WorldWideScience

Sample records for expanding biological functions

  1. An expanded role for microbial physiology in metabolic engineering and functional genomics: moving towards systems biology

    DEFF Research Database (Denmark)

    Nielsen, Jens; Olsson, Lisbeth

    2002-01-01

    . With the progress in molecular biology it has become possible to optimize industrial fermentations through introduction of directed genetic modification - an approach referred to as metabolic engineering. Furthermore, as a consequence of large sequencing programs the complete genomic sequence has become available...... for an increasing number of microorganisms. This has resulted in substantial research efforts in assigning function to all identified open reading frames - referred to as functional genomics. In both metabolic engineering and functional genomics there is a trend towards application of a macroscopic view on cell......Microbial physiology has traditionally played a very important role in both fundamental research and in industrial applications of microorganisms. The classical approach in microbial physiology has been to analyze the role of individual components (genes or proteins) in the overall cell function...

  2. Expanding the biological periodic table.

    Science.gov (United States)

    Seravalli, Javier; Ragsdale, Stephen W

    2010-08-27

    Metal ions play an indispensable role in biology, enabling enzymes to perform their functions and lending support to the structures of numerous macromolecules. Despite their prevalence and importance, the metalloproteome is still relatively unexplored. Cvetkovic et al. (2010) now describe an approach to identify metalloproteins on a genome-wide scale. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  3. Synthetic biology expands chemical control of microorganisms

    OpenAIRE

    Ford, Tyler J.; Silver, Pamela A.

    2015-01-01

    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 metabol...

  4. Synthetic biology expands chemical control of microorganisms.

    Science.gov (United States)

    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.

  5. Opportunities for synthetic biology in antibiotics: expanding glycopeptide chemical diversity.

    Science.gov (United States)

    Thaker, Maulik N; Wright, Gerard D

    2015-03-20

    Synthetic biology offers a new path for the exploitation and improvement of natural products to address the growing crisis in antibiotic resistance. All antibiotics in clinical use are facing eventual obsolesce as a result of the evolution and dissemination of resistance mechanisms, yet there are few new drug leads forthcoming from the pharmaceutical sector. Natural products of microbial origin have proven over the past 70 years to be the wellspring of antimicrobial drugs. Harnessing synthetic biology thinking and strategies can provide new molecules and expand chemical diversity of known antibiotic scaffolds to provide much needed new drug leads. The glycopeptide antibiotics offer paradigmatic scaffolds suitable for such an approach. We review these strategies here using the glycopeptides as an example and demonstrate how synthetic biology can expand antibiotic chemical diversity to help address the growing resistance crisis.

  6. Functions in Biological Kind Classification

    Science.gov (United States)

    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…

  7. Expanding the Functional Assessment Model for Naturalistic Intervention Design.

    Science.gov (United States)

    Evans, Ian M.

    2000-01-01

    This article comments on a study that used functional assessment to reduce behavior problems in a child with multiple disabilities (Kern and Vorndran, 2000). It suggests additional principles need to be incorporated into an expanded model if functional assessment is to have a truly positive influence on naturalistic treatment planning. (Contains…

  8. The relativity of biological function.

    Science.gov (United States)

    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.

  9. Post-translational tools expand the scope of synthetic biology.

    Science.gov (United States)

    Olson, Evan J; Tabor, Jeffrey J

    2012-08-01

    Synthetic biology is improving our understanding of and ability to control living organisms. To date, most progress has been made by engineering gene expression. However, computational and genetically encoded tools that allow protein activity and protein-protein interactions to be controlled on their natural time and length scales are emerging. These technologies provide a basis for the construction of post-translational circuits, which are capable of fast, robust and highly spatially resolved signal processing. When combined with their transcriptional and translational counterparts, synthetic post-translational circuits will allow better analysis and control of otherwise intractable biological processes such as cellular differentiation and the growth of tissues. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. The modern theory of biological evolution: an expanded synthesis.

    Science.gov (United States)

    Kutschera, Ulrich; Niklas, Karl J

    2004-06-01

    In 1858, two naturalists, Charles Darwin and Alfred Russel Wallace, independently proposed natural selection as the basic mechanism responsible for the origin of new phenotypic variants and, ultimately, new species. A large body of evidence for this hypothesis was published in Darwin's Origin of Species one year later, the appearance of which provoked other leading scientists like August Weismann to adopt and amplify Darwin's perspective. Weismann's neo-Darwinian theory of evolution was further elaborated, most notably in a series of books by Theodosius Dobzhansky, Ernst Mayr, Julian Huxley and others. In this article we first summarize the history of life on Earth and provide recent evidence demonstrating that Darwin's dilemma (the apparent missing Precambrian record of life) has been resolved. Next, the historical development and structure of the "modern synthesis" is described within the context of the following topics: paleobiology and rates of evolution, mass extinctions and species selection, macroevolution and punctuated equilibrium, sexual reproduction and recombination, sexual selection and altruism, endosymbiosis and eukaryotic cell evolution, evolutionary developmental biology, phenotypic plasticity, epigenetic inheritance and molecular evolution, experimental bacterial evolution, and computer simulations (in silico evolution of digital organisms). In addition, we discuss the expansion of the modern synthesis, embracing all branches of scientific disciplines. It is concluded that the basic tenets of the synthetic theory have survived, but in modified form. These sub-theories require continued elaboration, particularly in light of molecular biology, to answer open-ended questions concerning the mechanisms of evolution in all five kingdoms of life.

  11. The modern theory of biological evolution: an expanded synthesis

    Science.gov (United States)

    Kutschera, Ulrich; Niklas, Karl J.

    In 1858, two naturalists, Charles Darwin and Alfred Russel Wallace, independently proposed natural selection as the basic mechanism responsible for the origin of new phenotypic variants and, ultimately, new species. A large body of evidence for this hypothesis was published in Darwin's Origin of Species one year later, the appearance of which provoked other leading scientists like August Weismann to adopt and amplify Darwin's perspective. Weismann's neo-Darwinian theory of evolution was further elaborated, most notably in a series of books by Theodosius Dobzhansky, Ernst Mayr, Julian Huxley and others. In this article we first summarize the history of life on Earth and provide recent evidence demonstrating that Darwin's dilemma (the apparent missing Precambrian record of life) has been resolved. Next, the historical development and structure of the ``modern synthesis'' is described within the context of the following topics: paleobiology and rates of evolution, mass extinctions and species selection, macroevolution and punctuated equilibrium, sexual reproduction and recombination, sexual selection and altruism, endosymbiosis and eukaryotic cell evolution, evolutionary developmental biology, phenotypic plasticity, epigenetic inheritance and molecular evolution, experimental bacterial evolution, and computer simulations (in silico evolution of digital organisms). In addition, we discuss the expansion of the modern synthesis, embracing all branches of scientific disciplines. It is concluded that the basic tenets of the synthetic theory have survived, but in modified form. These sub-theories require continued elaboration, particularly in light of molecular biology, to answer open-ended questions concerning the mechanisms of evolution in all five kingdoms of life.

  12. CLIC, a tool for expanding biological pathways based on co-expression across thousands of datasets

    Science.gov (United States)

    Li, Yang; Liu, Jun S.; Mootha, Vamsi K.

    2017-01-01

    In recent years, there has been a huge rise in the number of publicly available transcriptional profiling datasets. These massive compendia comprise billions of measurements and provide a special opportunity to predict the function of unstudied genes based on co-expression to well-studied pathways. Such analyses can be very challenging, however, since biological pathways are modular and may exhibit co-expression only in specific contexts. To overcome these challenges we introduce CLIC, CLustering by Inferred Co-expression. CLIC accepts as input a pathway consisting of two or more genes. It then uses a Bayesian partition model to simultaneously partition the input gene set into coherent co-expressed modules (CEMs), while assigning the posterior probability for each dataset in support of each CEM. CLIC then expands each CEM by scanning the transcriptome for additional co-expressed genes, quantified by an integrated log-likelihood ratio (LLR) score weighted for each dataset. As a byproduct, CLIC automatically learns the conditions (datasets) within which a CEM is operative. We implemented CLIC using a compendium of 1774 mouse microarray datasets (28628 microarrays) or 1887 human microarray datasets (45158 microarrays). CLIC analysis reveals that of 910 canonical biological pathways, 30% consist of strongly co-expressed gene modules for which new members are predicted. For example, CLIC predicts a functional connection between protein C7orf55 (FMC1) and the mitochondrial ATP synthase complex that we have experimentally validated. CLIC is freely available at www.gene-clic.org. We anticipate that CLIC will be valuable both for revealing new components of biological pathways as well as the conditions in which they are active. PMID:28719601

  13. CLIC, a tool for expanding biological pathways based on co-expression across thousands of datasets.

    Directory of Open Access Journals (Sweden)

    Yang Li

    2017-07-01

    Full Text Available In recent years, there has been a huge rise in the number of publicly available transcriptional profiling datasets. These massive compendia comprise billions of measurements and provide a special opportunity to predict the function of unstudied genes based on co-expression to well-studied pathways. Such analyses can be very challenging, however, since biological pathways are modular and may exhibit co-expression only in specific contexts. To overcome these challenges we introduce CLIC, CLustering by Inferred Co-expression. CLIC accepts as input a pathway consisting of two or more genes. It then uses a Bayesian partition model to simultaneously partition the input gene set into coherent co-expressed modules (CEMs, while assigning the posterior probability for each dataset in support of each CEM. CLIC then expands each CEM by scanning the transcriptome for additional co-expressed genes, quantified by an integrated log-likelihood ratio (LLR score weighted for each dataset. As a byproduct, CLIC automatically learns the conditions (datasets within which a CEM is operative. We implemented CLIC using a compendium of 1774 mouse microarray datasets (28628 microarrays or 1887 human microarray datasets (45158 microarrays. CLIC analysis reveals that of 910 canonical biological pathways, 30% consist of strongly co-expressed gene modules for which new members are predicted. For example, CLIC predicts a functional connection between protein C7orf55 (FMC1 and the mitochondrial ATP synthase complex that we have experimentally validated. CLIC is freely available at www.gene-clic.org. We anticipate that CLIC will be valuable both for revealing new components of biological pathways as well as the conditions in which they are active.

  14. Expanding the chemical palate of cells by combining systems biology and metabolic engineering.

    Science.gov (United States)

    Curran, Kathleen A; Alper, Hal S

    2012-07-01

    The field of Metabolic Engineering has recently undergone a transformation that has led to a rapid expansion of the chemical palate of cells. Now, it is conceivable to produce nearly any organic molecule of interest using a cellular host. Significant advances have been made in the production of biofuels, biopolymers and precursors, pharmaceuticals and nutraceuticals, and commodity and specialty chemicals. Much of this rapid expansion in the field has been, in part, due to synergies and advances in the area of systems biology. Specifically, the availability of functional genomics, metabolomics and transcriptomics data has resulted in the potential to produce a wealth of new products, both natural and non-natural, in cellular factories. The sheer amount and diversity of this data however, means that uncovering and unlocking novel chemistries and insights is a non-obvious exercise. To address this issue, a number of computational tools and experimental approaches have been developed to help expedite the design process to create new cellular factories. This review will highlight many of the systems biology enabling technologies that have reduced the design cycle for engineered hosts, highlight major advances in the expanded diversity of products that can be synthesized, and conclude with future prospects in the field of metabolic engineering. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Functional evolution of new and expanded attention networks in humans

    Science.gov (United States)

    Patel, Gaurav H.; Yang, Danica; Jamerson, Emery C.; Snyder, Lawrence H.; Corbetta, Maurizio; Ferrera, Vincent P.

    2015-01-01

    Macaques are often used as a model system for invasive investigations of the neural substrates of cognition. However, 25 million years of evolution separate humans and macaques from their last common ancestor, and this has likely substantially impacted the function of the cortical networks underlying cognitive processes, such as attention. We examined the homology of frontoparietal networks underlying attention by comparing functional MRI data from macaques and humans performing the same visual search task. Although there are broad similarities, we found fundamental differences between the species. First, humans have more dorsal attention network areas than macaques, indicating that in the course of evolution the human attention system has expanded compared with macaques. Second, potentially homologous areas in the dorsal attention network have markedly different biases toward representing the contralateral hemifield, indicating that the underlying neural architecture of these areas may differ in the most basic of properties, such as receptive field distribution. Third, despite clear evidence of the temporoparietal junction node of the ventral attention network in humans as elicited by this visual search task, we did not find functional evidence of a temporoparietal junction in macaques. None of these differences were the result of differences in training, experimental power, or anatomical variability between the two species. The results of this study indicate that macaque data should be applied to human models of cognition cautiously, and demonstrate how evolution may shape cortical networks. PMID:26170314

  16. The biological function of consciousness

    Directory of Open Access Journals (Sweden)

    Brian eEarl

    2014-08-01

    Full Text Available This research is an investigation of whether consciousness—one’s ongoing experience—influences one’s behavior and, if so, how. Analysis of the components, structure, properties, and temporal sequences of consciousness has established that, (1 contrary to one’s intuitive understanding, consciousness does not have an active, executive role in determining behavior; (2 consciousness does have a biological function; and (3 consciousness is solely information in various forms. Consciousness is associated with a flexible response mechanism (FRM for decision-making, planning, and generally responding in nonautomatic ways. The FRM generates responses by manipulating information and, to function effectively, its data input must be restricted to task-relevant information. The properties of consciousness correspond to the various input requirements of the FRM; and when important information is missing from consciousness, functions of the FRM are adversely affected; both of which indicate that consciousness is the input data to the FRM. Qualitative and quantitative information (shape, size, location, etc., is incorporated into the input data by a qualia array of colors, sounds, and so on, which makes the input conscious. This view of the biological function of consciousness provides an explanation why we have experiences; why we have emotional and other feelings, and why their loss is associated with poor decision-making; why blindsight patients do not spontaneously initiate responses to events in their blind field; why counter-habitual actions are only possible when the intended action is in mind; and the reason for inattentional blindness.

  17. The biological function of consciousness

    Science.gov (United States)

    Earl, Brian

    2014-01-01

    This research is an investigation of whether consciousness—one's ongoing experience—influences one's behavior and, if so, how. Analysis of the components, structure, properties, and temporal sequences of consciousness has established that, (1) contrary to one's intuitive understanding, consciousness does not have an active, executive role in determining behavior; (2) consciousness does have a biological function; and (3) consciousness is solely information in various forms. Consciousness is associated with a flexible response mechanism (FRM) for decision-making, planning, and generally responding in nonautomatic ways. The FRM generates responses by manipulating information and, to function effectively, its data input must be restricted to task-relevant information. The properties of consciousness correspond to the various input requirements of the FRM; and when important information is missing from consciousness, functions of the FRM are adversely affected; both of which indicate that consciousness is the input data to the FRM. Qualitative and quantitative information (shape, size, location, etc.) are incorporated into the input data by a qualia array of colors, sounds, and so on, which makes the input conscious. This view of the biological function of consciousness provides an explanation why we have experiences; why we have emotional and other feelings, and why their loss is associated with poor decision-making; why blindsight patients do not spontaneously initiate responses to events in their blind field; why counter-habitual actions are only possible when the intended action is in mind; and the reason for inattentional blindness. PMID:25140159

  18. Functional Aspects of Biological Networks

    Science.gov (United States)

    Sneppen, Kim

    2007-03-01

    We discuss biological networks with respect to 1) relative positioning and importance of high degree nodes, 2) function and signaling, 3) logic and dynamics of regulation. Visually the soft modularity of many real world networks can be characterized in terms of number of high and low degrees nodes positioned relative to each other in a landscape analogue with mountains (high-degree nodes) and valleys (low-degree nodes). In these terms biological networks looks like rugged landscapes with separated peaks, hub proteins, which each are roughly as essential as any of the individual proteins on the periphery of the hub. Within each sup-domain of a molecular network one can often identify dynamical feedback mechanisms that falls into combinations of positive and negative feedback circuits. We will illustrate this with examples taken from phage regulation and bacterial uptake and regulation of small molecules. In particular we find that a double negative regulation often are replaced by a single positive link in unrelated organisms with same functional requirements. Overall we argue that network topology primarily reflects functional constraints. References: S. Maslov and K. Sneppen. ``Computational architecture of the yeast regulatory network." Phys. Biol. 2:94 (2005) A. Trusina et al. ``Functional alignment of regulatory networks: A study of temerate phages". Plos Computational Biology 1:7 (2005). J.B. Axelsen et al. ``Degree Landscapes in Scale-Free Networks" physics/0512075 (2005). A. Trusina et al. ``Hierarchy and Anti-Hierarchy in Real and Scale Free networks." PRL 92:178702 (2004) S. Semsey et al. ``Genetic Regulation of Fluxes: Iron Homeostasis of Escherichia coli". (2006) q-bio.MN/0609042

  19. Expanding Kenya's protected areas under the Convention on Biological Diversity to maximize coverage of plant diversity.

    Science.gov (United States)

    Scherer, Laura; Curran, Michael; Alvarez, Miguel

    2017-04-01

    Biodiversity is highly valuable and critically threatened by anthropogenic degradation of the natural environment. In response, governments have pledged enhanced protected-area coverage, which requires scarce biological data to identify conservation priorities. To assist this effort, we mapped conservation priorities in Kenya based on maximizing alpha (species richness) and beta diversity (species turnover) of plant communities while minimizing economic costs. We used plant-cover percentages from vegetation surveys of over 2000 plots to build separate models for each type of diversity. Opportunity and management costs were based on literature data and interviews with conservation organizations. Species richness was predicted to be highest in a belt from Lake Turkana through Mount Kenya and in a belt parallel to the coast, and species turnover was predicted to be highest in western Kenya and along the coast. Our results suggest the expanding reserve network should focus on the coast and northeastern provinces of Kenya, where new biological surveys would also fill biological data gaps. Meeting the Convention on Biological Diversity target of 17% terrestrial coverage by 2020 would increase representation of Kenya's plant communities by 75%. However, this would require about 50 times more funds than Kenya has received thus far from the Global Environment Facility. © 2016 Society for Conservation Biology.

  20. An expanded evaluation of protein function prediction methods shows an improvement in accuracy.

    Science.gov (United States)

    Jiang, Yuxiang; Oron, Tal Ronnen; Clark, Wyatt T; Bankapur, Asma R; D'Andrea, Daniel; Lepore, Rosalba; Funk, Christopher S; Kahanda, Indika; Verspoor, Karin M; Ben-Hur, Asa; Koo, Da Chen Emily; Penfold-Brown, Duncan; Shasha, Dennis; Youngs, Noah; Bonneau, Richard; Lin, Alexandra; Sahraeian, Sayed M E; Martelli, Pier Luigi; Profiti, Giuseppe; Casadio, Rita; Cao, Renzhi; Zhong, Zhaolong; Cheng, Jianlin; Altenhoff, Adrian; Skunca, Nives; Dessimoz, Christophe; Dogan, Tunca; Hakala, Kai; Kaewphan, Suwisa; Mehryary, Farrokh; Salakoski, Tapio; Ginter, Filip; Fang, Hai; Smithers, Ben; Oates, Matt; Gough, Julian; Törönen, Petri; Koskinen, Patrik; Holm, Liisa; Chen, Ching-Tai; Hsu, Wen-Lian; Bryson, Kevin; Cozzetto, Domenico; Minneci, Federico; Jones, David T; Chapman, Samuel; Bkc, Dukka; Khan, Ishita K; Kihara, Daisuke; Ofer, Dan; Rappoport, Nadav; Stern, Amos; Cibrian-Uhalte, Elena; Denny, Paul; Foulger, Rebecca E; Hieta, Reija; Legge, Duncan; Lovering, Ruth C; Magrane, Michele; Melidoni, Anna N; Mutowo-Meullenet, Prudence; Pichler, Klemens; Shypitsyna, Aleksandra; Li, Biao; Zakeri, Pooya; ElShal, Sarah; Tranchevent, Léon-Charles; Das, Sayoni; Dawson, Natalie L; Lee, David; Lees, Jonathan G; Sillitoe, Ian; Bhat, Prajwal; Nepusz, Tamás; Romero, Alfonso E; Sasidharan, Rajkumar; Yang, Haixuan; Paccanaro, Alberto; Gillis, Jesse; Sedeño-Cortés, Adriana E; Pavlidis, Paul; Feng, Shou; Cejuela, Juan M; Goldberg, Tatyana; Hamp, Tobias; Richter, Lothar; Salamov, Asaf; Gabaldon, Toni; Marcet-Houben, Marina; Supek, Fran; Gong, Qingtian; Ning, Wei; Zhou, Yuanpeng; Tian, Weidong; Falda, Marco; Fontana, Paolo; Lavezzo, Enrico; Toppo, Stefano; Ferrari, Carlo; Giollo, Manuel; Piovesan, Damiano; Tosatto, Silvio C E; Del Pozo, Angela; Fernández, José M; Maietta, Paolo; Valencia, Alfonso; Tress, Michael L; Benso, Alfredo; Di Carlo, Stefano; Politano, Gianfranco; Savino, Alessandro; Rehman, Hafeez Ur; Re, Matteo; Mesiti, Marco; Valentini, Giorgio; Bargsten, Joachim W; van Dijk, Aalt D J; Gemovic, Branislava; Glisic, Sanja; Perovic, Vladmir; Veljkovic, Veljko; Veljkovic, Nevena; Almeida-E-Silva, Danillo C; Vencio, Ricardo Z N; Sharan, Malvika; Vogel, Jörg; Kansakar, Lakesh; Zhang, Shanshan; Vucetic, Slobodan; Wang, Zheng; Sternberg, Michael J E; Wass, Mark N; Huntley, Rachael P; Martin, Maria J; O'Donovan, Claire; Robinson, Peter N; Moreau, Yves; Tramontano, Anna; Babbitt, Patricia C; Brenner, Steven E; Linial, Michal; Orengo, Christine A; Rost, Burkhard; Greene, Casey S; Mooney, Sean D; Friedberg, Iddo; Radivojac, Predrag

    2016-09-07

    A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent.

  1. Functional quantum biology in photosynthesis and magnetoreception

    CERN Document Server

    Lambert, Neill; Cheng, Yuan-Chung; Li, Che-Ming; Chen, Guang-Yin; Nori, Franco

    2012-01-01

    Is there a functional role for quantum mechanics or coherent quantum effects in biological processes? While this question is as old as quantum theory, only recently have measurements on biological systems on ultra-fast time-scales shed light on a possible answer. In this review we give an overview of the two main candidates for biological systems which may harness such functional quantum effects: photosynthesis and magnetoreception. We discuss some of the latest evidence both for and against room temperature quantum coherence, and consider whether there is truly a functional role for coherence in these biological mechanisms. Finally, we give a brief overview of some more speculative examples of functional quantum biology including the sense of smell, long-range quantum tunneling in proteins, biological photoreceptors, and the flow of ions across a cell membrane.

  2. Integrating Functional, Developmental and Evolutionary Biology into Biology Curricula

    Science.gov (United States)

    Haave, Neil

    2012-01-01

    A complete understanding of life involves how organisms are able to function in their environment and how they arise. Understanding how organisms arise involves both their evolution and development. Thus to completely comprehend living things, biology must study their function, development and evolution. Previous proposals for standardized…

  3. Expanded function allied dental personnel and dental practice productivity and efficiency.

    Science.gov (United States)

    Beazoglou, Tryfon J; Chen, Lei; Lazar, Vickie F; Brown, L Jackson; Ray, Subhash C; Heffley, Dennis R; Berg, Rob; Bailit, Howard L

    2012-08-01

    This study examined the impact of expanded function allied dental personnel on the productivity and efficiency of general dental practices. Detailed practice financial and clinical data were obtained from a convenience sample of 154 general dental practices in Colorado. In this state, expanded function dental assistants can provide a wide range of reversible dental services/procedures, and dental hygienists can give local anesthesia. The survey identified practices that currently use expanded function allied dental personnel and the specific services/procedures delegated. Practice productivity was measured using patient visits, gross billings, and net income. Practice efficiency was assessed using a multivariate linear program, Data Envelopment Analysis. Sixty-four percent of the practices were found to use expanded function allied dental personnel, and on average they delegated 31.4 percent of delegatable services/procedures. Practices that used expanded function allied dental personnel treated more patients and had higher gross billings and net incomes than those practices that did not; the more services they delegated, the higher was the practice's productivity and efficiency. The effective use of expanded function allied dental personnel has the potential to substantially expand the capacity of general dental practices to treat more patients and to generate higher incomes for dental practices.

  4. The diverse and expanding role of mass spectrometry in structural and molecular biology.

    Science.gov (United States)

    Lössl, Philip; van de Waterbeemd, Michiel; Heck, Albert Jr

    2016-12-15

    The emergence of proteomics has led to major technological advances in mass spectrometry (MS). These advancements not only benefitted MS-based high-throughput proteomics but also increased the impact of mass spectrometry on the field of structural and molecular biology. Here, we review how state-of-the-art MS methods, including native MS, top-down protein sequencing, cross-linking-MS, and hydrogen-deuterium exchange-MS, nowadays enable the characterization of biomolecular structures, functions, and interactions. In particular, we focus on the role of mass spectrometry in integrated structural and molecular biology investigations of biological macromolecular complexes and cellular machineries, highlighting work on CRISPR-Cas systems and eukaryotic transcription complexes. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  5. Functional diversification of Argonautes in nematodes:an expanding universe

    OpenAIRE

    Buck, Amy H; Blaxter, Mark

    2013-01-01

    In the last decade, many diverse RNAi (RNA interference) pathways have been discovered that mediate gene silencing at epigenetic, transcriptional and post-transcriptional levels. The diversity of RNAi pathways is inherently linked to the evolution of Ago (Argonaute) proteins, the central protein component of RISCs (RNA-induced silencing complexes). An increasing number of diverse Agos have been identified in different species. The functions of most of these proteins are not yet known, but the...

  6. Analysis of Nigerian dentists' opinion and consequences on expanded function dental auxiliaries.

    Science.gov (United States)

    Umanah, A U; Azodo, C

    2015-06-01

    To examine Nigerian dentists' opinion on expanded function dental auxiliaries. This cross-sectional study of Nigerian dentists attending a dental conference was conducting in 2012 using self-administered questionnaire. The data were analyzed using Statistical Package for the Social Sciences version 16.0. P opinion towards expanded duty dental auxiliaries. The mean scores on consequences, of expanded function dental auxiliaries ranked redundancy of dentist as highest. Males and non-specialist significantly reported expanded function dental auxiliaries would lead to redundancy of dentists. Practitioners working in other hospitals other than teaching hospital significantly reported that appropriate legislation are necessary before expansion of duties of the dental auxiliaries can be done. The dentists with favorable opinion significantly reported that expanded duty dental auxiliaries would not cause redundancy of dentist and the task are not too difficult for dental auxiliaries with necessary training but will increase service delivery and efficiency, increase job satisfaction, lead to dental auxiliary specialization with legislation. Data from this study revealed overall unfavorable opinion of Nigerian dentists on the expanded duty dental auxiliaries. However, those with favorable opinion were significantly supportive of expanded function dental auxiliaries. This information would serve as a useful tool for Nigerian oral healthcare policy formulators.

  7. Expanded functionality of modified whey protein dispersions after transglutaminase catalysis.

    Science.gov (United States)

    Clare, Debra A; Daubert, Christopher R

    2011-05-01

    The functionality of whey dispersions, prepared with a modified whey protein concentrate (mWPC) ingredient, was significantly altered after cross-linking with microbial transglutaminase (TGase) upon pH adjustment to 8. Test TGase-mWPC solutions, pH 8, gelled faster than control mWPC dispersions, as measured in real time; whereas, the gelling temperature of pretreated TGase-mWPC samples (37 °C, 2.5 h) increased from 67.8 to 74.8 °C with a minimal change in gel strength. Prolonged prior incubation with the enzyme (37 °C, 20 h) raised the gel strength in both control mWPC and TGase-mWPC dispersions, though these values were approximately 2.7 times lower in TGase-mWPC samples. Furthermore, the gelling temperature was raised by 9 °C after extensive polymerization. The water holding capacity was not impacted by enzymatic processing while emulsions prepared with TGase-mWPC dispersions proved very stable with no evidence of phase separation during storage at room temperature for 1 mo. Moreover, the apparent viscosity of TGase-mWPC emulsions exhibited a 10-fold increase compared to nonenzyme-treated mWPC samples. The particle size was nearly 11 μm in covalently linked TGase-mWPC test fractions compared with 8 μm in nonpolymerized mWPC dispersions. Ultimately, the functional characteristics of TGase-mWPC ingredients may be designed to deliver superior performance, especially with regard to improving heat and emulsion stability. © 2011 Institute of Food Technologists®

  8. DMPTool 2: Expanding Functionality for Better Data Management Planning

    Directory of Open Access Journals (Sweden)

    Carly Strasser

    2014-07-01

    Full Text Available Scholarly researchers today are increasingly required to engage in a range of data management planning activities to comply with institutional policies, or as a precondition for publication or grant funding. The latter is especially true in the U.S. in light of the recent White House Office of Science and Technology Policy (OSTP mandate aimed at maximizing the availability of all outputs – data as well as the publications that summarize them – resulting from federally-funded research projects. To aid researchers in creating effective data management plans (DMPs, a group of organizations – California Digital Library, DataONE, Digital Curation Centre, Smithsonian Institution, University of Illinois Urbana-Champaign, and University of Virginia Library – collaborated on the development of the DMPTool, an online application that helps researchers create data management plans. The DMPTool provides detailed guidance, links to general and institutional resources, and walks a researcher through the process of generating a comprehensive plan tailored to specific DMP requirements. The uptake of the DMPTool has been positive: to date, it has been used by over 6,000 researchers from 800 institutions, making use of more than 20 requirements templates customized for funding bodies. With support from the Alfred P. Sloan Foundation, project partners are now engaged in enhancing the features of the DMPTool. The second version of the tool has enhanced functionality for plan creators and institutional administrators, as well as a redesigned user interface and an open RESTful application programming interface (API. New administrative functions provide the means for institutions to better support local research activities. New capabilities include support for plan co-ownership; workflow provisions for internal plan review; simplified maintenance and addition of DMP requirements templates; extensive capabilities for the customization of guidance and resources

  9. Metacognition: computation, biology and function.

    Science.gov (United States)

    Fleming, Stephen M; Dolan, Raymond J; Frith, Christopher D

    2012-05-19

    Many complex systems maintain a self-referential check and balance. In animals, such reflective monitoring and control processes have been grouped under the rubric of metacognition. In this introductory article to a Theme Issue on metacognition, we review recent and rapidly progressing developments from neuroscience, cognitive psychology, computer science and philosophy of mind. While each of these areas is represented in detail by individual contributions to the volume, we take this opportunity to draw links between disciplines, and highlight areas where further integration is needed. Specifically, we cover the definition, measurement, neurobiology and possible functions of metacognition, and assess the relationship between metacognition and consciousness. We propose a framework in which level of representation, order of behaviour and access consciousness are orthogonal dimensions of the conceptual landscape.

  10. [New methods and technologies expandable to the laser detection of biological and medical samples].

    Science.gov (United States)

    Shi, Gui-zhen; Du, Hai; Ge, Liao-hai; Tian, Yu; Huang, Mao-cheng; Wang, Wen-yun

    2011-07-01

    The multicolour three-photon resonant photoionization spectra and high-time-resolved laser spectrum of UI were measured with a setup composed of a Nd:YAG-laser (532 nm, operated at 10 Hz)-pumped pulsed tunable dye laser system, a time-of-flight mass spectrometer, including micro-channel plate components, ns-oscilloscope, boxcar integrator, and so on. Creative inventions of this paper are for the first time by laser-induced quantum population of the graphic method, the causes for single-colour and two-colour three-photon resonant photoionization spectra peak were given in the three-colour three-photon resonant photoionization experiment; The question how to avoid producing single-colour and two-colour three-photon resonant photoionization spectra peak was solved, That is, how to solve the problem to avoid "false peaks", so that multicolour three-photon resonant photoionization purity was raised remarkably; On this basis, not only in close proximity to energy level position with just a difference 0.642 cm, the isotopes A and B of uranium, which are difficult to distinguish, were well resolved, but the two excited state lifetime values were obtained respectively. This technology is not limited to uranium spectrum, but more importantly, it's versatile. The new methods and technologies of basic research can be expanded to samples of biological and medical research fields with laser detecting and analysis.

  11. ADF/cofilin: a functional node in cell biology.

    Science.gov (United States)

    Bernstein, Barbara W; Bamburg, James R

    2010-04-01

    Recent findings have significantly expanded our understanding of the regulation of actin-depolymerizing factor (ADF)/cofilin proteins and the profound multifaceted impact that these well-established regulators of actin dynamics have on cell biology. In this review we discuss new aspects of previously documented regulation, such as phosphorylation, but also cover novel recently established modes of regulation and functions of ADF (also known as destrin)/cofilin. We now understand that their activity responds to a vast array of inputs far greater than previously appreciated and that these proteins not only feed back to the crucially important dynamics of actin, but also to apoptosis cascades, phospholipid metabolism, and gene expression. We argue that this ability to respond to physiological changes by modulating those same changes makes the ADF/cofilin protein family a homeostatic regulator or 'functional node' in cell biology. Copyright 2010 Elsevier Ltd. All rights reserved.

  12. Functional biology of sympatric krill species

    DEFF Research Database (Denmark)

    Agersted, Mette Dalgaard; Nielsen, Torkel Gissel

    2016-01-01

    Here we compare the functional biology of the sympatric krill species, Meganyctiphanes norvegica and Thysanoessa inermis. For M. norvegica, we investigated functional responses on diatoms and copepods, together with prey size spectra on plankton ,400 mm and copepods in the size range 500–3220 mm...

  13. Expanding the landscape of chromatin modification (CM-related functional domains and genes in human.

    Directory of Open Access Journals (Sweden)

    Shuye Pu

    2010-11-01

    Full Text Available Chromatin modification (CM plays a key role in regulating transcription, DNA replication, repair and recombination. However, our knowledge of these processes in humans remains very limited. Here we use computational approaches to study proteins and functional domains involved in CM in humans. We analyze the abundance and the pair-wise domain-domain co-occurrences of 25 well-documented CM domains in 5 model organisms: yeast, worm, fly, mouse and human. Results show that domains involved in histone methylation, DNA methylation, and histone variants are remarkably expanded in metazoan, reflecting the increased demand for cell type-specific gene regulation. We find that CM domains tend to co-occur with a limited number of partner domains and are hence not promiscuous. This property is exploited to identify 47 potentially novel CM domains, including 24 DNA-binding domains, whose role in CM has received little attention so far. Lastly, we use a consensus Machine Learning approach to predict 379 novel CM genes (coding for 329 proteins in humans based on domain compositions. Several of these predictions are supported by very recent experimental studies and others are slated for experimental verification. Identification of novel CM genes and domains in humans will aid our understanding of fundamental epigenetic processes that are important for stem cell differentiation and cancer biology. Information on all the candidate CM domains and genes reported here is publicly available.

  14. Biological cluster evaluation for gene function prediction.

    Science.gov (United States)

    Klie, Sebastian; Nikoloski, Zoran; Selbig, Joachim

    2014-06-01

    Recent advances in high-throughput omics techniques render it possible to decode the function of genes by using the "guilt-by-association" principle on biologically meaningful clusters of gene expression data. However, the existing frameworks for biological evaluation of gene clusters are hindered by two bottleneck issues: (1) the choice for the number of clusters, and (2) the external measures which do not take in consideration the structure of the analyzed data and the ontology of the existing biological knowledge. Here, we address the identified bottlenecks by developing a novel framework that allows not only for biological evaluation of gene expression clusters based on existing structured knowledge, but also for prediction of putative gene functions. The proposed framework facilitates propagation of statistical significance at each of the following steps: (1) estimating the number of clusters, (2) evaluating the clusters in terms of novel external structural measures, (3) selecting an optimal clustering algorithm, and (4) predicting gene functions. The framework also includes a method for evaluation of gene clusters based on the structure of the employed ontology. Moreover, our method for obtaining a probabilistic range for the number of clusters is demonstrated valid on synthetic data and available gene expression profiles from Saccharomyces cerevisiae. Finally, we propose a network-based approach for gene function prediction which relies on the clustering of optimal score and the employed ontology. Our approach effectively predicts gene function on the Saccharomyces cerevisiae data set and is also employed to obtain putative gene functions for an Arabidopsis thaliana data set.

  15. Functional biology of sympatric krill species

    DEFF Research Database (Denmark)

    Agersted, Mette Dalgaard; Nielsen, Torkel Gissel

    2016-01-01

    Here we compare the functional biology of the sympatric krill species, Meganyctiphanes norvegica and Thysanoessa inermis. For M. norvegica, we investigated functional responses on diatoms and copepods, together with prey size spectra on plankton ,400 mm and copepods in the size range 500–3220 mm...... feed on cells .10 mm. Meganyctiphanes norvegica show maximum predation on 800–1600 mm sized copepods, corresponding to a predator:prey size ratio of 17.0+2.2. Functional response experiments with M. norvegica follow a Holling type III functional response, both when feeding on diatoms and copepods...

  16. Explaining Biological Functionality: Is Control Theory Enough ...

    African Journals Online (AJOL)

    It is generally agreed that organisms are Complex Adaptive Systems. Since the rise of Cybernetics in the middle of the last century ideas from information theory and control theory have been applied to the adaptations of biological organisms in order to explain how they work. This does not, however, explain functionality, ...

  17. Imaging cellular and molecular biological functions

    Energy Technology Data Exchange (ETDEWEB)

    Shorte, S.L. [Institut Pasteur, 75 - Paris (France). Plateforme d' Imagerie Dynamique PFID-Imagopole; Frischknecht, F. (eds.) [Heidelberg Univ. Medical School (Germany). Dept. of Parasitology

    2007-07-01

    'Imaging cellular and molecular biological function' provides a unique selection of essays by leading experts, aiming at scientist and student alike who are interested in all aspects of modern imaging, from its application and up-scaling to its development. Indeed the philosophy of this volume is to provide student, researcher, PI, professional or provost the means to enter this applications field with confidence, and to construct the means to answer their own specific questions. (orig.)

  18. Aegerolysins: structure, function, and putative biological role.

    Science.gov (United States)

    Berne, Sabina; Lah, Ljerka; Sepcić, Kristina

    2009-04-01

    Aegerolysins, discovered in fungi, bacteria and plants, are highly similar proteins with interesting biological properties. Certain aegerolysins possess antitumoral, antiproliferative, and antibacterial activities. Further possible medicinal applications include their use in the prevention of atherosclerosis, or as vaccines. Additional biotechnological value of fungal aegerolysins lies in their involvement in development, which could improve cultivation of commercially important edible mushrooms. Besides, new insights on microheterogeneity of raft-like membrane domains could be gained by using aegerolysins as specific markers in cell and molecular biology. Although the exact function of aegerolysins in their producing organisms remains to be explained, they are biochemically well characterized all-beta structured proteins sharing the following common features: low isoelectric points, similar molecular weights (15-17 kDa), and stability in a wide pH range.

  19. Marine Carotenoids: Biological Functions and Commercial Applications

    Directory of Open Access Journals (Sweden)

    José M. Vega

    2011-03-01

    Full Text Available Carotenoids are the most common pigments in nature and are synthesized by all photosynthetic organisms and fungi. Carotenoids are considered key molecules for life. Light capture, photosynthesis photoprotection, excess light dissipation and quenching of singlet oxygen are among key biological functions of carotenoids relevant for life on earth. Biological properties of carotenoids allow for a wide range of commercial applications. Indeed, recent interest in the carotenoids has been mainly for their nutraceutical properties. A large number of scientific studies have confirmed the benefits of carotenoids to health and their use for this purpose is growing rapidly. In addition, carotenoids have traditionally been used in food and animal feed for their color properties. Carotenoids are also known to improve consumer perception of quality; an example is the addition of carotenoids to fish feed to impart color to farmed salmon.

  20. Neurotrophin Propeptides: Biological Functions and Molecular Mechanisms.

    Science.gov (United States)

    Rafieva, Lola M; Gasanov, Eugene V

    2016-01-01

    Neurotrophins constitute a family of growth factors that play a key role in the regulation of the development and function of the central and peripheral nervous systems. A common feature of all the neurotrophins is their synthesis in cells as long precursors (pre-pro-neurotrophins) that contain an N-terminal signal peptide, a following propeptide and the mature neurotrophin. Although the signal peptide functions have been well studied, the role of neurotrophin propeptides is not so clear. Here, we briefly summarize the biochemistry of neurotrophin propeptides, including their role as folding-assistants for the mature factor and their role in processing and in secretion of neurotrophins. In the main part of the review we summarize our current state of knowledge of the biological activity of neurotrophin propeptides, their possible mechanisms of action, and their potential influence on the activity of the mature neurotrophins.

  1. Leveraging a Relationship with Biology to Expand a Relationship with Physics

    CERN Document Server

    Sawtelle, Vashti

    2014-01-01

    This work examines how experiences in one disciplinary domain (biology) can impact the relationship a student builds with another domain (physics). We present a model for disciplinary relationships using the constructs of identity, affect, and epistemology. With these constructs we examine an ethnographic case study of a student who experienced a significant shift in her relationship with physics. We describe how this shift demonstrates (1) a stronger identification with physics, (2) a more mixed affective stance towards physics, and (3) more expert-like ways of knowing in physics. We argue that recruiting the students relationship with biology into experiences of learning physics impacted her relationship with physics as well as her sense of how physics and biology are linked.

  2. Diffusion in an expanding medium: Fokker-Planck equation, Green's function, and first-passage properties.

    Science.gov (United States)

    Yuste, S B; Abad, E; Escudero, C

    2016-09-01

    We present a classical, mesoscopic derivation of the Fokker-Planck equation for diffusion in an expanding medium. To this end, we take a conveniently generalized Chapman-Kolmogorov equation as the starting point. We obtain an analytical expression for the Green's function (propagator) and investigate both analytically and numerically how this function and the associated moments behave. We also study first-passage properties in expanding hyperspherical geometries. We show that in all cases the behavior is determined to a great extent by the so-called Brownian conformal time τ(t), which we define via the relation τ[over ̇]=1/a^{2}, where a(t) is the expansion scale factor. If the medium expansion is driven by a power law [a(t)∝t^{γ} with γ>0], then we find interesting crossover effects in the mixing effectiveness of the diffusion process when the characteristic exponent γ is varied. Crossover effects are also found at the level of the survival probability and of the moments of the first passage-time distribution with two different regimes separated by the critical value γ=1/2. The case of an exponential scale factor is analyzed separately both for expanding and contracting media. In the latter situation, a stationary probability distribution arises in the long-time limit.

  3. Biological pathways and genetic mechanisms involved in social functioning

    NARCIS (Netherlands)

    Ordoñana, Juan R.; Bartels, Meike; Boomsma, Dorret I.; Cella, David; Mosing, Miriam; Oliveira, Joao R.; Patrick, Donald L.; Veenhoven, Ruut; Wagner, Gert G.; Sprangers, Mirjam A. G.; Abernethy, Amy P.; Baas, Frank; Barsevick, Andrea M.; Bottomley, Andrew; Brundage, Michael; Chauhan, Cynthia; Cleeland, Charles S.; Coens, Corneel; Dueck, Amylou C.; Frost, Marlene H.; Hall, Per; Halyard, Michele Y.; Klepstad, Pål; Martin, Nicholas G.; Miaskowski, Christine; Movsas, Benjamin; van Noorden, Cornelis J. F.; Oliveira, Joao Ricardo; Ordoñana, Juan; Pedersen, Nancy L.; Raat, Hein; Reeve, Bryce; Ropka, Mary E.; Shi, Quiling; Shinozaki, Gen; Singh, Jasvinder A.; Sloan, Jeff A.; Swaab, Dick; Talwalker, Jayant; Yang, Ping; Zwinderman, Ailko H.

    2013-01-01

    To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants that

  4. Biological pathways and genetic mechanisms involved in social functioning

    NARCIS (Netherlands)

    Ordonana, J.R.; Bartels, M.; Boomsma, D.I.; Cella, D.; Mosing, M.; Oliveira, J.R.; Patrick, D.L.; Veenhoven, R.; Wagner, G.G.; Sprangers, M.A.G.

    2013-01-01

    Purpose: To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants

  5. Leveraging a Relationship with Biology to Expand a Relationship with Physics

    Science.gov (United States)

    Sawtelle, Vashti; Turpen, Chandra

    2016-01-01

    This work examines how experiences in one disciplinary domain (biology) can impact the relationship a student builds with another domain (physics). We present a model for disciplinary relationships using the constructs of identity, affect, and epistemology. With these constructs we examine an ethnographic case study of a student who experienced a…

  6. geneLAB: Expanding the Impact of NASA's Biological Research in Space

    Science.gov (United States)

    Rayl, Nicole; Smith, Jeffrey D.

    2014-01-01

    The geneLAB project is designed to leverage the value of large 'omics' datasets from molecular biology projects conducted on the ISS by making these datasets available, citable, discoverable, interpretable, reusable, and reproducible. geneLAB will create a collaboration space with an integrated set of tools for depositing, accessing, analyzing, and modeling these diverse datasets from spaceflight and related terrestrial studies.

  7. Adipose Tissue Function and Expandability as Determinants of Lipotoxicity and the Metabolic Syndrome.

    Science.gov (United States)

    Carobbio, Stefania; Pellegrinelli, Vanessa; Vidal-Puig, Antonio

    2017-01-01

    The adipose tissue organ is organised as distinct anatomical depots located all along the body axis and it is constituted of three different types of adipocytes : white, beige and brown which are integrated with vascular, immune, neural and extracellular stroma cells. These distinct adipocytes serve different specialised functions. The main function of white adipocytes is to ensure healthy storage of excess nutrients/energy and its rapid mobilisation to supply the demand of energy imposed by physiological cues in other organs, whereas brown and beige adipocytes are designed for heat production through uncoupling lipid oxidation from energy production. The concert action of the three type of adipocytes/tissues has been reported to ensure an optimal metabolic status in rodents. However, when one or multiple of these adipose depots become dysfunctional as a consequence of sustained lipid/nutrient overload, then insulin resistance and associated metabolic complications ensue. These metabolic alterations negatively affects the adipose tissue functionality and compromises global metabolic homeostasis. Optimising white adipose tissue expandability and its functional metabolic flexibility and/or promoting brown/beige mediated thermogenic activity counteracts obesity and its associated lipotoxic metabolic effects. The development of these therapeutic approaches requires a deep understanding of adipose tissue in all broad aspects. In this chapter we will discuss the characteristics of the different adipose tissue depots with respect to origins and precursors recruitment, plasticity, cellular composition and expandability capacity as well as molecular and metabolic signatures in both physiological and pathophysiological conditions.

  8. Design of the Nonlinear Pin Rubber Forming Equipment Integrating the Functions of Extruding, Dewatering, Drying & Expanding

    Directory of Open Access Journals (Sweden)

    Yuefeng Yuan

    2014-12-01

    Full Text Available The top priority of car-tire suppliers is to improve wetland grip force of the using tires, reduce the rolling resistance and the rolling noise of tires. It is urgent for the tire industry to research and develop high-performance tires to solve the above problems. They must use the high- performance synthetic rubber and auxiliary rubber to develop the most advanced manufacturing technologies and equipment. Silica, a kind of important tire auxiliary rubber, can significantly reduce the rolling resistance of tires, improve the grip force and properties resistant to ice, wetness or slippery of tires. In this paper, based on the conventional tire rubber forming technologies of extrusion, dewatering, drying and expanding, a study is made on the conical screw, the dewatering barrel, the drying barrel, the pin layout scheme, the expanding die head, cutter and the control system. The nonlinear pin rubber forming equipment integrating the functions of extrusion, dewatering, drying and expanding is designed and applied to tire auxiliary rubber forming. The experiment shows that the forming device can realize the one-step forming, with high forming efficiency, low cost and less labor.

  9. Recent advances of molecular toolbox construction expand Pichia pastoris in synthetic biology applications.

    Science.gov (United States)

    Kang, Zhen; Huang, Hao; Zhang, Yunfeng; Du, Guocheng; Chen, Jian

    2017-01-01

    Pichia pastoris: (reclassified as Komagataella phaffii), a methylotrophic yeast strain has been widely used for heterologous protein production because of its unique advantages, such as readily achievable high-density fermentation, tractable genetic modifications and typical eukaryotic post-translational modifications. More recently, P. pastoris as a metabolic pathway engineering platform has also gained much attention. In this mini-review, we addressed recent advances of molecular toolboxes, including synthetic promoters, signal peptides, and genome engineering tools that established for P. pastoris. Furthermore, the applications of P. pastoris towards synthetic biology were also discussed and prospected especially in the context of genome-scale metabolic pathway analysis.

  10. Synthetic biology with artificially expanded genetic information systems. From personalized medicine to extraterrestrial life.

    Science.gov (United States)

    Benner, Steven A; Hutter, Daniel; Sismour, A Michael

    2003-01-01

    Over 15 years ago, the Benner group noticed that the DNA alphabet need not be limited to the four standard nucleotides known in natural DNA. Rather, twelve nucleobases forming six base pairs joined by mutually exclusive hydrogen bonding patterns are possible within the geometry of the Watson-Crick pair (Fig. 1). Synthesis and studies on these compounds have brought us to the threshold of a synthetic biology, an artificial chemical system that does basic processes needed for life (in particular, Darwinian evolution), but with unnatural chemical structures. At the same time, the artificial genetic information systems (AEGIS) that we have developed have been used in FDA-approved commercial tests for managing HIV and hepatitis C infections in individual patients, and in a tool that seeks the virus for severe acute respiratory syndrome (SARS). AEGIS also supports the next generation of robotic probes to search for genetic molecules on Mars, Europa, and elsewhere where NASA probes will travel.

  11. Economic impact of expanded use of biologic therapy for the treatment of rheumatoid arthritis and Crohn's disease in Argentina, Brazil, Colombia, and Mexico.

    Science.gov (United States)

    Tundia, Namita; Kotze, Paulo Gustavo; Rojas Serrano, Jorge; Mendes de Abreu, Mirhelen; Skup, Martha; Macaulay, Dendy; Signorovitch, James; Chaves, Leonardo; Chao, Jingdong; Bao, Yanjun

    2016-12-01

    To estimate economic impact resulting from increased biologics use for treatment of rheumatoid arthritis (RA) and Crohn's disease (CD) in Argentina, Brazil, Colombia, and Mexico. The influence of increasing biologics use for treatment of RA during 2012-2022 and for treatment of CD during 2013-2023 was modeled from a societal perspective. The economic model incorporated current and projected medical, indirect, and drug costs and epidemiologic and economic factors. Costs associated with expanded biologics use for RA were compared with non-expanded use in Argentina, Brazil, Colombia, and Mexico. A similar analysis was conducted for CD in Brazil, Colombia, and Mexico. Accounting for additional costs of biologics and medical and indirect cost offsets, the model predicts that expanded use of biologics for patients with RA from 2012 to 2022 will result in cumulative net cost savings of ARS$2.351 billion in Argentina, R$9.004 billion in Brazil, COP$728.577 billion in Colombia, and MXN$18.02 billion in Mexico; expanded use of biologics for patients with CD from 2013 to 2023 will result in cumulative net cost savings for patients with CD of R$0.082 billion in Brazil, COP$502.74 billion in Colombia, and MXN$1.80 billion in Mexico. Indirect cost offsets associated with expanded biologics use were a key driver in reducing annual per-patient net costs for RA and CD. Future economic projections are limited by the potential variance between projected and actual future values of biologic prices, wages, medical costs, and gross national product for each country. Increasing biologics use to treat RA and CD may limit cost growth over time by reducing medical and indirect costs. These findings may inform policy decisions regarding biologics use in Argentina, Brazil, Colombia, and Mexico.

  12. Structure and biological functions of fungal cerebrosides

    Directory of Open Access Journals (Sweden)

    Barreto-Bergter Eliana

    2004-01-01

    Full Text Available Ceramide monohexosides (CMHs, cerebrosides are glycosphingolipids composed of a hydrophobic ceramide linked to one sugar unit. In fungal cells, CMHs are very conserved molecules consisting of a ceramide moiety containing 9-methyl-4,8-sphingadienine in amidic linkage to 2-hydroxyoctadecanoic or 2-hydroxyhexadecanoic acids, and a carbohydrate portion consisting of one residue of glucose or galactose. 9-Methyl 4,8-sphingadienine-containing ceramides are usually glycosylated to form fungal cerebrosides, but the recent description of a ceramide dihexoside (CDH presenting phytosphingosine in Magnaporthe grisea suggests the existence of alternative pathways of ceramide glycosylation in fungal cells. Along with their unique structural characteristics, fungal CMHs have a peculiar subcellular distribution and striking biological properties. In Pseudallescheria boydii, Candida albicans, Cryptococcus neoformans, Aspergillus nidulans, A. fumigatus, and Schizophyllum commune, CMHs are apparently involved in morphological transitions and fungal growth. The elucidation of structural and functional aspects of fungal cerebrosides may therefore contribute to the design of new antifungal agents inhibiting growth and differentiation of pathogenic species.

  13. Vertical expandable prosthetic titanium rib device insertion: does it improve pulmonary function?

    Science.gov (United States)

    Gadepalli, Samir K; Hirschl, Ronald B; Tsai, Wan C; Caird, Michelle S; Vanderhave, Kelly L; Strouse, Peter J; Drongowski, Robert A; Farley, Frances A

    2011-01-01

    Vertical expandable prosthetic titanium rib (VEPTR) insertion and expansion has been advocated to increase thoracic volume and pulmonary function in patients with thoracic insufficiency syndrome. We reviewed our experience with VEPTR implantation to determine if lung function and growth is augmented, to determine the children's functional status, and if the scoliosis is controlled. From 2006 to 2010, 29 insertions and 57 expansions were performed in 26 patients at our institution. Demographic data were reviewed in conjunction with complications, scoliosis angles, pulmonary function tests (PFTs), and computed tomography-guided 3D reconstructions to determine lung volumes; and quality of life scores were determined using a modified Scoliosis Research Society (SRS) questionnaire preoperatively and postoperatively. The groups were also stratified by age (because of lung growth potential), disease (congenital or infantile scoliosis, Jeune syndrome, neuromuscular, other structural thoracic disorders), and sex. Analyses using SPSS (SPSS, Chicago, Ill) were performed with P VEPTR placement. Pulmonary function, lung volume, and patient subjective assessments did not increase dramatically after VEPTR placement, although scoliosis angles improved. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Active Interaction Mapping as a tool to elucidate hierarchical functions of biological processes.

    Science.gov (United States)

    Farré, Jean-Claude; Kramer, Michael; Ideker, Trey; Subramani, Suresh

    2017-07-03

    Increasingly, various 'omics data are contributing significantly to our understanding of novel biological processes, but it has not been possible to iteratively elucidate hierarchical functions in complex phenomena. We describe a general systems biology approach called Active Interaction Mapping (AI-MAP), which elucidates the hierarchy of functions for any biological process. Existing and new 'omics data sets can be iteratively added to create and improve hierarchical models which enhance our understanding of particular biological processes. The best datatypes to further improve an AI-MAP model are predicted computationally. We applied this approach to our understanding of general and selective autophagy, which are conserved in most eukaryotes, setting the stage for the broader application to other cellular processes of interest. In the particular application to autophagy-related processes, we uncovered and validated new autophagy and autophagy-related processes, expanded known autophagy processes with new components, integrated known non-autophagic processes with autophagy and predict other unexplored connections.

  15. Function and regulation of lipid biology in Caenorhabditis elegans aging

    Directory of Open Access Journals (Sweden)

    Nicole Shangming Hou

    2012-05-01

    Full Text Available Rapidly expanding aging populations and a concomitant increase in the prevalence of age-related diseases are global health problems today. Over the past three decades, a large body of work has led to the identification of genes and regulatory networks that affect longevity and health span, often benefitting from the tremendous power of genetics in vertebrate and invertebrate model organisms. Interestingly, many of these factors appear linked to lipids, important molecules that participate in cellular signaling, energy metabolism, and structural compartmentalization. Despite the putative link between lipids and longevity, the role of lipids in aging remains poorly understood. Emerging data from the model organism Caenorhabditis elegans suggest that lipid composition may change during aging, as several pathways that influence aging also regulate lipid metabolism enzymes; moreover, some of these enzymes apparently play key roles in the pathways that affect the rate of aging. By understanding how lipid biology is regulated during C. elegans aging, and how it impacts molecular, cellular and organismal function, we may gain insight into novel ways to delay aging using genetic or pharmacological interventions. In the present review we discuss recent insights into the roles of lipids in C. elegans aging, including regulatory roles played by lipids themselves, the regulation of lipid metabolic enzymes, and the roles of lipid metabolism genes in the pathways that affect aging.

  16. Marine Carotenoids: Biological Functions and Commercial Applications

    NARCIS (Netherlands)

    Vilchez, C.; Forján, E.; Cuaresma, M.; Bédmar, F.; Garbayo, I.; Vega, J.M.

    2011-01-01

    Carotenoids are the most common pigments in nature and are synthesized by all photosynthetic organisms and fungi. Carotenoids are considered key molecules for life. Light capture, photosynthesis photoprotection, excess light dissipation and quenching of singlet oxygen are among key biological

  17. Functional Analysis of Serially Expanded Human iPS Cell-Derived RPE Cultures

    Science.gov (United States)

    Singh, Ruchira; Phillips, M. Joseph; Kuai, David; Meyer, Jackelyn; Martin, Jessica M.; Smith, Molly A.; Perez, Enio T.; Shen, Wei; Wallace, Kyle A.; Capowski, Elizabeth E.; Wright, Lynda S.; Gamm, David M.

    2013-01-01

    Purpose. To determine the effects of serial expansion on the cellular, molecular, and functional properties of human iPS cell (hiPSC)-derived RPE cultures. Methods. Fibroblasts obtained from four individuals were reprogrammed into hiPSCs and differentiated to RPE cells using previously described methods. Patches of deeply pigmented hiPSC-RPE were dissected, dissociated, and grown in culture until they re-formed pigmented monolayers. Subsequent passages were obtained by repeated dissociation, expansion, and maturation of RPE into pigmented monolayers. Gene and protein expression profiles and morphological and functional characteristics of hiPSC-RPE at different passages were compared with each other and to human fetal RPE (hfRPE). Results. RPE from all four hiPSC lines could be expanded more than 1000-fold when serially passaged as pigmented monolayer cultures. Importantly, expansion of hiPSC-RPE monolayers over the first three passages (P1–P3) resulted in decreased expression of pluripotency and neuroretinal markers and maintenance of characteristic morphological features and gene and protein expression profiles. Furthermore, P1 to P3 hiPSC-RPE monolayers reliably demonstrated functional tight junctions, G-protein–coupled receptor-mediated calcium transients, phagocytosis and degradation of photoreceptor outer segments, and polarized secretion of biomolecules. In contrast, P4 hiPSC-RPE cells failed to form monolayers and possessed altered morphological and functional characteristics and gene expression levels. Conclusions. Highly differentiated, pigmented hiPSC-RPE monolayers can undergo limited serial expansion while retaining key cytological and functional attributes. However, passaging hiPSC-RPE cultures beyond senescence leads to loss of such features. Our findings support limited, controlled passaging of patient-specific hiPSC-RPE to procure cells needed for in vitro disease modeling, drug screening, and cellular transplantation. PMID:24030465

  18. Investigation of the proteolytic functions of an expanded cercarial elastase gene family in Schistosoma mansoni.

    Directory of Open Access Journals (Sweden)

    Jessica R Ingram

    Full Text Available Cercarial elastase is the major invasive larval protease in Schistosoma mansoni, a parasitic blood fluke, and is essential for host skin invasion. Genome sequence analysis reveals a greatly expanded family of cercarial elastase gene isoforms in Schistosoma mansoni. This expansion appears to be unique to S. mansoni, and it is unknown whether gene duplication has led to divergent protease function.Profiling of transcript and protein expression patterns reveals that cercarial elastase isoforms are similarly expressed throughout the S. mansoni life cycle. Computational modeling predicts key differences in the substrate-binding pockets of various cercarial elastase isoforms, suggesting a diversification of substrate preferences compared with the ancestral gene of the family. In addition, active site labeling of SmCE reveals that it is activated prior to exit of the parasite from its intermediate snail host.The expansion of the cercarial gene family in S. mansoni is likely to be an example of gene dosage. In addition to its critical role in human skin penetration, data presented here suggests a novel role for the protease in egress from the intermediate snail host. This study demonstrates how enzyme activity-based analysis complements genomic and proteomic studies, and is key in elucidating proteolytic function.

  19. Data Transformation Functions for Expanded Search Spaces in Geographic Sample Supervised Segment Generation

    Directory of Open Access Journals (Sweden)

    Christoff Fourie

    2014-04-01

    Full Text Available Sample supervised image analysis, in particular sample supervised segment generation, shows promise as a methodological avenue applicable within Geographic Object-Based Image Analysis (GEOBIA. Segmentation is acknowledged as a constituent component within typically expansive image analysis processes. A general extension to the basic formulation of an empirical discrepancy measure directed segmentation algorithm parameter tuning approach is proposed. An expanded search landscape is defined, consisting not only of the segmentation algorithm parameters, but also of low-level, parameterized image processing functions. Such higher dimensional search landscapes potentially allow for achieving better segmentation accuracies. The proposed method is tested with a range of low-level image transformation functions and two segmentation algorithms. The general effectiveness of such an approach is demonstrated compared to a variant only optimising segmentation algorithm parameters. Further, it is shown that the resultant search landscapes obtained from combining mid- and low-level image processing parameter domains, in our problem contexts, are sufficiently complex to warrant the use of population based stochastic search methods. Interdependencies of these two parameter domains are also demonstrated, necessitating simultaneous optimization.

  20. Expanded functional diversity of shaker K(+ channels in cnidarians is driven by gene expansion.

    Directory of Open Access Journals (Sweden)

    Timothy Jegla

    Full Text Available The genome of the cnidarian Nematostella vectensis (starlet sea anemone provides a molecular genetic view into the first nervous systems, which appeared in a late common ancestor of cnidarians and bilaterians. Nematostella has a surprisingly large and diverse set of neuronal signaling genes including paralogs of most neuronal signaling molecules found in higher metazoans. Several ion channel gene families are highly expanded in the sea anemone, including three subfamilies of the Shaker K(+ channel gene family: Shaker (Kv1, Shaw (Kv3 and Shal (Kv4. In order to better understand the physiological significance of these voltage-gated K(+ channel expansions, we analyzed the function of 18 members of the 20 gene Shaker subfamily in Nematostella. Six of the Nematostella Shaker genes express functional homotetrameric K(+ channels in vitro. These include functional orthologs of bilaterian Shakers and channels with an unusually high threshold for voltage activation. We identified 11 Nematostella Shaker genes with a distinct "silent" or "regulatory" phenotype; these encode subunits that function only in heteromeric channels and serve to further diversify Nematostella Shaker channel gating properties. Subunits with the regulatory phenotype have not previously been found in the Shaker subfamily, but have evolved independently in the Shab (Kv2 family in vertebrates and the Shal family in a cnidarian. Phylogenetic analysis indicates that regulatory subunits were present in ancestral cnidarians, but have continued to diversity at a high rate after the split between anthozoans and hydrozoans. Comparison of Shaker family gene complements from diverse metazoan species reveals frequent, large scale duplication has produced highly unique sets of Shaker channels in the major metazoan lineages.

  1. Expanded functional diversity of shaker K(+) channels in cnidarians is driven by gene expansion.

    Science.gov (United States)

    Jegla, Timothy; Marlow, Heather Q; Chen, Bihan; Simmons, David K; Jacobo, Sarah M; Martindale, Mark Q

    2012-01-01

    The genome of the cnidarian Nematostella vectensis (starlet sea anemone) provides a molecular genetic view into the first nervous systems, which appeared in a late common ancestor of cnidarians and bilaterians. Nematostella has a surprisingly large and diverse set of neuronal signaling genes including paralogs of most neuronal signaling molecules found in higher metazoans. Several ion channel gene families are highly expanded in the sea anemone, including three subfamilies of the Shaker K(+) channel gene family: Shaker (Kv1), Shaw (Kv3) and Shal (Kv4). In order to better understand the physiological significance of these voltage-gated K(+) channel expansions, we analyzed the function of 18 members of the 20 gene Shaker subfamily in Nematostella. Six of the Nematostella Shaker genes express functional homotetrameric K(+) channels in vitro. These include functional orthologs of bilaterian Shakers and channels with an unusually high threshold for voltage activation. We identified 11 Nematostella Shaker genes with a distinct "silent" or "regulatory" phenotype; these encode subunits that function only in heteromeric channels and serve to further diversify Nematostella Shaker channel gating properties. Subunits with the regulatory phenotype have not previously been found in the Shaker subfamily, but have evolved independently in the Shab (Kv2) family in vertebrates and the Shal family in a cnidarian. Phylogenetic analysis indicates that regulatory subunits were present in ancestral cnidarians, but have continued to diversity at a high rate after the split between anthozoans and hydrozoans. Comparison of Shaker family gene complements from diverse metazoan species reveals frequent, large scale duplication has produced highly unique sets of Shaker channels in the major metazoan lineages.

  2. Expanding comparative-advantage biological market models: contingency of mutualism on partners' resource requirements and acquisition trade-offs.

    Science.gov (United States)

    Hoeksema, Jason D; Schwartz, Mark W

    2003-05-07

    We expand the comparative-advantage biological market-modelling framework to show how differences between partners, both in their abilities to acquire two resources and in their requirements for those resources, can affect the net benefit of participating in interspecific resource exchange. In addition, the benefits derived from resource trading depend strongly on the nature of the trade-off between the acquisition of one resource and the acquisition of another, described here by the shape (linear, convex or concave) of the resource acquisition constraints of the individuals involved. Combined with previous results, these analyses provide a suite of predictions about whether or not resource exchange is beneficial for two heterospecific individuals relative to a strategy of non-interaction. The benefit derived from resource exchange depends on three factors: (i) relative differences between the partners in their resource acquisition abilities; (ii) relative differences between the partners in their resource requirements; and (iii) variation in the shape of resource acquisition trade-offs. We find that such an explicit consideration of resource requirements and acquisition abilities can provide useful and sometimes non-intuitive predictions about the benefits of resource exchange, and also which resources should be traded by which species.

  3. A functional overview of conservation biological control

    DEFF Research Database (Denmark)

    Begg, Graham S; Cook, Samantha M; Dye, Richard

    2017-01-01

    Conservation biological control (CBC) is a sustainable approach to pest management that can contribute to a reduction in pesticide use as part of an Integrated Pest Management (IPM) strategy. CBC is based on the premise that countering habitat loss and environmental disturbance associated...

  4. Structure-based function prediction of the expanding mollusk tyrosinase family

    Science.gov (United States)

    Huang, Ronglian; Li, Li; Zhang, Guofan

    2017-01-01

    Tyrosinase (Ty) is a common enzyme found in many different animal groups. In our previous study, genome sequencing revealed that the Ty family is expanded in the Pacific oyster (Crassostrea gigas). Here, we examine the larger number of Ty family members in the Pacific oyster by high-level structure prediction to obtain more information about their function and evolution, especially the unknown role in biomineralization. We verified 12 Ty gene sequences from Crassostrea gigas genome and Pinctada fucata martensii transcriptome. By using phylogenetic analysis of these Tys with functionally known Tys from other molluscan species, eight subgroups were identified (CgTy_s1, CgTy_s2, MolTy_s1, MolTy-s2, MolTy-s3, PinTy-s1, PinTy-s2 and PviTy). Structural data and surface pockets of the dinuclear copper center in the eight subgroups of molluscan Ty were obtained using the latest versions of prediction online servers. Structural comparison with other Ty proteins from the protein databank revealed functionally important residues (HA1, HA2, HA3, HB1, HB2, HB3, Z1-Z9) and their location within these protein structures. The structural and chemical features of these pockets which may related to the substrate binding showed considerable variability among mollusks, which undoubtedly defines Ty substrate binding. Finally, we discuss the potential driving forces of Ty family evolution in mollusks. Based on these observations, we conclude that the Ty family has rapidly evolved as a consequence of substrate adaptation in mollusks.

