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Sample records for nuclear jungle compartmentalization

  1. Nuclear compartmentalization of DNA repair.

    PubMed

    Kalousi, Alkmini; Soutoglou, Evi

    2016-04-01

    The continuous threats on genome integrity by endogenous and exogenous sources have rendered cells competent to overcome these challenges by activating DNA repair pathways. A complex network of proteins and their modifications participate in orchestrated signaling cascades, which are induced in response to DNA damage and may determine the choice of repair pathway. In this review, we summarize recent findings in the field of DNA Double Strand Break repair with regard to the positioning of the break in the highly compartmentalized nucleus. We aim to highlight the importance of chromatin state along with the nuclear position of the DNA lesions on the choice of DNA repair pathway and maintenance of genome integrity. PMID:27266837

  2. Demonstration of nuclear compartmentalization of glutathione in hepatocytes.

    PubMed Central

    Bellomo, G; Vairetti, M; Stivala, L; Mirabelli, F; Richelmi, P; Orrenius, S

    1992-01-01

    The intracellular distribution of glutathione (GSH) in cultured hepatocytes has been investigated by using the compound monochlorobimane (BmCl), which interacts specifically with GSH to form a highly fluorescent adduct. Image analysis of BmCl-labeled hepatocytes predominantly localized the fluorescence in the nucleus; the nuclear/cytoplasmic concentration gradient was approximately three. This concentration gradient was collapsed by treatment of the cells with ATP-depleting agents. The uneven distribution of BmCl fluorescence was not attributable to (i) nonspecific interaction of BmCl with protein sulfhydryl groups, (ii) any selective nuclear localization of the GSH transferase(s) catalyzing formation of the GSH-BmCl conjugate, or (iii) any apparent alterations in cell morphology from culture conditions, suggesting that this distribution did, indeed, reflect a nuclear compartmentalization of GSH. That the nuclear pool of GSH was found more resistant to depletion by several agents than the cytoplasmic pool supports the assumption that GSH is essential in protecting DNA and other nuclear structures from chemical injury. Images PMID:1584774

  3. Nuclear matrix and structural and functional compartmentalization of the eucaryotic cell nucleus.

    PubMed

    Razin, S V; Borunova, V V; Iarovaia, O V; Vassetzky, Y S

    2014-07-01

    Becoming popular at the end of the 20th century, the concept of the nuclear matrix implies the existence of a nuclear skeleton that organizes functional elements in the cell nucleus. This review presents a critical analysis of the results obtained in the study of nuclear matrix in the light of current views on the organization of the cell nucleus. Numerous studies of nuclear matrix have failed to provide evidence of the existence of such a structure. Moreover, the existence of a filamentous structure that supports the nuclear compartmentalization appears to be unnecessary, since this function is performed by the folded genome itself.

  4. Substrate-induced Nuclear Export and Peripheral Compartmentalization of Hepatic Glucokinase Correlates with Glycogen Deposition

    PubMed Central

    Shiota, Masa; Knobel, Susan M.; Piston, David W.; Cherrington, Alan D.; Magnuson, Mark A.

    2001-01-01

    Hepatic glucokinase (GK) is acutely regulated by binding to its nuclear-anchored regulatory protein (GKRP). Although GK release by GKRP is tightly coupled to the rate of glycogen synthesis, the nature of this association is obscure. To gain insight into this coupling mechanism under physiological stimulating conditions in primary rat hepatocytes, we analyzed the subcellular distribution of GK and GKRP with immunofluorescence, and glycogen deposition with glycogen cytochemical fluorescence, using confocal microscopyand quantitative image analysis. Following stimulation, a fraction of the GK signal translocated from the nucleus to the cytoplasm. The reduction in the nuclear to cytoplasmic ratio of GK, an index of nuclear export, correlated with a >50% increase in glycogen cytochemical fluorescence over a 60min stimulation period. Furthermore, glycogen accumulation was initially deposited in a peripheral pattern in hepatocytes similar to that of GK. These data suggest that a compartmentalization exists of both active GK and the initial sites of glycogen deposition at the hepatocyte surface. PMID:12369705

  5. Compositional compartmentalization and compositional patterns in the nuclear genomes of plants.

    PubMed Central

    Salinas, J; Matassi, G; Montero, L M; Bernardi, G

    1988-01-01

    We report here results which indicate (i) that the nuclear genomes of angiosperms is characterized by a compositional compartmentalization and an isochore structure; and (ii) that the nuclear genomes of some Gramineae exhibit strikingly different compositional patterns compared to those of many dicots. Indeed, the compositional distribution of nuclear DNA molecules (in the 50-100 Kb size range) from three dicots (pea, sunflower and tobacco) and three monocots (maize, rice and wheat) were found to be centered around lower (41%) and higher (45% for rice, 48% for maize and wheat) GC levels, respectively (and to trail towards even higher GC values in maize and wheat). Experiments on gene localization in density gradient fractions showed a remarkable compositional homogeneity in vast (greater than 100-200 Kb) regions surrounding the genes. On the other hand, the compositional distribution of coding sequences (GenBank and literature data) from dicots (several orders) was found to be narrow, symmetrical and centered around 46% GC, that from monocots (essentially barley, maize and wheat) to be broad, asymmetrical and characterized by an upward trend towards high GC values, with the majority of sequences between 60 and 70% GC. Introns exhibited a similar compositional distribution, but lower GC levels, compared to exons from the same genes. Images PMID:3380684

  6. Nuclear Compartmentalization of α1-Adrenergic Receptor Signaling in Adult Cardiac Myocytes

    PubMed Central

    Wu, Steven C.

    2015-01-01

    Abstract: Although convention dictates that G protein-coupled receptors localize to and signal at the plasma membrane, accumulating evidence suggests that G protein-coupled receptors localize to and signal at intracellular membranes, most notably the nucleus. In fact, there is now significant evidence indicating that endogenous alpha-1 adrenergic receptors (α1-ARs) localize to and signal at the nuclei in adult cardiac myocytes. Cumulatively, the data suggest that α1-ARs localize to the inner nuclear membrane, activate intranuclear signaling, and regulate physiologic function in adult cardiac myocytes. Although α1-ARs signal through Gαq, unlike other Gq-coupled receptors, α1-ARs mediate important cardioprotective functions including adaptive/physiologic hypertrophy, protection from cell death (survival signaling), positive inotropy, and preconditioning. Also unlike other Gq-coupled receptors, most, if not all, functional α1-ARs localize to the nuclei in adult cardiac myocytes, as opposed to the sarcolemma. Together, α1-AR nuclear localization and cardioprotection might suggest a novel model for compartmentalization of Gq-coupled receptor signaling in which nuclear Gq-coupled receptor signaling is cardioprotective. PMID:25264754

  7. Compartmentalization and Functionality of Nuclear Disorder: Intrinsic Disorder and Protein-Protein Interactions in Intra-Nuclear Compartments

    PubMed Central

    Meng, Fanchi; Na, Insung; Kurgan, Lukasz; Uversky, Vladimir N.

    2015-01-01

    The cell nucleus contains a number of membrane-less organelles or intra-nuclear compartments. These compartments are dynamic structures representing liquid-droplet phases which are only slightly denser than the bulk intra-nuclear fluid. They possess different functions, have diverse morphologies, and are typically composed of RNA (or, in some cases, DNA) and proteins. We analyzed 3005 mouse proteins localized in specific intra-nuclear organelles, such as nucleolus, chromatin, Cajal bodies, nuclear speckles, promyelocytic leukemia (PML) nuclear bodies, nuclear lamina, nuclear pores, and perinuclear compartment and compared them with ~29,863 non-nuclear proteins from mouse proteome. Our analysis revealed that intrinsic disorder is enriched in the majority of intra-nuclear compartments, except for the nuclear pore and lamina. These compartments are depleted in proteins that lack disordered domains and enriched in proteins that have multiple disordered domains. Moonlighting proteins found in multiple intra-nuclear compartments are more likely to have multiple disordered domains. Protein-protein interaction networks in the intra-nuclear compartments are denser and include more hubs compared to the non-nuclear proteins. Hubs in the intra-nuclear compartments (except for the nuclear pore) are enriched in disorder compared with non-nuclear hubs and non-nuclear proteins. Therefore, our work provides support to the idea of the functional importance of intrinsic disorder in the cell nucleus and shows that many proteins associated with sub-nuclear organelles in nuclei of mouse cells are enriched in disorder. This high level of disorder in the mouse nuclear proteins defines their ability to serve as very promiscuous binders, possessing both large quantities of potential disorder-based interaction sites and the ability of a single such site to be involved in a large number of interactions. PMID:26712748

  8. Compartmentalization and Functionality of Nuclear Disorder: Intrinsic Disorder and Protein-Protein Interactions in Intra-Nuclear Compartments.

    PubMed

    Meng, Fanchi; Na, Insung; Kurgan, Lukasz; Uversky, Vladimir N

    2015-12-25

    The cell nucleus contains a number of membrane-less organelles or intra-nuclear compartments. These compartments are dynamic structures representing liquid-droplet phases which are only slightly denser than the bulk intra-nuclear fluid. They possess different functions, have diverse morphologies, and are typically composed of RNA (or, in some cases, DNA) and proteins. We analyzed 3005 mouse proteins localized in specific intra-nuclear organelles, such as nucleolus, chromatin, Cajal bodies, nuclear speckles, promyelocytic leukemia (PML) nuclear bodies, nuclear lamina, nuclear pores, and perinuclear compartment and compared them with ~29,863 non-nuclear proteins from mouse proteome. Our analysis revealed that intrinsic disorder is enriched in the majority of intra-nuclear compartments, except for the nuclear pore and lamina. These compartments are depleted in proteins that lack disordered domains and enriched in proteins that have multiple disordered domains. Moonlighting proteins found in multiple intra-nuclear compartments are more likely to have multiple disordered domains. Protein-protein interaction networks in the intra-nuclear compartments are denser and include more hubs compared to the non-nuclear proteins. Hubs in the intra-nuclear compartments (except for the nuclear pore) are enriched in disorder compared with non-nuclear hubs and non-nuclear proteins. Therefore, our work provides support to the idea of the functional importance of intrinsic disorder in the cell nucleus and shows that many proteins associated with sub-nuclear organelles in nuclei of mouse cells are enriched in disorder. This high level of disorder in the mouse nuclear proteins defines their ability to serve as very promiscuous binders, possessing both large quantities of potential disorder-based interaction sites and the ability of a single such site to be involved in a large number of interactions.

  9. Functional redundancy in the nuclear compartmentalization of the late-replicating genome

    PubMed Central

    Ragoczy, Tobias; Telling, Agnes; Scalzo, David; Kooperberg, Charles; Groudine, Mark

    2014-01-01

    The eukaryotic nucleus is structurally and functionally organized, as reflected in the distribution of its protein and DNA components. The genome itself is segregated into euchromatin and heterochromatin that replicate in a distinct spatio-temporal manner. We used a combination of fluorescence in situ hybridization (FISH) and DamID to investigate the localization of the early and late replicating components of the genome in a lymphoblastoid cell background. Our analyses revealed that the bulk of late replicating chromatin localizes to the nuclear peripheral heterochromatin (PH) in a chromosome size and gene density dependent manner. Late replicating DNA on small chromosomes exhibits a much lower tendency to localize to PH and tends to associate with alternate repressive subcompartments such as pericentromeric (PCH) and perinucleolar heterochromatin (PNH). Furthermore, multicolor FISH analysis revealed that late replicating loci, particularly on the smaller chromosomes, may associate with any of these 3 repressive subcompartments, including more than one at the same time. These results suggest a functional equivalence or redundancy among the 3 subcompartments. Consistent with this notion, disruption of nucleoli resulted in an increased association of late replicating loci with peripheral heterochromatin. Our analysis reveals that rather than considering the morphologically distinct PH, PCH and PNH as individual subcompartments, they should be considered in aggregate as a functional compartment for late replicating chromatin. PMID:25493640

  10. Functional redundancy in the nuclear compartmentalization of the late-replicating genome.

    PubMed

    Ragoczy, Tobias; Telling, Agnes; Scalzo, David; Kooperberg, Charles; Groudine, Mark

    2014-01-01

    The eukaryotic nucleus is structurally and functionally organized, as reflected in the distribution of its protein and DNA components. The genome itself is segregated into euchromatin and heterochromatin that replicate in a distinct spatio-temporal manner. We used a combination of fluorescence in situ hybridization (FISH) and DamID to investigate the localization of the early and late replicating components of the genome in a lymphoblastoid cell background. Our analyses revealed that the bulk of late replicating chromatin localizes to the nuclear peripheral heterochromatin (PH) in a chromosome size and gene density dependent manner. Late replicating DNA on small chromosomes exhibits a much lower tendency to localize to PH and tends to associate with alternate repressive subcompartments such as pericentromeric (PCH) and perinucleolar heterochromatin (PNH). Furthermore, multicolor FISH analysis revealed that late replicating loci, particularly on the smaller chromosomes, may associate with any of these 3 repressive subcompartments, including more than one at the same time. These results suggest a functional equivalence or redundancy among the 3 subcompartments. Consistent with this notion, disruption of nucleoli resulted in an increased association of late replicating loci with peripheral heterochromatin. Our analysis reveals that rather than considering the morphologically distinct PH, PCH and PNH as individual subcompartments, they should be considered in aggregate as a functional compartment for late replicating chromatin. PMID:25493640

  11. Estimate of FDG excretion by means of compartmental analysis and ant colony optimization of nuclear medicine data.

    PubMed

    Garbarino, Sara; Caviglia, Giacomo; Brignone, Massimo; Massollo, Michela; Sambuceti, Gianmario; Piana, Michele

    2013-01-01

    [(18)F]fluoro-2-deoxy-D-glucose (FDG) is one of the most utilized tracers for positron emission tomography (PET) applications in oncology. FDG-PET relies on higher glycolytic activity in tumors compared to normal structures as the basis of image contrast. As a glucose analog, FDG is transported into malignant cells which typically exhibit an increased radioactivity. However, different from glucose, FDG is not reabsorbed by the renal system and is excreted to the bladder. The present paper describes a novel computational method for the quantitative assessment of this excretion process. The method is based on a compartmental analysis of FDG-PET data in which the excretion process is explicitly accounted for by the bladder compartment and on the application of an ant colony optimization (ACO) algorithm for the determination of the tracer coefficients describing the FDG transport effectiveness. The validation of this approach is performed by means of both synthetic data and real measurements acquired by a PET device for small animals (micro-PET). Possible oncological applications of the results are discussed in the final section. PMID:24191175

  12. How Should We Teach "The Jungle"?

    ERIC Educational Resources Information Center

    Phelps, Christopher

    2006-01-01

    Upton Sinclair's "The Jungle" describes a callous America in which the dollar trumps justice. It famously exposed the American meatpacking industry's loathsome practices and prompted federal consumer-protection laws. It is, however, primarily a sympathetic sketch of the foreign born, those fabled "masses yearning to breathe free" that Americans…

  13. A Five-Species Jungle Game.

    PubMed

    Kang, Yibin; Pan, Qiuhui; Wang, Xueting; He, Mingfeng

    2016-01-01

    In this paper, we investigate the five-species Jungle game in the framework of evolutionary game theory. We address the coexistence and biodiversity of the system using mean-field theory and Monte Carlo simulations. Then, we find that the inhibition from the bottom-level species to the top-level species can be critical factors that affect biodiversity, no matter how it is distributed, whether homogeneously well mixed or structured. We also find that predators' different preferences for food affect species' coexistence. PMID:27332995

  14. A Five-Species Jungle Game

    PubMed Central

    Kang, Yibin; Pan, Qiuhui; Wang, Xueting; He, Mingfeng

    2016-01-01

    In this paper, we investigate the five-species Jungle game in the framework of evolutionary game theory. We address the coexistence and biodiversity of the system using mean-field theory and Monte Carlo simulations. Then, we find that the inhibition from the bottom-level species to the top-level species can be critical factors that affect biodiversity, no matter how it is distributed, whether homogeneously well mixed or structured. We also find that predators’ different preferences for food affect species’ coexistence. PMID:27332995

  15. Divide Et Impera--cellular auxin compartmentalization.

    PubMed

    Barbez, Elke; Kleine-Vehn, Jürgen

    2013-02-01

    The phytohormone auxin is an essential regulator for plant growth and development. Decades of intensive research revealed the mutual importance of auxin metabolism and intercellular cell-to-cell transport for the regulation of spatiotemporal auxin distribution. Just recently, intracellular putative auxin carriers, such as the PIN-FORMED (PIN)5/PIN8 and the PIN-LIKES (PILS)2/PILS5 were discovered at the endoplasmic reticulum (ER) and seem to limit nuclear auxin signaling via an auxin sequestration mechanism. Moreover, these auxin carriers at the ER might provide a link between auxin compartmentalization and auxin conjugation-based metabolism. Here we review the recent findings on auxin compartmentalization at the ER and discuss its potential contribution to cellular auxin homeostasis and its importance for plant development. PMID:23200033

  16. Toxoplasmosis in military personnel involved in jungle operations.

    PubMed

    Gómez-Marín, Jorge Enrique; de-la-Torre, Alejandra; Barrios, Patricia; Cardona, Nestor; Álvarez, Catalina; Herrera, Claudia

    2012-04-01

    Tropical diseases, mainly leishmaniasis and malaria, increased among Colombian military personnel due to intensive operations in the jungle in the last ten years; as a result the Colombian army developed important preventive strategies for malaria and leishmaniasis. However, no knowledge exists about toxoplasmosis, an emergent disease in military personnel. We compared the prevalence of IgG anti-Toxoplasma antibodies by ELISA and of parasitaemia by a real time PCR assay, in 500 professional soldiers that operated in the jungle with a group of 501 soldiers working in an urban zone (Bogotá). We found that the prevalence was significantly different between both groups of soldiers (80% in soldiers operating in jungle vs. 45% in urban soldiers, adjusted OR 11.4; CI 95%: 3.8-34; p<0.0001). All soldiers operating in the jungle drink unboiled and chlorine untreated lake or river water. In urban soldiers, these risk factors along with eating wild animal meat or eating tigrillo (little spotted cat) were significantly associated with a higher prevalence. Characteristic toxoplasmic choriorretinal lesions were found in 4 soldiers that operated in the jungle (0.8%) and in one urban soldier (0.19%). All soldiers before being deployed in jungle operations should be tested for Toxoplasma antibodies and to receive adequate health information about the routine use of personnel filters to purify their water for consumption.

  17. Cellular compartmentalization of secondary metabolism

    PubMed Central

    Kistler, H. Corby; Broz, Karen

    2015-01-01

    Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g., amino acids, acetyl CoA, NADPH), enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported. PMID:25709603

  18. Physiology Education and the Linguistic Jungle of Science

    ERIC Educational Resources Information Center

    Nordquist, Lina

    2008-01-01

    Life sciences can be complicated enough without getting into the names of all its Dalton-scale participants. For many students, composing a project plan or writing a paper is rather like learning a foreign language. In this article, the author argues that there is a linguistic jungle of science, and it may well discourage students from pursuing a…

  19. Current Ideas about Prebiological Compartmentalization

    PubMed Central

    Monnard, Pierre-Alain; Walde, Peter

    2015-01-01

    Contemporary biological cells are highly sophisticated dynamic compartment systems which separate an internal volume from the external medium through a boundary, which controls, in complex ways, the exchange of matter and energy between the cell’s interior and the environment. Since such compartmentalization is a fundamental principle of all forms of life, scenarios have been elaborated about the emergence of prebiological compartments on early Earth, in particular about their likely structural characteristics and dynamic features. Chemical systems that consist of potentially prebiological compartments and chemical reaction networks have been designed to model pre-cellular systems. These systems are often referred to as “protocells”. Past and current protocell model systems are presented and compared. Since the prebiotic formation of cell-like compartments is directly linked to the prebiotic availability of compartment building blocks, a few aspects on the likely chemical inventory on the early Earth are also summarized. PMID:25867709

  20. Compartmentalization of prokaryotic DNA replication.

    PubMed

    Bravo, Alicia; Serrano-Heras, Gemma; Salas, Margarita

    2005-01-01

    It becomes now apparent that prokaryotic DNA replication takes place at specific intracellular locations. Early studies indicated that chromosomal DNA replication, as well as plasmid and viral DNA replication, occurs in close association with the bacterial membrane. Moreover, over the last several years, it has been shown that some replication proteins and specific DNA sequences are localized to particular subcellular regions in bacteria, supporting the existence of replication compartments. Although the mechanisms underlying compartmentalization of prokaryotic DNA replication are largely unknown, the docking of replication factors to large organizing structures may be important for the assembly of active replication complexes. In this article, we review the current state of this subject in two bacterial species, Escherichia coli and Bacillus subtilis, focusing our attention in both chromosomal and extrachromosomal DNA replication. A comparison with eukaryotic systems is also presented.

