Strategies for Directing the Structure and Function of 3D Collagen Biomaterials across Length Scales

PubMed Central

Walters, Brandan D.; Stegemann, Jan P.

2013-01-01

Collagen type I is a widely used natural biomaterial that has found utility in a variety of biological and medical applications. Its well characterized structure and role as an extracellular matrix protein make it a highly relevant material for controlling cell function and mimicking tissue properties. Collagen type I is abundant in a number of tissues, and can be isolated as a purified protein. This review focuses on hydrogel biomaterials made by reconstituting collagen type I from a solubilized form, with an emphasis on in vitro studies in which collagen structure can be controlled. The hierarchical structure of collagen from the nanoscale to the macroscale is described, with an emphasis on how structure is related to function across scales. Methods of reconstituting collagen into hydrogel materials are presented, including molding of macroscopic constructs, creation of microscale modules, and electrospinning of nanoscale fibers. The modification of collagen biomaterials to achieve desired structures and functions is also addressed, with particular emphasis on mechanical control of collagen structure, creation of collagen composite materials, and crosslinking of collagenous matrices. Biomaterials scientists have made remarkable progress in rationally designing collagen-based biomaterials and in applying them to both the study of biology and for therapeutic benefit. This broad review illustrates recent examples of techniques used to control collagen structure, and to thereby direct its biological and mechanical functions. PMID:24012608

Precision control of recombinant gene transcription for CHO cell synthetic biology.

PubMed

Brown, Adam J; James, David C

2016-01-01

The next generation of mammalian cell factories for biopharmaceutical production will be genetically engineered to possess both generic and product-specific manufacturing capabilities that may not exist naturally. Introduction of entirely new combinations of synthetic functions (e.g. novel metabolic or stress-response pathways), and retro-engineering of existing functional cell modules will drive disruptive change in cellular manufacturing performance. However, before we can apply the core concepts underpinning synthetic biology (design, build, test) to CHO cell engineering we must first develop practical and robust enabling technologies. Fundamentally, we will require the ability to precisely control the relative stoichiometry of numerous functional components we simultaneously introduce into the host cell factory. In this review we discuss how this can be achieved by design of engineered promoters that enable concerted control of recombinant gene transcription. We describe the specific mechanisms of transcriptional regulation that affect promoter function during bioproduction processes, and detail the highly-specific promoter design criteria that are required in the context of CHO cell engineering. The relative applicability of diverse promoter development strategies are discussed, including re-engineering of natural sequences, design of synthetic transcription factor-based systems, and construction of synthetic promoters. This review highlights the potential of promoter engineering to achieve precision transcriptional control for CHO cell synthetic biology. Copyright © 2015. Published by Elsevier Inc.

The structure of a gene co-expression network reveals biological functions underlying eQTLs.

PubMed

Villa-Vialaneix, Nathalie; Liaubet, Laurence; Laurent, Thibault; Cherel, Pierre; Gamot, Adrien; SanCristobal, Magali

2013-01-01

What are the commonalities between genes, whose expression level is partially controlled by eQTL, especially with regard to biological functions? Moreover, how are these genes related to a phenotype of interest? These issues are particularly difficult to address when the genome annotation is incomplete, as is the case for mammalian species. Moreover, the direct link between gene expression and a phenotype of interest may be weak, and thus difficult to handle. In this framework, the use of a co-expression network has proven useful: it is a robust approach for modeling a complex system of genetic regulations, and to infer knowledge for yet unknown genes. In this article, a case study was conducted with a mammalian species. It showed that the use of a co-expression network based on partial correlation, combined with a relevant clustering of nodes, leads to an enrichment of biological functions of around 83%. Moreover, the use of a spatial statistics approach allowed us to superimpose additional information related to a phenotype; this lead to highlighting specific genes or gene clusters that are related to the network structure and the phenotype. Three main results are worth noting: first, key genes were highlighted as a potential focus for forthcoming biological experiments; second, a set of biological functions, which support a list of genes under partial eQTL control, was set up by an overview of the global structure of the gene expression network; third, pH was found correlated with gene clusters, and then with related biological functions, as a result of a spatial analysis of the network topology.

Fabrication, Characterization, and Biological Activity of Avermectin Nano-delivery Systems with Different Particle Sizes

NASA Astrophysics Data System (ADS)

Wang, Anqi; Wang, Yan; Sun, Changjiao; Wang, Chunxin; Cui, Bo; Zhao, Xiang; Zeng, Zhanghua; Yao, Junwei; Yang, Dongsheng; Liu, Guoqiang; Cui, Haixin

2018-01-01

Nano-delivery systems for the active ingredients of pesticides can improve the utilization rates of pesticides and prolong their control effects. This is due to the nanocarrier envelope and controlled release function. However, particles containing active ingredients in controlled release pesticide formulations are generally large and have wide size distributions. There have been limited studies about the effect of particle size on the controlled release properties and biological activities of pesticide delivery systems. In the current study, avermectin (Av) nano-delivery systems were constructed with different particle sizes and their performances were evaluated. The Av release rate in the nano-delivery system could be effectively controlled by changing the particle size. The biological activity increased with decreasing particle size. These results suggest that Av nano-delivery systems can significantly improve the controllable release, photostability, and biological activity, which will improve efficiency and reduce pesticide residues.

End-to-end automated microfluidic platform for synthetic biology: from design to functional analysis

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

Linshiz, Gregory; Jensen, Erik; Stawski, Nina

Synthetic biology aims to engineer biological systems for desired behaviors. The construction of these systems can be complex, often requiring genetic reprogramming, extensive de novo DNA synthesis, and functional screening. Here, we present a programmable, multipurpose microfluidic platform and associated software and apply the platform to major steps of the synthetic biology research cycle: design, construction, testing, and analysis. We show the platform’s capabilities for multiple automated DNA assembly methods, including a new method for Isothermal Hierarchical DNA Construction, and for Escherichia coli and Saccharomyces cerevisiae transformation. The platform enables the automated control of cellular growth, gene expression induction, andmore » proteogenic and metabolic output analysis. Finally, taken together, we demonstrate the microfluidic platform’s potential to provide end-to-end solutions for synthetic biology research, from design to functional analysis.« less

End-to-end automated microfluidic platform for synthetic biology: from design to functional analysis

DOE PAGES

Linshiz, Gregory; Jensen, Erik; Stawski, Nina; ...

2016-02-02

Synthetic biology aims to engineer biological systems for desired behaviors. The construction of these systems can be complex, often requiring genetic reprogramming, extensive de novo DNA synthesis, and functional screening. Here, we present a programmable, multipurpose microfluidic platform and associated software and apply the platform to major steps of the synthetic biology research cycle: design, construction, testing, and analysis. We show the platform’s capabilities for multiple automated DNA assembly methods, including a new method for Isothermal Hierarchical DNA Construction, and for Escherichia coli and Saccharomyces cerevisiae transformation. The platform enables the automated control of cellular growth, gene expression induction, andmore » proteogenic and metabolic output analysis. Finally, taken together, we demonstrate the microfluidic platform’s potential to provide end-to-end solutions for synthetic biology research, from design to functional analysis.« less

Assessment and management of soil microbial community structure for disease suppression.

PubMed

Mazzola, Mark

2004-01-01

Identification of the biological properties contributing to the function of suppressive soils is a necessary first step to the management of such systems for use in the control of soilborne diseases. The development and application of molecular methods for the characterization and monitoring of soil microbial properties will enable a more rapid and detailed assessment of the biological nature of soil suppressiveness. Although suppressive soils have provided a wealth of microbial resources that have subsequently been applied for the biological control of soilborne plant pathogens, the full functional capabilities of the phenomena have not been realized in production agricultural ecosystems. Cultural practices, such as the application of soil amendments, have the capacity to enhance disease suppression, though the biological modes of action may vary from that initially resident to the soil. Plants have a distinct impact on characteristics and activity of resident soil microbial communities, and therefore play an important role in determining the development of the disease-suppressive state. Likewise, plant genotype will modulate these same biological communities, and should be considered when developing strategies to exploit the potential of such a natural disease control system. Implementation of consistently effective practices to manage this resource in an economically and environmentally feasible manner will require more detailed investigation of these biologically complex systems and refinement of currently available methodologies.

Nanomaterial interactions with biomembranes: Bridging the gap between soft matter models and biological context.

PubMed

Werner, Marco; Auth, Thorsten; Beales, Paul A; Fleury, Jean Baptiste; Höök, Fredrik; Kress, Holger; Van Lehn, Reid C; Müller, Marcus; Petrov, Eugene P; Sarkisov, Lev; Sommer, Jens-Uwe; Baulin, Vladimir A

2018-04-03

Synthetic polymers, nanoparticles, and carbon-based materials have great potential in applications including drug delivery, gene transfection, in vitro and in vivo imaging, and the alteration of biological function. Nature and humans use different design strategies to create nanomaterials: biological objects have emerged from billions of years of evolution and from adaptation to their environment resulting in high levels of structural complexity; in contrast, synthetic nanomaterials result from minimalistic but controlled design options limited by the authors' current understanding of the biological world. This conceptual mismatch makes it challenging to create synthetic nanomaterials that possess desired functions in biological media. In many biologically relevant applications, nanomaterials must enter the cell interior to perform their functions. An essential transport barrier is the cell-protecting plasma membrane and hence the understanding of its interaction with nanomaterials is a fundamental task in biotechnology. The authors present open questions in the field of nanomaterial interactions with biological membranes, including: how physical mechanisms and molecular forces acting at the nanoscale restrict or inspire design options; which levels of complexity to include next in computational and experimental models to describe how nanomaterials cross barriers via passive or active processes; and how the biological media and protein corona interfere with nanomaterial functionality. In this Perspective, the authors address these questions with the aim of offering guidelines for the development of next-generation nanomaterials that function in biological media.

[Topical issues of biological safety under current conditions. Part 3. Scientific provision for the national regulation of the biological safety framework in its broad interpretation].

PubMed

Onishchenko, G G; Smolensky, V Yu; Ezhlova, E B; Demina, Yu V; Toporkov, V P; Toporkov, A V; Lyapin, M N; Kutyrev, V V

2014-01-01

Consequent of investigation concerned with biological safety (BS) framework development in its broad interpretation, reflected in the Russian Federation State Acts, identified have been conceptual entity parameters of the up-to-date broad interpretation of BS, which have formed a part of the developed by the authors system for surveillance (prophylaxis, localization, indication, identification, and diagnostics) and control (prophylaxis, localization, and response/elimination) over the emergency situations of biological (sanitary-epidemiological) character. The System functionality is activated through supplying the content with information data which are concerned with monitoring and control of specific internal and external threats in the sphere of BS provision fixed in the Supplement 2 of the International Health Regulations (IHR, 2005), and with the previously characterized nomenclature of hazardous biological factors. The system is designed as a network-based research-and-practice tool for evaluation of the situation in the sphere of BS provision, as well as assessment of efficacy of management decision making as regards BS control and proper State policy implementation. Most of the system elements either directly or indirectly relate to the scope of activities conducted by Federal Service for Surveillance in the Sphere of Consumers Rights Protection and Human Welfare, being substantial argument for allocating coordination functions in the sphere of BS provision to this government agency and consistent with its function as the State Coordinator on IHR (2005). The data collected serve as materials to Draft Federal Law "Concerning biological safety provision of the population".

Towards Engineering Biological Systems in a Broader Context.

PubMed

Venturelli, Ophelia S; Egbert, Robert G; Arkin, Adam P

2016-02-27

Significant advances have been made in synthetic biology to program information processing capabilities in cells. While these designs can function predictably in controlled laboratory environments, the reliability of these devices in complex, temporally changing environments has not yet been characterized. As human society faces global challenges in agriculture, human health and energy, synthetic biology should develop predictive design principles for biological systems operating in complex environments. Natural biological systems have evolved mechanisms to overcome innumerable and diverse environmental challenges. Evolutionary design rules should be extracted and adapted to engineer stable and predictable ecological function. We highlight examples of natural biological responses spanning the cellular, population and microbial community levels that show promise in synthetic biology contexts. We argue that synthetic circuits embedded in host organisms or designed ecologies informed by suitable measurement of biotic and abiotic environmental parameters could be used as engineering substrates to achieve target functions in complex environments. Successful implementation of these methods will broaden the context in which synthetic biological systems can be applied to solve important problems. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

From noise to synthetic nucleoli: can synthetic biology achieve new insights?

PubMed

Ciechonska, Marta; Grob, Alice; Isalan, Mark

2016-04-18

Synthetic biology aims to re-organise and control biological components to make functional devices. Along the way, the iterative process of designing and testing gene circuits has the potential to yield many insights into the functioning of the underlying chassis of cells. Thus, synthetic biology is converging with disciplines such as systems biology and even classical cell biology, to give a new level of predictability to gene expression, cell metabolism and cellular signalling networks. This review gives an overview of the contributions that synthetic biology has made in understanding gene expression, in terms of cell heterogeneity (noise), the coupling of growth and energy usage to expression, and spatiotemporal considerations. We mainly compare progress in bacterial and mammalian systems, which have some of the most-developed engineering frameworks. Overall, one view of synthetic biology can be neatly summarised as "creating in order to understand."

Controlled polymer synthesis--from biomimicry towards synthetic biology.

PubMed

Pasparakis, George; Krasnogor, Natalio; Cronin, Leroy; Davis, Benjamin G; Alexander, Cameron

2010-01-01

The controlled assembly of synthetic polymer structures is now possible with an unprecedented range of functional groups and molecular architectures. In this critical review we consider how the ability to create artificial materials over lengthscales ranging from a few nm to several microns is generating systems that not only begin to mimic those in nature but also may lead to exciting applications in synthetic biology (139 references).

Target of Rapamycin (TOR) in Nutrient Signaling and Growth Control

PubMed Central

Loewith, Robbie; Hall, Michael N.

2011-01-01

TOR (Target Of Rapamycin) is a highly conserved protein kinase that is important in both fundamental and clinical biology. In fundamental biology, TOR is a nutrient-sensitive, central controller of cell growth and aging. In clinical biology, TOR is implicated in many diseases and is the target of the drug rapamycin used in three different therapeutic areas. The yeast Saccharomyces cerevisiae has played a prominent role in both the discovery of TOR and the elucidation of its function. Here we review the TOR signaling network in S. cerevisiae. PMID:22174183

Reprogramming cellular functions with engineered membrane proteins.

PubMed

Arber, Caroline; Young, Melvin; Barth, Patrick

2017-10-01

Taking inspiration from Nature, synthetic biology utilizes and modifies biological components to expand the range of biological functions for engineering new practical devices and therapeutics. While early breakthroughs mainly concerned the design of gene circuits, recent efforts have focused on engineering signaling pathways to reprogram cellular functions. Since signal transduction across cell membranes initiates and controls intracellular signaling, membrane receptors have been targeted by diverse protein engineering approaches despite limited mechanistic understanding of their function. The modular architecture of several receptor families has enabled the empirical construction of chimeric receptors combining domains from distinct native receptors which have found successful immunotherapeutic applications. Meanwhile, progress in membrane protein structure determination, computational modeling and rational design promise to foster the engineering of a broader range of membrane receptor functions. Marrying empirical and rational membrane protein engineering approaches should enable the reprogramming of cells with widely diverse fine-tuned functions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Predator interference effects on biological control: The "paradox" of the generalist predator revisited

NASA Astrophysics Data System (ADS)

Parshad, Rana D.; Bhowmick, Suman; Quansah, Emmanuel; Basheer, Aladeen; Upadhyay, Ranjit Kumar

2016-10-01

An interesting conundrum in biological control questions the efficiency of generalist predators as biological control agents. Theory suggests, generalist predators are poor agents for biological control, primarily due to mutual interference. However field evidence shows they are actually quite effective in regulating pest densities. In this work we provide a plausible answer to this paradox. We analyze a three species model, where a generalist top predator is introduced into an ecosystem as a biological control, to check the population of a middle predator, that in turn is depredating on a prey species. We show that the inclusion of predator interference alone, can cause the solution of the top predator equation to blow-up in finite time, while there is global existence in the no interference case. This result shows that interference could actually cause a population explosion of the top predator, enabling it to control the target species, thus corroborating recent field evidence. Our results might also partially explain the population explosion of certain species, introduced originally for biological control purposes, such as the cane toad (Bufo marinus) in Australia, which now functions as a generalist top predator. We also show both Turing instability and spatio-temporal chaos in the model. Lastly we investigate time delay effects.

Clinical, Functional, and Biological Correlates of Cognitive Dimensions in Major Depressive Disorder – Rationale, Design, and Characteristics of the Cognitive Function and Mood Study (CoFaM-Study)

PubMed Central

Baune, Bernhard T.; Air, Tracy

2016-01-01

Cross-sectional and longitudinal studies exploring clinical, functional, and biological correlates of major depressive disorder are frequent. In this type of research, depression is most commonly defined as a categorical diagnosis based on studies using diagnostic instruments. Given the phenotypic and biological heterogeneity of depression, we chose to focus the phenotypic assessments on three cognitive dimensions of depression including (a) cognitive performance, (b) emotion processing, and (c) social cognitive functioning. Hence, the overall aim of the study is to investigate the long-term clinical course of these cognitive dimensions in depression and its functional (psychosocial) correlates. We also aim to identify biological “genomic” correlates of these three cognitive dimensions of depression. To address the above overall aim, we created the Cognition and Mood Study (CoFaMS) with the key objective to investigate the clinical, functional, and biological correlates of cognitive dimensions of depression by employing a prospective study design and including a healthy control group. The study commenced in April 2015, including patients with a primary diagnosis of a major depressive episode of major depressive disorder or bipolar disorder according to DSM-IV-TR criteria. The assessments cover the three cognitive dimensions of depression (cognitive performance, emotion processing, and social cognition), cognitive function screening instrument, plus functional scales to assess general, work place, and psychosocial function, depression symptom scales, and clinical course of illness. Blood is collected for comprehensive genomic discovery analyses of biological correlates of cognitive dimensions of depression. The CoFaM-Study represents an innovative approach focusing on cognitive dimensions of depression and its functional and biological “genomic” correlates. The CoFaMS team welcomes collaborations with both national and international researchers. PMID:27616997

Clinical, Functional, and Biological Correlates of Cognitive Dimensions in Major Depressive Disorder - Rationale, Design, and Characteristics of the Cognitive Function and Mood Study (CoFaM-Study).

PubMed

Baune, Bernhard T; Air, Tracy

2016-01-01

Cross-sectional and longitudinal studies exploring clinical, functional, and biological correlates of major depressive disorder are frequent. In this type of research, depression is most commonly defined as a categorical diagnosis based on studies using diagnostic instruments. Given the phenotypic and biological heterogeneity of depression, we chose to focus the phenotypic assessments on three cognitive dimensions of depression including (a) cognitive performance, (b) emotion processing, and (c) social cognitive functioning. Hence, the overall aim of the study is to investigate the long-term clinical course of these cognitive dimensions in depression and its functional (psychosocial) correlates. We also aim to identify biological "genomic" correlates of these three cognitive dimensions of depression. To address the above overall aim, we created the Cognition and Mood Study (CoFaMS) with the key objective to investigate the clinical, functional, and biological correlates of cognitive dimensions of depression by employing a prospective study design and including a healthy control group. The study commenced in April 2015, including patients with a primary diagnosis of a major depressive episode of major depressive disorder or bipolar disorder according to DSM-IV-TR criteria. The assessments cover the three cognitive dimensions of depression (cognitive performance, emotion processing, and social cognition), cognitive function screening instrument, plus functional scales to assess general, work place, and psychosocial function, depression symptom scales, and clinical course of illness. Blood is collected for comprehensive genomic discovery analyses of biological correlates of cognitive dimensions of depression. The CoFaM-Study represents an innovative approach focusing on cognitive dimensions of depression and its functional and biological "genomic" correlates. The CoFaMS team welcomes collaborations with both national and international researchers.

Hatch, survival and sensory perception

USDA-ARS?s Scientific Manuscript database

The need to understand the functional biology of nematodes is central both to fundamental science and to practical aspects. Research on the biology of economically important cyst nematodes has frequently had the declared aim of identifying novel control targets based on disruption of the nematode li...

Functional inclusion bodies produced in the yeast Pichia pastoris.

PubMed

Rueda, Fabián; Gasser, Brigitte; Sánchez-Chardi, Alejandro; Roldán, Mònica; Villegas, Sandra; Puxbaum, Verena; Ferrer-Miralles, Neus; Unzueta, Ugutz; Vázquez, Esther; Garcia-Fruitós, Elena; Mattanovich, Diethard; Villaverde, Antonio

2016-10-01

Bacterial inclusion bodies (IBs) are non-toxic protein aggregates commonly produced in recombinant bacteria. They are formed by a mixture of highly stable amyloid-like fibrils and releasable protein species with a significant extent of secondary structure, and are often functional. As nano structured materials, they are gaining biomedical interest because of the combination of submicron size, mechanical stability and biological activity, together with their ability to interact with mammalian cell membranes for subsequent cell penetration in absence of toxicity. Since essentially any protein species can be obtained as IBs, these entities, as well as related protein clusters (e.g., aggresomes), are being explored in biocatalysis and in biomedicine as mechanically stable sources of functional protein. One of the major bottlenecks for uses of IBs in biological interfaces is their potential contamination with endotoxins from producing bacteria. To overcome this hurdle, we have explored here the controlled production of functional IBs in the yeast Pichia pastoris (Komagataella spp.), an endotoxin-free host system for recombinant protein production, and determined the main physicochemical and biological traits of these materials. Quantitative and qualitative approaches clearly indicate the formation of IBs inside yeast, similar in morphology, size and biological activity to those produced in E. coli, that once purified, interact with mammalian cell membranes and penetrate cultured mammalian cells in absence of toxicity. Structurally and functionally similar from those produced in E. coli, the controlled production of IBs in P. pastoris demonstrates that yeasts can be used as convenient platforms for the biological fabrication of self-organizing protein materials in absence of potential endotoxin contamination and with additional advantages regarding, among others, post-translational modifications often required for protein functionality.

Synthetic biology: tools to design microbes for the production of chemicals and fuels.

PubMed

Seo, Sang Woo; Yang, Jina; Min, Byung Eun; Jang, Sungho; Lim, Jae Hyung; Lim, Hyun Gyu; Kim, Seong Cheol; Kim, Se Yeon; Jeong, Jun Hong; Jung, Gyoo Yeol

2013-11-01

The engineering of biological systems to achieve specific purposes requires design tools that function in a predictable and quantitative manner. Recent advances in the field of synthetic biology, particularly in the programmable control of gene expression at multiple levels of regulation, have increased our ability to efficiently design and optimize biological systems to perform designed tasks. Furthermore, implementation of these designs in biological systems highlights the potential of using these tools to build microbial cell factories for the production of chemicals and fuels. In this paper, we review current developments in the design of tools for controlling gene expression at transcriptional, post-transcriptional and post-translational levels, and consider potential applications of these tools. Copyright © 2013 Elsevier Inc. All rights reserved.

Allee effects in tritrophic food chains: some insights in pest biological control.

PubMed

Costa, Michel Iskin da S; Dos Anjos, Lucas

2016-12-01

Release of natural enemies to control pest populations is a common strategy in biological control. However, its effectiveness is supposed to be impaired, among other factors, by Allee effects in the biological control agent and by the fact that introduced pest natural enemies interact with some native species of the ecosystem. In this work, we devise a tritrophic food chain model where the assumptions previously raised are proved correct when a hyperpredator attacks the introduced pest natural enemy by a functional response type 2 or 3. Moreover, success of pest control is shown to be related to the release of large amounts (i.e., inundative releases) of natural enemies. © The authors 2015. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

On-Demand Targeting: Investigating Biology with Proximity-Directed Chemistry

PubMed Central

2016-01-01

Proximity enhancement is a central chemical tenet underpinning an exciting suite of small-molecule toolsets that have allowed us to unravel many biological complexities. The leitmotif of this opus is “tethering”—a strategy in which a multifunctional small molecule serves as a template to bring proteins/biomolecules together. Scaffolding approaches have been powerfully applied to control diverse biological outcomes such as protein–protein association, protein stability, activity, and improve imaging capabilities. A new twist on this strategy has recently appeared, in which the small-molecule probe is engineered to unleash controlled amounts of reactive chemical signals within the microenvironment of a target protein. Modification of a specific target elicits a precisely timed and spatially controlled gain-of-function (or dominant loss-of-function) signaling response. Presented herein is a unique personal outlook conceptualizing the powerful proximity-enhanced chemical biology toolsets into two paradigms: “multifunctional scaffolding” versus “on-demand targeting”. By addressing the latest advances and challenges in the established yet constantly evolving multifunctional scaffolding strategies as well as in the emerging on-demand precision targeting (and related) systems, this Perspective is aimed at choosing when it is best to employ each of the two strategies, with an emphasis toward further promoting novel applications and discoveries stemming from these innovative chemical biology platforms. PMID:26907082

On-Demand Targeting: Investigating Biology with Proximity-Directed Chemistry.

PubMed

Long, Marcus J C; Poganik, Jesse R; Aye, Yimon

2016-03-23

Proximity enhancement is a central chemical tenet underpinning an exciting suite of small-molecule toolsets that have allowed us to unravel many biological complexities. The leitmotif of this opus is "tethering"-a strategy in which a multifunctional small molecule serves as a template to bring proteins/biomolecules together. Scaffolding approaches have been powerfully applied to control diverse biological outcomes such as protein-protein association, protein stability, activity, and improve imaging capabilities. A new twist on this strategy has recently appeared, in which the small-molecule probe is engineered to unleash controlled amounts of reactive chemical signals within the microenvironment of a target protein. Modification of a specific target elicits a precisely timed and spatially controlled gain-of-function (or dominant loss-of-function) signaling response. Presented herein is a unique personal outlook conceptualizing the powerful proximity-enhanced chemical biology toolsets into two paradigms: "multifunctional scaffolding" versus "on-demand targeting". By addressing the latest advances and challenges in the established yet constantly evolving multifunctional scaffolding strategies as well as in the emerging on-demand precision targeting (and related) systems, this Perspective is aimed at choosing when it is best to employ each of the two strategies, with an emphasis toward further promoting novel applications and discoveries stemming from these innovative chemical biology platforms.

Adaptive Neurotechnology for Making Neural Circuits Functional .

NASA Astrophysics Data System (ADS)

Jung, Ranu

2008-03-01

Two of the most important trends in recent technological developments are that technology is increasingly integrated with biological systems and that it is increasingly adaptive in its capabilities. Neuroprosthetic systems that provide lost sensorimotor function after a neural disability offer a platform to investigate this interplay between biological and engineered systems. Adaptive neurotechnology (hardware and software) could be designed to be biomimetic, guided by the physical and programmatic constraints observed in biological systems, and allow for real-time learning, stability, and error correction. An example will present biomimetic neural-network hardware that can be interfaced with the isolated spinal cord of a lower vertebrate to allow phase-locked real-time neural control. Another will present adaptive neural network control algorithms for functional electrical stimulation of the peripheral nervous system to provide desired movements of paralyzed limbs in rodents or people. Ultimately, the frontier lies in being able to utilize the adaptive neurotechnology to promote neuroplasticity in the living system on a long-time scale under co-adaptive conditions.

75 FR 62916 - Re-Delegation by the Under Secretary of State to the Director, Office of Chemical and Biological...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-13

... State to the Director, Office of Chemical and Biological Weapons Affairs, of the Functions and... Secretary of State by the laws of the United States, including by Section 101 of the Chemical Weapons...-delegate to the Director, Office of Chemical and Biological Weapons Affairs, Bureau of Arms Control, [[Page...

Synthetic biology expands chemical control of microorganisms.

PubMed

Ford, Tyler J; Silver, Pamela A

2015-10-01

The tools of synthetic biology allow researchers to change the ways engineered organisms respond to chemical stimuli. Decades of basic biology research and new efforts in computational protein and RNA design have led to the development of small molecule sensors that can be used to alter organism function. These new functions leap beyond the natural propensities of the engineered organisms. They can range from simple fluorescence or growth reporting to pathogen killing, and can involve metabolic coordination among multiple cells or organisms. Herein, we discuss how synthetic biology alters microorganisms' responses to chemical stimuli resulting in the development of microbes as toxicity sensors, disease treatments, and chemical factories. Copyright © 2015 Elsevier Ltd. All rights reserved.

Micro/nanofabricated environments for synthetic biology.

PubMed

Collier, C Patrick; Simpson, Michael L

2011-08-01

A better understanding of how confinement, crowding and reduced dimensionality modulate reactivity and reaction dynamics will aid in the rational and systematic discovery of functionality in complex biological systems. Artificial microfabricated and nanofabricated structures have helped elucidate the effects of nanoscale spatial confinement and segregation on biological behavior, particularly when integrated with microfluidics, through precise control in both space and time of diffusible signals and binding interactions. Examples of nanostructured interfaces for synthetic biology include the development of cell-like compartments for encapsulating biochemical reactions, nanostructured environments for fundamental studies of diffusion, molecular transport and biochemical reaction kinetics, and regulation of biomolecular interactions as functions of microfabricated and nanofabricated topological constraints. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reproductive Biology and Functional Response of Dineulophus phtorimaeae, a Natural Enemy of the Tomato Moth, Tuta absoluta

PubMed Central

Savino, Vivina; Coviella, Carlos E.; Luna, María G.

2012-01-01

The tomato moth, Tuta absoluta (Lepidoptera: Gelechiidae), is a major pest in South America and is at present an important invasive species in the Mediterranean Basin. The larval stadium mines leaves, stems, and fruits, and chemical control is the most used control method in both its original range and the invaded distribution regions. Since current T. absoluta control strategies seem limited, biological control is a prominent tool to be applied abroad. The naturally occurring larval ectoparasitoid in Argentina and Chile Dineulophus phtorimaeae (Hymenoptera: Eulophidae) has been reported to have potential biocontrol efficiency. In this study, the ovigeny strategy of D. phtorimaeae was analyzed throughout the adult female lifetime, and the functional response of females offered a range of 2–15 T. absoluta larvae was measured over a 48-hour period. Mean D. phtorimaeae egg load was 4.15 eggs, and egg production resulted in extremely synovigenic behavior. Meanwhile, a decreasing number of eggs, due to resorption, was found. Proportions of attacked (host-fed and/or parasitized) and only host-fed hosts by the ectoparasitoid were density independent for the tested host range, exhibiting a type I functional response to T. absoluta, with an attack rate of 0.20 host larvae. Meanings of this reproductive strategy in evolutionary time as well as the consequences for augmentative biological control programs are discussed. PMID:23464576

Creating biomaterials with spatially organized functionality.

PubMed

Chow, Lesley W; Fischer, Jacob F

2016-05-01

Biomaterials for tissue engineering provide scaffolds to support cells and guide tissue regeneration. Despite significant advances in biomaterials design and fabrication techniques, engineered tissue constructs remain functionally inferior to native tissues. This is largely due to the inability to recreate the complex and dynamic hierarchical organization of the extracellular matrix components, which is intimately linked to a tissue's biological function. This review discusses current state-of-the-art strategies to control the spatial presentation of physical and biochemical cues within a biomaterial to recapitulate native tissue organization and function. © 2016 by the Society for Experimental Biology and Medicine.

Controlled ecological life support system higher plant flight experiments

NASA Technical Reports Server (NTRS)

Tibbitts, T. W.; Wheeler, R. M.

1984-01-01

Requirements for spaceflight experments which involve higher plants were determined. The plants are studied for use in controlled ecological life support systems (CELSS). Two categories of research requirements are discussed: (1) the physical needs which include nutrient, water and gas exchange requirements; (2) the biological and physiological functions which affect plants in zero gravity environments. Physical problems studies are given the priority since they affect all biological experiments.

Dynamics and Control of a Biomimetic Vehicle Using Biased Wingbeat Forcing Functions: Part 1 - Aerodynamic Model (Postprint)

DTIC Science & Technology

2010-01-01

Experimental Biology, Vol. 46, 1967, pp. 431–443. 5Sane, S. P. and Dickenson , M. H., “The Control of Flight Force by a Flapping Wing: Lift and Drag Force...Production,” The Journal of Experimental Biology, Vol. 204, 2001, pp. 2607–2626. 6Sane, S. P. and Dickenson , M. H., “The aerodynamic effects of wing

Paratransgenesis applied for control of tsetse transmitted sleeping sickness.

PubMed

Aksoy, Serap; Weiss, Brian; Attardo, Geoffrey

2008-01-01

African trypanosomiasis (sleeping sickness) is a major cause of morbidity and mortality in Subsaharan Africa for human and animal health. In the absence of effective vaccines and efficacious drugs, vector control is an alternative intervention tool to break the disease cycle. This chapter describes the vectorial and symbiotic biology of tsetse with emphasis on the current knowledge on tsetse symbiont genomics and functional biology, and tsetse's trypanosome transmission capability. The ability to culture one of tsetse's commensal symbiotic microbes, Sodalis in vitro has allowed for the development of a genetic transformation system for this organism. Tsetse can be repopulated with the modified Sodalis symbiont, which can express foreign gene products (an approach we refer to as paratransgenic expression system). Expanding knowledge on tsetse immunity effectors, on genomics of tsetse symbionts and on tsetse's parasite transmission biology stands to enhance the development and potential application of paratransgenesis as a new vector-control strategy. We describe the hallmarks of the paratransgenic transformation technology where the modified symbionts expressing trypanocidal compounds can be used to manipulate host functions and lead to the control of trypanosomiasis by blocking trypanosome transmission in the tsetse vector.

Mobilizing the rhizosphere microbiome to enhance orchard system resilience

USDA-ARS?s Scientific Manuscript database

Soils possess a wealth of biological resources that can be harnessed for use in the optimization of plant performance in agroecosystems. Functional biological control outcomes, beyond those realized based upon introduction of synthetic microbiomes, have been documented in a variety of instances, an...

Preparation and development of block copolypeptide vesicles and hydrogels for biological and medical applications.

PubMed

Deming, Timothy J

2014-01-01

There have been many recent advances in the controlled polymerization of α-amino acid-N-carboxyanhydride (NCA) monomers into well-defined block copolypeptides. Transition metal initiating systems allow block copolypeptide synthesis with excellent control over number and lengths of block segments, chain length distribution, and chain-end functionality. Using this and other methods, block copolypeptides of controlled dimensions have been prepared and their self-assembly into organized structures studied by many research groups. The ability of well-defined block copolypeptides to assemble into supramolecular copolypeptide vesicles and hydrogels has led to the development of these materials for use in biological and medical applications. These assemblies have been found to possess unique properties that are derived from the amino acid building blocks and ordered conformations of the polypeptide segments. Recent work on the incorporation of active and stimulus-responsive functionality in these materials has tremendously increased their potential for use in biological and medical studies. © 2014 Wiley Periodicals, Inc.

Fabrication of enzyme-degradable and size-controlled protein nanowires using single particle nano-fabrication technique

PubMed Central

Omichi, Masaaki; Asano, Atsushi; Tsukuda, Satoshi; Takano, Katsuyoshi; Sugimoto, Masaki; Saeki, Akinori; Sakamaki, Daisuke; Onoda, Akira; Hayashi, Takashi; Seki, Shu

2014-01-01

Protein nanowires exhibiting specific biological activities hold promise for interacting with living cells and controlling and predicting biological responses such as apoptosis, endocytosis and cell adhesion. Here we report the result of the interaction of a single high-energy charged particle with protein molecules, giving size-controlled protein nanowires with an ultra-high aspect ratio of over 1,000. Degradation of the human serum albumin nanowires was examined using trypsin. The biotinylated human serum albumin nanowires bound avidin, demonstrating the high affinity of the nanowires. Human serum albumin–avidin hybrid nanowires were also fabricated from a solid state mixture and exhibited good mechanical strength in phosphate-buffered saline. The biotinylated human serum albumin nanowires can be transformed into nanowires exhibiting a biological function such as avidin–biotinyl interactions and peroxidase activity. The present technique is a versatile platform for functionalizing the surface of any protein molecule with an extremely large surface area. PMID:24770668

Bioinspired microrobots

NASA Astrophysics Data System (ADS)

Palagi, Stefano; Fischer, Peer

2018-06-01

Microorganisms can move in complex media, respond to the environment and self-organize. The field of microrobotics strives to achieve these functions in mobile robotic systems of sub-millimetre size. However, miniaturization of traditional robots and their control systems to the microscale is not a viable approach. A promising alternative strategy in developing microrobots is to implement sensing, actuation and control directly in the materials, thereby mimicking biological matter. In this Review, we discuss design principles and materials for the implementation of robotic functionalities in microrobots. We examine different biological locomotion strategies, and we discuss how they can be artificially recreated in magnetic microrobots and how soft materials improve control and performance. We show that smart, stimuli-responsive materials can act as on-board sensors and actuators and that `active matter' enables autonomous motion, navigation and collective behaviours. Finally, we provide a critical outlook for the field of microrobotics and highlight the challenges that need to be overcome to realize sophisticated microrobots, which one day might rival biological machines.

Protein-protein recognition control by modulating electrostatic interactions.

PubMed

Han, Song; Yin, Shijin; Yi, Hong; Mouhat, Stéphanie; Qiu, Su; Cao, Zhijian; Sabatier, Jean-Marc; Wu, Yingliang; Li, Wenxin

2010-06-04

Protein-protein control recognition remains a huge challenge, and its development depends on understanding the chemical and biological mechanisms by which these interactions occur. Here we describe a protein-protein control recognition technique based on the dominant electrostatic interactions occurring between the proteins. We designed a potassium channel inhibitor, BmP05-T, that was 90.32% identical to wild-type BmP05. Negatively charged residues were translocated from the nonbinding interface to the binding interface of BmP05 inhibitor, such that BmP05-T now used BmP05 nonbinding interface as the binding interface. This switch demonstrated that nonbinding interfaces were able to control the orientation of protein binding interfaces in the process of protein-protein recognition. The novel function findings of BmP05-T peptide suggested that the control recognition technique described here had the potential for use in designing and utilizing functional proteins in many biological scenarios.

Long Noncoding RNAs: a New Regulatory Code in Metabolic Control

PubMed Central

Zhao, Xu-Yun; Lin, Jiandie D.

2015-01-01

Long noncoding RNAs (lncRNAs) are emerging as an integral part of the regulatory information encoded in the genome. LncRNAs possess the unique capability to interact with nucleic acids and proteins and exert discrete effects on numerous biological processes. Recent studies have delineated multiple lncRNA pathways that control metabolic tissue development and function. The expansion of the regulatory code that links nutrient and hormonal signals to tissue metabolism gives new insights into the genetic and pathogenic mechanisms underlying metabolic disease. This review discusses lncRNA biology with a focus on its role in the development, signaling, and function of key metabolic tissues. PMID:26410599

A biomimetic functionalization approach to integration of carbon nanoutbes into biological systems

NASA Astrophysics Data System (ADS)

Chen, Xing; Tam, Un Chong; Bertozzi, Carolyn; Zettl, Alex

2006-03-01

Due to their remarkable structural, electrical, and mechanical properties, carbon nanotubes (CNTs) have potential applications in biology ranging from imaging and tissue engineering. To realize these applications, however, new strategies for controlling the interaction between CNTs and biological systems such as proteins and cells are required. Here we describe a biomimetic approach to functionalize CNTs and therefore render them biocompatibility in order to facilitate their integration into biological systems. CNTs were coated with synthetic gycopolymers that mimic cell surface mucin gycoproteins. The functionalized CNTs were soluble in water, resisted non-specific protein binding and bound specifically to biomolecules. The coated CNTs could then be integrated onto mammalian cell surface by virtue of glycan-receptor interactions. Furthermore, the functionalized CNTs are non-toxic to cells. This strategy offers new opportunities for development of biosensor to probe biological processes. References: 1. X. Chen, G. S. Lee, A. Zettl, C. R. Bertozzi, Angewandte Chemie-International Edition 43, 6111 (2004). 2. X. Chen, U. C. Tam, J. L. Czlapanski, G. S. Lee, D. Rabuka, A. Zettl, C. R. Bertozzi, submitted.

Copper metallothioneins.

PubMed

Calvo, Jenifer; Jung, Hunmin; Meloni, Gabriele

2017-04-01

Metallothioneins (MTs) are a class of low molecular weight and cysteine-rich metal binding proteins present in all the branches of the tree of life. MTs efficiently bind with high affinity several essential and toxic divalent and monovalent transition metals by forming characteristic polynuclear metal-thiolate clusters within their structure. MTs fulfil multiple biological functions related to their metal binding properties, with essential roles in both Zn(II) and Cu(I) homeostasis as well as metal detoxification. Depending on the organism considered, the primary sequence, and the specific physiological and metabolic status, Cu(I)-bound MT isoforms have been isolated, and their chemistry and biology characterized. Besides the recognized role in the biochemistry of divalent metals, it is becoming evident that unique biological functions in selectively controlling copper levels, its reactivity as well as copper-mediated biochemical processes have evolved in some members of the MT superfamily. Selected examples are reviewed to highlight the peculiar chemical properties and biological functions of copper MTs. © 2016 IUBMB Life, 69(4):236-245, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Essential roles of Gab1 tyrosine phosphorylation in growth factor-mediated signaling and angiogenesis.

PubMed

Wang, Weiye; Xu, Suowen; Yin, Meimei; Jin, Zheng Gen

2015-02-15

Growth factors and their downstream receptor tyrosine kinases (RTKs) mediate a number of biological processes controlling cell function. Adaptor (docking) proteins, which consist exclusively of domains and motifs that mediate molecular interactions, link receptor activation to downstream effectors. Recent studies have revealed that Grb2-associated-binders (Gab) family members (including Gab1, Gab2, and Gab3), when phosphorylated on tyrosine residues, provide binding sites for multiple effector proteins, such as Src homology-2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) and phosphatidylinositol 3-kinase (PI3K) regulatory subunit p85, thereby playing important roles in transducing RTKs-mediated signals into pathways with diversified biological functions. Here, we provide an up-to-date overview on the domain structure and biological functions of Gab1, the most intensively studied Gab family protein, in growth factor signaling and biological functions, with a special focus on angiogenesis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The Biology of REM Sleep

PubMed Central

Peever, John; Fuller, Patrick M.

2018-01-01

Considerable advances in our understanding of the mechanisms and functions of rapid-eye-movement (REM) sleep have occurred over the past decade. Much of this progress can be attributed to the development of new neuroscience tools that have enabled high-precision interrogation of brain circuitry linked with REM sleep control, in turn revealing how REM sleep mechanisms themselves impact processes such as sensorimotor function. This review is intended to update the general scientific community about the recent mechanistic, functional and conceptual developments in our current understanding of REM sleep biology and pathobiology. Specifically, this review outlines the historical origins of the discovery of REM sleep, the diversity of REM sleep expression across and within species, the potential functions of REM sleep (e.g., memory consolidation), the neural circuits that control REM sleep, and how dysfunction of REM sleep mechanisms underlie debilitating sleep disorders such as REM sleep behaviour disorder and narcolepsy. PMID:26766231

Molecular biomimetics: utilizing nature's molecular ways in practical engineering.

PubMed

Tamerler, Candan; Sarikaya, Mehmet

2007-05-01

In nature, proteins are the machinery that accomplish many functions through their specific recognition and interactions in biological systems from single-celled to multicellular organisms. Biomolecule-material interaction is accomplished via molecular specificity, leading to the formation of controlled structures and functions at all scales of dimensional hierarchy. Through evolution, molecular recognition and, consequently, functions developed through successive cycles of mutation and selection. Using biology as a guide, we can now understand, engineer and control peptide-material interactions and exploit these to tailor novel materials and systems for practical applications. We adapted combinatorial biology protocols to display peptide libraries, either on the cell surface or on phages, to select short peptides specific to a variety of practical materials systems. Following the selection step, we determined the kinetics and stability of peptide binding experimentally to understand the bound peptide structure via modeling and its assembly via atomic force microscopy. The peptides were further engineered to have multiple repeats or their amino acid sequences varied to tailor their function. Both nanoparticles and flat inorganic substrates containing multimaterials patterned at the nano- and microscales were used for self-directed immobilization of molecular constructs. The molecular biomimetic approach opens up new avenues for the design and utilization of multifunctional molecular systems with wide ranging applications, from tissue engineering, drug delivery and biosensors, to nanotechnology and bioremediation. Here we give examples of protein-mediated functional materials in biology, peptide selection and engineering with affinity to inorganics, demonstrate potential utilizations in materials science, engineering and medicine, and describe future prospects.

Dissipative structures and biological rhythms

NASA Astrophysics Data System (ADS)

Goldbeter, Albert

2017-10-01

Sustained oscillations abound in biological systems. They occur at all levels of biological organization over a wide range of periods, from a fraction of a second to years, and with a variety of underlying mechanisms. They control major physiological functions, and their dysfunction is associated with a variety of physiological disorders. The goal of this review is (i) to give an overview of the main rhythms observed at the cellular and supracellular levels, (ii) to briefly describe how the study of biological rhythms unfolded in the course of time, in parallel with studies on chemical oscillations, (iii) to present the major roles of biological rhythms in the control of physiological functions, and (iv) the pathologies associated with the alteration, disappearance, or spurious occurrence of biological rhythms. Two tables present the main examples of cellular and supracellular rhythms ordered according to their period, and their role in physiology and pathophysiology. Among the rhythms discussed are neural and cardiac rhythms, metabolic oscillations such as those occurring in glycolysis in yeast, intracellular Ca++ oscillations, cyclic AMP oscillations in Dictyostelium amoebae, the segmentation clock that controls somitogenesis, pulsatile hormone secretion, circadian rhythms which occur in all eukaryotes and some bacteria with a period close to 24 h, the oscillatory dynamics of the enzymatic network driving the cell cycle, and oscillations in transcription factors such as NF-ΚB and tumor suppressors such as p53. Ilya Prigogine's concept of dissipative structures applies to temporal oscillations and allows us to unify within a common framework the various rhythms observed at different levels of biological organization, regardless of their period and underlying mechanism.

Growth control of the eukaryote cell: a systems biology study in yeast.

PubMed

Castrillo, Juan I; Zeef, Leo A; Hoyle, David C; Zhang, Nianshu; Hayes, Andrew; Gardner, David Cj; Cornell, Michael J; Petty, June; Hakes, Luke; Wardleworth, Leanne; Rash, Bharat; Brown, Marie; Dunn, Warwick B; Broadhurst, David; O'Donoghue, Kerry; Hester, Svenja S; Dunkley, Tom Pj; Hart, Sarah R; Swainston, Neil; Li, Peter; Gaskell, Simon J; Paton, Norman W; Lilley, Kathryn S; Kell, Douglas B; Oliver, Stephen G

2007-01-01

Cell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive studies at the transcriptional, proteomic and metabolic levels under defined controlled conditions are currently lacking. Metabolic control analysis is being exploited in a systems biology study of the eukaryotic cell. Using chemostat culture, we have measured the impact of changes in flux (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear growth-rate-associated trends and discriminates between carbon-sufficient and carbon-limited conditions. Genes consistently and significantly upregulated with increasing growth rate are frequently essential and encode evolutionarily conserved proteins of known function that participate in many protein-protein interactions. In contrast, more unknown, and fewer essential, genes are downregulated with increasing growth rate; their protein products rarely interact with one another. A large proportion of yeast genes under positive growth-rate control share orthologs with other eukaryotes, including humans. Significantly, transcription of genes encoding components of the TOR complex (a major controller of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover, integrative studies reveal the extent and importance of post-transcriptional control, patterns of control of metabolic fluxes at the level of enzyme synthesis, and the relevance of specific enzymatic reactions in the control of metabolic fluxes during cell growth. This work constitutes a first comprehensive systems biology study on growth-rate control in the eukaryotic cell. The results have direct implications for advanced studies on cell growth, in vivo regulation of metabolic fluxes for comprehensive metabolic engineering, and for the design of genome-scale systems biology models of the eukaryotic cell.

Growth control of the eukaryote cell: a systems biology study in yeast

PubMed Central

Castrillo, Juan I; Zeef, Leo A; Hoyle, David C; Zhang, Nianshu; Hayes, Andrew; Gardner, David CJ; Cornell, Michael J; Petty, June; Hakes, Luke; Wardleworth, Leanne; Rash, Bharat; Brown, Marie; Dunn, Warwick B; Broadhurst, David; O'Donoghue, Kerry; Hester, Svenja S; Dunkley, Tom PJ; Hart, Sarah R; Swainston, Neil; Li, Peter; Gaskell, Simon J; Paton, Norman W; Lilley, Kathryn S; Kell, Douglas B; Oliver, Stephen G

2007-01-01

Background Cell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive studies at the transcriptional, proteomic and metabolic levels under defined controlled conditions are currently lacking. Results Metabolic control analysis is being exploited in a systems biology study of the eukaryotic cell. Using chemostat culture, we have measured the impact of changes in flux (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear growth-rate-associated trends and discriminates between carbon-sufficient and carbon-limited conditions. Genes consistently and significantly upregulated with increasing growth rate are frequently essential and encode evolutionarily conserved proteins of known function that participate in many protein-protein interactions. In contrast, more unknown, and fewer essential, genes are downregulated with increasing growth rate; their protein products rarely interact with one another. A large proportion of yeast genes under positive growth-rate control share orthologs with other eukaryotes, including humans. Significantly, transcription of genes encoding components of the TOR complex (a major controller of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover, integrative studies reveal the extent and importance of post-transcriptional control, patterns of control of metabolic fluxes at the level of enzyme synthesis, and the relevance of specific enzymatic reactions in the control of metabolic fluxes during cell growth. Conclusion This work constitutes a first comprehensive systems biology study on growth-rate control in the eukaryotic cell. The results have direct implications for advanced studies on cell growth, in vivo regulation of metabolic fluxes for comprehensive metabolic engineering, and for the design of genome-scale systems biology models of the eukaryotic cell. PMID:17439666

Effects of biocontrol on short-term nutrient dynamics in a tamarix-invaded riparian ecosystem

USDA-ARS?s Scientific Manuscript database

Background/Question/Methods Saltcedar (Tamarix ramosissima) invasion and subsequent dominance in biologically and functionally diverse riparian ecosystems across the western U.S. has lead to release of the leaf beetle (Diorhabda elongata) as a biological control agent, and has resulted in large-sca...

The Functions of Metamorphic Metallothioneins in Zinc and Copper Metabolism.

PubMed

Krężel, Artur; Maret, Wolfgang

2017-06-09

Recent discoveries in zinc biology provide a new platform for discussing the primary physiological functions of mammalian metallothioneins (MTs) and their exquisite zinc-dependent regulation. It is now understood that the control of cellular zinc homeostasis includes buffering of Zn 2+ ions at picomolar concentrations, extensive subcellular re-distribution of Zn 2+ , the loading of exocytotic vesicles with zinc species, and the control of Zn 2+ ion signalling. In parallel, characteristic features of human MTs became known: their graded affinities for Zn 2+ and the redox activity of their thiolate coordination environments. Unlike the single species that structural models of mammalian MTs describe with a set of seven divalent or eight to twelve monovalent metal ions, MTs are metamorphic. In vivo, they exist as many species differing in redox state and load with different metal ions. The functions of mammalian MTs should no longer be considered elusive or enigmatic because it is now evident that the reactivity and coordination dynamics of MTs with Zn 2+ and Cu⁺ match the biological requirements for controlling-binding and delivering-these cellular metal ions, thus completing a 60-year search for their functions. MT represents a unique biological principle for buffering the most competitive essential metal ions Zn 2+ and Cu⁺. How this knowledge translates to the function of other families of MTs awaits further insights into the specifics of how their properties relate to zinc and copper metabolism in other organisms.

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.

Pathway analysis from lists of microRNAs: common pitfalls and alternative strategy

PubMed Central

Godard, Patrice; van Eyll, Jonathan

2015-01-01

MicroRNAs (miRNAs) are involved in the regulation of gene expression at a post-transcriptional level. As such, monitoring miRNA expression has been increasingly used to assess their role in regulatory mechanisms of biological processes. In large scale studies, once miRNAs of interest have been identified, the target genes they regulate are often inferred using algorithms or databases. A pathway analysis is then often performed in order to generate hypotheses about the relevant biological functions controlled by the miRNA signature. Here we show that the method widely used in scientific literature to identify these pathways is biased and leads to inaccurate results. In addition to describing the bias and its origin we present an alternative strategy to identify potential biological functions specifically impacted by a miRNA signature. More generally, our study exemplifies the crucial need of relevant negative controls when developing, and using, bioinformatics methods. PMID:25800743

Molecular biomimetics: nanotechnology through biology.

PubMed

Sarikaya, Mehmet; Tamerler, Candan; Jen, Alex K-Y; Schulten, Klaus; Baneyx, François

2003-09-01

Proteins, through their unique and specific interactions with other macromolecules and inorganics, control structures and functions of all biological hard and soft tissues in organisms. Molecular biomimetics is an emerging field in which hybrid technologies are developed by using the tools of molecular biology and nanotechnology. Taking lessons from biology, polypeptides can now be genetically engineered to specifically bind to selected inorganic compounds for applications in nano- and biotechnology. This review discusses combinatorial biological protocols, that is, bacterial cell surface and phage-display technologies, in the selection of short sequences that have affinity to (noble) metals, semiconducting oxides and other technological compounds. These genetically engineered proteins for inorganics (GEPIs) can be used in the assembly of functional nanostructures. Based on the three fundamental principles of molecular recognition, self-assembly and DNA manipulation, we highlight successful uses of GEPI in nanotechnology.

Enhancing biological relevance of a weighted gene co-expression network for functional module identification.

PubMed

Prom-On, Santitham; Chanthaphan, Atthawut; Chan, Jonathan Hoyin; Meechai, Asawin

2011-02-01

Relationships among gene expression levels may be associated with the mechanisms of the disease. While identifying a direct association such as a difference in expression levels between case and control groups links genes to disease mechanisms, uncovering an indirect association in the form of a network structure may help reveal the underlying functional module associated with the disease under scrutiny. This paper presents a method to improve the biological relevance in functional module identification from the gene expression microarray data by enhancing the structure of a weighted gene co-expression network using minimum spanning tree. The enhanced network, which is called a backbone network, contains only the essential structural information to represent the gene co-expression network. The entire backbone network is decoupled into a number of coherent sub-networks, and then the functional modules are reconstructed from these sub-networks to ensure minimum redundancy. The method was tested with a simulated gene expression dataset and case-control expression datasets of autism spectrum disorder and colorectal cancer studies. The results indicate that the proposed method can accurately identify clusters in the simulated dataset, and the functional modules of the backbone network are more biologically relevant than those obtained from the original approach.

Thiol/disulfide redox states in signaling and sensing

PubMed Central

Go, Young-Mi; Jones, Dean P.

2015-01-01

Rapid advances in redox systems biology are creating new opportunities to understand complexities of human disease and contributions of environmental exposures. New understanding of thiol-disulfide systems have occurred during the past decade as a consequence of the discoveries that thiol and disulfide systems are maintained in kinetically controlled steady-states displaced from thermodynamic equilibrium, that a widely distributed family of NADPH oxidases produces oxidants that function in cell signaling, and that a family of peroxiredoxins utilize thioredoxin as a reductant to complement the well-studied glutathione antioxidant system for peroxide elimination and redox regulation. This review focuses on thiol/disulfide redox state in biologic systems and the knowledge base available to support development of integrated redox systems biology models to better understand the function and dysfunction of thiol-disulfide redox systems. In particular, central principles have emerged concerning redox compartmentalization and utility of thiol/disulfide redox measures as indicators of physiologic function. Advances in redox proteomics show that, in addition to functioning in protein active sites and cell signaling, cysteine residues also serve as redox sensors to integrate biologic functions. These advances provide a framework for translation of redox systems biology concepts to practical use in understanding and treating human disease. Biological responses to cadmium, a widespread environmental agent, are used to illustrate the utility of these advances to the understanding of complex pleiotropic toxicities. PMID:23356510

The semiotics of control and modeling relations in complex systems.

PubMed

Joslyn, C

2001-01-01

We provide a conceptual analysis of ideas and principles from the systems theory discourse which underlie Pattee's semantic or semiotic closure, which is itself foundational for a school of theoretical biology derived from systems theory and cybernetics, and is now being related to biological semiotics and explicated in the relational biological school of Rashevsky and Rosen. Atomic control systems and models are described as the canonical forms of semiotic organization, sharing measurement relations, but differing topologically in that control systems are circularly and models linearly related to their environments. Computation in control systems is introduced, motivating hierarchical decomposition, hybrid modeling and control systems, and anticipatory or model-based control. The semiotic relations in complex control systems are described in terms of relational constraints, and rules and laws are distinguished as contingent and necessary functional entailments, respectively. Finally, selection as a meta-level of constraint is introduced as the necessary condition for semantic relations in control systems and models.

Hierarchical Feedback Modules and Reaction Hubs in Cell Signaling Networks

PubMed Central

Xu, Jianfeng; Lan, Yueheng

2015-01-01

Despite much effort, identification of modular structures and study of their organizing and functional roles remain a formidable challenge in molecular systems biology, which, however, is essential in reaching a systematic understanding of large-scale cell regulation networks and hence gaining capacity of exerting effective interference to cell activity. Combining graph theoretic methods with available dynamics information, we successfully retrieved multiple feedback modules of three important signaling networks. These feedbacks are structurally arranged in a hierarchical way and dynamically produce layered temporal profiles of output signals. We found that global and local feedbacks act in very different ways and on distinct features of the information flow conveyed by signal transduction but work highly coordinately to implement specific biological functions. The redundancy embodied with multiple signal-relaying channels and feedback controls bestow great robustness and the reaction hubs seated at junctions of different paths announce their paramount importance through exquisite parameter management. The current investigation reveals intriguing general features of the organization of cell signaling networks and their relevance to biological function, which may find interesting applications in analysis, design and control of bio-networks. PMID:25951347

Bio-hybrid cell-based actuators for microsystems.

PubMed

Carlsen, Rika Wright; Sitti, Metin

2014-10-15

As we move towards the miniaturization of devices to perform tasks at the nano and microscale, it has become increasingly important to develop new methods for actuation, sensing, and control. Over the past decade, bio-hybrid methods have been investigated as a promising new approach to overcome the challenges of scaling down robotic and other functional devices. These methods integrate biological cells with artificial components and therefore, can take advantage of the intrinsic actuation and sensing functionalities of biological cells. Here, the recent advancements in bio-hybrid actuation are reviewed, and the challenges associated with the design, fabrication, and control of bio-hybrid microsystems are discussed. As a case study, focus is put on the development of bacteria-driven microswimmers, which has been investigated as a targeted drug delivery carrier. Finally, a future outlook for the development of these systems is provided. The continued integration of biological and artificial components is envisioned to enable the performance of tasks at a smaller and smaller scale in the future, leading to the parallel and distributed operation of functional systems at the microscale. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cardiac Muscle-cell Based Actuator and Self-stabilizing Biorobot - PART 1.

PubMed

Holley, Merrel T; Nagarajan, Neerajha; Danielson, Christian; Zorlutuna, Pinar; Park, Kidong

2017-07-11

Biological machines often referred to as biorobots, are living cell- or tissue-based devices that are powered solely by the contractile activity of living components. Due to their inherent advantages, biorobots are gaining interest as alternatives to traditional fully artificial robots. Various studies have focused on harnessing the power of biological actuators, but only recently studies have quantitatively characterized the performance of biorobots and studied their geometry to enhance functionality and efficiency. Here, we demonstrate the development of a self-stabilizing swimming biorobot that can maintain its pitch, depth, and roll without external intervention. The design and fabrication of the PDMS scaffold for the biological actuator and biorobot followed by the functionalization with fibronectin is described in this first part. In the second part of this two-part article, we detail the incorporation of cardiomyocytes and characterize the biological actuator and biorobot function. Both incorporate a base and tail (cantilever) which produce fin-based propulsion. The tail is constructed with soft lithography techniques using PDMS and laser engraving. After incorporating the tail with the device base, it is functionalized with a cell adhesive protein and seeded confluently with cardiomyocytes. The base of the biological actuator consists of a solid PDMS block with a central glass bead (acts as a weight). The base of the biorobot consists of two composite PDMS materials, Ni-PDMS and microballoon-PDMS (MB-PDMS). The nickel powder (in Ni-PDMS) allows magnetic control of the biorobot during cells seeding and stability during locomotion. Microballoons (in MB-PDMS) decrease the density of MB-PDMS, and enable the biorobot to float and swim steadily. The use of these two materials with different mass densities, enabled precise control over the weight distribution to ensure a positive restoration force at any angle of the biorobot. This technique produces a magnetically controlled self-stabilizing swimming biorobot.

3D-printed gelatin scaffolds of differing pore geometry modulate hepatocyte function and gene expression.

PubMed

Lewis, Phillip L; Green, Richard M; Shah, Ramille N

2018-03-15

Three dimensional (3D) printing is highly amenable to the fabrication of tissue-engineered organs of a repetitive microstructure such as the liver. The creation of uniform and geometrically repetitive tissue scaffolds can also allow for the control over cellular aggregation and nutrient diffusion. However, the effect of differing geometries, while controlling for pore size, has yet to be investigated in the context of hepatocyte function. In this study, we show the ability to precisely control pore geometry of 3D-printed gelatin scaffolds. An undifferentiated hepatocyte cell line (HUH7) demonstrated high viability and proliferation when seeded on 3D-printed scaffolds of two different geometries. However, hepatocyte specific functions (albumin secretion, CYP activity, and bile transport) increases in more interconnected 3D-printed gelatin cultures compared to a less interconnected geometry and to 2D controls. Additionally, we also illustrate the disparity between gene expression and protein function in simple 2D culture modes, and that recreation of a physiologically mimetic 3D environment is necessary to induce both expression and function of cultured hepatocytes. Three dimensional (3D) printing provides tissue engineers the ability spatially pattern cells and materials in precise geometries, however the biological effects of scaffold geometry on soft tissues such as the liver have not been rigorously investigated. In this manuscript, we describe a method to 3D print gelatin into well-defined repetitive geometries that show clear differences in biological effects on seeded hepatocytes. We show that a relatively simple and widely used biomaterial, such as gelatin, can significantly modulate biological processes when fabricated into specific 3D geometries. Furthermore, this study expands upon past research into hepatocyte aggregation by demonstrating how it can be manipulated to enhance protein function, and how function and expression may not precisely correlate in 2D models. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Integrated omics for the identification of key functionalities in biological wastewater treatment microbial communities.

PubMed

Narayanasamy, Shaman; Muller, Emilie E L; Sheik, Abdul R; Wilmes, Paul

2015-05-01

Biological wastewater treatment plants harbour diverse and complex microbial communities which prominently serve as models for microbial ecology and mixed culture biotechnological processes. Integrated omic analyses (combined metagenomics, metatranscriptomics, metaproteomics and metabolomics) are currently gaining momentum towards providing enhanced understanding of community structure, function and dynamics in situ as well as offering the potential to discover novel biological functionalities within the framework of Eco-Systems Biology. The integration of information from genome to metabolome allows the establishment of associations between genetic potential and final phenotype, a feature not realizable by only considering single 'omes'. Therefore, in our opinion, integrated omics will become the future standard for large-scale characterization of microbial consortia including those underpinning biological wastewater treatment processes. Systematically obtained time and space-resolved omic datasets will allow deconvolution of structure-function relationships by identifying key members and functions. Such knowledge will form the foundation for discovering novel genes on a much larger scale compared with previous efforts. In general, these insights will allow us to optimize microbial biotechnological processes either through better control of mixed culture processes or by use of more efficient enzymes in bioengineering applications. © 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Leveraging advances in biology to design biomaterials

NASA Astrophysics Data System (ADS)

Darnell, Max; Mooney, David J.

