Materiomics: biological protein materials, from nano to macro.

PubMed

Cranford, Steven; Buehler, Markus J

2010-11-12

Materiomics is an emerging field of science that provides a basis for multiscale material system characterization, inspired in part by natural, for example, protein-based materials. Here we outline the scope and explain the motivation of the field of materiomics, as well as demonstrate the benefits of a materiomic approach in the understanding of biological and natural materials as well as in the design of de novo materials. We discuss recent studies that exemplify the impact of materiomics - discovering Nature's complexity through a materials science approach that merges concepts of material and structure throughout all scales and incorporates feedback loops that facilitate sensing and resulting structural changes at multiple scales. The development and application of materiomics is illustrated for the specific case of protein-based materials, which constitute the building blocks of a variety of biological systems such as tendon, bone, skin, spider silk, cells, and tissue, as well as natural composite material systems (a combination of protein-based and inorganic constituents) such as nacre and mollusk shells, and other natural multiscale systems such as cellulose-based plant and wood materials. An important trait of these materials is that they display distinctive hierarchical structures across multiple scales, where molecular details are exhibited in macroscale mechanical responses. Protein materials are intriguing examples of materials that balance multiple tasks, representing some of the most sustainable material solutions that integrate structure and function despite severe limitations in the quality and quantity of material building blocks. However, up until now, our attempts to analyze and replicate Nature's materials have been hindered by our lack of fundamental understanding of these materials' intricate hierarchical structures, scale-bridging mechanisms, and complex material components that bestow protein-based materials their unique properties. Recent advances in analytical tools and experimental methods allow a holistic view of such a hierarchical biological material system. The integration of these approaches and amalgamation of material properties at all scale levels to develop a complete description of a material system falls within the emerging field of materiomics. Materiomics is the result of the convergence of engineering and materials science with experimental and computational biology in the context of natural and synthetic materials. Through materiomics, fundamental advances in our understanding of structure-property-process relations of biological systems contribute to the mechanistic understanding of certain diseases and facilitate the development of novel biological, biologically inspired, and completely synthetic materials for applications in medicine (biomaterials), nanotechnology, and engineering.

Multiple Roles of Photosynthetic and Sunscreen Pigments in Cyanobacteria Focusing on the Oxidative Stress

PubMed Central

Wada, Naoki; Sakamoto, Toshio; Matsugo, Seiichi

2013-01-01

Cyanobacteria have two types of sunscreen pigments, scytonemin and mycosporine-like amino acids (MAAs). These secondary metabolites are thought to play multiple roles against several environmental stresses such as UV radiation and desiccation. Not only the large molar absorption coefficients of these sunscreen pigments, but also their antioxidative properties may be necessary for the protection of biological molecules against the oxidative damages induced by UV radiation. The antioxidant activity and vitrification property of these pigments are thought to be requisite for the desiccation and rehydration processes in anhydrobiotes. In this review, the multiple roles of photosynthetic pigments and sunscreen pigments on stress resistance, especially from the viewpoint of their structures, biosynthetic pathway, and in vitro studies of their antioxidant activity, will be discussed. PMID:24958001

Designing multiple ligands - medicinal chemistry strategies and challenges.

PubMed

Morphy, Richard; Rankovic, Zoran

2009-01-01

It has been widely recognised over the recent years that parallel modulation of multiple biological targets can be beneficial for treatment of diseases with complex etiologies such as cancer asthma, and psychiatric disease. In this article, current strategies for the generation of ligands with a specific multi-target profile (designed multiple ligands or DMLs) are described and a number of illustrative example are given. Designing multiple ligands is frequently a challenging endeavour for medicinal chemists, with the need to appropriately balance affinity for 2 or more targets whilst obtaining physicochemical and pharmacokinetic properties that are consistent with the administration of an oral drug. Given that the properties of DMLs are influenced to a large extent by the proteomic superfamily to which the targets belong and the lead generation strategy that is pursued, an early assessment of the feasibility of any given DML project is essential.

The genus Machaerium (Fabaceae): taxonomy, phytochemistry, traditional uses and biological activities.

PubMed

Amen, Yhiya M; Marzouk, Amani M; Zaghloul, Mona G; Afifi, Mohamed S

2015-01-01

Machaerium, in the family Fabaceae, predominantly is a genus of a Neotropical distribution of trees, shrubs, and lianas occurring from southern Mexico to Brazil and northern Argentina and as far as South America. Several Machaerium species are widely used in traditional medicine and are considered to have multiple medicinal properties. This review aims to provide up-to-date and comprehensive information on the taxonomy, phytochemistry, traditional uses and biological activities of plants in the genus Machaerium.

Advances in chemical labeling of proteins in living cells.

PubMed

Yan, Qi; Bruchez, Marcel P

2015-04-01

The pursuit of quantitative biological information via imaging requires robust labeling approaches that can be used in multiple applications and with a variety of detectable colors and properties. In addition to conventional fluorescent proteins, chemists and biologists have come together to provide a range of approaches that combine dye chemistry with the convenience of genetic targeting. This hybrid-tagging approach amalgamates the rational design of properties available through synthetic dye chemistry with the robust biological targeting available with genetic encoding. In this review, we discuss the current range of approaches that have been exploited for dye targeting or for targeting and activation and some of the recent applications that are uniquely permitted by these hybrid-tagging approaches.

Intrinsic hierarchical structural imperfections in a natural ceramic of bivalve shell with distinctly graded properties

PubMed Central

Jiao, Da; Liu, Zengqian; Zhang, Zhenjun; Zhang, Zhefeng

2015-01-01

Despite the extensive investigation on the structure of natural biological materials, insufficient attention has been paid to the structural imperfections by which the mechanical properties of synthetic materials are dominated. In this study, the structure of bivalve Saxidomus purpuratus shell has been systematically characterized quantitatively on multiple length scales from millimeter to sub-nanometer. It is revealed that hierarchical imperfections are intrinsically involved in the crossed-lamellar structure of the shell despite its periodically packed platelets. In particular, various favorable characters which are always pursued in synthetic materials, e.g. nanotwins and low-angle misorientations, have been incorporated herein. The possible contributions of these imperfections to mechanical properties are further discussed. It is suggested that the imperfections may serve as structural adaptations, rather than detrimental defects in the real sense, to help improve the mechanical properties of natural biological materials. This study may aid in understanding the optimizing strategies of structure and properties designed by nature, and accordingly, provide inspiration for the design of synthetic materials. PMID:26198844

Intrinsic hierarchical structural imperfections in a natural ceramic of bivalve shell with distinctly graded properties.

PubMed

Jiao, Da; Liu, Zengqian; Zhang, Zhenjun; Zhang, Zhefeng

2015-07-22

Despite the extensive investigation on the structure of natural biological materials, insufficient attention has been paid to the structural imperfections by which the mechanical properties of synthetic materials are dominated. In this study, the structure of bivalve Saxidomus purpuratus shell has been systematically characterized quantitatively on multiple length scales from millimeter to sub-nanometer. It is revealed that hierarchical imperfections are intrinsically involved in the crossed-lamellar structure of the shell despite its periodically packed platelets. In particular, various favorable characters which are always pursued in synthetic materials, e.g. nanotwins and low-angle misorientations, have been incorporated herein. The possible contributions of these imperfections to mechanical properties are further discussed. It is suggested that the imperfections may serve as structural adaptations, rather than detrimental defects in the real sense, to help improve the mechanical properties of natural biological materials. This study may aid in understanding the optimizing strategies of structure and properties designed by nature, and accordingly, provide inspiration for the design of synthetic materials.

PARTIAL LEAST SQUARE ANALYSES FOR ASSOCIATION OF LANDSCAPE METRICS WITH WATER BIOLOGICAL AND CHEMICAL PROPERTIES IN THE SAVANNAH RIVER BASIN

EPA Science Inventory

Surface water quality is related to conditions in the surrounding geophysical environment, including soils, landcover, and anthropogenic activities. A number of statistical methods may be used to analyze and explore relationships among variables. Single-, multiple- and multivaria...

Ellagic Acid: A Logical Lead for Drug Development?

PubMed

Shakeri, Abolfazl; Zirak, Mohammad Reza; Sahebkar, Amirhossein

2018-01-01

Naturally occurring polyphenols are the subject of increasing attention due to their potent antioxidant activity and their marked effects on the prevention of various oxidative stress-associated diseases such as cancer. Ellagic acid (EA) is an herbal polyphenol that is structurally a condensed dimer of gallic acid. This review aims to provide a comprehensive and updated overview on the biological activities of EA and potential therapeutic applications. EA is found in fruits and nuts, either in the combined form with hexahydroxydiphenic acid or in the bound form (ellagitannins). EA exhibits many biological properties such as antioxidant, anti-diabetic, anticancer and apoptosis-inducing activities. These biological and pharmacological properties are relevant to the treatment of several human diseases. Owing to its multiple mechanisms of action, EA represents a potential therapeutic agent against human diseases particularly cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Emergent properties of interacting populations of spiking neurons.

PubMed

Cardanobile, Stefano; Rotter, Stefan

2011-01-01

Dynamic neuronal networks are a key paradigm of increasing importance in brain research, concerned with the functional analysis of biological neuronal networks and, at the same time, with the synthesis of artificial brain-like systems. In this context, neuronal network models serve as mathematical tools to understand the function of brains, but they might as well develop into future tools for enhancing certain functions of our nervous system. Here, we present and discuss our recent achievements in developing multiplicative point processes into a viable mathematical framework for spiking network modeling. The perspective is that the dynamic behavior of these neuronal networks is faithfully reflected by a set of non-linear rate equations, describing all interactions on the population level. These equations are similar in structure to Lotka-Volterra equations, well known by their use in modeling predator-prey relations in population biology, but abundant applications to economic theory have also been described. We present a number of biologically relevant examples for spiking network function, which can be studied with the help of the aforementioned correspondence between spike trains and specific systems of non-linear coupled ordinary differential equations. We claim that, enabled by the use of multiplicative point processes, we can make essential contributions to a more thorough understanding of the dynamical properties of interacting neuronal populations.

Emergent Properties of Interacting Populations of Spiking Neurons

PubMed Central

Cardanobile, Stefano; Rotter, Stefan

2011-01-01

Dynamic neuronal networks are a key paradigm of increasing importance in brain research, concerned with the functional analysis of biological neuronal networks and, at the same time, with the synthesis of artificial brain-like systems. In this context, neuronal network models serve as mathematical tools to understand the function of brains, but they might as well develop into future tools for enhancing certain functions of our nervous system. Here, we present and discuss our recent achievements in developing multiplicative point processes into a viable mathematical framework for spiking network modeling. The perspective is that the dynamic behavior of these neuronal networks is faithfully reflected by a set of non-linear rate equations, describing all interactions on the population level. These equations are similar in structure to Lotka-Volterra equations, well known by their use in modeling predator-prey relations in population biology, but abundant applications to economic theory have also been described. We present a number of biologically relevant examples for spiking network function, which can be studied with the help of the aforementioned correspondence between spike trains and specific systems of non-linear coupled ordinary differential equations. We claim that, enabled by the use of multiplicative point processes, we can make essential contributions to a more thorough understanding of the dynamical properties of interacting neuronal populations. PMID:22207844

Sarmentine, a natural herbicide from Piper species with multiple herbicide mechanisms of action

USDA-ARS?s Scientific Manuscript database

Sarmentine, 1-(1-pyrrolidinyl)-(2E,4E)-2,4-decadien-1-one, is a natural amide isolated from the fruits of Piper species. The compound has a number of interesting biological properties, including its broad-spectrum activity on weeds as a contact herbicide. Initial studies highlighted a similarity in ...

The Mayo Innovation Scholars Program: Undergraduates Explore the Science and Economics of Medical Innovations

ERIC Educational Resources Information Center

Pellegrini, John J.; Jansen, Elizabeth

2013-01-01

The Mayo Innovation Scholars Program introduces undergraduates to technology transfer in biomedical sciences by having teams of students from multiple disciplines (e.g., biology, chemistry, economics, and business) analyze inventions in development at the Mayo Clinic. Over 6 months, teams consult with inventors, intellectual property experts, and…

Mobility as an emergent property of biological organization: Insights from experimental evolution.

PubMed

Wallace, Ian J; Garland, Theodore

2016-05-06

Anthropologists accept that mobility is a critical dimension of human culture, one that links economy, technology, and social relations. Less often acknowledged is that mobility depends on complex and dynamic interactions between multiple levels of our biological organization, including anatomy, physiology, neurobiology, and genetics. Here, we describe a novel experimental approach to examining the biological foundations of mobility, using mice from a long-term artificial selection experiment for high levels of voluntary exercise on wheels. In this experiment, mice from selectively bred lines have evolved to run roughly three times as far per day as those from nonselected control lines. We consider three insights gleaned from this experiment as foundational principles for the study of mobility from the perspective of biological evolution. First, an evolutionary change in mobility will necessarily be associated with alterations in biological traits both directly and indirectly connected to mobility. Second, changing mobility will result in trade-offs and constraints among some of the affected traits. Third, multiple solutions exist to altering mobility, so that various combinations of adjustments to traits linked with mobility can achieve the same overall behavioral outcome. We suggest that anthropological knowledge of variation in human mobility might be improved by greater research attention to its biological dimensions. © 2016 Wiley Periodicals, Inc.

On some properties of bone functional adaptation phenomenon useful in mechanical design.

PubMed

Nowak, Michał

2010-01-01

The paper discusses some unique properties of trabecular bone functional adaptation phenomenon, useful in mechanical design. On the basis of the biological process observations and the principle of constant strain energy density on the surface of the structure, the generic structural optimisation system has been developed. Such approach allows fulfilling mechanical theorem for the stiffest design, comprising the optimisations of size, shape and topology, using the concepts known from biomechanical studies. Also the biomimetic solution of multiple load problems is presented.

Multidimensional proteomics for cell biology.

PubMed

Larance, Mark; Lamond, Angus I

2015-05-01

The proteome is a dynamic system in which each protein has interconnected properties - dimensions - that together contribute to the phenotype of a cell. Measuring these properties has proved challenging owing to their diversity and dynamic nature. Advances in mass spectrometry-based proteomics now enable the measurement of multiple properties for thousands of proteins, including their abundance, isoform expression, turnover rate, subcellular localization, post-translational modifications and interactions. Complementing these experimental developments are new data analysis, integration and visualization tools as well as data-sharing resources. Together, these advances in the multidimensional analysis of the proteome are transforming our understanding of various cellular and physiological processes.

Cellular and Molecular Actions of Methylene Blue in the Nervous System

PubMed Central

Oz, Murat; Lorke, Dietrich E.; Hasan, Mohammed; Petroianu, George A.

2010-01-01

Methylene Blue (MB), following its introduction to biology in the 19th century by Ehrlich, has found uses in various areas of medicine and biology. At present, MB is the first line of treatment in methemoglobinemias, is used frequently in the treatment of ifosfamide-induced encephalopathy, and is routinely employed as a diagnostic tool in surgical procedures. Furthermore, recent studies suggest that MB has beneficial effects in Alzheimer's disease and memory improvement. Although the modulation of the cGMP pathway is considered the most significant effect of MB, mediating its pharmacological actions, recent studies indicate that it has multiple cellular and molecular targets. In the majority of cases, biological effects and clinical applications of MB are dictated by its unique physicochemical properties including its planar structure, redox chemistry, ionic charges, and light spectrum characteristics. In this review article, these physicochemical features and the actions of MB on multiple cellular and molecular targets are discussed with regard to their relevance to the nervous system. PMID:19760660

Osthole: A Review on Its Bioactivities, Pharmacological Properties, and Potential as Alternative Medicine

PubMed Central

Zhang, Zhong-Rong; Leung, Wing Nang; Cheung, Ho Yee; Chan, Chun Wai

2015-01-01

This paper reviews the latest understanding of biological and pharmacological properties of osthole (7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one), a natural product found in several medicinal plants such as Cnidium monnieri and Angelica pubescens. In vitro and in vivo experimental results have revealed that osthole demonstrates multiple pharmacological actions including neuroprotective, osteogenic, immunomodulatory, anticancer, hepatoprotective, cardiovascular protective, and antimicrobial activities. In addition, pharmacokinetic studies showed osthole uptake and utilization are fast and efficient in body. Moreover, the mechanisms of multiple pharmacological activities of osthole are very likely related to the modulatory effect on cyclic adenosine monophosphate (cAMP) and cyclic adenosine monophosphate (cGMP) level, though some mechanisms remain unclear. This review aims to summarize the pharmacological properties of osthole and give an overview of the underlying mechanisms, which showcase its potential as a multitarget alternative medicine. PMID:26246843

Integration of functional myotubes with a Bio-MEMS device for non-invasive interrogation.

PubMed

Wilson, Kerry; Molnar, Peter; Hickman, James

2007-07-01

We have developed a biological micro-electromechanical system (Bio-MEMS) device consisting of surface-modified microfabricated silicon cantilevers and an AFM detection apparatus for the study of cultured myotubes. With this system we are able to selectively stimulate the myotubes as well as report on a variety of physiological properties of the myotubes in real time and in a high-throughput manner. This system will serve as the foundation for future work integrating multiple tissue types for the creation of Bio-MEMS analogues of complex tissues and biological circuits.

Small RNA biology is systems biology.

PubMed

Jost, Daniel; Nowojewski, Andrzej; Levine, Erel

2011-01-01

During the last decade small regulatory RNA (srRNA) emerged as central players in the regulation of gene expression in all kingdoms of life. Multiple pathways for srRNA biogenesis and diverse mechanisms of gene regulation may indicate that srRNA regulation evolved independently multiple times. However, small RNA pathways share numerous properties, including the ability of a single srRNA to regulate multiple targets. Some of the mechanisms of gene regulation by srRNAs have significant effect on the abundance of free srRNAs that are ready to interact with new targets. This results in indirect interactions among seemingly unrelated genes, as well as in a crosstalk between different srRNA pathways. Here we briefly review and compare the major srRNA pathways, and argue that the impact of srRNA is always at the system level. We demonstrate how a simple mathematical model can ease the discussion of governing principles. To demonstrate these points we review a few examples from bacteria and animals.

Towards physical principles of biological evolution

NASA Astrophysics Data System (ADS)

Katsnelson, Mikhail I.; Wolf, Yuri I.; Koonin, Eugene V.

2018-03-01

Biological systems reach organizational complexity that far exceeds the complexity of any known inanimate objects. Biological entities undoubtedly obey the laws of quantum physics and statistical mechanics. However, is modern physics sufficient to adequately describe, model and explain the evolution of biological complexity? Detailed parallels have been drawn between statistical thermodynamics and the population-genetic theory of biological evolution. Based on these parallels, we outline new perspectives on biological innovation and major transitions in evolution, and introduce a biological equivalent of thermodynamic potential that reflects the innovation propensity of an evolving population. Deep analogies have been suggested to also exist between the properties of biological entities and processes, and those of frustrated states in physics, such as glasses. Such systems are characterized by frustration whereby local state with minimal free energy conflict with the global minimum, resulting in ‘emergent phenomena’. We extend such analogies by examining frustration-type phenomena, such as conflicts between different levels of selection, in biological evolution. These frustration effects appear to drive the evolution of biological complexity. We further address evolution in multidimensional fitness landscapes from the point of view of percolation theory and suggest that percolation at level above the critical threshold dictates the tree-like evolution of complex organisms. Taken together, these multiple connections between fundamental processes in physics and biology imply that construction of a meaningful physical theory of biological evolution might not be a futile effort. However, it is unrealistic to expect that such a theory can be created in one scoop; if it ever comes to being, this can only happen through integration of multiple physical models of evolutionary processes. Furthermore, the existing framework of theoretical physics is unlikely to suffice for adequate modeling of the biological level of complexity, and new developments within physics itself are likely to be required.

Direct measurement of local material properties within living embryonic tissues

NASA Astrophysics Data System (ADS)

Serwane, Friedhelm; Mongera, Alessandro; Rowghanian, Payam; Kealhofer, David; Lucio, Adam; Hockenbery, Zachary; Campàs, Otger

The shaping of biological matter requires the control of its mechanical properties across multiple scales, ranging from single molecules to cells and tissues. Despite their relevance, measurements of the mechanical properties of sub-cellular, cellular and supra-cellular structures within living embryos pose severe challenges to existing techniques. We have developed a technique that uses magnetic droplets to measure the mechanical properties of complex fluids, including in situ and in vivo measurements within living embryos ,across multiple length and time scales. By actuating the droplets with magnetic fields and recording their deformation we probe the local mechanical properties, at any length scale we choose by varying the droplets' diameter. We use the technique to determine the subcellular mechanics of individual blastomeres of zebrafish embryos, and bridge the gap to the tissue scale by measuring the local viscosity and elasticity of zebrafish embryonic tissues. Using this technique, we show that embryonic zebrafish tissues are viscoelastic with a fluid-like behavior at long time scales. This technique will enable mechanobiology and mechano-transduction studies in vivo, including the study of diseases correlated with tissue stiffness, such as cancer.

Oscillations and Multiple Equilibria in Microvascular Blood Flow.

PubMed

Karst, Nathaniel J; Storey, Brian D; Geddes, John B

2015-07-01

We investigate the existence of oscillatory dynamics and multiple steady-state flow rates in a network with a simple topology and in vivo microvascular blood flow constitutive laws. Unlike many previous analytic studies, we employ the most biologically relevant models of the physical properties of whole blood. Through a combination of analytic and numeric techniques, we predict in a series of two-parameter bifurcation diagrams a range of dynamical behaviors, including multiple equilibria flow configurations, simple oscillations in volumetric flow rate, and multiple coexistent limit cycles at physically realizable parameters. We show that complexity in network topology is not necessary for complex behaviors to arise and that nonlinear rheology, in particular the plasma skimming effect, is sufficient to support oscillatory dynamics similar to those observed in vivo.

Materiomics: biological protein materials, from nano to macro

PubMed Central

Cranford, Steven; Buehler, Markus J

2010-01-01

Materiomics is an emerging field of science that provides a basis for multiscale material system characterization, inspired in part by natural, for example, protein-based materials. Here we outline the scope and explain the motivation of the field of materiomics, as well as demonstrate the benefits of a materiomic approach in the understanding of biological and natural materials as well as in the design of de novo materials. We discuss recent studies that exemplify the impact of materiomics – discovering Nature’s complexity through a materials science approach that merges concepts of material and structure throughout all scales and incorporates feedback loops that facilitate sensing and resulting structural changes at multiple scales. The development and application of materiomics is illustrated for the specific case of protein-based materials, which constitute the building blocks of a variety of biological systems such as tendon, bone, skin, spider silk, cells, and tissue, as well as natural composite material systems (a combination of protein-based and inorganic constituents) such as nacre and mollusk shells, and other natural multiscale systems such as cellulose-based plant and wood materials. An important trait of these materials is that they display distinctive hierarchical structures across multiple scales, where molecular details are exhibited in macroscale mechanical responses. Protein materials are intriguing examples of materials that balance multiple tasks, representing some of the most sustainable material solutions that integrate structure and function despite severe limitations in the quality and quantity of material building blocks. However, up until now, our attempts to analyze and replicate Nature’s materials have been hindered by our lack of fundamental understanding of these materials’ intricate hierarchical structures, scale-bridging mechanisms, and complex material components that bestow protein-based materials their unique properties. Recent advances in analytical tools and experimental methods allow a holistic view of such a hierarchical biological material system. The integration of these approaches and amalgamation of material properties at all scale levels to develop a complete description of a material system falls within the emerging field of materiomics. Materiomics is the result of the convergence of engineering and materials science with experimental and computational biology in the context of natural and synthetic materials. Through materiomics, fundamental advances in our understanding of structure–property–process relations of biological systems contribute to the mechanistic understanding of certain diseases and facilitate the development of novel biological, biologically inspired, and completely synthetic materials for applications in medicine (biomaterials), nanotechnology, and engineering. PMID:24198478

Beyond the Cell: Using Multiscalar Topics to Bring Interdisciplinarity into Undergraduate Cellular Biology Courses

PubMed Central

Weber, Carolyn F.

2016-01-01

Western science has grown increasingly reductionistic and, in parallel, the undergraduate life sciences curriculum has become disciplinarily fragmented. While reductionistic approaches have led to landmark discoveries, many of the most exciting scientific advances in the late 20th century have occurred at disciplinary interfaces; work at these interfaces is necessary to manage the world’s looming problems, particularly those that are rooted in cellular-level processes but have ecosystem- and even global-scale ramifications (e.g., nonsustainable agriculture, emerging infectious diseases). Managing such problems requires comprehending whole scenarios and their emergent properties as sums of their multiple facets and complex interrelationships, which usually integrate several disciplines across multiple scales (e.g., time, organization, space). This essay discusses bringing interdisciplinarity into undergraduate cellular biology courses through the use of multiscalar topics. Discussing how cellular-level processes impact large-scale phenomena makes them relevant to everyday life and unites diverse disciplines (e.g., sociology, cell biology, physics) as facets of a single system or problem, emphasizing their connections to core concepts in biology. I provide specific examples of multiscalar topics and discuss preliminary evidence that using such topics may increase students’ understanding of the cell’s position within an ecosystem and how cellular biology interfaces with other disciplines. PMID:27146162

How protein materials balance strength, robustness, and adaptability

PubMed Central

Buehler, Markus J.; Yung, Yu Ching

2010-01-01

Proteins form the basis of a wide range of biological materials such as hair, skin, bone, spider silk, or cells, which play an important role in providing key functions to biological systems. The focus of this article is to discuss how protein materials are capable of balancing multiple, seemingly incompatible properties such as strength, robustness, and adaptability. To illustrate this, we review bottom-up materiomics studies focused on the mechanical behavior of protein materials at multiple scales, from nano to macro. We focus on alpha-helix based intermediate filament proteins as a model system to explain why the utilization of hierarchical structural features is vital to their ability to combine strength, robustness, and adaptability. Experimental studies demonstrating the activation of angiogenesis, the growth of new blood vessels, are presented as an example of how adaptability of structure in biological tissue is achieved through changes in gene expression that result in an altered material structure. We analyze the concepts in light of the universality and diversity of the structural makeup of protein materials and discuss the findings in the context of potential fundamental evolutionary principles that control their nanoscale structure. We conclude with a discussion of multiscale science in biology and de novo materials design. PMID:20676305

Protein cage assembly across multiple length scales.

PubMed

Aumiller, William M; Uchida, Masaki; Douglas, Trevor

2018-05-21

Within the materials science community, proteins with cage-like architectures are being developed as versatile nanoscale platforms for use in protein nanotechnology. Much effort has been focused on the functionalization of protein cages with biological and non-biological moieties to bring about new properties of not only individual protein cages, but collective bulk-scale assemblies of protein cages. In this review, we report on the current understanding of protein cage assembly, both of the cages themselves from individual subunits, and the assembly of the individual protein cages into higher order structures. We start by discussing the key properties of natural protein cages (for example: size, shape and structure) followed by a review of some of the mechanisms of protein cage assembly and the factors that influence it. We then explore the current approaches for functionalizing protein cages, on the interior or exterior surfaces of the capsids. Lastly, we explore the emerging area of higher order assemblies created from individual protein cages and their potential for new and exciting collective properties.

Bioinspired Design: Magnetic Freeze Casting

NASA Astrophysics Data System (ADS)

Porter, Michael Martin

Nature is the ultimate experimental scientist, having billions of years of evolution to design, test, and adapt a variety of multifunctional systems for a plethora of diverse applications. Next-generation materials that draw inspiration from the structure-property-function relationships of natural biological materials have led to many high-performance structural materials with hybrid, hierarchical architectures that fit form to function. In this dissertation, a novel materials processing method, magnetic freeze casting, is introduced to develop porous scaffolds and hybrid composites with micro-architectures that emulate bone, abalone nacre, and other hard biological materials. This method uses ice as a template to form ceramic-based materials with continuously, interconnected microstructures and magnetic fields to control the alignment of these structures in multiple directions. The resulting materials have anisotropic properties with enhanced mechanical performance that have potential applications as bone implants or lightweight structural composites, among others.

Contact nanomechanical measurements with the AFM

NASA Astrophysics Data System (ADS)

Geisse, Nicholas

2013-03-01

The atomic force microscope (AFM) has found broad use in the biological sciences largely due to its ability to make measurements on unfixed and unstained samples under liquid. In addition to imaging at multiple spatial scales ranging from micro- to nanometer, AFMs are commonly used as nanomechanical probes. This is pertinent for cell biology, as it has been demonstrated that the geometrical and mechanical properties of the extracellular microenvironment are important in such processes as cancer, cardiovascular disease, muscular dystrophy, and even the control of cell life and death. Indeed, the ability to control and quantify these external geometrical and mechanical parameters arises as a key issue in the field. Because AFM can quantitatively measure the mechanical properties of various biological samples, novel insights to cell function and to cell-substrate interactions are now possible. As the application of AFM to these types of problems is widened, it is important to understand the performance envelope of the technique and its associated data analyses. This talk will discuss the important issues that must be considered when mechanical models are applied to real-world data. Examples of the effect of different model assumptions on our understanding of the measured material properties will be shown. Furthermore, specific examples of the importance of mechanical stimuli and the micromechanical environment to the structure and function of biological materials will be presented.

Self-Healing Gelatin Hydrogels Cross-Linked by Combining Multiple Hydrogen Bonding and Ionic Coordination.

PubMed

Zhang, Guangzhao; Lv, Lei; Deng, Yonghong; Wang, Chaoyang

2017-06-01

Self-healing hydrogels have been studied by many researchers via multiple cross-linking approaches including physical and chemical interactions. It is an interesting project in multifunctional hydrogel exploration that a water soluble polymer matrix is cross-linked by combining the ionic coordination and the multiple hydrogen bonds to fabricate self-healing hydrogels with injectable property. This study introduces a general procedure of preparing the hydrogels (termed gelatin-UPy-Fe) cross-linked by both ionic coordination of Fe 3+ and carboxyl group from the gelatin and the quadruple hydrogen bonding interaction from the ureido-pyrimidinone (UPy) dimers. The gelatin-UPy-Fe hydrogels possess an excellent self-healing property. The effects of the ionic coordination of Fe 3+ and quadruple hydrogen bonding of UPy on the formation and mechanical behavior of the prepared hydrogels are investigated. In vitro drug release of the gelatin-UPy-Fe hydrogels is also observed, giving an intriguing glimpse into possible biological applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The eyes have it: A Problem-Based Learning Exercise in Molecular Evolution.

PubMed

White, Harold B

2007-05-01

Molecular evolution provides an interesting context in which to use problem-based learning because it integrates a variety of topics in biology, biochemistry, and molecular biology. This three-stage problem for advanced students deals with the structure, multiple functions, and properties of lactate dehydrogenase isozymes, and the related evolutionary trade offs of gene sharing versus gene duplication among their corresponding genes. It has directive elements that require students to find and read classic articles, review thermodynamic principles, and apply their understanding to a mythical world wherein dinosaurs continued to evolve. The science fiction writing assignment that brings closure to the problem transformed the problem with respect to student interest and engagement. Copyright © 2007 International Union of Biochemistry and Molecular Biology, Inc.

Cooperativity in Monomeric Enzymes with Single Ligand-Binding Sites

PubMed Central

Porter, Carol M.

2011-01-01

Cooperativity is widespread in biology. It empowers a variety of regulatory mechanisms and impacts both the kinetic and thermodynamic properties of macromolecular systems. Traditionally, cooperativity is viewed as requiring the participation of multiple, spatially distinct binding sites that communicate via ligand-induced structural rearrangements; however, cooperativity requires neither multiple ligand binding events nor multimeric assemblies. An underappreciated manifestation of cooperativity has been observed in the non-Michaelis-Menten kinetic response of certain monomeric enzymes that possess only a single ligand-binding site. In this review, we present an overview of kinetic cooperativity in monomeric enzymes. We discuss the primary mechanisms postulated to give rise to monomeric cooperativity and highlight modern experimental methods that could offer new insights into the nature of this phenomenon. We conclude with an updated list of single subunit enzymes that are suspected of displaying cooperativity, and a discussion of the biological significance of this unique kinetic response. PMID:22137502

Computational prediction of protein hot spot residues.

PubMed

Morrow, John Kenneth; Zhang, Shuxing

2012-01-01

Most biological processes involve multiple proteins interacting with each other. It has been recently discovered that certain residues in these protein-protein interactions, which are called hot spots, contribute more significantly to binding affinity than others. Hot spot residues have unique and diverse energetic properties that make them challenging yet important targets in the modulation of protein-protein complexes. Design of therapeutic agents that interact with hot spot residues has proven to be a valid methodology in disrupting unwanted protein-protein interactions. Using biological methods to determine which residues are hot spots can be costly and time consuming. Recent advances in computational approaches to predict hot spots have incorporated a myriad of features, and have shown increasing predictive successes. Here we review the state of knowledge around protein-protein interactions, hot spots, and give an overview of multiple in silico prediction techniques of hot spot residues.

Computational Prediction of Hot Spot Residues

PubMed Central

Morrow, John Kenneth; Zhang, Shuxing

2013-01-01

Most biological processes involve multiple proteins interacting with each other. It has been recently discovered that certain residues in these protein-protein interactions, which are called hot spots, contribute more significantly to binding affinity than others. Hot spot residues have unique and diverse energetic properties that make them challenging yet important targets in the modulation of protein-protein complexes. Design of therapeutic agents that interact with hot spot residues has proven to be a valid methodology in disrupting unwanted protein-protein interactions. Using biological methods to determine which residues are hot spots can be costly and time consuming. Recent advances in computational approaches to predict hot spots have incorporated a myriad of features, and have shown increasing predictive successes. Here we review the state of knowledge around protein-protein interactions, hot spots, and give an overview of multiple in silico prediction techniques of hot spot residues. PMID:22316154

Fighting fire with fire: attacking the complexity of human tumors with armed therapeutic viruses.

PubMed

Hermiston, Terry

2002-08-01

Cancer gene therapies have centered on the use of a single gene, directed against a particular property or single aspect of tumor biology, to treat neoplastic disease. These therapies have met with limited clinical success. This is, perhaps, not surprising given the complex and heterogeneous nature of solid tumors. Treatments targeted at confronting multiple dimensions of human tumors are needed. Armed therapeutic viruses (oncolytic viruses carrying therapeutic genes) represent a system where the concerted action of multiple therapeutics can be joined into a single agent, and represent a promising avenue for developing future cancer therapies.

Analysis of a Viral Agent Isolated from Multiple Sclerosis Brain Tissue: Characterization as a Parainfluenzavirus Type 1

PubMed Central

Lewandowski, L. J.; Lief, F. S.; Verini, M. A.; Pienkowski, M. M.; ter Meulen, V.; Koprowski, H.

1974-01-01

A virus originally isolated from cell cultures obtained by lysolecithin-induced fusion of human multiple sclerosis brain cells with CV-1 cells has been analyzed for its antigenic, RNA, and polypeptide compositions, and for selective biological properties. Our findings establish that this isolate, designated 6/94 virus, contains a 50S RNA genome and is, as yet, indistinguishable from Sendai virus in its antigenic and total polypeptide compositions. Despite these similarities, the 6/94 and Sendai viruses differ in certain phenotypic properties. 6/94 virus is markedly less cytocidal for chick fibroblasts, especially at 37 C and, after β-propiolactone inactivation, it possesses a greater capacity for cell fusion and a lower toxicity than does comparably treated Sendai virus. In addition, 6/94 virus shows greater hemolytic activity. Images PMID:4363249

Machine learning aided diagnosis of hepatic malignancies through in vivo dielectric measurements with microwaves.

PubMed

Yilmaz, Tuba; Kılıç, Mahmut Alp; Erdoğan, Melike; Çayören, Mehmet; Tunaoğlu, Doruk; Kurtoğlu, İsmail; Yaslan, Yusuf; Çayören, Hüseyin; Arkan, Akif Enes; Teksöz, Serkan; Cancan, Gülden; Kepil, Nuray; Erdamar, Sibel; Özcan, Murat; Akduman, İbrahim; Kalkan, Tunaya

2016-06-20

In the past decade, extensive research on dielectric properties of biological tissues led to characterization of dielectric property discrepancy between the malignant and healthy tissues. Such discrepancy enabled the development of microwave therapeutic and diagnostic technologies. Traditionally, dielectric property measurements of biological tissues is performed with the well-known contact probe (open-ended coaxial probe) technique. However, the technique suffers from limited accuracy and low loss resolution for permittivity and conductivity measurements, respectively. Therefore, despite the inherent dielectric property discrepancy, a rigorous measurement routine with open-ended coaxial probes is required for accurate differentiation of malignant and healthy tissues. In this paper, we propose to eliminate the need for multiple measurements with open-ended coaxial probe for malignant and healthy tissue differentiation by applying support vector machine (SVM) classification algorithm to the dielectric measurement data. To do so, first, in vivo malignant and healthy rat liver tissue dielectric property measurements are collected with open-ended coaxial probe technique between 500 MHz to 6 GHz. Cole-Cole functions are fitted to the measured dielectric properties and measurement data is verified with the literature. Malign tissue classification is realized by applying SVM to the open-ended coaxial probe measurements where as high as 99.2% accuracy (F1 Score) is obtained.

Gingival Mesenchymal Stem/Progenitor Cells: A Unique Tissue Engineering Gem

PubMed Central

Fawzy El-Sayed, Karim M.; Dörfer, Christof E.

2016-01-01

The human gingiva, characterized by its outstanding scarless wound healing properties, is a unique tissue and a pivotal component of the periodontal apparatus, investing and surrounding the teeth in their sockets in the alveolar bone. In the last years gingival mesenchymal stem/progenitor cells (G-MSCs), with promising regenerative and immunomodulatory properties, have been isolated and characterized from the gingival lamina propria. These cells, in contrast to other mesenchymal stem/progenitor cell sources, are abundant, readily accessible, and easily obtainable via minimally invasive cell isolation techniques. The present review summarizes the current scientific evidence on G-MSCs' isolation, their characterization, the investigated subpopulations, the generated induced pluripotent stem cells- (iPSC-) like G-MSCs, their regenerative properties, and current approaches for G-MSCs' delivery. The review further demonstrates their immunomodulatory properties, the transplantation preconditioning attempts via multiple biomolecules to enhance their attributes, and the experimental therapeutic applications conducted to treat multiple diseases in experimental animal models in vivo. G-MSCs show remarkable tissue reparative/regenerative potential, noteworthy immunomodulatory properties, and primary experimental therapeutic applications of G-MSCs are very promising, pointing at future biologically based therapeutic techniques, being potentially superior to conventional clinical treatment modalities. PMID:27313628

Nonlinear signaling on biological networks: The role of stochasticity and spectral clustering

NASA Astrophysics Data System (ADS)

Hernandez-Hernandez, Gonzalo; Myers, Jesse; Alvarez-Lacalle, Enrique; Shiferaw, Yohannes

2017-03-01

Signal transduction within biological cells is governed by networks of interacting proteins. Communication between these proteins is mediated by signaling molecules which bind to receptors and induce stochastic transitions between different conformational states. Signaling is typically a cooperative process which requires the occurrence of multiple binding events so that reaction rates have a nonlinear dependence on the amount of signaling molecule. It is this nonlinearity that endows biological signaling networks with robust switchlike properties which are critical to their biological function. In this study we investigate how the properties of these signaling systems depend on the network architecture. Our main result is that these nonlinear networks exhibit bistability where the network activity can switch between states that correspond to a low and high activity level. We show that this bistable regime emerges at a critical coupling strength that is determined by the spectral structure of the network. In particular, the set of nodes that correspond to large components of the leading eigenvector of the adjacency matrix determines the onset of bistability. Above this transition the eigenvectors of the adjacency matrix determine a hierarchy of clusters, defined by its spectral properties, which are activated sequentially with increasing network activity. We argue further that the onset of bistability occurs either continuously or discontinuously depending upon whether the leading eigenvector is localized or delocalized. Finally, we show that at low network coupling stochastic transitions to the active branch are also driven by the set of nodes that contribute more strongly to the leading eigenvector. However, at high coupling, transitions are insensitive to network structure since the network can be activated by stochastic transitions of a few nodes. Thus this work identifies important features of biological signaling networks that may underlie their biological function.

Zonal Articular Cartilage Possesses Complex Mechanical Behavior Spanning Multiple Length Scales: Dependence on Chemical Heterogeneity, Anisotropy, and Microstructure

NASA Astrophysics Data System (ADS)

Wahlquist, Joseph A.

This work focused on characterizing the mechanical behavior of biological material in physiologically relevant conditions and at sub millimeter length scales. Elucidating the time, length scale, and directionally dependent mechanical behavior of cartilage and other biological materials is critical to adequately recapitulate native mechanosensory cues for cells, create computational models that mimic native tissue behavior, and assess disease progression. This work focused on three broad aspects of characterizing the mechanical behavior of articular cartilage. First, we sought to reveal the causes of time-dependent deformation and variation of mechanical properties with distance from the articular surface. Second, we investigated size dependence of mechanical properties. Finally, we examined material anisotropy of both the calcified and uncalcified tissues of the osteochondral interface. This research provides insight into how articular cartilage serves to support physiologic loads and simultaneously sustain chondrocyte viability.

Using Temporal Correlations and Full Distributions to Separate Intrinsic and Extrinsic Fluctuations in Biological Systems

NASA Astrophysics Data System (ADS)

Hilfinger, Andreas; Chen, Mark; Paulsson, Johan

2012-12-01

Studies of stochastic biological dynamics typically compare observed fluctuations to theoretically predicted variances, sometimes after separating the intrinsic randomness of the system from the enslaving influence of changing environments. But variances have been shown to discriminate surprisingly poorly between alternative mechanisms, while for other system properties no approaches exist that rigorously disentangle environmental influences from intrinsic effects. Here, we apply the theory of generalized random walks in random environments to derive exact rules for decomposing time series and higher statistics, rather than just variances. We show for which properties and for which classes of systems intrinsic fluctuations can be analyzed without accounting for extrinsic stochasticity and vice versa. We derive two independent experimental methods to measure the separate noise contributions and show how to use the additional information in temporal correlations to detect multiplicative effects in dynamical systems.

Physical and biological properties of U. S. standard endotoxin EC after exposure to ionizing radiation

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

Csako, G.; Elin, R.J.; Hochstein, H.D.

Techniques that reduce the toxicity of bacterial endotoxins are useful for studying the relationship between structure and biological activity. We used ionizing radiation to detoxify a highly refined endotoxin preparation. U.S. standard endotoxin EC. Dose-dependent changes occurred by exposure to /sup 60/Co-radiation in the physical properties and biological activities of the endotoxin. Sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis showed gradual loss of the polysaccharide components (O-side chain and R-core) from the endotoxin molecules. In contrast, although endotoxin revealed a complex absorption pattern in the UV range, radiation treatment failed to modify that pattern. Dose-related destruction of the primary toxic component,more » lipid A, was suggested by the results of activity tests: both the pyrogenicity and limulus reactivity of the endotoxin were destroyed by increasing doses of radiation. The results indicate that the detoxification is probably due to multiple effects of the ionizing radiation on bacterial lipopolysaccharides, and the action involves (i) the destruction of polysaccharide moieties and possibly (ii) the alteration of lipid A component of the endotoxin molecule.« less

Root Systems Biology: Integrative Modeling across Scales, from Gene Regulatory Networks to the Rhizosphere1

PubMed Central

Hill, Kristine; Porco, Silvana; Lobet, Guillaume; Zappala, Susan; Mooney, Sacha; Draye, Xavier; Bennett, Malcolm J.

2013-01-01

Genetic and genomic approaches in model organisms have advanced our understanding of root biology over the last decade. Recently, however, systems biology and modeling have emerged as important approaches, as our understanding of root regulatory pathways has become more complex and interpreting pathway outputs has become less intuitive. To relate root genotype to phenotype, we must move beyond the examination of interactions at the genetic network scale and employ multiscale modeling approaches to predict emergent properties at the tissue, organ, organism, and rhizosphere scales. Understanding the underlying biological mechanisms and the complex interplay between systems at these different scales requires an integrative approach. Here, we describe examples of such approaches and discuss the merits of developing models to span multiple scales, from network to population levels, and to address dynamic interactions between plants and their environment. PMID:24143806

Building a functional artery: issues from the perspective of mechanics.

PubMed

Gleason, Rudolph L; Hu, Jin-Jia; Humphrey, Jay D

2004-09-01

Despite the many successes of arterial tissue engineering, clinically viable implants may be a decade or more away. Fortunately, there is much more that we can learn from native vessels with regard to designing for optimal structure, function, and properties. Herein, we examine recent observations in vascular biology from the perspective of nonlinear mechanics. Moreover, we use a constrained mixture model to study potential contributions of individual wall constituents. In both cases, the unique biological and mechanical roles of elastin come to the forefront, especially its role in generating and modulating residual stress within the wall, which appears to be key to multiple growth and remodeling responses.

Faunal assemblages and multi-scale habitat patterns in headwater tributaries of the South Fork Trinity River - an unregulated river embedded within a multiple-use landscape

Treesearch

H. H. Jr. Welsh; J. J. G. R. Hodgson; J. M. Emlen Duda

2010-01-01

Headwaters can represent 80% of stream kilometers in a watershed, and they also have unique physical and biological properties that have only recently been recognized for their importance in sustaining healthy functioning stream networks and their ecological services. We sampled 60 headwater tributaries in the South Fork Trinity River, a 2,430 km2...

Characteristic Variations and Similarities in Biochemical, Molecular, and Functional Properties of Glyoxalases across Prokaryotes and Eukaryotes.

PubMed

Kaur, Charanpreet; Sharma, Shweta; Hasan, Mohammad Rokebul; Pareek, Ashwani; Singla-Pareek, Sneh L; Sopory, Sudhir K

2017-03-30

The glyoxalase system is the ubiquitous pathway for the detoxification of methylglyoxal (MG) in the biological systems. It comprises two enzymes, glyoxalase I (GLYI) and glyoxalase II (GLYII), which act sequentially to convert MG into d-lactate, thereby helping living systems get rid of this otherwise cytotoxic byproduct of metabolism. In addition, a glutathione-independent GLYIII enzyme activity also exists in the biological systems that can directly convert MG to d-lactate. Humans and Escherichia coli possess a single copy of GLYI (encoding either the Ni- or Zn-dependent form) and GLYII genes, which through MG detoxification provide protection against various pathological and disease conditions. By contrast, the plant genome possesses multiple GLYI and GLYII genes with a role in abiotic stress tolerance. Plants possess both Ni 2+ - and Zn 2+ -dependent forms of GLYI, and studies on plant glyoxalases reveal the various unique features of these enzymes distinguishing them from prokaryotic and other eukaryotic glyoxalases. Through this review, we provide an overview of the plant glyoxalase family along with a comparative analysis of glyoxalases across various species, highlighting similarities as well as differences in the biochemical, molecular, and physiological properties of these enzymes. We believe that the evolution of multiple glyoxalases isoforms in plants is an important component of their robust defense strategies.

Phosphatidic acid - a simple phospholipid with multiple faces.

PubMed

Zegarlińska, Jolanta; Piaścik, Magda; Sikorski, Aleksander F; Czogalla, Aleksander

2018-01-01

Phosphatidic acid (PA) is the simplest glycerophospholipid naturally occurring in living organisms, and even though its content among other cellular lipids is minor, it is drawing more and more attention due to its multiple biological functions. PA is a precursor for other phospholipids, acts as a lipid second messenger and, due to its structural properties, is also a modulator of membrane shape. Although much is known about interaction of PA with its effectors, the molecular mechanisms remain unresolved to a large degree. Throughout many of the well-characterized PA cellular sensors, no conserved binding domain can be recognized. Moreover, not much is known about the cellular dynamics of PA and how it is distributed among subcellular compartments. Remarkably, PA can play distinct roles within each of these compartments. For example, in the nucleus it behaves as a mitogen, influencing gene expression regulation, and in the Golgi membrane it plays a role in membrane trafficking. Here, we discuss how a biophysical experimental approach enabled PA behavior to be described in the context of a lipid bilayer and to what extent various physicochemical conditions may modulate the functional properties of this lipid. Understanding these aspects would help to unravel specific mechanisms of PA-driven membrane transformations and protein recruitment and thus would lead to a clearer picture of the biological role of PA.

Reconstruction of apparent orthotropic conductivity tensor image using magnetic resonance electrical impedance tomography

NASA Astrophysics Data System (ADS)

Sajib, Saurav Z. K.; Kim, Ji Eun; Jeong, Woo Chul; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je

2015-03-01

Magnetic resonance electrical impedance tomography visualizes current density and/or conductivity distributions inside an electrically conductive object. Injecting currents into the imaging object along at least two different directions, induced magnetic flux density data can be measured using a magnetic resonance imaging scanner. Without rotating the object inside the scanner, we can measure only one component of the magnetic flux density denoted as Bz. Since the biological tissues such as skeletal muscle and brain white matter show strong anisotropic properties, the reconstruction of anisotropic conductivity tensor is indispensable for the accurate observations in the biological systems. In this paper, we propose a direct method to reconstruct an axial apparent orthotropic conductivity tensor by using multiple Bz data subject to multiple injection currents. To investigate the anisotropic conductivity properties, we first recover the internal current density from the measured Bz data. From the recovered internal current density and the curl-free condition of the electric field, we derive an over-determined matrix system for determining the internal absolute orthotropic conductivity tensor. The over-determined matrix system is designed to use a combination of two loops around each pixel. Numerical simulations and phantom experimental results demonstrate that the proposed algorithm stably determines the orthotropic conductivity tensor.

Magnetic properties of checkerboard lattice: a Monte Carlo study

NASA Astrophysics Data System (ADS)

Jabar, A.; Masrour, R.; Hamedoun, M.; Benyoussef, A.

2017-12-01

The magnetic properties of ferrimagnetic mixed-spin Ising model in the checkerboard lattice are studied using Monte Carlo simulations. The variation of total magnetization and magnetic susceptibility with the crystal field has been established. We have obtained a transition from an order to a disordered phase in some critical value of the physical variables. The reduced transition temperature is obtained for different exchange interactions. The magnetic hysteresis cycles have been established. The multiples hysteresis cycle in checkerboard lattice are obtained. The multiples hysteresis cycle have been established. The ferrimagnetic mixed-spin Ising model in checkerboard lattice is very interesting from the experimental point of view. The mixed spins system have many technological applications such as in domain opto-electronics, memory, nanomedicine and nano-biological systems. The obtained results show that that crystal field induce long-range spin-spin correlations even bellow the reduced transition temperature.

Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides

NASA Astrophysics Data System (ADS)

Chen, Shiyu; Gopalakrishnan, Ranganath; Schaer, Tifany; Marger, Fabrice; Hovius, Ruud; Bertrand, Daniel; Pojer, Florence; Heinis, Christian

2014-11-01

The disulfide bonds that form between two cysteine residues are important in defining and rigidifying the structures of proteins and peptides. In polypeptides containing multiple cysteine residues, disulfide isomerization can lead to multiple products with different biological activities. Here, we describe the development of a dithiol amino acid (Dtaa) that can form two disulfide bridges at a single amino acid site. Application of Dtaas to a serine protease inhibitor and a nicotinic acetylcholine receptor inhibitor that contain disulfide constraints enhanced their inhibitory activities 40- and 7.6-fold, respectively. X-ray crystallographic and NMR structure analysis show that the peptide ligands containing Dtaas have retained their native tertiary structures. We furthermore show that replacement of two cysteines by Dtaas can avoid the formation of disulfide bond isomers. With these properties, Dtaas are likely to have broad application in the rational design or directed evolution of peptides and proteins with high activity and stability.

Protein location prediction using atomic composition and global features of the amino acid sequence

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

Cherian, Betsy Sheena, E-mail: betsy.skb@gmail.com; Nair, Achuthsankar S.

2010-01-22

Subcellular location of protein is constructive information in determining its function, screening for drug candidates, vaccine design, annotation of gene products and in selecting relevant proteins for further studies. Computational prediction of subcellular localization deals with predicting the location of a protein from its amino acid sequence. For a computational localization prediction method to be more accurate, it should exploit all possible relevant biological features that contribute to the subcellular localization. In this work, we extracted the biological features from the full length protein sequence to incorporate more biological information. A new biological feature, distribution of atomic composition is effectivelymore » used with, multiple physiochemical properties, amino acid composition, three part amino acid composition, and sequence similarity for predicting the subcellular location of the protein. Support Vector Machines are designed for four modules and prediction is made by a weighted voting system. Our system makes prediction with an accuracy of 100, 82.47, 88.81 for self-consistency test, jackknife test and independent data test respectively. Our results provide evidence that the prediction based on the biological features derived from the full length amino acid sequence gives better accuracy than those derived from N-terminal alone. Considering the features as a distribution within the entire sequence will bring out underlying property distribution to a greater detail to enhance the prediction accuracy.« less

Advances on plant-pathogen interactions from molecular toward systems biology perspectives.

PubMed

Peyraud, Rémi; Dubiella, Ullrich; Barbacci, Adelin; Genin, Stéphane; Raffaele, Sylvain; Roby, Dominique

2017-05-01

In the past 2 decades, progress in molecular analyses of the plant immune system has revealed key elements of a complex response network. Current paradigms depict the interaction of pathogen-secreted molecules with host target molecules leading to the activation of multiple plant response pathways. Further research will be required to fully understand how these responses are integrated in space and time, and exploit this knowledge in agriculture. In this review, we highlight systems biology as a promising approach to reveal properties of molecular plant-pathogen interactions and predict the outcome of such interactions. We first illustrate a few key concepts in plant immunity with a network and systems biology perspective. Next, we present some basic principles of systems biology and show how they allow integrating multiomics data and predict cell phenotypes. We identify challenges for systems biology of plant-pathogen interactions, including the reconstruction of multiscale mechanistic models and the connection of host and pathogen models. Finally, we outline studies on resistance durability through the robustness of immune system networks, the identification of trade-offs between immunity and growth and in silico plant-pathogen co-evolution as exciting perspectives in the field. We conclude that the development of sophisticated models of plant diseases incorporating plant, pathogen and climate properties represent a major challenge for agriculture in the future. © 2016 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

Galactic Cosmic Ray Event-Based Risk Model (GERM) Code

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Plante, Ianik; Ponomarev, Artem L.; Kim, Myung-Hee Y.

2013-01-01

This software describes the transport and energy deposition of the passage of galactic cosmic rays in astronaut tissues during space travel, or heavy ion beams in patients in cancer therapy. Space radiation risk is a probability distribution, and time-dependent biological events must be accounted for physical description of space radiation transport in tissues and cells. A stochastic model can calculate the probability density directly without unverified assumptions about shape of probability density function. The prior art of transport codes calculates the average flux and dose of particles behind spacecraft and tissue shielding. Because of the signaling times for activation and relaxation in the cell and tissue, transport code must describe temporal and microspatial density of functions to correlate DNA and oxidative damage with non-targeted effects of signals, bystander, etc. These are absolutely ignored or impossible in the prior art. The GERM code provides scientists data interpretation of experiments; modeling of beam line, shielding of target samples, and sample holders; and estimation of basic physical and biological outputs of their experiments. For mono-energetic ion beams, basic physical and biological properties are calculated for a selected ion type, such as kinetic energy, mass, charge number, absorbed dose, or fluence. Evaluated quantities are linear energy transfer (LET), range (R), absorption and fragmentation cross-sections, and the probability of nuclear interactions after 1 or 5 cm of water equivalent material. In addition, a set of biophysical properties is evaluated, such as the Poisson distribution for a specified cellular area, cell survival curves, and DNA damage yields per cell. Also, the GERM code calculates the radiation transport of the beam line for either a fixed number of user-specified depths or at multiple positions along the Bragg curve of the particle in a selected material. The GERM code makes the numerical estimates of basic physical and biophysical quantities of high-energy protons and heavy ions that have been studied at the NASA Space Radiation Laboratory (NSRL) for the purpose of simulating space radiation biological effects. In the first option, properties of monoenergetic beams are treated. In the second option, the transport of beams in different materials is treated. Similar biophysical properties as in the first option are evaluated for the primary ion and its secondary particles. Additional properties related to the nuclear fragmentation of the beam are evaluated. The GERM code is a computationally efficient Monte-Carlo heavy-ion-beam model. It includes accurate models of LET, range, residual energy, and straggling, and the quantum multiple scattering fragmentation (QMSGRG) nuclear database.

Thermal and optical characterization of biologically synthesized ZnS nanoparticles synthesized from an endophytic fungus Aspergillus flavus: A colorimetric probe in metal detection

NASA Astrophysics Data System (ADS)

Uddandarao, Priyanka; Balakrishnan, Raj Mohan

2017-03-01

Nanostructured semiconductor materials are of great importance for several technological applications due to their optical and thermal properties. The design and fabrication of metal sulfide nanoparticles with tunable properties for advanced applications have drawn a great deal of attention in the field of nanotechnology. ZnS is a potential II-IV group material which is used in hetero-junction solar cells, light emitting diodes, optoelectronic devices, electro luminescent devices and photovoltaic cells. Due to their multiple applications, there is a need to elucidate their thermal and optical properties. In the present study, thermal and optical properties of biologically synthesized ZnS nanoparticles are determined in detail with Thermal Gravimetric Analysis (TGA), Derivative Thermogravimetric Analysis (DTG), Differential Scanning Calorimeter (DSC), Diffuse Reflectance Spectroscopy (DRS), Photoluminescence (PL) and Raman spectroscopy. The results reveal that ZnS NPs exhibit a very strong quantum confinement with a significant increase in their optical band gap energy. These biologically synthesized ZnS NPs contain protein residues that can selectively bind with metal ions in aqueous solutions and can exhibit an aggregation-induced color change. This phenomenon is utilized to quantitatively measure the metal concentrations of Cu2 + and Mn2 + in this study. Further the stability of nanoparticles for the metal sensing process is accessed by UV-Vis spectrometer, zeta potential and cyclic voltammeter. The selectivity and sensitivity of ZnS NPs indicate its potential use as a sensor for metal detection in the ecosystem.

Passive lipoidal diffusion and carrier-mediated cell uptake are both important mechanisms of membrane permeation in drug disposition.

PubMed

Smith, Dennis; Artursson, Per; Avdeef, Alex; Di, Li; Ecker, Gerhard F; Faller, Bernard; Houston, J Brian; Kansy, Manfred; Kerns, Edward H; Krämer, Stefanie D; Lennernäs, Hans; van de Waterbeemd, Han; Sugano, Kiyohiko; Testa, Bernard

2014-06-02

Recently, it has been proposed that drug permeation is essentially carrier-mediated only and that passive lipoidal diffusion is negligible. This opposes the prevailing hypothesis of drug permeation through biological membranes, which integrates the contribution of multiple permeation mechanisms, including both carrier-mediated and passive lipoidal diffusion, depending on the compound's properties, membrane properties, and solution properties. The prevailing hypothesis of drug permeation continues to be successful for application and prediction in drug development. Proponents of the carrier-mediated only concept argue against passive lipoidal diffusion. However, the arguments are not supported by broad pharmaceutics literature. The carrier-mediated only concept lacks substantial supporting evidence and successful applications in drug development.

The Role of Reactive Oxygen Species (ROS) in the Biological Activities of Metallic Nanoparticles

PubMed Central

Abdal Dayem, Ahmed; Hossain, Mohammed Kawser; Lee, Soo Bin; Kim, Kyeongseok; Saha, Subbroto Kumar; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

2017-01-01

Nanoparticles (NPs) possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS). The amount of ROS produced by metallic NPs correlates with particle size, shape, surface area, and chemistry. ROS possess multiple functions in cellular biology, with ROS generation a key factor in metallic NP-induced toxicity, as well as modulation of cellular signaling involved in cell death, proliferation, and differentiation. In this review, we briefly explained NP classes and their biomedical applications and describe the sources and roles of ROS in NP-related biological functions in vitro and in vivo. Furthermore, we also described the roles of metal NP-induced ROS generation in stem cell biology. Although the roles of ROS in metallic NP-related biological functions requires further investigation, modulation and characterization of metallic NP-induced ROS production are promising in the application of metallic NPs in the areas of regenerative medicine and medical devices. PMID:28075405

8-Hydroxyquinolines: a review of their metal chelating properties and medicinal applications

PubMed Central

Prachayasittikul, Veda; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong

2013-01-01

Metal ions play an important role in biological processes and in metal homeostasis. Metal imbalance is the leading cause for many neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. 8-Hydroxyquinoline (8HQ) is a small planar molecule with a lipophilic effect and a metal chelating ability. As a result, 8HQ and its derivatives hold medicinal properties such as antineurodegenerative, anticancer, antioxidant, antimicrobial, anti-inflammatory, and antidiabetic activities. Herein, diverse bioactivities of 8HQ and newly synthesized 8HQ-based compounds are discussed together with their mechanisms of actions and structure–activity relationships. PMID:24115839

Quantum Feynman Ratchet

NASA Astrophysics Data System (ADS)

Goyal, Ketan; Kawai, Ryoichi

As nanotechnology advances, understanding of the thermodynamic properties of small systems becomes increasingly important. Such systems are found throughout physics, biology, and chemistry manifesting striking properties that are a direct result of their small dimensions where fluctuations become predominant. The standard theory of thermodynamics for macroscopic systems is powerless for such ever fluctuating systems. Furthermore, as small systems are inherently quantum mechanical, influence of quantum effects such as discreteness and quantum entanglement on their thermodynamic properties is of great interest. In particular, the quantum fluctuations due to quantum uncertainty principles may play a significant role. In this talk, we investigate thermodynamic properties of an autonomous quantum heat engine, resembling a quantum version of the Feynman Ratchet, in non-equilibrium condition based on the theory of open quantum systems. The heat engine consists of multiple subsystems individually contacted to different thermal environments.

Modular protein domains: an engineering approach toward functional biomaterials.

PubMed

Lin, Charng-Yu; Liu, Julie C

2016-08-01

Protein domains and peptide sequences are a powerful tool for conferring specific functions to engineered biomaterials. Protein sequences with a wide variety of functionalities, including structure, bioactivity, protein-protein interactions, and stimuli responsiveness, have been identified, and advances in molecular biology continue to pinpoint new sequences. Protein domains can be combined to make recombinant proteins with multiple functionalities. The high fidelity of the protein translation machinery results in exquisite control over the sequence of recombinant proteins and the resulting properties of protein-based materials. In this review, we discuss protein domains and peptide sequences in the context of functional protein-based materials, composite materials, and their biological applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multiplexed, quantitative, and targeted metabolite profiling by LC-MS/MRM.

PubMed

Wei, Ru; Li, Guodong; Seymour, Albert B

2014-01-01

Targeted metabolomics, which focuses on a subset of known metabolites representative of biologically relevant metabolic pathways, is a valuable tool to discover biomarkers and link disease phenotypes to underlying mechanisms or therapeutic modes of action. A key advantage of targeted metabolomics, compared to discovery metabolomics, is its immediate readiness for extracting biological information derived from known metabolites and quantitative measurements. However, simultaneously analyzing hundreds of endogenous metabolites presents a challenge due to their diverse chemical structures and properties. Here we report a method which combines different chromatographic separation conditions, optimal ionization polarities, and the most sensitive triple-quadrupole MS-based data acquisition mode, multiple reaction monitoring (MRM), to quantitatively profile 205 endogenous metabolites in 10 min.

Demystified … Nitric oxide

PubMed Central

Stuart-Smith, K

2002-01-01

The discovery of nitric oxide (NO) demonstrated that cells could communicate via the manufacture and local diffusion of an unstable lipid soluble molecule. Since the original demonstration of the vascular relaxant properties of endothelium derived NO, this fascinating molecule has been shown to have multiple, complex roles within many biological systems. This review cannot hope to cover all of the recent advances in NO biology, but seeks to place the discovery of NO in its historical context, and show how far our understanding has come in the past 20 years. The role of NO in mitochondrial respiration, and consequently in oxidative stress, is described in detail because these processes probably underline the importance of NO in the development of disease. PMID:12456772

Heterogeneous Deformable Modeling of Bio-Tissues and Haptic Force Rendering for Bio-Object Modeling

NASA Astrophysics Data System (ADS)

Lin, Shiyong; Lee, Yuan-Shin; Narayan, Roger J.

This paper presents a novel technique for modeling soft biological tissues as well as the development of an innovative interface for bio-manufacturing and medical applications. Heterogeneous deformable models may be used to represent the actual internal structures of deformable biological objects, which possess multiple components and nonuniform material properties. Both heterogeneous deformable object modeling and accurate haptic rendering can greatly enhance the realism and fidelity of virtual reality environments. In this paper, a tri-ray node snapping algorithm is proposed to generate a volumetric heterogeneous deformable model from a set of object interface surfaces between different materials. A constrained local static integration method is presented for simulating deformation and accurate force feedback based on the material properties of a heterogeneous structure. Biological soft tissue modeling is used as an example to demonstrate the proposed techniques. By integrating the heterogeneous deformable model into a virtual environment, users can both observe different materials inside a deformable object as well as interact with it by touching the deformable object using a haptic device. The presented techniques can be used for surgical simulation, bio-product design, bio-manufacturing, and medical applications.

Non-pathogenic microflora of a spring water with regenerative properties.

PubMed

Nicoletti, Giovanni; Corbella, Marta; Jaber, Omar; Marone, Piero; Scevola, Daniele; Faga, Angela

2015-11-01

The Comano spring water (Comano, Italy) has been demonstrated to improve skin regeneration, not only by increasing keratinocyte proliferation and migration, but also by modulating the regenerated collagen and elastic fibers in the dermis. However, such biological properties may not be entirely explained by its mineral composition only. As the non-pathogenic bacterial populations have demonstrated an active role in different biological processes, the potential presence of non-pathogenic bacterial species within the Comano spring water was investigated in order to identify any possible correlation between these bacterial populations and the demonstrated biological properties of this water. The water was collected at the spring using an aseptic procedure and multiple cultures were carried out. A total of 9 different strains were isolated, which were Aeromonas hydrophila , Brevundimonas vesicularis , Chromobacterium violaceum , Citrobacter youngae , Empedobacter brevis , Pantoea agglomerans , Pseudomonas putida , Pseudomonas stutzeri and Streptococcus mitis . All the isolated bacterial strains, although showing a rare potential virulence, demonstrated peculiar and favorable metabolic attitudes in controlling environmental pollution. The therapeutical effects of certain spring waters are currently being proven as correlated not only to their peculiar mineral composition, but also to the complex activity of their resident non-pathogenic bacterial populations. Although the present study provided only preliminary data, some of the non-pathogenic bacterial populations that were identified in the Comano spring water are likely to produce molecular mediators with a role in the wound healing process that, thus far, remain unknown. Numerous other unknown bacterial species, comprehensively termed DNA-rich 'dark matter', are likely to contribute to the Comano water regenerative properties as well. Therefore, the non-pathogenic bacterial populations of the Comano spring water are possibly credited for its demonstrated regenerative properties.

Voting systems for environmental decisions.

PubMed

Burgman, Mark A; Regan, Helen M; Maguire, Lynn A; Colyvan, Mark; Justus, James; Martin, Tara G; Rothley, Kris

2014-04-01

Voting systems aggregate preferences efficiently and are often used for deciding conservation priorities. Desirable characteristics of voting systems include transitivity, completeness, and Pareto optimality, among others. Voting systems that are common and potentially useful for environmental decision making include simple majority, approval, and preferential voting. Unfortunately, no voting system can guarantee an outcome, while also satisfying a range of very reasonable performance criteria. Furthermore, voting methods may be manipulated by decision makers and strategic voters if they have knowledge of the voting patterns and alliances of others in the voting populations. The difficult properties of voting systems arise in routine decision making when there are multiple criteria and management alternatives. Because each method has flaws, we do not endorse one method. Instead, we urge organizers to be transparent about the properties of proposed voting systems and to offer participants the opportunity to approve the voting system as part of the ground rules for operation of a group. © 2014 The Authors. Conservation Biology published by Wiley Periodicals, Inc., on behalf of the Society for Conservation Biology.

Beyond the therapeutic shackles of the monoamines: New mechanisms in bipolar disorder biology.

PubMed

Data-Franco, João; Singh, Ajeet; Popovic, Dina; Ashton, Melanie; Berk, Michael; Vieta, Eduard; Figueira, M L; Dean, Olivia M

2017-01-04

Multiple novel biological mechanisms putatively involved in the etiology of bipolar disorders are being explored. These include oxidative stress, altered glutamatergic neurotransmission, mitochondrial dysfunction, inflammation, cell signaling, apoptosis and impaired neurogenesis. Important clinical translational potential exists for such mechanisms to help underpin development of novel therapeutics - much needed given limitations of current therapies. These new mechanisms also help improve our understanding of how current therapeutics might exert their effects. Lithium, for example, appears to have antioxidant, immunomodulatory, signaling, anti-apoptotic and neuroprotective properties. Similar properties have been attributed to other mood stabilizers such as valproate, lamotrigine, and quetiapine. Perhaps of greatest translational value has been the recognition of such mechanisms leading to the emergence of novel therapeutics for bipolar disorders. These include the antioxidant N-acetylcysteine, the anti-inflammatory celecoxib, and ketamine - with effects on the glutamatergic system and microglial inhibition. We review these novel mechanisms and emerging therapeutics, and comment on next steps in this space. Copyright © 2016 Elsevier Inc. All rights reserved.

Magnetically multiplexed heating of single domain nanoparticles

NASA Astrophysics Data System (ADS)

Christiansen, M. G.; Senko, A. W.; Chen, R.; Romero, G.; Anikeeva, P.

2014-05-01

Selective hysteretic heating of multiple collocated types of single domain magnetic nanoparticles (SDMNPs) by alternating magnetic fields (AMFs) may offer a useful tool for biomedical applications. The possibility of "magnetothermal multiplexing" has not yet been realized, in part due to prevalent use of linear response theory to model SDMNP heating in AMFs. Dynamic hysteresis modeling suggests that specific driving conditions play an underappreciated role in determining optimal material selection strategies for high heat dissipation. Motivated by this observation, magnetothermal multiplexing is theoretically predicted and empirically demonstrated by selecting SDMNPs with properties that suggest optimal hysteretic heat dissipation at dissimilar AMF driving conditions. This form of multiplexing could effectively offer multiple channels for minimally invasive biological signaling applications.