  5. Structure-based function prediction of the expanding mollusk tyrosinase family

    Science.gov (United States)

    Huang, Ronglian; Li, Li; Zhang, Guofan

    2017-11-01

    Tyrosinase (Ty) is a common enzyme found in many different animal groups. In our previous study, genome sequencing revealed that the Ty family is expanded in the Pacific oyster ( Crassostrea gigas). Here, we examine the larger number of Ty family members in the Pacific oyster by high-level structure prediction to obtain more information about their function and evolution, especially the unknown role in biomineralization. We verified 12 Ty gene sequences from Crassostrea gigas genome and Pinctada fucata martensii transcriptome. By using phylogenetic analysis of these Tys with functionally known Tys from other molluscan species, eight subgroups were identified (CgTy_s1, CgTy_s2, MolTy_s1, MolTy-s2, MolTy-s3, PinTy-s1, PinTy-s2 and PviTy). Structural data and surface pockets of the dinuclear copper center in the eight subgroups of molluscan Ty were obtained using the latest versions of prediction online servers. Structural comparison with other Ty proteins from the protein databank revealed functionally important residues (HA1, HA2, HA3, HB1, HB2, HB3, Z1-Z9) and their location within these protein structures. The structural and chemical features of these pockets which may related to the substrate binding showed considerable variability among mollusks, which undoubtedly defines Ty substrate binding. Finally, we discuss the potential driving forces of Ty family evolution in mollusks. Based on these observations, we conclude that the Ty family has rapidly evolved as a consequence of substrate adaptation in mollusks.

  6. Functionality Evaluation of a Novel Smart Expandable Pedicle Screw to Mitigate Osteoporosis Effect in Bone Fixation: Modeling and Experimentation

    Directory of Open Access Journals (Sweden)

    Ahmadreza Eshghinejad

    2013-01-01

    Full Text Available This paper proposes a novel expandable-retractable pedicle screw and analyzes its functionality. A specially designed pedicle screw is described which has the ability to expand and retract using nitinol elements. The screw is designed to expand in body temperature and retract by cooling the screw. This expansion-retraction function is verified in an experiment designed in larger scale using a nitinol antagonistic assembly. The results of this experiment are compared to the results of a finite element model developed in Abaqus in combination with a user material subroutine (UMAT. This code has been developed to analyze the nonlinear thermomechanical behavior of shape memory alloy materials. The functionality of the proposed screw is evaluated with simulation and experimentation in a pullout test as well. The pullout force of a normal screw inserted in a normal bone was simulated, and the result is compared with the results of the expandable screw in osteoporotic bone. Lastly, strength of the designed pedicle screw in a foam block is also verified with experiment. The reported finite element simulations and experiments are the proof for the concept of nitinol expandable-retractable elements on a pedicle screw which validate the functionality in a pullout test.

  7. Expanding Diversity in Molecular Structures and Functions of the IL-6/IL-12 Heterodimeric Cytokine Family

    Directory of Open Access Journals (Sweden)

    Hideaki Hasegawa

    2016-11-01

    , promiscuity within the IL-6/IL-12 family cytokines complicates structural and functional clarification and assignment of individual cytokines. A better understanding of the recent advances and expanding diversity in molecular structures and functions of the IL-6/IL-12 family cytokines could allow the creation of novel therapeutic strategies by using them as tools and targeted molecules.

  8. New insights into epididymal biology and function

    National Research Council Canada - National Science Library

    Cornwall, Gail A

    .... This review focuses on recent progress in our understanding of epididymal function including its development, role of the luminal microenvironment in sperm maturation, regulation and novel mechanisms...

  9. Fibroblast Growth Factors: Biology, Function, and Application for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Ye-Rang Yun

    2010-01-01

    Full Text Available Fibroblast growth factors (FGFs that signal through FGF receptors (FGFRs regulate a broad spectrum of biological functions, including cellular proliferation, survival, migration, and differentiation. The FGF signal pathways are the RAS/MAP kinase pathway, PI3 kinase/AKT pathway, and PLCγ pathway, among which the RAS/MAP kinase pathway is known to be predominant. Several studies have recently implicated the in vitro biological functions of FGFs for tissue regeneration. However, to obtain optimal outcomes in vivo, it is important to enhance the half-life of FGFs and their biological stability. Future applications of FGFs are expected when the biological functions of FGFs are potentiated through the appropriate use of delivery systems and scaffolds. This review will introduce the biology and cellular functions of FGFs and deal with the biomaterials based delivery systems and their current applications for the regeneration of tissues, including skin, blood vessel, muscle, adipose, tendon/ligament, cartilage, bone, tooth, and nerve tissues.

  10. Expanding the Range of Plant Functional Diversity Represented in Global Vegetation Models: Towards Lineage-based Plant Functional Types

    Science.gov (United States)

    Still, C. J.; Griffith, D.; Edwards, E.; Forrestel, E.; Lehmann, C.; Anderson, M.; Craine, J.; Pau, S.; Osborne, C.

    2014-12-01

    Variation in plant species traits, such as photosynthetic and hydraulic properties, can indicate vulnerability or resilience to climate change, and feed back to broad-scale spatial and temporal patterns in biogeochemistry, demographics, and biogeography. Yet, predicting how vegetation will respond to future environmental changes is severely limited by the inability of our models to represent species-level trait variation in processes and properties, as current generation process-based models are mostly based on the generalized and abstracted concept of plant functional types (PFTs) which were originally developed for hydrological modeling. For example, there are close to 11,000 grass species, but most vegetation models have only a single C4 grass and one or two C3 grass PFTs. However, while species trait databases are expanding rapidly, they have been produced mostly from unstructured research, with a focus on easily researched traits that are not necessarily the most important for determining plant function. Additionally, implementing realistic species-level trait variation in models is challenging. Combining related and ecologically similar species in these models might ameliorate this limitation. Here we argue for an intermediate, lineage-based approach to PFTs, which draws upon recent advances in gene sequencing and phylogenetic modeling, and where trait complex variations and anatomical features are constrained by a shared evolutionary history. We provide an example of this approach with grass lineages that vary in photosynthetic pathway (C3 or C4) and other functional and structural traits. We use machine learning approaches and geospatial databases to infer the most important environmental controls and climate niche variation for the distribution of grass lineages, and utilize a rapidly expanding grass trait database to demonstrate examples of lineage-based grass PFTs. For example, grasses in the Andropogoneae are typically tall species that dominate wet and

  11. FUNCTION IN BIOLOGY: ETIOLOGICAL AND ORGANIZATIONAL PERSPECTIVES

    Directory of Open Access Journals (Sweden)

    Nunes Neto Nei Freitas Freitas

    2009-12-01

    -ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

    ABSTRACT. In this paper, we argue for a taxonomy of approaches to function based on different epistemological perspectives assumed with regard to the treatment of this central concept in the life sciences. We distinguish between etiological and organizational perspectives on function, analyzing two distinct theories related to each perspective: Wright’s selectionist etiological approach and Godfrey-Smith’s modern history theory of functions, in the case of the etiological perspective; and Cummins’ functional analysis and Collier’s interactivist approach to function, among organizational accounts. We explain differences and similarities between these theories and the broader perspectives on function, arguing for a particular way of understanding the consensus without unity in debates about function. While explaining the accounts of function, we also deal with the relationship between this concept and other important biological concepts, such as adaptation, selection, complexity, and autonomy. We also advance an argument for the limits and prospects of the explanatory role of function in evolution. By arguing that changes in functionality are always grounded on changes in systems’ organization, we show that function can never explain the origins of traits. Nevertheless, it can explain the spread of traits in populations, but only when we are dealing with functionally novel traits. Finally, we stress that organizational accounts of function are needed to understand how new functions appear by means of changes in systems

  12. c-reactive protein — biological functions, cardiovascular disease ...

    African Journals Online (AJOL)

    CRP are indicative of biological ageing, a non-inflammatory condition.19. Biological properties and functions of cRP. Recognition of pathogens and damaged cells. As part of the acute-phase response, ..... C-reactive protein: a critical update. J Clin Invest 2003;. 111:1805-12. 35. Pepys MB, Baltz ML. Acute phase proteins ...

  13. Genomic Functionalization: The Next Revolution In Biology

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Peter [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Schoeniger, Joseph S. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Imbro, Paula M. [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2014-07-01

    We have implemented a ligand-alignment algorithm into our developed computational pipeline for identifying specificity-determining features (SDFs) in protein-ligand complexes. Given a set of protein-ligand complex structures, the algorithm aligns the complexes by ligand rather than by the C -RMSD or standard approach, providing a single reference frame for extracting SDFs. We anticipate that this ligand-alignment capability will be highly useful for protein function prediction. We already have a database containing > 20 K ligand-protein complex crystal structures taken from the Protein Data Bank. By aligning these proteins to single reference frames using ligand alignment, we can submit the complexes to our pipeline for SDF extraction. The SDFs derived from this training procedure can be used as thumbprints that are hallmarks of individual enzyme classes. These SDF thumbprints may then serve as guides to the prediction of function of new unknown proteins.

  14. Chemical Recycling of Expanded Polystyrene Waste: Synthesis of Novel Functional Polystyrene-Hydrazone Surface for Phenol Removal

    OpenAIRE

    Ali N. Siyal; Saima Q. Memon; Sajida Parveen; Asma Soomro; Khaskheli, Mazhar I.; Khuhawar, M.Y.

    2013-01-01

    Expanded polystyrene (EPS) waste was chemically recycled to a novel functional polystyrene-hydrazone (PSH) surface by acetylation of polystyrene (PS) and then condensation with phenyl hydrazine. The synthesized surface was characterized by the FT-IR and elemental analysis. Synthesized novel functional PSH surface was successfully applied for the treatment of phenol-contaminated industrial wastewater by solid-phase extraction. Multivariant sorption optimization was achieved by factorial design...

  15. Conception of Biologic System: Basis Functional Elements and Metric Properties

    Directory of Open Access Journals (Sweden)

    Garri Davydyan

    2014-01-01

    Full Text Available A notion of biologic system or just a system implies a functional wholeness of comprising system components. Positive and negative feedback are the examples of how the idea to unite anatomical elements in the whole functional structure was successfully used in practice to explain regulatory mechanisms in biology and medicine. There are numerous examples of functional and metabolic pathways which are not regulated by feedback loops and have a structure of reciprocal relationships. Expressed in the matrix form positive feedback, negative feedback, and reciprocal links represent three basis elements of a Lie algebra sl(2,ℝ of a special linear group SL(2,ℝ. It is proposed that the mathematical group structure can be realized through the three regulatory elements playing a role of a functional basis of biologic systems. The structure of the basis elements endows the space of biological variables with indefinite metric. Metric structure resembles Minkowski's space-time (+, −, − making the carrier spaces of biologic variables and the space of transformations inhomogeneous. It endows biologic systems with a rich functional structure, giving the regulatory elements special differentiating features to form steady autonomous subsystems reducible to one-dimensional components.

  16. The Multisystemic and Multilevel Investigation of the Expanded Therapeutic Alliance-Psychological Functioning Relationship in Individual Therapy.

    Science.gov (United States)

    Karam, Eli A; Ko, Mei-Ju; Pinsof, Bill; Mroczek, Daniel; Sprenkle, Douglas

    2015-10-01

    The expanded therapeutic alliance, consisting of multiple interpersonal alliance relationships, is a common factor inherent to the practice of all systemic therapies. The following study has three specific aims: (a) Bring an expanded, multisystemic emphasis to the study of the therapeutic alliance in individual therapy; (b) Understand better the session-by-session relationship between alliance and psychological functioning, including distinguishing within-person from between-person variability by using multilevel modeling techniques; and (c) Explore the role of early attachment relationships and family-of-origin experiences in moderating the alliance-psychological functioning relationship. Instead of taking only one or two alliance measurements throughout treatment like in the majority of previous research, we measured both alliance and psychological functioning continuously at each session for 296 subjects. © 2014 American Association for Marriage and Family Therapy.

  17. Form and function: Perspectives on structural biology and resources for the future

    Energy Technology Data Exchange (ETDEWEB)

    Vaughan, D. (ed.)

    1990-12-01

    The purpose of this study is largely to explore and expand on the thesis that biological structures and their functions are suited to. Form indeed follows function and if we are to understand the workings of a living system, with all that such an understanding promises, we must first seek to describe the structure of its parts. Descriptions of a few achievements of structural biology lay the groundwork, but the substance of this booklet is a discussion of important questions yet unanswered and opportunities just beyond our grasp. The concluding pages then outline a course of action in which the Department of Energy would exercise its responsibility to develop the major resources needed to extend our reach and to answer some of those unanswered questions. 22 figs.

  18. A dynamic model for functional mapping of biological rhythms.

    Science.gov (United States)

    Fu, Guifang; Luo, Jiangtao; Berg, Arthur; Wang, Zhong; Li, Jiahan; Das, Kiranmoy; Li, Runze; Wu, Rongling

    2011-01-01

    Functional mapping is a statistical method for mapping quantitative trait loci (QTLs) that regulate the dynamic pattern of a biological trait. This method integrates mathematical aspects of biological complexity into a mixture model for genetic mapping and tests the genetic effects of QTLs by comparing genotype-specific curve parameters. As a way of quantitatively specifying the dynamic behavior of a system, differential equations have proven to be powerful for modeling and unraveling the biochemical, molecular, and cellular mechanisms of a biological process, such as biological rhythms. The equipment of functional mapping with biologically meaningful differential equations provides new insights into the genetic control of any dynamic processes. We formulate a new functional mapping framework for a dynamic biological rhythm by incorporating a group of ordinary differential equations (ODE). The Runge-Kutta fourth order algorithm was implemented to estimate the parameters that define the system of ODE. The new model will find its implications for understanding the interplay between gene interactions and developmental pathways in complex biological rhythms.

  19. Evidence for a Role of Executive Functions in Learning Biology

    Science.gov (United States)

    Rhodes, Sinéad M.; Booth, Josephine N.; Campbell, Lorna Elise; Blythe, Richard A.; Wheate, Nial J.; Delibegovic, Mirela

    2014-01-01

    Research examining cognition and science learning has focused on working memory, but evidence implicates a broader set of executive functions. The current study examined executive functions and learning of biology in young adolescents. Fifty-six participants, aged 12-13?years, completed tasks of working memory (Spatial Working Memory), inhibition…

  20. Exploring the potential impact of an expanded genetic code on protein function

    OpenAIRE

    Xiao, Han; Nasertorabi, Fariborz; Choi, Sei-hyun; Han, Gye Won; Reed, Sean A.; Stevens, Raymond C.; Schultz, Peter G.

    2015-01-01

    We describe a general strategy that begins to allow us to address the question of whether an expanded genetic code provides an evolutionary advantage to an organism. A large library of β-lactamase variants with distinct noncanonical amino acids substituted randomly at single sites throughout the protein was generated and then subjected to an antibiotic growth-based screen to identify mutants with enhanced catalytic activity. We show that a unique noncanonical mutation in the enzyme β-lactamas...

  1. The physical characteristics of human proteins in different biological functions.

    Science.gov (United States)

    Wang, Tengjiao; Tang, Hailin

    2017-01-01

    The physical properties of gene products are the foundation of their biological functions. In this study, we systematically explored relationships between physical properties and biological functions. The physical properties including origin time, evolution pressure, mRNA and protein stability, molecular weight, hydrophobicity, acidity/alkaline, amino acid compositions, and chromosome location. The biological functions are defined from 4 aspects: biological process, molecular function, cellular component and cell/tissue/organ expression. We found that the proteins associated with basic material and energy metabolism process originated earlier, while the proteins associated with immune, neurological system process etc. originated later. Tissues may have a strong influence on evolution pressure. The proteins associated with energy metabolism are double-stable. Immune and peripheral cell proteins tend to be mRNA stable/protein unstable. There are very few function items with double-unstable of mRNA and protein. The proteins involved in the cell adhesion tend to consist of large proteins with high proportion of small amino acids. The proteins of organic acid transport, neurological system process and amine transport have significantly high hydrophobicity. Interestingly, the proteins involved in olfactory receptor activity tend to have high frequency of aromatic, sulfuric and hydroxyl amino acids.

  2. Chemical Recycling of Expanded Polystyrene Waste: Synthesis of Novel Functional Polystyrene-Hydrazone Surface for Phenol Removal

    Directory of Open Access Journals (Sweden)

    Ali N. Siyal

    2013-01-01

    Full Text Available Expanded polystyrene (EPS waste was chemically recycled to a novel functional polystyrene-hydrazone (PSH surface by acetylation of polystyrene (PS and then condensation with phenyl hydrazine. The synthesized surface was characterized by the FT-IR and elemental analysis. Synthesized novel functional PSH surface was successfully applied for the treatment of phenol-contaminated industrial wastewater by solid-phase extraction. Multivariant sorption optimization was achieved by factorial design approach. 99.93% of phenol was removed from aqueous solution. FT-IR study showed the involvement of nitrogen of hydrazone moiety of synthesized surface for the uptake of phenol through the hydrogen bonding.

  3. Expression of the activation antigen CD69 predicts functionality of in vitro expanded peripheral blood mononuclear cells (PBMC) from healthy donors and HIV-infected patients

    DEFF Research Database (Denmark)

    Nielsen, S D; Afzelius, P; Ersbøll, A K

    1998-01-01

    Gene therapy for AIDS necessitates harvest and expansion of PBMC from HIV-infected patients. We expanded PBMC from healthy blood donors and HIV-infected patients for up to 14 days using four expansion protocols: 3 days of phytohaemagglutinin (PHA) stimulation, continuous PHA stimulation, 3 days...... cytometry. PBMC from healthy donors and HIV-infected patients were readily expanded. The best expansion was obtained using stimulation for 3 days. After expansion, functionality of PBMC measured as proliferative response was partly conserved. PBMC expanded with stimulation for 3 days exhibited more...... preserved functionality than PBMC stimulated continuously (P healthy donors expanded with PHA stimulation for 3 days...

  4. Uncovering Biological Network Function via Graphlet Degree Signatures

    Directory of Open Access Journals (Sweden)

    Nataša Pržulj

    2008-01-01

    Full Text Available Motivation: Proteins are essential macromolecules of life and thus understanding their function is of great importance. The number of functionally unclassified proteins is large even for simple and well studied organisms such as baker’s yeast. Methods for determining protein function have shifted their focus from targeting specific proteins based solely on sequence homology to analyses of the entire proteome based on protein-protein interaction (PPI networks. Since proteins interact to perform a certain function, analyzing structural properties of PPI networks may provide useful clues about the biological function of individual proteins, protein complexes they participate in, and even larger subcellular machines.Results: We design a sensitive graph theoretic method for comparing local structures of node neighborhoods that demonstrates that in PPI networks, biological function of a node and its local network structure are closely related. The method summarizes a protein’s local topology in a PPI network into the vector of graphlet degrees called the signature of the protein and computes the signature similarities between all protein pairs. We group topologically similar proteins under this measure in a PPI network and show that these protein groups belong to the same protein complexes, perform the same biological functions, are localized in the same subcellular compartments, and have the same tissue expressions. Moreover, we apply our technique on a proteome-scale network data and infer biological function of yet unclassified proteins demonstrating that our method can provide valuable guidelines for future experimental research such as disease protein prediction.Availability: Data is available upon request.

  5. Biological ensilage of fish : optimization of stability, safety and functionality

    NARCIS (Netherlands)

    Enes Dapkevicius, M.L.N.

    2002-01-01

    This thesis deals with stability, safety, and functionality aspects of biological fish silage (BFS) obtained by lactic acid fermentation. BFS may provide an economically viable, environment friendly way of upgrading fish waste.

    BFS has been found advantageous when compared to the

  6. Functional and biological characteristics of asthma in cleaning workers.

    NARCIS (Netherlands)

    Vizcaya, D.; Mirabelli, M.C.; Orriols, R.; Antó, J.M.; Barreiro, E.; Burgos, F.; Arjona, L.; Gomez, F.; Zock, J.P.

    2013-01-01

    Objectives: Cleaning workers have an increased risk of asthma but the underlying mechanisms are largely unknown. We studied functional and biological characteristics in asthmatic cleaners and compared these to healthy cleaners. Methods: Forty-two cleaners with a history of asthma and/or recent

  7. The functioning and behaviour of biological parents of children ...

    African Journals Online (AJOL)

    Parenting a child with ADHD may intensify parental stress through functional impairment notwithstanding the diagnosis of ADHD. Methods: Eighty-one biological parents of children diagnosed with attention-deficit/ hyperactivity disorder were screened using self-reporting measurements. ADHD self-report scale (ASRS-V 1.1) ...

  8. Evolutionary cell biology: functional insight from "endless forms most beautiful".

    Science.gov (United States)

    Richardson, Elisabeth; Zerr, Kelly; Tsaousis, Anastasios; Dorrell, Richard G; Dacks, Joel B

    2015-12-15

    In animal and fungal model organisms, the complexities of cell biology have been analyzed in exquisite detail and much is known about how these organisms function at the cellular level. However, the model organisms cell biologists generally use include only a tiny fraction of the true diversity of eukaryotic cellular forms. The divergent cellular processes observed in these more distant lineages are still largely unknown in the general scientific community. Despite the relative obscurity of these organisms, comparative studies of them across eukaryotic diversity have had profound implications for our understanding of fundamental cell biology in all species and have revealed the evolution and origins of previously observed cellular processes. In this Perspective, we will discuss the complexity of cell biology found across the eukaryotic tree, and three specific examples of where studies of divergent cell biology have altered our understanding of key functional aspects of mitochondria, plastids, and membrane trafficking. © 2015 Richardson 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).

  9. Milk protein tailoring to improve functional and biological properties

    Directory of Open Access Journals (Sweden)

    JEAN-MARC CHOBERT

    2012-01-01

    Full Text Available Proteins are involved in every aspects of life: structure, motion, catalysis, recognition and regulation. Today's highly sophisticated science of the modifications of proteins has ancient roots. The tailoring of proteins for food and medical uses precedes the beginning of what is called biochemistry. Chemical modification of proteins was pursued early in the twentieth century as an analytical procedure for side-chain amino acids. Later, methods were developed for specific inactivation of biologically active proteins and titration of their essential groups. Enzymatic modifications were mainly developed in the seventies when many more enzymes became economically available. Protein engineering has become a valuable tool for creating or improving proteins for practical use and has provided new insights into protein structure and function. The actual and potential use of milk proteins as food ingredients has been a popular topic for research over the past 40 years. With today's sophisticated analytical, biochemical and biological research tools, the presence of compounds with biological activity has been demonstrated. Improvements in separation techniques and enzyme technology have enabled efficient and economic isolation and modification of milk proteins, which has made possible their use as functional foods, dietary supplements, nutraceuticals and medical foods. In this review, some chemical and enzymatic modifications of milk proteins are described, with particular focus on their functional and biological properties.

  10. Expanding the Pillararene Chemistry: Synthesis and Application of a 10 + 1 Functionalized Pillar[5]arene.

    Science.gov (United States)

    Bojtár, Márton; Simon, András; Bombicz, Petra; Bitter, István

    2017-09-01

    A novel functionality was introduced in the pillararene family by the Claisen rearrangement of monoallyl pillar[5]arene. This new key derivative can lead to the formation of a 10 + 1 functionalized derivative, a useful scaffold for further derivatization. Except for the previously known monodeprotection reaction, all steps proceed efficiently with high yields and easy separation. In addition, a solvent-responsive pseudo[1]rotaxane was synthesized based on this novel functionality.

  11. Expanding functional repertoires of fungal peroxisomes: contribution to growth and survival processes

    OpenAIRE

    Jun-ichi eMARUYAMA; Katsuhiko eKITAMOTO

    2013-01-01

    It has long been regarded that the primary function of fungal peroxisomes is limited to the β-oxidation of fatty acids, as mutants lacking peroxisomal function fail to grow in minimal medium containing fatty acids as the sole carbon source. However, studies in filamentous fungi have revealed that peroxisomes have diverse functional repertoires. This review describes the essential roles of peroxisomes in the growth and survival processes of filamentous fungi. One such survival mechanism involv...

  12. The correlation function for density perturbations in an expanding universe. II - Nonlinear theory

    Science.gov (United States)

    Mcclelland, J.; Silk, J.

    1977-01-01

    A formalism is developed to find the two-point and higher-order correlation functions for a given distribution of sizes and shapes of perturbations which are randomly placed in three-dimensional space. The perturbations are described by two parameters such as central density and size, and the two-point correlation function is explicitly related to the luminosity function of groups and clusters of galaxies

  13. Surface functionalization of quantum dots for biological applications.

    Science.gov (United States)

    Karakoti, Ajay Singh; Shukla, Ritesh; Shanker, Rishi; Singh, Sanjay

    2015-01-01

    Quantum dots are a group of inorganic nanomaterials exhibiting exceptional optical and electronic properties which impart distinct advantages over traditional fluorescent organic dyes in terms of tunable broad excitation and narrow emission spectra, signal brightness, high quantum yield and photo-stability. Aqueous solubility and surface functionalization are the most common problems for QDs employed in biological research. This review addresses the recent research progress made to improve aqueous solubility, functionalization of biomolecules to QD surface and the poorly understood chemistry involved in the steps of bio-functionalization of such nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. An expanded evaluation of protein function prediction methods shows an improvement in accuracy

    National Research Council Canada - National Science Library

    ...; Jiang, Yuxiang; Oron, Tal Ronnen; Clark, Wyatt T; Bankapur, Asma R; Anea, D', Daniel; Lepore, Rosalba; Funk, Christopher S; Kahanda, Indika; Verspoor, Karin M; Ben-Hur, Asa; Koo, Da Chen Emily; Penfold-Brown, Duncan; Shasha, Dennis; Youngs, Noah; Bonneau, Richard; Lin, Alexana; Sahraeian, Sayed M.E; Martelli, Pier Luigi; ti, Giuseppe; Casadio, Rita; Cao, Renzhi; Zhong, Zhaolong; Cheng, Jianlin; Altenhoff, Aian; Skunca, Nives; Dessimoz, Christophe; Dogan, Tunca; Hakala, Kai; Kaewphan, Suwisa; Mehryary, Farrokh; Salakoski, Tapio; Ginter, Filip; Fang, Hai; Smithers, Ben; Oates, Matt; Gough, Julian; Törönen, Petri; Koskinen, Patrik; Holm, Liisa; Chen, Ching Tai; Hsu, Wen Lian; Bryson, Kevin; Cozzetto, Domenico; Minneci, Federico; Jones, David T; Chapman, Samuel; BKC, Dukka; Khan, Ishita K; Kihara, Daisuke; Ofer, Dan; Rappoport, Nadav; Stern, Amos; Cibrian-Uhalte, Elena; Denny, Paul; Foulger, Rebecca E; Hieta, Reija; Legge, Duncan; Lovering, Ruth C; Magrane, Michele; Melidoni, Anna N; Mutowo-Meullenet, Prudence; Pichler, Klemens; Shypitsyna, Aleksana; Li, Biao; Zakeri, Pooya; ElShal, Sarah; Tranchevent, Léon Charles; Das, Sayoni; Dawson, Natalie L; Lee, David; Lees, Jonathan G; Sillitoe, Ian; Bhat, Prajwal; Nepusz, Tamás; Romero, Alfonso E; Sasidharan, Rajkumar; Yang, Haixuan; Paccanaro, Alberto; Gillis, Jesse; Sedeño-Cortés, Aiana E; Pavlidis, Paul; Feng, Shou; Cejuela, Juan M; Goldberg, Tatyana; Hamp, Tobias; Richter, Lothar; Salamov, Asaf; Gabaldon, Toni; Marcet-Houben, Marina; Supek, Fran; Gong, Qingtian; Ning, Wei; Zhou, Yuanpeng; Tian, Weidong; Falda, Marco; Fontana, Paolo; Lavezzo, Enrico; Toppo, Stefano; Ferrari, Carlo; Giollo, Manuel

    2016-01-01

    .... While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction...

  15. Expanding the Concepts in Protein Structure-Function Relationships and Enzyme Kinetics: Teaching Using Morpheeins

    Science.gov (United States)

    Lawrence, Sarah H.; Jaffe, Eileen K.

    2008-01-01

    A morpheein is a homo-oligomeric protein that can exist as an ensemble of physiologically significant and functionally distinct alternate quaternary assemblies. Morpheeins exist in nature and use conformational equilibria between different tertiary structures to form distinct oligomers as a means of regulating their function. Notably, alternate…

  16. Current functional metagenomic approaches only expand the existing protease sequence space, but does not presently add any novelty to it.

    Science.gov (United States)

    Morris, Laura S; Marchesi, Julian R

    2015-01-01

    Proteases are a fundamental function in many organisms and thus many ecosystems and yet they are rarely obtained in functional metagenomic screens. Here, we have isolated an active protease gene (M1-2; 613 amino acids) which resided in a 38.4 kb fosmid clone that showed a classical protease-positive phenotype. It was classified as a zinc-dependent metalloprotease, with the closest annotated sequence as a neutral protease from Collimonas fungivorans (62 % similarity and 72 % homology). Further characterisation showed that its optimum temperature and pH were 42 °C and 8.0, respectively. Activity was inhibited by EDTA, but inhibition started to be reversed by excess Zn(2+). A putative signal peptide was identified bioinformatically and this may be why this protease was successfully isolated using a functional metagenomic screen. Bioinformatic analysis shows that this does not represent a novel protease, but simply expands the current sequence space of known proteases.

  17. Expanding the neurological examination using functional neurologic assessment: part II neurologic basis of applied kinesiology.

    Science.gov (United States)

    Schmitt, W H; Yanuck, S F

    1999-03-01

    Functional Neurologic Assessment and treatment methods common to the practice of applied kinesiology are presented. These methods are proposed to enhance neurological examination and treatment procedures toward more effective assessment and care of functional impairment. A neurologic model for these procedures is proposed. Manual assessment of muscular function is used to identify changes associated with facilitation and inhibition, in response to the introduction of sensory receptor-based stimuli. Muscle testing responses to sensory stimulation of known value are compared with usually predictable patterns based on known neuroanatomy and neurophysiology, guiding the clinician to an understanding of the functional status of the patient's nervous system. These assessment procedures are used in addition to other standard diagnostic measures to augment rather than replace the existing diagnostic armamentarium. The proper understanding of the neurophysiologic basis of muscle testing procedures will assist in the design of further investigations into applied kinesiology. Accordingly, the neurophysiologic basis and proposed mechanisms of these methods are reviewed.

  18. Balancing ecosystem function, services and disservices resulting from expanding goose populations

    NARCIS (Netherlands)

    Buij, Ralph; Melman, Theodorus C.P.; Loonen, Maarten J.J.E.; Fox, Anthony D.

    2017-01-01

    As goose populations increase in abundance, their influence on ecological processes is increasing. We review the evidence for key ecological functions of wild goose populations in Eurasia and North America, including aquatic invertebrate and plant propagule transport, nutrient deposition in

  19. Expanded functional coupling of subcortical nuclei with the motor resting-state network in multiple sclerosis

    DEFF Research Database (Denmark)

    Dogonowski, Anne-Marie; Siebner, Hartwig R; Sørensen, Per Soelberg

    2013-01-01

    BACKGROUND: Multiple sclerosis (MS) impairs signal transmission along cortico-cortical and cortico-subcortical connections, affecting functional integration within the motor network. Functional magnetic resonance imaging (fMRI) during motor tasks has revealed altered functional connectivity in MS...... controls underwent a 20-minute resting-state fMRI session at 3 Tesla. Independent component analysis was applied to the fMRI data to identify disease-related changes in motor resting-state connectivity. RESULTS: Patients with MS showed a spatial expansion of motor resting-state connectivity in deep...... subcortical nuclei but not at the cortical level. The anterior and middle parts of the putamen, adjacent globus pallidus, anterior and posterior thalamus and the subthalamic region showed stronger functional connectivity with the motor network in the MS group compared with controls. CONCLUSION: MS...

  20. Expanded functional coupling of subcortical nuclei with the motor resting-state network in multiple sclerosis.

    Science.gov (United States)

    Dogonowski, Anne-Marie; Siebner, Hartwig R; Sørensen, Per Soelberg; Wu, Xingchen; Biswal, Bharat; Paulson, Olaf B; Dyrby, Tim B; Skimminge, Arnold; Blinkenberg, Morten; Madsen, Kristoffer H

    2013-04-01

    Multiple sclerosis (MS) impairs signal transmission along cortico-cortical and cortico-subcortical connections, affecting functional integration within the motor network. Functional magnetic resonance imaging (fMRI) during motor tasks has revealed altered functional connectivity in MS, but it is unclear how much motor disability contributed to these abnormal functional interaction patterns. To avoid any influence of impaired task performance, we examined disease-related changes in functional motor connectivity in MS at rest. A total of 42 patients with MS and 30 matched controls underwent a 20-minute resting-state fMRI session at 3 Tesla. Independent component analysis was applied to the fMRI data to identify disease-related changes in motor resting-state connectivity. Patients with MS showed a spatial expansion of motor resting-state connectivity in deep subcortical nuclei but not at the cortical level. The anterior and middle parts of the putamen, adjacent globus pallidus, anterior and posterior thalamus and the subthalamic region showed stronger functional connectivity with the motor network in the MS group compared with controls. MS is characterised by more widespread motor connectivity in the basal ganglia while cortical motor resting-state connectivity is preserved. The expansion of subcortical motor resting-state connectivity in MS indicates less efficient funnelling of neural processing in the executive motor cortico-basal ganglia-thalamo-cortical loops.

  1. Early changes in pulmonary function after vertical expandable prosthetic titanium rib insertion in children with thoracic insufficiency syndrome.

    Science.gov (United States)

    Mayer, Oscar Henry; Redding, Gregory

    2009-01-01

    The vertical expandable prosthetic titanium rib (VEPTR) has been inserted in children with thoracic insufficiency syndrome for the last decade to expand and support the chest and allow for further lung growth. There are minimal published data evaluating the postoperative change in lung function after VEPTR insertion. We hypothesize that there will be a significant increase in lung function after VEPTR insertion, and the earlier the insertion, the greater the improvement. The Chest Wall Disorders Study Group Database, containing data before and after VEPTR insertion from 7 different centers, was queried for spirometry and lung volume measurements, and the data were analyzed to assess the short-term effect on lung function of VEPTR placement. There was a statistically significant decrease in forced vital capacity, forced expiratory volume in 1 second as a percent of predicted, an increase in residual volume (RV) that did not reach statistical significance, and there was no change in total lung capacity at the first postoperative visit (7.7 +/- 4.8 months). There was a significant decrease in Cobb angle. There was no correlation between absolute change in any pulmonary function and Cobb angle age at the time of surgery. Although there is a clinically and radiographically apparent expansion of the thorax after VEPTR insertion, there is no similar improvement in lung volume, and instead there is a decrease in forced vital capacity and increase in residual volume, the explanation for which requires further study. This lack of change in pulmonary function after VEPTR insertion suggests that the benefit of VEPTR insertion may lie more in stabilizing the thorax and improving respiratory mechanics measured in other ways.

  2. Knowledge base and functionality of concepts of some Filipino biology teachers in five biology topics

    Science.gov (United States)

    Barquilla, Manuel B.

    2018-01-01

    This mixed research, is a snapshot of some Filipino Biology teachers' knowledge structure and how their concepts of the five topics in Biology (Photosynthesis, Cellular Respiration, human reproductive system, Mendelian genetics and NonMendelian genetics) functions and develops inside a biology classroom. The study focuses on the six biology teachers and a total of 222 students in their respective classes. Of the Six (6) teachers, three (3) are under the Science curriculum and the other three (3) are under regular curriculum in both public and private schools in Iligan city and Lanao del Norte, Philippines. The study utilized classroom discourses, concept maps, interpretative case-study method, bracketing method, and concept analysis for qualitative part; the quantitative part uses a nonparametric statistical tool, Kendall's tau Coefficient for determining relationship and congruency while measures of central tendencies and dispersion (mean, and standard deviation) for concept maps scores interpretation. Knowledge Base of Biology teachers were evaluated by experts in field of specialization having a doctorate program (e.g. PhD in Genetics) and PhD Biology candidates. The data collection entailed seven (7) months immersion: one (1) month for preliminary phase for the researcher to gain teachers' and students' confidence and the succeeding six (6) months for main observation and data collection. The evaluation of teachers' knowledge base by experts indicated that teachers' knowledge of (65%) is lower than the minimum (75%) recommended by ABD-el-Khalick and Boujaoude (1997). Thus, the experts believe that content knowledge of the teachers is hardly adequate for their teaching assignment. Moreover, the teachers in this study do not systematically use reallife situation to apply the concepts they teach. They can identify concepts too abstract for their student; however, they seldom use innovative ways to bring the discussion to their students' level of readiness and

  3. 'Function' Revisited: Expanding the role of translation in the receptor context

    Directory of Open Access Journals (Sweden)

    Maria Lucia Barbosa de Vasconcellos

    1996-01-01

    Full Text Available One well-known problem in any field of investigation is the difficulty of overcoming the lack of terminological consistency in the treatment of basic issues within a specific area. Such inconsistency is not only misleading in that it may confuse readers as to the reference of theconcept referred to, but also dangerous in that it can completely undermine the claims and arguments put forward by the author usingthe notion. I am aiming this comment at a central lack of clarity concerning the concept of FUNCTION as used by Roberts (1992: 1-16,in her article "The Concept of Function of Translation and Its Application to Literary Texts".

  4. Bioclojure: a functional library for the manipulation of biological sequences.

    Science.gov (United States)

    Plieskatt, Jordan; Rinaldi, Gabriel; Brindley, Paul J; Jia, Xinying; Potriquet, Jeremy; Bethony, Jeffrey; Mulvenna, Jason

    2014-09-01

    BioClojure is an open-source library for the manipulation of biological sequence data written in the language Clojure. BioClojure aims to provide a functional framework for the processing of biological sequence data that provides simple mechanisms for concurrency and lazy evaluation of large datasets. BioClojure provides parsers and accessors for a range of biological sequence formats, including UniProtXML, Genbank XML, FASTA and FASTQ. In addition, it provides wrappers for key analysis programs, including BLAST, SignalP, TMHMM and InterProScan, and parsers for analyzing their output. All interfaces leverage Clojure's functional style and emphasize laziness and composability, so that BioClojure, and user-defined, functions can be chained into simple pipelines that are thread-safe and seamlessly integrate lazy evaluation. BioClojure is distributed under the Lesser GPL, and the source code is freely available from GitHub (https://github.com/s312569/clj-biosequence). © The Author 2014. Published by Oxford University Press.

  5. Biological framework for soil aggregation: Implications for ecological functions.

    Science.gov (United States)

    Ghezzehei, Teamrat; Or, Dani

    2016-04-01

    Soil aggregation is heuristically understood as agglomeration of primary particles bound together by biotic and abiotic cementing agents. The organization of aggregates is believed to be hierarchical in nature; whereby primary particles bond together to form secondary particles and subsequently merge to form larger aggregates. Soil aggregates are not permanent structures, they continuously change in response to internal and external forces and other drivers, including moisture, capillary pressure, temperature, biological activity, and human disturbances. Soil aggregation processes and the resulting functionality span multiple spatial and temporal scales. The intertwined biological and physical nature of soil aggregation, and the time scales involved precluded a universally applicable and quantifiable framework for characterizing the nature and function of soil aggregation. We introduce a biophysical framework of soil aggregation that considers the various modes and factors of the genesis, maturation and degradation of soil aggregates including wetting/drying cycles, soil mechanical processes, biological activity and the nature of primary soil particles. The framework attempts to disentangle mechanical (compaction and soil fragmentation) from in-situ biophysical aggregation and provides a consistent description of aggregate size, hierarchical organization, and life time. It also enables quantitative description of biotic and abiotic functions of soil aggregates including diffusion and storage of mass and energy as well as role of aggregates as hot spots of nutrient accumulation, biodiversity, and biogeochemical cycles.

  6. Deducing protein function by forensic integrative cell biology.

    Science.gov (United States)

    Earnshaw, William C

    2013-12-01

    Our ability to sequence genomes has provided us with near-complete lists of the proteins that compose cells, tissues, and organisms, but this is only the beginning of the process to discover the functions of cellular components. In the future, it's going to be crucial to develop computational analyses that can predict the biological functions of uncharacterised proteins. At the same time, we must not forget those fundamental experimental skills needed to confirm the predictions or send the analysts back to the drawing board to devise new ones.

  7. Functional structure of biological communities predicts ecosystem multifunctionality.

    Directory of Open Access Journals (Sweden)

    David Mouillot

    Full Text Available The accelerating rate of change in biodiversity patterns, mediated by ever increasing human pressures and global warming, demands a better understanding of the relationship between the structure of biological communities and ecosystem functioning (BEF. Recent investigations suggest that the functional structure of communities, i.e. the composition and diversity of functional traits, is the main driver of ecological processes. However, the predictive power of BEF research is still low, the integration of all components of functional community structure as predictors is still lacking, and the multifunctionality of ecosystems (i.e. rates of multiple processes must be considered. Here, using a multiple-processes framework from grassland biodiversity experiments, we show that functional identity of species and functional divergence among species, rather than species diversity per se, together promote the level of ecosystem multifunctionality with a predictive power of 80%. Our results suggest that primary productivity and decomposition rates, two key ecosystem processes upon which the global carbon cycle depends, are primarily sustained by specialist species, i.e. those that hold specialized combinations of traits and perform particular functions. Contrary to studies focusing on single ecosystem functions and considering species richness as the sole measure of biodiversity, we found a linear and non-saturating effect of the functional structure of communities on ecosystem multifunctionality. Thus, sustaining multiple ecological processes would require focusing on trait dominance and on the degree of community specialization, even in species-rich assemblages.

  8. Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions.

    Science.gov (United States)

    Gonen, Tal; Gazit, Tomer; Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

    2017-01-01

    Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.

  9. An expanded evaluation of protein function prediction methods shows an improvement in accuracy

    NARCIS (Netherlands)

    Jiang, Yuxiang; Oron, Tal Ronnen; Clark, Wyatt T.; Bankapur, Asma R.; Andrea, D' Daniel; Lepore, Rosalba; Funk, Christopher S.; Kahanda, Indika; Verspoor, Karin M.; Ben-Hur, Asa; Koo, Da Chen Emily; Penfold-Brown, Duncan; Shasha, Dennis; Youngs, Noah; Bonneau, Richard; Lin, Alexandra; Sahraeian, Sayed M.E.; Martelli, Pier Luigi; Profiti, Giuseppe; Casadio, Rita; Cao, Renzhi; Zhong, Zhaolong; Cheng, Jianlin; Altenhoff, Adrian; Skunca, Nives; Dessimoz, Christophe; Dogan, Tunca; Hakala, Kai; Kaewphan, Suwisa; Mehryary, Farrokh; Salakoski, Tapio; Ginter, Filip; Fang, Hai; Smithers, Ben; Oates, Matt; Gough, Julian; Törönen, Petri; Koskinen, Patrik; Holm, Liisa; Chen, Ching Tai; Hsu, Wen Lian; Bryson, Kevin; Cozzetto, Domenico; Minneci, Federico; Jones, David T.; Chapman, Samuel; BKC, Dukka; Khan, Ishita K.; Kihara, Daisuke; Ofer, Dan; Rappoport, Nadav; Stern, Amos; Cibrian-Uhalte, Elena; Denny, Paul; Foulger, Rebecca E.; Hieta, Reija; Legge, Duncan; Lovering, Ruth C.; Magrane, Michele; Melidoni, Anna N.; Mutowo-Meullenet, Prudence; Pichler, Klemens; Shypitsyna, Aleksandra; Li, Biao; Zakeri, Pooya; ElShal, Sarah; Tranchevent, Léon Charles; Das, Sayoni; Dawson, Natalie L.; Lee, David; Lees, Jonathan G.; Sillitoe, Ian; Bhat, Prajwal; Nepusz, Tamás; Romero, Alfonso E.; Sasidharan, Rajkumar; Yang, Haixuan; Paccanaro, Alberto; Gillis, Jesse; Sedeño-Cortés, Adriana E.; Pavlidis, Paul; Feng, Shou; Cejuela, Juan M.; Goldberg, Tatyana; Hamp, Tobias; Richter, Lothar; Salamov, Asaf; Gabaldon, Toni; Marcet-Houben, Marina; Supek, Fran; Gong, Qingtian; Ning, Wei; Zhou, Yuanpeng; Tian, Weidong; Falda, Marco; Fontana, Paolo; Lavezzo, Enrico; Toppo, Stefano; Ferrari, Carlo; Giollo, Manuel; Piovesan, Damiano; Tosatto, Silvio C.E.; Pozo, del Angela; Fernández, José M.; Maietta, Paolo; Valencia, Alfonso; Tress, Michael L.; Benso, Alfredo; Carlo, Di Stefano; Politano, Gianfranco; Savino, Alessandro; Rehman, Hafeez Ur; Re, Matteo; Mesiti, Marco; Valentini, Giorgio; Bargsten, Joachim W.; Dijk, van Aalt-Jan; Gemovic, Branislava; Glisic, Sanja; Perovic, Vladmir; Veljkovic, Veljko; Veljkovic, Nevena; Almeida-e-Silva, Danillo C.; Vencio, Ricardo Z.N.; Sharan, Malvika; Vogel, Jörg; Kansakar, Lakesh; Zhang, Shanshan; Vucetic, Slobodan; Wang, Zheng; Sternberg, Michael J.E.; Wass, Mark N.; Huntley, Rachael P.; Martin, Maria J.; O'Donovan, Claire; Robinson, Peter N.; Moreau, Yves; Tramontano, Anna; Babbitt, Patricia C.; Brenner, Steven E.; Linial, Michal; Orengo, Christine A.; Rost, Burkhard; Greene, Casey S.; Mooney, Sean D.; Friedberg, Iddo; Radivojac, Predrag

    2016-01-01

    Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role

  10. Gene Therapy for the Treatment of Parkinson’s Disease: The Nature of the Biologics Expands the Future Indications

    Directory of Open Access Journals (Sweden)

    Massimo S. Fiandaca

    2012-06-01

    Full Text Available The pharmaceutical industry’s development of therapeutic medications for the treatment of Parkinson’s disease (PD endures, as a result of the continuing need for better agents, and the increased clinical demand due to the aging population. Each new drug offers advantages and disadvantages to patients when compared to other medical offerings or surgical options. Deep brain stimulation (DBS has become a standard surgical remedy for the effective treatment of select patients with PD, for whom most drug regimens have failed or become refractory. Similar to DBS as a surgical option, gene therapy for the treatment of PD is evolving as a future option. In the four different PD gene therapy approaches that have reached clinical trials investigators have documented an excellent safety profile associated with the stereotactic delivery, viral vectors and doses utilized, and transgenes expressed. In this article, we review the clinically relevant gene therapy strategies for the treatment of PD, concentrating on the published preclinical and clinical results, and the likely mechanisms involved. Based on these presentations, we advance an analysis of how the nature of the gene therapy used may eventually expand the scope and utility for the management of PD.

  11. An Expanding Range of Functions for the Copper Chaperone/Antioxidant Protein Atox1

    OpenAIRE

    Hatori, Yuta; Lutsenko, Svetlana

    2013-01-01

    Significance: Antioxidant protein 1 (Atox1 in human cells) is a copper chaperone for the copper export pathway with an essential role in cellular copper distribution. In vitro, Atox1 binds and transfers copper to the copper-transporting ATPases, stimulating their catalytic activity. Inactivation of Atox1 in cells inhibits maturation of secreted cuproenzymes as well as copper export from cells. Recent Advances: Accumulating data suggest that cellular functions of Atox1 are not limited to its c...

  12. Toward a new data standard for combined marine biological and environmental datasets - expanding OBIS beyond species occurrences

    Directory of Open Access Journals (Sweden)

    Daphnis De Pooter

    2017-01-01

    Full Text Available The Ocean Biogeographic Information System (OBIS is the world’s most comprehensive online, open-access database of marine species distributions. OBIS grows with millions of new species observations every year. Contributions come from a network of hundreds of institutions, projects and individuals with common goals: to build a scientific knowledge base that is open to the public for scientific discovery and exploration and to detect trends and changes that inform society as essential elements in conservation management and sustainable development. Until now, OBIS has focused solely on the collection of biogeographic data (the presence of marine species in space and time and operated with optimized data flows, quality control procedures and data standards specifically targeted to these data. Based on requirements from the growing OBIS community to manage datasets that combine biological, physical and chemical measurements, the OBIS-ENV-DATA pilot project was launched to develop a proposed standard and guidelines to make sure these combined datasets can stay together and are not, as is often the case, split and sent to different repositories. The proposal in this paper allows for the management of sampling methodology, animal tracking and telemetry data, biological measurements (e.g., body length, percent live cover, ... as well as environmental measurements such as nutrient concentrations, sediment characteristics or other abiotic parameters measured during sampling to characterize the environment from which biogeographic data was collected. The recommended practice builds on the Darwin Core Archive (DwC-A standard and on practices adopted by the Global Biodiversity Information Facility (GBIF. It consists of a DwC Event Core in combination with a DwC Occurrence Extension and a proposed enhancement to the DwC MeasurementOrFact Extension. This new structure enables the linkage of measurements or facts - quantitative and qualitative properties - to

  13. Balancing ecosystem function, services and disservices resulting from expanding goose populations.

    Science.gov (United States)

    Buij, Ralph; Melman, Theodorus C P; Loonen, Maarten J J E; Fox, Anthony D

    2017-03-01

    As goose populations increase in abundance, their influence on ecological processes is increasing. We review the evidence for key ecological functions of wild goose populations in Eurasia and North America, including aquatic invertebrate and plant propagule transport, nutrient deposition in terrestrial and aquatic ecosystems, the influence of goose populations on vegetation biomass, carbon storage and methane emission, species diversity and disease transmission. To estimate the implications of their growing abundance for humans, we explore how these functions contribute to the provision of ecosystem services and disservices. We assess the weight, extent and trends among such impacts, as well as the balance of their value to society. We examine key unresolved issues to enable a more balanced assessment of the economic costs or benefits of migratory geese along their flyways, including the spatial and temporal variation in services and their contrasting value to different user groups. Many ecological functions of geese are concluded to provide neither services nor disservices and, ecosystem disservices currently appear to outweigh services, although this varies between regions. We consider an improved quantification of ecosystem services and disservices, and how these vary along population flyways with respect to variation in valuing certain cultural services, and under different management scenarios aimed at reducing their disservices, essential for a more balanced management of goose populations.

  14. Expanding functional repertoires of fungal peroxisomes: contribution to growth and survival processes

    Directory of Open Access Journals (Sweden)

    Jun-ichi eMARUYAMA

    2013-07-01

    Full Text Available It has long been regarded that the primary function of fungal peroxisomes is limited to the β-oxidation of fatty acids, as mutants lacking peroxisomal function fail to grow in minimal medium containing fatty acids as the sole carbon source. However, studies in filamentous fungi have revealed that peroxisomes have diverse functional repertoires. This review describes the essential roles of peroxisomes in the growth and survival processes of filamentous fungi. One such survival mechanism involves the Woronin body, a Pezizomycotina-specific organelle that plugs the septal pore upon hyphal lysis to prevent excessive cytoplasmic loss. A number of reports have demonstrated that Woronin bodies are derived from peroxisomes. Specifically, the Woronin body protein Hex1 is targeted to peroxisomes by peroxisomal targeting sequence 1 (PTS1 and forms a self-assembled structure that buds from peroxisomes to form the Woronin body. Peroxisomal deficiency reduces the ability of filamentous fungi to prevent excessive cytoplasmic loss upon hyphal lysis, indicating that peroxisomes contribute to the survival of these multicellular organisms. Peroxisomes were also recently found to play a vital role in the biosynthesis of biotin, which is an essential cofactor for various carboxylation and decarboxylation reactions. In biotin-prototrophic fungi, peroxisome-deficient mutants exhibit growth defects when grown on glucose as a carbon source due to biotin auxotrophy. The biotin biosynthetic enzyme BioF (7-keto-8-aminopelargonic acid synthase contains a PTS1 motif that is required for both peroxisomal targeting and biotin biosynthesis. In plants, the BioF protein contains a conserved PTS1 motif and is also localized in peroxisomes. These findings indicate that the involvement of peroxisomes in biotin biosynthesis is evolutionarily conserved between fungi and plants, and that peroxisomes play a key role in fungal growth.

  15. Biological properties of extracellular vesicles and their physiological functions

    Directory of Open Access Journals (Sweden)

    María Yáñez-Mó

    2015-05-01

    Full Text Available In the past decade, extracellular vesicles (EVs have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

  16. Biological properties of extracellular vesicles and their physiological functions

    Science.gov (United States)

    Yáñez-Mó, María; Siljander, Pia R.-M.; Andreu, Zoraida; Zavec, Apolonija Bedina; Borràs, Francesc E.; Buzas, Edit I.; Buzas, Krisztina; Casal, Enriqueta; Cappello, Francesco; Carvalho, Joana; Colás, Eva; Silva, Anabela Cordeiro-da; Fais, Stefano; Falcon-Perez, Juan M.; Ghobrial, Irene M.; Giebel, Bernd; Gimona, Mario; Graner, Michael; Gursel, Ihsan; Gursel, Mayda; Heegaard, Niels H. H.; Hendrix, An; Kierulf, Peter; Kokubun, Katsutoshi; Kosanovic, Maja; Kralj-Iglic, Veronika; Krämer-Albers, Eva-Maria; Laitinen, Saara; Lässer, Cecilia; Lener, Thomas; Ligeti, Erzsébet; Linē, Aija; Lipps, Georg; Llorente, Alicia; Lötvall, Jan; Manček-Keber, Mateja; Marcilla, Antonio; Mittelbrunn, Maria; Nazarenko, Irina; Hoen, Esther N.M. Nolte-‘t; Nyman, Tuula A.; O'Driscoll, Lorraine; Olivan, Mireia; Oliveira, Carla; Pállinger, Éva; del Portillo, Hernando A.; Reventós, Jaume; Rigau, Marina; Rohde, Eva; Sammar, Marei; Sánchez-Madrid, Francisco; Santarém, N.; Schallmoser, Katharina; Ostenfeld, Marie Stampe; Stoorvogel, Willem; Stukelj, Roman; Van der Grein, Susanne G.; Vasconcelos, M. Helena; Wauben, Marca H. M.; De Wever, Olivier

    2015-01-01

    In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system. PMID:25979354

  17. Probing the Xenopus laevis inner ear transcriptome for biological function

    Directory of Open Access Journals (Sweden)

    Powers TuShun R

    2012-06-01

    Full Text Available Abstract Background The senses of hearing and balance depend upon mechanoreception, a process that originates in the inner ear and shares features across species. Amphibians have been widely used for physiological studies of mechanotransduction by sensory hair cells. In contrast, much less is known of the genetic basis of auditory and vestibular function in this class of animals. Among amphibians, the genus Xenopus is a well-characterized genetic and developmental model that offers unique opportunities for inner ear research because of the amphibian capacity for tissue and organ regeneration. For these reasons, we implemented a functional genomics approach as a means to undertake a large-scale analysis of the Xenopus laevis inner ear transcriptome through microarray analysis. Results Microarray analysis uncovered genes within the X. laevis inner ear transcriptome associated with inner ear function and impairment in other organisms, thereby supporting the inclusion of Xenopus in cross-species genetic studies of the inner ear. The use of gene categories (inner ear tissue; deafness; ion channels; ion transporters; transcription factors facilitated the assignment of functional significance to probe set identifiers. We enhanced the biological relevance of our microarray data by using a variety of curation approaches to increase the annotation of the Affymetrix GeneChip® Xenopus laevis Genome array. In addition, annotation analysis revealed the prevalence of inner ear transcripts represented by probe set identifiers that lack functional characterization. Conclusions We identified an abundance of targets for genetic analysis of auditory and vestibular function. The orthologues to human genes with known inner ear function and the highly expressed transcripts that lack annotation are particularly interesting candidates for future analyses. We used informatics approaches to impart biologically relevant information to the Xenopus inner ear transcriptome

  18. The correlation function for density perturbations in an expanding universe. I - Linear theory

    Science.gov (United States)

    Mcclelland, J.; Silk, J.

    1977-01-01

    The evolution of the two-point correlation function for adiabatic density perturbations in the early universe is studied. Analytical solutions are obtained for the evolution of linearized spherically symmetric adiabatic density perturbations and the two-point correlation function for these perturbations in the radiation-dominated portion of the early universe. The results are then extended to the regime after decoupling. It is found that: (1) adiabatic spherically symmetric perturbations comparable in scale with the maximum Jeans length would survive the radiation-dominated regime; (2) irregular fluctuations are smoothed out up to the scale of the maximum Jeans length in the radiation era, but regular fluctuations might survive on smaller scales; (3) in general, the only surviving structures for irregularly shaped adiabatic density perturbations of arbitrary but finite scale in the radiation regime are the size of or larger than the maximum Jeans length in that regime; (4) infinite plane waves with a wavelength smaller than the maximum Jeans length but larger than the critical dissipative damping scale could survive the radiation regime; and (5) black holes would also survive the radiation regime and might accrete sufficient mass after decoupling to nucleate the formation of galaxies.

  19. Biomarkers of Aging: From Function to Molecular Biology

    Directory of Open Access Journals (Sweden)

    Karl-Heinz Wagner

    2016-06-01

    Full Text Available Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

  20. Biomarkers of Aging: From Function to Molecular Biology.

    Science.gov (United States)

    Wagner, Karl-Heinz; Cameron-Smith, David; Wessner, Barbara; Franzke, Bernhard

    2016-06-02

    Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

  1. An expanded ostracod-based conductivity transfer function for climate reconstruction in the Levant

    Science.gov (United States)

    Mischke, Steffen; Almogi-Labin, Ahuva; Al-Saqarat, Bety; Rosenfeld, Arik; Elyashiv, Hadar; Boomer, Ian; Stein, Mordechai; Lev, Lilach; Ito, Emi

    2014-06-01

    We present the first modern calibration dataset linking ostracod assemblage composition to water chemistry, and other site-specific variables, in the hydrologically and geopolitically sensitive southern Levant region. A total of 42 ostracod taxa were recorded from the 178 sampled sites in Israel and Jordan. Ilyocypris spp., Heterocypris salina and Cypridopsis vidua are the most abundant taxa. Species strictly confined to freshwater conditions are Prionocypris zenkeri, Gomphocythere ortali and Prionocypris olivaceus. In contrast, H. salina, Bradleytriebella lineata and Cyprideis torosa show high frequencies in brackish waters (waters with higher conductivity). Humphcypris subterranea, G. ortali, P. olivaceus and Cypridopsis elongata apparently prefer flowing waters. Specific conductivity optima and tolerance ranges were calculated for the recorded ostracod species and may be used for the palaeoenvironmental assessment of fossil ostracod assemblages. In addition, a transfer-function for quantitative specific conductivity estimation based on 141 samples was established with weighted averaging partial least squares regression (WA-PLS). The resulting coefficient of determination r2 between observed and predicted conductivity values (0.72) and the root-mean-square error of prediction (RMSEP) in % gradient length (13.1) indicate that conductivity may be reliably estimated from ostracod assemblage data. The transfer function was first applied to last glacial ostracod assemblage data from an archaeological trench in the Sea of Galilee (northern Israel). Relatively large conductivity fluctuations between ca 1 and 7 mS cm-1 were inferred for the period 24-20 cal ka BP. In addition, four episodes of freshwater influx near the site of the trench were identified from the presence of shells of freshwater and stream-dwelling species intermingled with very abundant shells of Cyprideis torosa. The results of our study allow a better use of Quaternary ostracods from the Levant as

  2. Biological and perceived stress in motor functional neurological disorders.

    Science.gov (United States)

    Apazoglou, Kalliopi; Mazzola, Viridiana; Wegrzyk, Jennifer; Polara, Giulia Frasca; Aybek, Selma

    2017-11-01

    Current models explaining motor functional neurological disorders (FND) integrate both the neurobiological mechanisms underlying symptoms production and the role of psychosocial stressors. Imaging studies have suggested abnormal motor control linked to impaired emotional and stress regulation. However, little is known on the biological stress regulation in FND. Our aim was to study the biological and perceived response to stress in patients with motor FND. Sixteen patients with motor FND (DSM-5 criteria) and fifteen healthy controls underwent the Trier Social Stress Test. Hypothalamo-pituitary-adrenal axis (HPA) response was evaluated with salivary cortisol and autonomous sympathetic response with salivary alpha-amylase. Area under the curve was computed to reflect background levels (AUCg) and change over time (AUCi). Life adversities and perceived subjective stress on a visual analog scale (VAS) were correlated with biological responses. FND patients had significantly higher background levels (AUCg) of both stress markers (cortisol and amylase) than controls. The biological response (AUCi) to stress did not differ between groups for both markers but the subjective response showed an interaction effect with patients reporting higher levels of stress than controls. After stress, controls showed a strong correlation between subjective and objective sympathetic values (amylase) but not patients. The number and subjective impact of adverse life events correlated with cortisol AUCg in patients only. This study confirms a baseline HPA-axis and sympathetic hyperarousal state in motor FND related to life adversities. During a social stress, dissociation between perceived stress and biological markers was observed in patients only, reflecting a dysregulation of interoception capacity, which might represent an endophenotype of this disorder. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Expanded human blood-derived γδT cells display potent antigen-presentation functions

    Directory of Open Access Journals (Sweden)

    Mohd Wajid Ali Khan

    2014-07-01

    Full Text Available Cell-based immunotherapy strategies target tumors directly (via cytolytic effector cells or aim at mobilizing endogenous anti-tumor immunity. The latter approach includes dendritic cells (DC, most frequently in the form of in vitro cultured peripheral blood monocytes-derived DC. Human blood γδT cells are selective for a single class of non-peptide agonists (phosphoantigens and develop into potent antigen-presenting cells (APC, termed γδT-APC, within 1-3 days of in vitro culture. Availability of large numbers of γδT-APC would be advantageous for use as a novel cellular vaccine. We here report optimal γδT cell expansion (>107 cells/ml blood when peripheral blood mononuclear cells (PBMC from healthy individuals and melanoma patients were stimulated with zoledronate and then cultured for 14 days in the presence of IL-2 and IL-15, yielding γδT cell cultures of variable purity (77±21% and 56±26%, respectively. They resembled effector-memory αβT (TEM cells and retained full functionality as assessed by in vitro tumor cell killing as well as secretion of proinflammatory cytokines (IFNγ, TNFα and cell proliferation in response to stimulation with phosphoantigens. Importantly, day 14 γδT cells expressed numerous APC-related cell surface markers and, in agreement, displayed potent in vitro APC functions. Day 14 γδT cells from PBMC of patients with cancer were equally effective as their counterparts derived from blood of healthy individuals and triggered potent CD8+ αβT cell responses following processing and cross-presentation of simple (influenza M1 and complex (tuberculin purified protein derivative protein antigens. Of note, and in clear contrast to peripheral blood γδT cells, the ability of day 14 γδT cells to trigger antigen-specific αβT cell responses did not depend on re-stimulation. We conclude that day 14 γδT cell cultures provide a convenient source of autologous APC for use in immunotherapy of

  4. Functional toxicogenomic profiling expands insight into modulators of formaldehyde toxicity in yeast

    Directory of Open Access Journals (Sweden)

    Matthew North

    2016-11-01

    Full Text Available Formaldehyde (FA is a commercially important chemical with numerous and diverse uses. Accordingly, occupational and environmental exposure to FA is prevalent worldwide. Various adverse effects, including nasopharyngeal, sinonasal, and lymphohematopoietic cancers, have been linked to FA exposure, prompting designation of FA as a human carcinogen by U.S. and international scientific entities. Although the mechanism(s of FA toxicity have been well studied, additional insight is needed in regard to the genetic requirements for FA tolerance. In this study, a functional toxicogenomics approach was utilized in the model eukaryotic yeast Saccharomyces cerevisiae to identify genes and cellular processes modulating the cellular toxicity of FA. Our results demonstrate mutant strains deficient in multiple DNA repair pathways–including homologous recombination, single strand annealing, and postreplication repair–were sensitive to FA, indicating FA may cause various forms of DNA damage in yeast. The SKI complex and its associated factors, which regulate mRNA degradation by the exosome, were also required for FA tolerance, suggesting FA may have unappreciated effects on RNA stability. Furthermore, various strains involved in osmoregulation and stress response were sensitive to FA. Together, our results are generally consistent with FA-mediated damage to both DNA and RNA. Considering DNA repair and RNA degradation pathways are evolutionarily conserved from yeast to humans, mechanisms of FA toxicity identified in yeast may be relevant to human disease and genetic susceptibility.

  5. Functional annotation of chemical libraries across diverse biological processes.

    Science.gov (United States)

    Piotrowski, Jeff S; Li, Sheena C; Deshpande, Raamesh; Simpkins, Scott W; Nelson, Justin; Yashiroda, Yoko; Barber, Jacqueline M; Safizadeh, Hamid; Wilson, Erin; Okada, Hiroki; Gebre, Abraham A; Kubo, Karen; Torres, Nikko P; LeBlanc, Marissa A; Andrusiak, Kerry; Okamoto, Reika; Yoshimura, Mami; DeRango-Adem, Eva; van Leeuwen, Jolanda; Shirahige, Katsuhiko; Baryshnikova, Anastasia; Brown, Grant W; Hirano, Hiroyuki; Costanzo, Michael; Andrews, Brenda; Ohya, Yoshikazu; Osada, Hiroyuki; Yoshida, Minoru; Myers, Chad L; Boone, Charles

    2017-09-01

    Chemical-genetic approaches offer the potential for unbiased functional annotation of chemical libraries. Mutations can alter the response of cells in the presence of a compound, revealing chemical-genetic interactions that can elucidate a compound's mode of action. We developed a highly parallel, unbiased yeast chemical-genetic screening system involving three key components. First, in a drug-sensitive genetic background, we constructed an optimized diagnostic mutant collection that is predictive for all major yeast biological processes. Second, we implemented a multiplexed (768-plex) barcode-sequencing protocol, enabling the assembly of thousands of chemical-genetic profiles. Finally, based on comparison of the chemical-genetic profiles with a compendium of genome-wide genetic interaction profiles, we predicted compound functionality. Applying this high-throughput approach, we screened seven different compound libraries and annotated their functional diversity. We further validated biological process predictions, prioritized a diverse set of compounds, and identified compounds that appear to have dual modes of action.

  6. Relativistic corrections for non-Born-Oppenheimer molecular wave functions expanded in terms of complex explicitly correlated Gaussian functions

    Science.gov (United States)

    Bubin, Sergiy; Stanke, Monika; Adamowicz, Ludwik

    2017-06-01

    In our previous work S. Bubin et al., Chem. Phys. Lett. 647, 122 (2016), 10.1016/j.cplett.2016.01.056, it was established that complex explicitly correlated one-center all-particle Gaussian functions (CECGs) provide effective basis functions for very accurate nonrelativistic molecular non-Born-Oppenheimer calculations. In this work, we advance the molecular CECGs approach further by deriving and implementing algorithms for calculating the leading relativistic corrections within this approach. The algorithms are tested in the calculations of the corrections for all 23 bound pure vibrational states of the HD+ ion.

  7. Metabolomics for functional genomics, systems biology, and biotechnology.

    Science.gov (United States)

    Saito, Kazuki; Matsuda, Fumio

    2010-01-01

    Metabolomics now plays a significant role in fundamental plant biology and applied biotechnology. Plants collectively produce a huge array of chemicals, far more than are produced by most other organisms; hence, metabolomics is of great importance in plant biology. Although substantial improvements have been made in the field of metabolomics, the uniform annotation of metabolite signals in databases and informatics through international standardization efforts remains a challenge, as does the development of new fields such as fluxome analysis and single cell analysis. The principle of transcript and metabolite cooccurrence, particularly transcriptome coexpression network analysis, is a powerful tool for decoding the function of genes in Arabidopsis thaliana. This strategy can now be used for the identification of genes involved in specific pathways in crops and medicinal plants. Metabolomics has gained importance in biotechnology applications, as exemplified by quantitative loci analysis, prediction of food quality, and evaluation of genetically modified crops. Systems biology driven by metabolome data will aid in deciphering the secrets of plant cell systems and their application to biotechnology.