2017-12-01

Biomaterials have dramatically increased in functionality and complexity, allowing unprecedented control over the cells that interact with them. From these engineering advances arises the prospect of improved biomaterial-based therapies, yet practical constraints favour simplicity. Tools from the biology community are enabling high-resolution and high-throughput bioassays that, if incorporated into a biomaterial design framework, could help achieve unprecedented functionality while minimizing the complexity of designs by identifying the most important material parameters and biological outputs. However, to avoid data explosions and to effectively match the information content of an assay with the goal of the experiment, material screens and bioassays must be arranged in specific ways. By borrowing methods to design experiments and workflows from the bioprocess engineering community, we outline a framework for the incorporation of next-generation bioassays into biomaterials design to effectively optimize function while minimizing complexity. This framework can inspire biomaterials designs that maximize functionality and translatability.

Differential effects of plant species on a mite pest (Tetranychus utricae) and its predator (Phytoseiulus persimilis): implications for biological control.

PubMed

Skirvin, D J; de Courcy Williams, M

1999-06-01

The influence of plant species on the population dynamics of the spider mite pest, Tetranychus urticae, and its predator, Phytoseiulus persimilis, was examined as a prerequisite to effective biological control on ornamental nursery stock. Experiments have been done to investigate how the development, fecundity and movement of T. urticae, and the movement of P. persimilis were affected by plant species. A novel experimental method, which incorporates plant structure, was used to investigate the functional response of P. persimilis. Development times for T. urticae were consistent with published data and did not differ with plant species in a biologically meaningful way. Plant species was shown to have a major influence on fecundity (P < 0.001) and movement of the pest mite (P < 0.01), but no influence on the movement of the predator. The movement of both pest and predator was shown to be related to the density of the adult pest mites on the plant (P < 0.001). Plant structure affected the functional response, particularly in relation to the ability of the predator to locate prey at low densities. The impact of these findings on the effective use of biological control on ornamental nursery stock is discussed.

Synergizing Engineering and Biology to Treat and Model Skeletal Muscle Injury and Disease

PubMed Central

Bursac, Nenad; Juhas, Mark; Rando, Thomas A.

2016-01-01

Although skeletal muscle is one of the most regenerative organs in our body, various genetic defects, alterations in extrinsic signaling, or substantial tissue damage can impair muscle function and the capacity for self-repair. The diversity and complexity of muscle disorders have attracted much interest from both cell biologists and, more recently, bioengineers, leading to concentrated efforts to better understand muscle pathology and develop more efficient therapies. This review describes the biological underpinnings of muscle development, repair, and disease, and discusses recent bioengineering efforts to design and control myomimetic environments, both to study muscle biology and function and to aid in the development of new drug, cell, and gene therapies for muscle disorders. The synergy between engineering-aided biological discovery and biology-inspired engineering solutions will be the path forward for translating laboratory results into clinical practice. PMID:26643021

A Combination of Hand-Held Models and Computer Imaging Programs Helps Students Answer Oral Questions about Molecular Structure and Function: A Controlled Investigation of Student Learning

ERIC Educational Resources Information Center

Harris, Michelle A.; Peck, Ronald F.; Colton, Shannon; Morris, Jennifer; Neto, Elias Chaibub; Kallio, Julie

2009-01-01

We conducted a controlled investigation to examine whether a combination of computer imagery and tactile tools helps introductory cell biology laboratory undergraduate students better learn about protein structure/function relationships as compared with computer imagery alone. In all five laboratory sections, students used the molecular imaging…

Towards Self-Assembled Hybrid Artificial Cells: Novel Bottom-Up Approaches to Functional Synthetic Membranes

PubMed Central

Brea, Roberto J.; Hardy, Michael D.; Devaraj, Neal K.

2015-01-01

There has been increasing interest in utilizing bottom-up approaches to develop synthetic cells. A popular methodology is the integration of functionalized synthetic membranes with biological systems, producing “hybrid” artificial cells. This Concept article covers recent advances and the current state-of-the-art of such hybrid systems. Specifically, we describe minimal supramolecular constructs that faithfully mimic the structure and/or function of living cells, often by controlling the assembly of highly ordered membrane architectures with defined functionality. These studies give us a deeper understanding of the nature of living systems, bring new insights into the origin of cellular life, and provide novel synthetic chassis for advancing synthetic biology. PMID:26149747

Venom Proteins from Parasitoid Wasps and Their Biological Functions

PubMed Central

Moreau, Sébastien J. M.; Asgari, Sassan

2015-01-01

Parasitoid wasps are valuable biological control agents that suppress their host populations. Factors introduced by the female wasp at parasitization play significant roles in facilitating successful development of the parasitoid larva either inside (endoparasitoid) or outside (ectoparasitoid) the host. Wasp venoms consist of a complex cocktail of proteinacious and non-proteinacious components that may offer agrichemicals as well as pharmaceutical components to improve pest management or health related disorders. Undesirably, the constituents of only a small number of wasp venoms are known. In this article, we review the latest research on venom from parasitoid wasps with an emphasis on their biological function, applications and new approaches used in venom studies. PMID:26131769

Microvalve controlled multi-functional microfluidic chip for divisional cell co-culture.

PubMed

Li, Rui; Zhang, Xingjian; Lv, Xuefei; Geng, Lina; Li, Yongrui; Qin, Kuiwei; Deng, Yulin

2017-12-15

Pneumatic micro-valve controlled microfluidic chip provides precise fluidic control for cell manipulation. In this paper, a multi-functional microfluidic chip was designed for three separate experiments: 1. Different cell lines were dispensed and cultured; 2. Three transfected SH-SY5Y cells were introduced and treated with methyl-phenyl-pyridinium (MPP + ) as drug delivery mode; 3. Specific protection and interaction were observed among cell co-culture after nerve damage. The outcomes revealed the potential and practicability of our entire multi-functional pneumatic chip system on different cell biology applications. Copyright © 2017. Published by Elsevier Inc.

Biological hydrogels as selective diffusion barriers.

PubMed

Lieleg, Oliver; Ribbeck, Katharina

2011-09-01

The controlled exchange of molecules between organelles, cells, or organisms and their environment is crucial for life. Biological gels such as mucus, the extracellular matrix (ECM), and the biopolymer barrier within the nuclear pore are well suited to achieve such a selective exchange, allowing passage of particular molecules while rejecting many others. Although hydrogel-based filters are integral parts of biology, clear concepts of how their barrier function is controlled at a microscopic level are still missing. We summarize here our current understanding of how selective filtering is established by different biopolymer-based hydrogels. We ask if the modulation of microscopic particle transport in biological hydrogels is based on a generic filtering principle which employs biochemical/biophysical interactions with the filtered molecules rather than size-exclusion effects. Copyright © 2011 Elsevier Ltd. All rights reserved.

Activated Biological Filters (ABF Towers). Student Manual. Biological Treatment Process Control.

ERIC Educational Resources Information Center

Wooley, John F.

This student manual contains textual material for a two-lesson unit on activated bio-filters (ABF). The first lesson (the sewage treatment plant) examines those process units that are unique to the ABF system. The lesson includes a review of the structural components of the ABF system and their functions and a discussion of several operational…

UNDERSTANDINGS OF BSCS BIOLOGY STUDENTS AS DETERMINED BY INSTRUCTIONAL TESTS.

ERIC Educational Resources Information Center

ROBINSON, JAMES T.

EIGHT INSTRUCTIONAL TESTS SPANNED THE CURRICULUM OF ONE YEAR OF BIOLOGY STUDY. THE FIRST CONCERNED THE NATURE OF SCIENCE INCLUDED 4 AREAS OF EMPHASIS--THE NATURE AND FUNCTION OF HYPOTHESIS, THE IDEA OF CONTROLS IN EXPERIMENTS, INTERPRETATION OF GRAPHED DATA, AND THE NATURE OF DATA. THE SECOND TEST WAS DESIGNED TO SHOW AN UNDERSTANDING OF…

Automated quantitative assessment of proteins' biological function in protein knowledge bases.

PubMed

Mayr, Gabriele; Lepperdinger, Günter; Lackner, Peter

2008-01-01

Primary protein sequence data are archived in databases together with information regarding corresponding biological functions. In this respect, UniProt/Swiss-Prot is currently the most comprehensive collection and it is routinely cross-examined when trying to unravel the biological role of hypothetical proteins. Bioscientists frequently extract single entries and further evaluate those on a subjective basis. In lieu of a standardized procedure for scoring the existing knowledge regarding individual proteins, we here report about a computer-assisted method, which we applied to score the present knowledge about any given Swiss-Prot entry. Applying this quantitative score allows the comparison of proteins with respect to their sequence yet highlights the comprehension of functional data. pfs analysis may be also applied for quality control of individual entries or for database management in order to rank entry listings.

Functional classification of schizophrenia using feed forward neural networks.

PubMed

Jafri, Madiha J; Calhoun, Vince D

2006-01-01

In medicine, the nature of an illness is often determined through behavioral or biological markers. The process of diagnosis becomes difficult when dealing with mental disorders since they rely primarily on behavioral markers. Schizophrenia is an example of a complex mental disorder that relies on aberrant behavior such as auditory hallucinations, dampening of emotions, paranoia, etc. This research is an attempt to determine a biological marker for schizophrenia through the use of functional magnetic resonance imaging (fMRI). In this paper, we propose a method of classification of schizophrenia and healthy controls, using a neural network approach and functional brain 'modes'estimated from resting state data using independent component analysis. A reliable technique for discriminating schizophrenia based upon fMRI would be a significant advance and may also provide additional information about the biological implications of mental illness.

Physical models have gender-specific effects on student understanding of protein structure-function relationships.

PubMed

Forbes-Lorman, Robin M; Harris, Michelle A; Chang, Wesley S; Dent, Erik W; Nordheim, Erik V; Franzen, Margaret A

2016-07-08

Understanding how basic structural units influence function is identified as a foundational/core concept for undergraduate biological and biochemical literacy. It is essential for students to understand this concept at all size scales, but it is often more difficult for students to understand structure-function relationships at the molecular level, which they cannot as effectively visualize. Students need to develop accurate, 3-dimensional mental models of biomolecules to understand how biomolecular structure affects cellular functions at the molecular level, yet most traditional curricular tools such as textbooks include only 2-dimensional representations. We used a controlled, backward design approach to investigate how hand-held physical molecular model use affected students' ability to logically predict structure-function relationships. Brief (one class period) physical model use increased quiz score for females, whereas there was no significant increase in score for males using physical models. Females also self-reported higher learning gains in their understanding of context-specific protein function. Gender differences in spatial visualization may explain the gender-specific benefits of physical model use observed. © 2016 The Authors Biochemistry and Molecular Biology Education published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 44(4):326-335, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

Multifunctional ferromagnetic disks for modulating cell function

PubMed Central

Vitol, Elina A.; Novosad, Valentyn; Rozhkova, Elena A.

2013-01-01

In this work, we focus on the methods for controlling cell function with ferromagnetic disk-shaped particles. We will first review the history of magnetically assisted modulation of cell behavior and applications of magnetic particles for studying physical properties of a cell. Then, we consider the biological applications of the microdisks such as the method for induction of cancer cell apoptosis, controlled drug release, hyperthermia and MRI imaging. PMID:23766544

The effect of temperature on the functional response of Phytoseiulus persimilis (Acari: Phytoseiidae).

PubMed

Skirvin, David J; Fenlon, John S

2003-01-01

Environmental variables, such as temperature, are important in determining the efficiency of biological control in ornamental crops. This paper examines the effect of temperature on the functional response of adult female Phytoseiulus persimilis to eggs of the spider mite, Tetranychus urticae. The functional response was determined using a new functional response assay technique with plant stems as an arena, rather than leaf discs. The use of plant stems allows the influence that plant structure has on predation to be incorporated into the assay. Control assays were also used (without predators) to estimate natural losses of prey. The data were analysed using a binomial model, with the use of Abbot's formula to correct for the losses in the controls. A combined equation to describe the effect of temperature and prey density on the predation rate of Phytoseiulus persimilis was derived. The results showed that more prey are eaten as the temperature increases from 15 degrees C to 25 degrees C, but the number of prey eaten then declines at 30 degrees C, although not to the levels seen at 20 degrees C. The implication of these results for biological control in ornamental crops, where the temperature can often exceed 30 degrees C, is discussed.

Conciliation biology: the eco-evolutionary management of permanently invaded biotic systems

PubMed Central

Carroll, Scott P

2011-01-01

Biotic invaders and similar anthropogenic novelties such as domesticates, transgenics, and cancers can alter ecology and evolution in environmental, agricultural, natural resource, public health, and medical systems. The resulting biological changes may either hinder or serve management objectives. For example, biological control and eradication programs are often defeated by unanticipated resistance evolution and by irreversibility of invader impacts. Moreover, eradication may be ill-advised when nonnatives introduce beneficial functions. Thus, contexts that appear to call for eradication may instead demand managed coexistence of natives with nonnatives, and yet applied biologists have not generally considered the need to manage the eco-evolutionary dynamics that commonly result from interactions of natives with nonnatives. Here, I advocate a conciliatory approach to managing systems where novel organisms cannot or should not be eradicated. Conciliatory strategies incorporate benefits of nonnatives to address many practical needs including slowing rates of resistance evolution, promoting evolution of indigenous biological control, cultivating replacement services and novel functions, and managing native–nonnative coevolution. Evolutionary links across disciplines foster cohesion essential for managing the broad impacts of novel biotic systems. Rather than signaling defeat, conciliation biology thus utilizes the predictive power of evolutionary theory to offer diverse and flexible pathways to more sustainable outcomes. PMID:25567967

Electronic control of H+ current in a bioprotonic device with Gramicidin A and Alamethicin

NASA Astrophysics Data System (ADS)

Hemmatian, Zahra; Keene, Scott; Josberger, Erik; Miyake, Takeo; Arboleda, Carina; Soto-Rodríguez, Jessica; Baneyx, François; Rolandi, Marco

2016-10-01

In biological systems, intercellular communication is mediated by membrane proteins and ion channels that regulate traffic of ions and small molecules across cell membranes. A bioelectronic device with ion channels that control ionic flow across a supported lipid bilayer (SLB) should therefore be ideal for interfacing with biological systems. Here, we demonstrate a biotic-abiotic bioprotonic device with Pd contacts that regulates proton (H+) flow across an SLB incorporating the ion channels Gramicidin A (gA) and Alamethicin (ALM). We model the device characteristics using the Goldman-Hodgkin-Katz (GHK) solution to the Nernst-Planck equation for transport across the membrane. We derive the permeability for an SLB integrating gA and ALM and demonstrate pH control as a function of applied voltage and membrane permeability. This work opens the door to integrating more complex H+ channels at the Pd contact interface to produce responsive biotic-abiotic devices with increased functionality.

Tetrazine ligation for chemical proteomics.

PubMed

Kang, Kyungtae; Park, Jongmin; Kim, Eunha

2016-01-01

Determining small molecule-target protein interaction is essential for the chemical proteomics. One of the most important keys to explore biological system in chemical proteomics field is finding first-class molecular tools. Chemical probes can provide great spatiotemporal control to elucidate biological functions of proteins as well as for interrogating biological pathways. The invention of bioorthogonal chemistry has revolutionized the field of chemical biology by providing superior chemical tools and has been widely used for investigating the dynamics and function of biomolecules in live condition. Among 20 different bioorthogonal reactions, tetrazine ligation has been spotlighted as the most advanced bioorthogonal chemistry because of their extremely faster kinetics and higher specificity than others. Therefore, tetrazine ligation has a tremendous potential to enhance the proteomic research. This review highlights the current status of tetrazine ligation reaction as a molecular tool for the chemical proteomics.

Biotechnological synthesis of functional nanomaterials.

PubMed

Lloyd, Jonathan R; Byrne, James M; Coker, Victoria S

2011-08-01

Biological systems, especially those using microorganisms, have the potential to offer cheap, scalable and highly tunable green synthetic routes for the production of the latest generation of nanomaterials. Recent advances in the biotechnological synthesis of functional nano-scale materials are described. These nanomaterials range from catalysts to novel inorganic antimicrobials, nanomagnets, remediation agents and quantum dots for electronic and optical devices. Where possible, the roles of key biological macromolecules in controlling production of the nanomaterials are highlighted, and also technological limitations that must be addressed for widespread implementation are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

Augmenting the efficacy of fungal and mycotoxin control via chemosensitization

USDA-ARS?s Scientific Manuscript database

Antimycotic chemosensitization could serve as an effective method for control of fungal pathogens. In a chemo-biological platform to enhance antimycotic susceptibility of fungi or to overcome fungal tolerance to conventional antimycotic agents, the model yeast S. cerevisiae could be a functional too...

Functionalized Polymeric Membrane with Enhanced Mechanical and Biological Properties to Control the Degradation of Magnesium Alloy.

PubMed

Wong, Hoi Man; Zhao, Ying; Leung, Frankie K L; Xi, Tingfei; Zhang, Zhixiong; Zheng, Yufeng; Wu, Shuilin; Luk, Keith D K; Cheung, Kenneth M C; Chu, Paul K; Yeung, Kelvin W K

2017-04-01

To achieve enhanced biological response and controlled degradation of magnesium alloy, a modified biodegradable polymer coating called polycaprolactone (PCL) is fabricated by a thermal approach in which the heat treatment neither alters the chemical composition of the PCL membrane nor the rate of magnesium ion release, pH value, or weight loss, compared with the untreated sample. The changes in the crystallinity, hydrophilicity, and oxygen content of heat-treated PCL coating not only improve the mechanical adhesion strength between the coating and magnesium substrate but also enhance the biological properties. Moreover, the thermally modified sample can lead to higher spreading and elongation of osteoblasts, due to the enhanced hydrophilicity and CO to CO functional group ratio. In the analyses of microcomputed tomography from one to four weeks postoperation, the total volume of new bone formation on the heat-treated sample is 10%-35% and 70%-90% higher than that of the untreated and uncoated controls, respectively. Surprisingly, the indentation modulus of the newly formed bone adjacent to the heat-treated sample is ≈20% higher than that of both controls. These promising results reveal the clinical potential of the modified PCL coating on magnesium alloy in orthopedic applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Compartmentalization of superoxide dismutase 1 (SOD1G93A) aggregates determines their toxicity

PubMed Central

Weisberg, Sarah J.; Lyakhovetsky, Roman; Werdiger, Ayelet-chen; Gitler, Aaron D.; Soen, Yoav; Kaganovich, Daniel

2012-01-01

Neurodegenerative diseases constitute a class of illnesses marked by pathological protein aggregation in the brains of affected individuals. Although these disorders are invariably characterized by the degeneration of highly specific subpopulations of neurons, protein aggregation occurs in all cells, which indicates that toxicity arises only in particular cell biological contexts. Aggregation-associated disorders are unified by a common cell biological feature: the deposition of the culprit proteins in inclusion bodies. The precise function of these inclusions remains unclear. The starting point for uncovering the origins of disease pathology must therefore be a thorough understanding of the general cell biological function of inclusions and their potential role in modulating the consequences of aggregation. Here, we show that in human cells certain aggregate inclusions are active compartments. We find that toxic aggregates localize to one of these compartments, the juxtanuclear quality control compartment (JUNQ), and interfere with its quality control function. The accumulation of SOD1G93A aggregates sequesters Hsp70, preventing the delivery of misfolded proteins to the proteasome. Preventing the accumulation of SOD1G93A in the JUNQ by enhancing its sequestration in an insoluble inclusion reduces the harmful effects of aggregation on cell viability. PMID:22967507

Sucrose metabolism gene families and their biological functions

PubMed Central

Jiang, Shu-Ye; Chi, Yun-Hua; Wang, Ji-Zhou; Zhou, Jun-Xia; Cheng, Yan-Song; Zhang, Bao-Lan; Ma, Ali; Vanitha, Jeevanandam; Ramachandran, Srinivasan

2015-01-01

Sucrose, as the main product of photosynthesis, plays crucial roles in plant development. Although studies on general metabolism pathway were well documented, less information is available on the genome-wide identification of these genes, their expansion and evolutionary history as well as their biological functions. We focused on four sucrose metabolism related gene families including sucrose synthase, sucrose phosphate synthase, sucrose phosphate phosphatase and UDP-glucose pyrophosphorylase. These gene families exhibited different expansion and evolutionary history as their host genomes experienced differentiated rates of the whole genome duplication, tandem and segmental duplication, or mobile element mediated gene gain and loss. They were evolutionarily conserved under purifying selection among species and expression divergence played important roles for gene survival after expansion. However, we have detected recent positive selection during intra-species divergence. Overexpression of 15 sorghum genes in Arabidopsis revealed their roles in biomass accumulation, flowering time control, seed germination and response to high salinity and sugar stresses. Our studies uncovered the molecular mechanisms of gene expansion and evolution and also provided new insight into the role of positive selection in intra-species divergence. Overexpression data revealed novel biological functions of these genes in flowering time control and seed germination under normal and stress conditions. PMID:26616172

Carotenoids and their conversion products in the control of adipocyte function, adiposity and obesity.

PubMed

Luisa Bonet, M; Canas, Jose A; Ribot, Joan; Palou, Andreu

2015-04-15

A novel perspective of the function of carotenoids and carotenoid-derived products - including, but not restricted to, the retinoids - is emerging in recent years which connects these compounds to the control of adipocyte biology and body fat accumulation, with implications for the management of obesity, diabetes and cardiovascular disease. Cell and animal studies indicate that carotenoids and carotenoids derivatives can reduce adiposity and impact key aspects of adipose tissue biology including adipocyte differentiation, hypertrophy, capacity for fatty acid oxidation and thermogenesis (including browning of white adipose tissue) and secretory function. Epidemiological studies in humans associate higher dietary intakes and serum levels of carotenoids with decreased adiposity. Specifically designed human intervention studies, though still sparse, indicate a beneficial effect of carotenoid supplementation in the accrual of abdominal adiposity. The objective of this review is to summarize recent findings in this area, place them in physiological contexts, and provide likely regulatory schemes whenever possible. The focus will be on the effects of carotenoids as nutritional regulators of adipose tissue biology and both animal and human studies, which support a role of carotenoids and retinoids in the prevention of abdominal adiposity. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

[Principles of management in biological infections].

PubMed

Płusa, Tadeusz

2012-11-01

The effectiveness of the management in respiratory infection is depending on the nature of the biological pathogen and the immune status of the patient. For this reason, providing assistance to victims the organ function support, similarly as defining the pathogen and targeted antibiotic therapy should be applied. Available diagnostic tests provide rapid ability to identify the pathogen and antibiotics are able to control infection. Lack of efficacy of treatment may indicate the diversity of the pathogen than previously known and raises suspicion of biological warfare pathogen.

Can the invasive earthworm, Amynthas agrestis, be controlled with prescribed fire?

Treesearch

Hiroshi Ikeda; Mac A. Callaham Jr.; Joseph J. O' Brien; Benjamin S. Hornsby; Evelyn S. Wenk

2015-01-01

Biological invasions are one of the most significant global-scale problems caused by human activities. Earthworms function as ecosystem engineers in soil ecosystems because their feeding and burrowing activities fundamentally change the physical and biological characteristics of the soils they inhabit. As a result of this “engineering,” earthworm invasions can have...

The Temperature Optima and Temperature Sensitivity of Soil Respiration Explained By Macromolecular Rate Theory (MMRT).

NASA Astrophysics Data System (ADS)

Schipper, L. A.; O'Neill, T.; Arcus, V. L.

2014-12-01

One of the most fundamental factors controlling all biological and chemical processes is changing temperature. Temperature dependence was originally described by the Arrhenius function in the 19th century. This function provides an excellent description of chemical reaction rates. However, the Arrhenius function does not predict the temperature optimum of biological rates that is clearly evident in laboratory and field measurements. Previously, the temperature optimum of biological processes has been ascribed to denaturation of enzymes but the observed temperature optima in soil are often rather modest, occurring at about 40-50°C and generally less than recognised temperatures for protein unfolding. We have modified the Arrhenius function incorporating a temperature-dependent activation energy derived directly from first principles from thermodynamics of macromolecules. MacroMolecular Rate Theory (MMRT) accounts for large changes in the flexibility of enzymes during catalysis that result in changes in heat capacity (ΔC‡p) of the enzyme during the reaction. MMRT predicts an initially Arrhenius-like response followed by a temperature optimum without the need for enzyme denaturation (Hobbs et al., 2013. ACS Chemical Biology. 8: 2388-2393). Denaturation, of course, occurs at much higher temperatures. We have shown that MMRT fits biogeochemical data collected from laboratory and field studies with important implications for changes in absolute temperature sensitivity as temperature rises (Schipper et al., 2014. Global Change Biology). As the temperature optimum is approached the absolute temperature sensitivity of biological processes decreases to zero. Consequently, the absolute temperature-sensitivity of soil biological processes depends on both the change in ecosystem temperature and the temperature optimum of the biological process. MMRT also very clearly explains why Q10 values decline with increasing temperature more quickly than would be predicted from the Arrhenius function. Temperature optima of many soil biological processes including respiration are very poorly documented but would lead to a better understanding of how soil systems will respond to increasing global temperatures.

Bioengineering approaches to controlled protein delivery.

PubMed

Kobsa, Serge; Saltzman, W Mark

2008-05-01

Proteins are of crucial importance in all biologic organisms, in terms of both structure and function. Their deficits play central roles in many pathologic states, and their potential as powerful therapeutic agents has been widely recognized. Many issues, however, exist in delivery of biologically active proteins to target tissues and organs. Recent advances in biomedical engineering have lead to development of advanced techniques for controlled delivery of peptides and proteins, paving the way for their efficient use in treating human injury and disease. With a particular emphasis on most recent advances, this review discusses currently available techniques for controlled delivery of proteins and considers future research directions.

Biological dysrhythm in remitted bipolar I disorder.

PubMed

Iyer, Aishwarya; Palaniappan, Pradeep

2017-12-01

Recent treatment guidelines support treatment of biological rhythm abnormalities as a part of treatment of bipolar disorder, but still, literature examining various domains (Sleep, Activity, Social, and Eating) of biological rhythm and its clinical predictors are less. The main aim of our study is to compare various domains of biological rhythm among remitted bipolar I subjects and healthy controls. We also explored for any association between clinical variables and biological rhythm among bipolar subjects. 40 subjects with Bipolar I disorder and 40 healthy controls who met inclusion and exclusion criteria were recruited for the study. Diagnoses were ascertained by a qualified psychiatrist using MINI 5.0. Sociodemographic details, biological rhythm (BRIAN-Biological Rhythm Interview of assessment in Neuropsychiatry) and Sleep functioning (PSQI- Pittsburgh Sleep Quality Index) were assessed in all subjects. Mean age of the Bipolar subjects and controls were 41.25±11.84years and 38.25±11.25 years respectively. Bipolar subjects experienced more biological rhythm disturbance when compared to healthy controls (total BRIAN score being 34.25±9.36 vs 28.2±6.53) (p=0.002). Subsyndromal depressive symptoms (HDRS) had significant positive correlation with BRIAN global scores(r=0.368, p=0.02). Linear regression analysis showed that number of episodes which required hospitalization (β=0.601, t=3.106, P=0.004), PSQI (β=0.394, t=2.609, p=0.014), HDRS (β=0.376, t=2.34, t=0.036) explained 31% of variance in BRIAN scores in remitted bipolar subjects. Biological rhythm disturbances seem to persist even after clinical remission of bipolar illness. More studies to look into the impact of subsyndromal depressive symptoms on biological rhythm are needed. Copyright © 2017 Elsevier B.V. All rights reserved.

Structure and function of indigenous antibiotic-producing microbial communities in the rhizosphere of wheat

USDA-ARS?s Scientific Manuscript database

Phenazines are among the most widely studied metabolites produced by fluorescent Pseudomonas spp., not only because of their role in biological control but also because they function in biofilm formation, redox homeostasis, mineral acquisition, and, in some cases, pathogenesis. Despite the frequency...

Engineering the robustness of industrial microbes through synthetic biology.

PubMed

Zhu, Linjiang; Zhu, Yan; Zhang, Yanping; Li, Yin

2012-02-01

Microbial fermentations and bioconversions play a central role in the production of pharmaceuticals, enzymes and chemicals. To meet the demands of industrial production, it is desirable that microbes maintain a maximized carbon flux towards target metabolites regardless of fluctuations in intracellular or extracellular environments. This requires cellular systems that maintain functional stability and dynamic homeostasis in a given physiological state, or manipulate transitions between different physiological states. Stable maintenance or smooth transition can be achieved through engineering of dynamic controllability, modular and hierarchical organization, or functional redundancy, three key features of biological robustness in a cellular system. This review summarizes how synthetic biology can be used to improve the robustness of industrial microbes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Bioelectronic Sensors and Devices

NASA Astrophysics Data System (ADS)

Reed, Mark

Nanoscale electronic devices have recently enabled the ability to controllably probe biological systems, from the molecular to the cellular level, opening up new applications and understanding of biological function and response. This talk reviews some of the advances in the field, ranging from diagnostic and therapeutic applications, to cellular manipulation and response, to the emulation of biological response. In diagnostics, integrated nanodevice biosensors compatible with CMOS technology have achieved unprecedented sensitivity, enabling a wide range of label-free biochemical and macromolecule sensing applications down to femtomolar concentrations. These systems have demonstrated integrated assays of biomarkers at clinically important concentrations for both diagnostics and as a quantitative tool for drug design and discovery. Cellular level response can also be observed, including immune response function and dynamics. Finally, the field is beginning to create devices that emulate function, and the demonstration of a solid state artificial ion channel will be discussed.

Predicted Arabidopsis Interactome Resource and Gene Set Linkage Analysis: A Transcriptomic Analysis Resource.

PubMed

Yao, Heng; Wang, Xiaoxuan; Chen, Pengcheng; Hai, Ling; Jin, Kang; Yao, Lixia; Mao, Chuanzao; Chen, Xin

2018-05-01

An advanced functional understanding of omics data is important for elucidating the design logic of physiological processes in plants and effectively controlling desired traits in plants. We present the latest versions of the Predicted Arabidopsis Interactome Resource (PAIR) and of the gene set linkage analysis (GSLA) tool, which enable the interpretation of an observed transcriptomic change (differentially expressed genes [DEGs]) in Arabidopsis ( Arabidopsis thaliana ) with respect to its functional impact for biological processes. PAIR version 5.0 integrates functional association data between genes in multiple forms and infers 335,301 putative functional interactions. GSLA relies on this high-confidence inferred functional association network to expand our perception of the functional impacts of an observed transcriptomic change. GSLA then interprets the biological significance of the observed DEGs using established biological concepts (annotation terms), describing not only the DEGs themselves but also their potential functional impacts. This unique analytical capability can help researchers gain deeper insights into their experimental results and highlight prospective directions for further investigation. We demonstrate the utility of GSLA with two case studies in which GSLA uncovered how molecular events may have caused physiological changes through their collective functional influence on biological processes. Furthermore, we showed that typical annotation-enrichment tools were unable to produce similar insights to PAIR/GSLA. The PAIR version 5.0-inferred interactome and GSLA Web tool both can be accessed at http://public.synergylab.cn/pair/. © 2018 American Society of Plant Biologists. All Rights Reserved.

[Influence of hCG glycosylation on its functions in female reproduction].

PubMed

Oborná, I; Fingerová, H

To review contemporary knowledge of the hCG molecule, its isoforms and the importance of glycosylation. Biologic variants and glycoforms of hCG have different biological activities and functions related to the control of menstrual cycle, conception, gestation as well as gynaecologic and non-gynaecologic malignancies. A review. Department of Obstetrics and Gynaecology, University Hospital Olomouc. To present own experience and an overview of recent literature in molecular biology, clinical biochemistry and clinical practice. Recent knowledge of the role of hCG glycosylation in physiologic and pathologic events in female organism will provide a better understanding of regulation of processes like ovulation (co-operation of pituitary hCG with LH), implantation and hemochorial placentation (invasivity of hyperglycosylated hCG). Some biologic variants and isoforms of hCG are important for the prediction of certain pathologies of pregnancy, prenatal screening of inborn errors (free beta hCG) as well as in the treatment of infertility.

Darwinism and the cultural evolution of sports.

PubMed

De Block, Andreas; Dewitte, Siegfried

2009-01-01

This article outlines a Darwinian approach to sports that takes into account its profoundly cultural character and thereby overcomes the traditional nature-culture dichotomies in the sociology of sport. We argue that there are good reasons to view sports as culturally evolved signaling systems that serve a function similar to (biological) courtship rituals in other animals. Our approach combines the insights of evolutionary psychology, which states that biological adaptations determine the boundaries for the types of sport that are possible, and pure cultural theories, which describe the mechanism of cultural evolution without referring to sport's biological bases. Several biological and cultural factors may moderate the direct effect that signaling value has on a sport's viability or popularity. Social learning underlies many aspects of the cultural control of sports, and sports have evolved new cultural functions more-or-less unrelated to mate choice as cultural evolution itself became important in humans.

Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport.

PubMed

Howard, Rebecca J; Carnevale, Vincenzo; Delemotte, Lucie; Hellmich, Ute A; Rothberg, Brad S

2018-04-01

Ion translocation across biological barriers is a fundamental requirement for life. In many cases, controlling this process-for example with neuroactive drugs-demands an understanding of rapid and reversible structural changes in membrane-embedded proteins, including ion channels and transporters. Classical approaches to electrophysiology and structural biology have provided valuable insights into several such proteins over macroscopic, often discontinuous scales of space and time. Integrating these observations into meaningful mechanistic models now relies increasingly on computational methods, particularly molecular dynamics simulations, while surfacing important challenges in data management and conceptual alignment. Here, we seek to provide contemporary context, concrete examples, and a look to the future for bridging disciplinary gaps in biological ion transport. This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin McIlwain. Copyright © 2017 Elsevier B.V. All rights reserved.

Quantifying control effort of biological and technical movements: an information-entropy-based approach.

PubMed

Haeufle, D F B; Günther, M; Wunner, G; Schmitt, S

2014-01-01

In biomechanics and biorobotics, muscles are often associated with reduced movement control effort and simplified control compared to technical actuators. This is based on evidence that the nonlinear muscle properties positively influence movement control. It is, however, open how to quantify the simplicity aspect of control effort and compare it between systems. Physical measures, such as energy consumption, stability, or jerk, have already been applied to compare biological and technical systems. Here a physical measure of control effort based on information entropy is presented. The idea is that control is simpler if a specific movement is generated with less processed sensor information, depending on the control scheme and the physical properties of the systems being compared. By calculating the Shannon information entropy of all sensor signals required for control, an information cost function can be formulated allowing the comparison of models of biological and technical control systems. Exemplarily applied to (bio-)mechanical models of hopping, the method reveals that the required information for generating hopping with a muscle driven by a simple reflex control scheme is only I=32 bits versus I=660 bits with a DC motor and a proportional differential controller. This approach to quantifying control effort captures the simplicity of a control scheme and can be used to compare completely different actuators and control approaches.

Membrane Protein Incorporation into Nano-Bioelectronics: An insight into Rhodopsin Controlled SiNW-FET Devices

NASA Astrophysics Data System (ADS)

Tunuguntla, Ramya

Biological systems use different energy sources to interact with their environments by creating ion gradients, membrane electric potentials, or a proton motive force to accomplish strikingly complex tasks on the nanometer length scale, such as energy harvesting, and whole organism replication. Most of this activity involves a vast arsenal of active and passive ion channels, membrane receptors and ion pumps that mediate complex and precise transport across biological membranes. Despite the remarkable rate of progress exhibited by modern microelectronic devices, they still cannot compete with the efficiency and precision of biological systems on the component level. At the same time, the sophistication of these molecular machines provides an excellent opportunity to use them in hybrid bioelectronic devices where such a combination could deliver enhanced electronic functionality and enable seamless bi-directional interfaces between man-made and biological assemblies. Artificial membrane systems allow researchers to study the structure and function of membrane proteins in a matrix that approximates their natural environment and to integrate these proteins in ex-vivo devices such as electronic biosensors, thin-film protein arrays, or bio-fuel cells. Since most membrane proteins have vectorial functions, both functional studies and applications require effective control over protein orientation within a lipid bilayer. In our work, we have explored the role of the bilayer surface charge in determining transmembrane protein orientation and functionality during formation of proteoliposomes. We reconstituted a model vectorial ion pump, proteorhodopsin, in liposomes of opposite charges and varying charge densities and determined the resultant protein orientation. Antibody-binding assay and proteolysis of proteoliposomes showed physical evidence of preferential orientation, and functional assays verified vectorial nature of ion transport in this system. Our results indicate that the manipulation of lipid composition can indeed control orientation of an asymmetrically charged membrane protein, proteorhodopsin, in liposomes. One-dimensional inorganic nanostructures, which have critical dimensions comparable to the sizes of biological molecules, form an excellent materials platform for building such integrated structures. Researchers already use silicon nanowire-based field effect transistors functionalized with molecular recognition sites in a diverse array of biosensors. In our group, we have been developing a platform for integration of membrane protein functionality and electronic devices using a 1-D phospholipid bilayer device architecture. In these devices, the membrane proteins reside within the lipid bilayer that covers a nanowire channel of a field-effect transistor. This lipid bilayer performs several functions: it shields the nanowire from the solution species; it serves as a native-like environment for membrane proteins and preserves their functionality, integrity, and even vectorality. In this work, we show that a 1-D bilayer device incorporating a rhodopsin proton pump allows us to couple light-driven proton transport to a bioelectronic circuit. We also report that we were able to adapt another distinctive feature of biological signal processing---their widespread use of modifiers, co-factors, and mediator molecules---to regulate and fine-tune the operational characteristics of the bioelectronic device. In our example, we use co-assembly of protein channels and ionophores in the 1-D bilayer to modify the device output levels and response time.

Constructing biological pathway models with hybrid functional Petri nets.

PubMed

Doi, Atsushi; Fujita, Sachie; Matsuno, Hiroshi; Nagasaki, Masao; Miyano, Satoru

2004-01-01

In many research projects on modeling and analyzing biological pathways, the Petri net has been recognized as a promising method for representing biological pathways. From the pioneering works by Reddy et al., 1993, and Hofestädt, 1994, that model metabolic pathways by traditional Petri net, several enhanced Petri nets such as colored Petri net, stochastic Petri net, and hybrid Petri net have been used for modeling biological phenomena. Recently, Matsuno et al., 2003b, introduced the hybrid functional Petri net (HFPN) in order to give a more intuitive and natural modeling method for biological pathways than these existing Petri nets. Although the paper demonstrates the effectiveness of HFPN with two examples of gene regulation mechanism for circadian rhythms and apoptosis signaling pathway, there has been no detailed explanation about the method of HFPN construction for these examples. The purpose of this paper is to describe method to construct biological pathways with the HFPN step-by-step. The method is demonstrated by the well-known glycolytic pathway controlled by the lac operon gene regulatory mechanism.

Constructing biological pathway models with hybrid functional petri nets.

PubMed

Doi, Atsushi; Fujita, Sachie; Matsuno, Hiroshi; Nagasaki, Masao; Miyano, Satoru

2011-01-01

In many research projects on modeling and analyzing biological pathways, the Petri net has been recognized as a promising method for representing biological pathways. From the pioneering works by Reddy et al., 1993, and Hofestädt, 1994, that model metabolic pathways by traditional Petri net, several enhanced Petri nets such as colored Petri net, stochastic Petri net, and hybrid Petri net have been used for modeling biological phenomena. Recently, Matsuno et al., 2003b, introduced the hybrid functional Petri net (HFPN) in order to give a more intuitive and natural modeling method for biological pathways than these existing Petri nets. Although the paper demonstrates the effectiveness of HFPN with two examples of gene regulation mechanism for circadian rhythms and apoptosis signaling pathway, there has been no detailed explanation about the method of HFPN construction for these examples. The purpose of this paper is to describe method to construct biological pathways with the HFPN step-by-step. The method is demonstrated by the well-known glycolytic pathway controlled by the lac operon gene regulatory mechanism.

Unification of the macro- and microbiome in trophic ecology

USDA-ARS?s Scientific Manuscript database

Biological control is a key part of virtually any IPM program, and microbial bio-control agents represent particularly effective agents because of their capacity to be applied via conventional spray application methods. We are showing that fungi function just as arthropods do in the food web—the fun...

Influence of Temperature on the Dynamic Structures of Psychrophilic Small Heat Shock Proteins

DTIC Science & Technology

2010-02-27

Fibrils Controls Their Smallest Possible Fragment Size Journal of Molecular Biology 376 (4) 1155-1167. Robb, FT and P. Laksanalamai. 2008. Thermophilic ...Protein-Folding Systems pp 55-71 in Thermophiles : Biology and Technology at High Temperatures eds: Frank Robb, Garabed Antranikian, Dennis Grogan...functions by complementation and mutational analysis. 1. Enzyme salvage and refolding experiments. We used bovine glutamate dehydrogenase (a labile

Conformational Transitions in Molecular Systems

NASA Astrophysics Data System (ADS)

Bachmann, M.; Janke, W.

2008-11-01

Proteins are the "work horses" in biological systems. In almost all functions specific proteins are involved. They control molecular transport processes, stabilize the cell structure, enzymatically catalyze chemical reactions; others act as molecular motors in the complex machinery of molecular synthetization processes. Due to their significance, misfolds and malfunctions of proteins typically entail disastrous diseases, such as Alzheimer's disease and bovine spongiform encephalopathy (BSE). Therefore, the understanding of the trinity of amino acid composition, geometric structure, and biological function is one of the most essential challenges for the natural sciences. Here, we glance at conformational transitions accompanying the structure formation in protein folding processes.

The Effect of Acclydine in Chronic Fatigue Syndrome: A Randomized Controlled Trial

PubMed Central

The, Gerard K. H; Bleijenberg, Gijs; van der Meer, Jos W. M

2007-01-01

Objectives: It is unclear whether insulin-like growth factor (IGF) function is involved in the pathophysiology of chronic fatigue syndrome (CFS). Unpublished data and reports in patient organization newsletters suggest that Acclydine, a food supplement, could be effective in the treatment of CFS by increasing biologically active IGF1 levels. Here we aimed to measure the IGF1 and IGF binding protein (IGFBP) 3 status of CFS patients compared to age- and gender-matched neighborhood controls, and to assess the effect of Acclydine on fatigue severity, functional impairment, and biologically active IGF1 level (IGFBP3/IGF1 ratio). Design: A randomized, placebo-controlled, double-blind clinical trial. Setting: Radboud University Nijmegen Medical Centre, The Netherlands. Participants: Fifty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention criteria for CFS. IGF status of 22 CFS patients was compared to that of 22 healthy age- and gender-matched neighborhood control individuals. Intervention: Acclydine or placebo for 14 wk. Outcome measures: Outcomes were fatigue severity (Checklist Individual Strength, subscale fatigue severity [CIS-fatigue]), functional impairment (Sickness Impact Profile-8 [SIP-8]), and biologically active IGF1 serum concentrations. Analyses were on an intention-to-treat basis. Results: There was no difference in IGF status in 22 CFS patients compared to healthy age- and gender-matched control individuals. Treatment with Acclydine did not result in significant differences compared with the placebo group on any of the outcome measures: CIS-fatigue +1.1 (95% CI −4.4 to +6.5, p = 0.70), SIP-8 +59.1 (95% CI −201.7 to +319.8, p = 0.65), and IGFBP3/IGF1 ratio −0.5 (95% CI −2.8 to +1.7, p = 0.63). Conclusion: We found no differences in IGF1 status in CFS patients compared to healthy matched neighborhood controls. In addition, the results of this clinical trial do not demonstrate any benefit of Acclydine over placebo in the treatment of CFS. PMID:17525791

The effect of acclydine in chronic fatigue syndrome: a randomized controlled trial.

PubMed

The, Gerard K H; Bleijenberg, Gijs; van der Meer, Jos W M

2007-05-18

It is unclear whether insulin-like growth factor (IGF) function is involved in the pathophysiology of chronic fatigue syndrome (CFS). Unpublished data and reports in patient organization newsletters suggest that Acclydine, a food supplement, could be effective in the treatment of CFS by increasing biologically active IGF1 levels. Here we aimed to measure the IGF1 and IGF binding protein (IGFBP) 3 status of CFS patients compared to age- and gender-matched neighborhood controls, and to assess the effect of Acclydine on fatigue severity, functional impairment, and biologically active IGF1 level (IGFBP3/IGF1 ratio). A randomized, placebo-controlled, double-blind clinical trial. Radboud University Nijmegen Medical Centre, The Netherlands. Fifty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention criteria for CFS. IGF status of 22 CFS patients was compared to that of 22 healthy age- and gender-matched neighborhood control individuals. Acclydine or placebo for 14 wk. Outcomes were fatigue severity (Checklist Individual Strength, subscale fatigue severity [CIS-fatigue]), functional impairment (Sickness Impact Profile-8 [SIP-8]), and biologically active IGF1 serum concentrations. Analyses were on an intention-to-treat basis. There was no difference in IGF status in 22 CFS patients compared to healthy age- and gender-matched control individuals. Treatment with Acclydine did not result in significant differences compared with the placebo group on any of the outcome measures: CIS-fatigue +1.1 (95% CI -4.4 to +6.5, p = 0.70), SIP-8 +59.1 (95% CI -201.7 to +319.8, p = 0.65), and IGFBP3/IGF1 ratio -0.5 (95% CI -2.8 to +1.7, p = 0.63). We found no differences in IGF1 status in CFS patients compared to healthy matched neighborhood controls. In addition, the results of this clinical trial do not demonstrate any benefit of Acclydine over placebo in the treatment of CFS.

Strategies for Controlled Delivery of Biologics for Cartilage Repair

PubMed Central

Lam, Johnny; Lu, Steven; Kasper, F. Kurtis; Mikos, Antonios G.

2014-01-01

The delivery of biologics is an important component in the treatment of osteoarthritis and the functional restoration of articular cartilage. Numerous factors have been implicated in the cartilage repair process, but the uncontrolled delivery of these factors may not only reduce their full reparative potential and can also cause unwanted morphological effects. It is therefore imperative to consider the type of biologic to be delivered, the method of delivery, and the temporal as well as spatial presentation of the biologic to achieve the desired effect in cartilage repair. Additionally, the delivery of a single factor may not be sufficient in guiding neo-tissue formation, motivating recent research towards the delivery of multiple factors. This review will discuss the roles of various biologics involved in cartilage repair and the different methods of delivery for appropriate healing responses. A number of spatiotemporal strategies will then be emphasized for the controlled delivery of single and multiple bioactive factors in both in vitro and in vivo cartilage tissue engineering applications. PMID:24993610

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

Simulations of molecular self-assembled monolayers on surfaces: packing structures, formation processes and functions tuned by intermolecular and interfacial interactions.

PubMed

Wen, Jin; Li, Wei; Chen, Shuang; Ma, Jing

2016-08-17

Surfaces modified with a functional molecular monolayer are essential for the fabrication of nano-scale electronics or machines with novel physical, chemical, and/or biological properties. Theoretical simulation based on advanced quantum chemical and classical models is at present a necessary tool in the development, design, and understanding of the interfacial nanostructure. The nanoscale surface morphology, growth processes, and functions are controlled by not only the electronic structures (molecular energy levels, dipole moments, polarizabilities, and optical properties) of building units but also the subtle balance between intermolecular and interfacial interactions. The switchable surfaces are also constructed by introducing stimuli-responsive units like azobenzene derivatives. To bridge the gap between experiments and theoretical models, opportunities and challenges for future development of modelling of ferroelectricity, entropy, and chemical reactions of surface-supported monolayers are also addressed. Theoretical simulations will allow us to obtain important and detailed information about the structure and dynamics of monolayer modified interfaces, which will guide the rational design and optimization of dynamic interfaces to meet challenges of controlling optical, electrical, and biological functions.

Synthetic analog computation in living cells.

PubMed

Daniel, Ramiz; Rubens, Jacob R; Sarpeshkar, Rahul; Lu, Timothy K

2013-05-30

A central goal of synthetic biology is to achieve multi-signal integration and processing in living cells for diagnostic, therapeutic and biotechnology applications. Digital logic has been used to build small-scale circuits, but other frameworks may be needed for efficient computation in the resource-limited environments of cells. Here we demonstrate that synthetic analog gene circuits can be engineered to execute sophisticated computational functions in living cells using just three transcription factors. Such synthetic analog gene circuits exploit feedback to implement logarithmically linear sensing, addition, ratiometric and power-law computations. The circuits exhibit Weber's law behaviour as in natural biological systems, operate over a wide dynamic range of up to four orders of magnitude and can be designed to have tunable transfer functions. Our circuits can be composed to implement higher-order functions that are well described by both intricate biochemical models and simple mathematical functions. By exploiting analog building-block functions that are already naturally present in cells, this approach efficiently implements arithmetic operations and complex functions in the logarithmic domain. Such circuits may lead to new applications for synthetic biology and biotechnology that require complex computations with limited parts, need wide-dynamic-range biosensing or would benefit from the fine control of gene expression.

Preparation and Characterization of Biofunctionalized Inorganic Substrates.

PubMed

Dugger, Jason W; Webb, Lauren J

2015-09-29

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

Functional Role of PPARs in Ruminants: Potential Targets for Fine-Tuning Metabolism during Growth and Lactation

PubMed Central

Chen, Shuowen; Khan, Muhammad J.; Loor, Juan J.

2013-01-01

Characterization and biological roles of the peroxisome proliferator-activated receptor (PPAR) isotypes are well known in monogastrics, but not in ruminants. However, a wealth of information has accumulated in little more than a decade on ruminant PPARs including isotype tissue distribution, response to synthetic and natural agonists, gene targets, and factors affecting their expression. Functional characterization demonstrated that, as in monogastrics, the PPAR isotypes control expression of genes involved in lipid metabolism, anti-inflammatory response, development, and growth. Contrary to mouse, however, the PPARγ gene network appears to controls milk fat synthesis in lactating ruminants. As in monogastrics, PPAR isotypes in ruminants are activated by long-chain fatty acids, therefore, making them ideal candidates for fine-tuning metabolism in this species via nutrients. In this regard, using information accumulated in ruminants and monogastrics, we propose a model of PPAR isotype-driven biological functions encompassing key tissues during the peripartal period in dairy cattle. PMID:23737762

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

Jawdy, Sara S.; Gunter, Lee E.; Engle, Nancy L.

Here, the biological function of the plant-microbiome system is the result of contributions from the host plant and microbiome members. In this work we study the function of a simplified community consisting of Pseudomonas and Burkholderia bacterial strains isolated from Populus hosts and inoculated on axenic Populus cutting in controlled laboratory conditions. Inoculation individually with either bacterial isolate increased root growth relative to uninoculated controls. Root area, photosynthetic efficiency, gene expression and metabolite expression data in individual and dual inoculated treatments indicate that the effects of these bacteria are unique and additive, suggesting that the function of a microbiome communitymore » may be predicted from the additive functions of the individual members.« less

75 FR 43190 - Statement of Organization, Functions, and Delegations of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-23

... human and animal health; (5) ensures scientific quality and ethical and regulatory compliance of center... investigations on the biology, ecology, and control of arthropod vectors of viral, rickettsial, and bacterial...

The Physical Microbe; An introduction to noise, control, and communication in the prokaryotic cell

NASA Astrophysics Data System (ADS)

Hagen, Stephen J.

2017-10-01

Physical biology is a fusion of biology and physics. This book narrows down the scope of physical biology by focusing on the microbial cell; exploring the physical phenomena of noise, feedback, and variability that arise in the cellular information-processing circuits used by bacteria. It looks at the microbe from a physics perspective, asking how the cell optimizes its function to live within the constraints of physics. It introduces a physical and information-based (as opposed to microbiological) perspective on communication and signalling between microbes.

Synthetic biology in mammalian cells: Next generation research tools and therapeutics

PubMed Central

Lienert, Florian; Lohmueller, Jason J; Garg, Abhishek; Silver, Pamela A

2014-01-01

Recent progress in DNA manipulation and gene circuit engineering has greatly improved our ability to programme and probe mammalian cell behaviour. These advances have led to a new generation of synthetic biology research tools and potential therapeutic applications. Programmable DNA-binding domains and RNA regulators are leading to unprecedented control of gene expression and elucidation of gene function. Rebuilding complex biological circuits such as T cell receptor signalling in isolation from their natural context has deepened our understanding of network motifs and signalling pathways. Synthetic biology is also leading to innovative therapeutic interventions based on cell-based therapies, protein drugs, vaccines and gene therapies. PMID:24434884

Genome-wide analysis of protein disorder in Arabidopsis thaliana: implications for plant environmental adaptation.

PubMed

Pietrosemoli, Natalia; García-Martín, Juan A; Solano, Roberto; Pazos, Florencio

2013-01-01

Intrinsically disordered proteins/regions (IDPs/IDRs) are currently recognized as a widespread phenomenon having key cellular functions. Still, many aspects of the function of these proteins need to be unveiled. IDPs conformational flexibility allows them to recognize and interact with multiple partners, and confers them larger interaction surfaces that may increase interaction speed. For this reason, molecular interactions mediated by IDPs/IDRs are particularly abundant in certain types of protein interactions, such as those of signaling and cell cycle control. We present the first large-scale study of IDPs in Arabidopsis thaliana, the most widely used model organism in plant biology, in order to get insight into the biological roles of these proteins in plants. The work includes a comparative analysis with the human proteome to highlight the differential use of disorder in both species. Results show that while human proteins are in general more disordered, certain functional classes, mainly related to environmental response, are significantly more enriched in disorder in Arabidopsis. We propose that because plants cannot escape from environmental conditions as animals do, they use disorder as a simple and fast mechanism, independent of transcriptional control, for introducing versatility in the interaction networks underlying these biological processes so that they can quickly adapt and respond to challenging environmental conditions.

Electronic control of H+ current in a bioprotonic device with Gramicidin A and Alamethicin

PubMed Central

Hemmatian, Zahra; Keene, Scott; Josberger, Erik; Miyake, Takeo; Arboleda, Carina; Soto-Rodríguez, Jessica; Baneyx, François; Rolandi, Marco

2016-01-01

In biological systems, intercellular communication is mediated by membrane proteins and ion channels that regulate traffic of ions and small molecules across cell membranes. A bioelectronic device with ion channels that control ionic flow across a supported lipid bilayer (SLB) should therefore be ideal for interfacing with biological systems. Here, we demonstrate a biotic–abiotic bioprotonic device with Pd contacts that regulates proton (H+) flow across an SLB incorporating the ion channels Gramicidin A (gA) and Alamethicin (ALM). We model the device characteristics using the Goldman–Hodgkin–Katz (GHK) solution to the Nernst–Planck equation for transport across the membrane. We derive the permeability for an SLB integrating gA and ALM and demonstrate pH control as a function of applied voltage and membrane permeability. This work opens the door to integrating more complex H+ channels at the Pd contact interface to produce responsive biotic–abiotic devices with increased functionality. PMID:27713411

From bacteria to mollusks: the principles underlying the biomineralization of iron oxide materials.

PubMed

Faivre, Damien; Godec, Tina Ukmar

2015-04-13

Various organisms possess a genetic program that enables the controlled formation of a mineral, a process termed biomineralization. The variety of biological material architectures is mind-boggling and arises from the ability of organisms to exert control over crystal nucleation and growth. The structure and composition of biominerals equip biomineralizing organisms with properties and functionalities that abiotically formed materials, made of the same mineral, usually lack. Therefore, elucidating the mechanisms underlying biomineralization and morphogenesis is of interdisciplinary interest to extract design principles that will enable the biomimetic formation of functional materials with similar capabilities. Herein, we summarize what is known about iron oxides formed by bacteria and mollusks for their magnetic and mechanical properties. We describe the chemical and biological machineries that are involved in controlling mineral precipitation and organization and show how these organisms are able to form highly complex structures under physiological conditions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Semiconductor nanowires: A platform for nanoscience and nanotechnology

PubMed Central

Lieber, Charles M.

2012-01-01

Advances in nanoscience and nanotechnology critically depend on the development of nanostructures whose properties are controlled during synthesis. We focus on this critical concept using semiconductor nanowires, which provide the capability through design and rational synthesis to realize unprecedented structural and functional complexity in building blocks as a platform material. First, a brief review of the synthesis of complex modulated nanowires in which rational design and synthesis can be used to precisely control composition, structure, and, most recently, structural topology is discussed. Second, the unique functional characteristics emerging from our exquisite control of nanowire materials are illustrated using several selected examples from nanoelectronics and nano-enabled energy. Finally, the remarkable power of nanowire building blocks is further highlighted through their capability to create unprecedented, active electronic interfaces with biological systems. Recent work pushing the limits of both multiplexed extracellular recording at the single-cell level and the first examples of intracellular recording is described, as well as the prospects for truly blurring the distinction between nonliving nanoelectronic and living biological systems. PMID:22707850

Engineering and control of biological systems: A new way to tackle complex diseases.

PubMed

Menolascina, Filippo; Siciliano, Velia; di Bernardo, Diego

2012-07-16

The ongoing merge between engineering and biology has contributed to the emerging field of synthetic biology. The defining features of this new discipline are abstraction and standardisation of biological parts, decoupling between parts to prevent undesired cross-talking, and the application of quantitative modelling of synthetic genetic circuits in order to guide their design. Most of the efforts in the field of synthetic biology in the last decade have been devoted to the design and development of functional gene circuits in prokaryotes and unicellular eukaryotes. Researchers have used synthetic biology not only to engineer new functions in the cell, but also to build simpler models of endogenous gene regulatory networks to gain knowledge of the "rules" governing their wiring diagram. However, the need for innovative approaches to study and modify complex signalling and regulatory networks in mammalian cells and multicellular organisms has prompted advances of synthetic biology also in these species, thus contributing to develop innovative ways to tackle human diseases. In this work, we will review the latest progress in synthetic biology and the most significant developments achieved so far, both in unicellular and multicellular organisms, with emphasis on human health. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Detecting genotypic variation among the single spore isolates of Pasteuria penetrans population occuring in Florida using SNP-based markers

USDA-ARS?s Scientific Manuscript database

Pasteuria penetrans is a naturally occurring soil-borne endospore-forming bacterium, which functions as a castrating parasite of plant-parasitic nematodes belonging to the genus Meloidogyne. Pasteuria penetrans is established as an effective biological control agent for control and management o...

Normal form from biological motion despite impaired ventral stream function.

PubMed

Gilaie-Dotan, S; Bentin, S; Harel, M; Rees, G; Saygin, A P

2011-04-01

We explored the extent to which biological motion perception depends on ventral stream integration by studying LG, an unusual case of developmental visual agnosia. LG has significant ventral stream processing deficits but no discernable structural cortical abnormality. LG's intermediate visual areas and object-sensitive regions exhibit abnormal activation during visual object perception, in contrast to area V5/MT+ which responds normally to visual motion (Gilaie-Dotan, Perry, Bonneh, Malach, & Bentin, 2009). Here, in three studies we used point light displays, which require visual integration, in adaptive threshold experiments to examine LG's ability to detect form from biological and non-biological motion cues. LG's ability to detect and discriminate form from biological motion was similar to healthy controls. In contrast, he was significantly deficient in processing form from non-biological motion. Thus, LG can rely on biological motion cues to perceive human forms, but is considerably impaired in extracting form from non-biological motion. Finally, we found that while LG viewed biological motion, activity in a network of brain regions associated with processing biological motion was functionally correlated with his V5/MT+ activity, indicating that normal inputs from V5/MT+ might suffice to activate his action perception system. These results indicate that processing of biologically moving form can dissociate from other form processing in the ventral pathway. Furthermore, the present results indicate that integrative ventral stream processing is necessary for uncompromised processing of non-biological form from motion. Copyright © 2011 Elsevier Ltd. All rights reserved.

Manipulating and Monitoring On-Surface Biological Reactions by Light-Triggered Local pH Alterations.

PubMed

Peretz-Soroka, Hagit; Pevzner, Alexander; Davidi, Guy; Naddaka, Vladimir; Kwiat, Moria; Huppert, Dan; Patolsky, Fernando

2015-07-08

Significant research efforts have been dedicated to the integration of biological species with electronic elements to yield smart bioelectronic devices. The integration of DNA, proteins, and whole living cells and tissues with electronic devices has been developed into numerous intriguing applications. In particular, the quantitative detection of biological species and monitoring of biological processes are both critical to numerous areas of medical and life sciences. Nevertheless, most current approaches merely focus on the "monitoring" of chemical processes taking place on the sensing surfaces, and little efforts have been invested in the conception of sensitive devices that can simultaneously "control" and "monitor" chemical and biological reactions by the application of on-surface reversible stimuli. Here, we demonstrate the light-controlled fine modulation of surface pH by the use of photoactive molecularly modified nanomaterials. Through the use of nanowire-based FET devices, we showed the capability of modulating the on-surface pH, by intensity-controlled light stimulus. This allowed us simultaneously and locally to control and monitor pH-sensitive biological reactions on the nanodevices surfaces, such as the local activation and inhibition of proteolytic enzymatic processes, as well as dissociation of antigen-antibody binding interactions. The demonstrated capability of locally modulating the on-surface effective pH, by a light stimuli, may be further applied in the local control of on-surface DNA hybridization/dehybridization processes, activation or inhibition of living cells processes, local switching of cellular function, local photoactivation of neuronal networks with single cell resolution and so forth.

The Center for Regenerative Biology and Medicine at Mount Desert Island Biological Laboratory

DTIC Science & Technology

2013-06-01

system through in vivo disruption of gene function. 15. SUBJECT TERMS limb regeneration Positional Memory Code Axolotl ...another selection factor to identify those genes that are similarly controlled in both Polypterus and axolotl samples. These comparisons revealed a...sequence IDs among Axolotl and Polypterus contigs that were up-regulated and down regulated greater than 2-fold between 0 and 7 dpa. (Left) The

Cellular Engineering with Membrane Fusogenic Liposomes to Produce Functionalized Extracellular Vesicles.

PubMed

Lee, Junsung; Lee, Hyoungjin; Goh, Unbyeol; Kim, Jiyoung; Jeong, Moonkyoung; Lee, Jean; Park, Ji-Ho

2016-03-23

Engineering of extracellular vesicles (EVs) without affecting biological functions remains a challenge, limiting the broad applications of EVs in biomedicine. Here, we report a method to equip EVs with various functional agents, including fluorophores, drugs, lipids, and bio-orthogonal chemicals, in an efficient and controlled manner by engineering parental cells with membrane fusogenic liposomes, while keeping the EVs intact. As a demonstration of how this method can be applied, we prepared EVs containing azide-lipids, and conjugated them with targeting peptides using copper-free click chemistry to enhance targeting efficacy to cancer cells. We believe that this liposome-based cellular engineering method will find utility in studying the biological roles of EVs and delivering therapeutic agents through their innate pathway.

Microvascular function in women with former gestational diabetes: A cohort study.

PubMed

Charwat-Resl, Silvia; Yarragudi, Rajashri; Heimbach, Moritz; Leitner, Karoline; Leutner, Michael; Gamper, Jutta; Giurgea, Georgiana-Aura; Mueller, Markus; Koppensteiner, Renate; Gschwandtner, Michael E; Kautzky-Willer, Alexandra; Schlager, Oliver

2017-05-01

In the long term, diabetes mellitus is potentially associated with the occurrence of microvascular damage. This study sought to assess whether a history of prior gestational diabetes mellitus is associated with long-term effects on the women's microcirculation. Within the scope of a long-term follow-up of the 'Viennese Post-Gestational Diabetes Project', women with prior gestational diabetes mellitus as well as women with previous pregnancy but with no history of gestational diabetes mellitus (controls) were enrolled in this cross-sectional study. Microvascular function was assessed by post-occlusive reactive hyperaemia using laser Doppler fluxmetry. Baseline perfusion, biological zero, peak perfusion, time to peak and recovery time were recorded and compared between both groups. Microvascular function was assessed in 55 women with prior gestational diabetes mellitus (46.1 ± 4.6 years) and 32 women with previous pregnancy but without prior gestational diabetes mellitus (42.9 ± 5.3 years). The mean period of time between delivery and the assessment of microvascular function was 16.2 ± 5.2 years in women with prior gestational diabetes mellitus group and 14.2 ± 4.8 years in controls. Regarding microvascular function, baseline perfusion, biological zero, peak perfusion, time to peak and recovery time did not differ between women with prior gestational diabetes mellitus and controls (all p > 0.05). In the long term, microvascular function appears not to be impaired in women with prior gestational diabetes mellitus.