Sequential Superresolution Imaging of Multiple Targets Using a Single Fluorophore

PubMed Central

Lidke, Diane S.; Lidke, Keith A.

2015-01-01

Fluorescence superresolution (SR) microscopy, or fluorescence nanoscopy, provides nanometer scale detail of cellular structures and allows for imaging of biological processes at the molecular level. Specific SR imaging methods, such as localization-based imaging, rely on stochastic transitions between on (fluorescent) and off (dark) states of fluorophores. Imaging multiple cellular structures using multi-color imaging is complicated and limited by the differing properties of various organic dyes including their fluorescent state duty cycle, photons per switching event, number of fluorescent cycles before irreversible photobleaching, and overall sensitivity to buffer conditions. In addition, multiple color imaging requires consideration of multiple optical paths or chromatic aberration that can lead to differential aberrations that are important at the nanometer scale. Here, we report a method for sequential labeling and imaging that allows for SR imaging of multiple targets using a single fluorophore with negligible cross-talk between images. Using brightfield image correlation to register and overlay multiple image acquisitions with ~10 nm overlay precision in the x-y imaging plane, we have exploited the optimal properties of AlexaFluor647 for dSTORM to image four distinct cellular proteins. We also visualize the changes in co-localization of the epidermal growth factor (EGF) receptor and clathrin upon EGF addition that are consistent with clathrin-mediated endocytosis. These results are the first to demonstrate sequential SR (s-SR) imaging using direct stochastic reconstruction microscopy (dSTORM), and this method for sequential imaging can be applied to any superresolution technique. PMID:25860558

Engineered Living Materials: Prospects and Challenges for Using Biological Systems to Direct the Assembly of Smart Materials.

PubMed

Nguyen, Peter Q; Courchesne, Noémie-Manuelle Dorval; Duraj-Thatte, Anna; Praveschotinunt, Pichet; Joshi, Neel S

2018-05-01

Vast potential exists for the development of novel, engineered platforms that manipulate biology for the production of programmed advanced materials. Such systems would possess the autonomous, adaptive, and self-healing characteristics of living organisms, but would be engineered with the goal of assembling bulk materials with designer physicochemical or mechanical properties, across multiple length scales. Early efforts toward such engineered living materials (ELMs) are reviewed here, with an emphasis on engineered bacterial systems, living composite materials which integrate inorganic components, successful examples of large-scale implementation, and production methods. In addition, a conceptual exploration of the fundamental criteria of ELM technology and its future challenges is presented. Cradled within the rich intersection of synthetic biology and self-assembling materials, the development of ELM technologies allows the power of biology to be leveraged to grow complex structures and objects using a palette of bio-nanomaterials. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

HPLC profiling of antimicrobial and antioxidant phyco sugars isolated from the South West coast of India.

PubMed

Kailas, Abhilash Parameswaran; Nair, Sukumaran Muraleedharan

2016-10-20

Phyco sugars isolated from the South West coast of India are commercially and therapeutically interesting due to their various biological activities. These sugars were isolated from six (three red and three green) seaweed species using water at 100°C followed by precipitation using ethanol. The physical, chemical and biological characteristics were explored with specific highlights onto the specific rotation, HPLC-RI sugar speciation, antioxidant and antimicrobial activities. The biological properties were evaluated based on multiple methods and standards, such that the actual nature of the sugar is understood. G. corticata var. cylindrica (31.66%) had the highest sugar content. All the sugars had levo rotatory specific rotation and interesting chemical characteristics. Sugars isolated had competitive biological activities and had the presence of seven monosaccharides and one disaccharide. The results highlighted the socio-economic importance of seaweeds which could be developed as a potential source of bioactive compounds in the upcoming future. Copyright © 2016 Elsevier Ltd. All rights reserved.

p-Coumaric acid and its conjugates: dietary sources, pharmacokinetic properties and biological activities.

PubMed

Pei, Kehan; Ou, Juanying; Huang, Junqing; Ou, Shiyi

2016-07-01

p-Coumaric acid (4-hydroxycinnamic acid) is a phenolic acid that has low toxicity in mice (LD50 = 2850 mg kg(-1) body weight), serves as a precursor of other phenolic compounds, and exists either in free or conjugated form in plants. Conjugates of p-coumaric acid have been extensively studied in recent years due to their bioactivities. In this review, the occurrence, bioavailability and bioaccessibility of p-coumaric acid and its conjugates with mono-, oligo- and polysaccharides, alkyl alcohols, organic acids, amine and lignin are discussed. Their biological activities, including antioxidant, anti-cancer, antimicrobial, antivirus, anti-inflammatory, antiplatelet aggregation, anxiolytic, antipyretic, analgesic, and anti-arthritis activities, and their mitigatory effects against diabetes, obesity, hyperlipaemia and gout are compared. Cumulative evidence from multiple studies indicates that conjugation of p-coumaric acid greatly strengthens its biological activities; however, the high biological activity but low absorption of its conjugates remains a puzzle. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Review of incursive, hyperincursive and anticipatory systems-foundation of anticipation in electromagnetism

NASA Astrophysics Data System (ADS)

Dubois, Daniel M.

2000-05-01

The main purpose of this paper is to show that anticipation is not only a property of biosystems but is also a fundamental property of physical systems. In electromagnetism, the anticipation is related to the Lorentz transform. In this framework the anticipation is a strong anticipation because it is not based on a prediction from a model of the physical system but is embedded in the fundamental system. So, Robert Rosen's anticipatory systems deal with weak anticipation. Contrary to Robert Rosen's affirmation, anticipation is thus not a characteristic of living systems. Finality is implicitly embedded in any system and thus the final cause of Aristotle is implicitly embedded in any physical and biological systems, contrary to what Robert Rosen argued. This paper will review some incursive and hyperincursive systems giving rise to strong anticipation. Space-time incursive parabolic systems show non-local properties. Hyperincursive crisp systems are related to catastrophe theory. Finally it will be shown that incursive and hyperincursive anticipatory systems could model properties of biosystems like free will, game strategy, theorem creation, etc. Anticipation is not only related to predictions but to decisions: hyperincursive systems create multiple choices and a decision process selects one choice. So, anticipation is not a final goal, like in cybernetics and system science, but is a fundamental property of physical and biological systems.

Characteristic Variations and Similarities in Biochemical, Molecular, and Functional Properties of Glyoxalases across Prokaryotes and Eukaryotes

PubMed Central

Kaur, Charanpreet; Sharma, Shweta; Hasan, Mohammad Rokebul; Pareek, Ashwani; Singla-Pareek, Sneh L.; Sopory, Sudhir K.

2017-01-01

The glyoxalase system is the ubiquitous pathway for the detoxification of methylglyoxal (MG) in the biological systems. It comprises two enzymes, glyoxalase I (GLYI) and glyoxalase II (GLYII), which act sequentially to convert MG into d-lactate, thereby helping living systems get rid of this otherwise cytotoxic byproduct of metabolism. In addition, a glutathione-independent GLYIII enzyme activity also exists in the biological systems that can directly convert MG to d-lactate. Humans and Escherichia coli possess a single copy of GLYI (encoding either the Ni- or Zn-dependent form) and GLYII genes, which through MG detoxification provide protection against various pathological and disease conditions. By contrast, the plant genome possesses multiple GLYI and GLYII genes with a role in abiotic stress tolerance. Plants possess both Ni2+- and Zn2+-dependent forms of GLYI, and studies on plant glyoxalases reveal the various unique features of these enzymes distinguishing them from prokaryotic and other eukaryotic glyoxalases. Through this review, we provide an overview of the plant glyoxalase family along with a comparative analysis of glyoxalases across various species, highlighting similarities as well as differences in the biochemical, molecular, and physiological properties of these enzymes. We believe that the evolution of multiple glyoxalases isoforms in plants is an important component of their robust defense strategies. PMID:28358304

Study of electromechanical and mechanical properties of bacteria using force microscopy

NASA Astrophysics Data System (ADS)

Reukov, Vladimir; Thompson, Gary; Nikiforov, Maxim; Guo, Senli; Ovchinnikov, Oleg; Jesse, Stephen; Kalinin, Sergei; Vertegel, Alexey

2010-03-01

The application of scanning probe microscopy (SPM) to biological systems has evolved over the past decade into a multimodal and spectroscopic instrument that provides multiple information channels at each spatial pixel acquired. Recently, functional recognition imaging based on differing electromechanical properties between Gram negative and Gram positive bacteria was achieved using artificial neural network analysis of band excitation piezoresponse force microscopy (BEPFM) data. The immediate goal of this project was to study mechanical and electromechanical properties of bacterial systems physiologically-relevant solutions using Band-width Excitation Piezoresponce Force Microscopy (BE PFM) in combination with Force Mapping. Electromechanical imaging in physiological environments will improve the versatility of functional recognition imaging and open the way for application of the rapid BEPFM line mode method to other living cell systems.

Bioengineered silk scaffolds in 3D tissue modeling with focus on mammary tissues.

PubMed

Maghdouri-White, Yas; Bowlin, Gary L; Lemmon, Christopher A; Dréau, Didier

2016-02-01

In vitro generation of three-dimensional (3D) biological tissues and organ-like structures is a promising strategy to study and closely model complex aspects of the molecular, cellular, and physiological interactions of tissue. In particular, in vitro 3D tissue modeling holds promises to further our understanding of breast development. Indeed, biologically relevant 3D structures that combine mammary cells and engineered matrices have improved our knowledge of mammary tissue growth, organization, and differentiation. Several polymeric biomaterials have been used as scaffolds to engineer 3D mammary tissues. Among those, silk fibroin-based biomaterials have many biologically relevant properties and have been successfully used in multiple medical applications. Here, we review the recent advances in engineered scaffolds with an emphasis on breast-like tissue generation and the benefits of modified silk-based scaffolds. Copyright © 2015 Elsevier B.V. All rights reserved.

Shadows of complexity: what biological networks reveal about epistasis and pleiotropy

PubMed Central

Tyler, Anna L.; Asselbergs, Folkert W.; Williams, Scott M.; Moore, Jason H.

2011-01-01

Pleiotropy, in which one mutation causes multiple phenotypes, has traditionally been seen as a deviation from the conventional observation in which one gene affects one phenotype. Epistasis, or gene-gene interaction, has also been treated as an exception to the Mendelian one gene-one phenotype paradigm. This simplified perspective belies the pervasive complexity of biology and hinders progress toward a deeper understanding of biological systems. We assert that epistasis and pleiotropy are not isolated occurrences, but ubiquitous and inherent properties of biomolecular networks. These phenomena should not be treated as exceptions, but rather as fundamental components of genetic analyses. A systems level understanding of epistasis and pleiotropy is, therefore, critical to furthering our understanding of human genetics and its contribution to common human disease. Finally, graph theory offers an intuitive and powerful set of tools with which to study the network bases of these important genetic phenomena. PMID:19204994

Biological properties of 6-gingerol: a brief review.

PubMed

Wang, Shaopeng; Zhang, Caihua; Yang, Guang; Yang, Yanzong

2014-07-01

Numerous studies have revealed that regular consumption of certain fruits and vegetables can reduce the risk of many diseases. The rhizome of Zingiber officinale (ginger) is consumed worldwide as a spice and herbal medicine. It contains pungent phenolic substances collectively known as gingerols. 6-Gingerol is the major pharmacologically-active component of ginger. It is known to exhibit a variety of biological activities including anticancer, anti-inflammation, and anti-oxidation. 6-Gingerol has been found to possess anticancer activities via its effect on a variety of biological pathways involved in apoptosis, cell cycle regulation, cytotoxic activity, and inhibition of angiogenesis. Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, 6-gingerol has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various diseases. Taken together, this review summarizes the various in vitro and in vivo pharmacological aspects of 6-gingerol and the underlying mechanisms.

The role of the NG2 proteoglycan in OPC and CNS network function.

PubMed

Sakry, Dominik; Trotter, Jacqueline

2016-05-01

In the normal mammalian CNS, the NG2 proteoglycan is expressed by oligodendrocyte precursor cells (OPC) but not by any other neural cell-type. NG2 is a type-1 membrane protein, exerting multiple roles in the CNS including intracellular signaling within the OPC, with effects on migration, cytoskeleton interaction and target gene regulation. It has been recently shown that the extracellular region of NG2, in addition to an adhesive function, acts as a soluble ECM component with the capacity to alter defined neuronal network properties. This region of NG2 is thus endowed with neuromodulatory properties. In order to generate biologically active fragments yielding these properties, the sequential cleavage of the NG2 protein by α- and γ-secretases occurs. The basal level of constitutive cleavage is stimulated by neuronal network activity. This processing leads to 4 major NG2 fragments which all have been associated with distinct biological functions. Here we summarize these functions, focusing on recent discoveries and their implications for the CNS. This article is part of a Special Issue entitled SI:NG2-glia(Invited only). Copyright © 2015 Elsevier B.V. All rights reserved.

A biologically based model for the integration of sensory-motor contingencies in rules and plans: a prefrontal cortex based extension of the Distributed Adaptive Control architecture.

PubMed

Duff, Armin; Fibla, Marti Sanchez; Verschure, Paul F M J

2011-06-30

Intelligence depends on the ability of the brain to acquire and apply rules and representations. At the neuronal level these properties have been shown to critically depend on the prefrontal cortex. Here we present, in the context of the Distributed Adaptive Control architecture (DAC), a biologically based model for flexible control and planning based on key physiological properties of the prefrontal cortex, i.e. reward modulated sustained activity and plasticity of lateral connectivity. We test the model in a series of pertinent tasks, including multiple T-mazes and the Tower of London that are standard experimental tasks to assess flexible control and planning. We show that the model is both able to acquire and express rules that capture the properties of the task and to quickly adapt to changes. Further, we demonstrate that this biomimetic self-contained cognitive architecture generalizes to planning. In addition, we analyze the extended DAC architecture, called DAC 6, as a model that can be applied for the creation of intelligent and psychologically believable synthetic agents. Copyright © 2010 Elsevier Inc. All rights reserved.

DAG tales: the multiple faces of diacylglycerol--stereochemistry, metabolism, and signaling.

PubMed

Eichmann, Thomas Oliver; Lass, Achim

2015-10-01

The neutral lipids diacylglycerols (DAGs) are involved in a plethora of metabolic pathways. They function as components of cellular membranes, as building blocks for glycero(phospho)lipids, and as lipid second messengers. Considering their central role in multiple metabolic processes and signaling pathways, cellular DAG levels require a tight regulation to ensure a constant and controlled availability. Interestingly, DAG species are versatile in their chemical structure. Besides the different fatty acid species esterified to the glycerol backbone, DAGs can occur in three different stereo/regioisoforms, each with unique biological properties. Recent scientific advances have revealed that DAG metabolizing enzymes generate and distinguish different DAG isoforms, and that only one DAG isoform holds signaling properties. Herein, we review the current knowledge of DAG stereochemistry and their impact on cellular metabolism and signaling. Further, we describe intracellular DAG turnover and its stereochemistry in a 3-pool model to illustrate the spatial and stereochemical separation and hereby the diversity of cellular DAG metabolism.

Oscillator networks with tissue-specific circadian clocks in plants.

PubMed

Inoue, Keisuke; Araki, Takashi; Endo, Motomu

2017-09-08

Many organisms rely on circadian clocks to synchronize their biological processes with the 24-h rotation of the earth. In mammals, the circadian clock consists of a central clock in the suprachiasmatic nucleus and peripheral clocks in other tissues. The central clock is tightly coupled to synchronize rhythmicity and can organize peripheral clocks through neural and hormonal signals. In contrast to mammals, it has long been assumed that the circadian clocks in each plant cell is able to be entrained by external light, and they are only weakly coupled to each other. Recently, however, several reports have demonstrated that plants have unique oscillator networks with tissue-specific circadian clocks. Here, we introduce our current view regarding tissue-specific properties and oscillator networks of plant circadian clocks. Accumulating evidence suggests that plants have multiple oscillators, which show distinct properties and reside in different tissues. A direct tissue-isolation technique and micrografting have clearly demonstrated that plants have hierarchical oscillator networks consisting of multiple tissue-specific clocks. Copyright © 2017. Published by Elsevier Ltd.

Local Geometry and Evolutionary Conservation of Protein Surfaces Reveal the Multiple Recognition Patches in Protein-Protein Interactions

PubMed Central

Laine, Elodie; Carbone, Alessandra

2015-01-01

Protein-protein interactions (PPIs) are essential to all biological processes and they represent increasingly important therapeutic targets. Here, we present a new method for accurately predicting protein-protein interfaces, understanding their properties, origins and binding to multiple partners. Contrary to machine learning approaches, our method combines in a rational and very straightforward way three sequence- and structure-based descriptors of protein residues: evolutionary conservation, physico-chemical properties and local geometry. The implemented strategy yields very precise predictions for a wide range of protein-protein interfaces and discriminates them from small-molecule binding sites. Beyond its predictive power, the approach permits to dissect interaction surfaces and unravel their complexity. We show how the analysis of the predicted patches can foster new strategies for PPIs modulation and interaction surface redesign. The approach is implemented in JET2, an automated tool based on the Joint Evolutionary Trees (JET) method for sequence-based protein interface prediction. JET2 is freely available at www.lcqb.upmc.fr/JET2. PMID:26690684

Accurate RNA 5-methylcytosine site prediction based on heuristic physical-chemical properties reduction and classifier ensemble.

PubMed

Zhang, Ming; Xu, Yan; Li, Lei; Liu, Zi; Yang, Xibei; Yu, Dong-Jun

2018-06-01

RNA 5-methylcytosine (m 5 C) is an important post-transcriptional modification that plays an indispensable role in biological processes. The accurate identification of m 5 C sites from primary RNA sequences is especially useful for deeply understanding the mechanisms and functions of m 5 C. Due to the difficulty and expensive costs of identifying m 5 C sites with wet-lab techniques, developing fast and accurate machine-learning-based prediction methods is urgently needed. In this study, we proposed a new m 5 C site predictor, called M5C-HPCR, by introducing a novel heuristic nucleotide physicochemical property reduction (HPCR) algorithm and classifier ensemble. HPCR extracts multiple reducts of physical-chemical properties for encoding discriminative features, while the classifier ensemble is applied to integrate multiple base predictors, each of which is trained based on a separate reduct of the physical-chemical properties obtained from HPCR. Rigorous jackknife tests on two benchmark datasets demonstrate that M5C-HPCR outperforms state-of-the-art m 5 C site predictors, with the highest values of MCC (0.859) and AUC (0.962). We also implemented the webserver of M5C-HPCR, which is freely available at http://cslab.just.edu.cn:8080/M5C-HPCR/. Copyright © 2018 Elsevier Inc. All rights reserved.

Mathematical and numerical challenges in living biological materials

NASA Astrophysics Data System (ADS)

Forest, M. Gregory; Vasquez, Paula A.

2013-10-01

The proclaimed Century of Biology is rapidly leading to the realization of how starkly different and more complex biological materials are than the materials that underpinned the industrial and technological revolution. These differences arise, in part, because biological matter exhibits both viscous and elastic behavior. Moreover, this behavior varies across the frequency, wavelength and amplitude spectrum of forcing. This broadclass of responsesin biological matter requires multiple frequency-dependent functions to specify material behavior, instead of a discrete set of parameters that relate to either viscosity or elasticity. This complexity prevails even if the biological matter is assumed to be spatially homogeneous, which is rarely true. However, very little progress has been made on the characterization of heterogeneity and how to build that information into constitutive laws and predictive models. In addition, most biological matter is non-stationary, which motivates the term "living". Biomaterials typically are in an active state in order to perform certain functions, and they often are modified or replenished on the basis of external stimuli. It has become popular in materials engineering to try to duplicate some of the functionality of biomaterials, e.g., a lot of effort has gone into the design of self-assembling, self-healing and shape shifting materials. These distinguishing features of biomaterials require significantly more degrees of freedom than traditional composites and many of the molecular species and their roles in functionality have yet to be determined. A typical biological material includes small molecule biochemical species that react and diffuse within larger species. These large molecular weightspecies provide the primary structural and biophysical properties of the material. The small molecule binding and unbinding kinetics serves to modulate material properties, and typical small molecule production and release are governed by external stimuli (e.g., stress). The bottom line is that the mathematical and numerical tools of 20th Century materials science are often insufficient for describing biological materials and for predicting their behavior both in vitro and in vivo.

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

Yusufoglu, Yusuf

Nature offers many exciting ideas and inspiration for the development of new materials and processes. The toughness of spider silk, the strength and lightweight of bone, and the adhesion abilities of the gecko's feet are some of the many examples of highperformance natural materials, which have attracted the interest of scientist to duplicate their properties in man-made materials. Materials found in nature combine many inspiring properties such as miniaturization, sophistication, hierarchical organization, hybridization, and adaptability. In all biological systems, whether very basic or highly complex, nature provides a multiplicity of materials, architectures, systems and functions. Generally, the architectural configurations andmore » material characteristics are the important features that have been duplicated from nature for building synthetic structural composites.« less

Hypoxia and the extracellular matrix: drivers of tumour metastasis

PubMed Central

Gilkes, Daniele M.; Semenza, Gregg L.; Wirtz, Denis

2014-01-01

Of the deaths attributed to cancer, 90% are due to metastasis, and treatments that prevent or cure metastasis remain elusive. Emerging data indicate that hypoxia and the extracellular matrix (ECM) might have crucial roles in metastasis. During tumour evolution, changes in the composition and the overall content of the ECM reflect both its biophysical and biological properties and these strongly influence tumour and stromal cell properties, such as proliferation and motility. Originally thought of as independent contributors to metastatic spread, recent studies have established a direct link between hypoxia and the composition and the organization of the ECM, which suggests a new model in which multiple microenvironmental signals might converge to synergistically influence metastatic outcome. PMID:24827502

Dissection of Biological Property of Chinese Acupuncture Point Zusanli Based on Long-Term Treatment via Modulating Multiple Metabolic Pathways.

PubMed

Yan, Guangli; Zhang, Aihua; Sun, Hui; Cheng, Weiping; Meng, Xiangcai; Liu, Li; Zhang, Yingzhi; Xie, Ning; Wang, Xijun

2013-01-01

Acupuncture has a history of over 3000 years and is a traditional Chinese medical therapy that uses hair-thin metal needles to puncture the skin at specific points on the body to promote wellbeing, while its molecular mechanism and ideal biological pathways are still not clear. High-throughput metabolomics is the global assessment of endogenous metabolites within a biologic system and can potentially provide a more accurate snap shot of the actual physiological state. We hypothesize that acupuncture-treated human would produce unique characterization of metabolic phenotypes. In this study, UPLC/ESI-HDMS coupled with pattern recognition methods and system analysis were carried out to investigate the mechanism and metabolite biomarkers for acupuncture treatment at "Zusanli" acupoint (ST-36) as a case study. The top 5 canonical pathways including alpha-linolenic acid metabolism, d-glutamine and d-glutamate metabolism, citrate cycle, alanine, aspartate, and glutamate metabolism, and vitamin B6 metabolism pathways were acutely perturbed, and 53 differential metabolites were identified by chemical profiling and may be useful to clarify the physiological basis and mechanism of ST-36. More importantly, network construction has led to the integration of metabolites associated with the multiple perturbation pathways. Urine metabolic profiling might be a promising method to investigate the molecular mechanism of acupuncture.

Development of hydrogels for regenerative engineering.

PubMed

Guan, Xiaofei; Avci-Adali, Meltem; Alarçin, Emine; Cheng, Hao; Kashaf, Sara Saheb; Li, Yuxiao; Chawla, Aditya; Jang, Hae Lin; Khademhosseini, Ali

2017-05-01

The aim of regenerative engineering is to restore complex tissues and biological systems through convergence in the fields of advanced biomaterials, stem cell science, and developmental biology. Hydrogels are one of the most attractive biomaterials for regenerative engineering, since they can be engineered into tissue mimetic 3D scaffolds to support cell growth due to their similarity to native extracellular matrix. Advanced nano- and micro-technologies have dramatically increased the ability to control properties and functionalities of hydrogel materials by facilitating biomimetic fabrication of more sophisticated compositions and architectures, thus extending our understanding of cell-matrix interactions at the nanoscale. With this perspective, this review discusses the most commonly used hydrogel materials and their fabrication strategies for regenerative engineering. We highlight the physical, chemical, and functional modulation of hydrogels to design and engineer biomimetic tissues based on recent achievements in nano- and micro-technologies. In addition, current hydrogel-based regenerative engineering strategies for treating multiple tissues, such as musculoskeletal, nervous and cardiac tissue, are also covered in this review. The interaction of multiple disciplines including materials science, cell biology, and chemistry, will further play an important role in the design of functional hydrogels for the regeneration of complex tissues. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Cancer Systems Biology Consortium | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

Cancer is a complex disease system involving multiple molecular, genetic, and cellular events. From its early initiation through progression and metastasis, cancer can adapt and evolve as a result of both internal and external signals. These properties make cancer difficult to predict, prevent, and treat. There has been significant progress in characterizing the genetics of cancer, as well as the downstream effects on the molecular and cellular pathways that are critical for the initiation and progression of cancer.

Evolutionary distances in the twilight zone--a rational kernel approach.

PubMed

Schwarz, Roland F; Fletcher, William; Förster, Frank; Merget, Benjamin; Wolf, Matthias; Schultz, Jörg; Markowetz, Florian

2010-12-31

Phylogenetic tree reconstruction is traditionally based on multiple sequence alignments (MSAs) and heavily depends on the validity of this information bottleneck. With increasing sequence divergence, the quality of MSAs decays quickly. Alignment-free methods, on the other hand, are based on abstract string comparisons and avoid potential alignment problems. However, in general they are not biologically motivated and ignore our knowledge about the evolution of sequences. Thus, it is still a major open question how to define an evolutionary distance metric between divergent sequences that makes use of indel information and known substitution models without the need for a multiple alignment. Here we propose a new evolutionary distance metric to close this gap. It uses finite-state transducers to create a biologically motivated similarity score which models substitutions and indels, and does not depend on a multiple sequence alignment. The sequence similarity score is defined in analogy to pairwise alignments and additionally has the positive semi-definite property. We describe its derivation and show in simulation studies and real-world examples that it is more accurate in reconstructing phylogenies than competing methods. The result is a new and accurate way of determining evolutionary distances in and beyond the twilight zone of sequence alignments that is suitable for large datasets.

Synergistic Synthetic Biology: Units in Concert

PubMed Central

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications. PMID:25022769

Synergistic Synthetic Biology: Units in Concert.

PubMed

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

Designing allostery-inspired response in mechanical networks

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

Rocks, Jason W.; Pashine, Nidhi; Bischofberger, Irmgard

Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are then able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ~1% of the bonds. We are also able to control multiple pairs of target nodes, each with a different individualmore » response, from a single source, and to tune multiple independent source/target responses simultaneously into a network. We have fabricated physical networks in macroscopic 2D and 3D systems that exhibit these responses. This work is inspired by the long-range coupled conformational changes that constitute allosteric function in proteins. The fact that allostery is a common means for regulation in biological molecules suggests that it is a relatively easy property to develop through evolution. In analogy, our results show that long-range coupled mechanical responses are similarly easy to achieve in disordered networks.« less

Linking optical properties of dissolved organic matter to multiple processes at the coastal plume zone in the East China Sea.

PubMed

Jiang, Yulin; Zhao, Jianfu; Li, Penghui; Huang, Qinghui

2016-10-12

Because of the significance in photosynthesis, nutrient dynamics, trophodynamics and biological activity, dissolved organic matter (DOM) is important to the microbial community in the coastal plume zone. In this study, we investigated the hydrodynamic processes, photodegradation and biodegradation of DOM at the Yangtze River plume in the East China Sea through analyzing water quality and optical properties of DOM. Surface water samples were collected to examine water quality and fluorescence properties of fluorescent dissolved organic matter (FDOM). The results indicated that dilution was the key factor in the multiple processes, and the mixing process gradually increased from nearshore to offshore in coastal water. Four components of FDOM representing humic-like substances (C1 & C4) and protein-like substances (C2 & C3) were identified, and all components showed nearly conservative behaviors. Protein-like substances were more mutable compared to humic-like substances. The photodegradation of humic-like substances caused brown algae blooms to some extent. The molecular weight of humic substances gradually decreased along the mixing process. FDOM in the plume zone was both of terrigenous and autochthonous origins, and the characteristic of terrigenous origin was obvious compared to that of autochthonous origin.

Designing allostery-inspired response in mechanical networks

DOE PAGES

Rocks, Jason W.; Pashine, Nidhi; Bischofberger, Irmgard; ...

2017-02-21

Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are then able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ~1% of the bonds. We are also able to control multiple pairs of target nodes, each with a different individualmore » response, from a single source, and to tune multiple independent source/target responses simultaneously into a network. We have fabricated physical networks in macroscopic 2D and 3D systems that exhibit these responses. This work is inspired by the long-range coupled conformational changes that constitute allosteric function in proteins. The fact that allostery is a common means for regulation in biological molecules suggests that it is a relatively easy property to develop through evolution. In analogy, our results show that long-range coupled mechanical responses are similarly easy to achieve in disordered networks.« less

Designing allostery-inspired response in mechanical networks

PubMed Central

Rocks, Jason W.; Pashine, Nidhi; Bischofberger, Irmgard; Goodrich, Carl P.; Liu, Andrea J.; Nagel, Sidney R.

2017-01-01

Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ∼1% of the bonds. We are also able to control multiple pairs of target nodes, each with a different individual response, from a single source, and to tune multiple independent source/target responses simultaneously into a network. We have fabricated physical networks in macroscopic 2D and 3D systems that exhibit these responses. This work is inspired by the long-range coupled conformational changes that constitute allosteric function in proteins. The fact that allostery is a common means for regulation in biological molecules suggests that it is a relatively easy property to develop through evolution. In analogy, our results show that long-range coupled mechanical responses are similarly easy to achieve in disordered networks. PMID:28223534

Designing allostery-inspired response in mechanical networks.

PubMed

Rocks, Jason W; Pashine, Nidhi; Bischofberger, Irmgard; Goodrich, Carl P; Liu, Andrea J; Nagel, Sidney R

2017-03-07

Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ∼1% of the bonds. We are also able to control multiple pairs of target nodes, each with a different individual response, from a single source, and to tune multiple independent source/target responses simultaneously into a network. We have fabricated physical networks in macroscopic 2D and 3D systems that exhibit these responses. This work is inspired by the long-range coupled conformational changes that constitute allosteric function in proteins. The fact that allostery is a common means for regulation in biological molecules suggests that it is a relatively easy property to develop through evolution. In analogy, our results show that long-range coupled mechanical responses are similarly easy to achieve in disordered networks.

Concanavalin-A conjugated fine-multiple emulsion loaded with 6-mercaptopurine.

PubMed

Khopade, A J; Jain, N K

2000-01-01

Fine-multiple (water-in-oil-in-water) emulsions were prepared by two-step emulsification using sonication. They were coated with concanavalin-A (Con-A) by three methods. The one involving covalent coupling of Con-A to the multiple emulsion incorporated anchor was better compared with lipid derivatized Con-A anchoring or the glutaraldehyde-based cross-linking method, as shown by the faster rate of dextran-induced aggregation. The selected multiple emulsions were characterized by physical properties such as droplet size, encapsulation efficiency, and zeta potential. Stability parameters such as droplet size, creaming, leakage, and aggregation as a function of relative turbidity were monitored over a 1-month period, which revealed good stability of the formulations. The release profile of 6-mercaptopurine followed zero-order kinetics. Pharmacokinetic studies showed an increase in half-life and bioavailability from multiple emulsion formulations administered intravenously. There was prolonged retention of drug in various tissues of rats when treated with Con-A-coated multiple emulsion as compared with uncoated one. Our study demonstrates the suitability of fine-multiple emulsion for intravenous administration and the potential for prolonged retention of drugs and targeting in biological systems.

Subsurface Hydrology: Data Integration for Properties and Processes

NASA Astrophysics Data System (ADS)

Hyndman, David W.; Day-Lewis, Frederick D.; Singha, Kamini

Groundwater is a critical resource and the PrinciPal source of drinking water for over 1.5 billion people. In 2001, the National Research Council cited as a "grand challenge" our need to understand the processes that control water movement in the subsurface. This volume faces that challenge in terms of data integration between complex, multi-scale hydrologie processes, and their links to other physical, chemical, and biological processes at multiple scales. Subsurface Hydrology: Data Integration for Properties and Processes presents the current state of the science in four aspects: • Approaches to hydrologie data integration • Data integration for characterization of hydrologie properties • Data integration for understanding hydrologie processes • Meta-analysis of current interpretations Scientists and researchers in the field, the laboratory, and the classroom will find this work an important resource in advancing our understanding of subsurface water movement.

Multiscale Feature Analysis of Salivary Gland Branching Morphogenesis

PubMed Central

Baydil, Banu; Daley, William P.; Larsen, Melinda; Yener, Bülent

2012-01-01

Pattern formation in developing tissues involves dynamic spatio-temporal changes in cellular organization and subsequent evolution of functional adult structures. Branching morphogenesis is a developmental mechanism by which patterns are generated in many developing organs, which is controlled by underlying molecular pathways. Understanding the relationship between molecular signaling, cellular behavior and resulting morphological change requires quantification and categorization of the cellular behavior. In this study, tissue-level and cellular changes in developing salivary gland in response to disruption of ROCK-mediated signaling by are modeled by building cell-graphs to compute mathematical features capturing structural properties at multiple scales. These features were used to generate multiscale cell-graph signatures of untreated and ROCK signaling disrupted salivary gland organ explants. From confocal images of mouse submandibular salivary gland organ explants in which epithelial and mesenchymal nuclei were marked, a multiscale feature set capturing global structural properties, local structural properties, spectral, and morphological properties of the tissues was derived. Six feature selection algorithms and multiway modeling of the data was performed to identify distinct subsets of cell graph features that can uniquely classify and differentiate between different cell populations. Multiscale cell-graph analysis was most effective in classification of the tissue state. Cellular and tissue organization, as defined by a multiscale subset of cell-graph features, are both quantitatively distinct in epithelial and mesenchymal cell types both in the presence and absence of ROCK inhibitors. Whereas tensor analysis demonstrate that epithelial tissue was affected the most by inhibition of ROCK signaling, significant multiscale changes in mesenchymal tissue organization were identified with this analysis that were not identified in previous biological studies. We here show how to define and calculate a multiscale feature set as an effective computational approach to identify and quantify changes at multiple biological scales and to distinguish between different states in developing tissues. PMID:22403724

Open Innovation Drug Discovery (OIDD): a potential path to novel therapeutic chemical space.

PubMed

Alvim-Gaston, Maria; Grese, Timothy; Mahoui, Abdelaziz; Palkowitz, Alan D; Pineiro-Nunez, Marta; Watson, Ian

2014-01-01

The continued development of computational and synthetic methods has enabled the enumeration or preparation of a nearly endless universe of chemical structures. Nevertheless, the ability of this chemical universe to deliver small molecules that can both modulate biological targets and have drug-like physicochemical properties continues to be a topic of interest to the pharmaceutical industry and academic researchers alike. The chemical space described by public, commercial, in-house and virtual compound collections has been interrogated by multiple approaches including biochemical, cellular and virtual screening, diversity analysis, and in-silico profiling. However, current drugs and known chemical probes derived from these efforts are contained within a remarkably small volume of the predicted chemical space. Access to more diverse classes of chemical scaffolds that maintain the properties relevant for drug discovery is certainly needed to meet the increasing demands for pharmaceutical innovation. The Lilly Open Innovation Drug Discovery platform (OIDD) was designed to tackle barriers to innovation through the identification of novel molecules active in relevant disease biology models. In this article we will discuss several computational approaches towards describing novel, biologically active, drug-like chemical space and illustrate how the OIDD program may facilitate access to previously untapped molecules that may aid in the search for innovative pharmaceuticals.

Chemokines beyond chemo-attraction: CXCL10 and its significant role in cancer and autoimmunity.

PubMed

Karin, Nathan; Razon, Hila

2018-09-01

Chemokines are mostly known for their chemotactic properties, and less for their ability to direct the biological function of target cells, including T cells. The current review focuses on a key chemokine named CXCL10 and its role in directing the migratory propertied and biological function of CD4+ and CD8+ T cells in the context of cancer and inflammatory autoimmunity. CXCR3 is a chemokine receptor that is abundant on CD4+ T cells, CD8+ T cells and NK cells. It has three known ligands: CXCL9, CXCL10 and CXCL11. Different studies, including those coming form our laboratory, indicated that aside of attracting CD8+ and CD4+ effector T cells to tumor sites and sites of inflammation CXCL10 directs the polarization and potentiates the biological function of these cells. This makes CXCL10 a "key driver chemokine" and a valid target for therapy of autoimmune diseases such as Inflammatory Bowl's Disease, Multiple Sclerosis, Rheumatoid arthritis and others. As for cancer this motivated different groups, including our group to develop CXCL10 based therapies for cancer due to its ability to enhance T-dependent anti cancer immunity. The current review summarizes these findings and their potential translational implication. Copyright © 2018 Elsevier Ltd. All rights reserved.

Father Involvement and Young, Rural African American Men's Engagement in Substance Misuse and Multiple Sexual Partnerships.

PubMed

Barton, Allen W; Kogan, Steven M; Cho, Junhan; Brown, Geoffrey L

2015-12-01

This study was designed to examine the associations of biological father and social father involvement during childhood with African American young men's development and engagement in risk behaviors. With a sample of 505 young men living in the rural South of the United States, a dual mediation model was tested in which retrospective reports of involvement from biological fathers and social fathers were linked to young men's substance misuse and multiple sexual partnerships through men's relational schemas and future expectations. Results from structural equation modeling indicated that levels of involvement from biological fathers and social fathers predicted young men's relational schemas; only biological fathers' involvement predicted future expectations. In turn, future expectations predicted levels of substance misuse, and negative relational schemas predicted multiple sexual partnerships. Biological fathers' involvement evinced significant indirect associations with young men's substance misuse and multiple sexual partnerships through both schemas and expectations; social fathers' involvement exhibited an indirect association with multiple sexual partnerships through relational schemas. Findings highlight the unique influences of biological fathers and social fathers on multiple domains of African American young men's psychosocial development that subsequently render young men more or less likely to engage in risk behaviors.

The isolation and characterisation of jacalin [Artocarpus heterophyllus (jackfruit) lectin] based on its charge properties.

PubMed

Kabir, S

1995-02-01

Jackfruit extracts contain a protein termed jacalin which possesses diverse biological properties. A detailed analysis of its charge properties has been lacking. The present investigation was initiated to study isoelectric properties of jacalin in detail and to isolate a single isoform of jacalin. Jacalin was isolated from jackfruit extracts by affinity chromatography on immunoglobulin-A immobilised to Sepharose 4B. Various techniques such as ion-exchange chromatography, isoelectric focusing (IEF) on polyacrylamide gels and preparative liquid IEF with the Rotofor cell were used. When analysed by IEF on thin layer polyacrylamide gels, jacalin was resolved into 35 bands over a pH range of 5.0-8.5. Upon SDS-PAGE in the second dimension all these charge species gave rise to only two-bands at 12 and 15.4 kDa. The lectin was mostly eluted with 50 and 100 mM sodium chloride when jackfruit extracts were fractionated on an anion-exchange column of DEAE-cellulose. In a single 6 hour run by preparative IEF with the Rotofor cell in the pH range of 3-9.5, it has been possible to isolate pure jacalin fractions containing fewer number of charged isomers. A single jacalin isoform was isolated by subjecting a Rotofor fraction containing fewer charged species to preparative IEF on thin layer polyacrylamide gel and eluting the band of interest from the gel. The isolated jacalin isoform was biologically active as it agglutinated erythrocytes. The study reveals the complexity of jacalin as it exists as multiple charge isomers over a broad pH range. By performing preparative IEF in solution as well as in thin layer polyacrylamide gels, it was possible to isolate a single jacalin isoform with the retention of biological activity.

A survey of enabling technologies in synthetic biology

PubMed Central

2013-01-01

Background Realizing constructive applications of synthetic biology requires continued development of enabling technologies as well as policies and practices to ensure these technologies remain accessible for research. Broadly defined, enabling technologies for synthetic biology include any reagent or method that, alone or in combination with associated technologies, provides the means to generate any new research tool or application. Because applications of synthetic biology likely will embody multiple patented inventions, it will be important to create structures for managing intellectual property rights that best promote continued innovation. Monitoring the enabling technologies of synthetic biology will facilitate the systematic investigation of property rights coupled to these technologies and help shape policies and practices that impact the use, regulation, patenting, and licensing of these technologies. Results We conducted a survey among a self-identifying community of practitioners engaged in synthetic biology research to obtain their opinions and experiences with technologies that support the engineering of biological systems. Technologies widely used and considered enabling by survey participants included public and private registries of biological parts, standard methods for physical assembly of DNA constructs, genomic databases, software tools for search, alignment, analysis, and editing of DNA sequences, and commercial services for DNA synthesis and sequencing. Standards and methods supporting measurement, functional composition, and data exchange were less widely used though still considered enabling by a subset of survey participants. Conclusions The set of enabling technologies compiled from this survey provide insight into the many and varied technologies that support innovation in synthetic biology. Many of these technologies are widely accessible for use, either by virtue of being in the public domain or through legal tools such as non-exclusive licensing. Access to some patent protected technologies is less clear and use of these technologies may be subject to restrictions imposed by material transfer agreements or other contract terms. We expect the technologies considered enabling for synthetic biology to change as the field advances. By monitoring the enabling technologies of synthetic biology and addressing the policies and practices that impact their development and use, our hope is that the field will be better able to realize its full potential. PMID:23663447

Exploring the Hybridization Thermodynamics of Spherical Nucleic Acids to Tailor Probes for Diagnostic and Therapeutic Applications

NASA Astrophysics Data System (ADS)

Randeria, Pratik Shailesh

Spherical nucleic acids (SNAs), three-dimensional nanoparticle conjugates composed of densely packed and highly oriented oligonucleotides around organic or inorganic nanoparticles, are an emergent class of nanostructures that show promise as single-entity agents for intracellular messenger RNA (mRNA) detection and gene regulation. SNAs exhibit superior biocompatibility and biological properties compared to linear oligonucleotides, enabling them to overcome many of the limitations of linear oligonucleotides for use in biomedical applications. However, the origins of these biologically attractive properties are not well understood. In this dissertation, the chemistry underlying one such property is studied in detail, and the findings are applied towards the rational design of more effective SNAs for diagnostic and therapeutic applications. Chapter 1 introduces the synthesis of SNAs, the unique properties that make them superior to linear nucleic acids for biomedicine, and previously studied applications of these structures. Chapter 2 focuses on quantitatively studying the impact of the chemical structure of the SNA on its ability to hybridize multiple complementary nucleic acids. This chapter lays the groundwork for understanding the factors that govern SNA hybridization thermodynamics and how to tailor SNAs to increase their binding affinity to target mRNA strands. Chapters 3 and 4 capitalize on this knowledge to engineer probes for intracellular mRNA detection and gene regulation applications. Chapter 3 reports the development of an SNA-based probe that can simultaneously report the expression level of two different mRNA transcripts in live cells and differentiate diseased cells from non-diseased cells. Chapter 4 investigates the use of topically-applied SNAs to down-regulate a critical mediator of impaired wound healing in diabetic mice to accelerate wound closure. This study represents the first topical therapeutic application of SNA nanotechnology to treat open wounds and lays the groundwork for developing SNA-based approaches for treating any skin-related disorder with a known genetic signature. Chapter 5 summarizes the key findings and conclusions and introduces future research directions. Taken together, this work demonstrates the important, and often surprising, role nanostructure plays in controlling biological properties and supports the continued development of SNAs as probes for molecular and medical biology.

The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part I: cellular response.

PubMed

Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

2015-02-01

Osteoarthritis (OA) is a complex disease of the joint for which current treatments are unsatisfactory, thus motivating development of tissue engineering (TE)-based therapies. To date, TE strategies have had some success, developing replacement tissue constructs with biochemical properties approaching that of native cartilage. However, poor biomechanical properties and limited postimplantation integration with surrounding tissue are major shortcomings that need to be addressed. Functional tissue engineering strategies that apply physiologically relevant biophysical cues provide a platform to improve TE constructs before implantation. In the previous decade, new experimental and theoretical findings in cartilage biomechanics and electromechanics have emerged, resulting in an increased understanding of the complex interplay of multiple biophysical cues in the extracellular matrix of the tissue. The effect of biophysical stimulation on cartilage, and the resulting chondrocyte-mediated biosynthesis, remodeling, degradation, and repair, has, therefore, been extensively explored by the TE community. This article compares and contrasts the cellular response of chondrocytes to multiple biophysical stimuli, and may be read in conjunction with its companion paper that compares and contrasts the subsequent intracellular signal transduction cascades. Mechanical, magnetic, and electrical stimuli promote proliferation, differentiation, and maturation of chondrocytes within established dose parameters or "biological windows." This knowledge will provide a framework for ongoing studies incorporating multiple biophysical cues in TE functional neocartilage for treatment of OA.

A novel method of predicting microRNA-disease associations based on microRNA, disease, gene and environment factor networks.

PubMed

Peng, Wei; Lan, Wei; Zhong, Jiancheng; Wang, Jianxin; Pan, Yi

2017-07-15

MicroRNAs have been reported to have close relationship with diseases due to their deregulation of the expression of target mRNAs. Detecting disease-related microRNAs is helpful for disease therapies. With the development of high throughput experimental techniques, a large number of microRNAs have been sequenced. However, it is still a big challenge to identify which microRNAs are related to diseases. Recently, researchers are interesting in combining multiple-biological information to identify the associations between microRNAs and diseases. In this work, we have proposed a novel method to predict the microRNA-disease associations based on four biological properties. They are microRNA, disease, gene and environment factor. Compared with previous methods, our method makes predictions not only by using the prior knowledge of associations among microRNAs, disease, environment factors and genes, but also by using the internal relationship among these biological properties. We constructed four biological networks based on the similarity of microRNAs, diseases, environment factors and genes, respectively. Then random walking was implemented on the four networks unequally. In the walking course, the associations can be inferred from the neighbors in the same networks. Meanwhile the association information can be transferred from one network to another. The results of experiment showed that our method achieved better prediction performance than other existing state-of-the-art methods. Copyright © 2017 Elsevier Inc. All rights reserved.

Moringa Genus: A Review of Phytochemistry and Pharmacology

PubMed Central

Abd Rani, Nur Zahirah; Husain, Khairana; Kumolosasi, Endang

2018-01-01

Moringa is a genus of medicinal plants that has been used traditionally to cure wounds and various diseases such as colds and diabetes. In addition, the genus is also consumed as a source of nutrients and widely used for purifying water. The genus consists of 13 species that have been widely cultivated throughout Asia and Africa for their multiple uses. The purpose of this review is to provide updated and categorized information on the traditional uses, phytochemistry, biological activities, and toxicological research of Moringa species in order to explore their therapeutic potential and evaluate future research opportunities. The literature reviewed for this paper was obtained from PubMed, ScienceDirect, and Google Scholar journal papers published from 1983 to March 2017. Moringa species are well-known for their antioxidant, anti-inflammatory, anticancer, and antihyperglycemic activities. Most of their biological activity is caused by their high content of flavonoids, glucosides, and glucosinolates. By documenting the traditional uses and biological activities of Moringa species, we hope to support new research on these plants, especially on those species whose biological properties have not been studied to date. PMID:29503616

Integrated experimental platforms to study blast injuries: a bottom-up approach

NASA Astrophysics Data System (ADS)

Bo, C.; Williams, A.; Rankin, S.; Proud, W. G.; Brown, K. A.

2014-05-01

We are developing experimental models of blast injury using data from live biological samples. An integrated research strategy is followed to study material and biological properties of cells, tissues and organs, that are subjected to dynamic and static pressures, relevant to those of battlefield blast. We have developed a confined Split Hopkinson Pressure Bar (SHPB) system, which allows cells, either in suspension or as a monolayer, to be subjected to compression waves with pressures on the order of a few MPa and durations of hundreds of microseconds. The chamber design enables recovery of biological samples for cellular and molecular analysis. The SHPB platform, coupled with Quasi-Static experiments, is used to determine stress-strain curves of soft biological tissues under compression at low, medium and high strain rates. Tissue samples are examined, using histological techniques, to study macro- and microscopic changes induced by compression waves. In addition, a shock tube enables application of single or multiple air blasts with pressures on the order of kPa and a few milliseconds duration; this platform was used for initial studies on mesenchymal stem cells responses to blast pressures.

Chalcone: A Privileged Structure in Medicinal Chemistry.

PubMed

Zhuang, Chunlin; Zhang, Wen; Sheng, Chunquan; Zhang, Wannian; Xing, Chengguo; Miao, Zhenyuan

2017-06-28

Privileged structures have been widely used as an effective template in medicinal chemistry for drug discovery. Chalcone is a common simple scaffold found in many naturally occurring compounds. Many chalcone derivatives have also been prepared due to their convenient synthesis. These natural products and synthetic compounds have shown numerous interesting biological activities with clinical potentials against various diseases. This review aims to highlight the recent evidence of chalcone as a privileged scaffold in medicinal chemistry. Multiple aspects of chalcone will be summarized herein, including the isolation of novel chalcone derivatives, the development of new synthetic methodologies, the evaluation of their biological properties, and the exploration of the mechanisms of action as well as target identification. This review is expected to be a comprehensive, authoritative, and critical review of the chalcone template to the chemistry community.

Photodynamic therapy in prostate cancer: optical dosimetry and response of normal tissue

NASA Astrophysics Data System (ADS)

Chen, Qun; Shetty, Sugandh D.; Heads, Larry; Bolin, Frank; Wilson, Brian C.; Patterson, Michael S.; Sirls, Larry T., II; Schultz, Daniel; Cerny, Joseph C.; Hetzel, Fred W.

1993-06-01

The present study explores the possibility of utilizing photodynamic therapy (PDT) in treating localized prostate carcinoma. Optical properties of ex vivo human prostatectomy specimens, and in vivo and ex vivo dog prostate glands were studied. The size of the PDT induced lesion in dog prostate was pathologically evaluated as a biological endpoint. The data indicate that the human normal and carcinoma prostate tissues have similar optical properties. The average effective attenuation depth is less in vivo than that of ex vivo. The PDT treatment generated a lesion size of up to 16 mm in diameter. The data suggest that PDT is a promising modality in prostate cancer treatment. Multiple fiber system may be required for clinical treatment.

[Therapeutic potential of Cannabis sativa].

PubMed

Avello L, Marcia; Pastene N, Edgar; Fernández R, Pola; Córdova M, Pia

2017-03-01

Cannabis sativa (marihuana) is considered an illicit drug due to its psychoactive properties. Recently, the Chilean government opened to the use cannabis in the symptomatic treatment of some patients. The biological effects of cannabis render it useful for the complementary treatment of specific clinical situations such as chronic pain. We retrieved scientific information about the analgesic properties of cannabis, using it as a safe drug. The drug may block or inhibit the transmission of nervous impulses at different levels, an effect associated with pain control. Within this context and using adequate doses, forms and administration pathways, it can be used for chronic pain management, considering its effectiveness and low cost. It could also be considered as an alternative in patients receiving prolonged analgesic therapies with multiple adverse effects.

BIOLOGICAL AND BIOPHYSICAL PROPERTIES OF VASCULAR CONNEXIN CHANNELS

PubMed Central

Johnstone, Scott; Isakson, Brant; Locke, Darren

2010-01-01

Intercellular channels formed by connexin proteins play a pivotal role in the direct movement of ions and larger cytoplasmic solutes between vascular endothelial cells, between vascular smooth muscle cells, and between endothelial and smooth muscle cells. Multiple genetic and epigenetic factors modulate connexin expression levels and/or channel function, including cell type-independent and cell type-specific transcription factors, posttranslational modification and localized membrane targeting. Additionally, differences in protein-protein interactions, including those between connexins, significantly contribute to both vascular homeostasis and disease progression. The biophysical properties of the connexin channels identified in the vasculature, those formed by Cx37, Cx40, Cx43 and/or Cx45 proteins, are discussed in this review in the physiological and pathophysiological context of vessel function. PMID:19815177

Order Matters: The Order of Somatic Mutations Influences Cancer Evolution.

PubMed

Kent, David G; Green, Anthony R

2017-04-03

Cancers evolve as a consequence of multiple somatic lesions, with competition between subclones and sequential subclonal evolution. Some driver mutations arise either early or late in the evolution of different individual tumors, suggesting that the final malignant properties of a subclone reflect the sum of mutations acquired rather than the order in which they arose. However, very little is known about the cellular consequences of altering the order in which mutations are acquired. Recent studies of human myeloproliferative neoplasms show that the order in which individual mutations are acquired has a dramatic impact on the cell biological and molecular properties of tumor-initiating cells. Differences in clinical presentation, complications, and response to targeted therapy were all observed and implicate mutation order as an important player in cancer biology. These observations represent the first demonstration that the order of mutation acquisition influences stem and progenitor cell behavior and clonal evolution in any cancer. Thus far, the impact of different mutation orders has only been studied in hematological malignancies, and analogous studies of solid cancers are now required. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Error-based analysis of optimal tuning functions explains phenomena observed in sensory neurons.

PubMed

Yaeli, Steve; Meir, Ron

2010-01-01

Biological systems display impressive capabilities in effectively responding to environmental signals in real time. There is increasing evidence that organisms may indeed be employing near optimal Bayesian calculations in their decision-making. An intriguing question relates to the properties of optimal encoding methods, namely determining the properties of neural populations in sensory layers that optimize performance, subject to physiological constraints. Within an ecological theory of neural encoding/decoding, we show that optimal Bayesian performance requires neural adaptation which reflects environmental changes. Specifically, we predict that neuronal tuning functions possess an optimal width, which increases with prior uncertainty and environmental noise, and decreases with the decoding time window. Furthermore, even for static stimuli, we demonstrate that dynamic sensory tuning functions, acting at relatively short time scales, lead to improved performance. Interestingly, the narrowing of tuning functions as a function of time was recently observed in several biological systems. Such results set the stage for a functional theory which may explain the high reliability of sensory systems, and the utility of neuronal adaptation occurring at multiple time scales.

Genetically encoded lipid-polypeptide hybrid biomaterials that exhibit temperature-triggered hierarchical self-assembly

NASA Astrophysics Data System (ADS)

Mozhdehi, Davoud; Luginbuhl, Kelli M.; Simon, Joseph R.; Dzuricky, Michael; Berger, Rüdiger; Varol, H. Samet; Huang, Fred C.; Buehne, Kristen L.; Mayne, Nicholas R.; Weitzhandler, Isaac; Bonn, Mischa; Parekh, Sapun H.; Chilkoti, Ashutosh

2018-05-01

Post-translational modification of proteins is a strategy widely used in biological systems. It expands the diversity of the proteome and allows for tailoring of both the function and localization of proteins within cells as well as the material properties of structural proteins and matrices. Despite their ubiquity in biology, with a few exceptions, the potential of post-translational modifications in biomaterials synthesis has remained largely untapped. As a proof of concept to demonstrate the feasibility of creating a genetically encoded biohybrid material through post-translational modification, we report here the generation of a family of three stimulus-responsive hybrid materials—fatty-acid-modified elastin-like polypeptides—using a one-pot recombinant expression and post-translational lipidation methodology. These hybrid biomaterials contain an amphiphilic domain, composed of a β-sheet-forming peptide that is post-translationally functionalized with a C14 alkyl chain, fused to a thermally responsive elastin-like polypeptide. They exhibit temperature-triggered hierarchical self-assembly across multiple length scales with varied structure and material properties that can be controlled at the sequence level.

Functionally-interdependent shape-switching nanoparticles with controllable properties

PubMed Central

Halman, Justin R.; Satterwhite, Emily; Roark, Brandon; Chandler, Morgan; Viard, Mathias; Ivanina, Anna; Bindewald, Eckart; Kasprzak, Wojciech K.; Panigaj, Martin; Bui, My N.; Lu, Jacob S.; Miller, Johann; Khisamutdinov, Emil F.; Shapiro, Bruce A.; Dobrovolskaia, Marina A.

2017-01-01

Abstract We introduce a new concept that utilizes cognate nucleic acid nanoparticles which are fully complementary and functionally-interdependent to each other. In the described approach, the physical interaction between sets of designed nanoparticles initiates a rapid isothermal shape change which triggers the activation of multiple functionalities and biological pathways including transcription, energy transfer, functional aptamers and RNA interference. The individual nanoparticles are not active and have controllable kinetics of re-association and fine-tunable chemical and thermodynamic stabilities. Computational algorithms were developed to accurately predict melting temperatures of nanoparticles of various compositions and trace the process of their re-association in silico. Additionally, tunable immunostimulatory properties of described nanoparticles suggest that the particles that do not induce pro-inflammatory cytokines and high levels of interferons can be used as scaffolds to carry therapeutic oligonucleotides, while particles with strong interferon and mild pro-inflammatory cytokine induction may qualify as vaccine adjuvants. The presented concept provides a simple, cost-effective and straightforward model for the development of combinatorial regulation of biological processes in nucleic acid nanotechnology. PMID:28108656

Developmental Origins of Biological Explanations: The case of infants' internal property bias.

PubMed

Taborda-Osorio, Hernando; Cheries, Erik W

2017-10-01

People's explanations about the biological world are heavily biased toward internal, non-obvious properties. Adults and children as young as 5 years of age find internal properties more causally central than external features for explaining general biological processes and category membership. In this paper, we describe how this 'internal property bias' may be grounded in two different developmental precursors observed in studies with infants: (1) an early understanding of biological agency that is apparent in infants' reasoning about animals, and (2) the acquisition of kind-based representations that distinguish between essential and accidental properties, spanning from animals to artifacts. We argue that these precursors may support the progressive construction of the notion of biological kinds and explanations during childhood. Shortly after their first year of life, infants seem to represent the internal properties of animates as more central and identity-determining that external properties. Over time, this skeletal notion of biological kinds is integrated into diverse explanations about kind membership and biological processes, with an increasingly better understanding of the causal role of internal properties.

Engineering of vault nanocapsules with enzymatic and fluorescent properties

PubMed Central

Kickhoefer, Valerie A.; Garcia, Yvette; Mikyas, Yeshi; Johansson, Erik; Zhou, Jing C.; Raval-Fernandes, Sujna; Minoofar, Payam; Zink, Jeffrey I.; Dunn, Bruce; Stewart, Phoebe L.; Rome, Leonard H.

2005-01-01

One of the central issues facing the emerging field of nanotechnology is cellular compatibility. Nanoparticles have been proposed for diagnostic and therapeutic applications, including drug delivery, gene therapy, biological sensors, and controlled catalysis. Viruses, liposomes, peptides, and synthetic and natural polymers have been engineered for these applications, yet significant limitations continue to prevent their use. Avoidance of the body's natural immune system, lack of targeting specificity, and the inability to control packaging and release are remaining obstacles. We have explored the use of a naturally occurring cellular nanoparticle known as the vault, which is named for its morphology with multiple arches reminiscent of cathedral ceilings. Vaults are 13-MDa ribonucleoprotein particles with an internal cavity large enough to sequester hundreds of proteins. Here, we report a strategy to target and sequester biologically active materials within the vault cavity. Attachment of a vault-targeting peptide to two proteins, luciferase and a variant of GFP, resulted in their sequestration within the vault cavity. The targeted proteins confer enzymatic and fluorescent properties on the recombinant vaults, both of which can be detected by their emission of light. The modified vaults are compatible with living cells. The ability to engineer vault particles with designed properties and functionalities represents an important step toward development of a biocompatible nanocapsule. PMID:15753293

Engineering of vault nanocapsules with enzymatic and fluorescent properties.

PubMed

Kickhoefer, Valerie A; Garcia, Yvette; Mikyas, Yeshi; Johansson, Erik; Zhou, Jing C; Raval-Fernandes, Sujna; Minoofar, Payam; Zink, Jeffrey I; Dunn, Bruce; Stewart, Phoebe L; Rome, Leonard H

2005-03-22

One of the central issues facing the emerging field of nanotechnology is cellular compatibility. Nanoparticles have been proposed for diagnostic and therapeutic applications, including drug delivery, gene therapy, biological sensors, and controlled catalysis. Viruses, liposomes, peptides, and synthetic and natural polymers have been engineered for these applications, yet significant limitations continue to prevent their use. Avoidance of the body's natural immune system, lack of targeting specificity, and the inability to control packaging and release are remaining obstacles. We have explored the use of a naturally occurring cellular nanoparticle known as the vault, which is named for its morphology with multiple arches reminiscent of cathedral ceilings. Vaults are 13-MDa ribonucleoprotein particles with an internal cavity large enough to sequester hundreds of proteins. Here, we report a strategy to target and sequester biologically active materials within the vault cavity. Attachment of a vault-targeting peptide to two proteins, luciferase and a variant of GFP, resulted in their sequestration within the vault cavity. The targeted proteins confer enzymatic and fluorescent properties on the recombinant vaults, both of which can be detected by their emission of light. The modified vaults are compatible with living cells. The ability to engineer vault particles with designed properties and functionalities represents an important step toward development of a biocompatible nanocapsule.

Sub–100-nm metafluorophores with digitally tunable optical properties self-assembled from DNA

PubMed Central

Woehrstein, Johannes B.; Strauss, Maximilian T.; Ong, Luvena L.; Wei, Bryan; Zhang, David Y.; Jungmann, Ralf; Yin, Peng

2017-01-01

Fluorescence microscopy allows specific target detection down to the level of single molecules and has become an enabling tool in biological research. To transduce the biological information to an imageable signal, we have developed a variety of fluorescent probes, such as organic dyes or fluorescent proteins with different colors. Despite their success, a limitation on constructing small fluorescent probes is the lack of a general framework to achieve precise and programmable control of critical optical properties, such as color and brightness. To address this challenge, we introduce metafluorophores, which are constructed as DNA nanostructure–based fluorescent probes with digitally tunable optical properties. Each metafluorophore is composed of multiple organic fluorophores, organized in a spatially controlled fashion in a compact sub–100-nm architecture using a DNA nanostructure scaffold. Using DNA origami with a size of 90 × 60 nm2, substantially smaller than the optical diffraction limit, we constructed small fluorescent probes with digitally tunable brightness, color, and photostability and demonstrated a palette of 124 virtual colors. Using these probes as fluorescent barcodes, we implemented an assay for multiplexed quantification of nucleic acids. Additionally, we demonstrated the triggered in situ self-assembly of fluorescent DNA nanostructures with prescribed brightness upon initial hybridization to a nucleic acid target. PMID:28691083

MicroRNAs in Control of Stem Cells in Normal and Malignant Hematopoiesis

PubMed Central

Roden, Christine; Lu, Jun

2016-01-01

Studies on hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) have helped to establish the paradigms of normal and cancer stem cell concepts. For both HSCs and LSCs, specific gene expression programs endowed by their epigenome functionally distinguish them from their differentiated progenies. MicroRNAs (miRNAs), as a class of small non-coding RNAs, act to control post-transcriptional gene expression. Research in the past decade has yielded exciting findings elucidating the roles of miRNAs in control of multiple facets of HSC and LSC biology. Here we review recent progresses on the functions of miRNAs in HSC emergence during development, HSC switch from a fetal/neonatal program to an adult program, HSC self-renewal and quiescence, HSC aging, HSC niche, and malignant stem cells. While multiple different miRNAs regulate a diverse array of targets, two common themes emerge in HSC and LSC biology: miRNA mediated regulation of epigenetic machinery and cell signaling pathways. In addition, we propose that miRNAs themselves behave like epigenetic regulators, as they possess key biochemical and biological properties that can provide both stability and alterability to the epigenetic program. Overall, the studies of miRNAs in stem cells in the hematologic contexts not only provide key understandings to post-transcriptional gene regulation mechanisms in HSCs and LSCs, but also will lend key insights for other stem cell fields. PMID:27547713

Predicting physical properties of emerging compounds with limited physical and chemical data: QSAR model uncertainty and applicability to military munitions.

PubMed

Bennett, Erin R; Clausen, Jay; Linkov, Eugene; Linkov, Igor

2009-11-01

Reliable, up-front information on physical and biological properties of emerging materials is essential before making a decision and investment to formulate, synthesize, scale-up, test, and manufacture a new material for use in both military and civilian applications. Multiple quantitative structure-activity relationships (QSARs) software tools are available for predicting a material's physical/chemical properties and environmental effects. Even though information on emerging materials is often limited, QSAR software output is treated without sufficient uncertainty analysis. We hypothesize that uncertainty and variability in material properties and uncertainty in model prediction can be too large to provide meaningful results. To test this hypothesis, we predicted octanol water partitioning coefficients (logP) for multiple, similar compounds with limited physical-chemical properties using six different commercial logP calculators (KOWWIN, MarvinSketch, ACD/Labs, ALogP, CLogP, SPARC). Analysis was done for materials with largely uncertain properties that were similar, based on molecular formula, to military compounds (RDX, BTTN, TNT) and pharmaceuticals (Carbamazepine, Gemfibrizol). We have also compared QSAR modeling results for a well-studied pesticide and pesticide breakdown product (Atrazine, DDE). Our analysis shows variability due to structural variations of the emerging chemicals may be several orders of magnitude. The model uncertainty across six software packages was very high (10 orders of magnitude) for emerging materials while it was low for traditional chemicals (e.g. Atrazine). Thus the use of QSAR models for emerging materials screening requires extensive model validation and coupling QSAR output with available empirical data and other relevant information.

Bioactive compounds of sea cucumbers and their therapeutic effects

NASA Astrophysics Data System (ADS)

Shi, Shujuan; Feng, Wenjing; Hu, Song; Liang, Shixiu; An, Nina; Mao, Yongjun

2016-05-01

Sea cucumbers belong to the Class Holothuroidea of marine invertebrates. They are commercially valuable and prized as a food and folk medicine in Asia. Nutritionally, sea cucumbers have an impressive profile of valuable nutrients such as vitamins, minerals and amino acids. A number of unique biological and pharmacological activities/properties, including anticancer, anticoagulant/antithrombotic, antimicrobial, antioxidant, antihyperlipidemic, antihyperglycemic, anti-inflammatory, antihypertension and radioprotective, have been ascribed to various compounds isolated from sea cucumbers. The therapeutic properties and medicinal benefits of sea cucumbers can be linked to the presence of a wide array of bioactives, especially triterpene glycosides, acid mucopolysaccharide, sphingoid bases, glycolipids, fucosylated chondroitin sulfate, polysaccharides, phospholipids, cerebrosides, phosphatidylcholines, and other extracts and hydrolysates. This review highlights the valuable bioactive components as well as the multiple therapeutic properties of sea cucumbers with a view to exploring their potential uses as functional foods and a natural source of new multifunctional drugs.

Combinatorial microfluidic droplet engineering for biomimetic material synthesis

PubMed Central

Bawazer, Lukmaan A.; McNally, Ciara S.; Empson, Christopher J.; Marchant, William J.; Comyn, Tim P.; Niu, Xize; Cho, Soongwon; McPherson, Michael J.; Binks, Bernard P.; deMello, Andrew; Meldrum, Fiona C.

2016-01-01

Although droplet-based systems are used in a wide range of technologies, opportunities for systematically customizing their interface chemistries remain relatively unexplored. This article describes a new microfluidic strategy for rapidly tailoring emulsion droplet compositions and properties. The approach uses a simple platform for screening arrays of droplet-based microfluidic devices and couples this with combinatorial selection of the droplet compositions. Through the application of genetic algorithms over multiple screening rounds, droplets with target properties can be rapidly generated. The potential of this method is demonstrated by creating droplets with enhanced stability, where this is achieved by selecting carrier fluid chemistries that promote titanium dioxide formation at the droplet interfaces. The interface is a mixture of amorphous and crystalline phases, and the resulting composite droplets are biocompatible, supporting in vitro protein expression in their interiors. This general strategy will find widespread application in advancing emulsion properties for use in chemistry, biology, materials, and medicine. PMID:27730209

Graphene: from synthesis to engineering to biosensor applications

NASA Astrophysics Data System (ADS)

Singh, Jagpreet; Rathi, Aditi; Rawat, Mohit; Gupta, Manoj

2018-03-01

Graphene is a fascinating material of recent origin whose first isolation was being made possible through micromechanical cleavage of a graphite crystal. Owing to its fascinating properties, graphene has garnered significant attention in the research community for multiple applications. A number of methods have been employed for the synthesis of single-layer and multi-layer graphene. The extraordinary properties of graphene such as its Hall effect at room temperature, high surface area, tunable bandgap, high charge mobility and excellent electrical, conducting and thermal properties allow for the development of sensors of various types and also opened the doors for its use in nanoelectronics, supercapacitors and batteries. Biological aspects of graphene have also been investigated with particular emphasis on its toxicity and drug delivery. In this review, many of the salient aspects of graphene, such as from synthesis to its applications, primarily focusing on sensor applications which are of current interest, are covered.

