in obese WAT, associated with an infiltration of different types of inflammatory cells, and suggest that phenotypic alterations of human pre-adipocytes, induced by a pro-inflammatory environment, may lead to an excessive synthesis of ECM components. Conclusion This study opens new perspectives in understanding the biology of human WAT and its pathologic changes indicative of tissue deterioration associated with the development of obesity. PMID:18208606

Evidence of transcranial direct current stimulation-generated electric fields at subthalamic level in human brain in vivo.

PubMed

Chhatbar, Pratik Y; Kautz, Steven A; Takacs, Istvan; Rowland, Nathan C; Revuelta, Gonzalo J; George, Mark S; Bikson, Marom; Feng, Wuwei

2018-03-13

Transcranial direct current stimulation (tDCS) is a promising brain modulation technique for several disease conditions. With this technique, some portion of the current penetrates through the scalp to the cortex and modulates cortical excitability, but a recent human cadaver study questions the amount. This insufficient intracerebral penetration of currents may partially explain the inconsistent and mixed results in tDCS studies to date. Experimental validation of a transcranial alternating current stimulation-generated electric field (EF) in vivo has been performed on the cortical (using electrocorticography, ECoG, electrodes), subcortical (using stereo electroencephalography, SEEG, electrodes) and deeper thalamic/subthalamic levels (using DBS electrodes). However, tDCS-generated EF measurements have never been attempted. We aimed to demonstrate that tDCS generates biologically relevant EF as deep as the subthalamic level in vivo. Patients with movement disorders who have implanted deep brain stimulation (DBS) electrodes serve as a natural experimental model for thalamic/subthalamic recordings of tDCS-generated EF. We measured voltage changes from DBS electrodes and body resistance from tDCS electrodes in three subjects while applying direct current to the scalp at 2 mA and 4 mA over two tDCS montages. Voltage changes at the level of deep nuclei changed proportionally with the level of applied current and varied with different tDCS montages. Our findings suggest that scalp-applied tDCS generates biologically relevant EF. Incorporation of these experimental results may improve finite element analysis (FEA)-based models. Copyright © 2018 Elsevier Inc. All rights reserved.

Exposure to Pb, Cd, and As mixtures potentiates the production of oxidative stress precursors: 30-day, 90-day, and 180-day drinking water studies in rats.

PubMed

Whittaker, Margaret H; Wang, Gensheng; Chen, Xue-Qing; Lipsky, Michael; Smith, Donald; Gwiazda, Roberto; Fowler, Bruce A

2011-07-15

Exposure to chemical mixtures is a common and important determinant of toxicity and is of particular concern due to their appearance in sources of drinking water. Despite this, few in vivo mixture studies have been conducted to date to understand the health impact of chemical mixtures compared to single chemicals. Interactive effects of lead (Pb), cadmium (Cd) and arsenic (As) were evaluated in 30-, 90-, and 180-day factorial design drinking water studies in rats designed to test the hypothesis that ingestion of such mixtures at individual component Lowest-Observed-Effect-Levels (LOELs) results in increased levels of the pro-oxidant delta aminolevulinic acid (ALA), iron, and copper. LOEL levels of Pb, Cd, and As mixtures resulted in the increased presence of mediators of oxidative stress such as ALA, copper, and iron. ALA increases were followed by statistically significant increases in kidney copper in the 90- and 180-day studies. Statistical evidence of interaction was identified for six biologically relevant variables: blood delta aminolevulinic acid dehydratase (ALAD), kidney ALAD, urinary ALA, urinary iron, kidney iron, and kidney copper. The current investigations underscore the importance of considering interactive effects that common toxic agents such as Pb, Cd, and As may have upon one another at low-dose levels. The interactions between known toxic trace elements at biologically relevant concentrations shown here demonstrate a clear need to rigorously review methods by which national/international agencies assess health risks of chemicals, since exposures may commonly occur as complex mixtures. Copyright © 2011. Published by Elsevier Inc.

Biological and Environmental Transformations of Copper-Based Nanomaterials

PubMed Central

Wang, Zhongying; Von Dem Bussche, Annette; Kabadi, Pranita K.; Kane, Agnes B.; Hurt, Robert H.

2013-01-01

Copper-based nanoparticles are an important class of materials with applications as catalysts, conductive inks, and antimicrobial agents. Environmental and safety issues are particularly important for copper-based nanomaterials because of their potential large-scale use and their high redox activity and toxicity reported from in vitro studies. Elemental nanocopper oxidizes readily upon atmospheric exposure during storage and use, so copper oxides are highly relevant phases to consider in studies of environmental and health impacts. Here we show that copper oxide nanoparticles undergo profound chemical transformations under conditions relevant to living systems and the natural environment. Copper oxide nanoparticle (CuO-NP) dissolution occurs at lysosomal pH (4-5), but not at neutral pH in pure water. Despite the near-neutral pH of cell culture medium, CuO-NPs undergo significant dissolution in media over time scales relevant to toxicity testing due to ligand-assisted ion release, in which amino acid complexation is an important contributor. Electron paramagnetic resonance (EPR) spectroscopy shows that dissolved copper in association with CuO-NPs are the primary redox-active species. CuO-NPs also undergo sulfidation by a dissolution-reprecipitation mechanism, and the new sulfide surfaces act as catalysts for sulfide oxidation. Copper sulfide NPs are found to be much less cytotoxic than CuO NPs, which is consistent with the very low solubility of CuS. Despite this low solubility of CuS, EPR studies show that sulfidated CuO continues to generate some ROS activity due to the release of free copper by H2O2 oxidation during the Fenton-chemistry-based EPR assay. While sulfidation can serve as a natural detoxification process for nanosilver and other chalcophile metals, our results suggest that sulfidation may not fully and permanently detoxify copper in biological or environmental compartments that contain reactive oxygen species. PMID:24032665

Nuclear physics from Lattice QCD

NASA Astrophysics Data System (ADS)

Shanahan, Phiala

2017-09-01

I will discuss the current state and future scope of numerical Lattice Quantum Chromodynamics (LQCD) calculations of nuclear matrix elements. The goal of the program is to provide direct QCD calculations of nuclear observables relevant to experimental programs, including double-beta decay matrix elements, nuclear corrections to axial matrix elements relevant to long-baseline neutrino experiments and nuclear sigma terms needed for theory predictions of dark matter cross-sections at underground detectors. I will discuss the progress and challenges on these fronts, and also address recent work constraining a gluonic analogue of the EMC effect, which will be measurable at a future electron-ion collider.

Reconstructing the evolution of first-row transition metal minerals by GeoDeepDive

NASA Astrophysics Data System (ADS)

Liu, C.; Peters, S. E.; Ross, I.; Golden, J. J.; Downs, R. T.; Hazen, R. M.

2016-12-01

Terrestrial mineralogy evolves as a consequence of a range of physical, chemical, and biological processes [1]. Evolution of the first-row transition metal minerals could mirror the evolution of Earth's oxidation state and life, since these elements mostly are redox-sensitive and/or play critical roles in biology. The fundamental building blocks to reconstruct mineral evolution are the mineral species, locality, and age data, which are typically dispersed in sentences in scientific and technical publications. These data can be tracked down in a brute-force way, i.e., human retrieval, reading, and recording all relevant literature. Alternatively, they can be extracted automatically by GeoDeepDive. In GeoDeepDive, scientific and technical articles from publishers, including Elsevier, Wiley, USGS, SEPM, GSA and Canada Science Publishing, have been parsed into a Javascript database with NLP tags. Sentences containing data of mineral names, locations, and ages can be recognized and extracted by user-developed applications. In a preliminary search for cobalt mineral ages, we successfully extracted 678 citations with >1000 mentions of cobalt minerals, their locations, and ages. The extracted results are in agreement with brute-force search results. What is more, GeoDeepDive provides 40 additional data points that were not recovered by the brute-force approach. The extracted mineral locality-age data suggest that the evolution of Co minerals is controlled by global supercontinent cycles, i.e., more Co minerals form during episodes of supercontinent assembly. Mineral evolution of other first-row transition elements is being investigated through GeoDeepDive. References: [1] Hazen et al. (2008) Mineral evolution. American Mineralogist, 93, 1693-1720

Towards molecular medicine: a case for a biological periodic table.

PubMed

Gawad, Charles

2005-01-01

The recently amplified pace of development in the technologies to study both normal and aberrant cellular physiology has allowed for a transition from the traditional reductionist approaches to global interrogations of human biology. This transformation has created the anticipation that we will soon more effectively treat or contain most types of diseases through a 'systems-based' approach to understanding and correcting the underlying etiology of these processes. However, to accomplish these goals, we must first have a more comprehensive understanding of all the elements involved in human cellular physiology, as well as why and how they interact. With the vast number of biological components that have and are being discovered, creating methods with modern computational techniques to better organize biological elements is the next requisite step in this process. This article aims to articulate the importance of the organization of chemical elements into a periodic table had on the conversion of chemistry into a quantitative, translatable science, as well as how we can apply the lessons learned in that transition to the current transformation taking place in biology.

Abasy Atlas: a comprehensive inventory of systems, global network properties and systems-level elements across bacteria

PubMed Central

Ibarra-Arellano, Miguel A.; Campos-González, Adrián I.; Treviño-Quintanilla, Luis G.; Tauch, Andreas; Freyre-González, Julio A.

2016-01-01

The availability of databases electronically encoding curated regulatory networks and of high-throughput technologies and methods to discover regulatory interactions provides an invaluable source of data to understand the principles underpinning the organization and evolution of these networks responsible for cellular regulation. Nevertheless, data on these sources never goes beyond the regulon level despite the fact that regulatory networks are complex hierarchical-modular structures still challenging our understanding. This brings the necessity for an inventory of systems across a large range of organisms, a key step to rendering feasible comparative systems biology approaches. In this work, we take the first step towards a global understanding of the regulatory networks organization by making a cartography of the functional architectures of diverse bacteria. Abasy (Across-bacteria systems) Atlas provides a comprehensive inventory of annotated functional systems, global network properties and systems-level elements (global regulators, modular genes shaping functional systems, basal machinery genes and intermodular genes) predicted by the natural decomposition approach for reconstructed and meta-curated regulatory networks across a large range of bacteria, including pathogenically and biotechnologically relevant organisms. The meta-curation of regulatory datasets provides the most complete and reliable set of regulatory interactions currently available, which can even be projected into subsets by considering the force or weight of evidence supporting them or the systems that they belong to. Besides, Abasy Atlas provides data enabling large-scale comparative systems biology studies aimed at understanding the common principles and particular lifestyle adaptions of systems across bacteria. Abasy Atlas contains systems and system-level elements for 50 regulatory networks comprising 78 649 regulatory interactions covering 42 bacteria in nine taxa, containing 3708 regulons and 1776 systems. All this brings together a large corpus of data that will surely inspire studies to generate hypothesis regarding the principles governing the evolution and organization of systems and the functional architectures controlling them. Database URL: http://abasy.ccg.unam.mx PMID:27242034

The Biology of Cancer Health Disparities

Cancer.gov

These examples show how biology contributes to health disparities (differences in disease incidence and outcomes among distinct racial and ethnic groups, ), and how biological factors interact with other relevant factors, such as diet and the environment.

Modulating biological events by biophysics: an innovative molecular methodology using ion cyclotron resonance--a pilot study.

PubMed

Corbellini, Ezio; Corbellini, Monica; Licciardello, Orazio; Marotta, Francesco

2014-04-01

The QUEC PHISIS(™) technology, based on the theory of coherence domains of water, is the most advanced application of quantum electrodynamics coherence suitable for transferring highly targeted and personalized electromagnetic signals to the living cells. Several experimental studies in aged rats confirm its beneficial action on vital cellular parameters while also optimizing the bioavailability and absorption of fundamental elements in cellular metabolism. Clinical observations have followed and have strengthened its applicability in healthy volunteers and in patients with complex diseases such as cardiovascular, neuromuscular, and metabolic disorders. Our pilot study on severely compromised, frail subjects corroborates its relevance. The delivery of correct frequencies has the potential to become a safe, very affordable, and effective therapeutic modality that is amenable to being integrated with pharmacological drugs, thus representing a substantial innovation in medical practice.

The B1 Protein Guides the Biosynthesis of a Lasso Peptide

NASA Astrophysics Data System (ADS)

Zhu, Shaozhou; Fage, Christopher D.; Hegemann, Julian D.; Mielcarek, Andreas; Yan, Dushan; Linne, Uwe; Marahiel, Mohamed A.

2016-10-01

Lasso peptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) with a unique lariat knot-like fold that endows them with extraordinary stability and biologically relevant activity. However, the biosynthetic mechanism of these fascinating molecules remains largely speculative. Generally, two enzymes (B for processing and C for cyclization) are required to assemble the unusual knot-like structure. Several subsets of lasso peptide gene clusters feature a “split” B protein on separate open reading frames (B1 and B2), suggesting distinct functions for the B protein in lasso peptide biosynthesis. Herein, we provide new insights into the role of the RiPP recognition element (RRE) PadeB1, characterizing its capacity to bind the paeninodin leader peptide and deliver its peptide substrate to PadeB2 for processing.

Genetics against race: Science, politics and affirmative action in Brazil.

PubMed

Kent, Michael; Wade, Peter

2015-12-01

This article analyses interrelations between genetic ancestry research, political conflict and social identity. It focuses on the debate on race-based affirmative action policies, which have been implemented in Brazil since the turn of the century. Genetic evidence of high levels of admixture in the Brazilian population has become a key element of arguments that question the validity of the category of race for the development of public policies. In response, members of Brazil's black movement have dismissed the relevance of genetics by arguing, first, that in Brazil race functions as a social--rather than a biological--category, and, second, that racial classification and discrimination in this country are based on appearance, rather than on genotype. This article highlights the importance of power relations and political interests in shaping public engagements with genetic research and their social consequences.

Intracellular distribution and stability of a luminescent rhenium(I) tricarbonyl tetrazolato complex using epifluorescence microscopy in conjunction with X-ray fluorescence imaging

DOE PAGES

Wedding, Jason L.; Harris, Hugh H.; Bader, Christie A.; ...

2016-11-23

Optical fluorescence microscopy was used in conjunction with X-ray fluorescence microscopy to monitor the stability and intracellular distribution of the luminescent rhenium(I) complex fac-[Re(CO) 3(phen)L], where phen = 1,10-phenathroline and L = 5-(4-iodophenyl)tetrazolato, in 22Rv1 cells. The rhenium complex showed no signs of ancillary ligand dissociation, a conclusion based on data obtained via X-ray fluorescence imaging aligning iodine and rhenium distributions. A diffuse reticular localisation was detected for the complex, in the nuclear/perinuclear region of cells, by either optical or X-ray fluorescence techniques. Furthermore, X-ray fluorescence also showed that the Re-I complex disrupted the homeostasis of some biologically relevant elements,more » such as chlorine, potassium and zinc.« less

Periodic Table Target: A Game that Introduces the Biological Significance of Chemical Element Periodicity

ERIC Educational Resources Information Center

Sevcik, Richard S.; McGinty, Ragan L.; Schultz, Linda D.; Alexander, Susan V.

2008-01-01

Periodic Table Target, a game for middle school or high school students, familiarizes students with the form of the periodic table and the biological significance of different elements. The Periodic Table Target game board is constructed as a class project, and the game is played to reinforce the content. Students are assigned several elements…

Electron microprobe analysis program for biological specimens: BIOMAP

NASA Technical Reports Server (NTRS)

Edwards, B. F.

1972-01-01

BIOMAP is a Univac 1108 compatible program which facilitates the electron probe microanalysis of biological specimens. Input data are X-ray intensity data from biological samples, the X-ray intensity and composition data from a standard sample and the electron probe operating parameters. Outputs are estimates of the weight percentages of the analyzed elements, the distribution of these estimates for sets of red blood cells and the probabilities for correlation between elemental concentrations. An optional feature statistically estimates the X-ray intensity and residual background of a principal standard relative to a series of standards.

Ways of incorporating photographic images in learning and assessing high school biology: A study of visual perception and visual cognition

NASA Astrophysics Data System (ADS)

Nixon, Brenda Chaumont

This study evaluated the cognitive benefits and costs of incorporating biology-textbook and student-generated photographic images into the learning and assessment processes within a 10th grade biology classroom. The study implemented Wandersee's (2000) 20-Q Model of Image-Based Biology Test-Item Design (20-Q Model) to explore the use of photographic images to assess students' understanding of complex biological processes. A thorough review of the students' textbook using ScaleMaster R with PC Interface was also conducted. The photographs, diagrams, and other representations found in the textbook were measured to determine the percentage of each graphic depicted in the book and comparisons were made to the text. The theoretical framework that guided the research included Human Constructivist tenets espoused by Mintzes, Wandersee and Novak (2000). Physiological and cognitive factors of images and image-based learning as described by Robin (1992), Solso (1997) and Wandersee (2000) were examined. Qualitative case study design presented by Yin (1994), Denzin and Lincoln (1994) was applied and data were collected through interviews, observations, student activities, student and school artifacts and Scale Master IIRTM measurements. The results of the study indicate that although 24% of the high school biology textbook is devoted to photographic images which contribute significantly to textbook cost, the teacher and students paid little attention to photographic images other than as aesthetic elements for creating biological ambiance, wasting valuable opportunities for learning. The analysis of the photographs corroborated findings published by the Association American Association for the Advancement of Science that indicated "While most of the books are lavishly illustrated, these representations are rarely helpful, because they are too abstract, needlessly complicated, or inadequately explained" (Roseman, 2000, p. 2). The findings also indicate that applying the 20-Q Model to photographs in biology textbooks can (a) effectively assess students' understanding of complex biological concepts, (b) offer alternative assessment strategies that complement individual learning styles, (c) identify misconceptions, and (d) encourage students to practice metacognition. In addition, once students have learned how to interpret textbook images, application of that knowledge through self-generated biologically relevant digital or print images provides opportunities for increased conceptual understanding.

Systems biology, adverse outcome pathways, and ecotoxicology in the 21st century

EPA Science Inventory

While many definitions of systems biology exist, the majority of these contain most (if not all) of the following elements: global measurements of biological molecules to the extent technically feasible, dynamic measurements of key biological molecules to establish quantitative r...

In vivo CH3(CH2)11SAu SAM electrodes in the beating heart: in situ analytical studies relevant to pacemakers and interstitial biosensors.

PubMed

Chou, Howard A; Zavitz, Daniel H; Ovadia, Marc

2003-01-01

To study in vivo modification of the SAM equivalent circuit when a highly ordered SAM is used as a bioelectrode, dodecanethiolate SAM-Au intramuscular electrodes were studied in living rat heart in a challenging in situ perfused rat model by impedance spectroscopy, cyclic voltammetry, and neutron activation analysis (NAA). The SAM layer experienced disintegration in vivo biological system, as NAA detected the presence of Au atoms that had leached into the surrounding living tissue. Therefore, the underlying Au surface became exposed during biological implant. Study by impedance spectroscopy, however, revealed perfect capacitive behavior for the SAM, similar to in vitro behavior. Electrodes showed a pure capacitive Nyquist plot with 86.1-89.4 degrees near-vertical line segments as the equivalent circuit locus, as for a parallel plate capacitor. Impedance magnitude varied linearly with 1/omega excluding diffusionally limited ionic charge transport. There was no diffusional conductive element Z(W infinity ) or spatially confined Warburg impedance Z(D). The effect of in vivo exposure of a highly ordered SAM is a 'sealing over' effect of new defects by the binding of proteinaceous or lipid species in the biological milieu, a fact of significance for SAM electrodes used either as pacemaker electrodes or as a platform for in vivo biosensors.

Platinum nanoparticles: a non-toxic, effective and thermally stable alternative plasmonic material for cancer therapy and bioengineering.

PubMed

Samadi, Akbar; Klingberg, Henrik; Jauffred, Liselotte; Kjær, Andreas; Bendix, Poul Martin; Oddershede, Lene B

2018-05-17

Absorption of near infrared (NIR) light by metallic nanoparticles can cause extreme heating and is of interest for instance in cancer treatment since NIR light has a relatively large penetration depth into biological tissue. Here, we quantify the extraordinary thermoplasmonic properties of platinum nanoparticles and demonstrate their efficiency in photothermal cancer therapy. Although platinum nanoparticles are extensively used for catalysis, they are much overlooked in a biological context. Via direct measurements based on a biological matrix we show that individual irradiated platinum nanoparticles with diameters of 50-70 nm can easily reach surface temperatures up to 900 K. In contrast to gold nanoshells, which are often used for photothermal purposes, we demonstrate that the platinum particles remain stable at these extreme temperatures. The experiments are paralleled by finite element modeling confirming the experimental results and establishing a theoretical understanding of the particles' thermoplasmonic properties. At extreme temperatures it is likely that a vapor layer will form around the plasmonic particle, and we show this scenario to be consistent with direct measurements and simulations. Viability studies demonstrate that platinum nanoparticles themselves are non-toxic at therapeutically relevant concentrations, however, upon laser irradiation we show that they efficiently kill human cancer cells. Therefore, platinum nanoparticles are highly promising candidates for thermoplasmonic applications in the life sciences, in nano-medicine, and for bio-medical engineering.

Scoring clustering solutions by their biological relevance.

PubMed

Gat-Viks, I; Sharan, R; Shamir, R

2003-12-12

A central step in the analysis of gene expression data is the identification of groups of genes that exhibit similar expression patterns. Clustering gene expression data into homogeneous groups was shown to be instrumental in functional annotation, tissue classification, regulatory motif identification, and other applications. Although there is a rich literature on clustering algorithms for gene expression analysis, very few works addressed the systematic comparison and evaluation of clustering results. Typically, different clustering algorithms yield different clustering solutions on the same data, and there is no agreed upon guideline for choosing among them. We developed a novel statistically based method for assessing a clustering solution according to prior biological knowledge. Our method can be used to compare different clustering solutions or to optimize the parameters of a clustering algorithm. The method is based on projecting vectors of biological attributes of the clustered elements onto the real line, such that the ratio of between-groups and within-group variance estimators is maximized. The projected data are then scored using a non-parametric analysis of variance test, and the score's confidence is evaluated. We validate our approach using simulated data and show that our scoring method outperforms several extant methods, including the separation to homogeneity ratio and the silhouette measure. We apply our method to evaluate results of several clustering methods on yeast cell-cycle gene expression data. The software is available from the authors upon request.

Salubrious effects of oxytocin on social stress-induced deficits

PubMed Central

Smith, Adam S.; Wang, Zuoxin

2012-01-01

Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to mental and physical health. In contrast, social support can ameliorate stress-induced physiological and immunological deficits, reducing the risk of subsequent psychological distress and improving an individual's overall well-being. For better clinical treatment of these physiological and mental pathologies, it is necessary to understand the regulatory mechanisms of stress-induced pathologies as well as determine the underlying biological mechanisms that regulate social buffering of the stress system. A number of ethologically relevant animal models of social stress and species that form strong adult social bonds have been utilized to study the etiology, treatment, and prevention of stress-related disorders. While undoubtedly a number of biological pathways contribute to the social buffering of the stress response, the convergence of evidence denotes the regulatory effects of oxytocin in facilitating social bond-promoting behaviors and their effect on the stress response. Thus, oxytocin may be perceived as a common regulatory element of the social environment, stress response, and stress-induced risks on mental and physical health. PMID:22178036

PAGER 2.0: an update to the pathway, annotated-list and gene-signature electronic repository for Human Network Biology

PubMed Central

Yue, Zongliang; Zheng, Qi; Neylon, Michael T; Yoo, Minjae; Shin, Jimin; Zhao, Zhiying; Tan, Aik Choon

2018-01-01

Abstract Integrative Gene-set, Network and Pathway Analysis (GNPA) is a powerful data analysis approach developed to help interpret high-throughput omics data. In PAGER 1.0, we demonstrated that researchers can gain unbiased and reproducible biological insights with the introduction of PAGs (Pathways, Annotated-lists and Gene-signatures) as the basic data representation elements. In PAGER 2.0, we improve the utility of integrative GNPA by significantly expanding the coverage of PAGs and PAG-to-PAG relationships in the database, defining a new metric to quantify PAG data qualities, and developing new software features to simplify online integrative GNPA. Specifically, we included 84 282 PAGs spanning 24 different data sources that cover human diseases, published gene-expression signatures, drug–gene, miRNA–gene interactions, pathways and tissue-specific gene expressions. We introduced a new normalized Cohesion Coefficient (nCoCo) score to assess the biological relevance of genes inside a PAG, and RP-score to rank genes and assign gene-specific weights inside a PAG. The companion web interface contains numerous features to help users query and navigate the database content. The database content can be freely downloaded and is compatible with third-party Gene Set Enrichment Analysis tools. We expect PAGER 2.0 to become a major resource in integrative GNPA. PAGER 2.0 is available at http://discovery.informatics.uab.edu/PAGER/. PMID:29126216

Deciphering the Complex Chemistry of Deep-Ocean Particles Using Complementary Synchrotron X-ray Microscope and Microprobe Instruments.

PubMed

Toner, Brandy M; German, Christopher R; Dick, Gregory J; Breier, John A

2016-01-19

The reactivity and mobility of natural particles in aquatic systems have wide ranging implications for the functioning of Earth surface systems. Particles in the ocean are biologically and chemically reactive, mobile, and complex in composition. The chemical composition of marine particles is thought to be central to understanding processes that convert globally relevant elements, such as C and Fe, among forms with varying bioavailability and mobility in the ocean. The analytical tools needed to measure the complex chemistry of natural particles are the subject of this Account. We describe how a suite of complementary synchrotron radiation instruments with nano- and micrometer focusing, and X-ray absorption spectroscopy (XAS) and X-ray diffraction (XRD) capabilities are changing our understanding of deep-ocean chemistry and life. Submarine venting along mid-ocean ridges creates hydrothermal plumes where dynamic particle-forming reactions occur as vent fluids mix with deep-ocean waters. Whether plumes are net sources or sinks of elements in ocean budgets depends in large part on particle formation, reactivity, and transport properties. Hydrothermal plume particles have been shown to host microbial communities and exhibit complex size distributions, aggregation behavior, and composition. X-ray microscope and microprobe instruments can address particle size and aggregation, but their true strength is in measuring chemical composition. Plume particles comprise a stunning array of inorganic and organic phases, from single-crystal sulfides to poorly ordered nanophases and polymeric organic matrices to microbial cells. X-ray microscopes and X-ray microprobes with elemental imaging, XAS, and XRD capabilities are ideal for investigating these complex materials because they can (1) measure the chemistry of organic and inorganic constituents in complex matrices, usually within the same particle or aggregate, (2) provide strong signal-to-noise data with exceedingly small amounts of material, (3) simplify the chemical complexity of particles or sets of particles with a focused-beam, providing spatial resolution over 6 orders of magnitude (nanometer to millimeter), (4) provide elemental specificity for elements in the soft-, tender-, and hard-X-ray energies, (5) switch rapidly among elements of interest, and (6) function in the presence of water and gases. Synchrotron derived data sets are discussed in the context of important advances in deep-ocean technology, sample handling and preservation, molecular microbiology, and coupled physical-chemical-biological modeling. Particle chemistry, size, and morphology are all important in determining whether particles are reactive with dissolved constituents, provide substrates for microbial respiration and growth, and are delivered to marine sediments or dispersed by deep-ocean currents.

Morphomics: An integral part of systems biology of the human placenta.

PubMed

Mayhew, T M

2015-04-01

The placenta is a transient organ the functioning of which has health consequences far beyond the embryo/fetus. Understanding the biology of any system (organ, organism, single cell, etc) requires a comprehensive and inclusive approach which embraces all the biomedical disciplines and 'omic' technologies and then integrates information obtained from all of them. Among the latest 'omics' is morphomics. The terms morphome and morphomics have been applied incoherently in biology and biomedicine but, recently, they have been given clear and widescale definitions. Morphomics is placed in the context of other 'omics' and its pertinent technologies and tools for sampling and quantitation are reviewed. Emphasis is accorded to the importance of random sampling principles in systems biology and the value of combining 3D quantification with alternative imaging techniques to advance knowledge and understanding of the human placental morphome. By analogy to other 'omes', the morphome is the totality of morphological features within a system and morphomics is the systematic study of those structures. Information about structure is required at multiple levels of resolution in order to understand better the processes by which a given system alters with time, experimental treatment or environmental insult. Therefore, morphomics research includes all imaging techniques at all levels of achievable resolution from gross anatomy and medical imaging, via optical and electron microscopy, to molecular characterisation. Quantification is an important element of all 'omics' studies and, because biological systems exist and operate in 3-dimensional (3D) space, precise descriptions of form, content and spatial relationships require the quantification of structure in 3D. These considerations are relevant to future study contributions to the Human Placenta Project. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mapping of native inorganic elements and injected nanoparticles in a biological organ with laser-induced plasma

NASA Astrophysics Data System (ADS)

Motto-Ros, V.; Sancey, L.; Ma, Q. L.; Lux, F.; Bai, X. S.; Wang, X. C.; Yu, Jin; Panczer, G.; Tillement, O.

2012-11-01

Emission spectroscopy of laser-induced plasma from a thin section of mouse kidney successfully detected inorganic elements, Na, Ca, Cu, and Gd, naturally contained in the organ or artificially injected in the form of Gd-based nanoparticle. A two-dimensional scan of the sample allowed the laser beam to explore its surface with a resolution of 100 μm, resulting in a quantitative elemental mapping of the organ with sub-mM sensitivity. The compatibility of the setup with standard optical microscopy emphasizes the potential to provide multiple images of a same biological tissue with different types of response which can be elemental, molecular, or cellular.

An evolutionary ecology of individual differences

PubMed Central

Dall, Sasha R. X.; Bell, Alison M.; Bolnick, Daniel I.; Ratnieks, Francis L. W.

2014-01-01

Individuals often differ in what they do. This has been recognised since antiquity. Nevertheless, the ecological and evolutionary significance of such variation is attracting widespread interest, which is burgeoning to an extent that is fragmenting the literature. As a first attempt at synthesis, we focus on individual differences in behaviour within populations that exceed the day-to-day variation in individual behaviour (i.e. behavioural specialisation). Indeed, the factors promoting ecologically relevant behavioural specialisation within natural populations are likely to have far-reaching ecological and evolutionary consequences. We discuss such individual differences from three distinct perspectives: individual niche specialisations, the division of labour within insect societies and animal personality variation. In the process, while recognising that each area has its own unique motivations, we identify a number of opportunities for productive ‘crossfertilisation’ among the (largely independent) bodies of work. We conclude that a complete understanding of evolutionarily and ecologically relevant individual differences must specify how ecological interactions impact the basic biological process (e.g. Darwinian selection, development and information processing) that underpin the organismal features determining behavioural specialisations. Moreover, there is likely to be covariation amongst behavioural specialisations. Thus, we sketch the key elements of a general framework for studying the evolutionary ecology of individual differences. PMID:22897772

Biological Evidence Management for DNA Analysis in Cases of Sexual Assault

PubMed Central

Magalhães, Teresa; Dinis-Oliveira, Ricardo Jorge; Silva, Benedita; Corte-Real, Francisco; Nuno Vieira, Duarte

2015-01-01

Biological evidence with forensic interest may be found in several cases of assault, being particularly relevant if sexually related. Sexual assault cases are characterized by low rates of disclosure, reporting, prosecution, and conviction. Biological evidence is sometimes the only way to prove the occurrence of sexual contact and to identify the perpetrator. The major focus of this review is to propose practical approaches and guidelines to help health, forensic, and law enforcement professionals to deal with biological evidence for DNA analysis. Attention should be devoted to avoiding contamination, degradation, and loss of biological evidence, as well as respecting specific measures to properly handle evidence (i.e., selection, collection, packing, sealing, labeling, storage, preservation, transport, and guarantee of the chain custody). Biological evidence must be carefully managed since the relevance of any finding in Forensic Genetics is determined, in the first instance, by the integrity and quantity of the samples submitted for analysis. PMID:26587562

A finite elements method to solve the Bloch-Torrey equation applied to diffusion magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Nguyen, Dang Van; Li, Jing-Rebecca; Grebenkov, Denis; Le Bihan, Denis

2014-04-01

The complex transverse water proton magnetization subject to diffusion-encoding magnetic field gradient pulses in a heterogeneous medium can be modeled by the multiple compartment Bloch-Torrey partial differential equation (PDE). In addition, steady-state Laplace PDEs can be formulated to produce the homogenized diffusion tensor that describes the diffusion characteristics of the medium in the long time limit. In spatial domains that model biological tissues at the cellular level, these two types of PDEs have to be completed with permeability conditions on the cellular interfaces. To solve these PDEs, we implemented a finite elements method that allows jumps in the solution at the cell interfaces by using double nodes. Using a transformation of the Bloch-Torrey PDE we reduced oscillations in the searched-for solution and simplified the implementation of the boundary conditions. The spatial discretization was then coupled to the adaptive explicit Runge-Kutta-Chebyshev time-stepping method. Our proposed method is second order accurate in space and second order accurate in time. We implemented this method on the FEniCS C++ platform and show time and spatial convergence results. Finally, this method is applied to study some relevant questions in diffusion MRI.

A haptic sensor-actor-system based on ultrasound elastography and electrorheological fluids for virtual reality applications in medicine.

PubMed

Khaled, W; Ermert, H; Bruhns, O; Boese, H; Baumann, M; Monkman, G J; Egersdoerfer, S; Meier, A; Klein, D; Freimuth, H

2003-01-01

Mechanical properties of biological tissue represent important diagnostic information and are of histological relevance (hard lesions, "nodes" in organs: tumors; calcifications in vessels: arteriosclerosis). The problem is, that such information is usually obtained by digital palpation only, which is limited with respect to sensitivity. It requires intuitive assessment and does not allow quantitative documentation. A suitable sensor is required for quantitative detection of mechanical tissue properties. On the other hand, there is also some need for a realistic mechanical display of those tissue properties. Suitable actuator arrays with high spatial resolution and real-time capabilities are required operating in a haptic sensor actuator system with different applications. The sensor system uses real time ultrasonic elastography whereas the tactile actuator is based on electrorheological fluids. Due to their small size the actuator array elements have to be manufactured by micro-mechanical production methods. In order to supply the actuator elements with individual high voltages a sophisticated switching and control concept have been designed. This haptic system has the potential of inducing real time substantial forces, using a compact lightweight mechanism which can be applied to numerous areas including intraoperative navigation, telemedicine, teaching, space and telecommunication.

A compact, in vivo screen of all 6-mers reveals drivers of tissue-specific expression and guides synthetic regulatory element design.

PubMed

Smith, Robin P; Riesenfeld, Samantha J; Holloway, Alisha K; Li, Qiang; Murphy, Karl K; Feliciano, Natalie M; Orecchia, Lorenzo; Oksenberg, Nir; Pollard, Katherine S; Ahituv, Nadav

2013-07-18

Large-scale annotation efforts have improved our ability to coarsely predict regulatory elements throughout vertebrate genomes. However, it is unclear how complex spatiotemporal patterns of gene expression driven by these elements emerge from the activity of short, transcription factor binding sequences. We describe a comprehensive promoter extension assay in which the regulatory potential of all 6 base-pair (bp) sequences was tested in the context of a minimal promoter. To enable this large-scale screen, we developed algorithms that use a reverse-complement aware decomposition of the de Bruijn graph to design a library of DNA oligomers incorporating every 6-bp sequence exactly once. Our library multiplexes all 4,096 unique 6-mers into 184 double-stranded 15-bp oligomers, which is sufficiently compact for in vivo testing. We injected each multiplexed construct into zebrafish embryos and scored GFP expression in 15 tissues at two developmental time points. Twenty-seven constructs produced consistent expression patterns, with the majority doing so in only one tissue. Functional sequences are enriched near biologically relevant genes, match motifs for developmental transcription factors, and are required for enhancer activity. By concatenating tissue-specific functional sequences, we generated completely synthetic enhancers for the notochord, epidermis, spinal cord, forebrain and otic lateral line, and show that short regulatory sequences do not always function modularly. This work introduces a unique in vivo catalog of short, functional regulatory sequences and demonstrates several important principles of regulatory element organization. Furthermore, we provide resources for designing compact, reverse-complement aware k-mer libraries.