  1. Current Ideas about Prebiological Compartmentalization.

    PubMed

    Monnard, Pierre-Alain; Walde, Peter

    2015-01-01

    Contemporary biological cells are highly sophisticated dynamic compartment systems which separate an internal volume from the external medium through a boundary, which controls, in complex ways, the exchange of matter and energy between the cell's interior and the environment. Since such compartmentalization is a fundamental principle of all forms of life, scenarios have been elaborated about the emergence of prebiological compartments on early Earth, in particular about their likely structural characteristics and dynamic features. Chemical systems that consist of potentially prebiological compartments and chemical reaction networks have been designed to model pre-cellular systems. These systems are often referred to as "protocells". Past and current protocell model systems are presented and compared. Since the prebiotic formation of cell-like compartments is directly linked to the prebiotic availability of compartment building blocks, a few aspects on the likely chemical inventory on the early Earth are also summarized. PMID:25867709

  2. Protocell design through modular compartmentalization.

    PubMed

    Miller, David; Booth, Paula J; Seddon, John M; Templer, Richard H; Law, Robert V; Woscholski, Rudiger; Ces, Oscar; Barter, Laura M C

    2013-10-01

    De novo synthetic biological design has the potential to significantly impact upon applications such as energy generation and nanofabrication. Current designs for constructing organisms from component parts are typically limited in scope, as they utilize a cut-and-paste ideology to create simple stepwise engineered protein-signalling pathways. We propose the addition of a new design element that segregates components into lipid-bound 'proto-organelles', which are interfaced with response elements and housed within a synthetic protocell. This design is inspired by living cells, which utilize multiple types of signalling molecules to facilitate communication between isolated compartments. This paper presents our design and validation of the components required for a simple multi-compartment protocell machine, for coupling a light transducer to a gene expression system. This represents a general design concept for the compartmentalization of different types of artificial cellular machinery and the utilization of non-protein signal molecules for signal transduction. PMID:23925982

  3. Protocell design through modular compartmentalization

    PubMed Central

    Miller, David; Booth, Paula J.; Seddon, John M.; Templer, Richard H.; Law, Robert V.; Woscholski, Rudiger; Ces, Oscar; Barter, Laura M. C.

    2013-01-01

    De novo synthetic biological design has the potential to significantly impact upon applications such as energy generation and nanofabrication. Current designs for constructing organisms from component parts are typically limited in scope, as they utilize a cut-and-paste ideology to create simple stepwise engineered protein-signalling pathways. We propose the addition of a new design element that segregates components into lipid-bound ‘proto-organelles’, which are interfaced with response elements and housed within a synthetic protocell. This design is inspired by living cells, which utilize multiple types of signalling molecules to facilitate communication between isolated compartments. This paper presents our design and validation of the components required for a simple multi-compartment protocell machine, for coupling a light transducer to a gene expression system. This represents a general design concept for the compartmentalization of different types of artificial cellular machinery and the utilization of non-protein signal molecules for signal transduction. PMID:23925982

  4. Compartmentalization of the endoplasmic reticulum in the early C. elegans embryos.

    PubMed

    Lee, Zuo Yen; Prouteau, Manoël; Gotta, Monica; Barral, Yves

    2016-09-12

    The one-cell Caenorhabditis elegans embryo is polarized to partition fate determinants between the cell lineages generated during its first division. Using fluorescence loss in photobleaching, we find that the endoplasmic reticulum (ER) of the C. elegans embryo is physically continuous throughout the cell, but its membrane is compartmentalized shortly before nuclear envelope breakdown into an anterior and a posterior domain, indicating that a diffusion barrier forms in the ER membrane between these two domains. Using mutants with disorganized ER, we show that ER compartmentalization is independent of the morphological transition that the ER undergoes in mitosis. In contrast, compartmentalization takes place at the position of the future cleavage plane in a par-3-dependent manner. Together, our data indicate that the ER membrane is compartmentalized in cells as diverse as budding yeast, mouse neural stem cells, and the early C. elegans embryo. PMID:27597753

  5. Redox compartmentalization in eukaryotic cells

    PubMed Central

    Go, Young-Mi; Jones, Dean P.

    2008-01-01

    Diverse functions of eukaryotic cells are optimized by organization of compatible chemistries into distinct compartments defined by the structures of lipid-containing membranes, multiprotein complexes and oligomeric structures of saccharides and nucleic acids. This structural and chemical organization is coordinated, in part, through cysteine residues of proteins which undergo reversible oxidation-reduction and serve as chemical/structural transducing elements. The central thiol/disulfide redox couples, thioredoxin-1, thioredoxin-2, GSH/GSSG and cysteine/cystine (Cys/CySS), are not in equilibrium with each other and are maintained at distinct, non-equilibrium potentials in mitochondria, nuclei, the secretory pathway and the extracellular space. Mitochondria contain the most reducing compartment, have the highest rates of electron transfer and are highly sensitive to oxidation. Nuclei also have more reduced redox potentials but are relatively resistant to oxidation. The secretory pathway contains oxidative systems which introduce disulfides into proteins for export. The cytoplasm contains few metabolic oxidases and this maintains an environment for redox signaling dependent upon NADPH oxidases and NO synthases. Extracellular compartments are maintained at stable oxidizing potentials. Controlled changes in cytoplasmic GSH/GSSG redox potential are associated with functional state, varying with proliferation, differentiation and apoptosis. Variation in extracellular Cys/CySS redox potential is also associated with proliferation, cell adhesion and apoptosis. Thus, cellular redox biology is inseparable from redox compartmentalization. Further elucidation of the redox control networks within compartments will improve the mechanistic understanding of cell functions and their disruption in disease. PMID:18267127

  6. Compartmentalized storage tank for electrochemical cell system

    NASA Technical Reports Server (NTRS)

    Piecuch, Benjamin Michael (Inventor); Dalton, Luke Thomas (Inventor)

    2010-01-01

    A compartmentalized storage tank is disclosed. The compartmentalized storage tank includes a housing, a first fluid storage section disposed within the housing, a second fluid storage section disposed within the housing, the first and second fluid storage sections being separated by a movable divider, and a constant force spring. The constant force spring is disposed between the housing and the movable divider to exert a constant force on the movable divider to cause a pressure P1 in the first fluid storage section to be greater than a pressure P2 in the second fluid storage section, thereby defining a pressure differential.

  7. Tick fauna of Malaysian red jungle fowl (Gallus gallus) in Bangi, Malaysia

    PubMed Central

    Konto, M.; Fufa, G. I.; Zakaria, A.; Tukur, S. M.; Watanabe, M.; Ola-Fadunsin, S. D.; Khan, M. S.; Shettima, Y. M.; Babjee, S. M. A.

    2015-01-01

    Aim: The red jungle fowl is generally considered as one of the endangered Asian wild Galleopheasants due to man-made encroachment of their habitats, coupled with the effect of disease and disease causing organisms like ticks and tick-borne infections. This study aimed to determine the tick fauna of the red jungle fowl and their predilection sites based on developmental stages. Materials and Methods: A total of 33 jungle fowls were sampled for this study from Bangi area of Selangor State, Peninsular Malaysian. The birds were captured using a locally made trap made-up of loops and bites. Ticks present on their bodies were detached using fine forceps and identified morphologically under a dissecting microscope. Results: 91% of the jungle fowls were infested with ticks, all of which belongs to the species Haemaphysalis wellingtoni. The ear region appeared to be the most common predilection site (63%) for all the developmental stages in which the larval stages are solely restricted to that region. Nymphal and adult stages were distributed on the comb, wattle, and facial region in addition to the ear region. Conclusion: This study was the first in its kind and showed a high prevalence of tick infestation among jungle fowls. H. wellingtoni was known to be a vector in transmission of many tick-borne pathogens. Therefore, there is the need for further investigation to identify the various pathogens associated with this tick. PMID:27047012

  8. Jungle honey enhances immune function and antitumor activity.

    PubMed

    Fukuda, Miki; Kobayashi, Kengo; Hirono, Yuriko; Miyagawa, Mayuko; Ishida, Takahiro; Ejiogu, Emenike C; Sawai, Masaharu; Pinkerton, Kent E; Takeuchi, Minoru

    2011-01-01

    Jungle honey (JH) is collected from timber and blossom by wild honey bees that live in the tropical forest of Nigeria. JH is used as a traditional medicine for colds, skin inflammation and burn wounds as well as general health care. However, the effects of JH on immune functions are not clearly known. Therefore, we investigated the effects of JH on immune functions and antitumor activity in mice. Female C57BL/6 mice were injected with JH (1 mg/mouse/day, seven times intra-peritoneal). After seven injections, peritoneal cells (PC) were obtained. Antitumor activity was assessed by growth of Lewis Lung Carcinoma/2 (LL/2) cells. PC numbers were increased in JH-injected mice compared to control mice. In Dot Plot analysis by FACS, a new cell population appeared in JH-injected mice. The percent of Gr-1 surface antigen and the intensity of Gr-1 antigen expression of PC were increased in JH-injected mice. The new cell population was neutrophils. JH possessed chemotactic activity for neutrophils. Tumor incidence and weight were decreased in JH-injected mice. The ratio of reactive oxygen species (ROS) producing cells was increased in JH-injected mice. The effective component in JH was fractionized by gel filtration using HPLC and had an approximate molecular weight (MW) of 261. These results suggest that neutrophils induced by JH possess potent antitumor activity mediated by ROS and the effective immune component of JH is substrate of MW 261. PMID:19141489

  9. Outbreak of human rabies in the Peruvian jungle.

    PubMed

    Lopez, A; Miranda, P; Tejada, E; Fishbein, D B

    1992-02-15

    Transmission of rabies to man by vampire bats has been known for 60 years but there have been few reports of the features of rabies transmitted in this way. These aspects of the disease were investigated during an outbreak in Peru in early 1990. Between Jan 1 and April 30, 1990, 29 (5%) of 636 residents of the two rural communities in the Amazon Jungle in Peru acquired an illness characterised by hydrophobia, fever, and headache and died shortly thereafter. A census in one of the two towns revealed that the proportion affected was significantly higher for 5-14 year olds (17%) than for other age-groups (p less than 10(-5). Interviews conducted with 23 of the patients or their families revealed that 22 (96%) had a history of bat bite, compared with 66 (22%) of 301 community members who remained healthy (p less than 10(-6). A rabies virus strain identical to those isolated from vampire bats (Desmodus rotundus) was isolated from the brain of the only person on whom necropsy could be done. Because of the extreme isolation of this and other communities affected by bat-transmitted rabies, preventive measures should be directed at decreasing the risk of nocturnal exposure to bats by bat proofing dwellings or use of mosquito nets and at prompt wound care. Rabies pre-exposure or postexposure vaccination is clearly indicated, but may not be feasible in these isolated populations. PMID:1346669

  10. Jesus and Maria in the Jungle: An Essay on Possibility and Constraint in the Third-Shift Third Space

    ERIC Educational Resources Information Center

    Bruna, Katherine Richardson

    2009-01-01

    One hundred years ago, Upton Sinclair, in "The Jungle," exposed the deplorable working conditions of eastern European immigrants in the meatpacking houses of Chicago. The backdrop of this article is the new Jungle of the 21st century--the hog plants of the rural Midwest. Here I speak to the lives of the Mexican workers they employ, and, more…

  11. Compartmentalized Platforms for Neuro-pharmacological Research

    PubMed Central

    Jadhav, Amol D.; Wei, Li; Shi, Peng

    2016-01-01

    Dissociated primary neuronal cell culture remains an indispensable approach for neurobiology research in order to investigate basic mechanisms underlying diverse neuronal functions, drug screening and pharmacological investigation. Compartmentalization, a widely adopted technique since its emergence in 1970s enables spatial segregation of neuronal segments and detailed investigation that is otherwise limited with traditional culture methods. Although these compartmental chambers (e.g. Campenot chamber) have been proven valuable for the investigation of Peripheral Nervous System (PNS) neurons and to some extent within Central Nervous System (CNS) neurons, their utility has remained limited given the arduous manufacturing process, incompatibility with high-resolution optical imaging and limited throughput. The development in the area of microfabrication and microfluidics has enabled creation of next generation compartmentalized devices that are cheap, easy to manufacture, require reduced sample volumes, enable precise control over the cellular microenvironment both spatially as well as temporally, and permit highthroughput testing. In this review we briefly evaluate the various compartmentalization tools used for neurobiological research, and highlight application of the emerging microfluidic platforms towards in vitro single cell neurobiology. PMID:26813122

  12. Mitochondrial RNA granules: Compartmentalizing mitochondrial gene expression

    PubMed Central

    Jourdain, Alexis A.; Boehm, Erik; Maundrell, Kinsey

    2016-01-01

    In mitochondria, DNA replication, gene expression, and RNA degradation machineries coexist within a common nondelimited space, raising the question of how functional compartmentalization of gene expression is achieved. Here, we discuss the recently characterized “mitochondrial RNA granules,” mitochondrial subdomains with an emerging role in the regulation of gene expression. PMID:26953349

  13. COMPARTMENTAL MODEL OF NITRATE RETENTION IN STREAMS

    EPA Science Inventory

    A compartmental modeling approach is presented to route nitrate retention along a cascade of stream reach sections. A process transfer function is used for transient storage equations with first order reaction terms to represent nitrate uptake in the free stream, and denitrifica...

  14. Tracking Hazard Analysis Data in a Jungle of Changing Design

    SciTech Connect

    Sullivan, Robin S.; Young, Jonathan

    2006-05-14

    The biggest fear of the hazard analyst is the loss of data in the middle of the design jungle. When project schedules are demanding and design is changing rapidly it is essential that the hazard analysis data be tracked and kept current in order to provide the required project design, development, and regulatory support. Being able to identify the current information, as well as the past archived information, as the design progresses and to be able to show how the project is designing in safety through modifications based on hazard analysis results is imperative. At the DOE Hanford site in Washington State, Flour Hanford Inc is in the process of the removal and disposition of sludge from the 100 Area K Basins. The K Basins were used to store spent fuel from the operating reactors at the Hanford Site. The sludge is a by-product from the corrosion of the fuel and fuel storage canisters. The sludge removal project has been very dynamic involving the design, procurement and, more recently, the operation of processes at two basins, K East and K West. The project has an ambitious schedule with a large number of changes to design concepts. In order to support the complex K Basins project a technique to track the status of the hazard analysis data was developed. This paper will identify the most important elements of the tracking system and how it was used to assist the project in ensuring that current design data was reflected in a specific version of the hazard analysis and to show how the project was keeping up with the design and ensuring compliance with the requirements to design in safety. While the specifics of the data tracking strategy for the K Basins sludge removal project will be described in the paper, the general concepts of the strategy are applicable to similar projects requiring iteration of hazard analysis and design.

  15. Phase Separation: Linking Cellular Compartmentalization to Disease.

    PubMed

    Aguzzi, Adriano; Altmeyer, Matthias

    2016-07-01

    Eukaryotic cells are complex structures capable of coordinating numerous biochemical reactions in space and time. Key to such coordination is the subdivision of intracellular space into functional compartments. Compartmentalization can be achieved by intracellular membranes, which surround organelles and act as physical barriers. In addition, cells have developed sophisticated mechanisms to partition their inner substance in a tightly regulated manner. Recent studies provide compelling evidence that membraneless compartmentalization can be achieved by liquid demixing, a process culminating in liquid-liquid phase separation and the formation of phase boundaries. We discuss how this emerging concept may help in understanding dynamic reorganization of subcellular space and highlight its potential as a framework to explain pathological protein assembly in cancer and neurodegeneration. PMID:27051975

  16. Metabolic pathway compartmentalization: an underappreciated opportunity?

    PubMed

    Zecchin, Annalisa; Stapor, Peter C; Goveia, Jermaine; Carmeliet, Peter

    2015-08-01

    For eukaryotic cells to function properly, they divide their intracellular space in subcellular compartments, each harboring specific metabolic activities. In recent years, it has become increasingly clear that compartmentalization of metabolic pathways is a prerequisite for certain cellular functions. This has for instance been documented for cellular migration, which relies on subcellular localization of glycolysis or mitochondrial respiration in a cell type-dependent manner. Although exciting, this field is still in its infancy, partly due to the limited availability of methods to study the directionality of metabolic pathways and to visualize metabolic processes in distinct cellular compartments. Nonetheless, advances in this field may offer opportunities for innovative strategies to target deregulated compartmentalized metabolism in disease.

  17. Compartmentation of Metabolites in Regulating Epigenomes of Cancer

    PubMed Central

    Zhao, Zhiqiang; Wang, Li; Di, Li-jun

    2016-01-01

    Covalent modifications of DNA and histones are important epigenetic events and the genomewide reshaping of epigenetic markers is common in cancer. Epigenetic markers are produced by enzymatic reactions, and some of these reactions require the presence of metabolites, specifically Epigenetic Enzyme Required Metabolites (EERMs), as cofactors. Recent studies found that the abundance of these EERMs correlates with epigenetic enzyme activities. Also, the subcellular compartmentation, especially the nuclear localization of these EERMs, may play a role in regulating the activities of epigenetic enzymes. Moreover, gene-specific recruitment of enzymes that produce the EERMs in the proximity of the epigenetic modification events accompanying the regulation of gene expression, were proposed. Therefore, it is important to summarize findings of EERMs in regulating epigenetic modifications at both the DNA and histone levels, and to understand how EERMs contribute to cancer development by addressing their global versus local distribution. PMID:27258652

  18. The Garden and the Jungle: Burnett, Kipling and the Nature of Imperial Childhood

    ERIC Educational Resources Information Center

    Goodwin, Mary

    2011-01-01

    Imperial British India is the point of origin for protagonists in both Frances Hodgson Burnett's "The Secret Garden" (1911) and Rudyard Kipling's "The Jungle Books" (1894-1895), two influential children's stories in which late Victorian notions of childhood education and nature converge with those of national and imperial identity. In Burnett's…

  19. "Tales from the Brazilian Jungle": Antonio Rocha, Storyteller. Cue Sheet for Teachers.

    ERIC Educational Resources Information Center

    Rees, Elizabeth

    This performance guide is designed for teachers to use with students before and after a performance of "Tales from the Brazilian Jungle" with storyteller Antonio Rocha. The guide, called a "Cuesheet," contains four sheets for use in class. The first, "About the Performance," prepares students for understanding references to the Amazon rainforest,…

  20. Analysis of genetic diversity and phylogenetic relationships among red jungle fowls and Chinese domestic fowls.

    PubMed

    Bao, WenBin; Chen, GuoHong; Li, BiChun; Wu, XinSheng; Shu, JingTing; Wu, ShengLong; Xu, Qi; Weigend, Steffen

    2008-06-01

    Genetic diversity and phylogenetic relationships among 568 individuals of two red jungle fowl subspecies (Gallus gallus spadiceus in China and Gallus gallus gallus in Thailand) and 14 Chinese domestic chicken breeds were evaluated with 29 microstaellite loci, the genetic variability within population and genetic differentiation among population were estimated, and then genetic diversity and phylogenetic relationships were analyzed among red jungle fowls and Chinese domestic fowls. A total of 286 alleles were detected in 16 population with 29 microsatellite markers and the average number of the alleles observed in 29 microsatellite loci was 9.86+/-6.36. The overall expected heterozygosity of all population was 0.6708+/-0.0251, and the number of population deviated from Hardy-Weinberg equilibrium per locus ranged from 0 to 7. In the whole population, the average of genetic differentiation among population, measured as FST value, was 16.7% (P<0.001), and all loci contributed significantly (P<0.001) to this differentiation. It can also be seen that the deficit of heterozygotes was very high (0.015) (P<0.01). Reynolds' distance values varied between 0.036 (Xiaoshan chicken-Luyuan chicken pair) and 0.330 (G. gallus gallus-Gushi chicken pair). The Nm value ranged from 0.533 (between G. gallus gallus and Gushi chicken) to 5.833 (between Xiaoshan chicken and Luyuan chicken). An unrooted consensus tree was constructed using the neighbour-joining method and the Reynolds' genetic distance. The heavy-body sized chicken breeds, Luyuan chicken, Xiaoshan chicken, Beijing Fatty chicken, Henan Game chicken, Huainan Partridge and Langshan chicken formed one branch, and it had a close genetic relationship between Xiaoshan chicken-Luyuan chicken pair and Chahua chicken-Tibetan chicken pair. Chahua chicken and Tibetan chicken had closer genetic relationship with these two subspecies of red jungle fowl than other domestic chicken breeds. G. gallus spadiceus showed closer phylogenetic

  1. Compartmentalization of the deep cerebellar nuclei based on afferent projections and aldolase C expression.

    PubMed

    Sugihara, Izumi

    2011-09-01

    The distribution of aldolase C (zebrin II)-positive and -negative Purkinje cells (PCs) can be used to define about 20 longitudinally extended compartments in the cerebellar cortex of the rat, which may correspond to certain aspects of cerebellar functional localization. An equivalent compartmental organization may exist in the deep cerebellar nuclei (DCN). This DCN compartmentalization is primarily represented by the afferent projection pattern in the DCN. PC projections and collateral nuclear projections of olivocerebellar climbing fiber axons have a relatively localized terminal arbor in the DCN. Projections of these axons make a closed olivo-cortico-nuclear circuit to connect a longitudinal stripe-shaped cortical compartment to a small subarea in the DCN, which can be defined as a DCN compartment. The actual DCN compartmentalization, which has been revealed by systematically mapping these projections, is quite different from the cortical compartmentalization. The stripe-shaped alternation of aldolase C-positive and -negative narrow longitudinal compartments in the cerebellar cortex is transformed to the separate clustering of positive and negative compartments in the caudoventral and rostrodorsal DCN, respectively. The distinctive projection of aldolase C-positive and -negative PCs to the caudoventral and rostrodorsal DCN underlies this transformation. Accordingly, the medial cerebellar nucleus is divided into the rostrodorsal aldolase C-negative and caudoventral aldolase C-positive parts. The anterior and posterior interposed nuclei generally correspond to the aldolase C-negative and -positive parts, respectively. DCN compartmentalization is important for understanding functional localization in the DCN since it is speculated that aldolase C-positive and -negative compartments are generally associated with somatosensory and other functions, respectively. PMID:20981512