Structure and formation of ant transportation networks

PubMed Central

Latty, Tanya; Ramsch, Kai; Ito, Kentaro; Nakagaki, Toshiyuki; Sumpter, David J. T.; Middendorf, Martin; Beekman, Madeleine

2011-01-01

Many biological systems use extensive networks for the transport of resources and information. Ants are no exception. How do biological systems achieve efficient transportation networks in the absence of centralized control and without global knowledge of the environment? Here, we address this question by studying the formation and properties of inter-nest transportation networks in the Argentine ant (Linepithema humile). We find that the formation of inter-nest networks depends on the number of ants involved in the construction process. When the number of ants is sufficient and networks do form, they tend to have short total length but a low level of robustness. These networks are topologically similar to either minimum spanning trees or Steiner networks. The process of network formation involves an initial construction of multiple links followed by a pruning process that reduces the number of trails. Our study thus illuminates the conditions under and the process by which minimal biological transport networks can be constructed. PMID:21288958

The Effect of Hypoxia on Mesenchymal Stem Cell Biology

PubMed Central

Ejtehadifar, Mostafa; Shamsasenjan, Karim; Movassaghpour, Aliakbar; Akbarzadehlaleh, Parvin; Dehdilani, Nima; Abbasi, Parvaneh; Molaeipour, Zahra; Saleh, Mahshid

2015-01-01

Although physiological and pathological role of hypoxia have been appreciated in mammalians for decades however the cellular biology of hypoxia more clarified in the past 20 years. Discovery of the transcription factor hypoxia-inducible factor (HIF)-1, in the 1990s opened a new window to investigate the mechanisms behind hypoxia. In different cellular contexts HIF-1 activation show variable results by impacting various aspects of cell biology such as cell cycle, apoptosis, differentiation and etc. Mesenchymal stem cells (MSC) are unique cells which take important role in tissue regeneration. They are characterized by self-renewal capacity, multilineage potential, and immunosuppressive property. Like so many kind of cells, hypoxia induces different responses in MSCs by HIF- 1 activation. The activation of this molecule changes the growth, multiplication, differentiation and gene expression profile of MSCs in their niche by a complex of signals. This article briefly discusses the most important effects of hypoxia in growth kinetics, signalling pathways, cytokine secretion profile and expression of chemokine receptors in different conditions. PMID:26236651

A pathway-based network analysis of hypertension-related genes

NASA Astrophysics Data System (ADS)

Wang, Huan; Hu, Jing-Bo; Xu, Chuan-Yun; Zhang, De-Hai; Yan, Qian; Xu, Ming; Cao, Ke-Fei; Zhang, Xu-Sheng

2016-02-01

Complex network approach has become an effective way to describe interrelationships among large amounts of biological data, which is especially useful in finding core functions and global behavior of biological systems. Hypertension is a complex disease caused by many reasons including genetic, physiological, psychological and even social factors. In this paper, based on the information of biological pathways, we construct a network model of hypertension-related genes of the salt-sensitive rat to explore the interrelationship between genes. Statistical and topological characteristics show that the network has the small-world but not scale-free property, and exhibits a modular structure, revealing compact and complex connections among these genes. By the threshold of integrated centrality larger than 0.71, seven key hub genes are found: Jun, Rps6kb1, Cycs, Creb312, Cdk4, Actg1 and RT1-Da. These genes should play an important role in hypertension, suggesting that the treatment of hypertension should focus on the combination of drugs on multiple genes.

Programmable DNA Hydrogels Assembled from Multidomain DNA Strands.

PubMed

Jiang, Huiling; Pan, Victor; Vivek, Skanda; Weeks, Eric R; Ke, Yonggang

2016-06-16

Hydrogels are important in biological and medical applications, such as drug delivery and tissue engineering. DNA hydrogels have attracted significant attention due to the programmability and biocompatibility of the material. We developed a series of low-cost one-strand DNA hydrogels self-assembled from single-stranded DNA monomers containing multiple palindromic domains. This new hydrogel design is simple and programmable. Thermal stability, mechanical properties, and loading capacity of these one-strand DNA hydrogels can be readily regulated by simply adjusting the DNA domains. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Three-dimensional multifunctional optical coherence tomography for skin imaging

NASA Astrophysics Data System (ADS)

Li, En; Makita, Shuichi; Hong, Young-Joo; Kasaragod, Deepa; Sasaoka, Tomoko; Yamanari, Masahiro; Sugiyama, Satoshi; Yasuno, Yoshiaki

2016-02-01

Optical coherence tomography (OCT) visualizes cross-sectional microstructures of biological tissues. Recent developments of multifunctional OCT (MF-OCT) provides multiple optical contrasts which can reveal currently unknown tissue properties. In this contribution we demonstrate multifunctional OCT specially designed for dermatological investigation. And by utilizing it to measure four different body parts of in vivo human skin, three-dimensional scattering OCT, OCT angiography, polarization uniformity tomography, and local birefringence tomography images were obtained by a single scan. They respectively contrast the structure and morphology, vasculature, melanin content and collagen traits of the tissue.

Finding novel pharmaceuticals in the systems biology era using multiple effective drug targets, phenotypic screening and knowledge of transporters: where drug discovery went wrong and how to fix it.

PubMed

Kell, Douglas B

2013-12-01

Despite the sequencing of the human genome, the rate of innovative and successful drug discovery in the pharmaceutical industry has continued to decrease. Leaving aside regulatory matters, the fundamental and interlinked intellectual issues proposed to be largely responsible for this are: (a) the move from 'function-first' to 'target-first' methods of screening and drug discovery; (b) the belief that successful drugs should and do interact solely with single, individual targets, despite natural evolution's selection for biochemical networks that are robust to individual parameter changes; (c) an over-reliance on the rule-of-5 to constrain biophysical and chemical properties of drug libraries; (d) the general abandoning of natural products that do not obey the rule-of-5; (e) an incorrect belief that drugs diffuse passively into (and presumably out of) cells across the bilayers portions of membranes, according to their lipophilicity; (f) a widespread failure to recognize the overwhelmingly important role of proteinaceous transporters, as well as their expression profiles, in determining drug distribution in and between different tissues and individual patients; and (g) the general failure to use engineering principles to model biology in parallel with performing 'wet' experiments, such that 'what if?' experiments can be performed in silico to assess the likely success of any strategy. These facts/ideas are illustrated with a reasonably extensive literature review. Success in turning round drug discovery consequently requires: (a) decent systems biology models of human biochemical networks; (b) the use of these (iteratively with experiments) to model how drugs need to interact with multiple targets to have substantive effects on the phenotype; (c) the adoption of polypharmacology and/or cocktails of drugs as a desirable goal in itself; (d) the incorporation of drug transporters into systems biology models, en route to full and multiscale systems biology models that incorporate drug absorption, distribution, metabolism and excretion; (e) a return to 'function-first' or phenotypic screening; and (f) novel methods for inferring modes of action by measuring the properties on system variables at all levels of the 'omes. Such a strategy offers the opportunity of achieving a state where we can hope to predict biological processes and the effect of pharmaceutical agents upon them. Consequently, this should both lower attrition rates and raise the rates of discovery of effective drugs substantially. © 2013 The Author Journal compilation © 2013 FEBS.

Bayesian screening for active compounds in high-dimensional chemical spaces combining property descriptors and molecular fingerprints.

PubMed

Vogt, Martin; Bajorath, Jürgen

2008-01-01

Bayesian classifiers are increasingly being used to distinguish active from inactive compounds and search large databases for novel active molecules. We introduce an approach to directly combine the contributions of property descriptors and molecular fingerprints in the search for active compounds that is based on a Bayesian framework. Conventionally, property descriptors and fingerprints are used as alternative features for virtual screening methods. Following the approach introduced here, probability distributions of descriptor values and fingerprint bit settings are calculated for active and database molecules and the divergence between the resulting combined distributions is determined as a measure of biological activity. In test calculations on a large number of compound activity classes, this methodology was found to consistently perform better than similarity searching using fingerprints and multiple reference compounds or Bayesian screening calculations using probability distributions calculated only from property descriptors. These findings demonstrate that there is considerable synergy between different types of property descriptors and fingerprints in recognizing diverse structure-activity relationships, at least in the context of Bayesian modeling.

Reduced flavin: NMR investigation of N5-H exchange mechanism, estimation of ionisation constants and assessment of properties as biological catalyst.

PubMed

Macheroux, Peter; Ghisla, Sandro; Sanner, Christoph; Rüterjans, Heinz; Müller, Franz

2005-11-25

The flavin in its FMN and FAD forms is a versatile cofactor that is involved in catalysis of most disparate types of biological reactions. These include redox reactions such as dehydrogenations, activation of dioxygen, electron transfer, bioluminescence, blue light reception, photobiochemistry (as in photolyases), redox signaling etc. Recently, hitherto unrecognized types of biological reactions have been uncovered that do not involve redox shuffles, and might involve the reduced form of the flavin as a catalyst. The present work addresses properties of reduced flavin relevant in this context. N(5)-H exchange reactions of the flavin reduced form and its pH dependence were studied using the 15N-NMR-signals of 15N-enriched, reduced flavin in the pH range from 5 to 12. The chemical shifts of the N(3) and N(5) resonances are not affected to a relevant extent in this pH range. This contrasts with the multiplicity of the N(5)-resonance, which strongly depends on pH. It is a doublet between pH 8.45 and 10.25 that coalesces into a singlet at lower and higher pH values. From the line width of the 15N(5) signal the pH-dependent rate of hydrogen exchange was deduced. The multiplicity of the 15N(5) signal and the proton exchange rates are little dependent on the buffer system used. The exchange rates allow an estimation of the pKa value of N(5)-H deprotonation in reduced flavin to be >or= 20. This value imposes specific constraints for mechanisms of flavoprotein catalysis based on this process. On the other hand the pK asymptotically equal to 4 for N(5)-H protonation (to form N(5)+-H2) would be consistent with a role of N(5)-H as a base.

Investigating dye performance and crosstalk in fluorescence enabled bioimaging using a model system

PubMed Central

Arppe, Riikka; Carro-Temboury, Miguel R.; Hempel, Casper; Vosch, Tom

2017-01-01

Detailed imaging of biological structures, often smaller than the diffraction limit, is possible in fluorescence microscopy due to the molecular size and photophysical properties of fluorescent probes. Advances in hardware and multiple providers of high-end bioimaging makes comparing images between studies and between research groups very difficult. Therefore, we suggest a model system to benchmark instrumentation, methods and staining procedures. The system we introduce is based on doped zeolites in stained polyvinyl alcohol (PVA) films: a highly accessible model system which has the properties needed to act as a benchmark in bioimaging experiments. Rather than comparing molecular probes and imaging methods in complicated biological systems, we demonstrate that the model system can emulate this complexity and can be used to probe the effect of concentration, brightness, and cross-talk of fluorophores on the detected fluorescence signal. The described model system comprises of lanthanide (III) ion doped Linde Type A zeolites dispersed in a PVA film stained with fluorophores. We tested: F18, MitoTracker Red and ATTO647N. This model system allowed comparing performance of the fluorophores in experimental conditions. Importantly, we here report considerable cross-talk of the dyes when exchanging excitation and emission settings. Additionally, bleaching was quantified. The proposed model makes it possible to test and benchmark staining procedures before these dyes are applied to more complex biological systems. PMID:29176775

Saponins from sea cucumber and their biological activities.

PubMed

Zhao, Yingcai; Xue, Changhu; Zhang, Tiantian; Wang, YuMing

2018-06-22

Sea cucumbers, belonging to the phylum Echinodermata, have been valued for centuries as a nutritious and functional food with various bioactivities. Sea cucumbers can produce highly active substances, notably saponins, the main secondary metabolites, which are the basis of their chemical defense. The saponins are mostly triterpene glycosides with triterpenes or steroid in aglycone, which possess multiple biological properties including anti-tumor, hypolipidemic activity, improvement of nonalcoholic fatty liver, inhibition of fat accumulation, anti-hyperuricemia, promotion of bone marrow hematopoiesis, anti-hypertension, etc. Sea cucumber saponins have received attention due to their rich sources, low toxicity, high efficiency, and few side effects. This review summarizes current research on the structure and activities of sea cucumber saponins based on the physiological and pharmacological activities from source, experimental models, efficacy and mechanisms, which may provide a valuable reference for the development of sea cucumber saponins.

BiologicalNetworks 2.0 - an integrative view of genome biology data

PubMed Central

2010-01-01

Background A significant problem in the study of mechanisms of an organism's development is the elucidation of interrelated factors which are making an impact on the different levels of the organism, such as genes, biological molecules, cells, and cell systems. Numerous sources of heterogeneous data which exist for these subsystems are still not integrated sufficiently enough to give researchers a straightforward opportunity to analyze them together in the same frame of study. Systematic application of data integration methods is also hampered by a multitude of such factors as the orthogonal nature of the integrated data and naming problems. Results Here we report on a new version of BiologicalNetworks, a research environment for the integral visualization and analysis of heterogeneous biological data. BiologicalNetworks can be queried for properties of thousands of different types of biological entities (genes/proteins, promoters, COGs, pathways, binding sites, and other) and their relations (interactions, co-expression, co-citations, and other). The system includes the build-pathways infrastructure for molecular interactions/relations and module discovery in high-throughput experiments. Also implemented in BiologicalNetworks are the Integrated Genome Viewer and Comparative Genomics Browser applications, which allow for the search and analysis of gene regulatory regions and their conservation in multiple species in conjunction with molecular pathways/networks, experimental data and functional annotations. Conclusions The new release of BiologicalNetworks together with its back-end database introduces extensive functionality for a more efficient integrated multi-level analysis of microarray, sequence, regulatory, and other data. BiologicalNetworks is freely available at http://www.biologicalnetworks.org. PMID:21190573

Bridging the gap between clinicians and systems biologists: from network biology to translational biomedical research.

PubMed

Jinawath, Natini; Bunbanjerdsuk, Sacarin; Chayanupatkul, Maneerat; Ngamphaiboon, Nuttapong; Asavapanumas, Nithi; Svasti, Jisnuson; Charoensawan, Varodom

2016-11-22

With the wealth of data accumulated from completely sequenced genomes and other high-throughput experiments, global studies of biological systems, by simultaneously investigating multiple biological entities (e.g. genes, transcripts, proteins), has become a routine. Network representation is frequently used to capture the presence of these molecules as well as their relationship. Network biology has been widely used in molecular biology and genetics, where several network properties have been shown to be functionally important. Here, we discuss how such methodology can be useful to translational biomedical research, where scientists traditionally focus on one or a small set of genes, diseases, and drug candidates at any one time. We first give an overview of network representation frequently used in biology: what nodes and edges represent, and review its application in preclinical research to date. Using cancer as an example, we review how network biology can facilitate system-wide approaches to identify targeted small molecule inhibitors. These types of inhibitors have the potential to be more specific, resulting in high efficacy treatments with less side effects, compared to the conventional treatments such as chemotherapy. Global analysis may provide better insight into the overall picture of human diseases, as well as identify previously overlooked problems, leading to rapid advances in medicine. From the clinicians' point of view, it is necessary to bridge the gap between theoretical network biology and practical biomedical research, in order to improve the diagnosis, prevention, and treatment of the world's major diseases.

Interferon-alpha in the treatment of multiple myeloma.

PubMed

Khoo, Teh Liane; Vangsted, Annette Juul; Joshua, Douglas; Gibson, John

2011-03-01

Interferons are soluble proteins produced naturally by cells in response to viruses. It has both anti-proliferative and immunomodulating properties and is one of the first examples of a biological response modifier use to treat the haematological malignancy multiple myeloma. Interferon has been used in this clinical practice for over thirty years. However, despite considerable efforts, numerous clinical trials and two large meta-analysis, its exact role in the management of multiple myeloma still remains unclear. Its role in the treatment of multiple myeloma has been as a single induction agent, a co-induction agent with other chemotherapy regimens, and as maintenance therapy after conventional chemotherapy or complete remission after autologous or allogeneic transplantation. Interferon as a single induction agent or co-induction agent with other chemotherapy agents appears only to have minimal benefit in myeloma. Its role as maintenance therapy in the plateau phase of myeloma also remains uncertain. More recently, the use of interferon must now compete with the "new drugs"--thalidomide, lenalidomide and bortezomib in myeloma treatment. Will there be a future role of interferon in the treatment of multiple myeloma or will interferon be resigned to the history books remains to be seen.

Albumin-based drug delivery: harnessing nature to cure disease.

PubMed

Larsen, Maja Thim; Kuhlmann, Matthias; Hvam, Michael Lykke; Howard, Kenneth A

2016-01-01

The effectiveness of a drug is dependent on accumulation at the site of action at therapeutic levels, however, challenges such as rapid renal clearance, degradation or non-specific accumulation requires drug delivery enabling technologies. Albumin is a natural transport protein with multiple ligand binding sites, cellular receptor engagement, and a long circulatory half-life due to interaction with the recycling neonatal Fc receptor. Exploitation of these properties promotes albumin as an attractive candidate for half-life extension and targeted intracellular delivery of drugs attached by covalent conjugation, genetic fusions, association or ligand-mediated association. This review will give an overview of albumin-based products with focus on the natural biological properties and molecular interactions that can be harnessed for the design of a next-generation drug delivery platform.

Complexity and diversity.

PubMed

Doebeli, Michael; Ispolatov, Iaroslav

2010-04-23

The mechanisms for the origin and maintenance of biological diversity are not fully understood. It is known that frequency-dependent selection, generating advantages for rare types, can maintain genetic variation and lead to speciation, but in models with simple phenotypes (that is, low-dimensional phenotype spaces), frequency dependence needs to be strong to generate diversity. However, we show that if the ecological properties of an organism are determined by multiple traits with complex interactions, the conditions needed for frequency-dependent selection to generate diversity are relaxed to the point where they are easily satisfied in high-dimensional phenotype spaces. Mathematically, this phenomenon is reflected in properties of eigenvalues of quadratic forms. Because all living organisms have at least hundreds of phenotypes, this casts the potential importance of frequency dependence for the origin and maintenance of diversity in a new light.

Annual grass invasion in sagebrush-steppe: The relative importance of climate, soil properties and biotic interactions

USGS Publications Warehouse

Bansal, Sheel; Sheley, Roger L.

2016-01-01

The invasion by winter-annual grasses (AGs) such as Bromus tectorum into sagebrush steppe throughout the western USA is a classic example of a biological invasion with multiple, interacting climate, soil and biotic factors driving the invasion, although few studies have examined all components together. Across a 6000-km2 area of the northern Great Basin, we conducted a field assessment of 100 climate, soil, and biotic (functional group abundances, diversity) factors at each of 90 sites that spanned an invasion gradient ranging from 0 to 100 % AG cover. We first determined which biotic and abiotic factors had the strongest correlative relationships with AGs and each resident functional group. We then used regression and structural equation modeling to explore how multiple ecological factors interact to influence AG abundance. Among biotic interactions, we observed negative relationships between AGs and biodiversity, perennial grass cover, resident species richness, biological soil crust cover and shrub density, whereas perennial and annual forb cover, tree cover and soil microbial biomass had no direct linkage to AG. Among abiotic factors, AG cover was strongly related to climate (increasing cover with increasing temperature and aridity), but had weak relationships with soil factors. Our structural equation model showed negative effects of perennial grasses and biodiversity on AG cover while integrating the negative effects of warmer climate and positive influence of belowground processes on resident functional groups. Our findings illustrate the relative importance of biotic interactions and climate on invasive abundance, while soil properties appear to have stronger relationships with resident biota than with invasives.

Toxicant content, physical properties and biological activity of waterpipe tobacco smoke and its tobacco-free alternatives

PubMed Central

Shihadeh, Alan; Schubert, Jens; Klaiany, Joanne; El Sabban, Marwan; Luch, Andreas; Saliba, Najat A

2015-01-01

Objectives Waterpipe smoking using sweetened, flavoured tobacco products has become a widespread global phenomenon. In this paper, we review chemical, physical and biological properties of waterpipe smoke. Data sources Peer-reviewed publications indexed in major databases between 1991 and 2014. Search keywords included a combination of: waterpipe, narghile, hookah, shisha along with names of chemical compounds and classes of compounds, in addition to terms commonly used in cellular biology and aerosol sizing. Study selection The search was limited to articles published in English which reported novel data on waterpipe tobacco smoke (WTS) toxicant content, biological activity or particle size and which met various criteria for analytical rigour including: method specificity and selectivity, precision, accuracy and recovery, linearity, range, and stability. Data extraction Multiple researchers reviewed the reports and collectively agreed on which data were pertinent for inclusion. Data synthesis Waterpipe smoke contains significant concentrations of toxicants thought to cause dependence, heart disease, lung disease and cancer in cigarette smokers, and includes 27 known or suspected carcinogens. Waterpipe smoke is a respirable aerosol that induces cellular responses associated with pulmonary and arterial diseases. Except nicotine, smoke generated using tobacco-free preparations marketed for ‘health conscious’ users contains the same or greater doses of toxicants, with the same cellular effects as conventional products. Toxicant yield data from the analytical laboratory are consistent with studies of exposure biomarkers in waterpipe users. Conclusions A sufficient evidence base exists to support public health interventions that highlight the fact that WTS presents a serious inhalation hazard. PMID:25666550

A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking

PubMed Central

Gilbert, David

2016-01-01

Insights gained from multilevel computational models of biological systems can be translated into real-life applications only if the model correctness has been verified first. One of the most frequently employed in silico techniques for computational model verification is model checking. Traditional model checking approaches only consider the evolution of numeric values, such as concentrations, over time and are appropriate for computational models of small scale systems (e.g. intracellular networks). However for gaining a systems level understanding of how biological organisms function it is essential to consider more complex large scale biological systems (e.g. organs). Verifying computational models of such systems requires capturing both how numeric values and properties of (emergent) spatial structures (e.g. area of multicellular population) change over time and across multiple levels of organization, which are not considered by existing model checking approaches. To address this limitation we have developed a novel approximate probabilistic multiscale spatio-temporal meta model checking methodology for verifying multilevel computational models relative to specifications describing the desired/expected system behaviour. The methodology is generic and supports computational models encoded using various high-level modelling formalisms because it is defined relative to time series data and not the models used to generate it. In addition, the methodology can be automatically adapted to case study specific types of spatial structures and properties using the spatio-temporal meta model checking concept. To automate the computational model verification process we have implemented the model checking approach in the software tool Mule (http://mule.modelchecking.org). Its applicability is illustrated against four systems biology computational models previously published in the literature encoding the rat cardiovascular system dynamics, the uterine contractions of labour, the Xenopus laevis cell cycle and the acute inflammation of the gut and lung. Our methodology and software will enable computational biologists to efficiently develop reliable multilevel computational models of biological systems. PMID:27187178

A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking.

PubMed

Pârvu, Ovidiu; Gilbert, David

2016-01-01

Insights gained from multilevel computational models of biological systems can be translated into real-life applications only if the model correctness has been verified first. One of the most frequently employed in silico techniques for computational model verification is model checking. Traditional model checking approaches only consider the evolution of numeric values, such as concentrations, over time and are appropriate for computational models of small scale systems (e.g. intracellular networks). However for gaining a systems level understanding of how biological organisms function it is essential to consider more complex large scale biological systems (e.g. organs). Verifying computational models of such systems requires capturing both how numeric values and properties of (emergent) spatial structures (e.g. area of multicellular population) change over time and across multiple levels of organization, which are not considered by existing model checking approaches. To address this limitation we have developed a novel approximate probabilistic multiscale spatio-temporal meta model checking methodology for verifying multilevel computational models relative to specifications describing the desired/expected system behaviour. The methodology is generic and supports computational models encoded using various high-level modelling formalisms because it is defined relative to time series data and not the models used to generate it. In addition, the methodology can be automatically adapted to case study specific types of spatial structures and properties using the spatio-temporal meta model checking concept. To automate the computational model verification process we have implemented the model checking approach in the software tool Mule (http://mule.modelchecking.org). Its applicability is illustrated against four systems biology computational models previously published in the literature encoding the rat cardiovascular system dynamics, the uterine contractions of labour, the Xenopus laevis cell cycle and the acute inflammation of the gut and lung. Our methodology and software will enable computational biologists to efficiently develop reliable multilevel computational models of biological systems.

Biomimetic carriers mimicking leukocyte plasma membrane to increase tumor vasculature permeability

NASA Astrophysics Data System (ADS)

Palomba, R.; Parodi, A.; Evangelopoulos, M.; Acciardo, S.; Corbo, C.; De Rosa, E.; Yazdi, I. K.; Scaria, S.; Molinaro, R.; Furman, N. E. Toledano; You, J.; Ferrari, M.; Salvatore, F.; Tasciotti, E.

2016-10-01

Recent advances in the field of nanomedicine have demonstrated that biomimicry can further improve targeting properties of current nanotechnologies while simultaneously enable carriers with a biological identity to better interact with the biological environment. Immune cells for example employ membrane proteins to target inflamed vasculature, locally increase vascular permeability, and extravasate across inflamed endothelium. Inspired by the physiology of immune cells, we recently developed a procedure to transfer leukocyte membranes onto nanoporous silicon particles (NPS), yielding Leukolike Vectors (LLV). LLV are composed of a surface coating containing multiple receptors that are critical in the cross-talk with the endothelium, mediating cellular accumulation in the tumor microenvironment while decreasing vascular barrier function. We previously demonstrated that lymphocyte function-associated antigen (LFA-1) transferred onto LLV was able to trigger the clustering of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Herein, we provide a more comprehensive analysis of the working mechanism of LLV in vitro in activating this pathway and in vivo in enhancing vascular permeability. Our results suggest the biological activity of the leukocyte membrane can be retained upon transplant onto NPS and is critical in providing the particles with complex biological functions towards tumor vasculature.

Quantification of Degeneracy in Biological Systems for Characterization of Functional Interactions Between Modules

PubMed Central

Li, Yao; Dwivedi, Gaurav; Huang, Wen; Yi, Yingfei

2012-01-01

There is an evolutionary advantage in having multiple components with overlapping functionality (i.e degeneracy) in organisms. While theoretical considerations of degeneracy have been well established in neural networks using information theory, the same concepts have not been developed for differential systems, which form the basis of many biochemical reaction network descriptions in systems biology. Here we establish mathematical definitions of degeneracy, complexity and robustness that allow for the quantification of these properties in a system. By exciting a dynamical system with noise, the mutual information associated with a selected observable output and the interacting subspaces of input components can be used to define both complexity and degeneracy. The calculation of degeneracy in a biological network is a useful metric for evaluating features such as the sensitivity of a biological network to environmental evolutionary pressure. Using a two-receptor signal transduction network, we find that redundant components will not yield high degeneracy whereas compensatory mechanisms established by pathway crosstalk will. This form of analysis permits interrogation of large-scale differential systems for non-identical, functionally equivalent features that have evolved to maintain homeostasis during disruption of individual components. PMID:22619750

Super-resolution atomic force photoactivated microscopy of biological samples (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lee, Seunghyun; Kim, Hyemin; Shin, Seungjun; Doh, Junsang; Kim, Chulhong

2017-03-01

Optical microscopy (OM) and photoacoustic microscopy (PAM) have previously been used to image the optical absorption of intercellular features of biological cells. However, the optical diffraction limit ( 200 nm) makes it difficult for these modalities to image nanoscale inner cell structures and the distribution of internal cell components. Although super-resolution fluorescence microscopy, such as stimulated emission depletion microscopy (STED) and stochastic optical reconstruction microscopy (STORM), has successfully performed nanoscale biological imaging, these modalities require the use of exogenous fluorescence agents, which are unfavorable for biological samples. Our newly developed atomic force photoactivated microscopy (AFPM) can provide optical absorption images with nanoscale lateral resolution without any exogenous contrast agents. AFPM combines conventional atomic force microscopy (AFM) and an optical excitation system, and simultaneously provides multiple contrasts, such as the topography and magnitude of optical absorption. AFPM can detect the intrinsic optical absorption of samples with 8 nm lateral resolution, easily overcoming the diffraction limit. Using the label-free AFPM system, we have successfully imaged the optical absorption properties of a single melanoma cell (B16F10) and a rosette leaf epidermal cell of Arabidopsis (ecotype Columbia (Col-0)) with nanoscale lateral resolution. The remarkable images show the melanosome distribution of a melanoma cell and the biological structures of a plant cell. AFPM provides superior imaging of optical absorption with a nanoscale lateral resolution, and it promises to become widely used in biological and chemical research.

Tunable Collagen I Hydrogels for Engineered Physiological Tissue Micro-Environments

PubMed Central

Antoine, Elizabeth E.; Vlachos, Pavlos P.; Rylander, Marissa N.

2015-01-01

Collagen I hydrogels are commonly used to mimic the extracellular matrix (ECM) for tissue engineering applications. However, the ability to design collagen I hydrogels similar to the properties of physiological tissues has been elusive. This is primarily due to the lack of quantitative correlations between multiple fabrication parameters and resulting material properties. This study aims to enable informed design and fabrication of collagen hydrogels in order to reliably and reproducibly mimic a variety of soft tissues. We developed empirical predictive models relating fabrication parameters with material and transport properties. These models were obtained through extensive experimental characterization of these properties, which include compression modulus, pore and fiber diameter, and diffusivity. Fabrication parameters were varied within biologically relevant ranges and included collagen concentration, polymerization pH, and polymerization temperature. The data obtained from this study elucidates previously unknown fabrication-property relationships, while the resulting equations facilitate informed a priori design of collagen hydrogels with prescribed properties. By enabling hydrogel fabrication by design, this study has the potential to greatly enhance the utility and relevance of collagen hydrogels in order to develop physiological tissue microenvironments for a wide range of tissue engineering applications. PMID:25822731

Multi-color phase imaging and sickle cell anemia (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hosseini, Poorya; Zhou, Renjie; Yaqoob, Zahid; So, Peter T. C.

2016-03-01

Quantitative phase measurements at multiple wavelengths has created an opportunity for exploring new avenues in phase microscopy such as enhancing imaging-depth (1), measuring hemoglobin concentrations in erythrocytes (2), and more recently in tomographic mapping of the refractive index of live cells (3). To this end, quantitative phase imaging has been demonstrated both at few selected spectral points as well as with high spectral resolution (4,5). However, most of these developed techniques compromise imaging speed, field of view, or the spectral resolution to perform interferometric measurements at multiple colors. In the specific application of quantitative phase in studying blood diseases and red blood cells, current techniques lack the required sensitivity to quantify biological properties of interest at individual cell level. Recently, we have set out to develop a stable quantitative interferometric microscope allowing for measurements of such properties for red cells without compromising field of view or speed of the measurements. The feasibility of the approach will be initially demonstrated in measuring dispersion curves of known solutions, followed by measuring biological properties of red cells in sickle cell anemia. References: 1. Mann CJ, Bingham PR, Paquit VC, Tobin KW. Quantitative phase imaging by three-wavelength digital holography. Opt Express. 2008;16(13):9753-64. 2. Park Y, Yamauchi T, Choi W, Dasari R, Feld MS. Spectroscopic phase microscopy for quantifying hemoglobin concentrations in intact red blood cells. Opt Lett. 2009;34(23):3668-70. 3. Hosseini P, Sung Y, Choi Y, Lue N, Yaqoob Z, So P. Scanning color optical tomography (SCOT). Opt Express. 2015;23(15):19752-62. 4. Jung J-H, Jang J, Park Y. Spectro-refractometry of individual microscopic objects using swept-source quantitative phase imaging. Anal Chem. 2013;85(21):10519-25. 5. Rinehart M, Zhu Y, Wax A. Quantitative phase spectroscopy. Biomed Opt Express. 2012;3(5):958-65.

Insights into resource consumption, cross-feeding, system collapse, stability and biodiversity from an artificial ecosystem

PubMed Central

Sumpter, David

2017-01-01

Community ecosystems at very different levels of biological organization often have similar properties. Coexistence of multiple species, cross-feeding, biodiversity and fluctuating population dynamics are just a few of the properties that arise in a range of ecological settings. Here we develop a bottom-up model of consumer–resource interactions, in the form of an artificial ecosystem ‘number soup’, which reflects basic properties of many bacterial and other community ecologies. We demonstrate four key properties of the number soup model: (i) communities self-organize so that all available resources are fully consumed; (ii) reciprocal cross-feeding is a common evolutionary outcome, which evolves in a number of stages, and many transitional species are involved; (iii) the evolved ecosystems are often ‘robust yet fragile’, with keystone species required to prevent the whole system from collapsing; (iv) non-equilibrium dynamics and chaotic patterns are general properties, readily generating rich biodiversity. These properties have been observed in empirical ecosystems, ranging from bacteria to rainforests. Establishing similar properties in an evolutionary model as simple as the number soup suggests that these four properties are ubiquitous features of all community ecosystems, and raises questions about how we interpret ecosystem structure in the context of natural selection. PMID:28100827

EMICORON: A multi-targeting G4 ligand with a promising preclinical profile.

PubMed

Porru, Manuela; Zizza, Pasquale; Franceschin, Marco; Leonetti, Carlo; Biroccio, Annamaria

2017-05-01

During the last decade, guanine G-rich sequences folding into G-quadruplex (G4) structures have received a lot of attention and their biological role is now a matter of large debate. Rising amounts of experimental evidence have validated several G-rich motifs as molecular targets in cancer treatment. Despite that an increasing number of small molecules has been reported to possess excellent G4 stabilizing properties, none of them has progressed through the drug-development pipeline due to their poor drug-like properties. In this context, the identification of G4 ligands with more favorable pharmacological properties and with a well-defined target activity could be fruitful for anticancer therapy application. This manuscript outlines the current state of knowledge regarding EMICORON, a G4-interactive molecule structurally and biologically similar, on the one side, to coronene and, on the other side, to a bay-monosubstituted perylene. Overall this work evidences that EMICORON, a new promising G4 ligand, possesses a marked antitumoral activity both standing alone and in combination with chemotherapeutics. Moreover, EMICORON represents a good example of multimodal class of antitumoral drug, able to simultaneously affect multiple targets participating in several distinct signaling pathways, thus simplifying the treatment modalities and improving the selectivity against cancer cells. Due to the importance of G4 forming sequences in crucial biological processes participating in tumor progression, their successful targeting with small molecules could represent a very important innovation in the development of effective therapeutic strategies against cancer. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. Copyright © 2016 Elsevier B.V. All rights reserved.

An ultra-stable single-chain insulin analog resists thermal inactivation and exhibits biological signaling duration equivalent to the native protein.

PubMed

Glidden, Michael D; Aldabbagh, Khadijah; Phillips, Nelson B; Carr, Kelley; Chen, Yen-Shan; Whittaker, Jonathan; Phillips, Manijeh; Wickramasinghe, Nalinda P; Rege, Nischay; Swain, Mamuni; Peng, Yi; Yang, Yanwu; Lawrence, Michael C; Yee, Vivien C; Ismail-Beigi, Faramarz; Weiss, Michael A

2018-01-05

Thermal degradation of insulin complicates its delivery and use. Previous efforts to engineer ultra-stable analogs were confounded by prolonged cellular signaling in vivo , of unclear safety and complicating mealtime therapy. We therefore sought an ultra-stable analog whose potency and duration of action on intravenous bolus injection in diabetic rats are indistinguishable from wild-type (WT) insulin. Here, we describe the structure, function, and stability of such an analog, a 57-residue single-chain insulin (SCI) with multiple acidic substitutions. Cell-based studies revealed native-like signaling properties with negligible mitogenic activity. Its crystal structure, determined as a novel zinc-free hexamer at 2.8 Å, revealed a native insulin fold with incomplete or absent electron density in the C domain; complementary NMR studies are described in the accompanying article. The stability of the analog (Δ G U 5.0(±0.1) kcal/mol at 25 °C) was greater than that of WT insulin (3.3(±0.1) kcal/mol). On gentle agitation, the SCI retained full activity for >140 days at 45 °C and >48 h at 75 °C. These findings indicate that marked resistance to thermal inactivation in vitro is compatible with native duration of activity in vivo Further, whereas WT insulin forms large and heterogeneous aggregates above the standard 0.6 mm pharmaceutical strength, perturbing the pharmacokinetic properties of concentrated formulations, dynamic light scattering, and size-exclusion chromatography revealed only limited SCI self-assembly and aggregation in the concentration range 1-7 mm Such a combination of favorable biophysical and biological properties suggests that SCIs could provide a global therapeutic platform without a cold chain. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Metabolic pathways for the whole community.

PubMed

Hanson, Niels W; Konwar, Kishori M; Hawley, Alyse K; Altman, Tomer; Karp, Peter D; Hallam, Steven J

2014-07-22

A convergence of high-throughput sequencing and computational power is transforming biology into information science. Despite these technological advances, converting bits and bytes of sequence information into meaningful insights remains a challenging enterprise. Biological systems operate on multiple hierarchical levels from genomes to biomes. Holistic understanding of biological systems requires agile software tools that permit comparative analyses across multiple information levels (DNA, RNA, protein, and metabolites) to identify emergent properties, diagnose system states, or predict responses to environmental change. Here we adopt the MetaPathways annotation and analysis pipeline and Pathway Tools to construct environmental pathway/genome databases (ePGDBs) that describe microbial community metabolism using MetaCyc, a highly curated database of metabolic pathways and components covering all domains of life. We evaluate Pathway Tools' performance on three datasets with different complexity and coding potential, including simulated metagenomes, a symbiotic system, and the Hawaii Ocean Time-series. We define accuracy and sensitivity relationships between read length, coverage and pathway recovery and evaluate the impact of taxonomic pruning on ePGDB construction and interpretation. Resulting ePGDBs provide interactive metabolic maps, predict emergent metabolic pathways associated with biosynthesis and energy production and differentiate between genomic potential and phenotypic expression across defined environmental gradients. This multi-tiered analysis provides the user community with specific operating guidelines, performance metrics and prediction hazards for more reliable ePGDB construction and interpretation. Moreover, it demonstrates the power of Pathway Tools in predicting metabolic interactions in natural and engineered ecosystems.

cuTauLeaping: A GPU-Powered Tau-Leaping Stochastic Simulator for Massive Parallel Analyses of Biological Systems

PubMed Central

Besozzi, Daniela; Pescini, Dario; Mauri, Giancarlo

2014-01-01

Tau-leaping is a stochastic simulation algorithm that efficiently reconstructs the temporal evolution of biological systems, modeled according to the stochastic formulation of chemical kinetics. The analysis of dynamical properties of these systems in physiological and perturbed conditions usually requires the execution of a large number of simulations, leading to high computational costs. Since each simulation can be executed independently from the others, a massive parallelization of tau-leaping can bring to relevant reductions of the overall running time. The emerging field of General Purpose Graphic Processing Units (GPGPU) provides power-efficient high-performance computing at a relatively low cost. In this work we introduce cuTauLeaping, a stochastic simulator of biological systems that makes use of GPGPU computing to execute multiple parallel tau-leaping simulations, by fully exploiting the Nvidia's Fermi GPU architecture. We show how a considerable computational speedup is achieved on GPU by partitioning the execution of tau-leaping into multiple separated phases, and we describe how to avoid some implementation pitfalls related to the scarcity of memory resources on the GPU streaming multiprocessors. Our results show that cuTauLeaping largely outperforms the CPU-based tau-leaping implementation when the number of parallel simulations increases, with a break-even directly depending on the size of the biological system and on the complexity of its emergent dynamics. In particular, cuTauLeaping is exploited to investigate the probability distribution of bistable states in the Schlögl model, and to carry out a bidimensional parameter sweep analysis to study the oscillatory regimes in the Ras/cAMP/PKA pathway in S. cerevisiae. PMID:24663957

Plastid: nucleotide-resolution analysis of next-generation sequencing and genomics data.

PubMed

Dunn, Joshua G; Weissman, Jonathan S

2016-11-22

Next-generation sequencing (NGS) informs many biological questions with unprecedented depth and nucleotide resolution. These assays have created a need for analytical tools that enable users to manipulate data nucleotide-by-nucleotide robustly and easily. Furthermore, because many NGS assays encode information jointly within multiple properties of read alignments - for example, in ribosome profiling, the locations of ribosomes are jointly encoded in alignment coordinates and length - analytical tools are often required to extract the biological meaning from the alignments before analysis. Many assay-specific pipelines exist for this purpose, but there remains a need for user-friendly, generalized, nucleotide-resolution tools that are not limited to specific experimental regimes or analytical workflows. Plastid is a Python library designed specifically for nucleotide-resolution analysis of genomics and NGS data. As such, Plastid is designed to extract assay-specific information from read alignments while retaining generality and extensibility to novel NGS assays. Plastid represents NGS and other biological data as arrays of values associated with genomic or transcriptomic positions, and contains configurable tools to convert data from a variety of sources to such arrays. Plastid also includes numerous tools to manipulate even discontinuous genomic features, such as spliced transcripts, with nucleotide precision. Plastid automatically handles conversion between genomic and feature-centric coordinates, accounting for splicing and strand, freeing users of burdensome accounting. Finally, Plastid's data models use consistent and familiar biological idioms, enabling even beginners to develop sophisticated analytical workflows with minimal effort. Plastid is a versatile toolkit that has been used to analyze data from multiple NGS assays, including RNA-seq, ribosome profiling, and DMS-seq. It forms the genomic engine of our ORF annotation tool, ORF-RATER, and is readily adapted to novel NGS assays. Examples, tutorials, and extensive documentation can be found at https://plastid.readthedocs.io .

Maca polysaccharides: A review of compositions, isolation, therapeutics and prospects.

PubMed

Li, Yujuan; Xu, Fangxue; Zheng, Mengmeng; Xi, Xiaozhi; Cui, Xiaowei; Han, Chunchao

2018-05-01

Maca polysaccharides, some of the major bioactive substances in Lepidium meyenii (Walp.) (Maca), have various biological properties, including anti-oxidant, anti-fatigue, anti-tumor, and immunomodulatory effects, as well as hepatoprotective activity and regulation function. Although many therapeutics depend on multiple structures of maca polysaccharides in addition to providing sufficient foundations for maca polysaccharide products in industrial applications, the relationships between the pharmacological effects and structures have not been established. Therefore, this article summarizes the extraction and purification methods, compositions, pharmacological effects, prospects and industrial applications of maca polysaccharides. Copyright © 2018 Elsevier B.V. All rights reserved.

A generalized graph-theoretical matrix of heterosystems and its application to the VMV procedure.

PubMed

Mozrzymas, Anna

2011-12-14

The extensions of generalized (molecular) graph-theoretical matrix and vector-matrix-vector procedure are considered. The elements of the generalized matrix are redefined in order to describe molecules containing heteroatoms and multiple bonds. The adjacency, distance, detour and reciprocal distance matrices of heterosystems, and corresponding vectors are derived from newly defined generalized graph matrix. The topological indices, which are most widely used in predicting physicochemical and biological properties/activities of various compounds, can be calculated from the new generalized vector-matrix-vector invariant. Copyright © 2011 Elsevier Ltd. All rights reserved.

Multi-layer composite mechanical modeling for the inhomogeneous biofilm mechanical behavior.

PubMed

Wang, Xiaoling; Han, Jingshi; Li, Kui; Wang, Guoqing; Hao, Mudong

2016-08-01

Experiments showed that bacterial biofilms are heterogeneous, for example, the density, the diffusion coefficient, and mechanical properties of the biofilm are different along the biofilm thickness. In this paper, we establish a multi-layer composite model to describe the biofilm mechanical inhomogeneity based on unified multiple-component cellular automaton (UMCCA) model. By using our model, we develop finite element simulation procedure for biofilm tension experiment. The failure limit and biofilm extension displacement obtained from our model agree well with experimental measurements. This method provides an alternative theory to study the mechanical inhomogeneity in biological materials.

Single-wavelength functional photoacoustic microscopy in biological tissue.

PubMed

Danielli, Amos; Favazza, Christopher P; Maslov, Konstantin; Wang, Lihong V

2011-03-01

Recently, we developed a reflection-mode relaxation photoacoustic microscope, based on saturation intensity, to measure picosecond relaxation times using a nanosecond laser. Here, using the different relaxation times of oxygenated and deoxygenated hemoglobin molecules, both possessing extremely low fluorescence quantum yields, the oxygen saturation was quantified in vivo with single-wavelength photoacoustic microscopy. All previous functional photoacoustic microscopy measurements required imaging with multiple-laser-wavelength measurements to quantify oxygen saturation. Eliminating the need for multiwavelength measurements removes the influence of spectral properties on oxygenation calculations and improves the portability and cost-effectiveness of functional or molecular photoacoustic microscopy.

Single-wavelength functional photoacoustic microscopy in biological tissue

PubMed Central

Danielli, Amos; Favazza, Christopher P.; Maslov, Konstantin; Wang, Lihong V.

2011-01-01

Recently, we developed a reflection-mode relaxation photoacoustic microscope, based on saturation intensity, to measure picosecond relaxation times using a nanosecond laser. Here, using the different relaxation times of oxygenated and deoxygenated hemoglobin molecules, both possessing extremely low fluorescence quantum yields, the oxygen saturation was quantified in vivo with single-wavelength photoacoustic microscopy. All previous functional photoacoustic microscopy measurements required imaging with multiple laser-wavelength measurements to quantify oxygen saturation. Eliminating the need for multi-wavelength measurements removes the influence of spectral properties on oxygenation calculations and improves the portability and cost-effectiveness of functional or molecular photoacoustic microscopy. PMID:21368977

Statistical Selection of Biological Models for Genome-Wide Association Analyses.

PubMed

Bi, Wenjian; Kang, Guolian; Pounds, Stanley B

2018-05-24

Genome-wide association studies have discovered many biologically important associations of genes with phenotypes. Typically, genome-wide association analyses formally test the association of each genetic feature (SNP, CNV, etc) with the phenotype of interest and summarize the results with multiplicity-adjusted p-values. However, very small p-values only provide evidence against the null hypothesis of no association without indicating which biological model best explains the observed data. Correctly identifying a specific biological model may improve the scientific interpretation and can be used to more effectively select and design a follow-up validation study. Thus, statistical methodology to identify the correct biological model for a particular genotype-phenotype association can be very useful to investigators. Here, we propose a general statistical method to summarize how accurately each of five biological models (null, additive, dominant, recessive, co-dominant) represents the data observed for each variant in a GWAS study. We show that the new method stringently controls the false discovery rate and asymptotically selects the correct biological model. Simulations of two-stage discovery-validation studies show that the new method has these properties and that its validation power is similar to or exceeds that of simple methods that use the same statistical model for all SNPs. Example analyses of three data sets also highlight these advantages of the new method. An R package is freely available at www.stjuderesearch.org/site/depts/biostats/maew. Copyright © 2018. Published by Elsevier Inc.

Fundamentals of microfluidic cell culture in controlled microenvironments†

PubMed Central

Young, Edmond W. K.; Beebe, David J.

2010-01-01

Microfluidics has the potential to revolutionize the way we approach cell biology research. The dimensions of microfluidic channels are well suited to the physical scale of biological cells, and the many advantages of microfluidics make it an attractive platform for new techniques in biology. One of the key benefits of microfluidics for basic biology is the ability to control parameters of the cell microenvironment at relevant length and time scales. Considerable progress has been made in the design and use of novel microfluidic devices for culturing cells and for subsequent treatment and analysis. With the recent pace of scientific discovery, it is becoming increasingly important to evaluate existing tools and techniques, and to synthesize fundamental concepts that would further improve the efficiency of biological research at the microscale. This tutorial review integrates fundamental principles from cell biology and local microenvironments with cell culture techniques and concepts in microfluidics. Culturing cells in microscale environments requires knowledge of multiple disciplines including physics, biochemistry, and engineering. We discuss basic concepts related to the physical and biochemical microenvironments of the cell, physicochemical properties of that microenvironment, cell culture techniques, and practical knowledge of microfluidic device design and operation. We also discuss the most recent advances in microfluidic cell culture and their implications on the future of the field. The goal is to guide new and interested researchers to the important areas and challenges facing the scientific community as we strive toward full integration of microfluidics with biology. PMID:20179823

Step by Step: Biology Undergraduates' Problem-Solving Procedures during Multiple-Choice Assessment

ERIC Educational Resources Information Center

Prevost, Luanna B.; Lemons, Paula P.

2016-01-01

This study uses the theoretical framework of domain-specific problem solving to explore the procedures students use to solve multiple-choice problems about biology concepts. We designed several multiple-choice problems and administered them on four exams. We trained students to produce written descriptions of how they solved the problem, and this…

Method and apparatus for determining nutrient stimulation of biological processes

DOEpatents

Colwell, F.S.; Geesey, G.G.; Gillis, R.J.; Lehman, R.M.

1997-11-11

A method and apparatus is described for determining the nutrients to stimulate microorganisms in a particular environment. A representative sample of microorganisms from a particular environment are contacted with multiple support means wherein each support means has intimately associated with the surface of the support means a different nutrient composition for said microorganisms in said sample. The multiple support means is allowed to remain in contact with the microorganisms in the sample for a time period sufficient to measure differences in microorganism effects for the multiple support means. Microorganism effects for the multiple support means are then measured and compared. The invention is particularly adaptable to being conducted in situ. The additional steps of regulating nutrients added to the particular environment of microorganisms can enhance the desired results. Biological systems particularly suitable for this invention are bioremediation, biologically enhanced oil recovery, biological leaching of metals, and agricultural bioprocesses. 5 figs.

Method and apparatus for determining nutrient stimulation of biological processes

DOEpatents

Colwell, Frederick S.; Geesey, Gill G.; Gillis, Richard J.; Lehman, R. Michael

1999-01-01

A method and apparatus for determining the nutrients to stimulate microorganisms in a particular environment. A representative sample of microorganisms from a particular environment are contacted with multiple support means wherein each support means has intimately associated with the surface of the support means a different nutrient composition for said microorganisms in said sample. The multiple support means is allowed to remain in contact with the microorganisms in the sample for a time period sufficient to measure difference in microorganism effects for the multiple support means. Microorganism effects for the multiple support means are then measured and compared. The invention is particularly adaptable to being conducted in situ. The additional steps of regulating nutrients added to the particular environment of microorganisms can enhance the desired results. Biological systems particularly suitable for this invention are bioremediation, biologically enhanced oil recovery, biological leaching of metals, and agricultural bioprocesses.

Method and apparatus for determining nutrient stimulation of biological processes

DOEpatents

Colwell, F.S.; Geesey, G.G.; Gillis, R.J.; Lehman, R.M.

1999-07-13

A method and apparatus are disclosed for determining the nutrients to stimulate microorganisms in a particular environment. A representative sample of microorganisms from a particular environment are contacted with multiple support means wherein each support means has intimately associated with the surface of the support means a different nutrient composition for microorganisms in the sample. The multiple support means is allowed to remain in contact with the microorganisms in the sample for a time period sufficient to measure difference in microorganism effects for the multiple support means. Microorganism effects for the multiple support means are then measured and compared. The invention is particularly adaptable to being conducted in situ. The additional steps of regulating nutrients added to the particular environment of microorganisms can enhance the desired results. Biological systems particularly suitable for this invention are bioremediation, biologically enhanced oil recovery, biological leaching of metals, and agricultural bioprocesses. 5 figs.

Method and apparatus for determining nutrient stimulation of biological processes

DOEpatents

Colwell, Frederick S.; Geesey, Gill G.; Gillis, Richard J.; Lehman, R. Michael

1997-01-01

A method and apparatus for determining the nutrients to stimulate microorganisms in a particular environment. A representative sample of microorganisms from a particular environment are contacted with multiple support means wherein each support means has intimately associated with the surface of the support means a different nutrient composition for said microorganisms in said sample. The multiple support means is allowed to remain in contact with the microorganisms in the sample for a time period sufficient to measure differences in microorganism effects for the multiple support means. Microorganism effects for the multiple support means are then measured and compared. The invention is particularly adaptable to being conducted in situ. The additional steps of regulating nutrients added to the particular environment of microorganisms can enhance the desired results. Biological systems particularly suitable for this invention are bioremediation, biologically enhanced oil recovery, biological leaching of metals, and agricultural bioprocesses.

Micromechanical properties of canine femoral articular cartilage following multiple freeze-thaw cycles.

PubMed

Peters, Abby E; Comerford, Eithne J; Macaulay, Sophie; Bates, Karl T; Akhtar, Riaz

2017-07-01

Tissue material properties are crucial to understanding their mechanical function, both in healthy and diseased states. However, in certain circumstances logistical limitations can prevent testing on fresh samples necessitating one or more freeze-thaw cycles. To date, the nature and extent to which the material properties of articular cartilage are altered by repetitive freezing have not been explored. Therefore, the aim of this study is to quantify how articular cartilage mechanical properties, measured by nanoindentation, are affected by multiple freeze-thaw cycles. Canine cartilage plugs (n = 11) from medial and lateral femoral condyles were submerged in phosphate buffered saline, stored at 3-5°C and tested using nanoindentation within 12h. Samples were then frozen at -20°C and later thawed at 3-5°C for 3h before material properties were re-tested and samples re-frozen under the same conditions. This process was repeated for all 11 samples over three freeze-thaw cycles. Overall mean and standard deviation of shear storage modulus decreased from 1.76 ± 0.78 to 1.21 ± 0.77MPa (p = 0.91), shear loss modulus from 0.42 ± 0.19 to 0.39 ± 0.17MPa (p=0.70) and elastic modulus from 5.13 ± 2.28 to 3.52 ± 2.24MPa (p = 0.20) between fresh and three freeze-thaw cycles respectively. The loss factor increased from 0.31 ± 0.38 to 0.71 ± 1.40 (p = 0.18) between fresh and three freeze-thaw cycles. Inter-sample variability spanned as much as 10.47MPa across freezing cycles and this high-level of biological variability across samples likely explains why overall mean "whole-joint" trends do not reach statistical significance across the storage conditions tested. As a result multiple freeze-thaw cycles cannot be explicitly or statistically linked to mechanical changes within the cartilage. However, the changes in material properties observed herein may be sufficient in magnitude to impact on a variety of clinical and scientific studies of cartilage, and should be considered when planning experimental protocols. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Biological activity of selenium: Revisited.

PubMed

Wrobel, Jagoda K; Power, Ronan; Toborek, Michal

2016-02-01

Selenium (Se) is an essential micronutrient that exerts multiple and complex effects on human health. Se is essential for human well-being largely due to its potent antioxidant, anti-inflammatory, and antiviral properties. The physiological functions of Se are carried out by selenoproteins, in which Se is specifically incorporated as the amino acid, selenocysteine. Importantly, both beneficial and toxic effects of Se have been reported suggesting that the mode of action of Se is strictly chemical form and concentration dependent. Additionally, there is a relatively narrow window between Se deficiency and toxicity and growing evidence suggests that Se health effects depend greatly on the baseline level of this micronutrient. Thus, Se supplementation is not an easy task and requires an individualized approach. It is essential that we continue to explore and better characterize Se containing compounds and mechanisms of action, which could be crucial for disease prevention and treatment. © 2015 International Union of Biochemistry and Molecular Biology.

3D-printing and mechanics of bio-inspired articulated and multi-material structures.

PubMed

Porter, Michael M; Ravikumar, Nakul; Barthelat, Francois; Martini, Roberto

2017-09-01

3D-printing technologies allow researchers to build simplified physical models of complex biological systems to more easily investigate their mechanics. In recent years, a number of 3D-printed structures inspired by the dermal armors of various fishes have been developed to study their multiple mechanical functionalities, including flexible protection, improved hydrodynamics, body support, or tail prehensility. Natural fish armors are generally classified according to their shape, material and structural properties as elasmoid scales, ganoid scales, placoid scales, carapace scutes, or bony plates. Each type of dermal armor forms distinct articulation patterns that facilitate different functional advantages. In this paper, we highlight recent studies that developed 3D-printed structures not only to inform the design and application of some articulated and multi-material structures, but also to explain the mechanics of the natural biological systems they mimic. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Effect of Multiple Surface Treatments on Biological Properties of Ti-6Al-4V Alloy

NASA Astrophysics Data System (ADS)

Parsikia, Farhang; Amini, Pupak; Asgari, Sirous

2014-09-01

In this research, the effect of various surface treatments including laser processing, grit blasting and anodizing on chemical structure, surface topography, and bioactivity of Ti-6Al-4V was investigated. Six groups of samples were prepared by a combination of two alternative laser processes, grit blasting and anodizing. Selected samples were first evaluated using microanalysis techniques and contact roughness testing and were then exposed to in vitro environment. Scanning electron microscopy was used to characterize the corresponding final surface morphologies. Weight measurement and atomic absorption tests were employed for determination of bioactivity limits of different surface conditions. Based on the data obtained in this study, low-energy laser processing generally yields a better biological response. The maximum bioactivity was attained in those samples exposed to a three step treatment including low-energy laser treatment followed by grit blasting and anodizing.

Microfibril-associated glycoproteins MAGP-1 and MAGP-2 in disease.

PubMed

Craft, Clarissa S; Broekelmann, Thomas J; Mecham, Robert P

2018-03-07

Microfibril-associated glycoproteins 1 and 2 (MAGP-1, MAGP-2) are protein components of extracellular matrix microfibrils. These proteins interact with fibrillin, the core component of microfibrils, and impart unique biological properties that influence microfibril function in vertebrates. MAGPs bind active forms of TGFβ and BMPs and are capable of modulating Notch signaling. Mutations in MAGP-1 or MAGP-2 have been linked to thoracic aneurysms and metabolic disease in humans. MAGP-2 has also been shown to be an important biomarker in several human cancers. Mice lacking MAGP-1 or MAGP-2 have defects in multiple organ systems, which reflects the widespread distribution of microfibrils in vertebrate tissues. This review summarizes our current understanding of the function of the MAGPs and their relationship to human disease. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Social Determinants of Population Health: A Systems Sciences Approach

PubMed Central

Fink, David S.; Keyes, Katherine M.; Cerdá, Magdalena

2016-01-01

Population distributions of health emerge from the complex interplay of health-related factors at multiple levels, from the biological to the societal level. Individuals are aggregated within social networks, affected by their locations, and influenced differently across time. From aggregations of individuals, group properties can emerge, including some exposures that are ubiquitous within populations but variant across populations. By combining a focus on social determinants of health with a conceptual framework for understanding how genetics, biology, behavior, psychology, society, and environment interact, a systems science approach can inform our understanding of the underlying causes of the unequal distribution of health across generations and populations, and can help us identify promising approaches to reduce such inequalities. In this paper, we discuss how systems science approaches have already made several substantive and methodological contributions to the study of population health from a social epidemiology perspective. PMID:27642548

A reference protocol for comparing the biocidal properties of gas plasma generating devices

NASA Astrophysics Data System (ADS)

Shaw, A.; Seri, P.; Borghi, C. A.; Shama, G.; Iza, F.

2015-12-01

Growing interest in the use of non-thermal, atmospheric pressure gas plasmas for decontamination purposes has resulted in a multiplicity of plasma-generating devices. There is currently no universally approved method of comparing the biocidal performance of such devices and in the work described here spores of the Gram positive bacterium Bacillus subtilis (ATCC 6633) are proposed as a suitable reference biological agent. In order to achieve consistency in the form in which the biological agent in question is presented to the plasma, a polycarbonate membrane loaded with a monolayer of spores is proposed. The advantages of the proposed protocol are evaluated by comparing inactivation tests in which an alternative microorganism (methicillin resistant Staphylococcus aureus—MRSA) and the widely-used sample preparation technique of directly pipetting cell suspensions onto membranes are employed. In all cases, inactivation tests with either UV irradiation or plasma exposure were more reproducible when the proposed protocol was followed.

A novel and rapid method for obtaining high titre intact prion strains from mammalian brain.

PubMed

Wenborn, Adam; Terry, Cassandra; Gros, Nathalie; Joiner, Susan; D'Castro, Laura; Panico, Silvia; Sells, Jessica; Cronier, Sabrina; Linehan, Jacqueline M; Brandner, Sebastian; Saibil, Helen R; Collinge, John; Wadsworth, Jonathan D F

2015-05-07

Mammalian prions exist as multiple strains which produce characteristic and highly reproducible phenotypes in defined hosts. How this strain diversity is encoded by a protein-only agent remains one of the most interesting and challenging questions in biology with wide relevance to understanding other diseases involving the aggregation or polymerisation of misfolded host proteins. Progress in understanding mammalian prion strains has however been severely limited by the complexity and variability of the methods used for their isolation from infected tissue and no high resolution structures have yet been reported. Using high-throughput cell-based prion bioassay to re-examine prion purification from first principles we now report the isolation of prion strains to exceptional levels of purity from small quantities of infected brain and demonstrate faithful retention of biological and biochemical strain properties. The method's effectiveness and simplicity should facilitate its wide application and expedite structural studies of prions.

A novel and rapid method for obtaining high titre intact prion strains from mammalian brain

PubMed Central

Wenborn, Adam; Terry, Cassandra; Gros, Nathalie; Joiner, Susan; D’Castro, Laura; Panico, Silvia; Sells, Jessica; Cronier, Sabrina; Linehan, Jacqueline M.; Brandner, Sebastian; Saibil, Helen R.; Collinge, John; Wadsworth, Jonathan D. F.

2015-01-01

Mammalian prions exist as multiple strains which produce characteristic and highly reproducible phenotypes in defined hosts. How this strain diversity is encoded by a protein-only agent remains one of the most interesting and challenging questions in biology with wide relevance to understanding other diseases involving the aggregation or polymerisation of misfolded host proteins. Progress in understanding mammalian prion strains has however been severely limited by the complexity and variability of the methods used for their isolation from infected tissue and no high resolution structures have yet been reported. Using high-throughput cell-based prion bioassay to re-examine prion purification from first principles we now report the isolation of prion strains to exceptional levels of purity from small quantities of infected brain and demonstrate faithful retention of biological and biochemical strain properties. The method’s effectiveness and simplicity should facilitate its wide application and expedite structural studies of prions. PMID:25950908

Albumin in chronic liver disease: structure, functions and therapeutic implications.

PubMed

Spinella, Rosaria; Sawhney, Rohit; Jalan, Rajiv

2016-01-01

Human serum albumin is a critical plasma protein produced by the liver with a number of accepted clinical indications in chronic liver disease including management of circulatory and renal dysfunction in patients with ascites. Advanced cirrhosis is characterised by reduced albumin concentration as well as impaired albumin function as a result of specific structural changes and oxidative damage. Traditionally, the biologic and therapeutic role of albumin in liver disease was attributed to its oncotic effects but it is now understood that albumin has a wide range of other important physiologic functions such as immunomodulation, endothelial stabilisation, antioxidant effects and binding multiple drugs, toxins and other molecules. This review discusses the multifunctional properties of albumin and, in particular, the biologic and clinical implications of structural and functional changes of albumin that are associated with cirrhosis. Based on these insights, we explore the current and potential future therapeutic uses of albumin in liver disease.

The great descriptor melting pot: mixing descriptors for the common good of QSAR models.

PubMed

Tseng, Yufeng J; Hopfinger, Anton J; Esposito, Emilio Xavier

2012-01-01

The usefulness and utility of QSAR modeling depends heavily on the ability to estimate the values of molecular descriptors relevant to the endpoints of interest followed by an optimized selection of descriptors to form the best QSAR models from a representative set of the endpoints of interest. The performance of a QSAR model is directly related to its molecular descriptors. QSAR modeling, specifically model construction and optimization, has benefited from its ability to borrow from other unrelated fields, yet the molecular descriptors that form QSAR models have remained basically unchanged in both form and preferred usage. There are many types of endpoints that require multiple classes of descriptors (descriptors that encode 1D through multi-dimensional, 4D and above, content) needed to most fully capture the molecular features and interactions that contribute to the endpoint. The advantages of QSAR models constructed from multiple, and different, descriptor classes have been demonstrated in the exploration of markedly different, and principally biological systems and endpoints. Multiple examples of such QSAR applications using different descriptor sets are described and that examined. The take-home-message is that a major part of the future of QSAR analysis, and its application to modeling biological potency, ADME-Tox properties, general use in virtual screening applications, as well as its expanding use into new fields for building QSPR models, lies in developing strategies that combine and use 1D through nD molecular descriptors.

Effect of surface topographic features on the optical properties of skin: a phantom study

NASA Astrophysics Data System (ADS)

Liu, Guangli; Chen, Jianfeng; Zhao, Zuhua; Zhao, Gang; Dong, Erbao; Chu, Jiaru; Xu, Ronald X.

2016-10-01

Tissue-simulating phantoms are used to validate and calibrate optical imaging systems and to understand light transport in biological tissue. Light propagation in a strongly turbid medium such as skin tissue experiences multiple scattering and diffuse reflection from the surface. Surface roughness introduces phase shifts and optical path length differences for light which is scattered within the skin tissue and reflected from the surface. In this paper, we study the effect of mismatched surface roughness on optical measurement and subsequent determination of optical properties of skin tissue. A series of phantoms with controlled surface features and optical properties corresponding to normal human skin are fabricated. The fabrication of polydimethylsiloxane (PDMS) phantoms with known surface roughness follows a standard soft lithography process. Surface roughness of skin-simulating phantoms are measured with Bruker stylus profiler. The diffuse reflectance of the phantom is validated by a UV/VIS spectrophotometer. The results show that surface texture and roughness have considerable influence on the optical characteristics of skin. This study suggests that surface roughness should be considered as an important contributing factor for the determination of tissue optical properties.

Protection of therapeutic antibodies from visible light induced degradation: Use safe light in manufacturing and storage.

PubMed

Du, Cheng; Barnett, Gregory; Borwankar, Ameya; Lewandowski, Angela; Singh, Nripen; Ghose, Sanchayita; Borys, Michael; Li, Zheng Jian

2018-06-01

As macromolecules, biologics are susceptible to light exposure, which induces oxidation of multiple amino acid residues including tryptophan, tyrosine, phenylalanine, cysteine and methionine. Pertaining to safety, efficacy and potency, light-induced oxidation of biologics has been widely studied and necessary precautions need to be taken during biologics manufacturing process, drug substance and products handling and storage. Proteins will degrade to varying extents depending on the protein properties, degradation pathways, formulation compositions and type of light source. In addition to UV light, which has been widely known to degrade proteins, visible light from indoor fluorescent lighting also can mediate protein degradation. In this report, we examine and identify wavelengths in the visual spectrum (400-700 nm) that can cause monoclonal antibody and histidine buffer degradation. Installation of safe lights which exclude the identified damaging wavelengths from visible spectra in manufacturing and storage areas can provide a balance between lighting requirement for human operators and their safety and conservation of product quality. Copyright © 2018 Elsevier B.V. All rights reserved.

When one model is not enough: combining epistemic tools in systems biology.

PubMed

Green, Sara

2013-06-01

In recent years, the philosophical focus of the modeling literature has shifted from descriptions of general properties of models to an interest in different model functions. It has been argued that the diversity of models and their correspondingly different epistemic goals are important for developing intelligible scientific theories (Leonelli, 2007; Levins, 2006). However, more knowledge is needed on how a combination of different epistemic means can generate and stabilize new entities in science. This paper will draw on Rheinberger's practice-oriented account of knowledge production. The conceptual repertoire of Rheinberger's historical epistemology offers important insights for an analysis of the modelling practice. I illustrate this with a case study on network modeling in systems biology where engineering approaches are applied to the study of biological systems. I shall argue that the use of multiple representational means is an essential part of the dynamic of knowledge generation. It is because of-rather than in spite of-the diversity of constraints of different models that the interlocking use of different epistemic means creates a potential for knowledge production. Copyright © 2013 Elsevier Ltd. All rights reserved.

Use of mutation spectra analysis software.

PubMed

Rogozin, I; Kondrashov, F; Glazko, G

2001-02-01

The study and comparison of mutation(al) spectra is an important problem in molecular biology, because these spectra often reflect on important features of mutations and their fixation. Such features include the interaction of DNA with various mutagens, the function of repair/replication enzymes, and properties of target proteins. It is known that mutability varies significantly along nucleotide sequences, such that mutations often concentrate at certain positions, called "hotspots," in a sequence. In this paper, we discuss in detail two approaches for mutation spectra analysis: the comparison of mutation spectra with a HG-PUBL program, (FTP: sunsite.unc.edu/pub/academic/biology/dna-mutations/hyperg) and hotspot prediction with the CLUSTERM program (www.itba.mi.cnr.it/webmutation; ftp.bionet.nsc.ru/pub/biology/dbms/clusterm.zip). Several other approaches for mutational spectra analysis, such as the analysis of a target protein structure, hotspot context revealing, multiple spectra comparisons, as well as a number of mutation databases are briefly described. Mutation spectra in the lacI gene of E. coli and the human p53 gene are used for illustration of various difficulties of such analysis. Copyright 2001 Wiley-Liss, Inc.

Resveratrol Oligomers for the Prevention and Treatment of Cancers

PubMed Central

Xue, You-Qiu; Di, Jin-Ming; Luo, Yun; Cheng, Ke-Jun; Wei, Xing

2014-01-01

Resveratrol (3,4′,5-trihydroxystilbene) is a naturally derived phytoalexin stilbene isolated from grapes and other plants, playing an important role in human health and is well known for its extensive bioactivities, such as antioxidation, anti-inflammatory, anticancer. In addition to resveratrol, scientists also pay attention to resveratrol oligomers, derivatives of resveratrol, which are characterized by the polymerization of two to eight, or even more resveratrol units, and are the largest group of oligomeric stilbenes. Resveratrol oligomers have multiple beneficial properties, of which some are superior in activity, stability, and selectivity compared with resveratrol. The complicated structures and diverse biological activities are of significant interest for drug research and development and may provide promising prospects as cancer preventive and therapeutical agents. This review presents an overview on preventive or anticancer properties of resveratrol oligomers. PMID:24799982

Recombinant Collagenlike Proteins

NASA Technical Reports Server (NTRS)

Fertala, Andzej

2007-01-01

A group of collagenlike recombinant proteins containing high densities of biologically active sites has been invented. The method used to express these proteins is similar to a method of expressing recombinant procollagens and collagens described in U. S. Patent 5,593,859, "Synthesis of human procollagens and collagens in recombinant DNA systems." Customized collagenous proteins are needed for biomedical applications. In particular, fibrillar collagens are attractive for production of matrices needed for tissue engineering and drug delivery. Prior to this invention, there was no way of producing customized collagenous proteins for these and other applications. Heretofore, collagenous proteins have been produced by use of such biological systems as yeasts, bacteria, and transgenic animals and plants. These products are normal collagens that can also be extracted from such sources as tendons, bones, and hides. These products cannot be made to consist only of biologically active, specific amino acid sequences that may be needed for specific applications. Prior to this invention, it had been established that fibrillar collagens consist of domains that are responsible for such processes as interaction with cells, binding of growth factors, and interaction with a number of structural proteins present in the extracellular matrix. A normal collagen consists of a sequence of domains that can be represented by a corresponding sequence of labels, e.g., D1D2D3D4. A collagenlike protein of the present invention contains regions of collagen II that contain multiples of a single domain (e.g., D1D1D1D1 or D4D4D4D4) chosen for its specific biological activity. By virtue of the multiplicity of the chosen domain, the density of sites having that specific biological activity is greater than it is in a normal collagen. A collagenlike protein according to this invention can thus be made to have properties that are necessary for tissue engineering.