Exploring Biogeochemistry and Microbial Diversity of Extant Microbialites in Mexico and Cuba

PubMed Central

Valdespino-Castillo, Patricia M.; Hu, Ping; Merino-Ibarra, Martín; López-Gómez, Luz M.; Cerqueda-García, Daniel; González-De Zayas, Roberto; Pi-Puig, Teresa; Lestayo, Julio A.; Holman, Hoi-Ying; Falcón, Luisa I.

2018-01-01

Microbialites are modern analogs of ancient microbial consortia that date as far back as the Archaean Eon. Microbialites have contributed to the geochemical history of our planet through their diverse metabolic capacities that mediate mineral precipitation. These mineral-forming microbial assemblages accumulate major ions, trace elements and biomass from their ambient aquatic environments; their role in the resulting chemical structure of these lithifications needs clarification. We studied the biogeochemistry and microbial structure of microbialites collected from diverse locations in Mexico and in a previously undescribed microbialite in Cuba. We examined their structure, chemistry and mineralogy at different scales using an array of nested methods including 16S rRNA gene high-throughput sequencing, elemental analysis, X-Ray fluorescence (XRF), X-Ray diffraction (XRD), Scanning Electron Microscopy-Energy Dispersive Spectroscopy (SEM-EDS), Fourier Transformed Infrared (FTIR) spectroscopy and Synchrotron Radiation-based Fourier Transformed Infrared (SR-FTIR) spectromicroscopy. The resulting data revealed high biological and chemical diversity among microbialites and specific microbe to chemical correlations. Regardless of the sampling site, Proteobacteria had the most significant correlations with biogeochemical parameters such as organic carbon (Corg), nitrogen and Corg:Ca ratio. Biogeochemically relevant bacterial groups (dominant phototrophs and heterotrophs) showed significant correlations with major ion composition, mineral type and transition element content, such as cadmium, cobalt, chromium, copper and nickel. Microbial-chemical relationships were discussed in reference to microbialite formation, microbial metabolic capacities and the role of transition elements as enzyme cofactors. This paper provides an analytical baseline to drive our understanding of the links between microbial diversity with the chemistry of their lithified precipitations. PMID:29666607

Exploring Biogeochemistry and Microbial Diversity of Extant Microbialites in Mexico and Cuba.

PubMed

Valdespino-Castillo, Patricia M; Hu, Ping; Merino-Ibarra, Martín; López-Gómez, Luz M; Cerqueda-García, Daniel; González-De Zayas, Roberto; Pi-Puig, Teresa; Lestayo, Julio A; Holman, Hoi-Ying; Falcón, Luisa I

2018-01-01

Microbialites are modern analogs of ancient microbial consortia that date as far back as the Archaean Eon. Microbialites have contributed to the geochemical history of our planet through their diverse metabolic capacities that mediate mineral precipitation. These mineral-forming microbial assemblages accumulate major ions, trace elements and biomass from their ambient aquatic environments; their role in the resulting chemical structure of these lithifications needs clarification. We studied the biogeochemistry and microbial structure of microbialites collected from diverse locations in Mexico and in a previously undescribed microbialite in Cuba. We examined their structure, chemistry and mineralogy at different scales using an array of nested methods including 16S rRNA gene high-throughput sequencing, elemental analysis, X-Ray fluorescence (XRF), X-Ray diffraction (XRD), Scanning Electron Microscopy-Energy Dispersive Spectroscopy (SEM-EDS), Fourier Transformed Infrared (FTIR) spectroscopy and Synchrotron Radiation-based Fourier Transformed Infrared (SR-FTIR) spectromicroscopy. The resulting data revealed high biological and chemical diversity among microbialites and specific microbe to chemical correlations. Regardless of the sampling site, Proteobacteria had the most significant correlations with biogeochemical parameters such as organic carbon (C org ), nitrogen and C org :Ca ratio. Biogeochemically relevant bacterial groups (dominant phototrophs and heterotrophs) showed significant correlations with major ion composition, mineral type and transition element content, such as cadmium, cobalt, chromium, copper and nickel. Microbial-chemical relationships were discussed in reference to microbialite formation, microbial metabolic capacities and the role of transition elements as enzyme cofactors. This paper provides an analytical baseline to drive our understanding of the links between microbial diversity with the chemistry of their lithified precipitations.

Ultraviolet germicidal irradiation and its effects on elemental distributions in mouse embryonic fibroblast cells in x-ray fluorescence microanalysis

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

Jin, Qiaoling; Vogt, Stefan; Lai, Barry

Rapidly-frozen hydrated (cryopreserved) specimens combined with cryo-scanning x-ray fluorescence microscopy provide an ideal approach for investigating elemental distributions in biological cells and tissues. However, because cryopreservation does not deactivate potentially infectious agents associated with Risk Group 2 biological materials, one must be concerned with contamination of expensive and complicated cryogenic x-ray microscopes when working with such materials. We employed ultraviolet germicidal irradiation to decontaminate previously cryopreserved cells under liquid nitrogen, and then investigated its effects on elemental distributions under both frozen hydrated and freeze dried states with x-ray fluorescence microscopy. We show that the contents and distributions of most biologicallymore » important elements remain nearly unchanged when compared with non-ultraviolet-irradiated counterparts, even after multiple cycles of ultraviolet germicidal irradiation and cryogenic x-ray imaging. This provides a potential pathway for rendering Risk Group 2 biological materials safe for handling in multiuser cryogenic x-ray microscopes without affecting the fidelity of the results.« less

Ultraviolet germicidal irradiation and its effects on elemental distributions in mouse embryonic fibroblast cells in x-ray fluorescence microanalysis

DOE PAGES

Jin, Qiaoling; Vogt, Stefan; Lai, Barry; ...

2015-02-23

Rapidly-frozen hydrated (cryopreserved) specimens combined with cryo-scanning x-ray fluorescence microscopy provide an ideal approach for investigating elemental distributions in biological cells and tissues. However, because cryopreservation does not deactivate potentially infectious agents associated with Risk Group 2 biological materials, one must be concerned with contamination of expensive and complicated cryogenic x-ray microscopes when working with such materials. We employed ultraviolet germicidal irradiation to decontaminate previously cryopreserved cells under liquid nitrogen, and then investigated its effects on elemental distributions under both frozen hydrated and freeze dried states with x-ray fluorescence microscopy. We show that the contents and distributions of most biologicallymore » important elements remain nearly unchanged when compared with non-ultraviolet-irradiated counterparts, even after multiple cycles of ultraviolet germicidal irradiation and cryogenic x-ray imaging. This provides a potential pathway for rendering Risk Group 2 biological materials safe for handling in multiuser cryogenic x-ray microscopes without affecting the fidelity of the results.« less

Simulation of CNT-AFM tip based on finite element analysis for targeted probe of the biological cell

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

Yousefi, Amin Termeh, E-mail: at.tyousefi@gmail.com; Miyake, Mikio, E-mail: miyakejaist@gmail.com; Ikeda, Shoichiro, E-mail: sho16.ikeda@gmail.com

Carbon nanotubes (CNTs) are potentially ideal tips for atomic force microscopy (AFM) due to the robust mechanical properties, nano scale diameter and also their ability to be functionalized by chemical and biological components at the tip ends. This contribution develops the idea of using CNTs as an AFM tip in computational analysis of the biological cell’s. Finite element analysis employed for each section and displacement of the nodes located in the contact area was monitored by using an output database (ODB). This reliable integration of CNT-AFM tip process provides a new class of high performance nanoprobes for single biological cellmore » analysis.« less

An attempt to understand glioma stem cell biology through centrality analysis of a protein interaction network.

PubMed

Mallik, Mrinmay Kumar

2018-02-07

Biological networks can be analyzed using "Centrality Analysis" to identify the more influential nodes and interactions in the network. This study was undertaken to create and visualize a biological network comprising of protein-protein interactions (PPIs) amongst proteins which are preferentially over-expressed in glioma cancer stem cell component (GCSC) of glioblastomas as compared to the glioma non-stem cancer cell (GNSC) component and then to analyze this network through centrality analyses (CA) in order to identify the essential proteins in this network and their interactions. In addition, this study proposes a new centrality analysis method pertaining exclusively to transcription factors (TFs) and interactions amongst them. Moreover the relevant molecular functions, biological processes and biochemical pathways amongst these proteins were sought through enrichment analysis. A protein interaction network was created using a list of proteins which have been shown to be preferentially expressed or over-expressed in GCSCs isolated from glioblastomas as compared to the GNSCs. This list comprising of 38 proteins, created using manual literature mining, was submitted to the Reactome FIViz tool, a web based application integrated into Cytoscape, an open source software platform for visualizing and analyzing molecular interaction networks and biological pathways to produce the network. This network was subjected to centrality analyses utilizing ranked lists of six centrality measures using the FIViz application and (for the first time) a dedicated centrality analysis plug-in ; CytoNCA. The interactions exclusively amongst the transcription factors were nalyzed through a newly proposed centrality analysis method called "Gene Expression Associated Degree Centrality Analysis (GEADCA)". Enrichment analysis was performed using the "network function analysis" tool on Reactome. The CA was able to identify a small set of proteins with consistently high centrality ranks that is indicative of their strong influence in the protein protein interaction network. Similarly the newly proposed GEADCA helped identify the transcription factors with high centrality values indicative of their key roles in transcriptional regulation. The enrichment studies provided a list of molecular functions, biological processes and biochemical pathways associated with the constructed network. The study shows how pathway based databases may be used to create and analyze a relevant protein interaction network in glioma cancer stem cells and identify the essential elements within it to gather insights into the molecular interactions that regulate the properties of glioma stem cells. How these insights may be utilized to help the development of future research towards formulation of new management strategies have been discussed from a theoretical standpoint. Copyright © 2017 Elsevier Ltd. All rights reserved.

Learning Systems Biology: Conceptual Considerations toward a Web-Based Learning Platform

ERIC Educational Resources Information Center

Emmert-Streib, Frank; Dehmer, Matthias; Lyardet, Fernando

2013-01-01

Within recent years, there is an increasing need to train students, from biology and beyond, in quantitative methods that are relevant to cope with data-driven biology. Systems Biology is such a field that places a particular focus on the functional aspect of biology and molecular interacting processes. This paper deals with the conceptual design…

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…

Microbial Development and Metabolic Engineering | Bioenergy | NREL

Science.gov Websites

beaker filled with a green liquid cyanobacteria culture that is bubbling. Synthetic Biology We have utilized the power of synthetic biology to uncover relevant genetic factors to predictably regulate gene operating a gas chromatograph mass spectrometer. Systems Biology Our comprehensive systems biology

Variable-Threshold Threshold Elements,

DTIC Science & Technology

A threshold element is a mathematical model of certain types of logic gates and of a biological neuron. Much work has been done on the subject of... threshold elements with fixed thresholds; this study concerns itself with elements in which the threshold may be varied, variable- threshold threshold ...elements. Physical realizations include resistor-transistor elements, in which the threshold is simply a voltage. Variation of the threshold causes the

Impact of oxidation on protein therapeutics: Conformational dynamics of intact and oxidized acid-β-glucocerebrosidase at near-physiological pH

PubMed Central

Bobst, Cedric E; Thomas, John J; Salinas, Paul A; Savickas, Philip; Kaltashov, Igor A

2010-01-01

The solution dynamics of an enzyme acid-β-glucocerebrosidase (GCase) probed at a physiologically relevant (lysosomal) pH by hydrogen/deuterium exchange mass spectrometry (HDX-MS) reveals very uneven distribution of backbone amide protection across the polypeptide chain. Highly mobile segments are observed even within the catalytic cavity alongside highly protective segments, highlighting the importance of the balance between conformational stability and flexibility for enzymatic activity. Forced oxidation of GCase that resulted in a 40–60% reduction in in vitro biological activity affects the stability of some key structural elements within the catalytic site. These changes in dynamics occur on a longer time scale that is irrelevant for catalysis, effectively ruling out loss of structure in the catalytic site as a major factor contributing to the reduction of the catalytic activity. Oxidation also leads to noticeable destabilization of conformation in remote protein segments on a much larger scale, which is likely to increase the aggregation propensity of GCase and affect its bioavailability. Therefore, it appears that oxidation exerts its negative impact on the biological activity of GCase indirectly, primarily through accelerated aggregation and impaired trafficking. PMID:20945356

A new standard model for milk yield in dairy cows based on udder physiology at the milking-session level.

PubMed

Gasqui, Patrick; Trommenschlager, Jean-Marie

2017-08-21

Milk production in dairy cow udders is a complex and dynamic physiological process that has resisted explanatory modelling thus far. The current standard model, Wood's model, is empirical in nature, represents yield in daily terms, and was published in 1967. Here, we have developed a dynamic and integrated explanatory model that describes milk yield at the scale of the milking session. Our approach allowed us to formally represent and mathematically relate biological features of known relevance while accounting for stochasticity and conditional elements in the form of explicit hypotheses, which could then be tested and validated using real-life data. Using an explanatory mathematical and biological model to explore a physiological process and pinpoint potential problems (i.e., "problem finding"), it is possible to filter out unimportant variables that can be ignored, retaining only those essential to generating the most realistic model possible. Such modelling efforts are multidisciplinary by necessity. It is also helpful downstream because model results can be compared with observed data, via parameter estimation using maximum likelihood and statistical testing using model residuals. The process in its entirety yields a coherent, robust, and thus repeatable, model.

Objective classification of ecological status in marine water bodies using ecotoxicological information and multivariate analysis.

PubMed

Beiras, Ricardo; Durán, Iria

2014-12-01

Some relevant shortcomings have been identified in the current approach for the classification of ecological status in marine water bodies, leading to delays in the fulfillment of the Water Framework Directive objectives. Natural variability makes difficult to settle fixed reference values and boundary values for the Ecological Quality Ratios (EQR) for the biological quality elements. Biological responses to environmental degradation are frequently of nonmonotonic nature, hampering the EQR approach. Community structure traits respond only once ecological damage has already been done and do not provide early warning signals. An alternative methodology for the classification of ecological status integrating chemical measurements, ecotoxicological bioassays and community structure traits (species richness and diversity), and using multivariate analyses (multidimensional scaling and cluster analysis), is proposed. This approach does not depend on the arbitrary definition of fixed reference values and EQR boundary values, and it is suitable to integrate nonlinear, sensitive signals of ecological degradation. As a disadvantage, this approach demands the inclusion of sampling sites representing the full range of ecological status in each monitoring campaign. National or international agencies in charge of coastal pollution monitoring have comprehensive data sets available to overcome this limitation.

PathText: a text mining integrator for biological pathway visualizations

PubMed Central

Kemper, Brian; Matsuzaki, Takuya; Matsuoka, Yukiko; Tsuruoka, Yoshimasa; Kitano, Hiroaki; Ananiadou, Sophia; Tsujii, Jun'ichi

2010-01-01

Motivation: Metabolic and signaling pathways are an increasingly important part of organizing knowledge in systems biology. They serve to integrate collective interpretations of facts scattered throughout literature. Biologists construct a pathway by reading a large number of articles and interpreting them as a consistent network, but most of the models constructed currently lack direct links to those articles. Biologists who want to check the original articles have to spend substantial amounts of time to collect relevant articles and identify the sections relevant to the pathway. Furthermore, with the scientific literature expanding by several thousand papers per week, keeping a model relevant requires a continuous curation effort. In this article, we present a system designed to integrate a pathway visualizer, text mining systems and annotation tools into a seamless environment. This will enable biologists to freely move between parts of a pathway and relevant sections of articles, as well as identify relevant papers from large text bases. The system, PathText, is developed by Systems Biology Institute, Okinawa Institute of Science and Technology, National Centre for Text Mining (University of Manchester) and the University of Tokyo, and is being used by groups of biologists from these locations. Contact: brian@monrovian.com. PMID:20529930

Information Theory in Biology after 18 Years

ERIC Educational Resources Information Center

Johnson, Horton A.

1970-01-01

Reviews applications of information theory to biology, concluding that they have not proved very useful. Suggests modifications and extensions to increase the biological relevance of the theory, and speculates about applications in quantifying cell proliferation, chemical homeostasis and aging. (EB)

Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy

PubMed Central

Ujváry, István; Hanuš, Lumír

2016-01-01

Abstract Cannabidiol (CBD), the main nonpsychoactive constituent of Cannabis sativa, has shown a wide range of therapeutically promising pharmacological effects either as a sole drug or in combination with other drugs in adjunctive therapy. However, the targets involved in the therapeutic effects of CBD appear to be elusive. Furthermore, scarce information is available on the biological activity of its human metabolites which, when formed in pharmacologically relevant concentration, might contribute to or even account for the observed therapeutic effects. The present overview summarizes our current knowledge on the pharmacokinetics and metabolic fate of CBD in humans, reviews studies on the biological activity of CBD metabolites either in vitro or in vivo, and discusses relevant drug–drug interactions. To facilitate further research in the area, the reported syntheses of CBD metabolites are also catalogued. PMID:28861484

Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy.

PubMed

Ujváry, István; Hanuš, Lumír

2016-01-01

Cannabidiol (CBD), the main nonpsychoactive constituent of Cannabis sativa , has shown a wide range of therapeutically promising pharmacological effects either as a sole drug or in combination with other drugs in adjunctive therapy. However, the targets involved in the therapeutic effects of CBD appear to be elusive. Furthermore, scarce information is available on the biological activity of its human metabolites which, when formed in pharmacologically relevant concentration, might contribute to or even account for the observed therapeutic effects. The present overview summarizes our current knowledge on the pharmacokinetics and metabolic fate of CBD in humans, reviews studies on the biological activity of CBD metabolites either in vitro or in vivo , and discusses relevant drug-drug interactions. To facilitate further research in the area, the reported syntheses of CBD metabolites are also catalogued.

Biology of acute lymphoblastic leukemia (ALL): clinical and therapeutic relevance.

PubMed

Graux, Carlos

2011-04-01

Acute lymphoblastic leukemia is a heterogeneous disease comprising several clinico-biological entities. Karyotyping of leukemic cells identifies recurrent chromosome rearrangements. These are usually translocations that activate genes encoding transcription factor regulating B- or T-cell differentiation. Gene expression-array confirms the prognostic relevance of ALL subgroups identified by specific chromosomal rearrangements and isolates new subgroups. Analysis of genomic copy number changes and high throughput sequencing reveal new cryptic deletions. The challenge is now to understand how these cooperative genetic lesions interact in order to have the molecular rationales needed to select new therapeutic targets and to develop and combine inhibitors with high levels of anti-leukemic specificity. The aim of this paper is to provide some data on the biology of acute lymphoblastic leukemia which are relevant in clinical practice. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ecology, Ecosystem Management and Biology Teaching. Biology and Human Welfare.

ERIC Educational Resources Information Center

Spellerberg, Ian F.; Pritchard, Alan J.

This six-chapter document (part of a series on biology and human welfare) focuses on ecology, ecosystem management, and biology teaching. Chapter 1 discusses the basic elements of ecology (considering organisms and their environment, populations, and communities and ecosystems). Chapter 2 describes several aspects of human ecology and resources…

Vision and change in introductory physics for the life sciences

NASA Astrophysics Data System (ADS)

Mochrie, S. G. J.

2016-07-01

Since 2010, our physics department has offered a re-imagined calculus-based introductory physics sequence for the life sciences. These courses include a selection of biologically and medically relevant topics that we believe are more meaningful to undergraduate premedical and biological science students than those found in a traditional course. In this paper, we highlight new aspects of the first-semester course, and present a comparison of student evaluations of this course versus a more traditional one. We also present the effect on student perception of the relevance of physics to biology and medicine after having taken this course.

Preparation and Characterization of Biofunctionalized Inorganic Substrates.

PubMed

Dugger, Jason W; Webb, Lauren J

2015-09-29

Integrating the function of biological molecules into traditional inorganic materials and substrates couples biologically relevant function to synthetic devices and generates new materials and capabilities by combining biological and inorganic functions. At this so-called "bio/abio interface," basic biological functions such as ligand binding and catalysis can be co-opted to detect analytes with exceptional sensitivity or to generate useful molecules with chiral specificity under entirely benign reaction conditions. Proteins function in dynamic, complex, and crowded environments (the living cell) and are therefore appropriate for integrating into multistep, multiscale, multimaterial devices such as integrated circuits and heterogeneous catalysts. However, the goal of reproducing the highly specific activities of biomolecules in the perturbed chemical and electrostatic environment at an inorganic interface while maintaining their native conformations is challenging to achieve. Moreover, characterizing protein structure and function at a surface is often difficult, particularly if one wishes to compare the activity of the protein to that of the dilute, aqueous solution phase. Our laboratory has developed a general strategy to address this challenge by taking advantage of the structural and chemical properties of alkanethiol self-assembled monolayers (SAMs) on gold surfaces that are functionalized with covalently tethered peptides. These surface-bound peptides then act as the chemical recognition element for a target protein, generating a biomimetic surface in which protein orientation, structure, density, and function are controlled and variable. Herein we discuss current research and future directions related to generating a chemically tunable biofunctionalization strategy that has potential to successfully incorporate the highly specialized functions of proteins onto inorganic substrates.

An inventory and evaluation of biological investigations that relate to stream-water quality in the upper Illinois River basin of Illinois, Indiana, and Wisconsin

USGS Publications Warehouse

Steffeck, D.W.; Striegl, Robert G.

1989-01-01

Results of studies of the aquatic biology of the upper Illinois River basin provide a historical data source from which inferences can be made about changes in the quality of water in the main stem river and its tributaries. The results of biological investigations that have been conducted throughout the basin since 1900 are summarized and their relevance to stream-water-quality assessment is described, particularly their relevance to the upper Illinois River basin pilot project for the National Water Quality Assessment program. Four general categories of biological investigations were identified: Populations and community structure, chemical concentrations in tissue, organism health, and toxicity measurements. Biological investigations were identified by their location in the basin and by their relevance to each general investigation category. The most abundant literature was in the populations and community structure category. Tissue data were limited to polychlorinated biphenyls, organochlorine pesticides, dioxin, and several metals. The most cited measure of organism health was a condition factor for fish that associates body length with weight or body depth. Toxicity measurements included bioassays and the Ames Tests. The bioassays included several testing methods and test organism. (USGS)

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.

biologically relevant effects of dipentyl phthalate

EPA Pesticide Factsheets

metadata sheet, data sheet for each table and figure in the published manuscriptThis dataset is associated with the following publication:Gray , E., J. Furr , K. Tatum-Gibbs, C. Lambright , H. Sampson, B. Hannas, V. Wilson , A. Hotchkiss , and P. Foster. Establishing the Biological Relevance of Dipentyl Phthalate Reductions in Fetal Rat Testosterone Production and Plasma and Testis Testosterone Levels. TOXICOLOGICAL SCIENCES. Society of Toxicology, 149(1): 178-91, (2016).

Insights into Igneous Geochemistry from Trace Element Partitioning

NASA Technical Reports Server (NTRS)

Jones, J. H.; Hanson, B. Z.

2001-01-01

Partitioning of trivalent elements into olivine are used to explore basic issues relevant to igneous geochemistry, such as Henry's law. Additional information is contained in the original extended abstract.

Biology Curriculum Reform in Venezuela.

ERIC Educational Resources Information Center

Rondon, Leonor Mariasole

2001-01-01

Describes science in the Venezuelan school system which reflects on the process of development followed to design and validate the Biology Study Programs (BSP) with the emphasis on the relevance of curricular changes proposed in biological science for secondary education. (Contains 19 references.) (ASK)

An economic cost analysis of emergency department key performance indicators in Ireland.

PubMed

Gannon, Brenda; Jones, Cheryl; McCabe, Aileen; O'Sullivan, Ronan; Wakai, Abel

2017-06-01

High quality data is fundamental to using key performance indicators (KPIs) for performance monitoring. However, the resources required to collect high quality data are often significant and should usually be targeted at high priority areas. As part of a study of 11 emergency department (ED) KPIs in Ireland, the primary objective of this study was to estimate the relative cost of collecting the additional minimum data set (MDS) elements for those 11 KPIs. An economic cost analysis focused on 12 EDs in the Republic of Ireland. The resource use data were obtained using two separate focus group interviews. The number of available MDS elements was obtained from a sample of 100 patient records per KPI per participating ED. Unit costs for all resource use were taken at the midpoint of the relevant staff salary scales. An ED would need to spend an estimated additional &OV0556;3561 per month on average to capture all the MDS elements relevant to the 11 KPIs investigated. The additional cost ranges from 14.8 to 39.2%; this range is 13.9-32.3% for small EDs, whereas the range for medium EDs is 11.7-40%. Regional EDs have a higher additional estimated cost to capture all the relevant MDS elements (&OV0556;3907), compared with urban EDs (&OV0556;3353). The additional cost of data collection, contingent on that already collected, required to capture all the relevant MDS elements for the KPIs examined, ranges from 14.8 to 39.2% per KPI, with variation identified between regional and urban hospitals.

Biological cell classification by multiangle light scattering

DOEpatents

Salzman, G.C.; Crowell, J.M.; Mullaney, P.F.

1975-06-03

The specification is directed to an apparatus and method for detecting light scattering from a biological cell. Light, preferably from a coherent source of radiation, intercepts an individual biological cell in a stream of cells passing through the beam. Light scattered from the cell is detected at a selected number of angles between 0 and 90/sup 0/ to the longitudinal axis of the beam with a circular array of light responsive elements which produce signals representative of the intensity of light incident thereon. Signals from the elements are processed to determine the light-scattering pattern of the cell and therefrom its identity.

Geochemical and Isotopic Estimates of Eolian Dust in Soils of the San Juan Mountains, USA.

NASA Astrophysics Data System (ADS)

Lawrence, C. R.; Neff, J. C.; Farmer, L.; Painter, T. H.; Landry, C.

2007-12-01

Eolian dust deposition in the San Juan Mountain Range in southern Colorado has increased 5-7 fold in the past two centuries. This dust deposition contributes an exogenous supply of biologically relevant elements such as Ca, K, Mg, and P to these alpine ecosystems in the form of fine textured mineral particulates. The deposition of eolian dust may be an underestimated factor of soil formation and soil chemistry in these alpine settings. The importance of eolian dust relative to the weathering of local bedrock likely varies across bedrock types. The San Juan Range is geologically diverse with distinct regions of Meso-proterozic crystalline granites in the Weminuche Wilderness, Mesozoic sedimentary layers near Molas Pass in the San Juan National Forest, and Tertiary volcanic geology found on Red Mountain Pass in the Uncompahgre National Forest. Principle component analysis of element chemistry shows that bedrock and soils from these sites cluster by geology. In addition, these groups are chemically distinct from eolian dust collected from snow in the San Juan Range. Several elements seem to drive the difference of dust from soils and bedrock including Ca, Sr, Cu and Cd. The purpose of this research was to estimate the relative contribution of eolian dust to alpine soil element pools in the San Juan Mountains across a range of local geologic parent material. A calculation of element mass- balance shows that Cu and Cd are enriched in the surface soils of both volcanic and sedimentary soils relative to concentrations in local bedrock. However, Ca is enriched only in volcanic soils. These observations support the notion that eolian dust contributes to soil formation and that the relative contribution of dust across the landscape varies with geology. In addition to element mass-balance estimates we utilize Sr and Nd isotope measurements of soil, bedrock, and dust to further constrain the importance of eolian dust to these alpine soils.

Elemental Education.

ERIC Educational Resources Information Center

Daniel, Esther Gnanamalar Sarojini; Saat, Rohaida Mohd.

2001-01-01

Introduces a learning module integrating three disciplines--physics, chemistry, and biology--and based on four elements: carbon, oxygen, hydrogen, and silicon. Includes atomic model and silicon-based life activities. (YDS)

IQ Predicts Biological Motion Perception in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Rutherford, M. D.; Troje, Nikolaus F.

2012-01-01

Biological motion is easily perceived by neurotypical observers when encoded in point-light displays. Some but not all relevant research shows significant deficits in biological motion perception among those with ASD, especially with respect to emotional displays. We tested adults with and without ASD on the perception of masked biological motion…

Teaching Biology through Statistics: Application of Statistical Methods in Genetics and Zoology Courses

ERIC Educational Resources Information Center

Colon-Berlingeri, Migdalisel; Burrowes, Patricia A.

2011-01-01

Incorporation of mathematics into biology curricula is critical to underscore for undergraduate students the relevance of mathematics to most fields of biology and the usefulness of developing quantitative process skills demanded in modern biology. At our institution, we have made significant changes to better integrate mathematics into the…

Moving beyond the van Krevelen Diagram: A New Stoichiometric Approach for Compound Classification in Organisms

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

Rivas-Ubach, Albert; Liu, Yina; Bianchi, Thomas S.

van Krevelen diagrams (O:C vs H:C ratios of elemental formulas) have been widely used in studies to obtain an estimation of the main compound categories present in environmental samples. However, the limits defining a specific compound category based solely on O:C and H:C ratios of elemental formulas have never been accurately listed or proposed to classify metabolites in biological samples. Furthermore, while O:C vs. H:C ratios of elemental formulas can provide an overview of the compound categories, such classification is inefficient because of the large overlap among different compound categories along both axes. We propose a more accurate compound classificationmore » for biological samples analyzed by high-resolution mass spectrometry-based on an assessment of the C:H:O:N:P stoichiometric ratios of over 130,000 elemental formulas of compounds classified in 6 main categories: lipids, peptides, amino-sugars, carbohydrates, nucleotides and phytochemical compounds (oxy-aromatic compounds). Our multidimensional stoichiometric compound classification (MSCC) constraints showed a highly accurate categorization of elemental formulas to the main compound categories in biological samples with over 98% of accuracy representing a substantial improvement over any classification based on the classic van Krevelen diagram. This method represents a significant step forward in environmental research, especially ecological stoichiometry and eco-metabolomics studies, by providing a novel and robust tool to further our understanding the ecosystem structure and function through the chemical characterization of different biological samples.« less

Focus issue: series on computational and systems biology.

PubMed

Gough, Nancy R

2011-09-06

The application of computational biology and systems biology is yielding quantitative insight into cellular regulatory phenomena. For the month of September, Science Signaling highlights research featuring computational approaches to understanding cell signaling and investigation of signaling networks, a series of Teaching Resources from a course in systems biology, and various other articles and resources relevant to the application of computational biology and systems biology to the study of signal transduction.

Water-quality, bed-sediment, and biological data (October 1993 through September 1994) and statistical summaries of data for streams in the Upper Clark Fork basin, Montana

USGS Publications Warehouse

Lambing, J.H.; Hornberger, Michelle I.; Axtmann, E.V.; Dodge, K.A.

1995-01-01

Water, bed sediment, and biota were sampled in streams from Butte to below Missoula as part of a program to characterize aquatic resources in the upper Clark Fork basin of western Montana. Water- quality data were obtained periodically at 16 stations during October 1993 through September 1994 (water year 1994); daily suspended-sediment data were obtained at six of these stations. Bed-sediment and biological data were obtained at 11 stations in August 1994. Sampling stations were located on the Clark Fork and major tributaries. The primary constituents analyzed were trace elements associated with mine tailings from historical mining and smelting activities. Water-quality data include concentrations of major ions, trace elements, and suspended sediment in samples collected periodically during water year 1994. Daily values of streamflow, suspended-sediment concentration, and suspended- sediment discharge are given for six stations. Bed- sediment data include trace-element concentrations in the fine and bulk fractions. Biological data include trace-element concentrations in whole-body tissue of aquatic benthic insects. Quality-assurance data are reported for analytical results of water, bed sediment, and biota. Statistical summaries of bed sediment, and biological data are provided for the period of record at each station since 1985.

ISSUES IN SIMULATING ELEMENTAL MERCURY AIR/WATER EXCHANGE AND AQUEOUS MONOMETHYLMERCURY SPECIATION

EPA Science Inventory

This presentation focuses on two areas relevant to assessing the global fate and bioavailability of mercury: elemental mercury air/water exchange and aqueous environmental monomethylmercury speciation.

Evaluation of biological hydrogen sulfide oxidation coupled with two-stage upflow filtration for groundwater treatment.

PubMed

Levine, Audrey D; Raymer, Blake J; Jahn, Johna

2004-01-01

Hydrogen sulfide in groundwater can be oxidized by aerobic bacteria to form elemental sulfur and biomass. While this treatment approach is effective for conversion of hydrogen sulfide, it is important to have adequate control of the biomass exiting the biological treatment system to prevent release of elemental sulfur into the distribution system. Pilot scale tests were conducted on a Florida groundwater to evaluate the use of two-stage upflow filtration downstream of biological sulfur oxidation. The combined biological and filtration process was capable of excellent removal of hydrogen sulfide and associated turbidity. Additional benefits of this treatment approach include elimination of odor generation, reduction of chlorine demand, and improved stability of the finished water.

Severe impingement of lumbar disc replacements increases the functional biological activity of polyethylene wear debris.

PubMed

Baxter, Ryan M; Macdonald, Daniel W; Kurtz, Steven M; Steinbeck, Marla J

2013-06-05

Wear, oxidation, and particularly rim impingement damage of ultra-high molecular weight polyethylene total disc replacement components have been observed following surgical revision. However, neither in vitro testing nor retrieval-based evidence has shown the effect(s) of impingement on the characteristics of polyethylene wear debris. Thus, we sought to determine (1) differences in polyethylene particle size, shape, number, or biological activity that correspond to mild or severe rim impingement and (2) in an analysis of all total disc replacements, regardless of impingement classification, whether there are correlations between the extent of regional damage and the characteristics of polyethylene wear debris. The extent of dome and rim damage was characterized for eleven retrieved polyethylene cores obtained at revision surgery after an average duration of implantation of 9.7 years (range, 4.6 to 16.1 years). Polyethylene wear debris was isolated from periprosthetic tissues with use of nitric acid and was imaged with use of environmental scanning electron microscopy. Subsequently, particle size, shape, number, biological activity, and chronic inflammation scores were determined. Grouping of particles by size ranges that represented high biological relevance (<0.1 to 1-μm particles), intermediate biological relevance (1 to 10-μm particles), and low biological relevance (>10-μm particles) revealed an increased volume fraction of particles in the <0.1 to 1-μm and 1 to 10-μm size ranges in the mild-impingement cohort as compared with the severe-impingement cohort. The increased volume fractions resulted in a higher specific biological activity per unit particle volume in the mild-impingement cohort than in the severe-impingement cohort. However, functional biological activity, which is normalized by particle volume (mm3/g of tissue), was significantly higher in the severe-impingement cohort. This increase was due to a larger volume of particles in all three size ranges. In both cohorts, the functional biological activity correlated with the chronic inflammatory response, and the extent of rim penetration positively correlated with increasing particle size, number, and functional biological activity. The results of this study suggest that severe rim impingement increases the production of biologically relevant particles from motion-preserving lumbar total disc replacement components. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Severe Impingement of Lumbar Disc Replacements Increases the Functional Biological Activity of Polyethylene Wear Debris

PubMed Central

Baxter, Ryan M.; MacDonald, Daniel W.; Kurtz, Steven M.; Steinbeck, Marla J.