  8. Functions of MicroRNAs in Cardiovascular Biology and Disease

    Science.gov (United States)

    Hata, Akiko

    2015-01-01

    In 1993, lin-4 was discovered as a critical modulator of temporal development in Caenorhabditis elegans and, most notably, as the first in the class of small, single-stranded noncoding RNAs now defined as microRNAs (miRNAs). Another eight years elapsed before miRNA expression was detected in mammalian cells. Since then, explosive advancements in the field of miRNA biology have elucidated the basic mechanism of miRNA biogenesis, regulation, and gene-regulatory function. The discovery of this new class of small RNAs has augmented the complexity of gene-regulatory programs as well as the understanding of developmental and pathological processes in the cardiovascular system. Indeed, the contributions of miRNAs in cardiovascular development and function have been widely explored, revealing the extensive role of these small regulatory RNAs in cardiovascular physiology. PMID:23157557

  9. Event-based text mining for biology and functional genomics

    Science.gov (United States)

    Thompson, Paul; Nawaz, Raheel; McNaught, John; Kell, Douglas B.

    2015-01-01

    The assessment of genome function requires a mapping between genome-derived entities and biochemical reactions, and the biomedical literature represents a rich source of information about reactions between biological components. However, the increasingly rapid growth in the volume of literature provides both a challenge and an opportunity for researchers to isolate information about reactions of interest in a timely and efficient manner. In response, recent text mining research in the biology domain has been largely focused on the identification and extraction of ‘events’, i.e. categorised, structured representations of relationships between biochemical entities, from the literature. Functional genomics analyses necessarily encompass events as so defined. Automatic event extraction systems facilitate the development of sophisticated semantic search applications, allowing researchers to formulate structured queries over extracted events, so as to specify the exact types of reactions to be retrieved. This article provides an overview of recent research into event extraction. We cover annotated corpora on which systems are trained, systems that achieve state-of-the-art performance and details of the community shared tasks that have been instrumental in increasing the quality, coverage and scalability of recent systems. Finally, several concrete applications of event extraction are covered, together with emerging directions of research. PMID:24907365

  10. Carotenoids from Marine Organisms: Biological Functions and Industrial Applications

    Directory of Open Access Journals (Sweden)

    Christian Galasso

    2017-11-01

    Full Text Available As is the case for terrestrial organisms, carotenoids represent the most common group of pigments in marine environments. They are generally biosynthesized by all autotrophic marine organisms, such as bacteria and archaea, algae and fungi. Some heterotrophic organisms also contain carotenoids probably accumulated from food or partly modified through metabolic reactions. These natural pigments are divided into two chemical classes: carotenes (such as lycopene and α- and β-carotene that are composed of hydrogen and carbon; xanthophylls (such as astaxanthin, fucoxanthin and lutein, which are constituted by hydrogen, carbon and oxygen. Carotenoids, as antioxidant compounds, assume a key role in the protection of cells. In fact, quenching of singlet oxygen, light capture and photosynthesis protection are the most relevant biological functions of carotenoids. The present review aims at describing (i the biological functions of carotenoids and their benefits for human health, (ii the most common carotenoids from marine organisms and (iii carotenoids having large success in pharmaceutical, nutraceutical and cosmeceutical industries, highlighting the scientific progress in marine species cultivation for natural pigments production.

  11. Functional knowledge transfer for high-accuracy prediction of under-studied biological processes.

    Directory of Open Access Journals (Sweden)

    Christopher Y Park

    Full Text Available A key challenge in genetics is identifying the functional roles of genes in pathways. Numerous functional genomics techniques (e.g. machine learning that predict protein function have been developed to address this question. These methods generally build from existing annotations of genes to pathways and thus are often unable to identify additional genes participating in processes that are not already well studied. Many of these processes are well studied in some organism, but not necessarily in an investigator's organism of interest. Sequence-based search methods (e.g. BLAST have been used to transfer such annotation information between organisms. We demonstrate that functional genomics can complement traditional sequence similarity to improve the transfer of gene annotations between organisms. Our method transfers annotations only when functionally appropriate as determined by genomic data and can be used with any prediction algorithm to combine transferred gene function knowledge with organism-specific high-throughput data to enable accurate function prediction. We show that diverse state-of-art machine learning algorithms leveraging functional knowledge transfer (FKT dramatically improve their accuracy in predicting gene-pathway membership, particularly for processes with little experimental knowledge in an organism. We also show that our method compares favorably to annotation transfer by sequence similarity. Next, we deploy FKT with state-of-the-art SVM classifier to predict novel genes to 11,000 biological processes across six diverse organisms and expand the coverage of accurate function predictions to processes that are often ignored because of a dearth of annotated genes in an organism. Finally, we perform in vivo experimental investigation in Danio rerio and confirm the regulatory role of our top predicted novel gene, wnt5b, in leftward cell migration during heart development. FKT is immediately applicable to many bioinformatics

  12. Engineering biomechanically functional neocartilage derived from expanded articular chondrocytes through the manipulation of cell-seeding density and dexamethasone concentration.

    Science.gov (United States)

    Huang, Brian J; Huey, Daniel J; Hu, Jerry C; Athanasiou, Kyriacos A

    2017-08-01

    Recent work has established methods to engineer self-assembled, scaffold-free neocartilage from an expanded articular chondrocyte (AC) cell source. In continuing such work, the objective of the present study was to investigate the effects of cell-seeding density and dexamethasone concentration on these neocartilage constructs. Neocartilage discs (5 mm diameter) were formed by self-assembling passaged leporine articular chondrocytes into non-adherent agarose moulds. The cell-seeding densities (2, 3, 4, 5 and 6 million cells/construct) and dexamethasone concentrations (10 and 100 nm) in the culture medium were varied in a full-factorial study. After 4 weeks, the neocartilage constructs were assessed for morphological, biochemical and biomechanical properties. The cell-seeding density profoundly affected neocartilage properties. The two dexamethasone concentrations explored did not induce overall significant differences. Constructs formed using lower cell-seeding densities possessed much higher biochemical and biomechanical properties than constructs seeded with higher cell densities. Notably, the 2 million cells/construct group formed hyaline-like neocartilage with a collagen wet weight (WW) content of ~7% and a Young's modulus of ~4 MPa, representing the high end of values achieved in self-assembled neocartilage. Excitingly, the mechanical properties of these constructs were on a par with that of native cartilage tissues tested under similar conditions. Through optimization of cell-seeding density, this study shows for the first time the use of expanded ACs to form homogeneous self-assembled neocartilage with exceptionally high tensile strength. With such functional properties, these engineered neocartilage constructs provide a promising alternative for treating articular lesions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Expanding Pseudorandom Functions

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre; Nielsen, Jesper Buus

    2002-01-01

    used) encryption modes as CBC mode and counter (CTR) mode, but is provably secure against chosen-plaintext attack (CPA) already if the underlying symmetric cipher is secure against known-plaintext attack (KPA). We prove that CBC, CTR and Jutla’s integrity aware modes do not have this property....... In particular, we prove that when using a KPA secure block cipher, then: CBC mode is KPA secure, but need not be CPA secure, Jutla’s modes need not be CPA secure, and CTR mode need not be even KPA secure. The analysis is done in a concrete security framework....

  14. DMPD: Type I interferon receptors: biochemistry and biological functions. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17502368 Type I interferon receptors: biochemistry and biological functions. de Wee...(.html) (.csml) Show Type I interferon receptors: biochemistry and biological functions. PubmedID 17502368 T...itle Type I interferon receptors: biochemistry and biological functions. Authors

  15. Evaluation of the grand-canonical partition function using expanded Wang-Landau simulations. III. Impact of combining rules on mixtures properties

    Energy Technology Data Exchange (ETDEWEB)

    Desgranges, Caroline; Delhommelle, Jerome [Department of Chemistry, University of North Dakota, 151 Cornell Street Stop 9024, Grand Forks, North Dakota 58202 (United States)

    2014-03-14

    Combining rules, such as the Lorentz-Berthelot rules, are routinely used to calculate the thermodynamic properties of mixtures using molecular simulations. Here we extend the expanded Wang-Landau simulation approach to determine the impact of the combining rules on the value of the partition function of binary systems, and, in turn, on the phase coexistence and thermodynamics of these mixtures. We study various types of mixtures, ranging from systems of rare gases to biologically and technologically relevant mixtures, such as water-urea and water-carbon dioxide. Comparing the simulation results to the experimental data on mixtures of rare gases allows us to rank the performance of combining rules. We find that the widely used Lorentz-Berthelot rules exhibit the largest deviations from the experimental data, both for the bulk and at coexistence, while the Kong and Waldman-Hagler provide much better alternatives. In particular, in the case of aqueous solutions of urea, we show that the use of the Lorentz-Berthelot rules has a strong impact on the Gibbs free energy of the solute, overshooting the value predicted by the Waldman-Hagler rules by 7%. This result emphasizes the importance of the combining rule for the determination of hydration free energies using molecular simulations.

  16. Evaluation of the grand-canonical partition function using expanded Wang-Landau simulations. III. Impact of combining rules on mixtures properties

    Science.gov (United States)

    Desgranges, Caroline; Delhommelle, Jerome

    2014-03-01

    Combining rules, such as the Lorentz-Berthelot rules, are routinely used to calculate the thermodynamic properties of mixtures using molecular simulations. Here we extend the expanded Wang-Landau simulation approach to determine the impact of the combining rules on the value of the partition function of binary systems, and, in turn, on the phase coexistence and thermodynamics of these mixtures. We study various types of mixtures, ranging from systems of rare gases to biologically and technologically relevant mixtures, such as water-urea and water-carbon dioxide. Comparing the simulation results to the experimental data on mixtures of rare gases allows us to rank the performance of combining rules. We find that the widely used Lorentz-Berthelot rules exhibit the largest deviations from the experimental data, both for the bulk and at coexistence, while the Kong and Waldman-Hagler provide much better alternatives. In particular, in the case of aqueous solutions of urea, we show that the use of the Lorentz-Berthelot rules has a strong impact on the Gibbs free energy of the solute, overshooting the value predicted by the Waldman-Hagler rules by 7%. This result emphasizes the importance of the combining rule for the determination of hydration free energies using molecular simulations.

  17. Click Chemistry Mediated Functionalization of Vertical Nanowires for Biological Applications.

    Science.gov (United States)

    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.

  18. Discoveries of rhythms in human biological functions: a historical review.

    Science.gov (United States)

    Lemmer, Björn

    2009-08-01

    Though there are very early and ancient observations on the daily variation in physiological and pathophysiological functions (e.g., bronchial asthma), more detailed and scientific reports were not published until the beginning of the 17th century. The aim of this review is to bring those reports to the attention of researchers of chronobiology and chronopharmacology. The ancient books and their contents, which constitute the basis for this review, are part of the personal library collection of the author; numerous observations and reports on biologic rhythms in man are presented here for the first time. The intent of this review is to demonstrate that the fields of chronobiology and chronopharmacology are not only a new and modern branch of science, but that it stands on the shoulders of wonderful and insightful observations and explanations made by our scientific forefathers. It is the hope that the reader will enjoy the richness of the ancient reports that contribute to our present knowledge achieved through astute early biologic rhythm research.

  19. Biologically functionalized nanochannels on ferroelectric lead zirconium titanate surfaces.

    Energy Technology Data Exchange (ETDEWEB)

    Ocola, L. E.; Pan, W. C.; Kuo, M.; Tirumala, V. R.; Reiss, B. D.; Firestone, M. A.; Illinois Mathematics and Science Academy

    2005-01-01

    We recently started a program at Argonne to exploit patterned, polarizable ferroelectric surfaces, such as lead zirconium titanate (PZT), as a means to create field-responsive inorganic-biomolecule interfaces to study and manipulate biomatter on surfaces. In this paper we will discuss the integration of nanochannels on the surface of PZT films and their selective functionalization to create nanovalves to control nanofluidic flow. Microfluidic devices have been fabricated using a variety of methods, ranging from thermal decomposition of buried patterned channels, to fabricating trenches via plasma etch or hot embossing followed by trench capping. Our work focuses on an alternative method by using a bilayer resist in an inverted configuration normally used for T- and Gamma- gate fabrication. This method is capable of yielding sub-100 nm nanochannels with high aspect ratios and sub-500nm alignment. We have recently demonstrated that the polarization hysteresis loop of PZT is the same before and after exposure to an aqueous environment. This opens the possibility of selective surface modification of PZT via coupling of a wide range of biomolecules (e.g., peptides, proteins) and the use of the electric-field-responsive properties of PZT to manipulate the function (e.g., orientation) of the tethered biomolecules. We have used phage display techniques to evolve specific peptide motifs that selectively bind to PZT. The optimum heptapeptide that facilitates both the attachment of functional biological molecules to the surface of PZT has been identified.

  20. The biology of 5-lipoxygenase: function, structure, and regulatory mechanisms.

    Science.gov (United States)

    Silverman, E S; Drazen, J M

    1999-01-01

    5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid to leukotriene A4 (LTA4). The first step consists of the oxidation of arachidonic acid to the unstable intermediate 5-hydroperoxyeicosatetraenoic acid (5-HPETE), and the second step is the dehydration of 5-HPETE to form LTA4. These events are the first committed reactions leading to the synthesis of all leukotrienes and play a critical role in controlling leukotriene production. 5-LO has evolved many complex structural features and regulatory mechanisms to allow it to fulfill this highly specialized role. The biology of 5-LO is reviewed here with an emphasis on enzymatic function, protein and gene structure, essential cofactors, and the many regulatory mechanisms controlling its expression.

  1. Structure, Function, and Biology of the Enterococcus faecalis Cytolysin

    Directory of Open Access Journals (Sweden)

    Daria Van Tyne

    2013-04-01

    Full Text Available Enterococcus faecalis is a Gram-positive commensal member of the gut microbiota of a wide range of organisms. With the advent of antibiotic therapy, it has emerged as a multidrug resistant, hospital-acquired pathogen. Highly virulent strains of E. faecalis express a pore-forming exotoxin, called cytolysin, which lyses both bacterial and eukaryotic cells in response to quorum signals. Originally described in the 1930s, the cytolysin is a member of a large class of lanthionine-containing bacteriocins produced by Gram-positive bacteria. While the cytolysin shares some core features with other lantibiotics, it possesses unique characteristics as well. The current understanding of cytolysin biosynthesis, structure/function relationships, and contribution to the biology of E. faecalis are reviewed, and opportunities for using emerging technologies to advance this understanding are discussed.

  2. Biological activity of lactoferrin-functionalized biomimetic hydroxyapatite nanocrystals.

    Science.gov (United States)

    Nocerino, Nunzia; Fulgione, Andrea; Iannaccone, Marco; Tomasetta, Laura; Ianniello, Flora; Martora, Francesca; Lelli, Marco; Roveri, Norberto; Capuano, Federico; Capparelli, Rosanna

    2014-01-01

    The emergence of bacterial strains resistant to antibiotics is a general public health problem. Progress in developing new molecules with antimicrobial properties has been made. In this study, we evaluated the biological activity of a hybrid nanocomposite composed of synthetic biomimetic hydroxyapatite surface-functionalized by lactoferrin (LF-HA). We evaluated the antimicrobial, anti-inflammatory, and antioxidant properties of LF-HA and found that the composite was active against both Gram-positive and Gram-negative bacteria, and that it modulated proinflammatory and anti-inflammatory responses and enhanced antioxidant properties as compared with LF alone. These results indicate the possibility of using LF-HA as an antimicrobial system and biomimetic hydroxyapatite as a candidate for innovative biomedical applications.

  3. Biological Functional Relevance of Asymmetric Dimethylarginine (ADMA in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Sara Franceschelli

    2013-12-01

    Full Text Available There is growing evidence that increased levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA may contribute to endothelial dysfunction. Studies in animal models as well as in humans have suggested that the increase in ADMA occurs at a time when vascular disease has not yet become clinically evident. ADMA competitively inhibits NO elaboration by displacing L-arginine from NO synthase. In a concentration-dependent manner, it thereby interferes not only with endothelium-dependent, NO-mediated vasodilation, but also with other biological functions exerted by NO. The upshot may be a pro-atherogenic state. Recently, several studies have investigated the effect of various therapeutical interventions on ADMA plasma concentrations.

  4. Non-coding RNAs: biological functions and applications.

    Science.gov (United States)

    Santosh, Baby; Varshney, Akhil; Yadava, Pramod Kumar

    2015-01-01

    Analyses of the international human genome sequencing results in 2004 converged to a consensual number of ~20,000 protein-coding genes, spanning over explosion of research addressing possible functional roles for the other 98% of the human genome that does not encode proteins. In fact, >90% of the human genome is likely to be transcribed yielding a complex network of overlapping transcripts that include tens of thousands of long RNAs with little or no protein forming capacity; they are collectively called non-coding RNA. This review highlights the fundamental concepts of biological roles of non-coding RNA and their importance in regulation of cellular physiology under disease conditions like cancer. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Functional genomics and structural biology in the definition of gene function.

    Science.gov (United States)

    Hrmova, Maria; Fincher, Geoffrey B

    2009-01-01

    By mid-2007, the three-dimensional (3D) structures of some 45,000 proteins have been solved, over a period where the linear structures of millions of genes have been defined. Technical challenges associated with X-ray crystallography are being overcome and high-throughput methods both for crystallization of proteins and for solving their 3D structures are under development. The question arises as to how structural biology can be integrated with and adds value to functional genomics programs. Structural biology will assist in the definition of gene function through the identification of the likely function of the protein products of genes. The 3D information allows protein sequences predicted from DNA sequences to be classified into broad groups, according to the overall 'fold', or 3D shape, of the protein. Structural information can be used to predict the preferred substrate of a protein, and thereby greatly enhance the accurate annotation of the corresponding gene. Furthermore, it will enable the effects of amino acid substitutions in enzymes to be better understood with respect to enzyme function and could thereby provide insights into natural variation in genes. If the molecular basis of transcription factor-DNA interactions were defined through precise 3D knowledge of the protein-DNA binding site, it would be possible to predict the effects of base substitutions within the motif on the specificity and/or kinetics of binding. In this chapter, we present specific examples of how structural biology can provide valuable information for functional genomics programs.

  6. Functionalized nanoparticles for biological imaging and detection applications

    Science.gov (United States)

    Mei, Bing C.

    Semiconductor quantum dots (QDs) and gold nanoparticles (AuNPs) have gained tremendous attention in the last decade as a result of their size-dependent spectroscopic properties. These nanoparticles have been a subject of intense study to bridge the gap between macroscopic and atomic behavior, as well as to generate new materials for novel applications in therapeutics, biological sensing, light emitting devices, microelectronics, lasers, and solar cells. One of the most promising areas for the use of these nanoparticles is in biotechnology, where their size-dependent optical properties are harnessed for imaging and sensing applications. However, these nanoparticles, as synthesized, are often not stable in aqueous media and lack simple and reliable means of covalently linking to biomolecules. The focus of this work is to advance the progress of these nanomaterials for biotechnology by synthesizing them, characterizing their optical properties and rendering them water-soluble and functional while maintaining their coveted optical properties. QDs were synthesized by an organometallic chemical procedure that utilizes coordinating solvents to provide brightly luminescent nanoparticles. The optical interactions of these QDs were studied as a function of concentration to identify particle size-dependent optimal concentrations, where scattering and indirection excitation are minimized and the amount light observed per particle is maximized. Both QDs and AuNPs were rendered water-soluble and stable in a broad range of biologically relevant conditions by using a series of ligands composed of dihydrolipoic acid (DHLA) appended to poly(ethylene glycol) methyl ether. By studying the stability of the surface modified AuNPs, we revealed some interesting information regarding the role of the surface ligand on the nanoparticle stability (i.e. solubility in high salt concentration, resistance to dithiothreitol competition and cyanide decomposition). Furthermore, the nanoparticles

  7. Biosynthesis and biological functions of terpenoids in plants.

    Science.gov (United States)

    Tholl, Dorothea

    2015-01-01

    Terpenoids (isoprenoids) represent the largest and most diverse class of chemicals among the myriad compounds produced by plants. Plants employ terpenoid metabolites for a variety of basic functions in growth and development but use the majority of terpenoids for more specialized chemical interactions and protection in the abiotic and biotic environment. Traditionally, plant-based terpenoids have been used by humans in the food, pharmaceutical, and chemical industries, and more recently have been exploited in the development of biofuel products. Genomic resources and emerging tools in synthetic biology facilitate the metabolic engineering of high-value terpenoid products in plants and microbes. Moreover, the ecological importance of terpenoids has gained increased attention to develop strategies for sustainable pest control and abiotic stress protection. Together, these efforts require a continuous growth in knowledge of the complex metabolic and molecular regulatory networks in terpenoid biosynthesis. This chapter gives an overview and highlights recent advances in our understanding of the organization, regulation, and diversification of core and specialized terpenoid metabolic pathways, and addresses the most important functions of volatile and nonvolatile terpenoid specialized metabolites in plants.

  8. Glowing Worms: Biological, Chemical, and Functional Diversity of Bioluminescent Annelids.

    Science.gov (United States)

    Verdes, Aida; Gruber, David F

    2017-07-01

    Bioluminescence, the ability to produce light by living organisms, has evolved independently in numerous lineages across the tree of life. Luminous forms are found in a wide range of taxonomic groups from bacteria to vertebrates, although the great majority of bioluminescent organisms are marine taxa. Within the phylum Annelida, bioluminescence is widespread, present in at least 98 terrestrial and marine species that represent 45 genera distributed in thirteen lineages of clitellates and polychaetes. The ecological diversity of luminous annelids is unparalleled, with species occupying a great variety of habitats including both terrestrial and marine ecosystems, from coastal waters to the deep-sea, in benthic and pelagic habitats from polar to tropical regions. This great taxonomic and ecological diversity is matched by the wide array of bioluminescent colors-including yellow light, which is very rare among marine taxa-different emission wavelengths even between species of the same genus, and varying patterns, chemical reactions and kinetics. This diversity of bioluminescence colors and patterns suggests that light production in annelids might be involved in a variety of different functions, including defensive mechanisms like sacrificial lures or aposematic signals, and intraspecific communication systems. In this review, we explore the world of luminous annelids, particularly focusing on the current knowledge regarding their taxonomic and ecological diversity and discussing the putative functions and chemistries of their bioluminescent systems. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology 2017. This work is written by US Government employees and is in the public domain in the US.

  9. Functional and biological characteristics of asthma in cleaning workers.

    Science.gov (United States)

    Vizcaya, David; Mirabelli, Maria C; Orriols, Ramon; Antó, Josep Maria; Barreiro, Esther; Burgos, Felip; Arjona, Lourdes; Gomez, Federico; Zock, Jan-Paul

    2013-05-01

    Cleaning workers have an increased risk of asthma but the underlying mechanisms are largely unknown. We studied functional and biological characteristics in asthmatic cleaners and compared these to healthy cleaners. Forty-two cleaners with a history of asthma and/or recent respiratory symptoms and 53 symptom-free controls were identified. Fractional exhaled nitric oxide (FeNO) was measured and forced spirometry with reversibility testing was performed. Total IgE, pulmonary surfactant protein D and the 16 kDa Clara Cell secretory protein were measured in blood serum. Interleukins and other cytokines, growth factors, cys-leukotrienes and 8-isoprostane were measured in exhaled breath condensate. Information on occupational and domestic use of cleaning products was obtained in an interview. Associations between asthma status, specific characteristics and the use of cleaning products were evaluated using multivariable linear and logistic regression analyses. Asthma was associated with an 8% (95% confidence interval (CI) 1-15%) lower postbronchodilator FEV1, a higher prevalence of atopy (42% vs. 10%) and a 2.9 (CI 1.5-5.6) times higher level of total IgE. Asthma status was not associated with the other respiratory biomarkers. Most irritant products and sprays were more often used by asthmatic cleaners. The use of multiuse products, glass cleaners and polishes at work was associated with higher FeNO, particularly in controls. Asthma in cleaning workers is characterised by non-reversible lung function decrement and increased total IgE. Oxidative stress, altered lung permeability and eosinophilic inflammation are unlikely to play an important underlying role, although the latter may be affected by certain irritant cleaning exposures. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Functional synchronization of biological rhythms in a tritrophic system.

    Directory of Open Access Journals (Sweden)

    Sufang Zhang

    Full Text Available In a tritrophic system formed by a plant, an herbivore and a natural enemy, each component has its own biological rhythm. However, the rhythm correlations among the three levels and the underlying mechanisms in any tritrophic system are largely unknown. Here, we report that the rhythms exhibited bidirectional correlations in a model tritrophic system involving a lima bean, a pea leafminer and a parasitoid. From the bottom-up perspective, the rhythm was initiated from herbivore feeding, which triggered the rhythms of volatile emissions; then the rhythmic pattern of parasitoid activities was affected, and these rhythms were synchronized by a light switch signal. Increased volatile concentration can enhance the intensity of parasitoid locomotion and oviposition only under light. From the top-down perspective, naive and oviposition-experienced parasitoids were able to utilize the different volatile rhythm information from the damaged plant to locate host leafminers respectively. Our results indicated that the three interacting organisms in this system can achieve rhythmic functional synchronization under a natural light-dark photoperiod, but not under constant light or darkness. These findings provide new insight into the rhythm synchronization of three key players that contribute to the utilization of light and chemical signals, and our results may be used as potential approaches for manipulating natural enemies.

  11. hCG: Biological Functions and Clinical Applications.

    Science.gov (United States)

    Nwabuobi, Chinedu; Arlier, Sefa; Schatz, Frederick; Guzeloglu-Kayisli, Ozlem; Lockwood, Charles Joseph; Kayisli, Umit Ali

    2017-09-22

    Human chorionic gonadotropin (hCG) is produced primarily by differentiated syncytiotrophoblasts, and represents a key embryonic signal that is essential for the maintenance of pregnancy. hCG can activate various signaling cascades including mothers against decapentaplegic homolog 2 (Smad2), protein kinase C (PKC), and/or protein kinase A (PKA) in several cells types by binding to luteinizing hormone/chorionic gonadotropin receptor (LHCGR) or potentially by direct/indirect interaction with transforming growth factor beta receptor (TGFβR). The molecule displays specialized roles in promoting angiogenesis in the uterine endothelium, maintaining myometrial quiescence, as well as fostering immunomodulation at the maternal-fetal interface. It is a member of the glycoprotein hormone family that includes luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH). The α-subunit of hCG displays homologies with TSH, LH, and FSH, whereas the β subunit is 80-85% homologous to LH. The hCG molecule is produced by a variety of organs, exists in various forms, exerts vital biological functions, and has various clinical roles ranging from diagnosis and monitoring of pregnancy and pregnancy-related disorders to cancer surveillance. This review presents a detailed examination of hCG and its various clinical applications.

  12. hCG: Biological Functions and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Chinedu Nwabuobi

    2017-09-01

    Full Text Available Human chorionic gonadotropin (hCG is produced primarily by differentiated syncytiotrophoblasts, and represents a key embryonic signal that is essential for the maintenance of pregnancy. hCG can activate various signaling cascades including mothers against decapentaplegic homolog 2 (Smad2, protein kinase C (PKC, and/or protein kinase A (PKA in several cells types by binding to luteinizing hormone/chorionic gonadotropin receptor (LHCGR or potentially by direct/indirect interaction with transforming growth factor beta receptor (TGFβR. The molecule displays specialized roles in promoting angiogenesis in the uterine endothelium, maintaining myometrial quiescence, as well as fostering immunomodulation at the maternal-fetal interface. It is a member of the glycoprotein hormone family that includes luteinizing hormone (LH, thyroid-stimulating hormone (TSH, and follicle-stimulating hormone (FSH. The α-subunit of hCG displays homologies with TSH, LH, and FSH, whereas the β subunit is 80–85% homologous to LH. The hCG molecule is produced by a variety of organs, exists in various forms, exerts vital biological functions, and has various clinical roles ranging from diagnosis and monitoring of pregnancy and pregnancy-related disorders to cancer surveillance. This review presents a detailed examination of hCG and its various clinical applications.

  13. Biological production of functional chemicals from renewable resources

    Energy Technology Data Exchange (ETDEWEB)

    Tokiwa, Y.; Calabia, B.P. [National Inst. of Advanced Industrial Science and Technology, Tsukuba (Japan)

    2008-06-15

    The biological conversion of biomass into commodity and specialty chemicals is gaining interest due to an increased awareness of the impacts of greenhouse gases (GHGs) on the environment. New processing techniques for renewable feedstocks must be developed in order to facilitate the shift from fossil fuels to renewable energy sources. This article reviewed developments for renewable feedstocks for the production of multifunctional chemicals. Biotechnological methods of replacing chemical processes were outlined, including the fermentative production of lactic acid, as well as the production of bio-materials for use as monomers in plastics, lactic acid for polylactide (PLA), (R)-3-hydroxybutyric acid (R-3HB), poly(R)-3-hydroxybutyrate (PHB) and poly(butylene succinate) (PBS). Studies on lactic acid production and methods of developing effective substrates for biochemical production were reviewed along with mechanisms related to acid tolerance. The distribution of lactic acid bacteria (LAB) was discussed together with methods of increasing lactic acid concentrations. The article also reviewed species of microorganisms capable of producing significant amounts of functional chemicals. 54 refs., 2 tabs., 7 figs.

  14. Expanding subjectivities

    DEFF Research Database (Denmark)

    Lundgaard Andersen, Linda; Soldz, Stephen

    2012-01-01

    A major theme in recent psychoanalytic thinking concerns the use of therapist subjectivity, especially “countertransference,” in understanding patients. This thinking converges with and expands developments in qualitative research regarding the use of researcher subjectivity as a tool to understa...

  15. Expander Codes

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 10; Issue 1. Expander Codes - The Sipser–Spielman Construction. Priti Shankar. General Article Volume 10 ... Author Affiliations. Priti Shankar1. Department of Computer Science and Automation, Indian Institute of Science Bangalore 560 012, India.

  16. Phytochrome from Green Plants: Properties and biological Function

    Energy Technology Data Exchange (ETDEWEB)

    Quail, Peter H.

    2014-07-25

    Pfr conformer reverses this activity upon initial light exposure, inducing the switch to photomorphogenic development. This reversal involves light-triggered translocation of the photoactivated phy molecule into the nucleus where it interacts with PIF-family members, inducing rapid phosphorylation and degradation of the PIFs via the ubiquitin-proteasome system. This degradation in turn elicits rapid alterations in gene expression that drive the deetiolation transition. This project has made considerable progress in defining phy-PIF signaling activity in controlling the SAR. The biological functions of the multiple PIF-family members in controlling the SAR, including dissection of the relative contributions of the individual PIFs to this process, as well as to diurnal growth-control oscillations, have been investigated using higher-order pif-mutant combinations. Using microarray analysis of a quadruple pif mutant we have defined the shade-induced, PIF-regulated transcriptional network genome-wide. This has revealed that a dynamic antagonism between the phys and PIFs generates selective reciprocal responses during deetiolation and the SAR in a rapidly light-responsive transcriptional network. Using integrated RNA-seq and ChIP-seq analysis of higher order pif-mutant combinations, we have defined the direct gene-targets of PIF transcriptional regulation, and have obtained evidence that this regulation involves differential direct targeting of rapidly light-responsive genes by the individual PIF-family members. This project has provided significant advances in our understanding of the molecular mechanisms by which the phy-PIF photosensory signaling pathway regulates an important bioenergy-related plant response to the light environment. The identification of molecular targets in the primary transcriptional-regulatory circuitry of this pathway has the potential to enable genetic or reverse-genetic manipulation of the partitioning of carbon between reproductive and

  17. Partition expanders

    Czech Academy of Sciences Publication Activity Database

    Gavinsky, Dmitry; Pudlák, Pavel

    2017-01-01

    Roč. 60, č. 3 (2017), s. 378-395 ISSN 1432-4350 R&D Projects: GA ČR GBP202/12/G061 Institutional support: RVO:67985840 Keywords : expanders * pseudorandomness * communication complexity Subject RIV: BA - General Mathematics Impact factor: 0.645, year: 2016 http://link.springer.com/article/10.1007%2Fs00224-016-9738-5

  18. Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas.

    Directory of Open Access Journals (Sweden)

    Irina Haecker

    Full Text Available KSHV is the etiological agent of Kaposi's sarcoma (KS, primary effusion lymphoma (PEL, and a subset of multicentricCastleman's disease (MCD. The fact that KSHV-encoded miRNAs are readily detectable in all KSHV-associated tumors suggests a potential role in viral pathogenesis and tumorigenesis. MiRNA-mediated regulation of gene expression is a complex network with each miRNA having many potential targets, and to date only few KSHV miRNA targets have been experimentally determined. A detailed understanding of KSHV miRNA functions requires high-through putribonomics to globally analyze putative miRNA targets in a cell type-specific manner. We performed Ago HITS-CLIP to identify viral and cellular miRNAs and their cognate targets in two latently KSHV-infected PEL cell lines. Ago HITS-CLIP recovered 1170 and 950 cellular KSHV miRNA targets from BCBL-1 and BC-3, respectively. Importantly, enriched clusters contained KSHV miRNA seed matches in the 3'UTRs of numerous well characterized targets, among them THBS1, BACH1, and C/EBPβ. KSHV miRNA targets were strongly enriched for genes involved in multiple pathways central for KSHV biology, such as apoptosis, cell cycle regulation, lymphocyte proliferation, and immune evasion, thus further supporting a role in KSHV pathogenesis and potentially tumorigenesis. A limited number of viral transcripts were also enriched by HITS-CLIP including vIL-6 expressed only in a subset of PEL cells during latency. Interestingly, Ago HITS-CLIP revealed extremely high levels of Ago-associated KSHV miRNAs especially in BC-3 cells where more than 70% of all miRNAs are of viral origin. This suggests that in addition to seed match-specific targeting of cellular genes, KSHV miRNAs may also function by hijacking RISCs, thereby contributing to a global de-repression of cellular gene expression due to the loss of regulation by human miRNAs. In summary, we provide an extensive list of cellular and viral miRNA targets representing an

  19. Computing biological functions using BioΨ, a formal description of biological processes based on elementary bricks of actions

    Science.gov (United States)

    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

  20. The functional and biological properties of whey proteins: prospects for the development of functional foods

    Directory of Open Access Journals (Sweden)

    H. J. T. KORHONEN

    2008-12-01

    Full Text Available Advances in processing technologies and the accumulation of scientific data on the functional and biological properties of whey components have contributed to the growing commercial valuation of cheese whey over the last decade. New membrane separation and chromatographic techniques have made it possible to fractionate and enrich various components of whey more efficiently than before. The specific properties of these components can now be examined in greater detail and new applications developed accordingly. The utilisation of cheese whey is evolving into a new industry producing a multitude of purified ingredients for numerous purposes. The most significant areas of R&D related to whey proteins include functional foods, the rheological properties of foodstuffs, and biopharmaceuticals.

  1. Expanding versus non expanding universe

    CERN Document Server

    Alfonso-Faus, Antonio

    2012-01-01

    In cosmology the number of scientists using the framework of an expanding universe is very high. This model, the big-bang, is now overwhelmingly present in almost all aspects of society. It is the main stream cosmology of today. A small number of scientists are researching on the possibility of a non-expanding universe. The existence of these two groups, one very large and the other very small, is a good proof of the use of the scientific method: it does not drive to an absolute certainty. All models have to be permanently validated, falsified. Ockham's razor, a powerful philosophical tool, will probably change the amount of scientists working in each of these groups. We present here a model where a big-bang is unnecessary. It ends, in a finite time, in a second INFLATION, or a disaggregation to infinity. We also discuss the possibilities of a non-expanding universe model. Only a few references will be cited, mainly concerned with our own work in the past, thus purposely avoiding citing the many thousands of ...

  2. Click chemistry mediated functionalization of vertical nanowires for biological applications

    DEFF Research Database (Denmark)

    Vutti, Surendra; Schoffelen, Sanne; Bolinsson, Jessica

    2016-01-01

    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...... 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...

  3. Exploring candidate biological functions by Boolean Function Networks for Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Maria Simak

    Full Text Available The great amount of gene expression data has brought a big challenge for the discovery of Gene Regulatory Network (GRN. For network reconstruction and the investigation of regulatory relations, it is desirable to ensure directness of links between genes on a map, infer their directionality and explore candidate biological functions from high-throughput transcriptomic data. To address these problems, we introduce a Boolean Function Network (BFN model based on techniques of hidden Markov model (HMM, likelihood ratio test and Boolean logic functions. BFN consists of two consecutive tests to establish links between pairs of genes and check their directness. We evaluate the performance of BFN through the application to S. cerevisiae time course data. BFN produces regulatory relations which show consistency with succession of cell cycle phases. Furthermore, it also improves sensitivity and specificity when compared with alternative methods of genetic network reverse engineering. Moreover, we demonstrate that BFN can provide proper resolution for GO enrichment of gene sets. Finally, the Boolean functions discovered by BFN can provide useful insights for the identification of control mechanisms of regulatory processes, which is the special advantage of the proposed approach. In combination with low computational complexity, BFN can serve as an efficient screening tool to reconstruct genes relations on the whole genome level. In addition, the BFN approach is also feasible to a wide range of time course datasets.

  4. Oxidative metabolites of lycopene and their biological functions

    Science.gov (United States)

    To gain a better understanding of the beneficial biological activities of lycopene on cancer prevention, a greater knowledge of the metabolism of lycopene is needed. In particular, the identification of lycopene metabolites and oxidation products in vivo; the importance of tissue specific lycopene c...

  5. GENIUS: web server to predict local gene networks and key genes for biological functions.

    Science.gov (United States)

    Puelma, Tomas; Araus, Viviana; Canales, Javier; Vidal, Elena A; Cabello, Juan M; Soto, Alvaro; Gutiérrez, Rodrigo A

    2017-03-01

    GENIUS is a user-friendly web server that uses a novel machine learning algorithm to infer functional gene networks focused on specific genes and experimental conditions that are relevant to biological functions of interest. These functions may have different levels of complexity, from specific biological processes to complex traits that involve several interacting processes. GENIUS also enriches the network with new genes related to the biological function of interest, with accuracies comparable to highly discriminative Support Vector Machine methods. GENIUS currently supports eight model organisms and is freely available for public use at http://networks.bio.puc.cl/genius . genius.psbl@gmail.com. Supplementary data are available at Bioinformatics online.

  6. Cerenkov Radiation: A Multi-functional Approach for Biological Sciences

    Science.gov (United States)

    Ma, Xiaowei; Wang, Jing; Cheng, Zhen

    2014-02-01

    Cerenkov radiation (CR) has been used in various biological research fields, which has aroused lots of attention in recent years. Combining optical imaging instruments and most of nuclear medicine imaging or radiotherapy probes, the CR was developed as a new imaging modality for biology studies, called Cerenkov luminescence imaging (CLI). On the other hand, it was novelly used as an internal excitation source to activate some fluorophores for energy transfer imaging. However, it also has some shortages such as relatively weak luminescence intensity and low penetration in tissue. Thus some scientific groups demonstrated to optimize the CLI and demonstrated it to three-dimension tomography. In this article, we elaborate on its principle, history, and applications and discuss a number of directions for technical improvements. Then concluded some advantages and shortages of CR and discuss some prospects of it.

  7. Recent Advances in Momordica charantia: Functional Components and Biological Activities

    Directory of Open Access Journals (Sweden)

    Shuo Jia

    2017-11-01

    Full Text Available Momordica charantia L. (M. charantia, a member of the Cucurbitaceae family, is widely distributed in tropical and subtropical regions of the world. It has been used in folk medicine for the treatment of diabetes mellitus, and its fruit has been used as a vegetable for thousands of years. Phytochemicals including proteins, polysaccharides, flavonoids, triterpenes, saponins, ascorbic acid and steroids have been found in this plant. Various biological activities of M. charantia have been reported, such as antihyperglycemic, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer and anti-inflammatory activities. However, both in vitro and in vivo studies have also demonstrated that M. charantia may also exert toxic or adverse effects under different conditions. This review addresses the chemical constituents of M. charantia and discusses their pharmacological activities as well as their adverse effects, aimed at providing a comprehensive overview of the phytochemistry and biological activities of M. charantia.

  8. Expanded Dengue.

    Science.gov (United States)

    Kadam, D B; Salvi, Sonali; Chandanwale, Ajay

    2016-07-01

    The World Health Organization (WHO) has coined the term expanded dengue to describe cases which do not fall into either dengue shock syndrome or dengue hemorrhagic fever. This has incorporated several atypical findings of dengue. Dengue virus has not been enlisted as a common etiological agent in several conditions like encephalitis, Guillain Barre syndrome. Moreover it is a great mimic of co-existing epidemics like Malaria, Chikungunya and Zika virus disease, which are also mosquito-borne diseases. The atypical manifestations noted in dengue can be mutisystemic and multifacetal. In clinical practice, the occurrence of atypical presentation should prompt us to investigate for dengue. Knowledge of expanded dengue helps to clinch the diagnosis of dengue early, especially during ongoing epidemics, avoiding further battery of investigations. Dengue has proved to be the epidemic with the ability to recur and has a diverse array of presentation as seen in large series from India, Srilanka, Indonesia and Taiwan. WHO has given the case definition of dengue fever in their comprehensive guidelines. Accordingly, a probable case is defined as acute febrile illness with two or more of any findings viz. headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, leucopenia and supportive serology. There have been cases of patients admitted with fever, altered mentation with or without neck stiffness and pyramidal tract signs. Some had seizures or status epilepticus as presentation. When they were tested for serology, dengue was positive. After ruling out other causes, dengue remained the only culprit. We have come across varied presentations of dengue fever in clinical practice and the present article throws light on atypical manifestations of dengue. © Journal of the Association of Physicians of India 2011.

  9. Adipokines: biological functions and metabolically healthy obese profile

    OpenAIRE

    Pereira,Solange; Alvarez-Leite,Jacqueline

    2014-01-01

    Solange Silveira Pereira,1,2 Jacqueline I Alvarez-Leite1,21Laboratory for Atherosclerosis and Nutritional Biochemistry, Department of Biochemistry and Immunology, Institute of Biological Sciences, 2Alfa Institute of Gastroenterology, Clinics Hospital, Medicine School, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, BrazilAbstract: Adipose tissue is an extremely active organ, and plays a fundamental role in the genesis of comorbidities associated with obesity. Since the discover...

  10. Statistically advanced, self-similar, radial probability density functions of atmospheric and under-expanded hydrogen jets

    Science.gov (United States)

    Ruggles, Adam J.

    2015-11-01

    This paper presents improved statistical insight regarding the self-similar scalar mixing process of atmospheric hydrogen jets and the downstream region of under-expanded hydrogen jets. Quantitative planar laser Rayleigh scattering imaging is used to probe both jets. The self-similarity of statistical moments up to the sixth order (beyond the literature established second order) is documented in both cases. This is achieved using a novel self-similar normalization method that facilitated a degree of statistical convergence that is typically limited to continuous, point-based measurements. This demonstrates that image-based measurements of a limited number of samples can be used for self-similar scalar mixing studies. Both jets exhibit the same radial trends of these moments demonstrating that advanced atmospheric self-similarity can be applied in the analysis of under-expanded jets. Self-similar histograms away from the centerline are shown to be the combination of two distributions. The first is attributed to turbulent mixing. The second, a symmetric Poisson-type distribution centered on zero mass fraction, progressively becomes the dominant and eventually sole distribution at the edge of the jet. This distribution is attributed to shot noise-affected pure air measurements, rather than a diffusive superlayer at the jet boundary. This conclusion is reached after a rigorous measurement uncertainty analysis and inspection of pure air data collected with each hydrogen data set. A threshold based upon the measurement noise analysis is used to separate the turbulent and pure air data, and thusly estimate intermittency. Beta-distributions (four parameters) are used to accurately represent the turbulent distribution moments. This combination of measured intermittency and four-parameter beta-distributions constitutes a new, simple approach to model scalar mixing. Comparisons between global moments from the data and moments calculated using the proposed model show excellent

  11. An overview of the applicability of functional diversity in Biological Conservation

    OpenAIRE

    Freitas, J. R.; Mantovani, W.

    2017-01-01

    Abstract Functional diversity is increasingly pointed as a useful approach to reach Biological Conservation goals. Here, we provide an overview of the functional diversity approach status in the Biological Conservation field. We sought for peer-reviewed papers published over a period of twenty years (from 1994 to 2014). First we used the general topic “functional diversity” and then refined our search using the key-word “conservation”. We have identified the conservation strategies addressed,...

  12. Inferring biological functions of guanylyl cyclases with computational methods

    KAUST Repository

    Alquraishi, May Majed

    2013-09-03

    A number of studies have shown that functionally related genes are often co-expressed and that computational based co-expression analysis can be used to accurately identify functional relationships between genes and by inference, their encoded proteins. Here we describe how a computational based co-expression analysis can be used to link the function of a specific gene of interest to a defined cellular response. Using a worked example we demonstrate how this methodology is used to link the function of the Arabidopsis Wall-Associated Kinase-Like 10 gene, which encodes a functional guanylyl cyclase, to host responses to pathogens. © Springer Science+Business Media New York 2013.

  13. Mining Functional Modules in Heterogeneous Biological Networks Using Multiplex PageRank Approach.

    Science.gov (United States)

    Li, Jun; Zhao, Patrick X

    2016-01-01

    Identification of functional modules/sub-networks in large-scale biological networks is one of the important research challenges in current bioinformatics and systems biology. Approaches have been developed to identify functional modules in single-class biological networks; however, methods for systematically and interactively mining multiple classes of heterogeneous biological networks are lacking. In this paper, we present a novel algorithm (called mPageRank) that utilizes the Multiplex PageRank approach to mine functional modules from two classes of biological networks. We demonstrate the capabilities of our approach by successfully mining functional biological modules through integrating expression-based gene-gene association networks and protein-protein interaction networks. We first compared the performance of our method with that of other methods using simulated data. We then applied our method to identify the cell division cycle related functional module and plant signaling defense-related functional module in the model plant Arabidopsis thaliana. Our results demonstrated that the mPageRank method is effective for mining sub-networks in both expression-based gene-gene association networks and protein-protein interaction networks, and has the potential to be adapted for the discovery of functional modules/sub-networks in other heterogeneous biological networks. The mPageRank executable program, source code, the datasets and results of the presented two case studies are publicly and freely available at http://plantgrn.noble.org/MPageRank/.

  14. Plant Biology: Rethinking Structure-Function Relationships in Guard Cells.

    Science.gov (United States)

    Dow, Graham

    2017-10-09

    Recent findings highlight the role of polar reinforcement in guard cell function, which simultaneously improves our understanding of stomatal mechanics and questions our long-standing beliefs about structurally important factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. The lectins: properties, functions, and applications in biology and medicine

    National Research Council Canada - National Science Library

    Liener, Irvin E; Sharon, Nathan; Goldstein, Irwin J

    1986-01-01

    ... (Editors). The Enzymology of Post-Translational Modification of Proteins, Volume 1, 1980. Volume 2, 1985 W A I YIU CHEUNG (Editor). Calcium and Cell Function, Volume I: Calmodulin, 1980. Volume II, ...

  16. Functional response of Xylocoris falvipes , a biological control agent ...

    African Journals Online (AJOL)

    The warehouse pirate bug Xylocoris falvipes is an opportunist predator of many stored product insect pests. Its functional response in relationship with variable densities of prey appears as the Holling\\'s type II model. The predator X. falvipes, collected within small holder granaries in Mayo Danay division in the far North ...

  17. Measuring the functional redundancy of biological communities: a quantitative guide

    Czech Academy of Sciences Publication Activity Database

    Ricotta, C.; de Bello, Francesco; Moretti, M.; Caccianiga, M.; Cerabolini, B. E. L.; Pavoine, S.

    2016-01-01

    Roč. 7, č. 11 (2016), s. 1386-1395 ISSN 2041-210X Institutional support: RVO:67985939 Keywords : absolute vs. relative measures * community structure * functional uniqueness Subject RIV: EH - Ecology, Behaviour Impact factor: 5.708, year: 2016

  18. Structure, biological functions and applications of the AB5 toxins.

    Science.gov (United States)

    Beddoe, Travis; Paton, Adrienne W; Le Nours, Jérôme; Rossjohn, Jamie; Paton, James C

    2010-07-01

    AB(5) toxins are important virulence factors for several major bacterial pathogens, including Bordetella pertussis, Vibrio cholerae, Shigella dysenteriae and at least two distinct pathotypes of Escherichia coli. The AB(5) toxins are so named because they comprise a catalytic A-subunit, which is responsible for disruption of essential host functions, and a pentameric B-subunit that binds to specific glycan receptors on the target cell surface. The molecular mechanisms by which the AB(5) toxins cause disease have been largely unravelled, including recent insights into a novel AB(5) toxin family, subtilase cytotoxin (SubAB). Furthermore, AB(5) toxins have become a valuable tool for studying fundamental cellular functions, and are now being investigated for potential applications in the clinical treatment of human diseases. Copyright 2010 Elsevier Ltd. All rights reserved.

  19. The biology and function of exosomes in cancer

    OpenAIRE

    Kalluri, Raghu

    2016-01-01

    Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40?150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathway...

  20. Production and biological function of volatile esters in Saccharomyces cerevisiae

    OpenAIRE

    Saerens, Sofie M. G.; Delvaux, Freddy R; Verstrepen, Kevin J; Thevelein, Johan?M.

    2010-01-01

    Summary The need to understand and control ester synthesis is driven by the fact that esters play a key role in the sensorial quality of fermented alcoholic beverages like beer, wine and sake. As esters are synthesized in yeast via several complex metabolic pathways, there is a need to gain a clear understanding of ester metabolism and its regulation. The individual genes involved, their functions and regulatory mechanisms have to be identified. In alcoholic beverages, there are two important...

  1. Biological factors of natural and artificial ecosystems stable (unstable) functioning

    Science.gov (United States)

    Pechurkin, Nikolai S.

    The problem of sustainable development of humanity on Earth and the problem of supporting human life in space have the same scientific and methodological bases. The key to solve both problems is a long term maintenance of balanced material cycle. As a whole, natural or artificial ecosystems are to be more closed than open, but their elements (links of systems) are to be substantially open in interactions with each other. Prolonged stable interactions of different links have to have unique joint results - closed material cycling or biotic turnover. It is necessary to include, at least, three types of main links into any system to support real material cycling: producers, consumers, reducers. Producer links are now under studies in many laboratories. It is evident that the higher productivity of link, the lower link stability. Especially, it concerns with parasite impact to plants. As usual, artificial ecosystems are more simple (incomplete) than natural ecosystems, sometimes, they have not enough links for prolonged stable functioning. For example, life support system for space flight can be incomplete in consumer link, having only some crew persons, instead of interacting populations of consumers. As for reducer link, it is necessary to "organize" a special coordinated work of microbial biocenoses to fulfill proper cycling. Possible evolution of links, their self development is a matter of special attention for the maintenance of prolonged stable functioning. It's the most danger for systems with populations of quickly reproducing, so-called, R - strategists, according to symbols of logistic equation. From another side, quick reproduction of R - strategists is able to increase artificial ecosystems and their links functioning. After some damages of system, R - strategist's link can be quickly "self repaired" up to level of normal functioning. Some experimental data of this kind and mathematical models are to be discussed in the paper. This work is supported by

  2. Functional nanostructured platforms for chemical and biological sensing

    Science.gov (United States)

    Létant, S. E.

    2006-05-01

    The central goal of our work is to combine semiconductor nanotechnology and surface functionalization in order to build platforms for the selective detection of bio-organisms ranging in size from bacteria (micron range) down to viruses, as well as for the detection of chemical agents (nanometer range). We will show on three porous silicon platforms how pore geometry and pore wall chemistry can be combined and optimized to capture and detect specific targets. We developed a synthetic route allowing to directly anchor proteins on silicon surfaces and illustrated the relevance of this technique by immobilizing live enzymes onto electrochemically etched luminescent nano-porous silicon. The powerful association of the specific enzymes with the transducing matrix led to a selective hybrid platform for chemical sensing. We also used light-assisted electrochemistry to produce periodic arrays of through pores on pre-patterned silicon membranes with controlled diameters ranging from many microns down to tens of nanometers. We demonstrated the first covalently functionalized silicon membranes and illustrated their selective capture abilities with antibody-coated micro-beads. These engineered membranes are extremely versatile and could be adapted to specifically recognize the external fingerprints (size and coat composition) of target bio-organisms. Finally, we fabricated locally functionalized single nanopores using a combination of focused ion beam drilling and ion beam assisted oxide deposition. We showed how a silicon oxide ring can be grown around a single nanopore and how it can be functionalized with DNA probes to detect single viral-sized beads. The next step for this platform is the detection of whole viruses and bacteria.

  3. Review article: the expanding role of biological agents in the treatment of inflammatory bowel disease - focus on selective adhesion molecule inhibition

    NARCIS (Netherlands)

    Rutgeerts, P.; van Deventer, S.; Schreiber, S.

    2003-01-01

    Inflammatory bowel disease presents in various forms. Its increasing incidence indicates that modern lifestyle triggers disease in genetically susceptible individuals. We present a model for inflammatory bowel disease pathophysiology and review the new biological therapies available. These

  4. Advancing Functional Metagenomics using Synthetic Biology from Soil to Sequence

    DEFF Research Database (Denmark)

    van der Helm, Eric

    as ‘functional metagenomics’, the DNA of these bacteria can be recovered from the environment and used by host-bacteria which can be grown in a lab. This allows us to make use of the capabilities of the billions of bacteria that a represent in the environment without actually growing them but by making use......-viral molecules by making use of DNA from microorganisms found in soil. In this thesis I describe the application of the relatively new nanopore sequencing technology to read the DNA, which was obtained using theprevious mentioned methods. Our deFUME webserver makes it easier for researchers to investigate...

  5. Functional and social limitations after facial palsy: expanded and independent validation of the Italian version of the facial disability index.

    Science.gov (United States)

    Pavese, Chiara; Cecini, Miriam; Camerino, Nora; De Silvestri, Annalisa; Tinelli, Carmine; Bejor, Maurizio; Dalla Toffola, Elena

    2014-09-01

    The Facial Disability Index (FDI) is widely used for self-assessment of functional impairment and quality of life in patients with facial palsy. The study aim was to complete the validation of the FDI by generating an Italian version (IT-FDI) and evaluating its clinimetric properties. This was a longitudinal, observational measurement study. The questionnaire was translated, cross-culturally adapted, and administered to 100 consecutive participants (outpatients) with facial palsy. The clinical severity of facial palsy, impairments in physical and social function, and quality of life were evaluated with the Sunnybrook Facial Grading System, IT-FDI, and 12-Item Short-Form Health Survey. The IT-FDI showed excellent test-retest reliability for every item and for total scores (intraclass correlation coefficients of .93 and .84 for physical function subscale and social/well-being function subscale, respectively). The IT-FDI confirmed the high internal consistency of the original version, with theta coefficients of .82 for the physical function subscale and .78 for the social/well-being function subscale. The physical function subscale correlated with the Sunnybrook Facial Grading System composite score (r=.44), and the social/well-being function subscale correlated with the 12-Item Short-Form Health Survey mental component (r=.55). The IT-FDI confirmed the good responsiveness of the original version, as expressed by effect size, standardized response mean, and responsiveness ratio of, respectively, 1, 1.03, and 1.21 for the physical function subscale and 0.75, 0.83, and 1.15 for the social/well-being function subscale. Responsiveness was evaluated with a limited number of participants. The results demonstrated the test-retest reliability for all items of the FDI and confirmed its internal consistency, construct validity, and responsiveness with an independent and larger clinical subset. This study completes the validation of the FDI and provides the first validated

  6. [Adipogenic function and other biologic effects of insulin].

    Science.gov (United States)

    Pankov, Y A

    2016-01-01

    Studies on experimental animals with knockout of the insulin receptor gene Insr (in the whole body or in certain tissues) and/or related genes encoding proteins involved in realization of insulin signal transduction in target cells, have made an important contribution to the elucidation of insulin regulation of metabolism, particularly fat metabolism. Since the whole insulin secreted by b-cells, together with the products of gastrointestinal tract digestion of proteins, fats, and carbohydrates reach the liver, the latter is the first organ on which this hormone acts. The liver employs released amino acids for synthesis of proteins, including apoproteins for various lipoproteins. Glucose is used for synthesis of glycogen, fatty acids, and triglycerides, which enter all the organs in very low density lipoproteins (VLDL). The LIRKO mice with knockout of the Insr gene in the liver demonstrated inhibition of synthesis of macromolecular compounds from amino acids, glucose, and fatty acids. Low molecular weight substances demonstrated increased entry to circulation, and together with other disorders induced hyperglycemia. In LIRKO mice blood glucose levels and glucose tolerance demonstrated time-dependent normalization and at later stages the increase in glucose levels was replaced by hypoglycemia. These changes can be well explained if we take into consideration that one of the main functions of insulin consists in stimulation of energy accumulation by means of activation of triglyceride deposition in adipose tissue. FIRKO mice with selective knockout of adipose tissue Insr were characterized by decreased uptake of glucose in adipocytes, and its transformation into lipids. However, the level of body fat in animals remained normal, possibly due to preserved insulin receptor in the liver and insulin-induced activation of triglyceride production which maintained normal levels of body fat stores, the effective functioning of adipose tissue and secretion of leptin by

  7. The biology and function of exosomes in cancer

    Science.gov (United States)

    Kalluri, Raghu

    2016-01-01

    Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40–150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathways in cells they fuse or interact with. Exosomes are detected in the tumor microenvironment, and emerging evidence suggests that they play a role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes can be used as liquid biopsies and noninvasive biomarkers for early detection, diagnosis, and treatment of cancer patients. PMID:27035812

  8. Development of biological functional material and product from Nelumbo nucifera

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Il Yun; Park, Yong Dae; Jin, Chang Hyun; Choi, Dae Seong

    2008-01-15

    The solvent extracts of Nelumbo nucifera G. were investigated for the activities of antioxidant, whitening, anti-wrinkle and antimicrobial effects to apply as a functional ingredient for cosmetic products. The electron donating ability of irradiated NN-L extract was above 85% at the concentration of 50ppm. The superoxide dismutase(SOD)-like activity of irradiated NN-L extract was about 76% at 1,000ppm concentration. The xanthine oxidase inhibitory effect of irradiated NN-L extract was about 15% at 1,000ppm. The tyrosinase inhibitory effect of irradiated NN-L extract was about 18% at 1,000ppm. Anti-wrinkle effect, the elastase inhibition activity of irradiated NN-L extract was about 45% at 1,000ppm concentration. All these findings suggested that Nelumbo nucifera G. has a great potential as a cosmeceutical ingredient.

  9. Biological function of activation-induced cytidine deaminase (AID

    Directory of Open Access Journals (Sweden)

    Ritu Kumar

    2014-10-01

    Full Text Available Activation-induced Cytidine Deaminase (AID is an essential regulator of B cell diversification, but its full range of action has until recently been an enigma. Based on homology, it was originally proposed to be an RNA-editing enzyme, but so far, no RNA substrates are known. Rather, it functions by deaminating cytidine, and in this manner, coupled with base-excision repair or mismatch repair machinery, it is a natural mutator. This allows it to play a central role in adaptive immunity, whereby it initiates the processes of class switch recombination and somatic hypermutation to help generate a diverse and high-affinity repertoire of immunoglobulin isotypes. More recently, it has been appreciated that methylated cytidine, already known as a key epigenetic mark on DNA controlling gene expression, can also be a target for AID modification. Coupled with repair machinery, this can facilitate the active removal of methylated DNA. This activity can impact the process of cellular reprogramming, including transition of a somatic cell to pluripotency, which requires major reshuffling of epigenetic memory. Thus, seemingly disparate roles for AID in controlling immune diversity and epigenetic memory have a common mechanistic basis. However, the very activity that is so useful for B cell diversity and cellular reprogramming is dangerous for the integrity of the genome. Thus, AID expression and activity is tightly regulated, and deregulation is associated with diseases including cancer. Here, we review the range of AID functions with a focus on its mechanisms of action and regulation. Major questions remain to be answered concerning how and when AID is targeted to specific loci and how this impacts development and disease.

  10. Biological Functions of the Secretome of Neisseria meningitidis.

    Science.gov (United States)

    Tommassen, Jan; Arenas, Jesús

    2017-01-01

    Neisseria meningitidis is a Gram-negative bacterial pathogen that normally resides as a commensal in the human nasopharynx but occasionally causes disease with high mortality and morbidity. To interact with its environment, it transports many proteins across the outer membrane to the bacterial cell surface and into the extracellular medium for which it deploys the common and well-characterized autotransporter, two-partner and type I secretion mechanisms, as well as a recently discovered pathway for the surface exposure of lipoproteins. The surface-exposed and secreted proteins serve roles in host-pathogen interactions, including adhesion to host cells and extracellular matrix proteins, evasion of nutritional immunity imposed by iron-binding proteins of the host, prevention of complement activation, neutralization of antimicrobial peptides, degradation of immunoglobulins, and permeabilization of epithelial layers. Furthermore, they have roles in interbacterial interactions, including the formation and dispersal of biofilms and the suppression of the growth of bacteria competing for the same niche. Here, we will review the protein secretion systems of N. meningitidis and focus on the functions of the secreted proteins.

  11. Nuclear speckles: molecular organization, biological function and role in disease.

    Science.gov (United States)

    Galganski, Lukasz; Urbanek, Martyna O; Krzyzosiak, Wlodzimierz J

    2017-10-13

    The nucleoplasm is not homogenous; it consists of many types of nuclear bodies, also known as nuclear domains or nuclear subcompartments. These self-organizing structures gather machinery involved in various nuclear activities. Nuclear speckles (NSs) or splicing speckles, also called interchromatin granule clusters, were discovered as sites for splicing factor storage and modification. Further studies on transcription and mRNA maturation and export revealed a more general role for splicing speckles in RNA metabolism. Here, we discuss the functional implications of the localization of numerous proteins crucial for epigenetic regulation, chromatin organization, DNA repair and RNA modification to nuclear speckles. We highlight recent advances suggesting that NSs facilitate integrated regulation of gene expression. In addition, we consider the influence of abundant regulatory and signaling proteins, i.e. protein kinases and proteins involved in protein ubiquitination, phosphoinositide signaling and nucleoskeletal organization, on pre-mRNA synthesis and maturation. While many of these regulatory proteins act within NSs, direct evidence for mRNA metabolism events occurring in NSs is still lacking. NSs contribute to numerous human diseases, including cancers and viral infections. In addition, recent data have demonstrated close relationships between these structures and the development of neurological disorders. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Production and biological function of volatile esters in Saccharomyces cerevisiae.

    Science.gov (United States)

    Saerens, Sofie M G; Delvaux, Freddy R; Verstrepen, Kevin J; Thevelein, Johan M

    2010-03-01

    The need to understand and control ester synthesis is driven by the fact that esters play a key role in the sensorial quality of fermented alcoholic beverages like beer, wine and sake. As esters are synthesized in yeast via several complex metabolic pathways, there is a need to gain a clear understanding of ester metabolism and its regulation. The individual genes involved, their functions and regulatory mechanisms have to be identified. In alcoholic beverages, there are two important groups of esters: the acetate esters and the medium-chain fatty acid (MCFA) ethyl esters. For acetate ester synthesis, the genes involved have already been cloned and characterized. Also the biochemical pathways and the regulation of acetate ester synthesis are well defined. With respect to the molecular basis of MCFA ethyl ester synthesis, however, significant progress has only recently been made. Next to the characterization of the biochemical pathways and regulation of ester synthesis, a new and more important question arises: what is the advantage for yeast to produce these esters? Several hypotheses have been proposed in the past, but none was satisfactorily. This paper reviews the current hypotheses of ester synthesis in yeast in relation to the complex regulation of the alcohol acetyl transferases and the different factors that allow ester formation to be controlled during fermentation.

  13. Biological Functions of the Secretome of Neisseria meningitidis

    Directory of Open Access Journals (Sweden)

    Jan Tommassen

    2017-06-01

    Full Text Available Neisseria meningitidis is a Gram-negative bacterial pathogen that normally resides as a commensal in the human nasopharynx but occasionally causes disease with high mortality and morbidity. To interact with its environment, it transports many proteins across the outer membrane to the bacterial cell surface and into the extracellular medium for which it deploys the common and well-characterized autotransporter, two-partner and type I secretion mechanisms, as well as a recently discovered pathway for the surface exposure of lipoproteins. The surface-exposed and secreted proteins serve roles in host-pathogen interactions, including adhesion to host cells and extracellular matrix proteins, evasion of nutritional immunity imposed by iron-binding proteins of the host, prevention of complement activation, neutralization of antimicrobial peptides, degradation of immunoglobulins, and permeabilization of epithelial layers. Furthermore, they have roles in interbacterial interactions, including the formation and dispersal of biofilms and the suppression of the growth of bacteria competing for the same niche. Here, we will review the protein secretion systems of N. meningitidis and focus on the functions of the secreted proteins.

  14. Towards understanding the biological function of hopanoids (Invited)

    Science.gov (United States)

    Doughty, D. M.; Hunter, R.; Summons, R. E.; Newman, D. K.

    2010-12-01

    Rhodopseudomonas palustris TIE-1 expresses bacterial hopanoid lipids that are structurally similar and evolutionarily related to eukaryotic sterols. The genome of R. palustris TIE-1 contains two copies of the hpnN gene (hpnN1 and hpnN2) that are orthologs of genes encoding eukaryotic sterol and lipid transporters. Hopanoid localization to the outer membrane was found to be dependent upon hpnN1. Since the cell cycle of R. palustris TIE-1 is obligately bimodal with each cell division resulting in the generation of one mother and one swarmer cell, evidence was obtained that hopanoids where specifically localized to the outer membrane of mother cells. The sequestration of hopanoids to the mother cells was also disrupted by the deletion of the hpnN1 gene. Mutants lacking the hopanoid transporters were able to grow normally at 30 °C but showed decreased growth at 38 °C. The hopanoid transporter mutant formed cellular filaments when grown at elevated temperature. Because sedimentary steranes and hopanes comprise some of the earliest evidence for the emergence of distinct bacteria and eukaryotic phyla, a better appreciation of the function of hopanoids will improve our ability to interpret the evolution of life on Earth.

  15. Functionalized diamond nanopowder for phosphopeptides enrichment from complex biological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, Dilshad [Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800 (Pakistan); Najam-ul-Haq, Muhammad, E-mail: najamulhaq@bzu.edu.pk [Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800 (Pakistan); Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innrain 80-82, A-6020 Innsbruck (Austria); Jabeen, Fahmida; Ashiq, Muhammad N.; Athar, Muhammad [Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800 (Pakistan); Rainer, Matthias; Huck, Christian W.; Bonn, Guenther K. [Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innrain 80-82, A-6020 Innsbruck (Austria)

    2013-05-02

    Graphical abstract: -- Highlights: •Derivatization of diamond nanopowder as IMAC and RP. •Characterization with SEM, EDX and FT-IR. •Phosphopeptide enrichment from standard as well as real samples. •Desalting and human serum profiling with reproducible results. •MALDI-MS analysis with database identification. -- Abstract: Diamond is known for its high affinity and biocompatibility towards biomolecules and is used exclusively in separation sciences and life science research. In present study, diamond nanopowder is derivatized as Immobilized Metal Ion Affinity Chromatographic (IMAC) material for the phosphopeptides enrichment and as Reversed Phase (C-18) media for the desalting of complex mixtures and human serum profiling through MALDI-TOF-MS. Functionalized diamond nanopowder is characterized by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy. Diamond-IMAC is applied to the standard protein (β-casein), spiked human serum, egg yolk and non-fat milk for the phosphopeptides enrichment. Results show the selectivity of synthesized IMAC-diamond immobilized with Fe{sup 3+} and La{sup 3+} ions. To comprehend the elaborated use, diamond-IMAC is also applied to the serum samples from gall bladder carcinoma for the potential biomarkers. Database search is carried out by the Mascot program ( (www.matrixscience.com)) for the assignment of phosphorylation sites. Diamond nanopowder is thus a separation media with multifunctional use and can be applied to cancer protein profiling for the diagnosis and biomarker identification.