Enhanced tumor retention of a radiohalogen label for site-specific modification of antibodies.

PubMed

Boswell, C Andrew; Marik, Jan; Elowson, Michael J; Reyes, Noe A; Ulufatu, Sheila; Bumbaca, Daniela; Yip, Victor; Mundo, Eduardo E; Majidy, Nicholas; Van Hoy, Marjie; Goriparthi, Saritha N; Trias, Anthony; Gill, Herman S; Williams, Simon P; Junutula, Jagath R; Fielder, Paul J; Khawli, Leslie A

2013-12-12

A known limitation of iodine radionuclides for labeling and biological tracking of receptor targeted proteins is the tendency of iodotyrosine to rapidly diffuse from cells following endocytosis and lysosomal degradation. In contrast, radiometal-chelate complexes such as indium-111-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (In-111-DOTA) accumulate within target cells due to the residualizing properties of the polar, charged metal-chelate-amino acid adduct. Iodine radionuclides boast a diversity of nuclear properties and chemical means for incorporation, prompting efforts to covalently link radioiodine with residualizing molecules. Herein, we describe the Ugi-assisted synthesis of [I-125]HIP-DOTA, a 4-hydroxy-3-iodophenyl (HIP) derivative of DOTA, and demonstration of its residualizing properties in a murine xenograft model. Overall, this study displays the power of multicomponent synthesis to yield a versatile radioactive probe for antibodies across multiple therapeutic areas with potential applications in both preclinical biodistribution studies and clinical radioimmunotherapies.

Molecular dynamics simulations of a DMSO/water mixture using the AMBER force field.

PubMed

Stachura, Slawomir S; Malajczuk, Chris J; Mancera, Ricardo L

2018-06-25

Due to its protective properties of biological samples at low temperatures and under desiccation, dimethyl sulfoxide (DMSO) in aqueous solutions has been studied widely by many experimental approaches and molecular dynamics (MD) simulations. In the case of the latter, AMBER is among the most commonly used force fields for simulations of biomolecular systems; however, the parameters for DMSO published by Fox and Kollman in 1998 have only been tested for pure liquid DMSO. We have conducted an MD simulation study of DMSO in a water mixture and computed several structural and dynamical properties such as of the mean density, self-diffusion coefficient, hydrogen bonding and DMSO and water ordering. The AMBER force field of DMSO is seen to reproduce well most of the experimental properties of DMSO in water, with the mixture displaying strong and specific water ordering, as observed in experiments and multiple other MD simulations with other non-polarizable force fields. Graphical abstract Hydration structure within hydrogen-bonding distance around a DMSOmolecule.

Mushroom Polysaccharides: Chemistry and Antiobesity, Antidiabetes, Anticancer, and Antibiotic Properties in Cells, Rodents, and Humans.

PubMed

Friedman, Mendel

2016-11-29

More than 2000 species of edible and/or medicinal mushrooms have been identified to date, many of which are widely consumed, stimulating much research on their health-promoting properties. These properties are associated with bioactive compounds produced by the mushrooms, including polysaccharides. Although β-glucans (homopolysaccharides) are believed to be the major bioactive polysaccharides of mushrooms, other types of mushroom polysaccharides (heteropolysaccharides) also possess biological properties. Here we survey the chemistry of such health-promoting polysaccharides and their reported antiobesity and antidiabetic properties as well as selected anticarcinogenic, antimicrobial, and antiviral effects that demonstrate their multiple health-promoting potential. The associated antioxidative, anti-inflammatory, and immunomodulating activities in fat cells, rodents, and humans are also discussed. The mechanisms of action involve the gut microbiota, meaning the polysaccharides act as prebiotics in the digestive system. Also covered here are the nutritional, functional food, clinical, and epidemiological studies designed to assess the health-promoting properties of polysaccharides, individually and as blended mixtures, against obesity, diabetes, cancer, and infectious diseases, and suggestions for further research. The collated information and suggested research needs might guide further studies needed for a better understanding of the health-promoting properties of mushroom polysaccharides and enhance their use to help prevent and treat human chronic diseases.

Mushroom Polysaccharides: Chemistry and Antiobesity, Antidiabetes, Anticancer, and Antibiotic Properties in Cells, Rodents, and Humans

PubMed Central

Friedman, Mendel

2016-01-01

More than 2000 species of edible and/or medicinal mushrooms have been identified to date, many of which are widely consumed, stimulating much research on their health-promoting properties. These properties are associated with bioactive compounds produced by the mushrooms, including polysaccharides. Although β-glucans (homopolysaccharides) are believed to be the major bioactive polysaccharides of mushrooms, other types of mushroom polysaccharides (heteropolysaccharides) also possess biological properties. Here we survey the chemistry of such health-promoting polysaccharides and their reported antiobesity and antidiabetic properties as well as selected anticarcinogenic, antimicrobial, and antiviral effects that demonstrate their multiple health-promoting potential. The associated antioxidative, anti-inflammatory, and immunomodulating activities in fat cells, rodents, and humans are also discussed. The mechanisms of action involve the gut microbiota, meaning the polysaccharides act as prebiotics in the digestive system. Also covered here are the nutritional, functional food, clinical, and epidemiological studies designed to assess the health-promoting properties of polysaccharides, individually and as blended mixtures, against obesity, diabetes, cancer, and infectious diseases, and suggestions for further research. The collated information and suggested research needs might guide further studies needed for a better understanding of the health-promoting properties of mushroom polysaccharides and enhance their use to help prevent and treat human chronic diseases. PMID:28231175

Photoelectron Spectroscopy and Density Functional Theory Studies of Iron Sulfur (FeS)m- (m = 2-8) Cluster Anions: Coexisting Multiple Spin States.

PubMed

Yin, Shi; Bernstein, Elliot R

2017-10-05

Iron sulfur cluster anions (FeS) m - (m = 2-8) are studied by photoelectron spectroscopy (PES) at 3.492 eV (355 nm) and 4.661 eV (266 nm) photon energies, and by density functional theory (DFT) calculations. The most probable structures and ground state spin multiplicities for (FeS) m - (m = 2-8) clusters are tentatively assigned through a comparison of their theoretical and experiment first vertical detachment energy (VDE) values. Many spin states lie within 0.5 eV of the ground spin state for the larger (FeS) m - (m ≥ 4) clusters. Theoretical VDEs of these low lying spin states are in good agreement with the experimental VDE values. Therefore, multiple spin states of each of these iron sulfur cluster anions probably coexist under the current experimental conditions. Such available multiple spin states must be considered when evaluating the properties and behavior of these iron sulfur clusters in real chemical and biological systems. The experimental first VDEs of (FeS) m - (m = 1-8) clusters are observed to change with the cluster size (number m). The first VDE trends noted can be related to the different properties of the highest singly occupied molecular orbitals (NBO, HSOMOs) of each cluster anion. The changing nature of the NBO/HSOMO of these (FeS) m - (m = 1-8) clusters from a p orbital on S, to a d orbital on Fe, and to an Fe-Fe bonding orbital is probably responsible for the observed increasing trend for their first VDEs with respect to m.

Environmental Consequences of an Emerging Biosphere

NASA Technical Reports Server (NTRS)

DesMarais, David J.

2003-01-01

It seems feasible to detect biological signatures ("biosignatures") in other planetary systems using the tools of astronomy. There are at least two types of biosignatures; spectral and/or polarization features created by biological products, and electromagnetic signals created by technology. The latter example of a biosignature requires SETI-like searches. This presentation addresses only spectral signatures of biological products and properties of habitable planets. Spectral biosignatures are indeed promising targets for near-term exploration. They can arise from organic constituents (e.g., vegetation) and/or inorganic products (e.g., atmospheric O2). Features originating from a planet's surface are likely to be localized in specific regions, whereas gaseous biosignatures can become globally distributed by atmospheric circulation. Biosignatures should be most abundant within environments that are, or once were, habitable. We currently believe that habitable environments necessarily provide Liquid water and biochemically useful energy. However, we do not yet fully comprehend the diversity of features that might arise within these environments that are non-biological in origin, yet mimic biosignatures. For example, atmospheres reflect the events leading to their origins as well as a host of ongoing planetary processes that might include biological activity. We are persuaded that abundant atmospheric oxygen in an environment with abundant liquid water constitutes definitive evidence of life. However, our own early biosphere thrived for more than a billion years in the absence of abundant atmospheric oxygen. The production of other, more reduced, gaseous biomarkers of "young" and/or anaerobic biospheres has not been systematically studied. Biological gas production is strongly controlled by the structure and function of microbial ecosystems. Investigations of microbial ecosystems that are close analogs of ancient communities offer multiple benefits. Such studies can interpret the production of the most important biomarker gases, while simultaneously helping us to understand the formidable array of ecological processes that guided early biological evolution. Astrobiologists must recognize those aspects of biosignatures that truly reflect the most fundamental, and therefore universal, properties of life. We must learn how the environment can modify biosignatures, and how technology can enable an array of biosignatures to be detected remotely within realistic budgetary constraints

The evolvability of programmable hardware.

PubMed

Raman, Karthik; Wagner, Andreas

2011-02-06

In biological systems, individual phenotypes are typically adopted by multiple genotypes. Examples include protein structure phenotypes, where each structure can be adopted by a myriad individual amino acid sequence genotypes. These genotypes form vast connected 'neutral networks' in genotype space. The size of such neutral networks endows biological systems not only with robustness to genetic change, but also with the ability to evolve a vast number of novel phenotypes that occur near any one neutral network. Whether technological systems can be designed to have similar properties is poorly understood. Here we ask this question for a class of programmable electronic circuits that compute digital logic functions. The functional flexibility of such circuits is important in many applications, including applications of evolutionary principles to circuit design. The functions they compute are at the heart of all digital computation. We explore a vast space of 10(45) logic circuits ('genotypes') and 10(19) logic functions ('phenotypes'). We demonstrate that circuits that compute the same logic function are connected in large neutral networks that span circuit space. Their robustness or fault-tolerance varies very widely. The vicinity of each neutral network contains circuits with a broad range of novel functions. Two circuits computing different functions can usually be converted into one another via few changes in their architecture. These observations show that properties important for the evolvability of biological systems exist in a commercially important class of electronic circuitry. They also point to generic ways to generate fault-tolerant, adaptable and evolvable electronic circuitry.

The evolvability of programmable hardware

PubMed Central

Raman, Karthik; Wagner, Andreas

2011-01-01

In biological systems, individual phenotypes are typically adopted by multiple genotypes. Examples include protein structure phenotypes, where each structure can be adopted by a myriad individual amino acid sequence genotypes. These genotypes form vast connected ‘neutral networks’ in genotype space. The size of such neutral networks endows biological systems not only with robustness to genetic change, but also with the ability to evolve a vast number of novel phenotypes that occur near any one neutral network. Whether technological systems can be designed to have similar properties is poorly understood. Here we ask this question for a class of programmable electronic circuits that compute digital logic functions. The functional flexibility of such circuits is important in many applications, including applications of evolutionary principles to circuit design. The functions they compute are at the heart of all digital computation. We explore a vast space of 1045 logic circuits (‘genotypes’) and 1019 logic functions (‘phenotypes’). We demonstrate that circuits that compute the same logic function are connected in large neutral networks that span circuit space. Their robustness or fault-tolerance varies very widely. The vicinity of each neutral network contains circuits with a broad range of novel functions. Two circuits computing different functions can usually be converted into one another via few changes in their architecture. These observations show that properties important for the evolvability of biological systems exist in a commercially important class of electronic circuitry. They also point to generic ways to generate fault-tolerant, adaptable and evolvable electronic circuitry. PMID:20534598

Examining the Effect of Multiple Writing Tasks on Year 10 Biology Students' Understandings of Cell and Molecular Biology Concepts

ERIC Educational Resources Information Center

Hand, Brian; Hohenshell, Liesl; Prain, Vaughan

2007-01-01

This paper reports on a study that examined the cumulative effects on students' learning of science, and perceptions of the role of writing in learning, when the students engaged in multiple writing tasks with planning strategy support. The study was conducted with Year 10 biology students who completed two consecutive units on Cells and Molecular…

Body and Soul: Do Children Distinguish between Foods When Generalizing Biological and Psychological Properties?

ERIC Educational Resources Information Center

Thibaut, Jean-Pierre; Nguyen, Simone P.; Murphy, Gregory L.

2016-01-01

Research Findings: In 2 experiments, we tested whether children generalize psychological and biological properties to novel foods. We used an induction task in which a property (either biological or psychological) was associated with a target food. Children were then asked whether a taxonomically related and a script-related food would also have…

Performance of a lookup table-based approach for measuring tissue optical properties with diffuse optical spectroscopy

NASA Astrophysics Data System (ADS)

Nichols, Brandon S.; Rajaram, Narasimhan; Tunnell, James W.

2012-05-01

Diffuse optical spectroscopy (DOS) provides a powerful tool for fast and noninvasive disease diagnosis. The ability to leverage DOS to accurately quantify tissue optical parameters hinges on the model used to estimate light-tissue interaction. We describe the accuracy of a lookup table (LUT)-based inverse model for measuring optical properties under different conditions relevant to biological tissue. The LUT is a matrix of reflectance values acquired experimentally from calibration standards of varying scattering and absorption properties. Because it is based on experimental values, the LUT inherently accounts for system response and probe geometry. We tested our approach in tissue phantoms containing multiple absorbers, different sizes of scatterers, and varying oxygen saturation of hemoglobin. The LUT-based model was able to extract scattering and absorption properties under most conditions with errors of less than 5 percent. We demonstrate the validity of the lookup table over a range of source-detector separations from 0.25 to 1.48 mm. Finally, we describe the rapid fabrication of a lookup table using only six calibration standards. This optimized LUT was able to extract scattering and absorption properties with average RMS errors of 2.5 and 4 percent, respectively.

Engineering entrainment and adaptation in limit cycle systems : From biological inspiration to applications in robotics.

PubMed

Buchli, Jonas; Righetti, Ludovic; Ijspeert, Auke Jan

2006-12-01

Periodic behavior is key to life and is observed in multiple instances and at multiple time scales in our metabolism, our natural environment, and our engineered environment. A natural way of modeling or generating periodic behavior is done by using oscillators, i.e., dynamical systems that exhibit limit cycle behavior. While there is extensive literature on methods to analyze such dynamical systems, much less work has been done on methods to synthesize an oscillator to exhibit some specific desired characteristics. The goal of this article is twofold: (1) to provide a framework for characterizing and designing oscillators and (2) to review how classes of well-known oscillators can be understood and related to this framework. The basis of the framework is to characterize oscillators in terms of their fundamental temporal and spatial behavior and in terms of properties that these two behaviors can be designed to exhibit. This focus on fundamental properties is important because it allows us to systematically compare a large variety of oscillators that might at first sight appear very different from each other. We identify several specifications that are useful for design, such as frequency-locking behavior, phase-locking behavior, and specific output signal shape. We also identify two classes of design methods by which these specifications can be met, namely offline methods and online methods. By relating these specifications to our framework and by presenting several examples of how oscillators have been designed in the literature, this article provides a useful methodology and toolbox for designing oscillators for a wide range of purposes. In particular, the focus on synthesis of limit cycle dynamical systems should be useful both for engineering and for computational modeling of physical or biological phenomena.

Towards fast, rigorous and efficient conformational sampling of biomolecules: Advances in accelerated molecular dynamics.

PubMed

Doshi, Urmi; Hamelberg, Donald

2015-05-01

Accelerated molecular dynamics (aMD) has been proven to be a powerful biasing method for enhanced sampling of biomolecular conformations on general-purpose computational platforms. Biologically important long timescale events that are beyond the reach of standard molecular dynamics can be accessed without losing the detailed atomistic description of the system in aMD. Over other biasing methods, aMD offers the advantages of tuning the level of acceleration to access the desired timescale without any advance knowledge of the reaction coordinate. Recent advances in the implementation of aMD and its applications to small peptides and biological macromolecules are reviewed here along with a brief account of all the aMD variants introduced in the last decade. In comparison to the original implementation of aMD, the recent variant in which all the rotatable dihedral angles are accelerated (RaMD) exhibits faster convergence rates and significant improvement in statistical accuracy of retrieved thermodynamic properties. RaMD in conjunction with accelerating diffusive degrees of freedom, i.e. dual boosting, has been rigorously tested for the most difficult conformational sampling problem, protein folding. It has been shown that RaMD with dual boosting is capable of efficiently sampling multiple folding and unfolding events in small fast folding proteins. RaMD with the dual boost approach opens exciting possibilities for sampling multiple timescales in biomolecules. While equilibrium properties can be recovered satisfactorily from aMD-based methods, directly obtaining dynamics and kinetic rates for larger systems presents a future challenge. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Copyright © 2014 Elsevier B.V. All rights reserved.

Diurnal changes in ocean color in coastal waters

NASA Astrophysics Data System (ADS)

Arnone, Robert; Vandermeulen, Ryan; Ladner, Sherwin; Ondrusek, Michael; Kovach, Charles; Yang, Haoping; Salisbury, Joseph

2016-05-01

Coastal processes can change on hourly time scales in response to tides, winds and biological activity, which can influence the color of surface waters. These temporal and spatial ocean color changes require satellite validation for applications using bio-optical products to delineate diurnal processes. The diurnal color change and capability for satellite ocean color response were determined with in situ and satellite observations. Hourly variations in satellite ocean color are dependent on several properties which include: a) sensor characterization b) advection of water masses and c) diurnal response of biological and optical water properties. The in situ diurnal changes in ocean color in a dynamic turbid coastal region in the northern Gulf of Mexico were characterized using above water spectral radiometry from an AErosol RObotic NETwork (AERONET -WavCIS CSI-06) site that provides up to 8-10 observations per day (in 15-30 minute increments). These in situ diurnal changes were used to validate and quantify natural bio-optical fluctuations in satellite ocean color measurements. Satellite capability to detect changes in ocean color was characterized by using overlapping afternoon orbits of the VIIRS-NPP ocean color sensor within 100 minutes. Results show the capability of multiple satellite observations to monitor hourly color changes in dynamic coastal regions that are impacted by tides, re-suspension, and river plume dispersion. Hourly changes in satellite ocean color were validated with in situ observation on multiple occurrences during different times of the afternoon. Also, the spatial variability of VIIRS diurnal changes shows the occurrence and displacement of phytoplankton blooms and decay during the afternoon period. Results suggest that determining the temporal and spatial changes in a color / phytoplankton bloom from the morning to afternoon time period will require additional satellite coverage periods in the coastal zone.

Physical approaches to biomaterial design

PubMed Central

Mitragotri, Samir; Lahann, Joerg

2009-01-01

The development of biomaterials for drug delivery, tissue engineering and medical diagnostics has traditionally been based on new chemistries. However, there is growing recognition that the physical as well as the chemical properties of materials can regulate biological responses. Here, we review this transition with regard to selected physical properties including size, shape, mechanical properties, surface texture and compartmentalization. In each case, we present examples demonstrating the significance of these properties in biology. We also discuss synthesis methods and biological applications for designer biomaterials, which offer unique physical properties. PMID:19096389

Pharmaceutical entanglements: an analysis of the multiple determinants of ADHD medication effects in a Chilean school

PubMed Central

Rojas Navarro, Sebastian; Vrecko, Scott

2017-01-01

ABSTRACT This article draws upon findings from ethnographic fieldwork conducted in a Chilean school to explore how the effects of globally circulating ADHD medications emerge within the localized contexts of everyday users. An analysis of observations of children on ADHD medications within classroom settings is developed which challenges the assumption, pervasive within biomedical paradigms, that the effects of such medications can be understood as resulting directly from their chemical properties and biological modes of action. Our case study highlights the significance of multiple, interacting determinants of drug effects in an everyday setting, focusing in particular on classroom dynamics, teacher–student relations, and the agency of children taking the medications. We conclude that while ADHD medications may act in part by altering physiological processes, an adequate account of their effects requires that analytic attention extends to the sociomaterial contexts in which medications and users are embedded. PMID:28532328

Natural products as modulator of autophagy with potential clinical prospects.

PubMed

Wang, Peiqi; Zhu, Lingjuan; Sun, Dejuan; Gan, Feihong; Gao, Suyu; Yin, Yuanyuan; Chen, Lixia

2017-03-01

Natural compounds derived from living organisms are well defined for their remarkable biological and pharmacological properties likely to be translated into clinical use. Therefore, delving into the mechanisms by which natural compounds protect against diverse diseases may be of great therapeutic benefits for medical practice. Autophagy, an intricate lysosome-dependent digestion process, with implications in a wide variety of pathophysiological settings, has attracted extensive attention over the past few decades. Hitherto, accumulating evidence has revealed that a large number of natural products are involved in autophagy modulation, either inducing or inhibiting autophagy, through multiple signaling pathways and transcriptional regulators. In this review, we summarize natural compounds regulating autophagy in multifarious diseases including cancer, neurodegenerative diseases, cardiovascular diseases, metabolic diseases, and immune diseases, hoping to inspire further investigation of the underlying mechanisms of natural compounds and to facilitate their clinical use for multiple human diseases.

Microscale Symmetrical Electroporator Array as a Versatile Molecular Delivery System

NASA Astrophysics Data System (ADS)

Ouyang, Mengxing; Hill, Winfield; Lee, Jung Hyun; Hur, Soojung Claire

2017-03-01

Successful developments of new therapeutic strategies often rely on the ability to deliver exogenous molecules into cytosol. We have developed a versatile on-chip vortex-assisted electroporation system, engineered to conduct sequential intracellular delivery of multiple molecules into various cell types at low voltage in a dosage-controlled manner. Micro-patterned planar electrodes permit substantial reduction in operational voltages and seamless integration with an existing microfluidic technology. Equipped with real-time process visualization functionality, the system enables on-chip optimization of electroporation parameters for cells with varying properties. Moreover, the system’s dosage control and multi-molecular delivery capabilities facilitate intracellular delivery of various molecules as a single agent or in combination and its utility in biological research has been demonstrated by conducting RNA interference assays. We envision the system to be a powerful tool, aiding a wide range of applications, requiring single-cell level co-administrations of multiple molecules with controlled dosages.

Generation of light-sheet at the end of multimode fibre (Conference Presentation)

NASA Astrophysics Data System (ADS)

Plöschner, Martin; Kollárová, Véra; Dostál, Zbyněk.; Nylk, Jonathan; Barton-Owen, Thomas; Ferrier, David E. K.; Chmelik, Radim; Dholakia, Kishan; Cizmár, TomáÅ.¡

2017-02-01

Light-sheet fluorescence microscopy is quickly becoming one of the cornerstone imaging techniques in biology as it provides rapid, three-dimensional sectioning of specimens at minimal levels of phototoxicity. It is very appealing to bring this unique combination of imaging properties into an endoscopic setting and be able to perform optical sectioning deep in tissues. Current endoscopic approaches for delivery of light-sheet illumination are based on single-mode optical fibre terminated by cylindrical gradient index lens. Such configuration generates a light-sheet plane that is axially fixed and a mechanical movement of either the sample or the endoscope is required to acquire three-dimensional information about the sample. Furthermore, the axial resolution of this technique is limited to 5um. The delivery of the light-sheet through the multimode fibre provides better axial resolution limited only by its numerical aperture, the light-sheet is scanned holographically without any mechanical movement, and multiple advanced light-sheet imaging modalities, such as Bessel and structured illumination Bessel beam, are intrinsically supported by the system due to the cylindrical symmetry of the fibre. We discuss the holographic techniques for generation of multiple light-sheet types and demonstrate the imaging on a sample of fluorescent beads fixed in agarose gel, as well as on a biological sample of Spirobranchus Lamarcki.

Multi-scale Multi-mechanism Toughening of Hydrogels

NASA Astrophysics Data System (ADS)

Zhao, Xuanhe

Hydrogels are widely used as scaffolds for tissue engineering, vehicles for drug delivery, actuators for optics and fluidics, and model extracellular matrices for biological studies. The scope of hydrogel applications, however, is often severely limited by their mechanical properties. Inspired by the mechanics and hierarchical structures of tough biological tissues, we propose that a general principle for the design of tough hydrogels is to implement two mechanisms for dissipating mechanical energy and maintaining high elasticity in hydrogels. A particularly promising strategy for the design is to integrate multiple pairs of mechanisms across multiple length scales into a hydrogel. We develop a multiscale theoretical framework to quantitatively guide the design of tough hydrogels. On the network level, we have developed micro-physical models to characterize the evolution of polymer networks under deformation. On the continuum level, we have implemented constitutive laws formulated from the network-level models into a coupled cohesive-zone and Mullins-effect model to quantitatively predict crack propagation and fracture toughness of hydrogels. Guided by the design principle and quantitative model, we will demonstrate a set of new hydrogels, based on diverse types of polymers, yet can achieve extremely high toughness superior to their natural counterparts such as cartilages. The work was supported by NSF(No. CMMI- 1253495) and ONR (No. N00014-14-1-0528).

Structure-function relations in physiology education: Where's the mechanism?

PubMed

Lira, Matthew E; Gardner, Stephanie M

2017-06-01

Physiology demands systems thinking: reasoning within and between levels of biological organization and across different organ systems. Many physiological mechanisms explain how structures and their properties interact at one level of organization to produce emergent functions at a higher level of organization. Current physiology principles, such as structure-function relations, selectively neglect mechanisms by not mentioning this term explicitly. We explored how students characterized mechanisms and functions to shed light on how students make sense of these terms. Students characterized mechanisms as 1 ) processes that occur at levels of organization lower than that of functions; and 2 ) as detailed events with many steps involved. We also found that students produced more variability in how they characterized functions compared with mechanisms: students characterized functions in relation to multiple levels of organization and multiple definitions. We interpret these results as evidence that students see mechanisms as holding a more narrow definition than used in the biological sciences, and that students struggle to coordinate and distinguish mechanisms from functions due to cognitive processes germane to learning in many domains. We offer the instructional suggestion that we scaffold student learning by affording students opportunities to relate and also distinguish between these terms so central to understanding physiology. Copyright © 2017 the American Physiological Society.

Evaluation of Antioxidant Potential of “Maltese Mushroom” (Cynomorium coccineum) by Means of Multiple Chemical and Biological Assays

PubMed Central

Zucca, Paolo; Rosa, Antonella; Tuberoso, Carlo I. G.; Piras, Alessandra; Rinaldi, Andrea C.; Sanjust, Enrico; Dessì, Maria A.; Rescigno, Antonio

2013-01-01

Cynomorium coccineum is an edible, non-photosynthetic plant widespread along the coasts of the Mediterranean Sea. The medicinal properties of Maltese mushroom—one of the oldest vernacular names used to identify this species—have been kept in high regard since ancient times to the present day. We evaluated the antioxidant potential of fresh specimens of C. coccineum picked in Sardinia, Italy. Both aqueous and methanolic extracts were tested by using multiple assay systems (DPPH, FRAP, TEAC, ORAC-PYR). Total phenolics and flavonoids were also determined. Gallic acid and cyanidin 3-O-glucoside were identified as the main constituents and measured. Both extracts showed antioxidant capacities; ORAC-PYR assay gave the highest antioxidant value in both cases. The methanolic extract was further investigated with in vitro biological models of lipid oxidation; it showed a significant activity in preventing cholesterol degradation and exerted protection against Cu2+-mediated degradation of the liposomal unsaturated fatty acids. Results of the present study demonstrate that the extracts of C. coccineum show a significant total antioxidant power and also exert an in vitro protective effect in different bio-assays of oxidative stress. Therefore, Maltese mushroom can be considered a valuable source of antioxidants and phytochemicals useful in the preparation of nutraceuticals and functional foods. PMID:23344249

Discovering perturbation of modular structure in HIV progression by integrating multiple data sources through non-negative matrix factorization.

PubMed

Ray, Sumanta; Maulik, Ujjwal

2016-12-20

Detecting perturbation in modular structure during HIV-1 disease progression is an important step to understand stage specific infection pattern of HIV-1 virus in human cell. In this article, we proposed a novel methodology on integration of multiple biological information to identify such disruption in human gene module during different stages of HIV-1 infection. We integrate three different biological information: gene expression information, protein-protein interaction information and gene ontology information in single gene meta-module, through non negative matrix factorization (NMF). As the identified metamodules inherit those information so, detecting perturbation of these, reflects the changes in expression pattern, in PPI structure and in functional similarity of genes during the infection progression. To integrate modules of different data sources into strong meta-modules, NMF based clustering is utilized here. Perturbation in meta-modular structure is identified by investigating the topological and intramodular properties and putting rank to those meta-modules using a rank aggregation algorithm. We have also analyzed the preservation structure of significant GO terms in which the human proteins of the meta-modules participate. Moreover, we have performed an analysis to show the change of coregulation pattern of identified transcription factors (TFs) over the HIV progression stages.

Fast wavefront optimization for focusing through biological tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Blochet, Baptiste; Bourdieu, Laurent; Gigan, Sylvain

2017-02-01

The propagation of light in biological tissues is rapidly dominated by multiple scattering: ballistic light is exponentially attenuated, which limits the penetration depth of conventional microscopy techniques. For coherent light, the recombination of the different scattered paths creates a complex interference: speckle. Recently, different wavefront shaping techniques have been developed to coherently manipulate the speckle. It opens the possibility to focus light through complex media and ultimately to image in them, provided however that the medium can be considered as stationary. We have studied the possibility to focus in and through time-varying biological tissues. Their intrinsic temporal dynamics creates a fast decorrelation of the speckle pattern. Therefore, focusing through biological tissues requires fast wavefront shaping devices, sensors and algorithms. We have investigated the use of a MEMS-based spatial light modulator (SLM) and a fast photodetector, combined with FPGA electronics to implement a closed-loop optimization. Our optimization process is just limited by the temporal dynamics of the SLM (200µs) and the computation time (45µs), thus corresponding to a rate of 4 kHz. To our knowledge, it's the fastest closed loop optimization using phase modulators. We have studied the focusing through colloidal solutions of TiO2 particles in glycerol, allowing tunable temporal stability, and scattering properties similar to biological tissues. We have shown that our set-up fulfills the required characteristics (speed, enhancement) to focus through biological tissues. We are currently investigating the focusing through acute rat brain slices and the memory effect in dynamic scattering media.

Cell purification: a new challenge for biobanks.

PubMed

Almeida, Maria; García-Montero, Andres C; Orfao, Alberto

2014-01-01

Performing '-omics' analyses on heterogeneous biological tissue samples, such as blood or bone marrow, can lead to biased or even erroneous results, particularly when the targeted cells and/or molecules are present at relatively low percentages/amounts. In such cases, whole sample analysis will most probably dilute and mask the features of the cell and/or molecules of interest, and this will negatively impact the results and their interpretation. Therefore, frequently it is critically important to have well-characterized and high-quality purified cell populations for the reliable detection of subtle variations in their specific features, such as gene expression profile, protein expression pattern and metabolic status. Biobanks are technological platforms which aim to provide researchers access to a large number of high-quality biological samples and their associated data, particularly to support high-quality scientific and clinical research projects, and such projects will benefit enormously by having access to high-quality purified cell populations or their biological components (e.g. DNA, RNA, proteins). Therefore, a clear opportunity exists for preparative cell sorting techniques in biobanks. Although multiple different cell purification approaches exist or are under development (e.g. cell purification techniques based on cell adherence, density and/or cell size properties, methods based on antibody binding as well as new lab-on-a-chip purification techniques), the choice for a specific technology depends on multiple variables, including cell recovery, purity and yield, among others. In addition, most cell purification approaches are not well suited for high-throughput (HT) purification of multiple cell populations coexisting in a sample. Here we review the most (currently) used cell sorting methods that may be applied for sample preparation in biobanks. For the different approaches, technical considerations about their advantages and limitations are highlighted, and the requirements to be met by a HT cell sorting technology to be used in biobanks are also discussed.

Meta-analysis methods for combining multiple expression profiles: comparisons, statistical characterization and an application guideline

PubMed Central

2013-01-01

Background As high-throughput genomic technologies become accurate and affordable, an increasing number of data sets have been accumulated in the public domain and genomic information integration and meta-analysis have become routine in biomedical research. In this paper, we focus on microarray meta-analysis, where multiple microarray studies with relevant biological hypotheses are combined in order to improve candidate marker detection. Many methods have been developed and applied in the literature, but their performance and properties have only been minimally investigated. There is currently no clear conclusion or guideline as to the proper choice of a meta-analysis method given an application; the decision essentially requires both statistical and biological considerations. Results We performed 12 microarray meta-analysis methods for combining multiple simulated expression profiles, and such methods can be categorized for different hypothesis setting purposes: (1) HS A : DE genes with non-zero effect sizes in all studies, (2) HS B : DE genes with non-zero effect sizes in one or more studies and (3) HS r : DE gene with non-zero effect in "majority" of studies. We then performed a comprehensive comparative analysis through six large-scale real applications using four quantitative statistical evaluation criteria: detection capability, biological association, stability and robustness. We elucidated hypothesis settings behind the methods and further apply multi-dimensional scaling (MDS) and an entropy measure to characterize the meta-analysis methods and data structure, respectively. Conclusions The aggregated results from the simulation study categorized the 12 methods into three hypothesis settings (HS A , HS B , and HS r ). Evaluation in real data and results from MDS and entropy analyses provided an insightful and practical guideline to the choice of the most suitable method in a given application. All source files for simulation and real data are available on the author’s publication website. PMID:24359104

Meta-analysis methods for combining multiple expression profiles: comparisons, statistical characterization and an application guideline.

PubMed

Chang, Lun-Ching; Lin, Hui-Min; Sibille, Etienne; Tseng, George C

2013-12-21

As high-throughput genomic technologies become accurate and affordable, an increasing number of data sets have been accumulated in the public domain and genomic information integration and meta-analysis have become routine in biomedical research. In this paper, we focus on microarray meta-analysis, where multiple microarray studies with relevant biological hypotheses are combined in order to improve candidate marker detection. Many methods have been developed and applied in the literature, but their performance and properties have only been minimally investigated. There is currently no clear conclusion or guideline as to the proper choice of a meta-analysis method given an application; the decision essentially requires both statistical and biological considerations. We performed 12 microarray meta-analysis methods for combining multiple simulated expression profiles, and such methods can be categorized for different hypothesis setting purposes: (1) HS(A): DE genes with non-zero effect sizes in all studies, (2) HS(B): DE genes with non-zero effect sizes in one or more studies and (3) HS(r): DE gene with non-zero effect in "majority" of studies. We then performed a comprehensive comparative analysis through six large-scale real applications using four quantitative statistical evaluation criteria: detection capability, biological association, stability and robustness. We elucidated hypothesis settings behind the methods and further apply multi-dimensional scaling (MDS) and an entropy measure to characterize the meta-analysis methods and data structure, respectively. The aggregated results from the simulation study categorized the 12 methods into three hypothesis settings (HS(A), HS(B), and HS(r)). Evaluation in real data and results from MDS and entropy analyses provided an insightful and practical guideline to the choice of the most suitable method in a given application. All source files for simulation and real data are available on the author's publication website.

Enhanced in Vivo Efficacy of a Type I Interferon Superagonist with Extended Plasma Half-life in a Mouse Model of Multiple Sclerosis*

PubMed Central

Harari, Daniel; Kuhn, Nadine; Abramovich, Renne; Sasson, Keren; Zozulya, Alla L.; Smith, Paul; Schlapschy, Martin; Aharoni, Rina; Köster, Mario; Eilam, Raya; Skerra, Arne; Schreiber, Gideon

2014-01-01

IFNβ is a common therapeutic option to treat multiple sclerosis. It is unique among the family of type I IFNs in that it binds to the interferon receptors with high affinity, conferring exceptional biological properties. We have previously reported the generation of an interferon superagonist (dubbed YNSα8) that is built on the backbone of a low affinity IFNα but modified to exhibit higher receptor affinity than even for IFNβ. Here, YNSα8 was fused with a 600-residue hydrophilic, unstructured N-terminal polypeptide chain comprising proline, alanine, and serine (PAS) to prolong its plasma half-life via “PASylation.” PAS-YNSα8 exhibited a 10-fold increased half-life in both pharmacodynamic and pharmacokinetic assays in a transgenic mouse model harboring the human receptors, notably without any detectable loss in biological potency or bioavailability. This long-lived superagonist conferred significantly improved protection from MOG35–55-induced experimental autoimmune encephalomyelitis compared with IFNβ, despite being injected with a 4-fold less frequency and at an overall 16-fold lower dosage. These data were corroborated by FACS measurements showing a decrease of CD11b+/CD45hi myeloid lineage cells detectable in the CNS, as well as a decrease in IBA+ cells in spinal cord sections determined by immunohistochemistry for PAS-YNSα8-treated animals. Importantly, PAS-YNSα8 did not induce antibodies upon repeated administration, and its biological efficacy remained unchanged after 21 days of treatment. A striking correlation between increased levels of CD274 (PD-L1) transcripts from spleen-derived CD4+ cells and improved clinical response to autoimmune encephalomyelitis was observed, indicating that, at least in this mouse model of multiple sclerosis, CD274 may serve as a biomarker to predict the effectiveness of IFN therapy to treat this complex disease. PMID:25193661

Weighted Statistical Binning: Enabling Statistically Consistent Genome-Scale Phylogenetic Analyses

PubMed Central

Bayzid, Md Shamsuzzoha; Mirarab, Siavash; Boussau, Bastien; Warnow, Tandy

2015-01-01

Because biological processes can result in different loci having different evolutionary histories, species tree estimation requires multiple loci from across multiple genomes. While many processes can result in discord between gene trees and species trees, incomplete lineage sorting (ILS), modeled by the multi-species coalescent, is considered to be a dominant cause for gene tree heterogeneity. Coalescent-based methods have been developed to estimate species trees, many of which operate by combining estimated gene trees, and so are called "summary methods". Because summary methods are generally fast (and much faster than more complicated coalescent-based methods that co-estimate gene trees and species trees), they have become very popular techniques for estimating species trees from multiple loci. However, recent studies have established that summary methods can have reduced accuracy in the presence of gene tree estimation error, and also that many biological datasets have substantial gene tree estimation error, so that summary methods may not be highly accurate in biologically realistic conditions. Mirarab et al. (Science 2014) presented the "statistical binning" technique to improve gene tree estimation in multi-locus analyses, and showed that it improved the accuracy of MP-EST, one of the most popular coalescent-based summary methods. Statistical binning, which uses a simple heuristic to evaluate "combinability" and then uses the larger sets of genes to re-calculate gene trees, has good empirical performance, but using statistical binning within a phylogenomic pipeline does not have the desirable property of being statistically consistent. We show that weighting the re-calculated gene trees by the bin sizes makes statistical binning statistically consistent under the multispecies coalescent, and maintains the good empirical performance. Thus, "weighted statistical binning" enables highly accurate genome-scale species tree estimation, and is also statistically consistent under the multi-species coalescent model. New data used in this study are available at DOI: http://dx.doi.org/10.6084/m9.figshare.1411146, and the software is available at https://github.com/smirarab/binning. PMID:26086579

DLocalMotif: a discriminative approach for discovering local motifs in protein sequences.

PubMed

Mehdi, Ahmed M; Sehgal, Muhammad Shoaib B; Kobe, Bostjan; Bailey, Timothy L; Bodén, Mikael

2013-01-01

Local motifs are patterns of DNA or protein sequences that occur within a sequence interval relative to a biologically defined anchor or landmark. Current protein motif discovery methods do not adequately consider such constraints to identify biologically significant motifs that are only weakly over-represented but spatially confined. Using negatives, i.e. sequences known to not contain a local motif, can further increase the specificity of their discovery. This article introduces the method DLocalMotif that makes use of positional information and negative data for local motif discovery in protein sequences. DLocalMotif combines three scoring functions, measuring degrees of motif over-representation, entropy and spatial confinement, specifically designed to discriminatively exploit the availability of negative data. The method is shown to outperform current methods that use only a subset of these motif characteristics. We apply the method to several biological datasets. The analysis of peroxisomal targeting signals uncovers several novel motifs that occur immediately upstream of the dominant peroxisomal targeting signal-1 signal. The analysis of proline-tyrosine nuclear localization signals uncovers multiple novel motifs that overlap with C2H2 zinc finger domains. We also evaluate the method on classical nuclear localization signals and endoplasmic reticulum retention signals and find that DLocalMotif successfully recovers biologically relevant sequence properties. http://bioinf.scmb.uq.edu.au/dlocalmotif/

Mammalian designer cells: Engineering principles and biomedical applications.

PubMed

Xie, Mingqi; Fussenegger, Martin

2015-07-01

Biotechnology is a widely interdisciplinary field focusing on the use of living cells or organisms to solve established problems in medicine, food production and agriculture. Synthetic biology, the science of engineering complex biological systems that do not exist in nature, continues to provide the biotechnology industry with tools, technologies and intellectual property leading to improved cellular performance. One key aspect of synthetic biology is the engineering of deliberately reprogrammed designer cells whose behavior can be controlled over time and space. This review discusses the most commonly used techniques to engineer mammalian designer cells; while control elements acting on the transcriptional and translational levels of target gene expression determine the kinetic and dynamic profiles, coupling them to a variety of extracellular stimuli permits their remote control with user-defined trigger signals. Designer mammalian cells with novel or improved biological functions not only directly improve the production efficiency during biopharmaceutical manufacturing but also open the door for cell-based treatment strategies in molecular and translational medicine. In the future, the rational combination of multiple sets of designer cells could permit the construction and regulation of higher-order systems with increased complexity, thereby enabling the molecular reprogramming of tissues, organisms or even populations with highest precision. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Calcium as a signal integrator in developing epithelial tissues.

PubMed

Brodskiy, Pavel A; Zartman, Jeremiah J

2018-05-16

Decoding how tissue properties emerge across multiple spatial and temporal scales from the integration of local signals is a grand challenge in quantitative biology. For example, the collective behavior of epithelial cells is critical for shaping developing embryos. Understanding how epithelial cells interpret a diverse range of local signals to coordinate tissue-level processes requires a systems-level understanding of development. Integration of multiple signaling pathways that specify cell signaling information requires second messengers such as calcium ions. Increasingly, specific roles have been uncovered for calcium signaling throughout development. Calcium signaling regulates many processes including division, migration, death, and differentiation. However, the pleiotropic and ubiquitous nature of calcium signaling implies that many additional functions remain to be discovered. Here we review a selection of recent studies to highlight important insights into how multiple signals are transduced by calcium transients in developing epithelial tissues. Quantitative imaging and computational modeling have provided important insights into how calcium signaling integration occurs. Reverse-engineering the conserved features of signal integration mediated by calcium signaling will enable novel approaches in regenerative medicine and synthetic control of morphogenesis.

Multienzyme kinetics and sequential metabolism.

PubMed

Wienkers, Larry C; Rock, Brooke

2014-01-01

Enzymes are the catalysts of biological systems and are extremely efficient. A typical enzyme accelerates the rate of a reaction by factors of at least a million compared to the rate of the same reaction in the absence of the enzyme. In contrast to traditional catalytic enzymes, the family of cytochrome P450 (CYP) enzymes are catalytically promiscuous, and thus they possess remarkable versatility in substrates. The great diversity of reactions catalyzed by CYP enzymes appears to be based on two unique properties of these heme proteins, the ability of their iron to exist under multiple oxidation states with different reactivities and a flexible active site that can accommodate a wide variety of substrates. Herein is a discussion of two distinct types of kinetics observed with CYP enzymes. The first example is of CYP complex kinetic profiles when multiple CYP enzymes form the sample product. The second is sequential metabolism, in other words, the formation of multiple products from one CYP enzyme. Given the degree of CYP enzyme promiscuity, it is hardly surprising that there is also a high degree of complex kinetic profiles generated during the catalytic cycle.

Development and applications of transgenesis in the yellow fever mosquito, Aedes aegypti.

PubMed

Adelman, Zachary N; Jasinskiene, Nijole; James, Anthony A

2002-04-30

Transgenesis technology has been developed for the yellow fever mosquito, Aedes aegypti. Successful integration of exogenous DNA into the germline of this mosquito has been achieved with the class II transposable elements, Hermes, mariner and piggyBac. A number of marker genes, including the cinnabar(+) gene of Drosophila melanogaster, and fluorescent protein genes, can be used to monitor the insertion of these elements. The availability of multiple elements and marker genes provides a powerful set of tools to investigate basic biological properties of this vector insect, as well as the materials for developing novel, genetics-based, control strategies for the transmission of disease.

The recent progress of isoxazole in medicinal chemistry.

PubMed

Zhu, Jie; Mo, Jun; Lin, Hong-Zhi; Chen, Yao; Sun, Hao-Peng

2018-05-28

Isoxazole compounds exhibit a wide spectrum of targets and broad biological activities. Developing compounds with heterocycle rings has been one of the trends. The integration of isoxazole ring can offer improved physical-chemical properties. Because of the unique profiles, isoxazole ring becomes a popular moiety in compounds design. In this review article, the major focus has been paid to the applications of isoxazole compounds in treating multiple diseases, including anticancer, antimicrobial, anti-inflammatory, etc. Strategies for compounds design for preclinical, clinical, and FDA approved drugs were discussed. Also, the emphasis has been addressed to the future perspectives and trend for the application. Copyright © 2018 Elsevier Ltd. All rights reserved.

Multinuclear metal-binding ability of a carotene

PubMed Central

Horiuchi, Shinnosuke; Tachibana, Yuki; Yamashita, Mitsuki; Yamamoto, Koji; Masai, Kohei; Takase, Kohei; Matsutani, Teruo; Kawamata, Shiori; Kurashige, Yuki; Yanai, Takeshi; Murahashi, Tetsuro

2015-01-01

Carotenes are naturally abundant unsaturated hydrocarbon pigments, and their fascinating physical and chemical properties have been studied intensively not only for better understanding of the roles in biological processes but also for the use in artificial chemical systems. However, their metal-binding ability has been virtually unexplored. Here we report that β-carotene has the ability to assemble and align ten metal atoms to afford decanuclear homo- and heterometal chain complexes. The metallo–carotenoid framework shows reversible metalation–demetalation reactivity with multiple metals, which allows us to control the size of metal chains as well as the heterobimetallic composition and arrangement of the carotene-supported metal chains. PMID:25857402

Protein hydrogen exchange at residue resolution by proteolytic fragmentation mass spectrometry analysis

PubMed Central

Kan, Zhong-Yuan; Walters, Benjamin T.; Mayne, Leland; Englander, S. Walter

2013-01-01

Hydrogen exchange technology provides a uniquely powerful instrument for measuring protein structural and biophysical properties, quantitatively and in a nonperturbing way, and determining how these properties are implemented to produce protein function. A developing hydrogen exchange–mass spectrometry method (HX MS) is able to analyze large biologically important protein systems while requiring only minuscule amounts of experimental material. The major remaining deficiency of the HX MS method is the inability to deconvolve HX results to individual amino acid residue resolution. To pursue this goal we used an iterative optimization program (HDsite) that integrates recent progress in multiple peptide acquisition together with previously unexamined isotopic envelope-shape information and a site-resolved back-exchange correction. To test this approach, residue-resolved HX rates computed from HX MS data were compared with extensive HX NMR measurements, and analogous comparisons were made in simulation trials. These tests found excellent agreement and revealed the important computational determinants. PMID:24019478

Electrospray ionization mass spectrometry: a technique to access the information beyond the molecular weight of the analyte.

PubMed

Banerjee, Shibdas; Mazumdar, Shyamalava

2012-01-01

The Electrospray Ionization (ESI) is a soft ionization technique extensively used for production of gas phase ions (without fragmentation) of thermally labile large supramolecules. In the present review we have described the development of Electrospray Ionization mass spectrometry (ESI-MS) during the last 25 years in the study of various properties of different types of biological molecules. There have been extensive studies on the mechanism of formation of charged gaseous species by the ESI. Several groups have investigated the origin and implications of the multiple charge states of proteins observed in the ESI-mass spectra of the proteins. The charged analytes produced by ESI can be fragmented by activating them in the gas-phase, and thus tandem mass spectrometry has been developed, which provides very important insights on the structural properties of the molecule. The review will highlight recent developments and emerging directions in this fascinating area of research.

Surface proton transport of fully protonated poly(aspartic acid) thin films on quartz substrates

NASA Astrophysics Data System (ADS)

Nagao, Yuki; Kubo, Takahiro

2014-12-01

Thin film structure and the proton transport property of fully protonated poly(aspartic acid) (P-Asp100) have been investigated. An earlier study assessed partially protonated poly(aspartic acid), highly oriented thin film structure and enhancement of the internal proton transport. In this study of P-Asp100, IR p-polarized multiple-angle incidence resolution (P-MAIR) spectra were measured to investigate the thin film structure. The obtained thin films, with thicknesses of 120-670 nm, had no oriented structure. Relative humidity dependence of the resistance, proton conductivity, and normalized resistance were examined to ascertain the proton transport property of P-Asp100 thin films. The obtained data showed that the proton transport of P-Asp100 thin films might occur on the surface, not inside of the thin film. This phenomenon might be related with the proton transport of the biological system.

Real-time absorption and scattering characterization of slab-shaped turbid samples obtained by a combination of angular and spatially resolved measurements.

PubMed

Dam, Jan S; Yavari, Nazila; Sørensen, Søren; Andersson-Engels, Stefan

2005-07-10

We present a fast and accurate method for real-time determination of the absorption coefficient, the scattering coefficient, and the anisotropy factor of thin turbid samples by using simple continuous-wave noncoherent light sources. The three optical properties are extracted from recordings of angularly resolved transmittance in addition to spatially resolved diffuse reflectance and transmittance. The applied multivariate calibration and prediction techniques are based on multiple polynomial regression in combination with a Newton--Raphson algorithm. The numerical test results based on Monte Carlo simulations showed mean prediction errors of approximately 0.5% for all three optical properties within ranges typical for biological media. Preliminary experimental results are also presented yielding errors of approximately 5%. Thus the presented methods show a substantial potential for simultaneous absorption and scattering characterization of turbid media.

High-value components and bioactives from sea cucumbers for functional foods--a review.

PubMed

Bordbar, Sara; Anwar, Farooq; Saari, Nazamid

2011-01-01

Sea cucumbers, belonging to the class Holothuroidea, are marine invertebrates, habitually found in the benthic areas and deep seas across the world. They have high commercial value coupled with increasing global production and trade. Sea cucumbers, informally named as bêche-de-mer, or gamat, have long been used for food and folk medicine in the communities of Asia and Middle East. Nutritionally, sea cucumbers have an impressive profile of valuable nutrients such as Vitamin A, Vitamin B1 (thiamine), Vitamin B2 (riboflavin), Vitamin B3 (niacin), and minerals, especially calcium, magnesium, iron and zinc. A number of unique biological and pharmacological activities including anti-angiogenic, anticancer, anticoagulant, anti-hypertension, anti-inflammatory, antimicrobial, antioxidant, antithrombotic, antitumor and wound healing have been ascribed to various species of sea cucumbers. Therapeutic properties and medicinal benefits of sea cucumbers can be linked to the presence of a wide array of bioactives especially triterpene glycosides (saponins), chondroitin sulfates, glycosaminoglycan (GAGs), sulfated polysaccharides, sterols (glycosides and sulfates), phenolics, cerberosides, lectins, peptides, glycoprotein, glycosphingolipids and essential fatty acids. This review is mainly designed to cover the high-value components and bioactives as well as the multiple biological and therapeutic properties of sea cucumbers with regard to exploring their potential uses for functional foods and nutraceuticals.

Effects of Ocean Ecosystem on Marine Aerosol-Cloud Interaction

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

Meskhidze, Nicholas; Nenes, Athanasios

Using smore » atellite data for the surface ocean, aerosol optical depth (AOD), and cloud microphysical parameters, we show that statistically significant positive correlations exist between ocean ecosystem productivity, the abundance of submicron aerosols, and cloud microphysical properties over different parts of the remote oceans. The correlation coefficient for remotely sensed surface chlorophyll a concentration ([Chl- a ]) and liquid cloud effective radii over productive areas of the oceans varies between − 0.2 and − 0.6 . Special attention is given to identifying (and addressing) problems from correlation analysis used in the previous studies that can lead to erroneous conclusions. A new approach (using the difference between retrieved AOD and predicted sea salt aerosol optical depth, AOD diff ) is developed to explore causal links between ocean physical and biological systems and the abundance of cloud condensation nuclei (CCN) in the remote marine atmosphere. We have found that over multiple time periods, 550 nm AOD diff (sensitive to accumulation mode aerosol, which is the prime contributor to CCN) correlates well with [Chl- a ] over the productive waters of the Southern Ocean. Since [Chl- a ] can be used as a proxy of ocean biological productivity, our analysis demonstrates the role of ocean ecology in contributing CCN, thus shaping the microphysical properties of low-level marine clouds.« less

High-Value Components and Bioactives from Sea Cucumbers for Functional Foods—A Review

PubMed Central

Bordbar, Sara; Anwar, Farooq; Saari, Nazamid

2011-01-01

Sea cucumbers, belonging to the class Holothuroidea, are marine invertebrates, habitually found in the benthic areas and deep seas across the world. They have high commercial value coupled with increasing global production and trade. Sea cucumbers, informally named as bêche-de-mer, or gamat, have long been used for food and folk medicine in the communities of Asia and Middle East. Nutritionally, sea cucumbers have an impressive profile of valuable nutrients such as Vitamin A, Vitamin B1 (thiamine), Vitamin B2 (riboflavin), Vitamin B3 (niacin), and minerals, especially calcium, magnesium, iron and zinc. A number of unique biological and pharmacological activities including anti-angiogenic, anticancer, anticoagulant, anti-hypertension, anti-inflammatory, antimicrobial, antioxidant, antithrombotic, antitumor and wound healing have been ascribed to various species of sea cucumbers. Therapeutic properties and medicinal benefits of sea cucumbers can be linked to the presence of a wide array of bioactives especially triterpene glycosides (saponins), chondroitin sulfates, glycosaminoglycan (GAGs), sulfated polysaccharides, sterols (glycosides and sulfates), phenolics, cerberosides, lectins, peptides, glycoprotein, glycosphingolipids and essential fatty acids. This review is mainly designed to cover the high-value components and bioactives as well as the multiple biological and therapeutic properties of sea cucumbers with regard to exploring their potential uses for functional foods and nutraceuticals. PMID:22072996

Nasal-nanotechnology: revolution for efficient therapeutics delivery.

PubMed

Kumar, Amrish; Pandey, Aditya Nath; Jain, Sunil Kumar

2016-01-01

In recent years, nanotechnology-based delivery systems have gained interest to overcome the problems of restricted absorption of therapeutic agents from the nasal cavity, depending upon the physicochemical properties of the drug and physiological properties of the human nose. The well-tolerated and non-invasive nasal drug delivery when combined with the nanotechnology-based novel formulations and carriers, opens the way for the effective systemic and brain targeting delivery of various therapeutic agents. To accomplish competent drug delivery, it is imperative to recognize the interactions among the nanomaterials and the nasal biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signaling involved in patho-biology of the disease under consideration. Quite a few systems have been successfully formulated using nanomaterials for intranasal (IN) delivery. Carbon nanotubes (CNTs), chitosan, polylactic-co-glycolic acid (PLGA) and PLGA-based nanosystems have also been studied in vitro and in vivo for the delivery of several therapeutic agents which shown promising concentrations in the brain after nasal administration. The use of nanomaterials including peptide-based nanotubes and nanogels (NGs) for vaccine delivery via nasal route is a new approach to control the disease progression. In this review, the recent developments in nanotechnology utilized for nasal drug delivery have been discussed.

Local administration of curcumin-loaded nanoparticles effectively inhibits inflammation and bone resorption associated with experimental periodontal disease.

PubMed

Zambrano, Laura M G; Brandao, Dayane A; Rocha, Fernanda R G; Marsiglio, Raquel P; Longo, Ieda B; Primo, Fernando L; Tedesco, Antonio C; Guimaraes-Stabili, Morgana R; Rossa Junior, Carlos

2018-04-27

There is evidence indicating that curcumin has multiple biological activities, including anti-inflammatory properties. In vitro and in vivo studies demonstrate that curcumin may attenuate inflammation and the connective tissue destruction associated with periodontal disease. Most of these studies use systemic administration, and considering the site-specific nature of periodontal disease and also the poor pharmacodynamic properties of curcumin, we conducted this proof of principle study to assess the biological effect of the local administration of curcumin in a nanoparticle vehicle on experimental periodontal disease. We used 16 rats divided into two groups of 8 animals according to the induction of experimental periodontal disease by bilateral injections of LPS or of the vehicle control directly into the gingival tissues 3×/week for 4 weeks. The same volume of curcumin-loaded nanoparticles or of nanoparticle vehicle was injected into the same sites 2×/week. µCT analysis showed that local administration of curcumin resulted in a complete inhibition of inflammatory bone resorption and in a significant decrease of both osteoclast counts and of the inflammatory infiltrate; as well as a marked attenuation of p38 MAPK and NF-kB activation. We conclude that local administration of curcumin-loaded nanoparticles effectively inhibited inflammation and bone resorption associated with experimental periodontal disease.

Use of Natural Products as Chemical Library for Drug Discovery and Network Pharmacology

PubMed Central

Gu, Jiangyong; Gui, Yuanshen; Chen, Lirong; Yuan, Gu; Lu, Hui-Zhe; Xu, Xiaojie

2013-01-01

Background Natural products have been an important source of lead compounds for drug discovery. How to find and evaluate bioactive natural products is critical to the achievement of drug/lead discovery from natural products. Methodology We collected 19,7201 natural products structures, reported biological activities and virtual screening results. Principal component analysis was employed to explore the chemical space, and we found that there was a large portion of overlap between natural products and FDA-approved drugs in the chemical space, which indicated that natural products had large quantity of potential lead compounds. We also explored the network properties of natural product-target networks and found that polypharmacology was greatly enriched to those compounds with large degree and high betweenness centrality. In order to make up for a lack of experimental data, high throughput virtual screening was employed. All natural products were docked to 332 target proteins of FDA-approved drugs. The most potential natural products for drug discovery and their indications were predicted based on a docking score-weighted prediction model. Conclusions Analysis of molecular descriptors, distribution in chemical space and biological activities of natural products was conducted in this article. Natural products have vast chemical diversity, good drug-like properties and can interact with multiple cellular target proteins. PMID:23638153

Effects of Ocean Ecosystem on Marine Aerosol-Cloud Interaction

DOE PAGES

Meskhidze, Nicholas; Nenes, Athanasios

2010-01-01

Using smore » atellite data for the surface ocean, aerosol optical depth (AOD), and cloud microphysical parameters, we show that statistically significant positive correlations exist between ocean ecosystem productivity, the abundance of submicron aerosols, and cloud microphysical properties over different parts of the remote oceans. The correlation coefficient for remotely sensed surface chlorophyll a concentration ([Chl- a ]) and liquid cloud effective radii over productive areas of the oceans varies between − 0.2 and − 0.6 . Special attention is given to identifying (and addressing) problems from correlation analysis used in the previous studies that can lead to erroneous conclusions. A new approach (using the difference between retrieved AOD and predicted sea salt aerosol optical depth, AOD diff ) is developed to explore causal links between ocean physical and biological systems and the abundance of cloud condensation nuclei (CCN) in the remote marine atmosphere. We have found that over multiple time periods, 550 nm AOD diff (sensitive to accumulation mode aerosol, which is the prime contributor to CCN) correlates well with [Chl- a ] over the productive waters of the Southern Ocean. Since [Chl- a ] can be used as a proxy of ocean biological productivity, our analysis demonstrates the role of ocean ecology in contributing CCN, thus shaping the microphysical properties of low-level marine clouds.« less

AIM for Allostery: Using the Ising Model to Understand Information Processing and Transmission in Allosteric Biomolecular Systems.

PubMed

LeVine, Michael V; Weinstein, Harel

2015-05-01

In performing their biological functions, molecular machines must process and transmit information with high fidelity. Information transmission requires dynamic coupling between the conformations of discrete structural components within the protein positioned far from one another on the molecular scale. This type of biomolecular "action at a distance" is termed allostery . Although allostery is ubiquitous in biological regulation and signal transduction, its treatment in theoretical models has mostly eschewed quantitative descriptions involving the system's underlying structural components and their interactions. Here, we show how Ising models can be used to formulate an approach to allostery in a structural context of interactions between the constitutive components by building simple allosteric constructs we termed Allosteric Ising Models (AIMs). We introduce the use of AIMs in analytical and numerical calculations that relate thermodynamic descriptions of allostery to the structural context, and then show that many fundamental properties of allostery, such as the multiplicative property of parallel allosteric channels, are revealed from the analysis of such models. The power of exploring mechanistic structural models of allosteric function in more complex systems by using AIMs is demonstrated by building a model of allosteric signaling for an experimentally well-characterized asymmetric homodimer of the dopamine D2 receptor.

Acquisition of Cooperative Small Unmanned Aerial Systems for Advancing Man Machine Interface Research

DTIC Science & Technology

2016-08-24

global sensor field of views (FOVs), mimicking biological systems such as an insect fly eye , but allowing multiple aperture configurations. Due to...synthetic, global sensor field of views (FOVs), mimicking biological systems such as an insect fly eye , but allowing multiple aperture configurations. Due to...such as an insect fly eye , but allowing multiple aperture configurations. Due to the desired nature of distributed networked aerial vehicles (for the

Multisensor Instrument for Real-Time Biological Monitoring

NASA Technical Reports Server (NTRS)

Zhang, Sean (Zhanxiang); Xu, Guoda; Qiu, Wei; Lin, Freddie

2004-01-01

The figure schematically depicts an instrumentation system, called a fiber optic-based integration system (FOBIS), that is undergoing development to enable real-time monitoring of fluid cell cultures, bioprocess flows, and the like. The FOBIS design combines a micro flow cytometer (MFC), a microphotometer (MP), and a fluorescence-spectrum- or binding-force-measuring micro-sensor (MS) in a single instrument that is capable of measuring multiple biological parameters simultaneously or sequentially. The fiber-optic-based integration system is so named because the MFC, the MP, and the MS are integrated into a single optical system that is coupled to light sources and photometric equipment via optical fibers. The optical coupling components also include a wavelength-division multiplexer and diffractive optical elements. The FOBIS includes a laserdiode- and fiber-optic-based optical trapping subsystem (optical tweezers ) with microphotometric and micro-sensing capabilities for noninvasive confinement and optical measurement of relevant parameters of a single cell or other particle. Some of the measurement techniques implemented together by the FOBIS have long been used separately to obtain basic understanding of the optical properties of individual cells and other organisms, the optical properties of populations of organisms, and the interrelationships among these properties, physiology of the organisms, and physical processes that govern the media that surround the organisms. For example, flow cytometry yields information on numerical concentrations, cross-sectional areas, and types of cells or other particles. Micro-sensing can be used to measure pH and concentrations of oxygen, carbon dioxide, glucose, metabolites, calcium, and antigens in a cell-culture fluid, thereby providing feedback that can be helpful in improving control over a bioprocess. Microphotometry (including measurements of scattering and fluorescence) can yield further information about optically trapped individual particles. In addition to the multifunctionality not previously available in a single biological monitoring system, the FOBIS offers advantages of low mass, sensitivity, accuracy, portability, low cost, compactness (the overall dimensions of the fully developed FOBIS sensor head are expected to be less than 1 by 1 by 2 cm), and immunity to electromagnetic interference at suboptical frequencies. FOBIS could be useful in a variety of laboratory and field settings in such diverse endeavors as medical, veterinary, and general biological research; medical and veterinary diagnosis monitoring of industrial bioprocesses; and analysis of biological contaminants in air, water, and food.

Inverse Algorithm Optimization for Determining Optical Properties of Biological Materials from Spatially-Resolved Diffuse Reflectance

USDA-ARS?s Scientific Manuscript database

Optical characterization of biological materials is useful in many scientific and industrial applications like biomedical diagnosis and nondestructive quality evaluation of food and agricultural products. However, accurate determination of the optical properties from intact biological materials base...

Integrated Analysis of Pharmacologic, Clinical, and SNP Microarray Data using Projection onto the Most Interesting Statistical Evidence with Adaptive Permutation Testing

PubMed Central

Pounds, Stan; Cao, Xueyuan; Cheng, Cheng; Yang, Jun; Campana, Dario; Evans, William E.; Pui, Ching-Hon; Relling, Mary V.

2010-01-01

Powerful methods for integrated analysis of multiple biological data sets are needed to maximize interpretation capacity and acquire meaningful knowledge. We recently developed Projection Onto the Most Interesting Statistical Evidence (PROMISE). PROMISE is a statistical procedure that incorporates prior knowledge about the biological relationships among endpoint variables into an integrated analysis of microarray gene expression data with multiple biological and clinical endpoints. Here, PROMISE is adapted to the integrated analysis of pharmacologic, clinical, and genome-wide genotype data that incorporating knowledge about the biological relationships among pharmacologic and clinical response data. An efficient permutation-testing algorithm is introduced so that statistical calculations are computationally feasible in this higher-dimension setting. The new method is applied to a pediatric leukemia data set. The results clearly indicate that PROMISE is a powerful statistical tool for identifying genomic features that exhibit a biologically meaningful pattern of association with multiple endpoint variables. PMID:21516175

[Study of biological performance of Chinese materia medica with either a cold or hot property based on the three-element mathematical analysis model].

PubMed

Jin, Rui; Zhang, Bing; Liu, Xiao-Qing; Liu, Sen-Mao; Liu, Xin; Li, Lian-Zhen; Zhang, Qian; Xue, Chun-Miao

2011-07-01

The properties of Chinese materia medica are believed to be the summarization of the effects of biological performance on the various body states. Systemic discussion of chemical-factor elements, body-condition elements, biological-performance elements and their interrelationships is needed for research into the properties of Chinese materia medica. Following the practical characteristics of Chinese medicine, the three-element mathematical model was formed by introducing some mathematical concepts and methods and was used to study the cold or hot property of Chinese medicine, and to investigate the difference in biological performances of the two properties. By using the concept of different functionality of Chinese medicine on abnormal states and the idea of interaction in mathematics, the effects of chemical-factor elements and body-condition elements were normalized to the amount of biological performance which was represented by some important indicators. The three-element mathematical model was formed with scatter plots through four steps, including effect separation, intensity calculation, frequency statistics and relevance analysis. A comparison pharmacology experiment of administration of hot property medicines, Fuzi (Radix Aconiti Lateralis Preparata) and Rougui (Cortex Cinnamomi), and cold property medicines, Huangbai (Cortex Phellodendri) and Zhizi (Fructus Gardeniae) on normal and glucocorticoid-induced yang-deficiency and yin-deficiency states was designed. The results were analyzed by the mathematical model. The scatter plots were the main output of model analysis. The expression of cold property and hot property was able to be quantified by frequency distribution of biological indexes of administrations on yang-deficiency and yin-deficiency states in the "efficacy zone" and "toxicity zone" of the plots and by the relevance analysis. The ratios of biological indicator frequency in the "efficacy zone" of administrations on yang-deficiency state and yin-deficiency state were 7:3 for Fuzi, 3:3 for Rougui, 4:4 for Huangbai and 1:5 for Zhizi. The sums of the biological indicator frequency in the "toxicity zone" of administration on the two states were 4 for Fuzi, 0 for Rougui, 2 for Huangbai and 4 for Zhizi. The relevance analysis showed that the order from Fuzi, Rougui, Huangbai to Zhizi was proportional to the change from "be true of yang-deficiency state" to "be true of yin-deficiency state". The extent of the hot property decreased while that of the cold property increased in the order of Fuzi, Rougui, Huangbai and Zhizi. The stronger the efficacy of above medicines is, the more obvious the toxicity displayed. The three-element mathematical model employed in this study is effectively capable of explaining the different biological expressions between hot property medicines and cold property medicines. This suggests that it may provide a mathematical tool and theoretical basis for the modern interpretation of cold property and hot property of Chinese medicine, and provide new ideas for further studing into the essence of Chinese medicine property theory.

Circulating exosomes potentiate tumor malignant properties in a mouse model of chronic sleep fragmentation

PubMed Central

Khalyfa, Abdelnaby; Almendros, Isaac; Gileles-Hillel, Alex; Akbarpour, Mahzad; Trzepizur, Wojciech; Mokhlesi, Babak; Huang, Lei; Andrade, Jorge; Farré, Ramon; Gozal, David

2016-01-01

Background Chronic sleep fragmentation (SF) increases cancer aggressiveness in mice. Exosomes exhibit pleiotropic biological functions, including immune regulatory functions, antigen presentation, intracellular communication and inter-cellular transfer of RNA and proteins. We hypothesized that SF-induced alterations in biosynthesis and cargo of plasma exosomes may affect tumor cell properties. Results SF-derived exosomes increased tumor cell proliferation (~13%), migration (~2.3-fold) and extravasation (~10%) when compared to exosomes from SC-exposed mice. Similarly, Pre exosomes from OSA patients significantly enhanced proliferation and migration of human adenocarcinoma cells compared to Post. SF-exosomal cargo revealed 3 discrete differentially expressed miRNAs, and exploration of potential mRNA targets in TC1 tumor cells uncovered 132 differentially expressed genes that encode for multiple cancer-related pathways. Methods Plasma-derived exosomes from C57/B6 mice exposed to 6 wks of SF or sleep control (SC), and from adult human patients with obstructive sleep apnea (OSA) before (Pre) and after adherent treatment for 6 wks (Post) were co-cultured with mouse lung TC1 or human adenocarcinoma tumor cell lines, respectively. Proliferation, migration, invasion, endothelial barrier integrity and extravasation assays of tumor cells were performed. Plasma mouse exosomal miRNAs were profiled with arrays, and transcriptomic assessments of TC1 cells exposed to SF or SC exosomes were conducted to identify gene targets. Conclusions Chronic SF induces alterations in exosomal miRNA cargo that alter the biological properties of TC1 lung tumor cells to enhance their proliferative, migratory and extravasation properties, and similar findings occur in OSA patients, in whom SF is a constitutive component of their sleep disorder. Thus, exosomes could participate, at least in part, in the adverse cancer outcomes observed in OSA. PMID:27419627

A Computational Framework for 3D Mechanical Modeling of Plant Morphogenesis with Cellular Resolution

PubMed Central

Gilles, Benjamin; Hamant, Olivier; Boudaoud, Arezki; Traas, Jan; Godin, Christophe

2015-01-01

The link between genetic regulation and the definition of form and size during morphogenesis remains largely an open question in both plant and animal biology. This is partially due to the complexity of the process, involving extensive molecular networks, multiple feedbacks between different scales of organization and physical forces operating at multiple levels. Here we present a conceptual and modeling framework aimed at generating an integrated understanding of morphogenesis in plants. This framework is based on the biophysical properties of plant cells, which are under high internal turgor pressure, and are prevented from bursting because of the presence of a rigid cell wall. To control cell growth, the underlying molecular networks must interfere locally with the elastic and/or plastic extensibility of this cell wall. We present a model in the form of a three dimensional (3D) virtual tissue, where growth depends on the local modulation of wall mechanical properties and turgor pressure. The model shows how forces generated by turgor-pressure can act both cell autonomously and non-cell autonomously to drive growth in different directions. We use simulations to explore lateral organ formation at the shoot apical meristem. Although different scenarios lead to similar shape changes, they are not equivalent and lead to different, testable predictions regarding the mechanical and geometrical properties of the growing lateral organs. Using flower development as an example, we further show how a limited number of gene activities can explain the complex shape changes that accompany organ outgrowth. PMID:25569615

Endowing carbon nanotubes with biological and biomedical properties by chemical modifications.