2013-01-01

Background: Wear, oxidation, and particularly rim impingement damage of ultra-high molecular weight polyethylene total disc replacement components have been observed following surgical revision. However, neither in vitro testing nor retrieval-based evidence has shown the effect(s) of impingement on the characteristics of polyethylene wear debris. Thus, we sought to determine (1) differences in polyethylene particle size, shape, number, or biological activity that correspond to mild or severe rim impingement and (2) in an analysis of all total disc replacements, regardless of impingement classification, whether there are correlations between the extent of regional damage and the characteristics of polyethylene wear debris. Methods: The extent of dome and rim damage was characterized for eleven retrieved polyethylene cores obtained at revision surgery after an average duration of implantation of 9.7 years (range, 4.6 to 16.1 years). Polyethylene wear debris was isolated from periprosthetic tissues with use of nitric acid and was imaged with use of environmental scanning electron microscopy. Subsequently, particle size, shape, number, biological activity, and chronic inflammation scores were determined. Results: Grouping of particles by size ranges that represented high biological relevance (<0.1 to 1-μm particles), intermediate biological relevance (1 to 10-μm particles), and low biological relevance (>10-μm particles) revealed an increased volume fraction of particles in the <0.1 to 1-μm and 1 to 10-μm size ranges in the mild-impingement cohort as compared with the severe-impingement cohort. The increased volume fractions resulted in a higher specific biological activity per unit particle volume in the mild-impingement cohort than in the severe-impingement cohort. However, functional biological activity, which is normalized by particle volume (mm3/g of tissue), was significantly higher in the severe-impingement cohort. This increase was due to a larger volume of particles in all three size ranges. In both cohorts, the functional biological activity correlated with the chronic inflammatory response, and the extent of rim penetration positively correlated with increasing particle size, number, and functional biological activity. Conclusions: The results of this study suggest that severe rim impingement increases the production of biologically relevant particles from motion-preserving lumbar total disc replacement components. Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID:23780545

Symposium: The Role of Biological Sciences in the Optometric Curriculum.

ERIC Educational Resources Information Center

And Others; Rapp, Jerry

1980-01-01

Papers from a symposium probing some of the curricular elements of the program in biological sciences at a school or college of optometry are provided. The overall program sequence in the biological sciences, microbiology, pharmacology, and the curriculum in the biological sciences from a clinical perspective are discussed. (Author/MLW)

Trace element bias in the use of CO2 vents as analogues for low pH environments: Implications for contamination levels in acidified oceans

NASA Astrophysics Data System (ADS)

Vizzini, S.; Di Leonardo, R.; Costa, V.; Tramati, C. D.; Luzzu, F.; Mazzola, A.

2013-12-01

Research into the effects of ocean acidification on marine ecosystems has increasingly focused on natural CO2 vents, although their intrinsic environmental complexity means observations from these areas may not relate exclusively to pH gradients. In order to assess trace element levels and distribution in the Levante Bay (Vulcano Island, NE Sicily, Italy) and its suitability for studying biological effects of pH decline, Ba, Fe and trace elements (As, Cd, Co, Cr, Cu, Hg, Mn, Mo, Ni, Pb, V and Zn) in sediment were analysed from 7 transects. Where present, Cymodocea nodosa leaves and epiphytes were also analysed. At the spatial scale of the bay, trace element concentrations in sediments and biota showed wide variability, possibly related to both input from fluid emissions and seawater physico-chemical variables (i.e. pH and Eh), which may considerably affect the solubility and bioavailability of potentially harmful trace elements. According to two pollution indices (MSPI: Marine Sediment Pollution Index and SQG-Q: Sediment Quality Guideline Quotient), the bay can be considered to be affected by low contamination with moderate potential for adverse biological effects, especially in the area between about 150 and 350 m from the primary vent, where localized detrimental effects on biota may occur. Generally, biological samples showed concentrations that were comparable with the lower values of seagrass ranges. The overall results of this study support the complex spatial dynamics of trace elements in the CO2 vent studied, which are constrained by both direct input from the vent and/or biogeochemical processes affecting element precipitation at the sediment-seawater interface. Consequently, great caution should be used when relating biological changes along pH gradients to the unifactorial effect of pH only, as interactions with concurrent, multiple stressors, including trace element enrichments, may occur. This finding has implications for the use of CO2 vents as analogues in ocean acidification research. They should be considered more appropriately as analogues for low pH environments with non-negligible trace element contamination which, in a scenario of continuous increase in anthropogenic pollution, may be very common.

Time to tenure in Spanish universities: an event history analysis.

PubMed

Sanz-Menéndez, Luis; Cruz-Castro, Laura; Alva, Kenedy

2013-01-01

Understanding how institutional incentives and mechanisms for assigning recognition shape access to a permanent job is important. This study, based on data from questionnaire survey responses and publications of 1,257 university science, biomedical and engineering faculty in Spain, attempts to understand the timing of getting a permanent position and the relevant factors that account for this transition, in the context of dilemmas between mobility and permanence faced by organizations. Using event history analysis, the paper looks at the time to promotion and the effects of some relevant covariates associated to academic performance, social embeddedness and mobility. We find that research productivity contributes to career acceleration, but that other variables are also significantly associated to a faster transition. Factors associated to the social elements of academic life also play a role in reducing the time from PhD graduation to tenure. However, mobility significantly increases the duration of the non-tenure stage. In contrast with previous findings, the role of sex is minor. The variations in the length of time to promotion across different scientific domains is confirmed, with faster career advancement for those in the Engineering and Technological Sciences compared with academics in the Biological and Biomedical Sciences. Results show clear effects of seniority, and rewards to loyalty, in addition to some measurements of performance and quality of the university granting the PhD, as key elements speeding up career advancement. Findings suggest the existence of a system based on granting early permanent jobs to those that combine social embeddedness and team integration with some good credentials regarding past and potential future performance, rather than high levels of mobility.

Time to Tenure in Spanish Universities: An Event History Analysis

PubMed Central

Sanz-Menéndez, Luis; Cruz-Castro, Laura; Alva, Kenedy

2013-01-01

Understanding how institutional incentives and mechanisms for assigning recognition shape access to a permanent job is important. This study, based on data from questionnaire survey responses and publications of 1,257 university science, biomedical and engineering faculty in Spain, attempts to understand the timing of getting a permanent position and the relevant factors that account for this transition, in the context of dilemmas between mobility and permanence faced by organizations. Using event history analysis, the paper looks at the time to promotion and the effects of some relevant covariates associated to academic performance, social embeddedness and mobility. We find that research productivity contributes to career acceleration, but that other variables are also significantly associated to a faster transition. Factors associated to the social elements of academic life also play a role in reducing the time from PhD graduation to tenure. However, mobility significantly increases the duration of the non-tenure stage. In contrast with previous findings, the role of sex is minor. The variations in the length of time to promotion across different scientific domains is confirmed, with faster career advancement for those in the Engineering and Technological Sciences compared with academics in the Biological and Biomedical Sciences. Results show clear effects of seniority, and rewards to loyalty, in addition to some measurements of performance and quality of the university granting the PhD, as key elements speeding up career advancement. Findings suggest the existence of a system based on granting early permanent jobs to those that combine social embeddedness and team integration with some good credentials regarding past and potential future performance, rather than high levels of mobility. PMID:24116199

Discriminative prediction of mammalian enhancers from DNA sequence

PubMed Central

Lee, Dongwon; Karchin, Rachel; Beer, Michael A.

2011-01-01

Accurately predicting regulatory sequences and enhancers in entire genomes is an important but difficult problem, especially in large vertebrate genomes. With the advent of ChIP-seq technology, experimental detection of genome-wide EP300/CREBBP bound regions provides a powerful platform to develop predictive tools for regulatory sequences and to study their sequence properties. Here, we develop a support vector machine (SVM) framework which can accurately identify EP300-bound enhancers using only genomic sequence and an unbiased set of general sequence features. Moreover, we find that the predictive sequence features identified by the SVM classifier reveal biologically relevant sequence elements enriched in the enhancers, but we also identify other features that are significantly depleted in enhancers. The predictive sequence features are evolutionarily conserved and spatially clustered, providing further support of their functional significance. Although our SVM is trained on experimental data, we also predict novel enhancers and show that these putative enhancers are significantly enriched in both ChIP-seq signal and DNase I hypersensitivity signal in the mouse brain and are located near relevant genes. Finally, we present results of comparisons between other EP300/CREBBP data sets using our SVM and uncover sequence elements enriched and/or depleted in the different classes of enhancers. Many of these sequence features play a role in specifying tissue-specific or developmental-stage-specific enhancer activity, but our results indicate that some features operate in a general or tissue-independent manner. In addition to providing a high confidence list of enhancer targets for subsequent experimental investigation, these results contribute to our understanding of the general sequence structure of vertebrate enhancers. PMID:21875935

[Network structures in biological systems].

PubMed

Oleskin, A V

2013-01-01

Network structures (networks) that have been extensively studied in the humanities are characterized by cohesion, a lack of a central control unit, and predominantly fractal properties. They are contrasted with structures that contain a single centre (hierarchies) as well as with those whose elements predominantly compete with one another (market-type structures). As far as biological systems are concerned, their network structures can be subdivided into a number of types involving different organizational mechanisms. Network organization is characteristic of various structural levels of biological systems ranging from single cells to integrated societies. These networks can be classified into two main subgroups: (i) flat (leaderless) network structures typical of systems that are composed of uniform elements and represent modular organisms or at least possess manifest integral properties and (ii) three-dimensional, partly hierarchical structures characterized by significant individual and/or intergroup (intercaste) differences between their elements. All network structures include an element that performs structural, protective, and communication-promoting functions. By analogy to cell structures, this element is denoted as the matrix of a network structure. The matrix includes a material and an immaterial component. The material component comprises various structures that belong to the whole structure and not to any of its elements per se. The immaterial (ideal) component of the matrix includes social norms and rules regulating network elements' behavior. These behavioral rules can be described in terms of algorithms. Algorithmization enables modeling the behavior of various network structures, particularly of neuron networks and their artificial analogs.

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…

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.

Relevance in the science classroom: A multidimensional analysis

NASA Astrophysics Data System (ADS)

Hartwell, Matthew F.

While perceived relevance is considered a fundamental component of adaptive learning, the experience of relevance and its conceptual definition have not been well described. The mixed-methods research presented in this dissertation aimed to clarify the conceptual meaning of relevance by focusing on its phenomenological experience from the students' perspective. Following a critical literature review, I propose an identity-based model of perceived relevance that includes three components: a contextual target, an identity target, and a connection type, or lens. An empirical investigation of this model that consisted of two general phases was implemented in four 9th grade-biology classrooms. Participants in Phase 1 (N = 118) completed a series of four open-ended writing activities focused on eliciting perceived personal connections to academic content. Exploratory qualitative content analysis of a 25% random sample of the student responses was used to identify the main meaning-units of the proposed model as well as different dimensions of student relevance perceptions. These meaning-units and dimensions provided the basis for the construction of a conceptual mapping sentence capturing students' perceived relevance, which was then applied in a confirmatory analysis to all other student responses. Participants in Phase 2 (N = 139) completed a closed survey designed based on the mapping sentence to assess their perceived relevance of a biology unit. The survey also included scales assessing other domain-level motivational processes. Exploratory factor analysis and non-metric multidimensional scaling indicated a coherent conceptual structure, which included a primary interpretive relevance dimension. Comparison of the conceptual structure across various groups (randomly-split sample, gender, academic level, domain-general motivational profiles) provided support for its ubiquity and insight into variation in the experience of perceived relevance among students of different groups. The findings combine to support a multidimensional perspective of relevance in the 9th grade biology classroom; offering researchers a useful model for future investigation and educators with insights into the students' classroom experience.

Recent developments on ultrasound-assisted one-pot multicomponent synthesis of biologically relevant heterocycles.

PubMed

Banerjee, Bubun

2017-03-01

Heterocycles are the backbone of organic compounds. Specially, N- &O-containing heterocycles represent privileged structural subunits well distributed in naturally occurring compounds with immense biological activities. Multicomponent reactions (MCRs) are becoming valuable tool for synthesizing structurally diverse molecular entities. On the other hand, the last decade has seen a tremendous outburst in modifying chemical processes to make them sustainable for the betterment of our environment. The application of ultrasound in organic synthesis is fulfilling some of the goals of 'green and sustainable chemistry' as it has some advantages over the traditional thermal methods in terms of reaction rates, yields, purity of the products, product selectivity, etc. Therefore the synthesis of biologically relevant heterocycles using one-pot multi-component technique coupled with the application of ultrasound is one of the thrusting areas in the 21st Century among the organic chemists. The present review deals with the "up to date" developments on ultrasound assisted one-pot multi-component synthesis of biologically relevant heterocycles reported so far. Copyright © 2016 Elsevier B.V. All rights reserved.

Stabilization of RNA hairpins using non-nucleotide linkers and circularization.

PubMed

Kiliszek, Agnieszka; Blaszczyk, Leszek; Kierzek, Ryszard; Rypniewski, Wojciech

2017-06-02

An RNA hairpin is an essential structural element of RNA. Hairpins play crucial roles in gene expression and intermolecular recognition but are also involved in the pathogenesis of some congenital diseases. Structural studies of the hairpin motifs are impeded by their thermodynamic instability, as they tend to unfold to form duplexes, especially at high concentrations required for crystallography or nuclear magnetic resonance spectroscopy. We have elaborated techniques to stabilize the RNA hairpins by linking the free ends of the RNA strand at the base of the hairpin stem. One method involves stilbene diether or hexaethylene glycol linkers and circularization by T4 RNA ligase. Another method uses click chemistry to stitch the RNA ends with a triazole linker. Both techniques are efficient and easy to perform. They should be useful in making stable, biologically relevant RNA constructs for structural studies. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Zn2+ -Ion Sensing by Fluorescent Schiff Base Calix[4]arene Macrocycles.

PubMed

Ullmann, Steve; Schnorr, René; Handke, Marcel; Laube, Christian; Abel, Bernd; Matysik, Jörg; Findeisen, Matthias; Rüger, Robert; Heine, Thomas; Kersting, Berthold

2017-03-17

A macrocyclic ligand (H 2 L) containing two o,o'-bis(iminomethyl)phenol and two calix[4]arene head units has been synthesized and its coordination chemistry towards divalent Ni and Zn investigated. The new macrocycle forms complexes of composition [ML] (M=Zn, M=Ni) and [ZnL(py) 2 ], which were characterized by elemental analysis; IR, UV/Vis, and NMR spectroscopy; electrospray ionization mass spectrometry (ESI-MS); and X-ray crystallography (for [ZnL(py) 2 ] and [NiL]). H 2 L allows the sensitive optical detection of Zn 2+ among a series of biologically relevant metal ions by a dual fluorescence enhancement/quenching effect in solution. The fluorescence intensity of the macrocycle increases by a factor of ten in the presence of Zn 2+ with a detection limit in the lower nanomolar region. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Integrative analysis of 111 reference human epigenomes

PubMed Central

Kundaje, Anshul; Meuleman, Wouter; Ernst, Jason; Bilenky, Misha; Yen, Angela; Kheradpour, Pouya; Zhang, Zhizhuo; Heravi-Moussavi, Alireza; Liu, Yaping; Amin, Viren; Ziller, Michael J; Whitaker, John W; Schultz, Matthew D; Sandstrom, Richard S; Eaton, Matthew L; Wu, Yi-Chieh; Wang, Jianrong; Ward, Lucas D; Sarkar, Abhishek; Quon, Gerald; Pfenning, Andreas; Wang, Xinchen; Claussnitzer, Melina; Coarfa, Cristian; Harris, R Alan; Shoresh, Noam; Epstein, Charles B; Gjoneska, Elizabeta; Leung, Danny; Xie, Wei; Hawkins, R David; Lister, Ryan; Hong, Chibo; Gascard, Philippe; Mungall, Andrew J; Moore, Richard; Chuah, Eric; Tam, Angela; Canfield, Theresa K; Hansen, R Scott; Kaul, Rajinder; Sabo, Peter J; Bansal, Mukul S; Carles, Annaick; Dixon, Jesse R; Farh, Kai-How; Feizi, Soheil; Karlic, Rosa; Kim, Ah-Ram; Kulkarni, Ashwinikumar; Li, Daofeng; Lowdon, Rebecca; Mercer, Tim R; Neph, Shane J; Onuchic, Vitor; Polak, Paz; Rajagopal, Nisha; Ray, Pradipta; Sallari, Richard C; Siebenthall, Kyle T; Sinnott-Armstrong, Nicholas; Stevens, Michael; Thurman, Robert E; Wu, Jie; Zhang, Bo; Zhou, Xin; Beaudet, Arthur E; Boyer, Laurie A; De Jager, Philip; Farnham, Peggy J; Fisher, Susan J; Haussler, David; Jones, Steven; Li, Wei; Marra, Marco; McManus, Michael T; Sunyaev, Shamil; Thomson, James A; Tlsty, Thea D; Tsai, Li-Huei; Wang, Wei; Waterland, Robert A; Zhang, Michael; Chadwick, Lisa H; Bernstein, Bradley E; Costello, Joseph F; Ecker, Joseph R; Hirst, Martin; Meissner, Alexander; Milosavljevic, Aleksandar; Ren, Bing; Stamatoyannopoulos, John A; Wang, Ting; Kellis, Manolis

2015-01-01

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but a similar reference has lacked for epigenomic studies. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection to-date of human epigenomes for primary cells and tissues. Here, we describe the integrative analysis of 111 reference human epigenomes generated as part of the program, profiled for histone modification patterns, DNA accessibility, DNA methylation, and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically-relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation, and human disease. PMID:25693563

Intraoperative irradiation: precision medicine for quality cancer control promotion.

PubMed

Calvo, Felipe A

2017-02-02

Intraoperative irradiation was implemented 4 decades ago, pioneering the efforts to improve precision in local cancer therapy by combining real-time surgical exploration/resection with high single dose radiotherapy (Gunderson et al., Intraoperative irradiation: techniques and results, 2011). Clinical and technical developments have led to very precise radiation dose deposit. The ability to deliver a very precise dose of radiation is an essential element of contemporary multidisciplinary individualized oncology.This issue of Radiation Oncology contains a collection of expert review articles and updates with relevant data regarding intraoperative radiotherapy. Technology, physics, biology of single dose and clinical results in a variety of cancer sites and histologies are described and analyzed. The state of the art for advanced cancer care through medical innovation opens a significant opportunity for individualize cancer management across a broad spectrum of clinical practice. The advantage for tailoring diagnostic and treatment decisions in an individualized fashion will translate into precise medical treatment.

High transconductance organic electrochemical transistors

NASA Astrophysics Data System (ADS)

Khodagholy, Dion; Rivnay, Jonathan; Sessolo, Michele; Gurfinkel, Moshe; Leleux, Pierre; Jimison, Leslie H.; Stavrinidou, Eleni; Herve, Thierry; Sanaur, Sébastien; Owens, Róisín M.; Malliaras, George G.

2013-07-01

The development of transistors with high gain is essential for applications ranging from switching elements and drivers to transducers for chemical and biological sensing. Organic transistors have become well-established based on their distinct advantages, including ease of fabrication, synthetic freedom for chemical functionalization, and the ability to take on unique form factors. These devices, however, are largely viewed as belonging to the low-end of the performance spectrum. Here we present organic electrochemical transistors with a transconductance in the mS range, outperforming transistors from both traditional and emerging semiconductors. The transconductance of these devices remains fairly constant from DC up to a frequency of the order of 1 kHz, a value determined by the process of ion transport between the electrolyte and the channel. These devices, which continue to work even after being crumpled, are predicted to be highly relevant as transducers in biosensing applications.

Biomimetic Delivery with Micro- and Nanoparticles

PubMed Central

Balmert, Stephen C.; Little, Steven R.

2013-01-01

The nascent field of biomimetic delivery with micro- and nanoparticles (MNP) has advanced considerably in recent years. Drawing inspiration from the ways that cells communicate in the body, several different modes of “delivery” (i.e. temporospatial presentation of biological signals) have been investigated in a number of therapeutic contexts. In particular, this review focuses on (1) controlled release formulations that deliver natural soluble factors with physiologically relevant temporal context, (2) presentation of surface-bound ligands to cells, with spatial organization of ligands ranging from isotropic to dynamically anisotropic, and (3) physical properties of particles, including size, shape and mechanical stiffness, which mimic those of natural cells. Importantly, the context provided by multimodal, or multifactor delivery represents a key element of most biomimetic MNP systems, a concept illustrated by an analogy to human interpersonal communication. Regulatory implications of increasingly sophisticated and “cell-like” biomimetic MNP systems are also discussed. PMID:22528985

Genetics against race: Science, politics and affirmative action in Brazil

PubMed Central

Kent, Michael; Wade, Peter

2015-01-01

This article analyses interrelations between genetic ancestry research, political conflict and social identity. It focuses on the debate on race-based affirmative action policies, which have been implemented in Brazil since the turn of the century. Genetic evidence of high levels of admixture in the Brazilian population has become a key element of arguments that question the validity of the category of race for the development of public policies. In response, members of Brazil’s black movement have dismissed the relevance of genetics by arguing, first, that in Brazil race functions as a social – rather than a biological – category, and, second, that racial classification and discrimination in this country are based on appearance, rather than on genotype. This article highlights the importance of power relations and political interests in shaping public engagements with genetic research and their social consequences. PMID:27479998

Epigenetic processes in flowering plant reproduction.

PubMed

Wang, Guifeng; Köhler, Claudia

2017-02-01

Seeds provide up to 70% of the energy intake of the human population, emphasizing the relevance of understanding the genetic and epigenetic mechanisms controlling seed formation. In flowering plants, seeds are the product of a double fertilization event, leading to the formation of the embryo and the endosperm surrounded by maternal tissues. Analogous to mammals, plants undergo extensive epigenetic reprogramming during both gamete formation and early seed development, a process that is supposed to be required to enforce silencing of transposable elements and thus to maintain genome stability. Global changes of DNA methylation, histone modifications, and small RNAs are closely associated with epigenome programming during plant reproduction. Here, we review current knowledge on chromatin changes occurring during sporogenesis and gametogenesis, as well as early seed development in major flowering plant models. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

CRISPR-Cas Technologies and Applications in Food Bacteria.

PubMed

Stout, Emily; Klaenhammer, Todd; Barrangou, Rodolphe

2017-02-28

Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins form adaptive immune systems that occur in many bacteria and most archaea. In addition to protecting bacteria from phages and other invasive mobile genetic elements, CRISPR-Cas molecular machines can be repurposed as tool kits for applications relevant to the food industry. A primary concern of the food industry has long been the proper management of food-related bacteria, with a focus on both enhancing the outcomes of beneficial microorganisms such as starter cultures and probiotics and limiting the presence of detrimental organisms such as pathogens and spoilage microorganisms. This review introduces CRISPR-Cas as a novel set of technologies to manage food bacteria and offers insights into CRISPR-Cas biology. It primarily focuses on the applications of CRISPR-Cas systems and tools in starter cultures and probiotics, encompassing strain-typing, phage resistance, plasmid vaccination, genome editing, and antimicrobial activity.

Budding yeast for budding geneticists: a primer on the Saccharomyces cerevisiae model system.

PubMed

Duina, Andrea A; Miller, Mary E; Keeney, Jill B

2014-05-01

The budding yeast Saccharomyces cerevisiae is a powerful model organism for studying fundamental aspects of eukaryotic cell biology. This Primer article presents a brief historical perspective on the emergence of this organism as a premier experimental system over the course of the past century. An overview of the central features of the S. cerevisiae genome, including the nature of its genetic elements and general organization, is also provided. Some of the most common experimental tools and resources available to yeast geneticists are presented in a way designed to engage and challenge undergraduate and graduate students eager to learn more about the experimental amenability of budding yeast. Finally, a discussion of several major discoveries derived from yeast studies highlights the far-reaching impact that the yeast system has had and will continue to have on our understanding of a variety of cellular processes relevant to all eukaryotes, including humans.

Budding Yeast for Budding Geneticists: A Primer on the Saccharomyces cerevisiae Model System

PubMed Central

Duina, Andrea A.; Miller, Mary E.; Keeney, Jill B.

2014-01-01

The budding yeast Saccharomyces cerevisiae is a powerful model organism for studying fundamental aspects of eukaryotic cell biology. This Primer article presents a brief historical perspective on the emergence of this organism as a premier experimental system over the course of the past century. An overview of the central features of the S. cerevisiae genome, including the nature of its genetic elements and general organization, is also provided. Some of the most common experimental tools and resources available to yeast geneticists are presented in a way designed to engage and challenge undergraduate and graduate students eager to learn more about the experimental amenability of budding yeast. Finally, a discussion of several major discoveries derived from yeast studies highlights the far-reaching impact that the yeast system has had and will continue to have on our understanding of a variety of cellular processes relevant to all eukaryotes, including humans. PMID:24807111

Integrative analysis of 111 reference human epigenomes.

PubMed

Kundaje, Anshul; Meuleman, Wouter; Ernst, Jason; Bilenky, Misha; Yen, Angela; Heravi-Moussavi, Alireza; Kheradpour, Pouya; Zhang, Zhizhuo; Wang, Jianrong; Ziller, Michael J; Amin, Viren; Whitaker, John W; Schultz, Matthew D; Ward, Lucas D; Sarkar, Abhishek; Quon, Gerald; Sandstrom, Richard S; Eaton, Matthew L; Wu, Yi-Chieh; Pfenning, Andreas R; Wang, Xinchen; Claussnitzer, Melina; Liu, Yaping; Coarfa, Cristian; Harris, R Alan; Shoresh, Noam; Epstein, Charles B; Gjoneska, Elizabeta; Leung, Danny; Xie, Wei; Hawkins, R David; Lister, Ryan; Hong, Chibo; Gascard, Philippe; Mungall, Andrew J; Moore, Richard; Chuah, Eric; Tam, Angela; Canfield, Theresa K; Hansen, R Scott; Kaul, Rajinder; Sabo, Peter J; Bansal, Mukul S; Carles, Annaick; Dixon, Jesse R; Farh, Kai-How; Feizi, Soheil; Karlic, Rosa; Kim, Ah-Ram; Kulkarni, Ashwinikumar; Li, Daofeng; Lowdon, Rebecca; Elliott, GiNell; Mercer, Tim R; Neph, Shane J; Onuchic, Vitor; Polak, Paz; Rajagopal, Nisha; Ray, Pradipta; Sallari, Richard C; Siebenthall, Kyle T; Sinnott-Armstrong, Nicholas A; Stevens, Michael; Thurman, Robert E; Wu, Jie; Zhang, Bo; Zhou, Xin; Beaudet, Arthur E; Boyer, Laurie A; De Jager, Philip L; Farnham, Peggy J; Fisher, Susan J; Haussler, David; Jones, Steven J M; Li, Wei; Marra, Marco A; McManus, Michael T; Sunyaev, Shamil; Thomson, James A; Tlsty, Thea D; Tsai, Li-Huei; Wang, Wei; Waterland, Robert A; Zhang, Michael Q; Chadwick, Lisa H; Bernstein, Bradley E; Costello, Joseph F; Ecker, Joseph R; Hirst, Martin; Meissner, Alexander; Milosavljevic, Aleksandar; Ren, Bing; Stamatoyannopoulos, John A; Wang, Ting; Kellis, Manolis

2015-02-19

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Strategic patent analysis in plant biotechnology: terpenoid indole alkaloid metabolic engineering as a case study.

PubMed

Miralpeix, Bruna; Sabalza, Maite; Twyman, Richard M; Capell, Teresa; Christou, Paul

2014-02-01

The do-it-yourself patent search is a useful alternative to professional patent analysis particularly in the context of publicly funded projects where funds for IP activities may be limited. As a case study, we analysed patents related to the engineering of terpenoid indole alkaloid (TIA) metabolism in plants. We developed a focused search strategy to remove redundancy and reduce the workload without missing important and relevant patents. This resulted in the identification of approximately 50 key patents associated with TIA metabolic engineering in plants, which could form the basis of a more detailed freedom-to-operate analysis. The structural elements of this search strategy could easily be transferred to other contexts, making it a useful generic model for publicly funded research projects. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Implantable polymer/metal thin film structures for the localized treatment of cancer by Joule heating

NASA Astrophysics Data System (ADS)

Kan-Dapaah, Kwabena; Rahbar, Nima; Theriault, Christian; Soboyejo, Wole

2015-04-01

This paper presents an implantable polymer/metal alloy thin film structure for localized post-operative treatment of breast cancer. A combination of experiments and models is used to study the temperature changes due to Joule heating by patterned metallic thin films embedded in poly-dimethylsiloxane. The heat conduction within the device and the surrounding normal/cancerous breast tissue is modeled with three-dimensional finite element method (FEM). The FEM simulations are used to explore the potential effects of device geometry and Joule heating on the temperature distribution and lesion (thermal dose). The FEM model is validated using a gel model that mimics biological media. The predictions are also compared to prior results from in vitro studies and relevant in vivo studies in the literature. The implications of the results are discussed for the potential application of polymer/metal thin film structures in hyperthermic treatment of cancer.

High transconductance organic electrochemical transistors

PubMed Central

Khodagholy, Dion; Rivnay, Jonathan; Sessolo, Michele; Gurfinkel, Moshe; Leleux, Pierre; Jimison, Leslie H.; Stavrinidou, Eleni; Herve, Thierry; Sanaur, Sébastien; Owens, Róisín M.; Malliaras, George G.

2013-01-01

The development of transistors with high gain is essential for applications ranging from switching elements and drivers to transducers for chemical and biological sensing. Organic transistors have become well-established based on their distinct advantages, including ease of fabrication, synthetic freedom for chemical functionalization, and the ability to take on unique form factors. These devices, however, are largely viewed as belonging to the low-end of the performance spectrum. Here we present organic electrochemical transistors with a transconductance in the mS range, outperforming transistors from both traditional and emerging semiconductors. The transconductance of these devices remains fairly constant from DC up to a frequency of the order of 1 kHz, a value determined by the process of ion transport between the electrolyte and the channel. These devices, which continue to work even after being crumpled, are predicted to be highly relevant as transducers in biosensing applications. PMID:23851620

Insecticide Resistance and Malaria Vector Control: The Importance of Fitness Cost Mechanisms in Determining Economically Optimal Control Trajectories

PubMed Central

Brown, Zachary S.; Dickinson, Katherine L.; Kramer, Randall A.

2014-01-01

The evolutionary dynamics of insecticide resistance in harmful arthropods has economic implications, not only for the control of agricultural pests (as has been well studied), but also for the control of disease vectors, such as malaria-transmitting Anopheles mosquitoes. Previous economic work on insecticide resistance illustrates the policy relevance of knowing whether insecticide resistance mutations involve fitness costs. Using a theoretical model, this article investigates economically optimal strategies for controlling malaria-transmitting mosquitoes when there is the potential for mosquitoes to evolve resistance to insecticides. Consistent with previous literature, we find that fitness costs are a key element in the computation of economically optimal resistance management strategies. Additionally, our models indicate that different biological mechanisms underlying these fitness costs (e.g., increased adult mortality and/or decreased fecundity) can significantly alter economically optimal resistance management strategies. PMID:23448053

Visualising associations between paired ‘omics’ data sets

PubMed Central

2012-01-01

Background Each omics platform is now able to generate a large amount of data. Genomics, proteomics, metabolomics, interactomics are compiled at an ever increasing pace and now form a core part of the fundamental systems biology framework. Recently, several integrative approaches have been proposed to extract meaningful information. However, these approaches lack of visualisation outputs to fully unravel the complex associations between different biological entities. Results The multivariate statistical approaches ‘regularized Canonical Correlation Analysis’ and ‘sparse Partial Least Squares regression’ were recently developed to integrate two types of highly dimensional ‘omics’ data and to select relevant information. Using the results of these methods, we propose to revisit few graphical outputs to better understand the relationships between two ‘omics’ data and to better visualise the correlation structure between the different biological entities. These graphical outputs include Correlation Circle plots, Relevance Networks and Clustered Image Maps. We demonstrate the usefulness of such graphical outputs on several biological data sets and further assess their biological relevance using gene ontology analysis. Conclusions Such graphical outputs are undoubtedly useful to aid the interpretation of these promising integrative analysis tools and will certainly help in addressing fundamental biological questions and understanding systems as a whole. Availability The graphical tools described in this paper are implemented in the freely available R package mixOmics and in its associated web application. PMID:23148523

Biomarkers of nanomaterial exposure and effect: current status

NASA Astrophysics Data System (ADS)

Iavicoli, Ivo; Leso, Veruscka; Manno, Maurizio; Schulte, Paul A.

2014-03-01

Recent advances in nanotechnology have induced a widespread production and application of nanomaterials. As a consequence, an increasing number of workers are expected to undergo exposure to these xenobiotics, while the possible hazards to their health remain not being completely understood. In this context, biological monitoring may play a key role not only to identify potential hazards from and to evaluate occupational exposure to nanomaterials, but also to detect their early biological effects to better assess and manage risks of exposure in respect of the health of workers. Therefore, the aim of this review is to provide a critical evaluation of potential biomarkers of nanomaterial exposure and effect investigated in human and animal studies. Concerning exposure biomarkers, internal dose of metallic or metal oxide nanoparticle exposure may be assessed measuring the elemental metallic content in blood or urine or other biological materials, whereas specific molecules may be carefully evaluated in target tissues as possible biomarkers of biologically effective dose. Oxidative stress biomarkers, such as 8-hydroxy-deoxy-guanosine, genotoxicity biomarkers, and inflammatory response indicators may also be useful, although not specific, as biomarkers of nanomaterial early adverse health effects. Finally, potential biomarkers from "omic" technologies appear to be quite innovative and greatly relevant, although mechanistic, ethical, and practical issues should all be resolved before their routine application in occupational settings could be implemented. Although all these findings are interesting, they point out the need for further research to identify and possibly validate sensitive and specific biomarkers of exposure and effect, suitable for future use in occupational biomonitoring programs. A valuable contribution may derive from the studies investigating the biological behavior of nanomaterials and the factors influencing their toxicokinetics and reactivity. In this context, the application of the most recent advances in analytical chemistry and biochemistry to the biological monitoring of nanomaterial exposure may be also useful to detect and define patterns and mechanisms of early nanospecific biochemical alterations.

PREFACE Physical Aspects of Developmental Biology: 21st Century Perspectives 'On Growth and Form' Physical Aspects of Developmental Biology: 21st Century Perspectives 'On Growth and Form'

NASA Astrophysics Data System (ADS)

Hutson, M. Shane

2008-04-01

There is a long and circuitous route from an organism_s genome to its steady-state adult form—all of which falls under the wide umbrella of developmental biology. Given this breadth, how does one answer the question: what is the mechanism by which developmental event X takes place? The answer depends strongly on what one considers an acceptable explanation. In some scientific circles, the answer would focus on the regulatory genes involved. In others, the focus would be on the signaling pathways activated, or on the associated cellular movements, or maybe even on the intra- and intercellular forces. In the long term, the goal must be to provide an explanation that connects all of these perspectives. During the last several decades, molecular biology has made enormous progress towards understanding development from the genome-side. Unfortunately, progress has been much slower on the relevant physical biology—which had a huge head start in the late 19th century age of developmental mechanics. It is just a slight exaggeration to claim that we_ve made little progress on the physical side since D_Arcy Thompson_s On Growth and Form in 1917. Hopefully, such statements will be recognized as large exaggerations in years to come as developmental mechanics is now in resurgence. This special issue of Physical Biology brings together current work in developmental mechanics from an international cadre of scientists—including physicists, biologists and engineers. The works include both models and experiments. They span scales from subcellular microrheology to finite element models of entire embryos. I hope that students looking for one of these articles will dive into the rest. The field of developmental mechanics is in the process of training a new generation of students who are comfortable with both the necessary biology and physics. Enormous opportunities are available for those who can work across those traditional disciplinary boundaries.