  2. Compartmentalization of the Edinburgh Human Metabolic Network

    PubMed Central

    2010-01-01

    Background Direct in vivo investigation of human metabolism is complicated by the distinct metabolic functions of various sub-cellular organelles. Diverse micro-environments in different organelles may lead to distinct functions of the same protein and the use of different enzymes for the same metabolic reaction. To better understand the complexity in the human metabolism, a compartmentalized human metabolic network with integrated sub-cellular location information is required. Results We extended the previously reconstructed Edinburgh Human Metabolic Network (EHMN) [Ma, et al. Molecular Systems Biology, 3:135, 2007] by integrating the sub-cellular location information for the reactions, adding transport reactions and refining the protein-reaction relationships based on the location information. Firstly, protein location information was obtained from Gene Ontology and complemented by a Swiss-Prot location keywords search. Then all the reactions in EHMN were assigned to a location based on the protein-reaction relationships to get a preliminary compartmentalized network. We investigated the localized sub-networks in each pathway to identify gaps and isolated reactions by connectivity analysis and refined the location information based on information from literature. As a result, location information for hundreds of reactions was revised and hundreds of incorrect protein-reaction relationships were corrected. Over 1400 transport reactions were added to link the location specific metabolic network. To validate the network, we have done pathway analysis to examine the capability of the network to synthesize or degrade certain key metabolites. Compared with a previously published human metabolic network (Human Recon 1), our network contains over 1000 more reactions assigned to clear cellular compartments. Conclusions By combining protein location information, network connectivity analysis and manual literature search, we have reconstructed a more complete

  3. Compartmentalized ATP synthesis in skeletal muscle triads.

    PubMed

    Han, J W; Thieleczek, R; Varsányi, M; Heilmeyer, L M

    1992-01-21

    Isolated skeletal muscle triads contain a compartmentalized glycolytic reaction sequence catalyzed by aldolase, triosephosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, and phosphoglycerate kinase. These enzymes express activity in the structure-associated state leading to synthesis of ATP in the triadic junction upon supply of glyceraldehyde 3-phosphate or fructose 1,6-bisphosphate. ATP formation occurs transiently and appears to be kinetically compartmentalized, i.e., the synthesized ATP is not in equilibrium with the bulk ATP. The apparent rate constants of the aldolase and the glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase reaction are significantly increased when fructose 1,6-bisphosphate instead of glyceraldehyde 3-phosphate is employed as substrate. The observations suggest that fructose 1,6-bisphosphate is especially effectively channelled into the junctional gap. The amplitude of the ATP transient is decreasing with increasing free [Ca2+] in the range of 1 nM to 30 microM. In the presence of fluoride, the ATP transient is significantly enhanced and its declining phase is substantially retarded. This observation suggests utilization of endogenously synthesized ATP in part by structure associated protein kinases and phosphatases which is confirmed by the detection of phosphorylated triadic proteins after gel electrophoresis and autoradiography. Endogenous protein kinases phosphorylate proteins of apparent Mr 450,000, 180,000, 160,000, 145,000, 135,000, 90,000, 54,000, 51,000, and 20,000, respectively. Some of these phosphorylated polypeptides are in the Mr range of known phosphoproteins involved in excitation-contraction coupling of skeletal muscle, which might give a first hint at the functional importance of the sequential glycolytic reactions compartmentalized in triads. PMID:1731894

  4. Evidence for compartmentalization of mammalian carotenoid metabolism

    PubMed Central

    Palczewski, Grzegorz; Amengual, Jaume; Hoppel, Charles L.; von Lintig, Johannes

    2014-01-01

    The critical role of retinoids (vitamin A and its derivatives) for vision, reproduction, and survival has been well established. Vitamin A is produced from dietary carotenoids such as β-carotene by centric cleavage via the enzyme BCO1. The biochemical and molecular identification of a second structurally related β-carotene metabolizing enzyme, BCO2, has led to a prolonged debate about its relevance in vitamin A biology. While BCO1 cleaves provitamin A carotenoids, BCO2 is more promiscuous and also metabolizes nonprovitamin A carotenoids such as zeaxanthin into long-chain apo-carotenoids. Herein we demonstrate, in cell lines, that human BCO2 is associated with the inner mitochondrial membrane. Different human BCO2 isoforms possess cleavable N-terminal leader sequences critical for mitochondrial import. Subfractionation of murine hepatic mitochondria confirmed the localization of BCO2 to the inner mitochondrial membrane. Studies in BCO2-knockout mice revealed that zeaxanthin accumulates in the inner mitochondrial membrane; in contrast, β-carotene is retained predominantly in the cytoplasm. Thus, we provide evidence for a compartmentalization of carotenoid metabolism that prevents competition between BCO1 and BCO2 for the provitamin and the production of noncanonical β-carotene metabolites.—Palczewski, G., Amengual, J., Hoppel, C. L., von Lintig, J. Evidence for compartmentalization of mammalian carotenoid metabolism. PMID:25002123

  5. A mathematical analysis of second messenger compartmentalization

    NASA Astrophysics Data System (ADS)

    Chen, Wen; Levine, Herbert; Rappel, Wouter-Jan

    2008-12-01

    Intracellular compartmentalization of second messengers can lead to microdomains of elevated concentration that are thought to be involved in ensuring signaling specificity. Most experimental evidence for this compartmentalization involves the second messenger adenosine monophosphate (cAMP), which is degraded by phosphodiesterases (PDEs). One possible way of creating these compartments, supported by recent experiments, is to spatially separate the source of cAMP from regions of elevated PDE concentration. To quantify this possibility, we study here a simplified geometry in two dimensions (2D) and in three dimensions (3D), containing a cAMP point source and regions with different degradation constants. Using the symmetry of our geometry, we are able to derive steady state solutions for the cAMP concentration as a function of the system parameters. Furthermore, we show, using analytics as well as direct numerical simulations, that for physiologically relevant time scales the steady state solution has been reached. Our results indicate that elevating the degradation constant throughout the cell, except for a small microdomain surrounding the source, requires an unphysiologically high cellular PDE concentration. On the other hand, a tight spatial relationship of localized PDEs with the cAMP source can result in functional microdomains while maintaining a physiologically plausible cellular PDE concentration.

  6. Compartmental model of 18F-choline

    NASA Astrophysics Data System (ADS)

    Janzen, T.; Tavola, F.; Giussani, A.; Cantone, M. C.; Uusijärvi, H.; Mattsson, S.; Zankl, M.; Petoussi-Henß, N.; Hoeschen, C.

    2010-03-01

    The MADEIRA Project (Minimizing Activity and Dose with Enhanced Image quality by Radiopharmaceutical Administrations), aims to improve the efficacy and safety of 3D functional imaging by optimizing, among others, the knowledge of the temporal variation of the radiopharmaceuticals' uptake in and clearance from tumor and healthy tissues. With the help of compartmental modeling it is intended to optimize the time schedule for data collection and improve the evaluation of the organ doses to the patients. Administration of 18F-choline to screen for recurrence or the occurrence of metastases in prostate cancer patients is one of the diagnostic applications under consideration in the frame of the project. PET and CT images have been acquired up to four hours after injection of 18F-choline. Additionally blood and urine samples have been collected and measured in a gamma counter. The radioactivity concentration in different organs and data of plasma clearance and elimination into urine were used to set-up a compartmental model of the biokinetics of the radiopharmaceutical. It features a central compartment (blood) exchanging with organs. The structure describes explicitly liver, kidneys, spleen, plasma and bladder as separate units with a forcing function approach. The model is presented together with an evaluation of the individual and population kinetic parameters, and a revised time schedule for data collection is proposed. This optimized time schedule will be validated in a further set of patient studies.

  7. Reactive oxygen species and redox compartmentalization

    PubMed Central

    Kaludercic, Nina; Deshwal, Soni; Di Lisa, Fabio

    2014-01-01

    Reactive oxygen species (ROS) formation and signaling are of major importance and regulate a number of processes in physiological conditions. A disruption in redox status regulation, however, has been associated with numerous pathological conditions. In recent years it has become increasingly clear that oxidative and reductive modifications are confined in a spatio-temporal manner. This makes ROS signaling similar to that of Ca2+ or other second messengers. Some subcellular compartments are more oxidizing (such as lysosomes or peroxisomes) whereas others are more reducing (mitochondria, nuclei). Moreover, although more reducing, mitochondria are especially susceptible to oxidation, most likely due to the high number of exposed thiols present in that compartment. Recent advances in the development of redox probes allow specific measurement of defined ROS in different cellular compartments in intact living cells or organisms. The availability of these tools now allows simultaneous spatio-temporal measurements and correlation between ROS generation and organelle and/or cellular function. The study of ROS compartmentalization and microdomains will help elucidate their role in physiology and disease. Here we will examine redox probes currently available and how ROS generation may vary between subcellular compartments. Furthermore, we will discuss ROS compartmentalization in physiological and pathological conditions focusing our attention on mitochondria, since their vulnerability to oxidative stress is likely at the basis of several diseases. PMID:25161621

  8. Cable properties and compartmentation in Acetabularia.

    PubMed

    Freudling, C; Gradmann, D

    1979-04-01

    The electrical cable properties of three different compartmentation types of Acetabularia cells have been investigated. These three types were: normal cells, 'stumps' (filled with cytoplasm, no central vacuole) and 'tubes' (cytoplasm depleted vacuoles). The latter two types have been obtained by centrifugation of normal cells. Qualitatively, the characteristic biphasic voltage response upon rectangular current pulses is the same in these three types. Quantitatively, however, the two conductances which can be obtained from the biphasic voltage response as well as the apparent capacity of several F . m-2 which derives from the large time constant of the second phase, are drastically increased in stumps and decreased in tubes compared to normal cells. The resting potential is a few mV more negative in stumps, and more positive in tubes, than in normal cells. Based on the existence of the high resting potential and the apparent large capacity in the non-vacuolated stumps, it is concluded that the electrogenic Cl- pump of Acetabularia is located in the plasmalemma membrane and that the apparent large capacity is not a result of the complicated membraneous organisation of the vacuolar system. Several possibilities are discussed, in relation to the quantitative correlation between intracellular compartmentation and electrical membrane parameters.

  9. [Compartmentalization of the cell nucleus and spatial organization of the genome].

    PubMed

    Gavrilov, A A; Razin, S V

    2015-01-01

    The eukaryotic cell nucleus is one of the most complex cell organelles. Despite the absence of membranes, the nuclear space is divided into numerous compartments where different processes in- volved in the genome activity take place. The most important nuclear compartments include nucleoli, nuclear speckles, PML bodies, Cajal bodies, histone locus bodies, Polycomb bodies, insulator bodies, transcription and replication factories. The structural basis for the nuclear compartmentalization is provided by genomic DNA that occupies most of the nuclear volume. Nuclear compartments, in turn, guide the chromosome folding by providing a platform for the spatial interaction of individual genomic loci. In this review, we discuss fundamental principles of higher order genome organization with a focus on chromosome territories and chromosome domains, as well as consider the structure and function of the key nuclear compartments. We show that the func- tional compartmentalization of the cell nucleus and genome spatial organization are tightly interconnected, and that this form of organization is highly dynamic and is based on stochastic processes.

  10. Fasciola hepatica Infection in an Indigenous Community of the Peruvian Jungle.

    PubMed

    Cabada, Miguel M; Castellanos-Gonzalez, Alejandro; Lopez, Martha; Caravedo, María Alejandra; Arque, Eulogia; White, Arthur Clinton

    2016-06-01

    Fasciola hepatica is a zoonotic infection with a worldwide distribution. Autochthonous cases have not been reported in the Amazon region of Peru. Operculated eggs resembling F. hepatica were identified in the stools of five out of 215 subjects in a remote indigenous community of the Peruvian jungle. Polymerase chain reaction targeting Fasciola hepatica cytochrome oxidase subunit 1 (COI) gene and sequencing of the products confirmed Fasciola infection.

  11. Determination of Polycomb Group of Protein Compartmentalization Through Chromatin Fractionation Procedure.

    PubMed

    Marasca, Federica; Marullo, Fabrizia; Lanzuolo, Chiara

    2016-01-01

    Epigenetic mechanisms modulate and maintain the transcriptional state of the genome acting at various levels on chromatin. Emerging findings suggest that the position in the nuclear space and the cross talk between components of the nuclear architecture play a role in the regulation of epigenetic signatures. We recently described a cross talk between the Polycomb group of proteins (PcG) epigenetic repressors and the nuclear lamina. This interplay is important for the maintenance of transcriptional repression at muscle-specific genes and for the correct timing of muscle differentiation. To investigate the synergism between PcG factors and nuclear architecture we improved a chromatin fractionation protocol with the aim to analyze the PcG nuclear compartmentalization. We thus separated PcG proteins in different fractions depending on their solubility. We surprisingly found a consistent amount of PcG proteins in the matrix-associated fraction. In this chapter we describe the chromatin fractionation procedure, a method that can be used to study the nuclear compartmentalization of Polycomb group of proteins and/or PcG targets in murine and Drosophila cells. PMID:27659984

  12. Regulatory T-cell compartmentalization and trafficking

    PubMed Central

    Wei, Shuang; Kryczek, Ilona; Zou, Weiping

    2006-01-01

    CD4+CD25+FOXP3+ regulatory T cells (CD4+ Treg cells) are thought to differentiate in the thymus and immigrate from the thymus to the periphery. Treg cells can regulate both acquired and innate immunity through multiple modes of suppression. The cross-talk between Treg cells and targeted cells, such as antigen-presenting cells (APCs) and T cells, is crucial for ensuring suppression by Treg cells in the appropriate microenvironment. Emerging evidence suggests that Treg compartmentalization and trafficking may be tissue or/and organ specific and that distinct chemokine receptor and integrin expression may contribute to selective retention and trafficking of Treg cells at sites where regulation is required. In this review, the cellular and molecular signals that control specialized migration and retention of Treg cells are discussed. PMID:16537800

  13. Fractional kinetics in multi-compartmental systems.

    PubMed

    Dokoumetzidis, Aristides; Magin, Richard; Macheras, Panos

    2010-10-01

    Fractional calculus, the branch of calculus dealing with derivatives of non-integer order (e.g., the half-derivative) allows the formulation of fractional differential equations (FDEs), which have recently been applied to pharmacokinetics (PK) for one-compartment models. In this work we extend that theory to multi-compartmental models. Unlike systems defined by a single ordinary differential equation (ODE), considering fractional multi-compartmental models is not as simple as changing the order of the ordinary derivatives of the left-hand side of the ODEs to fractional orders. The latter may produce inconsistent systems which violate mass balance. We present a rationale for fractionalization of ODEs, which produces consistent systems and allows processes of different fractional orders in the same system. We also apply a method of solving such systems based on a numerical inverse Laplace transform algorithm, which we demonstrate that is consistent with analytical solutions when these are available. As examples of our approach, we consider two cases of a basic two-compartment PK model with a single IV dose and multiple oral dosing, where the transfer from the peripheral to the central compartment is of fractional order α < 1, accounting for anomalous kinetics and deep tissue trapping, while all other processes are of the usual order 1. Simulations with the studied systems are performed using the numerical inverse Laplace transform method. It is shown that the presence of a transfer rate of fractional order produces a non-exponential terminal phase, while multiple dose and constant infusion systems never reach steady state and drug accumulation carries on indefinitely. The IV fractional system is also fitted to PK data and parameter values are estimated. In conclusion, our approach allows the formulation of systems of FDEs, mixing different fractional orders, in a consistent manner and also provides a method for the numerical solution of these systems. PMID

  14. Field Testing of Compartmentalization Methods for Multifamily Construction

    SciTech Connect

    Ueno, K.; Lstiburek, J. W.

    2015-03-01

    The 2012 International Energy Conservation Code (IECC) has an airtightness requirement of 3 air changes per hour at 50 Pascals test pressure (3 ACH50) for single-family and multifamily construction (in climate zones 3–8). The Leadership in Energy & Environmental Design certification program and ASHRAE Standard 189 have comparable compartmentalization requirements. ASHRAE Standard 62.2 will soon be responsible for all multifamily ventilation requirements (low rise and high rise); it has an exceptionally stringent compartmentalization requirement. These code and program requirements are driving the need for easier and more effective methods of compartmentalization in multifamily buildings.

  15. Calcium dynamics and compartmentalization in leech neurons.

    PubMed

    Andjelic, Sofija; Torre, Vincent

    2005-12-01

    Calcium dynamics in leech neurons were studied using a fast CCD camera. Fluorescence changes (DeltaF/F) of the membrane impermeable calcium indicator Oregon Green were measured. The dye was pressure injected into the soma of neurons under investigation. DeltaF/F caused by a single action potential (AP) in mechanosensory neurons had approximately the same amplitude and time course in the soma and in distal processes. By contrast, in other neurons such as the Anterior Pagoda neuron, the Annulus Erector motoneuron, the L motoneuron, and other motoneurons, APs evoked by passing depolarizing current in the soma produced much larger fluorescence changes in distal processes than in the soma. When APs were evoked by stimulating one distal axon through the root, DeltaF/F was large in all distal processes but very small in the soma. Our results show a clear compartmentalization of calcium dynamics in most leech neurons in which the soma does not give propagating action potentials. In such cells, the soma, while not excitable, can affect information processing by modulating the sites of origin and conduction of AP propagation in distal excitable processes.

  16. Compartmentalization and Transport in Synthetic Vesicles

    PubMed Central

    Schmitt, Christine; Lippert, Anna H.; Bonakdar, Navid; Sandoghdar, Vahid; Voll, Lars M.

    2016-01-01

    Nanoscale vesicles have become a popular tool in life sciences. Besides liposomes that are generated from phospholipids of natural origin, polymersomes fabricated of synthetic block copolymers enjoy increasing popularity, as they represent more versatile membrane building blocks that can be selected based on their specific physicochemical properties, such as permeability, stability, or chemical reactivity. In this review, we focus on the application of simple and nested artificial vesicles in synthetic biology. First, we provide an introduction into the utilization of multicompartmented vesosomes as compartmentalized nanoscale bioreactors. In the bottom-up development of protocells from vesicular nanoreactors, the specific exchange of pathway intermediates across compartment boundaries represents a bottleneck for future studies. To date, most compartmented bioreactors rely on unspecific exchange of substrates and products. This is either based on changes in permeability of the coblock polymer shell by physicochemical triggers or by the incorporation of unspecific porin proteins into the vesicle membrane. Since the incorporation of membrane transport proteins into simple and nested artificial vesicles offers the potential for specific exchange of substances between subcompartments, it opens new vistas in the design of protocells. Therefore, we devote the main part of the review to summarize the technical advances in the use of phospholipids and block copolymers for the reconstitution of membrane proteins. PMID:26973834

  17. Compartmentalized Cytokine Responses in Hidradenitis Suppurativa

    PubMed Central

    Savva, Athina; Kersten, Brigit; Pistiki, Aikaterini; van de Veerdonk, Frank L.; Netea, Mihai G.; van der Meer, Jos W.; Giamarellos-Bourboulis, Evangelos J.

    2015-01-01

    Background Favorable treatment outcomes with TNF blockade led us to explore cytokine responses in hidradenitis suppurativa (HS). Methods Blood monocytes of 120 patients and 24 healthy volunteers were subtyped by flow cytometry. Isolated blood mononuclear cells (PBMCs) were stimulated for cytokine production; this was repeated in 13 severe patients during treatment with etanercept. Cytokines in pus were measured. Results CD14brightCD16dim inflammatory monocytes and patrolling monocytes were increased in Hurley III patients. Cytokine production by stimulated PBMCs was low compared to controls but the cytokine gene copies did not differ, indicating post-translational inhibition. The low production of IL-17 was restored, when cells were incubated with adalimumab. In pus, high concentrations of pro-inflammatory cytokines were detected. Based on the patterns, six different cytokine profiles were discerned, which are potentially relevant for the choice of treatment. Clinical improvement with etanercept was predicted by increased production of IL-1β and IL-17 by PBMCs at week 8. Conclusions Findings indicate compartmentalized cytokine expression in HS; high in pus but suppressed in PBMCs. This is modulated through blockade of TNF. PMID:26091259

  18. Evolutionary origins of metabolic compartmentalization in eukaryotes

    PubMed Central

    Martin, William

    2010-01-01

    Many genes in eukaryotes are acquisitions from the free-living antecedents of chloroplasts and mitochondria. But there is no evolutionary ‘homing device’ that automatically directs the protein product of a transferred gene back to the organelle of its provenance. Instead, the products of genes acquired from endosymbionts can explore all targeting possibilities within the cell. They often replace pre-existing host genes, or even whole pathways. But the transfer of an enzymatic pathway from one compartment to another poses severe problems: over evolutionary time, the enzymes of the pathway acquire their targeting signals for the new compartment individually, not in unison. Until the whole pathway is established in the new compartment, newly routed individual enzymes are useless, and their genes will be lost through mutation. Here it is suggested that pathways attain novel compartmentation variants via a ‘minor mistargeting’ mechanism. If protein targeting in eukaryotic cells possesses enough imperfection such that small amounts of entire pathways continuously enter novel compartments, selectable units of biochemical function would exist in new compartments, and the genes could become selected. Dual-targeting of proteins is indeed very common within eukaryotic cells, suggesting that targeting variation required for this minor mistargeting mechanism to operate exists in nature. PMID:20124349

  19. Subcellular compartmentation of ascorbate and its variation in disease states.

    PubMed

    Bánhegyi, Gábor; Benedetti, Angelo; Margittai, Eva; Marcolongo, Paola; Fulceri, Rosella; Németh, Csilla E; Szarka, András

    2014-09-01

    Beyond its general role as antioxidant, specific functions of ascorbate are compartmentalized within the eukaryotic cell. The list of organelle-specific functions of ascorbate has been recently expanded with the epigenetic role exerted as a cofactor for DNA and histone demethylases in the nucleus. Compartmentation necessitates the transport through intracellular membranes; members of the GLUT family and sodium-vitamin C cotransporters mediate the permeation of dehydroascorbic acid and ascorbate, respectively. Recent observations show that increased consumption and/or hindered entrance of ascorbate in/to a compartment results in pathological alterations partially resembling to scurvy, thus diseases of ascorbate compartmentation can exist. The review focuses on the reactions and transporters that can modulate ascorbate concentration and redox state in three compartments: endoplasmic reticulum, mitochondria and nucleus. By introducing the relevant experimental and clinical findings we make an attempt to coin the term of ascorbate compartmentation disease. PMID:24907663

  20. Holocene cultural history of Red jungle fowl (Gallus gallus) and its domestic descendant in East Asia

    NASA Astrophysics Data System (ADS)

    Peters, Joris; Lebrasseur, Ophélie; Deng, Hui; Larson, Greger

    2016-06-01

    Nearly three decades ago, zooarchaeologists postulated that chicken husbandry was practiced in Northern China by ∼8.0 ka calBP. Recently, ancient mitogenome analyses of galliform remains suggested that Red jungle fowl (Gallus gallus) was already present in the Yellow River basin several millennia earlier, shortly after the onset of the Holocene. If these conclusions are correct, the origins of chicken domestication and husbandry in the region may have been spurred by agricultural innovations in the lower Yellow River basin including millet cultivation, pig husbandry, and dog breeding. In addition, the dispersal of poultry farming from East Asia to Asia Minor and Europe could therefore date to the Neolithic along ancient trade routes across Central Asia rather than via South Asia and Mesopotamia. For this scenario to be plausible, the post-Pleistocene climatic conditions must have been favourable to allow for a northward extension of the native distribution of tropical Red jungle fowl currently not found north of ∼25°N. This study combines Holocene palaeoclimate and archaeofaunal archives with new zooarchaeological insights alongside a discussion of methodological issues and cultural aspects in order to revisit the hypothesis of an early Holocene Gallus domestication and Neolithic poultry husbandry in Northern China. Our results regarding the natural and cultural history of Red jungle fowl and domestic chickens in East Asia, and the timing of chicken dispersal across the Old World suggest that an early Holocene domestication of chickens is problematic at best. We conclude by postulating an alternative model for the early exploitation of a key domestic species in present-day East Asia.

  1. Renormalization-Group Theory Study of Superfluidity and Phase Separation of Helium Mixtures Immersed in Jungle-Gym Aerogel

    NASA Astrophysics Data System (ADS)

    Lopatnikova, Anna; Berker, A. Nihat

    1997-03-01

    Superfluidity and phase separation in ^3He-^4He mixtures immersed in jungle-gym (non-random) aerogel are studied by renormalization-group theory.(Phys. Rev. B, in press (1996)) Phase diagrams are calculated for a variety of aerogel concentrations. Superfluidity at very low ^4He concentrations and a depressed tricritical temperature are found at the onset of superfluidity. A superfluid-superfluid phase separation, terminating at an isolated critical point, is found entirely within the superfluid phase. These phenomena, and trends with respect to aerogel concentration, are explained by the connectivity and tenuousness of jungle-gym aerogel.

  2. Digital processing of satellite imagery application to jungle areas of Peru

    NASA Technical Reports Server (NTRS)

    Pomalaza, J. C. (Principal Investigator); Pomalaza, C. A.; Espinoza, J.

    1976-01-01

    The author has identified the following significant results. The use of clustering methods permits the development of relatively fast classification algorithms that could be implemented in an inexpensive computer system with limited amount of memory. Analysis of CCTs using these techniques can provide a great deal of detail permitting the use of the maximum resolution of LANDSAT imagery. Potential cases were detected in which the use of other techniques for classification using a Gaussian approximation for the distribution functions can be used with advantage. For jungle areas, channels 5 and 7 can provide enough information to delineate drainage patterns, swamp and wet areas, and make a reasonable broad classification of forest types.

  3. Jungle yellow fever: clinical and laboratorial studies emphasizing viremia on a human case.

    PubMed

    Nassar, E da S; Chamelet, E L; Coimbra, T L; de Souza, L T; Suzuki, A; Ferreira, I B; da Silva, M V; Rocco, I M; Travassos da Rosa, A P

    1995-01-01

    The authors report the clinical, laboratorial and epidemiological aspects of a human case of jungle yellow fever. The patient suffered from fever, chills, sweating, headaches, backaches, myalgia, epigastric pains, nausea, vomiting, diarrhea and prostration. He was unvaccinated and had been working in areas where cases of jungle yellow fever had been confirmed. Investigations concerning the yellow fever virus were performed. Blood samples were collected on several days in the course of the illness. Three of these samples (those obtained on days 5, 7 and 10) were inoculated into suckling mice in attempt to isolate virus and to titrate the viremia level. Serological surveys were carried out by using the IgM Antibodies Capture Enzyme Linked Immunosorbent Assay (MAC-ELISA), Complement Fixation (CF), Hemagglutination Inhibition (HI) and Neutralization (N) tests. The yellow fever virus, recovered from the two first samples and the virus titration, showed high level of viremia. After that, specific antibodies appeared in all samples. The interval between the end of the viremia and the appearance of the antibodies was associated with the worsening of clinical symptoms, including bleeding of the mucous membrane. One must be aware of the risk of having a urban epidemics in areas where Aedes aegypti is found in high infestation indexes.

  4. Compartmentalization of prostaglandins in the canine kidney

    SciTech Connect

    Morgan-Boyd, R.L.

    1986-01-01

    The kidney has been shown to synthesize all of the naturally occurring major prostaglandins which may be restricted to a discrete part of the kidney where their actions are physiologically important, such as the vascular compartment and the tubular compartment. In order to examine this concept of compartmentalization, the authors conducted a series of experiments to determine whether PGl/sub 2/, measured as 6-keto-pGF/sub 1..cap alpha../, produced in the kidney is restricted to the renal vascular compartment or whether it also has access to the tubular compartment. Experiments were performed in the pentobarbital-anesthetized dog. Increasing pre-glomerular levels of 6-keto-PFG/sub 1..cap alpha../ caused marked increases in both the urinary excretion and the renal venous outflow to 6-keto-PGF/sub 1..cap alpha../. When /sup 3/H-6-keto-PGF/sub 1..cap alpha../ was co-infused with inulin into the renal artery, 33% of the radioactivity and 23% of the inulin was recovered on first pass. With infusion of /sup 3/H-PGl/sub 2/ and inulin, 20% of the radioactivity and 28% of the inulin reached the urine on first pass. Radioactive PGl/sub 2/ appeared to be less filterable at the glomeruli than either /sup 3/H-6-keto-PGF/sub 1..cap alpha../ or inulin. In the final set of experiments, in which dogs were prepared for a ureteral stopped-flow study, the PGE/sub 2//U/P/sub In/ ratio a peak was observed proximal to the Na/sup +/ plateau but distal to the Na+ nadir. In light of the results from the stopped-flow study and the intrarenal infusion studies, they conclude that PGE/sub 2/ synthesized in the kidney enters both the renal and tubular compartments. In contrast, they find that 6-keto-PGF/sub 1..cap alpha../ of renal origin enters only the renal origin enters only the renal vascular compartment and not the tubular compartment.

  5. Towards repurposing the yeast peroxisome for compartmentalizing heterologous metabolic pathways

    DOE PAGES

    DeLoache, William C.; Russ, Zachary N.; Dueber, John E.

    2016-03-30

    Compartmentalization of enzymes into organelles is a promising strategy for limiting metabolic crosstalk and improving pathway efficiency, but improved tools and design rules are needed to make this strategy available to more engineered pathways. Here we focus on the Saccharomyces cerevisiae peroxisome and develop a sensitive high-throughput assay for peroxisomal cargo import. We identify an enhanced peroxisomal targeting signal type 1 (PTS1) for rapidly sequestering non-native cargo proteins. Additionally, we perform the first systematic in vivo measurements of nonspecific metabolite permeability across the peroxisomal membrane using a polymer exclusion assay. Finally, we apply these new insights to compartmentalize a two-enzymemore » pathway in the peroxisome and characterize the expression regimes where compartmentalization leads to improved product titre. Lastly, this work builds a foundation for using the peroxisome as a synthetic organelle, highlighting both promise and future challenges on the way to realizing this goal.« less

  6. Towards repurposing the yeast peroxisome for compartmentalizing heterologous metabolic pathways.

    PubMed

    DeLoache, William C; Russ, Zachary N; Dueber, John E

    2016-03-30

    Compartmentalization of enzymes into organelles is a promising strategy for limiting metabolic crosstalk and improving pathway efficiency, but improved tools and design rules are needed to make this strategy available to more engineered pathways. Here we focus on the Saccharomyces cerevisiae peroxisome and develop a sensitive high-throughput assay for peroxisomal cargo import. We identify an enhanced peroxisomal targeting signal type 1 (PTS1) for rapidly sequestering non-native cargo proteins. Additionally, we perform the first systematic in vivo measurements of nonspecific metabolite permeability across the peroxisomal membrane using a polymer exclusion assay. Finally, we apply these new insights to compartmentalize a two-enzyme pathway in the peroxisome and characterize the expression regimes where compartmentalization leads to improved product titre. This work builds a foundation for using the peroxisome as a synthetic organelle, highlighting both promise and future challenges on the way to realizing this goal.

  7. Modeling the Kinetics of a Memory-Associated Immediate Early Gene's Compartmental Expression After Sensory Experience

    NASA Astrophysics Data System (ADS)

    Willats, Adam; Ivanova, Tamara; Prinz, Astrid; Liu, Robert

    2015-03-01

    Immediate Early Genes (IEGs) are rapidly and transiently transcribed in neurons after a sensory experience. Some of these genes act as effector IEGs, which mediate specific effects on cellular function. Arc is one such effector IEG that is essential for synaptic plasticity and memory consolidation in hippocampus and cortex. The expression of Arc in neurons has previously been examined using an imaging method known as Compartmental Analysis of Temporal Fluorescent In-Situ Hybridization. Previous work found that the time course of Arc expression within the nuclear and perinuclear cytoplasmic compartments of a neuron is altered by prior sensory experience. We explore a simple model of the kinetics of IEG transcription and nuclear export, with the aim of eventually uncovering possible mechanisms for how experience alters expression kinetics. Thus far, we characterize our compartmental model using phase-plane analysis and validate it against several IEG expression data sets, including one where prior experience with vocalizing mice alters the time course of call-induced Arc expression in the auditory cortex of a listening mouse. Our model provides a framework to explore why Arc expression may change depending on a receiver's past sound experience and internal state. Adam Willats was supported by NIH Training Grant 5T90DA032466. This research was also supported by NIDCD R01 DC8343.

  8. Evidence of recent jungle yellow-fever activity in eastern Panama*

    PubMed Central

    Galindo, Pedro; Srihongse, Sunthorn

    1967-01-01

    Outbreaks of jungle yellow fever in man have been recorded twice from eastern Panama of recent years, first in 1948 and again in 1956. Since then, a close surveillance has been maintained on virus activity in eastern Panama. Recent field observations and serological tests on 402 monkey sera indicate that there was an outbreak of yellow fever among monkeys of southern Darién Province some time between 1963 and 1965. It does not appear that the outbreak has spread as yet to other areas. Virus transmission may have been permanently disrupted during the drought which affected the region in 1965. However, if the virus had managed to survive this unfavourable period, an epizootic wave might have evolved, invading forested areas immediately east of the Panama Canal, now inhabited by a dense non-immune human population. PMID:4962725

  9. Barriers in the brain: resolving dendritic spine morphology and compartmentalization

    PubMed Central

    Adrian, Max; Kusters, Remy; Wierenga, Corette J.; Storm, Cornelis; Hoogenraad, Casper C.; Kapitein, Lukas C.

    2014-01-01

    Dendritic spines are micron-sized protrusions that harbor the majority of excitatory synapses in the central nervous system. The head of the spine is connected to the dendritic shaft by a 50–400 nm thin membrane tube, called the spine neck, which has been hypothesized to confine biochemical and electric signals within the spine compartment. Such compartmentalization could minimize interspinal crosstalk and thereby support spine-specific synapse plasticity. However, to what extent compartmentalization is governed by spine morphology, and in particular the diameter of the spine neck, has remained unresolved. Here, we review recent advances in tool development – both experimental and theoretical – that facilitate studying the role of the spine neck in compartmentalization. Special emphasis is given to recent advances in microscopy methods and quantitative modeling applications as we discuss compartmentalization of biochemical signals, membrane receptors and electrical signals in spines. Multidisciplinary approaches should help to answer how dendritic spine architecture affects the cellular and molecular processes required for synapse maintenance and modulation. PMID:25538570

  10. Shared and Distinct Mechanisms of Compartmentalized and Cytosolic Ciliogenesis.

    PubMed

    Avidor-Reiss, Tomer; Leroux, Michel R

    2015-12-01

    Most motile and all non-motile (also known as primary) eukaryotic cilia possess microtubule-based axonemes that are assembled at the cell surface to form hair-like or more elaborate compartments endowed with motility and/or signaling functions. Such compartmentalized ciliogenesis depends on the core intraflagellar transport (IFT) machinery and the associated Bardet-Biedl syndrome complex (BBSome) for dynamic delivery of ciliary components. The transition zone (TZ), an ultrastructurally complex barrier or 'gate' at the base of cilia, also contributes to the formation of compartmentalized cilia. Yet, some ciliated protists do not have IFT components and, like some metazoan spermatozoa, use IFT-independent mechanisms to build axonemes exposed to the cytosol. Moreover, various ciliated protists lack TZ components, whereas Drosophila sperm surprisingly requires the activity of dynamically localized TZ proteins for cytosolic ciliogenesis. Here, we discuss the various ways eukaryotes use IFT and/or TZ proteins to generate the wide assortment of compartmentalized and cytosolic cilia observed in nature. Consideration of the different ciliogenesis pathways allows us to propose how three types of cytosol-exposed cilia (primary, secondary and tertiary), including cilia found in the human sperm proximal segment, are likely generated by evolutionary derivations of compartmentalized ciliogenesis.

  11. Compartmentalization of Gd liposomes: the quenching effect explained.

    PubMed

    Guenoun, Jamal; Doeswijk, Gabriela N; Krestin, Gabriel P; Bernsen, Monique R

    2016-01-01

    Cationic liposomes carrying high [Gd] can be used as efficient cell-labeling agents. In a compartmentalized state, Gd can cause signal loss (relaxivity quenching). The contributions of liposomal [Gd], size and compartmentalization state to relaxivity quenching were assessed. The dependency of signal intensity (SI) on intraliposomal [Gd] was assessed comparing three different [Gd] (0.3, 0.6 and 1.0 M Gd) in both small (80 nm) and large (120 nm) cationic liposomes. In addition, five compartmentalization states were compared: free Gd, intact Gd liposomes, ruptured Gd liposomes, Gd liposomes in intact cells and Gd liposomes in ruptured cells (simulating cell death). Gd also causes R2 effects, which is often overlooked. Therefore, both R1 and R2 relaxation rates of a dilution range were measured by T1 and T2 mapping on a 7 T clinical scanner. Less is more. As the unidirectional water efflux rate (outbound across the liposome membrane, κle) is proportional to the surface:volume ratio, smaller liposomes yielded a consistently higher R1 than larger liposomes. For equal voxel [Gd] less concentrated liposomes (0.3 M Gd) yielded higher R1/R2 ratio because of the higher extraliposomal water fraction (vl ). Gd exhibits a dualistic behavior: from hypointensity to hyperintensity to hypointensity, with decreasing [Gd]. Regarding compartmentalization, fewer membrane barriers means a higher R1 /R2 ratio. Gd liposomes exhibit a versatile contrast behavior, dependent on the compartmentalization state, liposomal size, intraliposomal [Gd] and liposome number. Both R1 and R2 effects contribute to this. The versatility allows one to tailor the optimal liposomal formulation to desired goals in cell labeling and tracking.

  12. Continuing pollution from the Rum Jungle U-Cu project: a critical evaluation of environmental monitoring and rehabilitation.

    PubMed

    Mudd, Gavin M; Patterson, James

    2010-05-01

    The former Rum Jungle uranium-copper project, Australia, is an internationally important case study on environmental pollution from and rehabilitation of mining. The Rum Jungle mining project is briefly reviewed, followed by a critical evaluation of monitoring data and pollution loads prior to and after rehabilitation - leading to the conclusion that rehabilitation has clearly failed the test of time after just two decades. The most critical findings are the need to understand pollution cycles holistically, and designing monitoring regimes to match, explicit inclusion of radiological criteria (lacking in original planning), and finally the need to set targets based on environmental criteria. Two examples include polluted groundwater which was excluded from rehabilitation and the poor design, construction and/or performance of engineered soil covers - both leading to increasing acid drainage impacts on the Finniss River. The critical review therefore presents a valuable case study of the environmental performance of uranium mine site rehabilitation.

  13. The epidemiology of dengue virus infection among urban, jungle, and rural populations in the Amazon region of Peru.

    PubMed

    Hayes, C G; Phillips, I A; Callahan, J D; Griebenow, W F; Hyams, K C; Wu, S J; Watts, D M

    1996-10-01

    The first confirmed outbreak of dengue fever in Peru occurred during 1990 in Iquitos, a city of approximately 300,000 residents in the Amazon region. Because of the apparent establishment of endemic transmission of this mosquito-borne viral disease following the outbreak, epidemiologic studies were initiated in 1992. Blood specimens and data on demographic, environmental, and medical history factors were collected from volunteers in an urban sector of Iquitos, in a rural area on the outskirts of Iquitos, and in three nearby jungle communities. A follow-up blood specimen was obtained approximately one year later from a sample of subjects. Sera were tested for dengue IgG antibody by an enzyme-linked immunosorbent assay, and specificity was verified using a plaque-reduction neutralization test. Dengue antibody prevalence was 66% in the urban population, 26% in the rural population, and 32-67% in the three jungle areas. A significant association was found between age and antibody prevalence, with a steady increase in prevalence from 18% among subjects less than five years of age to greater than 90% for subjects more than 50 years old. Increased antibody prevalence also was associated with urban and jungle residence and with a piped source of household drinking water. Seroconversions were documented in four of five surveyed communities. These results indicate that dengue virus transmission continues in and around Iquitos and suggest that transmission also occurred prior to the 1990 epidemic.

  14. Quasi-steady state reduction for compartmental systems

    NASA Astrophysics Data System (ADS)

    Goeke, Alexandra; Lax, Christian

    2016-07-01

    We present a method to determine an asymptotic reduction (in the sense of Tikhonov and Fenichel) for singularly perturbed compartmental systems in the presence of slow transport. It turns out that the reduction can be derived from the individual interaction terms alone. We apply the result to spatially discretized reaction-diffusion systems and obtain (based on the reduced discretized systems) a heuristic to reduce reaction-diffusion systems in presence of slow diffusion.

  15. Compartmentation of glycogen metabolism revealed from 13C isotopologue distributions

    PubMed Central

    2011-01-01

    Background Stable isotope tracers are used to assess metabolic flux profiles in living cells. The existing methods of measurement average out the isotopic isomer distribution in metabolites throughout the cell, whereas the knowledge of compartmental organization of analyzed pathways is crucial for the evaluation of true fluxes. That is why we accepted a challenge to create a software tool that allows deciphering the compartmentation of metabolites based on the analysis of average isotopic isomer distribution. Results The software Isodyn, which simulates the dynamics of isotopic isomer distribution in central metabolic pathways, was supplemented by algorithms facilitating the transition between various analyzed metabolic schemes, and by the tools for model discrimination. It simulated 13C isotope distributions in glucose, lactate, glutamate and glycogen, measured by mass spectrometry after incubation of hepatocytes in the presence of only labeled glucose or glucose and lactate together (with label either in glucose or lactate). The simulations assumed either a single intracellular hexose phosphate pool, or also channeling of hexose phosphates resulting in a different isotopic composition of glycogen. Model discrimination test was applied to check the consistency of both models with experimental data. Metabolic flux profiles, evaluated with the accepted model that assumes channeling, revealed the range of changes in metabolic fluxes in liver cells. Conclusions The analysis of compartmentation of metabolic networks based on the measured 13C distribution was included in Isodyn as a routine procedure. The advantage of this implementation is that, being a part of evaluation of metabolic fluxes, it does not require additional experiments to study metabolic compartmentation. The analysis of experimental data revealed that the distribution of measured 13C-labeled glucose metabolites is inconsistent with the idea of perfect mixing of hexose phosphates in cytosol. In contrast

  16. Fractional two-compartmental model for articaine serum levels

    NASA Astrophysics Data System (ADS)

    Petronijevic, Branislava; Sarcev, Ivan; Zorica, Dusan; Janev, Marko; Atanackovic, Teodor M.

    2016-06-01

    Two fractional two-compartmental models are applied to the pharmacokinetics of articaine. Integer order derivatives are replaced by fractional derivatives, either of different, or of same orders. Models are formulated so that the mass balance is preserved. Explicit forms of the solutions are obtained in terms of the Mittag-Leffler functions. Pharmacokinetic parameters are determined by the use of the evolutionary algorithm and trust regions optimization to recover the experimental data.

  17. Field Testing of Compartmentalization Methods for Multifamily Construction

    SciTech Connect

    Ueno, K.; Lstiburek, J.

    2015-03-01

    The 2012 IECC has an airtightness requirement of 3 air changes per hour at 50 Pascals test pressure for both single-family and multifamily construction in Climate Zones 3-8. Other programs (LEED, ASHRAE 189, ASHRAE 62.2) have similar or tighter compartmentalization requirements, driving the need for easier and more effective methods of compartmentalization in multifamily buildings. Builders and practitioners have found that fire-resistance rated wall assemblies are a major source of difficulty in air sealing/compartmentalization, particularly in townhouse construction. This problem is exacerbated when garages are “tucked in” to the units and living space is located over the garages. In this project, Building Science Corporation examined the taping of exterior sheathing details to improve air sealing results in townhouse and multifamily construction, when coupled with a better understanding of air leakage pathways. Current approaches are cumbersome, expensive, time consuming, and ineffective; these details were proposed as a more effective and efficient method. The effectiveness of these air sealing methods was tested with blower door testing, including “nulled” or “guarded” testing (adjacent units run at equal test pressure to null out inter-unit air leakage, or “pressure neutralization”). Pressure diagnostics were used to evaluate unit-to-unit connections and series leakage pathways (i.e., air leakage from exterior, into the fire-resistance rated wall assembly, and to the interior).

  18. Cross-membranes orchestrate compartmentalization and morphogenesis in Streptomyces

    PubMed Central

    Celler, Katherine; Koning, Roman I.; Willemse, Joost; Koster, Abraham J.; van Wezel, Gilles P.

    2016-01-01

    Far from being simple unicellular entities, bacteria have complex social behaviour and organization, living in large populations, and some even as coherent, multicellular entities. The filamentous streptomycetes epitomize such multicellularity, growing as a syncytial mycelium with physiologically distinct hyphal compartments separated by infrequent cross-walls. The viability of mutants devoid of cell division, which can be propagated from fragments, suggests the presence of a different form of compartmentalization in the mycelium. Here we show that complex membranes, visualized by cryo-correlative light microscopy and electron tomography, fulfil this role. Membranes form small assemblies between the cell wall and cytoplasmic membrane, or, as evidenced by FRAP experiments, large protein-impermeable cross-membrane structures, which compartmentalize the multinucleoid mycelium. All areas containing cross-membrane structures are nucleoid-restricted zones, suggesting that the membrane assemblies may also act to protect nucleoids from cell-wall restructuring events. Our work reveals a novel mechanism of controlling compartmentalization and development in multicellular bacteria. PMID:27291257

  19. Cross-membranes orchestrate compartmentalization and morphogenesis in Streptomyces.

    PubMed

    Celler, Katherine; Koning, Roman I; Willemse, Joost; Koster, Abraham J; van Wezel, Gilles P

    2016-01-01

    Far from being simple unicellular entities, bacteria have complex social behaviour and organization, living in large populations, and some even as coherent, multicellular entities. The filamentous streptomycetes epitomize such multicellularity, growing as a syncytial mycelium with physiologically distinct hyphal compartments separated by infrequent cross-walls. The viability of mutants devoid of cell division, which can be propagated from fragments, suggests the presence of a different form of compartmentalization in the mycelium. Here we show that complex membranes, visualized by cryo-correlative light microscopy and electron tomography, fulfil this role. Membranes form small assemblies between the cell wall and cytoplasmic membrane, or, as evidenced by FRAP experiments, large protein-impermeable cross-membrane structures, which compartmentalize the multinucleoid mycelium. All areas containing cross-membrane structures are nucleoid-restricted zones, suggesting that the membrane assemblies may also act to protect nucleoids from cell-wall restructuring events. Our work reveals a novel mechanism of controlling compartmentalization and development in multicellular bacteria. PMID:27291257

  20. Digital PCR on an integrated self-priming compartmentalization chip.

    PubMed

    Zhu, Qiangyuan; Qiu, Lin; Yu, Bingwen; Xu, Yanan; Gao, Yibo; Pan, Tingting; Tian, Qingchang; Song, Qi; Jin, Wei; Jin, Qinhan; Mu, Ying

    2014-03-21

    An integrated on-chip valve-free and power-free microfluidic digital PCR device is for the first time developed by making use of a novel self-priming compartmentalization and simple dehydration control to realize 'divide and conquer' for single DNA molecule detection. The high gas solubility of PDMS is exploited to provide the built-in power of self-priming so that the sample and oil are sequentially sucked into the device to realize sample self-compartmentalization based on surface tension. The lifespan of its self-priming capability was about two weeks tested using an air-tight packaging bottle sealed with a small amount of petroleum jelly, which is significant for a practical platform. The SPC chip contains 5120 independent 5 nL microchambers, allowing the samples to be compartmentalized completely. Using this platform, three different abundances of lung cancer related genes are detected to demonstrate the feasibility and flexibility of the microchip for amplifying a single nucleic acid molecule. For maximal accuracy, within less than 5% of the measurement deviation, the optimal number of positive chambers is between 400 and 1250 evaluated by the Poisson distribution, which means one panel can detect an average of 480 to 4804 template molecules. This device without world-to-chip connections eliminates the constraint of the complex pipeline control, and is an integrated on-chip platform, which would be a significant improvement to digital PCR automation and more user-friendly.

  1. Rewiring and regulation of cross-compartmentalized metabolism in protists.

    PubMed

    Ginger, Michael L; McFadden, Geoffrey I; Michels, Paul A M

    2010-03-12

    Plastid acquisition, endosymbiotic associations, lateral gene transfer, organelle degeneracy or even organelle loss influence metabolic capabilities in many different protists. Thus, metabolic diversity is sculpted through the gain of new metabolic functions and moderation or loss of pathways that are often essential in the majority of eukaryotes. What is perhaps less apparent to the casual observer is that the sub-compartmentalization of ubiquitous pathways has been repeatedly remodelled during eukaryotic evolution, and the textbook pictures of intermediary metabolism established for animals, yeast and plants are not conserved in many protists. Moreover, metabolic remodelling can strongly influence the regulatory mechanisms that control carbon flux through the major metabolic pathways. Here, we provide an overview of how core metabolism has been reorganized in various unicellular eukaryotes, focusing in particular on one near universal catabolic pathway (glycolysis) and one ancient anabolic pathway (isoprenoid biosynthesis). For the example of isoprenoid biosynthesis, the compartmentalization of this process in protists often appears to have been influenced by plastid acquisition and loss, whereas for glycolysis several unexpected modes of compartmentalization have emerged. Significantly, the example of trypanosomatid glycolysis illustrates nicely how mathematical modelling and systems biology can be used to uncover or understand novel modes of pathway regulation.

  2. Compartmentalized Droplets for Continuous Flow Liquid-Liquid Interface Catalysis.

    PubMed

    Zhang, Ming; Wei, Lijuan; Chen, Huan; Du, Zhiping; Binks, Bernard P; Yang, Hengquan

    2016-08-17

    To address the limitations of batch organic-aqueous biphasic catalysis, we develop a conceptually novel method termed Flow Pickering Emulsion, or FPE, to process biphasic reactions in a continuous flow fashion. This method involves the compartmentalization of bulk water into micron-sized droplets based on a water-in-oil Pickering emulsion, which are packed into a column reactor. The compartmentalized water droplets can confine water-soluble catalysts, thus "immobilizing" the catalyst in the column reactor, while the interstices between the droplets allow the organic (oil) phase to flow. Key fundamental principles underpinning this method such as the oil phase flow behavior, the stability of compartmentalized droplets and the confinement capability of these droplets toward water-soluble catalysts are experimentally and theoretically investigated. As a proof of this concept, case studies including a sulfuric acid-catalyzed addition reaction, a heteropolyacid-catalyzed ring opening reaction and an enzyme-catalyzed chiral reaction demonstrate the generality and versatility of the FPE method. Impressively, in addition to the excellent durability, the developed FPE reactions exhibit up to 10-fold reaction efficiency enhancement in comparison to the existing batch reactions, indicating a unique flow interface catalysis effect. This study opens up a new avenue to allow conventional biphasic catalysis reactions to access more sustainable and efficient flow chemistry using an innovative liquid-liquid interface protocol. PMID:27429173

  3. Comparative phylogeography of two crow species: jungle crow Corvus macrorhynchos and carrion crow Corvus corone.

    PubMed

    Kryukov, Alexey; Spiridonova, Liudmila; Nakamura, Sumio; Haring, Elisabeth; Suzuki, Hitoshi

    2012-08-01

    The jungle crow Corvus macrorhynchos Wagler, 1827, and the carrion crow Corvus corone L., 1758, are two closely related species with similar ecological requirements that occupy wide distribution ranges in the Palearctic. We studied patterns of their genetic variation by using sequences of the mitochondrial cytochrome b gene. Corvus macrorhynchos demonstrates a low level of variation and differentiation throughout its range, except for a highly diverged population of Cheju Island (Korea). The haplotype network shows two haplogroups. The island group comprises populations of Sakhalin, Hokkaido, Honshu, and Kyushu, while the haplotypes of Taiwan and Ryukyu Islands proved to be closer to the mainland group, which also includes populations from the Primorye, Khabarovsk, Amur, and Magadan regions in the Russian Far East. This pattern allowed us to develop a phylogeographic hypothesis regarding the two modes of settling of the island populations. Concerning C. corone, the presence of two distinct haplogroups was confirmed within the range of C. c. orientalis. Both haplogroups are found within the same populations in Kamchatka and North Sakhalin, which implies secondary contacts there. Populations of C. corone are found to be rather stable in the western parts of its range, while in the Far East populations experienced recent growth, as was observed for C. macrorhynchos in general. The two species appear to have passed through different evolutionary scenarios.

  4. Comparative study of understorey birds diversity inhabiting lowland rainforest virgin jungle reserve and regenerated forest.

    PubMed

    Nor Hashim, Ezyan; Ramli, Rosli

    2013-01-01

    A comparative study of understorey birds inhabiting different habitats, that is, virgin jungle reserve (VJR) and regenerated forest (RF), was conducted in Ulu Gombak Forest Reserve and Selangor and Triang Forest Reserve, Negeri Sembilan, Peninsular Malaysia. The objective of this study was to assess the diversity of understorey birds in both habitats and the effects of forest regeneration on the understorey bird community. The mist-netting method was used to capture understorey birds inhabiting both habitats in both locations. Species composition and feeding guild indicated that understorey bird populations were similar in the two habitats. However, the number of secondary forest species such as Little spiderhunter (Arachnothera longirostra) in VJR is increasing due to its proximity to RF. This study discovered that RFs in both study areas are not yet fully recovered. However, based on the range of species discovered, the RFs have conservation value and should be maintained because they harbour important forest species such as babblers and flycatchers. The assessment of the community structure of understorey birds in VJR and RF is important for forest management and conservation, especially where both habitats are intact.

  5. In the jungle of time: the concept of identity as a way out.

    PubMed

    Zhou, Bin; Pöppel, Ernst; Bao, Yan

    2014-01-01

    WHAT COULD BE A UNIFYING PRINCIPLE FOR THE MANIFOLD OF TEMPORAL EXPERIENCES: the simultaneity or temporal order of events, the subjective present, the duration of experiences, or the impression of a continuity of time? Furthermore, we time travel to the past visiting in imagination previous experiences in episodic memory, and we also time travel to the future anticipating actions or plans. For such time traveling we divide time into three domains: past, present, and future. What could be an escape out of this "jungle of time" characterized by many different perceptual and conceptual phenomena? The key concept we want to propose is "identity" which is derived from homeostasis as a fundamental biological principle. Within this conceptual frame two modes of identity are distinguished: individual or self-identity required because of homeostatic demands, and object-related identity necessary for the reliability and efficiency of neuro-cognitive processing. With this concept of self- and object-identity, the different temporal experiences can be conceptualized within a common frame. Thus, we propose a fundamental biological principle to conceptually unify temporal phenomena on the psychological level.

  6. Hookworm infections in Singaporean soldiers after jungle training in Brunei Darussalam.

    PubMed

    Lee, Vernon J; Ong, Alan; Lee, Nan Guang; Lee, Wei Ting; Fong, Kenneth L; Lim, Poh Lian

    2007-12-01

    In June 2006, 118 Singaporean soldiers visited Brunei for jungle training for 10 days. Subsequently, two soldiers had severe diarrhoea and were diagnosed with severe hookworm infection. An epidemiological investigation and case-control study was conducted among the 118 soldiers. A survey was administered to determine the exposures predisposing to infection. Laboratory tests included a full blood count and three separate faecal screens via microscopy and culture. All servicemen were treated with one dose of mebendazole, and follow-up screening was performed 3 months later. Of 113 soldiers completing the questionnaire, 43 soldiers (38%) reported gastrointestinal symptoms post deployment, with 33 (29%) complaining of diarrhoea and 29 (26%) of abdominal pain. Eight had an itch or rash, but none were suggestive of cutaneous larva migrans. Of 103 soldiers completing both the questionnaire and with all the laboratory tests, 42 soldiers (41%) had eosinophilia (>0.6x10(9)/l) and 18 (17%) had hookworm infection on microscopy. More than 89% recalled substantial exposure to soil or groundwater, but no exposure was significantly associated with eosinophilia or infection. After adjusting for possible exposures, not wearing footwear during rest periods had a significantly higher odds ratio (2.86) for acquiring hookworm infection or eosinophilia. Helminth infections are common in visitors to rural Asia. As preventing exposure is often difficult, empirical treatment with anthelminthics should be considered in travellers to high risk areas.

  7. Functional compartmentalization of the human superficial masseter muscle.

    PubMed

    Guzmán-Venegas, Rodrigo A; Biotti Picand, Jorge L; de la Rosa, Francisco J Berral

    2015-01-01

    Some muscles have demonstrated a differential recruitment of their motor units in relation to their location and the nature of the motor task performed; this involves functional compartmentalization. There is little evidence that demonstrates the presence of a compartmentalization of the superficial masseter muscle during biting. The aim of this study was to describe the topographic distribution of the activity of the superficial masseter (SM) muscle's motor units using high-density surface electromyography (EMGs) at different bite force levels. Twenty healthy natural dentate participants (men: 4; women: 16; age 20±2 years; mass: 60±12 kg, height: 163±7 cm) were selected from 316 volunteers and included in this study. Using a gnathodynamometer, bites from 20 to 100% maximum voluntary bite force (MVBF) were randomly requested. Using a two-dimensional grid (four columns, six electrodes) located on the dominant SM, EMGs in the anterior, middle-anterior, middle-posterior and posterior portions were simultaneously recorded. In bite ranges from 20 to 60% MVBF, the EMG activity was higher in the anterior than in the posterior portion (p-value = 0.001).The center of mass of the EMG activity was displaced towards the posterior part when bite force increased (p-value = 0.001). The topographic distribution of EMGs was more homogeneous at high levels of MVBF (p-value = 0.001). The results of this study show that the superficial masseter is organized into three functional compartments: an anterior, a middle and a posterior compartment. However, this compartmentalization is only seen at low levels of bite force (20-60% MVBF). PMID:25692977

  8. Functional Compartmentalization of the Human Superficial Masseter Muscle

    PubMed Central

    Guzmán-Venegas, Rodrigo A.; Biotti Picand, Jorge L.; de la Rosa, Francisco J. Berral

    2015-01-01

    Some muscles have demonstrated a differential recruitment of their motor units in relation to their location and the nature of the motor task performed; this involves functional compartmentalization. There is little evidence that demonstrates the presence of a compartmentalization of the superficial masseter muscle during biting. The aim of this study was to describe the topographic distribution of the activity of the superficial masseter (SM) muscle’s motor units using high-density surface electromyography (EMGs) at different bite force levels. Twenty healthy natural dentate participants (men: 4; women: 16; age 20±2 years; mass: 60±12 kg, height: 163±7 cm) were selected from 316 volunteers and included in this study. Using a gnathodynamometer, bites from 20 to 100% maximum voluntary bite force (MVBF) were randomly requested. Using a two-dimensional grid (four columns, six electrodes) located on the dominant SM, EMGs in the anterior, middle-anterior, middle-posterior and posterior portions were simultaneously recorded. In bite ranges from 20 to 60% MVBF, the EMG activity was higher in the anterior than in the posterior portion (p-value = 0.001).The center of mass of the EMG activity was displaced towards the posterior part when bite force increased (p-value = 0.001). The topographic distribution of EMGs was more homogeneous at high levels of MVBF (p-value = 0.001). The results of this study show that the superficial masseter is organized into three functional compartments: an anterior, a middle and a posterior compartment. However, this compartmentalization is only seen at low levels of bite force (20–60% MVBF). PMID:25692977

  9. Functional compartmentalization of the human superficial masseter muscle.

    PubMed

    Guzmán-Venegas, Rodrigo A; Biotti Picand, Jorge L; de la Rosa, Francisco J Berral

    2015-01-01

    Some muscles have demonstrated a differential recruitment of their motor units in relation to their location and the nature of the motor task performed; this involves functional compartmentalization. There is little evidence that demonstrates the presence of a compartmentalization of the superficial masseter muscle during biting. The aim of this study was to describe the topographic distribution of the activity of the superficial masseter (SM) muscle's motor units using high-density surface electromyography (EMGs) at different bite force levels. Twenty healthy natural dentate participants (men: 4; women: 16; age 20±2 years; mass: 60±12 kg, height: 163±7 cm) were selected from 316 volunteers and included in this study. Using a gnathodynamometer, bites from 20 to 100% maximum voluntary bite force (MVBF) were randomly requested. Using a two-dimensional grid (four columns, six electrodes) located on the dominant SM, EMGs in the anterior, middle-anterior, middle-posterior and posterior portions were simultaneously recorded. In bite ranges from 20 to 60% MVBF, the EMG activity was higher in the anterior than in the posterior portion (p-value = 0.001).The center of mass of the EMG activity was displaced towards the posterior part when bite force increased (p-value = 0.001). The topographic distribution of EMGs was more homogeneous at high levels of MVBF (p-value = 0.001). The results of this study show that the superficial masseter is organized into three functional compartments: an anterior, a middle and a posterior compartment. However, this compartmentalization is only seen at low levels of bite force (20-60% MVBF).

  10. Compartmental Innervation of the Superior Oblique Muscle in Mammals

    PubMed Central

    Le, Alan; Poukens, Vadims; Ying, Howard; Rootman, Daniel; Goldberg, Robert A.; Demer, Joseph L.

    2015-01-01

    Purpose Intramuscular innervation of mammalian horizontal rectus extraocular muscles (EOMs) is compartmental. We sought evidence of similar compartmental innervation of the superior oblique (SO) muscle. Methods Three fresh bovine orbits and one human orbit were dissected to trace continuity of SO muscle and tendon fibers to the scleral insertions. Whole orbits were also obtained from four humans (two adults, a 17-month-old child, and a 33-week stillborn fetus), two rhesus monkeys, one rabbit, and one cow. Orbits were formalin fixed, embedded whole in paraffin, serially sectioned in the coronal plane at 10-μm thickness, and stained with Masson trichrome. Extraocular muscle fibers and branches of the trochlear nerve (CN4) were traced in serial sections and reconstructed in three dimensions. Results In the human, the lateral SO belly is in continuity with tendon fibers inserting more posteriorly on the sclera for infraducting mechanical advantage, while the medial belly is continuous with anteriorly inserting fibers having mechanical advantage for incycloduction. Fibers in the monkey superior SO insert more posteriorly on the sclera to favor infraduction, while the inferior portion inserts more anteriorly to favor incycloduction. In all species, CN4 bifurcates prior to penetrating the SO belly. Each branch innervates a nonoverlapping compartment of EOM fibers, consisting of medial and lateral compartments in humans and monkeys, and superior and inferior compartments in cows and rabbits. Conclusions The SO muscle of humans and other mammals is compartmentally innervated in a manner that could permit separate CN4 branches to selectively influence vertical versus torsional action. PMID:26426404

  11. Analytical properties of a three-compartmental dynamical demographic model

    NASA Astrophysics Data System (ADS)

    Postnikov, E. B.

    2015-07-01

    The three-compartmental demographic model by Korotaeyv-Malkov-Khaltourina, connecting population size, economic surplus, and education level, is considered from the point of view of dynamical systems theory. It is shown that there exist two integrals of motion, which enables the system to be reduced to one nonlinear ordinary differential equation. The study of its structure provides analytical criteria for the dominance ranges of the dynamics of Malthus and Kremer. Additionally, the particular ranges of parameters enable the derived general ordinary differential equations to be reduced to the models of Gompertz and Thoularis-Wallace.

  12. Rab Proteins and the Compartmentalization of the Endosomal System

    PubMed Central

    Wandinger-Ness, Angela; Zerial, Marino

    2014-01-01

    Of the approximately 70 human Rab GTPases, nearly three-quarters are involved in endocytic trafficking. Significant plasticity in endosomal membrane transport pathways is closely coupled to receptor signaling and Rab GTPase-regulated scaffolds. Here we review current literature pertaining to endocytic Rab GTPase localizations, functions, and coordination with regulatory proteins and effectors. The roles of Rab GTPases in (1) compartmentalization of the endocytic pathway into early, recycling, late, and lysosomal routes; (2) coordination of individual transport steps from vesicle budding to fusion; (3) effector interactomes; and (4) integration of GTPase and signaling cascades are discussed. PMID:25341920

  13. Ecology Driving Genetic Variation: A Comparative Phylogeography of Jungle Cat (Felis chaus) and Leopard Cat (Prionailurus bengalensis) in India

    PubMed Central

    Mukherjee, Shomita; Krishnan, Anand; Tamma, Krishnapriya; Home, Chandrima; R, Navya; Joseph, Sonia; Das, Arundhati; Ramakrishnan, Uma

    2010-01-01

    Background Comparative phylogeography links historical population processes to current/ecological processes through congruent/incongruent patterns of genetic variation among species/lineages. Despite high biodiversity, India lacks a phylogeographic paradigm due to limited comparative studies. We compared the phylogenetic patterns of Indian populations of jungle cat (Felis chaus) and leopard cat (Prionailurus bengalensis). Given similarities in their distribution within India, evolutionary histories, body size and habits, congruent patterns of genetic variation were expected. Methodology/Principal Findings We collected scats from various biogeographic zones in India and analyzed mtDNA from 55 jungle cats (460 bp NADH5, 141 bp cytochrome b) and 40 leopard cats (362 bp NADH5, 202 bp cytochrome b). Jungle cats revealed high genetic variation, relatively low population structure and demographic expansion around the mid-Pleistocene. In contrast, leopard cats revealed lower genetic variation and high population structure with a FST of 0.86 between North and South Indian populations. Niche-model analyses using two approaches (BIOCLIM and MaxEnt) support absence of leopard cats from Central India, indicating a climate associated barrier. We hypothesize that high summer temperatures limit leopard cat distribution and that a rise in temperature in the peninsular region of India during the LGM caused the split in leopard cat population in India. Conclusions/Significance Our results indicate that ecological variables describing a species range can predict genetic patterns. Our study has also resolved the confusion over the distribution of the leopard cat in India. The reciprocally monophyletic island population in the South mandates conservation attention. PMID:21060831

  14. Knowledge and power: the asymmetry of interests of Colombian and Rockefeller doctors in the construction of the concept of "jungle yellow fever," 1907-19381.

    PubMed

    Quevedo, Emilio; Manosalva, Carolina; Tafur, Monica; Bedoya, Joanna; Matiz, Giovanna; Morales, Elquin

    2008-01-01

    This study examines the asymmetries among the different interests of officials and medical doctors who worked for the Rockefeller Foundation and their Colombian counterparts in the development and consolidation of the concept of "jungle yellow fever," as distinguished from the known urban form of yellow fever. We explore the research responses to a variety of disease outbreaks in Colombia in the context of the Rockefeller campaigns against yellow fever, from the time of Roberto Franco's initial description of "yellow fever of the forests" in 1907 until the consolidation of the concept of "jungle yellow fever" by Fred Soper in 1938.

  15. Reproductive tract infections in rural women from the highlands, jungle, and coastal regions of Peru.

    PubMed Central

    García, Patricia J.; Chavez, Susana; Feringa, Barbara; Chiappe, Marina; Li, Weili; Jansen, Kathrin U.; Cárcamo, César; Holmes, King K.

    2004-01-01

    OBJECTIVE: To define the prevalences and manifestations of reproductive tract infections (RTIs) in rural Peruvian women. METHODS: During 1997-98, we visited 18 rural districts in coastal, highlands, and jungle regions of Peru. We administered standardized questionnaires and pelvic examinations to members of women's community-based organizations; and collected vaginal fluid for pH, amine odour, Gram stain, microscopy, and culture for Trichomonas vaginalis; cervical specimens for Chlamydia trachomatis, Neisseria gonorrhoeae; human papilloma virus (HPV) by polymerase chain reaction (PCR) assays, and blood for syphilis serology. FINDINGS: The 754 participants averaged 36.9 years of age and 1.7 sex partners ever; 77% reported symptoms indicative of RTIs; 51% and 26% reported their symptoms spontaneously or only with specific questioning, respectively. Symptoms reported spontaneously included abnormal vaginal discharge (29.3% and 22.9%, respectively). One or more RTIs, found in 70.4% of participants, included bacterial vaginosis (43.7%), trichomoniasis (16.5%), vulvovaginal candidiasis (4.5%), chlamydial infection (6.8%), gonorrhoea (1.2%), syphilis seropositivity (1.7%), cervical HPV infection (4.9%), and genital warts or ulcers (2.8%). Of 715 adequate Pap smears, 7 revealed cancer, 4 high-grade squamous intra-epithelial lesions (SIL) and 15 low-grade SIL. Clinical algorithms had very low sensitivity and predictive values for cervical infection, but over half the women with symptoms of malodorous vaginal discharge, signs of abnormal vaginal discharge, or both, had bacterial vaginosis or trichomoniasis. CONCLUSION: Overall, 77% of women had symptoms indicative of RTIs, and 70% had objective evidence of one or more RTIs. Women with selected symptoms and signs of vaginal infection could benefit from standard metronidazole therapy. PMID:15508193

  16. Organic tissues, graphite, and hydrocarbons in host rocks of the Rum Jungle Uranium Field, northern Australia

    USGS Publications Warehouse

    Foster, C.B.; Robbins, E.I.; Bone, Y.

    1990-01-01

    The Rum Jungle Uranium field consists of at least six early Proterozoic deposits that have been mined either for uranium and/or the associated base and precious metals. Organic matter in the host rocks of the Whites Formation and Coomalie Dolomite is now predominantly graphite, consistent with the metamorphic history of these rocks. For nine samples, the mean total organic carbon content is high (3.9 wt%) and ranged from 0.33 to 10.44 wt%. Palynological extracts from the host rocks include black, filamentous, stellate (Eoastrion-like), and spherical morphotypes, which are typical of early Proterozoic microbiota. The colour, abundance, and shapes of these morphotypes reflect the thermal history, organic richness, and probable lacustrine biofacies of the host rocks. Routine analysis of rock thin sections and of palynological residues shows that mineral grains in some of the host rocks are coated with graphitized organic matter. The grain coating is presumed to result from ultimate thermal degradation of a petroleum phase that existed prior to metamorphism. Hydrocarbons are, however, still present in fluid inclusions within carbonates of the Coomalie Dolomite and lower Whites Formation. The fluid inclusions fluoresce dull orange in blue-light excitation and their hydrocarbon content is confirmed by gas chromatography of whole-rock extracts. Preliminary analysis of the oil suggests that it is migrated, and because it has escaped graphitization through metamorphism it is probably not of early Proterozoic age. The presence of live oil is consistent with fluid inclusion data that suggest subsequent, low-temperature brine migration through the rocks. The present observations support earlier suggestions that organic matter in the host formations trapped uranium to form protore. Subsequent fluid migrations probably brought additional uranium and other metals to these formations, and the organic matter provided a reducing environment for entrapment. ?? 1990.

  17. Temporal structure of red jungle fowl crow sequences: single-case analysis.

    PubMed

    Koene, P

    1996-11-01

    Vocalisations can be indicators of the physical state or condition of an animal, for instance the crow of a rooster. There are no published data on the temporal structure of crow sequences. In this paper 536 crows in 22 sequences of one red jungle fowl rooster (rooster 1) were recorded and analysed. Calls were very characteristic and there was little variation between the calls. Rooster 1 crowed with a mean latency of 287 s after onset of a light in the early morning. The average crow sequence consisted of 29 calls which lasted for 1416 ms on average. A gradual increase in pre-call interval was characteristic of each sequence. The variation in note durations is systematic and especially the last note correlated highly with the total call duration. Both the pre-call interval and the duration of the 4th note (doooo) may be parameters of fatigue and thus of physical condition. The number of crows in a sequence was positively related to air pressure outdoors. An experiment is done in which the physical condition of a rooster (rooster 2) is manipulated by food deprivation. The results are analysed with single case randomisation tests. The number of crows in a sequence is significantly reduced after food deprivation, while the pre-call intervals are significantly increased. Prediction of the number of crows in the sequence can be done on base of the pre-call interval of the second call: both rooster 1 and 2 showed long pre-call intervals in short call sequences. Food deprivation and the possible loss of condition have a significant effect on the temporal structure of crow sequences and cause a decrease in the number of crows in a call sequence. PMID:24896081

  18. Directed evolution of polymerase function by compartmentalized self-replication

    PubMed Central

    Ghadessy, Farid J.; Ong, Jennifer L.; Holliger, Philipp

    2001-01-01

    We describe compartmentalized self-replication (CSR), a strategy for the directed evolution of enzymes, especially polymerases. CSR is based on a simple feedback loop consisting of a polymerase that replicates only its own encoding gene. Compartmentalization serves to isolate individual self-replication reactions from each other. In such a system, adaptive gains directly (and proportionally) translate into genetic amplification of the encoding gene. CSR has applications in the evolution of polymerases with novel and useful properties. By using three cycles of CSR, we obtained variants of Taq DNA polymerase with 11-fold higher thermostability than the wild-type enzyme or with a >130-fold increased resistance to the potent inhibitor heparin. Insertion of an extra stage into the CSR cycle before the polymerase reaction allows its application to enzymes other than polymerases. We show that nucleoside diphosphate kinase and Taq polymerase can form such a cooperative CSR cycle based on reciprocal catalysis, whereby nucleoside diphosphate kinase produces the substrates required for the replication of its own gene. We also find that in CSR the polymerase genes themselves evolve toward more efficient replication. Thus, polymerase genes and their encoded polypeptides cooperate to maximize postselection copy number. CSR should prove useful for the directed evolution of enzymes, particularly DNA or RNA polymerases, as well as for the design and study of in vitro self-replicating systems mimicking prebiotic evolution and viral replication. PMID:11274352

  19. Super-resolution Microscopy Reveals Compartmentalization of Peroxisomal Membrane Proteins*

    PubMed Central

    Galiani, Silvia; Waithe, Dominic; Reglinski, Katharina; Cruz-Zaragoza, Luis Daniel; Garcia, Esther; Clausen, Mathias P.; Schliebs, Wolfgang; Erdmann, Ralf; Eggeling, Christian

    2016-01-01

    Membrane-associated events during peroxisomal protein import processes play an essential role in peroxisome functionality. Many details of these processes are not known due to missing spatial resolution of technologies capable of investigating peroxisomes directly in the cell. Here, we present the use of super-resolution optical stimulated emission depletion microscopy to investigate with sub-60-nm resolution the heterogeneous spatial organization of the peroxisomal proteins PEX5, PEX14, and PEX11 around actively importing peroxisomes, showing distinct differences between these peroxins. Moreover, imported protein sterol carrier protein 2 (SCP2) occupies only a subregion of larger peroxisomes, highlighting the heterogeneous distribution of proteins even within the peroxisome. Finally, our data reveal subpopulations of peroxisomes showing only weak colocalization between PEX14 and PEX5 or PEX11 but at the same time a clear compartmentalized organization. This compartmentalization, which was less evident in cases of strong colocalization, indicates dynamic protein reorganization linked to changes occurring in the peroxisomes. Through the use of multicolor stimulated emission depletion microscopy, we have been able to characterize peroxisomes and their constituents to a yet unseen level of detail while maintaining a highly statistical approach, paving the way for equally complex biological studies in the future. PMID:27311714

  20. Building America Case Study: Field Testing of Compartmentalization Methods for Multifamily Construction (Fact Sheet)

    SciTech Connect

    Not Available

    2015-01-01

    The 2012 IECC has an airtightness requirement of 3 air changes per hour at 50 Pascals test pressure for both single family and multifamily construction in Climate Zones 3-8. Other programs (LEED, ASHRAE 189, ASHRAE 62.2) have similar or tighter compartmentalization requirements, thus driving the need for easier and more effective methods of compartmentalization in multifamily buildings.

  1. Physiological Consequences of Compartmentalized Acyl-CoA Metabolism*

    PubMed Central

    Cooper, Daniel E.; Young, Pamela A.; Klett, Eric L.; Coleman, Rosalind A.

    2015-01-01

    Meeting the complex physiological demands of mammalian life requires strict control of the metabolism of long-chain fatty acyl-CoAs because of the multiplicity of their cellular functions. Acyl-CoAs are substrates for energy production; stored within lipid droplets as triacylglycerol, cholesterol esters, and retinol esters; esterified to form membrane phospholipids; or used to activate transcriptional and signaling pathways. Indirect evidence suggests that acyl-CoAs do not wander freely within cells, but instead, are channeled into specific pathways. In this review, we will discuss the evidence for acyl-CoA compartmentalization, highlight the key modes of acyl-CoA regulation, and diagram potential mechanisms for controlling acyl-CoA partitioning. PMID:26124277

  2. Apartment Compartmentalization With an Aerosol-Based Sealing Process

    SciTech Connect

    Maxwell, S.; Berger, D.; Harrington, C.

    2015-03-01

    Air sealing of building enclosures is a difficult and time-consuming process. Current methods in new construction require laborers to physically locate small and sometimes large holes in multiple assemblies and then manually seal each of them. The innovation demonstrated under this research study was the automated air sealing and compartmentalization of buildings through the use of an aerosolized sealant, developed by the Western Cooling Efficiency Center at University of California Davis. CARB sought to demonstrate this new technology application in a multifamily building in Queens, NY. The effectiveness of the sealing process was evaluated by three methods: air leakage testing of overall apartment before and after sealing, point-source testing of individual leaks, and pressure measurements in the walls of the target apartment during sealing.

  3. Hydrological Compartmentalization: A Grand Challenge in the Critical Zone

    NASA Astrophysics Data System (ADS)

    McDonnell, J.; Evaristo, J. A.; Orlowski, N.; Jasechko, S.

    2015-12-01

    Current terrestrial biosphere models assume that plant transpiration, groundwater and streamflow are all sourced and mediated by the same well mixed soil reservoir. Recent stable water isotope data from Oregon and Mexico and now global meta-analysis and remote sensing measurements have all shown evidence of hydrological compartmentalization: a mobile compartment that forms groundwater and streamflow and a poorly mobile compartment that supplies plant transpiration. The way we now measure and model this poorly mobile water is a grand challenge for understanding subsurface mixing, water residence time, and its interaction and feedback to ecosystem processes. Here we review the latest results from this work and outline some of the future research challenges for understanding soil-plant-atmospheric interactions between the bedrock and the boundary layer.

  4. Compartmentalization of NO signaling cascade in skeletal muscles

    SciTech Connect

    Buchwalow, Igor B. . E-mail: buchwalo@uni-muenster.de; Minin, Evgeny A.; Samoilova, Vera E.; Boecker, Werner; Wellner, Maren; Schmitz, Wilhelm; Neumann, Joachim

    2005-05-06

    Skeletal muscle functions regulated by NO are now firmly established. However, the literature on the compartmentalization of NO signaling in myocytes is highly controversial. To address this issue, we examined localization of enzymes engaged in L-arginine-NO-cGMP signaling in the rat quadriceps muscle. Employing immunocytochemical labeling complemented with tyramide signal amplification and electron microscopy, we found NO synthase expressed not only in the sarcolemma, but also along contractile fibers, in the sarcoplasmic reticulum and mitochondria. The expression pattern of NO synthase in myocytes showed striking parallels with the enzymes engaged in L-arginine-NO-cGMP signaling (arginase, phosphodiesterase, and soluble guanylyl cyclase). Our findings are indicative of an autocrine fashion of NO signaling in skeletal muscles at both cellular and subcellular levels, and challenge the notion that the NO generation is restricted to the sarcolemma.

  5. Compartmentation of enzymes interconverting aclacinomycins in Streptomyces species AM 33352.

    PubMed

    Gräfe, U; Dornberger, K; Fleck, W F; Freysoldt, C

    1988-01-01

    The enzymatic interconversion of the aclacinomycins A (I), Y (II), and B (III) by Streptomyces spec. AM 33352/S 182 producing these aklavinone glycosides was investigated. The enzymes converting I to II and III, as well as vice versa, are located within different compartments separated by the cytoplasmic membrane. Aclacinomycin A (I) is biotransformed to II and III by the cell-free mycelium extract while the entire mycelium carries out the same type of conversion towards the opposite direction. Changes of enzyme activity are correlated to alterations in the ratio of aklavinone glycosides throughout the fermentation. A hypothesis is developed concerning the role of compartmentized oxidoreductase(s) in the passive flux of I from inside the cells to outside.

  6. The human NAD metabolome: Functions, metabolism and compartmentalization

    PubMed Central

    Nikiforov, Andrey; Kulikova, Veronika; Ziegler, Mathias

    2015-01-01

    Abstract The metabolism of NAD has emerged as a key regulator of cellular and organismal homeostasis. Being a major component of both bioenergetic and signaling pathways, the molecule is ideally suited to regulate metabolism and major cellular events. In humans, NAD is synthesized from vitamin B3 precursors, most prominently from nicotinamide, which is the degradation product of all NAD-dependent signaling reactions. The scope of NAD-mediated regulatory processes is wide including enzyme regulation, control of gene expression and health span, DNA repair, cell cycle regulation and calcium signaling. In these processes, nicotinamide is cleaved from NAD+ and the remaining ADP-ribosyl moiety used to modify proteins (deacetylation by sirtuins or ADP-ribosylation) or to generate calcium-mobilizing agents such as cyclic ADP-ribose. This review will also emphasize the role of the intermediates in the NAD metabolome, their intra- and extra-cellular conversions and potential contributions to subcellular compartmentalization of NAD pools. PMID:25837229

  7. Molecular Mechanisms of Compartmentalization and Biomineralization in Magnetotactic Bacteria

    PubMed Central

    Komeili, Arash

    2011-01-01

    Magnetotactic bacteria are remarkable organisms with the ability to exploit the earth’s magnetic field for navigational purposes. To do this, they build specialized compartments called magnetosomes that consist of a lipid membrane and a crystalline magnetic mineral. These organisms have the potential to serve as models for the study of compartmentalization as well as biomineralization in bacteria. Additionally, they offer the opportunity to design applications that take advantage of the particular properties of magnetosomes. In recent years, a sustained effort to identify the molecular basis of this process has resulted in a clearer understanding of the magnetosome formation and biomineralization. Here, I present an overview of magnetotactic bacteria and explore the possible molecular mechanisms of membrane remodeling, protein sorting, cytoskeletal organization, iron transport and biomineralization that lead to the formation of a functional magnetosome organelle. PMID:22092030

  8. Hydrological Compartmentalization: A Grand Challenge in the Critical Zone

    NASA Astrophysics Data System (ADS)

    McDonnell, J.; Evaristo, J. A.; Orlowski, N.; Jasechko, S.

    2014-12-01

    Current terrestrial biosphere models assume that plant transpiration, groundwater and streamflow are all sourced and mediated by the same well mixed soil reservoir. Recent stable water isotope data from Oregon and Mexico and now global meta-analysis and remote sensing measurements have all shown evidence of hydrological compartmentalization: a mobile compartment that forms groundwater and streamflow and a poorly mobile compartment that supplies plant transpiration. The way we now measure and model this poorly mobile water is a grand challenge for understanding subsurface mixing, water residence time, and its interaction and feedback to ecosystem processes. Here we review the latest results from this work and outline some of the future research challenges for understanding soil-plant-atmospheric interactions between the bedrock and the boundary layer.

  9. Sharpness of Spike Initiation in Neurons Explained by Compartmentalization

    PubMed Central

    Brette, Romain

    2013-01-01

    In cortical neurons, spikes are initiated in the axon initial segment. Seen at the soma, they appear surprisingly sharp. A standard explanation is that the current coming from the axon becomes sharp as the spike is actively backpropagated to the soma. However, sharp initiation of spikes is also seen in the input–output properties of neurons, and not only in the somatic shape of spikes; for example, cortical neurons can transmit high frequency signals. An alternative hypothesis is that Na channels cooperate, but it is not currently supported by direct experimental evidence. I propose a simple explanation based on the compartmentalization of spike initiation. When Na channels are placed in the axon, the soma acts as a current sink for the Na current. I show that there is a critical distance to the soma above which an instability occurs, so that Na channels open abruptly rather than gradually as a function of somatic voltage. PMID:24339755

  10. Approximating the stabilization of cellular metabolism by compartmentalization.

    PubMed

    Fürtauer, Lisa; Nägele, Thomas

    2016-06-01

    Biochemical regulation in compartmentalized metabolic networks is highly complex and non-intuitive. This is particularly true for cells of higher plants showing one of the most compartmentalized cellular structures across all kingdoms of life. The interpretation and testable hypothesis generation from experimental data on such complex systems is a challenging step in biological research and biotechnological applications. While it is known that subcellular compartments provide defined reaction spaces within a cell allowing for the tight coordination of complex biochemical reaction sequences, its role in the coordination of metabolic signals during metabolic reprogramming due to environmental fluctuations is less clear. In the present study, we numerically analysed the effects of environmental fluctuations in a subcellular metabolic network with regard to the stability of an experimentally observed steady state in the genetic model plant Arabidopsis thaliana. Applying a method for kinetic parameter normalization, several millions of probable enzyme kinetic parameter constellations were simulated and evaluated with regard to the stability information of the metabolic homeostasis. Information about the stability of the metabolic steady state was derived from real parts of eigenvalues of Jacobian matrices. Our results provide evidence for a differential stabilizing contribution of different subcellular compartments. We could identify stabilizing and destabilizing network components which we could classify according to their subcellular localization. The findings prove that a highly dynamic interplay between intracellular compartments is preliminary for an efficient stabilization of a metabolic homeostasis after environmental perturbation. Further, our results provide evidence that feedback-inhibition originating from the cytosol and plastid seem to stabilize the sucrose homeostasis more efficiently than vacuolar control. In summary, our results indicate stabilizing and

  11. Linear systems, compartmental modeling, and estimability issues in IAQ studies

    SciTech Connect

    Evans, W.C.

    1996-12-31

    Many IAQ models are expressed as coupled systems of linear, ordinary differential equations. In this paper, the linear-systems or state-variable format for these systems will be reviewed, and some useful information will be presented which can be obtained from this formulation without explicitly solving the differential equation system. Much information concerning linear systems analysis is available in the literature of various disciplines, particularly biomathematics, wherein there is a specialization called compartmental modeling. It is important to recognize that there exists a great deal of directly usable mathematical information which can immediately be applied to IAQ modeling problems. In compartmental modeling, an issue called identifiability has long been recognized as a potential problem with experiments that are intended to extract information about a linear system`s parameters from observations of that system`s response to a forcing function. It can happen that the system`s parameters cannot be uniquely estimated from an experiment, no matter how good (noise-free) the measurements are. With a linear-systems formulation of the experimental configuration, this condition can be detected before the experiment is conducted. A related issue is termed redundancy, which refers to the inability to obtain unique parameter estimates from the data, even if the experiment is identifiable. This problem occurs for sums-of-exponentials models, fitted via nonlinear estimation to the observations. Taken together, identifiability and redundancy can be termed estimability. These difficulties can affect chamber testing in particular, since this is the context where they are attempting to estimate system parameters from observations. This paper will present an overview of these issues, with selected examples.

  12. Cadherins in cerebellar development: translation of embryonic patterning into mature functional compartmentalization.

    PubMed

    Redies, Christoph; Neudert, Franziska; Lin, Juntang

    2011-09-01

    Cadherins are cell adhesion molecules with multiple morphogenic functions in brain development, for example, in neuroblast migration and aggregation, axon navigation, neural circuit formation, and synaptogenesis. More than 100 members of the cadherin superfamily are expressed in the developing and mature brain. Most of the cadherins investigated, in particular classic cadherins and δ-protocadherins, are expressed in the cerebellum. For several cadherin subtypes, expression begins at early embryonic stages and persists until mature stages of cerebellar development. At intermediate stages, distinct Purkinje cell clusters exhibit unique rostrocaudal and mediolateral expression profiles for each cadherin. In the chicken, mouse, and other species, the Purkinje cell clusters are separated by intervening raphes of migrating granule cells. This pattern of Purkinje cell clusters/raphes is, at least in part, continuous with the parasagittal striping pattern that is apparent in the mature cerebellar cortex, for example, for zebrin II/aldolase C. Moreover, subregions of the deep cerebellar nuclei, vestibular nuclei and the olivary complex also express cadherins differentially. Neuroanatomical evidence suggests that the nuclear subregions and cortical domains that express the same cadherin subtype are connected to each other, to form neural subcircuits of the cerebellar system. Cadherins thus provide a molecular code that specifies not only embryonic structures but also functional cerebellar compartmentalization. By following the implementation of this code, it can be revealed how mature functional architecture emerges from embryonic patterning during cerebellar development. Dysfunction of some cadherins is associated with psychiatric diseases and developmental impairments and may also affect cerebellar function.

  13. Compartmentation of sucrose during radial transfer in mature sorghum culm

    PubMed Central

    Tarpley, Lee; Vietor, Donald M

    2007-01-01

    Background The sucrose that accumulates in the culm of sorghum (Sorghum bicolor (L.) Moench) and other large tropical andropogonoid grasses can be of commercial value, and can buffer assimilate supply during development. Previous study conducted with intact plants showed that sucrose can be radially transferred to the intracellular compartment of mature ripening sorghum internode without being hydrolysed. In this study, culm-infused radiolabelled sucrose was traced between cellular compartments and among related metabolites to determine if the compartmental path of sucrose during radial transfer in culm tissue was symplasmic or included an apoplasmic step. This transfer path was evaluated for elongating and ripening culm tissue of intact plants of two semidwarf grain sorghums. The metabolic path in elongating internode tissue was also evaluated. Results On the day after culm infusion of the tracer sucrose, the specific radioactivity of sucrose recovered from the intracellular compartment of growing axillary-branch tissue was greater (nearly twice) than that in the free space, indicating that sucrose was preferentially transferred through symplasmic routes. In contrast, the sucrose specific radioactivity in the intracellular compartment of the mature (ripening) culm tissue was probably less (about 3/4's) than that in free space indicating that sucrose was preferentially transferred through routes that included an apoplasmic step. In growing internodes of the axillary branch of sorghum, the tritium label initially provided in the fructose moiety of sucrose molecules was largely (81%) recovered in the fructose moiety, indicating that a large portion of sucrose molecules is not hydrolysed and resynthesized during radial transfer. Conclusion During radial transfer of sucrose in ripening internodes of intact sorghum plants, much of the sucrose is transferred intact (without hydrolysis and resynthesis) and primarily through a path that includes an apoplasmic step. In

  14. The geological setting of tourmalinite at Rum Jungle, N.T., Australia — genetic and economic implications

    NASA Astrophysics Data System (ADS)

    Bone, Yvonne

    1988-01-01

    Tourmalinite is a common rock type associated with Proterozoic strata-bound mineral deposits. Although common, it is often difficult to recognise in the field, leading to misidentification. It occurs as a conformable banded quartz-tourmaline lithological unit comprising at least 15% and as much as 50% of the rock. At Rum Jungle, tourmalinite occurs within the oldest sediments (arenites and magnesites) as distinct lenses, as facies equivalents of quartz-magnetite units and mafic schists (tuffs?) and distal equivalents of polymetallic sulfides. Distinct layering, slump folding, rip-up clasts and the association with diagenetic pyrite suggest a sedimentary environment. Enechelon fracturing of the fine-grained, light green tourmaline crystals spectacularly supports pre-deformation formation. The crystals are optically and chemically zoned parallel to the c axis, with irregular growth lamellae width — which supports a pre-regional metamorphic origin. Analyses show the tourmaline to be the Mg-rich variety “dravite”. Most tourmalinites are interpreted as subaqueous marine deposits. It is more likely that they form in lacustrine, shallow water, evaporitic environments, particularly continental rifts. Suitable B-bearing fluids can be generated by hotspring activity and mobilized by CO2-rich fluids. Association with chemical sediments suggests tourmalinites also have a chemical sediment precursor. Ample evidence at Rum Jungle supports the notion of a continental rift environment, which was the site of deposition of fluvial arenites and alkaline, evaporitic lake sediments. Localised hot-spring activity contributed B-bearing fluids which precipitated chemical sediments according to the pertaining pH, temperature etc. Diagenetic alteration produced the tourmalinite now present. These tourmalinites are comparable to those of similar age elsewhere e.g. Sullivan, Broken Hill. They can be genetically modelled upon Recent borate concentrations, all of which occur in

  15. A development-based compartmentalization of the Drosophila central brain

    PubMed Central

    Pereanu, Wayne; Kumar, Abilasha; Jennett, Arnim; Reichert, Heinrich; Hartenstein, Volker

    2010-01-01

    The neuropile of the Drosophila brain is subdivided into anatomically discrete compartments. Compartments are rich in terminal neurite branching and synapses; they are the neuropile domains in which signal processing takes place. Compartment boundaries are defined by more or less dense layers of glial cells, as well as long neurite fascicles. These fascicles are formed during the larval period when the approximately 100 neuronal lineages that constitute the Drosophila central brain differentiate. Each lineage forms an axon tract with a characteristic trajectory in the neuropile; groups of spatially related tracts congregate into the brain fascicles that can be followed from the larva throughout metamorphosis into the adult stage. In this paper we provide a map of the adult brain compartments and the relevant fascicles defining compartmental boundaries. We have identified the neuronal lineages contributing to each fascicle, which allowed us to directly compare compartments of the larval and adult brain. Most adult compartments can be recognized already in the early larval brain where they form a “protomap” of the later adult compartments. Our analysis highlights the morphogenetic changes shaping the Drosophila brain; the data will be important for studies that link early acting genetic mechanisms to the adult neuronal structures and circuits controlled by these mechanisms. PMID:20533357

  16. Photoacoustic "nanobombs" fight against undesirable vesicular compartmentalization of anticancer drugs.

    PubMed

    Chen, Aiping; Xu, Chun; Li, Min; Zhang, Hailin; Wang, Diancheng; Xia, Mao; Meng, Gang; Kang, Bin; Chen, Hongyuan; Wei, Jiwu

    2015-01-01

    Undesirable intracellular vesicular compartmentalization of anticancer drugs in cancer cells is a common cause of chemoresistance. Strategies aimed at circumventing this problem may improve chemotherapeutic efficacy. We report a novel photophysical strategy for controlled-disruption of vesicular sequestration of the anticancer drug doxorubicin (DOX). Single-walled carbon nanotubes (SWCNTs), modified with folate, were trapped in acidic vesicles after entering lung cancer cells. Upon irradiation by near-infrared pulsed laser, these vesicles were massively broken by the resulting photoacoustic shockwave, and the vesicle-sequestered contents were released, leading to redistribution of DOX from cytoplasm to the target-containing nucleus. Redistribution resulted in 12-fold decrease of the EC50 of DOX in lung cancer cells, and enhanced antitumor efficacy of low-dose DOX in tumor-bearing mice. Side effects were not observed. These findings provide insights of using nanotechnology to improve cancer chemotherapy, i.e. not only for drug delivery, but also for overcoming intracellular drug-transport hurdles.

  17. Compartmentation of cellular tetrahydrofolate pools in rat liver

    SciTech Connect

    Barlowe, C.K.; Appling, D.R.

    1987-05-01

    Folate coenzymes are essential in shuttling one carbon units between a number of cellular processes. Serine, glycine, histidine and formate may serve as one-carbon sources by donation of their one-carbon unit to tetrahydrofolate (THF) which may then be utilized in the biosynthesis of nucleic acids and amino acids or oxidized to carbon dioxide (CO/sub 2/) via formyl-THF dehydrogenase. Nitrous Oxide (N/sub 2/O) has been observed to inactivate methionine synthase causing an increase in the cellular concentration of methyl-THF at the expense of other folate forms, specifically THF. They are interested in determining if THF dependent pathways that utilize serine, formate and histidine are equally effected by N/sub 2/O. Radiometric methods indicate that oxidation of the ..beta..-carbon of serine to CO/sub 2/ is uneffected by N/sub 2/O exposure, but oxidation of formate and the 2-ring carbon of histidine to CO/sub 2/ are reduced by about 50% and 95% of control levels, respectively. In contrast, the use of these one carbon sources for purine biosynthesis are all reduced roughly 50% upon exposure to N/sub 2/O. These data suggest an intracellular compartmentation of THF pools available to different sources of one-carbon units.

  18. Compartmentalized nitric oxide signaling in the resistance vasculature.

    PubMed

    Mutchler, Stephanie M; Straub, Adam C

    2015-09-15

    Nitric oxide (NO) was first described as a bioactive molecule through its ability to stimulate soluble guanylate cyclase, but the revelation that NO was the endothelium derived relaxation factor drove the field to its modern state. The wealth of research conducted over the past 30 years has provided us with a picture of how diverse NO signaling can be within the vascular wall, going beyond simple vasodilation to include such roles as signaling through protein S-nitrosation. This expanded view of NO's actions requires highly regulated and compartmentalized production. Importantly, resistance arteries house multiple proteins involved in the production and transduction of NO allowing for efficient movement of the molecule to regulate vascular tone and reactivity. In this review, we focus on the many mechanisms regulating NO production and signaling action in the vascular wall, with a focus on the control of endothelial nitric oxide synthase (eNOS), the enzyme responsible for synthesizing most of the NO within these confines. We also explore how cross talk between the endothelium and smooth muscle in the microcirculation can modulate NO signaling, illustrating that this one small molecule has the capability to produce a plethora of responses.

  19. An integrated compartmental model for prediction of indoor radon concentrations

    SciTech Connect

    Al-Ahmady, K.K.; Hintenlang, D.E.

    1995-12-31

    A carefully selected, heavily instrumented, and fully controlled experimental facility dedicated to research was used to investigate the interaction and effects of key parameters related to the indoor radon problem. Mechanistic and empirical models have been developed in which they return pressure differentials in response to indoor radon driving forces inputs. A semi-diurnal natural pumping model of radon-rich soil gas was based on an exponentially damped response of the sub-slab air volume pressure to changes in atmospheric pressure. A wind-induced pressure differentials model was based on the conservation of energy of the wind speed between the main stream and the structure shell corrected to the effect of wind fluctuation and direction. A temperature-induced pressure differential model was based on the linear approximation of the weakly exponentially-dependent pressures between two temperature zones under hydrostatic equilibrium. Mathematical frameworks were developed to incorporate driving force models into an integrated compartmental model allowed predictions of time-integrated and time-dependent indoor radon concentrations. The integrated predictions are in good agreement with the observed concentrations at the research site.

  20. Shape control and compartmentalization in active colloidal cells

    PubMed Central

    Spellings, Matthew; Engel, Michael; Klotsa, Daphne; Sabrina, Syeda; Drews, Aaron M.; Nguyen, Nguyen H. P.; Bishop, Kyle J. M.; Glotzer, Sharon C.

    2015-01-01

    Small autonomous machines like biological cells or soft robots can convert energy input into control of function and form. It is desired that this behavior emerges spontaneously and can be easily switched over time. For this purpose we introduce an active matter system that is loosely inspired by biology and which we term an active colloidal cell. The active colloidal cell consists of a boundary and a fluid interior, both of which are built from identical rotating spinners whose activity creates convective flows. Similarly to biological cell motility, which is driven by cytoskeletal components spread throughout the entire volume of the cell, active colloidal cells are characterized by highly distributed energy conversion. We demonstrate that we can control the shape of the active colloidal cell and drive compartmentalization by varying the details of the boundary (hard vs. flexible) and the character of the spinners (passive vs. active). We report buckling of the boundary controlled by the pattern of boundary activity, as well as formation of core–shell and inverted Janus phase-separated configurations within the active cell interior. As the cell size is increased, the inverted Janus configuration spontaneously breaks its mirror symmetry. The result is a bubble–crescent configuration, which alternates between two degenerate states over time and exhibits collective migration of the fluid along the boundary. Our results are obtained using microscopic, non–momentum-conserving Langevin dynamics simulations and verified via a phase-field continuum model coupled to a Navier–Stokes equation. PMID:26253763

  1. Adaptive and neuroadaptive control for nonnegative and compartmental dynamical systems

    NASA Astrophysics Data System (ADS)

    Volyanskyy, Kostyantyn Y.

    Neural networks have been extensively used for adaptive system identification as well as adaptive and neuroadaptive control of highly uncertain systems. The goal of adaptive and neuroadaptive control is to achieve system performance without excessive reliance on system models. To improve robustness and the speed of adaptation of adaptive and neuroadaptive controllers several controller architectures have been proposed in the literature. In this dissertation, we develop a new neuroadaptive control architecture for nonlinear uncertain dynamical systems. The proposed framework involves a novel controller architecture with additional terms in the update laws that are constructed using a moving window of the integrated system uncertainty. These terms can be used to identify the ideal system weights of the neural network as well as effectively suppress system uncertainty. Linear and nonlinear parameterizations of the system uncertainty are considered and state and output feedback neuroadaptive controllers are developed. Furthermore, we extend the developed framework to discrete-time dynamical systems. To illustrate the efficacy of the proposed approach we apply our results to an aircraft model with wing rock dynamics, a spacecraft model with unknown moment of inertia, and an unmanned combat aerial vehicle undergoing actuator failures, and compare our results with standard neuroadaptive control methods. Nonnegative systems are essential in capturing the behavior of a wide range of dynamical systems involving dynamic states whose values are nonnegative. A sub-class of nonnegative dynamical systems are compartmental systems. These systems are derived from mass and energy balance considerations and are comprised of homogeneous interconnected microscopic subsystems or compartments which exchange variable quantities of material via intercompartmental flow laws. In this dissertation, we develop direct adaptive and neuroadaptive control framework for stabilization, disturbance

  2. Photoacoustic "nanobombs" fight against undesirable vesicular compartmentalization of anticancer drugs.

    PubMed

    Chen, Aiping; Xu, Chun; Li, Min; Zhang, Hailin; Wang, Diancheng; Xia, Mao; Meng, Gang; Kang, Bin; Chen, Hongyuan; Wei, Jiwu

    2015-01-01

    Undesirable intracellular vesicular compartmentalization of anticancer drugs in cancer cells is a common cause of chemoresistance. Strategies aimed at circumventing this problem may improve chemotherapeutic efficacy. We report a novel photophysical strategy for controlled-disruption of vesicular sequestration of the anticancer drug doxorubicin (DOX). Single-walled carbon nanotubes (SWCNTs), modified with folate, were trapped in acidic vesicles after entering lung cancer cells. Upon irradiation by near-infrared pulsed laser, these vesicles were massively broken by the resulting photoacoustic shockwave, and the vesicle-sequestered contents were released, leading to redistribution of DOX from cytoplasm to the target-containing nucleus. Redistribution resulted in 12-fold decrease of the EC50 of DOX in lung cancer cells, and enhanced antitumor efficacy of low-dose DOX in tumor-bearing mice. Side effects were not observed. These findings provide insights of using nanotechnology to improve cancer chemotherapy, i.e. not only for drug delivery, but also for overcoming intracellular drug-transport hurdles. PMID:26483341

  3. MULTIMEDIA ENVIRONMENTAL DISTRIBUTION OF TOXICS (MEND-TOX): PART I, HYBRID COMPARTMENTAL-SPATIAL MODELING FRAMEWORK

    EPA Science Inventory

    An integrated hybrid spatial-compartmental modeling approach is presented for analyzing the dynamic distribution of chemicals in the multimedia environment. Information obtained from such analysis, which includes temporal chemical concentration profiles in various media, mass ...

  4. Transit times and mean ages for nonautonomous and autonomous compartmental systems

    DOE PAGES

    Rasmussen, Martin; Hastings, Alan; Smith, Matthew J.; Agusto, Folashade B.; Chen-Charpentier, Benito M.; Hoffman, Forrest M.; Jiang, Jiang; Todd-Brown, Katherine E. O.; Wang, Ying; Wang, Ying -Ping; et al

    2016-04-01

    In this study, we develop a theory for transit times and mean ages for nonautonomous compartmental systems. Using the McKendrick–von Förster equation, we show that the mean ages of mass in a compartmental system satisfy a linear nonautonomous ordinary differential equation that is exponentially stable. We then define a nonautonomous version of transit time as the mean age of mass leaving the compartmental system at a particular time and show that our nonautonomous theory generalises the autonomous case. We apply these results to study a nine-dimensional nonautonomous compartmental system modeling the terrestrial carbon cycle, which is a modification of themore » Carnegie–Ames–Stanford approach model, and we demonstrate that the nonautonomous versions of transit time and mean age differ significantly from the autonomous quantities when calculated for that model.« less

  5. Bidirectionality and compartmentation of metabolic fluxes are revealed in the dynamics of isotopomer networks.

    PubMed

    Schryer, David W; Peterson, Pearu; Paalme, Toomas; Vendelin, Marko

    2009-04-01

    Isotope labeling is one of the few methods of revealing the in vivo bidirectionality and compartmentalization of metabolic fluxes within metabolic networks. We argue that a shift from steady state to dynamic isotopomer analysis is required to deal with these cellular complexities and provide a review of dynamic studies of compartmentalized energy fluxes in eukaryotic cells including cardiac muscle, plants, and astrocytes. Knowledge of complex metabolic behaviour on a molecular level is prerequisite for the intelligent design of genetically modified organisms able to realize their potential of revolutionizing food, energy, and pharmaceutical production. We describe techniques to explore the bidirectionality and compartmentalization of metabolic fluxes using information contained in the isotopic transient, and discuss the integration of kinetic models with MFA. The flux parameters of an example metabolic network were optimized to examine the compartmentalization of metabolites and and the bidirectionality of fluxes in the TCA cycle of Saccharomyces uvarum for steady-state respiratory growth. PMID:19468334

  6. The R-Operon: A Model of Repetitive DNA-Organized Transcriptional Compartmentation of Eukaryotic Chromosomes for Coordinated Gene Expression

    PubMed Central

    Tang, Shao-Jun

    2016-01-01

    In eukaryotic genomes, it is essential to coordinate the activity of genes that function together to fulfill the same biological processes. Genomic organization likely plays a key role in coordinating transcription of different genes. However, little is known about how co-regulated genes are organized in the cell nucleus and how the chromosomal organization facilitates the co-regulation of different genes. I propose that eukaryotic genomes are organized into repeat assembly (RA)-based structural domains (“R-operons”) in the nuclear space. R-operons result from the interaction of homologous DNA repeats. In an R-operon, genes in different loci of the linear genome are brought into spatial vicinity and co-regulated by the same pool of transcription factors. This type of large-scale chromosomal organization may provide a mechanism for functional compartmentation of chromosomes to facilitate the transcriptional coordination of gene expression. PMID:27110825

  7. Multiple sampling and discriminatory fingerprinting reveals clonally complex and compartmentalized infections by M. bovis in cattle.

    PubMed

    Navarro, Yurena; Romero, Beatriz; Copano, María Francisca; Bouza, Emilio; Domínguez, Lucas; de Juan, Lucía; García-de-Viedma, Darío

    2015-01-30

    The combination of new genotyping tools and a more exhaustive sampling policy in the analysis of infection by Mycobacterium tuberculosis has shown that infection by this pathogen is more complex than initially expected. Mixed infections, coexistence of clonal variants from a parental strain, and compartmentalized infections are all different modalities of this clonal complexity. Until recently, genotyping of Mycobacterium bovis in animal populations was based on spoligotyping and analysis of a single isolate per infection; therefore, clonal complexity is probably underdetected. We used multiple sampling combined with highly discriminatory MIRU-VNTR to study compartmentalized infections by M. bovis in a low-tuberculosis prevalence setting. We spoligotyped the M. bovis isolates from two or more anatomic locations sampled from 55 animals on 39 independent farms. Compartmentalized infections, with two different strains infecting independent lymph nodes in the same animal, were found in six cases (10.9%). MIRU-VNTR analysis confirmed that the compartmentalization was strict and that only one strain was present in each infected node. MIRU-VNTR analysis of additional infected animals on one of the farms confirmed that the compartmentalized infection was a consequence of superinfection, since the two strains were independently infecting other animals. This same analysis revealed the emergence of a microevolved clonal variant in one of the lymph nodes of the compartmentalized animal. Clonal complexity must also be taken into consideration in M. bovis infection, even in low-prevalence settings, and analyses must be adapted to detect it and increase the accuracy of molecular epidemiology studies.

  8. In vivo compartmental analysis of leukocytes in mouse lungs.

    PubMed

    Patel, Brijesh V; Tatham, Kate C; Wilson, Michael R; O'Dea, Kieran P; Takata, Masao

    2015-10-01

    The lung has a unique structure consisting of three functionally different compartments (alveolar, interstitial, and vascular) situated in an extreme proximity. Current methods to localize lung leukocytes using bronchoalveolar lavage and/or lung perfusion have significant limitations for determination of location and phenotype of leukocytes. Here we present a novel method using in vivo antibody labeling to enable accurate compartmental localization/quantification and phenotyping of mouse lung leukocytes. Anesthetized C57BL/6 mice received combined in vivo intravenous and intratracheal labeling with fluorophore-conjugated anti-CD45 antibodies, and lung single-cell suspensions were analyzed by flow cytometry. The combined in vivo intravenous and intratracheal CD45 labeling enabled robust separation of the alveolar, interstitial, and vascular compartments of the lung. In naive mice, the alveolar compartment consisted predominantly of resident alveolar macrophages. The interstitial compartment, gated by events negative for both intratracheal and intravenous CD45 staining, showed two conventional dendritic cell populations, as well as a Ly6C(lo) monocyte population. Expression levels of MHCII on these interstitial monocytes were much higher than on the vascular Ly6C(lo) monocyte populations. In mice exposed to acid aspiration-induced lung injury, this protocol also clearly distinguished the three lung compartments showing the dynamic trafficking of neutrophils and exudative monocytes across the lung compartments during inflammation and resolution. This simple in vivo dual-labeling technique substantially increases the accuracy and depth of lung flow cytometric analysis, facilitates a more comprehensive examination of lung leukocyte pools, and enables the investigation of previously poorly defined "interstitial" leukocyte populations during models of inflammatory lung diseases.

  9. Compartmentation and complexation of metals in hyperaccumulator plants

    PubMed Central

    Leitenmaier, Barbara; Küpper, Hendrik

    2013-01-01

    Hyperaccumulators are being intensely investigated. They are not only interesting in scientific context due to their “strange” behavior in terms of dealing with high concentrations of metals, but also because of their use in phytoremediation and phytomining, for which understanding the mechanisms of hyperaccumulation is crucial. Hyperaccumulators naturally use metal accumulation as a defense against herbivores and pathogens, and therefore deal with accumulated metals in very specific ways of complexation and compartmentation, different from non-hyperaccumulator plants and also non-hyperaccumulated metals. For example, in contrast to non-hyperaccumulators, in hyperaccumulators even the classical phytochelatin-inducing metal, cadmium, is predominantly not bound by such sulfur ligands, but only by weak oxygen ligands. This applies to all hyperaccumulated metals investigated so far, as well as hyperaccumulation of the metalloid arsenic. Stronger ligands, as they have been shown to complex metals in non-hyperaccumulators, are in hyperaccumulators used for transient binding during transport to the storage sites (e.g., nicotianamine) and possibly for export of Cu in Cd/Zn hyperaccumulators [metallothioneins (MTs)]. This confirmed that enhanced active metal transport, and not metal complexation, is the key mechanism of hyperaccumulation. Hyperaccumulators tolerate the high amount of accumulated heavy metals by sequestering them into vacuoles, usually in large storage cells of the epidermis. This is mediated by strongly elevated expression of specific transport proteins in various tissues from metal uptake in the shoots up to the storage sites in the leaf epidermis. However, this mechanism seems to be very metal specific. Non-hyperaccumulated metals in hyperaccumulators seem to be dealt with like in non-hyperaccumulator plants, i.e., detoxified by binding to strong ligands such as MTs. PMID:24065978

  10. Compartmental intrathecal radioimmunotherapy: results for treatment for metastatic CNS neuroblastoma.

    PubMed

    Kramer, Kim; Kushner, Brian H; Modak, Shakeel; Pandit-Taskar, Neeta; Smith-Jones, Peter; Zanzonico, Pat; Humm, John L; Xu, Hong; Wolden, Suzanne L; Souweidane, Mark M; Larson, Steven M; Cheung, Nai-Kong V

    2010-05-01

    Innovation in the management of brain metastases is needed. We evaluated the addition of compartmental intrathecal antibody-based radioimmunotherapy (cRIT) in patients with recurrent metastatic central nervous system (CNS) neuroblastoma following surgery, craniospinal irradiation, and chemotherapy. Twenty one patients treated for recurrent neuroblastoma metastatic to the CNS, received a cRIT-containing salvage regimen incorporating intrathecal (131)I-monoclonal antibodies (MoAbs) targeting GD2 or B7H3 following surgery and radiation. Most patients also received outpatient craniospinal irradiation, 3F8/GMCSF immunotherapy, 13-cis-retinoic acid and oral temozolomide for systemic control. Seventeen of 21 cRIT-salvage patients are alive 7-74 months (median 33 months) since CNS relapse, with all 17 remaining free of CNS neuroblastoma. One patient died of infection at 22 months with no evidence of disease at autopsy, and one of lung and bone marrow metastases at 15 months, and one of progressive bone marrow disease at 30 months. The cRIT-salvage regimen was well tolerated, notable for myelosuppression minimized by stem cell support (n = 5), and biochemical hypothyroidism (n = 5). One patient with a 7-year history of metastatic neuroblastoma is in remission from MLL-associated secondary leukemia. This is significantly improved to published results with non-cRIT based where relapsed CNS NB has a median time to death of approximately 6 months. The cRIT-salvage regimen for CNS metastases was well tolerated by young patients, despite their prior history of intensive cytotoxic therapies. It has the potential to increase survival with better than expected quality of life.

  11. The compartmentation of phosphorylated thiamine derivatives in cultured neuroblastoma cells.

    PubMed

    Bettendorff, L

    1994-05-26

    Thiamine transport in cultured neuroblastoma cells is mediated by a high-affinity carrier (KM = 40 nM). In contrast, the uptake of the more hydrophobic sulbutiamine (isobutyrylthiamine disulfide) is unsaturable and its initial transport rate is 20-times faster than for thiamine. In the cytoplasm, sulbutiamine is rapidly hydrolyzed and reduced to free thiamine, the overall process resulting in a rapid and concentrative thiamine accumulation. Incorporation of radioactivity from [14C]thiamine or [14C]sulbutiamine into intracellular thiamine diphosphate is slow in both cases. Despite the fact that the diphosphate is probably the direct precursor for both thiamine monophosphate and triphosphate, the specific radioactivity increased much faster for the latter two compounds than for thiamine diphosphate. This suggests the existence of two pools of thiamine diphosphate, the larger one having a very slow turnover (about 17 h); a much smaller, rapidly turning over pool would be the precursor of thiamine mono- and triphosphate. The turnover time for thiamine triphosphate could be estimated to be 1-2 h. When preloading the cells with [14C]sulbutiamine was followed by a chase with the same concentration of the unlabeled compound, the specific radioactivities of thiamine and thiamine monophosphate decreased exponentially as expected, but labeling of the diphosphate continued to increase slowly. Specific radioactivity of thiamine triphosphate increased first, but after 30 min it began to slowly decrease. These results show for the first time the existence of distinct thiamine diphosphate pools in the same homogeneous cell population. They also suggest a complex compartmentation of thiamine metabolism. PMID:8186267

  12. Efficient Vaccine Distribution Based on a Hybrid Compartmental Model.

    PubMed

    Yu, Zhiwen; Liu, Jiming; Wang, Xiaowei; Zhu, Xianjun; Wang, Daxing; Han, Guoqiang

    2016-01-01

    To effectively and efficiently reduce the morbidity and mortality that may be caused by outbreaks of emerging infectious diseases, it is very important for public health agencies to make informed decisions for controlling the spread of the disease. Such decisions must incorporate various kinds of intervention strategies, such as vaccinations, school closures and border restrictions. Recently, researchers have paid increased attention to searching for effective vaccine distribution strategies for reducing the effects of pandemic outbreaks when resources are limited. Most of the existing research work has been focused on how to design an effective age-structured epidemic model and to select a suitable vaccine distribution strategy to prevent the propagation of an infectious virus. Models that evaluate age structure effects are common, but models that additionally evaluate geographical effects are less common. In this paper, we propose a new SEIR (susceptible-exposed-infectious šC recovered) model, named the hybrid SEIR-V model (HSEIR-V), which considers not only the dynamics of infection prevalence in several age-specific host populations, but also seeks to characterize the dynamics by which a virus spreads in various geographic districts. Several vaccination strategies such as different kinds of vaccine coverage, different vaccine releasing times and different vaccine deployment methods are incorporated into the HSEIR-V compartmental model. We also design four hybrid vaccination distribution strategies (based on population size, contact pattern matrix, infection rate and infectious risk) for controlling the spread of viral infections. Based on data from the 2009-2010 H1N1 influenza epidemic, we evaluate the effectiveness of our proposed HSEIR-V model and study the effects of different types of human behaviour in responding to epidemics. PMID:27233015

  13. Efficient Vaccine Distribution Based on a Hybrid Compartmental Model

    PubMed Central

    Yu, Zhiwen; Liu, Jiming; Wang, Xiaowei; Zhu, Xianjun; Wang, Daxing; Han, Guoqiang

    2016-01-01

    To effectively and efficiently reduce the morbidity and mortality that may be caused by outbreaks of emerging infectious diseases, it is very important for public health agencies to make informed decisions for controlling the spread of the disease. Such decisions must incorporate various kinds of intervention strategies, such as vaccinations, school closures and border restrictions. Recently, researchers have paid increased attention to searching for effective vaccine distribution strategies for reducing the effects of pandemic outbreaks when resources are limited. Most of the existing research work has been focused on how to design an effective age-structured epidemic model and to select a suitable vaccine distribution strategy to prevent the propagation of an infectious virus. Models that evaluate age structure effects are common, but models that additionally evaluate geographical effects are less common. In this paper, we propose a new SEIR (susceptible—exposed—infectious šC recovered) model, named the hybrid SEIR-V model (HSEIR-V), which considers not only the dynamics of infection prevalence in several age-specific host populations, but also seeks to characterize the dynamics by which a virus spreads in various geographic districts. Several vaccination strategies such as different kinds of vaccine coverage, different vaccine releasing times and different vaccine deployment methods are incorporated into the HSEIR-V compartmental model. We also design four hybrid vaccination distribution strategies (based on population size, contact pattern matrix, infection rate and infectious risk) for controlling the spread of viral infections. Based on data from the 2009–2010 H1N1 influenza epidemic, we evaluate the effectiveness of our proposed HSEIR-V model and study the effects of different types of human behaviour in responding to epidemics. PMID:27233015

  14. The secretory membrane system in the Drosophila syncytial blastoderm embryo exists as functionally compartmentalized units around individual nuclei

    PubMed Central

    Frescas, David; Mavrakis, Manos; Lorenz, Holger; DeLotto, Robert; Lippincott-Schwartz, Jennifer

    2006-01-01

    Drosophila melanogaster embryogenesis begins with 13 nuclear division cycles within a syncytium. This produces >6,000 nuclei that, during the next division cycle, become encased in plasma membrane in the process known as cellularization. In this study, we investigate how the secretory membrane system becomes equally apportioned among the thousands of syncytial nuclei in preparation for cellularization. Upon nuclear arrival at the cortex, the endoplasmic reticulum (ER) and Golgi were found to segregate among nuclei, with each nucleus becoming surrounded by a single ER/Golgi membrane system separate from adjacent ones. The nuclear-associated units of ER and Golgi across the syncytial blastoderm produced secretory products that were delivered to the plasma membrane in a spatially restricted fashion across the embryo. This occurred in the absence of plasma membrane boundaries between nuclei and was dependent on centrosome-derived microtubules. The emergence of secretory membranes that compartmentalized around individual nuclei in the syncytial blastoderm is likely to ensure that secretory organelles are equivalently partitioned among nuclei at cellularization and could play an important role in the establishment of localized gene and protein expression patterns within the early embryo. PMID:16636144

  15. Compartmentalization of proteinases and amylases in Nauphoeta cinerea midgut.

    PubMed

    Elpidina, E N; Vinokurov, K S; Gromenko, V A; Rudenskaya, Y A; Dunaevsky, Y E; Zhuzhikov, D P

    2001-12-01

    Compartmentalization of proteinases, amylases, and pH in the midgut of Nauphoeta cinerea Oliv. (Blattoptera:Blaberidae) was studied in order to understand the organization of protein and starch digestion. Total proteolytic activity measured with azocasein was maximal at pH 11.5 both in anterior (AM) and posterior (PM) halves of the midgut, but the bulk of activity (67%) was found in PM. Total AM and PM preparations were fractionated on a Sephadex G-50 column and further analysed by means of activity electrophoresis and specific inhibitors and activators. The major activity in PM was classified as an unusual SH-dependent proteinase with M(r) 24,000 and pH optimum with synthetic substrate BApNA at 10.0. The enzyme was 43-fold activated in the presence of 1 mM DTT, insensitive to synthetic inhibitors of serine (PMSF, TLCK, TPCK) and cysteine (IAA, E-64) proteinases, strongly inhibited by STI, and displayed four active bands on zymograms. In PM, activities of trypsin-like, chymotrypsin-like, subtilisin-like, and cysteine proteinases were observed. Aspartic and metalloproteinases were not detected. In AM, activity of unusual SH-dependent proteinase also dominated and activity of chymotrypsin-like proteinase was observed, but their levels were much lower than in PM. Distribution of amylase activity, exhibiting an optimum at pH 6.0, was quite the opposite. The major part of it (67%) was located in AM. Treatment of amylase preparation with proteinases from AM and PM reduced amylase activity twofold. pH of the midgut contents was 6.0-7.2 in AM, 6.4-7.6 in the first and 8.8-9.3 in the second halves of PM. Thus, pH in AM is in good agreement with the optimal pH of amylase, located in this compartment, but the activity of proteinases, including the ability to degrade amylase, in such an environment is low. Active proteolysis takes place in the second half of PM, where pH of the gut is close to the optimal pH of proteinases.

  16. Na+ compartmentalization related to salinity stress tolerance in upland cotton (Gossypium hirsutum) seedlings

    PubMed Central

    Peng, Zhen; He, Shoupu; Sun, Junling; Pan, Zhaoe; Gong, Wenfang; Lu, Yanli; Du, Xiongming

    2016-01-01

    The capacity for ion compartmentalization among different tissues and cells is the key mechanism regulating salt tolerance in plants. In this study, we investigated the ion compartmentalization capacity of two upland cotton genotypes with different salt tolerances under salt shock at the tissue, cell and molecular levels. We found that the leaf glandular trichome could secrete more salt ions in the salt-tolerant genotype than in the sensitive genotype, demonstrating the excretion of ions from tissue may be a new mechanism to respond to short-term salt shock. Furthermore, an investigation of the ion distribution demonstrated that the ion content was significantly lower in critical tissues and cells of the salt-tolerant genotype, indicating the salt-tolerant genotype had a greater capacity for ion compartmentalization in the shoot. By comparing the membrane H+-ATPase activity and the expression of ion transportation-related genes, we found that the H+-ATPase activity and Na+/H+ antiporter are the key factors determining the capacity for ion compartmentalization in leaves, which might further determine the salt tolerance of cotton. The novel function of the glandular trichome and the comparison of Na+ compartmentalization between two cotton genotypes with contrasting salt tolerances provide a new understanding of the salt tolerance mechanism in cotton. PMID:27698468

  17. Syntheses, crystal structures, and water adsorption behaviors of jungle-gym-type porous coordination polymers containing nitro moieties

    NASA Astrophysics Data System (ADS)

    Uemura, Kazuhiro; Onishi, Fumiaki; Yamasaki, Yukari; Kita, Hidetoshi

    2009-10-01

    NO 2 containing dicarboxylate bridging ligands, nitroterephthalate (bdc-NO 2) and 2,5-dinitroterephthalate (bdc-(NO 2) 2), afford porous coordination polymers, {[Zn 2(bdc-NO 2) 2(dabco)]· solvents} n ( 2⊃ solvents) and {[Zn 2(bdc-(NO 2) 2) 2(dabco)]· solvents} n ( 3⊃ solvents). Both compounds form jungle-gym-type regularities, where a 2D square grid composed of dinuclear Zn 2 units and dicarboxylate ligands is bridged by dabco molecules to extend the 2D layers into a 3D structure. In 2⊃ solvents and 3⊃ solvents, a rectangle pore surrounded by eight Zn 2 corners contains two and four NO 2 moieties, respectively. Thermal gravimetry (TG) and X-ray powder diffraction (XRPD) measurements reveal that both compounds maintain the frameworks regularities without guest molecules and with solvents such as MeOH, EtOH, i-PrOH, and Me 2CO. Adsorption measurements reveal that dried 2 and 3 adsorb H 2O molecules to be {[Zn 2(bdc-NO 2) 2(dabco)]·4H 2O} n ( 2⊃4H 2O) and {[Zn 2(bdc-(NO 2) 2) 2(dabco)]·6H 2O} n ( 3⊃6H 2O), showing the pore hydrophilicity enhancement caused by NO 2 group introduction.

  18. Molecular-level characterization of the breathing behavior of the jungle-gym-type DMOF-1 metal-organic framework.

    PubMed

    Grosch, Jason S; Paesani, Francesco

    2012-03-01

    Fundamental insights into the molecular mechanisms that determine the breathing behavior of the jungle-gym-type DMOF-1 metal-organic framework upon adsorption of benzene and isopropyl alcohol are gained from computer simulations. In all cases, good agreement is obtained between the calculated and experimental structural parameters. In the case of benzene adsorption, DMOF-1 is predicted to exist in a narrow pore configuration at high loadings and/or low temperature. A structural transition into a large pore configuration is then observed as the temperature increases and/or the loading decreases, which is directly related to the spatial distribution and molecular interactions of the benzene molecules within the pores. The isopropyl alcohol adsorption simulations indicate that DMOF-1 undergoes two distinct structural transitions (from large pore to narrow pore and then back to large pore) as the number of adsorbed molecules increases, which is explained in terms of the formation of hydrogen bonds between the isopropyl molecules and the framework.

  19. Compartmentalization of incompatible reagents within Pickering emulsion droplets for one-pot cascade reactions.

    PubMed

    Yang, Hengquan; Fu, Luman; