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

PubMed

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.

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

PubMed

Oborná, I; Fingerová, H

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

Pituitary adenylate cyclase-activating polypeptide: a novel peptide with protean implications.

PubMed

Pisegna, Joseph R; Oh, David S

2007-02-01

The purpose of this review is to highlight the importance of pituitary adenylate cyclase-activating polypeptide in physiological processes and to describe how this peptide is becoming increasingly recognized as having a major role in the body. Since its discovery in 1989, investigators have sought to determine the site of biological activity and the function of pituitary adenylate cyclase-activating polypeptide in maintaining homeostasis. Since its discovery, pituitary adenylate cyclase-activating polypeptide appears to play an important role in the regulation of processes within the central nervous system and gastrointestinal tract, as well in reproductive biology. Pituitary adenylate cyclase-activating polypeptide has been shown to regulate tumor cell growth and to regulate immune function through its effects on T lympocytes. These discoveries suggest the importance of pituitary adenylate cyclase-activating polypeptide in neuronal development, neuronal function, gastrointestinal tract function and reproduction. Future studies will examine more closely the role of pituitary adenylate cyclase-activating polypeptide in regulation of malignantly transformed cells, as well as in regulation of immune function.

Citrate chemistry and biology for biomaterials design.

PubMed

Ma, Chuying; Gerhard, Ethan; Lu, Di; Yang, Jian

2018-05-04

Leveraging the multifunctional nature of citrate in chemistry and inspired by its important role in biological tissues, a class of highly versatile and functional citrate-based materials (CBBs) has been developed via facile and cost-effective polycondensation. CBBs exhibiting tunable mechanical properties and degradation rates, together with excellent biocompatibility and processability, have been successfully applied in vitro and in vivo for applications ranging from soft to hard tissue regeneration, as well as for nanomedicine designs. We summarize in the review, chemistry considerations for CBBs design to tune polymer properties and to introduce functionality with a focus on the most recent advances, biological functions of citrate in native tissues with the new notion of degradation products as cell modulator highlighted, and the applications of CBBs in wound healing, nanomedicine, orthopedic, cardiovascular, nerve and bladder tissue engineering. Given the expansive evidence for citrate's potential in biology and biomaterial science outlined in this review, it is expected that citrate based materials will continue to play an important role in regenerative engineering. Copyright © 2018 Elsevier Ltd. All rights reserved.

Soil microbiology and soil health assessment

USDA-ARS?s Scientific Manuscript database

Soil scientists have long recognized the importance of soil biology in ecological health. In particular, soil microbes are crucial for many soil functions including decomposition, nutrient cycling, synthesis of plant growth regulators, and degradation of synthetic chemicals. Currently, soil biologis...

A rho-binding protein kinase C-like activity is required for the function of protein kinase N in Drosophila development.

PubMed

Betson, Martha; Settleman, Jeffrey

2007-08-01

The Rho GTPases interact with multiple downstream effectors to exert their biological functions, which include important roles in tissue morphogenesis during the development of multicellular organisms. Among the Rho effectors are the protein kinase N (PKN) proteins, which are protein kinase C (PKC)-like kinases that bind activated Rho GTPases. The PKN proteins are well conserved evolutionarily, but their biological role in any organism is poorly understood. We previously determined that the single Drosophila ortholog of mammalian PKN proteins, Pkn, is a Rho/Rac-binding kinase essential for Drosophila development. By performing "rescue" studies with various Pkn mutant constructs, we have defined the domains of Pkn required for its role during Drosophila development. These studies suggested that Rho, but not Rac binding is important for Pkn function in development. In addition, we determined that the kinase domain of PKC53E, a PKC family kinase, can functionally substitute for the kinase domain of Pkn during development, thereby exemplifying the evolutionary strategy of "combining" functional domains to produce proteins with distinct biological activities. Interestingly, we also identified a requirement for Pkn in wing morphogenesis, thereby revealing the first postembryonic function for Pkn.

The evolvability of programmable hardware.

PubMed

Raman, Karthik; Wagner, Andreas

2011-02-06

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

The evolvability of programmable hardware

PubMed Central

Raman, Karthik; Wagner, Andreas

2011-01-01

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

Modelling protein functional domains in signal transduction using Maude

NASA Technical Reports Server (NTRS)

Sriram, M. G.

2003-01-01

Modelling of protein-protein interactions in signal transduction is receiving increased attention in computational biology. This paper describes recent research in the application of Maude, a symbolic language founded on rewriting logic, to the modelling of functional domains within signalling proteins. Protein functional domains (PFDs) are a critical focus of modern signal transduction research. In general, Maude models can simulate biological signalling networks and produce specific testable hypotheses at various levels of abstraction. Developing symbolic models of signalling proteins containing functional domains is important because of the potential to generate analyses of complex signalling networks based on structure-function relationships.

Towards Engineering Biological Systems in a Broader Context.

PubMed

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

2016-02-27

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

Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles.

PubMed

Lötvall, Jan; Hill, Andrew F; Hochberg, Fred; Buzás, Edit I; Di Vizio, Dolores; Gardiner, Christopher; Gho, Yong Song; Kurochkin, Igor V; Mathivanan, Suresh; Quesenberry, Peter; Sahoo, Susmita; Tahara, Hidetoshi; Wauben, Marca H; Witwer, Kenneth W; Théry, Clotilde

2014-01-01

Secreted membrane-enclosed vesicles, collectively called extracellular vesicles (EVs), which include exosomes, ectosomes, microvesicles, microparticles, apoptotic bodies and other EV subsets, encompass a very rapidly growing scientific field in biology and medicine. Importantly, it is currently technically challenging to obtain a totally pure EV fraction free from non-vesicular components for functional studies, and therefore there is a need to establish guidelines for analyses of these vesicles and reporting of scientific studies on EV biology. Here, the International Society for Extracellular Vesicles (ISEV) provides researchers with a minimal set of biochemical, biophysical and functional standards that should be used to attribute any specific biological cargo or functions to EVs.

Applications of systems approaches in the study of rheumatic diseases.

PubMed

Kim, Ki-Jo; Lee, Saseong; Kim, Wan-Uk

2015-03-01

The complex interaction of molecules within a biological system constitutes a functional module. These modules are then acted upon by both internal and external factors, such as genetic and environmental stresses, which under certain conditions can manifest as complex disease phenotypes. Recent advances in high-throughput biological analyses, in combination with improved computational methods for data enrichment, functional annotation, and network visualization, have enabled a much deeper understanding of the mechanisms underlying important biological processes by identifying functional modules that are temporally and spatially perturbed in the context of disease development. Systems biology approaches such as these have produced compelling observations that would be impossible to replicate using classical methodologies, with greater insights expected as both the technology and methods improve in the coming years. Here, we examine the use of systems biology and network analysis in the study of a wide range of rheumatic diseases to better understand the underlying molecular and clinical features.

Caenorhabditis elegans chemical biology: lessons from small molecules

USDA-ARS?s Scientific Manuscript database

How can we complement Caenorhabditis elegans genomics and proteomics with a comprehensive structural and functional annotation of its metabolome? Several lines of evidence indicate that small molecules of largely undetermined structure play important roles in C. elegans biology, including key pathw...

Occurrence, Functions and Biological Significance of Arginine-Rich Proteins.

PubMed

Chandana, Thimmegowda; Venkatesh, Yeldur P

2016-01-01

Arginine, the most basic among the 20 amino acids, occurs less frequently than lysine in proteins despite being coded by six codons. Only a few important proteins of biological significance have been found to be abundant in arginine. It has been established that these arginine-rich proteins have been assigned important roles in the biological systems. Arginine-rich cationic proteins are known to stabilize macromolecular structures by establishing appropriate interactions (salt bridges, hydrogen bonds and cation-π interactions). These proteins are also known to be the key members of many regulatory pathways such as gene expression, chromatin stability, expurgation of introns from naïve mRNA, mRNA splicing, membrane-penetrating activity and pathogenesis-related defense, to name a few. Further, arginine occurs in various combinations with other amino acids (serine, lysine, proline, tryptophan, valine, glycine and glutamic acid) which diversify the potential functions of arginine-rich proteins. Arginine-rich proteins known till date from dietary sources have been described in terms of their structure and functional properties. A variety of activities such as bactericidal, membrane-penetrating, antimicrobial, anti-hypertensive, pro-angiogenic and others have been reported for arginine-rich proteins. This review attempts to collate the occurrence, functions and the biological significance of this unique class of proteins rich in arginine.

Hatch, survival and sensory perception

USDA-ARS?s Scientific Manuscript database

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

Technological Developments in lncRNA Biology.

PubMed

Jathar, Sonali; Kumar, Vikram; Srivastava, Juhi; Tripathi, Vidisha

2017-01-01

It is estimated that more than 90% of the mammalian genome is transcribed as non-coding RNAs. Recent evidences have established that these non-coding transcripts are not junk or just transcriptional noise, but they do serve important biological purpose. One of the rapidly expanding fields of this class of transcripts is the regulatory lncRNAs, which had been a major challenge in terms of their molecular functions and mechanisms of action. The emergence of high-throughput technologies and the development in various conventional approaches have led to the expansion of the lncRNA world. The combination of multidisciplinary approaches has proven to be essential to unravel the complexity of their regulatory networks and helped establish the importance of their existence. Here, we review the current methodologies available for discovering and investigating functions of long non-coding RNAs (lncRNAs) and focus on the powerful technological advancement available to specifically address their functional importance.

Oligodendroglia: metabolic supporters of axons.

PubMed

Morrison, Brett M; Lee, Youngjin; Rothstein, Jeffrey D

2013-12-01

Axons are specialized extensions of neurons that are critical for the organization of the nervous system. To maintain function in axons that often extend some distance from the cell body, specialized mechanisms of energy delivery are likely to be necessary. Over the past decade, greater understanding of human demyelinating diseases and the development of animal models have suggested that oligodendroglia are critical for maintaining the function of axons. In this review, we discuss evidence for the vulnerability of neurons to energy deprivation, the importance of oligodendrocytes for axon function and survival, and recent data suggesting that transfer of energy metabolites from oligodendroglia to axons through monocarboxylate transporter 1 (MCT1) may be critical for the survival of axons. This pathway has important implications both for the basic biology of the nervous system and for human neurological disease. New insights into the role of oligodendroglial biology provide an exciting opportunity for revisions in nervous system biology, understanding myelin-based disorders, and therapeutics development. Copyright © 2013 Elsevier Ltd. All rights reserved.

Phototransformation-Induced Aggregation of Functionalized Single-Walled Carbon Nanotubes: The Importance of Amorphous Carbon

EPA Science Inventory

Single-walled carbon nanotubes (SWCNTs) with proper functionalization are desirable for applications that require dispersion in aqueous and biological environments, and functionalized SWCNTs also serve as building blocks for conjugation with specific molecules in these applicatio...

A Converter from the Systems Biology Markup Language to the Synthetic Biology Open Language.

PubMed

Nguyen, Tramy; Roehner, Nicholas; Zundel, Zach; Myers, Chris J

2016-06-17

Standards are important to synthetic biology because they enable exchange and reproducibility of genetic designs. This paper describes a procedure for converting between two standards: the Systems Biology Markup Language (SBML) and the Synthetic Biology Open Language (SBOL). SBML is a standard for behavioral models of biological systems at the molecular level. SBOL describes structural and basic qualitative behavioral aspects of a biological design. Converting SBML to SBOL enables a consistent connection between behavioral and structural information for a biological design. The conversion process described in this paper leverages Systems Biology Ontology (SBO) annotations to enable inference of a designs qualitative function.

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

USGS Publications Warehouse

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.

Oxidative metabolites of lycopene and their biological functions

USDA-ARS?s Scientific Manuscript database

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...

Fluorescent coumarin-based probe for cysteine and homocysteine with live cell application

NASA Astrophysics Data System (ADS)

Wei, Ling-Fang; Thirumalaivasan, Natesan; Liao, Yu-Cheng; Wu, Shu-Pao

2017-08-01

Cysteine (Cys) and homocysteine (Hcy) are two of important biological thiols and function as important roles in several biological processes. The development of Cys and Hcy probes will help to explore the functions of biothiols in biological systems. In this work, a new coumarin-based probe AC, containing an acryloyl moiety, was developed for Cys and Hcy detection in cells. Cys and Hcy undergo a nucleophilic addition and subsequent cyclization reaction to remove to the acryloyl group and yield a fluorescent product, 7-hydroxylcomuarin. The probe AC showed good selectivity for cysteine and homocysteine over glutathione and other amino acids and had low detection limits of 65 nM for Cys and 79 nM for Hcy, respectively. Additionally, confocal imaging experiments demonstrated that the probe AC can be applied to visualize Cys and Hcy in living cells.

Photobiomodulation on senescence

NASA Astrophysics Data System (ADS)

Liu, Timon Cheng-Yi; Cheng, Lei; Rong, Dong-Liang; Xu, Xiao-Yang; Cui, Li-Ping; Lu, Jian; Deng, Xiao-Yuan; Liu, Song-Hao

2006-09-01

Photobiomodulation (PBM) is an effect oflow intensity monochromatic light or laser irradiation (LIL) on biological systems. which stimulates or inhibits biological functions but does not result in irreducible damage. It has been observed that PBM can suppress cellular senescence, reverse skin photoageing and improve fibromyalgia. In this paper, the biological information model of photobiomodulation (BIMP) is used to discuss its mechanism. Cellular senescence can result from short, dysfunctional telomeres, oxidative stress, or oncogene expression, and may contribute to aging so that it can be seen as a decline of cellular function in which cAMP plays an important role, which provide a foundation for PBM on senescence since cellular senescence is a reasonable model of senescence and PBM is a cellular rehabilitation in which cAMP also plays an important role according to BIMP. The PBM in reversing skin photoageing and improving fibromyalgia are then discussed in detail.

Lipid Cell Biology: A Focus on Lipids in Cell Division.

PubMed

Storck, Elisabeth M; Özbalci, Cagakan; Eggert, Ulrike S

2018-06-20

Cells depend on hugely diverse lipidomes for many functions. The actions and structural integrity of the plasma membrane and most organelles also critically depend on membranes and their lipid components. Despite the biological importance of lipids, our understanding of lipid engagement, especially the roles of lipid hydrophobic alkyl side chains, in key cellular processes is still developing. Emerging research has begun to dissect the importance of lipids in intricate events such as cell division. This review discusses how these structurally diverse biomolecules are spatially and temporally regulated during cell division, with a focus on cytokinesis. We analyze how lipids facilitate changes in cellular morphology during division and how they participate in key signaling events. We identify which cytokinesis proteins are associated with membranes, suggesting lipid interactions. More broadly, we highlight key unaddressed questions in lipid cell biology and techniques, including mass spectrometry, advanced imaging, and chemical biology, which will help us gain insights into the functional roles of lipids.

A Graph Approach to Mining Biological Patterns in the Binding Interfaces.

PubMed

Cheng, Wen; Yan, Changhui

2017-01-01

Protein-RNA interactions play important roles in the biological systems. Searching for regular patterns in the Protein-RNA binding interfaces is important for understanding how protein and RNA recognize each other and bind to form a complex. Herein, we present a graph-mining method for discovering biological patterns in the protein-RNA interfaces. We represented known protein-RNA interfaces using graphs and then discovered graph patterns enriched in the interfaces. Comparison of the discovered graph patterns with UniProt annotations showed that the graph patterns had a significant overlap with residue sites that had been proven crucial for the RNA binding by experimental methods. Using 200 patterns as input features, a support vector machine method was able to classify protein surface patches into RNA-binding sites and non-RNA-binding sites with 84.0% accuracy and 88.9% precision. We built a simple scoring function that calculated the total number of the graph patterns that occurred in a protein-RNA interface. That scoring function was able to discriminate near-native protein-RNA complexes from docking decoys with a performance comparable with that of a state-of-the-art complex scoring function. Our work also revealed possible patterns that might be important for binding affinity.

Optimal network alignment with graphlet degree vectors.

PubMed

Milenković, Tijana; Ng, Weng Leong; Hayes, Wayne; Przulj, Natasa

2010-06-30

Important biological information is encoded in the topology of biological networks. Comparative analyses of biological networks are proving to be valuable, as they can lead to transfer of knowledge between species and give deeper insights into biological function, disease, and evolution. We introduce a new method that uses the Hungarian algorithm to produce optimal global alignment between two networks using any cost function. We design a cost function based solely on network topology and use it in our network alignment. Our method can be applied to any two networks, not just biological ones, since it is based only on network topology. We use our new method to align protein-protein interaction networks of two eukaryotic species and demonstrate that our alignment exposes large and topologically complex regions of network similarity. At the same time, our alignment is biologically valid, since many of the aligned protein pairs perform the same biological function. From the alignment, we predict function of yet unannotated proteins, many of which we validate in the literature. Also, we apply our method to find topological similarities between metabolic networks of different species and build phylogenetic trees based on our network alignment score. The phylogenetic trees obtained in this way bear a striking resemblance to the ones obtained by sequence alignments. Our method detects topologically similar regions in large networks that are statistically significant. It does this independent of protein sequence or any other information external to network topology.

Biomimetic cellular metals-using hierarchical structuring for energy absorption.

PubMed

Bührig-Polaczek, A; Fleck, C; Speck, T; Schüler, P; Fischer, S F; Caliaro, M; Thielen, M

2016-07-19

Fruit walls as well as nut and seed shells typically perform a multitude of functions. One of the biologically most important functions consists in the direct or indirect protection of the seeds from mechanical damage or other negative environmental influences. This qualifies such biological structures as role models for the development of new materials and components that protect commodities and/or persons from damage caused for example by impacts due to rough handling or crashes. We were able to show how the mechanical properties of metal foam based components can be improved by altering their structure on various hierarchical levels inspired by features and principles important for the impact and/or puncture resistance of the biological role models, rather than by tuning the properties of the bulk material. For this various investigation methods have been established which combine mechanical testing with different imaging methods, as well as with in situ and ex situ mechanical testing methods. Different structural hierarchies especially important for the mechanical deformation and failure behaviour of the biological role models, pomelo fruit (Citrus maxima) and Macadamia integrifolia, were identified. They were abstracted and transferred into corresponding structural principles and thus hierarchically structured bio-inspired metal foams have been designed. A production route for metal based bio-inspired structures by investment casting was successfully established. This allows the production of complex and reliable structures, by implementing and combining different hierarchical structural elements found in the biological concept generators, such as strut design and integration of fibres, as well as by minimising casting defects. To evaluate the structural effects, similar investigation methods and mechanical tests were applied to both the biological role models and the metallic foams. As a result an even deeper quantitative understanding of the form-structure-function relationship of the biological concept generators as well as the bio-inspired metal foams was achieved, on deeper hierarchical levels and overarching different levels.

Teaching Electrostatics and Entropy in Introductory Physics

NASA Astrophysics Data System (ADS)

Reeves, Mark

Entropy changes underlie the physics that dominates biological interactions. Indeed, introductory biology courses often begin with an exploration of the qualities of water that are important to living systems. However, one idea that is not explicitly addressed in most introductory physics or biology courses is important contribution of the entropy in driving fundamental biological processes towards equilibrium. I will present material developed to teach electrostatic screening in solutions and the function of nerve cells where entropic effects act to counterbalance electrostatic attraction. These ideas are taught in an introductory, calculus-based physics course to biomedical engineers using SCALEUP pedagogy. Results of student mastering of complex problems that cross disciplinary boundaries between biology and physics, as well as the challenges that they face in learning this material will be presented.

Accurate evaluation and analysis of functional genomics data and methods

PubMed Central

Greene, Casey S.; Troyanskaya, Olga G.

2016-01-01

The development of technology capable of inexpensively performing large-scale measurements of biological systems has generated a wealth of data. Integrative analysis of these data holds the promise of uncovering gene function, regulation, and, in the longer run, understanding complex disease. However, their analysis has proved very challenging, as it is difficult to quickly and effectively assess the relevance and accuracy of these data for individual biological questions. Here, we identify biases that present challenges for the assessment of functional genomics data and methods. We then discuss evaluation methods that, taken together, begin to address these issues. We also argue that the funding of systematic data-driven experiments and of high-quality curation efforts will further improve evaluation metrics so that they more-accurately assess functional genomics data and methods. Such metrics will allow researchers in the field of functional genomics to continue to answer important biological questions in a data-driven manner. PMID:22268703

Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins.

PubMed

Uversky, Vladimir N

2016-03-25

Biologically active but floppy proteins represent a new reality of modern protein science. These intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered and intrinsically disordered protein regions (IDPRs) constitute a noticeable part of any given proteome. Functionally, they complement ordered proteins, and their conformational flexibility and structural plasticity allow them to perform impossible tricks and be engaged in biological activities that are inaccessible to well folded proteins with their unique structures. The major goals of this minireview are to show that, despite their simplified amino acid sequences, IDPs/IDPRs are complex entities often resembling chaotic systems, are structurally and functionally heterogeneous, and can be considered an important part of the structure-function continuum. Furthermore, IDPs/IDPRs are everywhere, and are ubiquitously engaged in various interactions characterized by a wide spectrum of binding scenarios and an even wider spectrum of structural and functional outputs. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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

PubMed

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

2015-02-15

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

Students' Learning Activities While Studying Biological Process Diagrams

ERIC Educational Resources Information Center

Kragten, Marco; Admiraal, Wilfried; Rijlaarsdam, Gert

2015-01-01

Process diagrams describe how a system functions (e.g. photosynthesis) and are an important type of representation in Biology education. In the present study, we examined students' learning activities while studying process diagrams, related to their resulting comprehension of these diagrams. Each student completed three learning tasks. Verbal…

Biomonitoring: Uses and Considerations for Assessing Non-Occupational Human Exposure to Pesticides

EPA Science Inventory

Biomonitoring is an important tool that can be used to evaluate human exposure to pesticides by measuring the levels of pesticides, pesticide metabolites, or altered biological structures or functions in biological specimens or tissues (Barr et al., 2005b; Needham et al., 2005, 2...

Aminoglycosides: Molecular Insights on the Recognition of RNA and Aminoglycoside Mimics

PubMed Central

Chittapragada, Maruthi; Roberts, Sarah; Ham, Young Wan

2009-01-01

RNA is increasingly recognized for its significant functions in biological systems and has recently become an important molecular target for therapeutics development. Aminoglycosides, a large class of clinically significant antibiotics, exert their biological functions by binding to prokaryotic ribosomal RNA (rRNA) and interfering with protein translation, resulting in bacterial cell death. They are also known to bind to viral mRNAs such as HIV-1 RRE and TAR. Consequently, aminoglycosides are accepted as the single most important model in understanding the principles that govern small molecule-RNA recognition, which is essential for the development of novel antibacterial, antiviral or even anti-oncogenic agents. This review outlines the chemical structures and mechanisms of molecular recognition and antibacterial activity of aminoglycosides and various aminoglycoside mimics that have recently been devised to improve biological efficacy, binding affinity and selectivity, or to circumvent bacterial resistance. PMID:19812740

The Redox Chemistry and Chemical Biology of H2S, Hydropersulfides and Derived Species: Implications to Their Possible Biological Activity and Utility

PubMed Central

Ono, Katsuhiko; Akaike, Takaake; Sawa, Tomohiro; Kumagai, Yoshito; Wink, David A.; Tantillo, Dean J.; Hobbs, Adrian J.; Nagy, Peter; Xian, Ming; Lin, Joseph; Fukuto, Jon M.

2014-01-01

Hydrogen sulfide (H2S) is an endogenously generated and putative signaling/effector molecule. In spite of its numerous reported functions, the chemistry by which it elicits its functions is not understood. Moreover, recent studies allude to the existence of other sulfur species besides H2S that may play critical physiological roles. Herein, the basic chemical biology of H2S as well as other related or derived species is discussed and reviewed. A particular focus of this review are the per- and poly-sulfides which are likely in equilibrium with free H2S and which may be important biological effectors themselves. PMID:25229186

Vitamin C: electron emission, free radicals and biological versatility.

PubMed

Getoff, Nikola

2013-01-01

The many-sided biological role of vitamin C (ascorbate) is briefly illustrated by specific examples. It is demonstrated that in aqueous solutions, vitamin C emits solvated electrons (e(aq)(-)), when excited in single state. Vitamin C can also react with e(aq)(-) as well as transfer them to other biological systems and thereby acts as efficient electron mediator. Based on its chemical and biological properties, it is clear that vitamin C plays a very important role in various functions in the organism alongside biochemical processes.

A promising future for integrative biodiversity research: an increased role of scale-dependency and functional biology.

PubMed

Price, S A; Schmitz, L

2016-04-05

Studies into the complex interaction between an organism and changes to its biotic and abiotic environment are fundamental to understanding what regulates biodiversity. These investigations occur at many phylogenetic, temporal and spatial scales and within a variety of biological and geological disciplines but often in relative isolation. This issue focuses on what can be achieved when ecological mechanisms are integrated into analyses of deep-time biodiversity patterns through the union of fossil and extant data and methods. We expand upon this perspective to argue that, given its direct relevance to the current biodiversity crisis, greater integration is needed across biodiversity research. We focus on the need to understand scaling effects, how lower-level ecological and evolutionary processes scale up and vice versa, and the importance of incorporating functional biology. Placing function at the core of biodiversity research is fundamental, as it establishes how an organism interacts with its abiotic and biotic environment and it is functional diversity that ultimately determines important ecosystem processes. To achieve full integration, concerted and ongoing efforts are needed to build a united and interactive community of biodiversity researchers, with education and interdisciplinary training at its heart. © 2016 The Author(s).

A computational platform to maintain and migrate manual functional annotations for BioCyc databases.

PubMed

Walsh, Jesse R; Sen, Taner Z; Dickerson, Julie A

2014-10-12

BioCyc databases are an important resource for information on biological pathways and genomic data. Such databases represent the accumulation of biological data, some of which has been manually curated from literature. An essential feature of these databases is the continuing data integration as new knowledge is discovered. As functional annotations are improved, scalable methods are needed for curators to manage annotations without detailed knowledge of the specific design of the BioCyc database. We have developed CycTools, a software tool which allows curators to maintain functional annotations in a model organism database. This tool builds on existing software to improve and simplify annotation data imports of user provided data into BioCyc databases. Additionally, CycTools automatically resolves synonyms and alternate identifiers contained within the database into the appropriate internal identifiers. Automating steps in the manual data entry process can improve curation efforts for major biological databases. The functionality of CycTools is demonstrated by transferring GO term annotations from MaizeCyc to matching proteins in CornCyc, both maize metabolic pathway databases available at MaizeGDB, and by creating strain specific databases for metabolic engineering.

A promising future for integrative biodiversity research: an increased role of scale-dependency and functional biology

PubMed Central

Schmitz, L.

2016-01-01

Studies into the complex interaction between an organism and changes to its biotic and abiotic environment are fundamental to understanding what regulates biodiversity. These investigations occur at many phylogenetic, temporal and spatial scales and within a variety of biological and geological disciplines but often in relative isolation. This issue focuses on what can be achieved when ecological mechanisms are integrated into analyses of deep-time biodiversity patterns through the union of fossil and extant data and methods. We expand upon this perspective to argue that, given its direct relevance to the current biodiversity crisis, greater integration is needed across biodiversity research. We focus on the need to understand scaling effects, how lower-level ecological and evolutionary processes scale up and vice versa, and the importance of incorporating functional biology. Placing function at the core of biodiversity research is fundamental, as it establishes how an organism interacts with its abiotic and biotic environment and it is functional diversity that ultimately determines important ecosystem processes. To achieve full integration, concerted and ongoing efforts are needed to build a united and interactive community of biodiversity researchers, with education and interdisciplinary training at its heart. PMID:26977068

Chemoenzymatic Labeling of Proteins: Techniques and Approaches

PubMed Central

Rashidian, Mohammad; Dozier, Jonathan K.; Distefano, Mark D.

2013-01-01

Site-specific modification of proteins is a major challenge in modern chemical biology due to the large number of reactive functional groups typically present in polypeptides. Because of its importance in biology and medicine, the development of methods for site-specific modification of proteins is an area of intense research. Selective protein modification procedures have been useful for oriented protein immobilization, for studies of naturally-occurring post-translational modifications, for creating antibody-drug conjugates, for the introduction of fluorophores and other small molecules on to proteins, for examining protein structure, folding, dynamics and protein-protein interactions and for the preparation of protein-polymer conjugates. One of the most important approaches for protein labeling is to incorporate bioorthogonal functionalities into proteins at specific sites via enzymatic reactions. The incorporated tags then enable reactions that are chemoselective, whose functional groups are not only inert in biological media, but also do not occur natively in proteins or other macromolecules. This review article summarizes the enzymatic strategies, which enable site-specific functionalization of proteins with a variety of different functional groups. The enzymes covered in this review include formylglycine generating enzyme, sialyltransferases, phosphopantetheinyltransferases, O-GlcNAc post-translational modification, sortagging, transglutaminase, farnesyltransferase, biotin ligase, lipoic acid ligase and N-myristoyl transferase. PMID:23837885

Using Yeast to Determine the Functional Consequences of Mutations in the Human p53 Tumor Suppressor Gene: An Introductory Course-Based Undergraduate Research Experience in Molecular and Cell Biology

ERIC Educational Resources Information Center

Hekmat-Scafe, Daria S.; Brownell, Sara E.; Seawell, Patricia Chandler; Malladi, Shyamala; Imam, Jamie F. Conklin; Singla, Veena; Bradon, Nicole; Cyert, Martha S.; Stearns, Tim

2017-01-01

The opportunity to engage in scientific research is an important, but often neglected, component of undergraduate training in biology. We describe the curriculum for an innovative, course-based undergraduate research experience (CURE) appropriate for a large, introductory cell and molecular biology laboratory class that leverages students' high…

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

PubMed

Sakaki, Michiko; Niki, Kazuhisa; Mather, Mara

2012-03-01

The present study addressed the hypothesis that emotional stimuli relevant to survival or reproduction (biologically emotional stimuli) automatically affect cognitive processing (e.g., attention, memory), while those relevant to social life (socially emotional stimuli) require elaborative processing to modulate attention and memory. Results of our behavioral studies showed that (1) biologically emotional images hold attention more strongly than do socially emotional images, (2) memory for biologically emotional images was enhanced even with limited cognitive resources, but (3) memory for socially emotional images was enhanced only when people had sufficient cognitive resources at encoding. Neither images' subjective arousal nor their valence modulated these patterns. A subsequent functional magnetic resonance imaging study revealed that biologically emotional images induced stronger activity in the visual cortex and greater functional connectivity between the amygdala and visual cortex than did socially emotional images. These results suggest that the interconnection between the amygdala and visual cortex supports enhanced attention allocation to biological stimuli. In contrast, socially emotional images evoked greater activity in the medial prefrontal cortex (MPFC) and yielded stronger functional connectivity between the amygdala and MPFC than did biological images. Thus, it appears that emotional processing of social stimuli involves elaborative processing requiring frontal lobe activity.

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

PubMed Central

Sakaki, Michiko; Niki, Kazuhisa; Mather, Mara

2012-01-01

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

Contact nanomechanical measurements with the AFM

NASA Astrophysics Data System (ADS)

Geisse, Nicholas

2013-03-01

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

Functional Imaging Biomarkers: Potential to Guide an Individualised Approach to Radiotherapy.

PubMed

Prestwich, R J D; Vaidyanathan, S; Scarsbrook, A F

2015-10-01

The identification of robust prognostic and predictive biomarkers would transform the ability to implement an individualised approach to radiotherapy. In this regard, there has been a surge of interest in the use of functional imaging to assess key underlying biological processes within tumours and their response to therapy. Importantly, functional imaging biomarkers hold the potential to evaluate tumour heterogeneity/biology both spatially and temporally. An ever-increasing range of functional imaging techniques is now available primarily involving positron emission tomography and magnetic resonance imaging. Small-scale studies across multiple tumour types have consistently been able to correlate changes in functional imaging parameters during radiotherapy with disease outcomes. Considerable challenges remain before the implementation of functional imaging biomarkers into routine clinical practice, including the inherent temporal variability of biological processes within tumours, reproducibility of imaging, determination of optimal imaging technique/combinations, timing during treatment and design of appropriate validation studies. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Hierarchical Feedback Modules and Reaction Hubs in Cell Signaling Networks

PubMed Central

Xu, Jianfeng; Lan, Yueheng

2015-01-01

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

Pathophysiological significance and therapeutic applications of snake venom protease inhibitors.

PubMed

Thakur, Rupamoni; Mukherjee, Ashis K

2017-06-01

Protease inhibitors are important constituents of snake venom and play important roles in the pathophysiology of snakebite. Recently, research on snake venom protease inhibitors has provided valuable information to decipher the molecular details of various biological processes and offer insight for the development of some therapeutically important molecules from snake venom. The process of blood coagulation and fibrinolysis, in addition to affecting platelet function, are well known as the major targets of several snake venom protease inhibitors. This review summarizes the structure-functional aspects of snake venom protease inhibitors that have been described to date. Because diverse biological functions have been demonstrated by protease inhibitors, a comparative overview of their pharmacological and pathophysiological properties is also highlighted. In addition, since most snake venom protease inhibitors are non-toxic on their own, this review evaluates the different roles of individual protease inhibitors that could lead to the identification of drug candidates and diagnostic molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

Selective enrichment of metal-binding proteins based on magnetic core/shell microspheres functionalized with metal cations.

PubMed

Fang, Caiyun; Zhang, Lei; Zhang, Xiaoqin; Lu, Haojie

2015-06-21

Metal binding proteins play many important roles in a broad range of biological processes. Characterization of metal binding proteins is important for understanding their structure and biological functions, thus leading to a clear understanding of metal associated diseases. The present study is the first to investigate the effectiveness of magnetic microspheres functionalized with metal cations (Ca(2+), Cu(2+), Zn(2+) and Fe(3+)) as the absorbent matrix in IMAC technology to enrich metal containing/binding proteins. The putative metal binding proteins in rat liver were then globally characterized by using this strategy which is very easy to handle and can capture a number of metal binding proteins effectively. In total, 185 putative metal binding proteins were identified from rat liver including some known less abundant and membrane-bound metal binding proteins such as Plcg1, Acsl5, etc. The identified proteins are involved in many important processes including binding, catalytic activity, translation elongation factor activity, electron carrier activity, and so on.

CytoCluster: A Cytoscape Plugin for Cluster Analysis and Visualization of Biological Networks.

PubMed

Li, Min; Li, Dongyan; Tang, Yu; Wu, Fangxiang; Wang, Jianxin

2017-08-31

Nowadays, cluster analysis of biological networks has become one of the most important approaches to identifying functional modules as well as predicting protein complexes and network biomarkers. Furthermore, the visualization of clustering results is crucial to display the structure of biological networks. Here we present CytoCluster, a cytoscape plugin integrating six clustering algorithms, HC-PIN (Hierarchical Clustering algorithm in Protein Interaction Networks), OH-PIN (identifying Overlapping and Hierarchical modules in Protein Interaction Networks), IPCA (Identifying Protein Complex Algorithm), ClusterONE (Clustering with Overlapping Neighborhood Expansion), DCU (Detecting Complexes based on Uncertain graph model), IPC-MCE (Identifying Protein Complexes based on Maximal Complex Extension), and BinGO (the Biological networks Gene Ontology) function. Users can select different clustering algorithms according to their requirements. The main function of these six clustering algorithms is to detect protein complexes or functional modules. In addition, BinGO is used to determine which Gene Ontology (GO) categories are statistically overrepresented in a set of genes or a subgraph of a biological network. CytoCluster can be easily expanded, so that more clustering algorithms and functions can be added to this plugin. Since it was created in July 2013, CytoCluster has been downloaded more than 9700 times in the Cytoscape App store and has already been applied to the analysis of different biological networks. CytoCluster is available from http://apps.cytoscape.org/apps/cytocluster.

CytoCluster: A Cytoscape Plugin for Cluster Analysis and Visualization of Biological Networks

PubMed Central

Li, Min; Li, Dongyan; Tang, Yu; Wang, Jianxin

2017-01-01

Nowadays, cluster analysis of biological networks has become one of the most important approaches to identifying functional modules as well as predicting protein complexes and network biomarkers. Furthermore, the visualization of clustering results is crucial to display the structure of biological networks. Here we present CytoCluster, a cytoscape plugin integrating six clustering algorithms, HC-PIN (Hierarchical Clustering algorithm in Protein Interaction Networks), OH-PIN (identifying Overlapping and Hierarchical modules in Protein Interaction Networks), IPCA (Identifying Protein Complex Algorithm), ClusterONE (Clustering with Overlapping Neighborhood Expansion), DCU (Detecting Complexes based on Uncertain graph model), IPC-MCE (Identifying Protein Complexes based on Maximal Complex Extension), and BinGO (the Biological networks Gene Ontology) function. Users can select different clustering algorithms according to their requirements. The main function of these six clustering algorithms is to detect protein complexes or functional modules. In addition, BinGO is used to determine which Gene Ontology (GO) categories are statistically overrepresented in a set of genes or a subgraph of a biological network. CytoCluster can be easily expanded, so that more clustering algorithms and functions can be added to this plugin. Since it was created in July 2013, CytoCluster has been downloaded more than 9700 times in the Cytoscape App store and has already been applied to the analysis of different biological networks. CytoCluster is available from http://apps.cytoscape.org/apps/cytocluster. PMID:28858211

Endocrine Disruptors (Chapter 14) in Mammalian Toxicology Book

EPA Science Inventory

Endocrine disrupting chemicals (EDCs) are exogenous substances that alter endocrine system function(s) and consequently cause adverse health effects in intact organisms or its progeny. The endocrine system is important for a wide range of biological processes, from normal cell si...

State-of-the-art technologies, current opinions and developments, and novel findings: news from the field of histochemistry and cell biology.

PubMed

Asan, Esther; Drenckhahn, Detlev

2008-12-01

Investigations of cell and tissue structure and function using innovative methods and approaches have again yielded numerous exciting findings in recent months and have added important data to current knowledge, inspiring new ideas and hypotheses in various fields of modern life sciences. Topics and contents of comprehensive expert reviews covering different aspects in methodological advances, cell biology, tissue function and morphology, and novel findings reported in original papers are summarized in the present review.

Expanding the biological periodic table.

PubMed

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.

Structural Biology for A-Level Students

ERIC Educational Resources Information Center

Philip, Judith

2013-01-01

The relationship between the structure and function of proteins is an important area in biochemistry. Pupils studying A-level Biology are introduced to the four levels of protein structure (primary, secondary, tertiary and quaternary) and how these can be used to describe the progressive folding of a chain of amino acid residues to a final,…

Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins*

PubMed Central

2016-01-01

Biologically active but floppy proteins represent a new reality of modern protein science. These intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered and intrinsically disordered protein regions (IDPRs) constitute a noticeable part of any given proteome. Functionally, they complement ordered proteins, and their conformational flexibility and structural plasticity allow them to perform impossible tricks and be engaged in biological activities that are inaccessible to well folded proteins with their unique structures. The major goals of this minireview are to show that, despite their simplified amino acid sequences, IDPs/IDPRs are complex entities often resembling chaotic systems, are structurally and functionally heterogeneous, and can be considered an important part of the structure-function continuum. Furthermore, IDPs/IDPRs are everywhere, and are ubiquitously engaged in various interactions characterized by a wide spectrum of binding scenarios and an even wider spectrum of structural and functional outputs. PMID:26851286

Leveraging advances in biology to design biomaterials

NASA Astrophysics Data System (ADS)

Darnell, Max; Mooney, David J.

2017-12-01

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

Linear ordered collagen scaffolds loaded with collagen-binding basic fibroblast growth factor facilitate recovery of sciatic nerve injury in rats.

PubMed

Ma, Fukai; Xiao, Zhifeng; Chen, Bing; Hou, Xianglin; Dai, Jianwu; Xu, Ruxiang

2014-04-01

Natural biological functional scaffolds, consisting of biological materials filled with promoting elements, provide a promising strategy for the regeneration of peripheral nerve defects. Collagen conduits have been used widely due to their excellent biological properties. Linear ordered collagen scaffold (LOCS) fibers are good lumen fillers that can guide nerve regeneration in an ordered direction. In addition, basic fibroblast growth factor (bFGF) is important in the recovery of nerve injury. However, the traditional method for delivering bFGF to the lesion site has no long-term effect because of its short half-life and rapid diffusion. Therefore, we fused a specific collagen-binding domain (CBD) peptide to the N-terminal of native basic fibroblast growth factor (NAT-bFGF) to retain bFGF on the collagen scaffolds. In this study, a natural biological functional scaffold was constructed using collagen tubes filled with collagen-binding bFGF (CBD-bFGF)-loaded LOCS to promote regeneration in a 5-mm rat sciatic nerve transection model. Functional evaluation, histological investigation, and morphometric analysis indicated that the natural biological functional scaffold retained more bFGF at the injury site, guided axon growth, and promoted nerve regeneration as well as functional restoration.

Yeast mitochondria: an overview of mitochondrial biology and the potential of mitochondrial systems biology.

PubMed

Malina, Carl; Larsson, Christer; Nielsen, Jens

2018-08-01

Mitochondria are dynamic organelles of endosymbiotic origin that are essential components of eukaryal cells. They contain their own genetic machinery, have multicopy genomes and like their bacterial ancestors they consist of two membranes. However, the majority of the ancestral genome has been lost or transferred to the nuclear genome of the host, preserving only a core set of genes involved in oxidative phosphorylation. Mitochondria perform numerous biological tasks ranging from bioenergetics to production of protein co-factors, including heme and iron-sulfur clusters. Due to the importance of mitochondria in many cellular processes, mitochondrial dysfunction is implicated in a wide variety of human disorders. Much of our current knowledge on mitochondrial function and dysfunction comes from studies using Saccharomyces cerevisiae. This yeast has good fermenting capacity, rendering tolerance to mutations that inactivate oxidative phosphorylation and complete loss of mitochondrial DNA. Here, we review yeast mitochondrial metabolism and function with focus on S. cerevisiae and its contribution in understanding mitochondrial biology. We further review how systems biology studies, including mathematical modeling, has allowed gaining new insight into mitochondrial function, and argue that this approach may enable us to gain a holistic view on how mitochondrial function interacts with different cellular processes.

Recent Developments in the Application of Biologically Inspired Computation to Chemical Sensing

NASA Astrophysics Data System (ADS)

Marco, S.; Gutierrez-Gálvez, A.

2009-05-01

Biological olfaction outperforms chemical instrumentation in specificity, response time, detection limit, coding capacity, time stability, robustness, size, power consumption, and portability. This biological function provides outstanding performance due, to a large extent, to the unique architecture of the olfactory pathway, which combines a high degree of redundancy, an efficient combinatorial coding along with unmatched chemical information processing mechanisms. The last decade has witnessed important advances in the understanding of the computational primitives underlying the functioning of the olfactory system. In this work, the state of the art concerning biologically inspired computation for chemical sensing will be reviewed. Instead of reviewing the whole body of computational neuroscience of olfaction, we restrict this review to the application of models to the processing of real chemical sensor data.

Dynamics of biological systems: role of systems biology in medical research.

PubMed

Assmus, Heike E; Herwig, Ralf; Cho, Kwang-Hyun; Wolkenhauer, Olaf

2006-11-01

Cellular systems are networks of interacting components that change with time in response to external and internal events. Studying the dynamic behavior of these networks is the basis for an understanding of cellular functions and disease mechanisms. Quantitative time-series data leading to meaningful models can improve our knowledge of human physiology in health and disease, and aid the search for earlier diagnoses, better therapies and a healthier life. The advent of systems biology is about to take the leap into clinical research and medical applications. This review emphasizes the importance of a dynamic view and understanding of cell function. We discuss the potential for computer-aided mathematical modeling of biological systems in medical research with examples from some of the major therapeutic areas: cancer, cardiovascular, diabetic and neurodegenerative medicine.

New Ways of Thinking about (and Teaching about) Intestinal Epithelial Function

ERIC Educational Resources Information Center

Barrett, Kim E.

2008-01-01

This article summarizes a presentation made at the Teaching Refresher Course of the American Physiological Society, which was held at the Experimental Biology meeting in 2007. The intestinal epithelium has important ion transport and barrier functions that contribute pivotally to normal physiological functioning of the intestine and other body…

Glycan array data management at Consortium for Functional Glycomics.

PubMed

Venkataraman, Maha; Sasisekharan, Ram; Raman, Rahul

2015-01-01

Glycomics or the study of structure-function relationships of complex glycans has reshaped post-genomics biology. Glycans mediate fundamental biological functions via their specific interactions with a variety of proteins. Recognizing the importance of glycomics, large-scale research initiatives such as the Consortium for Functional Glycomics (CFG) were established to address these challenges. Over the past decade, the Consortium for Functional Glycomics (CFG) has generated novel reagents and technologies for glycomics analyses, which in turn have led to generation of diverse datasets. These datasets have contributed to understanding glycan diversity and structure-function relationships at molecular (glycan-protein interactions), cellular (gene expression and glycan analysis), and whole organism (mouse phenotyping) levels. Among these analyses and datasets, screening of glycan-protein interactions on glycan array platforms has gained much prominence and has contributed to cross-disciplinary realization of the importance of glycomics in areas such as immunology, infectious diseases, cancer biomarkers, etc. This manuscript outlines methodologies for capturing data from glycan array experiments and online tools to access and visualize glycan array data implemented at the CFG.

Analyzing cell fate control by cytokines through continuous single cell biochemistry.

PubMed

Rieger, Michael A; Schroeder, Timm

2009-10-01

Cytokines are important regulators of cell fates with high clinical and commercial relevance. However, despite decades of intense academic and industrial research, it proved surprisingly difficult to describe the biological functions of cytokines in a precise and comprehensive manner. The exact analysis of cytokine biology is complicated by the fact that individual cytokines control many different cell fates and activate a multitude of intracellular signaling pathways. Moreover, although activating different molecular programs, different cytokines can be redundant in their biological effects. In addition, cytokines with different biological effects can activate overlapping signaling pathways. This prospect article will outline the necessity of continuous single cell biochemistry to unravel the biological functions of molecular cytokine signaling. It focuses on potentials and limitations of recent technical developments in fluorescent time-lapse imaging and single cell tracking allowing constant long-term observation of molecules and behavior of single cells. (c) 2009 Wiley-Liss, Inc.

Recent advances in food biopeptides: production, biological functionalities and therapeutic applications.

PubMed

Saadi, Sami; Saari, Nazamid; Anwar, Farooq; Abdul Hamid, Azizah; Ghazali, Hasanah Mohd

2015-01-01

The growing momentum of several common life-style diseases such as myocardial infarction, cardiovascular disorders, stroke, hypertension, diabetes, and atherosclerosis has become a serious global concern. Recent developments in the field of proteomics offering promising solutions to solving such health problems stimulates the uses of biopeptides as one of the therapeutic agents to alleviate disease-related risk factors. Functional peptides are typically produced from protein via enzymatic hydrolysis under in vitro or in vivo conditions using different kinds of proteolytic enzymes. An array of biological activities, including antioxidative, antihypertensive, antidiabetic and immunomodulating has been ascribed to different types of biopeptides derived from various food sources. In fact, biopeptides are nutritionally and functionally important for regulating some physiological functions in the body; however, these are yet to be extensively addressed with regard to their production through advance strategies, mechanisms of action and multiple biological functionalities. This review mainly focuses on recent biotechnological advances that are being made in the field of production in addition to covering the mode of action and biological activities, medicinal health functions and therapeutic applications of biopeptides. State-of-the-art strategies that can ameliorate the efficacy, bioavailability, and functionality of biopeptides along with their future prospects are likewise discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical synthetic biology: a mini-review.

PubMed

Chiarabelli, Cristiano; Stano, Pasquale; Luisi, Pier Luigi

2013-01-01

Chemical synthetic biology (CSB) is a branch of synthetic biology (SB) oriented toward the synthesis of chemical structures alternative to those present in nature. Whereas SB combines biology and engineering with the aim of synthesizing biological structures or life forms that do not exist in nature - often based on genome manipulation, CSB uses and assembles biological parts, synthetic or not, to create new and alternative structures. A short epistemological note will introduce the theoretical concepts related to these fields, whereas the text will be largely devoted to introduce and comment two main projects of CSB, carried out in our laboratory in the recent years. The "Never Born Biopolymers" project deals with the construction and the screening of RNA and peptide sequences that are not present in nature, whereas the "Minimal Cell" project focuses on the construction of semi-synthetic compartments (usually liposomes) containing the minimal and sufficient number of components to perform the basic function of a biological cell. These two topics are extremely important for both the general understanding of biology in terms of function, organization, and development, and for applied biotechnology.

Comparative genome analysis of PHB gene family reveals deep evolutionary origins and diverse gene function.

PubMed

Di, Chao; Xu, Wenying; Su, Zhen; Yuan, Joshua S

2010-10-07

PHB (Prohibitin) gene family is involved in a variety of functions important for different biological processes. PHB genes are ubiquitously present in divergent species from prokaryotes to eukaryotes. Human PHB genes have been found to be associated with various diseases. Recent studies by our group and others have shown diverse function of PHB genes in plants for development, senescence, defence, and others. Despite the importance of the PHB gene family, no comprehensive gene family analysis has been carried to evaluate the relatedness of PHB genes across different species. In order to better guide the gene function analysis and understand the evolution of the PHB gene family, we therefore carried out the comparative genome analysis of the PHB genes across different kingdoms. The relatedness, motif distribution, and intron/exon distribution all indicated that PHB genes is a relatively conserved gene family. The PHB genes can be classified into 5 classes and each class have a very deep evolutionary origin. The PHB genes within the class maintained the same motif patterns during the evolution. With Arabidopsis as the model species, we found that PHB gene intron/exon structure and domains are also conserved during the evolution. Despite being a conserved gene family, various gene duplication events led to the expansion of the PHB genes. Both segmental and tandem gene duplication were involved in Arabidopsis PHB gene family expansion. However, segmental duplication is predominant in Arabidopsis. Moreover, most of the duplicated genes experienced neofunctionalization. The results highlighted that PHB genes might be involved in important functions so that the duplicated genes are under the evolutionary pressure to derive new function. PHB gene family is a conserved gene family and accounts for diverse but important biological functions based on the similar molecular mechanisms. The highly diverse biological function indicated that more research needs to be carried out to dissect the PHB gene function. The conserved gene evolution indicated that the study in the model species can be translated to human and mammalian studies.

Paradoxical roles of dual oxidases in cancer biology.

PubMed

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

2017-09-01

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

Genomewide effects of peroxisome proliferator-activated receptor gamma in macrophages and dendritic cells--revealing complexity through systems biology.

PubMed

Cuaranta-Monroy, Ixchelt; Kiss, Mate; Simandi, Zoltan; Nagy, Laszlo

2015-09-01

Systems biology approaches have become indispensable tools in biomedical and basic research. These data integrating bioinformatic methods gained prominence after high-throughput technologies became available to investigate complex cellular processes, such as transcriptional regulation and protein-protein interactions, on a scale that had not been studied before. Immunology is one of the medical fields that systems biology impacted profoundly due to the plasticity of cell types involved and the accessibility of a wide range of experimental models. In this review, we summarize the most important recent genomewide studies exploring the function of peroxisome proliferator-activated receptor γ in macrophages and dendritic cells. PPARγ ChIP-seq experiments were performed in adipocytes derived from embryonic stem cells to complement the existing data sets and to provide comparators to macrophage data. Finally, lists of regulated genes generated from such experiments were analysed with bioinformatics and system biology approaches. We show that genomewide studies utilizing high-throughput data acquisition methods made it possible to gain deeper insights into the role of PPARγ in these immune cell types. We also demonstrate that analysis and visualization of data using network-based approaches can be used to identify novel genes and functions regulated by the receptor. The example of PPARγ in macrophages and dendritic cells highlights the crucial importance of systems biology approaches in establishing novel cellular functions for long-known signaling pathways. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Differences in the skeletal muscle transcriptome profile associated with extreme values of fatty acids content.

PubMed

Cesar, Aline S M; Regitano, Luciana C A; Poleti, Mirele D; Andrade, Sónia C S; Tizioto, Polyana C; Oliveira, Priscila S N; Felício, Andrezza M; do Nascimento, Michele L; Chaves, Amália S; Lanna, Dante P D; Tullio, Rymer R; Nassu, Renata T; Koltes, James E; Fritz-Waters, Eric; Mourão, Gerson B; Zerlotini-Neto, Adhemar; Reecy, James M; Coutinho, Luiz L

2016-11-22

Lipids are a class of molecules that play an important role in cellular structure and metabolism in all cell types. In the last few decades, it has been reported that long-chain fatty acids (FAs) are involved in several biological functions from transcriptional regulation to physiological processes. Several fatty acids have been both positively and negatively implicated in different biological processes in skeletal muscle and other tissues. To gain insight into biological processes associated with fatty acid content in skeletal muscle, the aim of the present study was to identify differentially expressed genes (DEGs) and functional pathways related to gene expression regulation associated with FA content in cattle. Skeletal muscle transcriptome analysis of 164 Nellore steers revealed no differentially expressed genes (DEGs, FDR 10%) for samples with extreme values for linoleic acid (LA) or stearic acid (SA), and only a few DEGs for eicosapentaenoic acid (EPA, 5 DEGs), docosahexaenoic acid (DHA, 4 DEGs) and palmitic acid (PA, 123 DEGs), while large numbers of DEGs were associated with oleic acid (OA, 1134 DEGs) and conjugated linoleic acid cis9 trans11 (CLA-c9t11, 872 DEGs). Functional annotation and functional enrichment from OA DEGs identified important genes, canonical pathways and upstream regulators such as SCD, PLIN5, UCP3, CPT1, CPT1B, oxidative phosphorylation mitochondrial dysfunction, PPARGC1A, and FOXO1. Two important genes associated with lipid metabolism, gene expression and cancer were identified as DEGs between animals with high and low CLA-c9t11, specifically, epidermal growth factor receptor (EGFR) and RNPS. Only two out of seven classes of molecules of FA studied were associated with large changes in the expression profile of skeletal muscle. OA and CLA-c9t11 content had significant effects on the expression level of genes related to important biological processes associated with oxidative phosphorylation, and cell growth, survival, and migration. These results contribute to our understanding of how some FAs modulate metabolism and may have protective health function.

Biological roles and functional mechanisms of arenavirus Z protein in viral replication.

PubMed

Wang, Jialong; Danzy, Shamika; Kumar, Naveen; Ly, Hinh; Liang, Yuying

2012-09-01

Arenaviruses can cause severe hemorrhagic fever diseases in humans, with limited prophylactic or therapeutic measures. A small RING-domain viral protein Z has been shown to mediate the formation of virus-like particles and to inhibit viral RNA synthesis, although its biological roles in an infectious viral life cycle have not been directly addressed. By taking advantage of the available reverse genetics system for a model arenavirus, Pichinde virus (PICV), we provide the direct evidence for the essential biological roles of the Z protein's conserved residues, including the G2 myristylation site, the conserved C and H residues of RING domain, and the poorly characterized C-terminal L79 and P80 residues. Dicodon substitutions within the late (L) domain (PSAPPYEP) of the PICV Z protein, although producing viable mutant viruses, have significantly reduced virus growth, a finding suggestive of an important role for the intact L domain in viral replication. Further structure-function analyses of both PICV and Lassa fever virus Z proteins suggest that arenavirus Z proteins have similar molecular mechanisms in mediating their multiple functions, with some interesting variations, such as the role of the G2 residue in blocking viral RNA synthesis. In summary, our studies have characterized the biological roles of the Z protein in an infectious arenavirus system and have shed important light on the distinct functions of its domains in virus budding and viral RNA regulation, the knowledge of which may lead to the development of novel antiviral drugs.

Development and application of automated systems for plasmid-based functional proteomics to improve syntheitc biology of engineered industrial microbes for high level expression of proteases for biofertilizer production

USDA-ARS?s Scientific Manuscript database

In addition to microarray technology, which provides a robust method to study protein function in a rapid, economical, and proteome-wide fashion, plasmid-based functional proteomics is an important technology for rapidly obtaining large quantities of protein and determining protein function across a...

Exploiting Allee effects for managing biological invasions

Treesearch

Patrick C. Tobin; Ludek Berec; Andrew M. Liebhold

2011-01-01

Biological invasions are a global and increasing threat to the function and diversity of ecosystems. Allee effects (positive density dependence) have been shown to play an important role in the establishment and spread of non-native species. Although Allee effects can be considered a bane in conservation efforts, they can be a benefit in attempts to manage non-native...

10 years for the Journal of Bioinformatics and Computational Biology (2003-2013) -- a retrospective.

PubMed

Eisenhaber, Frank; Sherman, Westley Arthur

2014-06-01

The Journal of Bioinformatics and Computational Biology (JBCB) started publishing scientific articles in 2003. It has established itself as home for solid research articles in the field (~ 60 per year) that are surprisingly well cited. JBCB has an important function as alternative publishing channel in addition to other, bigger journals.

Challenges and complexity of functionality evaluation of flavan-3-ol derivatives.

PubMed

Saito, Akiko

2017-06-01

Flavan-3-ol derivatives are common plant-derived bioactive compounds. In particular, (-)-epigallocatechin-3-O-gallate shows various moderate biological activities without severe toxicity, and its health-promoting effects have been widely studied because it is a main ingredient in green tea and is commercially available at low cost. Although various biologically active flavan-3-ol derivatives are present as minor constituents in plants as well as in green tea, their biological activities have yet to be revealed, mainly due to their relative unavailability. Here, I outline the major factors contributing to the complexity of functionality studies of flavan-3-ol derivatives, including proanthocyanidins and oligomeric flavan-3-ols. I emphasize the importance of conducting structure-activity relationship studies using synthesized flavan-3-ol derivatives that are difficult to obtain from plant extracts in pure form to overcome this challenge. Further discovery of these minor constituents showing strong biological activities is expected to produce useful information for the development of functional health foods.

How cancer cells dictate their microenvironment: present roles of extracellular vesicles.

PubMed

Naito, Yutaka; Yoshioka, Yusuke; Yamamoto, Yusuke; Ochiya, Takahiro

2017-02-01

Intercellular communication plays an important role in cancer initiation and progression through secretory molecules, including growth factors and cytokines. Recent advances have revealed that small membrane vesicles, termed extracellular vesicles (EVs), served as a regulatory agent in the intercellular communication of cancer. EVs enable the transfer of functional molecules, including proteins, mRNA and microRNAs (miRNAs), into recipient cells. Cancer cells utilize EVs to dictate the unique phenotype of surrounding cells, thereby promoting cancer progression. Against such "education" by cancer cells, non-tumoral cells suppress cancer initiation and progression via EVs. Therefore, researchers consider EVs to be important cues to clarify the molecular mechanisms of cancer biology. Understanding the functions of EVs in cancer progression is an important aspect of cancer biology that has not been previously elucidated. In this review, we summarize experimental data that indicate the pivotal roles of EVs in cancer progression.

Functional comparison of microarray data across multiple platforms using the method of percentage of overlapping functions.

PubMed

Li, Zhiguang; Kwekel, Joshua C; Chen, Tao

2012-01-01

Functional comparison across microarray platforms is used to assess the comparability or similarity of the biological relevance associated with the gene expression data generated by multiple microarray platforms. Comparisons at the functional level are very important considering that the ultimate purpose of microarray technology is to determine the biological meaning behind the gene expression changes under a specific condition, not just to generate a list of genes. Herein, we present a method named percentage of overlapping functions (POF) and illustrate how it is used to perform the functional comparison of microarray data generated across multiple platforms. This method facilitates the determination of functional differences or similarities in microarray data generated from multiple array platforms across all the functions that are presented on these platforms. This method can also be used to compare the functional differences or similarities between experiments, projects, or laboratories.

The human mouth: oral functions in a social complexity perspective.

PubMed

Eriksen, Harald M; Dimitrov, Vladimir

2003-06-01

In the dental and medical literature, the mouth and oral functions are usually presented in a biomedical context. However, there may be a need for a broader perspective if we are to appreciate the importance of the human mouth as an organ with diverse functions. The paradigm of complexity appears to be of relevance in our understanding the social and psychological characteristics of the human mouth in addition to its biological functions. Examples such as the pleasures of taste, social aspects of eating, the importance of linguistics and communication are illustrations of some of the social and psychological aspects of oral functions. Professional knowledge related to such issues is important in our understanding the patient's priorities and in performing the relevant diagnosis and treatment planning.

TOXICOGENOMICS AS A TOOL TO ASSESS EXPOSURE OF FISH TO ENVIRONMENTAL POLLUTANTS

EPA Science Inventory

Molecular biological techniques such as gene arrays and quantitative real-time PCR are becoming important tools to study alterations in normal gene expression in fish and other wildlife exposed to such pollutants as endocrine disrupting chemicals (EDCs). An important function fo...

Building robust functionality in synthetic circuits using engineered feedback regulation.

PubMed

Chen, Susan; Harrigan, Patrick; Heineike, Benjamin; Stewart-Ornstein, Jacob; El-Samad, Hana

2013-08-01

The ability to engineer novel functionality within cells, to quantitatively control cellular circuits, and to manipulate the behaviors of populations, has many important applications in biotechnology and biomedicine. These applications are only beginning to be explored. In this review, we advocate the use of feedback control as an essential strategy for the engineering of robust homeostatic control of biological circuits and cellular populations. We also describe recent works where feedback control, implemented in silico or with biological components, was successfully employed for this purpose. Copyright © 2013 Elsevier Ltd. All rights reserved.

Functionalized gold nanoparticle supported sensory mechanisms applied in detection of chemical and biological threat agents: a review.

PubMed

Upadhyayula, Venkata K K

2012-02-17

There is a great necessity for development of novel sensory concepts supportive of smart sensing capabilities in defense and homeland security applications for detection of chemical and biological threat agents. A smart sensor is a detection device that can exhibit important features such as speed, sensitivity, selectivity, portability, and more importantly, simplicity in identifying a target analyte. Emerging nanomaterial based sensors, particularly those developed by utilizing functionalized gold nanoparticles (GNPs) as a sensing component potentially offer many desirable features needed for threat agent detection. The sensitiveness of physical properties expressed by GNPs, e.g. color, surface plasmon resonance, electrical conductivity and binding affinity are significantly enhanced when they are subjected to functionalization with an appropriate metal, organic or biomolecular functional groups. This sensitive nature of functionalized GNPs can be potentially exploited in the design of threat agent detection devices with smart sensing capabilities. In the presence of a target analyte (i.e., a chemical or biological threat agent) a change proportional to concentration of the analyte is observed, which can be measured either by colorimetric, fluorimetric, electrochemical or spectroscopic means. This article provides a review of how functionally modified gold colloids are applied in the detection of a broad range of threat agents, including radioactive substances, explosive compounds, chemical warfare agents, biotoxins, and biothreat pathogens through any of the four sensory means mentioned previously. Copyright © 2011 Elsevier B.V. All rights reserved.

Functionalized C-Glycoside Ketohydrazones: Carbohydrate Derivatization that Retains the Ring Integrity of the Terminal Reducing Sugar

USDA-ARS?s Scientific Manuscript database

Glycosylation often mediates important biological processes through the interaction of carbohydrates with complementary proteins. Most chemical tools for the functional analysis of glycans are highly dependent upon various linkage chemistries that involve the reducing-terminus of carbohydrates. Ho...

Tetrazine ligation for chemical proteomics.

PubMed

Kang, Kyungtae; Park, Jongmin; Kim, Eunha

2016-01-01

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

Long Non-coding RNAs and Their Biological Roles in Plants

PubMed Central

Liu, Xue; Hao, Lili; Li, Dayong; Zhu, Lihuang; Hu, Songnian

2015-01-01

With the development of genomics and bioinformatics, especially the extensive applications of high-throughput sequencing technology, more transcriptional units with little or no protein-coding potential have been discovered. Such RNA molecules are called non-protein-coding RNAs (npcRNAs or ncRNAs). Among them, long npcRNAs or ncRNAs (lnpcRNAs or lncRNAs) represent diverse classes of transcripts longer than 200 nucleotides. In recent years, the lncRNAs have been considered as important regulators in many essential biological processes. In plants, although a large number of lncRNA transcripts have been predicted and identified in few species, our current knowledge of their biological functions is still limited. Here, we have summarized recent studies on their identification, characteristics, classification, bioinformatics, resources, and current exploration of their biological functions in plants. PMID:25936895

Carbohydrates--the renewable raw materials of high biotechnological value.

PubMed

Ramesh, Honnavally P F; Tharanathan, Rudrapatnam N

2003-01-01

Carbohydrates are the potential biomolecules derived from nature. Their molecular diversity has led to a bewildering variety of species, structures and characteristics all performing a large array of functions of great significance. Biologically they are vital as message (immunological) carriers, physiologically they are useful as energy (nutritional) reserves, and technologically they are needed for altering the texture and consistency (functional) of foods. Recent advances in glycobiology have opened up a new understanding of the role of sugars in biology and medicine. Noncellulosic beta-(1-3)-linked D-glucans, a group of polysaccharides found as constituents of fungi, algae, and higher plants, exhibit many interesting properties, depending on their molecular conformation. They are excellent 'biological response modifiers' and show significant immunomodulatory activities. They elicit a variety of host defense biological responses, for example, potent antitumor activity. On the other hand, the mixed-linkage ((1-3/1-4)-beta-linked) glucans are important constituents of cereal cell walls, where they perform properties of physiological importance, such as water holding capacity, porosity, and plasticity, which are useful at different stages of growth/development of plants. Of late, carbohydrate-based therapeutics are becoming the promise against many chronic diseases of today and tomorrow. Some of the characteristic features, structural attributes, functional significance, and applications of a selected few carbohydrate species are the subject matter of this review.

Force spectroscopy studies on protein-ligand interactions: a single protein mechanics perspective.

PubMed

Hu, Xiaotang; Li, Hongbin

2014-10-01

Protein-ligand interactions are ubiquitous and play important roles in almost every biological process. The direct elucidation of the thermodynamic, structural and functional consequences of protein-ligand interactions is thus of critical importance to decipher the mechanism underlying these biological processes. A toolbox containing a variety of powerful techniques has been developed to quantitatively study protein-ligand interactions in vitro as well as in living systems. The development of atomic force microscopy-based single molecule force spectroscopy techniques has expanded this toolbox and made it possible to directly probe the mechanical consequence of ligand binding on proteins. Many recent experiments have revealed how ligand binding affects the mechanical stability and mechanical unfolding dynamics of proteins, and provided mechanistic understanding on these effects. The enhancement effect of mechanical stability by ligand binding has been used to help tune the mechanical stability of proteins in a rational manner and develop novel functional binding assays for protein-ligand interactions. Single molecule force spectroscopy studies have started to shed new lights on the structural and functional consequence of ligand binding on proteins that bear force under their biological settings. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Role of p21-activated kinases in cardiovascular development and function.

PubMed

Kelly, Mollie L; Astsaturov, Artyom; Chernoff, Jonathan

2013-11-01

p21-activated kinases (Paks) are a group of six serine/threonine kinases (Pak1-6) that are involved in a variety of biological processes. Recently, Paks, more specifically Pak1, -2, and -4, have been shown to play important roles in cardiovascular development and function in a range of model organisms including zebrafish and mice. These functions include proper morphogenesis and conductance of the heart, cardiac contractility, and development and integrity of the vasculature. The mechanisms underlying these effects are not fully known, but they likely differ among the various Pak isoforms and include both kinase-dependent and -independent functions. In this review, we discuss aspects of Pak function relevant to cardiovascular biology as well as potential therapeutic implications of small-molecule Pak inhibitors in cardiovascular disease.

Synthetic biology: Novel approaches for microbiology.

PubMed

Padilla-Vaca, Felipe; Anaya-Velázquez, Fernando; Franco, Bernardo

2015-06-01

In the past twenty years, molecular genetics has created powerful tools for genetic manipulation of living organisms. Whole genome sequencing has provided necessary information to assess knowledge on gene function and protein networks. In addition, new tools permit to modify organisms to perform desired tasks. Gene function analysis is speed up by novel approaches that couple both high throughput data generation and mining. Synthetic biology is an emerging field that uses tools for generating novel gene networks, whole genome synthesis and engineering. New applications in biotechnological, pharmaceutical and biomedical research are envisioned for synthetic biology. In recent years these new strategies have opened up the possibilities to study gene and genome editing, creation of novel tools for functional studies in virus, parasites and pathogenic bacteria. There is also the possibility to re-design organisms to generate vaccine subunits or produce new pharmaceuticals to combat multi-drug resistant pathogens. In this review we provide our opinion on the applicability of synthetic biology strategies for functional studies of pathogenic organisms and some applications such as genome editing and gene network studies to further comprehend virulence factors and determinants in pathogenic organisms. We also discuss what we consider important ethical issues for this field of molecular biology, especially for potential misuse of the new technologies. Copyright© by the Spanish Society for Microbiology and Institute for Catalan Studies.

Lateral organization of biological membranes: role of long-range interactions.

PubMed

Duneau, Jean-Pierre; Sturgis, James N

2013-12-01

The lateral organization of biological membranes is of great importance in many biological processes, both for the formation of specific structures such as super-complexes and for function as observed in signal transduction systems. Over the last years, AFM studies, particularly of bacterial photosynthetic membranes, have revealed that certain proteins are able to segregate into functional domains with a specific organization. Furthermore, the extended non-random nature of the organization has been suggested to be important for the energy and redox transport properties of these specialized membranes. In the work reported here, using a coarse-grained Monte Carlo approach, we have investigated the nature of interaction potentials able to drive the formation and segregation of specialized membrane domains from the rest of the membrane and furthermore how the internal organization of the segregated domains can be modulated by the interaction potentials. These simulations show that long-range interactions are necessary to allow formation of membrane domains of realistic structure. We suggest that such possibly non-specific interactions may be of great importance in the lateral organization of biological membranes in general and in photosynthetic systems in particular. Finally, we consider the possible molecular origins of such interactions and suggest a fundamental role for lipid-mediated interactions in driving the formation of specialized photosynthetic membrane domains. We call these lipid-mediated interactions a 'lipophobic effect.'

Intrinsic disorder in spondins and some of their interacting partners

PubMed Central

Alowolodu, Oluwole; Johnson, Gbemisola; Addou, Iqbal; Zhdanova, Irina V.; Uversky, Vladimir N.

2016-01-01

ABSTRACT Spondins, which are proteins that inhibit and promote adherence of embryonic cells so as to aid axonal growth are part of the thrombospondin-1 family. Spondins function in several important biological processes, such as apoptosis, angiogenesis, etc. Spondins constitute a thrombospondin subfamily that includes F-spondin, a protein that interacts with Aβ precursor protein and inhibits its proteolytic processing; R-spondin, a 4-membered group of proteins that regulates Wnt pathway and have other functions, such as regulation of kidney proliferation, induction of epithelial proliferation, the tumor suppressant action; M-spondin that mediates mechanical linkage between the muscles and apodemes; and the SCO-spondin, a protein important for neuronal development. In this study, we investigated intrinsic disorder status of human spondins and their interacting partners, such as members of the LRP family, LGR family, Frizzled family, and several other binding partners in order to establish the existence and importance of disordered regions in spondins and their interacting partners by conducting a detailed analysis of their sequences, finding disordered regions, and establishing a correlation between their structure and biological functions. PMID:28232900

Social relationships and social support among post-war youth in Northern Uganda.

PubMed

De Nutte, Leen; Okello, James; Derluyn, Ilse

2017-08-01

Although social relationships and social support are salient factors for post-war adolescents' psychosocial coping and adjustment, there is only limited information regarding war-affected adolescents' views on social support and the relationships within which social support is provided. This study therefore explored both elements among a clinical sample of 20 adolescents living in post-war Northern Uganda. Following Braun and Clarke's thematic analysis, we found a prominent role of the biological mother and other primary biological family members in the upbringing of our participants. Spiritual and material support were perceived to be the most important type of support, respectively, while the adolescents were growing up and in their current lives. These findings provide support for the perception that caregiving systems are adaptable to particular sociocultural contexts. Further, the importance of particular functions of social support could signify a potentially selective buffering effect of these functions in adverse contexts. Because of the importance of the primary biological family and the salient role of parent-child relationships in the face of adversity, future research needs to focus on this particular kind of social relationship in contexts of prolonged collective violence. © 2015 International Union of Psychological Science.

What makes the desert bloom? Contribution of dust and crusts to soil fertility on the Colorado Plateau

Treesearch

Jayne Belnap; Richard Reynolds; Marith Reheis; Susan L. Phillips

2001-01-01

Eolian dust (windblown silt and clay) and biological soil crusts are both important to ecosystem functioning of arid lands. Dust furnishes essential nutrients, influences hydrology, contributes to soil formation, and renders surfaces vulnerable to erosion. Biological soil crusts contribute directly to soil fertility by fixing carbon and nitrogen, and indirectly by...

ClusterViz: A Cytoscape APP for Cluster Analysis of Biological Network.

PubMed

Wang, Jianxin; Zhong, Jiancheng; Chen, Gang; Li, Min; Wu, Fang-xiang; Pan, Yi

2015-01-01

Cluster analysis of biological networks is one of the most important approaches for identifying functional modules and predicting protein functions. Furthermore, visualization of clustering results is crucial to uncover the structure of biological networks. In this paper, ClusterViz, an APP of Cytoscape 3 for cluster analysis and visualization, has been developed. In order to reduce complexity and enable extendibility for ClusterViz, we designed the architecture of ClusterViz based on the framework of Open Services Gateway Initiative. According to the architecture, the implementation of ClusterViz is partitioned into three modules including interface of ClusterViz, clustering algorithms and visualization and export. ClusterViz fascinates the comparison of the results of different algorithms to do further related analysis. Three commonly used clustering algorithms, FAG-EC, EAGLE and MCODE, are included in the current version. Due to adopting the abstract interface of algorithms in module of the clustering algorithms, more clustering algorithms can be included for the future use. To illustrate usability of ClusterViz, we provided three examples with detailed steps from the important scientific articles, which show that our tool has helped several research teams do their research work on the mechanism of the biological networks.

Bench to bedside molecular functional imaging in translational cancer medicine: to image or to imagine?

PubMed

Mahajan, A; Goh, V; Basu, S; Vaish, R; Weeks, A J; Thakur, M H; Cook, G J

2015-10-01

Ongoing research on malignant and normal cell biology has substantially enhanced the understanding of the biology of cancer and carcinogenesis. This has led to the development of methods to image the evolution of cancer, target specific biological molecules, and study the anti-tumour effects of novel therapeutic agents. At the same time, there has been a paradigm shift in the field of oncological imaging from purely structural or functional imaging to combined multimodal structure-function approaches that enable the assessment of malignancy from all aspects (including molecular and functional level) in a single examination. The evolving molecular functional imaging using specific molecular targets (especially with combined positron-emission tomography [PET] computed tomography [CT] using 2- [(18)F]-fluoro-2-deoxy-D-glucose [FDG] and other novel PET tracers) has great potential in translational research, giving specific quantitative information with regard to tumour activity, and has been of pivotal importance in diagnoses and therapy tailoring. Furthermore, molecular functional imaging has taken a key place in the present era of translational cancer research, producing an important tool to study and evolve newer receptor-targeted therapies, gene therapies, and in cancer stem cell research, which could form the basis to translate these agents into clinical practice, popularly termed "theranostics". Targeted molecular imaging needs to be developed in close association with biotechnology, information technology, and basic translational scientists for its best utility. This article reviews the current role of molecular functional imaging as one of the main pillars of translational research. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Identification, RNAi Knockdown and Functional Analysis of an Ejaculate Protein that Mediates a Postmating, Prezgotic Phenotype in a cricket

USDA-ARS?s Scientific Manuscript database

Male ejaculate proteins, including both sperm and seminal fluid proteins, play an important role in mediating reproductive biology. The function of ejaculate proteins can include enabling sperm-egg interactions, enhancing sperm storage, mediating female attractiveness, and even regulating female lif...

Flooding facility helps scientists examine the ecophysiology of floodplain species used in bottomland hardwood restorations

Treesearch

Brian R. Lockhart; Emile S. Gardiner; Theodore D. Leininger; Kristina F. Connor; Paul B. Hamel; Nathan M. Schiff; A. Dan Wilson; Margaret S. Devall

2006-01-01

Bottomland hardwood ecosystems, important for their unique functions and values, have experienced considerable degradation since European settlement through deforestation, development, and drainage. Currently, considerable effort is underway to restore ecological functions on degraded bottomland sites. Restoration requires a better understanding of the biological...

Evaluation of soil processing conditions on mineralizable C and N across a textural gradient

USDA-ARS?s Scientific Manuscript database

Soil biological activity is an important component of a well-functioning soil. Methodologies for estimating this process in soil vary due to a variety of theoretical, functional, and expediency considerations. We tested the effects of soil processing (sieve size), water delivery method (from top a...

Connecting soil microbial communities to soil functioning and soil health

USDA-ARS?s Scientific Manuscript database

One of the most important functions soils perform, is the capacity to buffer anthropogenic disturbances to sustain productivity while improving water and air quality. At the core of a healthy soil is a biological active and diverse community that provides internal nutrient cycling and is resilient t...

A guide to large-scale RNA sample preparation.

PubMed

Baronti, Lorenzo; Karlsson, Hampus; Marušič, Maja; Petzold, Katja

2018-05-01

RNA is becoming more important as an increasing number of functions, both regulatory and enzymatic, are being discovered on a daily basis. As the RNA boom has just begun, most techniques are still in development and changes occur frequently. To understand RNA functions, revealing the structure of RNA is of utmost importance, which requires sample preparation. We review the latest methods to produce and purify a variation of RNA molecules for different purposes with the main focus on structural biology and biophysics. We present a guide aimed at identifying the most suitable method for your RNA and your biological question and highlighting the advantages of different methods. Graphical abstract In this review we present different methods for large-scale production and purification of RNAs for structural and biophysical studies.

Epilepsy, language, and social skills.

PubMed

Caplan, Rochelle

2017-10-04

Language and social skills are essential for intrapersonal and interpersonal functioning and quality of life. Since epilepsy impacts these important domains of individuals' functioning, understanding the psychosocial and biological factors involved in the relationship among epilepsy, language, and social skills has important theoretical and clinical implications. This review first describes the psychosocial and biological factors involved in the association between language and social behavior in children and in adults and their relevance for epilepsy. It reviews the findings of studies of social skills and the few studies conducted on the inter-relationship of language and social skills in pediatric and adult epilepsy. The paper concludes with suggested future research and clinical directions that will enhance early identification and treatment of epilepsy patients at risk for impaired language and social skills. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-11-01

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

Telomere biology in aging and cancer: early history and perspectives.

PubMed

Hayashi, Makoto T

2018-01-20

The ends of eukaryotic linear chromosomes are protected from undesired enzymatic activities by a nucleoprotein complex called the telomere. Expanding evidence indicates that telomeres have central functions in human aging and tumorigenesis. While it is undoubtedly important to follow current advances in telomere biology, it is also fruitful to be well informed in seminal historical studies for a comprehensive understanding of telomere biology, and for the anticipation of future directions. With this in mind, I here summarize the early history of telomere biology and current advances in the field, mostly focusing on mammalian studies relevant to aging and cancer.

Not just a theory--the utility of mathematical models in evolutionary biology.

PubMed

Servedio, Maria R; Brandvain, Yaniv; Dhole, Sumit; Fitzpatrick, Courtney L; Goldberg, Emma E; Stern, Caitlin A; Van Cleve, Jeremy; Yeh, D Justin

2014-12-01

Progress in science often begins with verbal hypotheses meant to explain why certain biological phenomena exist. An important purpose of mathematical models in evolutionary research, as in many other fields, is to act as “proof-of-concept” tests of the logic in verbal explanations, paralleling the way in which empirical data are used to test hypotheses. Because not all subfields of biology use mathematics for this purpose, misunderstandings of the function of proof-of-concept modeling are common. In the hope of facilitating communication, we discuss the role of proof-of-concept modeling in evolutionary biology.

Functional network in posttranslational modifications: Glyco-Net in Glycoconjugate Data Bank.

PubMed

Miura, Nobuaki; Okada, Takuya; Murayama, Daisuke; Hirose, Kazuko; Sato, Taku; Hashimoto, Ryo; Fukushima, Nobuhiro

2015-01-01

Elucidating pathways related to posttranslational modifications (PTMs) such as glycosylation is of growing importance in post-genome science and technology. Graphical networks describing the relationships among glycan-related molecules, including genes, proteins, lipids, and various biological events, are considered extremely valuable and convenient tools for the systematic investigation of PTMs. Glyco-Net (http://bibi.sci.hokudai.ac.jp/functions/) can dynamically make network figures among various biological molecules and biological events. A certain molecule or event is expressed with a node, and the relationship between the molecule and the event is indicated by arrows in the network figures. In this chapter, we mention the features and current status of the Glyco-Net and a simple example of the search with the Glyco-Net.

Biological pathways involved in the development of inflammatory bowel disease.

PubMed

Zemljic, Mateja; Pejkovic, Bozena; Krajnc, Ivan; Lipovsek, Saska

2014-10-01

Apoptosis, autophagy and necrosis are three distinct functional types of the mammalian cell death network. All of them are characterized by a number of cell's morphological changes. The inappropriate induction of cell death is involved in the pathogenesis of a number of diseases.Pathogenesis of inflammatory bowel diseases (ulcerative colitis, Crohn's disease) includes an abnormal immunological response to disturbed intestinal microflora. One of the most important reason in pathogenesis of chronic inflammatory disease and subsequent multiple organ pathology is a barrier function of the gut, regulating cellular viability. Recent findings have begun to explain the mechanisms by which intestinal epithelial cells are able to survive in such an environment and how loss of normal regulatory processes may lead to inflammatory bowel disease (IBD).This review focuses on the regulation of biological pathways in development and homeostasis in IBD. Better understanding of the physiological functions of biological pathways and their influence on inflammation, immunity, and barrier function will simplify our expertice of homeostasis in the gastrointestinal tract and in upgrading diagnosis and treatment.

A Novel Characterization of Amalgamated Networks in Natural Systems

PubMed Central

Barranca, Victor J.; Zhou, Douglas; Cai, David

2015-01-01

Densely-connected networks are prominent among natural systems, exhibiting structural characteristics often optimized for biological function. To reveal such features in highly-connected networks, we introduce a new network characterization determined by a decomposition of network-connectivity into low-rank and sparse components. Based on these components, we discover a new class of networks we define as amalgamated networks, which exhibit large functional groups and dense connectivity. Analyzing recent experimental findings on cerebral cortex, food-web, and gene regulatory networks, we establish the unique importance of amalgamated networks in fostering biologically advantageous properties, including rapid communication among nodes, structural stability under attacks, and separation of network activity into distinct functional modules. We further observe that our network characterization is scalable with network size and connectivity, thereby identifying robust features significant to diverse physical systems, which are typically undetectable by conventional characterizations of connectivity. We expect that studying the amalgamation properties of biological networks may offer new insights into understanding their structure-function relationships. PMID:26035066

Long Noncoding RNAs: Past, Present, and Future

PubMed Central

Kung, Johnny T. Y.; Colognori, David; Lee, Jeannie T.

2013-01-01

Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years as a potentially new and crucial layer of biological regulation. lncRNAs of all kinds have been implicated in a range of developmental processes and diseases, but knowledge of the mechanisms by which they act is still surprisingly limited, and claims that almost the entirety of the mammalian genome is transcribed into functional noncoding transcripts remain controversial. At the same time, a small number of well-studied lncRNAs have given us important clues about the biology of these molecules, and a few key functional and mechanistic themes have begun to emerge, although the robustness of these models and classification schemes remains to be seen. Here, we review the current state of knowledge of the lncRNA field, discussing what is known about the genomic contexts, biological functions, and mechanisms of action of lncRNAs. We also reflect on how the recent interest in lncRNAs is deeply rooted in biology’s longstanding concern with the evolution and function of genomes. PMID:23463798

Ecosystem function in waste stabilisation ponds: Improving water quality through a better understanding of biophysical coupling

NASA Astrophysics Data System (ADS)

Ghadouani, Anas; Reichwaldt, Elke S.; Coggins, Liah X.; Ivey, Gregory N.; Ghisalberti, Marco; Zhou, Wenxu; Laurion, Isabelle; Chua, Andrew

2014-05-01

Wastewater stabilisation ponds (WSPs) are highly productive systems designed to treat wastewater using only natural biological and chemical processes. Phytoplankton, microbial communities and hydraulics play important roles for ecosystem functionality of these pond systems. Although WSPs have been used for many decades, they are still considered as 'black box' systems as very little is known about the fundamental ecological processes which occur within them. However, a better understanding of how these highly productive ecosystems function is particularly important for hydrological processes, as treated wastewater is commonly discharged into streams, rivers, and oceans, and subject to strict water quality guidelines. WSPs are known to operate at different levels of efficiency, and treatment efficiency of WSPs is dependent on physical (flow characteristics and sludge accumulation and distribution) and biological (microbial and phytoplankton communities) characteristics. Thus, it is important to gain a better understanding of the role and influence of pond hydraulics and vital microbial communities on pond performance and WSP functional stability. The main aim of this study is to investigate the processes leading to differences in treatment performance of WSPs. This study uses a novel and innovative approach to understand these factors by combining flow cytometry and metabolomics to investigate various biochemical characteristics, including the metabolite composition and microbial community within WSPs. The results of these analyses will then be combined with results from the characterisation of pond hydrodynamics and hydraulic performance, which will be performed using advanced hydrodynamic modelling and advanced sludge profiling technology. By understanding how hydrodynamic and biological processes influence each other and ecosystem function and stability in WSPs, we will be able to propose ways to improve the quality of the treatment using natural processes, with less reliance on chemical treatment. This will in turn contribute to the reduction in the cost of operation, but more importantly reduce the impact on the environment (i.e., discharge, GHGs), and increase water quality and the potential for water reuse worldwide.

From Sequence and Forces to Structure, Function and Evolution of Intrinsically Disordered Proteins

PubMed Central

Forman-Kay, Julie D.; Mittag, Tanja

2015-01-01

Intrinsically disordered proteins (IDPs), which lack persistent structure, are a challenge to structural biology due to the inapplicability of standard methods for characterization of folded proteins as well as their deviation from the dominant structure/function paradigm. Their widespread presence and involvement in biological function, however, has spurred the growing acceptance of the importance of IDPs and the development of new tools for studying their structure, dynamics and function. The interplay of folded and disordered domains or regions for function and the existence of a continuum of protein states with respect to conformational energetics, motional timescales and compactness is shaping a unified understanding of structure-dynamics-disorder/function relationships. On the 20th anniversary of this journal, Structure, we provide a historical perspective on the investigation of IDPs and summarize the sequence features and physical forces that underlie their unique structural, functional and evolutionary properties. PMID:24010708

From sequence and forces to structure, function, and evolution of intrinsically disordered proteins.

PubMed

Forman-Kay, Julie D; Mittag, Tanja

2013-09-03

Intrinsically disordered proteins (IDPs), which lack persistent structure, are a challenge to structural biology due to the inapplicability of standard methods for characterization of folded proteins as well as their deviation from the dominant structure/function paradigm. Their widespread presence and involvement in biological function, however, has spurred the growing acceptance of the importance of IDPs and the development of new tools for studying their structure, dynamics, and function. The interplay of folded and disordered domains or regions for function and the existence of a continuum of protein states with respect to conformational energetics, motional timescales, and compactness are shaping a unified understanding of structure-dynamics-disorder/function relationships. In the 20(th) anniversary of Structure, we provide a historical perspective on the investigation of IDPs and summarize the sequence features and physical forces that underlie their unique structural, functional, and evolutionary properties. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bioelectronic Sensors and Devices

NASA Astrophysics Data System (ADS)

Reed, Mark

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

From pericytes to perivascular tumours: correlation between pathology, stem cell biology, and tissue engineering.

PubMed

Mravic, Marco; Asatrian, Greg; Soo, Chia; Lugassy, Claire; Barnhill, Raymond L; Dry, Sarah M; Peault, Bruno; James, Aaron W

2014-09-01

Pericytes were once thought only to aid in angiogenesis and blood pressure control. Gradually, the known functions of pericytes and other perivascular stem cells (PSC) have broadly increased. The following review article will summarize the known functions and importance of pericytes across disciplines of pathology, stem cell biology, and tissue engineering. A literature review was performed for studies examining the importance of pericytes in pathology, stem cell biology, and tissue engineering. The importance of pericytes most prominently includes the identification of the perivascular identity of mesenchymal stem cells (or MSC). Now, pericytes and other PSC are known to display surface markers and multilineage differentiation potential of MSC. Accordingly, interest in the purification and use of PSC for mesenchymal tissue formation and regeneration has increased. Significant demonstration of in vivo efficacy in bone and muscle regeneration has been made in laboratory animals. Contemporaneously with the uncovering of an MSC identity for pericytes, investigators in tumour biology have found biologically relevant roles for pericytes in tumor formation, lymphovascular invasion, and perivascular tumor spread. As well, the contribution of pericytes to perivascular tumors has been examined (and debated), including glomus tumour, myopericytoma and solitary fibrous tumour/hemangiopericytoma. In addition, an expanding recognition of pericyte mimicry and perivascular tumour invasion has occurred, encompassing common malignancies of the brain and skin. In summary, pericytes have a wide range of roles in health and disease. Pericytes are being increasingly studied for their role in tumour formation, growth and invasion. Likewise, the application of pericytes/PSC for mesenchymal tissue engineering is an expanding field of interest.

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

NASA Astrophysics Data System (ADS)

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

2014-12-01

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

Systems biology-based approaches toward understanding drought tolerance in food crops.

PubMed

Jogaiah, Sudisha; Govind, Sharathchandra Ramsandra; Tran, Lam-Son Phan

2013-03-01

Economically important crops, such as maize, wheat, rice, barley, and other food crops are affected by even small changes in water potential at important growth stages. Developing a comprehensive understanding of host response to drought requires a global view of the complex mechanisms involved. Research on drought tolerance has generally been conducted using discipline-specific approaches. However, plant stress response is complex and interlinked to a point where discipline-specific approaches do not give a complete global analysis of all the interlinked mechanisms. Systems biology perspective is needed to understand genome-scale networks required for building long-lasting drought resistance. Network maps have been constructed by integrating multiple functional genomics data with both model plants, such as Arabidopsis thaliana, Lotus japonicus, and Medicago truncatula, and various food crops, such as rice and soybean. Useful functional genomics data have been obtained from genome-wide comparative transcriptome and proteome analyses of drought responses from different crops. This integrative approach used by many groups has led to identification of commonly regulated signaling pathways and genes following exposure to drought. Combination of functional genomics and systems biology is very useful for comparative analysis of other food crops and has the ability to develop stable food systems worldwide. In addition, studying desiccation tolerance in resurrection plants will unravel how combination of molecular genetic and metabolic processes interacts to produce a resurrection phenotype. Systems biology-based approaches have helped in understanding how these individual factors and mechanisms (biochemical, molecular, and metabolic) "interact" spatially and temporally. Signaling network maps of such interactions are needed that can be used to design better engineering strategies for improving drought tolerance of important crop species.

Yeast Genomics for Bread, Beer, Biology, Bucks and Breath

NASA Astrophysics Data System (ADS)

Sakharkar, Kishore R.; Sakharkar, Meena K.

The rapid advances and scale up of projects in DNA sequencing dur ing the past two decades have produced complete genome sequences of several eukaryotic species. The versatile genetic malleability of the yeast, and the high degree of conservation between its cellular processes and those of human cells have made it a model of choice for pioneering research in molecular and cell biology. The complete sequence of yeast genome has proven to be extremely useful as a reference towards the sequences of human and for providing systems to explore key gene functions. Yeast has been a ‘legendary model’ for new technologies and gaining new biological insights into basic biological sciences and biotechnology. This chapter describes the awesome power of yeast genetics, genomics and proteomics in understanding of biological function. The applications of yeast as a screening tool to the field of drug discovery and development are highlighted and the traditional importance of yeast for bakers and brewers is discussed.

The Reconstruction and Analysis of Gene Regulatory Networks.

PubMed

Zheng, Guangyong; Huang, Tao

2018-01-01

In post-genomic era, an important task is to explore the function of individual biological molecules (i.e., gene, noncoding RNA, protein, metabolite) and their organization in living cells. For this end, gene regulatory networks (GRNs) are constructed to show relationship between biological molecules, in which the vertices of network denote biological molecules and the edges of network present connection between nodes (Strogatz, Nature 410:268-276, 2001; Bray, Science 301:1864-1865, 2003). Biologists can understand not only the function of biological molecules but also the organization of components of living cells through interpreting the GRNs, since a gene regulatory network is a comprehensively physiological map of living cells and reflects influence of genetic and epigenetic factors (Strogatz, Nature 410:268-276, 2001; Bray, Science 301:1864-1865, 2003). In this paper, we will review the inference methods of GRN reconstruction and analysis approaches of network structure. As a powerful tool for studying complex diseases and biological processes, the applications of the network method in pathway analysis and disease gene identification will be introduced.

Darwin's legacy: the forms, function and sexual diversity of flowers

PubMed Central

Barrett, Spencer C. H.

2010-01-01

Charles Darwin studied floral biology for over 40 years and wrote three major books on plant reproduction. These works have provided the conceptual foundation for understanding floral adaptations that promote cross-fertilization and the mechanisms responsible for evolutionary transitions in reproductive systems. Many of Darwin's insights, gained from careful observations and experiments on diverse angiosperm species, remain remarkably durable today and have stimulated much current research on floral function and the evolution of mating systems. Here I review Darwin's seminal contributions to reproductive biology and provide an overview of the current status of research on several of the main topics to which he devoted considerable effort, including the consequences to fitness of cross- versus self-fertilization, the evolution and function of stylar polymorphisms, the adaptive significance of heteranthery, the origins of dioecy and related gender polymorphisms, and the transition from animal pollination to wind pollination. Post-Darwinian perspectives on floral function now recognize the importance of pollen dispersal and male outcrossed siring success in shaping floral adaptation. This has helped to link work on pollination biology and mating systems, two subfields of reproductive biology that remained largely isolated during much of the twentieth century despite Darwin's efforts towards integration. PMID:20047864

Air pollution particles and iron homeostasis | Science ...

EPA Pesticide Factsheets

Background: The mechanism underlying biological effects of particles deposited in the lung has not been defined. Major Conclusions: A disruption in iron homeostasis follows exposure of cells to all particulate matter including air pollution particles. Following endocytosis, functional groups at the surface of retained particle complex iron available in the cell. In response to a reduction in concentrations of requisite iron, a functional deficiency can result intracellularly. Superoxide production by the cell exposed to a particle increases ferrireduction which facilitates import of iron with the objective being the reversal of the metal deficiency. Failure to resolve the functional iron deficiency following cell exposure to particles activates kinases and transcription factors resulting in a release of inflammatory mediators and inflammation. Tissue injury is the end product of this disruption in iron homeostasis initiated by the particle exposure. Elevation of available iron to the cell precludes deficiency of the metal and either diminishes or eliminates biological effects.General Significance: Recognition of the pathway for biological effects after particle exposure to involve a functional deficiency of iron suggests novel therapies such as metal supplementation (e.g. inhaled and oral). In addition, the demonstration of a shared mechanism of biological effects allows understanding the common clinical, physiological, and pathological presentation fol

Biology of teeth and implants: Host factors - pathology, regeneration, and the role of stem cells.

PubMed

Eggert, F-Michael; Levin, Liran

2018-01-01

In chronic periodontitis and peri-implantitis, cells of the innate and adaptive immune systems are involved directly in the lesions within the tissues of the patient. Absence of a periodontal ligament around implants does not prevent a biologic process similar to that of periodontitis from affecting osseointegration. Our first focus is on factors in the biology of individuals that are responsible for the susceptibility of such individuals to chronic periodontitis and to peri-implantitis. Genetic factors are of significant importance in susceptibility to these diseases. Genetic factors of the host affect the composition of the oral microbiome in the same manner that they influence other microbiomes, such as those of the intestines and of the lungs. Our second focus is on the central role of stem cells in tissue regeneration, in the functioning of innate and adaptive immune systems, and in metabolism of bone. Epithelial cell rests of Malassez (ERM) are stem cells of epithelial origin that maintain the periodontal ligament as well as the cementum and alveolar bone associated with the ligament. The tissue niche within which ERM are found extends into the supracrestal areas of collagen fiber-containing tissues of the gingivae above the bony alveolar crest. Maintenance and regeneration of all periodontal tissues involves the activity of a variety of stem cells. The success of dental implants indicates that important groups of stem cells in the periodontium are active to enable that biologic success. Successful replantation of avulsed teeth and auto-transplantation of teeth is comparable to placing dental implants, and so must also involve periodontal stem cells. Biology of teeth and biology of implants represents the biology of the various stem cells that inhabit specialized niches within the periodontal tissues. Diverse biologic processes must function together successfully to maintain periodontal health. Osseointegration of dental implants does not involve formation of cementum or collagen fibers inserted into cementum - indicating that some stem cells are not active around dental implants or their niches are not available. Investigation of these similarities and differences between teeth and implants will help to develop a better understanding of the biology and physiologic functioning of the periodontium.

Mining for Micropeptides.

PubMed

Makarewich, Catherine A; Olson, Eric N

2017-09-01

Advances in computational biology and large-scale transcriptome analyses have revealed that a much larger portion of the genome is transcribed than was previously recognized, resulting in the production of a diverse population of RNA molecules with both protein-coding and noncoding potential. Emerging evidence indicates that several RNA molecules have been mis-annotated as noncoding and in fact harbor short open reading frames (sORFs) that encode functional peptides and that have evaded detection until now due to their small size. sORF-encoded peptides (SEPs), or micropeptides, have been shown to have important roles in fundamental biological processes and in the maintenance of cellular homeostasis. These small proteins can act independently, for example as ligands or signaling molecules, or they can exert their biological functions by engaging with and modulating larger regulatory proteins. Given their small size, micropeptides may be uniquely suited to fine-tune complex biological systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Foreword to 'Multiscale structural biology: biophysical principles and mechanisms underlying the action of bio-nanomachines', a special issue in Honour of Fumio Arisaka's 70th birthday.

PubMed

Hall, Damien; Takagi, Junichi; Nakamura, Haruki

2018-04-01

This issue of Biophysical Reviews, titled 'Multiscale structural biology: biophysical principles and mechanisms underlying the action of bio-nanomachines', is a collection of articles dedicated in honour of Professor Fumio Arisaka's 70th birthday. Initially, working in the fields of haemocyanin and actin filament assembly, Fumio went on to publish important work on the elucidation of structural and functional aspects of T4 phage biology. As his career has transitioned levels of complexity from proteins (hemocyanin) to large protein complexes (actin) to even more massive bio-nanomachinery (phage), it is fitting that the subject of this special issue is similarly reflective of his multiscale approach to structural biology. This festschrift contains articles spanning biophysical structure and function from the bio-molecular through to the bio-nanomachine level.

Design of synthetic biological logic circuits based on evolutionary algorithm.

PubMed

Chuang, Chia-Hua; Lin, Chun-Liang; Chang, Yen-Chang; Jennawasin, Tanagorn; Chen, Po-Kuei

2013-08-01

The construction of an artificial biological logic circuit using systematic strategy is recognised as one of the most important topics for the development of synthetic biology. In this study, a real-structured genetic algorithm (RSGA), which combines general advantages of the traditional real genetic algorithm with those of the structured genetic algorithm, is proposed to deal with the biological logic circuit design problem. A general model with the cis-regulatory input function and appropriate promoter activity functions is proposed to synthesise a wide variety of fundamental logic gates such as NOT, Buffer, AND, OR, NAND, NOR and XOR. The results obtained can be extended to synthesise advanced combinational and sequential logic circuits by topologically distinct connections. The resulting optimal design of these logic gates and circuits are established via the RSGA. The in silico computer-based modelling technology has been verified showing its great advantages in the purpose.

Darwinism and the cultural evolution of sports.

PubMed

De Block, Andreas; Dewitte, Siegfried

2009-01-01

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

Long non-coding RNAs and their biological roles in plants.

PubMed

Liu, Xue; Hao, Lili; Li, Dayong; Zhu, Lihuang; Hu, Songnian

2015-06-01

With the development of genomics and bioinformatics, especially the extensive applications of high-throughput sequencing technology, more transcriptional units with little or no protein-coding potential have been discovered. Such RNA molecules are called non-protein-coding RNAs (npcRNAs or ncRNAs). Among them, long npcRNAs or ncRNAs (lnpcRNAs or lncRNAs) represent diverse classes of transcripts longer than 200 nucleotides. In recent years, the lncRNAs have been considered as important regulators in many essential biological processes. In plants, although a large number of lncRNA transcripts have been predicted and identified in few species, our current knowledge of their biological functions is still limited. Here, we have summarized recent studies on their identification, characteristics, classification, bioinformatics, resources, and current exploration of their biological functions in plants. Copyright © 2015 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

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

PubMed

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

2018-04-01

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

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

PubMed

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

2018-05-01

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

The Role of Noise in Brain Function

NASA Astrophysics Data System (ADS)

Roy, S.; Llinás, R.

2012-12-01

Noise plays a fundamental role in all living organisms from the earliest prokaryotes to advanced mammalian forms, such as ourselves. In the context of living organisms, the term 'noise' usually refers to the variance amongst measurements obtained from repeated identical experimental conditions, or from output signals from these systems. It is noteworthy that both these conditions are universally characterized by the presence of background fluctuations. In non-biological systems, such as electronics or in communications sciences, where the aim is to send error-free messages, noise was generally regarded as a problem. The discovery of Stochastic Resonances (SR) in non-linear dynamics brought a shift of perception where noise, rather than representing a problem, became fundamental to system function, especially so in biology. The question now is: to what extent is biological function dependent on random noise. Indeed, it seems feasible that noise also plays an important role in neuronal communication and oscillatory synchronization. Given this approach, it follows that determining Fisher information content could be relevant in neuronal communication. It also seems possible that the principle of least time, and that of the sum over histories, could be important basic principles in understanding the coherence dynamics responsible for action and perception. Ultimately, external noise cancellation combined with intrinsic noise signal embedding and, the use of the principle of least time may be considered an essential step in the organization of central nervous system (CNS) function.

On the debate about teleology in biology: the notion of "teleological obstacle".

PubMed

Ribeiro, Manuel Gustavo Leitão; Larentis, Ariane Leites; Caldas, Lúcio Ayres; Garcia, Tomás Coelho; Terra, Letícia Labati; Herbst, Marcelo Hawrylak; Almeida, Rodrigo Volcan

2015-12-01

Among the epistemological obstacles described by Gaston Bachelard, we contend that unitary and pragmatic knowledge is correlated to the teleological categories of Ernst Mayr and is the basis for prevailing debate on the notion of "function" in biology. Given the proximity of the aspects highlighted by these authors, we propose to associate the role of teleological thinking in biology and the notion of unitary and pragmatic knowledge as an obstacle to scientific knowledge. Thus, teleological thinking persists acting as an epistemological obstacle in biology, according to Bachelardian terminology. Our investigation led us to formulate the "teleological obstacle," which we consider important for the future of biology and possibly other sciences.

[Long non-coding RNAs in plants].

PubMed

Xiaoqing, Huang; Dandan, Li; Juan, Wu

2015-04-01

Long non-coding RNAs (lncRNAs), which are longer than 200 nucleotides in length, widely exist in organisms and function in a variety of biological processes. Currently, most of lncRNAs found in plants are transcribed by RNA polymerase Ⅱ and mediate gene expression through multiple mechanisms, such as target mimicry, transcription interference, histone methylation and DNA methylation, and play important roles in flowering, male sterility, nutrition metabolism, biotic and abiotic stress and other biological processes as regulators in plants. In this review, we summarize the databases, prediction methods, and possible functions of plant lncRNAs discovered in recent years.

Impaired visual recognition of biological motion in schizophrenia.

PubMed

Kim, Jejoong; Doop, Mikisha L; Blake, Randolph; Park, Sohee

2005-09-15

Motion perception deficits have been suggested to be an important feature of schizophrenia but the behavioral consequences of such deficits are unknown. Biological motion refers to the movements generated by living beings. The human visual system rapidly and effortlessly detects and extracts socially relevant information from biological motion. A deficit in biological motion perception may have significant consequences for detecting and interpreting social information. Schizophrenia patients and matched healthy controls were tested on two visual tasks: recognition of human activity portrayed in point-light animations (biological motion task) and a perceptual control task involving detection of a grouped figure against the background noise (global-form task). Both tasks required detection of a global form against background noise but only the biological motion task required the extraction of motion-related information. Schizophrenia patients performed as well as the controls in the global-form task, but were significantly impaired on the biological motion task. In addition, deficits in biological motion perception correlated with impaired social functioning as measured by the Zigler social competence scale [Zigler, E., Levine, J. (1981). Premorbid competence in schizophrenia: what is being measured? Journal of Consulting and Clinical Psychology, 49, 96-105.]. The deficit in biological motion processing, which may be related to the previously documented deficit in global motion processing, could contribute to abnormal social functioning in schizophrenia.

Organic core-sheath nanowire artificial synapses with femtojoule energy consumption.

PubMed

Xu, Wentao; Min, Sung-Yong; Hwang, Hyunsang; Lee, Tae-Woo

2016-06-01

Emulation of biological synapses is an important step toward construction of large-scale brain-inspired electronics. Despite remarkable progress in emulating synaptic functions, current synaptic devices still consume energy that is orders of magnitude greater than do biological synapses (~10 fJ per synaptic event). Reduction of energy consumption of artificial synapses remains a difficult challenge. We report organic nanowire (ONW) synaptic transistors (STs) that emulate the important working principles of a biological synapse. The ONWs emulate the morphology of nerve fibers. With a core-sheath-structured ONW active channel and a well-confined 300-nm channel length obtained using ONW lithography, ~1.23 fJ per synaptic event for individual ONW was attained, which rivals that of biological synapses. The ONW STs provide a significant step toward realizing low-energy-consuming artificial intelligent electronics and open new approaches to assembling soft neuromorphic systems with nanometer feature size.

Cre/lox-recombinase-mediated cassette exchange for reversible site-specific genomic targeting of the disease vector, Aedes aegypti

USDA-ARS?s Scientific Manuscript database

Site-specific genome modification is an important tool for mosquito functional genomics studies that help to uncover gene functions, identify gene regulatory elements, and perform comparative gene expression studies, all of which contribute to a better understanding of mosquito biology and are thus ...

Lineage-specific genomics: Frequent birth and death in the human genome: The human genome contains many lineage-specific elements created by both sequence and functional turnover.

PubMed

Young, Robert S

2016-07-01

Frequent evolutionary birth and death events have created a large quantity of biologically important, lineage-specific DNA within mammalian genomes. The birth and death of DNA sequences is so frequent that the total number of these insertions and deletions in the human population remains unknown, although there are differences between these groups, e.g. transposable elements contribute predominantly to sequence insertion. Functional turnover - where the activity of a locus is specific to one lineage, but the underlying DNA remains conserved - can also drive birth and death. However, this does not appear to be a major driver of divergent transcriptional regulation. Both sequence and functional turnover have contributed to the birth and death of thousands of functional promoters in the human and mouse genomes. These findings reveal the pervasive nature of evolutionary birth and death and suggest that lineage-specific regions may play an important but previously underappreciated role in human biology and disease. © 2016 The Authors BioEssays Published by WILEY Periodicals, Inc.

Multi-walled carbon nanotubes and metallic nanoparticles and their application in biomedicine.

PubMed

Rojas-Chapana, Jose A; Giersig, Michael

2006-02-01

Interdisciplinary research has become a matter of paramount importance for novel applications of nanomaterials in biology and medicine. As such, many disciplines-physics, chemistry, microbiology, cell biology, and material science-all contribute to the design, synthesis and fabrication of functional and biocompatible devices at the nanometer scale. Since the most areas of cell biology and biomedicine deal with functional entities such as DNA and proteins, mimicry of these structures and function in the nanosize range offers exciting opportunities for the development of biosensors, biochips, and bioplatforms. In this report we highlight the potential benefits and challenges that arise in the manufacture of biocompatible nanoparticles and nano-networks that can be coupled with biological objects. Among the challenges facing us are those concerned with making the necessary advances in enabling affordability, innovation, and quality of manufactured nanodevices for rapid progress in the emerging field of bio-nanotechnology. The convergence of nanotechnology and biomedicine makes nanoscale research highly promising for new discoveries that can cost-effectively accelerate progress in moving from basic research to practical prototypes and products.

Atom-scale depth localization of biologically important chemical elements in molecular layers.

PubMed

Schneck, Emanuel; Scoppola, Ernesto; Drnec, Jakub; Mocuta, Cristian; Felici, Roberto; Novikov, Dmitri; Fragneto, Giovanna; Daillant, Jean

2016-08-23

In nature, biomolecules are often organized as functional thin layers in interfacial architectures, the most prominent examples being biological membranes. Biomolecular layers play also important roles in context with biotechnological surfaces, for instance, when they are the result of adsorption processes. For the understanding of many biological or biotechnologically relevant phenomena, detailed structural insight into the involved biomolecular layers is required. Here, we use standing-wave X-ray fluorescence (SWXF) to localize chemical elements in solid-supported lipid and protein layers with near-Ångstrom precision. The technique complements traditional specular reflectometry experiments that merely yield the layers' global density profiles. While earlier work mostly focused on relatively heavy elements, typically metal ions, we show that it is also possible to determine the position of the comparatively light elements S and P, which are found in the most abundant classes of biomolecules and are therefore particularly important. With that, we overcome the need of artificial heavy atom labels, the main obstacle to a broader application of high-resolution SWXF in the fields of biology and soft matter. This work may thus constitute the basis for the label-free, element-specific structural investigation of complex biomolecular layers and biological surfaces.