Conservation biology in Asia: the major policy challenges.

PubMed

McNeely, Jeffrey A; Kapoor-Vijay, Promila; Zhi, Lu; Olsvig-Whittaker, Linda; Sheikh, Kashif M; Smith, Andrew T

2009-08-01

With about half the world's human population and booming economies, Asia faces numerous challenges to its biodiversity. The Asia Section of the Society for Conservation Biology has identified some key policy issues in which significant progress can be made. These include developing new sources of funding for forest conservation; identifying potential impacts of energy alternatives on the conservation of biodiversity; curbing the trade in endangered species of plants and animals; a special focus on the conservation of mountain biodiversity; enhancing relevant research; ensuring that conservation biology contributes to major international conventions and funding mechanisms; using conservation biology to build a better understanding of zoonotic diseases; more effectively addressing human-animal conflicts; enhancing community-based conservation; and using conservation biology to help address the pervasive water-deficit problems in much of Asia. These challenges can be met through improved regional cooperation among the relevant stakeholders.

Urokinase-receptor (u-PAR): an essential player in multiple games of cancer: a review on its role in tumor progression, invasion, metastasis, proliferation/dormancy, clinical outcome and minimal residual disease.

PubMed

Laufs, Stephanie; Schumacher, Jens; Allgayer, Heike

2006-08-01

The relevance of the u-PA system in mediating tumor-associated proteolysis, invasion and metastasis, amongst other phenomena associated with tumor progression, has been clearly demonstrated in diverse cancer entities. This review will update on the biological and clinical relevance of the urokinase-receptor (u-PAR). Specifically, the article focuses on the potential importance of u-PAR for the development of minimal residual disease in solid cancer, and in this context reviews the biological relevance of the u-PAR for tumor cell dormancy. Furthermore, transcriptional mechanisms regulating u-PAR in vitro and in vivo, and their potential clinical and therapeutic relevance in gastrointestinal cancers, are elucidated.

Curtailing the high rate of late-stage attrition of investigational therapeutics against unprecedented targets in patients with lung and other malignancies.

PubMed

Rowinsky, Eric K

2004-06-15

A greater understanding of the pathogenesis and biology of cancer coupled with major advances in biotechnology has resulted in the identification of rationally designed, target-based (RDTB) anticancer therapeutics, ushering in new therapeutic opportunities and high expectations for the future as well as developmental challenges. Because these agents appear to principally target malignant cells, it is expected that they will produce less toxicity at clinically effective doses than nonspecific cytotoxic agents, but their target requirements are likely to be much more stringent. The innate complexity of the networks that contain elements targeted by these agents also decreases the probability that any single therapeutic manipulation will result in robust clinical activity and success when used alone, particularly in patients with solid malignancies that have multiple relevant signaling aberrations. In contrast, proof of principle and robust antitumor activity may be most efficiently demonstrated in nonrandomized evaluations involving tumors that are principally driven by aberrations of the specific target. The predominant therapeutic manifestation of RDTB agents in preclinical studies is due to decreased tumor growth rates and will likely be similar in the clinic; however, such manifestations are not readily detectable and quantifiable using nonrandomized clinical evaluations. To curtail the increasing rate of late-stage attrition of RDTB agents, which, if maintained, will stymie progress in cancer therapy, the design of initial nonrandomized evaluations, particularly the selection of tumors and patients, must be guided by the principal biological features of the agents. Next, evaluations, some of which must be randomized, can be performed in a wide range of tumor types, depending on the presence and relevance of the target. To validate the concept of RDTB therapeutics and to realize their full potential, radically different development, evaluation, and regulatory paradigms must be adopted.

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…

Exemplary Programs in Secondary School Biology.

ERIC Educational Resources Information Center

McComas, William F.; Penick, John E.

1989-01-01

Summarizes 10 exemplary programs which address topics on individualized biology, a modified team approach, limnology, physical anthropology, the relevance of biology to society, ecology, and health. Provides names and addresses of contact persons for further information. Units cover a broad range of abilities and activities. (RT)

Diagnosing oceanic nutrient deficiency

PubMed Central

2016-01-01

The supply of a range of nutrient elements to surface waters is an important driver of oceanic production and the subsequent linked cycling of the nutrients and carbon. Relative deficiencies of different nutrients with respect to biological requirements, within both surface and internal water masses, can be both a key indicator and driver of the potential for these nutrients to become limiting for the production of new organic material in the upper ocean. The availability of high-quality, full-depth and global-scale datasets on the concentrations of a wide range of both macro- and micro-nutrients produced through the international GEOTRACES programme provides the potential for estimation of multi-element deficiencies at unprecedented scales. Resultant coherent large-scale patterns in diagnosed deficiency can be linked to the interacting physical–chemical–biological processes which drive upper ocean nutrient biogeochemistry. Calculations of ranked deficiencies across multiple elements further highlight important remaining uncertainties in the stoichiometric plasticity of nutrient ratios within oceanic microbial systems and caveats with regards to linkages to upper ocean nutrient limitation. This article is part of the themed issue ‘Biological and climatic impacts of ocean trace element chemistry’. PMID:29035255

Diagnosing oceanic nutrient deficiency

NASA Astrophysics Data System (ADS)

Moore, C. Mark

2016-11-01

The supply of a range of nutrient elements to surface waters is an important driver of oceanic production and the subsequent linked cycling of the nutrients and carbon. Relative deficiencies of different nutrients with respect to biological requirements, within both surface and internal water masses, can be both a key indicator and driver of the potential for these nutrients to become limiting for the production of new organic material in the upper ocean. The availability of high-quality, full-depth and global-scale datasets on the concentrations of a wide range of both macro- and micro-nutrients produced through the international GEOTRACES programme provides the potential for estimation of multi-element deficiencies at unprecedented scales. Resultant coherent large-scale patterns in diagnosed deficiency can be linked to the interacting physical-chemical-biological processes which drive upper ocean nutrient biogeochemistry. Calculations of ranked deficiencies across multiple elements further highlight important remaining uncertainties in the stoichiometric plasticity of nutrient ratios within oceanic microbial systems and caveats with regards to linkages to upper ocean nutrient limitation. This article is part of the themed issue 'Biological and climatic impacts of ocean trace element chemistry'.

Identifying relevant data for a biological database: handcrafted rules versus machine learning.

PubMed

Sehgal, Aditya Kumar; Das, Sanmay; Noto, Keith; Saier, Milton H; Elkan, Charles

2011-01-01

With well over 1,000 specialized biological databases in use today, the task of automatically identifying novel, relevant data for such databases is increasingly important. In this paper, we describe practical machine learning approaches for identifying MEDLINE documents and Swiss-Prot/TrEMBL protein records, for incorporation into a specialized biological database of transport proteins named TCDB. We show that both learning approaches outperform rules created by hand by a human expert. As one of the first case studies involving two different approaches to updating a deployed database, both the methods compared and the results will be of interest to curators of many specialized databases.

A Road Less Traveled By: Exploring a Decade of Ellman Chemistry

PubMed Central

Shelat, Anang A.; Guy, R. Kiplin

2009-01-01

The Ellman group has been one of the most influential in the development and widespread adoption of combinatorial chemistry techniques for biomedical research. Their work has included substantial methodological development for library synthesis with a particular focus on new scaffolds rationally targeted to biomolecules of interest and biologically relevant natural products. Herein we analyze a representative set of libraries from this group with respect to their biological and biomedical relevance in comparison to existing drugs and probe compounds. This analysis reveals that the Ellman group has not only provided new methodologies to the community but also provided libraries with unique potential for further biological study. PMID:18343129

A computational kinetic model of diffusion for molecular systems.

PubMed

Teo, Ivan; Schulten, Klaus

2013-09-28

Regulation of biomolecular transport in cells involves intra-protein steps like gating and passage through channels, but these steps are preceded by extra-protein steps, namely, diffusive approach and admittance of solutes. The extra-protein steps develop over a 10-100 nm length scale typically in a highly particular environment, characterized through the protein's geometry, surrounding electrostatic field, and location. In order to account for solute energetics and mobility of solutes in this environment at a relevant resolution, we propose a particle-based kinetic model of diffusion based on a Markov State Model framework. Prerequisite input data consist of diffusion coefficient and potential of mean force maps generated from extensive molecular dynamics simulations of proteins and their environment that sample multi-nanosecond durations. The suggested diffusion model can describe transport processes beyond microsecond duration, relevant for biological function and beyond the realm of molecular dynamics simulation. For this purpose the systems are represented by a discrete set of states specified by the positions, volumes, and surface elements of Voronoi grid cells distributed according to a density function resolving the often intricate relevant diffusion space. Validation tests carried out for generic diffusion spaces show that the model and the associated Brownian motion algorithm are viable over a large range of parameter values such as time step, diffusion coefficient, and grid density. A concrete application of the method is demonstrated for ion diffusion around and through the Eschericia coli mechanosensitive channel of small conductance ecMscS.

Bridging Physics and Biology Using Resistance and Axons

ERIC Educational Resources Information Center

Dyer, Joshua M.

2014-01-01

When teaching physics, it is often difficult to get biology-oriented students to see the relevance of physics. A complaint often heard is that biology students are required to take physics for the Medical College Admission Test (MCAT) as part of a "weeding out" process, but that they don't feel like they need physics for biology. Despite…

Making Research Fly in Schools: "Drosophila" as a Powerful Modern Tool for Teaching Biology

ERIC Educational Resources Information Center

Harbottle, Jennifer; Strangward, Patrick; Alnuamaani, Catherine; Lawes, Surita; Patel, Sanjai; Prokop, Andreas

2016-01-01

The "droso4schools" project aims to introduce the fruit fly "Drosophila" as a powerful modern teaching tool to convey curriculum-relevant specifications in biology lessons. Flies are easy and cheap to breed and have been at the forefront of biology research for a century, providing unique conceptual understanding of biology and…

Water-quality, bed-sediment, and biological data (October 2012 through September 2013) and statistical summaries of data for streams in the Clark Fork Basin, Montana

USGS Publications Warehouse

Dodge, Kent A.; Hornberger, Michelle I.; Dyke, Jessica

2014-01-01

This report presents the analytical results and quality-assurance data for water-quality, bed-sediment, and biota samples collected at sites from October 2012 through September 2013. Water-quality data include concentrations of selected major ions, trace elements, and suspended sediment. Turbidity and dissolved organic carbon were analyzed for water samples collected at the four sites where seasonal daily values of turbidity were being determined. Daily values of mean suspended-sediment concentration and suspended-sediment discharge were determined for four sites. Bed-sediment data include trace-element concentrations in the fine-grained fraction. Biological data include trace-element concentrations in whole-body tissue of aquatic benthic insects. Statistical sum-maries of water-quality, bed-sediment, and biological data for sites in the upper Clark Fork Basin are provided for the period of record.

Optimization of hCFTR Lung Expression in Mice Using DNA Nanoparticles

PubMed Central

Padegimas, Linas; Kowalczyk, Tomasz H; Adams, Sam; Gedeon, Chris R; Oette, Sharon M; Dines, Karla; Hyatt, Susannah L; Sesenoglu-Laird, Ozge; Tyr, Olena; Moen, Robert C; Cooper, Mark J

2012-01-01

Efficient and prolonged human cystic fibrosis transmembrane conductance regulator (hCFTR) expression is a major goal for cystic fibrosis (CF) lung therapy. A hCFTR expression plasmid was optimized as a payload for compacted DNA nanoparticles formulated with polyethylene glycol (PEG)-substituted 30-mer lysine peptides. A codon-optimized and CpG-reduced hCFTR synthetic gene (CO-CFTR) was placed in a polyubiquitin C expression plasmid. Compared to hCFTR complementary DNA (cDNA), CO-CFTR produced a ninefold increased level of hCFTR protein in transfected HEK293 cells and, when compacted as DNA nanoparticles, produced a similar improvement in lung mRNA expression in Balb/c and fatty acid binding protein promoter (FABP) CF mice, although expression duration was transient. Various vector modifications were tested to extend duration of CO-CFTR expression. A novel prolonged expression (PE) element derived from the bovine growth hormone (BGH) gene 3′ flanking sequence produced prolonged expression of CO-CFTR mRNA at biologically relevant levels. A time course study in the mouse lung revealed that CO-CFTR mRNA did not change significantly, with CO-CFTR/mCFTR geometric mean ratios of 94% on day 2, 71% on day 14, 53% on day 30, and 14% on day 59. Prolonged CO-CFTR expression is dependent on the orientation of the PE element and its transcription, is not specific to the UbC promoter, and is less dependent on other vector backbone elements. PMID:21952168

Ski acts as a co-repressor with Smad2 and Smad3 to regulate the response to type β transforming growth factor

PubMed Central

Xu, Weidong; Angelis, Konstantina; Danielpour, David; Haddad, Maher M.; Bischof, Oliver; Campisi, Judith; Stavnezer, Ed; Medrano, Estela E.

2000-01-01

The c-ski protooncogene encodes a transcription factor that binds DNA only in association with other proteins. To identify co-binding proteins, we performed a yeast two-hybrid screen. The results of the screen and subsequent co-immunoprecipitation studies identified Smad2 and Smad3, two transcriptional activators that mediate the type β transforming growth factor (TGF-β) response, as Ski-interacting proteins. In Ski-transformed cells, all of the Ski protein was found in Smad3-containing complexes that accumulated in the nucleus in the absence of added TGF-β. DNA binding assays showed that Ski, Smad2, Smad3, and Smad4 form a complex with the Smad/Ski binding element GTCTAGAC (SBE). Ski repressed TGF-β-induced expression of 3TP-Lux, the natural plasminogen activator inhibitor 1 promoter and of reporter genes driven by the SBE and the related CAGA element. In addition, Ski repressed a TGF-β-inducible promoter containing AP-1 (TRE) elements activated by a combination of Smads, Fos, and/or Jun proteins. Ski also repressed synergistic activation of promoters by combinations of Smad proteins but failed to repress in the absence of Smad4. Thus, Ski acts in opposition to TGF-β-induced transcriptional activation by functioning as a Smad-dependent co-repressor. The biological relevance of this transcriptional repression was established by showing that overexpression of Ski abolished TGF-β-mediated growth inhibition in a prostate-derived epithelial cell line. PMID:10811875

Ski acts as a co-repressor with Smad2 and Smad3 to regulate the response to type beta transforming growth factor.

PubMed

Xu, W; Angelis, K; Danielpour, D; Haddad, M M; Bischof, O; Campisi, J; Stavnezer, E; Medrano, E E

2000-05-23

The c-ski protooncogene encodes a transcription factor that binds DNA only in association with other proteins. To identify co-binding proteins, we performed a yeast two-hybrid screen. The results of the screen and subsequent co-immunoprecipitation studies identified Smad2 and Smad3, two transcriptional activators that mediate the type beta transforming growth factor (TGF-beta) response, as Ski-interacting proteins. In Ski-transformed cells, all of the Ski protein was found in Smad3-containing complexes that accumulated in the nucleus in the absence of added TGF-beta. DNA binding assays showed that Ski, Smad2, Smad3, and Smad4 form a complex with the Smad/Ski binding element GTCTAGAC (SBE). Ski repressed TGF-beta-induced expression of 3TP-Lux, the natural plasminogen activator inhibitor 1 promoter and of reporter genes driven by the SBE and the related CAGA element. In addition, Ski repressed a TGF-beta-inducible promoter containing AP-1 (TRE) elements activated by a combination of Smads, Fos, and/or Jun proteins. Ski also repressed synergistic activation of promoters by combinations of Smad proteins but failed to repress in the absence of Smad4. Thus, Ski acts in opposition to TGF-beta-induced transcriptional activation by functioning as a Smad-dependent co-repressor. The biological relevance of this transcriptional repression was established by showing that overexpression of Ski abolished TGF-beta-mediated growth inhibition in a prostate-derived epithelial cell line.

Enhancement of COPD biological networks using a web-based collaboration interface

PubMed Central

Boue, Stephanie; Fields, Brett; Hoeng, Julia; Park, Jennifer; Peitsch, Manuel C.; Schlage, Walter K.; Talikka, Marja; Binenbaum, Ilona; Bondarenko, Vladimir; Bulgakov, Oleg V.; Cherkasova, Vera; Diaz-Diaz, Norberto; Fedorova, Larisa; Guryanova, Svetlana; Guzova, Julia; Igorevna Koroleva, Galina; Kozhemyakina, Elena; Kumar, Rahul; Lavid, Noa; Lu, Qingxian; Menon, Swapna; Ouliel, Yael; Peterson, Samantha C.; Prokhorov, Alexander; Sanders, Edward; Schrier, Sarah; Schwaitzer Neta, Golan; Shvydchenko, Irina; Tallam, Aravind; Villa-Fombuena, Gema; Wu, John; Yudkevich, Ilya; Zelikman, Mariya

2015-01-01

The construction and application of biological network models is an approach that offers a holistic way to understand biological processes involved in disease. Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the airways for which therapeutic options currently are limited after diagnosis, even in its earliest stage. COPD network models are important tools to better understand the biological components and processes underlying initial disease development. With the increasing amounts of literature that are now available, crowdsourcing approaches offer new forms of collaboration for researchers to review biological findings, which can be applied to the construction and verification of complex biological networks. We report the construction of 50 biological network models relevant to lung biology and early COPD using an integrative systems biology and collaborative crowd-verification approach. By combining traditional literature curation with a data-driven approach that predicts molecular activities from transcriptomics data, we constructed an initial COPD network model set based on a previously published non-diseased lung-relevant model set. The crowd was given the opportunity to enhance and refine the networks on a website ( https://bionet.sbvimprover.com/) and to add mechanistic detail, as well as critically review existing evidence and evidence added by other users, so as to enhance the accuracy of the biological representation of the processes captured in the networks. Finally, scientists and experts in the field discussed and refined the networks during an in-person jamboree meeting. Here, we describe examples of the changes made to three of these networks: Neutrophil Signaling, Macrophage Signaling, and Th1-Th2 Signaling. We describe an innovative approach to biological network construction that combines literature and data mining and a crowdsourcing approach to generate a comprehensive set of COPD-relevant models that can be used to help understand the mechanisms related to lung pathobiology. Registered users of the website can freely browse and download the networks. PMID:25767696

Enhancement of COPD biological networks using a web-based collaboration interface.

PubMed

Boue, Stephanie; Fields, Brett; Hoeng, Julia; Park, Jennifer; Peitsch, Manuel C; Schlage, Walter K; Talikka, Marja; Binenbaum, Ilona; Bondarenko, Vladimir; Bulgakov, Oleg V; Cherkasova, Vera; Diaz-Diaz, Norberto; Fedorova, Larisa; Guryanova, Svetlana; Guzova, Julia; Igorevna Koroleva, Galina; Kozhemyakina, Elena; Kumar, Rahul; Lavid, Noa; Lu, Qingxian; Menon, Swapna; Ouliel, Yael; Peterson, Samantha C; Prokhorov, Alexander; Sanders, Edward; Schrier, Sarah; Schwaitzer Neta, Golan; Shvydchenko, Irina; Tallam, Aravind; Villa-Fombuena, Gema; Wu, John; Yudkevich, Ilya; Zelikman, Mariya

2015-01-01

The construction and application of biological network models is an approach that offers a holistic way to understand biological processes involved in disease. Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the airways for which therapeutic options currently are limited after diagnosis, even in its earliest stage. COPD network models are important tools to better understand the biological components and processes underlying initial disease development. With the increasing amounts of literature that are now available, crowdsourcing approaches offer new forms of collaboration for researchers to review biological findings, which can be applied to the construction and verification of complex biological networks. We report the construction of 50 biological network models relevant to lung biology and early COPD using an integrative systems biology and collaborative crowd-verification approach. By combining traditional literature curation with a data-driven approach that predicts molecular activities from transcriptomics data, we constructed an initial COPD network model set based on a previously published non-diseased lung-relevant model set. The crowd was given the opportunity to enhance and refine the networks on a website ( https://bionet.sbvimprover.com/) and to add mechanistic detail, as well as critically review existing evidence and evidence added by other users, so as to enhance the accuracy of the biological representation of the processes captured in the networks. Finally, scientists and experts in the field discussed and refined the networks during an in-person jamboree meeting. Here, we describe examples of the changes made to three of these networks: Neutrophil Signaling, Macrophage Signaling, and Th1-Th2 Signaling. We describe an innovative approach to biological network construction that combines literature and data mining and a crowdsourcing approach to generate a comprehensive set of COPD-relevant models that can be used to help understand the mechanisms related to lung pathobiology. Registered users of the website can freely browse and download the networks.

Simultaneously Synchrotron X-ray Fluorescence and Ptychographic Imaging of Frozen Biological Single Cells

DOE PAGES

Chen, S.; Deng, J.; Nashed, Y. S. G.; ...

2016-07-25

Bionanoprobe (BNP), a hard x-ray fluorescence sample-scanning nanoprobe at the Advanced Photon Source of Argonne National Laboratory, has been used to quantitatively study elemental distributions in biological cells with sub-100 nm spatial resolution and high sensitivity. Cryogenic conditions enable biological samples to be studied in their frozen-hydrated state with both ultrastructure and elemental distributions more faithfully preserved compared to conventional chemical fixation or dehydration methods. Furthermore, radiation damage is reduced in two ways: the diffusion rate of free radicals is decreased at low temperatures; and the sample is embedded in vitrified ice, which reduces mass loss.

First-principles modeling of biological systems and structure-based drug-design.

PubMed

Sgrignani, Jacopo; Magistrato, Alessandra

2013-03-01

Molecular modeling techniques play a relevant role in drug design providing detailed information at atomistic level on the structural, dynamical, mechanistic and electronic properties of biological systems involved in diseases' onset, integrating and supporting commonly used experimental approaches. These information are often not accessible to the experimental techniques taken singularly, but are of crucial importance for drug design. Due to the enormous increase of the computer power in the last decades, quantum mechanical (QM) or first-principles-based methods have become often used to address biological issues of pharmaceutical relevance, providing relevant information for drug design. Due to their complexity and their size, biological systems are often investigated by means of a mixed quantum-classical (QM/MM) approach, which treats at an accurate QM level a limited chemically relevant portion of the system and at the molecular mechanics (MM) level the remaining of the biomolecule and its environment. This method provides a good compromise between computational cost and accuracy, allowing to characterize the properties of the biological system and the (free) energy landscape of the process in study with the accuracy of a QM description. In this review, after a brief introduction of QM and QM/MM methods, we will discuss few representative examples, taken from our work, of the application of these methods in the study of metallo-enzymes of pharmaceutical interest, of metal-containing anticancer drugs targeting the DNA as well as of neurodegenerative diseases. The information obtained from these studies may provide the basis for a rationale structure-based drug design of new and more efficient inhibitors or drugs.

Gene network biological validity based on gene-gene interaction relevance.

PubMed

Gómez-Vela, Francisco; Díaz-Díaz, Norberto

2014-01-01

In recent years, gene networks have become one of the most useful tools for modeling biological processes. Many inference gene network algorithms have been developed as techniques for extracting knowledge from gene expression data. Ensuring the reliability of the inferred gene relationships is a crucial task in any study in order to prove that the algorithms used are precise. Usually, this validation process can be carried out using prior biological knowledge. The metabolic pathways stored in KEGG are one of the most widely used knowledgeable sources for analyzing relationships between genes. This paper introduces a new methodology, GeneNetVal, to assess the biological validity of gene networks based on the relevance of the gene-gene interactions stored in KEGG metabolic pathways. Hence, a complete KEGG pathway conversion into a gene association network and a new matching distance based on gene-gene interaction relevance are proposed. The performance of GeneNetVal was established with three different experiments. Firstly, our proposal is tested in a comparative ROC analysis. Secondly, a randomness study is presented to show the behavior of GeneNetVal when the noise is increased in the input network. Finally, the ability of GeneNetVal to detect biological functionality of the network is shown.

Emergy of the Global Biogeochemical Cycles of Biologically Active Elements

EPA Science Inventory

Accurate estimates of the emergy of elemental flows are needed to accurately evaluate the far field effects of anthropogenic wastes. The transformity and specific emergy of the elements and of their different chemical species is also needed to quantify the inputs to many producti...

Analysis of nutrition-relevant trace elements in human blood and serum by means of total reflection X-ray fluorescence (TXRF) spectroscopy

NASA Astrophysics Data System (ADS)

Stosnach, Hagen; Mages, Margarete

2009-04-01

In clinical service laboratories, one of the most common analytical tasks with regard to inorganic traces is the determination of the nutrition-relevant elements Fe, Cu, Zn, and Se. Because of the high numbers of samples and the commercial character of these analyses, a time-consuming sample preparation must be avoided. In this presentation, the results of total reflection X-ray fluorescence measurements with a low-power system and different sample preparation procedures are compared with those derived from analysis with common methods like Atomic Absorption Spectroscopy (AAS) and Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The results of these investigations indicate that the optimal total reflection X-ray fluorescence analysis of the nutrition-relevant elements Fe, Cu, Zn, and Se can be performed by preparing whole blood and serum samples after dilution with ultrapure water and transferring 10 μl of internally standardized sample to an unsiliconized quartz glass sample carrier with subsequent drying in a laboratory oven. Suitable measurement time was found to be 600 s. The enhanced sample preparation by means of microwave or open digestion, in parts combined with cold plasma ashing, led to an improvement of detection limits by a factor of 2 for serum samples while for whole blood samples an improvement was only observed for samples prepared by means of microwave digestion. As the matrix elements P, S, Cl, and for whole blood Fe have a major influence on the detection limits, most probably a further enhancement of analytical quality requires the removal of the organic matrix. However, for the routine analysis of the nutrition-relevant elements, the dilution preparation was found to be sufficient.

Self-Relevance Constructions of Biology Concepts: Meaning-Making and Identity-Formation

ERIC Educational Resources Information Center

Davidson, Yonaton Sahar

2018-01-01

Recent research supports the benefit of students' construction of relevance through writing about the connection of content to their life. However, most such research defines relevance narrowly as utility value--perceived instrumentality of the content to the student's career goals. Furthermore, the scope of phenomenological and conceptual…

[The common bed bug (Cimex lectularius) - biology, medical relevance, possibilities for the detection and control].

PubMed

Rupeš, V; Vlčková, J; Holý, O; Horáková, D; Azeem, K; Kollárová, H

2017-01-01

Bed bugs have become a major concern worldwide in the 21st century and are therefore intensively investigated. The new findings not only extend the knowledge of their biology, medical relevance, and causes of the resurgence, but also can be used in bed bug management. A brief overview is provided of some of the most important research results and opinions, published in the last few years in prestigious international journals.

The road not taken: Applications of fluorescence spectroscopy and electronic structure theory to systems of materials and biological relevance

NASA Astrophysics Data System (ADS)

Carlson, Philip Joseph

Applications of Fluorescence Spectroscopy and Electronic Structure Theory to Systems of Materials and Biological Relevance. The photophysics of curcumin was studied in micelles and the solvation dynamics were probed. The high-energy ionic liquid HEATN was also studied using the fragment molecular orbital method. The solvation dynamics of the HEATN system were determined. This marks the first study of the solvation dynamics in a triazolium ionic liquid system.

Developmental Testing of Liquid and Gaseous/Vaporous Decontamination on Bacterial Spores and Other Biological Warfare Agents on Military Relevant Surfaces

DTIC Science & Technology

2016-02-11

process ( gas /vapor or liquid ), sampling will be conducted as soon as possible. Samples will be incubated for 12 to 48 hours (depending on the...Final 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Test Operations Procedure (TOP) 08-2-065 Developmental Testing of Liquid and Gaseous...biological decontamination protocol to analyze the efficacy of liquid and gaseous/vaporous decontaminants on military-relevant surfaces. The

Polymer monolithic capillary microextraction combined on-line with inductively coupled plasma MS for the determination of trace rare earth elements in biological samples.

PubMed

Zhang, Lin; Chen, Beibei; He, Man; Hu, Bin

2013-07-01

A rapid and sensitive method based on polymer monolithic capillary microextraction combined on-line with microconcentric nebulization inductively coupled plasma MS has been developed for the determination of trace/ultratrace rare earth elements in biological samples. For this purpose, the iminodiacetic acid modified poly(glycidyl methacrylate-trimethylolpropane trimethacrylate) monolithic capillary was prepared and characterized by SEM and FTIR spectroscopy. Factors affecting the extraction efficiency, such as sample pH, sample flow rate, sample/eluent volume, and coexisting ions were investigated in detail. Under the optimal conditions, the LODs for rare earth elements were in the range of 0.08 (Er) to 0.97 ng/L (Nd) with a sampling frequency of 8.5 h(-1), and the RSDs were between 1.5% (Sm) and 7.4% (Nd) (c = 20 ng/L, n = 7). The proposed method was successfully applied to the analysis of trace/ultratrace rare earth elements in human urine and serum samples, and the recoveries for the spiked samples were in the range of 82-105%. The developed method was simple, rapid, sensitive, and favorable for the analysis of trace/ultratrace rare earth elements in biological samples with limited sample volume. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

As Clear as Mud? Determining the Diversity and Prevalence of Prophages in the Draft Genomes of Estuarine Isolates of Clostridium difficile.

PubMed

Hargreaves, Katherine R; Otieno, James R; Thanki, Anisha; Blades, Matthew J; Millard, Andrew D; Browne, Hilary P; Lawley, Trevor D; Clokie, Martha R J

2015-05-27

The bacterium Clostridium difficile is a significant cause of nosocomial infections worldwide. The pathogenic success of this organism can be attributed to its flexible genome which is characterized by the exchange of mobile genetic elements, and by ongoing genome evolution. Despite its pathogenic status, C. difficile can also be carried asymptomatically, and has been isolated from natural environments such as water and sediments where multiple strain types (ribotypes) are found in close proximity. These include ribotypes which are associated with disease, as well as those that are less commonly isolated from patients. Little is known about the genomic content of strains in such reservoirs in the natural environment. In this study, draft genomes have been generated for 13 C. difficile isolates from estuarine sediments including clinically relevant and environmental associated types. To identify the genetic diversity within this strain collection, whole-genome comparisons were performed using the assemblies. The strains are highly genetically diverse with regards to the C. difficile "mobilome," which includes transposons and prophage elements. We identified a novel transposon-like element in two R078 isolates. Multiple, related and unrelated, prophages were detected in isolates across ribotype groups, including two novel prophage elements and those related to the transducing phage φC2. The susceptibility of these isolates to lytic phage infection was tested using a panel of characterized phages found from the same locality. In conclusion, estuarine sediments are a source of genetically diverse C. difficile strains with a complex network of prophages, which could contribute to the emergence of new strains in clinics. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Relevance Rank Platform (RRP) for Functional Filtering of High Content Protein-Protein Interaction Data.

PubMed

Pokharel, Yuba Raj; Saarela, Jani; Szwajda, Agnieszka; Rupp, Christian; Rokka, Anne; Lal Kumar Karna, Shibendra; Teittinen, Kaisa; Corthals, Garry; Kallioniemi, Olli; Wennerberg, Krister; Aittokallio, Tero; Westermarck, Jukka

2015-12-01

High content protein interaction screens have revolutionized our understanding of protein complex assembly. However, one of the major challenges in translation of high content protein interaction data is identification of those interactions that are functionally relevant for a particular biological question. To address this challenge, we developed a relevance ranking platform (RRP), which consist of modular functional and bioinformatic filters to provide relevance rank among the interactome proteins. We demonstrate the versatility of RRP to enable a systematic prioritization of the most relevant interaction partners from high content data, highlighted by the analysis of cancer relevant protein interactions for oncoproteins Pin1 and PME-1. We validated the importance of selected interactions by demonstration of PTOV1 and CSKN2B as novel regulators of Pin1 target c-Jun phosphorylation and reveal previously unknown interacting proteins that may mediate PME-1 effects via PP2A-inhibition. The RRP framework is modular and can be modified to answer versatile research problems depending on the nature of the biological question under study. Based on comparison of RRP to other existing filtering tools, the presented data indicate that RRP offers added value especially for the analysis of interacting proteins for which there is no sufficient prior knowledge available. Finally, we encourage the use of RRP in combination with either SAINT or CRAPome computational tools for selecting the candidate interactors that fulfill the both important requirements, functional relevance, and high confidence interaction detection. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical-biological defense remote sensing: what's happening

NASA Astrophysics Data System (ADS)

Carrico, John P.

1998-08-01

The proliferation of weapons of mass destruction (WMD) continues to be a serious threat to the security of the US. Proliferation of chemical and biological (CB) weapons is particularly disturbing, and the threats posed can be devastating. Critical elements of the US efforts to reduce and counter WMD proliferation include: (1) the location and characterization of WMD facilities and capabilities worldwide; (2) the ability to rapidly detect and identify the use of CB weapons for expeditious warning and reporting on the battlefield; and (3) the capability to mitigate deleterious consequences of a CB incident through effective protective and medical treatment measures. Remote sensing has been touted as a key technology in these efforts. Historically, the role of remote sensing in CB defense has been to provide early warning of an attack from an extended distance. However, additional roles for remote sensing in CB defense, as well as applications in related missions, are possible and should be pursued. This paper examines what has been happening in remote sensing over the past decade to address needs in this area. Accomplishments, emerging technologies, programmatic issues, and opportunities for the future are covered. The Department of Defence chemical- biological, the Department of Energy's Chemical Analysis by Laser Interrogation of Proliferation Effluents, and other agency related programs are examined. Also, the status of remote sensing in the commercial market arena for environmental monitoring, its relevance to the WMD counterproliferation program, and opportunities for technology transfer are discussed. A course of action for the future is recommended.

The neural optimal control hierarchy for motor control

NASA Astrophysics Data System (ADS)

DeWolf, T.; Eliasmith, C.

2011-10-01

Our empirical, neuroscientific understanding of biological motor systems has been rapidly growing in recent years. However, this understanding has not been systematically mapped to a quantitative characterization of motor control based in control theory. Here, we attempt to bridge this gap by describing the neural optimal control hierarchy (NOCH), which can serve as a foundation for biologically plausible models of neural motor control. The NOCH has been constructed by taking recent control theoretic models of motor control, analyzing the required processes, generating neurally plausible equivalent calculations and mapping them on to the neural structures that have been empirically identified to form the anatomical basis of motor control. We demonstrate the utility of the NOCH by constructing a simple model based on the identified principles and testing it in two ways. First, we perturb specific anatomical elements of the model and compare the resulting motor behavior with clinical data in which the corresponding area of the brain has been damaged. We show that damaging the assigned functions of the basal ganglia and cerebellum can cause the movement deficiencies seen in patients with Huntington's disease and cerebellar lesions. Second, we demonstrate that single spiking neuron data from our model's motor cortical areas explain major features of single-cell responses recorded from the same primate areas. We suggest that together these results show how NOCH-based models can be used to unify a broad range of data relevant to biological motor control in a quantitative, control theoretic framework.

Comparison of the protein-protein interfaces in the p53-DNA crystal structures: towards elucidation of the biological interface.

PubMed

Ma, Buyong; Pan, Yongping; Gunasekaran, K; Venkataraghavan, R Babu; Levine, Arnold J; Nussinov, Ruth

2005-03-15

p53, the tumor suppressor protein, functions as a dimer of dimers. However, how the tetramer binds to the DNA is still an open question. In the crystal structure, three copies of the p53 monomers (containing chains A, B, and C) were crystallized with the DNA-consensus element. Although the structure provides crucial data on the p53-DNA contacts, the active oligomeric state is unclear because the two dimeric (A-B and B-C) interfaces present in the crystal cannot both exist in the tetramer. Here, we address the question of which of these two dimeric interfaces may be more biologically relevant. We analyze the sequence and structural properties of the p53-p53 dimeric interfaces and carry out extensive molecular dynamics simulations of the crystal structures of the human and mouse p53 dimers. We find that the A-B interface residues are more conserved than those of the B-C. Molecular dynamics simulations show that the A-B interface can provide a stable DNA-binding motif in the dimeric state, unlike B-C. Our results indicate that the interface between chains A-B in the p53-DNA complex constitutes a better candidate for a stable biological interface, whereas the B-C interface is more likely to be due to crystal packing. Thus, they have significant implications toward our understanding of DNA binding by p53 as well as p53-mediated interactions with other proteins.

Why do we study animal toxins?

PubMed Central

ZHANG, Yun

2015-01-01

Venom (toxins) is an important trait evolved along the evolutionary tree of animals. Our knowledges on venoms, such as their origins and loss, the biological relevance and the coevolutionary patterns with other organisms are greatly helpful in understanding many fundamental biological questions, i.e., the environmental adaptation and survival competition, the evolution shaped development and balance of venoms, and the sophisticated correlations among venom, immunity, body power, intelligence, their genetic basis, inherent association, as well as the cost-benefit and trade-offs of biological economy. Lethal animal envenomation can be found worldwide. However, from foe to friend, toxin studies have led lots of important discoveries and exciting avenues in deciphering and fighting human diseases, including the works awarded the Nobel Prize and lots of key clinic therapeutics. According to our survey, so far, only less than 0.1% of the toxins of the venomous animals in China have been explored. We emphasize on the similarities shared by venom and immune systems, as well as the studies of toxin knowledge-based physiological toxin-like proteins/peptides (TLPs). We propose the natural pairing hypothesis. Evolution links toxins with humans. Our mission is to find out the right natural pairings and interactions of our body elements with toxins, and with endogenous toxin-like molecules. Although, in nature, toxins may endanger human lives, but from a philosophical point of view, knowing them well is an effective way to better understand ourselves. So, this is why we study toxins. PMID:26228472

Antidrug Antibody Formation in Oncology: Clinical Relevance and Challenges.

PubMed

van Brummelen, Emilie M J; Ros, Willeke; Wolbink, Gertjan; Beijnen, Jos H; Schellens, Jan H M

2016-10-01

: In oncology, an increasing number of targeted anticancer agents and immunotherapies are of biological origin. These biological drugs may trigger immune responses that lead to the formation of antidrug antibodies (ADAs). ADAs are directed against immunogenic parts of the drug and may affect efficacy and safety. In other medical fields, such as rheumatology and hematology, the relevance of ADA formation is well established. However, the relevance of ADAs in oncology is just starting to be recognized, and literature on this topic is scarce. In an attempt to fill this gap in the literature, we provide an up-to-date status of ADA formation in oncology. In this focused review, data on ADAs was extracted from 81 clinical trials with biological anticancer agents. We found that most biological anticancer drugs in these trials are immunogenic and induce ADAs (63%). However, it is difficult to establish the clinical relevance of these ADAs. In order to determine this relevance, the possible effects of ADAs on pharmacokinetics, efficacy, and safety parameters need to be investigated. Our data show that this was done in fewer than 50% of the trials. In addition, we describe the incidence and consequences of ADAs for registered agents. We highlight the challenges in ADA detection and argue for the importance of validating, standardizing, and describing well the used assays. Finally, we discuss prevention strategies such as immunosuppression and regimen adaptations. We encourage the launch of clinical trials that explore these strategies in oncology. Because of the increasing use of biologicals in oncology, many patients are at risk of developing antidrug antibodies (ADAs) during therapy. Although clinical consequences are uncertain, ADAs may affect pharmacokinetics, patient safety, and treatment efficacy. ADA detection and reporting is currently highly inconsistent, which makes it difficult to evaluate the clinical consequences. Standardized reporting of ADA investigations in the context of the aforementioned parameters is critical to understanding the relevance of ADA formation for each drug. Furthermore, the development of trials that specifically aim to investigate clinical prevention strategies in oncology is needed. ©AlphaMed Press.

Elemental content of Vietnamese rice. Part 2. Multivariate data analysis.

PubMed

Kokot, S; Phuong, T D

1999-04-01

Rice samples were obtained from the Red River region and some other parts of Vietnam as well as from Yanco, Australia. These samples were analysed for 14 elements (P, K, Mg, Ca, Mn, Zn, Fe, Cu, Al, Na, Ni, As, Mo and Cd) by ICP-AES, ICP-MS and FAAS as described in Part 1. This data matrix was then submitted to multivariate data analysis by principal component analysis to investigate the influences of environmental and crop cultivation variables on the elemental content of rice. Results revealed that geographical location, grain variety, seasons and soil conditions are the most likely significant factors causing changes in the elemental content between the rice samples. To assess rice quality according to its elemental content and physio-biological properties, a multicriteria decision making method (PROMETHEE) was applied. With the Vietnamese rice, the sticky rice appeared to contain somewhat higher levels of nutritionally significant elements such as P, K and Mg than the non-sticky rice. Also, rice samples grown during the wet season have better levels of nutritionally significant mineral elements than those of the dry season, but in general, the wet season seemed to provide better overall elemental and physio-biological rice quality.

Healthy Watersheds Protection

MedlinePlus

... chemical water quality conditions able to support healthy biological communities. Natural vegetative cover in the landscape, including ... habitat habitat A place where the physical and biological elements of ecosystems provide a suitable environment including ...

Environmental chemicals and breast cancer: An updated review of epidemiological literature informed by biological mechanisms.

PubMed

Rodgers, Kathryn M; Udesky, Julia O; Rudel, Ruthann A; Brody, Julia Green

2018-01-01

Many common environmental chemicals are mammary gland carcinogens in animal studies, activate relevant hormonal pathways, or enhance mammary gland susceptibility to carcinogenesis. Breast cancer's long latency and multifactorial etiology make evaluation of these chemicals in humans challenging. For chemicals previously identified as mammary gland toxicants, we evaluated epidemiologic studies published since our 2007 review. We assessed whether study designs captured relevant exposures and disease features suggested by toxicological and biological evidence of genotoxicity, endocrine disruption, tumor promotion, or disruption of mammary gland development. We systematically searched the PubMed database for articles with breast cancer outcomes published in 2006-2016 using terms for 134 environmental chemicals, sources, or biomarkers of exposure. We critically reviewed the articles. We identified 158 articles. Consistent with experimental evidence, a few key studies suggested higher risk for exposures during breast development to dichlorodiphenyltrichloroethane (DDT), dioxins, perfluorooctane-sulfonamide (PFOSA), and air pollution (risk estimates ranged from 2.14 to 5.0), and for occupational exposure to solvents and other mammary carcinogens, such as gasoline components (risk estimates ranged from 1.42 to 3.31). Notably, one 50-year cohort study captured exposure to DDT during several critical windows for breast development (in utero, adolescence, pregnancy) and when this chemical was still in use. Most other studies did not assess exposure during a biologically relevant window or specify the timing of exposure. Few studies considered genetic variation, but the Long Island Breast Cancer Study Project reported higher breast cancer risk for polycyclic aromatic hydrocarbons (PAHs) in women with certain genetic variations, especially in DNA repair genes. New studies that targeted toxicologically relevant chemicals and captured biological hypotheses about genetic variants or windows of breast susceptibility added to evidence of links between environmental chemicals and breast cancer. However, many biologically relevant chemicals, including current-use consumer product chemicals, have not been adequately studied in humans. Studies are challenged to reconstruct exposures that occurred decades before diagnosis or access biological samples stored that long. Other problems include measuring rapidly metabolized chemicals and evaluating exposure to mixtures. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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…

Can a Diversified Instructional Approach Featuring Active Learning Improve Biology Students' Attitudes toward General Education?

ERIC Educational Resources Information Center

Rutledge, Michael L.; Lampley, Sandra A.

2017-01-01

In an effort to make our classes more engaging, we recently reorganized sections of our nonmajors biology course, using current issues in biology and society as a premise to promote coherence among course content and emphasize the relevance of biological concepts to everyday life. A key aspect of the reorganization included the development and…

Out of place, out of mind: Schema-driven false memory effects for object-location bindings.

PubMed

Lew, Adina R; Howe, Mark L

2017-03-01

Events consist of diverse elements, each processed in specialized neocortical networks, with temporal lobe memory systems binding these elements to form coherent event memories. We provide a novel theoretical analysis of an unexplored consequence of the independence of memory systems for elements and their bindings, 1 that raises the paradoxical prediction that schema-driven false memories can act solely on the binding of event elements despite the superior retrieval of individual elements. This is because if 2, or more, schema-relevant elements are bound together in unexpected conjunctions, the unexpected conjunction will increase attention during encoding to both the elements and their bindings, but only the bindings will receive competition with evoked schema-expected bindings. We test our model by examining memory for object-location bindings in recognition (Study 1) and recall (Studies 2 and 3) tasks. After studying schema-relevant objects in unexpected locations (e.g., pan on a stool in a kitchen scene), participants who then viewed these objects in expected locations (e.g., pan on stove) at test were more likely to falsely remember this object-location pairing as correct, compared with participants that viewed a different unexpected object-location pairing (e.g., pan on floor). In recall, participants were more likely to correctly remember individual schema-relevant objects originally viewed in unexpected, as opposed to expected locations, but were then more likely to misplace these items in the original room scene to expected places, relative to control schema-irrelevant objects. Our theoretical analysis and novel paradigm provide a tool for investigating memory distortions acting on binding processes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Crossing Boundaries in Undergraduate Biology Education

ERIC Educational Resources Information Center

Vanderklein, Dirk; Munakata, Mika; McManus, Jason

2016-01-01

In an effort to make mathematics relevant to biology students, the authors developed two modules that sought to integrate mathematics and ecology instruction to differing degrees. The modules were developed by a team of biology and mathematics educators and were implemented in an ecology course using three different instructional methods for three…

Linking School Biology and Community in Developing Countries.

ERIC Educational Resources Information Center

Knamiller, Gary W.

1984-01-01

Explores the role of biological education in placing the school in its own local community and the real social-economic environment that surrounds it. Particular reference is made to issue-based biological education in schools as an attempt to bridge the gap between purely academic schooling and education for relevance. (Author)

Multiscale smeared finite element model for mass transport in biological tissue: From blood vessels to cells and cellular organelles.

PubMed

Kojic, M; Milosevic, M; Simic, V; Koay, E J; Kojic, N; Ziemys, A; Ferrari, M

2018-05-21

One of the basic and vital processes in living organisms is mass exchange, which occurs on several levels: it goes from blood vessels to cells and organelles within cells. On that path, molecules, as oxygen, metabolic products, drugs, etc. Traverse different macro and micro environments - blood, extracellular/intracellular space, and interior of organelles; and also biological barriers such as walls of blood vessels and membranes of cells and organelles. Many aspects of this mass transport remain unknown, particularly the biophysical mechanisms governing drug delivery. The main research approach relies on laboratory and clinical investigations. In parallel, considerable efforts have been directed to develop computational tools for additional insight into the intricate process of mass exchange and transport. Along these lines, we have recently formulated a composite smeared finite element (CSFE) which is composed of the smeared continuum pressure and concentration fields of the capillary and lymphatic system, and of these fields within tissue. The element offers an elegant and simple procedure which opens up new lines of inquiry and can be applied to large systems such as organs and tumors models. Here, we extend this concept to a multiscale scheme which concurrently couples domains that span from large blood vessels, capillaries and lymph, to cell cytosol and further to organelles of nanometer size. These spatial physical domains are coupled by the appropriate connectivity elements representing biological barriers. The composite finite element has "degrees of freedom" which include pressures and concentrations of all compartments of the vessels-tissue assemblage. The overall model uses the standard, measurable material properties of the continuum biological environments and biological barriers. It can be considered as a framework into which we can incorporate various additional effects (such as electrical or biochemical) for transport through membranes or within cells. This concept and the developed FE software within our package PAK offers a computational tool that can be applied to whole-organ systems, while also including specific domains such as tumors. The solved examples demonstrate the accuracy of this model and its applicability to large biological systems. Copyright © 2018. Published by Elsevier Ltd.

Classifying Life, Reconstructing History and Teaching Diversity: Philosophical Issues in the Teaching of Biological Systematics and Biodiversity

ERIC Educational Resources Information Center

Reydon, Thomas A. C.

2013-01-01

Classification is a central endeavor in every scientific field of work. Classification in biology, however, is distinct from classification in other fields of science in a number of ways. Thus, understanding how biological classification works is an important element in understanding the nature of biological science. In the present paper, I…

COPS: Detecting Co-Occurrence and Spatial Arrangement of Transcription Factor Binding Motifs in Genome-Wide Datasets

PubMed Central

Lohmann, Ingrid

2012-01-01

In multi-cellular organisms, spatiotemporal activity of cis-regulatory DNA elements depends on their occupancy by different transcription factors (TFs). In recent years, genome-wide ChIP-on-Chip, ChIP-Seq and DamID assays have been extensively used to unravel the combinatorial interaction of TFs with cis-regulatory modules (CRMs) in the genome. Even though genome-wide binding profiles are increasingly becoming available for different TFs, single TF binding profiles are in most cases not sufficient for dissecting complex regulatory networks. Thus, potent computational tools detecting statistically significant and biologically relevant TF-motif co-occurrences in genome-wide datasets are essential for analyzing context-dependent transcriptional regulation. We have developed COPS (Co-Occurrence Pattern Search), a new bioinformatics tool based on a combination of association rules and Markov chain models, which detects co-occurring TF binding sites (BSs) on genomic regions of interest. COPS scans DNA sequences for frequent motif patterns using a Frequent-Pattern tree based data mining approach, which allows efficient performance of the software with respect to both data structure and implementation speed, in particular when mining large datasets. Since transcriptional gene regulation very often relies on the formation of regulatory protein complexes mediated by closely adjoining TF binding sites on CRMs, COPS additionally detects preferred short distance between co-occurring TF motifs. The performance of our software with respect to biological significance was evaluated using three published datasets containing genomic regions that are independently bound by several TFs involved in a defined biological process. In sum, COPS is a fast, efficient and user-friendly tool mining statistically and biologically significant TFBS co-occurrences and therefore allows the identification of TFs that combinatorially regulate gene expression. PMID:23272209

Biological cell as a soft magnetoelectric material: Elucidating the physical mechanisms underpinning the detection of magnetic fields by animals

NASA Astrophysics Data System (ADS)

Krichen, S.; Liu, L.; Sharma, P.

2017-10-01

Sharks, birds, bats, turtles, and many other animals can detect magnetic fields. Aside from using this remarkable ability to exploit the terrestrial magnetic field map to sense direction, a subset is also able to implement a version of the so-called geophysical positioning system. How do these animals detect magnetic fields? The answer to this rather deceptively simple question has proven to be quite elusive. The currently prevalent theories, while providing interesting insights, fall short of explaining several aspects of magnetoreception. For example, minute magnetic particles have been detected in magnetically sensitive animals. However, how is the detected magnetic field converted into electrical signals given any lack of experimental evidence for relevant electroreceptors? In principle, a magnetoelectric material is capable of converting magnetic signals into electricity (and vice versa). This property, however, is rare and restricted to a rather small set of exotic hard crystalline materials. Indeed, such elements have never been detected in the animals studied so far. In this work we quantitatively outline the conditions under which a biological cell may detect a magnetic field and convert it into electrical signals detectable by biological cells. Specifically, we prove the existence of an overlooked strain-mediated mechanism and show that most biological cells can act as nontrivial magnetoelectric materials provided that the magnetic permeability constant is only slightly more than that of a vacuum. The enhanced magnetic permeability is easily achieved by small amounts of magnetic particles that have been experimentally detected in magnetosensitive animals. Our proposed mechanism appears to explain most of the experimental observations related to the physical basis of magnetoreception.

Copper Capture in a Thioether-Functionalized Porous Polymer Applied to the Detection of Wilson’s Disease

PubMed Central

2016-01-01

Copper is an essential nutrient for life, but at the same time, hyperaccumulation of this redox-active metal in biological fluids and tissues is a hallmark of pathologies such as Wilson’s and Menkes diseases, various neurodegenerative diseases, and toxic environmental exposure. Diseases characterized by copper hyperaccumulation are currently challenging to identify due to costly diagnostic tools that involve extensive technical workup. Motivated to create simple yet highly selective and sensitive diagnostic tools, we have initiated a program to develop new materials that can enable monitoring of copper levels in biological fluid samples without complex and expensive instrumentation. Herein, we report the design, synthesis, and properties of PAF-1-SMe, a robust three-dimensional porous aromatic framework (PAF) densely functionalized with thioether groups for selective capture and concentration of copper from biofluids as well as aqueous samples. PAF-1-SMe exhibits a high selectivity for copper over other biologically relevant metals, with a saturation capacity reaching over 600 mg/g. Moreover, the combination of PAF-1-SMe as a material for capture and concentration of copper from biological samples with 8-hydroxyquinoline as a colorimetric indicator affords a method for identifying aberrant elevations of copper in urine samples from mice with Wilson’s disease and also tracing exogenously added copper in serum. This divide-and-conquer sensing strategy, where functional and robust porous materials serve as molecular recognition elements that can be used to capture and concentrate analytes in conjunction with molecular indicators for signal readouts, establishes a valuable starting point for the use of porous polymeric materials in noninvasive diagnostic applications. PMID:27285482

Enhanced Bone Formation in Segmental Defects with BMP2 in a Biologically Relevant Molecular Context

DTIC Science & Technology

2016-10-16

gun shots . These do not heal on their own once a ‘critical size’ segment of bone is missing. One strategy to induce healing is to use bone-inducing...accelerate BMP2-induced bone formation by presenting the growth factor in a more biologically relevant context. This is based on our observation...that manganese increases the binding of BMP2 to COMP. The next steps are to validate these observations using BMP2:COMP on HA/PLG scaffolds in-vitro

Linking field-based metabolomics and chemical analyses to prioritize contaminants of emerging concern in the Great Lakes basin

USGS Publications Warehouse

Davis, John M.; Ekman, Drew R.; Teng, Quincy; Ankley, Gerald T.; Berninger, Jason P.; Cavallin, Jenna E.; Jensen, Kathleen M.; Kahl, Michael D.; Schroeder, Anthony L.; Villeneuve, Daniel L.; Jorgenson, Zachary G.; Lee, Kathy E.; Collette, Timothy W.

2016-01-01

The ability to focus on the most biologically relevant contaminants affecting aquatic ecosystems can be challenging because toxicity-assessment programs have not kept pace with the growing number of contaminants requiring testing. Because it has proven effective at assessing the biological impacts of potentially toxic contaminants, profiling of endogenous metabolites (metabolomics) may help screen out contaminants with a lower likelihood of eliciting biological impacts, thereby prioritizing the most biologically important contaminants. The authors present results from a study that utilized cage-deployed fathead minnows (Pimephales promelas) at 18 sites across the Great Lakes basin. They measured water temperature and contaminant concentrations in water samples (132 contaminants targeted, 86 detected) and used 1H-nuclear magnetic resonance spectroscopy to measure endogenous metabolites in polar extracts of livers. They used partial least-squares regression to compare relative abundances of endogenous metabolites with contaminant concentrations and temperature. The results indicated that profiles of endogenous polar metabolites covaried with at most 49 contaminants. The authors identified up to 52% of detected contaminants as not significantly covarying with changes in endogenous metabolites, suggesting they likely were not eliciting measurable impacts at these sites. This represents a first step in screening for the biological relevance of detected contaminants by shortening lists of contaminants potentially affecting these sites. Such information may allow risk assessors to prioritize contaminants and focus toxicity testing on the most biologically relevant contaminants. Environ Toxicol Chem 2016;35:2493–2502.

Revisiting the continuum model of tendon pathology: what is its merit in clinical practice and research?

PubMed Central

Cook, J L; Rio, E; Purdam, C R; Docking, S I

2016-01-01

The pathogenesis of tendinopathy and the primary biological change in the tendon that precipitates pathology have generated several pathoaetiological models in the literature. The continuum model of tendon pathology, proposed in 2009, synthesised clinical and laboratory-based research to guide treatment choices for the clinical presentations of tendinopathy. While the continuum has been cited extensively in the literature, its clinical utility has yet to be fully elucidated. The continuum model proposed a model for staging tendinopathy based on the changes and distribution of disorganisation within the tendon. However, classifying tendinopathy based on structure in what is primarily a pain condition has been challenged. The interplay between structure, pain and function is not yet fully understood, which has partly contributed to the complex clinical picture of tendinopathy. Here we revisit and assess the merit of the continuum model in the context of new evidence. We (1) summarise new evidence in tendinopathy research in the context of the continuum, (2) discuss tendon pain and the relevance of a model based on structure and (3) describe relevant clinical elements (pain, function and structure) to begin to build a better understanding of the condition. Our goal is that the continuum model may help guide targeted treatments and improved patient outcomes. PMID:27127294

Epigenetics: a new frontier in dentistry.

PubMed

Williams, S D; Hughes, T E; Adler, C J; Brook, A H; Townsend, G C

2014-06-01

In 2007, only four years after the completion of the Human Genome Project, the journal Science announced that epigenetics was the 'breakthrough of the year'. Time magazine placed it second in the top 10 discoveries of 2009. While our genetic code (i.e. our DNA) contains all of the information to produce the elements we require to function, our epigenetic code determines when and where genes in the genetic code are expressed. Without the epigenetic code, the genetic code is like an orchestra without a conductor. Although there is now a substantial amount of published research on epigenetics in medicine and biology, epigenetics in dental research is in its infancy. However, epigenetics promises to become increasingly relevant to dentistry because of the role it plays in gene expression during development and subsequently potentially influencing oral disease susceptibility. This paper provides a review of the field of epigenetics aimed specifically at oral health professionals. It defines epigenetics, addresses the underlying concepts and provides details about specific epigenetic molecular mechanisms. Further, we discuss some of the key areas where epigenetics is implicated, and review the literature on epigenetics research in dentistry, including its relevance to clinical disciplines. This review considers some implications of epigenetics for the future of dental practice, including a 'personalized medicine' approach to the management of common oral diseases. © 2014 Australian Dental Association.

Stochastic theory of photon flow in homogeneous and heterogeneous anisotropic biological and artificial material

NASA Astrophysics Data System (ADS)

Miller, Steven D.

1995-05-01

Standard Monte Carlo methods used in photon diffusion score absorbed photons or statistical weight deposited within voxels comprising a mesh. An alternative approach to a stochastic description is considered for rapid surface flux calculations and finite medias. Matrix elements are assigned to a spatial lattice whose function is to score vector intersections of scattered photons making transitions into either the forward or back solid angle half spaces. These complete matrix elements can be related to the directional fluxes within the lattice space. This model differentiates between ballistic, quasi-ballistic, and highly diffuse photon contributions, and effectively models the subsurface generation of a scattered light flux from a ballistic source. The connection between a path integral and diffusion is illustrated. Flux perturbations can be effectively illustrated for tissue-tumor-tissue and for 3 layer systems with strong absorption in one or more layers. For conditions where the diffusion theory has difficulties such as strong absorption, highly collimated sources, small finite volumes, and subsurface regions, the computation time of the algorithm is rapid with good accuracy and compliments other description of photon diffusion. The model has the potential to do computations relevant to photodynamic therapy (PDT) and analysis of laser beam interaction with tissues.

Ecological quality boundary-setting procedures: the Gulf of Riga case study.

PubMed

Aigars, Juris; Müller-Karulis, Bärbel; Martin, Georg; Jermakovs, Vadims

2008-03-01

Two approaches for setting ecological class boundaries, response curves and a simplified mathematical boundary-setting protocol, were tested for coastal, transitional and open waters in the Gulf of Riga, Baltic Sea. The simplified mathematical boundary-setting protocol defines acceptable ecological status based on expert judgment by a uniform relative deviation from reference conditions. In contrast, response curves derive class boundary definitions from observed changes in biological quality elements along environmental pressure gradients for class boundary definitions. Identification of relevant environmental pressures for the construction of response curves was based on a conceptual model of eutrophication in the Gulf of Riga. Response curves were successfully established for summer chlorophyll a and transparency, as well as for macrozoobenthos abundance in the Central Gulf, macrozoobenthos biotic coefficient in the Southern Gulf, and maximum depth of phytobenthos in the Northern Gulf. In the Gulf of Riga response curves almost always permitted a larger deviation from reference conditions than the 50% deviation applied for the simplified mathematical boundary-setting protocol. The case study clearly demonstrated that class boundary definitions should take into account the sensitivity of the target water body. Also, the class boundaries for different ecological quality elements were internally more consistent than those derived by the simplified mathematical boundary-setting protocol.

GREGOR: evaluating global enrichment of trait-associated variants in epigenomic features using a systematic, data-driven approach.

PubMed

Schmidt, Ellen M; Zhang, Ji; Zhou, Wei; Chen, Jin; Mohlke, Karen L; Chen, Y Eugene; Willer, Cristen J

2015-08-15

The majority of variation identified by genome wide association studies falls in non-coding genomic regions and is hypothesized to impact regulatory elements that modulate gene expression. Here we present a statistically rigorous software tool GREGOR (Genomic Regulatory Elements and Gwas Overlap algoRithm) for evaluating enrichment of any set of genetic variants with any set of regulatory features. Using variants from five phenotypes, we describe a data-driven approach to determine the tissue and cell types most relevant to a trait of interest and to identify the subset of regulatory features likely impacted by these variants. Last, we experimentally evaluate six predicted functional variants at six lipid-associated loci and demonstrate significant evidence for allele-specific impact on expression levels. GREGOR systematically evaluates enrichment of genetic variation with the vast collection of regulatory data available to explore novel biological mechanisms of disease and guide us toward the functional variant at trait-associated loci. GREGOR, including source code, documentation, examples, and executables, is available at http://genome.sph.umich.edu/wiki/GREGOR. cristen@umich.edu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Assessment of chemicals released in the marine environment by dielectric elastomers useful as active elements in wave energy harvesters.

PubMed

Zaltariov, Mirela-Fernanda; Bele, Adrian; Vasiliu, Lavinia; Gradinaru, Luiza; Vornicu, Nicoleta; Racles, Carmen; Cazacu, Maria

2018-01-05

A series of elastomers, either natural or synthetic (some of them commercial, while others prepared in the laboratory), suitable for use as active elements in devices for wave energy harvesting, were evaluated concerning their behavior and effects on the marine environment. In this aim, the elastomer films, initially evaluated regarding their aspect, structure, surface wettability, and tolerance of microorganisms growth, were immersed in synthetic seawater (SSW) within six months for assessing compounds released. There were analyzed the changes occurred both in the elastomers and salt water in which they were immersed. For this, water samples taken at set time intervals were analyzed by using a sequence of sensitive spectral techniques: UV-vis, IR, and in relevant cases 1 H NMR and electrospray ionization mass spectrometry (ESI-MS), able to detect and identify organic compounds, while after six months, they were also investigated from the point of view of aspect, presence of metal traces, pH, and biological activity. The changes in aspect, structure and morphology of the dielectric films at the end of the dipping period were also evaluated by visual inspection, IR spectroscopy by using spectral subtraction method, and SEM-EDX technique. Copyright © 2017 Elsevier B.V. All rights reserved.

Evolutionary characterization of Ty3/gypsy-like LTR retrotransposons in the parasitic cestode Echinococcus granulosus.

PubMed

Bae, Young-An

2016-11-01

Cyclophyllidean cestodes including Echinococcus granulosus have a smaller genome and show characteristics such as loss of the gut, a segmented body plan, and accelerated growth rate in hosts compared with other tissue-invading helminths. In an effort to address the molecular mechanism relevant to genome shrinkage, the evolutionary status of long-terminal-repeat (LTR) retrotransposons, which are known as the most potent genomic modulators, was investigated in the E. granulosus draft genome. A majority of the E. granulosus LTR retrotransposons were classified into a novel characteristic clade, named Saci-2, of the Ty3/gypsy family, while the remaining elements belonged to the CsRn1 clade of identical family. Their nucleotide sequences were heavily corrupted by frequent base substitutions and segmental losses. The ceased mobile activity of the major retrotransposons and the following intrinsic DNA loss in their inactive progenies might have contributed to decrease in genome size. Apart from the degenerate copies, a gag gene originating from a CsRn1-like element exhibited substantial evidences suggesting its domestication including a preserved coding profile and transcriptional activity, the presence of syntenic orthologues in cestodes, and selective pressure acting on the gene. To my knowledge, the endogenized gag gene is reported for the first time in invertebrates, though its biological function remains elusive.

FEBio: finite elements for biomechanics.

PubMed

Maas, Steve A; Ellis, Benjamin J; Ateshian, Gerard A; Weiss, Jeffrey A

2012-01-01

In the field of computational biomechanics, investigators have primarily used commercial software that is neither geared toward biological applications nor sufficiently flexible to follow the latest developments in the field. This lack of a tailored software environment has hampered research progress, as well as dissemination of models and results. To address these issues, we developed the FEBio software suite (http://mrl.sci.utah.edu/software/febio), a nonlinear implicit finite element (FE) framework, designed specifically for analysis in computational solid biomechanics. This paper provides an overview of the theoretical basis of FEBio and its main features. FEBio offers modeling scenarios, constitutive models, and boundary conditions, which are relevant to numerous applications in biomechanics. The open-source FEBio software is written in C++, with particular attention to scalar and parallel performance on modern computer architectures. Software verification is a large part of the development and maintenance of FEBio, and to demonstrate the general approach, the description and results of several problems from the FEBio Verification Suite are presented and compared to analytical solutions or results from other established and verified FE codes. An additional simulation is described that illustrates the application of FEBio to a research problem in biomechanics. Together with the pre- and postprocessing software PREVIEW and POSTVIEW, FEBio provides a tailored solution for research and development in computational biomechanics.

A finite elements method to solve the Bloch–Torrey equation applied to diffusion magnetic resonance imaging

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

Nguyen, Dang Van; NeuroSpin, Bat145, Point Courrier 156, CEA Saclay Center, 91191 Gif-sur-Yvette Cedex; Li, Jing-Rebecca, E-mail: jingrebecca.li@inria.fr

2014-04-15

The complex transverse water proton magnetization subject to diffusion-encoding magnetic field gradient pulses in a heterogeneous medium can be modeled by the multiple compartment Bloch–Torrey partial differential equation (PDE). In addition, steady-state Laplace PDEs can be formulated to produce the homogenized diffusion tensor that describes the diffusion characteristics of the medium in the long time limit. In spatial domains that model biological tissues at the cellular level, these two types of PDEs have to be completed with permeability conditions on the cellular interfaces. To solve these PDEs, we implemented a finite elements method that allows jumps in the solution atmore » the cell interfaces by using double nodes. Using a transformation of the Bloch–Torrey PDE we reduced oscillations in the searched-for solution and simplified the implementation of the boundary conditions. The spatial discretization was then coupled to the adaptive explicit Runge–Kutta–Chebyshev time-stepping method. Our proposed method is second order accurate in space and second order accurate in time. We implemented this method on the FEniCS C++ platform and show time and spatial convergence results. Finally, this method is applied to study some relevant questions in diffusion MRI.« less

Potential health and environmental effects of trace elements and radionuclides from increased coal utilization.

PubMed Central

Van Hook, R I

1979-01-01

This report addresses the effects of coal-derived trace and radioactive elements. A summary of our current understanding of health and environmental effects of trace and radioactive elements released during coal mining, cleaning, combustion, and ash disposal is presented. Physical and biological transport phenomena which are important in determining organism exposure are also discussed. Biological concentration and transformation as well as synergistic and antagonistic actions among trace contaminants are discussed in terms of their importance in mobility, persistence, availability, and ultimate toxicity. The consequences of implementing the President's National Energy Plan are considered in terms of the impact of the NEP in 1985 and 2000 on the potential effects of trace and radioactive elements from the coal fuel cycle. Areas of needed research are identified in specific recommendations. PMID:540619

Two-Element Transducer for Ultrasound

NASA Technical Reports Server (NTRS)

Lecroissette, D. H.; Heyser, R. C.

1986-01-01

Separation of transmitting and receiving units improves probing of deep tissue. Ultrasonic transducer has dual elements to increase depth at which sonic images are made of biological tissue. Transducer uses separate transmitting and receiving elements, and frequency response of receiving element independently designed to accommodate attenuation of higher frequencies by tissue. New transducer intended for pulse-echo ultrasonic systems in which reflected sound pulses reveal features in tissue.

A Unifying Review of Bioassay-Guided Fractionation, Effect-Directed Analysis and Related Techniques

PubMed Central

Weller, Michael G.

2012-01-01

The success of modern methods in analytical chemistry sometimes obscures the problem that the ever increasing amount of analytical data does not necessarily give more insight of practical relevance. As alternative approaches, toxicity- and bioactivity-based assays can deliver valuable information about biological effects of complex materials in humans, other species or even ecosystems. However, the observed effects often cannot be clearly assigned to specific chemical compounds. In these cases, the establishment of an unambiguous cause-effect relationship is not possible. Effect-directed analysis tries to interconnect instrumental analytical techniques with a biological/biochemical entity, which identifies or isolates substances of biological relevance. Successful application has been demonstrated in many fields, either as proof-of-principle studies or even for complex samples. This review discusses the different approaches, advantages and limitations and finally shows some practical examples. The broad emergence of effect-directed analytical concepts might lead to a true paradigm shift in analytical chemistry, away from ever growing lists of chemical compounds. The connection of biological effects with the identification and quantification of molecular entities leads to relevant answers to many real life questions. PMID:23012539

Bioinspired design and interfacial failure of biomedical systems

NASA Astrophysics Data System (ADS)

Rahbar, Nima

The deformation mechanism of nacre as a model biological material is studied in this project. A numerical model is presented which consists of tensile pillars, shear pillars, asperities and aragonite platelets. It has been shown that the tensile pillars are the main elements that control the global stiffness of the nacre structure. Meanwhile, ultimate strength of the nacre structure is controlled by asperities and their behavior and the ratio of L/2D which is itself a function of the geometry of the platelets. Protein/shear pillars provide the glue which holds the assembly of entire system together, particularly in the direction normal to the platelets main axis. This dissertation also presents the results of a combined theoretical/computational and experimental effort to develop crack resistant dental multilayers that are inspired by the functionally graded dento-enamel junction (DEJ) structure that occurs between dentin and enamel in natural teeth. The complex structures of natural teeth and ceramic crowns are idealized using at layered configurations. The potential effects of occlusal contact are then modeled using finite element simulations of Hertzian contact. The resulting stress distributions are compared for a range of possible bioinspired, functionally graded architecture. The computed stress distributions show that the highest stress concentrations in the top ceramic layer of crown structures are reduced significantly by the use of bioinspired functionally graded architectures. The reduced stresses are shown to be associated with significant improvements (30%) in the pop-in loads over a wide range of clinically-relevant loading rates. The implications of the results are discussed for the design of bioinspired dental ceramic crown structures. The results of a combined experimental and computational study of mixed mode fracture in glass/cement and zirconia/cement interfaces that are relevant to dental restorations is also presented. The interfacial fracture is investigated using Brazil-nut specimens. The kinking in-and-out of the interface that occurs between glass/cement and zirconia/cement interfaces, is also shown to be consistent with predictions from a microstructure-based finite element model. The predictions are later verified using focused ion beam and scanning electron microscopy images. Finally, the adhesion between layers that are relevant to drug-eluting stents is explored. Brazil disk specimens were used to measure the interfacial fracture energies between the layers of a model drug eluting stent over a wide range of mode mixities. The trends in the overall fracture energies are predicted using a combination of adhesion theories and fracture mechanics concepts. The measured interfacial fracture energies are shown to be in good agreement with the predictions.