  16. The reflection of life functional entailment and imminence in relational biology

    CERN Document Server

    Louie, A H

    2013-01-01

    A. H. Louie’s The Reflection of Life: Functional Entailment and Imminence in Relational Biology is a continuation of the exploratory journey in relational biology which began with his 2009 monograph More Than Life Itself: A Synthetic Continuation in Relational Biology. The theme of his first book was ‘What is life?’; the theme of this sequel is “How do two life forms interact?” Biology is a subject concerned with organization of relations. Relational biology is the approach that advocates ‘function dictates structure”, rather than ‘structure implies function’. It is mathematics decoded into biological realizations. The book demonstrates some of the powers of the approach of relational biology, and illustrates how pertinent problems in biology can be better addressed this way. In the first volume the theory was developed by using partially ordered sets, lattices, simulations, models, Aristotle’s four causes, graphs, categories, simple and complex systems, anticipatory systems, and metabolis...

  17. Expanding the Repertoire of Carbapenem-Hydrolyzing Metallo-ß-Lactamases by Functional Metagenomic Analysis of Soil Microbiota

    Science.gov (United States)

    Gudeta, Dereje D.; Bortolaia, Valeria; Pollini, Simona; Docquier, Jean-Denis; Rossolini, Gian M.; Amos, Gregory C. A.; Wellington, Elizabeth M. H.; Guardabassi, Luca

    2016-01-01

    Carbapenemases are bacterial enzymes that hydrolyze carbapenems, a group of last-resort β-lactam antibiotics used for treatment of severe bacterial infections. They belong to three β-lactamase classes based amino acid sequence (A, B, and D). The aim of this study was to elucidate occurrence, diversity and functionality of carbapenemase-encoding genes in soil microbiota by functional metagenomics. Ten plasmid libraries were generated by cloning metagenomic DNA from agricultural (n = 6) and grassland (n = 4) soil into Escherichia coli. The libraries were cultured on amoxicillin-containing agar and up to 100 colonies per library were screened for carbapenemase production by CarbaNP test. Presumptive carbapenemases were characterized with regard to DNA sequence, minimum inhibitory concentration (MIC) of β-lactams, and imipenem hydrolysis. Nine distinct class B carbapenemases, also known as metallo-beta-lactamases (MBLs), were identified in six soil samples, including two subclass B1 (GRD23-1 and SPN79-1) and seven subclass B3 (CRD3-1, PEDO-1, GRD33-1, ESP-2, ALG6-1, ALG11-1, and DHT2-1). Except PEDO-1 and ESP-2, these enzymes were distantly related to any previously described MBLs (33 to 59% identity). RAIphy analysis indicated that six enzymes (CRD3-1, GRD23-1, DHT2-1, SPN79-1, ALG6-1, and ALG11-1) originated from Proteobacteria, two (PEDO-1 and ESP-2) from Bacteroidetes and one (GRD33-1) from Gemmatimonadetes. All MBLs detected in soil microbiota were functional when expressed in E. coli, resulting in detectable imipenem-hydrolyzing activity and significantly increased MICs of clinically relevant ß-lactams. Interestingly, the MBLs yielded by functional metagenomics generally differed from those detected in the same soil samples by antibiotic selective culture, showing that the two approaches targeted different subpopulations in soil microbiota. PMID:28082950

  18. Expanding the Repertoire of Carbapenem-Hydrolyzing Metallo-ß-Lactamases by Functional Metagenomic Analysis of Soil Microbiota.

    Science.gov (United States)

    Gudeta, Dereje D; Bortolaia, Valeria; Pollini, Simona; Docquier, Jean-Denis; Rossolini, Gian M; Amos, Gregory C A; Wellington, Elizabeth M H; Guardabassi, Luca

    2016-01-01

    Carbapenemases are bacterial enzymes that hydrolyze carbapenems, a group of last-resort β-lactam antibiotics used for treatment of severe bacterial infections. They belong to three β-lactamase classes based amino acid sequence (A, B, and D). The aim of this study was to elucidate occurrence, diversity and functionality of carbapenemase-encoding genes in soil microbiota by functional metagenomics. Ten plasmid libraries were generated by cloning metagenomic DNA from agricultural (n = 6) and grassland (n = 4) soil into Escherichia coli. The libraries were cultured on amoxicillin-containing agar and up to 100 colonies per library were screened for carbapenemase production by CarbaNP test. Presumptive carbapenemases were characterized with regard to DNA sequence, minimum inhibitory concentration (MIC) of β-lactams, and imipenem hydrolysis. Nine distinct class B carbapenemases, also known as metallo-beta-lactamases (MBLs), were identified in six soil samples, including two subclass B1 (GRD23-1 and SPN79-1) and seven subclass B3 (CRD3-1, PEDO-1, GRD33-1, ESP-2, ALG6-1, ALG11-1, and DHT2-1). Except PEDO-1 and ESP-2, these enzymes were distantly related to any previously described MBLs (33 to 59% identity). RAIphy analysis indicated that six enzymes (CRD3-1, GRD23-1, DHT2-1, SPN79-1, ALG6-1, and ALG11-1) originated from Proteobacteria, two (PEDO-1 and ESP-2) from Bacteroidetes and one (GRD33-1) from Gemmatimonadetes. All MBLs detected in soil microbiota were functional when expressed in E. coli, resulting in detectable imipenem-hydrolyzing activity and significantly increased MICs of clinically relevant ß-lactams. Interestingly, the MBLs yielded by functional metagenomics generally differed from those detected in the same soil samples by antibiotic selective culture, showing that the two approaches targeted different subpopulations in soil microbiota.

  19. Improving Care Transitions Management: Examining the Role of Accountable Care Organization Participation and Expanded Electronic Health Record Functionality.

    Science.gov (United States)

    Huber, Thomas P; Shortell, Stephen M; Rodriguez, Hector P

    2017-08-01

    Examine the extent to which physician organization participation in an accountable care organization (ACO) and electronic health record (EHR) functionality are associated with greater adoption of care transition management (CTM) processes. A total of 1,398 physician organizations from the third National Study of Physician Organization survey (NSPO3), a nationally representative sample of medical practices in the United States (January 2012-May 2013). We used data from the third National Study of Physician Organization survey (NSPO3) to assess medical practice characteristics, including CTM processes, ACO participation, EHR functionality, practice type, organization size, ownership, public reporting, and pay-for-performance participation. Multivariate linear regression models estimated the extent to which ACO participation and EHR functionality were associated with greater CTM capabilities, controlling for practice size, ownership, public reporting, and pay-for-performance participation. Approximately half (52.4 percent) of medical practices had a formal program for managing care transitions in place. In adjusted analyses, ACO participation (p management of care transitions by physician organizations. © Health Research and Educational Trust.

  20. Ex-vivo clonally expanded B lymphocytes infiltrating colorectal carcinoma are of mature immunophenotype and produce functional IgG.

    Science.gov (United States)

    Maletzki, Claudia; Jahnke, Annika; Ostwald, Christiane; Klar, Ernst; Prall, Friedrich; Linnebacher, Michael

    2012-01-01

    Tumor infiltrating B cells (TiBc) have not yet been investigated in detail. This may at least in part be due to technical difficulties. Here we describe a straightforward and reproducible method to isolate and culture TiBc from primary colorectal carcinomas (CRC). TiBc cultures were generated by Epstein-Barr virus (EBV) immortalization. With this method, monoclonal TiBc cultures were obtained for 14/19 CRCs. As assessed by flow cytometry and ELISA, TiBc showed an activated immunophenotype (CD23(+), CD80(+)) and produced immunoglobulin (Ig; IgG secretion in 55% of the cultures). In functional in vitro analysis, most of the IgGs specifically bound to allogeneic CRC target cells. These data suggest that TiBc are antigen-experienced and thus may exhibit functionality in situ. Additionally, mini-cultures generated from 12 further CRCs revealed TiBc outgrowth exclusively in the presence of EBV. In summary, this simple method provides a cellular tool and our data set the stage for analysing the bivalent role of TiBc; being antigen-presenting cells on the one hand and tumor-specific antibody producers on the other. Additionally, the generation of long-term TiBc cultures and their monoclonal Ig may serve to identify novel tumor-specific antigens.

  1. Expanding the Repertoire of Carbapenem-Hydrolyzing Metallo-ß-Lactamases by Functional Metagenomic Analysis of Soil Microbiota

    DEFF Research Database (Denmark)

    Gudeta, Dereje D.; Bortolaia, Valeria; Pollini, Simona

    2016-01-01

    as metallo-beta-lactamases (MBLs), were identified in six soil samples, including two subclass B1 (GRD23-1 and SPN79-1) and seven subclass B3 (CRD3-1, PEDO-1, GRD33-1, ESP-2, ALG6-1, ALG11-1, and DHT2-1). Except PEDO-1 and ESP-2, these enzymes were distantly related to any previously described MBLs (33 to 59......% identity). RAIphy analysis indicated that six enzymes (CRD3-1, GRD23-1, DHT2-1, SPN79-1, ALG6-1, and ALG11-1) originated from Proteobacteria, two (PEDO-1 and ESP-2) from Bacteroidetes and one (GRD33-1) from Gemmatimonadetes. All MBLs detected in soil microbiota were functional when expressed in E. coli......, resulting in detectable imipenem-hydrolyzing activity and significantly increased MICs of clinically relevant ss-lactams. Interestingly, the MBLs yielded by functional metagenomics generally differed from those detected in the same soil samples by antibiotic selective culture, showing that the two...

  2. Ex-vivo clonally expanded B lymphocytes infiltrating colorectal carcinoma are of mature immunophenotype and produce functional IgG.

    Directory of Open Access Journals (Sweden)

    Claudia Maletzki

    Full Text Available BACKGROUND: Tumor infiltrating B cells (TiBc have not yet been investigated in detail. This may at least in part be due to technical difficulties. Here we describe a straightforward and reproducible method to isolate and culture TiBc from primary colorectal carcinomas (CRC. METHODS/RESULTS: TiBc cultures were generated by Epstein-Barr virus (EBV immortalization. With this method, monoclonal TiBc cultures were obtained for 14/19 CRCs. As assessed by flow cytometry and ELISA, TiBc showed an activated immunophenotype (CD23(+, CD80(+ and produced immunoglobulin (Ig; IgG secretion in 55% of the cultures. In functional in vitro analysis, most of the IgGs specifically bound to allogeneic CRC target cells. These data suggest that TiBc are antigen-experienced and thus may exhibit functionality in situ. Additionally, mini-cultures generated from 12 further CRCs revealed TiBc outgrowth exclusively in the presence of EBV. CONCLUSION: In summary, this simple method provides a cellular tool and our data set the stage for analysing the bivalent role of TiBc; being antigen-presenting cells on the one hand and tumor-specific antibody producers on the other. Additionally, the generation of long-term TiBc cultures and their monoclonal Ig may serve to identify novel tumor-specific antigens.

  3. Schematic and realistic biological motion identification in children with high-functioning autism spectrum disorder.

    Science.gov (United States)

    Wright, Kristyn; Kelley, Elizabeth; Poulin-Dubois, Diane

    2014-10-01

    Research investigating biological motion perception in children with ASD has revealed conflicting findings concerning whether impairments in biological motion perception exist. The current study investigated how children with high-functioning ASD (HF-ASD) performed on two tasks of biological motion identification: a novel schematic motion identification task and a point-light biological motion identification task. Twenty-two HFASD children were matched with 21 TD children on gender, non-verbal mental, and chronological, age (M years = 6.72). On both tasks, HF-ASD children performed with similar accuracy as TD children. Across groups, children performed better on animate than on inanimate trials of both tasks. These findings suggest that HF-ASD children's identification of both realistic and schematic biological motion identification is unimpaired.

  4. Evolutionary cell biology: functional insight from “endless forms most beautiful”

    Science.gov (United States)

    Richardson, Elisabeth; Zerr, Kelly; Tsaousis, Anastasios; Dorrell, Richard G.; Dacks, Joel B.

    2015-01-01

    In animal and fungal model organisms, the complexities of cell biology have been analyzed in exquisite detail and much is known about how these organisms function at the cellular level. However, the model organisms cell biologists generally use include only a tiny fraction of the true diversity of eukaryotic cellular forms. The divergent cellular processes observed in these more distant lineages are still largely unknown in the general scientific community. Despite the relative obscurity of these organisms, comparative studies of them across eukaryotic diversity have had profound implications for our understanding of fundamental cell biology in all species and have revealed the evolution and origins of previously observed cellular processes. In this Perspective, we will discuss the complexity of cell biology found across the eukaryotic tree, and three specific examples of where studies of divergent cell biology have altered our understanding of key functional aspects of mitochondria, plastids, and membrane trafficking. PMID:26668171

  5. Diurnal rhythmicity in biological processes involved in bioavailability of functional food factors.

    Science.gov (United States)

    Tsurusaki, Takashi; Sakakibara, Hiroyuki; Aoshima, Yoshiki; Yamazaki, Shunsuke; Sakono, Masanobu; Shimoi, Kayoko

    2013-05-01

    In the past few decades, many types of functional factors have been identified in dietary foods; for example, flavonoids are major groups widely distributed in the plant kingdom. However, the absorption rates of the functional food factors are usually low, and many of these are difficult to be absorbed in the intact forms because of metabolization by biological processes during absorption. To gain adequate beneficial effects, it is therefore mandatory to know whether functional food factors are absorbed in sufficient quantity, and then reach target organs while maintaining beneficial effects. These are the reasons why the bioavailability of functional food factors has been well investigated using rodent models. Recently, many of the biological processes have been reported to follow diurnal rhythms recurring every 24 h. Therefore, absorption and metabolism of functional food factors influenced by the biological processes may vary with time of day. Consequently, the evaluation of the bioavailability of functional food factors using rodent models should take into consideration the timing of consumption. In this review, we provide a perspective overview of the diurnal rhythm of biological processes involved in the bioavailability of functional food factors, particularly flavonoids.

  6. Increased Use of Care Management Processes and Expanded Health Information Technology Functions by Practice Ownership and Medicaid Revenue.

    Science.gov (United States)

    Rodriguez, Hector P; McClellan, Sean R; Bibi, Salma; Casalino, Lawrence P; Ramsay, Patricia P; Shortell, Stephen M

    2016-06-01

    Practice ownership and Medicaid revenue may affect the use of care management processes (CMPs) for chronic conditions and expansion of health information technology (HIT). Using a national cohort of medical practices, we compared the use of CMPs and HIT from 2006/2008 to 2013 by practice ownership and level of Medicaid revenue. Poisson regression models estimated changes in CMP use, and linear regression estimated changes in HIT, by practice ownership and Medicaid patient revenue, controlling for other practice characteristics. Compared with physician-owned practices, system-owned practices adopted a greater number of CMPs and HIT functions over time (p revenue (≥30.0%) was associated with less adoption of CMPs (p revenue were more likely than physician-owned practices with high Medicaid revenue to adopt CMPs over time. System and community health center ownership appear to help high Medicaid practices overcome CMP adoption constraints. © The Author(s) 2015.

  7. Expanding the Repertoire of Carbapenem-Hydrolyzing Metallo-ß-Lactamases by Functional Metagenomic Analysis of Soil Microbiota

    DEFF Research Database (Denmark)

    Gudeta, Dereje D.; Bortolaia, Valeria; Pollini, Simona

    2016-01-01

    as metallo-beta-lactamases (MBLs), were identified in six soil samples, including two subclass B1 (GRD23-1 and SPN79-1) and seven subclass B3 (CRD3-1, PEDO-1, GRD33-1, ESP-2, ALG6-1, ALG11-1, and DHT2-1). Except PEDO-1 and ESP-2, these enzymes were distantly related to any previously described MBLs (33 to 59......% identity). RAIphy analysis indicated that six enzymes (CRD3-1, GRD23-1, DHT2-1, SPN79-1, ALG6-1, and ALG11-1) originated from Proteobacteria, two (PEDO-1 and ESP-2) from Bacteroidetes and one (GRD33-1) from Gemmatimonadetes. All MBLs detected in soil microbiota were functional when expressed in E. coli...

  8. Application of femtosecond-pulsed lasers for direct optical manipulation of biological functions

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Jonghee; Park, Junseong; Jong Choi, Won [Department of Bio and Brain Engineering, KAIST, Daejeon (Korea, Republic of); Choi, Myunghwan [Graduate School of Nanoscience and Technology, KAIST, Daejeon (Korea, Republic of); Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA (United States); Choi, Chulhee [Department of Bio and Brain Engineering, KAIST, Daejeon (Korea, Republic of); KAIST Institute for the BioCentury, KAIST, Daejeon (Korea, Republic of)

    2013-03-15

    Absorption of photon energy by cells or tissue can evoke photothermal, photomechanical, and photochemical effects, depending on the density of the deposited energy. Photochemical effects require a low energy density and can be used for reversible modulation of biological functions. Ultrashort-pulsed lasers have a high intensity due to the short pulse duration, despite its low average energy. Through nonlinear absorption, these lasers can deliver very high peak energy into the submicrometer focus area without causing collateral damage. Absorbed energy delivered by ultrashort-pulsed laser irradiation induces free electrons, which can be readily converted to reactive oxygen species (ROS) and related free radicals in the localized region. Free radicals are best known to induce irreversible biological effects via oxidative modification; however, they have also been proposed to modulate biological functions by releasing calcium ions from intracellular organelles. Calcium can evoke variable biological effects in both excitable and nonexcitable cell types. Controlled stimulation by ultrashort laser pulses generate intracellular calcium waves that can modulate many biological functions, such as cardiomyocyte beat rate, muscle contractility, and blood-brain barrier (BBB) permeability. This article presents optical methods that are useful therapeutic and research tools in the biomedical field and discuss the possible mechanisms responsible for biological modulation by ultrashort-pulsed lasers, especially femtosecond-pulsed lasers. (copyright 2012 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  9. An overview of the applicability of functional diversity in Biological Conservation.

    Science.gov (United States)

    Freitas, J R; Mantovani, W

    2017-10-23

    Functional diversity is increasingly pointed as a useful approach to reach Biological Conservation goals. Here, we provide an overview of the functional diversity approach status in the Biological Conservation field. We sought for peer-reviewed papers published over a period of twenty years (from 1994 to 2014). First we used the general topic "functional diversity" and then refined our search using the key-word "conservation". We have identified the conservation strategies addressed, the organism studied, and the continent of study site in each paper. Thirteen classes of conservation strategies were identified. Plants were the most commonly studied organism group and most study-sites were located in Europe. The functional diversity approach was introduced in the Biological Conservation field in the early 2000's and its inclusion in conservation strategies is broadly advised. However, the number of papers that operationalise such inclusion by developing models and systems is still low. Functional diversity responds differently and eventually better than other measures to changes in land use and management, which suggests that this approach can potentially better predict the impacts. More studies are needed to corroborate this hypothesis. We pointed out knowledge gaps regarding identification of the responses for functional diversity about urban impacts and in research on the level of management intensity of land needed to maintain functional diversity. We recommend the use of functional diversity measures to find ecological indicators. Future studies should focus on the development of functional diversity measures of other taxa beyond plants as well as test hypothesis in tropical ecosystems.

  10. Biology

    Indian Academy of Sciences (India)

    I am particularly happy that the Academy is bringing out this document by Professor M S. Valiathan on Ayurvedic Biology. It is an effort to place before the scientific community, especially that of India, the unique scientific opportunities that arise out of viewing Ayurveda from the perspective of contemporary science, its tools ...

  11. Expandable LED array interconnect

    Science.gov (United States)

    Yuan, Thomas Cheng-Hsin; Keller, Bernd

    2011-03-01

    A light emitting device that can function as an array element in an expandable array of such devices. The light emitting device comprises a substrate that has a top surface and a plurality of edges. Input and output terminals are mounted to the top surface of the substrate. Both terminals comprise a plurality of contact pads disposed proximate to the edges of the substrate, allowing for easy access to both terminals from multiple edges of the substrate. A lighting element is mounted to the top surface of the substrate. The lighting element is connected between the input and output terminals. The contact pads provide multiple access points to the terminals which allow for greater flexibility in design when the devices are used as array elements in an expandable array.

  12. Composite Structural Motifs of Binding Sites for Delineating Biological Functions of Proteins

    Science.gov (United States)

    Kinjo, Akira R.; Nakamura, Haruki

    2012-01-01

    Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs that represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures. PMID:22347478

  13. Revised computational metagenomic processing uncovers hidden and biologically meaningful functional variation in the human microbiome.

    Science.gov (United States)

    Manor, Ohad; Borenstein, Elhanan

    2017-02-08

    Recent metagenomic analyses of the human gut microbiome identified striking variability in its taxonomic composition across individuals. Notably, however, these studies often reported marked functional uniformity, with relatively little variation in the microbiome's gene composition or in its overall metabolic capacity. Here, we address this surprising discrepancy between taxonomic and functional variations and set out to track its origins. Specifically, we demonstrate that the functional uniformity observed in microbiome studies can be attributed, at least partly, to common computational metagenomic processing procedures that mask true functional variation across microbiome samples. We identify several such procedures, including commonly used practices for gene abundance normalization, mapping of gene families to functional pathways, and gene family aggregation. We show that accounting for these factors and using revised metagenomic processing procedures uncovers such hidden functional variation, significantly increasing observed variation in the abundance of functional elements across samples. Importantly, we find that this uncovered variation is biologically meaningful and that it is associated with both host identity and health. Accurate characterization of functional variation in the microbiome is essential for comparative metagenomic analyses in health and disease. Our finding that metagenomic processing procedures mask underlying and biologically meaningful functional variation therefore highlights an important challenge such studies may face. Alternative schemes for metagenomic processing that uncover this hidden functional variation can facilitate improved metagenomic analysis and help pinpoint disease- and host-associated shifts in the microbiome's functional capacity.

  14. BeeSpace Navigator: exploratory analysis of gene function using semantic indexing of biological literature.

    Science.gov (United States)

    Sen Sarma, Moushumi; Arcoleo, David; Khetani, Radhika S; Chee, Brant; Ling, Xu; He, Xin; Jiang, Jing; Mei, Qiaozhu; Zhai, ChengXiang; Schatz, Bruce

    2011-07-01

    With the rapid decrease in cost of genome sequencing, the classification of gene function is becoming a primary problem. Such classification has been performed by human curators who read biological literature to extract evidence. BeeSpace Navigator is a prototype software for exploratory analysis of gene function using biological literature. The software supports an automatic analogue of the curator process to extract functions, with a simple interface intended for all biologists. Since extraction is done on selected collections that are semantically indexed into conceptual spaces, the curation can be task specific. Biological literature containing references to gene lists from expression experiments can be analyzed to extract concepts that are computational equivalents of a classification such as Gene Ontology, yielding discriminating concepts that differentiate gene mentions from other mentions. The functions of individual genes can be summarized from sentences in biological literature, to produce results resembling a model organism database entry that is automatically computed. Statistical frequency analysis based on literature phrase extraction generates offline semantic indexes to support these gene function services. The website with BeeSpace Navigator is free and open to all; there is no login requirement at www.beespace.illinois.edu for version 4. Materials from the 2010 BeeSpace Software Training Workshop are available at www.beespace.illinois.edu/bstwmaterials.php.

  15. Chemical genomics in plant biology.

    Science.gov (United States)

    Sadhukhan, Ayan; Sahoo, Lingaraj; Panda, Sanjib Kumar

    2012-06-01

    Chemical genomics is a newly emerged and rapidly progressing field in biology, where small chemical molecules bind specifically and reversibly to protein(s) to modulate their function(s), leading to the delineation and subsequent unravelling of biological processes. This approach overcomes problems like lethality and redundancy of classical genetics. Armed with the powerful techniques of combinatorial synthesis, high-throughput screening and target discovery chemical genomics expands its scope to diverse areas in biology. The well-established genetic system of Arabidopsis model allows chemical genomics to enter into the realm of plant biology exploring signaling pathways of growth regulators, endomembrane signaling cascades, plant defense mechanisms and many more events.

  16. [Recent advances of synthetic biology for production of functional ingredients in Chinese materia medica].

    Science.gov (United States)

    Su, Xin-Yao; Xue, Jian-Ping; Wang, Cai-Xia

    2016-11-01

    The functional ingredients in Chinese materia medica are the main active substance for traditional Chinese medicine and most of them are secondary metabolites derivatives. Until now,the main method to obtain those functional ingredients is through direct extraction from the Chinese materia medica. However, the income is very low because of the high extraction costs and the decreased medicinal plants. Synthetic biology technology, as a new and microbial approach, can be able to carry out large-scale production of functional ingredients and greatly ease the shortage of traditional Chinese medicine ingredients. This review mainly focused on the recent advances in synthetic biology for the functional ingredients production. Copyright© by the Chinese Pharmaceutical Association.

  17. Functional genomics bridges the gap between quantitative genetics and molecular biology

    OpenAIRE

    Lappalainen, Tuuli

    2015-01-01

    Deep characterization of molecular function of genetic variants in the human genome is becoming increasingly important for understanding genetic associations to disease and for learning to read the regulatory code of the genome. In this paper, I discuss how recent advances in both quantitative genetics and molecular biology have contributed to understanding functional effects of genetic variants, lessons learned from eQTL studies, and future challenges in this field.

  18. Functional genomics bridges the gap between quantitative genetics and molecular biology.

    Science.gov (United States)

    Lappalainen, Tuuli

    2015-10-01

    Deep characterization of molecular function of genetic variants in the human genome is becoming increasingly important for understanding genetic associations to disease and for learning to read the regulatory code of the genome. In this paper, I discuss how recent advances in both quantitative genetics and molecular biology have contributed to understanding functional effects of genetic variants, lessons learned from eQTL studies, and future challenges in this field. © 2015 Lappalainen; Published by Cold Spring Harbor Laboratory Press.

  19. Application and Optimization of Biolog EcoPlates in Functional Diversity Studies of Soil Microbial Communities

    Directory of Open Access Journals (Sweden)

    Xu Wenhuan

    2015-01-01

    Full Text Available The biological diversity contributes to many aspects of human well-being and ecosystem function, however, we have known very little about microbial diversity due to the limitations of appropriate methodology underneath it. The development of biotech have brought revolutionary progress in the study of microbial diversity in which Biolog required to pay a lot of attention due to its ability of reflecting the metabolic situation of living microbial communities and have used widely in the study of soil microbial communities. However, there are some controversies during its operation procedure and incubation process, handling large data during the analysis might have also caused trouble in the overall process. The approach based on uses of “absolute used”, “INDIRECT” function in Excel could greatly optimize the data analysis, and the increase of principle components in Principle Component Analysis (PCA were able to extract more information from original data. Besides, the method that through “Taylor” and “logic” transformation for original data before PCA analysis could achieve data analysis optimization. This paper have presented the applications and optimization of Biolog EcoPlates in studies of functional diversity of microbial communities, presented its inherent biases and prospects, provided some reference for the applications and popularization of Biolog EcoPlates for microbial study and finally, the results imply improving the knowledge of biotech in study of soil microbial functional diversity.

  20. Finite element analysis (FEA): applying an engineering method to functional morphology in anthropology and human biology.

    Science.gov (United States)

    Panagiotopoulou, O

    2009-01-01

    A fundamental research question for morphologists is how morphological variation in the skeleton relates to function. Traditional approaches have advanced our understanding of form-function relationships considerably but have limitations. Strain gauges can only record strains on a surface, and the geometry of the structure can limit where they can be bonded. Theoretical approaches, such as geometric abstractions, work well on problems with simple geometries and material properties but biological structures typically have neither of these. Finite element analysis (FEA) is a method that overcomes these problems by reducing a complex geometry into a finite number of elements with simple geometries. In addition, FEA allows strain to be modelled across the entire surface of the structure and throughout the internal structure. With advances in the processing power of computers, FEA has become more accessible and as such is becoming an increasingly popular tool to address questions about form-function relationships in development and evolution, as well as human biology generally. This paper provides an introduction to FEA including a review of the sequence of steps needed for the generation of biologically accurate finite element models that can be used for the testing of biological and functional morphology hypotheses.

  1. Fungal secretomics to probe the biological functions of lytic polysaccharide monooxygenases

    DEFF Research Database (Denmark)

    Berrin, Jean-Guy; Rosso, Marie-Noëlle; Abou Hachem, Maher

    2017-01-01

    to starch, the main carbon storage reservoir. In this review, we focus on the identification of lytic polysaccharide monooxygenases (LPMOs) and their redox partners in fungal secretomes to highlight the biological functions of these remarkable enzyme systems and we discuss future trends related to LPMO...

  2. Biological interpretation of genome-wide association studies using predicted gene functions

    NARCIS (Netherlands)

    Pers, Tune H.; Karjalainen, Juha M.; Chan, Yingleong; Westra, Harm-Jan; Wood, Andrew R.; Yang, Jian; Lui, Julian C.; Vedantam, Sailaja; Gustafsson, Stefan; Esko, Tonu; Frayling, Tim; Speliotes, Elizabeth K.; Boehnke, Michael; Raychaudhuri, Soumya; Fehrmann, Rudolf S. N.; Hirschhorn, Joel N.; Franke, Lude; Chu, Audrey Y.; Estrada, Karol; Luan, Jian'an; Kutalik, Zoltán; Amin, Najaf; Buchkovich, Martin L.; Croteau-Chonka, Damien C.; Day, Felix R.; Duan, Yanan; Fall, Tove; Fehrmann, Rudolf; Ferreira, Teresa; Jackson, Anne U.; Karjalainen, Juha; Lo, Ken Sin; Locke, Adam E.; Mägi, Reedik; Mihailov, Evelin; Porcu, Eleonora; Randall, Joshua C.; Scherag, André; Vinkhuyzen, Anna A. E.; Winkler, Thomas W.; Workalemahu, Tsegaselassie; Zhao, Jing Hua; Absher, Devin; Albrecht, Eva; Anderson, Denise; Baron, Jeffrey; Beekman, Marian; Demirkan, Ayse; Ehret, Georg B.; Feenstra, Bjarke; Feitosa, Mary F.; Fischer, Krista; Fraser, Ross M.; Goel, Anuj; Gong, Jian; Justice, E.; Kanoni, Stavroula; Kleber, Marcus E.; Kristiansson, Kati; Lim, Unhee; Lotay, Vaneet; Mangino, Massimo; Mateo Leach, Irene; Medina-Gomez, Carolina; Nalls, Michael A.; Nyholt, Dale R.; Palmer, Cameron D.; Pasko, Dorota; Pechlivanis, Sonali; Prokopenko, Inga; Ried, Janina S.; Ripke, Stephan; Shungin, Dmitry; Stancáková, Alena; Strawbridge, Rona J.; Sung, Yun Ju; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; van der Laan, Sander W.; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V.; Wang, Zhaoming; Yengo, Loïc; Zhang, Weihua; Afzal, Uzma; Ärnlöv, Johan; Arscott, Gillian M.; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J.; Berne, Christian; Blüher, Matthias; Bolton, Jennifer L.; Böttcher, Yvonne; Boyd, Heather A.; Bruinenberg, Marcel; Buckley, Brendan M.; Buyske, Steven; Caspersen, Ida H.; Chines, Peter S.; Clarke, Robert; Claudi-Boehm, Simone; Cooper, Matthew; Daw, E. Warwick; de Jong, A.; Deelen, Joris; Delgado, Graciela; Denny, Josh C.; Dhonukshe-Rutten, Rosalie; Dimitriou, Maria; Doney, Alex S. F.; Dörr, Marcus; Eklund, Niina; Eury, Elodie; Folkersen, Lasse; Garcia, Melissa E.; Geller, Frank; Giedraitis, Vilmantas; Go, Alan S.; Grallert, Harald; Grammer, Tanja B.; Gräßler, Jürgen; Grönberg, Henrik; de Groot, Lisette C. P. G. M.; Groves, Christopher J.; Haessler, Jeffrey; Haller, Toomas; Hallmans, Goran; Hannemann, Anke; Hartman, Catharina A.; Hassinen, Maija; Hayward, Caroline; Heard-Costa, Nancy L.; Helmer, Quinta; Hemani, Gibran; Henders, Anjali K.; Hillege, Hans L.; Hlatky, Mark A.; Hoffmann, Wolfgang; Hoffmann, Per; Holmen, Oddgeir; Houwing-Duistermaat, Jeanine J.; Illig, Thomas; Isaacs, Aaron; James, Alan L.; Jeff, Janina; Johansen, Berit; Johansson, Åsa; Jolley, Jennifer; Juliusdottir, Thorhildur; Junttila, Juhani; Kho, Abel N.; Kinnunen, Leena; Klopp, Norman; Kocher, Thomas; Kratzer, Wolfgang; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Lu, Yingchang; Lyssenko, Valeriya; Magnusson, Patrik K. E.; Mahajan, Anubha; Maillard, Marc; McArdle, Wendy L.; McKenzie, Colin A.; McLachlan, Stela; McLaren, Paul J.; Menni, Cristina; Merger, Sigrun; Milani, Lili; Moayyeri, Alireza; Monda, Keri L.; Morken, Mario A.; Müller, Gabriele; Müller-Nurasyid, Martina; Musk, Arthur W.; Narisu, Narisu; Nauck, Matthias; Nolte, Ilja M.; Nöthen, Markus M.; Oozageer, Laticia; Pilz, Stefan; Rayner, Nigel W.; Renstrom, Frida; Robertson, Neil R.; Rose, Lynda M.; Roussel, Ronan; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Schumacher, Fredrick R.; Schunkert, Heribert; Scott, Robert A.; Sehmi, Joban; Seufferlein, Thomas; Shi, Jianxin; Silventoinen, Karri; Smit, Johannes H.; Smith, Albert Vernon; Smolonska, Joanna; Stanton, Alice V.; Stirrups, Kathleen; Stott, David J.; Stringham, Heather M.; Sundström, Johan; Swertz, Morris A.; Syvänen, Ann-Christine; Tayo, Bamidele O.; Thorleifsson, Gudmar; Tyrer, Jonathan P.; van Dijk, Suzanne; van Schoor, Natasja M.; van der Velde, Nathalie; van Heemst, Diana; van Oort, Floor V. A.; Vermeulen, Sita H.; Verweij, Niek; Vonk, Judith M.; Waite, Lindsay L.; Waldenberger, Melanie; Wennauer, Roman; Wilkens, Lynne R.; Willenborg, Christina; Wilsgaard, Tom; Wojczynski, Mary K.; Wong, Andrew; Wright, Alan F.; Zhang, Qunyuan; Arveiler, Dominique; Bakker, Stephan J. L.; Beilby, John; Bergman, Richard N.; Bergmann, Sven; Biffar, Reiner; Blangero, John; Boomsma, I.; Bornstein, Stefan R.; Bovet, Pascal; Brambilla, Paolo; Brown, Morris J.; Campbell, Harry; Caulfield, Mark J.; Chakravarti, Aravinda; Collins, Rory; Collins, Francis S.; Crawford, Dana C.; Cupples, L. Adrienne; Danesh, John; de Faire, Ulf; den Ruijter, Hester M.; Erbel, Raimund; Erdmann, Jeanette; Eriksson, Johan G.; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Ford, Ian; Forouhi, Nita G.; Forrester, Terrence; Gansevoort, Ron T.; Gejman, Pablo V.; Gieger, Christian; Golay, Alain; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Haas, David W.; Hall, Alistair S.; Harris, Tamara B.; Hattersley, Andrew T.; Heath, Andrew C.; Hengstenberg, Christian; Hicks, Andrew A.; Hindorff, Lucia A.; Hingorani, Aroon D.; Hofman, Albert; Hovingh, G. Kees; Humphries, Steve E.; Hunt, Steven C.; Hypponen, Elina; Jacobs, Kevin B.; Jarvelin, Marjo-Riitta; Jousilahti, Pekka; Jula, Antti M.; Kaprio, Jaakko; Kastelein, John J. P.; Kayser, Manfred; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M.; Kiemeney, Lambertus A.; Kooner, Jaspal S.; Kooperberg, Charles; Koskinen, Seppo; Kovacs, Peter; Kraja, Aldi T.; Kumari, Meena; Kuusisto, Johanna; Lakka, Timo A.; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lupoli, Sara; Madden, Pamela A. F.; Männistö, Satu; Manunta, Paolo; Marette, André; Matise, Tara C.; McKnight, Barbara; Meitinger, Thomas; Moll, Frans L.; Montgomery, Grant W.; Morris, Andrew D.; Morris, Andrew P.; Murray, Jeffrey C.; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J.; Ong, Ken K.; Ouwehand, Willem H.; Pasterkamp, Gerard; Peters, Annette; Pramstaller, Peter P.; Price, Jackie F.; Qi, Lu; Raitakari, Olli T.; Rankinen, Tuomo; Rao, D. C.; Rice, Treva K.; Ritchie, Marylyn; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J.; Saramies, Jouko; Sarzynski, Mark A.; Schwarz, Peter E. H.; Sebert, Sylvain; Sever, Peter; Shuldiner, Alan R.; Sinisalo, Juha; Steinthorsdottir, Valgerdur; Stolk, Ronald P.; Tardif, Jean-Claude; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Virtamo, Jarmo; Vohl, Marie-Claude; Amouyel, Philippe; Asselbergs, Folkert W.; Assimes, Themistocles L.; Bochud, Murielle; Boehm, Bernhard O.; Boerwinkle, Eric; Bottinger, Erwin P.; Bouchard, Claude; Cauchi, Stéphane; Chambers, John C.; Chanock, Stephen J.; Cooper, Richard S.; de Bakker, Paul I. W.; Dedoussis, George; Ferrucci, Luigi; Franks, Paul W.; Froguel, Philippe; Groop, Leif C.; Haiman, Christopher A.; Hamsten, Anders; Hayes, M. Geoffrey; Hui, Jennie; Hunter, David J.; Hveem, Kristian; Jukema, J. Wouter; Kaplan, Robert C.; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; Martin, Nicholas G.; März, Winfried; Melbye, Mads; Moebus, Susanne; Munroe, Patricia B.; Njølstad, Inger; Oostra, Ben A.; Palmer, Colin N. A.; Pedersen, Nancy L.; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Powell, Joseph E.; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Reinmaa, Eva; Ridker, Paul M.; Rivadeneira, Fernando; Rotter, Jerome I.; Saaristo, Timo E.; Saleheen, Danish; Schlessinger, David; Slagboom, P. Eline; Snieder, Harold; Spector, Tim D.; Strauch, Konstantin; Stumvoll, Michael; Tuomilehto, Jaakko; Uusitupa, Matti; van der Harst, Pim; Völzke, Henry; Walker, Mark; Wareham, Nicholas J.; Watkins, Hugh; Wichmann, H.-Erich; Wilson, James F.; Zanen, Pieter; Deloukas, Panos; Heid, Iris M.; Lindgren, Cecilia M.; Mohlke, Karen L.; Thorsteinsdottir, Unnur; Barroso, Inês; Fox, Caroline S.; North, Kari E.; Strachan, David P.; Beckmann, Jacques S.; Berndt, Sonja I.; Borecki, Ingrid B.; McCarthy, Mark I.; Metspalu, Andres; Stefansson, Kari; Uitterlinden, André G.; van Duijn, Cornelia M.; Willer, Cristen J.; Price, Alkes L.; Lettre, Guillaume; Loos, Ruth J. F.; Weedon, Michael N.; Ingelsson, Erik; O'Connell, Jeffrey R.; Abecasis, Goncalo R.; Chasman, Daniel I.; Goddard, Michael E.; Visscher, Peter M.; Frayling, Timothy M.

    2015-01-01

    The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated

  3. Expanding Internal Control Functionality Scope

    Directory of Open Access Journals (Sweden)

    Mykola M. Vuitsiv

    2012-08-01

    Full Text Available The article reviews the influence of «western» concepts of the information needs of management process provisions on forming and developing the up-to-date model of Internal Control. An attempt has been made to develop the approach to solve urgent management tasks by applying the ideas of controlling and management accounting via the traditional national approach to the content of control. The place of control in the enterprise management information system has also been reviewed.

  4. A biologically inspired psychometric function for accuracy of visual identification as a function of exposure duration

    DEFF Research Database (Denmark)

    Petersen, Anders; Andersen, Tobias

    The psychometric function of letter identification is typically described as a function of stimulus intensity. However, the effect of stimulus exposure duration on letter identification remains poorly described. This is surprising because the effect of exposure duration has played a central role ...

  5. How to use individual differences to isolate functional organization, biology, and utility of visual functions; with illustrative proposals for stereopsis

    Science.gov (United States)

    Wilmer, Jeremy B.

    2008-01-01

    This paper is a call for greater use of individual differences in the basic science of visual perception. Individual differences yield insights into visual perception’s functional organization, underlying biological/environmental mechanisms, and utility. I first explain the general approach advocated and where it comes from. Second, I describe five principles central to learning about the nature of visual perception through individual differences. Third, I elaborate on the use of individual differences to gain insights into the three areas mentioned above (function, biology/environment, utility), in each case describing the approach advocated, presenting model examples from the literature, and laying out illustrative research proposals for the case of stereopsis. PMID:19017483

  6. Electronic-nuclear entanglement in H2 +: Schmidt decomposition of non-Born-Oppenheimer wave functions expanded in nonorthogonal basis sets

    Science.gov (United States)

    Sanz-Vicario, José Luis; Pérez-Torres, Jhon Fredy; Moreno-Polo, Germán

    2017-08-01

    We compute the entanglement between the electronic and vibrational motions in the simplest molecular system, the hydrogen molecular ion, considering the molecule as a bipartite system, electron and vibrational motion. For that purpose we compute an accurate total non-Born-Oppenheimer wave function in terms of a huge expansion using nonorthogonal B-spline basis sets that expand separately the electronic and nuclear wave functions. According to the Schmidt decomposition theorem for bipartite systems, widely used in quantum-information theory, it is possible to find a much shorter but equivalent expansion in terms of the natural orbitals or Schmidt bases for the electronic and nuclear half spaces. Here we extend the Schmidt decomposition theorem to the case in which nonorthogonal bases are used to span the partitioned Hilbert spaces. This extension is first illustrated with two simple coupled systems, the former without an exact solution and the latter exactly solvable. In these model systems of distinguishable coupled particles it is shown that the entanglement content does not increase monotonically with the excitation energy, but only within the manifold of states that belong to an existing excitation mode, if any. In the hydrogen molecular ion the entanglement content for each non-Born-Oppenheimer vibronic state is quantified through the von Neumann and linear entropies and we show that entanglement serves as a witness to distinguish vibronic states related to different Born-Oppenheimer molecular energy curves or electronic excitation modes.

  7. Functional Genomics Assistant (FUGA: a toolbox for the analysis of complex biological networks

    Directory of Open Access Journals (Sweden)

    Ouzounis Christos A

    2011-10-01

    Full Text Available Abstract Background Cellular constituents such as proteins, DNA, and RNA form a complex web of interactions that regulate biochemical homeostasis and determine the dynamic cellular response to external stimuli. It follows that detailed understanding of these patterns is critical for the assessment of fundamental processes in cell biology and pathology. Representation and analysis of cellular constituents through network principles is a promising and popular analytical avenue towards a deeper understanding of molecular mechanisms in a system-wide context. Findings We present Functional Genomics Assistant (FUGA - an extensible and portable MATLAB toolbox for the inference of biological relationships, graph topology analysis, random network simulation, network clustering, and functional enrichment statistics. In contrast to conventional differential expression analysis of individual genes, FUGA offers a framework for the study of system-wide properties of biological networks and highlights putative molecular targets using concepts of systems biology. Conclusion FUGA offers a simple and customizable framework for network analysis in a variety of systems biology applications. It is freely available for individual or academic use at http://code.google.com/p/fuga.

  8. PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes.

    Science.gov (United States)

    Gupte, Rebecca; Liu, Ziying; Kraus, W Lee

    2017-01-15

    The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates. Supporting these advances is a host of methodological approaches from chemical biology, proteomics, genomics, cell biology, and genetics that have propelled new discoveries in the field. New findings on the diverse roles of PARPs in chromatin regulation, transcription, RNA biology, and DNA repair have been complemented by recent advances that link ADP-ribosylation to stress responses, metabolism, viral infections, and cancer. These studies have begun to reveal the promising ways in which PARPs may be targeted therapeutically for the treatment of disease. In this review, we discuss these topics and relate them to the future directions of the field. © 2017 Gupte et al.; Published by Cold Spring Harbor Laboratory Press.

  9. To be well - to function well. Health biology at Copenhagen University

    DEFF Research Database (Denmark)

    Rosenkilde, Per

    1995-01-01

    Human Fysiologi, Health biology, Public health, Biology Curriculum, University curriculum, Health promotion.......Human Fysiologi, Health biology, Public health, Biology Curriculum, University curriculum, Health promotion....

  10. Watering, fertilization, and slurry inoculation promote recovery of biological crust function in degraded soils.

    Science.gov (United States)

    Maestre, Fernando T; Martín, Noelia; Díez, Beatriz; López-Poma, Rosario; Santos, Fernando; Luque, Ignacio; Cortina, Jordi

    2006-10-01

    Biological soil crusts are very sensitive to human-induced disturbances and are in a degraded state in many areas throughout their range. Given their importance in the functioning of arid and semiarid ecosystems, restoring these crusts may contribute to the recovery of ecosystem functionality in degraded areas. We conducted a factorial microcosm experiment to evaluate the effects of inoculation type (discrete fragments vs slurry), fertilization (control vs addition of composted sewage sludge), and watering frequency (two vs five times per week) on the cyanobacterial composition, nitrogen fixation, chlorophyll content, and net CO2 exchange rate of biological soil crusts inoculated on a semiarid degraded soil from SE Spain. Six months after the inoculation, the highest rates of nitrogen fixation and chlorophyll a content were found when the biological crusts were inoculated as slurry, composted sewage sludge was added, and the microcosms were watered five times per week. Net CO2 exchange rate increased when biological crusts were inoculated as slurry and the microcosms were watered five times per week. Denaturing gradient gel electrophoresis fingerprints and phylogenetic analyses indicated that most of the cyanobacterial species already present in the inoculated crust had the capability to spread and colonize the surface of the surrounding soil. These analyses showed that cyanobacterial communities were less diverse when the microcosms were watered five times per week, and that watering frequency (followed in importance by the addition of composted sewage sludge and inoculation type) was the treatment that most strongly influenced their composition. Our results suggest that the inoculation of biological soil crusts in the form of slurry combined with the addition of composted sewage sludge could be a suitable technique to accelerate the recovery of the composition and functioning of biological soil crusts in drylands.

  11. An overview of the applicability of functional diversity in Biological Conservation

    Directory of Open Access Journals (Sweden)

    J. R. Freitas

    2017-10-01

    Full Text Available Abstract Functional diversity is increasingly pointed as a useful approach to reach Biological Conservation goals. Here, we provide an overview of the functional diversity approach status in the Biological Conservation field. We sought for peer-reviewed papers published over a period of twenty years (from 1994 to 2014. First we used the general topic “functional diversity” and then refined our search using the key-word “conservation”. We have identified the conservation strategies addressed, the organism studied, and the continent of study site in each paper. Thirteen classes of conservation strategies were identified. Plants were the most commonly studied organism group and most study-sites were located in Europe. The functional diversity approach was introduced in the Biological Conservation field in the early 2000’s and its inclusion in conservation strategies is broadly advised. However, the number of papers that operationalise such inclusion by developing models and systems is still low. Functional diversity responds differently and eventually better than other measures to changes in land use and management, which suggests that this approach can potentially better predict the impacts. More studies are needed to corroborate this hypothesis. We pointed out knowledge gaps regarding identification of the responses for functional diversity about urban impacts and in research on the level of management intensity of land needed to maintain functional diversity. We recommend the use of functional diversity measures to find ecological indicators. Future studies should focus on the development of functional diversity measures of other taxa beyond plants as well as test hypothesis in tropical ecosystems.

  12. Develop Infrared Structural Biology for Probing Structural Dynamics of Protein Functions

    Science.gov (United States)

    Xie, Aihua; Kang, Zhouyang; Causey, Oliver; Liu, Charle

    2015-03-01

    Protein functions are carried out through a series of structural transitions. Lack of knowledge on functionally important structural motions of proteins impedes our understanding of protein functions. Infrared structural biology is an emerging technology with powerful applications for protein structural dynamics. One key element of infrared structural biology is the development of vibrational structural marker (VSM) database library that translates infrared spectroscopic signals into specific structural information. We report the development of VSM for probing the type, geometry and strength of hydrogen bonding interactions of buried COO- side chains of Asp and Glu in proteins. Quantum theory based first principle computational studies combined with bioinformatic hydrogen bond analysis are employed in this study. We will discuss the applications of VSM in mechanistic studies of protein functions. Infrared structural biology is expected to emerge as a powerful technique for elucidating the functional mechanism of a broad range of proteins, including water soluble and membrane proteins. This work is supported by OCAST HR10-078 and NSF DBI1338097.

  13. Inverse treatment planning by physically constrained minimization of a biological objective function.

    Science.gov (United States)

    Stavrev, P; Hristov, D; Warkentin, B; Sham, E; Stavreva, N; Fallone, B G

    2003-11-01

    In the current state-of-the art of clinical inverse planning, the design of clinically acceptable IMRT plans is predominantly based on the optimization of physical rather than biological objective functions. A major impetus for this trend is the unproven predictive power of radiobiological models, which is largely due to the scarcity of data sets for an accurate evaluation of the model parameters. On the other hand, these models do capture the currently known dose-volume effects in tissue dose-response, which should be accounted for in the process of optimization. In order to incorporate radiobiological information in clinical treatment planning optimization, we propose a hybrid physico-biological approach to inverse treatment planning based on the application of a continuous penalty function method to the constrained minimization of a biological objective. The objective is defined as the weighted sum of normal tissue complication probabilities evaluated with the Lyman normal-tissue complication probability model. Physical constraints specify the admissible minimum and maximum target dose. The continuous penalty function method is then used to find an approximate solution of the resulting large-scale constrained minimization problem. Plans generated by our approach are compared to ones produced by a commercial planning system incorporating physical optimization. The comparisons show clinically negligible differences, with the advantage that the hybrid technique does not require specifications of any dose-volume constraints to the normal tissues. This indicates that the proposed hybrid physico-biological method can be used for the generation of clinically acceptable plans.

  14. Potential applications of metagenomics to assess the biological effects of food structure and function.

    Science.gov (United States)

    Santiago-Rodriguez, Tasha M; Cano, Raul; Jiménez-Flores, Rafael

    2016-10-12

    Metagenomics, or the collective study of genomes is an important emerging area in microbiology and related fields, and is increasingly being recognized as a tool to characterize the microbial community structure and function of diverse sample types. Metagenomics compares sequences to existing databases to enable the identification of potential microbial reservoirs and predict specific functions; yet, metagenomics has not been widely applied to understand how changes in the food structure and composition affect microbial communities and their function in the human gut. Studies are needed to understand the digestion of food products, and to measure their effectiveness in preserving a healthy microbiome, as well as intestinal function. We suggest the use of metagenomics with validation techniques such as Polymerase Chain Reaction (PCR), cloning and functional assays to assess the biological effects of food structure and function.

  15. Enhanced Biological Functions of Human Mesenchymal Stem-Cell Aggregates Incorporating E-Cadherin-Modified PLGA Microparticles.

    Science.gov (United States)

    Zhang, Yan; Mao, Hongli; Gao, Chao; Li, Suhua; Shuai, Qizhi; Xu, Jianbin; Xu, Ke; Cao, Lei; Lang, Ren; Gu, Zhongwei; Akaike, Toshihiro; Yang, Jun

    2016-08-01

    Mesenchymal stem cells (MSCs) have emerged as a promising source of multipotent cells for various cell-based therapies due to their unique properties, and formation of 3D MSC aggregates has been explored as a potential strategy to enhance therapeutic efficacy. In this study, poly(lactic-co-glycolic acid) (PLGA) microparticles modified with human E-cadherin fusion protein (hE-cad-PLGA microparticles) have been fabricated and integrated with human MSCs to form 3D cell aggregates. The results show that, compared with the plain PLGA, the hE-cad-PLGA microparticles distribute within the aggregates more evenly and further result in a more significant improvement of cellular proliferation and secretion of a series of bioactive factors due to the synergistic effects from the bioactive E-cadherin fragments and the PLGA microparticles. Meanwhile, the hE-cad-PLGA microparticles incorporated in the aggregates upregulate the phosphorylation of epidermal growth factor receptors and activate the AKT and ERK1/2 signaling pathways in the MSCs. Additionally, the E-cadherin/β-catenin cellular membrane complex in the MSCs is markedly stimulated by the hE-cad-PLGA microparticles. Therefore, engineering 3D cell aggregates with hE-cad-PLGA microparticles can be a promising method for ex vivo multipotent stem-cell expansion with enhanced biological functions and may offer a novel route to expand multipotent stem-cell-based clinical applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Hypothermic machine perfusion reduces delayed graft function and improves one-year graft survival of kidneys from expanded criteria donors: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Baoping Jiao

    Full Text Available BACKGROUND: Expanded criteria donors (ECDs are currently accepted as potential sources to increase the donor pool and to provide more chances of kidney transplantation for elderly recipients who would not survive long waiting periods. Hypothermic machine perfusion (HMP is designed to mitigate the deleterious effects of simple cold storage (CS on the quality of preserved organs, particularly when the donor is in a marginal status. METHODS: We compared the transplant outcomes in patients receiving ECD kidneys with either HMP or CS graft preservation. Articles from the MEDLINE, EMBASE and Cochrane Library databases were searched and all studies reporting outcomes from HMP versus CS methods of kidney preservation were included in this meta-analysis. The parameters analyzed included the incidence of delayed graft function (DGF, primary non-function (PNF and one-year graft and patient survival. RESULTS: A total of seven studies qualified for the review, involving 2374 and 8716 kidney grafts with HMP or CS preservation respectively, all from ECD donors. The incidence of delayed graft function (DGF was significantly reduced with an odd ratio(OR of 0.59 (95% CI 0.54-0.66, P<0.001 and one-year graft survival was significantly improved with an OR of 1.12 (95% CI 1.03-1.21, P = 0.005 in HMP preservation compared to CS. However, there was no difference in the incidence of PNF (OR 0.54, 95% CI 0.21-1.40, P = 0.20, and one-year patient survival (OR 0.98, 95% CI 0.94-1.02, P = 0.36 between HMP and CS preservation. CONCLUSIONS: HMP was associated with a reduced incidence of DGF and an with increased one-year graft survival, but it was not associated with the incidence of PNF and one-year patient survival.

  17. Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy.

    Science.gov (United States)

    Hollyman, Daniel; Stefanski, Jolanta; Przybylowski, Mark; Bartido, Shirley; Borquez-Ojeda, Oriana; Taylor, Clare; Yeh, Raymond; Capacio, Vanessa; Olszewska, Malgorzata; Hosey, James; Sadelain, Michel; Brentjens, Renier J; Rivière, Isabelle

    2009-01-01

    On the basis of promising preclinical data demonstrating the eradication of systemic B-cell malignancies by CD19-targeted T lymphocytes in vivo in severe combined immunodeficient-beige mouse models, we are launching phase I clinical trials in patients with chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia. We present here the validation of the bioprocess which we developed for the production and expansion of clinical grade autologous T cells derived from patients with CLL. We demonstrate that T cells genetically modified with a replication-defective gammaretroviral vector derived from the Moloney murine leukemia virus encoding a chimeric antigen receptor (CAR) targeted to CD19 (1928z) can be expanded with Dynabeads CD3/CD28. This bioprocess allows us to generate clinical doses of 1928z+ T cells in approximately 2 to 3 weeks in a large-scale semiclosed culture system using the Wave Bioreactor. These 1928z+ T cells remain biologically functional not only in vitro but also in severe combined immunodeficient-beige mice bearing disseminated tumors. The validation requirements in terms of T-cell expansion, T-cell transduction with the 1928z CAR, biologic activity, quality control testing, and release criteria were met for all 4 validation runs using apheresis products from patients with CLL. Additionally, after expansion of the T cells, the diversity of the skewed Vbeta T-cell receptor repertoire was significantly restored. This validated process will be used in phase I clinical trials in patients with chemorefractory CLL and in patients with relapsed acute lymphoblastic leukemia. It can also be adapted for other clinical trials involving the expansion and transduction of patient or donor T cells using any CAR or T-cell receptor.

  18. Detection of structural and functional changes in biological materials using angle-resolved low coherence interferometry

    Science.gov (United States)

    Chalut, Kevin J.; Ostrander, Julie H.; Wax, Adam

    2008-02-01

    A well-established method of assessing structure is inverse light scattering analysis. With inverse light scattering analysis, the measured scattering properties of a scatterer(s) are associated with the most probable scattering distribution predicted by an appropriate light scattering model. One commonly used light scattering model is Mie theory, the electromagnetic theory of spherical scattering. Although Mie theory is a spherical scattering model, it has been used for deducing the geometry of spheroidal scatterers, which are important for studies of biological cell structure. The angle-resolved low coherence interferometry (a/LCI) technique is one method of Mie theory - based inverse light scattering analysis that has been used to evaluate biological structure both ex vivo and in vitro. In the present study, we examine the ability of a/LCI to assess structure, geometry, and cellular organization in ways that will further enable the study of function in biological materials.

  19. The bottom-up approach to defining life : deciphering the functional organization of biological cells via multi-objective representation of biological complexity from molecules to cells

    Directory of Open Access Journals (Sweden)

    Sathish ePeriyasamy

    2013-12-01

    Full Text Available In silico representation of cellular systems needs to represent the adaptive dynamics of biological cells, recognizing a cell’s multi-objective topology formed by spatially and temporally cohesive intracellular structures. The design of these models needs to address the hierarchical and concurrent nature of cellular functions and incorporate the ability to self-organise in response to transitions between healthy and pathological phases, and adapt accordingly. The functions of biological systems are constantly evolving, due to the ever changing demands of their environment. Biological systems meet these demands by pursuing objectives, aided by their constituents, giving rise to biological functions. A biological cell is organised into an objective/task hierarchy. These objective hierarchy corresponds to the nested nature of temporally cohesive structures and representing them will facilitate in studying pleiotropy and polygeny by modeling causalities propagating across multiple interconnected intracellular processes. Although biological adaptations occur in physiological, developmental and reproductive timescales, the paper is focused on adaptations that occur within physiological timescales, where the biomolecular activities contributing to functional organisation, play a key role in cellular physiology. The paper proposes a multi-scale and multi-objective modelling approach from the bottom-up by representing temporally cohesive structures for multi-tasking of intracellular processes. Further the paper characterises the properties and constraints that are consequential to the organisational and adaptive dynamics in biological cells.

  20. Immune function parameters as markers of biological age and predictors of longevity

    Science.gov (United States)

    de Toda, Irene Martínez; Maté, Ianire; Vida, Carmen; Cruces, Julia; De la Fuente, Mónica

    2016-01-01

    Chronological age is not a good indicator of how each individual ages and thus how to maintain good health. Due to the long lifespan in humans and the consequent difficulty of carrying out longitudinal studies, finding valid biomarkers of the biological age has been a challenge both for research and clinical studies. The aim was to identify and validate several immune cell function parameters as markers of biological age. Adult, mature, elderly and long-lived human volunteers were used. The chemotaxis, phagocytosis, natural killer activity and lymphoproliferation in neutrophils and lymphocytes of peripheral blood were analyzed. The same functions were measured in peritoneal immune cells from mice, at the corresponding ages (adult, mature, old and long lived) in a longitudinal study. The results showed that the evolution of these functions was similar in humans and mice, with a decrease in old subjects. However, the long-lived individuals maintained values similar to those in adults. In addition, the values of these functions in adult prematurely aging mice were similar to those in chronologically old animals, and they died before their non-prematurely aging mice counterparts. Thus, the parameters studied are good markers of the rate of aging, allowing the determination of biological age. PMID:27899767

  1. Mesenchymal stem cells expanded in human platelet lysate display a decreased inhibitory capacity on T- and NK-cell proliferation and function.

    Science.gov (United States)

    Abdelrazik, Heba; Spaggiari, Grazia M; Chiossone, Laura; Moretta, Lorenzo

    2011-11-01

    The use of fetal bovine serum (FBS) for the culture and expansion of mesenchymal stromal cells (MSCs) limits their possible clinical applications. Although some recent studies recommended substituting FBS with human platelet lysate (HPL) for the expansion of MSCs for clinical use, the functional capacity of the expanded cells has only been partially explored. 10% FBS and two other commercial FBS-containing media (MesenCult and MesenPro) were compared with 10% HPL-containing medium for their ability to support MSCs expansion and immunomodulation. We demonstrate that HPL sustained MSC proliferation and expansion in vitro. However, the cumulative cell numbers recovered were comparable with those obtained in MesenPro medium. Moreover, we show that HPL alters the expression of some relevant MSC surface molecules, namely the DNAM-1 ligands PVR and Nectin-2, the NKG2D ligand ULBP3, the adhesion molecules CD49d and αvβ3 and the fibroblast-associated protein. In addition, MSCs cultured in HPL displayed impaired inhibitory capacity on T-cell proliferation to alloantigen and NK-cell proliferation and cytotoxicity. Finally, they showed decreased constitutive PGE2 production while IL-6, IL-8 and RANTES secretion were upregulated. These results imply some limitations in the use of HPL for the expansion of MSCs to be used as immunomodulators in clinical applications. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. The Widespread Prevalence and Functional Significance of Silk-Like Structural Proteins in Metazoan Biological Materials.

    Directory of Open Access Journals (Sweden)

    Carmel McDougall

    Full Text Available In nature, numerous mechanisms have evolved by which organisms fabricate biological structures with an impressive array of physical characteristics. Some examples of metazoan biological materials include the highly elastic byssal threads by which bivalves attach themselves to rocks, biomineralized structures that form the skeletons of various animals, and spider silks that are renowned for their exceptional strength and elasticity. The remarkable properties of silks, which are perhaps the best studied biological materials, are the result of the highly repetitive, modular, and biased amino acid composition of the proteins that compose them. Interestingly, similar levels of modularity/repetitiveness and similar bias in amino acid compositions have been reported in proteins that are components of structural materials in other organisms, however the exact nature and extent of this similarity, and its functional and evolutionary relevance, is unknown. Here, we investigate this similarity and use sequence features common to silks and other known structural proteins to develop a bioinformatics-based method to identify similar proteins from large-scale transcriptome and whole-genome datasets. We show that a large number of proteins identified using this method have roles in biological material formation throughout the animal kingdom. Despite the similarity in sequence characteristics, most of the silk-like structural proteins (SLSPs identified in this study appear to have evolved independently and are restricted to a particular animal lineage. Although the exact function of many of these SLSPs is unknown, the apparent independent evolution of proteins with similar sequence characteristics in divergent lineages suggests that these features are important for the assembly of biological materials. The identification of these characteristics enable the generation of testable hypotheses regarding the mechanisms by which these proteins assemble and direct the

  3. TCA Cycle and Mitochondrial Membrane Potential Are Necessary for Diverse Biological Functions.

    Science.gov (United States)

    Martínez-Reyes, Inmaculada; Diebold, Lauren P; Kong, Hyewon; Schieber, Michael; Huang, He; Hensley, Christopher T; Mehta, Manan M; Wang, Tianyuan; Santos, Janine H; Woychik, Richard; Dufour, Eric; Spelbrink, Johannes N; Weinberg, Samuel E; Zhao, Yingming; DeBerardinis, Ralph J; Chandel, Navdeep S

    2016-01-21

    Mitochondrial metabolism is necessary for the maintenance of oxidative TCA cycle function and mitochondrial membrane potential. Previous attempts to decipher whether mitochondria are necessary for biological outcomes have been hampered by genetic and pharmacologic methods that simultaneously disrupt multiple functions linked to mitochondrial metabolism. Here, we report that inducible depletion of mitochondrial DNA (ρ(ο) cells) diminished respiration, oxidative TCA cycle function, and the mitochondrial membrane potential, resulting in diminished cell proliferation, hypoxic activation of HIF-1, and specific histone acetylation marks. Genetic reconstitution only of the oxidative TCA cycle function specifically in these inducible ρ(ο) cells restored metabolites, resulting in re-establishment of histone acetylation. In contrast, genetic reconstitution of the mitochondrial membrane potential restored ROS, which were necessary for hypoxic activation of HIF-1 and cell proliferation. These results indicate that distinct mitochondrial functions associated with respiration are necessary for cell proliferation, epigenetics, and HIF-1 activation. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Multilevel functional genomics data integration as a tool for understanding physiology: a network biology perspective.

    Science.gov (United States)

    Davidsen, Peter K; Turan, Nil; Egginton, Stuart; Falciani, Francesco

    2016-02-01

    The overall aim of physiological research is to understand how living systems function in an integrative manner. Consequently, the discipline of physiology has since its infancy attempted to link multiple levels of biological organization. Increasingly this has involved mathematical and computational approaches, typically to model a small number of components spanning several levels of biological organization. With the advent of "omics" technologies, which can characterize the molecular state of a cell or tissue (intended as the level of expression and/or activity of its molecular components), the number of molecular components we can quantify has increased exponentially. Paradoxically, the unprecedented amount of experimental data has made it more difficult to derive conceptual models underlying essential mechanisms regulating mammalian physiology. We present an overview of state-of-the-art methods currently used to identifying biological networks underlying genomewide responses. These are based on a data-driven approach that relies on advanced computational methods designed to "learn" biology from observational data. In this review, we illustrate an application of these computational methodologies using a case study integrating an in vivo model representing the transcriptional state of hypoxic skeletal muscle with a clinical study representing muscle wasting in chronic obstructive pulmonary disease patients. The broader application of these approaches to modeling multiple levels of biological data in the context of modern physiology is discussed. Copyright © 2016 the American Physiological Society.

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

    Science.gov (United States)

    Zammito, John

    2006-12-01

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

  6. High performance hybrid functional Petri net simulations of biological pathway models on CUDA.

    Science.gov (United States)

    Chalkidis, Georgios; Nagasaki, Masao; Miyano, Satoru

    2011-01-01

    Hybrid functional Petri nets are a wide-spread tool for representing and simulating biological models. Due to their potential of providing virtual drug testing environments, biological simulations have a growing impact on pharmaceutical research. Continuous research advancements in biology and medicine lead to exponentially increasing simulation times, thus raising the demand for performance accelerations by efficient and inexpensive parallel computation solutions. Recent developments in the field of general-purpose computation on graphics processing units (GPGPU) enabled the scientific community to port a variety of compute intensive algorithms onto the graphics processing unit (GPU). This work presents the first scheme for mapping biological hybrid functional Petri net models, which can handle both discrete and continuous entities, onto compute unified device architecture (CUDA) enabled GPUs. GPU accelerated simulations are observed to run up to 18 times faster than sequential implementations. Simulating the cell boundary formation by Delta-Notch signaling on a CUDA enabled GPU results in a speedup of approximately 7x for a model containing 1,600 cells.

  7. Effector Biology in Focus: A Primer for Computational Prediction and Functional Characterization.

    Science.gov (United States)

    Dalio, Ronaldo J D; Herlihy, John; Oliveira, Tiago S; McDowell, John M; Machado, Marcos

    2018-01-01

    Plant-pathogen interactions are controlled by a multilayered immune system, which is activated by pathogen recognition in the host. Pathogens secrete effector molecules to interfere with the immune recognition or signaling network and reprogram cell structure or metabolism. Understanding the effector repertoires of diverse pathogens will contribute to unraveling the molecular mechanism of virulence and developing sustainable disease-control strategies for crops and natural ecosystems. Effector functionality has been investigated extensively in only a small number of pathogen species. However, many more pathogen genomes are becoming available, and much can be learned from a broader view of effector biology in diverse pathosystems. The purpose of this review is to summarize methodology for computational prediction of protein effectors, functional characterization of effector proteins and their targets, and the use of effectors as probes to screen for new sources of host resistance. Although these techniques were generally developed in model pathosystems, many of the approaches are directly applicable for exploration and exploitation of effector biology in pathosystems that are less well studied. We hope to facilitate such exploration, which will broaden understanding of the mechanisms that underpin the biological diversity of plant-pathogen interactions, and maximize the impact of new approaches that leverage effector biology for disease control.

  8. Molecular Characteristics and Biological Functions of Surface-Active and Surfactant Proteins.

    Science.gov (United States)

    Sunde, Margaret; Pham, Chi L L; Kwan, Ann H

    2017-06-20

    Many critical biological processes take place at hydrophobic:hydrophilic interfaces, and a wide range of organisms produce surface-active proteins and peptides that reduce surface and interfacial tension and mediate growth and development at these boundaries. Microorganisms produce both small lipid-associated peptides and amphipathic proteins that allow growth across water:air boundaries, attachment to surfaces, predation, and improved bioavailability of hydrophobic substrates. Higher-order organisms produce surface-active proteins with a wide variety of functions, including the provision of protective foam environments for vulnerable reproductive stages, evaporative cooling, and gas exchange across airway membranes. In general, the biological functions supported by these diverse polypeptides require them to have an amphipathic nature, and this is achieved by a diverse range of molecular structures, with some proteins undergoing significant conformational change or intermolecular association to generate the structures that are surface active.

  9. PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance

    Science.gov (United States)

    van Oers, Johanna M. M.; Roa, Sergio; Werling, Uwe; Liu, Yiyong; Genschel, Jochen; Sellers, Rani S.; Modrich, Paul; Scharff, Matthew D.; Edelmann, Winfried

    2010-01-01

    The DNA mismatch repair protein PMS2 was recently found to encode a novel endonuclease activity. To determine the biological functions of this activity in mammals, we generated endonuclease-deficient Pms2E702K knock-in mice. Pms2EK/EK mice displayed increased genomic mutation rates and a strong cancer predisposition. In addition, class switch recombination, but not somatic hypermutation, was impaired in Pms2EK/EK B cells, indicating a specific role in Ig diversity. In contrast to Pms2−/− mice, Pms2EK/EK male mice were fertile, indicating that this activity is dispensable in spermatogenesis. Therefore, the PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance and tumor suppression. PMID:20624957

  10. Tongue and Taste Organ Biology and Function: Homeostasis Maintained by Hedgehog Signaling.

    Science.gov (United States)

    Mistretta, Charlotte M; Kumari, Archana

    2017-02-10

    The tongue is an elaborate complex of heterogeneous tissues with taste organs of diverse embryonic origins. The lingual taste organs are papillae, composed of an epithelium that includes specialized taste buds, the basal lamina, and a lamina propria core with matrix molecules, fibroblasts, nerves, and vessels. Because taste organs are dynamic in cell biology and sensory function, homeostasis requires tight regulation in specific compartments or niches. Recently, the Hedgehog (Hh) pathway has emerged as an essential regulator that maintains lingual taste papillae, taste bud and progenitor cell proliferation and differentiation, and neurophysiological function. Activating or suppressing Hh signaling, with genetic models or pharmacological agents used in cancer treatments, disrupts taste papilla and taste bud integrity and can eliminate responses from taste nerves to chemical stimuli but not to touch or temperature. Understanding Hh regulation of taste organ homeostasis contributes knowledge about the basic biology underlying taste disruptions in patients treated with Hh pathway inhibitors.

  11. H2S-Induced Sulfhydration: Biological Function and Detection Methodology

    OpenAIRE

    Da Zhang; Junbao Du; Chaoshu Tang; Yaqian Huang; Hongfang Jin

    2017-01-01

    At appropriate concentrations, hydrogen sulfide, a well-known gasotransmitter, plays important roles in both physiology and pathophysiology. Increasing evidence suggests that modifying thiol groups of specific cysteines in target proteins via sulfhydration or persulfidation is one of the important mechanisms responsible for the biological functions of hydrogen sulfide. A variety of key proteins of different cellular pathways in mammals have been reported to be sulfhydrated by hydrogen sulfide...

  12. Fluctuations observed in biological time series signals and their functional significance.

    Science.gov (United States)

    Yamamoto, M

    1991-01-01

    Fluctuation phenomena in a single neuronal spike train of a cat were investigated during sleep states. Although white-noise-like fluctuations were observed during non-REM sleep, they became 1/f fluctuations during REM sleep. REM sleep is regarded as a reversion to a state of the fetal brain. The functional significance of 1/f fluctuations in biological time series signals is discussed from the viewpoint of homeostasis.

  13. Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges.

    Science.gov (United States)

    Benca, Ruth; Duncan, Marilyn J; Frank, Ellen; McClung, Colleen; Nelson, Randy J; Vicentic, Aleksandra

    2009-12-11

    Increasing evidence suggests that disrupted temporal organization impairs behavior, cognition, and affect; further, disruption of circadian clock genes impairs sleep-wake cycle and social rhythms which may be implicated in mental disorders. Despite this strong evidence, a gap in understanding the neural mechanisms of this interaction obscures whether biological rhythms disturbances are the underlying causes or merely symptoms of mental disorder. Here, we review current understanding, emerging concepts, gaps, and opportunities pertinent to (1) the neurobiology of the interactions between circadian oscillators and the neural circuits subserving higher brain function and behaviors of relevance to mental health, (2) the most promising approaches to determine how biological rhythms regulate brain function and behavior under normal and pathological conditions, (3) the gaps and challenges to advancing knowledge on the link between disrupted circadian rhythms/sleep and psychiatric disorders, and (4) the novel strategies for translation of basic science discoveries in circadian biology to clinical settings to define risk, prevent or delay onset of mental illnesses, design diagnostic tools, and propose new therapeutic strategies. The review is organized around five themes pertinent to (1) the impact of molecular clocks on physiology and behavior, (2) the interactions between circadian signals and cognitive functions, (3) the interface of circadian rhythms with sleep, (4) a clinical perspective on the relationship between circadian rhythm abnormalities and affective disorders, and (5) the pre-clinical models of circadian rhythm abnormalities and mood disorders.

  14. H2S-Induced Sulfhydration: Biological Function and Detection Methodology

    Directory of Open Access Journals (Sweden)

    Da Zhang

    2017-09-01

    Full Text Available At appropriate concentrations, hydrogen sulfide, a well-known gasotransmitter, plays important roles in both physiology and pathophysiology. Increasing evidence suggests that modifying thiol groups of specific cysteines in target proteins via sulfhydration or persulfidation is one of the important mechanisms responsible for the biological functions of hydrogen sulfide. A variety of key proteins of different cellular pathways in mammals have been reported to be sulfhydrated by hydrogen sulfide to participate and regulate the processes of cell survival/death, cell differentiation, cell proliferation/hypertrophy, cellular metabolism, mitochondrial bioenergetics/biogenesis, endoplasmic reticulum stress, vasorelaxtion, inflammation, oxidative stress, etc. Moreover, S-sulfhydration also exerts many biological functions through the cross-talk with other post-translational modifications including phosphorylation, S-nitrosylation and tyrosine nitration. This review summarizes recent studies of hydrogen sulfide-induced sulfhydration as a posttranslational modification, an important biological function of hydrogen sulfide, and sulfhydrated proteins are introduced. Additionally, we discuss the main methods of detecting sulfhydration of proteins.

  15. Paul Langerhans: a prilgrim "traveling" from functional histology to marine biology.

    Science.gov (United States)

    Raica, Marius; Cimpean, Anca Maria

    2017-06-01

    The nineteenth century was the time of a real revolution in science and medicine. A lot of seminal discoveries in medicine and biology were done in this time, and many of them were coincident with the introduction of the compound microscope by Hermann van Deijl and the standard histological technique by Paul Ehrlich. The main tissue types and individual cells were characterized and originally classified more than hundred years ago, although less attention was paid to their basic functions. This was mainly due to the modality of tissue specimen processing that allowed particularly detailed descriptive studies. Even so, we can notice some attempts to correlate the structure with the function. The German scientist Paul Langerhans, well-known for the discovery of Langerhans islets of the pancreas and Langerhans cells from the epidermis, tried to change the conventional fate of morphological studies introducing in his works functional hypothesis based on traditional microscopic observations even from the beginning of his scientific career. Paul Langerhans was a complex personality of the second half of the nineteenth century, not only in medicine, but also in other fields of biology. In the present review, presented is the life and research activity of Paul Langerhans, not only because of the importance of his discoveries, but also for perspectives that were opened by these findings in unexpected fields of medicine and biology.

  16. A Bayesian spatial model for neuroimaging data based on biologically informed basis functions.

    Science.gov (United States)

    Huertas, Ismael; Oldehinkel, Marianne; van Oort, Erik S B; Garcia-Solis, David; Mir, Pablo; Beckmann, Christian F; Marquand, Andre F

    2017-11-01

    The dominant approach to neuroimaging data analysis employs the voxel as the unit of computation. While convenient, voxels lack biological meaning and their size is arbitrarily determined by the resolution of the image. Here, we propose a multivariate spatial model in which neuroimaging data are characterised as a linearly weighted combination of multiscale basis functions which map onto underlying brain nuclei or networks or nuclei. In this model, the elementary building blocks are derived to reflect the functional anatomy of the brain during the resting state. This model is estimated using a Bayesian framework which accurately quantifies uncertainty and automatically finds the most accurate and parsimonious combination of basis functions describing the data. We demonstrate the utility of this framework by predicting quantitative SPECT images of striatal dopamine function and we compare a variety of basis sets including generic isotropic functions, anatomical representations of the striatum derived from structural MRI, and two different soft functional parcellations of the striatum derived from resting-state fMRI (rfMRI). We found that a combination of ∼50 multiscale functional basis functions accurately represented the striatal dopamine activity, and that functional basis functions derived from an advanced parcellation technique known as Instantaneous Connectivity Parcellation (ICP) provided the most parsimonious models of dopamine function. Importantly, functional basis functions derived from resting fMRI were more accurate than both structural and generic basis sets in representing dopamine function in the striatum for a fixed model order. We demonstrate the translational validity of our framework by constructing classification models for discriminating parkinsonian disorders and their subtypes. Here, we show that ICP approach is the only basis set that performs well across all comparisons and performs better overall than the classical voxel-based approach

  17. The Swine Plasma Metabolome Chronicles "Many Days" Biological Timing and Functions Linked to Growth

    Science.gov (United States)

    Bromage, Timothy G.; Idaghdour, Youssef; Lacruz, Rodrigo S.; Crenshaw, Thomas D.; Ovsiy, Olexandra; Rotter, Björn; Hoffmeier, Klaus; Schrenk, Friedemann

    2016-01-01

    The paradigm of chronobiology is based almost wholly upon the daily biological clock, or circadian rhythm, which has been the focus of intense molecular, cellular, pharmacological, and behavioral, research. However, the circadian rhythm does not explain biological timings related to fundamental aspects of life history such as rates of tissue/organ/body size development and control of the timing of life stages such as gestation length, age at maturity, and lifespan. This suggests that another biological timing mechanism is at work. Here we focus on a "many days" (multidien) chronobiological period first observed as enigmatic recurring growth lines in developing mammalian tooth enamel that is strongly associate with all adult tissue, organ, and body masses as well as life history attributes such as gestation length, age at maturity, weaning, and lifespan, particularly among the well studied primates. Yet, knowledge of the biological factors regulating the patterning of mammalian life, such as the development of body size and life history structure, does not exist. To identify underlying molecular mechanisms we performed metabolome and genome analyses from blood plasma in domestic pigs. We show that blood plasma metabolites and small non-coding RNA (sncRNA) drawn from 33 domestic pigs over a two-week period strongly oscillate on a 5-day multidien rhythm, as does the pig enamel rhythm. Metabolomics and genomics pathway analyses actually reveal two 5-day rhythms, one related to growth in which biological functions include cell proliferation, apoptosis, and transcription regulation/protein synthesis, and another 5-day rhythm related to degradative pathways that follows three days later. Our results provide experimental confirmation of a 5-day multidien rhythm in the domestic pig linking the periodic growth of enamel with oscillations of the metabolome and genome. This association reveals a new class of chronobiological rhythm and a snapshot of the biological bases that

  18. System biology approach to detect and assign biological functions and regulator genes to feed efficiency traits in Nellore cattle

    DEFF Research Database (Denmark)

    Alexandre, Pâmela; Kogelman, Lisette; Santana, Miguel

    The objective of this study was to use a system biology approach to identify biological mechanisms involved on feed efficiency in Nellore cattle and its possible regulator genes. Two modules of co-expressed and highly inter-connected genes correlated to feed efficiency were identified as well...

  19. Evaluation of physical and functional protein-protein interaction prediction methods for detecting biological pathways.

    Science.gov (United States)

    Muley, Vijaykumar Yogesh; Ranjan, Akash

    2013-01-01

    Cellular activities are governed by the physical and the functional interactions among several proteins involved in various biological pathways. With the availability of sequenced genomes and high-throughput experimental data one can identify genome-wide protein-protein interactions using various computational techniques. Comparative assessments of these techniques in predicting protein interactions have been frequently reported in the literature but not their ability to elucidate a particular biological pathway. Towards the goal of understanding the prediction capabilities of interactions among the specific biological pathway proteins, we report the analyses of 14 biological pathways of Escherichia coli catalogued in KEGG database using five protein-protein functional linkage prediction methods. These methods are phylogenetic profiling, gene neighborhood, co-presence of orthologous genes in the same gene clusters, a mirrortree variant, and expression similarity. Our results reveal that the prediction of metabolic pathway protein interactions continues to be a challenging task for all methods which possibly reflect flexible/independent evolutionary histories of these proteins. These methods have predicted functional associations of proteins involved in amino acids, nucleotide, glycans and vitamins & co-factors pathways slightly better than the random performance on carbohydrate, lipid and energy metabolism. We also make similar observations for interactions involved among the environmental information processing proteins. On the contrary, genetic information processing or specialized processes such as motility related protein-protein linkages that occur in the subset of organisms are predicted with comparable accuracy. Metabolic pathways are best predicted by using neighborhood of orthologous genes whereas phyletic pattern is good enough to reconstruct central dogma pathway protein interactions. We have also shown that the effective use of a particular prediction

  20. Evaluation of physical and functional protein-protein interaction prediction methods for detecting biological pathways.

    Directory of Open Access Journals (Sweden)

    Vijaykumar Yogesh Muley

    Full Text Available BACKGROUND: Cellular activities are governed by the physical and the functional interactions among several proteins involved in various biological pathways. With the availability of sequenced genomes and high-throughput experimental data one can identify genome-wide protein-protein interactions using various computational techniques. Comparative assessments of these techniques in predicting protein interactions have been frequently reported in the literature but not their ability to elucidate a particular biological pathway. METHODS: Towards the goal of understanding the prediction capabilities of interactions among the specific biological pathway proteins, we report the analyses of 14 biological pathways of Escherichia coli catalogued in KEGG database using five protein-protein functional linkage prediction methods. These methods are phylogenetic profiling, gene neighborhood, co-presence of orthologous genes in the same gene clusters, a mirrortree variant, and expression similarity. CONCLUSIONS: Our results reveal that the prediction of metabolic pathway protein interactions continues to be a challenging task for all methods which possibly reflect flexible/independent evolutionary histories of these proteins. These methods have predicted functional associations of proteins involved in amino acids, nucleotide, glycans and vitamins & co-factors pathways slightly better than the random performance on carbohydrate, lipid and energy metabolism. We also make similar observations for interactions involved among the environmental information processing proteins. On the contrary, genetic information processing or specialized processes such as motility related protein-protein linkages that occur in the subset of organisms are predicted with comparable accuracy. Metabolic pathways are best predicted by using neighborhood of orthologous genes whereas phyletic pattern is good enough to reconstruct central dogma pathway protein interactions. We have also

  1. Hubs of knowledge: using the functional link structure in Biozon to mine for biologically significant entities

    Directory of Open Access Journals (Sweden)

    Isganitis Timothy

    2006-02-01

    Full Text Available Abstract Background Existing biological databases support a variety of queries such as keyword or definition search. However, they do not provide any measure of relevance for the instances reported, and result sets are usually sorted arbitrarily. Results We describe a system that builds upon the complex infrastructure of the Biozon database and applies methods similar to those of Google to rank documents that match queries. We explore different prominence models and study the spectral properties of the corresponding data graphs. We evaluate the information content of principal and non-principal eigenspaces, and test various scoring functions which combine contributions from multiple eigenspaces. We also test the effect of similarity data and other variations which are unique to the biological knowledge domain on the quality of the results. Query result sets are assessed using a probabilistic approach that measures the significance of coherence between directly connected nodes in the data graph. This model allows us, for the first time, to compare different prominence models quantitatively and effectively and to observe unique trends. Conclusion Our tests show that the ranked query results outperform unsorted results with respect to our significance measure and the top ranked entities are typically linked to many other biological entities. Our study resulted in a working ranking system of biological entities that was integrated into Biozon at http://biozon.org.

  2. Hubs of knowledge: using the functional link structure in Biozon to mine for biologically significant entities.

    Science.gov (United States)

    Shafer, Paul; Isganitis, Timothy; Yona, Golan

    2006-02-15

    Existing biological databases support a variety of queries such as keyword or definition search. However, they do not provide any measure of relevance for the instances reported, and result sets are usually sorted arbitrarily. We describe a system that builds upon the complex infrastructure of the Biozon database and applies methods similar to those of Google to rank documents that match queries. We explore different prominence models and study the spectral properties of the corresponding data graphs. We evaluate the information content of principal and non-principal eigenspaces, and test various scoring functions which combine contributions from multiple eigenspaces. We also test the effect of similarity data and other variations which are unique to the biological knowledge domain on the quality of the results. Query result sets are assessed using a probabilistic approach that measures the significance of coherence between directly connected nodes in the data graph. This model allows us, for the first time, to compare different prominence models quantitatively and effectively and to observe unique trends. Our tests show that the ranked query results outperform unsorted results with respect to our significance measure and the top ranked entities are typically linked to many other biological entities. Our study resulted in a working ranking system of biological entities that was integrated into Biozon at http://biozon.org.

  3. Autologous biological pacing function with adrenergic-responsiveness in porcine of complete heart block.

    Science.gov (United States)

    Zhang, Hao; Li, Shuchun; Qu, Dan; Li, Bailing; He, Bin; Wang, Chong; Xu, Zhiyun

    2013-10-09

    To assess the efficacy of autologous biological pacing function by autograft of gene-transferred mesenchymal stem cells in a porcine model of complete heart block. Fourteen healthy young male pigs were randomized into active group (n=8) and control group (n=6). Porcine MSCs were transfected with Ad.HCN4 or Ad.Null. The pacemaker function of transfected MSCs was studied by whole-cell patch clamp. The CHB model of porcine was created with transthoracic ablation technique and the transfected MSCs were autografted into the free wall of right ventricle. The pacing function was studied by ECG and ambulatory Holter recording weekly. The adrenergic responsiveness was evaluated by the variation of heart rate after isoprenaline infusion or food provision following an overnight fasting. HCN4-MSCs expressed a robust time-dependent inward current (If) and the current density of If was 4.3±0.6 pA/pF at -105 mV. In week 2 after autograft, the heart rate of active group became significantly higher than control (53±5 bpm vs. 38±4 bpm, Pheart rate was increased significantly in both groups. However, there was a significant increase of heart rate when presenting food for active group (Pheart rate by providing an adrenergic-responsive biological pacing function, indicating a promising approach without immunological or ethical issues for the treatment of complete heart block. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Automatic extraction of gene/protein biological functions from biomedical text.

    Science.gov (United States)

    Koike, Asako; Niwa, Yoshiki; Takagi, Toshihisa

    2005-04-01

    With the rapid advancement of biomedical science and the development of high-throughput analysis methods, the extraction of various types of information from biomedical text has become critical. Since automatic functional annotations of genes are quite useful for interpreting large amounts of high-throughput data efficiently, the demand for automatic extraction of information related to gene functions from text has been increasing. We have developed a method for automatically extracting the biological process functions of genes/protein/families based on Gene Ontology (GO) from text using a shallow parser and sentence structure analysis techniques. When the gene/protein/family names and their functions are described in ACTOR (doer of action) and OBJECT (receiver of action) relationships, the corresponding GO-IDs are assigned to the genes/proteins/families. The gene/protein/family names are recognized using the gene/protein/family name dictionaries developed by our group. To achieve wide recognition of the gene/protein/family functions, we semi-automatically gather functional terms based on GO using co-occurrence, collocation similarities and rule-based techniques. A preliminary experiment demonstrated that our method has an estimated recall of 54-64% with a precision of 91-94% for actually described functions in abstracts. When applied to the PUBMED, it extracted over 190 000 gene-GO relationships and 150 000 family-GO relationships for major eukaryotes.

  5. Systems Biology-Derived Biomarkers to Predict Progression of Renal Function Decline in Type 2 Diabetes

    DEFF Research Database (Denmark)

    Mayer, Gert; Heerspink, Hiddo J Lambers; Aschauer, Constantin

    2017-01-01

    OBJECTIVE: Chronic kidney disease (CKD) in diabetes has a complex molecular and likely multifaceted pathophysiology. We aimed to validate a panel of biomarkers identified using a systems biology approach to predict the individual decline of estimated glomerular filtration rate (eGFR) in a large...... group of patients with type 2 diabetes and CKD at various stages. RESEARCH DESIGN AND METHODS: We used publicly available "omics" data to develop a molecular process model of CKD in diabetes and identified a representative parsimonious set of nine molecular biomarkers: chitinase 3-like protein 1, growth...... biology approach, combined with clinical variables, enhances the prediction of renal function loss over a wide range of baseline eGFR values in patients with type 2 diabetes and CKD....

  6. Phagekines: Screening Binding Properties and Biological Activity of Functional Cytokines Displayed on Phages.

    Science.gov (United States)

    Rojas, Gertrudis; Carmenate, Tania

    2018-01-01

    The current chapter focuses on the use of filamentous phages to display, modify, and characterize cytokines, which are proteins belonging to a versatile group of essential mediators involved in cell-cell communication. Cytokines exhibit a considerable diversity, both in functions and in structural features underlying their biological effects. A broad variety of cytokines have been successfully displayed on phages, allowing the high-throughput study of their binding properties and biological activities and the discovery of novel therapeutics through directed evolution. The technical singularities and some potential applications of cytokine phage display are illustrated here with the case of Interleukin-2, a prototypic member of the four-alpha-helix bundle cytokine family playing a pivotal role in the immune response and having a long history of therapeutic use.

  7. A Critical Role for Cysteine 57 in the Biological Functions of Selenium Binding Protein-1

    Directory of Open Access Journals (Sweden)

    Qi Ying

    2015-11-01

    Full Text Available The concentration of selenium-binding protein1 (SBP1 is often lower in tumors than in the corresponding tissue and lower levels have been associated with poor clinical outcomes. SBP1 binds tightly selenium although what role selenium plays in its biological functions remains unknown. Previous studies indicated that cysteine 57 is the most likely candidate amino acid for selenium binding. In order to investigate the role of cysteine 57 in SBP1, this amino acid was altered to a glycine and the mutated protein was expressed in human cancer cells. The SBP1 half-life, as well as the cellular response to selenite cytotoxicity, was altered by this change. The ectopic expression of SBP1GLY also caused mitochondrial damage in HCT116 cells. Taken together, these results indicated that cysteine 57 is a critical determinant of SBP1 function and may play a significant role in mitochondrial function.

  8. Efficient randomization of biological networks while preserving functional characterization of individual nodes.

    Science.gov (United States)

    Iorio, Francesco; Bernardo-Faura, Marti; Gobbi, Andrea; Cokelaer, Thomas; Jurman, Giuseppe; Saez-Rodriguez, Julio

    2016-12-20

    Networks are popular and powerful tools to describe and model biological processes. Many computational methods have been developed to infer biological networks from literature, high-throughput experiments, and combinations of both. Additionally, a wide range of tools has been developed to map experimental data onto reference biological networks, in order to extract meaningful modules. Many of these methods assess results' significance against null distributions of randomized networks. However, these standard unconstrained randomizations do not preserve the functional characterization of the nodes in the reference networks (i.e. their degrees and connection signs), hence including potential biases in the assessment. Building on our previous work about rewiring bipartite networks, we propose a method for rewiring any type of unweighted networks. In particular we formally demonstrate that the problem of rewiring a signed and directed network preserving its functional connectivity (F-rewiring) reduces to the problem of rewiring two induced bipartite networks. Additionally, we reformulate the lower bound to the iterations' number of the switching-algorithm to make it suitable for the F-rewiring of networks of any size. Finally, we present BiRewire3, an open-source Bioconductor package enabling the F-rewiring of any type of unweighted network. We illustrate its application to a case study about the identification of modules from gene expression data mapped on protein interaction networks, and a second one focused on building logic models from more complex signed-directed reference signaling networks and phosphoproteomic data. BiRewire3 it is freely available at https://www.bioconductor.org/packages/BiRewire/ , and it should have a broad application as it allows an efficient and analytically derived statistical assessment of results from any network biology tool.

  9. The association between biological rhythms, depression, and functioning in bipolar disorder: a large multi-center study.

    Science.gov (United States)

    Pinho, M; Sehmbi, M; Cudney, L E; Kauer-Sant'anna, M; Magalhães, P V; Reinares, M; Bonnín, C M; Sassi, R B; Kapczinski, F; Colom, F; Vieta, E; Frey, B N; Rosa, A R

    2015-05-22

    We examined the relationship between biological rhythms and severity of depressive symptoms in subjects with bipolar disorder and the effects of biological rhythms alterations on functional impairment. Bipolar patients (n = 260) and healthy controls (n = 191) were recruited from mood disorders programs in three sites (Spain, Brazil, and Canada). Parameters of biological rhythms were measured using the Biological Rhythms Assessment in Neuropsychiatry (BRIAN), an interviewer administered questionnaire that assesses disruptions in sleep, eating patterns, social rhythms, and general activity. Multivariate analyses of covariance showed significant intergroup differences after controlling for potential confounders (Pillai's F = 49.367; df = 2, P biological rhythms disturbance, followed by patients with subsyndromal symptoms, euthymic patients, and healthy controls. Biological rhythms and HAMD scores were independent predictors of poor functioning (F = 12.841, df = 6, P biological rhythms disturbance. Biological rhythms disturbance was also an independent predictor of functional impairment. Although the directionality of this relationship remains unknown, our results suggest that stability of biological rhythms should be an important target of acute and long-term management of bipolar disorder and may aid in the improvement of functioning. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. What Expands in an Expanding Universe?

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    JOSÉ A. DE FREITAS PACHECO

    2015-12-01

    Full Text Available ABSTRACT In the present investigation, the possible effects of the expansion of the Universe on systems bonded either by gravitational or electromagnetic forces, are reconsidered. It will be shown that the acceleration (positive or negative of the expanding background, is the determinant factor affecting planetary orbits and atomic sizes. In the presently accepted cosmology (ΛCDM all bonded systems are expanding at a decreasing rate that tends to be zero as the universe enters in a de Sitter phase. It is worth mentioning that the estimated expansion rates are rather small and they can be neglected for all practical purposes.

  11. What Expands in an Expanding Universe?

    Science.gov (United States)

    Pacheco, José A De Freitas

    2015-01-01

    In the present investigation, the possible effects of the expansion of the Universe on systems bonded either by gravitational or electromagnetic forces, are reconsidered. It will be shown that the acceleration (positive or negative) of the expanding background, is the determinant factor affecting planetary orbits and atomic sizes. In the presently accepted cosmology (ΛCDM) all bonded systems are expanding at a decreasing rate that tends to be zero as the universe enters in a de Sitter phase. It is worth mentioning that the estimated expansion rates are rather small and they can be neglected for all practical purposes.

  12. Correlating novel variable and conserved motifs in the Hemagglutinin protein with significant biological functions

    Directory of Open Access Journals (Sweden)

    Werner Mark

    2008-08-01

    Full Text Available Abstract Background Variations in the influenza Hemagglutinin protein contributes to antigenic drift resulting in decreased efficiency of seasonal influenza vaccines and escape from host immune response. We performed an in silico study to determine characteristics of novel variable and conserved motifs in the Hemagglutinin protein from previously reported H3N2 strains isolated from Hong Kong from 1968–1999 to predict viral motifs involved in significant biological functions. Results 14 MEME blocks were generated and comparative analysis of the MEME blocks identified blocks 1, 2, 3 and 7 to correlate with several biological functions. Analysis of the different Hemagglutinin sequences elucidated that the single block 7 has the highest frequency of amino acid substitution and the highest number of co-mutating pairs. MEME 2 showed intermediate variability and MEME 1 was the most conserved. Interestingly, MEME blocks 2 and 7 had the highest incidence of potential post-translational modifications sites including phosphorylation sites, ASN glycosylation motifs and N-myristylation sites. Similarly, these 2 blocks overlap with previously identified antigenic sites and receptor binding sites. Conclusion Our study identifies motifs in the Hemagglutinin protein with different amino acid substitution frequencies over a 31 years period, and derives relevant functional characteristics by correlation of these motifs with potential post-translational modifications sites, antigenic and receptor binding sites.

  13. Biological and biomedical functions of Penta-O-galloyl-D-glucose and its derivatives.

    Science.gov (United States)

    Cao, Yanyan; Himmeldirk, Klaus B; Qian, Yanrong; Ren, Yulin; Malki, Ahmed; Chen, Xiaozhuo

    2014-07-01

    Penta-O-galloyl-D-glucose (PGG) is a simple hydrolysable tannin in plants. PGG exists in two anomeric forms, α-PGG and β-PGG. While β-PGG can be found in a wide variety of plants, α-PGG is rather rare in nature. Numerous studies with β-PGG revealed a wide variety of biological activities, such as anti-microbial and anti-cancer functions. Until recently, studies with α-PGG were limited by the lack of its availability. Since the development of an efficient chemical synthesis of the compound, several investigations have revealed its anti-diabetic, anti-cancer, and anti-platelet-coagulation functions. Based on structure-activity-relationship (SAR) studies with α-PGG, a variety of α-PGG-related novel compounds were synthesized and some of them have been shown to possess promising therapeutic activities. In this review, the authors will survey and evaluate the biological functions of PGG with a focus on α-PGG and its derivatives.

  14. Integration of multiscale dendritic spine structure and function data into systems biology models

    Directory of Open Access Journals (Sweden)

    James J Mancuso

    2014-11-01

    Full Text Available Comprising 1011 neurons with 1014 synaptic connections the human brain is the ultimate systems biology puzzle. An increasing body of evidence highlights the observation that changes in brain function, both normal and pathological, consistently correlate with dynamic changes in neuronal anatomy. Anatomical changes occur on a full range of scales from the trafficking of individual proteins, to alterations in synaptic morphology both individually and on a systems level, to reductions in long distance connectivity and brain volume. The major sites of contact for synapsing neurons are dendritic spines, which provide an excellent metric for the number and strength of signaling connections between elements of functional neuronal circuits. A comprehensive model of anatomical changes and their functional consequences would be a holy grail for the field of systems neuroscience but its realization appears far on the horizon. Various imaging technologies have advanced to allow for multi-scale visualization of brain plasticity and pathology, but computational analysis of the massive big data sets involved forms the bottleneck toward the creation of multiscale models of brain structure and function. While a full accounting of techniques and progress toward a comprehensive model of brain anatomy and function is beyond the scope of this or any other single paper, this review serves to highlight the opportunities for analysis of neuronal spine anatomy and function provided by new imaging technologies and the high-throughput application of older technologies while surveying the strengths and weaknesses of currently available computational analytical tools and room for future improvement.

  15. Integration of multiscale dendritic spine structure and function data into systems biology models.

    Science.gov (United States)

    Mancuso, James J; Cheng, Jie; Yin, Zheng; Gilliam, Jared C; Xia, Xiaofeng; Li, Xuping; Wong, Stephen T C

    2014-01-01

    Comprising 10(11) neurons with 10(14) synaptic connections the human brain is the ultimate systems biology puzzle. An increasing body of evidence highlights the observation that changes in brain function, both normal and pathological, consistently correlate with dynamic changes in neuronal anatomy. Anatomical changes occur on a full range of scales from the trafficking of individual proteins, to alterations in synaptic morphology both individually and on a systems level, to reductions in long distance connectivity and brain volume. The major sites of contact for synapsing neurons are dendritic spines, which provide an excellent metric for the number and strength of signaling connections between elements of functional neuronal circuits. A comprehensive model of anatomical changes and their functional consequences would be a holy grail for the field of systems neuroscience but its realization appears far on the horizon. Various imaging technologies have advanced to allow for multi-scale visualization of brain plasticity and pathology, but computational analysis of the big data sets involved forms the bottleneck toward the creation of multiscale models of brain structure and function. While a full accounting of techniques and progress toward a comprehensive model of brain anatomy and function is beyond the scope of this or any other single paper, this review serves to highlight the opportunities for analysis of neuronal spine anatomy and function provided by new imaging technologies and the high-throughput application of older technologies while surveying the strengths and weaknesses of currently available computational analytical tools and room for future improvement.

  16. Mapping Molecular Function to Biological Nanostructure: Combining Structured Illumination Microscopy with Fluorescence Lifetime Imaging (SIM + FLIM

    Directory of Open Access Journals (Sweden)

    Frederik Görlitz

    2017-07-01

    Full Text Available We present a new microscope integrating super-resolved imaging using structured illumination microscopy (SIM with wide-field optically sectioned fluorescence lifetime imaging (FLIM to provide optical mapping of molecular function and its correlation with biological nanostructure below the conventional diffraction limit. We illustrate this SIM + FLIM capability to map FRET readouts applied to the aggregation of discoidin domain receptor 1 (DDR1 in Cos 7 cells following ligand stimulation and to the compaction of DNA during the cell cycle.

  17. RNA systems biology: uniting functional discoveries and structural tools to understand global roles of RNAs.

    Science.gov (United States)

    Strobel, Eric J; Watters, Kyle E; Loughrey, David; Lucks, Julius B

    2016-06-01

    RNAs assume sophisticated structures that are active in myriad cellular processes. In this review, we highlight newly identified ribozymes, riboswitches, and small RNAs, some of which control the function of cellular metabolic and gene expression networks. We then examine recent developments in genome-wide RNA structure probing technologies that are yielding new insights into the structural landscape of the transcriptome. Finally, we discuss how these RNA 'structomic' methods can address emerging questions in RNA systems biology, from the mechanisms behind long non-coding RNAs to new bases for human diseases. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. [The influences of anterior disc displacement on oral mandibular function and morphology and their biological mechanisms].

    Science.gov (United States)

    Xia, Wendi; Fu, Kiayuan

    2016-03-01

    Anterior disc displacement is a common subtype seen in temporomandibular disorders (TMD) patients. It may cause mandibular movement disorders, such as clicking of joint, intermittent closed lock, limitation of mouth opening, etc. These disorders may affect the life qualities of patients. Anterior disc displacement may also cause mandibular malformations, especially among adolescents, which may affect the growth of condyle, therefore may have a correlation with mandibular retrusion or mandibular deviation when grown up. This paper going to review the influences of anterior disc displacement on oral mandibular function and morphology and their biological mechanisms.

  19. Translating inter-individual genetic variation to biological function in complex phenotypes

    DEFF Research Database (Denmark)

    Yadav, Rachita

    populations. Next, the second portion of this chapter describes a personalised genome study of an ancient genome which was conducted by calculating the genetic risk scores to unravel phenotypes. Appendix section (Chapter 8) comprises of an integrative functional analysis study of the changing proteome...... and phosphor-proteome in chemotherapy resistant breast cancer cell lines with high TIMP-1 gene expression. In summary, this thesis work demonstrates applications of various omic variations at different levels of complexity and their integration using systems biology based methodologies to associate them...... to multifactorial phenotypes. These studies help in revealing pivotal mechanistic details concerning the phenotypes, which can be further utilized in drug designing and disease management....

  20. Insights into the biological functions of Dock family guanine nucleotide exchange factors.

    Science.gov (United States)

    Laurin, Mélanie; Côté, Jean-François

    2014-03-15

    Rho GTPases play key regulatory roles in many aspects of embryonic development, regulating processes such as differentiation, proliferation, morphogenesis, and migration. Two families of guanine nucleotide exchange factors (GEFs) found in metazoans, Dbl and Dock, are responsible for the spatiotemporal activation of Rac and Cdc42 proteins and their downstream signaling pathways. This review focuses on the emerging roles of the mammalian DOCK family in development and disease. We also discuss, when possible, how recent discoveries concerning the biological functions of these GEFs might be exploited for the development of novel therapeutic strategies.

  1. The Evolution of Human Basophil Biology from Neglect towards Understanding of Their Immune Functions.

    Science.gov (United States)

    Steiner, Markus; Huber, Sara; Harrer, Andrea; Himly, Martin

    2016-01-01

    Being discovered long ago basophils have been neglected for more than a century. During the past decade evidence emerged that basophils share features of innate and adaptive immunity. Nowadays, basophils are best known for their striking effector role in the allergic reaction. They hence have been used for establishing new diagnostic tests and therapeutic approaches and for characterizing natural and recombinant allergens as well as hypoallergens, which display lower or diminished IgE-binding activity. However, it was a long way from discovery in 1879 until identification of their function in hypersensitivity reactions, including adverse drug reactions. Starting with a historical background, this review highlights the modern view on basophil biology.

  2. Engineering Biological C-H Functionalization Leads to Allele-Specific Regulation of Histone Demethylases.

    Science.gov (United States)

    Breski, Megan; Dey, Debasis; Obringer, Sara; Sudhamalla, Babu; Islam, Kabirul

    2016-10-06

    Oxidative C-H hydroxylation of methyl groups, followed by their removal from DNA, RNA or histones, is an epigenetic process critical to transcriptional reprogramming and cell fate determination. This reaction is catalyzed by Fe(II)-dependent dioxygenases using the essential metabolite 2-ketoglutarate (2KG) as a cofactor. Given that the human genome encodes for more than 60 2KG-dependent dioxygenases, assigning their individual functions remains a significant challenge. Here we describe a protein-ligand interface engineering approach to break the biochemical degeneracy of these enzymes. Using histone lysine demethylase 4 (KDM4) as a proof-of-concept, we show that the enzyme active site can be expanded to employ bulky 2KG analogues that do not sensitize wild type demethylases. We establish the orthogonality, substrate specificity and catalytic competency of the engineered demethylation apparatus in biochemical assays. We further demonstrate demethylation of cognate substrates in physiologically relevant settings. Our results provide a para-digm for rapid and conditional manipulation of histone deme-thylases to uncloak their isoform-specific functions.

  3. Evaluation of the Expanded Disability Status Scale and the Multiple Sclerosis Functional Composite as clinical endpoints in multiple sclerosis clinical trials: quantitative meta-analyses.

    Science.gov (United States)

    Bin Sawad, Aseel; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Turkistani, Fatema

    2016-12-01

    This study compared the sensitivity of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) as clinical endpoints in multiple sclerosis (MS) clinical trials. Medline (1946 through 12 September 2014) and Embase (1974 through 12 September 2014) databases searches were conducted using keywords and Medical Subject Heading (MeSH) terms related to MS, EDSS, and MSFC. Only studies that used the EDSS and MSFC as endpoints were assessed. All statistical analyses were conducted using comprehensive meta-analysis (CMA). The percentages of the overall changes in EDSS and MSFC were compared. The relative risks were calculated in randomized clinical trials (RCTs). A total of 123 studies were identified. There were nine studies (6 case series and 3 RCTs) included in the analysis. In the case series, the EDSS change rate in MS patients was 33.5% (95% CI: 12.9-63.2%) and the MSFC change rate was 30.3% (95% CI: 9.2-65.2%). In RCTs, patients who take the drug would be 22.9 times as likely as patients who did not take the drug to experience a change in the EDSS scale (RR = 22.9, 95% CI = 0.996-1.517, p = 0.055). Patients who take the drug would be 48.9 times as likely as patients who did not take the drug to experience a change in the MSFC scale (RR = 48.9, 95% CI = CI = 0.916-2.419, p = 0.108). This study focused only on MS patient improvement (positive changes) on the EDSS and MSFC. More studies are needed to include patient deterioration (negative changes) on EDSS and MSFC. There is controversy about the sensitivity of the EDSS and MSFC in detecting the progression of MS disease. The EDSS and MSFC are effective tools to assess the clinical severity and progression of MS disease. MSFC is more sensitive than EDSS in detecting the progression of MS disease.

  4. Multiplexing and demultiplexing logic functions for computing signal processing tasks in synthetic biology.

    Science.gov (United States)

    Pasotti, Lorenzo; Quattrocelli, Mattia; Galli, Daniela; De Angelis, Maria Gabriella Cusella; Magni, Paolo

    2011-07-01

    Building biological devices to perform computational and signal processing tasks is one of the main research issues in synthetic biology. Herein, two modular biological systems that could mimic multiplexing and demultiplexing logic functions are proposed and discussed. These devices, called multiplexer (mux) and demultiplexer (demux), respectively, have a remarkable importance in electronic, telecommunication, and signal processing systems and, similarly, they could play a crucial role if implemented in a living organism, such as Escherichia coli. BioBrick standard parts were used to design mux and demux and to construct two genetic circuits that could carry out the desired tasks. A modular approach, mimicking basic logic gates (AND, OR, and NOT) with protein/autoinducer or protein/DNA interactions and interconnecting them to create the final circuits, was adopted. A mathematical model of the designed gene networks was been defined and simulations performed to validate the expected behavior of the systems. In addition, circuit subparts were tested in vivo and the results used to determine some of the parameters of the mathematical model. According to both the experimental and simulated results, guidelines for future finalization of mux and demux are provided. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Importance of N-Glycosylation on CD147 for Its Biological Functions

    Directory of Open Access Journals (Sweden)

    Yang Bai

    2014-04-01

    Full Text Available Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation.

  6. Enzymes for ecdysteroid biosynthesis: their biological functions in insects and beyond.

    Science.gov (United States)

    Niwa, Ryusuke; Niwa, Yuko S

    2014-01-01

    Steroid hormones are responsible for the coordinated regulation of many aspects of biological processes in multicellular organisms. Since the last century, many studies have identified and characterized steroidogenic enzymes in vertebrates, including mammals. However, much less is known about invertebrate steroidogenic enzymes. In the last 15 years, a number of steroidogenic enzymes and their functions have been characterized in ecdysozoan animals, especially in the fruit fly Drosophila melanogaster. In this review, we summarize the latest knowledge of enzymes crucial for synthesizing ecdysteroids, the principal insect steroid hormones. We also discuss the functional conservation and diversity of ecdysteroidogenic enzymes in other insects and even non-insect species, such as nematodes, vertebrates, and lower eukaryotes.

  7. Merger of Ayurveda and Tissue Culture-Based Functional Genomics: Inspirations from Systems Biology

    Directory of Open Access Journals (Sweden)

    Wadhwa Renu

    2008-03-01

    Full Text Available Abstract Ayurveda is one of the ancient systems of health care of Indian origin. Roughly translated into "Knowledge of life", it is based on the use of natural herbs and herb products for therapeutic measures to boost physical, mental, social and spiritual harmony and improve quality of life. Although sheltered with long history and high trust, ayurveda principles have not entered laboratories and only a handful of studies have identified pure components and molecular pathways for its life-enhancing effects. In the post-genomic era, genome-wide functional screenings for targets for diseases is the most recent and practical approach. We illustrate here the merger of ayurveda and functional genomics in a systems biology scenario that reveals the pathway analysis of crude and active components and inspire ayurveda practice for health benefits, disease prevention and therapeutics.

  8. The RNAi Universe in Fungi: A Varied Landscape of Small RNAs and Biological Functions.

    Science.gov (United States)

    Torres-Martínez, Santiago; Ruiz-Vázquez, Rosa M

    2017-09-08

    RNA interference (RNAi) is a conserved eukaryotic mechanism that uses small RNA molecules to suppress gene expression through sequence-specific messenger RNA degradation, translational repression, or transcriptional inhibition. In filamentous fungi, the protective function of RNAi in the maintenance of genome integrity is well known. However, knowledge of the regulatory role of RNAi in fungi has had to wait until the recent identification of different endogenous small RNA classes, which are generated by distinct RNAi pathways. In addition, RNAi research on new fungal models has uncovered the role of small RNAs and RNAi pathways in the regulation of diverse biological functions. In this review, we give an up-to-date overview of the different classes of small RNAs and RNAi pathways in fungi and their roles in the defense of genome integrity and regulation of fungal physiology and development, as well as in the interaction of fungi with biotic and abiotic environments.

  9. Autism, Asperger's syndrome and the Crick-Mitchison theory of the biological function of REM sleep.

    Science.gov (United States)

    Brown, D W

    1996-11-01

    Autism, Asperger's syndrome and other autistic syndromes are developmental brain disorders that cause serious impairments in communication, social interaction, empathy, mood and play. In addition to such deficits, the autistic syndromes involve pathologically high levels of repetitive, stereotypic, ritualistic, compulsive or obsessive behavior, together with extreme resistance to change. According to the Crick-Mitchison theory of the biological function of rapid eye movement sleep, normal brain development in the fetus and infant depends on undisrupted function of a 'reverse learning' mechanism during rapid eye movement sleep. Could abnormalities in this hypothetical reverse learning during rapid eye movement sleep in the fetus explain some aspects of the autistic syndromes? Does the Crick-Mitchison theory suggest if a drug could interfere with rapid eye movement sleep and cross the placental barrier, then that drug might cause developmental brain disorders in the fetus? Should all pregnant women completely avoid caffeine or any agent that might disrupt serotonergic or cholinergic systems?

  10. Differential Function of Lip Residues in the Mechanism and Biology of an Anthrax Hemophore

    Energy Technology Data Exchange (ETDEWEB)

    Ekworomadu, MarCia T.; Poor, Catherine B.; Owens, Cedric P.; Balderas, Miriam A.; Fabian, Marian; Olson, John S.; Murphy, Frank; Balkabasi, Erol; Honsa, Erin S.; He, Chuan; Goulding, Celia W.; Maresso, Anthony W. (Baylor); (UCI); (Cornell); (Rice); (UC)

    2014-10-02

    To replicate in mammalian hosts, bacterial pathogens must acquire iron. The majority of iron is coordinated to the protoporphyrin ring of heme, which is further bound to hemoglobin. Pathogenic bacteria utilize secreted hemophores to acquire heme from heme sources such as hemoglobin. Bacillus anthracis, the causative agent of anthrax disease, secretes two hemophores, IsdX1 and IsdX2, to acquire heme from host hemoglobin and enhance bacterial replication in iron-starved environments. Both proteins contain NEAr-iron Transporter (NEAT) domains, a conserved protein module that functions in heme acquisition in Gram-positive pathogens. Here, we report the structure of IsdX1, the first of a Gram-positive hemophore, with and without bound heme. Overall, IsdX1 forms an immunoglobin-like fold that contains, similar to other NEAT proteins, a 3{sub 10}-helix near the heme-binding site. Because the mechanistic function of this helix in NEAT proteins is not yet defined, we focused on the contribution of this region to hemophore and NEAT protein activity, both biochemically and biologically in cultured cells. Site-directed mutagenesis of amino acids in and adjacent to the helix identified residues important for heme and hemoglobin association, with some mutations affecting both properties and other mutations affecting only heme stabilization. IsdX1 with mutations that reduced the ability to associate with hemoglobin and bind heme failed to restore the growth of a hemophore-deficient strain of B. anthracis on hemoglobin as the sole iron source. These data indicate that not only is the 3{sub 10}-helix important for NEAT protein biology, but also that the processes of hemoglobin and heme binding can be both separate as well as coupled, the latter function being necessary for maximal heme-scavenging activity. These studies enhance our understanding of NEAT domain and hemophore function and set the stage for structure-based inhibitor design to block NEAT domain interaction with

  11. Wnt signaling in regulation of biological functions of the nurse cell harboring Trichinella spp.

    Science.gov (United States)

    Dabrowska, Magdalena; Skoneczny, Marek; Zielinski, Zbigniew; Rode, Wojciech

    2016-09-02

    The nurse cell (NC) constitutes in mammalian skeletal muscles a confined intracellular niche to support the metabolic needs of muscle larvae of Trichinella spp. encapsulating species. The main biological functions of NC were identified as hypermitogenic growth arrest and pro-inflammatory phenotype, both inferred to depend on AP-1 (activator protein 1) transcription factor. Since those functions, as well as AP-1 activity, are known to be regulated among other pathways, also by Wnt (Wingless-Type of Mouse Mammary Tumor Virus Integration Site) signaling, transcription profiling of molecules participating in Wnt signaling cascades in NC, was performed. Wnt signaling-involved gene expression level was measured by quantitative RT-PCR approach with the use of Qiagen RT(2) Profiler PCR Arrays and complemented by that obtained by searching microarray data sets characterizing NC transcriptome. The genes involved in inhibition of canonical Wnt/β-catenin signaling cascade as well as leading to β-catenin degradation were found expressed in NC at high level, indicating inhibition of this cascade activity. High expression in NC of genes transmitting the signal of Wnt non-canonical signaling cascades leading to activation of AP-1 transcription factor, points to predominant role of non-canonical Wnt signaling in a long term maintenance of NC biological functions. Canonical Wnt/β-catenin signaling cascade is postulated to play a role at the early stages of NC formation when muscle regeneration process is triggered. Following mis-differentiation of infected myofiber and setting of NC functional specificity, are inferred to be controlled among other pathways, by Wnt non-canonical signaling cascades.

  12. Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review.

    Science.gov (United States)

    Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R

    2015-07-06

    The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.

  13. Determining the impacts of trawling on benthic function in European waters : a biological traits approach

    DEFF Research Database (Denmark)

    Bolam, Stefan; Kenny, Andrew; Garcia, Clement

    One of the most widespread yet manageable pressures we impose on the seabed is disturbance of the substrate by towed demersal fishing gear (bottom trawling and dredging). Over the past forty to fifty years, many studies have been conducted specifically aiming to understand the impacts of such fis......One of the most widespread yet manageable pressures we impose on the seabed is disturbance of the substrate by towed demersal fishing gear (bottom trawling and dredging). Over the past forty to fifty years, many studies have been conducted specifically aiming to understand the impacts...... the functional impacts of this activity (as opposed to impacts on the structure of benthic assemblages) has only recently been attempted. Advances in the application of biological traits analysis (BTA) wherein the assemblages are described in terms of their life history, behavioural and morphological...... on benthic ecosystem functioning over much larger spatial scales than previously undertaken. Biological traits information from 887 stations across European waters (Norwegian, UK, Belgian, Dutch, Danish waters, the Mediterranean and Black Sea) were analysed to: i) quantify the relationships between infaunal...

  14. What will result from the interaction between functional and evolutionary biology?

    Science.gov (United States)

    Morange, Michel

    2011-03-01

    The modern synthesis has been considered to be wrongly called a "synthesis", since it had completely excluded embryology, and many other disciplines. The recent developments of Evo-Devo have been seen as a step in the right direction, as complementing the modern synthesis, and probably leading to a "new synthesis". My argument is that the absence of embryology from the modern synthesis was the visible sign of a more profound lack: the absence of functional biology in the evolutionary synthesis. I will consider the reasons for this absence, as well as the recent transformations which favoured a closer interaction between these two branches of biology. Then I will describe two examples of recent work in which functional and evolutionary questioning were tightly linked. The most significant part of the paper will be devoted to the transformation of evolutionary theory that can be expected from this encounter: a deep transformation, or simply an experimental confirmation of this theory? I will not choose between these two different possibilities, but will discuss some of the difficulties which make the choice problematic. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Thyroid Autoimmunity and Function after Treatment with Biological Antirheumatic Agents in Rheumatoid Arthritis.

    Science.gov (United States)

    Bliddal, Sofie; Borresen, Stina Willemoes; Feldt-Rasmussen, Ulla

    2017-01-01

    With the increased pro-inflammatory response in both rheumatoid arthritis and thyroid autoimmune diseases, treatment with biological antirheumatic agents (BAAs) of the former may affect the course of the latter. In hepatitis C and cancer patients, treatment with biological agents substantially increases the risk of developing thyroid autoimmunity. As the use of BAAs in the treatment of rheumatoid arthritis is increasing, this review aimed to investigate if such use affected thyroid status in rheumatoid arthritis patients. We conducted a systematic literature search and included six studies with a total of 311 patients as well as three case reports. The patients were treated with tumor necrosis factor-α inhibitors (infliximab, etanercept, or adalimumab) or the monoclonal CD20-antibody rituximab. There was a non-significant trend of slight improvement of both thyroid function and autoantibody status: a reduction of thyroid peroxidase and thyroglobulin antibody concentrations, and a reduction of thyrotropin levels in hypothyroid patients. Despite the small number of studies, they presented compliant data. The BAAs used in rheumatoid arthritis thus did not seem to negatively affect thyroid status in patients with rheumatoid arthritis and can be considered safe with regard to thyroid autoimmunity. However, the well-established association between rheumatic diseases and thyroid autoimmunity necessitates continued monitoring of thyroid function in patients with rheumatoid arthritis. Each new BAA should be scrutinized for its effect on thyroid as well as other autoimmune diseases in order to establish concise recommendations for patient follow-up for each agent and each disease.

  16. Role of soil biology and soil functions in relation to land use intensity.

    Science.gov (United States)

    Bondi, Giulia; Wall, David; Bacher, Matthias; Emmet-Booth, Jeremy; Graça, Jessica; Marongiu, Irene; Creamer, Rachel

    2017-04-01

    The delivery of the ecosystem's functions is predominantly controlled by soil biology. The biology found in a gram of soil contains more than ten thousand individual species of bacteria and fungi (Torsvik et al., 1990). Understanding the role and the requirements of these organisms is essential for the protection and the sustainable use of soils. Soil biology represents the engine of all the processes occurring in the soil and it supports the ecosystem services such as: 1) nutrient mineralisation 2) plant production 3) water purification and regulation and 4) carbon cycling and storage. During the last years land management type and intensity have been identified as major drivers for microbial performance in soil. For this reason land management needs to be appropriately studied to understand the role of soil biology within this complex interplay of functions. We aimed to study whether and how land management drives soil biological processes and related functions. To reach this objective we built a land use intensity index (LUI) able to quantify the impact of the common farming practices carried out in Irish grassland soils. The LUI is derived from a detailed farmer questionnaire on grassland management practices at 38 farms distributed in the five major agro-climatic regions of Ireland defined by Holden and Brereton (2004). Soils were classified based on their drainage status according to the Irish Soil Information System by Creamer et al. (2014). This detailed questionnaire is then summarised into 3 management intensity components: (i) intensity of Fertilisation (Fi), (ii) frequency of Mowing (Mi) and (iii) intensity of Livestock Grazing (Gi). Sites were sampled to assess the impact of land management intensity on microbial community structure and enzyme behaviour in relation to nitrogen, phosphorus and carbon cycling. Preliminary results for enzymes linked to C and N cycles showed higher activity in relation to low grazing pressure (low Gi). Enzymes linked to P

  17. How biological soil crusts became recognized as a functional unit: a selective history

    Science.gov (United States)

    Lange, Otto L.; Belnap, Jayne

    2016-01-01

    It is surprising that despite the world-wide distribution and general importance of biological soil crusts (biocrusts), scientific recognition and functional analysis of these communities is a relatively young field of science. In this chapter, we sketch the historical lines that led to the recognition of biocrusts as a community with important ecosystem functions. The idea of biocrusts as a functional ecological community has come from two main scientific branches: botany and soil science. For centuries, botanists have long recognized that multiple organisms colonize the soil surface in the open and often dry areas occurring between vascular plants. Much later, after the initial taxonomic and phyto-sociological descriptions were made, soil scientists and agronomists observed that these surface organisms interacted with soils in ways that changed the soil structure. In the 1970’s, research on these communities as ecological units that played an important functional role in drylands began in earnest, and these studies have continued to this day. Here, we trace the history of these studies from the distant past until 1990, when biocrusts became well-known to scientists and the public.

  18. Covalent functionalization of zinc oxide nanowires for high sensitivity p-nitrophenol detection in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Anurag, E-mail: agupta16@crimson.ua.edu [The University of Alabama, 101 Houser Hall, Tuscaloosa, AL 35487 (United States); Kim, Bruce C. [The University of Alabama, 101 Houser Hall, Tuscaloosa, AL 35487 (United States); Edwards, Eugene; Brantley, Christina; Ruffin, Paul [U.S. Army, RDECOM/AMRDEC, 5400 Fowler Road, Redstone Arsenal, AL 35898 (United States)

    2012-11-01

    Highlights: Black-Right-Pointing-Pointer High quality synthesis of ZnO nanowires through a CVD process and characterization. Black-Right-Pointing-Pointer Covalent functionalization with fluorescent receptor to produce novel hybrid organic-inorganic system. Black-Right-Pointing-Pointer Surface sensitive XPS results are analyzed to deduce proof of covalent functionalization. Black-Right-Pointing-Pointer Detection limit of 28 ppb estimated for sensor through fluorescence studies. Black-Right-Pointing-Pointer Highly sensitive and selective sensing platform design is proposed based on empirical findings. - Abstract: High-quality zinc oxide (ZnO) nanowires were synthesized using the atmospheric chemical vapor deposition technique and were appropriately characterized. Subsequently, the nanowire surface was covalently grafted with 1-pyrenebutyric acid (PBA) fluorophore, and surface-sensitive X-ray photoelectron spectroscopy and Fourier transform infrared-attenuated total reflectance spectroscopy were utilized to confirm the functionalization of 1-pyrenebutyric acid on the nanowire surface. Additionally, photoluminescence (PL) measurements were used to evaluate the optical behavior of pristine nanowires. Through fluorescence quenching of 1-pyrenebutyric acid by p-nitrophenol, a detection limit of 28 ppb was estimated. Based on these findings, ZnO nanowires functionalized with 1-pyrenebutyric acid are envisaged as extremely sensitive platforms for the ultra-trace detection of p-nitrophenol in biological systems.

  19. Unsupervised Learning and Pattern Recognition of Biological Data Structures with Density Functional Theory and Machine Learning.

    Science.gov (United States)

    Chen, Chien-Chang; Juan, Hung-Hui; Tsai, Meng-Yuan; Lu, Henry Horng-Shing

    2018-01-11

    By introducing the methods of machine learning into the density functional theory, we made a detour for the construction of the most probable density function, which can be estimated by learning relevant features from the system of interest. Using the properties of universal functional, the vital core of density functional theory, the most probable cluster numbers and the corresponding cluster boundaries in a studying system can be simultaneously and automatically determined and the plausibility is erected on the Hohenberg-Kohn theorems. For the method validation and pragmatic applications, interdisciplinary problems from physical to biological systems were enumerated. The amalgamation of uncharged atomic clusters validated the unsupervised searching process of the cluster numbers and the corresponding cluster boundaries were exhibited likewise. High accurate clustering results of the Fisher's iris dataset showed the feasibility and the flexibility of the proposed scheme. Brain tumor detections from low-dimensional magnetic resonance imaging datasets and segmentations of high-dimensional neural network imageries in the Brainbow system were also used to inspect the method practicality. The experimental results exhibit the successful connection between the physical theory and the machine learning methods and will benefit the clinical diagnoses.

  20. Layouts of Expander Graphs

    OpenAIRE

    Dujmović, Vida; Sidiropoulos, Anastasios; Wood, David R.

    2015-01-01

    Bourgain and Yehudayoff recently constructed $O(1)$-monotone bipartite expanders. By combining this result with a generalisation of the unraveling method of Kannan, we construct 3-monotone bipartite expanders, which is best possible. We then show that the same graphs admit 3-page book embeddings, 2-queue layouts, 4-track layouts, and have simple thickness 2. All these results are best possible.

  1. Multiscale modeling of biological functions: from enzymes to molecular machines (Nobel Lecture).

    Science.gov (United States)

    Warshel, Arieh

    2014-09-15

    A detailed understanding of the action of biological molecules is a pre-requisite for rational advances in health sciences and related fields. Here, the challenge is to move from available structural information to a clear understanding of the underlying function of the system. In light of the complexity of macromolecular complexes, it is essential to use computer simulations to describe how the molecular forces are related to a given function. However, using a full and reliable quantum mechanical representation of large molecular systems has been practically impossible. The solution to this (and related) problems has emerged from the realization that large systems can be spatially divided into a region where the quantum mechanical description is essential (e.g. a region where bonds are being broken), with the remainder of the system being represented on a simpler level by empirical force fields. This idea has been particularly effective in the development of the combined quantum mechanics/molecular mechanics (QM/MM) models. Here, the coupling between the electrostatic effects of the quantum and classical subsystems has been a key to the advances in describing the functions of enzymes and other biological molecules. The same idea of representing complex systems in different resolutions in both time and length scales has been found to be very useful in modeling the action of complex systems. In such cases, starting with coarse grained (CG) representations that were originally found to be very useful in simulating protein folding, and augmenting them with a focus on electrostatic energies, has led to models that are particularly effective in probing the action of molecular machines. The same multiscale idea is likely to play a major role in modeling of even more complex systems, including cells and collections of cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Induced Pluripotent Stem Cell–Derived Cardiomyocytes Provide In Vivo Biological Pacemaker Function

    Science.gov (United States)

    Chauveau, Samuel; Anyukhovsky, Evgeny P.; Ben-Ari, Meital; Naor, Shulamit; Jiang, Ya-Ping; Danilo, Peter; Rahim, Tania; Burke, Stephanie; Qiu, Xiaoliang; Potapova, Irina A.; Doronin, Sergey V.; Brink, Peter R.; Binah, Ofer

    2017-01-01

    Background— Although multiple approaches have been used to create biological pacemakers in animal models, induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) have not been investigated for this purpose. We now report pacemaker function of iPSC-CMs in a canine model. Methods and Results— Embryoid bodies were derived from human keratinocytes, their action potential characteristics determined, and their gene expression profiles and markers of differentiation identified. Atrioventricular blocked dogs were immunosuppressed, instrumented with VVI pacemakers, and injected subepicardially into the anterobasal left ventricle with 40 to 75 rhythmically contracting embryoid bodies (totaling 1.3–2×106 cells). ECG and 24-hour Holter monitoring were performed biweekly. After 4 to 13 weeks, epinephrine (1 μg kg−1 min−1) was infused, and the heart removed for histological or electrophysiological study. iPSC-CMs largely lost the markers of pluripotency, became positive for cardiac-specific markers. and manifested If-dependent automaticity. Epicardial pacing of the injection site identified matching beats arising from that site by week 1 after implantation. By week 4, 20% of beats were electronically paced, 60% to 80% of beats were matching, and mean and maximal biological pacemaker rates were 45 and 75 beats per minute. Maximum night and day rates of matching beats were 53±6.9 and 69±10.4 beats per minute, respectively, at 4 weeks. Epinephrine increased rate of matching beats from 35±4.3 to 65±4.0 beats per minute. Incubation of embryoid bodies with the vital dye, Dil, revealed the persistence of injected cells at the site of administration. Conclusions— iPSC-CMs can integrate into host myocardium and create a biological pacemaker. Although this is a promising development, rate and rhythm of the iPSC-CMs pacemakers remain to be optimized. PMID:28500172

  3. Mammalian Synthetic Biology: Engineering Biological Systems.

    Science.gov (United States)

    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.

  4. Exploring New Biological Functions of Amyloids: Bacteria Cell Agglutination Mediated by Host Protein Aggregation

    Science.gov (United States)

    Torrent, Marc; Pulido, David; Nogués, M. Victòria; Boix, Ester

    2012-01-01

    Antimicrobial proteins and peptides (AMPs) are important effectors of the innate immune system that play a vital role in the prevention of infections. Recent advances have highlighted the similarity between AMPs and amyloid proteins. Using the Eosinophil Cationic Protein as a model, we have rationalized the structure-activity relationships between amyloid aggregation and antimicrobial activity. Our results show how protein aggregation can induce bacteria agglutination and cell death. Using confocal and total internal reflection fluorescence microscopy we have tracked the formation in situ of protein amyloid-like aggregates at the bacteria surface and on membrane models. In both cases, fibrillar aggregates able to bind to amyloid diagnostic dyes were detected. Additionally, a single point mutation (Ile13 to Ala) can suppress the protein amyloid behavior, abolishing the agglutinating activity and impairing the antimicrobial action. The mutant is also defective in triggering both leakage and lipid vesicle aggregation. We conclude that ECP aggregation at the bacterial surface is essential for its cytotoxicity. Hence, we propose here a new prospective biological function for amyloid-like aggregates with potential biological relevance. PMID:23133388

  5. Correlation of Fragile Histidine Triad (Fhit) Protein Structural Features with Effector Interactions and Biological Functions*

    Science.gov (United States)

    Pichiorri, Flavia; Okumura, Hiroshi; Nakamura, Tatsuya; Garrison, Preston N.; Gasparini, Pierluigi; Suh, Sung-Suk; Druck, Teresa; McCorkell, Kelly A.; Barnes, Larry D.; Croce, Carlo M.; Huebner, Kay

    2009-01-01

    We have previously shown that Fhit tumor suppressor protein interacts with Hsp60 chaperone machinery and ferredoxin reductase (Fdxr) protein. Fhit-effector interactions are associated with a Fhit-dependent increase in Fdxr stability, followed by generation of reactive oxygen species and apoptosis induction under conditions of oxidative stress. To define Fhit structural features that affect interactions, downstream signaling, and biological outcomes, we used cancer cells expressing Fhit mutants with amino acid substitutions that alter enzymatic activity, enzyme substrate binding, or phosphorylation at tyrosine 114. Gastric cancer cell clones stably expressing mutants that do not bind substrate or cannot be phosphorylated showed decreased binding to Hsp60 and Fdxr and reduced mitochondrial localization. Expression of Fhit or mutants that bind interactor proteins results in oxidative damage and accumulation of cells in G2/M or sub-G1 fractions after peroxide treatment; noninteracting mutants are defective in these biological effects. Gastric cancer clones expressing noncomplexing Fhit mutants show reduction of Fhit tumor suppressor activity, confirming that substrate binding, interaction with heat shock proteins, mitochondrial localization, and interaction with Fdxr are important for Fhit tumor suppressor function. PMID:19004824

  6. Correlation of fragile histidine triad (Fhit) protein structural features with effector interactions and biological functions.

    Science.gov (United States)

    Pichiorri, Flavia; Okumura, Hiroshi; Nakamura, Tatsuya; Garrison, Preston N; Gasparini, Pierluigi; Suh, Sung-Suk; Druck, Teresa; McCorkell, Kelly A; Barnes, Larry D; Croce, Carlo M; Huebner, Kay

    2009-01-09

    We have previously shown that Fhit tumor suppressor protein interacts with Hsp60 chaperone machinery and ferredoxin reductase (Fdxr) protein. Fhit-effector interactions are associated with a Fhit-dependent increase in Fdxr stability, followed by generation of reactive oxygen species and apoptosis induction under conditions of oxidative stress. To define Fhit structural features that affect interactions, downstream signaling, and biological outcomes, we used cancer cells expressing Fhit mutants with amino acid substitutions that alter enzymatic activity, enzyme substrate binding, or phosphorylation at tyrosine 114. Gastric cancer cell clones stably expressing mutants that do not bind substrate or cannot be phosphorylated showed decreased binding to Hsp60 and Fdxr and reduced mitochondrial localization. Expression of Fhit or mutants that bind interactor proteins results in oxidative damage and accumulation of cells in G(2)/M or sub-G(1) fractions after peroxide treatment; noninteracting mutants are defective in these biological effects. Gastric cancer clones expressing noncomplexing Fhit mutants show reduction of Fhit tumor suppressor activity, confirming that substrate binding, interaction with heat shock proteins, mitochondrial localization, and interaction with Fdxr are important for Fhit tumor suppressor function.

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

    Science.gov (United States)

    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.

  8. The role of ontologies in biological and biomedical research: a functional perspective

    KAUST Repository

    Hoehndorf, Robert

    2015-04-10

    Ontologies are widely used in biological and biomedical research. Their success lies in their combination of four main features present in almost all ontologies: provision of standard identifiers for classes and relations that represent the phenomena within a domain; provision of a vocabulary for a domain; provision of metadata that describes the intended meaning of the classes and relations in ontologies; and the provision of machine-readable axioms and definitions that enable computational access to some aspects of the meaning of classes and relations. While each of these features enables applications that facilitate data integration, data access and analysis, a great potential lies in the possibility of combining these four features to support integrative analysis and interpretation of multimodal data. Here, we provide a functional perspective on ontologies in biology and biomedicine, focusing on what ontologies can do and describing how they can be used in support of integrative research. We also outline perspectives for using ontologies in data-driven science, in particular their application in structured data mining and machine learning applications.

  9. Green leaf volatiles: biosynthesis, biological functions and their applications in biotechnology.

    Science.gov (United States)

    ul Hassan, Muhammad Naeem; Zainal, Zamri; Ismail, Ismanizan

    2015-08-01

    Plants have evolved numerous constitutive and inducible defence mechanisms to cope with biotic and abiotic stresses. These stresses induce the expression of various genes to activate defence-related pathways that result in the release of defence chemicals. One of these defence mechanisms is the oxylipin pathway, which produces jasmonates, divinylethers and green leaf volatiles (GLVs) through the peroxidation of polyunsaturated fatty acids (PUFAs). GLVs have recently emerged as key players in plant defence, plant-plant interactions and plant-insect interactions. Some GLVs inhibit the growth and propagation of plant pathogens, including bacteria, viruses and fungi. In certain cases, GLVs released from plants under herbivore attack can serve as aerial messengers to neighbouring plants and to attract parasitic or parasitoid enemies of the herbivores. The plants that perceive these volatile signals are primed and can then adapt in preparation for the upcoming challenges. Due to their 'green note' odour, GLVs impart aromas and flavours to many natural foods, such as vegetables and fruits, and therefore, they can be exploited in industrial biotechnology. The aim of this study was to review the progress and recent developments in research on the oxylipin pathway, with a specific focus on the biosynthesis and biological functions of GLVs and their applications in industrial biotechnology. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  10. Exploring new biological functions of amyloids: bacteria cell agglutination mediated by host protein aggregation.

    Directory of Open Access Journals (Sweden)

    Marc Torrent

    Full Text Available Antimicrobial proteins and peptides (AMPs are important effectors of the innate immune system that play a vital role in the prevention of infections. Recent advances have highlighted the similarity between AMPs and amyloid proteins. Using the Eosinophil Cationic Protein as a model, we have rationalized the structure-activity relationships between amyloid aggregation and antimicrobial activity. Our results show how protein aggregation can induce bacteria agglutination and cell death. Using confocal and total internal reflection fluorescence microscopy we have tracked the formation in situ of protein amyloid-like aggregates at the bacteria surface and on membrane models. In both cases, fibrillar aggregates able to bind to amyloid diagnostic dyes were detected. Additionally, a single point mutation (Ile13 to Ala can suppress the protein amyloid behavior, abolishing the agglutinating activity and impairing the antimicrobial action. The mutant is also defective in triggering both leakage and lipid vesicle aggregation. We conclude that ECP aggregation at the bacterial surface is essential for its cytotoxicity. Hence, we propose here a new prospective biological function for amyloid-like aggregates with potential biological relevance.

  11. FUSE: a profit maximization approach for functional summarization of biological networks

    Directory of Open Access Journals (Sweden)

    Seah Boon-Siew

    2012-03-01

    Full Text Available Abstract Background The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein interaction network (PPI using graph theoretic analysis. Despite the recent progress, systems level analysis of PPIS remains a daunting task as it is challenging to make sense out of the deluge of high-dimensional interaction data. Specifically, techniques that automatically abstract and summarize PPIS at multiple resolutions to provide high level views of its functional landscape are still lacking. We present a novel data-driven and generic algorithm called FUSE (Functional Summary Generator that generates functional maps of a PPI at different levels of organization, from broad process-process level interactions to in-depth complex-complex level interactions, through a pro t maximization approach that exploits Minimum Description Length (MDL principle to maximize information gain of the summary graph while satisfying the level of detail constraint. Results We evaluate the performance of FUSE on several real-world PPIS. We also compare FUSE to state-of-the-art graph clustering methods with GO term enrichment by constructing the biological process landscape of the PPIS. Using AD network as our case study, we further demonstrate the ability of FUSE to quickly summarize the network and identify many different processes and complexes that regulate it. Finally, we study the higher-order connectivity of the human PPI. Conclusion By simultaneously evaluating interaction and annotation data, FUSE abstracts higher-order interaction maps by reducing the details of the underlying PPI to form a functional summary graph of interconnected functional clusters. Our results demonstrate its effectiveness and superiority over state-of-the-art graph clustering methods with GO term enrichment.

  12. FUSE: a profit maximization approach for functional summarization of biological networks.

    Science.gov (United States)

    Seah, Boon-Siew; Bhowmick, Sourav S; Dewey, C Forbes; Yu, Hanry

    2012-03-21

    The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein interaction network (PPI) using graph theoretic analysis. Despite the recent progress, systems level analysis of PPIS remains a daunting task as it is challenging to make sense out of the deluge of high-dimensional interaction data. Specifically, techniques that automatically abstract and summarize PPIS at multiple resolutions to provide high level views of its functional landscape are still lacking. We present a novel data-driven and generic algorithm called FUSE (Functional Summary Generator) that generates functional maps of a PPI at different levels of organization, from broad process-process level interactions to in-depth complex-complex level interactions, through a pro t maximization approach that exploits Minimum Description Length (MDL) principle to maximize information gain of the summary graph while satisfying the level of detail constraint. We evaluate the performance of FUSE on several real-world PPIS. We also compare FUSE to state-of-the-art graph clustering methods with GO term enrichment by constructing the biological process landscape of the PPIS. Using AD network as our case study, we further demonstrate the ability of FUSE to quickly summarize the network and identify many different processes and complexes that regulate it. Finally, we study the higher-order connectivity of the human PPI. By simultaneously evaluating interaction and annotation data, FUSE abstracts higher-order interaction maps by reducing the details of the underlying PPI to form a functional summary graph of interconnected functional clusters. Our results demonstrate its effectiveness and superiority over state-of-the-art graph clustering methods with GO term enrichment.

  13. Clinical Characteristics of Rheumatoid Arthritis Patients Achieving Functional Remission with Six Months of Biological DMARDs Treatment.

    Science.gov (United States)

    Miwa, Yusuke; Takahashi, Ryo; Ikari, Yuzo; Maeoka, Airi; Nishimi, Shinichiro; Oguro, Nao; Hayashi, Tomoki; Hatano, Mika; Isojima, Sakiko; Yanai, Ryo; Kasama, Tsuyoshi; Toyoshima, Yoichi; Inagaki, Katsunori; Sanada, Kenji

    2017-01-01

    Objective Although previous studies have reported the prognostic factors for functional remission, no reports have cited the predictive factors. Our aim was to study the predictive factors for functional remission, which is a treatment goal in rheumatoid arthritis (RA), after receiving biological disease-modifying antirheumatic drugs (bDMARDs) treatment for six months. Methods The study consisted of 333 RA patients treated with bDMARDs for six months. The following patient characteristics were investigated: age, gender, disease duration, type of bDMARDs, baseline steroid and methotrexate dosage, and levels of serum rheumatoid factor, matrix metalloprotease, anti-cyclic citrullinated peptides antibody, tumor necrosis factor-α, and interleukin-6. In our evaluation, we used the Simplified Disease Activity Index (SDAI) for RA disease activity, health assessment questionnaire disability index (HAQ-DI) for activity of daily living, Short Form (SF)-36 for quality of life, and Hamilton Depression Rating Scale (HAM-D) or Self-rating Depression Scale (SDS) to determine the patients' depression status. The subjects were divided into two groups: patients with HAQ-DI≤0.5 and HAQ-DI>0.5 at 6 months. Results A univariate analysis comparing a group of RA patients without functional remission (n=68) showed that the patients with functional remission (n=164) had the following in common compared with those without remission: younger age, shorter disease duration, lower baseline steroid dosage, lower SDAI, lower HAQ-DI, higher SF-36, and lower HAM-D. Only lower HAQ-DI scores and "mental health" score on the SF-36 were detected using a logistic regression analysis. Conclusion These findings suggested that RA patients with lower HAQ-DI and lower depression scores at baseline were more likely to achieve functional remission using bDMARDs treatment than those without these variables.

  14. Biological conservation law as an emerging functionality in dynamical neuronal networks.

    Science.gov (United States)

    Podobnik, Boris; Jusup, Marko; Tiganj, Zoran; Wang, Wen-Xu; Buldú, Javier M; Stanley, H Eugene

    2017-11-07

    Scientists strive to understand how functionalities, such as conservation laws, emerge in complex systems. Living complex systems in particular create high-ordered functionalities by pairing up low-ordered complementary processes, e.g., one process to build and the other to correct. We propose a network mechanism that demonstrates how collective statistical laws can emerge at a macro (i.e., whole-network) level even when they do not exist at a unit (i.e., network-node) level. Drawing inspiration from neuroscience, we model a highly stylized dynamical neuronal network in which neurons fire either randomly or in response to the firing of neighboring neurons. A synapse connecting two neighboring neurons strengthens when both of these neurons are excited and weakens otherwise. We demonstrate that during this interplay between the synaptic and neuronal dynamics, when the network is near a critical point, both recurrent spontaneous and stimulated phase transitions enable the phase-dependent processes to replace each other and spontaneously generate a statistical conservation law-the conservation of synaptic strength. This conservation law is an emerging functionality selected by evolution and is thus a form of biological self-organized criticality in which the key dynamical modes are collective.

  15. Prediction of biological functions on glycosylation site migrations in human influenza H1N1 viruses.

    Science.gov (United States)

    Sun, Shisheng; Wang, Qinzhe; Zhao, Fei; Chen, Wentian; Li, Zheng

    2012-01-01

    Protein glycosylation alteration is typically employed by various viruses for escaping immune pressures from their hosts. Our previous work had shown that not only the increase of glycosylation sites (glycosites) numbers, but also glycosite migration might be involved in the evolution of human seasonal influenza H1N1 viruses. More importantly, glycosite migration was likely a more effectively alteration way for the host adaption of human influenza H1N1 viruses. In this study, we provided more bioinformatics and statistic evidences for further predicting the significant biological functions of glycosite migration in the host adaptation of human influenza H1N1 viruses, by employing homology modeling and in silico protein glycosylation of representative HA and NA proteins as well as amino acid variability analysis at antigenic sites of HA and NA. The results showed that glycosite migrations in human influenza viruses have at least five possible functions: to more effectively mask the antigenic sites, to more effectively protect the enzymatic cleavage sites of neuraminidase (NA), to stabilize the polymeric structures, to regulate the receptor binding and catalytic activities and to balance the binding activity of hemagglutinin (HA) with the release activity of NA. The information here can provide some constructive suggestions for the function research related to protein glycosylation of influenza viruses, although these predictions still need to be supported by experimental data.

  16. Restoration of voice function by using biological feedback in laryngeal and hypopharyngeal carcinoma patients

    Science.gov (United States)

    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.

  17. The biological function of pigeon crop milk and the regulation of its production.

    Science.gov (United States)

    Luo, Yi; Wang, Xun; Ma, Yao; Li, Xiao Kai

    2017-12-20

    The pigeon (Columba livia) is one of the few birds capable of secreting nutrients to nourish squabs. During the incubation period, the crop of the parent pigeon will be thickened. When squabs are hatched, the crop milk will be secreted from the crop and fed to squabs. The nutritional benefits are similar between the pigeon crop milk and mammalian milk, and both of them are regulated by prolactin. Prolactin stimulates the proliferation of crop epithelial cells, which eventually slough to form the crop milk. Evidence suggests that the complex process may be associated with the transcription of the AnxIcp35 gene and the activation of JAK/STAT and Wnt signal pathways. In this review, we summarize the main components and the biological function of the crop milk, the histological changes of the crop and the regulatory mechanism of crop milk secretion.

  18. Late-stage functionalization of biologically active heterocycles through photoredox catalysis.

    Science.gov (United States)

    Dirocco, Daniel A; Dykstra, Kevin; Krska, Shane; Vachal, Petr; Conway, Donald V; Tudge, Matthew

    2014-05-05

    The direct CH functionalization of heterocycles has become an increasingly valuable tool in modern drug discovery. However, the introduction of small alkyl groups, such as methyl, by this method has not been realized in the context of complex molecule synthesis since existing methods rely on the use of strong oxidants and elevated temperatures to generate the requisite radical species. Herein, we report the use of stable organic peroxides activated by visible-light photoredox catalysis to achieve the direct methyl-, ethyl-, and cyclopropylation of a variety of biologically active heterocycles. The simple protocol, mild reaction conditions, and unique tolerability of this method make it an important tool for drug discovery. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Systems biology in animal sciences.

    Science.gov (United States)

    Woelders, H; Te Pas, M F W; Bannink, A; Veerkamp, R F; Smits, M A

    2011-05-01

    Systems biology is a rapidly expanding field of research and is applied in a number of biological disciplines. In animal sciences, omics approaches are increasingly used, yielding vast amounts of data, but systems biology approaches to extract understanding from these data of biological processes and animal traits are not yet frequently used. This paper aims to explain what systems biology is and which areas of animal sciences could benefit from systems biology approaches. Systems biology aims to understand whole biological systems working as a unit, rather than investigating their individual components. Therefore, systems biology can be considered a holistic approach, as opposed to reductionism. The recently developed 'omics' technologies enable biological sciences to characterize the molecular components of life with ever increasing speed, yielding vast amounts of data. However, biological functions do not follow from the simple addition of the properties of system components, but rather arise from the dynamic interactions of these components. Systems biology combines statistics, bioinformatics and mathematical modeling to integrate and analyze large amounts of data in order to extract a better understanding of the biology from these huge data sets and to predict the behavior of biological systems. A 'system' approach and mathematical modeling in biological sciences are not new in itself, as they were used in biochemistry, physiology and genetics long before the name systems biology was coined. However, the present combination of mass biological data and of computational and modeling tools is unprecedented and truly represents a major paradigm shift in biology. Significant advances have been made using systems biology approaches, especially in the field of bacterial and eukaryotic cells and in human medicine. Similarly, progress is being made with 'system approaches' in animal sciences, providing exciting opportunities to predict and modulate animal traits.

  20. The expanded genetic alphabet.

    Science.gov (United States)

    Malyshev, Denis A; Romesberg, Floyd E

    2015-10-05

    All biological information, since the last common ancestor of all life on Earth, has been encoded by a genetic alphabet consisting of only four nucleotides that form two base pairs. Long-standing efforts to develop two synthetic nucleotides that form a third, unnatural base pair (UBP) have recently yielded three promising candidates, one based on alternative hydrogen bonding, and two based on hydrophobic and packing forces. All three of these UBPs are replicated and transcribed with remarkable efficiency and fidelity, and the latter two thus demonstrate that hydrogen bonding is not unique in its ability to underlie the storage and retrieval of genetic information. This Review highlights these recent developments as well as the applications enabled by the UBPs, including the expansion of the evolution process to include new functionality and the creation of semi-synthetic life that stores increased information. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Expanding Thurston maps

    CERN Document Server

    Bonk, Mario

    2017-01-01

    This monograph is devoted to the study of the dynamics of expanding Thurston maps under iteration. A Thurston map is a branched covering map on a two-dimensional topological sphere such that each critical point of the map has a finite orbit under iteration. It is called expanding if, roughly speaking, preimages of a fine open cover of the underlying sphere under iterates of the map become finer and finer as the order of the iterate increases. Every expanding Thurston map gives rise to a fractal space, called its visual sphere. Many dynamical properties of the map are encoded in the geometry of this visual sphere. For example, an expanding Thurston map is topologically conjugate to a rational map if and only if its visual sphere is quasisymmetrically equivalent to the Riemann sphere. This relation between dynamics and fractal geometry is the main focus for the investigations in this work.

  2. El mosaico de Bernard: la explicación causal en biología funcional = The mosaic of Bernard: cause and effect in functional biology

    Directory of Open Access Journals (Sweden)

    Caponi, Gustavo Andrés

    2014-01-01

    Full Text Available In accordance with a widespread point of view, aligned with the nomological conception of causal explanation, functional biology is subjected to a regime of explanatory heteronomy under which organic phenomena should be explained by using laws of physics and chemistry. Against this perspective, the experimental conception of causation allows us to understand the nature of many biological explanations that, without make any reference to causal laws – physical, chemical or of other nature –, are legitimized because they permit the experimental control of phenomena that have to do with the functioning and development of organisms. These explanations involve local invariants that often, but not necessarily, may be characterized as instances of physical and chemical laws

  3. Re-evaluating concepts of biological function in clinical medicine: towards a new naturalistic theory of disease.

    Science.gov (United States)

    Chin-Yee, Benjamin; Upshur, Ross E G

    2017-08-01

    Naturalistic theories of disease appeal to concepts of biological function, and use the notion of dysfunction as the basis of their definitions. Debates in the philosophy of biology demonstrate how attributing functions in organisms and establishing the function-dysfunction distinction is by no means straightforward. This problematization of functional ascription has undermined naturalistic theories and led some authors to abandon the concept of dysfunction, favoring instead definitions based in normative criteria or phenomenological approaches. Although this work has enhanced our understanding of disease and illness, we need not necessarily abandon naturalistic concepts of function and dysfunction in the disease debate. This article attempts to move towards a new naturalistic theory of disease that overcomes the limitations of previous definitions and offers advantages in the clinical setting. Our approach involves a re-evaluation of concepts of biological function employed by naturalistic theories. Drawing on recent insights from the philosophy of biology, we develop a contextual and evaluative account of function that is better suited to clinical medicine and remains consistent with contemporary naturalism. We also show how an updated naturalistic view shares important affinities with normativist and phenomenological positions, suggesting a possibility for consilience in the disease debate.

  4. Brillouin spectroscopy: a new tool to decipher viscoelastic properties of biological scaffold functionalized with nanoscale films.

    Science.gov (United States)

    Beroud, J; Vincent, B; Paternotte, E; Nguyen, V-S; Kerdjoudj, H; Velot, E; Rouxel, D; Menu, P

    2013-01-01

    In tissue engineering, the endothelialization of vascular scaffold can be a crucial step to improve graft patency. A functional cellularization requires coating surfaces. Since 2003, our group used polyelectrolyte multilayer films (PEMFs) made of poly(allylamine hydrochloride) and polystyren sulfonate to coat luminal surface of blood vessel. Previous results showed that PEMFs have remarkable effect on cellular behavior: adhesion, proliferation, differentiation. However, no method seems adapted for in vitro measurement of the viscoelastic shift after PEMFs buildup. In this present work, we proposed to use a new analytical method based on Brillouin spectroscopy (BS) to investigate the influence PEMFs coating on vessel intrinsic viscoelasticy. On human umbilical arteries and rabbit vessels, PEMFs were buildup and the luminal surfaces viscoelasticy were measuring by BS. It seems that these films do not alter dynamic functionality and BS could be an interesting method for understanding the role of the tissue architecture, the interrelation between the different structures constituting the wall and the influence of this architecture on the tissue behavior, especially with the characterized components of the different vascular wall. The ability of BS to characterize biological samples opens potential applications in tissue engineering field, especially as a tool for a better understanding of vascular diseases.

  5. Dietary Polyphenols as Modulators of Brain Functions: Biological Actions and Molecular Mechanisms Underpinning Their Beneficial Effects

    Science.gov (United States)

    Vauzour, David

    2012-01-01

    Accumulating evidence suggests that diet and lifestyle can play an important role in delaying the onset or halting the progression of age-related health disorders and to improve cognitive function. In particular, polyphenols have been reported to exert their neuroprotective actions through the potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning, and cognitive function. Despite significant advances in our understanding of the biology of polyphenols, they are still mistakenly regarded as simply acting as antioxidants. However, recent evidence suggests that their beneficial effects involve decreases in oxidative/inflammatory stress signaling, increases in protective signaling and neurohormetic effects leading to the expression of genes that encode antioxidant enzymes, phase-2 enzymes, neurotrophic factors, and cytoprotective proteins. Specific examples of such pathways include the sirtuin-FoxO pathway, the NF-κB pathway, and the Nrf-2/ARE pathway. Together, these processes act to maintain brain homeostasis and play important roles in neuronal stress adaptation and thus polyphenols have the potential to prevent the progression of neurodegenerative pathologies. PMID:22701758

  6. Dietary Polyphenols as Modulators of Brain Functions: Biological Actions and Molecular Mechanisms Underpinning Their Beneficial Effects

    Directory of Open Access Journals (Sweden)

    David Vauzour

    2012-01-01

    Full Text Available Accumulating evidence suggests that diet and lifestyle can play an important role in delaying the onset or halting the progression of age-related health disorders and to improve cognitive function. In particular, polyphenols have been reported to exert their neuroprotective actions through the potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning, and cognitive function. Despite significant advances in our understanding of the biology of polyphenols, they are still mistakenly regarded as simply acting as antioxidants. However, recent evidence suggests that their beneficial effects involve decreases in oxidative/inflammatory stress signaling, increases in protective signaling and neurohormetic effects leading to the expression of genes that encode antioxidant enzymes, phase-2 enzymes, neurotrophic factors, and cytoprotective proteins. Specific examples of such pathways include the sirtuin-FoxO pathway, the NF-κB pathway, and the Nrf-2/ARE pathway. Together, these processes act to maintain brain homeostasis and play important roles in neuronal stress adaptation and thus polyphenols have the potential to prevent the progression of neurodegenerative pathologies.

  7. Prospects of innovative functional foods based on biologically active dietary supplement (BADS "VITAZAR"

    Directory of Open Access Journals (Sweden)

    L. E. Glagoleva

    2016-01-01

    Full Text Available The development of syn- and metabiotics is one of the most important technological lines of reserch in the production of functional foods. The positive effect of these products is achieved by the addition of enrichment components into the formulations that provide selective stimulation of the of intestinal normal flora's growth or activates it’s metabolic activity. In this regard, scientific and practical interest seem to study the possibility of expanding the range of synbiotic products containing not less than107 CFU / ml of the probiotic microorganisms on the dairy, vegetable-dairy (protein-free milk, or only on the plant-based medium without dairy ingredients. In the research work we have studied the conditions for the accumulation of biomass of probiotic microorganisms consortium, consisting of L. casei subsp. Rhamnosus, L. acidophilus, L. plantarum, L. fermentum, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium adolescentis on nutrient mediums containing 1-20 % wheat germ flour "Vitazar". The quantitative assessment of the accumulation of probiotic microflora biomass and its metabolites in milk-vitazar based, whey- vitazar based, water-vitazar based nutrient mediums has been carried out . The concentration of Lactobacterium and Bifidobacterium in active form in quantity of 109 CFU / ml has been reached. It was found out that "Vitazar", being a source of dietary fibers and a wide range of carbohydrates, is capable to support the growth of Lactobacterium and Bifidobacterium, forming the favorable environment. The accumulation of probiotic microflora has been observed by the increasing of titratable acidity due to lactose fermentation by β-galactosidase, produced by microorganisms of the consortium. The main stages of the process of the accumulation microbiomass have been identified in the study of the kinetics of the fermentation process. The derived fermented pastes, containing 20 % and 30 % "Vitazar" are

  8. Multi-functional photonic crystal sensors enabled by biological silica (Conference Presentation)

    Science.gov (United States)

    Wang, Alan X.

    2017-02-01

    Diatoms are microalgae found in every habitat where water is present. They produce 40% of the ocean's yearly production of organic carbon and 20% of the oxygen that we breathe. Their abundance and wide distribution make them ideal materials for a wide range of applications as living organisms. In our previous work, we have demonstrated that diatom biosilica with self-assembled silver nanoparticles (Ag NPs) can be used as ultra-sensitive, low-cost substrates for surface-enhanced Raman scattering (SERS) sensing. The enhancement comes from the photonic crystal enhancement of diatom frustules that could improve the hot-spots of Ag NPs. In this work, we report the unique micro-fluidic flow, analyte concentration effect, and thin layer chromatography (TLC) on diatom biosilica, which enables selection, separation, detection, and analysis of complex chemical and biological samples. Particularly, we show that the microscopic fluidic flow induced by the evaporation of liquid droplet can concentrate the analyte and achieve label-free sensing of single molecule detection of R6G and label-free sensing of 4.5×10-17g trinitrotoluene (TNT) from only 200 nano-liter solution. We also demonstrated a facile method for instant on-site separation and detection of analytes by TLC in tandem with SERS spectroscopy using high density diatom thin film. This lab-on-chip technology has been successfully applied for label-free detection of polycyclic aromatic hydrocarbons from human plasma and histamine from salmon fish. Our research suggests that such cost-effective, multi-functional photonic crystal sensors enabled by diatom biosilica opens a new route for lab-on-chip systems and possess significant engineering potentials for chemical and biological sensing.

  9. Structure and functions of water-membrane interfaces and their role in proto-biological evolution

    Science.gov (United States)

    Pohorille, A.; Wilson, M.; Macelroy, R. D.

    1991-01-01

    Among the most important developments in proto-biological evolution was the emergence of membrane-like structures. These are formed by spontaneous association of relatively simple amphiphilic molecules that would have been readily available in the primordial environment. The resulting interfacial regions between water and nonpolar interior of the membrane have several properties which made them uniquely suitable for promoting subsequent evolution. They can (1) selectively attract organic material and mediate its transport, (2) serve as simple catalysts for chemical reactions, and (3) promote the formation of trans-membrane electrical and chemical gradients which could provide energy sources for proto-cells. Understanding the structure of interfaces, their interactions with organic molecules and molecular mechanisms of their functions is an essential step to understanding proto-biological evolution. In our computer simulation studies, we showed that the structure of water at interfaces with nonpolar media is significantly different from that in the bulk. In particular, the average surface dipole density points from the vapor to the liquid. As a result, negative ions can approach the interface more easily than positive ions. Amphiphilic molecules composed of hydrocarbon conjugated rings and polar substituents (e.g., phenol) assume at the interface rigid orientations in which polar groups are buried in water while hydrocarbon parts are located in the nonpolar environment. These orientational differences are of special interest in connection with the ability of some of these molecules to efficiently absorb photons. Flexible molecules with polar substituents often adopt at interfaces conformations different from those in the bulk aquaeous solution and in the gas phase. As a result, in many instances both specificity and kinetics of chemical reactions in which these molecules can participate is modified by the presence of surfaces. Of special interest is the mechanism by

  10. Noninvasive imaging of biological tissue structure, function, and abnormalities with optical coherence tomography

    Science.gov (United States)

    Pan, Yingtian; Lavelle, John; Bastaky, S.; Farkas, Daniel L.; Zeidel, Mark L.

    2000-10-01

    Optical coherence tomography (OCT) is a novel noninvasive optical imaging technique that enables cross-sectional imaging of highly scattering biological tissues at the axial resolution of 10 micrometers or less. Technological advances in our laboratory and others have been permitted high-contrast and high-resolution OCT imaging of turbid biological tissues at depths of up to 2-3 mm, highly desirable for screening various kinds of superficial lesions and the invasion of these lesions. In this study, we will demonstrate the potential of OCT as a powerful tool of optical biopsy or optical guided biopsy for the purpose of noninvasive imaging diagnosing malignancies in these tissues. We will present ex vivo OCT images of animal urinary bladders and lesions (including cancers) in these tissues in comparison with the corresponding histologic evaluations. Based on the comparative studies between OCT and histology, we will analyze the image contrast of OCT or the patterns in OCT images in relation to the micro morphologies in these tissues and their alternations or lesions at different stages of tumorigenesis. We will also analyze the image contrast of OCT related to the blood vessels as well as other tissue functions such as fluid penetration and buildup in these tissues. Our results demonstrate the utility of OCT in high- resolution imaging to delineate the micro morphology of highly scattering tissues such as urinary bladders and the clinical relevance of OCT in diagnosing alternations or tumor growth in these tissues. Because of limitations to specificity and resolution of current techniques, OCT is presently unable to provide distinctive diagnosis of malignancies that require subcellular imaging or identification of subtle changes in nuclear morphology. However, certain characteristics associated with malignancies in bladders such as heavy vascularization and proliferation within the urothelial tissue can be clearly demonstrated.

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

    Directory of Open Access Journals (Sweden)

    Jochen Krauss

    Full Text Available 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

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

    Science.gov (United States)

    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

  13. Understanding human thiol dioxygenase enzymes: structure to function, and biology to pathology.

    Science.gov (United States)

    Sarkar, Bibekananda; Kulharia, Mahesh; Mantha, Anil K

    2017-04-01

    Amino acid metabolism is a significant metabolic activity in humans, especially of sulphur-containing amino acids, methionine and cysteine (Cys). Cys is cytotoxic and neurotoxic in nature; hence, mammalian cells maintain a constant intracellular level of Cys. Metabolism of Cys is mainly regulated by two thiol dioxygenases: cysteine dioxygenase (CDO) and 2-aminoethanethiol dioxygenase (ADO). CDO and ADO are the only human thiol dioxygenases reported with a role in Cys metabolism and localized to mitochondria. This metabolic pathway is important in various human disorders, as it is responsible for the synthesis of antioxidant glutathione and is also for the synthesis of hypotaurine and taurine. CDO is the most extensively studied protein, whose high-resolution crystallographic structures have been solved. As compared to CDO, ADO is less studied, even though it has a key role in cysteamine metabolism. To further understand ADO's structure and function, the three-dimensional structures have been predicted from I-TASSER and SWISS-MODEL servers and validated with PROCHECK software. Structural superimposition approach using iPBA web server further confirmed near-identical structures (including active sites) for the predicted protein models of ADO as compared to CDO. In addition, protein-protein interaction and their association in patho-physiology are crucial in understanding protein functions. Both ADO and CDO interacting partner profiles have been presented using STRING database. In this study, we have predicted a 3D model structure for ADO and summarized the biological roles and the pathological consequences which are associated with the altered expression and functioning of ADO and CDO in case of cancer, neurodegenerative disorders and other human diseases. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

  14. RNA-mediated silencing in Algae: biological roles and tools for analysis of gene function.

    Science.gov (United States)

    Cerutti, Heriberto; Ma, Xinrong; Msanne, Joseph; Repas, Timothy

    2011-09-01

    Algae are a large group of aquatic, typically photosynthetic, eukaryotes that include species from very diverse phylogenetic lineages, from those similar to land plants to those related to protist parasites. The recent sequencing of several algal genomes has provided insights into the great complexity of these organisms. Genomic information has also emphasized our lack of knowledge of the functions of many predicted genes, as well as the gene regulatory mechanisms in algae. Core components of the machinery for RNA-mediated silencing show widespread distribution among algal lineages, but they also seem to have been lost entirely from several species with relatively small nuclear genomes. Complex sets of endogenous small RNAs, including candidate microRNAs and small interfering RNAs, have now been identified by high-throughput sequencing in green, red, and brown algae. However, the natural roles of RNA-mediated silencing in algal biology remain poorly understood. Limited evidence suggests that small RNAs may function, in different algae, in defense mechanisms against transposon mobilization, in responses to nutrient deprivation and, possibly, in the regulation of recently evolved developmental processes. From a practical perspective, RNA interference (RNAi) is becoming a promising tool for assessing gene function by sequence-specific knockdown. Transient gene silencing, triggered with exogenously synthesized nucleic acids, and/or stable gene repression, involving genome-integrated transgenes, have been achieved in green algae, diatoms, yellow-green algae, and euglenoids. The development of RNAi technology in conjunction with system level "omics" approaches may provide the tools needed to advance our understanding of algal physiological and metabolic processes.

  15. Replicating an expanded genetic alphabet in cells.

    Science.gov (United States)

    Chaput, John C

    2014-09-05

    Recent advances in synthetic biology have made it possible to replicate an unnatural base pair in living cells. This study highlights the technologies developed to create a semisynthetic organism with an expanded genetic alphabet and the potential challenges of moving forward. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Silicon microfabricated beam expander

    Energy Technology Data Exchange (ETDEWEB)

    Othman, A., E-mail: aliman@ppinang.uitm.edu.my; Ibrahim, M. N.; Hamzah, I. H.; Sulaiman, A. A. [Faculty of Electrical Engineering, Universiti Teknologi MARA Malaysia, 40450, Shah Alam, Selangor (Malaysia); Ain, M. F. [School of Electrical and Electronic Engineering, Engineering Campus, Universiti Sains Malaysia, Seri Ampangan, 14300,Nibong Tebal, Pulau Pinang (Malaysia)

    2015-03-30

    The feasibility design and development methods of silicon microfabricated beam expander are described. Silicon bulk micromachining fabrication technology is used in producing features of the structure. A high-precision complex 3-D shape of the expander can be formed by exploiting the predictable anisotropic wet etching characteristics of single-crystal silicon in aqueous Potassium-Hydroxide (KOH) solution. The beam-expander consist of two elements, a micromachined silicon reflector chamber and micro-Fresnel zone plate. The micro-Fresnel element is patterned using lithographic methods. The reflector chamber element has a depth of 40 µm, a diameter of 15 mm and gold-coated surfaces. The impact on the depth, diameter of the chamber and absorption for improved performance are discussed.

  17. TRIPLE ACTION PALATE EXPANDER

    Directory of Open Access Journals (Sweden)

    Svetlana Yordanova

    2011-09-01

    Full Text Available Malocclusion correction essentially involves expansion of the maxilla, protrusion of anterior teeth and opening the bite. Expansion is often the stage preceding the treatment with fixed appliances. The elevation of the occlusion using accomplished with different devices (bite planes -fixed or removable, composite material on the occlusall surface of molars carries the risk of breaking or debonding them.The present article proposes an expanding appliance with triple action as a therapeutic means of choice in an orthodontic treatment with fixed appliances. The expander can simultaneously be used to protrude upper teeth, to expand the upper jaw and disarticulate the occlusion. It can be easily fabricated in clinical conditions, causes no discomfort and does not hamper oral hygiene because it can be removed and cleaned.

  18. Carbohydrate/glycan-binding specificity of legume lectins in respect to their proposed biological functions

    Directory of Open Access Journals (Sweden)

    Márcio Viana Ramos

    2000-01-01

    Full Text Available The lectins, proteins which specifically recognize carbohydrate moieties, have been extensively studied in many biochemical and structural aspects in order to establish the molecular basis of this non-catalytic event. On the other hand, their clinical and agricultural potentials have been growing fast. Although lectins, mainly those from legume plants, had been investigated for biological properties, studies about the physiological functions of lectins are scarce in literature. Therefore, despite the accumulated data on lectins (as proteins, the role played by these signalizing molecules is poorly discussed. In the light of our accumulated results on legume lectins, specially those obtained from plants belonging to the Diocleinae sub-tribe and available data in literature, we discuss here the main hypothesis of their functions according to their carbohydrate/glycan-binding specificity.As lectinas, proteinas que especificamente reconhecem estruturas que contém carboidratos, têm sido extensivamente estudadas em muitos aspectos bioquímicos e estruturais, objetivando estabelecer as bases moleculares deste evento não-catalítico. Por outro lado, os potenciais clínicos e agriculturais destas proteínas têm crescido rapidamente. Embora as lectinas, principalmente aquelas de legumes tenham sido bastante investigadas em suas propriedades biológicas, estudos sobre as funcões fisiológicas de lectinas são escassos na literatura. Além disto, a despeito da quantidade de dados acumulados sobre lectinas (como proteínas, o papel desempenhado por estas moléculas de sinalização é pobremente discutido. Valendo-se de nossos estudos sobre lectinas de leguminosas, principalmente da sub-tribo Diocleinae, e outros dados presentes na literatura, discutimos aqui, as principais hipóteses de suas funções com base na especificidade por carboidratos e glicanos complexos.

  19. Nanoparticles improve biological functions of phthalocyanine photosensitizers used for photodynamic therapy.

    Science.gov (United States)

    Jia, Xiao; Jia, Lee

    2012-10-01

    Photodynamic therapy (PDT) is a new technology using photodynamic effect for disease diagnosis and treatment. It is a two-step technique involving the uptake of a photosensitizer by cancer tissue followed by light irradiation that excites the photosensitizer to produce highly reactive oxygen species, the latter execute apoptosis of cancerous cells. As a second-generation of photosensitizers, phthalocyanine demonstrates higher absorption in the 650-800 nm range and short tissue accumulation compared to their first generation. However, many potent phthalocyanine photosensitizers are hydrophobic and poorly water-soluble, which limit their therapeutic applications. As a result, advanced delivery systems and different strategies are called for to improve the effectiveness of PDT. Facts have proved that using nanoparticles as carries of photosensitizers is a very promising route. Nanoparticles have the potentials to increase photosensitizers' aqueous solubility, bioavailability and stability, and deliver photosensitizers to the target tissues. This article reviewed the commonly-used nanoparticles, including colloid gold, quantum dots, paramagnetic nanoparticles, silica-based materials, polymer-based nanoparticles, as potential delivery systems for phthalocyanine photosensitizers, and summarized the improved biological functions of phthalocyanine photosensitizers in PDT.

  20. Biological Redundancy of Endogenous GPCR Ligands in the Gut and the Potential for Endogenous Functional Selectivity

    Directory of Open Access Journals (Sweden)

    Georgina eThompson

    2014-11-01

    Full Text Available This review focuses on the existence and function of multiple endogenous agonists of the somatostatin and opioid receptors with an emphasis on their expression in the gastrointestinal tract (GIT. These agonists generally arise from the proteolytic cleavage of prepropeptides during peptide maturation or from degradation of peptides by extracellular or intracellular endopeptidases. In other examples, endogenous peptide agonists for the same G protein-coupled receptors can be products of distinct genes but contain high sequence homology. This apparent biological redundancy has recently been challenged by the realization that different ligands may engender distinct receptor conformations linked to different intracellular signaling profiles and, as such the existence of distinct ligands may underlie mechanisms to finely tune physiological responses. We propose that further characterization of signaling pathways activated by these endogenous ligands will provide invaluable insight into the mechanisms governing biased agonism. Moreover, these ligands may prove useful in the design of novel therapeutic tools to target distinct signaling pathways, thereby favoring desirable effects and limiting detrimental on-target effects. Finally we will discuss the limitations of this area of research and we will highlight the difficulties that need to be addressed when examining endogenous bias in tissues and in animals.

  1. Non-random distribution of homo-repeats: links with biological functions and human diseases.

    Science.gov (United States)

    Lobanov, Michail Yu; Klus, Petr; Sokolovsky, Igor V; Tartaglia, Gian Gaetano; Galzitskaya, Oxana V

    2016-06-03

    The biological function of multiple repetitions of single amino acids, or homo-repeats, is largely unknown, but their occurrence in proteins has been associated with more than 20 hereditary diseases. Analysing 122 bacterial and eukaryotic genomes, we observed that the number of proteins containing homo-repeats is significantly larger than expected from theoretical estimates. Analysis of statistical significance indicates that the minimal size of homo-repeats varies with amino acid type and proteome. In an attempt to characterize proteins harbouring long homo-repeats, we found that those containing polar or small amino acids S, P, H, E, D, K, Q and N are enriched in structural disorder as well as protein- and RNA-interactions. We observed that E, S, Q, G, L, P, D, A and H homo-repeats are strongly linked with occurrence in human diseases. Moreover, S, E, P, A, Q, D and T homo-repeats are significantly enriched in neuronal proteins associated with autism and other disorders. We release a webserver for further exploration of homo-repeats occurrence in human pathology at http://bioinfo.protres.ru/hradis/.

  2. The biology and functional morphology of Macoma biota (Bivalvia: Tellinidae: Macominae

    Directory of Open Access Journals (Sweden)

    Pedro Ribeiro Piffer

    2011-06-01

    Full Text Available Macoma biota Arruda & Domaneschi, 2005, is a recently described species known only from the intertidal zone of Praia da Cidade, Caraguatatuba Bay, in the state of São Paulo, southeastern Brazil. The main purpose of the present paper is to describe the biology of M. biota, beginning with a detailed analysis of its anatomy and functional morphology and how these attributes are correlated with its habitat and life history. The morphology of the organs in the pallial cavity and their sorting devices indicate that this species has efficient mechanisms to process large amounts of particles that enter this cavity via the inhalant current. M. biota can rapidly select the material suitable for ingestion and direct the undesired excess to the rejection mantle tracts. These characteristics along with the siphon's behavior and the digestive tract configuration reveal that this species can be classified primarily as a deposit feeder, like other species of the genus; however, it can also behave as a suspension feeder, depending on the environmental conditions.

  3. Structure function relationships in the lymphatic system and implications for cancer biology.

    Science.gov (United States)

    Witte, Marlys H; Jones, Kimberly; Wilting, Jörg; Dictor, Michael; Selg, Manuel; McHale, Noel; Gershenwald, Jeffrey E; Jackson, David G

    2006-06-01

    The lymphatic system, composed of lymphatic vessels, lymph, lymph nodes, and lymphocytes, is a distinctive vasculature (discontinuous basement membrane, open endothelial junctions, anchoring filaments, valves, and intrinsic contractility), different yet similar to the blood vasculature; an integral component of the plasma-tissue fluid-lymph circulation (the "blood-lymph loop"); and the center of the immunoregulatory network. Lymphatics are involved in diverse developmental, growth, repair, and pathologic processes both analogous to and distinct from those affecting the blood vasculature. Interference with the blood-lymph loop produces swelling [an imbalance between lymph formation (regulated by Starling's law of transcapillary fluid exchange) and lymph absorption], scarring, nutritional and immunodysregulatory disorders, as well as disturbances in lymph(hem)angiogenesis (lymphedema-angiodysplasia syndromes). The lymphatic system is also the stage on which key events during cancer development and progression are played out, and historically, also forms the basis for current evaluation, prognostication, and/or both operative and non-operative treatment of most cancers. Recent advances in molecular lymphology (e.g., discovery of lymphatic growth factors, endothelial receptors, transcription factors, genes, and highly specific immunohistochemical markers) and growing interest in lymphangiogenesis, combined with fresh insights and refined tools in clinical lymphology, including non-invasive lymphatic imaging, are opening up a window for translation to the clinical arena. Therefore, in cancer biology, attention to the multifaceted structure-function relationships within this vast, relatively unexplored system is long overdue.

  4. Soft robotic arm inspired by the octopus: I. From biological functions to artificial requirements.

    Science.gov (United States)

    Margheri, L; Laschi, C; Mazzolai, B

    2012-06-01

    Octopuses are molluscs that belong to the group Cephalopoda. They lack joints and rigid links, and as a result, their arms possess virtually limitless freedom of movement. These flexible appendages exhibit peculiar biomechanical features such as stiffness control, compliance, and high flexibility and dexterity. Studying the capabilities of the octopus arm is a complex task that presents a challenge for both biologists and roboticists, the latter of whom draw inspiration from the octopus in designing novel technologies within soft robotics. With this idea in mind, in this study, we used new, purposively developed methods of analysing the octopus arm in vivo to create new biologically inspired design concepts. Our measurements showed that the octopus arm can elongate by 70% in tandem with a 23% diameter reduction and exhibits an average pulling force of 40 N. The arm also exhibited a 20% mean shortening at a rate of 17.1 mm s(-1) and a longitudinal stiffening rate as high as 2 N (mm s)(-1). Using histology and ultrasounds, we investigated the functional morphology of the internal tissues, including the sinusoidal arrangement of the nerve cord and the local insertion points of the longitudinal and transverse muscle fibres. The resulting information was used to create novel design principles and specifications that can in turn be used in developing a new soft robotic arm.

  5. Ants: Major Functional Elements in Fruit Agro-Ecosystems and Biological Control Agents

    Directory of Open Access Journals (Sweden)

    Lamine Diamé

    2017-12-01

    Full Text Available Ants are a very diverse taxonomic group. They display remarkable social organization that has enabled them to be ubiquitous throughout the world. They make up approximately 10% of the world’s animal biomass. Ants provide ecosystem services in agrosystems by playing a major role in plant pollination, soil bioturbation, bioindication, and the regulation of crop-damaging insects. Over recent decades, there have been numerous studies in ant ecology and the focus on tree cropping systems has given added importance to ant ecology knowledge. The only missing point in this knowledge is the reasons underlying difference between the positive and negative effects of ants in tree cropping systems. This review article provides an overview of knowledge of the roles played by ants in orchards as functional elements, and on the potential of Oecophylla weaver ants as biological control agents. It also shows the potential and relevance of using ants as an agro-ecological diagnosis tool in orchards. Lastly, it demonstrates the potential elements which may determine the divergent negative and positive of their effects on cropping systems.

  6. Short term recovery of soil biological functions in a new vineyard cultivated in organic farming

    Science.gov (United States)

    Costantini, Edoardo; Agnelli, Alessandro; Fabiani, Arturo; Gagnarli, Elena; Mocali, Stefano; Priori, Simone; Simoni, Sauro; Valboa, Giuseppe

    2014-05-01

    soil biological classes). Physical soil characteristics remained unchanged after the first year from the earthworks and did not change under grass cover. Chemical analysis only indicated a significant effect of earthworks. Over the 2010-2013 period, the new vineyard showed a slight increase of TOC and total N contents; as compared to the old vineyard, it averaged lower TOC and total N, and higher CaCO3 contents, suggesting still evolving equilibrium conditions. Microarthropod analysis showed significant different abundances and communities' structures both by management system and by year, increasing where the land use pressure was reduced by permanent grass cover and along with the aging of vineyard. Though the euedaphic forms, well adapted to soil life, were always rare. Microbiological analysis showed a different structure of eubacterial communities and a lower microbial activity in the new vineyard, especially during 2010-2012. In contrast, significant differences were not observed between the two vineyards in 2013, and grass cover effect was controversial. To sum up, the consequence of deep earthworks on chemical and biological properties were still evident after four years from planting and more time was needed to recover soil functions. Permanent grass cover did not always show a consistent positive effect.

  7. From electron microscopy to molecular cell biology, molecular genetics and structural biology: intracellular transport and kinesin superfamily proteins, KIFs: genes, structure, dynamics and functions.

    Science.gov (United States)

    Hirokawa, Nobutaka

    2011-01-01

    Cells transport and sort various proteins and lipids following synthesis as distinct types of membranous organelles and protein complexes to the correct destination at appropriate velocities. This intracellular transport is fundamental for cell morphogenesis, survival and functioning not only in highly polarized neurons but also in all types of cells in general. By developing quick-freeze electron microscopy (EM), new filamentous structures associated with cytoskeletons are uncovered. The characterization of chemical structures and functions of these new filamentous structures led us to discover kinesin superfamily molecular motors, KIFs. In this review, I discuss the identification of these new structures and characterization of their functions using molecular cell biology and molecular genetics. KIFs not only play significant roles by transporting various cargoes along microtubule rails, but also play unexpected fundamental roles on various important physiological processes such as learning and memory, brain wiring, development of central nervous system and peripheral nervous system, activity-dependent neuronal survival, development of early embryo, left-right determination of our body and tumourigenesis. Furthermore, by combining single-molecule biophysics with structural biology such as cryo-electrom microscopy and X-ray crystallography, atomic structures of KIF1A motor protein of almost all states during ATP hydrolysis have been determined and a common mechanism of motility has been proposed. Thus, this type of studies could be a good example of really integrative multidisciplinary life science in the twenty-first century.

  8. Expandable gastroretentive dosage forms.

    Science.gov (United States)

    Klausner, Eytan A; Lavy, Eran; Friedman, Michael; Hoffman, Amnon

    2003-06-24

    Expandable gastroretentive dosage forms (GRDFs) have been designed for the past 3 decades. They were originally created for possible veterinary use, but later the design was modified for enhanced drug therapy in humans. These GRDFs are easily swallowed and reach a significantly larger size in the stomach due to swelling or unfolding processes that prolong their gastric retention time (GRT). After drug release, their dimensions are minimized with subsequent evacuation from the stomach. Gastroretentivity is enhanced by the combination of substantial dimensions with high rigidity of the dosage form to withstand the peristalsis and mechanical contractility of the stomach. Positive results were obtained in preclinical and clinical studies evaluating GRT of expandable GRDFs. Narrow absorption window drugs compounded in such systems have improved in vivo absorption properties. These findings are an important step towards the implementation of expandable GRDFs in the clinical setting. The current review deals with expandable GRDFs reported in articles and patents, and describes the physiological basis of their design. Using the dog as a preclinical screening model prior to human studies, relevant imaging techniques and pharmacokinetic-pharmacodynamic aspects of such delivery systems are also discussed.

  9. Normative values of functional competence, speed and lower body power for youth football players at different stages of biological maturity

    OpenAIRE

    Ryan, Desmond

    2016-01-01

    Professional football clubs place great emphasis on development of young players to attain first team squad membership, yet despite extensive research on senior teams there is limited knowledge the assessment of functional competence and the development of elite youth players (Brownlee, et al. 2015). This study aimed to assess normative values of functional competence, speed and lower body power for elite youth players at different stages of biological maturity as these factors have significa...

  10. Biosynthesis and metabolism of ?-d-salicin: A novel molecule that exerts biological function in humans and plants

    OpenAIRE

    Jassem G Mahdi

    2014-01-01

    β-d-Salicin 1 (Mahdi et al. [8]) is an interesting medicinal phytochemical that exhibits cross functions in plants and humans immunologically. This molecule 1 (Mahdi et al. [8]) has attracted the attention of scientists in various interdisciplinary fields, including chemistry, pharmacology and medicine. The biological cross functions of β-d-salicin 1 (Mahdi et al. [8]) serve in plant survival and healing processes via salicylic acid 2 (Pierpont [23]). Thus, this raise a question whether plant...

  11. Perchlorate exposure and association with iron homeostasis and other biological functions among NHANES 2005-2008 subjects

    Science.gov (United States)

    Perchlorate exposure and association with iron homeostasis and other biological functions among NHANES 2005-2008 subjects Schreinemachers DM, Ghio AJ, Cascio WE, Sobus JR. U.S. EPA, RTP, NC, USA Perchlorate (ClO4-), an environmental pollutant, is a known thyroid toxicant and...

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

    Science.gov (United States)

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

    2016-11-01

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

  13. Biological oscillations for learning walking coordination: dynamic recurrent neural network functionally models physiological central pattern generator.

    Science.gov (United States)

    Hoellinger, Thomas; Petieau, Mathieu; Duvinage, Matthieu; Castermans, Thierry; Seetharaman, Karthik; Cebolla, Ana-Maria; Bengoetxea, Ana; Ivanenko, Yuri; Dan, Bernard; Cheron, Guy

    2013-01-01

    The existence of dedicated neuronal modules such as those organized in the cerebral cortex, thalamus, basal ganglia, cerebellum, or spinal cord raises the question of how these functional modules are coordinated for appropriate motor behavior. Study of human locomotion offers an interesting field for addressing this central question. The coordination of the elevation of the 3 leg segments under a planar covariation rule (Borghese et al., 1996) was recently modeled (Barliya et al., 2009) by phase-adjusted simple oscillators shedding new light on the understanding of the central pattern generator (CPG) processing relevant oscillation signals. We describe the use of a dynamic recurrent neural network (DRNN) mimicking the natural oscillatory behavior of human locomotion for reproducing the planar covariation rule in both legs at different walking speeds. Neural network learning was based on sinusoid signals integrating frequency and amplitude features of the first three harmonics of the sagittal elevation angles of the thigh, shank, and foot of each lower limb. We verified the biological plausibility of the neural networks. Best results were obtained with oscillations extracted from the first three harmonics in comparison to oscillations outside the harmonic frequency peaks. Physiological replication steadily increased with the number of neuronal units from 1 to 80, where similarity index reached 0.99. Analysis of synaptic weighting showed that the proportion of inhibitory connections consistently increased with the number of neuronal units in the DRNN. This emerging property in the artificial neural networks resonates with recent advances in neurophysiology of inhibitory neurons that are involved in central nervous system oscillatory activities. The main message of this study is that this type of DRNN may offer a useful model of physiological central pattern generator for gaining insights in basic research and developing clinical applications.

  14. [In vivo replacement of phosphatidylethanolamine by phosphatidylcholine affects biological function of E. coli].

    Science.gov (United States)

    Wu, Bin; Ye, Qing; Li, Yang; Li, Changyu; Yu, Xuejing; Zhou, Shu; Wang, Xingguo

    2010-11-01

    We investigated differences in morphology, physiology, periplasmic proteins and phagocytosis by macrophage among E. coli strains AD93 (PE- PC-), AD93/ptac67 (PE- PC+), Top10/ptac66(PE+ PC+) and the wild types in order to understand if phosphatidylcholine (PC) can substitute phosphatidylethanolamine (PE) in vivo. Bacterial cells were observed under microscope after staining with Gram-staining kit or by electron microscope. Bacterial growth under different conditions was monitored by measuring the absorbance at the wavelength of 600 nm. Periplasmic proteins were analyzed using SDS-PAGE and 2-D electrophoresis. Bacterial adherence and phagocytosis by macrophage were also examined by using murine RAW264.7 macrophage. 100% bacterial cells in AD93/pDD72 were bar-shaped but 25% AD93/ptac67 cells came out as long filaments. Different from AD93/ pDD72, AD93/ptac67 and AD93 required Mg2+ or Ca2+ for growth. Moreover, AD93/ptac67 displayed a different pattern of periplasmic proteins on a 2-D gel and a low relatively phagocytic efficiency in the phagocytosis test when compared to AD93/pDD72 and AD93. Both Top10/ptac66 and the wild-type Top10/ptac85 cells were bar-shaped under microscope, but the former showed noticeably difference in the outer-layer structure of cell wall, and its stress resistance and periplasmic protein composition were also different from those of the latter. Substitution of phosphatidylethanolamine with phosphatidylcholine in E. coli cells is unable to restore the phonotype of PE- mutant to the wild type. Biological functions of PE and PC are different, and phosphatidylcholine cannot substitute phosphatidylethanolamine in vivo.

  15. Functional near infrared spectroscopy as a potential biological assessment of addiction recovery: preliminary findings.

    Science.gov (United States)

    Dempsey, Jared P; Harris, Kitty S; Shumway, Sterling T; Kimball, Thomas G; Herrera, J Caleb; Dsauza, Cynthia M; Bradshaw, Spencer D

    2015-03-01

    Addiction science has primarily utilized self-report, continued substance use, and relapse factors to explore the process of recovery. However, the entry into successful abstinence substantially reduces our assessment abilities. Advances in neuroscience may be the key to objective understanding, treating, and monitoring long-term success in addiction recovery. To explore functional near infrared spectroscopy (fNIR) as a viable technique in the assessment of addiction-cue reactivity. Specifically, prefrontal cortex (PFC) activation to alcohol cues was explored among formally alcohol-dependent individuals, across varying levels of successful abstinence. The aim of the investigation was to identify patterns of PFC activation change consistent with duration of abstinence. A total of 15 formally alcohol-dependent individuals, with abstinence durations ranging from 1 month to 10 years, viewed alcohol images during fNIR PFC assessment. Participants also subjectively rated the same images for affect and arousal level. Subjective ratings of alcohol cues did not significantly correlate with duration of abstinence. As expected, days of abstinence did not significantly correlate with neutral cue fNIR reactivity. However, for alcohol cues, fNIR results showed increased days of abstinence was associated with decreased activation within the dorsolateral and dorsomedial prefrontal cortex regions. The present results suggest that fNIR may be a viable tool in the assessment of addiction-cue reactivity. RESULTS also support previous findings on the importance of dorsolateral and dorsomedial PFC in alcohol-cue activation. The findings build upon these past results suggesting that fNIR-assessed activation may represent a robust biological marker of successful addiction recovery.

  16. The development of peptide-based interfacial biomaterials for generating biological functionality on the surface of bioinert materials.

    Science.gov (United States)

    Meyers, Steven R; Khoo, Xiaojuan; Huang, Xin; Walsh, Elisabeth B; Grinstaff, Mark W; Kenan, Daniel J

    2009-01-01

    Biomaterials used in implants have traditionally been selected based on their mechanical properties, chemical stability, and biocompatibility. However, the durability and clinical efficacy of implantable biomedical devices remain limited in part due to the absence of appropriate biological interactions at the implant interface and the lack of integration into adjacent tissues. Herein, we describe a robust peptide-based coating technology capable of modifying the surface of existing biomaterials and medical devices through the non-covalent binding of modular biofunctional peptides. These peptides contain at least one material binding sequence and at least one biologically active sequence and thus are termed, "Interfacial Biomaterials" (IFBMs). IFBMs can simultaneously bind the biomaterial surface while endowing it with desired biological functionalities at the interface between the material and biological realms. We demonstrate the capabilities of model IFBMs to convert native polystyrene, a bioinert surface, into a bioactive surface that can support a range of cell activities. We further distinguish between simple cell attachment with insufficient integrin interactions, which in some cases can adversely impact downstream biology, versus biologically appropriate adhesion, cell spreading, and cell survival mediated by IFBMs. Moreover, we show that we can use the coating technology to create spatially resolved patterns of fluorophores and cells on substrates and that these patterns retain their borders in culture.

  17. Systems Biology and Health Systems Complexity in;

    NARCIS (Netherlands)

    Donald Combs, C.; Barham, S.R.; Sloot, P.M.A.

    2016-01-01

    Systems biology addresses interactions in biological systems at different scales of biological organization, from the molecular to the cellular, organ, organism, societal, and ecosystem levels. This chapter expands on the concept of systems biology, explores its implications for individual patients

  18. Grazing incidence beam expander

    Energy Technology Data Exchange (ETDEWEB)

    Akkapeddi, P.R.; Glenn, P.; Fuschetto, A.; Appert, Q.; Viswanathan, V.K.

    1985-01-01

    A Grazing Incidence Beam Expander (GIBE) telescope is being designed and fabricated to be used as an equivalent end mirror in a long laser resonator cavity. The design requirements for this GIBE flow down from a generic Free Electron Laser (FEL) resonator. The nature of the FEL gain volume (a thin, pencil-like, on-axis region) dictates that the output beam be very small. Such a thin beam with the high power levels characteristic of FELs would have to travel perhaps hundreds of meters or more before expanding enough to allow reflection from cooled mirrors. A GIBE, on the other hand, would allow placing these optics closer to the gain region and thus reduces the cavity lengths substantially. Results are presented relating to optical and mechanical design, alignment sensitivity analysis, radius of curvature analysis, laser cavity stability analysis of a linear stable concentric laser cavity with a GIBE. Fabrication details of the GIBE are also given.

  19. Expanding the HAWC Observatory

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Johanna [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-17

    The High Altitude Water Cherenkov Gamma-Ray Observatory is expanding its current array of 300 water tanks to include 350 outrigger tanks to increase sensitivity to gamma rays above 10 TeV. This involves creating and testing hardware with which to build the new tanks, including photomultiplier tubes, high voltage supply units, and flash analog to digital converters. My responsibilities this summer included preparing, testing and calibrating that equipment.

  20. Antisense oligodeoxynucleotide inhibition as a potent diagnostic tool for gene function in plant biology

    Energy Technology Data Exchange (ETDEWEB)

    Jansson, Christer; Sun, Chuanxin; Ghebramedhin, Haile; Hoglund, Anna-Stina; Jansson, Christer

    2008-01-15

    Antisense oligodeoxynucleotide (ODN) inhibition emerges as an effective means for probing gene function in plant cells. Employing this method we have established the importance of the SUSIBA2 transcription factor for regulation of starch synthesis in barley endosperm, and arrived at a model for the role of the SUSIBAs in sugar signaling and source-sink commutation during cereal endosperm development. In this addendum we provide additional data demonstrating the suitability of the antisense ODN technology in studies on starch branching enzyme activities in barley leaves. We also comment on the mechanism for ODN uptake in plant cells. Antisense ODNs are short (12-25 nt-long) stretches of single-stranded ODNs that hybridize to the cognate mRNA in a sequence-specific manner, thereby inhibiting gene expression. They are naturally occurring in both prokaryotes and eukaryotes where they partake in gene regulation and defense against viral infection. The mechanisms for antisense ODN inhibition are not fully understood but it is generally considered that the ODN either sterically interferes with translation or promotes transcript degradation by RNase H activation. The earliest indication of the usefulness of antisense ODN technology for the purposes of molecular biology and medical therapy was the demonstration in 1978 that synthetic ODNs complementary to Raos sarcoma virus could inhibit virus replication in tissue cultures of chick embryo fibroblasts. Since then the antisense ODN technology has been widely used in animal sciences and as an important emerging therapeutic approach in clinical medicine. However, antisense ODN inhibition has been an under-exploited strategy for plant tissues, although the prospects for plant cells in suspension cultures to take up single-stranded ODNs was reported over a decade ago. In 2001, two reports from Malho and coworker demonstrated the use of cationic-complexed antisense ODNs to suppress expression of genes encoding pollen

  1. The Protein Corona of PEGylated PGMA-Based Nanoparticles is Preferentially Enriched with Specific Serum Proteins of Varied Biological Function.

    Science.gov (United States)

    Naidu, Priya S R; Norret, Marck; Smith, Nicole M; Dunlop, Sarah A; Taylor, Nicolas L; Fitzgerald, Melinda; Iyer, K Swaminathan

    2017-11-14

    The composition of the protein corona formed on poly(ethylene glycol)-functionalized (PEGylated) poly(glycidyl methacrylate) (PGMA) nanoparticles (NPs) was qualitatively and quantitatively compared to the protein corona on non-PEGylated PGMA NPs. Despite the reputation of PEGylated NPs for stealth functionality, we demonstrate the preferential enrichment of specific serum proteins of varied biological function in the protein corona on PEGylated NPs when compared to non-PEGylated NPs. Additionally, we suggest that the base material of polymeric NPs plays a role in the preferential enrichment of select serum proteins to the hard corona.

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

    Science.gov (United States)

    Dewhurst, Henry; Sundararaman, Niveda

    2016-01-01

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

  3. A Functional Model for Teaching Osmosis-Diffusion to Biology Students

    Science.gov (United States)

    Olsen, Richard W.; Petry, Douglas E.

    1976-01-01

    Described is a maternal-fetal model, operated by the student, to teach osmosis-diffusion to biology students. Included are materials needed, assembly instructions, and student operating procedures. (SL)

  4. Enhancing microbial production of biofuels by expanding microbial metabolic pathways.

    Science.gov (United States)

    Yu, Ping; Chen, Xingge; Li, Peng

    2017-09-01

    Fatty acid, isoprenoid, and alcohol pathways have been successfully engineered to produce biofuels. By introducing three genes, atfA, adhE, and pdc, into Escherichia coli to expand fatty acid pathway, up to 1.28 g/L of fatty acid ethyl esters can be achieved. The isoprenoid pathway can be expanded to produce bisabolene with a high titer of 900 mg/L in Saccharomyces cerevisiae. Short- and long-chain alcohols can also be effectively biosynthesized by extending the carbon chain of ketoacids with an engineered "+1" alcohol pathway. Thus, it can be concluded that expanding microbial metabolic pathways has enormous potential for enhancing microbial production of biofuels for future industrial applications. However, some major challenges for microbial production of biofuels should be overcome to compete with traditional fossil fuels: lowering production costs, reducing the time required to construct genetic elements and to increase their predictability and reliability, and creating reusable parts with useful and predictable behavior. To address these challenges, several aspects should be further considered in future: mining and transformation of genetic elements related to metabolic pathways, assembling biofuel elements and coordinating their functions, enhancing the tolerance of host cells to biofuels, and creating modular subpathways that can be easily interconnected. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

  5. Expanding the genetic heterogeneity of intellectual disability

    KAUST Repository

    Anazi, Shams

    2017-09-22

    Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

  6. Expanding the genetic heterogeneity of intellectual disability.

    Science.gov (United States)

    Anazi, Shams; Maddirevula, Sateesh; Salpietro, Vincenzo; Asi, Yasmine T; Alsahli, Saud; Alhashem, Amal; Shamseldin, Hanan E; AlZahrani, Fatema; Patel, Nisha; Ibrahim, Niema; Abdulwahab, Firdous M; Hashem, Mais; Alhashmi, Nadia; Al Murshedi, Fathiya; Al Kindy, Adila; Alshaer, Ahmad; Rumayyan, Ahmed; Al Tala, Saeed; Kurdi, Wesam; Alsaman, Abdulaziz; Alasmari, Ali; Banu, Selina; Sultan, Tipu; Saleh, Mohammed M; Alkuraya, Hisham; Salih, Mustafa A; Aldhalaan, Hesham; Ben-Omran, Tawfeg; Al Musafri, Fatima; Ali, Rehab; Suleiman, Jehan; Tabarki, Brahim; El-Hattab, Ayman W; Bupp, Caleb; Alfadhel, Majid; Al Tassan, Nada; Monies, Dorota; Arold, Stefan T; Abouelhoda, Mohamed; Lashley, Tammaryn; Houlden, Henry; Faqeih, Eissa; Alkuraya, Fowzan S

    2017-11-01

    Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

  7. [THE FUNCTIONAL CONSTITUENT OF A BIOLOGICAL COMPONENT IN PROGRAMS FOR TRAINING SPECIALISTS IN THE AREA OF PARASITOLOGY FOR ACCREDITATION].

    Science.gov (United States)

    Dovgalev, A S; Astanina, S Yu; Andreeva, N D

    2015-01-01

    The paper considers the functional aspects of a biological component in programs for training specialists in the area of Parasitology for accreditation within the current enactments, including those on modernization of public health and additional professional education. The working program of the module "Fundamental Disciplines" has been used as an example to outline approaches to molding a medical parasitologist's capacity and readiness to solve professional tasks on the basis of knowledge of fundamental disciplines: biology, immunology, and medical geography. Education fundamentalization is shown to suggest more unsupervised work of a learner in the teaching process. The fundamental constituent of a biological component of the 'programs for training learners in the specialty of Parasitology for accreditation is shown in the interaction of all sections of this area with special and allied subjects.

  8. Holistic systems biology approaches to molecular mechanisms of human helper T cell differentiation to functionally distinct subsets.

    Science.gov (United States)

    Chen, Z; Lönnberg, T; Lahesmaa, R

    2013-08-01

    Current knowledge of helper T cell differentiation largely relies on data generated from mouse studies. To develop therapeutical strategies combating human diseases, understanding the molecular mechanisms how human naïve T cells differentiate to functionally distinct T helper (Th) subsets as well as studies on human differentiated Th cell subsets is particularly valuable. Systems biology approaches provide a holistic view of the processes of T helper differentiation, enable discovery of new factors and pathways involved and generation of new hypotheses to be tested to improve our understanding of human Th cell differentiation and immune-mediated diseases. Here, we summarize studies where high-throughput systems biology approaches have been exploited to human primary T cells. These studies reveal new factors and signalling pathways influencing T cell differentiation towards distinct subsets, important for immune regulation. Such information provides new insights into T cell biology and into targeting immune system for therapeutic interventions. © 2013 John Wiley & Sons Ltd.

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

    Science.gov (United States)

    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.

  10. Coral Reef Health Indices versus the Biological, Ecological and Functional Diversity of Fish and Coral Assemblages in the Caribbean Sea.

    Science.gov (United States)

    Díaz-Pérez, Leopoldo; Rodríguez-Zaragoza, Fabián Alejandro; Ortiz, Marco; Cupul-Magaña, Amílcar Leví; Carriquiry, Jose D; Ríos-Jara, Eduardo; Rodríguez-Troncoso, Alma Paola; García-Rivas, María Del Carmen

    2016-01-01

    This study evaluated the relationship between the indices known as the Reef Health Index (RHI) and two-dimensional Coral Health Index (2D-CHI) and different representative metrics of biological, ecological and functional diversity of fish and corals in 101 reef sites located across seven zones in the western Caribbean Sea. Species richness and average taxonomic distinctness were used to asses biological estimation; while ecological diversity was evaluated with the indices of Shannon diversity and Pielou´s evenness, as well as by taxonomic diversity and distinctness. Functional diversity considered the number of functional groups, the Shannon diversity and the functional Pielou´s evenness. According to the RHI, 57.15% of the zones were classified as presenting a "poor" health grade, while 42.85% were in "critical" grade. Based on the 2D-CHI, 28.5% of the zones were in "degraded" condition and 71.5% were "very degraded". Differences in fish and coral diversity among sites and zones were demonstrated using permutational ANOVAs. Differences between the two health indices (RHI and 2D-CHI) and some indices of biological, ecological and functional diversity of fish and corals were observed; however, only the RHI showed a correlation between the health grades and the species and functional group richness of fish at the scale of sites, and with the species and functional group richness and Shannon diversity of the fish assemblages at the scale of zones. None of the health indices were related to the metrics analyzed for the coral diversity. In general, our study suggests that the estimation of health indices should be complemented with classic community indices, or should at least include diversity indices of fish and corals, in order to improve the accuracy of the estimated health status of coral reefs in the western Caribbean Sea.

  11. Human Peroxiredoxins 1 and 2 and Their Interacting Protein Partners; Through Structure Toward Functions of Biological Complexes.

    Science.gov (United States)

    Bertoldi, Mariarita

    2016-01-01

    Since their discovery in the mid-nineties, peroxiredoxins have drawn much attention and the number of papers publications on different Prxs has been multiplied. The rise in interest in this topic is probably due, at least in part, to the large and further increasing functions attributed to the members of this family of ubiquitous proteins, including many redox and non-redox physiological functions. This review presents a Since their discovery in the mid-nineties, peroxiredoxins have drawn much attention and the number of publications on different Prxs has been multiplied. The rise in interest in this topic is probably due, at least in part, to the large and further increasing functions attributed to the members of this family of ubiquitous proteins, including many redox and non-redox physiological functions. This review presents a literature survey of the protein partners of the human Peroxiredoxin-1 and Peroxiredoxin- 2 of the Peroxiredoxin 1 subfamily, the most abundant class. Three sequence motifs, or combinations thereof, were found in the protein partners, namely, CXXC, PXXP, and LXXLL. These findings are discussed in light of i) protein partner localization, function and biological pathways and ii) the peroxiredoxins regions important for partner interaction, as revealed by the Peroxiredoxin-1-Sulfiredoxin-1 complex structure. The outcome of these analyses is expected to unravel some common molecular bases underlying peroxiredoxins propensity to bind a partner, as well as to propose a functional role for this interaction that could help to widen the biological role of this important class of enzymes.

  12. The expanding universe

    CERN Document Server

    Lew, Kristi

    2011-01-01

    People have always been fascinated with the stars above and the universe that contains them. Over the years, astronomers have developed numerous theories to explain how the universe began, how it works, and what its ultimate fate will be. But all of the scientists' questions are far from answered. The Expanding Universe goes beyond the creation of the universe to explain how scientists think the universe works, grows, and changes, including what great thinkers Isaac Newton and Albert Einstein had to say about its fate. Readers will also learn about how researchers are slowly shedding light on

  13. Expanding Your Horizon 2015

    CERN Multimedia

    Kaltenhauser, Kristin

    2015-01-01

    Expanding your horizons is a bi-annual “Science Day” for girls aged 11 to 14, held at the University of Geneva on 14 November. The girls had the opportunity to take part in hands-on workshops held by local professional women in the field of science, mathematics, engineering and technology. For the fourth time, CERN was part of this event, offering three workshops as well as a booth at the Discovery Fair, including Higgnite, an interactive visualization of the Higgs Field.

  14. Structural and functional diversity among amyloid proteins: Agents of disease, building blocks of biology, and implications for molecular engineering.

    Science.gov (United States)

    Bleem, Alissa; Daggett, Valerie

    2017-01-01

    Amyloids have long been associated with protein dysfunction and neurodegenerative diseases, but recent research has demonstrated that some organisms utilize the unique properties of the amyloid fold to create functional structures with important roles in biological processes. Additionally, new engineering approaches have taken advantage of amyloid structures for implementation in a wide variety of materials and devices. In this review, the role of amyloid in human disease is discussed and compared to the functional amyloids, which serve a largely structural purpose. We then consider the use of amyloid constructs in engineering applications, including their utility as building blocks for synthetic biology and molecular engineering. Biotechnol. Bioeng. 2017;114: 7-20. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Thyroid Autoimmunity and Function after Treatment with Biological Antirheumatic Agents in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Bliddal, Sofie; Dinsen, Stina; Feldt-Rasmussen, Ulla

    2017-01-01

    With the increased pro-inflammatory response in both rheumatoid arthritis and thyroid autoimmune diseases, treatment with biological antirheumatic agents (BAAs) of the former may affect the course of the latter. In hepatitis C and cancer patients, treatment with biological agents substantially...... increases the risk of developing thyroid autoimmunity. As the use of BAAs in the treatment of rheumatoid arthritis is increasing, this review aimed to investigate if such use affected thyroid status in rheumatoid arthritis patients. We conducted a systematic literature search and included six studies...

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

    OpenAIRE

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

    2016-01-01

    Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the priori...

  17. Myxoma virus protein M029 is a dual function immunomodulator that inhibits PKR and also conscripts RHA/DHX9 to promote expanded host tropism and viral replication.

    Directory of Open Access Journals (Sweden)

    Masmudur M Rahman

    Full Text Available Myxoma virus (MYXV-encoded protein M029 is a member of the poxvirus E3 family of dsRNA-binding proteins that antagonize the cellular interferon signaling pathways. In order to investigate additional functions of M029, we have constructed a series of targeted M029-minus (vMyx-M029KO and vMyx-M029ID and V5-tagged M029 MYXV. We found that M029 plays a pivotal role in determining the cellular tropism of MYXV in all mammalian cells tested. The M029-minus viruses were able to replicate only in engineered cell lines that stably express a complementing protein, such as vaccinia E3, but underwent abortive or abated infection in all other tested mammalian cell lines. The M029-minus viruses were dramatically attenuated in susceptible host European rabbits and caused no observable signs of myxomatosis. Using V5-tagged M029 virus, we observed that M029 expressed as an early viral protein is localized in both the nuclear and cytosolic compartments in virus-infected cells, and is also incorporated into virions. Using proteomic approaches, we have identified Protein Kinase R (PKR and RNA helicase A (RHA/DHX9 as two cellular binding partners of M029 protein. In virus-infected cells, M029 interacts with PKR in a dsRNA-dependent manner, while binding with DHX9 was not dependent on dsRNA. Significantly, PKR knockdown in human cells rescued the replication defect of the M029-knockout viruses. Unexpectedly, this rescue of M029-minus virus replication by PKR depletion could then be reversed by RHA/DHX9 knockdown in human monocytic THP1 cells. This indicates that M029 not only inhibits generic PKR anti-viral pathways, but also binds and conscripts RHA/DHX9 as a pro-viral effector to promote virus replication in THP1 cells. Thus, M029 is a critical host range and virulence factor for MYXV that is required for replication in all mammalian cells by antagonizing PKR-mediated anti-viral functions, and also conscripts pro-viral RHA/DHX9 to promote viral replication

  18. Myxoma virus protein M029 is a dual function immunomodulator that inhibits PKR and also conscripts RHA/DHX9 to promote expanded host tropism and viral replication.

    Science.gov (United States)

    Rahman, Masmudur M; Liu, Jia; Chan, Winnie M; Rothenburg, Stefan; McFadden, Grant

    2013-01-01

    Myxoma virus (MYXV)-encoded protein M029 is a member of the poxvirus E3 family of dsRNA-binding proteins that antagonize the cellular interferon signaling pathways. In order to investigate additional functions of M029, we have constructed a series of targeted M029-minus (vMyx-M029KO and vMyx-M029ID) and V5-tagged M029 MYXV. We found that M029 plays a pivotal role in determining the cellular tropism of MYXV in all mammalian cells tested. The M029-minus viruses were able to replicate only in engineered cell lines that stably express a complementing protein, such as vaccinia E3, but underwent abortive or abated infection in all other tested mammalian cell lines. The M029-minus viruses were dramatically attenuated in susceptible host European rabbits and caused no observable signs of myxomatosis. Using V5-tagged M029 virus, we observed that M029 expressed as an early viral protein is localized in both the nuclear and cytosolic compartments in virus-infected cells, and is also incorporated into virions. Using proteomic approaches, we have identified Protein Kinase R (PKR) and RNA helicase A (RHA)/DHX9 as two cellular binding partners of M029 protein. In virus-infected cells, M029 interacts with PKR in a dsRNA-dependent manner, while binding with DHX9 was not dependent on dsRNA. Significantly, PKR knockdown in human cells rescued the replication defect of the M029-knockout viruses. Unexpectedly, this rescue of M029-minus virus replication by PKR depletion could then be reversed by RHA/DHX9 knockdown in human monocytic THP1 cells. This indicates that M029 not only inhibits generic PKR anti-viral pathways, but also binds and conscripts RHA/DHX9 as a pro-viral effector to promote virus replication in THP1 cells. Thus, M029 is a critical host range and virulence factor for MYXV that is required for replication in all mammalian cells by antagonizing PKR-mediated anti-viral functions, and also conscripts pro-viral RHA/DHX9 to promote viral replication specifically in myeloid

  19. FUNCTION IN BIOLOGY: ETIOLOGICAL AND ORGANIZATIONAL PERSPECTIVES Función en Biología: perspectivas etiológicas y organizacionales

    Directory of Open Access Journals (Sweden)

    CHARBEL NIÑO EL-HANI

    Full Text Available In this paper, we argue for a taxonomy of approaches to function based on different epistemological perspectives assumed with regard to the treatment of this central concept in the life sciences. We distinguish between etiological and organizational perspectives on function, analyzing distinct theories: Wright's selectionist etiological approach and Godfrey-Smith's modern history theory of functions, in the case of the etiological perspective; and Cummins' functional analysis and Collier's interactivist approach to function, among organizational accounts. We explain differences and similarities between these theories and the broader perspectives on function, arguing for a particular way of understanding the consensus without unity in debates about function. While explaining the accounts of function, we also deal with the relationship between this concept and other important biological concepts, such as adaptation, selection, complexity, and autonomy. We also advance an argument for the limits and prospects of the explanatory role of function in evolution. By arguing that changes in functionality are always grounded on changes in systems' organization, we show that function can never explain the origins of traits. Nevertheless, it can explain the spread of traits in populations, but only when we are dealing with functionally novel traits. Finally, we stress that organizational accounts of function are needed to understand how new functions appear by means of changes in systems' organization.En este artículo, argumentamos a favor de una taxonomía de abordajes del concepto función basada en diferentes perspectivas epistemológicas de acuerdo al tratamiento de este concepto central en las ciencias de la vida. Distinguimos entre perspectivas etiológicas y organizacionales sobre la noción de función, analizando teorías distintas: la teoría etiológica seleccionista de Wright y la teoría de la historia moderna de Godfrey-Smith, en el caso de

  20. Wearable functional near infrared spectroscopy (fNIRS) and transcranial direct current stimulation (tDCS): expanding vistas for neurocognitive augmentation.

    Science.gov (United States)

    McKendrick, Ryan; Parasuraman, Raja; Ayaz, Hasan

    2015-01-01

    Contemporary studies with transcranial direct current stimulation (tDCS) provide a growing base of evidence for enhancing cognition through the non-invasive delivery of weak electric currents to the brain. The main effect of tDCS is to modulate cortical excitability depending on the polarity of the applied current. However, the underlying mechanism of neuromodulation is not well understood. A new generation of functional near infrared spectroscopy (fNIRS) systems is described that are miniaturized, portable, and include wearable sensors. These developments provide an opportunity to couple fNIRS with tDCS, consistent with a neuroergonomics approach for joint neuroimaging and neurostimulation investigations of cognition in complex tasks and in naturalistic conditions. The effects of tDCS on complex task performance and the use of fNIRS for monitoring cognitive workload during task performance are described. Also explained is how fNIRS + tDCS can be used simultaneously for assessing spatial working memory. Mobile optical brain imaging is a promising neuroimaging tool that has the potential to complement tDCS for realistic applications in natural settings.

  1. Wearable functional Near Infrared Spectroscopy (fNIRS and transcranial Direct Current Stimulation (tDCS: Expanding Vistas for Neurocognitive Augmentation

    Directory of Open Access Journals (Sweden)

    Ryan eMcKendrick

    2015-03-01

    Full Text Available Contemporary studies with transcranial direct current stimulation (tDCS provide a growing base of evidence for enhancing cognition through the non-invasive delivery of weak electric currents to the brain. The main effect of tDCS is to modulate cortical excitability depending on the polarity of the applied current. However, the underlying mechanism of neuromodulation is not well understood. A new generation of functional near infrared spectroscopy (fNIRS systems is described that are miniaturized, portable, and include wearable sensors. These developments provide an opportunity to couple fNIRS with tDCS, consistent with a neuroergonomics approach for joint neuroimaging and neurostimulation investigations of cognition in complex tasks and in naturalistic conditions. The effects of tDCS on complex task performance and the use of fNIRS for monitoring cognitive workload during task performance are described. Also explained is how fNIRS + tDCS can be used simultaneously for assessing spatial working memory. Mobile optical brain imaging is a promising neuroimaging tool that has the potential to complement tDCS for realistic applications in natural settings.

  2. Antagonistic roles of abscisic acid and cytokinin during response to nitrogen depletion in oleaginous microalga Nannochloropsis oceanica expand the evolutionary breadth of phytohormone function.

    Science.gov (United States)

    Lu, Yandu; Tarkowská, Danuše; Turečková, Veronika; Luo, Tingwei; Xin, Yi; Li, Jing; Wang, Qintao; Jiao, Nianzhi; Strnad, Miroslav; Xu, Jian

    2014-10-01

    The origin of phytohormones is poorly understood, and their physiological roles in microalgae remain elusive. Genome comparison of photosynthetic autotrophic eukaryotes has revealed that the biosynthetic pathways of abscisic acid (ABA) and cytokinins (CKs) emerged in unicellular algae. While ABA and CK degradation mechanisms emerged broadly in algal lineages, complete vascular plant-type conjugation pathways emerged prior to the rise of Streptophyta. In microalgae, a complete set of proteins from the canonical ABA and CK sensing and signaling pathways is not essential, but individual components are present, suggesting stepwise recruitment of phytohormone signaling components. In the oleaginous eustigmatophyte Nannochloropsis oceanica IMET1, UHPLC-MS/MS detected a wide array of plant hormones, despite a phytohormone profile that is very distinct from that of flowering plants. Time-series transcriptional analysis during nitrogen depletion revealed activation of the ABA biosynthetic pathway and antagonistic transcription of CK biosynthetic genes. Correspondingly, the ABA level increases while the dominant bioactive CK forms decrease. Moreover, exogenous CKs stimulate cell-cycle progression while exogenous ABA acts as both an algal growth repressor and a positive regulator in response to stresses. The presence of such functional flowering plant-like phytohormone signaling systems in Nannochloropsis sp. suggests a much earlier origin of phytohormone biosynthesis and degradation than previously believed, and supports the presence in microalgae of as yet unknown conjugation and sensing/signaling systems that may be exploited for microalgal feedstock development. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  3. Calibration of the Modulation Transfer Function of Surface Profilometers with Binary Pseudorandom Test Standards: Expanding the Application Range to Fizeau Interferometers and Electron Microscopes

    Energy Technology Data Exchange (ETDEWEB)

    Yashchuk, V.V.; Takacs, P.; Anderson, E.H.; Barber, S.K.; Bouet, N.; Cambie, R.; Conley, R.; McKinney, W.R.; Voronov, D.L.

    2011-09-16

    A modulation transfer function (MTF) calibration method based on binary pseudorandom (BPR) gratings and arrays has been proven to be an effective MTF calibration method for interferometric microscopes and a scatterometer. Here we report on a further expansion of the application range of the method. We describe the MTF calibration of a 6 in. phase shifting Fizeau interferometer. Beyond providing a direct measurement of the interferometer's MTF, tests with a BPR array surface have revealed an asymmetry in the instrument's data processing algorithm that fundamentally limits its bandwidth. Moreover, the tests have illustrated the effects of the instrument's detrending and filtering procedures on power spectral density measurements. The details of the development of a BPR test sample suitable for calibration of scanning and transmission electron microscopes are also presented. Such a test sample is realized as a multilayer structure with the layer thicknesses of two materials corresponding to the BPR sequence. The investigations confirm the universal character of the method that makes it applicable to a large variety of metrology instrumentation with spatial wavelength bandwidths from a few nanometers to hundreds of millimeters.

  4. N-acylation of phosphatidylethanolamine and its biological functions in mammals

    DEFF Research Database (Denmark)

    Wellner, Niels; Diep, Thi Ai; Janfelt, Christian

    2013-01-01

    N-acylphosphatidylethanolamine (NAPE) and N-acylplasmenylethanolamine (pNAPE) are widely found phospholipids, and they are precursors for N-acylethanolamines, a group of compounds that has a variety of biological effects and encompasses the endocannabinoid anandamide. NAPE and pNAPE are synthesiz...

  5. Functionalization and microfluidic integration of silicon nanowire biologically gated field effect transistors

    DEFF Research Database (Denmark)

    Pfreundt, Andrea; Svendsen, Winnie Edith; Dimaki, Maria

    2016-01-01

    This thesis deals with the development of a novel biosensor for the detection of biomolecules based on a silicon nanowire biologically gated field-effect transistor and its integration into a point-of-care device. The sensor and electrical on-chip integration was developed in a different project...

  6. Functionalization and microfluidic integration of silicon nanowire biologically gated field effect transistors

    DEFF Research Database (Denmark)

    Pfreundt, Andrea

    This thesis deals with the development of a novel biosensor for the detection of biomolecules based on a silicon nanowire biologically gated field-effect transistor and its integration into a point-of-care device. The sensor and electrical on-chip integration was developed in a different project...

  7. Discovering and validating biological hypotheses from coherent patterns in functional genomics data

    Energy Technology Data Exchange (ETDEWEB)

    Joachimiak, Marcin Pawel

    2008-08-12

    The area of transcriptomics analysis is among the more established in computational biology, having evolved in both technology and experimental design. Transcriptomics has a strong impetus to develop sophisticated computational methods due to the large amounts of available whole-genome datasets for many species and because of powerful applications in regulatory network reconstruction as well as elucidation and modeling of cellular transcriptional responses. While gene expression microarray data can be noisy and comparisons across experiments challenging, there are a number of sophisticated methods that aid in arriving at statistically and biologically significant conclusions. As such, computational transcriptomics analysis can provide guidance for analysis of results from newer experimental technologies. More recently, search methods have been developed to identify modules of genes, which exhibit coherent expression patterns in only a subset of experimental conditions. The latest advances in these methods allow to integrate multiple data types anddatasets, both experimental and computational, within a single statistical framework accounting for data confidence and relevance to specific biological questions. Such frameworks provide a unified environment for the exploration of specific biological hypothesis and for the discovery of coherent data patterns along with the evidence supporting them.

  8. Enabling Web-Based GIS Tools for Internet and Mobile Devices To Improve and Expand NASA Data Accessibility and Analysis Functionality for the Renewable Energy and Agricultural Applications

    Science.gov (United States)

    Ross, A.; Stackhouse, P. W.; Tisdale, B.; Tisdale, M.; Chandler, W.; Hoell, J. M., Jr.; Kusterer, J.

    2014-12-01

    The NASA Langley Research Center Science Directorate and Atmospheric Science Data Center have initiated a pilot program to utilize Geographic Information System (GIS) tools that enable, generate and store climatological averages using spatial queries and calculations in a spatial database resulting in greater accessibility of data for government agencies, industry and private sector individuals. The major objectives of this effort include the 1) Processing and reformulation of current data to be consistent with ESRI and openGIS tools, 2) Develop functions to improve capability and analysis that produce "on-the-fly" data products, extending these past the single location to regional and global scales. 3) Update the current web sites to enable both web-based and mobile application displays for optimization on mobile platforms, 4) Interact with user communities in government and industry to test formats and usage of optimization, and 5) develop a series of metrics that allow for monitoring of progressive performance. Significant project results will include the the development of Open Geospatial Consortium (OGC) compliant web services (WMS, WCS, WFS, WPS) that serve renewable energy and agricultural application products to users using GIS software and tools. Each data product and OGC service will be registered within ECHO, the Common Metadata Repository, the Geospatial Platform, and Data.gov to ensure the data are easily discoverable and provide data users with enhanced access to SSE data, parameters, services, and applications. This effort supports cross agency, cross organization, and interoperability of SSE data products and services by collaborating with DOI, NRCan, NREL, NCAR, and HOMER for requirements vetting and test bed users before making available to the wider public.

  9. Mechanical and biological properties of the micro-/nano-grain functionally graded hydroxyapatite bioceramics for bone tissue engineering.

    Science.gov (United States)

    Zhou, Changchun; Deng, Congying; Chen, Xuening; Zhao, Xiufen; Chen, Ying; Fan, Yujiang; Zhang, Xingdong

    2015-08-01

    Functionally graded materials (FGM) open the promising approach for bone tissue repair. In this study, a novel functionally graded hydroxyapatite (HA) bioceramic with micrograin and nanograin structure was fabricated. Its mechanical properties were tailored by composition of micrograin and nanograin. The dynamic mechanical analysis (DMA) indicated that the graded HA ceramics had similar mechanical property compared to natural bones. Their cytocompatibility was evaluated via fluorescent microscopy and MTT colorimetric assay. The viability and proliferation of rabbit bone marrow mesenchymal stem cells (BMSCs) on ceramics indicated that this functionally graded HA ceramic had better cytocompatibility than conventional HA ceramic. This study demonstrated that functionally graded HA ceramics create suitable structures to satisfy both the mechanical and biological requirements of bone tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Bayesian uncertainty analysis for complex systems biology models: emulation, global parameter searches and evaluation of gene functions.

    Science.gov (United States)

    Vernon, Ian; Liu, Junli; Goldstein, Michael; Rowe, James; Topping, Jen; Lindsey, Keith

    2018-01-02

    Many mathematical models have now been employed across every area of systems biology. These models increasingly involve large numbers of unknown parameters, have complex structure which can result in substantial evaluation time relative to the needs of the analysis, and need to be compared to observed data of various forms. The correct analysis of such models usually requires a global parameter search, over a high dimensional parameter space, that incorporates and respects the most important sources of uncertainty. This can be an extremely difficult task, but it is essential for any meaningful inference or prediction to be made about any biological system. It hence represents a fundamental challenge for the whole of systems biology. Bayesian statistical methodology for the uncertainty analysis of complex models is introduced, which is designed to address the high dimensional global parameter search problem. Bayesian emulators that mimic the systems biology model but which are extremely fast to evaluate are embeded within an iterative history match: an efficient method to search high dimensional spaces within a more formal statistical setting, while incorporating major sources of uncertainty. The approach is demonstrated via application to a model of hormonal crosstalk in Arabidopsis root development, which has 32 rate parameters, for which we identify the sets of rate parameter values that lead to acceptable matches between model output and observed trend data. The multiple insights into the model's structure that this analysis provides are discussed. The methodology is applied to a second related model, and the biological consequences of the resulting comparison, including the evaluation of gene functions, are described. Bayesian uncertainty analysis for complex models using both emulators and history matching is shown to be a powerful technique that can greatly aid the study of a large class of systems biology models. It both provides insight into model behaviour

  11. Biological Soil Crusts Influence Hydrologic Function Differently in Various Deserts And Future Climate and Land Use will Affect These Relationships

    Science.gov (United States)

    Belnap, J.; Wilcox, B.; Barger, N.; Herrick, J.; van Soyoc, M.

    2012-04-01

    Biological soil crusts (biocrusts) can completely cover plant interspaces in dryland regions, and can constitute 70% or more of the living ground cover. In these areas, where precipitation is low and soils have low fertility, native plants often rely on intact biological soil crusts to provide water and nutrient flow to the broadly scattered vegetation. In cool desert systems, well-developed biocrusts (dominated by lichens and mosses) roughen the soil surface, increasing residence time of surface water flow. This results in increased and relatively homogenous infiltration of water into the soils. Filaments associated with cyanobacteria, fungi, mosses and lichens increase aggregate formation and stabilize soils, thus reducing sediment production, with well-developed biocrusts conferring much more stability on soils than less developed cyanobacterial dominated biocrusts. In hot and hyper-arid desert systems, biocrusts are generally less developed and dominated by cyanobacteria. These biocrusts generally increase runoff from plant interspaces to downslope vegetation. While reduced infiltration may seem to be negative, it can actually be advantageous to the downslope plants, as they may require small watersheds above them to provide the needed amount of water and nutrients required for their growth. Thus, infiltration and nutrient additions are more heterogenous than in cool desert systems. Soil surface disturbance and climate change have the potential to dramatically alter the species composition and thereby function of biological soil crusts in different deserts. Compressional disturbances results in reduced cover and a loss of lichen and moss species. Changes in climate regimes, such as an increase in temperature or a shift in the amount, timing, or intensity of rainfall, will influence the composition and physiological functioning of biological soil crusts, as various crust components have different photosynthetic and respiration responses to temperature and

  12. Expanding hollow metal rings

    Science.gov (United States)

    Peacock, Harold B [Evans, GA; Imrich, Kenneth J [Grovetown, GA

    2009-03-17

    A sealing device that may expand more planar dimensions due to internal thermal expansion of a filler material. The sealing material is of a composition such that when desired environment temperatures and internal actuating pressures are reached, the sealing materials undergoes a permanent deformation. For metallic compounds, this permanent deformation occurs when the material enters the plastic deformation phase. Polymers, and other materials, may be using a sealing mechanism depending on the temperatures and corrosivity of the use. Internal pressures are generated by either rapid thermal expansion or material phase change and may include either liquid or solid to gas phase change, or in the gaseous state with significant pressure generation in accordance with the gas laws. Sealing material thickness and material composition may be used to selectively control geometric expansion of the seal such that expansion is limited to a specific facing and or geometric plane.

  13. Preventive Ethics Through Expanding Education.

    Science.gov (United States)

    Ho, Anita; MacDonald, Lisa Mei-Hwa; Unger, David

    2016-03-01

    Healthcare institutions have been making increasing efforts to standardize consultation methodology and to accredit both bioethics training programs and the consultants accordingly. The focus has traditionally been on the ethics consultation as the relevant unit of ethics intervention. Outcome measures are studied in relation to consultations, and the hidden assumption is that consultations are the preferred or best way to address day-to-day ethical dilemmas. Reflecting on the data from an internal quality improvement survey and the literature, we argue that having general ethics education as a key function of ethics services may be more important in meeting the contemporaneous needs of acute care settings. An expanded and varied ethics education, with attention to the time constraints of healthcare workers' schedules, was a key recommendation brought forward by survey respondents. Promoting ethical reflection and creating a culture of ethics may serve to prevent ethical dilemmas or mitigate their effects.

  14. Recent Progress in Synthesis and Functionalization of Multimodal Fluorescent-Magnetic Nanoparticles for Biological Applications

    Directory of Open Access Journals (Sweden)

    Raquel Serrano García

    2018-01-01

    Full Text Available There is a great interest in the development of new nanomaterials for multimodal imaging applications in biology and medicine. Multimodal fluorescent-magnetic based nanomaterials deserve particular attention as they can be used as diagnostic and drug delivery tools, which could facilitate the diagnosis and treatment of cancer and many other diseases. This review focuses on the recent developments of magnetic-fluorescent nanocomposites and their biomedical applications. The recent advances in synthetic strategies and approaches for the preparation of fluorescent-magnetic nanocomposites are presented. The main biomedical uses of multimodal fluorescent-magnetic nanomaterials, including biological imaging, cancer therapy and drug delivery, are discussed, and prospects of this field are outlined.

  15. The Bioethicist Who Cried "Synthetic Biology": An Analysis of the Function of Bioterrorism Predictions in Bioethics.

    Science.gov (United States)

    Holm, Søren

    2017-04-01

    This article analyzes a specter that has haunted bioethics almost since its inception, namely the specter of the misuse of biotechnology by maleficent agents bent on mass destruction, or the complete eradication of human kind and life as we know it. The article provides a general account of why bioethicists cry "catastrophic bioterrorism potential" when new biotechnologies emerge, and an analysis of the arguments that flow from the prediction, especially in relation to synthetic biology.

  16. Adolescent risk-taking as a function of prenatal cocaine exposure and biological sex.

    Science.gov (United States)

    Allen, Jedediah W P; Bennett, David S; Carmody, Dennis P; Wang, Yiping; Lewis, Michael

    2014-01-01

    To examine the effects of prenatal cocaine exposure and biological sex on adolescent risk-taking while controlling for early environmental risk. Adolescents (n=114, mean age=16) were grouped according to high and low risk-taking propensity as measured by the Balloon Analogue Risk Task (BART). Prenatal cocaine exposure was assessed at birth, while environmental risk was assessed at three points during early childhood. A binary regression analysis indicated that males were 3.5 times more likely than females to be high risk-takers. Biological sex and prenatal cocaine exposure interacted such that exposed males were most likely to be high risk-takers while exposed females were the least likely to be high risk-takers. This pattern held after controlling for prenatal alcohol exposure and early environmental risk. Early environmental risk did not predict adolescent risk-taking. These findings complement and extend earlier research demonstrating that prenatal cocaine exposure interacts with biological sex in domains related to inhibitory control, emotion regulation, antisocial behavior, and health risk behaviors during preadolescence. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Estimation of relevant variables on high-dimensional biological patterns using iterated weighted kernel functions.

    Directory of Open Access Journals (Sweden)

    Sergio Rojas-Galeano

    2008-03-01

    Full Text Available The analysis of complex proteomic and genomic profiles involves the identification of significant markers within a set of hundreds or even thousands of variables that represent a high-dimensional problem space. The occurrence of noise, redundancy or combinatorial interactions in the profile makes the selection of relevant variables harder.Here we propose a method to select variables based on estimated relevance to hidden patterns. Our method combines a weighted-kernel discriminant with an iterative stochastic probability estimation algorithm to discover the relevance distribution over the set of variables. We verified the ability of our method to select predefined relevant variables in synthetic proteome-like data and then assessed its performance on biological high-dimensional problems. Experiments were run on serum proteomic datasets of infectious diseases. The resulting variable subsets achieved classification accuracies of 99% on Human African Trypanosomiasis, 91% on Tuberculosis, and 91% on Malaria serum proteomic profiles with fewer than 20% of variables selected. Our method scaled-up to dimensionalities of much higher orders of magnitude as shown with gene expression microarray datasets in which we obtained classification accuracies close to 90% with fewer than 1% of the total number of variables.Our method consistently found relevant variables attaining high classification accuracies across synthetic and biological datasets. Notably, it yielded very compact subsets compared to the original number of variables, which should simplify downstream biological experimentation.

  18. Functional Genomic Investigation of the Molecular Biological Impact of Electron Beam Radiation in Lymphoma Cells.

    Science.gov (United States)

    Gopal, Ramani; Rani, Usha; Murugesan, Ram; Kumar, Kirushna; Sanjeev, Ganesh; Ganesan, Kumaresan

    2016-05-01

    The biological response of electron beam radiation (EBR) in tumors remains underexplored. This study describes the molecular biological and genomic impact of EBR on tumor cells. A mouse model bearing Dalton's lymphoma ascites cells was exposed to an 8-MeV pulsed electron beam, at a dose rate of 2 Gy/min using a microtron, a linear accelerator. The radiation-induced changes were assessed by histopathology, fluorescence-activated cell sorting, signaling pathway-focused reporter assays, and gene expression by microarray analysis. EBR was found to increase apoptosis and G2-M cell cycle arrest with concomitant tumor regression in vivo. The microarray data revealed that EBR induced tumor regression, apoptosis, and cell cycle arrest mediated by p53, PPAR, and SMAD2/3/4 signaling pathways. Activation of interferon regulatory factor and NFkB signaling were also found upon EBR. Chemo-genomics exploration revealed the possibility of drugs that can be effectively used in combination with EBR. For the first time, an 8-MeV pulse EBR induced genomic changes, and their consequence in molecular and biological processes were identified in lymphoma cells. The comprehensive investigation of radiation-mediated responses in cancer cells also revealed the potential therapeutic features of EBR. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Human Dopamine Receptors Interaction Network (DRIN): a systems biology perspective on topology, stability and functionality of the network.

    Science.gov (United States)

    Podder, Avijit; Jatana, Nidhi; Latha, N

    2014-09-21

    Dopamine receptors (DR) are one of the major neurotransmitter receptors present in human brain. Malfunctioning of these receptors is well established to trigger many neurological and psychiatric disorders. Taking into consideration that proteins function collectively in a network for most of the biological processes, the present study is aimed to depict the interactions between all dopamine receptors following a systems biology approach. To capture comprehensive interactions of candidate proteins associated with human dopamine receptors, we performed a protein-protein interaction network (PPIN) analysis of all five receptors and their protein partners by mapping them into human interactome and constructed a human Dopamine Receptors Interaction Network (DRIN). We explored the topology of dopamine receptors as molecular network, revealing their characteristics and the role of central network elements. More to the point, a sub-network analysis was done to determine major functional clusters in human DRIN that govern key neurological pathways. Besides, interacting proteins in a pathway were characterized and prioritized based on their affinity for utmost drug molecules. The vulnerability of different networks to the dysfunction of diverse combination of components was estimated under random and direct attack scenarios. To the best of our knowledge, the current study is unique to put all five dopamine receptors together in a common interaction network and to understand the functionality of interacting proteins collectively. Our study pinpointed distinctive topological and functional properties of human dopamine receptors that have helped in identifying potential therapeutic drug targets in the dopamine interaction network. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Expanding cosmic horizons of life

    Science.gov (United States)

    Wickramasinghe, Nalin C.; Narlikar, J. V.; Wickramasinghe, J. T.; Wainwright, Milton

    2003-02-01

    The conceptual boundaries of life are rapidly expanding far beyond the confines of our planet to encompass an ever-widening region of the universe. Complex organic molecules in interstellar dust and comets appear most plausibly to be biologically derived, or at least closely related spectroscopically and structurally to such material. A de novo origin of life from non-living material is reckoned to have so minuscule a probability that its occurrence once in the universe can be considered miracle enough. The widespread distribution of similar material (e.g with the characteristics of the diffuse infrared bands and 2175 absorption features) throughout the galaxy and in external galaxies adds weight to the theory of panspermia, where it is supposed that the components of life at a generic level are readily transferred from one place to another. Spectroscopic evidence consistent with life extends to redshifts z=0.5, and from elemental abundance studies alone (e.g, of C, O and metals) in distant galaxies the possibility of cosmic life extends to redshifts as high as z=3.

  1. From transcriptome to biological function: environmental stress in an ectothermic vertebrate, the coral reef fish Pomacentrus moluccensis

    Directory of Open Access Journals (Sweden)

    Ward Alister C

    2007-10-01

    Full Text Available Abstract Background Our understanding of the importance of transcriptional regulation for biological function is continuously improving. We still know, however, comparatively little about how environmentally induced stress affects gene expression in vertebrates, and the consistency of transcriptional stress responses to different types of environmental stress. In this study, we used a multi-stressor approach to identify components of a common stress response as well as components unique to different types of environmental stress. We exposed individuals of the coral reef fish Pomacentrus moluccensis to hypoxic, hyposmotic, cold and heat shock and measured the responses of approximately 16,000 genes in liver. We also compared winter and summer responses to heat shock to examine the capacity for such responses to vary with acclimation to different ambient temperatures. Results We identified a series of gene functions that were involved in all stress responses examined here, suggesting some common effects of stress on biological function. These common responses were achieved by the regulation of largely independent sets of genes; the responses of individual genes varied greatly across different stress types. In response to heat exposure over five days, a total of 324 gene loci were differentially expressed. Many heat-responsive genes had functions associated with protein turnover, metabolism, and the response to oxidative stress. We were also able to identify groups of co-regulated genes, the genes within which shared similar functions. Conclusion This is the first environmental genomic study to measure gene regulation in response to different environmental stressors in a natural population of a warm-adapted ectothermic vertebrate. We have shown that different types of environmental stress induce expression changes in genes with similar gene functions, but that the responses of individual genes vary between stress types. The functions of heat

  2. Systems biology in animal sciences

    OpenAIRE

    Woelders, H.; Pas, te, M.F.W.; Bannink, A.; Veerkamp, R. F.; Smits, M A

    2011-01-01

    Systems biology is a rapidly expanding field of research and is applied in a number of biological disciplines. In animal sciences, omics approaches are increasingly used, yielding vast amounts of data, but systems biology approaches to extract understanding from these data of biological processes and animal traits are not yet frequently used. This paper aims to explain what systems biology is and which areas of animal sciences could benefit from systems biology approaches. Systems biology aim...

  3. Superclusters : a search for novel structures and functions of biological iron-sulfur clusters

    NARCIS (Netherlands)

    Arendsen, A.F.

    1996-01-01


    Iron sulfur (Fe-S) proteins are found in a variety of organisms. They usually function in electron transport, but they may also be involved in other functions like gene regulation and Lewis acid catalysis. The structure and spectroscopic properties of Fe-S clusters holding one, two,

  4. Functionalization of Self-Organized Nanoparticles for Biological Targeting and Active Drug Release

    DEFF Research Database (Denmark)

    Jølck, Rasmus Irming

    surface density after post-functionalization is highly important, to ensure batch-to-batch reproducibility and to ensure that the desired ligand surface density has been accomplished. A systematic study was furthermore conducted to elucidate the optimal post-functionalization chemistry, in addition...

  5. Sulfonated graphenes catalyzed synthesis of expanded porphyrins ...

    Indian Academy of Sciences (India)

    A newer synthesis of sulfonic acid functionalized graphenes have been developed, which have been characterized, examined as heterogeneous solid acid carbocatalyst in the synthesis of selected expanded porphyrins in different reaction conditions. This environment-friendly catalyst avoids the use of toxic catalysts and ...

  6. Sulfonated graphenes catalyzed synthesis of expanded porphyrins ...

    Indian Academy of Sciences (India)

    Abstract. A newer synthesis of sulfonic acid functionalized graphenes have been developed, which have been characterized, examined as heterogeneous solid acid carbocatalyst in the synthesis of selected expanded porphyrins in different reaction conditions. This environment-friendly catalyst avoids the use of toxic ...

  7. Virtual Agonist-antagonist Mechanisms Produce Biological Muscle-like Functions: An Application for Robot Joint Control

    DEFF Research Database (Denmark)

    Xiong, Xiaofeng; Wörgötter, Florentin; Manoonpong, Poramate

    2014-01-01

    or torque sensing systems; thereby capable of implementing the model on small legged robots driven by, e.g., standard servo motors. Thus, the VAAM minimizes hardware and reduces system complexity. From this point of view, the model opens up another way of simulating muscle behaviors on artificial machines......Purpose – Biological muscles of animals have a surprising variety of functions, i.e., struts, springs, and brakes. According to this, the purpose of this paper is to apply virtual agonist-antagonist mechanisms to robot joint control allowing for muscle-like functions and variably compliant joint...... motions. Design/methodology/approach – Each joint is driven by a pair of virtual agonist-antagonist mechanism (VAAM, i.e., passive components). The muscle-like functions as well as the variable joint compliance are simply achieved by tuning the damping coefficient of the VAAM. Findings – With the VAAM...

  8. Harmonic oscillators: the quantization of simple systems in the old quantum theory and their functional roles in biology.

    Science.gov (United States)

    Steele, Richard H

    2008-03-01

    This article introduces quantum physics into biology in an intuitive and non-intimidating manner. It extends the quantum aspects of harmonic oscillators, and electromagnetic fields, to their functional roles in biology. Central to this process are the De Broglie wave-particle duality equation, and the adiabatic invariant parameters, magnetic moment, angular momentum and magnetic flux, determined by Ehrenfest as imposing quantum constraints on the dynamics of charges in motion. In mechanisms designed to explain the generation of low-level light emissions in biology we have adopted a biological analog of the electrical circuitry modeled on the parallel plated capacitor, traversed by helical protein structures, capable of generating electromagnetic radiation in the optical spectral region. The charge carrier required for the emissions is an accelerating electron driven, in a cyclotron-type mechanism, by ATP-induced reverse electron transfer with the radial, emission, components, mediated by coulombic forces within the helical configurations. Adenine, an essential nucleotide constituent of DNA, was examined with its long wavelength absorption maximum determining the energetic parameters for the calculations. The calculations were made for a virtual 5-turn helix where each turn of the helix emits a different frequency, generating a biological quantum series. The components of six adiabatic invariant equations were found to be embedded in Planck's constant rendering them discrete, finite, non-random, non-statistical-Planck's constant precludes probability. A mechanism for drug-induced hallucination is described that might provide insights as to the possible role of electromagnetic fields in consciousness. Sodium acceleration through a proposed nerve membrane helical channel generated electromagnetic emissions in the microwave region in confirmation of reported microwave emission for active nerves and may explain saltatory nerve conduction. Theoretical calculations for a

  9. Biological half-life of iodine in adults with intact thyroid function and in athyreotic persons

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, G.H.; Hauck, B.M.; Chamberlain, M.J

    2002-07-01

    A joint project between the Human Monitoring Laboratory (HML) and the Ottawa Hospital has measured the retention of {sup 131}I in patients who have received the radioiodine diagnostically. Thirty-nine subjects with intact thyroid glands and nine athyreotic subjects were measured in the HML's whole-body/thyroid counter to determine the retention of {sup 131}I following its medical administration. The average biological half-life of {sup 131}I in 26 euthyroid subjects was found to be 66.1{+-}6.3 days which may be statistically significantly lower than the ICRP recommended value of 80 days. Nine hyperthyroid patients had a mean biological half-life of 38.2{+-}8.6 days and in three hypothyroid patients the corresponding value was 29.3{+-}8.8 days. Thyroid {sup 131}I uptake was measured in a conventional clinical fashion at the Ottawa Hospital Civic campus 24 h after oral administration of the radioiodine using a collimated thick sodium iodide detector placed over the neck arteriorly. Measured values were 0.144{+-}0.009, 0.314{+-}0.035 and 0.045{+-}0.010 of the administered dose in euthyroid, hyperthyroid and hypothyroid patients respectively. The euthyroid range at the hospital is 0.06-0.22. Uptake was significantly lower for the euthyroid group than the ICRP value of 0.3. The radioiodine retention in athyreotic subjects followed a two compartment model with biological half-lives of 1.0{+-}0.2 days and 18.4{+-}1.1. days. (author)

  10. Dual mode diffraction phase microscopy for quantitative functional assessment of biological cells

    Science.gov (United States)

    Talaikova, N. A.; Popov, A. P.; Kalyanov, A. L.; Ryabukho, V. P.; Meglinski, I. V.

    2017-10-01

    A diffraction phase microscopy approach with a combined use of transmission and reflection imaging modes has been developed and applied for non-invasive quantitative assessment of the refractive index of red blood cells (RBCs). We present the theoretical background of signal formation for both imaging modes, accompanied by the results of experimental studies. We demonstrate that simultaneous use of the two modes has great potential for accurate assessment of the refractive index of biological cells, and we perform a reconstruction of spatial distribution of the refractive index of RBC in 3D.

  11. The counter ion: expanding excipient functionality

    Directory of Open Access Journals (Sweden)

    Shireesh Apte

    2011-06-01

    Full Text Available Excipients have increasingly become 'enablers' of drug delivery and efficacy rather than passive bystanders. Advances in pharmaceutical technology have enabled the ability to deliver specific counter ions (in the form of the counter ion containing excipient and the API simultaneously to preselected targets in the body. This, coupled with a near universal mechanism of columbic interactions that determine the [API- counter ion] efficacy, can be harnessed to exploit this hitherto unavailable or unrecognized enabling mechanism. New excipients may be assembled by a near inexhaustible supply of different permutations of counter ions and their judicious use in specific situations could potentially drive a renaissance in excipient innovation (and drug delivery and efficacy despite regulatory stagnation.

  12. [The unity of image recognition of tolite homothetic receptors and glycosylation end product receptors in biologic function in case of diabetes].

    Science.gov (United States)

    Titov, V N; Shiriaeva, Iu K

    2011-08-01

    In compliance with our theory of biologic functions and reactions, pathogenesis of all diseases in formed in the framework of disorder of seven biologic functions: trophology, homeostasis, endoecology, adaptation, locomotion, genus continuation and intelligence. The disorder of biologic function of endoecology ("purity" of intercellular medium in vivo) is the most common basis of pathogenesis of diseases' nosological forms. There are two methods of elimination of disorder of this function. First is the biological reaction of excretion i.e. the removal of minor endogenic phlogogenes (initiators of inflammation) with molecular weightless than 70 amu. The second is the biological function of inflammation i.e. utilization of large endogenic phlogogenes (more than 70 amu) by means of phagocytosis of functional phagocytes. The inherent and acquired immunity are other biological reactions of biological function of endoecology. They overlap with biological reaction of transcytosis and biological reaction of hydrodynamic pressure activating transcytosis. The system of tolite homothetic receptors discriminating molecules of native proteins and endogenic phlogogenes on principle "right-wrong" is the basis of biological function of inherent immunity. In case of hyperglycemia and diabetes glucose becomes the minor biological "refuse". The products of chemical reaction between glucose and proteins and formation of the end products of glycosylation, components of areolar tissue become the major biological "refuse". The accumulation of products of glycosylation of collagen with cross-links in capillaries' wall increases its rigidity and makes it impossible for pericytes to implement the qualities of primary peristaltic pump. Hence the formation of hypoperfusion, condition of hypoxemia in microcirculatory section of blood circulation (muscular type arteriolae, postateriolae with muscular sphincter, metabolic capillaries) resulting in the development of microangiopathies of distal

  13. Developments in the Tools and Methodologies of Synthetic Biology

    Science.gov (United States)

    Kelwick, Richard; MacDonald, James T.; Webb, Alexander J.; Freemont, Paul

    2014-01-01

    Synthetic biology is principally concerned with the rational design and engineering of biologically based parts, devices, or systems. However, biological systems are generally complex and unpredictable, and are therefore, intrinsically difficult to engineer. In order to address these fundamental challenges, synthetic biology is aiming to unify a “body of knowledge” from several foundational scientific fields, within the context of a set of engineering principles. This shift in perspective is enabling synthetic biologists to address complexity, such that robust biological systems can be designed, assembled, and tested as part of a biological design cycle. The design cycle takes a forward-design approach in which a biological system is specified, modeled, analyzed, assembled, and its functionality tested. At each stage of the design cycle, an expanding repertoire of tools is being developed. In this review, we highlight several of these tools in terms of their applications and benefits to the synthetic biology community. PMID:25505788

  14. Expander chunked codes

    Science.gov (United States)

    Tang, Bin; Yang, Shenghao; Ye, Baoliu; Yin, Yitong; Lu, Sanglu

    2015-12-01

    Chunked codes are efficient random linear network coding (RLNC) schemes with low computational cost, where the input packets are encoded into small chunks (i.e., subsets of the coded packets). During the network transmission, RLNC is performed within each chunk. In this paper, we first introduce a simple transfer matrix model to characterize the transmission of chunks and derive some basic properties of the model to facilitate the performance analysis. We then focus on the design of overlapped chunked codes, a class of chunked codes whose chunks are non-disjoint subsets of input packets, which are of special interest since they can be encoded with negligible computational cost and in a causal fashion. We propose expander chunked (EC) codes, the first class of overlapped chunked codes that have an analyzable performance, where the construction of the chunks makes use of regular graphs. Numerical and simulation results show that in some practical settings, EC codes can achieve rates within 91 to 97 % of the optimum and outperform the state-of-the-art overlapped chunked codes significantly.

  15. Reaction mechanism interplay in determining the biological effectiveness of neutrons as a function of energy.

    Science.gov (United States)

    Baiocco, G; Alloni, D; Babini, G; Mariotti, L; Ottolenghi, A

    2015-09-01

    Neutron relative biological effectiveness (RBE) is found to be energy dependent, being maximal for energies ∼1 MeV. This is reflected in the choice of radiation weighting factors wR for radiation protection purposes. In order to trace back the physical origin of this behaviour, a detailed study of energy deposition processes with their full dependences is necessary. In this work, the Monte Carlo transport code PHITS was used to characterise main secondary products responsible for energy deposition in a 'human-sized' soft tissue spherical phantom, irradiated by monoenergetic neutrons with energies around the maximal RBE/wR. Thereafter, results on the microdosimetric characterisation of secondary protons were used as an input to track structure calculations performed with PARTRAC, thus evaluating the corresponding DNA damage induction. Within the proposed simplified approach, evidence is suggested for a relevant role of secondary protons in inducing the maximal biological effectiveness for 1 MeV neutrons. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Closed-form equation to estimate the dielectric properties of biological tissues as a function of age.

    Science.gov (United States)

    Mohammed, Beadaa; Bialkowski, Konstanty; Abbosh, Amin; Mills, Paul C; Bradley, Andrew P

    2017-09-01

    Developing microwave systems for biomedical applications requires accurate dielectric properties of biological tissues for reliable modeling before prototyping and subject testing. Dielectric properties of tissues decrease with age due to the change in their water content, but there are no detailed age-dependent data, especially for young tissue-like newborns, in the literature. In this article, an age-dependent formula to predict the dielectric properties of biological tissues was derived. In the proposed method, the variation of water concentration in each type of tissue as a function of age was used to calculate its relative permittivity and conductivity. The derived formula shows that the concentration of water in each tissue type can be modeled as a negative exponential function of age. The dielectric properties of each tissue type can then be calculated as a function of the dielectric properties of water and dielectric properties of the organ forming the tissue and its water concentration. The derived formula was used to generate the dielectric properties of several types of human tissues at different ages using the dielectric properties of a human adult. Moreover, the formula was validated on pig tissues of different ages. A close agreement was achieved between the calculated and measured data with a maximum difference of only 2%. Bioelectromagnetics. 38:474-481, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Biological functioning of PAH-polluted and thermal desorption-treated soils assessed by fauna and microbial bioindicators.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  19. Minimal information: an urgent need to assess the functional reliability of recombinant proteins used in biological experiments

    Directory of Open Access Journals (Sweden)

    de Marco Ario

    2008-07-01

    Full Text Available Abstract Structural characterization of proteins used in biological experiments is largely neglected. In most publications, the information available is totally insufficient to judge the functionality of the proteins used and, therefore, the significance of identified protein-protein interactions (was the interaction specific or due to unspecific binding of misfolded protein regions? or reliability of kinetic and thermodynamic data (how much protein was in its native form?. As a consequence, the results of single experiments might not only become questionable, but the whole reliability of systems biology, built on these fundaments, would be weakened. The introduction of Minimal Information concerning purified proteins to add as metadata to the main body of a manuscript would render straightforward the assessment of their functional and structural qualities and, consequently, of results obtained using these proteins. Furthermore, accepted standards for protein annotation would simplify data comparison and exchange. This article has been envisaged as a proposal for aggregating scientists who share the opinion that the scientific community needs a platform for Minimum Information for Protein Functionality Evaluation (MIPFE.

  20. In silico determination of intracellular glycosylation and phosphorylation sites in human selectins: Implications for biological function

    DEFF Research Database (Denmark)

    Ahmad, I.; Hoessli, D.C.; Gupta, Ramneek

    2007-01-01

    Post-translational modifications provide the proteins with the possibility to perform functions in addition to those determined by their primary sequence. However, analysis of multifunctional protein structures in the environment of cells and body fluids is made especially difficult by the presence...... both modifications are likely to occur can also be predicted (YinYang sites), to suggest further functional versatility. Structural modifications of hydroxyl groups of P-, E-, and L-selectins have been predicted and possible functions resulting from such modifications are proposed. Functional changes...... of the three selectins are based on the assumption that transitory and reversible protein modifications by phosphate and O-GlcNAc cause specific conformational changes and generate binding sites for other proteins. The computer-assisted prediction of glycosylation and phosphorylation sites in selectins should...

  1. Expanding roles for GILT in immunity

    OpenAIRE

    West, Laura Ciaccia; Cresswell, Peter

    2012-01-01

    Gamma-interferon-inducible lysosomal thiol reductase (GILT), a thioredoxin-related oxidoreductase, functions in MHC class II-restricted antigen processing and MHC class I-restricted cross-presentation by reducing disulfide bonds of endocytosed proteins and facilitating their unfolding and optimal degradation. However, recent reports have greatly expanded our understanding of GILT’s function. Several studies of GILT and antigen processing have shown that the influence of GILT on the peptide re...

  2. A Tricky Trait: Applying the Fruits of the "Function Debate" in the Philosophy of Biology to the "Venom Debate" in the Science of Toxinology.

    Science.gov (United States)

    Jackson, Timothy N W; Fry, Bryan G

    2016-09-07

    The "function debate" in the philosophy of biology and the "venom debate" in the science of toxinology are conceptually related. Venom systems are complex multifunctional traits that have evolved independently numerous times throughout the animal kingdom. No single concept of function, amongst those popularly defended, appears adequate to describe these systems in all their evolutionary contexts and extant variations. As such, a pluralistic view of function, previously defended by some philosophers of biology, is most appropriate. Venom systems, like many other functional traits, exist in nature as points on a continuum and the boundaries between "venomous" and "non-venomous" species may not always be clearly defined. This paper includes a brief overview of the concept of function, followed by in-depth discussion of its application to venom systems. A sound understanding of function may aid in moving the venom debate forward. Similarly, consideration of a complex functional trait such as venom may be of interest to philosophers of biology.

  3. Functional Nanomaterials with Aggregation-Induced Emission Characteristics: Synthesis, Properties and Biological Applications

    Science.gov (United States)

    Kwok, Tsz Kin

    Fluorescent nanomaterials have great promise in bioanalysis and biotechnological applications because of their unique optical properties, high surface-to-volume ratio, and surface-modifiable quality. The development of fluorescent biosensors with high sensitivity, selectivity, and biocompatibility is of critical importance because it offers a direct visualization tool for the detection of biological macromolecules and the monitoring of biological events in living systems. Most of the conventional organic fluorophores, however, suffer from the self-quenching problem at high concentration or in the aggregated state. Such aggregation-cause quenching (ACQ) effect has greatly limited the scope of their bio-applications. Recently, our group discovered such a system, in which luminogen aggregation plays a constructive, instead of destructive, role in the light-emitting process. We have termed this abnormal phenomenon as "aggregation-induced emission" (AIE) and identified the restriction of intramolecular rotation as the main cause of the AIE effect. Attracted by the intriguing phenomenon and its fascinating perspectives, we have launched a new program directed towards the development of new AIE materials and exploration of their biological applications. In this work, a series of water-soluble AIE luminogens are designed and synthesized. Hydrophilic groups such as amino and sulfonate groups are incorporated into the AIE structures to impart them with good water solubility. Being practically non-emissive in water, these AIE luminogens are induced to emit intensely when bound to biomacromolecules, such as heparin, protamine and albumins, through hydrophobic and electrostatic interactions. Such light-up property enables the quantitation and visualization of biomacromolecules in aqueous solution and in electrophoretic gels. Incorporation of cleavable hydrophilic bioconjugates into AIE luminogens can enhance the specificity of the bioprobes. The bioprobes are nonluminscent in

  4. Functional biology and ecological role of krill in Northern marine ecosystems

    DEFF Research Database (Denmark)

    Agersted, Mette Dalgaard

    ) and by production of fast sinking carbon-rich faecal pellets. Hence, the large schools of krill greatly influence the pelagic food web and the flux of organic matter in the sea. However, knowledge of the distribution and feeding biology in krill from northern areas is scarce, although of importance to get a better...... understanding of the marine ecosystems and food webs. This thesis aimed to gain more knowledge of krill in northern hemisphere and to study their trophic position and grazing impact in a sub-Arctic fjord. The project investigated i) species and population composition of krill in the area of Godthåbsfjord, SW...... assumed to be the main grazers in marine ecosystems. This suggests that krill could be and are - in the case of Godthåbsfjord - important grazers that deserve more attention in future monitoring and research programs...

  5. Nitric oxide function in plant biology: a redox cue in deconvolution.

    Science.gov (United States)

    Yu, Manda; Lamattina, Lorenzo; Spoel, Steven H; Loake, Gary J

    2014-06-01

    Nitric oxide (NO), a gaseous, redox-active small molecule, is gradually becoming established as a central regulator of growth, development, immunity and environmental interactions in plants. A major route for the transfer of NO bioactivity is S-nitrosylation, the covalent attachment of an NO moiety to a protein cysteine thiol to form an S-nitrosothiol (SNO). This chemical transformation is rapidly emerging as a prototypic, redox-based post-translational modification integral to the life of plants. Here we review the myriad roles of NO and SNOs in plant biology and, where known, the molecular mechanisms underpining their activity. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  6. Development of Functional Fluorescent Molecular Probes for the Detection of Biological Substances

    Science.gov (United States)

    Suzuki, Yoshio; Yokoyama, Kenji

    2015-01-01

    This review is confined to sensors that use fluorescence to transmit biochemical information. Fluorescence is, by far, the most frequently exploited phenomenon for chemical sensors and biosensors. Parameters that define the application of such sensors include intensity, decay time, anisotropy, quenching efficiency, and luminescence energy transfer. To achieve selective (bio)molecular recognition based on these fluorescence phenomena, various fluorescent elements such as small organic molecules, enzymes, antibodies, and oligonucleotides have been designed and synthesized over the past decades. This review describes the immense variety of fluorescent probes that have been designed for the recognitions of ions, small and large molecules, and their biological applications in terms of intracellular fluorescent imaging techniques. PMID:26095660

  7. The biology and function of extracellular vesicles in nasopharyngeal carcinoma (Review).

    Science.gov (United States)

    You, Bo; Shan, Ying; Bao, Lili; Chen, Jing; Yang, Liu; Zhang, Qicheng; Zhang, Wei; Zhang, Zhenxin; Zhang, Jie; Shi, Si; You, Yiwen

    2018-01-01

    Extracellular vesicles are a heterogeneous group of membrane-enclosed vesicles, which play an important role in intercellular communication. Increasing number of studies have shown that tumor-derived extracellular vesicles might be involved in the transfer of oncogenic cargo (proteins, lipids, messenger RNA, microRNA, non-coding RNAs and DNA) through which cancer cells could shape the tumor microenvironment and influence tumor progression. Nasopharyngeal carcinoma-derived extracellular vesicles have also reported to facilitate tumor proliferation, metastasis and immune escape. Moreover, nasopharyngeal carcinoma-derived extracellular vesicles might serve as biomarkers for early diagnosis and therapeutic targets. The present review provides information on the biological and clinical significance of extracellular vesicles in tumors, especially in nasopharyngeal carcinoma.

  8. Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Demontis, Ditte; Castro Dias Cuyabano, Beatriz

    2016-01-01

    Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited...... power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from...... genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT...

  9. Role and Function of MicroRNAs in Extracellular Vesicles in Cardiovascular Biology

    Directory of Open Access Journals (Sweden)

    Philipp Pfeifer

    2015-01-01

    Full Text Available Intercellular communication mediated by extracellular vesicles is crucial for preserving vascular integrity and in the development of cardiovascular disease. Extracellular vesicles consist of apoptotic bodies, microvesicles, and exosomes that can be found in almost every fluid compartment of the body like blood, saliva, and urine. In the recent years, a lot of reports came up suggesting that major cardiovascular and metabolic pathologies like atherogenesis, heart failure, or diabetes are highly influenced by transfer of microRNAs via extracellular vesicles leading to altered protein expression and phenotypes of recipient cells. The following review will summarize the fast developing field of intercellular signaling in cardiovascular biology by microRNA-containing extracellular vesicles.

  10. Bank Directors’ Perceptions of Expanded Auditor's Reports

    DEFF Research Database (Denmark)

    Boolaky, Pran Krishansing; Quick, Reiner

    2016-01-01

    of expanded audit reports, namely information on the assurance level, materiality levels and key audit matters (KAM), on bank director perceptions of the quality of the financial statements, the audit and the audit report, as well as on their credit approval decisions. We conduct an experiment involving......Subsequent to the financial crisis, standard setters developed suggestions for enhancing the audit function, in order to increase financial stability. One related idea is to expand the audit report disclosed to the public, to ensure that it is fit for purpose. This study investigates the impact...... the materiality level or KAM. As a consequence, standard setters should carefully analyse the effect of additional information before making decisions on expanding the content of the audit report. Such expansions are not necessarily perceived as useful by stakeholders. © 2016 John Wiley & Sons Ltd...

  11. The Artful Universe Expanded

    Science.gov (United States)

    Barrow, John D.

    2005-07-01

    Our love of art, writes John Barrow, is the end product of millions of years of evolution. How we react to a beautiful painting or symphony draws upon instincts laid down long before humans existed. Now, in this enhanced edition of the highly popular The Artful Universe , Barrow further explores the close ties between our aesthetic appreciation and the basic nature of the Universe. Barrow argues that the laws of the Universe have imprinted themselves upon our thoughts and actions in subtle and unexpected ways. Why do we like certain types of art or music? What games and puzzles do we find challenging? Why do so many myths and legends have common elements? In this eclectic and entertaining survey, Barrow answers these questions and more as he explains how the landscape of the Universe has influenced the development of philosophy and mythology, and how millions of years of evolutionary history have fashioned our attraction to certain patterns of sound and color. Barrow casts the story of human creativity and thought in a fascinating light, considering such diverse topics as our instinct for language, the origins and uses of color in nature, why we divide time into intervals as we do, the sources of our appreciation of landscape painting, and whether computer-generated fractal art is really art. Drawing on a wide variety of examples, from the theological questions raised by St. Augustine and C.S. Lewis to the relationship between the pure math of Pythagoras and the music of the Beatles, The Artful Universe Expanded covers new ground and enters a wide-ranging debate about the meaning and significance of the links between art and science.

  12. Biological aspects and life table of Uroleucon ambrosiae (Thomas, 1878 as a function of temperature

    Directory of Open Access Journals (Sweden)

    Auad Alexander Machado

    2003-01-01

    Full Text Available The aphid Uroleucon ambrosiae (Thomas is considered a pest of hidroponically-grown lettuce, but basic and applied information on its control are scarce in Brazil. The aim of this study was to determine the effect of different temperatures on biological aspects and life history of U. ambrosiae (Thomas developing on hydroponic lettuce (Lactuca sativa L. crop. Newly emerged nymphs were placed on 4-cm discs of hydroponic lettuce, var. Verônica, which were maintained on 5-cm Petri dishes, at temperatures of 15, 20 and 25ºC and 14 h photophase, and inside a greenhouse, within micro-cages at room temperature. The duration of development in all nymphal stages varied inversely to temperature. Nymphs maintained at 20ºC and 25ºC, had similar development period. However, at fluctuating greenhouse temperatures (daily mean = 21ºC, different results were obtained, which was also true for the pre-reproductive, reproductive and post-reproductive periods. Daily and total fertilities at 20ºC were better in comparison to the other treatments. The highest mortality rate of aphids occurred under greenhouse conditions. The production of 1.28 nymphs per female per day, the time needed for the population to double in size (TD=2.77days, and the intrinsic rate of population increase (r m=0.25, were similar for in insects maintained at 20 and 25ºC. On the other hand, time interval between generations (T and the net reproductive rate (Ro were higher at 20ºC. In the greenhouse, even though T was similar to laboratory conditions at 20 and 25ºC, the R0, r m and l parameters were lower and TD was higher. Based on biological aspects, fertility and life expectancy tables, constant temperature of 20ºC is the most suitable for U. ambrosiae.

  13. MYC function and regulation in flies: how Drosophila has enlightened MYC cancer biology

    Directory of Open Access Journals (Sweden)

    Jue Er Amanda Lee

    2014-12-01

    Full Text Available Progress in our understanding of the complex signaling events driving human cancer would have been unimaginably slow without discoveries from Drosophila genetic studies. Significantly, many of the signaling pathways now synonymous with cancer biology were first identified as a result of elegant screens for genes fundamental to metazoan development. Indeed the name given to many core cancer-signaling cascades tells of their history as developmental patterning regulators in flies—e.g. Wingless (Wnt, Notch and Hippo. Moreover, astonishing insight has been gained into these complex signaling networks, and many other classic oncogenic signaling networks (e.g. EGFR/RAS/RAF/ERK, InR/PI3K/AKT/TOR, using sophisticated fly genetics. Of course if we are to understand how these signaling pathways drive cancer, we must determine the downstream program(s of gene expression activated to promote the cell and tissue over growth fundamental to cancer. Here we discuss one commonality between each of these pathways: they are all implicated as upstream activators of the highly conserved MYC oncogene and transcription factor. MYC can drive all aspects of cell growth and cell cycle progression during animal development. MYC is estimated to be dysregulated in over 50% of all cancers, underscoring the importance of elucidating the signals activating MYC. We also discuss the FUBP1/FIR/FUSE system, which acts as a ‘cruise control’ on the MYC promoter to control RNA Polymerase II pausing and, therefore, MYC transcription in response to the developmental signaling environment. Importantly, the striking conservation between humans and flies within these major axes of MYC regulation has made Drosophila an extremely valuable model organism for cancer research. We therefore discuss how Drosophila studies have helped determine the validity of signaling pathways regulating MYC in vivo using sophisticated genetics, and continue to provide novel insight into cancer biology.

  14. Discovery of a new method for potent drug development using power function of stoichiometry ofhomomeric biocomplexes or biological nanomotors

    Science.gov (United States)

    Pi, Fengmei; Vieweger, Mario; Zhao, Zhengyi; Wang, Shaoying; Guo, Peixuan

    2015-01-01

    Introduction Multidrug resistance and the appearance of incurable diseases inspire the quest for potent therapeutics. Areas Covered We review a new methodology in designing potent drugs by targeting multi-subunit homomeric biological motors, machines, or complexes with Z>1 and K=1, where Z is the stoichiometry of the target, and K is the number of drugged subunits required to block the function of the complex. The condition is similar to a series, electrical circuit of Christmas decorations; failure of one light bulb causes the entire lighting system to lose power. In most multisubunit, homomeric biological systems, a sequential coordination or cooperative action mechanism is utilized, thus K equals 1. Drug inhibition depends on the ratio of drugged to nondrugged complexes. When K=1, and Z>1, the inhibition effect follows a power law with respect to Z, leading to enhanced drug potency. The hypothesis that the potency of drug inhibition depends on the stoichiometry of the targeted biological complexes was recently quantified by Yang-Hui's Triangle (or binomial distribution), and proved using a highly sensitive in vitro phi29 viral DNA packaging system. Examples of targeting homomeric bio-complexes with high stoichiometry for potent drug discovery are discussed. Expert Opinion Biomotors with multiple subunits are widespread in viruses, bacteria, and cells, making this approach generally applicable in the development of inhibition drugs with high efficiency. PMID:26307193

  15. Ruminant Metabolic Systems Biology: Reconstruction and Integration of Transcriptome Dynamics Underlying Functional Responses of Tissues to Nutrition and Physiological Statea

    Science.gov (United States)

    Bionaz, Massimo; Loor, Juan J.

    2012-01-01

    High-throughput ‘omics’ data analysis via bioinformatics is one key component of the systems biology approach. The systems approach is particularly well-suited for the study of the interactions between nutrition and physiological state with tissue metabolism and functions during key life stages of organisms such as the transition from pregnancy to lactation in mammals, ie, the peripartal period. In modern dairy cows with an unprecedented genetic potential for milk synthesis, the nature of the physiologic and metabolic adaptations during the peripartal period is multifaceted and involves key tissues such as liver, adipose, and mammary. In order to understand such adaptation, we have reviewed several works performed in our and other labs. In addition, we have used a novel bioinformatics approach, Dynamic Impact Approach (DIA), in combination with partly previously published data to help interpret longitudinal biological adaptations of bovine liver, adipose, and mammary tissue to lactation using transcriptomics datasets. Use of DIA with transcriptomic data from those tissues during normal physiological adaptations and in animals fed different levels of energy prepartum allowed visualization and integration of most-impacted metabolic pathways around the time of parturition. The DIA is a suitable tool for applying the integrative systems biology approach. The ultimate goal is to visualize the complexity of the systems at study and uncover key molecular players involved in the tissue’s adaptations to physiological state or nutrition. PMID:22807626

  16. Mammalian synthetic biology for studying the cell.

    Science.gov (United States)

    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.

  17. Functional soil microbial diversity across Europe estimated by EEA, MicroResp and BIOLOG

    DEFF Research Database (Denmark)

    Winding, Anne; Rutgers, Michiel; Creamer, Rachel

    Soil microorganisms are abundant and essential for the bio-geochemical processes of soil, soil quality and soil ecosystem services. All this is dependent on the actual functions the microbial communities are performing in the soil. Measuring soil respiration has for many years been the basis...... of estimating soil microbial activity. However, today several techniques are in use for determining microbial functional diversity and assessing soil biodiversity: Methods based on CO2 development by the microbes such as substrate induced respiration (SIR) on specific substrates have lead to the development...... of MicroResp and Community Level Physiological Profile (CLPP), while soil enzymatic activity are being assayed by Extracellular Enzyme Activity (EEA) based on MUF-substrates. Here we compared and contrasted the three techniques of assessing soil microbial functional diversity in a European transect...

  18. PD-1 blockade restores impaired function of ex vivo expanded CD8+ T cells and enhances apoptosis in mismatch repair deficient EpCAM+PD-L1+ cancer cells

    Directory of Open Access Journals (Sweden)

    Kumar R

    2017-07-01

    Full Text Available Rajeev Kumar,1,2 Fang Yu,1 Yuan-Huan Zhen,3 Bo Li,2 Jun Wang,1 Yuan Yang,1,2 Hui-Xin Ge,4 Ping-Sheng Hu,1,2 Jin Xiu1,2 1Clinical Research Centre, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 2Cancer Immunology and Immunotherapy Centre, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 3Department of Colorectal Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 4Department of Surgery, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, People’s Republic of China Background: Adoptive T cell therapy has been proven to be a promising modality for the treatment of cancer patients in recent years. However, the increased expression of inhibitory receptors could negatively regulate the function and persistence of transferred T cells which mediates T cell anergy, exhaustion, and tumor regression. In this study, we investigated increased cytotoxic activity after the blockade of PD-1 for effective immunotherapy.Methods: The cytotoxic function of expanded CD8+ CTLs and interactions with tumor cells investigated after blocking of PD-1. Ex vivo expanded CD8+ CTLs were co-cultured with mismatch repair (MMR stable or deficient (high microsatellite instability [MSI-H] EpCAM+ tumor cells. The levels of IFN-γ and GrB were detected by enzyme-linked immunosorbent spot assay. Flow cytometry and confocal microscopy were used to assess CD107a mobilization, cytosolic uptake, and cell migration. Results: A dramatic increase in PD-1 expression on the surface of CD8+ CTLs during ex vivo expansion was observed. PD-1 level was downregulated by approximately 40% after incubation of the CD8+ CTLs with monoclonal antibody which enhanced the secretion of IFN-γ, GrB, and CD107a. Additionally, PD-1 blockade enhanced cell migration and cytosolic exchange between CD8+ CTLs and MMR deficient (MSI-H EpCAM+PD-L1+ tumor

  19. Advances in deep-sea biology: biodiversity, ecosystem functioning and conservation. An introduction and overview

    Science.gov (United States)

    Cunha, Marina R.; Hilário, Ana; Santos, Ricardo S.

    2017-03-01

    Once considered as monotonous and devoid of life, the deep sea was revealed during the last century as an environment with a plethora of life forms and extremely high species richness (Rex and Etter, 2010). Underwater vehicle developments allowed direct observations of the deep, disclosing unique habitats and diverse seascapes, and other technological advances enabled manipulative experimentation and unprecedented prospects to pursue novel research topics (Levin and Sibuet, 2012; Danovaro et al., 2014). Alongside, the growing human population greatly increased the pressure on deep-sea ecosystems and the services they provide (Ramirez-Llodra et al., 2011; Thurber et al., 2014; Levin et al., 2016). Societal changes further intensified worldwide competition for natural resources, extending the present footprint of impacts over most of the global ocean (Halpern et al., 2008). In this socio-economic context, and in tandem with cutting edge technological advances and an unclear legal framework to regulate access to natural resources (Boyes and Elliott, 2014), the deep sea has emerged as a new opportunity for industrial exploitation and novel economic activities. The expanding use of the deep sea prompted a rapid reply from deep-sea scientists that recommended ;a move from a frontier mentality of exploitation and single-sector management to a precautionary system that balances use of living marine resources, energy, and minerals from the deep ocean with maintenance of a productive and healthy marine environment, while improving knowledge and collaboration; and proposed ;three directions to advance deep-ocean stewardship: i) protection and mitigation, ii) research, and iii) collaborative governance; (Mengerink et al., 2014). The European Marine Board position paper 22 (Rogers et al., 2015) further examined the key societal and environmental drivers confronting the deep sea and the role of deep-sea research to deliver future knowledge needs for science and society; a clear

  20. The Paradox of the Missing Biological Function in Understanding: Implications for Moral and General Education

    Science.gov (United States)

    Iran-Nejad, Asghar

    2013-01-01

    This essay argues that the endemic moral crisis and the crisis of confidence in education are related; and both are a function, in part, of a paradoxical divide between two types of human understanding: psychological and biofunctional. In the psychological realm, people cause understanding using the psychological theories they know.…

  1. Assessment of the biological control capability of Hippodamia variegata (Col.: Coccinellidae) using functional response experiments

    DEFF Research Database (Denmark)

    Madadi, Hossein; Parizi, Emad Mohajeri; Allahyari, Hossein

    2011-01-01

    Lady beetles are among the most successful predators of aphids in different environments. The functional responses of different life stages of Hippodamia variegata (Goeze) towards cotton aphidswere examined in two different set-ups, a two-dimensional Petri dish set-up with detached leaves and a t...

  2. The fine-grained metaphysics of artifactual and biological functional kinds

    NARCIS (Netherlands)

    Carrara, M.; Vermaas, P.E.

    2008-01-01

    In this paper we consider the emerging position in metaphysics that artifact functions characterize real kinds of artifacts. We analyze how it can circumvent an objection by David Wiggins (Sameness and substance renewed, 2001, 87) and then argue that this position, in comparison to expert judgments,

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  5. Systems biology in animal sciences

    NARCIS (Netherlands)

    Woelders, H.; Pas, te M.F.W.; Bannink, A.; Veerkamp, R.F.; Smits, M.A.

    2011-01-01

    Systems biology is a rapidly expanding field of research and is applied in a number of biological disciplines. In animal sciences, omics approaches are increasingly used, yielding vast amounts of data, but systems biology approaches to extract understanding from these data of biological processes

  6. Biological function analysis of monoclonal antibodies against human granulins in vitro using U251 cells as a model.

    Science.gov (United States)

    Li, Yanqing; Li, Ya; Ye, Mingfu; Wang, Dongyang; Zhao, Junli; Sun, Xiaohong; Mao, Qinwen; Xia, Haibin

    2017-02-01

    Progranulin (PGRN), a highly glycosylated, secreted 593 amino acid precursor protein, is a multifunctional molecule that is critical for early embryogenesis, wound repair, inflammatory and tumorigenesis. PGRN can be proteolytically cleaved into seven cysteine-rich granulin (Grn) peptides: G, F, B, A, C, D and E. Both PGRN and its constituent Grn peptides have been implicated in a wide variety of biological activities. However, their functions are far from clear, and the lack of granulin domain-specific antibodies has hindered the progress of the functional study of PGRN and Grns. Monoclonal antibodies against GrnB, GrnA, GrnC and GrnF have been previously developed by our laboratory. In this study, we generated monoclonal antibodies (MAbs) against GrnD, GrnG and GrnE by using recombinant proteins HSA-GrnG, HSA-GrnD and HSA-GrnE as immunogens, and characterized them by indirect ELISA, Western blot and immunocytochemistry. Furthermore, the neutralizing activities of the MAbs against seven Grns were tested in vitro using the U251 cell line. This full antibody panel of MAbs against seven Grns will be a valuable tool for elucidating the biological roles of PGRN and Grns in different physiopathological processes, which will further promote the development of PGRN-based clinical diagnosis and therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Reproductive biology and functional response of Dineulophus phtorimaeae, a natural enemy of the tomato moth, Tuta absoluta.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  9. Using synthetic biology to distinguish and overcome regulatory and functional barriers related to nitrogen fixation.

    Directory of Open Access Journals (Sweden)

    Xia Wang

    Full Text Available Biological nitrogen fixation is a complex process requiring multiple genes working in concert. To date, the Klebsiella pneumoniae nif gene cluster, divided into seven operons, is one of the most studied systems. Its nitrogen fixation capacity is subject to complex cascade regulation and physiological limitations. In this report, the entire K. pneumoniae nif gene cluster was reassembled as operon-based BioBrick parts in Escherichia coli. It provided ~100% activity of native K. pneumoniae system. Based on the expression levels of these BioBrick parts, a T7 RNA polymerase-LacI expression system was used to replace the σ(54-dependent promoters located upstream of nif operons. Expression patterns of nif operons were critical for the maximum activity of the recombinant system. By mimicking these expression levels with variable-strength T7-dependent promoters, ~42% of the nitrogenase activity of the σ(54-dependent nif system was achieved in E. coli. When the newly constructed T7-dependent nif system was challenged with different genetic and physiological conditions, it bypassed the original complex regulatory circuits, with minor physiological limitations. Therefore, we have successfully replaced the nif regulatory elements with a simple expression system that may provide the first step for further research of introducing nif genes into eukaryotic organelles, which has considerable potentials in agro-biotechnology.

  10. Exploring the Shift in Structure and Function of Microbial Communities Performing Biological Phosphorus Removal.

    Science.gov (United States)

    Mao, Yanping; Wang, Zhiping; Li, Liguan; Jiang, Xiaotao; Zhang, Xuxiang; Ren, Hongqiang; Zhang, Tong

    2016-01-01

    A sequencing batch reactor fed mainly by acetate was operated to perform enhanced biological phosphorus removal (EBPR). A short-term pH shock from 7.0 to 6.0 led to a complete loss of phosphate-removing capability and a drastic change of microbial communities. 16S rRNA gene pyrosequencing showed that large proportions of glycogen accumulating organisms (GAOs) (accounted for 16% of bacteria) bloomed, including Candidatus Competibacter phosphatis and Defluviicoccus-related tetrad-forming organism, causing deteriorated EBPR performance. The EBPR performance recovered with time and the dominant Candidatus Accumulibacter (Accumulibacter) clades shifted from Clade IIC to IIA while GAOs populations shrank significantly. The Accumulibacter population variation provided a good opportunity for genome binning using a bi-dimensional coverage method, and a genome of Accumulibacter Clade IIC was well retrieved with over 90% completeness. Comparative genomic analysis demonstrated that Accumulibacter clades had different abilities in nitrogen metabolism and carbon fixation, which shed light on enriching different Accumulibacter populations selectively.

  11. Exploring the Shift in Structure and Function of Microbial Communities Performing Biological Phosphorus Removal.

    Directory of Open Access Journals (Sweden)

    Yanping Mao

    Full Text Available A sequencing batch reactor fed mainly by acetate was operated to perform enhanced biological phosphorus removal (EBPR. A short-term pH shock from 7.0 to 6.0 led to a complete loss of phosphate-removing capability and a drastic change of microbial communities. 16S rRNA gene pyrosequencing showed that large proportions of glycogen accumulating organisms (GAOs (accounted for 16% of bacteria bloomed, including Candidatus Competibacter phosphatis and Defluviicoccus-related tetrad-forming organism, causing deteriorated EBPR performance. The EBPR performance recovered with time and the dominant Candidatus Accumulibacter (Accumulibacter clades shifted from Clade IIC to IIA while GAOs populations shrank significantly. The Accumulibacter population variation provided a good opportunity for genome binning using a bi-dimensional coverage method, and a genome of Accumulibacter Clade IIC was well retrieved with over 90% completeness. Comparative genomic analysis demonstrated that Accumulibacter clades had different abilities in nitrogen metabolism and carbon fixation, which shed light on enriching different Accumulibacter populations selectively.

  12. Using synthetic biology to distinguish and overcome regulatory and functional barriers related to nitrogen fixation.

    Science.gov (United States)

    Wang, Xia; Yang, Jian-Guo; Chen, Li; Wang, Ji-Long; Cheng, Qi; Dixon, Ray; Wang, Yi-Ping

    2013-01-01

    Biological nitrogen fixation is a complex process requiring multiple genes working in concert. To date, the Klebsiella pneumoniae nif gene cluster, divided into seven operons, is one of the most studied systems. Its nitrogen fixation capacity is subject to complex cascade regulation and physiological limitations. In this report, the entire K. pneumoniae nif gene cluster was reassembled as operon-based BioBrick parts in Escherichia coli. It provided ~100% activity of native K. pneumoniae system. Based on the expression levels of these BioBrick parts, a T7 RNA polymerase-LacI expression system was used to replace the σ(54)-dependent promoters located upstream of nif operons. Expression patterns of nif operons were critical for the maximum activity of the recombinant system. By mimicking these expression levels with variable-strength T7-dependent promoters, ~42% of the nitrogenase activity of the σ(54)-dependent nif system was achieved in E. coli. When the newly constructed T7-dependent nif system was challenged with different genetic and physiological conditions, it bypassed the original complex regulatory circuits, with minor physiological limitations. Therefore, we have successfully replaced the nif regulatory elements with a simple expression system that may provide the first step for further research of introducing nif genes into eukaryotic organelles, which has considerable potentials in agro-biotechnology.

  13. Ecology and functional roles of biological soil crusts in semi-arid ecosystems of Spain

    Science.gov (United States)

    Maestre, Fernando T.; Bowker, Matthew A.; Cantón, Yolanda; Castillo-Monroy, Andrea P.; Cortina, Jordi; Escolar, Cristina; Escudero, Adrián; Lázaro, Roberto; Martínez, Isabel

    2015-01-01

    Biological soil crusts (BSCs), composed of lichens, cyanobacteria, mosses, liverworts and microorganisms, are key biotic components of arid and semi-arid ecosystems worldwide. Despite they are widespread in Spain, these organisms have been historically understudied in this country. This trend is beginning to change as a recent wave of research has been identifying BSCs as a model ecological system. Many studies and research projects carried out in Spain have explored the role of BSCs on water, carbon and nitrogen fluxes, the interactions between BSCs and vascular plants, their dynamics after disturbances, and their response to global change, among other topics. In this article we review the growing body of research on BSCs available from semi-arid areas of Spain, highlighting its importance for increasing our knowledge on this group of organisms. We also discuss how it is breaking new ground in emerging research areas on the ecology of BSCs, and how it can be use to guide management and restoration efforts. Finally, we provide directions for future research on the ecology of BSCs in Spain and abroad. PMID:25908884

  14. Functionalization of lactose as a biological carrier for bovine serum albumin by electrospraying.

    Science.gov (United States)

    Tavares Cardoso, M A; Talebi, M; Soares, P A M H; Yurteri, C U; van Ommen, J R

    2011-07-29

    Electrohydrodynamic atomization (EHDA) is an attractive technique to make new types of composite particles for pharmaceutical use. The aim of this work is to prove that EHDA can be successfully used to attach nano/micro-particles of protein to lactose, the commonly used excipient for pulmonary delivery, keeping all the biological properties of the protein after dissolution of the complex. Bovine serum albumin (BSA) was used as a model protein. The atomization of BSA was tested with two different solvents, dimethyl sulfoxide (DMSO) and ethanol. The process using DMSO resulted in the formation of a thin layer of protein while the tests using ethanol resulted in the formation of spherical particles with mean diameters around 700 nm. Ethanol as solvent was also used to produce a composite formed by BSA adsorbed at the surface of lactose by electrostatic forces. No denaturation or significant conformational changes of the protein were observed, although an increase in the exposition of the lactose to the jet of the solution decreases the reproducibility of the method. Due to the absence of denaturation in the model protein, this new approach can be tested for the production of new formulations for dry powders for drug delivery systems. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y.; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H.; Johnson, Andrew D.; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F.; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B.; Nolte, Ilja M.; van der Most, Peter J.; Wright, Alan F.; Shuldiner, Alan R.; Morrison, Alanna C.; Hofman, Albert; Smith, Albert V.; Dreisbach, Albert W.; Franke, Andre; Uitterlinden, Andre G.; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I.; Ponte, Belen; Oostra, Ben A.; Paulweber, Bernhard; Krämer, Bernhard K.; Mitchell, Braxton D.; Buckley, Brendan M.; Peralta, Carmen A.; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N.; Shaffer, Christian M.; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M.; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S.; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J.; Holliday, Elizabeth G.; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P.; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B.; Navis, Gerjan J.; Curhan, Gary C.; Ehret, George B.; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W.; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K.; Kramer, Holly; Lin, Honghuang; Leach, I. Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M.; Kolcic, Ivana; Persico, Ivana; Jukema, J. Wouter; Wilson, James F.; Felix, Janine F.; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M.; Gaspoz, Jean-Michel; Smith, Jennifer A.; Faul, Jessica D.; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N.; Attia, John; Whitfield, John B.; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C.; Karjalainen, Juha; Fernandes, Jyotika K.; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L.; Lohman, Kurt; Portas, Laura; Launer, Lenore J.; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M.; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E.; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C.; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A.; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K.; Sale, Michele M.; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G.; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H.; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B.; Ridker, Paul M.; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H.; Abecasis, Goncalo R.; Adair, Linda S.; Alexander, Myriam; Altshuler, David; Amin, Najaf; Arking, Dan E.; Arora, Pankaj; Aulchenko, Yurii; Bakker, Stephan J. L.; Bandinelli, Stefania; Barroso, Ines; Beckmann, Jacques S.; Beilby, John P.; Bergman, Richard N.; Bergmann, Sven; Bis, Joshua C.; Boehnke, Michael; Bonnycastle, Lori L.; Bornstein, Stefan R.; Bots, Michiel L.; Bragg-Gresham, Jennifer L.; Brand, Stefan-Martin; Brand, Eva; Braund, Peter S.; Brown, Morris J.; Burton, Paul R.; Casas, Juan P.; Caulfield, Mark J.; Chakravarti, Aravinda; Chambers, John C.; Chandak, Giriraj R.; Chang, Yen-Pei C.; Charchar, Fadi J.; Chaturvedi, Nish; Shin Cho, Yoon; Clarke, Robert; Collins, Francis S.; Collins, Rory; Connell, John M.; Cooper, Jackie A.; Cooper, Matthew N.; Cooper, Richard S.; Corsi, Anna Maria; Dörr, Marcus; Dahgam, Santosh; Danesh, John; Smith, George Davey; Day, Ian N. M.; Deloukas, Panos; Denniff, Matthew; Dominiczak, Anna F.; Dong, Yanbin; Doumatey, Ayo; Elliott, Paul; Elosua, Roberto; Erdmann, Jeanette; Eyheramendy, Susana; Farrall, Martin; Fava, Cristiano; Forrester, Terrence; Fowkes, F. Gerald R.; Fox, Ervin R.; Frayling, Timothy M.; Galan, Pilar; Ganesh, Santhi K.; Garcia, Melissa; Gaunt, Tom R.; Glazer, Nicole L.; Go, Min Jin; Goel, Anuj; Grässler, Jürgen; Grobbee, Diederick E.; Groop, Leif; Guarrera, Simonetta; Guo, Xiuqing; Hadley, David; Hamsten, Anders; Han, Bok-Ghee; Hardy, Rebecca; Hartikainen, Anna-Liisa; Heath, Simon; Heckbert, Susan R.; Hedblad, Bo; Hercberg, Serge; Hernandez, Dena; Hicks, Andrew A.; Hilton, Gina; Hingorani, Aroon D.; Bolton, Judith A Hoffman; Hopewell, Jemma C.; Howard, Philip; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Ikram, M. Arfan; Islam, Muhammad; Iwai, Naoharu; Jarvelin, Marjo-Riitta; Jackson, Anne U.; Jafar, Tazeen H.; Janipalli, Charles S.; Johnson, Toby; Kathiresan, Sekar; Khaw, Kay-Tee; Kim, Hyung-Lae; Kinra, Sanjay; Kita, Yoshikuni; Kivimaki, Mika; Kooner, Jaspal S.; Kumar, M. J. Kranthi; Kuh, Diana; Kulkarni, Smita R.; Kumari, Meena; Kuusisto, Johanna; Kuznetsova, Tatiana; Laakso, Markku; Laan, Maris; Laitinen, Jaana; Lakatta, Edward G.; Langefeld, Carl D.; Larson, Martin G.; Lathrop, Mark; Lawlor, Debbie A.; Lawrence, Robert W.; Lee, Jong-Young; Lee, Nanette R.; Levy, Daniel; Li, Yali; Longstreth, Will T.; Luan, Jian'an; Lucas, Gavin; Ludwig, Barbara; Mangino, Massimo; Mani, K. Radha; Marmot, Michael G.; Mattace-Raso, Francesco U. S.; Matullo, Giuseppe; McArdle, Wendy L.; McKenzie, Colin A.; Meitinger, Thomas; Melander, Olle; Meneton, Pierre; Meschia, James F.; Miki, Tetsuro; Milaneschi, Yuri; Mohlke, Karen L.; Mooser, Vincent; Morken, Mario A.; Morris, Richard W.; Mosley, Thomas H.; Najjar, Samer; Narisu, Narisu; Newton-Cheh, Christopher; Nguyen, Khanh-Dung Hoang; Nilsson, Peter; Nyberg, Fredrik; O'Donnell, Christopher J.; Ogihara, Toshio; Ohkubo, Takayoshi; Okamura, Tomonori; Ong, RickTwee-Hee; Ongen, Halit; Onland-Moret, N. Charlotte; O'Reilly, Paul F.; Org, Elin; Orru, Marco; Palmas, Walter; Palmen, Jutta; Palmer, Lyle J.; Palmer, Nicholette D.; Parker, Alex N.; Peden, John F.; Peltonen, Leena; Perola, Markus; Pihur, Vasyl; Platou, Carl G. P.; Plump, Andrew; Prabhakaran, Dorairajan; Psaty, Bruce M.; Raffel, Leslie J.; Rao, Dabeeru C.; Rasheed, Asif; Ricceri, Fulvio; Rice, Kenneth M.; Rosengren, Annika; Rotter, Jerome I.; Rudock, Megan E.; Sõber, Siim; Salako, Tunde; Saleheen, Danish; Salomaa, Veikko; Samani, Nilesh J.; Schwartz, Steven M.; Schwarz, Peter E. H.; Scott, Laura J.; Scott, James; Scuteri, Angelo; Sehmi, Joban S.; Seielstad, Mark; Seshadri, Sudha; Sharma, Pankaj; Shaw-Hawkins, Sue; Shi, Gang; Shrine, Nick R. G.; Sijbrands, Eric J. G.; Sim, Xueling; Singleton, Andrew; Sjögren, Marketa; Smith, Nicholas L.; Artigas, Maria Soler; Spector, Tim D.; Staessen, Jan A.; Stancakova, Alena; Steinle, Nanette I.; Strachan, David P.; Stringham, Heather M.; Sun, Yan V.; Swift, Amy J.; Tabara, Yasuharu; Tai, E-Shyong; Talmud, Philippa J.; Taylor, Andrew; Terzic, Janos; Thelle, Dag S.; Tobin, Martin D.; Tomaszewski, Maciej; Tripathy, Vikal; Tuomilehto, Jaakko; Tzoulaki, Ioanna; Uda, Manuela; Ueshima, Hirotsugu; Uiterwaal, Cuno S. P. M.; Umemura, Satoshi; van der Harst, Pim; van der Schouw, Yvonne T.; van Gilst, Wiek H.; Vartiainen, Erkki; Vasan, Ramachandran S.; Veldre, Gudrun; Verwoert, Germaine C.; Viigimaa, Margus; Vinay, D. G.; Vineis, Paolo; Voight, Benjamin F.; Vollenweider, Peter; Wagenknecht, Lynne E.; Wain, Louise V.; Wang, Xiaoling; Wang, Thomas J.; Wareham, Nicholas J.; Watkins, Hugh; Weder, Alan B.; Whincup, Peter H.; Wiggins, Kerri L.; Witteman, Jacqueline C. M.; Wong, Andrew; Wu, Ying; Yajnik, Chittaranjan S.; Yao, Jie; Young, J. H.; Zelenika, Diana; Zhai, Guangju; Zhang, Weihua; Zhang, Feng; Zhao, Jing Hua; Zhu, Haidong; Zhu, Xiaofeng; Zitting, Paavo; Zukowska-Szczechowska, Ewa; Okada, Yukinori; Wu, Jer-Yuarn; Gu, Dongfeng; Takeuchi, Fumihiko; Takahashi, Atsushi; Maeda, Shiro; Tsunoda, Tatsuhiko; Chen, Peng; Lim, Su-Chi; Wong, Tien-Yin; Liu, Jianjun; Young, Terri L.; Aung, Tin; Teo, Yik-Ying; Kim, Young Jin; Kang, Daehee; Chen, Chien-Hsiun; Tsai, Fuu-Jen; Chang, Li-Ching; Fann, S. -J. Cathy; Mei, Hao; Hixson, James E.; Chen, Shufeng; Katsuya, Tomohiro; Isono, Masato; Albrecht, Eva; Yamamoto, Kazuhiko; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki; Kato, Norihiro; He, Jiang; Chen, Yuan-Tsong; Tanaka, Toshihiro; Reilly, Muredach P; Schunkert, Heribert; Assimes, Themistocles L.; Hall, Alistair; Hengstenberg, Christian; König, Inke R.; Laaksonen, Reijo; McPherson, Ruth; Thompson, John R.; Thorsteinsdottir, Unnur; Ziegler, Andreas; Absher, Devin; Chen, Li; Cupples13, L. Adrienne; Halperin, Eran; Li, Mingyao; Musunuru, Kiran; Preuss, Michael; Schillert, Arne; Thorleifsson, Gudmar; Wells, George A.; Holm, Hilma; Roberts, Robert; Stewart, Alexandre F. R.; Fortmann, Stephen; Go, Alan; Hlatky, Mark; Iribarren, Carlos; Knowles, Joshua; Myers, Richard; Quertermous, Thomas; Sidney, Steven; Risch, Neil; Tang, Hua; Blankenberg, Stefan; Schnabel, Renate; Sinning, Christoph; Lackner, Karl J.; Tiret, Laurence; Nicaud, Viviane; Cambien, Francois; Bickel, Christoph; Rupprecht, Hans J.; Perret, Claire; Proust, Carole; Münzel, Thomas F.; Barbalic, Maja; Chen, Ida Yii-Der; Demissie-Banjaw, Serkalem; Folsom, Aaron; Lumley, Thomas; Marciante, Kristin; Taylor, Kent D.; Volcik, Kelly; Gretarsdottir, Solveig; Gulcher, Jeffrey R.; Kong, Augustine; Stefansson, Kari; Thorgeirsson, Gudmundur; Andersen, Karl; Fischer, Marcus; Grosshennig, Anika; Linsel-Nitschke, Patrick; Stark, Klaus; Schreiber, Stefan; Aherrahrou, Zouhair; Bruse, Petra; Doering, Angela; Klopp, Norman; Diemert, Patrick; Loley, Christina; Medack, Anja; Nahrstedt, Janja; Peters, Annette; Wagner, Arnika K.; Willenborg, Christina; Böhm, Bernhard O.; Dobnig, Harald; Grammer, Tanja B.; Hoffmann, Michael M.; Meinitzer, Andreas; Winkelmann, Bernhard R.; Pilz, Stefan; Renner, Wilfried; Scharnagl, Hubert; Stojakovic, Tatjana; Tomaschitz, Andreas; Winkler, Karl; Guiducci, Candace; Burtt, Noel; Gabriel, Stacey B.; Dandona, Sonny; Jarinova, Olga; Qu, Liming; Wilensky, Robert; Matthai, William; Hakonarson, Hakon H.; Devaney, Joe; Burnett, Mary Susan; Pichard, Augusto D.; Kent, Kenneth M.; Satler, Lowell; Lindsay, Joseph M.; Waksman, Ron; Knouff, Christopher W.; Waterworth, Dawn M.; Walker, Max C.; Epstein, Stephen E.; Rader, Daniel J.; Nelson, Christopher P.; Wright, Benjamin J.; Balmforth, Anthony J.; Ball, Stephen G.; Loehr, Laura R.; Rosamond, Wayne D.; Benjamin, Emelia; Haritunians, Talin; Couper, David; Murabito, Joanne; Wang, Ying A.; Stricker, Bruno H.; Chang, Patricia P.; Willerson, James T.; Felix, Stephan B.; Watzinger, Norbert; Aragam, Jayashri; Zweiker, Robert; Lind, Lars; Rodeheffer, Richard J.; Greiser, Karin Halina; Deckers, Jaap W.; Stritzke, Jan; Ingelsson, Erik; Kullo, Iftikhar; Haerting, Johannes; Reffelmann, Thorsten; Redfield, Margaret M.; Werdan, Karl; Mitchell, Gary F.; Arnett, Donna K.; Gottdiener, John S.; Blettner, Maria; Friedrich, Nele; Kovacs, Peter; Wild, Philipp S.; Froguel, Philippe; Rettig, Rainer; Mägi, Reedik; Biffar, Reiner; Schmidt, Reinhold; Middelberg, Rita P. S.; Carroll, Robert J.; Penninx, Brenda W.; Scott, Rodney J.; Katz, Ronit; Sedaghat, Sanaz; Wild, Sarah H.; Kardia, Sharon L. R.; Ulivi, Sheila; Hwang, Shih-Jen; Enroth, Stefan; Kloiber, Stefan; Trompet, Stella; Stengel, Benedicte; Hancock, Stephen J.; Turner, Stephen T.; Rosas, Sylvia E.; Stracke, Sylvia; Harris, Tamara B.; Zeller, Tanja; Zemunik, Tatijana; Lehtimäki, Terho; Illig, Thomas; Aspelund, Thor; Nikopensius, Tiit; Esko, Tonu; Tanaka, Toshiko; Gyllensten, Ulf; Völker, Uwe; Emilsson, Valur; Vitart, Veronique; Aalto, Ville; Gudnason, Vilmundur; Chouraki, Vincent; Chen, Wei-Min; Igl, Wilmar; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Loos, Ruth J. F.; Liu, Yongmei; Snieder, Harold; Pramstaller, Peter P.; Parsa, Afshin; O'Connell, Jeffrey R.; Susztak, Katalin; Hamet, Pavel; Tremblay, Johanne; de Boer, Ian H.; Böger, Carsten A.; Goessling, Wolfram; Chasman, Daniel I.; Köttgen, Anna; Kao, W. H. Linda; Fox, Caroline S.

    2016-01-01

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

  16. The EBI Search engine: providing search and retrieval functionality for biological data from EMBL-EBI.

    Science.gov (United States)

    Squizzato, Silvano; Park, Young Mi; Buso, Nicola; Gur, Tamer; Cowley, Andrew; Li, Weizhong; Uludag, Mahmut; Pundir, Sangya; Cham, Jennifer A; McWilliam, Hamish; Lopez, Rodrigo

    2015-07-01

    The European Bioinformatics Institute (EMBL-EBI-https://www.ebi.ac.uk) provides free and unrestricted access to data across all major areas of biology and biomedicine. Searching and extracting knowledge across these domains requires a fast and scalable solution that addresses the requirements of domain experts as well as casual users. We present the EBI Search engine, referred to here as 'EBI Search', an easy-to-use fast text search and indexing system with powerful data navigation and retrieval capabilities. API integration provides access to analytical tools, allowing users to further investigate the results of their search. The interconnectivity that exists between data resources at EMBL-EBI provides easy, quick and precise navigation and a better understanding of the relationship between different data types including sequences, genes, gene products, proteins, protein domains, protein families, enzymes and macromolecular structures, together with relevant life science literature. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Biological and functional diversity of bird communities in natural and human modified habitats in Northern Flank of Knuckles Mountain Forest Range, Sri Lanka

    OpenAIRE

    KALYA SUBASINGHE; AMILA P. SUMANAPALA

    2014-01-01

    Subasinghe K, Sumanapala AP. 2014. Biological and functional diversity of bird communities in natural and human modified habitats in Northern Flank of Knuckles Mountain Forest Range, Sri Lanka. Biodiversitas 15: 200-205. The Knuckles Mountain Forest Range (KMFR) has a complex mosaic of natural and human modified habitats and the contribution of these habitats to the biological and functional diversities has not been deeply studied. Present study investigated both of these diversities in five ...

  18. The biology, function and clinical implications of exosomes in lung cancer.

    Science.gov (United States)

    Zhou, Li; Lv, Tangfeng; Zhang, Qun; Zhu, Qingqing; Zhan, Ping; Zhu, Suhua; Zhang, Jianya; Song, Yong

    2017-10-28

    Exosomes are 30-100 nm small membrane vesicles of endocytic origin that are secreted by all types of cells, and can also be found in various body fluids. Increasing evidence implicates that exosomes confer stability and can deliver their cargos such as proteins and nucleic acids to specific cell types, which subsequently serve as important messengers and carriers in lung carcinogenesis. Here, we describe the biogenesis and components of exosomes mainly in lung cancer, we summarize their function in lung carcinogenesis (epithelial mesenchymal transition, oncogenic cell transformation, angiogenesis, metastasis and immune response in tumor microenvironment), and importantly we focus on the clinical potential of exosomes as biomarkers and therapeutics in lung cancer. In addition, we also discuss current challenges that might impede the clinical use of exosomes. Further studies on the functional roles of exosomes in lung cancer requires thorough research. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Bacterial-plant-interactions: approaches to unravel the biological function of bacterial volatiles in the rhizosphere

    Directory of Open Access Journals (Sweden)

    Marco eKai

    2016-02-01

    Full Text Available Rhizobacteria produce an enormous amount of volatile compounds, however, the function of these metabolites is scarcely understood. Investigations evaluating influences on plants performed in various laboratories using individually developed experimental setups revealed different and often contradictory results, e.g. ranging from a significant plant growth promotion to a dramatic suppression of plant development. In addition to these discrepancies, these test systems neglected properties and complexity of the rhizosphere. Therefore, to pursue further investigations of the role of bacterial volatiles in this underground habitat, the applied methods have to simulate its natural characteristics as much as possible. In this review, we will describe and discuss pros and cons of currently used bioassays, give insights into rhizosphere characteristics, and suggest improvements for test systems that would consider in natura conditions and would allow gaining further knowledge of the potential function and significance of rhizobacterial volatiles in plant life.

  20. Intersection of transfer cells with phloem biology – broad evolutionary trends, function and induction

    Directory of Open Access Journals (Sweden)

    Felicity eAndriunas

    2013-07-01

    Full Text Available Transfer cells (TCs are ubiquitous throughout the plant kingdom. Their unique ingrowth wall labyrinths, supporting a plasma membrane enriched in transporter proteins, provides these cells with an enhanced membrane transport capacity for resources. In certain plant species, TCs have been shown to function to facilitate phloem loading and/or unloading at cellular sites of intense resource exchange between symplasmic/apoplasmic compartments. Within the phloem, the key cellular locations of TCs are leaf minor veins of collection phloem and stem nodes of transport phloem. In these locations, companion and phloem parenchyma cells trans-differentiate to a TC morphology consistent with facilitating loading and re-distribution of resources respectively. At a species level, occurrence of TCs is significantly higher in transport than in collection phloem. TCs are absent from release phloem but occur within post-sieve element unloading pathways and particularly at interfaces between generations of developing Angiosperm seeds. Experimental accessibility of seed TCs has provided opportunities to investigate their inductive signaling, regulation of ingrowth wall formation and membrane transport function. This review uses this information base to explore current knowledge of phloem transport function and inductive signaling for phloem-associated TCs. The functional role of collection phloem and seed TCs is supported by definitive evidence, but no such information is available for stem node TCs that present an almost intractable experimental challenge. There is an emerging understanding of inductive signals and signaling pathways responsible for initiating trans-differentiation to a TC morphology in developing seeds. However, scant information is available to comment on a potential role for inductive signals that induce seed TCs, in regulating induction of phloem-associated TCs. Biotic phloem invaders have been used as a model to speculate on involvement of

  1. RNA-Mediated Silencing in Algae: Biological Roles and Tools for Analysis of Gene Function

    OpenAIRE

    Cerutti, Heriberto; Ma, Xinrong; Msanne, Joseph; Repas, Timothy

    2011-01-01

    Algae are a large group of aquatic, typically photosynthetic, eukaryotes that include species from very diverse phylogenetic lineages, from those similar to land plants to those related to protist parasites. The recent sequencing of several algal genomes has provided insights into the great complexity of these organisms. Genomic information has also emphasized our lack of knowledge of the functions of many predicted genes, as well as the gene regulatory mechanisms in algae. Core components of...

  2. The biological mechanisms and behavioral functions of opsin-based light detection by the skin

    Directory of Open Access Journals (Sweden)

    Jennifer L Kelley

    2016-08-01

    Full Text Available Light detection not only forms the basis of vision (via visual retinal photoreceptors, but can also occur in other parts of the body, including many non-rod/non-cone ocular cells, the pineal complex, the deep brain, and the skin. Indeed, many of the photopigments (an opsin linked to a light-sensitive 11-cis retinal chromophore that mediate color vision in the eyes of vertebrates are also present in the skin of animals such as reptiles, amphibians, crustaceans and fishes (with related photoreceptive molecules present in cephalopods, providing a localized mechanism for light detection across the surface of the body. This form of non-visual photosensitivity may be particularly important for animals that can change their coloration by altering the dispersion of pigments within the chromatophores (pigment containing cells of the skin. Thus, skin coloration may be directly color matched or tuned to both the luminance and spectral properties of the local background environment, thereby facilitating behavioral functions such as camouflage, thermoregulation, and social signaling. This review examines the diversity and sensitivity of opsin-based photopigments present in the skin and considers their putative functional roles in mediating animal behavior. Furthermore, it discusses the potential underlying biochemical and molecular pathways that link shifts in environmental light to both photopigment expression and chromatophore photoresponses. Although photoreception that occurs independently of image formation remains poorly understood, this review highlights the important role of non-visual light detection in facilitating the multiple functions of animal coloration.

  3. Sweat, the driving force behind normal skin: an emerging perspective on functional biology and regulatory mechanisms.

    Science.gov (United States)

    Murota, Hiroyuki; Matsui, Saki; Ono, Emi; Kijima, Akiko; Kikuta, Junichi; Ishii, Masaru; Katayama, Ichiro

    2015-01-01

    The various symptoms associated with excessive or insufficient perspiration can significantly reduce a patient's quality of life. If a versatile and minimally invasive method could be established for returning sweat activity to normalcy, there is no question that it could be used in the treatment of many diseases that are believed to involve perspiration. For this reason, based on an understanding of the sweat-gland control function and sweat activity, it was necessary to conduct a comprehensive search for the factors that control sweating, such as the central and peripheral nerves that control sweat-gland function, the microenvironment surrounding the sweat glands, and lifestyle. We focused on the mechanism by which atopic dermatitis leads to hypohidrosis and confirmed that histamine inhibits acetylcholinergic sweating. Acetylcholine promotes the phosphorylation of glycogen synthesis kinase 3β (GSK3β) in the sweat-gland secretory cells and leads to sensible perspiration. By suppressing the phosphorylation of GSK3β, histamine inhibits the movement of sweat from the sweat-gland secretory cells through the sweat ducts, which could presumably be demonstrated by dynamic observations of the sweat glands using two-photon microscopy. It is expected that the discovery of new factors that control sweat-gland function can contribute to the treatment of diseases associated with dyshidrosis. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  4. Biological post

    OpenAIRE

    Kumar, B. Suresh; Kumar, Senthil; N S Mohan Kumar; Karunakaran, J. V.

    2015-01-01

    Anterior tooth fracture as a result of traumatic injuries, is frequently encountered in endodontic practice. Proper reconstruction of extensively damaged teeth can be achieved through the fragment reattachment procedure known as ?biological restoration.? This case report refers to the esthetics and functional recovery of extensively damaged maxillary central incisor through the preparation and adhesive cementation of ?biological post? in a young patient. Biological post obtained through extra...

  5. The Expanding Universe: Dark Energy

    Energy Technology Data Exchange (ETDEWEB)

    Lincoln, Don [Fermilab; Nord, Brian [Fermilab

    2014-09-01

    In 1998, observations of distant supernovae led physicists that not only was the universe expanding, but the expansion was speeding up. In this article, we describe the evidence for an expanding universe and describe what physicists and cosmologists have learned in the intervening years. The target audience for this article is high school physics teachers and college physics professors at teaching institutions.

  6. Time-resolved diffuse optical tomographic imaging for the provision of both anatomical and functional information about biological tissue

    Science.gov (United States)

    Zhao, Huijuan; Gao, Feng; Tanikawa, Yukari; Homma, Kazuhiro; Yamada, Yukio

    2005-04-01

    We present in vivo images of near-infrared (NIR) diffuse optical tomography (DOT) of human lower legs and forearm to validate the dual functions of a time-resolved (TR) NIR DOT in clinical diagnosis, i.e., to provide anatomical and functional information simultaneously. The NIR DOT system is composed of time-correlated single-photon-counting channels, and the image reconstruction algorithm is based on the modified generalized pulsed spectral technique, which effectively incorporates the TR data with reasonable computation time. The reconstructed scattering images of both the lower legs and the forearm revealed their anatomies, in which the bones were clearly distinguished from the muscles. In the absorption images, some of the blood vessels were observable. In the functional imaging, a subject was requested to do handgripping exercise to stimulate physiological changes in the forearm tissue. The images of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentration changes in the forearm were obtained from the differential images of the absorption at three wavelengths between the exercise and the rest states, which were reconstructed with a differential imaging scheme. These images showed increases in both blood volume and oxyhemoglobin concentration in the arteries and simultaneously showed hypoxia in the corresponding muscles. All the results have demonstrated the capability of TR NIR DOT by reconstruction of the absolute images of the scattering and the absorption with a high spatial resolution that finally provided both the anatomical and functional information inside bulky biological tissues.

  7. Polyamine-Based Thiols in Trypanosomatids: Evolution, Protein Structural Adaptations, and Biological Functions.

    Science.gov (United States)

    Manta, Bruno; Bonilla, Mariana; Fiestas, Lucía; Sturlese, Mattia; Salinas, Gustavo; Bellanda, Massimo; Comini, Marcelo A

    2017-11-27

    Major pathogenic enterobacteria and protozoan parasites from the phylum Euglenozoa, such as trypanosomatids, are endowed with glutathione (GSH)-spermidine (Sp) derivatives that play important roles in signaling and metal and thiol-redox homeostasis. For some Euglenozoa lineages, the GSH-Sp conjugates represent the main redox cosubstrates around which entire new redox systems have evolved. Several proteins underwent molecular adaptations to synthesize and utilize the new polyamine-based thiols. Recent Advances: The genomes of closely related organisms have recently been sequenced, which allows mining and analysis of gene sequences that belong to these peculiar redox systems. Similarly, the three-dimensional structures of several of these proteins have been solved, which allows for comparison with their counterparts in classical redox systems that rely on GSH/glutaredoxin and thioredoxin. The evolutionary and structural aspects related to the emergence and use of GSH-Sp conjugates in Euglenozoa are reviewed focusing on unique structural specializations that proteins developed to use N1,N8-bisglutathionylspermidine (trypanothione) as redox cosubstrate. An updated overview on the biochemical and biological significance of the major enzymatic activities is also provided. A thiol-redox system strictly dependent on trypanothione is a feature unique to trypanosomatids. The physicochemical properties of the polyamine-GSH conjugates were a major driving force for structural adaptation of proteins that use these thiols as ligand and redox cofactor. In fact, the structural differences of indispensable components of this system can be exploited toward selective drug development. Future research should clarify whether additional cellular processes are regulated by the trypanothione system. Antioxid. Redox Signal. 00, 000-000.

  8. Pollination biology of Jacaranda oxyphylla with an emphasis on staminode function.

    Science.gov (United States)

    Guimarães, Elza; di Stasi, Luiz Claudio; Maimoni-Rodella, Rita de Cassia Sindrônia

    2008-11-01

    Bignoniaceae is a Neotropical family with >100 genera, only two of which, Jacaranda and Digomphia, have a developed staminode. Jacaranda oxyphylla, whose flowers possess a conspicuous glandular staminode, is a zoophilous cerrado species. Here, the composition of the secretion of the glandular trichome and the influence of the staminode on the pollination biology and reproductive success of J. oxyphylla were studied. The floral morphology, pollen viability, stigma receptivity, nectar volume and nectar concentration were studied. Compatibility system experiments were performed and floral visitors were observed and identified. Experiments comparing the effect of staminode presence and absence on pollen removal and pollen deposition efficiency were conducted in open-pollinated flowers. Histochemistry, thin-layer chromatography (TLC) and gas chromatography coupled to flame ionization detection (GC-FID) analyses were performed to determine the main chemical components of the staminode's glandular trichome secretion. Flower anthesis lasted 2 d and, despite the low frequency of flower visitation, pollination seemed to be effected mainly by medium-sized Eulaema nigrita and Bombus morio bees, by the small bee Exomalopsis fulvofasciata and occasionally by hummingbirds. Small bees belonging to the genera Ceratina, Augochlora and Trigona were frequent visitors, collecting pollen. Jacaranda oxyphylla is predominantly allogamous. Staminode removal resulted in fewer pollen grains deposited on stigmas but did not affect total pollen removal. The secretion of capitate glandular trichome occurs continually; the main chemical compounds detected histochemically were phenolic and terpenoid (essential oils and resins). Monoterpene cineole, pentacyclic triterpenes and steroids were identified by TLC and GC-FID. The staminode of J. oxyphyllla is multifunctional and its importance for female reproductive success was attributed mainly to the secretion produced by capitate glandular trichomes

  9. Pollination Biology of Jacaranda oxyphylla with an Emphasis on Staminode Function

    Science.gov (United States)

    Guimarães, Elza; di Stasi, Luiz Claudio; Maimoni-Rodella, Rita de Cassia Sindrônia

    2008-01-01

    Background and Aims Bignoniaceae is a Neotropical family with >100 genera, only two of which, Jacaranda and Digomphia, have a developed staminode. Jacaranda oxyphylla, whose flowers possess a conspicuous glandular staminode, is a zoophilous cerrado species. Here, the composition of the secretion of the glandular trichome and the influence of the staminode on the pollination biology and reproductive success of J. oxyphylla were studied. Methods The floral morphology, pollen viability, stigma receptivity, nectar volume and nectar concentration were studied. Compatibility system experiments were performed and floral visitors were observed and identified. Experiments comparing the effect of staminode presence and absence on pollen removal and pollen deposition efficiency were conducted in open-pollinated flowers. Histochemistry, thin-layer chromatography (TLC) and gas chromatography coupled to flame ionization detection (GC–FID) analyses were performed to determine the main chemical components of the staminode's glandular trichome secretion. Key Results Flower anthesis lasted 2 d and, despite the low frequency of flower visitation, pollination seemed to be effected mainly by medium-sized Eulaema nigrita and Bombus morio bees, by the small bee Exomalopsis fulvofasciata and occasionally by hummingbirds. Small bees belonging to the genera Ceratina, Augochlora and Trigona were frequent visitors, collecting pollen. Jacaranda oxyphylla is predominantly allogamous. Staminode removal resulted in fewer pollen grains deposited on stigmas but did not affect total pollen removal. The secretion of capitate glandular trichome occurs continually; the main chemical compounds detected histochemically were phenolic and terpenoid (essential oils and resins). Monoterpene cineole, pentacyclic triterpenes and steroids were identified by TLC and GC–FID. Conclusions The staminode of J. oxyphyllla is multifunctional and its importance for female reproductive success was attributed mainly

  10. Biological functions of hCG and hCG-related molecules

    Directory of Open Access Journals (Sweden)

    Cole Laurence A

    2010-08-01

    Full Text Available Abstract Background hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary. Results and discussion hCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle.

  11. Biological functions of hCG and hCG-related molecules

    Science.gov (United States)

    2010-01-01

    Background hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary. Results and discussion hCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle. PMID:20735820

  12. Molecular mechanisms of the microsomal mixed function oxidases and biological and pathological implications

    Directory of Open Access Journals (Sweden)

    Arthur I. Cederbaum

    2015-04-01

    Full Text Available The cytochrome P450 mixed function oxidase enzymes play a major role in the metabolism of important endogenous substrates as well as in the biotransformation of xenobiotics. The liver P450 system is the most active in metabolism of exogenous substrates. This review briefly describes the liver P450 (CYP mixed function oxidase system with respect to its enzymatic components and functions. Electron transfer by the NADPH-P450 oxidoreductase is required for reduction of the heme of P450, necessary for binding of molecular oxygen. Binding of substrates to P450 produce substrate binding spectra. The P450 catalytic cycle is complex and rate-limiting steps are not clear. Many types of chemical reactions can be catalyzed by P450 enzymes, making this family among the most diverse catalysts known. There are multiple forms of P450s arranged into families based on structural homology. The major drug metabolizing CYPs are discussed with respect to typical substrates, inducers and inhibitors and their polymorphic forms. The composition of CYPs in humans varies considerably among individuals because of sex and age differences, the influence of diet, liver disease, presence of potential inducers and/or inhibitors. Because of such factors and CYP polymorphisms, and overlapping drug specificity, there is a large variability in the content and composition of P450 enzymes among individuals. This can result in large variations in drug metabolism by humans and often can contribute to drug–drug interactions and adverse drug reactions. Because of many of the above factors, especially CYP polymorphisms, there has been much interest in personalized medicine especially with respect to which CYPs and which of their polymorphic forms are present in order to attempt to determine what drug therapy and what dosage would reflect the best therapeutic strategy in treating individual patients.

  13. An Integrated Design, Material, and Fabrication Platform for Engineering Biomechanically and Biologically Functional Soft Tissues.

    Science.gov (United States)

    Bas, Onur; D'Angella, Davide; Baldwin, Jeremy G; Castro, Nathan J; Wunner, Felix M; Saidy, Navid T; Kollmannsberger, Stefan; Reali, Alessandro; Rank, Ernst; De-Juan-Pardo, Elena M; Hutmacher, Dietmar W

    2017-09-06

    We present a design rationale for stretchable soft network composites for engineering tissues that predominantly function under high tensile loads. The convergence of 3D-printed fibers selected from a design library and biodegradable interpenetrating polymer networks (IPNs) result in biomimetic tissue engineered constructs (bTECs) with fully tunable properties that can match specific tissue requirements. We present our technology platform using an exemplary soft network composite model that is characterized to be flexible, yet ∼125 times stronger (E = 3.19 MPa) and ∼100 times tougher (WExt = ∼2000 kJ m(-3)) than its hydrogel counterpart.

  14. Prior weight loss exacerbates the biological drive to gain weight after the loss of ovarian function

    OpenAIRE

    Sherk, Vanessa D; Jackman, Matthew R.; Giles, Erin D.; Higgins, Janine A.; Foright, Rebecca M.; Presby, David M.; Johnson, Ginger C.; Houck, Julie A.; Houser, Jordan L.; Oljira, Robera; MacLean, Paul S.

    2017-01-01

    Abstract Both the history of obesity and weight loss may change how menopause affects metabolic health. The purpose was to determine whether obesity and/or weight loss status alters energy balance (EB) and subsequent weight gain after the loss of ovarian function. Female lean and obese Wistar rats were randomized to 15% weight loss (WL) or ad?libitum fed controls (CON). After the weight loss period, WL rats were kept in EB at the reduced weight for 8?weeks prior to ovariectomy (OVX). After OV...

  15. Bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions.

    Science.gov (United States)

    Beattie, Lynette; Sawtell, Amy; Mann, Jason; Frame, Teija C M; Teal, Bianca; de Labastida Rivera, Fabian; Brown, Najmeeyah; Walwyn-Brown, Katherine; Moore, John W J; MacDonald, Sandy; Lim, Eng-Kiat; Dalton, Jane E; Engwerda, Christian R; MacDonald, Kelli P; Kaye, Paul M

    2016-10-01

    Kupffer cells (KCs), the resident tissue macrophages of the liver, play a crucial role in the clearance of pathogens and other particulate materials that reach the systemic circulation. Recent studies have identified KCs as a yolk sac-derived resident macrophage population that is replenished independently of monocytes in the steady state. Although it is now established that following local tissue injury, bone marrow derived monocytes may infiltrate the tissue and differentiate into macrophages, the extent to which newly differentiated macrophages functionally resemble the KCs they have replaced has not been extensively studied. We studied the two populations of KCs using intravital microscopy, morphometric analysis and gene expression profiling. An ion homeostasis gene signature, including genes associated with scavenger receptor function and extracellular matrix deposition, allowed discrimination between these two KC sub-types. Bone marrow derived "KCs" accumulating as a result of genotoxic injury, resemble but are not identical to their yolk sac counterparts. Reflecting the differential expression of scavenger receptors, yolk sac-derived KCs were more effective at accumulating acetylated low density lipoprotein, whereas surprisingly, they were poorer than bone marrow-derived KCs when assessed for uptake of a range of bacterial pathogens. The two KC populations were almost indistinguishable in regard to i) response to lipopolysaccharide challenge, ii) phagocytosis of effete red blood cells and iii) their ability to contain infection and direct granuloma formation against Leishmania donovani, a KC-tropic intracellular parasite. Bone marrow-derived KCs differentiate locally to resemble yolk sac-derived KC in most but not all respects, with implications for models of infectious diseases, liver injury and bone marrow transplantation. In addition, the gene signature we describe adds to the tools available for distinguishing KC subpopulations based on their ontology

  16. Biochemical Properties and Biological Function of a Monofunctional Microbial Biotin Protein Ligase

    Science.gov (United States)

    Daniels, Kyle G.; Beckett, Dorothy

    2010-01-01

    Biotin protein ligases constitute a family of enzymes that catalyze biotin linkage to biotin-dependent carboxylases. In bacteria these enzymes are functionally divided into two classes; the monofunctional enzymes that only catalyze biotin addition and the bifunctional enzymes that also bind to DNA to regulate transcription initiation. Biochemical and biophysical studies of the bifunctional Escherichia coli ligase suggest that several properties of the enzyme have evolved to support its additional regulatory role. Included among these properties are the order of substrate binding and linkage between oligomeric state and ligand binding. PMID:20499837

  17. Personalized precision radiotherapy by integration of multi-parametric functional and biological imaging in prostate cancer. A feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Thorwarth, Daniela [Tuebingen Univ. (Germany). Section for Biomedical Physics; Notohamiprodjo, Mike [Tuebingen Univ. (Germany). Dept. of Diagnostic and Interventional Radiology; Zips, Daniel; Mueller, Arndt-Christan [Tuebingen Univ. (Germany). Dept. of Radiation Oncology

    2017-05-01

    To increase tumour control probability (TCP) in prostate cancer a method was developed integrating multi-parametric functional and biological information into a dose painting treatment plan aiming focal dose-escalation to tumour sub-volumes. A dose-escalation map was derived considering individual, multi-parametric estimated tumour aggressiveness. Multi-parametric functional imaging (MRI, Choline-/PSMA-/FMISO-PET/CT) was acquired for a high risk prostate cancer patient with a high level of tumour load (cT3b cN0 cM0) indicated by subtotal involvement of prostate including the right seminal vesicle and by PSA-level >100. Probability of tumour presence was determined by a combination of multi-parametric functional image information resulting in a voxel-based map of tumour aggressiveness. This probability map was directly integrated into dose optimization in order to plan for inhomogeneous, biological imaging based dose painting. Histograms of the multi-parametric prescription function were generated in addition to a differential histogram of the planned inhomogeneous doses. Comparison of prescribed doses with planned doses on a voxel level was realized using an effective DVH, containing the ratio of prescribed vs. planned dose for each tumour voxel. Multi-parametric imaging data of PSMA, Choline and FMISO PET/CT as well as ADC maps derived from diffusion weighted MRI were combined to an individual probability map of tumour presence. Voxel-based prescription doses ranged from 75.3 Gy up to 93.4 Gy (median: 79.6 Gy), whereas the planned dose painting doses varied only between 72.5 and 80.0 Gy with a median dose of 75.7 Gy. However, inhomogeneous voxel-based dose prescriptions can only be implemented into a treatment plan until a certain level. Multi-parametric probability based dose painting in prostate cancer is technically and clinically feasible. However, detailed calibration functions to define the necessary probability functions need to be assessed in future

  18. The Role of Soil Biological Function in Regulating Agroecosystem Services and Sustainability in the Quesungual Agroforestry System

    Science.gov (United States)

    Fonte, S.; Pauli, N.; Rousseau, L.; SIX, J. W. U. A.; Barrios, E.

    2014-12-01

    The Quesungual agroforestry system from western Honduras has been increasingly promoted as a promising alternative to traditional slash-and-burn agriculture in tropical dry forest regions of the Americas. Improved residue management and the lack of burning in this system can greatly impact soil biological functioning and a number of key soil-based ecosystem services, yet our understanding of these processes has not been thoroughly integrated to understand system functionality as a whole that can guide improved management. To address this gap, we present a synthesis of various field studies conducted in Central America aimed at: 1) quantifying the influence of the Quesungual agroforestry practices on soil macrofauna abundance and diversity, and 2) understanding how these organisms influence key soil-based ecosystem services that ultimately drive the success of this system. A first set of studies examined the impact of agroecosystem management on soil macrofauna populations, soil fertility and key soil processes. Results suggest that residue inputs (derived from tree biomass pruning), a lack of burning, and high tree densities, lead to conditions that support abundant, diverse soil macrofauna communities under agroforestry, with soil organic carbon content comparable to adjacent forest. Additionally, there is great potential in working with farmers to develop refined soil quality indicators for improved land management. A second line of research explored interactions between residue management and earthworms in the regulation of soil-based ecosystem services. Earthworms are the most prominent ecosystem engineers in these soils. We found that earthworms are key drivers of soil structure maintenance and the stabilization of soil organic matter within soil aggregates, and also had notable impacts on soil nutrient dynamics. However, the impact of earthworms appears to depend on residue management practices, thus indicating the need for an integrated approach for

  19. Studies on the biological functions of CPS1 in AFB1 induced hepatocarcinogenesis.

    Science.gov (United States)

    Yang, Chi; Fu, Rao; Zhuang, Zhenhong; Wang, Shihua

    2016-10-10

    Carbamyl phosphate synthetase 1 (CPS1) was down-regulated in hepatocellular carcinoma (HCC), as treated by aflatoxin B1 (AFB1), a potent hepatocarcinogenesis mycotoxin. In this study, we firstly confirmed that AFB1 down-regulated the expression of CPS1 in a dose-dependent manner. At the meantime, both siRNA knock down of CPS1 and AFB1 treatment inhibited cell proliferation, and induced cell apoptosis. To further analysis the function of CPS1, the interacting proteins of CPS1 were searched by Co-IP, and three interacting proteins including type II cytoskeletal 1 (KRT1), albumin (ALB), and ubiquitin C (UBC) were found. Both KRT1 and ALB were new interacting proteins for CPS1. Our further study showed that CPS1 was regulating interacted and colocalized with KRT1 and ALB, and the intensity correlation was changed by AFB1. KRT1, ALB and CPS1 were all reported to play an important role in differentiation and tissue specialization. These results may offer an increasing understand that CPS1 might have a function in differentiation. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. BIOLOGICAL FUNCTION OF TOMBUSVIRUS-ENCODED SUPPRESSOR OF RNA SILENCING IN PLANTS

    Directory of Open Access Journals (Sweden)

    Omarov R.T.

    2012-08-01

    Full Text Available RNA interference (RNAi plays multiple biological roles in eukaryotic organisms to regulate gene expression. RNAi also operates as a conserved adaptive molecular immune mechanism against invading viruses. The antiviral RNAi pathway is initiated with the generation of virus-derived short-interfering RNAs (siRNAs that are used for subsequent sequence-specific recognition and degradation of the cognate viral RNA molecules. As an efficient counter-defensive strategy, most plant viruses evolved the ability to encode specific proteins capable of interfering with RNAi, and this process is commonly known as RNA silencing suppression. Virus-encoded suppressors of RNAi (VSRs operate at different steps in the RNAi pathway and display distinct biochemical properties that enable these proteins to efficiently interfere with the host-defense system. Tombusvirus-encoded P19 is an important pathogenicity factor, required for symptom development and elicitation of a hypersensitive response in a host-dependent manner. Protein plays a crucial role of TBSV P19 in protecting viral RNA during systemic infection on Nicotiana benthamiana. The X-ray crystallographic studies conducted by two independent groups revealed the existence of a P19-siRNA complex; a conformation whereby caliper tryptophan residues on two subunits of P19 dimers measure and bind 21-nt siRNA duplexes. These structural studies provided the first details on the possible molecular mechanism of any viral suppressor to block RNAi. The association between P19 and siRNAs was also shown to occur in infected plants These and related studies revealed that in general the ability of P19 to efficiently sequester siRNAs influences symptom severity, however this is not a strict correlation in all hosts.The current working model is that during TBSV infection of plants, P19 appropriates abundantly circulating Tombusvirus-derived siRNAs thereby rendering these unavailable to program RISC, to prevent degradation of

  1. Expanding the Bethe/Gauge dictionary

    Science.gov (United States)

    Bullimore, Mathew; Kim, Hee-Cheol; Lukowski, Tomasz

    2017-11-01

    We expand the Bethe/Gauge dictionary between the XXX Heisenberg spin chain and 2d N = (2, 2) supersymmetric gauge theories to include aspects of the algebraic Bethe ansatz. We construct the wave functions of off-shell Bethe states as orbifold defects in the A-twisted supersymmetric gauge theory and study their correlation functions. We also present an alternative description of off-shell Bethe states as boundary conditions in an effective N = 4 supersymmetric quantum mechanics. Finally, we interpret spin chain R-matrices as correlation functions of Janus interfaces for mass parameters in the supersymmetric quantum mechanics.

  2. Impact of AT2-receptor stimulation on vascular biology, kidney function, and blood pressure

    DEFF Research Database (Denmark)

    Danyel, L.A.; Schmerler, P.; Paulis, L.

    2013-01-01

    The angiotensin type 2 receptor (AT2R) and the receptor MAS are receptors within the renin-angiotensin system, which mediate tissue-protective actions such as anti-inflammation, antifibrosis, and antiapoptosis. In recent years, several programs have been launched in order to develop drugs that act...... angiotensin II) and with relevance for blood pressure (BP) regulation or hypertensive end-organ damage. These data will include studies on vasodilation/vasoconstriction in isolated resistance arteries ex vivo, studies on kidney function, studies on vascular remodeling, and studies that measured the net effect...... to attenuate hypertension-induced vascular remodeling and reduce arterial stiffening, which in more chronic settings and together with the natriuretic effect may result in modest lowering of BP. We conclude from these preclinical data that AT2R agonists are not suitable for antihypertensive monotherapy...

  3. Natural Killer Cells in Human Cancer: From Biological Functions to Clinical Applications

    Directory of Open Access Journals (Sweden)

    Estrella Mariel Levy

    2011-01-01

    Full Text Available Natural killer (NK cells are central components of the innate immunity. In murine models, it has been shown that NK cells can control both local tumor growth and metastasis due to their ability to exert direct cellular cytotoxicity without prior sensitization and to secrete immunostimulatory cytokines like IFN-γ. The latter participates in cancer elimination by inhibiting cellular proliferation and angiogenesis, promoting apoptosis, and stimulating the adaptive immune system, and it is instrumental for enhancing Ag processing and presentation. Nevertheless, NK cells display impaired functionality and capability to infiltrate tumors in cancer patients. Also, NK cells are feasible targets of stimulation to participate in immunotherapeutic approaches like antibody-based strategies and adoptive cell transfer. Thus, multiple attempts currently aim to manipulate NK for utilization in the immunotherapy of cancer.

  4. Biological functions of macrophage-derived Wnt5a, and its roles in human diseases.

    Science.gov (United States)

    Shao, Yue; Zheng, Qianqian; Wang, Wei; Xin, Na; Song, Xiaowen; Zhao, Chenghai

    2016-10-11

    Wnt5a is implicated in development and tissue homeostasis by activating β-catenin-independent pathway. Excessive production of Wnt5a is related to some human diseases. Macrophage recruitment is a character of inflammation and cancer, therefore macrophage-derived Wnt5a is supposed to be a player in these conditions. Actually, macrophage-derived Wnt5a maintains macrophage immune function, stimulates pro-inflammatory cytokine release, and induces angiogenesis and lymphangiogenesis. Furthermore, macrophage-derived Wnt5a is involved in insulin resistance, atherosclerosis and cancer. These findings indicate that macrophage-derived Wnt5a may be a target in the treatment of these diseases. Notably, unlike macrophages, the exact role of macrophage-derived Wnt5a in bacterial infection remains largely unknown.

  5. Synthesis and biological evaluation of pyridinium-functionalized carbazole derivatives as promising antibacterial agents.

    Science.gov (United States)

    Wang, Pei-Yi; Fang, He-Shu; Shao, Wu-Bin; Zhou, Jian; Chen, Zhuo; Song, Bao-An; Yang, Song

    2017-09-15

    Various pyridinium-functionalized carbazole derivatives were constructed by coupling the key fragments of carbazole skeleton and pyridinium nucleus in a single molecular architecture. Antibacterial bioassays revealed that some of the title compounds displayed impressive bioactivities against plant pathogens such as Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri with minimal EC50 values of up to 0.4, 0.3, and 0.3mg/L, respectively. These bioactivities were achieved by systematically tuning and optimizing bridging linker, alkyl length of the tailor, and substituents on the carbazole scaffold. Compared with the bioactivity of the lead compound (AP-10), antibacterial efficacy dramatically increased by approximately 13-, 104- and 21-fold. This finding suggested that these compounds can serve as new lead compounds in research on antibacterial chemotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Venus Kinase Receptors: prospects in signalling and biological functions of these invertebrate receptors

    Directory of Open Access Journals (Sweden)

    Colette eDissous

    2014-05-01

    Full Text Available Venus Kinase Receptors (VKRs form a family of invertebrate receptor tyrosine kinases (RTKs initially discovered in the parasitic platyhelminth Schistosoma mansoni. VKRs are single transmembrane receptors which contain an extracellular Venus Flytrap (VFT structure similar to the ligand binding domain of G Protein Coupled Receptors of class C, and an intracellular Tyrosine Kinase domain close to that of Insulin Receptors. VKRs are found in a large variety of invertebrates from cnidarians to echinoderms, and are highly expressed in larval stages and in gonads, suggesting a role of these proteins in embryonic and larval development as well as in reproduction. Vkr gene silencing could demonstrate the function of these receptors in oogenesis as well as in spermatogenesis in Schistosoma .mansoni. VKRs are activated by amino-acids, and highly responsive to arginine. As many other RTKs, they form dimers when activated by ligands and induce intracellular pathways involved in protein synthesis and cellular growth, such as MAPK and PI3K/Akt/S6K pathways. VKRs are not present in vertebrates, nor in some invertebrate species. Questions remain open about the origin of this little-known RTK family in evolution and its role in emergence and specialization of Metazoa. What is the meaning of maintenance or loss of VKR in some phyla or species in terms of development and physiological functions? The presence of VKRs in invertebrates of economical and medical importance, such as pests, vectors of pathogens and platyhelminth parasites, and the implication of these RTKs in gametogenesis and reproduction processes are valuable reasons to consider VKRs as interesting targets in new programs for eradication/ control of pests and infectious diseases, with the main advantage in the case of parasite targeting that VKR counterparts are absent from the vertebrate host kinase panel.

  7. Venus kinase receptors: prospects in signaling and biological functions of these invertebrate kinases.

    Science.gov (United States)

    Dissous, Colette; Morel, Marion; Vanderstraete, Mathieu

    2014-01-01

    Venus kinase receptors (VKRs) form a family of invertebrate receptor tyrosine kinases (RTKs) initially discovered in the parasitic platyhelminth Schistosoma mansoni. VKRs are single transmembrane receptors that contain an extracellular venus fly trap structure similar to the ligand-binding domain of G protein-coupled receptors of class C, and an intracellular tyrosine kinase domain close to that of insulin receptors. VKRs are found in a large variety of invertebrates from cnidarians to echinoderms and are highly expressed in larval stages and in gonads, suggesting a role of these proteins in embryonic and larval development as well as in reproduction. VKR gene silencing could demonstrate the function of these receptors in oogenesis as well as in spermatogenesis in S. mansoni. VKRs are activated by amino acids and are highly responsive to arginine. As many other RTKs, they form dimers when activated by ligands and induce intracellular pa