PubMed

Battigelli, Alessia; Ménard-Moyon, Cécilia; Da Ros, Tatiana; Prato, Maurizio; Bianco, Alberto

2013-12-01

The scope of nanotechnology is gaining importance in biology and medicine. Carbon nanotubes (CNTs) have emerged as a promising tool due to their unique properties, high specific surface area, and capacity to cross biological barriers. These properties offer a variety of opportunities for applications in nanomedicine, such as diagnosis, disease treatment, imaging, and tissue engineering. Nevertheless, pristine CNTs are insoluble in water and in most organic solvents; thereby functionalization of their surface is necessary to increase biocompatibility. Derivatization of CNTs also gives the possibility to conjugate different biological and bioactive molecules including drugs, proteins, and targeting ligands. This review focuses on the chemical modifications of CNTs that have been developed to impart specific properties for biological and medical purposes. Biomolecules can be covalently grafted or non-covalently adsorbed on the nanotube surface. In addition, the inner core of CNTs can be exploited to encapsulate drugs, nanoparticles, or radioactive elements. © 2013.

When things don't add up: quantifying impacts of multiple stressors from individual metabolism to ecosystem processing.

PubMed

Galic, Nika; Sullivan, Lauren L; Grimm, Volker; Forbes, Valery E

2018-04-01

Ecosystems are exposed to multiple stressors which can compromise functioning and service delivery. These stressors often co-occur and interact in different ways which are not yet fully understood. Here, we applied a population model representing a freshwater amphipod feeding on leaf litter in forested streams. We simulated impacts of hypothetical stressors, individually and in pairwise combinations that target the individuals' feeding, maintenance, growth and reproduction. Impacts were quantified by examining responses at three levels of biological organisation: individual-level body sizes and cumulative reproduction, population-level abundance and biomass and ecosystem-level leaf litter decomposition. Interactive effects of multiple stressors at the individual level were mostly antagonistic, that is, less negative than expected. Most population- and ecosystem-level responses to multiple stressors were stronger than expected from an additive model, that is, synergistic. Our results suggest that across levels of biological organisation responses to multiple stressors are rarely only additive. We suggest methods for efficiently quantifying impacts of multiple stressors at different levels of biological organisation. © 2018 John Wiley & Sons Ltd/CNRS.

RI: Rheology as a Tool for Understanding the Mechanics of Live Ant Aggregations, Part 2

DTIC Science & Technology

2016-11-04

measure rheological properties of biological fluids. Using this machine, we were able to characterize non-Newtonian fluids such as frog saliva...order to measure rheological properties of biological fluids. Using this machine, we were able to characterize non-Newtonian fluids such as frog...GA, 30332 Objective An Anton Parr MCR 501 rheometer was purchased in order to measure rheological properties of biological fluids. Using this

Towards first principle medical diagnostics: on the importance of disease-disease and sign-sign interactions

NASA Astrophysics Data System (ADS)

Ramezanpour, Abolfazl; Mashaghi, Alireza

2017-07-01

A fundamental problem in medicine and biology is to assign states, e.g. healthy or diseased, to cells, organs or individuals. State assignment or making a diagnosis is often a nontrivial and challenging process and, with the advent of omics technologies, the diagnostic challenge is becoming more and more serious. The challenge lies not only in the increasing number of measured properties and dynamics of the system (e.g. cell or human body) but also in the co-evolution of multiple states and overlapping properties, and degeneracy of states. We develop, from first principles, a generic rational framework for state assignment in cell biology and medicine, and demonstrate its applicability with a few simple theoretical case studies from medical diagnostics. We show how disease-related statistical information can be used to build a comprehensive model that includes the relevant dependencies between clinical and laboratory findings (signs) and diseases. In particular, we include disease-disease and sign-sign interactions and study how one can infer the probability of a disease in a patient with given signs. We perform comparative analysis with simple benchmark models to check the performances of our models. We find that including interactions can significantly change the statistical importance of the signs and diseases. This first principles approach, as we show, facilitates the early diagnosis of disease by taking interactions into accounts, and enables the construction of consensus diagnostic flow charts. Additionally, we envision that our approach will find applications in systems biology, and in particular, in characterizing the phenome via the metabolome, the proteome, the transcriptome, and the genome.

Systems Bioinformatics: increasing precision of computational diagnostics and therapeutics through network-based approaches.

PubMed

Oulas, Anastasis; Minadakis, George; Zachariou, Margarita; Sokratous, Kleitos; Bourdakou, Marilena M; Spyrou, George M

2017-11-27

Systems Bioinformatics is a relatively new approach, which lies in the intersection of systems biology and classical bioinformatics. It focuses on integrating information across different levels using a bottom-up approach as in systems biology with a data-driven top-down approach as in bioinformatics. The advent of omics technologies has provided the stepping-stone for the emergence of Systems Bioinformatics. These technologies provide a spectrum of information ranging from genomics, transcriptomics and proteomics to epigenomics, pharmacogenomics, metagenomics and metabolomics. Systems Bioinformatics is the framework in which systems approaches are applied to such data, setting the level of resolution as well as the boundary of the system of interest and studying the emerging properties of the system as a whole rather than the sum of the properties derived from the system's individual components. A key approach in Systems Bioinformatics is the construction of multiple networks representing each level of the omics spectrum and their integration in a layered network that exchanges information within and between layers. Here, we provide evidence on how Systems Bioinformatics enhances computational therapeutics and diagnostics, hence paving the way to precision medicine. The aim of this review is to familiarize the reader with the emerging field of Systems Bioinformatics and to provide a comprehensive overview of its current state-of-the-art methods and technologies. Moreover, we provide examples of success stories and case studies that utilize such methods and tools to significantly advance research in the fields of systems biology and systems medicine. © The Author 2017. Published by Oxford University Press.

Synthetic biology and intellectual property rights: six recommendations.

PubMed

Minssen, Timo; Rutz, Berthold; van Zimmeren, Esther

2015-02-01

On 26th November 2013, the Danish Agency for Science, Technology and Innovation organized an expert meeting on "Synthetic Biology & Intellectual Property Rights" in Copenhagen sponsored by the European Research Area Network in Synthetic Biology (ERASynBio). The meeting brought together ten experts from different countries with a variety of professional backgrounds to discuss emerging challenges and opportunities at the interface of synthetic biology and intellectual property rights. The aim of this article is to provide a summary of the major issues and recommendations discussed during the meeting. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An FPGA Implementation to Detect Selective Cationic Antibacterial Peptides

PubMed Central

Polanco González, Carlos; Nuño Maganda, Marco Aurelio; Arias-Estrada, Miguel; del Rio, Gabriel

2011-01-01

Exhaustive prediction of physicochemical properties of peptide sequences is used in different areas of biological research. One example is the identification of selective cationic antibacterial peptides (SCAPs), which may be used in the treatment of different diseases. Due to the discrete nature of peptide sequences, the physicochemical properties calculation is considered a high-performance computing problem. A competitive solution for this class of problems is to embed algorithms into dedicated hardware. In the present work we present the adaptation, design and implementation of an algorithm for SCAPs prediction into a Field Programmable Gate Array (FPGA) platform. Four physicochemical properties codes useful in the identification of peptide sequences with potential selective antibacterial activity were implemented into an FPGA board. The speed-up gained in a single-copy implementation was up to 108 times compared with a single Intel processor cycle for cycle. The inherent scalability of our design allows for replication of this code into multiple FPGA cards and consequently improvements in speed are possible. Our results show the first embedded SCAPs prediction solution described and constitutes the grounds to efficiently perform the exhaustive analysis of the sequence-physicochemical properties relationship of peptides. PMID:21738652

Sialic Acid-Responsive Polymeric Interface Material: From Molecular Recognition to Macroscopic Property Switching

NASA Astrophysics Data System (ADS)

Xiong, Yuting; Jiang, Ge; Li, Minmin; Qing, Guangyan; Li, Xiuling; Liang, Xinmiao; Sun, Taolei

2017-01-01

Biological systems that utilize multiple weak non-covalent interactions and hierarchical assemblies to achieve various bio-functions bring much inspiration for the design of artificial biomaterials. However, it remains a big challenge to correlate underlying biomolecule interactions with macroscopic level of materials, for example, recognizing such weak interaction, further transforming it into regulating material’s macroscopic property and contributing to some new bio-applications. Here we designed a novel smart polymer based on polyacrylamide (PAM) grafted with lactose units (PAM-g-lactose0.11), and reported carbohydrate-carbohydrate interaction (CCI)-promoted macroscopic properties switching on this smart polymer surface. Detailed investigations indicated that the binding of sialic acid molecules with the grafted lactose units via the CCIs induced conformational transformation of the polymer chains, further resulted in remarkable and reversible switching in surface topography, wettability and stiffness. With these excellent recognition and response capacities towards sialic acid, the PAM-g-lactose0.11 further facilitated good selectivity, strong anti-interference and high adsorption capacity in the capture of sialylated glycopeptides (important biomarkers for cancers). This work provides some enlightenment for the development of biointerface materials with tunable property, as well as high-performance glycopeptide enrichment materials.

Evaluation of biological properties and clinical effectiveness of Aloe vera: A systematic review

PubMed Central

Radha, Maharjan H.; Laxmipriya, Nampoothiri P.

2014-01-01

Aloe vera (蘆薈 lú huì) is well known for its considerable medicinal properties. This plant is one of the richest natural sources of health for human beings coming. The chemistry of the plant has revealed the presence of more than 200 different biologically active substances. Many biological properties associated with Aloe species are contributed by inner gel of the leaves. Most research has been centralized on the biological activities of the various species of Aloe, which include antibacterial and antimicrobial activities of the nonvolatile constituents of the leaf gel. Aloe species are widely distributed in the African and the eastern European continents, and are spread almost throughout the world. The genus Aloe has more than 400 species but few, such as A. vera, Aloe ferox, and Aloe arborescens, are globally used for trade. A. vera has various medicinal properties such as antitumor, antiarthritic, antirheumatoid, anticancer, and antidiabetic properties. In addition, A. vera has also been promoted for constipation, gastrointestinal disorders, and for immune system deficiencies. However, not much convincing information is available on properties of the gel. The present review focuses on the detailed composition of Aloe gel, its various phytocomponents having various biological properties that help to improve health and prevent disease conditions. PMID:26151005

Determination of the molecular weight of poly(ethylene glycol) in biological samples by reversed-phase LC-MS with in-source fragmentation.

PubMed

Warrack, Bethanne M; Redding, Brian P; Chen, Guodong; Bolgar, Mark S

2013-05-01

PEGylation has been widely used to improve the biopharmaceutical properties of therapeutic proteins and peptides. Previous studies have used multiple analytical techniques to determine the fate of both the therapeutic molecule and unconjugated poly(ethylene glycol) (PEG) after drug administration. A straightforward strategy utilizing liquid chromatography-mass spectrometry (LC-MS) to characterize high-molecular weight PEG in biologic matrices without a need for complex sample preparation is presented. The method is capable of determining whether high-MW PEG is cleaved in vivo to lower-molecular weight PEG species. Reversed-phase chromatographic separation is used to take advantage of the retention principles of polymeric materials whereby elution order correlates with PEG molecular weight. In-source collision-induced dissociation (CID) combined with selected reaction monitoring (SRM) or selected ion monitoring (SIM) mass spectrometry (MS) is then used to monitor characteristic PEG fragment ions in biological samples. MS provides high sensitivity and specificity for PEG and the observed retention times in reversed-phase LC enable estimation of molecular weight. This method was successfully used to characterize PEG molecular weight in mouse serum samples. No change in molecular weight was observed for 48 h after dosing.

Tensegrity, cellular biophysics, and the mechanics of living systems

PubMed Central

Ingber, Donald E.; Wang, Ning; Stamenović, Dimitrije

2014-01-01

The recent convergence between physics and biology has led many physicists to enter the fields of cell and developmental biology. One of the most exciting areas of interest has been the emerging field of mechanobiology that centers on how cells control their mechanical properties, and how physical forces regulate cellular biochemical responses, a process that is known as mechanotransduction. In this article, we review the central role that tensegrity (tensional integrity) architecture, which depends on tensile prestress for its mechanical stability, plays in biology. We describe how tensional prestress is a critical governor of cell mechanics and function, and how use of tensegrity by cells contributes to mechanotransduction. Theoretical tensegrity models are also described that predict both quantitative and qualitative behaviors of living cells, and these theoretical descriptions are placed in context of other physical models of the cell. In addition, we describe how tensegrity is used at multiple size scales in the hierarchy of life — from individual molecules to whole living organisms — to both stabilize three-dimensional form and to channel forces from the macroscale to the nanoscale, thereby facilitating mechanochemical conversion at the molecular level. PMID:24695087

Detection of 224 candidate structured RNAs by comparative analysis of specific subsets of intergenic regions

PubMed Central

Lünse, Christina E.; Corbino, Keith A.; Ames, Tyler D.; Nelson, James W.; Roth, Adam; Perkins, Kevin R.; Sherlock, Madeline E.

2017-01-01

Abstract The discovery of structured non-coding RNAs (ncRNAs) in bacteria can reveal new facets of biology and biochemistry. Comparative genomics analyses executed by powerful computer algorithms have successfully been used to uncover many novel bacterial ncRNA classes in recent years. However, this general search strategy favors the discovery of more common ncRNA classes, whereas progressively rarer classes are correspondingly more difficult to identify. In the current study, we confront this problem by devising several methods to select subsets of intergenic regions that can concentrate these rare RNA classes, thereby increasing the probability that comparative sequence analysis approaches will reveal their existence. By implementing these methods, we discovered 224 novel ncRNA classes, which include ROOL RNA, an RNA class averaging 581 nt and present in multiple phyla, several highly conserved and widespread ncRNA classes with properties that suggest sophisticated biochemical functions and a multitude of putative cis-regulatory RNA classes involved in a variety of biological processes. We expect that further research on these newly found RNA classes will reveal additional aspects of novel biology, and allow for greater insights into the biochemistry performed by ncRNAs. PMID:28977401

Self-organization versus Watchmaker: ambiguity of molecular recognition and design charts of cellular circuitry.

PubMed

Kurakin, Alexei

2007-01-01

A large body of experimental evidence indicates that the specific molecular interactions and/or chemical conversions depicted as links in the conventional diagrams of cellular signal transduction and metabolic pathways are inherently probabilistic, ambiguous and context-dependent. Being the inevitable consequence of the dynamic nature of protein structure in solution, the ambiguity of protein-mediated interactions and conversions challenges the conceptual adequacy and practical usefulness of the mechanistic assumptions and inferences embodied in the design charts of cellular circuitry. It is argued that the reconceptualization of molecular recognition and cellular organization within the emerging interpretational framework of self-organization, which is expanded here to include such concepts as bounded stochasticity, evolutionary memory, and adaptive plasticity offers a significantly more adequate representation of experimental reality than conventional mechanistic conceptions do. Importantly, the expanded framework of self-organization appears to be universal and scale-invariant, providing conceptual continuity across multiple scales of biological organization, from molecules to societies. This new conceptualization of biological phenomena suggests that such attributes of intelligence as adaptive plasticity, decision-making, and memory are enforced by evolution at different scales of biological organization and may represent inherent properties of living matter. (c) 2007 John Wiley & Sons, Ltd.

Do Houseflies Think? Patterns of Induction and Biological Beliefs in Development.

ERIC Educational Resources Information Center

Gutheil, Grant; Vera, Alonzo; Keil, Frank C.

1998-01-01

Examined preschoolers' inductive inferences across biological and non-biological kinds. Found support for gradual-enrichment model of conceptual change. Four-year-olds had a limited, coherent, independent biological theory which may form the basis of mature understanding of biological kinds. Explored results in terms of multiple explanatory…

Sulforaphane suppresses lipopolysaccharide-induced cyclooxygenase-2 (COX-2) expression through the modulation of multiple targets in COX-2 gene promoter.

PubMed

Woo, Kyung Jin; Kwon, Taeg Kyu

2007-12-15

Sulforaphane is a natural, biologically active compound extracted from cruciferous vegetables such as broccoli and cabbage. It possesses potent anti-inflammation and anti-cancer properties. The mechanism by which sulforaphane suppresses COX-2 expression remains poorly understood. In the present report, we investigated the effect of sulforaphane on the expression of COX-2 in lipopolysaccharide (LPS)-activated Raw 264.7 cells. Sulforaphane significantly suppressed the LPS-induced COX-2 protein and mRNA expression in a dose-dependent manner. The ability of sulforaphane to suppress the expression of the COX-2 was investigated using luciferase reporters controlled by various cis-elements in COX-2 promoter region. Electrophoretic mobility shift assay (EMSA) verified that NF-kappaB, C/EBP, CREB and AP-1 were identified as responsible for the sulforaphane-mediated COX-2 down-regulation. In addition, we demonstrated the signal transduction pathway of mitogen-activated protein kinase (MAP kinase) in LPS-induced COX-2 expression. Taken together, these results demonstrate that sulforaphane effectively suppressed the LPS-induced COX-2 protein via modulation of multiple core promoter elements (NF-kappaB, C/EBP, CREB and AP-1) in the COX-2 transcriptional regulation. These results will provide new insights into the anti-inflammatory and anti-carcinogenic properties of sulforaphane.

Scaffold explorer: an interactive tool for organizing and mining structure-activity data spanning multiple chemotypes.

PubMed

Agrafiotis, Dimitris K; Wiener, John J M

2010-07-08

We introduce Scaffold Explorer, an interactive tool that allows medicinal chemists to define hierarchies of chemical scaffolds and use them to explore their project data. Scaffold Explorer allows the user to construct a tree, where each node corresponds to a specific scaffold. Each node can have multiple children, each of which represents a more refined substructure relative to its parent node. Once the tree is defined, it can be mapped onto any collection of compounds and be used as a navigational tool to explore structure-activity relationships (SAR) across different chemotypes. The rich visual analytics of Scaffold Explorer afford the user a "bird's-eye" view of the chemical space spanned by a particular data set, map any physicochemical property or biological activity of interest onto the individual scaffold nodes, serve as an aggregator for the properties of the compounds represented by these nodes, and quickly distinguish promising chemotypes from less interesting or problematic ones. Unlike previous approaches, which focused on automated extraction and classification of scaffolds, the utility of the new tool rests on its interactivity and ability to accommodate the medicinal chemists' intuition by allowing the use of arbitrary substructures containing variable atoms, bonds, and/or substituents such as those employed in substructure search.

Relationship between the Increased Haemostatic Properties of Blood Platelets and Oxidative Stress Level in Multiple Sclerosis Patients with the Secondary Progressive Stage.

PubMed

Morel, Agnieszka; Bijak, Michał; Miller, Elżbieta; Rywaniak, Joanna; Miller, Sergiusz; Saluk, Joanna

2015-01-01

Multiple sclerosis (MS) is the autoimmune disease of the central nervous system with complex pathogenesis, different clinical courses and recurrent neurological relapses and/or progression. Despite various scientific papers that focused on early stage of MS, our study targets selective group of late stage secondary progressive MS patients. The presented work is concerned with the reactivity of blood platelets in primary hemostasis in SP MS patients. 50 SP MS patients and 50 healthy volunteers (never diagnosed with MS or other chronic diseases) were examined to evaluate the biological activity of blood platelets (adhesion, aggregation), especially their response to the most important physiological agonists (thrombin, ADP, and collagen) and the effect of oxidative stress on platelet activity. We found that the blood platelets from SP MS patients were significantly more sensitive to all used agonists in comparison with control group. Moreover, the platelet hemostatic function was advanced in patients suffering from SP MS and positively correlated with increased production of O2 (-∙) in these cells, as well as with Expanded Disability Status Scale. We postulate that the increased oxidative stress in blood platelets in SP MS may be primarily responsible for the altered haemostatic properties of blood platelets.

Relationship between the Increased Haemostatic Properties of Blood Platelets and Oxidative Stress Level in Multiple Sclerosis Patients with the Secondary Progressive Stage

PubMed Central

Bijak, Michał; Miller, Elżbieta; Miller, Sergiusz

2015-01-01

Multiple sclerosis (MS) is the autoimmune disease of the central nervous system with complex pathogenesis, different clinical courses and recurrent neurological relapses and/or progression. Despite various scientific papers that focused on early stage of MS, our study targets selective group of late stage secondary progressive MS patients. The presented work is concerned with the reactivity of blood platelets in primary hemostasis in SP MS patients. 50 SP MS patients and 50 healthy volunteers (never diagnosed with MS or other chronic diseases) were examined to evaluate the biological activity of blood platelets (adhesion, aggregation), especially their response to the most important physiological agonists (thrombin, ADP, and collagen) and the effect of oxidative stress on platelet activity. We found that the blood platelets from SP MS patients were significantly more sensitive to all used agonists in comparison with control group. Moreover, the platelet hemostatic function was advanced in patients suffering from SP MS and positively correlated with increased production of O2 −∙ in these cells, as well as with Expanded Disability Status Scale. We postulate that the increased oxidative stress in blood platelets in SP MS may be primarily responsible for the altered haemostatic properties of blood platelets. PMID:26064417

Biological and nonbiological complex drugs for multiple sclerosis in Latin America: regulations and risk management.

PubMed

Carrá, Adriana; Macías Islas, Miguel Angel; Tarulla, Adriana; Bichuetti, Denis Bernardi; Finkelsztejn, Alessandro; Fragoso, Yara Dadalti; Árcega-Revilla, Raul; Cárcamo Rodríguez, Claudia; Durán, Juan Carlos; Bonitto, Juan García; León, Rosalba; Oehninger Gatti, Carlos; Orozco, Geraldine; Vizcarra Escobar, Darwin

2015-06-01

Biological drugs and nonbiological complex drugs with expired patents are followed by biosimilars and follow-on drugs that are supposedly similar and comparable with the reference product in terms of quality, safety and efficacy. Unlike simple molecules that can be copied and reproduced, biosimilars and follow-on complex drugs are heterogeneous and need specific regulations from health and pharmacovigilance agencies. A panel of 14 Latin American experts on multiple sclerosis from nine different countries met to discuss the recommendations regarding biosimilars and follow-on complex drugs for treating multiple sclerosis. Specific measures relating to manufacturing, therapeutic equivalence assessment and pharmacovigilance reports need to be implemented before commercialization. Physical, chemical, biological and immunogenic characterizations of the new product need to be available before clinical trials start. The new product must maintain the same immunogenicity as the original. Automatic substitution of biological and complex drugs poses unacceptable risks to the patient.

3D printing of tissue-simulating phantoms as a traceable standard for biomedical optical measurement

NASA Astrophysics Data System (ADS)

Dong, Erbao; Wang, Minjie; Shen, Shuwei; Han, Yilin; Wu, Qiang; Xu, Ronald

2016-01-01

Optical phantoms are commonly used to validate and calibrate biomedical optical devices in order to ensure accurate measurement of optical properties in biological tissue. However, commonly used optical phantoms are based on homogenous materials that reflect neither optical properties nor multi-layer heterogeneities of biological tissue. Using these phantoms for optical calibration may result in significant bias in biological measurement. We propose to characterize and fabricate tissue simulating phantoms that simulate not only the multi-layer heterogeneities but also optical properties of biological tissue. The tissue characterization module detects tissue structural and functional properties in vivo. The phantom printing module generates 3D tissue structures at different scales by layer-by-layer deposition of phantom materials with different optical properties. The ultimate goal is to fabricate multi-layer tissue simulating phantoms as a traceable standard for optimal calibration of biomedical optical spectral devices.

Effectiveness and biological compatibility of different generations of dentin adhesives.

PubMed

da Silva, João M F; Rodrigues, José R; Camargo, Carlos H R; Fernandes, Virgilio Vilas Boas; Hiller, Karl-Anton; Schweikl, Helmut; Schmalz, Gottfried

2014-01-01

Besides possessing good mechanical properties, dental materials should present a good biological behavior and should not injure the involved tissues. Bond strength and biocompatibility are both highly significant properties of dentin adhesives. For that matter, these properties of four generations of adhesive systems (Multi-Purpose/Single Bond/SE Plus/Easy Bond) were evaluated. Eighty bovine teeth had their dentin exposed (500- and 200-μm thickness). Adhesive was applied on the dentin layer of each specimen. Following that, the microshearing test was performed for all samples. A dentin barrier test was used for the cytotoxicity evaluation. Cell cultures (SV3NeoB) were collected from testing materials by means of 200- or 500-μm-thick dentin slices and placed in a cell culture perfusion chamber. Cell viability was measured 24 h post-exposition by means of a photometrical test (MTT test). The best bonding performance was shown by the single-step adhesive Easy Bond (21 MPa, 200 μm; 27 MPa, 500 μm) followed by Single Bond (15.6 MPa, 200 μm; 23.4 MPa, 500 μm), SE Plus (18.2 MPa, 200 μm; 20 MPa, 500 μm), and Multi-Purpose (15.2 MPa, 200 μm; 17.9 MPa, 500 μm). Regarding the cytotoxicity, Multi-Purpose slightly reduced the cell viability to 92% (200 μm)/93% (500 μm). Single Bond was reasonably cytotoxic, reducing cell viability to 71% (200 μm)/64% (500 μm). The self-etching adhesive Scotchbond SE decreased cell viability to 85% (200 μm)/71% (500 μm). Conversely, Easy Bond did not reduce cell viability in this test, regardless of the dentin thickness. Results showed that the one-step system had the best bond strength performance and was the least toxic to pulp cells. In multiple-step systems, a correct bonding technique must be done, and a pulp capping strategy is necessary for achieving good performance in both properties. The study showed a promising system (one-step self-etching), referring to it as a good alternative for specific cases, mainly due to its technical simplicity and good biological responses.

Fucaceae: A Source of Bioactive Phlorotannins

PubMed Central

Catarino, Marcelo D.; Silva, Artur M. S.; Cardoso, Susana M.

2017-01-01

Fucaceae is the most dominant algae family along the intertidal areas of the Northern Hemisphere shorelines, being part of human customs for centuries with applications as a food source either for humans or animals, in agriculture and as remedies in folk medicine. These macroalgae are endowed with several phytochemicals of great industrial interest from which phlorotannins, a class of marine-exclusive polyphenols, have gathered much attention during the last few years due to their numerous possible therapeutic properties. These compounds are very abundant in brown seaweeds such as Fucaceae and have been demonstrated to possess numerous health-promoting properties, including antioxidant effects through scavenging of reactive oxygen species (ROS) or enhancement of intracellular antioxidant defenses, antidiabetic properties through their acarbose-like activity, stimulation of adipocytes glucose uptake and protection of β-pancreatic cells against high-glucose oxidative stress; anti-inflammatory effects through inhibition of several pro-inflammatory mediators; antitumor properties by activation of apoptosis on cancerous cells and metastasis inhibition, among others. These multiple health properties render phlorotannins great potential for application in numerous therapeutical approaches. This review addresses the major contribution of phlototannins for the biological effects that have been described for seaweeds from Fucaceae. In addition, the bioavailability of this group of phenolic compounds is discussed. PMID:28635652

Ferromagnetic nanoparticles containing biologically active alkanolamines: preparation and properties

NASA Astrophysics Data System (ADS)

Segal, I.; Zablotskaya, A.; Lukevics, E.; Maiorov, M.; Zablotsky, D.

2005-12-01

The objective of the present study is to investigate the possibility of sorption on ultrafine magnetic particles of some model biologically active organosilicon alkanolamines, structural analogs of natural biologically active substances, choline and colamine, with increased lipophilicity. Double-coated ferromagnetic samples containing oleic acid, as a first layer, and organosilicon alcanolamines, as a second layer, were obtained and characterized by their physical/chemical (sorption and magnetisation) and biological (toxicity and cytotoxicity) properties. The present results clearly reveal the sorption of the biologically active alkanolamines on the surface of magnetic particles and a principal possibility to coat magnetite directly with biologically active alkanolamines, creating a mono-layer cover. The data presented in the study of cytotoxic properties of the newly obtained ferromagnetic nanoparticles show that it is reasonable to investigate such systems as potential cytotoxic agents. Tables 3, Figs 3, Refs 16.

Bacterial Microcolonies in Gel Beads for High-Throughput Screening of Libraries in Synthetic Biology.

PubMed

Duarte, José M; Barbier, Içvara; Schaerli, Yolanda

2017-11-17

Synthetic biologists increasingly rely on directed evolution to optimize engineered biological systems. Applying an appropriate screening or selection method for identifying the potentially rare library members with the desired properties is a crucial step for success in these experiments. Special challenges include substantial cell-to-cell variability and the requirement to check multiple states (e.g., being ON or OFF depending on the input). Here, we present a high-throughput screening method that addresses these challenges. First, we encapsulate single bacteria into microfluidic agarose gel beads. After incubation, they harbor monoclonal bacterial microcolonies (e.g., expressing a synthetic construct) and can be sorted according their fluorescence by fluorescence activated cell sorting (FACS). We determine enrichment rates and demonstrate that we can measure the average fluorescent signals of microcolonies containing phenotypically heterogeneous cells, obviating the problem of cell-to-cell variability. Finally, we apply this method to sort a pBAD promoter library at ON and OFF states.

Disorder in convergent floral nanostructures enhances signalling to bees

NASA Astrophysics Data System (ADS)

Moyroud, Edwige; Wenzel, Tobias; Middleton, Rox; Rudall, Paula J.; Banks, Hannah; Reed, Alison; Mellers, Greg; Killoran, Patrick; Westwood, M. Murphy; Steiner, Ullrich; Vignolini, Silvia; Glover, Beverley J.

2017-10-01

Diverse forms of nanoscale architecture generate structural colour and perform signalling functions within and between species. Structural colour is the result of the interference of light from approximately regular periodic structures; some structural disorder is, however, inevitable in biological organisms. Is this disorder functional and subject to evolutionary selection, or is it simply an unavoidable outcome of biological developmental processes? Here we show that disordered nanostructures enable flowers to produce visual signals that are salient to bees. These disordered nanostructures (identified in most major lineages of angiosperms) have distinct anatomies but convergent optical properties; they all produce angle-dependent scattered light, predominantly at short wavelengths (ultraviolet and blue). We manufactured artificial flowers with nanoscale structures that possessed tailored levels of disorder in order to investigate how foraging bumblebees respond to this optical effect. We conclude that floral nanostructures have evolved, on multiple independent occasions, an effective degree of relative spatial disorder that generates a photonic signature that is highly salient to insect pollinators.

Challenges and dreams: physics of weak interactions essential to life

PubMed Central

Chien, Peter; Gierasch, Lila M.

2014-01-01

Biological systems display stunning capacities to self-organize. Moreover, their subcellular architectures are dynamic and responsive to changing needs and conditions. Key to these properties are manifold weak “quinary” interactions that have evolved to create specific spatial networks of macromolecules. These specific arrangements of molecules enable signals to be propagated over distances much greater than molecular dimensions, create phase separations that define functional regions in cells, and amplify cellular responses to changes in their environments. A major challenge is to develop biochemical tools and physical models to describe the panoply of weak interactions operating in cells. We also need better approaches to measure the biases in the spatial distributions of cellular macromolecules that result from the integrated action of multiple weak interactions. Partnerships between cell biologists, biochemists, and physicists are required to deploy these methods. Together these approaches will help us realize the dream of understanding the biological “glue” that sustains life at a molecular and cellular level. PMID:25368424

Inter-Annual and Shorter-Term Variability in Physical and Biological Characteristics Across Barrow Canyon in August - September 2005-2014

NASA Astrophysics Data System (ADS)

Ashjian, C. J.; Okkonen, S. R.; Campbell, R. G.; Alatalo, P.

2014-12-01

Late summer physical and biological conditions along a 37-km transect crossing Barrow Canyon have been described for the past ten years as part of an ongoing program, supported by multiple funding sources including the NSF AON, focusing on inter-annual variability and the formation of a bowhead whale feeding hotspot near Barrow. These repeated transects (at least two per year, separated in time by days-weeks) provide an opportunity to assess the inter-annual and shorter term (days-weeks) changes in hydrographic structure, ocean temperature, current velocity and transport, chlorophyll fluorescence, nutrients, and micro- and mesozooplankton community composition and abundance. Inter-annual variability in all properties was high and was associated with larger scale, meteorological forcing. Shorter-term variability could also be high but was strongly influenced by changes in local wind forcing. The sustained sampling at this location provided critical measures of inter-annual variability that should permit detection of longer-term trends that are associated with ongoing climate change.

[Effects of fibronectin on cytodifferentiation (T56) of human squamous cell carcinoma of tongue].

PubMed

Huang, Y; Yang, F

1994-12-01

Fibronectin (FN) are large glycoproteins that have been implicated in a wide variety of cellular properties, including cell adhesion, morphology, cytoskeletal organization, migration, differentiation, and oncogenic transformation. T56 cells were treated with 20, 50, and 100 micrograms/ml of FN for 48 h, and the changes in cells were analysed qualitatively and quantitatively with the methods of transmission electron microscopy, enzyme cytochemistry, and cell electrophoresis, etc. The studies were made to test the effects of FN on T56 cells in biological behaviour in terms of cell growth, multiplication, cell metabolism, cell electrophoresis and surface morphology. The results indicated that FN could partially restore T56 cell normal epidermic cell's phenotype, inhibit cell mitosis, increase contact of cells, decrease the number of microvilli and ruffles, and promote cell oxybiotic metabolism. These results suggest that FN might relate in many aspects to the biological behaviour of T56 cell and could affect changes in the behaviour.

Characterising meso-marine ecosystems of the North Pacific

NASA Astrophysics Data System (ADS)

Batten, Sonia D.; David Hyrenbach, K.; Sydeman, William J.; Morgan, Ken H.; Henry, Michael F.; Yen, Peggy P. Y.; Welch, David W.

2006-02-01

To delineate mesoscale variability in marine ecosystems of the subarctic North Pacific and identify "hotspots" of biological activity, we conducted contemporaneous surveys of plankton and avifaunal communites in 2000-2003. Plankton samples were collected with a continuous plankton recorder (CPR) towed by a commercial vessel while a trained observer recorded marine bird distributions using strip-transect techniques. Near- and sub-surface physical oceanographic properties and productivity patterns were measured using a temperature data logger and satellite-derived chlorophyll a concentrations. We identified 10 distinct biological communities across the North Pacific, which we refer to as 'meso-marine ecosystems' (MME). We examined the characteristics of MME over multiple years to assess temporal persistence. MME were associated with different bathymetric domains and current systems. MME differed in the overall abundance and species composition of their fauna and, therefore, almost certainly in productivity. Regular monitoring of the spatial and temporal variability of MME will enhance our ability to detect and understand coupled climate-ecosystem responses, and, in turn, help guide ecosystem-based fisheries and wildlife management.

Involvement of the nitric oxide in melatonin-mediated protection against injury.

PubMed

Fan, Wenguo; He, Yifan; Guan, Xiaoyan; Gu, Wenzhen; Wu, Zhi; Zhu, Xiao; Huang, Fang; He, Hongwen

2018-05-01

Melatonin is a hormone mainly synthesized by the pineal gland in vertebrates and known well as an endogenous regulator of circadian and seasonal rhythms. It has been demonstrated that melatonin is involved in many physiological and pathophysiological processes showing antioxidant, anti-apoptotic and anti-inflammatory properties. Nitric oxide (NO) is a free radical gas in the biological system, which is produced by nitric oxide synthase (NOS) family. NO acts as a biological mediator and plays important roles in different systems in humans. The NO/NOS system exerts a broad spectrum of signaling functions. Accumulating evidence has clearly revealed that melatonin regulates NO/NOS system through multiple mechanisms that may influence physiological and pathophysiological processes. This article reviews the latest evidence for the effects of melatonin on NO/NOS regulation in different organs and disease conditions, the potential cellular mechanisms by which melatonin is involved in organ protection are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Modifications of pancreatic diffusion MRI by tissue characteristics: what are we weighting for?

PubMed

Nissan, Noam

2017-08-01

Diffusion-weighted imaging holds the potential to improve the diagnosis and biological characterization of pancreatic disease, and in particular pancreatic cancer, which exhibits decreased values of the apparent diffusion coefficient (ADC). Yet, variable and overlapping ADC values have been reported for the healthy and the pathological pancreas, including for cancer and other benign conditions. This controversy reflects the complexity of probing the water-diffusion process in the pancreas, which is dependent upon multiple biological factors within this organ's unique physiological environment. In recent years, extensive studies have investigated the correlation between tissue properties including cellularity, vascularity, fibrosis, secretion and microstructure and pancreatic diffusivity. Understanding how the various physiological and pathological features and the underlying functional processes affect the diffusion measurement may serve to optimize the method for improved diagnostic gain. Therefore, the aim of the present review article is to elucidate the relationship between pancreatic tissue characteristics and diffusion MRI measurement. Copyright © 2017 John Wiley & Sons, Ltd.

Evolving phenotypic networks in silico.

PubMed

François, Paul

2014-11-01

Evolved gene networks are constrained by natural selection. Their structures and functions are consequently far from being random, as exemplified by the multiple instances of parallel/convergent evolution. One can thus ask if features of actual gene networks can be recovered from evolutionary first principles. I review a method for in silico evolution of small models of gene networks aiming at performing predefined biological functions. I summarize the current implementation of the algorithm, insisting on the construction of a proper "fitness" function. I illustrate the approach on three examples: biochemical adaptation, ligand discrimination and vertebrate segmentation (somitogenesis). While the structure of the evolved networks is variable, dynamics of our evolved networks are usually constrained and present many similar features to actual gene networks, including properties that were not explicitly selected for. In silico evolution can thus be used to predict biological behaviours without a detailed knowledge of the mapping between genotype and phenotype. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

Exact dynamic properties of molecular motors

NASA Astrophysics Data System (ADS)

Boon, N. J.; Hoyle, R. B.

2012-08-01

Molecular motors play important roles within a biological cell, performing functions such as intracellular transport and gene transcription. Recent experimental work suggests that there are many plausible biochemical mechanisms that molecules such as myosin-V could use to achieve motion. To account for the abundance of possible discrete-stochastic frameworks that can arise when modeling molecular motor walks, a generalized and straightforward graphical method for calculating their dynamic properties is presented. It allows the calculation of the velocity, dispersion, and randomness ratio for any proposed system through analysis of its structure. This article extends work of King and Altman ["A schematic method of deriving the rate laws of enzyme-catalyzed reactions," J. Phys. Chem. 60, 1375-1378 (1956)], 10.1021/j150544a010 on networks of enzymatic reactions by calculating additional dynamic properties for spatially hopping systems. Results for n-state systems are presented: single chain, parallel pathway, divided pathway, and divided pathway with a chain. A novel technique for combining multiple system architectures coupled at a reference state is also demonstrated. Four-state examples illustrate the effectiveness and simplicity of these methods.

Underwater Inherent Optical Properties Estimation Using a Depth Aided Deep Neural Network.

PubMed

Yu, Zhibin; Wang, Yubo; Zheng, Bing; Zheng, Haiyong; Wang, Nan; Gu, Zhaorui

2017-01-01

Underwater inherent optical properties (IOPs) are the fundamental clues to many research fields such as marine optics, marine biology, and underwater vision. Currently, beam transmissometers and optical sensors are considered as the ideal IOPs measuring methods. But these methods are inflexible and expensive to be deployed. To overcome this problem, we aim to develop a novel measuring method using only a single underwater image with the help of deep artificial neural network. The power of artificial neural network has been proved in image processing and computer vision fields with deep learning technology. However, image-based IOPs estimation is a quite different and challenging task. Unlike the traditional applications such as image classification or localization, IOP estimation looks at the transparency of the water between the camera and the target objects to estimate multiple optical properties simultaneously. In this paper, we propose a novel Depth Aided (DA) deep neural network structure for IOPs estimation based on a single RGB image that is even noisy. The imaging depth information is considered as an aided input to help our model make better decision.

Biological functions of iduronic acid in chondroitin/dermatan sulfate

PubMed Central

Thelin, Martin A; Bartolini, Barbara; Axelsson, Jakob; Gustafsson, Renata; Tykesson, Emil; Pera, Edgar; Oldberg, Åke; Maccarana, Marco; Malmstrom, Anders

2013-01-01

The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides because it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties, such as migration, proliferation, differentiation, angiogenesis and the regulation of cytokine/growth factor activities. Under pathological conditions such as wound healing, inflammation and cancer, iduronic acid has diverse regulatory functions. Iduronic acid is formed by two epimerases (i.e. dermatan sulfate epimerase 1 and 2) that have different tissue distribution and properties. The role of iduronic acid in chondroitin/dermatan sulfate is highlighted by the vast changes in connective tissue features in patients with a new type of Ehler–Danlos syndrome: adducted thumb-clubfoot syndrome. Future research aims to understand the roles of the two epimerases and their interplay with the sulfotransferases involved in chondroitin sulfate/dermatan sulfate biosynthesis. Furthermore, a better definition of chondroitin/dermatan sulfate functions using different knockout models is needed. In this review, we focus on the two enzymes responsible for iduronic acid formation, as well as the role of iduronic acid in health and disease. PMID:23441919

Combined, solid-state molecular property and gamma spectrometers for CBRNE detection

NASA Astrophysics Data System (ADS)

Rogers, Ben; Grate, Jay; Pearson, Brett; Gallagher, Neal; Wise, Barry; Whitten, Ralph; Adams, Jesse

2013-05-01

Nevada Nanotech Systems, Inc. (Nevada Nano) has developed a multi-sensor solution to Chemical, Biological, Radiological, Nuclear and Explosives (CBRNE) detection that combines the Molecular Property Spectrometer™ (MPS™)—a micro-electro-mechanical chip-based technology capable of measuring a variety of thermodynamic and electrostatic molecular properties of sampled vapors and particles—and a compact, high-resolution, solid-state gamma spectrometer module for identifying radioactive materials, including isotopes used in dirty bombs and nuclear weapons. By conducting multiple measurements, the system can provide a more complete characterization of an unknown sample, leading to a more accurate identification. Positive identifications of threats are communicated using an integrated wireless module. Currently, system development is focused on detection of commercial, military and improvised explosives, radioactive materials, and chemical threats. The system can be configured for a variety of CBRNE applications, including handheld wands and swab-type threat detectors requiring short sample times, and ultra-high sensitivity detectors in which longer sampling times are used. Here we provide an overview of the system design and operation and present results from preliminary testing.

Smarten

NASA Astrophysics Data System (ADS)

Metcalfe, C.; Bennett, E.; Chappell, M.; Steevens, J.; Depledge, M.; Goss, G.; Goudey, S.; Kaczmar, S.; O'Brien, N.; Picado, A.; Ramadan, A. B.

Traditional risk assessment procedures are inadequate for predicting the ecological risks associated with the release of nanomaterials (NM) into the environment. The root of the problem lies in an inadequate application of solid phase chemical principles (e.g. particle size, shape, functionality) for the risk assessment of NMs. Thus, the "solubility" paradigm used to evaluate the risks associated with other classes of contaminants must be replaced by a "dispersivity" paradigm for evaluating the risks associated with NM. The pace of development of NM will exceed the capacity to conduct adequate risk assessments using current methods and approaches. Each NM product will be available in a variety of size classes and with different surface functionalizations; probably requiring multiple risk assessments for each NM. The "SMARTEN" approach to risk assessment involves having risk assessors play a more proactive role in evaluating all aspects of the NM life cycle and in making decisions to develop lower risk NM products. Improved problem formulation could come from considering the chemical, physical and biological properties of NMs. New effects assessment techniques are needed to evaluate cellular binding and uptake potential, such as biological assays for binding to macromolecules or organelles, phagocytic activity, and active/passive uptake processes. Tests should be developed to evaluate biological effects with multiple species across a range of trophic levels. Despite our best efforts to assess the risks associated with NM, previous experience indicates that some NM products will enter the environment and cause biological effects. Therefore, risk assessors should support programs for reconnaissance and surveillance to detect the impacts of NM before irreversible damage occurs. New analytical tools are needed for surveillance, including sensors for detecting NMs, passive sampling systems, and improved methods for separation and characterization of NMs in environmental matrices, as well as biomarker techniques to evaluate exposure to NMs. Risk assessors should use this information to refine data quality, determine future risk assessment objectives and to communicate interim conclusions to a wide group of stakeholders.1

Neuromorphic neural interfaces: from neurophysiological inspiration to biohybrid coupling with nervous systems

NASA Astrophysics Data System (ADS)

Broccard, Frédéric D.; Joshi, Siddharth; Wang, Jun; Cauwenberghs, Gert

2017-08-01

Objective. Computation in nervous systems operates with different computational primitives, and on different hardware, than traditional digital computation and is thus subjected to different constraints from its digital counterpart regarding the use of physical resources such as time, space and energy. In an effort to better understand neural computation on a physical medium with similar spatiotemporal and energetic constraints, the field of neuromorphic engineering aims to design and implement electronic systems that emulate in very large-scale integration (VLSI) hardware the organization and functions of neural systems at multiple levels of biological organization, from individual neurons up to large circuits and networks. Mixed analog/digital neuromorphic VLSI systems are compact, consume little power and operate in real time independently of the size and complexity of the model. Approach. This article highlights the current efforts to interface neuromorphic systems with neural systems at multiple levels of biological organization, from the synaptic to the system level, and discusses the prospects for future biohybrid systems with neuromorphic circuits of greater complexity. Main results. Single silicon neurons have been interfaced successfully with invertebrate and vertebrate neural networks. This approach allowed the investigation of neural properties that are inaccessible with traditional techniques while providing a realistic biological context not achievable with traditional numerical modeling methods. At the network level, populations of neurons are envisioned to communicate bidirectionally with neuromorphic processors of hundreds or thousands of silicon neurons. Recent work on brain-machine interfaces suggests that this is feasible with current neuromorphic technology. Significance. Biohybrid interfaces between biological neurons and VLSI neuromorphic systems of varying complexity have started to emerge in the literature. Primarily intended as a computational tool for investigating fundamental questions related to neural dynamics, the sophistication of current neuromorphic systems now allows direct interfaces with large neuronal networks and circuits, resulting in potentially interesting clinical applications for neuroengineering systems, neuroprosthetics and neurorehabilitation.

Design, synthesis and applications of core-shell, hollow core, and nanorattle multifunctional nanostructures.

PubMed

El-Toni, Ahmed Mohamed; Habila, Mohamed A; Labis, Joselito Puzon; ALOthman, Zeid A; Alhoshan, Mansour; Elzatahry, Ahmed A; Zhang, Fan

2016-02-07

With the evolution of nanoscience and nanotechnology, studies have been focused on manipulating nanoparticle properties through the control of their size, composition, and morphology. As nanomaterial research has progressed, the foremost focus has gradually shifted from synthesis, morphology control, and characterization of properties to the investigation of function and the utility of integrating these materials and chemical sciences with the physical, biological, and medical fields, which therefore necessitates the development of novel materials that are capable of performing multiple tasks and functions. The construction of multifunctional nanomaterials that integrate two or more functions into a single geometry has been achieved through the surface-coating technique, which created a new class of substances designated as core-shell nanoparticles. Core-shell materials have growing and expanding applications due to the multifunctionality that is achieved through the formation of multiple shells as well as the manipulation of core/shell materials. Moreover, core removal from core-shell-based structures offers excellent opportunities to construct multifunctional hollow core architectures that possess huge storage capacities, low densities, and tunable optical properties. Furthermore, the fabrication of nanomaterials that have the combined properties of a core-shell structure with that of a hollow one has resulted in the creation of a new and important class of substances, known as the rattle core-shell nanoparticles, or nanorattles. The design strategies of these new multifunctional nanostructures (core-shell, hollow core, and nanorattle) are discussed in the first part of this review. In the second part, different synthesis and fabrication approaches for multifunctional core-shell, hollow core-shell and rattle core-shell architectures are highlighted. Finally, in the last part of the article, the versatile and diverse applications of these nanoarchitectures in catalysis, energy storage, sensing, and biomedicine are presented.

Association between expression of random gene sets and survival is evident in multiple cancer types and may be explained by sub-classification.

PubMed

Shimoni, Yishai

2018-02-01

One of the goals of cancer research is to identify a set of genes that cause or control disease progression. However, although multiple such gene sets were published, these are usually in very poor agreement with each other, and very few of the genes proved to be functional therapeutic targets. Furthermore, recent findings from a breast cancer gene-expression cohort showed that sets of genes selected randomly can be used to predict survival with a much higher probability than expected. These results imply that many of the genes identified in breast cancer gene expression analysis may not be causal of cancer progression, even though they can still be highly predictive of prognosis. We performed a similar analysis on all the cancer types available in the cancer genome atlas (TCGA), namely, estimating the predictive power of random gene sets for survival. Our work shows that most cancer types exhibit the property that random selections of genes are more predictive of survival than expected. In contrast to previous work, this property is not removed by using a proliferation signature, which implies that proliferation may not always be the confounder that drives this property. We suggest one possible solution in the form of data-driven sub-classification to reduce this property significantly. Our results suggest that the predictive power of random gene sets may be used to identify the existence of sub-classes in the data, and thus may allow better understanding of patient stratification. Furthermore, by reducing the observed bias this may allow more direct identification of biologically relevant, and potentially causal, genes.

Association between expression of random gene sets and survival is evident in multiple cancer types and may be explained by sub-classification

PubMed Central

2018-01-01

One of the goals of cancer research is to identify a set of genes that cause or control disease progression. However, although multiple such gene sets were published, these are usually in very poor agreement with each other, and very few of the genes proved to be functional therapeutic targets. Furthermore, recent findings from a breast cancer gene-expression cohort showed that sets of genes selected randomly can be used to predict survival with a much higher probability than expected. These results imply that many of the genes identified in breast cancer gene expression analysis may not be causal of cancer progression, even though they can still be highly predictive of prognosis. We performed a similar analysis on all the cancer types available in the cancer genome atlas (TCGA), namely, estimating the predictive power of random gene sets for survival. Our work shows that most cancer types exhibit the property that random selections of genes are more predictive of survival than expected. In contrast to previous work, this property is not removed by using a proliferation signature, which implies that proliferation may not always be the confounder that drives this property. We suggest one possible solution in the form of data-driven sub-classification to reduce this property significantly. Our results suggest that the predictive power of random gene sets may be used to identify the existence of sub-classes in the data, and thus may allow better understanding of patient stratification. Furthermore, by reducing the observed bias this may allow more direct identification of biologically relevant, and potentially causal, genes. PMID:29470520

Multi-equilibrium property of metabolic networks: SSI module.

PubMed

Lei, Hong-Bo; Zhang, Ji-Feng; Chen, Luonan

2011-06-20

Revealing the multi-equilibrium property of a metabolic network is a fundamental and important topic in systems biology. Due to the complexity of the metabolic network, it is generally a difficult task to study the problem as a whole from both analytical and numerical viewpoint. On the other hand, the structure-oriented modularization idea is a good choice to overcome such a difficulty, i.e. decomposing the network into several basic building blocks and then studying the whole network through investigating the dynamical characteristics of the basic building blocks and their interactions. Single substrate and single product with inhibition (SSI) metabolic module is one type of the basic building blocks of metabolic networks, and its multi-equilibrium property has important influence on that of the whole metabolic networks. In this paper, we describe what the SSI metabolic module is, characterize the rates of the metabolic reactions by Hill kinetics and give a unified model for SSI modules by using a set of nonlinear ordinary differential equations with multi-variables. Specifically, a sufficient and necessary condition is first given to describe the injectivity of a class of nonlinear systems, and then, the sufficient condition is used to study the multi-equilibrium property of SSI modules. As a main theoretical result, for the SSI modules in which each reaction has no more than one inhibitor, a sufficient condition is derived to rule out multiple equilibria, i.e. the Jacobian matrix of its rate function is nonsingular everywhere. In summary, we describe SSI modules and give a general modeling framework based on Hill kinetics, and provide a sufficient condition for ruling out multiple equilibria of a key type of SSI module.

Multi-equilibrium property of metabolic networks: SSI module

PubMed Central

2011-01-01

Background Revealing the multi-equilibrium property of a metabolic network is a fundamental and important topic in systems biology. Due to the complexity of the metabolic network, it is generally a difficult task to study the problem as a whole from both analytical and numerical viewpoint. On the other hand, the structure-oriented modularization idea is a good choice to overcome such a difficulty, i.e. decomposing the network into several basic building blocks and then studying the whole network through investigating the dynamical characteristics of the basic building blocks and their interactions. Single substrate and single product with inhibition (SSI) metabolic module is one type of the basic building blocks of metabolic networks, and its multi-equilibrium property has important influence on that of the whole metabolic networks. Results In this paper, we describe what the SSI metabolic module is, characterize the rates of the metabolic reactions by Hill kinetics and give a unified model for SSI modules by using a set of nonlinear ordinary differential equations with multi-variables. Specifically, a sufficient and necessary condition is first given to describe the injectivity of a class of nonlinear systems, and then, the sufficient condition is used to study the multi-equilibrium property of SSI modules. As a main theoretical result, for the SSI modules in which each reaction has no more than one inhibitor, a sufficient condition is derived to rule out multiple equilibria, i.e. the Jacobian matrix of its rate function is nonsingular everywhere. Conclusions In summary, we describe SSI modules and give a general modeling framework based on Hill kinetics, and provide a sufficient condition for ruling out multiple equilibria of a key type of SSI module. PMID:21689474

Promoting Inquiry-Based Teaching in Laboratory Courses: Are We Meeting the Grade?

PubMed Central

Butler, Amy; Burke da Silva, Karen

2014-01-01

Over the past decade, repeated calls have been made to incorporate more active teaching and learning in undergraduate biology courses. The emphasis on inquiry-based teaching is especially important in laboratory courses, as these are the courses in which students are applying the process of science. To determine the current state of research on inquiry-based teaching in undergraduate biology laboratory courses, we reviewed the recent published literature on inquiry-based exercises. The majority of studies in our data set were in the subdisciplines of biochemistry, cell biology, developmental biology, genetics, and molecular biology. In addition, most exercises were guided inquiry, rather than open ended or research based. Almost 75% of the studies included assessment data, with two-thirds of these studies including multiple types of assessment data. However, few exercises were assessed in multiple courses or at multiple institutions. Furthermore, assessments were rarely based on published instruments. Although the results of the studies in our data set show a positive effect of inquiry-based teaching in biology laboratory courses on student learning gains, research that uses the same instrument across a range of courses and institutions is needed to determine whether these results can be generalized. PMID:25185228

[Stimuli sensitive changes in electrical surface properties of soft membranes: from a synthesized polymer to a biological system].

PubMed

Makino, K

1997-01-01

The electrical surface properties of biological cells have been studied, which provided us with the fundamental knowledge about the cell surface. The change in shape or biological functions of cells may affect the surface properties and can be detected by electrokinetic measurements. Biological cell surfaces are covered with polysaccharide chains, some are charged and some are not. Some polysaccharides produce a hydrogel matrixes under a proper condition. We thus consider it reasonable that cell surface is approximated by a hydrogel surface. Electrophoretic mobility measurements are useful for studying the surface properties of biological cells suspended as colloidal particles in an electrolyte solution. The electro-osmotic velocity measurements on the other hand are advantageous to the study of the surface properties of slab-shaped biological systems such as membranes. This work was started with a hydrogel, as a model material. As a hydrogel, poly(N-isopropylacrylamide) poly(NIPAAm), abbreviated as hereafter, was chosen, because this hydrogel changes its volume depending on temperature. The dependence of the electrophoretic mobility of latex particles covered with poly(NIPAAm) hydrogel layer or of the electro-osmotic mobility on poly(NIPAAm) plate upon temperature and ionic strength of the dispersing medium was well explained with an electrophoretic mobility formula for "soft particles" developed by Ohshima. The electrokinetic measurements and the explanation of data with an electrophoretic mobility formula for "soft particles" give us information about the surface charge density and the "softness" of soft surfaces. On the basis of the findings with hydrogels, we have discussed the relationship between the changes in shape or function of the biological cells and the change in physicochemical surface properties using these measurements. To study the change in physicochemical properties of the cell surface caused by apoptosis, we have measured the electrophoretic mobilities of intact and apoptotic human promyelocytic leukemia cell lines, HL-60RG cells. We have also studied the differences observed in surface properties of malignant lymphosarcoma cell line, RAW117-P, and its variant, RAW117-H10, with a high metastatic property to the liver. In both cases, the cell surfaces became softer by the changes of biological functions. We have applied electrophoresis and electro-osmosis measurements to the study of the electrokinetic surface properties of rat basophilic leukemia cells, RBL cells. It was also found that the surface of Human umbilical vein endothelial cells, HUVEC, is considerably soft as compared with those of other biological cells we have studied before.

Effects of cover crops on soil quality: Selected chemical and biological parameters

USDA-ARS?s Scientific Manuscript database

Cover crops may improve soil physical, chemical, and biological properties and thus help improve land productivity. The objective of this study was to evaluate short-term changes (6, 9, and 12 weeks) in soil chemical and biological properties as influenced by cover crops for two different soils and...

Intellectual property rights, standards and data exchange in systems biology: Reflections from the IP Expert Meeting at the University of Luxembourg, 8-9 October 2015, ERASysAPP - ERA-Net for Systems Biology Applications.

PubMed

van Zimmeren, Esther; Rutz, Berthold; Minssen, Timo

2016-12-01

Intellectual property rights (IPRs) have become a key concern for researchers and industry in basically all high-tech sectors. IPRs regularly figure prominently in scientific journals and at scientific conferences and lead to dedicated workshops to increase the awareness and "IPR savviness" of scientists. In 2015, Biotechnology Journal published a report from an expert meeting on "Synthetic Biology & Intellectual Property Rights" organized by the Danish Agency for Science, Technology and Innovation sponsored by the European Research Area Network (ERA-Net) in Synthetic Biology (ERASynBio), in which we provided a number of recommendations for a variety of stakeholders [1]. The current article offers some deeper reflections about the interface between IPRs, standards and data exchange in systems biology (SysBio) resulting from an Expert Meeting funded by another ERA-Net, ERASysAPP. The meeting brought together experts and stakeholders (e.g. scientists, company representatives, officials from public funding organizations) in SysBio from different European countries. Despite the different profiles of the stakeholders at the meeting and the variety of interests, many concerns and opinions were shared. In case particular views were expressed by a specific type of stakeholder, this will be explicitly mentioned in the text. In this article, we explore a number of particularly relevant issues that were discussed at the meeting and offer some recommendations. SysBio involves the study of biological systems at a so-called systems level. This is not a new concept in the life sciences - many former approaches in physiology, enzymology and other scientific disciplines have already taken a systemic view of selected biological subjects. Yet, SysBio has gained strong interest within the past 10 to 15 years. One predominant reason and a critical prerequisite for this success story being that the relevant scientific methodologies and research tools have become far more powerful and accurate. Remarkable technical progress allows scientists to generate, collect, display and analyse quantitative and qualitative data on biological processes and activities in much greater volumes, velocity, variety and veracity. The skilful integration of multiple heterogeneous data sets allows scientists to model and predict biological processes. SysBio's interdisciplinary nature requires data, models and other research assets to be formatted and described in standard ways to enable exchange and reuse of high quality data [2]. This allows a more effective utilisation of the enormous potential that rests in "big data" analysis. Finally, SysBio is often closely linked to or provides the foundation for Synthetic Biology (SynBio). Standardization and data exchange in SysBio may result in challenges and opportunities related to IPRs. The aim of this article is to raise awareness on these issues within the SysBio scientific community and to stimulate exploration of different strategies for dealing with IPRs in order to optimize access to and use of valuable research results. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Using multi-criteria analysis of simulation models to understand complex biological systems

Treesearch

Maureen C. Kennedy; E. David Ford

2011-01-01

Scientists frequently use computer-simulation models to help solve complex biological problems. Typically, such models are highly integrated, they produce multiple outputs, and standard methods of model analysis are ill suited for evaluating them. We show how multi-criteria optimization with Pareto optimality allows for model outputs to be compared to multiple system...

Practice Makes Pretty Good: Assessment of Primary Literature Reading Abilities across Multiple Large-Enrollment Biology Laboratory Courses

ERIC Educational Resources Information Center

Sato, Brian K.; Kadandale, Pavan; He, Wenliang; Murata, Paige M. N.; Latif, Yama; Warschauer, Mark

2014-01-01

Primary literature is essential for scientific communication and is commonly utilized in undergraduate biology education. Despite this, there is often little time spent "training" our students how to critically analyze a paper. To address this, we introduced a primary literature module in multiple upper-division laboratory courses. In…

Optimization of spatial frequency domain imaging technique for estimating optical properties of food and biological materials

USDA-ARS?s Scientific Manuscript database

Spatial frequency domain imaging technique has recently been developed for determination of the optical properties of food and biological materials. However, accurate estimation of the optical property parameters by the technique is challenging due to measurement errors associated with signal acquis...

Inspiring Integration in College Students Reading Multiple Biology Texts

ERIC Educational Resources Information Center

Firetto, Carla

2013-01-01

Introductory biology courses typically present topics on related biological systems across separate chapters and lectures. A complete foundational understanding requires that students understand how these biological systems are related. Unfortunately, spontaneous generation of these connections is rare for novice learners. These experiments focus…

Functional Module Analysis for Gene Coexpression Networks with Network Integration.

PubMed

Zhang, Shuqin; Zhao, Hongyu; Ng, Michael K

2015-01-01

Network has been a general tool for studying the complex interactions between different genes, proteins, and other small molecules. Module as a fundamental property of many biological networks has been widely studied and many computational methods have been proposed to identify the modules in an individual network. However, in many cases, a single network is insufficient for module analysis due to the noise in the data or the tuning of parameters when building the biological network. The availability of a large amount of biological networks makes network integration study possible. By integrating such networks, more informative modules for some specific disease can be derived from the networks constructed from different tissues, and consistent factors for different diseases can be inferred. In this paper, we have developed an effective method for module identification from multiple networks under different conditions. The problem is formulated as an optimization model, which combines the module identification in each individual network and alignment of the modules from different networks together. An approximation algorithm based on eigenvector computation is proposed. Our method outperforms the existing methods, especially when the underlying modules in multiple networks are different in simulation studies. We also applied our method to two groups of gene coexpression networks for humans, which include one for three different cancers, and one for three tissues from the morbidly obese patients. We identified 13 modules with three complete subgraphs, and 11 modules with two complete subgraphs, respectively. The modules were validated through Gene Ontology enrichment and KEGG pathway enrichment analysis. We also showed that the main functions of most modules for the corresponding disease have been addressed by other researchers, which may provide the theoretical basis for further studying the modules experimentally.

Analysis of selected sugars and sugar phosphates in mouse heart tissue by reductive amination and liquid chromatography-electrospray ionization mass spectrometry.

PubMed

Han, Jun; Tschernutter, Vera; Yang, Juncong; Eckle, Tobias; Borchers, Christoph H

2013-06-18

Sensitive and reliable analysis of sugars and sugar phosphates in tissues and cells is essential for many biological and cell engineering studies. However, the successful analysis of these endogenous compounds in biological samples by liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) is often difficult because of their poor chromatographic retention properties in reversed-phase LC, the complex biological matrices, and the ionization suppression in ESI. This situation is further complicated by the existence of their multiple structural isomers in vivo. This work describes the combination of reductive amination using 3-amino-9-ethylcarbazole, with a new LC approach using a pentafluorophenyl core-shell ultrahigh performance (UP) LC column and methylphosphonic acid as an efficient tail-sweeping reagent for improved chromatographic separation. This new method was used for selected detection and accurate quantitation of the major free and phosphorylated reducing sugars in mouse heart tissue. Among the detected compounds, accurate quantitation of glyceraldehyde, ribose, glucose, glycerylaldehyde-3-phosphate, ribose-5-phosphate, glucose-6-phosphate, and mannose-6-phosphate was achieved by UPLC/multiple-reaction monitoring (MRM)-MS, with analytical accuracies ranging from 87.4% to 109.4% and CVs of ≤8.5% (n = 6). To demonstrate isotope-resolved metabolic profiling, we used UPLC/quadrupole time-of-flight (QTOF)-MS to analyze the isotope distribution patterns of C3 to C6 free and phosphorylated reducing sugars in heart tissues from (13)C-labeled wild type and knockout mice. In conclusion, the preanalytical derivatization-LC/ESI-MS method has resulted in selective determination of free and phosphorylated reducing sugars without the interferences from their nonreducing structural isomers in mouse heart tissue, with analytical sensitivities in the femtomole to low picomole range.

An easy-to-build and re-usable microfluidic system for live-cell imaging.

PubMed

Babic, Julien; Griscom, Laurent; Cramer, Jeremy; Coudreuse, Damien

2018-06-20

Real-time monitoring of cellular responses to dynamic changes in their environment or to specific treatments has become central to cell biology. However, when coupled to live-cell imaging, such strategies are difficult to implement with precision and high time resolution, and the simultaneous alteration of multiple parameters is a major challenge. Recently, microfluidics has provided powerful solutions for such analyses, bringing an unprecedented level of control over the conditions and the medium in which cells under microscopic observation are grown. However, such technologies have remained under-exploited, largely as a result of the complexity associated with microfabrication procedures. In this study, we have developed simple but powerful microfluidic devices dedicated to live-cell imaging. These microsystems take advantage of a robust elastomer that is readily available to researchers and that presents excellent bonding properties, in particular to microscopy-grade glass coverslips. Importantly, the chips are easy-to-build without sophisticated equipment, and they are compatible with the integration of complex, customized fluidic networks as well as with the multiplexing of independent assays on a single device. We show that the chips are re-usable, a significant advantage for the popularization of microfluidics in cell biology. Moreover, we demonstrate that they allow for the dynamic, accurate and simultaneous control of multiple parameters of the cellular environment. While they do not possess all the features of the microdevices that are built using complex and costly procedures, the simplicity and versatility of the chips that we have developed make them an attractive alternative for a range of applications. The emergence of such devices, which can be fabricated and used by any laboratory, will provide the possibility for a larger number of research teams to take full advantage of these new methods for investigating cell biology.

[Industrial exploitation of renewable resources: from ethanol production to bioproducts development].

PubMed

Lopes Ferreira, Nicolas

2008-01-01

Plants, which are one of major groups of life forms, are constituted of an amazing number of molecules such as sugars, proteins, phenolic compounds etc. These molecules display multiple and complementary properties involved in various compartments of plants (structure, storage, biological activity etc.). The first uses of plants in industry were for food and feed, paper manufacturing or combustion. In the coming decades, these renewable biological materials will be the basis of a new concept: the "biorefiner" i.e. the chemical conversion of the whole plant to various products and uses. This concept, born in the 90ies, is analogous to today's petroleum refinery, which produces multiple fuels and derivative products from petroleum. Agriculture generates lots of co-products which were most often wasted. The rational use of these wasted products, which can be considered as valuable renewable materials, is now economically interesting and will contribute to the reduction of greenhouse has emissions by partially substituting for fossil fuels. Such substructures from biological waste products and transforming them into biofuels and new industrial products named "bioproducts". These compounds, such as bioplastics or biosurfactants, can replace equivalent petroleum derivatives. Towards that goal, lots of filamentous fungi, growing on a broad range of vegetable species, are able to produce enzymes adapted to the modification of these type of substrates. The best example, at least the more industrially developed to date, is the second generation biofuel technology using cellulose as a raw material. The process includes an enzymatic hydrolysis step which requires cellulases secreted from Trichoderma fungal species. This industrial development of a renewable energy will contribute to the diversification of energy sources used to transport and to the development of green chemistry which will partially substitute petrochemicals.

Mitsunobu alkylation of cancerostatic 5-fluorouridine with (2E)-10-hydroxydec-2-enoic acid, a fatty acid from royal jelly with multiple biological activities.

PubMed

Ottenhaus, Vanessa; Rosemeyer, Helmut

2015-09-01

5-Fluorouridine (1) - a nucleoside antimetabolite with strong cancerostatic properties - was protected i) at the 2'- and 3'-OH groups with a heptan-4-ylidene residue and ii) at the 5'-OH group with a (4-methoxyphenyl)(diphenyl)methyl residue. This fully protected compound, 3, was submitted to a Mitsunobu reaction with the N-hydroxysuccinimide (NHS) ester, 5, of (2E)-10-hydroxydec-2-enoic acid (4) which gave nucleolipid 6. The latter was detritylated with Cl2 CHCOOH to yield the co-drug 7 as NHS ester. Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.

Stem cells.