Diversification and enrichment of clinical biomaterials inspired by Darwinian evolution.

PubMed

Green, D W; Watson, G S; Watson, J A; Lee, D-J; Lee, J-M; Jung, H-S

2016-09-15

Regenerative medicine and biomaterials design are driven by biomimicry. There is the essential requirement to emulate human cell, tissue, organ and physiological complexity to ensure long-lasting clinical success. Biomimicry projects for biomaterials innovation can be re-invigorated with evolutionary insights and perspectives, since Darwinian evolution is the original dynamic process for biological organisation and complexity. Many existing human inspired regenerative biomaterials (defined as a nature generated, nature derived and nature mimicking structure, produced within a biological system, which can deputise for, or replace human tissues for which it closely matches) are without important elements of biological complexity such as, hierarchy and autonomous actions. It is possible to engineer these essential elements into clinical biomaterials via bioinspired implementation of concepts, processes and mechanisms played out during Darwinian evolution; mechanisms such as, directed, computational, accelerated evolutions and artificial selection contrived in the laboratory. These dynamos for innovation can be used during biomaterials fabrication, but also to choose optimal designs in the regeneration process. Further evolutionary information can help at the design stage; gleaned from the historical evolution of material adaptations compared across phylogenies to changes in their environment and habitats. Taken together, harnessing evolutionary mechanisms and evolutionary pathways, leading to ideal adaptations, will eventually provide a new class of Darwinian and evolutionary biomaterials. This will provide bioengineers with a more diversified and more efficient innovation tool for biomaterial design, synthesis and function than currently achieved with synthetic materials chemistry programmes and rational based materials design approach, which require reasoned logic. It will also inject further creativity, diversity and richness into the biomedical technologies that we make. All of which are based on biological principles. Such evolution-inspired biomaterials have the potential to generate innovative solutions, which match with existing bioengineering problems, in vital areas of clinical materials translation that include tissue engineering, gene delivery, drug delivery, immunity modulation, and scar-less wound healing. Evolution by natural selection is a powerful generator of innovations in molecular, materials and structures. Man has influenced evolution for thousands of years, to create new breeds of farm animals and crop plants, but now molecular and materials can be molded in the same way. Biological molecules and simple structures can be evolved, literally in the laboratory. Furthermore, they are re-designed via lessons learnt from evolutionary history. Through a 3-step process to (1) create variants in material building blocks, (2) screen the variants with beneficial traits/properties and (3) select and support their self-assembly into usable materials, improvements in design and performance can emerge. By introducing biological molecules and small organisms into this process, it is possible to make increasingly diversified, sophisticated and clinically relevant materials for multiple roles in biomedicine. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Photonic structures in biology

NASA Astrophysics Data System (ADS)

Vukusic, Pete; Sambles, J. Roy

2003-08-01

Millions of years before we began to manipulate the flow of light using synthetic structures, biological systems were using nanometre-scale architectures to produce striking optical effects. An astonishing variety of natural photonic structures exists: a species of Brittlestar uses photonic elements composed of calcite to collect light, Morpho butterflies use multiple layers of cuticle and air to produce their striking blue colour and some insects use arrays of elements, known as nipple arrays, to reduce reflectivity in their compound eyes. Natural photonic structures are providing inspiration for technological applications.

Dual fiber microprobe for mapping elemental distributions in biological cells

DOEpatents

Martin, Rodger C [Powell, TN; Martin, Madhavi Z [Powell, TN

2007-07-31

Laser-induced breakdown spectroscopy (LIBS) is applied on a microscale for in situ elemental analysis and spatial mapping in biological cells. A high power laser beam is focused onto a cell surface using a dual branching optical fiber probe for optical excitation of the cell constituents. Dual spectrometers and ICCD detectors capture the emission spectra from the excited cell(s). Repeated probing or repositioning of the laser beam with respect to the cell can provide 2-D or 3-D mapping of the cell.

Biological Effects of Laser Radiation. Volume I. Review of the Literature on Biological Effects of Laser Radiation-to 1965.

DTIC Science & Technology

1978-10-17

because of the rapid progress made in laser technology to date. The use of the Laser Microprobe in spectrochemical analysis of the elements is based on...spectroscopy to vaporize microscopic amounts of samples for elemental analysis . On the other hand, the intense, highly monochromatic laser beam is being...employed as a light source for Raman spectroscopy to study molecular structure. These two uses of lasers in spectroscopic analysis have been sucessful

Optical fiber-based biosensors.

PubMed

Monk, David J; Walt, David R

2004-08-01

This review outlines optical fiber-based biosensor research from January 2001 through September 2003 and was written to complement the previous review in this journal by Marazuela and Moreno-Bondi. Optical fiber-based biosensors combine the use of a biological recognition element with an optical fiber or optical fiber bundle. They are classified by the nature of the biological recognition element used for sensing: enzyme, antibody/antigen (immunoassay), nucleic acid, whole cell, and biomimetic, and may be used for a variety of analytes ranging from metals and chemicals to physiological materials.

G Quadruplex in Plants: A Ubiquitous Regulatory Element and Its Biological Relevance.

PubMed

Yadav, Vikas; Hemansi; Kim, Nayun; Tuteja, Narendra; Yadav, Puja

2017-01-01

G quadruplexes (G4) are higher-order DNA and RNA secondary structures formed by G-rich sequences that are built around tetrads of hydrogen-bonded guanine bases. Potential G4 quadruplex sequences have been identified in G-rich eukaryotic non-telomeric and telomeric genomic regions. Upon function, G4 formation is known to involve in chromatin remodeling, gene regulation and has been associated with genomic instability, genetic diseases and cancer progression. The natural role and biological validation of G4 structures is starting to be explored, and is of particular interest for the therapeutic interventions for human diseases. However, the existence and physiological role of G4 DNA and G4 RNA in plants species have not been much investigated yet and therefore, is of great interest for the development of improved crop varieties for sustainable agriculture. In this context, several recent studies suggests that these highly diverse G4 structures in plants can be employed to regulate expression of genes involved in several pathophysiological conditions including stress response to biotic and abiotic stresses as well as DNA damage. In the current review, we summarize the recent findings regarding the emerging functional significance of G4 structures in plants and discuss their potential value in the development of improved crop varieties.

A highly sensitive and selective fluorescent sensor for detection of sulfide anion based on the steric hindrance effect

NASA Astrophysics Data System (ADS)

Chen, Guanfan; Tang, Mengzhuo; Fu, Xiufang; Cheng, Fenmin; Zou, Xianghua; Wang, Jingpei; Zeng, Rongjin

2018-01-01

Sulfide anions are not only generated as a byproduct from industrial processes but also as a crucial kind of element in biological systems. Therefore, fluorescent probes for detecting sulfide anion with sensitive and selective characters are highly popular. In this study, we report a highly sensitive and selective fluorescent sensor M1 for detection of sulfide anion based on the steric hindrance effect, where the recognition unit, dinitrobenzenesulfonate ester group is linked to aromatic ortho-position in the porphyrin, and correspondingly the fluorescence of fluorescein is efficiently quenched. Compared with the sensors with recognition unit linked to the other aromatic positions, the fluorescent sensor M1 has a lower fluorescence background. Furthermore, the corresponding fluorescence responses (F/F0) of M1 for mercapto amino-acid GSH, Hcy and Cys, were all far lower than the relative fluorescence ratio F/F0 values for S2-. It means that M1 is sensitive and selective to detection of S2-, and has an anti-disturbance ability to the biologically-relevant thiols, GSH, Hcy and Cys, and has the prospect of application in the exact detection of sulfide anions in living organisms. This approach offers some useful insights for realizing sensitive and selective fluorescent turn-on sensing in the detection assays for other analytes.

Lithium/aluminium alloys. A problem material for biological monitoring.

PubMed

Bencze, K; Pelikan, C; Bahemann-Hoffmeister, A; Kronseder, A

1991-01-01

Investigations on aqueous and nonaqueous media have shown that the dust particles of lithium/aluminium alloy are readily soluble in blood serum. Concentration of 10 mg A1 and 3 mg Li in 1 l serum constitute the saturation values in human blood serum at 20 degrees C. Further observations are intended to clarify the danger at the workplace. With a short-term exposure, the change in concentration of Li and Al was followed in the working environment and in the staff. Both elements (Li and Al) were determined in the working air, in the urine, the blood serum and on human skin with electrothermal AAS. On human skin, microerosions arise owing to hydrolytic destruction of the epidermis after long-term contact. The intensive irritant action of Li/Al dust is most relevant for preventive measures. It must also be considered that the Al values in the blood serum are raised by up to 50% in the presence of Li. The resorption and/or the bioavailability of Al is altered by Li. In the presence of Li up to a Li content of 2.5% in Al dust, a MAK (biological tolerance value, threshold limit value) of 1 mg Al/m3 room air (for the total dust) is recommended.

Acoustic fine structure may encode biologically relevant information for zebra finches.

PubMed

Prior, Nora H; Smith, Edward; Lawson, Shelby; Ball, Gregory F; Dooling, Robert J

2018-04-18

The ability to discriminate changes in the fine structure of complex sounds is well developed in birds. However, the precise limit of this discrimination ability and how it is used in the context of natural communication remains unclear. Here we describe natural variability in acoustic fine structure of male and female zebra finch calls. Results from psychoacoustic experiments demonstrate that zebra finches are able to discriminate extremely small differences in fine structure, which are on the order of the variation in acoustic fine structure that is present in their vocal signals. Results from signal analysis methods also suggest that acoustic fine structure may carry information that distinguishes between biologically relevant categories including sex, call type and individual identity. Combined, our results are consistent with the hypothesis that zebra finches can encode biologically relevant information within the fine structure of their calls. This study provides a foundation for our understanding of how acoustic fine structure may be involved in animal communication.

Sex and gonadal hormones in mouse models of Alzheimer’s disease: what is relevant to the human condition?

PubMed Central

2012-01-01

Biologic sex and gonadal hormones matter in human aging and diseases of aging such as Alzheimer’s – and the importance of studying their influences relates directly to human health. The goal of this article is to review the literature to date on sex and hormones in mouse models of Alzheimer’s disease (AD) with an exclusive focus on interpreting the relevance of findings to the human condition. To this end, we highlight advances in AD and in sex and hormone biology, discuss what these advances mean for merging the two fields, review the current mouse model literature, raise major unresolved questions, and offer a research framework that incorporates human reproductive aging for future studies aimed at translational discoveries in this important area. Unraveling human relevant pathways in sex and hormone-based biology may ultimately pave the way to novel and urgently needed treatments for AD and other neurodegenerative diseases. PMID:23126652

An experimental and finite element poroelastic creep response analysis of an intervertebral hydrogel disc model in axial compression.

PubMed

Silva, P; Crozier, S; Veidt, M; Pearcy, M J

2005-07-01

A hydrogel intervertebral disc (IVD) model consisting of an inner nucleus core and an outer anulus ring was manufactured from 30 and 35% by weight Poly(vinyl alcohol) hydrogel (PVA-H) concentrations and subjected to axial compression in between saturated porous endplates at 200 N for 11 h, 30 min. Repeat experiments (n=4) on different samples (N=2) show good reproducibility of fluid loss and axial deformation. An axisymmetric nonlinear poroelastic finite element model with variable permeability was developed using commercial finite element software to compare axial deformation and predicted fluid loss with experimental data. The FE predictions indicate differential fluid loss similar to that of biological IVDs, with the nucleus losing more water than the anulus, and there is overall good agreement between experimental and finite element predicted fluid loss. The stress distribution pattern indicates important similarities with the biological IVD that includes stress transference from the nucleus to the anulus upon sustained loading and renders it suitable as a model that can be used in future studies to better understand the role of fluid and stress in biological IVDs.

Clusters of Monoisotopic Elements for Calibration in (TOF) Mass Spectrometry

NASA Astrophysics Data System (ADS)

Kolářová, Lenka; Prokeš, Lubomír; Kučera, Lukáš; Hampl, Aleš; Peňa-Méndez, Eladia; Vaňhara, Petr; Havel, Josef

2017-03-01

Precise calibration in TOF MS requires suitable and reliable standards, which are not always available for high masses. We evaluated inorganic clusters of the monoisotopic elements gold and phosphorus (Au n +/Au n - and P n +/P n -) as an alternative to peptides or proteins for the external and internal calibration of mass spectra in various experimental and instrumental scenarios. Monoisotopic gold or phosphorus clusters can be easily generated in situ from suitable precursors by laser desorption/ionization (LDI) or matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Their use offers numerous advantages, including simplicity of preparation, biological inertness, and exact mass determination even at lower mass resolution. We used citrate-stabilized gold nanoparticles to generate gold calibration clusters, and red phosphorus powder to generate phosphorus clusters. Both elements can be added to samples to perform internal calibration up to mass-to-charge ( m/z) 10-15,000 without significantly interfering with the analyte. We demonstrated the use of the gold and phosphorous clusters in the MS analysis of complex biological samples, including microbial standards and total extracts of mouse embryonic fibroblasts. We believe that clusters of monoisotopic elements could be used as generally applicable calibrants for complex biological samples.

Australian Biology Test Item Bank, Years 11 and 12. Volume II: Year 12.

ERIC Educational Resources Information Center

Brown, David W., Ed.; Sewell, Jeffrey J., Ed.

This document consists of test items which are applicable to biology courses throughout Australia (irrespective of course materials used); assess key concepts within course statement (for both core and optional studies); assess a wide range of cognitive processes; and are relevant to current biological concepts. These items are arranged under…

Context, Cortex, and Dopamine: A Connectionist Approach to Behavior and Biology in Schizophrenia.

ERIC Educational Resources Information Center

Cohen, Jonathan D.; Servan-Schreiber, David

1992-01-01

Using a connectionist framework, it is possible to develop models exploring effects of biologically relevant variables on behavior. The ability of such models to explain schizophrenic behavior in terms of biological disturbances is considered, and computer models are presented that simulate normal and schizophrenic behavior in an attentional task.…

Understanding the side effects of classical biological control

Treesearch

Dean Pearson

2008-01-01

Classical biological control involves the use of imported natural enemies to suppress or control populations of the target pest species below an economically or ecologically relevant threshold. Biological control is a useful tool for mitigating the impacts of exotic invasive plants; however, its application is not without risk (see Carruthers and D’Antonio...

"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…

Australian Biology Test Item Bank, Years 11 and 12. Volume I: Year 11.

ERIC Educational Resources Information Center

Brown, David W., Ed.; Sewell, Jeffrey J., Ed.

This document consists of test items which are applicable to biology courses throughout Australia (irrespective of course materials used); assess key concepts within course statement (for both core and optional studies); assess a wide range of cognitive processes; and are relevant to current biological concepts. These items are arranged under…

Abasy Atlas: a comprehensive inventory of systems, global network properties and systems-level elements across bacteria.

PubMed

Ibarra-Arellano, Miguel A; Campos-González, Adrián I; Treviño-Quintanilla, Luis G; Tauch, Andreas; Freyre-González, Julio A

2016-01-01

The availability of databases electronically encoding curated regulatory networks and of high-throughput technologies and methods to discover regulatory interactions provides an invaluable source of data to understand the principles underpinning the organization and evolution of these networks responsible for cellular regulation. Nevertheless, data on these sources never goes beyond the regulon level despite the fact that regulatory networks are complex hierarchical-modular structures still challenging our understanding. This brings the necessity for an inventory of systems across a large range of organisms, a key step to rendering feasible comparative systems biology approaches. In this work, we take the first step towards a global understanding of the regulatory networks organization by making a cartography of the functional architectures of diverse bacteria. Abasy ( A: cross- BA: cteria SY: stems) Atlas provides a comprehensive inventory of annotated functional systems, global network properties and systems-level elements (global regulators, modular genes shaping functional systems, basal machinery genes and intermodular genes) predicted by the natural decomposition approach for reconstructed and meta-curated regulatory networks across a large range of bacteria, including pathogenically and biotechnologically relevant organisms. The meta-curation of regulatory datasets provides the most complete and reliable set of regulatory interactions currently available, which can even be projected into subsets by considering the force or weight of evidence supporting them or the systems that they belong to. Besides, Abasy Atlas provides data enabling large-scale comparative systems biology studies aimed at understanding the common principles and particular lifestyle adaptions of systems across bacteria. Abasy Atlas contains systems and system-level elements for 50 regulatory networks comprising 78 649 regulatory interactions covering 42 bacteria in nine taxa, containing 3708 regulons and 1776 systems. All this brings together a large corpus of data that will surely inspire studies to generate hypothesis regarding the principles governing the evolution and organization of systems and the functional architectures controlling them.Database URL: http://abasy.ccg.unam.mx. © The Author(s) 2016. Published by Oxford University Press.

Identifying structural variation in haploid microbial genomes from short-read resequencing data using breseq.

PubMed

Barrick, Jeffrey E; Colburn, Geoffrey; Deatherage, Daniel E; Traverse, Charles C; Strand, Matthew D; Borges, Jordan J; Knoester, David B; Reba, Aaron; Meyer, Austin G

2014-11-29

Mutations that alter chromosomal structure play critical roles in evolution and disease, including in the origin of new lifestyles and pathogenic traits in microbes. Large-scale rearrangements in genomes are often mediated by recombination events involving new or existing copies of mobile genetic elements, recently duplicated genes, or other repetitive sequences. Most current software programs for predicting structural variation from short-read DNA resequencing data are intended primarily for use on human genomes. They typically disregard information in reads mapping to repeat sequences, and significant post-processing and manual examination of their output is often required to rule out false-positive predictions and precisely describe mutational events. We have implemented an algorithm for identifying structural variation from DNA resequencing data as part of the breseq computational pipeline for predicting mutations in haploid microbial genomes. Our method evaluates the support for new sequence junctions present in a clonal sample from split-read alignments to a reference genome, including matches to repeat sequences. Then, it uses a statistical model of read coverage evenness to accept or reject these predictions. Finally, breseq combines predictions of new junctions and deleted chromosomal regions to output biologically relevant descriptions of mutations and their effects on genes. We demonstrate the performance of breseq on simulated Escherichia coli genomes with deletions generating unique breakpoint sequences, new insertions of mobile genetic elements, and deletions mediated by mobile elements. Then, we reanalyze data from an E. coli K-12 mutation accumulation evolution experiment in which structural variation was not previously identified. Transposon insertions and large-scale chromosomal changes detected by breseq account for ~25% of spontaneous mutations in this strain. In all cases, we find that breseq is able to reliably predict structural variation with modest read-depth coverage of the reference genome (>40-fold). Using breseq to predict structural variation should be useful for studies of microbial epidemiology, experimental evolution, synthetic biology, and genetics when a reference genome for a closely related strain is available. In these cases, breseq can discover mutations that may be responsible for important or unintended changes in genomes that might otherwise go undetected.

WHO Expert Committee on Biological Standardization.

PubMed

2002-01-01

This report presents the recommendations of a WHO Expert Committee commissioned to coordinate activities leading to the adoption of international recommendations for the production and quality control of vaccines and other biologicals and the establishment of international biological reference materials. The report starts with a discussion of general issues brought to the attention of the Committee and provides information on issues relevant to international guidelines, recommendations and other matters related to the manufacture and quality control of biologicals. This is followed by information on the status and development of reference materials for bovine spongiform encephalopathy, various antigens, blood products, cytokines, growth factors and endocrinological substances. The second part of the report, of particular interest to manufacturers and national control authorities, contains sets of recommendations for the production and control of poliomyelitis vaccine (oral) and poliomyelitis vaccine (inactivated) and guidelines for the production and control of live attenuated Japanese encephalitis vaccine. Also included are lists of recommendations and guidelines for biological substances used in medicine, and other relevant documents.

Light rare earth element depletion during Deepwater Horizon blowout methanotrophy.

PubMed

Shiller, A M; Chan, E W; Joung, D J; Redmond, M C; Kessler, J D

2017-09-04

Rare earth elements have generally not been thought to have a biological role. However, recent work has demonstrated that the light REEs (LREEs: La, Ce, Pr, and Nd) are essential for at least some methanotrophs, being co-factors in the XoxF type of methanol dehydrogenase (MDH). We show here that dissolved LREEs were significantly removed in a submerged plume of methane-rich water during the Deepwater Horizon (DWH) well blowout. Furthermore, incubation experiments conducted with naturally methane-enriched waters from hydrocarbon seeps in the vicinity of the DWH wellhead also showed LREE removal concurrent with methane consumption. Metagenomic sequencing of incubation samples revealed that LREE-containing MDHs were present. Our field and laboratory observations provide further insight into the biochemical pathways of methanotrophy during the DWH blowout. Additionally, our results are the first observations of direct biological alteration of REE distributions in oceanic systems. In view of the ubiquity of LREE-containing MDHs in oceanic systems, our results suggest that biological uptake of LREEs is an overlooked aspect of the oceanic geochemistry of this group of elements previously thought to be biologically inactive and an unresolved factor in the flux of methane, a potent greenhouse gas, from the ocean.

Scanning transmission ion microscopy mass measurements for quantitative trace element analysis within biological samples and validation using atomic force microscopy thickness measurements

NASA Astrophysics Data System (ADS)

Devès, Guillaume; Cohen-Bouhacina, Touria; Ortega, Richard

2004-10-01

We used the nuclear microprobe techniques, micro-PIXE (particle-induced X-ray emission), micro-RBS (Rutherford backscattering spectrometry) and scanning transmission ion microscopy (STIM) in order to perform the characterization of trace element content and spatial distribution within biological samples (dehydrated cultured cells, tissues). The normalization of PIXE results was usually expressed in terms of sample dry mass as determined by micro-RBS recorded simultaneously to micro-PIXE. However, the main limit of RBS mass measurement is the sample mass loss occurring during irradiation and which could be up to 30% of the initial sample mass. We present here a new methodology for PIXE normalization and quantitative analysis of trace element within biological samples based on dry mass measurement performed by mean of STIM. The validation of STIM cell mass measurements was obtained in comparison with AFM sample thickness measurements. Results indicated the reliability of STIM mass measurement performed on biological samples and suggested that STIM should be performed for PIXE normalization. Further information deriving from direct confrontation of AFM and STIM analysis could as well be obtained, like in situ measurements of cell specific gravity within cells compartment (nucleolus and cytoplasm).

The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 2 Core.

PubMed

Hucka, Michael; Bergmann, Frank T; Dräger, Andreas; Hoops, Stefan; Keating, Sarah M; Le Novère, Nicolas; Myers, Chris J; Olivier, Brett G; Sahle, Sven; Schaff, James C; Smith, Lucian P; Waltemath, Dagmar; Wilkinson, Darren J

2018-03-09

Computational models can help researchers to interpret data, understand biological functions, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that different software systems can exchange. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 2 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML, their encoding in XML (the eXtensible Markup Language), validation rules that determine the validity of an SBML document, and examples of models in SBML form. The design of Version 2 differs from Version 1 principally in allowing new MathML constructs, making more child elements optional, and adding identifiers to all SBML elements instead of only selected elements. Other materials and software are available from the SBML project website at http://sbml.org/.

Evaluation of cryoanalysis as a tool for analyzing elemental distribution in "live" tardigrades using micro-PIXE

NASA Astrophysics Data System (ADS)

Nilsson, E. J. C.; Pallon, J.; Przybylowicz, W. J.; Wang, Y. D.; Jönsson, K. I.

2014-08-01

Although heavy on labor and equipment, thus not often applied, cryoanalysis of frozen hydrated biological specimens can provide information that better reflects the living state of the organism, compared with analysis in the freeze-dried state. In this paper we report a study where the cryoanalysis facility with cryosectioning capabilities at Materials Research Department, iThemba LABS, South Africa was employed to evaluate the usefulness of combining three ion beam analytical methods (μPIXE, RBS and STIM) to analyze a biological target where a better elemental compositional description is needed - the tardigrade. Imaging as well as quantification results are of interest. In a previous study, the element composition and redistribution of elements in the desiccated and active states of two tardigrade species was investigated. This study included analysis of both whole and sectioned tardigrades, and the aim was to analyze each specimen twice; first frozen hydrated and later freeze-dried. The combination of the three analytical techniques proved useful: elements from C to Rb in the tardigrades could be determined and certain differences in distribution of elements between the frozen hydrated and the freeze-dried states were observed. RBS on frozen hydrated specimens provided knowledge of matrix elements.

Fluorine--a current literature review. An NRC and ATSDR based review of safety standards for exposure to fluorine and fluorides.

PubMed

Prystupa, Jeff

2011-02-01

A review of the literature of the element fluorine and its bonded-form, fluoride, was undertaken. Generally regarded as safe, an expanding body of literature reveals that fluoride's toxicity has been unappreciated, un-scrutinized, and hidden for over 70 years. The context for the literature search and review was an environmental climate-change study, which demonstrated widespread fluoride contamination by smokestack emissions from coal-fired electricity-generating plants. The objective of this review is to educate and inform regarding the ubiquitous presence and harmful nature of this now ever-present corrosive and reactive toxin. Methods include examination of national health agency reviews, primarily the National Research Council (NRC), Agency for Toxic Substances & Disease Registry (ATSDR), standard medical toxicology references, text books, as well as reports and documents from both private and public research as well as consumer-based NGOs. Study criteria were chosen for relevancy to the subject of the toxicity of fluoride. Fluoride is the extreme electron scavenger, the most corrosive of all elements, as well as the most-reactive. Fluoride appears to attack living tissues, via several mechanisms. Fluoride renders strong evidence that it is a non-biological chemical, demonstrating no observed beneficial function or role in organic chemistry, beyond use as a pesticide or insecticide. Fluorine has a strong role to play in industry, having been utilized extensively in metals, plastics, paints, aluminium, steel, and uranium production. Due to its insatiable appetite for calcium, fluorine and fluorides likely represent a form of chemistry that is incompatible with biological tissues and organ system functions. Based on an analysis of the affects of fluoride demonstrated consistently in the literature, safe levels have not been determined nor standardized. Mounting evidence presents conflicting value to its presence in biological settings and applications. Evidence examined in this review of the literature, and specifically the recent report by the National Research Council (NRC), offer strong support for an immediate reconsideration concerning risk vs benefit. Consensus recommendations from several sources are presented.

Modernize or Mothball; Ship to Shore Watercraft Must be Modernized to Remain Relevant

DTIC Science & Technology

2017-05-12

remain relevant. 5a. CONTRACT NUMBER moderni to remain relevant. 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ...5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT...NUMBER Joint Military Operations Department Naval War College 686 Cushing Road Newport, RI 02841-1207

High Throughput Analyses of Budding Yeast ARSs Reveal New DNA Elements Capable of Conferring Centromere-Independent Plasmid Propagation

PubMed Central

Hoggard, Timothy; Liachko, Ivan; Burt, Cassaundra; Meikle, Troy; Jiang, Katherine; Craciun, Gheorghe; Dunham, Maitreya J.; Fox, Catherine A.

2016-01-01

The ability of plasmids to propagate in Saccharomyces cerevisiae has been instrumental in defining eukaryotic chromosomal control elements. Stable propagation demands both plasmid replication, which requires a chromosomal replication origin (i.e., an ARS), and plasmid distribution to dividing cells, which requires either a chromosomal centromere for segregation or a plasmid-partitioning element. While our knowledge of yeast ARSs and centromeres is relatively advanced, we know less about chromosomal regions that can function as plasmid partitioning elements. The Rap1 protein-binding site (RAP1) present in transcriptional silencers and telomeres of budding yeast is a known plasmid-partitioning element that functions to anchor a plasmid to the inner nuclear membrane (INM), which in turn facilitates plasmid distribution to daughter cells. This Rap1-dependent INM-anchoring also has an important chromosomal role in higher-order chromosomal structures that enhance transcriptional silencing and telomere stability. Thus, plasmid partitioning can reflect fundamental features of chromosome structure and biology, yet a systematic screen for plasmid partitioning elements has not been reported. Here, we couple deep sequencing with competitive growth experiments of a plasmid library containing thousands of short ARS fragments to identify new plasmid partitioning elements. Competitive growth experiments were performed with libraries that differed only in terms of the presence or absence of a centromere. Comparisons of the behavior of ARS fragments in the two experiments allowed us to identify sequences that were likely to drive plasmid partitioning. In addition to the silencer RAP1 site, we identified 74 new putative plasmid-partitioning motifs predicted to act as binding sites for DNA binding proteins enriched for roles in negative regulation of gene expression and G2/M-phase associated biology. These data expand our knowledge of chromosomal elements that may function in plasmid partitioning and suggest underlying biological roles shared by such elements. PMID:26865697

Exploring High School Biology Students' Engagement with More and Less Epistemologically Considerate Texts

ERIC Educational Resources Information Center

Kloser, Matthew

2013-01-01

Texts play an integral role in science research and science classrooms yet biology textbooks have traditionally failed to reflect the epistemic elements of the discipline such as justification of claims and visual representations of empirical data. This study investigates high school biology students' reading experiences when engaging more…

Conceptual Elements: A Detailed Framework to Support and Assess Student Learning of Biology Core Concepts

ERIC Educational Resources Information Center

Cary, Tawnya; Branchaw, Janet

2017-01-01

The "Vision and Change in Undergraduate Biology Education: Call to Action" report has inspired and supported a nationwide movement to restructure undergraduate biology curricula to address overarching disciplinary concepts and competencies. The report outlines the concepts and competencies generally but does not provide a detailed…

32 CFR Appendix A to 32 Cfr Part 65 - Additional Reporting Requirements

Code of Federal Regulations, 2010 CFR

2010-07-01

... Requirements Table 1—Data Elements From DoD Instruction 1336.5 and DoD Instruction 7730.54 Relevant to This Part Field Data element name Description References 947-954 d. Initial Entry Training End Calendar Date... title 10, U.S.C See DoD Instruction 1336.5 for additional data elements. 955-971 Active Duty Loan...

Biological conversion of anglesite (PbSO(4)) and lead waste from spent car batteries to galena (PbS).

PubMed

Weijma, Jan; De Hoop, Klaas; Bosma, Wobby; Dijkman, Henk

2002-01-01

Lead paste, a solid mixture containing PbSO(4), PbO(2), PbO/Pb(OH)(2) precipitate, and elemental Pb, is one of the main waste fractions from spent car batteries. Biological sulfidation represents a new process for recovery of lead from this waste. In this process the lead salts in lead paste are converted to galena (PbS) by sulfate-reducing bacteria. This paper investigates a continuous process for sulfidation of anglesite (PbSO(4)), the main constituent of lead paste, and lead paste, consisting of a laboratory-scale gas-lift bioreactor to which a slurry of anglesite or lead paste was supplied. Sulfate or elemental sulfur was added as an additional sulfur source. Hydrogen gas served as an electron donor for the biological reduction of sulfate and elemental sulfur to sulfide by sulfate- and sulfur-reducing bacteria. Anglesite was almost completely converted to galena at a loading rate of 19 kg of PbSO(4) m(-)(3) day(-)(1), producing a sludge of which the crystalline lead phases consisted of >98% PbS (galena) and 1-2% elemental Pb. With lead paste, stable sulfidation rates of up to 17 kg of lead paste m(-)(3) day(-)(1) were demonstrated, producing a sludge of which the crystalline lead phases consisted of an estimated >96% PbS, 1-2% elemental Pb, and 1-2% PbO(2).

Particulate Trace Element Cycling in a Diatom Bloom at Station ALOHA

NASA Astrophysics Data System (ADS)

Weisend, R.; Morton, P. L.; Landing, W. M.; Fitzsimmons, J. N.; Hayes, C. T.; Boyle, E. A.

2014-12-01

Phytoplankton in oligotrophic marine deserts depend on remote sources to supply trace nutrients. To examine these sources, marine particulate matter samples from the central North Pacific (Station ALOHA) were collected during the July-August 2012 HOE-DYLAN cruises and analyzed for a suite of trace (e.g., Fe, Mn) and major (e.g. Al, P) elements. Daily surface SPM samples were examined for evidence of atmospheric deposition and biological uptake, while five vertical profiles were examined for evidence of surface vertical export and subsurface horizontal transport from nearby sources (e.g., margin sediments, hydrothermal plumes). Maxima in surface particulate P (a biological tracer) corresponded with a diatom bloom, and surprisingly also coincided with maxima in particulate Al (typically a tracer for lithogenic inputs). The surface particulate Al distributions likely result from the adsorption of dissolved Al onto diatom silica frustules, not from atmospheric dust deposition. In addition, a subsurface maximum in particulate Al and P was observed four days later at 75m, possibly resulting from vertical export of the surface diatom bloom. The distributions of other bioactive trace elements (e.g. Cd, Co, Cu) will be presented in the context of the diatom bloom and other biological, chemical and physical features. A second, complementary poster is also being presented which examines the cycling of trace elements in lithogenic particles (Morton et al., "Trace Element Cycling in Lithogenic Particles at Station ALOHA").

Spatial distribution and potential biological risk of some metals in relation to granulometric content in core sediments from Chilika Lake, India.

PubMed

Barik, Saroja K; Muduli, Pradipta R; Mohanty, Bita; Rath, Prasanta; Samanta, Srikanta

2018-01-01

The article presents first systematic report on the concentration of selected major elements [iron (Fe) and manganese (Mn)] and minor elements [zinc (Zn), copper (Cu), chromium (Cr), lead (Pb), nickel (Ni), and cobalt (Co)] from the core sediment of Chilika Lake, India. The analyzed samples revealed higher content of Pb than the background levels in the entire study area. The extent of contamination from minor and major elements is expressed by assessing (i) the metal enrichments in the sediment through the calculations of anthropogenic factor (AF), pollution load index (PLI), Enrichment factor (EF), and geoaccumulation index (Igeo) and (ii) potential biological risks by the use of sediment quality guidelines like effect range median (ERM) and effect range low (ERL) benchmarks. The estimated indices indicated that sediment is enriched with Pb, Ni, Cr, Cu and Co. The enrichment of these elements seems to be due to the fine granulometric characteristics of the sediment with Fe and Mn oxyhydroxides being the main metal carriers and fishing boats using low grade paints, fuel, and fishing technology using lead beads fixed to fishing nets. Trace element input to the Chilika lake needs to be monitored with due emphasis on Cr and Pb contaminations since the ERM and ERL benchmarks indicated potential biological risk with these metals.

Biological monitoring of occupational exposure to inorganic arsenic

PubMed Central

Apostoli, P.; Bartoli, D.; Alessio, L.; Buchet, J. P.

