Sample records for advanced biochemical processes

  1. A review of digital microfluidics as portable platforms for lab-on a-chip applications.

    PubMed

    Samiei, Ehsan; Tabrizian, Maryam; Hoorfar, Mina

    2016-07-07

    Following the development of microfluidic systems, there has been a high tendency towards developing lab-on-a-chip devices for biochemical applications. A great deal of effort has been devoted to improve and advance these devices with the goal of performing complete sets of biochemical assays on the device and possibly developing portable platforms for point of care applications. Among the different microfluidic systems used for such a purpose, digital microfluidics (DMF) shows high flexibility and capability of performing multiplex and parallel biochemical operations, and hence, has been considered as a suitable candidate for lab-on-a-chip applications. In this review, we discuss the most recent advances in the DMF platforms, and evaluate the feasibility of developing multifunctional packages for performing complete sets of processes of biochemical assays, particularly for point-of-care applications. The progress in the development of DMF systems is reviewed from eight different aspects, including device fabrication, basic fluidic operations, automation, manipulation of biological samples, advanced operations, detection, biological applications, and finally, packaging and portability of the DMF devices. Success in developing the lab-on-a-chip DMF devices will be concluded based on the advances achieved in each of these aspects.

  2. Current Challenges in Plant Eco-Metabolomics

    PubMed Central

    Peters, Kristian; Worrich, Anja; Alka, Oliver; Balcke, Gerd; Bruelheide, Helge; Dietz, Sophie; Dührkop, Kai; Heinig, Uwe; Kücklich, Marlen; Müller, Caroline; Poeschl, Yvonne; Pohnert, Georg; Ruttkies, Christoph; Schweiger, Rabea; Shahaf, Nir; Tortosa, Maria; Ueberschaar, Nico; Velasco, Pablo; Weiß, Brigitte M.; van Dam, Nicole M.

    2018-01-01

    The relatively new research discipline of Eco-Metabolomics is the application of metabolomics techniques to ecology with the aim to characterise biochemical interactions of organisms across different spatial and temporal scales. Metabolomics is an untargeted biochemical approach to measure many thousands of metabolites in different species, including plants and animals. Changes in metabolite concentrations can provide mechanistic evidence for biochemical processes that are relevant at ecological scales. These include physiological, phenotypic and morphological responses of plants and communities to environmental changes and also interactions with other organisms. Traditionally, research in biochemistry and ecology comes from two different directions and is performed at distinct spatiotemporal scales. Biochemical studies most often focus on intrinsic processes in individuals at physiological and cellular scales. Generally, they take a bottom-up approach scaling up cellular processes from spatiotemporally fine to coarser scales. Ecological studies usually focus on extrinsic processes acting upon organisms at population and community scales and typically study top-down and bottom-up processes in combination. Eco-Metabolomics is a transdisciplinary research discipline that links biochemistry and ecology and connects the distinct spatiotemporal scales. In this review, we focus on approaches to study chemical and biochemical interactions of plants at various ecological levels, mainly plant–organismal interactions, and discuss related examples from other domains. We present recent developments and highlight advancements in Eco-Metabolomics over the last decade from various angles. We further address the five key challenges: (1) complex experimental designs and large variation of metabolite profiles; (2) feature extraction; (3) metabolite identification; (4) statistical analyses; and (5) bioinformatics software tools and workflows. The presented solutions to these challenges will advance connecting the distinct spatiotemporal scales and bridging biochemistry and ecology. PMID:29734799

  3. Effects of stress on endocrine and metabolic processes and redirection: Crosstalk between subcellular compartments

    USDA-ARS?s Scientific Manuscript database

    Recent advances in genome analysis and biochemical pathway mapping have advanced our understanding of how biological systems have evolved over time. Protein and DNA marker comparisons suggest that several of these systems are both ancient in origin but highly conserved into today’s evolved species. ...

  4. Effects of advanced treatment of municipal wastewater on the White River near Indianapolis, Indiana; trends in water quality, 1978-86

    USGS Publications Warehouse

    Crawford, Charles G.; Wangsness, David J.

    1993-01-01

    The City of Indianapolis has constructed state-of-the-art advanced municipal wastewater-treatment systems to enlarge and upgrade the existing secondary-treatment processes at its Belmont and Southport treatment plants. These new advanced-wastewater-treatment plants became operational in 1983. A nonparametric statistical procedure--a modified form of the Wilcoxon-Mann-Whitney rank-sum test--was used to test for trends in time-series water-quality data from four sites on the White River and from the Belmont and Southport wastewater-treatment plants. Time-series data representative of pre-advanced- (1978-1980) and post-advanced- (1983--86) wastewater-treatment conditions were tested for trends, and the results indicate substantial changes in water quality of treated effluent and of the White River downstream from Indianapolis after implementation of advanced wastewater treatment. Water quality from 1981 through 1982 was highly variable due to plant construction. Therefore, this time period was excluded from the analysis. Water quality at sample sites located upstream from the wastewater-treatment plants was relatively constant during the period of study (1978-86). Analysis of data from the two plants and downstream from the plants indicates statistically significant decreasing trends in effluent concentrations of total ammonia, 5-day biochemical-oxygen demand, fecal-coliform bacteria, total phosphate, and total solids at all sites where sufficient data were available for testing. Because of in-plant nitrification, increases in nitrate concentration were statistically significant in the two plants and in the White River. The decrease in ammonia concentrations and 5-day biochemical-oxygen demand in the White River resulted in a statistically significant increasing trend in dissolved-oxygen concentration in the river because of reduced oxygen demand for nitrification and biochemical oxidation processes. Following implementation of advanced wastewater treatment, the number of river-quality samples that failed to meet the water-quality standards for ammonia and dissolved oxygen that apply to the White River decreased substantially.

  5. Biosensors with Built-In Biomolecular Logic Gates for Practical Applications

    PubMed Central

    Lai, Yu-Hsuan; Sun, Sin-Cih; Chuang, Min-Chieh

    2014-01-01

    Molecular logic gates, designs constructed with biological and chemical molecules, have emerged as an alternative computing approach to silicon-based logic operations. These molecular computers are capable of receiving and integrating multiple stimuli of biochemical significance to generate a definitive output, opening a new research avenue to advanced diagnostics and therapeutics which demand handling of complex factors and precise control. In molecularly gated devices, Boolean logic computations can be activated by specific inputs and accurately processed via bio-recognition, bio-catalysis, and selective chemical reactions. In this review, we survey recent advances of the molecular logic approaches to practical applications of biosensors, including designs constructed with proteins, enzymes, nucleic acids, nanomaterials, and organic compounds, as well as the research avenues for future development of digitally operating “sense and act” schemes that logically process biochemical signals through networked circuits to implement intelligent control systems. PMID:25587423

  6. Lignin plays a negative role in the biochemical process for producing lignocellulosic biofuels.

    PubMed

    Zeng, Yining; Zhao, Shuai; Yang, Shihui; Ding, Shi-You

    2014-06-01

    A biochemical platform holds the most promising route toward lignocellulosic biofuels, in which polysaccharides are hydrolyzed by cellulase enzymes into simple sugars and fermented to ethanol by microbes. However, these polysaccharides are cross-linked in the plant cell walls with the hydrophobic network of lignin that physically impedes enzymatic deconstruction. A thermochemical pretreatment process is often required to remove or delocalize lignin, which may also generate inhibitors that hamper enzymatic hydrolysis and fermentation. Here we review recent advances in understanding lignin structure in the plant cell walls and the negative roles of lignin in the processes of converting biomass to biofuels. Perspectives and future directions to improve the biomass conversion process are also discussed. Copyright © 2013. Published by Elsevier Ltd.

  7. Biochemical Reconstitution of the WAVE Regulatory Complex

    PubMed Central

    Chen, Baoyu; Padrick, Shae B.; Henry, Lisa; Rosen, Michael K.

    2014-01-01

    The WAVE regulatory complex (WRC) is a 400-KDa heteropentameric protein assembly that plays a central role in controlling actin cytoskeletal dynamics in many cellular processes. The WRC acts by integrating diverse cellular cues and stimulating the actin nucleating activity of the Arp2/3 complex at membranes. Biochemical and biophysical studies of the underlying mechanisms of these processes require large amounts of purified WRC. Recent success in recombinant expression, reconstitution, purification and crystallization of the WRC has greatly advanced our understanding of the inhibition, activation and membrane recruitment mechanisms of this complex. But many important questions remain to be answered. Here we summarize and update the methods developed in our laboratory, which allow reliable and flexible production of tens of milligrams of recombinant WRC of crystallographic quality, sufficient for many biochemical and structural studies. PMID:24630101

  8. Biochemistry of homologous recombination in Escherichia coli.

    PubMed Central

    Kowalczykowski, S C; Dixon, D A; Eggleston, A K; Lauder, S D; Rehrauer, W M

    1994-01-01

    Homologous recombination is a fundamental biological process. Biochemical understanding of this process is most advanced for Escherichia coli. At least 25 gene products are involved in promoting genetic exchange. At present, this includes the RecA, RecBCD (exonuclease V), RecE (exonuclease VIII), RecF, RecG, RecJ, RecN, RecOR, RecQ, RecT, RuvAB, RuvC, SbcCD, and SSB proteins, as well as DNA polymerase I, DNA gyrase, DNA topoisomerase I, DNA ligase, and DNA helicases. The activities displayed by these enzymes include homologous DNA pairing and strand exchange, helicase, branch migration, Holliday junction binding and cleavage, nuclease, ATPase, topoisomerase, DNA binding, ATP binding, polymerase, and ligase, and, collectively, they define biochemical events that are essential for efficient recombination. In addition to these needed proteins, a cis-acting recombination hot spot known as Chi (chi: 5'-GCTGGTGG-3') plays a crucial regulatory function. The biochemical steps that comprise homologous recombination can be formally divided into four parts: (i) processing of DNA molecules into suitable recombination substrates, (ii) homologous pairing of the DNA partners and the exchange of DNA strands, (iii) extension of the nascent DNA heteroduplex; and (iv) resolution of the resulting crossover structure. This review focuses on the biochemical mechanisms underlying these steps, with particular emphases on the activities of the proteins involved and on the integration of these activities into likely biochemical pathways for recombination. Images PMID:7968921

  9. Pharmacological Findings on the Biochemical Bases of Memory Processes: A General View

    PubMed Central

    Izquierdo, Iván; Cammarota, Martín; Medina, Jorge H.; Bevilaqua, Lia R. M.

    2004-01-01

    We have advanced considerably in the past 2 to 3 years in understanding the molecular mechanisms of consolidation, retrieval, and extinction of memories, particularly of fear memory. This advance was mainly due to pharmacological studies in many laboratories using localized brain injections of molecularly specific substances. One area in which significant advances have been made is in understanding that many different brain structures are involved in different memories, and that often several brain regions are involved in processing the same memory. These regions can cooperate or compete with each other, depending on circumstances that are beginning to be identified quite clearly. Another aspect in which major advances were made was retrieval and post-retrieval events, especially extinction, pointing to new therapeutic approaches to fearmotivated mental disorders. PMID:15656267

  10. Economically viable biochemical processes for the advanced rural biorefinery and downstream recovery operations

    USDA-ARS?s Scientific Manuscript database

    Rural biorefineries offer an alternative to traditional ethanol production by providing the opportunity to produce fuel on site to reduce costs associated with biomass transportation thus making the fuel economically viable. Widespread installation of rural biorefineries could lead to increased upt...

  11. Decoding tree DNA

    Treesearch

    M. Thompson Conkle

    1986-01-01

    Check the laboratory reports after your next physical. You'll find information on a number of biochemical processes. Procedures like those used in the medical sciences are yielding valuable information about genetic differences among trees and tree pests. New procedures that provide ways to isolate and move genes are advancing progress in tree improvement. These...

  12. Proteome-wide association studies identify biochemical modules associated with a wing-size phenotype in Drosophila melanogaster.

    PubMed

    Okada, Hirokazu; Ebhardt, H Alexander; Vonesch, Sibylle Chantal; Aebersold, Ruedi; Hafen, Ernst

    2016-09-01

    The manner by which genetic diversity within a population generates individual phenotypes is a fundamental question of biology. To advance the understanding of the genotype-phenotype relationships towards the level of biochemical processes, we perform a proteome-wide association study (PWAS) of a complex quantitative phenotype. We quantify the variation of wing imaginal disc proteomes in Drosophila genetic reference panel (DGRP) lines using SWATH mass spectrometry. In spite of the very large genetic variation (1/36 bp) between the lines, proteome variability is surprisingly small, indicating strong molecular resilience of protein expression patterns. Proteins associated with adult wing size form tight co-variation clusters that are enriched in fundamental biochemical processes. Wing size correlates with some basic metabolic functions, positively with glucose metabolism but negatively with mitochondrial respiration and not with ribosome biogenesis. Our study highlights the power of PWAS to filter functional variants from the large genetic variability in natural populations.

  13. Cofactor engineering for advancing chemical biotechnology.

    PubMed

    Wang, Yipeng; San, Ka-Yiu; Bennett, George N

    2013-12-01

    Cofactors provide redox carriers for biosynthetic reactions, catabolic reactions and act as important agents in transfer of energy for the cell. Recent advances in manipulating cofactors include culture conditions or additive alterations, genetic modification of host pathways for increased availability of desired cofactor, changes in enzyme cofactor specificity, and introduction of novel redox partners to form effective circuits for biochemical processes and biocatalysts. Genetic strategies to employ ferredoxin, NADH and NADPH most effectively in natural or novel pathways have improved yield and efficiency of large-scale processes for fuels and chemicals and have been demonstrated with a variety of microbial organisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Fluorescence lifetime assays: current advances and applications in drug discovery.

    PubMed

    Pritz, Stephan; Doering, Klaus; Woelcke, Julian; Hassiepen, Ulrich

    2011-06-01

    Fluorescence lifetime assays complement the portfolio of established assay formats available in drug discovery, particularly with the recent advances in microplate readers and the commercial availability of novel fluorescent labels. Fluorescence lifetime assists in lowering complexity of compound screening assays, affording a modular, toolbox-like approach to assay development and yielding robust homogeneous assays. To date, materials and procedures have been reported for biochemical assays on proteases, as well as on protein kinases and phosphatases. This article gives an overview of two assay families, distinguished by the origin of the fluorescence signal modulation. The pharmaceutical industry demands techniques with a robust, integrated compound profiling process and short turnaround times. Fluorescence lifetime assays have already helped the drug discovery field, in this sense, by enhancing productivity during the hit-to-lead and lead optimization phases. Future work will focus on covering other biochemical molecular modifications by investigating the detailed photo-physical mechanisms underlying the fluorescence signal.

  15. "Structure and dynamics in complex chemical systems: Gaining new insights through recent advances in time-resolved spectroscopies.” ACS Division of Physical Chemistry Symposium presented at the Fall National ACS Meeting in Boston, MA, August 2015

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

    Crawford, Daniel

    8-Session Symposium on STRUCTURE AND DYNAMICS IN COMPLEX CHEMICAL SYSTEMS: GAINING NEW INSIGHTS THROUGH RECENT ADVANCES IN TIME-RESOLVED SPECTROSCOPIES. The intricacy of most chemical, biochemical, and material processes and their applications are underscored by the complex nature of the environments in which they occur. Substantial challenges for building a global understanding of a heterogeneous system include (1) identifying unique signatures associated with specific structural motifs within the heterogeneous distribution, and (2) resolving the significance of each of multiple time scales involved in both small- and large-scale nuclear reorganization. This symposium focuses on the progress in our understanding of dynamics inmore » complex systems driven by recent innovations in time-resolved spectroscopies and theoretical developments. Such advancement is critical for driving discovery at the molecular level facilitating new applications. Broad areas of interest include: Structural relaxation and the impact of structure on dynamics in liquids, interfaces, biochemical systems, materials, and other heterogeneous environments.« less

  16. Computational modelling of oxygenation processes in enzymes and biomimetic model complexes.

    PubMed

    de Visser, Sam P; Quesne, Matthew G; Martin, Bodo; Comba, Peter; Ryde, Ulf

    2014-01-11

    With computational resources becoming more efficient and more powerful and at the same time cheaper, computational methods have become more and more popular for studies on biochemical and biomimetic systems. Although large efforts from the scientific community have gone into exploring the possibilities of computational methods for studies on large biochemical systems, such studies are not without pitfalls and often cannot be routinely done but require expert execution. In this review we summarize and highlight advances in computational methodology and its application to enzymatic and biomimetic model complexes. In particular, we emphasize on topical and state-of-the-art methodologies that are able to either reproduce experimental findings, e.g., spectroscopic parameters and rate constants, accurately or make predictions of short-lived intermediates and fast reaction processes in nature. Moreover, we give examples of processes where certain computational methods dramatically fail.

  17. Humic Substances: Determining Potential Molecular Regulatory Processes in Plants

    PubMed Central

    Shah, Zahid Hussain; Rehman, Hafiz M.; Akhtar, Tasneem; Alsamadany, Hameed; Hamooh, Bahget T.; Mujtaba, Tahir; Daur, Ihsanullah; Al Zahrani, Yahya; Alzahrani, Hind A. S.; Ali, Shawkat; Yang, Seung H.; Chung, Gyuhwa

    2018-01-01

    Humic substances (HSs) have considerable effects on soil fertility and crop productivity owing to their unique physiochemical and biochemical properties, and play a vital role in establishing biotic and abiotic interactions within the plant rhizosphere. A comprehensive understanding of the mode of action and tissue distribution of HS is, however, required, as this knowledge could be useful for devising advanced rhizospheric management practices. These substances trigger various molecular processes in plant cells, and can strengthen the plant’s tolerance to various kinds of abiotic stresses. HS manifest their effects in cells through genetic, post-transcriptional, and post-translational modifications of signaling entities that trigger different molecular, biochemical, and physiological processes. Understanding of such fundamental mechanisms will provide a better perspective for defining the cues and signaling crosstalk of HS that mediate various metabolic and hormonal networks operating in plant systems. Various regulatory activities and distribution strategies of HS have been discussed in this review. PMID:29593751

  18. Design of a biochemical circuit motif for learning linear functions

    PubMed Central

    Lakin, Matthew R.; Minnich, Amanda; Lane, Terran; Stefanovic, Darko

    2014-01-01

    Learning and adaptive behaviour are fundamental biological processes. A key goal in the field of bioengineering is to develop biochemical circuit architectures with the ability to adapt to dynamic chemical environments. Here, we present a novel design for a biomolecular circuit capable of supervised learning of linear functions, using a model based on chemical reactions catalysed by DNAzymes. To achieve this, we propose a novel mechanism of maintaining and modifying internal state in biochemical systems, thereby advancing the state of the art in biomolecular circuit architecture. We use simulations to demonstrate that the circuit is capable of learning behaviour and assess its asymptotic learning performance, scalability and robustness to noise. Such circuits show great potential for building autonomous in vivo nanomedical devices. While such a biochemical system can tell us a great deal about the fundamentals of learning in living systems and may have broad applications in biomedicine (e.g. autonomous and adaptive drugs), it also offers some intriguing challenges and surprising behaviours from a machine learning perspective. PMID:25401175

  19. Design of a biochemical circuit motif for learning linear functions.

    PubMed

    Lakin, Matthew R; Minnich, Amanda; Lane, Terran; Stefanovic, Darko

    2014-12-06

    Learning and adaptive behaviour are fundamental biological processes. A key goal in the field of bioengineering is to develop biochemical circuit architectures with the ability to adapt to dynamic chemical environments. Here, we present a novel design for a biomolecular circuit capable of supervised learning of linear functions, using a model based on chemical reactions catalysed by DNAzymes. To achieve this, we propose a novel mechanism of maintaining and modifying internal state in biochemical systems, thereby advancing the state of the art in biomolecular circuit architecture. We use simulations to demonstrate that the circuit is capable of learning behaviour and assess its asymptotic learning performance, scalability and robustness to noise. Such circuits show great potential for building autonomous in vivo nanomedical devices. While such a biochemical system can tell us a great deal about the fundamentals of learning in living systems and may have broad applications in biomedicine (e.g. autonomous and adaptive drugs), it also offers some intriguing challenges and surprising behaviours from a machine learning perspective.

  20. Advances in citric acid fermentation by Aspergillus niger: biochemical aspects, membrane transport and modeling.

    PubMed

    Papagianni, Maria

    2007-01-01

    Citric acid is regarded as a metabolite of energy metabolism, of which the concentration will rise to appreciable amounts only under conditions of substantive metabolic imbalances. Citric acid fermentation conditions were established during the 1930s and 1940s, when the effects of various medium components were evaluated. The biochemical mechanism by which Aspergillus niger accumulates citric acid has continued to attract interest even though its commercial production by fermentation has been established for decades. Although extensive basic biochemical research has been carried out with A. niger, the understanding of the events relevant for citric acid accumulation is not completely understood. This review is focused on citric acid fermentation by A. niger. Emphasis is given to aspects of fermentation biochemistry, membrane transport in A. niger and modeling of the production process.

  1. The digital language of amino acids.

    PubMed

    Kurić, L

    2007-11-01

    The subject of this paper is a digital approach to the investigation of the biochemical basis of genetic processes. The digital mechanism of nucleic acid and protein bio-syntheses, the evolution of biomacromolecules and, especially, the biochemical evolution of genetic language have been analyzed by the application of cybernetic methods, information theory and system theory, respectively. This paper reports the discovery of new methods for developing the new technologies in genetics. It is about the most advanced digital technology which is based on program, cybernetics and informational systems and laws. The results in the practical application of the new technology could be useful in bioinformatics, genetics, biochemistry, medicine and other natural sciences.

  2. Characterizing canopy biochemistry from imaging spectroscopy and its application to ecosystem studies

    USGS Publications Warehouse

    Kokaly, R.F.; Asner, Gregory P.; Ollinger, S.V.; Martin, M.E.; Wessman, C.A.

    2009-01-01

    For two decades, remotely sensed data from imaging spectrometers have been used to estimate non-pigment biochemical constituents of vegetation, including water, nitrogen, cellulose, and lignin. This interest has been motivated by the important role that these substances play in physiological processes such as photosynthesis, their relationships with ecosystem processes such as litter decomposition and nutrient cycling, and their use in identifying key plant species and functional groups. This paper reviews three areas of research to improve the application of imaging spectrometers to quantify non-pigment biochemical constituents of plants. First, we examine recent empirical and modeling studies that have advanced our understanding of leaf and canopy reflectance spectra in relation to plant biochemistry. Next, we present recent examples of how spectroscopic remote sensing methods are applied to characterize vegetation canopies, communities and ecosystems. Third, we highlight the latest developments in using imaging spectrometer data to quantify net primary production (NPP) over large geographic areas. Finally, we discuss the major challenges in quantifying non-pigment biochemical constituents of plant canopies from remotely sensed spectra.

  3. Unravelling the mysteries of sub-second biochemical processes using time-resolved mass spectrometry.

    PubMed

    Lento, Cristina; Wilson, Derek J

    2017-05-21

    Many important chemical and biochemical phenomena proceed on sub-second time scales before entering equilibrium. In this mini-review, we explore the history and recent advancements of time-resolved mass spectrometry (TRMS) for the characterization of millisecond time-scale chemical reactions and biochemical processes. TRMS allows for the simultaneous tracking of multiple reactants, intermediates and products with no chromophoric species required, high sensitivity and temporal resolution. The method has most recently been used for the characterization of several short-lived reaction intermediates in rapid chemical reactions. Most of the reactions that occur in living organisms are accelerated by enzymes, with pre-steady state kinetics only attainable using time-resolved methods. TRMS has been increasingly used to monitor the conversion of substrates to products and the resulting changes to the enzyme during catalytic turnover. Early events in protein folding systems have also been elucidated, along with the characterization of dynamics and transient secondary structures in intrinsically disordered proteins. In this review, we will highlight representative examples where TRMS has been applied to study these phenomena.

  4. Environmental biocatalysis: from remediation with enzymes to novel green processes.

    PubMed

    Alcalde, Miguel; Ferrer, Manuel; Plou, Francisco J; Ballesteros, Antonio

    2006-06-01

    Modern biocatalysis is developing new and precise tools to improve a wide range of production processes, which reduce energy and raw material consumption and generate less waste and toxic side-products. Biocatalysis is also achieving new advances in environmental fields, from enzymatic bioremediation to the synthesis of renewable and clean energies and biochemical cleaning of 'dirty' fossil fuels. Despite the obvious benefits of biocatalysis, the major hurdles hindering the exploitation of the repertoire of enzymatic processes are, in many cases, the high production costs and the low yields obtained. This article will discuss these issues, pinpointing specific new advances in recombinant DNA techniques amenable to future biocatalyst development, in addition to drawing the attention of the biotechnology community to the active pursuit and development of environmental biocatalysis, from remediation with enzymes to novel green processes.

  5. Purification and Characterization of Mouse Soluble Receptor for Advanced Glycation End Products (sRAGE)*

    PubMed Central

    Hanford, Lana E.; Enghild, Jan J.; Valnickova, Zuzana; Petersen, Steen V.; Schaefer, Lisa M.; Schaefer, Todd M.; Reinhart, Todd A.; Oury, Tim D.

    2007-01-01

    The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface proteins that has been implicated as a progression factor in a number of pathologic conditions from chronic inflammation to cancer to Alzheimer’s disease. In such conditions, RAGE acts to facilitate pathogenic processes. Its secreted isoform, soluble RAGE or sRAGE, has the ability to prevent RAGE signaling by acting as a decoy. sRAGE has been used successfully in animal models of a range of diseases to antagonize RAGE-mediated pathologic processes. In humans, sRAGE results from alternative splicing of RAGE mRNA. This study was aimed to determine whether the same holds true for mouse sRAGE and, in addition, to biochemically characterize mouse sRAGE. The biochemical characteristics examined include glycosylation and disulfide patterns. In addition, sRAGE was found to bind heparin, which may mediate its distribution in the extracellular matrix and cell surfaces of tissues. Finally, our data indicated that sRAGE in the mouse is likely produced by carboxyl-terminal truncation, in contrast to the alternative splicing mechanism reported in humans. PMID:15381690

  6. Biochemical Conversion Processes of Lignocellulosic Biomass to Fuels and Chemicals - A Review.

    PubMed

    Brethauer, Simone; Studer, Michael H

    2015-01-01

    Lignocellulosic biomass - such as wood, agricultural residues or dedicated energy crops - is a promising renewable feedstock for production of fuels and chemicals that is available at large scale at low cost without direct competition for food usage. Its biochemical conversion in a sugar platform biorefinery includes three main unit operations that are illustrated in this review: the physico-chemical pretreatment of the biomass, the enzymatic hydrolysis of the carbohydrates to a fermentable sugar stream by cellulases and finally the fermentation of the sugars by suitable microorganisms to the target molecules. Special emphasis in this review is put on the technology, commercial status and future prospects of the production of second-generation fuel ethanol, as this process has received most research and development efforts so far. Despite significant advances, high enzyme costs are still a hurdle for large scale competitive lignocellulosic ethanol production. This could be overcome by a strategy termed 'consolidated bioprocessing' (CBP), where enzyme production, enzymatic hydrolysis and fermentation is integrated in one step - either by utilizing one genetically engineered superior microorganism or by creating an artificial co-culture. Insight is provided on both CBP strategies for the production of ethanol as well as of advanced fuels and commodity chemicals.

  7. Advanced Nanoporous Materials for Micro-Gravimetric Sensing to Trace-Level Bio/Chemical Molecules

    PubMed Central

    Xu, Pengcheng; Li, Xinxin; Yu, Haitao; Xu, Tiegang

    2014-01-01

    Functionalized nanoporous materials have been developed recently as bio/chemical sensing materials. Due to the huge specific surface of the nano-materials for molecular adsorption, high hopes have been placed on gravimetric detection with micro/nano resonant cantilevers for ultra-sensitive sensing of low-concentration bio/chemical substances. In order to enhance selectivity of the gravimetric resonant sensors to the target molecules, it is crucial to modify specific groups onto the pore-surface of the nano-materials. By loading the nanoporous sensing material onto the desired region of the mass-type transducers like resonant cantilevers, the micro-gravimetric bio/chemical sensors can be formed. Recently, such micro-gravimetric bio/chemical sensors have been successfully applied for rapid or on-the-spot detection of various bio/chemical molecules at the trace-concentration level. The applicable nanoporous sensing materials include mesoporous silica, zeolite, nanoporous graphene oxide (GO) and so on. This review article focuses on the recent achievements in design, preparation, functionalization and characterization of advanced nanoporous sensing materials for micro-gravimetric bio/chemical sensing. PMID:25313499

  8. Metabolic disorders causing childhood ataxia.

    PubMed

    Parker, Colette C; Evans, Owen B

    2003-09-01

    Ataxia is a common neurologic finding in many disease processes of the nervous system, and has classically been associated with numerous metabolic disorders. An error of metabolism should be considered when the ataxia is either intermittent or progressive. Acute exacerbation or worsening after high protein ingestion, concurrent febrile illness, or other physical stress is also suggestive. A positive family history can be an important diagnostic clue. Progressive molecular and biochemical techniques are revolutionizing this area of medicine, and there has been rapid advancement in understanding of the disease processes.

  9. [Advances in isoprene synthase research].

    PubMed

    Gou, Yan; Liu, Zhongchuan; Wang, Ganggang

    2017-11-25

    Isoprene emission can lead to significant consequence for atmospheric chemistry. In addition, isoprene is a chemical compound for various industrial applications. In the organisms, isoprene is produced by isoprene synthase that eliminates the pyrophosphate from the dimethylallyl diphosphate. As a key enzyme of isoprene formation, isoprene synthase plays an important role in the process of natural emission and artificial synthesis of isoprene. So far, isoprene synthase has been found in various plants. Isoprene synthases from different sources are of conservative structural and similar biochemical properties. In this review, the biochemical and structural characteristics of isoprene synthases from different sources were compared, the catalytic mechanism of isoprene synthase was discussed, and the perspective application of the enzyme in bioengineering was proposed.

  10. Zebrafish: A marvel of high-throughput biology for 21st century toxicology.

    PubMed

    Bugel, Sean M; Tanguay, Robert L; Planchart, Antonio

    2014-09-07

    The evolutionary conservation of genomic, biochemical and developmental features between zebrafish and humans is gradually coming into focus with the end result that the zebrafish embryo model has emerged as a powerful tool for uncovering the effects of environmental exposures on a multitude of biological processes with direct relevance to human health. In this review, we highlight advances in automation, high-throughput (HT) screening, and analysis that leverage the power of the zebrafish embryo model for unparalleled advances in our understanding of how chemicals in our environment affect our health and wellbeing.

  11. Zebrafish: A marvel of high-throughput biology for 21st century toxicology

    PubMed Central

    Bugel, Sean M.; Tanguay, Robert L.; Planchart, Antonio

    2015-01-01

    The evolutionary conservation of genomic, biochemical and developmental features between zebrafish and humans is gradually coming into focus with the end result that the zebrafish embryo model has emerged as a powerful tool for uncovering the effects of environmental exposures on a multitude of biological processes with direct relevance to human health. In this review, we highlight advances in automation, high-throughput (HT) screening, and analysis that leverage the power of the zebrafish embryo model for unparalleled advances in our understanding of how chemicals in our environment affect our health and wellbeing. PMID:25678986

  12. Infrared spectroscopic imaging: Label-free biochemical analysis of stroma and tissue fibrosis.

    PubMed

    Nazeer, Shaiju S; Sreedhar, Hari; Varma, Vishal K; Martinez-Marin, David; Massie, Christine; Walsh, Michael J

    2017-11-01

    Infrared spectroscopic tissue imaging is a potentially powerful adjunct tool to current histopathology techniques. By coupling the biochemical signature obtained through infrared spectroscopy to the spatial information offered by microscopy, this technique can selectively analyze the chemical composition of different features of unlabeled, unstained tissue sections. In the past, the tissue features that have received the most interest were parenchymal and epithelial cells, chiefly due to their involvement in dysplasia and progression to carcinoma; however, the field has recently turned its focus toward stroma and areas of fibrotic change. These components of tissue present an untapped source of biochemical information that can shed light on many diverse disease processes, and potentially hold useful predictive markers for these same pathologies. Here we review the recent applications of infrared spectroscopic imaging to stromal and fibrotic regions of diseased tissue, and explore the potential of this technique to advance current capabilities for tissue analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Which strategy for a protein crystallization project?

    NASA Technical Reports Server (NTRS)

    Kundrot, C. E.

    2004-01-01

    The three-dimensional, atomic-resolution protein structures produced by X-ray crystallography over the past 50+ years have led to tremendous chemical understanding of fundamental biochemical processes. The pace of discovery in protein crystallography has increased greatly with advances in molecular biology, crystallization techniques, cryocrystallography, area detectors, synchrotrons and computing. While the methods used to produce single, well-ordered crystals have also evolved over the years in response to increased understanding and advancing technology, crystallization strategies continue to be rooted in trial-and-error approaches. This review summarizes the current approaches in protein crystallization and surveys the first results to emerge from the structural genomics efforts.

  14. Which Strategy for a Protein Crystallization Project?

    NASA Technical Reports Server (NTRS)

    Kundrot, Craig E.

    2003-01-01

    The three-dimensional, atomic-resolution protein structures produced by X-ray crystallography over the past 50+ years have led to tremendous chemical understanding of fundamental biochemical processes. The pace of discovery in protein crystallography has increased greatly with advances in molecular biology, crystallization techniques, cryo-crystallography, area detectors, synchrotrons and computing. While the methods used to produce single, well-ordered crystals have also evolved over the years in response to increased understanding and advancing technology, crystallization strategies continue to be rooted in trial-and-error approaches. This review summarizes the current approaches in protein crystallization and surveys the first results to emerge from the structural genomics efforts.

  15. The future of imaging spectroscopy - Prospective technologies and applications

    USGS Publications Warehouse

    Schaepman, M.E.; Green, R.O.; Ungar, S.G.; Curtiss, B.; Boardman, J.; Plaza, A.J.; Gao, B.-C.; Ustin, S.; Kokaly, R.; Miller, J.R.; Jacquemoud, S.; Ben-Dor, E.; Clark, R.; Davis, C.; Dozier, J.; Goodenough, D.G.; Roberts, D.; Swayze, G.; Milton, E.J.; Goetz, A.F.H.

    2006-01-01

    Spectroscopy has existed for more than three centuries now. Nonetheless, significant scientific advances have been achieved. We discuss the history of spectroscopy in relation to emerging technologies and applications. Advanced focal plane arrays, optical design, and intelligent on-board logic are prime prospective technologies. Scalable approaches in pre-processing of imaging spectrometer data will receive additional focus. Finally, we focus on new applications monitoring transitional ecological zones, where human impact and disturbance have highest impact as well as in monitoring changes in our natural resources and environment We conclude that imaging spectroscopy enables mapping of biophysical and biochemical variables of the Earth's surface and atmospheric composition with unprecedented accuracy.

  16. Refining each process step to accelerate the development of biorefineries

    DOE PAGES

    Chandra, Richard P.; Ragauskas, Art J.

    2016-06-21

    Research over the past decade has been mainly focused on overcoming hurdles in the pretreatment, enzymatic hydrolysis, and fermentation steps of biochemical processing. Pretreatments have improved significantly in their ability to fractionate and recover the cellulose, hemicellulose, and lignin components of biomass while producing substrates containing carbohydrates that can be easily broken down by hydrolytic enzymes. There is a rapid movement towards pretreatment processes that incorporate mechanical treatments that make use of existing infrastructure in the pulp and paper industry, which has experienced a downturn in its traditional markets. Enzyme performance has also made great strides with breakthrough developments inmore » nonhydrolytic protein components, such as lytic polysaccharide monooxygenases, as well as the improvement of enzyme cocktails.The fermentability of pretreated and hydrolyzed sugar streams has been improved through strategies such as the use of reducing agents for detoxification, strain selection, and strain improvements. Although significant progress has been made, tremendous challenges still remain to advance each step of biochemical conversion, especially when processing woody biomass. In addition to technical and scale-up issues within each step of the bioconversion process, biomass feedstock supply and logistics challenges still remain at the forefront of biorefinery research.« less

  17. Advances in methods for detection of anaerobic ammonium oxidizing (anammox) bacteria.

    PubMed

    Li, Meng; Gu, Ji-Dong

    2011-05-01

    Anaerobic ammonium oxidation (anammox), the biochemical process oxidizing ammonium into dinitrogen gas using nitrite as an electron acceptor, has only been recognized for its significant role in the global nitrogen cycle not long ago, and its ubiquitous distribution in a wide range of environments has changed our knowledge about the contributors to the global nitrogen cycle. Currently, several groups of methods are used in detection of anammox bacteria based on their physiological and biochemical characteristics, cellular chemical composition, and both 16S rRNA gene and selective functional genes as biomarkers, including hydrazine oxidoreductase and nitrite reductase encoding genes hzo and nirS, respectively. Results from these methods coupling with advances in quantitative PCR, reverse transcription of mRNA genes and stable isotope labeling have improved our understanding on the distribution, diversity, and activity of anammox bacteria in different environments both natural and engineered ones. In this review, we summarize these methods used in detection of anammox bacteria from various environments, highlight the strengths and weakness of these methods, and also discuss the new development potentials on the existing and new techniques in the future.

  18. Mathematical models of cell motility.

    PubMed

    Flaherty, Brendan; McGarry, J P; McHugh, P E

    2007-01-01

    Cell motility is an essential biological action in the creation, operation and maintenance of our bodies. Developing mathematical models elucidating cell motility will greatly advance our understanding of this fundamental biological process. With accurate models it is possible to explore many permutations of the same event and concisely investigate their outcome. While great advancements have been made in experimental studies of cell motility, it now has somewhat fallen on mathematical models to taking a leading role in future developments. The obvious reason for this is the complexity of cell motility. Employing the processing power of today's computers will give researches the ability to run complex biophysical and biochemical scenarios, without the inherent difficulty and time associated with in vitro investigations. Before any great advancement can be made, the basics of cell motility will have to be well-defined. Without this, complicated mathematical models will be hindered by their inherent conjecture. This review will look at current mathematical investigations of cell motility, explore the reasoning behind such work and conclude with how best to advance this interesting and challenging research area.

  19. Biomolecular logic systems: applications to biosensors and bioactuators

    NASA Astrophysics Data System (ADS)

    Katz, Evgeny

    2014-05-01

    The paper presents an overview of recent advances in biosensors and bioactuators based on the biocomputing concept. Novel biosensors digitally process multiple biochemical signals through Boolean logic networks of coupled biomolecular reactions and produce output in the form of YES/NO response. Compared to traditional single-analyte sensing devices, biocomputing approach enables a high-fidelity multi-analyte biosensing, particularly beneficial for biomedical applications. Multi-signal digital biosensors thus promise advances in rapid diagnosis and treatment of diseases by processing complex patterns of physiological biomarkers. Specifically, they can provide timely detection and alert to medical emergencies, along with an immediate therapeutic intervention. Application of the biocomputing concept has been successfully demonstrated for systems performing logic analysis of biomarkers corresponding to different injuries, particularly exemplified for liver injury. Wide-ranging applications of multi-analyte digital biosensors in medicine, environmental monitoring and homeland security are anticipated. "Smart" bioactuators, for example for signal-triggered drug release, were designed by interfacing switchable electrodes and biocomputing systems. Integration of novel biosensing and bioactuating systems with the biomolecular information processing systems keeps promise for further scientific advances and numerous practical applications.

  20. Role of biomolecular logic systems in biosensors and bioactuators

    NASA Astrophysics Data System (ADS)

    Mailloux, Shay; Katz, Evgeny

    2014-09-01

    An overview of recent advances in biosensors and bioactuators based on biocomputing systems is presented. Biosensors digitally process multiple biochemical signals through Boolean logic networks of coupled biomolecular reactions and produce an output in the form of a YES/NO response. Compared to traditional single-analyte sensing devices, the biocomputing approach enables high-fidelity multianalyte biosensing, which is particularly beneficial for biomedical applications. Multisignal digital biosensors thus promise advances in rapid diagnosis and treatment of diseases by processing complex patterns of physiological biomarkers. Specifically, they can provide timely detection and alert medical personnel of medical emergencies together with immediate therapeutic intervention. Application of the biocomputing concept has been successfully demonstrated for systems performing logic analysis of biomarkers corresponding to different injuries, particularly as exemplified for liver injury. Wide-ranging applications of multianalyte digital biosensors in medicine, environmental monitoring, and homeland security are anticipated. "Smart" bioactuators, for signal-triggered drug release, for example, were designed by interfacing switchable electrodes with biocomputing systems. Integration of biosensing and bioactuating systems with biomolecular information processing systems advances the potential for further scientific innovations and various practical applications.

  1. Hyperspectral remote sensing of vegetation: knowledge gain and knowledge gap after 50 years of research (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Thenkabail, Prasad S.

    2017-04-01

    This presentation summarizes the advances made over 40+ years in understanding, modeling, and mapping terrestrial vegetation as reported in the new book on "Hyperspectral Remote Sensing of Vegetation" (Publisher:Taylor and Francis inc.). The advent of spaceborne hyperspectral sensors or imaging spectroscopy (e.g., NASA's Hyperion, ESA's PROBA, and upcoming Italy's ASI's Prisma, Germany's DLR's EnMAP, Japanese HIUSI, NASA's HyspIRI) as well as the advances made in processing when handling large volumes of hyperspectral data have generated tremendous interest in advancing the hyperspectral applications' knowledge base to large areas. Advances made in using hyperspectral data, relative to broadband data, include: (a) significantly improved characterization and modeling of a wide array of biophysical and biochemical properties of vegetation, (b) ability to discriminate plant species and vegetation types with high degree of accuracy, (c) reducing uncertainties in determining net primary productivity or carbon assessments from terrestrial vegetation, (d) improved crop productivity and water productivity models, (e) ability to assess stress resulting from causes such as management practices, pests and disease, water deficit or water excess, and (f) establishing more sensitive wavebands and indices to study vegetation characteristics. The presentation will discuss topics such as: (1) hyperspectral sensors and their characteristics, (2) methods of overcoming the Hughes phenomenon, (3) characterizing biophysical and biochemical properties, (4) advances made in using hyperspectral data in modeling evapotranspiration or actual water use by plants, (5) study of phenology, light use efficiency, and gross primary productivity, (5) improved accuracies in species identification and land cover classifications, and (6) applications in precision farming.

  2. Advanced microscopic methods for the detection of adhesion barriers in immunology in medical imaging

    NASA Astrophysics Data System (ADS)

    Lawrence, Shane

    2017-07-01

    Advanced methods of microscopy and advanced techniques of analysis stemming therefrom have developed greatly in the past few years.The use of single discrete methods has given way to the combination of methods which means an increase in data for processing to progress to the analysis and diagnosis of ailments and diseases which can be viewed by each and any method.This presentation shows the combination of such methods and gives example of the data which arises from each individual method and the combined methodology and suggests how such data can be streamlined to enable conclusions to be drawn about the particular biological and biochemical considerations that arise.In this particular project the subject of the methodology was human lactoferrin and the relation of the adhesion properties of hlf in the overcoming of barriers to adhesion mainly on the perimeter of the cellular unit and how this affects the process of immunity in any particular case.

  3. Single-molecule live-cell imaging of bacterial DNA repair and damage tolerance.

    PubMed

    Ghodke, Harshad; Ho, Han; van Oijen, Antoine M

    2018-02-19

    Genomic DNA is constantly under threat from intracellular and environmental factors that damage its chemical structure. Uncorrected DNA damage may impede cellular propagation or even result in cell death, making it critical to restore genomic integrity. Decades of research have revealed a wide range of mechanisms through which repair factors recognize damage and co-ordinate repair processes. In recent years, single-molecule live-cell imaging methods have further enriched our understanding of how repair factors operate in the crowded intracellular environment. The ability to follow individual biochemical events, as they occur in live cells, makes single-molecule techniques tremendously powerful to uncover the spatial organization and temporal regulation of repair factors during DNA-repair reactions. In this review, we will cover practical aspects of single-molecule live-cell imaging and highlight recent advances accomplished by the application of these experimental approaches to the study of DNA-repair processes in prokaryotes. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  4. Designing degradable hydrogels for orthogonal control of cell microenvironments

    PubMed Central

    Kharkar, Prathamesh M.

    2013-01-01

    Degradable and cell-compatible hydrogels can be designed to mimic the physical and biochemical characteristics of native extracellular matrices and provide tunability of degradation rates and related properties under physiological conditions. Hence, such hydrogels are finding widespread application in many bioengineering fields, including controlled bioactive molecule delivery, cell encapsulation for controlled three-dimensional culture, and tissue engineering. Cellular processes, such as adhesion, proliferation, spreading, migration, and differentiation, can be controlled within degradable, cell-compatible hydrogels with temporal tuning of biochemical or biophysical cues, such as growth factor presentation or hydrogel stiffness. However, thoughtful selection of hydrogel base materials, formation chemistries, and degradable moieties is necessary to achieve the appropriate level of property control and desired cellular response. In this review, hydrogel design considerations and materials for hydrogel preparation, ranging from natural polymers to synthetic polymers, are overviewed. Recent advances in chemical and physical methods to crosslink hydrogels are highlighted, as well as recent developments in controlling hydrogel degradation rates and modes of degradation. Special attention is given to spatial or temporal presentation of various biochemical and biophysical cues to modulate cell response in static (i.e., non-degradable) or dynamic (i.e., degradable) microenvironments. This review provides insight into the design of new cell-compatible, degradable hydrogels to understand and modulate cellular processes for various biomedical applications. PMID:23609001

  5. X-ray crystallography over the past decade for novel drug discovery - where are we heading next?

    PubMed

    Zheng, Heping; Handing, Katarzyna B; Zimmerman, Matthew D; Shabalin, Ivan G; Almo, Steven C; Minor, Wladek

    2015-01-01

    Macromolecular X-ray crystallography has been the primary methodology for determining the three-dimensional structures of proteins, nucleic acids and viruses. Structural information has paved the way for structure-guided drug discovery and laid the foundations for structural bioinformatics. However, X-ray crystallography still has a few fundamental limitations, some of which may be overcome and complemented using emerging methods and technologies in other areas of structural biology. This review describes how structural knowledge gained from X-ray crystallography has been used to advance other biophysical methods for structure determination (and vice versa). This article also covers current practices for integrating data generated by other biochemical and biophysical methods with those obtained from X-ray crystallography. Finally, the authors articulate their vision about how a combination of structural and biochemical/biophysical methods may improve our understanding of biological processes and interactions. X-ray crystallography has been, and will continue to serve as, the central source of experimental structural biology data used in the discovery of new drugs. However, other structural biology techniques are useful not only to overcome the major limitation of X-ray crystallography, but also to provide complementary structural data that is useful in drug discovery. The use of recent advancements in biochemical, spectroscopy and bioinformatics methods may revolutionize drug discovery, albeit only when these data are combined and analyzed with effective data management systems. Accurate and complete data management is crucial for developing experimental procedures that are robust and reproducible.

  6. Femtosecond Laser Fabrication of Monolithically Integrated Microfluidic Sensors in Glass

    PubMed Central

    He, Fei; Liao, Yang; Lin, Jintian; Song, Jiangxin; Qiao, Lingling; Cheng, Ya; Sugioka, Koji

    2014-01-01

    Femtosecond lasers have revolutionized the processing of materials, since their ultrashort pulse width and extremely high peak intensity allows high-quality micro- and nanofabrication of three-dimensional (3D) structures. This unique capability opens up a new route for fabrication of microfluidic sensors for biochemical applications. The present paper presents a comprehensive review of recent advancements in femtosecond laser processing of glass for a variety of microfluidic sensor applications. These include 3D integration of micro-/nanofluidic, optofluidic, electrofluidic, surface-enhanced Raman-scattering devices, in addition to fabrication of devices for microfluidic bioassays and lab-on-fiber sensors. This paper describes the unique characteristics of femtosecond laser processing and the basic concepts involved in femtosecond laser direct writing. Advanced spatiotemporal beam shaping methods are also discussed. Typical examples of microfluidic sensors fabricated using femtosecond lasers are then highlighted, and their applications in chemical and biological sensing are described. Finally, a summary of the technology is given and the outlook for further developments in this field is considered. PMID:25330047

  7. Review of cellular mechanotransduction

    NASA Astrophysics Data System (ADS)

    Wang, Ning

    2017-06-01

    Living cells and tissues experience physical forces and chemical stimuli in the human body. The process of converting mechanical forces into biochemical activities and gene expression is mechanochemical transduction or mechanotransduction. Significant advances have been made in understanding mechanotransduction at the cellular and molecular levels over the last two decades. However, major challenges remain in elucidating how a living cell integrates signals from mechanotransduction with chemical signals to regulate gene expression and to generate coherent biological responses in living tissues in physiological conditions and diseases.

  8. Advanced Biotelemetry Systems for Space Life Sciences: PH Telemetry

    NASA Technical Reports Server (NTRS)

    Hines, John W.; Somps, Chris; Ricks, Robert; Kim, Lynn; Connolly, John P. (Technical Monitor)

    1995-01-01

    The SENSORS 2000! (S2K!) program at NASA's Ames Research Center is currently developing a biotelemetry system for monitoring pH and temperature in unrestrained subjects. This activity is part of a broader scope effort to provide an Advanced Biotelemetry System (ABTS) for use in future space life sciences research. Many anticipated research endeavors will require biomedical and biochemical sensors and related instrumentation to make continuous inflight measurements in a variable-gravity environment. Since crew time is limited, automated data acquisition, data processing, data storage, and subject health monitoring are required. An automated biochemical and physiological data acquisition system based on non invasive or implantable biotelemetry technology will meet these requirements. The ABTS will ultimately acquire a variety of physiological measurands including temperature, biopotentials (e.g. ECG, EEG, EMG, EOG), blood pressure, flow and dimensions, as well as chemical and biological parameters including pH. Development activities are planned in evolutionary, leveraged steps. Near-term activities include 1) development of a dual channel pH/temperature telemetry system, and 2) development of a low bandwidth, 4-channel telemetry system, that measures temperature, heart rate, pressure, and pH. This abstract describes the pH/temperature telemeter.

  9. Connecting Biochemical Photosynthesis Models with Crop Models to Support Crop Improvement

    PubMed Central

    Wu, Alex; Song, Youhong; van Oosterom, Erik J.; Hammer, Graeme L.

    2016-01-01

    The next advance in field crop productivity will likely need to come from improving crop use efficiency of resources (e.g., light, water, and nitrogen), aspects of which are closely linked with overall crop photosynthetic efficiency. Progress in genetic manipulation of photosynthesis is confounded by uncertainties of consequences at crop level because of difficulties connecting across scales. Crop growth and development simulation models that integrate across biological levels of organization and use a gene-to-phenotype modeling approach may present a way forward. There has been a long history of development of crop models capable of simulating dynamics of crop physiological attributes. Many crop models incorporate canopy photosynthesis (source) as a key driver for crop growth, while others derive crop growth from the balance between source- and sink-limitations. Modeling leaf photosynthesis has progressed from empirical modeling via light response curves to a more mechanistic basis, having clearer links to the underlying biochemical processes of photosynthesis. Cross-scale modeling that connects models at the biochemical and crop levels and utilizes developments in upscaling leaf-level models to canopy models has the potential to bridge the gap between photosynthetic manipulation at the biochemical level and its consequences on crop productivity. Here we review approaches to this emerging cross-scale modeling framework and reinforce the need for connections across levels of modeling. Further, we propose strategies for connecting biochemical models of photosynthesis into the cross-scale modeling framework to support crop improvement through photosynthetic manipulation. PMID:27790232

  10. Connecting Biochemical Photosynthesis Models with Crop Models to Support Crop Improvement.

    PubMed

    Wu, Alex; Song, Youhong; van Oosterom, Erik J; Hammer, Graeme L

    2016-01-01

    The next advance in field crop productivity will likely need to come from improving crop use efficiency of resources (e.g., light, water, and nitrogen), aspects of which are closely linked with overall crop photosynthetic efficiency. Progress in genetic manipulation of photosynthesis is confounded by uncertainties of consequences at crop level because of difficulties connecting across scales. Crop growth and development simulation models that integrate across biological levels of organization and use a gene-to-phenotype modeling approach may present a way forward. There has been a long history of development of crop models capable of simulating dynamics of crop physiological attributes. Many crop models incorporate canopy photosynthesis (source) as a key driver for crop growth, while others derive crop growth from the balance between source- and sink-limitations. Modeling leaf photosynthesis has progressed from empirical modeling via light response curves to a more mechanistic basis, having clearer links to the underlying biochemical processes of photosynthesis. Cross-scale modeling that connects models at the biochemical and crop levels and utilizes developments in upscaling leaf-level models to canopy models has the potential to bridge the gap between photosynthetic manipulation at the biochemical level and its consequences on crop productivity. Here we review approaches to this emerging cross-scale modeling framework and reinforce the need for connections across levels of modeling. Further, we propose strategies for connecting biochemical models of photosynthesis into the cross-scale modeling framework to support crop improvement through photosynthetic manipulation.

  11. The impact of biotechnological advances on the future of US bioenergy

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

    Davison, Brian H.; Brandt, Craig C.; Guss, Adam M.

    Modern biotechnology has the potential to substantially advance the feasibility, structure, and efficiency of future biofuel supply chains. Advances might be direct or indirect. A direct advance would be improving the efficiency of biochemical conversion processes and feedstock production. Direct advances in processing may involve developing improved enzymes and bacteria to convert lignocellulosic feedstocks to ethanol. Progress in feedstock production could include enhancing crop yields via genetic modification or the selection of specific natural variants and breeds. Other direct results of biotechnology might increase the production of fungible biofuels and bioproducts, which would impact the supply chain. Indirect advances mightmore » include modifications to dedicated bioenergy crops that enable them to grow on marginal lands rather than land needed for food production. This study assesses the feasibility and advantages of near-future (10-year) biotechnological developments for a US biomass-based supply chain for bioenergy production. We assume a simplified supply chain of feedstock, logistics and land use, conversion, and products and utilization. The primary focus is how likely developments in feedstock production and conversion technologies will impact bioenergy and biofuels in the USA; a secondary focus is other innovative uses of biotechnologies in the energy arenas. The assessment addresses near-term biofuels based on starch, sugar, and cellulosic feedstocks and considers some longer-term options, such as oil-crop and algal technologies.« less

  12. The impact of biotechnological advances on the future of US bioenergy

    DOE PAGES

    Davison, Brian H.; Brandt, Craig C.; Guss, Adam M.; ...

    2015-05-14

    Modern biotechnology has the potential to substantially advance the feasibility, structure, and efficiency of future biofuel supply chains. Advances might be direct or indirect. A direct advance would be improving the efficiency of biochemical conversion processes and feedstock production. Direct advances in processing may involve developing improved enzymes and bacteria to convert lignocellulosic feedstocks to ethanol. Progress in feedstock production could include enhancing crop yields via genetic modification or the selection of specific natural variants and breeds. Other direct results of biotechnology might increase the production of fungible biofuels and bioproducts, which would impact the supply chain. Indirect advances mightmore » include modifications to dedicated bioenergy crops that enable them to grow on marginal lands rather than land needed for food production. This study assesses the feasibility and advantages of near-future (10-year) biotechnological developments for a US biomass-based supply chain for bioenergy production. We assume a simplified supply chain of feedstock, logistics and land use, conversion, and products and utilization. The primary focus is how likely developments in feedstock production and conversion technologies will impact bioenergy and biofuels in the USA; a secondary focus is other innovative uses of biotechnologies in the energy arenas. The assessment addresses near-term biofuels based on starch, sugar, and cellulosic feedstocks and considers some longer-term options, such as oil-crop and algal technologies.« less

  13. Age and stress as determinants of the severity of hyperthyroidism caused by Graves' disease in newly diagnosed patients.

    PubMed

    Vos, Xander G; Smit, Natalie; Endert, Erik; Brosschot, Jos F; Tijssen, Jan G P; Wiersinga, Wilmar M

    2009-02-01

    The evidence that stress may provoke Graves' hyperthyroidism in genetically susceptible subjects is substantial. Whether exposure to stress is related to the severity of thyrotoxicosis has not been studied. Advancing age is associated with not only less severe Graves' hyperthyroidism but also self-reported stress. We tested the hypothesis whether advancing age is associated with less exposure to stress, resulting in a lower immunological response, and less severe Graves' hyperthyroidism. Cross-sectional multicenter study. Two hundred and sixty-three consecutive untreated patients with a first episode of Graves' hyperthyroidism were included. The severity of Graves' hyperthyroidism was evaluated biochemically (freeT(4)-index and freeT(3)-index, thyrotropin-binding inhibitory immunoglobulin (TBII)) and clinically by the hyperthyroid symptom scale score (HSS score). Stress exposure was quantitated by three questionnaires. Advancing age was associated with less severe Graves' hyperthyroidism, both biochemically by lower serum freeT(3)-index and freeT(4)-index (P<0.01), lower serum TBII (P=0.05), and clinically by lower HSS scores (P=0.04) and smaller goiter size (P<0.01). FreeT(3)-index and freeT(4)-index were directly associated with HSS scores (P<0.01). Stress scores were associated with HSS scores (P<0.01) but not with biochemical severity of Graves' hyperthyroidism. Advancing age was associated with lower scores for stress exposure. Multivariate regression analysis showed that HSS score was independently related to the tendency to report negative feelings (P<0.01) but not to other stress scores and also not to age. Advancing age is associated with less exposure to stress, lower serum TBII and less severe clinical and biochemical Graves' hyperthyroidism. Because no direct relationship exists between stress exposure and TBII or freeT(3)-index and freeT(4)-index, we reject our hypothesis that less stress is causally related to biochemically less severe Graves' hyperthyroidism in old age. HSS score is primarily determined by negative feelings and not by age.

  14. Engineering microbial fatty acid metabolism for biofuels and biochemicals.

    PubMed

    Marella, Eko Roy; Holkenbrink, Carina; Siewers, Verena; Borodina, Irina

    2018-04-01

    Traditional oleochemical industry chemically processes animal fats and plant oils to produce detergents, lubricants, biodiesel, plastics, coatings, and other products. Biotechnology offers an alternative process, where the same oleochemicals can be produced from abundant biomass feedstocks using microbial catalysis. This review summarizes the recent advances in the engineering of microbial metabolism for production of fatty acid-derived products. We highlight the efforts in engineering the central carbon metabolism, redox metabolism, controlling the chain length of the products, and obtaining metabolites with different functionalities. The prospects of commercializing microbial oleochemicals are also discussed. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Recent advances in the neurophysiology of chronic pain.

    PubMed

    Baker, Kylie

    2005-02-01

    The chronic pain syndrome patient has become the 'leper' of emergency medicine. There are no emergency medicine guidelines and minimal research into managing this challenging group of patients. To summarize the recent advances in laboratory research into the development of chronic pain that have relevance to emergency management. When the level of supporting evidence is low, it is imperative that emergency physicians understand the physiology that underpins those expert opinions upon which they base their treatment strategies. Literature was searched via Medline, Cochrane, Cinahl, and PsycINFO from 1996 to 2004, under 'chronic pain and emergency management'. Medline from 1996 was searched for 'chronic pain and prevention', 'chronic pain and emergency' and 'chronic pain'. Bibliographies were manually searched for older keynote articles. Advances in understanding the biochemical changes of chronic pain are paralleled by lesser known advances in delineation of the corticol processing. Drug manipulation causes complex action and reaction in chronic pain. Emergency physicians must also optimize cognitive and behavioural aspects of treatment to successfully manage this systemic disease.

  16. Quantum Mechanics/Molecular Mechanics Modeling of Enzymatic Processes: Caveats and Breakthroughs.

    PubMed

    Quesne, Matthew G; Borowski, Tomasz; de Visser, Sam P

    2016-02-18

    Nature has developed large groups of enzymatic catalysts with the aim to transfer substrates into useful products, which enables biosystems to perform all their natural functions. As such, all biochemical processes in our body (we drink, we eat, we breath, we sleep, etc.) are governed by enzymes. One of the problems associated with research on biocatalysts is that they react so fast that details of their reaction mechanisms cannot be obtained with experimental work. In recent years, major advances in computational hardware and software have been made and now large (bio)chemical systems can be studied using accurate computational techniques. One such technique is the quantum mechanics/molecular mechanics (QM/MM) technique, which has gained major momentum in recent years. Unfortunately, it is not a black-box method that is easily applied, but requires careful set-up procedures. In this work we give an overview on the technical difficulties and caveats of QM/MM and discuss work-protocols developed in our groups for running successful QM/MM calculations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Chemical and Biochemical Approaches in the Study of Histone Methylation and Demethylation

    PubMed Central

    Li, Keqin Kathy; Luo, Cheng; Wang, Dongxia; Jiang, Hualiang; Zheng, Y. George

    2014-01-01

    Histone methylation represents one of the most critical epigenetic events in DNA function regulation in eukaryotic organisms. Classic molecular biology and genetics tools provide significant knowledge about mechanisms and physiological roles of histone methyltransferases and demethylases in various cellular processes. In addition to this stream line, development and application of chemistry and chemistry-related techniques are increasingly involved in biological study, and provide information otherwise difficulty to obtain by standard molecular biology methods. Herein, we review recent achievements and progress in developing and applying chemical and biochemical approaches in the study of histone methylation, including chromatin immunoprecipitation (ChIP), chemical ligation, mass spectrometry (MS), biochemical assays, and inhibitor development. These technological advances allow histone methylation to be studied from genome-wide level to molecular and atomic levels. With ChIP technology, information can be obtained about precise mapping of histone methylation patterns at specific promoters, genes or other genomic regions. MS is particularly useful in detecting and analyzing methylation marks in histone and nonhistone protein substrates. Chemical approaches that permit site-specific incorporation of methyl groups into histone proteins greatly facilitate the investigation of the biological impacts of methylation at individual modification sites. Discovery and design of selective organic inhibitors of histone methyltransferases and demethylases provide chemical probes to interrogate methylation-mediated cellular pathways. Overall, these chemistry-related technological advances have greatly improved our understanding of the biological functions of histone methylation in normal physiology and diseased states, and also are of great potential to translate basic epigenetics research into diagnostic and therapeutic application in the clinic. PMID:22777714

  18. X-ray crystallography over the past decade for novel drug discovery – where are we heading next?

    PubMed Central

    Zheng, Heping; Handing, Katarzyna B; Zimmerman, Matthew D; Shabalin, Ivan G; Almo, Steven C; Minor, Wladek

    2015-01-01

    Introduction Macromolecular X-ray crystallography has been the primary methodology for determining the three-dimensional structures of proteins, nucleic acids and viruses. Structural information has paved the way for structure-guided drug discovery and laid the foundations for structural bioinformatics. However, X-ray crystallography still has a few fundamental limitations, some of which may be overcome and complemented using emerging methods and technologies in other areas of structural biology. Areas covered This review describes how structural knowledge gained from X-ray crystallography has been used to advance other biophysical methods for structure determination (and vice versa). This article also covers current practices for integrating data generated by other biochemical and biophysical methods with those obtained from X-ray crystallography. Finally, the authors articulate their vision about how a combination of structural and biochemical/biophysical methods may improve our understanding of biological processes and interactions. Expert opinion X-ray crystallography has been, and will continue to serve as, the central source of experimental structural biology data used in the discovery of new drugs. However, other structural biology techniques are useful not only to overcome the major limitation of X-ray crystallography, but also to provide complementary structural data that is useful in drug discovery. The use of recent advancements in biochemical, spectroscopy and bioinformatics methods may revolutionize drug discovery, albeit only when these data are combined and analyzed with effective data management systems. Accurate and complete data management is crucial for developing experimental procedures that are robust and reproducible. PMID:26177814

  19. Combinatorial genetic perturbation to refine metabolic circuits for producing biofuels and biochemicals.

    PubMed

    Kim, Hyo Jin; Turner, Timothy Lee; Jin, Yong-Su

    2013-11-01

    Recent advances in metabolic engineering have enabled microbial factories to compete with conventional processes for producing fuels and chemicals. Both rational and combinatorial approaches coupled with synthetic and systematic tools play central roles in metabolic engineering to create and improve a selected microbial phenotype. Compared to knowledge-based rational approaches, combinatorial approaches exploiting biological diversity and high-throughput screening have been demonstrated as more effective tools for improving various phenotypes of interest. In particular, identification of unprecedented targets to rewire metabolic circuits for maximizing yield and productivity of a target chemical has been made possible. This review highlights general principles and the features of the combinatorial approaches using various libraries to implement desired phenotypes for strain improvement. In addition, recent applications that harnessed the combinatorial approaches to produce biofuels and biochemicals will be discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. A review of models of fluctuating protrusion and retraction patterns at the leading edge of motile cells.

    PubMed

    Ryan, Gillian L; Watanabe, Naoki; Vavylonis, Dimitrios

    2012-04-01

    A characteristic feature of motile cells as they undergo a change in motile behavior is the development of fluctuating exploratory motions of the leading edge, driven by actin polymerization. We review quantitative models of these protrusion and retraction phenomena. Theoretical studies have been motivated by advances in experimental and computational methods that allow controlled perturbations, single molecule imaging, and analysis of spatiotemporal correlations in microscopic images. To explain oscillations and waves of the leading edge, most theoretical models propose nonlinear interactions and feedback mechanisms among different components of the actin cytoskeleton system. These mechanisms include curvature-sensing membrane proteins, myosin contraction, and autocatalytic biochemical reaction kinetics. We discuss how the combination of experimental studies with modeling promises to quantify the relative importance of these biochemical and biophysical processes at the leading edge and to evaluate their generality across cell types and extracellular environments. Copyright © 2012 Wiley Periodicals, Inc.

  1. Novel Advances in Shotgun Lipidomics for Biology and Medicine

    PubMed Central

    Wang, Miao; Wang, Chunyan; Han, Rowland H.; Han, Xianlin

    2015-01-01

    The field of lipidomics, as coined in 2003, has made profound advances and been rapidly expanded. The mass spectrometry-based strategies of this analytical methodology-oriented research discipline for lipid analysis are largely fallen into three categories: direct infusion-based shotgun lipidomics, liquid chromatography-mass spectrometry-based platforms, and matrix-assisted laser desorption/ionization mass spectrometry-based approaches (particularly in imagining lipid distribution in tissues or cells). This review focuses on shotgun lipidomics. After briefly introducing its fundamentals, the major materials of this article cover its recent advances. These include the novel methods of lipid extraction, novel shotgun lipidomics strategies for identification and quantification of previously hardly accessible lipid classes and molecular species including isomers, and novel tools for processing and interpretation of lipidomics data. Representative applications of advanced shotgun lipidomics for biological and biomedical research are also presented in this review. We believe that with these novel advances in shotgun lipidomics, this approach for lipid analysis should become more comprehensive and high throughput, thereby greatly accelerating the lipidomics field to substantiate the aberrant lipid metabolism, signaling, trafficking, and homeostasis under pathological conditions and their underpinning biochemical mechanisms. PMID:26703190

  2. Gel-free/label-free proteomic, photosynthetic, and biochemical analysis of cowpea (Vigna unguiculata [L.] Walp.) resistance against Cowpea severe mosaic virus (CPSMV).

    PubMed

    Varela, Anna Lidia N; Komatsu, Setsuko; Wang, Xin; Silva, Rodolpho G G; Souza, Pedro Filho N; Lobo, Ana Karla M; Vasconcelos, Ilka M; Silveira, Joaquim A G; Oliveira, Jose T A

    2017-06-23

    Cowpea severe mosaic virus (CPSMV) causes significant losses in cowpea (Vigna unguiculata) production. In this present study biochemical, physiological, and proteomic analysis were done to identify pathways and defense proteins that are altered during the incompatible interaction between the cowpea genotype BRS-Marataoã and CPSMV. The leaf protein extracts from mock- (MI) and CPSMV-inoculated plantlets (V) were evaluated at 2 and 6days post-inoculation (DPI). Data support the assumptions that increases in biochemical (high hydrogen peroxide, antioxidant enzymes, and secondary compounds) and physiological responses (high photosynthesis index and chlorophyll content), confirmed by label-free comparative proteomic approach, in which quantitative changes in proteasome proteins, proteins related to photosynthesis, redox homeostasis, regulation factors/RNA processing proteins were observed may be implicated in the resistance of BRS-Marataoã to CPSMV. This pioneering study provides information for the selection of specific pathways and proteins, altered in this incompatible relationship, which could be chosen as targets for detailed studies to advance our understanding of the molecular, physiological, and biochemistry basis of the resistance mechanism of cowpea and design approachs to engineer plants that are more productive. This is a pioneering study in which an incompatible relationship between a resistant cowpea and Cowpea severe mosaic virus (CPSMV) was conducted to comparatively evaluate proteomic profiles by Gel-free/label-free methodology and some physiological and biochemical parameters to shed light on how a resistant cowpea cultivar deals with the virus attack. Specific proteins and associated pathways were altered in the cowpea plants challenged with CPSMV and will contribute to our knowledge on the biological process tailored by cowpea in response to CPSMV. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. [Analysis and research on the degradation and migration of organic pollutants in textile wastewater treatment process by GC-MS].

    PubMed

    Liu, Wei-jing; Zhang, Long; Wu, Wei; Tu, Yong

    2010-04-01

    In order to analyze the advantages/disadvantages of the combined treatment process between "physicochemical + biochemical" and "biochemical + physicochemical" in treatment of textile wastewater, gas chromatography-mass spectrometry (GC-MS) was used to determine the degradation process of organic pollutants in this two totally different treatment processes. The same analysis was also conducted to the sludge and discharged water. The results showed that the "physicochemical + biochemical" process displayed a poorer effect than "biochemical + physicochemical" in degrading the organic pollutants. The latter was 6.2% higher than the former in removing the organic pollutants averagely. The difference was mainly manifested in the efficiency of anaerobic hydrolysis in the two coupled processes. Moreover, the implement of "physicochemical + biochemical" process resulted in the migration of plenty of typical organic pollutants to sludge from primary coagulation sedimentation process and to the discharged water, which would cause secondary pollution easily.

  4. Novel Contrast Mechanisms at 3 Tesla and 7 Tesla

    PubMed Central

    Regatte, Ravinder R.; Schweitzer, Mark E.

    2013-01-01

    Osteoarthritis (OA) is the most common musculoskeletal degenerative disease, affecting millions of people. Although OA has been considered primarily a cartilage disorder associated with focal cartilage degeneration, it is accompanied by well-known changes in subchondral and trabecular bone, including sclerosis and osteophyte formation. The exact cause of OA initiation and progression remains under debate, but OA typically first affects weightbearing joints such as the knee. Magnetic resonance imaging (MRI) has been recognized as a potential tool for quantitative assessment of cartilage abnormalities due to its excellent soft tissue contrast. Over the last two decades, several new MR biochemical imaging methods have been developed to characterize the disease process and possibly predict the progression of knee OA. These new MR biochemical methods play an important role not only for diagnosis of disease at an early stage, but also for their potential use in monitoring outcome of various drug therapies (success or failure). Recent advances in multicoil radiofrequency technology and high field systems (3 T and above) significantly improve the sensitivity and specificity of imaging studies for the diagnosis of musculoskeletal disorders. The current state-of-the-art MR imaging methods are briefly reviewed for the quantitative biochemical and functional imaging assessment of musculoskeletal systems. PMID:18850506

  5. Traditional Chinese Biotechnology

    NASA Astrophysics Data System (ADS)

    Xu, Yan; Wang, Dong; Fan, Wen Lai; Mu, Xiao Qing; Chen, Jian

    The earliest industrial biotechnology originated in ancient China and developed into a vibrant industry in traditional Chinese liquor, rice wine, soy sauce, and vinegar. It is now a significant component of the Chinese economy valued annually at about 150 billion RMB. Although the production methods had existed and remained basically unchanged for centuries, modern developments in biotechnology and related fields in the last decades have greatly impacted on these industries and led to numerous technological innovations. In this chapter, the main biochemical processes and related technological innovations in traditional Chinese biotechnology are illustrated with recent advances in functional microbiology, microbial ecology, solid-state fermentation, enzymology, chemistry of impact flavor compounds, and improvements made to relevant traditional industrial facilities. Recent biotechnological advances in making Chinese liquor, rice wine, soy sauce, and vinegar are reviewed.

  6. Multi-enzyme logic network architectures for assessing injuries: digital processing of biomarkers.

    PubMed

    Halámek, Jan; Bocharova, Vera; Chinnapareddy, Soujanya; Windmiller, Joshua Ray; Strack, Guinevere; Chuang, Min-Chieh; Zhou, Jian; Santhosh, Padmanabhan; Ramirez, Gabriela V; Arugula, Mary A; Wang, Joseph; Katz, Evgeny

    2010-12-01

    A multi-enzyme biocatalytic cascade processing simultaneously five biomarkers characteristic of traumatic brain injury (TBI) and soft tissue injury (STI) was developed. The system operates as a digital biosensor based on concerted function of 8 Boolean AND logic gates, resulting in the decision about the physiological conditions based on the logic analysis of complex patterns of the biomarkers. The system represents the first example of a multi-step/multi-enzyme biosensor with the built-in logic for the analysis of complex combinations of biochemical inputs. The approach is based on recent advances in enzyme-based biocomputing systems and the present paper demonstrates the potential applicability of biocomputing for developing novel digital biosensor networks.

  7. Complexity and performance of on-chip biochemical assays

    NASA Astrophysics Data System (ADS)

    Kopf-Sill, Anne R.; Nikiforov, Theo; Bousse, Luc J.; Nagle, Rob; Parce, J. W.

    1997-03-01

    The use of microchips for performing biochemical processes has the potential to reduce reagent use and thus assay costs, increase throughput, and automate complex processes. We are building a multifunctional platform that provides sensing and actuation functions for a variety of microchip- based biochemical and analytical processes. Here we describe recent experiments that include on-chip dilution, reagent mixing, reaction, separation, and detection for important classes of biochemical assays. Issues in chip design and control are discussed.

  8. Protein Kinase C Activation Promotes Microtubule Advance in Neuronal Growth Cones by Increasing Average Microtubule Growth Lifetimes

    PubMed Central

    Kabir, Nurul; Schaefer, Andrew W.; Nakhost, Arash; Sossin, Wayne S.; Forscher, Paul

    2001-01-01

    We describe a novel mechanism for protein kinase C regulation of axonal microtubule invasion of growth cones. Activation of PKC by phorbol esters resulted in a rapid, robust advance of distal microtubules (MTs) into the F-actin rich peripheral domain of growth cones, where they are normally excluded. In contrast, inhibition of PKC activity by bisindolylmaleimide and related compounds had no perceptible effect on growth cone motility, but completely blocked phorbol ester effects. Significantly, MT advance occurred despite continued retrograde F-actin flow—a process that normally inhibits MT advance. Polymer assembly was necessary for PKC-mediated MT advance since it was highly sensitive to a range of antagonists at concentrations that specifically interfere with microtubule dynamics. Biochemical evidence is presented that PKC activation promotes formation of a highly dynamic MT pool. Direct assessment of microtubule dynamics and translocation using the fluorescent speckle microscopy microtubule marking technique indicates PKC activation results in a nearly twofold increase in the typical lifetime of a MT growth episode, accompanied by a 1.7-fold increase and twofold decrease in rescue and catastrophe frequencies, respectively. No significant effects on instantaneous microtubule growth, shortening, or sliding rates (in either anterograde or retrograde directions) were observed. MTs also spent a greater percentage of time undergoing retrograde transport after PKC activation, despite overall MT advance. These results suggest that regulation of MT assembly by PKC may be an important factor in determining neurite outgrowth and regrowth rates and may play a role in other cellular processes dependent on directed MT advance. PMID:11238458

  9. [Recent advance in chemotherapy for advanced colorectal cancer].

    PubMed

    Aiba, K

    1996-04-01

    Chemotherapy for advanced colorectal cancer is reviewed stressing the historical development of combination chemotherapy and the application of a new idea called biochemical modulation based upon a preclinical biochemical and molecular pharmacological rationale. While 5-fluorouracil (5-FU) is a key drug for more than three decades, many a combination chemotherapy with 5-FU and other drugs such as methyl-CCNU, vincristine, streptozocin, mitomycin C and so on has been studied extensively only to show no significant improvement compared with monotherapy with 5-FU. Recently, the mechanisms of 5-FU action have been recognized more in detail biochemically, and it enabled us to try the drug in a more optimal way. For example, bolus i.v. infusion of 5-FU can produce a response rate of around 10% to 15% at most for advanced colorectal cancer. On the other hand, a more continuous mode of i.v. infusion, typically known as protracted i.v. infusion lasting up to 6 weeks or more, can produce the response rate of up to 40%. The difference underlying the mechanisms of action in these typical two administrative methods is that the main target can be RNA-directed cytotoxicity in the bolus type infusion and it can be shifted toward DNA-directed cytotoxicity in the continuous type infusion through the inhibition of thymidylate synthase (TS) enzyme activity which is relevant to DNA de novo synthesis. More importantly, investigations using clinical materials imply that DNA-directed cytotoxicity may be more relevant in a clinical setting, showing consistent findings between bench-top experiments and the clinical outcome. Given a precise knowledge about the mechanisms of 5-FU action, we could have developed a new type combination chemotherapy called biochemical modulation which manipulates non-cytotoxic agents or cytotoxic agents in non-cytotoxic level as modulators enhancing cytotoxicity of 5-FU biochemically. Among modulators, leucovorin (LV) has been shown to have a pivotal role in this field. Although no optimal combination dose schedule of LV is well known, randomized studies have shown improved activity of 5-FU modulation by LV over 5-FU alone for advanced colorectal cancer doubled the response rate by monotherapy (20-25%) vs 10-15%). New drugs are also promising with the response rate of 25% approximately obtained with a new camptothecin derivative CPT-11, and a pure TS inhibitor, Tomudex in phase II trials. It is also necessary to explore the clinical activity of the combination of low-dose cisplatin and 5-FU, chronotherapy, new dihydropyrimidine dehydrogenase inhibitors and new TS inhibitors. We are facing a new era with a new treatment concept of biochemical modulation or an understanding of optimal administrative methods with the key drug, 5-FU. Obviously, we still seek new agents or new laboratory rationales which enable us to extend the survival of patients with advanced colorectal cancer.

  10. On brain lesions, the milkman and Sigmunda.

    PubMed

    Izquierdo, I; Medina, J H

    1998-10-01

    Lesion studies have been of historical importance in establishing the brain systems involved in memory processes. Many of those studies, however, have been overinterpreted in terms of the actual role of each system and of connections between systems. The more recent molecular pharmacological approach has produced major advances in these two areas. The main biochemical steps of memory formation in the CAI region of the hippocampus have been established by localized microinfusions of drugs acting on specific enzymes of receptors, by subcellular measurements of the activity or function of those enzymes and receptors at definite times, and by transgenic deletions or changes of those proteins. The biochemical steps of long-term memory formation in CAI have been found to be quite similar to those of long-term potentiation in the same region, and of other forms of plasticity. Connections between the hippocampus and the entorhinal and parietal cortices in the formation and modulation of short- and long-term memory have also been elucidated using these techniques. Lesion studies, coupled with imaging studies, still have a role to play; with regard to human memory, this role is in many ways unique. But these methods by themselves are not informative as to the mechanisms of memory processing, storage or modulation.

  11. A systematic petri net approach for multiple-scale modeling and simulation of biochemical processes.

    PubMed

    Chen, Ming; Hu, Minjie; Hofestädt, Ralf

    2011-06-01

    A method to exploit hybrid Petri nets for modeling and simulating biochemical processes in a systematic way was introduced. Both molecular biology and biochemical engineering aspects are manipulated. With discrete and continuous elements, the hybrid Petri nets can easily handle biochemical factors such as metabolites concentration and kinetic behaviors. It is possible to translate both molecular biological behavior and biochemical processes workflow into hybrid Petri nets in a natural manner. As an example, penicillin production bioprocess is modeled to illustrate the concepts of the methodology. Results of the dynamic of production parameters in the bioprocess were simulated and observed diagrammatically. Current problems and post-genomic perspectives were also discussed.

  12. New biochemical markers: from bench to bedside.

    PubMed

    Zaninotto, Martina; Mion, Monica Maria; Novello, Enrica; Altinier, Sara; Plebani, Mario

    2007-05-01

    Evaluation of patients presenting to hospital with chest pain or other signs or symptoms suggesting acute coronary syndrome (ACS) is problematic, time-consuming and sometimes expensive, even if new biochemical markers, such as troponins, have improved the ability to detect cardiac injury. However, patients with normal troponin values are not necessarily risk-free for major cardiac events. Recent investigations indicate that the overall patient risk may be assessed earlier than before, thanks to new knowledge acquired concerning the pathobiology of atherosclerosis and molecular events involved in the progression of disease, thus allowing the development of new biochemical markers. Some selected markers are released during the different phases of development of cardiovascular disease and may be useful for the diagnosis of patients with cardiovascular disease. In particular, the identification of emerging markers that provide relevant information on the inflammatory process, and the development of biomarkers whose circulating concentrations suggest the status of plaque instability and rupture, seems to be of particular value in prognosis and risk stratification. The overall expectations for a cardiovascular biochemical marker are not only its biological plausibility but also the availability at a reasonable cost of rapid, high quality assays, and their correct interpretation by clinicians using optimal cut-offs. The crossing from bench to bedside for each new marker discovered, must be associated with concurrent advances in the characterization of analytical features and the development of routine assay, in the assessment of analytical performance and in interpretative reporting of test results as well as in the training of physicians to use the array of biomarkers available appropriately and to interpret them correctly. This approach calls for the coordinated support of clinicians, technology experts, statisticians and the industry so that new biochemical developments can be of optimal value.

  13. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809

    PubMed Central

    Van Goor, Fredrick; Hadida, Sabine; Grootenhuis, Peter D. J.; Burton, Bill; Stack, Jeffrey H.; Straley, Kimberly S.; Decker, Caroline J.; Miller, Mark; McCartney, Jason; Olson, Eric R.; Wine, Jeffrey J.; Frizzell, Ray A.; Ashlock, Melissa; Negulescu, Paul A.

    2011-01-01

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that impair the function of CFTR, an epithelial chloride channel required for proper function of the lung, pancreas, and other organs. Most patients with CF carry the F508del CFTR mutation, which causes defective CFTR protein folding and processing in the endoplasmic reticulum, resulting in minimal amounts of CFTR at the cell surface. One strategy to treat these patients is to correct the processing of F508del-CFTR with small molecules. Here we describe the in vitro pharmacology of VX-809, a CFTR corrector that was advanced into clinical development for the treatment of CF. In cultured human bronchial epithelial cells isolated from patients with CF homozygous for F508del, VX-809 improved F508del-CFTR processing in the endoplasmic reticulum and enhanced chloride secretion to approximately 14% of non-CF human bronchial epithelial cells (EC50, 81 ± 19 nM), a level associated with mild CF in patients with less disruptive CFTR mutations. F508del-CFTR corrected by VX-809 exhibited biochemical and functional characteristics similar to normal CFTR, including biochemical susceptibility to proteolysis, residence time in the plasma membrane, and single-channel open probability. VX-809 was more efficacious and selective for CFTR than previously reported CFTR correctors. VX-809 represents a class of CFTR corrector that specifically addresses the underlying processing defect in F508del-CFTR. PMID:21976485

  14. Water-quality assessment and wastewater-management alternatives for Dardenne Creek in St Charles County, Missouri

    USGS Publications Warehouse

    Berkas, W.R.; Lodderhose, J.R.

    1985-01-01

    The quality of water in the 15 mile downstream reach of Dardenne Creek in St. Charles County, Missouri, was assessed to determine if it met the Missouri water quality standards. Concentrations of dissolved oxygen and total ammonia failed to meet water quality standards downstream from the Harvester-Dardenne and St. Peters Wastewater-Treatment Plants. The QUAL-II SEMCOG water quality model was calibrated and verified using two independent data sets from Dardenne Creek. Management alternatives using current, design capacity, and future expansion wastewater discharges from the St. Peters Wastewater-Treatment Plant were evaluated. Results of the computer simulation indicate that a nitrification-type advanced-treatment facility installed at the plant would produce a 5-day carbonaceous biochemical oxygen demand of 10 mg/L. An effluent limit of 5.0 mg/L of 5-day carbonaceous biochemical oxygen demand would further improve the water quality of Dardenne Creek; however, an additional treatment process, such as sand filtration, would be needed to meet this criterion. (USGS)

  15. Single molecule techniques in DNA repair: A primer

    PubMed Central

    Hughes, Craig D.; Simons, Michelle; Mackenzie, Cassidy E.; Van Houten, Bennett; Kad, Neil M.

    2016-01-01

    A powerful new approach has become much more widespread and offers insights into aspects of DNA repair unattainable with billions of molecules. Single molecule techniques can be used to image, manipulate or characterize the action of a single repair protein on a single strand of DNA. This allows search mechanisms to be probed, and the effects of force to be understood. These physical aspects can dominate a biochemical reaction, where at the ensemble level their nuances are obscured. In this paper we discuss some of the many technical advances that permit study at the single molecule level. We focus on DNA repair to which these techniques are actively being applied. DNA repair is also a process that encompasses so much of what single molecule studies benefit – searching for targets, complex formation, sequential biochemical reactions and substrate hand-off to name just a few. We discuss how single molecule biophysics is poised to transform our understanding of biological systems, in particular DNA repair. PMID:24819596

  16. 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.

  17. Understanding Cooperative Chirality at the Nanoscale

    NASA Astrophysics Data System (ADS)

    Yu, Shangjie; Wang, Pengpeng; Govorov, Alexander; Ouyang, Min

    Controlling chirality of organic and inorganic structures plays a key role in many physical, chemical and biochemical processes, and may offer new opportunity to create technology applications based on chiroptical effect. In this talk, we will present a theoretical model and simulation to demonstrate how to engineer nanoscale chirality in inorganic nanostructures via synergistic control of electromagnetic response of both lattice and geometry, leading to rich tunability of chirality at the nanoscale. Our model has also been applied to understand recent materials advancement of related control with excellent agreement, and can elucidate physical origins of circular dichroism features in the experiment.

  18. The Nucleosome Remodeling and Deacetylase (NuRD) Complex in Development and Disease

    PubMed Central

    Basta, Jeannine; Rauchman, Michael

    2014-01-01

    The Nucleosome Remodeling and Deacetylase (NuRD) complex is one of the major chromatin remodeling complexes found in cells. It plays an important role in regulating gene transcription, genome integrity and cell cycle progression. Through its impact on these basic cellular processes, increasing evidence indicates that alterations in the activity of this macromolecular complex can lead to developmental defects, oncogenesis and accelerated ageing. Recent genetic and biochemical studies have elucidated the mechanisms of NuRD action in modifying the chromatin landscape. These advances have the potential to lead to new therapeutic approaches to birth defects and cancer. PMID:24880148

  19. The impact of plant biotechnology on food allergy.

    PubMed

    Herman, Eliot M; Burks, A Wesley

    2011-04-01

    Concerns about food allergy and its societal growth are intertwined with the growing advances in plant biotechnology. The knowledge of plant genes and protein structures provides the key foundation to understanding biochemical processes that produce food allergy. Biotechnology offers the prospect of producing low-allergen or allergen null plants that could mitigate the allergic response. Modified low-IgE binding variants of allergens could be used as a vaccine to build immunotolerance in sensitive individuals. The potential to introduce new allergens into the food supply by biotechnology products is a regulatory concern. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. Cell Penetrating Bispecific Antibodies for Targeting Oncogenic Transcription Factors in Advanced Prostate Cancer

    DTIC Science & Technology

    2016-12-01

    biochemical and biologic assay systems. The final specific aim was tol examine the ability of the bispecific antibody to perturb the growth of prostate ...designated by other documentation. TITLE: Cell-Penetrating Bispecific Antibodies for Targeting Oncogenic Transcription Factors in Advanced Prostate ...Bispecific Antibodies for Targeting Oncogenic Transcription Factors in Advanced Prostate Cancer Michael Lilly, MD Richard Weisbart, MD Medical

  1. Towards Understanding Plant Calcium Signaling through Calmodulin-Like Proteins: A Biochemical and Structural Perspective.

    PubMed

    La Verde, Valentina; Dominici, Paola; Astegno, Alessandra

    2018-04-30

    Ca 2+ ions play a key role in a wide variety of environmental responses and developmental processes in plants, and several protein families with Ca 2+ -binding domains have evolved to meet these needs, including calmodulin (CaM) and calmodulin-like proteins (CMLs). These proteins have no catalytic activity, but rather act as sensor relays that regulate downstream targets. While CaM is well-studied, CMLs remain poorly characterized at both the structural and functional levels, even if they are the largest class of Ca 2+ sensors in plants. The major structural theme in CMLs consists of EF-hands, and variations in these domains are predicted to significantly contribute to the functional versatility of CMLs. Herein, we focus on recent advances in understanding the features of CMLs from biochemical and structural points of view. The analysis of the metal binding and structural properties of CMLs can provide valuable insight into how such a vast array of CML proteins can coexist, with no apparent functional redundancy, and how these proteins contribute to cellular signaling while maintaining properties that are distinct from CaM and other Ca 2+ sensors. An overview of the principal techniques used to study the biochemical properties of these interesting Ca 2+ sensors is also presented.

  2. p53 and PCNA expression in advanced colorectal cancer: response to chemotherapy and long-term prognosis.

    PubMed

    Paradiso, A; Rabinovich, M; Vallejo, C; Machiavelli, M; Romero, A; Perez, J; Lacava, J; Cuevas, M A; Rodriquez, R; Leone, B; Sapia, M G; Simone, G; De Lena, M

    1996-12-20

    In a series of 71 patients with advanced colorectal cancer treated with biochemically modulated 5-fluorouracil (5-FU) and methotrexate (MTX), we investigated the relationship between the proliferating-cell nuclear antigen (PCNA) (PC10) and p53 (Pab1801) primary-tumor immunohistochemical expression with respect to clinical response and long-term prognosis. Nuclear p53 expression was demonstrated in 44% of samples (any number of positive tumor cells) while all tumors showed a certain degree of PCNA immunostaining. PCNA immunostaining was correlated with histopathologic grade and p53 expression, while p53 was not correlated with any of the parameters considered. The probability of clinical response to biochemically modulated 5-FU was independent of p53 and PCNA expression. p53 expression (all cut-off values) was not associated with short- or long-term clinical prognosis, whereas patients with higher PCNA primary-tumor expression showed longer survival from treatment and survival from diagnosis, according to univariate and multivariate analysis, particularly in the sub-set of colon-cancer patients. We conclude that the clinical response of advanced-colorectal-cancer patients to biochemically modulated 5-FU and MTX cannot be predicted by PCNA and p53 primary-tumor expression, but high PCNA expression appears to be independently related to long-term prognosis.

  3. Structure and Function of the 26S Proteasome.

    PubMed

    Bard, Jared A M; Goodall, Ellen A; Greene, Eric R; Jonsson, Erik; Dong, Ken C; Martin, Andreas

    2018-06-20

    As the endpoint for the ubiquitin-proteasome system, the 26S proteasome is the principal proteolytic machine responsible for regulated protein degradation in eukaryotic cells. The proteasome's cellular functions range from general protein homeostasis and stress response to the control of vital processes such as cell division and signal transduction. To reliably process all the proteins presented to it in the complex cellular environment, the proteasome must combine high promiscuity with exceptional substrate selectivity. Recent structural and biochemical studies have shed new light on the many steps involved in proteasomal substrate processing, including recognition, deubiquitination, and ATP-driven translocation and unfolding. In addition, these studies revealed a complex conformational landscape that ensures proper substrate selection before the proteasome commits to processive degradation. These advances in our understanding of the proteasome's intricate machinery set the stage for future studies on how the proteasome functions as a major regulator of the eukaryotic proteome.

  4. Chemical kinetic mechanistic models to investigate cancer biology and impact cancer medicine.

    PubMed

    Stites, Edward C

    2013-04-01

    Traditional experimental biology has provided a mechanistic understanding of cancer in which the malignancy develops through the acquisition of mutations that disrupt cellular processes. Several drugs developed to target such mutations have now demonstrated clinical value. These advances are unequivocal testaments to the value of traditional cellular and molecular biology. However, several features of cancer may limit the pace of progress that can be made with established experimental approaches alone. The mutated genes (and resultant mutant proteins) function within large biochemical networks. Biochemical networks typically have a large number of component molecules and are characterized by a large number of quantitative properties. Responses to a stimulus or perturbation are typically nonlinear and can display qualitative changes that depend upon the specific values of variable system properties. Features such as these can complicate the interpretation of experimental data and the formulation of logical hypotheses that drive further research. Mathematical models based upon the molecular reactions that define these networks combined with computational studies have the potential to deal with these obstacles and to enable currently available information to be more completely utilized. Many of the pressing problems in cancer biology and cancer medicine may benefit from a mathematical treatment. As work in this area advances, one can envision a future where such models may meaningfully contribute to the clinical management of cancer patients.

  5. An integrated approach to coronary heart disease diagnosis and clinical management.

    PubMed

    Infante, Teresa; Forte, Ernesto; Schiano, Concetta; Cavaliere, Carlo; Tedeschi, Carlo; Soricelli, Andrea; Salvatore, Marco; Napoli, Claudio

    2017-01-01

    The major issue in coronary heart disease (CHD) diagnosis and management is that symptoms onset in an advanced state of disease. Despite the availability of several clinical risk scores, the prediction of cardiovascular events is lacking, and many patients at risk are not well stratified according to the canonical risk factors alone. Therefore, adequate risk assessment remains the most challenging issue. Recently, the integration of imaging data with biochemical markers in a radiogenomic framework has been proposed in many fields of medicine as well as in cardiology. Multimodal imaging and advanced processing techniques can provide both direct (e.g., remodeling index, calcium score, total plaque volume, plaque burden) and indirect (e.g., myocardial perfusion index, coronary flow reserve) imaging features of CHD. Furthermore, the identification of novel non-invasive biochemical markers, mainly focused on plasma and/or serum samples, has increased the specificity of findings, reflecting several pathophysiological pathways of atherosclerosis, the principal actor in CHD. In this context, a multifaced approach, derived from the strengths of all these modalities, appears promising for finer risk stratification and treatment strategies, facilitating the decision-making and clinical management of patients. This review underlines the role of different imaging modalities in the quantification of coronary atherosclerosis and describes novel blood-based markers that could improve diagnosis and have a better predictive value in CHD.

  6. Effects of advanced wastewater treatment on the quality of White River, Indiana

    USGS Publications Warehouse

    Crawford, Charles G.; Wangsness, David J.

    1991-01-01

    In 1983, the City of Indianapolis, Indiana, completed construction of advanced wastewater treatment (AWT) systems to enlarge and upgrade its existing Belmont Road and Southport Road secondary treatment plants. A nonparametric statistical procedure, a modified form of the Wilcoxon-Mann-Whitney rank-sum test, was used to test for trends in water quality at two upstream and two downstream sites on White River and at the two treatment plants. Results comparing the pre- (1978-1980) and post- (1983-1988) AWT periods show statistically significant improvements in the quality of the treated effluent and of the White River downstream from the plants. Water quality at sites upstream from the city was relatively constant during the period of study. Total ammonia (as N) decreased 14.6 mg/L and BOD5 (five-day biochemical oxygen demand) decreased 10 to 19 mg/L in the two effluents. Total ammonia in the river downstream from the plants decreased 0.8 to 1.9 mg/L and BOD5 decreased 2.3 to 2.5 mg/L. Nitrate (as N) increased 14.5 mg/L in the plant effluents and 2.0 to 2.4 mg/L in the river because of in-plant nitrification. Dissolved oxygen concentration in the river increased about 3 mg/L because of reduced oxygen demand for nitrification and biochemical oxidation processes.

  7. Molecular changes and signaling events occurring in sperm during epididymal maturation

    PubMed Central

    Gervasi, Maria Gracia; Visconti, Pablo E.

    2017-01-01

    After leaving the testis, sperm have not yet acquired the ability to move progressively and are unable to fertilize oocytes. To become fertilization-competent they must go through an epididymal maturation process in the male, and capacitation in the female tract. Epididymal maturation can be defined as those changes occurring to sperm in the epididymis that render the sperm the ability to capacitate in the female tract. As part of this process, sperm cells undergo a series of biochemical and physiological changes that require incorporation of new molecules derived from the epididymal epithelium, as well as post-translational modifications of endogenous proteins synthesized during spermiogenesis in the testis. This review will focus on epididymal maturation events, with emphasis in recent advances in the understanding of the molecular basis of this process. PMID:28297559

  8. Processes on the emergent landscapes of biochemical reaction networks and heterogeneous cell population dynamics: differentiation in living matters

    PubMed Central

    Li, Fangting

    2017-01-01

    The notion of an attractor has been widely employed in thinking about the nonlinear dynamics of organisms and biological phenomena as systems and as processes. The notion of a landscape with valleys and mountains encoding multiple attractors, however, has a rigorous foundation only for closed, thermodynamically non-driven, chemical systems, such as a protein. Recent advances in the theory of nonlinear stochastic dynamical systems and its applications to mesoscopic reaction networks, one reaction at a time, have provided a new basis for a landscape of open, driven biochemical reaction systems under sustained chemostat. The theory is equally applicable not only to intracellular dynamics of biochemical regulatory networks within an individual cell but also to tissue dynamics of heterogeneous interacting cell populations. The landscape for an individual cell, applicable to a population of isogenic non-interacting cells under the same environmental conditions, is defined on the counting space of intracellular chemical compositions x = (x1,x2, … ,xN) in a cell, where xℓ is the concentration of the ℓth biochemical species. Equivalently, for heterogeneous cell population dynamics xℓ is the number density of cells of the ℓth cell type. One of the insights derived from the landscape perspective is that the life history of an individual organism, which occurs on the hillsides of a landscape, is nearly deterministic and ‘programmed’, while population-wise an asynchronous non-equilibrium steady state resides mostly in the lowlands of the landscape. We argue that a dynamic ‘blue-sky’ bifurcation, as a representation of Waddington's landscape, is a more robust mechanism for a cell fate decision and subsequent differentiation than the widely pictured pitch-fork bifurcation. We revisit, in terms of the chemostatic driving forces upon active, living matter, the notions of near-equilibrium thermodynamic branches versus far-from-equilibrium states. The emergent landscape perspective permits a quantitative discussion of a wide range of biological phenomena as nonlinear, stochastic dynamics. PMID:28490602

  9. The developing framework of marine ecotoxicology: Pollutants as a variable in marine ecosystems?

    USGS Publications Warehouse

    Luoma, Samuel N.

    1996-01-01

    Marine ecosystems include a subset in which at least some interrelated geochemical, biochemical, physiological, population and community characteristics are changed by pollutants. Moderate contamination is relatively widespread in coastal and estuarine ecosystems, so the subset of ecosystems with at least some processes affected could be relatively large. Pollutant influences have changed and will probably continue to change on time scales of decades. Biological exposures and dose in such ecosystems are species-specific and determined by how the species is exposed to different environmental media and the geochemistry of individual pollutants within those media. Bioaccumulation models offer significant promise for interpreting such exposures. Biological responses to pollutants need to be more directly linked to exposure and dose. At the level of the individual this might be improved by better understanding relationships between tissue concentrations of pollutants and responses to pollutants. Multi-discipline field and laboratory studies combined with advanced understanding of some basic processes have reduced the ambiguities in interpreting a few physiological/organismic responses to pollutants in nature. Recognition of pollutant-induced patterns in population responses could lead to similar advances. A rational framework for ecotoxicology is developing, but its further advance is dependent upon better integration of ecotoxicology with basic marine ecology and biology.

  10. Analytical considerations and dimensionless analysis for a description of particle interactions in high pressure processes

    NASA Astrophysics Data System (ADS)

    Rauh, Cornelia; Delgado, Antonio

    2010-12-01

    High pressures of up to several hundreds of MPa are utilized in a wide range of applications in chemical, bio-, and food engineering, aiming at selective control of (bio-)chemical reactions. Non-uniformity of process conditions may threaten the safety and quality of the resulting products because processing conditions such as pressure, temperature, and treatment history are crucial for the course of (bio-)chemical reactions. Therefore, thermofluid-dynamical phenomena during the high pressure process have to be examined, and numerical tools to predict process uniformity and to optimize the processes have to be developed. Recently applied mathematical models and numerical simulations of laboratory and industrial scale high pressure processes investigating the mentioned crucial phenomena are based on continuum balancing models of thermofluid dynamics. Nevertheless, biological systems are complex fluids containing the relevant (bio-)chemical compounds (enzymes and microorganisms). These compounds are particles that interact with the surrounding medium and between each other. This contribution deals with thermofluid-dynamical interactions of the relevant particulate (bio-)chemical compounds (enzymes and microorganisms) with the surrounding fluid. By consideration of characteristic time and length scales and particle forces, the motion of the (bio-)chemical compounds is characterized.

  11. Mitochondria, Cybrids, Aging, and Alzheimer’s Disease

    PubMed Central

    Swerdlow, Russell H.; Koppel, Scott; Weidling, Ian; Hayley, Clay; Ji, Yan; Wilkins, Heather M.

    2018-01-01

    Mitochondrial and bioenergetic function change with advancing age and may drive aging phenotypes. Mitochondrial and bioenergetic changes are also documented in various age-related neurodegenerative diseases, including Alzheimer’s disease (AD). In some instances AD mitochondrial and bioenergetic changes are reminiscent of those observed with advancing age, but are greater in magnitude. Mitochondrial and bioenergetic dysfunction could, therefore, link neurodegeneration to brain aging. Interestingly, mitochondrial defects in AD patients are not brain-limited, and mitochondrial function can be linked to classic AD histologic changes including amyloid precursor protein processing to beta amyloid. Also, transferring mitochondria from AD subjects to cell lines depleted of endogenous mitochondrial DNA (mtDNA) creates cytoplasmic hybrid (cybrid) cell lines that recapitulate specific biochemical, molecular, and histologic AD features. Such findings have led to the formulation of a “mitochondrial cascade hypothesis” that places mitochondrial dysfunction at the apex of the AD pathology pyramid. Data pertinent to this premise are reviewed. PMID:28253988

  12. Preprinting Microbiology

    PubMed Central

    2017-01-01

    ABSTRACT The field of microbiology has experienced significant growth due to transformative advances in technology and the influx of scientists driven by a curiosity to understand how microbes sustain myriad biochemical processes that maintain Earth. With this explosion in scientific output, a significant bottleneck has been the ability to rapidly disseminate new knowledge to peers and the public. Preprints have emerged as a tool that a growing number of microbiologists are using to overcome this bottleneck. Posting preprints can help to transparently recruit a more diverse pool of reviewers prior to submitting to a journal for formal peer review. Although the use of preprints is still limited in the biological sciences, early indications are that preprints are a robust tool that can complement and enhance peer-reviewed publications. As publishing moves to embrace advances in Internet technology, there are many opportunities for preprints and peer-reviewed journals to coexist in the same ecosystem. PMID:28536284

  13. Preprinting Microbiology.

    PubMed

    Schloss, Patrick D

    2017-05-23

    The field of microbiology has experienced significant growth due to transformative advances in technology and the influx of scientists driven by a curiosity to understand how microbes sustain myriad biochemical processes that maintain Earth. With this explosion in scientific output, a significant bottleneck has been the ability to rapidly disseminate new knowledge to peers and the public. Preprints have emerged as a tool that a growing number of microbiologists are using to overcome this bottleneck. Posting preprints can help to transparently recruit a more diverse pool of reviewers prior to submitting to a journal for formal peer review. Although the use of preprints is still limited in the biological sciences, early indications are that preprints are a robust tool that can complement and enhance peer-reviewed publications. As publishing moves to embrace advances in Internet technology, there are many opportunities for preprints and peer-reviewed journals to coexist in the same ecosystem. Copyright © 2017 Schloss.

  14. BNDB - the Biochemical Network Database.

    PubMed

    Küntzer, Jan; Backes, Christina; Blum, Torsten; Gerasch, Andreas; Kaufmann, Michael; Kohlbacher, Oliver; Lenhof, Hans-Peter

    2007-10-02

    Technological advances in high-throughput techniques and efficient data acquisition methods have resulted in a massive amount of life science data. The data is stored in numerous databases that have been established over the last decades and are essential resources for scientists nowadays. However, the diversity of the databases and the underlying data models make it difficult to combine this information for solving complex problems in systems biology. Currently, researchers typically have to browse several, often highly focused, databases to obtain the required information. Hence, there is a pressing need for more efficient systems for integrating, analyzing, and interpreting these data. The standardization and virtual consolidation of the databases is a major challenge resulting in a unified access to a variety of data sources. We present the Biochemical Network Database (BNDB), a powerful relational database platform, allowing a complete semantic integration of an extensive collection of external databases. BNDB is built upon a comprehensive and extensible object model called BioCore, which is powerful enough to model most known biochemical processes and at the same time easily extensible to be adapted to new biological concepts. Besides a web interface for the search and curation of the data, a Java-based viewer (BiNA) provides a powerful platform-independent visualization and navigation of the data. BiNA uses sophisticated graph layout algorithms for an interactive visualization and navigation of BNDB. BNDB allows a simple, unified access to a variety of external data sources. Its tight integration with the biochemical network library BN++ offers the possibility for import, integration, analysis, and visualization of the data. BNDB is freely accessible at http://www.bndb.org.

  15. Improving Marine Ecosystem Models with Biochemical Tracers

    NASA Astrophysics Data System (ADS)

    Pethybridge, Heidi R.; Choy, C. Anela; Polovina, Jeffrey J.; Fulton, Elizabeth A.

    2018-01-01

    Empirical data on food web dynamics and predator-prey interactions underpin ecosystem models, which are increasingly used to support strategic management of marine resources. These data have traditionally derived from stomach content analysis, but new and complementary forms of ecological data are increasingly available from biochemical tracer techniques. Extensive opportunities exist to improve the empirical robustness of ecosystem models through the incorporation of biochemical tracer data and derived indices, an area that is rapidly expanding because of advances in analytical developments and sophisticated statistical techniques. Here, we explore the trophic information required by ecosystem model frameworks (species, individual, and size based) and match them to the most commonly used biochemical tracers (bulk tissue and compound-specific stable isotopes, fatty acids, and trace elements). Key quantitative parameters derived from biochemical tracers include estimates of diet composition, niche width, and trophic position. Biochemical tracers also provide powerful insight into the spatial and temporal variability of food web structure and the characterization of dominant basal and microbial food web groups. A major challenge in incorporating biochemical tracer data into ecosystem models is scale and data type mismatches, which can be overcome with greater knowledge exchange and numerical approaches that transform, integrate, and visualize data.

  16. New advances in probing cell–extracellular matrix interactions

    PubMed Central

    2017-01-01

    The extracellular matrix (ECM) provides structural and biochemical support to cells within tissues. An emerging body of evidence has established that the ECM plays a key role in cell mechanotransduction – the study of coupling between mechanical inputs and cellular phenotype – through either mediating transmission of forces to the cells, or presenting mechanical cues that guide cellular behaviors. Recent progress in cell mechanotransduction research has been facilitated by advances of experimental tools, particularly microtechnologies, engineered biomaterials, and imaging and analytical methods. Microtechnologies have enabled the design and fabrication of controlled physical microenvironments for the study and measurement of cell–ECM interactions. Advances in engineered biomaterials have allowed researchers to develop synthetic ECMs that mimic tissue microenvironments and investigate the impact of altered physicochemical properties on various cellular processes. Finally, advanced imaging and spectroscopy techniques have facilitated the visualization of the complex interaction between cells and ECM in vitro and in living tissues. This review will highlight the application of recent innovations in these areas to probing cell–ECM interactions. We believe cross-disciplinary approaches, combining aspects of the different technologies reviewed here, will inspire innovative ideas to further elucidate the secrets of ECM-mediated cell control. PMID:28352896

  17. Advanced morphological and biochemical magnetic resonance imaging of cartilage repair procedures in the knee joint at 3 Tesla.

    PubMed

    Welsch, Goetz H; Mamisch, Tallal C; Hughes, Timothy; Domayer, Stephan; Marlovits, Stefan; Trattnig, Siegfried

    2008-09-01

    Morphological and biochemical magnetic resonance imaging (MRI) is due to high field MR systems, advanced coil technology, and sophisticated sequence protocols capable of visualizing articular cartilage in vivo with high resolution in clinical applicable scan time. Several conventional two-dimensional (2D) and three-dimensional (3D) approaches show changes in cartilage structure. Furthermore newer isotropic 3D sequences show great promise in improving cartilage imaging and additionally in diagnosing surrounding pathologies within the knee joint. Functional MR approaches are additionally able to provide a specific measure of the composition of cartilage. Cartilage physiology and ultra-structure can be determined, changes in cartilage macromolecules can be detected, and cartilage repair tissue can thus be assessed and potentially differentiated. In cartilage defects and following nonsurgical and surgical cartilage repair, morphological MRI provides the basis for diagnosis and follow-up evaluation, whereas biochemical MRI provides a deeper insight into the composition of cartilage and cartilage repair tissue. A combination of both, together with clinical evaluation, may represent a desirable multimodal approach in the future, also available in routine clinical use.

  18. Recent Advances in Transferable Coarse-Grained Modeling of Proteins

    PubMed Central

    Kar, Parimal; Feig, Michael

    2017-01-01

    Computer simulations are indispensable tools for studying the structure and dynamics of biological macromolecules. Biochemical processes occur on different scales of length and time. Atomistic simulations cannot cover the relevant spatiotemporal scales at which the cellular processes occur. To address this challenge, coarse-grained (CG) modeling of the biological systems are employed. Over the last few years, many CG models for proteins continue to be developed. However, many of them are not transferable with respect to different systems and different environments. In this review, we discuss those CG protein models that are transferable and that retain chemical specificity. We restrict ourselves to CG models of soluble proteins only. We also briefly review recent progress made in the multi-scale hybrid all-atom/coarse-grained simulations of proteins. PMID:25443957

  19. Advances in enhanced biological phosphorus removal: from micro to macro scale.

    PubMed

    Oehmen, Adrian; Lemos, Paulo C; Carvalho, Gilda; Yuan, Zhiguo; Keller, Jürg; Blackall, Linda L; Reis, Maria A M

    2007-06-01

    The enhanced biological phosphorus removal (EBPR) process has been implemented in many wastewater treatment plants worldwide. While the EBPR process is indeed capable of efficient phosphorus (P) removal performance, disturbances and prolonged periods of insufficient P removal have been observed at full-scale plants on numerous occasions under conditions that are seemingly favourable for EBPR. Recent studies in this field have utilised a wide range of approaches to address this problem, from studying the microorganisms that are primarily responsible for or detrimental to this process, to determining their biochemical pathways and developing mathematical models that facilitate better prediction of process performance. The overall goal of each of these studies is to obtain a more detailed insight into how the EBPR process works, where the best way of achieving this objective is through linking together the information obtained using these different approaches. This review paper critically assesses the recent advances that have been achieved in this field, particularly relating to the areas of EBPR microbiology, biochemistry, process operation and process modelling. Potential areas for future research are also proposed. Although previous research in this field has undoubtedly improved our level of understanding, it is clear that much remains to be learned about the process, as many unanswered questions still remain. One of the challenges appears to be the integration of the existing and growing scientific knowledge base with the observations and applications in practice, which this paper hopes to partially achieve.

  20. [Dinitrosyl iron complexes are endogenous signaling agents in animal and human cells and tissues (a hypothesis)].

    PubMed

    Vanin, A F

    2004-01-01

    The hypothesis was advanced that dinitrosyl iron complexes generated in animal and human cells and tissues producing nitric oxide can function as endogenous universal regulators of biochemical and physiological processes. This function is realized by the ability of dinitrosyl iron complexes to act as donors of free nitric oxide molecules interacting with the heme groups of proteins, nitrosonium ions, or Fe+(NO+)2 interacting with the thiol groups of proteins. The effect of dinitrosyl iron complexes on the activity of some enzymes and the expression of the genome at the translation and transcription levels was considered.

  1. Biochemicals from food waste and recalcitrant biomass via syngas fermentation: A review.

    PubMed

    Wainaina, Steven; Horváth, Ilona Sárvári; Taherzadeh, Mohammad J

    2018-01-01

    An effective method for the production of value-added chemicals from food waste and lignocellulosic materials is a hybrid thermal-biological process, which involves gasification of the solid materials to syngas (primarily CO and H 2 ) followed by fermentation. This paper reviews the recent advances in this process. The special focus is on the cultivation methods that involve the use of single strains, defined mixed cultures and undefined mixed cultures for production of carboxylic acids and higher alcohols. A rate limiting step in these processes is the low mass transfer between the gas and the liquid phases. Therefore, novel techniques that can enhance the gas-liquid mass transfer including membrane- and trickle-bed bioreactors were discussed. Such bioreactors have shown promising results in increasing the volumetric mass transfer coefficient (k L a). High gas pressure also influences the mass transfer in certain batch processes, although the presence of impurities in the gas would impede the process. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Optical Fiber Sensing Using Quantum Dots

    PubMed Central

    Jorge, Pedro; Martins, Manuel António; Trindade, Tito; Santos, José Luís; Farahi, Faramarz

    2007-01-01

    Recent advances in the application of semiconductor nanocrystals, or quantum dots, as biochemical sensors are reviewed. Quantum dots have unique optical properties that make them promising alternatives to traditional dyes in many luminescence based bioanalytical techniques. An overview of the more relevant progresses in the application of quantum dots as biochemical probes is addressed. Special focus will be given to configurations where the sensing dots are incorporated in solid membranes and immobilized in optical fibers or planar waveguide platforms. PMID:28903308

  3. In search of cellular control: signal transduction in context

    NASA Technical Reports Server (NTRS)

    Ingber, D.

    1998-01-01

    The field of molecular cell biology has experienced enormous advances over the last century by reducing the complexity of living cells into simpler molecular components and binding interactions that are amenable to rigorous biochemical analysis. However, as our tools become more powerful, there is a tendency to define mechanisms by what we can measure. The field is currently dominated by efforts to identify the key molecules and sequences that mediate the function of critical receptors, signal transducers, and molecular switches. Unfortunately, these conventional experimental approaches ignore the importance of supramolecular control mechanisms that play a critical role in cellular regulation. Thus, the significance of individual molecular constituents cannot be fully understood when studied in isolation because their function may vary depending on their context within the structural complexity of the living cell. These higher-order regulatory mechanisms are based on the cell's use of a form of solid-state biochemistry in which molecular components that mediate biochemical processing and signal transduction are immobilized on insoluble cytoskeletal scaffolds in the cytoplasm and nucleus. Key to the understanding of this form of cellular regulation is the realization that chemistry is structure and hence, recognition of the the importance of architecture and mechanics for signal integration and biochemical control. Recent work that has unified chemical and mechanical signaling pathways provides a glimpse of how this form of higher-order cellular control may function and where paths may lie in the future.

  4. Cooperative ethylene receptor signaling

    PubMed Central

    Liu, Qian; Wen, Chi-Kuang

    2012-01-01

    The gaseous plant hormone ethylene is perceived by a family of five ethylene receptor members in the dicotyledonous model plant Arabidopsis. Genetic and biochemical studies suggest that the ethylene response is suppressed by ethylene receptor complexes, but the biochemical nature of the receptor signal is unknown. Without appropriate biochemical measures to trace the ethylene receptor signal and quantify the signal strength, the biological significance of the modulation of ethylene responses by multiple ethylene receptors has yet to be fully addressed. Nevertheless, the ethylene receptor signal strength can be reflected by degrees in alteration of various ethylene response phenotypes and in expression levels of ethylene-inducible genes. This mini-review highlights studies that have advanced our understanding of cooperative ethylene receptor signaling. PMID:22827938

  5. Response and adaptation of photosynthesis, respiration, and antioxidant systems to elevated CO2 with environmental stress in plants

    PubMed Central

    Xu, Zhenzhu; Jiang, Yanling; Zhou, Guangsheng

    2015-01-01

    It is well known that plant photosynthesis and respiration are two fundamental and crucial physiological processes, while the critical role of the antioxidant system in response to abiotic factors is still a focus point for investigating physiological stress. Although one key metabolic process and its response to climatic change have already been reported and reviewed, an integrative review, including several biological processes at multiple scales, has not been well reported. The current review will present a synthesis focusing on the underlying mechanisms in the responses to elevated CO2 at multiple scales, including molecular, cellular, biochemical, physiological, and individual aspects, particularly, for these biological processes under elevated CO2 with other key abiotic stresses, such as heat, drought, and ozone pollution, as well as nitrogen limitation. The present comprehensive review may add timely and substantial information about the topic in recent studies, while it presents what has been well established in previous reviews. First, an outline of the critical biological processes, and an overview of their roles in environmental regulation, is presented. Second, the research advances with regard to the individual subtopics are reviewed, including the response and adaptation of the photosynthetic capacity, respiration, and antioxidant system to CO2 enrichment alone, and its combination with other climatic change factors. Finally, the potential applications for plant responses at various levels to climate change are discussed. The above issue is currently of crucial concern worldwide, and this review may help in a better understanding of how plants deal with elevated CO2 using other mainstream abiotic factors, including molecular, cellular, biochemical, physiological, and whole individual processes, and the better management of the ecological environment, climate change, and sustainable development. PMID:26442017

  6. Ryan Davis | NREL

    Science.gov Websites

    design TEA LCA Biochemical conversion process pathways Algal biomass production and conversion pathways Production," Green Chemistry (2015) Process Design and Economics for the Conversion of Lignocellulosic Production," Applied Energy (2011) Process Design and Economics for Biochemical Conversion of

  7. Live Cell Genomics: RNA Exon-Specific RNA-Binding Protein Isolation.

    PubMed

    Bell, Thomas J; Eberwine, James

    2015-01-01

    RNA-binding proteins (RBPs) are essential regulatory proteins that control all modes of RNA processing and regulation. New experimental approaches to isolate these indispensable proteins under in vivo conditions are needed to advance the field of RBP biology. Historically, in vitro biochemical approaches to isolate RBP complexes have been useful and productive, but biological relevance of the identified RBP complexes can be imprecise or erroneous. Here we review an inventive experimental to isolate RBPs under the in vivo conditions. The method is called peptide nucleic acid (PNA)-assisted identification of RBP (PAIR) technology and it uses cell-penetrating peptides (CPPs) to deliver photo-activatible RBP-capture molecule to the cytoplasm of the live cells. The PAIR methodology provides two significant advantages over the most commonly used approaches: (1) it overcomes the in vitro limitation of standard biochemical approaches and (2) the PAIR RBP-capture molecule is highly selective and adaptable which allows investigators to isolate exon-specific RBP complexes. Most importantly, the in vivo capture conditions and selectivity of the RBP-capture molecule yield biologically accurate and relevant RBP data.

  8. Research advances in major cereal crops for adaptation to abiotic stresses

    PubMed Central

    Maiti, RK; Satya, Pratik

    2014-01-01

    With devastating increase in population there is a great necessity to increase crop productivity of staple crops but the productivity is greatly affected by various abiotic stress factors such as drought, salinity. An attempt has been made a brief account on abiotic stress resistance of major cereal crops viz. In spite of good successes obtained on physiological and use molecular biology, the benefits of this high cost technology are beyond the reach of developing countries. This review discusses several morphological, anatomical, physiological, biochemical and molecular mechanisms of major cereal crops related to the adaptation of these crop to abiotic stress factors. It discusses the effect of abiotic stresses on physiological processes such as flowering, grain filling and maturation and plant metabolisms viz. photosynthesis, enzyme activity, mineral nutrition, and respiration. Though significant progress has been attained on the physiological, biochemical basis of resistance to abiotic stress factors, very little progress has been achieved to increase productivity under sustainable agriculture. Therefore, there is a great necessity of inter-disciplinary research to address this issue and to evolve efficient technology and its transfer to the farmers’ fields. PMID:25523172

  9. Biochemical and Molecular Mechanisms of Plant-Microbe-Metal Interactions: Relevance for Phytoremediation

    PubMed Central

    Ma, Ying; Oliveira, Rui S.; Freitas, Helena; Zhang, Chang

    2016-01-01

    Plants and microbes coexist or compete for survival and their cohesive interactions play a vital role in adapting to metalliferous environments, and can thus be explored to improve microbe-assisted phytoremediation. Plant root exudates are useful nutrient and energy sources for soil microorganisms, with whom they establish intricate communication systems. Some beneficial bacteria and fungi, acting as plant growth promoting microorganisms (PGPMs), may alleviate metal phytotoxicity and stimulate plant growth indirectly via the induction of defense mechanisms against phytopathogens, and/or directly through the solubilization of mineral nutrients (nitrogen, phosphate, potassium, iron, etc.), production of plant growth promoting substances (e.g., phytohormones), and secretion of specific enzymes (e.g., 1-aminocyclopropane-1-carboxylate deaminase). PGPM can also change metal bioavailability in soil through various mechanisms such as acidification, precipitation, chelation, complexation, and redox reactions. This review presents the recent advances and applications made hitherto in understanding the biochemical and molecular mechanisms of plant–microbe interactions and their role in the major processes involved in phytoremediation, such as heavy metal detoxification, mobilization, immobilization, transformation, transport, and distribution. PMID:27446148

  10. The Role of Electron Microscopy in Studying the Continuum of Changes in Membranous Structures during Poliovirus Infection

    PubMed Central

    Rossignol, Evan D.; Yang, Jie E.; Bullitt, Esther

    2015-01-01

    Replication of the poliovirus genome is localized to cytoplasmic replication factories that are fashioned out of a mixture of viral proteins, scavenged cellular components, and new components that are synthesized within the cell due to viral manipulation/up-regulation of protein and phospholipid synthesis. These membranous replication factories are quite complex, and include markers from multiple cytoplasmic cellular organelles. This review focuses on the role of electron microscopy in advancing our understanding of poliovirus RNA replication factories. Structural data from the literature provide the basis for interpreting a wide range of biochemical studies that have been published on virus-induced lipid biosynthesis. In combination, structural and biochemical experiments elucidate the dramatic membrane remodeling that is a hallmark of poliovirus infection. Temporal and spatial membrane modifications throughout the infection cycle are discussed. Early electron microscopy studies of morphological changes following viral infection are re-considered in light of more recent data on viral manipulation of lipid and protein biosynthesis. These data suggest the existence of distinct subcellular vesicle populations, each of which serves specialized roles in poliovirus replication processes. PMID:26473912

  11. Research advances in major cereal crops for adaptation to abiotic stresses.

    PubMed

    Maiti, R K; Satya, Pratik

    2014-01-01

    With devastating increase in population there is a great necessity to increase crop productivity of staple crops but the productivity is greatly affected by various abiotic stress factors such as drought, salinity. An attempt has been made a brief account on abiotic stress resistance of major cereal crops viz. In spite of good successes obtained on physiological and use molecular biology, the benefits of this high cost technology are beyond the reach of developing countries. This review discusses several morphological, anatomical, physiological, biochemical and molecular mechanisms of major cereal crops related to the adaptation of these crop to abiotic stress factors. It discusses the effect of abiotic stresses on physiological processes such as flowering, grain filling and maturation and plant metabolisms viz. photosynthesis, enzyme activity, mineral nutrition, and respiration. Though significant progress has been attained on the physiological, biochemical basis of resistance to abiotic stress factors, very little progress has been achieved to increase productivity under sustainable agriculture. Therefore, there is a great necessity of inter-disciplinary research to address this issue and to evolve efficient technology and its transfer to the farmers' fields.

  12. Investigating the biochemical progression of liver disease through fibrosis, cirrhosis, dysplasia, and hepatocellular carcinoma using Fourier transform infrared spectroscopic imaging

    NASA Astrophysics Data System (ADS)

    Sreedhar, Hari; Pant, Mamta; Ronquillo, Nemencio R.; Davidson, Bennett; Nguyen, Peter; Chennuri, Rohini; Choi, Jacqueline; Herrera, Joaquin A.; Hinojosa, Ana C.; Jin, Ming; Kajdacsy-Balla, Andre; Guzman, Grace; Walsh, Michael J.

    2014-03-01

    Hepatocellular carcinoma (HCC) is the most common form of primary hepatic carcinoma. HCC ranks the fourth most prevalent malignant tumor and the third leading cause of cancer related death in the world. Hepatocellular carcinoma develops in the context of chronic liver disease and its evolution is characterized by progression through intermediate stages to advanced disease and possibly even death. The primary sequence of hepatocarcinogenesis includes the development of cirrhosis, followed by dysplasia, and hepatocellular carcinoma.1 We addressed the utility of Fourier Transform Infrared (FT-IR) spectroscopic imaging, both as a diagnostic tool of the different stages of the disease and to gain insight into the biochemical process associated with disease progression. Tissue microarrays were obtained from the University of Illinois at Chicago tissue bank consisting of liver explants from 12 transplant patients. Tissue core biopsies were obtained from each explant targeting regions of normal, liver cell dysplasia including large cell change and small cell change, and hepatocellular carcinoma. We obtained FT-IR images of these tissues using a modified FT-IR system with high definition capabilities. Firstly, a supervised spectral classifier was built to discriminate between normal and cancerous hepatocytes. Secondly, an expanded classifier was built to discriminate small cell and large cell changes in liver disease. With the emerging advances in FT-IR instrumentation and computation there is a strong drive to develop this technology as a powerful adjunct to current histopathology approaches to improve disease diagnosis and prognosis.

  13. Diagnosis of sarcoidosis

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

    Sharma, O.P.

    1983-07-01

    During the last decade, many biochemical and immunologic advances have been made in the treatment and understanding of sarcoidosis. These studies have helped us to understand the basic mechanisms involved in granuloma formation, and many clinicians have used the information to diagnose and assess the activity of sarcoidosis. Further studies are needed to clearly establish the role of these advances in the everyday management of patients with sarcoidosis.

  14. Advances in the Application of Designed Ankyrin Repeat Proteins (DARPins) as Research Tools and Protein Therapeutics.

    PubMed

    Boersma, Ykelien L

    2018-01-01

    Nonimmunoglobulin scaffolds have been developed to overcome the limitations of monoclonal antibodies with regard to stability and size. Of these scaffolds, the class of designed ankyrin repeat proteins (DARPins) has advanced the most in biochemical and biomedical applications. This review focuses on the recent progress in DARPin technology, highlighting the scaffold's potential and possibilities.

  15. Biomarkers of a five-domain translational substrate for schizophrenia and schizoaffective psychosis.

    PubMed

    Fryar-Williams, Stephanie; Strobel, Jörg E

    2015-01-01

    The Mental Health Biomarker Project (2010-2014) selected commercial biochemistry markers related to monoamine synthesis and metabolism and measures of visual and auditory processing performance. Within a case-control discovery design with exclusion criteria designed to produce a highly characterised sample, results from 67 independently DSM IV-R-diagnosed cases of schizophrenia and schizoaffective disorder were compared with those from 67 control participants selected from a local hospital, clinic and community catchment area. Participants underwent protocol-based diagnostic-checking, functional-rating, biological sample-collection for thirty candidate markers and sensory-processing assessment. Fifteen biomarkers were identified on ROC analysis. Using these biomarkers, odds ratios, adjusted for a case-control design, indicated that schizophrenia and schizoaffective disorder were highly associated with dichotic listening disorder, delayed visual processing, low visual span, delayed auditory speed of processing, low reverse digit span as a measure of auditory working memory and elevated levels of catecholamines. Other nutritional and biochemical biomarkers were identified as elevated hydroxyl pyrroline-2-one as a marker of oxidative stress, vitamin D, B6 and folate deficits with elevation of serum B12 and free serum copper to zinc ratio. When individual biomarkers were ranked by odds ratio and correlated with clinical severity, five functional domains of visual processing, auditory processing, oxidative stress, catecholamines and nutritional-biochemical variables were formed. When the strengths of their inter-domain relationships were predicted by Lowess (non-parametric) regression, predominant bidirectional relationships were found between visual processing and catecholamine domains. At a cellular level, the nutritional-biochemical domain exerted a pervasive influence on the auditory domain as well as on all other domains. The findings of this biomarker research point towards a much-required advance in Psychiatry: quantification of some theoretically-understandable, translationally-informative, treatment-relevant underpinnings of serious mental illness. This evidence reveals schizophrenia and schizoaffective disorder in a somewhat different manner, as a conglomerate of several disorders many of which are not currently being assessed-for or treated in clinical settings. Currently available remediation techniques for these underlying conditions have potential to reduce treatment-resistance, relapse-prevention, cost burden and social stigma in these conditions. If replicated and validated in prospective trials, such findings will improve progress-monitoring and treatment-response for schizophrenia and schizoaffective disorder.

  16. Biochemical adaptation to ocean acidification.

    PubMed

    Stillman, Jonathon H; Paganini, Adam W

    2015-06-01

    The change in oceanic carbonate chemistry due to increased atmospheric PCO2  has caused pH to decline in marine surface waters, a phenomenon known as ocean acidification (OA). The effects of OA on organisms have been shown to be widespread among diverse taxa from a wide range of habitats. The majority of studies of organismal response to OA are in short-term exposures to future levels of PCO2 . From such studies, much information has been gathered on plastic responses organisms may make in the future that are beneficial or harmful to fitness. Relatively few studies have examined whether organisms can adapt to negative-fitness consequences of plastic responses to OA. We outline major approaches that have been used to study the adaptive potential for organisms to OA, which include comparative studies and experimental evolution. Organisms that inhabit a range of pH environments (e.g. pH gradients at volcanic CO2 seeps or in upwelling zones) have great potential for studies that identify adaptive shifts that have occurred through evolution. Comparative studies have advanced our understanding of adaptation to OA by linking whole-organism responses with cellular mechanisms. Such optimization of function provides a link between genetic variation and adaptive evolution in tuning optimal function of rate-limiting cellular processes in different pH conditions. For example, in experimental evolution studies of organisms with short generation times (e.g. phytoplankton), hundreds of generations of growth under future conditions has resulted in fixed differences in gene expression related to acid-base regulation. However, biochemical mechanisms for adaptive responses to OA have yet to be fully characterized, and are likely to be more complex than simply changes in gene expression or protein modification. Finally, we present a hypothesis regarding an unexplored area for biochemical adaptation to ocean acidification. In this hypothesis, proteins and membranes exposed to the external environment, such as epithelial tissues, may be susceptible to changes in external pH. Such biochemical systems could be adapted to a reduced pH environment by adjustment of weak bonds in an analogous fashion to biochemical adaptation to temperature. Whether such biochemical adaptation to OA exists remains to be discovered. © 2015. Published by The Company of Biologists Ltd.

  17. Advances in targeting strategies for nanoparticles in cancer imaging and therapy.

    PubMed

    Yhee, Ji Young; Lee, Sangmin; Kim, Kwangmeyung

    2014-11-21

    In the last decade, nanoparticles have offered great advances in diagnostic imaging and targeted drug delivery. In particular, nanoparticles have provided remarkable progress in cancer imaging and therapy based on materials science and biochemical engineering technology. Researchers constantly attempted to develop the nanoparticles which can deliver drugs more specifically to cancer cells, and these efforts brought the advances in the targeting strategy of nanoparticles. This minireview will discuss the progress in targeting strategies for nanoparticles focused on the recent innovative work for nanomedicine.

  18. Chemical evolution and the origin of life.

    PubMed

    Oro, J

    1983-01-01

    During the last three decades major advances have been made in our understanding of the formation of carbon compounds in the universe and of the occurence of processes of chemical evolution. 1) Carbon and other biogenic elements (C,H,N,O,S and P) are some of the most abundant in the universe. 2) The interstellar medium has been found to contain a diversity of molecules of these elements. 3) Some of these molecules have also been found in comets which are considered the most primordial bodies of the solar system. 4) The atmospheres of the outer planets and their satellites, for example, Titan, are actively involved in the formation of organic compounds which are the precursors of biochemical molecules. 5) Some of these biochemical molecules, such as amino acids, purines and pyrimidines, have been found in carbonaceous chondrites. 6) Laboratory experiments have shown that most of the monomers and oligomers necessary for life can be synthesized under hypothesized but plausible primitive Earth conditions from compounds found in the above cosmic bodies. 7) It appears that the primitive Earth had the necessary and sufficient conditions to allow the chemical synthesis of biomacromolecules and to permit the processes required for the emergence of life on our planet. 8) It is unlikely that the emergence of life occurred in any other body of the solar system, although the examination of the Jovian satellite Europa may provide important clues about the constraints of this evolutionary process. Some of the fundamental principles of chemical evolution are briefly discussed.

  19. Review: The effect of nutrition on timing of pubertal onset and subsequent fertility in the bull.

    PubMed

    Kenny, D A; Byrne, C J

    2018-06-01

    The advent of genomic selection has led to increased interest within the cattle breeding industry to market semen from young bulls as early as possible. However, both the quantity and quality of such semen is dictated by the age at which these animals reach puberty. Enhancing early life plane of nutrition of the bull stimulates a complex biochemical interplay involving metabolic and neuroendocrine signalling and culminating in enhanced testicular growth and development and earlier onset of sexual maturation. Recent evidence suggests that an enhanced plane of nutrition leads to an advancement of testicular development in bulls at 18 weeks of age. However, as of yet, much of the neuronal mechanisms regulating these developmental processes remain to be elucidated in the bull. While early life nutrition clearly affects the sexual maturation process in bulls, there is little evidence for latent effects on semen traits post-puberty. Equally the influence of prevailing nutritional status on the fertility of mature bulls is unclear though management practices that result in clinical or even subclinical metabolic disease can undoubtedly impact upon normal sexual function. Dietary supplements enriched with various polyunsaturated fatty acids or fortified with trace elements do not consistently affect reproductive function in the bull, certainly where animals are already adequately nourished. Further insight on how nutrition mediates the biochemical interaction between neuroendocrine and testicular processes will facilitate optimisation of nutritional regimens to optimise sexual maturation and subsequent semen production in bulls.

  20. Biotechnologies as a Context for Enhancing Junior High-School Students' Ability to Ask Meaningful Questions about Abstract Biological Processes.

    ERIC Educational Resources Information Center

    Olsher, G.; Dreyfus, A.

    1999-01-01

    Suggests a new approach to teaching about biochemical cellular processes by stimulating student interest in those biochemical processes that allowed for the outcomes of modern biotechnologies. Discusses the development of students' ability to ask meaningful questions about intra-cellular processes, and the resulting meaningful learning of relevant…

  1. Strategies for target identification of antimicrobial natural products.

    PubMed

    Farha, Maya A; Brown, Eric D

    2016-05-04

    Covering: 2000 to 2015Despite a pervasive decline in natural product research at many pharmaceutical companies over the last two decades, natural products have undeniably been a prolific and unsurpassed source for new lead antibacterial compounds. Due to their inherent complexity, natural extracts face several hurdles in high-throughout discovery programs, including target identification. Target identification and validation is a crucial process for advancing hits through the discovery pipeline, but has remained a major bottleneck. In the case of natural products, extremely low yields and limited compound supply further impede the process. Here, we review the wealth of target identification strategies that have been proposed and implemented for the characterization of novel antibacterials. Traditionally, these have included genomic and biochemical-based approaches, which, in recent years, have been improved with modern-day technology and better honed for natural product discovery. Further, we discuss the more recent innovative approaches for uncovering the target of new antibacterial natural products, which have resulted from modern advances in chemical biology tools. Finally, we present unique screening platforms implemented to streamline the process of target identification. The different innovative methods to respond to the challenge of characterizing the mode of action for antibacterial natural products have cumulatively built useful frameworks that may advocate a renovated interest in natural product drug discovery programs.

  2. Recent Progress in Advanced Nanobiological Materials for Energy and Environmental Applications

    PubMed Central

    Choi, Hyo-Jick; Montemagno, Carlo D.

    2013-01-01

    In this review, we briefly introduce our efforts to reconstruct cellular life processes by mimicking natural systems and the applications of these systems to energy and environmental problems. Functional units of in vitro cellular life processes are based on the fabrication of artificial organelles using protein-incorporated polymersomes and the creation of bioreactors. This concept of an artificial organelle originates from the first synthesis of poly(siloxane)-poly(alkyloxazoline) block copolymers three decades ago and the first demonstration of protein activity in the polymer membrane a decade ago. The increased value of biomimetic polymers results from many research efforts to find new applications such as functionally active membranes and a biochemical-producing polymersome. At the same time, foam research has advanced to the point that biomolecules can be efficiently produced in the aqueous channels of foam. Ongoing research includes replication of complex biological processes, such as an artificial Calvin cycle for application in biofuel and specialty chemical production, and carbon dioxide sequestration. We believe that the development of optimally designed biomimetic polymers and stable/biocompatible bioreactors would contribute to the realization of the benefits of biomimetic systems. Thus, this paper seeks to review previous research efforts, examine current knowledge/key technical parameters, and identify technical challenges ahead. PMID:28788424

  3. Landauer in the Age of Synthetic Biology: Energy Consumption and Information Processing in Biochemical Networks

    NASA Astrophysics Data System (ADS)

    Mehta, Pankaj; Lang, Alex H.; Schwab, David J.

    2016-03-01

    A central goal of synthetic biology is to design sophisticated synthetic cellular circuits that can perform complex computations and information processing tasks in response to specific inputs. The tremendous advances in our ability to understand and manipulate cellular information processing networks raises several fundamental physics questions: How do the molecular components of cellular circuits exploit energy consumption to improve information processing? Can one utilize ideas from thermodynamics to improve the design of synthetic cellular circuits and modules? Here, we summarize recent theoretical work addressing these questions. Energy consumption in cellular circuits serves five basic purposes: (1) increasing specificity, (2) manipulating dynamics, (3) reducing variability, (4) amplifying signal, and (5) erasing memory. We demonstrate these ideas using several simple examples and discuss the implications of these theoretical ideas for the emerging field of synthetic biology. We conclude by discussing how it may be possible to overcome these limitations using "post-translational" synthetic biology that exploits reversible protein modification.

  4. Biochemical Conversion: Using Enzymes, Microbes, and Catalysis to Make Fuels and Chemicals

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

    None

    2013-07-26

    This fact sheet describes the Bioenergy Technologies Office's biochemical conversion work and processes. BETO conducts collaborative research, development, and demonstration projects to improve several processing routes for the conversion of cellulosic biomass.

  5. Hydration in advanced cancer: can bioelectrical impedance analysis improve the evidence base? A systematic review of the literature.

    PubMed

    Nwosu, Amara Callistus; Mayland, Catriona R; Mason, Stephen R; Khodabukus, Andrew F; Varro, Andrea; Ellershaw, John E

    2013-09-01

    Decisions surrounding the administration of clinically assisted hydration to patients dying of cancer can be challenging because of the limited understanding of hydration in advanced cancer and a lack of evidence to guide health care professionals. Bioelectrical impedance analysis (BIA) has been used to assess hydration in various patient groupings, but evidence for its use in advanced cancer is limited. To critically appraise existing methods of hydration status assessment in advanced cancer and review the potential for BIA to assess hydration in advanced cancer. Searches were carried out in four electronic databases. A hand search of selected peer-reviewed journals and conference abstracts also was conducted. Studies reporting (de)hydration assessment (physical examination, biochemical measures, symptom assessment, and BIA) in patients with advanced cancer were included. The results highlight how clinical examination and biochemical tests are standard methods of assessing hydration, but limitations exist with these methods in advanced cancer. Furthermore, there is disagreement over the evidence for some commonly associated symptoms with dehydration in cancer. Although there are limitations with using BIA alone to assess hydration in advanced cancer, analysis of BIA raw measurements through the method of bioelectrical impedance vector analysis may have a role in this population. The benefits and burdens of providing clinically assisted hydration to patients dying of cancer are unclear. Bioelectrical impedance vector analysis shows promise as a hydration assessment tool but requires further study in advanced cancer. Innovative methodologies for research are required to add to the evidence base and ultimately improve the care for the dying. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  6. Turfgrass diagnostics and new, advanced technologies

    USDA-ARS?s Scientific Manuscript database

    Strategies for sustainable, integrated disease management start with reliable pathogen identification. Conventional identification methods such as disease symptomology, host association, morphology and biochemical tests are still key diagnostic indicators for many phytopathogens; however, nucleic ac...

  7. Metals and minerals as a biotechnology feedstock: engineering biomining microbiology for bioenergy applications.

    PubMed

    Banerjee, Indrani; Burrell, Brittany; Reed, Cara; West, Alan C; Banta, Scott

    2017-06-01

    Developing new feedstocks for the efficient production of biochemicals and biofuels will be a critical challenge as we diversify away from petrochemicals. One possible opportunity is the utilization of sulfide-based minerals in the Earth's crust. Non-photosynthetic chemolithoautotrophic bacteria are starting to be developed to produce biochemicals from CO 2 using energy obtained from the oxidation of inorganic feedstocks. Biomining of metals like gold and copper already exploit the native metabolism of these bacteria and these represent perhaps the largest-scale bioprocesses ever developed. The metabolic engineering of these bacteria could be a desirable alternative to classical heterotrophic bioproduction. In this review, we discuss biomining operations and the challenges and advances in the engineering of associated chemolithoautotrophic bacteria for biofuel production. The co-generation of biofuels integrated with mining operations is a largely unexplored opportunity that will require advances in fundamental microbiology and the development of new genetic tools and techniques for these organisms. Although this approach is presently in its infancy, the production of biochemicals using energy from non-petroleum mineral resources is an exciting new biotechnology opportunity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Hereditary rickets. How genetic alterations explain the biochemical and clinical phenotypes.

    PubMed

    Papadopoulou, Anna; Gole, Evaggelia; Nicolaidou, Polyxeni

    2013-12-01

    The reemergence of vitamin D deficiency in the industrialized countries resurrects the "threat" of nutritional rickets, especially among pediatric populations, a fact that may lead to underdiagnosis of hereditary rickets. Today, hereditary rickets may be subdivided into two main groups according to their biochemical profile: the one associated with defects in vitamin D synthesis and action and the second associated with abnormal phosphorus metabolism. The classification of the patients in a particular group of hereditary rickets is determinative of the treatment to follow. This review, through the recent advances on vitamin D and P metabolism, discusses the molecular and biochemical defects associated to each group of inherited rickets, as well as the clinical phenotypes and the recommended therapeutic approaches.

  9. New insights into human primordial germ cells and early embryonic development from single-cell analysis.

    PubMed

    Otte, Jörg; Wruck, Wasco; Adjaye, James

    2017-08-01

    Human preimplantation developmental studies are difficult to accomplish due to associated ethical and moral issues. Preimplantation cells are rare and exist only in transient cell states. From a single cell, it is very challenging to analyse the origination of the heterogeneity and complexity inherent to the human body. However, recent advances in single-cell technology and data analysis have provided new insights into the process of early human development and germ cell specification. In this Review, we examine the latest single-cell datasets of human preimplantation embryos and germ cell development, compare them to bulk cell analyses, and interpret their biological implications. © 2017 Federation of European Biochemical Societies.

  10. Poly (lactic acid)-based biomaterials for orthopaedic regenerative engineering.

    PubMed

    Narayanan, Ganesh; Vernekar, Varadraj N; Kuyinu, Emmanuel L; Laurencin, Cato T

    2016-12-15

    Regenerative engineering converges tissue engineering, advanced materials science, stem cell science, and developmental biology to regenerate complex tissues such as whole limbs. Regenerative engineering scaffolds provide mechanical support and nanoscale control over architecture, topography, and biochemical cues to influence cellular outcome. In this regard, poly (lactic acid) (PLA)-based biomaterials may be considered as a gold standard for many orthopaedic regenerative engineering applications because of their versatility in fabrication, biodegradability, and compatibility with biomolecules and cells. Here we discuss recent developments in PLA-based biomaterials with respect to processability and current applications in the clinical and research settings for bone, ligament, meniscus, and cartilage regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. ISS Biotechnology Facility - Overview of Analytical Tools for Cellular Biotechnology Investigations

    NASA Technical Reports Server (NTRS)

    Jeevarajan, A. S.; Towe, B. C.; Anderson, M. M.; Gonda, S. R.; Pellis, N. R.

    2001-01-01

    The ISS Biotechnology Facility (BTF) platform provides scientists with a unique opportunity to carry out diverse experiments in a microgravity environment for an extended period of time. Although considerable progress has been made in preserving cells on the ISS for long periods of time for later return to Earth, future biotechnology experiments would desirably monitor, process, and analyze cells in a timely way on-orbit. One aspect of our work has been directed towards developing biochemical sensors for pH, glucose, oxygen, and carbon dioxide for perfused bioreactor system developed at Johnson Space Center. Another aspect is the examination and identification of new and advanced commercial biotechnologies that may have applications to on-orbit experiments.

  12. A cross-omics toxicological evaluation of drinking water treated with different processes.

    PubMed

    Shi, Peng; Jia, Shuyu; Zhang, Xu-Xiang; Zhao, Fuzheng; Chen, Yajun; Zhou, Qing; Cheng, Shupei; Li, Ai-Min

    2014-04-30

    Cross-omics profiling and phenotypic analysis were conducted to comprehensively assess the toxicities of source of drinking water (SDW), effluent of conventional treatment (ECT) and effluent of advanced treatment (EAT) in a water treatment plant. SDW feeding increased body weight, and relative liver and kidney weights of mice. Hepatic histopathological damages and serum biochemical alterations were observed in the mice fed with SDW and ECT, but EAT feeding showed no obvious effects. Transcriptomic analysis demonstrated that exposure to water samples caused differential expression of hundreds of genes in livers. Cluster analysis of the differentially expressed genes which generated by both microarrays and digital gene expression showed similar grouping patterns. Proteomic and metabolomics analyses indicated that drinking SDW, ECT and EAT generated 59, 145 and 41 significantly altered proteins in livers and 8, 2 and 0 altered metabolites in serum, respectively. SDW was found to affect several metabolic pathways including metabolism of xenobiotics by cytochrome P450 and fatty acid metabolism. SDW and ECT might induce molecular toxicities to mice, but the advanced treatment process can reduce the potential health risk by effectively removing toxic chemicals in drinking water. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. "Chemical transformers" from nanoparticle ensembles operated with logic.

    PubMed

    Motornov, Mikhail; Zhou, Jian; Pita, Marcos; Gopishetty, Venkateshwarlu; Tokarev, Ihor; Katz, Evgeny; Minko, Sergiy

    2008-09-01

    The pH-responsive nanoparticles were coupled with information-processing enzyme-based systems to yield "smart" signal-responsive hybrid systems with built-in Boolean logic. The enzyme systems performed AND/OR logic operations, transducing biochemical input signals into reversible structural changes (signal-directed self-assembly) of the nanoparticle assemblies, thus resulting in the processing and amplification of the biochemical signals. The hybrid system mimics biological systems in effective processing of complex biochemical information, resulting in reversible changes of the self-assembled structures of the nanoparticles. The bioinspired approach to the nanostructured morphing materials could be used in future self-assembled molecular robotic systems.

  14. Investigation of thermochemical biorefinery sizing and environmental sustainability impacts for conventional supply system and distributed pre-processing supply system designs

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

    David J. Muth, Jr.; Matthew H. Langholtz; Eric C. D. Tan

    The 2011 US Billion-Ton Update estimates that by 2030 there will be enough agricultural and forest resources to sustainably provide at least one billion dry tons of biomass annually, enough to displace approximately 30% of the country's current petroleum consumption. A portion of these resources are inaccessible at current cost targets with conventional feedstock supply systems because of their remoteness or low yields. Reliable analyses and projections of US biofuels production depend on assumptions about the supply system and biorefinery capacity, which, in turn, depend upon economic value, feedstock logistics, and sustainability. A cross-functional team has examined combinations of advancesmore » in feedstock supply systems and biorefinery capacities with rigorous design information, improved crop yield and agronomic practices, and improved estimates of sustainable biomass availability. A previous report on biochemical refinery capacity noted that under advanced feedstock logistic supply systems that include depots and pre-processing operations there are cost advantages that support larger biorefineries up to 10 000 DMT/day facilities compared to the smaller 2000 DMT/day facilities. This report focuses on analyzing conventional versus advanced depot biomass supply systems for a thermochemical conversion and refinery sizing based on woody biomass. The results of this analysis demonstrate that the economies of scale enabled by advanced logistics offsets much of the added logistics costs from additional depot processing and transportation, resulting in a small overall increase to the minimum ethanol selling price compared to the conventional logistic supply system. While the overall costs do increase slightly for the advanced logistic supply systems, the ability to mitigate moisture and ash in the system will improve the storage and conversion processes. In addition, being able to draw on feedstocks from further distances will decrease the risk of biomass supply to the conversion facility.« less

  15. Post-translational modifications are key players of the Legionella pneumophila infection strategy

    PubMed Central

    Michard, Céline; Doublet, Patricia

    2015-01-01

    Post-translational modifications (PTMs) are widely used by eukaryotes to control the enzymatic activity, localization or stability of their proteins. Traditionally, it was believed that the broad biochemical diversity of the PTMs is restricted to eukaryotic cells, which exploit it in extensive networks to fine-tune various and complex cellular functions. During the last decade, the advanced detection methods of PTMs and functional studies of the host–pathogen relationships highlight that bacteria have also developed a large arsenal of PTMs, particularly to subvert host cell pathways to their benefit. Legionella pneumophila, the etiological agent of the severe pneumonia legionellosis, is the paradigm of highly adapted intravacuolar pathogens that have set up sophisticated biochemical strategies. Among them, L. pneumophila has evolved eukaryotic-like and rare/novel PTMs to hijack host cell processes. Here, we review recent progress about the diversity of PTMs catalyzed by Legionella: ubiquitination, prenylation, phosphorylation, glycosylation, methylation, AMPylation, and de-AMPylation, phosphocholination, and de-phosphocholination. We focus on the host cell pathways targeted by the bacteria catalyzed PTMs and we stress the importance of the PTMs in the Legionella infection strategy. Finally, we highlight that the discovery of these PTMs undoubtedly made significant breakthroughs on the molecular basis of Legionella pathogenesis but also lead the way in improving our knowledge of the eukaryotic PTMs and complex cellular processes that are associated to. PMID:25713573

  16. Optical tweezers and multiphoton microscopies integrated photonic tool for mechanical and biochemical cell processes studies

    NASA Astrophysics Data System (ADS)

    de Thomaz, A. A.; Faustino, W. M.; Fontes, A.; Fernandes, H. P.; Barjas-Castro, M. d. L.; Metze, K.; Giorgio, S.; Barbosa, L. C.; Cesar, C. L.

    2007-09-01

    The research in biomedical photonics is clearly evolving in the direction of the understanding of biological processes at the cell level. The spatial resolution to accomplish this task practically requires photonics tools. However, an integration of different photonic tools and a multimodal and functional approach will be necessary to access the mechanical and biochemical cell processes. This way we can observe mechanicaly triggered biochemical events or biochemicaly triggered mechanical events, or even observe simultaneously mechanical and biochemical events triggered by other means, e.g. electricaly. One great advantage of the photonic tools is its easiness for integration. Therefore, we developed such integrated tool by incorporating single and double Optical Tweezers with Confocal Single and Multiphoton Microscopies. This system can perform 2-photon excited fluorescence and Second Harmonic Generation microscopies together with optical manipulations. It also can acquire Fluorescence and SHG spectra of specific spots. Force, elasticity and viscosity measurements of stretched membranes can be followed by real time confocal microscopies. Also opticaly trapped living protozoas, such as leishmania amazonensis. Integration with CARS microscopy is under way. We will show several examples of the use of such integrated instrument and its potential to observe mechanical and biochemical processes at cell level.

  17. Functional optical coherence tomography: principles and progress

    NASA Astrophysics Data System (ADS)

    Kim, Jina; Brown, William; Maher, Jason R.; Levinson, Howard; Wax, Adam

    2015-05-01

    In the past decade, several functional extensions of optical coherence tomography (OCT) have emerged, and this review highlights key advances in instrumentation, theoretical analysis, signal processing and clinical application of these extensions. We review five principal extensions: Doppler OCT (DOCT), polarization-sensitive OCT (PS-OCT), optical coherence elastography (OCE), spectroscopic OCT (SOCT), and molecular imaging OCT. The former three have been further developed with studies in both ex vivo and in vivo human tissues. This review emphasizes the newer techniques of SOCT and molecular imaging OCT, which show excellent potential for clinical application but have yet to be well reviewed in the literature. SOCT elucidates tissue characteristics, such as oxygenation and carcinogenesis, by detecting wavelength-dependent absorption and scattering of light in tissues. While SOCT measures endogenous biochemical distributions, molecular imaging OCT detects exogenous molecular contrast agents. These newer advances in functional OCT broaden the potential clinical application of OCT by providing novel ways to understand tissue activity that cannot be accomplished by other current imaging methodologies.

  18. Recent advances and industrial viewpoint for biological treatment of wastewaters by oleaginous microorganisms.

    PubMed

    Huang, Chao; Luo, Mu-Tan; Chen, Xue-Fang; Xiong, Lian; Li, Xiao-Mei; Chen, Xin-De

    2017-05-01

    Recently, technology of using oleaginous microorganisms for biological treatment of wastewaters has become one hot topic in biochemical and environmental engineering for its advantages such as easy for operation in basic bioreactor, having potential to produce valuable bio-products, efficient wastewaters treatment in short period, etc. To promote its industrialization, this article provides some comprehensive analysis of this technology such as its advances, issues, and outlook especially from industrial viewpoint. In detail, the types of wastewaters can be treated and the kinds of oleaginous microorganisms used for biological treatment are introduced, the potential of industrial application and issues (relatively low COD removal, low lipid yield, cost of operation, and lack of scale up application) of this technology are presented, and some critical outlook mainly on co-culture method, combination with other treatments, process controlling and adjusting are discussed systematically. By this article, some important information to develop this technology can be obtained. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Functional Optical Coherence Tomography: Principles and Progress

    PubMed Central

    Kim, Jina; Brown, William; Maher, Jason R.; Levinson, Howard; Wax, Adam

    2015-01-01

    In the past decade, several functional extensions of optical coherence tomography (OCT) have emerged, and this review highlights key advances in instrumentation, theoretical analysis, signal processing and clinical application of these extensions. We review five principal extensions: Doppler OCT (DOCT), polarization-sensitive OCT (PS-OCT), optical coherence elastography (OCE), spectroscopic OCT (SOCT), and molecular imaging OCT. The former three have been further developed with studies in both ex vivo and in vivo human tissues. This review emphasizes the newer techniques of SOCT and molecular imaging OCT, which show excellent potential for clinical application but have yet to be well reviewed in the literature. SOCT elucidates tissue characteristics, such as oxygenation and carcinogenesis, by detecting wavelength-dependent absorption and scattering of light in tissues. While SOCT measures endogenous biochemical distributions, molecular imaging OCT detects exogenous molecular contrast agents. These newer advances in functional OCT broaden the potential clinical application of OCT by providing novel ways to understand tissue activity that cannot be accomplished by other current imaging methodologies. PMID:25951836

  20. Genomic distribution and possible functions of DNA hydroxymethylation in the brain.

    PubMed

    Wen, Lu; Tang, Fuchou

    2014-11-01

    DNA methylation (5-methylcytosine, 5mC) is involved in many cellular processes and emerges as an important epigenetic player in brain development and memory formation. The recent discovery that 5mC can be oxidized to 5-hydroxymethylcytosine (5hmC) by TET (Ten-Eleven-Translocation) proteins provides novel insights into the dynamic character of 5mC in the brain. The content of 5hmC is remarkably high in the brain, adding further complexity. In this review, we discuss how recent advances have improved our understanding of the possible biological roles of 5hmC and TET proteins in the brain. These advances attribute to various approaches, including the genome-wide approach to map 5hmC in different genomic contexts, the gene knockout/knockdown approach to elucidate the functions of TET proteins and 5hmC, and the biochemical approach to uncover potential 5hmC readers. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Biochemical transformation of coals

    DOEpatents

    Lin, Mow S.; Premuzic, Eugene T.

    1999-03-23

    A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed.

  2. Biochemical upgrading of oils

    DOEpatents

    Premuzic, Eugene T.; Lin, Mow S.

    1999-01-12

    A process for biochemical conversion of heavy crude oils is provided. The process includes contacting heavy crude oils with adapted biocatalysts. The resulting upgraded oil shows, a relative increase in saturated hydrocarbons, emulsions and oxygenates and a decrease in compounds containing in organic sulfur, organic nitrogen and trace metals. Adapted microorganisms which have been modified under challenged growth processes are also disclosed.

  3. Biochemical upgrading of oils

    DOEpatents

    Premuzic, E.T.; Lin, M.S.

    1999-01-12

    A process for biochemical conversion of heavy crude oils is provided. The process includes contacting heavy crude oils with adapted biocatalysts. The resulting upgraded oil shows, a relative increase in saturated hydrocarbons, emulsions and oxygenates and a decrease in compounds containing organic sulfur, organic nitrogen and trace metals. Adapted microorganisms which have been modified under challenged growth processes are also disclosed. 121 figs.

  4. 21 CFR 315.5 - Evaluation of effectiveness.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

  5. 21 CFR 601.34 - Evaluation of effectiveness.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

  6. 21 CFR 315.5 - Evaluation of effectiveness.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

  7. 21 CFR 315.5 - Evaluation of effectiveness.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

  8. 21 CFR 601.34 - Evaluation of effectiveness.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

  9. 21 CFR 601.34 - Evaluation of effectiveness.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

  10. 21 CFR 315.5 - Evaluation of effectiveness.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

  11. 21 CFR 601.34 - Evaluation of effectiveness.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

  12. 21 CFR 601.34 - Evaluation of effectiveness.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

  13. 21 CFR 315.5 - Evaluation of effectiveness.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

  14. Biochemical transformation of solid carbonaceous material

    DOEpatents

    Lin, Mow S.; Premuzic, Eugene T.

    2001-09-25

    A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed.

  15. Biochemical transformation of coals

    DOEpatents

    Lin, M.S.; Premuzic, E.T.

    1999-03-23

    A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed. 7 figs.

  16. The underlying pathway structure of biochemical reaction networks

    PubMed Central

    Schilling, Christophe H.; Palsson, Bernhard O.

    1998-01-01

    Bioinformatics is yielding extensive, and in some cases complete, genetic and biochemical information about individual cell types and cellular processes, providing the composition of living cells and the molecular structure of its components. These components together perform integrated cellular functions that now need to be analyzed. In particular, the functional definition of biochemical pathways and their role in the context of the whole cell is lacking. In this study, we show how the mass balance constraints that govern the function of biochemical reaction networks lead to the translation of this problem into the realm of linear algebra. The functional capabilities of biochemical reaction networks, and thus the choices that cells can make, are reflected in the null space of their stoichiometric matrix. The null space is spanned by a finite number of basis vectors. We present an algorithm for the synthesis of a set of basis vectors for spanning the null space of the stoichiometric matrix, in which these basis vectors represent the underlying biochemical pathways that are fundamental to the corresponding biochemical reaction network. In other words, all possible flux distributions achievable by a defined set of biochemical reactions are represented by a linear combination of these basis pathways. These basis pathways thus represent the underlying pathway structure of the defined biochemical reaction network. This development is significant from a fundamental and conceptual standpoint because it yields a holistic definition of biochemical pathways in contrast to definitions that have arisen from the historical development of our knowledge about biochemical processes. Additionally, this new conceptual framework will be important in defining, characterizing, and studying biochemical pathways from the rapidly growing information on cellular function. PMID:9539712

  17. Toward metabolic engineering in the context of system biology and synthetic biology: advances and prospects.

    PubMed

    Liu, Yanfeng; Shin, Hyun-dong; Li, Jianghua; Liu, Long

    2015-02-01

    Metabolic engineering facilitates the rational development of recombinant bacterial strains for metabolite overproduction. Building on enormous advances in system biology and synthetic biology, novel strategies have been established for multivariate optimization of metabolic networks in ensemble, spatial, and dynamic manners such as modular pathway engineering, compartmentalization metabolic engineering, and metabolic engineering guided by genome-scale metabolic models, in vitro reconstitution, and systems and synthetic biology. Herein, we summarize recent advances in novel metabolic engineering strategies. Combined with advancing kinetic models and synthetic biology tools, more efficient new strategies for improving cellular properties can be established and applied for industrially important biochemical production.

  18. Challenging Density Functional Theory Calculations with Hemes and Porphyrins.

    PubMed

    de Visser, Sam P; Stillman, Martin J

    2016-04-07

    In this paper we review recent advances in computational chemistry and specifically focus on the chemical description of heme proteins and synthetic porphyrins that act as both mimics of natural processes and technological uses. These are challenging biochemical systems involved in electron transfer as well as biocatalysis processes. In recent years computational tools have improved considerably and now can reproduce experimental spectroscopic and reactivity studies within a reasonable error margin (several kcal·mol(-1)). This paper gives recent examples from our groups, where we investigated heme and synthetic metal-porphyrin systems. The four case studies highlight how computational modelling can correctly reproduce experimental product distributions, predicted reactivity trends and guide interpretation of electronic structures of complex systems. The case studies focus on the calculations of a variety of spectroscopic features of porphyrins and show how computational modelling gives important insight that explains the experimental spectra and can lead to the design of porphyrins with tuned properties.

  19. Objective characterization of bruise evolution using photothermal depth profiling and Monte Carlo modeling

    NASA Astrophysics Data System (ADS)

    Vidovič, Luka; Milanič, Matija; Majaron, Boris

    2015-01-01

    Pulsed photothermal radiometry (PPTR) allows noninvasive determination of laser-induced temperature depth profiles in optically scattering layered structures. The obtained profiles provide information on spatial distribution of selected chromophores such as melanin and hemoglobin in human skin. We apply the described approach to study time evolution of incidental bruises (hematomas) in human subjects. By combining numerical simulations of laser energy deposition in bruised skin with objective fitting of the predicted and measured PPTR signals, we can quantitatively characterize the key processes involved in bruise evolution (i.e., hemoglobin mass diffusion and biochemical decomposition). Simultaneous analysis of PPTR signals obtained at various times post injury provides an insight into the variations of these parameters during the bruise healing process. The presented methodology and results advance our understanding of the bruise evolution and represent an important step toward development of an objective technique for age determination of traumatic bruises in forensic medicine.

  20. The Interaction of Global Biochemical Cycles

    NASA Technical Reports Server (NTRS)

    Moore, B., III; Dastoor, M. N.

    1984-01-01

    The global biosphere in an exceedingly complex system. To gain an understanding of its structure and dynamic features, it is necessary not only to increase the knowledge about the detailed processes but also to develop models of how global interactions take place. Attempts to analyze the detailed physical, chemical and biological processes in this context need to be guided by an advancement of understanding of the latter. It is necessary to develop a strategy of data gathering that severs both these purposes simultaneously. The following papers deal with critical aspects in the global cycles of carbon, nitrogen, phosphorus and sulfur in details as well as the cycle of water and the flow of energy in the Earth's environment. The objective is to set partly the foundation for the development of mathematical models that allow exploration of the coupled dynamics of the global cycles of carbon, nitrogen, phosphorus, sulfur, as well as energy and water flux.

  1. An Automated Peak Identification/Calibration Procedure for High-Dimensional Protein Measures From Mass Spectrometers.

    PubMed

    Yasui, Yutaka; McLerran, Dale; Adam, Bao-Ling; Winget, Marcy; Thornquist, Mark; Feng, Ziding

    2003-01-01

    Discovery of "signature" protein profiles that distinguish disease states (eg, malignant, benign, and normal) is a key step towards translating recent advancements in proteomic technologies into clinical utilities. Protein data generated from mass spectrometers are, however, large in size and have complex features due to complexities in both biological specimens and interfering biochemical/physical processes of the measurement procedure. Making sense out of such high-dimensional complex data is challenging and necessitates the use of a systematic data analytic strategy. We propose here a data processing strategy for two major issues in the analysis of such mass-spectrometry-generated proteomic data: (1) separation of protein "signals" from background "noise" in protein intensity measurements and (2) calibration of protein mass/charge measurements across samples. We illustrate the two issues and the utility of the proposed strategy using data from a prostate cancer biomarker discovery project as an example.

  2. A role for the geomagnetic field in cell regulation.

    PubMed

    Liboff, A R

    2010-08-01

    We advance the hypothesis that biological systems utilize the geomagnetic field (GMF) for functional purposes by means of ion cyclotron resonance-like (ICR) mechanisms. Numerous ICR-designed experiments have demonstrated that living things are sensitive, in varying degrees, to magnetic fields that are equivalent to both changes in the general magnetostatic intensity of the GMF, as well as its temporal perturbations. We propose the existence of ICR-like cell regulation processes, homologous to the way that biochemical messengers alter the net biological state through competing processes of enhancement and inhibition. In like manner, combinations of different resonance frequencies all coupled to the same local magnetic field provide a unique means for cell regulation. Recent work on ultraweak ICR magnetic fields by Zhadin and others fits into our proposed framework if one assumes that cellular systems generate time-varying electric fields of the order 100 mV/cm with bandwidths that include relevant ICR frequencies.

  3. Quo vadis plant hormone analysis?

    PubMed

    Tarkowská, Danuše; Novák, Ondřej; Floková, Kristýna; Tarkowski, Petr; Turečková, Veronika; Grúz, Jiří; Rolčík, Jakub; Strnad, Miroslav

    2014-07-01

    Plant hormones act as chemical messengers in the regulation of myriads of physiological processes that occur in plants. To date, nine groups of plant hormones have been identified and more will probably be discovered. Furthermore, members of each group may participate in the regulation of physiological responses in planta both alone and in concert with members of either the same group or other groups. The ideal way to study biochemical processes involving these signalling molecules is 'hormone profiling', i.e. quantification of not only the hormones themselves, but also their biosynthetic precursors and metabolites in plant tissues. However, this is highly challenging since trace amounts of all of these substances are present in highly complex plant matrices. Here, we review advances, current trends and future perspectives in the analysis of all currently known plant hormones and the associated problems of extracting them from plant tissues and separating them from the numerous potentially interfering compounds.

  4. The effect of high hydrostatic pressure on the physiological and biochemical properties of pepper (Capsicum annuum L.) seedlings

    NASA Astrophysics Data System (ADS)

    İşlek, Cemil; Murat Altuner, Ergin; Alpas, Hami

    2015-10-01

    High hydrostatic pressure is a non-thermal food processing technology, which also has several successful applications in different areas besides food processing. In this study, Capsicum annuum L. (pepper) seeds are subjected to 50, 100, 200 and 300 MPa pressure for 5 min at 25°C and the seedlings of HHP processed seeds are used to compare percentage of seed germination and biochemical properties such as chlorophyll a, b and a/b, proline content, total protein, carotenoid, malondialdehyde, glucose, fructose and phenolic compounds concentrations. As a result of the study, it was observed that there are remarkable changes in terms of biochemical properties especially for seedlings, whose seeds were pressurized at 200 and 300 MPa. More detailed studies are needed to put forward the mechanism behind the changes in biochemical properties.

  5. Dynamics of biochemical processes and redox conditions in geochemically linked landscapes of oligotrophic bogs

    NASA Astrophysics Data System (ADS)

    Inisheva, L. I.; Szajdak, L.; Sergeeva, M. A.

    2016-04-01

    The biological activity in oligotrophic peatlands at the margins of the Vasyugan Mire has been studied. It is shown found that differently directed biochemical processes manifest themselves in the entire peat profile down to the underlying mineral substrate. Their activity is highly variable. It is argued that the notion about active and inert layers in peat soils is only applicable for the description of their water regime. The degree of the biochemical activity is specified by the physical soil properties. As a result of the biochemical processes, a micromosaic aerobic-anaerobic medium is developed under the surface waterlogged layer of peat deposits. This layer contains the gas phase, including oxygen. It is concluded that the organic and mineral parts of peat bogs represent a single functional system of a genetic peat profile with a clear record of the history of its development.

  6. Acute and chronic hepatobiliary manifestations of sickle cell disease: A review

    PubMed Central

    Shah, Rushikesh; Taborda, Cesar; Chawla, Saurabh

    2017-01-01

    Sickle cell disease (SCD) is a common hemoglobinopathy which can affect multiple organ systems in the body. Within the digestive tract, the hepatobiliary system is most commonly affected in SCD. The manifestations range from benign hyperbilirubinemia to overt liver failure, with the spectrum of acute clinical presentations often referred to as “sickle cell hepatopathy”. This is an umbrella term referring to liver dysfunction and hyperbilirubinemia due to intrahepatic sickling process during SCD crisis leading to ischemia, sequestration and cholestasis. In this review, we detail the pathophysiology, clinical presentation and biochemical features of various acute and chronic hepatobiliary manifestations of SCD and present and evaluate existing evidence with regards to management of this disease process. We also discuss recent advances and controversies such as the role of liver transplantation in sickle cell hepatopathy and highlight important questions in this field which would require further research. Our aim with this review is to help increase the understanding, aid in early diagnosis and improve management of this important disease process. PMID:28868180

  7. Microstructure change in wood cell wall fracture from mechanical pretreatment and its influence on enzymatic hydrolysis

    Treesearch

    Jinxue Jiang; Jinwu Wang; Xiao Zhang; Michael Wolcott

    2017-01-01

    tMechanical pretreatment is an effective process for chemical or biochemical conversion of woodybiomass. The deconstruction features of the wood cell wall play an important role in its chemical or bio-chemical processing. In this work, we evaluated the wood cell wall fracture in the early stage of mechanicalpretreatment process conducted with various initial moisture...

  8. Antonella Amore | NREL

    Science.gov Websites

    Pleurotus ostreatus," Biotechnol. Appl. Biochem. (2014) "Enzymes for Food and Beverage Industries : Current Situation, Challenges and Perspectives" in Advances in Food Biotechnology (2013) " : Enzymatic and Microbial Tools for Bioethanol Production (2013) "Chemico-physical factors affecting food

  9. Removal efficiency and toxicity reduction of 4-chlorophenol with physical, chemical and biochemical methods.

    PubMed

    Gómez, M; Murcia, M D; Dams, R; Christofi, N; Gómez, E; Gómez, J L

    2012-01-01

    Chlorophenols are well-known priority pollutants and many different treatments have been assessed to facilitate their removal from industrial wastewater. However, an absolute and optimum solution still has to be practically implemented in an industrial setting. In this work, a series ofphysical, chemical and biochemical treatments have been systematically tested for the removal of 4-chlorophenol, and their results have been compared in order to determine the most effective treatment based on removal efficiency and residual by-product formation. Chemical treatments based on advanced oxidation processes (AOP) produced the best results on rate and extent of pollutant removal. The non-chemical technologies showed advantages in terms of complete (in the case of adsorption) or easy (enzymatic treatments) removal of toxic treatment by-products. The AOP methods led to the production of different photoproducts depending on the chosen treatment. Toxic products remained in most cases following treatment, though the toxicity level is significantly reduced with combination treatments. Among the treatments, a photochemical method combining UV, produced with a KrCl excilamp, and hydrogen peroxide achieved total removal of chlorophenol and all by-products and is considered the best treatment for chlorophenol removal.

  10. Foundations of a query and simulation system for the modeling of biochemical and biological processes.

    PubMed

    Antoniotti, M; Park, F; Policriti, A; Ugel, N; Mishra, B

    2003-01-01

    The analysis of large amounts of data, produced as (numerical) traces of in vivo, in vitro and in silico experiments, has become a central activity for many biologists and biochemists. Recent advances in the mathematical modeling and computation of biochemical systems have moreover increased the prominence of in silico experiments; such experiments typically involve the simulation of sets of Differential Algebraic Equations (DAE), e.g., Generalized Mass Action systems (GMA) and S-systems. In this paper we reason about the necessary theoretical and pragmatic foundations for a query and simulation system capable of analyzing large amounts of such trace data. To this end, we propose to combine in a novel way several well-known tools from numerical analysis (approximation theory), temporal logic and verification, and visualization. The result is a preliminary prototype system: simpathica/xssys. When dealing with simulation data simpathica/xssys exploits the special structure of the underlying DAE, and reduces the search space in an efficient way so as to facilitate any queries about the traces. The proposed system is designed to give the user possibility to systematically analyze and simultaneously query different possible timed evolutions of the modeled system.

  11. Control of microenvironmental cues with a smart biomaterial composite promotes endothelial progenitor cell angiogenesis.

    PubMed

    Aguirre, Aitor; González, Arlyng; Navarro, Melba; Castaño, Óscar; Planell, Josep A; Engel, Elisabeth

    2012-07-24

    Smart biomaterials play a key role when aiming at successful tissue repair by means of regenerative medicine approaches, and are expected to contain chemical as well as mechanical cues that will guide the regenerative process. Recent advances in the understanding of stem cell biology and mechanosensing have shed new light onto the importance of the local microenvironment in determining cell fate. Herein we report the biological properties of a bioactive, biodegradable calcium phosphate glass/polylactic acid composite biomaterial that promotes bone marrow-derived endothelial progenitor cell (EPC) mobilisation, differentiation and angiogenesis through the creation of a controlled bone healing-like microenvironment. The angiogenic response is triggered by biochemical and mechanical cues provided by the composite, which activate two synergistic cell signalling pathways: a biochemical one mediated by the calcium-sensing receptor and a mechanosensitive one regulated by non-muscle myosin II contraction. Together, these signals promote a synergistic response by activating EPCs-mediated VEGF and VEGFR-2 synthesis, which in turn promote progenitor cell homing, differentiation and tubulogenesis. These findings highlight the importance of controlling microenvironmental cues for stem/progenitor cell tissue engineering and offer exciting new therapeutical opportunities for biomaterial-based vascularisation approaches and clinical applications.

  12. A Compendium of Volatile Organic Compounds (VOCs) Released By Human Cell Lines

    PubMed Central

    Filipiak, Wojciech; Mochalski, Pawel; Filipiak, Anna; Ager, Clemens; Cumeras, Raquel; Davis, Cristina E.; Agapiou, Agapios; Unterkofler, Karl; Troppmair, Jakob

    2016-01-01

    Volatile organic compounds (VOCs) offer unique insights into ongoing biochemical processes in healthy and diseased humans. Yet, their diagnostic use is hampered by the limited understanding of their biochemical or cellular origin and their frequently unclear link to the underlying diseases. Major advancements are expected from the analyses of human primary cells, cell lines and cultures of microorganisms. In this review, a database of 125 reliably identified VOCs previously reported for human healthy and diseased cells was assembled and their potential origin is discussed. The majority of them have also been observed in studies with other human matrices (breath, urine, saliva, feces, blood, skin emanations). Moreover, continuing improvements of qualitative and quantitative analyses, based on the recommendations of the ISO-11843 guidelines, are suggested for the necessary standardization of analytical procedures and better comparability of results. The data provided contribute to arriving at a more complete human volatilome and suggest potential volatile biomarkers for future validation. Dedication: This review is dedicated to the memory of Prof. Dr. Anton Amann, who sadly passed away on January 6, 2015. He was motivator and motor for the field of breath research. PMID:27160536

  13. (Bio)Chemical Tailoring of Biogenic 3-D Nanopatterned Templates with Energy-Relevant Functionalities

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

    Sandhage, Kenneth H; Kroger, Nils

    2014-09-08

    The overall aim of this research has been to obtain fundamental understanding of (bio)chemical methodologies that will enable utilization of the unique 3-D nanopatterned architectures naturally produced by diatoms for the syntheses of advanced functional materials attractive for applications in energy harvesting/conversion and storage. This research has been conducted in three thrusts: Thrust 1 (In vivo immobilization of proteins in diatom biosilica) is directed towards elucidating the fundamental mechanism(s) underlying the cellular processes of in vivo immobilization of proteins in diatom silica. Thrust 2 (Shape-preserving reactive conversion of diatom biosilica into porous, high-surface area inorganic replicas) is aimed at understandingmore » the fundamental mechanisms of shape preservation and nanostructural evolution associated with the reactive conversion and/or coating-based conversion of diatom biosilica templates into porous inorganic replicas. Thrust 3 (Immobilization of energy-relevant enzymes in diatom biosilica and onto diatom biosilica-derived inorganic replicas) involves use of the results from both Thrust 1 and 2 to develop strategies for in vivo and in vitro immobilization of enzymes in/on diatom biosilica and diatom biosilica-derived inorganic replicas, respectively. This Final Report describes progress achieved in all 3 of these thrusts.« less

  14. Biosensors and bioelectronics on smartphone for portable biochemical detection.

    PubMed

    Zhang, Diming; Liu, Qingjun

    2016-01-15

    Smartphone has been widely integrated with sensors, such as test strips, sensor chips, and hand-held detectors, for biochemical detections due to its portability and ubiquitous availability. Utilizing built-in function modules, smartphone is often employed as controller, analyzer, and displayer for rapid, real-time, and point-of-care monitoring, which can significantly simplify design and reduce cost of the detecting systems. This paper presents a review of biosensors and bioelectronics on smartphone for portable biochemical detections. The biosensors and bioelectronics based on smartphone can mainly be classified into biosensors using optics, surface plasmon resonance, electrochemistry, and near-field communication. The developments of these biosensors and bioelectronics on smartphone are reviewed along with typical biochemical detecting cases. Sensor strategies, detector attachments, and coupling methods are highlighted to show designs of the compact, lightweight, and low-cost sensor systems. The performances and advantages of these designs are introduced with their applications in healthcare diagnosis, environment monitoring, and food evaluation. With advances in micro-manufacture, sensor technology, and miniaturized electronics, biosensor and bioelectronic devices on smartphone can be used to perform biochemical detections as common and convenient as electronic tag readout in foreseeable future. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Cannabidiol--recent advances.

    PubMed

    Mechoulam, Raphael; Peters, Maximilian; Murillo-Rodriguez, Eric; Hanus, Lumír O

    2007-08-01

    The aim of this review is to present some of the recent publications on cannabidiol (CBD; 2), a major non-psychoactive constituent of Cannabis, and to give a general overview. Special emphasis is laid on biochemical and pharmacological advances, and on novel mechanisms recently put forward, to shed light on some of the pharmacological effects that can possibly be rationalized through these mechanisms. The plethora of positive pharmacological effects observed with CBD make this compound a highly attractive therapeutic entity.

  16. Matt Wecker | NREL

    Science.gov Websites

    acetaldehyde from bacteria. The idea was to short-sheet the ethanol fermentation pathway to produce ; Biochem. (1995) "Fermentation strategies: Acetaldehyde or ethanol?," Process Biochem. (1987

  17. In vitro studies of actin filament and network dynamics

    PubMed Central

    Mullins, R Dyche; Hansen, Scott D

    2013-01-01

    Now that many genomes have been sequenced, a central concern of cell biology is to understand how the proteins they encode work together to create living matter. In vitro studies form an essential part of this program because understanding cellular functions of biological molecules often requires isolating them and reconstituting their activities. In particular, many elements of the actin cytoskeleton were first discovered by biochemical methods and their cellular functions deduced from in vitro experiments. We highlight recent advances that have come from in vitro studies, beginning with studies of actin filaments, and ending with multi-component reconstitutions of complex actin-based processes, including force-generation and cell spreading. We describe both scientific results and the technical innovations that made them possible. PMID:23267766

  18. Using cell deformation and motion to predict forces and collective behavior in morphogenesis.

    PubMed

    Merkel, Matthias; Manning, M Lisa

    2017-07-01

    In multi-cellular organisms, morphogenesis translates processes at the cellular scale into tissue deformation at the scale of organs and organisms. To understand how biochemical signaling regulates tissue form and function, we must understand the mechanical forces that shape cells and tissues. Recent progress in developing mechanical models for tissues has led to quantitative predictions for how cell shape changes and polarized cell motility generate forces and collective behavior on the tissue scale. In particular, much insight has been gained by thinking about biological tissues as physical materials composed of cells. Here we review these advances and discuss how they might help shape future experiments in developmental biology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. A multicellular view of cytokinesis in epithelial tissue.

    PubMed

    Herszterg, Sophie; Pinheiro, Diana; Bellaïche, Yohanns

    2014-05-01

    The study of cytokinesis in single-cell systems provided a wealth of knowledge on the molecular and biophysical mechanisms controlling daughter cell separation. In this review, we outline recent advances in the understanding of cytokinesis in epithelial tissues. These findings provide evidence for how the cytokinetic machinery adapts to a multicellular context and how the cytokinetic machinery is itself exploited by the tissue for the preservation of tissue function and architecture during proliferation. We propose that cytokinesis in epithelia should be viewed as a multicellular process, whereby the biochemical and mechanical interactions between the dividing cell and its neighbors are essential for successful daughter cell separation while defining epithelial tissue organization and preserving tissue integrity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Carotenoids from microalgae: A review of recent developments.

    PubMed

    Gong, Mengyue; Bassi, Amarjeet

    2016-12-01

    Carotenoids have been receiving increasing attention due to their potential health benefits. Microalgae are recognized as a natural source of carotenoids and other beneficial byproducts. However, the production of micro-algal carotenoids is not yet sufficiently cost-effective to compete with traditional chemical synthetic methods and other technologies such as extraction from plant based sources. This review presents the recent biotechnological developments in microalgal carotenoid production. The current technologies involved in their bioprocessing including cultivation, harvesting, extraction, and purification are discussed with a specific focus on downstream processing. The recent advances in chemical and biochemical synthesis of carotenoids are also reviewed for a better understanding of suitable and economically feasible biotechnological strategies. Some possible future directions are also proposed. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Harnessing Preclinical Molecular Imaging to Inform Advances in Personalized Cancer Medicine.

    PubMed

    Clark, Peter M; Ebiana, Victoria A; Gosa, Laura; Cloughesy, Timothy F; Nathanson, David A

    2017-05-01

    Comprehensive molecular analysis of individual tumors provides great potential for personalized cancer therapy. However, the presence of a particular genetic alteration is often insufficient to predict therapeutic efficacy. Drugs with distinct mechanisms of action can affect the biology of tumors in specific and unique ways. Therefore, assays that can measure drug-induced perturbations of defined functional tumor properties can be highly complementary to genomic analysis. PET provides the capacity to noninvasively measure the dynamics of various tumor biologic processes in vivo. Here, we review the underlying biochemical and biologic basis for a variety of PET tracers and how they may be used to better optimize cancer therapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  2. Positron emission tomography

    NASA Astrophysics Data System (ADS)

    Yamamoto, Y. Lucas; Thompson, Christopher J.; Diksic, Mirko; Meyer, Ernest; Feindel, William H.

    One of the most exciting new technologies introduced in the last 10 yr is positron emission tomography (PET). PET provides quantitative, three-dimensional images for the study of specific biochemical and physiological processes in the human body. This approach is analogous to quantitative in-vivo autoradiography but has the added advantage of permitting non-invasive in vivo studies. PET scanning requires a small cyclotron to produce short-lived positron emitting isotopes such as oxygen-15, carbon-11, nitrogen-13 and fluorine-18. Proper radiochemical facilities and advanced computer equipment are also needed. Most important, PET requires a multidisciplinary scientific team of physicists, radiochemists, mathematicians, biochemists and physicians. This review analyzes the most recent trends in the imaging technology, radiochemistry, methodology and clinical applications of positron emission tomography.

  3. Chemical evolution and the origin of life

    NASA Technical Reports Server (NTRS)

    Oro, J.

    1983-01-01

    A review is presented of recent advances made in the understanding of the formation of carbon compounds in the universe and the occurrence of processes of chemical evolution. Topics discussed include the principle of evolutionary continuity, evolution as a fundamental principle of the physical universe, the nuclear synthesis of biogenic elements, organic cosmochemistry and interstellar molecules, the solar nebula and the solar system in chemical evolution, the giant planets and Titan in chemical evolution, and comets and their interaction with the earth. Also examined are carbonaceous chondrites, environment of the primitive earth, energy sources available on the primitive earth, the synthesis of biochemical monomers and oligomers, the abiotic transcription of nucleotides, unified prebiotic and enzymatic mechanisms, phospholipids and membranes, and protobiological evolution.

  4. How did life survive Earth's great oxygenation?

    PubMed

    Fischer, Woodward W; Hemp, James; Valentine, Joan Selverstone

    2016-04-01

    Life on Earth originated and evolved in anoxic environments. Around 2.4 billion-years-ago, ancestors of Cyanobacteria invented oxygenic photosynthesis, producing substantial amounts of O2 as a byproduct of phototrophic water oxidation. The sudden appearance of O2 would have led to significant oxidative stress due to incompatibilities with core cellular biochemical processes. Here we examine this problem through the lens of Cyanobacteria-the first taxa to observe significant fluxes of intracellular dioxygen. These early oxygenic organisms likely adapted to the oxidative stress by co-opting preexisting systems (exaptation) with fortuitous antioxidant properties. Over time more advanced antioxidant systems evolved, allowing Cyanobacteria to adapt to an aerobic lifestyle and become the most important environmental engineers in Earth history. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Biochemical functionalization of peptide nanotubes with phage displayed peptides

    NASA Astrophysics Data System (ADS)

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering.

  6. Current Advances in the Biochemical and Physiological Aspects of the Treatment of Type 2 Diabetes Mellitus with Thiazolidinediones.

    PubMed

    Alemán-González-Duhart, D; Tamay-Cach, F; Álvarez-Almazán, S; Mendieta-Wejebe, J E

    2016-01-01

    The present review summarizes the current advances in the biochemical and physiological aspects in the treatment of type 2 diabetes mellitus (DM2) with thiazolidinediones (TZDs). DM2 is a metabolic disorder characterized by hyperglycemia, triggering the abnormal activation of physiological pathways such as glucose autooxidation, polyol's pathway, formation of advance glycation end (AGE) products, and glycolysis, leading to the overproduction of reactive oxygen species (ROS) and proinflammatory cytokines, which are responsible for the micro- and macrovascular complications of the disease. The treatment of DM2 has been directed toward the reduction of hyperglycemia using different drugs such as insulin sensitizers, as the case of TZDs, which are able to lower blood glucose levels and circulating triglycerides by binding to the nuclear peroxisome proliferator-activated receptor gamma (PPARγ) as full agonists. When TZDs interact with PPARγ, the receptor regulates the transcription of different genes involved in glucose homeostasis, insulin resistance, and adipogenesis. However, TZDs exhibit some adverse effects such as fluid retention, weight gain, hepatotoxicity, plasma-volume expansion, hemodilution, edema, bone fractures, and congestive heart failure, which limits their use in DM2 patients.

  7. Advanced tools for the analysis of protein phosphorylation in yeast mitochondria.

    PubMed

    Walter, Corvin; Gonczarowska-Jorge, Humberto; Sickmann, Albert; Zahedi, René P; Meisinger, Chris; Schmidt, Oliver

    2018-05-24

    The biochemical analysis of protein phosphorylation in mitochondria lags behind that of cytosolic signaling events. One reason is the poor stability of many phosphorylation sites during common isolation procedures for mitochondria. We present here an optimized, fast protocol for the purification of yeast mitochondria that greatly increases recovery of phosphorylated mitochondrial proteins. Moreover, we describe improved protocols for the biochemical analysis of mitochondrial protein phosphorylation by Zn 2+ -Phos-tag electrophoresis under both denaturing and - for the first time - native conditions, and demonstrate that they outperform previously applied methods. Copyright © 2018. Published by Elsevier Inc.

  8. Parallel medicinal chemistry approaches to selective HDAC1/HDAC2 inhibitor (SHI-1:2) optimization.

    PubMed

    Kattar, Solomon D; Surdi, Laura M; Zabierek, Anna; Methot, Joey L; Middleton, Richard E; Hughes, Bethany; Szewczak, Alexander A; Dahlberg, William K; Kral, Astrid M; Ozerova, Nicole; Fleming, Judith C; Wang, Hongmei; Secrist, Paul; Harsch, Andreas; Hamill, Julie E; Cruz, Jonathan C; Kenific, Candia M; Chenard, Melissa; Miller, Thomas A; Berk, Scott C; Tempest, Paul

    2009-02-15

    The successful application of both solid and solution phase library synthesis, combined with tight integration into the medicinal chemistry effort, resulted in the efficient optimization of a novel structural series of selective HDAC1/HDAC2 inhibitors by the MRL-Boston Parallel Medicinal Chemistry group. An initial lead from a small parallel library was found to be potent and selective in biochemical assays. Advanced compounds were the culmination of iterative library design and possess excellent biochemical and cellular potency, as well as acceptable PK and efficacy in animal models.

  9. Bioluminescence in the Ocean: Origins of Biological, Chemical, and Ecological Diversity

    NASA Astrophysics Data System (ADS)

    Widder, E. A.

    2010-05-01

    From bacteria to fish, a remarkable variety of marine life depends on bioluminescence (the chemical generation of light) for finding food, attracting mates, and evading predators. Disparate biochemical systems and diverse phylogenetic distribution patterns of light-emitting organisms highlight the ecological benefits of bioluminescence, with biochemical and genetic analyses providing new insights into the mechanisms of its evolution. The origins and functions of some bioluminescent systems, however, remain obscure. Here, I review recent advances in understanding bioluminescence in the ocean and highlight future research efforts that will unite molecular details with ecological and evolutionary relationships.

  10. Maximizing the Biochemical Resolving Power of Fluorescence Microscopy

    PubMed Central

    Esposito, Alessandro; Popleteeva, Marina; Venkitaraman, Ashok R.

    2013-01-01

    Most recent advances in fluorescence microscopy have focused on achieving spatial resolutions below the diffraction limit. However, the inherent capability of fluorescence microscopy to non-invasively resolve different biochemical or physical environments in biological samples has not yet been formally described, because an adequate and general theoretical framework is lacking. Here, we develop a mathematical characterization of the biochemical resolution in fluorescence detection with Fisher information analysis. To improve the precision and the resolution of quantitative imaging methods, we demonstrate strategies for the optimization of fluorescence lifetime, fluorescence anisotropy and hyperspectral detection, as well as different multi-dimensional techniques. We describe optimized imaging protocols, provide optimization algorithms and describe precision and resolving power in biochemical imaging thanks to the analysis of the general properties of Fisher information in fluorescence detection. These strategies enable the optimal use of the information content available within the limited photon-budget typically available in fluorescence microscopy. This theoretical foundation leads to a generalized strategy for the optimization of multi-dimensional optical detection, and demonstrates how the parallel detection of all properties of fluorescence can maximize the biochemical resolving power of fluorescence microscopy, an approach we term Hyper Dimensional Imaging Microscopy (HDIM). Our work provides a theoretical framework for the description of the biochemical resolution in fluorescence microscopy, irrespective of spatial resolution, and for the development of a new class of microscopes that exploit multi-parametric detection systems. PMID:24204821

  11. Digital photography provides a fast, reliable, and noninvasive method to estimate anthocyanin pigment concentration in reproductive and vegetative plant tissues.

    PubMed

    Del Valle, José C; Gallardo-López, Antonio; Buide, Mª Luisa; Whittall, Justen B; Narbona, Eduardo

    2018-03-01

    Anthocyanin pigments have become a model trait for evolutionary ecology as they often provide adaptive benefits for plants. Anthocyanins have been traditionally quantified biochemically or more recently using spectral reflectance. However, both methods require destructive sampling and can be labor intensive and challenging with small samples. Recent advances in digital photography and image processing make it the method of choice for measuring color in the wild. Here, we use digital images as a quick, noninvasive method to estimate relative anthocyanin concentrations in species exhibiting color variation. Using a consumer-level digital camera and a free image processing toolbox, we extracted RGB values from digital images to generate color indices. We tested petals, stems, pedicels, and calyces of six species, which contain different types of anthocyanin pigments and exhibit different pigmentation patterns. Color indices were assessed by their correlation to biochemically determined anthocyanin concentrations. For comparison, we also calculated color indices from spectral reflectance and tested the correlation with anthocyanin concentration. Indices perform differently depending on the nature of the color variation. For both digital images and spectral reflectance, the most accurate estimates of anthocyanin concentration emerge from anthocyanin content-chroma ratio, anthocyanin content-chroma basic, and strength of green indices. Color indices derived from both digital images and spectral reflectance strongly correlate with biochemically determined anthocyanin concentration; however, the estimates from digital images performed better than spectral reflectance in terms of r 2 and normalized root-mean-square error. This was particularly noticeable in a species with striped petals, but in the case of striped calyces, both methods showed a comparable relationship with anthocyanin concentration. Using digital images brings new opportunities to accurately quantify the anthocyanin concentrations in both floral and vegetative tissues. This method is efficient, completely noninvasive, applicable to both uniform and patterned color, and works with samples of any size.

  12. Investigation of thermochemical biorefinery sizing and environmental sustainability impacts for conventional supply system and distributed preprocessing supply system designs

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

    Muth, jr., David J.; Langholtz, Matthew H.; Tan, Eric

    2014-03-31

    The 2011 US Billion-Ton Update estimates that by 2030 there will be enough agricultural and forest resources to sustainably provide at least one billion dry tons of biomass annually, enough to displace approximately 30% of the country's current petroleum consumption. A portion of these resources are inaccessible at current cost targets with conventional feedstock supply systems because of their remoteness or low yields. Reliable analyses and projections of US biofuels production depend on assumptions about the supply system and biorefinery capacity, which, in turn, depend upon economic value, feedstock logistics, and sustainability. A cross-functional team has examined combinations of advancesmore » in feedstock supply systems and biorefinery capacities with rigorous design information, improved crop yield and agronomic practices, and improved estimates of sustainable biomass availability. A previous report on biochemical refinery capacity noted that under advanced feedstock logistic supply systems that include depots and pre-processing operations there are cost advantages that support larger biorefineries up to 10 000 DMT/day facilities compared to the smaller 2000 DMT/day facilities. This report focuses on analyzing conventional versus advanced depot biomass supply systems for a thermochemical conversion and refinery sizing based on woody biomass. The results of this analysis demonstrate that the economies of scale enabled by advanced logistics offsets much of the added logistics costs from additional depot processing and transportation, resulting in a small overall increase to the minimum ethanol selling price compared to the conventional logistic supply system. While the overall costs do increase slightly for the advanced logistic supply systems, the ability to mitigate moisture and ash in the system will improve the storage and conversion processes. In addition, being able to draw on feedstocks from further distances will decrease the risk of biomass supply to the conversion facility.« less

  13. Amino acids production focusing on fermentation technologies - A review.

    PubMed

    D'Este, Martina; Alvarado-Morales, Merlin; Angelidaki, Irini

    Amino acids are attractive and promising biochemicals with market capacity requirements constantly increasing. Their applicability ranges from animal feed additives, flavour enhancers and ingredients in cosmetic to specialty nutrients in pharmaceutical and medical fields. This review gives an overview of the processes applied for amino acids production and points out the main advantages and disadvantages of each. Due to the advances made in the genetic engineering techniques, the biotechnological processes, and in particular the fermentation with the aid of strains such as Corynebacterium glutamicum or Escherichia coli, play a significant role in the industrial production of amino acids. Despite the numerous advantages of the fermentative amino acids production, the process still needs significant improvements leading to increased productivity and reduction of the production costs. Although the production processes of amino acids have been extensively investigated in previous studies, a comprehensive overview of the developments in bioprocess technology has not been reported yet. This review states the importance of the fermentation process for industrial amino acids production, underlining the strengths and the weaknesses of the process. Moreover, the potential of innovative approaches utilizing macro and microalgae or bacteria are presented. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Peptide-nanocellulose sensor for human neutrophil elastase detection

    USDA-ARS?s Scientific Manuscript database

    Advances in biosensor technology promise to revolutionize healthcare and diagnosis with noninvasive methods. This is especially the case in the area of sensors for wound healing, where approaches for biochemical and cellular markers are emerging. Nanomaterials with high surface area and biocompatibl...

  15. Stochastic hybrid systems for studying biochemical processes.

    PubMed

    Singh, Abhyudai; Hespanha, João P

    2010-11-13

    Many protein and mRNA species occur at low molecular counts within cells, and hence are subject to large stochastic fluctuations in copy numbers over time. Development of computationally tractable frameworks for modelling stochastic fluctuations in population counts is essential to understand how noise at the cellular level affects biological function and phenotype. We show that stochastic hybrid systems (SHSs) provide a convenient framework for modelling the time evolution of population counts of different chemical species involved in a set of biochemical reactions. We illustrate recently developed techniques that allow fast computations of the statistical moments of the population count, without having to run computationally expensive Monte Carlo simulations of the biochemical reactions. Finally, we review different examples from the literature that illustrate the benefits of using SHSs for modelling biochemical processes.

  16. Pressure driven digital logic in PDMS based microfluidic devices fabricated by multilayer soft lithography.

    PubMed

    Devaraju, Naga Sai Gopi K; Unger, Marc A

    2012-11-21

    Advances in microfluidics now allow an unprecedented level of parallelization and integration of biochemical reactions. However, one challenge still faced by the field has been the complexity and cost of the control hardware: one external pressure signal has been required for each independently actuated set of valves on chip. Using a simple post-modification to the multilayer soft lithography fabrication process, we present a new implementation of digital fluidic logic fully analogous to electronic logic with significant performance advances over the previous implementations. We demonstrate a novel normally closed static gain valve capable of modulating pressure signals in a fashion analogous to an electronic transistor. We utilize these valves to build complex fluidic logic circuits capable of arbitrary control of flows by processing binary input signals (pressure (1) and atmosphere (0)). We demonstrate logic gates and devices including NOT, NAND and NOR gates, bi-stable flip-flops, gated flip-flops (latches), oscillators, self-driven peristaltic pumps, delay flip-flops, and a 12-bit shift register built using static gain valves. This fluidic logic shows cascade-ability, feedback, programmability, bi-stability, and autonomous control capability. This implementation of fluidic logic yields significantly smaller devices, higher clock rates, simple designs, easy fabrication, and integration into MSL microfluidics.

  17. Beyond histones - the expanding roles of protein lysine methylation.

    PubMed

    Wu, Zhouran; Connolly, Justin; Biggar, Kyle K

    2017-09-01

    A robust signaling network is essential for cell survival. At the molecular level, this is often mediated by as many as 200 different types of post-translational modifications (PTMs) that are made to proteins. These include well-documented examples such as phosphorylation, ubiquitination, acetylation and methylation. Of these modifications, non-histone protein lysine methylation has only recently emerged as a prevalent modification occurring on numerous proteins, thus extending its role well beyond the histone code. To date, this modification has been found to regulate protein activity, protein-protein interactions and interplay with other PTMs. As a result, lysine methylation is now known to be a coordinator of protein function and is a key driver in several cellular signaling events. Recent advances in mass spectrometry have also allowed the characterization of a growing number of lysine methylation events on an increasing number of proteins. As a result, we are now beginning to recognize lysine methylation as a dynamic event that is involved in a number of biological processes, including DNA damage repair, cell growth, metabolism and signal transduction among others. In light of current research advances, the stage is now set to study the extent of lysine methylation that exists within the entire proteome, its dynamics, and its association with physiological and pathological processes. © 2017 Federation of European Biochemical Societies.

  18. Training Signaling Pathway Maps to Biochemical Data with Constrained Fuzzy Logic: Quantitative Analysis of Liver Cell Responses to Inflammatory Stimuli

    PubMed Central

    Morris, Melody K.; Saez-Rodriguez, Julio; Clarke, David C.; Sorger, Peter K.; Lauffenburger, Douglas A.

    2011-01-01

    Predictive understanding of cell signaling network operation based on general prior knowledge but consistent with empirical data in a specific environmental context is a current challenge in computational biology. Recent work has demonstrated that Boolean logic can be used to create context-specific network models by training proteomic pathway maps to dedicated biochemical data; however, the Boolean formalism is restricted to characterizing protein species as either fully active or inactive. To advance beyond this limitation, we propose a novel form of fuzzy logic sufficiently flexible to model quantitative data but also sufficiently simple to efficiently construct models by training pathway maps on dedicated experimental measurements. Our new approach, termed constrained fuzzy logic (cFL), converts a prior knowledge network (obtained from literature or interactome databases) into a computable model that describes graded values of protein activation across multiple pathways. We train a cFL-converted network to experimental data describing hepatocytic protein activation by inflammatory cytokines and demonstrate the application of the resultant trained models for three important purposes: (a) generating experimentally testable biological hypotheses concerning pathway crosstalk, (b) establishing capability for quantitative prediction of protein activity, and (c) prediction and understanding of the cytokine release phenotypic response. Our methodology systematically and quantitatively trains a protein pathway map summarizing curated literature to context-specific biochemical data. This process generates a computable model yielding successful prediction of new test data and offering biological insight into complex datasets that are difficult to fully analyze by intuition alone. PMID:21408212

  19. [Biochemical changes in apoptosis and methods for their determination (review)].

    PubMed

    Sedláková, A; Kohút, A; Kalina, I

    1999-08-01

    Apoptosis or programmed cell death is a physiological process which occurs at different biological states as well as at disease process. Morphologically it is characterized by the chromatine condensation and other changes with preserved integrity of plasmatic membrane. The major and most frequently studied biochemical characteristic of apoptosis is a DNA fragmentation. In our paper attention is directed to the early biochemical changes in cell membranes, i.g., the externalization of phosphatidylserine, hydrolysis of sphingomyeline on the ceramide and activation of phospholipases especially phospholipase A2. In one part we described the changes of cysteine proteases (caspases), which play a key role in the execution of apoptosis. These biochemical changes are associated with ceramide signalization of apoptosis. Briefly are presented also some dates about apoptosis induction with reactive oxygen radicals and the role of the arachidonic acid metabolites in this process. We consider the investigation and determination of these changes as important parameters of apoptosis at some diseases, e.g., cancer or degenerative diseases, and of their treatment.

  20. Temperature-programmed natural convection for micromixing and biochemical reaction in a single microfluidic chamber.

    PubMed

    Kim, Sung-Jin; Wang, Fang; Burns, Mark A; Kurabayashi, Katsuo

    2009-06-01

    Micromixing is a crucial step for biochemical reactions in microfluidic networks. A critical challenge is that the system containing micromixers needs numerous pumps, chambers, and channels not only for the micromixing but also for the biochemical reactions and detections. Thus, a simple and compatible design of the micromixer element for the system is essential. Here, we propose a simple, yet effective, scheme that enables micromixing and a biochemical reaction in a single microfluidic chamber without using any pumps. We accomplish this process by using natural convection in conjunction with alternating heating of two heaters for efficient micromixing, and by regulating capillarity for sample transport. As a model application, we demonstrate micromixing and subsequent polymerase chain reaction (PCR) for an influenza viral DNA fragment. This process is achieved in a platform of a microfluidic cartridge and a microfabricated heating-instrument with a fast thermal response. Our results will significantly simplify micromixing and a subsequent biochemical reaction that involves reagent heating in microfluidic networks.

  1. Self-organizing ontology of biochemically relevant small molecules

    PubMed Central

    2012-01-01

    Background The advent of high-throughput experimentation in biochemistry has led to the generation of vast amounts of chemical data, necessitating the development of novel analysis, characterization, and cataloguing techniques and tools. Recently, a movement to publically release such data has advanced biochemical structure-activity relationship research, while providing new challenges, the biggest being the curation, annotation, and classification of this information to facilitate useful biochemical pattern analysis. Unfortunately, the human resources currently employed by the organizations supporting these efforts (e.g. ChEBI) are expanding linearly, while new useful scientific information is being released in a seemingly exponential fashion. Compounding this, currently existing chemical classification and annotation systems are not amenable to automated classification, formal and transparent chemical class definition axiomatization, facile class redefinition, or novel class integration, thus further limiting chemical ontology growth by necessitating human involvement in curation. Clearly, there is a need for the automation of this process, especially for novel chemical entities of biological interest. Results To address this, we present a formal framework based on Semantic Web technologies for the automatic design of chemical ontology which can be used for automated classification of novel entities. We demonstrate the automatic self-assembly of a structure-based chemical ontology based on 60 MeSH and 40 ChEBI chemical classes. This ontology is then used to classify 200 compounds with an accuracy of 92.7%. We extend these structure-based classes with molecular feature information and demonstrate the utility of our framework for classification of functionally relevant chemicals. Finally, we discuss an iterative approach that we envision for future biochemical ontology development. Conclusions We conclude that the proposed methodology can ease the burden of chemical data annotators and dramatically increase their productivity. We anticipate that the use of formal logic in our proposed framework will make chemical classification criteria more transparent to humans and machines alike and will thus facilitate predictive and integrative bioactivity model development. PMID:22221313

  2. Analysis of the coexisting pathways for NO and N2O formation in Chernozem using the (15)N-tracer SimKIM-Advanced model.

    PubMed

    Stange, Claus Florian; Spott, Oliver; Russow, Rolf

    2013-01-01

    The nitrogen (N) cycle consists of a variety of microbial processes. These processes often occur simultaneously in soils, but respond differently to local environmental conditions due to process-specific biochemical restrictions (e.g. oxygen levels). Hence, soil nitrogen cycling (e.g. soil N gas production through nitrification and denitrification) is individually affected through these processes, resulting in the complex and highly dynamic behaviour of total soil N turnover. The development and application of methods that facilitate the quantification of individual contributions of coexisting processes is a fundamental prerequisite for (i) understanding the dynamics of soil N turnover and (ii) implementing these processes in ecosystem models. To explain the unexpected results of the triplet tracer experiment (TTE) of Russow et al. (Role of nitrite and nitric oxide in the processes of nitrification and denitrification in soil: results from (15)N tracer experiments. Soil Biol Biochem. 2009;41:785-795) the existing SimKIM model was extended to the SimKIM-Advanced model through the addition of three separate nitrite subpools associated with ammonia oxidation, oxidation of organic nitrogen (Norg), and denitrification, respectively. For the TTE, individual treatments with (15)N ammonium, (15)N nitrate, and (15)N nitrite were conducted under oxic, hypoxic, and anoxic conditions, respectively, to clarify the role of nitric oxide as a denitrification intermediate during N2O formation. Using a split nitrite pool, this analysis model explains the observed differences in the (15)N enrichments in nitric oxide (NO) and nitrous oxide (N2O) which occurred in dependence on different oxygen concentrations. The change from oxic over hypoxic to anoxic conditions only marginally increased the NO and N2O release rates (1.3-fold). The analysis using the model revealed that, under oxic and hypoxic conditions, Norg-based N2O production was the dominant pathway, contributing to 90 and 50 % of the total soil N2O release. Under anoxic conditions, denitrification was the dominant process for soil N2O release. The relative contribution of Norg to the total soil NO release was small. Ammonia oxidation served as the major pathway of soil NO release under oxic and hypoxic conditions, while denitrification was dominant under anoxic conditions. The model parameters for soil with moderate soil organic matter (SOM) content were not scalable to an additional data set for soil with higher SOM content, indicating a strong influence of SOM content on microbial N turnover. Thus, parameter estimation had to be re-calculated for these conditions, highlighting the necessity of individual soil-dependent parameter estimations.

  3. Apparatus and method for converting biomass to feedstock for biofuel and biochemical manufacturing processes

    DOEpatents

    Kania, John; Qiao, Ming; Woods, Elizabeth M.; Cortright, Randy D.; Myren, Paul

    2015-12-15

    The present invention includes improved systems and methods for producing biomass-derived feedstocks for biofuel and biochemical manufacturing processes. The systems and methods use components that are capable of transferring relatively high concentrations of solid biomass utilizing pressure variations between vessels, and allows for the recovery and recycling of heterogeneous catalyst materials.

  4. Recent Advances on the Use of Biochemical Extracts as Filaricidal Agents

    PubMed Central

    Al-Abd, Nazeh M.; Nor, Zurainee Mohamed; Al-Adhroey, Abdulelah H.; Suhaimi, Anwar; Sivanandam, S.

    2013-01-01

    Lymphatic filariasis is a parasitic infection that causes a devastating public health and socioeconomic burden with an estimated infection of over 120 million individuals worldwide. The infection is caused by three closely related nematode parasites, namely, Wuchereria bancrofti, Brugia malayi, and B. timori, which are transmitted to human through mosquitoes of Anopheles, Culex, and Aedes genera. The species have many ecological variants and are diversified in terms of their genetic fingerprint. The rapid spread of the disease and the genetic diversification cause the lymphatic filarial parasites to respond differently to diagnostic and therapeutic interventions. This in turn prompts the current challenge encountered in its management. Furthermore, most of the chemical medications used are characterized by adverse side effects. These complications urgently warrant intense prospecting on bio-chemicals that have potent efficacy against either the filarial worms or thier vector. In lieu of this, we presented a review on recent literature that reported the efficacy of filaricidal biochemicals and those employed as vector control agents. In addition, methods used for biochemical extraction, screening procedures, and structure of the bioactive compounds were also presented. PMID:24298292

  5. In Vitro Modeling of Mechanics in Cancer Metastasis

    PubMed Central

    2017-01-01

    In addition to a multitude of genetic and biochemical alterations, abnormal morphological, structural, and mechanical changes in cells and their extracellular environment are key features of tumor invasion and metastasis. Furthermore, it is now evident that mechanical cues alongside biochemical signals contribute to critical steps of cancer initiation, progression, and spread. Despite its importance, it is very challenging to study mechanics of different steps of metastasis in the clinic or even in animal models. While considerable progress has been made in developing advanced in vitro models for studying genetic and biological aspects of cancer, less attention has been paid to models that can capture both biological and mechanical factors realistically. This is mainly due to lack of appropriate models and measurement tools. After introducing the central role of mechanics in cancer metastasis, we provide an outlook on the emergence of novel in vitro assays and their combination with advanced measurement technologies to probe and recapitulate mechanics in conditions more relevant to the metastatic disease. PMID:29457129

  6. Endosymbiotic associations within protists

    PubMed Central

    Nowack, Eva C. M.; Melkonian, Michael

    2010-01-01

    The establishment of an endosymbiotic relationship typically seems to be driven through complementation of the host's limited metabolic capabilities by the biochemical versatility of the endosymbiont. The most significant examples of endosymbiosis are represented by the endosymbiotic acquisition of plastids and mitochondria, introducing photosynthesis and respiration to eukaryotes. However, there are numerous other endosymbioses that evolved more recently and repeatedly across the tree of life. Recent advances in genome sequencing technology have led to a better understanding of the physiological basis of many endosymbiotic associations. This review focuses on endosymbionts in protists (unicellular eukaryotes). Selected examples illustrate the incorporation of various new biochemical functions, such as photosynthesis, nitrogen fixation and recycling, and methanogenesis, into protist hosts by prokaryotic endosymbionts. Furthermore, photosynthetic eukaryotic endosymbionts display a great diversity of modes of integration into different protist hosts. In conclusion, endosymbiosis seems to represent a general evolutionary strategy of protists to acquire novel biochemical functions and is thus an important source of genetic innovation. PMID:20124339

  7. Single molecule imaging of conformational dynamics in sodium-coupled transporters

    NASA Astrophysics Data System (ADS)

    Terry, Daniel S.

    Neurotransmitter:sodium symporter (NSS) proteins remove neurotransmitters released into the synapse through a transport process driven by the physiological sodium ion (Na+) gradient. NSSs for dopamine, noradrenaline, and serotonin are targeted by the psychostimulants cocaine and amphetamines, as well as by antidepressants. The crystal structure of LeuT, a prokaryotic NSS homologue, revealed the NSS molecular architecture and has been the basis for extensive structural, biochemical, and computational investigations of the mechanism of transporter proteins with a LeuT-like fold. In this dissertation, the conformational states sampled by LeuT are explored using single-molecule fluorescence resonance energy transfer imaging methods, with special focus on the motions of transmembrane helix 1a that lead to inward release of substrate. We also explored how dynamics are modulated by substrate, Na+, and protons to produce efficient transport. These advances represent a first of a kind study of the dynamics of an integral membrane protein at a truly single-molecule scale. Advances in instrumentation, analysis tools, and organic fluorophores were all required to achieve these goals, and such advances are also described. While these experiments were performed with detergent-solubilized protein, preliminary work suggests that imaging of LeuT in proteoliposomes is feasible and a fluorescence sensor assay could be used to simultaneously detect conformational dynamics and transport function.

  8. Recent advances in hydrogels for cartilage tissue engineering.

    PubMed

    Vega, S L; Kwon, M Y; Burdick, J A

    2017-01-30

    Articular cartilage is a load-bearing tissue that lines the surface of bones in diarthrodial joints. Unfortunately, this avascular tissue has a limited capacity for intrinsic repair. Treatment options for articular cartilage defects include microfracture and arthroplasty; however, these strategies fail to generate tissue that adequately restores damaged cartilage. Limitations of current treatments for cartilage defects have prompted the field of cartilage tissue engineering, which seeks to integrate engineering and biological principles to promote the growth of new cartilage to replace damaged tissue. To date, a wide range of scaffolds and cell sources have emerged with a focus on recapitulating the microenvironments present during development or in adult tissue, in order to induce the formation of cartilaginous constructs with biochemical and mechanical properties of native tissue. Hydrogels have emerged as a promising scaffold due to the wide range of possible properties and the ability to entrap cells within the material. Towards improving cartilage repair, hydrogel design has advanced in recent years to improve their utility. Some of these advances include the development of improved network crosslinking (e.g. double-networks), new techniques to process hydrogels (e.g. 3D printing) and better incorporation of biological signals (e.g. controlled release). This review summarises these innovative approaches to engineer hydrogels towards cartilage repair, with an eye towards eventual clinical translation.

  9. Advanced biomaterials and microengineering technologies to recapitulate the stepwise process of cancer metastasis.

    PubMed

    Peela, Nitish; Truong, Danh; Saini, Harpinder; Chu, Hunghao; Mashaghi, Samaneh; Ham, Stephanie L; Singh, Sunil; Tavana, Hossein; Mosadegh, Bobak; Nikkhah, Mehdi

    2017-07-01

    Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and adapt to a plethora of biochemical and biophysical signals from stromal cells and extracellular matrix (ECM) proteins. Due to these complexities, there is a critical need to understand molecular mechanisms underlying cancer metastasis to facilitate the discovery of more effective therapies. In the past few years, the integration of advanced biomaterials and microengineering approaches has initiated the development of innovative platform technologies for cancer research. These technologies enable the creation of biomimetic in vitro models with physiologically relevant (i.e. in vivo-like) characteristics to conduct studies ranging from fundamental cancer biology to high-throughput drug screening. In this review article, we discuss the biological significance of each step of the metastatic cascade and provide a broad overview on recent progress to recapitulate these stages using advanced biomaterials and microengineered technologies. In each section, we will highlight the advantages and shortcomings of each approach and provide our perspectives on future directions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. S-Nitrosothiols and the S-Nitrosoproteome of the Cardiovascular System

    PubMed Central

    Maron, Bradley A.; Tang, Shiow-Shih

    2013-01-01

    Abstract Significance: Since their discovery in the early 1990's, S-nitrosylated proteins have been increasingly recognized as important determinants of many biochemical processes. Specifically, S-nitrosothiols in the cardiovascular system exert many actions, including promoting vasodilation, inhibiting platelet aggregation, and regulating Ca2+ channel function that influences myocyte contractility and electrophysiologic stability. Recent Advances: Contemporary developments in liquid chromatography–mass spectrometry methods, the development of biotin- and His-tag switch assays, and the availability of cyanide dye-labeling for S-nitrosothiol detection in vitro have increased significantly the identification of a number of cardiovascular protein targets of S-nitrosylation in vivo. Critical Issues: Recent analyses using modern S-nitrosothiol detection techniques have revealed the mechanistic significance of S-nitrosylation to the pathophysiology of numerous cardiovascular diseases, including essential hypertension, pulmonary hypertension, ischemic heart disease, stroke, and congestive heart failure, among others. Future Directions: Despite enhanced insight into S-nitrosothiol biochemistry, translating these advances into beneficial pharmacotherapies for patients with cardiovascular diseases remains a primary as-yet unmet goal for investigators within the field. Antioxid. Redox Signal. 18, 270–287. PMID:22770551

  11. Ascorbate as a Biosynthetic Precursor in Plants

    PubMed Central

    Debolt, Seth; Melino, Vanessa; Ford, Christopher M.

    2007-01-01

    Background and Aims l-Ascorbate (vitamin C) has well-documented roles in many aspects of redox control and anti-oxidant activity in plant cells. This Botanical Briefing highlights recent developments in another aspect of l-ascorbate metabolism: its function as a precursor for specific processes in the biosynthesis of organic acids. Scope The Briefing provides a summary of recent advances in our understanding of l-ascorbate metabolism, covering biosynthesis, translocation and functional aspects. The role of l-ascorbate as a biosynthetic precursor in the formation of oxalic acid, l-threonic acid and l-tartaric acid is described, and progress in elaborating the mechanisms of the formation of these acids is reviewed. The potential conflict between the two roles of l-ascorbate in plant cells, functional and biosynthetic, is highlighted. Conclusions Recent advances in the understanding of l-ascorbate catabolism and the formation of oxalic and l-tartaric acids provide compelling evidence for a major role of l-ascorbate in plant metabolism. Combined experimental approaches, using classic biochemical and emerging ‘omics’ technologies, have provided recent insight to previously under-investigated areas. PMID:17098753

  12. Biophysics at the Boundaries: The Next Problem Sets

    NASA Astrophysics Data System (ADS)

    Skolnick, Malcolm

    2009-03-01

    The interface between physics and biology is one of the fastest growing subfields of physics. As knowledge of such topics as cellular processes and complex ecological systems advances, researchers have found that progress in understanding these and other systems requires application of more quantitative approaches. Today, there is a growing demand for quantitative and computational skills in biological research and the commercialization of that research. The fragmented teaching of science in our universities still leaves biology outside the quantitative and mathematical culture that is the foundation of physics. This is particularly inopportune at a time when the needs for quantitative thinking about biological systems are exploding. More physicists should be encouraged to become active in research and development in the growing application fields of biophysics including molecular genetics, biomedical imaging, tissue generation and regeneration, drug development, prosthetics, neural and brain function, kinetics of nonequilibrium open biological systems, metabolic networks, biological transport processes, large-scale biochemical networks and stochastic processes in biochemical systems to name a few. In addition to moving into basic research in these areas, there is increasing opportunity for physicists in industry beginning with entrepreneurial roles in taking research results out of the laboratory and in the industries who perfect and market the inventions and developments that physicists produce. In this talk we will identify and discuss emerging opportunities for physicists in biophysical and biotechnological pursuits ranging from basic research through development of applications and commercialization of results. This will include discussion of the roles of physicists in non-traditional areas apart from academia such as patent law, financial analysis and regulatory science and the problem sets assigned in education and training that will enable future biophysicists to fill these roles.

  13. Confocal Raman study of aging process in diabetes mellitus human voluntaries

    NASA Astrophysics Data System (ADS)

    Pereira, Liliane; Téllez Soto, Claudio Alberto; dos Santos, Laurita; Ali, Syed Mohammed; Fávero, Priscila Pereira; Martin, Airton A.

    2015-06-01

    Accumulation of AGEs [Advanced Glycation End - products] occurs slowly during the human aging process. However, its formation is accelerated in the presence of diabetes mellitus. In this paper, we perform a noninvasive analysis of glycation effect on human skin by in vivo confocal Raman spectroscopy. This technique uses a laser of 785 nm as excitation source and, by the inelastic scattering of light, it is possible to obtain information about the biochemical composition of the skin. Our aim in this work was to characterize the aging process resulting from the glycation process in a group of 10 Health Elderly Women (HEW) and 10 Diabetic Elderly Women (DEW). The Raman data were collected from the dermis at a depth of 70-130 microns. Through the theory of functional density (DFT) the bands positions of hydroxyproline, proline and AGEs (pentosidine and glucosepane) were calculated by using Gaussian 0.9 software. A molecular interpretation of changes in type I collagen was performed by the changes in the vibrational modes of the proline (P) and hydroxyproline (HP). The data analysis shows that the aging effects caused by glycation of proteins degrades type I collagen differently and leads to accelerated aging process.

  14. COLDEX-86: Fluid and Electrolyte Changes during Prolonged Cold Water Immersion

    DTIC Science & Technology

    1990-12-01

    4 Urine and blood collections .................. ..................... 5 Sample processing and biochemical analyses...and decaffeinated tea and coffee. Ingestion of fluids was encouraged. After completing the immersion, 16 oz of warm apple or cranberry juice was...day. Sample processing and biochemical analyses. Blood samples (25 ml) were drawn from an antecubital vein with minimum stasis. Each sample was divided

  15. Comparative genomics of a plant-parasitic nematode endosymbiont suggest a role in nutritional symbiosis

    USDA-ARS?s Scientific Manuscript database

    Bacterial mutualists can increase the biochemical capacity of animals. Highly co-evolved nutritional mutualists do this by synthesizing nutrients missing from the host's diet. Genomics tools have recently advanced the study of these partnerships. Here we examined the endosymbiont Xiphinematobacter (...

  16. Biosynthesis of a broad-spectrum nicotianamine-like metallophore in Staphylococcus aureus.

    PubMed

    Ghssein, Ghassan; Brutesco, Catherine; Ouerdane, Laurent; Fojcik, Clémentine; Izaute, Amélie; Wang, Shuanglong; Hajjar, Christine; Lobinski, Ryszard; Lemaire, David; Richaud, Pierre; Voulhoux, Romé; Espaillat, Akbar; Cava, Felipe; Pignol, David; Borezée-Durant, Elise; Arnoux, Pascal

    2016-05-27

    Metal acquisition is a vital microbial process in metal-scarce environments, such as inside a host. Using metabolomic exploration, targeted mutagenesis, and biochemical analysis, we discovered an operon in Staphylococcus aureus that encodes the different functions required for the biosynthesis and trafficking of a broad-spectrum metallophore related to plant nicotianamine (here called staphylopine). The biosynthesis of staphylopine reveals the association of three enzyme activities: a histidine racemase, an enzyme distantly related to nicotianamine synthase, and a staphylopine dehydrogenase belonging to the DUF2338 family. Staphylopine is involved in nickel, cobalt, zinc, copper, and iron acquisition, depending on the growth conditions. This biosynthetic pathway is conserved across other pathogens, thus underscoring the importance of this metal acquisition strategy in infection. Copyright © 2016, American Association for the Advancement of Science.

  17. Unexpected metastatic pheochromocytoma - an unusual presentation.

    PubMed

    Birrenbach, Tanja; Stanga, Zeno; Cottagnoud, Philippe; Stucki, Armin

    2008-01-01

    The classic triad of pheochromocytoma consists of episodic headache, sweating, and tachycardia. General clinicians should be aware, however, that this rare entity might present with a wide spectrum of clinical symptoms. We recently observed a noteworthy case of malignant pheochromocytoma where there was a lack of specific symptoms despite an advanced tumor stage. Malignancy is an important cause of mortality. Reliable diagnosis of malignancy depends upon evidence of local invasion, distant metastases, or recurrence. As in our case, new scintigraphic methods, such as 111-In-pentetreotide scintigraphy (Octreoscan), may occasionally reveal 123-I-metaiodobenzylguanidine-negative distant metastases and help to establish an early diagnosis of malignancy. Tumor size, and perhaps even biochemical profile, may be factors increasing the likelihood of a malignant process and may contribute to early identification of patients at risk.

  18. Pharmacotherapeutic targets in Alzheimer's disease

    PubMed Central

    Biran, Yif'at; Masters, Colin L; Barnham, Kevin J; Bush, Ashley I; Adlard, Paul A

    2009-01-01

    Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder which is characterized by an increasing impairment in normal memory and cognitive processes that significantly diminishes a person's daily functioning. Despite decades of research and advances in our understanding of disease aetiology and pathogenesis, there are still no effective disease-modifying drugs available for the treatment of AD. However, numerous compounds are currently undergoing pre-clinical and clinical evaluations. These candidate pharma-cotherapeutics are aimed at various aspects of the disease, such as the microtubule-associated τ-protein, the amyloid-β (Aβ) peptide and metal ion dyshomeostasis – all of which are involved in the development and progression of AD. We will review the way these pharmacological strategies target the biochemical and clinical features of the disease and the investigational drugs for each category. PMID:19040415

  19. Recent advances in pericentriolar material organization: ordered layers and scaffolding gels.

    PubMed

    Fry, Andrew M; Sampson, Josephina; Shak, Caroline; Shackleton, Sue

    2017-01-01

    The centrosome is an unusual organelle that lacks a surrounding membrane, raising the question of what limits its size and shape. Moreover, while electron microscopy (EM) has provided a detailed view of centriole architecture, there has been limited understanding of how the second major component of centrosomes, the pericentriolar material (PCM), is organized. Here, we summarize exciting recent findings from super-resolution fluorescence imaging, structural biology, and biochemical reconstitution that together reveal the presence of ordered layers and complex gel-like scaffolds in the PCM. Moreover, we discuss how this is leading to a better understanding of the process of microtubule nucleation, how alterations in PCM size are regulated in cycling and differentiated cells, and why mutations in PCM components lead to specific human pathologies.

  20. Recent advances in pericentriolar material organization: ordered layers and scaffolding gels

    PubMed Central

    Fry, Andrew M.; Sampson, Josephina; Shak, Caroline; Shackleton, Sue

    2017-01-01

    The centrosome is an unusual organelle that lacks a surrounding membrane, raising the question of what limits its size and shape. Moreover, while electron microscopy (EM) has provided a detailed view of centriole architecture, there has been limited understanding of how the second major component of centrosomes, the pericentriolar material (PCM), is organized. Here, we summarize exciting recent findings from super-resolution fluorescence imaging, structural biology, and biochemical reconstitution that together reveal the presence of ordered layers and complex gel-like scaffolds in the PCM. Moreover, we discuss how this is leading to a better understanding of the process of microtubule nucleation, how alterations in PCM size are regulated in cycling and differentiated cells, and why mutations in PCM components lead to specific human pathologies. PMID:29026530

  1. Thermodynamic considerations on Ca2+-induced biochemical reactions in living cells

    NASA Astrophysics Data System (ADS)

    Lucia, Umberto; Ponzetto, Antonio

    2016-02-01

    Cells can be regarded as complex engines that execute a series of chemical reactions. Energy transformations, thermo-electro-chemical processes and transport phenomena can occur across cell membranes. Different, related thermo-electro-biochemical behaviour can occur between health and disease states. Analysis of the irreversibility related to ion fluxes can represent a new approach to study and control the biochemical behaviour of living cells.

  2. Multimodal nanoparticle imaging agents: design and applications

    NASA Astrophysics Data System (ADS)

    Burke, Benjamin P.; Cawthorne, Christopher; Archibald, Stephen J.

    2017-10-01

    Molecular imaging, where the location of molecules or nanoscale constructs can be tracked in the body to report on disease or biochemical processes, is rapidly expanding to include combined modality or multimodal imaging. No single imaging technique can offer the optimum combination of properties (e.g. resolution, sensitivity, cost, availability). The rapid technological advances in hardware to scan patients, and software to process and fuse images, are pushing the boundaries of novel medical imaging approaches, and hand-in-hand with this is the requirement for advanced and specific multimodal imaging agents. These agents can be detected using a selection from radioisotope, magnetic resonance and optical imaging, among others. Nanoparticles offer great scope in this area as they lend themselves, via facile modification procedures, to act as multifunctional constructs. They have relevance as therapeutics and drug delivery agents that can be tracked by molecular imaging techniques with the particular development of applications in optically guided surgery and as radiosensitizers. There has been a huge amount of research work to produce nanoconstructs for imaging, and the parameters for successful clinical translation and validation of therapeutic applications are now becoming much better understood. It is an exciting time of progress for these agents as their potential is closer to being realized with translation into the clinic. The coming 5-10 years will be critical, as we will see if the predicted improvement in clinical outcomes becomes a reality. Some of the latest advances in combination modality agents are selected and the progression pathway to clinical trials analysed. This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

  3. Genetic resources for advanced biofuel production described with the Gene Ontology

    DOE PAGES

    Torto-Alalibo, Trudy; Purwantini, Endang; Lomax, Jane; ...

    2014-10-10

    Dramatic increases in research in the area of microbial biofuel production coupled with high-throughput data generation on bioenergy-related microbes has led to a deluge of information in the scientific literature and in databases. Consolidating this information and making it easily accessible requires a unified vocabulary.The Gene Ontology (GO) fulfills that requirement, as it is a well-developed structured vocabulary that describes the activities and locations of gene products in a consistent manner across all kingdoms of life. The Microbial ENergy processes Gene Ontology (http://www.mengo.biochem.vt.edu) project is extending the GO to include new terms to describe microbial processes of interest to bioenergymore » production. Our effort has added over 600 bioenergy related terms to the Gene Ontology. These terms will aid in the comprehensive annotation of gene products from diverse energy-related microbial genomes. An area of microbial energy research that has received a lot of attention is microbial production of advanced biofuels. These include alcohols such as butanol, isopropanol, isobutanol, and fuels derived from fatty acids, isoprenoids, and polyhydroxyalkanoates. These fuels are superior to first generation biofuels (ethanol and biodiesel esterified from vegetable oil or animal fat), can be generated from non-food feedstock sources, can be used as supplements or substitutes for gasoline, diesel and jet fuels, and can be stored and distributed using existing infrastructure. We review the roles of genes associated with synthesis of advanced biofuels, and at the same time introduce the use of the GO to describe the functions of these genes in a standardized way.« less

  4. Genetic resources for advanced biofuel production described with the Gene Ontology

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

    Torto-Alalibo, Trudy; Purwantini, Endang; Lomax, Jane

    Dramatic increases in research in the area of microbial biofuel production coupled with high-throughput data generation on bioenergy-related microbes has led to a deluge of information in the scientific literature and in databases. Consolidating this information and making it easily accessible requires a unified vocabulary.The Gene Ontology (GO) fulfills that requirement, as it is a well-developed structured vocabulary that describes the activities and locations of gene products in a consistent manner across all kingdoms of life. The Microbial ENergy processes Gene Ontology (http://www.mengo.biochem.vt.edu) project is extending the GO to include new terms to describe microbial processes of interest to bioenergymore » production. Our effort has added over 600 bioenergy related terms to the Gene Ontology. These terms will aid in the comprehensive annotation of gene products from diverse energy-related microbial genomes. An area of microbial energy research that has received a lot of attention is microbial production of advanced biofuels. These include alcohols such as butanol, isopropanol, isobutanol, and fuels derived from fatty acids, isoprenoids, and polyhydroxyalkanoates. These fuels are superior to first generation biofuels (ethanol and biodiesel esterified from vegetable oil or animal fat), can be generated from non-food feedstock sources, can be used as supplements or substitutes for gasoline, diesel and jet fuels, and can be stored and distributed using existing infrastructure. We review the roles of genes associated with synthesis of advanced biofuels, and at the same time introduce the use of the GO to describe the functions of these genes in a standardized way.« less

  5. Metabolomics Applications in Precision Medicine: An Oncological Perspective

    PubMed Central

    Puchades-Carrasco, Leonor; Pineda-Lucena, Antonio

    2017-01-01

    Nowadays, cancer therapy remains limited by the conventional one-size-fits-all approach. In this context, treatment decisions are based on the clinical stage of disease but fail to ascertain the individual´s underlying biology and its role in driving malignancy. The identification of better therapies for cancer treatment is thus limited by the lack of sufficient data regarding the characterization of specific biochemical signatures associated with each particular cancer patient or group of patients. Metabolomics approaches promise a better understanding of cancer, a disease characterized by significant alterations in bioenergetic metabolism, by identifying changes in the pattern of metabolite expression in addition to changes in the concentration of individual metabolites as well as alterations in biochemical pathways. These approaches hold the potential of identifying novel biomarkers with different clinical applications, including the development of more specific diagnostic methods based on the characterization of metabolic subtypes, the monitoring of currently used cancer therapeutics to evaluate the response and the prognostic outcome with a given therapy, and the evaluation of the mechanisms involved in disease relapse and drug resistance. This review discusses metabolomics applications in different oncological processes underlining the potential of this omics approach to further advance the implementation of precision medicine in the oncology area. PMID:28685691

  6. Integrating 'omic' data and biogeochemical modeling: the key to understanding the microbial regulation of matter cycling in soil

    NASA Astrophysics Data System (ADS)

    Pagel, Holger; Kandeler, Ellen; Seifert, Jana; Camarinha-Silva, Amélia; Kügler, Philipp; Rennert, Thilo; Poll, Christian; Streck, Thilo

    2016-04-01

    Matter cycling in soils and associated soil functions are intrinsically controlled by microbial dynamics. It is therefore crucial to consider functional traits of microorganisms in biogeochemical models. Tremendous advances in 'omic' methods provide a plethora of data on physiology, metabolic capabilities and ecological life strategies of microorganisms in soil. Combined with isotopic techniques, biochemical pathways and transformations can be identified and quantified. Such data have been, however, rarely used to improve the mechanistic representation of microbial dynamics in soil organic matter models. It is the goal of the Young Investigator Group SoilReg to address this challenge. Our general approach is to tightly integrate experiments and biochemical modeling. NextGen sequencing will be applied to identify key functional groups. Active microbial groups will be quantified by measurements of functional genes and by stable isotope probing methods of DNA and proteins. Based on this information a biogeochemical model that couples a mechanistic representation of microbial dynamics with physicochemical processes will be set up and calibrated. Sensitivity and stability analyses of the model as well as scenario simulations will reveal the importance of intrinsic and extrinsic controls of organic matter turnover. We will demonstrate our concept and present first results of two case studies on pesticide degradation and methane oxidation.

  7. Commercial processed soy-based food product contains glycated and glycoxidated lunasin proteoforms.

    PubMed

    Serra, Aida; Gallart-Palau, Xavier; See-Toh, Rachel Su-En; Hemu, Xinya; Tam, James P; Sze, Siu Kwan

    2016-05-18

    Nutraceuticals have been proposed to exert positive effects on human health and confer protection against many chronic diseases. A major bioactive component of soy-based foods is lunasin peptide, which has potential to exert a major impact on the health of human consumers worldwide, but the biochemical features of dietary lunasin still remain poorly characterized. In this study, lunasin was purified from a soy-based food product via strong anion exchange solid phase extraction and then subjected to top-down mass spectrometry analysis that revealed in detail the molecular diversity of lunasin in processed soybean foods. We detected multiple glycated proteoforms together with potentially toxic advanced glycation end products (AGEs) derived from lunasin. In both cases, modification sites were Lys24 and Lys29 located at the helical region that shows structural homology with a conserved region of chromatin-binding proteins. The identified post-translational modifications may have an important repercussion on lunasin epigenetic regulatory capacity. Taking together, our results demonstrate the importance of proper chemical characterization of commercial processed food products to assess their impact on consumer's health and risk of chronic diseases.

  8. Structural Basis for Guide RNA Processing and Seed-Dependent DNA Targeting by CRISPR-Cas12a.

    PubMed

    Swarts, Daan C; van der Oost, John; Jinek, Martin

    2017-04-20

    The CRISPR-associated protein Cas12a (Cpf1), which has been repurposed for genome editing, possesses two distinct nuclease activities: endoribonuclease activity for processing its own guide RNAs and RNA-guided DNase activity for target DNA cleavage. To elucidate the molecular basis of both activities, we determined crystal structures of Francisella novicida Cas12a bound to guide RNA and in complex with an R-loop formed by a non-cleavable guide RNA precursor and a full-length target DNA. Corroborated by biochemical experiments, these structures reveal the mechanisms of guide RNA processing and pre-ordering of the seed sequence in the guide RNA that primes Cas12a for target DNA binding. Furthermore, the R-loop complex structure reveals the strand displacement mechanism that facilitates guide-target hybridization and suggests a mechanism for double-stranded DNA cleavage involving a single active site. Together, these insights advance our mechanistic understanding of Cas12a enzymes and may contribute to further development of genome editing technologies. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Enhancement of sedimentation and coagulation with static magnetic field

    NASA Astrophysics Data System (ADS)

    Zieliński, Marcin; Dębowski, Marcin; Hajduk, Anna; Rusanowska, Paulina

    2017-11-01

    The static magnetic field can be an alternative method for wastewater treatment. It has been proved that this physical factor, accelerates the biochemical processes, catalyzes advanced oxidation, intensifies anaerobic and aerobic processes or reduces swelling of activated sludge. There are also reports proving the positive impact of the static magnetic field on the coagulation and sedimentation, as well as the conditioning and dewatering of sludge. In order to be applied in larger scale the published results should be verified and confirmed. In the studies, the enhancement of sedimentation by the static magnetic field was observed. The best sedimentation was noted in the experiment, where magnetizers were placed on activated sludge bioreactor and secondary settling tank. No effect of the static magnetic field on coagulation with the utilization of PIX 113 was observed. However, the static magnetic field enhanced coagulation with the utilization of PAX-XL9. The results suggest that increased sedimentation of colloids and activated sludge, can in practice mean a reduction in the size of the necessary equipment for sedimentation with an unchanged efficiency of the process.

  10. Commercial processed soy-based food product contains glycated and glycoxidated lunasin proteoforms

    PubMed Central

    Serra, Aida; Gallart-Palau, Xavier; See-Toh, Rachel Su-En; Hemu, Xinya; Tam, James P.; Sze, Siu Kwan

    2016-01-01

    Nutraceuticals have been proposed to exert positive effects on human health and confer protection against many chronic diseases. A major bioactive component of soy-based foods is lunasin peptide, which has potential to exert a major impact on the health of human consumers worldwide, but the biochemical features of dietary lunasin still remain poorly characterized. In this study, lunasin was purified from a soy-based food product via strong anion exchange solid phase extraction and then subjected to top-down mass spectrometry analysis that revealed in detail the molecular diversity of lunasin in processed soybean foods. We detected multiple glycated proteoforms together with potentially toxic advanced glycation end products (AGEs) derived from lunasin. In both cases, modification sites were Lys24 and Lys29 located at the helical region that shows structural homology with a conserved region of chromatin-binding proteins. The identified post-translational modifications may have an important repercussion on lunasin epigenetic regulatory capacity. Taking together, our results demonstrate the importance of proper chemical characterization of commercial processed food products to assess their impact on consumer’s health and risk of chronic diseases. PMID:27189269

  11. Potential Tools for Phenotyping for Physical Characteristics of Plants, Pods, and Seed

    USDA-ARS?s Scientific Manuscript database

    Advances in phenotyping are a key factor for success in modern breeding as well as for basic plant research. Phenotyping provides a critical means to understand morphological, biochemical, physiological principles in the control of basic plant functions as well as for selecting superior genotypes in...

  12. Complete integrability of information processing by biochemical reactions

    PubMed Central

    Agliari, Elena; Barra, Adriano; Dello Schiavo, Lorenzo; Moro, Antonio

    2016-01-01

    Statistical mechanics provides an effective framework to investigate information processing in biochemical reactions. Within such framework far-reaching analogies are established among (anti-) cooperative collective behaviors in chemical kinetics, (anti-)ferromagnetic spin models in statistical mechanics and operational amplifiers/flip-flops in cybernetics. The underlying modeling – based on spin systems – has been proved to be accurate for a wide class of systems matching classical (e.g. Michaelis–Menten, Hill, Adair) scenarios in the infinite-size approximation. However, the current research in biochemical information processing has been focusing on systems involving a relatively small number of units, where this approximation is no longer valid. Here we show that the whole statistical mechanical description of reaction kinetics can be re-formulated via a mechanical analogy – based on completely integrable hydrodynamic-type systems of PDEs – which provides explicit finite-size solutions, matching recently investigated phenomena (e.g. noise-induced cooperativity, stochastic bi-stability, quorum sensing). The resulting picture, successfully tested against a broad spectrum of data, constitutes a neat rationale for a numerically effective and theoretically consistent description of collective behaviors in biochemical reactions. PMID:27812018

  13. Complete integrability of information processing by biochemical reactions

    NASA Astrophysics Data System (ADS)

    Agliari, Elena; Barra, Adriano; Dello Schiavo, Lorenzo; Moro, Antonio

    2016-11-01

    Statistical mechanics provides an effective framework to investigate information processing in biochemical reactions. Within such framework far-reaching analogies are established among (anti-) cooperative collective behaviors in chemical kinetics, (anti-)ferromagnetic spin models in statistical mechanics and operational amplifiers/flip-flops in cybernetics. The underlying modeling - based on spin systems - has been proved to be accurate for a wide class of systems matching classical (e.g. Michaelis-Menten, Hill, Adair) scenarios in the infinite-size approximation. However, the current research in biochemical information processing has been focusing on systems involving a relatively small number of units, where this approximation is no longer valid. Here we show that the whole statistical mechanical description of reaction kinetics can be re-formulated via a mechanical analogy - based on completely integrable hydrodynamic-type systems of PDEs - which provides explicit finite-size solutions, matching recently investigated phenomena (e.g. noise-induced cooperativity, stochastic bi-stability, quorum sensing). The resulting picture, successfully tested against a broad spectrum of data, constitutes a neat rationale for a numerically effective and theoretically consistent description of collective behaviors in biochemical reactions.

  14. Complete integrability of information processing by biochemical reactions.

    PubMed

    Agliari, Elena; Barra, Adriano; Dello Schiavo, Lorenzo; Moro, Antonio

    2016-11-04

    Statistical mechanics provides an effective framework to investigate information processing in biochemical reactions. Within such framework far-reaching analogies are established among (anti-) cooperative collective behaviors in chemical kinetics, (anti-)ferromagnetic spin models in statistical mechanics and operational amplifiers/flip-flops in cybernetics. The underlying modeling - based on spin systems - has been proved to be accurate for a wide class of systems matching classical (e.g. Michaelis-Menten, Hill, Adair) scenarios in the infinite-size approximation. However, the current research in biochemical information processing has been focusing on systems involving a relatively small number of units, where this approximation is no longer valid. Here we show that the whole statistical mechanical description of reaction kinetics can be re-formulated via a mechanical analogy - based on completely integrable hydrodynamic-type systems of PDEs - which provides explicit finite-size solutions, matching recently investigated phenomena (e.g. noise-induced cooperativity, stochastic bi-stability, quorum sensing). The resulting picture, successfully tested against a broad spectrum of data, constitutes a neat rationale for a numerically effective and theoretically consistent description of collective behaviors in biochemical reactions.

  15. Challenging Density Functional Theory Calculations with Hemes and Porphyrins

    PubMed Central

    de Visser, Sam P.; Stillman, Martin J.

    2016-01-01

    In this paper we review recent advances in computational chemistry and specifically focus on the chemical description of heme proteins and synthetic porphyrins that act as both mimics of natural processes and technological uses. These are challenging biochemical systems involved in electron transfer as well as biocatalysis processes. In recent years computational tools have improved considerably and now can reproduce experimental spectroscopic and reactivity studies within a reasonable error margin (several kcal·mol−1). This paper gives recent examples from our groups, where we investigated heme and synthetic metal-porphyrin systems. The four case studies highlight how computational modelling can correctly reproduce experimental product distributions, predicted reactivity trends and guide interpretation of electronic structures of complex systems. The case studies focus on the calculations of a variety of spectroscopic features of porphyrins and show how computational modelling gives important insight that explains the experimental spectra and can lead to the design of porphyrins with tuned properties. PMID:27070578

  16. Phosphoproteomics in bacteria: towards a systemic understanding of bacterial phosphorylation networks.

    PubMed

    Jers, Carsten; Soufi, Boumediene; Grangeasse, Christophe; Deutscher, Josef; Mijakovic, Ivan

    2008-08-01

    Bacteria use protein phosphorylation to regulate all kinds of physiological processes. Protein phosphorylation plays a role in several key steps of the infection process of bacterial pathogens, such as adhesion to the host, triggering and regulation of pathogenic functions as well as biochemical warfare; scrambling the host signaling cascades and impairing its defense mechanisms. Recent phosphoproteomic studies indicate that the bacterial protein phosphorylation networks could be more complex than initially expected, comprising promiscuous kinases that regulate several distinct cellular functions by phosphorylating different protein substrates. Recent advances in protein labeling with stable isotopes in the field of quantitative mass spectrometry phosphoproteomics will enable us to chart the global phosphorylation networks and to understand the implication of protein phosphorylation in cellular regulation on the systems scale. For the study of bacterial pathogens, in particular, this research avenue will enable us to dissect phosphorylation-related events during different stages of infection and stimulate our efforts to find inhibitors for key kinases and phosphatases implicated therein.

  17. Potential of PET-MRI for imaging of non-oncologic musculoskeletal disease.

    PubMed

    Kogan, Feliks; Fan, Audrey P; Gold, Garry E

    2016-12-01

    Early detection of musculoskeletal disease leads to improved therapies and patient outcomes, and would benefit greatly from imaging at the cellular and molecular level. As it becomes clear that assessment of multiple tissues and functional processes are often necessary to study the complex pathogenesis of musculoskeletal disorders, the role of multi-modality molecular imaging becomes increasingly important. New positron emission tomography-magnetic resonance imaging (PET-MRI) systems offer to combine high-resolution MRI with simultaneous molecular information from PET to study the multifaceted processes involved in numerous musculoskeletal disorders. In this article, we aim to outline the potential clinical utility of hybrid PET-MRI to these non-oncologic musculoskeletal diseases. We summarize current applications of PET molecular imaging in osteoarthritis (OA), rheumatoid arthritis (RA), metabolic bone diseases and neuropathic peripheral pain. Advanced MRI approaches that reveal biochemical and functional information offer complementary assessment in soft tissues. Additionally, we discuss technical considerations for hybrid PET-MR imaging including MR attenuation correction, workflow, radiation dose, and quantification.

  18. Synaptogenesis and heritable aspects of executive attention.

    PubMed

    Fossella, John A; Sommer, Tobias; Fan, Jin; Pfaff, Don; Posner, Michael I

    2003-01-01

    In humans, changes in brain structure and function can be measured non-invasively during postnatal development. In animals, advanced optical imaging measures can track the formation of synapses during learning and behavior. With the recent progress in these technologies, it is appropriate to begin to assess how the physiological processes of synapse, circuit, and neural network formation relate to the process of cognitive development. Of particular interest is the development of executive function, which develops more gradually in humans. One approach that has shown promise is molecular genetics. The completion of the human genome project and the human genome diversity project make it straightforward to ask whether variation in a particular gene correlates with variation in behavior, brain structure, brain activity, or all of the above. Strategies that unify the wealth of biochemical knowledge pertaining to synapse formation with the functional measures of brain structure and activity may lead to new insights in developmental cognitive psychology. Copyright 2003 Wiley-Liss, Inc.

  19. Marker-assisted selection in plant breeding for salinity tolerance.

    PubMed

    Ashraf, M; Akram, N A; Mehboob-Ur-Rahman; Foolad, M R

    2012-01-01

    Marker-assisted selection (MAS) is the process of using morphological, biochemical, or DNA markers as indirect selection criteria for selecting agriculturally important traits in crop breeding. This process is used to improve the effectiveness or efficiency of selection for the traits of interest in breeding programs. The significance of MAS as a tool for crop improvement has been extensively investigated in different crop -species and for different traits. The use of MAS for manipulating simple/qualitative traits is straightforward and has been well reported. However, MAS for the improvement of complex/polygenic traits, including plant tolerance/resistance to abiotic stresses, is more complicated, although its usefulness has been recognized. With the recent advances in marker technology, including high-throughput genotyping of plants, together with the development of nested association mapping populations, it is expected that the utility of MAS for breeding for stress tolerance traits will increase. In this chapter, we describe the basic procedure for using MAS in crop breeding for salt tolerance.

  20. Network news: prime time for systems biology of the plant circadian clock.

    PubMed

    McClung, C Robertson; Gutiérrez, Rodrigo A

    2010-12-01

    Whole-transcriptome analyses have established that the plant circadian clock regulates virtually every plant biological process and most prominently hormonal and stress response pathways. Systems biology efforts have successfully modeled the plant central clock machinery and an iterative process of model refinement and experimental validation has contributed significantly to the current view of the central clock machinery. The challenge now is to connect this central clock to the output pathways for understanding how the plant circadian clock contributes to plant growth and fitness in a changing environment. Undoubtedly, systems approaches will be needed to integrate and model the vastly increased volume of experimental data in order to extract meaningful biological information. Thus, we have entered an era of systems modeling, experimental testing, and refinement. This approach, coupled with advances from the genetic and biochemical analyses of clock function, is accelerating our progress towards a comprehensive understanding of the plant circadian clock network. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Putting together phylogenetic and ontogenetic perspectives on empathy.

    PubMed

    Decety, Jean; Svetlova, Margarita

    2012-01-01

    The ontogeny of human empathy is better understood with reference to the evolutionary history of the social brain. Empathy has deep evolutionary, biochemical, and neurological underpinnings. Even the most advanced forms of empathy in humans are built on more basic forms and remain connected to core mechanisms associated with affective communication, social attachment, and parental care. In this paper, we argue that it is essential to consider empathy within a neurodevelopmental framework that recognizes both the continuities and changes in socioemotional understanding from infancy to adulthood. We bring together neuroevolutionary and developmental perspectives on the information processing and neural mechanisms underlying empathy and caring, and show that they are grounded in multiple interacting systems and processes. Moreover, empathy in humans is assisted by other abstract and domain-general high-level cognitive abilities such as executive functions, mentalizing and language, as well as the ability to differentiate another's mental states from one's own, which expand the range of behaviors that can be driven by empathy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Microbial enhancement of oil recovery: Recent advances

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

    Premuzic, E.T.; Woodhead, A.D.; Vivirito, K.J.

    1992-01-01

    During recent years, systematic, scientific, and engineering effort by researchers in the United States and abroad, has established the scientific basis for Microbial Enhanced Oil Recovery (MEOR) technology. The successful application of MEOR technology as an oil recovery process is a goal of the Department of Energy (DOE). Research efforts involving aspects of MEOR in the microbiological, biochemical, and engineering fields led DOE to sponsor an International Conference at Brookhaven National Laboratory in 1992, to facilitate the exchange of information and a discussion of ideas for the future research emphasis. At this, the Fourth International MEOR Conference, where international attendeesmore » from 12 countries presented a total of 35 papers, participants saw an equal distribution between research'' and field applications.'' In addition, several modeling and state-of-the-art'' presentations summed up the present status of MEOR science and engineering. Individual papers in this proceedings have been process separately for inclusion in the Energy Science and Technology Database.« less

  3. Microbial enhancement of oil recovery: Recent advances. Proceedings

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

    Premuzic, E.T.; Woodhead, A.D.; Vivirito, K.J.

    1992-12-31

    During recent years, systematic, scientific, and engineering effort by researchers in the United States and abroad, has established the scientific basis for Microbial Enhanced Oil Recovery (MEOR) technology. The successful application of MEOR technology as an oil recovery process is a goal of the Department of Energy (DOE). Research efforts involving aspects of MEOR in the microbiological, biochemical, and engineering fields led DOE to sponsor an International Conference at Brookhaven National Laboratory in 1992, to facilitate the exchange of information and a discussion of ideas for the future research emphasis. At this, the Fourth International MEOR Conference, where international attendeesmore » from 12 countries presented a total of 35 papers, participants saw an equal distribution between ``research`` and ``field applications.`` In addition, several modeling and ``state-of-the-art`` presentations summed up the present status of MEOR science and engineering. Individual papers in this proceedings have been process separately for inclusion in the Energy Science and Technology Database.« less

  4. Advanced Technologies for Space Life Science Payloads on the International Space Station

    NASA Technical Reports Server (NTRS)

    Hines, John W.; Connolly, John P. (Technical Monitor)

    1997-01-01

    SENSORS 2000! (S2K!) is a specialized, high-performance work group organized to provide advanced engineering and technology support for NASA's Life Sciences spaceflight and ground-based research and development programs. In support of these objectives, S2K! manages NASA's Advanced Technology Development Program for Biosensor and Biotelemetry Systems (ATD-B), with particular emphasis on technologies suitable for Gravitational Biology, Human Health and Performance, and Information Technology and Systems Management. A concurrent objective is to apply and transition ATD-B developed technologies to external, non-NASA humanitarian (medical, clinical, surgical, and emergency) situations and to stimulate partnering and leveraging with other government agencies, academia, and the commercial/industrial sectors. A phased long-term program has been implemented to support science disciplines and programs requiring specific biosensor (i.e., biopotential, biophysical, biochemical, and biological) measurements from humans, animals (mainly primates and rodents), and cells under controlled laboratory and simulated microgravity situations. In addition to the technology programs described above, NASA's Life and Microgravity Sciences and Applications Office has initiated a Technology Infusion process to identify and coordinate the utilization and integration of advanced technologies into its International Space Station Facilities. This project has recently identified a series of technologies, tasks, and products which, if implemented, would significantly increase the science return, decrease costs, and provide improved technological capability. This presentation will review the programs described above and discuss opportunities for collaboration, leveraging, and partnering with NASA.

  5. Changes in composition of cuticular biochemicals of the facultatively polygynous ant Petalomyrmex phylax during range expansion in Cameroon with respect to social, spatial and genetic variation.

    PubMed

    Dalecky, Ambroise; Renucci, Marielle; Tirard, Alain; Debout, Gabriel; Roux, Maurice; Kjellberg, Finn; Provost, Erick

    2007-09-01

    In social insects, biochemicals found at the surface of the cuticle are involved in the recognition process and in protection against desiccation and pathogens. However, the relative contribution of evolutionary forces in shaping diversity of these biochemicals remains largely unresolved in ants. We determined the composition of epicuticular biochemicals for workers sampled in 12 populations of the ant Petalomyrmex phylax from Cameroon. Genetic variation at 12 microsatellite markers was used to infer population history and to provide null expectations under the neutrality hypothesis. Genetic data suggest a recent southward range expansion of this ant species. Furthermore, there is a decline southward in the numbers of queens present in mature colonies. Here, we contrast the pattern of biochemical variation against genetic, social and spatial parameters. We thus provide the first estimates of the relative contribution of neutral and selective processes on variation of ant cuticular profile. Populations in migration-drift disequilibrium showed reduction of within-population variation for genetic markers as well as for cuticular profiles. In these populations, the cuticular profile became biased towards a limited number of high molecular weight molecules. Within- and among-population biochemical variation was explained by both genetic and social variation and by the spatial distribution of populations. We therefore propose that during range expansion of P. phylax, the composition of epicuticular compounds has been affected by a combination of neutral processes - genetic drift and spatially limited dispersal - and spatially varying selection, social organization and environmental effects.

  6. Computational Cellular Dynamics Based on the Chemical Master Equation: A Challenge for Understanding Complexity

    PubMed Central

    Liang, Jie; Qian, Hong

    2010-01-01

    Modern molecular biology has always been a great source of inspiration for computational science. Half a century ago, the challenge from understanding macromolecular dynamics has led the way for computations to be part of the tool set to study molecular biology. Twenty-five years ago, the demand from genome science has inspired an entire generation of computer scientists with an interest in discrete mathematics to join the field that is now called bioinformatics. In this paper, we shall lay out a new mathematical theory for dynamics of biochemical reaction systems in a small volume (i.e., mesoscopic) in terms of a stochastic, discrete-state continuous-time formulation, called the chemical master equation (CME). Similar to the wavefunction in quantum mechanics, the dynamically changing probability landscape associated with the state space provides a fundamental characterization of the biochemical reaction system. The stochastic trajectories of the dynamics are best known through the simulations using the Gillespie algorithm. In contrast to the Metropolis algorithm, this Monte Carlo sampling technique does not follow a process with detailed balance. We shall show several examples how CMEs are used to model cellular biochemical systems. We shall also illustrate the computational challenges involved: multiscale phenomena, the interplay between stochasticity and nonlinearity, and how macroscopic determinism arises from mesoscopic dynamics. We point out recent advances in computing solutions to the CME, including exact solution of the steady state landscape and stochastic differential equations that offer alternatives to the Gilespie algorithm. We argue that the CME is an ideal system from which one can learn to understand “complex behavior” and complexity theory, and from which important biological insight can be gained. PMID:24999297

  7. Computational Cellular Dynamics Based on the Chemical Master Equation: A Challenge for Understanding Complexity.

    PubMed

    Liang, Jie; Qian, Hong

    2010-01-01

    Modern molecular biology has always been a great source of inspiration for computational science. Half a century ago, the challenge from understanding macromolecular dynamics has led the way for computations to be part of the tool set to study molecular biology. Twenty-five years ago, the demand from genome science has inspired an entire generation of computer scientists with an interest in discrete mathematics to join the field that is now called bioinformatics. In this paper, we shall lay out a new mathematical theory for dynamics of biochemical reaction systems in a small volume (i.e., mesoscopic) in terms of a stochastic, discrete-state continuous-time formulation, called the chemical master equation (CME). Similar to the wavefunction in quantum mechanics, the dynamically changing probability landscape associated with the state space provides a fundamental characterization of the biochemical reaction system. The stochastic trajectories of the dynamics are best known through the simulations using the Gillespie algorithm. In contrast to the Metropolis algorithm, this Monte Carlo sampling technique does not follow a process with detailed balance. We shall show several examples how CMEs are used to model cellular biochemical systems. We shall also illustrate the computational challenges involved: multiscale phenomena, the interplay between stochasticity and nonlinearity, and how macroscopic determinism arises from mesoscopic dynamics. We point out recent advances in computing solutions to the CME, including exact solution of the steady state landscape and stochastic differential equations that offer alternatives to the Gilespie algorithm. We argue that the CME is an ideal system from which one can learn to understand "complex behavior" and complexity theory, and from which important biological insight can be gained.

  8. Application of Biomarkers in the Development of Drugs Intended for the Treatment of Osteoarthritis

    PubMed Central

    Kraus, Virginia Byers; Burnett, Bruce; Coindreau, Javier; Cottrell, Susan; Eyre, David; Gendreau, Michael; Gardiner, Jennifer; Garnero, Patrick; Hardin, John; Henrotin, Yves; Heinegård, Dick; Ko, Amy; Lohmander, Stefan; Matthews, Gloria; Menetski, Joseph; Moskowitz, Roland; Persiani, Stefano; Poole, Robin; Rousseau, Jean Charles; Todman, Martin

    2013-01-01

    Objective Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal. Methods The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007–2009 at the behest of the Osteoarthritis Research Society International (OARSI FDA initiative). Results This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers. Conclusions Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within one to two years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent. PMID:21396468

  9. Modern collagen wound dressings: function and purpose.

    PubMed

    Fleck, Cynthia Ann; Simman, Richard

    2010-09-01

    Collagen, which is produced by fibroblasts, is the most abundant protein in the human body. A natural structural protein, collagen is involved in all 3 phases of the wound-healing cascade. It stimulates cellular migration and contributes to new tissue development. Because of their chemotactic properties on wound fibroblasts, collagen dressings encourage the deposition and organization of newly formed collagen, creating an environment that fosters healing. Collagen-based biomaterials stimulate and recruit specific cells, such as macrophages and fibroblasts, along the healing cascade to enhance and influence wound healing. These biomaterials can provide moisture or absorption, depending on the delivery system. Collagen dressings are easy to apply and remove and are conformable. Collagen dressings are usually formulated with bovine, avian, or porcine collagen. Oxidized regenerated cellulose, a plant-based material, has been combined with collagen to produce a dressing capable of binding to and protecting growth factors by binding and inactivating matrix metalloproteinases in the wound environment. The increased understanding of the biochemical processes involved in chronic wound healing allows the design of wound care products aimed at correcting imbalances in the wound microenvironment. Traditional advanced wound care products tend to address the wound's macroenvironment, including moist wound environment control, fluid management, and controlled transpiration of wound fluids. The newer class of biomaterials and wound-healing agents, such as collagen and growth factors, targets specific defects in the chronic wound environment. In vitro laboratory data point to the possibility that these agents benefit the wound healing process at a biochemical level. Considerable evidence has indicated that collagen-based dressings may be capable of stimulating healing by manipulating wound biochemistry.

  10. An Intelligent Automation Platform for Rapid Bioprocess Design.

    PubMed

    Wu, Tianyi; Zhou, Yuhong

    2014-08-01

    Bioprocess development is very labor intensive, requiring many experiments to characterize each unit operation in the process sequence to achieve product safety and process efficiency. Recent advances in microscale biochemical engineering have led to automated experimentation. A process design workflow is implemented sequentially in which (1) a liquid-handling system performs high-throughput wet lab experiments, (2) standalone analysis devices detect the data, and (3) specific software is used for data analysis and experiment design given the user's inputs. We report an intelligent automation platform that integrates these three activities to enhance the efficiency of such a workflow. A multiagent intelligent architecture has been developed incorporating agent communication to perform the tasks automatically. The key contribution of this work is the automation of data analysis and experiment design and also the ability to generate scripts to run the experiments automatically, allowing the elimination of human involvement. A first-generation prototype has been established and demonstrated through lysozyme precipitation process design. All procedures in the case study have been fully automated through an intelligent automation platform. The realization of automated data analysis and experiment design, and automated script programming for experimental procedures has the potential to increase lab productivity. © 2013 Society for Laboratory Automation and Screening.

  11. An Intelligent Automation Platform for Rapid Bioprocess Design

    PubMed Central

    Wu, Tianyi

    2014-01-01

    Bioprocess development is very labor intensive, requiring many experiments to characterize each unit operation in the process sequence to achieve product safety and process efficiency. Recent advances in microscale biochemical engineering have led to automated experimentation. A process design workflow is implemented sequentially in which (1) a liquid-handling system performs high-throughput wet lab experiments, (2) standalone analysis devices detect the data, and (3) specific software is used for data analysis and experiment design given the user’s inputs. We report an intelligent automation platform that integrates these three activities to enhance the efficiency of such a workflow. A multiagent intelligent architecture has been developed incorporating agent communication to perform the tasks automatically. The key contribution of this work is the automation of data analysis and experiment design and also the ability to generate scripts to run the experiments automatically, allowing the elimination of human involvement. A first-generation prototype has been established and demonstrated through lysozyme precipitation process design. All procedures in the case study have been fully automated through an intelligent automation platform. The realization of automated data analysis and experiment design, and automated script programming for experimental procedures has the potential to increase lab productivity. PMID:24088579

  12. A Preliminary Assessment of HTST Processing on Donkey Milk

    PubMed Central

    Antoniazzi, Sara; Gariglio, Gian Marco; Coscia, Alessandra; Bertino, Enrico; Cavallarin, Laura

    2017-01-01

    Due to increasing attention from consumers on non-bovine milk types, and to the increase in the number of small dairy donkey farms in Italy, farmers require more advanced and reliable processing devices, in order to guarantee a safe product of high quality. To this aim, a new small-scale High-Temperature Short-Time (HTST) pasteurizer (72 °C for 15 s), prototyped by the authors, was tested on donkey milk. The efficacy of the HTST device was tested on raw donkey milk microflora by enumeration of total aerobic bacteria, Enterobacteriaceae and Bacillus cereus. The biochemical quality was assessed by determining the protein profile by monodimensional electrophoresis and by measuring lysozyme activity. The HTST apparatus was able to reduce the total bacteria count, and to completely eradicate Enterobacteriaceae. Bacillus cereus, when present, was decreased with low efficiency. Changes in the protein profile were observed in milk pasteurized in accordance with both processes, although HTST seemed to limit casein degradation. Lysozyme activity was not substantially affected in comparison to raw donkey milk. In conclusion, a tailored small-volume HTST device could be safely applied to pasteurize donkey milk in on-farm pasteurization processes on small dairy donkey farms. PMID:29056708

  13. A Preliminary Assessment of HTST Processing on Donkey Milk.

    PubMed

    Giribaldi, Marzia; Antoniazzi, Sara; Gariglio, Gian Marco; Coscia, Alessandra; Bertino, Enrico; Cavallarin, Laura

    2017-10-09

    Due to increasing attention from consumers on non-bovine milk types, and to the increase in the number of small dairy donkey farms in Italy, farmers require more advanced and reliable processing devices, in order to guarantee a safe product of high quality. To this aim, a new small-scale High-Temperature Short-Time (HTST) pasteurizer (72 °C for 15 s), prototyped by the authors, was tested on donkey milk. The efficacy of the HTST device was tested on raw donkey milk microflora by enumeration of total aerobic bacteria, Enterobacteriaceae and Bacillus cereus. The biochemical quality was assessed by determining the protein profile by monodimensional electrophoresis and by measuring lysozyme activity. The HTST apparatus was able to reduce the total bacteria count, and to completely eradicate Enterobacteriaceae. Bacillus cereus, when present, was decreased with low efficiency. Changes in the protein profile were observed in milk pasteurized in accordance with both processes, although HTST seemed to limit casein degradation. Lysozyme activity was not substantially affected in comparison to raw donkey milk. In conclusion, a tailored small-volume HTST device could be safely applied to pasteurize donkey milk in on-farm pasteurization processes on small dairy donkey farms.

  14. Research advance of stability mechanism on physicochemical, biochemical and microorganism trait of wine

    NASA Astrophysics Data System (ADS)

    Nan, Lijun; Li, Yashan; Cui, Changwei; Ning, Na; Huang, Jing; Xu, Chengdong; Zhang, Xiaofang; Yang, Ruiqun; Zhong, Yingxue

    2018-04-01

    The stability of wine is an important feature during the wine aging, which is mainly reflected in the balance of color, taste and aroma during the wine aging. During the wine fermentation, the role of microbes and enzymes including the interaction between them caused the mutual penetration, combination, decomposition and transformation among the substances in connection with color, aroma and taste in wine, which led to the instability of wine. After the fermentation of wine, the long aging period could just stabilize the wine. Still, the quality of wine had changed a lot. Based on the indicative changes in wine, such as microbiological interactions, biochemical reactions as well as interactions between the microorganism and biochemical reactions, the impact of changes of the basic biochemical and physicochemical indices on the stability of red wine were reviewed, and developmental suggestions in the future were also put forward in this paper, in order to reveal the mechanism of instability through the effect of dynamic change on the stability of red wine and analyze the unstable root of the red wine, which could lay a foundation for further research, and provide help for actual production.

  15. Recent Advances in Nanobiotechnology and High-Throughput Molecular Techniques for Systems Biomedicine

    PubMed Central

    Kim, Eung-Sam; Ahn, Eun Hyun; Chung, Euiheon; Kim, Deok-Ho

    2013-01-01

    Nanotechnology-based tools are beginning to emerge as promising platforms for quantitative high-throughput analysis of live cells and tissues. Despite unprecedented progress made over the last decade, a challenge still lies in integrating emerging nanotechnology-based tools into macroscopic biomedical apparatuses for practical purposes in biomedical sciences. In this review, we discuss the recent advances and limitations in the analysis and control of mechanical, biochemical, fluidic, and optical interactions in the interface areas of nanotechnology-based materials and living cells in both in vitro and in vivo settings. PMID:24258011

  16. Recent advances in nanobiotechnology and high-throughput molecular techniques for systems biomedicine.

    PubMed

    Kim, Eung-Sam; Ahn, Eun Hyun; Chung, Euiheon; Kim, Deok-Ho

    2013-12-01

    Nanotechnology-based tools are beginning to emerge as promising platforms for quantitative high-throughput analysis of live cells and tissues. Despite unprecedented progress made over the last decade, a challenge still lies in integrating emerging nanotechnology-based tools into macroscopic biomedical apparatuses for practical purposes in biomedical sciences. In this review, we discuss the recent advances and limitations in the analysis and control of mechanical, biochemical, fluidic, and optical interactions in the interface areas of nanotechnologybased materials and living cells in both in vitro and in vivo settings.

  17. Clinico-biochemical correlation to histological findings in alcoholic liver disease: a single centre study from eastern India.

    PubMed

    Ray, Sayantan; Khanra, Dibbendhu; Sonthalia, Nikhil; Kundu, Supratip; Biswas, Kaushik; Talukdar, Arunansu; Saha, Manjari; Bera, Himel

    2014-10-01

    Alcoholism is a health problem not only in developed countries but also in developing countries. Cirrhosis due to alcohol is a common cause of death among individuals abusing alcohol. A better knowledge of the spectrum of alcoholic liver diseases, its clinical, biochemical and histopathological features could result in early detection and prevention of alcoholic liver diseases before it's catastrophic and life threatening effects. A total of 200 patients with alcoholic liver diseases were studied with respect to alcohol consumption, clinical features, biochemical and histopathological changes. The clinical features, biochemical parameters, and histopathology of liver including Ishak's modified histological activity index (HAI) were correlated with the amount and duration of alcohol consumed. Majority of the patients were in the age group of 40-49 years and all the cases were males. Majority consumed alcohol of about 75-90 grams per day for a duration of 10-12 years. Anorexia and jaundice were the most common symptom and clinical finding respectively. Hyperbilirubinemia and hypoalbuminemia were the most common abnormalities observed in liver function tests. Advanced HAI stages with features of cirrhosis were most frequent histo-pathological finding noted in this study. Clinico-biochemical profile was significantly correlated with degree of alcohol ingestion as well as with liver histopathology. The wide prevalence of alcoholic liver disease including cirrhosis among Indian males was noted with significantly lower quantity and duration of alcohol ingestion. The severity of liver damage is directly proportional to the quantity and duration of alcohol consumed. Clinical features and biochemical changes may forecast the liver histopathology among the patients of alcoholic liver disease.

  18. A 3D puzzle approach to building protein-DNA structures.

    PubMed

    Hinton, Deborah M

    2017-03-15

    Despite recent advances in structural analysis, it is still challenging to obtain a high-resolution structure for a complex of RNA polymerase, transcriptional factors, and DNA. However, using biochemical constraints, 3D printed models of available structures, and computer modeling, one can build biologically relevant models of such supramolecular complexes.

  19. The Curriculum Prerequisite Network: Modeling the Curriculum as a Complex System

    ERIC Educational Resources Information Center

    Aldrich, Preston R.

    2015-01-01

    This article advances the prerequisite network as a means to visualize the hidden structure in an academic curriculum. Networks have been used to represent a variety of complex systems ranging from social systems to biochemical pathways and protein interactions. Here, I treat the academic curriculum as a complex system with nodes representing…

  20. Advances in lanthanide-based luminescent peptide probes for monitoring the activity of kinase and phosphatase.

    PubMed

    Pazos, Elena; Vázquez, M Eugenio

    2014-02-01

    Signaling pathways based on protein phosphorylation and dephosphorylation play critical roles in the orchestration of complex biochemical events and form the core of most signaling pathways in cells (i.e. cell cycle regulation, cell motility, apoptosis, etc.). The understanding of these complex signaling networks is based largely on the biochemical study of their components, i.e. kinases and phosphatases. The development of luminescent sensors for monitoring kinase and phosphatase activity is therefore an active field of research. Examples in the literature usually rely on the modulation of the fluorescence emission of organic fluorophores. However, given the exceptional photophysical properties of lanthanide ions, there is an increased interest in their application as emissive species for monitoring kinase and phosphatase activity. This review summarizes the advances in the development of lanthanide-based luminescent peptide sensors as tools for the study of kinases and phosphatases and provides a critical description of current examples and synthetic approaches to understand these lanthanide-based luminescent peptide sensors. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Biophysical stimulation for in vitro engineering of functional cardiac tissues.

    PubMed

    Korolj, Anastasia; Wang, Erika Yan; Civitarese, Robert A; Radisic, Milica

    2017-07-01

    Engineering functional cardiac tissues remains an ongoing significant challenge due to the complexity of the native environment. However, our growing understanding of key parameters of the in vivo cardiac microenvironment and our ability to replicate those parameters in vitro are resulting in the development of increasingly sophisticated models of engineered cardiac tissues (ECT). This review examines some of the most relevant parameters that may be applied in culture leading to higher fidelity cardiac tissue models. These include the biochemical composition of culture media and cardiac lineage specification, co-culture conditions, electrical and mechanical stimulation, and the application of hydrogels, various biomaterials, and scaffolds. The review will also summarize some of the recent functional human tissue models that have been developed for in vivo and in vitro applications. Ultimately, the creation of sophisticated ECT that replicate native structure and function will be instrumental in advancing cell-based therapeutics and in providing advanced models for drug discovery and testing. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  2. Metal Removal Efficiency And Ecotoxicological Assessment Of Field-Scale Passive Treatment Biochemical Reactors

    EPA Science Inventory

    Anaerobic biochemical reactors (BCRs) are useful for removing metals from mining-impacted water at remote sites. Removal processes include sorption and precipitation of metal sulfides, carbonates, and hydroxides. A question of interest is whether BCRs remove aquatic toxicity. ...

  3. Analysis of deoxyribonucleotide pools in human cancer cell lines using a liquid chromatography coupled with tandem mass spectrometry technique

    PubMed Central

    Zhang, Wei; Tan, Shenglan; Paintsil, Elijah; Dutschman, Ginger E.; Gullen, Elizabeth A.; Chu, Edward; Cheng, Yung-Chi

    2011-01-01

    Endogenous ribonucleotides and deoxyribonucleotides play a critical role in cell function, and determination of their levels is of fundamental importance in understanding key cellular processes involved in energy metabolism and molecular and biochemical signaling pathways. In this study, we determined the respective ribonucleotide and deoxyribonucleotide pool sizes in different human cell lines using a simple sample preparation method and LC/MS/MS. This assay was used to determine alterations in deoxyribonucleotide pools in human pancreatic PANC-1 cells in response to hypoxia and to treatment with either hydroxyurea or aphidicolin. The levels of all deoxyribonucleotide metabolites decreased with hypoxia treatment, except for dUMP, which increased by two-fold. This LC/MS/MS assay is simple, fast, and sensitive, and it represents a significant advance over previously published methodologies. PMID:21620803

  4. Regulating DNA Replication in Plants

    PubMed Central

    Sanchez, Maria de la Paz; Costas, Celina; Sequeira-Mendes, Joana; Gutierrez, Crisanto

    2012-01-01

    Chromosomal DNA replication in plants has requirements and constraints similar to those in other eukaryotes. However, some aspects are plant-specific. Studies of DNA replication control in plants, which have unique developmental strategies, can offer unparalleled opportunities of comparing regulatory processes with yeast and, particularly, metazoa to identify common trends and basic rules. In addition to the comparative molecular and biochemical studies, genomic studies in plants that started with Arabidopsis thaliana in the year 2000 have now expanded to several dozens of species. This, together with the applicability of genomic approaches and the availability of a large collection of mutants, underscores the enormous potential to study DNA replication control in a whole developing organism. Recent advances in this field with particular focus on the DNA replication proteins, the nature of replication origins and their epigenetic landscape, and the control of endoreplication will be reviewed. PMID:23209151

  5. A nerve guidance conduit with topographical and biochemical cues: potential application using human neural stem cells

    NASA Astrophysics Data System (ADS)

    Jenkins, Phillip M.; Laughter, Melissa R.; Lee, David J.; Lee, Young M.; Freed, Curt R.; Park, Daewon

    2015-06-01

    Despite major advances in the pathophysiological understanding of peripheral nerve damage, the treatment of nerve injuries still remains an unmet medical need. Nerve guidance conduits present a promising treatment option by providing a growth-permissive environment that 1) promotes neuronal cell survival and axon growth and 2) directs axonal extension. To this end, we designed an electrospun nerve guidance conduit using a blend of polyurea and poly-caprolactone with both biochemical and topographical cues. Biochemical cues were integrated into the conduit by functionalizing the polyurea with RGD to improve cell attachment. Topographical cues that resemble natural nerve tissue were incorporated by introducing intraluminal microchannels aligned with nanofibers. We determined that electrospinning the polymer solution across a two electrode system with dissolvable sucrose fibers produced a polymer conduit with the appropriate biomimetic properties. Human neural stem cells were cultured on the conduit to evaluate its ability to promote neuronal growth and axonal extension. The nerve guidance conduit was shown to enhance cell survival, migration, and guide neurite extension.

  6. How important is thermodynamics for identifying elementary flux modes?

    PubMed Central

    Peres, Sabine; Jolicœur, Mario; Moulin, Cécile

    2017-01-01

    We present a method for computing thermodynamically feasible elementary flux modes (tEFMs) using equilibrium constants without need of internal metabolite concentrations. The method is compared with the method based on a binary distinction between reversible and irreversible reactions. When all reactions are reversible, adding the constraints based on equilibrium constants reduces the number of elementary flux modes (EFMs) by a factor of two. Declaring in advance some reactions as irreversible, based on reliable biochemical expertise, can in general reduce the number of EFMs by a greater factor. But, even in this case, computing tEFMs can rule out some EFMs which are biochemically irrelevant. We applied our method to two published models described with binary distinction: the monosaccharide metabolism and the central carbon metabolism of Chinese hamster ovary cells. The results show that the binary distinction is in good agreement with biochemical observations. Moreover, the suppression of the EFMs that are not consistent with the equilibrium constants appears to be biologically relevant. PMID:28222104

  7. The journey of integrins and partners in a complex interactions landscape studied by super-resolution microscopy and single protein tracking

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

    Rossier, Olivier; Giannone, Grégory; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux

    Cells adjust their adhesive and cytoskeletal organizations according to changes in the biochemical and physical nature of their surroundings. In return, by adhering and generating forces on the extracellular matrix (ECM) cells organize their microenvironment. Integrin-dependent focal adhesions (FAs) are the converging zones integrating biochemical and biomechanical signals arising from the ECM and the actin cytoskeleton. Thus, integrin-mediated adhesion and mechanotransduction, the conversion of mechanical forces into biochemical signals, are involved in critical cellular functions such as migration, proliferation and differentiation, and their deregulation contributes to pathologies including cancer. A challenging problem is to decipher how stochastic protein movements andmore » interactions lead to formation of dynamic architecture such as integrin-dependent adhesive structures. In this review, we will describe recent advances made possible by super-resolution microscopies and single molecule tracking approaches that provided new understanding on the organization and the dynamics of integrins and intracellular regulators at the nanoscale in living cells.« less

  8. The journey of integrins and partners in a complex interactions landscape studied by super-resolution microscopy and single protein tracking.

    PubMed

    Rossier, Olivier; Giannone, Grégory

    2016-04-10

    Cells adjust their adhesive and cytoskeletal organizations according to changes in the biochemical and physical nature of their surroundings. In return, by adhering and generating forces on the extracellular matrix (ECM) cells organize their microenvironment. Integrin-dependent focal adhesions (FAs) are the converging zones integrating biochemical and biomechanical signals arising from the ECM and the actin cytoskeleton. Thus, integrin-mediated adhesion and mechanotransduction, the conversion of mechanical forces into biochemical signals, are involved in critical cellular functions such as migration, proliferation and differentiation, and their deregulation contributes to pathologies including cancer. A challenging problem is to decipher how stochastic protein movements and interactions lead to formation of dynamic architecture such as integrin-dependent adhesive structures. In this review, we will describe recent advances made possible by super-resolution microscopies and single molecule tracking approaches that provided new understanding on the organization and the dynamics of integrins and intracellular regulators at the nanoscale in living cells. Copyright © 2015. Published by Elsevier Inc.

  9. Scalable Parameter Estimation for Genome-Scale Biochemical Reaction Networks

    PubMed Central

    Kaltenbacher, Barbara; Hasenauer, Jan

    2017-01-01

    Mechanistic mathematical modeling of biochemical reaction networks using ordinary differential equation (ODE) models has improved our understanding of small- and medium-scale biological processes. While the same should in principle hold for large- and genome-scale processes, the computational methods for the analysis of ODE models which describe hundreds or thousands of biochemical species and reactions are missing so far. While individual simulations are feasible, the inference of the model parameters from experimental data is computationally too intensive. In this manuscript, we evaluate adjoint sensitivity analysis for parameter estimation in large scale biochemical reaction networks. We present the approach for time-discrete measurement and compare it to state-of-the-art methods used in systems and computational biology. Our comparison reveals a significantly improved computational efficiency and a superior scalability of adjoint sensitivity analysis. The computational complexity is effectively independent of the number of parameters, enabling the analysis of large- and genome-scale models. Our study of a comprehensive kinetic model of ErbB signaling shows that parameter estimation using adjoint sensitivity analysis requires a fraction of the computation time of established methods. The proposed method will facilitate mechanistic modeling of genome-scale cellular processes, as required in the age of omics. PMID:28114351

  10. A Review: Some biological effects of high LET radiations

    NASA Technical Reports Server (NTRS)

    Wiley, A., Jr.

    1972-01-01

    There are qualitative and quantitative differences in the biological damage observed after exposure to high LET radiation as compared to that caused by low LET radiations. This review is concerned with these differences, which are ultimately reflected at the biochemical, cellular and even whole animal levels. In general, high LET radiations seem to produce biochemical damage which is more severe and possibly less repairable. Experimental data for those effects are presented in terms of biochemical RBE's with consideration of both early and late manifestations. An LET independent process by which significant biochemical damage may result from protons, neutrons and negative pion mesons is discussed.

  11. Recent advances and opportunities in proteomic analyses of tumour heterogeneity.

    PubMed

    Bateman, Nicholas W; Conrads, Thomas P

    2018-04-01

    Solid tumour malignancies comprise a highly variable admixture of tumour and non-tumour cellular populations, forming a complex cellular ecosystem and tumour microenvironment. This tumour heterogeneity is not incidental, and is known to correlate with poor patient prognosis for many cancer types. Indeed, non-malignant cell populations, such as vascular endothelial and immune cells, are known to play key roles supporting and, in some cases, driving aggressive tumour biology, and represent targets of emerging therapeutics, such as antiangiogenesis and immune checkpoint inhibitors. The biochemical interplay between these cellular populations and how they contribute to molecular tumour heterogeneity remains enigmatic, particularly from the perspective of the tumour proteome. This review focuses on recent advances in proteomic methods, namely imaging mass spectrometry, single-cell proteomic techniques, and preanalytical sample processing, that are uniquely positioned to enable detailed analysis of discrete cellular populations within tumours to improve our understanding of tumour proteomic heterogeneity. This review further emphasizes the opportunity afforded by the application of these techniques to the analysis of tumour heterogeneity in formalin-fixed paraffin-embedded archival tumour tissues, as these represent an invaluable resource for retrospective analyses that is now routinely accessible, owing to recent technological and methodological advances in tumour tissue proteomics. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  12. Infrared and Raman Microscopy in Cell Biology

    PubMed Central

    Matthäus, Christian; Bird, Benjamin; Miljković, Miloš; Chernenko, Tatyana; Romeo, Melissa; Diem, Max

    2009-01-01

    This chapter presents novel microscopic methods to monitor cell biological processes of live or fixed cells without the use of any dye, stains, or other contrast agent. These methods are based on spectral techniques that detect inherent spectroscopic properties of biochemical constituents of cells, or parts thereof. Two different modalities have been developed for this task. One of them is infrared micro-spectroscopy, in which an average snapshot of a cell’s biochemical composition is collected at a spatial resolution of typically 25 mm. This technique, which is extremely sensitive and can collect such a snapshot in fractions of a second, is particularly suited for studying gross biochemical changes. The other technique, Raman microscopy (also known as Raman micro-spectroscopy), is ideally suited to study variations of cellular composition on the scale of subcellular organelles, since its spatial resolution is as good as that of fluorescence microscopy. Both techniques exhibit the fingerprint sensitivity of vibrational spectroscopy toward biochemical composition, and can be used to follow a variety of cellular processes. PMID:19118679

  13. Biochemical modulation of 5-fluorouracil by methotrexate in patients with advanced gastric carcinoma.

    PubMed

    Pérez, J E; Lacava, J A; Dominguez, M E; Rodriguez, R; Barbieri, M R; Ortiz, E H; Romero Acuña, L A; Langhi, M J; Romero Acuña, J M; Vallejo, C T; Leone, B A; Machiavelli, M R; Romero, A O

    1998-10-01

    A phase II trial was conducted to evaluate the efficacy and toxicity of a modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) (with leucovorin (LV) rescue) as first-line chemotherapy in patients with locally advanced (inoperable) or metastatic gastric carcinoma. From July 1993 through August 1996, 36 patients with advanced gastric carcinoma received a regimen that consisted of: MTX 200 mg/m2 diluted in 250 ml normal saline by intravenous infusion over 20 minutes at hour 0; 5-FU 1,200 mg/m2 intravenous push injection at hour 20. Beginning 24 hours after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 hours for six doses. Cycles were repeated every 15 days. One patient was not assessable for response. Objective regression was observed in 15 of 37 patients (43%; 95% confidence interval, 26%-60%). One patient (3%) achieved complete response and 14 (40%) achieved partial response. No change was recorded in 14 patients (40%) and progressive disease was noted in six patients (17%). The median time to treatment failure was 7 months and the median survival was 12 months. Toxicity was within acceptable limits but one therapy-related death resulting from severe leukopenia occurred. The dose-limiting toxicity was mucositis. Five episodes of grade 3 or 4 stomatitis were observed and caused dosage modifications of MTX and 5-FU. Biochemical modulation of 5-FU by MTX appears as an attractive modality in patients with advanced gastric cancer. Further investigation both in experimental and clinical fields is needed to clearly define its role and to design the best modulatory strategy.

  14. Challenges and Advances for Genetic Engineering of Non-model Bacteria and Uses in Consolidated Bioprocessing

    PubMed Central

    Yan, Qiang; Fong, Stephen S.

    2017-01-01

    Metabolic diversity in microorganisms can provide the basis for creating novel biochemical products. However, most metabolic engineering projects utilize a handful of established model organisms and thus, a challenge for harnessing the potential of novel microbial functions is the ability to either heterologously express novel genes or directly utilize non-model organisms. Genetic manipulation of non-model microorganisms is still challenging due to organism-specific nuances that hinder universal molecular genetic tools and translatable knowledge of intracellular biochemical pathways and regulatory mechanisms. However, in the past several years, unprecedented progress has been made in synthetic biology, molecular genetics tools development, applications of omics data techniques, and computational tools that can aid in developing non-model hosts in a systematic manner. In this review, we focus on concerns and approaches related to working with non-model microorganisms including developing molecular genetics tools such as shuttle vectors, selectable markers, and expression systems. In addition, we will discuss: (1) current techniques in controlling gene expression (transcriptional/translational level), (2) advances in site-specific genome engineering tools [homologous recombination (HR) and clustered regularly interspaced short palindromic repeats (CRISPR)], and (3) advances in genome-scale metabolic models (GSMMs) in guiding design of non-model species. Application of these principles to metabolic engineering strategies for consolidated bioprocessing (CBP) will be discussed along with some brief comments on foreseeable future prospects. PMID:29123506

  15. Comparative life cycle assessment of lignocellulosic ethanol production: biochemical versus thermochemical conversion.

    PubMed

    Mu, Dongyan; Seager, Thomas; Rao, P Suresh; Zhao, Fu

    2010-10-01

    Lignocellulosic biomass can be converted into ethanol through either biochemical or thermochemical conversion processes. Biochemical conversion involves hydrolysis and fermentation while thermochemical conversion involves gasification and catalytic synthesis. Even though these routes produce comparable amounts of ethanol and have similar energy efficiency at the plant level, little is known about their relative environmental performance from a life cycle perspective. Especially, the indirect impacts, i.e. emissions and resource consumption associated with the production of various process inputs, are largely neglected in previous studies. This article compiles material and energy flow data from process simulation models to develop life cycle inventory and compares the fossil fuel consumption, greenhouse gas emissions, and water consumption of both biomass-to-ethanol production processes. The results are presented in terms of contributions from feedstock, direct, indirect, and co-product credits for four representative biomass feedstocks i.e., wood chips, corn stover, waste paper, and wheat straw. To explore the potentials of the two conversion pathways, different technological scenarios are modeled, including current, 2012 and 2020 technology targets, as well as different production/co-production configurations. The modeling results suggest that biochemical conversion has slightly better performance on greenhouse gas emission and fossil fuel consumption, but that thermochemical conversion has significantly less direct, indirect, and life cycle water consumption. Also, if the thermochemical plant operates as a biorefinery with mixed alcohol co-products separated for chemicals, it has the potential to achieve better performance than biochemical pathway across all environmental impact categories considered due to higher co-product credits associated with chemicals being displaced. The results from this work serve as a starting point for developing full life cycle assessment model that facilitates effective decision-making regarding lignocellulosic ethanol production.

  16. Comparative Life Cycle Assessment of Lignocellulosic Ethanol Production: Biochemical Versus Thermochemical Conversion

    NASA Astrophysics Data System (ADS)

    Mu, Dongyan; Seager, Thomas; Rao, P. Suresh; Zhao, Fu

    2010-10-01

    Lignocellulosic biomass can be converted into ethanol through either biochemical or thermochemical conversion processes. Biochemical conversion involves hydrolysis and fermentation while thermochemical conversion involves gasification and catalytic synthesis. Even though these routes produce comparable amounts of ethanol and have similar energy efficiency at the plant level, little is known about their relative environmental performance from a life cycle perspective. Especially, the indirect impacts, i.e. emissions and resource consumption associated with the production of various process inputs, are largely neglected in previous studies. This article compiles material and energy flow data from process simulation models to develop life cycle inventory and compares the fossil fuel consumption, greenhouse gas emissions, and water consumption of both biomass-to-ethanol production processes. The results are presented in terms of contributions from feedstock, direct, indirect, and co-product credits for four representative biomass feedstocks i.e., wood chips, corn stover, waste paper, and wheat straw. To explore the potentials of the two conversion pathways, different technological scenarios are modeled, including current, 2012 and 2020 technology targets, as well as different production/co-production configurations. The modeling results suggest that biochemical conversion has slightly better performance on greenhouse gas emission and fossil fuel consumption, but that thermochemical conversion has significantly less direct, indirect, and life cycle water consumption. Also, if the thermochemical plant operates as a biorefinery with mixed alcohol co-products separated for chemicals, it has the potential to achieve better performance than biochemical pathway across all environmental impact categories considered due to higher co-product credits associated with chemicals being displaced. The results from this work serve as a starting point for developing full life cycle assessment model that facilitates effective decision-making regarding lignocellulosic ethanol production.

  17. Potential of FTIR spectroscopy for analysis of tears for diagnosis purposes.

    PubMed

    Travo, Adrian; Paya, Clément; Déléris, Gérard; Colin, Joseph; Mortemousque, Bruno; Forfar, Isabelle

    2014-04-01

    It has been widely reported that the tear film, which is crucially important as a protective barrier of the eye, undergoes biochemical changes as a result of a wide range of ocular pathology. This tends to suggest the possibility of early detection of ocular diseases on the basis of biochemical analysis of tears. However, studies of tears by conventional methods of biomolecular and biochemical analysis are often limited by methodological difficulties. Moreover, such analysis could not be applied in the clinic, where structural and morphological analyses by, mainly, slit-lamp biomicroscopy remains the recommended method. In this study, we assessed, for the first time, the potential of FTIR spectroscopy combined with advanced chemometric processing of spectral data for analysis of raw tears for diagnosis purposes. We first optimized sampling and spectral acquisition (tears collection method, tear sample volume, and preservation of the samples) for accurate spectral measurement. On the basis of the results, we focused our study on the possibility of discriminating tears from normal individuals from those of patients with different ocular pathologies, and showed that the most discriminating spectral range is that corresponding to variations of CH2 and CH3 of lipid aliphatic chains. We also report more subtle discrimination of tears from patients with keratoconus and those from patients with non-specific inflammatory ocular diseases, on the basis of variations in spectral ranges attributed notably to lipid and carbohydrate vibrations. Finally, we also succeeded in distinguishing tears from patients with early-stage and late-stage keratoconus on the basis of spectral features attributed to protein structure. Therefore, this study strongly suggests that FTIR spectral analysis of tears could be developed as a valuable and cost-saving tool for biochemical-based detection of ocular diseases, potentially before the appearance of the first morphological signs of diseases. Combined with supervised modelling methods and with use of a spectral data base acquired for representative patients, such a spectral approach could be a useful addition to current methods of clinical analysis for improvement of patient care.

  18. Biomarkers for Cognitive Impairment in Parkinson Disease

    PubMed Central

    Shi, Min; Huber, Bertrand R.; Zhang, Jing

    2010-01-01

    Cognitive impairment, including dementia, is commonly seen in those afflicted with Parkinson disease (PD), particularly at advanced disease stages. Pathologically, PD with dementia (PD-D) is most often associated with the presence of cortical Lewy bodies, as is the closely related dementia with Lewy bodies (DLB). Both PD-D and DLB are also frequently complicated by the presence of neurofibrillary tangles and amyloid plaques, features most often attributed to Alzheimer disease. Biomarkers are urgently needed to differentiate among these disease processes and predict dementia in PD as well as monitor responses of patients to new therapies. A few clinical assessments, along with structural and functional neuroimaging, have been utilized in the last few years with some success in this area. Additionally, a number of other strategies have been employed to identify biochemical/molecular biomarkers associated with cognitive impairment and dementia in PD, e.g., targeted analysis of candidate proteins known to be important to PD pathogenesis and progression in cerebrospinal fluid or blood. Finally, interesting results are emerging from preliminary studies with unbiased and high throughput genomic, proteomic and metabolomic techniques. The current findings and perspectives of applying these strategies and techniques are reviewed in this article, together with potential areas of advancement. PMID:20522092

  19. A high throughput array microscope for the mechanical characterization of biomaterials

    NASA Astrophysics Data System (ADS)

    Cribb, Jeremy; Osborne, Lukas D.; Hsiao, Joe Ping-Lin; Vicci, Leandra; Meshram, Alok; O'Brien, E. Tim; Spero, Richard Chasen; Taylor, Russell; Superfine, Richard

    2015-02-01

    In the last decade, the emergence of high throughput screening has enabled the development of novel drug therapies and elucidated many complex cellular processes. Concurrently, the mechanobiology community has developed tools and methods to show that the dysregulation of biophysical properties and the biochemical mechanisms controlling those properties contribute significantly to many human diseases. Despite these advances, a complete understanding of the connection between biomechanics and disease will require advances in instrumentation that enable parallelized, high throughput assays capable of probing complex signaling pathways, studying biology in physiologically relevant conditions, and capturing specimen and mechanical heterogeneity. Traditional biophysical instruments are unable to meet this need. To address the challenge of large-scale, parallelized biophysical measurements, we have developed an automated array high-throughput microscope system that utilizes passive microbead diffusion to characterize mechanical properties of biomaterials. The instrument is capable of acquiring data on twelve-channels simultaneously, where each channel in the system can independently drive two-channel fluorescence imaging at up to 50 frames per second. We employ this system to measure the concentration-dependent apparent viscosity of hyaluronan, an essential polymer found in connective tissue and whose expression has been implicated in cancer progression.

  20. Biosynthesis of Polyunsaturated Fatty Acids in Marine Invertebrates: Recent Advances in Molecular Mechanisms

    PubMed Central

    Monroig, Óscar; Tocher, Douglas R.; Navarro, Juan C.

    2013-01-01

    Virtually all polyunsaturated fatty acids (PUFA) originate from primary producers but can be modified by bioconversions as they pass up the food chain in a process termed trophic upgrading. Therefore, although the main primary producers of PUFA in the marine environment are microalgae, higher trophic levels have metabolic pathways that can produce novel and unique PUFA. However, little is known about the pathways of PUFA biosynthesis and metabolism in the levels between primary producers and fish that are largely filled by invertebrates. It has become increasingly apparent that, in addition to trophic upgrading, de novo synthesis of PUFA is possible in some lower animals. The unequivocal identification of PUFA biosynthetic pathways in many invertebrates is complicated by the presence of other organisms within them. These organisms include bacteria and algae with PUFA biosynthesis pathways, and range from intestinal flora to symbiotic relationships that can involve PUFA translocation to host organisms. This emphasizes the importance of studying biosynthetic pathways at a molecular level, and the continual expansion of genomic resources and advances in molecular analysis is facilitating this. The present paper highlights recent research into the molecular and biochemical mechanisms of PUFA biosynthesis in marine invertebrates, particularly focusing on cephalopod molluscs. PMID:24152561

  1. Hitchhiker's guide to multi-dimensional plant pathology.

    PubMed

    Saunders, Diane G O

    2015-02-01

    Filamentous pathogens pose a substantial threat to global food security. One central question in plant pathology is how pathogens cause infection and manage to evade or suppress plant immunity to promote disease. With many technological advances over the past decade, including DNA sequencing technology, an array of new tools has become embedded within the toolbox of next-generation plant pathologists. By employing a multidisciplinary approach plant pathologists can fully leverage these technical advances to answer key questions in plant pathology, aimed at achieving global food security. This review discusses the impact of: cell biology and genetics on progressing our understanding of infection structure formation on the leaf surface; biochemical and molecular analysis to study how pathogens subdue plant immunity and manipulate plant processes through effectors; genomics and DNA sequencing technologies on all areas of plant pathology; and new forms of collaboration on accelerating exploitation of big data. As we embark on the next phase in plant pathology, the integration of systems biology promises to provide a holistic perspective of plant–pathogen interactions from big data and only once we fully appreciate these complexities can we design truly sustainable solutions to preserve our resources.

  2. Engineering and Evolution of Saccharomyces cerevisiae to Produce Biofuels and Chemicals.

    PubMed

    Turner, Timothy L; Kim, Heejin; Kong, In Iok; Liu, Jing-Jing; Zhang, Guo-Chang; Jin, Yong-Su

    To mitigate global climate change caused partly by the use of fossil fuels, the production of fuels and chemicals from renewable biomass has been attempted. The conversion of various sugars from renewable biomass into biofuels by engineered baker's yeast (Saccharomyces cerevisiae) is one major direction which has grown dramatically in recent years. As well as shifting away from fossil fuels, the production of commodity chemicals by engineered S. cerevisiae has also increased significantly. The traditional approaches of biochemical and metabolic engineering to develop economic bioconversion processes in laboratory and industrial settings have been accelerated by rapid advancements in the areas of yeast genomics, synthetic biology, and systems biology. Together, these innovations have resulted in rapid and efficient manipulation of S. cerevisiae to expand fermentable substrates and diversify value-added products. Here, we discuss recent and major advances in rational (relying on prior experimentally-derived knowledge) and combinatorial (relying on high-throughput screening and genomics) approaches to engineer S. cerevisiae for producing ethanol, butanol, 2,3-butanediol, fatty acid ethyl esters, isoprenoids, organic acids, rare sugars, antioxidants, and sugar alcohols from glucose, xylose, cellobiose, galactose, acetate, alginate, mannitol, arabinose, and lactose.

  3. Measurement Frontiers in Molecular Biology

    NASA Astrophysics Data System (ADS)

    Laderman, Stephen

    2009-03-01

    Developments of molecular measurements and manipulations have long enabled forefront research in evolution, genetics, biological development and its dysfunction, and the impact of external factors on the behavior of cells. Measurement remains at the heart of exciting and challenging basic and applied problems in molecular and cell biology. Methods to precisely determine the identity and abundance of particular molecules amongst a complex mixture of similar and dissimilar types require the successful design and integration of multiple steps involving biochemical manipulations, separations, physical probing, and data processing. Accordingly, today's most powerful methods for characterizing life at the molecular level depend on coordinated advances in applied physics, biochemistry, chemistry, computer science, and engineering. This is well illustrated by recent approaches to the measurement of DNA, RNA, proteins, and intact cells. Such successes underlie well founded visions of how molecular biology can further assist in answering compelling scientific questions and in enabling the development of remarkable advances in human health. These visions, in turn, are motivating the interdisciplinary creation of even more comprehensive measurements. As a further and closely related consequence, they are motivating innovations in the conceptual and practical approaches to organizing and visualizing large, complex sets of interrelated experimental results and distilling from those data compelling, informative conclusions.

  4. Prediction of anaerobic biodegradability and bioaccessibility of municipal sludge by coupling sequential extractions with fluorescence spectroscopy: towards ADM1 variables characterization.

    PubMed

    Jimenez, Julie; Gonidec, Estelle; Cacho Rivero, Jesús Andrés; Latrille, Eric; Vedrenne, Fabien; Steyer, Jean-Philippe

    2014-03-01

    Advanced dynamic anaerobic digestion models, such as ADM1, require both detailed organic matter characterisation and intimate knowledge of the involved metabolic pathways. In the current study, a methodology for municipal sludge characterization is investigated to describe two key parameters: biodegradability and bioaccessibility of organic matter. The methodology is based on coupling sequential chemical extractions with 3D fluorescence spectroscopy. The use of increasingly strong solvents reveals different levels of organic matter accessibility and the spectroscopy measurement leads to a detailed characterisation of the organic matter. The results obtained from testing 52 municipal sludge samples (primary, secondary, digested and thermally treated) showed a successful correlation with sludge biodegradability and bioaccessibility. The two parameters, traditionally obtained through the biochemical methane potential (BMP) lab tests, are now obtain in only 5 days compared to the 30-60 days usually required. Experimental data, obtained from two different laboratory scale reactors, were used to validate the ADM1 model. The proposed approach showed a strong application potential for reactor design and advanced control of anaerobic digestion processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Hierarchical thinking in network biology: the unbiased modularization of biochemical networks.

    PubMed

    Papin, Jason A; Reed, Jennifer L; Palsson, Bernhard O

    2004-12-01

    As reconstructed biochemical reaction networks continue to grow in size and scope, there is a growing need to describe the functional modules within them. Such modules facilitate the study of biological processes by deconstructing complex biological networks into conceptually simple entities. The definition of network modules is often based on intuitive reasoning. As an alternative, methods are being developed for defining biochemical network modules in an unbiased fashion. These unbiased network modules are mathematically derived from the structure of the whole network under consideration.

  6. Washington State University Algae Biofuels Research

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

    chen, Shulin; McCormick, Margaret; Sutterlin, Rusty

    The goal of this project was to advance algal technologies for the production of biofuels and biochemicals by establishing the Washington State Algae Alliance, a collaboration partnership among two private companies (Targeted Growth, Inc. (TGI), Inventure Chemicals (Inventure) Inc (now Inventure Renewables Inc) and Washington State University (WSU). This project included three major components. The first one was strain development at TGI by genetically engineering cyanobacteria to yield high levels of lipid and other specialty chemicals. The second component was developing an algal culture system at WSU to produce algal biomass as biofuel feedstock year-round in the northern states ofmore » the United States. This system included two cultivation modes, the first one was a phototrophic process and the second a heterotrophic process. The phototrophic process would be used for algae production in open ponds during warm seasons; the heterotrophic process would be used in cold seasons so that year-round production of algal lipid would be possible. In warm seasons the heterotrophic process would also produce algal seeds to be used in the phototrophic culture process. Selected strains of green algae and cyanobacteria developed by TGI were tested in the system. The third component was downstream algal biomass processing by Inventure that included efficiently harvesting the usable fuel fractions from the algae mass and effectively isolating and separating the usable components into specific fractions, and converting isolated fractions into green chemicals.« less

  7. How Do Structure and Charge Affect Metal-Complex Binding to DNA? An Upper-Division Integrated Laboratory Project Using Cyclic Voltammetry

    ERIC Educational Resources Information Center

    Kulczynska, Agnieszka; Johnson, Reed; Frost, Tony; Margerum, Lawrence D.

    2011-01-01

    An advanced undergraduate laboratory project is described that integrates inorganic, analytical, physical, and biochemical techniques to reveal differences in binding between cationic metal complexes and anionic DNA (herring testes). Students were guided to formulate testable hypotheses based on the title question and a list of different metal…

  8. Biomass for thermochemical conversion: targets and challenges

    PubMed Central

    Tanger, Paul; Field, John L.; Jahn, Courtney E.; DeFoort, Morgan W.; Leach, Jan E.

    2013-01-01

    Bioenergy will be one component of a suite of alternatives to fossil fuels. Effective conversion of biomass to energy will require the careful pairing of advanced conversion technologies with biomass feedstocks optimized for the purpose. Lignocellulosic biomass can be converted to useful energy products via two distinct pathways: enzymatic or thermochemical conversion. The thermochemical pathways are reviewed and potential biotechnology or breeding targets to improve feedstocks for pyrolysis, gasification, and combustion are identified. Biomass traits influencing the effectiveness of the thermochemical process (cell wall composition, mineral and moisture content) differ from those important for enzymatic conversion and so properties are discussed in the language of biologists (biochemical analysis) as well as that of engineers (proximate and ultimate analysis). We discuss the genetic control, potential environmental influence, and consequences of modification of these traits. Improving feedstocks for thermochemical conversion can be accomplished by the optimization of lignin levels, and the reduction of ash and moisture content. We suggest that ultimate analysis and associated properties such as H:C, O:C, and heating value might be more amenable than traditional biochemical analysis to the high-throughput necessary for the phenotyping of large plant populations. Expanding our knowledge of these biomass traits will play a critical role in the utilization of biomass for energy production globally, and add to our understanding of how plants tailor their composition with their environment. PMID:23847629

  9. Teaching Old Dyes New Tricks: Biological Probes Built from Fluoresceins and Rhodamines.

    PubMed

    Lavis, Luke D

    2017-06-20

    Small-molecule fluorophores, such as fluorescein and rhodamine derivatives, are critical tools in modern biochemical and biological research. The field of chemical dyes is old; colored molecules were first discovered in the 1800s, and the fluorescein and rhodamine scaffolds have been known for over a century. Nevertheless, there has been a renaissance in using these dyes to create tools for biochemistry and biology. The application of modern chemistry, biochemistry, molecular genetics, and optical physics to these old structures enables and drives the development of novel, sophisticated fluorescent dyes. This critical review focuses on an important example of chemical biology-the melding of old and new chemical knowledge-leading to useful molecules for advanced biochemical and biological experiments.

  10. MATLAB-Based Teaching Modules in Biochemical Engineering

    ERIC Educational Resources Information Center

    Lee, Kilho; Comolli, Noelle K.; Kelly, William J.; Huang, Zuyi

    2015-01-01

    Mathematical models play an important role in biochemical engineering. For example, the models developed in the field of systems biology have been used to identify drug targets to treat pathogens such as Pseudomonas aeruginosa in biofilms. In addition, competitive binding models for chromatography processes have been developed to predict expanded…

  11. Recent advances in biochemical and molecular diagnostics for the rapid detection of antibiotic-resistant Enterobacteriaceae: a focus on ß-lactam resistance.

    PubMed

    Decousser, Jean-Winoc; Poirel, Laurent; Nordmann, Patrice

    2017-04-01

    The rapid detection of resistance is a challenge for clinical microbiologists who wish to prevent deleterious individual and collective consequences such as (i) delaying efficient antibiotic therapy, which worsens the survival rate of the most severely ill patients, or (ii) delaying the isolation of the carriers of multidrug-resistant bacteria and promoting outbreaks; this last consequence is of special concern, and there are an increasing number of approaches and market-based solutions in response. Areas covered: From simple, cheap biochemical tests to whole-genome sequencing, clinical microbiologists must select the most adequate phenotypic and genotypic tools to promptly detect and confirm β-lactam resistance from cultivated bacteria or from clinical specimens. Here, the authors review the published literature from the last 5 years about the primary technical approaches and commercial laboratory reagents for these purposes, including molecular, biochemical and immune assays. Furthermore, the authors discuss their intrinsic and relative performance, and we challenge their putative clinical impact. Expert commentary: Until the availability of fully automated wet and dry whole genome sequencing solutions, microbiologists should focus on inexpensive biochemical tests for cultured isolates or monomicrobial clinical specimen and on using the expensive molecular PCR-based strategies for the targeted screening of complex biological environments.

  12. Real-time biochemical sensor based on Raman scattering with CMOS contact imaging.

    PubMed

    Muyun Cao; Yuhua Li; Yadid-Pecht, Orly

    2015-08-01

    This work presents a biochemical sensor based on Raman scattering with Complementary metal-oxide-semiconductor (CMOS) contact imaging. This biochemical optical sensor is designed for detecting the concentration of solutions. The system is built with a laser diode, an optical filter, a sample holder and a commercial CMOS sensor. The output of the system is analyzed by an image processing program. The system provides instant measurements with a resolution of 0.2 to 0.4 Mol. This low cost and easy-operated small scale system is useful in chemical, biomedical and environmental labs for quantitative bio-chemical concentration detection with results reported comparable to a highly cost commercial spectrometer.

  13. Cancer cachexia, sarcopenia and biochemical markers in patients with advanced non-small cell lung cancer-chemotherapy toxicity and prognostic value.

    PubMed

    Srdic, Drazena; Plestina, Sanja; Sverko-Peternac, Ana; Nikolac, Nora; Simundic, Ana-Maria; Samarzija, Miroslav

    2016-11-01

    Cancer cachexia and sarcopenia are frequently observed in cancer patients and associated with poor survival. The majority of studies of cancer cachexia and sarcopenia have been done in patients with solid tumors of different origins, and there are currently no good predictors of the benefit of chemotherapy or factors that predict survival in advanced cancer. The purpose of our prospective study was to evaluate prevalence of cachexia and sarcopenia using international consensus definition and criteria for diagnosis in patients with diagnosed advanced non-small cell lung cancer (NSCLC) stage IIIB and IV and their relation to chemotherapy toxicity and survival prediction. A secondary aim was to compare several biochemical markers (CRP, IL-6, protein, and albumin) with time to tumor progression in order to assess prognostic value or to guide a treatment. Between December 2013 and April 2015, the prospective cohort study of 100 Caucasian patients with advanced NSCLC stage IIIB or IV, who were referred consecutively to Department for Respiratory Diseases "Jordanovac," was evaluated. Anthropometric measurements and biochemical data (CRP, albumin, protein, IL-6, haemoglobin) together with body composition measurements (total muscle cross-sectional area, lumbar skeletal muscle index) were obtained for each patient before starting with platinum-doublet therapy. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cutoff point. Toxicity was assessed after cycle 1 of treatment and time-to-tumor progression was determined prospectively. One hundred patients with advanced lung cancer were recruited: 67 were male and median age was 64 years. The median time to disease progression was 187 days. The prevalence of cachexia and sarcopenia in study cohort was 69 and 47 %, respectively. CRP, IL-6, and albumin concentration in cachectic compared to non-cachectic patients demonstrated statistically significant difference (p = 0.020, p = 0.040, p = 0.003). Cachexia and sarcopenia were not found to be predictors of chemotoxicity nor was time to tumor progression. On the contrary, albumin concentration with established cutoff point of 37.5 g/L was clearly proved as the predictive factor of both chemotoxicity (OR (95 % CI) = 0.85; p < 0.001) and survival (HR (95 % CI) = 0.55). Albumin level has been shown to be more important predictive marker of chemotherapy toxicity and survival than cachexia and sarcopenia are. This approach in clinical settings can be used to guide the choice of oncologic treatment.

  14. [Significance of PSMA imaging in prostate cancer].

    PubMed

    Gasch, C; Düwel, C; Kopka, K; Kratochwil, C; Vinsensia, M; Eiber, M; Maurer, T; Haberkorn, U; Hadaschik, B; Giesel, F L

    2017-01-01

    Prostate cancer (PCa) is one of the most common malignancies of men in developed countries. To improve clinical diagnostics of PCa, 68 Ga-PSMA-11 was recently introduced as a new PET tracer. 68 Ga-PSMA-11 is able to specifically bind to the prostate-specific membrane antigen (PSMA), which is upregulated on the surface of prostate cancer cells in most patients. To analyse the current significance of 68 Ga-PSMA-11 PET imaging in prostate cancer in relation to staging of men with initial diagnosis, biochemical recurrence and metastatic disease. Retrospective analysis of current literature (PubMed search) regarding 68 Ga-PSMA-11 PET diagnostics in primary staging, in biochemical recurrence and in metastasized disease. Compared to conventional imaging, 68 Ga-PSMA-11 PET/CT reaches a higher sensitivity with an excellent specificity in the clinical diagnosis of primary staging as well as staging for recurrence and advanced, metastasized disease. In biochemical recurrence, 68 Ga-PSMA-11 PET/CT shows significantly higher detection rates in comparison to choline PET/CT, especially in patients with low PSA values. In the clinical diagnosis of recurrent disease, therapy concepts were changed in more than a quarter of the patients due to the use of 68 Ga-PSMA-11 PET/CT. The significance of staging with 68 Ga-PSMA-11 PET/CT in advanced metastasized patients remains uncertain. Due to the excellent results of 68 Ga-PSMA-11 PET imaging, even in patients with slightly elevated PSA levels, it will continue to play an important role in clinical diagnostics of prostate cancer and, thus, its clinical utilization will become more widely spread.

  15. Data quality in drug discovery: the role of analytical performance in ligand binding assays

    NASA Astrophysics Data System (ADS)

    Wätzig, Hermann; Oltmann-Norden, Imke; Steinicke, Franziska; Alhazmi, Hassan A.; Nachbar, Markus; El-Hady, Deia Abd; Albishri, Hassan M.; Baumann, Knut; Exner, Thomas; Böckler, Frank M.; El Deeb, Sami

    2015-09-01

    Despite its importance and all the considerable efforts made, the progress in drug discovery is limited. One main reason for this is the partly questionable data quality. Models relating biological activity and structures and in silico predictions rely on precisely and accurately measured binding data. However, these data vary so strongly, such that only variations by orders of magnitude are considered as unreliable. This can certainly be improved considering the high analytical performance in pharmaceutical quality control. Thus the principles, properties and performances of biochemical and cell-based assays are revisited and evaluated. In the part of biochemical assays immunoassays, fluorescence assays, surface plasmon resonance, isothermal calorimetry, nuclear magnetic resonance and affinity capillary electrophoresis are discussed in details, in addition radiation-based ligand binding assays, mass spectrometry, atomic force microscopy and microscale thermophoresis are briefly evaluated. In addition, general sources of error, such as solvent, dilution, sample pretreatment and the quality of reagents and reference materials are discussed. Biochemical assays can be optimized to provide good accuracy and precision (e.g. percental relative standard deviation <10 %). Cell-based assays are often considered superior related to the biological significance, however, typically they cannot still be considered as really quantitative, in particular when results are compared over longer periods of time or between laboratories. A very careful choice of assays is therefore recommended. Strategies to further optimize assays are outlined, considering the evaluation and the decrease of the relevant error sources. Analytical performance and data quality are still advancing and will further advance the progress in drug development.

  16. Fast and Precise Emulation of Stochastic Biochemical Reaction Networks With Amplified Thermal Noise in Silicon Chips.

    PubMed

    Kim, Jaewook; Woo, Sung Sik; Sarpeshkar, Rahul

    2018-04-01

    The analysis and simulation of complex interacting biochemical reaction pathways in cells is important in all of systems biology and medicine. Yet, the dynamics of even a modest number of noisy or stochastic coupled biochemical reactions is extremely time consuming to simulate. In large part, this is because of the expensive cost of random number and Poisson process generation and the presence of stiff, coupled, nonlinear differential equations. Here, we demonstrate that we can amplify inherent thermal noise in chips to emulate randomness physically, thus alleviating these costs significantly. Concurrently, molecular flux in thermodynamic biochemical reactions maps to thermodynamic electronic current in a transistor such that stiff nonlinear biochemical differential equations are emulated exactly in compact, digitally programmable, highly parallel analog "cytomorphic" transistor circuits. For even small-scale systems involving just 80 stochastic reactions, our 0.35-μm BiCMOS chips yield a 311× speedup in the simulation time of Gillespie's stochastic algorithm over COPASI, a fast biochemical-reaction software simulator that is widely used in computational biology; they yield a 15 500× speedup over equivalent MATLAB stochastic simulations. The chip emulation results are consistent with these software simulations over a large range of signal-to-noise ratios. Most importantly, our physical emulation of Poisson chemical dynamics does not involve any inherently sequential processes and updates such that, unlike prior exact simulation approaches, they are parallelizable, asynchronous, and enable even more speedup for larger-size networks.

  17. Perspectives in metabolic engineering: understanding cellular regulation towards the control of metabolic routes.

    PubMed

    Zadran, Sohila; Levine, Raphael D

    2013-01-01

    Metabolic engineering seeks to redirect metabolic pathways through the modification of specific biochemical reactions or the introduction of new ones with the use of recombinant technology. Many of the chemicals synthesized via introduction of product-specific enzymes or the reconstruction of entire metabolic pathways into engineered hosts that can sustain production and can synthesize high yields of the desired product as yields of natural product-derived compounds are frequently low, and chemical processes can be both energy and material expensive; current endeavors have focused on using biologically derived processes as alternatives to chemical synthesis. Such economically favorable manufacturing processes pursue goals related to sustainable development and "green chemistry". Metabolic engineering is a multidisciplinary approach, involving chemical engineering, molecular biology, biochemistry, and analytical chemistry. Recent advances in molecular biology, genome-scale models, theoretical understanding, and kinetic modeling has increased interest in using metabolic engineering to redirect metabolic fluxes for industrial and therapeutic purposes. The use of metabolic engineering has increased the productivity of industrially pertinent small molecules, alcohol-based biofuels, and biodiesel. Here, we highlight developments in the practical and theoretical strategies and technologies available for the metabolic engineering of simple systems and address current limitations.

  18. Diverse Applications of Electronic-Nose Technologies in Agriculture and Forestry

    PubMed Central

    Wilson, Alphus D.

    2013-01-01

    Electronic-nose (e-nose) instruments, derived from numerous types of aroma-sensor technologies, have been developed for a diversity of applications in the broad fields of agriculture and forestry. Recent advances in e-nose technologies within the plant sciences, including improvements in gas-sensor designs, innovations in data analysis and pattern-recognition algorithms, and progress in material science and systems integration methods, have led to significant benefits to both industries. Electronic noses have been used in a variety of commercial agricultural-related industries, including the agricultural sectors of agronomy, biochemical processing, botany, cell culture, plant cultivar selections, environmental monitoring, horticulture, pesticide detection, plant physiology and pathology. Applications in forestry include uses in chemotaxonomy, log tracking, wood and paper processing, forest management, forest health protection, and waste management. These aroma-detection applications have improved plant-based product attributes, quality, uniformity, and consistency in ways that have increased the efficiency and effectiveness of production and manufacturing processes. This paper provides a comprehensive review and summary of a broad range of electronic-nose technologies and applications, developed specifically for the agriculture and forestry industries over the past thirty years, which have offered solutions that have greatly improved worldwide agricultural and agroforestry production systems. PMID:23396191

  19. Diverse applications of electronic-nose technologies in agriculture and forestry.

    PubMed

    Wilson, Alphus D

    2013-02-08

    Electronic-nose (e-nose) instruments, derived from numerous types of aroma-sensor technologies, have been developed for a diversity of applications in the broad fields of agriculture and forestry. Recent advances in e-nose technologies within the plant sciences, including improvements in gas-sensor designs, innovations in data analysis and pattern-recognition algorithms, and progress in material science and systems integration methods, have led to significant benefits to both industries. Electronic noses have been used in a variety of commercial agricultural-related industries, including the agricultural sectors of agronomy, biochemical processing, botany, cell culture, plant cultivar selections, environmental monitoring, horticulture, pesticide detection, plant physiology and pathology. Applications in forestry include uses in chemotaxonomy, log tracking, wood and paper processing, forest management, forest health protection, and waste management. These aroma-detection applications have improved plant-based product attributes, quality, uniformity, and consistency in ways that have increased the efficiency and effectiveness of production and manufacturing processes. This paper provides a comprehensive review and summary of a broad range of electronic-nose technologies and applications, developed specifically for the agriculture and forestry industries over the past thirty years, which have offered solutions that have greatly improved worldwide agricultural and agroforestry production systems.

  20. Sordaria macrospora, a model organism to study fungal cellular development.

    PubMed

    Engh, Ines; Nowrousian, Minou; Kück, Ulrich

    2010-12-01

    During the development of multicellular eukaryotes, the processes of cellular growth and organogenesis are tightly coordinated. Since the 1940s, filamentous fungi have served as genetic model organisms to decipher basic mechanisms underlying eukaryotic cell differentiation. Here, we focus on Sordaria macrospora, a homothallic ascomycete and important model organism for developmental biology. During its sexual life cycle, S. macrospora forms three-dimensional fruiting bodies, a complex process involving the formation of different cell types. S. macrospora can be used for genetic, biochemical and cellular experimental approaches since diverse tools, including fluorescence microscopy, a marker recycling system and gene libraries, are available. Moreover, the genome of S. macrospora has been sequenced and allows functional genomics analyses. Over the past years, our group has generated and analysed a number of developmental mutants which has greatly enhanced our fundamental understanding about fungal morphogenesis. In addition, our recent research activities have established a link between developmental proteins and conserved signalling cascades, ultimately leading to a regulatory network controlling differentiation processes in a eukaryotic model organism. This review summarizes the results of our recent findings, thus advancing current knowledge of the general principles and paradigms underpinning eukaryotic cell differentiation and development. Copyright © 2010 Elsevier GmbH. All rights reserved.

  1. Analysis of Lipids and Lipid Rafts in Borrelia.

    PubMed

    Toledo, Alvaro; Huang, Zhen; Benach, Jorge L; London, Erwin

    2018-01-01

    Lipid rafts are membrane microdomains that are involved in cellular processes such as protein trafficking and signaling processes, and which play a fundamental role in membrane fluidity and budding. The lipid composition of the membrane and the biochemical characteristics of the lipids found within rafts define the ability of cells to form microdomains and compartmentalize the membrane. In this chapter, we describe the biophysical, biochemical, and molecular approaches used to define and characterize lipid rafts in the Lyme disease agent, Borrelia burgdorferi.

  2. Visualization of Proton and Electron Transfer Processes of a Biochemical Reaction by μSR

    NASA Astrophysics Data System (ADS)

    Kiyotani, Tamiko; Kobayashi, Masayoshi; Tanaka, Ichiro; Niimura, Nobuo

    For the last several years, we have discussed and conducted experiments toward realization of visualization of electron and proton transfer process in an enzyme reaction using muon. As the first step for exploring the useful application of the μSR for the biological system, which is "μSR in Biology". A first μSR experiment on biochemical reaction was conducted using the complex of a digestive enzyme, a kind of serine-protease and the inhibitor at J-PARC and PSI.

  3. Molecular Mechanisms of Neuroplasticity: An Expanding Universe.

    PubMed

    Gulyaeva, N V

    2017-03-01

    Biochemical processes in synapses and other neuronal compartments underlie neuroplasticity (functional and structural alterations in the brain enabling adaptation to the environment, learning, memory, as well as rehabilitation after brain injury). This basic molecular level of brain plasticity covers numerous specific proteins (enzymes, receptors, structural proteins, etc.) participating in many coordinated and interacting signal and metabolic processes, their modulation forming a molecular basis for brain plasticity. The articles in this issue are focused on different "hot points" in the research area of biochemical mechanisms supporting neuroplasticity.

  4. 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.

  5. The Next Frontier: Quantitative Biochemistry in Living Cells.

    PubMed

    Honigmann, Alf; Nadler, André

    2018-01-09

    Researchers striving to convert biology into an exact science foremost rely on structural biology and biochemical reconstitution approaches to obtain quantitative data. However, cell biological research is moving at an ever-accelerating speed into areas where these approaches lose much of their edge. Intrinsically unstructured proteins and biochemical interaction networks composed of interchangeable, multivalent, and unspecific interactions pose unique challenges to quantitative biology, as do processes that occur in discrete cellular microenvironments. Here we argue that a conceptual change in our way of conducting biochemical experiments is required to take on these new challenges. We propose that reconstitution of cellular processes in vitro should be much more focused on mimicking the cellular environment in vivo, an approach that requires detailed knowledge of the material properties of cellular compartments, essentially requiring a material science of the cell. In a similar vein, we suggest that quantitative biochemical experiments in vitro should be accompanied by corresponding experiments in vivo, as many newly relevant cellular processes are highly context-dependent. In essence, this constitutes a call for chemical biologists to convert their discipline from a proof-of-principle science to an area that could rightfully be called quantitative biochemistry in living cells. In this essay, we discuss novel techniques and experimental strategies with regard to their potential to fulfill such ambitious aims.

  6. [Advances of consolidated bioprocessing based on recombinant strategy].

    PubMed

    Zheng, Zongbao; Zhao, Meina; Chen, Tao; Zhao, Xueming

    2013-10-01

    Lignocellulosic biomass represents an abundant, low-cost and renewable source of potentially fermentable sugars. It is acandidate besides petroleum as feedstock for fuel and chemical production. Recent researches on utilizing lignocellulosicsas feedstock boost development of numerous-promising processes for a variety of fuels and chemicals, such as biodiesel, biohydrogen and ethanol. However, high cost in depolymerization is a primary obstacle preventing the use of lignocellulosic biomass as feedstock. Consolidated bioprocessing (CBP), refers to the bioprocess without any exogenous cellulolyotic enzymes added, converting the lignocellulosic material into biochemicals directly, which could potentially avoid the cost of the dedicated enzyme generation step by incorporating enzyme-generating, biomass-degrading and bioproduct-producing capabilities into a single organism through genetic engineering. There are two CBP strategies, native strategy and recombinant strategy. We mainly introduce the recombinant strategy, including its principle, the two responding styles, the contributions of synthetic biology and metabolic engineering and the future challenges.

  7. Nanotechnology in stem cells research: advances and applications.

    PubMed

    Deb, Kaushik Dilip; Griffith, May; Muinck, Ebo De; Rafat, Mehrdad

    2012-01-01

    Human beings suffer from a myriad of disorders caused by biochemical or biophysical alteration of physiological systems leading to organ failure. For a number of these conditions, stem cells and their enormous reparative potential may be the last hope for restoring function to these failing organ or tissue systems. To harness the potential of stem cells for biotherapeutic applications, we need to work at the size scale of molecules and processes that govern stem cells fate. Nanotechnology provides us with such capacity. Therefore, effective amalgamation of nanotechnology and stem cells - medical nanoscience or nanomedicine - offers immense benefits to the human race. The aim of this paper is to discuss the role and importance of nanotechnology in stem cell research by focusing on several important areas such as stem cell visualization and imaging, genetic modifications and reprogramming by gene delivery systems, creating stem cell niche, and similar therapeutic applications.

  8. Redox-inflammatory synergy in the metabolic syndrome.

    PubMed

    Bryan, Sean; Baregzay, Boran; Spicer, Drew; Singal, Pawan K; Khaper, Neelam

    2013-01-01

    Metabolic syndrome (MetS) comprises interrelated disease states including obesity, insulin resistance and type 2 diabetes (T2DM), dyslipidemia, and hypertension. Essential to normal physiological function, and yet massively damaging in excess, oxidative stress and inflammation are pivotal common threads among the pathologies of MetS. Increasing evidence indicates that redox and inflammatory dysregulation parallels the syndrome's physiological, biochemical, and anthropometric features, leading many to consider the pro-oxidative, pro-inflammatory milieu an unofficial criterion in itself. Left unchecked, cross-promotion of oxidative stress and inflammation creates a feed-forward cycle that can initiate and advance disease progression. Such redox-inflammatory integration is evident in the pathogenesis of obesity, insulin resistance and T2DM, atherogenic dyslipidemia, and hypertension, and is thus hypothesized to be the "common soil" from which they develop. The present review highlights the synergistic contributions of redox-inflammatory processes to each of the components of the MetS.

  9. Metabolon, Inc.

    PubMed

    Ryals, John; Lawton, Kay; Stevens, Daniel; Milburn, Michael

    2007-07-01

    Metabolon is an emerging technology company developing proprietary analytical methods and software for biomarker discovery using metabolomics. The company's aim is to measure all small molecules (<1500 Da) in a biological sample. These small-molecule compounds include biochemicals of cellular metabolism and xenobiotics from diet and environment. Our proprietary mLIMStrade mark system contains advanced metabolomic software and automated data-processing tools that use a variety of data-analysis and quality-control algorithms to convert raw mass-spectrometry data to identified, quantitated compounds. Metabolon's primary focus is a fee-for-service business that exploits this technology for pharmaceutical and biotechnology companies, with additional clients in the consumer goods, cosmetics and agricultural industries. Fee-for-service studies are often collaborations with groups that employ a variety of technologies for biomarker discovery. Metabolon's goal is to develop technology that will automatically analyze any sample for the small-molecule components present and become a standard technology for applications in health and related sciences.

  10. The interactions of peripheral membrane proteins with biological membranes

    DOE PAGES

    Johs, Alexander; Whited, A. M.

    2015-07-29

    The interactions of peripheral proteins with membrane surfaces are critical to many biological processes, including signaling, recognition, membrane trafficking, cell division and cell structure. On a molecular level, peripheral membrane proteins can modulate lipid composition, membrane dynamics and protein-protein interactions. Biochemical and biophysical studies have shown that these interactions are in fact highly complex, dominated by several different types of interactions, and have an interdependent effect on both the protein and membrane. Here we examine three major mechanisms underlying the interactions between peripheral membrane proteins and membranes: electrostatic interactions, hydrophobic interactions, and fatty acid modification of proteins. While experimental approachesmore » continue to provide critical insights into specific interaction mechanisms, emerging bioinformatics resources and tools contribute to a systems-level picture of protein-lipid interactions. Through these recent advances, we begin to understand the pivotal role of protein-lipid interactions underlying complex biological functions at membrane interfaces.« less

  11. Biosynthesis, structural architecture and biotechnological potential of bacterial tannase: a molecular advancement.

    PubMed

    Jana, Arijit; Halder, Suman Kumar; Banerjee, Amrita; Paul, Tanmay; Pati, Bikash Ranjan; Mondal, Keshab Chandra; Das Mohapatra, Pradeep Kumar

    2014-04-01

    Tannin-rich materials are abundantly generated as wastes from several agroindustrial activities. Therefore, tannase is an interesting hydrolase, for bioconversion of tannin-rich materials into value added products by catalyzing the hydrolysis of ester and depside bonds and unlocked a new prospect in different industrial sectors like food, beverages, pharmaceuticals, etc. Microorganisms, particularly bacteria are one of the major sources of tannase. In the last decade, cloning and heterologous expression of novel tannase genes and structural study has gained momentum. In this article, we have emphasized critically on bacterial tannase that have gained worldwide research interest for their diverse properties. The present paper delineate the developments that have taken place in understanding the role of tannase action, microbial sources, various cultivation aspects, downstream processing, salient biochemical properties, structure and active sites, immobilization, efforts in cloning and overexpression and with special emphasis on recent molecular and biotechnological achievements. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. The Hallmarks of Aging

    PubMed Central

    López-Otín, Carlos; Blasco, Maria A.; Partridge, Linda; Serrano, Manuel; Kroemer, Guido

    2013-01-01

    Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contribution to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging with minimal side-effects. PMID:23746838

  13. Gel integration for microfluidic applications.

    PubMed

    Zhang, Xuanqi; Li, Lingjun; Luo, Chunxiong

    2016-05-21

    Molecular diffusive membranes or materials are important for biological applications in microfluidic systems. Hydrogels are typical materials that offer several advantages, such as free diffusion for small molecules, biocompatibility with most cells, temperature sensitivity, relatively low cost, and ease of production. With the development of microfluidic applications, hydrogels can be integrated into microfluidic systems by soft lithography, flow-solid processes or UV cure methods. Due to their special properties, hydrogels are widely used as fluid control modules, biochemical reaction modules or biological application modules in different applications. Although hydrogels have been used in microfluidic systems for more than ten years, many hydrogels' properties and integrated techniques have not been carefully elaborated. Here, we systematically review the physical properties of hydrogels, general methods for gel-microfluidics integration and applications of this field. Advanced topics and the outlook of hydrogel fabrication and applications are also discussed. We hope this review can help researchers choose suitable methods for their applications using hydrogels.

  14. Plant immunity: a lesson from pathogenic bacterial effector proteins.

    PubMed

    Cui, Haitao; Xiang, Tingting; Zhou, Jian-Min

    2009-10-01

    Phytopathogenic bacteria inject an array of effector proteins into host cells to alter host physiology and assist the infection process. Some of these effectors can also trigger disease resistance as a result of recognition in the plant cell by cytoplasmic immune receptors. In addition to effector-triggered immunity, plants immunity can be triggered upon the detection of Pathogen/Microbe-Associated Molecular Patterns by surface-localized immune receptors. Recent progress indicates that many bacterial effector proteins use a variety of biochemical properties to directly attack key components of PAMP-triggered immunity and effector-triggered immunity, providing new insights into the molecular basis of plant innate immunity. Emerging evidence indicate that the evolution of disease resistance in plants is intimately linked to the mechanism by which bacterial effectors promote parasitism. This review focuses on how these studies have conceptually advanced our understanding of plant-pathogen interactions.

  15. Traumatic brain injury: a risk factor for neurodegenerative diseases.

    PubMed

    Gupta, Rajaneesh; Sen, Nilkantha

    2016-01-01

    Traumatic brain injury (TBI), a major global health and socioeconomic problem, is now established as a chronic disease process with a broad spectrum of pathophysiological symptoms followed by long-term disabilities. It triggers multiple and multidirectional biochemical events that lead to neurodegeneration and cognitive impairment. Recent studies have presented strong evidence that patients with TBI history have a tendency to develop proteinopathy, which is the pathophysiological feature of neurodegenerative disorders such as Alzheimer disease (AD), chronic traumatic encephalopathy (CTE), and amyotrophic lateral sclerosis (ALS). This review mainly focuses on mechanisms related to AD, CTE, and ALS that are induced after TBI and their relevance to the advancement of these neurodegenerative diseases. This review encompasses acute effects and chronic neurodegenerative consequences after TBI for a better understanding of TBI-induced neuronal death and to design therapies that will effectively treat patients in the primary or secondary progressive stages.

  16. Investigation on biochemical compositional changes during the microbial fermentation process of Fu brick tea by LC-MS based metabolomics.

    PubMed

    Xu, Jie; Hu, Feng-Lin; Wang, Wei; Wan, Xiao-Chun; Bao, Guan-Hu

    2015-11-01

    Fu brick tea (FBT) is a unique post-fermented tea product which is fermented with fungi during the manufacturing process. In this study, we investigated the biochemical compositional changes occurring during the microbial fermentation process (MFP) of FBT based on non-targeted LC-MS, which was a comprehensive and unbiased methodology. Our data analysis took a two-phase approach: (1) comparison of FBT with other tea products using PCA analysis to exhibit the characteristic effect of MFP on the formation of Fu brick tea and (2) comparison of tea samples throughout the MFP of FBT to elucidate the possible key metabolic pathways produced by the fungi. Non-targeted LC-MS analysis clearly distinguished FBT with other tea samples and highlighted some interesting metabolic pathways during the MFP including B ring fission catechin. Our study demonstrated that those fungi had a significant influence on the biochemical profiles in the FBT and consequently contributed to its unique quality. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Drosophila hematopoiesis under normal conditions and in response to immune stress.

    PubMed

    Letourneau, Manon; Lapraz, Francois; Sharma, Anurag; Vanzo, Nathalie; Waltzer, Lucas; Crozatier, Michèle

    2016-11-01

    The emergence of hematopoietic progenitors and their differentiation into various highly specialized blood cell types constitute a finely tuned process. Unveiling the genetic cascades that control blood cell progenitor fate and understanding how they are modulated in response to environmental changes are two major challenges in the field of hematopoiesis. In the last 20 years, many studies have established important functional analogies between blood cell development in vertebrates and in the fruit fly, Drosophila melanogaster. Thereby, Drosophila has emerged as a powerful genetic model for studying mechanisms that control hematopoiesis during normal development or in pathological situations. Moreover, recent advances in Drosophila have highlighted how intricate cell communication networks and microenvironmental cues regulate blood cell homeostasis. They have also revealed the striking plasticity of Drosophila mature blood cells and the presence of different sites of hematopoiesis in the larva. This review provides an overview of Drosophila hematopoiesis during development and summarizes our current knowledge on the molecular processes controlling larval hematopoiesis, both under normal conditions and in response to an immune challenge, such as wasp parasitism. © 2016 Federation of European Biochemical Societies.

  18. Current advances in mathematical modeling of anti-cancer drug penetration into tumor tissues.

    PubMed

    Kim, Munju; Gillies, Robert J; Rejniak, Katarzyna A

    2013-11-18

    Delivery of anti-cancer drugs to tumor tissues, including their interstitial transport and cellular uptake, is a complex process involving various biochemical, mechanical, and biophysical factors. Mathematical modeling provides a means through which to understand this complexity better, as well as to examine interactions between contributing components in a systematic way via computational simulations and quantitative analyses. In this review, we present the current state of mathematical modeling approaches that address phenomena related to drug delivery. We describe how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules. Finally, we discuss how integration of mathematical modeling with experimental or clinical data can provide better tools to understand the drug delivery process, in particular to examine the specific tissue- or compound-related factors that limit drug penetration through tumors. Such tools will be important in designing new chemotherapy targets and optimal treatment strategies, as well as in developing non-invasive diagnosis to monitor treatment response and detect tumor recurrence.

  19. Computational Biochemistry-Enzyme Mechanisms Explored.

    PubMed

    Culka, Martin; Gisdon, Florian J; Ullmann, G Matthias

    2017-01-01

    Understanding enzyme mechanisms is a major task to achieve in order to comprehend how living cells work. Recent advances in biomolecular research provide huge amount of data on enzyme kinetics and structure. The analysis of diverse experimental results and their combination into an overall picture is, however, often challenging. Microscopic details of the enzymatic processes are often anticipated based on several hints from macroscopic experimental data. Computational biochemistry aims at creation of a computational model of an enzyme in order to explain microscopic details of the catalytic process and reproduce or predict macroscopic experimental findings. Results of such computations are in part complementary to experimental data and provide an explanation of a biochemical process at the microscopic level. In order to evaluate the mechanism of an enzyme, a structural model is constructed which can be analyzed by several theoretical approaches. Several simulation methods can and should be combined to get a reliable picture of the process of interest. Furthermore, abstract models of biological systems can be constructed combining computational and experimental data. In this review, we discuss structural computational models of enzymatic systems. We first discuss various models to simulate enzyme catalysis. Furthermore, we review various approaches how to characterize the enzyme mechanism both qualitatively and quantitatively using different modeling approaches. © 2017 Elsevier Inc. All rights reserved.

  20. Multidimensional biochemical information processing of dynamical patterns

    NASA Astrophysics Data System (ADS)

    Hasegawa, Yoshihiko

    2018-02-01

    Cells receive signaling molecules by receptors and relay information via sensory networks so that they can respond properly depending on the type of signal. Recent studies have shown that cells can extract multidimensional information from dynamical concentration patterns of signaling molecules. We herein study how biochemical systems can process multidimensional information embedded in dynamical patterns. We model the decoding networks by linear response functions, and optimize the functions with the calculus of variations to maximize the mutual information between patterns and output. We find that, when the noise intensity is lower, decoders with different linear response functions, i.e., distinct decoders, can extract much information. However, when the noise intensity is higher, distinct decoders do not provide the maximum amount of information. This indicates that, when transmitting information by dynamical patterns, embedding information in multiple patterns is not optimal when the noise intensity is very large. Furthermore, we explore the biochemical implementations of these decoders using control theory and demonstrate that these decoders can be implemented biochemically through the modification of cascade-type networks, which are prevalent in actual signaling pathways.

  1. Optimal Cytoplasmic Transport in Viral Infections

    PubMed Central

    D'Orsogna, Maria R.; Chou, Tom

    2009-01-01

    For many viruses, the ability to infect eukaryotic cells depends on their transport through the cytoplasm and across the nuclear membrane of the host cell. During this journey, viral contents are biochemically processed into complexes capable of both nuclear penetration and genomic integration. We develop a stochastic model of viral entry that incorporates all relevant aspects of transport, including convection along microtubules, biochemical conversion, degradation, and nuclear entry. Analysis of the nuclear infection probabilities in terms of the transport velocity, degradation, and biochemical conversion rates shows how certain values of key parameters can maximize the nuclear entry probability of the viral material. The existence of such “optimal” infection scenarios depends on the details of the biochemical conversion process and implies potentially counterintuitive effects in viral infection, suggesting new avenues for antiviral treatment. Such optimal parameter values provide a plausible transport-based explanation of the action of restriction factors and of experimentally observed optimal capsid stability. Finally, we propose a new interpretation of how genetic mutations unrelated to the mechanism of drug action may nonetheless confer novel types of overall drug resistance. PMID:20046829

  2. Multidimensional biochemical information processing of dynamical patterns.

    PubMed

    Hasegawa, Yoshihiko

    2018-02-01

    Cells receive signaling molecules by receptors and relay information via sensory networks so that they can respond properly depending on the type of signal. Recent studies have shown that cells can extract multidimensional information from dynamical concentration patterns of signaling molecules. We herein study how biochemical systems can process multidimensional information embedded in dynamical patterns. We model the decoding networks by linear response functions, and optimize the functions with the calculus of variations to maximize the mutual information between patterns and output. We find that, when the noise intensity is lower, decoders with different linear response functions, i.e., distinct decoders, can extract much information. However, when the noise intensity is higher, distinct decoders do not provide the maximum amount of information. This indicates that, when transmitting information by dynamical patterns, embedding information in multiple patterns is not optimal when the noise intensity is very large. Furthermore, we explore the biochemical implementations of these decoders using control theory and demonstrate that these decoders can be implemented biochemically through the modification of cascade-type networks, which are prevalent in actual signaling pathways.

  3. Physiological and molecular biochemical mechanisms of bile formation

    PubMed Central

    Reshetnyak, Vasiliy Ivanovich

    2013-01-01

    This review considers the physiological and molecular biochemical mechanisms of bile formation. The composition of bile and structure of a bile canaliculus, biosynthesis and conjugation of bile acids, bile phospholipids, formation of bile micellar structures, and enterohepatic circulation of bile acids are described. In general, the review focuses on the molecular physiology of the transporting systems of the hepatocyte sinusoidal and apical membranes. Knowledge of physiological and biochemical basis of bile formation has implications for understanding the mechanisms of development of pathological processes, associated with diseases of the liver and biliary tract. PMID:24259965

  4. Origin of Man: Problems in the Interpretation of New Evidence. Test Edition. AAAS Study Guides on Contemporary Problems.

    ERIC Educational Resources Information Center

    Almquist, Alan J.; Cronin, John E.

    This is one of several study guides on contemporary problems produced by the American Association for the Advancement of Science with support of the National Science Foundation. This guide focuses on the origin of man. Part I, The Biochemical Evidence for Human Evolution, contains four sections: (1) Introduction; (2) Macromolecular Data; (3)…

  5. Use of Physiologically Based Pharmacokinetic (PBPK) Models ...

    EPA Pesticide Factsheets

    EPA announced the availability of the final report, Use of Physiologically Based Pharmacokinetic (PBPK) Models to Quantify the Impact of Human Age and Interindividual Differences in Physiology and Biochemistry Pertinent to Risk Final Report for Cooperative Agreement. This report describes and demonstrates techniques necessary to extrapolate and incorporate in vitro derived metabolic rate constants in PBPK models. It also includes two case study examples designed to demonstrate the applicability of such data for health risk assessment and addresses the quantification, extrapolation and interpretation of advanced biochemical information on human interindividual variability of chemical metabolism for risk assessment application. It comprises five chapters; topics and results covered in the first four chapters have been published in the peer reviewed scientific literature. Topics covered include: Data Quality ObjectivesExperimental FrameworkRequired DataTwo example case studies that develop and incorporate in vitro metabolic rate constants in PBPK models designed to quantify human interindividual variability to better direct the choice of uncertainty factors for health risk assessment. This report is intended to serve as a reference document for risk assors to use when quantifying, extrapolating, and interpretating advanced biochemical information about human interindividual variability of chemical metabolism.

  6. Pheochromocytoma-paraganglioma: Biochemical and genetic diagnosis.

    PubMed

    Cano Megías, Marta; Rodriguez Puyol, Diego; Fernández Rodríguez, Loreto; Sención Martinez, Gloria Lisette; Martínez Miguel, Patricia

    Pheochromocytomas and paragangliomas are tumours derived from neural crest cells, which can be diagnosed by biochemical measurement of metanephrine and methoxytyramine. Advances in genetic research have identified many genes involved in the pathogenesis of these tumours, suggesting that up to 35-45% may have an underlying germline mutation. These genes have a singular transcriptional signature and can be grouped into 2 clusters (or groups): cluster 1 (VHL and SHDx), involved in angiogenesis and hypoxia pathways; and cluster 2 (MEN2 and NF1), linked to the kinase signalling pathway. In turn, these genes are associated with a characteristic biochemical phenotype (noradrenergic and adrenergic), and clinical features (location, biological behaviour, age of presentation, etc.) in a large number of cases. Early diagnosis of these tumours, accompanied by a correct genetic diagnosis, should eventually become a priority to enable better treatment, early detection of complications, proper screening of family members and related tumours, as well as an improvement in the overall prognosis of these patients. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  7. Optimal Information Processing in Biochemical Networks

    NASA Astrophysics Data System (ADS)

    Wiggins, Chris

    2012-02-01

    A variety of experimental results over the past decades provide examples of near-optimal information processing in biological networks, including in biochemical and transcriptional regulatory networks. Computing information-theoretic quantities requires first choosing or computing the joint probability distribution describing multiple nodes in such a network --- for example, representing the probability distribution of finding an integer copy number of each of two interacting reactants or gene products while respecting the `intrinsic' small copy number noise constraining information transmission at the scale of the cell. I'll given an overview of some recent analytic and numerical work facilitating calculation of such joint distributions and the associated information, which in turn makes possible numerical optimization of information flow in models of noisy regulatory and biochemical networks. Illustrating cases include quantification of form-function relations, ideal design of regulatory cascades, and response to oscillatory driving.

  8. Organic solvent pretreatment of lignocellulosic biomass for biofuels and biochemicals: A review.

    PubMed

    Zhang, Ke; Pei, Zhijian; Wang, Donghai

    2016-01-01

    Lignocellulosic biomass represents the largest potential volume and lowest cost for biofuel and biochemical production. Pretreatment is an essential component of biomass conversion process, affecting a majority of downstream processes, including enzymatic hydrolysis, fermentation, and final product separation. Organic solvent pretreatment is recognized as an emerging way ahead because of its inherent advantages, such as the ability to fractionate lignocellulosic biomass into cellulose, lignin, and hemicellulose components with high purity, as well as easy solvent recovery and solvent reuse. Objectives of this review were to update and extend previous works on pretreatment of lignocellulosic biomass for biofuels and biochemicals using organic solvents, especially on ethanol, methanol, ethylene glycol, glycerol, acetic acid, and formic acid. Perspectives and recommendations were given to fully describe implementation of proper organic solvent pretreatment for future research. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Catalytic Deoxygenation of Biomass Pyrolysis Vapors to Improve Bio-oil Stability

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

    Dayton, David C.

    2016-12-22

    The President’s Advanced Energy Initiative called for a change in the way Americans fuel their vehicles to promote improved energy security. Increasing biofuels production from domestic lignocellulosic resources requires advanced technology development to achieve the aggressive targets set forth to reduce motor gasoline consumption by 20% in ten years (by 2017). The U.S. Department of Energy (USDOE) Office of the Biomass Program (currently Bioenergy Technologies Office) is actively funding research and development in both biochemical and thermochemical conversion technologies to accelerate the deployment of biofuels technologies in the near future to meet the goals of the Advanced Energy Initiative. Thermochemicalmore » conversion technology options include both gasification and pyrolysis to enable the developing lignocellulosic biorefineries and maximize biomass resource utilization for production of biofuels.« less

  10. Recent advances in mass spectrometry-based proteomics of gastric cancer.

    PubMed

    Kang, Changwon; Lee, Yejin; Lee, J Eugene

    2016-10-07

    The last decade has witnessed remarkable technological advances in mass spectrometry-based proteomics. The development of proteomics techniques has enabled the reliable analysis of complex proteomes, leading to the identification and quantification of thousands of proteins in gastric cancer cells, tissues, and sera. This quantitative information has been used to profile the anomalies in gastric cancer and provide insights into the pathogenic mechanism of the disease. In this review, we mainly focus on the advances in mass spectrometry and quantitative proteomics that were achieved in the last five years and how these up-and-coming technologies are employed to track biochemical changes in gastric cancer cells. We conclude by presenting a perspective on quantitative proteomics and its future applications in the clinic and translational gastric cancer research.

  11. Biochemical and Structural Characterisation of DNA Ligases from Bacteria and Archaea.

    PubMed

    Pergolizzi, Giulia; Wagner, Gerd K; Bowater, Richard Peter

    2016-08-31

    DNA ligases are enzymes that seal breaks in the backbones of DNA, leading to them being essential for the survival of all organisms. DNA ligases have been studied from many different types of cells and organisms and shown to have diverse sizes and sequences, with well conserved specific sequences that are required for enzymatic activity. A significant number of DNA ligases have been isolated or prepared in recombinant forms and, here, we review their biochemical and structural characterisation. All DNA ligases contain an essential lysine that transfers an adenylate group from a co-factor to the 5'-phosphate of the DNA end that will ultimately be joined to the 3'-hydroxyl of the neighbouring DNA strand. The essential DNA ligases in bacteria use nicotinamide adenine dinucleotide ( β -NAD + ) as their co-factor whereas those that are essential in other cells use adenosine-5'-triphosphate (ATP) as their co-factor. This observation suggests that the essential bacterial enzyme could be targeted by novel antibiotics and the complex molecular structure of β -NAD + affords multiple opportunities for chemical modification. Several recent studies have synthesised novel derivatives and their biological activity against a range of DNA ligases has been evaluated as inhibitors for drug discovery and/or non-natural substrates for biochemical applications. Here, we review the recent advances that herald new opportunities to alter the biochemical activities of these important enzymes. The recent development of modified derivatives of nucleotides highlights that the continued combination of structural, biochemical and biophysical techniques will be useful in targeting these essential cellular enzymes. ©2016 The Author(s).

  12. Metabologenomics of Phaeochromocytoma and Paraganglioma: An Integrated Approach for Personalised Biochemical and Genetic Testing

    PubMed Central

    Eisenhofer, Graeme; Klink, Barbara; Richter, Susan; Lenders, Jacques WM; Robledo, Mercedes

    2017-01-01

    The tremendous advances over the past two decades in both clinical genetics and biochemical testing of chromaffin cell tumours have led to new considerations about how these aspects of laboratory medicine can be integrated to improve diagnosis and management of affected patients. With germline mutations in 15 genes now identified to be responsible for over a third of all cases of phaeochromocytomas and paragangliomas, these tumours are recognised to have one of the richest hereditary backgrounds among all neoplasms. Depending on the mutation, tumours show distinct differences in metabolic pathways that relate to or even directly impact clinical presentation. At the same time, there has been improved understanding about how catecholamines are synthesised, stored, secreted and metabolised by chromaffin cell tumours. Although the tumours may not always secrete catecholamines it has become clear that almost all continuously produce and metabolise catecholamines. This has not only fuelled changes in laboratory medicine, but has also assisted in recognition of genotype-biochemical phenotype relationships important for diagnostics and clinical care. In particular, differences in catecholamine and energy pathway metabolomes can guide genetic testing, assist with test interpretation and provide predictions about the nature, behaviour and imaging characteristics of the tumours. Conversely, results of genetic testing are important for guiding how routine biochemical testing should be employed and interpreted in surveillance programmes for at-risk patients. In these ways there are emerging needs for modern laboratory medicine to seamlessly integrate biochemical and genetic testing into the diagnosis and management of patients with chromaffin cell tumours. PMID:29332973

  13. The biochemistry and molecular biology of xenobiotic polymer degradation by microorganisms.

    PubMed

    Kawai, Fusako

    2010-01-01

    Research on microbial degradation of xenobiotic polymers has been underway for more than 40 years. It has exploited a new field not only in applied microbiology but also in environmental microbiology, and has greatly contributed to polymer science by initiating the design of biodegradable polymers. Owing to the development of analytical tools and technology, molecular biological and biochemical advances have made it possible to prospect for degrading microorganisms in the environment and to determine the mechanisms involved in biodegradation when xenobiotic polymers are introduced into the environment and are exposed to microbial attack. In this review, the molecular biological and biochemical aspects of the microbial degradation of xenobiotic polymers are summarized, and possible applications of potent microorganisms, enzymes, and genes in environmental biotechnology are suggested.

  14. Biomacromolecules as carriers in drug delivery and tissue engineering.

    PubMed

    Zhang, Yujie; Sun, Tao; Jiang, Chen

    2018-01-01

    Natural biomacromolecules have attracted increased attention as carriers in biomedicine in recent years because of their inherent biochemical and biophysical properties including renewability, nontoxicity, biocompatibility, biodegradability, long blood circulation time and targeting ability. Recent advances in our understanding of the biological functions of natural-origin biomacromolecules and the progress in the study of biological drug carriers indicate that such carriers may have advantages over synthetic material-based carriers in terms of half-life, stability, safety and ease of manufacture. In this review, we give a brief introduction to the biochemical properties of the widely used biomacromolecule-based carriers such as albumin, lipoproteins and polysaccharides. Then examples from the clinic and in recent laboratory development are summarized. Finally the current challenges and future prospects of present biological carriers are discussed.

  15. Current Advances in the Application of Raman Spectroscopy for Molecular Diagnosis of Cervical Cancer

    PubMed Central

    Ramos, Inês Raquel Martins; Malkin, Alison; Lyng, Fiona Mary

    2015-01-01

    Raman spectroscopy provides a unique biochemical fingerprint capable of identifying and characterizing the structure of molecules, cells, and tissues. In cervical cancer, it is acknowledged as a promising biochemical tool due to its ability to detect premalignancy and early malignancy stages. This review summarizes the key research in the area and the evidence compiled is very encouraging for ongoing and further research. In addition to the diagnostic potential, promising results for HPV detection and monitoring treatment response suggest more than just a diagnosis prospective. A greater body of evidence is however necessary before Raman spectroscopy is fully validated for clinical use and larger comprehensive studies are required to fully establish the role of Raman spectroscopy in the molecular diagnostics of cervical cancer. PMID:26180802

  16. Carbon and nutrient removal from on-site wastewater using extended-aeration activated sludge and ion exchange.

    PubMed

    Safferman, Steven I; Burks, Bennette D; Parker, Robert A

    2004-01-01

    The need to improve on-site wastewater treatment processes is being realized as populations move into more environmentally sensitive regions and regulators adopt the total maximum daily load approach to watershed management. Under many conditions, septic systems do not provide adequate treatment; therefore, advanced systems are required. These systems must remove significant amounts of biochemical oxygen demand (BOD) and suspended solids, and substantially nitrify, denitrify, and remove phosphorus. Many existing advanced on-site wastewater systems effectively remove BOD, suspended solids, and ammonia, but few substantially denitrify and uptake phosphorus. The purpose of this research was to design and test modifications to an existing on-site wastewater treatment system to improve denitrification and phosphorus removal. The Nayadic (Consolidated Treatment Systems, Inc., Franklin, Ohio), an established, commercially available, extended-aeration, activated sludge process, was used to represent a typical existing system. Several modifications were considered based on a literature review, and the option with the best potential was tested. To improve denitrification, a supplemental treatment tank was installed before the Nayadic and a combination flow splitter, sump, and pump box with a recirculation system was installed after it. A recirculation pump returned a high proportion of the system effluent back to the supplemental treatment tank. Two supplemental treatment tank sizes, three flowrates, and three recirculation rates were tested. Actual wastewater was dosed as brief slugs to the system in accordance with a set schedule. Several ion-exchange resins housed in a contact column were tested on the effluent for their potential to remove phosphorus. Low effluent levels of five-day biochemical oxygen demand, suspended solids, and total nitrogen were achieved and substantial phosphorous removal was also achieved using a 3780-L supplemental treatment tank, a recirculation ratio of 5:1, and a fine-grain activated aluminum-oxide-exchange media. Good results were also obtained with an 1890-L supplemental treatment tank and a recirculation ratio of 3:1. The most significant benefit of the supplemental treatment tank, in combination with the recirculation system, appears to be the low nitrogen concentration dosed to the Nayadic. By reducing the nitrogen concentration and spreading out its mass over time during no-flow periods, the Nayadic's inherent low-level denitrifying capacity was more closely matched and effective treatment was achieved.

  17. Biochemical and physiological processes associated with the differential ozone response in ozone-tolerant and sensitive soybean genotypes

    USDA-ARS?s Scientific Manuscript database

    Biochemical and physiological traits of two soybean [Glycine max (L.) Merr.] genotypes that differ in sensitivity to ozone (O3) were investigated to determine the possible basis for the differential response. Fiskeby III (O3-tolerant) and Mandarin (Ottawa) (O3-sensitive) were grown in a greenhouse ...

  18. Acidic deposition, cation mobilization, and biochemical indicators of stress in healthy red spruce

    Treesearch

    Walter C. Shortle; Kevin T. Smith; Rakesh Minocha; Gregory B. Lawrence; Mark B. David

    1997-01-01

    Dendrochemical and biochemical markers link stress in apparently healthy red spruce trees (Picea rubens) to acidic deposition. Acidic deposition to spruce forests of the northeastern USA increased sharply during the 1960s. Previous reports related visible damage of trees at high elevations to root and soil processes. In this report, dendrochemical...

  19. Methods of mesophyll conductance estimation: its impact on key biochemical parameters and photosynthetic limitations in phosphorus-stressed soybean across CO2

    USDA-ARS?s Scientific Manuscript database

    Photosynthetic potential in C3 plants is largely limited by CO2 diffusion through stomata (Ls) and mesophyll (Lm) and photo-biochemical (Lb) processes. Accurate estimation of mesophyll conductance (gm) using gas exchange (GE) and chlorophyll fluorescence (CF) parameters of the photosynthetic proces...

  20. Services provided in support of the planetary quarantine requirements of the National Aeronautics and Space Administration

    NASA Technical Reports Server (NTRS)

    Favero, M. S.

    1972-01-01

    The evaluation is discussed of the terminal sterilization process for unmanned lander spacecraft. Results of biochemical test deviations encountered with the identification schemes are tabulated. Studies to examine the possibility of shifts in biochemical reaction patterns during storage and subculture of the environmental Bacillius isolates are also reported.

  1. Cartilage tissue engineering: recent advances and perspectives from gene regulation/therapy.

    PubMed

    Li, Kuei-Chang; Hu, Yu-Chen

    2015-05-01

    Diseases in articular cartilages affect millions of people. Despite the relatively simple biochemical and cellular composition of articular cartilages, the self-repair ability of cartilage is limited. Successful cartilage tissue engineering requires intricately coordinated interactions between matrerials, cells, biological factors, and phycial/mechanical factors, and still faces a multitude of challenges. This article presents an overview of the cartilage biology, current treatments, recent advances in the materials, biological factors, and cells used in cartilage tissue engineering/regeneration, with strong emphasis on the perspectives of gene regulation (e.g., microRNA) and gene therapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. The Heritage of Radiotracers for PET

    DOE R&D Accomplishments Database

    Fowler, J. S.; Wolf, A. P.

    1988-05-01

    The history of PET research clearly demonstrates that it is advances in chemistry coupled with a detailed examination of the biochemistry of new radiotracers which has allowed the PET method to be applied to new areas of biology and medicine. Radiotracers whose regional distribution reflects glucose metabolism, neutrotransmitter activity and enzyme activity have all required the development of rapid synthetic methods for the radiotracers themselves and the characterization of their biochemical behavior. This article traces some of the advances in the production of labeled precursors and in radiotracer synthesis and evaluation which have shaped the rapidly expanding application of PET to problems in the neurosciences, in cardiology and in oncology.

  3. Enhancement of methane production in mesophilic anaerobic digestion of secondary sewage sludge by advanced thermal hydrolysis pretreatment.

    PubMed

    Abelleira-Pereira, Jose M; Pérez-Elvira, Sara I; Sánchez-Oneto, Jezabel; de la Cruz, Roberto; Portela, Juan R; Nebot, Enrique

    2015-03-15

    Studies on the development and evolution of anaerobic digestion (AD) pretreatments are nowadays becoming widespread, due to the outstanding benefits that these processes could entail in the management of sewage sludge. Production of sewage sludge in wastewater treatment plants (WWTPs) is becoming an extremely important environmental issue. The work presented in this paper is a continuation of our previous studies with the aim of understanding and developing the advanced thermal hydrolysis (ATH) process. ATH is a novel AD pretreatment based on a thermal hydrolysis (TH) process plus hydrogen peroxide (H2O2) addition that takes advantage of a peroxidation/direct steam injection synergistic effect. The main goal of the present research was to compare the performance of TH and ATH, conducted at a wide range of operating conditions, as pretreatments of mesophilic AD with an emphasis on methane production enhancement as a key parameter and its connection with the sludge solubilization. Results showed that both TH and ATH patently improved methane production in subsequent mesophilic BMP (biochemical methane potential) tests in comparison with BMP control tests (raw secondary sewage sludge). Besides other interesting results and discussions, a promising result was obtained since ATH, operated at temperature (115 °C), pretreatment time (5 min) and pressure (1 bar) considerably below those typically used in TH (170 °C, 30 min, 8 bar), managed to enhance the methane production in subsequent mesophilic BMP tests [biodegradability factor (fB) = cumulative CH4production/cumulative CH4production (Control) = 1.51 ± 0.01] to quite similar levels than conventional TH pretreatment [fB = 1.52 ± 0.03]. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Evaluation of Fenton and ozone-based advanced oxidation processes as mature landfill leachate pre-treatments.

    PubMed

    Cortez, Susana; Teixeira, Pilar; Oliveira, Rosário; Mota, Manuel

    2011-03-01

    Fenton treatment (Fe(2+)/H(2)O(2)) and different ozone-based Advanced Oxidation Processes (AOPs) (O(3), O(3)/OH(-) and O(3)/H(2)O(2)) were evaluated as pre-treatment of a mature landfill leachate, in order to improve the biodegradability of its recalcitrant organic matter for subsequent biological treatment. With a two-fold diluted leachate, at optimised experimental conditions (initial pH 3, H(2)O(2) to Fe(2+) molar ratio of 3, Fe(2+) dosage of 4 mmol L(-1), and reaction time of 40 min) Fenton treatment removed about 46% of chemical oxygen demand (COD) and increased the five-day biochemical oxygen demand (BOD(5)) to COD ratio (BOD(5)/COD) from 0.01 to 0.15. The highest removal efficiency and biodegradability was achieved by ozone at higher pH values, solely or combined with H(2)O(2). These results confirm the enhanced production of hydroxyl radical under such conditions. After the application for 60 min of ozone at 5.6 g O(3)h(-1), initial pH 7, and 400 mg L(-1) of hydrogen peroxide, COD removal efficiency was 72% and BOD(5)/COD increased from 0.01 to 0.24. An estimation of the operating costs of the AOPs processes investigated revealed that Fe(2+)/H(2)O(2) was the most economical system (8.2 € m(-3)g(-1) of COD removed) to treat the landfill leachate. This economic study, however, should be treated with caution since it does not consider the initial investment, prices at plant scale, maintenance and labour costs. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. From biofilm ecology to reactors: a focused review.

    PubMed

    Boltz, Joshua P; Smets, Barth F; Rittmann, Bruce E; van Loosdrecht, Mark C M; Morgenroth, Eberhard; Daigger, Glen T

    2017-04-01

    Biofilms are complex biostructures that appear on all surfaces that are regularly in contact with water. They are structurally complex, dynamic systems with attributes of primordial multicellular organisms and multifaceted ecosystems. The presence of biofilms may have a negative impact on the performance of various systems, but they can also be used beneficially for the treatment of water (defined herein as potable water, municipal and industrial wastewater, fresh/brackish/salt water bodies, groundwater) as well as in water stream-based biological resource recovery systems. This review addresses the following three topics: (1) biofilm ecology, (2) biofilm reactor technology and design, and (3) biofilm modeling. In so doing, it addresses the processes occurring in the biofilm, and how these affect and are affected by the broader biofilm system. The symphonic application of a suite of biological methods has led to significant advances in the understanding of biofilm ecology. New metabolic pathways, such as anaerobic ammonium oxidation (anammox) or complete ammonium oxidation (comammox) were first observed in biofilm reactors. The functions, properties, and constituents of the biofilm extracellular polymeric substance matrix are somewhat known, but their exact composition and role in the microbial conversion kinetics and biochemical transformations are still to be resolved. Biofilm grown microorganisms may contribute to increased metabolism of micro-pollutants. Several types of biofilm reactors have been used for water treatment, with current focus on moving bed biofilm reactors, integrated fixed-film activated sludge, membrane-supported biofilm reactors, and granular sludge processes. The control and/or beneficial use of biofilms in membrane processes is advancing. Biofilm models have become essential tools for fundamental biofilm research and biofilm reactor engineering and design. At the same time, the divergence between biofilm modeling and biofilm reactor modeling approaches is recognized.

  6. Biochemical and physicochemical analysis of fish protein isolate recovered from red snapper (Lutjanus sp.) by-product using isoelectric solubilization/precipitation method

    NASA Astrophysics Data System (ADS)

    Pramono, H.; Pujiastuti, D. Y.; Sahidu, A. M.

    2018-04-01

    The effect of acid- and alkali-process on biochemical and physicochemical characteristics of fish protein isolate from red snapper (Lutjanus sp) by-product was evaluated. Protein recovered by alkali process (16.79%) was higher compared to acid process (13.75%). Reduction of lipid content and total volatile basic nitrogen (TVB-N) exhibited in both treatments indicated both process improved fish protein isolate recovered from red snapper by-product. In addition, the increasing of water holding capacity and oil binding capacity were observed. However, high peroxide value of fish protein isolate was showed in both treatment. This finding indicated that acid and alkali process can be used as a useful method to recover proteins from red snapper by-product. Alkali process gave a protein isolate with better overall quality compared to acid process.

  7. A scalable moment-closure approximation for large-scale biochemical reaction networks

    PubMed Central

    Kazeroonian, Atefeh; Theis, Fabian J.; Hasenauer, Jan

    2017-01-01

    Abstract Motivation: Stochastic molecular processes are a leading cause of cell-to-cell variability. Their dynamics are often described by continuous-time discrete-state Markov chains and simulated using stochastic simulation algorithms. As these stochastic simulations are computationally demanding, ordinary differential equation models for the dynamics of the statistical moments have been developed. The number of state variables of these approximating models, however, grows at least quadratically with the number of biochemical species. This limits their application to small- and medium-sized processes. Results: In this article, we present a scalable moment-closure approximation (sMA) for the simulation of statistical moments of large-scale stochastic processes. The sMA exploits the structure of the biochemical reaction network to reduce the covariance matrix. We prove that sMA yields approximating models whose number of state variables depends predominantly on local properties, i.e. the average node degree of the reaction network, instead of the overall network size. The resulting complexity reduction is assessed by studying a range of medium- and large-scale biochemical reaction networks. To evaluate the approximation accuracy and the improvement in computational efficiency, we study models for JAK2/STAT5 signalling and NFκB signalling. Our method is applicable to generic biochemical reaction networks and we provide an implementation, including an SBML interface, which renders the sMA easily accessible. Availability and implementation: The sMA is implemented in the open-source MATLAB toolbox CERENA and is available from https://github.com/CERENADevelopers/CERENA. Contact: jan.hasenauer@helmholtz-muenchen.de or atefeh.kazeroonian@tum.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID:28881983

  8. Diagnosis of Wilson disease in young children: molecular genetic testing and a paradigm shift from the laboratory diagnosis.

    PubMed

    Seo, Jeong Kee

    2012-12-01

    Wilson disease (WD) is an autosomal recessive disorder of copper metabolism that results in accumulation of copper primarily in the liver, brain and cornea. Mutations in the WD gene, ATP7B, cause failure of copper excretion from hepatocyte into bile and a defective synthesis of ceruloplasmin. More than 500 mutations are now recognized, scattered throughout the ATP7B gene. Since WD has protean clinical presentations, awareness of WD in clinical practice is important for the early diagnosis and prevention of accumulated copper toxicity. Molecular genetic testing is playing an increasingly important role in the diagnosis of WD in uncertain cases and family screening. Siblings should be screened for WD once an index case has been diagnosed. Discrimination of heterozygotes from asymptomatic patients is essential to avoid inappropriate lifelong therapy for heterozygotes. Genetic testing, either by haplotype analysis or by mutation analysis, is the only definite solution for differentiating heterozygote carriers from affected asymptomatic patients. Routine genetic testing, because of the multitude of documented mutations, has been thought to be impractical until recently. However, genetic testing is now being more actively applied to the diagnosis of WD, particularly in young children in whom conventional biochemical diagnosis has much limitation and only genetic testing is able to confirm WD. Because advancement of modern biochemical technology now allows more rapid, easier, and less expensive mutation detection, direct DNA sequencing could be actively considered as the primary mode of diagnostic investigation rather than a supplementary test to the conventional biochemical tests. This review will focus on the recent advancement of molecular genetics and genetic diagnosis of WD in very young children on the basis of research data of the Seoul National University Children's Hospital and recent literature.

  9. The Role of Smoking and Gingival Crevicular Fluid Markers on Coronally Advanced Flap Outcomes

    PubMed Central

    Kaval, Başak; Renaud, Diane E.; Scott, David A.; Buduneli, Nurcan

    2015-01-01

    Background This study evaluates possible effects of smoking on the following: 1) biochemical content in gingival crevicular fluid (GCF) samples from sites of gingival recession and saliva; and 2) clinical outcomes of coronally advanced flap (CAF) for root coverage. Methods Eighteen defects in 15 patients were included in each of the smoker and non-smoker groups. Baseline cotinine, basic fibroblast growth factor, vascular endothelial growth factor, platelet-derived growth factor, interleukin (IL)-8, IL-10, IL-12, tumor necrosis factor-α, matrix metalloproteinase (MMP)-8, MMP-9, and plasminogen activator inhibitor-1 levels were determined in GCF and saliva samples. CAF with microsurgery technique was applied. Plaque index, papilla bleeding index, recession depth (RD), recession width (RW), and root surface area were evaluated at baseline and postoperative months 1, 3, and 6. Probing depth, clinical attachment level (CAL), and keratinized gingival width (KGW) was recorded at baseline and month 6. Percentage of root coverage and complete root coverage were calculated at postoperative months 1, 3, and 6. Results All biochemical parameters were similar in the two groups apart from the definite difference in salivary cotinine concentrations (P = 0.000). Compared with the baseline values, RD, RW, CAL, and root surface area decreased, and KGW increased, with no significant difference between the study groups. CAL gain, percentage of root coverage, and complete root-coverage rates were similar in the study groups. Conclusion Similar baseline biochemical data and comparably high success rates of root coverage with CAF in systemically and periodontally healthy smokers versus non-smokers suggest lack of adverse effects of smoking on clinical outcomes. PMID:23725027

  10. Treatment of Ligament Constructs with Exercise-conditioned Serum: A Translational Tissue Engineering Model.

    PubMed

    Lee-Barthel, Ann; Baar, Keith; West, Daniel W D

    2017-06-11

    In vitro experiments are essential to understand biological mechanisms; however, the gap between monolayer tissue culture and human physiology is large, and translation of findings is often poor. Thus, there is ample opportunity for alternative experimental approaches. Here we present an approach in which human cells are isolated from human anterior cruciate ligament tissue remnants, expanded in culture, and used to form engineered ligaments. Exercise alters the biochemical milieu in the blood such that the function of many tissues, organs and bodily processes are improved. In this experiment, ligament construct culture media was supplemented with experimental human serum that has been 'conditioned' by exercise. Thus the intervention is more biologically relevant since an experimental tissue is exposed to the full endogenous biochemical milieu, including binding proteins and adjunct compounds that may be altered in tandem with the activity of an unknown agent of interest. After treatment, engineered ligaments can be analyzed for mechanical function, collagen content, morphology, and cellular biochemistry. Overall, there are four major advantages versus traditional monolayer culture and animal models, of the physiological model of ligament tissue that is presented here. First, ligament constructs are three-dimensional, allowing for mechanical properties (i.e., function) such as ultimate tensile stress, maximal tensile load, and modulus, to be quantified. Second, the enthesis, the interface between boney and sinew elements, can be examined in detail and within functional context. Third, preparing media with post-exercise serum allows for the effects of the exercise-induced biochemical milieu, which is responsible for the wide range of health benefits of exercise, to be investigated in an unbiased manner. Finally, this experimental model advances scientific research in a humane and ethical manner by replacing the use of animals, a core mandate of the National Institutes of Health, the Center for Disease Control, and the Food and Drug Administration.

  11. Treatment of Ligament Constructs with Exercise-conditioned Serum: A Translational Tissue Engineering Model

    PubMed Central

    Lee-Barthel, Ann; Baar, Keith; West, Daniel W. D.

    2017-01-01

    In vitro experiments are essential to understand biological mechanisms; however, the gap between monolayer tissue culture and human physiology is large, and translation of findings is often poor. Thus, there is ample opportunity for alternative experimental approaches. Here we present an approach in which human cells are isolated from human anterior cruciate ligament tissue remnants, expanded in culture, and used to form engineered ligaments. Exercise alters the biochemical milieu in the blood such that the function of many tissues, organs and bodily processes are improved. In this experiment, ligament construct culture media was supplemented with experimental human serum that has been 'conditioned' by exercise. Thus the intervention is more biologically relevant since an experimental tissue is exposed to the full endogenous biochemical milieu, including binding proteins and adjunct compounds that may be altered in tandem with the activity of an unknown agent of interest. After treatment, engineered ligaments can be analyzed for mechanical function, collagen content, morphology, and cellular biochemistry. Overall, there are four major advantages versus traditional monolayer culture and animal models, of the physiological model of ligament tissue that is presented here. First, ligament constructs are three-dimensional, allowing for mechanical properties (i.e., function) such as ultimate tensile stress, maximal tensile load, and modulus, to be quantified. Second, the enthesis, the interface between boney and sinew elements, can be examined in detail and within functional context. Third, preparing media with post-exercise serum allows for the effects of the exercise-induced biochemical milieu, which is responsible for the wide range of health benefits of exercise, to be investigated in an unbiased manner. Finally, this experimental model advances scientific research in a humane and ethical manner by replacing the use of animals, a core mandate of the National Institutes of Health, the Center for Disease Control, and the Food and Drug Administration. PMID:28654031

  12. A Real-Time and Hands-On Research Course in Protein Purification and Characterization: Purification and Crystal Growth of Human Inosine Triphosphate Pyrophosphatase

    ERIC Educational Resources Information Center

    Kreiling, Jodi L.; Brader, Kerry; Kolar, Carol; Borgstahl, Gloria E. O.

    2011-01-01

    A new lecture/laboratory course to offer advanced biochemical training for undergraduate and early graduate students has been developed in the Department of Chemistry at the University of Nebraska at Omaha. This unique course offers students an opportunity to work hands-on with modern instrumentation not normally found in a predominately…

  13. Surrogate biochemical markers: precise measurement for strategic drug and biologics development.

    PubMed

    Lee, J W; Hulse, J D; Colburn, W A

    1995-05-01

    More efficient drug and biologics development is necessary for future success of pharmaceutical and biotechnology companies. One way to achieve this objective is to use rationally selected surrogate markers to improve the early decision-making process. Using typical clinical chemistry methods to measure biochemical markers may not ensure adequate precision and reproducibility. In contrast, using analytical methods that meet good laboratory practices along with rational selection and validation of biochemical markers can give those who use them a competitive advantage over those who do not by providing meaningful data for earlier decision making.

  14. Comparative Testis Tissue Proteomics Using 2-Dye Versus 3-Dye DIGE Analysis.

    PubMed

    Holland, Ashling

    2018-01-01

    Comparative tissue proteomics aims to analyze alterations of the proteome in response to a stimulus. Two-dimensional difference gel electrophoresis (2D-DIGE) is a modified and advanced form of 2D gel electrophoresis. DIGE is a powerful biochemical method that compares two or three protein samples on the same analytical gel, and can be used to establish differentially expressed protein levels between healthy normal and diseased pathological tissue sample groups. Minimal DIGE labeling can be used via a 2-dye system with Cy3 and Cy5 or a 3-dye system with Cy2, Cy3, and Cy5 to fluorescently label samples with CyDye flours pre-electrophoresis. DIGE circumvents gel-to-gel variability by multiplexing samples to a single gel and through the use of a pooled internal standard for normalization. This form of quantitative high-resolution proteomics facilitates the comparative analysis and evaluation of tissue protein compositions. Comparing tissue groups under different conditions is crucially important for advancing the biomedical field by characterization of cellular processes, understanding pathophysiological development and tissue biomarker discovery. This chapter discusses 2D-DIGE as a comparative tissue proteomic technique and describes in detail the experimental steps required for comparative proteomic analysis employing both options of 2-dye and 3-dye DIGE minimal labeling.

  15. Free Energy-Based Virtual Screening and Optimization of RNase H Inhibitors of HIV-1 Reverse Transcriptase.

    PubMed

    Zhang, Baofeng; D'Erasmo, Michael P; Murelli, Ryan P; Gallicchio, Emilio

    2016-09-30

    We report the results of a binding free energy-based virtual screening campaign of a library of 77 α-hydroxytropolone derivatives against the challenging RNase H active site of the reverse transcriptase (RT) enzyme of human immunodeficiency virus-1. Multiple protonation states, rotamer states, and binding modalities of each compound were individually evaluated. The work involved more than 300 individual absolute alchemical binding free energy parallel molecular dynamics calculations and over 1 million CPU hours on national computing clusters and a local campus computational grid. The thermodynamic and structural measures obtained in this work rationalize a series of characteristics of this system useful for guiding future synthetic and biochemical efforts. The free energy model identified key ligand-dependent entropic and conformational reorganization processes difficult to capture using standard docking and scoring approaches. Binding free energy-based optimization of the lead compounds emerging from the virtual screen has yielded four compounds with very favorable binding properties, which will be the subject of further experimental investigations. This work is one of the few reported applications of advanced-binding free energy models to large-scale virtual screening and optimization projects. It further demonstrates that, with suitable algorithms and automation, advanced-binding free energy models can have a useful role in early-stage drug-discovery programs.

  16. Omics markers of the red cell storage lesion and metabolic linkage

    PubMed Central

    D’Alessandro, Angelo; Nemkov, Travis; Reisz, Julie; Dzieciatkowska, Monika; Wither, Matthew J.; Hansen, Kirk C.

    2017-01-01

    The introduction of omics technologies in the field of Transfusion Medicine has significantly advanced our understanding of the red cell storage lesion. While the clinical relevance of such a lesion is still a matter of debate, quantitative and redox proteomics approaches, as well quantitative metabolic flux analysis and metabolic tracing experiments promise to revolutionise our understanding of the role of blood processing strategies, inform the design and testing of novel additives or technologies (such as pathogen reduction), and evaluate the clinical relevance of donor and recipient biological variability with respect to red cell storability and transfusion outcomes. By reviewing existing literature in this rapidly expanding research endeavour, we highlight for the first time a correlation between metabolic markers of the red cell storage age and protein markers of haemolysis. Finally, we introduce the concept of metabolic linkage, i.e. the appreciation of a network of highly correlated small molecule metabolites which results from biochemical constraints of erythrocyte metabolic enzyme activities. For the foreseeable future, red cell studies will advance Transfusion Medicine and haematology by addressing the alteration of metabolic linkage phenotypes in response to stimuli, including, but not limited to, storage additives, enzymopathies (e.g. glucose 6-phosphate dehydrogenase deficiency), hypoxia, sepsis or haemorrhage. PMID:28263171

  17. N-Linked Glycosylation in Archaea: a Structural, Functional, and Genetic Analysis

    PubMed Central

    Ding, Yan; Meyer, Benjamin H.; Albers, Sonja-Verena; Kaminski, Lina; Eichler, Jerry

    2014-01-01

    SUMMARY N-glycosylation of proteins is one of the most prevalent posttranslational modifications in nature. Accordingly, a pathway with shared commonalities is found in all three domains of life. While excellent model systems have been developed for studying N-glycosylation in both Eukarya and Bacteria, an understanding of this process in Archaea was hampered until recently by a lack of effective molecular tools. However, within the last decade, impressive advances in the study of the archaeal version of this important pathway have been made for halophiles, methanogens, and thermoacidophiles, combining glycan structural information obtained by mass spectrometry with bioinformatic, genetic, biochemical, and enzymatic data. These studies reveal both features shared with the eukaryal and bacterial domains and novel archaeon-specific aspects. Unique features of N-glycosylation in Archaea include the presence of unusual dolichol lipid carriers, the use of a variety of linking sugars that connect the glycan to proteins, the presence of novel sugars as glycan constituents, the presence of two very different N-linked glycans attached to the same protein, and the ability to vary the N-glycan composition under different growth conditions. These advances are the focus of this review, with an emphasis on N-glycosylation pathways in Haloferax, Methanococcus, and Sulfolobus. PMID:24847024

  18. Metabolomics, Standards, and Metabolic Modeling for Synthetic Biology in Plants

    PubMed Central

    Hill, Camilla Beate; Czauderna, Tobias; Klapperstück, Matthias; Roessner, Ute; Schreiber, Falk

    2015-01-01

    Life on earth depends on dynamic chemical transformations that enable cellular functions, including electron transfer reactions, as well as synthesis and degradation of biomolecules. Biochemical reactions are coordinated in metabolic pathways that interact in a complex way to allow adequate regulation. Biotechnology, food, biofuel, agricultural, and pharmaceutical industries are highly interested in metabolic engineering as an enabling technology of synthetic biology to exploit cells for the controlled production of metabolites of interest. These approaches have only recently been extended to plants due to their greater metabolic complexity (such as primary and secondary metabolism) and highly compartmentalized cellular structures and functions (including plant-specific organelles) compared with bacteria and other microorganisms. Technological advances in analytical instrumentation in combination with advances in data analysis and modeling have opened up new approaches to engineer plant metabolic pathways and allow the impact of modifications to be predicted more accurately. In this article, we review challenges in the integration and analysis of large-scale metabolic data, present an overview of current bioinformatics methods for the modeling and visualization of metabolic networks, and discuss approaches for interfacing bioinformatics approaches with metabolic models of cellular processes and flux distributions in order to predict phenotypes derived from specific genetic modifications or subjected to different environmental conditions. PMID:26557642

  19. Mechanisms, models and biomarkers in amyotrophic lateral sclerosis

    PubMed Central

    Turner, Martin R.; Bowser, Robert; Bruijn, Lucie; Dupuis, Luc; Ludolph, Albert; Mcgrath, Michael; Manfredi, Giovanni; Maragakis, Nicholas; Miller, Robert G.; Pullman, Seth L.; Rutkove, Seward B.; Shaw, Pamela J.; Shefner, Jeremy; Fischbeck, Kenneth H.

    2014-01-01

    The last 30 years have seen a major advance in the understanding of the clinical and pathological heterogeneity of amyotrophic lateral sclerosis (ALS), and its overlap with frontotemporal dementia. Multiple, seemingly disparate biochemical pathways converge on a common clinical syndrome characterized by progressive loss of upper and lower motor neurons. Pathogenic themes in ALS include excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammation, altered energy metabolism, and most recently RNA mis-processing. The transgenic rodent, overexpressing mutant superoxide dismutase-1, is now only one of several models of ALS pathogenesis. The nematode, fruit fly and zebrafish all offer fresh insight, and the development of induced pluripotent stem cell-derived motor neurons holds promise for the screening of candidate therapeutics. The lack of useful biomarkers in ALS contributes to diagnostic delay, and the inability to stratify patients by prognosis may be an important factor in the failure of therapeutic trials. Biomarkers sensitive to disease activity might lessen reliance on clinical measures and survival as trial endpoints and reduce study length. Emerging proteomic markers of neuronal loss and glial activity in cerebrospinal fluid, a cortical signature derived from advanced structural and functional MRI, and the development of more sensitive measurements of lower motor neuron physiology are leading a new phase of biomarker-driven therapeutic discovery. PMID:23678877

  20. Sports-related concussions: diagnosis, complications, and current management strategies.

    PubMed

    Hobbs, Jonathan G; Young, Jacob S; Bailes, Julian E

    2016-04-01

    Sports-related concussions (SRCs) are traumatic events that affect up to 3.8 million athletes per year. The initial diagnosis and management is often instituted on the field of play by coaches, athletic trainers, and team physicians. SRCs are usually transient episodes of neurological dysfunction following a traumatic impact, with most symptoms resolving in 7-10 days; however, a small percentage of patients will suffer protracted symptoms for years after the event and may develop chronic neurodegenerative disease. Rarely, SRCs are associated with complications, such as skull fractures, epidural or subdural hematomas, and edema requiring neurosurgical evaluation. Current standards of care are based on a paradigm of rest and gradual return to play, with decisions driven by subjective and objective information gleaned from a detailed history and physical examination. Advanced imaging techniques such as functional MRI, and detailed understanding of the complex pathophysiological process underlying SRCs and how they affect the athletes acutely and long-term, may change the way physicians treat athletes who suffer a concussion. It is hoped that these advances will allow a more accurate assessment of when an athlete is truly safe to return to play, decreasing the risk of secondary impact injuries, and provide avenues for therapeutic strategies targeting the complex biochemical cascade that results from a traumatic injury to the brain.

  1. Computer Simulation in Predicting Biochemical Processes and Energy Balance at WWTPs

    NASA Astrophysics Data System (ADS)

    Drewnowski, Jakub; Zaborowska, Ewa; Hernandez De Vega, Carmen

    2018-02-01

    Nowadays, the use of mathematical models and computer simulation allow analysis of many different technological solutions as well as testing various scenarios in a short time and at low financial budget in order to simulate the scenario under typical conditions for the real system and help to find the best solution in design or operation process. The aim of the study was to evaluate different concepts of biochemical processes and energy balance modelling using a simulation platform GPS-x and a comprehensive model Mantis2. The paper presents the example of calibration and validation processes in the biological reactor as well as scenarios showing an influence of operational parameters on the WWTP energy balance. The results of batch tests and full-scale campaign obtained in the former work were used to predict biochemical and operational parameters in a newly developed plant model. The model was extended with sludge treatment devices, including anaerobic digester. Primary sludge removal efficiency was found as a significant factor determining biogas production and further renewable energy production in cogeneration. Water and wastewater utilities, which run and control WWTP, are interested in optimizing the process in order to save environment, their budget and decrease the pollutant emissions to water and air. In this context, computer simulation can be the easiest and very useful tool to improve the efficiency without interfering in the actual process performance.

  2. Metabonomics and medicine: the Biochemical Oracle.

    PubMed

    Mitchell, Steve; Holmes, Elaine; Carmichael, Paul

    2002-10-01

    Occasionally, a new idea emerges that has the potential to revolutionize an entire field of scientific endeavour. It is now within our grasp to be able to detect subtle perturbations within the phenomenally complex biochemical matrix of living organisms. The discipline of metabonomics promises an all-encompassing approach to understanding total, yet fundamental, changes occurring in disease processes, drug toxicity and cell function.

  3. Organization of biogeochemical nitrogen pathways with switch-like adjustment in fluctuating soil redox conditions

    PubMed Central

    Lamba, Sanjay; Bera, Soumen; Rashid, Mubasher; Medvinsky, Alexander B.; Acquisti, Claudia; Li, Bai-Lian

    2017-01-01

    Nitrogen is cycled throughout ecosystems by a suite of biogeochemical processes. The high complexity of the nitrogen cycle resides in an intricate interplay between reversible biochemical pathways alternatively and specifically activated in response to diverse environmental cues. Despite aggressive research, how the fundamental nitrogen biochemical processes are assembled and maintained in fluctuating soil redox conditions remains elusive. Here, we address this question using a kinetic modelling approach coupled with dynamical systems theory and microbial genomics. We show that alternative biochemical pathways play a key role in keeping nitrogen conversion and conservation properties invariant in fluctuating environments. Our results indicate that the biochemical network holds inherent adaptive capacity to stabilize ammonium and nitrate availability, and that the bistability in the formation of ammonium is linked to the transient upregulation of the amo-hao mediated nitrification pathway. The bistability is maintained by a pair of complementary subsystems acting as either source or sink type systems in response to soil redox fluctuations. It is further shown how elevated anthropogenic pressure has the potential to break down the stability of the system, altering substantially ammonium and nitrate availability in the soil, with dramatic effects on biodiversity. PMID:28280580

  4. Functional analysis of H. sapiens DNA polymerase γ spacer mutation W748S with and without common variant E1143G

    PubMed Central

    Palin, Eino JH; Lesonen, Annamari; Farr, Carol L; Euro, Liliya; Suomalainen, Anu; Kaguni, Laurie S

    2010-01-01

    Mitochondrial DNA polymerase, POLG, is the sole DNA polymerase found in animal mitochondria. In humans, POLGα W748S in cis with an E1143G mutation has been linked to a new type of recessive ataxia, MIRAS, which is the most common inherited ataxia in Finland. We investigated the biochemical phenotypes of the W748S amino acid change, using recombinant human POLG. We measured processive and non-processive DNA polymerase activity, DNA binding affinity, enzyme processivity, and subunit interaction with recombinant POLGβ. In addition, we studied the effects of the W748S and E1143G mutations in primary human cell cultures using retroviral transduction. Here, we examined cell viability, mitochondrial DNA copy number, and products of mitochondrial translation. Our results indicate that the W748S mutant POLGα does not exhibit a clear biochemical phenotype, making it indistinguishable from wild type POLGα and as such, fail to replicate previously published results. Furthermore, results from the cell models were concurrent with the findings from patients, and support our biochemical findings. PMID:20153822

  5. Efficient ethanol production from dried oil palm trunk treated by hydrothermolysis and subsequent enzymatic hydrolysis.

    PubMed

    Eom, In-Yong; Yu, Ju-Hyun; Jung, Chan-Duck; Hong, Kyung-Sik

    2015-01-01

    Oil palm trunk (OPT) is a valuable bioresource for the biorefinery industry producing biofuels and biochemicals. It has the distinct feature of containing a large amount of starch, which, unlike cellulose, can be easily solubilized by water when heated and hydrolyzed to glucose by amylolytic enzymes without pretreatment for breaking down the biomass recalcitrance. Therefore, it is suggested as beneficial to extract most of the starch from OPT through autoclaving and subsequent amylolytic hydrolysis prior to pretreatment. However, this treatment requires high capital and operational costs, and there could be a high probability of microbial contamination during starch processing. In terms of biochemical conversion of OPT, this study aimed to develop a simple and efficient ethanol conversion process without any chemical use such as acids and bases or detoxification. For comparison with the proposed efficient ethanol conversion process, OPT was subjected to hydrothermal treatment at 180 °C for 30 min. After enzymatic hydrolysis of PWS, 43.5 g of glucose per 100 g dry biomass was obtained, which corresponds to 81.3 % of the theoretical glucose yield. Through subsequent alcohol fermentation, 81.4 % ethanol yield of the theoretical ethanol yield was achieved. To conduct the proposed new process, starch in OPT was converted to ethanol through enzymatic hydrolysis and subsequent fermentation prior to hydrothermal treatment, and the resulting slurry was subjected to identical processes that were applied to control. Consequently, a high-glucose yield of 96.3 % was achieved, and the resulting ethanol yield was 93.5 %. The proposed new process was a simple method for minimizing the loss of starch during biochemical conversion and maximizing ethanol production as well as fermentable sugars from OPT. In addition, this methodology offers the advantage of reducing operational and capital costs due to minimizing the process for ethanol production by excluding expensive processes related to detoxification prior to enzymatic hydrolysis and fermentation such as washing/conditioning and solid-liquid separation of pretreated slurry. The potential future use of xylose-digestible microorganisms could further increase the ethanol yield from the proposed process, thereby increasing its effectiveness for the conversion of OPT into biofuels and biochemicals.

  6. Advanced Engineering Strategies for Periodontal Complex Regeneration.

    PubMed

    Park, Chan Ho; Kim, Kyoung-Hwa; Lee, Yong-Moo; Seol, Yang-Jo

    2016-01-18

    The regeneration and integration of multiple tissue types is critical for efforts to restore the function of musculoskeletal complex. In particular, the neogenesis of periodontal constructs for systematic tooth-supporting functions is a current challenge due to micron-scaled tissue compartmentalization, oblique/perpendicular orientations of fibrous connective tissues to the tooth root surface and the orchestration of multiple regenerated tissues. Although there have been various biological and biochemical achievements, periodontal tissue regeneration remains limited and unpredictable. The purpose of this paper is to discuss current advanced engineering approaches for periodontal complex formations; computer-designed, customized scaffolding architectures; cell sheet technology-based multi-phasic approaches; and patient-specific constructs using bioresorbable polymeric material and 3-D printing technology for clinical application. The review covers various advanced technologies for periodontal complex regeneration and state-of-the-art therapeutic avenues in periodontal tissue engineering.

  7. Bio-Spectroscopic Imaging Provides Evidence of Hippocampal Zn Deficiency and Decreased Lipid Unsaturation in an Accelerated Ageing Mouse Model.

    PubMed

    Fimognari, Nicholas; Hollings, Ashley; Lam, Virginie; Tidy, Rebecca J; Kewish, Cameron M; Albrecht, Matthew A; Takechi, Ryu; Mamo, John C L; Hackett, Mark J

    2018-06-14

    Western society is facing a health epidemic due to the increasing incidence of dementia in ageing populations, and there are still few effective diagnostic methods, minimal treatment options, and no cure. Ageing is the greatest risk factor for memory loss that occurs during the natural ageing process, as well as being the greatest risk factor for neurodegenerative disease such as Alzheimer's disease. Therefore, greater understanding of the biochemical pathways that drive a healthy ageing brain towards dementia (pathological ageing or Alzheimer's disease), is required to accelerate the development of improved diagnostics and therapies. Unfortunately, many animal models of dementia model chronic amyloid precursor protein over-expression, which although highly relevant to mechanisms of amyloidosis and familial Alzheimer's disease, does not model well dementia during the natural ageing process. A promising animal model reported to model mechanisms of accelerated natural ageing and memory impairments, is the senescence accelerated murine prone strain 8 (SAMP8), which has been adopted by many research group to study the biochemical transitions that occur during brain ageing. A limitation to traditional methods of biochemical characterisation is that many important biochemical and elemental markers (lipid saturation, lactate, transition metals) cannot be imaged at meso- or micro-spatial resolution. Therefore, in this investigation we report the first multi-modal biospectroscopic characterisation of the SAMP8 model, and have identified important biochemical and elemental alterations, and co-localisations, between 4 month old SAMP8 mice and the relevant control (SAMR1) mice. Specifically, we demonstrate direct evidence of altered metabolism and disturbed lipid homeostasis within corpus callosum white matter, in addition to localised hippocampal metal deficiencies, in the accelerated ageing phenotype. Such findings have important implication for future research aimed at elucidating specific biochemical pathways for therapeutic intervention.

  8. Biochemical phenotyping unravels novel metabolic abnormalities and potential biomarkers associated with treatment of GLUT1 deficiency with ketogenic diet.

    PubMed

    Cappuccio, Gerarda; Pinelli, Michele; Alagia, Marianna; Donti, Taraka; Day-Salvatore, Debra-Lynn; Veggiotti, Pierangelo; De Giorgis, Valentina; Lunghi, Simona; Vari, Maria Stella; Striano, Pasquale; Brunetti-Pierri, Nicola; Kennedy, Adam D; Elsea, Sarah H

    2017-01-01

    Global metabolomic profiling offers novel opportunities for the discovery of biomarkers and for the elucidation of pathogenic mechanisms that might lead to the development of novel therapies. GLUT1 deficiency syndrome (GLUT1-DS) is an inborn error of metabolism due to reduced function of glucose transporter type 1. Clinical presentation of GLUT1-DS is heterogeneous and the disorder mirrors patients with epilepsy, movement disorders, or any paroxysmal events or unexplained neurological manifestation triggered by exercise or fasting. The diagnostic biochemical hallmark of the disease is a reduced cerebrospinal fluid (CSF)/blood glucose ratio and the only available treatment is ketogenic diet. This study aimed at advancing our understanding of the biochemical perturbations in GLUT1-DS pathogenesis through biochemical phenotyping and the treatment of GLUT1-DS with a ketogenic diet. Metabolomic analysis of three CSF samples from GLUT1-DS patients not on ketogenic diet was feasible inasmuch as CSF sampling was used for diagnosis before to start with ketogenic diet. The analysis of plasma and urine samples obtained from GLUT1-DS patients treated with a ketogenic diet showed alterations in lipid and amino acid profiles. While subtle, these were consistent findings across the patients with GLUT1-DS on ketogenic diet, suggesting impacts on mitochondrial physiology. Moreover, low levels of free carnitine were present suggesting its consumption in GLUT1-DS on ketogenic diet. 3-hydroxybutyrate, 3-hydroxybutyrylcarnitine, 3-methyladipate, and N-acetylglycine were identified as potential biomarkers of GLUT1-DS on ketogenic diet. This is the first study to identify CSF, plasma, and urine metabolites associated with GLUT1-DS, as well as biochemical changes impacted by a ketogenic diet. Potential biomarkers and metabolic insights deserve further investigation.

  9. Biochemical phenotyping unravels novel metabolic abnormalities and potential biomarkers associated with treatment of GLUT1 deficiency with ketogenic diet

    PubMed Central

    Cappuccio, Gerarda; Pinelli, Michele; Alagia, Marianna; Donti, Taraka; Day-Salvatore, Debra-Lynn; Veggiotti, Pierangelo; De Giorgis, Valentina; Lunghi, Simona; Vari, Maria Stella; Striano, Pasquale; Brunetti-Pierri, Nicola; Kennedy, Adam D.

    2017-01-01

    Global metabolomic profiling offers novel opportunities for the discovery of biomarkers and for the elucidation of pathogenic mechanisms that might lead to the development of novel therapies. GLUT1 deficiency syndrome (GLUT1-DS) is an inborn error of metabolism due to reduced function of glucose transporter type 1. Clinical presentation of GLUT1-DS is heterogeneous and the disorder mirrors patients with epilepsy, movement disorders, or any paroxysmal events or unexplained neurological manifestation triggered by exercise or fasting. The diagnostic biochemical hallmark of the disease is a reduced cerebrospinal fluid (CSF)/blood glucose ratio and the only available treatment is ketogenic diet. This study aimed at advancing our understanding of the biochemical perturbations in GLUT1-DS pathogenesis through biochemical phenotyping and the treatment of GLUT1-DS with a ketogenic diet. Metabolomic analysis of three CSF samples from GLUT1-DS patients not on ketogenic diet was feasible inasmuch as CSF sampling was used for diagnosis before to start with ketogenic diet. The analysis of plasma and urine samples obtained from GLUT1-DS patients treated with a ketogenic diet showed alterations in lipid and amino acid profiles. While subtle, these were consistent findings across the patients with GLUT1-DS on ketogenic diet, suggesting impacts on mitochondrial physiology. Moreover, low levels of free carnitine were present suggesting its consumption in GLUT1-DS on ketogenic diet. 3-hydroxybutyrate, 3-hydroxybutyrylcarnitine, 3-methyladipate, and N-acetylglycine were identified as potential biomarkers of GLUT1-DS on ketogenic diet. This is the first study to identify CSF, plasma, and urine metabolites associated with GLUT1-DS, as well as biochemical changes impacted by a ketogenic diet. Potential biomarkers and metabolic insights deserve further investigation. PMID:28961260

  10. Biochemical Response to Ursodeoxycholic Acid Predicts Survival in a North American Cohort of Primary Biliary Cirrhosis Patients

    PubMed Central

    Lammert, Craig; Juran, Brian D.; Schlicht, Erik; Chan, Landon L.; Atkinson, Elizabeth J.; de Andrade, Mariza; Lazaridis, Konstantinos N.

    2014-01-01

    Background Biochemical response to Ursodeoxycholic Acid among patients with Primary Biliary Cirrhosis remains variable and there is no agreement of an ideal model. Novel assessment of response coupled to histologic progression was recently defined by the Toronto criteria. We retrospectively assessed transplant-free survival and clinical outcomes associated with Ursodeoxycholic Acid response to evaluate the Toronto criteria using a large North American cohort of PBC patients. Methods 398 PBC patients from the Mayo Clinic PBC Genetic Epidemiology (MCPGE) Registry were assessed for Ursodeoxycholic Acid treatment and biochemical response per the Toronto criteria. Responders were defined by reduction in alkaline phosphatase to less than or equal to 1.67 times the upper normal limit by 2 years of treatment, whereas non-responders had alkaline phosphatase values greater than 1.67 times the upper normal limit. Probability of survival was estimated using the Kaplan-Meier method. Results 302 (76%) patients were responders and 96 (24%) were non-responders. Significantly more non-responders developed adverse events related to chronic liver disease compared to responders (Hazard Ratio (HR): 2.77, P = 0.001). Biochemical responders and early-stage disease at treatment start was associated with improved overall transplant-free survival compared to non-responders (HR: 1.9) and patients with late stage disease (HR: 2.7) after age and sex adjustment. Conclusions The Toronto criteria are capable of identifying Ursodeoxycholic Acid-treated Primary Biliary Cirrhosis patients at risk of poor transplant-free survival and adverse clinical outcomes. Our data reveal that despite advanced disease at diagnosis, biochemical response per the Toronto criteria associates with improved overall transplant-free survival. PMID:24317935

  11. Arsenic Uptake, Toxicity, Detoxification, and Speciation in Plants: Physiological, Biochemical, and Molecular Aspects

    PubMed Central

    Abbas, Ghulam; Murtaza, Behzad; Bibi, Irshad; Shahid, Muhammad; Khan, Muhammad Imran; Amjad, Muhammad; Hussain, Munawar; Natasha

    2018-01-01

    Environmental contamination with arsenic (As) is a global environmental, agricultural and health issue due to the highly toxic and carcinogenic nature of As. Exposure of plants to As, even at very low concentration, can cause many morphological, physiological, and biochemical changes. The recent research on As in the soil-plant system indicates that As toxicity to plants varies with its speciation in plants (e.g., arsenite, As(III); arsenate, As(V)), with the type of plant species, and with other soil factors controlling As accumulation in plants. Various plant species have different mechanisms of As(III) or As(V) uptake, toxicity, and detoxification. This review briefly describes the sources and global extent of As contamination and As speciation in soil. We discuss different mechanisms responsible for As(III) and As(V) uptake, toxicity, and detoxification in plants, at physiological, biochemical, and molecular levels. This review highlights the importance of the As-induced generation of reactive oxygen species (ROS), as well as their damaging impacts on plants at biochemical, genetic, and molecular levels. The role of different enzymatic (superoxide dismutase, catalase, glutathione reductase, and ascorbate peroxidase) and non-enzymatic (salicylic acid, proline, phytochelatins, glutathione, nitric oxide, and phosphorous) substances under As(III/V) stress have been delineated via conceptual models showing As translocation and toxicity pathways in plant species. Significantly, this review addresses the current, albeit partially understood, emerging aspects on (i) As-induced physiological, biochemical, and genotoxic mechanisms and responses in plants and (ii) the roles of different molecules in modulation of As-induced toxicities in plants. We also provide insight on some important research gaps that need to be filled to advance our scientific understanding in this area of research on As in soil-plant systems. PMID:29301332

  12. Biochemical response to ursodeoxycholic acid predicts survival in a North American cohort of primary biliary cirrhosis patients.

    PubMed

    Lammert, Craig; Juran, Brian D; Schlicht, Erik; Chan, Landon L; Atkinson, Elizabeth J; de Andrade, Mariza; Lazaridis, Konstantinos N

    2014-10-01

    Biochemical response to ursodeoxycholic acid among patients with primary biliary cirrhosis remains variable, and there is no agreement of an ideal model. Novel assessment of response coupled to histologic progression was recently defined by the Toronto criteria. We retrospectively assessed transplant-free survival and clinical outcomes associated with ursodeoxycholic acid response to evaluate the Toronto criteria using a large North American cohort of PBC patients. Three hundred and ninety-eight PBC patients from the Mayo Clinic PBC Genetic Epidemiology Registry were assessed for ursodeoxycholic acid treatment and biochemical response per the Toronto criteria. Responders were defined by reduction in alkaline phosphatase to less than or equal to 1.67 times the upper normal limit by 2 years of treatment, whereas non-responders had alkaline phosphatase values greater than 1.67 times the upper normal limit. Probability of survival was estimated using the Kaplan-Meier method. Three hundred and two (76 %) patients were responders and 96 (24 %) were non-responders. Significantly more non-responders developed adverse events related to chronic liver disease compared to responders (hazard ratio (HR) 2.77, P = 0.001). Biochemical responders and early-stage disease at treatment start was associated with improved overall transplant-free survival compared to non-responders (HR 1.9) and patients with late-stage disease (HR 2.7) after age and sex adjustment. The Toronto criteria are capable of identifying ursodeoxycholic acid-treated primary biliary cirrhosis patients at risk of poor transplant-free survival and adverse clinical outcomes. Our data reveal that despite advanced disease at diagnosis, biochemical response per the Toronto criteria associates with improved overall transplant-free survival.

  13. Fluid shear stress and tumor metastasis

    PubMed Central

    Huang, Qiong; Hu, Xingbin; He, Wanming; Zhao, Yang; Hao, Shihui; Wu, Qijing; Li, Shaowei; Zhang, Shuyi; Shi, Min

    2018-01-01

    The tumor microenvironment (TME) is a key factor regulating tumor cell invasion and metastasis. The effects of biochemical factors such as stromal cells, immune cells, and cytokines have been previously investigated. Owing to restrictions by the natural barrier between physical and biochemical disciplines, the role of physical factors in tumorigenesis is unclear. However, with the emergence of interdisciplinary mechanobiology and continuous advancements therein in the past 30 years, studies on the effect of physical properties such as hardness or shear stress on tumorigenesis and tumor progression are constantly renewing our understanding of mechanotransduction mechanisms. Shear stress, induced by liquid flow, is known to actively participate in proliferation, apoptosis, invasion, and metastasis of tumor cells. The present review discusses the progress and achievements in studies on tumor fluid microenvironment in recent years, especially fluid shear stress, on tumor metastasis, and presents directions for future study.

  14. Supercolor coding methods for large-scale multiplexing of biochemical assays.

    PubMed

    Rajagopal, Aditya; Scherer, Axel; Homyk, Andrew; Kartalov, Emil

    2013-08-20

    We present a novel method for the encoding and decoding of multiplexed biochemical assays. The method enables a theoretically unlimited number of independent targets to be detected and uniquely identified in any combination in the same sample. For example, the method offers easy access to 12-plex and larger PCR assays, as contrasted to the current 4-plex assays. This advancement would allow for large panels of tests to be run simultaneously in the same sample, saving reagents, time, consumables, and manual labor, while also avoiding the traditional loss of sensitivity due to sample aliquoting. Thus, the presented method is a major technological breakthrough with far-reaching impact on biotechnology, biomedical science, and clinical diagnostics. Herein, we present the mathematical theory behind the method as well as its experimental proof of principle using Taqman PCR on sequences specific to infectious diseases.

  15. Stability of Intercellular Exchange of Biochemical Substances Affected by Variability of Environmental Parameters

    NASA Astrophysics Data System (ADS)

    Mihailović, Dragutin T.; Budinčević, Mirko; Balaž, Igor; Mihailović, Anja

    Communication between cells is realized by exchange of biochemical substances. Due to internal organization of living systems and variability of external parameters, the exchange is heavily influenced by perturbations of various parameters at almost all stages of the process. Since communication is one of essential processes for functioning of living systems it is of interest to investigate conditions for its stability. Using previously developed simplified model of bacterial communication in a form of coupled difference logistic equations we investigate stability of exchange of signaling molecules under variability of internal and external parameters.

  16. Method and apparatus for energy efficient self-aeration in chemical, biochemical, and wastewater treatment processes

    DOEpatents

    Gao, Johnway [Richland, WA; Skeen, Rodney S [Pendleton, OR

    2002-05-28

    The present invention is a pulse spilling self-aerator (PSSA) that has the potential to greatly lower the installation, operation, and maintenance cost associated with aerating and mixing aqueous solutions. Currently, large quantities of low-pressure air are required in aeration systems to support many biochemical production processes and wastewater treatment plants. Oxygen is traditionally supplied and mixed by a compressor or blower and a mechanical agitator. These systems have high-energy requirements and high installation and maintenance costs. The PSSA provides a mixing and aeration capability that can increase operational efficiency and reduce overall cost.

  17. 40 CFR 405.41 - Specialized definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Butter Subcategory § 405.41 Specialized... term “BOD5 input” shall mean the biochemical oxygen demand of the materials entered into process. It...

  18. Removal of herbicidal ionic liquids by electrochemical advanced oxidation processes combined with biological treatment.

    PubMed

    Pęziak-Kowalska, Daria; Fourcade, Florence; Niemczak, Michał; Amrane, Abdeltif; Chrzanowski, Łukasz; Lota, Grzegorz

    2017-05-01

    Recently a new group of ionic liquids (ILs) with herbicidal properties has been proposed for use in agriculture. Owing to the design of specific physicochemical properties, this group, referred to as herbicidal ionic liquids (HILs), allows for reducing herbicide field doses. Several ILs comprising phenoxy herbicides as anions and quaternary ammonium cations have been synthesized and tested under greenhouse and field conditions. However, since they are to be introduced into the environment, appropriate treatment technologies should be developed in order to ensure their proper removal and avoid possible contamination. In this study, didecyldimethylammonium (4-chloro-2-methylphenoxy) acetate was selected as a model HIL to evaluate the efficiency of a hybrid treatment method. Electrochemical oxidation or electro-Fenton was considered as a pretreatment step, whereas biodegradation was selected as the secondary treatment method. Both processes were carried out in current mode, at 10 mA with carbon felt as working electrode. The efficiency of degradation, oxidation and mineralization was evaluated after 6 h. Both processes decreased the total organic carbon and chemical oxygen demand (COD) values and increased the biochemical oxygen demand (BOD 5 ) on the COD ratio to a value close to 0.4, showing that the electrolyzed solutions can be considered as 'readily biodegradable.'

  19. Organogenic nodule formation in hop: a tool to study morphogenesis in plants with biotechnological and medicinal applications.

    PubMed

    Fortes, Ana M; Santos, Filipa; Pais, Maria S

    2010-01-01

    The usage of Humulus lupulus for brewing increased the demand for high-quality plant material. Simultaneously, hop has been used in traditional medicine and recently recognized with anticancer and anti-infective properties. Tissue culture techniques have been reported for a wide range of species, and open the prospect for propagation of disease-free, genetically uniform and massive amounts of plants in vitro. Moreover, the development of large-scale culture methods using bioreactors enables the industrial production of secondary metabolites. Reliable and efficient tissue culture protocol for shoot regeneration through organogenic nodule formation was established for hop. The present review describes the histological, and biochemical changes occurring during this morphogenic process, together with an analysis of transcriptional and metabolic profiles. We also discuss the existence of common molecular factors among three different morphogenic processes: organogenic nodules and somatic embryogenesis, which strictly speaking depend exclusively on intrinsic developmental reprogramming, and legume nitrogen-fixing root nodules, which arises in response to symbiosis. The review of the key factors that participate in hop nodule organogenesis and the comparison with other morphogenic processes may have merit as a study presenting recent advances in complex molecular networks occurring during morphogenesis and together, these provide a rich framework for biotechnology applications.

  20. Computing molecular fluctuations in biochemical reaction systems based on a mechanistic, statistical theory of irreversible processes.

    PubMed

    Kulasiri, Don

    2011-01-01

    We discuss the quantification of molecular fluctuations in the biochemical reaction systems within the context of intracellular processes associated with gene expression. We take the molecular reactions pertaining to circadian rhythms to develop models of molecular fluctuations in this chapter. There are a significant number of studies on stochastic fluctuations in intracellular genetic regulatory networks based on single cell-level experiments. In order to understand the fluctuations associated with the gene expression in circadian rhythm networks, it is important to model the interactions of transcriptional factors with the E-boxes in the promoter regions of some of the genes. The pertinent aspects of a near-equilibrium theory that would integrate the thermodynamical and particle dynamic characteristics of intracellular molecular fluctuations would be discussed, and the theory is extended by using the theory of stochastic differential equations. We then model the fluctuations associated with the promoter regions using general mathematical settings. We implemented ubiquitous Gillespie's algorithms, which are used to simulate stochasticity in biochemical networks, for each of the motifs. Both the theory and the Gillespie's algorithms gave the same results in terms of the time evolution of means and variances of molecular numbers. As biochemical reactions occur far away from equilibrium-hence the use of the Gillespie algorithm-these results suggest that the near-equilibrium theory should be a good approximation for some of the biochemical reactions. © 2011 Elsevier Inc. All rights reserved.

  1. Primary Hyperparathyroidism in Older People: Surgical Treatment with Minimally Invasive Approaches and Outcome

    PubMed Central

    Dobrinja, Chiara; Silvestri, Marta; de Manzini, Nicolò

    2012-01-01

    Introduction. Elderly patients with primary hyperparathyroidism (pHPT) are often not referred to surgery because of their associated comorbidities that may increase surgical risk. The aim of the study was to review indications and results of minimally invasive approach parathyroidectomy in elderly patients to evaluate its impact on outcome. Materials and Methods. All patients of 70 years of age or older undergoing minimally approach parathyroidectomy at our Department from May 2005 to May 2011 were reviewed. Data collected included patients demographic information, biochemical pathology, time elapsed from pHPT diagnosis to surgical intervention, operative findings, complications, and results of postoperative biochemical studies. Results and Discussion. 37 patients were analysed. The average length of stay was 2.8 days. 11 patients were discharged within 24 hours after their operation. Morbidity included 6 transient symptomatic postoperative hypocalcemias while one patient developed a transient laryngeal nerve palsy. Time elapsed from pHPT diagnosis to first surgical visit evidences that the elderly patients were referred after their disease had progressed. Conclusions. Our data show that minimally invasive approach to parathyroid surgery seems to be safe and curative also in elderly patients with few associated risks because of combination of modern preoperative imaging, advances in surgical technique, and advances in anesthesia care. PMID:22737167

  2. A comprehensive review of noninvasive liver fibrosis tests in pediatric nonalcoholic Fatty liver disease.

    PubMed

    Mansoor, Sana; Collyer, Elizabeth; Alkhouri, Naim

    2015-06-01

    Nonalcoholic fatty liver disease (NAFLD) and its spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and fibrosis have been increasing in the pediatric population. The presence and severity of fibrosis in patients with NAFLD are important prognostic factors for the risk of disease progression to cirrhosis. The gold standard for staging liver fibrosis is a liver biopsy. However, given the risks of this procedure, especially in the pediatric population, the development of noninvasive markers to diagnose and monitor progression of NAFLD is desirable. This paper will review recently developed noninvasive methods for diagnosing liver fibrosis in children with NAFLD. These include simple fibrosis scores, advanced biochemical markers, and radiologic imaging studies. Simple fibrosis scores use readily available laboratory tests; available one include AST/ALT ratio, AST to platelet ratio index (APRI), fibrosis (FIB)-4 index, NAFLD fibrosis score (NFS), pediatric NAFLD fibrosis index (PNFI), and pediatric NALFD fibrosis score (PNFS). Advanced biochemical markers include biomarkers of hepatocyte cell death such as cytokeratin 18 fragment levels, and markers of extracellular matrix turnover such as the Enhanced Liver Fibrosis (ELF) test and hyaluronic acid. Radiologic imaging studies estimate liver stiffness as a surrogate for liver fibrosis; these include transient elastography (TE), magnetic resonance elastography (MRE), and acoustic radiation force impulse imaging (ARFI).

  3. Engineering C4 photosynthesis into C3 chassis in the synthetic biology age.

    PubMed

    Schuler, Mara L; Mantegazza, Otho; Weber, Andreas P M

    2016-07-01

    C4 photosynthetic plants outperform C3 plants in hot and arid climates. By concentrating carbon dioxide around Rubisco C4 plants drastically reduce photorespiration. The frequency with which plants evolved C4 photosynthesis independently challenges researchers to unravel the genetic mechanisms underlying this convergent evolutionary switch. The conversion of C3 crops, such as rice, towards C4 photosynthesis is a long-standing goal. Nevertheless, at the present time, in the age of synthetic biology, this still remains a monumental task, partially because the C4 carbon-concentrating biochemical cycle spans two cell types and thus requires specialized anatomy. Here we review the advances in understanding the molecular basis and the evolution of the C4 trait, advances in the last decades that were driven by systems biology methods. In this review we emphasise essential genetic engineering tools needed to translate our theoretical knowledge into engineering approaches. With our current molecular understanding of the biochemical C4 pathway, we propose a simplified rational engineering model exclusively built with known C4 metabolic components. Moreover, we discuss an alternative approach to the progressing international engineering attempts that would combine targeted mutagenesis and directed evolution. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  4. [Biochemical and clinical aspects of advanced oxidation protein products in kidney diseases and metabolic disturbances].

    PubMed

    Piwowar, Agnieszka

    2014-02-06

    Intensified oxidative modification of proteins and increased concentration of advanced oxidation protein products (AOPPs) are confirmed by many experimental investigations in different pathological states, especially these with well-known participation of oxidative stress (OS) in etiopathogenesis but also these with not well recognized its role. Presented data indicate that AOPPs play a significant role in many disorders with chronic background, because of they reflect both intensification of OS and the degree of pathological changes connected with OS in these diseases. This review sets out the clinical and diagnostic aspects of AOPPs in these diseases such as: renal diseases with different etiology, cardiovascular diseases, as well as connected with metabolic disturbances - e.g. diabetes, atherosclerosis or metabolic syndrome. Moreover results of investigation about utility of AOPPs measurement, mainly in plasma/serum, in these diseases are presented. The review and evaluation of application of AOPPs as useful marker in diagnosis, prognosis and monitoring the course of these diseases were performed. This paper also describes the suggested mechanisms of their action which contribute to biochemical and clinic changes undergoing in the condition of increased OS. Diagnostic or prognostic utility of AOPPs are especially indicated in the course of diabetes and its complications (diabetic nephropahy) and cardiovascular diseases.

  5. Recent advances in mathematical modeling of developmental abnormalities using mechanistic information.

    PubMed

    Kavlock, R J

    1997-01-01

    During the last several years, significant changes in the risk assessment process for developmental toxicity of environmental contaminants have begun to emerge. The first of these changes is the development and beginning use of statistically based dose-response models [the benchmark dose (BMD) approach] that better utilize data derived from existing testing approaches. Accompanying this change is the greater emphasis placed on understanding and using mechanistic information to yield more accurate, reliable, and less uncertain risk assessments. The next stage in the evolution of risk assessment will be the use of biologically based dose-response (BBDR) models that begin to build into the statistically based models factors related to the underlying kinetic, biochemical, and/or physiologic processes perturbed by a toxicant. Such models are now emerging from several research laboratories. The introduction of quantitative models and the incorporation of biologic information into them has pointed to the need for even more sophisticated modifications for which we offer the term embryologically based dose-response (EBDR) models. Because these models would be based upon the understanding of normal morphogenesis, they represent a quantum leap in our thinking, but their complexity presents daunting challenges both to the developmental biologist and the developmental toxicologist. Implementation of these models will require extensive communication between developmental toxicologists, molecular embryologists, and biomathematicians. The remarkable progress in the understanding of mammalian embryonic development at the molecular level that has occurred over the last decade combined with advances in computing power and computational models should eventually enable these as yet hypothetical models to be brought into use.

  6. 40 CFR 405.31 - Specialized definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Cultured Products Subcategory § 405.31 Specialized... term “BOD5 input” shall mean the biochemical oxygen demand of the materials entered into process. It...

  7. 40 CFR 405.91 - Specialized definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Condensed Milk Subcategory § 405.91 Specialized... term “BOD5 input” shall mean the biochemical oxygen demand of the materials entered into process. It...

  8. 40 CFR 405.21 - Specialized definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Fluid Products Subcategory § 405.21 Specialized... term “BOD5 input” shall mean the biochemical oxygen demand of the materials entered into process. It...

  9. Run-length encoding graphic rules, biochemically editable designs and steganographical numeric data embedment for DNA-based cryptographical coding system.

    PubMed

    Kawano, Tomonori

    2013-03-01

    There have been a wide variety of approaches for handling the pieces of DNA as the "unplugged" tools for digital information storage and processing, including a series of studies applied to the security-related area, such as DNA-based digital barcodes, water marks and cryptography. In the present article, novel designs of artificial genes as the media for storing the digitally compressed data for images are proposed for bio-computing purpose while natural genes principally encode for proteins. Furthermore, the proposed system allows cryptographical application of DNA through biochemically editable designs with capacity for steganographical numeric data embedment. As a model case of image-coding DNA technique application, numerically and biochemically combined protocols are employed for ciphering the given "passwords" and/or secret numbers using DNA sequences. The "passwords" of interest were decomposed into single letters and translated into the font image coded on the separate DNA chains with both the coding regions in which the images are encoded based on the novel run-length encoding rule, and the non-coding regions designed for biochemical editing and the remodeling processes revealing the hidden orientation of letters composing the original "passwords." The latter processes require the molecular biological tools for digestion and ligation of the fragmented DNA molecules targeting at the polymerase chain reaction-engineered termini of the chains. Lastly, additional protocols for steganographical overwriting of the numeric data of interests over the image-coding DNA are also discussed.

  10. Deterministic modelling and stochastic simulation of biochemical pathways using MATLAB.

    PubMed

    Ullah, M; Schmidt, H; Cho, K H; Wolkenhauer, O

    2006-03-01

    The analysis of complex biochemical networks is conducted in two popular conceptual frameworks for modelling. The deterministic approach requires the solution of ordinary differential equations (ODEs, reaction rate equations) with concentrations as continuous state variables. The stochastic approach involves the simulation of differential-difference equations (chemical master equations, CMEs) with probabilities as variables. This is to generate counts of molecules for chemical species as realisations of random variables drawn from the probability distribution described by the CMEs. Although there are numerous tools available, many of them free, the modelling and simulation environment MATLAB is widely used in the physical and engineering sciences. We describe a collection of MATLAB functions to construct and solve ODEs for deterministic simulation and to implement realisations of CMEs for stochastic simulation using advanced MATLAB coding (Release 14). The program was successfully applied to pathway models from the literature for both cases. The results were compared to implementations using alternative tools for dynamic modelling and simulation of biochemical networks. The aim is to provide a concise set of MATLAB functions that encourage the experimentation with systems biology models. All the script files are available from www.sbi.uni-rostock.de/ publications_matlab-paper.html.

  11. Anaerobic Degradation of Benzene and Polycyclic Aromatic Hydrocarbons.

    PubMed

    Meckenstock, Rainer U; Boll, Matthias; Mouttaki, Housna; Koelschbach, Janina S; Cunha Tarouco, Paola; Weyrauch, Philip; Dong, Xiyang; Himmelberg, Anne M

    2016-01-01

    Aromatic hydrocarbons such as benzene and polycyclic aromatic hydrocarbons (PAHs) are very slowly degraded without molecular oxygen. Here, we review the recent advances in the elucidation of the first known degradation pathways of these environmental hazards. Anaerobic degradation of benzene and PAHs has been successfully documented in the environment by metabolite analysis, compound-specific isotope analysis and microcosm studies. Subsequently, also enrichments and pure cultures were obtained that anaerobically degrade benzene, naphthalene or methylnaphthalene, and even phenanthrene, the largest PAH currently known to be degradable under anoxic conditions. Although such cultures grow very slowly, with doubling times of around 2 weeks, and produce only very little biomass in batch cultures, successful proteogenomic, transcriptomic and biochemical studies revealed novel degradation pathways with exciting biochemical reactions such as for example the carboxylation of naphthalene or the ATP-independent reduction of naphthoyl-coenzyme A. The elucidation of the first anaerobic degradation pathways of naphthalene and methylnaphthalene at the genetic and biochemical level now opens the door to studying the anaerobic metabolism and ecology of anaerobic PAH degraders. This will contribute to assessing the fate of one of the most important contaminant classes in anoxic sediments and aquifers. © 2016 S. Karger AG, Basel.

  12. Design and Application of Sensors for Chemical Cytometry.

    PubMed

    Vickerman, Brianna M; Anttila, Matthew M; Petersen, Brae V; Allbritton, Nancy L; Lawrence, David S

    2018-02-08

    The bulk cell population response to a stimulus, be it a growth factor or a cytotoxic agent, neglects the cell-to-cell variability that can serve as a friend or as a foe in human biology. Biochemical variations among closely related cells furnish the basis for the adaptability of the immune system but also act as the root cause of resistance to chemotherapy by tumors. Consequently, the ability to probe for the presence of key biochemical variables at the single-cell level is now recognized to be of significant biological and biomedical impact. Chemical cytometry has emerged as an ultrasensitive single-cell platform with the flexibility to measure an array of cellular components, ranging from metabolite concentrations to enzyme activities. We briefly review the various chemical cytometry strategies, including recent advances in reporter design, probe and metabolite separation, and detection instrumentation. We also describe strategies for improving intracellular delivery, biochemical specificity, metabolic stability, and detection sensitivity of probes. Recent applications of these strategies to small molecules, lipids, proteins, and other analytes are discussed. Finally, we assess the current scope and limitations of chemical cytometry and discuss areas for future development to meet the needs of single-cell research.

  13. Caloric restriction delays yeast chronological aging by remodeling carbohydrate and lipid metabolism, altering peroxisomal and mitochondrial functionalities, and postponing the onsets of apoptotic and liponecrotic modes of regulated cell death

    PubMed Central

    Arlia-Ciommo, Anthony; Leonov, Anna; Beach, Adam; Richard, Vincent R.; Bourque, Simon D.; Burstein, Michelle T.; Kyryakov, Pavlo; Gomez-Perez, Alejandra; Koupaki, Olivia; Feldman, Rachel; Titorenko, Vladimir I.

    2018-01-01

    A dietary regimen of caloric restriction delays aging in evolutionarily distant eukaryotes, including the budding yeast Saccharomyces cerevisiae. Here, we assessed how caloric restriction influences morphological, biochemical and cell biological properties of chronologically aging yeast advancing through different stages of the aging process. Our findings revealed that this low-calorie diet slows yeast chronological aging by mechanisms that coordinate the spatiotemporal dynamics of various cellular processes before entry into a non-proliferative state and after such entry. Caloric restriction causes a stepwise establishment of an aging-delaying cellular pattern by tuning a network that assimilates the following: 1) pathways of carbohydrate and lipid metabolism; 2) communications between the endoplasmic reticulum, lipid droplets, peroxisomes, mitochondria and the cytosol; and 3) a balance between the processes of mitochondrial fusion and fission. Through different phases of the aging process, the caloric restriction-dependent remodeling of this intricate network 1) postpones the age-related onsets of apoptotic and liponecrotic modes of regulated cell death; and 2) actively increases the chance of cell survival by supporting the maintenance of cellular proteostasis. Because caloric restriction decreases the risk of cell death and actively increases the chance of cell survival throughout chronological lifespan, this dietary intervention extends longevity of chronologically aging yeast. PMID:29662634

  14. Inner ear symptoms and disease: Pathophysiological understanding and therapeutic options

    PubMed Central

    Ciuman, Raphael R.

    2013-01-01

    In recent years, huge advances have taken place in understanding of inner ear pathophysiology causing sensorineural hearing loss, tinnitus, and vertigo. Advances in understanding comprise biochemical and physiological research of stimulus perception and conduction, inner ear homeostasis, and hereditary diseases with underlying genetics. This review describes and tabulates the various causes of inner ear disease and defines inner ear and non-inner ear causes of hearing loss, tinnitus, and vertigo. The aim of this review was to comprehensively breakdown this field of otorhinolaryngology for specialists and non-specialists and to discuss current therapeutic options in distinct diseases and promising research for future therapies, especially pharmaceutic, genetic, or stem cell therapy. PMID:24362017

  15. The heritage of radiotracers for PET

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

    Fowler, J.S.; Wolf, A.P.

    The history of PET research clearly demonstrates that it is advances in chemistry coupled with a detailed examination of the biochemistry of new radiotracers which has allowed the PET method to be applied to new areas of biology and medicine. Radiotracers whose regional distribution reflects glucose metabolism, neutrotransmitter activity and enzyme activity have all required the development of rapid synthetic methods for the radiotracers themselves and the characterization of their biochemical behavior. This article traces some of the advances in the production of labeled precursors and in radiotracer synthesis and evaluation which have shaped the rapidly expanding application of PETmore » to problems in the neurosciences, in cardiology and in oncology. 54 refs.« less

  16. Biotechnological production and applications of Cordyceps militaris, a valued traditional Chinese medicine.

    PubMed

    Cui, Jian Dong

    2015-01-01

    Cordyceps militaris is a potential harborer of biometabolites for herbal drugs. For a long time, C. militaris has gained considerable significance in several clinical and biotechnological applications. Much knowledge has been gathered with regard to the C. militaris's importance in the genetic resources, nutritional and environmental requirements, mating behavior and biochemical pharmacological properties. The complete genome of C. militaris has recently been sequenced. This fungus has been the subject of many reviews, but few have focused on its biotechnological production of bioactive constituents. This mini-review focuses on the recent advances in the biotechnological production of bioactive compositions of C. militaris and the latest advances on novel applications from this laboratory and many others.

  17. Advanced Water Quality Modelling in Marine Systems: Application to the Wadden Sea, the Netherlands

    NASA Astrophysics Data System (ADS)

    Boon, J.; Smits, J. G.

    2006-12-01

    There is an increasing demand for knowledge and models that arise from water management in relation to water quality, sediment quality (ecology) and sediment accumulation (ecomorphology). Recently, models for sediment diagenesis and erosion developed or incorporated by Delft Hydraulics integrates the relevant physical, (bio)chemical and biological processes for the sediment-water exchange of substances. The aim of the diagenesis models is the prediction of both sediment quality and the return fluxes of substances such as nutrients and micropollutants to the overlying water. The resulting so-called DELWAQ-G model is a new, generic version of the water and sediment quality model of the DELFT3D framework. One set of generic water quality process formulations is used to calculate process rates in both water and sediment compartments. DELWAQ-G involves the explicit simulation of sediment layers in the water quality model with state-of-the-art process kinetics. The local conditions in a water layer or sediment layer such as the dissolved oxygen concentration determine if and how individual processes come to expression. New processes were added for sulphate, sulphide, methane and the distribution of the electron-acceptor demand over dissolved oxygen, nitrate, sulphate and carbon dioxide. DELWAQ-G also includes the dispersive and advective transport processes in the sediment and across the sediment-water interface. DELWAQ-G has been applied for the Wadden Sea. A very dynamic tidal and ecologically active estuary with a complex hydrodynamic behaviour located at the north of the Netherlands. The predicted profiles in the sediment reflect the typical interactions of diagenesis processes.

  18. Biochemical quality of the pharmaceutically licensed plasma OctaplasLG after implementation of a novel prion protein (PrPSc) removal technology and reduction of the solvent/detergent (S/D) process time.

    PubMed

    Heger, A; Svae, T-E; Neisser-Svae, A; Jordan, S; Behizad, M; Römisch, J

    2009-10-01

    A new chromatographic step for the selective binding of pathological prion proteins (PrP(Sc)) to an affinity ligand, developed and optimized for PrP(Sc) capture and attached to synthetic resin particles (PRDT, USA; ProMetic BioSciences Ltd, Isle of Man, UK) was implemented into the manufacturing process of the solvent/detergent (S/D) treated biopharmaceutical quality plasma Octaplas. Pilot batches of Octaplas with the implemented chromatographic step [labelled as OctaplasLG (ligand gel)] were manufactured by Octapharma PPGmbH, Vienna, Austria. The biochemical quality was compared directly after manufacturing as well as after 18 months storage. All samples were tested on global coagulation parameters, fibrinogen levels, activities of coagulation factors and protease inhibitors, ADAMTS13 levels, as well as markers of activated coagulation and fibrinolysis. In addition, von Willebrand factor multimeric analysis was performed. The incorporation of this novel chromatography into the large-scale routine manufacturing process was shown to be technically feasible and the performance of the column was assessed to be excellent. The biochemical studies showed that Octaplas and OctaplasLG produced without and with the new column, respectively, demonstrate an identical biochemical quality. OctaplasLG remained stable over a period of 18 months stored frozen. A parallel reduction of the S/D virus inactivation step from 4-4.5 to 1-1.5 h led to significantly higher activities of plasmin inhibitor. The studies confirmed that the affinity ligand chromatography under the developed conditions can be introduced into the Octaplas manufacturing process, as a mean to reduce potentially present PrP(Sc), without hampering the proven quality of this product.

  19. Biochemical study of leaf browning in minimally processed leaves of lettuce (Lactuca sativa L. var. acephala).

    PubMed

    Degl'Innocenti, E; Guidi, L; Pardossi, A; Tognoni, F

    2005-12-28

    A series of biochemical parameters, including the concentration of total ascorbic acid (ASA(tot)) and the activities of phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and peroxidases (PODs), was investigated during cold storage (72 h at 4 degrees C in the dark) in fresh-cut (minimally processed) leaves of two lettuce (Lactuca sativa L. var. acephala) cultivars differing in the susceptibility to tissue browning: Green Salade Bowl (GSB), susceptible, and Red Salade Bowl (RSB), resistant. The two cultivars showed differences also at the biochemical level. The content in ASA(tot) increased in RSB, as a consequence of increased DHA concentration; conversely, ASA(tot) diminished in GSB, in which ASA was not detectable after 72 h of storage, thus suggesting a disappearance of ascorbate (both ASA and DHA) into nonactive forms. The antioxidant capacity (as determined by using FRAP analysis) decreased significantly during storage in RSB, while a strong increase was observed in GSB. PAL activity increased soon after processing reaching a maximum by 3 h, then it declined to a relatively constant value in RSB, while in GSB it showed a tendency to decrease in the first few hours from harvest and processing. POD activity, at least for chlorogenic acid, increased significantly during storage only in GSB.

  20. Characterization of rice (Oryza sativa L.) genotypes on the basis of morpho-physiological and biochemical traits grown under aerobic situation in rainfed ecosystem .

    PubMed

    Kumar, Santosh; Dwivedi, Sharad Kumar; Singh, S S; Kumar, Sanjeev; Sundaram, R K; Shivani; Mall, A K

    2015-07-01

    The objective of the present study was to examine the effect of aerobic situation on yield, physiological and biochemical traits of advanced breeding lines of rice. Experiment was conducted with two set of rice genotypes under two water regimes (aerobic and irrigated), during three consecutive wet seasons 2010-2012. Significant decrease in yield was observed in rice genotypes grown under aerobic situation as compared to the irrigated ones. Promising rice genotypes having the ability to maintain high plant biomass, harvest index, early vegetative vigour, improved physiological and biochemical traits in terms of relative water content (RWC), leaf area index (LAI), total soluble sugar, starch, protien and proline content help to sustain higher grain yield under aerobic situation. The yield gap between aerobic and irrigated rice ranged between 24% to 68%. Grain yield showed positive correlation with harvest index (0.434), test weight (0.647), plant biomass (0.411) and effective tiller numbers (0.473), whereas spikelet sterility was negative associated (-0.380). The current study suggested that promising genotypes viz., IR77298-14-1-2-130-2, IR84899-B-182-3-1-1-2, IR84887-B-157-38-1-1-3 and IR 84899-B-179-1-1-1-2 for aerobic situation, showing yield advantage due to better performance of physiological and biochemical traits, might be adopted in large area of rainfed ecosystem as well as in irrigated areas where water scarcity was a major problem.

  1. 40 CFR 405.61 - Specialized definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Natural and Processed Cheese Subcategory § 405.61... subpart. (b) The term “BOD5 input” shall mean the biochemical oxygen demand of the materials entered into...

  2. Therapeutic peptides: new arsenal against drug resistant pathogens.

    PubMed

    Mok, Wendy W K; Li, Yingfu

    2014-01-01

    Our incessant tug-of-war with multidrug resistant pathogenic bacteria has prompted researchers to explore novel methods of designing therapeutics in order to defend ourselves against infectious diseases. Combined advances in whole genome analysis, bioinformatics algorithms, and biochemical techniques have led to the discovery and subsequent characterization of an abundant array of functional small peptides in microorganisms and multicellular organisms. Typically classified as having 10 to 100 amino acids, many of these peptides have been found to have dual activities, executing important defensive and regulatory functions in their hosts. In higher organisms, such as mammals, plants, and fungi, host defense peptides have been shown to have immunomodulatory and antimicrobial properties. In microbes, certain growth-inhibiting peptides have been linked to the regulation of diverse cellular processes. Examples of these processes include quorum sensing, stress response, cell differentiation, biofilm formation, pathogenesis, and multidrug tolerance. In this review, we will present a comprehensive overview of the discovery, characteristics, and functions of host- and bacteria-derived peptides with antimicrobial activities. The advantages and possible shortcomings of using these peptides as antimicrobial agents and targets will also be discussed. We will further examine current efforts in engineering synthetic peptides to be used as therapeutics and/or drug delivery vehicles.

  3. A transgenic rat with ubiquitous expression of firefly luciferase gene

    NASA Astrophysics Data System (ADS)

    Hakamata, Yoji; Murakami, Takashi; Kobayashi, Eiji

    2006-02-01

    In vivo imaging strategies provide cellular and molecular events in real time that helps us to understand biological processes in living animals. The development of molecular tags such as green fluorescent proteins and luciferase from the firefly Photinus pyralis has lead to a revolution in the visualization of complex biochemical processes. We developed a novel inbred transgenic rat strain containing firefly luciferase based on the transgenic (Tg) technique in rats. This Tg rat expressed the luciferase gene ubiquitously under control of the ROSA26 promoter. Cellular immune responsiveness against the luciferase protein was evaluated using conventional skin grafting and resulted in the long-term acceptance of Tg rat skin on wild-type rats. Strikingly, organ transplant with heart and small bowel demonstrated organ viability and graft survival, suggesting that cells from luciferase-Tg are transplantable to track their fate. Taking advantage of the less immunogenic luciferase, we also tested the role of hepatocyte-infusion in a liver injury model, and bone marrow-derived cells in a skin defect model. Employed in conjunction with modern advances in optical imaging, this luciferase-Tg rat system provides an innovative animal tool and a new means of facilitating biomedical research such as in the case of regeneration medicine.

  4. Optical biopsy of pre-malignant or degenerative lesions: the role of the inflammatory process

    NASA Astrophysics Data System (ADS)

    da Silva Martinho, Herculano

    2011-03-01

    Recent technological advances in fiber optics, light sources, detectors, and molecular biology have stimulated unprecedented development of optical methods to detect pathological changes in tissues. These methods, collectively termed "optical biopsy," are nondestructive in situ and real-time assays. Optical biopsy techniques as fluorescence spectroscopy, polarized light scattering spectroscopy, optical coherence tomography, confocal reflectance microscopy, and Raman spectroscopy had been extensively used to characterize several pathological tissues. In special, Raman spectroscopy technique had been able to probe several biochemical alterations due to pathology development as change in the DNA, glycogen, phospholipid, non-collagenous proteins. All studies claimed that the optical biopsy methods were able to discriminate normal and malignant tissues. However, few studies had been devoted to the discrimination of very common subtle or early pathological states as inflammatory process, which are always present on, e.g., cancer lesion border. In this work we present a systematic comparison of optical biopsy data on several kinds of lesions were inflammatory infiltrates play the role (breast, cervical, and oral lesion). It will be discussed the essential conditions for the optimization of discrimination among normal and alterated states based on statistical analysis.

  5. Azolla domestication towards a biobased economy?

    PubMed

    Brouwer, Paul; Bräutigam, Andrea; Külahoglu, Canan; Tazelaar, Anne O E; Kurz, Samantha; Nierop, Klaas G J; van der Werf, Adrie; Weber, Andreas P M; Schluepmann, Henriette

    2014-05-01

    Due to its phenomenal growth requiring neither nitrogen fertilizer nor arable land and its biomass composition, the mosquito fern Azolla is a candidate crop to yield food, fuels and chemicals sustainably. To advance Azolla domestication, we research its dissemination, storage and transcriptome. Methods for dissemination, cross-fertilization and cryopreservation of the symbiosis Azolla filiculoides-Nostoc azollae are tested based on the fern spores. To study molecular processes in Azolla including spore induction, a database of 37 649 unigenes from RNAseq of microsporocarps, megasporocarps and sporophytes was assembled, then validated. Spores obtained year-round germinated in vitro within 26 d. In vitro fertilization rates reached 25%. Cryopreservation permitted storage for at least 7 months. The unigene database entirely covered central metabolism and to a large degree covered cellular processes and regulatory networks. Analysis of genes engaged in transition to sexual reproduction revealed a FLOWERING LOCUS T-like protein in ferns with special features induced in sporulating Azolla fronds. Although domestication of a fern-cyanobacteria symbiosis may seem a daunting task, we conclude that the time is ripe and that results generated will serve to more widely access biochemicals in fern biomass for a biobased economy. No claim to original European Union works. New Phytologist © 2014 New Phytologist Trust.

  6. Genome editing: the breakthrough technology for inherited retinal disease?

    PubMed

    Smith, Andrew J; Carter, Stephen P; Kennedy, Breandán N

    2017-10-01

    Genetic alterations resulting in a dysfunctional retinal pigment epithelium and/or degenerating photoreceptors cause impaired vision. These juxtaposed cells in the retina of the posterior eye are crucial for the visual cycle or phototransduction. Deficits in these biochemical processes perturb neural processing of images capturing the external environment. Notably, there is a distinct lack of clinically approved pharmacological, cell- or gene-based therapies for inherited retinal disease. Gene editing technologies are rapidly advancing as a realistic therapeutic option. Areas covered: Recent discovery of endonuclease-mediated gene editing technologies has culminated in a surge of investigations into their therapeutic potential. In this review, the authors discuss gene editing technologies and their applicability in treating inherited retinal diseases, the limitations of the technology and the research obstacles to overcome before editing a patient's genome becomes a viable treatment option. Expert opinion: The ability to strategically edit a patient's genome constitutes a treatment revolution. However, concerns remain over the safety and efficacy of either transplanting iPSC-derived retinal cells following ex vivo gene editing, or with direct gene editing in vivo. Ultimately, further refinements to improve efficacy and safety profiles are paramount for gene editing to emerge as a widely available treatment option.

  7. The pearl oyster Pinctada fucata martensii genome and multi-omic analyses provide insights into biomineralization

    PubMed Central

    Fan, Guangyi; Jiao, Yu; Zhang, He; Huang, Ronglian; Zheng, Zhe; Bian, Chao; Deng, Yuewen; Wang, Qingheng; Wang, Zhongduo; Liang, Xinming; Liang, Haiying; Shi, Chengcheng; Zhao, Xiaoxia; Sun, Fengming; Hao, Ruijuan; Bai, Jie; Liu, Jialiang; Chen, Wenbin; Liang, Jinlian; Liu, Weiqing; Xu, Zhe; Shi, Qiong; Xu, Xun

    2017-01-01

    Abstract Nacre, the iridescent material found in pearls and shells of molluscs, is formed through an extraordinary process of matrix-assisted biomineralization. Despite recent advances, many aspects of the biomineralization process and its evolutionary origin remain unknown. The pearl oyster Pinctada fucata martensii is a well-known master of biomineralization, but the molecular mechanisms that underlie its production of shells and pearls are not fully understood. We sequenced the highly polymorphic genome of the pearl oyster and conducted multi-omic and biochemical studies to probe nacre formation. We identified a large set of novel proteins participating in matrix-framework formation, many in expanded families, including components similar to that found in vertebrate bones such as collagen-related VWA-containing proteins, chondroitin sulfotransferases, and regulatory elements. Considering that there are only collagen-based matrices in vertebrate bones and chitin-based matrices in most invertebrate skeletons, the presence of both chitin and elements of collagen-based matrices in nacre suggests that elements of chitin- and collagen-based matrices have deep roots and might be part of an ancient biomineralizing matrix. Our results expand the current shell matrix-framework model and provide new insights into the evolution of diverse biomineralization systems. PMID:28873964

  8. Biotechnology and genetic engineering in the new drug development. Part I. DNA technology and recombinant proteins.

    PubMed

    Stryjewska, Agnieszka; Kiepura, Katarzyna; Librowski, Tadeusz; Lochyński, Stanisław

    2013-01-01

    Pharmaceutical biotechnology has a long tradition and is rooted in the last century, first exemplified by penicillin and streptomycin as low molecular weight biosynthetic compounds. Today, pharmaceutical biotechnology still has its fundamentals in fermentation and bioprocessing, but the paradigmatic change affected by biotechnology and pharmaceutical sciences has led to an updated definition. The biotechnology revolution redrew the research, development, production and even marketing processes of drugs. Powerful new instruments and biotechnology related scientific disciplines (genomics, proteomics) make it possible to examine and exploit the behavior of proteins and molecules. Recombinant DNA (rDNA) technologies (genetic, protein, and metabolic engineering) allow the production of a wide range of peptides, proteins, and biochemicals from naturally nonproducing cells. This technology, now approximately 25 years old, is becoming one of the most important technologies developed in the 20(th) century. Pharmaceutical products and industrial enzymes were the first biotech products on the world market made by means of rDNA. Despite important advances regarding rDNA applications in mammalian cells, yeasts still represent attractive hosts for the production of heterologous proteins. In this review we describe these processes.

  9. Single-cell mechanical phenotype is an intrinsic marker of reprogramming and differentiation along the mouse neural lineage.

    PubMed

    Urbanska, Marta; Winzi, Maria; Neumann, Katrin; Abuhattum, Shada; Rosendahl, Philipp; Müller, Paul; Taubenberger, Anna; Anastassiadis, Konstantinos; Guck, Jochen

    2017-12-01

    Cellular reprogramming is a dedifferentiation process during which cells continuously undergo phenotypical remodeling. Although the genetic and biochemical details of this remodeling are fairly well understood, little is known about the change in cell mechanical properties during the process. In this study, we investigated changes in the mechanical phenotype of murine fetal neural progenitor cells (fNPCs) during reprogramming to induced pluripotent stem cells (iPSCs). We find that fNPCs become progressively stiffer en route to pluripotency, and that this stiffening is mirrored by iPSCs becoming more compliant during differentiation towards the neural lineage. Furthermore, we show that the mechanical phenotype of iPSCs is comparable with that of embryonic stem cells. These results suggest that mechanical properties of cells are inherent to their developmental stage. They also reveal that pluripotent cells can differentiate towards a more compliant phenotype, which challenges the view that pluripotent stem cells are less stiff than any cells more advanced developmentally. Finally, our study indicates that the cell mechanical phenotype might be utilized as an inherent biophysical marker of pluripotent stem cells. © 2017. Published by The Company of Biologists Ltd.

  10. Hyperbaric Oxygen, Vasculogenic Stem Cells, and Wound Healing

    PubMed Central

    Fosen, Katina M.

    2014-01-01

    Abstract Significance: Oxidative stress is recognized as playing a role in stem cell mobilization from peripheral sites and also cell function. Recent Advances: This review focuses on the impact of hyperoxia on vasculogenic stem cells and elements of wound healing. Critical Issues: Components of the wound-healing process in which oxidative stress has a positive impact on the various cells involved in wound healing are highlighted. A slightly different view of wound-healing physiology is adopted by departing from the often used notion of sequential stages: hemostatic, inflammatory, proliferative, and remodeling and instead organizes the cascade of wound healing as overlapping events or waves pertaining to reactive oxygen species, lactate, and nitric oxide. This was done because hyperoxia has effects of a number of cell signaling events that converge to influence cell recruitment/chemotaxis and gene regulation/protein synthesis responses which mediate wound healing. Future Directions: Our alternative perspective of the stages of wound healing eases recognition of the multiple sites where oxidative stress has an impact on wound healing. This aids the focus on mechanistic events and the interplay among various cell types and biochemical processes. It also highlights the areas where additional research is needed. Antioxid. Redox Signal. 21, 1634–1647. PMID:24730726

  11. Effect of altitude on biochemical composition and quality of green arabica coffee beans can be affected by shade and postharvest processing method.

    PubMed

    Worku, Mohammed; de Meulenaer, Bruno; Duchateau, Luc; Boeckx, Pascal

    2018-03-01

    Although various studies have assessed altitude, shade and postharvest processing effects on biochemical content and quality of coffee beans, data on their interactions are scarce. The individual and interactive effects of these factors on the caffeine, chlorogenic acids (CGA) and sucrose contents as well as physical and sensory qualities of green coffee beans from large plantations in southwestern Ethiopia were evaluated. Caffeine and CGA contents decreased with increasing altitude; they respectively declined 0.12 and 1.23gkg -1 100m -1 . Sucrose content increased with altitude; however, the altitude effect was significant for wet-processed beans (3.02gkg -1 100m -1 ), but not for dry-processed beans (0.36g kg -1 100m -1 ). Similarly, sucrose content increased with altitude with much stronger effect for coffee grown without shade (2.11gkg -1 100m -1 ) compared to coffee grown under shade (0.93gkg -1 100m -1 ). Acidity increased with altitude when coffee was grown under shade (0.22 points 100m -1 ), but no significant altitude effect was observed on coffee grown without shade. Beans grown without shade showed a higher physical quality score for dry (37.2) than for wet processing (29.1). These results generally underline the complex interaction effects between altitude and shade or postharvest processing on biochemical composition and quality of green arabica coffee beans. Copyright © 2017. Published by Elsevier Ltd.

  12. Hyperspectral Remote Sensing of Vegetation:Knowledge Gain and Knowledge Gap after 40 years of research

    NASA Astrophysics Data System (ADS)

    Thenkabail, P. S.; Huete, A. R.

    2012-12-01

    This presentation summarizes the advances made over 40+ years in understanding, modeling, and mapping terrestrial vegetation as reported in the new book on "Hyperspectral Remote Sensing of Vegetation" (Publisher: Taylor and Francis inc.). The advent of spaceborne hyperspectral sensors or imaging spectroscopy (e.g., NASA's Hyperion, ESA's PROBA, and upcoming Italy's ASI's Prisma, Germany's DLR's EnMAP, Japanese HIUSI, NASA's HyspIRI) as well as the advancements in processing large volumes of hyperspectral data have generated tremendous interest in expanding the hyperspectral applications' knowledge base to large areas. Advances made in using hyperspectral data, relative to broadband spectral data, include: (a) significantly improved characterization and modeling of a wide array of biophysical and biochemical properties of vegetation, (b) the ability to discriminate plant species and vegetation types with high degree of accuracy, (c) reduced uncertainty in determining net primary productivity or carbon assessments from terrestrial vegetation, (d) improved crop productivity and water productivity models, (e) the ability to assess stress resulting from causes such as management practices, pests and disease, water deficit or water excess, and (f) establishing wavebands and indices with greater sensitivity for analyzing vegetation characteristics. Current state of knowledge on hyperspectral narrowbands (HNBs) for agricultural and vegetation studies inferred from the Book entitled hyperspectral remote sensing of vegetation by Thenkabail et al., 2011. Six study areas of the World for which we have extensive data from field spectroradiometers for 8 major world crops (wheat, corn, rice, barley, soybeans, pulses, and cotton). Approx. 10,500 such data points will be used in crop modeling and in building spectral libraries.

  13. Metabolomics in transfusion medicine.

    PubMed

    Nemkov, Travis; Hansen, Kirk C; Dumont, Larry J; D'Alessandro, Angelo

    2016-04-01

    Biochemical investigations on the regulatory mechanisms of red blood cell (RBC) and platelet (PLT) metabolism have fostered a century of advances in the field of transfusion medicine. Owing to these advances, storage of RBCs and PLT concentrates has become a lifesaving practice in clinical and military settings. There, however, remains room for improvement, especially with regard to the introduction of novel storage and/or rejuvenation solutions, alternative cell processing strategies (e.g., pathogen inactivation technologies), and quality testing (e.g., evaluation of novel containers with alternative plasticizers). Recent advancements in mass spectrometry-based metabolomics and systems biology, the bioinformatics integration of omics data, promise to speed up the design and testing of innovative storage strategies developed to improve the quality, safety, and effectiveness of blood products. Here we review the currently available metabolomics technologies and briefly describe the routine workflow for transfusion medicine-relevant studies. The goal is to provide transfusion medicine experts with adequate tools to navigate through the otherwise overwhelming amount of metabolomics data burgeoning in the field during the past few years. Descriptive metabolomics data have represented the first step omics researchers have taken into the field of transfusion medicine. However, to up the ante, clinical and omics experts will need to merge their expertise to investigate correlative and mechanistic relationships among metabolic variables and transfusion-relevant variables, such as 24-hour in vivo recovery for transfused RBCs. Integration with systems biology models will potentially allow for in silico prediction of metabolic phenotypes, thus streamlining the design and testing of alternative storage strategies and/or solutions. © 2015 AABB.

  14. Advanced biosensing methodologies developed for evaluating performance quality and safety of emerging biophotonics technologies and medical devices (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Ilev, Ilko K.; Walker, Bennett; Calhoun, William; Hassan, Moinuddin

    2016-03-01

    Biophotonics is an emerging field in modern biomedical technology that has opened up new horizons for transfer of state-of-the-art techniques from the areas of lasers, fiber optics and biomedical optics to the life sciences and medicine. This field continues to vastly expand with advanced developments across the entire spectrum of biomedical applications ranging from fundamental "bench" laboratory studies to clinical patient "bedside" diagnostics and therapeutics. However, in order to translate these technologies to clinical device applications, the scientific and industrial community, and FDA are facing the requirement for a thorough evaluation and review of laser radiation safety and efficacy concerns. In many cases, however, the review process is complicated due the lack of effective means and standard test methods to precisely analyze safety and effectiveness of some of the newly developed biophotonics techniques and devices. There is, therefore, an immediate public health need for new test protocols, guidance documents and standard test methods to precisely evaluate fundamental characteristics, performance quality and safety of these technologies and devices. Here, we will overview our recent developments of novel test methodologies for safety and efficacy evaluation of some emerging biophotonics technologies and medical devices. These methodologies are based on integrating the advanced features of state-of-the-art optical sensor technologies and approaches such as high-resolution fiber-optic sensing, confocal and optical coherence tomography imaging, and infrared spectroscopy. The presentation will also illustrate some methodologies developed and implemented for testing intraocular lens implants, biochemical contaminations of medical devices, ultrahigh-resolution nanoscopy, and femtosecond laser therapeutics.

  15. An Overview of Biofield Devices

    PubMed Central

    Muehsam, David; Chevalier, Gaétan; Barsotti, Tiffany

    2015-01-01

    Advances in biophysics, biology, functional genomics, neuroscience, psychology, psychoneuroimmunology, and other fields suggest the existence of a subtle system of “biofield” interactions that organize biological processes from the subatomic, atomic, molecular, cellular, and organismic to the interpersonal and cosmic levels. Biofield interactions may bring about regulation of biochemical, cellular, and neurological processes through means related to electromagnetism, quantum fields, and perhaps other means of modulating biological activity and information flow. The biofield paradigm, in contrast to a reductionist, chemistry-centered viewpoint, emphasizes the informational content of biological processes; biofield interactions are thought to operate in part via low-energy or “subtle” processes such as weak, nonthermal electromagnetic fields (EMFs) or processes potentially related to consciousness and nonlocality. Biofield interactions may also operate through or be reflected in more well-understood informational processes found in electroencephalographic (EEG) and electrocardiographic (ECG) data. Recent advances have led to the development of a wide variety of therapeutic and diagnostic biofield devices, defined as physical instruments best understood from the viewpoint of a biofield paradigm. Here, we provide a broad overview of biofield devices, with emphasis on those devices for which solid, peer-reviewed evidence exists. A subset of these devices, such as those based upon EEG- and ECG-based heart rate variability, function via mechanisms that are well understood and are widely employed in clinical settings. Other device modalities, such a gas discharge visualization and biophoton emission, appear to operate through incompletely understood mechanisms and have unclear clinical significance. Device modes of operation include EMF-light, EMF-heat, EMF-nonthermal, electrical current, vibration and sound, physical and mechanical, intentionality and nonlocality, gas and plasma, and other (mode of operation not well-understood). Methodological issues in device development and interfaces for future interdisciplinary research are discussed. Devices play prominent cultural and scientific roles in our society, and it is likely that device technologies will be one of the most influential access points for the furthering of biofield research and the dissemination of biofield concepts. This developing field of study presents new areas of research that have many important implications for both basic science and clinical medicine. PMID:26665041

  16. An Overview of Biofield Devices.

    PubMed

    Muehsam, David; Chevalier, Gaétan; Barsotti, Tiffany; Gurfein, Blake T

    2015-11-01

    Advances in biophysics, biology, functional genomics, neuroscience, psychology, psychoneuroimmunology, and other fields suggest the existence of a subtle system of "biofield" interactions that organize biological processes from the subatomic, atomic, molecular, cellular, and organismic to the interpersonal and cosmic levels. Biofield interactions may bring about regulation of biochemical, cellular, and neurological processes through means related to electromagnetism, quantum fields, and perhaps other means of modulating biological activity and information flow. The biofield paradigm, in contrast to a reductionist, chemistry-centered viewpoint, emphasizes the informational content of biological processes; biofield interactions are thought to operate in part via low-energy or "subtle" processes such as weak, nonthermal electromagnetic fields (EMFs) or processes potentially related to consciousness and nonlocality. Biofield interactions may also operate through or be reflected in more well-understood informational processes found in electroencephalographic (EEG) and electrocardiographic (ECG) data. Recent advances have led to the development of a wide variety of therapeutic and diagnostic biofield devices, defined as physical instruments best understood from the viewpoint of a biofield paradigm. Here, we provide a broad overview of biofield devices, with emphasis on those devices for which solid, peer-reviewed evidence exists. A subset of these devices, such as those based upon EEG- and ECG-based heart rate variability, function via mechanisms that are well understood and are widely employed in clinical settings. Other device modalities, such a gas discharge visualization and biophoton emission, appear to operate through incompletely understood mechanisms and have unclear clinical significance. Device modes of operation include EMF-light, EMF-heat, EMF-nonthermal, electrical current, vibration and sound, physical and mechanical, intentionality and nonlocality, gas and plasma, and other (mode of operation not well-understood). Methodological issues in device development and interfaces for future interdisciplinary research are discussed. Devices play prominent cultural and scientific roles in our society, and it is likely that device technologies will be one of the most influential access points for the furthering of biofield research and the dissemination of biofield concepts. This developing field of study presents new areas of research that have many important implications for both basic science and clinical medicine.

  17. An Inductive Logic Programming Approach to Validate Hexose Binding Biochemical Knowledge.

    PubMed

    Nassif, Houssam; Al-Ali, Hassan; Khuri, Sawsan; Keirouz, Walid; Page, David

    2010-01-01

    Hexoses are simple sugars that play a key role in many cellular pathways, and in the regulation of development and disease mechanisms. Current protein-sugar computational models are based, at least partially, on prior biochemical findings and knowledge. They incorporate different parts of these findings in predictive black-box models. We investigate the empirical support for biochemical findings by comparing Inductive Logic Programming (ILP) induced rules to actual biochemical results. We mine the Protein Data Bank for a representative data set of hexose binding sites, non-hexose binding sites and surface grooves. We build an ILP model of hexose-binding sites and evaluate our results against several baseline machine learning classifiers. Our method achieves an accuracy similar to that of other black-box classifiers while providing insight into the discriminating process. In addition, it confirms wet-lab findings and reveals a previously unreported Trp-Glu amino acids dependency.

  18. Performance limits and trade-offs in entropy-driven biochemical computers.

    PubMed

    Chu, Dominique

    2018-04-14

    It is now widely accepted that biochemical reaction networks can perform computations. Examples are kinetic proof reading, gene regulation, or signalling networks. For many of these systems it was found that their computational performance is limited by a trade-off between the metabolic cost, the speed and the accuracy of the computation. In order to gain insight into the origins of these trade-offs, we consider entropy-driven computers as a model of biochemical computation. Using tools from stochastic thermodynamics, we show that entropy-driven computation is subject to a trade-off between accuracy and metabolic cost, but does not involve time-trade-offs. Time trade-offs appear when it is taken into account that the result of the computation needs to be measured in order to be known. We argue that this measurement process, although usually ignored, is a major contributor to the cost of biochemical computation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Vitreous humour - routine or alternative material for analysis in forensic medicine.

    PubMed

    Markowska, Joanna; Szopa, Monika; Zawadzki, Marcin; Piekoszewski, Wojciech

    2017-01-01

    Biological materials used in toxicological analyses in forensic medicine traditionally include blood, urine and vitreous humour. Forensic use of the vitreous body is mostly due to the need to assess the endogenous concentration of ethyl alcohol in the process of human body decomposition. The vitreous body is an underestimated biological material, even though its biochemical properties and anatomical location make it suitable for specific forensic toxicology tests as a reliable material for the preparation of forensic expert opinions. Based on the available literature the paper gathers information on the biochemical structure of the vitreous body, ways to secure the material after collection and its use in postmortem diagnostics. Specific applications of the vitreous humour for biochemical and toxicological tests are discussed, with a focus on its advantages and limitations in forensic medical assessment which are attributable to its biochemical properties, anatomical location and limited scientific studies on the distribution of xenobiotics in the vitreous body.

  20. CADLIVE toolbox for MATLAB: automatic dynamic modeling of biochemical networks with comprehensive system analysis.

    PubMed

    Inoue, Kentaro; Maeda, Kazuhiro; Miyabe, Takaaki; Matsuoka, Yu; Kurata, Hiroyuki

    2014-09-01

    Mathematical modeling has become a standard technique to understand the dynamics of complex biochemical systems. To promote the modeling, we had developed the CADLIVE dynamic simulator that automatically converted a biochemical map into its associated mathematical model, simulated its dynamic behaviors and analyzed its robustness. To enhance the feasibility by CADLIVE and extend its functions, we propose the CADLIVE toolbox available for MATLAB, which implements not only the existing functions of the CADLIVE dynamic simulator, but also the latest tools including global parameter search methods with robustness analysis. The seamless, bottom-up processes consisting of biochemical network construction, automatic construction of its dynamic model, simulation, optimization, and S-system analysis greatly facilitate dynamic modeling, contributing to the research of systems biology and synthetic biology. This application can be freely downloaded from http://www.cadlive.jp/CADLIVE_MATLAB/ together with an instruction.

  1. TERMINAL ELECTRON ACCEPTING PROCESSES IN THE ALLUVIAL SEDIMENTS OF A HEADWATER STREAM

    EPA Science Inventory

    Chemical fluxes between catchments and streams are influenced by biochemical processes in the groundwater-stream water (GW-SW) ecotone, the interface between stream surface water and groundwater. Terminal electron accepting processes (TEAPs) that are utilized in respiration of ...

  2. Development of efficient, integrated cellulosic biorefineries : LDRD final report.

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

    Teh, Kwee-Yan; Hecht, Ethan S.; Shaddix, Christopher R.

    2010-09-01

    Cellulosic ethanol, generated from lignocellulosic biomass sources such as grasses and trees, is a promising alternative to conventional starch- and sugar-based ethanol production in terms of potential production quantities, CO{sub 2} impact, and economic competitiveness. In addition, cellulosic ethanol can be generated (at least in principle) without competing with food production. However, approximately 1/3 of the lignocellulosic biomass material (including all of the lignin) cannot be converted to ethanol through biochemical means and must be extracted at some point in the biochemical process. In this project we gathered basic information on the prospects for utilizing this lignin residue material inmore » thermochemical conversion processes to improve the overall energy efficiency or liquid fuel production capacity of cellulosic biorefineries. Two existing pretreatment approaches, soaking in aqueous ammonia (SAA) and the Arkenol (strong sulfuric acid) process, were implemented at Sandia and used to generated suitable quantities of residue material from corn stover and eucalyptus feedstocks for subsequent thermochemical research. A third, novel technique, using ionic liquids (IL) was investigated by Sandia researchers at the Joint Bioenergy Institute (JBEI), but was not successful in isolating sufficient lignin residue. Additional residue material for thermochemical research was supplied from the dilute-acid simultaneous saccharification/fermentation (SSF) pilot-scale process at the National Renewable Energy Laboratory (NREL). The high-temperature volatiles yields of the different residues were measured, as were the char combustion reactivities. The residue chars showed slightly lower reactivity than raw biomass char, except for the SSF residue, which had substantially lower reactivity. Exergy analysis was applied to the NREL standard process design model for thermochemical ethanol production and from a prototypical dedicated biochemical process, with process data supplied by a recent report from the National Research Council (NRC). The thermochemical system analysis revealed that most of the system inefficiency is associated with the gasification process and subsequent tar reforming step. For the biochemical process, the steam generation from residue combustion, providing the requisite heating for the conventional pretreatment and alcohol distillation processes, was shown to dominate the exergy loss. An overall energy balance with different potential distillation energy requirements shows that as much as 30% of the biomass energy content may be available in the future as a feedstock for thermochemical production of liquid fuels.« less

  3. Recent Advances in Archaeological Chemistry: A Summary of the Three Major Papers Presented as an Introduction to the Archeological Chemistry Symposium, Anaheim, California

    NASA Astrophysics Data System (ADS)

    Chen, Wen; Orna, Mary Virginia; O. S., U.

    1996-06-01

    Modern archaeology is fully supported by advances in science and technology. With the development of chemical and biochemical analyses, the task of the archaeological chemist has become more complex than ever over the past decade. In the symposium on archaeological chemistry held at the American Chemical Society National Meeting in Anaheim, California, from April 2-6, 1995, three noted scientists who have made seminal contributions in their respective fields presented an accompanying pedagogical symposium to provide introductory information on how modern chemistry and biochemistry have revolutionized modern archaeological studies at a molecular level. These three scientists and their presentations were: Stanley Ambrose, "Advances in Stable Isotope Analysis in Dietary Reconstruction"; Svante Pääbo, "Ancient DNA as a Means to Study the History of Humans and Extinct Creatures"; and Robert Hedges, "Radiocarbon Dating of Archaeological Bone by Accelerator Mass Spectrometry.

  4. Advances in the Diagnosis and Management of Inflammatory Bowel Disease: Challenges and Uncertainties

    PubMed Central

    Mosli, Mahmoud; Al Beshir, Mohammad; Al-Judaibi, Bandar; Al-Ameel, Turki; Saleem, Abdulaziz; Bessissow, Talat; Ghosh, Subrata; Almadi, Majid

    2014-01-01

    Over the past two decades, several advances have been made in the management of patients with inflammatory bowel disease (IBD) from both evaluative and therapeutic perspectives. This review discusses the medical advancements that have recently been made as the standard of care for managing patients with ulcerative colitis (UC) and Crohn's Disease (CD) and to identify the challenges associated with implementing their use in clinical practice. A comprehensive literature search of the major databases (PubMed and Embase) was conducted for all recent scientific papers (1990–2013) giving the recent updates on the management of IBD and the data were extracted. The reported advancements in managing IBD range from diagnostic and evaluative tools, such as genetic tests, biochemical surrogate markers of activity, endoscopic techniques, and radiological modalities, to therapeutic advances, which encompass medical, endoscopic, and surgical interventions. There are limited studies addressing the cost-effectiveness and the impact that these advances have had on medical practice. The majority of the advances developed for managing IBD, while considered instrumental by some IBD experts in improving patient care, have questionable applications due to constraints of cost, lack of availability, and most importantly, insufficient evidence that supports their role in improving important long-term health-related outcomes. PMID:24705146

  5. Exercise-induced biochemical changes and their potential influence on cancer: a scientific review

    PubMed Central

    Thomas, Robert James; Kenfield, Stacey A; Jimenez, Alfonso

    2017-01-01

    Aim To review and discuss the available international literature regarding the indirect and direct biochemical mechanisms that occur after exercise, which could positively, or negatively, influence oncogenic pathways. Methods The PubMed, MEDLINE, Embase and Cochrane libraries were searched for papers up to July 2016 addressing biochemical changes after exercise with a particular reference to cancer. The three authors independently assessed their appropriateness for inclusion in this review based on their scientific quality and relevance. Results 168 papers were selected and categorised into indirect and direct biochemical pathways. The indirect effects included changes in vitamin D, weight reduction, sunlight exposure and improved mood. The direct effects included insulin-like growth factor, epigenetic effects on gene expression and DNA repair, vasoactive intestinal peptide, oxidative stress and antioxidant pathways, heat shock proteins, testosterone, irisin, immunity, chronic inflammation and prostaglandins, energy metabolism and insulin resistance. Summary Exercise is one of several lifestyle factors known to lower the risk of developing cancer and is associated with lower relapse rates and better survival. This review highlights the numerous biochemical processes, which explain these potential anticancer benefits. PMID:27993842

  6. Diffusion of Small Sticky Nanoparticles in a Polymer Melt: A Dynamic Light Scattering Study

    NASA Astrophysics Data System (ADS)

    Carroll, Bobby; Bocharova, Vera; Cheng, Shiwang; Yamamoto, Umi; Kisliuk, Alex; Schweizer, Ken; Sokolov, Alexei

    The study of dynamics in complex fluids such as polymers has gained a broad interest in advanced materials and biomedical applications. Of particular interest is the motion of nanoparticles in these systems, which influences the mechanical and structural properties of composite materials, properties of colloidal systems, and biochemical processes in biological systems. Theoretical work predicts a violation of Stokes-Einstein (SE) relationship for diffusion of small nanoparticles in strongly-entangled polymer melt systems, with diffusion of nanoparticles much faster than expected DSE. It is attributed to differences between local and macroscopic viscosity. In this study, the diffusion of nanoparticles in polymer melts below and above entanglement molecular weight is measured using dynamic light scattering. The measured results are compared with simulations that provide quantitative predictions for SE violations. Our results are two-fold: (1) diffusion at lower molecular weights is slower than expected DSE due to chain absorption; and (2) diffusion becomes much (20 times) faster than DSE, at higher entanglements due to a reduced local viscosity.

  7. Stem Cell Therapy: Repurposing Cell-Based Regenerative Medicine Beyond Cell Replacement.

    PubMed

    Napoli, Eleonora; Lippert, Trenton; Borlongan, Cesar V

    2018-02-27

    Stem cells exhibit simple and naive cellular features, yet their exact purpose for regenerative medicine continues to elude even the most elegantly designed research paradigms from developmental biology to clinical therapeutics. Based on their capacity to divide indefinitely and their dynamic differentiation into any type of tissue, the advent of transplantable stem cells has offered a potential treatment for aging-related and injury-mediated diseases. Recent laboratory evidence has demonstrated that transplanted human neural stem cells facilitate endogenous reparative mechanisms by initiating multiple regenerative processes in the brain neurogenic areas. Within these highly proliferative niches reside a myriad of potent regenerative molecules, including anti-inflammatory cytokines, proteomes, and neurotrophic factors, altogether representing a biochemical cocktail vital for restoring brain function in the aging and diseased brain. Here, we advance the concept of therapeutically repurposing stem cells not towards cell replacement per se, but rather exploiting the cells' intrinsic properties to serve as the host brain regenerative catalysts.

  8. Mammalian O-Mannosylation Pathway: Glycan Structures, Enzymes, and Protein Substrates

    PubMed Central

    2015-01-01

    The mammalian O-mannosylation pathway for protein post-translational modification is intricately involved in modulating cell–matrix interactions in the musculature and nervous system. Defects in enzymes of this biosynthetic pathway are causative for multiple forms of congenital muscular dystophy. The application of advanced genetic and biochemical technologies has resulted in remarkable progress in this field over the past few years, culminating with the publication of three landmark papers in 2013 alone. In this review, we will highlight recent progress focusing on the dramatic expansion of the set of genes known to be involved in O-mannosylation and disease processes, the concurrent acceleration of the rate of O-mannosylation pathway protein functional assignments, the tremendous increase in the number of proteins now known to be modified by O-mannosylation, and the recent progress in protein O-mannose glycan quantification and site assignment. Also, we attempt to highlight key outstanding questions raised by this abundance of new information. PMID:24786756

  9. S-nitrosothiols and the S-nitrosoproteome of the cardiovascular system.

    PubMed

    Maron, Bradley A; Tang, Shiow-Shih; Loscalzo, Joseph

    2013-01-20

    Since their discovery in the early 1990's, S-nitrosylated proteins have been increasingly recognized as important determinants of many biochemical processes. Specifically, S-nitrosothiols in the cardiovascular system exert many actions, including promoting vasodilation, inhibiting platelet aggregation, and regulating Ca(2+) channel function that influences myocyte contractility and electrophysiologic stability. Contemporary developments in liquid chromatography-mass spectrometry methods, the development of biotin- and His-tag switch assays, and the availability of cyanide dye-labeling for S-nitrosothiol detection in vitro have increased significantly the identification of a number of cardiovascular protein targets of S-nitrosylation in vivo. Recent analyses using modern S-nitrosothiol detection techniques have revealed the mechanistic significance of S-nitrosylation to the pathophysiology of numerous cardiovascular diseases, including essential hypertension, pulmonary hypertension, ischemic heart disease, stroke, and congestive heart failure, among others. Despite enhanced insight into S-nitrosothiol biochemistry, translating these advances into beneficial pharmacotherapies for patients with cardiovascular diseases remains a primary as-yet unmet goal for investigators within the field.

  10. The S100P/RAGE signaling pathway regulates expression of microRNA-21 in colon cancer cells.

    PubMed

    Mercado-Pimentel, Melania E; Onyeagucha, Benjamin C; Li, Qing; Pimentel, Angel C; Jandova, Jana; Nelson, Mark A

    2015-08-19

    S100P signaling through the receptor for advanced glycation end-products (RAGE) contributes to colon cancer invasion and metastasis, but the mechanistic features of this process are obscure. Here, we investigate whether activation of S100P/RAGE signaling regulates oncogenic microRNA-21 (miR-21). We show that exogenous S100P up-regulates miR-21 levels in human colon cancer cells, whereas knockdown of S100P results in a decrease of miR-21. Furthermore, blockage of RAGE with anti-RAGE antibody suppresses S100P induction of miR-21. In addition, we found that S100P induction of miR-21 expression involves ERK and is suppressed by the MEK inhibitor U0126. Also, S100P treatment stimulates the enrichment of c-Fos, and AP-1 family members, at the miR-21 gene promoter. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  11. Nitric Oxide Homeostasis in Neurodegenerative Diseases.

    PubMed

    Hannibal, Luciana

    2016-01-01

    The role of nitric oxide in the pathogenesis and progression of neurodegenerative illnesses such as Parkinson's and Alzheimer's diseases has become prominent over the years. Increased activity of the enzymes that produce reactive oxygen species, decreased activity of antioxidant enzymes and imbalances in glutathione pools mediate and mark the neurodegenerative process. Much of the oxidative damage of proteins is brought about by the overproduction of nitric oxide by nitric oxide synthases (NOS) and its subsequent reactivity with reactive oxygen species. Proteomic methods have advanced the field tremendously, by facilitating the quantitative assessment of differential expression patterns and oxidative modifications of proteins and alongside, mapping their non-canonical functions. As a signaling molecule involved in multiple biochemical pathways, the level of nitric oxide is subject to tight regulation. All three NOS isoforms display aberrant patterns of expression in Alzheimer's disease, altering intracellular signaling and routing oxidative stress in directions that are uncompounded. This review discusses the prime factors that control nitric oxide biosynthesis, reactivity footprints and ensuing effects in the development of neurodegenerative diseases.

  12. Structural kinetic modeling of metabolic networks.

    PubMed

    Steuer, Ralf; Gross, Thilo; Selbig, Joachim; Blasius, Bernd

    2006-08-08

    To develop and investigate detailed mathematical models of metabolic processes is one of the primary challenges in systems biology. However, despite considerable advance in the topological analysis of metabolic networks, kinetic modeling is still often severely hampered by inadequate knowledge of the enzyme-kinetic rate laws and their associated parameter values. Here we propose a method that aims to give a quantitative account of the dynamical capabilities of a metabolic system, without requiring any explicit information about the functional form of the rate equations. Our approach is based on constructing a local linear model at each point in parameter space, such that each element of the model is either directly experimentally accessible or amenable to a straightforward biochemical interpretation. This ensemble of local linear models, encompassing all possible explicit kinetic models, then allows for a statistical exploration of the comprehensive parameter space. The method is exemplified on two paradigmatic metabolic systems: the glycolytic pathway of yeast and a realistic-scale representation of the photosynthetic Calvin cycle.

  13. Pretreatment of lignocellulose: Formation of inhibitory by-products and strategies for minimizing their effects.

    PubMed

    Jönsson, Leif J; Martín, Carlos

    2016-01-01

    Biochemical conversion of lignocellulosic feedstocks to advanced biofuels and other commodities through a sugar-platform process involves a pretreatment step enhancing the susceptibility of the cellulose to enzymatic hydrolysis. A side effect of pretreatment is formation of lignocellulose-derived by-products that inhibit microbial and enzymatic biocatalysts. This review provides an overview of the formation of inhibitory by-products from lignocellulosic feedstocks as a consequence of using different pretreatment methods and feedstocks as well as an overview of different strategies used to alleviate problems with inhibitors. As technologies for biorefining of lignocellulose become mature and are transferred from laboratory environments to industrial contexts, the importance of management of inhibition problems is envisaged to increase as issues that become increasingly relevant will include the possibility to use recalcitrant feedstocks, obtaining high product yields and high productivity, minimizing the charges of enzymes and microorganisms, and using high solids loadings to obtain high product titers. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Microfluidic devices for cell cultivation and proliferation

    PubMed Central

    Tehranirokh, Masoomeh; Kouzani, Abbas Z.; Francis, Paul S.; Kanwar, Jagat R.

    2013-01-01

    Microfluidic technology provides precise, controlled-environment, cost-effective, compact, integrated, and high-throughput microsystems that are promising substitutes for conventional biological laboratory methods. In recent years, microfluidic cell culture devices have been used for applications such as tissue engineering, diagnostics, drug screening, immunology, cancer studies, stem cell proliferation and differentiation, and neurite guidance. Microfluidic technology allows dynamic cell culture in microperfusion systems to deliver continuous nutrient supplies for long term cell culture. It offers many opportunities to mimic the cell-cell and cell-extracellular matrix interactions of tissues by creating gradient concentrations of biochemical signals such as growth factors, chemokines, and hormones. Other applications of cell cultivation in microfluidic systems include high resolution cell patterning on a modified substrate with adhesive patterns and the reconstruction of complicated tissue architectures. In this review, recent advances in microfluidic platforms for cell culturing and proliferation, for both simple monolayer (2D) cell seeding processes and 3D configurations as accurate models of in vivo conditions, are examined. PMID:24273628

  15. Lysophosphatidic acid as a lipid mediator with multiple biological actions.

    PubMed

    Aikawa, Shizu; Hashimoto, Takafumi; Kano, Kuniyuki; Aoki, Junken

    2015-02-01

    Lysophosphatidic acid (LPA) is one of the simplest glycerophospholipids with one fatty acid chain and a phosphate group as a polar head. Although LPA had been viewed just as a metabolic intermediate in de novo lipid synthetic pathways, it has recently been paid much attention as a lipid mediator. LPA exerts many kinds of cellular processes, such as cell proliferation and smooth muscle contraction, through cognate G protein-coupled receptors. Because lipids are not coded by the genome directly, it is difficult to know their patho- and physiological roles. However, recent studies have identified several key factors mediating the biological roles of LPA, such as receptors and producing enzymes. In addition, studies of transgenic and gene knockout animals for these LPA-related genes, have revealed the biological significance of LPA. In this review we will summarize recent advances in the studies of LPA production and its roles in both physiological and pathological conditions. © The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  16. Use of multidimensional, multimodal imaging and PACS to support neurological diagnoses

    NASA Astrophysics Data System (ADS)

    Wong, Stephen T. C.; Knowlton, Robert C.; Hoo, Kent S.; Huang, H. K.

    1995-05-01

    Technological advances in brain imaging have revolutionized diagnosis in neurology and neurological surgery. Major imaging techniques include magnetic resonance imaging (MRI) to visualize structural anatomy, positron emission tomography (PET) to image metabolic function and cerebral blood flow, magnetoencephalography (MEG) to visualize the location of physiologic current sources, and magnetic resonance spectroscopy (MRS) to measure specific biochemicals. Each of these techniques studies different biomedical aspects of the brain, but there lacks an effective means to quantify and correlate the disparate imaging datasets in order to improve clinical decision making processes. This paper describes several techniques developed in a UNIX-based neurodiagnostic workstation to aid the noninvasive presurgical evaluation of epilepsy patients. These techniques include online access to the picture archiving and communication systems (PACS) multimedia archive, coregistration of multimodality image datasets, and correlation and quantitation of structural and functional information contained in the registered images. For illustration, we describe the use of these techniques in a patient case of nonlesional neocortical epilepsy. We also present out future work based on preliminary studies.

  17. The importance of ATP-related compounds for the freshness and flavor of post-mortem fish and shellfish muscle: A review.

    PubMed

    Hong, Hui; Regenstein, Joe M; Luo, Yongkang

    2017-06-13

    ATP degradation is one of the most important biochemical changes in the post-mortem muscle of fish and shellfish. This process has long been recognized as an accurate way to evaluate freshness of fish and shellfish product. This review updates and condenses the overall history and recent advances in understanding the role of ATP-related compounds in post-mortem fish and shellfish muscle including a discussion of key analytical methods, their use as a freshness indicator, their roles in flavor enhancement, the factors affecting their transitions, and the possible mechanisms responsible for their impact on flavor and freshness. Moreover, some challenges and future directions for research regarding ATP-related compounds in fish and shellfish flavor and freshness are presented. With increasing consumer demands for fresh products with extended shelf life, understanding the relationships between ATP-related compounds and their involvement in the freshness and umami taste is a prerequisite for assuring the high quality of fish and shellfish.

  18. Advantages in functional imaging of the brain.

    PubMed

    Mier, Walter; Mier, Daniela

    2015-01-01

    As neuronal pathologies cause only minor morphological alterations, molecular imaging techniques are a prerequisite for the study of diseases of the brain. The development of molecular probes that specifically bind biochemical markers and the advances of instrumentation have revolutionized the possibilities to gain insight into the human brain organization and beyond this-visualize structure-function and brain-behavior relationships. The review describes the development and current applications of functional brain imaging techniques with a focus on applications in psychiatry. A historical overview of the development of functional imaging is followed by the portrayal of the principles and applications of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), two key molecular imaging techniques that have revolutionized the ability to image molecular processes in the brain. We conclude that the juxtaposition of PET and fMRI in hybrid PET/MRI scanners enhances the significance of both modalities for research in neurology and psychiatry and might pave the way for a new area of personalized medicine.

  19. Advanced concepts in biomass production and pretreatment. Annual report, April 1986-March 1987

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

    Hiler, E.A.; Miller, F.R.; Dominy, R.E.

    1987-04-01

    The objective of the research is to develop an integrated system for methane production utilizing terrestrial biomass as the feedstock. The report provides specifics of research activities in the Texas A and M biomass program sponsored by Gas Research Institute and co-funded by Texas Agricultural Experiment Station. Researchers in the program include plant geneticists, plant physiologists, chemists, agronomists, ruminant physiologists, agricultural engineers, biochemical engineers, and agricultural economists. Major research emphases are genetic manipulation, physiology and production systems, harvesting, storage, processing and conversion systems, inhibitors, and economic and system analyses. During the past year, increasing emphasis was placed on the biologicalmore » pretreatment aspects of the program because of the critical importance of the area to the improved efficiency of the overall system. In the breeding, tissue culture, and production programs, continued substantial progress was made in identifying and characterizing sorghums that will produce high biomass yields and have improved lodging resistance and high uniformity. Economic and systems analyses provided important information regarding optimal overall systems.« less

  20. Automated Microbial Metabolism Laboratory

    NASA Technical Reports Server (NTRS)

    1973-01-01

    Development of the automated microbial metabolism laboratory (AMML) concept is reported. The focus of effort of AMML was on the advanced labeled release experiment. Labeled substrates, inhibitors, and temperatures were investigated to establish a comparative biochemical profile. Profiles at three time intervals on soil and pure cultures of bacteria isolated from soil were prepared to establish a complete library. The development of a strategy for the return of a soil sample from Mars is also reported.

  1. Synthetic (polymer) biology (membrane): functionalization of polymer scaffolds for membrane proteins.

    PubMed

    Hu, Zhaolong; Ho, James C S; Nallani, Madhavan

    2017-08-01

    A plethora of polymer-based scaffolds have been designed to facilitate biochemical and biophysical investigation of membrane proteins, with a common goal to stabilize and present them in a functional format. In this review, an up-to-date account of such polymer-based supports and incorporation methodologies are presented. Furthermore, conceptual and imminent technological advances, with associated technical challenges are proposed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Overview of a workshop to expand the use of emerging technology to understand the ecology of grouse in a changing climate

    Treesearch

    Jennifer Forbey; Gail Patricelli; Donna Delparte; Alan Krakauer; Peter Olsoy; Marcella Fremgen; Jordan Nobler; Nancy Glenn; Lucas Spaete; Bryce Richardson; Lisa Shipley; Jessica Mitchell

    2016-01-01

    We held a workshop related to the use of emerging technology to understand the ecology of grouse on 03 September 2015 from 08:00 to 17:30 at the Reykjavik Family Park and Zoo, Reykjavik, Iceland as part of the 13th International Grouse Symposium. Our overall objective was to translate technological advances in remote sensing, rapid biochemical assays, and robotics to...

  3. Modelling and analysis of the sugar cataract development process using stochastic hybrid systems.

    PubMed

    Riley, D; Koutsoukos, X; Riley, K

    2009-05-01

    Modelling and analysis of biochemical systems such as sugar cataract development (SCD) are critical because they can provide new insights into systems, which cannot be easily tested with experiments; however, they are challenging problems due to the highly coupled chemical reactions that are involved. The authors present a stochastic hybrid system (SHS) framework for modelling biochemical systems and demonstrate the approach for the SCD process. A novel feature of the framework is that it allows modelling the effect of drug treatment on the system dynamics. The authors validate the three sugar cataract models by comparing trajectories computed by two simulation algorithms. Further, the authors present a probabilistic verification method for computing the probability of sugar cataract formation for different chemical concentrations using safety and reachability analysis methods for SHSs. The verification method employs dynamic programming based on a discretisation of the state space and therefore suffers from the curse of dimensionality. To analyse the SCD process, a parallel dynamic programming implementation that can handle large, realistic systems was developed. Although scalability is a limiting factor, this work demonstrates that the proposed method is feasible for realistic biochemical systems.

  4. Production of giant mouse oocyte nucleoli and assessment of their protein content.

    PubMed

    Fulka, Helena; Martinkova, Stanislava; Kyogoku, Hirohisa; Langerova, Alena; Fulka, Josef

    2012-01-01

    Compared with advanced developmental stage embryos and somatic cells, fully grown mammalian oocytes contain specific nucleolus-like structures (NPB - nucleolus precursor bodies). It is commonly accepted that they serve as a store of material(s) from which typical nucleoli are gradually formed. Whilst nucleoli from somatic cells can be collected relatively easily for further biochemical analyses, a sufficient number of oocyte nucleoli is very difficult to obtain. We have found that isolated oocytes nucleoli fuse very efficiently when contact is established between them. Thus, well visible giant nucleoli can be obtained, relatively easily handled and then used for further biochemical analyses. With the use of colloidal gold staining, we estimated that a single fully grown mouse oocyte nucleolus contains approximately 1.6 ng of protein. We do believe that this approach will accelerate further research aiming at analyzing the composition of oocyte nucleoli in more detail.

  5. Common folds and transport mechanisms of secondary active transporters.

    PubMed

    Shi, Yigong

    2013-01-01

    Secondary active transporters exploit the electrochemical potential of solutes to shuttle specific substrate molecules across biological membranes, usually against their concentration gradient. Transporters of different functional families with little sequence similarity have repeatedly been found to exhibit similar folds, exemplified by the MFS, LeuT, and NhaA folds. Observations of multiple conformational states of the same transporter, represented by the LeuT superfamily members Mhp1, AdiC, vSGLT, and LeuT, led to proposals that structural changes are associated with substrate binding and transport. Despite recent biochemical and structural advances, our understanding of substrate recognition and energy coupling is rather preliminary. This review focuses on the common folds and shared transport mechanisms of secondary active transporters. Available structural information generally supports the alternating access model for substrate transport, with variations and extensions made by emerging structural, biochemical, and computational evidence.

  6. The secret life of kinases: insights into non-catalytic signalling functions from pseudokinases.

    PubMed

    Jacobsen, Annette V; Murphy, James M

    2017-06-15

    Over the past decade, our understanding of the mechanisms by which pseudokinases, which comprise ∼10% of the human and mouse kinomes, mediate signal transduction has advanced rapidly with increasing structural, biochemical, cellular and genetic studies. Pseudokinases are the catalytically defective counterparts of conventional, active protein kinases and have been attributed functions as protein interaction domains acting variously as allosteric modulators of conventional protein kinases and other enzymes, as regulators of protein trafficking or localisation, as hubs to nucleate assembly of signalling complexes, and as transmembrane effectors of such functions. Here, by categorising mammalian pseudokinases based on their known functions, we illustrate the mechanistic diversity among these proteins, which can be viewed as a window into understanding the non-catalytic functions that can be exerted by conventional protein kinases. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  7. A generic, cost-effective, and scalable cell lineage analysis platform

    PubMed Central

    Biezuner, Tamir; Spiro, Adam; Raz, Ofir; Amir, Shiran; Milo, Lilach; Adar, Rivka; Chapal-Ilani, Noa; Berman, Veronika; Fried, Yael; Ainbinder, Elena; Cohen, Galit; Barr, Haim M.; Halaban, Ruth; Shapiro, Ehud

    2016-01-01

    Advances in single-cell genomics enable commensurate improvements in methods for uncovering lineage relations among individual cells. Current sequencing-based methods for cell lineage analysis depend on low-resolution bulk analysis or rely on extensive single-cell sequencing, which is not scalable and could be biased by functional dependencies. Here we show an integrated biochemical-computational platform for generic single-cell lineage analysis that is retrospective, cost-effective, and scalable. It consists of a biochemical-computational pipeline that inputs individual cells, produces targeted single-cell sequencing data, and uses it to generate a lineage tree of the input cells. We validated the platform by applying it to cells sampled from an ex vivo grown tree and analyzed its feasibility landscape by computer simulations. We conclude that the platform may serve as a generic tool for lineage analysis and thus pave the way toward large-scale human cell lineage discovery. PMID:27558250

  8. MreB: pilot or passenger of cell wall synthesis?

    PubMed

    White, Courtney L; Gober, James W

    2012-02-01

    The discovery that the bacterial cell shape determinant MreB is related to actin spurred new insights into bacterial morphogenesis and development. The trafficking and mechanical roles of the eukaryotic cytoskeleton were hypothesized to have a functional ancestor in MreB based on evidence implicating MreB as an organizer of cell wall synthesis. Genetic, biochemical and cytological studies implicate MreB as a coordinator of a large multi-protein peptidoglycan (PG) synthesizing holoenzyme. Recent advances in microscopy and new biochemical evidence, however, suggest that MreB may function differently than previously envisioned. This review summarizes our evolving knowledge of MreB and attempts to refine the generalized model of the proteins organizing PG synthesis in bacteria. This is generally thought to be conserved among eubacteria and the majority of the discussion will focus on studies from a few well-studied model organisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Multidrug efflux pumps: the structures of prokaryotic ATP-binding cassette transporter efflux pumps and implications for our understanding of eukaryotic P-glycoproteins and homologues.

    PubMed

    Kerr, Ian D; Jones, Peter M; George, Anthony M

    2010-02-01

    One of the Holy Grails of ATP-binding cassette transporter research is a structural understanding of drug binding and transport in a eukaryotic multidrug resistance pump. These transporters are front-line mediators of drug resistance in cancers and represent an important therapeutic target in future chemotherapy. Although there has been intensive biochemical research into the human multidrug pumps, their 3D structure at atomic resolution remains unknown. The recent determination of the structure of a mouse P-glycoprotein at subatomic resolution is complemented by structures for a number of prokaryotic homologues. These structures have provided advances into our knowledge of the ATP-binding cassette exporter structure and mechanism, and have provided the template data for a number of homology modelling studies designed to reconcile biochemical data on these clinically important proteins.

  10. A review on bio-electrochemical systems (BESs) for the syngas and value added biochemicals production.

    PubMed

    Kumar, Gopalakrishnan; Saratale, Rijuta Ganesh; Kadier, Abudukeremu; Sivagurunathan, Periyasamy; Zhen, Guangyin; Kim, Sang-Hyoun; Saratale, Ganesh Dattatraya

    2017-06-01

    Bio-electrochemical systems (BESs) are the microbial systems which are employed to produce electricity directly from organic wastes along with some valuable chemicals production such as medium chain fatty acids; acetate, butyrate and alcohols. In this review, recent updates about value-added chemicals production concomitantly with the production of gaseous fuels like hydrogen and methane which are considered as cleaner for the environment have been addressed. Additionally, the bottlenecks associated with the conversion rates, lower yields and other aspects have been mentioned. In spite of its infant stage development, this would be the future trend of energy, biochemicals and electricity production in greener and cleaner pathway with the win-win situation of organic waste remediation. Henceforth, this review intends to summarise and foster the progress made in the BESs and discusses its challenges and outlook on future research advances. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Biochemical Profile of Heritage and Modern Apple Cultivars and Application of Machine Learning Methods To Predict Usage, Age, and Harvest Season.

    PubMed

    Anastasiadi, Maria; Mohareb, Fady; Redfern, Sally P; Berry, Mark; Simmonds, Monique S J; Terry, Leon A

    2017-07-05

    The present study represents the first major attempt to characterize the biochemical profile in different tissues of a large selection of apple cultivars sourced from the United Kingdom's National Fruit Collection comprising dessert, ornamental, cider, and culinary apples. Furthermore, advanced machine learning methods were applied with the objective to identify whether the phenolic and sugar composition of an apple cultivar could be used as a biomarker fingerprint to differentiate between heritage and mainstream commercial cultivars as well as govern the separation among primary usage groups and harvest season. A prediction accuracy of >90% was achieved with the random forest method for all three models. The results highlighted the extraordinary phytochemical potency and unique profile of some heritage, cider, and ornamental apple cultivars, especially in comparison to more mainstream apple cultivars. Therefore, these findings could guide future cultivar selection on the basis of health-promoting phytochemical content.

  12. Current Opportunities for Clinical Monitoring of Axonal Pathology in Traumatic Brain Injury

    PubMed Central

    Tsitsopoulos, Parmenion P.; Abu Hamdeh, Sami; Marklund, Niklas

    2017-01-01

    Traumatic brain injury (TBI) is a multidimensional and highly complex disease commonly resulting in widespread injury to axons, due to rapid inertial acceleration/deceleration forces transmitted to the brain during impact. Axonal injury leads to brain network dysfunction, significantly contributing to cognitive and functional impairments frequently observed in TBI survivors. Diffuse axonal injury (DAI) is a clinical entity suggested by impaired level of consciousness and coma on clinical examination and characterized by widespread injury to the hemispheric white matter tracts, the corpus callosum and the brain stem. The clinical course of DAI is commonly unpredictable and it remains a challenging entity with limited therapeutic options, to date. Although axonal integrity may be disrupted at impact, the majority of axonal pathology evolves over time, resulting from delayed activation of complex intracellular biochemical cascades. Activation of these secondary biochemical pathways may lead to axonal transection, named secondary axotomy, and be responsible for the clinical decline of DAI patients. Advances in the neurocritical care of TBI patients have been achieved by refinements in multimodality monitoring for prevention and early detection of secondary injury factors, which can be applied also to DAI. There is an emerging role for biomarkers in blood, cerebrospinal fluid, and interstitial fluid using microdialysis in the evaluation of axonal injury in TBI. These biomarker studies have assessed various axonal and neuroglial markers as well as inflammatory mediators, such as cytokines and chemokines. Moreover, modern neuroimaging can detect subtle or overt DAI/white matter changes in diffuse TBI patients across all injury severities using magnetic resonance spectroscopy, diffusion tensor imaging, and positron emission tomography. Importantly, serial neuroimaging studies provide evidence for evolving axonal injury. Since axonal injury may be a key risk factor for neurodegeneration and dementias at long-term following TBI, the secondary injury processes may require prolonged monitoring. The aim of the present review is to summarize the clinical short- and long-term monitoring possibilities of axonal injury in TBI. Increased knowledge of the underlying pathophysiology achieved by advanced clinical monitoring raises hope for the development of novel treatment strategies for axonal injury in TBI. PMID:29209266

  13. A thermochemical-biochemical hybrid processing of lignocellulosic biomass for producing fuels and chemicals.

    PubMed

    Shen, Yanwen; Jarboe, Laura; Brown, Robert; Wen, Zhiyou

    2015-12-01

    Thermochemical-biological hybrid processing uses thermochemical decomposition of lignocellulosic biomass to produce a variety of intermediate compounds that can be converted into fuels and chemicals through microbial fermentation. It represents a unique opportunity for biomass conversion as it mitigates some of the deficiencies of conventional biochemical (pretreatment-hydrolysis-fermentation) and thermochemical (pyrolysis or gasification) processing. Thermochemical-biological hybrid processing includes two pathways: (i) pyrolysis/pyrolytic substrate fermentation, and (ii) gasification/syngas fermentation. This paper provides a comprehensive review of these two hybrid processing pathways, including the characteristics of fermentative substrates produced in the thermochemical stage and microbial utilization of these compounds in the fermentation stage. The current challenges of these two biomass conversion pathways include toxicity of the crude pyrolytic substrates, the inhibition of raw syngas contaminants, and the mass-transfer limitations in syngas fermentation. Possible approaches for mitigating substrate toxicities are discussed. The review also provides a summary of the current efforts to commercialize hybrid processing. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Cell biology and molecular basis of denitrification.

    PubMed Central

    Zumft, W G

    1997-01-01

    Denitrification is a distinct means of energy conservation, making use of N oxides as terminal electron acceptors for cellular bioenergetics under anaerobic, microaerophilic, and occasionally aerobic conditions. The process is an essential branch of the global N cycle, reversing dinitrogen fixation, and is associated with chemolithotrophic, phototrophic, diazotrophic, or organotrophic metabolism but generally not with obligately anaerobic life. Discovered more than a century ago and believed to be exclusively a bacterial trait, denitrification has now been found in halophilic and hyperthermophilic archaea and in the mitochondria of fungi, raising evolutionarily intriguing vistas. Important advances in the biochemical characterization of denitrification and the underlying genetics have been achieved with Pseudomonas stutzeri, Pseudomonas aeruginosa, Paracoccus denitrificans, Ralstonia eutropha, and Rhodobacter sphaeroides. Pseudomonads represent one of the largest assemblies of the denitrifying bacteria within a single genus, favoring their use as model organisms. Around 50 genes are required within a single bacterium to encode the core structures of the denitrification apparatus. Much of the denitrification process of gram-negative bacteria has been found confined to the periplasm, whereas the topology and enzymology of the gram-positive bacteria are less well established. The activation and enzymatic transformation of N oxides is based on the redox chemistry of Fe, Cu, and Mo. Biochemical breakthroughs have included the X-ray structures of the two types of respiratory nitrite reductases and the isolation of the novel enzymes nitric oxide reductase and nitrous oxide reductase, as well as their structural characterization by indirect spectroscopic means. This revealed unexpected relationships among denitrification enzymes and respiratory oxygen reductases. Denitrification is intimately related to fundamental cellular processes that include primary and secondary transport, protein translocation, cytochrome c biogenesis, anaerobic gene regulation, metalloprotein assembly, and the biosynthesis of the cofactors molybdopterin and heme D1. An important class of regulators for the anaerobic expression of the denitrification apparatus are transcription factors of the greater FNR family. Nitrate and nitric oxide, in addition to being respiratory substrates, have been identified as signaling molecules for the induction of distinct N oxide-metabolizing enzymes. PMID:9409151

  15. Run-length encoding graphic rules, biochemically editable designs and steganographical numeric data embedment for DNA-based cryptographical coding system

    PubMed Central

    Kawano, Tomonori

    2013-01-01

    There have been a wide variety of approaches for handling the pieces of DNA as the “unplugged” tools for digital information storage and processing, including a series of studies applied to the security-related area, such as DNA-based digital barcodes, water marks and cryptography. In the present article, novel designs of artificial genes as the media for storing the digitally compressed data for images are proposed for bio-computing purpose while natural genes principally encode for proteins. Furthermore, the proposed system allows cryptographical application of DNA through biochemically editable designs with capacity for steganographical numeric data embedment. As a model case of image-coding DNA technique application, numerically and biochemically combined protocols are employed for ciphering the given “passwords” and/or secret numbers using DNA sequences. The “passwords” of interest were decomposed into single letters and translated into the font image coded on the separate DNA chains with both the coding regions in which the images are encoded based on the novel run-length encoding rule, and the non-coding regions designed for biochemical editing and the remodeling processes revealing the hidden orientation of letters composing the original “passwords.” The latter processes require the molecular biological tools for digestion and ligation of the fragmented DNA molecules targeting at the polymerase chain reaction-engineered termini of the chains. Lastly, additional protocols for steganographical overwriting of the numeric data of interests over the image-coding DNA are also discussed. PMID:23750303

  16. The B3 Subunit of the Cone Cyclic Nucleotide-gated Channel Regulates the Light Responses of Cones and Contributes to the Channel Structural Flexibility*

    PubMed Central

    Ding, Xi-Qin; Thapa, Arjun; Ma, Hongwei; Xu, Jianhua; Elliott, Michael H.; Rodgers, Karla K.; Smith, Marci L.; Wang, Jin-Shan; Pittler, Steven J.; Kefalov, Vladimir J.

    2016-01-01

    Cone photoreceptor cyclic nucleotide-gated (CNG) channels play a pivotal role in cone phototransduction, which is a process essential for daylight vision, color vision, and visual acuity. Mutations in the cone channel subunits CNGA3 and CNGB3 are associated with human cone diseases, including achromatopsia, cone dystrophies, and early onset macular degeneration. Mutations in CNGB3 alone account for 50% of reported cases of achromatopsia. This work investigated the role of CNGB3 in cone light response and cone channel structural stability. As cones comprise only 2–3% of the total photoreceptor population in the wild-type mouse retina, we used Cngb3−/−/Nrl−/− mice with CNGB3 deficiency on a cone-dominant background in our study. We found that, in the absence of CNGB3, CNGA3 was able to travel to the outer segments, co-localize with cone opsin, and form tetrameric complexes. Electroretinogram analyses revealed reduced cone light response amplitude/sensitivity and slower response recovery in Cngb3−/−/Nrl−/− mice compared with Nrl−/− mice. Absence of CNGB3 expression altered the adaptation capacity of cones and severely compromised function in bright light. Biochemical analysis demonstrated that CNGA3 channels lacking CNGB3 were more resilient to proteolysis than CNGA3/CNGB3 channels, suggesting a hindered structural flexibility. Thus, CNGB3 regulates cone light response kinetics and the channel structural flexibility. This work advances our understanding of the biochemical and functional role of CNGB3 in cone photoreceptors. PMID:26893377

  17. Integrative Utilization of Microenvironments, Biomaterials and Computational Techniques for Advanced Tissue Engineering.

    PubMed

    Shamloo, Amir; Mohammadaliha, Negar; Mohseni, Mina

    2015-10-20

    This review aims to propose the integrative implementation of microfluidic devices, biomaterials, and computational methods that can lead to a significant progress in tissue engineering and regenerative medicine researches. Simultaneous implementation of multiple techniques can be very helpful in addressing biological processes. Providing controllable biochemical and biomechanical cues within artificial extracellular matrix similar to in vivo conditions is crucial in tissue engineering and regenerative medicine researches. Microfluidic devices provide precise spatial and temporal control over cell microenvironment. Moreover, generation of accurate and controllable spatial and temporal gradients of biochemical factors is attainable inside microdevices. Since biomaterials with tunable properties are a worthwhile option to construct artificial extracellular matrix, in vitro platforms that simultaneously utilize natural, synthetic, or engineered biomaterials inside microfluidic devices are phenomenally advantageous to experimental studies in the field of tissue engineering. Additionally, collaboration between experimental and computational methods is a useful way to predict and understand mechanisms responsible for complex biological phenomena. Computational results can be verified by using experimental platforms. Computational methods can also broaden the understanding of the mechanisms behind the biological phenomena observed during experiments. Furthermore, computational methods are powerful tools to optimize the fabrication of microfluidic devices and biomaterials with specific features. Here we present a succinct review of the benefits of microfluidic devices, biomaterial, and computational methods in the case of tissue engineering and regeneration medicine. Furthermore, some breakthroughs in biological phenomena including the neuronal axon development, cancerous cell migration and blood vessel formation via angiogenesis by virtue of the aforementioned approaches are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Brain banks as key part of biochemical and molecular studies on cerebral cortex involvement in Parkinson's disease.

    PubMed

    Ravid, Rivka; Ferrer, Isidro

    2012-04-01

    Exciting developments in basic and clinical neuroscience and recent progress in the field of Parkinson's disease (PD) are partly a result of the availability of human specimens obtained through brain banks. These banks have optimized the methodological, managerial and organizational procedures; standard operating procedures; and ethical, legal and social issues, including the code of conduct for 21st Century brain banking and novel protocols. The present minireview focuses on current brain banking organization and management, as well as the likely future direction of the brain banking field. We emphasize the potentials and pitfalls when using high-quality specimens of the human central nervous system for advancing PD research. PD is a generalized disease in which α-synuclein is not a unique component but, instead, is only one of the players accounting for the complex impairment of biochemical/molecular processes involved in metabolic pathways. This is particularly important in the cerebral cortex, where altered cognition has a complex neurochemical substrate. Mitochondria and energy metabolism impairment, abnormal RNA, microRNA, protein synthesis, post-translational protein modifications and alterations in the lipid composition of membranes and lipid rafts are part of these complementary factors. We have to be alert to the possible pitfalls of each specimen and its suitability for a particular study. Not all samples qualify for the study of DNA, RNA, proteins, post-translational modifications, lipids and metabolomes, although the use of carefully selected samples and appropriate methods minimizes pitfalls and errors and guarantees high-quality reserach. © 2012 The Authors Journal compilation © 2012 FEBS.

  19. Influence of place of residence on indications for genetic amniocentesis in the Pomeranian region of Poland before and after introduction of the Prenatal Screening Program in 2008

    PubMed Central

    Ciach, Katarzyna; Świątkowska-Freund, Małgorzata; Preis, Krzysztof

    2014-01-01

    Background The aim of the study was to analyze differences in the indications for amniocentesis in patients living in urban and rural areas before and after introduction of the Prenatal Screening Program by Polish National Health Insurance agency in the Pomeranian region in 2008. Material/Methods Indications for 2578 amniocenteses performed in the Department of Obstetrics of the Medical University of Gdansk between 1996 and 2010 were recorded. Results Advanced maternal age accounted for 69% of women in urban areas and 61% of women in rural areas being referred for amniocentesis (p<0.001). There was also a significant difference between locations in chromosomal abnormality in previous pregnancy, accounting for 4% of referrals for amniocentesis in urban areas compared with 7% of referrals in rural areas. In urban areas, advanced maternal age accounted for 73% of referrals between 1996–2007 compared with 60% of referrals for amniocentesis between 2008 and 2010 (p=0.004), and in rural areas it was 66% and 54%, respectively (p<0.001). Abnormal result of biochemical screening surprisingly accounted for 13% of referrals for amniocenteses between 1996–2007 in urban areas compared with 28% after 2008 (p<0.001). In rural areas this indication accounted for 12% referrals before 2008 and for 28% from 2008 onward (p<0.001). Conclusions The results of the study suggest that in both urban and rural areas there was a significant decrease in advanced maternal age as a reason for referral for amniocentesis, but a significant increase in abnormal results of biochemical screening as an indication for amniocentesis after 2008. PMID:24785299

  20. Biochemical Process Development and Integration | Bioenergy | NREL

    Science.gov Websites

    Process Development We develop and scale fermentation processes that produce fuels and chemicals from guide experimental designs. Our newly updated fermentation laboratory houses 38 bench-scale fermentors current projects cover the fermentation spectrum including anaerobic, micro-aerobic, aerobic, and gas-to

  1. FATE AND EFFECTS OF PHOSPHORUS ADDITIONS IN SOILS UNDER N2-FIXING RED ALDER

    EPA Science Inventory

    Soil phosphorus (P) dynamics are controlled by the interaction of geochemical, biochemical and biological processes, and changing species composition or management may alter the relative importance of these processes. We examined the role of these processes in two plantations of...

  2. TDPAC and β-NMR applications in chemistry and biochemistry

    NASA Astrophysics Data System (ADS)

    Jancso, Attila; Correia, Joao G.; Gottberg, Alexander; Schell, Juliana; Stachura, Monika; Szunyogh, Dániel; Pallada, Stavroula; Lupascu, Doru C.; Kowalska, Magdalena; Hemmingsen, Lars

    2017-06-01

    Time differential perturbed angular correlation (TDPAC) of γ-rays spectroscopy has been applied in chemistry and biochemistry for decades. Herein we aim to present a comprehensive review of chemical and biochemical applications of TDPAC spectroscopy conducted at ISOLDE over the past 15 years, including elucidation of metal site structure and dynamics in proteins and model systems. β-NMR spectroscopy is well established in nuclear physics, solid state physics, and materials science, but only a limited number of applications in chemistry have appeared. Current endeavors at ISOLDE advancing applications of β-NMR towards chemistry and biochemistry are presented, including the first experiment on 31Mg2+ in an ionic liquid solution. Both techniques require the production of radioisotopes combined with advanced spectroscopic instrumentation present at ISOLDE.

  3. Proteomics of effector-triggered immunity (ETI) in plants.

    PubMed

    Hurley, Brenden; Subramaniam, Rajagopal; Guttman, David S; Desveaux, Darrell

    2014-01-01

    Effector-triggered immunity (ETI) was originally termed gene-for-gene resistance and dates back to fundamental observations of flax resistance to rust fungi by Harold Henry Flor in the 1940s. Since then, genetic and biochemical approaches have defined our current understanding of how plant "resistance" proteins recognize microbial effectors. More recently, proteomic approaches have expanded our view of the protein landscape during ETI and contributed significant advances to our mechanistic understanding of ETI signaling. Here we provide an overview of proteomic techniques that have been used to study plant ETI including both global and targeted approaches. We discuss the challenges associated with ETI proteomics and highlight specific examples from the literature, which demonstrate how proteomics is advancing the ETI research field.

  4. Logic-Based Models for the Analysis of Cell Signaling Networks†

    PubMed Central

    2010-01-01

    Computational models are increasingly used to analyze the operation of complex biochemical networks, including those involved in cell signaling networks. Here we review recent advances in applying logic-based modeling to mammalian cell biology. Logic-based models represent biomolecular networks in a simple and intuitive manner without describing the detailed biochemistry of each interaction. A brief description of several logic-based modeling methods is followed by six case studies that demonstrate biological questions recently addressed using logic-based models and point to potential advances in model formalisms and training procedures that promise to enhance the utility of logic-based methods for studying the relationship between environmental inputs and phenotypic or signaling state outputs of complex signaling networks. PMID:20225868

  5. The case for advanced physics topics in oral and maxillofacial surgery.

    PubMed

    Tandon, Rahul; Herford, Alan S

    2014-10-01

    Research in oral and maxillofacial surgery has focused mainly on principles founded in the biological and chemical sciences, which have provided excellent answers to many questions. However, recent technologic advances have begun to gain prominence in many of the medical sciences, providing clinicians with more effective tools for diagnosis and treatment. The era of modern physics has led to the development of diagnostic techniques that could provide information at a more basic level than many of the current biochemical methods used. The goal of this report is to introduce 2 of these methods and describe how they can be applied to oral and maxillofacial surgery. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  6. [Isolation and identification methods of enterobacteria group and its technological advancement].

    PubMed

    Furuta, Itaru

    2007-08-01

    In the last half-century, isolation and identification methods of enterobacteria groups have markedly improved by technological advancement. Clinical microbiology tests have changed overtime from tube methods to commercial identification kits and automated identification. Tube methods are the original method for the identification of enterobacteria groups, that is, a basically essential method to recognize bacterial fermentation and biochemical principles. In this paper, traditional tube tests are discussed, such as the utilization of carbohydrates, indole, methyl red, and citrate and urease tests. Commercial identification kits and automated instruments by computer based analysis as current methods are also discussed, and those methods provide rapidity and accuracy. Nonculture techniques of nucleic acid typing methods using PCR analysis, and immunochemical methods using monoclonal antibodies can be further developed.

  7. Identifying Opportunities for Vertical Integration of Biochemistry and Clinical Medicine.

    PubMed

    Wendelberger, Karen J.; Burke, Rebecca; Haas, Arthur L.; Harenwattananon, Marisa; Simpson, Deborah

    1998-01-01

    Objectives: Retention of basic science knowledge, as judged by National Board of Medical Examiners' (NBME) data, suffers due to lack of apparent relevance and isolation of instruction from clinical application, especially in biochemistry. However, the literature reveals no systematic process for identifying key biochemical concepts and associated clinical conditions. This study systematically identified difficult biochemical concepts and their common clinical conditions as a critical step towards enhancing relevance and retention of biochemistry.Methods: A multi-step/ multiple stakeholder process was used to: (1) identify important biochemistry concepts; (2) determine students' perceptions of concept difficulty; (3) assess biochemistry faculty, student, and clinical teaching scholars' perceived relevance of identified concepts; and (4) identify associated common clinical conditions for relevant and difficult concepts. Surveys and a modified Delphi process were used to gather data, subsequently analyzed using SPSS for Windows.Results: Sixteen key biochemical concepts were identified. Second year medical students rated 14/16 concepts as extremely difficult while fourth year students rated nine concepts as moderately to extremely difficult. On average, each teaching scholar generated common clinical conditions for 6.2 of the 16 concepts, yielding a set of seven critical concepts and associated clinical conditions.Conclusions: Key stakeholders in the instructional process struggle to identify biochemistry concepts that are critical, difficult to learn and associated with common clinical conditions. However, through a systematic process beginning with identification of concepts and associated clinical conditions, relevance of basic science instruction can be enhanced.

  8. The renaissance of lipoprotein(a): Brave new world for preventive cardiology?

    PubMed

    Ellis, Katrina L; Boffa, Michael B; Sahebkar, Amirhossein; Koschinsky, Marlys L; Watts, Gerald F

    2017-10-01

    Lipoprotein(a) [Lp(a)] is a highly heritable cardiovascular risk factor. Although discovered more than 50 years ago, Lp(a) has recently re-emerged as a major focus in the fields of lipidology and preventive cardiology owing to findings from genetic studies and the possibility of lowering elevated plasma concentrations with new antisense therapy. Data from genetic, epidemiological and clinical studies have provided compelling evidence establishing Lp(a) as a causal risk factor for atherosclerotic cardiovascular disease. Nevertheless, major gaps in knowledge remain and the identification of the mechanistic processes governing both Lp(a) pathobiology and metabolism are an ongoing challenge. Furthermore, the complex structure of Lp(a) presents a major obstacle to the accurate quantification of plasma concentrations, and a universally accepted and standardized approach for measuring Lp(a) is required. Significant progress has been made in the development of novel therapeutics for selectively lowering Lp(a). However, before these therapies can be widely implemented further investigations are required to assess their efficacy, safety, and cost-efficiency in the prevention of cardiovascular events. We review recent advances in molecular and biochemical aspects, epidemiology, and pathobiology of Lp(a), and provide a contemporary update on the significance of Lp(a) in clinical medicine. "Progress lies not in enhancing what is, but in advancing toward what will be." (Khalil Gibran). Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Economic feasibility of biochemical processes for the upgrading of crudes and the removal of sulfur, nitrogen, and trace metals from crude oil -- Benchmark cost establishment of biochemical processes on the basis of conventional downstream technologies. Final report FY95

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

    Premuzic, E.T.

    1996-08-01

    During the past several years, a considerable amount of work has been carried out showing that microbially enhanced oil recovery (MEOR) is promising and the resulting biotechnology may be deliverable. At Brookhaven National Laboratory (BNL), systematic studies have been conducted which dealt with the effects of thermophilic and thermoadapted bacteria on the chemical and physical properties of selected types of crude oils at elevated temperatures and pressures. Current studies indicate that during the biotreatment several chemical and physical properties of crude oils are affected. The oils are (1) emulsified; (2) acidified; (3) there is a qualitative and quantitative change inmore » light and heavy fractions of the crudes; (4) there are chemical changes in fractions containing sulfur compounds; (5) there is an apparent reduction in the concentration of trace metals; and (6) the qualitative and quantitative changes appear to be microbial species dependent; and (7) there is a distinction between biodegraded and biotreated oils. The downstream biotechnological crude oil processing research performed thus far is of laboratory scale and has focused on demonstrating the technical feasibility of downstream processing with different types of biocatalysts under a variety of processing conditions. Quantitative economic analysis is the topic of the present project which investigates the economic feasibility of the various biochemical downstream processes which hold promise in upgrading of heavy crudes, such as those found in California, e.g., Monterey-type, Midway Sunset, Honda crudes, and others.« less

  10. Biochemical marker reference values across pediatric, adult, and geriatric ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian Health Measures Survey.

    PubMed

    Adeli, Khosrow; Higgins, Victoria; Nieuwesteeg, Michelle; Raizman, Joshua E; Chen, Yunqi; Wong, Suzy L; Blais, David

    2015-08-01

    Biological covariates such as age and sex can markedly influence biochemical marker reference values, but no comprehensive study has examined such changes across pediatric, adult, and geriatric ages. The Canadian Health Measures Survey (CHMS) collected comprehensive nationwide health information and blood samples from children and adults in the household population and, in collaboration with the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER), examined biological changes in biochemical markers from pediatric to geriatric age, establishing a comprehensive reference interval database for routine disease biomarkers. The CHMS collected health information, physical measurements, and biosamples (blood and urine) from approximately 12 000 Canadians aged 3-79 years and measured 24 biochemical markers with the Ortho Vitros 5600 FS analyzer or a manual microplate. By use of CLSI C28-A3 guidelines, we determined age- and sex-specific reference intervals, including corresponding 90% CIs, on the basis of specific exclusion criteria. Biochemical marker reference values exhibited dynamic changes from pediatric to geriatric age. Most biochemical markers required some combination of age and/or sex partitioning. Two or more age partitions were required for all analytes except bicarbonate, which remained constant throughout life. Additional sex partitioning was required for most biomarkers, except bicarbonate, total cholesterol, total protein, urine iodine, and potassium. Understanding the fluctuations in biochemical markers over a wide age range provides important insight into biological processes and facilitates clinical application of biochemical markers to monitor manifestation of various disease states. The CHMS-CALIPER collaboration addresses this important evidence gap and allows the establishment of robust pediatric and adult reference intervals. © 2015 American Association for Clinical Chemistry.

  11. Good laboratory practices for biochemical genetic testing and newborn screening for inherited metabolic disorders.

    PubMed

    2012-04-06

    Biochemical genetic testing and newborn screening are essential laboratory services for the screening, detection, diagnosis, and monitoring of inborn errors of metabolism or inherited metabolic disorders. Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations, laboratory testing is categorized on the basis of the level of testing complexity as either waived (i.e., from routine regulatory oversight) or nonwaived testing (which includes tests of moderate and high complexity). Laboratories that perform biochemical genetic testing are required by CLIA regulations to meet the general quality systems requirements for nonwaived testing and the personnel requirements for high-complexity testing. Laboratories that perform public health newborn screening are subject to the same CLIA regulations and applicable state requirements. As the number of inherited metabolic diseases that are included in state-based newborn screening programs continues to increase, ensuring the quality of performance and delivery of testing services remains a continuous challenge not only for public health laboratories and other newborn screening facilities but also for biochemical genetic testing laboratories. To help ensure the quality of laboratory testing, CDC collaborated with the Centers for Medicare & Medicaid Services, the Food and Drug Administration, the Health Resources and Services Administration, and the National Institutes of Health to develop guidelines for laboratories to meet CLIA requirements and apply additional quality assurance measures for these areas of genetic testing. This report provides recommendations for good laboratory practices that were developed based on recommendations from the Clinical Laboratory Improvement Advisory Committee, with additional input from the Secretary's Advisory Committee on Genetics, Health, and Society; the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; and representatives of newborn screening laboratories. The recommended practices address the benefits of using a quality management system approach, factors to consider before introducing new tests, establishment and verification of test performance specifications, the total laboratory testing process (which consists of the preanalytic, analytic, and postanalytic phases), confidentiality of patient information and test results, and personnel qualifications and responsibilities for laboratory testing for inherited metabolic diseases. These recommendations are intended for laboratories that perform biochemical genetic testing to improve the quality of laboratory services and for newborn screening laboratories to ensure the quality of laboratory practices for inherited metabolic disorders. These recommendations also are intended as a resource for medical and public health professionals who evaluate laboratory practices, for users of laboratory services to facilitate their collaboration with newborn screening systems and use of biochemical genetic tests, and for standard-setting organizations and professional societies in developing future laboratory quality standards and practice recommendations. This report complements Good Laboratory Practices for Molecular Genetic Testing for Heritable Diseases and Conditions (CDC. Good laboratory practices for molecular genetic testing for heritable diseases and conditions. MMWR 2009;58 [No. RR-6]) to provide guidance for ensuring and improving the quality of genetic laboratory services and public health outcomes. Future recommendations for additional areas of genetic testing will be considered on the basis of continued monitoring and evaluation of laboratory practices, technology advancements, and the development of laboratory standards and guidelines.

  12. A Critical Examination of the Reaction of Pyridoxal 5-Phosphate with Human Hemoglobin Ao

    DTIC Science & Technology

    1989-01-01

    sodium borohydride gives unacceptable levels of methemoglobin (i.e., > 10%). Excessive foaming and methemoglobin formation can be partially avoided using...a biochemical level . By using new advances in HPLC column technology, we could better determine hetero- geneity in the product mixture due solely to... diphosphoglycerate (2,3-DPG). 6 SFH, which had been stripped of 2,3-DPG, was deoxygenated with nitrogen and treated with a solution of PLP in Tris

  13. Current therapy and drug pipeline for the treatment of patients with acromegaly.

    PubMed

    Kumar, Sampath Satish; Ayuk, John; Murray, Robert D

    2009-04-01

    Acromegaly is a multisystem disease resulting from chronic exposure to supraphysiological levels of growth hormone (GH), and is associated with significant morbidity and excess mortality. The etiology is almost exclusively an underlying pituitary adenoma. Current therapeutic interventions include surgery, radiotherapy, and medical therapy. Despite surgery, around 50% of patients fail to achieve the biochemical targets shown to correlate with normalization of mortality rates. Radiotherapy is efficacious in controlling tumor growth and GH secretion; still, achievement of biochemical targets may take up to a decade and a number of safety issues have been raised with this treatment modality. Medical therapy, therefore, has an important role as adjuvant therapy in patients who fail to achieve control with surgery, or while awaiting the effects of radiotherapy to be realized. Furthermore, medical therapy is increasingly being used as primary therapy. Current medical therapies include dopaminergic agonists, somatostatin analogs, and GH receptor (GHR) antagonists. Dopaminergic agonists achieve biochemical targets in up to 30% of patients, and somatostatin analogs in around 60%. The currently available GHR antagonist pegvisomant effectively controls insulin-like growth factor-I levels in over 90% of patients; however, it has no effect on the tumor itself and has considerable financial implications. Research into optimizing the somatostatin and dopaminergic systems has led to promising advances in agonist development. Moieties with selectivity for various combinations of somatostatin receptor subtype receptors have been examined, along with molecules that additionally show high affinity for the dopaminergic D2 receptor. Of the molecules studied in vitro, only pasireotide (SOM230) and BIM-23A760 are currently undergoing further development. Other innovations to improve convenience of currently available drugs are also being investigated. Significant advances in under standing of the somatostatin and dopaminergic system have aided drug development. This may lead to new clinically available therapies enabling control of acromegaly in a larger proportion of patients, and at an earlier stage in their disease management.

  14. Fluorescent diagnostics of epithelial neoplasms of different colon parts.

    PubMed

    Korneva, Yulia S; Dorosevich, Alexander E; Maryakhina, Valeriya S

    2017-10-01

    Changes in the biochemical composition of the tissue during colon cancer progression usually precede morphological changes registered by light microscopy. These changes are very sensitive and may be used for diagnostics in difficult cases, when it is impossible to obtain sufficient amount of material during colonoscopy. The aim of the study is analysis of spectral characteristics of sporadic adenomas and tumors in different parts of colon for improving tumors diagnostics in disputable cases. The spectra of fluorescence excitation of histological sections from 78 patients with colon cancer (adenocarcinoma) and colonic adenomas of different localizations were measured. The spectra of fluorescence excitation of all types of adenomas as well as adenocarcinoma have two maxima at 260/270 nm and at 330/340 nm. The first maximum is primarily defined by tryptophan and phenylalanin containing peptides, one of them is glucagon. The second maximum is mainly defined by collagen in stroma. Progression of precancer lesions to advanced cancer leads to increase of NADH concentration impacting on the second maximum of spectra. However, spectra of all types of the investigated lesions have peculiarities depending on localization. At odds to the previous data about similarities between distal colon and rectum, our results demonstrate similar spectra for proximal colon and rectum due to some similarities in morphological and, as a consequence, biochemical composition. Tumor can be detected by spectral techniques on histological slides even if the specimen contains very few tumorous cells in stroma. Biochemical changes and their similarities for precancer lesions and advanced colon cancer have described. Peculiarities of spectral data for different parts of colon may change the previous opinion about similar mechanisms of cancerogenesis for distal colon and rectum. Moreover, investigation of tissue specimen obtained for histological examination and containing lack of malignant epithelial cells in massive stroma does not interfere with analysis due to specific disproportion of spectrum maxima. Lasers Surg. Med. 49:763-766, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Biochemical Platform Processing Integration

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

    None

    The objective of this project is to facilitate deployment of enzyme-based biomass conversion technology. The immediate goal is to explore integration issues that impact process performance and to demonstrate improved performance of the lower-cost enzymes being developed by Genencor and Novozymes.

  16. In-vitro synthesis of drug metabolites and their screening/characterization using liquid chromatography-mass spectrometry (LC-MS)

    USDA-ARS?s Scientific Manuscript database

    Drug metabolism is a biochemical process by which drugs and xenobiotics are chemically modified to metabolites, primarily by liver enzymes. Metabolites may sometimes affect cellular therapeutic or toxicological processes, therefore knowledge of metabolic processes is essential for understanding drug...

  17. Modeling oscillations and spiral waves in Dictyostelium populations

    NASA Astrophysics Data System (ADS)

    Noorbakhsh, Javad; Schwab, David J.; Sgro, Allyson E.; Gregor, Thomas; Mehta, Pankaj

    2015-06-01

    Unicellular organisms exhibit elaborate collective behaviors in response to environmental cues. These behaviors are controlled by complex biochemical networks within individual cells and coordinated through cell-to-cell communication. Describing these behaviors requires new mathematical models that can bridge scales—from biochemical networks within individual cells to spatially structured cellular populations. Here we present a family of "multiscale" models for the emergence of spiral waves in the social amoeba Dictyostelium discoideum. Our models exploit new experimental advances that allow for the direct measurement and manipulation of the small signaling molecule cyclic adenosine monophosphate (cAMP) used by Dictyostelium cells to coordinate behavior in cellular populations. Inspired by recent experiments, we model the Dictyostelium signaling network as an excitable system coupled to various preprocessing modules. We use this family of models to study spatially unstructured populations of "fixed" cells by constructing phase diagrams that relate the properties of population-level oscillations to parameters in the underlying biochemical network. We then briefly discuss an extension of our model that includes spatial structure and show how this naturally gives rise to spiral waves. Our models exhibit a wide range of novel phenomena. including a density-dependent frequency change, bistability, and dynamic death due to slow cAMP dynamics. Our modeling approach provides a powerful tool for bridging scales in modeling of Dictyostelium populations.

  18. Biochemical and morphological changes associated with macrophages and osteoclasts when challenged with infection - biomed 2011.

    PubMed

    Wiggers, Erin Callie; Johnson, William; Tucci, Michelle; Benghuzzi, Hamed

    2011-01-01

    Osteomyelitis is a bacterial infection of the bone that occurs frequently as a complication of open fractures and various kinds of orthopedic surgery. This infection can often lead to more extensive surgeries and even death of the patient. In animal models of osteomyelitis, the site of infection by Staphylococcus aureus was observed to have high numbers of both macrophages and osteoclasts, both of which may contribute to large amounts of osteolysis and tissue damage. In order to evaluate the immune response in both types of cells, two cells lines, a macrophage cell line and a macrophage cell line stimulated to become osteoclasts by the addition of receptor activator of nuclear-factor B (RANKL), were exposed to lipopolysaccharides, opsonized S. aureus, and unopsonized S. aureus. The results showed that both cell types activated a biochemical cascade that included the release of cytokines and nitric oxide associated with cell damage and death in response to infection. However, macrophages and osteoclasts differed in response magnitude, most likely due to differences in cell-membrane receptors. This data supports the growing body of research that links the immune and skeletal systems. Further understanding of biochemical pathways shared by the two systems could lead to significant advances in the treatment of osteomyelitis and the success of prostheses.

  19. Characterization of Degenerative Changes in the Temporomandibular Joint of the Bengal Tiger (Panthera tigris tigris) and Siberian Tiger (Panthera tigris altaica)

    PubMed Central

    Murphy, M. K.; Arzi, B.; Vapniarsky-Arzi, N.; Athanasiou, K. A.

    2013-01-01

    Summary The articulation of the temporomandibular joint (TMJ) is composed of the temporal bone dorsally, the mandibular condyle ventrally and a fibrous articular disc. The TMJ disc plays an essential role in distributing load between the two articular surfaces. Degeneration of the disc in the presence of joint pathology has been shown in man; however, TMJ pathology has not been documented previously in tigers (Panthera tigris). The mandibular condyle and TMJ disc of a Bengal tiger (P. tigris tigris) and a Siberian tiger (P. tigris altaica) were evaluated grossly and the TMJ disc was characterized biochemically and mechanically. Characterization of the TMJ disc verified region- and direction-dependent biochemical and mechanical properties, reflective of the functional demands on the joint. Degenerative joint disease was observed in both cases and this was more severe in the Siberian tiger. Simultaneous evaluation of joint pathology, biochemical composition and mechanical properties of the TMJ disc revealed a loss in functional properties (tensile anisotropy) of the disc as joint pathology advanced from moderate to severe. TMJ degeneration may compromise the ability of the animal to eat and thrive and may be a factor contributing to the endangered status of these species. PMID:23809909

  20. A linear spectral matching technique for retrieving equivalent water thickness and biochemical constituents of green vegetation

    NASA Technical Reports Server (NTRS)

    Gao, Bo-Cai; Goetz, Alexander F. H.

    1992-01-01

    Over the last decade, technological advances in airborne imaging spectrometers, having spectral resolution comparable with laboratory spectrometers, have made it possible to estimate biochemical constituents of vegetation canopies. Wessman estimated lignin concentration from data acquired with NASA's Airborne Imaging Spectrometer (AIS) over Blackhawk Island in Wisconsin. A stepwise linear regression technique was used to determine the single spectral channel or channels in the AIS data that best correlated with measured lignin contents using chemical methods. The regression technique does not take advantage of the spectral shape of the lignin reflectance feature as a diagnostic tool nor the increased discrimination among other leaf components with overlapping spectral features. A nonlinear least squares spectral matching technique was recently reported for deriving both the equivalent water thicknesses of surface vegetation and the amounts of water vapor in the atmosphere from contiguous spectra measured with the Airborne Visible/Infrared Imaging Spectrometer (AVIRIS). The same technique was applied to a laboratory reflectance spectrum of fresh, green leaves. The result demonstrates that the fresh leaf spectrum in the 1.0-2.5 microns region consists of spectral components of dry leaves and the spectral component of liquid water. A linear least squares spectral matching technique for retrieving equivalent water thickness and biochemical components of green vegetation is described.

  1. Bacterial Cell Mechanics.

    PubMed

    Auer, George K; Weibel, Douglas B

    2017-07-25

    Cellular mechanical properties play an integral role in bacterial survival and adaptation. Historically, the bacterial cell wall and, in particular, the layer of polymeric material called the peptidoglycan were the elements to which cell mechanics could be primarily attributed. Disrupting the biochemical machinery that assembles the peptidoglycan (e.g., using the β-lactam family of antibiotics) alters the structure of this material, leads to mechanical defects, and results in cell lysis. Decades after the discovery of peptidoglycan-synthesizing enzymes, the mechanisms that underlie their positioning and regulation are still not entirely understood. In addition, recent evidence suggests a diverse group of other biochemical elements influence bacterial cell mechanics, may be regulated by new cellular mechanisms, and may be triggered in different environmental contexts to enable cell adaptation and survival. This review summarizes the contributions that different biomolecular components of the cell wall (e.g., lipopolysaccharides, wall and lipoteichoic acids, lipid bilayers, peptidoglycan, and proteins) make to Gram-negative and Gram-positive bacterial cell mechanics. We discuss the contribution of individual proteins and macromolecular complexes in cell mechanics and the tools that make it possible to quantitatively decipher the biochemical machinery that contributes to bacterial cell mechanics. Advances in this area may provide insight into new biology and influence the development of antibacterial chemotherapies.

  2. Characterization of degenerative changes in the temporomandibular joint of the bengal tiger (Panthera tigris tigris) and siberian tiger (Panthera tigris altaica).

    PubMed

    Murphy, M K; Arzi, B; Vapniarsky-Arzi, N; Athanasiou, K A

    2013-11-01

    The articulation of the temporomandibular joint (TMJ) is composed of the temporal bone dorsally, the mandibular condyle ventrally and a fibrous articular disc. The TMJ disc plays an essential role in distributing load between the two articular surfaces. Degeneration of the disc in the presence of joint pathology has been shown in man; however, TMJ pathology has not been documented previously in tigers (Panthera tigris). The mandibular condyle and TMJ disc of a Bengal tiger (P. tigris tigris) and a Siberian tiger (P. tigris altaica) were evaluated grossly and the TMJ disc was characterized biochemically and mechanically. Characterization of the TMJ disc verified region- and direction-dependent biochemical and mechanical properties, reflective of the functional demands on the joint. Degenerative joint disease was observed in both cases and this was more severe in the Siberian tiger. Simultaneous evaluation of joint pathology, biochemical composition and mechanical properties of the TMJ disc revealed a loss in functional properties (tensile anisotropy) of the disc as joint pathology advanced from moderate to severe. TMJ degeneration may compromise the ability of the animal to eat and thrive and may be a factor contributing to the endangered status of these species. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Fragility of foot process morphology in kidney podocytes arises from chaotic spatial propagation of cytoskeletal instability

    PubMed Central

    Deerinck, Thomas J.; Chen, Yibang; He, John C.; Ellisman, Mark H.; Iyengar, Ravi

    2017-01-01

    Kidney podocytes’ function depends on fingerlike projections (foot processes) that interdigitate with those from neighboring cells to form the glomerular filtration barrier. The integrity of the barrier depends on spatial control of dynamics of actin cytoskeleton in the foot processes. We determined how imbalances in regulation of actin cytoskeletal dynamics could result in pathological morphology. We obtained 3-D electron microscopy images of podocytes and used quantitative features to build dynamical models to investigate how regulation of actin dynamics within foot processes controls local morphology. We find that imbalances in regulation of actin bundling lead to chaotic spatial patterns that could impair the foot process morphology. Simulation results are consistent with experimental observations for cytoskeletal reconfiguration through dysregulated RhoA or Rac1, and they predict compensatory mechanisms for biochemical stability. We conclude that podocyte morphology, optimized for filtration, is intrinsically fragile, whereby local transient biochemical imbalances may lead to permanent morphological changes associated with pathophysiology. PMID:28301477

  4. Differentiation of Staphylococcus aureus from freshly slaughtered poultry and strains 'endemic' to processing plants by biochemical and physiological tests.

    PubMed

    Mead, G C; Norris, A P; Bratchell, N

    1989-02-01

    A comparison was made of 27 'endemic' strains of Staphylococcus aureus and 35 strains from freshly slaughtered birds, isolated at five commercial slaughterhouses processing chickens or turkeys. Of 112 biochemical and physiological tests used, 74 gave results which differed among the strains. Cluster analysis revealed several distinct groupings which were influenced by strain type, processing plant and bird origin; these included a single group at the 72% level of similarity containing most of the 'endemic' strains. In comparison with strains from freshly slaughtered birds, a higher proportion of 'endemic' strains produced fibrinolysin, alpha-glucosidase and urease and were beta-haemolytic on sheep-blood agar. The 'endemic' type also showed a greater tendency to coagulate human but not bovine plasma, and to produce mucoid growth and clumping. The last two properties, relevant to colonization of processing equipment, were less evident in heart infusion broth than in richer media or process water collected during defeathering of the birds.

  5. Techno-economic comparison of biojet fuel production from lignocellulose, vegetable oil and sugar cane juice.

    PubMed

    Diederichs, Gabriel Wilhelm; Ali Mandegari, Mohsen; Farzad, Somayeh; Görgens, Johann F

    2016-09-01

    In this study, a techno-economic comparison was performed considering three processes (thermochemical, biochemical and hybrid) for production of jet fuel from lignocellulosic biomass (2G) versus two processes from first generation (1G) feedstocks, including vegetable oil and sugar cane juice. Mass and energy balances were constructed for energy self-sufficient versions of these processes, not utilising any fossil energy sources, using ASPEN Plus® simulations. All of the investigated processes obtained base minimum jet selling prices (MJSP) that is substantially higher than the market jet fuel price (2-4 fold). The 1G process which converts vegetable oil, obtained the lowest MJSPs of $2.22/kg jet fuel while the two most promising 2G processes- the thermochemical (gasification and Fischer-Tropsch synthesis) and hybrid (gasification and biochemical upgrading) processes- reached MJSPs of $2.44/kg and $2.50/kg jet fuel, respectively. According to the economic sensitivity analysis, the feedstock cost and fixed capital investment have the most influence on the MJSP. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Advanced glycation end-products as markers of aging and longevity in the long-lived Ansell's mole-rat (Fukomys anselli).

    PubMed

    Dammann, Philip; Sell, David R; Begall, Sabine; Strauch, Christopher; Monnier, Vincent M

    2012-06-01

    Mole-rat of the genus Fukomys are mammals whose life span is strongly influenced by reproductive status with breeders far outliving nonbreeders. This raises the important question of whether increased longevity of the breeders is reflected in atypical expression of biochemical markers of aging. Here, we measured markers of glycation and advanced glycation end-products formed in insoluble skin collagen of Ansell's mole-rat Fukomys anselli as a function of age and breeding status. Glucosepane, pentosidine, and total advanced glycation end-product content significantly increased with age after correction for breeder status and sex. Unexpectedly, total advanced glycation end-products, glucosepane, and carboxymethyl-lysine (CML) were significantly higher in breeders versus nonbreeders suggesting that breeders have evolved powerful defenses against combined oxidant and carbonyl stress compared with nonbreeders. Most interestingly, when compared with other mammals, pentosidine formation rate was lower in mole-rat compared with other short-lived rodents confirming previous observations of an inverse relationship between longevity and pentosidine formation rates in skin collagen.

  7. Advanced Glycation End-Products as Markers of Aging and Longevity in the Long-Lived Ansell’s Mole-Rat (Fukomys anselli)

    PubMed Central

    Dammann, Philip; Begall, Sabine; Strauch, Christopher; Monnier, Vincent M.

    2012-01-01

    Mole-rat of the genus Fukomys are mammals whose life span is strongly influenced by reproductive status with breeders far outliving nonbreeders. This raises the important question of whether increased longevity of the breeders is reflected in atypical expression of biochemical markers of aging. Here, we measured markers of glycation and advanced glycation end-products formed in insoluble skin collagen of Ansell’s mole-rat Fukomys anselli as a function of age and breeding status. Glucosepane, pentosidine, and total advanced glycation end-product content significantly increased with age after correction for breeder status and sex. Unexpectedly, total advanced glycation end-products, glucosepane, and carboxymethyl-lysine (CML) were significantly higher in breeders versus nonbreeders suggesting that breeders have evolved powerful defenses against combined oxidant and carbonyl stress compared with nonbreeders. Most interestingly, when compared with other mammals, pentosidine formation rate was lower in mole-rat compared with other short-lived rodents confirming previous observations of an inverse relationship between longevity and pentosidine formation rates in skin collagen. PMID:22156473

  8. Experiences of Australian men diagnosed with advanced prostate cancer: a qualitative study

    PubMed Central

    Chambers, Suzanne K; Hyde, Melissa K; Laurie, Kirstyn; Legg, Melissa; Frydenberg, Mark; Davis, Ian D; Lowe, Anthony; Dunn, Jeff

    2018-01-01

    Objective To explore men’s lived experience of advanced prostate cancer (PCa) and preferences for support. Design Cross-sectional qualitative study applying open-ended surveys and interviews conducted between June and November 2016. Interviews audio-recorded and transcribed verbatim and analysed from an interpretive phenomenological perspective. Setting Australia, nation-wide. Participants 39 men diagnosed with advanced PCa (metastatic or castration-resistant biochemical progression) were surveyed with 28 men subsequently completing a semistructured in depth telephone interview. Results Thematic analysis of interviews identified two organising themes: lived experience and supportive care. Lived experience included six superordinate themes: regret about late diagnosis and treatment decisions, being discounted in the health system, fear/uncertainty about the future, acceptance of their situation, masculinity and treatment effects. Supportive care included five superordinate themes: communication, care coordination, accessible care, shared experience/peer support and involvement of their partner/family. Conclusions Life course and the health and social context of PCa influence men’s experiences of advanced disease. Multimodal interventions integrating peer support and specialist nurses are needed that more closely articulate with men’s expressed needs. PMID:29455168

  9. Examining the architecture of cellular computing through a comparative study with a computer

    PubMed Central

    Wang, Degeng; Gribskov, Michael

    2005-01-01

    The computer and the cell both use information embedded in simple coding, the binary software code and the quadruple genomic code, respectively, to support system operations. A comparative examination of their system architecture as well as their information storage and utilization schemes is performed. On top of the code, both systems display a modular, multi-layered architecture, which, in the case of a computer, arises from human engineering efforts through a combination of hardware implementation and software abstraction. Using the computer as a reference system, a simplistic mapping of the architectural components between the two is easily detected. This comparison also reveals that a cell abolishes the software–hardware barrier through genomic encoding for the constituents of the biochemical network, a cell's ‘hardware’ equivalent to the computer central processing unit (CPU). The information loading (gene expression) process acts as a major determinant of the encoded constituent's abundance, which, in turn, often determines the ‘bandwidth’ of a biochemical pathway. Cellular processes are implemented in biochemical pathways in parallel manners. In a computer, on the other hand, the software provides only instructions and data for the CPU. A process represents just sequentially ordered actions by the CPU and only virtual parallelism can be implemented through CPU time-sharing. Whereas process management in a computer may simply mean job scheduling, coordinating pathway bandwidth through the gene expression machinery represents a major process management scheme in a cell. In summary, a cell can be viewed as a super-parallel computer, which computes through controlled hardware composition. While we have, at best, a very fragmented understanding of cellular operation, we have a thorough understanding of the computer throughout the engineering process. The potential utilization of this knowledge to the benefit of systems biology is discussed. PMID:16849179

  10. Examining the architecture of cellular computing through a comparative study with a computer.

    PubMed

    Wang, Degeng; Gribskov, Michael

    2005-06-22

    The computer and the cell both use information embedded in simple coding, the binary software code and the quadruple genomic code, respectively, to support system operations. A comparative examination of their system architecture as well as their information storage and utilization schemes is performed. On top of the code, both systems display a modular, multi-layered architecture, which, in the case of a computer, arises from human engineering efforts through a combination of hardware implementation and software abstraction. Using the computer as a reference system, a simplistic mapping of the architectural components between the two is easily detected. This comparison also reveals that a cell abolishes the software-hardware barrier through genomic encoding for the constituents of the biochemical network, a cell's "hardware" equivalent to the computer central processing unit (CPU). The information loading (gene expression) process acts as a major determinant of the encoded constituent's abundance, which, in turn, often determines the "bandwidth" of a biochemical pathway. Cellular processes are implemented in biochemical pathways in parallel manners. In a computer, on the other hand, the software provides only instructions and data for the CPU. A process represents just sequentially ordered actions by the CPU and only virtual parallelism can be implemented through CPU time-sharing. Whereas process management in a computer may simply mean job scheduling, coordinating pathway bandwidth through the gene expression machinery represents a major process management scheme in a cell. In summary, a cell can be viewed as a super-parallel computer, which computes through controlled hardware composition. While we have, at best, a very fragmented understanding of cellular operation, we have a thorough understanding of the computer throughout the engineering process. The potential utilization of this knowledge to the benefit of systems biology is discussed.

  11. Biochemical characteristics of a free cyanide and total nitrogen assimilating Fusarium oxysporum EKT01/02 isolate from cyanide contaminated soil.

    PubMed

    Akinpelu, Enoch A; Adetunji, Adewole T; Ntwampe, Seteno K O; Nchu, Felix; Mekuto, Lukhanyo

    2017-10-01

    Sustainability of nutrient requirements for microbial proliferation on a large scale is a challenge in bioremediation processes. This article presents data on biochemical properties of a free cyanide resistant and total nitrogen assimilating fungal isolate from the rhizosphere of Zea mays (maize) growing in soil contaminated with a cyanide-based pesticide. DNA extracted from this isolate were PCR amplified using universal primers; TEF1-α and ITS. The raw sequence files are available on the NCBI database. Characterisation using biochemical data was obtained using colorimetric reagents analysed with VITEK ® 2 software version 7.01. The data will be informative in selection of biocatalyst for environmental engineering application.

  12. Weak Perturbations of Biochemical Oscillators

    NASA Astrophysics Data System (ADS)

    Gailey, Paul

    2001-03-01

    Biochemical oscillators may play important roles in gene regulation, circadian rhythms, physiological signaling, and sensory processes. These oscillations typically occur inside cells where the small numbers of reacting molecules result in fluctuations in the oscillation period. Some oscillation mechanisms have been reported that resist fluctuations and produce more stable oscillations. In this paper, we consider the use of biochemical oscillators as sensors by comparing inherent fluctuations with the effects of weak perturbations to one of the reactants. Such systems could be used to produce graded responses to weak stimuli. For example, a leading hypothesis to explain geomagnetic navigation in migrating birds and other animals is based on magnetochemical reactions. Because the magnitude of magnetochemical effects is small at geomagnetic field strengths, a sensitive, noise resistant detection scheme would be required.

  13. Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules.

    PubMed

    Tikka, Saara; Monogioudi, Evanthia; Gotsopoulos, Athanasios; Soliymani, Rabah; Pezzini, Francesco; Scifo, Enzo; Uusi-Rauva, Kristiina; Tyynelä, Jaana; Baumann, Marc; Jalanko, Anu; Simonati, Alessandro; Lalowski, Maciej

    2016-03-01

    Neuronal ceroid lipofuscinoses (NCL) are the most commonly inherited progressive encephalopathies of childhood. Pathologically, they are characterized by endolysosomal storage with different ultrastructural features and biochemical compositions. The molecular mechanisms causing progressive neurodegeneration and common molecular pathways linking expression of different NCL genes are largely unknown. We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease-palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different stages: pre-symptomatic, symptomatic and advanced. For this purpose, we utilized a combination of laser capture microdissection-based quantitative liquid chromatography tandem mass spectrometry (MS) and matrix-assisted laser desorption/ionization time-of-flight MS imaging to quantify/visualize the changes in protein expression in disease-affected brain thalamus and cerebral cortex tissue slices, respectively. Proteomic profiling of the pre-symptomatic stage thalamus revealed alterations mostly in metabolic processes and inhibition of various neuronal functions, i.e., neuritogenesis. Down-regulation in dynamics associated with growth of plasma projections and cellular protrusions was further corroborated by findings from RNA sequencing of CLN1 patients' fibroblasts. Changes detected at the symptomatic stage included: mitochondrial functions, synaptic vesicle transport, myelin proteome and signaling cascades, such as RhoA signaling. Considerable dysregulation of processes related to mitochondrial cell death, RhoA/Huntington's disease signaling and myelin sheath breakdown were observed at the advanced stage of the disease. The identified changes in protein levels were further substantiated by bioinformatics and network approaches, immunohistochemistry on brain tissues and literature knowledge, thus identifying various functional modules affected in the CLN1 childhood encephalopathy.

  14. Streptomyces sp. is a powerful biotechnological tool for the biodegradation of HCH isomers: biochemical and molecular basis.

    PubMed

    Cuozzo, S A; Sineli, P E; Davila Costa, J; Tortella, G

    2018-08-01

    Actinobacteria are well-known degraders of toxic materials that have the ability to tolerate and remove organochloride pesticides; thus, they are used for bioremediation. The biodegradation of organochlorines by actinobacteria has been demonstrated in pure and mixed cultures with the concomitant production of metabolic intermediates including γ-pentachlorocyclohexene (γ-PCCH); 1,3,4,6-tetrachloro-1,4-cyclohexadiene (1,4-TCDN); 1,2-dichlorobenzene (1,2-DCB), 1,3-dichlorobenzene (1,3-DCB), or 1,4-dichlorobenzene (1,4-DCB); 1,2,3-trichlorobenzene (1,2,3-TCB), 1,2,4-trichlorobenzene (1,2,4-TCB), or 1,3,5-trichlorobenzene (1,3,5-TCB); 1,3-DCB; and 1,2-DCB. Chromatography coupled to mass spectrometric detection, especially GC-MS, is typically used to determine HCH-isomer metabolites. The important enzymes involved in HCH isomer degradation metabolic pathways include hexachlorocyclohexane dehydrochlorinase (LinA), haloalkane dehalogenase (LinB), and alcohol dehydrogenase (LinC). The metabolic versatility of these enzymes is known. Advances have been made in the identification of actinobacterial haloalkane dehydrogenase, which is encoded by linB. This knowledge will permit future improvements in biodegradation processes using Actinobacteria. The enzymatic and genetic characterizations of the molecular mechanisms involved in these processes have not been fully elucidated, necessitating further studies. New advances in this area suggest promising results. The scope of this paper encompasses the following: (i) the aerobic degradation pathways of hexachlorocyclohexane (HCH) isomers; (ii) the important genes and enzymes involved in the metabolic pathways of HCH isomer degradation; and (iii) the identification and quantification of intermediate metabolites through gas chromatography coupled to mass spectrometry (GC-MS).

  15. Barnacle cement: a polymerization model based on evolutionary concepts

    PubMed Central

    Dickinson, Gary H.; Vega, Irving E.; Wahl, Kathryn J.; Orihuela, Beatriz; Beyley, Veronica; Rodriguez, Eva N.; Everett, Richard K.; Bonaventura, Joseph; Rittschof, Daniel

    2009-01-01

    Summary Enzymes and biochemical mechanisms essential to survival are under extreme selective pressure and are highly conserved through evolutionary time. We applied this evolutionary concept to barnacle cement polymerization, a process critical to barnacle fitness that involves aggregation and cross-linking of proteins. The biochemical mechanisms of cement polymerization remain largely unknown. We hypothesized that this process is biochemically similar to blood clotting, a critical physiological response that is also based on aggregation and cross-linking of proteins. Like key elements of vertebrate and invertebrate blood clotting, barnacle cement polymerization was shown to involve proteolytic activation of enzymes and structural precursors, transglutaminase cross-linking and assembly of fibrous proteins. Proteolytic activation of structural proteins maximizes the potential for bonding interactions with other proteins and with the surface. Transglutaminase cross-linking reinforces cement integrity. Remarkably, epitopes and sequences homologous to bovine trypsin and human transglutaminase were identified in barnacle cement with tandem mass spectrometry and/or western blotting. Akin to blood clotting, the peptides generated during proteolytic activation functioned as signal molecules, linking a molecular level event (protein aggregation) to a behavioral response (barnacle larval settlement). Our results draw attention to a highly conserved protein polymerization mechanism and shed light on a long-standing biochemical puzzle. We suggest that barnacle cement polymerization is a specialized form of wound healing. The polymerization mechanism common between barnacle cement and blood may be a theme for many marine animal glues. PMID:19837892

  16. Biochemical and genetic analysis of the role of the viral polymerase in enterovirus recombination.

    PubMed

    Woodman, Andrew; Arnold, Jamie J; Cameron, Craig E; Evans, David J

    2016-08-19

    Genetic recombination in single-strand, positive-sense RNA viruses is a poorly understand mechanism responsible for generating extensive genetic change and novel phenotypes. By moving a critical cis-acting replication element (CRE) from the polyprotein coding region to the 3' non-coding region we have further developed a cell-based assay (the 3'CRE-REP assay) to yield recombinants throughout the non-structural coding region of poliovirus from dually transfected cells. We have additionally developed a defined biochemical assay in which the only protein present is the poliovirus RNA dependent RNA polymerase (RdRp), which recapitulates the strand transfer events of the recombination process. We have used both assays to investigate the role of the polymerase fidelity and nucleotide turnover rates in recombination. Our results, of both poliovirus intertypic and intratypic recombination in the CRE-REP assay and using a range of polymerase variants in the biochemical assay, demonstrate that RdRp fidelity is a fundamental determinant of recombination frequency. High fidelity polymerases exhibit reduced recombination and low fidelity polymerases exhibit increased recombination in both assays. These studies provide the basis for the analysis of poliovirus recombination throughout the non-structural region of the virus genome and provide a defined biochemical assay to further dissect this important evolutionary process. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. An integrative top-down and bottom-up qualitative model construction framework for exploration of biochemical systems.

    PubMed

    Wu, Zujian; Pang, Wei; Coghill, George M

    Computational modelling of biochemical systems based on top-down and bottom-up approaches has been well studied over the last decade. In this research, after illustrating how to generate atomic components by a set of given reactants and two user pre-defined component patterns, we propose an integrative top-down and bottom-up modelling approach for stepwise qualitative exploration of interactions among reactants in biochemical systems. Evolution strategy is applied to the top-down modelling approach to compose models, and simulated annealing is employed in the bottom-up modelling approach to explore potential interactions based on models constructed from the top-down modelling process. Both the top-down and bottom-up approaches support stepwise modular addition or subtraction for the model evolution. Experimental results indicate that our modelling approach is feasible to learn the relationships among biochemical reactants qualitatively. In addition, hidden reactants of the target biochemical system can be obtained by generating complex reactants in corresponding composed models. Moreover, qualitatively learned models with inferred reactants and alternative topologies can be used for further web-lab experimental investigations by biologists of interest, which may result in a better understanding of the system.

  18. Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

    PubMed Central

    Xiao, Yun; Ahadian, Samad

    2017-01-01

    Progress in biomaterial science and engineering and increasing knowledge in cell biology have enabled us to develop functional biomaterials providing appropriate biochemical and biophysical cues for tissue regeneration applications. Tissue regeneration is particularly important to treat chronic wounds of people with diabetes. Understanding and controlling the cellular microenvironment of the wound tissue are important to improve the wound healing process. In this study, we review different biochemical (e.g., growth factors, peptides, DNA, and RNA) and biophysical (e.g., topographical guidance, pressure, electrical stimulation, and pulsed electromagnetic field) cues providing a functional and instructive acellular matrix to heal diabetic chronic wounds. The biochemical and biophysical signals generally regulate cell–matrix interactions and cell behavior and function inducing the tissue regeneration for chronic wounds. Some technologies and devices have already been developed and used in the clinic employing biochemical and biophysical cues for wound healing applications. These technologies can be integrated with smart biomaterials to deliver therapeutic agents to the wound tissue in a precise and controllable manner. This review provides useful guidance in understanding molecular mechanisms and signals in the healing of diabetic chronic wounds and in designing instructive biomaterials to treat them. PMID:27405960

  19. Characteristics and Concepts of Dynamic Hub Proteins in DNA Processing Machinery from Studies of RPA

    PubMed Central

    Sugitani, Norie; Chazin, Walter J.

    2015-01-01

    DNA replication, damage response and repair require the coordinated action of multi-domain proteins operating within dynamic multi-protein machines that act upon the DNA substrate. These modular proteins contain flexible linkers of various lengths, which enable changes in the spatial distribution of the globular domains (architecture) that harbor their essential biochemical functions. This mobile architecture is uniquely suited to follow the evolving substrate landscape present over the course of the specific process performed by the multi-protein machinery. A fundamental advance in understanding of protein machinery is the realization of the pervasive role of dynamics. Not only is the machine undergoing dynamic transformations, but the proteins themselves are flexible and constantly adapting to the progression through the steps of the overall process. Within this dynamic context the activity of the constituent proteins must be coordinated, a role typically played by hub proteins. A number of important characteristics of modular proteins and concepts about the operation of dynamic machinery have been discerned. These provide the underlying basis for the action of the machinery that reads DNA, and responds to and repairs DNA damage. Here, we introduce a number of key characteristics and concepts, including the modularity of the proteins, linkage of weak binding sites, direct competition between sites, and allostery, using the well recognized hub protein replication protein A (RPA). PMID:25542993

  20. Biotechnological advances towards an enhanced peroxidase production in Pichia pastoris.

    PubMed

    Krainer, Florian W; Gerstmann, Michaela A; Darnhofer, Barbara; Birner-Gruenberger, Ruth; Glieder, Anton

    2016-09-10

    Horseradish peroxidase (HRP) is a high-demand enzyme for applications in diagnostics, bioremediation, biocatalysis and medicine. Current HRP preparations are isolated from horseradish roots as mixtures of biochemically diverse isoenzymes. Thus, there is a strong need for a recombinant production process enabling a steady supply with enzyme preparations of consistent high quality. However, most current recombinant production systems are limited at titers in the low mg/L range. In this study, we used the well-known yeast Pichia pastoris as host for recombinant HRP production. To enhance recombinant enzyme titers we systematically evaluated engineering approaches on the secretion process, coproduction of helper proteins, and compared expression from the strong methanol-inducible PAOX1 promoter, the strong constitutive PGAP promoter, and a novel bidirectional promoter PHTX1. Ultimately, coproduction of HRP and active Hac1 under PHTX1 control yielded a recombinant HRP titer of 132mg/L after 56h of cultivation in a methanol-independent and easy-to-do bioreactor cultivation process. With regard to the many versatile applications for HRP, the establishment of a microbial host system suitable for efficient recombinant HRP production was highly overdue. The novel HRP production platform in P. pastoris presented in this study sets a new benchmark for this medically relevant enzyme. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

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