PubMed

Behr, Björn; Ko, Sae Hee; Wong, Victor W; Gurtner, Geoffrey C; Longaker, Michael T

2010-10-01

Stem cells are self-renewing cells capable of differentiating into multiple cell lines and are classified according to their origin and their ability to differentiate. Enormous potential exists in use of stem cells for regenerative medicine. To produce effective stem cell-based treatments for a range of diseases, an improved understanding of stem cell biology and better control over stem cell fate are necessary. In addition, the barriers to clinical translation, such as potential oncologic properties of stem cells, need to be addressed. With renewed government support and continued refinement of current stem cell methodologies, the future of stem cell research is exciting and promises to provide novel reconstructive options for patients and surgeons limited by traditional paradigms.

Progress in understanding and overcoming biomass recalcitrance: a BioEnergy Science Center (BESC) perspective

DOE PAGES

Gilna, Paul; Lynd, Lee R.; Mohnen, Debra; ...

2017-11-30

The DOE BioEnergy Science Center has operated as a virtual center with multiple partners for a decade targeting overcoming biomass recalcitrance. BESC has redefined biomass recalcitrance from an observable phenotype to a better understood and manipulatable fundamental and operational property. These manipulations are then the result of deeper biological understanding and can be combined with other advanced biotechnology improvements in biomass conversion to improve bioenergy processes and markets. This article provides an overview of key accomplishments in overcoming recalcitrance via better plants, better microbes, and better tools and combinations. Finally, we present a perspective on the aspects of successful centermore » operation.« less

Progress in understanding and overcoming biomass recalcitrance: a BioEnergy Science Center (BESC) perspective

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

Gilna, Paul; Lynd, Lee R.; Mohnen, Debra

The DOE BioEnergy Science Center has operated as a virtual center with multiple partners for a decade targeting overcoming biomass recalcitrance. BESC has redefined biomass recalcitrance from an observable phenotype to a better understood and manipulatable fundamental and operational property. These manipulations are then the result of deeper biological understanding and can be combined with other advanced biotechnology improvements in biomass conversion to improve bioenergy processes and markets. This article provides an overview of key accomplishments in overcoming recalcitrance via better plants, better microbes, and better tools and combinations. Finally, we present a perspective on the aspects of successful centermore » operation.« less

Multifunctional receptor model for dioxin and related compound toxic action: possible thyroid hormone-responsive effector-linked site.

PubMed Central

McKinney, J D

1989-01-01

Molecular/theoretical modeling studies have revealed that thyroid hormones and toxic chlorinated aromatic hydrocarbons of environmental significance (for which dioxin or TCDD is the prototype) have similar structural properties that could be important in molecular recognition in biochemical systems. These molecular properties include a somewhat rigid, sterically accessible and polarizable aromatic ring and size-limited, hydrophobic lateral substituents, usually contained in opposite adjoining rings of a diphenyl compound. These molecular properties define the primary binding groups thought to be important in molecular recognition of both types of structures in biochemical systems. Similar molecular reactivities are supported by the demonstration of effective specific binding of thyroid hormones and chlorinated aromatic hydrocarbons with four different proteins, enzymes, or receptor preparations that are known or suspected to be involved in the expression of thyroid hormone activity. These binding interactions represent both aromatic-aromatic (stacking) and molecular cleft-type recognition processes. A multiple protein or multifunctional receptor-ligand binding mechanism model is proposed as a way of visualizing the details and possible role of both the stacking and cleft type molecular recognition factors in the expression of biological activity. The model suggests a means by which hormone-responsive effector-linked sites (possible protein-protein-DNA complexes) can maintain highly structurally specific control of hormone action. Finally, the model also provides a theoretical basis for the design and conduct of further biological experimentation on the molecular mechanism(s) of action of toxic chlorinated aromatic hydrocarbons and thyroid hormones. Images FIGURE 3. A FIGURE 3. B FIGURE 3. C FIGURE 3. D PMID:2551666

Why an extended evolutionary synthesis is necessary

PubMed Central

2017-01-01

Since the last major theoretical integration in evolutionary biology—the modern synthesis (MS) of the 1940s—the biosciences have made significant advances. The rise of molecular biology and evolutionary developmental biology, the recognition of ecological development, niche construction and multiple inheritance systems, the ‘-omics’ revolution and the science of systems biology, among other developments, have provided a wealth of new knowledge about the factors responsible for evolutionary change. Some of these results are in agreement with the standard theory and others reveal different properties of the evolutionary process. A renewed and extended theoretical synthesis, advocated by several authors in this issue, aims to unite pertinent concepts that emerge from the novel fields with elements of the standard theory. The resulting theoretical framework differs from the latter in its core logic and predictive capacities. Whereas the MS theory and its various amendments concentrate on genetic and adaptive variation in populations, the extended framework emphasizes the role of constructive processes, ecological interactions and systems dynamics in the evolution of organismal complexity as well as its social and cultural conditions. Single-level and unilinear causation is replaced by multilevel and reciprocal causation. Among other consequences, the extended framework overcomes many of the limitations of traditional gene-centric explanation and entails a revised understanding of the role of natural selection in the evolutionary process. All these features stimulate research into new areas of evolutionary biology. PMID:28839929

Seeking unique and common biological themes in multiple gene lists or datasets: pathway pattern extraction pipeline for pathway-level comparative analysis.

PubMed

Yi, Ming; Mudunuri, Uma; Che, Anney; Stephens, Robert M

2009-06-29

One of the challenges in the analysis of microarray data is to integrate and compare the selected (e.g., differential) gene lists from multiple experiments for common or unique underlying biological themes. A common way to approach this problem is to extract common genes from these gene lists and then subject these genes to enrichment analysis to reveal the underlying biology. However, the capacity of this approach is largely restricted by the limited number of common genes shared by datasets from multiple experiments, which could be caused by the complexity of the biological system itself. We now introduce a new Pathway Pattern Extraction Pipeline (PPEP), which extends the existing WPS application by providing a new pathway-level comparative analysis scheme. To facilitate comparing and correlating results from different studies and sources, PPEP contains new interfaces that allow evaluation of the pathway-level enrichment patterns across multiple gene lists. As an exploratory tool, this analysis pipeline may help reveal the underlying biological themes at both the pathway and gene levels. The analysis scheme provided by PPEP begins with multiple gene lists, which may be derived from different studies in terms of the biological contexts, applied technologies, or methodologies. These lists are then subjected to pathway-level comparative analysis for extraction of pathway-level patterns. This analysis pipeline helps to explore the commonality or uniqueness of these lists at the level of pathways or biological processes from different but relevant biological systems using a combination of statistical enrichment measurements, pathway-level pattern extraction, and graphical display of the relationships of genes and their associated pathways as Gene-Term Association Networks (GTANs) within the WPS platform. As a proof of concept, we have used the new method to analyze many datasets from our collaborators as well as some public microarray datasets. This tool provides a new pathway-level analysis scheme for integrative and comparative analysis of data derived from different but relevant systems. The tool is freely available as a Pathway Pattern Extraction Pipeline implemented in our existing software package WPS, which can be obtained at http://www.abcc.ncifcrf.gov/wps/wps_index.php.

The Relations between Number Property Strategies, Working Memory, and Multiplication in Elementary Students

ERIC Educational Resources Information Center

Liu, Ru-De; Ding, Yi; Gao, Bing-Cheng; Zhang, Dake

2015-01-01

This study aimed to examine the relations among property strategies, working memory, and multiplication tasks with 101 Chinese fourth-grade students. Two multiplication property strategies (associative and distributive) were compared with no strategy and demonstrated differentiated effects on students' accuracy and reaction time. Associative…

Do Sophisticated Epistemic Beliefs Predict Meaningful Learning? Findings from a Structural Equation Model of Undergraduate Biology Learning

ERIC Educational Resources Information Center

Lee, Silvia Wen-Yu; Liang, Jyh-Chong; Tsai, Chin-Chung

2016-01-01

This study investigated the relationships among college students' epistemic beliefs in biology (EBB), conceptions of learning biology (COLB), and strategies of learning biology (SLB). EBB includes four dimensions, namely "multiple-source," "uncertainty," "development," and "justification." COLB is further…

A combined computational-experimental analyses of selected metabolic enzymes in Pseudomonas species.

PubMed

Perumal, Deepak; Lim, Chu Sing; Chow, Vincent T K; Sakharkar, Kishore R; Sakharkar, Meena K

2008-09-10

Comparative genomic analysis has revolutionized our ability to predict the metabolic subsystems that occur in newly sequenced genomes, and to explore the functional roles of the set of genes within each subsystem. These computational predictions can considerably reduce the volume of experimental studies required to assess basic metabolic properties of multiple bacterial species. However, experimental validations are still required to resolve the apparent inconsistencies in the predictions by multiple resources. Here, we present combined computational-experimental analyses on eight completely sequenced Pseudomonas species. Comparative pathway analyses reveal that several pathways within the Pseudomonas species show high plasticity and versatility. Potential bypasses in 11 metabolic pathways were identified. We further confirmed the presence of the enzyme O-acetyl homoserine (thiol) lyase (EC: 2.5.1.49) in P. syringae pv. tomato that revealed inconsistent annotations in KEGG and in the recently published SYSTOMONAS database. These analyses connect and integrate systematic data generation, computational data interpretation, and experimental validation and represent a synergistic and powerful means for conducting biological research.

Gold coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy.

PubMed

McLaughlin, Mark F; Woodward, Jonathan; Boll, Rose A; Wall, Jonathan S; Rondinone, Adam J; Kennel, Stephen J; Mirzadeh, Saed; Robertson, J David

2013-01-01

Targeted radiotherapies maximize cytotoxicty to cancer cells. In vivo α-generator targeted radiotherapies can deliver multiple α particles to a receptor site dramatically amplifying the radiation dose delivered to the target. The major challenge with α-generator radiotherapies is that traditional chelating moieties are unable to sequester the radioactive daughters in the bioconjugate which is critical to minimize toxicity to healthy, non-target tissue. The recoil energy of the (225)Ac daughters following α decay will sever any metal-ligand bond used to form the bioconjugate. This work demonstrates that an engineered multilayered nanoparticle-antibody conjugate can deliver multiple α radiations and contain the decay daughters of (225)Ac while targeting biologically relevant receptors in a female BALB/c mouse model. These multi-shell nanoparticles combine the radiation resistance of lanthanide phosphate to contain (225)Ac and its radioactive decay daughters, the magnetic properties of gadolinium phosphate for easy separation, and established gold chemistry for attachment of targeting moieties.

Scale-dependent intrinsic entropies of complex time series.

PubMed

Yeh, Jia-Rong; Peng, Chung-Kang; Huang, Norden E

2016-04-13

Multi-scale entropy (MSE) was developed as a measure of complexity for complex time series, and it has been applied widely in recent years. The MSE algorithm is based on the assumption that biological systems possess the ability to adapt and function in an ever-changing environment, and these systems need to operate across multiple temporal and spatial scales, such that their complexity is also multi-scale and hierarchical. Here, we present a systematic approach to apply the empirical mode decomposition algorithm, which can detrend time series on various time scales, prior to analysing a signal's complexity by measuring the irregularity of its dynamics on multiple time scales. Simulated time series of fractal Gaussian noise and human heartbeat time series were used to study the performance of this new approach. We show that our method can successfully quantify the fractal properties of the simulated time series and can accurately distinguish modulations in human heartbeat time series in health and disease. © 2016 The Author(s).

A Redox-Nucleophilic Dual-Reactable Probe for Highly Selective and Sensitive Detection of H2S: Synthesis, Spectra and Bioimaging

NASA Astrophysics Data System (ADS)

Zhang, Changyu; Wang, Runyu; Cheng, Longhuai; Li, Bingjie; Xi, Zhen; Yi, Long

2016-07-01

Hydrogen sulfide (H2S) is an important signalling molecule with multiple biological functions. The reported H2S fluorescent probes are majorly based on redox or nucleophilic reactions. The combination usage of both redox and nucleophilic reactions could improve the probe’s selectivity, sensitivity and stability. Herein we report a new dual-reactable probe with yellow turn-on fluorescence for H2S detection. The sensing mechanism of the dual-reactable probe was based on thiolysis of NBD (7-nitro-1,2,3-benzoxadiazole) amine (a nucleophilic reaction) and reduction of azide to amine (a redox reaction). Compared with its corresponding single-reactable probes, the dual-reactable probe has higher selectivity and fluorescence turn-on fold with magnitude of multiplication from that of each single-reactable probe. The highly selective and sensitive properties enabled the dual-reactable probe as a useful tool for efficiently sensing H2S in aqueous buffer and in living cells.

Prediction With Dimension Reduction of Multiple Molecular Data Sources for Patient Survival.

PubMed

Kaplan, Adam; Lock, Eric F

2017-01-01

Predictive modeling from high-dimensional genomic data is often preceded by a dimension reduction step, such as principal component analysis (PCA). However, the application of PCA is not straightforward for multisource data, wherein multiple sources of 'omics data measure different but related biological components. In this article, we use recent advances in the dimension reduction of multisource data for predictive modeling. In particular, we apply exploratory results from Joint and Individual Variation Explained (JIVE), an extension of PCA for multisource data, for prediction of differing response types. We conduct illustrative simulations to illustrate the practical advantages and interpretability of our approach. As an application example, we consider predicting survival for patients with glioblastoma multiforme from 3 data sources measuring messenger RNA expression, microRNA expression, and DNA methylation. We also introduce a method to estimate JIVE scores for new samples that were not used in the initial dimension reduction and study its theoretical properties; this method is implemented in the R package R.JIVE on CRAN, in the function jive.predict.

Revisiting Preschoolers' Living Things Concept: A Microgenetic Analysis of Conceptual Change in Basic Biology

ERIC Educational Resources Information Center

Opfer, John E.; Siegler, Robert S.

2004-01-01

Many preschoolers know that plants and animals share basic biological properties, but this knowledge does not usually lead them to conclude that plants, like animals, are living things. To resolve this seeming paradox, we hypothesized that preschoolers largely base their judgments of life status on a biological property, capacity for teleological…

Fat-soluble vitamins as disease modulators in multiple sclerosis.

PubMed

Torkildsen, Ø; Løken-Amsrud, K I; Wergeland, S; Myhr, K-M; Holmøy, T

2013-01-01

Fat-soluble vitamins (A, D, E and K) have properties that could be relevant as modulators of disease activity in multiple sclerosis (MS). We performed a systematic search on PubMed and Medline up to May 2012, using the search strings 'vitamin A', 'retinol', 'retinal', 'carotenoids', 'vitamin D', 'vitamin E', 'alpha-tocopherol', 'vitamin K' in conjunction with 'multiple sclerosis', 'animal model' and 'experimental autoimmune encephalitis (EAE)'. In addition, the reference lists of the publications identified were examined for further citations of relevance. There is comprehensive evidence from epidemiological, observational, and experimental studies that vitamin D may be beneficial in MS. Results from small-scale clinical studies are inconclusive, and large-scale, adequately powered, randomized, controlled trials are still lacking. For vitamin D, Oxford Centre for Evidence-Based Medicine level 2c evidence exists for a positive therapeutic effect. Evidence from animal models indicates that all the examined fat-soluble vitamins could have potential as modulators of disease activity in MS. For vitamin A and E, level 4 and 5 evidence exists for a modulatory effect in MS; for vitamin K, too few studies have been conducted to indicate an effect in humans. Vitamin D is a promising candidate as modulator of disease activity in MS, and controlled studies are currently being conducted. All the fat-soluble vitamins have, however, been demonstrated to be effective in different animal models for the disease, and vitamin A and E have biological properties that could be relevant for MS pathogenesis. Thus, vitamin A and E seem to be promising candidates for future case-control and cohort studies. © 2012 John Wiley & Sons A/S.

The next step in biology: a periodic table?

PubMed

Dhar, Pawan K

2007-08-01

Systems biology is an approach to explain the behaviour of a system in relation to its individual components. Synthetic biology uses key hierarchical and modular concepts of systems biology to engineer novel biological systems. In my opinion the next step in biology is to use molecule-to-phenotype data using these approaches and integrate them in the form a periodic table. A periodic table in biology would provide chassis to classify, systematize and compare diversity of component properties vis-a-vis system behaviour. Using periodic table it could be possible to compute higher- level interactions from component properties. This paper examines the concept of building a bio-periodic table using protein fold as the fundamental unit.

Multifactorial causal model of brain (dis)organization and therapeutic intervention: Application to Alzheimer's disease.

PubMed

Iturria-Medina, Yasser; Carbonell, Félix M; Sotero, Roberto C; Chouinard-Decorte, Francois; Evans, Alan C

2017-05-15

Generative models focused on multifactorial causal mechanisms in brain disorders are scarce and generally based on limited data. Despite the biological importance of the multiple interacting processes, their effects remain poorly characterized from an integrative analytic perspective. Here, we propose a spatiotemporal multifactorial causal model (MCM) of brain (dis)organization and therapeutic intervention that accounts for local causal interactions, effects propagation via physical brain networks, cognitive alterations, and identification of optimum therapeutic interventions. In this article, we focus on describing the model and applying it at the population-based level for studying late onset Alzheimer's disease (LOAD). By interrelating six different neuroimaging modalities and cognitive measurements, this model accurately predicts spatiotemporal alterations in brain amyloid-β (Aβ) burden, glucose metabolism, vascular flow, resting state functional activity, structural properties, and cognitive integrity. The results suggest that a vascular dysregulation may be the most-likely initial pathologic event leading to LOAD. Nevertheless, they also suggest that LOAD it is not caused by a unique dominant biological factor (e.g. vascular or Aβ) but by the complex interplay among multiple relevant direct interactions. Furthermore, using theoretical control analysis of the identified population-based multifactorial causal network, we show the crucial advantage of using combinatorial over single-target treatments, explain why one-target Aβ based therapies might fail to improve clinical outcomes, and propose an efficiency ranking of possible LOAD interventions. Although still requiring further validation at the individual level, this work presents the first analytic framework for dynamic multifactorial brain (dis)organization that may explain both the pathologic evolution of progressive neurological disorders and operationalize the influence of multiple interventional strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

Stochastic and superharmonic stochastic resonances of a confined overdamped harmonic oscillator

NASA Astrophysics Data System (ADS)

Zhang, Lu; Lai, Li; Peng, Hao; Tu, Zhe; Zhong, Suchuan

2018-01-01

The dynamics of many soft condensed matter and biological systems is affected by space limitations, which produce some peculiar effects on the systems' stochastic resonance (SR) behavior. In this study, we propose a model where SR can be observed: a confined overdamped harmonic oscillator that is subjected to a sinusoidal driving force and is under the influence of a multiplicative white noise. The output response of the system is a periodic signal with harmonic frequencies that are odd multiples of the driving frequency. We verify the amplitude resonances at the driving frequencies and superharmonic frequencies that are equal to three, five, and seven times the driving frequency, using a numerical method based on the stochastic Taylor expansion. The synergistic effect of the multiplicative white noise, constant boundaries, and periodic driving force that can induce a SR in the output amplitude at the driving and superharmonic frequencies is found. The SR phenomenon found in this paper is sensitive to the driving amplitude and frequency, inherent potential parameter, and boundary width, thus leading to various resonance conditions. Therefore, the mechanism found could be beneficial for the characterization of these confined systems and could constitute an important tool for controlling their basic properties.

Fractal Scaling of Particle Size Distribution and Relationships with Topsoil Properties Affected by Biological Soil Crusts

PubMed Central

Gao, Guang-Lei; Ding, Guo-Dong; Wu, Bin; Zhang, Yu-Qing; Qin, Shu-Gao; Zhao, Yuan-Yuan; Bao, Yan-Feng; Liu, Yun-Dong; Wan, Li; Deng, Ji-Feng

2014-01-01

Background Biological soil crusts are common components of desert ecosystem; they cover ground surface and interact with topsoil that contribute to desertification control and degraded land restoration in arid and semiarid regions. Methodology/Principal Findings To distinguish the changes in topsoil affected by biological soil crusts, we compared topsoil properties across three types of successional biological soil crusts (algae, lichens, and mosses crust), as well as the referenced sandland in the Mu Us Desert, Northern China. Relationships between fractal dimensions of soil particle size distribution and selected soil properties were discussed as well. The results indicated that biological soil crusts had significant positive effects on soil physical structure (P<0.05); and soil organic carbon and nutrients showed an upward trend across the successional stages of biological soil crusts. Fractal dimensions ranged from 2.1477 to 2.3032, and significantly linear correlated with selected soil properties (R2 = 0.494∼0.955, P<0.01). Conclusions/Significance Biological soil crusts cause an important increase in soil fertility, and are beneficial to sand fixation, although the process is rather slow. Fractal dimension proves to be a sensitive and useful index for quantifying changes in soil properties that additionally implies desertification. This study will be essential to provide a firm basis for future policy-making on optimal solutions regarding desertification control and assessment, as well as degraded ecosystem restoration in arid and semiarid regions. PMID:24516668

Upper Secondary Students' Understanding of the Use of Multiple Models in Biology Textbooks--The Importance of Conceptual Variation and Incommensurability

ERIC Educational Resources Information Center

Gericke, Niklas; Hagberg, Mariana; Jorde, Doris

2013-01-01

In this study we investigate students' ability to discern conceptual variation and the use of multiple models in genetics when reading content-specific excerpts from biology textbooks. Using the history and philosophy of science as our reference, we were able to develop a research instrument allowing students themselves to investigate the…

Dynamic and rheological properties of soft biological cell suspensions

PubMed Central

Yazdani, Alireza; Li, Xuejin

2016-01-01

Quantifying dynamic and rheological properties of suspensions of soft biological particles such as vesicles, capsules, and red blood cells (RBCs) is fundamentally important in computational biology and biomedical engineering. In this review, recent studies on dynamic and rheological behavior of soft biological cell suspensions by computer simulations are presented, considering both unbounded and confined shear flow. Furthermore, the hemodynamic and hemorheological characteristics of RBCs in diseases such as malaria and sickle cell anemia are highlighted. PMID:27540271

Network-based drug discovery by integrating systems biology and computational technologies

PubMed Central

Leung, Elaine L.; Cao, Zhi-Wei; Jiang, Zhi-Hong; Zhou, Hua

2013-01-01

Network-based intervention has been a trend of curing systemic diseases, but it relies on regimen optimization and valid multi-target actions of the drugs. The complex multi-component nature of medicinal herbs may serve as valuable resources for network-based multi-target drug discovery due to its potential treatment effects by synergy. Recently, robustness of multiple systems biology platforms shows powerful to uncover molecular mechanisms and connections between the drugs and their targeting dynamic network. However, optimization methods of drug combination are insufficient, owning to lacking of tighter integration across multiple ‘-omics’ databases. The newly developed algorithm- or network-based computational models can tightly integrate ‘-omics’ databases and optimize combinational regimens of drug development, which encourage using medicinal herbs to develop into new wave of network-based multi-target drugs. However, challenges on further integration across the databases of medicinal herbs with multiple system biology platforms for multi-target drug optimization remain to the uncertain reliability of individual data sets, width and depth and degree of standardization of herbal medicine. Standardization of the methodology and terminology of multiple system biology and herbal database would facilitate the integration. Enhance public accessible databases and the number of research using system biology platform on herbal medicine would be helpful. Further integration across various ‘-omics’ platforms and computational tools would accelerate development of network-based drug discovery and network medicine. PMID:22877768

Grammatical gender and inferences about biological properties in german-speaking children.

PubMed

Saalbach, Henrik; Imai, Mutsumi; Schalk, Lennart

2012-01-01

In German, nouns are assigned to one of the three gender classes. For most animal names, however, the assignment is independent of the referent's biological sex. We examined whether German-speaking children understand this independence of grammar from semantics or whether they assume that grammatical gender is mapped onto biological sex when drawing inferences about sex-specific biological properties of animals. Two cross-linguistic studies comparing German-speaking and Japanese-speaking preschoolers were conducted. The results suggest that German-speaking children utilize grammatical gender as a cue for inferences about sex-specific properties of animals. Further, we found that Japanese- and German-speaking children recruit different resources when drawing inferences about sex-specific properties: Whereas Japanese children paralleled their pattern of inference about properties common to all animals, German children relied on the grammatical gender class of the animal. Implications of these findings for studying the relation between language and thought are discussed. Copyright © 2012 Cognitive Science Society, Inc.

Functional and evolutionary correlates of gene constellations in the Drosophila melanogaster genome that deviate from the stereotypical gene architecture

PubMed Central

2010-01-01

Background The biological dimensions of genes are manifold. These include genomic properties, (e.g., X/autosomal linkage, recombination) and functional properties (e.g., expression level, tissue specificity). Multiple properties, each generally of subtle influence individually, may affect the evolution of genes or merely be (auto-)correlates. Results of multidimensional analyses may reveal the relative importance of these properties on the evolution of genes, and therefore help evaluate whether these properties should be considered during analyses. While numerous properties are now considered during studies, most work still assumes the stereotypical solitary gene as commonly depicted in textbooks. Here, we investigate the Drosophila melanogaster genome to determine whether deviations from the stereotypical gene architecture correlate with other properties of genes. Results Deviations from the stereotypical gene architecture were classified as the following gene constellations: Overlapping genes were defined as those that overlap in the 5-prime, exonic, or intronic regions. Chromatin co-clustering genes were defined as genes that co-clustered within 20 kb of transcriptional territories. If this scheme is applied the stereotypical gene emerges as a rare occurrence (7.5%), slightly varied schemes yielded between ~1%-50%. Moreover, when following our scheme, paired-overlapping genes and chromatin co-clustering genes accounted for 50.1 and 42.4% of the genes analyzed, respectively. Gene constellation was a correlate of a number of functional and evolutionary properties of genes, but its statistical effect was ~1-2 orders of magnitude lower than the effects of recombination, chromosome linkage and protein function. Analysis of datasets on male reproductive proteins showed these were biased in their representation of gene constellations and evolutionary rate Ka/Ks estimates, but these biases did not overwhelm the biologically meaningful observation of high evolutionary rates of male reproductive genes. Conclusion Given the rarity of the solitary stereotypical gene, and the abundance of gene constellations that deviate from it, the presence of gene constellations, while once thought to be exceptional in large Eukaryote genomes, might have broader relevance to the understanding and study of the genome. However, according to our definition, while gene constellations can be significant correlates of functional properties of genes, they generally are weak correlates of the evolution of genes. Thus, the need for their consideration would depend on the context of studies. PMID:20497561

Behavior of nanoceria in biologically-relevant environments

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

Kumar, Amit; Das, Soumen; Munusamy, Prabhakaran

2014-09-08

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

Use of Graph Database for the Integration of Heterogeneous Biological Data.

PubMed

Yoon, Byoung-Ha; Kim, Seon-Kyu; Kim, Seon-Young

2017-03-01

Understanding complex relationships among heterogeneous biological data is one of the fundamental goals in biology. In most cases, diverse biological data are stored in relational databases, such as MySQL and Oracle, which store data in multiple tables and then infer relationships by multiple-join statements. Recently, a new type of database, called the graph-based database, was developed to natively represent various kinds of complex relationships, and it is widely used among computer science communities and IT industries. Here, we demonstrate the feasibility of using a graph-based database for complex biological relationships by comparing the performance between MySQL and Neo4j, one of the most widely used graph databases. We collected various biological data (protein-protein interaction, drug-target, gene-disease, etc.) from several existing sources, removed duplicate and redundant data, and finally constructed a graph database containing 114,550 nodes and 82,674,321 relationships. When we tested the query execution performance of MySQL versus Neo4j, we found that Neo4j outperformed MySQL in all cases. While Neo4j exhibited a very fast response for various queries, MySQL exhibited latent or unfinished responses for complex queries with multiple-join statements. These results show that using graph-based databases, such as Neo4j, is an efficient way to store complex biological relationships. Moreover, querying a graph database in diverse ways has the potential to reveal novel relationships among heterogeneous biological data.

Use of Graph Database for the Integration of Heterogeneous Biological Data

PubMed Central

Yoon, Byoung-Ha; Kim, Seon-Kyu

2017-01-01

Understanding complex relationships among heterogeneous biological data is one of the fundamental goals in biology. In most cases, diverse biological data are stored in relational databases, such as MySQL and Oracle, which store data in multiple tables and then infer relationships by multiple-join statements. Recently, a new type of database, called the graph-based database, was developed to natively represent various kinds of complex relationships, and it is widely used among computer science communities and IT industries. Here, we demonstrate the feasibility of using a graph-based database for complex biological relationships by comparing the performance between MySQL and Neo4j, one of the most widely used graph databases. We collected various biological data (protein-protein interaction, drug-target, gene-disease, etc.) from several existing sources, removed duplicate and redundant data, and finally constructed a graph database containing 114,550 nodes and 82,674,321 relationships. When we tested the query execution performance of MySQL versus Neo4j, we found that Neo4j outperformed MySQL in all cases. While Neo4j exhibited a very fast response for various queries, MySQL exhibited latent or unfinished responses for complex queries with multiple-join statements. These results show that using graph-based databases, such as Neo4j, is an efficient way to store complex biological relationships. Moreover, querying a graph database in diverse ways has the potential to reveal novel relationships among heterogeneous biological data. PMID:28416946

Bacteriagenic silver nanoparticles: synthesis, mechanism, and applications.

PubMed

Singh, Richa; Shedbalkar, Utkarsha U; Wadhwani, Sweety A; Chopade, Balu A

2015-06-01

Silver nanoparticles (AgNPs) have received tremendous attention due to their significant antimicrobial properties. Large numbers of reports are available on the physical, chemical, and biological syntheses of colloidal AgNPs. Since there is a great need to develop ecofriendly and sustainable methods, biological systems like bacteria, fungi, and plants are being employed to synthesize these nanoparticles. The present review focuses specifically on bacteria-mediated synthesis of AgNPs, its mechanism, and applications. Bacterial synthesis of extra- and intracellular AgNPs has been reported using biomass, supernatant, cell-free extract, and derived components. The extracellular mode of synthesis is preferred over the intracellular mode owing to easy recovery of nanoparticles. Silver-resistant genes, c-type cytochromes, peptides, cellular enzymes like nitrate reductase, and reducing cofactors play significant roles in AgNP synthesis in bacteria. Organic materials released by bacteria act as natural capping and stabilizing agents for AgNPs, thereby preventing their aggregation and providing stability for a longer time. Regulation over reaction conditions has been suggested to control the morphology, dispersion, and yield of nanoparticles. Bacterial AgNPs have anticancer and antioxidant properties. Moreover, the antimicrobial activity of AgNPs in combination with antibiotics signifies their importance in combating the multidrug-resistant pathogenic microorganisms. Multiple microbicidal mechanisms exhibited by AgNPs, depending upon their size and shape, make them very promising as novel nanoantibiotics.

iSS-PC: Identifying Splicing Sites via Physical-Chemical Properties Using Deep Sparse Auto-Encoder.

PubMed

Xu, Zhao-Chun; Wang, Peng; Qiu, Wang-Ren; Xiao, Xuan

2017-08-15

Gene splicing is one of the most significant biological processes in eukaryotic gene expression, such as RNA splicing, which can cause a pre-mRNA to produce one or more mature messenger RNAs containing the coded information with multiple biological functions. Thus, identifying splicing sites in DNA/RNA sequences is significant for both the bio-medical research and the discovery of new drugs. However, it is expensive and time consuming based only on experimental technique, so new computational methods are needed. To identify the splice donor sites and splice acceptor sites accurately and quickly, a deep sparse auto-encoder model with two hidden layers, called iSS-PC, was constructed based on minimum error law, in which we incorporated twelve physical-chemical properties of the dinucleotides within DNA into PseDNC to formulate given sequence samples via a battery of cross-covariance and auto-covariance transformations. In this paper, five-fold cross-validation test results based on the same benchmark data-sets indicated that the new predictor remarkably outperformed the existing prediction methods in this field. Furthermore, it is expected that many other related problems can be also studied by this approach. To implement classification accurately and quickly, an easy-to-use web-server for identifying slicing sites has been established for free access at: http://www.jci-bioinfo.cn/iSS-PC.

Phytochemistry of Cannabis sativa L.

PubMed

ElSohly, Mahmoud A; Radwan, Mohamed M; Gul, Waseem; Chandra, Suman; Galal, Ahmed

Cannabis (Cannabis sativa, or hemp) and its constituents-in particular the cannabinoids-have been the focus of extensive chemical and biological research for almost half a century since the discovery of the chemical structure of its major active constituent, Δ 9 -tetrahydrocannabinol (Δ 9 -THC). The plant's behavioral and psychotropic effects are attributed to its content of this class of compounds, the cannabinoids, primarily Δ 9 -THC, which is produced mainly in the leaves and flower buds of the plant. Besides Δ 9 -THC, there are also non-psychoactive cannabinoids with several medicinal functions, such as cannabidiol (CBD), cannabichromene (CBC), and cannabigerol (CBG), along with other non-cannabinoid constituents belonging to diverse classes of natural products. Today, more than 560 constituents have been identified in cannabis. The recent discoveries of the medicinal properties of cannabis and the cannabinoids in addition to their potential applications in the treatment of a number of serious illnesses, such as glaucoma, depression, neuralgia, multiple sclerosis, Alzheimer's, and alleviation of symptoms of HIV/AIDS and cancer, have given momentum to the quest for further understanding the chemistry, biology, and medicinal properties of this plant.This contribution presents an overview of the botany, cultivation aspects, and the phytochemistry of cannabis and its chemical constituents. Particular emphasis is placed on the newly-identified/isolated compounds. In addition, techniques for isolation of cannabis constituents and analytical methods used for qualitative and quantitative analysis of cannabis and its products are also reviewed.

Immense essence of excellence: marine microbial bioactive compounds.

PubMed

Bhatnagar, Ira; Kim, Se-Kwon

2010-10-15

Oceans have borne most of the biological activities on our planet. A number of biologically active compounds with varying degrees of action, such as anti-tumor, anti-cancer, anti-microtubule, anti-proliferative, cytotoxic, photo protective, as well as antibiotic and antifouling properties, have been isolated to date from marine sources. The marine environment also represents a largely unexplored source for isolation of new microbes (bacteria, fungi, actinomycetes, microalgae-cyanobacteria and diatoms) that are potent producers of bioactive secondary metabolites. Extensive research has been done to unveil the bioactive potential of marine microbes (free living and symbiotic) and the results are amazingly diverse and productive. Some of these bioactive secondary metabolites of microbial origin with strong antibacterial and antifungal activities are being intensely used as antibiotics and may be effective against infectious diseases such as HIV, conditions of multiple bacterial infections (penicillin, cephalosporines, streptomycin, and vancomycin) or neuropsychiatric sequelae. Research is also being conducted on the general aspects of biophysical and biochemical properties, chemical structures and biotechnological applications of the bioactive substances derived from marine microorganisms, and their potential use as cosmeceuticals and nutraceuticals. This review is an attempt to consolidate the latest studies and critical research in this field, and to showcase the immense competence of marine microbial flora as bioactive metabolite producers. In addition, the present review addresses some effective and novel approaches of procuring marine microbial compounds utilizing the latest screening strategies of drug discovery.

Arbuscular mycorrhizal fungal assemblages in biological crusts from a Neotropical savanna are not related to the dominant perennial Trachypogon.

PubMed

Hernández-Hernández, R M; Roldán, A; Caravaca, F; Rodriguez-Caballero, G; Torres, M P; Maestre, F T; Alguacil, M M

2017-01-01

Knowledge of the arbuscular mycorrhizal fungal assemblages in the Trachypogon savanna ecosystems is very important to a better understanding of the ecological processes mediated by this soil microbial group that affects multiple ecosystem functions. Considering the hypothesis that the biocrusts can be linked to vegetation through the arbuscular fungi mycelial network, the objectives proposed in this study were to determine (i) whether there are arbuscular mycorrhizal fungi (AMF) in the biocrusts (ii) whether arbuscular mycorrhizal fungal assemblages are linked to the Trachypogon patches, and (iii) whether the composition of the assemblages is related to soil properties affected by microbiological activity. The community structure of the AMF was investigated in three habitats: rhizospheric soil and roots of Trachypogon vestitus, biological soil crusts, and bare soil. The canonical correspondence analysis showed that two soil properties related to enzymatic activity (protease and β-glucosidase) significantly affected the community composition of the AMF. The biocrusts in the Venezuelan savanna are colonized by an AM fungal community linked to that of the bare soil and significantly different from that hosted by the roots of the surrounding T. vestitus, suggesting that assemblages of AMF in biocrusts might be related more closely to those of annual plant species appearing in favorable conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Immense Essence of Excellence: Marine Microbial Bioactive Compounds

PubMed Central

Bhatnagar, Ira; Kim, Se-Kwon

2010-01-01

Oceans have borne most of the biological activities on our planet. A number of biologically active compounds with varying degrees of action, such as anti-tumor, anti-cancer, anti-microtubule, anti-proliferative, cytotoxic, photo protective, as well as antibiotic and antifouling properties, have been isolated to date from marine sources. The marine environment also represents a largely unexplored source for isolation of new microbes (bacteria, fungi, actinomycetes, microalgae-cyanobacteria and diatoms) that are potent producers of bioactive secondary metabolites. Extensive research has been done to unveil the bioactive potential of marine microbes (free living and symbiotic) and the results are amazingly diverse and productive. Some of these bioactive secondary metabolites of microbial origin with strong antibacterial and antifungal activities are being intensely used as antibiotics and may be effective against infectious diseases such as HIV, conditions of multiple bacterial infections (penicillin, cephalosporines, streptomycin, and vancomycin) or neuropsychiatric sequelae. Research is also being conducted on the general aspects of biophysical and biochemical properties, chemical structures and biotechnological applications of the bioactive substances derived from marine microorganisms, and their potential use as cosmeceuticals and nutraceuticals. This review is an attempt to consolidate the latest studies and critical research in this field, and to showcase the immense competence of marine microbial flora as bioactive metabolite producers. In addition, the present review addresses some effective and novel approaches of procuring marine microbial compounds utilizing the latest screening strategies of drug discovery. PMID:21116414

Conformational properties of serine proteinase inhibitors (serpins) confer multiple pathophysiological roles.

PubMed

Janciauskiene, S

2001-03-26

Serine proteinase inhibitors (Serpins) are irreversible suicide inhibitors of proteases that regulate diverse physiological processes such as coagulation, fibrinolysis, complement activation, angiogenesis, apoptosis, inflammation, neoplasia and viral pathogenesis. The molecular structure and physical properties of serpins permit these proteins to adopt a number of variant conformations under physiological conditions including the native inhibitory form and several inactive, non-inhibitory forms, such as complexes with protease or other ligands, cleaved, polymerised and oxidised. Alterations of a serpin which affect its structure and/or secretion and thus reduce its functional levels may result in pathology. Serpin dysfunction has been implicated in thrombosis, emphysema, liver cirrhosis, immune hypersensitivity and mental disorders. The loss of inhibitory activity of serpins necessarily results in an imbalance between proteases and their inhibitors, but it may also have other physiological effects through the generation of abnormal concentrations of modified, non-inhibitory forms of serpins. Although these forms of inhibitory serpins are detected in tissues and fluids recovered from inflammatory sites, the important questions of which conditions result in generation of different molecular forms of serpins, what biological function these forms have, and which of them are directly linked to pathologies and/or may be useful markers for characterisation of disease states, remain to be answered. Elucidation of the biological activities of non-inhibitory forms of serpins may provide useful insights into the pathogenesis of diseases and suggest new therapeutic strategies.

Designed multiple ligands in metabolic disease research: from concept to platform.

PubMed

Gattrell, W; Johnstone, C; Patel, S; Smith, C Sambrook; Scheel, A; Schindler, M

2013-08-01

Type 2 diabetes mellitus (T2DM) is a multifactorial disease, and drug monotherapy typically results in unsatisfactory treatment outcomes for patients. Even when used in combination, existing therapies lack efficacy in the long term. Designed multiple ligands (DMLs) are compounds developed to modulate multiple targets relevant to a disease. DMLs offer the potential to yield greater efficacy over monotherapies, either by modulating different biological pathways, or by boosting a single one. However, examples of DMLs progressing into clinical trials, or onto the market are rare; DML drug discovery is challenging, and perceived by some to be almost impossible. Nevertheless, with the judicious selection of biological targets, both from a biological and chemical perspective, it is possible to develop drug-like DMLs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Steady states and stability in metabolic networks without regulation.

PubMed

Ivanov, Oleksandr; van der Schaft, Arjan; Weissing, Franz J

2016-07-21

Metabolic networks are often extremely complex. Despite intensive efforts many details of these networks, e.g., exact kinetic rates and parameters of metabolic reactions, are not known, making it difficult to derive their properties. Considerable effort has been made to develop theory about properties of steady states in metabolic networks that are valid for any values of parameters. General results on uniqueness of steady states and their stability have been derived with specific assumptions on reaction kinetics, stoichiometry and network topology. For example, deep results have been obtained under the assumptions of mass-action reaction kinetics, continuous flow stirred tank reactors (CFSTR), concordant reaction networks and others. Nevertheless, a general theory about properties of steady states in metabolic networks is still missing. Here we make a step further in the quest for such a theory. Specifically, we study properties of steady states in metabolic networks with monotonic kinetics in relation to their stoichiometry (simple and general) and the number of metabolites participating in every reaction (single or many). Our approach is based on the investigation of properties of the Jacobian matrix. We show that stoichiometry, network topology, and the number of metabolites that participate in every reaction have a large influence on the number of steady states and their stability in metabolic networks. Specifically, metabolic networks with single-substrate-single-product reactions have disconnected steady states, whereas in metabolic networks with multiple-substrates-multiple-product reactions manifolds of steady states arise. Metabolic networks with simple stoichiometry have either a unique globally asymptotically stable steady state or asymptotically stable manifolds of steady states. In metabolic networks with general stoichiometry the steady states are not always stable and we provide conditions for their stability. In order to demonstrate the biological relevance we illustrate the results on the examples of the TCA cycle, the mevalonate pathway and the Calvin cycle. Copyright © 2016 Elsevier Ltd. All rights reserved.

26 CFR 20.2032A-4 - Method of valuing farm real property.

Code of Federal Regulations, 2011 CFR

2011-04-01

... for property on which buildings or other improvements are located and farms including multiple... property on which comparable buildings or improvements are located must be identified for specially valued property on which buildings or other real property improvements are located. In cases involving multiple...

26 CFR 20.2032A-4 - Method of valuing farm real property.

Code of Federal Regulations, 2010 CFR

2010-04-01

... for property on which buildings or other improvements are located and farms including multiple... property on which comparable buildings or improvements are located must be identified for specially valued property on which buildings or other real property improvements are located. In cases involving multiple...

Effects of imputation on correlation: implications for analysis of mass spectrometry data from multiple biological matrices.

PubMed

Taylor, Sandra L; Ruhaak, L Renee; Kelly, Karen; Weiss, Robert H; Kim, Kyoungmi

2017-03-01

With expanded access to, and decreased costs of, mass spectrometry, investigators are collecting and analyzing multiple biological matrices from the same subject such as serum, plasma, tissue and urine to enhance biomarker discoveries, understanding of disease processes and identification of therapeutic targets. Commonly, each biological matrix is analyzed separately, but multivariate methods such as MANOVAs that combine information from multiple biological matrices are potentially more powerful. However, mass spectrometric data typically contain large amounts of missing values, and imputation is often used to create complete data sets for analysis. The effects of imputation on multiple biological matrix analyses have not been studied. We investigated the effects of seven imputation methods (half minimum substitution, mean substitution, k-nearest neighbors, local least squares regression, Bayesian principal components analysis, singular value decomposition and random forest), on the within-subject correlation of compounds between biological matrices and its consequences on MANOVA results. Through analysis of three real omics data sets and simulation studies, we found the amount of missing data and imputation method to substantially change the between-matrix correlation structure. The magnitude of the correlations was generally reduced in imputed data sets, and this effect increased with the amount of missing data. Significant results from MANOVA testing also were substantially affected. In particular, the number of false positives increased with the level of missing data for all imputation methods. No one imputation method was universally the best, but the simple substitution methods (Half Minimum and Mean) consistently performed poorly. © The Author 2016. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

PROMISE: a tool to identify genomic features with a specific biologically interesting pattern of associations with multiple endpoint variables.

PubMed

Pounds, Stan; Cheng, Cheng; Cao, Xueyuan; Crews, Kristine R; Plunkett, William; Gandhi, Varsha; Rubnitz, Jeffrey; Ribeiro, Raul C; Downing, James R; Lamba, Jatinder

2009-08-15

In some applications, prior biological knowledge can be used to define a specific pattern of association of multiple endpoint variables with a genomic variable that is biologically most interesting. However, to our knowledge, there is no statistical procedure designed to detect specific patterns of association with multiple endpoint variables. Projection onto the most interesting statistical evidence (PROMISE) is proposed as a general procedure to identify genomic variables that exhibit a specific biologically interesting pattern of association with multiple endpoint variables. Biological knowledge of the endpoint variables is used to define a vector that represents the biologically most interesting values for statistics that characterize the associations of the endpoint variables with a genomic variable. A test statistic is defined as the dot-product of the vector of the observed association statistics and the vector of the most interesting values of the association statistics. By definition, this test statistic is proportional to the length of the projection of the observed vector of correlations onto the vector of most interesting associations. Statistical significance is determined via permutation. In simulation studies and an example application, PROMISE shows greater statistical power to identify genes with the interesting pattern of associations than classical multivariate procedures, individual endpoint analyses or listing genes that have the pattern of interest and are significant in more than one individual endpoint analysis. Documented R routines are freely available from www.stjuderesearch.org/depts/biostats and will soon be available as a Bioconductor package from www.bioconductor.org.

New approaches to estimation of peat deposits for production of biologically active compounds

NASA Astrophysics Data System (ADS)

Stepchenko, L. M.; Yurchenko, V. I.; Krasnik, V. G.; Syedykh, N. J.

2009-04-01

It is known, that biologically active preparations from peat increase animals productivity as well as resistance against stress-factors and have adaptogeneous, antioxidant, immunomodulative properties. Optymal choice of peat deposits for the production of biologically active preparations supposes the detailed comparative analysis of peat properties from different deposits. For this the cadastre of peat of Ukraine is developed in the humic substances laboratory named after prof. Khristeva L.A. (Dnipropetrovsk Agrarian University, Ukraine). It based on the research of its physical and chemical properties, toxicity and biological activity, and called Biocadastre. The Biocadastre is based on the set of parameters, including the descriptions of physical and chemical properties (active acidity, degree of decomposition, botanical composition etc.), toxicity estimation (by parabyotyc, infusorial, inhibitor and other tests), biological activity indexes (growth-promoting, antioxidative, adaptogeneous, immunomodulative antistress and other actions). The blocks of Biocadastre indexes are differentiated, taking into account their use for creation the preparations for vegetable, animals and microorganisms. The Biocadastre will allow to choose the peat deposits, most suitable for the production of different biologically active preparations, both wide directed and narrow spectrum of action, depending on application fields (medicine, agriculture, veterinary medicine, microbiological industry, balneology, cosmetology).

Rich in vitamin C or just a convenient snack? Multiple-category reasoning with cross-classified foods.

PubMed

Hayes, Brett K; Kurniawan, Hendy; Newell, Ben R

2011-01-01

Two studies examined multiple category reasoning in property induction with cross-classified foods. Pilot tests identified foods that were more typical of a taxonomic category (e.g., "fruit"; termed 'taxonomic primary') or a script based category (e.g., "snack foods"; termed 'script primary'). They also confirmed that taxonomic categories were perceived as more coherent than script categories. In Experiment 1 participants completed an induction task in which information from multiple categories could be searched and combined to generate a property prediction about a target food. Multiple categories were more often consulted and used in prediction for script primary than for taxonomic primary foods. Experiment 2 replicated this finding across a range of property types but found that multiple category reasoning was reduced in the presence of a concurrent cognitive load. Property type affected which categories were consulted first and how information from multiple categories was weighted. The results show that multiple categories are more likely to be used for property predictions about cross-classified objects when an object is primarily associated with a category that has low coherence.

Computational ligand-based rational design: Role of conformational sampling and force fields in model development.

PubMed

Shim, Jihyun; Mackerell, Alexander D

2011-05-01

A significant number of drug discovery efforts are based on natural products or high throughput screens from which compounds showing potential therapeutic effects are identified without knowledge of the target molecule or its 3D structure. In such cases computational ligand-based drug design (LBDD) can accelerate the drug discovery processes. LBDD is a general approach to elucidate the relationship of a compound's structure and physicochemical attributes to its biological activity. The resulting structure-activity relationship (SAR) may then act as the basis for the prediction of compounds with improved biological attributes. LBDD methods range from pharmacophore models identifying essential features of ligands responsible for their activity, quantitative structure-activity relationships (QSAR) yielding quantitative estimates of activities based on physiochemical properties, and to similarity searching, which explores compounds with similar properties as well as various combinations of the above. A number of recent LBDD approaches involve the use of multiple conformations of the ligands being studied. One of the basic components to generate multiple conformations in LBDD is molecular mechanics (MM), which apply an empirical energy function to relate conformation to energies and forces. The collection of conformations for ligands is then combined with functional data using methods ranging from regression analysis to neural networks, from which the SAR is determined. Accordingly, for effective application of LBDD for SAR determinations it is important that the compounds be accurately modelled such that the appropriate range of conformations accessible to the ligands is identified. Such accurate modelling is largely based on use of the appropriate empirical force field for the molecules being investigated and the approaches used to generate the conformations. The present chapter includes a brief overview of currently used SAR methods in LBDD followed by a more detailed presentation of issues and limitations associated with empirical energy functions and conformational sampling methods.

The Effect of Inkjet Printing over Polymeric Films as Potential Buccal Biologics Delivery Systems.

PubMed

Montenegro-Nicolini, Miguel; Reyes, Patricio E; Jara, Miguel O; Vuddanda, Parameswara R; Neira-Carrillo, Andrónico; Butto, Nicole; Velaga, Sitaram; Morales, Javier O

2018-06-22

The buccal mucosa appears as a promissory route for biologic drug administration, and pharmaceutical films are flexible dosage forms that can be used in the buccal mucosa as drug delivery systems for either a local or systemic effect. Recently, thin films have been used as printing substrates to manufacture these dosage forms by inkjet printing. As such, it is necessary to investigate the effects of printing biologics on films as substrates in terms of their physical and mucoadhesive properties. Here, we explored solvent casting as a conventional method with two biocompatible polymers, hydroxypropyl methylcellulose, and chitosan, and we used electrospinning process as an electrospun film fabrication of polycaprolactone fibers due to its potential to elicit mucoadhesion. Lysozyme was used as biologic drug model and was formulated as a solution for printing by thermal inkjet printing. Films were characterized before and after printing by mechanical and mucoadhesive properties, surface, and ultrastructure morphology through scanning electron microscopy and solid state properties by thermal analysis. Although minor differences were detected in micrographs and thermograms in all polymeric films tested, neither mechanical nor mucoadhesive properties were affected by these differences. Thus, biologic drug printing on films was successful without affecting their mechanical or mucoadhesive properties. These results open way to explore biologics loading on buccal films by inkjet printing, and future efforts will include further in vitro and in vivo evaluations.

NANOSILVER MOVEMENT THROUGH BIOLOGICAL BARRIERS RELATES TO PHYSICOCHEMICAL PROPERTIES

EPA Science Inventory

Linking the physicochemical (PC) properties of engineered nanomaterials (NM) to their biological activity is critical for identifying their (toxic) mode of action, and developing appropriate and effective risk assessment guidelines. Particle surface charge (zeta potential), surfa...

Bottom-up synthetic biology: modular design for making artificial platelets

NASA Astrophysics Data System (ADS)

Majumder, Sagardip; Liu, Allen P.

2018-01-01

Engineering artificial cells to mimic one or multiple fundamental cell biological functions is an emerging area of synthetic biology. Reconstituting functional modules from biological components in vitro is a challenging yet an important essence of bottom-up synthetic biology. Here we describe the concept of building artificial platelets using bottom-up synthetic biology and the four functional modules that together could enable such an ambitious effort.

Physicochemical characterization of silver nanoparticles synthesize using Aloe Vera (Aloe barbadensis)

NASA Astrophysics Data System (ADS)

Kuponiyi, Abiola; Kassama, Lamin; Kukhtareva, Tatiana

2014-08-01

Production of silver nanoparticles (AgNPs) using different biological methods is gaining recognition due to their multiple applications. Although, several physical and chemical methods have been used for the synthesis and stabilizing of AgNPs, yet, a green chemistry method is preferable because it is cost effective and environmentally friendly. The synthesis was done using Aloe Vera (AV) extract because it has chemical compounds such as "Antrokinon" that are known for its antibacterial, antivirus and anticancer properties. We hypothesize that AV extract can produce a stable nanoparticles within the 100 nm range and be biologically active. The biological compounds were extracted from AV skin with water and ethanol which was used as the reduction agent for the synthesis of nanoparticles. The biological extract and AgNO3 were blended and heated to synthesize AgNPs. The reaction process was monitored using UV-Visible spectroscopy. Fourier Transfer Infrared spectroscopy (FTIR) was used for the characterization of biological compounds and their substituent groups before and after the reaction process. Dynamic Light scattering (DLS) method was used to characterize particle size of AgNPs and their biomolecular stability. Results showed that biological compounds such as aliphatic amines, alkenes (=C-H), alkanes (C-H), alcohol (O-H) and unsaturated esters(C-O), which has an average particle size of 109 and 215.8 nm and polydispersity index of 0.451 and 0.375 for ethanol and water extract, respectively. According to TEM measurements the size of AgNPs are in the range 5-20 nm The results suggested that ethanol derived AgNPs contained higher yield of organic compounds, thus has better solubility power than water. Ag NPs can be used to control salmonella in poultry industry.

Scaling in cognitive performance reflects multiplicative multifractal cascade dynamics

PubMed Central

Stephen, Damian G.; Anastas, Jason R.; Dixon, James A.

2012-01-01

Self-organized criticality purports to build multi-scaled structures out of local interactions. Evidence of scaling in various domains of biology may be more generally understood to reflect multiplicative interactions weaving together many disparate scales. The self-similarity of power-law scaling entails homogeneity: fluctuations distribute themselves similarly across many spatial and temporal scales. However, this apparent homogeneity can be misleading, especially as it spans more scales. Reducing biological processes to one power-law relationship neglects rich cascade dynamics. We review recent research into multifractality in executive-function cognitive tasks and propose that scaling reflects not criticality but instead interactions across multiple scales and among fluctuations of multiple sizes. PMID:22529819

Bioinspired ion-transport properties of solid-state single nanochannels and their applications in sensing.

PubMed

Tian, Ye; Wen, Liping; Hou, Xu; Hou, Guanglei; Jiang, Lei

2012-07-16

Biological ion channels are able to control ion-transport processes precisely because of their intriguing properties, such as selectivity, rectification, and gating. Learning from nature, scientists have developed a promising system--solid-state single nanochannels--to mimic biological ion-transport properties. These nanochannels have many impressive properties, such as excess surface charge, making them selective; the ability to be produced or modified asymmetrically, endowing them with rectification; and chemical reactivity of the inner surface, imparting them with desired gating properties. Based on these unique characteristics, solid-state single nanochannels have been explored in various applications, such as sensing. In this context, we summarize recent developments of bioinspired solid-state single nanochannels with ion-transport properties that resemble their biological counterparts, including selectivity, rectification, and gating; their applications in sensing are also introduced briefly. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantum Dots for Live Cell and In Vivo Imaging

PubMed Central

Walling, Maureen A; Novak, Jennifer A; Shepard, Jason R. E

2009-01-01

In the past few decades, technology has made immeasurable strides to enable visualization, identification, and quantitation in biological systems. Many of these technological advancements are occurring on the nanometer scale, where multiple scientific disciplines are combining to create new materials with enhanced properties. The integration of inorganic synthetic methods with a size reduction to the nano-scale has lead to the creation of a new class of optical reporters, called quantum dots. These semiconductor quantum dot nanocrystals have emerged as an alternative to organic dyes and fluorescent proteins, and are brighter and more stable against photobleaching than standard fluorescent indicators. Quantum dots have tunable optical properties that have proved useful in a wide range of applications from multiplexed analysis such as DNA detection and cell sorting and tracking, to most recently demonstrating promise for in vivo imaging and diagnostics. This review provides an in-depth discussion of past, present, and future trends in quantum dot use with an emphasis on in vivo imaging and its related applications. PMID:19333416

Electrospray Ionization Mass Spectrometry: A Technique to Access the Information beyond the Molecular Weight of the Analyte

PubMed Central

Banerjee, Shibdas; Mazumdar, Shyamalava

2012-01-01

The Electrospray Ionization (ESI) is a soft ionization technique extensively used for production of gas phase ions (without fragmentation) of thermally labile large supramolecules. In the present review we have described the development of Electrospray Ionization mass spectrometry (ESI-MS) during the last 25 years in the study of various properties of different types of biological molecules. There have been extensive studies on the mechanism of formation of charged gaseous species by the ESI. Several groups have investigated the origin and implications of the multiple charge states of proteins observed in the ESI-mass spectra of the proteins. The charged analytes produced by ESI can be fragmented by activating them in the gas-phase, and thus tandem mass spectrometry has been developed, which provides very important insights on the structural properties of the molecule. The review will highlight recent developments and emerging directions in this fascinating area of research. PMID:22611397

Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog?

PubMed Central

2017-01-01

Abstract The clinical application of the fetal membranes dates back to nearly a century. Their use has ranged from superficial skin dressings to surgical wound closure. The applications of the fetal membranes are constantly evolving, and key to this is the uncovering of multiple populations of stem and stem‐like cells, each with unique properties that can be exploited for regenerative medicine. In addition to pro‐angiogenic and immunomodulatory properties of the stem and stem‐like cells arising from the fetal membranes, the dehydrated and/or decellularized forms of the fetal membranes have been used to support the growth and function of other cells and tissues, including adipose‐derived mesenchymal stem cells. This concise review explores the biological origin of the fetal membranes, a history of their use in medicine, and recent developments in the use of fetal membranes and their derived stem and stem‐like cells in regenerative medicine. Stem Cells Translational Medicine 2017;6:1767–1776 PMID:28834402

Reduced-fat foods: the complex science of developing diet-based strategies for tackling overweight and obesity.

PubMed

McClements, David J

2015-05-01

Fat plays multiple roles in determining the desirable physicochemical properties, sensory attributes, nutritional profile, and biologic response of food products. Overconsumption of fats is linked to chronic diseases, such as obesity, coronary heart disease, diabetes, and cancer. There is therefore a need to develop reduced-fat products with physicochemical properties and sensory profiles that match those of their full-fat counterparts. In addition, foods may be redesigned to increase the feelings of satiety and satiation, and thereby reduce overall food intake. The successful design of these types of functional foods requires a good understanding of the numerous roles that fat plays in determining food attributes and the development of effective strategies to replace these attributes. This article provides an overview of the current understanding of the influence of fat on the physicochemical and physiologic attributes of emulsion-based food products and highlights approaches to create high-quality foods with reduced-fat contents. © 2015 American Society for Nutrition.

The adsorption of fungal ice-nucleating proteins on mineral dusts: a terrestrial reservoir of atmospheric ice-nucleating particles

NASA Astrophysics Data System (ADS)

O'Sullivan, Daniel; Murray, Benjamin J.; Ross, James F.; Webb, Michael E.

2016-06-01

The occurrence of ice-nucleating particles (INPs) in our atmosphere has a profound impact on the properties and lifetime of supercooled clouds. To date, the identities, sources and abundances of particles capable of nucleating ice at relatively low supercoolings (T > -15 °C) remain enigmatic. While biomolecules such as proteins and carbohydrates have been implicated as important high-temperature INPs, the lack of knowledge on the environmental fates of these species makes it difficult to assess their potential atmospheric impacts. Here we show that such nanoscale ice-nucleating proteins from a common soil-borne fungus (Fusarium avenaceum) preferentially bind to and confer their ice-nucleating properties to kaolinite. The ice-nucleating activity of the proteinaceous INPs is unaffected by adsorption to the clay, and once bound the proteins do not readily desorb, retaining much of the activity even after multiple washings with pure water. The atmospheric implications of the finding that biological residues can confer their ice-nucleating ability to dust particles are discussed.

Design of activated serine-containing catalytic triads with atomic level accuracy

PubMed Central

Rajagopalan, Sridharan; Wang, Chu; Yu, Kai; Kuzin, Alexandre P.; Richter, Florian; Lew, Scott; Miklos, Aleksandr E.; Matthews, Megan L.; Seetharaman, Jayaraman; Su, Min; Hunt, John. F.; Cravatt, Benjamin F.; Baker, David

2014-01-01

A challenge in the computational design of enzymes is that multiple properties must be simultaneously optimized -- substrate-binding, transition state stabilization, and product release -- and this has limited the absolute activity of successful designs. Here, we focus on a single critical property of many enzymes: the nucleophilicity of an active site residue that initiates catalysis. We design proteins with idealized serine-containing catalytic triads, and assess their nucleophilicity directly in native biological systems using activity-based organophosphate probes. Crystal structures of the most successful designs show unprecedented agreement with computational models, including extensive hydrogen bonding networks between the catalytic triad (or quartet) residues, and mutagenesis experiments demonstrate that these networks are critical for serine activation and organophosphate-reactivity. Following optimization by yeast-display, the designs react with organophosphate probes at rates comparable to natural serine hydrolases. Co-crystal structures with diisopropyl fluorophosphate bound to the serine nucleophile suggest the designs could provide the basis for a new class of organophosphate captures agents. PMID:24705591

Potential applications of biphosphonates in dental surgical implants.

PubMed

Berardi, D; Carlesi, T; Rossi, F; Calderini, M; Volpi, R; Perfetti, G

2007-01-01

Biphosphonates are largely used for their unquestionable properties of inhibiting bone resorption by osteoclasts in the treatment of various osteometabolic illnesses such as osteoporosis, multiple myeloma, tumors which metastasize to the bone and malignant hypercalcemia. In this literature review the physico-chemical properties, biologic activities and the mechanisms of action of biphosphonates are described. The use of these drugs is discussed, analyzing the quantity of results which have emerged through in vitro and in vivo experiments on animal models. In this study the efficiency of these drugs is demonstrated in contrasting the osteolitic processes of the alveolar bone, in promoting the neoformation and in bettering the quality of bone implants. However, it is important to draw attention to a worrying correlation which has emerged during the last 3-4 years, between osteonecrosis of the jaw (ONJ) and the systemic administration of aminobiphosphonates. This collateral effect did not emerge following the use of non-aminobiphosphonates. The aim of this review is to identify the guidelines for the use of biphosphonates in oral implant surgery.

Inhibition-Based Biomarkers for Autism Spectrum Disorder.

PubMed

Levin, April R; Nelson, Charles A

2015-07-01

Autism spectrum disorder (ASD) is a behaviorally defined and heterogeneous disorder. Biomarkers for ASD offer the opportunity to improve prediction, diagnosis, stratification by severity and subtype, monitoring over time and in response to interventions, and overall understanding of the underlying biology of this disorder. A variety of potential biomarkers, from the level of genes and proteins to network-level interactions, is currently being examined. Many of these biomarkers relate to inhibition, which is of particular interest because in many cases ASD is thought to be a disorder of imbalance between excitation and inhibition. Abnormalities in inhibition at the cellular level lead to emergent properties in networks of neurons. These properties take into account a more complete genetic and cellular background than findings at the level of individual genes or cells, and are able to be measured in live humans, offering additional potential as diagnostic biomarkers and predictors of behaviors. In this review we provide examples of how altered inhibition may inform the search for ASD biomarkers at multiple levels, from genes to cells to networks.

Molecular Mechanisms Underlying Anti-Inflammatory Actions of 6-(Methylsulfinyl)hexyl Isothiocyanate Derived from Wasabi (Wasabia japonica)

PubMed Central

Uto, Takuhiro; Hou, De-Xing; Morinaga, Osamu; Shoyama, Yukihiro

2012-01-01

6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in wasabi (Wasabia japonica), which is a typical Japanese pungent spice. Recently, in vivo and in vitro studies demonstrated that 6-MSITC has several biological properties, including anti-inflammatory, antimicrobial, antiplatelet, and anticancer effects. We previously reported that 6-MSITC strongly suppresses cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and cytokines, which are important factors that mediate inflammatory processes. Moreover, molecular analysis demonstrated that 6-MSITC blocks the expressions of these factors by suppressing multiple signal transduction pathways to attenuate the activation of transcriptional factors. Structure-activity relationships of 6-MSITC and its analogues containing an isothiocyanate group revealed that methylsulfinyl group and the length of alkyl chain of 6-MSITC might be related to high inhibitory potency. In this paper, we review the anti-inflammatory properties of 6-MSITC and discuss potential molecular mechanisms focusing on inflammatory responses by macrophages. PMID:22927840

Molecular Mechanisms Underlying Anti-Inflammatory Actions of 6-(Methylsulfinyl)hexyl Isothiocyanate Derived from Wasabi (Wasabia japonica).

PubMed

Uto, Takuhiro; Hou, De-Xing; Morinaga, Osamu; Shoyama, Yukihiro

2012-01-01

6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in wasabi (Wasabia japonica), which is a typical Japanese pungent spice. Recently, in vivo and in vitro studies demonstrated that 6-MSITC has several biological properties, including anti-inflammatory, antimicrobial, antiplatelet, and anticancer effects. We previously reported that 6-MSITC strongly suppresses cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and cytokines, which are important factors that mediate inflammatory processes. Moreover, molecular analysis demonstrated that 6-MSITC blocks the expressions of these factors by suppressing multiple signal transduction pathways to attenuate the activation of transcriptional factors. Structure-activity relationships of 6-MSITC and its analogues containing an isothiocyanate group revealed that methylsulfinyl group and the length of alkyl chain of 6-MSITC might be related to high inhibitory potency. In this paper, we review the anti-inflammatory properties of 6-MSITC and discuss potential molecular mechanisms focusing on inflammatory responses by macrophages.

Reduced-Fat Foods: The Complex Science of Developing Diet-Based Strategies for Tackling Overweight and Obesity1234

PubMed Central

McClements, David J

2015-01-01

Fat plays multiple roles in determining the desirable physicochemical properties, sensory attributes, nutritional profile, and biologic response of food products. Overconsumption of fats is linked to chronic diseases, such as obesity, coronary heart disease, diabetes, and cancer. There is therefore a need to develop reduced-fat products with physicochemical properties and sensory profiles that match those of their full-fat counterparts. In addition, foods may be redesigned to increase the feelings of satiety and satiation, and thereby reduce overall food intake. The successful design of these types of functional foods requires a good understanding of the numerous roles that fat plays in determining food attributes and the development of effective strategies to replace these attributes. This article provides an overview of the current understanding of the influence of fat on the physicochemical and physiologic attributes of emulsion-based food products and highlights approaches to create high-quality foods with reduced-fat contents. PMID:25979507

Recent Advances in the Application of Vitamin E TPGS for Drug Delivery

PubMed Central

Yang, Conglian; Wu, Tingting; Qi, Yan; Zhang, Zhiping

2018-01-01

D-ɑ-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) has been approved by FDA as a safe adjuvant and widely used in drug delivery systems. The biological and physicochemical properties of TPGS provide multiple advantages for its applications in drug delivery like high biocompatibility, enhancement of drug solubility, improvement of drug permeation and selective antitumor activity. Notably, TPGS can inhibit the activity of ATP dependent P-glycoprotein and act as a potent excipient for overcoming multi-drug resistance (MDR) in tumor. In this review, we aim to discuss the recent advances of TPGS in drug delivery including TPGS based prodrugs, nitric oxide donor and polymers, and unmodified TPGS based formulations. These potential applications are focused on enhancing delivery efficiency as well as the therapeutic effect of agents, especially on overcoming MDR of tumors. It also demonstrates that the clinical translation of TPGS based nanomedicines is still faced with many challenges, which requires more detailed study on TPGS properties and based delivery system in the future. PMID:29290821

Field data sets for seagrass biophysical properties for the Eastern Banks, Moreton Bay, Australia, 2004-2014

NASA Astrophysics Data System (ADS)

Roelfsema, Chris M.; Kovacs, Eva M.; Phinn, Stuart R.

2015-08-01

This paper describes seagrass species and percentage cover point-based field data sets derived from georeferenced photo transects. Annually or biannually over a ten year period (2004-2014) data sets were collected using 30-50 transects, 500-800 m in length distributed across a 142 km2 shallow, clear water seagrass habitat, the Eastern Banks, Moreton Bay, Australia. Each of the eight data sets include seagrass property information derived from approximately 3000 georeferenced, downward looking photographs captured at 2-4 m intervals along the transects. Photographs were manually interpreted to estimate seagrass species composition and percentage cover (Coral Point Count excel; CPCe). Understanding seagrass biology, ecology and dynamics for scientific and management purposes requires point-based data on species composition and cover. This data set, and the methods used to derive it are a globally unique example for seagrass ecological applications. It provides the basis for multiple further studies at this site, regional to global comparative studies, and, for the design of similar monitoring programs elsewhere.

Properties of branching exponential flights in bounded domains

NASA Astrophysics Data System (ADS)

Zoia, A.; Dumonteil, E.; Mazzolo, A.

2012-11-01

In a series of recent works, important results have been reported concerning the statistical properties of exponential flights evolving in bounded domains, a widely adopted model for finite-speed transport phenomena (Blanco S. and Fournier R., Europhys. Lett., 61 (2003) 168; Mazzolo A., Europhys. Lett., 68 (2004) 350; Bénichou O. et al., Europhys. Lett., 70 (2005) 42). Motivated by physical and biological systems where random spatial displacements are coupled with Galton-Watson birth-death mechanisms, such as neutron multiplication, diffusion of reproducing bacteria or spread of epidemics, in this letter we extend those results in two directions, via a Feynman-Kac formalism. First, we characterize the occupation statistics of exponential flights in the presence of absorption and branching, and give explicit moment formulas for the total length travelled by the walker and the number of performed collisions in a given domain. Then, we show that the survival and escape probability can be derived as well by resorting to a similar approach.