1999-01-01

OBJECTIVES: This study was undertaken to assess reliable biological indicators for monitoring the occupational exposure to inorganic arsenic (iAs), taking into account the possible confounding role of arsenicals present in food and of the element present in drinking water. METHODS: 51 Glass workers exposed to As trioxide were monitored by measuring dust in the breathing zone, with personal air samplers. Urine samples at the end of work shift were analysed for biological monitoring. A control group of 39 subjects not exposed to As, and eight volunteers who drank water containing about 45 micrograms/l iAs for a week were also considered. Plasma mass spectrometry (ICP-MS) was used for the analysis of total As in air and urine samples, whereas the urinary As species (trivalent, As3; pentavalent, As5; monomethyl arsonic acid, MMA; dimethyl arsinic acid, DMA; arsenobetaine, AsB) were measured by liquid chromatography coupled with plasma mass spectrometry (HPLC-MS) RESULTS: Environmental concentrations of As in air varied widely (mean 84 micrograms/m3, SD 61, median 40) and also the sum of urinary iAs MMA and DMA, varied among the groups of exposed subjects (mean 106 micrograms/l, SD 84, median 65). AsB was the most excreted species (34% of total As) followed by DMA (28%), MMA (26%), and As3 + As5 (12%). In the volunteers who drank As in the water the excretion of MMA and DMA increased (from a median of 0.5 to 5 micrograms/day for MMA and from 4 to 13 micrograms/day for DMA). The best correlations between As in air and its urinary species were found for total iAs and As3 + As5. CONCLUSIONS: To avoid the effect of As from sources other than occupation on urinary species of the element, in particular on DMA, it is proposed that urinary As3 + As5 may an indicator for monitoring the exposure to iAs. For concentrations of 10 micrograms/m3 the current environmental limit for iAs, the limit for urinary As3 + As5 was calculated to be around 5 micrograms/l, even if the wide variation of values needs critical evaluation and application of data. The choice of this indicator might be relevant also from a toxicological point of view. Trivalent arsenic is in fact the most active species and its measure in urine could be the best indicator of some critical effects of the element, such as cancer.   PMID:10658539

Biological monitoring of occupational exposure to inorganic arsenic.

PubMed

Apostoli, P; Bartoli, D; Alessio, L; Buchet, J P

1999-12-01

This study was undertaken to assess reliable biological indicators for monitoring the occupational exposure to inorganic arsenic (iAs), taking into account the possible confounding role of arsenicals present in food and of the element present in drinking water. 51 Glass workers exposed to As trioxide were monitored by measuring dust in the breathing zone, with personal air samplers. Urine samples at the end of work shift were analysed for biological monitoring. A control group of 39 subjects not exposed to As, and eight volunteers who drank water containing about 45 micrograms/l iAs for a week were also considered. Plasma mass spectrometry (ICP-MS) was used for the analysis of total As in air and urine samples, whereas the urinary As species (trivalent, As3; pentavalent, As5; monomethyl arsonic acid, MMA; dimethyl arsinic acid, DMA; arsenobetaine, AsB) were measured by liquid chromatography coupled with plasma mass spectrometry (HPLC-MS) RESULTS: Environmental concentrations of As in air varied widely (mean 84 micrograms/m3, SD 61, median 40) and also the sum of urinary iAs MMA and DMA, varied among the groups of exposed subjects (mean 106 micrograms/l, SD 84, median 65). AsB was the most excreted species (34% of total As) followed by DMA (28%), MMA (26%), and As3 + As5 (12%). In the volunteers who drank As in the water the excretion of MMA and DMA increased (from a median of 0.5 to 5 micrograms/day for MMA and from 4 to 13 micrograms/day for DMA). The best correlations between As in air and its urinary species were found for total iAs and As3 + As5. To avoid the effect of As from sources other than occupation on urinary species of the element, in particular on DMA, it is proposed that urinary As3 + As5 may an indicator for monitoring the exposure to iAs. For concentrations of 10 micrograms/m3 the current environmental limit for iAs, the limit for urinary As3 + As5 was calculated to be around 5 micrograms/l, even if the wide variation of values needs critical evaluation and application of data. The choice of this indicator might be relevant also from a toxicological point of view. Trivalent arsenic is in fact the most active species and its measure in urine could be the best indicator of some critical effects of the element, such as cancer.

ICE Afe 1, an actively excising genetic element from the biomining bacterium Acidithiobacillus ferrooxidans.

PubMed

Bustamante, Paula; Covarrubias, Paulo C; Levicán, Gloria; Katz, Assaf; Tapia, Pablo; Holmes, David; Quatrini, Raquel; Orellana, Omar

2012-01-01

Integrative conjugative elements (ICEs) are self-transferred mobile genetic elements that contribute to horizontal gene transfer. An ICE (ICEAfe1) was identified in the genome of Acidithiobacillus ferrooxidans ATCC 23270. Excision of the element and expression of relevant genes under normal and DNA-damaging growth conditions was analyzed. Bioinformatic tools and DNA amplification methods were used to identify and to assess the excision and expression of genes related to the mobility of the element. Both basal and mitomycin C-inducible excision as well as expression and induction of the genes for integration/excision are demonstrated, suggesting that ICEAfe1 is an actively excising SOS-regulated mobile genetic element. The presence of a complete set of genes encoding self-transfer functions that are induced in response to DNA damage caused by mitomycin C additionally suggests that this element is capable of conjugative transfer to suitable recipient strains. Transfer of ICEAfe1 may provide selective advantages to other acidophiles in this ecological niche through dissemination of gene clusters expressing transfer RNAs, CRISPRs, and exopolysaccharide biosynthesis enzymes, probably by modification of translation efficiency, resistance to bacteriophage infection and biofilm formation, respectively. These data open novel avenues of research on conjugative transformation of biotechnologically relevant microorganisms recalcitrant to genetic manipulation. Copyright © 2013 S. Karger AG, Basel.

Students' Personal Connection with Science: Investigating the Multidimensional Phenomenological Structure of Self-Relevance

ERIC Educational Resources Information Center

Hartwell, Matthew; Kaplan, Avi

2018-01-01

This paper presents findings from a two-phase mixed methods study investigating the phenomenological structure of self-relevance among ninth-grade junior high school biology students (Phase 1: N = 118; Phase 2: N = 139). We begin with a phenomenological multidimensional definition of self-relevance as comprising three dimensions: the academic…

Novel green tissue-specific synthetic promoters and cis-regulatory elements in rice.

PubMed

Wang, Rui; Zhu, Menglin; Ye, Rongjian; Liu, Zuoxiong; Zhou, Fei; Chen, Hao; Lin, Yongjun

2015-12-11

As an important part of synthetic biology, synthetic promoter has gradually become a hotspot in current biology. The purposes of the present study were to synthesize green tissue-specific promoters and to discover green tissue-specific cis-elements. We first assembled several regulatory sequences related to tissue-specific expression in different combinations, aiming to obtain novel green tissue-specific synthetic promoters. GUS assays of the transgenic plants indicated 5 synthetic promoters showed green tissue-specific expression patterns and different expression efficiencies in various tissues. Subsequently, we scanned and counted the cis-elements in different tissue-specific promoters based on the plant cis-elements database PLACE and the rice cDNA microarray database CREP for green tissue-specific cis-element discovery, resulting in 10 potential cis-elements. The flanking sequence of one potential core element (GEAT) was predicted by bioinformatics. Then, the combination of GEAT and its flanking sequence was functionally identified with synthetic promoter. GUS assays of the transgenic plants proved its green tissue-specificity. Furthermore, the function of GEAT flanking sequence was analyzed in detail with site-directed mutagenesis. Our study provides an example for the synthesis of rice tissue-specific promoters and develops a feasible method for screening and functional identification of tissue-specific cis-elements with their flanking sequences at the genome-wide level in rice.

Bioforensics: Characterization of biological weapons agents by NanoSIMS

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

Weber, P K; Ghosal, S; Leighton, T J

2007-02-26

The anthrax attacks of Fall 2001 highlight the need to develop forensic methods based on multiple identifiers to determine the origin of biological weapons agents. Genetic typing methods (i.e., DNA and RNA-based) provide one attribution technology, but genetic information alone is not usually sufficient to determine the provenance of the material. Non-genetic identifiers, including elemental and isotopic signatures, provide complementary information that can be used to identify the means, geographic location and date of production. Under LDRD funding, we have successfully developed the techniques necessary to perform bioforensic characterization with the NanoSIMS at the individual spore level. We have developedmore » methods for elemental and isotopic characterization at the single spore scale. We have developed methods for analyzing spore sections to map elemental abundance within spores. We have developed rapid focused ion beam (FIB) sectioning techniques for spores to preserve elemental and structural integrity. And we have developed a high-resolution depth profiling method to characterize the elemental distribution in individual spores without sectioning. We used these newly developed methods to study the controls on elemental abundances in spores, characterize the elemental distribution of in spores, and to study elemental uptake by spores. Our work under this LDRD project attracted FBI and DHS funding for applied purposes.« less

Invited review article: Advanced light microscopy for biological space research.

PubMed

De Vos, Winnok H; Beghuin, Didier; Schwarz, Christian J; Jones, David B; van Loon, Jack J W A; Bereiter-Hahn, Juergen; Stelzer, Ernst H K

2014-10-01

As commercial space flights have become feasible and long-term extraterrestrial missions are planned, it is imperative that the impact of space travel and the space environment on human physiology be thoroughly characterized. Scrutinizing the effects of potentially detrimental factors such as ionizing radiation and microgravity at the cellular and tissue level demands adequate visualization technology. Advanced light microscopy (ALM) is the leading tool for non-destructive structural and functional investigation of static as well as dynamic biological systems. In recent years, technological developments and advances in photochemistry and genetic engineering have boosted all aspects of resolution, readout and throughput, rendering ALM ideally suited for biological space research. While various microscopy-based studies have addressed cellular response to space-related environmental stressors, biological endpoints have typically been determined only after the mission, leaving an experimental gap that is prone to bias results. An on-board, real-time microscopical monitoring device can bridge this gap. Breadboards and even fully operational microscope setups have been conceived, but they need to be rendered more compact and versatile. Most importantly, they must allow addressing the impact of gravity, or the lack thereof, on physiologically relevant biological systems in space and in ground-based simulations. In order to delineate the essential functionalities for such a system, we have reviewed the pending questions in space science, the relevant biological model systems, and the state-of-the art in ALM. Based on a rigorous trade-off, in which we recognize the relevance of multi-cellular systems and the cellular microenvironment, we propose a compact, but flexible concept for space-related cell biological research that is based on light sheet microscopy.

Invited Review Article: Advanced light microscopy for biological space research

NASA Astrophysics Data System (ADS)

De Vos, Winnok H.; Beghuin, Didier; Schwarz, Christian J.; Jones, David B.; van Loon, Jack J. W. A.; Bereiter-Hahn, Juergen; Stelzer, Ernst H. K.

2014-10-01

As commercial space flights have become feasible and long-term extraterrestrial missions are planned, it is imperative that the impact of space travel and the space environment on human physiology be thoroughly characterized. Scrutinizing the effects of potentially detrimental factors such as ionizing radiation and microgravity at the cellular and tissue level demands adequate visualization technology. Advanced light microscopy (ALM) is the leading tool for non-destructive structural and functional investigation of static as well as dynamic biological systems. In recent years, technological developments and advances in photochemistry and genetic engineering have boosted all aspects of resolution, readout and throughput, rendering ALM ideally suited for biological space research. While various microscopy-based studies have addressed cellular response to space-related environmental stressors, biological endpoints have typically been determined only after the mission, leaving an experimental gap that is prone to bias results. An on-board, real-time microscopical monitoring device can bridge this gap. Breadboards and even fully operational microscope setups have been conceived, but they need to be rendered more compact and versatile. Most importantly, they must allow addressing the impact of gravity, or the lack thereof, on physiologically relevant biological systems in space and in ground-based simulations. In order to delineate the essential functionalities for such a system, we have reviewed the pending questions in space science, the relevant biological model systems, and the state-of-the art in ALM. Based on a rigorous trade-off, in which we recognize the relevance of multi-cellular systems and the cellular microenvironment, we propose a compact, but flexible concept for space-related cell biological research that is based on light sheet microscopy.

ISOL@: an Italian SOLAnaceae genomics resource.

PubMed

Chiusano, Maria Luisa; D'Agostino, Nunzio; Traini, Alessandra; Licciardello, Concetta; Raimondo, Enrico; Aversano, Mario; Frusciante, Luigi; Monti, Luigi

2008-03-26

Present-day '-omics' technologies produce overwhelming amounts of data which include genome sequences, information on gene expression (transcripts and proteins) and on cell metabolic status. These data represent multiple aspects of a biological system and need to be investigated as a whole to shed light on the mechanisms which underpin the system functionality. The gathering and convergence of data generated by high-throughput technologies, the effective integration of different data-sources and the analysis of the information content based on comparative approaches are key methods for meaningful biological interpretations. In the frame of the International Solanaceae Genome Project, we propose here ISOLA, an Italian SOLAnaceae genomics resource. ISOLA (available at http://biosrv.cab.unina.it/isola) represents a trial platform and it is conceived as a multi-level computational environment.ISOLA currently consists of two main levels: the genome and the expression level. The cornerstone of the genome level is represented by the Solanum lycopersicum genome draft sequences generated by the International Tomato Genome Sequencing Consortium. Instead, the basic element of the expression level is the transcriptome information from different Solanaceae species, mainly in the form of species-specific comprehensive collections of Expressed Sequence Tags (ESTs). The cross-talk between the genome and the expression levels is based on data source sharing and on tools that enhance data quality, that extract information content from the levels' under parts and produce value-added biological knowledge. ISOLA is the result of a bioinformatics effort that addresses the challenges of the post-genomics era. It is designed to exploit '-omics' data based on effective integration to acquire biological knowledge and to approach a systems biology view. Beyond providing experimental biologists with a preliminary annotation of the tomato genome, this effort aims to produce a trial computational environment where different aspects and details are maintained as they are relevant for the analysis of the organization, the functionality and the evolution of the Solanaceae family.

Conceptual Elements: A Detailed Framework to Support and Assess Student Learning of Biology Core Concepts

PubMed Central

Cary, Tawnya; Branchaw, Janet

2017-01-01

The Vision and Change in Undergraduate Biology Education: Call to Action report has inspired and supported a nationwide movement to restructure undergraduate biology curricula to address overarching disciplinary concepts and competencies. The report outlines the concepts and competencies generally but does not provide a detailed framework to guide the development of the learning outcomes, instructional materials, and assessment instruments needed to create a reformed biology curriculum. In this essay, we present a detailed Vision and Change core concept framework that articulates key components that transcend subdisciplines and scales for each overarching biological concept, the Conceptual Elements (CE) Framework. The CE Framework was developed using a grassroots approach of iterative revision and incorporates feedback from more than 60 biologists and undergraduate biology educators from across the United States. The final validation step resulted in strong national consensus, with greater than 92% of responders agreeing that each core concept list was ready for use by the biological sciences community, as determined by scientific accuracy and completeness. In addition, we describe in detail how educators and departments can use the CE Framework to guide and document reformation of individual courses as well as entire curricula. PMID:28450444

Biological role of bacterial inclusion bodies: a model for amyloid aggregation.

PubMed

García-Fruitós, Elena; Sabate, Raimon; de Groot, Natalia S; Villaverde, Antonio; Ventura, Salvador

2011-07-01

Inclusion bodies are insoluble protein aggregates usually found in recombinant bacteria when they are forced to produce heterologous protein species. These particles are formed by polypeptides that cross-interact through sterospecific contacts and that are steadily deposited in either the cell's cytoplasm or the periplasm. An important fraction of eukaryotic proteins form inclusion bodies in bacteria, which has posed major problems in the development of the biotechnology industry. Over the last decade, the fine dissection of the quality control system in bacteria and the recognition of the amyloid-like architecture of inclusion bodies have provided dramatic insights on the dynamic biology of these aggregates. We discuss here the relevant aspects, in the interface between cell physiology and structural biology, which make inclusion bodies unique models for the study of protein aggregation, amyloid formation and prion biology in a physiologically relevant background. © 2011 The Authors Journal compilation © 2011 FEBS.

Clinico-pathological and biological prognostic variables in squamous cell carcinoma of the vulva.

PubMed

Gadducci, Angiolo; Tana, Roberta; Barsotti, Cecilia; Guerrieri, Maria Elena; Genazzani, Andrea Riccardo

2012-07-01

Several clinical-pathological parameters have been related to survival of patients with invasive squamous cell carcinoma of the vulva, whereas few studies have investigated the ability of biological variables to predict the clinical outcome of these patients. The present paper reviews the literature data on the prognostic relevance of lymph node-related parameters, primary tumor-related parameters, FIGO stage, blood variables, and tissue biological variables. Regarding these latter, the paper takes into account the analysis of DNA content, cell cycle-regulatory proteins, apoptosis-related proteins, epidermal growth factor receptor [EGFR], and proteins that are involved in tumor invasiveness, metastasis and angiogenesis. At present, the lymph node status and FIGO stage according to the new 2009 classification system are the main predictors for vulvar squamous cell carcinoma, whereas biological variables do not have yet a clinical relevance and their role is still investigational. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Solving the forward problem of magnetoacoustic tomography with magnetic induction by means of the finite element method

NASA Astrophysics Data System (ADS)

Li, Xun; Li, Xu; Zhu, Shanan; He, Bin

2009-05-01

Magnetoacoustic tomography with magnetic induction (MAT-MI) is a recently proposed imaging modality to image the electrical impedance of biological tissue. It combines the good contrast of electrical impedance tomography with the high spatial resolution of sonography. In this paper, a three-dimensional MAT-MI forward problem was investigated using the finite element method (FEM). The corresponding FEM formulae describing the forward problem are introduced. In the finite element analysis, magnetic induction in an object with conductivity values close to biological tissues was first carried out. The stimulating magnetic field was simulated as that generated from a three-dimensional coil. The corresponding acoustic source and field were then simulated. Computer simulation studies were conducted using both concentric and eccentric spherical conductivity models with different geometric specifications. In addition, the grid size for finite element analysis was evaluated for the model calibration and evaluation of the corresponding acoustic field.

The CGTCA sequence motif is essential for biological activity of the vasoactive intestinal peptide gene cAMP-regulated enhancer.

PubMed Central

Fink, J S; Verhave, M; Kasper, S; Tsukada, T; Mandel, G; Goodman, R H

1988-01-01

cAMP-regulated transcription of the human vasoactive intestinal peptide gene is dependent upon a 17-base-pair DNA element located 70 base pairs upstream from the transcriptional initiation site. This element is similar to sequences in other genes known to be regulated by cAMP and to sequences in several viral enhancers. We have demonstrated that the vasoactive intestinal peptide regulatory element is an enhancer that depends upon the integrity of two CGTCA sequence motifs for biological activity. Mutations in either of the CGTCA motifs diminish the ability of the element to respond to cAMP. Enhancers containing the CGTCA motif from the somatostatin and adenovirus genes compete for binding of nuclear proteins from C6 glioma and PC12 cells to the vasoactive intestinal peptide enhancer, suggesting that CGTCA-containing enhancers interact with similar transacting factors. Images PMID:2842787

Solving the Forward Problem of Magnetoacoustic Tomography with Magnetic Induction by Means of the Finite Element Method

PubMed Central

Li, Xun; Li, Xu; Zhu, Shanan; He, Bin

2010-01-01

Magnetoacoustic Tomography with Magnetic Induction (MAT-MI) is a recently proposed imaging modality to image the electrical impedance of biological tissue. It combines the good contrast of electrical impedance tomography with the high spatial resolution of sonography. In this paper, three-dimensional MAT-MI forward problem was investigated using the finite element method (FEM). The corresponding FEM formulas describing the forward problem are introduced. In the finite element analysis, magnetic induction in an object with conductivity values close to biological tissues was first carried out. The stimulating magnetic field was simulated as that generated from a three-dimensional coil. The corresponding acoustic source and field were then simulated. Computer simulation studies were conducted using both concentric and eccentric spherical conductivity models with different geometric specifications. In addition, the grid size for finite element analysis was evaluated for model calibration and evaluation of the corresponding acoustic field. PMID:19351978

Is Education Ready for Depreciation Accounting?

ERIC Educational Resources Information Center

Roberts, Charles T.

1977-01-01

Whenever it is relevant to measure and report the cost of rendering services on a current basis, the use cost or the depreciation allowance of fixed assets used in providing such services is relevant as an element of the measurement and reporting process. (Author)

Status of MAPA (Modular Accelerator Physics Analysis) and the Tech-X Object-Oriented Accelerator Library

NASA Astrophysics Data System (ADS)

Cary, J. R.; Shasharina, S.; Bruhwiler, D. L.

1998-04-01

The MAPA code is a fully interactive accelerator modeling and design tool consisting of a GUI and two object-oriented C++ libraries: a general library suitable for treatment of any dynamical system, and an accelerator library including many element types plus an accelerator class. The accelerator library inherits directly from the system library, which uses hash tables to store any relevant parameters or strings. The GUI can access these hash tables in a general way, allowing the user to invoke a window displaying all relevant parameters for a particular element type or for the accelerator class, with the option to change those parameters. The system library can advance an arbitrary number of dynamical variables through an arbitrary mapping. The accelerator class inherits this capability and overloads the relevant functions to advance the phase space variables of a charged particle through a string of elements. Among other things, the GUI makes phase space plots and finds fixed points of the map. We discuss the object hierarchy of the two libraries and use of the code.

miRNA profiling in gastrointestinal stromal tumors: implication as diagnostic and prognostic markers.

PubMed

Nannini, Margherita; Ravegnini, Gloria; Angelini, Sabrina; Astolfi, Annalisa; Biasco, Guido; Pantaleo, Maria A

2015-01-01

MicroRNAs are a class of short noncoding RNAs, that play a relevant role in multiple biological processes, such as differentiation, proliferation and apoptosis. Gastrointestinal stromal tumors (GIST) are considered as a paradigm of molecular biology in solid tumors worldwide, and after the discovery of specific alterations in the KIT and PDGFRA genes, they have emerged from anonymity to become a model for targeted therapy. Epigenetics have an emerging and relevant role in different steps of GIST biology such as tumorigenesis, disease progression, prognosis and drug resistance. The aim of the present review was to summarize the current evidence about the role of microRNAs in GIST, including their potential application as well as their limits.

Origin of the spike-timing-dependent plasticity rule

NASA Astrophysics Data System (ADS)

Cho, Myoung Won; Choi, M. Y.

2016-08-01

A biological synapse changes its efficacy depending on the difference between pre- and post-synaptic spike timings. Formulating spike-timing-dependent interactions in terms of the path integral, we establish a neural-network model, which makes it possible to predict relevant quantities rigorously by means of standard methods in statistical mechanics and field theory. In particular, the biological synaptic plasticity rule is shown to emerge as the optimal form for minimizing the free energy. It is further revealed that maximization of the entropy of neural activities gives rise to the competitive behavior of biological learning. This demonstrates that statistical mechanics helps to understand rigorously key characteristic behaviors of a neural network, thus providing the possibility of physics serving as a useful and relevant framework for probing life.

Mosaic, self-similarity logic, and biological attraction principles: three explanatory instruments in biology.

PubMed

Agnati, Luigi F; Baluska, Frantisek; Barlow, Peter W; Guidolin, Diego

2009-11-01

From a structural standpoint, living organisms are organized like a nest of Russian matryoshka dolls, in which structures are buried within one another. From a temporal point of view, this type of organization is the result of a history comprised of a set of time backcloths which have accompanied the passage of living matter from its origins up to the present day. The aim of the present paper is to indicate a possible course of this 'passage through time, and suggest how today's complexity has been reached by living organisms. This investigation will employ three conceptual tools, namely the Mosaic, Self-Similarity Logic, and the Biological Attraction principles. Self-Similarity Logic indicates the self-consistency by which elements of a living system interact, irrespective of the spatiotemporal level under consideration. The term Mosaic indicates how, from the same set of elements assembled according to different patterns, it is possible to arrive at completely different constructions: hence, each system becomes endowed with different emergent properties. The Biological Attraction principle states that there is an inherent drive for association and merging of compatible elements at all levels of biological complexity. By analogy with the gravitation law in physics, biological attraction is based on the evidence that each living organism creates an attractive field around itself. This field acts as a sphere of influence that actively attracts similar fields of other biological systems, thereby modifying salient features of the interacting organisms. Three specific organizational levels of living matter, namely the molecular, cellular, and supracellular levels, have been considered in order to analyse and illustrate the interpretative as well as the predictive roles of each of these three explanatory principles.

Separating the wheat from the chaff: systematic identification of functionally relevant noncoding variants in ADHD.

PubMed

Tong, J H S; Hawi, Z; Dark, C; Cummins, T D R; Johnson, B P; Newman, D P; Lau, R; Vance, A; Heussler, H S; Matthews, N; Bellgrove, M A; Pang, K C

2016-11-01

Attention deficit hyperactivity disorder (ADHD) is a highly heritable psychiatric condition with negative lifetime outcomes. Uncovering its genetic architecture should yield important insights into the neurobiology of ADHD and assist development of novel treatment strategies. Twenty years of candidate gene investigations and more recently genome-wide association studies have identified an array of potential association signals. In this context, separating the likely true from false associations ('the wheat' from 'the chaff') will be crucial for uncovering the functional biology of ADHD. Here, we defined a set of 2070 DNA variants that showed evidence of association with ADHD (or were in linkage disequilibrium). More than 97% of these variants were noncoding, and were prioritised for further exploration using two tools-genome-wide annotation of variants (GWAVA) and Combined Annotation-Dependent Depletion (CADD)-that were recently developed to rank variants based upon their likely pathogenicity. Capitalising on recent efforts such as the Encyclopaedia of DNA Elements and US National Institutes of Health Roadmap Epigenomics Projects to improve understanding of the noncoding genome, we subsequently identified 65 variants to which we assigned functional annotations, based upon their likely impact on alternative splicing, transcription factor binding and translational regulation. We propose that these 65 variants, which possess not only a high likelihood of pathogenicity but also readily testable functional hypotheses, represent a tractable shortlist for future experimental validation in ADHD. Taken together, this study brings into sharp focus the likely relevance of noncoding variants for the genetic risk associated with ADHD, and more broadly suggests a bioinformatics approach that should be relevant to other psychiatric disorders.

Carbon nanotubes allow capture of krypton, barium and lead for multichannel biological X-ray fluorescence imaging

NASA Astrophysics Data System (ADS)

Serpell, Christopher J.; Rutte, Reida N.; Geraki, Kalotina; Pach, Elzbieta; Martincic, Markus; Kierkowicz, Magdalena; de Munari, Sonia; Wals, Kim; Raj, Ritu; Ballesteros, Belén; Tobias, Gerard; Anthony, Daniel C.; Davis, Benjamin G.

2016-10-01

The desire to study biology in situ has been aided by many imaging techniques. Among these, X-ray fluorescence (XRF) mapping permits observation of elemental distributions in a multichannel manner. However, XRF imaging is underused, in part, because of the difficulty in interpreting maps without an underlying cellular `blueprint' this could be supplied using contrast agents. Carbon nanotubes (CNTs) can be filled with a wide range of inorganic materials, and thus can be used as `contrast agents' if biologically absent elements are encapsulated. Here we show that sealed single-walled CNTs filled with lead, barium and even krypton can be produced, and externally decorated with peptides to provide affinity for sub-cellular targets. The agents are able to highlight specific organelles in multiplexed XRF mapping, and are, in principle, a general and versatile tool for this, and other modes of biological imaging.

Does Guiding Toward Task-Relevant Information Help Improve Graph Processing and Graph Comprehension of Individuals with Low or High Numeracy? An Eye-Tracker Experiment.

PubMed

Keller, Carmen; Junghans, Alex

2017-11-01

Individuals with low numeracy have difficulties with understanding complex graphs. Combining the information-processing approach to numeracy with graph comprehension and information-reduction theories, we examined whether high numerates' better comprehension might be explained by their closer attention to task-relevant graphical elements, from which they would expect numerical information to understand the graph. Furthermore, we investigated whether participants could be trained in improving their attention to task-relevant information and graph comprehension. In an eye-tracker experiment ( N = 110) involving a sample from the general population, we presented participants with 2 hypothetical scenarios (stomach cancer, leukemia) showing survival curves for 2 treatments. In the training condition, participants received written instructions on how to read the graph. In the control condition, participants received another text. We tracked participants' eye movements while they answered 9 knowledge questions. The sum constituted graph comprehension. We analyzed visual attention to task-relevant graphical elements by using relative fixation durations and relative fixation counts. The mediation analysis revealed a significant ( P < 0.05) indirect effect of numeracy on graph comprehension through visual attention to task-relevant information, which did not differ between the 2 conditions. Training had a significant main effect on visual attention ( P < 0.05) but not on graph comprehension ( P < 0.07). Individuals with high numeracy have better graph comprehension due to their greater attention to task-relevant graphical elements than individuals with low numeracy. With appropriate instructions, both groups can be trained to improve their graph-processing efficiency. Future research should examine (e.g., motivational) mediators between visual attention and graph comprehension to develop appropriate instructions that also result in higher graph comprehension.

Analytical assessment about the simultaneous quantification of releasable pharmaceutical relevant inorganic nanoparticles in tap water and domestic waste water.

PubMed

Krystek, Petra; Bäuerlein, Patrick S; Kooij, Pascal J F

2015-03-15

For pharmaceutical applications, the use of inorganic engineered nanoparticles is of growing interest while silver (Ag) and gold (Au) are the most relevant elements. A few methods were developed recently but the validation and the application testing were quite limited. Therefore, a routinely suitable multi element method for the identification of nanoparticles of different sizes below 100 nm and elemental composition by applying asymmetric flow field flow fraction (AF4) - inductively coupled plasma mass spectrometry (ICPMS) is developed. A complete validation model of the quantification of releasable pharmaceutical relevant inorganic nanoparticles based on Ag and Au is presented for the most relevant aqueous matrices of tap water and domestic waste water. The samples are originated from locations in the Netherlands and it is of great interest to study the unwanted presence of Ag and Au as nanoparticle residues due to possible health and environmental risks. During method development, instability effects are observed for 60 nm and 70 nm Ag ENPs with different capping agents. These effects are studied more closely in relation to matrix effects. Besides the methodological aspects, the obtained analytical results and relevant performance characteristics (e.g. measuring range, limit of detection, repeatability, reproducibility, trueness, and expanded uncertainty of measurement) are determined and discussed. For the chosen aqueous matrices, the results of the performance characteristics are significantly better for Au ENPs in comparison to Ag ENPs; e.g. repeatability and reproducibility are below 10% for all Au ENPs respectively maximal 27% repeatability for larger Ag ENPs. The method is a promising tool for the simultaneous determination of releasable pharmaceutical relevant inorganic nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.

Public Understanding of Plant Biology: Voices from the Bottom of the Garden

ERIC Educational Resources Information Center

Watts, Mike

2015-01-01

Many household gardeners accumulate considerable knowledge of plant biology through a range of informal learning sources. This knowledge seldom relates to school biology and is driven by interest, keen motivation and what is termed here "vital relevance." A small opportunity sample of 12 gardeners (6 M, 6 F) is interviewed in terms of…

Piquing Student Interest with Pharmacology: An Interdisciplinary Program Helps High School Students Learn Biology and Chemistry Principles

ERIC Educational Resources Information Center

Halpin, Myra J.; Hoeffler, Leanne; Schwartz-Bloom, Rochelle D.

2005-01-01

To help students learn science concepts, Pharmacology Education Partnership (PEP)--a science education program that incorporates relevant topics related to drugs and drug abuse into standard biology and chemistry curricula was developed. The interdisciplinary PEP curriculum provides six modules to teach biology and chemistry principles within the…

Regulating Cancer Associated Fibroblast Biology in Prostate Cancer

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0512 TITLE: Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer PRINCIPAL INVESTIGATOR: Andrew...CONTRACT NUMBER Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0512 5c. PROGRAM ELEMENT NUMBER 6... biology to modulate epithelial growth and that inhibitors of this protein kinase have the potential to block this process and thus inhibit tumor growth

Construction of 2,4,6-Trinitrotoluene Biosensors with Novel Sensing Elements from Escherichia coli K-12 MG1655.

PubMed

Tan, Junjie; Kan, Naipeng; Wang, Wei; Ling, Jingyi; Qu, Guolong; Jin, Jing; Shao, Yu; Liu, Gang; Chen, Huipeng

2015-06-01

Detection of 2,4,6-trinitrotoluene (TNT) has been extensively studied since it is a common explosive filling for landmines, posing significant threats to the environment and human safety. The rapid advances in synthetic biology give new hope to detect such toxic and hazardous compounds in a more sensitive and safe way. Biosensor construction anticipates finding sensing elements able to detect TNT. As TNT can induce some physiological responses in E. coli, it may be useful to define the sensing elements from E. coli to detect TNT. An E. coli MG1655 genomic promoter library containing nearly 5,400 elements was constructed. Five elements, yadG, yqgC, aspC, recE, and topA, displayed high sensing specificity to TNT and its indicator compounds 1,3-DNB and 2,4-DNT. Based on this, a whole cell biosensor was constructed using E. coli, in which green fluorescent protein was positioned downstream of the five sensing elements via genetic fusion. The threshold value, detection time, EC200 value, and other aspects of five sensing elements were determined and the minimum responding concentration to TNT was 4.75 mg/L. According to the synthetic biology, the five sensing elements enriched the reservoir of TNT-sensing elements, and provided a more applicable toolkit to be applied in genetic routes and live systems of biosensors in future.

Quantum biology at the cellular level--elements of the research program.

PubMed

Bordonaro, Michael; Ogryzko, Vasily

2013-04-01

Quantum biology is emerging as a new field at the intersection between fundamental physics and biology, promising novel insights into the nature and origin of biological order. We discuss several elements of QBCL (quantum biology at cellular level) - a research program designed to extend the reach of quantum concepts to higher than molecular levels of biological organization. We propose a new general way to address the issue of environmentally induced decoherence and macroscopic superpositions in biological systems, emphasizing the 'basis-dependent' nature of these concepts. We introduce the notion of 'formal superposition' and distinguish it from that of Schroedinger's cat (i.e., a superposition of macroscopically distinct states). Whereas the latter notion presents a genuine foundational problem, the former one contradicts neither common sense nor observation, and may be used to describe cellular 'decision-making' and adaptation. We stress that the interpretation of the notion of 'formal superposition' should involve non-classical correlations between molecular events in a cell. Further, we describe how better understanding of the physics of Life can shed new light on the mechanism driving evolutionary adaptation (viz., 'Basis-Dependent Selection', BDS). Experimental tests of BDS and the potential role of synthetic biology in closing the 'evolvability mechanism' loophole are also discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

De Vos, Winnok H., E-mail: winnok.devos@uantwerpen.be; Cell Systems and Imaging Research Group, Department of Molecular Biotechnology, Ghent University, Ghent; Beghuin, Didier

As commercial space flights have become feasible and long-term extraterrestrial missions are planned, it is imperative that the impact of space travel and the space environment on human physiology be thoroughly characterized. Scrutinizing the effects of potentially detrimental factors such as ionizing radiation and microgravity at the cellular and tissue level demands adequate visualization technology. Advanced light microscopy (ALM) is the leading tool for non-destructive structural and functional investigation of static as well as dynamic biological systems. In recent years, technological developments and advances in photochemistry and genetic engineering have boosted all aspects of resolution, readout and throughput, rendering ALMmore » ideally suited for biological space research. While various microscopy-based studies have addressed cellular response to space-related environmental stressors, biological endpoints have typically been determined only after the mission, leaving an experimental gap that is prone to bias results. An on-board, real-time microscopical monitoring device can bridge this gap. Breadboards and even fully operational microscope setups have been conceived, but they need to be rendered more compact and versatile. Most importantly, they must allow addressing the impact of gravity, or the lack thereof, on physiologically relevant biological systems in space and in ground-based simulations. In order to delineate the essential functionalities for such a system, we have reviewed the pending questions in space science, the relevant biological model systems, and the state-of-the art in ALM. Based on a rigorous trade-off, in which we recognize the relevance of multi-cellular systems and the cellular microenvironment, we propose a compact, but flexible concept for space-related cell biological research that is based on light sheet microscopy.« less

Biological Relevance of Free Radicals and Nitroxides.