A biochemical network can control formation of a synthetic material by sensing numerous specific stimuli

NASA Astrophysics Data System (ADS)

Hun Yeon, Ju; Chan, Karen Y. T.; Wong, Ting-Chia; Chan, Kelvin; Sutherland, Michael R.; Ismagilov, Rustem F.; Pryzdial, Edward L. G.; Kastrup, Christian J.

2015-05-01

Developing bio-compatible smart materials that assemble in response to environmental cues requires strategies that can discriminate multiple specific stimuli in a complex milieu. Synthetic materials have yet to achieve this level of sensitivity, which would emulate the highly evolved and tailored reaction networks of complex biological systems. Here we show that the output of a naturally occurring network can be replaced with a synthetic material. Exploiting the blood coagulation system as an exquisite biological sensor, the fibrin clot end-product was replaced with a synthetic material under the biological control of a precisely regulated cross-linking enzyme. The functions of the coagulation network remained intact when the material was incorporated. Clot-like polymerization was induced in indirect response to distinct small molecules, phospholipids, enzymes, cells, viruses, an inorganic solid, a polyphenol, a polysaccharide, and a membrane protein. This strategy demonstrates for the first time that an existing stimulus-responsive biological network can be used to control the formation of a synthetic material by diverse classes of physiological triggers.

The retinoblastoma tumor suppressor and stem cell biology.

PubMed

Sage, Julien

2012-07-01

Stem cells play a critical role during embryonic development and in the maintenance of homeostasis in adult individuals. A better understanding of stem cell biology, including embryonic and adult stem cells, will allow the scientific community to better comprehend a number of pathologies and possibly design novel approaches to treat patients with a variety of diseases. The retinoblastoma tumor suppressor RB controls the proliferation, differentiation, and survival of cells, and accumulating evidence points to a central role for RB activity in the biology of stem and progenitor cells. In some contexts, loss of RB function in stem or progenitor cells is a key event in the initiation of cancer and determines the subtype of cancer arising from these pluripotent cells by altering their fate. In other cases, RB inactivation is often not sufficient to initiate cancer but may still lead to some stem cell expansion, raising the possibility that strategies aimed at transiently inactivating RB might provide a novel way to expand functional stem cell populations. Future experiments dedicated to better understanding how RB and the RB pathway control a stem cell's decisions to divide, self-renew, or give rise to differentiated progeny may eventually increase our capacity to control these decisions to enhance regeneration or help prevent cancer development.

Impaired Perception of Biological Motion in Parkinson’s Disease

PubMed Central

Jaywant, Abhishek; Shiffrar, Maggie; Roy, Serge; Cronin-Golomb, Alice

2016-01-01

Objective We examined biological motion perception in Parkinson’s disease (PD). Biological motion perception is related to one’s own motor function and depends on the integrity of brain areas affected in PD, including posterior superior temporal sulcus. If deficits in biological motion perception exist, they may be specific to perceiving natural/fast walking patterns that individuals with PD can no longer perform, and may correlate with disease-related motor dysfunction. Method 26 non-demented individuals with PD and 24 control participants viewed videos of point-light walkers and scrambled versions that served as foils, and indicated whether each video depicted a human walking. Point-light walkers varied by gait type (natural, parkinsonian) and speed (0.5, 1.0, 1.5 m/s). Participants also completed control tasks (object motion, coherent motion perception), a contrast sensitivity assessment, and a walking assessment. Results The PD group demonstrated significantly less sensitivity to biological motion than the control group (p<.001, Cohen’s d=1.22), regardless of stimulus gait type or speed, with a less substantial deficit in object motion perception (p=.02, Cohen’s d=.68). There was no group difference in coherent motion perception. Although individuals with PD had slower walking speed and shorter stride length than control participants, gait parameters did not correlate with biological motion perception. Contrast sensitivity and coherent motion perception also did not correlate with biological motion perception. Conclusion PD leads to a deficit in perceiving biological motion, which is independent of gait dysfunction and low-level vision changes, and may therefore arise from difficulty perceptually integrating form and motion cues in posterior superior temporal sulcus. PMID:26949927

Invited review: gravitational biology of the neuromotor systems: a perspective to the next era

NASA Technical Reports Server (NTRS)

Edgerton, V. R.; Roy, R. R.

2000-01-01

Earth's gravity has had a significant impact on the designs of the neuromotor systems that have evolved. Early indications are that gravity also plays a key role in the ontogenesis of some of these design features. The purpose of the present review is not to assess and interpret a body of knowledge in the usual sense of a review but to look ahead, given some of the general concepts that have evolved and observations made to date, which can guide our future approach to gravitational biology. We are now approaching an era in gravitational biology during which well-controlled experiments can be conducted for sustained periods in a microgravity environment. Thus it is now possible to study in greater detail the role of gravity in phylogenesis and ontogenesis. Experiments can range from those conducted on the simplest levels of organization of the components that comprise the neuromotor system to those conducted on the whole organism. Generally, the impact of Earth's gravitational environment on living systems becomes more complex as the level of integration of the biological phenomenon of interest increases. Studies of the effects of gravitational vectors on neuromotor systems have and should continue to provide unique insight into these mechanisms that control and maintain neural control systems designed to function in Earth's gravitational environment. A number of examples are given of how a gravitational biology perspective can lead to a clearer understanding of neuromotor disorders. Furthermore, the technologies developed for spaceflight studies have contributed and should continue to contribute to studies of motor dysfunctions, such as spinal cord injury and stroke. Disorders associated with energy support and delivery systems and how these functions are altered by sedentary life styles at 1 G and by space travel in a microgravity environment are also discussed.

[A novel biologic electricity signal measurement based on neuron chip].

PubMed

Lei, Yinsheng; Wang, Mingshi; Sun, Tongjing; Zhu, Qiang; Qin, Ran

2006-06-01

Neuron chip is a multiprocessor with three pipeline CPU; its communication protocol and control processor are integrated in effect to carry out the function of communication, control, attemper, I/O, etc. A novel biologic electronic signal measurement network system is composed of intelligent measurement nodes with neuron chip at the core. In this study, the electronic signals such as ECG, EEG, EMG and BOS can be synthetically measured by those intelligent nodes, and some valuable diagnostic messages are found. Wavelet transform is employed in this system to analyze various biologic electronic signals due to its strong time-frequency ability of decomposing signal local character. Better effect is gained. This paper introduces the hardware structure of network and intelligent measurement node, the measurement theory and the signal figure of data acquisition and processing.

Protein interaction network topology uncovers melanogenesis regulatory network components within functional genomics datasets.

PubMed

Ho, Hsiang; Milenković, Tijana; Memisević, Vesna; Aruri, Jayavani; Przulj, Natasa; Ganesan, Anand K

2010-06-15

RNA-mediated interference (RNAi)-based functional genomics is a systems-level approach to identify novel genes that control biological phenotypes. Existing computational approaches can identify individual genes from RNAi datasets that regulate a given biological process. However, currently available methods cannot identify which RNAi screen "hits" are novel components of well-characterized biological pathways known to regulate the interrogated phenotype. In this study, we describe a method to identify genes from RNAi datasets that are novel components of known biological pathways. We experimentally validate our approach in the context of a recently completed RNAi screen to identify novel regulators of melanogenesis. In this study, we utilize a PPI network topology-based approach to identify targets within our RNAi dataset that may be components of known melanogenesis regulatory pathways. Our computational approach identifies a set of screen targets that cluster topologically in a human PPI network with the known pigment regulator Endothelin receptor type B (EDNRB). Validation studies reveal that these genes impact pigment production and EDNRB signaling in pigmented melanoma cells (MNT-1) and normal melanocytes. We present an approach that identifies novel components of well-characterized biological pathways from functional genomics datasets that could not have been identified by existing statistical and computational approaches.

Protein interaction network topology uncovers melanogenesis regulatory network components within functional genomics datasets

PubMed Central

2010-01-01

Background RNA-mediated interference (RNAi)-based functional genomics is a systems-level approach to identify novel genes that control biological phenotypes. Existing computational approaches can identify individual genes from RNAi datasets that regulate a given biological process. However, currently available methods cannot identify which RNAi screen "hits" are novel components of well-characterized biological pathways known to regulate the interrogated phenotype. In this study, we describe a method to identify genes from RNAi datasets that are novel components of known biological pathways. We experimentally validate our approach in the context of a recently completed RNAi screen to identify novel regulators of melanogenesis. Results In this study, we utilize a PPI network topology-based approach to identify targets within our RNAi dataset that may be components of known melanogenesis regulatory pathways. Our computational approach identifies a set of screen targets that cluster topologically in a human PPI network with the known pigment regulator Endothelin receptor type B (EDNRB). Validation studies reveal that these genes impact pigment production and EDNRB signaling in pigmented melanoma cells (MNT-1) and normal melanocytes. Conclusions We present an approach that identifies novel components of well-characterized biological pathways from functional genomics datasets that could not have been identified by existing statistical and computational approaches. PMID:20550706

Surface functionalization of bioactive glasses with natural molecules of biological significance, part II: Grafting of polyphenols extracted from grape skin

NASA Astrophysics Data System (ADS)

Zhang, Xin; Ferraris, Sara; Prenesti, Enrico; Verné, Enrica

2013-12-01

Polyphenols, as one of the most important family of phytochemicals protective substances from grape fruit, possess various biological activities and health-promoting benefits, for example: inhibition of some degenerative diseases, cardiovascular diseases and certain types of cancers, reduction of plasma oxidative stress and slowing aging. The combination of polyphenols and biomaterials may have good potential to reach good bioavailability and controlled release, as well as to give biological signaling properties to the biomaterial surfaces. In this research, conventional solvent extraction was developed for obtaining polyphenols from dry grape skins. The Folin&Ciocalteu method was used to determine the amount of total polyphenols in the extracts. Surface functionalization of two bioactive glasses (SCNA and CEL2) was performed by grafting the extracted polyphenols on their surfaces. The effectiveness of the functionalization was tested by UV spectroscopy, which analyzes the amount of polyphenols in the uptake solution (before and after functionalization) and on solid samples, and XPS, which analyzes the presence of phenols on the material surface.

Novel aspects of endometrial function: a biological sensor of embryo quality and driver of pregnancy success.

PubMed

Sandra, Olivier; Mansouri-Attia, Nadéra; Lea, Richard G

2011-01-01

Successful pregnancy depends on complex biological processes that are regulated temporally and spatially throughout gestation. The molecular basis of these processes have been examined in relation to gamete quality, early blastocyst development and placental function, and data have been generated showing perturbations of these developmental stages by environmental insults or embryo biotechnologies. The developmental period falling between the entry of the blastocyst into the uterine cavity to implantation has also been examined in terms of the biological function of the endometrium. Indeed several mechanisms underlying uterine receptivity, controlled by maternal factors, and the maternal recognition of pregnancy, requiring conceptus-produced signals, have been clarified. Nevertheless, recent data based on experimental perturbations have unveiled unexpected biological properties of the endometrium (sensor/driver) that make this tissue a dynamic and reactive entity. Persistent or transient modifications in organisation and functionality of the endometrium can dramatically affect pre-implantation embryo trajectory through epigenetic alterations with lasting consequences on later stages of pregnancy, including placentation, fetal development, pregnancy outcome and post-natal health. Developing diagnostic and prognostic tools based on endometrial factors may enable the assessment of maternal reproductive capacity and/or the developmental potential of the embryo, particularly when assisted reproductive technologies are applied.

Assessment of Diverse Biological Indicators in Gulf War Illness: Are They Replicable Are They Related

DTIC Science & Technology

2016-04-01

compared to 50 healthy veteran controls in a protocol that includes physical and neuropsychological evaluations, neuroimaging (MRI, fMRI, DTI), adrenal...SUBJECT TERMS Gulf War illness, neuroimaging, neuropsychological testing, immune function, hypothalamic-pituitary-adrenal testing 16. SECURITY... neuropsychological evaluations, assessment of hypothalamic-pituitary-adrenal function, standard clinical diagnostic laboratory tests, and research

Paternal Correlates of Cognitive and Behavioral Functioning in Children with Myelomeningocele

ERIC Educational Resources Information Center

Wohlfeiler, Melissa M.; Macias, Michelle M.; Saylor, Conway F.

2008-01-01

This study examined paternal correlates of the cognitive and behavioral functioning of children with myelomeningocele, when controlling for maternal and biological/child correlates as possible sources of variance. Participants were 48 parent dyads of children with myelomeningocele (21 males, 27 females) between the ages of 4 and 12 years (mean 8y,…

Cellular Metabolic and Autophagic Pathways: Traffic Control by Redox Signaling

PubMed Central

Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua

2013-01-01

It has been established that the key metabolic pathways of glycolysis and oxidative phosphorylation are intimately related to redox biology through control of cell signaling. Under physiological conditions glucose metabolism is linked to control of the NADH/NAD redox couple, as well as providing the major reductant, NADPH, for thiol-dependent antioxidant defenses. Retrograde signaling from the mitochondrion to the nucleus or cytosol controls cell growth and differentiation. Under pathological conditions mitochondria are targets for reactive oxygen and nitrogen species and are critical in controlling apoptotic cell death. At the interface of these metabolic pathways, the autophagy-lysosomal pathway functions to maintain mitochondrial quality, and generally serves an important cytoprotective function. In this review we will discuss the autophagic response to reactive oxygen and nitrogen species that are generated from perturbations of cellular glucose metabolism and bioenergetic function. PMID:23702245

Top-down causation by information control: from a philosophical problem to a scientific research programme

PubMed Central

Auletta, G; Ellis, G.F.R; Jaeger, L

2008-01-01

It has been claimed that different types of causes must be considered in biological systems, including top-down as well as same-level and bottom-up causation, thus enabling the top levels to be causally efficacious in their own right. To clarify this issue, the important distinctions between information and signs are introduced here and the concepts of information control and functional equivalence classes in those systems are rigorously defined and used to characterize when top-down causation by feedback control happens, in a way that is testable. The causally significant elements we consider are equivalence classes of lower level processes, realized in biological systems through different operations having the same outcome within the context of information control and networks. PMID:18319208

Graphene-polymer hybrid nanostructure-based bioenergy storage device for real-time control of biological motor activity.

PubMed

Byun, Kyung-Eun; Choi, Dong Shin; Kim, Eunji; Seo, David H; Yang, Heejun; Seo, Sunae; Hong, Seunghun

2011-11-22

We report a graphene-polymer hybrid nanostructure-based bioenergy storage device to turn on and off biomotor activity in real-time. In this strategy, graphene was functionalized with amine groups and utilized as a transparent electrode supporting the motility of biomotors. Conducting polymer patterns doped with adenosine triphosphate (ATP) were fabricated on the graphene and utilized for the fast release of ATP by electrical stimuli through the graphene. The controlled release of biomotor fuel, ATP, allowed us to control the actin filament transportation propelled by the biomotor in real-time. This strategy should enable the integrated nanodevices for the real-time control of biological motors, which can be a significant stepping stone toward hybrid nanomechanical systems based on motor proteins. © 2011 American Chemical Society

Molecular biomimetics: GEPI-based biological routes to technology.

PubMed

Tamerler, Candan; Khatayevich, Dmitriy; Gungormus, Mustafa; Kacar, Turgay; Oren, E Emre; Hnilova, Marketa; Sarikaya, Mehmet

2010-01-01

In nature, the viability of biological systems is sustained via specific interactions among the tens of thousands of proteins, the major building blocks of organisms from the simplest single-celled to the most complex multicellular species. Biomolecule-material interaction is accomplished with molecular specificity and efficiency leading to the formation of controlled structures and functions at all scales of dimensional hierarchy. Through evolution, Mother Nature developed molecular recognition by successive cycles of mutation and selection. Molecular specificity of probe-target interactions, e.g., ligand-receptor, antigen-antibody, is always based on specific peptide molecular recognition. Using biology as a guide, we can now understand, engineer, and control peptide-material interactions and exploit them as a new design tool for novel materials and systems. We adapted the protocols of combinatorially designed peptide libraries, via both cell surface or phage display methods; using these we select short peptides with specificity to a variety of practical materials. These genetically engineered peptides for inorganics (GEPI) are then studied experimentally to establish their binding kinetics and surface stability. The bound peptide structure and conformations are interrogated both experimentally and via modeling, and self-assembly characteristics are tested via atomic force microscopy. We further engineer the peptide binding and assembly characteristics using a computational biomimetics approach where bioinformatics based peptide-sequence similarity analysis is developed to design higher generation function-specific peptides. The molecular biomimetic approach opens up new avenues for the design and utilization of multifunctional molecular systems in a wide-range of applications from tissue engineering, disease diagnostics, and therapeutics to various areas of nanotechnology where integration is required among inorganic, organic and biological materials. Here, we describe lessons from biology with examples of protein-mediated functional biological materials, explain how novel peptides can be designed with specific affinity to inorganic solids using evolutionary engineering approaches, give examples of their potential utilizations in technology and medicine, and, finally, provide a summary of challenges and future prospects. (c) 2010 Wiley Periodicals, Inc.

Reproductive hormones and metabolic syndrome in 24 testicular cancer survivors and their biological brothers.

PubMed

Bandak, M; Jørgensen, N; Juul, A; Lauritsen, J; Kier, M G G; Mortensen, M S; Oturai, P S; Mortensen, J; Hojman, P; Helge, J W; Daugaard, G

2017-07-01

Testicular cancer survivors have impaired gonadal function and increased risk of metabolic syndrome when compared to healthy controls. However, because of the fetal etiology of testicular cancer, familial unrelated healthy men might not be an optimal control group. The objective of this study was to clarify if testicular cancer survivors have impaired gonadal function and increased risk of metabolic syndrome when compared to their biological brothers. A cross-sectional study of testicular cancer survivors (ClinicalTrials.gov number, NCT02240966) was conducted between 2014 and 2016. Of 158 testicular cancer survivors included, 24 had a biological brother who accepted to participate in the study. Serum levels of reproductive hormones and prevalence of metabolic syndrome according to International Diabetes Federation Criteria and National Cholesterol Education Program (Adult Treatment Panel III) criteria comprised the main outcome measures of the study. Median age was similar in testicular cancer survivors and their biological brothers [44 years (IQR 39-50) vs. 46 (40-53) years respectively (p = 0.1)]. In testicular cancer survivors, follow-up since treatment was 12 years (7-19). Serum levels of luteinizing hormone and follicle-stimulating hormone were elevated (p ≤ 0.001), while total testosterone, free testosterone, inhibin B and anti-Müllerian hormone were lower (p ≤ 0.001) in testicular cancer survivors than in their biological brothers. The prevalence of metabolic syndrome was similar and apart from HDL-cholesterol, which was lower in testicular cancer survivors (p = 0.01); there were no differences in the individual components of the metabolic syndrome between testicular cancer survivors and their brothers. In conclusion, gonadal function was impaired in testicular cancer survivors, while we did not detect any difference in the prevalence of metabolic syndrome between testicular cancer survivors and their biological brothers. © 2017 American Society of Andrology and European Academy of Andrology.

Locomotor Sub-functions for Control of Assistive Wearable Robots.

PubMed

Sharbafi, Maziar A; Seyfarth, Andre; Zhao, Guoping

2017-01-01

A primary goal of comparative biomechanics is to understand the fundamental physics of locomotion within an evolutionary context. Such an understanding of legged locomotion results in a transition from copying nature to borrowing strategies for interacting with the physical world regarding design and control of bio-inspired legged robots or robotic assistive devices. Inspired from nature, legged locomotion can be composed of three locomotor sub-functions, which are intrinsically interrelated: Stance : redirecting the center of mass by exerting forces on the ground. Swing : cycling the legs between ground contacts. Balance : maintaining body posture. With these three sub-functions, one can understand, design and control legged locomotory systems with formulating them in simpler separated tasks. Coordination between locomotor sub-functions in a harmonized manner appears then as an additional problem when considering legged locomotion. However, biological locomotion shows that appropriate design and control of each sub-function simplifies coordination. It means that only limited exchange of sensory information between the different locomotor sub-function controllers is required enabling the envisioned modular architecture of the locomotion control system. In this paper, we present different studies on implementing different locomotor sub-function controllers on models, robots, and an exoskeleton in addition to demonstrating their abilities in explaining humans' control strategies.

Locomotor Sub-functions for Control of Assistive Wearable Robots

PubMed Central

Sharbafi, Maziar A.; Seyfarth, Andre; Zhao, Guoping

2017-01-01

A primary goal of comparative biomechanics is to understand the fundamental physics of locomotion within an evolutionary context. Such an understanding of legged locomotion results in a transition from copying nature to borrowing strategies for interacting with the physical world regarding design and control of bio-inspired legged robots or robotic assistive devices. Inspired from nature, legged locomotion can be composed of three locomotor sub-functions, which are intrinsically interrelated: Stance: redirecting the center of mass by exerting forces on the ground. Swing: cycling the legs between ground contacts. Balance: maintaining body posture. With these three sub-functions, one can understand, design and control legged locomotory systems with formulating them in simpler separated tasks. Coordination between locomotor sub-functions in a harmonized manner appears then as an additional problem when considering legged locomotion. However, biological locomotion shows that appropriate design and control of each sub-function simplifies coordination. It means that only limited exchange of sensory information between the different locomotor sub-function controllers is required enabling the envisioned modular architecture of the locomotion control system. In this paper, we present different studies on implementing different locomotor sub-function controllers on models, robots, and an exoskeleton in addition to demonstrating their abilities in explaining humans' control strategies. PMID:28928650

Nanopipettes as Monitoring Probes for the Single Living Cell: State of the Art and Future Directions in Molecular Biology.

PubMed

Bulbul, Gonca; Chaves, Gepoliano; Olivier, Joseph; Ozel, Rifat Emrah; Pourmand, Nader

2018-06-06

Examining the behavior of a single cell within its natural environment is valuable for understanding both the biological processes that control the function of cells and how injury or disease lead to pathological change of their function. Single-cell analysis can reveal information regarding the causes of genetic changes, and it can contribute to studies on the molecular basis of cell transformation and proliferation. By contrast, whole tissue biopsies can only yield information on a statistical average of several processes occurring in a population of different cells. Electrowetting within a nanopipette provides a nanobiopsy platform for the extraction of cellular material from single living cells. Additionally, functionalized nanopipette sensing probes can differentiate analytes based on their size, shape or charge density, making the technology uniquely suited to sensing changes in single-cell dynamics. In this review, we highlight the potential of nanopipette technology as a non-destructive analytical tool to monitor single living cells, with particular attention to integration into applications in molecular biology.

The Mediator Complex and Lipid Metabolism.

PubMed

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

2013-03-01

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

Mammalian Synthetic Biology: Engineering Biological Systems.

PubMed

Black, Joshua B; Perez-Pinera, Pablo; Gersbach, Charles A

2017-06-21

The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution. These tools have been critical for the expansion of synthetic biology techniques from prokaryotic and lower eukaryotic hosts to mammalian systems. Recent progress in the development of genome and epigenome editing tools and in the engineering of designer cells with programmable genetic circuits is expanding approaches to prevent, diagnose, and treat disease and to establish personalized theranostic strategies for next-generation medicines. This review summarizes the development of these enabling technologies and their application to transforming mammalian synthetic biology into a distinct field in research and medicine.

Ion transport controlled by nanoparticle-functionalized membranes.

PubMed

Barry, Edward; McBride, Sean P; Jaeger, Heinrich M; Lin, Xiao-Min

2014-12-17

From proton exchange membranes in fuel cells to ion channels in biological membranes, the well-specified control of ionic interactions in confined geometries profoundly influences the transport and selectivity of porous materials. Here we outline a versatile new approach to control a membrane's electrostatic interactions with ions by depositing ligand-coated nanoparticles around the pore entrances. Leveraging the flexibility and control by which ligated nanoparticles can be synthesized, we demonstrate how ligand terminal groups such as methyl, carboxyl and amine can be used to tune the membrane charge density and control ion transport. Further functionality, exploiting the ligands as binding sites, is demonstrated for sulfonate groups resulting in an enhancement of the membrane charge density. We then extend these results to smaller dimensions by systematically varying the underlying pore diameter. As a whole, these results outline a previously unexplored method for the nanoparticle functionalization of membranes using ligated nanoparticles to control ion transport.

Ion transport controlled by nanoparticle-functionalized membranes

NASA Astrophysics Data System (ADS)

Barry, Edward; McBride, Sean P.; Jaeger, Heinrich M.; Lin, Xiao-Min

2014-12-01

From proton exchange membranes in fuel cells to ion channels in biological membranes, the well-specified control of ionic interactions in confined geometries profoundly influences the transport and selectivity of porous materials. Here we outline a versatile new approach to control a membrane’s electrostatic interactions with ions by depositing ligand-coated nanoparticles around the pore entrances. Leveraging the flexibility and control by which ligated nanoparticles can be synthesized, we demonstrate how ligand terminal groups such as methyl, carboxyl and amine can be used to tune the membrane charge density and control ion transport. Further functionality, exploiting the ligands as binding sites, is demonstrated for sulfonate groups resulting in an enhancement of the membrane charge density. We then extend these results to smaller dimensions by systematically varying the underlying pore diameter. As a whole, these results outline a previously unexplored method for the nanoparticle functionalization of membranes using ligated nanoparticles to control ion transport.

Centrin 3 is an inhibitor of centrosomal Mps1 and antagonizes centrin 2 function

PubMed Central

Sawant, Dwitiya B.; Majumder, Shubhra; Perkins, Jennifer L.; Yang, Ching-Hui; Eyers, Patrick A.; Fisk, Harold A.

2015-01-01

Centrins are a family of small, calcium-binding proteins with diverse cellular functions that play an important role in centrosome biology. We previously identified centrin 2 and centrin 3 (Cetn2 and Cetn3) as substrates of the protein kinase Mps1. However, although Mps1 phosphorylation sites control the function of Cetn2 in centriole assembly and promote centriole overproduction, Cetn2 and Cetn3 are not functionally interchangeable, and we show here that Cetn3 is both a biochemical inhibitor of Mps1 catalytic activity and a biological inhibitor of centrosome duplication. In vitro, Cetn3 inhibits Mps1 autophosphorylation at Thr-676, a known site of T-loop autoactivation, and interferes with Mps1-dependent phosphorylation of Cetn2. The cellular overexpression of Cetn3 attenuates the incorporation of Cetn2 into centrioles and centrosome reduplication, whereas depletion of Cetn3 generates extra centrioles. Finally, overexpression of Cetn3 reduces Mps1 Thr-676 phosphorylation at centrosomes, and mimicking Mps1-dependent phosphorylation of Cetn2 bypasses the inhibitory effect of Cetn3, suggesting that the biological effects of Cetn3 are due to the inhibition of Mps1 function at centrosomes. PMID:26354417

Cooperativity to increase Turing pattern space for synthetic biology.

PubMed

Diambra, Luis; Senthivel, Vivek Raj; Menendez, Diego Barcena; Isalan, Mark

2015-02-20

It is hard to bridge the gap between mathematical formulations and biological implementations of Turing patterns, yet this is necessary for both understanding and engineering these networks with synthetic biology approaches. Here, we model a reaction-diffusion system with two morphogens in a monostable regime, inspired by components that we recently described in a synthetic biology study in mammalian cells.1 The model employs a single promoter to express both the activator and inhibitor genes and produces Turing patterns over large regions of parameter space, using biologically interpretable Hill function reactions. We applied a stability analysis and identified rules for choosing biologically tunable parameter relationships to increase the likelihood of successful patterning. We show how to control Turing pattern sizes and time evolution by manipulating the values for production and degradation relationships. More importantly, our analysis predicts that steep dose-response functions arising from cooperativity are mandatory for Turing patterns. Greater steepness increases parameter space and even reduces the requirement for differential diffusion between activator and inhibitor. These results demonstrate some of the limitations of linear scenarios for reaction-diffusion systems and will help to guide projects to engineer synthetic Turing patterns.

The role of symmetry in the regulation of brain dynamics

NASA Astrophysics Data System (ADS)

Tang, Evelyn; Giusti, Chad; Cieslak, Matthew; Grafton, Scott; Bassett, Danielle

Synchronous neural processes regulate a wide range of behaviors from attention to learning. Yet structural constraints on these processes are far from understood. We draw on new theoretical links between structural symmetries and the control of synchronous function, to offer a reconceptualization of the relationships between brain structure and function in human and non-human primates. By classifying 3-node motifs in macaque connectivity data, we find the most prevalent motifs can theoretically ensure a diversity of function including strict synchrony as well as control to arbitrary states. The least prevalent motifs are theoretically controllable to arbitrary states, which may not be desirable in a biological system. In humans, regions with high topological similarity of connections (a continuous notion related to symmetry) are most commonly found in fronto-parietal systems, which may account for their critical role in cognitive control. Collectively, our work underscores the role of symmetry and topological similarity in regulating dynamics of brain function.

Controlling automatic imitative tendencies: interactions between mirror neuron and cognitive control systems.

PubMed

Cross, Katy A; Torrisi, Salvatore; Reynolds Losin, Elizabeth A; Iacoboni, Marco

2013-12-01

Humans have an automatic tendency to imitate others. Although several regions commonly observed in social tasks have been shown to be involved in imitation control, there is little work exploring how these regions interact with one another. We used fMRI and dynamic causal modeling to identify imitation-specific control mechanisms and examine functional interactions between regions. Participants performed a pre-specified action (lifting their index or middle finger) in response to videos depicting the same two actions (biological cues) or dots moving with similar trajectories (non-biological cues). On congruent trials, the stimulus and response were similar (e.g. index finger response to index finger or left side dot stimulus), while on incongruent trials the stimulus and response were dissimilar (e.g. index finger response to middle finger or right side dot stimulus). Reaction times were slower on incongruent compared to congruent trials for both biological and non-biological stimuli, replicating previous findings that suggest the automatic imitative or spatially compatible (congruent) response must be controlled on incongruent trials. Neural correlates of the congruency effects were different depending on the cue type. The medial prefrontal cortex, anterior cingulate, inferior frontal gyrus pars opercularis (IFGpo) and the left anterior insula were involved specifically in controlling imitation. In addition, the IFGpo was also more active for biological compared to non-biological stimuli, suggesting that the region represents the frontal node of the human mirror neuron system (MNS). Effective connectivity analysis exploring the interactions between these regions, suggests a role for the mPFC and ACC in imitative conflict detection and the anterior insula in conflict resolution processes, which may occur through interactions with the frontal node of the MNS. We suggest an extension of the previous models of imitation control involving interactions between imitation-specific and general cognitive control mechanisms. © 2013.

Endocytosis and Signaling during Development

PubMed Central

Bökel, Christian

2014-01-01

The development of multicellular organisms relies on an intricate choreography of intercellular communication events that pattern the embryo and coordinate the formation of tissues and organs. It is therefore not surprising that developmental biology, especially using genetic model organisms, has contributed significantly to the discovery and functional dissection of the associated signal-transduction cascades. At the same time, biophysical, biochemical, and cell biological approaches have provided us with insights into the underlying cell biological machinery. Here we focus on how endocytic trafficking of signaling components (e.g., ligands or receptors) controls the generation, propagation, modulation, reception, and interpretation of developmental signals. A comprehensive enumeration of the links between endocytosis and signal transduction would exceed the limits of this review. We will instead use examples from different developmental pathways to conceptually illustrate the various functions provided by endocytic processes during key steps of intercellular signaling. PMID:24591521

Hormonal control of implantation.

PubMed

Sandra, Olivier

2016-06-01

In mammals, implantation represents a key step of pregnancy and its progression conditions not only the success of pregnancy but health of the offspring. Implantation requires a complex and specific uterine tissue, the endometrium, whose biological functions are tightly regulated by numerous signals, including steroids and polypeptide hormones. Endometrial tissue is endowed with dynamic properties that associate its ability to control the developmental trajectory of the embryo (driver property) and its ability to react to embryos displaying distinct capacities to develop to term (sensor property). Since dynamical properties of the endometrium can be affected by pre- and post-conceptional environment, determining how maternal hormonal signals and their biological actions are affected by environmental factors (e.g. nutrition, stress, infections) is mandatory to reduce or even to prevent their detrimental effects on endometrial physiology in order to preserve the optimal functionality of this tissue. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Induced Fit in Protein Multimerization: The HFBI Case

PubMed Central

Riccardi, Laura

2016-01-01

Hydrophobins, produced by filamentous fungi, are small amphipathic proteins whose biological functions rely on their unique surface-activity properties. Understanding the mechanistic details of the multimerization process is of primary importance to clarify the interfacial activity of hydrophobins. We used free energy calculations to study the role of a flexible β-hairpin in the multimerization process in hydrophobin II from Trichoderma reesei (HFBI). We characterized how the displacement of this β-hairpin controls the stability of the monomers/dimers/tetramers in solution. The regulation of the oligomerization equilibrium of HFBI will necessarily affect its interfacial properties, fundamental for its biological function and for technological applications. Moreover, we propose possible routes for the multimerization process of HFBI in solution. This is the first case where a mechanism by which a flexible loop flanking a rigid patch controls the protein-protein binding equilibrium, already known for proteins with charged binding hot-spots, is described within a hydrophobic patch. PMID:27832079

Tiling solutions for optimal biological sensing

NASA Astrophysics Data System (ADS)

Walczak, Aleksandra M.

2015-10-01

Biological systems, from cells to organisms, must respond to the ever-changing environment in order to survive and function. This is not a simple task given the often random nature of the signals they receive, as well as the intrinsically stochastic, many-body and often self-organized nature of the processes that control their sensing and response and limited resources. Despite a wide range of scales and functions that can be observed in the living world, some common principles that govern the behavior of biological systems emerge. Here I review two examples of very different biological problems: information transmission in gene regulatory networks and diversity of adaptive immune receptor repertoires that protect us from pathogens. I discuss the trade-offs that physical laws impose on these systems and show that the optimal designs of both immune repertoires and gene regulatory networks display similar discrete tiling structures. These solutions rely on locally non-overlapping placements of the responding elements (genes and receptors) that, overall, cover space nearly uniformly.

Emergence of biological organization through thermodynamic inversion.

PubMed

Kompanichenko, Vladimir

2014-01-01

Biological organization arises under thermodynamic inversion in prebiotic systems that provide the prevalence of free energy and information contribution over the entropy contribution. The inversion might occur under specific far-from-equilibrium conditions in prebiotic systems oscillating around the bifurcation point. At the inversion moment, (physical) information characteristic of non-biological systems acquires the new features: functionality, purposefulness, and control over the life processes, which transform it into biological information. Random sequences of amino acids and nucleotides, spontaneously synthesized in the prebiotic microsystem, in the primary living unit (probiont) re-assemble into functional sequences, involved into bioinformation circulation through nucleoprotein interaction, resulted in the genetic code emergence. According to the proposed concept, oscillating three-dimensional prebiotic microsystems transformed into probionts in the changeable hydrothermal medium of the early Earth. The inversion concept states that spontaneous (accidental, random) transformations in prebiotic systems cannot produce life; it is only non-spontaneous (perspective, purposeful) transformations, which are the result of thermodynamic inversion, that lead to the negentropy conversion of prebiotic systems into initial living units.

Pushing the lipid envelope: using bio-inspired nanocomposites to understand and exploit lipid membrane limitations

NASA Astrophysics Data System (ADS)

Montano, Gabriel

Lipids serve as the organizing matrix material for biological membranes, the site of interaction of cells with the external environment. . As such, lipids play a critical role in structure/function relationships of an extraordinary number of critical biological processes. In this talk, we will look at bio-inspired membrane assemblies to better understand the roles of lipids in biological systems as well as attempt to generate materials that can mimic and potentially advance upon biological membrane processes. First, we will investigate the response of lipids to adverse conditions. In particular, I will present data that demonstrates the response of lipids to harsh conditions and how such responses can be exploited to generate nanocomposite rearrangements. I will also show the effect of adding the endotoxin lipopolysaccharide (LPS) to lipid bilayer assemblies and describe implications on our understanding of LPS organization in biological systems as well as describe induced lipid modifications that can be exploited to organize membrane composites with precise, two-dimensional geometric control. Lastly, I will describe the use of amphiphilic block copolymers to create membrane nanocomposites capable of mimicking biological systems. In particular, I will describe the use of our polymer-based membranes in creating artificial photosynthetic assemblies that rival biological systems in function in a more flexible, dynamic matrix.

RNA and RNP as Building Blocks for Nanotechnology and Synthetic Biology.

PubMed

Ohno, Hirohisa; Saito, Hirohide

2016-01-01

Recent technologies that aimed to elucidate cellular function have revealed essential roles for RNA molecules in living systems. Our knowledge concerning functional and structural information of naturally occurring RNA and RNA-protein (RNP) complexes is increasing rapidly. RNA and RNP interaction motifs are structural units that function as building blocks to constitute variety of complex structures. RNA-central synthetic biology and nanotechnology are constructive approaches that employ the accumulated information and build synthetic RNA (RNP)-based circuits and nanostructures. Here, we describe how to design and construct synthetic RNA (RNP)-based devices and structures at the nanometer-scale for biological and future therapeutic applications. RNA/RNP nanostructures can also be utilized as the molecular scaffold to control the localization or interactions of target molecule(s). Moreover, RNA motifs recognized by RNA-binding proteins can be applied to make protein-responsive translational "switches" that can turn gene expression "on" or "off" depending on the intracellular environment. This "synthetic RNA and RNP world" will expand tools for nanotechnology and synthetic biology. In addition, these reconstructive approaches would lead to a greater understanding of building principle in naturally occurring RNA/RNP molecules and systems. Copyright © 2016 Elsevier Inc. All rights reserved.

From Discovery to Function: The Expanding Roles of Long NonCoding RNAs in Physiology and Disease

PubMed Central

Sun, Miao

2015-01-01

Long noncoding RNAs (lncRNAs) are a relatively poorly understood class of RNAs with little or no coding capacity transcribed from a set of incompletely annotated genes. They have received considerable attention in the past few years and are emerging as potentially important players in biological regulation. Here we discuss the evolving understanding of this new class of molecular regulators that has emerged from ongoing research, which continues to expand our databases of annotated lncRNAs and provide new insights into their physical properties, molecular mechanisms of action, and biological functions. We outline the current strategies and approaches that have been employed to identify and characterize lncRNAs, which have been instrumental in revealing their multifaceted roles ranging from cis- to trans-regulation of gene expression and from epigenetic modulation in the nucleus to posttranscriptional control in the cytoplasm. In addition, we highlight the molecular and biological functions of some of the best characterized lncRNAs in physiology and disease, especially those relevant to endocrinology, reproduction, metabolism, immunology, neurobiology, muscle biology, and cancer. Finally, we discuss the tremendous diagnostic and therapeutic potential of lncRNAs in cancer and other diseases. PMID:25426780

From discovery to function: the expanding roles of long noncoding RNAs in physiology and disease.

PubMed

Sun, Miao; Kraus, W Lee

2015-02-01

Long noncoding RNAs (lncRNAs) are a relatively poorly understood class of RNAs with little or no coding capacity transcribed from a set of incompletely annotated genes. They have received considerable attention in the past few years and are emerging as potentially important players in biological regulation. Here we discuss the evolving understanding of this new class of molecular regulators that has emerged from ongoing research, which continues to expand our databases of annotated lncRNAs and provide new insights into their physical properties, molecular mechanisms of action, and biological functions. We outline the current strategies and approaches that have been employed to identify and characterize lncRNAs, which have been instrumental in revealing their multifaceted roles ranging from cis- to trans-regulation of gene expression and from epigenetic modulation in the nucleus to posttranscriptional control in the cytoplasm. In addition, we highlight the molecular and biological functions of some of the best characterized lncRNAs in physiology and disease, especially those relevant to endocrinology, reproduction, metabolism, immunology, neurobiology, muscle biology, and cancer. Finally, we discuss the tremendous diagnostic and therapeutic potential of lncRNAs in cancer and other diseases.

Mammalian synthetic biology for studying the cell

PubMed Central

Mathur, Melina; Xiang, Joy S.

2017-01-01

Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. PMID:27932576

The Arabidopsis domain of unknown function 1218 (DUF1218) containing proteins, MODIFYING WALL LIGNIN-1 and 2 (At1g31720/MWL-1 and At4g19370/MWL-2) function redundantly to alter secondary cell wall lignin content

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

Mewalal, Ritesh; Mizrachi, Eshchar; Coetzee, Berdine

DUF1218 is a land plant-specific innovation and has previously been shown to be associated with cell wall biology, vasculature patterning and abiotic/biotic stress response. The Arabidopsis genome encodes 15 members, two of which (At1g31720 and At4g27435) are preferentially expressed in the secondary cell wall depositing inflorescence stems. To further our understanding of the roles of DUF1218-containing proteins in secondary cell wall biology, we functionally characterized At1g31720 (herein referred to as MODIFYING WALL LIGNIN-1 or MWL-1). Since related gene family members may contribute to functional redundancy, we also characterized At4g19370 ( MWL-2), the most closely related gene to MWL-1 in themore » protein family. Subcellular localization revealed that both Arabidopsis proteins are targeted to the cell periphery. The single T-DNA knockout lines, mwl-1 and mwl-2, and independent overexpression lines showed no significant differences in plant growth or changes in total lignin content relative to wild-type (WT) control plants. However, the double homozygous mutant, mwl-1/ mwl-2, had smaller rosettes with a significant decrease in rosette fresh weight and stem height relative to the WT control at four weeks and six weeks, respectively. Moreover, mwl-1/ mwl-2 showed a significant reduction in total lignin content (by ca. 11% relative to WT) and an increase in syringyl/guaiacyl (S/G) monomer ratio relative to the control plants. Lastly, our study has identified two additional members of the DUF1218 family in Arabidopsis as novel contributors to secondary cell wall biology, specifically lignin biosynthesis, and these proteins appear to function redundantly.« less

The Arabidopsis domain of unknown function 1218 (DUF1218) containing proteins, MODIFYING WALL LIGNIN-1 and 2 (At1g31720/MWL-1 and At4g19370/MWL-2) function redundantly to alter secondary cell wall lignin content

DOE PAGES

Mewalal, Ritesh; Mizrachi, Eshchar; Coetzee, Berdine; ...

2016-03-01

DUF1218 is a land plant-specific innovation and has previously been shown to be associated with cell wall biology, vasculature patterning and abiotic/biotic stress response. The Arabidopsis genome encodes 15 members, two of which (At1g31720 and At4g27435) are preferentially expressed in the secondary cell wall depositing inflorescence stems. To further our understanding of the roles of DUF1218-containing proteins in secondary cell wall biology, we functionally characterized At1g31720 (herein referred to as MODIFYING WALL LIGNIN-1 or MWL-1). Since related gene family members may contribute to functional redundancy, we also characterized At4g19370 ( MWL-2), the most closely related gene to MWL-1 in themore » protein family. Subcellular localization revealed that both Arabidopsis proteins are targeted to the cell periphery. The single T-DNA knockout lines, mwl-1 and mwl-2, and independent overexpression lines showed no significant differences in plant growth or changes in total lignin content relative to wild-type (WT) control plants. However, the double homozygous mutant, mwl-1/ mwl-2, had smaller rosettes with a significant decrease in rosette fresh weight and stem height relative to the WT control at four weeks and six weeks, respectively. Moreover, mwl-1/ mwl-2 showed a significant reduction in total lignin content (by ca. 11% relative to WT) and an increase in syringyl/guaiacyl (S/G) monomer ratio relative to the control plants. Lastly, our study has identified two additional members of the DUF1218 family in Arabidopsis as novel contributors to secondary cell wall biology, specifically lignin biosynthesis, and these proteins appear to function redundantly.« less

[The biological reaction of inflammation, methylglyoxal of blood plasma, functional and structural alterations in elastic type arteries at the early stage of hypertension disease].

PubMed

Titov, V N; Dmitriev, V A; Oshchepkov, E V; Balakhonova, T V; Tripoten', M I; Shiriaeva, Iu K

2012-08-01

The article deals with studying of the relationship between biologic reaction of inflammation with glycosylation reaction and content of methylglyoxal in blood serum. The positive correlation between pulse wave velocity and content of methylglyoxal, C-reactive protein in intercellular medium and malleolar brachial index value was established. This data matches the experimental results concerning involvement of biological reaction of inflammation into structural changes of elastic type arteries under hypertension disease, formation of arteries' rigidity and increase of pulse wave velocity. The arterial blood pressure is a biological reaction of hydrodynamic pressure which is used in vivo by several biological functions: biological function of homeostasis, function of endoecology, biological function of adaptation and function of locomotion. The biological reaction of hydrodynamic (hydraulic) pressure is a mode of compensation of derangement of several biological functions which results in the very high rate of hypertension disease in population. As a matter of fact, hypertension disease is a syndrome of lingering pathological compensation by higher arterial blood pressure of the biological functions derangements occurring in the distal section at the level of paracrine cenoses of cells. The arterial blood pressure is a kind of in vivo integral indicator of deranged metabolism. The essential hypertension disease pathogenically is a result of the derangement of three biological functions: biological function of homeostasis, biological function of trophology - nutrition (biological reaction of external feeding - exotrophia) and biological function of endoecology. In case of "littering" of intercellular medium in vivo with nonspecific endogenic flogogens a phylogenetically earlier activation of biological reactions of excretion, inflammation and hydrodynamic arterial blood pressure occur. In case of derangement of biological function of homeostasis, decreasing of perfusion even in single paracrine cenoses and derangement of biological function of endoecology ("purity" of intercellular medium) the only response always will be the increase of arterial blood pressure.

Understanding perceptions of stuttering among school-based speech-language pathologists: an application of attribution theory.

PubMed

Boyle, Michael P

2014-01-01

The purpose of this study was to investigate whether attribution theory could explain speech-language pathologists (SLPs) perceptions of children with communication disorders such as stuttering. Specifically, it was determined whether perceptions of onset and offset controllability, as well as biological and non-biological attributions for communication disorders were related to willingness to help, sympathy, and anger toward children with these disorders. It was also of interest to determine if blame for stuttering was related to perceived controllability of stuttering and negative attitudes toward people who stutter (PWS). A survey was developed to measure perceived onset and offset controllability, biological and non-biological attributions, willingness to help, sympathy, and anger toward middle school children with developmental stuttering, functional articulation disorders, and cerebral palsy. In addition, a scale was developed to measure blame and negative attitudes toward PWS in general. Surveys were mailed to 1000 school-based SLPs. Data from 330 participants were analyzed. Supporting the hypotheses of attribution theory, higher perceived onset and offset controllability of the disorder was linked to less willingness to help, lower sympathy, and more anger across conditions. Increased biological attributions were associated with more reported sympathy. Increased blame for stuttering was linked to higher perceived controllability of stuttering, more dislike of PWS, and more agreement with negative stereotypes about PWS. Educating SLPs about the variable loss of control inherent in stuttering could improve attitudes and increase understanding of PWS. Reductions in blame may facilitate feelings of sympathy and empathy for PWS and reduce environmental barriers for clients. Learning outcomes Readers should be able to: (1) identify the main principles of Weiner's attribution theory (2) identify common negative perceptions of people who stutter (3) describe how disorders of stuttering, articulation disorders, and cerebral palsy are differentiated in terms of perceived onset and offset controllability, and biological and non-biological attributions (4) describe relationships between perceived onset and offset controllability of disorders and sympathy, anger, and willingness to help. Copyright © 2014 Elsevier Inc. All rights reserved.

Topological Principles of Control in Dynamical Networks

NASA Astrophysics Data System (ADS)

Kim, Jason; Pasqualetti, Fabio; Bassett, Danielle

Networked biological systems, such as the brain, feature complex patterns of interactions. To predict and correct the dynamic behavior of such systems, it is imperative to understand how the underlying topological structure affects and limits the function of the system. Here, we use network control theory to extract topological features that favor or prevent network controllability, and to understand the network-wide effect of external stimuli on large-scale brain systems. Specifically, we treat each brain region as a dynamic entity with real-valued state, and model the time evolution of all interconnected regions using linear, time-invariant dynamics. We propose a simplified feed-forward scheme where the effect of upstream regions (drivers) on the connected downstream regions (non-drivers) is characterized in closed-form. Leveraging this characterization of the simplified model, we derive topological features that predict the controllability properties of non-simplified networks. We show analytically and numerically that these predictors are accurate across a large range of parameters. Among other contributions, our analysis shows that heterogeneity in the network weights facilitate controllability, and allows us to implement targeted interventions that profoundly improve controllability. By assuming an underlying dynamical mechanism, we are able to understand the complex topology of networked biological systems in a functionally meaningful way.

Mirror me: Imitative responses in adults with autism.

PubMed

Schunke, Odette; Schöttle, Daniel; Vettorazzi, Eik; Brandt, Valerie; Kahl, Ursula; Bäumer, Tobias; Ganos, Christos; David, Nicole; Peiker, Ina; Engel, Andreas K; Brass, Marcel; Münchau, Alexander

2016-02-01

Dysfunctions of the human mirror neuron system have been postulated to underlie some deficits in autism spectrum disorders including poor imitative performance and impaired social skills. Using three reaction time experiments addressing mirror neuron system functions under simple and complex conditions, we examined 20 adult autism spectrum disorder participants and 20 healthy controls matched for age, gender and education. Participants performed simple finger-lifting movements in response to (1) biological finger and non-biological dot movement stimuli, (2) acoustic stimuli and (3) combined visual-acoustic stimuli with different contextual (compatible/incompatible) and temporal (simultaneous/asynchronous) relation. Mixed model analyses revealed slower reaction times in autism spectrum disorder. Both groups responded faster to biological compared to non-biological stimuli (Experiment 1) implying intact processing advantage for biological stimuli in autism spectrum disorder. In Experiment 3, both groups had similar 'interference effects' when stimuli were presented simultaneously. However, autism spectrum disorder participants had abnormally slow responses particularly when incompatible stimuli were presented consecutively. Our results suggest imitative control deficits rather than global imitative system impairments. © The Author(s) 2015.

Development and implementation of an expert system to improve the control of nitrification and denitrification in the Vic wastewater treatment plant.

PubMed

Ribas, F; Rodríguez-Roda, I; Serrat, J; Clara, P; Comas, J

2008-05-01

Wastewater treatment plants employ various physical, chemical and biological processes to reduce pollutants from raw wastewater. One of the most important is the biological nitrogen removal process through nitrification and denitrification steps taking place in various sections of the biological reactor. One of the most extensively used configurations to achieve the biological nitrogen removal is an activated sludge system using oxidation ditch or extended aeration. To improve nitrogen removal in the wastewater treatment plant (WWTP) of Vic (Catalonia, NE Spain), the automatic aeration control system was complemented with an Expert System to always provide the most appropriate aeration or anoxia sequence based on the values of ammonium and nitrates given by an automatic analyzer. This article illustrates the development and implementation of this knowledge-based system within the framework of a Decision Support System, which performs SCADA functions. The paper also shows that the application of the decision support system in the Vic WWTP resulted in significant improvements to the biological nitrogen removal.

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

Biological membranes

PubMed Central

Watson, Helen

2015-01-01

Biological membranes allow life as we know it to exist. They form cells and enable separation between the inside and outside of an organism, controlling by means of their selective permeability which substances enter and leave. By allowing gradients of ions to be created across them, membranes also enable living organisms to generate energy. In addition, they control the flow of messages between cells by sending, receiving and processing information in the form of chemical and electrical signals. This essay summarizes the structure and function of membranes and the proteins within them, and describes their role in trafficking and transport, and their involvement in health and disease. Techniques for studying membranes are also discussed. PMID:26504250

Linear control theory for gene network modeling.

PubMed

Shin, Yong-Jun; Bleris, Leonidas

2010-09-16

Systems biology is an interdisciplinary field that aims at understanding complex interactions in cells. Here we demonstrate that linear control theory can provide valuable insight and practical tools for the characterization of complex biological networks. We provide the foundation for such analyses through the study of several case studies including cascade and parallel forms, feedback and feedforward loops. We reproduce experimental results and provide rational analysis of the observed behavior. We demonstrate that methods such as the transfer function (frequency domain) and linear state-space (time domain) can be used to predict reliably the properties and transient behavior of complex network topologies and point to specific design strategies for synthetic networks.

Functional genomics approaches in parasitic helminths.

PubMed

Hagen, J; Lee, E F; Fairlie, W D; Kalinna, B H

2012-01-01

As research on parasitic helminths is moving into the post-genomic era, an enormous effort is directed towards deciphering gene function and to achieve gene annotation. The sequences that are available in public databases undoubtedly hold information that can be utilized for new interventions and control but the exploitation of these resources has until recently remained difficult. Only now, with the emergence of methods to genetically manipulate and transform parasitic worms will it be possible to gain a comprehensive understanding of the molecular mechanisms involved in nutrition, metabolism, developmental switches/maturation and interaction with the host immune system. This review focuses on functional genomics approaches in parasitic helminths that are currently used, to highlight potential applications of these technologies in the areas of cell biology, systems biology and immunobiology of parasitic helminths. © 2011 Blackwell Publishing Ltd.

Using multiple methods to characterize the phenotype of individuals with a family history of major depressive disorder.

PubMed

Watters, Anna J; Gotlib, Ian H; Harris, Anthony W F; Boyce, Philip M; Williams, Leanne M

2013-09-05

Unaffected relatives (URs) of individuals with major depressive disorder (MDD) are biologically more vulnerable to depression. We compare healthy URs and controls at the level of phenotype (symptoms and functioning) and endophenotype (negative emotion bias), and further investigate the interrelation between these and the contribution of environmental early life stress. URs (n=101), identified using Family History Screen interview methods and matched controls completed written and interview questions assessing symptoms of depression and anxiety, negative cognitive style, life functioning and early life stress. Biases in emotion processing were measured using a facial expression of emotion identification paradigm. Compared to controls, URs reported higher levels of depression and anxiety, a stronger negative cognitive bias, and poorer functioning and lower satisfaction with life. URs were slower to correctly identify fear and sad facial expressions. A slower response time to identify sad faces was correlated with lower quality of life in the social domain. Early life stress (ELS) did not contribute significantly to any outcome. The methodology relies on accurate reporting of participants' own psychiatric history and that of their family members. The degree of vulnerability varies among URs. A family history of depression accounts for subtle differences in symptom levels and functioning without a necessary role of ELS. A negative emotion bias in processing emotion may be one vulnerability marker for MDD. Biological markers may affect functioning measures before symptoms at the level of experience. Copyright © 2013 Elsevier B.V. All rights reserved.

Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells

NASA Astrophysics Data System (ADS)

Benoit, Danielle S. W.; Schwartz, Michael P.; Durney, Andrew R.; Anseth, Kristi S.

2008-10-01

Cell-matrix interactions have critical roles in regeneration, development and disease. The work presented here demonstrates that encapsulated human mesenchymal stem cells (hMSCs) can be induced to differentiate down osteogenic and adipogenic pathways by controlling their three-dimensional environment using tethered small-molecule chemical functional groups. Hydrogels were formed using sufficiently low concentrations of tether molecules to maintain constant physical characteristics, encapsulation of hMSCs in three dimensions prevented changes in cell morphology, and hMSCs were shown to differentiate in normal growth media, indicating that the small-molecule functional groups induced differentiation. To our knowledge, this is the first example where synthetic matrices are shown to control induction of multiple hMSC lineages purely through interactions with small-molecule chemical functional groups tethered to the hydrogel material. Strategies using simple chemistry to control complex biological processes would be particularly powerful as they could make production of therapeutic materials simpler, cheaper and more easily controlled.

ToF-SIMS Characterization of Biocompatible Silk/Polypyrrole Electromechanical Actuators

NASA Astrophysics Data System (ADS)

Bradshaw, Nathan; Severt, Sean; Wang, Zhaoying; Klemke, Carly; Larson, Jesse; Zhu, Zihua; Murphy, Amanda; Leger, Janelle

2015-03-01

Materials capable of controlled movements that can also interface with biological environments are highly sought after for biomedical devices such as valves, blood vessel sutures, cochlear implants and controlled drug release devices. Recently we have reported the synthesis of films composed of a conductive interpenetrating network of the biopolymer silk fibroin and poly(pyrrole). These silk-PPy composites function as bilayer electromechanical actuators in a biologically-relevant environment, can be actuated repeatedly, and are able to generate forces comparable with natural muscle (>0.1 MPa), making them an ideal candidate for interfacing with biological tissues. Here, time of flight secondary ion mass spectrometry was used to investigate the migration of ions in the devices during actuation. These findings will be discussed in the context of the actuation mechanism and opportunities for further improvements in device stability and performance.

Downstream of human NDR kinases: impacting on c-myc and p21 protein stability to control cell cycle progression.

PubMed

Cornils, Hauke; Kohler, Reto S; Hergovich, Alexander; Hemmings, Brian A

2011-06-15

The mammalian genome encodes four members of the NDR/LATS kinase family: NDR1 (STK38), NDR2 (STK38L), LATS1 and LATS2, which are highly conserved from yeast to man. Members of the NDR/LATS kinase family have been implicated in a variety of biological processes ranging from cell division and morphology to apoptosis and tumor suppression. In mammals, LATS1/2 function as central parts of the HIPPO tumor suppressor pathway by restricting the activity of the YAP/TAZ proto-oncogenes. Recent evidence suggested that NDR1/2 are also part of an extended HIPPO tumor suppressor pathway. Apart from functions in apoptosis signaling and tumor suppression, NDR1/2 have been implicated in controlling centrosome duplication and mitotic chromosome alignment downstream of the HIPPO kinase homologs MST1 and MST2. Significantly, we also reported recently that NDR1/2 are controlling G 1/S transition downstream of a third MST family member MST3. Intriguingly, this newly described MST3-NDR1/2 axis promotes G 1 progression by stabilizing c-myc and preventing p21 accumulation, indicating a potential pro-tumorigenic role for NDR kinases. Here, we discuss these novel cell cycle functions of NDR kinases in a broader context and elaborate on possible explanations for the opposing functions of NDR kinases in normal and tumor biology.

Reverse engineering and identification in systems biology: strategies, perspectives and challenges.

PubMed

Villaverde, Alejandro F; Banga, Julio R

2014-02-06

The interplay of mathematical modelling with experiments is one of the central elements in systems biology. The aim of reverse engineering is to infer, analyse and understand, through this interplay, the functional and regulatory mechanisms of biological systems. Reverse engineering is not exclusive of systems biology and has been studied in different areas, such as inverse problem theory, machine learning, nonlinear physics, (bio)chemical kinetics, control theory and optimization, among others. However, it seems that many of these areas have been relatively closed to outsiders. In this contribution, we aim to compare and highlight the different perspectives and contributions from these fields, with emphasis on two key questions: (i) why are reverse engineering problems so hard to solve, and (ii) what methods are available for the particular problems arising from systems biology?

Biology doesn't waste energy: that's really smart

NASA Astrophysics Data System (ADS)

Vincent, Julian F. V.; Bogatyreva, Olga; Bogatyrev, Nikolaj

2006-03-01

Biology presents us with answers to design problems that we suspect would be very useful if only we could implement them successfully. We use the Russian theory of problem solving - TRIZ - in a novel way to provide a system for analysis and technology transfer. The analysis shows that whereas technology uses energy as the main means of solving technical problems, biology uses information and structure. Biology is also strongly hierarchical. The suggestion is that smart technology in hierarchical structures can help us to design much more efficient technology. TRIZ also suggests that biological design is autonomous and can be defined by the prefix "self-" with any function. This autonomy extends to the control system, so that the sensor is commonly also the actuator, resulting in simpler systems and greater reliability.

Synaptic plasticity and memory functions achieved in a WO3-x-based nanoionics device by using the principle of atomic switch operation

NASA Astrophysics Data System (ADS)

Yang, Rui; Terabe, Kazuya; Yao, Yiping; Tsuruoka, Tohru; Hasegawa, Tsuyoshi; Gimzewski, James K.; Aono, Masakazu

2013-09-01

A compact neuromorphic nanodevice with inherent learning and memory properties emulating those of biological synapses is the key to developing artificial neural networks rivaling their biological counterparts. Experimental results showed that memorization with a wide time scale from volatile to permanent can be achieved in a WO3-x-based nanoionics device and can be precisely and cumulatively controlled by adjusting the device’s resistance state and input pulse parameters such as the amplitude, interval, and number. This control is analogous to biological synaptic plasticity including short-term plasticity, long-term potentiation, transition from short-term memory to long-term memory, forgetting processes for short- and long-term memory, learning speed, and learning history. A compact WO3-x-based nanoionics device with a simple stacked layer structure should thus be a promising candidate for use as an inorganic synapse in artificial neural networks due to its striking resemblance to the biological synapse.

Novel biomaterials: plasma-enabled nanostructures and functions

NASA Astrophysics Data System (ADS)

Levchenko, Igor; Keidar, Michael; Cvelbar, Uroš; Mariotti, Davide; Mai-Prochnow, Anne; Fang, Jinghua; (Ken Ostrikov, Kostya

2016-07-01

Material processing techniques utilizing low-temperature plasmas as the main process tool feature many unique capabilities for the fabrication of various nanostructured materials. As compared with the neutral-gas based techniques and methods, the plasma-based approaches offer higher levels of energy and flux controllability, often leading to higher quality of the fabricated nanomaterials and sometimes to the synthesis of the hierarchical materials with interesting properties. Among others, nanoscale biomaterials attract significant attention due to their special properties towards the biological materials (proteins, enzymes), living cells and tissues. This review briefly examines various approaches based on the use of low-temperature plasma environments to fabricate nanoscale biomaterials exhibiting high biological activity, biological inertness for drug delivery system, and other features of the biomaterials make them highly attractive. In particular, we briefly discuss the plasma-assisted fabrication of gold and silicon nanoparticles for bio-applications; carbon nanoparticles for bioimaging and cancer therapy; carbon nanotube-based platforms for enzyme production and bacteria growth control, and other applications of low-temperature plasmas in the production of biologically-active materials.

p53 as Batman: using a movie plot to understand control of the cell cycle.

PubMed

Gadi, Nikhita; Foley, Sage E; Nowey, Mark; Plopper, George E

2013-04-16

This Teaching Resource provides and describes a two-part classroom exercise to help students understand control of the cell cycle, with a focus on the transcription factor p53, the E3 ubiquitin ligase Mdm2, the Mdm2 inhibitor ARF, the kinases ATM and ATR, the kinase Chk2, and the cell cycle inhibitor p21(Cip1). Students use characters and scenes from the movie The Dark Knight to represent elements of the cell cycle control machinery, then they apply these characters and scenes to translate a primary research article on p53 function into a new movie scene in the "Batman universe." This exercise is appropriate for college-level courses in cell biology and cancer biology and requires students to have a background in introductory cell biology. Explicit learning outcomes and associated assessment methods are provided, as well as slides, student assignments, the primary research article, and an instructor's guide for the exercise.

Selection of reference genes for RT-qPCR analysis in a predatory biological control agent, Coleomegilla maculata (Coleoptera: Coccinellidae).

PubMed

Yang, Chunxiao; Pan, Huipeng; Noland, Jeffrey Edward; Zhang, Deyong; Zhang, Zhanhong; Liu, Yong; Zhou, Xuguo

2015-12-10

Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) is a reliable technique for quantifying gene expression across various biological processes, of which requires a set of suited reference genes to normalize the expression data. Coleomegilla maculata (Coleoptera: Coccinellidae), is one of the most extensively used biological control agents in the field to manage arthropod pest species. In this study, expression profiles of 16 housekeeping genes selected from C. maculata were cloned and investigated. The performance of these candidates as endogenous controls under specific experimental conditions was evaluated by dedicated algorithms, including geNorm, Normfinder, BestKeeper, and ΔCt method. In addition, RefFinder, a comprehensive platform integrating all the above-mentioned algorithms, ranked the overall stability of these candidate genes. As a result, various sets of suitable reference genes were recommended specifically for experiments involving different tissues, developmental stages, sex, and C. maculate larvae treated with dietary double stranded RNA. This study represents the critical first step to establish a standardized RT-qPCR protocol for the functional genomics research in a ladybeetle C. maculate. Furthermore, it lays the foundation for conducting ecological risk assessment of RNAi-based gene silencing biotechnologies on non-target organisms; in this case, a key predatory biological control agent.

Zinc in Cellular Regulation: The Nature and Significance of "Zinc Signals".

PubMed

Maret, Wolfgang

2017-10-31

In the last decade, we witnessed discoveries that established Zn 2+ as a second major signalling metal ion in the transmission of information within cells and in communication between cells. Together with Ca 2+ and Mg 2+ , Zn 2+ covers biological regulation with redox-inert metal ions over many orders of magnitude in concentrations. The regulatory functions of zinc ions, together with their functions as a cofactor in about three thousand zinc metalloproteins, impact virtually all aspects of cell biology. This article attempts to define the regulatory functions of zinc ions, and focuses on the nature of zinc signals and zinc signalling in pathways where zinc ions are either extracellular stimuli or intracellular messengers. These pathways interact with Ca 2+ , redox, and phosphorylation signalling. The regulatory functions of zinc require a complex system of precise homeostatic control for transients, subcellular distribution and traffic, organellar homeostasis, and vesicular storage and exocytosis of zinc ions.

Controlled confinement of DNA at the nanoscale: nanofabrication and surface bio-functionalization

PubMed Central

Palma, Matteo; Abramson, Justin; Gorodetsky, Alon; Nuckolls, Colin; Sheetz, Michael P.; Wind, Shalom J.; Hone, James

2012-01-01

Nanopatterned arrays of biomolecules are a powerful tool to address fundamental issues in many areas of biology. DNA nanoarrays, in particular, are of interest in the study of both DNA-protein interactions as well as for biodiagnostic investigations. In this context, achieving a highly specific nanoscale assembly of oligonulceotides at surfaces is critical. In this chapter we describe a method to control the immobilization of DNA on nanopatterned surfaces: the nanofabrication and the bio-functionalization involved in the process will be discussed. PMID:21674372

Molecularly Engineered Polymer-Based Systems in Drug Delivery and Regenerative Medicine.

PubMed

Piluso, Susanna; Soultan, Al Halifa; Patterson, Jennifer

2017-01-01

Polymer-based systems are attractive in drug delivery and regenerative medicine due to the possibility of tailoring their properties and functions to a specific application. The present review provides several examples of molecularly engineered polymer systems, including stimuli responsive polymers and supramolecular polymers. The advent of controlled polymerization techniques has enabled the preparation of polymers with controlled molecular weight and well-defined architecture. By using these techniques coupled to orthogonal chemical modification reactions, polymers can be molecularly engineered to incorporate functional groups able to respond to small changes in the local environment or to a specific biological signal. This review highlights the properties and applications of stimuli-responsive systems and polymer therapeutics, such as polymer-drug conjugates, polymer-protein conjugates, polymersomes, and hyperbranched systems. The applications of polymeric membranes in regenerative medicine are also discussed. The examples presented in this review suggest that the combination of membranes with polymers that are molecularly engineered to respond to specific biological functions could be relevant in the field of regenerative medicine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Hyperbranched polyglycerols at the biointerface

NASA Astrophysics Data System (ADS)

Moore, Eli; Thissen, Helmut; Voelcker, Nicolas H.

2013-08-01

The control over biointerfacial interactions is the key to a broad range of biomedical applications, ranging from implantable devices to drug delivery and nanomedicine. In many of these applications, coatings are required that reduce or prevent non-specific interactions with the biological environment, while at the same time presenting specific bioactive signals. Whilst surface coatings based on polymers such as poly(ethylene glycol) (PEG) have been used successfully, many limitations persist in regard to the biocompatibility, stability and functionality of state-of-the-art polymer coatings. Most of these limitations are related to the fact that, typically, linear polymers are used with associated limited chemical functionality. Here, we examine the development of hyperbranched polyglycerols (HPGs) as promising candidates for the replacement of traditional linear polymers, such as the chemically analogous PEG, for the control of biointerfacial interactions. HPGs are highly branched globular molecules that exhibit a high valency, allow easy access to a variety of functionalities and can present biologically active signals. In this review, a comprehensive overview is provided with respect to the history, synthetic strategies, modifications and applications of HPGs.

Biological Basis For Computer Vision: Some Perspectives

NASA Astrophysics Data System (ADS)

Gupta, Madan M.

1990-03-01

Using biology as a basis for the development of sensors, devices and computer vision systems is a challenge to systems and vision scientists. It is also a field of promising research for engineering applications. Biological sensory systems, such as vision, touch and hearing, sense different physical phenomena from our environment, yet they possess some common mathematical functions. These mathematical functions are cast into the neural layers which are distributed throughout our sensory regions, sensory information transmission channels and in the cortex, the centre of perception. In this paper, we are concerned with the study of the biological vision system and the emulation of some of its mathematical functions, both retinal and visual cortex, for the development of a robust computer vision system. This field of research is not only intriguing, but offers a great challenge to systems scientists in the development of functional algorithms. These functional algorithms can be generalized for further studies in such fields as signal processing, control systems and image processing. Our studies are heavily dependent on the the use of fuzzy - neural layers and generalized receptive fields. Building blocks of such neural layers and receptive fields may lead to the design of better sensors and better computer vision systems. It is hoped that these studies will lead to the development of better artificial vision systems with various applications to vision prosthesis for the blind, robotic vision, medical imaging, medical sensors, industrial automation, remote sensing, space stations and ocean exploration.

Centrin 3 is an inhibitor of centrosomal Mps1 and antagonizes centrin 2 function.

PubMed

Sawant, Dwitiya B; Majumder, Shubhra; Perkins, Jennifer L; Yang, Ching-Hui; Eyers, Patrick A; Fisk, Harold A

2015-11-01

Centrins are a family of small, calcium-binding proteins with diverse cellular functions that play an important role in centrosome biology. We previously identified centrin 2 and centrin 3 (Cetn2 and Cetn3) as substrates of the protein kinase Mps1. However, although Mps1 phosphorylation sites control the function of Cetn2 in centriole assembly and promote centriole overproduction, Cetn2 and Cetn3 are not functionally interchangeable, and we show here that Cetn3 is both a biochemical inhibitor of Mps1 catalytic activity and a biological inhibitor of centrosome duplication. In vitro, Cetn3 inhibits Mps1 autophosphorylation at Thr-676, a known site of T-loop autoactivation, and interferes with Mps1-dependent phosphorylation of Cetn2. The cellular overexpression of Cetn3 attenuates the incorporation of Cetn2 into centrioles and centrosome reduplication, whereas depletion of Cetn3 generates extra centrioles. Finally, overexpression of Cetn3 reduces Mps1 Thr-676 phosphorylation at centrosomes, and mimicking Mps1-dependent phosphorylation of Cetn2 bypasses the inhibitory effect of Cetn3, suggesting that the biological effects of Cetn3 are due to the inhibition of Mps1 function at centrosomes. © 2015 Sawant et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Characteristics of microbial community functional structure of a biological coking wastewater treatment system.

PubMed

Joshi, Dev Raj; Zhang, Yu; Zhang, Hong; Gao, Yingxin; Yang, Min

2018-01-01

Nitrogenous heterocyclic compounds are key pollutants in coking wastewater; however, the functional potential of microbial communities for biodegradation of such contaminants during biological treatment is still elusive. Herein, a high throughput functional gene array (GeoChip 5.0) in combination with Illumina HiSeq2500 sequencing was used to compare and characterize the microbial community functional structure in a long run (500days) bench scale bioreactor treating coking wastewater, with a control system treating synthetic wastewater. Despite the inhibitory toxic pollutants, GeoChip 5.0 detected almost all key functional gene (average 61,940 genes) categories in the coking wastewater sludge. With higher abundance, aromatic ring cleavage dioxygenase genes including multi ring1,2diox; one ring2,3diox; catechol represented significant functional potential for degradation of aromatic pollutants which was further confirmed by Illumina HiSeq2500 analysis results. Response ratio analysis revealed that three nitrogenous compound degrading genes- nbzA (nitro-aromatics), tdnB (aniline), and scnABC (thiocyanate) were unique for coking wastewater treatment, which might be strong cause to increase ammonia level during the aerobic process. Additionally, HiSeq2500 elucidated carbozole and isoquinoline degradation genes in the system. These findings expanded our understanding on functional potential of microbial communities to remove organic nitrogenous pollutants; hence it will be useful in optimization strategies for biological treatment of coking wastewater. Copyright © 2017. Published by Elsevier B.V.

What is the role of curvature on the properties of nanomaterials for biomedical applications?

PubMed Central

Solveyra, Estefania Gonzalez

2015-01-01

The use of nanomaterials for drug delivery and theranostics applications is a promising paradigm in nanomedicine, as it brings together the best features of nanotechnolgy, molecular biology and medicine. To fully exploit the synergistic potential of such interdisciplinary strategy, a comprehensive description of the interactions at the interface between nanomaterials and biological systems is not only crucial, but also mandatory. Routine strategies to engineer nanomaterial-based drugs comprise modifying their surface with biocompatible and targeting ligands, in many cases resorting to modular approaches that assume additive behavior. However, emergent behavior can be observed when combining confinement and curvature. The final properties of functionalized nanomaterials become dependent not only on the properties of their constituents but also on the geometry of the nano-bio interface, and on the local molecular environment. Modularity no longer holds, and the coupling between interactions, chemical equilibrium and molecular organization has to be directly addressed in order to design smart nanomaterials with controlled spatial functionalization envisioning optimized biomedical applications. Nanoparticle’s curvature becomes an integral part of the design strategy, enabling to control and engineer the chemical and surface properties with molecular precision. Understanding how NP size, morphology, and surface chemistry are interrelated will put us one step closer to engineering nanobiomaterials capable of mimicking biological structures and their behaviors, paving the way into applications and the possibility to elucidate the use of curvature by biological systems. PMID:26310432

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.

Protein Delivery into Plant Cells: Toward In vivo Structural Biology

PubMed Central

Cedeño, Cesyen; Pauwels, Kris; Tompa, Peter

2017-01-01

Understanding the biologically relevant structural and functional behavior of proteins inside living plant cells is only possible through the combination of structural biology and cell biology. The state-of-the-art structural biology techniques are typically applied to molecules that are isolated from their native context. Although most experimental conditions can be easily controlled while dealing with an isolated, purified protein, a serious shortcoming of such in vitro work is that we cannot mimic the extremely complex intracellular environment in which the protein exists and functions. Therefore, it is highly desirable to investigate proteins in their natural habitat, i.e., within live cells. This is the major ambition of in-cell NMR, which aims to approach structure-function relationship under true in vivo conditions following delivery of labeled proteins into cells under physiological conditions. With a multidisciplinary approach that includes recombinant protein production, confocal fluorescence microscopy, nuclear magnetic resonance (NMR) spectroscopy and different intracellular protein delivery strategies, we explore the possibility to develop in-cell NMR studies in living plant cells. While we provide a comprehensive framework to set-up in-cell NMR, we identified the efficient intracellular introduction of isotope-labeled proteins as the major bottleneck. Based on experiments with the paradigmatic intrinsically disordered proteins (IDPs) Early Response to Dehydration protein 10 and 14, we also established the subcellular localization of ERD14 under abiotic stress. PMID:28469623

[Biological security confronting bioterrorism].

PubMed

Suárez Fernández, Guillermo

2002-01-01

A review is made on Biosecurity at both local and global level in relationship with Bioterrorism as a real threat and its control and prevention. The function of the network of High Security Laboratories around the world able to make immediate diagnosis, research on vaccines, fundamental and urgent epidemiological studies, conform a steady basis to control natural infections and also the possible bioterrorism attacks.

Bt crops producing Cry1Ac, Cry2Ab and Cry1F do not harm the green lacewing, chrysoperla rufilabris

USDA-ARS?s Scientific Manuscript database

The biological control function provided by natural enemies is regarded as a protection goal that should not be harmed by the application of any new pest management tool. Plants producing Cry proteins from the bacterium, Bacillus thuringiensis (Bt), have become a major tactic for controlling pest Le...

Systematic, spatial imaging of large multimolecular assemblies and the emerging principles of supramolecular order in biological systems

PubMed Central

Schubert, Walter

2013-01-01

Understanding biological systems at the level of their relational (emergent) molecular properties in functional protein networks relies on imaging methods, able to spatially resolve a tissue or a cell as a giant, non-random, topologically defined collection of interacting supermolecules executing myriads of subcellular mechanisms. Here, the development and findings of parameter-unlimited functional super-resolution microscopy are described—a technology based on the fluorescence imaging cycler (IC) principle capable of co-mapping thousands of distinct biomolecular assemblies at high spatial resolution and differentiation (<40 nm distances). It is shown that the subcellular and transcellular features of such supermolecules can be described at the compositional and constitutional levels; that the spatial connection, relational stoichiometry, and topology of supermolecules generate hitherto unrecognized functional self-segmentation of biological tissues; that hierarchical features, common to thousands of simultaneously imaged supermolecules, can be identified; and how the resulting supramolecular order relates to spatial coding of cellular functionalities in biological systems. A large body of observations with IC molecular systems microscopy collected over 20 years have disclosed principles governed by a law of supramolecular segregation of cellular functionalities. This pervades phenomena, such as exceptional orderliness, functional selectivity, combinatorial and spatial periodicity, and hierarchical organization of large molecular systems, across all species investigated so far. This insight is based on the high degree of specificity, selectivity, and sensitivity of molecular recognition processes for fluorescence imaging beyond the spectral resolution limit, using probe libraries controlled by ICs. © 2013 The Authors. Journal of Molecular Recognition published by John Wiley & Sons, Ltd. PMID:24375580

Trends and Controls of inter-annual Variability in the Carbon Budget of Terrestrial Ecosystems

NASA Astrophysics Data System (ADS)

Cescatti, A.; Marcolla, B.

2014-12-01

The climate sensitivity of the terrestrial carbon budget will substantially affect the sign and strength of the land-climate feedbacks and the future climate trajectories. Current trends in the inter-annual variability of terrestrial carbon fluxes (IAV) may contribute to clarify the relative role of physical and biological controls of ecosystem responses to climate change. For this purpose we investigated how recent climate variability has impacted the carbon fluxes at long-term FLUXNET sites. Using a novel method, the IAV has been factored out in climate induced variability (physical control), variability due to changes in ecosystem functioning (biological control) and the interaction of the two terms. The relative control of the main climatic drivers (temperature, water availability) on the physical and biological sources of IAV has been investigated using both site level fluxes and global gridded products generated from the up-scaling of flux data. Results of this analysis highlight the fundamental role of precipitation trends on the pattern of IAV in the last 30 years. Our findings on the spatial/temporal trends of IAV have been finally confirmed using the signal derived from the global network of atmospheric CO2 concentrations measurements.

Toxins, Targets, and Triggers: An Overview of Toxin-Antitoxin Biology.

PubMed

Harms, Alexander; Brodersen, Ditlev Egeskov; Mitarai, Namiko; Gerdes, Kenn

2018-06-07

Bacterial toxin-antitoxin (TA) modules are abundant genetic elements that encode a toxin protein capable of inhibiting cell growth and an antitoxin that counteracts the toxin. The majority of toxins are enzymes that interfere with translation or DNA replication, but a wide variety of molecular activities and cellular targets have been described. Antitoxins are proteins or RNAs that often control their cognate toxins through direct interactions and, in conjunction with other signaling elements, through transcriptional and translational regulation of TA module expression. Three major biological functions of TA modules have been discovered, post-segregational killing ("plasmid addiction"), abortive infection (bacteriophage immunity through altruistic suicide), and persister formation (antibiotic tolerance through dormancy). In this review, we summarize the current state of the field and highlight how multiple levels of regulation shape the conditions of toxin activation to achieve the different biological functions of TA modules. Copyright © 2018 Elsevier Inc. All rights reserved.

Click Chemistry Mediated Functionalization of Vertical Nanowires for Biological Applications.

PubMed

Vutti, Surendra; Schoffelen, Sanne; Bolinsson, Jessica; Buch-Månson, Nina; Bovet, Nicolas; Nygård, Jesper; Martinez, Karen L; Meldal, Morten

2016-01-11

Semiconductor nanowires (NWs) are gaining significant importance in various biological applications, such as biosensing and drug delivery. Efficient and controlled immobilization of biomolecules on the NW surface is crucial for many of these applications. Here, we present for the first time the use of the Cu(I) -catalyzed alkyne-azide cycloaddition and its strain-promoted variant for the covalent functionalization of vertical NWs with peptides and proteins. The potential of the approach was demonstrated in two complementary applications of measuring enzyme activity and protein binding, which is of general interest for biological studies. The attachment of a peptide substrate provided NW arrays for the detection of protease activity. In addition, green fluorescent protein was immobilized in a site-specific manner and recognized by antibody binding to demonstrate the proof-of-concept for the use of covalently modified NWs for diagnostic purposes using minute amounts of material. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Evolution viewed from physics, physiology and medicine.

PubMed

Noble, Denis

2017-10-06

Stochasticity is harnessed by organisms to generate functionality. Randomness does not, therefore, necessarily imply lack of function or 'blind chance' at higher levels. In this respect, biology must resemble physics in generating order from disorder. This fact is contrary to Schrödinger's idea of biology generating phenotypic order from molecular- level order, which inspired the central dogma of molecular biology. The order originates at higher levels, which constrain the components at lower levels. We now know that this includes the genome, which is controlled by patterns of transcription factors and various epigenetic and reorganization mechanisms. These processes can occur in response to environmental stress, so that the genome becomes 'a highly sensitive organ of the cell' (McClintock). Organisms have evolved to be able to cope with many variations at the molecular level. Organisms also make use of physical processes in evolution and development when it is possible to arrive at functional development without the necessity to store all information in DNA sequences. This view of development and evolution differs radically from that of neo-Darwinism with its emphasis on blind chance as the origin of variation. Blind chance is necessary, but the origin of functional variation is not at the molecular level. These observations derive from and reinforce the principle of biological relativity, which holds that there is no privileged level of causation. They also have important implications for medical science.

Biogenic Magnetite and EMF Effects

NASA Astrophysics Data System (ADS)

Kirschvink, Joseph L.

1996-03-01

Magnetite biomineralization is a genetically-controlled biochemical process through which organisms make perfect ferrimagnetic crystals, usually of single magnetic domain size. This process is an ancient one, having evolved about 2 billion years ago in the magnetotactic bacteria, and presumably was incorporated in the genome of higher organisms, including humans. During this time, DNA replication, protein synthesis, and many other biochemical processes have functioned in the presence of strong static fields of up to 400 mT adjacent to these magnetosomes without any obvious deleterious effects. Recent behavioral experiments using short but strong magnetic pulses in honeybees and birds demonstrates that ferromagnetic materials are involved in the sensory transduction of geomagnetic field information to the nervous system, and both behavioral and direct electrophysiological experiments indicate sensitivity thresholds to DC magnetic fields down to a few nT. However, far more biogenic magnetite is present in animal tissues than is needed for magnetoreception, and the biological function of this extra material is unknown. The presence of ferromagnetic materials in biological systems could provide physical transduction mechanisms for ELF magnetic fields, as well for microwave radiation in the .5 to 10 GHz band where magnetite has its peak ferromagnetic resonance. Elucidation of the cellular ultrastructure and biological function(s) of magnetite might help resolve the question of whether anthropogenic EMFs can cause deleterious biological effects. This work has been supported by grants from the NIH and EPRI.

Robotics-inspired biology.

PubMed

Gravish, Nick; Lauder, George V

2018-03-29

For centuries, designers and engineers have looked to biology for inspiration. Biologically inspired robots are just one example of the application of knowledge of the natural world to engineering problems. However, recent work by biologists and interdisciplinary teams have flipped this approach, using robots and physical models to set the course for experiments on biological systems and to generate new hypotheses for biological research. We call this approach robotics-inspired biology; it involves performing experiments on robotic systems aimed at the discovery of new biological phenomena or generation of new hypotheses about how organisms function that can then be tested on living organisms. This new and exciting direction has emerged from the extensive use of physical models by biologists and is already making significant advances in the areas of biomechanics, locomotion, neuromechanics and sensorimotor control. Here, we provide an introduction and overview of robotics-inspired biology, describe two case studies and suggest several directions for the future of this exciting new research area. © 2018. Published by The Company of Biologists Ltd.

Trophic hierarchies illuminated via amino acid isotopic analysis

USDA-ARS?s Scientific Manuscript database

This research addresses the problem of discerning whether natural enemies in agricultural systems are actually suppressing pest populations (or simply eating other predators). Knowing the ecological function of natural enemies (particularly arthropods) is an integral part of biological control progr...

76 FR 38404 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-30

...: Vascular Biology. Date: July 11, 2011. Time: 12 p.m. to 2 p.m. Agenda: To review and evaluate grant... Scientific Review Special Emphasis Panel, PAR-10-266 Dynamics and Functions of NEDD8 In Cellular Control...

Bioinspired nanovalves with selective permeability and pH sensitivity

NASA Astrophysics Data System (ADS)

Zheng, Z.; Huang, X.; Schenderlein, M.; Moehwald, H.; Xu, G.-K.; Shchukin, D. G.

2015-01-01

Biological systems with controlled permeability and release functionality, which are among the successful examples of living beings to survive in evolution, have attracted intensive investigation and have been mimicked due to their broad spectrum of applications. We present in this work, for the first time, an example of nuclear pore complexes (NPCs)-inspired controlled release system that exhibits on-demand release of angstrom-sized molecules. We do so in a cost-effective way by stabilizing porous cobalt basic carbonates as nanovalves and realizing pH-sensitive release of entrapped subnano cargo. The proof-of-concept work also consists of the establishment of two mathematical models to explain the selective permeability of the nanovalves. Finally, gram-sized (or larger) quantities of the bio-inspired controlled release system can be synthesized through a scaling-up strategy, which opens up opportunities for controlled release of functional molecules in wider practical applications.Biological systems with controlled permeability and release functionality, which are among the successful examples of living beings to survive in evolution, have attracted intensive investigation and have been mimicked due to their broad spectrum of applications. We present in this work, for the first time, an example of nuclear pore complexes (NPCs)-inspired controlled release system that exhibits on-demand release of angstrom-sized molecules. We do so in a cost-effective way by stabilizing porous cobalt basic carbonates as nanovalves and realizing pH-sensitive release of entrapped subnano cargo. The proof-of-concept work also consists of the establishment of two mathematical models to explain the selective permeability of the nanovalves. Finally, gram-sized (or larger) quantities of the bio-inspired controlled release system can be synthesized through a scaling-up strategy, which opens up opportunities for controlled release of functional molecules in wider practical applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr06378c

Selective Enhancement of Nucleases by Polyvalent DNA-Functionalized Gold Nanoparticles

PubMed Central

Prigodich, Andrew E.; Alhasan, Ali H.

2011-01-01

We demonstrate that polyvalent DNA-functionalized gold nanoparticles (DNA-Au NPs) selectively enhance Ribonuclease H (RNase H) activity, while inhibiting most biologically relevant nucleases. This combination of properties is particularly interesting in the context of gene regulation, since high RNase H activity results in rapid mRNA degradation and general nuclease inhibition results in high biological stability. We investigate the mechanism of selective RNase H activation and find that the high DNA density of DNA-Au NPs is responsible for this unusual behavior. This work adds to our understanding of polyvalent DNA-Au NPs as gene regulation agents, and suggests a new model for selectively controlling protein-nanoparticle interactions. PMID:21268581

Cell biology of spinocerebellar ataxia.

PubMed

Orr, Harry T

2012-04-16

Ataxia is a neurological disorder characterized by loss of control of body movements. Spinocerebellar ataxia (SCA), previously known as autosomal dominant cerebellar ataxia, is a biologically robust group of close to 30 progressive neurodegenerative diseases. Six SCAs, including the more prevalent SCA1, SCA2, SCA3, and SCA6 along with SCA7 and SCA17 are caused by expansion of a CAG repeat that encodes a polyglutamine tract in the affected protein. How the mutated proteins in these polyglutamine SCAs cause disease is highly debated. Recent work suggests that the mutated protein contributes to pathogenesis within the context of its "normal" cellular function. Thus, understanding the cellular function of these proteins could aid in the development of therapeutics.

Silk-polypyrrole biocompatible actuator performance under biologically relevant conditions

NASA Astrophysics Data System (ADS)

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

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

Mammalian synthetic biology for studying the cell.

PubMed

Mathur, Melina; Xiang, Joy S; Smolke, Christina D

2017-01-02

Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

Two poplar-associated bacterial isolates induce additive favorable responses in a constructed plant-microbiome system

DOE PAGES

Jawdy, Sara S.; Gunter, Lee E.; Engle, Nancy L.; ...

2016-04-26

Here, the biological function of the plant-microbiome system is the result of contributions from the host plant and microbiome members. In this work we study the function of a simplified community consisting of Pseudomonas and Burkholderia bacterial strains isolated from Populus hosts and inoculated on axenic Populus cutting in controlled laboratory conditions. Inoculation individually with either bacterial isolate increased root growth relative to uninoculated controls. Root area, photosynthetic efficiency, gene expression and metabolite expression data in individual and dual inoculated treatments indicate that the effects of these bacteria are unique and additive, suggesting that the function of a microbiome communitymore » may be predicted from the additive functions of the individual members.« less

Organelle Communication at Membrane Contact Sites (MCS): From Curiosity to Center Stage in Cell Biology and Biomedical Research.

PubMed

Simmen, Thomas; Tagaya, Mitsuo

2017-01-01

Cell biology has long recognized that organelles can communicate with each other. Initially, such communication was thought to occur primarily via vesicular trafficking between biochemically distinct organelles. However, studies starting in the 1970s on lipid metabolism have unearthed another way how organelles can communicate and have spawned the field of membrane contact sites (MCS). While, initially, MCS had been recognized as fluid entities that mediate lipid and ion transport in an ad hoc manner, more recently MCS have been found to depend on protein-protein interactions that control themselves a variety of MCS functions. As a result, the cell biological definition of an intracellular organelle as an isolated membrane compartment is now being revised. Accordingly, the organelle definition now describes organelles as dynamic membrane compartments that function in a milieu of coordinated contacts with other organelles. Through these mercurial functions, MCS dictate the function of organelles to a large extent but also play important roles in a number of diseases, including type 2 diabetes, neurodegenerative diseases, infections, and cancer. This book assembles reviews that describe our quickly evolving knowledge about organellar communication on MCS and the significance of MCS for disease.

Evolution of optimal Hill coefficients in nonlinear public goods games.

PubMed

Archetti, Marco; Scheuring, István

2016-10-07

In evolutionary game theory, the effect of public goods like diffusible molecules has been modelled using linear, concave, sigmoid and step functions. The observation that biological systems are often sigmoid input-output functions, as described by the Hill equation, suggests that a sigmoid function is more realistic. The Michaelis-Menten model of enzyme kinetics, however, predicts a concave function, and while mechanistic explanations of sigmoid kinetics exist, we lack an adaptive explanation: what is the evolutionary advantage of a sigmoid benefit function? We analyse public goods games in which the shape of the benefit function can evolve, in order to determine the optimal and evolutionarily stable Hill coefficients. We find that, while the dynamics depends on whether output is controlled at the level of the individual or the population, intermediate or high Hill coefficients often evolve, leading to sigmoid input-output functions that for some parameters are so steep to resemble a step function (an on-off switch). Our results suggest that, even when the shape of the benefit function is unknown, biological public goods should be modelled using a sigmoid or step function rather than a linear or concave function. Copyright © 2016 Elsevier Ltd. All rights reserved.

Controlled droplet microfluidic systems for multistep chemical and biological assays.

PubMed

Kaminski, T S; Garstecki, P

2017-10-16

Droplet microfluidics is a relatively new and rapidly evolving field of science focused on studying the hydrodynamics and properties of biphasic flows at the microscale, and on the development of systems for practical applications in chemistry, biology and materials science. Microdroplets present several unique characteristics of interest to a broader research community. The main distinguishing features include (i) large numbers of isolated compartments of tiny volumes that are ideal for single cell or single molecule assays, (ii) rapid mixing and negligible thermal inertia that all provide excellent control over reaction conditions, and (iii) the presence of two immiscible liquids and the interface between them that enables new or exotic processes (the synthesis of new functional materials and structures that are otherwise difficult to obtain, studies of the functions and properties of lipid and polymer membranes and execution of reactions at liquid-liquid interfaces). The most frequent application of droplet microfluidics relies on the generation of large numbers of compartments either for ultrahigh throughput screens or for the synthesis of functional materials composed of millions of droplets or particles. Droplet microfluidics has already evolved into a complex field. In this review we focus on 'controlled droplet microfluidics' - a portfolio of techniques that provide convenient platforms for multistep complex reaction protocols and that take advantage of automated and passive methods of fluid handling on a chip. 'Controlled droplet microfluidics' can be regarded as a group of methods capable of addressing and manipulating droplets in series. The functionality and complexity of controlled droplet microfluidic systems can be positioned between digital microfluidics (DMF) addressing each droplet individually using 2D arrays of electrodes and ultrahigh throughput droplet microfluidics focused on the generation of hundreds of thousands or even millions of picoliter droplets that cannot be individually addressed by their location on a chip.

Mutual information estimation reveals global associations between stimuli and biological processes

PubMed Central

Suzuki, Taiji; Sugiyama, Masashi; Kanamori, Takafumi; Sese, Jun

2009-01-01

Background Although microarray gene expression analysis has become popular, it remains difficult to interpret the biological changes caused by stimuli or variation of conditions. Clustering of genes and associating each group with biological functions are often used methods. However, such methods only detect partial changes within cell processes. Herein, we propose a method for discovering global changes within a cell by associating observed conditions of gene expression with gene functions. Results To elucidate the association, we introduce a novel feature selection method called Least-Squares Mutual Information (LSMI), which computes mutual information without density estimaion, and therefore LSMI can detect nonlinear associations within a cell. We demonstrate the effectiveness of LSMI through comparison with existing methods. The results of the application to yeast microarray datasets reveal that non-natural stimuli affect various biological processes, whereas others are no significant relation to specific cell processes. Furthermore, we discover that biological processes can be categorized into four types according to the responses of various stimuli: DNA/RNA metabolism, gene expression, protein metabolism, and protein localization. Conclusion We proposed a novel feature selection method called LSMI, and applied LSMI to mining the association between conditions of yeast and biological processes through microarray datasets. In fact, LSMI allows us to elucidate the global organization of cellular process control. PMID:19208155

Neural circuits underlying mother’s voice perception predict social communication abilities in children

PubMed Central

Abrams, Daniel A.; Chen, Tianwen; Odriozola, Paola; Cheng, Katherine M.; Baker, Amanda E.; Padmanabhan, Aarthi; Ryali, Srikanth; Kochalka, John; Feinstein, Carl; Menon, Vinod

2016-01-01

The human voice is a critical social cue, and listeners are extremely sensitive to the voices in their environment. One of the most salient voices in a child’s life is mother's voice: Infants discriminate their mother’s voice from the first days of life, and this stimulus is associated with guiding emotional and social function during development. Little is known regarding the functional circuits that are selectively engaged in children by biologically salient voices such as mother’s voice or whether this brain activity is related to children’s social communication abilities. We used functional MRI to measure brain activity in 24 healthy children (mean age, 10.2 y) while they attended to brief (<1 s) nonsense words produced by their biological mother and two female control voices and explored relationships between speech-evoked neural activity and social function. Compared to female control voices, mother’s voice elicited greater activity in primary auditory regions in the midbrain and cortex; voice-selective superior temporal sulcus (STS); the amygdala, which is crucial for processing of affect; nucleus accumbens and orbitofrontal cortex of the reward circuit; anterior insula and cingulate of the salience network; and a subregion of fusiform gyrus associated with face perception. The strength of brain connectivity between voice-selective STS and reward, affective, salience, memory, and face-processing regions during mother’s voice perception predicted social communication skills. Our findings provide a novel neurobiological template for investigation of typical social development as well as clinical disorders, such as autism, in which perception of biologically and socially salient voices may be impaired. PMID:27185915

Neural circuits underlying mother's voice perception predict social communication abilities in children.

PubMed

Abrams, Daniel A; Chen, Tianwen; Odriozola, Paola; Cheng, Katherine M; Baker, Amanda E; Padmanabhan, Aarthi; Ryali, Srikanth; Kochalka, John; Feinstein, Carl; Menon, Vinod

2016-05-31

The human voice is a critical social cue, and listeners are extremely sensitive to the voices in their environment. One of the most salient voices in a child's life is mother's voice: Infants discriminate their mother's voice from the first days of life, and this stimulus is associated with guiding emotional and social function during development. Little is known regarding the functional circuits that are selectively engaged in children by biologically salient voices such as mother's voice or whether this brain activity is related to children's social communication abilities. We used functional MRI to measure brain activity in 24 healthy children (mean age, 10.2 y) while they attended to brief (<1 s) nonsense words produced by their biological mother and two female control voices and explored relationships between speech-evoked neural activity and social function. Compared to female control voices, mother's voice elicited greater activity in primary auditory regions in the midbrain and cortex; voice-selective superior temporal sulcus (STS); the amygdala, which is crucial for processing of affect; nucleus accumbens and orbitofrontal cortex of the reward circuit; anterior insula and cingulate of the salience network; and a subregion of fusiform gyrus associated with face perception. The strength of brain connectivity between voice-selective STS and reward, affective, salience, memory, and face-processing regions during mother's voice perception predicted social communication skills. Our findings provide a novel neurobiological template for investigation of typical social development as well as clinical disorders, such as autism, in which perception of biologically and socially salient voices may be impaired.

The Effects of Sex and Gender-Role Characteristics on Facets of Sociosexuality in Heterosexual Young Adults.

PubMed

Rammsayer, Thomas H; Borter, Natalie; Troche, Stefan J

2017-02-01

The present study was designed to systematically investigate the functional relationships among biological sex; masculine and feminine gender-role characteristics; and sociosexual behavior, attitude toward, and desire for uncommitted casual sex as three facets of sociosexual orientation. For this purpose, facets of sociosexuality were assessed by the Revised Sociosexual Orientation Inventory (SOI-R) and masculine and feminine gender-role characteristics were assessed by a revised German version of the Bem Sex-Role Inventory in 499 male and 958 female heterosexual young adults. Confirmatory factor analysis (CFA) and structural equation modeling (SEM) revealed differential mediating effects of masculine and feminine gender-role characteristics on the relationship between biological sex and the three facets of sociosexual orientation. Sociosexual behavior was shown to be primarily controlled by an individual's level of masculine gender-role characteristics irrespective of biological sex. Sociosexual desire was identified as being a sole function of biological sex with no indication for any effect of masculine or feminine gender-role characteristics, while sociosexual attitude was influenced by biological sex as well as by masculine and feminine gender-role characteristics to about the same extent.

Chemical roots of biological evolution: the origins of life as a process of development of autonomous functional systems

PubMed Central

Ruiz-Mirazo, Kepa; Briones, Carlos

2017-01-01

In recent years, an extension of the Darwinian framework is being considered for the study of prebiotic chemical evolution, shifting the attention from homogeneous populations of naked molecular species to populations of heterogeneous, compartmentalized and functionally integrated assemblies of molecules. Several implications of this shift of perspective are analysed in this critical review, both in terms of the individual units, which require an adequate characterization as self-maintaining systems with an internal organization, and also in relation to their collective and long-term evolutionary dynamics, based on competition, collaboration and selection processes among those complex individuals. On these lines, a concrete proposal for the set of molecular control mechanisms that must be coupled to bring about autonomous functional systems, at the interface between chemistry and biology, is provided. PMID:28446711

Chemical roots of biological evolution: the origins of life as a process of development of autonomous functional systems.

PubMed

Ruiz-Mirazo, Kepa; Briones, Carlos; de la Escosura, Andrés

2017-04-01

In recent years, an extension of the Darwinian framework is being considered for the study of prebiotic chemical evolution, shifting the attention from homogeneous populations of naked molecular species to populations of heterogeneous, compartmentalized and functionally integrated assemblies of molecules. Several implications of this shift of perspective are analysed in this critical review, both in terms of the individual units, which require an adequate characterization as self-maintaining systems with an internal organization, and also in relation to their collective and long-term evolutionary dynamics, based on competition, collaboration and selection processes among those complex individuals. On these lines, a concrete proposal for the set of molecular control mechanisms that must be coupled to bring about autonomous functional systems, at the interface between chemistry and biology, is provided. © 2017 The Authors.

Noncoding RNAs and the control of signalling via nuclear receptor regulation in health and disease.

PubMed

Cathcart, Paul; Lucchesi, Walter; Ottaviani, Silvia; De Giorgio, Alex; Krell, Jonathan; Stebbing, Justin; Castellano, Leandro

2015-08-01

Nuclear receptors belong to a superfamily of proteins that play central roles in human biology, orchestrating a large variety of biological functions in both health and disease. Understanding the interactions and regulatory pathways of NRs will allow development of potential therapeutic interventions for a multitude of disease processes. Non-coding RNAs have recently been discovered to have significant interactions with NR signalling pathways via a variety of biological connections. This review summarises the known interactions between ncRNAs and the NR superfamily in health, embryogenesis and a plethora of human diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Integrative structure modeling with the Integrative Modeling Platform.

PubMed

Webb, Benjamin; Viswanath, Shruthi; Bonomi, Massimiliano; Pellarin, Riccardo; Greenberg, Charles H; Saltzberg, Daniel; Sali, Andrej

2018-01-01

Building models of a biological system that are consistent with the myriad data available is one of the key challenges in biology. Modeling the structure and dynamics of macromolecular assemblies, for example, can give insights into how biological systems work, evolved, might be controlled, and even designed. Integrative structure modeling casts the building of structural models as a computational optimization problem, for which information about the assembly is encoded into a scoring function that evaluates candidate models. Here, we describe our open source software suite for integrative structure modeling, Integrative Modeling Platform (https://integrativemodeling.org), and demonstrate its use. © 2017 The Protein Society.

Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease.

PubMed

Modena, Brian D; Bleecker, Eugene R; Busse, William W; Erzurum, Serpil C; Gaston, Benjamin M; Jarjour, Nizar N; Meyers, Deborah A; Milosevic, Jadranka; Tedrow, John R; Wu, Wei; Kaminski, Naftali; Wenzel, Sally E

2017-06-01

Severe asthma (SA) is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of bronchial epithelial cells in individuals with asthma have provided biological insight and underscored possible mechanistic differences between individuals. Identify networks of genes reflective of underlying biological processes that define SA. Airway epithelial cell gene expression from 155 subjects with asthma and healthy control subjects in the Severe Asthma Research Program was analyzed by weighted gene coexpression network analysis to identify gene networks and profiles associated with SA and its specific characteristics (i.e., pulmonary function tests, quality of life scores, urgent healthcare use, and steroid use), which potentially identified underlying biological processes. A linear model analysis confirmed these findings while adjusting for potential confounders. Weighted gene coexpression network analysis constructed 64 gene network modules, including modules corresponding to T1 and T2 inflammation, neuronal function, cilia, epithelial growth, and repair mechanisms. Although no network selectively identified SA, genes in modules linked to epithelial growth and repair and neuronal function were markedly decreased in SA. Several hub genes of the epithelial growth and repair module were found located at the 17q12-21 locus, near a well-known asthma susceptibility locus. T2 genes increased with severity in those treated with corticosteroids but were also elevated in untreated, mild-to-moderate disease compared with healthy control subjects. T1 inflammation, especially when associated with increased T2 gene expression, was elevated in a subgroup of younger patients with SA. In this hypothesis-generating analysis, gene expression networks in relation to asthma severity provided potentially new insight into biological mechanisms associated with the development of SA and its phenotypes.

Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease

PubMed Central

Modena, Brian D.; Bleecker, Eugene R.; Busse, William W.; Erzurum, Serpil C.; Gaston, Benjamin M.; Jarjour, Nizar N.; Meyers, Deborah A.; Milosevic, Jadranka; Tedrow, John R.; Wu, Wei; Kaminski, Naftali

2017-01-01

Rationale: Severe asthma (SA) is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of bronchial epithelial cells in individuals with asthma have provided biological insight and underscored possible mechanistic differences between individuals. Objectives: Identify networks of genes reflective of underlying biological processes that define SA. Methods: Airway epithelial cell gene expression from 155 subjects with asthma and healthy control subjects in the Severe Asthma Research Program was analyzed by weighted gene coexpression network analysis to identify gene networks and profiles associated with SA and its specific characteristics (i.e., pulmonary function tests, quality of life scores, urgent healthcare use, and steroid use), which potentially identified underlying biological processes. A linear model analysis confirmed these findings while adjusting for potential confounders. Measurements and Main Results: Weighted gene coexpression network analysis constructed 64 gene network modules, including modules corresponding to T1 and T2 inflammation, neuronal function, cilia, epithelial growth, and repair mechanisms. Although no network selectively identified SA, genes in modules linked to epithelial growth and repair and neuronal function were markedly decreased in SA. Several hub genes of the epithelial growth and repair module were found located at the 17q12–21 locus, near a well-known asthma susceptibility locus. T2 genes increased with severity in those treated with corticosteroids but were also elevated in untreated, mild-to-moderate disease compared with healthy control subjects. T1 inflammation, especially when associated with increased T2 gene expression, was elevated in a subgroup of younger patients with SA. Conclusions: In this hypothesis-generating analysis, gene expression networks in relation to asthma severity provided potentially new insight into biological mechanisms associated with the development of SA and its phenotypes. PMID:27984699

Regenerative Engineering and Bionic Limbs.

PubMed

James, Roshan; Laurencin, Cato T

2015-03-01

Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counselling. There is no prosthesis that allows the amputees near-normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feed-back to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past thirty years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feed-back will be the important goals in regenerative engineering over the next two decades.

Regenerative Engineering and Bionic Limbs

PubMed Central

James, Roshan; Laurencin, Cato T.

2015-01-01

Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counselling. There is no prosthesis that allows the amputees near-normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feed-back to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past thirty years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feed-back will be the important goals in regenerative engineering over the next two decades. PMID:25983525

Reverse engineering and identification in systems biology: strategies, perspectives and challenges

PubMed Central

Villaverde, Alejandro F.; Banga, Julio R.

2014-01-01

The interplay of mathematical modelling with experiments is one of the central elements in systems biology. The aim of reverse engineering is to infer, analyse and understand, through this interplay, the functional and regulatory mechanisms of biological systems. Reverse engineering is not exclusive of systems biology and has been studied in different areas, such as inverse problem theory, machine learning, nonlinear physics, (bio)chemical kinetics, control theory and optimization, among others. However, it seems that many of these areas have been relatively closed to outsiders. In this contribution, we aim to compare and highlight the different perspectives and contributions from these fields, with emphasis on two key questions: (i) why are reverse engineering problems so hard to solve, and (ii) what methods are available for the particular problems arising from systems biology? PMID:24307566

Engineering responsive supramolecular biomaterials: Toward smart therapeutics.

PubMed

Webber, Matthew J

2016-09-01

Engineering materials using supramolecular principles enables generalizable and modular platforms that have tunable chemical, mechanical, and biological properties. Applying this bottom-up, molecular engineering-based approach to therapeutic design affords unmatched control of emergent properties and functionalities. In preparing responsive materials for biomedical applications, the dynamic character of typical supramolecular interactions facilitates systems that can more rapidly sense and respond to specific stimuli through a fundamental change in material properties or characteristics, as compared to cases where covalent bonds must be overcome. Several supramolecular motifs have been evaluated toward the preparation of "smart" materials capable of sensing and responding to stimuli. Triggers of interest in designing materials for therapeutic use include applied external fields, environmental changes, biological actuators, applied mechanical loading, and modulation of relative binding affinities. In addition, multistimuli-responsive routes can be realized that capture combinations of triggers for increased functionality. In sum, supramolecular engineering offers a highly functional strategy to prepare responsive materials. Future development and refinement of these approaches will improve precision in material formation and responsiveness, seek dynamic reciprocity in interactions with living biological systems, and improve spatiotemporal sensing of disease for better therapeutic deployment.

Monotone viable trajectories for functional differential inclusions

NASA Astrophysics Data System (ADS)

Haddad, Georges

This paper is a study on functional differential inclusions with memory which represent the multivalued version of retarded functional differential equations. The main result gives a necessary and sufficient equations. The main result gives a necessary and sufficient condition ensuring the existence of viable trajectories; that means trajectories remaining in a given nonempty closed convex set defined by given constraints the system must satisfy to be viable. Some motivations for this paper can be found in control theory where F( t, φ) = { f( t, φ, u)} uɛU is the set of possible velocities of the system at time t, depending on the past history represented by the function φ and on a control u ranging over a set U of controls. Other motivations can be found in planning procedures in microeconomics and in biological evolutions where problems with memory do effectively appear in a multivalued version. All these models require viability constraints represented by a closed convex set.

Designing and testing a classroom curriculum to teach preschoolers about the biology of physical activity: The respiration system as an underlying biological causal mechanism

NASA Astrophysics Data System (ADS)

Ewing, Tracy S.

The present study examined young children's understanding of respiration and oxygen as a source of vital energy underlying physical activity. Specifically, the purpose of the study was to explore whether a coherent biological theory, characterized by an understanding that bodily parts (heart and lungs) and processes (oxygen in respiration) as part of a biological system, can be taught as a foundational concept to reason about physical activity. The effects of a biology-based intervention curriculum designed to teach preschool children about bodily functions as a part of the respiratory system, the role of oxygen as a vital substance and how physical activity acts an energy source were examined. Participants were recruited from three private preschool classrooms (two treatment; 1 control) in Southern California and included a total of 48 four-year-old children (30 treatment; 18 control). Findings from this study suggested that young children could be taught relevant biological concepts about the role of oxygen in respiratory processes. Children who received biology-based intervention curriculum made significant gains in their understanding of the biology of respiration, identification of physical and sedentary activities. In addition these children demonstrated that coherence of conceptual knowledge was correlated with improved accuracy at activity identification and reasoning about the inner workings of the body contributing to endurance. Findings from this study provided evidence to support the benefits of providing age appropriate but complex coherent biological instruction to children in early childhood settings.

Electronic control of gene expression and cell behaviour in Escherichia coli through redox signalling

NASA Astrophysics Data System (ADS)

Tschirhart, Tanya; Kim, Eunkyoung; McKay, Ryan; Ueda, Hana; Wu, Hsuan-Chen; Pottash, Alex Eli; Zargar, Amin; Negrete, Alejandro; Shiloach, Joseph; Payne, Gregory F.; Bentley, William E.

2017-01-01

The ability to interconvert information between electronic and ionic modalities has transformed our ability to record and actuate biological function. Synthetic biology offers the potential to expand communication `bandwidth' by using biomolecules and providing electrochemical access to redox-based cell signals and behaviours. While engineered cells have transmitted molecular information to electronic devices, the potential for bidirectional communication stands largely untapped. Here we present a simple electrogenetic device that uses redox biomolecules to carry electronic information to engineered bacterial cells in order to control transcription from a simple synthetic gene circuit. Electronic actuation of the native transcriptional regulator SoxR and transcription from the PsoxS promoter allows cell response that is quick, reversible and dependent on the amplitude and frequency of the imposed electronic signals. Further, induction of bacterial motility and population based cell-to-cell communication demonstrates the versatility of our approach and potential to drive intricate biological behaviours.

Diversity and Evolution of the Phenazine Biosynthesis Pathway

USDA-ARS?s Scientific Manuscript database

Phenazines are versatile secondary metabolites of bacterial origin that function in biological control of plant pathogens and contribute to the ecological fitness and pathogenicity of the producing strains. In this study, we employed a collection of 94 strains having various geographic, environmenta...

Diversity and Evolution of the Phenazine Biosynthesis Pathway

USDA-ARS?s Scientific Manuscript database

Phenazines are versatile secondary metabolites of bacterial origin that function in biological control of plant pathogens and contribute to the ecological fitness and pathogenicity of the producing strains. In this study, we employed a collection of 94 strains of various geographic, environmental an...

Computational Modeling in Concert with Laboratory Studies: Application to B Cell Differentiation

EPA Science Inventory

Remediation is expensive, so accurate prediction of dose-response is important to help control costs. Dose response is a function of biological mechanisms. Computational models of these mechanisms improve the efficiency of research and provide the capability for prediction.

Systems Genetics Analysis of GWAS reveals Novel Associations between Key Biological Processes and Coronary Artery Disease

PubMed Central

Ghosh, Sujoy; Vivar, Juan; Nelson, Christopher P; Willenborg, Christina; Segrè, Ayellet V; Mäkinen, Ville-Petteri; Nikpay, Majid; Erdmann, Jeannette; Blankenberg, Stefan; O'Donnell, Christopher; März, Winfried; Laaksonen, Reijo; Stewart, Alexandre FR; Epstein, Stephen E; Shah, Svati H; Granger, Christopher B; Hazen, Stanley L; Kathiresan, Sekar; Reilly, Muredach P; Yang, Xia; Quertermous, Thomas; Samani, Nilesh J; Schunkert, Heribert; Assimes, Themistocles L; McPherson, Ruth

2016-01-01

Objective Genome-wide association (GWA) studies have identified multiple genetic variants affecting the risk of coronary artery disease (CAD). However, individually these explain only a small fraction of the heritability of CAD and for most, the causal biological mechanisms remain unclear. We sought to obtain further insights into potential causal processes of CAD by integrating large-scale GWA data with expertly curated databases of core human pathways and functional networks. Approaches and Results Employing pathways (gene sets) from Reactome, we carried out a two-stage gene set enrichment analysis strategy. From a meta-analyzed discovery cohort of 7 CADGWAS data sets (9,889 cases/11,089 controls), nominally significant gene-sets were tested for replication in a meta-analysis of 9 additional studies (15,502 cases/55,730 controls) from the CARDIoGRAM Consortium. A total of 32 of 639 Reactome pathways tested showed convincing association with CAD (replication p<0.05). These pathways resided in 9 of 21 core biological processes represented in Reactome, and included pathways relevant to extracellular matrix integrity, innate immunity, axon guidance, and signaling by PDRF, NOTCH, and the TGF-β/SMAD receptor complex. Many of these pathways had strengths of association comparable to those observed in lipid transport pathways. Network analysis of unique genes within the replicated pathways further revealed several interconnected functional and topologically interacting modules representing novel associations (e.g. semaphorin regulated axonal guidance pathway) besides confirming known processes (lipid metabolism). The connectivity in the observed networks was statistically significant compared to random networks (p<0.001). Network centrality analysis (‘degree’ and ‘betweenness’) further identified genes (e.g. NCAM1, FYN, FURIN etc.) likely to play critical roles in the maintenance and functioning of several of the replicated pathways. Conclusions These findings provide novel insights into how genetic variation, interpreted in the context of biological processes and functional interactions among genes, may help define the genetic architecture of CAD. PMID:25977570

A Keystone Ant Species Provides Robust Biological Control of the Coffee Berry Borer Under Varying Pest Densities.

PubMed

Morris, Jonathan R; Vandermeer, John; Perfecto, Ivette

2015-01-01

Species' functional traits are an important part of the ecological complexity that determines the provisioning of ecosystem services. In biological pest control, predator response to pest density variation is a dynamic trait that impacts the provision of this service in agroecosystems. When pest populations fluctuate, farmers relying on biocontrol services need to know how natural enemies respond to these changes. Here we test the effect of variation in coffee berry borer (CBB) density on the biocontrol efficiency of a keystone ant species (Azteca sericeasur) in a coffee agroecosystem. We performed exclosure experiments to measure the infestation rate of CBB released on coffee branches in the presence and absence of ants at four different CBB density levels. We measured infestation rate as the number of CBB bored into fruits after 24 hours, quantified biocontrol efficiency (BCE) as the proportion of infesting CBB removed by ants, and estimated functional response from ant attack rates, measured as the difference in CBB infestation between branches. Infestation rates of CBB on branches with ants were significantly lower (71%-82%) than on those without ants across all density levels. Additionally, biocontrol efficiency was generally high and did not significantly vary across pest density treatments. Furthermore, ant attack rates increased linearly with increasing CBB density, suggesting a Type I functional response. These results demonstrate that ants can provide robust biological control of CBB, despite variation in pest density, and that the response of predators to pest density variation is an important factor in the provision of biocontrol services. Considering how natural enemies respond to changes in pest densities will allow for more accurate biocontrol predictions and better-informed management of this ecosystem service in agroecosystems.

A Keystone Ant Species Provides Robust Biological Control of the Coffee Berry Borer Under Varying Pest Densities

PubMed Central

Morris, Jonathan R.; Vandermeer, John; Perfecto, Ivette

2015-01-01

Species’ functional traits are an important part of the ecological complexity that determines the provisioning of ecosystem services. In biological pest control, predator response to pest density variation is a dynamic trait that impacts the provision of this service in agroecosystems. When pest populations fluctuate, farmers relying on biocontrol services need to know how natural enemies respond to these changes. Here we test the effect of variation in coffee berry borer (CBB) density on the biocontrol efficiency of a keystone ant species (Azteca sericeasur) in a coffee agroecosystem. We performed exclosure experiments to measure the infestation rate of CBB released on coffee branches in the presence and absence of ants at four different CBB density levels. We measured infestation rate as the number of CBB bored into fruits after 24 hours, quantified biocontrol efficiency (BCE) as the proportion of infesting CBB removed by ants, and estimated functional response from ant attack rates, measured as the difference in CBB infestation between branches. Infestation rates of CBB on branches with ants were significantly lower (71%-82%) than on those without ants across all density levels. Additionally, biocontrol efficiency was generally high and did not significantly vary across pest density treatments. Furthermore, ant attack rates increased linearly with increasing CBB density, suggesting a Type I functional response. These results demonstrate that ants can provide robust biological control of CBB, despite variation in pest density, and that the response of predators to pest density variation is an important factor in the provision of biocontrol services. Considering how natural enemies respond to changes in pest densities will allow for more accurate biocontrol predictions and better-informed management of this ecosystem service in agroecosystems. PMID:26562676

The neural optimal control hierarchy for motor control

NASA Astrophysics Data System (ADS)

DeWolf, T.; Eliasmith, C.

2011-10-01

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

Humidity-controlled preparation of frozen-hydrated biological samples for cryogenic coherent x-ray diffraction microscopy

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

Takayama, Yuki; Nakasako, Masayoshi; RIKEN Harima Institute/SPring-8, 1-1-1 Kouto, Mikaduki, Sayo, Hyogo 679-5148

2012-05-15

Coherent x-ray diffraction microscopy (CXDM) has the potential to visualize the structures of micro- to sub-micrometer-sized biological particles, such as cells and organelles, at high resolution. Toward advancing structural studies on the functional states of such particles, here, we developed a system for the preparation of frozen-hydrated biological samples for cryogenic CXDM experiments. The system, which comprised a moist air generator, microscope, micro-injector mounted on a micromanipulator, custom-made sample preparation chamber, and flash-cooling device, allowed for the manipulation of sample particles in the relative humidity range of 20%-94%rh at 293 K to maintain their hydrated and functional states. Here, wemore » report the details of the system and the operation procedure, including its application to the preparation of a frozen-hydrated chloroplast sample. Sample quality was evaluated through a cryogenic CXDM experiment conducted at BL29XUL of SPring-8. Taking the performance of the system and the quality of the sample, the system was suitable to prepare frozen-hydrated biological samples for cryogenic CXDM experiments.« less

Stochastic Control and Numerical Methods with Applications to Communications. Game Theoretic/Subsolution to Importance Sampling for Rare Event Simulation

DTIC Science & Technology

2008-11-01

support to the value of the approach. 9. Scheduling and Control of Mobile Communications Networks with Randomly Time Varying Channels by Stability ...biological systems . Many examples arise in communications and queueing, due to the finite speed of signal transmission, the nonnegligible time required...without delays, the system state takes values in a subset of some finite -dimensional Euclidean space, and the control is a functional of the current

Network-based analysis of differentially expressed genes in cerebrospinal fluid (CSF) and blood reveals new candidate genes for multiple sclerosis

PubMed Central

Safari-Alighiarloo, Nahid; Taghizadeh, Mohammad; Tabatabaei, Seyyed Mohammad; Namaki, Saeed

2016-01-01

Background The involvement of multiple genes and missing heritability, which are dominant in complex diseases such as multiple sclerosis (MS), entail using network biology to better elucidate their molecular basis and genetic factors. We therefore aimed to integrate interactome (protein–protein interaction (PPI)) and transcriptomes data to construct and analyze PPI networks for MS disease. Methods Gene expression profiles in paired cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) samples from MS patients, sampled in relapse or remission and controls, were analyzed. Differentially expressed genes which determined only in CSF (MS vs. control) and PBMCs (relapse vs. remission) separately integrated with PPI data to construct the Query-Query PPI (QQPPI) networks. The networks were further analyzed to investigate more central genes, functional modules and complexes involved in MS progression. Results The networks were analyzed and high centrality genes were identified. Exploration of functional modules and complexes showed that the majority of high centrality genes incorporated in biological pathways driving MS pathogenesis. Proteasome and spliceosome were also noticeable in enriched pathways in PBMCs (relapse vs. remission) which were identified by both modularity and clique analyses. Finally, STK4, RB1, CDKN1A, CDK1, RAC1, EZH2, SDCBP genes in CSF (MS vs. control) and CDC37, MAP3K3, MYC genes in PBMCs (relapse vs. remission) were identified as potential candidate genes for MS, which were the more central genes involved in biological pathways. Discussion This study showed that network-based analysis could explicate the complex interplay between biological processes underlying MS. Furthermore, an experimental validation of candidate genes can lead to identification of potential therapeutic targets. PMID:28028462

Controlling chimeras

NASA Astrophysics Data System (ADS)

Bick, Christian; Martens, Erik A.

2015-03-01

Coupled phase oscillators model a variety of dynamical phenomena in nature and technological applications. Non-local coupling gives rise to chimera states which are characterized by a distinct part of phase-synchronized oscillators while the remaining ones move incoherently. Here, we apply the idea of control to chimera states: using gradient dynamics to exploit drift of a chimera, it will attain any desired target position. Through control, chimera states become functionally relevant; for example, the controlled position of localized synchrony may encode information and perform computations. Since functional aspects are crucial in (neuro-)biology and technology, the localized synchronization of a chimera state becomes accessible to develop novel applications. Based on gradient dynamics, our control strategy applies to any suitable observable and can be generalized to arbitrary dimensions. Thus, the applicability of chimera control goes beyond chimera states in non-locally coupled systems.

Biology, Bionomics and Molecular Biology of Anopheles sinensis Wiedemann 1828 (Diptera: Culicidae), Main Malaria Vector in China

PubMed Central

Feng, Xinyu; Zhang, Shaosen; Huang, Fang; Zhang, Li; Feng, Jun; Xia, Zhigui; Zhou, Hejun; Hu, Wei; Zhou, Shuisen

2017-01-01

China has set a goal to eliminate all malaria in the country by 2020, but it is unclear if current understanding of malaria vectors and transmission is sufficient to achieve this objective. Anopheles sinensis is the most widespread malaria vector specie in China, which is also responsible for vivax malaria outbreak in central China. We reviewed literature from 1954 to 2016 on An. sinensis with emphasis on biology, bionomics, and molecular biology. A total of 538 references were relevant and included. An. sienesis occurs in 29 Chinese provinces. Temperature can affect most life-history parameters. Most An. sinensis are zoophilic, but sometimes they are facultatively anthropophilic. Sporozoite analysis demonstrated An. sinensis efficacy on Plasmodium vivax transmission. An. sinensis was not stringently refractory to P. falciparum under experimental conditions, however, sporozoite was not found in salivary glands of field collected An. sinensis. The literature on An. sienesis biology and bionomics was abundant, but molecular studies, such as gene functions and mechanisms, were limited. Only 12 molecules (genes, proteins or enzymes) have been studied. In addition, there were considerable untapped omics resources for potential vector control tools. Existing information on An. sienesis could serve as a baseline for advanced research on biology, bionomics and genetics relevant to vector control strategies. PMID:28848504

Biology, Bionomics and Molecular Biology of Anopheles sinensis Wiedemann 1828 (Diptera: Culicidae), Main Malaria Vector in China.

PubMed

Feng, Xinyu; Zhang, Shaosen; Huang, Fang; Zhang, Li; Feng, Jun; Xia, Zhigui; Zhou, Hejun; Hu, Wei; Zhou, Shuisen

2017-01-01

China has set a goal to eliminate all malaria in the country by 2020, but it is unclear if current understanding of malaria vectors and transmission is sufficient to achieve this objective. Anopheles sinensis is the most widespread malaria vector specie in China, which is also responsible for vivax malaria outbreak in central China. We reviewed literature from 1954 to 2016 on An. sinensis with emphasis on biology, bionomics, and molecular biology. A total of 538 references were relevant and included. An. sienesis occurs in 29 Chinese provinces. Temperature can affect most life-history parameters. Most An. sinensis are zoophilic, but sometimes they are facultatively anthropophilic. Sporozoite analysis demonstrated An. sinensis efficacy on Plasmodium vivax transmission. An. sinensis was not stringently refractory to P. falciparum under experimental conditions, however, sporozoite was not found in salivary glands of field collected An. sinensis . The literature on An. sienesis biology and bionomics was abundant, but molecular studies, such as gene functions and mechanisms, were limited. Only 12 molecules (genes, proteins or enzymes) have been studied. In addition, there were considerable untapped omics resources for potential vector control tools. Existing information on An. sienesis could serve as a baseline for advanced research on biology, bionomics and genetics relevant to vector control strategies.

Systems biology and mechanics of growth.

PubMed

Eskandari, Mona; Kuhl, Ellen

2015-01-01

In contrast to inert systems, living biological systems have the advantage to adapt to their environment through growth and evolution. This transfiguration is evident during embryonic development, when the predisposed need to grow allows form to follow function. Alterations in the equilibrium state of biological systems breed disease and mutation in response to environmental triggers. The need to characterize the growth of biological systems to better understand these phenomena has motivated the continuum theory of growth and stimulated the development of computational tools in systems biology. Biological growth in development and disease is increasingly studied using the framework of morphoelasticity. Here, we demonstrate the potential for morphoelastic simulations through examples of volume, area, and length growth, inspired by tumor expansion, chronic bronchitis, brain development, intestine formation, plant shape, and myopia. We review the systems biology of living systems in light of biochemical and optical stimuli and classify different types of growth to facilitate the design of growth models for various biological systems within this generic framework. Exploring the systems biology of growth introduces a new venue to control and manipulate embryonic development, disease progression, and clinical intervention. © 2015 Wiley Periodicals, Inc.

Variations in the Biological Functions of HIV-1 Clade C Envelope in a SHIV-Infected Rhesus Macaque during Disease Progression.

PubMed

Tso, For Yue; Abrahamyan, Levon; Hu, Shiu-Lok; Ruprecht, Ruth M; Wood, Charles

2013-01-01

A better understanding of how the biological functions of the HIV-1 envelope (Env) changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection of macaque with SHIV, expressing HIV-1 clade C Env V1-V5 region. By using this model, we examined the changes in biological functions of Env in the infected animal over the entire disease course. Our data showed an increase in the neutralization resistance phenotype over time and coincided with the decrease in the net charges of the V1-V5 region. Infection of PBMC with provirus expressing various Env clones, isolated from the infected animal over time, showed a surprisingly better replicative fitness for viruses expressing the Env from early time point. Biotinylation and ELISA data also indicated a decrease of cell-surface-associated Env and virion-associated gp120 content with disease progression. This decrease did not affect the CD4-binding capability of Env, but were positively correlated with the decrease of Env fusion ability. Interestingly, some of these changes in biological functions reverted to the pre-AIDS level during advance AIDS. These data suggested a dynamic relationship between the Env V1-V5 region with the host immune pressure. The observed changes of biological functions in this setting might reflect and predict those occurring during natural disease progression in human.

The Inactivation Principle: Mathematical Solutions Minimizing the Absolute Work and Biological Implications for the Planning of Arm Movements

PubMed Central

Berret, Bastien; Darlot, Christian; Jean, Frédéric; Pozzo, Thierry; Papaxanthis, Charalambos; Gauthier, Jean Paul

2008-01-01

An important question in the literature focusing on motor control is to determine which laws drive biological limb movements. This question has prompted numerous investigations analyzing arm movements in both humans and monkeys. Many theories assume that among all possible movements the one actually performed satisfies an optimality criterion. In the framework of optimal control theory, a first approach is to choose a cost function and test whether the proposed model fits with experimental data. A second approach (generally considered as the more difficult) is to infer the cost function from behavioral data. The cost proposed here includes a term called the absolute work of forces, reflecting the mechanical energy expenditure. Contrary to most investigations studying optimality principles of arm movements, this model has the particularity of using a cost function that is not smooth. First, a mathematical theory related to both direct and inverse optimal control approaches is presented. The first theoretical result is the Inactivation Principle, according to which minimizing a term similar to the absolute work implies simultaneous inactivation of agonistic and antagonistic muscles acting on a single joint, near the time of peak velocity. The second theoretical result is that, conversely, the presence of non-smoothness in the cost function is a necessary condition for the existence of such inactivation. Second, during an experimental study, participants were asked to perform fast vertical arm movements with one, two, and three degrees of freedom. Observed trajectories, velocity profiles, and final postures were accurately simulated by the model. In accordance, electromyographic signals showed brief simultaneous inactivation of opposing muscles during movements. Thus, assuming that human movements are optimal with respect to a certain integral cost, the minimization of an absolute-work-like cost is supported by experimental observations. Such types of optimality criteria may be applied to a large range of biological movements. PMID:18949023

A lesson for site-selective C-H functionalization on 2-pyridones: radical, organometallic, directing group and steric controls.

PubMed

Hirano, Koji; Miura, Masahiro

2018-01-07

A 2-pyridone ring is a frequently occurring subunit in natural products, biologically active compounds, and pharmaceutical targets. Thus, the selective synthesis of substituted 2-pyridone derivatives through decoration and/or formation of pyridone rings has been one of the important longstanding subjects in organic synthetic chemistry. This minireview focuses on recent advances in site-selective C-H functionalization on 2-pyridone. The reported procedures are categorized according to the site selectivity that is achieved, and the substrate scope, limitations, mechanism, and controlling factors are briefly summarized.

A lesson for site-selective C–H functionalization on 2-pyridones: radical, organometallic, directing group and steric controls

PubMed Central

2017-01-01

A 2-pyridone ring is a frequently occurring subunit in natural products, biologically active compounds, and pharmaceutical targets. Thus, the selective synthesis of substituted 2-pyridone derivatives through decoration and/or formation of pyridone rings has been one of the important longstanding subjects in organic synthetic chemistry. This minireview focuses on recent advances in site-selective C–H functionalization on 2-pyridone. The reported procedures are categorized according to the site selectivity that is achieved, and the substrate scope, limitations, mechanism, and controlling factors are briefly summarized. PMID:29629070

Natural antisense RNAs as mRNA regulatory elements in bacteria: a review on function and applications.

PubMed

Saberi, Fatemeh; Kamali, Mehdi; Najafi, Ali; Yazdanparast, Alavieh; Moghaddam, Mehrdad Moosazadeh

2016-01-01

Naturally occurring antisense RNAs are small, diffusible, untranslated transcripts that pair to target RNAs at specific regions of complementarity to control their biological function by regulating gene expression at the post-transcriptional level. This review focuses on known cases of antisense RNA control in prokaryotes and provides an overview of some natural RNA-based mechanisms that bacteria use to modulate gene expression, such as mRNA sensors, riboswitches and antisense RNAs. We also highlight recent advances in RNA-based technology. The review shows that studies on both natural and synthetic systems are reciprocally beneficial.

The Deterministic Origins of Sexism.

ERIC Educational Resources Information Center

Perry, Melissa J.; Albee, George W.

1998-01-01

Discusses the physical, sexual, and psychological ramifications of biological determinism using examples from the global status of women's health, the continuation of female genital mutilation, and the history of sexist beliefs in psychology that serve a social control function of creating and defining women's psychopathology. (Author/SLD)

Developing PFC Representations Using Reinforcement Learning

ERIC Educational Resources Information Center

Reynolds, Jeremy R.; O'Reilly, Randall C.

2009-01-01

From both functional and biological considerations, it is widely believed that action production, planning, and goal-oriented behaviors supported by the frontal cortex are organized hierarchically [Fuster (1991); Koechlin, E., Ody, C., & Kouneiher, F. (2003). "Neuroscience: The architecture of cognitive control in the human prefrontal cortex."…

Ecological value of soil carbon management

USDA-ARS?s Scientific Manuscript database

Management of soil carbon is critical to the climate change debate, as well as to the long-term productivity and ecosystem resilience of the biosphere. Soil organic carbon is a key ecosystem property that indicates inherent productivity of land, controls soil biological functioning and diversity, r...

Impact of elevated levels of CO2 on animal mediated ecosystem function: the modification of sediment nutrient fluxes by burrowing urchins.

PubMed

Widdicombe, S; Beesley, A; Berge, J A; Dashfield, S L; McNeill, C L; Needham, H R; Øxnevad, S

2013-08-30

A mesocosm experiment was conducted to quantify the relationships between the presence and body size of two burrowing heart urchins (Brissopsis lyrifera and Echinocardium cordatum) and rates of sediment nutrient flux. Furthermore, the impact of seawater acidification on these relationships was determined during this 40-day exposure experiment. Using carbon dioxide (CO2) gas, seawater was acidified to pHNBS 7.6, 7.2 or 6.8. Control treatments were maintained in natural seawater (pH≈8.0). Under normocapnic conditions, burrowing urchins were seen to reduce the sediment uptake of nitrite or nitrate whilst enhancing the release of silicate and phosphate. In acidified (hypercapnic) treatments, the biological control of biogeochemical cycles by urchins was significantly affected, probably through the combined impacts of high CO2 on nitrifying bacteria, benthic algae and urchin behaviour. This study highlights the importance of considering biological interactions when predicting the consequences of seawater acidification on ecosystem function. Copyright © 2012 Elsevier Ltd. All rights reserved.

Bio-Fluid Dynamics in a Centimeter-Scale Diagnostics Incubator with Integrated Perfusion

NASA Astrophysics Data System (ADS)

Vukasinovic, J.; Cullen, D. K.; Glezer, A.; Laplaca, M. C.

2006-11-01

Growing demands for long-term incubation of biologically faithful, three-dimensional neuronal and other cultures during extended physiological studies require efficient perfusion platforms with functional vasculatures that mimic the in vivo condition in a thermally regulated environment. While thermostatically controlled incubation baths with capillary action perfusion are available, their use is confined to specific experimental conditions. The interstitial nutrient and gas delivery remains diffusion limited over the long term and cultures decay metabolically. To overcome these problems, we describe simple fabrication and experimental characterization of a compact, diagnostics incubator that allows in situ monitoring of culture activity with a superior control of critical biological functions using convectively enhanced heat and mass transport. To overcome intercellular diffusion barriers culture is exposed to a direct flow of media issuing from an array of micro-nozzles that are directed normal to the substrate upholding the culture, and further improved by 3-D convection induced by jet interactions and biased, peripheral perfusate extraction through an array of microchannels as demonstrated by microPIV measurements.

Effects of microgravity or simulated launch on testicular function in rats

NASA Technical Reports Server (NTRS)

Amann, R. P.; Deaver, D. R.; Zirkin, B. R.; Grills, G. S.; Sapp, W. J.; Veeramachaneni, D. N. R.; Clemens, J. W.; Banerjee, S. D.; Folmer, J.; Gruppi, C. M.

1992-01-01

Reproductive toxicology and cellular and molecular biology approaches were used to evaluate testicular function in rats from Cosmos 2044. It is found that concentrations of testosterone in testicular tissue or peripheral blood plasma were reduced in flight rates to less than 20 percent of values for simulated-launch or vivarium controls. Spermatogenesis was essentially normal in flight rats, but production of testosterone was severely depressed.

Functional mesoporous silica nanoparticles for bio-imaging applications.

PubMed

Cha, Bong Geun; Kim, Jaeyun

2018-03-22

Biomedical investigations using mesoporous silica nanoparticles (MSNs) have received significant attention because of their unique properties including controllable mesoporous structure, high specific surface area, large pore volume, and tunable particle size. These unique features make MSNs suitable for simultaneous diagnosis and therapy with unique advantages to encapsulate and load a variety of therapeutic agents, deliver these agents to the desired location, and release the drugs in a controlled manner. Among various clinical areas, nanomaterials-based bio-imaging techniques have advanced rapidly with the development of diverse functional nanoparticles. Due to the unique features of MSNs, an imaging agent supported by MSNs can be a promising system for developing targeted bio-imaging contrast agents with high structural stability and enhanced functionality that enable imaging of various modalities. Here, we review the recent achievements on the development of functional MSNs for bio-imaging applications, including optical imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), ultrasound imaging, and multimodal imaging for early diagnosis. With further improvement in noninvasive bio-imaging techniques, the MSN-supported imaging agent systems are expected to contribute to clinical applications in the future. This article is categorized under: Diagnostic Tools > In vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology. © 2018 Wiley Periodicals, Inc.

The Protein Interactome of Mycobacteriophage Giles Predicts Functions for Unknown Proteins.

PubMed

Mehla, Jitender; Dedrick, Rebekah M; Caufield, J Harry; Siefring, Rachel; Mair, Megan; Johnson, Allison; Hatfull, Graham F; Uetz, Peter

2015-08-01

Mycobacteriophages are viruses that infect mycobacterial hosts and are prevalent in the environment. Nearly 700 mycobacteriophage genomes have been completely sequenced, revealing considerable diversity and genetic novelty. Here, we have determined the protein complement of mycobacteriophage Giles by mass spectrometry and mapped its genome-wide protein interactome to help elucidate the roles of its 77 predicted proteins, 50% of which have no known function. About 22,000 individual yeast two-hybrid (Y2H) tests with four different Y2H vectors, followed by filtering and retest screens, resulted in 324 reproducible protein-protein interactions, including 171 (136 nonredundant) high-confidence interactions. The complete set of high-confidence interactions among Giles proteins reveals new mechanistic details and predicts functions for unknown proteins. The Giles interactome is the first for any mycobacteriophage and one of just five known phage interactomes so far. Our results will help in understanding mycobacteriophage biology and aid in development of new genetic and therapeutic tools to understand Mycobacterium tuberculosis. Mycobacterium tuberculosis causes over 9 million new cases of tuberculosis each year. Mycobacteriophages, viruses of mycobacterial hosts, hold considerable potential to understand phage diversity, evolution, and mycobacterial biology, aiding in the development of therapeutic tools to control mycobacterial infections. The mycobacteriophage Giles protein-protein interaction network allows us to predict functions for unknown proteins and shed light on major biological processes in phage biology. For example, Giles gp76, a protein of unknown function, is found to associate with phage packaging and maturation. The functions of mycobacteriophage-derived proteins may suggest novel therapeutic approaches for tuberculosis. Our ORFeome clone set of Giles proteins and the interactome data will be useful resources for phage interactomics. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Hierarchically structured transparent hybrid membranes by in situ growth of mesostructured organosilica in host polymer

NASA Astrophysics Data System (ADS)

Vallé, Karine; Belleville, Philippe; Pereira, Franck; Sanchez, Clément

2006-02-01

The elaborate performances characterizing natural materials result from functional hierarchical constructions at scales ranging from nanometres to millimetres, each construction allowing the material to fit the physical or chemical demands occurring at these different levels. Hierarchically structured materials start to demonstrate a high input in numerous promising applied domains such as sensors, catalysis, optics, fuel cells, smart biologic and cosmetic vectors. In particular, hierarchical hybrid materials permit the accommodation of a maximum of elementary functions in a small volume, thereby optimizing complementary possibilities and properties between inorganic and organic components. The reported strategies combine sol-gel chemistry, self-assembly routes using templates that tune the material's architecture and texture with the use of larger inorganic, organic or biological templates such as latex, organogelator-derived fibres, nanolithographic techniques or controlled phase separation. We propose an approach to forming transparent hierarchical hybrid functionalized membranes using in situ generation of mesostructured hybrid phases inside a non-porogenic hydrophobic polymeric host matrix. We demonstrate that the control of the multiple affinities existing between organic and inorganic components allows us to design the length-scale partitioning of hybrid nanomaterials with tuned functionalities and desirable size organization from ångström to centimetre. After functionalization of the mesoporous hybrid silica component, the resulting membranes have good ionic conductivity offering interesting perspectives for the design of solid electrolytes, fuel cells and other ion-transport microdevices.

Using spatial information about recurrence risk for robust optimization of dose-painting prescription functions

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

Bender, Edward T.

Purpose: To develop a robust method for deriving dose-painting prescription functions using spatial information about the risk for disease recurrence. Methods: Spatial distributions of radiobiological model parameters are derived from distributions of recurrence risk after uniform irradiation. These model parameters are then used to derive optimal dose-painting prescription functions given a constant mean biologically effective dose. Results: An estimate for the optimal dose distribution can be derived based on spatial information about recurrence risk. Dose painting based on imaging markers that are moderately or poorly correlated with recurrence risk are predicted to potentially result in inferior disease control when comparedmore » the same mean biologically effective dose delivered uniformly. A robust optimization approach may partially mitigate this issue. Conclusions: The methods described here can be used to derive an estimate for a robust, patient-specific prescription function for use in dose painting. Two approximate scaling relationships were observed: First, the optimal choice for the maximum dose differential when using either a linear or two-compartment prescription function is proportional to R, where R is the Pearson correlation coefficient between a given imaging marker and recurrence risk after uniform irradiation. Second, the predicted maximum possible gain in tumor control probability for any robust optimization technique is nearly proportional to the square of R.« less

Monotonicity of fitness landscapes and mutation rate control.

PubMed

Belavkin, Roman V; Channon, Alastair; Aston, Elizabeth; Aston, John; Krašovec, Rok; Knight, Christopher G

2016-12-01

A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the performance of evolutionary algorithms. Much biological theory in this area is based on Ronald Fisher's work, who used Euclidean geometry to study the relation between mutation size and expected fitness of the offspring in infinite phenotypic spaces. Here we reconsider this theory based on the alternative geometry of discrete and finite spaces of DNA sequences. First, we consider the geometric case of fitness being isomorphic to distance from an optimum, and show how problems of optimal mutation rate control can be solved exactly or approximately depending on additional constraints of the problem. Then we consider the general case of fitness communicating only partial information about the distance. We define weak monotonicity of fitness landscapes and prove that this property holds in all landscapes that are continuous and open at the optimum. This theoretical result motivates our hypothesis that optimal mutation rate functions in such landscapes will increase when fitness decreases in some neighbourhood of an optimum, resembling the control functions derived in the geometric case. We test this hypothesis experimentally by analysing approximately optimal mutation rate control functions in 115 complete landscapes of binding scores between DNA sequences and transcription factors. Our findings support the hypothesis and find that the increase of mutation rate is more rapid in landscapes that are less monotonic (more rugged). We discuss the relevance of these findings to living organisms.

Advances in the application of genetic manipulation methods to apicomplexan parasites.

PubMed

Suarez, C E; Bishop, R P; Alzan, H F; Poole, W A; Cooke, B M

2017-10-01

Apicomplexan parasites such as Babesia, Theileria, Eimeria, Cryptosporidium and Toxoplasma greatly impact animal health globally, and improved, cost-effective measures to control them are urgently required. These parasites have complex multi-stage life cycles including obligate intracellular stages. Major gaps in our understanding of the biology of these relatively poorly characterised parasites and the diseases they cause severely limit options for designing novel control methods. Here we review potentially important shared aspects of the biology of these parasites, such as cell invasion, host cell modification, and asexual and sexual reproduction, and explore the potential of the application of relatively well-established or newly emerging genetic manipulation methods, such as classical transfection or gene editing, respectively, for closing important gaps in our knowledge of the function of specific genes and proteins, and the biology of these parasites. In addition, genetic manipulation methods impact the development of novel methods of control of the diseases caused by these economically important parasites. Transient and stable transfection methods, in conjunction with whole and deep genome sequencing, were initially instrumental in improving our understanding of the molecular biology of apicomplexan parasites and paved the way for the application of the more recently developed gene editing methods. The increasingly efficient and more recently developed gene editing methods, in particular those based on the CRISPR/Cas9 system and previous conceptually similar techniques, are already contributing to additional gene function discovery using reverse genetics and related approaches. However, gene editing methods are only possible due to the increasing availability of in vitro culture, transfection, and genome sequencing and analysis techniques. We envisage that rapid progress in the development of novel gene editing techniques applied to apicomplexan parasites of veterinary interest will ultimately lead to the development of novel and more efficient methods for disease control. Published by Elsevier Ltd.

In silico evolution of the hunchback gene indicates redundancy in cis-regulatory organization and spatial gene expression

PubMed Central

Zagrijchuk, Elizaveta A.; Sabirov, Marat A.; Holloway, David M.; Spirov, Alexander V.

2014-01-01

Biological development depends on the coordinated expression of genes in time and space. Developmental genes have extensive cis-regulatory regions which control their expression. These regions are organized in a modular manner, with different modules controlling expression at different times and locations. Both how modularity evolved and what function it serves are open questions. We present a computational model for the cis-regulation of the hunchback (hb) gene in the fruit fly (Drosophila). We simulate evolution (using an evolutionary computation approach from computer science) to find the optimal cis-regulatory arrangements for fitting experimental hb expression patterns. We find that the cis-regulatory region tends to readily evolve modularity. These cis-regulatory modules (CRMs) do not tend to control single spatial domains, but show a multi-CRM/multi-domain correspondence. We find that the CRM-domain correspondence seen in Drosophila evolves with a high probability in our model, supporting the biological relevance of the approach. The partial redundancy resulting from multi-CRM control may confer some biological robustness against corruption of regulatory sequences. The technique developed on hb could readily be applied to other multi-CRM developmental genes. PMID:24712536

Functional Cellular Mimics for the Spatiotemporal Control of Multiple Enzymatic Cascade Reactions.

PubMed

Liu, Xiaoling; Formanek, Petr; Voit, Brigitte; Appelhans, Dietmar

2017-12-18

Next-generation therapeutic approaches are expected to rely on the engineering of biomimetic cellular systems that can mimic specific cellular functions. Herein, we demonstrate a highly effective route for constructing structural and functional eukaryotic cell mimics by loading pH-sensitive polymersomes as membrane-associated and free-floating organelle mimics inside the multifunctional cell membrane. Metabolism mimicry has been validated by performing successive enzymatic cascade reactions spatially separated at specific sites of cell mimics in the presence and absence of extracellular organelle mimics. These enzymatic reactions take place in a highly controllable, reproducible, efficient, and successive manner. Our biomimetic approach to material design for establishing functional principles brings considerable enrichment to the fields of biomedicine, biocatalysis, biotechnology, and systems biology. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analyzing and Understanding Lipids of Yeast: A Challenging Endeavor.

PubMed

Kohlwein, Sepp D

2017-05-01

Lipids are essential biomolecules with diverse biological functions, ranging from building blocks for all biological membranes to energy substrates, signaling molecules, and protein modifiers. Despite advances in lipid analytics by mass spectrometry, the extraction and quantitative analysis of the diverse classes of lipids are still an experimental challenge. Yeast is a model organism that provides several advantages for studying lipid metabolism, because most biosynthetic pathways are well described and a great deal of information is available on the regulatory mechanisms that control lipid homeostasis. In addition, the composition of yeast lipids is much less complex than that of mammalian lipids, making yeast an excellent reference system for studying lipid-associated cell functions. © 2017 Cold Spring Harbor Laboratory Press.

Cell biology of spinocerebellar ataxia

PubMed Central

2012-01-01

Ataxia is a neurological disorder characterized by loss of control of body movements. Spinocerebellar ataxia (SCA), previously known as autosomal dominant cerebellar ataxia, is a biologically robust group of close to 30 progressive neurodegenerative diseases. Six SCAs, including the more prevalent SCA1, SCA2, SCA3, and SCA6 along with SCA7 and SCA17 are caused by expansion of a CAG repeat that encodes a polyglutamine tract in the affected protein. How the mutated proteins in these polyglutamine SCAs cause disease is highly debated. Recent work suggests that the mutated protein contributes to pathogenesis within the context of its “normal” cellular function. Thus, understanding the cellular function of these proteins could aid in the development of therapeutics. PMID:22508507

Neuronal Organization of Deep Brain Opsin Photoreceptors in Adult Teleosts

PubMed Central

Hang, Chong Yee; Kitahashi, Takashi; Parhar, Ishwar S.

2016-01-01

Biological impacts of light beyond vision, i.e., non-visual functions of light, signify the need to better understand light detection (or photoreception) systems in vertebrates. Photopigments, which comprise light-absorbing chromophores bound to a variety of G-protein coupled receptor opsins, are responsible for visual and non-visual photoreception. Non-visual opsin photopigments in the retina of mammals and extra-retinal tissues of non-mammals play an important role in non-image-forming functions of light, e.g., biological rhythms and seasonal reproduction. This review highlights the role of opsin photoreceptors in the deep brain, which could involve conserved neurochemical systems that control different time- and light-dependent physiologies in in non-mammalian vertebrates including teleost fish. PMID:27199680

Paradoxical roles of dual oxidases in cancer biology.

PubMed

Little, Andrew C; Sulovari, Arvis; Danyal, Karamatullah; Heppner, David E; Seward, David J; van der Vliet, Albert

2017-09-01

Dysregulated oxidative metabolism is a well-recognized aspect of cancer biology, and many therapeutic strategies are based on targeting cancers by altering cellular redox pathways. The NADPH oxidases (NOXes) present an important enzymatic source of biological oxidants, and the expression and activation of several NOX isoforms are frequently dysregulated in many cancers. Cell-based studies have demonstrated a role for several NOX isozymes in controlling cell proliferation and/or cell migration, further supporting a potential contributing role for NOX in promoting cancer. While various NOX isoforms are often upregulated in cancers, paradoxical recent findings indicate that dual oxidases (DUOXes), normally prominently expressed in epithelial lineages, are frequently suppressed in epithelial-derived cancers by epigenetic mechanisms, although the functional relevance of such DUOX silencing has remained unclear. This review will briefly summarize our current understanding regarding the importance of reactive oxygen species (ROS) and NOXes in cancer biology, and focus on recent observations indicating the unique and seemingly opposing roles of DUOX enzymes in cancer biology. We will discuss current knowledge regarding the functional properties of DUOX, and recent studies highlighting mechanistic consequences of DUOX1 loss in lung cancer, and its consequences for tumor invasiveness and current anticancer therapy. Finally, we will also discuss potentially unique roles for the DUOX maturation factors. Overall, a better understanding of mechanisms that regulate DUOX and the functional consequences of DUOX silencing in cancer may offer valuable new diagnostic insights and novel therapeutic opportunities. Copyright © 2017 Elsevier Inc. All rights reserved.

Mammalian skin cell biology: at the interface between laboratory and clinic.

PubMed

Watt, Fiona M

2014-11-21

Mammalian skin research represents the convergence of three complementary disciplines: cell biology, mouse genetics, and dermatology. The skin provides a paradigm for current research in cell adhesion, inflammation, and tissue stem cells. Here, I discuss recent insights into the cell biology of skin. Single-cell analysis has revealed that human epidermal stem cells are heterogeneous and differentiate in response to multiple extrinsic signals. Live-cell imaging, optogenetics, and cell ablation experiments show skin cells to be remarkably dynamic. High-throughput, genome-wide approaches have yielded unprecedented insights into the circuitry that controls epidermal stem cell fate. Last, integrative biological analysis of human skin disorders has revealed unexpected functions for elements of the skin that were previously considered purely structural. Copyright © 2014, American Association for the Advancement of Science.

The phytotronist and the phenotype: plant physiology, Big Science, and a Cold War biology of the whole plant.

PubMed

Munns, David P D

2015-04-01

This paper describes how, from the early twentieth century, and especially in the early Cold War era, the plant physiologists considered their discipline ideally suited among all the plant sciences to study and explain biological functions and processes, and ranked their discipline among the dominant forms of the biological sciences. At their apex in the late-1960s, the plant physiologists laid claim to having discovered nothing less than the "basic laws of physiology." This paper unwraps that claim, showing that it emerged from the construction of monumental big science laboratories known as phytotrons that gave control over the growing environment. Control meant that plant physiologists claimed to be able to produce a standard phenotype valid for experimental biology. Invoking the standards of the physical sciences, the plant physiologists heralded basic biological science from the phytotronic produced phenotype. In the context of the Cold War era, the ability to pursue basic science represented the highest pinnacle of standing within the scientific community. More broadly, I suggest that by recovering the history of an underappreciated discipline, plant physiology, and by establishing the centrality of the story of the plant sciences in the history of biology can historians understand the massive changes wrought to biology by the conceptual emergence of the molecular understanding of life, the dominance of the discipline of molecular biology, and the rise of biotechnology in the 1980s. Copyright © 2015 Elsevier Ltd. All rights reserved.

Morphology-Controlled Synthesis of Rhodium Nanoparticles for Cancer Phototherapy.

PubMed

Kang, Seounghun; Shin, Woojun; Choi, Myung-Ho; Ahn, Minchul; Kim, Young-Kwan; Kim, Seongchan; Min, Dal-Hee; Jang, Hongje

2018-06-22

Rhodium nanoparticles are promising transition metal nanocatalysts for electrochemical and synthetic organic chemistry applications. However, notwithstanding their potential, to date, Rh nanoparticles have not been utilized for biological applications; there has been no cytotoxicity study of Rh reported in the literature. In this regard, the absence of a facile and controllable synthetic strategy of Rh nanostructures with various sizes and morphologies might be responsible for the lack of progress in this field. Herein, we have developed a synthetic strategy for Rh nanostructures with controllable morphology through an inverse-directional galvanic replacement reaction. Three types of Rh-based nanostructures-nanoshells, nanoframes, and porous nanoplates-were successfully synthesized. A plausible synthetic mechanism based on thermodynamic considerations has also been proposed. The cytotoxicity, surface functionalization, and photothermal therapeutic effect of manufactured Rh nanostructures were systematically investigated to reveal their potential for in vitro and in vivo biological applications. Considering the comparable behavior of porous Rh nanoplates to that of gold nanostructures that are widely used in nanomedicine, the present study introduces Rh-based nanostructures into the field of biological research.

An overview of Japanese CELSS research activities

NASA Technical Reports Server (NTRS)

Nitta, Keiji

1987-01-01

Development of Controlled Ecological Life Support System (CELSS) technology is inevitable for future long duration stays of human beings in space, for lunar base construction and for manned Mars flight programs. CELSS functions can be divided into 2 categories, Environmental Control and Material Recycling. Temperature, humidity, total atmospheric pressure and partial pressure of oxygen and carbon dioxide, necessary for all living things, are to be controlled by the environment control function. This function can be performed by technologies already developed and used as the Environment Control Life Support System (ECLSS) of Space Shuttle and Space Station. As for material recycling, matured technologies have not yet been established for fully satisfying the specific metabolic requirements of each living thing including human beings. Therefore, research activities for establishing CELSS technology should be focused on material recycling technologies using biological systems such as plants and animals and physico-chemical systems, for example, a gas recycling system, a water purifying and recycling system and a waste management system. Japanese research activities were conducted and will be continued accordingly.

Control of electrochemical signals from quantum dots conjugated to organic materials by using DNA structure in an analog logic gate.

PubMed

Chen, Qi; Yoo, Si-Youl; Chung, Yong-Ho; Lee, Ji-Young; Min, Junhong; Choi, Jeong-Woo

2016-10-01

Various bio-logic gates have been studied intensively to overcome the rigidity of single-function silicon-based logic devices arising from combinations of various gates. Here, a simple control tool using electrochemical signals from quantum dots (QDs) was constructed using DNA and organic materials for multiple logic functions. The electrochemical redox current generated from QDs was controlled by the DNA structure. DNA structure, in turn, was dependent on the components (organic materials) and the input signal (pH). Independent electrochemical signals from two different logic units containing QDs were merged into a single analog-type logic gate, which was controlled by two inputs. We applied this electrochemical biodevice to a simple logic system and achieved various logic functions from the controlled pH input sets. This could be further improved by choosing QDs, ionic conditions, or DNA sequences. This research provides a feasible method for fabricating an artificial intelligence system. Copyright © 2016 Elsevier B.V. All rights reserved.

Integration of Plant Defense Traits with Biological Control of Arthropod Pests: Challenges and Opportunities

PubMed Central

Peterson, Julie A.; Ode, Paul J.; Oliveira-Hofman, Camila; Harwood, James D.

2016-01-01

Crop plants exhibit a wide diversity of defensive traits and strategies to protect themselves from damage by herbivorous pests and disease. These defensive traits may be naturally occurring or artificially selected through crop breeding, including introduction via genetic engineering. While these traits can have obvious and direct impacts on herbivorous pests, many have profound effects on higher trophic levels, including the natural enemies of herbivores. Multi-trophic effects of host plant resistance have the potential to influence, both positively and negatively, biological control. Plant defense traits can influence both the numerical and functional responses of natural enemies; these interactions can be semiochemically, plant toxin-, plant nutrient-, and/or physically mediated. Case studies involving predators, parasitoids, and pathogens of crop pests will be presented and discussed. These diverse groups of natural enemies may respond differently to crop plant traits based on their own unique biology and the ecological niches they fill. Genetically modified crop plants that have been engineered to express transgenic products affecting herbivorous pests are an additional consideration. For the most part, transgenic plant incorporated protectant (PIP) traits are compatible with biological control due to their selective toxicity to targeted pests and relatively low non-target impacts, although transgenic crops may have indirect effects on higher trophic levels and arthropod communities mediated by lower host or prey number and/or quality. Host plant resistance and biological control are two of the key pillars of integrated pest management; their potential interactions, whether they are synergistic, complementary, or disruptive, are key in understanding and achieving sustainable and effective pest management. PMID:27965695

Integration of Plant Defense Traits with Biological Control of Arthropod Pests: Challenges and Opportunities.

PubMed

Peterson, Julie A; Ode, Paul J; Oliveira-Hofman, Camila; Harwood, James D

2016-01-01

Crop plants exhibit a wide diversity of defensive traits and strategies to protect themselves from damage by herbivorous pests and disease. These defensive traits may be naturally occurring or artificially selected through crop breeding, including introduction via genetic engineering. While these traits can have obvious and direct impacts on herbivorous pests, many have profound effects on higher trophic levels, including the natural enemies of herbivores. Multi-trophic effects of host plant resistance have the potential to influence, both positively and negatively, biological control. Plant defense traits can influence both the numerical and functional responses of natural enemies; these interactions can be semiochemically, plant toxin-, plant nutrient-, and/or physically mediated. Case studies involving predators, parasitoids, and pathogens of crop pests will be presented and discussed. These diverse groups of natural enemies may respond differently to crop plant traits based on their own unique biology and the ecological niches they fill. Genetically modified crop plants that have been engineered to express transgenic products affecting herbivorous pests are an additional consideration. For the most part, transgenic plant incorporated protectant (PIP) traits are compatible with biological control due to their selective toxicity to targeted pests and relatively low non-target impacts, although transgenic crops may have indirect effects on higher trophic levels and arthropod communities mediated by lower host or prey number and/or quality. Host plant resistance and biological control are two of the key pillars of integrated pest management; their potential interactions, whether they are synergistic, complementary, or disruptive, are key in understanding and achieving sustainable and effective pest management.

Synthetic Biology of Polyhydroxyalkanoates (PHA).

PubMed

Meng, De-Chuan; Chen, Guo-Qiang

Microbial polyhydroxyalkanoates (PHA) are a family of biodegradable and biocompatible polyesters which have been extensively studied using synthetic biology and metabolic engineering methods for improving production and for widening its diversity. Synthetic biology has allowed PHA to become composition controllable random copolymers, homopolymers, and block copolymers. Recent developments showed that it is possible to establish a microbial platform for producing not only random copolymers with controllable monomers and their ratios but also structurally defined homopolymers and block copolymers. This was achieved by engineering the genome of Pseudomonas putida or Pseudomonas entomophiles to weaken the β-oxidation and in situ fatty acid synthesis pathways, so that a fatty acid fed to the bacteria maintains its original chain length and structures when incorporated into the PHA chains. The engineered bacterium allows functional groups in a fatty acid to be introduced into PHA, forming functional PHA, which, upon grafting, generates endless PHA variety. Recombinant Escherichia coli also succeeded in producing efficiently poly(3-hydroxypropionate) or P3HP, the strongest member of PHA. Synthesis pathways of P3HP and its copolymer P3HB3HP of 3-hydroxybutyrate and 3-hydroxypropionate were assembled respectively to allow their synthesis from glucose. CRISPRi was also successfully used to manipulate simultaneously multiple genes and control metabolic flux in E. coli to obtain a series of copolymer P3HB4HB of 3-hydroxybutyrate (3HB) and 4-hydroxybutyrate (4HB). The bacterial shapes were successfully engineered for enhanced PHA accumulation.

Common features in diverse insect clocks.

PubMed

Numata, Hideharu; Miyazaki, Yosuke; Ikeno, Tomoko

2015-01-01

This review describes common features among diverse biological clocks in insects, including circadian, circatidal, circalunar/circasemilunar, and circannual clocks. These clocks control various behaviors, physiological functions, and developmental events, enabling adaptation to periodic environmental changes. Circadian clocks also function in time-compensation for celestial navigation and in the measurement of day or night length for photoperiodism. Phase response curves for such clocks reported thus far exhibit close similarities; specifically, the circannual clock in Anthrenus verbasci shows striking similarity to circadian clocks in its phase response. It is suggested that diverse biological clocks share physiological properties in their phase responses irrespective of period length. Molecular and physiological mechanisms are best understood for the optic-lobe and mid-brain circadian clocks, although there is no direct evidence that these clocks are involved in rhythmic phenomena other than circadian rhythms in daily events. Circadian clocks have also been localized in peripheral tissues, and research on their role in various rhythmic phenomena has been started. Although clock genes have been identified as controllers of circadian rhythms in daily events, some of these genes have also been shown to be involved in photoperiodism and possibly in time-compensated celestial navigation. In contrast, there is no experimental evidence indicating that any known clock gene is involved in biological clocks other than circadian clocks.

Droplet interface bilayer reconstitution and activity measurement of the mechanosensitive channel of large conductance from Escherichia coli.

PubMed

Barriga, Hanna M G; Booth, Paula; Haylock, Stuart; Bazin, Richard; Templer, Richard H; Ces, Oscar

2014-09-06

Droplet interface bilayers (DIBs) provide an exciting new platform for the study of membrane proteins in stable bilayers of controlled composition. To date, the successful reconstitution and activity measurement of membrane proteins in DIBs has relied on the use of the synthetic lipid 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC). We report the functional reconstitution of the mechanosensitive channel of large conductance (MscL) into DIBs composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), a lipid of significantly greater biological relevance than DPhPC. MscL functionality has been demonstrated using a fluorescence-based assay, showing that dye flow occurs across the DIB when MscL is gated by the cysteine reactive chemical 2-(trimethylammonium)ethyl methane thiosulfonate bromide (MTSET). MscL has already been the subject of a number of studies investigating its interaction with the membrane. We propose that this method will pave the way for future MscL studies looking in detail at the effects of controlled composition or membrane asymmetry on MscL activity using biologically relevant lipids and will also be applicable to other lipid-protein systems, paving the way for the study of membrane proteins in DIBs with biologically relevant lipids.

Chemical copatterning strategies using azlactone-based block copolymers

DOE PAGES

Masigol, Mohammadali; Barua, Niloy; Retterer, Scott T.; ...

2017-09-01

Interfaces can be modified with azlactone-functional polymers in order to manipulate the chemical surface reactivity. Azlactone groups are highly reactive toward amine, thiol, and alcohol nucleophiles, providing a versatile coupling chemistry for secondary surface modification. Azlactone-based surface polymers have been explored in numerous applications, including chemical and biological capture, sensing, and cell culture. These applications often require that the polymer is copatterned within a chemically or biologically inert background; however, common fabrication methods degrade azlactone groups during processing steps or result in polymer films with poorly controlled thicknesses. Here, the authors develop fabrication strategies using parylene lift-off and interface-directed assemblymore » methods to generate microscale patterns of azlactone-based block copolymer in chemically or biologically inert backgrounds. The functionality of azlactone groups was preserved during fabrication, and patterned films appeared as uniform, 80–120nm brushlike films. The authors also develop a patterning approach that uses a novel microcontact stamping method to generate cross-linked, three-dimensional structures of azlactone-based polymers with controllable, microscale thicknesses. The authors identify the benefits of each approach and expect these polymers and patterning strategies to provide a versatile toolbox for developing synthetic interfaces with tuned chemical and physical features for sensing, cell culture, or material capture applications.« less

Chemical copatterning strategies using azlactone-based block copolymers

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

Masigol, Mohammadali; Barua, Niloy; Retterer, Scott T.

Interfaces can be modified with azlactone-functional polymers in order to manipulate the chemical surface reactivity. Azlactone groups are highly reactive toward amine, thiol, and alcohol nucleophiles, providing a versatile coupling chemistry for secondary surface modification. Azlactone-based surface polymers have been explored in numerous applications, including chemical and biological capture, sensing, and cell culture. These applications often require that the polymer is copatterned within a chemically or biologically inert background; however, common fabrication methods degrade azlactone groups during processing steps or result in polymer films with poorly controlled thicknesses. Here, the authors develop fabrication strategies using parylene lift-off and interface-directed assemblymore » methods to generate microscale patterns of azlactone-based block copolymer in chemically or biologically inert backgrounds. The functionality of azlactone groups was preserved during fabrication, and patterned films appeared as uniform, 80–120nm brushlike films. The authors also develop a patterning approach that uses a novel microcontact stamping method to generate cross-linked, three-dimensional structures of azlactone-based polymers with controllable, microscale thicknesses. The authors identify the benefits of each approach and expect these polymers and patterning strategies to provide a versatile toolbox for developing synthetic interfaces with tuned chemical and physical features for sensing, cell culture, or material capture applications.« less

Feedback regulation of TGF-β signaling.

PubMed

Yan, Xiaohua; Xiong, Xiangyang; Chen, Ye-Guang

2018-01-01

Transforming growth factor beta (TGF-β) is a multi-functional polypeptide that plays a critical role in regulating a broad range of cellular functions and physiological processes. Signaling is initiated when TGF-β ligands bind to two types of cell membrane receptors with intrinsic Ser/Thr kinase activity and transmitted by the intracellular Smad proteins, which act as transcription factors to regulate gene expression in the nucleus. Although it is relatively simple and straight-forward, this TGF-β/Smad pathway is regulated by various feedback loops at different levels, including the ligand, the receptor, Smads and transcription, and is thus fine-tuned in terms of signaling robustness, duration, specificity, and plasticity. The precise control gives rise to versatile and context-dependent pathophysiological functions. In this review, we firstly give an overview of TGF-β signaling, and then discuss how each step of TGF-β signaling is finely controlled by distinct modes of feedback mechanisms, involving both protein regulators and miRNAs. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

ACTH Action on StAR Biology

PubMed Central

Clark, Barbara J.

2016-01-01

Adrenocorticotropin hormone (ACTH) produced by the anterior pituitary stimulates glucocorticoid synthesis by the adrenal cortex. The first step in glucocorticoid synthesis is the delivery of cholesterol to the mitochondrial matrix where the first enzymatic reaction in the steroid hormone biosynthetic pathway occurs. A key response of adrenal cells to ACTH is activation of the cAMP-protein kinase A (PKA) signaling pathway. PKA activation results in an acute increase in expression and function of the Steroidogenic Acute Regulatory protein (StAR). StAR plays an essential role in steroidogenesis- it controls the hormone-dependent movement of cholesterol across the mitochondrial membranes. Currently StAR's mechanism of action remains a major unanswered question in the field. However, some insight may be gained from understanding the mechanism(s) controlling the PKA-dependent phosphorylation of StAR at S194/195 (mouse/human StAR), a modification that is required for function. This mini-review provides a background on StAR's biology with a focus on StAR phosphorylation. The model for StAR translation and phosphorylation at the outer mitochondrial membrane, the location for StAR function, is presented to highlight a unifying theme emerging from diverse studies. PMID:27999527

ACTH Action on StAR Biology.

PubMed

Clark, Barbara J

2016-01-01

Adrenocorticotropin hormone (ACTH) produced by the anterior pituitary stimulates glucocorticoid synthesis by the adrenal cortex. The first step in glucocorticoid synthesis is the delivery of cholesterol to the mitochondrial matrix where the first enzymatic reaction in the steroid hormone biosynthetic pathway occurs. A key response of adrenal cells to ACTH is activation of the cAMP-protein kinase A (PKA) signaling pathway. PKA activation results in an acute increase in expression and function of the Steroidogenic Acute Regulatory protein (StAR). StAR plays an essential role in steroidogenesis- it controls the hormone-dependent movement of cholesterol across the mitochondrial membranes. Currently StAR's mechanism of action remains a major unanswered question in the field. However, some insight may be gained from understanding the mechanism(s) controlling the PKA-dependent phosphorylation of StAR at S194/195 (mouse/human StAR), a modification that is required for function. This mini-review provides a background on StAR's biology with a focus on StAR phosphorylation. The model for StAR translation and phosphorylation at the outer mitochondrial membrane, the location for StAR function, is presented to highlight a unifying theme emerging from diverse studies.

Developing PFC representations using reinforcement learning.

PubMed

Reynolds, Jeremy R; O'Reilly, Randall C

2009-12-01

From both functional and biological considerations, it is widely believed that action production, planning, and goal-oriented behaviors supported by the frontal cortex are organized hierarchically [Fuster (1991); Koechlin, E., Ody, C., & Kouneiher, F. (2003). Neuroscience: The architecture of cognitive control in the human prefrontal cortex. Science, 424, 1181-1184; Miller, G. A., Galanter, E., & Pribram, K. H. (1960). Plans and the structure of behavior. New York: Holt]. However, the nature of the different levels of the hierarchy remains unclear, and little attention has been paid to the origins of such a hierarchy. We address these issues through biologically-inspired computational models that develop representations through reinforcement learning. We explore several different factors in these models that might plausibly give rise to a hierarchical organization of representations within the PFC, including an initial connectivity hierarchy within PFC, a hierarchical set of connections between PFC and subcortical structures controlling it, and differential synaptic plasticity schedules. Simulation results indicate that architectural constraints contribute to the segregation of different types of representations, and that this segregation facilitates learning. These findings are consistent with the idea that there is a functional hierarchy in PFC, as captured in our earlier computational models of PFC function and a growing body of empirical data.

Plant species modifies the functional response of Phytoseiulus persimilis (Acari: Phytoseiidae) to Tetranychus urticae (Acari: Tetranychidae): implications for biological control.

PubMed

Skirvin, D J; Fenlon, J S

2001-02-01

The functional response of the predatory mite Phytoseiulus persimilis Athias-Henriot to eggs of its prey, the spider mite Tetranychus urticae Koch was examined on three plant species. Experiments were done to determine whether differences in the functional response on the three plant species were due to the morphological features of the crop directly on the predator or through an effect of the plant species on the prey. The results show that crop morphology is the only factor influencing the predatory ability of P. persimilis on the three plant species. Fewer eggs were eaten on Ceanothus thyrsiflorus var. 'Autumnal Blue', the plant species with hairy leaves, and greater numbers of prey consumed on Choisya ternata, a species with smooth leaves. However, similarly few eggs were eaten on the smooth, but waxy leaved Euonymus japonicus as on Ceanothus thyrsiflorus, demonstrating that morphological characters of leaves other than the possession of hairs and trichomes may affect the rates of predation. The implications of these results for the tritrophic interactions between plant, predator and prey, and the development of suitable biological control strategies are discussed.

A biomimetic colorimetric logic gate system based on multi-functional peptide-mediated gold nanoparticle assembly

NASA Astrophysics Data System (ADS)

Li, Yong; Li, Wang; He, Kai-Yu; Li, Pei; Huang, Yan; Nie, Zhou; Yao, Shou-Zhuo

2016-04-01

In natural biological systems, proteins exploit various functional peptide motifs to exert target response and activity switch, providing a functional and logic basis for complex cellular activities. Building biomimetic peptide-based bio-logic systems is highly intriguing but remains relatively unexplored due to limited logic recognition elements and complex signal outputs. In this proof-of-principle work, we attempted to address these problems by utilizing multi-functional peptide probes and the peptide-mediated nanoparticle assembly system. Here, the rationally designed peptide probes function as the dual-target responsive element specifically responsive to metal ions and enzymes as well as the mediator regulating the assembly of gold nanoparticles (AuNPs). Taking advantage of Zn2+ ions and chymotrypsin as the model inputs of metal ions and enzymes, respectively, we constructed the peptide logic system computed by the multi-functional peptide probes and outputted by the readable colour change of AuNPs. In this way, the representative binary basic logic gates (AND, OR, INHIBIT, NAND, IMPLICATION) have been achieved by delicately coding the peptide sequence, demonstrating the versatility of our logic system. Additionally, we demonstrated that the three-input combinational logic gate (INHIBIT-OR) could also be successfully integrated and applied as a multi-tasking biosensor for colorimetric detection of dual targets. This nanoparticle-based peptide logic system presents a valid strategy to illustrate peptide information processing and provides a practical platform for executing peptide computing or peptide-related multiplexing sensing, implying that the controllable nanomaterial assembly is a promising and potent methodology for the advancement of biomimetic bio-logic computation.In natural biological systems, proteins exploit various functional peptide motifs to exert target response and activity switch, providing a functional and logic basis for complex cellular activities. Building biomimetic peptide-based bio-logic systems is highly intriguing but remains relatively unexplored due to limited logic recognition elements and complex signal outputs. In this proof-of-principle work, we attempted to address these problems by utilizing multi-functional peptide probes and the peptide-mediated nanoparticle assembly system. Here, the rationally designed peptide probes function as the dual-target responsive element specifically responsive to metal ions and enzymes as well as the mediator regulating the assembly of gold nanoparticles (AuNPs). Taking advantage of Zn2+ ions and chymotrypsin as the model inputs of metal ions and enzymes, respectively, we constructed the peptide logic system computed by the multi-functional peptide probes and outputted by the readable colour change of AuNPs. In this way, the representative binary basic logic gates (AND, OR, INHIBIT, NAND, IMPLICATION) have been achieved by delicately coding the peptide sequence, demonstrating the versatility of our logic system. Additionally, we demonstrated that the three-input combinational logic gate (INHIBIT-OR) could also be successfully integrated and applied as a multi-tasking biosensor for colorimetric detection of dual targets. This nanoparticle-based peptide logic system presents a valid strategy to illustrate peptide information processing and provides a practical platform for executing peptide computing or peptide-related multiplexing sensing, implying that the controllable nanomaterial assembly is a promising and potent methodology for the advancement of biomimetic bio-logic computation. Electronic supplementary information (ESI) available: Additional figures (Tables S1-S3 and Fig. S1-S6). See DOI: 10.1039/c6nr01072e

RAFT Nano-constructs: surfing to biological applications.

PubMed

Boturyn, Didier; Defrancq, Eric; Dolphin, Gunnar T; Garcia, Julian; Labbe, Pierre; Renaudet, Olivier; Dumy, Pascal

2008-02-01

Biologically programmed molecular recognition provides the basis of all natural systems and supplies evolution-optimized functional materials from self-assembly of a limited number of molecular building blocks. Biomolecules such as peptides, nucleic acids and carbohydrates represent a diverse supply of structural building blocks for the chemist to design and fabricate new functional nanostructured architectures. In this context, we review here the chemistry we have developed to conjugate peptides with nucleic acids, carbohydrates, and organic molecules, as well as combinations thereof using a template-assembled approach. With this methodology, we have prepared new integrated functional systems exhibiting designed properties in the field of nanovectors, biosensors as well as controlled peptide self-assembly. Thus this molecular engineering approach allows for the rational design of systems with integrated tailor-made properties and paves the way to more elaborate applications by bottom-up design in the domain of nanobiosciences.

Recent Advances in Marine Algae Polysaccharides: Isolation, Structure, and Activities.

PubMed

Xu, Shu-Ying; Huang, Xuesong; Cheong, Kit-Leong

2017-12-13

Marine algae have attracted a great deal of interest as excellent sources of nutrients. Polysaccharides are the main components in marine algae, hence a great deal of attention has been directed at isolation and characterization of marine algae polysaccharides because of their numerous health benefits. In this review, extraction and purification approaches and chemico-physical properties of marine algae polysaccharides (MAPs) are summarized. The biological activities, which include immunomodulatory, antitumor, antiviral, antioxidant, and hypolipidemic, are also discussed. Additionally, structure-function relationships are analyzed and summarized. MAPs' biological activities are closely correlated with their monosaccharide composition, molecular weights, linkage types, and chain conformation. In order to promote further exploitation and utilization of polysaccharides from marine algae for functional food and pharmaceutical areas, high efficiency, and low-cost polysaccharide extraction and purification methods, quality control, structure-function activity relationships, and specific mechanisms of MAPs activation need to be extensively investigated.

Myosin motor function: the ins and outs of actin-based membrane protrusions

PubMed Central

Nambiar, Rajalakshmi; McConnell, Russell E.

2011-01-01

Cells build plasma membrane protrusions supported by parallel bundles of F-actin to enable a wide variety of biological functions, ranging from motility to host defense. Filopodia, microvilli and stereocilia are three such protrusions that have been the focus of intense biological and biophysical investigation in recent years. While it is evident that actin dynamics play a significant role in the formation of these organelles, members of the myosin superfamily have also been implicated as key players in the maintenance of protrusion architecture and function. Based on a simple analysis of the physical forces that control protrusion formation and morphology, as well as our review of available data, we propose that myosins play two general roles within these structures: (1) as cargo transporters to move critical regulatory components toward distal tips and (2) as mediators of membrane-cytoskeleton adhesion. PMID:20107861

Materials learning from life: concepts for active, adaptive and autonomous molecular systems.

PubMed

Merindol, Rémi; Walther, Andreas

2017-09-18

Bioinspired out-of-equilibrium systems will set the scene for the next generation of molecular materials with active, adaptive, autonomous, emergent and intelligent behavior. Indeed life provides the best demonstrations of complex and functional out-of-equilibrium systems: cells keep track of time, communicate, move, adapt, evolve and replicate continuously. Stirred by the understanding of biological principles, artificial out-of-equilibrium systems are emerging in many fields of soft matter science. Here we put in perspective the molecular mechanisms driving biological functions with the ones driving synthetic molecular systems. Focusing on principles that enable new levels of functionalities (temporal control, autonomous structures, motion and work generation, information processing) rather than on specific material classes, we outline key cross-disciplinary concepts that emerge in this challenging field. Ultimately, the goal is to inspire and support new generations of autonomous and adaptive molecular devices fueled by self-regulating chemistry.

A modular approach for multifunctional polymersomes with controlled adhesive properties.

PubMed

Petit, Julien; Thomi, Laura; Schultze, Jennifer; Makowski, Marcin; Negwer, Inka; Koynov, Kaloian; Herminghaus, Stephan; Wurm, Frederik R; Bäumchen, Oliver; Landfester, Katharina

2018-02-14

The bottom-up approach in synthetic biology involves the engineering of synthetic cells by designing biological and chemical building blocks, which can be combined in order to mimic cellular functions. The first step for mimicking a living cell is the design of an appropriate compartment featuring a multifunctional membrane. This is of particular interest since it allows for the selective attachment of different groups or molecules to the membrane. In this context, we report on a modular approach for polymeric vesicles, so-called polymersomes, with a multifunctional surface, namely hydroxyl, alkyne and acrylate groups. We demonstrate that the surface of the polymersome can be functionalized to facilitate imaging, via fluorescent dyes, or to improve the specific adhesion to surfaces by using a biotin functionalization. This generally applicable multifunctionality allows for the covalent integration of various molecules in the membrane of a synthetic cell.

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.

Chilocorus cacti (Coleoptera: Coccinellidae) as a Biological Control Agent of the Wild Cochineal (Hemiptera: Dactylopiidae) of Prickly Pear Cactus.

PubMed

Hernández-González, I A; Cruz-Rodríguez, J A

2018-04-05

The wild cochineal (Dactylopius opuntiae Cockerell) (Hemiptera: Dactylopiidae) is considered to be the most important pest in cactus pear plantations. In Mexico, there are seven natural enemies that provide natural biological control of D. opuntiae. However, their role and impact have not been evaluated. In this article, we report on aspects of the population biology of Chilocorus cacti L. (Coleoptera: Coccinellidae), which is considered one of the main natural enemies of D. opuntiae. We also conducted experiments to evaluate the consumption of C. cacti by this predator when fed nymphs and adult females of D. opuntiae. Changes in the survival function of D. opuntiae in the presence or absence C. cacti were also identified. Both larvae and adults of C. cacti prefer to consume D. opuntiae nymphs because the wax produced by adult females presents a significant obstacle. The survival analysis showed that the presence of C. cacti had significant negative effects on D. opuntiae survival. C. cacti significantly increased its abundance while reducing the density of adult female D. opuntiae, but this impact occurred only after they had consumed the more preferred nymphs. For this reason, natural enemies other than C. cacti may be required to achieve adequate levels of biological control.

Risk-adaptive radiotherapy

NASA Astrophysics Data System (ADS)

Kim, Yusung

Currently, there is great interest in integrating biological information into intensity-modulated radiotherapy (IMRT) treatment planning with the aim of boosting high-risk tumor subvolumes. Selective boosting of tumor subvolumes can be accomplished without violating normal tissue complication constraints using information from functional imaging. In this work we have developed a risk-adaptive optimization-framework that utilizes a nonlinear biological objective function. Employing risk-adaptive radiotherapy for prostate cancer, it is possible to increase the equivalent uniform dose (EUD) by up to 35.4 Gy in tumor subvolumes having the highest risk classification without increasing normal tissue complications. Subsequently, we have studied the impact of functional imaging accuracy, and found on the one hand that loss in sensitivity had a large impact on expected local tumor control, which was maximal when a low-risk classification for the remaining low risk PTV was chosen. While on the other hand loss in specificity appeared to have a minimal impact on normal tissue sparing. Therefore, it appears that in order to improve the therapeutic ratio a functional imaging technique with a high sensitivity, rather than specificity, is needed. Last but not least a comparison study between selective boosting IMRT strategies and uniform-boosting IMRT strategies yielding the same EUD to the overall PTV was carried out, and found that selective boosting IMRT considerably improves expected TCP compared to uniform-boosting IMRT, especially when lack of control of the high-risk tumor subvolumes is the cause of expected therapy failure. Furthermore, while selective boosting IMRT, using physical dose-volume objectives, did yield similar rectal and bladder sparing when compared its equivalent uniform-boosting IMRT plan, risk-adaptive radiotherapy, utilizing biological objective functions, did yield a 5.3% reduction in NTCP for the rectum. Hence, in risk-adaptive radiotherapy the therapeutic ratio can be increased over that which can be achieved with conventional selective boosting IMRT using physical dose-volume objectives. In conclusion, a novel risk-adaptive radiotherapy strategy is proposed and promises increased expected local control for locoregionally advanced tumors with equivalent or better normal tissue sparing.

Scanning number and brightness yields absolute protein concentrations in live cells: a crucial parameter controlling functional bio-molecular interaction networks.

PubMed

Papini, Christina; Royer, Catherine A

2018-02-01

Biological function results from properly timed bio-molecular interactions that transduce external or internal signals, resulting in any number of cellular fates, including triggering of cell-state transitions (division, differentiation, transformation, apoptosis), metabolic homeostasis and adjustment to changing physical or nutritional environments, amongst many more. These bio-molecular interactions can be modulated by chemical modifications of proteins, nucleic acids, lipids and other small molecules. They can result in bio-molecular transport from one cellular compartment to the other and often trigger specific enzyme activities involved in bio-molecular synthesis, modification or degradation. Clearly, a mechanistic understanding of any given high level biological function requires a quantitative characterization of the principal bio-molecular interactions involved and how these may change dynamically. Such information can be obtained using fluctation analysis, in particular scanning number and brightness, and used to build and test mechanistic models of the functional network to define which characteristics are the most important for its regulation.

Detection of driver metabolites in the human liver metabolic network using structural controllability analysis

PubMed Central

2014-01-01

Background Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. Results We applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism. Conclusion There are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism. PMID:24885538

Chemical biology based on target-selective degradation of proteins and carbohydrates using light-activatable organic molecules.

PubMed

Toshima, Kazunobu

2013-05-01

Proteins and carbohydrates play crucial roles in a wide range of biological processes, including serious diseases. The development of novel and innovative methods for selective control of specific proteins and carbohydrates functions has attracted much attention in the field of chemical biology. In this account article, the development of novel chemical tools, which can degrade target proteins and carbohydrates by irradiation with a specific wavelength of light under mild conditions without any additives, is introduced. This novel class of photochemical agents promise bright prospects for finding not only molecular-targeted bioprobes for understanding of the structure-activity relationships of proteins and carbohydrates but also novel therapeutic drugs targeting proteins and carbohydrates.

Nanogel Carrier Design for Targeted Drug Delivery

PubMed Central

Eckmann, D. M.; Composto, R. J.; Tsourkas, A.; Muzykantov, V. R.

2014-01-01

Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli. These unique features and low toxicity make the nanogels a favorable option for vascular drug targeting. In this review, we address key chemical and biological aspects of nanogel drug carrier design. In particular, we highlight published studies of nanogel design, descriptions of nanogel functional characteristics and their behavior in biological models. These studies form a compendium of information that supports the scientific and clinical rationale for development of this carrier for targeted therapeutic interventions. PMID:25485112

Molecular phenology in plants: in natura systems biology for the comprehensive understanding of seasonal responses under natural environments.

PubMed

Kudoh, Hiroshi

2016-04-01

Phenology refers to the study of seasonal schedules of organisms. Molecular phenology is defined here as the study of the seasonal patterns of organisms captured by molecular biology techniques. The history of molecular phenology is reviewed briefly in relation to advances in the quantification technology of gene expression. High-resolution molecular phenology (HMP) data have enabled us to study phenology with an approach of in natura systems biology. I review recent analyses of FLOWERING LOCUS C (FLC), a temperature-responsive repressor of flowering, along the six steps in the typical flow of in natura systems biology. The extensive studies of the regulation of FLC have made this example a successful case in which a comprehensive understanding of gene functions has been progressing. The FLC-mediated long-term memory of past temperatures creates time lags with other seasonal signals, such as photoperiod and short-term temperature. Major signals that control flowering time have a phase lag between them under natural conditions, and hypothetical phase lag calendars are proposed as mechanisms of season detection in plants. Transcriptomic HMP brings a novel strategy to the study of molecular phenology, because it provides a comprehensive representation of plant functions. I discuss future perspectives of molecular phenology from the standpoints of molecular biology, evolutionary biology and ecology. © 2015 The Author. New Phytologist © 2015 New Phytologist Trust.

Structure-function relationship of skeletal muscle provides inspiration for design of new artificial muscle

NASA Astrophysics Data System (ADS)

Gao, Yingxin; Zhang, Chi

2015-03-01

A variety of actuator technologies have been developed to mimic biological skeletal muscle that generates force in a controlled manner. Force generation process of skeletal muscle involves complicated biophysical and biochemical mechanisms; therefore, it is impossible to replace biological muscle. In biological skeletal muscle tissue, the force generation of a muscle depends not only on the force generation capacity of the muscle fiber, but also on many other important factors, including muscle fiber type, motor unit recruitment, architecture, structure and morphology of skeletal muscle, all of which have significant impact on the force generation of the whole muscle or force transmission from muscle fibers to the tendon. Such factors have often been overlooked, but can be incorporated in artificial muscle design, especially with the discovery of new smart materials and the development of innovative fabrication and manufacturing technologies. A better understanding of the physiology and structure-function relationship of skeletal muscle will therefore benefit the artificial muscle design. In this paper, factors that affect muscle force generation are reviewed. Mathematical models used to model the structure-function relationship of skeletal muscle are reviewed and discussed. We hope the review will provide inspiration for the design of a new generation of artificial muscle by incorporating the structure-function relationship of skeletal muscle into the design of artificial muscle.

Redox Pioneer: Professor Vadim N. Gladyshev.

PubMed

Hatfield, Dolph L

2016-07-01

Professor Vadim N. Gladyshev is recognized here as a Redox Pioneer, because he has published an article on antioxidant/redox biology that has been cited more than 1000 times and 29 articles that have been cited more than 100 times. Gladyshev is world renowned for his characterization of the human selenoproteome encoded by 25 genes, identification of the majority of known selenoprotein genes in the three domains of life, and discoveries related to thiol oxidoreductases and mechanisms of redox control. Gladyshev's first faculty position was in the Department of Biochemistry, the University of Nebraska. There, he was a Charles Bessey Professor and Director of the Redox Biology Center. He then moved to the Department of Medicine at Brigham and Women's Hospital, Harvard Medical School, where he is Professor of Medicine and Director of the Center for Redox Medicine. His discoveries in redox biology relate to selenoenzymes, such as methionine sulfoxide reductases and thioredoxin reductases, and various thiol oxidoreductases. He is responsible for the genome-wide identification of catalytic redox-active cysteines and for advancing our understanding of the general use of cysteines by proteins. In addition, Gladyshev has characterized hydrogen peroxide metabolism and signaling and regulation of protein function by methionine-R-sulfoxidation. He has also made important contributions in the areas of aging and lifespan control and pioneered applications of comparative genomics in redox biology, selenium biology, and aging. Gladyshev's discoveries have had a profound impact on redox biology and the role of redox control in health and disease. He is a true Redox Pioneer. Antioxid. Redox Signal. 25, 1-9.

Redox Pioneer: Professor Vadim N. Gladyshev

PubMed Central

2016-01-01

Abstract Professor Vadim N. Gladyshev is recognized here as a Redox Pioneer, because he has published an article on antioxidant/redox biology that has been cited more than 1000 times and 29 articles that have been cited more than 100 times. Gladyshev is world renowned for his characterization of the human selenoproteome encoded by 25 genes, identification of the majority of known selenoprotein genes in the three domains of life, and discoveries related to thiol oxidoreductases and mechanisms of redox control. Gladyshev's first faculty position was in the Department of Biochemistry, the University of Nebraska. There, he was a Charles Bessey Professor and Director of the Redox Biology Center. He then moved to the Department of Medicine at Brigham and Women's Hospital, Harvard Medical School, where he is Professor of Medicine and Director of the Center for Redox Medicine. His discoveries in redox biology relate to selenoenzymes, such as methionine sulfoxide reductases and thioredoxin reductases, and various thiol oxidoreductases. He is responsible for the genome-wide identification of catalytic redox-active cysteines and for advancing our understanding of the general use of cysteines by proteins. In addition, Gladyshev has characterized hydrogen peroxide metabolism and signaling and regulation of protein function by methionine-R-sulfoxidation. He has also made important contributions in the areas of aging and lifespan control and pioneered applications of comparative genomics in redox biology, selenium biology, and aging. Gladyshev's discoveries have had a profound impact on redox biology and the role of redox control in health and disease. He is a true Redox Pioneer. Antioxid. Redox Signal. 25, 1–9. PMID:26984707

A dedicated database system for handling multi-level data in systems biology.

PubMed

Pornputtapong, Natapol; Wanichthanarak, Kwanjeera; Nilsson, Avlant; Nookaew, Intawat; Nielsen, Jens

2014-01-01

Advances in high-throughput technologies have enabled extensive generation of multi-level omics data. These data are crucial for systems biology research, though they are complex, heterogeneous, highly dynamic, incomplete and distributed among public databases. This leads to difficulties in data accessibility and often results in errors when data are merged and integrated from varied resources. Therefore, integration and management of systems biological data remain very challenging. To overcome this, we designed and developed a dedicated database system that can serve and solve the vital issues in data management and hereby facilitate data integration, modeling and analysis in systems biology within a sole database. In addition, a yeast data repository was implemented as an integrated database environment which is operated by the database system. Two applications were implemented to demonstrate extensibility and utilization of the system. Both illustrate how the user can access the database via the web query function and implemented scripts. These scripts are specific for two sample cases: 1) Detecting the pheromone pathway in protein interaction networks; and 2) Finding metabolic reactions regulated by Snf1 kinase. In this study we present the design of database system which offers an extensible environment to efficiently capture the majority of biological entities and relations encountered in systems biology. Critical functions and control processes were designed and implemented to ensure consistent, efficient, secure and reliable transactions. The two sample cases on the yeast integrated data clearly demonstrate the value of a sole database environment for systems biology research.

Comparative study of time-dependent effects of 4 and 8 Hz mechanical vibration at infrasound frequency on E. coli K-12 cells proliferation.

PubMed

Martirosyan, Varsik; Ayrapetyan, Sinerik

2015-01-01

The aim of the present work is to study the time-dependent effects of mechanical vibration (MV) at infrasound (IS) frequency at 4 and 8 Hz on E. coli K-12 growth by investigating the cell proliferation, using radioactive [(3)H]-thymidine assay. In our previous work it was suggested that the aqua medium can serve as a target through which the biological effect of MV on microbes could be realized. At the same time it was shown that microbes have mechanosensors on the surface of the cells and can sense small changes of the external environment. The obtained results were shown that the time-dependent effects of MV at 4 and 8 Hz frequency could either stimulate or inhibit the growth of microbes depending from exposure time. It more particularly, the invention relates to a method for controlling biological functions through the application of mechanical vibration, thus making it possible to artificially control the functions of bacterial cells, which will allow us to develop method that can be used in agriculture, industry, medicine, biotechnology to control microbial growth.

Coparenting Conflict and Academic Readiness in Children of Teen Mothers: Effortful Control as a Mediator.

PubMed

Jahromi, Laudan B; Zeiders, Katharine H; Updegraff, Kimberly A; Umaña-Taylor, Adriana J; Bayless, Sara Douglass

2017-04-24

Children's exposure to coparenting conflict has important implications for their developmental functioning, yet limited work has focused on such processes in families with diverse structures or ethnically and culturally diverse backgrounds. This longitudinal study examined the processes by which Mexican-origin adolescent mothers' coparenting conflict with their 3-year-old children's grandmothers and biological fathers (N = 133 families) were linked to children's academic and social skills at 5 years of age, and whether children's effortful control at 4 years of age mediated the link between coparenting conflict and indices of children's academic readiness. Findings revealed that adolescent mothers' coparenting conflict with their child's biological father was linked to indices of children's academic and social school readiness through children's effortful control among girls, but not boys, whereas conflict with grandmothers was directly linked to boys' and girls' social functioning 2 years later. Findings offer information about different mechanisms by which multiple coparenting units in families of adolescent mothers are related to their children's outcomes, and this work has important implications for practitioners working with families of adolescent mothers. © 2017 Family Process Institute.

Tissue vascularization through 3D printing: Will technology bring us flow?

PubMed

Paulsen, S J; Miller, J S

2015-05-01

Though in vivo models provide the most physiologically relevant environment for studying tissue function, in vitro studies provide researchers with explicit control over experimental conditions and the potential to develop high throughput testing methods. In recent years, advancements in developmental biology research and imaging techniques have significantly improved our understanding of the processes involved in vascular development. However, the task of recreating the complex, multi-scale vasculature seen in in vivo systems remains elusive. 3D bioprinting offers a potential method to generate controlled vascular networks with hierarchical structure approaching that of in vivo networks. Bioprinting is an interdisciplinary field that relies on advances in 3D printing technology along with advances in imaging and computational modeling, which allow researchers to monitor cellular function and to better understand cellular environment within the printed tissue. As bioprinting technologies improve with regards to resolution, printing speed, available materials, and automation, 3D printing could be used to generate highly controlled vascularized tissues in a high throughput manner for use in regenerative medicine and the development of in vitro tissue models for research in developmental biology and vascular diseases. © 2015 Wiley Periodicals, Inc.

Cognitive control dysfunction and abnormal frontal cortex activation in stimulant drug users and their biological siblings.

PubMed

Smith, D G; Jones, P S; Bullmore, E T; Robbins, T W; Ersche, K D

2013-05-14

Cognitive and neural abnormalities are known to accompany chronic drug abuse, with impairments in cognition and changes in cortical structure seen in stimulant-dependent individuals. However, premorbid differences have also been observed in the brains and behavior of individuals at risk for substance abuse, before they develop dependence. Endophenotype research has emerged as a useful method for assessing preclinical traits that may be risk factors for pathology by studying patient populations and their undiagnosed first-degree relatives. This study used the color-word Stroop task to assess executive functioning in stimulant-dependent individuals, their unaffected biological siblings and unrelated healthy control volunteers using a functional magnetic resonance imaging paradigm. Both the stimulant-dependent and sibling participants demonstrated impairments in cognitive control and processing speed on the task, registering significantly longer response latencies. However, the two groups generated very different neural responses, with the sibling participants exhibiting a significant decrease in activation in the inferior frontal gyrus compared with both stimulant-dependent individuals and control participants. Both target groups also demonstrated a decrease in hemispheric laterality throughout the task, exhibiting a disproportionate increase in right hemispheric activation, which was associated with their behavioral inefficiencies. These findings not only suggest a possible risk factor for stimulant abuse of poor inhibitory control and cortical inefficiency but they also demonstrate possible adaptations in the brains of stimulant users.

PyMOL mControl: Manipulating molecular visualization with mobile devices.

PubMed

Lam, Wendy W T; Siu, Shirley W I

2017-01-02

Viewing and manipulating three-dimensional (3D) structures in molecular graphics software are essential tasks for researchers and students to understand the functions of molecules. Currently, the way to manipulate a 3D molecular object is mainly based on mouse-and-keyboard control that is usually difficult and tedious to learn. While gesture-based and touch-based interactions are increasingly popular in interactive software systems, their suitability in handling molecular graphics has not yet been sufficiently explored. Here, we designed the gesture-based and touch-based interaction methods to manipulate virtual objects in PyMOL utilizing the motion and touch sensors in a mobile device. Three fundamental viewing controls-zooming, translation and rotation-and frequently used functions were implemented. Results from a pilot user study reveal that task performances on viewing controls using a mobile device are slightly reduced as compared to mouse-and-keyboard method. However, it is considered to be more suitable for oral presentations and equally suitable for education scenarios such as school classes. Overall, PyMOL mControl provides an alternative way to manipulate objects in molecular graphic software with new user experiences. The software is freely available at http://cbbio.cis.umac.mo/mcontrol.html. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):76-83, 2017. © 2016 The International Union of Biochemistry and Molecular Biology.

Synchrony of corticostriatal-midbrain activation enables normal inhibitory control and conflict processing in recovering alcoholic men.

PubMed

Schulte, Tilman; Müller-Oehring, Eva M; Sullivan, Edith V; Pfefferbaum, Adolf

2012-02-01

Alcohol dependence is associated with inhibitory control deficits, possibly related to abnormalities in frontoparietal cortical and midbrain function and connectivity. We examined functional connectivity and microstructural fiber integrity between frontoparietal and midbrain structures using a Stroop Match-to-Sample task with functional magnetic resonance imaging and diffusion tensor imaging in 18 alcoholic and 17 control subjects. Manipulation of color cues and response repetition sequences modulated cognitive demands during Stroop conflict. Despite similar lateral frontoparietal activity and functional connectivity in alcoholic and control subjects when processing conflict, control subjects deactivated the posterior cingulate cortex (PCC), whereas alcoholic subjects did not. Posterior cingulum fiber integrity predicted the degree of PCC deactivation in control but not alcoholic subjects. Also, PCC activity was modulated by executive control demands: activated during response switching and deactivated during response repetition. Alcoholics showed the opposite pattern: activation during repetition and deactivation during switching. Here, in alcoholic subjects, greater deviations from the normal PCC activity correlated with higher amounts of lifetime alcohol consumption. A functional dissociation of brain network connectivity between the groups further showed that control subjects exhibited greater corticocortical connectivity among middle cingulate, posterior cingulate, and medial prefrontal cortices than alcoholic subjects. In contrast, alcoholic subjects exhibited greater midbrain-orbitofrontal cortical network connectivity than control subjects. Degree of microstructural fiber integrity predicted robustness of functional connectivity. Thus, even subtle compromise of microstructural connectivity in alcoholism can influence modulation of functional connectivity and underlie alcohol-related cognitive impairment. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Analysis of a predator-prey model with Holling II functional response concerning impulsive control strategy

NASA Astrophysics Data System (ADS)

Liu, Bing; Teng, Zhidong; Chen, Lansun

2006-08-01

According to biological and chemical control strategy for pest control, we investigate the dynamic behavior of a Holling II functional response predator-prey system concerning impulsive control strategy-periodic releasing natural enemies and spraying pesticide at different fixed times. By using Floquet theorem and small amplitude perturbation method, we prove that there exists a stable pest-eradication periodic solution when the impulsive period is less than some critical value. Further, the condition for the permanence of the system is also given. Numerical results show that the system we consider can take on various kinds of periodic fluctuations and several types of attractor coexistence and is dominated by periodic, quasiperiodic and chaotic solutions, which implies that the presence of pulses makes the dynamic behavior more complex. Finally, we conclude that our impulsive control strategy is more effective than the classical one if we take chemical control efficiently.

Relationship between alertness, performance, and body temperature in humans.

PubMed

Wright, Kenneth P; Hull, Joseph T; Czeisler, Charles A

2002-12-01

Body temperature has been reported to influence human performance. Performance is reported to be better when body temperature is high/near its circadian peak and worse when body temperature is low/near its circadian minimum. We assessed whether this relationship between performance and body temperature reflects the regulation of both the internal biological timekeeping system and/or the influence of body temperature on performance independent of circadian phase. Fourteen subjects participated in a forced desynchrony protocol allowing assessment of the relationship between body temperature and performance while controlling for circadian phase and hours awake. Most neurobehavioral measures varied as a function of internal biological time and duration of wakefulness. A number of performance measures were better when body temperature was elevated, including working memory, subjective alertness, visual attention, and the slowest 10% of reaction times. These findings demonstrate that an increased body temperature, associated with and independent of internal biological time, is correlated with improved performance and alertness. These results support the hypothesis that body temperature modulates neurobehavioral function in humans.

Modifying the 5'-Cap for Click Reactions of Eukaryotic mRNA and To Tune Translation Efficiency in Living Cells.

PubMed

Holstein, Josephin M; Anhäuser, Lea; Rentmeister, Andrea

2016-08-26

The 5'-cap is a hallmark of eukaryotic mRNAs and plays fundamental roles in RNA metabolism, ranging from quality control to export and translation. Modifying the 5'-cap may thus enable modulation of the underlying processes and investigation or tuning of several biological functions. A straightforward approach is presented for the efficient production of a range of N7-modified caps based on the highly promiscuous methyltransferase Ecm1. We show that these, as well as N(2) -modified 5'-caps, can be used to tune translation of the respective mRNAs both in vitro and in cells. Appropriate modifications allow subsequent bioorthogonal chemistry, as demonstrated by intracellular live-cell labeling of a target mRNA. The efficient and versatile N7 manipulation of the mRNA cap makes mRNAs amenable to both modulation of their biological function and intracellular labeling, and represents a valuable addition to the chemical biology toolbox. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Relationship between alertness, performance, and body temperature in humans

NASA Technical Reports Server (NTRS)

Wright, Kenneth P Jr; Hull, Joseph T.; Czeisler, Charles A.

2002-01-01

Body temperature has been reported to influence human performance. Performance is reported to be better when body temperature is high/near its circadian peak and worse when body temperature is low/near its circadian minimum. We assessed whether this relationship between performance and body temperature reflects the regulation of both the internal biological timekeeping system and/or the influence of body temperature on performance independent of circadian phase. Fourteen subjects participated in a forced desynchrony protocol allowing assessment of the relationship between body temperature and performance while controlling for circadian phase and hours awake. Most neurobehavioral measures varied as a function of internal biological time and duration of wakefulness. A number of performance measures were better when body temperature was elevated, including working memory, subjective alertness, visual attention, and the slowest 10% of reaction times. These findings demonstrate that an increased body temperature, associated with and independent of internal biological time, is correlated with improved performance and alertness. These results support the hypothesis that body temperature modulates neurobehavioral function in humans.

Treatment of ankylosing spondylitis with biologics and targeted physical therapy: positive effect on chest pain, diminished chest mobility, and respiratory function.

PubMed

Gyurcsik, Z; Bodnár, N; Szekanecz, Z; Szántó, S

2013-12-01

Biologics are highly effective in ankylosing spondylitis (AS). In this self-controlled study, we assessed the additive value of complex physiotherapy in decreasing chest pain and tenderness and improving respiratory function in AS patients treated with tumor necrosis factor α (TNF-α) inhibitors. The trial consisted of 2 parts. In study I, clinical data of AS patients with (n=55) or without biological therapy (n=20) were retrospectively analyzed and compared. Anthropometrical data, duration since diagnosis and patient assessment of disease activity, pain intensity, tender points, sacroiliac joint involvement determined by X-ray, functional condition, and physical activity level were recorded. Subjective, functional, and physical tests were performed. In study II, 10 voluntary patients (6 men and 4 women, age 52.4 ± 13.6 years) with definite AS and receiving anti-TNF therapy were recruited. It was a prospective, non-randomized physiotherapeutic trial. BASFI (Bath Ankylosing Spondylitis Functional Index), BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), modified Schober Index, occiput-to-wall distance, and fingertip-to-floor distance were evaluated. Forced vital capacity, forced 1-s expiratory volume, peak expiratory flow, and maximum voluntary ventilation were recorded. Furthermore, typical tender points were recorded. A targeted physiotherapy program was conducted twice a week for 12 weeks and all above parameters were recorded at baseline and after 12 weeks. Differences in patient assessment of disease activity (p=0.019) and pain intensity (p=0.017) were found in study I. Pain and tenderness of the thoracic spine were observed in both groups. Back pain without biologic therapy was slightly higher than other group. In study II, we found that patient assessment of disease activity and pain intensity significantly improved after the physical therapy program (p=0.002 and p<0.001). BASFI and BASDAI increased after treatment (p=0.004 and p<0.001). The finger-to-floor distance, chest expansion, and modified Schober index increased (p=0.008, p<0.001, and p=0.031, respectively). The respiratory functional parameters showed a tendency towards improvement. AS patients already receiving biological therapy may benefit from additional targeted physiotherapy. Physical therapy may be of important additive value in AS patients being treated with biological. The exercise program presented here showed an improvement in functional parameters as well as spine and chest mobility, thereby enhancing the favorable effects of biological therapy.

Religious groups as adaptive units.

PubMed

Wilson, D S

2001-01-01

This essay provides a sketch of religion as a set of biologically and culturally evolved adaptations that enable human groups to function as adaptive units. Recent developments in evolutionary biology make such a group-level interpretation of religion more plausible than in the past. A brief survey of relevant concepts is followed by a relatively detailed interpretation of Calvinism as a religious system in which explicit behavioral prescriptions, beliefs about God and his relationship with people, and numerous social control mechanisms combined to change the city of Geneva from a collection of warring factions to a unified population.

Nanostructures Enabled by On-Wire Lithography (OWL)

PubMed Central

Braunschweig, Adam B.; Schmucker, Abrin L.; Wei, Wei David; Mirkin, Chad A.

2010-01-01

Nanostructures fabricated by a novel technique, termed On-Wire-Lithography (OWL), can be combined with organic and biological molecules to create systems with emergent and highly functional properties. OWL is a template-based, electrochemical process for forming gapped cylindrical structures on a solid support, with feature sizes (both gap and segment length) that can be controlled on the sub-100 nm length scale. Structures prepared by this method have provided valuable insight into the plasmonic properties of noble metal nanomaterials and have formed the basis for novel molecular electronic, encoding, and biological detection devices. PMID:20396668

Functionalized Nanodiamonds for Biological and Medical Applications.

PubMed

Lai, Lin; Barnard, Amanda S

2015-02-01

Nanodiamond is a promising material for biological and medical applications, owning to its relatively inexpensive and large-scale synthesis, unique structure, and superior optical properties. However, most biomedical applications, such as drug delivery and bio-imaging, are dependent upon the precise control of the surfaces, and can be significantly affected by the type, distribution and stability of chemical funtionalisations of the nanodiamond surface. In this paper, recent studies on nanodiamonds and their biomedical applications by conjugating with different chemicals are reviewed, while highlighting the critical importance of surface chemical states for various applications.

The Role of Suppressors of Cytokine Signalling in Human Neoplasms

PubMed Central

Sharma, Anup K.; Mokbel, Kefah

2014-01-01

Suppressors of cytokine signalling 1–7 (SOCS1–7) and cytokine-inducible SH2-containing protein (CIS) are a group of intracellular proteins that are well known as JAK-STAT and several other signalling pathways negative feedback regulators. More recently several members have been identified as tumour suppressors and dysregulation of their biological roles in controlling cytokine and growth factor signalling may contribute to the development of many solid organ and haematological malignancies. This review explores their biological functions and their possible tumour suppressing role in human neoplasms. PMID:24757565

Nanomaterials in the forest products industry

Treesearch

Robert J. Moon

2008-01-01

Nanotechnology is the study and engineering of matter at the dimensions of 1-100 nm where physical, chemical, or biological properties are fundamentally different from those of the bulk material. The nanotechnology paradigm is to modify bulk properties and functionality by controlled manipulations at the nanoscale. Nanotechnology research has dramatically grown within...

The role of proteolysis in the biological activity of Bt insecticidal crystal proteins

USDA-ARS?s Scientific Manuscript database

The crystal toxins (Cry) produced by the bacterium Bacillus thuringiensis have been successfully used in both spray formulations and transgenic crops to control some of the most problematic insect pests. The delta-endotoxins of B. thuringiensis are functionally-active in the insect gut and interact ...

Silvicultural and integrated pest management strategies for restoring eastern hemlock to degraded southern Appalachian mountain ecosystems.

Treesearch

W.A. Whittier; A.E. Mayfield III; R.M. Jetton

2017-01-01

The ecologically foundational species eastern hemlock, Tsuga canadensis, is being functionally eliminated from southern Appalachian forests by the hemlock woolly adelgid (HWA, Adelges tsugae). The management of HWA has focused on chemical and biological control, conservation of hemlock genetic resources, and host resistance...

76 FR 11075 - Schedules of Controlled Substances: Temporary Placement of Five Synthetic Cannabinoids Into...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-01

... of Abuse A ``cannabinoid'' is a class of chemical compounds in the marijuana plant that are... constituent of marijuana. ``Synthetic cannabinoids'' are a large family of chemically unrelated structures functionally (biologically) similar to THC, the active principle of marijuana. Two of the five synthetic...

Psychological Stress and Mitochondria: A Systematic Review.

PubMed

Picard, Martin; McEwen, Bruce S

Mitochondria are multifunctional life-sustaining organelles that represent a potential intersection point between psychosocial experiences and biological stress responses. This article provides a systematic review of the effects of psychological stress on mitochondrial structure and function. A systematic review of the literature investigating the effects of psychological stress on mitochondrial function was conducted. The review focused on experimentally controlled studies allowing us to draw causal inference about the effect of induced psychological stress on mitochondria. A total of 23 studies met the inclusion criteria. All studies involved male laboratory animals, and most demonstrated that acute and chronic stressors influenced specific facets of mitochondrial function, particularly within the brain. Nineteen studies showed significant adverse effects of psychological stress on mitochondria and four found increases in function or size after stress. In humans, only six observational studies were available, none with experimental designs, and most only measured biological markers that do not directly reflect mitochondrial function, such as mitochondrial DNA copy number. Overall, evidence supports the notion that acute and chronic stressors influence various aspects of mitochondrial biology, and that chronic stress exposure can lead to molecular and functional recalibrations among mitochondria. Limitations of current animal and human studies are discussed. Maladaptive mitochondrial changes that characterize this subcellular state of stress are termed mitochondrial allostatic load. Prospective studies with sensitive measures of specific mitochondrial outcomes will be needed to establish the link between psychosocial stressors, emotional states, the resulting neuroendocrine and immune processes, and mitochondrial energetics relevant to mind-body research in humans.

A roadmap to success in photopharmacology.

PubMed

Broichhagen, Johannes; Frank, James Allen; Trauner, Dirk

2015-07-21

Light is a fascinating phenomenon that ties together physics, chemistry, and biology. It is unmatched in its ability to confer information with temporal and spatial precision and has been used to map objects on the scale of tens of nanometers (10(-8) m) to light years (10(16) m). This information, gathered through super-resolution microscopes or space-based telescopes, is ultimately funneled through the human visual system, which is a miracle in itself. It allows us to see the Andromeda galaxy at night, an object that is 2.5 million light years away and very dim, and ski the next day in bright sunlight at an intensity that is 12 orders of magnitude higher. Human vision is only one of many photoreceptive systems that have evolved on earth and are found in all kingdoms of life. These systems rely on molecular photoswitches, such as retinal or tetrapyrrols, which undergo transient bond isomerizations or bond formations upon irradiation. The set of chromophores that have been employed in Nature for this purpose is surprisingly small. Nevertheless, they control a wide variety of biological functions, which have recently been significantly increased through the rapid development of optogenetics. Optogenetics originated as an effort to control neural function with genetically encoded photoreceptors that use abundant chromophores, in particular retinal. It now covers a variety of cellular functions other than excitability and has revolutionized the control of biological pathways in neuroscience and beyond. Chemistry has provided a large repertoire of synthetic photoswitches with highly tunable properties. Like their natural counterparts, these chromophores can be attached to proteins to effectively put them under optical control. This approach has enabled a new type of synthetic photobiology that has gone under various names to distinguish it from optogenetics. We now call it photopharmacology. Here we trace our involvement in this field, starting with the first light-sensitive potassium channel (SPARK) and concluding with our most recent work on photoswitchable fatty acids. Instead of simply providing a historical account of our efforts, we discuss the design criteria that guided our choice of molecules and receptors. As such, we hope to provide a roadmap to success in photopharmacology and make a case as to why synthetic photoswitches, properly designed and made available through well-planned and efficient syntheses, should have a bright future in biology and medicine.

Functional Proteomic Analysis of Human NucleolusD⃞

PubMed Central

Scherl, Alexander; Couté, Yohann; Déon, Catherine; Callé, Aleth; Kindbeiter, Karine; Sanchez, Jean-Charles; Greco, Anna; Hochstrasser, Denis; Diaz, Jean-Jacques

2002-01-01

The notion of a “plurifunctional” nucleolus is now well established. However, molecular mechanisms underlying the biological processes occurring within this nuclear domain remain only partially understood. As a first step in elucidating these mechanisms we have carried out a proteomic analysis to draw up a list of proteins present within nucleoli of HeLa cells. This analysis allowed the identification of 213 different nucleolar proteins. This catalog complements that of the 271 proteins obtained recently by others, giving a total of ∼350 different nucleolar proteins. Functional classification of these proteins allowed outlining several biological processes taking place within nucleoli. Bioinformatic analyses permitted the assignment of hypothetical functions for 43 proteins for which no functional information is available. Notably, a role in ribosome biogenesis was proposed for 31 proteins. More generally, this functional classification reinforces the plurifunctional nature of nucleoli and provides convincing evidence that nucleoli may play a central role in the control of gene expression. Finally, this analysis supports the recent demonstration of a coupling of transcription and translation in higher eukaryotes. PMID:12429849

The effects of small field dosimetry on the biological models used in evaluating IMRT dose distributions

NASA Astrophysics Data System (ADS)

Cardarelli, Gene A.

The primary goal in radiation oncology is to deliver lethal radiation doses to tumors, while minimizing dose to normal tissue. IMRT has the capability to increase the dose to the targets and decrease the dose to normal tissue, increasing local control, decrease toxicity and allow for effective dose escalation. This advanced technology does present complex dose distributions that are not easily verified. Furthermore, the dose inhomogeneity caused by non-uniform dose distributions seen in IMRT treatments has caused the development of biological models attempting to characterize the dose-volume effect in the response of organized tissues to radiation. Dosimetry of small fields can be quite challenging when measuring dose distributions for high-energy X-ray beams used in IMRT. The proper modeling of these small field distributions is essential in reproducing accurate dose for IMRT. This evaluation was conducted to quantify the effects of small field dosimetry on IMRT plan dose distributions and the effects on four biological model parameters. The four biological models evaluated were: (1) the generalized Equivalent Uniform Dose (gEUD), (2) the Tumor Control Probability (TCP), (3) the Normal Tissue Complication Probability (NTCP) and (4) the Probability of uncomplicated Tumor Control (P+). These models are used to estimate local control, survival, complications and uncomplicated tumor control. This investigation compares three distinct small field dose algorithms. Dose algorithms were created using film, small ion chamber, and a combination of ion chamber measurements and small field fitting parameters. Due to the nature of uncertainties in small field dosimetry and the dependence of biological models on dose volume information, this examination quantifies the effects of small field dosimetry techniques on radiobiological models and recommends pathways to reduce the errors in using these models to evaluate IMRT dose distributions. This study demonstrates the importance of valid physical dose modeling prior to the use of biological modeling. The success of using biological function data, such as hypoxia, in clinical IMRT planning will greatly benefit from the results of this study.

Decreased Functional Diversity and Biological Pest Control in Conventional Compared to Organic Crop Fields

PubMed Central

Krauss, Jochen; Gallenberger, Iris; Steffan-Dewenter, Ingolf

2011-01-01

Organic farming is one of the most successful agri-environmental schemes, as humans benefit from high quality food, farmers from higher prices for their products and it often successfully protects biodiversity. However there is little knowledge if organic farming also increases ecosystem services like pest control. We assessed 30 triticale fields (15 organic vs. 15 conventional) and recorded vascular plants, pollinators, aphids and their predators. Further, five conventional fields which were treated with insecticides were compared with 10 non-treated conventional fields. Organic fields had five times higher plant species richness and about twenty times higher pollinator species richness compared to conventional fields. Abundance of pollinators was even more than one-hundred times higher on organic fields. In contrast, the abundance of cereal aphids was five times lower in organic fields, while predator abundances were three times higher and predator-prey ratios twenty times higher in organic fields, indicating a significantly higher potential for biological pest control in organic fields. Insecticide treatment in conventional fields had only a short-term effect on aphid densities while later in the season aphid abundances were even higher and predator abundances lower in treated compared to untreated conventional fields. Our data indicate that insecticide treatment kept aphid predators at low abundances throughout the season, thereby significantly reducing top-down control of aphid populations. Plant and pollinator species richness as well as predator abundances and predator-prey ratios were higher at field edges compared to field centres, highlighting the importance of field edges for ecosystem services. In conclusion organic farming increases biodiversity, including important functional groups like plants, pollinators and predators which enhance natural pest control. Preventative insecticide application in conventional fields has only short-term effects on aphid densities but long-term negative effects on biological pest control. Therefore conventional farmers should restrict insecticide applications to situations where thresholds for pest densities are reached. PMID:21611171

Decreased functional diversity and biological pest control in conventional compared to organic crop fields.

PubMed

Krauss, Jochen; Gallenberger, Iris; Steffan-Dewenter, Ingolf

2011-01-01

Organic farming is one of the most successful agri-environmental schemes, as humans benefit from high quality food, farmers from higher prices for their products and it often successfully protects biodiversity. However there is little knowledge if organic farming also increases ecosystem services like pest control. We assessed 30 triticale fields (15 organic vs. 15 conventional) and recorded vascular plants, pollinators, aphids and their predators. Further, five conventional fields which were treated with insecticides were compared with 10 non-treated conventional fields. Organic fields had five times higher plant species richness and about twenty times higher pollinator species richness compared to conventional fields. Abundance of pollinators was even more than one-hundred times higher on organic fields. In contrast, the abundance of cereal aphids was five times lower in organic fields, while predator abundances were three times higher and predator-prey ratios twenty times higher in organic fields, indicating a significantly higher potential for biological pest control in organic fields. Insecticide treatment in conventional fields had only a short-term effect on aphid densities while later in the season aphid abundances were even higher and predator abundances lower in treated compared to untreated conventional fields. Our data indicate that insecticide treatment kept aphid predators at low abundances throughout the season, thereby significantly reducing top-down control of aphid populations. Plant and pollinator species richness as well as predator abundances and predator-prey ratios were higher at field edges compared to field centres, highlighting the importance of field edges for ecosystem services. In conclusion organic farming increases biodiversity, including important functional groups like plants, pollinators and predators which enhance natural pest control. Preventative insecticide application in conventional fields has only short-term effects on aphid densities but long-term negative effects on biological pest control. Therefore conventional farmers should restrict insecticide applications to situations where thresholds for pest densities are reached.

Evolving Concepts and Translational Relevance of Enteroendocrine Cell Biology.

PubMed

Drucker, Daniel J

2016-03-01

Classical enteroenteroendocrine cell (EEC) biology evolved historically from identification of scattered hormone-producing endocrine cells within the epithelial mucosa of the stomach, small and large intestine. Purification of functional EEC hormones from intestinal extracts, coupled with molecular cloning of cDNAs and genes expressed within EECs has greatly expanded the complexity of EEC endocrinology, with implications for understanding the contribution of EECs to disease pathophysiology. Pubmed searches identified manuscripts highlighting new concepts illuminating the molecular biology, classification and functional role(s) of EECs and their hormonal products. Molecular interrogation of EECs has been transformed over the past decade, raising multiple new questions that challenge historical concepts of EEC biology. Evidence for evolution of the EEC from a unihormonal cell type with classical endocrine actions, to a complex plurihormonal dynamic cell with pleiotropic interactive functional networks within the gastrointestinal mucosa is critically assessed. We discuss gaps in understanding how EECs sense and respond to nutrients, cytokines, toxins, pathogens, the microbiota, and the microbial metabolome, and highlight the expanding translational relevance of EECs in the pathophysiology and therapy of metabolic and inflammatory disorders. The EEC system represents the largest specialized endocrine network in human physiology, integrating environmental and nutrient cues, enabling neural and hormonal control of metabolic homeostasis. Updating EEC classification systems will enable more accurate comparative analyses of EEC subpopulations and endocrine networks in multiple regions of the gastrointestinal tract.

Soil water regulates the control of photosynthesis on diel hysteresis between soil respiration and temperature in a desert shrubland

NASA Astrophysics Data System (ADS)

Wang, Ben; Zha, Tian Shan; Jia, Xin; Gong, Jin Nan; Bourque, Charles; Feng, Wei; Tian, Yun; Wu, Bin; Qing Zhang, Yu; Peltola, Heli

2017-09-01

Explanations for the occurrence of hysteresis (asynchronicity) between diel soil respiration (Rs) and soil temperature (Ts) have evoked both biological and physical mechanisms. The specifics of these explanations, however, tend to vary with the particular ecosystem or biome being investigated. So far, the relative degree of control of biological and physical processes on hysteresis is not clear for drylands. This study examined the seasonal variation in diel hysteresis and its biological control in a desert-shrub ecosystem in northwest (NW) China. The study was based on continuous measurements of Rs, air temperature (Ta), temperature at the soil surface and below (Tsurf and Ts), volumetric soil water content (SWC), and photosynthesis in a dominant desert shrub (i.e., Artemisia ordosica) over an entire year in 2013. Trends in diel Rs were observed to vary with SWC over the growing season (April to October). Diel variations in Rs were more closely associated with variations in Tsurf than with photosynthesis as SWC increased, leading to Rs being in phase with Tsurf, particularly when SWC > 0.08 m3 m-3 (ratio of SWC to soil porosity = 0.26). However, as SWC decreased below 0.08 m3 m-3, diel variations in Rs were more closely related to variations in photosynthesis, leading to pronounced hysteresis between Rs and Tsurf. Incorporating photosynthesis into a Q10-function eliminated 84.2 % of the observed hysteresis, increasing the overall descriptive capability of the function. Our findings highlight a high degree of control by photosynthesis and SWC in regulating seasonal variation in diel hysteresis between Rs and temperature.

Imparting the unique properties of DNA into complex material architectures and functions.

PubMed

Xu, Phyllis F; Noh, Hyunwoo; Lee, Ju Hun; Domaille, Dylan W; Nakatsuka, Matthew A; Goodwin, Andrew P; Cha, Jennifer N

2013-07-01

While the remarkable chemical and biological properties of DNA have been known for decades, these properties have only been imparted into materials with unprecedented function much more recently. The inimitable ability of DNA to form programmable, complex assemblies through stable, specific, and reversible molecular recognition has allowed the creation of new materials through DNA's ability to control a material's architecture and properties. In this review we discuss recent progress in how DNA has brought unmatched function to materials, focusing specifically on new advances in delivery agents, devices, and sensors.

Theoretical foundations for traditional and generalized sensitivity functions for nonlinear delay differential equations.

PubMed

Banks, H Thomas; Robbins, Danielle; Sutton, Karyn L

2013-01-01

In this paper we present new results for differentiability of delay systems with respect to initial conditions and delays. After motivating our results with a wide range of delay examples arising in biology applications, we further note the need for sensitivity functions (both traditional and generalized sensitivity functions), especially in control and estimation problems. We summarize general existence and uniqueness results before turning to our main results on differentiation with respect to delays, etc. Finally we discuss use of our results in the context of estimation problems.

CRISPR: express delivery to any DNA address.

PubMed

Peterson, A

2017-01-01

The sudden emergence and worldwide adoption of CRISPR gene-editing technology confronts humanity with unprecedented opportunities and choices. CRISPR's transformative impact on our future understanding of biology, along with its potential to unleash control over the most fundamental of biological processes, is predictable by already achieved applications. Although its origin, composition, and function were revealed only recently, close to 3000 CRISPR-based publications have appeared including insightful and diversely focused reviews referenced here. Adding further to scientific and public awareness, a recent symposium addressed the ethical implications of interfacing CRISPR technology and human biology. However, the magnitude of CRISPR's rapidly emerging power mandates its broadest assessment. Only with the participation of a diverse and informed community can the most effective and humanity-positive CRISPR applications be defined. This brief review is aimed at those with little previous exposure to the CRISPR revolution. The molecules that constitute CRISPR's core components and their functional organization are described along with how the mechanism has been harnessed to edit genome structure and modulate gene function. Additionally, a glimpse into CRISPR's potential to unleash genetic changes with far-reaching consequences is presented. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

A machine-learned analysis of human gene polymorphisms modulating persisting pain points at major roles of neuroimmune processes.

PubMed

Kringel, Dario; Lippmann, Catharina; Parnham, Michael J; Kalso, Eija; Ultsch, Alfred; Lötsch, Jörn

2018-06-19

Human genetic research has implicated functional variants of more than one hundred genes in the modulation of persisting pain. Artificial intelligence and machine learning techniques may combine this knowledge with results of genetic research gathered in any context, which permits the identification of the key biological processes involved in chronic sensitization to pain. Based on published evidence, a set of 110 genes carrying variants reported to be associated with modulation of the clinical phenotype of persisting pain in eight different clinical settings was submitted to unsupervised machine-learning aimed at functional clustering. Subsequently, a mathematically supported subset of genes, comprising those most consistently involved in persisting pain, was analyzed by means of computational functional genomics in the Gene Ontology knowledgebase. Clustering of genes with evidence for a modulation of persisting pain elucidated a functionally heterogeneous set. The situation cleared when the focus was narrowed to a genetic modulation consistently observed throughout several clinical settings. On this basis, two groups of biological processes, the immune system and nitric oxide signaling, emerged as major players in sensitization to persisting pain, which is biologically highly plausible and in agreement with other lines of pain research. The present computational functional genomics-based approach provided a computational systems-biology perspective on chronic sensitization to pain. Human genetic control of persisting pain points to the immune system as a source of potential future targets for drugs directed against persisting pain. Contemporary machine-learned methods provide innovative approaches to knowledge discovery from previous evidence. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Extracellular matrix functionalized microcavities to control hematopoietic stem and progenitor cell fate.

PubMed

Kurth, Ina; Franke, Katja; Pompe, Tilo; Bornhäuser, Martin; Werner, Carsten

2011-06-14

Polymeric microcavities functionalized with extracellular matrix components were used as an experimental in vitro model to investigate principles of hematopoietic stem and progenitor cell (HSPC) fate control. Using human CD133+ HSPC we could demonstrate distinct differences in HSPC cycling and differentiation dependence on the adhesion ligand specificity (i.e., heparin, collagen I) and cytokine levels. The presented microcavity platform provides a powerful in vitro approach to explore the role of exogenous cues in HSPC fate decisions and can therefore be instrumental to progress in stem cell biology and translational research toward new therapies. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Smart Electrospun Nanofibers for Controlled Drug Release: Recent Advances and New Perspectives

PubMed Central

Weng, Lin; Xie, Jingwei

2017-01-01

In biological systems, chemical molecules or ions often release upon certain conditions, at a specific location, and over a desired period of time. Electrospun nanofibers that undergo alterations in the physicochemical characteristics corresponding to environmental changes have gained considerable interest for various applications. Inspired by biological systems, therapeutic molecules have been integrated with these smart electrospun nanofibers, presenting activation-modulated or feedback-regulated control of drug release. Compared to other materials like smart hydrogels, environment-responsive nanofiber-based drug delivery systems are relatively new but possess incomparable advantages due to their greater permeability, which allows shorter response time and more precise control over the release rate. In this article, we review the mechanisms of various environmental parameters functioning as stimuli to tailor the release rates of smart electrospun nanofibers. We also illustrate several typical examples in specific applications. We conclude this article with a discussion on perspectives and future possibilities in this field. PMID:25732665

Gelatin device for the delivery of growth factors involved in endochondral ossification.

PubMed

Ahrens, Lucas A J; Vonwil, Daniel; Christensen, Jon; Shastri, V Prasad

2017-01-01

Controlled release drug delivery systems are well established as oral and implantable dosage forms. However, the controlled release paradigm can also be used to present complex soluble signals responsible for cellular organization during development. Endochondral ossification (EO), the developmental process of bone formation from a cartilage matrix is controlled by several soluble signals with distinct functions that vary in structure, molecular weight and stability. This makes delivering them from a single vehicle rather challenging. Herein, a gelatin-based delivery system suitable for the delivery of small molecules as well as recombinant human (rh) proteins (rhWNT3A, rhFGF2, rhVEGF, rhBMP4) is reported. The release behavior and biological activity of the released molecules was validated using analytical and biological assays, including cell reporter systems. The simplicity of fabrication of the gelatin device should foster its adaptation by the diverse scientific community interested in interrogating developmental processes, in vivo.

Smart electrospun nanofibers for controlled drug release: recent advances and new perspectives.

PubMed

Weng, Lin; Xie, Jingwei

2015-01-01

In biological systems, chemical molecules or ions often release upon certain conditions, at a specific location, and over a desired period of time. Electrospun nanofibers that undergo alterations in the physicochemical characteristics corresponding to environmental changes have gained considerable interest for various applications. Inspired by biological systems, therapeutic molecules have been integrated with these smart electrospun nanofibers, presenting activation-modulated or feedback-regulated control of drug release. Compared to other materials like smart hydrogels, environment-responsive nanofiber-based drug delivery systems are relatively new but possess incomparable advantages due to their greater permeability, which allows shorter response time and more precise control over the release rate. In this article, we review the mechanisms of various environmental parameters functioning as stimuli to tailor the release rates of smart electrospun nanofibers. We also illustrate several typical examples in specific applications. We conclude this article with a discussion on perspectives and future possibilities in this field.

Gelatin device for the delivery of growth factors involved in endochondral ossification

PubMed Central

Ahrens, Lucas A. J.; Vonwil, Daniel; Christensen, Jon

2017-01-01

Controlled release drug delivery systems are well established as oral and implantable dosage forms. However, the controlled release paradigm can also be used to present complex soluble signals responsible for cellular organization during development. Endochondral ossification (EO), the developmental process of bone formation from a cartilage matrix is controlled by several soluble signals with distinct functions that vary in structure, molecular weight and stability. This makes delivering them from a single vehicle rather challenging. Herein, a gelatin-based delivery system suitable for the delivery of small molecules as well as recombinant human (rh) proteins (rhWNT3A, rhFGF2, rhVEGF, rhBMP4) is reported. The release behavior and biological activity of the released molecules was validated using analytical and biological assays, including cell reporter systems. The simplicity of fabrication of the gelatin device should foster its adaptation by the diverse scientific community interested in interrogating developmental processes, in vivo. PMID:28380024

Tuning the instrument: sonic properties in the spider's web

PubMed Central

Soler, A.; Siviour, C. R.; Zaera, R.; Vollrath, F.

2016-01-01

Spider orb webs are multifunctional, acting to absorb prey impact energy and transmit vibratory information to the spider. This paper explores the links between silk material properties, propagation of vibrations within webs and the ability of the spider to control and balance web function. Combining experimental and modelling approaches, we contrast transverse and longitudinal wave propagation in the web. It emerged that both transverse and longitudinal wave amplitude in the web can be adjusted through changes in web tension and dragline silk stiffness, i.e. properties that can be controlled by the spider. In particular, we propose that dragline silk supercontraction may have evolved as a control mechanism for these multifunctional fibres. The various degrees of active influence on web engineering reveals the extraordinary ability of spiders to shape the physical properties of their self-made materials and architectures to affect biological functionality, balancing trade-offs between structural and sensory functions. PMID:27605164

A Functional Subnetwork Approach to Designing Synthetic Nervous Systems That Control Legged Robot Locomotion

PubMed Central

Szczecinski, Nicholas S.; Hunt, Alexander J.; Quinn, Roger D.

2017-01-01

A dynamical model of an animal’s nervous system, or synthetic nervous system (SNS), is a potentially transformational control method. Due to increasingly detailed data on the connectivity and dynamics of both mammalian and insect nervous systems, controlling a legged robot with an SNS is largely a problem of parameter tuning. Our approach to this problem is to design functional subnetworks that perform specific operations, and then assemble them into larger models of the nervous system. In this paper, we present networks that perform addition, subtraction, multiplication, division, differentiation, and integration of incoming signals. Parameters are set within each subnetwork to produce the desired output by utilizing the operating range of neural activity, R, the gain of the operation, k, and bounds based on biological values. The assembly of large networks from functional subnetworks underpins our recent results with MantisBot. PMID:28848419

Fine-Tuning the Antimicrobial Profile of Biocompatible Gold Nanoparticles by Sequential Surface Functionalization Using Polyoxometalates and Lysine

PubMed Central

Daima, Hemant K.; Selvakannan, P. R.; Shukla, Ravi; Bhargava, Suresh K.; Bansal, Vipul

2013-01-01

Antimicrobial action of nanomaterials is typically assigned to the nanomaterial composition, size and/or shape, whereas influence of complex corona stabilizing the nanoparticle surface is often neglected. We demonstrate sequential surface functionalization of tyrosine-reduced gold nanoparticles (AuNPsTyr) with polyoxometalates (POMs) and lysine to explore controlled chemical functionality-driven antimicrobial activity. Our investigations reveal that highly biocompatible gold nanoparticles can be tuned to be a strong antibacterial agent by fine-tuning their surface properties in a controllable manner. The observation from the antimicrobial studies on a gram negative bacterium Escherichia coli were further validated by investigating the anticancer properties of these step-wise surface-controlled materials against A549 human lung carcinoma cells, which showed a similar toxicity pattern. These studies highlight that the nanomaterial toxicity and biological applicability are strongly governed by their surface corona. PMID:24147146

Fine-tuning the antimicrobial profile of biocompatible gold nanoparticles by sequential surface functionalization using polyoxometalates and lysine.

PubMed

Daima, Hemant K; Selvakannan, P R; Shukla, Ravi; Bhargava, Suresh K; Bansal, Vipul

2013-01-01

Antimicrobial action of nanomaterials is typically assigned to the nanomaterial composition, size and/or shape, whereas influence of complex corona stabilizing the nanoparticle surface is often neglected. We demonstrate sequential surface functionalization of tyrosine-reduced gold nanoparticles (AuNPs(Tyr)) with polyoxometalates (POMs) and lysine to explore controlled chemical functionality-driven antimicrobial activity. Our investigations reveal that highly biocompatible gold nanoparticles can be tuned to be a strong antibacterial agent by fine-tuning their surface properties in a controllable manner. The observation from the antimicrobial studies on a gram negative bacterium Escherichia coli were further validated by investigating the anticancer properties of these step-wise surface-controlled materials against A549 human lung carcinoma cells, which showed a similar toxicity pattern. These studies highlight that the nanomaterial toxicity and biological applicability are strongly governed by their surface corona.

Course 6: Physics of Composite Cell Membrane and Actin Based Cytoskeleton

NASA Astrophysics Data System (ADS)

Sackmann, E.; Bausch, A. R.; Vonna, L.

1 Architecture of composite cell membranes 1.1 The lipid/protein bilayer is a multicomponent smectic phase with mosaic like architecture 1.2 The spectrin/actin cytoskeleton as hyperelastic cell stabilizer 1.3 The actin cortex: Architecture and function 2 Physics of the actin based cytoskeleton 2.1 Actin is a living semiflexible polymer 2.2 Actin network as viscoelastic body 2.3 Correlation between macroscopic viscoelasticity and molecular 3 Heterogeneous actin gels in cells and biological function 3.1 Manipulation of actin gels 3.2 Control of organization and function of actin cortex by cell signalling 4 Micromechanics and microrheometry of cells 5 Activation of endothelial cells: On the possibility of formation of stress fibers as phase transition of actin-network triggered by cell signalling pathways 6 On cells as adaptive viscoplastic bodies 7 Controll of cellular protrusions controlled by actin/myosin cortex

Mitogen-activated protein kinase phosphatase 1 (MKP-1) in macrophage biology and cardiovascular disease. A redox-regulated master controller of monocyte function and macrophage phenotype.

PubMed

Kim, Hong Seok; Asmis, Reto

2017-08-01

MAPK pathways play a critical role in the activation of monocytes and macrophages by pathogens, signaling molecules and environmental cues and in the regulation of macrophage function and plasticity. MAPK phosphatase 1 (MKP-1) has emerged as the main counter-regulator of MAPK signaling in monocytes and macrophages. Loss of MKP-1 in monocytes and macrophages in response to metabolic stress leads to dysregulation of monocyte adhesion and migration, and gives rise to dysfunctional, proatherogenic monocyte-derived macrophages. Here we review the properties of this redox-regulated dual-specificity MAPK phosphatase and the role of MKP-1 in monocyte and macrophage biology and cardiovascular diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Recent development, applications, and perspectives of mesoporous silica particles in medicine and biotechnology.

PubMed

Pasqua, Luigi; Cundari, Sante; Ceresa, Cecilia; Cavaletti, Guido

2009-01-01

Mesoporous silica particles (MSP) are a new development in nanotechnology. Covalent modification of the surface of the silica is possible both on the internal pore and on the external particle surface. It allows the design of functional nanostructured materials with properties of organic, biological and inorganic components. Research and development are ongoing on the MSP, which have applications in catalysis, drug delivery and imaging. The most recent and interesting advancements in size, morphology control and surface functionalization of MSP have enhanced the biocompatibility of these materials with high surface areas and pore volumes. In the last 5 years several reports have demonstrated that MSP can be efficiently internalized using in vitro and animal models. The functionalization of MSP with organic moieties or other nanostructures brings controlled release and molecular recognition capabilities to these mesoporous materials for drug/gene delivery and sensing applications, respectively. Herein, we review recent research progress on the design of functional MSP materials with various mechanisms of targeting and controlled release.

New gene functions in megakaryopoiesis and platelet formation

PubMed Central

Gieger, Christian; Radhakrishnan, Aparna; Cvejic, Ana; Tang, Weihong; Porcu, Eleonora; Pistis, Giorgio; Serbanovic-Canic, Jovana; Elling, Ulrich; Goodall, Alison H.; Labrune, Yann; Lopez, Lorna M.; Mägi, Reedik; Meacham, Stuart; Okada, Yukinori; Pirastu, Nicola; Sorice, Rossella; Teumer, Alexander; Voss, Katrin; Zhang, Weihua; Ramirez-Solis, Ramiro; Bis, Joshua C.; Ellinghaus, David; Gögele, Martin; Hottenga, Jouke-Jan; Langenberg, Claudia; Kovacs, Peter; O’Reilly, Paul F.; Shin, So-Youn; Esko, Tõnu; Hartiala, Jaana; Kanoni, Stavroula; Murgia, Federico; Parsa, Afshin; Stephens, Jonathan; van der Harst, Pim; van der Schoot, C. Ellen; Allayee, Hooman; Attwood, Antony; Balkau, Beverley; Bastardot, François; Basu, Saonli; Baumeister, Sebastian E.; Biino, Ginevra; Bomba, Lorenzo; Bonnefond, Amélie; Cambien, François; Chambers, John C.; Cucca, Francesco; D’Adamo, Pio; Davies, Gail; de Boer, Rudolf A.; de Geus, Eco J. C.; Döring, Angela; Elliott, Paul; Erdmann, Jeanette; Evans, David M.; Falchi, Mario; Feng, Wei; Folsom, Aaron R.; Frazer, Ian H.; Gibson, Quince D.; Glazer, Nicole L.; Hammond, Chris; Hartikainen, Anna-Liisa; Heckbert, Susan R.; Hengstenberg, Christian; Hersch, Micha; Illig, Thomas; Loos, Ruth J. F.; Jolley, Jennifer; Khaw, Kay Tee; Kühnel, Brigitte; Kyrtsonis, Marie-Christine; Lagou, Vasiliki; Lloyd-Jones, Heather; Lumley, Thomas; Mangino, Massimo; Maschio, Andrea; Leach, Irene Mateo; McKnight, Barbara; Memari, Yasin; Mitchell, Braxton D.; Montgomery, Grant W.; Nakamura, Yusuke; Nauck, Matthias; Navis, Gerjan; Nöthlings, Ute; Nolte, Ilja M.; Porteous, David J.; Pouta, Anneli; Pramstaller, Peter P.; Pullat, Janne; Ring, Susan M.; Rotter, Jerome I.; Ruggiero, Daniela; Ruokonen, Aimo; Sala, Cinzia; Samani, Nilesh J.; Sambrook, Jennifer; Schlessinger, David; Schreiber, Stefan; Schunkert, Heribert; Scott, James; Smith, Nicholas L.; Snieder, Harold; Starr, John M.; Stumvoll, Michael; Takahashi, Atsushi; Tang, W. H. Wilson; Taylor, Kent; Tenesa, Albert; Thein, Swee Lay; Tönjes, Anke; Uda, Manuela; Ulivi, Sheila; van Veldhuisen, Dirk J.; Visscher, Peter M.; Völker, Uwe; Wichmann, H.-Erich; Wiggins, Kerri L.; Willemsen, Gonneke; Yang, Tsun-Po; Zhao, Jing Hua; Zitting, Paavo; Bradley, John R.; Dedoussis, George V.; Gasparini, Paolo; Hazen, Stanley L.; Metspalu, Andres; Pirastu, Mario; Shuldiner, Alan R.; van Pelt, L. Joost; Zwaginga, Jaap-Jan; Boomsma, Dorret I.; Deary, Ian J.; Franke, Andre; Froguel, Philippe; Ganesh, Santhi K.; Jarvelin, Marjo-Riitta; Martin, Nicholas G.; Meisinger, Christa; Psaty, Bruce M.; Spector, Timothy D.; Wareham, Nicholas J.; Akkerman, Jan-Willem N.; Ciullo, Marina; Deloukas, Panos; Greinacher, Andreas; Jupe, Steve; Kamatani, Naoyuki; Khadake, Jyoti; Kooner, Jaspal S.; Penninger, Josef; Prokopenko, Inga; Stemple, Derek; Toniolo, Daniela; Wernisch, Lorenz; Sanna, Serena; Hicks, Andrew A.; Rendon, Augusto; Ferreira, Manuel A.; Ouwehand, Willem H.; Soranzo, Nicole

2012-01-01

Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function. PMID:22139419

Systematic design of membership functions for fuzzy-logic control: A case study on one-stage partial nitritation/anammox treatment systems.

PubMed

Boiocchi, Riccardo; Gernaey, Krist V; Sin, Gürkan

2016-10-01

A methodology is developed to systematically design the membership functions of fuzzy-logic controllers for multivariable systems. The methodology consists of a systematic derivation of the critical points of the membership functions as a function of predefined control objectives. Several constrained optimization problems corresponding to different qualitative operation states of the system are defined and solved to identify, in a consistent manner, the critical points of the membership functions for the input variables. The consistently identified critical points, together with the linguistic rules, determine the long term reachability of the control objectives by the fuzzy logic controller. The methodology is highlighted using a single-stage side-stream partial nitritation/Anammox reactor as a case study. As a result, a new fuzzy-logic controller for high and stable total nitrogen removal efficiency is designed. Rigorous simulations are carried out to evaluate and benchmark the performance of the controller. The results demonstrate that the novel control strategy is capable of rejecting the long-term influent disturbances, and can achieve a stable and high TN removal efficiency. Additionally, the controller was tested, and showed robustness, against measurement noise levels typical for wastewater sensors. A feedforward-feedback configuration using the present controller would give even better performance. In comparison, a previously developed fuzzy-logic controller using merely expert and intuitive knowledge performed worse. This proved the importance of using a systematic methodology for the derivation of the membership functions for multivariable systems. These results are promising for future applications of the controller in real full-scale plants. Furthermore, the methodology can be used as a tool to help systematically design fuzzy logic control applications for other biological processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

A detailed observation of the ejection and retraction of defense tissue acontia in sea anemone (Exaiptasia pallida).

PubMed

Lam, Julie; Cheng, Ya-Wen; Chen, Wan-Nan U; Li, Hsing-Hui; Chen, Chii-Shiarng; Peng, Shao-En

2017-01-01

Acontia, located in the gastrovascular cavity of anemone, are thread-like tissue containing numerous stinging cells which serve as a unique defense tissue against predators of the immobile acontiarian sea anemone. Although its morphology and biological functions, such as defense and digestion, have been studied, the defense behavior and the specific events of acontia ejection and retraction are unclear. The aim of this study is to observe and record the detailed process of acontia control in anemones. Observations reveal that the anemone, Exaiptasia pallida , possibly controls a network of body muscles and manipulates water pressure in the gastrovascular cavity to eject and retract acontia. Instead of resynthesizing acontia after each ejection, the retraction and reuse of acontia enables the anemone to respond quickly at any given time, thus increasing its overall survivability. Since the Exaiptasia anemone is an emerging model for coral biology, this study provides a foundation to further investigate the biophysics, neuroscience, and defense biology of this marine model organism.

A detailed observation of the ejection and retraction of defense tissue acontia in sea anemone (Exaiptasia pallida)

PubMed Central

Lam, Julie; Cheng, Ya-Wen; Chen, Wan-Nan U.; Li, Hsing-Hui; Chen, Chii-Shiarng

2017-01-01

Acontia, located in the gastrovascular cavity of anemone, are thread-like tissue containing numerous stinging cells which serve as a unique defense tissue against predators of the immobile acontiarian sea anemone. Although its morphology and biological functions, such as defense and digestion, have been studied, the defense behavior and the specific events of acontia ejection and retraction are unclear. The aim of this study is to observe and record the detailed process of acontia control in anemones. Observations reveal that the anemone, Exaiptasia pallida, possibly controls a network of body muscles and manipulates water pressure in the gastrovascular cavity to eject and retract acontia. Instead of resynthesizing acontia after each ejection, the retraction and reuse of acontia enables the anemone to respond quickly at any given time, thus increasing its overall survivability. Since the Exaiptasia anemone is an emerging model for coral biology, this study provides a foundation to further investigate the biophysics, neuroscience, and defense biology of this marine model organism. PMID:28243530

Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.

PubMed

Ambrosio, Maria R; Rocca, Bruno J; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T; Tripodi, Sergio A; Tosi, Piero

2015-01-01

Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.

Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma

PubMed Central

Ambrosio, Maria R.; Rocca, Bruno J.; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T.; Tripodi, Sergio A.; Tosi, Piero

2015-01-01

Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis. PMID:26425551

Subjective Cognitive Complaints and Functional Disability in Patients With Borderline Personality Disorder and Their Nonaffected First-Degree Relatives

PubMed Central

Ruocco, Anthony C; Lam, Jaeger; McMain, Shelley F

2014-01-01

Objective: To examine the contributions of subjective cognitive complaints to functional disability in patients with borderline personality disorder (BPD) and their nonaffected relatives. Method: Patients with BPD (n = 26), their first-degree biological relatives (n = 17), and nonpsychiatric control subjects (n = 31) completed a self-report measure of cognitive difficulties and rated the severity of their functional disability on the World Health Organization Disability Assessment Schedule 2.0. Results: After accounting for group differences in age and severity of depressive symptoms, patients and relatives endorsed more inattention and memory problems than control subjects. Whereas probands reported greater disability than relatives and control subjects across all functional domains, relatives described more difficulties than control subjects in managing multiple life activities, including domestic activities and occupational and academic functioning, and participating in society. For both probands and relatives, inattention and memory problems were linked primarily to difficulties with life activities, independent of depression and other comorbid psychiatric disorders. Conclusions: Problems with inattention and forgetfulness may lead to difficulties carrying out activities of daily living and occupational or academic problems in patients with BPD, as well as their nonaffected first-degree relatives. PMID:25007408

Subjective cognitive complaints and functional disability in patients with borderline personality disorder and their nonaffected first-degree relatives.

PubMed

Ruocco, Anthony C; Lam, Jaeger; McMain, Shelley F

2014-06-01

To examine the contributions of subjective cognitive complaints to functional disability in patients with borderline personality disorder (BPD) and their nonaffected relatives. Patients with BPD (n = 26), their first-degree biological relatives (n = 17), and nonpsychiatric control subjects (n = 31) completed a self-report measure of cognitive difficulties and rated the severity of their functional disability on the World Health Organization Disability Assessment Schedule 2.0. After accounting for group differences in age and severity of depressive symptoms, patients and relatives endorsed more inattention and memory problems than control subjects. Whereas probands reported greater disability than relatives and control subjects across all functional domains, relatives described more difficulties than control subjects in managing multiple life activities, including domestic activities and occupational and academic functioning, and participating in society. For both probands and relatives, inattention and memory problems were linked primarily to difficulties with life activities, independent of depression and other comorbid psychiatric disorders. Problems with inattention and forgetfulness may lead to difficulties carrying out activities of daily living and occupational or academic problems in patients with BPD, as well as their nonaffected first-degree relatives.

Size-controlled synthesis, surface functionalization, and biological applications of thiol-organosilica particles.

PubMed

Nakamura, Michihiro; Ozaki, Shuji; Abe, Masahiro; Doi, Hiroyuki; Matsumoto, Toshio; Ishimura, Kazunori

2010-08-01

Thiol-organosilica particles of a narrow size distribution, made from 3-mercaptopropyltrimethoxysilane (MPMS), were prepared by means of a one-pot synthesis. We examined three synthetic conditions at high temperature (100 degrees C), including the Stöber synthesis and two entirely aqueous syntheses. Under all conditions, the sizes of MPMS particles were well controlled, and the average of the coefficient of variation for the size distribution was less than 20%. The incubation times required for formation of MPMS particles were shorter at high temperature than at low temperature. MPMS particles internally functionalized with fluorescent dye were also prepared by means of the same one-pot synthesis. On flow cytometry analysis these MPMS particles showed distinct peaks of scattering due to well-controlled sizes of particles as well as due to fluorescence signals. Real-time observation of interaction between fluorescent MPMPS particles and cultured cells could be observed under fluorescent microscopy with bright light. The surface of the as-prepared MPMS particles contained exposed mercaptopropyl residues, and the ability to adsorb proteins was at least 6 times higher than that of gold nanopaticles. In addition, fluorescein-labeled proteins adsorbed to the surface of the particles were quantitatively detected at the pg/ml level by flow cytometry. MPMS particles surface functionalized with anti-CD20 antibody using adsorption could bind with lymphoma cells expressing CD20 specifically. In this paper, we demonstrated the possibility of size-controlled thiol-organosilica particles for wild range of biological applications. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

KEEPING AN EYE ON RETINOBLASTOMA CONTROL OF HUMAN EMBRYONIC STEM CELLS

PubMed Central

Conklin, Jamie F.; Sage, Julien

2010-01-01

Human embryonic stem cells (hESCs) hold great promise in regenerative medicine. However, before the full potential of these cells is achieved, major basic biological questions need to be addressed. In particular, there are still gaps in our knowledge of the molecular mechanisms underlying the derivation of hESCs from blastocysts, the regulation of the undifferentiated, pluripotent state, and the control of differentiation into specific lineages. Furthermore, we still do not fully understand the tumorigenic potential of hESCs, limiting their use in regenerative medicine. The RB pathway is a key signaling module that controls cellular proliferation, cell survival, chromatin structure, and cellular differentiation in mammalian cells. Members of the RB pathway are important regulators of hESC biology and manipulation of the activity of this pathway may provide novel means to control the fate of hESCs. Here we review what is known about the expression and function of members of the RB pathway in hESCs and discuss areas of interest in this field. PMID:19760644

Programmable temperature control system for biological materials

NASA Technical Reports Server (NTRS)

Anselmo, V. J.; Harrison, R. G.; Rinfret, A. P.

1982-01-01

A system was constructed which allows programmable temperature-time control for a 5 cu cm sample volume of arbitrary biological material. The system also measures the parameters necessary for the determination of the sample volume specific heat and thermal conductivity as a function of temperature, and provides a detailed measurement of the temperature during phase change and a means of calculating the heat of the phase change. Steady-state and dynamic temperature control is obtained by supplying heat to the sample volume through resistive elements constructed as an integral part of the sample container. For cooling purposes, this container is totally immersed into a cold heat sink. Using a mixture of dry ice and alcohol at 79 C, the sample volume can be controlled from +40 to -60 C at rates from steady state to + or - 65 C/min. Steady-state temperature precision is better than 0.2 C, while the dynamic capability depends on the temperature rate of change as well as the mass of both the sample and the container.

NAMPT and NAMPT-controlled NAD Metabolism in Vascular Repair.

PubMed

Wang, Pei; Li, Wen-Lin; Liu, Jian-Min; Miao, Chao-Yu

2016-06-01

Vascular repair plays important roles in postischemic remodeling and rehabilitation in cardiovascular and cerebrovascular disease, such as stroke and myocardial infarction. Nicotinamide adenine dinucleotide (NAD), a well-known coenzyme involved in electron transport chain for generation of adenosine triphosphate, has emerged as an important controller regulating various biological signaling pathways. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme for NAD biosynthesis in mammals. NAMPT may also act in a nonenzymatic manner, presumably mediated by unknown receptor(s). Rapidly accumulating data in the past decade show that NAMPT and NAMPT-controlled NAD metabolism regulate fundamental biological functions in endothelial cells, vascular smooth muscle cells, and endothelial progenitor cells. The NAD-consuming proteins, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38, may contribute to the regulatory effects of NAMPT-NAD axis in these cells and vascular repair. This review discusses the current data regarding NAMPT and NAMPT-controlled NAD metabolism in vascular repair and the clinical potential translational application of NAMPT-related products in treatment of cardiovascular and cerebrovascular disease.

A decade and a half of protein intrinsic disorder: Biology still waits for physics

PubMed Central

Uversky, Vladimir N

2013-01-01

The abundant existence of proteins and regions that possess specific functions without being uniquely folded into unique 3D structures has become accepted by a significant number of protein scientists. Sequences of these intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) are characterized by a number of specific features, such as low overall hydrophobicity and high net charge which makes these proteins predictable. IDPs/IDPRs possess large hydrodynamic volumes, low contents of ordered secondary structure, and are characterized by high structural heterogeneity. They are very flexible, but some may undergo disorder to order transitions in the presence of natural ligands. The degree of these structural rearrangements varies over a very wide range. IDPs/IDPRs are tightly controlled under the normal conditions and have numerous specific functions that complement functions of ordered proteins and domains. When lacking proper control, they have multiple roles in pathogenesis of various human diseases. Gaining structural and functional information about these proteins is a challenge, since they do not typically “freeze” while their “pictures are taken.” However, despite or perhaps because of the experimental challenges, these fuzzy objects with fuzzy structures and fuzzy functions are among the most interesting targets for modern protein research. This review briefly summarizes some of the recent advances in this exciting field and considers some of the basic lessons learned from the analysis of physics, chemistry, and biology of IDPs. PMID:23553817

Informational Closed-Loop Coding-Decoding Control Concept as the Base of the Living or Organized Systems Theory

NASA Astrophysics Data System (ADS)

Kirvelis, Dobilas; Beitas, Kastytis

2008-10-01

The aim of this work is to show that the essence of life and living systems is their organization as bioinformational technology on the base of informational anticipatory control. Principal paradigmatic and structural schemes of functional organization of life (organisms and their systems) are constructed on the basis of systemic analysis and synthesis of main phenomenological features of living world. Life is based on functional elements that implement engineering procedures of closed-loop coding-decoding control (CL-CDC). Phenomenon of natural bioinformational control appeared and developed on the Earth 3-4 bln years ago, when the life originated as a result of chemical and later biological evolution. Informatics paradigm considers the physical and chemical transformations of energy and matter in organized systems as flows that are controlled and the signals as means for purposive informational control programs. The social and technical technological systems as informational control systems are a latter phenomenon engineered by man. The information emerges in organized systems as a necessary component of control technology. Generalized schemes of functional organization on levels of cell, organism and brain neocortex, as the highest biosystem with CL-CDC, are presented. CL-CDC concept expands the understanding of bioinformatics.

The TiPS/TINS lecture: the molecular biology of mammalian glutamate receptor channels.

PubMed

Seeburg, P H

1993-08-01

In native brain membranes the principal excitatory neurotransmitter L-glutamate activates cation-conducting channels with distinct biophysical and pharmacological properties. Molecular cloning has revealed the existence of 16 channel subunits that can assemble in homomeric or heteromeric configurations in vitro to form receptor channels with disparate functional properties. This review describes the different channel types obtained by recombinant means and the genetic mechanisms controlling the expression of functionally important channel structures.

The TINS/TiPS Lecture. The molecular biology of mammalian glutamate receptor channels.

PubMed

Seeburg, P H

1993-09-01

In native brain membranes the principal excitatory neurotransmitter L-glutamate activates cation-conducting channels with distinct biophysical and pharmacological properties. Molecular cloning has revealed the existence of 16 channel subunits that can assemble in homomeric or heteromeric configurations in vitro to form receptor channels with disparate functional properties. This review describes the different channel types obtained by recombinant means and the genetic mechanisms controlling the expression of functionally important channel structures.

Functional Proteomic Analysis of Signaling Networks and Response to Targeted Therapy

DTIC Science & Technology

2009-03-01

of biological networks. Nature Biotechnology, 23(9):961–966, 2005. [18] A. Ma’ayan, S. L Jenkins, S. Neves, A. Hasseldine, E. Grace, B . Dubin-Thaler...functions of biochemical networks. Trends Biochemical Sci 31: 284–291. 56. Blinov ML, Faeder JR, Goldstein B , Hlavacek WS (2006) A network model of early...mean intensity value, red - increased intensity of signal and green - decreased intensity of signal. Lap- Lapatinib, Das- Dasatinib, C-control, A& B

Transcriptomic Profiling and Functional Characterization of Fusion Genes in Recurrent Ovarian Cancer

DTIC Science & Technology

2017-09-01

the enhanced malignancy observed in recurrent disease. In the first year of this proposal we have assembled a cohort of 18 patient matched pairs of...significance and biologic function of prioritized RNA fusion events. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 ...cellularity. 19 cases were identified (Table 1) but one was removed for quality control issues thus leaving a total of 18 cases. Table 1 shows the clinical

Functions in Biological Kind Classification

ERIC Educational Resources Information Center

Lombrozo, Tania; Rehder, Bob

2012-01-01

Biological traits that serve functions, such as a zebra's coloration (for camouflage) or a kangaroo's tail (for balance), seem to have a special role in conceptual representations for biological kinds. In five experiments, we investigate whether and why functional features are privileged in biological kind classification. Experiment 1…

What is the role of curvature on the properties of nanomaterials for biomedical applications?

PubMed

Gonzalez Solveyra, Estefania; Szleifer, Igal

2016-05-01

The use of nanomaterials for drug delivery and theranostics applications is a promising paradigm in nanomedicine, as it brings together the best features of nanotechnolgy, molecular biology, and medicine. To fully exploit the synergistic potential of such interdisciplinary strategy, a comprehensive description of the interactions at the interface between nanomaterials and biological systems is not only crucial, but also mandatory. Routine strategies to engineer nanomaterial-based drugs comprise modifying their surface with biocompatible and targeting ligands, in many cases resorting to modular approaches that assume additive behavior. However, emergent behavior can be observed when combining confinement and curvature. The final properties of functionalized nanomaterials become dependent not only on the properties of their constituents but also on the geometry of the nano-bio interface, and on the local molecular environment. Modularity no longer holds, and the coupling between interactions, chemical equilibrium, and molecular organization has to be directly addressed in order to design smart nanomaterials with controlled spatial functionalization envisioning optimized biomedical applications. Nanoparticle's curvature becomes an integral part of the design strategy, enabling to control and engineer the chemical and surface properties with molecular precision. Understanding how nanoparticle size, morphology, and surface chemistry are interrelated will put us one step closer to engineering nanobiomaterials capable of mimicking biological structures and their behaviors, paving the way into applications and the possibility to elucidate the use of curvature by biological systems. WIREs Nanomed Nanobiotechnol 2016, 8:334-354. doi: 10.1002/wnan.1365 For further resources related to this article, please visit the WIREs website. © 2015 Wiley Periodicals, Inc.

Biological effects due to weak magnetic field on plants

NASA Astrophysics Data System (ADS)

Belyavskaya, N. A.

2004-01-01

Throughout the evolution process, Earth's magnetic field (MF, about 50 μT) was a natural component of the environment for living organisms. Biological objects, flying on planned long-term interplanetary missions, would experience much weaker magnetic fields, since galactic MF is known to be 0.1-1 nT. However, the role of weak magnetic fields and their influence on functioning of biological organisms are still insufficiently understood, and is actively studied. Numerous experiments with seedlings of different plant species placed in weak magnetic field have shown that the growth of their primary roots is inhibited during early germination stages in comparison with control. The proliferative activity and cell reproduction in meristem of plant roots are reduced in weak magnetic field. Cell reproductive cycle slows down due to the expansion of G 1 phase in many plant species (and of G 2 phase in flax and lentil roots), while other phases of cell cycle remain relatively stabile. In plant cells exposed to weak magnetic field, the functional activity of genome at early pre-replicate period is shown to decrease. Weak magnetic field causes intensification of protein synthesis and disintegration in plant roots. At ultrastructural level, changes in distribution of condensed chromatin and nucleolus compactization in nuclei, noticeable accumulation of lipid bodies, development of a lytic compartment (vacuoles, cytosegresomes and paramural bodies), and reduction of phytoferritin in plastids in meristem cells were observed in pea roots exposed to weak magnetic field. Mitochondria were found to be very sensitive to weak magnetic field: their size and relative volume in cells increase, matrix becomes electron-transparent, and cristae reduce. Cytochemical studies indicate that cells of plant roots exposed to weak magnetic field show Ca 2+ over-saturation in all organelles and in cytoplasm unlike the control ones. The data presented suggest that prolonged exposures of plants to weak magnetic field may cause different biological effects at the cellular, tissue and organ levels. They may be functionally related to systems that regulate plant metabolism including the intracellular Ca 2+ homeostasis. However, our understanding of very complex fundamental mechanisms and sites of interactions between weak magnetic fields and biological systems is still incomplete and still deserve strong research efforts.

Self-assembled materials and supramolecular chemistry within microfluidic environments: from common thermodynamic states to non-equilibrium structures.

PubMed

Sevim, S; Sorrenti, A; Franco, C; Furukawa, S; Pané, S; deMello, A J; Puigmartí-Luis, J

2018-05-01

Self-assembly is a crucial component in the bottom-up fabrication of hierarchical supramolecular structures and advanced functional materials. Control has traditionally relied on the use of encoded building blocks bearing suitable moieties for recognition and interaction, with targeting of the thermodynamic equilibrium state. On the other hand, nature leverages the control of reaction-diffusion processes to create hierarchically organized materials with surprisingly complex biological functions. Indeed, under non-equilibrium conditions (kinetic control), the spatio-temporal command of chemical gradients and reactant mixing during self-assembly (the creation of non-uniform chemical environments for example) can strongly affect the outcome of the self-assembly process. This directly enables a precise control over material properties and functions. In this tutorial review, we show how the unique physical conditions offered by microfluidic technologies can be advantageously used to control the self-assembly of materials and of supramolecular aggregates in solution, making possible the isolation of intermediate states and unprecedented non-equilibrium structures, as well as the emergence of novel functions. Selected examples from the literature will be used to confirm that microfluidic devices are an invaluable toolbox technology for unveiling, understanding and steering self-assembly pathways to desired structures, properties and functions, as well as advanced processing tools for device fabrication and integration.

Diverse Supramolecular Nanofiber Networks Assembled by Functional Low-Complexity Domains.

PubMed

An, Bolin; Wang, Xinyu; Cui, Mengkui; Gui, Xinrui; Mao, Xiuhai; Liu, Yan; Li, Ke; Chu, Cenfeng; Pu, Jiahua; Ren, Susu; Wang, Yanyi; Zhong, Guisheng; Lu, Timothy K; Liu, Cong; Zhong, Chao

2017-07-25

Self-assembling supramolecular nanofibers, common in the natural world, are of fundamental interest and technical importance to both nanotechnology and materials science. Despite important advances, synthetic nanofibers still lack the structural and functional diversity of biological molecules, and the controlled assembly of one type of molecule into a variety of fibrous structures with wide-ranging functional attributes remains challenging. Here, we harness the low-complexity (LC) sequence domain of fused in sarcoma (FUS) protein, an essential cellular nuclear protein with slow kinetics of amyloid fiber assembly, to construct random copolymer-like, multiblock, and self-sorted supramolecular fibrous networks with distinct structural features and fluorescent functionalities. We demonstrate the utilities of these networks in the templated, spatially controlled assembly of ligand-decorated gold nanoparticles, quantum dots, nanorods, DNA origami, and hybrid structures. Owing to the distinguishable nanoarchitectures of these nanofibers, this assembly is structure-dependent. By coupling a modular genetic strategy with kinetically controlled complex supramolecular self-assembly, we demonstrate that a single type of protein molecule can be used to engineer diverse one-dimensional supramolecular nanostructures with distinct functionalities.

A circannual clock drives expression of genes central for seasonal reproduction.

PubMed

Sáenz de Miera, Cristina; Monecke, Stefanie; Bartzen-Sprauer, Julien; Laran-Chich, Marie-Pierre; Pévet, Paul; Hazlerigg, David G; Simonneaux, Valérie

2014-07-07

Animals living in temperate zones anticipate seasonal environmental changes to adapt their biological functions, especially reproduction and metabolism. Two main physiological mechanisms have evolved for this adaptation: intrinsic long-term timing mechanisms with an oscillating period of approximately 1 year, driven by a circannual clock [1], and synchronization of biological rhythms to the sidereal year using day length (photoperiod) [2]. In mammals, the pineal hormone melatonin relays photoperiodic information to the hypothalamus to control seasonal physiology through well-defined mechanisms [3-6]. In contrast, little is known about how the circannual clock drives endogenous changes in seasonal functions. The aim of this study was to determine whether genes involved in photoperiodic time measurement (TSHβ and Dio2) and central control of reproduction (Rfrp and Kiss1) display circannual rhythms in expression under constant conditions. Male European hamsters, deprived of seasonal time cues by pinealectomy and maintenance in constant photoperiod, were selected when expressing a subjective summer or subjective winter state in their circannual cycle of body weight, temperature, and testicular size. TSHβ expression in the pars tuberalis (PT) displayed a robust circannual variation with highest level in the subjective summer state, which was positively correlated with hypothalamic Dio2 and Rfrp expression. The negative sex steroid feedback was found to act specifically on arcuate Kiss1 expression. Our findings reveal TSH as a circannual output of the PT, which in turn regulates hypothalamic neurons controlling reproductive activity. Therefore, both the circannual and the melatonin signals converge on PT TSHβ expression to synchronize seasonal biological activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

DNA-controlled dynamic colloidal nanoparticle systems for mediating cellular interaction

NASA Astrophysics Data System (ADS)

Ohta, Seiichi; Glancy, Dylan; Chan, Warren C. W.

2016-02-01

Precise control of biosystems requires development of materials that can dynamically change physicochemical properties. Inspired by the ability of proteins to alter their conformation to mediate function, we explored the use of DNA as molecular keys to assemble and transform colloidal nanoparticle systems. The systems consist of a core nanoparticle surrounded by small satellites, the conformation of which can be transformed in response to DNA via a toe-hold displacement mechanism. The conformational changes can alter the optical properties and biological interactions of the assembled nanosystem. Photoluminescent signal is altered by changes in fluorophore-modified particle distance, whereas cellular targeting efficiency is increased 2.5 times by changing the surface display of targeting ligands. These concepts provide strategies for engineering dynamic nanotechnology systems for navigating complex biological environments.

Behavioral Objectives, Science Processes, and Learning from Inquiry-Oriented Instructional Materials.

ERIC Educational Resources Information Center

Anderson, Elaine J.; And Others

Investigated was the effect of systematically combined high and low level cognitive objectives upon the acquisition of science learning. An instructional unit based on a Biological Sciences Curriculum Study (BSCS) Inquiry Slide Set (structure and function, control of blood sugar, a homeostatic mechanism) was chosen because it included stimuli for…

Cognitive Functions of the Cerebellum Explain How Ericsson's Deliberate Practice Produces Giftedness

ERIC Educational Resources Information Center

Vandervert, Larry R.

2007-01-01

A critical issue for Ericsson et al.'s proposal is the development of a fully adequate description of neurophysiological substrates for deliberate practice. Ericsson et al. do provide two substantial subsections on biological substrates--namely, their subsections, "Acquisition of superior power, control, and speed of motor activities" and…

Species identities, not functional groups, explain the effects of earthworms on litter carbon-derived soil respiration

USDA-ARS?s Scientific Manuscript database

Soil respiration is frequently measured as a surrogate for biological activities and is important in soil carbon cycling. The heterotrophic component of soil respiration is primarily driven by microbial decomposition of leaf litter and soil organic matter, and is partially controlled by resource ava...

Genome-Wide Prediction of Intrinsic Disorder; Sequence Alignment of Intrinsically Disordered Proteins

ERIC Educational Resources Information Center

Midic, Uros

2012-01-01

Intrinsic disorder (ID) is defined as a lack of stable tertiary and/or secondary structure under physiological conditions in vitro. Intrinsically disordered proteins (IDPs) are highly abundant in nature. IDPs possess a number of crucial biological functions, being involved in regulation, recognition, signaling and control, e.g. their functional…

Ghrelin stimulates growth hormone release from the pituitary via hypothalamic growth hormone-releasing hormone neurons in the cichlid, Oreochromis niloticus

USDA-ARS?s Scientific Manuscript database

Ghrelin, a gastric peptide, is implicated in a multiplicity of biological functions, including energy homeostasis and reproduction. Neuronal systems that are involved in energy homeostasis as well as reproduction traverse the hypothalamus, however, the mechanism by which they control energy homeosta...

77 FR 12508 - Schedules of Controlled Substances: Placement of Five Synthetic Cannabinoids Into Schedule I

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-01

... Final Order, a ``cannabinoid'' is a class of chemical compounds in the marijuana \\3\\ plant that are... constituent of marijuana. ``Synthetic cannabinoids'' are a large family of chemically unrelated structures functionally (biologically) similar to THC, the active principal of marijuana. \\3\\ Note that ``marihuana'' is...

Systems Genetics Analysis of Genome-Wide Association Study Reveals Novel Associations Between Key Biological Processes and Coronary Artery Disease.

PubMed

Ghosh, Sujoy; Vivar, Juan; Nelson, Christopher P; Willenborg, Christina; Segrè, Ayellet V; Mäkinen, Ville-Petteri; Nikpay, Majid; Erdmann, Jeannette; Blankenberg, Stefan; O'Donnell, Christopher; März, Winfried; Laaksonen, Reijo; Stewart, Alexandre F R; Epstein, Stephen E; Shah, Svati H; Granger, Christopher B; Hazen, Stanley L; Kathiresan, Sekar; Reilly, Muredach P; Yang, Xia; Quertermous, Thomas; Samani, Nilesh J; Schunkert, Heribert; Assimes, Themistocles L; McPherson, Ruth

2015-07-01

Genome-wide association studies have identified multiple genetic variants affecting the risk of coronary artery disease (CAD). However, individually these explain only a small fraction of the heritability of CAD and for most, the causal biological mechanisms remain unclear. We sought to obtain further insights into potential causal processes of CAD by integrating large-scale GWA data with expertly curated databases of core human pathways and functional networks. Using pathways (gene sets) from Reactome, we carried out a 2-stage gene set enrichment analysis strategy. From a meta-analyzed discovery cohort of 7 CAD genome-wide association study data sets (9889 cases/11 089 controls), nominally significant gene sets were tested for replication in a meta-analysis of 9 additional studies (15 502 cases/55 730 controls) from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) Consortium. A total of 32 of 639 Reactome pathways tested showed convincing association with CAD (replication P<0.05). These pathways resided in 9 of 21 core biological processes represented in Reactome, and included pathways relevant to extracellular matrix (ECM) integrity, innate immunity, axon guidance, and signaling by PDRF (platelet-derived growth factor), NOTCH, and the transforming growth factor-β/SMAD receptor complex. Many of these pathways had strengths of association comparable to those observed in lipid transport pathways. Network analysis of unique genes within the replicated pathways further revealed several interconnected functional and topologically interacting modules representing novel associations (eg, semaphoring-regulated axonal guidance pathway) besides confirming known processes (lipid metabolism). The connectivity in the observed networks was statistically significant compared with random networks (P<0.001). Network centrality analysis (degree and betweenness) further identified genes (eg, NCAM1, FYN, FURIN, etc) likely to play critical roles in the maintenance and functioning of several of the replicated pathways. These findings provide novel insights into how genetic variation, interpreted in the context of biological processes and functional interactions among genes, may help define the genetic architecture of CAD. © 2015 American Heart Association, Inc.

Closed-loop control of cellular functions using combinatory drugs guided by a stochastic search algorithm

PubMed Central

Wong, Pak Kin; Yu, Fuqu; Shahangian, Arash; Cheng, Genhong; Sun, Ren; Ho, Chih-Ming

2008-01-01

A mixture of drugs is often more effective than using a single effector. However, it is extremely challenging to identify potent drug combinations by trial and error because of the large number of possible combinations and the inherent complexity of the underlying biological network. With a closed-loop optimization modality, we experimentally demonstrate effective searching for potent drug combinations for controlling cellular functions through a large parametric space. Only tens of iterations out of one hundred thousand possible trials were needed to determine a potent combination of drugs for inhibiting vesicular stomatitis virus infection of NIH 3T3 fibroblasts. In addition, the drug combination reduced the required dosage by ≈10-fold compared with individual drugs. In another example, a potent mixture was identified in thirty iterations out of a possible million combinations of six cytokines that regulate the activity of nuclear factor kappa B in 293T cells. The closed-loop optimization approach possesses the potential of being an effective approach for manipulating a wide class of biological systems. PMID:18356295

Cellular control lies in the balance of forces

NASA Technical Reports Server (NTRS)

Chicurel, M. E.; Chen, C. S.; Ingber, D. E.

1998-01-01

Mechanical tension generated within the cytoskeleton of living cells is emerging as a critical regulator of biological function in diverse situations ranging from the control of chromosome movement to the morphogenesis of the vertebrate brain. In this article, we review recent advances that have been made in terms of understanding how cells generate, transmit and sense mechanical tension, as well as how they use these forces to control their shape and behavior. An integrated view of cell regulation that incorporates mechanics and structure as well as chemistry is beginning to emerge.

Using Synthetic Biology to Engineer Living Cells That Interface with Programmable Materials.

PubMed

Heyde, Keith C; Scott, Felicia Y; Paek, Sung-Ho; Zhang, Ruihua; Ruder, Warren C

2017-03-09

We have developed an abiotic-biotic interface that allows engineered cells to control the material properties of a functionalized surface. This system is made by creating two modules: a synthetically engineered strain of E. coli cells and a functionalized material interface. Within this paper, we detail a protocol for genetically engineering selected behaviors within a strain of E. coli using molecular cloning strategies. Once developed, this strain produces elevated levels of biotin when exposed to a chemical inducer. Additionally, we detail protocols for creating two different functionalized surfaces, each of which is able to respond to cell-synthesized biotin. Taken together, we present a methodology for creating a linked, abiotic-biotic system that allows engineered cells to control material composition and assembly on nonliving substrates.

[Study on an Exoskeleton Hand Function Training Device].

PubMed

Hu, Xin; Zhang, Ying; Li, Jicai; Yi, Jinhua; Yu, Hongliu; He, Rongrong

2016-02-01

Based on the structure and motion bionic principle of the normal adult fingers, biological characteristics of human hands were analyzed, and a wearable exoskeleton hand function training device for the rehabilitation of stroke patients or patients with hand trauma was designed. This device includes the exoskeleton mechanical structure and the electromyography (EMG) control system. With adjustable mechanism, the device was capable to fit different finger lengths, and by capturing the EMG of the users' contralateral limb, the motion state of the exoskeleton hand was controlled. Then driven by the device, the user's fingers conducting adduction/abduction rehabilitation training was carried out. Finally, the mechanical properties and training effect of the exoskeleton hand were verified through mechanism simulation and the experiments on the experimental prototype of the wearable exoskeleton hand function training device.

Magnetoencephalography Study of Right Parietal Lobe Dysfunction of the Evoked Mirror Neuron System in Antipsychotic-Free Schizophrenia

PubMed Central

Kato, Yutaka; Muramatsu, Taro; Kato, Motoichiro; Shibukawa, Yoshiyuki; Shintani, Masuro; Mimura, Masaru

2011-01-01

Introduction Patients with schizophrenia commonly exhibit deficits of non-verbal communication in social contexts, which may be related to cognitive dysfunction that impairs recognition of biological motion. Although perception of biological motion is known to be mediated by the mirror neuron system, there have been few empirical studies of this system in patients with schizophrenia. Methods Using magnetoencephalography, we examined whether antipsychotic-free schizophrenia patients displayed mirror neuron system dysfunction during observation of biological motion (jaw movement of another individual). Results Compared with normal controls, the patients with schizophrenia had fewer components of both the waveform and equivalent current dipole, suggesting aberrant brain activity resulting from dysfunction of the right inferior parietal cortex. They also lacked the changes of alpha band and gamma band oscillation seen in normal controls, and had weaker phase-locking factors and gamma-synchronization predominantly in right parietal cortex. Conclusions Our findings demonstrate that untreated patients with schizophrenia exhibit aberrant mirror neuron system function based on the right inferior parietal cortex, which is characterized by dysfunction of gamma-synchronization in the right parietal lobe during observation of biological motion. PMID:22132217

GP96 is a GARP chaperone and controls regulatory T cell functions.

PubMed

Zhang, Yongliang; Wu, Bill X; Metelli, Alessandra; Thaxton, Jessica E; Hong, Feng; Rachidi, Saleh; Ansa-Addo, Ephraim; Sun, Shaoli; Vasu, Chenthamarakshan; Yang, Yi; Liu, Bei; Li, Zihai

2015-02-01

Molecular chaperones control a multitude of cellular functions via folding chaperone-specific client proteins. CD4+FOXP3+ Tregs play key roles in maintaining peripheral tolerance, which is subject to regulation by multiple molecular switches, including mTOR and hypoxia-inducible factor. It is not clear whether GP96 (also known as GRP94), which is a master TLR and integrin chaperone, controls Treg function. Using murine genetic models, we demonstrated that GP96 is required for Treg maintenance and function, as loss of GP96 resulted in instability of the Treg lineage and impairment of suppressive functions in vivo. In the absence of GP96, Tregs were unable to maintain FOXP3 expression levels, resulting in systemic accumulation of pathogenic IFN-γ-producing and IL-17-producing T cells. We determined that GP96 serves as an essential chaperone for the cell-surface protein glycoprotein A repetitions predominant (GARP), which is a docking receptor for latent membrane-associated TGF-β (mLTGF-β). The loss of both GARP and integrins on GP96-deficient Tregs prevented expression of mLTGF-β and resulted in inefficient production of active TGF-β. Our work demonstrates that GP96 regulates multiple facets of Treg biology, thereby placing Treg stability and immunosuppressive functions strategically under the control of a major stress chaperone.

Indirect nontarget effects of host-specific biological control agents: Implications for biological control

Treesearch

Dean E. Pearson; Ragan M. Callaway

2005-01-01

Classical biological control of weeds currently operates under the assumption that biological control agents are safe (i.e., low risk) if they do not directly attack nontarget species. However, recent studies indicate that even highly host-specific biological control agents can impact nontarget species through indirect effects. This finding has profound...

(Im)Perfect robustness and adaptation of metabolic networks subject to metabolic and gene-expression regulation: marrying control engineering with metabolic control analysis.

PubMed

He, Fei; Fromion, Vincent; Westerhoff, Hans V

2013-11-21

Metabolic control analysis (MCA) and supply-demand theory have led to appreciable understanding of the systems properties of metabolic networks that are subject exclusively to metabolic regulation. Supply-demand theory has not yet considered gene-expression regulation explicitly whilst a variant of MCA, i.e. Hierarchical Control Analysis (HCA), has done so. Existing analyses based on control engineering approaches have not been very explicit about whether metabolic or gene-expression regulation would be involved, but designed different ways in which regulation could be organized, with the potential of causing adaptation to be perfect. This study integrates control engineering and classical MCA augmented with supply-demand theory and HCA. Because gene-expression regulation involves time integration, it is identified as a natural instantiation of the 'integral control' (or near integral control) known in control engineering. This study then focuses on robustness against and adaptation to perturbations of process activities in the network, which could result from environmental perturbations, mutations or slow noise. It is shown however that this type of 'integral control' should rarely be expected to lead to the 'perfect adaptation': although the gene-expression regulation increases the robustness of important metabolite concentrations, it rarely makes them infinitely robust. For perfect adaptation to occur, the protein degradation reactions should be zero order in the concentration of the protein, which may be rare biologically for cells growing steadily. A proposed new framework integrating the methodologies of control engineering and metabolic and hierarchical control analysis, improves the understanding of biological systems that are regulated both metabolically and by gene expression. In particular, the new approach enables one to address the issue whether the intracellular biochemical networks that have been and are being identified by genomics and systems biology, correspond to the 'perfect' regulatory structures designed by control engineering vis-à-vis optimal functions such as robustness. To the extent that they are not, the analyses suggest how they may become so and this in turn should facilitate synthetic biology and metabolic engineering.

Construction of human induced pluripotent stem cell-derived oriented bone matrix microstructure by using in vitro engineered anisotropic culture model.

PubMed

Ozasa, Ryosuke; Matsugaki, Aira; Isobe, Yoshihiro; Saku, Taro; Yun, Hui-Suk; Nakano, Takayoshi

2018-02-01

Bone tissue has anisotropic microstructure based on collagen/biological apatite orientation, which plays essential roles in the mechanical and biological functions of bone. However, obtaining an appropriate anisotropic microstructure during the bone regeneration process remains a great challenging. A powerful strategy for the control of both differentiation and structural development of newly-formed bone is required in bone tissue engineering, in order to realize functional bone tissue regeneration. In this study, we developed a novel anisotropic culture model by combining human induced pluripotent stem cells (hiPSCs) and artificially-controlled oriented collagen scaffold. The oriented collagen scaffold allowed hiPSCs-derived osteoblast alignment and further construction of anisotropic bone matrix which mimics the bone tissue microstructure. To the best of our knowledge, this is the first report showing the construction of bone mimetic anisotropic bone matrix microstructure from hiPSCs. Moreover, we demonstrated for the first time that the hiPSCs-derived osteoblasts possess a high level of intact functionality to regulate cell alignment. © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 360-369, 2018. © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc.

Biological functioning of PAH-polluted and thermal desorption-treated soils assessed by fauna and microbial bioindicators.

PubMed

Cébron, Aurélie; Cortet, Jérôme; Criquet, Stéven; Biaz, Asmaa; Calvert, Virgile; Caupert, Cécile; Pernin, Céline; Leyval, Corinne

2011-11-01

A large number of soil bioindicators were used to assess biological diversity and activity in soil polluted with polycyclic aromatic hydrocarbons (PAHs) and the same soil after thermal desorption (TD) treatment. Abundance and biodiversity of bacteria, fungi, protozoa, nematodes and microarthropods, as well as functional parameters such as enzymatic activities and soil respiration, were assessed during a two year period of in situ monitoring. We investigated the influence of vegetation (spontaneous vegetation and Medicago sativa) and TD treatment on biological functioning. Multivariate analysis was performed to analyze the whole data set. A principal response curve (PRC) technique was used to evaluate the different treatments (various vegetation and contaminated vs. TD soil) contrasted with control (bare) soil over time. Our results indicated the value of using a number of complementary bioindicators, describing both diversity and functions, to assess the influence of vegetation on soil and discriminate polluted from thermal desorption (TD)-treated soil. Plants had an influence on the abundance and activity of all organisms examined in our study, favoring the whole trophic chain development. However, although TD-treated soil had a high abundance and diversity of microorganisms and fauna, enzymatic activities were weak because of the strong physical and chemical modifications of this soil. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Biological control via "ecological" damping: An approach that attenuates non-target effects.

PubMed

Parshad, Rana D; Quansah, Emmanuel; Black, Kelly; Beauregard, Matthew

2016-03-01

In this work we develop and analyze a mathematical model of biological control to prevent or attenuate the explosive increase of an invasive species population, that functions as a top predator, in a three-species food chain. We allow for finite time blow-up in the model as a mathematical construct to mimic the explosive increase in population, enabling the species to reach "disastrous", and uncontrollable population levels, in a finite time. We next improve the mathematical model and incorporate controls that are shown to drive down the invasive population growth and, in certain cases, eliminate blow-up. Hence, the population does not reach an uncontrollable level. The controls avoid chemical treatments and/or natural enemy introduction, thus eliminating various non-target effects associated with such classical methods. We refer to these new controls as "ecological damping", as their inclusion dampens the invasive species population growth. Further, we improve prior results on the regularity and Turing instability of the three-species model that were derived in Parshad et al. (2014). Lastly, we confirm the existence of spatiotemporal chaos. Copyright © 2016 Elsevier Inc. All rights reserved.

Tuning-free controller to accurately regulate flow rates in a microfluidic network

NASA Astrophysics Data System (ADS)

Heo, Young Jin; Kang, Junsu; Kim, Min Jun; Chung, Wan Kyun

2016-03-01

We describe a control algorithm that can improve accuracy and stability of flow regulation in a microfluidic network that uses a conventional pressure pump system. The algorithm enables simultaneous and independent control of fluid flows in multiple micro-channels of a microfluidic network, but does not require any model parameters or tuning process. We investigate robustness and optimality of the proposed control algorithm and those are verified by simulations and experiments. In addition, the control algorithm is compared with a conventional PID controller to show that the proposed control algorithm resolves critical problems induced by the PID control. The capability of the control algorithm can be used not only in high-precision flow regulation in the presence of disturbance, but in some useful functions for lab-on-a-chip devices such as regulation of volumetric flow rate, interface position control of two laminar flows, valveless flow switching, droplet generation and particle manipulation. We demonstrate those functions and also suggest further potential biological applications which can be accomplished by the proposed control framework.

Tuning-free controller to accurately regulate flow rates in a microfluidic network

PubMed Central

Heo, Young Jin; Kang, Junsu; Kim, Min Jun; Chung, Wan Kyun

2016-01-01

We describe a control algorithm that can improve accuracy and stability of flow regulation in a microfluidic network that uses a conventional pressure pump system. The algorithm enables simultaneous and independent control of fluid flows in multiple micro-channels of a microfluidic network, but does not require any model parameters or tuning process. We investigate robustness and optimality of the proposed control algorithm and those are verified by simulations and experiments. In addition, the control algorithm is compared with a conventional PID controller to show that the proposed control algorithm resolves critical problems induced by the PID control. The capability of the control algorithm can be used not only in high-precision flow regulation in the presence of disturbance, but in some useful functions for lab-on-a-chip devices such as regulation of volumetric flow rate, interface position control of two laminar flows, valveless flow switching, droplet generation and particle manipulation. We demonstrate those functions and also suggest further potential biological applications which can be accomplished by the proposed control framework. PMID:26987587

Single molecule thermodynamics in biological motors.

PubMed

Taniguchi, Yuichi; Karagiannis, Peter; Nishiyama, Masayoshi; Ishii, Yoshiharu; Yanagida, Toshio

2007-04-01

Biological molecular machines use thermal activation energy to carry out various functions. The process of thermal activation has the stochastic nature of output events that can be described according to the laws of thermodynamics. Recently developed single molecule detection techniques have allowed each distinct enzymatic event of single biological machines to be characterized providing clues to the underlying thermodynamics. In this study, the thermodynamic properties in the stepping movement of a biological molecular motor have been examined. A single molecule detection technique was used to measure the stepping movements at various loads and temperatures and a range of thermodynamic parameters associated with the production of each forward and backward step including free energy, enthalpy, entropy and characteristic distance were obtained. The results show that an asymmetry in entropy is a primary factor that controls the direction in which the motor will step. The investigation on single molecule thermodynamics has the potential to reveal dynamic properties underlying the mechanisms of how biological molecular machines work.

Imaging of the interaction of low frequency electric fields with biological tissues by optical coherence tomography

NASA Astrophysics Data System (ADS)

Peña, Adrian F.; Devine, Jack; Doronin, Alexander; Meglinski, Igor

2014-03-01

We report the use of conventional Optical Coherence Tomography (OCT) for visualization of propagation of low frequency electric field in soft biological tissues ex vivo. To increase the overall quality of the experimental images an adaptive Wiener filtering technique has been employed. Fourier domain correlation has been subsequently applied to enhance spatial resolution of images of biological tissues influenced by low frequency electric field. Image processing has been performed on Graphics Processing Units (GPUs) utilizing Compute Unified Device Architecture (CUDA) framework in the frequencydomain. The results show that variation in voltage and frequency of the applied electric field relates exponentially to the magnitude of its influence on biological tissue. The magnitude of influence is about twice more for fresh tissue samples in comparison to non-fresh ones. The obtained results suggest that OCT can be used for observation and quantitative evaluation of the electro-kinetic changes in biological tissues under different physiological conditions, functional electrical stimulation, and potentially can be used non-invasively for food quality control.

Teaching About "Brain and Learning" in High School Biology Classes: Effects on Teachers' Knowledge and Students' Theory of Intelligence.

PubMed

Dekker, Sanne; Jolles, Jelle

2015-01-01

This study evaluated a new teaching module about "Brain and Learning" using a controlled design. The module was implemented in high school biology classes and comprised three lessons: (1) brain processes underlying learning; (2) neuropsychological development during adolescence; and (3) lifestyle factors that influence learning performance. Participants were 32 biology teachers who were interested in "Brain and Learning" and 1241 students in grades 8-9. Teachers' knowledge and students' beliefs about learning potential were examined using online questionnaires. Results indicated that before intervention, biology teachers were significantly less familiar with how the brain functions and develops than with its structure and with basic neuroscientific concepts (46 vs. 75% correct answers). After intervention, teachers' knowledge of "Brain and Learning" had significantly increased (64%), and more students believed that intelligence is malleable (incremental theory). This emphasizes the potential value of a short teaching module, both for improving biology teachers' insights into "Brain and Learning," and for changing students' beliefs about intelligence.

Estimating economic thresholds for pest control: an alternative procedure.

PubMed

Ramirez, O A; Saunders, J L

1999-04-01

An alternative methodology to determine profit maximizing economic thresholds is developed and illustrated. An optimization problem based on the main biological and economic relations involved in determining a profit maximizing economic threshold is first advanced. From it, a more manageable model of 2 nonsimultaneous reduced-from equations is derived, which represents a simpler but conceptually and statistically sound alternative. The model recognizes that yields and pest control costs are a function of the economic threshold used. Higher (less strict) economic thresholds can result in lower yields and, therefore, a lower gross income from the sale of the product, but could also be less costly to maintain. The highest possible profits will be obtained by using the economic threshold that results in a maximum difference between gross income and pest control cost functions.

Differential RNA-seq analysis comparing APC-defective and APC-restored SW480 colorectal cancer cells.

PubMed

King, Lauren E; Love, Christopher G; Sieber, Oliver M; Faux, Maree C; Burgess, Antony W

2016-03-01

The adenomatous polyposis coli (APC) tumour suppressor gene is mutated in about 80% of colorectal cancers (CRC) Brannon et al. (2014) [1]. APC is a large multifunctional protein that regulates many biological functions including Wnt signalling (through the regulation of beta-catenin stability) Reya and Clevers (2005) [2], cell migration Kroboth et al. (2007), Sansom et al. (2004) [3], [4], mitosis Kaplan et al. (2001) [5], cell adhesion Faux et al. (2004), Carothers et al. (2001) [6], [7] and differentiation Sansom et al. (2004) [4]. Although the role of APC in CRC is often described as the deregulation of Wnt signalling, its other biological functions suggest that there are other factors at play that contribute to the onset of adenomas and the progression of CRC upon the truncation of APC. To identify genes and pathways that are dysregulated as a consequence of loss of function of APC, we compared the gene expression profiles of the APC mutated human CRC cell line SW480 following reintroduction of wild-type APC (SW480 + APC) or empty control vector (SW480 + vector control) Faux et al. (2004) . Here we describe the RNA-seq data derived for three biological replicates of parental SW480, SW480 + vector control and SW480 + APC cells, and present the bioinformatics pipeline used to test for differential gene expression and pathway enrichment analysis. A total of 1735 genes showed significant differential expression when APC was restored and were enriched for genes associated with cell polarity, Wnt signalling and the epithelial to mesenchymal transition. There was additional enrichment for genes involved in cell-cell adhesion, cell-matrix junctions, angiogenesis, axon morphogenesis and cell movement. The raw and analysed RNA-seq data have been deposited in the Gene Expression Omnibus (GEO) database under accession number GSE76307. This dataset is useful for further investigations of the impact of APC mutation on the properties of colorectal cancer cells.

ChpA Controls Twitching Motility and Broadly Affects Gene Expression in the Biological Control Agent Lysobacter enzymogenes.

PubMed

Zhou, Mimi; Shen, Danyu; Xu, Gaoge; Liu, Fengquan; Qian, Guoliang

2017-05-01

Lysobacter enzymogenes (L. enzymogenes) is an agriculturally important Gram-negative bacterium that employs T4P (type IV pili)-driven twitching motility to exhibit its antifungal function. Yet, it is still unclear how this bacterium regulates its twitching motility. Here, by using strain OH11 as the working model organism, we showed that a hybrid two-component system ChpA acts as a positive regulator in controlling twitching motility in L. enzymogenes. ChpA is a hybrid TCS (two-component transduction system) contains 7 domains including those for auto-phosphorylation and phosphate group transfer, as well as a phosphate receiver (REC) domain. Mutation of chpA completely abolished the wild-type twitching motility, as evidenced by the absence of mobile cells at the margin of the mutant colonies. Further studies of domain-deletion and phenotypic characterization reveal that domains responsible for phosphorylation and phosphotransfer, but not the REC domain, were indispensable for ChpA in regulating twitching motility. Transcriptome analyses of the chpA knockout strain indicated that ChpA was extensively involved in controlling expression of a wide variety of genes (totaling 243). The products of these differentially expressed genes were involved in multiple physiological and biological functions in L. enzymogenes. Thus, we have not only identified a new regulator controlling twitching motility in L. enzymogenes, but also provided the first report demonstrating the broad impact of the conserved ChpA in gene regulation in Gram-negative bacteria.

The relativity of biological function.

PubMed

Laubichler, Manfred D; Stadler, Peter F; Prohaska, Sonja J; Nowick, Katja

2015-12-01

Function is a central concept in biological theories and explanations. Yet discussions about function are often based on a narrow understanding of biological systems and processes, such as idealized molecular systems or simple evolutionary, i.e., selective, dynamics. Conflicting conceptions of function continue to be used in the scientific literature to support certain claims, for instance about the fraction of "functional DNA" in the human genome. Here we argue that all biologically meaningful interpretations of function are necessarily context dependent. This implies that they derive their meaning as well as their range of applicability only within a specific theoretical and measurement context. We use this framework to shed light on the current debate about functional DNA and argue that without considering explicitly the theoretical and measurement contexts all attempts to integrate biological theories are prone to fail.

[Asynchronous asymmetry (sexual and lateral differentiation--a consequence of asynchronous evolution)].

PubMed

Geodakian, V A

1993-01-01

In the paper is presented a unified interpretation of sex differentiation and lateral asymmetry as asynchronous evolution. The operative subsystems, i.e. the male and the left hemisphere of the brain evolutionize earlier than the conservative ones, i.e. the female and the right hemisphere. New functions appear at first in males and after many generations they are transferred to females. The leading centers of their control are at first originated in the left hemisphere, then they are translocated to the right one. The criterion for functions localization in the hemisphere is their evolutionary age: new functions are controlled by the left hemisphere, old functions by the right one. Therefore the left hemisphere is socio-cultural, ethnic, the right one is biological, special. The theory explains from a single standpoint the phenomena of sex, handedness, nervous crossover, as well as many know facts, and predicts the new ones.

Therapeutic synthetic gene networks.

PubMed

Karlsson, Maria; Weber, Wilfried

2012-10-01

The field of synthetic biology is rapidly expanding and has over the past years evolved from the development of simple gene networks to complex treatment-oriented circuits. The reprogramming of cell fate with open-loop or closed-loop synthetic control circuits along with biologically implemented logical functions have fostered applications spanning over a wide range of disciplines, including artificial insemination, personalized medicine and the treatment of cancer and metabolic disorders. In this review we describe several applications of interactive gene networks, a synthetic biology-based approach for future gene therapy, as well as the utilization of synthetic gene circuits as blueprints for the design of stimuli-responsive biohybrid materials. The recent progress in synthetic biology, including the rewiring of biosensing devices with the body's endogenous network as well as novel therapeutic approaches originating from interdisciplinary work, generates numerous opportunities for future biomedical applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

Biological Soft Robotics.

PubMed

Feinberg, Adam W

2015-01-01

In nature, nanometer-scale molecular motors are used to generate force within cells for diverse processes from transcription and transport to muscle contraction. This adaptability and scalability across wide temporal, spatial, and force regimes have spurred the development of biological soft robotic systems that seek to mimic and extend these capabilities. This review describes how molecular motors are hierarchically organized into larger-scale structures in order to provide a basic understanding of how these systems work in nature and the complexity and functionality we hope to replicate in biological soft robotics. These span the subcellular scale to macroscale, and this article focuses on the integration of biological components with synthetic materials, coupled with bioinspired robotic design. Key examples include nanoscale molecular motor-powered actuators, microscale bacteria-controlled devices, and macroscale muscle-powered robots that grasp, walk, and swim. Finally, the current challenges and future opportunities in the field are addressed.

The biology of cultural conflict

PubMed Central

Berns, Gregory S.; Atran, Scott

2012-01-01

Although culture is usually thought of as the collection of knowledge and traditions that are transmitted outside of biology, evidence continues to accumulate showing how biology and culture are inseparably intertwined. Cultural conflict will occur only when the beliefs and traditions of one cultural group represent a challenge to individuals of another. Such a challenge will elicit brain processes involved in cognitive decision-making, emotional activation and physiological arousal associated with the outbreak, conduct and resolution of conflict. Key targets to understand bio-cultural differences include primitive drives—how the brain responds to likes and dislikes, how it discounts the future, and how this relates to reproductive behaviour—but also higher level functions, such as how the mind represents and values the surrounding physical and social environment. Future cultural wars, while they may bear familiar labels of religion and politics, will ultimately be fought over control of our biology and our environment. PMID:22271779

The biology of cultural conflict.

PubMed

Berns, Gregory S; Atran, Scott

2012-03-05

Although culture is usually thought of as the collection of knowledge and traditions that are transmitted outside of biology, evidence continues to accumulate showing how biology and culture are inseparably intertwined. Cultural conflict will occur only when the beliefs and traditions of one cultural group represent a challenge to individuals of another. Such a challenge will elicit brain processes involved in cognitive decision-making, emotional activation and physiological arousal associated with the outbreak, conduct and resolution of conflict. Key targets to understand bio-cultural differences include primitive drives-how the brain responds to likes and dislikes, how it discounts the future, and how this relates to reproductive behaviour-but also higher level functions, such as how the mind represents and values the surrounding physical and social environment. Future cultural wars, while they may bear familiar labels of religion and politics, will ultimately be fought over control of our biology and our environment.

A biomimetic colorimetric logic gate system based on multi-functional peptide-mediated gold nanoparticle assembly.

PubMed

Li, Yong; Li, Wang; He, Kai-Yu; Li, Pei; Huang, Yan; Nie, Zhou; Yao, Shou-Zhuo

2016-04-28

In natural biological systems, proteins exploit various functional peptide motifs to exert target response and activity switch, providing a functional and logic basis for complex cellular activities. Building biomimetic peptide-based bio-logic systems is highly intriguing but remains relatively unexplored due to limited logic recognition elements and complex signal outputs. In this proof-of-principle work, we attempted to address these problems by utilizing multi-functional peptide probes and the peptide-mediated nanoparticle assembly system. Here, the rationally designed peptide probes function as the dual-target responsive element specifically responsive to metal ions and enzymes as well as the mediator regulating the assembly of gold nanoparticles (AuNPs). Taking advantage of Zn2+ ions and chymotrypsin as the model inputs of metal ions and enzymes, respectively, we constructed the peptide logic system computed by the multi-functional peptide probes and outputted by the readable colour change of AuNPs. In this way, the representative binary basic logic gates (AND, OR, INHIBIT, NAND, IMPLICATION) have been achieved by delicately coding the peptide sequence, demonstrating the versatility of our logic system. Additionally, we demonstrated that the three-input combinational logic gate (INHIBIT-OR) could also be successfully integrated and applied as a multi-tasking biosensor for colorimetric detection of dual targets. This nanoparticle-based peptide logic system presents a valid strategy to illustrate peptide information processing and provides a practical platform for executing peptide computing or peptide-related multiplexing sensing, implying that the controllable nanomaterial assembly is a promising and potent methodology for the advancement of biomimetic bio-logic computation.

Why magnetic and electromagnetic effects in biology are irreproducible and contradictory?

PubMed

Buchachenko, Anatoly

2016-01-01

The main source of magnetic and electromagnetic effects in biological systems is now generally accepted and demonstrated in this paper to be radical pair mechanism which implies pairwise generation of radicals in biochemical reactions. This mechanism was convincingly established for enzymatic adenosine triphosphate (ATP) and desoxynucleic acid (DNA) synthesis by using catalyzing metal ions with magnetic nuclei ((25)Mg, (43)Ca, (67)Zn) and supported by magnetic field effects on these reactions. The mechanism, is shown to function in medicine as a medical remedy or technology (trans-cranial magnetic stimulation, nuclear magnetic control of the ATP synthesis in heart muscle, the killing of cancer cells by suppression of DNA synthesis). However, the majority of magnetic effects in biology remain to be irreproducible, contradictory, and enigmatic. Three sources of such a state are shown in this paper to be: the presence of paramagnetic metal ions as a component of enzymatic site or as an impurity in an uncontrollable amount; the property of the radical pair mechanism to function at a rather high concentration of catalyzing metal ions, when at least two ions enter into the catalytic site; and the kinetic restrictions, which imply compatibility of chemical and spin dynamics in radical pair. It is important to keep in mind these factors to properly understand and predict magnetic effects in magneto-biology and biology itself and deliberately use them in medicine. © 2015 Wiley Periodicals, Inc.

Manipulating lipid membrane architecture by liquid crystal-analog curvature elasticity (Presentation Recording)

NASA Astrophysics Data System (ADS)

Lee, Sin-Doo

2015-10-01

Soft matters such as liquid crystals and biological molecules exhibit a variety of interesting physical phenomena as well as new applications. Recently, in mimicking biological systems that have the ability to sense, regulate, grow, react, and regenerate in a highly responsive and self-adaptive manner, the significance of the liquid crystal order in living organisms, for example, a biological membrane possessing the lamellar order, is widely recognized from the viewpoints of physics and chemistry of interfaces and membrane biophysics. Lipid bilayers, resembling cell membranes, provide primary functions for the transport of biological components of ions and molecules in various cellular activities, including vesicle budding and membrane fusion, through lateral organization of the membrane components such as proteins. In this lecture, I will describe how the liquid crystal-analog curvature elasticity of a lipid bilayer plays a critical role in developing a new platform for understanding diverse biological functions at a cellular level. The key concept is to manipulate the local curvature at an interface between a solid substrate and a model membrane. Two representative examples will be demonstrated: one of them is the topographic control of lipid rafts in a combinatorial array where the ligand-receptor binding event occurs and the other concerns the reconstitution of a ring-type lipid raft in bud-mimicking architecture within the framework of the curvature elasticity.

Antimicrobial Peptides and Wound Healing: Biological and Therapeutic Considerations

PubMed Central

Mangoni, Maria Luisa; McDermott, Alison M.; Zasloff, Michael

2016-01-01

Repair of tissue wounds is a fundamental process to re-establish tissue integrity and regular function. Importantly, infection is a major factor that hinders wound healing. Multicellular organisms have evolved an arsenal of host-defence molecules, including antimicrobial peptides (AMPs), aimed at controlling microbial proliferation and at modulating the host's immune response to a variety of biological or physical insults. In this brief review we provide the evidence for a role of AMPs as endogenous mediators of wound healing and their promising therapeutic potential for treatment of non-life threatening skin and other epithelial injuries. PMID:26738772

tRNA biology charges to the front

PubMed Central

Phizicky, Eric M.; Hopper, Anita K.

2010-01-01

tRNA biology has come of age, revealing an unprecedented level of understanding and many unexpected discoveries along the way. This review highlights new findings on the diverse pathways of tRNA maturation, and on the formation and function of a number of modifications. Topics of special focus include the regulation of tRNA biosynthesis, quality control tRNA turnover mechanisms, widespread tRNA cleavage pathways activated in response to stress and other growth conditions, emerging evidence of signaling pathways involving tRNA and cleavage fragments, and the sophisticated intracellular tRNA trafficking that occurs during and after biosynthesis. PMID:20810645

Regulatory RNA in Mycobacterium tuberculosis, back to basics.

PubMed

Schwenk, Stefan; Arnvig, Kristine B

2018-06-01

Since the turn of the millenium, RNA-based control of gene expression has added an extra dimension to the central dogma of molecular biology. Still, the roles of Mycobacterium tuberculosis regulatory RNAs and the proteins that facilitate their functions remain elusive, although there can be no doubt that RNA biology plays a central role in the baterium's adaptation to its many host environments. In this review, we have presented examples from model organisms and from M. tuberculosis to showcase the abundance and versatility of regulatory RNA, in order to emphasise the importance of these 'fine-tuners' of gene expression.

Multiphoton microscopy for the in-situ investigation of cellular processes and integrity in cryopreservation.

PubMed

Doerr, Daniel; Stark, Martin; Ehrhart, Friederike; Zimmermann, Heiko; Stracke, Frank

2009-08-01

In this study we demonstrate a new noninvasive imaging method to monitor freezing processes in biological samples and to investigate life in the frozen state. It combines a laser scanning microscope with a computer-controlled cryostage. Nearinfrared (NIR) femtosecond laser pulses evoke the fluorescence of endogenous fluorophores and fluorescent labels due to multiphoton absorption.The inherent optical nonlinearity of multiphoton absorption allows 3D fluorescence imaging for optical tomography of frozen biological material in-situ. As an example for functional imaging we use fluorescence lifetime imaging (FLIM) to create images with chemical and physical contrast.

Ponderomotive phase plate for transmission electron microscopes

DOEpatents

Reed, Bryan W [Livermore, CA

2012-07-10

A ponderomotive phase plate system and method for controllably producing highly tunable phase contrast transfer functions in a transmission electron microscope (TEM) for high resolution and biological phase contrast imaging. The system and method includes a laser source and a beam transport system to produce a focused laser crossover as a phase plate, so that a ponderomotive potential of the focused laser crossover produces a scattering-angle-dependent phase shift in the electrons of the post-sample electron beam corresponding to a desired phase contrast transfer function.

The Redox Proteome*

PubMed Central

Go, Young-Mi; Jones, Dean P.

2013-01-01

The redox proteome consists of reversible and irreversible covalent modifications that link redox metabolism to biologic structure and function. These modifications, especially of Cys, function at the molecular level in protein folding and maturation, catalytic activity, signaling, and macromolecular interactions and at the macroscopic level in control of secretion and cell shape. Interaction of the redox proteome with redox-active chemicals is central to macromolecular structure, regulation, and signaling during the life cycle and has a central role in the tolerance and adaptability to diet and environmental challenges. PMID:23861437

Functionalization of 3D scaffolds with protein-releasing biomaterials for intracellular delivery.

PubMed

Seras-Franzoso, Joaquin; Steurer, Christoph; Roldán, Mònica; Vendrell, Meritxell; Vidaurre-Agut, Carla; Tarruella, Anna; Saldaña, Laura; Vilaboa, Nuria; Parera, Marc; Elizondo, Elisa; Ratera, Imma; Ventosa, Nora; Veciana, Jaume; Campillo-Fernández, Alberto J; García-Fruitós, Elena; Vázquez, Esther; Villaverde, Antonio

2013-10-10

Appropriate combinations of mechanical and biological stimuli are required to promote proper colonization of substrate materials in regenerative medicine. In this context, 3D scaffolds formed by compatible and biodegradable materials are under continuous development in an attempt to mimic the extracellular environment of mammalian cells. We have here explored how novel 3D porous scaffolds constructed by polylactic acid, polycaprolactone or chitosan can be decorated with bacterial inclusion bodies, submicron protein particles formed by releasable functional proteins. A simple dipping-based decoration method tested here specifically favors the penetration of the functional particles deeper than 300μm from the materials' surface. The functionalized surfaces support the intracellular delivery of biologically active proteins to up to more than 80% of the colonizing cells, a process that is slightly influenced by the chemical nature of the scaffold. The combination of 3D soft scaffolds and protein-based sustained release systems (Bioscaffolds) offers promise in the fabrication of bio-inspired hybrid matrices for multifactorial control of cell proliferation in tissue engineering under complex architectonic setting-ups. © 2013.

The GS (genetic selection) Principle.

PubMed

Abel, David L

2009-01-01

The GS (Genetic Selection) Principle states that biological selection must occur at the nucleotide-sequencing molecular-genetic level of 3'5' phosphodiester bond formation. After-the-fact differential survival and reproduction of already-living phenotypic organisms (ordinary natural selection) does not explain polynucleotide prescription and coding. All life depends upon literal genetic algorithms. Even epigenetic and "genomic" factors such as regulation by DNA methylation, histone proteins and microRNAs are ultimately instructed by prior linear digital programming. Biological control requires selection of particular configurable switch-settings to achieve potential function. This occurs largely at the level of nucleotide selection, prior to the realization of any integrated biofunction. Each selection of a nucleotide corresponds to the setting of two formal binary logic gates. The setting of these switches only later determines folding and binding function through minimum-free-energy sinks. These sinks are determined by the primary structure of both the protein itself and the independently prescribed sequencing of chaperones. The GS Principle distinguishes selection of existing function (natural selection) from selection for potential function (formal selection at decision nodes, logic gates and configurable switch-settings).

Capturing cooperative interactions with the PSI-MI format

PubMed Central

Van Roey, Kim; Orchard, Sandra; Kerrien, Samuel; Dumousseau, Marine; Ricard-Blum, Sylvie; Hermjakob, Henning; Gibson, Toby J.

2013-01-01

The complex biological processes that control cellular function are mediated by intricate networks of molecular interactions. Accumulating evidence indicates that these interactions are often interdependent, thus acting cooperatively. Cooperative interactions are prevalent in and indispensible for reliable and robust control of cell regulation, as they underlie the conditional decision-making capability of large regulatory complexes. Despite an increased focus on experimental elucidation of the molecular details of cooperative binding events, as evidenced by their growing occurrence in literature, they are currently lacking from the main bioinformatics resources. One of the contributing factors to this deficiency is the lack of a computer-readable standard representation and exchange format for cooperative interaction data. To tackle this shortcoming, we added functionality to the widely used PSI-MI interchange format for molecular interaction data by defining new controlled vocabulary terms that allow annotation of different aspects of cooperativity without making structural changes to the underlying XML schema. As a result, we are able to capture cooperative interaction data in a structured format that is backward compatible with PSI-MI–based data and applications. This will facilitate the storage, exchange and analysis of cooperative interaction data, which in turn will advance experimental research on this fundamental principle in biology. Database URL: http://psi-mi-cooperativeinteractions.embl.de/ PMID:24067240

Strategies for new and improved vaccines against ticks and tick-borne diseases.

PubMed

de la Fuente, J; Kopáček, P; Lew-Tabor, A; Maritz-Olivier, C

2016-12-01

Ticks infest a variety of animal species and transmit pathogens causing disease in both humans and animals worldwide. Tick-host-pathogen interactions have evolved through dynamic processes that accommodated the genetic traits of the hosts, pathogens transmitted and the vector tick species that mediate their development and survival. New approaches for tick control are dependent on defining molecular interactions between hosts, ticks and pathogens to allow for discovery of key molecules that could be tested in vaccines or new generation therapeutics for intervention of tick-pathogen cycles. Currently, tick vaccines constitute an effective and environmentally sound approach for the control of ticks and the transmission of the associated tick-borne diseases. New candidate protective antigens will most likely be identified by focusing on proteins with relevant biological function in the feeding, reproduction, development, immune response, subversion of host immunity of the tick vector and/or molecules vital for pathogen infection and transmission. This review addresses different approaches and strategies used for the discovery of protective antigens, including focusing on relevant tick biological functions and proteins, reverse genetics, vaccinomics and tick protein evolution and interactomics. New and improved tick vaccines will most likely contain multiple antigens to control tick infestations and pathogen infection and transmission. © 2016 John Wiley & Sons Ltd.

ON THE BIOMECHANICAL FUNCTION OF SCAFFOLDS FOR ENGINEERING LOAD BEARING SOFT TISSUES

PubMed Central

Stella, John A.; D’Amore, Antonio; Wagner, William R.; Sacks, Michael S.

2010-01-01

Replacement or regeneration of load bearing soft tissues has long been the impetus for the development bioactive materials. While maturing, current efforts continue to be confounded by our lack of understanding of the intricate multi-scale hierarchical arrangements and interactions typically found in native tissues. The current state of the art in biomaterial processing enables a degree of controllable microstructure that can be used for the development of model systems to deduce fundamental biological implications of matrix morphologies on cell function. Furthermore, the development of computational frameworks which allow for the simulation of experimentally derived observations represents a positive departure from what has mostly been an empirically driven field, enabling a deeper understanding of the highly complex biological mechanisms we wish to ultimately emulate. Ongoing research is actively pursuing new materials and processing methods to control material structure down to the micro-scale to sustain or improve cell viability, guide tissue growth, and provide mechanical integrity all while exhibiting the capacity to degrade in a controlled manner. The purpose of this review is not to focus solely on material processing but to assess the ability of these techniques to produce mechanically sound tissue surrogates, highlight the unique structural characteristics produced in these materials, and discuss how this translates to distinct macroscopic biomechanical behaviors. PMID:20060509

Engineering challenges for instrumenting and controlling integrated organ-on-chip systems.

PubMed

Wikswo, John P; Block, Frank E; Cliffel, David E; Goodwin, Cody R; Marasco, Christina C; Markov, Dmitry A; McLean, David L; McLean, John A; McKenzie, Jennifer R; Reiserer, Ronald S; Samson, Philip C; Schaffer, David K; Seale, Kevin T; Sherrod, Stacy D

2013-03-01

The sophistication and success of recently reported microfabricated organs-on-chips and human organ constructs have made it possible to design scaled and interconnected organ systems that may significantly augment the current drug development pipeline and lead to advances in systems biology. Physiologically realistic live microHuman (μHu) and milliHuman (mHu) systems operating for weeks to months present exciting and important engineering challenges such as determining the appropriate size for each organ to ensure appropriate relative organ functional activity, achieving appropriate cell density, providing the requisite universal perfusion media, sensing the breadth of physiological responses, and maintaining stable control of the entire system, while maintaining fluid scaling that consists of ~5 mL for the mHu and ~5 μL for the μHu. We believe that successful mHu and μHu systems for drug development and systems biology will require low-volume microdevices that support chemical signaling, microfabricated pumps, valves and microformulators, automated optical microscopy, electrochemical sensors for rapid metabolic assessment, ion mobility-mass spectrometry for real-time molecular analysis, advanced bioinformatics, and machine learning algorithms for automated model inference and integrated electronic control. Toward this goal, we are building functional prototype components and are working toward top-down system integration.

Developing PFC representations using reinforcement learning

PubMed Central

Reynolds, Jeremy R.; O'Reilly, Randall C.

2009-01-01

From both functional and biological considerations, it is widely believed that action production, planning, and goal-oriented behaviors supported by the frontal cortex are organized hierarchically (Fuster, 1990, Koechlin, Ody, & Kouneiher, 2003, & Miller, Galanter, & Pribram, 1960) However, the nature of the different levels of the hierarchy remains unclear, and little attention has been paid to the origins of such a hierarchy. We address these issues through biologically-inspired computational models that develop representations through reinforcement learning. We explore several different factors in these models that might plausibly give rise to a hierarchical organization of representations within the PFC, including an initial connectivity hierarchy within PFC, a hierarchical set of connections between PFC and subcortical structures controlling it, and differential synaptic plasticity schedules. Simulation results indicate that architectural constraints contribute to the segregation of different types of representations, and that this segregation facilitates learning. These findings are consistent with the idea that there is a functional hierarchy in PFC, as captured in our earlier computational models of PFC function and a growing body of empirical data. PMID:19591977

Tinbergen on mirror neurons.

PubMed

Heyes, Cecilia

2014-01-01

Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology-the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible 'best explanation' for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of 'survival value', should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding-or another social cognitive function-by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories.

Designer amphiphilic proteins as building blocks for the intracellular formation of organelle-like compartments

NASA Astrophysics Data System (ADS)

Huber, Matthias C.; Schreiber, Andreas; von Olshausen, Philipp; Varga, Balázs R.; Kretz, Oliver; Joch, Barbara; Barnert, Sabine; Schubert, Rolf; Eimer, Stefan; Kele, Péter; Schiller, Stefan M.

2015-01-01

Nanoscale biological materials formed by the assembly of defined block-domain proteins control the formation of cellular compartments such as organelles. Here, we introduce an approach to intentionally ‘program’ the de novo synthesis and self-assembly of genetically encoded amphiphilic proteins to form cellular compartments, or organelles, in Escherichia coli. These proteins serve as building blocks for the formation of artificial compartments in vivo in a similar way to lipid-based organelles. We investigated the formation of these organelles using epifluorescence microscopy, total internal reflection fluorescence microscopy and transmission electron microscopy. The in vivo modification of these protein-based de novo organelles, by means of site-specific incorporation of unnatural amino acids, allows the introduction of artificial chemical functionalities. Co-localization of membrane proteins results in the formation of functionalized artificial organelles combining artificial and natural cellular function. Adding these protein structures to the cellular machinery may have consequences in nanobiotechnology, synthetic biology and materials science, including the constitution of artificial cells and bio-based metamaterials.

Pigment composition and concentrations within the plant (Ceratophyllum demersum L.) component of the STS-89 C.E.B.A.S. Mini-Module spaceflight experiment

NASA Technical Reports Server (NTRS)

Voeste, D.; Levine, L. H.; Levine, H. G.; Blum, V.; Wheeler, R. M. (Principal Investigator)

2003-01-01

The Closed Equilibrated Biological Aquatic System (C.E.B.A.S.) Mini-Module, a Space Shuttle middeck locker payload which supports a variety of aquatic inhabitants (fish, snails, plants and bacteria) in an enclosed 8.6 L chamber, was tested for its biological stability in microgravity. The aquatic plant, Ceratophyllum demersum L., was critical for the vitality and functioning of this artificial mini-ecosystem. Its photosynthetic pigment concentrations were of interest due to their light harvesting and protective functions. "Post-flight" chlorophyll and carotenoid concentrations within Ceratophyllum apical segments were directly related to the quantities of light received in the experiments, with microgravity exposure (STS-89) failing to account for any significant deviation from ground control studies. Published by Elsevier Science Ltd on behalf of COSPAR.

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.

Emerging role of the Jun N-terminal kinase interactome in human health.

PubMed

Guo, Xiao-Xi; An, Su; Yang, Yang; Liu, Ying; Hao, Qian; Tang, Tao; Xu, Tian-Rui

2018-02-08

The c-Jun N-terminal kinases (JNKs) are located downstream of Ras-mitogen activated protein kinase signaling cascades. More than 20 years of study has shown that JNKs control cell fate and many cellular functions. JNKs and their interacting proteins form a complicated network with diverse biological functions and physiological effects. Members of the JNK interactome include Jun, amyloid precursor protein, and insulin receptor substrate. Recent studies have shown that the JNK interactome is involved in tumorigenesis, neuron development, and insulin resistance. In this review, we summarize the features of the JNK interactome and classify its members into three groups: upstream regulators, downstream effectors, and scaffold partners. We also highlight the unique cellular signaling mechanisms of JNKs and provide more insights into the roles of the JNK interactome in human diseases. © 2018 International Federation for Cell Biology.

Stiffness control of a nylon twisted coiled actuator for use in mechatronic rehabilitation devices.

PubMed

Edmonds, Brandon P R; Trejos, Ana Luisa

2017-07-01

Mechatronic rehabilitation devices, especially wearables, have been researched extensively and proven to be promising additions to physical therapy, but most designs utilize traditional actuators providing unnatural, robot-like movements. Therefore, many researchers have focused on the development of actuators that mimic biological properties to provide patients with improved results, safety, and comfort. Recently, a twisted-coiled actuator (TCA) made from nylon thread has been found to possess many of these important properties when heated, such as variable stiffness, flexibility, and high power density. So far, TCAs have been characterized in controlled environments to define their fundamental properties under simple loading configurations. However, for an actuator like this to be implemented in a biomimetic design such as an exoskeleton, it needs to be characterized and controlled as a biological muscle. One major control law that natural muscles exhibit is stiffness control, allowing humans to passively avoid injury from external forces, or move the limbs in a controlled or high impact motion. This type of control is created by the antagonistic muscle arrangement. In this paper, an antagonistic apparatus was developed to model the TCAs from a biological standpoint, the stiffness was characterized with respect to the TCA temperature, and a fully functional stiffness and position controller was implemented with an incorporated TCA thermal model. The stiffness was found to have a linear relationship to the TCA temperatures (R 2 =0.95). The controller performed with a stiffness accuracy of 98.95% and a position accuracy of 92.7%. A final trial with varying continuous position input and varying stepped stiffness input exhibited position control with R 2 =0.9638.

Multiple functionalization of fluorescent nanoparticles for specific biolabeling and drug delivery of dopamine

NASA Astrophysics Data System (ADS)

Malvindi, Maria Ada; di Corato, Riccardo; Curcio, Annalisa; Melisi, Daniela; Rimoli, Maria Grazia; Tortiglione, Claudia; Tino, Angela; George, Chandramohan; Brunetti, Virgilio; Cingolani, Roberto; Pellegrino, Teresa; Ragusa, Andrea

2011-12-01

The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release.The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release. Electronic supplementary information (ESI) available: TEM images, absorption and emission spectra, ζ-potential and DLS graphics, gel electrophoresis images, cyclic voltammograms, western blot and RT-PCR data. See DOI: 10.1039/c1nr10797f

Neuroendocrine tests of monoamine function in man: a review of basic theory and its application to the study of depressive illness.

PubMed

Checkley, S A

1980-02-01

Neuroendocrine tests are now available for studying monoamine function in the brains of patients with mental illness. Great care is required in the selection of drugs which act upon specific monoamine receptors to produce specific hormonal responses. Equal care is required in the control of biological variables which may influence hormonal release. Recently reported neuroendocrine studies of depressive illness are assessed in these terms. The results of these studies support the hypothesis that there is defective noradrenergic function in the brains of some patients with depressive illness.

Economic value of biological control in integrated pest management of managed plant systems.

PubMed

Naranjo, Steven E; Ellsworth, Peter C; Frisvold, George B

2015-01-07

Biological control is an underlying pillar of integrated pest management, yet little focus has been placed on assigning economic value to this key ecosystem service. Setting biological control on a firm economic foundation would help to broaden its utility and adoption for sustainable crop protection. Here we discuss approaches and methods available for valuation of biological control of arthropod pests by arthropod natural enemies and summarize economic evaluations in classical, augmentative, and conservation biological control. Emphasis is placed on valuation of conservation biological control, which has received little attention. We identify some of the challenges of and opportunities for applying economics to biological control to advance integrated pest management. Interaction among diverse scientists and stakeholders will be required to measure the direct and indirect costs and benefits of biological control that will allow farmers and others to internalize the benefits that incentivize and accelerate adoption for private and public good.

Regional grey matter structure differences between transsexuals and healthy controls--a voxel based morphometry study.

PubMed

Simon, Lajos; Kozák, Lajos R; Simon, Viktória; Czobor, Pál; Unoka, Zsolt; Szabó, Ádám; Csukly, Gábor

2013-01-01

Gender identity disorder (GID) refers to transsexual individuals who feel that their assigned biological gender is incongruent with their gender identity and this cannot be explained by any physical intersex condition. There is growing scientific interest in the last decades in studying the neuroanatomy and brain functions of transsexual individuals to better understand both the neuroanatomical features of transsexualism and the background of gender identity. So far, results are inconclusive but in general, transsexualism has been associated with a distinct neuroanatomical pattern. Studies mainly focused on male to female (MTF) transsexuals and there is scarcity of data acquired on female to male (FTM) transsexuals. Thus, our aim was to analyze structural MRI data with voxel based morphometry (VBM) obtained from both FTM and MTF transsexuals (n = 17) and compare them to the data of 18 age matched healthy control subjects (both males and females). We found differences in the regional grey matter (GM) structure of transsexual compared with control subjects, independent from their biological gender, in the cerebellum, the left angular gyrus and in the left inferior parietal lobule. Additionally, our findings showed that in several brain areas, regarding their GM volume, transsexual subjects did not differ significantly from controls sharing their gender identity but were different from those sharing their biological gender (areas in the left and right precentral gyri, the left postcentral gyrus, the left posterior cingulate, precuneus and calcarinus, the right cuneus, the right fusiform, lingual, middle and inferior occipital, and inferior temporal gyri). These results support the notion that structural brain differences exist between transsexual and healthy control subjects and that majority of these structural differences are dependent on the biological gender.

Packaging biological cargoes in mesoporous materials: opportunities for drug delivery.

PubMed

Siefker, Justin; Karande, Pankaj; Coppens, Marc-Olivier

2014-11-01

Confinement of biomolecules in structured nanoporous materials offers several desirable features ranging from chemical and thermal stability, to resistance to degradation from the external environment. A new generation of mesoporous materials presents exciting new possibilities for the formulation and controlled release of biological agents. Such materials address niche applications in enteral and parenteral delivery of biologics, such as peptides, polypeptides, enzymes and proteins for use as therapeutics, imaging agents, biosensors, and adjuvants. Mesoporous silica Santa Barbara Amorphous-15 (SBA-15), with its unique, tunable pore diameter, and easily functionalized surface, provides a representative example of this new generation of materials. Here, we review recent advances in the design and synthesis of nanostructured mesoporous materials, focusing on SBA-15, and highlight opportunities for the delivery of biological agents to various organ and tissue compartments. The SBA-15 platform provides a delivery carrier that is inherently separated from the active biologic due to distinct intra and extra-particle environments. This permits the SBA-15 platform to not require direct modification of the active biological therapeutic. Additionally, this makes the platform universal and allows for its application independent of the desired methods of discovery and development. The SBA-15 platform also directly addresses issues of targeted delivery and controlled release, although future challenges in the implementation of this platform reside in particle design, biocompatibility, and the tunability of the internal and external material properties. Examples illustrating the flexibility in the application of the SBA-15 platform are also discussed.

Pig Brain Mitochondria as a Biological Model for Study of Mitochondrial Respiration.

PubMed

Fišar, Z; Hroudová, J

2016-01-01

Oxidative phosphorylation is a key process of intracellular energy transfer by which mitochondria produce ATP. Isolated mitochondria serve as a biological model for understanding the mitochondrial respiration control, effects of various biologically active substances, and pathophysiology of mitochondrial diseases. The aim of our study was to evaluate pig brain mitochondria as a proper biological model for investigation of activity of the mitochondrial electron transport chain. Oxygen consumption rates of isolated pig brain mitochondria were measured using high-resolution respirometry. Mitochondrial respiration of crude mitochondrial fraction, mitochondria purified in sucrose gradient, and mitochondria purified in Percoll gradient were assayed as a function of storage time. Oxygen flux and various mitochondrial respiratory control ratios were not changed within two days of mitochondria storage on ice. Leak respiration was found higher and Complex I-linked respiration lower in purified mitochondria compared to the crude mitochondrial fraction. Damage to both outer and inner mitochondrial membrane caused by the isolation procedure was the greatest after purification in a sucrose gradient. We confirmed that pig brain mitochondria can serve as a biological model for investigation of mitochondrial respiration. The advantage of this biological model is the stability of respiratory parameters for more than 48 h and the possibility to isolate large amounts of mitochondria from specific brain areas without the need to kill laboratory animals. We suggest the use of high-resolution respirometry of pig brain mitochondria for research of the neuroprotective effects and/or mitochondrial toxicity of new medical drugs.

Provision Of Carbon Nanotube Bucky Paper Cages For Immune Shielding Of Cells, Tissues, and Medical Devices

NASA Technical Reports Server (NTRS)

Loftus, David J. (Inventor)

2006-01-01

System and method for enclosing cells and/or tissue, for purposes of growth, cell differentiation, suppression of cell differentiation, biological processing and/or transplantation of cells and tissues (biological inserts), and for secretion, sensing and monitoring of selected chemical substances and activation of gene expression of biological inserts implanted into a human body. Selected cells and/or tissue are enveloped in a "cage" that is primarily carbon nanotube Bucky paper, with a selected thickness and porosity. Optionally, selected functional groups, proteins and/or peptides are attached to the carbon nanotube cage, or included within the cage, to enhance the growth and/or differentiation of the cells and/or tissue, to select for certain cellular sub-populations, to optimize certain functions of the cells and/or tissue and/or to optimize the passage of chemicals across the cage surface(s). A cage system is also used as an immuns shield and to control operation of a nano-device or macroscopic device, located within the cage, to provide or transform a selected chemical and/or a selected signal.

Genetically Encoded Photoactuators and Photosensors for Characterization and Manipulation of Pluripotent Stem Cells

PubMed Central

Pomeroy, Jordan E.; Nguyen, Hung X.; Hoffman, Brenton D.; Bursac, Nenad

2017-01-01

Our knowledge of pluripotent stem cell biology has advanced considerably in the past four decades, but it has yet to deliver on the great promise of regenerative medicine. The slow progress can be mainly attributed to our incomplete understanding of the complex biologic processes regulating the dynamic developmental pathways from pluripotency to fully-differentiated states of functional somatic cells. Much of the difficulty arises from our lack of specific tools to query, or manipulate, the molecular scale circuitry on both single-cell and organismal levels. Fortunately, the last two decades of progress in the field of optogenetics have produced a variety of genetically encoded, light-mediated tools that enable visualization and control of the spatiotemporal regulation of cellular function. The merging of optogenetics and pluripotent stem cell biology could thus be an important step toward realization of the clinical potential of pluripotent stem cells. In this review, we have surveyed available genetically encoded photoactuators and photosensors, a rapidly expanding toolbox, with particular attention to those with utility for studying pluripotent stem cells. PMID:28912894

Toward a unified theory of childhood trauma and psychosis: A comprehensive review of epidemiological, clinical, neuropsychological and biological findings.

PubMed

Misiak, Błażej; Krefft, Maja; Bielawski, Tomasz; Moustafa, Ahmed A; Sąsiadek, Maria M; Frydecka, Dorota

2017-04-01

There is a growing body of research focused on the relationship between childhood trauma and the risk of developing psychosis. Numerous studies, including many large-scale population-based studies, controlling for possible mediating variables, provide persuasive evidence of a dose-response association and are indicative of a causal relationship. Existing evidence supports the specificity model, showing differential associations between particular adversities and clinical symptoms, with cumulative adversity causing less favorable clinical and functional outcomes in psychotic patients. To date, several psychological and biological models have been proposed to search for underlying developmental trajectories leading to the onset of psychosis, influencing psychopathological manifestation and negative functional outcomes due to a history of childhood trauma. In this article, we provide a unified review on the relationship between childhood trauma and psychosis by integrating results of epidemiological, clinical, neuropsychological and biological studies. The question whether psychosis with a positive history of childhood trauma should be considered as a new psychotic phenotype, requiring specific therapeutic interventions, warrants further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Period doubling induced by thermal noise amplification in genetic circuits

PubMed Central

Ruocco, G.; Fratalocchi, A.

2014-01-01

Rhythms of life are dictated by oscillations, which take place in a wide rage of biological scales. In bacteria, for example, oscillations have been proven to control many fundamental processes, ranging from gene expression to cell divisions. In genetic circuits, oscillations originate from elemental block such as autorepressors and toggle switches, which produce robust and noise-free cycles with well defined frequency. In some circumstances, the oscillation period of biological functions may double, thus generating bistable behaviors whose ultimate origin is at the basis of intense investigations. Motivated by brain studies, we here study an “elemental” genetic circuit, where a simple nonlinear process interacts with a noisy environment. In the proposed system, nonlinearity naturally arises from the mechanism of cooperative stability, which regulates the concentration of a protein produced during a transcription process. In this elemental model, bistability results from the coherent amplification of environmental fluctuations due to a stochastic resonance of nonlinear origin. This suggests that the period doubling observed in many biological functions might result from the intrinsic interplay between nonlinearity and thermal noise. PMID:25404210

Chromatin Computation

PubMed Central

Bryant, Barbara

2012-01-01

In living cells, DNA is packaged along with protein and RNA into chromatin. Chemical modifications to nucleotides and histone proteins are added, removed and recognized by multi-functional molecular complexes. Here I define a new computational model, in which chromatin modifications are information units that can be written onto a one-dimensional string of nucleosomes, analogous to the symbols written onto cells of a Turing machine tape, and chromatin-modifying complexes are modeled as read-write rules that operate on a finite set of adjacent nucleosomes. I illustrate the use of this “chromatin computer” to solve an instance of the Hamiltonian path problem. I prove that chromatin computers are computationally universal – and therefore more powerful than the logic circuits often used to model transcription factor control of gene expression. Features of biological chromatin provide a rich instruction set for efficient computation of nontrivial algorithms in biological time scales. Modeling chromatin as a computer shifts how we think about chromatin function, suggests new approaches to medical intervention, and lays the groundwork for the engineering of a new class of biological computing machines. PMID:22567109

[Cycloferon biological activity characteristics].

PubMed

Utkina, T M; Potekhina, L P; Kartashova, O L; Vasilchenko, A S

2014-01-01

Study the effect of cycloferon in experimental and clinical conditions on persistence properties of aurococci as well as features of their morpho-functional reaction by atomic force microscopy. The study was carried out in 12 Staphylococcus aureus clones isolated from mucous membrane of nose anterior part of a resident carrier. The effect of cycloferon in vivo was evaluated in 26 resident staphylococci carriers under the control of anti-carnosine activity of staphylococci. Anti-carnosine activity was determined by O.V. Bukharin et al. (1999), biofilm formation -by G.A. O'Toole et al. (2000). Staphylococci treated with cycloferon were studied by atomic force microscopy in contact mode using scanning probe SMM-2000 microscope. The decrease of persistence properties of staphylococci under the effect of cycloferon in vitro and in vivo may be examined as one of the mechanisms of biological activity of the preparation. A significant increase of S. aureus surface roughness and changes in their morphology under the effect of cycloferon allow stating the disorder of barrier functions in the aurococci cell wall. The data obtained expand the understanding of cycloferon biological activity mechanisms.

Diffraction Techniques in Structural Biology

PubMed Central

Egli, Martin

2016-01-01

A detailed understanding of chemical and biological function and the mechanisms underlying the molecular activities ultimately requires atomic-resolution structural data. Diffraction-based techniques such as single-crystal X-ray crystallography, electron microscopy, and neutron diffraction are well established and they have paved the road to the stunning successes of modern-day structural biology. The major advances achieved in the last 20 years in all aspects of structural research, including sample preparation, crystallization, the construction of synchrotron and spallation sources, phasing approaches, and high-speed computing and visualization, now provide specialists and nonspecialists alike with a steady flow of molecular images of unprecedented detail. The present unit combines a general overview of diffraction methods with a detailed description of the process of a single-crystal X-ray structure determination experiment, from chemical synthesis or expression to phasing and refinement, analysis, and quality control. For novices it may serve as a stepping-stone to more in-depth treatises of the individual topics. Readers relying on structural information for interpreting functional data may find it a useful consumer guide. PMID:27248784

Period doubling induced by thermal noise amplification in genetic circuits.

PubMed

Ruocco, G; Fratalocchi, A

2014-11-18

Rhythms of life are dictated by oscillations, which take place in a wide rage of biological scales. In bacteria, for example, oscillations have been proven to control many fundamental processes, ranging from gene expression to cell divisions. In genetic circuits, oscillations originate from elemental block such as autorepressors and toggle switches, which produce robust and noise-free cycles with well defined frequency. In some circumstances, the oscillation period of biological functions may double, thus generating bistable behaviors whose ultimate origin is at the basis of intense investigations. Motivated by brain studies, we here study an "elemental" genetic circuit, where a simple nonlinear process interacts with a noisy environment. In the proposed system, nonlinearity naturally arises from the mechanism of cooperative stability, which regulates the concentration of a protein produced during a transcription process. In this elemental model, bistability results from the coherent amplification of environmental fluctuations due to a stochastic resonance of nonlinear origin. This suggests that the period doubling observed in many biological functions might result from the intrinsic interplay between nonlinearity and thermal noise.

Diffraction Techniques in Structural Biology

PubMed Central

Egli, Martin

2010-01-01

A detailed understanding of chemical and biological function and the mechanisms underlying the activities ultimately requires atomic-resolution structural data. Diffraction-based techniques such as single-crystal X-ray crystallography, electron microscopy and neutron diffraction are well established and have paved the road to the stunning successes of modern-day structural biology. The major advances achieved in the last 20 years in all aspects of structural research, including sample preparation, crystallization, the construction of synchrotron and spallation sources, phasing approaches and high-speed computing and visualization, now provide specialists and non-specialists alike with a steady flow of molecular images of unprecedented detail. The present chapter combines a general overview of diffraction methods with a step-by-step description of the process of a single-crystal X-ray structure determination experiment, from chemical synthesis or expression to phasing and refinement, analysis and quality control. For novices it may serve as a stepping-stone to more in-depth treatises of the individual topics. Readers relying on structural information for interpreting functional data may find it a useful consumer guide. PMID:20517991

Diffraction Techniques in Structural Biology.

PubMed

Egli, Martin

2016-06-01

A detailed understanding of chemical and biological function and the mechanisms underlying the molecular activities ultimately requires atomic-resolution structural data. Diffraction-based techniques such as single-crystal X-ray crystallography, electron microscopy, and neutron diffraction are well established and they have paved the road to the stunning successes of modern-day structural biology. The major advances achieved in the last twenty years in all aspects of structural research, including sample preparation, crystallization, the construction of synchrotron and spallation sources, phasing approaches, and high-speed computing and visualization, now provide specialists and nonspecialists alike with a steady flow of molecular images of unprecedented detail. The present unit combines a general overview of diffraction methods with a detailed description of the process of a single-crystal X-ray structure determination experiment, from chemical synthesis or expression to phasing and refinement, analysis, and quality control. For novices it may serve as a stepping-stone to more in-depth treatises of the individual topics. Readers relying on structural information for interpreting functional data may find it a useful consumer guide. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

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.

The effect of music performance on the transcriptome of professional musicians.

PubMed

Kanduri, Chakravarthi; Kuusi, Tuire; Ahvenainen, Minna; Philips, Anju K; Lähdesmäki, Harri; Järvelä, Irma

2015-03-25

Music performance by professional musicians involves a wide-spectrum of cognitive and multi-sensory motor skills, whose biological basis is unknown. Several neuroscientific studies have demonstrated that the brains of professional musicians and non-musicians differ structurally and functionally and that musical training enhances cognition. However, the molecules and molecular mechanisms involved in music performance remain largely unexplored. Here, we investigated the effect of music performance on the genome-wide peripheral blood transcriptome of professional musicians by analyzing the transcriptional responses after a 2-hr concert performance and after a 'music-free' control session. The up-regulated genes were found to affect dopaminergic neurotransmission, motor behavior, neuronal plasticity, and neurocognitive functions including learning and memory. Particularly, candidate genes such as SNCA, FOS and DUSP1 that are involved in song perception and production in songbirds, were identified, suggesting an evolutionary conservation in biological processes related to sound perception/production. Additionally, modulation of genes related to calcium ion homeostasis, iron ion homeostasis, glutathione metabolism, and several neuropsychiatric and neurodegenerative diseases implied that music performance may affect the biological pathways that are otherwise essential for the proper maintenance of neuronal function and survival. For the first time, this study provides evidence for the candidate genes and molecular mechanisms underlying music performance.

(Im)Perfect robustness and adaptation of metabolic networks subject to metabolic and gene-expression regulation: marrying control engineering with metabolic control analysis

PubMed Central

2013-01-01

Background Metabolic control analysis (MCA) and supply–demand theory have led to appreciable understanding of the systems properties of metabolic networks that are subject exclusively to metabolic regulation. Supply–demand theory has not yet considered gene-expression regulation explicitly whilst a variant of MCA, i.e. Hierarchical Control Analysis (HCA), has done so. Existing analyses based on control engineering approaches have not been very explicit about whether metabolic or gene-expression regulation would be involved, but designed different ways in which regulation could be organized, with the potential of causing adaptation to be perfect. Results This study integrates control engineering and classical MCA augmented with supply–demand theory and HCA. Because gene-expression regulation involves time integration, it is identified as a natural instantiation of the ‘integral control’ (or near integral control) known in control engineering. This study then focuses on robustness against and adaptation to perturbations of process activities in the network, which could result from environmental perturbations, mutations or slow noise. It is shown however that this type of ‘integral control’ should rarely be expected to lead to the ‘perfect adaptation’: although the gene-expression regulation increases the robustness of important metabolite concentrations, it rarely makes them infinitely robust. For perfect adaptation to occur, the protein degradation reactions should be zero order in the concentration of the protein, which may be rare biologically for cells growing steadily. Conclusions A proposed new framework integrating the methodologies of control engineering and metabolic and hierarchical control analysis, improves the understanding of biological systems that are regulated both metabolically and by gene expression. In particular, the new approach enables one to address the issue whether the intracellular biochemical networks that have been and are being identified by genomics and systems biology, correspond to the ‘perfect’ regulatory structures designed by control engineering vis-à-vis optimal functions such as robustness. To the extent that they are not, the analyses suggest how they may become so and this in turn should facilitate synthetic biology and metabolic engineering. PMID:24261908

MeSH-informed enrichment analysis and MeSH-guided semantic similarity among functional terms and gene products in chicken

USDA-ARS?s Scientific Manuscript database

Such Biomedical vocabularies and ontologies aid in recapitulating biological knowledge. The annotation of gene products is mainly accelerated by Gene Ontology (GO) and more recently by Medical Subject Headings (MeSH). MeSH is the National Library of Medicine's controlled vocabulary and it is making ...

What makes closed ecological systems sustainable?

NASA Astrophysics Data System (ADS)

Gitelson, I.; Degermendzhy, A.; Rodicheva, E.

A closed ecosystem has some properties that an open systems lacks. Let us consider the ones that increase the sustainability of an ecosystem. The common feature of biological and physicochemical life support systems is that basically they are both catalytic. There are two fundamental properties distinguishing biological systems: 1) they are auto-catalytic: their catalysts - enzymes of protein nature - are continuously reproduced when the system functions; 2) the program of every process performed by enzymes and the program of their reproduction are inherent in the biological system itself - in the totality of genomes of the species involved in the functioning of the ecosystem. Actually, one cell with the genome capable of the phenotypic realization is enough for the self- restoration of the function performed by the cells of this species in the ecosystem. The multi-cellular organisms with stem cells are constantly ready to repair themselves by intensifying the continuous process of regeneration. We (Gitelson) have made a quantitative investigation of this process by studying the regeneration and reparation of erythrocytes in mammals. The continuous microalgal culture of Chlorella vulgaris was taken to investigate quantitatively the similar functional process of self-restoration in unicellular algae (Rodicheva). Based on the data obtained, we proposed a mathematical model of the restoration process in the cell population that has suffered an acute radiation damage. Besides these general biological mechanisms responsible for their sustainability, closed systems also possess specific features enhancing their stability. They are as follows: 1. Nutrients cannot leave the system. 2. The metabolic pathways of the material cycling are closed. 3. The rates of interlink metabolism are in conformity with each other due to their mutual limitation. We present the data obtained in the Bios-3 experiments that prove the efficiency of this mechanism as a factor of the sustainability. The factors that reduce the sustainability of a CES are as follows: the range of ambient physicochemical parameters compatible with life is rather narrow and it takes rather a long time for the system to restore itself if damage is done to its relatively long-lived species, such as higher plants. A specific property of a small CES is that humans inhabiting it must perform a deterministic control. Our experiments in Bios-3 proved that this control is quite feasible and that it effectively increases the stability of the system. Thus, we can predict that humanity may perform the function of control in the Earth's biosphere in the course of its transformation into the noosphere. * "This work was made possible in part by Award No. REC-002 of the U.S. Civilian Research &Development Foundation for the Independent States of the Former Union (CRDF) and RF Ministry of Education."

Biological consequences of environmental control through housing.

PubMed Central

Lee, D H

1975-01-01

Housing was originally devised as a control of the thermal environment, but numerous other functions have been added with resulting competition and confusion. Current design gives insufficient attention to thermal factors and relies upon supplementary heating and cooling to compensate for faults. These are wasteful of energy, and the exhaust from air conditioners adds to the heat island conditions in city cores. The impact of consumerism on domestic space and the importance of personal space and privacy are reviewed. PMID:1157791

Multifunctional and biologically active matrices from multicomponent polymeric solutions

NASA Technical Reports Server (NTRS)

Kiick, Kristi L. (Inventor); Yamaguchi, Nori (Inventor)

2010-01-01

The present invention relates to a biologically active functionalized electrospun matrix to permit immobilization and long-term delivery of biologically active agents. In particular the invention relates to a functionalized polymer matrix comprising a matrix polymer, a compatibilizing polymer and a biomolecule or other small functioning molecule. In certain aspects the electrospun polymer fibers comprise at least one biologically active molecule functionalized with low molecular weight heparin. Examples of active molecules that may be used with the multicomponent polymer of the invention include, for example, a drug, a biopolymer, for example a growth factor, a protein, a peptide, a nucleotide, a polysaccharide, a biological macromolecule or the like. The invention is further directed to the formation of functionalized crosslinked matrices, such as hydrogels, that include at least one functionalized compatibilizing polymer capable of assembly.

A laser pointer driven microheater for precise local heating and conditional gene regulation in vivo. Microheater driven gene regulation in zebrafish.

PubMed

Placinta, Mike; Shen, Meng-Chieh; Achermann, Marc; Karlstrom, Rolf O

2009-12-30

Tissue heating has been employed to study a variety of biological processes, including the study of genes that control embryonic development. Conditional regulation of gene expression is a particularly powerful approach for understanding gene function. One popular method for mis-expressing a gene of interest employs heat-inducible heat shock protein (hsp) promoters. Global heat shock of hsp-promoter-containing transgenic animals induces gene expression throughout all tissues, but does not allow for spatial control. Local heating allows for spatial control of hsp-promoter-driven transgenes, but methods for local heating are cumbersome and variably effective. We describe a simple, highly controllable, and versatile apparatus for heating biological tissue and other materials on the micron-scale. This microheater employs micron-scale fiber optics and uses an inexpensive laser-pointer as a power source. Optical fibers can be pulled on a standard electrode puller to produce tips of varying sizes that can then be used to reliably heat 20-100 mum targets. We demonstrate precise spatiotemporal control of hsp70l:GFP transgene expression in a variety of tissue types in zebrafish embryos and larvae. We also show how this system can be employed as part of a new method for lineage tracing that would greatly facilitate the study of organogenesis and tissue regulation at any time in the life cycle. This versatile and simple local heater has broad utility for the study of gene function and for lineage tracing. This system could be used to control hsp-driven gene expression in any organism simply by bringing the fiber optic tip in contact with the tissue of interest. Beyond these uses for the study of gene function, this device has wide-ranging utility in materials science and could easily be adapted for therapeutic purposes in humans.

Design methodology and results evaluation of a heating functionality in modular lab-on-chip systems

NASA Astrophysics Data System (ADS)

Streit, Petra; Nestler, Joerg; Shaporin, Alexey; Graunitz, Jenny; Otto, Thomas

2018-06-01

Lab-on-a-chip (LoC) systems offer the opportunity of fast and customized biological analyses executed at the ‘point-of-need’ without expensive lab equipment. Some biological processes need a temperature treatment. Therefore, it is important to ensure a defined and stable temperature distribution in the biosensor area. An integrated heating functionality is realized with discrete resistive heating elements including temperature measurement. The focus of this contribution is a design methodology and evaluation technique of the temperature distribution in the biosensor area with regard to the thermal-electrical behaviour of the heat sources. Furthermore, a sophisticated control of the biosensor temperature is proposed. A finite element (FE) model with one and more integrated heat sources in a polymer-based LoC system is used to investigate the impact of the number and arrangement of heating elements on the temperature distribution around the heating elements and in the biosensor area. Based on this model, various LOC systems are designed and fabricated. Electrical characterization of the heat sources and independent temperature measurements with infrared technique are performed to verify the model parameters and prove the simulation approach. The FE model and the proposed methodology is the foundation for optimization and evaluation of new designs with regard to temperature requirements of the biosensor. Furthermore, a linear dependency of the heater temperature on the electric current is demonstrated in the targeted temperature range of 20 °C to 70 °C enabling the usage of the heating functionality for biological reactions requiring a steady-state temperature up to 70 °C. The correlation between heater and biosensor area temperature is derived for a direct control through the heating current.

Identification of differentially expressed genes from Trichoderma harzianum during growth on cell wall of Fusarium solani as a tool for biotechnological application

PubMed Central

2013-01-01

Background The species of T. harzianum are well known for their biocontrol activity against many plant pathogens. However, there is a lack of studies concerning its use as a biological control agent against F. solani, a pathogen involved in several crop diseases. In this study, we have used subtractive library hybridization (SSH) and quantitative real-time PCR (RT-qPCR) techniques in order to explore changes in T. harzianum genes expression during growth on cell wall of F. solani (FSCW) or glucose. RT-qPCR was also used to examine the regulation of 18 genes, potentially involved in biocontrol, during confrontation between T. harzianum and F. solani. Results Data obtained from two subtractive libraries were compared after annotation using the Blast2GO suite. A total of 417 and 78 readable EST sequence were annotated in the FSCW and glucose libraries, respectively. Functional annotation of these genes identified diverse biological processes and molecular functions required during T. harzianum growth on FSCW or glucose. We identified various genes of biotechnological value encoding to proteins which function such as transporters, hydrolytic activity, adherence, appressorium development and pathogenesis. Fifteen genes were up-regulated and sixteen were down-regulated at least at one-time point during growth of T. harzianum in FSCW. During the confrontation assay most of the genes were up-regulated, mainly after contact, when the interaction has been established. Conclusions This study demonstrates that T. harzianum expressed different genes when grown on FSCW compared to glucose. It provides insights into the mechanisms of gene expression involved in mycoparasitism of T. harzianum against F. solani. The identification and evaluation of these genes may contribute to the development of an efficient biological control agent. PMID:23497274

Identification of differentially expressed genes from Trichoderma harzianum during growth on cell wall of Fusarium solani as a tool for biotechnological application.

PubMed

Vieira, Pabline Marinho; Coelho, Alexandre Siqueira Guedes; Steindorff, Andrei Stecca; de Siqueira, Saulo José Linhares; Silva, Roberto do Nascimento; Ulhoa, Cirano José

2013-03-15

The species of T. harzianum are well known for their biocontrol activity against many plant pathogens. However, there is a lack of studies concerning its use as a biological control agent against F. solani, a pathogen involved in several crop diseases. In this study, we have used subtractive library hybridization (SSH) and quantitative real-time PCR (RT-qPCR) techniques in order to explore changes in T. harzianum genes expression during growth on cell wall of F. solani (FSCW) or glucose. RT-qPCR was also used to examine the regulation of 18 genes, potentially involved in biocontrol, during confrontation between T. harzianum and F. solani. Data obtained from two subtractive libraries were compared after annotation using the Blast2GO suite. A total of 417 and 78 readable EST sequence were annotated in the FSCW and glucose libraries, respectively. Functional annotation of these genes identified diverse biological processes and molecular functions required during T. harzianum growth on FSCW or glucose. We identified various genes of biotechnological value encoding to proteins which function such as transporters, hydrolytic activity, adherence, appressorium development and pathogenesis. Fifteen genes were up-regulated and sixteen were down-regulated at least at one-time point during growth of T. harzianum in FSCW. During the confrontation assay most of the genes were up-regulated, mainly after contact, when the interaction has been established. This study demonstrates that T. harzianum expressed different genes when grown on FSCW compared to glucose. It provides insights into the mechanisms of gene expression involved in mycoparasitism of T. harzianum against F. solani. The identification and evaluation of these genes may contribute to the development of an efficient biological control agent.

Simulations in Medicine and Biology: Insights and perspectives

NASA Astrophysics Data System (ADS)

Spyrou, George M.

2015-01-01

Modern medicine and biology have been transformed into quantitative sciences of high complexity, with challenging objectives. The aims of medicine are related to early diagnosis, effective therapy, accurate intervention, real time monitoring, procedures/systems/instruments optimization, error reduction, and knowledge extraction. Concurrently, following the explosive production of biological data concerning DNA, RNA, and protein biomolecules, a plethora of questions has been raised in relation to their structure and function, the interactions between them, their relationships and dependencies, their regulation and expression, their location, and their thermodynamic characteristics. Furthermore, the interplay between medicine and biology gives rise to fields like molecular medicine and systems biology which are further interconnected with physics, mathematics, informatics, and engineering. Modelling and simulation is a powerful tool in the fields of Medicine and Biology. Simulating the phenomena hidden inside a diagnostic or therapeutic medical procedure, we are able to obtain control on the whole system and perform multilevel optimization. Furthermore, modelling and simulation gives insights in the various scales of biological representation, facilitating the understanding of the huge amounts of derived data and the related mechanisms behind them. Several examples, as well as the insights and the perspectives of simulations in biomedicine will be presented.

Synthetic Morphogenesis.

PubMed

Teague, Brian P; Guye, Patrick; Weiss, Ron

2016-09-01

Throughout biology, function is intimately linked with form. Across scales ranging from subcellular to multiorganismal, the identity and organization of a biological structure's subunits dictate its properties. The field of molecular morphogenesis has traditionally been concerned with describing these links, decoding the molecular mechanisms that give rise to the shape and structure of cells, tissues, organs, and organisms. Recent advances in synthetic biology promise unprecedented control over these molecular mechanisms; this opens the path to not just probing morphogenesis but directing it. This review explores several frontiers in the nascent field of synthetic morphogenesis, including programmable tissues and organs, synthetic biomaterials and programmable matter, and engineering complex morphogenic systems de novo. We will discuss each frontier's objectives, current approaches, constraints and challenges, and future potential. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

Microengineering in cardiovascular research: new developments and translational applications.

PubMed

Chan, Juliana M; Wong, Keith H K; Richards, Arthur Mark; Drum, Chester L

2015-04-01

Microfluidic, cellular co-cultures that approximate macro-scale biology are important tools for refining the in vitro study of organ-level function and disease. In recent years, advances in technical fabrication and biological integration have provided new insights into biological phenomena, improved diagnostic measurements, and made major steps towards de novo tissue creation. Here we review applications of these technologies specific to the cardiovascular field, emphasizing three general categories of use: reductionist vascular models, tissue-engineered vascular models, and point-of-care diagnostics. With continued progress in the ability to purposefully control microscale environments, the detailed study of both primary and cultured cells may find new relevance in the general cardiovascular research community. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Payao: a community platform for SBML pathway model curation

PubMed Central

Matsuoka, Yukiko; Ghosh, Samik; Kikuchi, Norihiro; Kitano, Hiroaki

2010-01-01

Summary: Payao is a community-based, collaborative web service platform for gene-regulatory and biochemical pathway model curation. The system combines Web 2.0 technologies and online model visualization functions to enable a collaborative community to annotate and curate biological models. Payao reads the models in Systems Biology Markup Language format, displays them with CellDesigner, a process diagram editor, which complies with the Systems Biology Graphical Notation, and provides an interface for model enrichment (adding tags and comments to the models) for the access-controlled community members. Availability and implementation: Freely available for model curation service at http://www.payaologue.org. Web site implemented in Seaser Framework 2.0 with S2Flex2, MySQL 5.0 and Tomcat 5.5, with all major browsers supported. Contact: kitano@sbi.jp PMID:20371497

Cadmium-containing quantum dots: properties, applications, and toxicity.

PubMed

Mo, Dan; Hu, Liang; Zeng, Guangming; Chen, Guiqiu; Wan, Jia; Yu, Zhigang; Huang, Zhenzhen; He, Kai; Zhang, Chen; Cheng, Min

2017-04-01

The marriage of biology with nanomaterials has significantly accelerated advancement of biological techniques, profoundly facilitating practical applications in biomedical fields. With unique optical properties (e.g., tunable broad excitation, narrow emission spectra, robust photostability, and high quantum yield), fluorescent quantum dots (QDs) have been reasonably functionalized with controllable interfaces and extensively used as a new class of optical probe in biological researches. In this review, we summarize the recent progress in synthesis and properties of QDs. Moreover, we provide an overview of the outstanding potential of QDs for biomedical research and innovative methods of drug delivery. Specifically, the applications of QDs as novel fluorescent nanomaterials for biomedical sensing and imaging have been detailedly highlighted and discussed. In addition, recent concerns on potential toxicity of QDs are also introduced, ranging from cell researches to animal models.

Connective tissue growth factor (CTGF) from basics to clinics.

PubMed

Ramazani, Yasaman; Knops, Noël; Elmonem, Mohamed A; Nguyen, Tri Q; Arcolino, Fanny Oliveira; van den Heuvel, Lambert; Levtchenko, Elena; Kuypers, Dirk; Goldschmeding, Roel

2018-03-21

Connective tissue growth factor, also known as CCN2, is a cysteine-rich matricellular protein involved in the control of biological processes, such as cell proliferation, differentiation, adhesion and angiogenesis, as well as multiple pathologies, such as tumor development and tissue fibrosis. Here, we describe the molecular and biological characteristics of CTGF, its regulation and various functions in the spectrum of development and regeneration to fibrosis. We further outline the preclinical and clinical studies concerning compounds targeting CTGF in various pathologies with the focus on heart, lung, liver, kidney and solid organ transplantation. Finally, we address the advances and pitfalls of translational fibrosis research and provide suggestions to move towards a better management of fibrosis. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Molecular control of steady-state dendritic cell maturation and immune homeostasis.

PubMed

Hammer, Gianna Elena; Ma, Averil

2013-01-01

Dendritic cells (DCs) are specialized sentinels responsible for coordinating adaptive immunity. This function is dependent upon coupled sensitivity to environmental signs of inflammation and infection to cellular maturation-the programmed alteration of DC phenotype and function to enhance immune cell activation. Although DCs are thus well equipped to respond to pathogens, maturation triggers are not unique to infection. Given that immune cells are exquisitely sensitive to the biological functions of DCs, we now appreciate that multiple layers of suppression are required to restrict the environmental sensitivity, cellular maturation, and even life span of DCs to prevent aberrant immune activation during the steady state. At the same time, steady-state DCs are not quiescent but rather perform key functions that support homeostasis of numerous cell types. Here we review these functions and molecular mechanisms of suppression that control steady-state DC maturation. Corruption of these steady-state operatives has diverse immunological consequences and pinpoints DCs as potent drivers of autoimmune and inflammatory disease.

Pan-Nematoda Transcriptomic Elucidation of Essential Intestinal Functions and Therapeutic Targets With Broad Potential

PubMed Central

Wang, Qi; Rosa, Bruce A.; Jasmer, Douglas P.; Mitreva, Makedonka

2015-01-01

The nematode intestine is continuous with the outside environment, making it easily accessible to anthelmintics for parasite control, but the development of new therapeutics is impeded by limited knowledge of nematode intestinal cell biology. We established the most comprehensive nematode intestinal functional database to date by generating transcriptional data from the dissected intestines of three parasitic nematodes spanning the phylum, and integrating the results with the whole proteomes of 10 nematodes (including 9 pathogens of humans or animals) and 3 host species and 2 outgroup species. We resolved 10,772 predicted nematode intestinal protein families (IntFams), and studied their presence and absence within the different lineages (births and deaths) among nematodes. Conserved intestinal cell functions representing ancestral functions of evolutionary importance were delineated, and molecular features useful for selective therapeutic targeting were identified. Molecular patterns conserved among IntFam proteins demonstrated large potential as therapeutic targets to inhibit intestinal cell functions with broad applications towards treatment and control of parasitic nematodes. PMID:26501106

Impact of Release Rates on the Effectiveness of Augmentative Biological Control Agents

PubMed Central

Crowder, David W.

2007-01-01

To access the effect of augmentative biological control agents, 31 articles were reviewed that investigated the impact of release rates of 35 augmentative biological control agents on the control of 42 arthropod pests. In 64% of the cases, the release rate of the biological control agent did not significantly affect the density or mortality of the pest insect. Results where similar when parasitoidsor predators were utilized as the natural enemy. Within any order of natural enemy, there were more cases where release rates did not affect augmentative biological control than cases where release rates were significant. There were more cases in which release rates did not affect augmentative biological control when pests were from the orders Hemiptera, Acari, or Diptera, but not with pests from the order Lepidoptera. In most cases, there was an optimal release rate that produced effective control of a pest species. This was especially true when predators were used as a biological control agent. Increasing the release rate above the optimal rate did not improve control of the pest and thus would be economically detrimental. Lower release rates were of ten optimal when biological control was used in conjunction with insecticides. In many cases, the timing and method of biological control applications were more significant factors impacting the effectiveness of biological control than the release rate. Additional factors that may limit the relative impact of release rates include natural enemy fecundity, establishment rates, prey availability, dispersal, and cannibalism. PMID:20307240

Molecular Velcro constructed from polymer loop brushes showing enhanced adhesion force

NASA Astrophysics Data System (ADS)

Zhou, Tian; Han, Biao; Han, Lin; Li, Christopher; Department of Materials Science; Engineering Team; School of Biomedical Engineering, Science; Health Systems Team

2015-03-01

Molecular Velcro is commonly seen in biological systems as the formation of strong physical entanglement at molecular scale could induce strong adhesion, which is crucial to many biological processes. To mimic this structure, we designed, and fabricated polymer loop brushes using polymer single crystals with desired surface functionality and controlled chain folding. Compared with reported loop brushes fabricated using triblock copolymers, the present loop bushes have precise loop sizes, loop grafting density, and well controlled tethering locations on the solid surface. Atomic force microscopy-based force spectroscopy measurements using a polymer chain coated probe reveal that the adhesion force are significantly enhanced on the loop brush surface as compared with its single-strand counterpart. This study directly shows the effect of polymer brush conformation on their properties, and suggests a promising strategy for advanced polymer surface design.

Notable Expressions: Transcriptional Regulation from Biochemistry to Immunology | Center for Cancer Research

Cancer.gov

Dinah Singer, Ph.D., came to NCI in 1975 as a Postdoctoral Fellow in the Laboratory of Biochemistry, but soon created a career for herself in the Experimental Immunology Branch. Her interest in how genes are regulated to control biological function led her to focus on major histocompatibility complex class I genes (MHC Class I)—molecules critical to immune system function—as a model system for complex regulation of ubiquitously expressed genes across cell types and molecular contexts. Using this system to study the sequence elements and factors that control transcription, her laboratory continues to uncover fundamental principles of gene regulation. In addition to her active research career, Singer has served since 1999 as Director of NCI’s Division of Cancer Biology, which manages a portfolio of over 2,200 grants to extramural investigators.

The Microsoft Biology Foundation Applications for High-Throughput Sequencing

PubMed Central

Mercer, S.

2010-01-01

w9-2 The need for reusable libraries of bioinformatics functions has been recognized for many years and a number of language-specific toolkits have been constructed. Such toolkits have served as valuable nucleation points for the community, promoting the sharing of code and establishing standards. The majority of DNA sequencing machines and many other standard pieces of lab equipment are controlled by PCs using Windows, and a Microsoft genomics toolkit would enable initial processing and quality control to happen closer to the instrumentation and provide opportunities for added-value services within core facilities. The Microsoft Biology Foundation (MBF) is an open source software library, freely available for both commercial and academic use, available as an early-stage betafrom mbf.codeplex.com. This presentation will describe the structure and goals of MBF and demonstrate some of its uses.

Diversity and function of bacterial microbiota in the mosquito holobiont

PubMed Central

2013-01-01

Mosquitoes (Diptera: Culicidae) have been shown to host diverse bacterial communities that vary depending on the sex of the mosquito, the developmental stage, and ecological factors. Some studies have suggested a potential role of microbiota in the nutritional, developmental and reproductive biology of mosquitoes. Here, we present a review of the diversity and functions of mosquito-associated bacteria across multiple variation factors, emphasizing recent findings. Mosquito microbiota is considered in the context of possible extended phenotypes conferred on the insect hosts that allow niche diversification and rapid adaptive evolution in other insects. These kinds of observations have prompted the recent development of new mosquito control methods based on the use of symbiotically-modified mosquitoes to interfere with pathogen transmission or reduce the host life span and reproduction. New opportunities for exploiting bacterial function for vector control are highlighted. PMID:23688194

Transcriptional Mechanisms Underlying Hemoglobin Synthesis

PubMed Central

Katsumura, Koichi R.; DeVilbiss, Andrew W.; Pope, Nathaniel J.; Johnson, Kirby D.; Bresnick, Emery H.

2013-01-01

The physiological switch in expression of the embryonic, fetal, and adult β-like globin genes has garnered enormous attention from investigators interested in transcriptional mechanisms and the molecular basis of hemoglobinopathies. These efforts have led to the discovery of cell type-specific transcription factors, unprecedented mechanisms of transcriptional coregulator function, genome biology principles, unique contributions of nuclear organization to transcription and cell function, and promising therapeutic targets. Given the vast literature accrued on this topic, this article will focus on the master regulator of erythroid cell development and function GATA-1, its associated proteins, and its frontline role in controlling hemoglobin synthesis. GATA-1 is a crucial regulator of genes encoding hemoglobin subunits and heme biosynthetic enzymes. GATA-1-dependent mechanisms constitute an essential regulatory core that nucleates additional mechanisms to achieve the physiological control of hemoglobin synthesis. PMID:23838521

Polymeric Biomaterials: Diverse Functions Enabled by Advances in Macromolecular Chemistry

PubMed Central

Liang, Yingkai; Li, Linqing; Scott, Rebecca A.; Kiick, Kristi L.

2017-01-01

Biomaterials have been extensively used to leverage beneficial outcomes in various therapeutic applications, such as providing spatial and temporal control over the release of therapeutic agents in drug delivery as well as engineering functional tissues and promoting the healing process in tissue engineering and regenerative medicine. This perspective presents important milestones in the development of polymeric biomaterials with defined structures and properties. Contemporary studies of biomaterial design have been reviewed with focus on constructing materials with controlled structure, dynamic functionality, and biological complexity. Examples of these polymeric biomaterials enabled by advanced synthetic methodologies, dynamic chemistry/assembly strategies, and modulated cell-material interactions have been highlighted. As the field of polymeric biomaterials continues to evolve with increased sophistication, current challenges and future directions for the design and translation of these materials are also summarized. PMID:29151616

Artificially Engineered Protein Polymers.

PubMed

Yang, Yun Jung; Holmberg, Angela L; Olsen, Bradley D

2017-06-07

Modern polymer science increasingly requires precise control over macromolecular structure and properties for engineering advanced materials and biomedical systems. The application of biological processes to design and synthesize artificial protein polymers offers a means for furthering macromolecular tunability, enabling polymers with dispersities of ∼1.0 and monomer-level sequence control. Taking inspiration from materials evolved in nature, scientists have created modular building blocks with simplified monomer sequences that replicate the function of natural systems. The corresponding protein engineering toolbox has enabled the systematic development of complex functional polymeric materials across areas as diverse as adhesives, responsive polymers, and medical materials. This review discusses the natural proteins that have inspired the development of key building blocks for protein polymer engineering and the function of these elements in material design. The prospects and progress for scalable commercialization of protein polymers are reviewed, discussing both technology needs and opportunities.

Healthy Foundations Study: a randomised controlled trial to evaluate biological embedding of early-life experiences.

PubMed

Gonzalez, Andrea; Catherine, Nicole; Boyle, Michael; Jack, Susan M; Atkinson, Leslie; Kobor, Michael; Sheehan, Debbie; Tonmyr, Lil; Waddell, Charlotte; MacMillan, Harriet L

2018-01-26

Adverse early experiences are associated with long-lasting disruptions in physiology, development and health. These experiences may be 'biologically embedded' into molecular and genomic systems that determine later expressions of vulnerability. Most studies to date have not examined whether preventive interventions can potentially reverse biological embedding. The Nurse-Family Partnership (NFP) is an evidence-based intervention with demonstrated efficacy in improving prenatal health, parenting and child functioning. The Healthy Foundations Study is an innovative birth cohort which will evaluate the impact of the NFP on biological outcomes of mothers and their infants. Starting in 2013, up to 400 pregnant mothers and their newborns were recruited from the British Columbia Healthy Connections Project-a randomised controlled trial of the NFP, and will be followed to child aged 2 years. Women were recruited prior to 28 weeks' gestation and then individually randomised to receive existing services (comparison group) or NFP plus existing services (intervention group). Hair samples are collected from mothers at baseline and 2 months post partum to measure physiological stress. Saliva samples are collected from infants during all visits for analyses of stress and immune function. Buccal swabs are collected from infants at 2 and 24 months to assess DNA methylation. Biological samples will be related to child outcome measures at age 2 years. The study received ethical approval from seven research ethics boards. Findings from this study will be shared broadly with the research community through peer-reviewed publications, and conference presentations, as well as seminars with our policy partners and relevant healthcare providers. The outcomes of this study will provide all stakeholders with important information regarding how early adversity may lead to health and behavioural disparities and how these may be altered through early interventions. NCT01672060; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Filtering genetic variants and placing informative priors based on putative biological function.

PubMed

Friedrichs, Stefanie; Malzahn, Dörthe; Pugh, Elizabeth W; Almeida, Marcio; Liu, Xiao Qing; Bailey, Julia N

2016-02-03

High-density genetic marker data, especially sequence data, imply an immense multiple testing burden. This can be ameliorated by filtering genetic variants, exploiting or accounting for correlations between variants, jointly testing variants, and by incorporating informative priors. Priors can be based on biological knowledge or predicted variant function, or even be used to integrate gene expression or other omics data. Based on Genetic Analysis Workshop (GAW) 19 data, this article discusses diversity and usefulness of functional variant scores provided, for example, by PolyPhen2, SIFT, or RegulomeDB annotations. Incorporating functional scores into variant filters or weights and adjusting the significance level for correlations between variants yielded significant associations with blood pressure traits in a large family study of Mexican Americans (GAW19 data set). Marker rs218966 in gene PHF14 and rs9836027 in MAP4 significantly associated with hypertension; additionally, rare variants in SNUPN significantly associated with systolic blood pressure. Variant weights strongly influenced the power of kernel methods and burden tests. Apart from variant weights in test statistics, prior weights may also be used when combining test statistics or to informatively weight p values while controlling false discovery rate (FDR). Indeed, power improved when gene expression data for FDR-controlled informative weighting of association test p values of genes was used. Finally, approaches exploiting variant correlations included identity-by-descent mapping and the optimal strategy for joint testing rare and common variants, which was observed to depend on linkage disequilibrium structure.

Restoration of voice function by using biological feedback in laryngeal and hypopharyngeal carcinoma patients

NASA Astrophysics Data System (ADS)

Choinzonov, E. L.; Balatskaya, L. N.; Chizhevskaya, S. Yu.; Meshcheryakov, R. V.; Kostyuchenko, E. Yu.; Ivanova, T. A.

2016-08-01

The aim of the research is to develop and introduce a new technique of post-laryngectomy voice rehabilitation of laryngeal and hypopharyngeal carcinoma patients. The study involves comparing and analyzing 82 cases of voice function restoration by using biological feedback based on mathematical modeling of voice production. The advantage of the modern technology-based method in comparison with the conventional one is proved. Restoration of voice function using biofeedback allows taking into account patient's abilities, adjusting parameters of voice trainings, and controlling their efficiency in real-time mode. The data obtained indicate that the new method contributes to the rapid inclusion of self-regulation mechanisms of the body and results in the overall success rate of voice rehabilitation in totally laryngectomized patients reaching 92%, which reduces the rehabilitation period to 18 days, compared to 86% and 38 days in the control group, respectively. Restoration of disturbed functions after successful treatment is an important task of rehabilitation and is crucial in terms of the quality of cancer patients' lives. To assess life quality of laryngeal cancer patients, the EORTC Quality of Life Core Questionnaire (QLQ-C30), and head and neck module (QLQ-H&N35) were used. The analyzed results proved that the technique of biofeedback voice restoration significantly improves the quality of life of laryngectomized patients. It allows reducing the number of disabled people, restoring patients' ability to work-related activities, and significantly improving social adaptation of these patients.

Cellular homeostasis in fungi: impact on the aging process.

PubMed

Scheckhuber, Christian Q; Hamann, Andrea; Brust, Diana; Osiewacz, Heinz D

2012-01-01

Cellular quality control pathways are needed for maintaining the biological function of organisms. If these pathways become compromised, the results are usually highly detrimental. Functional impairments of cell components can lead to diseases and in extreme cases to organismal death. Dysfunction of cells can be induced by a number of toxic by-products that are formed during metabolic activity, like reactive oxygen and nitrogen species, for example. A key source of reactive oxygen species (ROS) are the organelles of oxidative phosphorylation, mitochondria. Therefore mitochondrial function is also directly affected by ROS, especially if there is a compromised ROS-scavenging capacity. Biological systems therefore depend on several lines of defence to counteract the toxic effects of ROS and other damaging agents. The first level is active at the molecular level and consists of various proteases that bind and degrade abnormally modified and / or aggregated mitochondrial proteins. The second level is concerned with maintaining the quality of whole mitochondria. Among the pathways of this level are mitochondrial dynamics and autophagy (mitophagy). Mitochondrial dynamics describes the time-dependent fusion and fission of mitochondria. It is argued that this kind of organellar dynamics has the power to restore the function of impaired organelles by content mixing with intact organelles. If the first and second lines of defence against damage fail and mitochondria become damaged too severely, there is the option to remove affected cells before they can elicit more damage to their surrounding environment by apoptosis. This form of programmed cell death is strictly regulated by a complex network of interacting components and can be divided into mitochondria-dependent and mitochondria-independent modes of action. In this review we give an overview on various biological quality control systems in fungi (yeasts and filamentous fungi) with an emphasis on autophagy (mitophagy) and apoptosis and how these pathways allow fungal organisms to maintain a balanced cellular homeostasis.

Computing biological functions using BioΨ, a formal description of biological processes based on elementary bricks of actions

PubMed Central

Pérès, Sabine; Felicori, Liza; Rialle, Stéphanie; Jobard, Elodie; Molina, Franck

2010-01-01

Motivation: In the available databases, biological processes are described from molecular and cellular points of view, but these descriptions are represented with text annotations that make it difficult to handle them for computation. Consequently, there is an obvious need for formal descriptions of biological processes. Results: We present a formalism that uses the BioΨ concepts to model biological processes from molecular details to networks. This computational approach, based on elementary bricks of actions, allows us to calculate on biological functions (e.g. process comparison, mapping structure–function relationships, etc.). We illustrate its application with two examples: the functional comparison of proteases and the functional description of the glycolysis network. This computational approach is compatible with detailed biological knowledge and can be applied to different kinds of systems of simulation. Availability: www.sysdiag.cnrs.fr/publications/supplementary-materials/BioPsi_Manager/ Contact: sabine.peres@sysdiag.cnrs.fr; franck.molina@sysdiag.cnrs.fr Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20448138

Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? What Really Constitutes the Study of "Systems Biology" and How Might Such an Approach Facilitate Vaccine Design.

PubMed

Germain, Ronald N

2017-10-16

A dichotomy exists in the field of vaccinology about the promise versus the hype associated with application of "systems biology" approaches to rational vaccine design. Some feel it is the only way to efficiently uncover currently unknown parameters controlling desired immune responses or discover what elements actually mediate these responses. Others feel that traditional experimental, often reductionist, methods for incrementally unraveling complex biology provide a more solid way forward, and that "systems" approaches are costly ways to collect data without gaining true insight. Here I argue that both views are inaccurate. This is largely because of confusion about what can be gained from classical experimentation versus statistical analysis of large data sets (bioinformatics) versus methods that quantitatively explain emergent properties of complex assemblies of biological components, with the latter reflecting what was previously called "physiology." Reductionist studies will remain essential for generating detailed insight into the functional attributes of specific elements of biological systems, but such analyses lack the power to provide a quantitative and predictive understanding of global system behavior. But by employing (1) large-scale screening methods for discovery of unknown components and connections in the immune system ( omics ), (2) statistical analysis of large data sets ( bioinformatics ), and (3) the capacity of quantitative computational methods to translate these individual components and connections into models of emergent behavior ( systems biology ), we will be able to better understand how the overall immune system functions and to determine with greater precision how to manipulate it to produce desired protective responses. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Nuclear organization mediates cancer-compromised genetic and epigenetic control.

PubMed

Zaidi, Sayyed K; Fritz, Andrew; Tracy, Kirsten; Gordon, Jonathan; Tye, Coralee; Boyd, Joseph; Van Wijnen, Andre; Nickerson, Jeffrey; Imbalzano, Anthony; Lian, Jane; Stein, Janet; Stein, Gary

2018-05-09

Nuclear organization is functionally linked to genetic and epigenetic regulation of gene expression for biological control and is modified in cancer. Nuclear organization supports cell growth and phenotypic properties of normal and cancer cells by facilitating physiologically responsive interactions of chromosomes, genes and regulatory complexes at dynamic three-dimensional microenvironments. We will review nuclear structure/function relationships that include: 1. Epigenetic bookmarking of genes by phenotypic transcription factors to control fidelity and plasticity of gene expression as cells enter and exit mitosis; 2. Contributions of chromatin remodeling to breast cancer nuclear morphology, metabolism and effectiveness of chemotherapy; 3. Relationships between fidelity of nuclear organization and metastasis of breast cancer to bone; 4. Dynamic modifications of higher-order inter- and intra-chromosomal interactions in breast cancer cells; 5. Coordinate control of cell growth and phenotype by tissue-specific transcription factors; 6. Oncofetal epigenetic control by bivalent histone modifications that are functionally related to sustaining the stem cell phenotype; and 7. Noncoding RNA-mediated regulation in the onset and progression of breast cancer. The discovery of components to nuclear organization that are functionally related to cancer and compromise gene expression have the potential for translation to innovative cancer diagnosis and targeted therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Average of delta: a new quality control tool for clinical laboratories.

PubMed

Jones, Graham R D

2016-01-01

Average of normals is a tool used to control assay performance using the average of a series of results from patients' samples. Delta checking is a process of identifying errors in individual patient results by reviewing the difference from previous results of the same patient. This paper introduces a novel alternate approach, average of delta, which combines these concepts to use the average of a number of sequential delta values to identify changes in assay performance. Models for average of delta and average of normals were developed in a spreadsheet application. The model assessed the expected scatter of average of delta and average of normals functions and the effect of assay bias for different values of analytical imprecision and within- and between-subject biological variation and the number of samples included in the calculations. The final assessment was the number of patients' samples required to identify an added bias with 90% certainty. The model demonstrated that with larger numbers of delta values, the average of delta function was tighter (lower coefficient of variation). The optimal number of samples for bias detection with average of delta was likely to be between 5 and 20 for most settings and that average of delta outperformed average of normals when the within-subject biological variation was small relative to the between-subject variation. Average of delta provides a possible additional assay quality control tool which theoretical modelling predicts may be more valuable than average of normals for analytes where the group biological variation is wide compared with within-subject variation and where there is a high rate of repeat testing in the laboratory patient population. © The Author(s) 2015.