Monocarbonyl Curcumin Analogs: Heterocyclic Pleiotropic Kinase Inhibitors that Mediate Anti-Cancer Properties

PubMed Central

Brown, Andrew; Shi, Qi; Moore, Terry W.; Yoon, Younghyoun; Prussia, Andrew; Maddox, Clinton; Liotta, Dennis C.; Shim*, Hyunsuk; Snyder*, James P.

2014-01-01

Curcumin is a biologically active component of curry powder. A structurally-related class of mimetics possesses similar anti-inflammatory and anticancer properties. Mechanism has been examined by exploring kinase inhibition trends. In a screen of 50 kinases relevant to many forms of cancer, one member of the series (4, EF31) showed ≥85% inhibition for ten of the enzymes at 5 μM, while twenty-two of the proteins were blocked at ≥40%. IC50’s for an expanded set of curcumin analogs established a rank order of potencies, and analyses of IKKβ and AKT2 enzyme kinetics for 4 revealed a mixed inhibition model, ATP competition dominating. Our curcumin mimetics are generally selective for Ser/Thr kinases. Both selectivity and potency trends are compatible with protein sequence comparisons, while modeled kinase binding site geometries deliver a reasonable correlation with mixed inhibition. Overall, these analogs are shown to be pleiotropic inhibitors that operate at multiple points along cell signaling pathways. PMID:23550937

Monocarbonyl curcumin analogues: heterocyclic pleiotropic kinase inhibitors that mediate anticancer properties.

PubMed

Brown, Andrew; Shi, Qi; Moore, Terry W; Yoon, Younghyoun; Prussia, Andrew; Maddox, Clinton; Liotta, Dennis C; Shim, Hyunsuk; Snyder, James P

2013-05-09

Curcumin is a biologically active component of curry powder. A structurally related class of mimetics possesses similar anti-inflammatory and anticancer properties. Mechanism has been examined by exploring kinase inhibition trends. In a screen of 50 kinases relevant to many forms of cancer, one member of the series (4, EF31) showed ≥85% inhibition for 10 of the enzymes at 5 μM, while 22 of the proteins were blocked at ≥40%. IC50 values for an expanded set of curcumin analogues established a rank order of potencies, and analyses of IKKβ and AKT2 enzyme kinetics for 4 revealed a mixed inhibition model, ATP competition dominating. Our curcumin mimetics are generally selective for Ser/Thr kinases. Both selectivity and potency trends are compatible with protein sequence comparisons, while modeled kinase binding site geometries deliver a reasonable correlation with mixed inhibition. Overall, these analogues are shown to be pleiotropic inhibitors that operate at multiple points along cell signaling pathways.

Characterisation of minimalist co-assembled fluorenylmethyloxycarbonyl self-assembling peptide systems for presentation of multiple bioactive peptides.

PubMed

Horgan, Conor C; Rodriguez, Alexandra L; Li, Rui; Bruggeman, Kiara F; Stupka, Nicole; Raynes, Jared K; Day, Li; White, John W; Williams, Richard J; Nisbet, David R

2016-07-01

The nanofibrillar structures that underpin self-assembling peptide (SAP) hydrogels offer great potential for the development of finely tuned cellular microenvironments suitable for tissue engineering. However, biofunctionalisation without disruption of the assembly remains a key issue. SAPS present the peptide sequence within their structure, and studies to date have typically focused on including a single biological motif, resulting in chemically and biologically homogenous scaffolds. This limits the utility of these systems, as they cannot effectively mimic the complexity of the multicomponent extracellular matrix (ECM). In this work, we demonstrate the first successful co-assembly of two biologically active SAPs to form a coassembled scaffold of distinct two-component nanofibrils, and demonstrate that this approach is more bioactive than either of the individual systems alone. Here, we use two bioinspired SAPs from two key ECM proteins: Fmoc-FRGDF containing the RGD sequence from fibronectin and Fmoc-DIKVAV containing the IKVAV sequence from laminin. Our results demonstrate that these SAPs are able to co-assemble to form stable hybrid nanofibres containing dual epitopes. Comparison of the co-assembled SAP system to the individual SAP hydrogels and to a mixed system (composed of the two hydrogels mixed together post-assembly) demonstrates its superior stable, transparent, shear-thinning hydrogels at biological pH, ideal characteristics for tissue engineering applications. Importantly, we show that only the coassembled hydrogel is able to induce in vitro multinucleate myotube formation with C2C12 cells. This work illustrates the importance of tissue engineering scaffold functionalisation and the need to develop increasingly advanced multicomponent systems for effective ECM mimicry. Successful control of stem cell fate in tissue engineering applications requires the use of sophisticated scaffolds that deliver biological signals to guide growth and differentiation. The complexity of such processes necessitates the presentation of multiple signals in order to effectively mimic the native extracellular matrix (ECM). Here, we establish the use of two biofunctional, minimalist self-assembling peptides (SAPs) to construct the first co-assembled SAP scaffold. Our work characterises this construct, demonstrating that the physical, chemical, and biological properties of the peptides are maintained during the co-assembly process. Importantly, the coassembled system demonstrates superior biological performance relative to the individual SAPs, highlighting the importance of complex ECM mimicry. This work has important implications for future tissue engineering studies. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Bringing life to soil physical processes

NASA Astrophysics Data System (ADS)

Hallett, P. D.

2013-12-01

When Oklahoma's native prairie grass roots were replaced by corn, the greatest environmental (and social) disaster ever to hit America ensued. The soils lost structure, physical binding by roots was annihilated and when drought came the Great Dust Bowl commenced. This form of environmental disaster has repeated over history and although not always apparent, similar processes drive the degradation of seemingly productive farmland and forests. But just as negative impacts on biology are deleterious to soil physical properties, positive impacts could reverse these trends. In finding solutions to soil sustainability and food security, we should be able to exploit biological processes to improve soil physical properties. This talk will focus on a quantitative understanding of how biology changes soil physical behaviour. Like the Great Dust Bowl, it starts with reinforcement mechanisms by plant roots. We found that binding of soil by cereal (barley) roots within 5 weeks of planting can more than double soil shear strength, with greater plant density causing greater reinforcement. With time, however, the relative impact of root reinforcement diminishes due to root turnover and aging of the seedbed. From mechanical tests of individual roots, reasonable predictions of reinforcement by tree roots are possible with fibre bundle models. With herbaceous plants like cereals, however, the same parameters (root strength, stiffness, size and distribution) result in a poor prediction. We found that root type, root age and abiotic factors such as compaction and waterlogging affect mechanical behaviour, further complicating the understanding and prediction of root reinforcement. For soil physical stability, the interface between root and soil is an extremely important zone in terms of resistance of roots to pull-out and rhizosphere formation. Compounds analogous to root exudates have been found with rheological tests to initially decrease the shear stress where wet soils flow, but after decomposition of these exudates by microbes the shear stress increases. This suggests an initial dispersion, followed by aggregation of the soil, which explains the structural arrangement of soil particles in the rhizosphere observed by microscopy. Dispersion of soil minerals in the root zone is important to release bound nutrients from mineral surfaces. Using fracture mechanics we measured large impacts of biological exudates on the toughness and interparticle bond energy of soils. Now novel tests are being developed to quantify interparticle bonding by biological exudates on single and multiple particle contacts, including mechanical test specimens that can be inoculated with specific bacteria or fungi. This will allow for clay mineralogy, water potential and solution chemistry impacts on interparticle bonding to be quantified directly. Wettability experiments with the same samples measure hydrological properties such as contact angle. Basic information from these tests will help explain biological processes that drive soil structure formation and stabilisation, providing data for models of soil structure dynamics.

Acellular assessments of engineered-manufactured nanoparticle biological surface reactivity

EPA Science Inventory

It is critical to assess the surface properties and reactivity of engineered-manufactured nanoparticles (NPs) as these will influence their interactions with biological systems, biokinetics and toxicity. We examined the physicochemical properties and surface reactivity of metal o...

Mechanical properties of biological specimens explored by atomic force microscopy

NASA Astrophysics Data System (ADS)

Kasas, S.; Longo, G.; Dietler, G.

2013-04-01

The atomic force microscope is a widely used surface scanning apparatus capable of reconstructing at a nanometric scale resolution the 3D morphology of biological samples. Due to its unique sensitivity, it is now increasingly used as a force sensor, to characterize the mechanical properties of specimens with a similar lateral resolution. This unique capability has produced, in the last years, a vast increase in the number of groups that have exploited the versatility and sensitivity of the instrument to explore the nanomechanics of various samples in the fields of biology, microbiology and medicine. In this review we outline the state of the art in this field, reporting the most interesting recent works involving the exploration of the nanomechanical properties of various biological samples.

Study on the Antimicrobial Properties of Citrate-Based Biodegradable Polymers

PubMed Central

Su, Lee-Chun; Xie, Zhiwei; Zhang, Yi; Nguyen, Kytai Truong; Yang, Jian

2014-01-01

Citrate-based polymers possess unique advantages for various biomedical applications since citric acid is a natural metabolism product, which is biocompatible and antimicrobial. In polymer synthesis, citric acid also provides multiple functional groups to control the crosslinking of polymers and active binding sites for further conjugation of biomolecules. Our group recently developed a number of citrate-based polymers for various biomedical applications by taking advantage of their controllable chemical, mechanical, and biological characteristics. In this study, various citric acid derived biodegradable polymers were synthesized and investigated for their physicochemical and antimicrobial properties. Results indicate that citric acid derived polymers reduced bacterial proliferation to different degrees based on their chemical composition. Among the studied polymers, poly(octamethylene citrate) showed ~70–80% suppression to microbe proliferation, owing to its relatively higher ratio of citric acid contents. Crosslinked urethane-doped polyester elastomers and biodegradable photoluminescent polymers also exhibited significant bacteria reduction of ~20 and ~50% for Staphylococcus aureus and Escherichia coli, respectively. Thus, the intrinsic antibacterial properties in citrate-based polymers enable them to inhibit bacteria growth without incorporation of antibiotics, silver nanoparticles, and other traditional bacteria-killing agents suggesting that the citrate-based polymers are unique beneficial materials for wound dressing, tissue engineering, and other potential medical applications where antimicrobial property is desired. PMID:25023605

Mucin gel assembly is controlled by a collective action of non-mucin proteins, disulfide bridges, Ca2+-mediated links, and hydrogen bonding.

PubMed

Meldrum, Oliver W; Yakubov, Gleb E; Bonilla, Mauricio R; Deshmukh, Omkar; McGuckin, Michael A; Gidley, Michael J

2018-04-11

Mucus is characterized by multiple levels of assembly at different length scales which result in a unique set of rheological (flow) and mechanical properties. These physical properties determine its biological function as a highly selective barrier for transport of water and nutrients, while blocking penetration of pathogens and foreign particles. Altered integrity of the mucus layer in the small intestine has been associated with a number of gastrointestinal tract pathologies such as Crohn's disease and cystic fibrosis. In this work, we uncover an intricate hierarchy of intestinal mucin (Muc2) assembly and show how complex rheological properties emerge from synergistic interactions between mucin glycoproteins, non-mucin proteins, and Ca 2+ . Using a novel method of mucus purification, we demonstrate the mechanism of assembly of Muc2 oligomers into viscoelastic microscale domains formed via hydrogen bonding and Ca 2+ -mediated links, which require the joint presence of Ca 2+ ions and non-mucin proteins. These microscale domains aggregate to form a heterogeneous yield stress gel-like fluid, the macroscopic rheological properties of which are virtually identical to that of native intestinal mucus. Through proteomic analysis, we short-list potential protein candidates implicated in mucin assembly, thus paving the way for identifying the molecules responsible for the physiologically critical biophysical properties of mucus.

Anisotropic polyvinyl alcohol hydrogel phantom for shear wave elastography in fibrous biological soft tissue: a multimodality characterization

NASA Astrophysics Data System (ADS)

Chatelin, Simon; Bernal, Miguel; Deffieux, Thomas; Papadacci, Clément; Flaud, Patrice; Nahas, Amir; Boccara, Claude; Gennisson, Jean-Luc; Tanter, Mickael; Pernot, Mathieu

2014-11-01

Shear wave elastography imaging techniques provide quantitative measurement of soft tissues elastic properties. Tendons, muscles and cerebral tissues are composed of fibers, which induce a strong anisotropic effect on the mechanical behavior. Currently, these tissues cannot be accurately represented by existing elastography phantoms. Recently, a novel approach for orthotropic hydrogel mimicking soft tissues has been developed (Millon et al 2006 J. Biomed. Mater. Res. B 305-11). The mechanical anisotropy is induced in a polyvinyl alcohol (PVA) cryogel by stretching the physical crosslinks of the polymeric chains while undergoing freeze/thaw cycles. In the present study we propose an original multimodality imaging characterization of this new transverse isotropic (TI) PVA hydrogel. Multiple properties were investigated using a large variety of techniques at different scales compared with an isotropic PVA hydrogel undergoing similar imaging and rheology protocols. The anisotropic mechanical (dynamic and static) properties were studied using supersonic shear wave imaging technique, full-field optical coherence tomography (FFOCT) strain imaging and classical linear rheometry using dynamic mechanical analysis. The anisotropic optical and ultrasonic spatial coherence properties were measured by FFOCT volumetric imaging and backscatter tensor imaging, respectively. Correlation of mechanical and optical properties demonstrates the complementarity of these techniques for the study of anisotropy on a multi-scale range as well as the potential of this TI phantom as fibrous tissue-mimicking phantom for shear wave elastographic applications.

Diversified Control Paths: A Significant Way Disease Genes Perturb the Human Regulatory Network

PubMed Central

Wang, Bingbo; Gao, Lin; Zhang, Qingfang; Li, Aimin; Deng, Yue; Guo, Xingli

2015-01-01

Background The complexity of biological systems motivates us to use the underlying networks to provide deep understanding of disease etiology and the human diseases are viewed as perturbations of dynamic properties of networks. Control theory that deals with dynamic systems has been successfully used to capture systems-level knowledge in large amount of quantitative biological interactions. But from the perspective of system control, the ways by which multiple genetic factors jointly perturb a disease phenotype still remain. Results In this work, we combine tools from control theory and network science to address the diversified control paths in complex networks. Then the ways by which the disease genes perturb biological systems are identified and quantified by the control paths in a human regulatory network. Furthermore, as an application, prioritization of candidate genes is presented by use of control path analysis and gene ontology annotation for definition of similarities. We use leave-one-out cross-validation to evaluate the ability of finding the gene-disease relationship. Results have shown compatible performance with previous sophisticated works, especially in directed systems. Conclusions Our results inspire a deeper understanding of molecular mechanisms that drive pathological processes. Diversified control paths offer a basis for integrated intervention techniques which will ultimately lead to the development of novel therapeutic strategies. PMID:26284649

The cornerstone K-RAS mutation in pancreatic adenocarcinoma: From cell signaling network, target genes, biological processes to therapeutic targeting.

PubMed

Jonckheere, Nicolas; Vasseur, Romain; Van Seuningen, Isabelle

2017-03-01

RAS belongs to the super family of small G proteins and plays crucial roles in signal transduction from membrane receptors in the cell. Mutations of K-RAS oncogene lead to an accumulation of GTP-bound proteins that maintains an active conformation. In the pancreatic ductal adenocarcinoma (PDAC), one of the most deadly cancers in occidental countries, mutations of the K-RAS oncogene are nearly systematic (>90%). Moreover, K-RAS mutation is the earliest genetic alteration occurring during pancreatic carcinogenetic sequence. In this review, we discuss the central role of K-RAS mutations and their tremendous diversity of biological properties by the interconnected regulation of signaling pathways (MAPKs, NF-κB, PI3K, Ral…). In pancreatic ductal adenocarcinoma, transcriptome analysis and preclinical animal models showed that K-RAS mutation alters biological behavior of PDAC cells (promoting proliferation, migration and invasion, evading growth suppressors, regulating mucin pattern, and miRNA expression). K-RAS also impacts tumor microenvironment and PDAC metabolism reprogramming. Finally we discuss therapeutic targeting strategies of K-RAS that have been developed without significant clinical success so far. As K-RAS is considered as the undruggable target, targeting its multiple effectors and target genes should be considered as potential alternatives. Copyright © 2017 Elsevier B.V. All rights reserved.

Detecting gene subnetworks under selection in biological pathways.

PubMed

Gouy, Alexandre; Daub, Joséphine T; Excoffier, Laurent

2017-09-19

Advances in high throughput sequencing technologies have created a gap between data production and functional data analysis. Indeed, phenotypes result from interactions between numerous genes, but traditional methods treat loci independently, missing important knowledge brought by network-level emerging properties. Therefore, detecting selection acting on multiple genes affecting the evolution of complex traits remains challenging. In this context, gene network analysis provides a powerful framework to study the evolution of adaptive traits and facilitates the interpretation of genome-wide data. We developed a method to analyse gene networks that is suitable to evidence polygenic selection. The general idea is to search biological pathways for subnetworks of genes that directly interact with each other and that present unusual evolutionary features. Subnetwork search is a typical combinatorial optimization problem that we solve using a simulated annealing approach. We have applied our methodology to find signals of adaptation to high-altitude in human populations. We show that this adaptation has a clear polygenic basis and is influenced by many genetic components. Our approach, implemented in the R package signet, improves on gene-level classical tests for selection by identifying both new candidate genes and new biological processes involved in adaptation to altitude. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Challenges and dreams: physics of weak interactions essential to life.

PubMed

Chien, Peter; Gierasch, Lila M

2014-11-05

Biological systems display stunning capacities to self-organize. Moreover, their subcellular architectures are dynamic and responsive to changing needs and conditions. Key to these properties are manifold weak "quinary" interactions that have evolved to create specific spatial networks of macromolecules. These specific arrangements of molecules enable signals to be propagated over distances much greater than molecular dimensions, create phase separations that define functional regions in cells, and amplify cellular responses to changes in their environments. A major challenge is to develop biochemical tools and physical models to describe the panoply of weak interactions operating in cells. We also need better approaches to measure the biases in the spatial distributions of cellular macromolecules that result from the integrated action of multiple weak interactions. Partnerships between cell biologists, biochemists, and physicists are required to deploy these methods. Together these approaches will help us realize the dream of understanding the biological "glue" that sustains life at a molecular and cellular level. © 2014 Chien and Gierasch. 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).

Estimation, modeling, and simulation of patterned growth in extreme environments.

PubMed

Strader, B; Schubert, K E; Quintana, M; Gomez, E; Curnutt, J; Boston, P

2011-01-01

In the search for life on Mars and other extraterrestrial bodies or in our attempts to identify biological traces in the most ancient rock record of Earth, one of the biggest problems facing us is how to recognize life or the remains of ancient life in a context very different from our planet's modern biological examples. Specific chemistries or biological properties may well be inapplicable to extraterrestrial conditions or ancient Earth environments. Thus, we need to develop an arsenal of techniques that are of broader applicability. The notion of patterning created in some fashion by biological processes and properties may provide such a generalized property of biological systems no matter what the incidentals of chemistry or environmental conditions. One approach to recognizing these kinds of patterns is to look at apparently organized arrangements created and left by life in extreme environments here on Earth, especially at various spatial scales, different geologies, and biogeochemical circumstances.

Differential Network Analysis Reveals Evolutionary Complexity in Secondary Metabolism of Rauvolfia serpentina over Catharanthus roseus

PubMed Central

Pathania, Shivalika; Bagler, Ganesh; Ahuja, Paramvir S.

2016-01-01

Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Toward these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These genes may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of R. serpentina, and key genes that contribute toward diversification of specific metabolites. PMID:27588023

Differential Network Analysis Reveals Evolutionary Complexity in Secondary Metabolism of Rauvolfia serpentina over Catharanthus roseus.

PubMed

Pathania, Shivalika; Bagler, Ganesh; Ahuja, Paramvir S

2016-01-01

Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Toward these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These genes may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of R. serpentina, and key genes that contribute toward diversification of specific metabolites.

Skin and scales of teleost fish: Simple structure but high performance and multiple functions

NASA Astrophysics Data System (ADS)

Vernerey, Franck J.; Barthelat, Francois

2014-08-01

Natural and man-made structural materials perform similar functions such as structural support or protection. Therefore they rely on the same types of properties: strength, robustness, lightweight. Nature can therefore provide a significant source of inspiration for new and alternative engineering designs. We report here some results regarding a very common, yet largely unknown, type of biological material: fish skin. Within a thin, flexible and lightweight layer, fish skins display a variety of strain stiffening and stabilizing mechanisms which promote multiple functions such as protection, robustness and swimming efficiency. We particularly discuss four important features pertaining to scaled skins: (a) a strongly elastic tensile behavior that is independent from the presence of rigid scales, (b) a compressive response that prevents buckling and wrinkling instabilities, which are usually predominant for thin membranes, (c) a bending response that displays nonlinear stiffening mechanisms arising from geometric constraints between neighboring scales and (d) a robust structure that preserves the above characteristics upon the loss or damage of structural elements. These important properties make fish skin an attractive model for the development of very thin and flexible armors and protective layers, especially when combined with the high penetration resistance of individual scales. Scaled structures inspired by fish skin could find applications in ultra-light and flexible armor systems, flexible electronics or the design of smart and adaptive morphing structures for aerospace vehicles.

Engineering of Microbial Cell Factories for the Production of Plant Polyphenols with Health-Beneficial Properties.

PubMed

Dudnik, Alexey; Gaspar, Paula; Neves, Ana Rute; Forster, Jochen

2018-05-15

Polyphenols form a group of important natural bioactive compounds with numerous ascribed health-beneficial attributes (e.g. antioxidant, anti-inflammatory, anti-microbial and tumor-suppressing properties). Some polyphenols can also be used as natural dyes or plastic precursors. Notwithstanding their relevance, production of most of these compounds still relies on extraction from plant material, which for most of it is a costly and an inefficient procedure. The use of microbial cell factories for this purpose is an emerging alternative that could allow a more efficient and sustainable production. The most recent advances in molecular biology and genetic engineering, combined with the ever-growing understanding of microbial physiology have led to multiple success stories. Production of multiple polyphenolic compounds or their direct precursors has been achieved not only in the common production hosts, such as Escherichia coli and Saccharomyces cerevisiae but also in Corynebacterium glutamicum and Lactococcus lactis. However, boosting production of native compounds or introduction of heterologous biosynthetic pathways also brings certain challenges, such as the need to express, balance and maintain efficient precursor supply. This review will discuss the most recent advances in the field of metabolic engineering of microorganisms for polyphenol biosynthesis and its future perspectives, as well as outlines their potential health benefits and current production methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Deep Learning Applications for Predicting Pharmacological Properties of Drugs and Drug Repurposing Using Transcriptomic Data.

PubMed

Aliper, Alexander; Plis, Sergey; Artemov, Artem; Ulloa, Alvaro; Mamoshina, Polina; Zhavoronkov, Alex

2016-07-05

Deep learning is rapidly advancing many areas of science and technology with multiple success stories in image, text, voice and video recognition, robotics, and autonomous driving. In this paper we demonstrate how deep neural networks (DNN) trained on large transcriptional response data sets can classify various drugs to therapeutic categories solely based on their transcriptional profiles. We used the perturbation samples of 678 drugs across A549, MCF-7, and PC-3 cell lines from the LINCS Project and linked those to 12 therapeutic use categories derived from MeSH. To train the DNN, we utilized both gene level transcriptomic data and transcriptomic data processed using a pathway activation scoring algorithm, for a pooled data set of samples perturbed with different concentrations of the drug for 6 and 24 hours. In both pathway and gene level classification, DNN achieved high classification accuracy and convincingly outperformed the support vector machine (SVM) model on every multiclass classification problem, however, models based on pathway level data performed significantly better. For the first time we demonstrate a deep learning neural net trained on transcriptomic data to recognize pharmacological properties of multiple drugs across different biological systems and conditions. We also propose using deep neural net confusion matrices for drug repositioning. This work is a proof of principle for applying deep learning to drug discovery and development.

Deep learning applications for predicting pharmacological properties of drugs and drug repurposing using transcriptomic data

PubMed Central

Aliper, Alexander; Plis, Sergey; Artemov, Artem; Ulloa, Alvaro; Mamoshina, Polina; Zhavoronkov, Alex

2016-01-01

Deep learning is rapidly advancing many areas of science and technology with multiple success stories in image, text, voice and video recognition, robotics and autonomous driving. In this paper we demonstrate how deep neural networks (DNN) trained on large transcriptional response data sets can classify various drugs to therapeutic categories solely based on their transcriptional profiles. We used the perturbation samples of 678 drugs across A549, MCF‐7 and PC‐3 cell lines from the LINCS project and linked those to 12 therapeutic use categories derived from MeSH. To train the DNN, we utilized both gene level transcriptomic data and transcriptomic data processed using a pathway activation scoring algorithm, for a pooled dataset of samples perturbed with different concentrations of the drug for 6 and 24 hours. In both gene and pathway level classification, DNN convincingly outperformed support vector machine (SVM) model on every multiclass classification problem, however, models based on a pathway level classification perform better. For the first time we demonstrate a deep learning neural net trained on transcriptomic data to recognize pharmacological properties of multiple drugs across different biological systems and conditions. We also propose using deep neural net confusion matrices for drug repositioning. This work is a proof of principle for applying deep learning to drug discovery and development. PMID:27200455

Clique Relaxations in Biological and Social Network Analysis Foundations and Algorithms

DTIC Science & Technology

2015-10-26

study of clique relaxation models arising in biological and social networks. This project examines the elementary clique-defining properties... elementary clique-defining properties inherently exploited in the available clique relaxation models and pro- poses a taxonomic framework that not...analyzes the elementary clique-defining properties implicitly exploited in the available clique relaxation models and proposes a taxonomic framework that

Optical properties of dissolved organic matter (DOM): Effects of biological and photolytic degradation

USGS Publications Warehouse

Hansen, Angela; Kraus, Tamara; Pellerin, Brian; Fleck, Jacob; Downing, Bryan D.; Bergamaschi, Brian

2016-01-01

Advances in spectroscopic techniques have led to an increase in the use of optical properties (absorbance and fluorescence) to assess dissolved organic matter (DOM) composition and infer sources and processing. However, little information is available to assess the impact of biological and photolytic processing on the optical properties of original DOM source materials. We measured changes in commonly used optical properties and indices in DOM leached from peat soil, plants, and algae following biological and photochemical degradation to determine whether they provide unique signatures that can be linked to original DOM source. Changes in individual optical parameters varied by source material and process, with biodegradation and photodegradation often causing values to shift in opposite directions. Although values for different source materials overlapped at the end of the 111-day lab experiment, multivariate statistical analyses showed that unique optical signatures could be linked to original DOM source material even after degradation, with 17 optical properties determined by discriminant analysis to be significant (p<0.05) in distinguishing between DOM source and environmental processing. These results demonstrate that inferring the source material from optical properties is possible when parameters are evaluated in combination even after extensive biological and photochemical alteration.

Predictive Models of Nanotoxicity: Relationship of Physicochemical Properties to Particle Movement Through Biological Barriers

EPA Science Inventory

Understanding the linkage between the physicochemical (PC) properties of nanoparticles (NP) and their activation of biological systems is poorly understood, yet fundamental to predicting nanotoxicity, idenitifying mode of actions and developing appropriate and effective regul...

Promoting inquiry-based teaching in laboratory courses: are we meeting the grade?

PubMed

Beck, Christopher; Butler, Amy; da Silva, Karen Burke

2014-01-01

Over the past decade, repeated calls have been made to incorporate more active teaching and learning in undergraduate biology courses. The emphasis on inquiry-based teaching is especially important in laboratory courses, as these are the courses in which students are applying the process of science. To determine the current state of research on inquiry-based teaching in undergraduate biology laboratory courses, we reviewed the recent published literature on inquiry-based exercises. The majority of studies in our data set were in the subdisciplines of biochemistry, cell biology, developmental biology, genetics, and molecular biology. In addition, most exercises were guided inquiry, rather than open ended or research based. Almost 75% of the studies included assessment data, with two-thirds of these studies including multiple types of assessment data. However, few exercises were assessed in multiple courses or at multiple institutions. Furthermore, assessments were rarely based on published instruments. Although the results of the studies in our data set show a positive effect of inquiry-based teaching in biology laboratory courses on student learning gains, research that uses the same instrument across a range of courses and institutions is needed to determine whether these results can be generalized. © 2014 C. Beck et al. CBE—Life Sciences Education © 2014 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).

Photo-Responsive Graphene and Carbon Nanotubes to Control and Tackle Biological Systems.

PubMed

Cardano, Francesca; Frasconi, Marco; Giordani, Silvia

2018-01-01

Photo-responsive multifunctional nanomaterials are receiving considerable attention for biological applications because of their unique properties. The functionalization of the surface of carbon nanotubes (CNTs) and graphene, among other carbon based nanomaterials, with molecular switches that exhibit reversible transformations between two or more isomers in response to different kind of external stimuli, such as electromagnetic radiation, temperature and pH, has allowed the control of the optical and electrical properties of the nanomaterial. Light-controlled molecular switches, such as azobenzene and spiropyran, have attracted a lot of attention for nanomaterial's functionalization because of the remote modulation of their physicochemical properties using light stimulus. The enhanced properties of the hybrid materials obtained from the coupling of carbon based nanomaterials with light-responsive switches has enabled the fabrication of smart devices for various biological applications, including drug delivery, bioimaging and nanobiosensors. In this review, we highlight the properties of photo-responsive carbon nanomaterials obtained by the conjugation of CNTs and graphene with azobenzenes and spiropyrans molecules to investigate biological systems, devising possible future directions in the field.

Photo-Responsive Graphene and Carbon Nanotubes to Control and Tackle Biological Systems

PubMed Central

Cardano, Francesca; Frasconi, Marco; Giordani, Silvia

2018-01-01

Photo-responsive multifunctional nanomaterials are receiving considerable attention for biological applications because of their unique properties. The functionalization of the surface of carbon nanotubes (CNTs) and graphene, among other carbon based nanomaterials, with molecular switches that exhibit reversible transformations between two or more isomers in response to different kind of external stimuli, such as electromagnetic radiation, temperature and pH, has allowed the control of the optical and electrical properties of the nanomaterial. Light-controlled molecular switches, such as azobenzene and spiropyran, have attracted a lot of attention for nanomaterial's functionalization because of the remote modulation of their physicochemical properties using light stimulus. The enhanced properties of the hybrid materials obtained from the coupling of carbon based nanomaterials with light-responsive switches has enabled the fabrication of smart devices for various biological applications, including drug delivery, bioimaging and nanobiosensors. In this review, we highlight the properties of photo-responsive carbon nanomaterials obtained by the conjugation of CNTs and graphene with azobenzenes and spiropyrans molecules to investigate biological systems, devising possible future directions in the field. PMID:29707534

Photo-Responsive Graphene and Carbon Nanotubes to Control and Tackle Biological Systems

NASA Astrophysics Data System (ADS)

Cardano, Francesca; Frasconi, Marco; Giordani, Silvia

2018-04-01

Photo-responsive multifunctional nanomaterials are receiving considerable attention for biological applications because of their unique properties. The functionalization of the surface of carbon nanotubes (CNTs) and graphene, among other carbon based nanomaterials, with molecular switches that exhibit reversible transformations between two or more isomers in response to different kind of external stimuli, such as electromagnetic radiation, temperature and pH, has allowed the control of the optical and electrical properties of the nanomaterial. Light-controlled molecular switches, such as azobenzene and spiropyran, have attracted a lot of attention for nanomaterial’s functionalization because of the remote modulation of their physicochemical properties using light stimulus. The enhanced properties of the hybrid materials obtained from the coupling of carbon based nanomaterials with light-responsive switches has enabled the fabrication of smart devices for various biological applications, including drug delivery, bioimaging and nanobiosensors. In this review, we highlight the properties of photo-responsive carbon nanomaterials obtained by the conjugation of CNTs and graphene with azobenzenes and spiropyrans molecules to investigate biological systems, devising possible future directions in the field.

Adaption of Ulva pertusa to multiple-contamination of heavy metals and nutrients: Biological mechanism of outbreak of Ulva sp. green tide.

PubMed

Ge, Changzi; Yu, Xiru; Kan, Manman; Qu, Chunfeng

2017-12-15

The multiple-contamination of heavy metals and nutrients worsens increasingly and Ulva sp. green tide occurs almost simultaneously. To reveal the biological mechanism for outbreak of the green tide, Ulva pertusa was exposed to seven-day-multiple-contamination. The relation between pH variation (V pH ), Chl a content, ratio of (Chl a content)/(Chl b content) (R chla/chlb ), SOD activity of U. pertusa (A SOD ) and contamination concentration is [Formula: see text] (p<0.05), C chla =0.88 ±0.09 -0.01 ±0.00 ×C Cd (p<0.05), [Formula: see text] (p<0.05), and [Formula: see text] (p<0.05), respectively. C ammonia , C Cd and C Zn is concentration of ammonia, Cd 2+ and Zn 2+ , respectively. Comparing the contamination concentrations of seawaters where Ulva sp. green tide occurred and the contamination concentrations set in the present work, U. pertusa can adapt to multiple-contaminations in these waters. Thus, the adaption to multiple-contamination may be one biological mechanism for the outbreak of Ulva sp. green tide. Copyright © 2017 Elsevier Ltd. All rights reserved.

Detection of multiple perturbations in multi-omics biological networks.

PubMed

Griffin, Paula J; Zhang, Yuqing; Johnson, William Evan; Kolaczyk, Eric D

2018-05-17

Cellular mechanism-of-action is of fundamental concern in many biological studies. It is of particular interest for identifying the cause of disease and learning the way in which treatments act against disease. However, pinpointing such mechanisms is difficult, due to the fact that small perturbations to the cell can have wide-ranging downstream effects. Given a snapshot of cellular activity, it can be challenging to tell where a disturbance originated. The presence of an ever-greater variety of high-throughput biological data offers an opportunity to examine cellular behavior from multiple angles, but also presents the statistical challenge of how to effectively analyze data from multiple sources. In this setting, we propose a method for mechanism-of-action inference by extending network filtering to multi-attribute data. We first estimate a joint Gaussian graphical model across multiple data types using penalized regression and filter for network effects. We then apply a set of likelihood ratio tests to identify the most likely site of the original perturbation. In addition, we propose a conditional testing procedure to allow for detection of multiple perturbations. We demonstrate this methodology on paired gene expression and methylation data from The Cancer Genome Atlas (TCGA). © 2018, The International Biometric Society.

Miniaturized soft bio-hybrid robotics: a step forward into healthcare applications.

PubMed

Patino, T; Mestre, R; Sánchez, S

2016-10-07

Soft robotics is an emerging discipline that employs soft flexible materials such as fluids, gels and elastomers in order to enhance the use of robotics in healthcare applications. Compared to their rigid counterparts, soft robotic systems have flexible and rheological properties that are closely related to biological systems, thus allowing the development of adaptive and flexible interactions with complex dynamic environments. With new technologies arising in bioengineering, the integration of living cells into soft robotic systems offers the possibility of accomplishing multiple complex functions such as sensing and actuating upon external stimuli. These emerging bio-hybrid systems are showing promising outcomes and opening up new avenues in the field of soft robotics for applications in healthcare and other fields.

A Potential Alternative against Neurodegenerative Diseases: Phytodrugs

PubMed Central

Pérez-Hernández, Jesús; Zaldívar-Machorro, Víctor Javier; Villanueva-Porras, David; Vega-Ávila, Elisa; Chavarría, Anahí

2016-01-01

Neurodegenerative diseases (ND) primarily affect the neurons in the human brain secondary to oxidative stress and neuroinflammation. ND are more common and have a disproportionate impact on countries with longer life expectancies and represent the fourth highest source of overall disease burden in the high-income countries. A large majority of the medicinal plant compounds, such as polyphenols, alkaloids, and terpenes, have therapeutic properties. Polyphenols are the most common active compounds in herbs and vegetables consumed by man. The biological bioactivity of polyphenols against neurodegeneration is mainly due to its antioxidant, anti-inflammatory, and antiamyloidogenic effects. Multiple scientific studies support the use of herbal medicine in the treatment of ND; however, relevant aspects are still pending to explore such as metabolic analysis, pharmacokinetics, and brain bioavailability. PMID:26881043

Design and Elaboration of a Tractable Tricyclic Scaffold To Synthesize Druglike Inhibitors of Dipeptidyl Peptidase-4 (DPP-4), Antagonists of the C-C Chemokine Receptor Type 5 (CCR5), and Highly Potent and Selective Phosphoinositol-3 Kinase δ (PI3Kδ) Inhibitors.

PubMed

Schwehm, Carolin; Kellam, Barrie; Garces, Aimie E; Hill, Stephen J; Kindon, Nicholas D; Bradshaw, Tracey D; Li, Jin; Macdonald, Simon J F; Rowedder, James E; Stoddart, Leigh A; Stocks, Michael J

2017-02-23

A novel molecular scaffold has been synthesized, and its incorporation into new analogues of biologically active molecules across multiple target classes will be discussed. In these studies, we have shown use of the tricyclic scaffold to synthesize potent inhibitors of the serine peptidase DPP-4, antagonists of the CCR5 receptor, and highly potent and selective PI3K δ isoform inhibitors. We also describe the predicted physicochemical properties of the resulting inhibitors and conclude that the tractable molecular scaffold could have potential application in future drug discovery programs.

Appalachian spring: variations on ancient gastro-entero-pancreatic themes in New World mammals.

PubMed

Seino, S; Blackstone, C D; Chan, S J; Whittaker, J; Bell, G I; Steiner, D F

1988-07-01

Studies of guinea pig genomic and/or cDNA clones encoding the gastro-entero-pancreatic (GEP) hormones--insulin, glucagon and pancreatic polypeptide--as well as portions of the insulin receptor, are described. Multiple clustered substitutions (localized rapid mutation acceptance) altering the biological properties of both insulin and glucagon have been revealed, but this does not appear to be the case with either pancreatic polypeptide or those regions of guinea pig insulin receptor cDNAs that have been examined thus far. These findings suggest that novel selective pressures operative in the New World environment, in which these animals evolved in isolation from Old World mammalian species, have led to altered solutions to problems related to the regulation of growth and carbohydrate metabolism.

T7 phage displaying latent membrane protein 1 of Epstein-Barr virus elicits humoral and cellular immune responses in rats.

PubMed

Gao, J; Liu, Z; Huang, M; Li, X; Wang, Z

2011-01-01

The latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus (EBV) has become a potential target in EBV-associated tumor prevention and treatment due to its multiple biological effects. In this study, the recombinant T7 phage displaying full-length LMP1 protein was cloned and used as an immunogen to immunize rats. Results of flow cytometry, Western blot analysis, and ELISA confirmed that both humoral and cellular immune responses were elicited in the immunized rats. Our data suggested that T7 phage was an efficient antigen carrier. The recombinant T7-LMP1 phage reconstitutes the antigenic and immunogenic properties of LMP1 and can serve as a vaccine against EBV.

Chemical biology 2012: from drug targets to biological systems and back.

PubMed

Socher, Elke; Grossmann, Tom N

2013-01-02

Multiple sites sharing a common target: This year's EMBO conference on chemical biology encouraged over 340 researchers to come to Heidelberg, Germany, and discuss the use of diverse chemical strategies and tools to investigate biological questions and better understand cellular processes. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mechanical Fluidity of Fully Suspended Biological Cells

PubMed Central

Maloney, John M.; Lehnhardt, Eric; Long, Alexandra F.; Van Vliet, Krystyn J.

2013-01-01

Mechanical characteristics of single biological cells are used to identify and possibly leverage interesting differences among cells or cell populations. Fluidity—hysteresivity normalized to the extremes of an elastic solid or a viscous liquid—can be extracted from, and compared among, multiple rheological measurements of cells: creep compliance versus time, complex modulus versus frequency, and phase lag versus frequency. With multiple strategies available for acquisition of this nondimensional property, fluidity may serve as a useful and robust parameter for distinguishing cell populations, and for understanding the physical origins of deformability in soft matter. Here, for three disparate eukaryotic cell types deformed in the suspended state via optical stretching, we examine the dependence of fluidity on chemical and environmental influences at a timescale of ∼1 s. We find that fluidity estimates are consistent in the time and frequency domains under a structural damping (power-law or fractional-derivative) model, but not under an equivalent-complexity, lumped-component (spring-dashpot) model; the latter predicts spurious time constants. Although fluidity is suppressed by chemical cross-linking, we find that ATP depletion in the cell does not measurably alter the parameter, and we thus conclude that active ATP-driven events are not a crucial enabler of fluidity during linear viscoelastic deformation of a suspended cell. Finally, by using the capacity of optical stretching to produce near-instantaneous increases in cell temperature, we establish that fluidity increases with temperature—now measured in a fully suspended, sortable cell without the complicating factor of cell-substratum adhesion. PMID:24138852

Biogeochemical and hydrological constraints on concentration-discharge curves

NASA Astrophysics Data System (ADS)

Moatar, Florentina; Abbott, Ben; Minaudo, Camille; Curie, Florence; Pinay, Gilles

2017-04-01

The relationship between concentration and discharge (C-Q) can give insight into the location, abundance, rate of production or consumption, and transport dynamics of elements in coupled terrestrial-aquatic ecosystems. Consequently, the investigation of C-Q relationships for multiple elements at multiple spatial and temporal scales can be a powerful tool to address three of ecohydrology's fundamental questions: where does water comes from, how long does it stay, and what happens to the solutes and particulates it carries along the way. We analyzed long-term water quality data from 300 monitoring stations covering nearly half of France to investigate how elemental properties, catchment characteristics, and hydrological parameters influence C-Q. Based on previous work, we segmented the hydrograph, calculating independent C-Q slopes for flows above and below the median discharge. We found that most elements only expressed two of the nine possible C-Q modalities, indicating strong elemental control of C-Q shape. Catchment characteristics including land use and human population had a strong impact on concentration but typically did not influence the C-Q slopes, also suggesting inherent constraints on elemental production and transport. Biological processes appeared to regulate C-Q slope at low flows for biologically-reactive elements, but at high flows, these processes became unimportant, and most parameters expressed chemostatic behavior. This study provides a robust description of possible C-Q shapes for a wide variety of catchments and elements and demonstrates the value of low-frequency, long-term data collected by water quality agencies.

Minocycline: far beyond an antibiotic

PubMed Central

Garrido-Mesa, N; Zarzuelo, A; Gálvez, J

2013-01-01

Minocycline is a second-generation, semi-synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram-positive and gram-negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti-microbial activity, including anti-inflammatory and anti-apoptotic activities, and inhibition of proteolysis, angiogenesis and tumour metastasis. These findings specifically concern to minocycline as it has recently been found to have multiple non-antibiotic biological effects that are beneficial in experimental models of various diseases with an inflammatory basis, including dermatitis, periodontitis, atherosclerosis and autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury. Moreover, other pre-clinical studies have shown its ability to inhibit malignant cell growth and activation and replication of human immunodeficiency virus, and to prevent bone resorption. Considering the above-mentioned findings, this review will cover the most important topics in the pharmacology of minocycline to date, supporting its evaluation as a new therapeutic approach for many of the diseases described herein. PMID:23441623

Immobilization and long-term recovery results in large changes in bone structure and strength but no corresponding alterations of osteocyte lacunar properties.

PubMed

Bach-Gansmo, Fiona Linnea; Wittig, Nina Kølln; Brüel, Annemarie; Thomsen, Jesper Skovhus; Birkedal, Henrik

2016-10-01

The ability of osteocytes to demineralize the perilacunar matrix, osteocytic osteolysis, and thereby participate directly in bone metabolism, is an aspect of osteocyte biology that has received increasing attention during the last couple of years. The aim of the present work was to investigate whether osteocyte lacunar properties change during immobilization and subsequent recovery. A rat cortical bone model with negligible Haversian remodeling effects was used, with temporary immobilization of one hindlimb induced by botulinum toxin. Several complementary techniques covering multiple length scales enabled correlation of osteocyte lacunar properties to changes observed on the organ and tissue level of femoral bone. Bone structural parameters measured by μCT and mechanical properties were compared to sub-micrometer resolution SR μCT data mapping an unprecedented number (1.85 million) of osteocyte lacunae. Immobilization induced a significant reduction in aBMD, bone volume, tissue volume, and load to fracture, as well as the muscle mass of rectus femoris. During the subsequent recovery period, the bone structural and mechanical properties were only partly regained in spite of a long-term (28weeks) study period. No significant changes in osteocyte lacunar volume, density, oblateness, stretch, or orientation were detected upon immobilization or subsequent recovery. In conclusion, the bone architecture and not osteocyte lacunar properties or bone material characteristics dominate the immobilization response as well as the subsequent recovery. Copyright © 2016 Elsevier Inc. All rights reserved.

[Intellectual property rights in Costa Rica in the light of the Biodiversity Convention].

PubMed

Salazar, R; Cabrera, J A

1996-04-01

This report analyzes intellectual property rights and acquisition of biological samples in light of the Biological Diversity Convention, with emphasis on Costa Rica. It examines the legal framework which exists for the protection of biological resources in this country, especially evaluating the law regarding protection of biota, which was approved in 1992. This includes information regarding access to genetic resources, and regulation for the aforementioned law. It examines the Biological Diversity Convention which was signed at the Rio Summit in 1992, whose objectives and goals, above all, emphasize the subject of distribution of benefits to be derived from the utilization of biological resources.

PROMISE: a tool to identify genomic features with a specific biologically interesting pattern of associations with multiple endpoint variables

PubMed Central

Pounds, Stan; Cheng, Cheng; Cao, Xueyuan; Crews, Kristine R.; Plunkett, William; Gandhi, Varsha; Rubnitz, Jeffrey; Ribeiro, Raul C.; Downing, James R.; Lamba, Jatinder

2009-01-01

Motivation: In some applications, prior biological knowledge can be used to define a specific pattern of association of multiple endpoint variables with a genomic variable that is biologically most interesting. However, to our knowledge, there is no statistical procedure designed to detect specific patterns of association with multiple endpoint variables. Results: Projection onto the most interesting statistical evidence (PROMISE) is proposed as a general procedure to identify genomic variables that exhibit a specific biologically interesting pattern of association with multiple endpoint variables. Biological knowledge of the endpoint variables is used to define a vector that represents the biologically most interesting values for statistics that characterize the associations of the endpoint variables with a genomic variable. A test statistic is defined as the dot-product of the vector of the observed association statistics and the vector of the most interesting values of the association statistics. By definition, this test statistic is proportional to the length of the projection of the observed vector of correlations onto the vector of most interesting associations. Statistical significance is determined via permutation. In simulation studies and an example application, PROMISE shows greater statistical power to identify genes with the interesting pattern of associations than classical multivariate procedures, individual endpoint analyses or listing genes that have the pattern of interest and are significant in more than one individual endpoint analysis. Availability: Documented R routines are freely available from www.stjuderesearch.org/depts/biostats and will soon be available as a Bioconductor package from www.bioconductor.org. Contact: stanley.pounds@stjude.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19528086

The diverse biological properties of the chemically inert noble gases.

PubMed

Winkler, David A; Thornton, Aaron; Farjot, Géraldine; Katz, Ira

2016-04-01

The noble gases represent an intriguing scientific paradox. They are extremely inert chemically but display a remarkable spectrum of clinically useful biological properties. Despite a relative paucity of knowledge of their mechanisms of action, some of the noble gases have been used successfully in the clinic. Studies with xenon have suggested that the noble gases as a class may exhibit valuable biological properties such as anaesthesia; amelioration of ischemic damage; tissue protection prior to transplantation; analgesic properties; and a potentially wide range of other clinically useful effects. Xenon has been shown to be safe in humans, and has useful pharmacokinetic properties such as rapid onset, fast wash out etc. The main limitations in wider use are that: many of the fundamental biochemical studies are still lacking; the lighter noble gases are likely to manifest their properties only under hyperbaric conditions, impractical in surgery; and administration of xenon using convectional gaseous anaesthesia equipment is inefficient, making its use very expensive. There is nonetheless a significant body of published literature on the biochemical, pharmacological, and clinical properties of noble gases but no comprehensive reviews exist that summarize their properties and the existing knowledge of their models of action at the molecular (atomic) level. This review provides such an up-to-date summary of the extensive, useful biological properties of noble gases as drugs and prospects for wider application of these atoms. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

The wettability and swelling of selected mucoadhesive polymers in simulated saliva and vaginal fluids.

PubMed

Rojewska, M; Olejniczak-Rabinek, M; Bartkowiak, A; Snela, A; Prochaska, K; Lulek, J

2017-08-01

The surface properties play a particularly important role in the mucoadhesive drug delivery systems. In these formulations, the adsorption of polymer matrix to mucous membrane is limited by the wetting and swelling process of the polymer structure. Hence, the performance of mucoadhesive drug delivery systems made of polymeric materials depends on multiple factors, such as contact angle, surface free energy and water absorption rate. The aim of our study was to analyze the effect of model saliva and vaginal fluids on the wetting properties of selected mucoadhesive (Carbopol 974P NF, Noveon AA-1, HEC) and film-forming (Kollidon VA 64) polymers as well as their blends at the weight ratio 1:1 and 1:1:1, prepared in the form of discs. Surface properties of the discs were determined by measurements of advancing contact angle on the surface of polymers and their blends using the sessile drop method. The surface energy was determined by the OWRK method. Additionally, the mass swelling factor and hydration percentage of examined polymers and their blends in simulated biological fluids were evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

Advances in vascular tissue engineering.

PubMed

Thomas, Anita C; Campbell, Gordon R; Campbell, Julie H

2003-01-01

Coronary and peripheral artery bypass grafting is commonly used to relieve the symptoms of vascular deficiencies, but the supply of autologous artery or vein may not be sufficient or suitable for multiple bypass or repeat procedures, necessitating the use of other materials. Synthetic materials are suitable for large bore arteries but often thrombose when used in smaller arteries. Suitable replacement grafts must have appropriate characteristics, including resistance to infection, low immunogenicity and good biocompatability and thromboresistance, with appropriate mechanical and physiological properties and cheap and fast manufacture. Current avenues of graft development include coating synthetic grafts with either biological chemicals or cells with anticoagulatory properties. Matrix templates or acellular tubes of extracellular matrix (such as collagen) may be coated or infiltrated with cultured cells. Once placed into the artery, these grafts may become colonised by host cells and gain many of the properties of normal artery. "Tissue-engineered blood vessels" may also be formed from layers of human vascular cells grown in culture. These engineered vessels have many of the characteristics of arteries formed in vivo. "Artificial arteries" may be also be derived from peritoneal granulation tissue in body "bioreactors" by adapting the body's natural wound healing response to produce a hollow tube.

Biological functions of iduronic acid in chondroitin/dermatan sulfate.

PubMed

Thelin, Martin A; Bartolini, Barbara; Axelsson, Jakob; Gustafsson, Renata; Tykesson, Emil; Pera, Edgar; Oldberg, Åke; Maccarana, Marco; Malmstrom, Anders

2013-05-01

The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides because it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties, such as migration, proliferation, differentiation, angiogenesis and the regulation of cytokine/growth factor activities. Under pathological conditions such as wound healing, inflammation and cancer, iduronic acid has diverse regulatory functions. Iduronic acid is formed by two epimerases (i.e. dermatan sulfate epimerase 1 and 2) that have different tissue distribution and properties. The role of iduronic acid in chondroitin/dermatan sulfate is highlighted by the vast changes in connective tissue features in patients with a new type of Ehler-Danlos syndrome: adducted thumb-clubfoot syndrome. Future research aims to understand the roles of the two epimerases and their interplay with the sulfotransferases involved in chondroitin sulfate/dermatan sulfate biosynthesis. Furthermore, a better definition of chondroitin/dermatan sulfate functions using different knockout models is needed. In this review, we focus on the two enzymes responsible for iduronic acid formation, as well as the role of iduronic acid in health and disease. © 2013 The Authors Journal compilation © 2013 FEBS.

Detecting Biological Warfare Agents

PubMed Central

Song, Linan; Ahn, Soohyoun

2005-01-01

We developed a fiber-optic, microsphere-based, high-density array composed of 18 species-specific probe microsensors to identify biological warfare agents. We simultaneously identified multiple biological warfare agents in environmental samples by looking at specific probe responses after hybridization and response patterns of the multiplexed array. PMID:16318712

Chitooligosaccharide: An evaluation of physicochemical and biological properties with the proposition for determination of thermal degradation products.

PubMed

Phil, Lucas; Naveed, Muhammad; Mohammad, Imran Shair; Bo, Li; Bin, Di

2018-06-01

Being the most versatile biopolymer, chitooligosaccharide/chitosan oligosaccharide (COS) has been extensively studied for a range of exceptional biological activities and potential developments of novel medical devices and systems in biomedical and pharmaceutical fields. While possessing intrinsic biocompatibility, mucoadhesiveness, and non-toxicity it gained more interests in the biomedical development of novel systems, devices, and pharmaceutical formulations. The bioactive relativity of chitosan and COS are of highly significant and thus explored in this paper while highlighting its multiple biological activities and promising biomedical applications. More emphasis is on the molecular weight, degree of acetylation/deacetylation, degree of polymerization and reactive groups in relation to chitin and chitosan. Despite COS wide acceptance and utilization, the associated viscosity and instability are crucial factors that posed a great challenge to researchers. The apparent reason attributed to instability and viscosity could be the presence intrinsic variable oligomers within COS. Due to lack of data on safety and impurity analysis of thermal exposure of COS, we hypothesized that different molecules could be generated with thermal treatment of COS, thus finally suggested a prospective determination of thermal degradation product(s)in COS. Hence the aim of this paper is to highlight COS physicochemical and biological significance with reference to its recent developments and propose a further chemical analysis thermal treated COS. This could trigger future researchers for possible isolation and characterization of distinct biomolecules from COS. Copyright © 2018. Published by Elsevier Masson SAS.

Why Nature Chose Selenium.

PubMed

Reich, Hans J; Hondal, Robert J

2016-04-15

The authors were asked by the Editors of ACS Chemical Biology to write an article titled "Why Nature Chose Selenium" for the occasion of the upcoming bicentennial of the discovery of selenium by the Swedish chemist Jöns Jacob Berzelius in 1817 and styled after the famous work of Frank Westheimer on the biological chemistry of phosphate [Westheimer, F. H. (1987) Why Nature Chose Phosphates, Science 235, 1173-1178]. This work gives a history of the important discoveries of the biological processes that selenium participates in, and a point-by-point comparison of the chemistry of selenium with the atom it replaces in biology, sulfur. This analysis shows that redox chemistry is the largest chemical difference between the two chalcogens. This difference is very large for both one-electron and two-electron redox reactions. Much of this difference is due to the inability of selenium to form π bonds of all types. The outer valence electrons of selenium are also more loosely held than those of sulfur. As a result, selenium is a better nucleophile and will react with reactive oxygen species faster than sulfur, but the resulting lack of π-bond character in the Se-O bond means that the Se-oxide can be much more readily reduced in comparison to S-oxides. The combination of these properties means that replacement of sulfur with selenium in nature results in a selenium-containing biomolecule that resists permanent oxidation. Multiple examples of this gain of function behavior from the literature are discussed.

Multi-tissue DNA methylation age predictor in mouse.

PubMed

Stubbs, Thomas M; Bonder, Marc Jan; Stark, Anne-Katrien; Krueger, Felix; von Meyenn, Ferdinand; Stegle, Oliver; Reik, Wolf

2017-04-11

DNA methylation changes at a discrete set of sites in the human genome are predictive of chronological and biological age. However, it is not known whether these changes are causative or a consequence of an underlying ageing process. It has also not been shown whether this epigenetic clock is unique to humans or conserved in the more experimentally tractable mouse. We have generated a comprehensive set of genome-scale base-resolution methylation maps from multiple mouse tissues spanning a wide range of ages. Many CpG sites show significant tissue-independent correlations with age which allowed us to develop a multi-tissue predictor of age in the mouse. Our model, which estimates age based on DNA methylation at 329 unique CpG sites, has a median absolute error of 3.33 weeks and has similar properties to the recently described human epigenetic clock. Using publicly available datasets, we find that the mouse clock is accurate enough to measure effects on biological age, including in the context of interventions. While females and males show no significant differences in predicted DNA methylation age, ovariectomy results in significant age acceleration in females. Furthermore, we identify significant differences in age-acceleration dependent on the lipid content of the diet. Here we identify and characterise an epigenetic predictor of age in mice, the mouse epigenetic clock. This clock will be instrumental for understanding the biology of ageing and will allow modulation of its ticking rate and resetting the clock in vivo to study the impact on biological age.

Differentiating low-molecular-weight heparins based on chemical, biological, and pharmacologic properties: implications for the development of generic versions of low-molecular-weight heparins.

PubMed

Jeske, Walter P; Walenga, Jeanine M; Hoppensteadt, Debra A; Vandenberg, Curtis; Brubaker, Aleah; Adiguzel, Cafer; Bakhos, Mamdouh; Fareed, Jawed

2008-02-01

Low-molecular-weight heparins (LMWHs) are polypharmacologic drugs used to treat thrombotic and cardiovascular disorders. These drugs are manufactured using different chemical and enzymatic methods, resulting in products with distinct chemical and pharmacologic profiles. Generic LMWHs have been introduced in Asia and South America, and several generic suppliers are seeking regulatory approval in the United States and the European Union. For simple small-molecule drugs, generic drugs have the same chemical structure, potency, and bioavailability as the innovator drug. Applying this definition to complex biological products such as the LMWHs has proved difficult. One major issue is defining appropriate criteria to demonstrate bioequivalence; pharmacopoeial specifications alone appear to be inadequate. Whereas available generic versions of LMWHs exhibit similar molecular and pharmacopoeial profiles, marked differences in their biological and pharmacologic behavior have been noted. Preliminary studies have demonstrated differences in terms of anti-Xa activity and tissue factor pathway inhibitor release after subcutaneous administration, as well as antiplatelet and profibrinolytic effects. The current data emphasize the need to consider multiple functional parameters when defining bioequivalence of biologic drugs with complex structures and activities and also underscore the importance of further pharmacologic studies involving animal models and human clinical trials. The U.S. Food and Drug Administration and the European Medicine Evaluation Agency are currently developing guidelines for the acceptance of biosimilar agents including LMWHs. Until such guidelines are complete, generic interchange may not be feasible.

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.

Family structure, victimization, and child mental health in a nationally representative sample.

PubMed

Turner, Heather A; Finkelhor, David; Hamby, Sherry L; Shattuck, Anne

2013-06-01

Utilizing the 2008 National Survey of Children's Exposure to Violence (NatSCEV), the current study compares past year rates of 7 forms of child victimization (maltreatment, assault, peer victimization, property crime, witnessing family violence and exposure to community violence) across 3 different family structure types (two biological/adoptive parents, single parent, step/cohabiting family) among a representative sample of 4046 U.S. children ages 2-17. The study also considers whether certain social-contextual risk factors help to explain family structure variations in victimization, and the extent to which victimization exposure accounts for family structure differences in distress symptom levels. Findings showed significantly elevated rates of almost all types of victimization among children in both nontraditional family types, relative to those living with two biological/adoptive parents. Factors associated with increased victimization risk in these families include high parental conflict, drug or alcohol problems, family adversity, and community disorder. A summary measure of children's exposure to multiple forms of victimization was the strongest predictor of distress symptoms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reliability Methods for Shield Design Process

NASA Technical Reports Server (NTRS)

Tripathi, R. K.; Wilson, J. W.

2002-01-01

Providing protection against the hazards of space radiation is a major challenge to the exploration and development of space. The great cost of added radiation shielding is a potential limiting factor in deep space operations. In this enabling technology, we have developed methods for optimized shield design over multi-segmented missions involving multiple work and living areas in the transport and duty phase of space missions. The total shield mass over all pieces of equipment and habitats is optimized subject to career dose and dose rate constraints. An important component of this technology is the estimation of two most commonly identified uncertainties in radiation shield design, the shielding properties of materials used and the understanding of the biological response of the astronaut to the radiation leaking through the materials into the living space. The largest uncertainty, of course, is in the biological response to especially high charge and energy (HZE) ions of the galactic cosmic rays. These uncertainties are blended with the optimization design procedure to formulate reliability-based methods for shield design processes. The details of the methods will be discussed.

Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols.

PubMed

Shi, Shi-Liang; Wong, Zackary L; Buchwald, Stephen L

2016-04-21

The chirality, or 'handedness', of a biologically active molecule can alter its physiological properties. Thus it is routine procedure in the drug discovery and development process to prepare and fully characterize all possible stereoisomers of a drug candidate for biological evaluation. Despite many advances in asymmetric synthesis, developing general and practical strategies for obtaining all possible stereoisomers of an organic compound that has multiple contiguous stereocentres remains a challenge. Here, we report a stereodivergent copper-based approach for the expeditious construction of amino alcohols with high levels of chemo-, regio-, diastereo- and enantioselectivity. Specifically, we synthesized these amino-alcohol products using sequential, copper-hydride-catalysed hydrosilylation and hydroamination of readily available enals and enones. This strategy provides a route to all possible stereoisomers of the amino-alcohol products, which contain up to three contiguous stereocentres. We leveraged catalyst control and stereospecificity simultaneously to attain exceptional control of the product stereochemistry. Beyond the immediate utility of this protocol, our strategy could inspire the development of methods that provide complete sets of stereoisomers for other valuable synthetic targets.

Enzymatic modification of phospholipids for functional applications and human nutrition.

PubMed

Guo, Zheng; Vikbjerg, Anders F; Xu, Xuebing

2005-05-01

Rapid progress in biochemistry of phospholipids and evolution of modern bioengineering has brought forth a number of novel concepts and technical advancements in the modification of phospholipids for industrial applications and human nutrition. Highlights cover preparation of novel phospholipid analogs based on the latest understanding of pivotal role of phospholipids in manifold biological processes, exploration of remarkable application potentials of phospholipids in meliorating human health, as well as development of new chemical and biotechnological approaches applied to the modification of phospholipids. This work reviews the natural occurrence and structural characteristics of phospholipids, their updated knowledge on manifold biological and nutritional functions, traditional and novel physical and chemical approaches to modify phospholipids as well as their applications to obtain novel phospholipids, and brief introduction of the efforts focusing on de novo syntheses of phospholipids. Special attention is given to the summary of molecular structural characteristics and catalytic properties of multiple phospholipases, which helps to interpret experimental phenomena and to improve reaction design. This will of course provide fundamental bases also for the development of enzymatic technology to produce structured or modified phospholipids.

Structures and physical properties of gaseous metal cationized biological ions.

PubMed

Burt, Michael B; Fridgen, Travis D

2012-01-01

Metal chelation can alter the activity of free biomolecules by modifying their structures or stabilizing higher energy tautomers. In recent years, mass spectrometric techniques have been used to investigate the effects of metal complexation with proteins, nucleobases and nucleotides, where small conformational changes can have significant physiological consequences. In particular, infrared multiple photon dissociation spectroscopy has emerged as an important tool for determining the structure and reactivity of gas-phase ions. Unlike other mass spectrometric approaches, this method is able to directly resolve structural isomers using characteristic vibrational signatures. Other activation and dissociation methods, such as blackbody infrared radiative dissociation or collision-induced dissociation can also reveal information about the thermochemistry and dissociative pathways of these biological ions. This information can then be used to provide information about the structures of the ionic complexes under study. In this article, we review the use of gas-phase techniques in characterizing metal-bound biomolecules. Particular attention will be given to our own contributions, which detail the ability of metal cations to disrupt nucleobase pairs, direct the self-assembly of nucleobase clusters and stabilize non-canonical isomers of amino acids.

Carbon Nanotropes: A Contemporary Paradigm in Drug Delivery

PubMed Central

Tripathi, Avinash C.; Saraf, Shubhini A.; Saraf, Shailendra K.

2015-01-01

Discovery of fullerenes and other nanosized carbon allotropes has opened a vast new field of possibilities in nanotechnology and has become one of the most promising research areas. Carbon nanomaterials have drawn interest as carriers of biologically pertinent molecules due to their distinctive physical, chemical and physiological properties. We have assigned the nomenclature “Carbon Nanotropes” to the nanosized carbon allotropes. Carbon nanotropes such as fullerenes, carbon nanotubes (CNTs) and graphenes, have exhibited wide applicability in drug delivery, owing to their small size and biological activity. The nanotherapeutics/diagnostics will allow a deeper understanding of human ills including cancer, neurodegenerative diseases, genetic disorders and various other complications. Recently, nanomaterials with multiple functions, such as drug carrier, MRI, optical imaging, photothermal therapy, etc., have become more and more popular in the domain of cancer and other areas of research. This review is an endeavor to bring together the usefulness of the carbon nanomaterials in the field of drug delivery. The last section of the review encompasses the recent patents granted on carbon nanotropes at United State Patent Trademark Office (USPTO) in the related field.

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.

BIOPEP database and other programs for processing bioactive peptide sequences.

PubMed

Minkiewicz, Piotr; Dziuba, Jerzy; Iwaniak, Anna; Dziuba, Marta; Darewicz, Małgorzata

2008-01-01

This review presents the potential for application of computational tools in peptide science based on a sample BIOPEP database and program as well as other programs and databases available via the World Wide Web. The BIOPEP application contains a database of biologically active peptide sequences and a program enabling construction of profiles of the potential biological activity of protein fragments, calculation of quantitative descriptors as measures of the value of proteins as potential precursors of bioactive peptides, and prediction of bonds susceptible to hydrolysis by endopeptidases in a protein chain. Other bioactive and allergenic peptide sequence databases are also presented. Programs enabling the construction of binary and multiple alignments between peptide sequences, the construction of sequence motifs attributed to a given type of bioactivity, searching for potential precursors of bioactive peptides, and the prediction of sites susceptible to proteolytic cleavage in protein chains are available via the Internet as are other approaches concerning secondary structure prediction and calculation of physicochemical features based on amino acid sequence. Programs for prediction of allergenic and toxic properties have also been developed. This review explores the possibilities of cooperation between various programs.

Design and Control of Compliant Tensegrity Robots Through Simulation and Hardware Validation

NASA Technical Reports Server (NTRS)

Caluwaerts, Ken; Despraz, Jeremie; Iscen, Atil; Sabelhaus, Andrew P.; Bruce, Jonathan; Schrauwen, Benjamin; Sunspiral, Vytas

2014-01-01

To better understand the role of tensegrity structures in biological systems and their application to robotics, the Dynamic Tensegrity Robotics Lab at NASA Ames Research Center has developed and validated two different software environments for the analysis, simulation, and design of tensegrity robots. These tools, along with new control methodologies and the modular hardware components developed to validate them, are presented as a system for the design of actuated tensegrity structures. As evidenced from their appearance in many biological systems, tensegrity ("tensile-integrity") structures have unique physical properties which make them ideal for interaction with uncertain environments. Yet these characteristics, such as variable structural compliance, and global multi-path load distribution through the tension network, make design and control of bio-inspired tensegrity robots extremely challenging. This work presents the progress in using these two tools in tackling the design and control challenges. The results of this analysis includes multiple novel control approaches for mobility and terrain interaction of spherical tensegrity structures. The current hardware prototype of a six-bar tensegrity, code-named ReCTeR, is presented in the context of this validation.

Herbal Remedies for Coccidiosis Control: A Review of Plants, Compounds, and Anticoccidial Actions

PubMed Central

Muthamilselvan, Thangarasu; Wu, Yueh-Chen

2016-01-01

Coccidiosis is the bane of the poultry industry causing considerable economic loss. Eimeria species are known as protozoan parasites to cause morbidity and death in poultry. In addition to anticoccidial chemicals and vaccines, natural products are emerging as an alternative and complementary way to control avian coccidiosis. In this review, we update recent advances in the use of anticoccidial phytoextracts and phytocompounds, which cover 32 plants and 40 phytocompounds, following a database search in PubMed, Web of Science, and Google Scholar. Four plant products commercially available for coccidiosis are included and discussed. We also highlight the chemical and biological properties of the plants and compounds as related to coccidiosis control. Emphasis is placed on the modes of action of the anticoccidial plants and compounds such as interference with the life cycle of Eimeria, regulation of host immunity to Eimeria, growth regulation of gut bacteria, and/or multiple mechanisms. Biological actions, mechanisms, and prophylactic/therapeutic potential of the compounds and extracts of plant origin in coccidiosis are summarized and discussed. PMID:27429634

Evidence Combination From an Evolutionary Game Theory Perspective.

PubMed

Deng, Xinyang; Han, Deqiang; Dezert, Jean; Deng, Yong; Shyr, Yu

2016-09-01

Dempster-Shafer evidence theory is a primary methodology for multisource information fusion because it is good at dealing with uncertain information. This theory provides a Dempster's rule of combination to synthesize multiple evidences from various information sources. However, in some cases, counter-intuitive results may be obtained based on that combination rule. Numerous new or improved methods have been proposed to suppress these counter-intuitive results based on perspectives, such as minimizing the information loss or deviation. Inspired by evolutionary game theory, this paper considers a biological and evolutionary perspective to study the combination of evidences. An evolutionary combination rule (ECR) is proposed to help find the most biologically supported proposition in a multievidence system. Within the proposed ECR, we develop a Jaccard matrix game to formalize the interaction between propositions in evidences, and utilize the replicator dynamics to mimick the evolution of propositions. Experimental results show that the proposed ECR can effectively suppress the counter-intuitive behaviors appeared in typical paradoxes of evidence theory, compared with many existing methods. Properties of the ECR, such as solution's stability and convergence, have been mathematically proved as well.

Euclea undulata Thunb.: Review of its botany, ethnomedicinal uses, phytochemistry and biological activities.

PubMed

Maroyi, Alfred

2017-11-01

Euclea undulata (E. undulata) is traditionally used for the treatment of body pains, chest complaints, cough, diabetes, diarrhoea, headaches, heart diseases and toothaches in southern Africa. This study was aimed at reviewing the botany, ethnopharmacology and biological activities of E. undulata in southern Africa. Results presented in this study are based on review of literature using search engines such as Science Direct, Springerlink, Scopus, PubMed, Web of Science, BioMed Central and Google Scholar. Herbal medicine is prepared from the decoctions of the roots, bark and leaves, and extracts of these plant parts have demonstrated anticholinesterase, anti-inflammatory, antimicrobial, antimycobacterial, antiplasmodial, antioxidant and hypoglycaemic activities. Multiple classes of phytochemical compounds such alkaloids, diterpenes, fatty acids, flavonoids, glycosides, naphthoquinones, phenolics, phytosterols, reducing sugars, saponins and tannins have been isolated from the species. E. undulata has a lot of potential as herbal medicine in tropical Africa, and advanced research is required aimed at correlating its medicinal uses with the phytochemistry and pharmacological properties. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Antagonistic autoregulation speeds up a homogeneous response in Escherichia coli.