PubMed

Prescott, Christopher; Bottle, Steven E

2017-06-01

Nitroxides are stable, kinetically-persistent free radicals which have been successfully used in the study and intervention of oxidative stress, a critical issue pertaining to cellular health which results from an imbalance in the levels of damaging free radicals and redox-active species in the cellular environment. This review gives an overview of some of the biological processes that produce radicals and other reactive oxygen species with relevance to oxidative stress, and then discusses interactions of nitroxides with these species in terms of the use of nitroxides as redox-sensitive probes and redox-active therapeutic agents.

The adequacy of informed consent forms in genetic research in Oman: a pilot study.

PubMed

Al-Riyami, Asya; Jaju, Deepali; Jaju, Sanjay; Silverman, Henry J

2011-08-01

Genetic research presents ethical challenges to the achievement of valid informed consent, especially in developing countries with areas of low literacy. During the last several years, a number of genetic research proposals involving Omani nationals were submitted to the Department of Research and Studies, Ministry of Health, Oman. The objective of this paper is to report on the results of an internal quality assurance initiative to determine the extent of the information being provided in genetic research informed consent forms. In order to achieve this, we developed checklists to assess the inclusion of basic elements of informed consent as well as elements related to the collection and future storage of biological samples. Three of the authors independently evaluated and reached consensus on seven informed consent forms that were available for review. Of the seven consent forms, four had less than half of the basic elements of informed consent. None contained any information regarding whether genetic information relevant to health would be disclosed, whether participants may share in commercial products, the extent of confidentiality protections, and the inclusion of additional consent forms for future storage and use of tissue samples. Information regarding genetic risks and withdrawal of samples were rarely mentioned (1/7), whereas limits on future use of samples were mentioned in 3 of 7 consent forms. Ultimately, consent forms are not likely to address key issues regarding genetic research that have been recommended by research ethics guidelines. We recommend enhanced educational efforts to increase awareness, on the part of researchers, of information that should be included in consent forms. © 2011 Blackwell Publishing Ltd.

Reprogramming somatic cells into iPS cells activates LINE-1 retroelement mobility

PubMed Central

Wissing, Silke; Muñoz-Lopez, Martin; Macia, Angela; Yang, Zhiyuan; Montano, Mauricio; Collins, William; Garcia-Perez, Jose Luis; Moran, John V.; Greene, Warner C.

2012-01-01

Long interspersed element-1 (LINE-1 or L1) retrotransposons account for nearly 17% of human genomic DNA and represent a major evolutionary force that has reshaped the structure and function of the human genome. However, questions remain concerning both the frequency and the developmental timing of L1 retrotransposition in vivo and whether the mobility of these retroelements commonly results in insertional and post-insertional mechanisms of genomic injury. Cells exhibiting high rates of L1 retrotransposition might be especially at risk for such injury. We assessed L1 mRNA expression and L1 retrotransposition in two biologically relevant cell types, human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), as well as in control parental human dermal fibroblasts (HDFs). Full-length L1 mRNA and the L1 open reading frame 1-encoded protein (ORF1p) were readily detected in hESCs and iPSCs, but not in HDFs. Sequencing analysis proved the expression of human-specific L1 element mRNAs in iPSCs. Bisulfite sequencing revealed that the increased L1 expression observed in iPSCs correlates with an overall decrease in CpG methylation in the L1 promoter region. Finally, retrotransposition of an engineered human L1 element was ∼10-fold more efficient in iPSCs than in parental HDFs. These findings indicate that somatic cell reprogramming is associated with marked increases in L1 expression and perhaps increases in endogenous L1 retrotransposition, which could potentially impact the genomic integrity of the resultant iPSCs. PMID:21989055

Updated Lagrangian finite element formulations of various biological soft tissue non-linear material models: a comprehensive procedure and review.

PubMed

Townsend, Molly T; Sarigul-Klijn, Nesrin

2016-01-01

Simplified material models are commonly used in computational simulation of biological soft tissue as an approximation of the complicated material response and to minimize computational resources. However, the simulation of complex loadings, such as long-duration tissue swelling, necessitates complex models that are not easy to formulate. This paper strives to offer the updated Lagrangian formulation comprehensive procedure of various non-linear material models for the application of finite element analysis of biological soft tissues including a definition of the Cauchy stress and the spatial tangential stiffness. The relationships between water content, osmotic pressure, ionic concentration and the pore pressure stress of the tissue are discussed with the merits of these models and their applications.

A First Attempt to Bring Computational Biology into Advanced High School Biology Classrooms

PubMed Central

Gallagher, Suzanne Renick; Coon, William; Donley, Kristin; Scott, Abby; Goldberg, Debra S.

2011-01-01

Computer science has become ubiquitous in many areas of biological research, yet most high school and even college students are unaware of this. As a result, many college biology majors graduate without adequate computational skills for contemporary fields of biology. The absence of a computational element in secondary school biology classrooms is of growing concern to the computational biology community and biology teachers who would like to acquaint their students with updated approaches in the discipline. We present a first attempt to correct this absence by introducing a computational biology element to teach genetic evolution into advanced biology classes in two local high schools. Our primary goal was to show students how computation is used in biology and why a basic understanding of computation is necessary for research in many fields of biology. This curriculum is intended to be taught by a computational biologist who has worked with a high school advanced biology teacher to adapt the unit for his/her classroom, but a motivated high school teacher comfortable with mathematics and computing may be able to teach this alone. In this paper, we present our curriculum, which takes into consideration the constraints of the required curriculum, and discuss our experiences teaching it. We describe the successes and challenges we encountered while bringing this unit to high school students, discuss how we addressed these challenges, and make suggestions for future versions of this curriculum.We believe that our curriculum can be a valuable seed for further development of computational activities aimed at high school biology students. Further, our experiences may be of value to others teaching computational biology at this level. Our curriculum can be obtained at http://ecsite.cs.colorado.edu/?page_id=149#biology or by contacting the authors. PMID:22046118

A first attempt to bring computational biology into advanced high school biology classrooms.

PubMed

Gallagher, Suzanne Renick; Coon, William; Donley, Kristin; Scott, Abby; Goldberg, Debra S

2011-10-01

Computer science has become ubiquitous in many areas of biological research, yet most high school and even college students are unaware of this. As a result, many college biology majors graduate without adequate computational skills for contemporary fields of biology. The absence of a computational element in secondary school biology classrooms is of growing concern to the computational biology community and biology teachers who would like to acquaint their students with updated approaches in the discipline. We present a first attempt to correct this absence by introducing a computational biology element to teach genetic evolution into advanced biology classes in two local high schools. Our primary goal was to show students how computation is used in biology and why a basic understanding of computation is necessary for research in many fields of biology. This curriculum is intended to be taught by a computational biologist who has worked with a high school advanced biology teacher to adapt the unit for his/her classroom, but a motivated high school teacher comfortable with mathematics and computing may be able to teach this alone. In this paper, we present our curriculum, which takes into consideration the constraints of the required curriculum, and discuss our experiences teaching it. We describe the successes and challenges we encountered while bringing this unit to high school students, discuss how we addressed these challenges, and make suggestions for future versions of this curriculum.We believe that our curriculum can be a valuable seed for further development of computational activities aimed at high school biology students. Further, our experiences may be of value to others teaching computational biology at this level. Our curriculum can be obtained at http://ecsite.cs.colorado.edu/?page_id=149#biology or by contacting the authors.

Longitudinal Surveys of Australian Youth (LSAY): 1995 Cohort--User Guide. Data Elements B1: Education. Technical Report 49B1

ERIC Educational Resources Information Center

National Centre for Vocational Education Research (NCVER), 2009

2009-01-01

This technical paper contains information about the variables in the LSAY (Longitudinal Surveys of Australian Youth) Y95 cohort data set. It groups each variable into data elements which identifies common variables within and across waves. Information is provided about each data element including its purpose, values, base populations and relevant.…

Student Perceptions of the Cell Biology Laboratory Learning Environment in Four Undergraduate Science Courses in Spain

ERIC Educational Resources Information Center

De Juan, Joaquin; Pérez-Cañaveras, Rosa M.; Segovia, Yolanda; Girela, Jose Luis; Martínez-Ruiz, Noemi; Romero-Rameta, Alejandro; Gómez-Torres, Maria José; Vizcaya-Moreno, M. Flores

2016-01-01

Cell biology is an academic discipline that organises and coordinates the learning of the structure, function and molecular composition of cells in some undergraduate biomedical programs. Besides course content and teaching methodologies, the laboratory environment is considered a key element in the teaching of and learning of cell biology. The…

Evaluation of the Redesign of an Undergraduate Cell Biology Course

ERIC Educational Resources Information Center

McEwen, Laura April; Harris, dik; Schmid, Richard F.; Vogel, Jackie; Western, Tamara; Harrison, Paul

2009-01-01

This article offers a case study of the evaluation of a redesigned and redeveloped laboratory-based cell biology course. The course was a compulsory element of the biology program, but the laboratory had become outdated and was inadequately equipped. With the support of a faculty-based teaching improvement project, the teaching team redesigned the…

Spanish Literacy Investigation Project.

ERIC Educational Resources Information Center

Cook, Jacqueline; Quinones, Anisia

The Spanish Literacy Investigation Project was implemented to identify adult Spanish literacy programs throughout the country, to explore the availability of relevant Spanish literacy teaching methods, to determine relevant elements between Spanish literacy and English as a Second Language (ESL), and to describe a model for incorporating a Spanish…

Metal stable isotopes in low-temperature systems: A primer

USGS Publications Warehouse

Bullen, T.D.; Eisenhauer, A.

2009-01-01

Recent advances in mass spectrometry have allowed isotope scientists to precisely determine stable isotope variations in the metallic elements. Biologically infl uenced and truly inorganic isotope fractionation processes have been demonstrated over the mass range of metals. This Elements issue provides an overview of the application of metal stable isotopes to low-temperature systems, which extend across the borders of several science disciplines: geology, hydrology, biology, environmental science, and biomedicine. Information on instrumentation, fractionation processes, data-reporting terminology, and reference materials presented here will help the reader to better understand this rapidly evolving field.

Biological half-life of gaseous elemental iodine deposited onto rice grains

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

Uchida, S.; Muramatsu, Y.; Sumiya, M.

In order to obtain the biological half-life (Tb) of iodine deposited on rough rice grains, rice plants of four different growing stages--heading, milky, dough, and yellow ripe--were exposed to elemental gaseous iodine. After the exposure, the rough rice samples were collected at different intervals and analyzed for iodine to estimate the value of Tb. The average value of Tb obtained by the experiments at the dough and yellow ripe stages was about 200 d. This value is considerably larger than those for pasture grass and leafy vegetables.

Promoting microbiology education through the iGEM synthetic biology competition.

PubMed

Kelwick, Richard; Bowater, Laura; Yeoman, Kay H; Bowater, Richard P

2015-08-01

Synthetic biology has developed rapidly in the 21st century. It covers a range of scientific disciplines that incorporate principles from engineering to take advantage of and improve biological systems, often applied to specific problems. Methods important in this subject area include the systematic design and testing of biological systems and, here, we describe how synthetic biology projects frequently develop microbiology skills and education. Synthetic biology research has huge potential in biotechnology and medicine, which brings important ethical and moral issues to address, offering learning opportunities about the wider impact of microbiological research. Synthetic biology projects have developed into wide-ranging training and educational experiences through iGEM, the International Genetically Engineered Machines competition. Elements of the competition are judged against specific criteria and teams can win medals and prizes across several categories. Collaboration is an important element of iGEM, and all DNA constructs synthesized by iGEM teams are made available to all researchers through the Registry for Standard Biological Parts. An overview of microbiological developments in the iGEM competition is provided. This review is targeted at educators that focus on microbiology and synthetic biology, but will also be of value to undergraduate and postgraduate students with an interest in this exciting subject area. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The implementation of integrated care: the empirical validation of the Development Model for Integrated Care

PubMed Central

2011-01-01

Background Integrated care is considered as a strategy to improve the delivery, efficiency, client outcomes and satisfaction rates of health care. To integrate the care from multiple providers into a coherent client-focused service, a large number of activities and agreements have to be implemented like streamlining information flows and patient transfers. The Development Model for Integrated care (DMIC) describes nine clusters containing in total 89 elements that contribute to the integration of care. We have empirically validated this model in practice by assessing the relevance, implementation and plans of the elements in three integrated care service settings in The Netherlands: stroke, acute myocardial infarct (AMI), and dementia. Methods Based on the DMIC, a survey was developed for integrated care coordinators. We invited all Dutch stroke and AMI-services, as well as the dementia care networks to participate, of which 84 did (response rate 83%). Data were collected on relevance, presence, and year of implementation of the 89 elements. The data analysis was done by means of descriptive statistics, Chi Square, ANOVA and Kruskal-Wallis H tests. Results The results indicate that the integrated care practice organizations in all three care settings rated the nine clusters and 89 elements of the DMIC as highly relevant. The average number of elements implemented was 50 ± 18, 42 ± 13, and 45 ± 22 for stroke, acute myocardial infarction, and dementia care services, respectively. Although the dementia networks were significantly younger, their numbers of implemented elements were comparable to those of the other services. The analyses of the implementation timelines showed that the older integrated care services had fewer plans for further implementation than the younger ones. Integrated care coordinators stated that the DMIC helped them to assess their integrated care development in practice and supported them in obtaining ideas for expanding their integrated care activities. Conclusions Although the patient composites and the characteristics of the 84 participating integrated care services differed considerably, the results confirm that the clusters and the vast majority of DMIC elements are relevant to all three groups. Therefore, the DMIC can serve as a general quality management tool for integrated care. Applying the model in practice can help in steering further implementations as well as the development of new integrated care practices. PMID:21801428

The implementation of integrated care: the empirical validation of the Development Model for Integrated care.

PubMed

Minkman, Mirella M N; Vermeulen, Robbert P; Ahaus, Kees T B; Huijsman, Robbert

2011-07-30

Integrated care is considered as a strategy to improve the delivery, efficiency, client outcomes and satisfaction rates of health care. To integrate the care from multiple providers into a coherent client-focused service, a large number of activities and agreements have to be implemented like streamlining information flows and patient transfers. The Development Model for Integrated care (DMIC) describes nine clusters containing in total 89 elements that contribute to the integration of care. We have empirically validated this model in practice by assessing the relevance, implementation and plans of the elements in three integrated care service settings in The Netherlands: stroke, acute myocardial infarct (AMI), and dementia. Based on the DMIC, a survey was developed for integrated care coordinators. We invited all Dutch stroke and AMI-services, as well as the dementia care networks to participate, of which 84 did (response rate 83%). Data were collected on relevance, presence, and year of implementation of the 89 elements. The data analysis was done by means of descriptive statistics, Chi Square, ANOVA and Kruskal-Wallis H tests. The results indicate that the integrated care practice organizations in all three care settings rated the nine clusters and 89 elements of the DMIC as highly relevant. The average number of elements implemented was 50 ± 18, 42 ± 13, and 45 ± 22 for stroke, acute myocardial infarction, and dementia care services, respectively. Although the dementia networks were significantly younger, their numbers of implemented elements were comparable to those of the other services. The analyses of the implementation timelines showed that the older integrated care services had fewer plans for further implementation than the younger ones. Integrated care coordinators stated that the DMIC helped them to assess their integrated care development in practice and supported them in obtaining ideas for expanding their integrated care activities. Although the patient composites and the characteristics of the 84 participating integrated care services differed considerably, the results confirm that the clusters and the vast majority of DMIC elements are relevant to all three groups. Therefore, the DMIC can serve as a general quality management tool for integrated care. Applying the model in practice can help in steering further implementations as well as the development of new integrated care practices.

Mechanics of undulatory swimming in a frictional fluid.

PubMed

Ding, Yang; Sharpe, Sarah S; Masse, Andrew; Goldman, Daniel I

2012-01-01

The sandfish lizard (Scincus scincus) swims within granular media (sand) using axial body undulations to propel itself without the use of limbs. In previous work we predicted average swimming speed by developing a numerical simulation that incorporated experimentally measured biological kinematics into a multibody sandfish model. The model was coupled to an experimentally validated soft sphere discrete element method simulation of the granular medium. In this paper, we use the simulation to study the detailed mechanics of undulatory swimming in a "granular frictional fluid" and compare the predictions to our previously developed resistive force theory (RFT) which models sand-swimming using empirically determined granular drag laws. The simulation reveals that the forward speed of the center of mass (CoM) oscillates about its average speed in antiphase with head drag. The coupling between overall body motion and body deformation results in a non-trivial pattern in the magnitude of lateral displacement of the segments along the body. The actuator torque and segment power are maximal near the center of the body and decrease to zero toward the head and the tail. Approximately 30% of the net swimming power is dissipated in head drag. The power consumption is proportional to the frequency in the biologically relevant range, which confirms that frictional forces dominate during sand-swimming by the sandfish. Comparison of the segmental forces measured in simulation with the force on a laterally oscillating rod reveals that a granular hysteresis effect causes the overestimation of the body thrust forces in the RFT. Our models provide detailed testable predictions for biological locomotion in a granular environment.

Translational research in infectious disease: current paradigms and challenges ahead

PubMed Central

Fontana, Judith M.; Alexander, Elizabeth; Salvatore, Mirella

2012-01-01

In recent years, the biomedical community has witnessed a rapid scientific and technological evolution following the development and refinement of high-throughput methodologies. Concurrently and consequentially, the scientific perspective has changed from the reductionist approach of meticulously analyzing the fine details of a single component of biology, to the “holistic” approach of broadmindedly examining the globally interacting elements of biological systems. The emergence of this new way of thinking has brought about a scientific revolution in which genomics, proteomics, metabolomics and other “omics” have become the predominant tools by which large amounts of data are amassed, analyzed and applied to complex questions of biology that were previously unsolvable. This enormous transformation of basic science research and the ensuing plethora of promising data, especially in the realm of human health and disease, have unfortunately not been followed by a parallel increase in the clinical application of this information. On the contrary, the number of new potential drugs in development has been steadily decreasing, suggesting the existence of roadblocks that prevent the translation of promising research into medically relevant therapeutic or diagnostic application. In this paper we will review, in a non-inclusive fashion, several recent scientific advancements in the field of translational research, with a specific focus on how they relate to infectious disease. We will also present a current picture of the limitations and challenges that exist for translational research, as well as ways that have been proposed by the National Institutes of Health to improve the state of this field. PMID:22633095

Mechanics of Undulatory Swimming in a Frictional Fluid

PubMed Central

Ding, Yang; Sharpe, Sarah S.; Masse, Andrew; Goldman, Daniel I.

2012-01-01

The sandfish lizard (Scincus scincus) swims within granular media (sand) using axial body undulations to propel itself without the use of limbs. In previous work we predicted average swimming speed by developing a numerical simulation that incorporated experimentally measured biological kinematics into a multibody sandfish model. The model was coupled to an experimentally validated soft sphere discrete element method simulation of the granular medium. In this paper, we use the simulation to study the detailed mechanics of undulatory swimming in a “granular frictional fluid” and compare the predictions to our previously developed resistive force theory (RFT) which models sand-swimming using empirically determined granular drag laws. The simulation reveals that the forward speed of the center of mass (CoM) oscillates about its average speed in antiphase with head drag. The coupling between overall body motion and body deformation results in a non-trivial pattern in the magnitude of lateral displacement of the segments along the body. The actuator torque and segment power are maximal near the center of the body and decrease to zero toward the head and the tail. Approximately 30% of the net swimming power is dissipated in head drag. The power consumption is proportional to the frequency in the biologically relevant range, which confirms that frictional forces dominate during sand-swimming by the sandfish. Comparison of the segmental forces measured in simulation with the force on a laterally oscillating rod reveals that a granular hysteresis effect causes the overestimation of the body thrust forces in the RFT. Our models provide detailed testable predictions for biological locomotion in a granular environment. PMID:23300407

Topological side-chain classification of beta-turns: ideal motifs for peptidomimetic development.

PubMed

Tran, Tran Trung; McKie, Jim; Meutermans, Wim D F; Bourne, Gregory T; Andrews, Peter R; Smythe, Mark L

2005-08-01

Beta-turns are important topological motifs for biological recognition of proteins and peptides. Organic molecules that sample the side chain positions of beta-turns have shown broad binding capacity to multiple different receptors, for example benzodiazepines. Beta-turns have traditionally been classified into various types based on the backbone dihedral angles (phi2, psi2, phi3 and psi3). Indeed, 57-68% of beta-turns are currently classified into 8 different backbone families (Type I, Type II, Type I', Type II', Type VIII, Type VIa1, Type VIa2 and Type VIb and Type IV which represents unclassified beta-turns). Although this classification of beta-turns has been useful, the resulting beta-turn types are not ideal for the design of beta-turn mimetics as they do not reflect topological features of the recognition elements, the side chains. To overcome this, we have extracted beta-turns from a data set of non-homologous and high-resolution protein crystal structures. The side chain positions, as defined by C(alpha)-C(beta) vectors, of these turns have been clustered using the kth nearest neighbor clustering and filtered nearest centroid sorting algorithms. Nine clusters were obtained that cluster 90% of the data, and the average intra-cluster RMSD of the four C(alpha)-C(beta) vectors is 0.36. The nine clusters therefore represent the topology of the side chain scaffold architecture of the vast majority of beta-turns. The mean structures of the nine clusters are useful for the development of beta-turn mimetics and as biological descriptors for focusing combinatorial chemistry towards biologically relevant topological space.

Optical fiber tips for biological applications: From light confinement, biosensing to bioparticles manipulation.

PubMed

Paiva, Joana S; Jorge, Pedro A S; Rosa, Carla C; Cunha, João P S

2018-05-01

The tip of an optical fiber has been considered an attractive platform in Biology. The simple cleaved end of an optical fiber can be machined, patterned and/or functionalized, acquiring unique properties enabling the exploitation of novel optical phenomena. Prompted by the constant need to measure and manipulate nanoparticles, the invention of the Scanning Near-field Optical Microscopy (SNOM) triggered the optimization and development of novel fiber tip microfabrication methods. In fact, the fiber tip was soon considered a key element in SNOM by confining light to sufficiently small extensions, challenging the diffraction limit. As result and in consequence of the newly proposed "Lab On Tip" concept, several geometries of fiber tips were applied in three main fields: imaging (in Microscopy/Spectroscopy), biosensors and micromanipulation (Optical Fiber Tweezers, OFTs). These are able to exert forces on microparticles, trap and manipulate them for relevant applications, as biomolecules mechanical study or protein aggregates unfolding. This review presents an overview of the main achievements, most impactful studies and limitations of fiber tip-based configurations within the above three fields, along the past 10 years. OFTs could be in future a valuable tool for studying several cellular phenomena such as neurodegeneration caused by abnormal protein fibrils or manipulating organelles within cells. This could contribute to understand the mechanisms of some diseases or biophenomena, as the axonal growth in neurons. To the best of our knowledge, no other review article has so far provided such a broad view. Despite of the limitations, fiber tips have key roles in Biology/Medicine. Copyright © 2018 Elsevier B.V. All rights reserved.

Autofluorescence of atmospheric bioaerosols - fluorescent biomolecules and potential interferences

NASA Astrophysics Data System (ADS)

Pöhlker, C.; Huffman, J. A.; Pöschl, U.

2012-01-01

Primary biological aerosol particles (PBAP) are an important subset of air particulate matter with a substantial contribution to the organic aerosol fraction and potentially strong effects on public health and climate. Recent progress has been made in PBAP quantification by utilizing real-time bioaerosol detectors based on the principle that specific organic molecules of biological origin such as proteins, coenzymes, cell wall compounds and pigments exhibit intrinsic fluorescence. The properties of many fluorophores have been well documented, but it is unclear which are most relevant for detection of atmospheric PBAP. The present study provides a systematic synthesis of literature data on potentially relevant biological fluorophores. We analyze and discuss their relative importance for the detection of fluorescent biological aerosol particles (FBAP) by online instrumentation for atmospheric measurements such as the ultraviolet aerodynamic particle sizer (UV-APS) or the wide issue bioaerosol sensor (WIBS). In addition, we provide new laboratory measurement data for selected compounds using bench-top fluorescence spectroscopy. Relevant biological materials were chosen for comparison with existing literature data and to fill in gaps of understanding. The excitation-emission matrices (EEM) exhibit pronounced peaks at excitation wavelengths of ~280 nm and ~360 nm, confirming the suitability of light sources used for online detection of FBAP. They also show, however, that valuable information is missed by instruments that do not record full emission spectra at multiple wavelengths of excitation, and co-occurrence of multiple fluorophores within a detected sample will likely confound detailed molecular analysis. Selected non-biological materials were also analyzed to assess their possible influence on FBAP detection and generally exhibit only low levels of background-corrected fluorescent emission. This study strengthens the hypothesis that ambient supermicron particle fluorescence in wavelength ranges used for most FBAP instruments is likely to be dominated by biological material and that such instrumentation is able to discriminate between FBAP and non-biological material in many situations. More detailed follow-up studies on single particle fluorescence are still required to reduce these uncertainties further, however.

Autofluorescence of atmospheric bioaerosols - fluorescent biomolecules and potential interferences

NASA Astrophysics Data System (ADS)

Pöhlker, C.; Huffman, J. A.; Pöschl, U.

2011-09-01

Primary biological aerosol particles (PBAP) are an important subset of air particulate matter with a substantial contribution to the organic aerosol fraction and potentially strong effects on public health and climate. Recent progress has been made in PBAP quantification by utilizing real-time bioaerosol detectors based on the principle that specific organic molecules of biological origin such as proteins, coenzymes, cell wall compounds and pigments exhibit intrinsic fluorescence. The properties of many fluorophores have been well documented, but it is unclear which are most relevant for detection of atmospheric PBAP. The present study provides a systematic synthesis of literature data on potentially relevant biological fluorophores. We analyze and discuss their relative importance for the detection of fluorescent biological aerosol particles (FBAP) by online instrumentation for atmospheric measurements such as the ultraviolet aerodynamic particle sizer (UV-APS) or the wide issue bioaerosol sensor (WIBS). In addition, we provide new laboratory measurement data for selected compounds using bench-top fluorescence spectroscopy. Relevant biological materials were chosen for comparison with existing literature data and to fill in gaps of understanding. The excitation-emission matrices (EEM) exhibit pronounced peaks at excitation wavelengths of ~280 nm and ~360 nm, confirming the suitability of light sources used for online detection of FBAP. They also show, however, that valuable information is missed by instruments that do not record full emission spectra at multiple wavelengths of excitation, and co-occurrence of multiple fluorophores within a detected sample will likely confound detailed molecular analysis. Selected non-biological materials were also analyzed to assess their possible influence on FBAP detection and generally exhibit only low levels of background-corrected fluorescent emission. This study strengthens the hypothesis that ambient supermicron particle fluorescence in wavelength ranges used for most FBAP instruments is likely to be dominated by biological material and that such instrumentation is able to discriminate between FBAP and non-biological material in many situations. More detailed follow-up studies on single particle fluorescence are still required to reduce these uncertainties further, however.

A bridge from physics to biology.

PubMed

Preparata, Giuliano

2010-01-01

Through molecular biology, the 'atomistic paradigm' tries to remove from the analysis of living matter every element of what appears as the distinguishing character of the chain of the biological processes: their cooperative, collective aspects. Living matter appears, on the contrary, governed by Quantum Field Theory (QFT), spontaneously creating order when the thermodynamical conditions are right. 'Electrodynamical coherence' (EC) is the most promising hint for the existence of a bridge between Physics and Biology.

History of the molecular biology of cytomegaloviruses.

PubMed

Stinski, Mark F

2014-01-01

The history of the molecular biology of cytomegaloviruses from the purification of the virus and the viral DNA to the cloning and expression of the viral genes is reviewed. A key genetic element of cytomegalovirus (the CMV promoter) contributed to our understanding of eukaryotic cell molecular biology and to the development of lifesaving therapeutic proteins. The study of the molecular biology of cytomegaloviruses also contributed to the development of antivirals to control the viral infection.

BioMetals: a historical and personal perspective.

PubMed

Silver, Simon

2011-06-01

Understanding of BioMetals developed basically from a starting point about 60 years ago to current mechanistic understanding of the biological behavior of many metal ions from protein structural and functional studies. Figure 1 shows a Biochemical Periodic Table, element by element, with requirements, roles and biochemistry of the specific ions indicated. With few exceptions, the biology is of the ions formed and not of the elemental state of each. Early BioMetals efforts defined nutritional growth needs for animals, plants and microbes for inorganic "macro-nutrients" such as magnesium, calcium, potassium, sodium, and phosphate and of "micronutrients" such as copper, iron, manganese and zinc. Surprises came early with regard to microbes, for example the finding that Escherichia coli (then and now the standard microbial model) grows happily in the apparent total absence of calcium, sodium, and chloride, which are certainly major animal nutrients. Some elements such as mercury and arsenic are never required by living cells, but are always toxic, often at very low levels. Therefore, the division into nutrient elements and toxic elements came soon. For most inorganic nutrients, excessive amounts can be toxic as well, for example for copper and iron.

Toxicological importance of human biomonitoring of metallic and metalloid elements in different biological samples.

PubMed

Gil, F; Hernández, A F

2015-06-01

Human biomonitoring has become an important tool for the assessment of internal doses of metallic and metalloid elements. These elements are of great significance because of their toxic properties and wide distribution in environmental compartments. Although blood and urine are the most used and accepted matrices for human biomonitoring, other non-conventional samples (saliva, placenta, meconium, hair, nails, teeth, breast milk) may have practical advantages and would provide additional information on health risk. Nevertheless, the analysis of these compounds in biological matrices other than blood and urine has not yet been accepted as a useful tool for biomonitoring. The validation of analytical procedures is absolutely necessary for a proper implementation of non-conventional samples in biomonitoring programs. However, the lack of reliable and useful analytical methodologies to assess exposure to metallic elements, and the potential interference of external contamination and variation in biological features of non-conventional samples are important limitations for setting health-based reference values. The influence of potential confounding factors on metallic concentration should always be considered. More research is needed to ascertain whether or not non-conventional matrices offer definitive advantages over the traditional samples and to broaden the available database for establishing worldwide accepted reference values in non-exposed populations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pushing the size limit of de novo structure ensemble prediction guided by sparse SDSL-EPR restraints to 200 residues: The monomeric and homodimeric forms of BAX

PubMed Central

Fischer, Axel W.; Bordignon, Enrica; Bleicken, Stephanie; García-Sáez, Ana J.; Jeschke, Gunnar; Meiler, Jens

2016-01-01

Structure determination remains a challenge for many biologically important proteins. In particular, proteins that adopt multiple conformations often evade crystallization in all biologically relevant states. Although computational de novo protein folding approaches often sample biologically relevant conformations, the selection of the most accurate model for different functional states remains a formidable challenge, in particular, for proteins with more than about 150 residues. Electron paramagnetic resonance (EPR) spectroscopy can obtain limited structural information for proteins in well-defined biological states and thereby assist in selecting biologically relevant conformations. The present study demonstrates that de novo folding methods are able to accurately sample the folds of 192-residue long soluble monomeric Bcl-2-associated X protein (BAX). The tertiary structures of the monomeric and homodimeric forms of BAX were predicted using the primary structure as well as 25 and 11 EPR distance restraints, respectively. The predicted models were subsequently compared to respective NMR/X-ray structures of BAX. EPR restraints improve the protein-size normalized root-mean-square-deviation (RMSD100) of the most accurate models with respect to the NMR/crystal structure from 5.9 Å to 3.9 Å and from 5.7 Å to 3.3 Å, respectively. Additionally, the model discrimination is improved, which is demonstrated by an improvement of the enrichment from 5% to 15% and from 13% to 21%, respectively. PMID:27129417

Single cell biology beyond the era of antibodies: relevance, challenges, and promises in biomedical research.

PubMed

Abraham, Parvin; Maliekal, Tessy Thomas

2017-04-01

Research of the past two decades has proved the relevance of single cell biology in basic research and translational medicine. Successful detection and isolation of specific subsets is the key to understand their functional heterogeneity. Antibodies are conventionally used for this purpose, but their relevance in certain contexts is limited. In this review, we discuss some of these contexts, posing bottle neck for different fields of biology including biomedical research. With the advancement of chemistry, several methods have been introduced to overcome these problems. Even though microfluidics and microraft array are newer techniques exploited for single cell biology, fluorescence-activated cell sorting (FACS) remains the gold standard technique for isolation of cells for many biomedical applications, like stem cell therapy. Here, we present a comprehensive and comparative account of some of the probes that are useful in FACS. Further, we illustrate how these techniques could be applied in biomedical research. It is postulated that intracellular molecular markers like nucleostemin (GNL3), alkaline phosphatase (ALPL) and HIRA can be used for improving the outcome of cardiac as well as bone regeneration. Another field that could utilize intracellular markers is diagnostics, and we propose the use of specific peptide nucleic acid probes (PNPs) against certain miRNAs for cancer surgical margin prediction. The newer techniques for single cell biology, based on intracellular molecules, will immensely enhance the repertoire of possible markers for the isolation of cell types useful in biomedical research.

Comprehensive inventory of protein complexes in the Protein Data Bank from consistent classification of interfaces.

PubMed

Bordner, Andrew J; Gorin, Andrey A

2008-05-12

Protein-protein interactions are ubiquitous and essential for all cellular processes. High-resolution X-ray crystallographic structures of protein complexes can reveal the details of their function and provide a basis for many computational and experimental approaches. Differentiation between biological and non-biological contacts and reconstruction of the intact complex is a challenging computational problem. A successful solution can provide additional insights into the fundamental principles of biological recognition and reduce errors in many algorithms and databases utilizing interaction information extracted from the Protein Data Bank (PDB). We have developed a method for identifying protein complexes in the PDB X-ray structures by a four step procedure: (1) comprehensively collecting all protein-protein interfaces; (2) clustering similar protein-protein interfaces together; (3) estimating the probability that each cluster is relevant based on a diverse set of properties; and (4) combining these scores for each PDB entry in order to predict the complex structure. The resulting clusters of biologically relevant interfaces provide a reliable catalog of evolutionary conserved protein-protein interactions. These interfaces, as well as the predicted protein complexes, are available from the Protein Interface Server (PInS) website (see Availability and requirements section). Our method demonstrates an almost two-fold reduction of the annotation error rate as evaluated on a large benchmark set of complexes validated from the literature. We also estimate relative contributions of each interface property to the accurate discrimination of biologically relevant interfaces and discuss possible directions for further improving the prediction method.

Biological Weapons -- Still a Relevant Threat

DTIC Science & Technology

2012-03-22

destruction in general, and biological weapons in particular. The IHS Janes: Defence and Security Intelligence & Analysis website notes that a number of...responder capabilities, and intelligence agency inputs. There needs, as well, to be continued research and development of sensor technologies, which...Mass Destruction – Radiological, Chemical and Biological,‖ 109 10 Mark, J. Carson; Taylor, Theodore; Eyster, Eugene; Maraman, William; Wechsler