Atom-scale depth localization of biologically important chemical elements in molecular layers

PubMed Central

Schneck, Emanuel; Scoppola, Ernesto; Drnec, Jakub; Mocuta, Cristian; Felici, Roberto; Novikov, Dmitri; Fragneto, Giovanna; Daillant, Jean

2016-01-01

In nature, biomolecules are often organized as functional thin layers in interfacial architectures, the most prominent examples being biological membranes. Biomolecular layers play also important roles in context with biotechnological surfaces, for instance, when they are the result of adsorption processes. For the understanding of many biological or biotechnologically relevant phenomena, detailed structural insight into the involved biomolecular layers is required. Here, we use standing-wave X-ray fluorescence (SWXF) to localize chemical elements in solid-supported lipid and protein layers with near-Ångstrom precision. The technique complements traditional specular reflectometry experiments that merely yield the layers’ global density profiles. While earlier work mostly focused on relatively heavy elements, typically metal ions, we show that it is also possible to determine the position of the comparatively light elements S and P, which are found in the most abundant classes of biomolecules and are therefore particularly important. With that, we overcome the need of artificial heavy atom labels, the main obstacle to a broader application of high-resolution SWXF in the fields of biology and soft matter. This work may thus constitute the basis for the label-free, element-specific structural investigation of complex biomolecular layers and biological surfaces. PMID:27503887

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

PubMed Central

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

2010-01-01

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

Systems biology definition of the core proteome of metabolism and expression is consistent with high-throughput data.

PubMed

Yang, Laurence; Tan, Justin; O'Brien, Edward J; Monk, Jonathan M; Kim, Donghyuk; Li, Howard J; Charusanti, Pep; Ebrahim, Ali; Lloyd, Colton J; Yurkovich, James T; Du, Bin; Dräger, Andreas; Thomas, Alex; Sun, Yuekai; Saunders, Michael A; Palsson, Bernhard O

2015-08-25

Finding the minimal set of gene functions needed to sustain life is of both fundamental and practical importance. Minimal gene lists have been proposed by using comparative genomics-based core proteome definitions. A definition of a core proteome that is supported by empirical data, is understood at the systems-level, and provides a basis for computing essential cell functions is lacking. Here, we use a systems biology-based genome-scale model of metabolism and expression to define a functional core proteome consisting of 356 gene products, accounting for 44% of the Escherichia coli proteome by mass based on proteomics data. This systems biology core proteome includes 212 genes not found in previous comparative genomics-based core proteome definitions, accounts for 65% of known essential genes in E. coli, and has 78% gene function overlap with minimal genomes (Buchnera aphidicola and Mycoplasma genitalium). Based on transcriptomics data across environmental and genetic backgrounds, the systems biology core proteome is significantly enriched in nondifferentially expressed genes and depleted in differentially expressed genes. Compared with the noncore, core gene expression levels are also similar across genetic backgrounds (two times higher Spearman rank correlation) and exhibit significantly more complex transcriptional and posttranscriptional regulatory features (40% more transcription start sites per gene, 22% longer 5'UTR). Thus, genome-scale systems biology approaches rigorously identify a functional core proteome needed to support growth. This framework, validated by using high-throughput datasets, facilitates a mechanistic understanding of systems-level core proteome function through in silico models; it de facto defines a paleome.

LincRNA-p21: Implications in Human Diseases.

PubMed

Tang, Sai-Sai; Zheng, Bi-Ying; Xiong, Xing-Dong

2015-08-11

Long noncoding RNAs (lncRNAs), which lack significant protein-coding capacity, regulate various biological processes through diverse and as yet poorly understood molecular mechanisms. However, a number of studies in the past few years have documented important functions for lncRNAs in human diseases. Among these lncRNAs, lincRNA-p21 has been proposed to be a novel regulator of cell proliferation, apoptosis and DNA damage response, and involved in the initiation and progression of human diseases. In this review, we summarize the current knowledge of lincRNA-p21, mainly focus on the known biological functions and its underlying mechanisms. Moreover, we highlight the growing body of evidences for the importance of lincRNA-p21 in diverse human diseases, which indicate lincRNA-p21 as a potential diagnostic marker and/or a valuable therapeutic target for these diseases.

Inverse statistical physics of protein sequences: a key issues review.

PubMed

Cocco, Simona; Feinauer, Christoph; Figliuzzi, Matteo; Monasson, Rémi; Weigt, Martin

2018-03-01

In the course of evolution, proteins undergo important changes in their amino acid sequences, while their three-dimensional folded structure and their biological function remain remarkably conserved. Thanks to modern sequencing techniques, sequence data accumulate at unprecedented pace. This provides large sets of so-called homologous, i.e. evolutionarily related protein sequences, to which methods of inverse statistical physics can be applied. Using sequence data as the basis for the inference of Boltzmann distributions from samples of microscopic configurations or observables, it is possible to extract information about evolutionary constraints and thus protein function and structure. Here we give an overview over some biologically important questions, and how statistical-mechanics inspired modeling approaches can help to answer them. Finally, we discuss some open questions, which we expect to be addressed over the next years.

Inverse statistical physics of protein sequences: a key issues review

NASA Astrophysics Data System (ADS)

Cocco, Simona; Feinauer, Christoph; Figliuzzi, Matteo; Monasson, Rémi; Weigt, Martin

2018-03-01

In the course of evolution, proteins undergo important changes in their amino acid sequences, while their three-dimensional folded structure and their biological function remain remarkably conserved. Thanks to modern sequencing techniques, sequence data accumulate at unprecedented pace. This provides large sets of so-called homologous, i.e. evolutionarily related protein sequences, to which methods of inverse statistical physics can be applied. Using sequence data as the basis for the inference of Boltzmann distributions from samples of microscopic configurations or observables, it is possible to extract information about evolutionary constraints and thus protein function and structure. Here we give an overview over some biologically important questions, and how statistical-mechanics inspired modeling approaches can help to answer them. Finally, we discuss some open questions, which we expect to be addressed over the next years.

The Rules and Functions of Nucleocytoplasmic Shuttling Proteins.

PubMed

Fu, Xuekun; Liang, Chao; Li, Fangfei; Wang, Luyao; Wu, Xiaoqiu; Lu, Aiping; Xiao, Guozhi; Zhang, Ge

2018-05-12

Biological macromolecules are the basis of life activities. There is a separation of spatial dimension between DNA replication and RNA biogenesis, and protein synthesis, which is an interesting phenomenon. The former occurs in the cell nucleus, while the latter in the cytoplasm. The separation requires protein to transport across the nuclear envelope to realize a variety of biological functions. Nucleocytoplasmic transport of protein including import to the nucleus and export to the cytoplasm is a complicated process that requires involvement and interaction of many proteins. In recent years, many studies have found that proteins constantly shuttle between the cytoplasm and the nucleus. These shuttling proteins play a crucial role as transport carriers and signal transduction regulators within cells. In this review, we describe the mechanism of nucleocytoplasmic transport of shuttling proteins and summarize some important diseases related shuttling proteins.

Metabolomics: Definitions and Significance in Systems Biology.

PubMed

Klassen, Aline; Faccio, Andréa Tedesco; Canuto, Gisele André Baptista; da Cruz, Pedro Luis Rocha; Ribeiro, Henrique Caracho; Tavares, Marina Franco Maggi; Sussulini, Alessandra

2017-01-01

Nowadays, there is a growing interest in deeply understanding biological mechanisms not only at the molecular level (biological components) but also the effects of an ongoing biological process in the organism as a whole (biological functionality), as established by the concept of systems biology. Within this context, metabolomics is one of the most powerful bioanalytical strategies that allow obtaining a picture of the metabolites of an organism in the course of a biological process, being considered as a phenotyping tool. Briefly, metabolomics approach consists in identifying and determining the set of metabolites (or specific metabolites) in biological samples (tissues, cells, fluids, or organisms) under normal conditions in comparison with altered states promoted by disease, drug treatment, dietary intervention, or environmental modulation. The aim of this chapter is to review the fundamentals and definitions used in the metabolomics field, as well as to emphasize its importance in systems biology and clinical studies.

Genome projects and the functional-genomic era.

PubMed

Sauer, Sascha; Konthur, Zoltán; Lehrach, Hans

2005-12-01

The problems we face today in public health as a result of the -- fortunately -- increasing age of people and the requirements of developing countries create an urgent need for new and innovative approaches in medicine and in agronomics. Genomic and functional genomic approaches have a great potential to at least partially solve these problems in the future. Important progress has been made by procedures to decode genomic information of humans, but also of other key organisms. The basic comprehension of genomic information (and its transfer) should now give us the possibility to pursue the next important step in life science eventually leading to a basic understanding of biological information flow; the elucidation of the function of all genes and correlative products encoded in the genome, as well as the discovery of their interactions in a molecular context and the response to environmental factors. As a result of the sequencing projects, we are now able to ask important questions about sequence variation and can start to comprehensively study the function of expressed genes on different levels such as RNA, protein or the cell in a systematic context including underlying networks. In this article we review and comment on current trends in large-scale systematic biological research. A particular emphasis is put on technology developments that can provide means to accomplish the tasks of future lines of functional genomics.

DNA is structured as a linear "jigsaw puzzle" in the genomes of Arabidopsis, rice, and budding yeast.

PubMed

Liu, Yun-Hua; Zhang, Meiping; Wu, Chengcang; Huang, James J; Zhang, Hong-Bin

2014-01-01

Knowledge of how a genome is structured and organized from its constituent elements is crucial to understanding its biology and evolution. Here, we report the genome structuring and organization pattern as revealed by systems analysis of the sequences of three model species, Arabidopsis, rice and yeast, at the whole-genome and chromosome levels. We found that all fundamental function elements (FFE) constituting the genomes, including genes (GEN), DNA transposable elements (DTE), retrotransposable elements (RTE), simple sequence repeats (SSR), and (or) low complexity repeats (LCR), are structured in a nonrandom and correlative manner, thus leading to a hypothesis that the DNA of the species is structured as a linear "jigsaw puzzle". Furthermore, we showed that different FFE differ in their importance in the formation and evolution of the DNA jigsaw puzzle structure between species. DTE and RTE play more important roles than GEN, LCR, and SSR in Arabidopsis, whereas GEN and RTE play more important roles than LCR, SSR, and DTE in rice. The genes having multiple recognized functions play more important roles than those having single functions. These results provide useful knowledge necessary for better understanding genome biology and evolution of the species and for effective molecular breeding of rice.

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

PubMed Central

Loewith, Robbie; Hall, Michael N.

2011-01-01

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

L-GRAAL: Lagrangian graphlet-based network aligner.

PubMed

Malod-Dognin, Noël; Pržulj, Nataša

2015-07-01

Discovering and understanding patterns in networks of protein-protein interactions (PPIs) is a central problem in systems biology. Alignments between these networks aid functional understanding as they uncover important information, such as evolutionary conserved pathways, protein complexes and functional orthologs. A few methods have been proposed for global PPI network alignments, but because of NP-completeness of underlying sub-graph isomorphism problem, producing topologically and biologically accurate alignments remains a challenge. We introduce a novel global network alignment tool, Lagrangian GRAphlet-based ALigner (L-GRAAL), which directly optimizes both the protein and the interaction functional conservations, using a novel alignment search heuristic based on integer programming and Lagrangian relaxation. We compare L-GRAAL with the state-of-the-art network aligners on the largest available PPI networks from BioGRID and observe that L-GRAAL uncovers the largest common sub-graphs between the networks, as measured by edge-correctness and symmetric sub-structures scores, which allow transferring more functional information across networks. We assess the biological quality of the protein mappings using the semantic similarity of their Gene Ontology annotations and observe that L-GRAAL best uncovers functionally conserved proteins. Furthermore, we introduce for the first time a measure of the semantic similarity of the mapped interactions and show that L-GRAAL also uncovers best functionally conserved interactions. In addition, we illustrate on the PPI networks of baker's yeast and human the ability of L-GRAAL to predict new PPIs. Finally, L-GRAAL's results are the first to show that topological information is more important than sequence information for uncovering functionally conserved interactions. L-GRAAL is coded in C++. Software is available at: http://bio-nets.doc.ic.ac.uk/L-GRAAL/. n.malod-dognin@imperial.ac.uk Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

Recent advances in biomimetic sensing technologies.

PubMed

Johnson, E A C; Bonser, R H C; Jeronimidis, G

2009-04-28

The importance of biological materials has long been recognized from the molecular level to higher levels of organization. Whereas, in traditional engineering, hardness and stiffness are considered desirable properties in a material, biology makes considerable and advantageous use of softer, more pliable resources. The development, structure and mechanics of these materials are well documented and will not be covered here. The purpose of this paper is, however, to demonstrate the importance of such materials and, in particular, the functional structures they form. Using only a few simple building blocks, nature is able to develop a plethora of diverse materials, each with a very different set of mechanical properties and from which a seemingly impossibly large number of assorted structures are formed. There is little doubt that this is made possible by the fact that the majority of biological 'materials' or 'structures' are based on fibres and that these fibres provide opportunities for functional hierarchies. We show how these structures have inspired a new generation of innovative technologies in the science and engineering community. Particular attention is given to the use of insects as models for biomimetically inspired innovations.

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

PubMed Central

Dewhurst, Henry; Sundararaman, Niveda

2016-01-01

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

Biological and functional relevance of CASP predictions

PubMed Central

Liu, Tianyun; Ish‐Shalom, Shirbi; Torng, Wen; Lafita, Aleix; Bock, Christian; Mort, Matthew; Cooper, David N; Bliven, Spencer; Capitani, Guido; Mooney, Sean D.

2017-01-01

Abstract Our goal is to answer the question: compared with experimental structures, how useful are predicted models for functional annotation? We assessed the functional utility of predicted models by comparing the performances of a suite of methods for functional characterization on the predictions and the experimental structures. We identified 28 sites in 25 protein targets to perform functional assessment. These 28 sites included nine sites with known ligand binding (holo‐sites), nine sites that are expected or suggested by experimental authors for small molecule binding (apo‐sites), and Ten sites containing important motifs, loops, or key residues with important disease‐associated mutations. We evaluated the utility of the predictions by comparing their microenvironments to the experimental structures. Overall structural quality correlates with functional utility. However, the best‐ranked predictions (global) may not have the best functional quality (local). Our assessment provides an ability to discriminate between predictions with high structural quality. When assessing ligand‐binding sites, most prediction methods have higher performance on apo‐sites than holo‐sites. Some servers show consistently high performance for certain types of functional sites. Finally, many functional sites are associated with protein‐protein interaction. We also analyzed biologically relevant features from the protein assemblies of two targets where the active site spanned the protein‐protein interface. For the assembly targets, we find that the features in the models are mainly determined by the choice of template. PMID:28975675

Cerebellar-inspired algorithm for adaptive control of nonlinear dielectric elastomer-based artificial muscle

PubMed Central

Assaf, Tareq; Rossiter, Jonathan M.; Porrill, John

2016-01-01

Electroactive polymer actuators are important for soft robotics, but can be difficult to control because of compliance, creep and nonlinearities. Because biological control mechanisms have evolved to deal with such problems, we investigated whether a control scheme based on the cerebellum would be useful for controlling a nonlinear dielectric elastomer actuator, a class of artificial muscle. The cerebellum was represented by the adaptive filter model, and acted in parallel with a brainstem, an approximate inverse plant model. The recurrent connections between the two allowed for direct use of sensory error to adjust motor commands. Accurate tracking of a displacement command in the actuator's nonlinear range was achieved by either semi-linear basis functions in the cerebellar model or semi-linear functions in the brainstem corresponding to recruitment in biological muscle. In addition, allowing transfer of training between cerebellum and brainstem as has been observed in the vestibulo-ocular reflex prevented the steady increase in cerebellar output otherwise required to deal with creep. The extensibility and relative simplicity of the cerebellar-based adaptive-inverse control scheme suggests that it is a plausible candidate for controlling this type of actuator. Moreover, its performance highlights important features of biological control, particularly nonlinear basis functions, recruitment and transfer of training. PMID:27655667

The city as a refuge for insect pollinators.

PubMed

Hall, Damon M; Camilo, Gerardo R; Tonietto, Rebecca K; Ollerton, Jeff; Ahrné, Karin; Arduser, Mike; Ascher, John S; Baldock, Katherine C R; Fowler, Robert; Frankie, Gordon; Goulson, Dave; Gunnarsson, Bengt; Hanley, Mick E; Jackson, Janet I; Langellotto, Gail; Lowenstein, David; Minor, Emily S; Philpott, Stacy M; Potts, Simon G; Sirohi, Muzafar H; Spevak, Edward M; Stone, Graham N; Threlfall, Caragh G

2017-02-01

Research on urban insect pollinators is changing views on the biological value and ecological importance of cities. The abundance and diversity of native bee species in urban landscapes that are absent in nearby rural lands evidence the biological value and ecological importance of cities and have implications for biodiversity conservation. Lagging behind this revised image of the city are urban conservation programs that historically have invested in education and outreach rather than programs designed to achieve high-priority species conservation results. We synthesized research on urban bee species diversity and abundance to determine how urban conservation could be repositioned to better align with new views on the ecological importance of urban landscapes. Due to insect pollinators' relatively small functional requirements-habitat range, life cycle, and nesting behavior-relative to larger mammals, we argue that pollinators put high-priority and high-impact urban conservation within reach. In a rapidly urbanizing world, transforming how environmental managers view the city can improve citizen engagement and contribute to the development of more sustainable urbanization. © 2016 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

Meniscal Preservation is Important for the Knee Joint

PubMed Central

Patil, Shantanu Sudhakar; Shekhar, Anshu; Tapasvi, Sachin Ramchandra

2017-01-01

Native joint preservation has gained importance in recent years. This is mostly to find solutions for limitations of arthroplasty. In the knee joint, the menisci perform critical functions, adding stability during range of motion and efficiently transferring load across the tibiofemoral articulation while protecting the cartilage. The menisci are the most common injury seen by orthopedicians, especially in the younger active patients. Advances in technology and our knowledge on functioning of the knee joint have made meniscus repair an important mode of treatment. This review summarizes the various techniques of meniscus tear repair and also describes biological enhancements of healing. PMID:28966381

Future directions of electron crystallography.

PubMed

Fujiyoshi, Yoshinori

2013-01-01

In biological science, there are still many interesting and fundamental yet difficult questions, such as those in neuroscience, remaining to be answered. Structural and functional studies of membrane proteins, which are key molecules of signal transduction in neural and other cells, are essential for understanding the molecular mechanisms of many fundamental biological processes. Technological and instrumental advancements of electron microscopy have facilitated comprehension of structural studies of biological components, such as membrane proteins. While X-ray crystallography has been the main method of structure analysis of proteins including membrane proteins, electron crystallography is now an established technique to analyze structures of membrane proteins in the lipid bilayer, which is close to their natural biological environment. By utilizing cryo-electron microscopes with helium-cooled specimen stages, structures of membrane proteins were analyzed at a resolution better than 3 Å. Such high-resolution structural analysis of membrane proteins by electron crystallography opens up the new research field of structural physiology. Considering the fact that the structures of integral membrane proteins in their native membrane environment without artifacts from crystal contacts are critical in understanding their physiological functions, electron crystallography will continue to be an important technology for structural analysis. In this chapter, I will present several examples to highlight important advantages and to suggest future directions of this technique.

The 2009 Nobel Prize in Chemistry: Thomas A. Steitz and the structure of the ribosome.

PubMed

Zhao, Peter

2011-06-01

Over the past 200 years, there have been countless groundbreaking discoveries in biology and medicine at Yale University. However, one particularly noteworthy discovery with profoundly important and broad consequences happened here in just the past two decades. In 2009, Thomas Steitz, the Sterling Professor of Molecular Biophysics & Biochemistry, was awarded the Nobel Prize in Chemistry for "studies of the structure and function of the ribosome," along with Venkatraman Ramakrishnan of the MRC Laboratory of Molecular Biology and Ada E. Yonath of the Weizmann Institute of Science. This article covers the historical context of Steitz's important discovery, the techniques his laboratory used to study the ribosome, and the impact that this research has had, and will have, on the future of biological and medical research.

The importance of trace element speciation in biomedical science.

PubMed

Templeton, Douglas M

2003-04-01

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

Microarray gene-expression study in fibroblast and lymphoblastoid cell lines from antipsychotic-naïve first-episode schizophrenia patients.

PubMed

Gassó, Patricia; Mas, Sergi; Rodríguez, Natalia; Boloc, Daniel; García-Cerro, Susana; Bernardo, Miquel; Lafuente, Amalia; Parellada, Eduard

2017-12-01

Schizophrenia (SZ) is a chronic psychiatric disorder whose onset of symptoms occurs in late adolescence and early adulthood. The etiology is complex and involves important gene-environment interactions. Microarray gene-expression studies on SZ have identified alterations in several biological processes. The heterogeneity in the results can be attributed to the use of different sample types and other important confounding factors including age, illness chronicity and antipsychotic exposure. The aim of the present microarray study was to analyze, for the first time to our knowledge, differences in gene expression profiles in 18 fibroblast (FCLs) and 14 lymphoblastoid cell lines (LCLs) from antipsychotic-naïve first-episode schizophrenia (FES) patients and healthy controls. We used an analytical approach based on protein-protein interaction network construction and functional annotation analysis to identify the biological processes that are altered in SZ. Significant differences in the expression of 32 genes were found when LCLs were assessed. The network and gene set enrichment approach revealed the involvement of similar biological processes in FCLs and LCLs, including apoptosis and related biological terms such as cell cycle, autophagy, cytoskeleton organization and response to stress and stimulus. Metabolism and other processes, including signal transduction, kinase activity and phosphorylation, were also identified. These results were replicated in two independent cohorts using the same analytical approach. This provides more evidence for altered apoptotic processes in antipsychotic-naïve FES patients and other important biological functions such as cytoskeleton organization and metabolism. The convergent results obtained in both peripheral cell models support their usefulness for transcriptome studies on SZ. Copyright © 2017 Elsevier Ltd. All rights reserved.

Carotenoids

USDA-ARS?s Scientific Manuscript database

This short article indicated that greater understanding of the biological functions of carotenoids mediated via their oxidative metabolites through their effects on these important cellular pathways and molecular targets, as well as their significance to cancer prevention, is needed. In considering ...

Tested Demonstrations: A Simple Demonstration of Reversible Oxygenation.

ERIC Educational Resources Information Center

Kildahl, Nicholas K.

1983-01-01

Materials needed, reaction involved, and potential hazards are provided for a demonstration of reversible oxygenation. Also discusses the importance of the reaction in biological systems, focusing on hemoglobin/myoglobin and their function in mammals. (JM)

Desmosomes in acquired disease

PubMed Central

Stahley, Sara N.; Kowalczyk, Andrew P.

2015-01-01

Desmosomes are cell-cell junctions that mediate adhesion and couple the intermediate filament cytoskeleton to sites of cell-cell contact. This architectural arrangement functions to integrate adhesion and cytoskeletal elements of adjacent cells. The importance of this robust adhesion system is evident in numerous human diseases, both inherited and acquired, that occur when desmosome function is compromised. This review focuses on autoimmune and infectious diseases that impair desmosome function. In addition, we discuss emerging evidence that desmosomal genes are often misregulated in cancer. The emphasis of our discussion is placed on how human diseases inform our understanding of basic desmosome biology, and in turn, how fundamental advances in the cell biology of desmosomes may lead to new treatments for acquired diseases of the desmosome. PMID:25795143

Video Views and Reviews: Neurulation and the Fashioning of the Vertebrate Central Nervous System

ERIC Educational Resources Information Center

Watters, Christopher

2006-01-01

The central nervous system (CNS) is the first adult organ system to appear during vertebrate development, and the process of its emergence is commonly called neurulation. Such biological "urgency" is perhaps not surprising given the structural and functional complexity of the CNS and the importance of neural function to adaptive behavior and…

Functional Anthology of Intrinsic Disorder. III. Ligands, Postranslational Modifications and Diseases Associated with Intrinsically Disordered Proteins

PubMed Central

Xie, Hongbo; Vucetic, Slobodan; Iakoucheva, Lilia M.; Oldfield, Christopher J.; Dunker, A. Keith; Obradovic, Zoran; Uversky, Vladimir N.

2008-01-01

Currently, the understanding of the relationships between function, amino acid sequence and protein structure continues to represent one of the major challenges of the modern protein science. As much as 50% of eukaryotic proteins are likely to contain functionally important long disordered regions. Many proteins are wholly disordered but still possess numerous biologically important functions. However, the number of experimentally confirmed disordered proteins with known biological functions is substantially smaller than their actual number in nature. Therefore, there is a crucial need for novel bioinformatics approaches that allow projection of the current knowledge from a few experimentally verified examples to much larger groups of known and potential proteins. The elaboration of a bioinformatics tool for the analysis of functional diversity of intrinsically disordered proteins and application of this data mining tool to >200,000 proteins from Swiss-Prot database, each annotated with at least one of the 875 functional keywords was described in the first paper of this series (Xie H., Vucetic S., Iakoucheva L.M., Oldfield C.J., Dunker A.K., Obradovic Z., Uversky V.N. (2006) Functional anthology of intrinsic disorder. I. Biological processes and functions of proteins with long disordered regions. J. Proteome Res.). Using this tool, we have found that out of the 711 Swiss-Prot functional keywords associated with at least 20 proteins, 262 were strongly positively correlated with long intrinsically disordered regions, and 302 were strongly negatively correlated. Illustrative examples of functional disorder or order were found for the vast majority of keywords showing strongest positive or negative correlation with intrinsic disorder, respectively. Some 80 Swiss-Prot keywords associated with disorder- and order-driven biological processes and protein functions were described in the first paper (Xie H., Vucetic S., Iakoucheva L.M., Oldfield C.J., Dunker A.K., Obradovic Z., Uversky V.N. (2006) Functional anthology of intrinsic disorder. I. Biological processes and functions of proteins with long disordered regions. J. Proteome Res.). The second paper of the series was devoted to the presentation of 87 Swiss-Prot keywords attributed to the cellular components, domains, technical terms, developmental processes and coding sequence diversities possessing strong positive and negative correlation with long disordered regions (Vucetic S., Xie H., Iakoucheva L.M., Oldfield C.J., Dunker A.K., Obradovic Z., Uversky V.N. (2006) Functional anthology of intrinsic disorder. II. Cellular components, domains, technical terms, developmental processes and coding sequence diversities correlated with long disordered regions. J. Proteome Res.). Protein structure and functionality can be modulated by various posttranslational modifications or/and as a result of binding of specific ligands. Numerous human diseases are associated with protein misfolding/misassembly/ misfunctioning. This work concludes the series of papers dedicated to the functional anthology of intrinsic disorder and describes ~80 Swiss-Prot functional keywords that are related to ligands, posttranslational modifications and diseases possessing strong positive or negative correlation with the predicted long disordered regions in proteins. PMID:17391016

Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence

PubMed Central

Terasaki, Kaori; Ramirez, Sydney I.; Makino, Shinji

2016-01-01

Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear. To examine this, we generated two RVFV MP-12 strain-derived mutant viruses. Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter. Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence. Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12. It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit. Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice, compared with its parental virus MP-12, highlighting the contribution of NSs-mediated general transcription inhibition towards RVFV virulence. PMID:27711108

Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence.

PubMed

Terasaki, Kaori; Ramirez, Sydney I; Makino, Shinji

2016-10-01

Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear. To examine this, we generated two RVFV MP-12 strain-derived mutant viruses. Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter. Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence. Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12. It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit. Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice, compared with its parental virus MP-12, highlighting the contribution of NSs-mediated general transcription inhibition towards RVFV virulence.

Forest genetic monitoring: an overview of concepts and definitions.

PubMed

Fussi, Barbara; Westergren, Marjana; Aravanopoulos, Filippos; Baier, Roland; Kavaliauskas, Darius; Finzgar, Domen; Alizoti, Paraskevi; Bozic, Gregor; Avramidou, Evangelia; Konnert, Monika; Kraigher, Hojka

2016-08-01

Safeguarding sustainability of forest ecosystems with their habitat variability and all their functions is of highest priority. Therefore, the long-term adaptability of forest ecosystems to a changing environment must be secured, e.g., through sustainable forest management. High adaptability is based on biological variation starting at the genetic level. Thus, the ultimate goal of the Convention on Biological Diversity (CBD) to halt the ongoing erosion of biological variation is of utmost importance for forest ecosystem functioning and sustainability. Monitoring of biological diversity over time is needed to detect changes that threaten these biological resources. Genetic variation, as an integral part of biological diversity, needs special attention, and its monitoring can ensure its effective conservation. We compare forest genetic monitoring to other biodiversity monitoring concepts. Forest genetic monitoring (FGM) enables early detection of potentially harmful changes of forest adaptability before these appear at higher biodiversity levels (e.g., species or ecosystem diversity) and can improve the sustainability of applied forest management practices and direct further research. Theoretical genetic monitoring concepts developed up to now need to be evaluated before being implemented on a national and international scale. This article provides an overview of FGM concepts and definitions, discusses their advantages and disadvantages, and provides a flow chart of the steps needed for the optimization and implementation of FGM. FGM is an important module of biodiversity monitoring, and we define an effective FGM scheme as consisting of an assessment of a forest population's capacity to survive, reproduce, and persist under rapid environmental changes on a long-term scale.

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

NASA Astrophysics Data System (ADS)

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

2013-12-01

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

Mutational analysis of vaccinia virus E3 protein: the biological functions do not correlate with its biochemical capacity to bind double-stranded RNA.

PubMed

Dueck, Kevin J; Hu, YuanShen Sandy; Chen, Peter; Deschambault, Yvon; Lee, Jocelyn; Varga, Jessie; Cao, Jingxin

2015-05-01

Vaccinia E3 protein has the biochemical capacity of binding to double-stranded RNA (dsRNA). The best characterized biological functions of the E3 protein include its host range function, suppression of cytokine expression, and inhibition of interferon (IFN)-induced antiviral activity. Currently, the role of the dsRNA binding capacity in the biological functions of the E3 protein is not clear. To further understand the mechanism of the E3 protein biological functions, we performed alanine scanning of the entire dsRNA binding domain of the E3 protein to examine the link between its biochemical capacity of dsRNA binding and biological functions. Of the 115 mutants examined, 20 were defective in dsRNA binding. Although the majority of the mutants defective in dsRNA binding also showed defective replication in HeLa cells, nine mutants (I105A, Y125A, E138A, F148A, F159A, K171A, L182A, L183A, and I187/188A) retained the host range function to various degrees. Further examination of a set of representative E3L mutants showed that residues essential for dsRNA binding are not essential for the biological functions of E3 protein, such as inhibition of protein kinase R (PKR) activation, suppression of cytokine expression, and apoptosis. Thus, data described in this communication strongly indicate the E3 protein performs its biological functions via a novel mechanism which does not correlate with its dsRNA binding activity. dsRNAs produced during virus replication are important pathogen-associated molecular patterns (PAMPs) for inducing antiviral immune responses. One of the strategies used by many viruses to counteract such antiviral immune responses is achieved by producing dsRNA binding proteins, such as poxvirus E3 family proteins, influenza virus NS1, and Ebola virus V35 proteins. The most widely accepted model for the biological functions of this class of viral dsRNA binding proteins is that they bind to and sequester viral dsRNA PAMPs; thus, they suppress the related antiviral immune responses. However, no direct experimental data confirm such a model. In this study of vaccinia E3 protein, we found that the biological functions of the E3 protein are not necessarily linked to its biochemical capacity of dsRNA binding. Thus, our data strongly point to a new concept of virus modulation of cellular antiviral responses triggered by dsRNA PAMPs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Epigenomics and the concept of degeneracy in biological systems

PubMed Central

Mason, Paul H.; Barron, Andrew B.

2014-01-01

Researchers in the field of epigenomics are developing more nuanced understandings of biological complexity, and exploring the multiple pathways that lead to phenotypic expression. The concept of degeneracy—referring to the multiple pathways that a system recruits to achieve functional plasticity—is an important conceptual accompaniment to the growing body of knowledge in epigenomics. Distinct from degradation, redundancy and dilapidation; degeneracy refers to the plasticity of traits whose function overlaps in some environments, but diverges in others. While a redundant system is composed of repeated identical elements performing the same function, a degenerate system is composed of different elements performing similar or overlapping functions. Here, we describe the degenerate structure of gene regulatory systems from the basic genetic code to flexible epigenomic modifications, and discuss how these structural features have contributed to organism complexity, robustness, plasticity and evolvability. PMID:24335757

Development of Nano/Micro Probes for Femtoliter Volume and Single Cell Measurements

NASA Astrophysics Data System (ADS)

Gao, Yang

Single cell analysis has recently emerged as an important field of biomedical re- search. It is now clear that heterogeneity of cell metabolism functions in complex biological systems is correlated to changes in biological function and disease processes. A variety of nano/micro probes were developed to enable investigation of cells properties such as membrane stiffness, pH value. However, very few designs were focused on single cell metabolic function studies. There is a critical need for technologies that provide analysis of heterogeneity of cell metabolic functions, especially on metabolism. Nevertheless, the few existing approaches suffer from fundamental defects and need to be improved. This work focused on developing nano/micro probes that are suitable for single cell functionality investigation. Both types of probes are designed to measure cell-to-cell/time-to-time heterogeneity in metabolic functions over a long period of time. Lab-made carbon nanoprobes were developed especially for electro-physiological measurement. The unique structure of the carbon nanoprobes makes them suitable for important intracellular applications like trans-membrane potential measurements and various electrochemical measurement for cell function studies. While it is important of have ability to carry out intracellular measure, there are also occasions where the information of a cell as a whole is collected. One of the most important indicator of a cells metabolic functions is cell respiration rate/oxygen consumption rate. A micro-perfusion based multi-functional single cell sensing probe was the developed to carry out measurements on cell as a whole. Formed by a double-barrel theta pipette, the perfusion flow enables the direct measurement of the metabolic flux for example oxygen consumption rate. In conclusion, this work developed nano/micro-probes as novel single cell investigation tools. The data acquired from these tools could provide valuable assistance on applications including cell metabolism studies, cancer diagnoses, and therapy evaluations.

Biomimicry in metal-organic materials

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

Zhang, MW; Gu, ZY; Bosch, M

2015-06-15

Nature has evolved a great number of biological molecules which serve as excellent constructional or functional units for metal-organic materials (MOMs). Even though the study of biomimetic MOMs is still at its embryonic stage, considerable progress has been made in the past few years. In this critical review, we will highlight the recent advances in the design, development and application of biomimetic MOMs, and illustrate how the incorporation of biological components into MOMs could further enrich their structural and functional diversity. More importantly, this review will provide a systematic overview of different methods for rational design of MOMs with biomimeticmore » features. Published by Elsevier B.V.« less

Step-by-Step Simulation of Radiation of Radiation Chemistry Using Green Functions for Diffusion-Influenced Reactions

NASA Technical Reports Server (NTRS)

Plante, Ianik; Cucinotta, Francis A.

2011-01-01

The irradiation of biological systems leads to the formation of radiolytic species such as H(raised dot), (raised dot)OH, H2, H2O2, e(sup -)(sub aq), etc.[1]. These species react with neighboring molecules, which result in damage in biological molecules such as DNA. Radiation chemistry is there for every important to understand the radiobiological consequences of radiation[2]. In this work, we discuss an approach based on the exact Green Functions for diffusion-influenced reactions which may be used to simulate radiation chemistry and eventually extended to study more complex systems, including DNA.

Glycobiology of the ocular surface: Mucins and lectins

PubMed Central

Argüeso, Pablo

2013-01-01

Glycosylation is an important and common form of posttranscriptional modification of proteins in cells. A vast array of biological functions has been ascribed to glycans during the last decade thanks to a rapid evolution in glycomic technologies. Glycogenes highly expressed at the human ocular surface include families of glycosyltransferases, proteoglycans, glycan degradation proteins, as well as mucins and carbohydrate-binding proteins such as the galectins. On the apical glycocalyx, mucin O-glycans promote boundary lubrication, prevent bacterial adhesion and endocytic activity, and maintain epithelial barrier function through interactions with galectins. The emerging roles attributed to glycans are contributing to the appreciation of their biological capabilities at the ocular surface. PMID:23325272

Adaptive Neurotechnology for Making Neural Circuits Functional .

NASA Astrophysics Data System (ADS)

Jung, Ranu

2008-03-01

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

The Mediator Complex and Lipid Metabolism.

PubMed

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

2013-03-01

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

Reshaping Plant Biology: Qualitative and Quantitative Descriptors for Plant Morphology

PubMed Central

Balduzzi, Mathilde; Binder, Brad M.; Bucksch, Alexander; Chang, Cynthia; Hong, Lilan; Iyer-Pascuzzi, Anjali S.; Pradal, Christophe; Sparks, Erin E.

2017-01-01

An emerging challenge in plant biology is to develop qualitative and quantitative measures to describe the appearance of plants through the integration of mathematics and biology. A major hurdle in developing these metrics is finding common terminology across fields. In this review, we define approaches for analyzing plant geometry, topology, and shape, and provide examples for how these terms have been and can be applied to plants. In leaf morphological quantifications both geometry and shape have been used to gain insight into leaf function and evolution. For the analysis of cell growth and expansion, we highlight the utility of geometric descriptors for understanding sepal and hypocotyl development. For branched structures, we describe how topology has been applied to quantify root system architecture to lend insight into root function. Lastly, we discuss the importance of using morphological descriptors in ecology to assess how communities interact, function, and respond within different environments. This review aims to provide a basic description of the mathematical principles underlying morphological quantifications. PMID:28217137

Paracrystalline Disorder from Phosphate Ion Orientation and Substitution in Synthetic Bone Mineral.

PubMed

Marisa, Mary E; Zhou, Shiliang; Melot, Brent C; Peaslee, Graham F; Neilson, James R

2016-12-05

Hydroxyapatite is an inorganic mineral closely resembling the mineral phase in bone. However, as a biological mineral, it is highly disordered, and its composition and atomistic structure remain poorly understood. Here, synchrotron X-ray total scattering and pair distribution function analysis methods provide insight into the nature of atomistic disorder in a synthetic bone mineral analogue, chemically substituted hydroxyapatite. By varying the effective hydrolysis rate and/or carbonate concentration during growth of the mineral, compounds with varied degrees of paracrystallinity are prepared. From advanced simulations constrained by the experimental pair distribution function and density functional theory, the paracrystalline disorder prevalent in these materials appears to result from accommodation of carbonate in the lattice through random displacement of the phosphate groups. Though many substitution modalities are likely to occur in concert, the most predominant substitution places carbonate into the mirror plane of an ideal phosphate site. Understanding the mineralogical imperfections of a biologically analogous hydroxyapatite is important not only to potential bone grafting applications but also to biological mineralization processes themselves.

Going mobile: non-cell-autonomous small RNAs shape the genetic landscape of plants.

PubMed

Pyott, Douglas E; Molnar, Attila

2015-04-01

RNA silencing is a form of genetic regulation, which is conserved across eukaryotes and has wide ranging biological functions. Recently, there has been a growing appreciation for the importance of mobility in RNA silencing pathways, particularly in plants. Moreover, in addition to the importance for mobile RNA silencing in an evolutionary context, the potential for utilizing mobile short silencing RNAs in biotechnological applications is becoming apparent. This review aims to set current knowledge of this topic in a historical context and provides examples to illustrate the importance of mobile RNA silencing in both natural and artificially engineered systems in plants. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

A versatile petri net based architecture for modeling and simulation of complex biological processes.

PubMed

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

2004-01-01

The research on modeling and simulation of complex biological systems is getting more important in Systems Biology. In this respect, we have developed Hybrid Function Petri net (HFPN) that was newly developed from existing Petri net because of their intuitive graphical representation and their capabilities for mathematical analyses. However, in the process of modeling metabolic, gene regulatory or signal transduction pathways with the architecture, we have realized three extensions of HFPN, (i) an entity should be extended to contain more than one value, (ii) an entity should be extended to handle other primitive types, e.g. boolean, string, (iii) an entity should be extended to handle more advanced type called object that consists of variables and methods, are necessary for modeling biological systems with Petri net based architecture. To deal with it, we define a new enhanced Petri net called hybrid functional Petri net with extension (HFPNe). To demonstrate the effectiveness of the enhancements, we model and simulate with HFPNe four biological processes that are diffcult to represent with the previous architecture HFPN.

Using cellular automata to generate image representation for biological sequences.

PubMed

Xiao, X; Shao, S; Ding, Y; Huang, Z; Chen, X; Chou, K-C

2005-02-01

A novel approach to visualize biological sequences is developed based on cellular automata (Wolfram, S. Nature 1984, 311, 419-424), a set of discrete dynamical systems in which space and time are discrete. By transforming the symbolic sequence codes into the digital codes, and using some optimal space-time evolvement rules of cellular automata, a biological sequence can be represented by a unique image, the so-called cellular automata image. Many important features, which are originally hidden in a long and complicated biological sequence, can be clearly revealed thru its cellular automata image. With biological sequences entering into databanks rapidly increasing in the post-genomic era, it is anticipated that the cellular automata image will become a very useful vehicle for investigation into their key features, identification of their function, as well as revelation of their "fingerprint". It is anticipated that by using the concept of the pseudo amino acid composition (Chou, K.C. Proteins: Structure, Function, and Genetics, 2001, 43, 246-255), the cellular automata image approach can also be used to improve the quality of predicting protein attributes, such as structural class and subcellular location.

LincRNA-p21: Implications in Human Diseases

PubMed Central

Tang, Sai-Sai; Zheng, Bi-Ying; Xiong, Xing-Dong

2015-01-01

Long noncoding RNAs (lncRNAs), which lack significant protein-coding capacity, regulate various biological processes through diverse and as yet poorly understood molecular mechanisms. However, a number of studies in the past few years have documented important functions for lncRNAs in human diseases. Among these lncRNAs, lincRNA-p21 has been proposed to be a novel regulator of cell proliferation, apoptosis and DNA damage response, and involved in the initiation and progression of human diseases. In this review, we summarize the current knowledge of lincRNA-p21, mainly focus on the known biological functions and its underlying mechanisms. Moreover, we highlight the growing body of evidences for the importance of lincRNA-p21 in diverse human diseases, which indicate lincRNA-p21 as a potential diagnostic marker and/or a valuable therapeutic target for these diseases. PMID:26270659

The multidimensional ionotropic receptors of Drosophila melanogaster.

PubMed

Rimal, S; Lee, Y

2018-02-01

Ionotropic receptors (IRs), which form ion channels, can be categorized into conserved 'antennal IRs', which define the first olfactory receptor family of insects, and species-specific 'divergent IRs', which are expressed in gustatory receptor neurones. These receptors are located primarily in cell bodies and dendrites, and are highly enriched in the tips of the dendritic terminals that convey sensory information to higher brain centres. Antennal IRs play important roles in odour and thermosensation, whereas divergent IRs are involved in other important biological processes such as taste sensation. Some IRs are known to play specific biological roles in the perception of various molecules; however, many of their functions have not yet been defined. Although progress has been made in this field, many functions and mechanisms of these receptors remain unknown. In this review, we provide a comprehensive summary of the current state of knowledge in this field. © 2017 The Royal Entomological Society.

Selection on Network Dynamics Drives Differential Rates of Protein Domain Evolution

PubMed Central

Mannakee, Brian K.; Gutenkunst, Ryan N.

2016-01-01

The long-held principle that functionally important proteins evolve slowly has recently been challenged by studies in mice and yeast showing that the severity of a protein knockout only weakly predicts that protein’s rate of evolution. However, the relevance of these studies to evolutionary changes within proteins is unknown, because amino acid substitutions, unlike knockouts, often only slightly perturb protein activity. To quantify the phenotypic effect of small biochemical perturbations, we developed an approach to use computational systems biology models to measure the influence of individual reaction rate constants on network dynamics. We show that this dynamical influence is predictive of protein domain evolutionary rate within networks in vertebrates and yeast, even after controlling for expression level and breadth, network topology, and knockout effect. Thus, our results not only demonstrate the importance of protein domain function in determining evolutionary rate, but also the power of systems biology modeling to uncover unanticipated evolutionary forces. PMID:27380265

Activity of selected aromatic amino acids in biological systems.

PubMed

Krzyściak, Wirginia

2011-01-01

Besides the structural function in proteins, aromatic amino acids are precursors of many important biological compounds essential for normal functioning of the human organism. Many of these compounds may be used as markers for identification of specific pathological states. Comprehensive knowledge about the metabolism of aromatic amino acids and mechanisms of action of their metabolites made it possible to develop effective treatments for many disorders. However, it should not be forgotten that in some pathological conditions, these compounds could not only be involved in the pathogenesis of many disease entities but could also be used as an important tool in prediction of many diseases. This paper contains a review of published literature on aromatic amino acids in the context of physiological processes of the human body and chosen social disorders, such as cancers; psychiatric disorders: depression, anxiety states, schizophrenia, bipolar affective disorders; neurodegenerative, and cardiovascular diseases; chronic kidney insufficiency or diabetes.

Prediction of interface residue based on the features of residue interaction network.

PubMed

Jiao, Xiong; Ranganathan, Shoba

2017-11-07

Protein-protein interaction plays a crucial role in the cellular biological processes. Interface prediction can improve our understanding of the molecular mechanisms of the related processes and functions. In this work, we propose a classification method to recognize the interface residue based on the features of a weighted residue interaction network. The random forest algorithm is used for the prediction and 16 network parameters and the B-factor are acting as the element of the input feature vector. Compared with other similar work, the method is feasible and effective. The relative importance of these features also be analyzed to identify the key feature for the prediction. Some biological meaning of the important feature is explained. The results of this work can be used for the related work about the structure-function relationship analysis via a residue interaction network model. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integrated Computational Analysis of Genes Associated with Human Hereditary Insensitivity to Pain. A Drug Repurposing Perspective

PubMed Central

Lötsch, Jörn; Lippmann, Catharina; Kringel, Dario; Ultsch, Alfred

2017-01-01

Genes causally involved in human insensitivity to pain provide a unique molecular source of studying the pathophysiology of pain and the development of novel analgesic drugs. The increasing availability of “big data” enables novel research approaches to chronic pain while also requiring novel techniques for data mining and knowledge discovery. We used machine learning to combine the knowledge about n = 20 genes causally involved in human hereditary insensitivity to pain with the knowledge about the functions of thousands of genes. An integrated computational analysis proposed that among the functions of this set of genes, the processes related to nervous system development and to ceramide and sphingosine signaling pathways are particularly important. This is in line with earlier suggestions to use these pathways as therapeutic target in pain. Following identification of the biological processes characterizing hereditary insensitivity to pain, the biological processes were used for a similarity analysis with the functions of n = 4,834 database-queried drugs. Using emergent self-organizing maps, a cluster of n = 22 drugs was identified sharing important functional features with hereditary insensitivity to pain. Several members of this cluster had been implicated in pain in preclinical experiments. Thus, the present concept of machine-learned knowledge discovery for pain research provides biologically plausible results and seems to be suitable for drug discovery by identifying a narrow choice of repurposing candidates, demonstrating that contemporary machine-learned methods offer innovative approaches to knowledge discovery from available evidence. PMID:28848388

Biodiversity, ecosystem functioning, and classical biological control.

PubMed

Evans, Edward W

Increasing concern over worldwide loss of biodiversity has led ecologists to focus intently on how ecosystem functioning may depend on diversity. In applied entomology, there is longstanding interest in the issue, especially as regards the importance of natural enemy diversity for pest control. Here I review parallels in interest, conceptual framework, and conclusions concerning biodiversity as it affects ecosystem functioning in general and classical biological control in particular. Whereas the former focuses on implications of loss of diversity, the latter focuses on implications of increase in diversity as additional species of natural enemies are introduced to novel communities in new geographic regions for insect pest and weed control. Many field studies now demonstrate that ecosystem functioning, e.g., as reflected in primary productivity, is enhanced and stabilized over time by high diversity as the community increases in its efficiency in exploiting available resources. Similarly, there is growing field support for the generalization that increasing species and functional diversity of natural enemies leads to increasing pest suppression. Nonetheless a central concern of classical biological control in particular, as it seeks to minimize non-target effects, remains as to whether one or a few species of natural enemies can provide sufficient pest control.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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. This spatial model constitutes an elegant alternative to voxel-based approaches in neuroimaging studies; not only are their atoms biologically informed, they are also adaptive to high resolutions, represent high dimensions efficiently, and capture long-range spatial dependencies, which are important and challenging objectives for neuroimaging data. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Plant Abiotic Stress Proteomics: The Major Factors Determining Alterations in Cellular Proteome

PubMed Central

Kosová, Klára; Vítámvás, Pavel; Urban, Milan O.; Prášil, Ilja T.; Renaut, Jenny

2018-01-01

HIGHLIGHTS: Major environmental and genetic factors determining stress-related protein abundance are discussed.Major aspects of protein biological function including protein isoforms and PTMs, cellular localization and protein interactions are discussed.Functional diversity of protein isoforms and PTMs is discussed. Abiotic stresses reveal profound impacts on plant proteomes including alterations in protein relative abundance, cellular localization, post-transcriptional and post-translational modifications (PTMs), protein interactions with other protein partners, and, finally, protein biological functions. The main aim of the present review is to discuss the major factors determining stress-related protein accumulation and their final biological functions. A dynamics of stress response including stress acclimation to altered ambient conditions and recovery after the stress treatment is discussed. The results of proteomic studies aimed at a comparison of stress response in plant genotypes differing in stress adaptability reveal constitutively enhanced levels of several stress-related proteins (protective proteins, chaperones, ROS scavenging- and detoxification-related enzymes) in the tolerant genotypes with respect to the susceptible ones. Tolerant genotypes can efficiently adjust energy metabolism to enhanced needs during stress acclimation. Stress tolerance vs. stress susceptibility are relative terms which can reflect different stress-coping strategies depending on the given stress treatment. The role of differential protein isoforms and PTMs with respect to their biological functions in different physiological constraints (cellular compartments and interacting partners) is discussed. The importance of protein functional studies following high-throughput proteome analyses is presented in a broader context of plant biology. In summary, the manuscript tries to provide an overview of the major factors which have to be considered when interpreting data from proteomic studies on stress-treated plants. PMID:29472941

Biological and functional relevance of CASP predictions.

PubMed

Liu, Tianyun; Ish-Shalom, Shirbi; Torng, Wen; Lafita, Aleix; Bock, Christian; Mort, Matthew; Cooper, David N; Bliven, Spencer; Capitani, Guido; Mooney, Sean D; Altman, Russ B

2018-03-01

Our goal is to answer the question: compared with experimental structures, how useful are predicted models for functional annotation? We assessed the functional utility of predicted models by comparing the performances of a suite of methods for functional characterization on the predictions and the experimental structures. We identified 28 sites in 25 protein targets to perform functional assessment. These 28 sites included nine sites with known ligand binding (holo-sites), nine sites that are expected or suggested by experimental authors for small molecule binding (apo-sites), and Ten sites containing important motifs, loops, or key residues with important disease-associated mutations. We evaluated the utility of the predictions by comparing their microenvironments to the experimental structures. Overall structural quality correlates with functional utility. However, the best-ranked predictions (global) may not have the best functional quality (local). Our assessment provides an ability to discriminate between predictions with high structural quality. When assessing ligand-binding sites, most prediction methods have higher performance on apo-sites than holo-sites. Some servers show consistently high performance for certain types of functional sites. Finally, many functional sites are associated with protein-protein interaction. We also analyzed biologically relevant features from the protein assemblies of two targets where the active site spanned the protein-protein interface. For the assembly targets, we find that the features in the models are mainly determined by the choice of template. © 2017 The Authors Proteins: Structure, Function and Bioinformatics Published by Wiley Periodicals, Inc.

Cooperativity to increase Turing pattern space for synthetic biology.

PubMed

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

2015-02-20

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

Combining protein sequence, structure, and dynamics: A novel approach for functional evolution analysis of PAS domain superfamily.

PubMed

Dong, Zheng; Zhou, Hongyu; Tao, Peng

2018-02-01

PAS domains are widespread in archaea, bacteria, and eukaryota, and play important roles in various functions. In this study, we aim to explore functional evolutionary relationship among proteins in the PAS domain superfamily in view of the sequence-structure-dynamics-function relationship. We collected protein sequences and crystal structure data from RCSB Protein Data Bank of the PAS domain superfamily belonging to three biological functions (nucleotide binding, photoreceptor activity, and transferase activity). Protein sequences were aligned and then used to select sequence-conserved residues and build phylogenetic tree. Three-dimensional structure alignment was also applied to obtain structure-conserved residues. The protein dynamics were analyzed using elastic network model (ENM) and validated by molecular dynamics (MD) simulation. The result showed that the proteins with same function could be grouped by sequence similarity, and proteins in different functional groups displayed statistically significant difference in their vibrational patterns. Interestingly, in all three functional groups, conserved amino acid residues identified by sequence and structure conservation analysis generally have a lower fluctuation than other residues. In addition, the fluctuation of conserved residues in each biological function group was strongly correlated with the corresponding biological function. This research suggested a direct connection in which the protein sequences were related to various functions through structural dynamics. This is a new attempt to delineate functional evolution of proteins using the integrated information of sequence, structure, and dynamics. © 2017 The Protein Society.

The contribution of early language development to children's emotional and behavioural functioning at 6 years: an analysis of data from the Children in Focus sample from the ALSPAC birth cohort.

PubMed

Clegg, Judy; Law, James; Rush, Robert; Peters, Tim J; Roulstone, Susan

2015-01-01

An association between children's early language development and their emotional and behavioural functioning is reported in the literature. The nature of the association remains unclear and it has not been established if such an association is found in a population-based cohort in addition to clinical populations. This study examines the reported association between language development and emotional and behavioural functioning in a population-based cohort. Data from 1,314 children in the Children in Focus (CiF) sample from the Avon Longitudinal Study of Parents and Children (ALSPAC) were analysed. Regression models identified the extent to which early language ability at 2 years of age and later language ability at 4 years of age is associated with emotional and behavioural functioning at 6 years while accounting for biological and social risk and adjusting for age and performance intelligence (PIQ). A series of univariable and multivariable analyses identified a strong influence of biological risk, social risk and early and later language ability to emotional and behavioural functioning. Interestingly, social risk dropped out of the multivariate analyses when age and PIQ were controlled for. Early expressive vocabulary at 2 years and receptive language at 4 years made a strong contribution to emotional and behavioural functioning at 6 years in addition to biological risk. The final model accounted for 11.6% of the variance in emotional and behavioural functioning at 6 years. The study identified that early language ability at 2 years, specifically expressive vocabulary and later receptive language at 4 years both made a moderate, but important contribution to emotional and behavioural functioning at 6 years of age. Although children's language development is important in understanding children's emotional and behavioural functioning, the study shows that it is one of many developmental factors involved. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

Artificial Synaptic Devices Based on Natural Chicken Albumen Coupled Electric-Double-Layer Transistors

NASA Astrophysics Data System (ADS)

Wu, Guodong; Feng, Ping; Wan, Xiang; Zhu, Liqiang; Shi, Yi; Wan, Qing

2016-03-01

Recent progress in using biomaterials to fabricate functional electronics has got growing attention for the new generation of environmentally friendly and biocompatible electronic devices. As a kind of biological material with rich source, proteins are essential natural component of all organisms. At the same time, artificial synaptic devices are of great significance for neuromorphic systems because they can emulate the signal process and memory behaviors of biological synapses. In this report, natural chicken albumen with high proton conductivity was used as the coupling electrolyte film for organic/inorganic hybrid synaptic devices fabrication. Some important synaptic functions including paired-pulse facilitation, dynamic filtering, short-term to long-term memory transition and spatial summation and shunting inhibition were successfully mimicked. Our results are very interesting for biological friendly artificial neuron networks and neuromorphic systems.

Gene networks, occlusal clocks, and functional patches: new understanding of pattern and process in the evolution of the dentition.

PubMed

Polly, P David

2015-05-01

Our understanding of the evolution of the dentition has been transformed by advances in the developmental biology, genetics, and functional morphology of teeth, as well as the methods available for studying tooth form and function. The hierarchical complexity of dental developmental genetics combined with dynamic effects of cells and tissues during development allow for substantial, rapid, and potentially non-linear evolutionary changes. Studies of selection on tooth function in the wild and evolutionary functional comparisons both suggest that tooth function and adaptation to diets are the most important factors guiding the evolution of teeth, yet selection against random changes that produce malocclusions (selectional drift) may be an equally important factor in groups with tribosphenic dentitions. These advances are critically reviewed here.

Holistic systems biology approaches to molecular mechanisms of human helper T cell differentiation to functionally distinct subsets.

PubMed

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.

Positive affect and psychobiological processes

PubMed Central

Dockray, Samantha; Steptoe, Andrew

2010-01-01

Positive affect has been associated with favourable health outcomes, and it is likely that several biological processes mediate the effects of positive mood on physical health. There is converging evidence that positive affect activates the neuroendocrine, autonomic and immune systems in distinct and functionally meaningful ways. Cortisol, both total output and the awakening response, has consistently been shown to be lower among individuals with higher levels of positive affect. The beneficial effects of positive mood on cardiovascular function, including heart rate and blood pressure, and the immune system have also been described. The influence of positive affect on these psychobiological processes are independent of negative affect, suggesting that positive affect may have characteristic biological correlates. The duration and conceptualisation of positive affect may be important considerations in understanding how different biological systems are activated in association with positive affect. The association of positive affect and psychobiological processes has been established, and these biological correlates may be partly responsible for the protective effects of positive affect on health outcomes. PMID:20097225

Fungal biology and agriculture: revisiting the field

USGS Publications Warehouse

Yarden, O.; Ebbole, D.J.; Freeman, S.; Rodriguez, R.J.; Dickman, M. B.

2003-01-01

Plant pathology has made significant progress over the years, a process that involved overcoming a variety of conceptual and technological hurdles. Descriptive mycology and the advent of chemical plant-disease management have been followed by biochemical and physiological studies of fungi and their hosts. The later establishment of biochemical genetics along with the introduction of DNA-mediated transformation have set the stage for dissection of gene function and advances in our understanding of fungal cell biology and plant-fungus interactions. Currently, with the advent of high-throughput technologies, we have the capacity to acquire vast data sets that have direct relevance to the numerous subdisciplines within fungal biology and pathology. These data provide unique opportunities for basic research and for engineering solutions to important agricultural problems. However, we also are faced with the challenge of data organization and mining to analyze the relationships between fungal and plant genomes and to elucidate the physiological function of pertinent DNA sequences. We present our perspective of fungal biology and agriculture, including administrative and political challenges to plant protection research.

Approaching an experimental electron density model of the biologically active trans -epoxysuccinyl amide group-Substituent effects vs. crystal packing

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

Shi, Ming W.; Stewart, Scott G.; Sobolev, Alexandre N.

The trans-epoxysuccinyl amide group as a biologically active moiety in cysteine protease inhibitors such as loxistatin acid E64c has been used as a benchmark system for theoretical studies of environmental effects on the electron density of small active ingredients in relation to their biological activity. Here, the synthesis and the electronic properties of the smallest possible active site model compound are reported to close the gap between the unknown experimental electron density of trans-epoxysuccinyl amides and the well-known function of related drugs. Intramolecular substituent effects are separated from intermolecular crystal packing effects on the electron density, which allows us tomore » predict the conditions under which an experimental electron density investigation on trans-epoxysuccinyl amides will be possible. In this context, the special importance of the carboxylic acid function in the model compound for both crystal packing and biological activity is revealed through the novel tool of model energy analysis.« less

Stochasticity versus determinism: consequences for realistic gene regulatory network modelling and evolution.

PubMed

Jenkins, Dafyd J; Stekel, Dov J

2010-02-01

Gene regulation is one important mechanism in producing observed phenotypes and heterogeneity. Consequently, the study of gene regulatory network (GRN) architecture, function and evolution now forms a major part of modern biology. However, it is impossible to experimentally observe the evolution of GRNs on the timescales on which living species evolve. In silico evolution provides an approach to studying the long-term evolution of GRNs, but many models have either considered network architecture from non-adaptive evolution, or evolution to non-biological objectives. Here, we address a number of important modelling and biological questions about the evolution of GRNs to the realistic goal of biomass production. Can different commonly used simulation paradigms, in particular deterministic and stochastic Boolean networks, with and without basal gene expression, be used to compare adaptive with non-adaptive evolution of GRNs? Are these paradigms together with this goal sufficient to generate a range of solutions? Will the interaction between a biological goal and evolutionary dynamics produce trade-offs between growth and mutational robustness? We show that stochastic basal gene expression forces shrinkage of genomes due to energetic constraints and is a prerequisite for some solutions. In systems that are able to evolve rates of basal expression, two optima, one with and one without basal expression, are observed. Simulation paradigms without basal expression generate bloated networks with non-functional elements. Further, a range of functional solutions was observed under identical conditions only in stochastic networks. Moreover, there are trade-offs between efficiency and yield, indicating an inherent intertwining of fitness and evolutionary dynamics.

Recent advances in stable isotope labeling based techniques for proteome relative quantification.

PubMed

Zhou, Yuan; Shan, Yichu; Zhang, Lihua; Zhang, Yukui

2014-10-24

The large scale relative quantification of all proteins expressed in biological samples under different states is of great importance for discovering proteins with important biological functions, as well as screening disease related biomarkers and drug targets. Therefore, the accurate quantification of proteins at proteome level has become one of the key issues in protein science. Herein, the recent advances in stable isotope labeling based techniques for proteome relative quantification were reviewed, from the aspects of metabolic labeling, chemical labeling and enzyme-catalyzed labeling. Furthermore, the future research direction in this field was prospected. Copyright © 2014 Elsevier B.V. All rights reserved.

Nonlinear dynamics based digital logic and circuits.

PubMed

Kia, Behnam; Lindner, John F; Ditto, William L

2015-01-01

We discuss the role and importance of dynamics in the brain and biological neural networks and argue that dynamics is one of the main missing elements in conventional Boolean logic and circuits. We summarize a simple dynamics based computing method, and categorize different techniques that we have introduced to realize logic, functionality, and programmability. We discuss the role and importance of coupled dynamics in networks of biological excitable cells, and then review our simple coupled dynamics based method for computing. In this paper, for the first time, we show how dynamics can be used and programmed to implement computation in any given base, including but not limited to base two.

The aims of systems biology: between molecules and organisms.

PubMed

Noble, D

2011-05-01

The systems approach to biology has a long history. Its recent rapid resurgence at the turn of the century reflects the problems encountered in interpreting the sequencing of the genome and the failure of that immense achievement to provide rapid and direct solutions to major multi-factorial diseases. This paper argues that systems biology is necessarily multilevel and that there is no privileged level of causality in biological systems. It is an approach rather than a separate discipline. Functionality arises from biological networks that interact with the genome, the environment and the phenotype. This view of biology is very different from the gene-centred views of neo-Darwinism and molecular biology. In neuroscience, the systems approach leads naturally to 2 important conclusions: first, that the idea of 'programs' in the brain is confusing, and second, that the self is better interpreted as a process than as an object. © Georg Thieme Verlag KG Stuttgart · New York.

Optical sensor for heat conduction measurement in biological tissue

NASA Astrophysics Data System (ADS)

Gutierrez-Arroyo, A.; Sanchez-Perez, C.; Aleman-Garcia, N.

2013-06-01

This paper presents the design of a heat flux sensor using an optical fiber system to measure heat conduction in biological tissues. This optoelectronic device is based on the photothermal beam deflection of a laser beam travelling in an acrylic slab this deflection is measured with a fiber optic angle sensor. We measure heat conduction in biological samples with high repeatability and sensitivity enough to detect differences in tissues from three chicken organs. This technique could provide important information of vital organ function as well as the detect modifications due to degenerative diseases or physical damage caused by medications or therapies.

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

PubMed Central

Sun, Miao

2015-01-01

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

[Biology and immunotherapy advance of interleukin 2 and interleukin 15-review].

PubMed

Chen, Guang-Hua; Wu, De-Pei

2009-08-01

IL-2 and IL-15 play an important roles in regulating the lymphocyte function and homeostasis. Advances in understanding of the cellular and molecular biology of IL-2 and IL-15 and their receptor complex have provided rationale to better utilize them to expand and activate immune effectors in patients with cancer. These two cytokines stimulate similar responses from lymphocytes in vitro, but play markedly distinct roles in lymphoid biology in vivo. Their distinct physiological functions can be ascribed to distinct signaling pathways initiated by distinct cytokine receptor subunits, differential expression patterns of their receptors. Recently, the discovery of a novel mechanism of IL-15 cytokine signaling, trans-presentation, has provided insights into the divergent ways of these cytokine function. Although their heterotrimeric receptors have two receptor subunits in common, these two cytokines have contrasting roles in adaptive immune responses. The unique role of interleukin 2 is in the elimination of self-reactive T cells to prevent autoimmunity. By contrast, interleukin 15 is dedicated to the prolonged maintenance of memory T-cell responses to pathogens. As discussed in this article, the biology of IL-2 and IL-15 two cytokines will affect the development of novel treatment for malignancies and autoimmune diseases.

Structural and Chemical Biology of Terpenoid Cyclases

PubMed Central

2017-01-01

The year 2017 marks the twentieth anniversary of terpenoid cyclase structural biology: a trio of terpenoid cyclase structures reported together in 1997 were the first to set the foundation for understanding the enzymes largely responsible for the exquisite chemodiversity of more than 80000 terpenoid natural products. Terpenoid cyclases catalyze the most complex chemical reactions in biology, in that more than half of the substrate carbon atoms undergo changes in bonding and hybridization during a single enzyme-catalyzed cyclization reaction. The past two decades have witnessed structural, functional, and computational studies illuminating the modes of substrate activation that initiate the cyclization cascade, the management and manipulation of high-energy carbocation intermediates that propagate the cyclization cascade, and the chemical strategies that terminate the cyclization cascade. The role of the terpenoid cyclase as a template for catalysis is paramount to its function, and protein engineering can be used to reprogram the cyclization cascade to generate alternative and commercially important products. Here, I review key advances in terpenoid cyclase structural and chemical biology, focusing mainly on terpenoid cyclases and related prenyltransferases for which X-ray crystal structures have informed and advanced our understanding of enzyme structure and function. PMID:28841019

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

PubMed

Sun, Miao; Kraus, W Lee

2015-02-01

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

Characterization of the stability and bio-functionality of tethered proteins on bioengineered scaffolds: implications for stem cell biology and tissue repair.

PubMed

Wang, Ting-Yi; Bruggeman, Kiara A F; Sheean, Rebecca K; Turner, Bradley J; Nisbet, David R; Parish, Clare L

2014-05-23

Various engineering applications have been utilized to deliver molecules and compounds in both innate and biological settings. In the context of biological applications, the timely delivery of molecules can be critical for cellular and organ function. As such, previous studies have demonstrated the superiority of long-term protein delivery, by way of protein tethering onto bioengineered scaffolds, compared with conventional delivery of soluble protein in vitro and in vivo. Despite such benefits little knowledge exists regarding the stability, release kinetics, longevity, activation of intracellular pathway, and functionality of these proteins over time. By way of example, here we examined the stability, degradation and functionality of a protein, glial-derived neurotrophic factor (GDNF), which is known to influence neuronal survival, differentiation, and neurite morphogenesis. Enzyme-linked immunosorbent assays (ELISA) revealed that GDNF, covalently tethered onto polycaprolactone (PCL) electrospun nanofibrous scaffolds, remained present on the scaffold surface for 120 days, with no evidence of protein leaching or degradation. The tethered GDNF protein remained functional and capable of activating downstream signaling cascades, as revealed by its capacity to phosphorylate intracellular Erk in a neural cell line. Furthermore, immobilization of GDNF protein promoted cell survival and differentiation in culture at both 3 and 7 days, further validating prolonged functionality of the protein, well beyond the minutes to hours timeframe observed for soluble proteins under the same culture conditions. This study provides important evidence of the stability and functionality kinetics of tethered molecules. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Lessons from (patho)physiological tissue stiffness and their implications for drug screening, drug delivery and regenerative medicine.

PubMed

Chen, Wen Li Kelly; Simmons, Craig A

2011-04-30

Diseased tissues are noted for their compromised mechanical properties, which contribute to organ failure; regeneration entails restoration of tissue structure and thereby functions. Thus, the physical signature of a tissue is closely associated with its biological function. In this review, we consider a mechanics-centric view of disease and regeneration by drawing parallels between in vivo tissue-level observations and corroborative cellular evidence in vitro to demonstrate the importance of the mechanical stiffness of the extracellular matrix in these processes. This is not intended to devalue the importance of biochemical signaling; in fact, as we discuss, many mechanical stiffness-driven processes not only require cooperation with biochemical cues, but they ultimately converge at common signaling cascades to influence cell and tissue function in an integrative manner. The study of how physical and biochemical signals collectively modulate cell function not only brings forth a more holistic understanding of cell (patho)biology, but it also creates opportunities to control material properties to improve culture platforms for research and drug screening and aid in the rationale design of biomaterials for molecular therapy and tissue engineering applications. Copyright © 2011 Elsevier B.V. All rights reserved.

Abundance and Distribution of Geographically Isolated Wetlands across the Conterminous United States

EPA Science Inventory

Geographically isolated wetlands (GIWS) are important landscape elements involved in hydrologic, biogeochemical, and biological functioning. Their influence, under certain circumstances, can significantly affect other waters of the Unites States. However, there have been no data-...

CommWalker: correctly evaluating modules in molecular networks in light of annotation bias.

PubMed

Luecken, M D; Page, M J T; Crosby, A J; Mason, S; Reinert, G; Deane, C M

2018-03-15

Detecting novel functional modules in molecular networks is an important step in biological research. In the absence of gold standard functional modules, functional annotations are often used to verify whether detected modules/communities have biological meaning. However, as we show, the uneven distribution of functional annotations means that such evaluation methods favor communities of well-studied proteins. We propose a novel framework for the evaluation of communities as functional modules. Our proposed framework, CommWalker, takes communities as inputs and evaluates them in their local network environment by performing short random walks. We test CommWalker's ability to overcome annotation bias using input communities from four community detection methods on two protein interaction networks. We find that modules accepted by CommWalker are similarly co-expressed as those accepted by current methods. Crucially, CommWalker performs well not only in well-annotated regions, but also in regions otherwise obscured by poor annotation. CommWalker community prioritization both faithfully captures well-validated communities and identifies functional modules that may correspond to more novel biology. The CommWalker algorithm is freely available at opig.stats.ox.ac.uk/resources or as a docker image on the Docker Hub at hub.docker.com/r/lueckenmd/commwalker/. deane@stats.ox.ac.uk. Supplementary data are available at Bioinformatics online.

Importance of N-Glycosylation on CD147 for Its Biological Functions

PubMed Central

Bai, Yang; Huang, Wan; Ma, Li-Tian; Jiang, Jian-Li; Chen, Zhi-Nan

2014-01-01

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. PMID:24739808

Light and Dark of Reactive Oxygen Species for Vascular Function: 2014 ASVB (Asian Society of Vascular Biology).

PubMed

Shimokawa, Hiroaki; Satoh, Kimio

2015-05-01

Vascular-derived hydrogen peroxide (H2O2) serves as an important signaling molecule in the cardiovascular system and contributes to vascular homeostasis. H2O2 is a second messenger, transducing the oxidative signal into biological responses through posttranslational protein modification. The balance between oxidant and antioxidant systems regulates intracellular redox status, and their imbalance causes oxidative or reductive stress, leading to cellular damage in cardiovascular systems. Excessive H2O2 deteriorates vascular functions and promotes vascular disease through multiple pathways. The RhoA/Rho-kinase pathway plays an important role in various fundamental cellular functions, including production of excessive reactive oxygen species, leading to the development of cardiovascular diseases. Rho-kinase (ROCK1 and ROCK2) belongs to the family of serine/threonine kinases and is an important downstream effector of the small GTP-binding protein RhoA. Rho-kinase plays a crucial role in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, stroke, and heart failure. Thus, Rho-kinase inhibitors may be useful for the treatment of cardiovascular diseases in humans. In this review, we will briefly discuss the roles of vascular-derived H2O2 and review the recent progress in the translational research on the therapeutic importance of the Rho-kinase pathway in cardiovascular medicine.

New scaling relation for information transfer in biological networks

PubMed Central

Kim, Hyunju; Davies, Paul; Walker, Sara Imari

2015-01-01

We quantify characteristics of the informational architecture of two representative biological networks: the Boolean network model for the cell-cycle regulatory network of the fission yeast Schizosaccharomyces pombe (Davidich et al. 2008 PLoS ONE 3, e1672 (doi:10.1371/journal.pone.0001672)) and that of the budding yeast Saccharomyces cerevisiae (Li et al. 2004 Proc. Natl Acad. Sci. USA 101, 4781–4786 (doi:10.1073/pnas.0305937101)). We compare our results for these biological networks with the same analysis performed on ensembles of two different types of random networks: Erdös–Rényi and scale-free. We show that both biological networks share features in common that are not shared by either random network ensemble. In particular, the biological networks in our study process more information than the random networks on average. Both biological networks also exhibit a scaling relation in information transferred between nodes that distinguishes them from random, where the biological networks stand out as distinct even when compared with random networks that share important topological properties, such as degree distribution, with the biological network. We show that the most biologically distinct regime of this scaling relation is associated with a subset of control nodes that regulate the dynamics and function of each respective biological network. Information processing in biological networks is therefore interpreted as an emergent property of topology (causal structure) and dynamics (function). Our results demonstrate quantitatively how the informational architecture of biologically evolved networks can distinguish them from other classes of network architecture that do not share the same informational properties. PMID:26701883

Evolution and function of CAG/polyglutamine repeats in protein–protein interaction networks

PubMed Central

Schaefer, Martin H.; Wanker, Erich E.; Andrade-Navarro, Miguel A.

2012-01-01

Expanded runs of consecutive trinucleotide CAG repeats encoding polyglutamine (polyQ) stretches are observed in the genes of a large number of patients with different genetic diseases such as Huntington's and several Ataxias. Protein aggregation, which is a key feature of most of these diseases, is thought to be triggered by these expanded polyQ sequences in disease-related proteins. However, polyQ tracts are a normal feature of many human proteins, suggesting that they have an important cellular function. To clarify the potential function of polyQ repeats in biological systems, we systematically analyzed available information stored in sequence and protein interaction databases. By integrating genomic, phylogenetic, protein interaction network and functional information, we obtained evidence that polyQ tracts in proteins stabilize protein interactions. This happens most likely through structural changes whereby the polyQ sequence extends a neighboring coiled-coil region to facilitate its interaction with a coiled-coil region in another protein. Alteration of this important biological function due to polyQ expansion results in gain of abnormal interactions, leading to pathological effects like protein aggregation. Our analyses suggest that research on polyQ proteins should shift focus from expanded polyQ proteins into the characterization of the influence of the wild-type polyQ on protein interactions. PMID:22287626

Molecular Force Spectroscopy on Cells

NASA Astrophysics Data System (ADS)

Liu, Baoyu; Chen, Wei; Zhu, Cheng

2015-04-01

Molecular force spectroscopy has become a powerful tool to study how mechanics regulates biology, especially the mechanical regulation of molecular interactions and its impact on cellular functions. This force-driven methodology has uncovered a wealth of new information of the physical chemistry of molecular bonds for various biological systems. The new concepts, qualitative and quantitative measures describing bond behavior under force, and structural bases underlying these phenomena have substantially advanced our fundamental understanding of the inner workings of biological systems from the nanoscale (molecule) to the microscale (cell), elucidated basic molecular mechanisms of a wide range of important biological processes, and provided opportunities for engineering applications. Here, we review major force spectroscopic assays, conceptual developments of mechanically regulated kinetics of molecular interactions, and their biological relevance. We also present current challenges and highlight future directions.

Biological determination of mental disorders: a discussion based on recent hypotheses from neuroscience.

PubMed

Freitas-Silva, Luna Rodrigues; Ortega, Francisco

2016-08-29

Understanding the processes involved in the development of mental disorders has proven challenging ever since psychiatry was founded as a field. Neuroscience has provided new expectations that an explanation will be found for the development of mental disorders based on biological functioning alone. However, such a goal has not been that easy to achieve, and new hypotheses have begun to appear in neuroscience research. In this article we identify epigenetics, neurodevelopment, and plasticity as the principal avenues for a new understanding of the biology of mental phenomena. Genetic complexity, the environment's formative role, and variations in vulnerability involve important changes in the principal hypotheses on biological determination of mental disorders, suggesting a reconfiguration of the limits between the "social" and the "biological" in neuroscience research.

Biosynthesis and biological functions of terpenoids in plants.

PubMed

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.

Biological soil crusts: Diminutive communities of potential global importance

USGS Publications Warehouse

Ferrenberg, Scott; Tucker, Colin; Reed, Sasha C.

2017-01-01

Biological soil crusts (biocrusts) are widespread, diverse communities of cyanobacteria, fungi, lichens, and mosses living on soil surfaces, primarily in drylands. Biocrusts can locally govern primary production, soil fertility, hydrology, and surface energy balance, with considerable variation in these functions across alternate community states. Further, these communities have been implicated in Earth system functioning via potential influences on global biogeochemistry and climate. Biocrusts are easily destroyed by disturbances and appear to be exceptionally vulnerable to warming temperatures and altered precipitation inputs, signaling possible losses of dryland functions with global change. Despite these concerns, we lack sufficient spatiotemporal data on biocrust function, cover, and community structure to confidently assess their ecological roles across the extensive dryland biome. Here, we present the case for cross-scale research and restoration efforts coupled with remote-sensing and modeling approaches that improve our collective understanding of biocrust responses to global change and the ecological roles of these diminutive communities at global scales.

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

PubMed

Spinella, Rosaria; Sawhney, Rohit; Jalan, Rajiv

2016-01-01

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

Cyclic and Linear Monoterpenes in Phospholipid Membranes: Phase Behavior, Bilayer Structure, and Molecular Dynamics.

PubMed

Pham, Quoc Dat; Topgaard, Daniel; Sparr, Emma

2015-10-13

Monoterpenes are abundant in essential oils extracted from plants. These relatively small and hydrophobic molecules have shown important biological functions, including antimicrobial activity and membrane penetration enhancement. The interaction between the monoterpenes and lipid bilayers is considered important to the understanding of the biological functions of monoterpenes. In this study, we investigated the effect of cyclic and linear monoterpenes on the structure and dynamics of lipids in model membranes. We have studied the ternary system 1,2-dimyristoyl-sn-glycero-3-phosphocholine-monoterpene-water as a model with a focus on dehydrated conditions. By combining complementary techniques, including differential scanning calorimetry, solid-state nuclear magnetic resonance, and small- and wide-angle X-ray scattering, bilayer structure, phase transitions, and lipid molecular dynamics were investigated at different water contents. Monoterpenes cause pronounced melting point depression and phase segregation in lipid bilayers, and the extent of these effects depends on the hydration conditions. The addition of a small amount of thymol to the fluid bilayer (volume fraction of 0.03 in the bilayer) leads to an increased order in the acyl chain close to the bilayer interface. The findings are discussed in relation to biological systems and lipid formulations.

Correlated evolution of thermal niches and functional physiology in tropical freshwater fishes.

PubMed

Culumber, Zachary W; Tobler, Michael

2018-05-01

The role of ecology in phenotypic and species diversification is widely documented. Nonetheless, numerous nonadaptive processes can shape realized niches and phenotypic variation in natural populations, complicating inferences about adaptive evolution at macroevolutionary scales. We tested for evolved differences in thermal tolerances and their association with the realized thermal niche (including metrics describing diurnal and seasonal patterns of temperature extremes and variability) across a genus of tropical freshwater fishes reared in a standardized environment. There was limited evolution along the thermal niche axis associated with variation in maximum temperature and in upper thermal limits. In contrast, there was considerable diversification along the first major axis of the thermal niche associated with minimum temperatures and in lower thermal limits. Across our adaptive landscape analyses, 70% of species exhibited evidence of divergence in thermal niches. Most importantly, the first two major axes of thermal niche variation were significantly correlated with variation in lower thermal limits. Our results indicate adaptation to divergent thermal niches and adaptive evolution of related functional traits, and highlight the importance of divergence in lower thermal limits for the evolution of tropical biodiversity. © 2018 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2018 European Society For Evolutionary Biology.

Scaffolding Function of PI3Kgamma Emerges from Enzyme's Shadow.

PubMed

Mohan, Maradumane L; Naga Prasad, Sathyamangla V

2017-03-24

Traditionally, an enzyme is a protein that mediates biochemical action by binding to the substrate and by catalyzing the reaction that translates external cues into biological responses. Sequential dissemination of information from one enzyme to another facilitates signal transduction in biological systems providing for feed-forward and feed-back mechanisms. Given this viewpoint, an enzyme without its catalytic activity is generally considered to be an inert organizational protein without catalytic function and has classically been termed as pseudo-enzymes. However, pseudo-enzymes still have biological function albeit non-enzymatic like serving as a chaperone protein or an interactive platform between proteins. In this regard, majority of the studies have focused solely on the catalytic role of enzymes in biological function, overlooking the potentially critical non-enzymatic roles. Increasing evidence from recent studies implicate that the scaffolding function of enzymes could be as important in signal transduction as its catalytic activity, which is an antithesis to the definition of enzymes. Recognition of non-enzymatic functions could be critical, as these unappreciated roles may hold clues to the ineffectiveness of kinase inhibitors in pathology, which is characteristically associated with increased enzyme expression. Using an established enzyme phosphoinositide 3-kinase γ, we discuss the insights obtained from the scaffolding function and how this non-canonical role could contribute to/alter the outcomes in pathology like cancer and heart failure. Also, we hope that with this review, we provide a forum and a starting point to discuss the idea that catalytic function alone may not account for all the actions observed with increased expression of the enzyme. Copyright © 2017 Elsevier Ltd. All rights reserved.

Simulating biological processes: stochastic physics from whole cells to colonies.

PubMed

Earnest, Tyler M; Cole, John A; Luthey-Schulten, Zaida

2018-05-01

The last few decades have revealed the living cell to be a crowded spatially heterogeneous space teeming with biomolecules whose concentrations and activities are governed by intrinsically random forces. It is from this randomness, however, that a vast array of precisely timed and intricately coordinated biological functions emerge that give rise to the complex forms and behaviors we see in the biosphere around us. This seemingly paradoxical nature of life has drawn the interest of an increasing number of physicists, and recent years have seen stochastic modeling grow into a major subdiscipline within biological physics. Here we review some of the major advances that have shaped our understanding of stochasticity in biology. We begin with some historical context, outlining a string of important experimental results that motivated the development of stochastic modeling. We then embark upon a fairly rigorous treatment of the simulation methods that are currently available for the treatment of stochastic biological models, with an eye toward comparing and contrasting their realms of applicability, and the care that must be taken when parameterizing them. Following that, we describe how stochasticity impacts several key biological functions, including transcription, translation, ribosome biogenesis, chromosome replication, and metabolism, before considering how the functions may be coupled into a comprehensive model of a 'minimal cell'. Finally, we close with our expectation for the future of the field, focusing on how mesoscopic stochastic methods may be augmented with atomic-scale molecular modeling approaches in order to understand life across a range of length and time scales.

Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold.

PubMed

Berman, Dora M; Molano, R Damaris; Fotino, Carmen; Ulissi, Ulisse; Gimeno, Jennifer; Mendez, Armando J; Kenyon, Norman M; Kenyon, Norma S; Andrews, David M; Ricordi, Camillo; Pileggi, Antonello

2016-05-01

Transplantation of pancreatic islets is a therapeutic option to preserve or restore β-cell function. Our study was aimed at developing a clinically applicable protocol for extrahepatic transplantation of pancreatic islets. The potency of islets implanted onto the omentum, using an in situ-generated adherent, resorbable plasma-thrombin biologic scaffold, was evaluated in diabetic rat and nonhuman primate (NHP) models. Intraomental islet engraftment in the biologic scaffold was confirmed by achievement of improved metabolic function and preservation of islet cytoarchitecture, with reconstitution of rich intrainsular vascular networks in both species. Long-term nonfasting normoglycemia and adequate glucose clearance (tolerance tests) were achieved in both intrahepatic and intraomental sites in rats. Intraomental graft recipients displayed lower levels of serum biomarkers of islet distress (e.g., acute serum insulin) and inflammation (e.g., leptin and α2-macroglobulin). Importantly, low-purity (30:70% endocrine:exocrine) syngeneic rat islet preparations displayed function equivalent to that of pure (>95% endocrine) preparations after intraomental biologic scaffold implantation. Moreover, the biologic scaffold sustained allogeneic islet engraftment in immunosuppressed recipients. Collectively, our feasibility/efficacy data, along with the simplicity of the procedure and the safety of the biologic scaffold components, represented sufficient preclinical testing to proceed to a pilot phase I/II clinical trial. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Simulating biological processes: stochastic physics from whole cells to colonies

NASA Astrophysics Data System (ADS)

Earnest, Tyler M.; Cole, John A.; Luthey-Schulten, Zaida

2018-05-01

The last few decades have revealed the living cell to be a crowded spatially heterogeneous space teeming with biomolecules whose concentrations and activities are governed by intrinsically random forces. It is from this randomness, however, that a vast array of precisely timed and intricately coordinated biological functions emerge that give rise to the complex forms and behaviors we see in the biosphere around us. This seemingly paradoxical nature of life has drawn the interest of an increasing number of physicists, and recent years have seen stochastic modeling grow into a major subdiscipline within biological physics. Here we review some of the major advances that have shaped our understanding of stochasticity in biology. We begin with some historical context, outlining a string of important experimental results that motivated the development of stochastic modeling. We then embark upon a fairly rigorous treatment of the simulation methods that are currently available for the treatment of stochastic biological models, with an eye toward comparing and contrasting their realms of applicability, and the care that must be taken when parameterizing them. Following that, we describe how stochasticity impacts several key biological functions, including transcription, translation, ribosome biogenesis, chromosome replication, and metabolism, before considering how the functions may be coupled into a comprehensive model of a ‘minimal cell’. Finally, we close with our expectation for the future of the field, focusing on how mesoscopic stochastic methods may be augmented with atomic-scale molecular modeling approaches in order to understand life across a range of length and time scales.

Cheering for Team Science | Office of Cancer Genomics

Cancer.gov

As a graduate student, my PhD thesis focused on the function of a single human gene, within a genome of some 20,000 genes. Although this sometimes made my work seem insignificant, I was reminded of how important one small piece of a large puzzle can be when I discovered all the ways the gene knockout cells were disadvantaged. Studying the basic biology of our cells made me appreciate the beautiful complexity of human biology.

Preclinical Magnetic Resonance Imaging and Systems Biology in Cancer Research

PubMed Central

Albanese, Chris; Rodriguez, Olga C.; VanMeter, John; Fricke, Stanley T.; Rood, Brian R.; Lee, YiChien; Wang, Sean S.; Madhavan, Subha; Gusev, Yuriy; Petricoin, Emanuel F.; Wang, Yue

2014-01-01

Biologically accurate mouse models of human cancer have become important tools for the study of human disease. The anatomical location of various target organs, such as brain, pancreas, and prostate, makes determination of disease status difficult. Imaging modalities, such as magnetic resonance imaging, can greatly enhance diagnosis, and longitudinal imaging of tumor progression is an important source of experimental data. Even in models where the tumors arise in areas that permit visual determination of tumorigenesis, longitudinal anatomical and functional imaging can enhance the scope of studies by facilitating the assessment of biological alterations, (such as changes in angiogenesis, metabolism, cellular invasion) as well as tissue perfusion and diffusion. One of the challenges in preclinical imaging is the development of infrastructural platforms required for integrating in vivo imaging and therapeutic response data with ex vivo pathological and molecular data using a more systems-based multiscale modeling approach. Further challenges exist in integrating these data for computational modeling to better understand the pathobiology of cancer and to better affect its cure. We review the current applications of preclinical imaging and discuss the implications of applying functional imaging to visualize cancer progression and treatment. Finally, we provide new data from an ongoing preclinical drug study demonstrating how multiscale modeling can lead to a more comprehensive understanding of cancer biology and therapy. PMID:23219428

[The Functional Role of Exosomes in Cancer Biology and Their Potential as Biomarkers and Therapeutic Targets of Cancer].

PubMed

Naito, Yutaka; Yoshioka, Yusuke; Ochiya, Takahiro

2015-06-01

Intercellular communication plays an important role in the regulation of various cellular events. In particular, cancer cells and the surrounding cells communicate with each other, and this intercellular communication triggers cancer initiation and progression through the secretion of molecules, including growth factors and cytokines. Recent advances in cancer biology have indicated that small membrane vesicles, termed exosomes, also serve as regulatory agents in intercellular communications. Exosomes contain functional cellular components, including proteins and microRNAs (miRNAs), and they transfer these components to recipient cells. This exosome-mediated intercellular communication leads to increased growth, invasion, and metastasis of cancer. Thus, researchers regard exosomes as important cues to understanding the molecular mechanisms of cancer biology. Indeed, several lines of evidence have demonstrated that exosomes can explain multiple aspects of cancer biology. In addition, increasing evidence suggests that exosomes and their specific molecules are also attractive for use as biomarkers and therapeutic targets in cancer. Recent reports showed the efficacy of a novel diagnosis by detecting component molecules of cancer-derived exosomes, including miRNAs and membrane proteins. Furthermore, clinical trials that test the application of exosomes for cancer therapy have already been reported. From these points of view, we will summarize experimental data that support the role of exosomes in cancer progression and the potential of exosomes for use in novel diagnostic and therapeutic approaches for cancer.

[Anti-epidermal growth factor receptor treatment: a new paradigm for conducting therapeutic trials].

PubMed

Marty, Michel; Bedairia, Naima; Armand, Jean-Pierre

2003-11-01

Agents which modify biological properties of tumour tissue can target many tenths of functions over- or underexpressed in human tumours. In general these agents are cytostatic rather than cytotoxic and will affect only that fraction of human tumours where the target plays and important and unique role for the viability of the tumour tissue. Alternatively it is expected that acute toxicity will not be observed at active dose-time exposure; rather subacute or chronic toxicity can be observed with these agents. Clinical studies will have to follow the following rules: characterisation of the pharmacological target and of its functional role on tumour tissue; definition of an optimal biological dose rather than a maximum tolerated dose; importance of validated pharmacodynamic endpoints; importance and thus need for early studies of combination regimens. It is still too early to define general guidelines for the study of these different therapeutic families. Nevertheless, studies already conducted with agents interfering with EGF mediated signalization have already permitted preliminary indications on pharmacodynamics, target assessment, level of activity and conduct of clinical trials with combination regimens.

The Information Content of Discrete Functions and Their Application in Genetic Data Analysis

DOE PAGES

Sakhanenko, Nikita A.; Kunert-Graf, James; Galas, David J.

2017-10-13

The complex of central problems in data analysis consists of three components: (1) detecting the dependence of variables using quantitative measures, (2) defining the significance of these dependence measures, and (3) inferring the functional relationships among dependent variables. We have argued previously that an information theory approach allows separation of the detection problem from the inference of functional form problem. We approach here the third component of inferring functional forms based on information encoded in the functions. Here, we present here a direct method for classifying the functional forms of discrete functions of three variables represented in data sets. Discretemore » variables are frequently encountered in data analysis, both as the result of inherently categorical variables and from the binning of continuous numerical variables into discrete alphabets of values. The fundamental question of how much information is contained in a given function is answered for these discrete functions, and their surprisingly complex relationships are illustrated. The all-important effect of noise on the inference of function classes is found to be highly heterogeneous and reveals some unexpected patterns. We apply this classification approach to an important area of biological data analysis—that of inference of genetic interactions. Genetic analysis provides a rich source of real and complex biological data analysis problems, and our general methods provide an analytical basis and tools for characterizing genetic problems and for analyzing genetic data. Finally, we illustrate the functional description and the classes of a number of common genetic interaction modes and also show how different modes vary widely in their sensitivity to noise.« less

The Information Content of Discrete Functions and Their Application in Genetic Data Analysis

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

Sakhanenko, Nikita A.; Kunert-Graf, James; Galas, David J.

The complex of central problems in data analysis consists of three components: (1) detecting the dependence of variables using quantitative measures, (2) defining the significance of these dependence measures, and (3) inferring the functional relationships among dependent variables. We have argued previously that an information theory approach allows separation of the detection problem from the inference of functional form problem. We approach here the third component of inferring functional forms based on information encoded in the functions. Here, we present here a direct method for classifying the functional forms of discrete functions of three variables represented in data sets. Discretemore » variables are frequently encountered in data analysis, both as the result of inherently categorical variables and from the binning of continuous numerical variables into discrete alphabets of values. The fundamental question of how much information is contained in a given function is answered for these discrete functions, and their surprisingly complex relationships are illustrated. The all-important effect of noise on the inference of function classes is found to be highly heterogeneous and reveals some unexpected patterns. We apply this classification approach to an important area of biological data analysis—that of inference of genetic interactions. Genetic analysis provides a rich source of real and complex biological data analysis problems, and our general methods provide an analytical basis and tools for characterizing genetic problems and for analyzing genetic data. Finally, we illustrate the functional description and the classes of a number of common genetic interaction modes and also show how different modes vary widely in their sensitivity to noise.« less

The Information Content of Discrete Functions and Their Application in Genetic Data Analysis.

PubMed

Sakhanenko, Nikita A; Kunert-Graf, James; Galas, David J

2017-12-01

The complex of central problems in data analysis consists of three components: (1) detecting the dependence of variables using quantitative measures, (2) defining the significance of these dependence measures, and (3) inferring the functional relationships among dependent variables. We have argued previously that an information theory approach allows separation of the detection problem from the inference of functional form problem. We approach here the third component of inferring functional forms based on information encoded in the functions. We present here a direct method for classifying the functional forms of discrete functions of three variables represented in data sets. Discrete variables are frequently encountered in data analysis, both as the result of inherently categorical variables and from the binning of continuous numerical variables into discrete alphabets of values. The fundamental question of how much information is contained in a given function is answered for these discrete functions, and their surprisingly complex relationships are illustrated. The all-important effect of noise on the inference of function classes is found to be highly heterogeneous and reveals some unexpected patterns. We apply this classification approach to an important area of biological data analysis-that of inference of genetic interactions. Genetic analysis provides a rich source of real and complex biological data analysis problems, and our general methods provide an analytical basis and tools for characterizing genetic problems and for analyzing genetic data. We illustrate the functional description and the classes of a number of common genetic interaction modes and also show how different modes vary widely in their sensitivity to noise.

Maternal exposure to metals—Concentrations and predictors of exposure

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

Callan, A.C., E-mail: a.callan@ecu.edu.au; Hinwood, A.L.; Ramalingam, M.

2013-10-15

A variety of metals are important for biological function but have also been shown to impact health at elevated concentrations, whereas others have no known biological function. Pregnant women are a vulnerable population and measures to reduce exposure in this group are important. We undertook a study of maternal exposure to the metals, aluminium, arsenic, copper, cobalt, chromium, lithium, manganese, nickel, selenium, tin, uranium and zinc in 173 participants across Western Australia. Each participant provided a whole blood and urine sample, as well as drinking water, residential soil and dust samples and completed a questionnaire. In general the concentrations ofmore » metals in all samples were low with the notable exception of uranium (blood U mean 0.07 µg/L, range <0.01–0.25 µg/L; urinary U mean 0.018 µg/g creatinine, range <0.01–0.199 µg/g creatinine). Factors that influenced biological concentrations were consumption of fish which increased urinary arsenic concentrations, hobbies (including mechanics and welding) which increased blood manganese concentrations and iron/folic acid supplement use which was associated with decreased concentrations of aluminium and nickel in urine and manganese in blood. Environmental concentrations of aluminium, copper and lithium were found to influence biological concentrations, but this was not the case for other environmental metals concentrations. Further work is underway to explore the influence of diet on biological metals concentrations in more detail. The high concentrations of uranium require further investigation. -- Highlights: • High concentrations of uranium with respect to international literature. • Environmental concentrations of Al, Cu and Li influenced urinary concentrations. • Exposure to mechanics/welding hobbies increased blood Mn concentrations. • Iron/Folic acid supplements reduced biological concentrations of Al, Ni and Mn.« less

Effect of supplemental taurine on juvenile channel catfish Ictalurus punctatus growth

USDA-ARS?s Scientific Manuscript database

Taurine is a beta-amino sulfur amino acid found in most animal tissues. It has many important biological functions in mammals including membrane stabilization, antioxidation, cellular osmoregulation, detoxification, neuromodulation, and brain and eye development. Taurine supplementation in juvenil...

Mapping landscape corridors

Treesearch

Peter Vogt; Kurt H. Riitters; Marcin Iwanowski; Christine Estreguil; Jacek Kozak; Pierre Soille

2007-01-01

Corridors are important geographic features for biological conservation and biodiversity assessment. The identification and mapping of corridors is usually based on visual interpretations of movement patterns (functional corridors) or habitat maps (structural corridors). We present a method for automated corridor mapping with morphological image processing, and...

Loss of Mitochondrial Function Impairs Lysosomes.

PubMed

Demers-Lamarche, Julie; Guillebaud, Gérald; Tlili, Mouna; Todkar, Kiran; Bélanger, Noémie; Grondin, Martine; Nguyen, Angela P; Michel, Jennifer; Germain, Marc

2016-05-06

Alterations in mitochondrial function, as observed in neurodegenerative diseases, lead to disrupted energy metabolism and production of damaging reactive oxygen species. Here, we demonstrate that mitochondrial dysfunction also disrupts the structure and function of lysosomes, the main degradation and recycling organelle. Specifically, inhibition of mitochondrial function, following deletion of the mitochondrial protein AIF, OPA1, or PINK1, as well as chemical inhibition of the electron transport chain, impaired lysosomal activity and caused the appearance of large lysosomal vacuoles. Importantly, our results show that lysosomal impairment is dependent on reactive oxygen species. Given that alterations in both mitochondrial function and lysosomal activity are key features of neurodegenerative diseases, this work provides important insights into the etiology of neurodegenerative diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The expanding regulatory universe of p53 in gastrointestinal cancer.

PubMed

Fesler, Andrew; Zhang, Ning; Ju, Jingfang

2016-01-01

Tumor suppresser gene TP53 is one of the most frequently deleted or mutated genes in gastrointestinal cancers. As a transcription factor, p53 regulates a number of important protein coding genes to control cell cycle, cell death, DNA damage/repair, stemness, differentiation and other key cellular functions. In addition, p53 is also able to activate the expression of a number of small non-coding microRNAs (miRNAs) through direct binding to the promoter region of these miRNAs.  Many miRNAs have been identified to be potential tumor suppressors by regulating key effecter target mRNAs. Our understanding of the regulatory network of p53 has recently expanded to include long non-coding RNAs (lncRNAs). Like miRNA, lncRNAs have been found to play important roles in cancer biology.  With our increased understanding of the important functions of these non-coding RNAs and their relationship with p53, we are gaining exciting new insights into the biology and function of cells in response to various growth environment changes. In this review we summarize the current understanding of the ever expanding involvement of non-coding RNAs in the p53 regulatory network and its implications for our understanding of gastrointestinal cancer.

Time dependent-density functional theory (TD-DFT) and experimental studies of UV-Visible spectra and cyclic voltammetry for Cu(II) complex with Et2DTC

NASA Astrophysics Data System (ADS)

Valle, Eliana Maira A.; Maltarollo, Vinicius Gonçalves; Almeida, Michell O.; Honorio, Kathia Maria; dos Santos, Mauro Coelho; Cerchiaro, Giselle

2018-04-01

In this work, we studied the complexation mode between copper(II) ion and the specific ligand investigated as carriers of metals though biological membranes, diethyldithiocarbamate (Et2DTC). It is important to understand how this occurs because it is an important intracellular chelator with potential therapeutic applications. Theoretical and experimental UV visible studies were performed to investigate the complexation mode between copper and the ligand. Electrochemical studies were also performed to complement the spectroscopic analyses. According to the theoretical calculations, using TD-DFT (Time dependent density functional theory), with B3LYP functional and DGDVZP basis set, implemented in Gaussian 03 package, it was observed that the formation of the complex [Cu(Et2DTC)2] is favorable with higher electron density over the sulfur atoms of the ligand. UV/Vis spectra have a charge transfer band at 450 nm, with the DMSO-d6 band shift from 800 to 650 nm. The electrochemical experiments showed the formation of a new redox process, referring to the complex, where the reduction peak potential of copper is displaced to less positive region. Therefore, the results obtained from this study give important insights on possible mechanisms involved in several biological processes related to the studied system.

A new multi-scale method to reveal hierarchical modular structures in biological networks.

PubMed

Jiao, Qing-Ju; Huang, Yan; Shen, Hong-Bin

2016-11-15

Biological networks are effective tools for studying molecular interactions. Modular structure, in which genes or proteins may tend to be associated with functional modules or protein complexes, is a remarkable feature of biological networks. Mining modular structure from biological networks enables us to focus on a set of potentially important nodes, which provides a reliable guide to future biological experiments. The first fundamental challenge in mining modular structure from biological networks is that the quality of the observed network data is usually low owing to noise and incompleteness in the obtained networks. The second problem that poses a challenge to existing approaches to the mining of modular structure is that the organization of both functional modules and protein complexes in networks is far more complicated than was ever thought. For instance, the sizes of different modules vary considerably from each other and they often form multi-scale hierarchical structures. To solve these problems, we propose a new multi-scale protocol for mining modular structure (named ISIMB) driven by a node similarity metric, which works in an iteratively converged space to reduce the effects of the low data quality of the observed network data. The multi-scale node similarity metric couples both the local and the global topology of the network with a resolution regulator. By varying this resolution regulator to give different weightings to the local and global terms in the metric, the ISIMB method is able to fit the shape of modules and to detect them on different scales. Experiments on protein-protein interaction and genetic interaction networks show that our method can not only mine functional modules and protein complexes successfully, but can also predict functional modules from specific to general and reveal the hierarchical organization of protein complexes.

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

PubMed

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

2012-08-01

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

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

PubMed

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

2015-11-01

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

Click Chemistry Mediated Functionalization of Vertical Nanowires for Biological Applications.

PubMed

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

2016-01-11

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

Lone pair-π interactions in biological systems: occurrence, function, and physical origin.

PubMed

Kozelka, Jiří

2017-12-01

Lone pair-π interactions are now recognized as a supramolecular bond whose existence in biological systems is documented by a growing number of examples. They are commonly attributed to electrostatic forces. This review attempts to highlight some recent discoveries evidencing the important role which lone pair-π interactions, and anion-π interactions in particular, play in stabilizing the structure and affecting the function of biomolecules. Special attention is paid to studies exploring the physical origin of these at first glance counterintuitive interactions between a lone pair of electrons of one residue and the π-cloud of another. Recent theoretical work went beyond the popular electrostatic model and inquired the extent to which orbital interactions have to be taken into account. In at least one biologically relevant case-that of anion-flavin interactions-a substantial charge-transfer component has been shown to operate.

Biopathways representation and simulation on hybrid functional petri net.

PubMed

Matsuno, Hiroshi; Tanaka, Yukiko; Aoshima, Hitoshi; Doi, Atsushi; Matsui, Mika; Miyano, Satoru

2011-01-01

The following two matters should be resolved in order for biosimulation tools to be accepted by users in biology/medicine: (1) remove issues which are irrelevant to biological importance, and (2) allow users to represent biopathways intuitively and understand/manage easily the details of representation and simulation mechanism. From these criteria, we firstly define a novel notion of Petri net called Hybrid Functional Petri Net (HFPN). Then, we introduce a software tool, Genomic Object Net, for representing and simulating biopathways, which we have developed by employing the architecture of HFPN. In order to show the usefulness of Genomic Object Net for representing and simulating biopathways, we show two HFPN representations of gene regulation mechanisms of Drosophila melanogaster (fruit fly) circadian rhythm and apoptosis induced by Fas ligand. The simulation results of these biopathways are also correlated with biological observations. The software is available to academic users from http://www.GenomicObject.Net/.

Fluorogenic RNA Mango aptamers for imaging small non-coding RNAs in mammalian cells.

PubMed

Autour, Alexis; C Y Jeng, Sunny; D Cawte, Adam; Abdolahzadeh, Amir; Galli, Angela; Panchapakesan, Shanker S S; Rueda, David; Ryckelynck, Michael; Unrau, Peter J

2018-02-13

Despite having many key roles in cellular biology, directly imaging biologically important RNAs has been hindered by a lack of fluorescent tools equivalent to the fluorescent proteins available to study cellular proteins. Ideal RNA labelling systems must preserve biological function, have photophysical properties similar to existing fluorescent proteins, and be compatible with established live and fixed cell protein labelling strategies. Here, we report a microfluidics-based selection of three new high-affinity RNA Mango fluorogenic aptamers. Two of these are as bright or brighter than enhanced GFP when bound to TO1-Biotin. Furthermore, we show that the new Mangos can accurately image the subcellular localization of three small non-coding RNAs (5S, U6, and a box C/D scaRNA) in fixed and live mammalian cells. These new aptamers have many potential applications to study RNA function and dynamics both in vitro and in mammalian cells.

Serine Proteases of Parasitic Helminths

PubMed Central

Yang, Yong; Wen, Yun jun; Cai, Ya Nan; Vallée, Isabelle; Boireau, Pascal; Liu, Ming Yuan; Cheng, Shi Peng

2015-01-01

Serine proteases form one of the most important families of enzymes and perform significant functions in a broad range of biological processes, such as intra- and extracellular protein metabolism, digestion, blood coagulation, regulation of development, and fertilization. A number of serine proteases have been identified in parasitic helminths that have putative roles in parasite development and nutrition, host tissues and cell invasion, anticoagulation, and immune evasion. In this review, we described the serine proteases that have been identified in parasitic helminths, including nematodes (Trichinella spiralis, T. pseudospiralis, Trichuris muris, Anisakis simplex, Ascaris suum, Onchocerca volvulus, O. lienalis, Brugia malayi, Ancylostoma caninum, and Steinernema carpocapsae), cestodes (Spirometra mansoni, Echinococcus granulosus, and Schistocephalus solidus), and trematodes (Fasciola hepatica, F. gigantica, and Schistosoma mansoni). Moreover, the possible biological functions of these serine proteases in the endogenous biological phenomena of these parasites and in the host-parasite interaction were also discussed. PMID:25748703

Gap assessment in current soil monitoring networks across Europe for measuring soil functions

NASA Astrophysics Data System (ADS)

van Leeuwen, J. P.; Saby, N. P. A.; Jones, A.; Louwagie, G.; Micheli, E.; Rutgers, M.; Schulte, R. P. O.; Spiegel, H.; Toth, G.; Creamer, R. E.

2017-12-01

Soil is the most important natural resource for life on Earth after water. Given its fundamental role in sustaining the human population, both the availability and quality of soil must be managed sustainably and protected. To ensure sustainable management we need to understand the intrinsic functional capacity of different soils across Europe and how it changes over time. Soil monitoring is needed to support evidence-based policies to incentivise sustainable soil management. To this aim, we assessed which soil attributes can be used as potential indicators of five soil functions; (1) primary production, (2) water purification and regulation, (3) carbon sequestration and climate regulation, (4) soil biodiversity and habitat provisioning and (5) recycling of nutrients. We compared this list of attributes to existing national (regional) and EU-wide soil monitoring networks. The overall picture highlighted a clearly unbalanced dataset, in which predominantly chemical soil parameters were included, and soil biological and physical attributes were severely under represented. Methods applied across countries for indicators also varied. At a European scale, the LUCAS-soil survey was evaluated and again confirmed a lack of important soil biological parameters, such as C mineralisation rate, microbial biomass and earthworm community, and soil physical measures such as bulk density. In summary, no current national or European monitoring system exists which has the capacity to quantify the five soil functions and therefore evaluate multi-functional capacity of a soil and in many countries no data exists at all. This paper calls for the addition of soil biological and some physical parameters within the LUCAS-soil survey at European scale and for further development of national soil monitoring schemes.

Chorusing, synchrony, and the evolutionary functions of rhythm.

PubMed

Ravignani, Andrea; Bowling, Daniel L; Fitch, W Tecumseh

2014-01-01

A central goal of biomusicology is to understand the biological basis of human musicality. One approach to this problem has been to compare core components of human musicality (relative pitch perception, entrainment, etc.) with similar capacities in other animal species. Here we extend and clarify this comparative approach with respect to rhythm. First, whereas most comparisons between human music and animal acoustic behavior have focused on spectral properties (melody and harmony), we argue for the central importance of temporal properties, and propose that this domain is ripe for further comparative research. Second, whereas most rhythm research in non-human animals has examined animal timing in isolation, we consider how chorusing dynamics can shape individual timing, as in human music and dance, arguing that group behavior is key to understanding the adaptive functions of rhythm. To illustrate the interdependence between individual and chorusing dynamics, we present a computational model of chorusing agents relating individual call timing with synchronous group behavior. Third, we distinguish and clarify mechanistic and functional explanations of rhythmic phenomena, often conflated in the literature, arguing that this distinction is key for understanding the evolution of musicality. Fourth, we expand biomusicological discussions beyond the species typically considered, providing an overview of chorusing and rhythmic behavior across a broad range of taxa (orthopterans, fireflies, frogs, birds, and primates). Finally, we propose an "Evolving Signal Timing" hypothesis, suggesting that similarities between timing abilities in biological species will be based on comparable chorusing behaviors. We conclude that the comparative study of chorusing species can provide important insights into the adaptive function(s) of rhythmic behavior in our "proto-musical" primate ancestors, and thus inform our understanding of the biology and evolution of rhythm in human music and language.

Chorusing, synchrony, and the evolutionary functions of rhythm

PubMed Central

Ravignani, Andrea; Bowling, Daniel L.; Fitch, W. Tecumseh

2014-01-01

A central goal of biomusicology is to understand the biological basis of human musicality. One approach to this problem has been to compare core components of human musicality (relative pitch perception, entrainment, etc.) with similar capacities in other animal species. Here we extend and clarify this comparative approach with respect to rhythm. First, whereas most comparisons between human music and animal acoustic behavior have focused on spectral properties (melody and harmony), we argue for the central importance of temporal properties, and propose that this domain is ripe for further comparative research. Second, whereas most rhythm research in non-human animals has examined animal timing in isolation, we consider how chorusing dynamics can shape individual timing, as in human music and dance, arguing that group behavior is key to understanding the adaptive functions of rhythm. To illustrate the interdependence between individual and chorusing dynamics, we present a computational model of chorusing agents relating individual call timing with synchronous group behavior. Third, we distinguish and clarify mechanistic and functional explanations of rhythmic phenomena, often conflated in the literature, arguing that this distinction is key for understanding the evolution of musicality. Fourth, we expand biomusicological discussions beyond the species typically considered, providing an overview of chorusing and rhythmic behavior across a broad range of taxa (orthopterans, fireflies, frogs, birds, and primates). Finally, we propose an “Evolving Signal Timing” hypothesis, suggesting that similarities between timing abilities in biological species will be based on comparable chorusing behaviors. We conclude that the comparative study of chorusing species can provide important insights into the adaptive function(s) of rhythmic behavior in our “proto-musical” primate ancestors, and thus inform our understanding of the biology and evolution of rhythm in human music and language. PMID:25346705

C-terminal domains of bacterial proteases: structure, function and the biotechnological applications.

PubMed

Huang, J; Wu, C; Liu, D; Yang, X; Wu, R; Zhang, J; Ma, C; He, H

2017-01-01

C-terminal domains widely exist in the C-terminal region of multidomain proteases. As a β-sandwich domain in multidomain protease, the C-terminal domain plays an important role in proteolysis including regulation of the secretory process, anchoring and swelling the substrate molecule, presenting as an inhibitor for the preprotease and adapting the protein structural flexibility and stability. In this review, the diversity, structural characteristics and biological function of C-terminal protease domains are described. Furthermore, the application prospects of C-terminal domains, including polycystic kidney disease, prepeptidase C-terminal and collagen-binding domain, in the area of medicine and biological artificial materials are also discussed. © 2016 The Society for Applied Microbiology.

A Framework to Quantify the Strength of the Ecological Links ...

EPA Pesticide Factsheets

Anthropogenic stressors such as climate change, fire, and pollution are driving shifts in ecosystem function and resilience. Scientists generally rely on biological indicators of these stressors to signal that ecosystem conditions have been altered beyond an acceptable amount. However, these biological indicators are not always capable of being directly related to ecosystem services that allow scientists to communicate the importance of the change to land managers and policy makers. Therefore, we developed the STEPS (STressor – Ecological Production function – final ecosystem goods and Services) Framework to link changes in a biological indicator of a stressor to Final Ecosystem Goods and Services (FEGS). The STEPS framework produces “chains” of ecological components that connect the change in a biological indicator to the Final Ecosystem Goods and Services Classification System (FEGS-CS). The series of ecological components is an ecological production functions (EPF) which links a biological indicator of a stressor to an ecological endpoint (i.e., FEGS) that is directly used, appreciated, or valued by humans. The framework uses a qualitative score (High, Medium, Low) for the Strength of Science (SOS) for the relationship between each of the components in the EPF to identify research gaps and prioritize decision making based on what research has been completed. The ecological endpoint of the EPF is a FEGS to which discrete Beneficiaries, or direct users

The Wolffian roots of Kant's teleology.

PubMed

van den Berg, Hein

2013-12-01

Kant's teleology as presented in the Critique of Judgment is commonly interpreted in relation to the late eighteenth-century biological research of Johann Friedrich Blumenbach. In the present paper, I show that this interpretative perspective is incomplete. Understanding Kant's views on teleology and biology requires a consideration of the teleological and biological views of Christian Wolff and his rationalist successors. By reconstructing the Wolffian roots of Kant's teleology, I identify several little known sources of Kant's views on biology. I argue that one of Kant's main contributions to eighteenth-century debates on biology consisted in demarcating biology from metaphysics. Kant rejected Wolffian views on the hierarchy of sciences, according to which propositions specifying the functions of organisms are derived from theological truths. In addition, Kant argued that organic self-organization necessitates a teleological description in order to show that self-organization does not support materialism. By demarcating biology and metaphysics, Kant made a small yet important contribution to establishing biology as a science. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evolution viewed from physics, physiology and medicine.

PubMed

Noble, Denis

2017-10-06

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

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

PubMed

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.

From Commodity Polymers to Functional Polymers

PubMed Central

Xiang, Tao; Wang, Ling-Ren; Ma, Lang; Han, Zhi-Yuan; Wang, Rui; Cheng, Chong; Xia, Yi; Qin, Hui; Zhao, Chang-Sheng

2014-01-01

Functional polymers bear specified chemical groups, and have specified physical, chemical, biological, pharmacological, or other uses. To adjust the properties while keeping material usage low, a method for direct synthesis of functional polymers is indispensable. Here we show that various functional polymers can be synthesized by in situ cross-linked polymerization/copolymerization. We demonstrate that the polymers synthesized by the facile method using different functional monomers own outstanding pH-sensitivity and pH-reversibility, antifouling property, antibacterial, and anticoagulant property. Our study opens a route for the functionalization of commodity polymers, which lead to important advances in polymeric materials applications. PMID:24710333

Antioxidative properties of functional polyphenols and their metabolites assessed by an ORAC assay.

PubMed

Ishimoto, Hidekazu; Tai, Akihiro; Yoshimura, Morio; Amakura, Yoshiaki; Yoshida, Takashi; Hatano, Tsutomu; Ito, Hideyuki

2012-01-01

We compared the antioxidative activities of polyphenol metabolites with those of intact functional polyphenols by an assay of the oxygen radical absorbance capacity (ORAC). The metabolites of ellagitannin geraniin, chlorogenic acid, and (-)-epigallocatechin gallate displayed more potent antioxidative activity than their respective original compounds. Our findings suggest that these metabolites may play important roles as biological antioxidants after their consumption.

Bioinspiration: applying mechanical design to experimental biology.

PubMed

Flammang, Brooke E; Porter, Marianne E

2011-07-01

The production of bioinspired and biomimetic constructs has fostered much collaboration between biologists and engineers, although the extent of biological accuracy employed in the designs produced has not always been a priority. Even the exact definitions of "bioinspired" and "biomimetic" differ among biologists, engineers, and industrial designers, leading to confusion regarding the level of integration and replication of biological principles and physiology. By any name, biologically-inspired mechanical constructs have become an increasingly important research tool in experimental biology, offering the opportunity to focus research by creating model organisms that can be easily manipulated to fill a desired parameter space of structural and functional repertoires. Innovative researchers with both biological and engineering backgrounds have found ways to use bioinspired models to explore the biomechanics of organisms from all kingdoms to answer a variety of different questions. Bringing together these biologists and engineers will hopefully result in an open discourse of techniques and fruitful collaborations for experimental and industrial endeavors.

A Proteogenomic Approach to Understanding MYC Function in Metastatic Medulloblastoma Tumors.

PubMed

Staal, Jerome A; Pei, Yanxin; Rood, Brian R

2016-10-19

Brain tumors are the leading cause of cancer-related deaths in children, and medulloblastoma is the most prevalent malignant childhood/pediatric brain tumor. Providing effective treatment for these cancers, with minimal damage to the still-developing brain, remains one of the greatest challenges faced by clinicians. Understanding the diverse events driving tumor formation, maintenance, progression, and recurrence is necessary for identifying novel targeted therapeutics and improving survival of patients with this disease. Genomic copy number alteration data, together with clinical studies, identifies c-MYC amplification as an important risk factor associated with the most aggressive forms of medulloblastoma with marked metastatic potential. Yet despite this, very little is known regarding the impact of such genomic abnormalities upon the functional biology of the tumor cell. We discuss here how recent advances in quantitative proteomic techniques are now providing new insights into the functional biology of these aggressive tumors, as illustrated by the use of proteomics to bridge the gap between the genotype and phenotype in the case of c-MYC -amplified/associated medulloblastoma. These integrated proteogenomic approaches now provide a new platform for understanding cancer biology by providing a functional context to frame genomic abnormalities.

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

PubMed

Simmen, Thomas; Tagaya, Mitsuo

2017-01-01

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

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

PubMed

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

2015-12-01

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

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

PubMed

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

2014-02-01

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

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

PubMed Central

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

2014-01-01

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

Functional anthology of intrinsic disorder. 3. Ligands, post-translational modifications, and diseases associated with intrinsically disordered proteins.

PubMed

Xie, Hongbo; Vucetic, Slobodan; Iakoucheva, Lilia M; Oldfield, Christopher J; Dunker, A Keith; Obradovic, Zoran; Uversky, Vladimir N

2007-05-01

Currently, the understanding of the relationships between function, amino acid sequence, and protein structure continues to represent one of the major challenges of the modern protein science. As many as 50% of eukaryotic proteins are likely to contain functionally important long disordered regions. Many proteins are wholly disordered but still possess numerous biologically important functions. However, the number of experimentally confirmed disordered proteins with known biological functions is substantially smaller than their actual number in nature. Therefore, there is a crucial need for novel bionformatics approaches that allow projection of the current knowledge from a few experimentally verified examples to much larger groups of known and potential proteins. The elaboration of a bioinformatics tool for the analysis of functional diversity of intrinsically disordered proteins and application of this data mining tool to >200 000 proteins from the Swiss-Prot database, each annotated with at least one of the 875 functional keywords, was described in the first paper of this series (Xie, H.; Vucetic, S.; Iakoucheva, L. M.; Oldfield, C. J.; Dunker, A. K.; Obradovic, Z.; Uversky, V.N. Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions. J. Proteome Res. 2007, 5, 1882-1898). Using this tool, we have found that out of the 710 Swiss-Prot functional keywords associated with at least 20 proteins, 262 were strongly positively correlated with long intrinsically disordered regions, and 302 were strongly negatively correlated. Illustrative examples of functional disorder or order were found for the vast majority of keywords showing strongest positive or negative correlation with intrinsic disorder, respectively. Some 80 Swiss-Prot keywords associated with disorder- and order-driven biological processes and protein functions were described in the first paper (see above). The second paper of the series was devoted to the presentation of 87 Swiss-Prot keywords attributed to the cellular components, domains, technical terms, developmental processes, and coding sequence diversities possessing strong positive and negative correlation with long disordered regions (Vucetic, S.; Xie, H.; Iakoucheva, L. M.; Oldfield, C. J.; Dunker, A. K.; Obradovic, Z.; Uversky, V. N. Functional anthology of intrinsic disorder. 2. Cellular components, domains, technical terms, developmental processes, and coding sequence diversities correlated with long disordered regions. J. Proteome Res. 2007, 5, 1899-1916). Protein structure and functionality can be modulated by various post-translational modifications or/and as a result of binding of specific ligands. Numerous human diseases are associated with protein misfolding/misassembly/misfunctioning. This work concludes the series of papers dedicated to the functional anthology of intrinsic disorder and describes approximately 80 Swiss-Prot functional keywords that are related to ligands, post-translational modifications, and diseases possessing strong positive or negative correlation with the predicted long disordered regions in proteins.

The Biology of Neisseria Adhesins

PubMed Central

Hung, Miao-Chiu; Christodoulides, Myron

2013-01-01

Members of the genus Neisseria include pathogens causing important human diseases such as meningitis, septicaemia, gonorrhoea and pelvic inflammatory disease syndrome. Neisseriae are found on the exposed epithelia of the upper respiratory tract and the urogenital tract. Colonisation of these exposed epithelia is dependent on a repertoire of diverse bacterial molecules, extending not only from the surface of the bacteria but also found within the outer membrane. During invasive disease, pathogenic Neisseriae also interact with immune effector cells, vascular endothelia and the meninges. Neisseria adhesion involves the interplay of these multiple surface factors and in this review we discuss the structure and function of these important molecules and the nature of the host cell receptors and mechanisms involved in their recognition. We also describe the current status for recently identified Neisseria adhesins. Understanding the biology of Neisseria adhesins has an impact not only on the development of new vaccines but also in revealing fundamental knowledge about human biology. PMID:24833056

Androgens: basic biology and clinical implication.

PubMed

Orwoll, E S

2001-10-01

Although androgens have been considered essential modulators of bone biology in men, recent studies have indicated that estrogen may have an important, if not dominant, role. Nevertheless, there is strong evidence that androgens have independent skeletal actions. Nonaromatizable androgens influence a variety of aspects of bone cell biology and are capable of modulating bone remodeling and bone mass. It appears that androgens are particularly important in the control of periosteal bone formation, an effect that might underlie the gender difference in bone size. Alterations in androgen receptor function affect bone metabolism, and new information suggests that androgens modulate receptor homeostasis. The clinical implications of androgen effects, and how they interact with those of estrogens, are somewhat unclear. It is likely that overall bone homeostasis and gender differences depend on a combination of androgenic and estrogenic actions. Androgens may well provide advantages in the prevention and therapy of metabolic bone disorders in both men and women.

NO, nitrosonium ions, nitroxide ions, nitrosothiols and iron-nitrosyls in biology: a chemist's perspective.

PubMed

Butler, A R; Flitney, F W; Williams, D L

1995-01-01

The multiplicity of biological functions thus far attributed to NO has led to suggestions that some effects might be mediated by other, related species instead. The radical nature of NO cannot account for its cytotoxicity, but its reaction with superoxide to form peroxynitite and highly reactive hydroxyl radicals may be important in this context. The ease with which NO can react with and destroy Fe-S clusters is also an important factor. Nitrosonium and nitroxide ions can be produced in vivo and will react under conditions that are physiologically relevant. Both could, in theory, serve in cell signalling or as cytotoxic agents. More direct experimental evidence for their involvement is needed before we can confidently assign them specific biological roles. In this article, Anthony Butler, Frederick Flitney and Lyn Williams discuss the chemistry of NO and related species.

Computational modeling of diffusion in the cerebellum.

PubMed

Marinov, Toma M; Santamaria, Fidel

2014-01-01

Diffusion is a major transport mechanism in living organisms. In the cerebellum, diffusion is responsible for the propagation of molecular signaling involved in synaptic plasticity and metabolism, both intracellularly and extracellularly. In this chapter, we present an overview of the cerebellar structure and function. We then discuss the types of diffusion processes present in the cerebellum and their biological importance. We particularly emphasize the differences between extracellular and intracellular diffusion and the presence of tortuosity and anomalous diffusion in different parts of the cerebellar cortex. We provide a mathematical introduction to diffusion and a conceptual overview of various computational modeling techniques. We discuss their scope and their limit of application. Although our focus is the cerebellum, we have aimed at presenting the biological and mathematical foundations as general as possible to be applicable to any other area in biology in which diffusion is of importance. © 2014 Elsevier Inc. All rights reserved.

The Importance of Normalization on Large and Heterogeneous Microarray Datasets

EPA Science Inventory

DNA microarray technology is a powerful functional genomics tool increasingly used for investigating global gene expression in environmental studies. Microarrays can also be used in identifying biological networks, as they give insight on the complex gene-to-gene interactions, ne...

BIOLOGICAL INDICATOR DEVELOPMENT AND CLASSIFICATION FOR GREAT LAKES COASTAL WETLANDS

EPA Science Inventory

Great Lakes coastal wetlands are a valued aquatic resource that provide important ecological functions for the Great Lakes including serving as fish habitat, aquatic food web support, and nutrient and sediment retention from watersheds. Great Lakes resource managers need assessme...

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

EPA Science Inventory

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

Genetic insights into the mechanisms of Fgf signaling

PubMed Central

Brewer, J. Richard; Mazot, Pierre; Soriano, Philippe

2016-01-01

The fibroblast growth factor (Fgf) family of ligands and receptor tyrosine kinases is required throughout embryonic and postnatal development and also regulates multiple homeostatic functions in the adult. Aberrant Fgf signaling causes many congenital disorders and underlies multiple forms of cancer. Understanding the mechanisms that govern Fgf signaling is therefore important to appreciate many aspects of Fgf biology and disease. Here we review the mechanisms of Fgf signaling by focusing on genetic strategies that enable in vivo analysis. These studies support an important role for Erk1/2 as a mediator of Fgf signaling in many biological processes but have also provided strong evidence for additional signaling pathways in transmitting Fgf signaling in vivo. PMID:27036966

An ensemble framework for clustering protein-protein interaction networks.

PubMed

Asur, Sitaram; Ucar, Duygu; Parthasarathy, Srinivasan

2007-07-01

Protein-Protein Interaction (PPI) networks are believed to be important sources of information related to biological processes and complex metabolic functions of the cell. The presence of biologically relevant functional modules in these networks has been theorized by many researchers. However, the application of traditional clustering algorithms for extracting these modules has not been successful, largely due to the presence of noisy false positive interactions as well as specific topological challenges in the network. In this article, we propose an ensemble clustering framework to address this problem. For base clustering, we introduce two topology-based distance metrics to counteract the effects of noise. We develop a PCA-based consensus clustering technique, designed to reduce the dimensionality of the consensus problem and yield informative clusters. We also develop a soft consensus clustering variant to assign multifaceted proteins to multiple functional groups. We conduct an empirical evaluation of different consensus techniques using topology-based, information theoretic and domain-specific validation metrics and show that our approaches can provide significant benefits over other state-of-the-art approaches. Our analysis of the consensus clusters obtained demonstrates that ensemble clustering can (a) produce improved biologically significant functional groupings; and (b) facilitate soft clustering by discovering multiple functional associations for proteins. Supplementary data are available at Bioinformatics online.

PTEN: Multiple Functions in Human Malignant Tumors.

PubMed

Milella, Michele; Falcone, Italia; Conciatori, Fabiana; Cesta Incani, Ursula; Del Curatolo, Anais; Inzerilli, Nicola; Nuzzo, Carmen M A; Vaccaro, Vanja; Vari, Sabrina; Cognetti, Francesco; Ciuffreda, Ludovica

2015-01-01

PTEN is the most important negative regulator of the PI3K signaling pathway. In addition to its canonical, PI3K inhibition-dependent functions, PTEN can also function as a tumor suppressor in a PI3K-independent manner. Indeed, the PTEN network regulates a broad spectrum of biological functions, modulating the flow of information from membrane-bound growth factor receptors to nuclear transcription factors, occurring in concert with other tumor suppressors and oncogenic signaling pathways. PTEN acts through its lipid and protein phosphatase activity and other non-enzymatic mechanisms. Studies conducted over the past 10 years have expanded our understanding of the biological role of PTEN, showing that in addition to its ability to regulate proliferation and cell survival, it also plays an intriguing role in regulating genomic stability, cell migration, stem cell self-renewal, and tumor microenvironment. Changes in PTEN protein levels, location, and enzymatic activity through various molecular mechanisms can generate a continuum of functional PTEN levels in inherited syndromes, sporadic cancers, and other diseases. PTEN activity can indeed, be modulated by mutations, epigenetic silencing, transcriptional repression, aberrant protein localization, and post-translational modifications. This review will discuss our current understanding of the biological role of PTEN, how PTEN expression and activity are regulated, and the consequences of PTEN dysregulation in human malignant tumors.

PTEN: Multiple Functions in Human Malignant Tumors

PubMed Central

Milella, Michele; Falcone, Italia; Conciatori, Fabiana; Cesta Incani, Ursula; Del Curatolo, Anais; Inzerilli, Nicola; Nuzzo, Carmen M. A.; Vaccaro, Vanja; Vari, Sabrina; Cognetti, Francesco; Ciuffreda, Ludovica

2015-01-01

PTEN is the most important negative regulator of the PI3K signaling pathway. In addition to its canonical, PI3K inhibition-dependent functions, PTEN can also function as a tumor suppressor in a PI3K-independent manner. Indeed, the PTEN network regulates a broad spectrum of biological functions, modulating the flow of information from membrane-bound growth factor receptors to nuclear transcription factors, occurring in concert with other tumor suppressors and oncogenic signaling pathways. PTEN acts through its lipid and protein phosphatase activity and other non-enzymatic mechanisms. Studies conducted over the past 10 years have expanded our understanding of the biological role of PTEN, showing that in addition to its ability to regulate proliferation and cell survival, it also plays an intriguing role in regulating genomic stability, cell migration, stem cell self-renewal, and tumor microenvironment. Changes in PTEN protein levels, location, and enzymatic activity through various molecular mechanisms can generate a continuum of functional PTEN levels in inherited syndromes, sporadic cancers, and other diseases. PTEN activity can indeed, be modulated by mutations, epigenetic silencing, transcriptional repression, aberrant protein localization, and post-translational modifications. This review will discuss our current understanding of the biological role of PTEN, how PTEN expression and activity are regulated, and the consequences of PTEN dysregulation in human malignant tumors. PMID:25763354

UltraPse: A Universal and Extensible Software Platform for Representing Biological Sequences.

PubMed

Du, Pu-Feng; Zhao, Wei; Miao, Yang-Yang; Wei, Le-Yi; Wang, Likun

2017-11-14

With the avalanche of biological sequences in public databases, one of the most challenging problems in computational biology is to predict their biological functions and cellular attributes. Most of the existing prediction algorithms can only handle fixed-length numerical vectors. Therefore, it is important to be able to represent biological sequences with various lengths using fixed-length numerical vectors. Although several algorithms, as well as software implementations, have been developed to address this problem, these existing programs can only provide a fixed number of representation modes. Every time a new sequence representation mode is developed, a new program will be needed. In this paper, we propose the UltraPse as a universal software platform for this problem. The function of the UltraPse is not only to generate various existing sequence representation modes, but also to simplify all future programming works in developing novel representation modes. The extensibility of UltraPse is particularly enhanced. It allows the users to define their own representation mode, their own physicochemical properties, or even their own types of biological sequences. Moreover, UltraPse is also the fastest software of its kind. The source code package, as well as the executables for both Linux and Windows platforms, can be downloaded from the GitHub repository.

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

PubMed

Mazzola, Mark

2004-01-01

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

Biological and psychological rhythms: an integrative approach to rhythm disturbances in autistic disorder.

PubMed

Botbol, Michel; Cabon, Philippe; Kermarrec, Solenn; Tordjman, Sylvie

2013-09-01

Biological rhythms are crucial phenomena that are perfect examples of the adaptation of organisms to their environment. A considerable amount of work has described different types of biological rhythms (from circadian to ultradian), individual differences in their patterns and the complexity of their regulation. In particular, the regulation and maturation of the sleep-wake cycle have been thoroughly studied. Its desynchronization, both endogenous and exogenous, is now well understood, as are its consequences for cognitive impairments and health problems. From a completely different perspective, psychoanalysts have shown a growing interest in the rhythms of psychic life. This interest extends beyond the original focus of psychoanalysis on dreams and the sleep-wake cycle, incorporating central theoretical and practical psychoanalytic issues related to the core functioning of the psychic life: the rhythmic structures of drive dynamics, intersubjective developmental processes and psychic containment functions. Psychopathological and biological approaches to the study of infantile autism reveal the importance of specific biological and psychological rhythmic disturbances in this disorder. Considering data and hypotheses from both perspectives, this paper proposes an integrative approach to the study of these rhythmic disturbances and offers an etiopathogenic hypothesis based on this integrative approach. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reduced Gas Cycling in Microbial Mats: Implications for Early Earth

NASA Technical Reports Server (NTRS)

Hoehler, Tori M.; Bebout, Brad M.; DesMarais, David J.; DeVincenzi, Donald L. (Technical Monitor)

2000-01-01

For more than half the history of life on Earth, biological productivity was dominated by photosynthetic microbial mats. During this time, mats served as the preeminent biological influence on earth's surface and atmospheric chemistry and also as the primary crucible for microbial evolution. We find that modern analogs of these ancient mat communities generate substantial quantities of hydrogen, carbon monoxide, and methane. Escape of these gases from the biosphere would contribute strongly to atmospheric evolution and potentially to the net oxidation of earth's surface; sequestration within the biosphere carries equally important implications for the structure, function, and evolution of anaerobic microbial communities within the context of mat biology.

Synthetic biology approaches to engineer T cells.

PubMed

Wu, Chia-Yung; Rupp, Levi J; Roybal, Kole T; Lim, Wendell A

2015-08-01

There is rapidly growing interest in learning how to engineer immune cells, such as T lymphocytes, because of the potential of these engineered cells to be used for therapeutic applications such as the recognition and killing of cancer cells. At the same time, our knowhow and capability to logically engineer cellular behavior is growing rapidly with the development of synthetic biology. Here we describe how synthetic biology approaches are being used to rationally alter the behavior of T cells to optimize them for therapeutic functions. We also describe future developments that will be important in order to construct safe and precise T cell therapeutics. Copyright © 2015 Elsevier Ltd. All rights reserved.

International Journal of Quantum Chemistry, Quantum Biology Symposium No. 24. Proceedings of the International Symposium on the Application of Fundamental Theory to Problems of Biology and Pharmacology, Held at Ponce de Leon Resort, St. Augustine, Florida on March 1-7, 1997. Volume 65, No. 6, 1997.

DTIC Science & Technology

1997-03-01

characteristic musk odor [7]. Molecular shape is important in circular dichroism and chirality. Enantiomers, if viewed in isolation, have identical all...simply a function of the length of the elon - gated structure). We can introduce V/S as an index of molecular shape by using computed molecular

Copper-Catalyzed Synthesis of Trifluoroethylarenes from Benzylic Bromodifluoroacetates.

PubMed

Ambler, Brett R; Zhu, Lingui; Altman, Ryan A

2015-08-21

Trifluoroethylarenes are found in a variety of biologically active molecules, and strategies for accessing this substructure are important for developing therapeutic candidates and biological probes. Trifluoroethylarenes can be directly accessed via nucleophilic trifluoromethylation of benzylic electrophiles; however, current catalytic methods do not effectively transform electron-deficient substrates and heterocycles. To address this gap, we report a Cu-catalyzed decarboxylative trifluoromethylation of benzylic bromodifluoroacetates. To account for the tolerance of sensitive functional groups, we propose an inner-sphere mechanism of decarboxylation.

Characterization of dynamic physiology of the bladder by optical coherence tomography

NASA Astrophysics Data System (ADS)

Yuan, Zhijia; Keng, Kerri; Pan, Rubin; Ren, Hugang; Du, Congwu; Kim, Jason; Pan, Yingtian

2012-03-01

Because of its high spatial resolution and noninvasive imaging capabilities, optical coherence tomography has been used to characterize the morphological details of various biological tissues including urinary bladder and to diagnose their alternations (e.g., cancers). In addition to static morphology, the dynamic features of tissue morphology can provide important information that can be used to diagnose the physiological and functional characteristics of biological tissues. Here, we present the imaging studies based on optical coherence tomography to characterize motion related physiology and functions of rat bladder detrusor muscles and compared the results with traditional biomechanical measurements. Our results suggest that optical coherence tomography is capable of providing quantitative evaluation of contractile functions of intact bladder (without removing bladder epithelium and connective tissue), which is potentially of more clinical relevance for future clinical diagnosis - if incorporated with cystoscopic optical coherence tomography.

Long noncoding RNAs in gastric cancer: functions and clinical applications

PubMed Central

Wang, Jiajun; Sun, Jingxu; Wang, Jun; Song, Yongxi; Gao, Peng; Shi, Jinxin; Chen, Ping; Wang, Zhenning

2016-01-01

Over the last two decades, genome-wide studies have revealed that only a small fraction of the human genome encodes proteins; long noncoding RNAs (lncRNAs) account for 98% of the total genome. These RNA molecules, which are >200 nt in length, play important roles in diverse biological processes, including the immune response, stem cell pluripotency, cell proliferation, apoptosis, differentiation, invasion, and metastasis by regulating gene expression at the epigenetic, transcriptional, and posttranscriptional levels. However, the detailed molecular mechanisms underlying lncRNA function are only partially understood. Recent studies showed that many lncRNAs are aberrantly expressed in gastric cancer (GC) tissues, gastric juice, plasma, and cells, and these alterations are linked to the occurrence, progression, and outcome of GC. Here, we review the current knowledge of the biological functions and clinical aspects of lncRNAs in GC. PMID:26929639

Functional impact of splice isoform diversity in individual cells

PubMed Central

Yap, Karen; Makeyev, Eugene V.

2016-01-01

Alternative pre-mRNA splicing provides an effective means for expanding coding capacity of eukaryotic genomes. Recent studies suggest that co-expression of different splice isoforms may increase diversity of RNAs and proteins at a single-cell level. A pertinent question in the field is whether such co-expression is biologically meaningful or, rather, represents insufficiently stringent splicing regulation. Here we argue that isoform co-expression may produce functional outcomes that are difficult and sometimes impossible to achieve using other regulation strategies. Far from being a ‘splicing noise’, co-expression is often established through co-ordinated activity of specific cis-elements and trans-acting factors. Further work in this area may uncover new biological functions of alternative splicing (AS) and generate important insights into mechanisms allowing different cell types to attain their unique molecular identities. PMID:27528755

Functional impact of splice isoform diversity in individual cells.

PubMed

Yap, Karen; Makeyev, Eugene V

2016-08-15

Alternative pre-mRNA splicing provides an effective means for expanding coding capacity of eukaryotic genomes. Recent studies suggest that co-expression of different splice isoforms may increase diversity of RNAs and proteins at a single-cell level. A pertinent question in the field is whether such co-expression is biologically meaningful or, rather, represents insufficiently stringent splicing regulation. Here we argue that isoform co-expression may produce functional outcomes that are difficult and sometimes impossible to achieve using other regulation strategies. Far from being a 'splicing noise', co-expression is often established through co-ordinated activity of specific cis-elements and trans-acting factors. Further work in this area may uncover new biological functions of alternative splicing (AS) and generate important insights into mechanisms allowing different cell types to attain their unique molecular identities. © 2016 The Author(s).

Identification of Boolean Network Models From Time Series Data Incorporating Prior Knowledge.

PubMed

Leifeld, Thomas; Zhang, Zhihua; Zhang, Ping

2018-01-01

Motivation: Mathematical models take an important place in science and engineering. A model can help scientists to explain dynamic behavior of a system and to understand the functionality of system components. Since length of a time series and number of replicates is limited by the cost of experiments, Boolean networks as a structurally simple and parameter-free logical model for gene regulatory networks have attracted interests of many scientists. In order to fit into the biological contexts and to lower the data requirements, biological prior knowledge is taken into consideration during the inference procedure. In the literature, the existing identification approaches can only deal with a subset of possible types of prior knowledge. Results: We propose a new approach to identify Boolean networks from time series data incorporating prior knowledge, such as partial network structure, canalizing property, positive and negative unateness. Using vector form of Boolean variables and applying a generalized matrix multiplication called the semi-tensor product (STP), each Boolean function can be equivalently converted into a matrix expression. Based on this, the identification problem is reformulated as an integer linear programming problem to reveal the system matrix of Boolean model in a computationally efficient way, whose dynamics are consistent with the important dynamics captured in the data. By using prior knowledge the number of candidate functions can be reduced during the inference. Hence, identification incorporating prior knowledge is especially suitable for the case of small size time series data and data without sufficient stimuli. The proposed approach is illustrated with the help of a biological model of the network of oxidative stress response. Conclusions: The combination of efficient reformulation of the identification problem with the possibility to incorporate various types of prior knowledge enables the application of computational model inference to systems with limited amount of time series data. The general applicability of this methodological approach makes it suitable for a variety of biological systems and of general interest for biological and medical research.

Genomes, Proteomes and the Central Dogma

PubMed Central

Franklin, Sarah; Vondriska, Thomas M.

2011-01-01

Systems biology, with its associated technologies of proteomics, genomics and metabolomics, is driving the evolution of our understanding of cardiovascular physiology. Rather than studying individual molecules or even single reactions, a systems approach allows integration of orthogonal datasets from distinct tiers of biological data, including gene, RNA, protein, metabolite and other component networks. Together these networks give rise to emergent properties of cellular function and it is their reprogramming that causes disease. We present five observations regarding how systems biology is guiding a revisiting of the central dogma: (i) de-emphasizing the unidirectional flow of information from genes to proteins; (ii) revealing the role of modules of molecules as opposed to individual proteins acting in isolation; (iii) enabling discovery of novel emergent properties; (iv) demonstrating the importance of networks in biology; and (v) adding new dimensionality to the study of biological systems. PMID:22010165

Integrative Transcriptomic Analysis Uncovers Novel Gene Modules That Underlie the Sulfate Response in Arabidopsis thaliana

PubMed Central

Henríquez-Valencia, Carlos; Arenas-M, Anita; Medina, Joaquín; Canales, Javier

2018-01-01

Sulfur is an essential nutrient for plant growth and development. Sulfur is a constituent of proteins, the plasma membrane and cell walls, among other important cellular components. To obtain new insights into the gene regulatory networks underlying the sulfate response, we performed an integrative meta-analysis of transcriptomic data from five different sulfate experiments available in public databases. This bioinformatic approach allowed us to identify a robust set of genes whose expression depends only on sulfate availability, indicating that those genes play an important role in the sulfate response. In relation to sulfate metabolism, the biological function of approximately 45% of these genes is currently unknown. Moreover, we found several consistent Gene Ontology terms related to biological processes that have not been extensively studied in the context of the sulfate response; these processes include cell wall organization, carbohydrate metabolism, nitrogen compound transport, and the regulation of proteolysis. Gene co-expression network analyses revealed relationships between the sulfate-responsive genes that were distributed among seven function-specific co-expression modules. The most connected genes in the sulfate co-expression network belong to a module related to the carbon response, suggesting that this biological function plays an important role in the control of the sulfate response. Temporal analyses of the network suggest that sulfate starvation generates a biphasic response, which involves that major changes in gene expression occur during both the early and late responses. Network analyses predicted that the sulfate response is regulated by a limited number of transcription factors, including MYBs, bZIPs, and NF-YAs. In conclusion, our analysis identified new candidate genes and provided new hypotheses to advance our understanding of the transcriptional regulation of sulfate metabolism in plants. PMID:29692794

Integrative Transcriptomic Analysis Uncovers Novel Gene Modules That Underlie the Sulfate Response in Arabidopsis thaliana.

PubMed

Henríquez-Valencia, Carlos; Arenas-M, Anita; Medina, Joaquín; Canales, Javier

2018-01-01

Sulfur is an essential nutrient for plant growth and development. Sulfur is a constituent of proteins, the plasma membrane and cell walls, among other important cellular components. To obtain new insights into the gene regulatory networks underlying the sulfate response, we performed an integrative meta-analysis of transcriptomic data from five different sulfate experiments available in public databases. This bioinformatic approach allowed us to identify a robust set of genes whose expression depends only on sulfate availability, indicating that those genes play an important role in the sulfate response. In relation to sulfate metabolism, the biological function of approximately 45% of these genes is currently unknown. Moreover, we found several consistent Gene Ontology terms related to biological processes that have not been extensively studied in the context of the sulfate response; these processes include cell wall organization, carbohydrate metabolism, nitrogen compound transport, and the regulation of proteolysis. Gene co-expression network analyses revealed relationships between the sulfate-responsive genes that were distributed among seven function-specific co-expression modules. The most connected genes in the sulfate co-expression network belong to a module related to the carbon response, suggesting that this biological function plays an important role in the control of the sulfate response. Temporal analyses of the network suggest that sulfate starvation generates a biphasic response, which involves that major changes in gene expression occur during both the early and late responses. Network analyses predicted that the sulfate response is regulated by a limited number of transcription factors, including MYBs, bZIPs, and NF-YAs. In conclusion, our analysis identified new candidate genes and provided new hypotheses to advance our understanding of the transcriptional regulation of sulfate metabolism in plants.

[The Biology of Learning].

PubMed

Campo-Cabal, Gerardo

2012-01-01

The effort to relate mental and biological functioning has fluctuated between two doctrines: 1) an attempt to explain mental functioning as a collective property of the brain and 2) as one relatied to other mental processes associated with specific regions of the brain. The article reviews the main theories developed over the last 200 years: phrenology, the psuedo study of the brain, mass action, cellular connectionism and distributed processing among others. In addition, approaches have emerged in recent years that allows for an understanding of the biological determinants and individual differences in complex mental processes through what is called cognitive neuroscience. Knowing the definition of neuroscience, the learning of memory, the ways in which learning occurs, the principles of the neural basis of memory and learning and its effects on brain function, among other things, allows us the basic understanding of the processes of memory and learning and is an important requirement to address the best manner to commit to the of training future specialists in Psychiatry. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Paracrystalline Disorder from Phosphate Ion Orientation and Substitution in Synthetic Bone Mineral

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

Marisa, Mary E.; Zhou, Shiliang; Melot, Brent C.

Hydroxyapatite is an inorganic mineral closely resembling the mineral phase in bone. However, as a biological mineral, it is highly disordered, and its composition and atomistic structure remain poorly understood. Here, synchrotron X-ray total scattering and pair distribution function analysis methods provide insight into the nature of atomistic disorder in a synthetic bone mineral analogue, chemically substituted hydroxyapatite. By varying the effective hydrolysis rate and/or carbonate concentration during growth of the mineral, compounds with varied degrees of paracrystallinity are prepared. From advanced simulations constrained by the experimental pair distribution function and density functional theory, the paracrystalline disorder prevalent in thesemore » materials appears to result from accommodation of carbonate in the lattice through random displacement of the phosphate groups. Though many substitution modalities are likely to occur in concert, the most predominant substitution places carbonate into the mirror plane of an ideal phosphate site. Understanding the mineralogical imperfections of a biologically analogous hydroxyapatite is important not only to potential bone grafting applications but also to biological mineralization processes themselves.« less

Bio-hybrid cell-based actuators for microsystems.

PubMed

Carlsen, Rika Wright; Sitti, Metin

2014-10-15

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

Self-restoration as fundamental property of CES providing their sustainability

NASA Astrophysics Data System (ADS)

Gitelson, I. I.; Degermendzhy, A. G.; Rodicheva, E. K.

Sustainability is one of the most important criteria in the creation and evaluation of human life support systems intended for use during long space flights. The common feature of biological and physicochemical life support systems is that basically they are both catalytic. But there are two fundamental properties distinguishing biological systems: 1) they are auto-catalytic: their catalysts — enzymes of protein nature — are continuously reproduced when the system functions; 2) the program of every process performed by enzymes and the program of their reproduction are inherent in the biological system itself — in the totality of genomes of the species involved in the functioning of the ecosystem. Actually, one cell with the genome capable of the phenotypic realization is enough for the self-restoration of the function performed by the cells of this species in the ecosystem. The continuous microalgal culture of Chlorella vulgaris was taken to investigate quantitatively the process of self-restoration in unicellular algae population. Based on the data obtained, we proposed a mathematical model of the restoration process in a cell population that has suffered an acute radiation damage.

Scavenger Receptors: Emerging Roles in Cancer Biology and Immunology

PubMed Central

Yu, Xiaofei; Guo, Chunqing; Fisher, Paul B.; Subjeck, John R.; Wang, Xiang-Yang

2015-01-01

Scavenger receptors constitute a large family of evolutionally conserved protein molecules that are structurally and functionally diverse. Although scavenger receptors were originally identified based on their capacity to scavenge modified lipoproteins, these molecules have been shown to recognize and bind to a broad spectrum of ligands, including modified and unmodified host-derived molecules or microbial components. As a major subset of innate pattern recognition receptors, scavenger receptors are mainly expressed on myeloid cells and function in a wide range of biological processes, such as endocytosis, adhesion, lipid transport, antigen presentation, and pathogen clearance. In addition to playing a crucial role in maintenance of host homeostasis, scavenger receptors have been implicated in the pathogenesis of a number of diseases, e.g., atherosclerosis, neurodegeneration, or metabolic disorders. Emerging evidence has begun to reveal these receptor molecules as important regulators of tumor behavior and host immune responses to cancer. This review summarizes our current understanding on the newly identified, distinct functions of scavenger receptors in cancer biology and immunology. The potential of scavenger receptors as diagnostic biomarkers and novel targets for therapeutic interventions to treat malignancies is also highlighted. PMID:26216637

The Sertoli cell: one hundred fifty years of beauty and plasticity

PubMed Central

França, L. R.; Hess, R. A.; Dufour, J. M.; Hofmann, M. C.; Griswold, M. D.

2017-01-01

SUMMARY It has been one and a half centuries since Enrico Sertoli published the seminal discovery of the testicular ‘nurse cell’, not only a key cell in the testis, but indeed one of the most amazing cells in the vertebrate body. In this review, we begin by examining the three phases of morphological research that have occurred in the study of Sertoli cells, because microscopic anatomy was essentially the only scientific discipline available for about the first 75 years after the discovery. Biochemistry and molecular biology then changed all of biological sciences, including our understanding of the functions of Sertoli cells. Immunology and stem cell biology were not even topics of science in 1865, but they have now become major issues in our appreciation of Sertoli cell’s role in spermatogenesis. We end with the universal importance and plasticity of function by comparing Sertoli cells in fish, amphibians, and mammals. In these various classes of vertebrates, Sertoli cells have quite different modes of proliferation and epithelial maintenance, cystic vs. tubular formation, yet accomplish essentially the same function but in strikingly different ways. PMID:26846984

MicroRNAs from the Planarian Schmidtea mediterranea: a model system for stem cell biology.

PubMed

Palakodeti, Dasaradhi; Smielewska, Magda; Graveley, Brenton R

2006-09-01

MicroRNAs (miRNAs) are approximately 22-nt RNA molecules that typically bind to the 3' untranslated regions of target mRNAs and function to either induce mRNA degradation or repress translation. miRNAs have been shown to play important roles in the function of stem cells and cell lineage decisions in a variety of organisms, including humans. Planarians are bilaterally symmetric metazoans that have the unique ability to completely regenerate lost tissues or organs. This regenerative capacity is facilitated by a population of stem cells known as neoblasts. Planarians are therefore an excellent model system for studying many aspects of stem cell biology. Here we report the cloning and initial characterization of 71 miRNAs from the planarian Schmidtea mediterranea. While several of the S. mediterranea miRNAs are members of miRNA families identified in other species, we also identified a number of planarian-specific miRNAs. This work lays the foundation for functional studies aimed at addressing the role of these miRNAs in regeneration, cell lineage decisions, and basic stem cell biology.

Synergy among Microbiota and Their Hosts: Leveraging the Hawaiian Archipelago and Local Collaborative Networks To Address Pressing Questions in Microbiome Research

PubMed Central

Frank, Kiana L.; Alegado, Rosanna A.; Amend, Anthony S.; Arif, Mohammad; Bennett, Gordon M.; Jani, Andrea J.; Medeiros, Matthew C. I.; Mileyko, Yuriy; Nguyen, Nhu H.; Nigro, Olivia D.; Prisic, Sladjana; Shin, Sangwoo; Takagi, Daisuke; Wilson, Samuel T.; Yew, Joanne Y.

2018-01-01

ABSTRACT Despite increasing acknowledgment that microorganisms underpin the healthy functioning of basically all multicellular life, few cross-disciplinary teams address the diversity and function of microbiota across organisms and ecosystems. Our newly formed consortium of junior faculty spanning fields such as ecology and geoscience to mathematics and molecular biology from the University of Hawai‘i at Mānoa aims to fill this gap. We are united in our mutual interest in advancing a new paradigm for biology that incorporates our modern understanding of the importance of microorganisms. As our first concerted research effort, we will assess the diversity and function of microbes across an entire watershed on the island of Oahu, Hawai‘i. Due to its high ecological diversity across tractable areas of land and sea, Hawai‘i provides a model system for the study of complex microbial communities and the processes they mediate. Owing to our diverse expertise, we will leverage this study system to advance the field of biology. PMID:29556540

Primary cilia proteins: ciliary and extraciliary sites and functions.

PubMed

Hua, Kiet; Ferland, Russell J

2018-05-01

Primary cilia are immotile organelles known for their roles in development and cell signaling. Defects in primary cilia result in a range of disorders named ciliopathies. Because this organelle can be found singularly on almost all cell types, its importance extends to most organ systems. As such, elucidating the importance of the primary cilium has attracted researchers from all biological disciplines. As the primary cilia field expands, caution is warranted in attributing biological defects solely to the function of this organelle, since many of these "ciliary" proteins are found at other sites in cells and likely have non-ciliary functions. Indeed, many, if not all, cilia proteins have locations and functions outside the primary cilium. Extraciliary functions are known to include cell cycle regulation, cytoskeletal regulation, and trafficking. Cilia proteins have been observed in the nucleus, at the Golgi apparatus, and even in immune synapses of T cells (interestingly, a non-ciliated cell). Given the abundance of extraciliary sites and functions, it can be difficult to definitively attribute an observed phenotype solely to defective cilia rather than to some defective extraciliary function or a combination of both. Thus, extraciliary sites and functions of cilia proteins need to be considered, as well as experimentally determined. Through such consideration, we will understand the true role of the primary cilium in disease as compared to other cellular processes' influences in mediating disease (or through a combination of both). Here, we review a compilation of known extraciliary sites and functions of "cilia" proteins as a means to demonstrate the potential non-ciliary roles for these proteins.

Studies of the structure-activity relationships of peptides and proteins involved in growth and development based on their three-dimensional structures.

PubMed

Nagata, Koji

2010-01-01

Peptides and proteins with similar amino acid sequences can have different biological functions. Knowledge of their three-dimensional molecular structures is critically important in identifying their functional determinants. In this review, I describe the results of our and other groups' structure-based functional characterization of insect insulin-like peptides, a crustacean hyperglycemic hormone-family peptide, a mammalian epidermal growth factor-family protein, and an intracellular signaling domain that recognizes proline-rich sequence.

[P21-activated kinases and their role in the nervous system].

PubMed

Qin, Yuan; Ding, Yue-Min; Xia, Qiang

2012-12-25

P21-activated kinases (PAK) participate in a variety of important cellular activities, such as cytoskeleton remodeling, cell migration, cell cycle regulation, and apoptosis or survival. PAK also has an important impact on brain development, neuronal differentiation, and regulation of synaptic plasticity in the nervous system. PAK abnormalities result in diseases including cancer, Parkinson's disease (PD), Alzheimer's disease (AD) and neural retardation. Therefore, it is of vital physiological significance to investigate the neuronal function of PAK. In this paper we review the advancement of research on the neuronal biological function and the underlying mechanisms of PAK.

Downregulation of the expression of HDGF attenuates malignant biological behaviors of hilar cholangiocarcinoma cells.

PubMed

Liu, Yanfeng; Sun, Jingxian; Yang, Guangyun; Liu, Zhaojian; Guo, Sen; Zhao, Rui; Xu, Kesen; Wu, Xiaopeng; Zhang, Zhaoyang

2015-09-01

Hepatoma-derived growth factor (HDGF) has been reported to be a potential predictive and prognostic marker for several types of cancer and important in malignant biological behaviors. However, its role in human hilar cholangiocarcinoma remains to be elucidated. Our previous study demonstrated that high expression levels of HDGF in hilar cholangiocarcinoma tissues correlates with tumor progression and patient outcome. The present study aimed to elucidate the detailed functions of the HDGF protein. This was performed by downregulating the protein expression of HDGF in the FRH0201 hilar cholangiocarcinoma cell line by RNA interference (RNAi) in vitro, and revealed that downregulation of the HDGF protein significantly inhibited the malignant biological behavior of the FRH0201 cells. In addition, further investigation revealed that downregulation of the protein expression of HDGF significantly decreased the secretion of vascular endothelial growth factor, which may be the mechanism partially responsible for the inhibition of malignant biological behaviors. These findings demonstrated that HDGF is important in promoting malignant biological behaviors, including proliferation, migration and invasion of hilar cholangiocarcinoma FRH0201 cells. Inhibition of the expression of HDGF downregulated the malignant biological behaviors, suggesting that downregulation of the protein expression of HDGF by RNAi may be a novel therapeutic approach to inhibit the progression of hilar cholangiocarcinoma.

Considerations for designing chemical screening strategies in plant biology

PubMed Central

Serrano, Mario; Kombrink, Erich; Meesters, Christian

2015-01-01

Traditionally, biologists regularly used classical genetic approaches to characterize and dissect plant processes. However, this strategy is often impaired by redundancy, lethality or pleiotropy of gene functions, which prevent the isolation of viable mutants. The chemical genetic approach has been recognized as an alternative experimental strategy, which has the potential to circumvent these problems. It relies on the capacity of small molecules to modify biological processes by specific binding to protein target(s), thereby conditionally modifying protein function(s), which phenotypically resemble mutation(s) of the encoding gene(s). A successful chemical screening campaign comprises three equally important elements: (1) a reliable, robust, and quantitative bioassay, which allows to distinguish between potent and less potent compounds, (2) a rigorous validation process for candidate compounds to establish their selectivity, and (3) an experimental strategy for elucidating a compound's mode of action and molecular target. In this review we will discuss details of this general strategy and additional aspects that deserve consideration in order to take full advantage of the power provided by the chemical approach to plant biology. In addition, we will highlight some success stories of recent chemical screenings in plant systems, which may serve as teaching examples for the implementation of future chemical biology projects. PMID:25904921

Urinary long noncoding RNAs in nonmuscle-invasive bladder cancer: new architects in cancer prognostic biomarkers.

PubMed

Terracciano, Daniela; Ferro, Matteo; Terreri, Sara; Lucarelli, Giuseppe; D'Elia, Carolina; Musi, Gennaro; de Cobelli, Ottavio; Mirone, Vincenzo; Cimmino, Amelia

2017-06-01

Several reports over the last 10 years provided evidence that long noncoding RNAs (lncRNAs) are often altered in bladder cancers. lncRNAs are longer than 200 nucleotides and function as important regulators of gene expression, interacting with the major pathways of cell growth, proliferation, differentiation, and survival. A large number of lncRNAs has oncogenic function and is more expressed in tumor compared with normal tissues. Their overexpression may be associated with tumor formation, progression, and metastasis in a variety of tumors including bladder cancer. Although lncRNAs have been shown to have critical regulatory roles in cancer biology, the biological functions and prognostic values in nonmuscle-invasive bladder cancer remain largely unknown. Nevertheless, a growing body of evidence suggests that several lncRNAs expression profiles in bladder malignancies are associated with poor prognosis, and they can be detected in biological fluids, such as urines. Here, we review current progress in the biology and the implication of lncRNAs associated with bladder cancer, and we discuss their potential use as diagnosis and prognosis biomarkers in bladder malignancies with a focus on their role in high-risk nonmuscle-invasive tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

Modelling the Impact of Soil Management on Soil Functions

NASA Astrophysics Data System (ADS)

Vogel, H. J.; Weller, U.; Rabot, E.; Stößel, B.; Lang, B.; Wiesmeier, M.; Urbanski, L.; Wollschläger, U.

2017-12-01

Due to an increasing soil loss and an increasing demand for food and energy there is an enormous pressure on soils as the central resource for agricultural production. Besides the importance of soils for biomass production there are other essential soil functions, i.e. filter and buffer for water, carbon sequestration, provision and recycling of nutrients, and habitat for biological activity. All these functions have a direct feed back to biogeochemical cycles and climate. To render agricultural production efficient and sustainable we need to develop model tools that are capable to predict quantitatively the impact of a multitude of management measures on these soil functions. These functions are considered as emergent properties produced by soils as complex systems. The major challenge is to handle the multitude of physical, chemical and biological processes interacting in a non-linear manner. A large number of validated models for specific soil processes are available. However, it is not possible to simulate soil functions by coupling all the relevant processes at the detailed (i.e. molecular) level where they are well understood. A new systems perspective is required to evaluate the ensemble of soil functions and their sensitivity to external forcing. Another challenge is that soils are spatially heterogeneous systems by nature. Soil processes are highly dependent on the local soil properties and, hence, any model to predict soil functions needs to account for the site-specific conditions. For upscaling towards regional scales the spatial distribution of functional soil types need to be taken into account. We propose a new systemic model approach based on a thorough analysis of the interactions between physical, chemical and biological processes considering their site-specific characteristics. It is demonstrated for the example of soil compaction and the recovery of soil structure, water capacity and carbon stocks as a result of plant growth and biological activity. Coupling of the observed nonlinear interactions allows for modeling the stability and resilience of soil systems in terms of their essential functions.

Incorporating surrogate species and seascape connectivity to improve marine conservation outcomes.

PubMed

Olds, Andrew D; Connolly, Rod M; Pitt, Kylie A; Maxwell, Paul S; Aswani, Shankar; Albert, Simon

2014-08-01

Conservation focuses on maintaining biodiversity and ecosystem functioning, but gaps in our knowledge of species biology and ecological processes often impede progress. For this reason, focal species and habitats are used as surrogates for multispecies conservation, but species-based approaches are not widely adopted in marine ecosystems. Reserves in the Solomon Islands were designed on the basis of local ecological knowledge to conserve bumphead parrotfish (Bolbometopon muricatum) and to protect food security and ecosystem functioning. Bumphead parrotfish are an iconic threatened species and may be a useful surrogate for multispecies conservation. They move across tropical seascapes throughout their life history, in a pattern of habitat use that is shared with many other species. We examined their value as a conservation surrogate and assessed the importance of seascape connectivity (i.e., the physical connectedness of patches in the seascape) among reefs, mangroves, and seagrass to marine reserve performance. Reserves were designed for bumphead parrotfish, but also enhanced the abundance of other species. Integration of local ecological knowledge and seascape connectivity enhanced the abundance of 17 other harvested fish species in local reserves. This result has important implications for ecosystem functioning and local villagers because many of these species perform important ecological processes and provide the foundation for extensive subsistence fisheries. Our findings suggest greater success in maintaining and restoring marine ecosystems may be achieved when they are managed to conserve surrogate species and preserve functional seascape connections. © 2014 Society for Conservation Biology.

F-BAR family proteins, emerging regulators for cell membrane dynamic changes-from structure to human diseases.

PubMed

Liu, Suxuan; Xiong, Xinyu; Zhao, Xianxian; Yang, Xiaofeng; Wang, Hong

2015-05-09

Eukaryotic cell membrane dynamics change in curvature during physiological and pathological processes. In the past ten years, a novel protein family, Fes/CIP4 homology-Bin/Amphiphysin/Rvs (F-BAR) domain proteins, has been identified to be the most important coordinators in membrane curvature regulation. The F-BAR domain family is a member of the Bin/Amphiphysin/Rvs (BAR) domain superfamily that is associated with dynamic changes in cell membrane. However, the molecular basis in membrane structure regulation and the biological functions of F-BAR protein are unclear. The pathophysiological role of F-BAR protein is unknown. This review summarizes the current understanding of structure and function in the BAR domain superfamily, classifies F-BAR family proteins into nine subfamilies based on domain structure, and characterizes F-BAR protein structure, domain interaction, and functional relevance. In general, F-BAR protein binds to cell membrane via F-BAR domain association with membrane phospholipids and initiates membrane curvature and scission via Src homology-3 (SH3) domain interaction with its partner proteins. This process causes membrane dynamic changes and leads to seven important cellular biological functions, which include endocytosis, phagocytosis, filopodium, lamellipodium, cytokinesis, adhesion, and podosome formation, via distinct signaling pathways determined by specific domain-binding partners. These cellular functions play important roles in many physiological and pathophysiological processes. We further summarize F-BAR protein expression and mutation changes observed in various diseases and developmental disorders. Considering the structure feature and functional implication of F-BAR proteins, we anticipate that F-BAR proteins modulate physiological and pathophysiological processes via transferring extracellular materials, regulating cell trafficking and mobility, presenting antigens, mediating extracellular matrix degradation, and transmitting signaling for cell proliferation.

Macroscopic Biological Characteristics of Individualized Therapy in Chinese Mongolian Osteopathy

NASA Astrophysics Data System (ADS)

Namula, Zhao; Mei, Wang; Li, Xue-en

Objective: Chinese Mongolian osteopathy has been passed down from ancient times and includes unique practices and favorable efficacy. In this study, we investigate the macroscopic biological characteristics of individualized Chinese Mongolian osteopathy, in order to provide new principle and methods for the treatment of bone fracture. Method: With a view to provide a vital link between nature and humans, the four stages of Chinese Mongolian osteopathy focus on the unity of the mind and body, the limbs and body organs, the body and its functions, and humans and nature. Results: We discuss the merits of individualized osteopathy in terms of the underlying concepts, and evaluate the approaches and principles of traditional medicine, as well as biomechanics. Conclusions: Individualized Mongolian osteopathy targets macroscopic biological components including dynamic reduction, natural fixation, and functional healing. Chinese Mongolian osteopathy is a natural, ecological and non-invasive osteopathy that values the link between nature and humans, including the unity of mind and body. The biological components not only serve as a foundation for Chinese Mongolian osteopathy but are also important for the future development of modern osteopathy, focusing on individualization, actualization and integration.

AIM: A comprehensive Arabidopsis Interactome Module database and related interologs in plants

USDA-ARS?s Scientific Manuscript database

Systems biology analysis of protein modules is important for understanding the functional relationships between proteins in the interactome. Here, we present a comprehensive database named AIM for Arabidopsis (Arabidopsis thaliana) interactome modules. The database contains almost 250,000 modules th...

Neoproteoglycans in tissue engineering.

PubMed

Weyers, Amanda; Linhardt, Robert J

2013-05-01

Proteoglycans, comprised of a core protein to which glycosaminoglycan chains are covalently linked, are an important structural and functional family of macromolecules found in the extracellular matrix. Advances in our understanding of biological interactions have lead to a greater appreciation for the need to design tissue engineering scaffolds that incorporate mimetics of key extracellular matrix components. A variety of synthetic and semisynthetic molecules and polymers have been examined by tissue engineers that serve as structural, chemical and biological replacements for proteoglycans. These proteoglycan mimetics have been referred to as neoproteoglycans and serve as functional and therapeutic replacements for natural proteoglycans that are often unavailable for tissue engineering studies. Although neoproteoglycans have important limitations, such as limited signaling ability and biocompatibility, they have shown promise in replacing the natural activity of proteoglycans through cell and protein binding interactions. This review focuses on the recent in vivo and in vitro tissue engineering applications of three basic types of neoproteoglycan structures, protein-glycosaminoglycan conjugates, nano-glycosaminoglycan composites and polymer-glycosaminoglycan complexes. © 2013 The Authors Journal compilation © 2013 FEBS.

Neoproteoglycans in tissue engineering

PubMed Central

Weyers, Amanda; Linhardt, Robert J.

2014-01-01

Proteoglycans, comprised of a core protein to which glycosaminoglycan chains are covalently linked, are an important structural and functional family of macromolecules found in the extracellular matrix. Advances in our understanding of biological interactions have lead to a greater appreciation for the need to design tissue engineering scaffolds that incorporate mimetics of key extracellular matrix components. A variety of synthetic and semisynthetic molecules and polymers have been examined by tissue engineers that serve as structural, chemical and biological replacements for proteoglycans. These proteoglycan mimetics have been referred to as neoproteoglycans and serve as functional and therapeutic replacements for natural proteoglycans that are often unavailable for tissue engineering studies. Although neoproteoglycans have important limitations, such as limited signaling ability and biocompatibility, they have shown promise in replacing the natural activity of proteoglycans through cell and protein binding interactions. This review focuses on the recent in vivo and in vitro tissue engineering applications of three basic types of neoproteoglycan structures, protein–glycosaminoglycan conjugates, nano-glycosaminoglycan composites and polymer–glycosaminoglycan complexes. PMID:23399318

From Network Analysis to Functional Metabolic Modeling of the Human Gut Microbiota.

PubMed

Bauer, Eugen; Thiele, Ines

2018-01-01

An important hallmark of the human gut microbiota is its species diversity and complexity. Various diseases have been associated with a decreased diversity leading to reduced metabolic functionalities. Common approaches to investigate the human microbiota include high-throughput sequencing with subsequent correlative analyses. However, to understand the ecology of the human gut microbiota and consequently design novel treatments for diseases, it is important to represent the different interactions between microbes with their associated metabolites. Computational systems biology approaches can give further mechanistic insights by constructing data- or knowledge-driven networks that represent microbe interactions. In this minireview, we will discuss current approaches in systems biology to analyze the human gut microbiota, with a particular focus on constraint-based modeling. We will discuss various community modeling techniques with their advantages and differences, as well as their application to predict the metabolic mechanisms of intestinal microbial communities. Finally, we will discuss future perspectives and current challenges of simulating realistic and comprehensive models of the human gut microbiota.

From Saccharomyces cerevisiae to human: The important gene co-expression modules.

PubMed

Liu, Wei; Li, Li; Ye, Hua; Chen, Haiwei; Shen, Weibiao; Zhong, Yuexian; Tian, Tian; He, Huaqin

2017-08-01

Network-based systems biology has become an important method for analyzing high-throughput gene expression data and gene function mining. Yeast has long been a popular model organism for biomedical research. In the current study, a weighted gene co-expression network analysis algorithm was applied to construct a gene co-expression network in Saccharomyces cerevisiae . Seventeen stable gene co-expression modules were detected from 2,814 S. cerevisiae microarray data. Further characterization of these modules with the Database for Annotation, Visualization and Integrated Discovery tool indicated that these modules were associated with certain biological processes, such as heat response, cell cycle, translational regulation, mitochondrion oxidative phosphorylation, amino acid metabolism and autophagy. Hub genes were also screened by intra-modular connectivity. Finally, the module conservation was evaluated in a human disease microarray dataset. Functional modules were identified in budding yeast, some of which are associated with patient survival. The current study provided a paradigm for single cell microorganisms and potentially other organisms.

Mathematical and Computational Modeling in Complex Biological Systems

PubMed Central

Li, Wenyang; Zhu, Xiaoliang

2017-01-01

The biological process and molecular functions involved in the cancer progression remain difficult to understand for biologists and clinical doctors. Recent developments in high-throughput technologies urge the systems biology to achieve more precise models for complex diseases. Computational and mathematical models are gradually being used to help us understand the omics data produced by high-throughput experimental techniques. The use of computational models in systems biology allows us to explore the pathogenesis of complex diseases, improve our understanding of the latent molecular mechanisms, and promote treatment strategy optimization and new drug discovery. Currently, it is urgent to bridge the gap between the developments of high-throughput technologies and systemic modeling of the biological process in cancer research. In this review, we firstly studied several typical mathematical modeling approaches of biological systems in different scales and deeply analyzed their characteristics, advantages, applications, and limitations. Next, three potential research directions in systems modeling were summarized. To conclude, this review provides an update of important solutions using computational modeling approaches in systems biology. PMID:28386558

Mathematical and Computational Modeling in Complex Biological Systems.

PubMed

Ji, Zhiwei; Yan, Ke; Li, Wenyang; Hu, Haigen; Zhu, Xiaoliang

2017-01-01

The biological process and molecular functions involved in the cancer progression remain difficult to understand for biologists and clinical doctors. Recent developments in high-throughput technologies urge the systems biology to achieve more precise models for complex diseases. Computational and mathematical models are gradually being used to help us understand the omics data produced by high-throughput experimental techniques. The use of computational models in systems biology allows us to explore the pathogenesis of complex diseases, improve our understanding of the latent molecular mechanisms, and promote treatment strategy optimization and new drug discovery. Currently, it is urgent to bridge the gap between the developments of high-throughput technologies and systemic modeling of the biological process in cancer research. In this review, we firstly studied several typical mathematical modeling approaches of biological systems in different scales and deeply analyzed their characteristics, advantages, applications, and limitations. Next, three potential research directions in systems modeling were summarized. To conclude, this review provides an update of important solutions using computational modeling approaches in systems biology.

Organellar proteomics reveals hundreds of novel nuclear proteins in the malaria parasite Plasmodium falciparum

PubMed Central

2012-01-01

Background The post-genomic era of malaria research provided unprecedented insights into the biology of Plasmodium parasites. Due to the large evolutionary distance to model eukaryotes, however, we lack a profound understanding of many processes in Plasmodium biology. One example is the cell nucleus, which controls the parasite genome in a development- and cell cycle-specific manner through mostly unknown mechanisms. To study this important organelle in detail, we conducted an integrative analysis of the P. falciparum nuclear proteome. Results We combined high accuracy mass spectrometry and bioinformatic approaches to present for the first time an experimentally determined core nuclear proteome for P. falciparum. Besides a large number of factors implicated in known nuclear processes, one-third of all detected proteins carry no functional annotation, including many phylum- or genus-specific factors. Importantly, extensive experimental validation using 30 transgenic cell lines confirmed the high specificity of this inventory, and revealed distinct nuclear localization patterns of hitherto uncharacterized proteins. Further, our detailed analysis identified novel protein domains potentially implicated in gene transcription pathways, and sheds important new light on nuclear compartments and processes including regulatory complexes, the nucleolus, nuclear pores, and nuclear import pathways. Conclusion Our study provides comprehensive new insight into the biology of the Plasmodium nucleus and will serve as an important platform for dissecting general and parasite-specific nuclear processes in malaria parasites. Moreover, as the first nuclear proteome characterized in any protist organism, it will provide an important resource for studying evolutionary aspects of nuclear biology. PMID:23181666

Gene Mining for Proline Based Signaling Proteins in Cell Wall of Arabidopsis thaliana

PubMed Central

Ihsan, Muhammad Z.; Ahmad, Samina J. N.; Shah, Zahid Hussain; Rehman, Hafiz M.; Aslam, Zubair; Ahuja, Ishita; Bones, Atle M.; Ahmad, Jam N.

2017-01-01

The cell wall (CW) as a first line of defense against biotic and abiotic stresses is of primary importance in plant biology. The proteins associated with cell walls play a significant role in determining a plant's sustainability to adverse environmental conditions. In this work, the genes encoding cell wall proteins (CWPs) in Arabidopsis were identified and functionally classified using geneMANIA and GENEVESTIGATOR with published microarrays data. This yielded 1605 genes, out of which 58 genes encoded proline-rich proteins (PRPs) and glycine-rich proteins (GRPs). Here, we have focused on the cellular compartmentalization, biological processes, and molecular functioning of proline-rich CWPs along with their expression at different plant developmental stages. The mined genes were categorized into five classes on the basis of the type of PRPs encoded in the cell wall of Arabidopsis thaliana. We review the domain structure and function of each class of protein, many with respect to the developmental stages of the plant. We have then used networks, hierarchical clustering and correlations to analyze co-expression, co-localization, genetic, and physical interactions and shared protein domains of these PRPs. This has given us further insight into these functionally important CWPs and identified a number of potentially new cell-wall related proteins in A. thaliana. PMID:28289422

A Systems Biology Approach to Synovial Joint Lubrication in Health, Injury, and Disease

PubMed Central

Hui, Alexander Y.; McCarty, William J.; Masuda, Koichi; Firestein, Gary S.; Sah, Robert L.

2013-01-01

The synovial joint contains synovial fluid (SF) within a cavity bounded by articular cartilage and synovium. SF is a viscous fluid that has lubrication, metabolic, and regulatory functions within synovial joints. SF contains lubricant molecules, including proteoglycan-4 and hyaluronan. SF is an ultrafiltrate of plasma with secreted contributions from cell populations lining and within the synovial joint space, including chondrocytes and synoviocytes. Maintenance of normal SF lubricant composition and function are important for joint homeostasis. In osteoarthritis, rheumatoid arthritis, and joint injury, changes in lubricant composition and function accompany alterations in the cytokine and growth factor environment and increased fluid and molecular transport through joint tissues. Thus, understanding the synovial joint lubrication system requires a multi-faceted study of the various parts of the synovial joint and their interactions. Systems biology approaches at multiple scales are being used to describe the molecular, cellular, and tissue components and their interactions that comprise the functioning synovial joint. Analyses of the transcriptome and proteome of SF, cartilage, and synovium suggest that particular molecules and pathways play important roles in joint homeostasis and disease. Such information may be integrated with physicochemical tissue descriptions to construct integrative models of the synovial joint that ultimately may explain maintenance of health, recovery from injury, or development and progression of arthritis. PMID:21826801

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

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

Getting the most out of parasitic helminth transcriptomes using HelmDB: implications for biology and biotechnology.

PubMed

Mangiola, Stefano; Young, Neil D; Korhonen, Pasi; Mondal, Alinda; Scheerlinck, Jean-Pierre; Sternberg, Paul W; Cantacessi, Cinzia; Hall, Ross S; Jex, Aaron R; Gasser, Robin B

2013-12-01

Compounded by a massive global food shortage, many parasitic diseases have a devastating, long-term impact on animal and human health and welfare worldwide. Parasitic helminths (worms) affect the health of billions of animals. Unlocking the systems biology of these neglected pathogens will underpin the design of new and improved interventions against them. Currently, the functional annotation of genomic and transcriptomic sequence data for socio-economically important parasitic worms relies almost exclusively on comparative bioinformatic analyses using model organism- and other databases. However, many genes and gene products of parasitic helminths (often >50%) cannot be annotated using this approach, because they are specific to parasites and/or do not have identifiable homologs in other organisms for which sequence data are available. This inability to fully annotate transcriptomes and predicted proteomes is a major challenge and constrains our understanding of the biology of parasites, interactions with their hosts and of parasitism and the pathogenesis of disease on a molecular level. In the present article, we compiled transcriptomic data sets of key, socioeconomically important parasitic helminths, and constructed and validated a curated database, called HelmDB (www.helmdb.org). We demonstrate how this database can be used effectively for the improvement of functional annotation by employing data integration and clustering. Importantly, HelmDB provides a practical and user-friendly toolkit for sequence browsing and comparative analyses among divergent helminth groups (including nematodes and trematodes), and should be readily adaptable and applicable to a wide range of other organisms. This web-based, integrative database should assist 'systems biology' studies of parasitic helminths, and the discovery and prioritization of novel drug and vaccine targets. This focus provides a pathway toward developing new and improved approaches for the treatment and control of parasitic diseases, with the potential for important biotechnological outcomes. Copyright © 2012 Elsevier Inc. All rights reserved.

United States Department of Agriculture-Agricultural Research Service: advances in the molecular genetic analysis of insects and their application to pest management.

PubMed

Handler, Alfred M; Beeman, Richard W

2003-01-01

USDA-ARS scientists have made important contributions to the molecular genetic analysis of agriculturally important insects, and have been in the forefront of using this information for the development of new pest management strategies. Advances have been made in the identification and analysis of genetic systems involved in insect development, reproduction and behavior which enable the identification of new targets for control, as well as the development of highly specific insecticidal products. Other studies have been on the leading edge of developing gene transfer technology to better elucidate these biological processes though functional genomics and to develop new transgenic strains for biological control. Important contributions have also been made to the development and use of molecular markers and methodologies to identify and track insect populations. The use of molecular genetic technology and strategies will become increasingly important to pest management as genomic sequencing information becomes available from important pest insects, their targets and other associated organisms.

Ligand binding induces a sharp decrease in hydrophobicity of folate binding protein assessed by 1-anilinonaphthalene-8-sulphonate which suppresses self-association of the hydrophobic apo-protein.

PubMed

Holm, Jan; Lawaetz, Anders J; Hansen, Steen I

2012-08-17

High affinity folate binding protein (FBP) regulates as a soluble protein and as a cellular receptor intracellular trafficking of folic acid, a vitamin of great importance to cell growth and division. We addressed two issues of potential importance to the biological function of FBP, a possible decrease of the surface hydrophobicity associated with the ligand-induced conformation change of FBP, and protein-inter-protein interactions involved in self-association of hydrophobic apo-FBP. The extrinsic fluorescent apolar dye 1-anilinonaphthalene-8-sulphonate (ANS) exhibited enhanced fluorescence intensity and a blueshift of emission maximum from 510-520 nm to 460-470 nm upon addition of apo-FBP indicating binding to a strongly hydrophobic environment. Neither enhancement of fluorescence nor blueshift of ANS emission maximum occurred when folate-ligated holo-FBP replaced apo-FBP. The drastic decrease in surface hydrophobicity of holo-FBP could have bearings on the biological function of FBP since changes in surface hydrophobicity have critical effects on the biological function of receptors and transport proteins. ANS interacts with exposed hydrophobic surfaces on proteins and may thereby block and prevent aggregation of proteins (chaperone-like effect). Hence, hydrophobic interactions seemed to participate in the concentration-dependent self-association of apo-FBP which was suppressed by high ANS concentrations in light scatter measurements. Copyright © 2012 Elsevier Inc. All rights reserved.

Step-by-Step Simulation of Radiation Chemistry Using Green Functions for Diffusion-Influenced Reactions

NASA Technical Reports Server (NTRS)

Plante, Ianik; Cucinotta, Francis A.

2011-01-01

Radiolytic species are formed approximately 1 ps after the passage of ionizing radiation through matter. After their formation, they diffuse and chemically react with other radiolytic species and neighboring biological molecules, leading to various oxidative damage. Therefore, the simulation of radiation chemistry is of considerable importance to understand how radiolytic species damage biological molecules [1]. The step-by-step simulation of chemical reactions is difficult, because the radiolytic species are distributed non-homogeneously in the medium. Consequently, computational approaches based on Green functions for diffusion-influenced reactions should be used [2]. Recently, Green functions for more complex type of reactions have been published [3-4]. We have developed exact random variate generators of these Green functions [5], which will allow us to use them in radiation chemistry codes. Moreover, simulating chemistry using the Green functions is which is computationally very demanding, because the probabilities of reactions between each pair of particles should be evaluated at each timestep [2]. This kind of problem is well adapted for General Purpose Graphic Processing Units (GPGPU), which can handle a large number of similar calculations simultaneously. These new developments will allow us to include more complex reactions in chemistry codes, and to improve the calculation time. This code should be of importance to link radiation track structure simulations and DNA damage models.

Evolution and development of model membranes for physicochemical and functional studies of the membrane lateral heterogeneity.

PubMed

Morigaki, Kenichi; Tanimoto, Yasushi

2018-03-14

One of the main questions in the membrane biology is the functional roles of membrane heterogeneity and molecular localization. Although segregation and local enrichment of protein/lipid components (rafts) have been extensively studied, the presence and functions of such membrane domains still remain elusive. Along with biochemical, cell observation, and simulation studies, model membranes are emerging as an important tool for understanding the biological membrane, providing quantitative information on the physicochemical properties of membrane proteins and lipids. Segregation of fluid lipid bilayer into liquid-ordered (Lo) and liquid-disordered (Ld) phases has been studied as a simplified model of raft in model membranes, including giant unilamellar vesicles (GUVs), giant plasma membrane vesicles (GPMVs), and supported lipid bilayers (SLB). Partition coefficients of membrane proteins between Lo and Ld phases were measured to gauze their affinities to lipid rafts (raftophilicity). One important development in model membrane is patterned SLB based on the microfabrication technology. Patterned Lo/Ld phases have been applied to study the partition and function of membrane-bound molecules. Quantitative information of individual molecular species attained by model membranes is critical for elucidating the molecular functions in the complex web of molecular interactions. The present review gives a short account of the model membranes developed for studying the lateral heterogeneity, especially focusing on patterned model membranes on solid substrates. Copyright © 2018 Elsevier B.V. All rights reserved.

Heart Disease in Women: Unappreciated Challenges, GPER as a New Target.

PubMed

Feldman, Ross D

2016-05-18

Heart disease in women remains underappreciated, underdiagnosed and undertreated. Further, although we are starting to understand some of the social and behavioral determinants for this, the biological basis for the increased rate of rise in atherosclerosis risk in women after menopause remains very poorly understand. In this review we will outline the scope of the clinical issues related to heart disease in women, the emerging findings regarding the biological basis underlying the increased prevalence of atherosclerotic risk factors in postmenopausal women (vs. men) and the role of the G protein-coupled estrogen receptor (GPER) and its genetic regulation as a determinant of these sex-specific risks. GPER is a recently appreciated GPCR that mediates the rapid effects of estrogen and aldosterone. Recent studies have identified that GPER activation regulates both blood pressure. We have shown that regulation of GPER function via expression of a hypofunctional GPER genetic variant is an important determinant of blood pressure and risk of hypertension in women. Further, our most recent studies have identified that GPER activation is an important regulator of low density lipoprotein (LDL) receptor metabolism and that expression of the hypofunctional GPER genetic variant is an important contributor to the development of hypercholesterolemia in women. GPER appears to be an important determinant of the two major risk factors for coronary artery disease-blood pressure and LDL cholesterol. Further, the importance of this mechanism appears to be greater in women. Thus, the appreciation of the role of GPER function as a determinant of the progression of atherosclerotic disease may be important both in our understanding of cardiometabolic function but also in opening the way to greater appreciation of the sex-specific regulation of atherosclerotic risk factors.

The halogenated metabolism of brown algae (Phaeophyta), its biological importance and its environmental significance.

PubMed

La Barre, Stéphane; Potin, Philippe; Leblanc, Catherine; Delage, Ludovic

2010-03-31

Brown algae represent a major component of littoral and sublittoral zones in temperate and subtropical ecosystems. An essential adaptive feature of this independent eukaryotic lineage is the ability to couple oxidative reactions resulting from exposure to sunlight and air with the halogenations of various substrates, thereby addressing various biotic and abiotic stresses i.e., defense against predators, tissue repair, holdfast adhesion, and protection against reactive species generated by oxidative processes. Whereas marine organisms mainly make use of bromine to increase the biological activity of secondary metabolites, some orders of brown algae such as Laminariales have also developed a striking capability to accumulate and to use iodine in physiological adaptations to stress. We review selected aspects of the halogenated metabolism of macrophytic brown algae in the light of the most recent results, which point toward novel functions for iodide accumulation in kelps and the importance of bromination in cell wall modifications and adhesion properties of brown algal propagules. The importance of halogen speciation processes ranges from microbiology to biogeochemistry, through enzymology, cellular biology and ecotoxicology.

The Halogenated Metabolism of Brown Algae (Phaeophyta), Its Biological Importance and Its Environmental Significance

PubMed Central

La Barre, Stéphane; Potin, Philippe; Leblanc, Catherine; Delage, Ludovic

2010-01-01

Brown algae represent a major component of littoral and sublittoral zones in temperate and subtropical ecosystems. An essential adaptive feature of this independent eukaryotic lineage is the ability to couple oxidative reactions resulting from exposure to sunlight and air with the halogenations of various substrates, thereby addressing various biotic and abiotic stresses i.e., defense against predators, tissue repair, holdfast adhesion, and protection against reactive species generated by oxidative processes. Whereas marine organisms mainly make use of bromine to increase the biological activity of secondary metabolites, some orders of brown algae such as Laminariales have also developed a striking capability to accumulate and to use iodine in physiological adaptations to stress. We review selected aspects of the halogenated metabolism of macrophytic brown algae in the light of the most recent results, which point toward novel functions for iodide accumulation in kelps and the importance of bromination in cell wall modifications and adhesion properties of brown algal propagules. The importance of halogen speciation processes ranges from microbiology to biogeochemistry, through enzymology, cellular biology and ecotoxicology. PMID:20479964

GPER (GPR30): A Nongenomic Receptor (GPCR) for Steroid Hormones with Implications for Cardiovascular Disease and Cancer.

PubMed

Feldman, Ross D; Limbird, Lee E

2017-01-06

Although the rapid effects of steroids, such as estrogen and aldosterone, were postulated originally to be nongenomic, it is now appreciated that activation of such signaling pathways via a steroid-acting G protein-coupled receptor, the G protein estrogen receptor (GPER), has important transcription-dependent outcomes in the regulation of cell growth and programmed cell death secondary to GPER-regulated second-messenger pathways. GPER is expressed ubiquitously and has diverse biological effects, including regulation of endocrine, immune, neuronal, and cardiovascular functions. Perhaps the most biologically important consequences of GPER activation are the regulation of cell growth, migration, and apoptotic cell death. These cell growth regulatory effects, important in cancer biology, are also relevant in the regulation of cardiac and vascular hypertrophy and in the response to ischemia. This review provides a summary of relevant findings of the impact of GPER regulation by either estradiol or aldosterone in in vitro model systems and extends those findings to in vivo studies of direct clinical relevance for development of GPER-directed agents for treatment of cancer and cardiovascular diseases associated with cellular proliferation.

Preclinical magnetic resonance imaging and systems biology in cancer research: current applications and challenges.

PubMed

Albanese, Chris; Rodriguez, Olga C; VanMeter, John; Fricke, Stanley T; Rood, Brian R; Lee, YiChien; Wang, Sean S; Madhavan, Subha; Gusev, Yuriy; Petricoin, Emanuel F; Wang, Yue

2013-02-01

Biologically accurate mouse models of human cancer have become important tools for the study of human disease. The anatomical location of various target organs, such as brain, pancreas, and prostate, makes determination of disease status difficult. Imaging modalities, such as magnetic resonance imaging, can greatly enhance diagnosis, and longitudinal imaging of tumor progression is an important source of experimental data. Even in models where the tumors arise in areas that permit visual determination of tumorigenesis, longitudinal anatomical and functional imaging can enhance the scope of studies by facilitating the assessment of biological alterations, (such as changes in angiogenesis, metabolism, cellular invasion) as well as tissue perfusion and diffusion. One of the challenges in preclinical imaging is the development of infrastructural platforms required for integrating in vivo imaging and therapeutic response data with ex vivo pathological and molecular data using a more systems-based multiscale modeling approach. Further challenges exist in integrating these data for computational modeling to better understand the pathobiology of cancer and to better affect its cure. We review the current applications of preclinical imaging and discuss the implications of applying functional imaging to visualize cancer progression and treatment. Finally, we provide new data from an ongoing preclinical drug study demonstrating how multiscale modeling can lead to a more comprehensive understanding of cancer biology and therapy. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Neuronal Organization of Deep Brain Opsin Photoreceptors in Adult Teleosts

PubMed Central

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

2016-01-01

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

The first Seriatum study of growth by R. E. Scammon.

PubMed

Miller, Elizabeth M

2018-03-01

Richard E. Scammon's article, "The First Seriatim Study of Human Growth," provided one of the best-known visuals in the field of human biology. Scammon resurrected longitudinal height data of one child from Buffon's Histoire Naturelle, converted them to metric, and plotted these measurements as a function of age. The result was the first graph of one individual's growth curve from birth to 18 years of age. This image was subsequently reproduced in numerous texts on human growth and biology. Published in 1927, Scammon's article provides a snapshot of the state of growth research at the time and gives a (literal) picture of the future of human biology. The graph of the growth of one child symbolizes the importance of process and variation in biological anthropology. © 2018 Wiley Periodicals, Inc.

Plasma membrane lipid–protein interactions affect signaling processes in sterol-biosynthesis mutants in Arabidopsis thaliana

PubMed Central

Zauber, Henrik; Burgos, Asdrubal; Garapati, Prashanth; Schulze, Waltraud X.

2014-01-01

The plasma membrane is an important organelle providing structure, signaling and transport as major biological functions. Being composed of lipids and proteins with different physicochemical properties, the biological functions of membranes depend on specific protein–protein and protein–lipid interactions. Interactions of proteins with their specific sterol and lipid environment were shown to be important factors for protein recruitment into sub-compartmental structures of the plasma membrane. System-wide implications of altered endogenous sterol levels for membrane functions in living cells were not studied in higher plant cells. In particular, little is known how alterations in membrane sterol composition affect protein and lipid organization and interaction within membranes. Here, we conducted a comparative analysis of the plasma membrane protein and lipid composition in Arabidopsis sterol-biosynthesis mutants smt1 and ugt80A2;B1. smt1 shows general alterations in sterol composition while ugt80A2;B1 is significantly impaired in sterol glycosylation. By systematically analyzing different cellular fractions and combining proteomic with lipidomic data we were able to reveal contrasting alterations in lipid–protein interactions in both mutants, with resulting differential changes in plasma membrane signaling status. PMID:24672530

Fetal Programming of Body Composition, Obesity, and Metabolic Function: The Role of Intrauterine Stress and Stress Biology

PubMed Central

Entringer, Sonja; Buss, Claudia; Swanson, James M.; Cooper, Dan M.; Wing, Deborah A.; Waffarn, Feizal; Wadhwa, Pathik D.

2012-01-01

Epidemiological, clinical, physiological, cellular, and molecular evidence suggests that the origins of obesity and metabolic dysfunction can be traced back to intrauterine life and supports an important role for maternal nutrition prior to and during gestation in fetal programming. The elucidation of underlying mechanisms is an area of interest and intense investigation. In this perspectives paper we propose that in addition to maternal nutrition-related processes it may be important to concurrently consider the potential role of intrauterine stress and stress biology. We frame our arguments in the larger context of an evolutionary-developmental perspective that supports roles for both nutrition and stress as key environmental conditions driving natural selection and developmental plasticity. We suggest that intrauterine stress exposure may interact with the nutritional milieu, and that stress biology may represent an underlying mechanism mediating the effects of diverse intrauterine perturbations, including but not limited to maternal nutritional insults (undernutrition and overnutrition), on brain and peripheral targets of programming of body composition, energy balance homeostasis, and metabolic function. We discuss putative maternal-placental-fetal endocrine and immune/inflammatory candidate mechanisms that may underlie the long-term effects of intrauterine stress. We conclude with a commentary of the implications for future research and clinical practice. PMID:22655178

Extracellular vesicles: their role in cancer biology and epithelial-mesenchymal transition.

PubMed

Gopal, Shashi K; Greening, David W; Rai, Alin; Chen, Maoshan; Xu, Rong; Shafiq, Adnan; Mathias, Rommel A; Zhu, Hong-Jian; Simpson, Richard J

2017-01-01

Cell-cell communication is critical across an assortment of physiological and pathological processes. Extracellular vesicles (EVs) represent an integral facet of intercellular communication largely through the transfer of functional cargo such as proteins, messenger RNAs (mRNAs), microRNA (miRNAs), DNAs and lipids. EVs, especially exosomes and shed microvesicles, represent an important delivery medium in the tumour micro-environment through the reciprocal dissemination of signals between cancer and resident stromal cells to facilitate tumorigenesis and metastasis. An important step of the metastatic cascade is the reprogramming of cancer cells from an epithelial to mesenchymal phenotype (epithelial-mesenchymal transition, EMT), which is associated with increased aggressiveness, invasiveness and metastatic potential. There is now increasing evidence demonstrating that EVs released by cells undergoing EMT are reprogrammed (protein and RNA content) during this process. This review summarises current knowledge of EV-mediated functional transfer of proteins and RNA species (mRNA, miRNA, long non-coding RNA) between cells in cancer biology and the EMT process. An in-depth understanding of EVs associated with EMT, with emphasis on molecular composition (proteins and RNA species), will provide fundamental insights into cancer biology. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Predicting Amyloidogenic Proteins in the Proteomes of Plants.

PubMed

Antonets, Kirill S; Nizhnikov, Anton A

2017-10-16

Amyloids are protein fibrils with characteristic spatial structure. Though amyloids were long perceived to be pathogens that cause dozens of incurable pathologies in humans and mammals, it is currently clear that amyloids also represent a functionally important form of protein structure implicated in a variety of biological processes in organisms ranging from archaea and bacteria to fungi and animals. Despite their social significance, plants remain the most poorly studied group of organisms in the field of amyloid biology. To date, amyloid properties have only been demonstrated in vitro or in heterologous systems for a small number of plant proteins. Here, for the first time, we performed a comprehensive analysis of the distribution of potentially amyloidogenic proteins in the proteomes of approximately 70 species of land plants using the Waltz and SARP (Sequence Analysis based on the Ranking of Probabilities) bioinformatic algorithms. We analyzed more than 2.9 million protein sequences and found that potentially amyloidogenic proteins are abundant in plant proteomes. We found that such proteins are overrepresented among membrane as well as DNA- and RNA-binding proteins of plants. Moreover, seed storage and defense proteins of most plant species are rich in amyloidogenic regions. Taken together, our data demonstrate the diversity of potentially amyloidogenic proteins in plant proteomes and suggest biological processes where formation of amyloids might be functionally important.

Protein-protein interactions in the regulation of WRKY transcription factors.

PubMed

Chi, Yingjun; Yang, Yan; Zhou, Yuan; Zhou, Jie; Fan, Baofang; Yu, Jing-Quan; Chen, Zhixiang

2013-03-01

It has been almost 20 years since the first report of a WRKY transcription factor, SPF1, from sweet potato. Great progress has been made since then in establishing the diverse biological roles of WRKY transcription factors in plant growth, development, and responses to biotic and abiotic stress. Despite the functional diversity, almost all analyzed WRKY proteins recognize the TTGACC/T W-box sequences and, therefore, mechanisms other than mere recognition of the core W-box promoter elements are necessary to achieve the regulatory specificity of WRKY transcription factors. Research over the past several years has revealed that WRKY transcription factors physically interact with a wide range of proteins with roles in signaling, transcription, and chromatin remodeling. Studies of WRKY-interacting proteins have provided important insights into the regulation and mode of action of members of the important family of transcription factors. It has also emerged that the slightly varied WRKY domains and other protein motifs conserved within each of the seven WRKY subfamilies participate in protein-protein interactions and mediate complex functional interactions between WRKY proteins and between WRKY and other regulatory proteins in the modulation of important biological processes. In this review, we summarize studies of protein-protein interactions for WRKY transcription factors and discuss how the interacting partners contribute, at different levels, to the establishment of the complex regulatory and functional network of WRKY transcription factors.

Polymer-induced compression of biological hydrogels

NASA Astrophysics Data System (ADS)

Datta, Sujit; Preska Steinberg, Asher; Ismagilov, Rustem

Hydrogels - such as mucus, blood clots, and the extracellular matrix - provide critical functions in biological systems. However, little is known about how their structure is influenced by many of the polymeric materials they come into contact with regularly. Here, we focus on one critically important biological hydrogel: colonic mucus. While several biological processes are thought to potentially regulate the mucus hydrogel structure, the polymeric composition of the gut environment has been ignored. We use Flory-Huggins solution theory to characterize polymer-mucus interactions. We find that gut polymers, including those small enough to penetrate the mucus hydrogel, can in fact alter mucus structure, changing its equilibrium degree of swelling and forcing it to compress. The extent of compression increases with increasing polymer concentration and size. We use experiments on mice to verify these predictions with common dietary and therapeutic gut polymers. Our results provide a foundation for investigating similar, previously overlooked, polymer-induced effects in other biological hydrogels.

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

PubMed

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

2013-12-01

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

Eduard Strasburger (1844-1912): founder of modern plant cell biology.

PubMed

Volkmann, Dieter; Baluška, František; Menzel, Diedrik

2012-10-01

Eduard Strasburger, director of the Botany Institute and the Botanical Garden at the University of Bonn from 1881 to 1912, was one of the most admirable scientists in the field of plant biology, not just as the founder of modern plant cell biology but in addition as an excellent teacher who strongly believed in "education through science." He contributed to plant cell biology by discovering the discrete stages of karyokinesis and cytokinesis in algae and higher plants, describing cytoplasmic streaming in different systems, and reporting on the growth of the pollen tube into the embryo sac and guidance of the tube by synergides. Strasburger raised many problems which are hot spots in recent plant cell biology, e.g., structure and function of the plasmodesmata in relation to phloem loading (Strasburger cells) and signaling, mechanisms of cell plate formation, vesicle trafficking as a basis for most important developmental processes, and signaling related to fertilization.

Functional Diversity of the Schistosoma mansoni Tyrosine Kinases

PubMed Central

Avelar, Lívia G. A.; Nahum, Laila A.; Andrade, Luiza F.; Oliveira, Guilherme

2011-01-01

Schistosoma mansoni, one of the causative agents of schistosomiasis, has a complex life cycle infecting over 200 million people worldwide. Such a successful and prolific parasite life cycle has been shown to be dependent on the adaptive interaction between the parasite and hosts. Tyrosine kinases (TKs) play a key role in signaling pathways as demonstrated by a large body of experimental work in eukaryotes. Furthermore, comparative genomics have allowed the identification of TK homologs and provided insights into the functional role of TKs in several biological systems. Finally, TK structural biology has provided a rational basis for obtaining selective inhibitors directed to the treatment of human diseases. This paper covers the important aspects of the phospho-tyrosine signaling network in S. mansoni, Caenorhabditis elegans, and humans, the main process of functional diversification of TKs, that is, protein-domain shuffling, and also discusses TKs as targets for the development of new anti-schistosome drugs. PMID:21776387

STAT6: its role in interleukin 4-mediated biological functions.

PubMed

Takeda, K; Kishimoto, T; Akira, S

1997-05-01

Interleukin (IL) 4 is known to be a cytokine which plays a central role in the regulation of immune response. Studies on cytokine signal transduction have clarified the mechanism by which IL4 exerts its functions. Two cytoplasmic proteins, signal transducer and activator of transcription (STAT) 6 and IL4-induced phosphotyrosine substrate/insulin receptor substrate 2 (4PS/IRS2), are activated in IL4 signal transduction. Recent studies from STAT6-deficient mice have revealed the essential role of STAT6 in IL4-mediated biological actions. In addition, STAT6 has also been demonstrated to be important for the functions mediated by IL13, which is related to IL4. IL4 and IL13 have been shown to induce the production of IgE, which is a major mediator in an allergic response. These findings indicate that STAT6 activation is involved in IL4- and IL13-mediated disorders such as allergy.

Development of a novel monoclonal antibody to human inducible co-stimulator ligand (ICOSL): Biological characteristics and application for enzyme-linked immunosorbent assay.

PubMed

Hu, Xiaohan; Wu, Jian; An, Jingnan; Hu, Yumin; Shen, Yu; Liu, Cuiping; Zhang, Xueguang

2016-07-01

ICOSL (B7-H2, CD275), a co-stimulatory molecule of the B7 superfamily, functions as a positive signal in immune response. To investigate whether ICOSL could be released into sera and the possible biological function of soluble ICOS (sICOSL), we generated and characterized a functional anti-human ICOSL monoclonal antibody (mAb), 20B10, and developed a novel enzyme-linked immunosorbent assay (ELISA) based on two anti-human ICOSL antibodies with different epitope specificities. Using the ELISA system, we found that sICOSL in the serum of healthy donors increases in an age-dependent manner and that the matrix metalloproteinase inhibitor (MMPI) could suppress sICOSL production. Together, these data demonstrate that the existence of circulating sICOSL in human serum might play an important role in immunoregulation. Copyright © 2016. Published by Elsevier B.V.

An Update on Cellular MicroRNA Expression in Human Papillomavirus-Associated Head and Neck Squamous Cell Carcinoma.

PubMed

Emmett, Sarah; Whiteman, David C; Panizza, Benedict J; Antonsson, Annika

2018-06-19

Squamous cell carcinoma of mucosal sites in the head and neck (HNSCC) is the sixth most common cause of cancer worldwide, and despite advances in conventional management, it still has significant morbidity and mortality associated with both diagnosis and treatment. Advances in our understanding of the biological mechanisms underlying this disease have demonstrated a significant difference between human papillomavirus (HPV)-associated, HPV and tobacco associated, and HPV-negative disease. It remains important to further elucidate the biologic and genetic differences between HPV-associated and tobacco-associated disease, with the aim of earlier diagnosis through screening, and advances in management including the development of novel therapeutic agents. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression, and have effects on almost every cellular function, and have potentially important applications to diagnosis, management and prognosis in HNSCC. Establishing a cellular miRNA expression profile for HPV-associated disease may therefore have important implications for the screening and treatment of this disease. This review summarises the current findings regarding miRNA expression in mucosal HNSCC, and focuses particularly on miRNA expression in HPV-associated tumours. © 2018 S. Karger AG, Basel.

The Role of Protein Loops and Linkers in Conformational Dynamics and Allostery.

PubMed

Papaleo, Elena; Saladino, Giorgio; Lambrughi, Matteo; Lindorff-Larsen, Kresten; Gervasio, Francesco Luigi; Nussinov, Ruth

2016-06-08

Proteins are dynamic entities that undergo a plethora of conformational changes that may take place on a wide range of time scales. These changes can be as small as the rotation of one or a few side-chain dihedral angles or involve concerted motions in larger portions of the three-dimensional structure; both kinds of motions can be important for biological function and allostery. It is becoming increasingly evident that "connector regions" are important components of the dynamic personality of protein structures. These regions may be either disordered loops, i.e., poorly structured regions connecting secondary structural elements, or linkers that connect entire protein domains. Experimental and computational studies have, however, revealed that these regions are not mere connectors, and their role in allostery and conformational changes has been emerging in the last few decades. Here we provide a detailed overview of the structural properties and classification of loops and linkers, as well as a discussion of the main computational methods employed to investigate their function and dynamical properties. We also describe their importance for protein dynamics and allostery using as examples key proteins in cellular biology and human diseases such as kinases, ubiquitinating enzymes, and transcription factors.

Are biological effects of desert shrubs more important than physical effects on soil microorganisms?

PubMed

Berg, Naama; Steinberger, Yosef

2010-01-01

Vegetation cover plays a major role in providing organic matter and in acting as a physical barrier, with both together contributing to the formation of "fertile islands," which play an active role in prolonging biological activity in desert ecosystems. By undertaking this study, a longterm research, we designed an experiment to separate the two components-the physical and biotic parts of the perennial plants-and to identify the factor that contributes the most to the ecosystem. The study site was located in the northern Negev Desert, Israel, where 50 Hammada scoparia shrubs and 50 artificial plants were randomly marked. Soil samples were collected monthly over 3 years of research at three locations: under the canopy of H. scoparia shrubs, in the vicinity of the artificial plants, and between the shrubs (control). The contribution to microbial activity was measured by evaluation of the microbial community functions in soil. The functional aspects of the microbial community that were measured were CO2 evolution, microbial biomass, microbial functional diversity, and the physiological profile of the community. The results of this study are presented in two ways: (1) according to the three locations/treatments; and (2) according to the phenological situation of the vegetation (annual and perennial plants) in the research field: the growing phase, the drying process, and the absence of annual plants. The only parameters that were found to affect microbial activity were the contribution of the organic matter of perennial shrubs and the growth of vegetation (annual and perennial) during the growing seasons. The physical component was found to have no effect on soil microbial functional diversity, which elucidates the important contribution of the desert shrub in enhancing biological multiplicity and activity.

Modularity and evolutionary constraints in a baculovirus gene regulatory network

PubMed Central

2013-01-01

Background The structure of regulatory networks remains an open question in our understanding of complex biological systems. Interactions during complete viral life cycles present unique opportunities to understand how host-parasite network take shape and behave. The Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) is a large double-stranded DNA virus, whose genome may encode for 152 open reading frames (ORFs). Here we present the analysis of the ordered cascade of the AgMNPV gene expression. Results We observed an earlier onset of the expression than previously reported for other baculoviruses, especially for genes involved in DNA replication. Most ORFs were expressed at higher levels in a more permissive host cell line. Genes with more than one copy in the genome had distinct expression profiles, which could indicate the acquisition of new functionalities. The transcription gene regulatory network (GRN) for 149 ORFs had a modular topology comprising five communities of highly interconnected nodes that separated key genes that are functionally related on different communities, possibly maximizing redundancy and GRN robustness by compartmentalization of important functions. Core conserved functions showed expression synchronicity, distinct GRN features and significantly less genetic diversity, consistent with evolutionary constraints imposed in key elements of biological systems. This reduced genetic diversity also had a positive correlation with the importance of the gene in our estimated GRN, supporting a relationship between phylogenetic data of baculovirus genes and network features inferred from expression data. We also observed that gene arrangement in overlapping transcripts was conserved among related baculoviruses, suggesting a principle of genome organization. Conclusions Albeit with a reduced number of nodes (149), the AgMNPV GRN had a topology and key characteristics similar to those observed in complex cellular organisms, which indicates that modularity may be a general feature of biological gene regulatory networks. PMID:24006890

Structure, Biology, and Therapeutic Application of Toxin-Antitoxin Systems in Pathogenic Bacteria.

PubMed

Lee, Ki-Young; Lee, Bong-Jin

2016-10-22

Bacterial toxin-antitoxin (TA) systems have received increasing attention for their diverse identities, structures, and functional implications in cell cycle arrest and survival against environmental stresses such as nutrient deficiency, antibiotic treatments, and immune system attacks. In this review, we describe the biological functions and the auto-regulatory mechanisms of six different types of TA systems, among which the type II TA system has been most extensively studied. The functions of type II toxins include mRNA/tRNA cleavage, gyrase/ribosome poison, and protein phosphorylation, which can be neutralized by their cognate antitoxins. We mainly explore the similar but divergent structures of type II TA proteins from 12 important pathogenic bacteria, including various aspects of protein-protein interactions. Accumulating knowledge about the structure-function correlation of TA systems from pathogenic bacteria has facilitated a novel strategy to develop antibiotic drugs that target specific pathogens. These molecules could increase the intrinsic activity of the toxin by artificially interfering with the intermolecular network of the TA systems.

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

PubMed

Papini, Christina; Royer, Catherine A

2018-02-01

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

All-atom molecular dynamics of the HBV capsid reveals insights into biological function and cryo-EM resolution limits

PubMed Central

Perilla, Juan R; Schlicksup, Christopher John; Venkatakrishnan, Balasubramanian; Zlotnick, Adam; Schulten, Klaus

2018-01-01

The hepatitis B virus capsid represents a promising therapeutic target. Experiments suggest the capsid must be flexible to function; however, capsid structure and dynamics have not been thoroughly characterized in the absence of icosahedral symmetry constraints. Here, all-atom molecular dynamics simulations are leveraged to investigate the capsid without symmetry bias, enabling study of capsid flexibility and its implications for biological function and cryo-EM resolution limits. Simulation results confirm flexibility and reveal a propensity for asymmetric distortion. The capsid’s influence on ionic species suggests a mechanism for modulating the display of cellular signals and implicates the capsid’s triangular pores as the location of signal exposure. A theoretical image reconstruction performed using simulated conformations indicates how capsid flexibility may limit the resolution of cryo-EM. Overall, the present work provides functional insight beyond what is accessible to experimental methods and raises important considerations regarding asymmetry in structural studies of icosahedral virus capsids. PMID:29708495

Constructive Approaches for Understanding the Origin of Self-Replication and Evolution.

PubMed

Ichihashi, Norikazu; Yomo, Tetsuya

2016-07-13

The mystery of the origin of life can be divided into two parts. The first part is the origin of biomolecules: under what physicochemical conditions did biomolecules such as amino acids, nucleotides, and their polymers arise? The second part of the mystery is the origin of life-specific functions such as the replication of genetic information, the reproduction of cellular structures, metabolism, and evolution. These functions require the coordination of many different kinds of biological molecules. A direct strategy to approach the second part of the mystery is the constructive approach, in which life-specific functions are recreated in a test tube from specific biological molecules. Using this approach, we are able to employ design principles to reproduce life-specific functions, and the knowledge gained through the reproduction process provides clues as to their origins. In this mini-review, we introduce recent insights gained using this approach, and propose important future directions for advancing our understanding of the origins of life.

Structure, Biology, and Therapeutic Application of Toxin–Antitoxin Systems in Pathogenic Bacteria

PubMed Central

Lee, Ki-Young; Lee, Bong-Jin

2016-01-01

Bacterial toxin–antitoxin (TA) systems have received increasing attention for their diverse identities, structures, and functional implications in cell cycle arrest and survival against environmental stresses such as nutrient deficiency, antibiotic treatments, and immune system attacks. In this review, we describe the biological functions and the auto-regulatory mechanisms of six different types of TA systems, among which the type II TA system has been most extensively studied. The functions of type II toxins include mRNA/tRNA cleavage, gyrase/ribosome poison, and protein phosphorylation, which can be neutralized by their cognate antitoxins. We mainly explore the similar but divergent structures of type II TA proteins from 12 important pathogenic bacteria, including various aspects of protein–protein interactions. Accumulating knowledge about the structure–function correlation of TA systems from pathogenic bacteria has facilitated a novel strategy to develop antibiotic drugs that target specific pathogens. These molecules could increase the intrinsic activity of the toxin by artificially interfering with the intermolecular network of the TA systems. PMID:27782085

Report of the matrix of biological knowledge workshop

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

Morowitz, H.J.; Smith, T.

1987-10-30

Current understanding of biology involves complex relationships rooted in enormous amounts of data. These data include entries from biochemistry, ecology, genetics, human and veterinary medicine, molecular structure studies, agriculture, embryology, systematics, and many other disciplines. The present wealth of biological data goes beyond past accumulations now include new understandings from molecular biology. Several important biological databases are currently being supported, and more are planned; however, major problems of interdatabase communication and management efficiency abound. Few scientists are currently capable of keeping up with this ever-increasing wealth of knowledge, let alone searching it efficiently for new or unsuspected links and importantmore » analogies. Yet this is what is required if the continued rapid generation of such data is to lead most effectively to the major conceptual, medical, and agricultural advances anticipated over the coming decades in the United States. The opportunity exists to combine the potential of modern computer science, database management, and artificial intelligence in a major effort to organize the vast wealth of biological and clinical data. The time is right because the amount of data is still manageable even in its current highly-fragmented form; important hardware and computer science tools have been greatly improved; and there have been recent fundamental advances in our comprehension of biology. This latter is particularly true at the molecular level where the information for nearly all higher structure and function is encoded. The organization of all biological experimental data coordinately within a structure incorporating our current understanding - the Matrix of Biological Knowledge - will provide the data and structure for the major advances foreseen in the years ahead.« less

Avian host defense peptides.

PubMed

Cuperus, Tryntsje; Coorens, Maarten; van Dijk, Albert; Haagsman, Henk P

2013-11-01

Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense of many organisms. It is becoming increasingly clear that in the animal kingdom the functions of HDPs are not confined to direct antimicrobial actions. Research in mammals has indicated that HDPs have many immunomodulatory functions and are also involved in other physiological processes ranging from development to wound healing. During the past five years our knowledge about avian HDPs has increased considerably. This review addresses our current knowledge on the evolution, regulation and biological functions of HDPs of birds. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical regulators of plant hormones and their applications in basic research and agriculture.

PubMed

Jiang, Kai; Asami, Tadao

2018-04-20

Plant hormones are small molecules that play versatile roles in regulating plant growth, development, and responses to the environment. Classic methodologies, including genetics, analytic chemistry, biochemistry, and molecular biology, have contributed to the progress in plant hormone studies. In addition, chemical regulators of plant hormone functions have been important in such studies. Today, synthetic chemicals, including plant growth regulators, are used to study and manipulate biological systems, collectively referred to as chemical biology. Here, we summarize the available chemical regulators and their contributions to plant hormone studies. We also pose questions that remain to be addressed in plant hormone studies and that might be solved with the help of chemical regulators.

Sensors and actuators inherent in biological species

NASA Astrophysics Data System (ADS)

Taya, Minoru; Stahlberg, Rainer; Li, Fanghong; Zhao, Ying Joyce

2007-04-01

This paper addresses examples of sensing and active mechanisms inherent in some biological species where both plants and animals cases are discussed: mechanosensors and actuators in Venus Fly Trap and cucumber tendrils, chemosensors in insects, two cases of interactions between different kingdoms, (i) cotton plant smart defense system and (ii) bird-of-paradise flower and hamming bird interaction. All these cases lead us to recognize how energy-efficient and flexible the biological sensors and actuators are. This review reveals the importance of integration of sensing and actuation functions into an autonomous system if we make biomimetic design of a set of new autonomous systems which can sense and actuate under a number of different stimuli and threats.

Joining Forces: Integrating Proteomics and Cross-linking with the Mass Spectrometry of Intact Complexes*

PubMed Central

Stengel, Florian; Aebersold, Ruedi; Robinson, Carol V.

2012-01-01

Protein assemblies are critical for cellular function and understanding their physical organization is the key aim of structural biology. However, applying conventional structural biology approaches is challenging for transient, dynamic, or polydisperse assemblies. There is therefore a growing demand for hybrid technologies that are able to complement classical structural biology methods and thereby broaden our arsenal for the study of these important complexes. Exciting new developments in the field of mass spectrometry and proteomics have added a new dimension to the study of protein-protein interactions and protein complex architecture. In this review, we focus on how complementary mass spectrometry-based techniques can greatly facilitate structural understanding of protein assemblies. PMID:22180098

Free-falling Crystals: Biological Macromolecular Crystal Growth Studies in Low Earth Orbit

NASA Technical Reports Server (NTRS)

Judge, Russell A.; Snell, E. H.; Pusey, M. L.; Whitaker, Ann F. (Technical Monitor)

2001-01-01

Spacecraft orbiting the earth experience a reduced acceleration environment due to being in a state of continuous free-fall. This state colloquially termed microgravity, has produced improved X-ray diffraction quality crystals of biological macromolecules. Improvements in X-ray diffraction resolution (detail) or signal to noise, provide greater detail in the three-dimensional molecular structure providing information about the molecule, how it works, how to improve its function or how to impede it. Greater molecular detail obtained by crystallization in microgravity, has important implications for structural biology. In this article we examine the theories behind macromolecule crystal quality improvement in microgravity using results obtained from studies with the model protein, chicken egg white lysozyme.

Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression.

PubMed

Willms, Eduard; Cabañas, Carlos; Mäger, Imre; Wood, Matthew J A; Vader, Pieter

2018-01-01

Cells release membrane enclosed nano-sized vesicles termed extracellular vesicles (EVs) that function as mediators of intercellular communication by transferring biological information between cells. Tumor-derived EVs have emerged as important mediators in cancer development and progression, mainly through transfer of their bioactive content which can include oncoproteins, oncogenes, chemokine receptors, as well as soluble factors, transcripts of proteins and miRNAs involved in angiogenesis or inflammation. This transfer has been shown to influence the metastatic behavior of primary tumors. Moreover, tumor-derived EVs have been shown to influence distant cellular niches, establishing favorable microenvironments that support growth of disseminated cancer cells upon their arrival at these pre-metastatic niches. It is generally accepted that cells release a number of major EV populations with distinct biophysical properties and biological functions. Exosomes, microvesicles, and apoptotic bodies are EV populations most widely studied and characterized. They are discriminated based primarily on their intracellular origin. However, increasing evidence suggests that even within these EV populations various subpopulations may exist. This heterogeneity introduces an extra level of complexity in the study of EV biology and function. For example, EV subpopulations could have unique roles in the intricate biological processes underlying cancer biology. Here, we discuss current knowledge regarding the role of subpopulations of EVs in cancer development and progression and highlight the relevance of EV heterogeneity. The position of tetraspanins and integrins therein will be highlighted. Since addressing EV heterogeneity has become essential for the EV field, current and novel techniques for isolating EV subpopulations will also be discussed. Further dissection of EV heterogeneity will advance our understanding of the critical roles of EVs in health and disease.

Reactions of the nervous system to magnetic fields

NASA Technical Reports Server (NTRS)

Kholodov, Y. A.

1974-01-01

This magnetobiological survey considers sensory, nervous, stress and genetic effects of magnetic fields on man and animals. It is shown that the nervous system plays an important role in the reactions of the organism to magnetic fields; the final biological effect is a function of the strength of the magnetic fields, the gradient, direction of the lines of force, duration and location of the action, and the functional status of the organism.

The impact of iron on the bleaching efficacy of hydrogen peroxide in liquid whey systems.

PubMed

Jervis, Suzanne M; Drake, MaryAnne

2013-02-01

Whey is a value-added product that is utilized in many food and beverage applications for its nutritional and functional properties. Whey and whey products are generally utilized in dried ingredient applications. One of the primary sources of whey is from colored Cheddar cheese manufacture that contains the pigment annatto resulting in a characteristic yellow colored Cheddar cheese. The colorant is also present in the liquid cheese whey and must be bleached so that it can be used in ingredient applications without imparting a color. Hydrogen peroxide and benzoyl peroxide are 2 commercially approved chemical bleaching agents for liquid whey. Concerns regarding bleaching efficacy, off-flavor development, and functionality changes have been previously reported for whey bleached with hydrogen peroxide and benzoyl peroxide. It is very important for the dairy industry to understand how bleaching can impact flavor and functionality of dried ingredients. Currently, the precise mechanisms of off-flavor development and functionality changes are not entirely understood. Iron reactions in a bleached liquid whey system may play a key role. Reactions between iron and hydrogen peroxide have been widely studied since the reaction between these 2 relatively stable species can cause great destruction in biological and chemical systems. The actual mechanism of the reaction of iron with hydrogen peroxide has been a controversy in the chemistry and biological community. The precise mechanism for a given reaction can vary greatly based upon the concentration of reactants, temperature, pH, and addition of biological material. In this review, some hypotheses for the mechanisms of iron reactions that may occur in fluid whey that may impact bleaching efficacy, off-flavor development, and changes in functionality are presented. Cheese whey is bleached to remove residual carotenoid cheese colorant. Concerns regarding bleaching efficacy, off-flavor development, and functionality changes have been reported for whey proteins bleached with hydrogen peroxide and benzoyl peroxide. It is very important for the dairy industry to understand how whey bleaching can impact flavor and functionality of dried ingredients. Proposed mechanisms of off-flavor development and functionality changes are discussed in this hypothesis paper. © 2013 Institute of Food Technologists®

SorghumFDB: sorghum functional genomics database with multidimensional network analysis.

PubMed

Tian, Tian; You, Qi; Zhang, Liwei; Yi, Xin; Yan, Hengyu; Xu, Wenying; Su, Zhen

2016-01-01

Sorghum (Sorghum bicolor [L.] Moench) has excellent agronomic traits and biological properties, such as heat and drought-tolerance. It is a C4 grass and potential bioenergy-producing plant, which makes it an important crop worldwide. With the sorghum genome sequence released, it is essential to establish a sorghum functional genomics data mining platform. We collected genomic data and some functional annotations to construct a sorghum functional genomics database (SorghumFDB). SorghumFDB integrated knowledge of sorghum gene family classifications (transcription regulators/factors, carbohydrate-active enzymes, protein kinases, ubiquitins, cytochrome P450, monolignol biosynthesis related enzymes, R-genes and organelle-genes), detailed gene annotations, miRNA and target gene information, orthologous pairs in the model plants Arabidopsis, rice and maize, gene loci conversions and a genome browser. We further constructed a dynamic network of multidimensional biological relationships, comprised of the co-expression data, protein-protein interactions and miRNA-target pairs. We took effective measures to combine the network, gene set enrichment and motif analyses to determine the key regulators that participate in related metabolic pathways, such as the lignin pathway, which is a major biological process in bioenergy-producing plants.Database URL: http://structuralbiology.cau.edu.cn/sorghum/index.html. © The Author(s) 2016. Published by Oxford University Press.

Emergent properties of interacting populations of spiking neurons.

PubMed

Cardanobile, Stefano; Rotter, Stefan

2011-01-01

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

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

NASA Astrophysics Data System (ADS)

Gao, Yingxin; Zhang, Chi

2015-03-01

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

Exploration of the Energy Landscape of Acetylcholinesterase by Molecular Dynamics Simulation.

NASA Astrophysics Data System (ADS)

McCammon, J. Andrew

2002-03-01

Proteins have rough energy landscapes. Often more states than just the ground state are occupied and have biological functions. It is essential to study these conformational substates and the dynamical transitions among them. Acetylcholinesterase (AChE) is an important enzyme that has biological functions including the termination of synaptic transmission signals. X-ray structures show that it has an active site that is accessible only via a long and narrow channel from its surface. Therefore the fact that acetylcholine and larger ligands can reach the active site is believed to reflect the protein's structural fluctuation. We carried out long molecular dynamics simulations to investigate the dynamics of AChE and its relation to biological function, and compared our results with experiments. The results reveal several "doors" that open intermittantly between the active site and the surface. Instead of having simple exponential decay correlation functions, the time series of these channels reveal complex, fractal gating between conformations. We also compared the AChE dynamics data with those from an AchE-fasciculin complex. (Fasciculin is a small protein that is a natural inhibitor of AChE.) The results show remarkable effects of the protein-protein interaction, including allosteric and dynamical inhibition by fasciculin besides direct steric blocking. More information and images can be found at http://mccammon.ucsd.edu

Sex and gender differences in substance use disorders.

PubMed

McHugh, R Kathryn; Votaw, Victoria R; Sugarman, Dawn E; Greenfield, Shelly F

2017-11-10

The gender gap in substance use disorders (SUDs), characterized by greater prevalence in men, is narrowing, highlighting the importance of understanding sex and gender differences in SUD etiology and maintenance. In this critical review, we provide an overview of sex/gender differences in the biology, epidemiology and treatment of SUDs. Biological sex differences are evident across an array of systems, including brain structure and function, endocrine function, and metabolic function. Gender (i.e., environmentally and socioculturally defined roles for men and women) also contributes to the initiation and course of substance use and SUDs. Adverse medical, psychiatric, and functional consequences associated with SUDs are often more severe in women. However, men and women do not substantively differ with respect to SUD treatment outcomes. Although several trends are beginning to emerge in the literature, findings on sex and gender differences in SUDs are complicated by the interacting contributions of biological and environmental factors. Future research is needed to further elucidate sex and gender differences, especially focusing on hormonal factors in SUD course and treatment outcomes; research translating findings between animal and human models; and gender differences in understudied populations, such as those with co-occurring psychiatric disorders and gender-specific populations, such as pregnant women. Copyright © 2017 Elsevier Ltd. All rights reserved.

Emergent Properties of Interacting Populations of Spiking Neurons

PubMed Central

Cardanobile, Stefano; Rotter, Stefan

2011-01-01

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

Synthetic biology of cyanobacteria: unique challenges and opportunities

PubMed Central

Berla, Bertram M.; Saha, Rajib; Immethun, Cheryl M.; Maranas, Costas D.; Moon, Tae Seok; Pakrasi, Himadri B.

2013-01-01

Photosynthetic organisms, and especially cyanobacteria, hold great promise as sources of renewably-produced fuels, bulk and specialty chemicals, and nutritional products. Synthetic biology tools can help unlock cyanobacteria's potential for these functions, but unfortunately tool development for these organisms has lagged behind that for S. cerevisiae and E. coli. While these organisms may in many cases be more difficult to work with as “chassis” strains for synthetic biology than certain heterotrophs, the unique advantages of autotrophs in biotechnology applications as well as the scientific importance of improved understanding of photosynthesis warrant the development of these systems into something akin to a “green E. coli.” In this review, we highlight unique challenges and opportunities for development of synthetic biology approaches in cyanobacteria. We review classical and recently developed methods for constructing targeted mutants in various cyanobacterial strains, and offer perspective on what genetic tools might most greatly expand the ability to engineer new functions in such strains. Similarly, we review what genetic parts are most needed for the development of cyanobacterial synthetic biology. Finally, we highlight recent methods to construct genome-scale models of cyanobacterial metabolism and to use those models to measure properties of autotrophic metabolism. Throughout this paper, we discuss some of the unique challenges of a diurnal, autotrophic lifestyle along with how the development of synthetic biology and biotechnology in cyanobacteria must fit within those constraints. PMID:24009604

Research on some functions of Azolla in CELSS system

NASA Astrophysics Data System (ADS)

Liu, Xiaofeng; Min, Chen; Xia-shi, Liu; Chungchu, Liu

This article detailed the possibility of using Azolla in CELSS system, the characters of Azolla; the experiments on using Azolla as O 2-releasing plant to provide O 2 for human in airtight chamber; using Azolla as an important biological part for urine solution purification was also introduced.

Ecosystem management and its role in linking science, policy, and management

Treesearch

Matthew Skroch

2005-01-01

The scientific community has recently emphasized the importance of ecological process, structure, and scale in the maintenance of biological diversity. Humans have affected most natural landscapes, and many naturally occurring processes, structures, and species may not rebound to naturally sustaining function without intervention. Ecosystem management relies on science...

Housing is positively associated with invasive exotic plant species richness in New England, USA

Treesearch

Gregorio I. Gavier-Pizarro; Volker C. Radeloff; Susan I. Stewart; Cynthia D. Huebner; Nicholas S. Keuler

2010-01-01

Understanding the factors related to invasive exotic species distributions at broad spatial scales has important theoretical and management implications, because biological invasions are detrimental to many ecosystem functions and processes. Housing development facilitates invasions by disturbing land cover, introducing nonnative landscaping plants, and facilitating...

Postdoctoral Fellows | Center for Cancer Research

Cancer.gov

The Laboratory of Tumor Immunology and Biology (LTIB) functions as a multidisciplinary and interdisciplinary translational research programmatic effort with the goal of developing novel immunotherapies for cancer. The LTIB strategic plan focuses on the development of novel immunotherapeutics for human cancer, not only as monotherapies, but more importantly, in combination with

BUILDING REALISTIC BIOLOGICALLY-BASED PHARMACOKINETIC MODELS FOR PREDICTING SUSCEPTIBILITY IN THE AGED POPULATIONS

EPA Science Inventory

Detoxification and elimination of xenobiotics is a major function of the liver and is important in maintaining the metabolic homeostasis of the organism. The degree to which aging affects hepatic metabolism is not known. The expression of XMEs, in part, determines the fate of the...

Effect of supplemental taurine on juvenile channel catfish Ictalurus punctatus growth performance

USDA-ARS?s Scientific Manuscript database

Taurine is a beta-amino sulfur amino acid found in most animal tissues that has many important biological functions including bile salt conjugation, cellular osmoregulation, neuromodulation, calcium signaling. The benefits of supplementing diets with taurine are just beginning to be realized in a n...

Synthesis, surface modification and biological imaging of aggregation-induced emission (AIE) dye doped silica nanoparticles

NASA Astrophysics Data System (ADS)

Mao, Liucheng; Liu, Meiying; Xu, Dazhuang; Wan, Qing; Huang, Qiang; Jiang, Ruming; Shi, Yingge; Deng, Fengjie; Zhang, Xiaoyong; Wei, Yen

2017-05-01

Fluorescent silica nanoparticles (FSNPs) have been extensively investigated for various biomedical applications in recently years. However, the aggregation of organic dyes in silica nanoparticles also leads the significant fluorescence quenching owing to the aggregation caused quenching effects of organic dyes. Herein, we developed a rather facile strategy to fabricate FSNPs with desirable fluorescent properties through non-covalent incorporation of fluorophores with aggregation-induced emission (AIE) feature into silica nanoparticles, which were subsequently modified with functional polymers. The resultant FSNPs polymer nanocomposites (named as FSNPs-poly(IA-co-PEGMA)) exhibited uniform spherical morphology, high water dispersiity, and bright red fluorescence. Cytotoxicity results indicate that FSNPs-poly(IA-co-PEGMA) possess excellent biocompatibility. Cell uptake behavior suggests FSNPs-poly(IA-co-PEGMA) are of great potential for biological imaging applications. Taken together, we have reported a facile method for the fabrication of FSNPs through non-covalent encapsulation using an AIE-active dye. These FSNPs can be further functionalized with functional polymers through ring-opening reaction and the resultant FSNPs-poly(IA-co-PEGMA) showed great potential for biological imaging. More importantly, we believe that many other functional components could also be integrated into these FSNPs through the facile ring-opening reaction. Therefore, this method should be a facile and general tool for fabrication of polymer functionalized AIE-active FSNPs.

Design and construction of a first-generation high-throughput integrated robotic molecular biology platform for bioenergy applications.

PubMed

Hughes, Stephen R; Butt, Tauseef R; Bartolett, Scott; Riedmuller, Steven B; Farrelly, Philip

2011-08-01

The molecular biological techniques for plasmid-based assembly and cloning of gene open reading frames are essential for elucidating the function of the proteins encoded by the genes. High-throughput integrated robotic molecular biology platforms that have the capacity to rapidly clone and express heterologous gene open reading frames in bacteria and yeast and to screen large numbers of expressed proteins for optimized function are an important technology for improving microbial strains for biofuel production. The process involves the production of full-length complementary DNA libraries as a source of plasmid-based clones to express the desired proteins in active form for determination of their functions. Proteins that were identified by high-throughput screening as having desired characteristics are overexpressed in microbes to enable them to perform functions that will allow more cost-effective and sustainable production of biofuels. Because the plasmid libraries are composed of several thousand unique genes, automation of the process is essential. This review describes the design and implementation of an automated integrated programmable robotic workcell capable of producing complementary DNA libraries, colony picking, isolating plasmid DNA, transforming yeast and bacteria, expressing protein, and performing appropriate functional assays. These operations will allow tailoring microbial strains to use renewable feedstocks for production of biofuels, bioderived chemicals, fertilizers, and other coproducts for profitable and sustainable biorefineries. Published by Elsevier Inc.

Bioinspired surface functionalization of metallic biomaterials.

PubMed

Su, Yingchao; Luo, Cheng; Zhang, Zhihui; Hermawan, Hendra; Zhu, Donghui; Huang, Jubin; Liang, Yunhong; Li, Guangyu; Ren, Luquan

2018-01-01

Metallic biomaterials are widely used for clinical applications because of their excellent mechanical properties and good durability. In order to provide essential biofunctionalities, surface functionalization is of particular interest and requirement in the development of high-performance metallic implants. Inspired by the functional surface of natural biological systems, many new designs and conceptions have recently emerged to create multifunctional surfaces with great potential for biomedical applications. This review firstly introduces the metallic biomaterials, important surface properties, and then elaborates some strategies on achieving the bioinspired surface functionalization for metallic biomaterials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical Probes of Histone Lysine Methyltransferases

PubMed Central

2015-01-01

Growing evidence suggests that histone methyltransferases (HMTs, also known as protein methyltransferases (PMTs)) play an important role in diverse biological processes and human diseases by regulating gene expression and the chromatin state. Therefore, HMTs have been increasingly recognized by the biomedical community as a class of potential therapeutic targets. High quality chemical probes of HMTs, as tools for deciphering their physiological functions and roles in human diseases and testing therapeutic hypotheses, are critical for advancing this promising field. In this review, we focus on the discovery, characterization, and biological applications of chemical probes for HMTs. PMID:25423077

Regarding on the prototype solutions for the nonlinear fractional-order biological population model

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

Baskonus, Haci Mehmet, E-mail: hmbaskonus@gmail.com; Bulut, Hasan

2016-06-08

In this study, we have submitted to literature a method newly extended which is called as Improved Bernoulli sub-equation function method based on the Bernoulli Sub-ODE method. The proposed analytical scheme has been expressed with steps. We have obtained some new analytical solutions to the nonlinear fractional-order biological population model by using this technique. Two and three dimensional surfaces of analytical solutions have been drawn by wolfram Mathematica 9. Finally, a conclusion has been submitted by mentioning important acquisitions founded in this study.

Functionalized Nanodiamonds for Biological and Medical Applications.

PubMed

Lai, Lin; Barnard, Amanda S

2015-02-01

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

The structural biology of phenazine biosynthesis

PubMed Central

Blankenfeldt, Wulf; Parsons, James F.

2014-01-01

The phenazines are a class of over 150 nitrogen-containing aromatic compounds of bacterial and archeal origin. Their redox properties not only explain their activity as broad-specificity antibiotics and virulence factors but also enable them to function as respiratory pigments, thus extending their importance to the primary metabolism of phenazine-producing species. Despite their discovery in the mid-19th century, the molecular mechanisms behind their biosynthesis have only been unraveled in the last decade. Here, we review the contribution of structural biology that has led to our current understanding of phenazine biosynthesis. PMID:25215885

[On the importance of the steam trap to the efficient sterilization of solutions in stored blood bottles by saturated steam under pressure (author's transl)].

PubMed

Schreiber, M; Göbel, M

1979-01-01

Biological tests with soil samples were performed to fix the sterilization time for a new steam sterilizer. These tests yielded repeatedly positive spore findings despite modifications of the conditions of sterilization. Having excluded a series of possible sources of trouble, the authors stated that the quality of the steam was the assignable cause. After restoration of the functionality of the steam traps, the biological tests yielded negative results also under normal conditions of sterilization.

Cell biology of the Koji mold Aspergillus oryzae.

PubMed

Kitamoto, Katsuhiko

2015-01-01

Koji mold, Aspergillus oryzae, has been used for the production of sake, miso, and soy sauce for more than one thousand years in Japan. Due to the importance, A. oryzae has been designated as the national micro-organism of Japan (Koku-kin). A. oryzae has been intensively studied in the past century, with most investigations focusing on breeding techniques and developing methods for Koji making for sake brewing. However, the understanding of fundamental biology of A. oryzae remains relatively limited compared with the yeast Saccharomyces cerevisiae. Therefore, we have focused on studying the cell biology including live cell imaging of organelles, protein vesicular trafficking, autophagy, and Woronin body functions using the available genomic information. In this review, I describe essential findings of cell biology of A. oryzae obtained in our study for a quarter of century. Understanding of the basic biology will be critical for not its biotechnological application, but also for an understanding of the fundamental biology of other filamentous fungi.

Highlighting the Need for Systems-Level Experimental Characterization of Plant Metabolic Enzymes.

PubMed

Engqvist, Martin K M

2016-01-01

The biology of living organisms is determined by the action and interaction of a large number of individual gene products, each with specific functions. Discovering and annotating the function of gene products is key to our understanding of these organisms. Controlled experiments and bioinformatic predictions both contribute to functional gene annotation. For most species it is difficult to gain an overview of what portion of gene annotations are based on experiments and what portion represent predictions. Here, I survey the current state of experimental knowledge of enzymes and metabolism in Arabidopsis thaliana as well as eleven economically important crops and forestry trees - with a particular focus on reactions involving organic acids in central metabolism. I illustrate the limited availability of experimental data for functional annotation of enzymes in most of these species. Many enzymes involved in metabolism of citrate, malate, fumarate, lactate, and glycolate in crops and forestry trees have not been characterized. Furthermore, enzymes involved in key biosynthetic pathways which shape important traits in crops and forestry trees have not been characterized. I argue for the development of novel high-throughput platforms with which limited functional characterization of gene products can be performed quickly and relatively cheaply. I refer to this approach as systems-level experimental characterization. The data collected from such platforms would form a layer intermediate between bioinformatic gene function predictions and in-depth experimental studies of these functions. Such a data layer would greatly aid in the pursuit of understanding a multiplicity of biological processes in living organisms.

Role of temperature dependence of optical properties in laser irradiation of biological tissue

NASA Astrophysics Data System (ADS)

Rastegar, Sohi; Kim, Beop-Min; Jacques, Steven L.

1992-08-01

Optical properties of biological tissue can change as a result of thermal denaturation due to temperature rise; a familiar example is whitening observed in cooking egg-white. Changes in optical properties with temperature have been reported in the literature. Temperature rise due to laser irradiation is a function of the optical properties of tissue which themselves are a function of temperature of the tissue. This creates a coupling between light and temperature fields for biological tissue under laser irradiation. The effects of this coupling on the temperature response and light distribution may play an important role in dosimetry consideration for therapeutic as well as diagnostic application of lasers in medicine. In a previous study this problem was addressed in one dimension, for short irradiation exposures, using certain simplifying assumptions. The purpose of this research was to develop a mathematical model for dynamic optical changes with thermal denaturation and a computer program for simulation of these effects for a multi-dimensional geometry.

What is biodiversity? Stepping forward from barcoding to understanding biological differences.

PubMed

Nikinmaa, Mikko

2014-10-01

This opinion paper gives personal views of the direction that cataloguing biodiversity should be going in. Although molecular taxonomy enables rapid and high throughput identification of species, it needs to be anchored to traditional taxonomy, because without information of actual biological properties of species, DNA barcoding just reports differences in selected DNA sequences, which need not have anything to do with the biological properties of the organisms, and the reasons for the development of the species. Since functional differences are the most common reason behind species differences, the future of cataloguing biodiversity and biodiversity research is, in my opinion, in trying to integrate genomic research to comparative physiology in order to be able to evaluate which functional properties have likely been important in generating biodiversity. This task is overwhelming, and requires forgetting the traditional disciplines. Further, major problems associated with the present-day treatment of genomic data are presented from my viewpoint. Copyright © 2014 Elsevier B.V. All rights reserved.

Targeting Deacetylases to Improve Outcomes after Allogeneic Bone Marrow Transplantation

PubMed Central

Reddy, Pavan

2013-01-01

Graft-versus-host disease (GVHD) is the major complication of allogeneic bone marrow transplantation (BMT). GVHD is a complex immunologically mediated biological process. Recent data have shown that histone deacetylase inhibitors (HDACis) have potent anti-inflammatory effects. We have been studying the role of acetylation through inhibition of histone deacetylases (HDACs) in modulating immunity, specifically, GVHD. HDAC inhibition regulates GVHD, at least in part, through suppression of the function of host antigen presenting cells such as dendritic cells (DCs). HDACis reduce DC responses by enhancing the expression of indoleamine 2,3 dioxygenase (IDO) in a STAT-3–dependent manner. They also alter the function of other immune cells such as T regulatory cells and NK cells, which also play important roles in the biology of GVHD. Based on these observations, a clinical trial has been launched to evaluate its impact on clinical GVHD. The clinical features, biology of GVHD, the experimental studies with HDACis, and preliminary observations from humans are discussed. PMID:23874019

Bioengineering of plant (tri)terpenoids: from metabolic engineering of plants to synthetic biology in vivo and in vitro.

PubMed

Moses, Tessa; Pollier, Jacob; Thevelein, Johan M; Goossens, Alain

2013-10-01

Terpenoids constitute a large and diverse class of natural products that serve many functions in nature. Most of the tens of thousands of the discovered terpenoids are synthesized by plants, where they function as primary metabolites involved in growth and development, or as secondary metabolites that optimize the interaction between the plant and its environment. Several plant terpenoids are economically important molecules that serve many applications as pharmaceuticals, pesticides, etc. Major challenges for the commercialization of plant-derived terpenoids include their low production levels in planta and the continuous demand of industry for novel molecules with new or superior biological activities. Here, we highlight several synthetic biology methods to enhance and diversify the production of plant terpenoids, with a foresight towards triterpenoid engineering, the least engineered class of bioactive terpenoids. Increased or cheaper production of valuable triterpenoids may be obtained by 'classic' metabolic engineering of plants or by heterologous production of the compounds in other plants or microbes. Novel triterpenoid structures can be generated through combinatorial biosynthesis or directed enzyme evolution approaches. In its ultimate form, synthetic biology may lead to the production of large amounts of plant triterpenoids in in vitro systems or custom-designed artificial biological systems. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Mass Spectrometry-Based Metabolomics to Elucidate Functions in Marine Organisms and Ecosystems

PubMed Central

Goulitquer, Sophie; Potin, Philippe; Tonon, Thierry

2012-01-01

Marine systems are very diverse and recognized as being sources of a wide range of biomolecules. This review provides an overview of metabolite profiling based on mass spectrometry (MS) approaches in marine organisms and their environments, focusing on recent advances in the field. We also point out some of the technical challenges that need to be overcome in order to increase applications of metabolomics in marine systems, including extraction of chemical compounds from different matrices and data management. Metabolites being important links between genotype and phenotype, we describe added value provided by integration of data from metabolite profiling with other layers of omics, as well as their importance for the development of systems biology approaches in marine systems to study several biological processes, and to analyze interactions between organisms within communities. The growing importance of MS-based metabolomics in chemical ecology studies in marine ecosystems is also illustrated. PMID:22690147

Proton transfer from imidazole to chloranil studied by FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Sharma, Amit

2018-05-01

Imidazole is incorporated into many important biological molecules. The most obvious is the amino acid histidine, which has an imidazole side chain. Histidine is present in many proteins and enzymes and plays a vital part in the structure and binding functions of hemoglobin. Therefore it is important to study its proton transfer property. In the present work proton transfer from imidazole to chloranil is investigated by Fourier Transform Infra red Spectroscopy.

GeneSCF: a real-time based functional enrichment tool with support for multiple organisms.

PubMed

Subhash, Santhilal; Kanduri, Chandrasekhar

2016-09-13

High-throughput technologies such as ChIP-sequencing, RNA-sequencing, DNA sequencing and quantitative metabolomics generate a huge volume of data. Researchers often rely on functional enrichment tools to interpret the biological significance of the affected genes from these high-throughput studies. However, currently available functional enrichment tools need to be updated frequently to adapt to new entries from the functional database repositories. Hence there is a need for a simplified tool that can perform functional enrichment analysis by using updated information directly from the source databases such as KEGG, Reactome or Gene Ontology etc. In this study, we focused on designing a command-line tool called GeneSCF (Gene Set Clustering based on Functional annotations), that can predict the functionally relevant biological information for a set of genes in a real-time updated manner. It is designed to handle information from more than 4000 organisms from freely available prominent functional databases like KEGG, Reactome and Gene Ontology. We successfully employed our tool on two of published datasets to predict the biologically relevant functional information. The core features of this tool were tested on Linux machines without the need for installation of more dependencies. GeneSCF is more reliable compared to other enrichment tools because of its ability to use reference functional databases in real-time to perform enrichment analysis. It is an easy-to-integrate tool with other pipelines available for downstream analysis of high-throughput data. More importantly, GeneSCF can run multiple gene lists simultaneously on different organisms thereby saving time for the users. Since the tool is designed to be ready-to-use, there is no need for any complex compilation and installation procedures.

Differences in Retinal Structure and Function between Aging Male and Female Sprague-Dawley Rats are Strongly Influenced by the Estrus Cycle

PubMed Central

Chaychi, Samaneh; Polosa, Anna; Lachapelle, Pierre

2015-01-01

Purpose Biological sex and age are considered as two important factors that may influence the function and structure of the retina, an effect that might be governed by sexual hormones such as estrogen. The purpose of this study was to delineate the influence that biological sex and age exert on the retinal function and structure of rodents and also clarify the effect that the estrus cycle might exert on the retinal function of female rats. Method The retinal function of 50 normal male and female albino Sprague-Dawley (SD) rats was investigated with the electroretinogram (ERG) at postnatal day (P) 30, 60, 100, 200, and 300 (n = 5–6 male and female rats/age). Following the ERG recording sessions, retinal histology was performed in both sexes. In parallel, the retinal function of premenopausal and menopausal female rats aged P540 were also compared. Results Sex and age-related changes in retinal structure and function were observed in our animal model. However, irrespective of age, no significant difference was observed in ERG and retinal histology obtained from male and female rats. Notwithstanding the above we did however notice that between P60 and P200 there was a gradual increase in ERG amplitudes of female rats compared to males. Furthermore, the ERG of premenopausal female rats aged 18 months old (P540) was larger compared to age-matched menopausal female rats as well as that of male rats. Conclusion Our results showed that biological sex and age can influence the retinal function and structure of albino SD rats. Furthermore, we showed that cycled female rats have better retinal function compared to the menopausal female rats suggesting a beneficial effect of the estrus cycle on the retinal function. PMID:26317201

Chemical and Enzymatic Strategies for Bacterial and Mammalian Cell Surface Engineering.

PubMed

Bi, Xiaobao; Yin, Juan; Chen Guanbang, Ashley; Liu, Chuan-Fa

2018-06-07

The cell surface serves important functions such as the regulation of cell-cell and cell-environment interactions. The understanding and manipulation of the cell surface is important for a wide range of fundamental studies of cellular behavior and for biotechnological and medical applications. With the rapid advance of biology, chemistry and materials science, many strategies have been developed for the functionalization of bacterial and mammalian cell surfaces. Here, we review the recent development of chemical and enzymatic approaches to cell surface engineering with particular emphasis on discussing the advantages and limitations of each of these strategies. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bioactivation of particles

DOEpatents

Pinaud, Fabien [Berkeley, CA; King, David [San Francisco, CA; Weiss, Shimon [Los Angeles, CA

2011-08-16

Particles are bioactivated by attaching bioactivation peptides to the particle surface. The bioactivation peptides are peptide-based compounds that impart one or more biologically important functions to the particles. Each bioactivation peptide includes a molecular or surface recognition part that binds with the surface of the particle and one or more functional parts. The surface recognition part includes an amino-end and a carboxy-end and is composed of one or more hydrophobic spacers and one or more binding clusters. The functional part(s) is attached to the surface recognition part at the amino-end and/or said carboxy-end.

Proteins and Their Interacting Partners: An Introduction to Protein-Ligand Binding Site Prediction Methods.

PubMed

Roche, Daniel Barry; Brackenridge, Danielle Allison; McGuffin, Liam James

2015-12-15

Elucidating the biological and biochemical roles of proteins, and subsequently determining their interacting partners, can be difficult and time consuming using in vitro and/or in vivo methods, and consequently the majority of newly sequenced proteins will have unknown structures and functions. However, in silico methods for predicting protein-ligand binding sites and protein biochemical functions offer an alternative practical solution. The characterisation of protein-ligand binding sites is essential for investigating new functional roles, which can impact the major biological research spheres of health, food, and energy security. In this review we discuss the role in silico methods play in 3D modelling of protein-ligand binding sites, along with their role in predicting biochemical functionality. In addition, we describe in detail some of the key alternative in silico prediction approaches that are available, as well as discussing the Critical Assessment of Techniques for Protein Structure Prediction (CASP) and the Continuous Automated Model EvaluatiOn (CAMEO) projects, and their impact on developments in the field. Furthermore, we discuss the importance of protein function prediction methods for tackling 21st century problems.

Dynamics of active sites in biological macromolecules using a Green-function approach: An application to heme vibrational dynamics in myoglobin

NASA Astrophysics Data System (ADS)

Rai, Brajesh; Prohofsky, Earl

2003-03-01

Dynamics of functionally active regions of biological macromolecules can be studied using a Green-function technique. This approach uses the fact that in most cases one has a good set of force constants for active sites, and rather poorly defined force field parameters for other regions of the macromolecule. The Green-function method is applied to study the iron vibrational modes of the heme active site in myoglobin. In this approach, the heme active site is viewed as a system interacting with surrounding globin, which acts as an excitation bath. The normal modes of heme and globin are separately calculated using the best available force fields for the two entities. The iron vibrational spectrum of myoglobin is then obtained using the solutions of the heme and globin, and by considering physically meaningful interactions between the two units. The refinement of the Green-function calculations to the experimental data from an x-ray synchrotron-based Nuclear Resonance Vibrational Spectroscopy provides important insights into the character of iron normal modes of myoglobin.

MultitaskProtDB: a database of multitasking proteins.

PubMed

Hernández, Sergio; Ferragut, Gabriela; Amela, Isaac; Perez-Pons, JosepAntoni; Piñol, Jaume; Mozo-Villarias, Angel; Cedano, Juan; Querol, Enrique

2014-01-01

We have compiled MultitaskProtDB, available online at http://wallace.uab.es/multitask, to provide a repository where the many multitasking proteins found in the literature can be stored. Multitasking or moonlighting is the capability of some proteins to execute two or more biological functions. Usually, multitasking proteins are experimentally revealed by serendipity. This ability of proteins to perform multitasking functions helps us to understand one of the ways used by cells to perform many complex functions with a limited number of genes. Even so, the study of this phenomenon is complex because, among other things, there is no database of moonlighting proteins. The existence of such a tool facilitates the collection and dissemination of these important data. This work reports the database, MultitaskProtDB, which is designed as a friendly user web page containing >288 multitasking proteins with their NCBI and UniProt accession numbers, canonical and additional biological functions, monomeric/oligomeric states, PDB codes when available and bibliographic references. This database also serves to gain insight into some characteristics of multitasking proteins such as frequencies of the different pairs of functions, phylogenetic conservation and so forth.

Detecting subnetwork-level dynamic correlations.

PubMed

Yan, Yan; Qiu, Shangzhao; Jin, Zhuxuan; Gong, Sihong; Bai, Yun; Lu, Jianwei; Yu, Tianwei

2017-01-15

The biological regulatory system is highly dynamic. The correlations between many functionally related genes change over different biological conditions. Finding dynamic relations on the existing biological network may reveal important regulatory mechanisms. Currently no method is available to detect subnetwork-level dynamic correlations systematically on the genome-scale network. Two major issues hampered the development. The first is gene expression profiling data usually do not contain time course measurements to facilitate the analysis of dynamic relations, which can be partially addressed by using certain genes as indicators of biological conditions. Secondly, it is unclear how to effectively delineate subnetworks, and define dynamic relations between them. Here we propose a new method named LANDD (Liquid Association for Network Dynamics Detection) to find subnetworks that show substantial dynamic correlations, as defined by subnetwork A is concentrated with Liquid Association scouting genes for subnetwork B. The method produces easily interpretable results because of its focus on subnetworks that tend to comprise functionally related genes. Also, the collective behaviour of genes in a subnetwork is a much more reliable indicator of underlying biological conditions compared to using single genes as indicators. We conducted extensive simulations to validate the method's ability to detect subnetwork-level dynamic correlations. Using a real gene expression dataset and the human protein-protein interaction network, we demonstrate the method links subnetworks of distinct biological processes, with both confirmed relations and plausible new functional implications. We also found signal transduction pathways tend to show extensive dynamic relations with other functional groups. The R package is available at https://cran.r-project.org/web/packages/LANDD CONTACTS: yunba@pcom.edu, jwlu33@hotmail.com or tianwei.yu@emory.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

PubMed

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

2013-12-01

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

Chemoprofile and functional diversity of fungal and bacterial endophytes and role of ecofactors - A review.

PubMed

Shah, Aiyatullah; Hassan, Qazi Parvaiz; Mushtaq, Saleem; Shah, Aabid Manzoor; Hussain, Aehtesham

2017-10-01

Endophytes represent a hidden world within plants. Almost all plants that are studied harbor one or more endophytes, which help their host to survive against pathogens and changing adverse environmental conditions. Fungal and bacterial endophytes with distinct ecological niches show important biological activities and ecological functions. Their unique physiological and biochemical characteristics lead to the production of niche specific secondary metabolites that may have pharmacological potential. Identification of specific secondary metabolites in adverse environment can also help us in understanding mechanisms of host tolerance against stress condition such as biological invasions, salt, drought, temperature. These metabolites include micro as well as macromolecules, which they produce through least studied yet surprising mechanisms like xenohormesis, toxin-antitoxin system, quorum sensing. Therefore, future studies should focus on unfolding all the underlying molecular mechanisms as well as the impact of physical and biochemical environment of a specific host over endophytic function and metabolite elicitation. Need of the hour is to reshape the focus of research over endophytes and scientifically drive their ecological role toward prospective pharmacological as well as eco-friendly biological applications. This may help to manage these endophytes especially from untapped ecoregions as a useful undying biological tool to meet the present challenges as well as lay a strong and logical basis for any impending challenges. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Expression atlas and comparative coexpression network analyses reveal important genes involved in the formation of lignified cell wall in Brachypodium distachyon.

PubMed

Sibout, Richard; Proost, Sebastian; Hansen, Bjoern Oest; Vaid, Neha; Giorgi, Federico M; Ho-Yue-Kuang, Severine; Legée, Frédéric; Cézart, Laurent; Bouchabké-Coussa, Oumaya; Soulhat, Camille; Provart, Nicholas; Pasha, Asher; Le Bris, Philippe; Roujol, David; Hofte, Herman; Jamet, Elisabeth; Lapierre, Catherine; Persson, Staffan; Mutwil, Marek

2017-08-01

While Brachypodium distachyon (Brachypodium) is an emerging model for grasses, no expression atlas or gene coexpression network is available. Such tools are of high importance to provide insights into the function of Brachypodium genes. We present a detailed Brachypodium expression atlas, capturing gene expression in its major organs at different developmental stages. The data were integrated into a large-scale coexpression database ( www.gene2function.de), enabling identification of duplicated pathways and conserved processes across 10 plant species, thus allowing genome-wide inference of gene function. We highlight the importance of the atlas and the platform through the identification of duplicated cell wall modules, and show that a lignin biosynthesis module is conserved across angiosperms. We identified and functionally characterised a putative ferulate 5-hydroxylase gene through overexpression of it in Brachypodium, which resulted in an increase in lignin syringyl units and reduced lignin content of mature stems, and led to improved saccharification of the stem biomass. Our Brachypodium expression atlas thus provides a powerful resource to reveal functionally related genes, which may advance our understanding of important biological processes in grasses. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Sucrose metabolism gene families and their biological functions

PubMed Central

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

2015-01-01

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

Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. Lipidomics: a global approach to lipid analysis in biological systems.

PubMed

Watson, Andrew D

2006-10-01

Lipids are water-insoluble molecules that have a wide variety of functions within cells, including: 1) maintenance of electrochemical gradients; 2) subcellular partitioning; 3) first- and second-messenger cell signaling; 4) energy storage; and 5) protein trafficking and membrane anchoring. The physiological importance of lipids is illustrated by the numerous diseases to which lipid abnormalities contribute, including atherosclerosis, diabetes, obesity, and Alzheimer's disease. Lipidomics, a branch of metabolomics, is a systems-based study of all lipids, the molecules with which they interact, and their function within the cell. Recent advances in soft-ionization mass spectrometry, combined with established separation techniques, have allowed the rapid and sensitive detection of a variety of lipid species with minimal sample preparation. A "lipid profile" from a crude lipid extract is a mass spectrum of the composition and abundance of the lipids it contains, which can be used to monitor changes over time and in response to particular stimuli. Lipidomics, integrated with genomics, proteomics, and metabolomics, will contribute toward understanding how lipids function in a biological system and will provide a powerful tool for elucidating the mechanism of lipid-based disease, for biomarker screening, and for monitoring pharmacologic therapy.

Robust biological parametric mapping: an improved technique for multimodal brain image analysis

NASA Astrophysics Data System (ADS)

Yang, Xue; Beason-Held, Lori; Resnick, Susan M.; Landman, Bennett A.

2011-03-01

Mapping the quantitative relationship between structure and function in the human brain is an important and challenging problem. Numerous volumetric, surface, region of interest and voxelwise image processing techniques have been developed to statistically assess potential correlations between imaging and non-imaging metrics. Recently, biological parametric mapping has extended the widely popular statistical parametric approach to enable application of the general linear model to multiple image modalities (both for regressors and regressands) along with scalar valued observations. This approach offers great promise for direct, voxelwise assessment of structural and functional relationships with multiple imaging modalities. However, as presented, the biological parametric mapping approach is not robust to outliers and may lead to invalid inferences (e.g., artifactual low p-values) due to slight mis-registration or variation in anatomy between subjects. To enable widespread application of this approach, we introduce robust regression and robust inference in the neuroimaging context of application of the general linear model. Through simulation and empirical studies, we demonstrate that our robust approach reduces sensitivity to outliers without substantial degradation in power. The robust approach and associated software package provides a reliable way to quantitatively assess voxelwise correlations between structural and functional neuroimaging modalities.

Handling gene and protein names in the age of bioinformatics: the special challenge of secreted multimodular bacterial enzymes such as the cbhA/cbh9A gene of Clostridium thermocellum.

PubMed

Schwarz, Wolfgang H; Brunecky, Roman; Broeker, Jannis; Liebl, Wolfgang; Zverlov, Vladimir V

2018-02-26

An increasing number of researchers working in biology, biochemistry, biotechnology, bioengineering, bioinformatics and other related fields of science are using biological molecules. As the scientific background of the members of different scientific communities is more diverse than ever before, the number of scientists not familiar with the rules for non-ambiguous designation of genetic elements is increasing. However, with biological molecules gaining importance through biotechnology, their functional and unambiguous designation is vital. Unfortunately, naming genes and proteins is not an easy task. In addition, the traditional concepts of bioinformatics are challenged with the appearance of proteins comprising different modules with a respective function in each module. This article highlights basic rules and novel solutions in designation recently used within the community of bacterial geneticists, and we discuss the present-day handling of gene and protein designations. As an example we will utilize a recent mischaracterization of gene nomenclature. We make suggestions for better handling of names in future literature as well as in databases and annotation projects. Our methodology emphasizes the hydrolytic function of multi-modular genes and extracellular proteins from bacteria.

Ferroelectric switching of elastin

PubMed Central

Liu, Yuanming; Cai, Hong-Ling; Zelisko, Matthew; Wang, Yunjie; Sun, Jinglan; Yan, Fei; Ma, Feiyue; Wang, Peiqi; Chen, Qian Nataly; Zheng, Hairong; Meng, Xiangjian; Sharma, Pradeep; Zhang, Yanhang; Li, Jiangyu

2014-01-01

Ferroelectricity has long been speculated to have important biological functions, although its very existence in biology has never been firmly established. Here, we present compelling evidence that elastin, the key ECM protein found in connective tissues, is ferroelectric, and we elucidate the molecular mechanism of its switching. Nanoscale piezoresponse force microscopy and macroscopic pyroelectric measurements both show that elastin retains ferroelectricity at 473 K, with polarization on the order of 1 μC/cm2, whereas coarse-grained molecular dynamics simulations predict similar polarization with a Curie temperature of 580 K, which is higher than most synthetic molecular ferroelectrics. The polarization of elastin is found to be intrinsic in tropoelastin at the monomer level, analogous to the unit cell level polarization in classical perovskite ferroelectrics, and it switches via thermally activated cooperative rotation of dipoles. Our study sheds light onto a long-standing question on ferroelectric switching in biology and establishes ferroelectricity as an important biophysical property of proteins. This is a critical first step toward resolving its physiological significance and pathological implications. PMID:24958890

Effects of Phospholipase C on Fusarium graminearum Growth and Development.

PubMed

Zhu, Qili; Zhou, Benguo; Gao, Zhengliang; Liang, Yuancun

2015-12-01

Phospholipase C (PLC) plays important roles in regulating various biological processes in eukaryotes. Currently, little is known about the function of PLC in filamentous fungi, especially the plant pathogenic fungi. Fusarium graminearum is the causal agent of Fusarium head blight in many cereal crops. BLAST search revealed that Fusarium genome contains six FgPLC genes. Using quantitative RT-PCR, different FgPLC gene expressions in mycelia were analyzed. To investigate the role of FgPLC in F. graminearum biology, a pharmacological study using a known inhibitor of PLC (U73122) was conducted. Results showed that inhibition of FgPLC resulted in significant alterations of mycelial growth, conidiation, conidial germination, perithecium formation, and expressions of Tri5 and Tri6 genes. As expected, the treatment of F. graminearum with U73343, an inactive analog of U73122, showed no effect on F. graminearum biology. Our results suggested strongly that FgPLC plays important roles in F. graminearum growth and development.

Neuropeptide Substance P and the Immune Response

PubMed Central

Tehrani, Mohsen; Grace, Peter M.; Pothoulakis, Charalabos; Dana, Reza

2016-01-01

Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of activity of immune cells. This Review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immuno-biology of substance P and we discuss the clinical implications of its ability to modulate the immune response. PMID:27314883

The implications of non-linear biological oscillations on human electrophysiology for electrohypersensitivity (EHS) and multiple chemical sensitivity (MCS).

PubMed

Sage, Cindy

2015-01-01

The 'informational content' of Earth's electromagnetic signaling is like a set of operating instructions for human life. These environmental cues are dynamic and involve exquisitely low inputs (intensities) of critical frequencies with which all life on Earth evolved. Circadian and other temporal biological rhythms depend on these fluctuating electromagnetic inputs to direct gene expression, cell communication and metabolism, neural development, brainwave activity, neural synchrony, a diversity of immune functions, sleep and wake cycles, behavior and cognition. Oscillation is also a universal phenomenon, and biological systems of the heart, brain and gut are dependent on the cooperative actions of cells that function according to principles of non-linear, coupled biological oscillations for their synchrony. They are dependent on exquisitely timed cues from the environment at vanishingly small levels. Altered 'informational content' of environmental cues can swamp natural electromagnetic cues and result in dysregulation of normal biological rhythms that direct growth, development, metabolism and repair mechanisms. Pulsed electromagnetic fields (PEMF) and radiofrequency radiation (RFR) can have the devastating biological effects of disrupting homeostasis and desynchronizing normal biological rhythms that maintain health. Non-linear, weak field biological oscillations govern body electrophysiology, organize cell and tissue functions and maintain organ systems. Artificial bioelectrical interference can give false information (disruptive signaling) sufficient to affect critical pacemaker cells (of the heart, gut and brain) and desynchronize functions of these important cells that orchestrate function and maintain health. Chronic physiological stress undermines homeostasis whether it is chemically induced or electromagnetically induced (or both exposures are simultaneous contributors). This can eventually break down adaptive biological responses critical to health maintenance; and resilience can be compromised. Electrohypersensitivity can be caused by successive assaults on human bioelectrochemical dynamics from exogenous electromagnetic fields (EMF) and RFR or a single acute exposure. Once sensitized, further exposures are widely reported to cause reactivity to lower and lower intensities of EMF/RFR, at which point thousand-fold lower levels can cause adverse health impacts to the electrosensitive person. Electrohypersensitivity (EHS) can be a precursor to, or linked with, multiple chemical sensitivity (MCS) based on reports of individuals who first develop one condition, then rapidly develop the other. Similarity of chemical biomarkers is seen in both conditions [histamines, markers of oxidative stress, auto-antibodies, heat shock protein (HSP), melatonin markers and leakage of the blood-brain barrier]. Low intensity pulsed microwave activation of voltage-gated calcium channels (VGCCs) is postulated as a mechanism of action for non-thermal health effects.

OmicsNet: a web-based tool for creation and visual analysis of biological networks in 3D space.

PubMed

Zhou, Guangyan; Xia, Jianguo

2018-06-07

Biological networks play increasingly important roles in omics data integration and systems biology. Over the past decade, many excellent tools have been developed to support creation, analysis and visualization of biological networks. However, important limitations remain: most tools are standalone programs, the majority of them focus on protein-protein interaction (PPI) or metabolic networks, and visualizations often suffer from 'hairball' effects when networks become large. To help address these limitations, we developed OmicsNet - a novel web-based tool that allows users to easily create different types of molecular interaction networks and visually explore them in a three-dimensional (3D) space. Users can upload one or multiple lists of molecules of interest (genes/proteins, microRNAs, transcription factors or metabolites) to create and merge different types of biological networks. The 3D network visualization system was implemented using the powerful Web Graphics Library (WebGL) technology that works natively in most major browsers. OmicsNet supports force-directed layout, multi-layered perspective layout, as well as spherical layout to help visualize and navigate complex networks. A rich set of functions have been implemented to allow users to perform coloring, shading, topology analysis, and enrichment analysis. OmicsNet is freely available at http://www.omicsnet.ca.

Biological Hydropersulfides and Related Polysulfides: A New Concept and Perspective in Redox Biology.

PubMed

Fukuto, Jon M; Ignarro, Louis J; Nagy, Peter; Wink, David A; Kevil, Christopher G; Feelisch, Martin; Cortese-Krott, Miriam M; Bianco, Christopher L; Kumagai, Yoshito; Hobbs, Adrian J; Lin, Joseph; Ida, Tomoaki; Akaike, Takaaki

2018-05-12

The chemical biology of thiols (RSH, e.g., cysteine and cysteine containing proteins/peptides) has been a topic of extreme interest for many decades due to their reported roles in protein structure/folding, redox signaling, metal ligation, cellular protection and enzymology. While many of the studies on thiol/sulfur biochemistry have focused on thiols, relatively ignored have been hydropersulfides (RSSH) and higher order polysulfur species (RSS n H, RSS n R, n > 1). Recent and provocative work has alluded to the prevalence and likely physiological importance of RSSH and related RSS n H. RSSH of cysteine (Cys-SSH) has been found to be prevalent in mammalian systems along with Cys-SSH-containing proteins. The RSSH functionality has not been examined to the extent of other biologically relevant sulfur derivatives (e.g., sulfenic acids, disulfides, etc.), whose roles in cell signaling are strongly indicated. The recent finding of Cys-SSH biosynthesis and translational incorporation into proteins is an unequivocal indication of its fundamental importance and necessitates a more profound look into the physiology of RSSH. In this Review, we discuss the currently reported chemical biology of RSSH (and related species) as a prelude to discussing their possible physiological roles. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Whipworm kinomes reflect a unique biology and adaptation to the host animal.

PubMed

Stroehlein, Andreas J; Young, Neil D; Korhonen, Pasi K; Chang, Bill C H; Nejsum, Peter; Pozio, Edoardo; La Rosa, Giuseppe; Sternberg, Paul W; Gasser, Robin B

2017-11-01

Roundworms belong to a diverse phylum (Nematoda) which is comprised of many parasitic species including whipworms (genus Trichuris). These worms have adapted to a biological niche within the host and exhibit unique morphological characteristics compared with other nematodes. Although these adaptations are known, the underlying molecular mechanisms remain elusive. The availability of genomes and transcriptomes of some whipworms now enables detailed studies of their molecular biology. Here, we defined and curated the full complement of an important class of enzymes, the protein kinases (kinomes) of two species of Trichuris, using an advanced and integrated bioinformatic pipeline. We investigated the transcription of Trichuris suis kinase genes across developmental stages, sexes and tissues, and reveal that selectively transcribed genes can be linked to central roles in developmental and reproductive processes. We also classified and functionally annotated the curated kinomes by integrating evidence from structural modelling and pathway analyses, and compared them with other curated kinomes of phylogenetically diverse nematode species. Our findings suggest unique adaptations in signalling processes governing worm morphology and biology, and provide an important resource that should facilitate experimental investigations of kinases and the biology of signalling pathways in nematodes. Copyright © 2017 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Analysis of terahertz dielectric properties of pork tissue

NASA Astrophysics Data System (ADS)

Huang, Yuqing; Xie, Qiaoling; Sun, Ping

2017-10-01

Seeing that about 70% component of fresh biological tissues is water, many scientists try to use water models to describe the dielectric properties of biological tissues. The classical water dielectric models are Debye model, Double Debye model and Cole-Cole model. This work aims to determine a suitable model by comparing three models above with experimental data. These models are applied to fresh pork tissue. By means of least square method, the parameters of different models are fitted with the experimental data. Comparing different models on both dielectric function, the Cole-Cole model is verified the best to describe the experiments of pork tissue. The correction factor α of the Cole-Cole model is an important modification for biological tissues. So Cole-Cole model is supposed to be a priority selection to describe the dielectric properties for biological tissues in the terahertz range.

Functional networks inference from rule-based machine learning models.

PubMed

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

2016-01-01

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

Increased dielectric constant in the water treated by extremely low frequency electromagnetic field and its possible biological implication

NASA Astrophysics Data System (ADS)

Shen, Xun

2011-12-01

Water is the most abundant compound on the surface of the Earth, and can be considered to be the most important molecule in living systems. Water plays a variety of cellular functions, being the solvent of most biological molecules, a substrate and product of enzymatic catalysis, an important component of macromolecules, and more. Because of importance of water in life, many physical and chemical treatments were invented to improve the quality of drinking water. Among them, the treatment with electromagnetic field is a well-known, but much debatable physical method. Although electromagnetic field has been utilized for treating water for 80 years, many reports on beneficial biological effect of electromagnetic field-treated water were either anecdotal or less convincing. To explore if there is any physical base for understanding possible biological effects of electromagnetic field-treated water, dielectric relaxation spectra of deionized water treated with an extremely low frequency electromagnetic (ELFEM) field were measured and compared with that of untreated water. It was surprisingly found that the dielectric constant of the ELFEM field-treated water was 3.7% higher than the control over the frequency range of 1-10 GHz, which indicates a higher molecular polarization occurs in the ELFEM field-treated water. Electrostatic and thermodynamic analysis shows that proteins or other biomacromolecules would have more reduced free energy when they are hydrated in high dielectric constant water. Since free energy is of crucial importance for stability of proteins, protein folding and its conformational change, as well as catalytic activity of enzymes, the free energy reduction of the biomacromolecules hydrated with higher dielectric constant water may be responsible for many possible biological effects of electromagnetic field treated water.

Experimental design and reporting standards for metabolomics studies of mammalian cell lines.

PubMed

Hayton, Sarah; Maker, Garth L; Mullaney, Ian; Trengove, Robert D

2017-12-01

Metabolomics is an analytical technique that investigates the small biochemical molecules present within a biological sample isolated from a plant, animal, or cultured cells. It can be an extremely powerful tool in elucidating the specific metabolic changes within a biological system in response to an environmental challenge such as disease, infection, drugs, or toxins. A historically difficult step in the metabolomics pipeline is in data interpretation to a meaningful biological context, for such high-variability biological samples and in untargeted metabolomics studies that are hypothesis-generating by design. One way to achieve stronger biological context of metabolomic data is via the use of cultured cell models, particularly for mammalian biological systems. The benefits of in vitro metabolomics include a much greater control of external variables and no ethical concerns. The current concerns are with inconsistencies in experimental procedures and level of reporting standards between different studies. This review discusses some of these discrepancies between recent studies, such as metabolite extraction and data normalisation. The aim of this review is to highlight the importance of a standardised experimental approach to any cultured cell metabolomics study and suggests an example procedure fully inclusive of information that should be disclosed in regard to the cell type/s used and their culture conditions. Metabolomics of cultured cells has the potential to uncover previously unknown information about cell biology, functions and response mechanisms, and so the accurate biological interpretation of the data produced and its ability to be compared to other studies should be considered vitally important.

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

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

Ekworomadu, MarCia T.; Poor, Catherine B.; Owens, Cedric P.

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-positivemore » 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 upstream ligands.« less

Lateral organization, bilayer asymmetry, and inter-leaflet coupling of biological membranes

DOE PAGES

Smith, Jeremy C.; Cheng, Xiaolin; Nickels, Jonathan D.

2015-07-29

Understanding of cell membrane organization has evolved significantly from the classic fluid mosaic model. It is now recognized that biological membranes are highly organized structures, with differences in lipid compositions between inner and outer leaflets and in lateral structures within the bilayer plane, known as lipid rafts. These organizing principles are important for protein localization and function as well as cellular signaling. However, the mechanisms and biophysical basis of lipid raft formation, structure, dynamics and function are not clearly understood. One key question, which we focus on in this review, is how lateral organization and leaflet compositional asymmetry are coupled.more » Detailed information elucidating this question has been sparse because of the small size and transient nature of rafts and the experimental challenges in constructing asymmetric bilayers. Resolving this mystery will require advances in both experimentation and modeling. We discuss here the preparation of model systems along with experimental and computational approaches that have been applied in efforts to address this key question in membrane biology. Furthermore, we seek to place recent and future advances in experimental and computational techniques in context, providing insight into in-plane and transverse organization of biological membranes.« less

Biological features of hepatitis B virus isolates from patients based on full-length genomic analysis.

PubMed

Wen, Yu-Mei; Wang, Yong-Xiang

2009-01-01

The mechanisms for HBV persistence and the pathogenesis of chronic HB have been shown mainly due to defects in host immune responses. However, HBV isolates with different biological features may also contribute to different clinical outcomes and epidemiological implications in viral hepatitis B (HB). This review presents interesting biological features of HBV isolates based on the structural and functional analysis of full-length HBV isolates from various patients. Among isolates from children after failure of HB vaccination, 129L mutant at the 'a' determinant was found with normal binding efficiency to anti-HBs, but with reduced immunogenicity, which could initiate persistent HBV infections. Isolates from fulminant hepatitis (FH) B patients were not all highly replicative, but differences in capacities of anti-HBs induction could be involved in the pathogenesis of FH. The high replicative competency of isolates from hepatocellular carcinoma (HCC) patients could result in enhanced immune-mediated cytopathic effects against HBV viral proteins, and increased transactivating activity by the X protein. The mechanism of a double-spliced variant in enhancing replication of the wild-type virus is presented. The importance of integrating structural and functional analysis to reveal biological features of HBV isolates in viral pathogenesis is discussed.

Structured Water Layers Adjacent to Biological Membranes

PubMed Central

Higgins, Michael J.; Polcik, Martin; Fukuma, Takeshi; Sader, John E.; Nakayama, Yoshikazu; Jarvis, Suzanne P.

2006-01-01

Water amid the restricted space of crowded biological macromolecules and at membrane interfaces is essential for cell function, though the structure and function of this “biological water” itself remains poorly defined. The force required to remove strongly bound water is referred to as the hydration force and due to its widespread importance, it has been studied in numerous systems. Here, by using a highly sensitive dynamic atomic force microscope technique in conjunction with a carbon nanotube probe, we reveal a hydration force with an oscillatory profile that reflects the removal of up to five structured water layers from between the probe and biological membrane surface. Further, we find that the hydration force can be modified by changing the membrane fluidity. For 1,2-dipalmitoyl-sn-glycero-3-phosphocholine gel (Lβ) phase bilayers, each oscillation in the force profile indicates the force required to displace a single layer of water molecules from between the probe and bilayer. In contrast, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine fluid (Lα) phase bilayers at 60°C and 1,2-dioleoyl-sn-glycero-3-phosphocholine fluid (Lα) phase bilayers at 24°C seriously disrupt the molecular ordering of the water and result predominantly in a monotonic force profile. PMID:16798815

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

PubMed

Seeburg, P H

1993-08-01

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

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

PubMed

Seeburg, P H

1993-09-01

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

Multi-scale Functional and Molecular Photoacoustic Tomography

PubMed Central

Yao, Junjie; Xia, Jun; Wang, Lihong V.

2015-01-01

Photoacoustic tomography (PAT) combines rich optical absorption contrast with the high spatial resolution of ultrasound at depths in tissue. The high scalability of PAT has enabled anatomical imaging of biological structures ranging from organelles to organs. The inherent functional and molecular imaging capabilities of PAT have further allowed it to measure important physiological parameters and track critical cellular activities. Integration of PAT with other imaging technologies provides complementary capabilities and can potentially accelerate the clinical translation of PAT. PMID:25933617

Functionality of intrinsic disorder in tumor necrosis factor-α and its receptors.

PubMed

Uversky, Vladimir N; El-Baky, Nawal Abd; El-Fakharany, Esmail M; Sabry, Amira; Mattar, Ehab H; Uversky, Alexey V; Redwan, Elrashdy M

2017-11-01

Tumor necrosis factor-α (TNF-α) is a pleiotropic inflammatory cytokine that exerts potent cytotoxic effects on solid tumor cells, while not affecting their normal counterparts. It is also known that TNF-α exerts many of its biological functions via interaction with specific receptors. To understand the potential roles of intrinsic disorder in the functioning of this important cytokine, we explored the peculiarities of intrinsic disorder distribution in human TNF-α and its homologs from various species, ranging from zebrafish to chimpanzee. We also studied the peculiarities of intrinsic disorder distribution in human TNF-α receptors, TNFR1 and TNFR2. Analysis revealed that cytoplasmic domains of TNF-α and its receptors are expected to be highly disordered. Furthermore, although the sequence identities of analyzed TNF-α homologs range from 99.57% (between human and chimpanzee proteins) to 22.33% (between frog and fish proteins), their intrinsic disorder profiles are characterized by a remarkable similarity. These observations indicate that the peculiarities of distribution of the intrinsic disorder propensity within the amino acid sequences are evolutionary conserved, and therefore could be of functional importance for this family of proteins. We also show that disordered and flexible regions of human TNF-α and its TNFR1 and TNFR2 receptors are crucial for some of their biological activities. © 2017 Federation of European Biochemical Societies.

PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells

PubMed Central

He, Feng; Chen, Hairong; Probst-Kepper, Michael; Geffers, Robert; Eifes, Serge; del Sol, Antonio; Schughart, Klaus; Zeng, An-Ping; Balling, Rudi

2012-01-01

Human FOXP3+CD25+CD4+ regulatory T cells (Tregs) are essential to the maintenance of immune homeostasis. Several genes are known to be important for murine Tregs, but for human Tregs the genes and underlying molecular networks controlling the suppressor function still largely remain unclear. Here, we describe a strategy to identify the key genes directly from an undirected correlation network which we reconstruct from a very high time-resolution (HTR) transcriptome during the activation of human Tregs/CD4+ T-effector cells. We show that a predicted top-ranked new key gene PLAU (the plasminogen activator urokinase) is important for the suppressor function of both human and murine Tregs. Further analysis unveils that PLAU is particularly important for memory Tregs and that PLAU mediates Treg suppressor function via STAT5 and ERK signaling pathways. Our study demonstrates the potential for identifying novel key genes for complex dynamic biological processes using a network strategy based on HTR data, and reveals a critical role for PLAU in Treg suppressor function. PMID:23169000

Experimental annotation of post-translational features and translated coding regions in the pathogen Salmonella Typhimurium

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

Ansong, Charles; Tolic, Nikola; Purvine, Samuel O.

Complete and accurate genome annotation is crucial for comprehensive and systematic studies of biological systems. For example systems biology-oriented genome scale modeling efforts greatly benefit from accurate annotation of protein-coding genes to develop proper functioning models. However, determining protein-coding genes for most new genomes is almost completely performed by inference, using computational predictions with significant documented error rates (> 15%). Furthermore, gene prediction programs provide no information on biologically important post-translational processing events critical for protein function. With the ability to directly measure peptides arising from expressed proteins, mass spectrometry-based proteomics approaches can be used to augment and verify codingmore » regions of a genomic sequence and importantly detect post-translational processing events. In this study we utilized “shotgun” proteomics to guide accurate primary genome annotation of the bacterial pathogen Salmonella Typhimurium 14028 to facilitate a systems-level understanding of Salmonella biology. The data provides protein-level experimental confirmation for 44% of predicted protein-coding genes, suggests revisions to 48 genes assigned incorrect translational start sites, and uncovers 13 non-annotated genes missed by gene prediction programs. We also present a comprehensive analysis of post-translational processing events in Salmonella, revealing a wide range of complex chemical modifications (70 distinct modifications) and confirming more than 130 signal peptide and N-terminal methionine cleavage events in Salmonella. This study highlights several ways in which proteomics data applied during the primary stages of annotation can improve the quality of genome annotations, especially with regards to the annotation of mature protein products.« less

The great importance of normalization of LC-MS data for highly-accurate non-targeted metabolomics.

PubMed

Mizuno, Hajime; Ueda, Kazuki; Kobayashi, Yuta; Tsuyama, Naohiro; Todoroki, Kenichiro; Min, Jun Zhe; Toyo'oka, Toshimasa

2017-01-01

The non-targeted metabolomics analysis of biological samples is very important to understand biological functions and diseases. LC combined with electrospray ionization-based MS has been a powerful tool and widely used for metabolomic analyses. However, the ionization efficiency of electrospray ionization fluctuates for various unexpected reasons such as matrix effects and intraday variations of the instrument performances. To remove these fluctuations, normalization methods have been developed. Such techniques include increasing the sensitivity, separating co-eluting components and normalizing the ionization efficiencies. Normalization techniques allow simultaneously correcting of the ionization efficiencies of the detected metabolite peaks and achieving quantitative non-targeted metabolomics. In this review paper, we focused on these normalization methods for non-targeted metabolomics by LC-MS. Copyright © 2016 John Wiley & Sons, Ltd.

Brain Sex Matters: estrogen in cognition and Alzheimer’s disease

PubMed Central

Li, Rena; Cui, Jie; Shen, Yong

2014-01-01

Estrogens are the primary female sex hormones and play important roles in both reproductive and non-reproductive systems. Estrogens can be synthesized in non-reproductive tissues such as liver, heart, muscle, bone and the brain. During the past decade, increasing evidence suggests that brain estrogen can not only be synthesized by neurons, but also by astrocytes. Brain estrogen also works locally at the site of synthesis in paracrine and/or intracrine fashion to maintain important tissue-specific functions. Here, we will focus on the biology of brain estrogen and its impact on cognitive function and Alzheimer’s disease. This comprehensive review provides new insights into brain estrogens by presenting a better understanding of the tissue-specific estrogen effects and their roles in healthy ageing and cognitive function. PMID:24418360

Adolescent Survivors of Hurricane Katrina: A Pilot Study of Hypothalamic-Pituitary-Adrenal Axis Functioning

ERIC Educational Resources Information Center

Pfefferbaum, Betty; Tucker, Phebe; Nitiéma, Pascal

2015-01-01

Background: The hypothalamic-pituitary-adrenal (HPA) axis constitutes an important biological component of the stress response commonly studied through the measurement of cortisol. Limited research has examined HPA axis dysregulation in youth exposed to disasters. Objective: This study examined HPA axis activation in adolescent Hurricane Katrina…

A Framework for Understanding the Characteristics of Complexity in Biology

ERIC Educational Resources Information Center

Dauer, Joseph; Dauer, Jenny

2016-01-01

Understanding the functioning of natural systems is not easy, although there is general agreement that understanding complex systems is an important goal for science education. Defining what makes a natural system complex will assist in identifying gaps in research on student reasoning about systems. The goal of this commentary is to propose a…

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

USDA-ARS?s Scientific Manuscript database

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

Single-molecule sequencing and optical mapping yields an improved genome of woodland strawberry (Fragaria vesca) with chromosome-scale contiguity

USDA-ARS?s Scientific Manuscript database

Although draft genomes are available for most agronomically important plant species, the majority are incomplete, highly fragmented, and often riddled with assembly and scaffolding errors. These assembly issues hinder advances in tool development for functional genomics and systems biology. Here we ...

Cultural and Biological Adaptations to Deprivation: The Northern Ojibwa Case.

ERIC Educational Resources Information Center

Bishop, Charles A.

After the fur trade reached the Ojibwa during the early 17th Century, tribe structure and function rapidly changed. The intensity of social life increased as the Ojibwa and neighboring tribes gathered to exchange fur pelts for European items. Trade became so important that intertribal hostilities arose and an almost unrestrictive slaughter of…

Fire regimes and approaches for determining fire history

Treesearch

James K. Agee

1996-01-01

Fire has been an important evolutionary influence in forests, affecting species composition, structure, and functional aspects of forest biology. Restoration of wildland forests of the future will depend in part on restoring fire to an appropriate role in forest ecosystems. This may include the "range of natural variability" or other concepts associated with...

Bouncing Back by Moving Forward: Transactional Models of Risk and Resiliency. Revolutionary Studies in Child Psychology.

ERIC Educational Resources Information Center

Thurber, Christopher A.

2003-01-01

Four studies in child development show that children socialize parents as much as parents socialize children. Child development is a function of biological maturation and child-environment interaction. The most important determinants of resiliency are caregiver quality and socioeconomic status. Implications for camp are discussed, the most…

Cheatgrass and red brome; the history and biology of two invaders

Treesearch

Chad R. Reid; Sherel Goodrich; James E. Bowns

2008-01-01

In recent history, there has not been a more ecologically important event than the introduction of cheatgrass (Bromus tectorum) and red brome (Bromus rubens) into the Intermountain West. These grasses are very similar in ecology and history and are separated mostly by function of elevation. Both species are from the Mediterranean...

Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation

USDA-ARS?s Scientific Manuscript database

Sirtuin deacetylases and FOXO (Forkhead box, class O) transcription factors have important roles in many biological pathways, including cancer development. SIRT1 and SIRT2 deacetylate FOXO factors to regulate FOXO function. Because acetylation and ubiquitination both modify the '-amino group of lysi...

Extreme Arthropods: Exploring Evolutionary Adaptations to Polar and Temperate Deserts

ERIC Educational Resources Information Center

Sandro, Luke; Constible, Juanita M.; Lee, Richard E., Jr.

2007-01-01

In this activity, Namib and Antarctic arthropods are used to illustrate several important biological principles. Among these are the key ideas that form follows function and that the environment drives evolution. In addition, students will discover that the climates of the Namib Desert and the Antarctic Peninsula are similar in several ways, and…

Lipid fatty acid profile analyses in liver and serum in rats with nonalcoholic steatohepatitis using improved gas chromatography-mass spectrometry methodology

USDA-ARS?s Scientific Manuscript database

Fatty acids (FA) are essential components of lipids and exhibit important biological functions. The analyses of FAs are routinely carried out by gas chromatography-mass spectrometry, after multi-step sample preparation. In this study, several key experimental factors were carefully examined, validat...

How Animal Models Inform Child and Adolescent Psychiatry

PubMed Central

Stevens, Hanna E.; Vaccarino, Flora M.

2015-01-01

Objective Every available approach should be utilized to advance the field of child and adolescent psychiatry. Biological systems are important for the behavioral problems of children. Close examination of non-human animals and the biology and behavior they share with humans is an approach that must be used to advance the clinical work of child psychiatry. Method We review here how model systems are used to contribute to significant insights into childhood psychiatric disorders. Model systems have not only demonstrated causality of risk factors for psychiatric pathophysiology but have also allowed child psychiatrists to think in different ways about risks for psychiatric disorders and multiple levels that might be the basis of recovery and prevention. Results We present examples of how animal systems are utilized to benefit child psychiatry, including through environmental, genetic, and acute biological manipulations. Animal model work has been essential in our current thinking about childhood disorders, including the importance of dose and timing of risk factors, specific features of risk factors that are significant, neurochemistry involved in brain functioning, molecular components of brain development, and the importance of cellular processes previously neglected in psychiatric theories. Conclusion Animal models have clear advantages and disadvantages that must both be considered for these systems to be useful. Coupled with increasingly sophisticated methods for investigating human behavior and biology, animal model systems will continue to make essential contributions to our field. PMID:25901771

Studying Biological Rhythms of Person's Skin-galvanic Reaction and Dynamics of Light Transmission by Isomeric Substance in Space Flight Conditions

NASA Technical Reports Server (NTRS)

Glushko, Vladimir

2004-01-01

Intensity and amplitude of human functional systems and human most important organs are wavelike, rhythmic by nature. These waves have constant periodicity, phase and amplitude. The mentioned characteristics can vary, however their variations have a pronounced reiteration in the course of time. This indicates a hashing of several wave processes and their interference. Stochastic changes in wave processes characteristics of a human organism are explained either by 'pulsations' associated with hashing (superposition) of several wave processes and their interference, or by single influence of environmental physical factors on a human organism. Human beings have respectively periods of higher and lower efficiency, state of health and so on, depending not only of environmental factors, but also of 'internal' rhythmic factor. Sometimes peaks and falls periodicity of some or other characteristics is broken. Disturbance of steady-state biological rhythms is usually accompanied by reduction of activity steadiness of the most important systems of a human organism. In its turn this has an effect on organism's adaptation to changing living conditions as well as on general condition and efficiency of a human being. The latter factor is very important for space medicine. Biological rhythmology is a special branch of biology and medicine, it studies rhythmic activity mechanisms of organs, their systems, individuals and species. Appropriate researches were also carried out in space medicine.

PTMScout, a Web Resource for Analysis of High Throughput Post-translational Proteomics Studies*

PubMed Central

Naegle, Kristen M.; Gymrek, Melissa; Joughin, Brian A.; Wagner, Joel P.; Welsch, Roy E.; Yaffe, Michael B.; Lauffenburger, Douglas A.; White, Forest M.

2010-01-01

The rate of discovery of post-translational modification (PTM) sites is increasing rapidly and is significantly outpacing our biological understanding of the function and regulation of those modifications. To help meet this challenge, we have created PTMScout, a web-based interface for viewing, manipulating, and analyzing high throughput experimental measurements of PTMs in an effort to facilitate biological understanding of protein modifications in signaling networks. PTMScout is constructed around a custom database of PTM experiments and contains information from external protein and post-translational resources, including gene ontology annotations, Pfam domains, and Scansite predictions of kinase and phosphopeptide binding domain interactions. PTMScout functionality comprises data set comparison tools, data set summary views, and tools for protein assignments of peptides identified by mass spectrometry. Analysis tools in PTMScout focus on informed subset selection via common criteria and on automated hypothesis generation through subset labeling derived from identification of statistically significant enrichment of other annotations in the experiment. Subset selection can be applied through the PTMScout flexible query interface available for quantitative data measurements and data annotations as well as an interface for importing data set groupings by external means, such as unsupervised learning. We exemplify the various functions of PTMScout in application to data sets that contain relative quantitative measurements as well as data sets lacking quantitative measurements, producing a set of interesting biological hypotheses. PTMScout is designed to be a widely accessible tool, enabling generation of multiple types of biological hypotheses from high throughput PTM experiments and advancing functional assignment of novel PTM sites. PTMScout is available at http://ptmscout.mit.edu. PMID:20631208

Hands-on-Entropy, Energy Balance with Biological Relevance

NASA Astrophysics Data System (ADS)

Reeves, Mark

2015-03-01

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

Thermodynamic characterization of the multivalent interactions underlying rapid and selective translocation through the nuclear pore complex

PubMed Central

Hayama, Ryo; Sparks, Samuel; Hecht, Lee M.; Dutta, Kaushik; Karp, Jerome M.; Cabana, Christina M.; Rout, Michael P.; Cowburn, David

2018-01-01

Intrinsically disordered proteins (IDPs) play important roles in many biological systems. Given the vast conformational space that IDPs can explore, the thermodynamics of the interactions with their partners is closely linked to their biological functions. Intrinsically disordered regions of Phe–Gly nucleoporins (FG Nups) that contain multiple phenylalanine–glycine repeats are of particular interest, as their interactions with transport factors (TFs) underlie the paradoxically rapid yet also highly selective transport of macromolecules mediated by the nuclear pore complex. Here, we used NMR and isothermal titration calorimetry to thermodynamically characterize these multivalent interactions. These analyses revealed that a combination of low per-FG motif affinity and the enthalpy–entropy balance prevents high-avidity interaction between FG Nups and TFs, whereas the large number of FG motifs promotes frequent FG–TF contacts, resulting in enhanced selectivity. Our thermodynamic model underlines the importance of functional disorder of FG Nups. It helps explain the rapid and selective translocation of TFs through the nuclear pore complex and further expands our understanding of the mechanisms of “fuzzy” interactions involving IDPs. PMID:29374059

Biochemistry and Molecular Biology of Flaviviruses.

PubMed

Barrows, Nicholas J; Campos, Rafael K; Liao, Kuo-Chieh; Prasanth, K Reddisiva; Soto-Acosta, Ruben; Yeh, Shih-Chia; Schott-Lerner, Geraldine; Pompon, Julien; Sessions, October M; Bradrick, Shelton S; Garcia-Blanco, Mariano A

2018-04-25

Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that sicken a staggeringly high number of humans every year. Most of these pathogens are transmitted by mosquitos, and not surprisingly, as the earth warms and human populations grow and move, their geographic reach is increasing. Flaviviruses are simple RNA-protein machines that carry out protein synthesis, genome replication, and virion packaging in close association with cellular lipid membranes. In this review, we examine the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors. The latter are functionally divided into pro-viral and antiviral factors, both of which, not surprisingly, include many RNA binding proteins. In the interface between the virus and the hosts we highlight the role of a noncoding RNA produced by flaviviruses to impair antiviral host immune responses. Throughout the review, we highlight areas of intense investigation, or a need for it, and potential targets and tools to consider in the important battle against pathogenic flaviviruses.

Rhodamine-based fluorescent probe for direct bio-imaging of lysosomal pH changes.

PubMed

Shi, Xue-Lin; Mao, Guo-Jiang; Zhang, Xiao-Bing; Liu, Hong-Wen; Gong, Yi-Jun; Wu, Yong-Xiang; Zhou, Li-Yi; Zhang, Jing; Tan, Weihong

2014-12-01

Intracellular pH plays a pivotal role in various biological processes. In eukaryotic cells, lysosomes contain numerous enzymes and proteins exhibiting a variety of activities and functions at acidic pH (4.5-5.5), and abnormal variation in the lysosomal pH causes defects in lysosomal function. Thus, it is important to investigate lysosomal pH in living cells to understand its physiological and pathological processes. In this work, we designed a one-step synthesized rhodamine derivative (RM) with morpholine as a lysosomes tracker, to detect lysosomal pH changes with high sensitivity, high selectivity, high photostability and low cytotoxicity. The probe RM shows a 140-fold fluorescence enhancement over a pH range from 7.4 to 4.5 with a pKa value of 5.23. Importantly, RM can detect the chloroquine-induced lysosomal pH increase and monitor the dexamethasone-induced lysosomal pH changes during apoptosis in live cells. All these features demonstrate its value of practical application in biological systems. Copyright © 2014 Elsevier B.V. All rights reserved.

Computational study of stability of an H-H-type pseudoknot motif.

PubMed

Wang, Jun; Zhao, Yunjie; Wang, Jian; Xiao, Yi

2015-12-01

Motifs in RNA tertiary structures are important to their structural organizations and biological functions. Here we consider an H-H-type pseudoknot (HHpk) motif that consists of two hairpins connected by a junction loop and with kissing interactions between the two hairpin loops. Such a tertiary structural motif is recurrently found in RNA tertiary structures, but is difficult to predict computationally. So it is important to understand the mechanism of its formation and stability. Here we investigate the stability of the HHpk tertiary structure by using an all-atom molecular dynamics simulation. The results indicate that the HHpk tertiary structure is stable. However, it is found that this stability is not due to the helix-helix packing, as is usually expected, but is maintained by the combined action of the kissing hairpin loops and junctions, although the former plays the main role. Stable HHpk motifs may form structural platforms for the molecules to realize their biological functions. These results are useful for understanding the construction principle of RNA tertiary structures and structure prediction.

Proteases for Processing Proneuropeptides into Peptide Neurotransmitters and Hormones

PubMed Central

Hook, Vivian; Funkelstein, Lydiane; Lu, Douglas; Bark, Steven; Wegrzyn, Jill; Hwang, Shin-Rong

2009-01-01

Peptide neurotransmitters and peptide hormones, collectively known as neuropeptides, are required for cell-cell communication in neurotransmission and for regulation of endocrine functions. Neuropeptides are synthesized from protein precursors (termed proneuropeptides or prohormones) that require proteolytic processing primarily within secretory vesicles that store and secrete the mature neuropeptides to control target cellular and organ systems. This review describes interdisciplinary strategies that have elucidated two primary protease pathways for prohormone processing consisting of the cysteine protease pathway mediated by secretory vesicle cathepsin L and the well-known subtilisin-like proprotein convertase pathway that together support neuropeptide biosynthesis. Importantly, this review discusses important areas of current and future biomedical neuropeptide research with respect to biological regulation, inhibitors, structural features of proneuropeptide and protease interactions, and peptidomics combined with proteomics for systems biological approaches. Future studies that gain in-depth understanding of protease mechanisms for generating active neuropeptides will be instrumental for translational research to develop pharmacological strategies for regulation of neuropeptide functions. Pharmacological applications for neuropeptide research may provide valuable therapeutics in health and disease. PMID:18184105

Interactions among ecosystem stressors and their importance in conservation

PubMed Central

Darling, Emily S.; Brown, Christopher J.

2016-01-01

Interactions between multiple ecosystem stressors are expected to jeopardize biological processes, functions and biodiversity. The scientific community has declared stressor interactions—notably synergies—a key issue for conservation and management. Here, we review ecological literature over the past four decades to evaluate trends in the reporting of ecological interactions (synergies, antagonisms and additive effects) and highlight the implications and importance to conservation. Despite increasing popularity, and ever-finer terminologies, we find that synergies are (still) not the most prevalent type of interaction, and that conservation practitioners need to appreciate and manage for all interaction outcomes, including antagonistic and additive effects. However, it will not be possible to identify the effect of every interaction on every organism's physiology and every ecosystem function because the number of stressors, and their potential interactions, are growing rapidly. Predicting the type of interactions may be possible in the near-future, using meta-analyses, conservation-oriented experiments and adaptive monitoring. Pending a general framework for predicting interactions, conservation management should enact interventions that are robust to uncertainty in interaction type and that continue to bolster biological resilience in a stressful world. PMID:26865306

Rational design of gold nanocarrier for the delivery of JAG-1 peptide.

PubMed

Matea, Cristian T; Mocan, Teodora; Tabaran, Flaviu; Iancu, Cornel; Mocan, Lucian-Constantin

2015-06-16

Unique properties exhibited by nanoparticles makes them great candidates for applications in physics, chemistry, biology, material science and medicine. The biological applications of water-soluble gold nanoparticles range from contrast agents, delivery vehicles to therapeutics. Notch signaling is a complex network that orchestrates cell fate decisions, which involves proliferation, migration, differentiation and cell death in organisms ranging from insects to humans. Studies have showed that a correct orientation of the Jag-1 signalling protein on the substrates proves to be of great importance when promoting Jagged-1 Notch interactions, also the availability of the ligands, super cedes the importance of their concentration. The aim of the present study was to synthetize a Jag-1 functionalized nanocarrier, which would promote an efficient interaction between the Jag-1 peptide and the Notch receptor. To this end, two routes for gold nanoparticle-peptide assembly were investigated, and the synthetized bio-nanostructures were characterized and compared by means of UV-Vis, FT-IR, DLS and AFM techniques. We have obtained a stable, monodisperse, hetero-functionalized GNP-PEG-JAG-1 bio-nanostructure for Notch pathway activation applications.

Fluorescent Probes Used for Detection of Hydrogen Peroxide under Biological Conditions.

PubMed

Żamojć, Krzysztof; Zdrowowicz, Magdalena; Jacewicz, Dagmara; Wyrzykowski, Dariusz; Chmurzyński, Lech

2016-05-03

Hydrogen peroxide is a well-established precursor of reactive oxygen and nitrogen species that are known to contribute to oxidative stress-the crucial factor responsible for the course of a wide range of phy-sicochemical processes as well as the genesis of various diseases, such as cancer and neurodegenerative disorders. Thus, the development of sensitive and selective methods for the detection and quantitative determination of hydrogen peroxide is of great importance in monitoring the in vivo production of that species and elucidating its biological functions. This review highlights the progress that has been made in the development of fluorescent and luminescent probes (excluding nanoparticles) employed to monitor hydrogen peroxide under biological conditions. Attention was focused on probes developed in the past 10 years.

Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges.

PubMed

Ha, Dinh; Yang, Ningning; Nadithe, Venkatareddy

2016-07-01

Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body׳s own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed.

Pharmacological activities of a new glycosaminoglycan, acharan sulfate isolated from the giant African snail Achatina fulica.

PubMed

Shim, Jin Young; Lee, Yeon Sil; Jung, Sang Hoon; Choi, Hyung Seok; Shin, Kuk Hyun; Kim, Yeong Shik

2002-12-01

Acharan sulfate (AS) is a glycosaminoglycan (GAG) prepared from the giant African snail, Achatina fulica. In this study, some biological activities of AS were evaluated on the basis of structural similarities to heparin/heparan sulfate and the biological functions of GAGs. We demonstrated that it exhibited strong immunostimulating activities as measured by carbon clearance test in mice and in vivo phagocytosis. It also exhibited a significant hypoglycemic activity in epinephrine (EP)-induced hyperglycemia as well as antifatigue effects by weight-loaded forced swimming test. And it showed hypolipidemic activities in cholesterol-rich mixture induced hyperlipidemia in rats. The above results indicate that AS has diverse biological activities and suggest therapeutically important target molecules.

A machine learning approach to predicting protein-ligand binding affinity with applications to molecular docking.

PubMed

Ballester, Pedro J; Mitchell, John B O

2010-05-01

Accurately predicting the binding affinities of large sets of diverse protein-ligand complexes is an extremely challenging task. The scoring functions that attempt such computational prediction are essential for analysing the outputs of molecular docking, which in turn is an important technique for drug discovery, chemical biology and structural biology. Each scoring function assumes a predetermined theory-inspired functional form for the relationship between the variables that characterize the complex, which also include parameters fitted to experimental or simulation data and its predicted binding affinity. The inherent problem of this rigid approach is that it leads to poor predictivity for those complexes that do not conform to the modelling assumptions. Moreover, resampling strategies, such as cross-validation or bootstrapping, are still not systematically used to guard against the overfitting of calibration data in parameter estimation for scoring functions. We propose a novel scoring function (RF-Score) that circumvents the need for problematic modelling assumptions via non-parametric machine learning. In particular, Random Forest was used to implicitly capture binding effects that are hard to model explicitly. RF-Score is compared with the state of the art on the demanding PDBbind benchmark. Results show that RF-Score is a very competitive scoring function. Importantly, RF-Score's performance was shown to improve dramatically with training set size and hence the future availability of more high-quality structural and interaction data is expected to lead to improved versions of RF-Score. pedro.ballester@ebi.ac.uk; jbom@st-andrews.ac.uk Supplementary data are available at Bioinformatics online.

Evolution, functional differentiation, and co-expression of the RLK gene family revealed in Jilin ginseng, Panax ginseng C.A. Meyer.

PubMed

Lin, Yanping; Wang, Kangyu; Li, Xiangyu; Sun, Chunyu; Yin, Rui; Wang, Yanfang; Wang, Yi; Zhang, Meiping

2018-02-21

Most genes in a genome exist in the form of a gene family; therefore, it is necessary to have knowledge of how a gene family functions to comprehensively understand organismal biology. The receptor-like kinase (RLK)-encoding gene family is one of the most important gene families in plants. It plays important roles in biotic and abiotic stress tolerances, and growth and development. However, little is known about the functional differentiation and relationships among the gene members within a gene family in plants. This study has isolated 563 RLK genes (designated as PgRLK genes) expressed in Jilin ginseng (Panax ginseng C.A. Meyer), investigated their evolution, and deciphered their functional diversification and relationships. The PgRLK gene family is highly diverged and formed into eight types. The LRR type is the earliest and most prevalent, while only the Lec type originated after P. ginseng evolved. Furthermore, although the members of the PgRLK gene family all encode receptor-like protein kinases and share conservative domains, they are functionally very diverse, participating in numerous biological processes. The expressions of different members of the PgRLK gene family are extremely variable within a tissue, at a developmental stage and in the same cultivar, but most of the genes tend to express correlatively, forming a co-expression network. These results not only provide a deeper and comprehensive understanding of the evolution, functional differentiation and correlation of a gene family in plants, but also an RLK genic resource useful for enhanced ginseng genetic improvement.

The roles of Microphthalmia Transcription Factor and pigmentation in melanoma

PubMed Central

Hsiao, Jennifer J; Fisher, David E

2014-01-01

MITF and pigmentation play important roles in both normal melanocyte and transformed melanoma cell biology. MITF is regulated by many pathways and it also regulates many targets, some of which are still being discovered and functionally validated. MITF is involved in a wide range of processes in melanocytes, including pigment synthesis and lineage survival. Pigmentation itself plays an important role as the interface between genetic and environmental factors that contribute to melanoma. PMID:25111671

Lycopene metabolism and its biological significance12345

PubMed Central

2012-01-01

The beneficial effects of a high intake of tomatoes and tomato products on the risk of certain chronic diseases have been presented in many epidemiologic studies, with the suggestion that lycopene (a major carotenoid in tomatoes) is a micronutrient with important health benefits. Within the past few years, we have gained greater knowledge of the metabolism of lycopene and the biological effects of lycopene derivatives. In particular, the characterization and study of β-carotene 9′,10′-oxygenase has shown that this enzyme can catalyze the excentric cleavage of both provitamin and non–provitamin A carotenoids to form apo-10′-carotenoids, including apo-10′-lycopenoids from lycopene. This raised an important question of whether the effect of lycopene on various cellular functions and signaling pathways is a result of the direct actions of intact lycopene or its derivatives. Several reports, including our own, support the notion that the biological activities of lycopene can be mediated by apo-10′-lycopenoids. More research is clearly needed to identify and characterize additional lycopene metabolites and their biological activities, which will potentially provide invaluable insights into the mechanisms underlying the effects of lycopene in humans. PMID:23053559

Cytomics - importance of multimodal analysis of cell function and proliferation in oncology.

PubMed

Tárnok, A; Bocsi, J; Brockhoff, G

2006-12-01

Cancer is a highly complex and heterogeneous disease involving a succession of genetic changes (frequently caused or accompanied by exogenous trauma), and resulting in a molecular phenotype that in turn results in a malignant specification. The development of malignancy has been described as a multistep process involving self-sufficiency in growth signals, insensitivity to antigrowth signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and finally tissue invasion and metastasis. The quantitative analysis of networking molecules within the cells might be applied to understand native-state tissue signalling biology, complex drug actions and dysfunctional signalling in transformed cells, that is, in cancer cells. High-content and high-throughput single-cell analysis can lead to systems biology and cytomics. The application of cytomics in cancer research and diagnostics is very broad, ranging from the better understanding of the tumour cell biology to the identification of residual tumour cells after treatment, to drug discovery. The ultimate goal is to pinpoint in detail these processes on the molecular, cellular and tissue level. A comprehensive knowledge of these will require tissue analysis, which is multiplex and functional; thus, vast amounts of data are being collected from current genomic and proteomic platforms for integration and interpretation as well as for new varieties of updated cytomics technology. This overview will briefly highlight the most important aspects of this continuously developing field.

The hydroxyl-functionalized magnetic particles for purification of glycan-binding proteins.

PubMed

Sun, Xiuxuan; Yang, Ganglong; Sun, Shisheng; Quan, Rui; Dai, Weiwei; Li, Bin; Chen, Chao; Li, Zheng

2009-12-01

Glycan-protein interactions play important biological roles in biological processes. Although there are some methods such as glycan arrays that may elucidate recognition events between carbohydrates and protein as well as screen the important glycan-binding proteins, there is a lack of simple effectively separate method to purify them from complex samples. In proteomics studies, fractionation of samples can help to reduce their complexity and to enrich specific classes of proteins for subsequent downstream analyses. Herein, a rapid simple method for purification of glycan-binding proteins from proteomic samples was developed using hydroxyl-coated magnetic particles coupled with underivatized carbohydrate. Firstly, the epoxy-coated magnetic particles were further hydroxyl functionalized with 4-hydroxybenzhydrazide, then the carbohydrates were efficiently immobilized on hydroxyl functionalized surface of magnetic particles by formation of glycosidic bond with the hemiacetal group at the reducing end of the suitable carbohydrates via condensation. All conditions of this method were optimized. The magnetic particle-carbohydrate conjugates were used to purify the glycan-binding proteins from human serum. The fractionated glycan-binding protein population was displayed by SDS-PAGE. The result showed that the amount of 1 mg magnetic particles coupled with mannose in acetate buffer (pH 5.4) was 10 micromol. The fractionated glycan-binding protein population in human serum could be eluted from the magnetic particle-mannose conjugates by 0.1% SDS. The methodology could work together with the glycan microarrays for screening and purification of the important GBPs from complex protein samples.

Functional Abstraction as a Method to Discover Knowledge in Gene Ontologies

PubMed Central

Ultsch, Alfred; Lötsch, Jörn

2014-01-01

Computational analyses of functions of gene sets obtained in microarray analyses or by topical database searches are increasingly important in biology. To understand their functions, the sets are usually mapped to Gene Ontology knowledge bases by means of over-representation analysis (ORA). Its result represents the specific knowledge of the functionality of the gene set. However, the specific ontology typically consists of many terms and relationships, hindering the understanding of the ‘main story’. We developed a methodology to identify a comprehensibly small number of GO terms as “headlines” of the specific ontology allowing to understand all central aspects of the roles of the involved genes. The Functional Abstraction method finds a set of headlines that is specific enough to cover all details of a specific ontology and is abstract enough for human comprehension. This method exceeds the classical approaches at ORA abstraction and by focusing on information rather than decorrelation of GO terms, it directly targets human comprehension. Functional abstraction provides, with a maximum of certainty, information value, coverage and conciseness, a representation of the biological functions in a gene set plays a role. This is the necessary means to interpret complex Gene Ontology results thus strengthening the role of functional genomics in biomarker and drug discovery. PMID:24587272

Influence of Different ECM-Like Hydrogels on Neurite Outgrowth Induced by Adipose Tissue-Derived Stem Cells

PubMed Central

Oliveira, E.; Assunção-Silva, R. C.; Teixeira, F. G.

2017-01-01

Mesenchymal stem cells (MSCs) have been proposed for spinal cord injury (SCI) applications due to their capacity to secrete growth factors and vesicles—secretome—that impacts important phenomena in SCI regeneration. To improve MSC survival into SCI sites, hydrogels have been used as transplantation vehicles. Herein, we hypothesized if different hydrogels could interact differently with adipose tissue-derived MSCs (ASCs). The efficacy of three natural hydrogels, gellan gum (functionalized with a fibronectin peptide), collagen, and a hydrogel rich in laminin epitopes (NVR-gel) in promoting neuritogenesis (alone and cocultured with ASCs), was evaluated in the present study. Their impact on ASC survival, metabolic activity, and gene expression was also evaluated. Our results indicated that all hydrogels supported ASC survival and viability, being this more evident for the functionalized GG hydrogels. Moreover, the presence of different ECM-derived biological cues within the hydrogels appears to differently affect the mRNA levels of growth factors involved in neuronal survival, differentiation, and axonal outgrowth. All the hydrogel-based systems supported axonal growth mediated by ASCs, but this effect was more robust in functionalized GG. The data herein presented highlights the importance of biological cues within hydrogel-based biomaterials as possible modulators of ASC secretome and its effects for SCI applications. PMID:29333166

Structural insights into the functional versatility of WW domain-containing oxidoreductase tumor suppressor.

PubMed

Farooq, Amjad

2015-03-01

Recent work on WW domain-containing oxidoreductase (WWOX) tumor suppressor is beginning to shed new light on both the molecular mechanism of action of its WW domains as well as the contiguous catalytic domain. Herein, the structural basis underlying the ability of WW1 domain to bind to various physiological ligands and how the orphan WW2 tandem partner synergizes its ligand binding in the context of WW1-WW2 tandem module of WWOX is discussed. Notably, the WW domains within the WW1-WW2 tandem module physically associate so as to adopt a fixed spatial orientation relative to each other. In this manner, the association of WW2 domain with WW1 hinders ligand binding to the latter. Consequently, ligand binding to WW1 domain not only results in the displacement of WW2 lid but also disrupts the fixed orientation of WW domains in the liganded conformation. Equally importantly, structure-guided functional approach suggests that the catalytic domain of WWOX likely serves as a retinal oxidoreductase that catalyzes the reversible oxidation and reduction of all-trans-retinal. Collectively, this review provides structural insights into the functional versatility of a key signaling protein with important implications on its biology. © 2015 by the Society for Experimental Biology and Medicine.

Neuromuscular Junction Formation between Human Stem cell-derived Motoneurons and Human Skeletal Muscle in a Defined System

PubMed Central

Guo, Xiufang; Gonzalez, Mercedes; Stancescu, Maria; Vandenburgh, Herman; Hickman, James

2011-01-01

Functional in vitro models composed of human cells will constitute an important platform in the next generation of system biology and drug discovery. This study reports a novel human-based in vitro Neuromuscular Junction (NMJ) system developed in a defined serum-free medium and on a patternable non-biological surface. The motoneurons and skeletal muscles were derived from fetal spinal stem cells and skeletal muscle stem cells. The motoneurons and skeletal myotubes were completely differentiated in the co-culture based on morphological analysis and electrophysiology. NMJ formation was demonstrated by phase contrast microscopy, immunocytochemistry and the observation of motoneuron-induced muscle contractions utilizing time lapse recordings and their subsequent quenching by D-Tubocurarine. Generally, functional human based systems would eliminate the issue of species variability during the drug development process and its derivation from stem cells bypasses the restrictions inherent with utilization of primary human tissue. This defined human-based NMJ system is one of the first steps in creating functional in vitro systems and will play an important role in understanding NMJ development, in developing high information content drug screens and as test beds in preclinical studies for spinal or muscular diseases/injuries such as muscular dystrophy, Amyotrophic lateral sclerosis and spinal cord repair. PMID:21944471

Neuromuscular junction formation between human stem cell-derived motoneurons and human skeletal muscle in a defined system.

PubMed

Guo, Xiufang; Gonzalez, Mercedes; Stancescu, Maria; Vandenburgh, Herman H; Hickman, James J

2011-12-01

Functional in vitro models composed of human cells will constitute an important platform in the next generation of system biology and drug discovery. This study reports a novel human-based in vitro Neuromuscular Junction (NMJ) system developed in a defined serum-free medium and on a patternable non-biological surface. The motoneurons and skeletal muscles were derived from fetal spinal stem cells and skeletal muscle stem cells. The motoneurons and skeletal myotubes were completely differentiated in the co-culture based on morphological analysis and electrophysiology. NMJ formation was demonstrated by phase contrast microscopy, immunocytochemistry and the observation of motoneuron-induced muscle contractions utilizing time-lapse recordings and their subsequent quenching by d-Tubocurarine. Generally, functional human based systems would eliminate the issue of species variability during the drug development process and its derivation from stem cells bypasses the restrictions inherent with utilization of primary human tissue. This defined human-based NMJ system is one of the first steps in creating functional in vitro systems and will play an important role in understanding NMJ development, in developing high information content drug screens and as test beds in preclinical studies for spinal or muscular diseases/injuries such as muscular dystrophy, Amyotrophic lateral sclerosis and spinal cord repair. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed Central

McDougall, Carmel; Woodcroft, Ben J.

2016-01-01

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 construction of biological materials with diverse morphologies. The SilkSlider predictor software developed here is available at https://github.com/wwood/SilkSlider. PMID:27415783

Aquaporin structure-function relationships: water flow through plant living cells.

PubMed

Zhao, Chang-Xing; Shao, Hong-Bo; Chu, Li-Ye

2008-04-01

Plant aquaporins play an important role in water uptake and movement-an aquaporin that opens and closes a gate that regulates water movement in and out of cells. Some plant aquaporins also play an important role in response to water stress. Since their discovery, advancing knowledge of their structures and properties led to an understanding of the basic features of the water transport mechanism and increased illumination to water relations. Meanwhile, molecular and functional characterization of aquaporins has revealed the significance of their regulation in response to the adverse environments such as salinity and drought. This paper reviews the structure, species diversity, physiology function, regulation of plant aquaporins, and the relations between environmental factors and plant aquaporins. Complete understanding of aquaporin function and regulation is to integrate those mechanisms in time and space and to well regulate the permeation of water across biological membranes under changing environmental and developmental conditions.

Intermediates of Metabolism: From Bystanders to Signalling Molecules.

PubMed

Haas, Robert; Cucchi, Danilo; Smith, Joanne; Pucino, Valentina; Macdougall, Claire Elizabeth; Mauro, Claudio

2016-05-01

The integration of biochemistry into immune cell biology has contributed immensely to our understanding of immune cell function and the associated pathologies. So far, most studies have focused on the regulation of metabolic pathways during an immune response and their contribution to its success. More recently, novel signalling functions of metabolic intermediates are being discovered that might play important roles in the regulation of immunity. Here we describe the three long-known small metabolites lactate, acetyl-CoA, and succinate in the context of immunometabolic signalling. Functions of these ubiquitous molecules are largely dependent on their intra- and extracellular concentrations as well as their subcompartmental localisation. Importantly, the signalling functions of these metabolic intermediates extend beyond self-regulatory roles and include cell-to-cell communication and sensing of microenvironmental conditions to elicit stress responses and cellular adaptation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Form follows function: the importance of endoplasmic reticulum shape.

PubMed

Westrate, L M; Lee, J E; Prinz, W A; Voeltz, G K

2015-01-01

The endoplasmic reticulum (ER) has a remarkably complex structure, composed of a single bilayer that forms the nuclear envelope, along with a network of sheets and dynamic tubules. Our understanding of the biological significance of the complex architecture of the ER has improved dramatically in the last few years. The identification of proteins and forces required for maintaining ER shape, as well as more advanced imaging techniques, has allowed the relationship between ER shape and function to come into focus. These studies have also revealed unexpected new functions of the ER and novel ER domains regulating alterations in ER dynamics. The importance of ER structure has become evident as recent research has identified diseases linked to mutations in ER-shaping proteins. In this review, we discuss what is known about the maintenance of ER architecture, the relationship between ER structure and function, and diseases associated with defects in ER structure.

Synthetic Biology: Putting Synthesis into Biology

PubMed Central

Liang, Jing; Luo, Yunzi; Zhao, Huimin

2010-01-01

The ability to manipulate living organisms is at the heart of a range of emerging technologies that serve to address important and current problems in environment, energy, and health. However, with all its complexity and interconnectivity, biology has for many years been recalcitrant to engineering manipulations. The recent advances in synthesis, analysis, and modeling methods have finally provided the tools necessary to manipulate living systems in meaningful ways, and have led to the coining of a field named synthetic biology. The scope of synthetic biology is as complicated as life itself – encompassing many branches of science, and across many scales of application. New DNA synthesis and assembly techniques have made routine the customization of very large DNA molecules. This in turn has allowed the incorporation of multiple genes and pathways. By coupling these with techniques that allow for the modeling and design of protein functions, scientists have now gained the tools to create completely novel biological machineries. Even the ultimate biological machinery – a self-replicating organism – is being pursued at this moment. It is the purpose of this review to dissect and organize these various components of synthetic biology into a coherent picture. PMID:21064036

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

PubMed

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

2017-10-01

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

RanBPM (RanBP9) regulates mouse c-Kit receptor level and is essential for normal development of bone marrow progenitor cells

PubMed Central

Singh, Satyendra; Klarmann, Kimberly D.; Coppola, Vincenzo; Keller, Jonathan R.; Tessarollo, Lino

2016-01-01

c-Kit is a tyrosine kinase receptor important for gametogenesis, hematopoiesis, melanogenesis and mast cell biology. Dysregulation of c-Kit function is oncogenic and its expression in the stem cell niche of a number of tissues has underlined its relevance for regenerative medicine and hematopoietic stem cell biology. Yet, very little is known about the mechanisms that control c-Kit protein levels. Here we show that the RanBPM/RanBP9 scaffold protein binds to c-Kit and is necessary for normal c-Kit protein expression in the mouse testis and subset lineages of the hematopoietic system. RanBPM deletion causes a reduction in c-Kit protein but not its mRNA suggesting a posttranslational mechanism. This regulation is specific to the c-Kit receptor since RanBPM reduction does not affect other membrane proteins examined. Importantly, in both mouse hematopoietic system and testis, RanBPM deficiency causes defects consistent with c-Kit loss of expression suggesting that RanBPM is an important regulator of c-Kit function. The finding that this regulatory mechanism is also present in human cells expressing endogenous RanBPM and c-Kit suggests a potential new strategy to target oncogenic c-Kit in malignancies. PMID:27835883

RanBPM (RanBP9) regulates mouse c-Kit receptor level and is essential for normal development of bone marrow progenitor cells.

PubMed

Puverel, Sandrine; Kiris, Erkan; Singh, Satyendra; Klarmann, Kimberly D; Coppola, Vincenzo; Keller, Jonathan R; Tessarollo, Lino

2016-12-20

c-Kit is a tyrosine kinase receptor important for gametogenesis, hematopoiesis, melanogenesis and mast cell biology. Dysregulation of c-Kit function is oncogenic and its expression in the stem cell niche of a number of tissues has underlined its relevance for regenerative medicine and hematopoietic stem cell biology. Yet, very little is known about the mechanisms that control c-Kit protein levels. Here we show that the RanBPM/RanBP9 scaffold protein binds to c-Kit and is necessary for normal c-Kit protein expression in the mouse testis and subset lineages of the hematopoietic system. RanBPM deletion causes a reduction in c-Kit protein but not its mRNA suggesting a posttranslational mechanism. This regulation is specific to the c-Kit receptor since RanBPM reduction does not affect other membrane proteins examined. Importantly, in both mouse hematopoietic system and testis, RanBPM deficiency causes defects consistent with c-Kit loss of expression suggesting that RanBPM is an important regulator of c-Kit function. The finding that this regulatory mechanism is also present in human cells expressing endogenous RanBPM and c-Kit suggests a potential new strategy to target oncogenic c-Kit in malignancies.

Wikidata as a semantic framework for the Gene Wiki initiative.

PubMed

Burgstaller-Muehlbacher, Sebastian; Waagmeester, Andra; Mitraka, Elvira; Turner, Julia; Putman, Tim; Leong, Justin; Naik, Chinmay; Pavlidis, Paul; Schriml, Lynn; Good, Benjamin M; Su, Andrew I

2016-01-01

Open biological data are distributed over many resources making them challenging to integrate, to update and to disseminate quickly. Wikidata is a growing, open community database which can serve this purpose and also provides tight integration with Wikipedia. In order to improve the state of biological data, facilitate data management and dissemination, we imported all human and mouse genes, and all human and mouse proteins into Wikidata. In total, 59,721 human genes and 73,355 mouse genes have been imported from NCBI and 27,306 human proteins and 16,728 mouse proteins have been imported from the Swissprot subset of UniProt. As Wikidata is open and can be edited by anybody, our corpus of imported data serves as the starting point for integration of further data by scientists, the Wikidata community and citizen scientists alike. The first use case for these data is to populate Wikipedia Gene Wiki infoboxes directly from Wikidata with the data integrated above. This enables immediate updates of the Gene Wiki infoboxes as soon as the data in Wikidata are modified. Although Gene Wiki pages are currently only on the English language version of Wikipedia, the multilingual nature of Wikidata allows for usage of the data we imported in all 280 different language Wikipedias. Apart from the Gene Wiki infobox use case, a SPARQL endpoint and exporting functionality to several standard formats (e.g. JSON, XML) enable use of the data by scientists. In summary, we created a fully open and extensible data resource for human and mouse molecular biology and biochemistry data. This resource enriches all the Wikipedias with structured information and serves as a new linking hub for the biological semantic web. Database URL: https://www.wikidata.org/. © The Author(s) 2016. Published by Oxford University Press.

The biological function of consciousness

PubMed Central

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

Mouse interleukin-2 structure-function studies: substitutions in the first alpha-helix can specifically inactivate p70 receptor binding and mutations in the fifth alpha-helix can specifically inactivate p55 receptor binding.

PubMed Central

Zurawski, S M; Zurawski, G

1989-01-01

The function of two alpha-helical regions of mouse interleukin-2 were analyzed by saturation substitution analysis. The functional parts of the first alpha-helix (A) was defined as residues 31-39 by the observation that proline substitutions within this region inactivate the protein. Four residues within alpha-helix A, Leu31, Asp34, Leu35 and Leu38, were found to be crucial for biological activity. Structural modeling suggested that these four residues are clustered on one face of alpha-helix A. Residues 31 and 35 had to remain hydrophobic for the molecule to be functional. At residue 38 there was a preference for hydrophobic side chain residues, while at residue 34 some small side chain residues as well as acidic or amide side chain residues were functionally acceptable. Inactivating changes at residue 34 had no effect upon the ability of the protein to interact with the p55 receptor. Disruption of the fifth alpha-helix (E), which had little effect upon biological activity, resulted in an inability of the protein to interact with the p55 receptor. Mutagenesis of the alpha-helix E region demonstrated that alpha-helicity and the nature of the side chain residues in this region were unimportant for biological activity. The region immediately proximal to alpha-helix E was important only for the single intramolecular disulfide linkage. PMID:2583124

Recent advances in designed coiled coils and helical bundles with inorganic prosthetic groups-from structural to functional applications.

PubMed

Peacock, Anna Fa

2016-04-01

Recent contributions to the de novo design of metalloproteins based on coiled coils and helical bundles are described herein, with examples covering mononuclear, multinuclear, and metallo-porphyrin sites, as well as membrane soluble designs. Important progress is being made in the field with a diverse range of functionalities, sometimes beyond those found in biology, being successfully engineered into these simplified scaffolds and represents an exciting prospect for the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

Site-3 sea anemone toxins: molecular probes of gating mechanisms in voltage-dependent sodium channels.

PubMed

Smith, Jaime J; Blumenthal, Kenneth M

2007-02-01

Sea anemone toxins, whose biological function is the capture of marine prey, are invaluable tools for studying the structure and function of mammalian voltage-gated sodium channels. Their high degree of specificity and selectivity have allowed for detailed analysis of inactivation gating and assignment of molecular entities responsible for this process. Because of their ability to discriminate among channel isoforms, and their high degree of structural conservation, these toxins could serve as important lead compounds for future pharmaceutical design.

Skeleton and Glucose Metabolism: A Bone-Pancreas Loop

PubMed Central

Luce, Vincenza; Ventura, Annamaria; Colucci, Silvia; Cavallo, Luciano; Grano, Maria

2015-01-01

Bone has been considered a structure essential for mobility, calcium homeostasis, and hematopoietic function. Recent advances in bone biology have highlighted the importance of skeleton as an endocrine organ which regulates some metabolic pathways, in particular, insulin signaling and glucose tolerance. This review will point out the role of bone as an endocrine “gland” and, specifically, of bone-specific proteins, as the osteocalcin (Ocn), and proteins involved in bone remodeling, as osteoprotegerin, in the regulation of insulin function and glucose metabolism. PMID:25873957

Lights, camera, actin.

PubMed

Rubenstein, Peter A; Wen, Kuo-Kuang

2005-10-01

Actin participates in many important biological processes. Currently, intensive investigation is being carried out in a number of laboratories concerning the function of actin in these processes and the molecular basis of its functions. We present a glimpse into four of these areas: actin-like proteins in bacterial cells, actin in the eukaryotic nucleus, the conformational plasticity of the actin filament, and finally, Arp2/3-dependent regulation of actin filament branching and creation of new filament barbed ends. IUBMB Life, 57: 683-687, 2005.

Imaging of gastroenteropancreatic neuroendocrine tumors

PubMed Central

Tan, Eik Hock; Tan, Cher Heng

2011-01-01

Imaging of gastroenteropancreatic neuroendocrine tumors can be broadly divided into anatomic and functional techniques. Anatomic imaging determines the local extent of the primary lesion, providing crucial information required for surgical planning. Functional imaging, not only determines the extent of metastatic disease spread, but also provides important information with regard to the biologic behavior of the tumor, allowing clinicians to decide on the most appropriate forms of treatment. We review the current literature on this subject, with emphasis on the strengths of each imaging modality. PMID:21603312

Rad5, HLTF, and SHPRH: A Fresh View of an Old Story.

PubMed

Elserafy, Menattallah; Abugable, Arwa A; Atteya, Reham; El-Khamisy, Sherif F

2018-05-25

Not only have helicase-like transcription factor (HLTF) and SNF2 histone-linker PHD-finger RING-finger helicase (SHPRH) proved to be important players in post-replication repair like their yeast counterpart, Rad5, but they are also involved in multiple biological functions and are associated with several human disorders. We provide here an updated view of their functions, associated diseases, and potential therapeutic approaches. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.