PubMed

Rodrigo, Guillermo; Bajic, Djordje; Elola, Ignacio; Poyatos, Juan F

2016-10-31

By integrating positive and negative feedback loops, biological systems establish intricate gene expression patterns linked to multistability, pulsing, and oscillations. This depends on the specific characteristics of each interlinked feedback, and thus one would expect additional expression programs to be found. Here, we investigate one such program associated with an antagonistic positive and negative transcriptional autoregulatory motif derived from the multiple antibiotic resistance (mar) system of Escherichia coli. We studied the dynamics of the system by combining a predictive mathematical model with high-resolution experimental measures of the response both at the population and single-cell level. We show that in this motif the weak positive autoregulation does not slow down but rather enhances response speedup in combination with a strong negative feedback loop. This balance of feedback strengths anticipates a homogeneous population phenotype, which we corroborate experimentally. Theoretical analysis also emphasized the specific molecular properties that determine the dynamics of the mar phenotype. More broadly, response acceleration could provide a rationale for the presence of weak positive feedbacks in other biological scenarios exhibiting these interlinked regulatory architectures.

Systems pharmacology - Towards the modeling of network interactions.

PubMed

Danhof, Meindert

2016-10-30

Mechanism-based pharmacokinetic and pharmacodynamics (PKPD) and disease system (DS) models have been introduced in drug discovery and development research, to predict in a quantitative manner the effect of drug treatment in vivo in health and disease. This requires consideration of several fundamental properties of biological systems behavior including: hysteresis, non-linearity, variability, interdependency, convergence, resilience, and multi-stationarity. Classical physiology-based PKPD models consider linear transduction pathways, connecting processes on the causal path between drug administration and effect, as the basis of drug action. Depending on the drug and its biological target, such models may contain expressions to characterize i) the disposition and the target site distribution kinetics of the drug under investigation, ii) the kinetics of target binding and activation and iii) the kinetics of transduction. When connected to physiology-based DS models, PKPD models can characterize the effect on disease progression in a mechanistic manner. These models have been found useful to characterize hysteresis and non-linearity, yet they fail to explain the effects of the other fundamental properties of biological systems behavior. Recently systems pharmacology has been introduced as novel approach to predict in vivo drug effects, in which biological networks rather than single transduction pathways are considered as the basis of drug action and disease progression. These models contain expressions to characterize the functional interactions within a biological network. Such interactions are relevant when drugs act at multiple targets in the network or when homeostatic feedback mechanisms are operative. As a result systems pharmacology models are particularly useful to describe complex patterns of drug action (i.e. synergy, oscillatory behavior) and disease progression (i.e. episodic disorders). In this contribution it is shown how physiology-based PKPD and disease models can be extended to account for internal systems interactions. It is demonstrated how SP models can be used to predict the effects of multi-target interactions and of homeostatic feedback on the pharmacological response. In addition it is shown how DS models may be used to distinguish symptomatic from disease modifying effects and to predict the long term effects on disease progression, from short term biomarker responses. It is concluded that incorporation of expressions to describe the interactions in biological network analysis opens new avenues to the understanding of the effects of drug treatment on the fundamental aspects of biological systems behavior. Copyright © 2016 The Author. Published by Elsevier B.V. All rights reserved.

Integrative Exploratory Analysis of Two or More Genomic Datasets.

PubMed

Meng, Chen; Culhane, Aedin

2016-01-01

Exploratory analysis is an essential step in the analysis of high throughput data. Multivariate approaches such as correspondence analysis (CA), principal component analysis, and multidimensional scaling are widely used in the exploratory analysis of single dataset. Modern biological studies often assay multiple types of biological molecules (e.g., mRNA, protein, phosphoproteins) on a same set of biological samples, thereby creating multiple different types of omics data or multiassay data. Integrative exploratory analysis of these multiple omics data is required to leverage the potential of multiple omics studies. In this chapter, we describe the application of co-inertia analysis (CIA; for analyzing two datasets) and multiple co-inertia analysis (MCIA; for three or more datasets) to address this problem. These methods are powerful yet simple multivariate approaches that represent samples using a lower number of variables, allowing a more easily identification of the correlated structure in and between multiple high dimensional datasets. Graphical representations can be employed to this purpose. In addition, the methods simultaneously project samples and variables (genes, proteins) onto the same lower dimensional space, so the most variant variables from each dataset can be selected and associated with samples, which can be further used to facilitate biological interpretation and pathway analysis. We applied CIA to explore the concordance between mRNA and protein expression in a panel of 60 tumor cell lines from the National Cancer Institute. In the same 60 cell lines, we used MCIA to perform a cross-platform comparison of mRNA gene expression profiles obtained on four different microarray platforms. Last, as an example of integrative analysis of multiassay or multi-omics data we analyzed transcriptomic, proteomic, and phosphoproteomic data from pluripotent (iPS) and embryonic stem (ES) cell lines.

Microbiome studies in the biological control of plant pathogens

USDA-ARS?s Scientific Manuscript database

Biological control of plant pathogens, although it has been a successful alternative that has allowed to select microorganisms for the generation of bioproducts and to understand multiple biological mechanisms, cannot be considered as a strategy defined only from the selection of a range of cultiva...

Laser biostimulation of patients suffering from multiple sclerosis in respect to the biological influence of laser light

NASA Astrophysics Data System (ADS)

Peszynski-Drews, Cezary; Klimek, Andrzej; Sopinski, Marek; Obrzejta, Dominik

2003-10-01

The authors discuss the results, obtained so far during three years' clinical examination, of laser therapy in the treatment of patients suffering from multiple sclerosis. They regard both the results of former laboratory experiments and so far discovered mechanisms of biological influence of laser light as an objective explanation of high effectiveness of laser therapy in the csae of this so far incurable disease. They discuss wide range of biological mechanisms of laser therapy, examined so far on different levels (cell, tissue, organ), allowing the explanation of beneficial influence of laser light in pathogenetically different morbidities.

Defining the "like" in "begetting the like": The development of inductive inference in the domain of biology

NASA Astrophysics Data System (ADS)

Lo, Ya-Fen

There are evidences that very young children consider linguistic labels when making similarity judgment and inductive inferences. However, it remains unclear how labels contribute to young children's similarity judgment and inductive inferences. It has been demonstrated that labels facilitate categorical memberships about objects in young children's similarity judgment and inductive inferences. It is also suggested that young children should rely on several sources of information when making similarity judgment and inductive inferences. Three experiments were conducted to examine these interpretations, in which biological information, labeling information, and perceptual similarity information were varied in a systematic manner. Three- to eleven-year-old children were asked to judge which of two Test animals a baby animals would share biological properties with. In Experiment 1, preschool children demonstrated a basic understanding of the importance of biological information for generalizing biological properties. In Experiment 2, when the labeling information became available, young children relied on linguistic labels rather than on biological information when generalizing biological properties. At the same time, 9- to 11-year-old children relied consistently on biological information. Experiment 3 supported the results of Experiment 2 and suggested that in addition to labels, perceptual similarity also contributed to children's inductive inferences.

New scaling relation for information transfer in biological networks

PubMed Central

Kim, Hyunju; Davies, Paul; Walker, Sara Imari

2015-01-01

We quantify characteristics of the informational architecture of two representative biological networks: the Boolean network model for the cell-cycle regulatory network of the fission yeast Schizosaccharomyces pombe (Davidich et al. 2008 PLoS ONE 3, e1672 (doi:10.1371/journal.pone.0001672)) and that of the budding yeast Saccharomyces cerevisiae (Li et al. 2004 Proc. Natl Acad. Sci. USA 101, 4781–4786 (doi:10.1073/pnas.0305937101)). We compare our results for these biological networks with the same analysis performed on ensembles of two different types of random networks: Erdös–Rényi and scale-free. We show that both biological networks share features in common that are not shared by either random network ensemble. In particular, the biological networks in our study process more information than the random networks on average. Both biological networks also exhibit a scaling relation in information transferred between nodes that distinguishes them from random, where the biological networks stand out as distinct even when compared with random networks that share important topological properties, such as degree distribution, with the biological network. We show that the most biologically distinct regime of this scaling relation is associated with a subset of control nodes that regulate the dynamics and function of each respective biological network. Information processing in biological networks is therefore interpreted as an emergent property of topology (causal structure) and dynamics (function). Our results demonstrate quantitatively how the informational architecture of biologically evolved networks can distinguish them from other classes of network architecture that do not share the same informational properties. PMID:26701883

Physical, chemical, and biological properties of soil under soybean cultivation and at an adjacent rainforest in Amazonia

Treesearch

T.P. Beldini; R.C. Oliveira Junior; Michael Keller; P.B. de Camargo; P.M. Crill; A. Damasceno da Silva; D. Bentes dos Santos; D. Rocha de Oliveira

2015-01-01

Land-use change in the Amazon basin has occurred at an accelerated pace during the last decade, and it is important that the effects induced by these changes on soil properties are better understood. This study investigated the chemical, physical, and biological properties of soil in a field under cultivation of soy and rice, and at an adjacent primary rain forest....

A Diagnostic Assessment for Introductory Molecular and Cell Biology

ERIC Educational Resources Information Center

Shi, Jia; Wood, William B.; Martin, Jennifer M.; Guild, Nancy A.; Vicens, Quentin; Knight, Jennifer K.

2010-01-01

We have developed and validated a tool for assessing understanding of a selection of fundamental concepts and basic knowledge in undergraduate introductory molecular and cell biology, focusing on areas in which students often have misconceptions. This multiple-choice Introductory Molecular and Cell Biology Assessment (IMCA) instrument is designed…

Biological auctions with multiple rewards

PubMed Central

Reiter, Johannes G.; Kanodia, Ayush; Gupta, Raghav; Nowak, Martin A.; Chatterjee, Krishnendu

2015-01-01

The competition for resources among cells, individuals or species is a fundamental characteristic of evolution. Biological all-pay auctions have been used to model situations where multiple individuals compete for a single resource. However, in many situations multiple resources with various values exist and single reward auctions are not applicable. We generalize the model to multiple rewards and study the evolution of strategies. In biological all-pay auctions the bid of an individual corresponds to its strategy and is equivalent to its payment in the auction. The decreasingly ordered rewards are distributed according to the decreasingly ordered bids of the participating individuals. The reproductive success of an individual is proportional to its fitness given by the sum of the rewards won minus its payments. Hence, successful bidding strategies spread in the population. We find that the results for the multiple reward case are very different from the single reward case. While the mixed strategy equilibrium in the single reward case with more than two players consists of mostly low-bidding individuals, we show that the equilibrium can convert to many high-bidding individuals and a few low-bidding individuals in the multiple reward case. Some reward values lead to a specialization among the individuals where one subpopulation competes for the rewards and the other subpopulation largely avoids costly competitions. Whether the mixed strategy equilibrium is an evolutionarily stable strategy (ESS) depends on the specific values of the rewards. PMID:26180069

Design and characterization of nanomaterial-biomolecule conjugates

NASA Astrophysics Data System (ADS)

Yim, Tae-Jin

In the field of nanobiotechnology, nanoscale dimensions result in physical properties that differ from more conventional bulk material state. The integration of nanomaterials with biomolecules has begun to be used for unique physical properties, and for biological specific recognition, thereby leading to novel nanomaterial-biomolecule conjugates. The direction of this dissertation is to develop biocatalytic nanomaterial-biomolecule conjugates and to characterize them. For this, biological catalysts are employed to combine with nanomaterials. Two large parts include functional ization of nanomaterials with biomolecules and assembly of nanomaterials using a biological catalyst. First part of this thesis work is the exploration of the biocatalytic properties of nanomaterial-biomolecule conjugates. Si nanocolumns have higher surface area which leads more amount of biocatalytis immobilization than flat Si wafer with the same projected area. The enhanced activity of soybean peroxidase (SBP) immobilized onto Si nanocolumns as novel nanostructured supports is focused. Next, the catalytic activity of immobilized DNAzyme onto multiwalled carbon nanotubes (MWNTs) is compared to that in solution phase, and multiple turnovers are examined. The relationship between hybridization efficiency and activity is investigated as a function of surface density of DNAzyme on MWNTs. Then, cellular delivery of silica nanoparticle-protein conjugates is visually confirmed and therefore the intracellular function of a protein delivered by silica nanoparticle-protein conjugates is proved. For one example of the intracellular function, stable SBP immobilized onto silica nanoparticles to activate a prodrug is demonstrated. Second part of this thesis work is the formation of nanostructured materials through the enzymatic assembly of single-walled carbon nanotubes (SWNTs). Enzymatic polymerization of a phenol compound is applied to the bridging of two or more SWNTs functionalized with phenol monomers. Next, future work based on previous works is proposed; first, the cellular delivery of DNAzyme using SWNTs is proposed to be a promising nonviral nanovehicle for gene silencing. Second, hydrophobic/hydrophilic switchable surface using DNAzyme is suggested to expand its usage to hydrophobically gradient surface. Finally, reversible assembly and disassembly of poly-L-histidine coated MWNTs can be applied to a reversible nanotube patterning on surface. And, the expansion of the works presented in this thesis to "nanomedicine" is suggested.

Quantifying bioalbedo: a new physically based model and discussion of empirical methods for characterising biological influence on ice and snow albedo

NASA Astrophysics Data System (ADS)

Cook, Joseph M.; Hodson, Andrew J.; Gardner, Alex S.; Flanner, Mark; Tedstone, Andrew J.; Williamson, Christopher; Irvine-Fynn, Tristram D. L.; Nilsson, Johan; Bryant, Robert; Tranter, Martyn

2017-11-01

The darkening effects of biological impurities on ice and snow have been recognised as a control on the surface energy balance of terrestrial snow, sea ice, glaciers and ice sheets. With a heightened interest in understanding the impacts of a changing climate on snow and ice processes, quantifying the impact of biological impurities on ice and snow albedo (bioalbedo) and its evolution through time is a rapidly growing field of research. However, rigorous quantification of bioalbedo has remained elusive because of difficulties in isolating the biological contribution to ice albedo from that of inorganic impurities and the variable optical properties of the ice itself. For this reason, isolation of the biological signature in reflectance data obtained from aerial/orbital platforms has not been achieved, even when ground-based biological measurements have been available. This paper provides the cell-specific optical properties that are required to model the spectral signatures and broadband darkening of ice. Applying radiative transfer theory, these properties provide the physical basis needed to link biological and glaciological ground measurements with remotely sensed reflectance data. Using these new capabilities we confirm that biological impurities can influence ice albedo, then we identify 10 challenges to the measurement of bioalbedo in the field with the aim of improving future experimental designs to better quantify bioalbedo feedbacks. These challenges are (1) ambiguity in terminology, (2) characterising snow or ice optical properties, (3) characterising solar irradiance, (4) determining optical properties of cells, (5) measuring biomass, (6) characterising vertical distribution of cells, (7) characterising abiotic impurities, (8) surface anisotropy, (9) measuring indirect albedo feedbacks, and (10) measurement and instrument configurations. This paper aims to provide a broad audience of glaciologists and biologists with an overview of radiative transfer and albedo that could support future experimental design.

Comparative study of classification algorithms for immunosignaturing data

PubMed Central

2012-01-01

Background High-throughput technologies such as DNA, RNA, protein, antibody and peptide microarrays are often used to examine differences across drug treatments, diseases, transgenic animals, and others. Typically one trains a classification system by gathering large amounts of probe-level data, selecting informative features, and classifies test samples using a small number of features. As new microarrays are invented, classification systems that worked well for other array types may not be ideal. Expression microarrays, arguably one of the most prevalent array types, have been used for years to help develop classification algorithms. Many biological assumptions are built into classifiers that were designed for these types of data. One of the more problematic is the assumption of independence, both at the probe level and again at the biological level. Probes for RNA transcripts are designed to bind single transcripts. At the biological level, many genes have dependencies across transcriptional pathways where co-regulation of transcriptional units may make many genes appear as being completely dependent. Thus, algorithms that perform well for gene expression data may not be suitable when other technologies with different binding characteristics exist. The immunosignaturing microarray is based on complex mixtures of antibodies binding to arrays of random sequence peptides. It relies on many-to-many binding of antibodies to the random sequence peptides. Each peptide can bind multiple antibodies and each antibody can bind multiple peptides. This technology has been shown to be highly reproducible and appears promising for diagnosing a variety of disease states. However, it is not clear what is the optimal classification algorithm for analyzing this new type of data. Results We characterized several classification algorithms to analyze immunosignaturing data. We selected several datasets that range from easy to difficult to classify, from simple monoclonal binding to complex binding patterns in asthma patients. We then classified the biological samples using 17 different classification algorithms. Using a wide variety of assessment criteria, we found ‘Naïve Bayes’ far more useful than other widely used methods due to its simplicity, robustness, speed and accuracy. Conclusions ‘Naïve Bayes’ algorithm appears to accommodate the complex patterns hidden within multilayered immunosignaturing microarray data due to its fundamental mathematical properties. PMID:22720696

Knowledge discovery and system biology in molecular medicine: an application on neurodegenerative diseases.

PubMed

Fattore, Matteo; Arrigo, Patrizio

2005-01-01

The possibility to study an organism in terms of system theory has been proposed in the past, but only the advancement of molecular biology techniques allow us to investigate the dynamical properties of a biological system in a more quantitative and rational way than before . These new techniques can gave only the basic level view of an organisms functionality. The comprehension of its dynamical behaviour depends on the possibility to perform a multiple level analysis. Functional genomics has stimulated the interest in the investigation the dynamical behaviour of an organism as a whole. These activities are commonly known as System Biology, and its interests ranges from molecules to organs. One of the more promising applications is the 'disease modeling'. The use of experimental models is a common procedure in pharmacological and clinical researches; today this approach is supported by 'in silico' predictive methods. This investigation can be improved by a combination of experimental and computational tools. The Machine Learning (ML) tools are able to process different heterogeneous data sources, taking into account this peculiarity, they could be fruitfully applied to support a multilevel data processing (molecular, cellular and morphological) that is the prerequisite for the formal model design; these techniques can allow us to extract the knowledge for mathematical model development. The aim of our work is the development and implementation of a system that combines ML and dynamical models simulations. The program is addressed to the virtual analysis of the pathways involved in neurodegenerative diseases. These pathologies are multifactorial diseases and the relevance of the different factors has not yet been well elucidated. This is a very complex task; in order to test the integrative approach our program has been limited to the analysis of the effects of a specific protein, the Cyclin dependent kinase 5 (CDK5) which relies on the induction of neuronal apoptosis. The system has a modular structure centred on a textual knowledge discovery approach. The text mining is the only way to enhance the capability to extract ,from multiple data sources, the information required for the dynamical simulator. The user may access the publically available modules through the following site: http://biocomp.ge.ismac.cnr.it.

Cryptosporidium hominis gene catalog: a resource for the selection of novel Cryptosporidium vaccine candidates

PubMed Central

Ifeonu, Olukemi O.; Simon, Raphael; Tennant, Sharon M.; Sheoran, Abhineet S.; Daly, Maria C.; Felix, Victor; Kissinger, Jessica C.; Widmer, Giovanni; Levine, Myron M.; Tzipori, Saul; Silva, Joana C.

2016-01-01

Human cryptosporidiosis, caused primarily by Cryptosporidium hominis and a subset of Cryptosporidium parvum, is a major cause of moderate-to-severe diarrhea in children under 5 years of age in developing countries and can lead to nutritional stunting and death. Cryptosporidiosis is particularly severe and potentially lethal in immunocompromised hosts. Biological and technical challenges have impeded traditional vaccinology approaches to identify novel targets for the development of vaccines against C. hominis, the predominant species associated with human disease. We deemed that the existence of genomic resources for multiple species in the genus, including a much-improved genome assembly and annotation for C. hominis, makes a reverse vaccinology approach feasible. To this end, we sought to generate a searchable online resource, termed C. hominis gene catalog, which registers all C. hominis genes and their properties relevant for the identification and prioritization of candidate vaccine antigens, including physical attributes, properties related to antigenic potential and expression data. Using bioinformatic approaches, we identified ∼400 C. hominis genes containing properties typical of surface-exposed antigens, such as predicted glycosylphosphatidylinositol (GPI)-anchor motifs, multiple transmembrane motifs and/or signal peptides targeting the encoded protein to the secretory pathway. This set can be narrowed further, e.g. by focusing on potential GPI-anchored proteins lacking homologs in the human genome, but with homologs in the other Cryptosporidium species for which genomic data are available, and with low amino acid polymorphism. Additional selection criteria related to recombinant expression and purification include minimizing predicted post-translation modifications and potential disulfide bonds. Forty proteins satisfying these criteria were selected from 3745 proteins in the updated C. hominis annotation. The immunogenic potential of a few of these is currently being tested. Database URL: http://cryptogc.igs.umaryland.edu PMID:28095366

Multiscale structure and damage tolerance of coconut shells.

PubMed

Gludovatz, B; Walsh, F; Zimmermann, E A; Naleway, S E; Ritchie, R O; Kruzic, J J

2017-12-01

We investigated the endocarp of the fruit of Cocos nucifera (i.e., the inner coconut shell), examining the structure across multiple length scales through advanced characterization techniques and in situ testing of mechanical properties. Like many biological materials, the coconut shell possesses a hierarchical structure with distinct features at different length scales that depend on orientation and age. Aged coconut was found to have a significantly stronger (ultimate tensile strength, UTS = 48.5MPa), stiffer (Young's modulus, E = 1.92GPa), and tougher (fracture resistance (R-curve) peak of K J = 3.2MPa m 1/2 ) endocarp than the younger fruit for loading in the latitudinal orientation. While the mechanical properties of coconut shell were observed to improve with age, they also become more anisotropic: the young coconut shell had the same strength (17MPa) and modulus (0.64GPa) values and similar R-curves for both longitudinal and latitudinal loading configurations, whereas the old coconut had 82% higher strength for loading in the latitudinal orientation, and >50% higher crack growth toughness for cracking on the latitudinal plane. Structural aspects affecting the mechanical properties across multiple length scales with aging were identified as improved load transfer to the cellulose crystalline nanostructure (identified by synchrotron x-ray diffraction) and sclerification of the endocarp, the latter of which included closing of the cell lumens and lignification of the cell walls. The structural changes gave a denser and mechanically superior micro and nanostructure to the old coconut shell. Additionally, the development of anisotropy was attributed to the formation of an anisotropic open channel structure throughout the shell of the old coconut that affected both crack initiation during uniaxial tensile tests and the toughening mechanisms of crack trapping and deflection during crack propagation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Allostatic load and biological anthropology.

PubMed

Edes, Ashley N; Crews, Douglas E

2017-01-01

Multiple stressors affect developing and adult organisms, thereby partly structuring their phenotypes. Determining how stressors influence health, well-being, and longevity in human and nonhuman primate populations are major foci within biological anthropology. Although much effort has been devoted to examining responses to multiple environmental and sociocultural stressors, no holistic metric to measure stress-related physiological dysfunction has been widely applied within biological anthropology. Researchers from disciplines outside anthropology are using allostatic load indices (ALIs) to estimate such dysregulation and examine life-long outcomes of stressor exposures, including morbidity and mortality. Following allostasis theory, allostatic load represents accumulated physiological and somatic damage secondary to stressors and senescent processes experienced over the lifespan. ALIs estimate this wear-and-tear using a composite of biomarkers representing neuroendocrine, cardiovascular, metabolic, and immune systems. Across samples, ALIs are associated significantly with multiple individual characteristics (e.g., age, sex, education, DNA variation) of interest within biological anthropology. They also predict future outcomes, including aspects of life history variation (e.g., survival, lifespan), mental and physical health, morbidity and mortality, and likely health disparities between groups, by stressor exposures, ethnicity, occupations, and degree of departure from local indigenous life ways and integration into external and commodified ones. ALIs also may be applied to similar stress-related research areas among nonhuman primates. Given the reports from multiple research endeavors, here we propose ALIs may be useful for assessing stressors, stress responses, and stress-related dysfunction, current and long-term cognitive function, health and well-being, and risk of early mortality across many research programs within biological anthropology. © 2017 American Association of Physical Anthropologists.

Conformational assembly and biological properties of collagen mimetic peptides and their thermally responsive polymer conjugates

NASA Astrophysics Data System (ADS)

Krishna, Ohm Divyam

2011-12-01

Collagens are one of the most abundant proteins found in body tissues and organs, endowing structural integrity, mechanical strength, and multiple biological functions. Destabilized collagen inside human body leads to various degenerative diseases (ex. osteoarthritis) and ageing. This has continued to motivate the design of synthetic peptides and bio-synthetic polypeptides to closely mimic the native collagens in terms of triple helix structure and stability, potential for higher order assembly, and biological properties. However, the widespread application of de novo collagens has been limited in part by the need for hydroxylated proline in the formation of stable triple helical structures. To address this continued need, a hydroxyproline-free, thermally stable collagen-mimetic peptide (CLP-Cys) was rationally designed via the incorporation of electrostatically stabilized amino acid triplets. CLP-Cys was synthesized via solid phase peptide synthesis. The formation and stability of the triple helical structure were indicated via circular dichroism (CD) experiments and confirmed via differential scanning calorimetry (DSC) results. CLP-Cys also self-assembled into nano-rods and micro-fibrils, as evidenced via a combination of dynamic light scattering and transmission electron microscopy. Given the high thermal stability and its propensity for higher-order assembly, CLP-Cys was further functionalized at both the ends with a thermally responsive polymer, poly(diethylene glycol methyl ether methacrylate), (PDEGMEMA) to synthesize a biohybrid triblock copolymer. The CD results indicated that the triple helical form is retained, the thermal unfolding is sustained and helix to coil transition is reversible in the triblock hybrid context. The LCST of PDEGMEMA homopolymer (26 °C) is increased (to 35 °C) upon conjugation to the hydrophilic collagen peptide domain. Further, a combination of static light scattering, Cryo-SEM, TEM and confocal microscopy elucidated that the collapse of the thermo-responsive polymer upon heating (to above the LCST) leads to the assembly of these hybrid materials as micrometer sized spheres. At 75 °C a morphological transformation from spheres to fibrils were observed. These studies provided unique perspectives about the impact of stimuli-responsive polymers and the triple-helix forming peptides on each other; and how temperature as a stimulus can be employed to sequentially guide the assembly. The development of self-assembling hybrid materials with multiple sensitivities to temperature would offer useful opportunities in the design of stimuli-responsive nano-materials. The CLP-Cys peptide sequence has been designed to incorporate biologically relevant amino acid triplets (GEKGER) and its positive impact was seen via recruitment of human mesenchymal stem cells (hMSCs) for adhesion, spreading and proliferation on CLP-Cys functionalized glass and hyaluronic acid based hydrogel surfaces. Therefore, the prospects of these materials in biomedical applications including wound healing and tissue engineering are promising.

A blueprint for the synthesis and characterisation of thin graphene oxide with controlled lateral dimensions for biomedicine

NASA Astrophysics Data System (ADS)

Filipe Rodrigues, Artur; Newman, Leon; Lozano, Neus; Mukherjee, Sourav P.; Fadeel, Bengt; Bussy, Cyrill; Kostarelos, Kostas

2018-07-01

Graphene-based materials (GBMs) have ignited a revolution in material science and technology, with electronic, optical and mechanical properties that are of relevant interest for a wide range of applications. To support the development of these enabling technologies, a global research effort has been invested to assess their hazard and biocompatibility. Different production methods have however generated a diverse collection of GBMs with different physicochemical properties, leading to a variety of biological outcomes that are still not fully understood. To better understand the biological interactions of GBMs with biological systems and allow the design of safer materials, a thorough physicochemical characterisation is therefore highly recommended. The aim of the present work was to produce a blueprint for the synthesis and characterisation of non-pyrogenic graphene oxide (GO) flakes with three different controlled lateral dimensions, which could be further used for either hazard assessment or biomedical proof-of-concept studies. A battery of techniques used to characterise the physicochemical properties of the GO samples included atomic force microscopy, transmission electron microscopy, Fourier-transformed infra-red spectroscopy, x-ray photoelectron spectroscopy and Raman spectroscopy. The combination of these different techniques confirmed that only the lateral dimension varied among the GO materials produced, without significant change in any other of their fundamental physicochemical properties, such as the thickness or surface chemistry. The proposed systematic approach in GO batch production for biology will hopefully contribute to a better understanding of the material properties that govern their interactions with biological systems and offer a blueprint towards standardisation of biologically relevant 2D materials.

Spectroscopic Characterization of Streptavidin Functionalized Quantum dots1

PubMed Central

Wu, Yang; Lopez, Gabriel P.; Sklar, Larry A.; Buranda, Tione

2007-01-01

The spectroscopic properties of quantum dots can be strongly influenced by the conditions of their synthesis. In this work we have characterized several spectroscopic properties of commercial, streptavidin functionalized quantum dots (QD525, lot#1005-0045 and QD585, Lot#0905-0031 from Invitrogen). This is the first step in the development of calibration beads, to be used in a generalizable quantification scheme of multiple fluorescent tags in flow cytometry or microscopy applications. We used light absorption, photoexcitation, and emission spectra, together with excited-state lifetime measurements to characterize their spectroscopic behavior, concentrating on the 400-500nm wavelength ranges that are important in biological applications. Our data show an anomalous dependence of emission spectrum, lifetimes, and quantum yield (QY) on excitation wavelength that is particularly pronounced in the QD525. For QD525, QY values ranged from 0.2 at 480nm excitation up to 0.4 at 450nm and down again to 0.15 at 350nm. For QD585, QY values were constant at 0.2 between 500nm and 400nm, but dropped to 0.1 at 350nm. We attribute the wavelength dependences to heterogeneity in size and surface defects in the QD525, consistent with characteristics previously described in the chemistry literature. The results are discussed in the context of bridging the gap between what is currently known in the physical chemistry literature of quantum dots, and the quantitative needs of assay development in biological applications. PMID:17368555

Behavioural divergence, interfertility and speciation: a review.

PubMed

Pillay, Neville; Rymer, Tasmin L

2012-11-01

Behavioural compatibility between mates is fundamental for maintaining species boundaries and is achieved through appropriate communication between males and females. A breakdown in communication will lead to behavioural divergence and reduced interfertility. In this review, we summarise the current knowledge on male signals and female perception of these signals, integrating the literature from several taxa. We advocate that signaller-perceiver coevolution, which is usually under strong stabilising selection to enable mating, forms the basis of species-specific mate recognition systems. The mechanisms (phylogeny, geography, ecology, biology) shaping signaller-perceiver systems are briefly discussed to demonstrate the factors underpinning the evolution of signaller-perceiver couplings. Since divergence and diversification of communication systems is driven by changes in the mechanical properties of sensory pathways and morphology of sensory organs, we highlight signal modalities (auditory, olfactory, visual, tactile) and their importance in communication, particularly in mate selection. Next, using available examples and generating a stylised model, we suggest how disruption (biological, ecological, stochastic) of signaller-perceiver systems drives behavioural divergence and consequently results in reduced interfertility and speciation. Future studies should adopt an integrative approach, combining multiple parameters (phylogeny, adaptive utility of communication systems, genetics and biomechanical/biochemical properties of signals and perception) to explore how disruption of signaller-perceiver systems results in behavioural divergence and reduced interfertility. Finally, we question the impact that rapid environmental change will have on disruption of communication systems, potentially interfering with signaller-perceiver couplings. Copyright © 2012 Elsevier B.V. All rights reserved.

Complex dielectric properties of anhydrous polycrystalline glucose in the terahertz region

NASA Astrophysics Data System (ADS)

Sun, P.; Liu, W.; Zou, Y.; Jia, Qiong Z.; Li, Jia Y.

2015-03-01

We utilized terahertz time-domain spectroscopy (THz-TDS) to investigate the complex dielectric properties of solid polycrystalline material of anhydrous glucose (D-(+)-glucose with purity >99.9%). THz transmission spectra of samples were measured from 0.2 to 2.2 THz. The samples were prepared into tablets with thicknesses of 0.362, 0.447, 0.504, 0.522 and 0.626 mm, respectively. The imaginary part of the complex dielectric function of polycrystalline glucose showed that there were multiple characteristic absorption peaks at 1.232, 1.445, 1.522, 1.608, 1.811 and 1.987 THz, respectively. Moreover, for a given characteristic absorption peak, the real part of the complex dielectric function showed anomalous dispersion within the full width half maximum (FWHM) of the absorption peak. Both finite difference time-domain (FDTD) numerical simulations and experimental results showed that the complex dielectric function of anhydrous polycrystalline glucose fits well with the Lorentz dielectric mode. The plasma oscillation frequency was below the frequency of the light waves suggesting that the light waves passed through the polycrystalline glucose tablets. Calculations based on density functional theory (DFT) showed that the characteristic absorption peaks of polycrystalline glucose originated mainly from collective intermolecular vibrations such as hydrogen bonds and crystal phonon modes. The THz radiation can excite the vibrational or rotational energy levels of the biological macromolecules. This leads to changes in their spatial configuration or interactions. This study showed that THz-TDS has potential applications in biological and pharmaceutical research and food industry.

Network-based integration of systems genetics data reveals pathways associated with lignocellulosic biomass accumulation and processing

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

Mizrachi, Eshchar; Verbeke, Lieven; Christie, Nanette

As a consequence of their remarkable adaptability, fast growth, and superior wood properties, eucalypt tree plantations have emerged as key renewable feedstocks (over 20 million ha globally) for the production of pulp, paper, bioenergy, and other lignocellulosic products. However, most biomass properties such as growth, wood density, and wood chemistry are complex traits that are hard to improve in long-lived perennials. Systems genetics, a process of harnessing multiple levels of component trait information (e.g., transcript, protein, and metabolite variation) in populations that vary in complex traits, has proven effective for dissecting the genetics and biology of such traits. We havemore » applied a network-based data integration (NBDI) method for a systems-level analysis of genes, processes and pathways underlying biomass and bioenergy-related traits using a segregating Eucalyptus hybrid population. We show that the integrative approach can link biologically meaningful sets of genes to complex traits and at the same time reveal the molecular basis of trait variation. Gene sets identified for related woody biomass traits were found to share regulatory loci, cluster in network neighborhoods, and exhibit enrichment for molecular functions such as xylan metabolism and cell wall development. These findings offer a framework for identifying the molecular underpinnings of complex biomass and bioprocessing-related traits. Furthermore, a more thorough understanding of the molecular basis of plant biomass traits should provide additional opportunities for the establishment of a sustainable bio-based economy.« less

Network-based integration of systems genetics data reveals pathways associated with lignocellulosic biomass accumulation and processing

DOE PAGES

Mizrachi, Eshchar; Verbeke, Lieven; Christie, Nanette; ...

2017-01-17

As a consequence of their remarkable adaptability, fast growth, and superior wood properties, eucalypt tree plantations have emerged as key renewable feedstocks (over 20 million ha globally) for the production of pulp, paper, bioenergy, and other lignocellulosic products. However, most biomass properties such as growth, wood density, and wood chemistry are complex traits that are hard to improve in long-lived perennials. Systems genetics, a process of harnessing multiple levels of component trait information (e.g., transcript, protein, and metabolite variation) in populations that vary in complex traits, has proven effective for dissecting the genetics and biology of such traits. We havemore » applied a network-based data integration (NBDI) method for a systems-level analysis of genes, processes and pathways underlying biomass and bioenergy-related traits using a segregating Eucalyptus hybrid population. We show that the integrative approach can link biologically meaningful sets of genes to complex traits and at the same time reveal the molecular basis of trait variation. Gene sets identified for related woody biomass traits were found to share regulatory loci, cluster in network neighborhoods, and exhibit enrichment for molecular functions such as xylan metabolism and cell wall development. These findings offer a framework for identifying the molecular underpinnings of complex biomass and bioprocessing-related traits. Furthermore, a more thorough understanding of the molecular basis of plant biomass traits should provide additional opportunities for the establishment of a sustainable bio-based economy.« less

Drifts in ADCC-related quality attributes of Herceptin®: Impact on development of a trastuzumab biosimilar.

PubMed

Kim, Seokkyun; Song, Jinsu; Park, Seungkyu; Ham, Sunyoung; Paek, Kyungyeol; Kang, Minjung; Chae, Yunjung; Seo, Heewon; Kim, Hyung-Chan; Flores, Michael

A biosimilar product needs to demonstrate biosimilarity to the originator reference product, and the quality profile of the latter should be monitored throughout the period of the biosimilar's development to match the quality attributes of the 2 products that relate to efficacy and safety. For the development of a biosimilar version of trastuzumab, the reference product, Herceptin®, was extensively characterized for the main physicochemical and biologic properties by standard or state-of-the-art analytical methods, using multiple lots expiring between March 2015 and December 2019. For lots with expiry dates up to July 2018, a high degree of consistency was observed for all the tested properties. However, among the lots expiring in August 2018 or later, a downward drift was observed in %afucose (G0+G1+G2). Furthermore, the upward drift of %high mannose (M5+M6) was observed in the lots with expiry dates from June 2019 to December 2019. As a result, the combination of %afucose and %high mannose showed 2 marked drifts in the lots with expiry dates from August 2018 to December 2019, which was supported by the similar trend of biologic data, such as FcγRIIIa binding and antibody-dependent cell-mediated cytotoxicity (ADCC) activity. Considering that ADCC is one of the clinically relevant mechanisms of action for trastuzumab, the levels of %afucose and %high mannose should be tightly monitored as critical quality attributes for biosimilar development of trastuzumab.

Drifts in ADCC-related quality attributes of Herceptin®: Impact on development of a trastuzumab biosimilar

PubMed Central

Kim, Seokkyun; Song, Jinsu; Park, Seungkyu; Ham, Sunyoung; Paek, Kyungyeol; Kang, Minjung; Chae, Yunjung; Seo, Heewon; Kim, Hyung-Chan; Flores, Michael

2017-01-01

ABSTRACT A biosimilar product needs to demonstrate biosimilarity to the originator reference product, and the quality profile of the latter should be monitored throughout the period of the biosimilar's development to match the quality attributes of the 2 products that relate to efficacy and safety. For the development of a biosimilar version of trastuzumab, the reference product, Herceptin®, was extensively characterized for the main physicochemical and biologic properties by standard or state-of-the-art analytical methods, using multiple lots expiring between March 2015 and December 2019. For lots with expiry dates up to July 2018, a high degree of consistency was observed for all the tested properties. However, among the lots expiring in August 2018 or later, a downward drift was observed in %afucose (G0+G1+G2). Furthermore, the upward drift of %high mannose (M5+M6) was observed in the lots with expiry dates from June 2019 to December 2019. As a result, the combination of %afucose and %high mannose showed 2 marked drifts in the lots with expiry dates from August 2018 to December 2019, which was supported by the similar trend of biologic data, such as FcγRIIIa binding and antibody-dependent cell-mediated cytotoxicity (ADCC) activity. Considering that ADCC is one of the clinically relevant mechanisms of action for trastuzumab, the levels of %afucose and %high mannose should be tightly monitored as critical quality attributes for biosimilar development of trastuzumab. PMID:28296619

Transplantation analysis of developmental mechanisms in Hydra.

PubMed

Shimizu, Hiroshi

2012-01-01

Since the pioneering work of Ethel Browne (1909) who demonstrated for the first time the concept of organizer activity, i.e. the potency of an apical Hydra tissue to induce a secondary axis when transplanted onto a host, Hydra flourished as a fruitful model system for developmental studies. Over the next 60 years this efficient transplantation approach identified graded biological activities along the body column of Hydra named Head Acti-vation and Head Inhibition. These properties inspired theoretical modelers including Lewis Wolpert, Alfred Gierer and Hans Meinhardt to propose models for morphogenesis, respectively the positional information (1969) and reaction-diffusion (1972) models. In 1973, Tsutomu Sugiyama and Toshitaka Fujisawa initiated in Mishima a unique project to analyze the properties of Hydra strains with distinct morphological and developmental characters. To this end, they collected in several areas of Japan multiple Hydra strains that they subsequently characterized and crossed. They also established a lateral transplantation strategy that was much more powerful than the previous ones, as it combined quantitative measurements with cellular analyses thanks to the chimera procedures developed by Campbell and colleagues. In-deed this approach provided a paradigm to quantify in any morphological phenotype the Head Activation and Head Inhibition levels along the body column. In this article, I review the various strains identified by Sugiyama and colleagues, the principles and the main results deduced from the quantitative lateral transplantation strategy. In addition, I briefly discuss the relevance of this approach in the era of molecular biology.

Network-based integration of systems genetics data reveals pathways associated with lignocellulosic biomass accumulation and processing.

PubMed

Mizrachi, Eshchar; Verbeke, Lieven; Christie, Nanette; Fierro, Ana C; Mansfield, Shawn D; Davis, Mark F; Gjersing, Erica; Tuskan, Gerald A; Van Montagu, Marc; Van de Peer, Yves; Marchal, Kathleen; Myburg, Alexander A

2017-01-31

As a consequence of their remarkable adaptability, fast growth, and superior wood properties, eucalypt tree plantations have emerged as key renewable feedstocks (over 20 million ha globally) for the production of pulp, paper, bioenergy, and other lignocellulosic products. However, most biomass properties such as growth, wood density, and wood chemistry are complex traits that are hard to improve in long-lived perennials. Systems genetics, a process of harnessing multiple levels of component trait information (e.g., transcript, protein, and metabolite variation) in populations that vary in complex traits, has proven effective for dissecting the genetics and biology of such traits. We have applied a network-based data integration (NBDI) method for a systems-level analysis of genes, processes and pathways underlying biomass and bioenergy-related traits using a segregating Eucalyptus hybrid population. We show that the integrative approach can link biologically meaningful sets of genes to complex traits and at the same time reveal the molecular basis of trait variation. Gene sets identified for related woody biomass traits were found to share regulatory loci, cluster in network neighborhoods, and exhibit enrichment for molecular functions such as xylan metabolism and cell wall development. These findings offer a framework for identifying the molecular underpinnings of complex biomass and bioprocessing-related traits. A more thorough understanding of the molecular basis of plant biomass traits should provide additional opportunities for the establishment of a sustainable bio-based economy.

Simultaneous measurement of the Young's modulus and the Poisson ratio of thin elastic layers.

PubMed

Gross, Wolfgang; Kress, Holger

2017-02-07

The behavior of cells and tissue is greatly influenced by the mechanical properties of their environment. For studies on the interactions between cells and soft matrices, especially those applying traction force microscopy the characterization of the mechanical properties of thin substrate layers is essential. Various techniques to measure the elastic modulus are available. Methods to accurately measure the Poisson ratio of such substrates are rare and often imply either a combination of multiple techniques or additional equipment which is not needed for the actual biological studies. Here we describe a novel technique to measure both parameters, the Youngs's modulus and the Poisson ratio in a single experiment. The technique requires only a standard inverted epifluorescence microscope. As a model system, we chose cross-linked polyacrylamide and poly-N-isopropylacrylamide hydrogels which are known to obey Hooke's law. We place millimeter-sized steel spheres on the substrates which indent the surface. The data are evaluated using a previously published model which takes finite thickness effects of the substrate layer into account. We demonstrate experimentally for the first time that the application of the model allows the simultaneous determination of both the Young's modulus and the Poisson ratio. Since the method is easy to adapt and comes without the need of special equipment, we envision the technique to become a standard tool for the characterization of substrates for a wide range of investigations of cell and tissue behavior in various mechanical environments as well as other samples, including biological materials.

Multifunctional Cationic Lipid-Based Nanoparticles Facilitate Endosomal Escape and Reduction-Triggered Cytosolic siRNA Release

PubMed Central

Gujrati, Maneesh; Malamas, Anthony; Shin, Tesia; Jin, Erlei; Sun, Lulu; Lu, Zheng-Rong

2015-01-01

Small interfering RNA (siRNA) has garnered much attention in recent years as a promising avenue for cancer gene therapy due to its ability to silence disease-related genes. Effective gene silencing is contingent upon the delivery of siRNA into the cytosol of target cells and requires the implementation of delivery systems possessing multiple functionalities to overcome delivery barriers. The present work explores the multifunctional properties and biological activity of a recently developed cationic lipid carrier, (1-aminoethyl)iminobis[N-(oleicylcysteinyl-1-amino-ethyl)propionamide]) (ECO). The physicochemical properties and biological activity of ECO/siRNA nanoparticles were assessed over a range of N/P ratios to optimize the formulation. Potent and sustained luciferase silencing in a U87 glioblastoma cell line was observed, even in the presence of serum proteins. ECO/siRNA nanoparticles exhibited pH-dependent membrane disruption at pH levels corresponding to various stages of the intracellular trafficking pathway. It was found that disulfide linkages created during nanoparticle formation enhanced the protection of siRNA from degradation and facilitated site-specific siRNA release in the cytosol by glutathione-mediated reduction. Confocal microscopy confirmed that ECO/siRNA nanoparticles readily escaped from late endosomes prior to cytosolic release of the siRNA cargo. These results demonstrate that the rationally designed multifunctionality of ECO/siRNA nanoparticles is critical for intracellular siRNA delivery and the continuing development of safe and effective delivery systems. PMID:25020033

Analysis of terahertz dielectric properties of pork tissue

NASA Astrophysics Data System (ADS)

Huang, Yuqing; Xie, Qiaoling; Sun, Ping

2017-10-01

Seeing that about 70% component of fresh biological tissues is water, many scientists try to use water models to describe the dielectric properties of biological tissues. The classical water dielectric models are Debye model, Double Debye model and Cole-Cole model. This work aims to determine a suitable model by comparing three models above with experimental data. These models are applied to fresh pork tissue. By means of least square method, the parameters of different models are fitted with the experimental data. Comparing different models on both dielectric function, the Cole-Cole model is verified the best to describe the experiments of pork tissue. The correction factor α of the Cole-Cole model is an important modification for biological tissues. So Cole-Cole model is supposed to be a priority selection to describe the dielectric properties for biological tissues in the terahertz range.

Effects of amendment of different biochars on soil physical and biological properties related to carbon mineralization

NASA Astrophysics Data System (ADS)

Zhang, Renduo; Zhu, Shuzhi; Ouyang, Lei

2014-05-01

Biochar addition to soils potentially affects various soil properties, and these effects are dependent on biochars derived from different feedstock materials and pyrolysis processes. The objective of this study was to investigate the effects of amendment of different biochars on soil physical and biological properties. Biochars were produced with dairy manure and woodchip at temperatures of 300, 500, and 700°C, respectively. Each biochar was mixed at 5% (w/w) with a forest soil and the mixture was incubated for 180 days, during which soil physical and biological properties, and soil respiration rates were measured. Results showed that the biochar addition significantly enhanced the formation of soil macroaggregates at the early incubation time. The biochar application significantly reduced soil bulk density, increased the amount of soil organic matter, and stimulated microbial activity and soil respiration rates at the early incubation stage. Biochar applications improved water retention capacity, with stronger effects by biochars produced at higher pyrolysis temperatures. At the same suction, the soil with woodchip biochars possessed higher water content than with the dairy manure biochars. Biochar addition significantly affected the soil physical and biological properties, which resulted in different soil carbon mineralization rates.

Systems cell biology

PubMed Central

Mast, Fred D.; Ratushny, Alexander V.

2014-01-01

Systems cell biology melds high-throughput experimentation with quantitative analysis and modeling to understand many critical processes that contribute to cellular organization and dynamics. Recently, there have been several advances in technology and in the application of modeling approaches that enable the exploration of the dynamic properties of cells. Merging technology and computation offers an opportunity to objectively address unsolved cellular mechanisms, and has revealed emergent properties and helped to gain a more comprehensive and fundamental understanding of cell biology. PMID:25225336

Interactome Networks and Human Disease

PubMed Central

Vidal, Marc; Cusick, Michael E.; Barabási, Albert-László

2011-01-01

Complex biological systems and cellular networks may underlie most genotype to phenotype relationships. Here we review basic concepts in network biology, discussing different types of interactome networks and the insights that can come from analyzing them. We elaborate on why interactome networks are important to consider in biology, how they can be mapped and integrated with each other, what global properties are starting to emerge from interactome network models, and how these properties may relate to human disease. PMID:21414488

Development of morphogen gradient: The role of dimension and discreteness

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

Teimouri, Hamid; Kolomeisky, Anatoly B.

2014-02-28

The fundamental processes of biological development are governed by multiple signaling molecules that create non-uniform concentration profiles known as morphogen gradients. It is widely believed that the establishment of morphogen gradients is a result of complex processes that involve diffusion and degradation of locally produced signaling molecules. We developed a multi-dimensional discrete-state stochastic approach for investigating the corresponding reaction-diffusion models. It provided a full analytical description for stationary profiles and for important dynamic properties such as local accumulation times, variances, and mean first-passage times. The role of discreteness in developing of morphogen gradients is analyzed by comparing with available continuummore » descriptions. It is found that the continuum models prediction about multiple time scales near the source region in two-dimensional and three-dimensional systems is not supported in our analysis. Using ideas that view the degradation process as an effective potential, the effect of dimensionality on establishment of morphogen gradients is also discussed. In addition, we investigated how these reaction-diffusion processes are modified with changing the size of the source region.« less

Diffusion of multiple species with excluded-volume effects.

PubMed

Bruna, Maria; Chapman, S Jonathan

2012-11-28

Stochastic models of diffusion with excluded-volume effects are used to model many biological and physical systems at a discrete level. The average properties of the population may be described by a continuum model based on partial differential equations. In this paper we consider multiple interacting subpopulations/species and study how the inter-species competition emerges at the population level. Each individual is described as a finite-size hard core interacting particle undergoing brownian motion. The link between the discrete stochastic equations of motion and the continuum model is considered systematically using the method of matched asymptotic expansions. The system for two species leads to a nonlinear cross-diffusion system for each subpopulation, which captures the enhancement of the effective diffusion rate due to excluded-volume interactions between particles of the same species, and the diminishment due to particles of the other species. This model can explain two alternative notions of the diffusion coefficient that are often confounded, namely collective diffusion and self-diffusion. Simulations of the discrete system show good agreement with the analytic results.

A Case Study into Microbial Genome Assembly Gap Sequences and Finishing Strategies.

PubMed

Utturkar, Sagar M; Klingeman, Dawn M; Hurt, Richard A; Brown, Steven D

2017-01-01

This study characterized regions of DNA which remained unassembled by either PacBio and Illumina sequencing technologies for seven bacterial genomes. Two genomes were manually finished using bioinformatics and PCR/Sanger sequencing approaches and regions not assembled by automated software were analyzed. Gaps present within Illumina assemblies mostly correspond to repetitive DNA regions such as multiple rRNA operon sequences. PacBio gap sequences were evaluated for several properties such as GC content, read coverage, gap length, ability to form strong secondary structures, and corresponding annotations. Our hypothesis that strong secondary DNA structures blocked DNA polymerases and contributed to gap sequences was not accepted. PacBio assemblies had few limitations overall and gaps were explained as cumulative effect of lower than average sequence coverage and repetitive sequences at contig termini. An important aspect of the present study is the compilation of biological features that interfered with assembly and included active transposons, multiple plasmid sequences, phage DNA integration, and large sequence duplication. Our targeted genome finishing approach and systematic evaluation of the unassembled DNA will be useful for others looking to close, finish, and polish microbial genome sequences.

Highly stable multi-anchored magnetic nanoparticles for optical imaging within biofilms

DOE PAGES

Stone, R. C.; Fellows, B. D.; Qi, B.; ...

2015-08-05

Magnetic nanoparticles are the next tool in medical diagnoses and treatment in many different biomedical applications, including magnetic hyperthermia as alternative treatment for cancer and bacterial infections, as well as the disruption of biofilms. The colloidal stability of the magnetic nanoparticles in a biological environment is crucial for efficient delivery. A surface that can be easily modifiable can also improve the delivery and imaging properties of the magnetic nanoparticle by adding targeting and imaging moieties, providing a platform for additional modification. The strategy presented in this paper includes multiple nitroDOPA anchors for robust binding to the surface tied to themore » same polymer backbone as multiple poly(ethylene oxide) chains for steric stability. This approach provides biocompatibility and enhanced stability in fetal bovine serum (FBS) and phosphate buffer saline (PBS). As a proof of concept, these polymer-particles complexes were then modified with a near infrared dye and utilized in characterizing the integration of magnetic nanoparticles in biofilms. Finally, the work presented in this manuscript describes the synthesis and characterization of a nontoxic platform for the labeling of near IR-dyes for bioimaging.« less

Laser surface texturing of polymers for biomedical applications

NASA Astrophysics Data System (ADS)

Riveiro, Antonio; Maçon, Anthony L. B.; del Val, Jesus; Comesaña, Rafael; Pou, Juan

2018-02-01

Polymers are materials widely used in biomedical science because of their biocompatibility, and good mechanical properties (which, in some cases, are similar to those of human tissues); however, these materials are, in general, chemically and biologically inert. Surface characteristics, such as topography (at the macro-, micro, and nanoscale), surface chemistry, surface energy, charge or wettability are interrelated properties, and they cooperatively influence the biological performance of materials when used for biomedical applications. They regulate the biological response at the implant/tissue interface (e.g., influencing the cell adhesion, cell orientation, cell motility, etc.). Several surface processing techniques have been explored to modulate these properties for biomedical applications. Despite their potentials, these methods have limitations that prevent their applicability. In this regard, laser-based methods, in particular laser surface texturing (LST), can be an interesting alternative. Different works have showed the potentiality of this technique to control the surface properties of biomedical polymers and enhance their biological performance; however, more research is needed to obtain the desired biological response. This work provides a general overview of the basics and applications of LST for the surface modification of polymers currently used in the clinical practice (e.g. PEEK, UHMWPE, PP, etc.). The modification of roughness, wettability, and their impact on the biological response is addressed to offer new insights on the surface modification of biomedical polymers.

Optimization of the Inverse Algorithm for Estimating the Optical Properties of Biological Materials Using Spatially-resolved Diffuse Reflectance Technique

USDA-ARS?s Scientific Manuscript database

Determination of the optical properties from intact biological materials based on diffusion approximation theory is a complicated inverse problem, and it requires proper implementation of inverse algorithm, instrumentation, and experiment. This work was aimed at optimizing the procedure of estimatin...

CARBON LOSS AND OPTICAL PROPERTY CHANGES DURING LONG-TERM PHOTOCHEMICAL AND BIOLOGICAL DEGRADATION OF ESTUARINE DISSOLVED ORGANIC MATTER

EPA Science Inventory

Terrestrially derived dissolved organic matter (DOM) impacts the optical properties of coastal seawater and affects carbon cycling on a global scale. We studied sequential long-term photochemical and biological degradation of estuarine dissolved organic matter from the
Satilla...

Improved algorithm for estimating optical properties of food and biological materials using spatially-resolved diffuse reflectance

USDA-ARS?s Scientific Manuscript database

In this research, the inverse algorithm for estimating optical properties of food and biological materials from spatially-resolved diffuse reflectance was optimized in terms of data smoothing, normalization and spatial region of reflectance profile for curve fitting. Monte Carlo simulation was used ...

Rheological properties of a biological thermo-responsive hydrogel produced from soybean oil polymers

USDA-ARS?s Scientific Manuscript database

The rheological properties of a newly developed biological thermo-hydrogel made from vegetable oil were investigated. The material named HPSO-VI is a hydrolytic product of polymerized soybean oil (PSO). HPSO-VI exhibited viscoelastic behavior above 2% (wt. %) at room temperature and viscous fluid ...

Rheological Properties of a Biological Thermo-Hydrogel Produced from Soybean Oil Polymers

USDA-ARS?s Scientific Manuscript database

The rheological properties of a newly developed biological thermo-hydrogel made from vegetable oil were investigated. The material named HPSO-HG is a hydrolytic product of polymerized soybean oil (PSO). HPSO-HG exhibited viscoelastic behavior above 2% (wt.%) at room temperature and viscous fluid b...

Exploring the Factors Related to Acceptance of Evolutionary Theory among Turkish Preservice Biology Teachers: Toward a More Informative Conceptual Ecology for Biological Evolution

ERIC Educational Resources Information Center

Deniz, Hasan; Donnelly, Lisa A.; Yilmaz, Irfan

2008-01-01

In this study, using multiple regression analysis, we aimed to explore the factors related to acceptance of evolutionary theory among preservice Turkish biology teachers using conceptual ecology for biological evolution as a theoretical lens. We aimed to determine the extent to which we can account for the variance in acceptance of evolutionary…

Thinking Like a Wolf, a Sheep, or a Firefly: Learning Biology through Constructing and Testing Computational Theories--An Embodied Modeling Approach

ERIC Educational Resources Information Center

Wilensky, Uri; Reisman, Kenneth

2006-01-01

Biological phenomena can be investigated at multiple levels, from the molecular to the cellular to the organismic to the ecological. In typical biology instruction, these levels have been segregated. Yet, it is by examining the connections between such levels that many phenomena in biology, and complex systems in general, are best explained. We…

Towards a unified theory of neocortex: laminar cortical circuits for vision and cognition.

PubMed

Grossberg, Stephen

2007-01-01

A key goal of computational neuroscience is to link brain mechanisms to behavioral functions. The present article describes recent progress towards explaining how laminar neocortical circuits give rise to biological intelligence. These circuits embody two new and revolutionary computational paradigms: Complementary Computing and Laminar Computing. Circuit properties include a novel synthesis of feedforward and feedback processing, of digital and analog processing, and of preattentive and attentive processing. This synthesis clarifies the appeal of Bayesian approaches but has a far greater predictive range that naturally extends to self-organizing processes. Examples from vision and cognition are summarized. A LAMINART architecture unifies properties of visual development, learning, perceptual grouping, attention, and 3D vision. A key modeling theme is that the mechanisms which enable development and learning to occur in a stable way imply properties of adult behavior. It is noted how higher-order attentional constraints can influence multiple cortical regions, and how spatial and object attention work together to learn view-invariant object categories. In particular, a form-fitting spatial attentional shroud can allow an emerging view-invariant object category to remain active while multiple view categories are associated with it during sequences of saccadic eye movements. Finally, the chapter summarizes recent work on the LIST PARSE model of cognitive information processing by the laminar circuits of prefrontal cortex. LIST PARSE models the short-term storage of event sequences in working memory, their unitization through learning into sequence, or list, chunks, and their read-out in planned sequential performance that is under volitional control. LIST PARSE provides a laminar embodiment of Item and Order working memories, also called Competitive Queuing models, that have been supported by both psychophysical and neurobiological data. These examples show how variations of a common laminar cortical design can embody properties of visual and cognitive intelligence that seem, at least on the surface, to be mechanistically unrelated.

OpenBiodiv-O: ontology of the OpenBiodiv knowledge management system.

PubMed

Senderov, Viktor; Simov, Kiril; Franz, Nico; Stoev, Pavel; Catapano, Terry; Agosti, Donat; Sautter, Guido; Morris, Robert A; Penev, Lyubomir

2018-01-18

The biodiversity domain, and in particular biological taxonomy, is moving in the direction of semantization of its research outputs. The present work introduces OpenBiodiv-O, the ontology that serves as the basis of the OpenBiodiv Knowledge Management System. Our intent is to provide an ontology that fills the gaps between ontologies for biodiversity resources, such as DarwinCore-based ontologies, and semantic publishing ontologies, such as the SPAR Ontologies. We bridge this gap by providing an ontology focusing on biological taxonomy. OpenBiodiv-O introduces classes, properties, and axioms in the domains of scholarly biodiversity publishing and biological taxonomy and aligns them with several important domain ontologies (FaBiO, DoCO, DwC, Darwin-SW, NOMEN, ENVO). By doing so, it bridges the ontological gap across scholarly biodiversity publishing and biological taxonomy and allows for the creation of a Linked Open Dataset (LOD) of biodiversity information (a biodiversity knowledge graph) and enables the creation of the OpenBiodiv Knowledge Management System. A key feature of the ontology is that it is an ontology of the scientific process of biological taxonomy and not of any particular state of knowledge. This feature allows it to express a multiplicity of scientific opinions. The resulting OpenBiodiv knowledge system may gain a high level of trust in the scientific community as it does not force a scientific opinion on its users (e.g. practicing taxonomists, library researchers, etc.), but rather provides the tools for experts to encode different views as science progresses. OpenBiodiv-O provides a conceptual model of the structure of a biodiversity publication and the development of related taxonomic concepts. It also serves as the basis for the OpenBiodiv Knowledge Management System.

Comparative study of binding interactions between porphyrin systems and aromatic compounds of biological importance by multiple spectroscopic techniques: A review

NASA Astrophysics Data System (ADS)

Makarska-Bialokoz, Magdalena

2018-07-01

The specific spectroscopic and redox properties of porphyrins predestine them to fulfill the role of sensors during interacting with different biologically active substances. Monitoring of binding interactions in the systems porphyrin-biologically active compound is a key question not only in the field of physiological functions of living organisms, but also in environmental protection, notably in the light of the rapidly growing drug consumption and concurrently the production of drug effluents. Not always beneficial action of drugs on natural porphyrin systems induces to further studies, with commercially available porphyrins as the model systems. Therefore the binding process between several water-soluble porphyrins and a series of biologically active compounds (e.g. caffeine, guanine, theophylline, theobromine, xanthine, uric acid) has been studied in different aqueous solutions analyzing their absorption and steady-state fluorescence spectra, the porphyrin fluorescence lifetimes and their quantum yields. The magnitude of the binding and fluorescence quenching constants values for particular quenchers decreases in a series: uric acid > guanine > caffeine > theophylline > theobromine > xanthine. In all the systems studied there are characters of static quenching, as a consequence of the π-π-stacked non-covalent and non-fluorescent complexes formation between porphyrins and interacting compounds, accompanied simultaneously by the additional specific binding interactions. The porphyrin fluorescence quenching can be explain by the photoinduced intermolecular electron transfer from aromatic compound to the center of the porphyrin molecule, playing the role of the binding site. Presented results can be valuable for designing of new fluorescent porphyrin chemosensors or monitoring of drug traces in aqueous solutions. The obtained outcomes have also the toxicological and medical importance, providing insight into the interactions of the water-soluble porphyrins with biologically active substances.

Systems biology impact on antiepileptic drug discovery.

PubMed

Margineanu, Doru Georg

2012-02-01

Systems biology (SB), a recent trend in bioscience research to consider the complex interactions in biological systems from a holistic perspective, sees the disease as a disturbed network of interactions, rather than alteration of single molecular component(s). SB-relying network pharmacology replaces the prevailing focus on specific drug-receptor interaction and the corollary of rational drug design of "magic bullets", by the search for multi-target drugs that would act on biological networks as "magic shotguns". Epilepsy being a multi-factorial, polygenic and dynamic pathology, SB approach appears particularly fit and promising for antiepileptic drug (AED) discovery. In fact, long before the advent of SB, AED discovery already involved some SB-like elements. A reported SB project aimed to find out new drug targets in epilepsy relies on a relational database that integrates clinical information, recordings from deep electrodes and 3D-brain imagery with histology and molecular biology data on modified expression of specific genes in the brain regions displaying spontaneous epileptic activity. Since hitting a single target does not treat complex diseases, a proper pharmacological promiscuity might impart on an AED the merit of being multi-potent. However, multi-target drug discovery entails the complicated task of optimizing multiple activities of compounds, while having to balance drug-like properties and to control unwanted effects. Specific design tools for this new approach in drug discovery barely emerge, but computational methods making reliable in silico predictions of poly-pharmacology did appear, and their progress might be quite rapid. The current move away from reductionism into network pharmacology allows expecting that a proper integration of the intrinsic complexity of epileptic pathology in AED discovery might result in literally anti-epileptic drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

Purification and biological characterization of soluble, recombinant mouse IFNβ expressed in insect cells.

PubMed

Stifter, Sebastian A; Gould, Jodee A; Mangan, Niamh E; Reid, Hugh H; Rossjohn, Jamie; Hertzog, Paul J; de Weerd, Nicole A

2014-02-01

Interferon β (IFNβ) is a member of the type I interferon family of cytokines widely recognised for their anti-viral, anti-proliferative and immunomodulatory properties. Recombinant, biologically active forms of this cytokine are used clinically for the treatment of multiple sclerosis and in laboratories to study the role of this cytokine in health and disease. Established methods for expression of IFNβ utilise either bacterial systems from which the insoluble recombinant proteins must be refolded, or mammalian expression systems in which large volumes of cell culture are required for recovery of acceptable yields. Utilising the baculovirus expression system and Trichoplusia ni (Cabbage Looper) BTI-TN-5B1-4 cell line, we report a reproducible method for production and purification of milligram/litre quantities of biologically active murine IFNβ. Due to the design of our construct and the eukaryotic nature of insect cells, the resulting soluble protein is secreted allowing purification of the Histidine-tagged natively-folded protein from the culture supernatant. The IFNβ purification method described is a two-step process employing immobilised metal-ion affinity chromatography (IMAC) and reverse-phase high performance liquid chromatography (RP-HPLC) that results in production of significantly more purified IFNβ than any other reported eukaryotic-based expression system. Recombinant murine IFNβ produced by this method was natively folded and demonstrated hallmark type I interferon biological effects including antiviral and anti-proliferative activities, and induced genes characteristic of IFNβ activity in vivo. Recombinant IFNβ also had specific activity levels exceeding that of the commercially available equivalent. Together, our findings provide a method for production of highly pure, biologically active murine IFNβ. Copyright © 2013 Elsevier Inc. All rights reserved.

Multiple-Swarm Ensembles: Improving the Predictive Power and Robustness of Predictive Models and Its Use in Computational Biology.

PubMed

Alves, Pedro; Liu, Shuang; Wang, Daifeng; Gerstein, Mark

2018-01-01

Machine learning is an integral part of computational biology, and has already shown its use in various applications, such as prognostic tests. In the last few years in the non-biological machine learning community, ensembling techniques have shown their power in data mining competitions such as the Netflix challenge; however, such methods have not found wide use in computational biology. In this work, we endeavor to show how ensembling techniques can be applied to practical problems, including problems in the field of bioinformatics, and how they often outperform other machine learning techniques in both predictive power and robustness. Furthermore, we develop a methodology of ensembling, Multi-Swarm Ensemble (MSWE) by using multiple particle swarm optimizations and demonstrate its ability to further enhance the performance of ensembles.

Identification of nanoparticles and nanosystems in biological matrices with scanning probe microscopy.

PubMed

Angeloni, Livia; Reggente, Melania; Passeri, Daniele; Natali, Marco; Rossi, Marco

2018-04-17

Identification of nanoparticles and nanosystems into cells and biological matrices is a hot research topic in nanobiotechnologies. Because of their capability to map physical properties (mechanical, electric, magnetic, chemical, or optical), several scanning probe microscopy based techniques have been proposed for the subsurface detection of nanomaterials in biological systems. In particular, atomic force microscopy (AFM) can be used to reveal stiff nanoparticles in cells and other soft biomaterials by probing the sample mechanical properties through the acquisition of local indentation curves or through the combination of ultrasound-based methods, like contact resonance AFM (CR-AFM) or scanning near field ultrasound holography. Magnetic force microscopy can detect magnetic nanoparticles and other magnetic (bio)materials in nonmagnetic biological samples, while electric force microscopy, conductive AFM, and Kelvin probe force microscopy can reveal buried nanomaterials on the basis of the differences between their electric properties and those of the surrounding matrices. Finally, scanning near field optical microscopy and tip-enhanced Raman spectroscopy can visualize buried nanostructures on the basis of their optical and chemical properties. Despite at a still early stage, these methods are promising for detection of nanomaterials in biological systems as they could be truly noninvasive, would not require destructive and time-consuming specific sample preparation, could be performed in vitro, on alive samples and in water or physiological environment, and by continuously imaging the same sample could be used to dynamically monitor the diffusion paths and interaction mechanisms of nanomaterials into cells and biological systems. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology. © 2018 Wiley Periodicals, Inc.

Development of a Biological Science Quantitative Reasoning Exam (BioSQuaRE)

ERIC Educational Resources Information Center

Stanhope, Liz; Ziegler, Laura; Haque, Tabassum; Le, Laura; Vinces, Marcelo; Davis, Gregory K.; Zieffler, Andrew; Brodfuehrer, Peter; Preest, Marion; Belitsky, Jason M.; Umbanhowar, Charles, Jr.; Overvoorde, Paul J.

2017-01-01

Multiple reports highlight the increasingly quantitative nature of biological research and the need to innovate means to ensure that students acquire quantitative skills. We present a tool to support such innovation. The Biological Science Quantitative Reasoning Exam (BioSQuaRE) is an assessment instrument designed to measure the quantitative…

Interdisciplinary Lessons for the Teaching of Biology from the Practice of Evo-Devo

ERIC Educational Resources Information Center

Love, Alan C.

2013-01-01

Evolutionary developmental biology (Evo-devo) is a vibrant area of contemporary life science that should be (and is) increasingly incorporated into teaching curricula. Although the inclusion of this content is important for biological pedagogy at multiple levels of instruction, there are also philosophical lessons that can be drawn from the…

Cytokines as endogenous pyrogens.

PubMed

Dinarello, C A

1999-03-01

Cytokines are pleiotropic molecules mediating several pathologic processes. Long before the discovery of cytokines as immune system growth factors or as bone marrow stimulants, investigators learned a great deal about cytokines when they studied them as the endogenous mediators of fever. The terms "granulocytic" or "endogenous pyrogen" were used to describe substances with the biologic property of fever induction. Today, we recognize that pyrogenicity is a fundamental biologic property of several cytokines and hence the clinically recognizeable property of fever links host perturbations during disease with fundamental perturbations in cell biology. In this review, the discoveries made on endogenous pyrogens are revisited, with insights into the importance of the earlier work to the present-day understanding of cytokines in health and in disease.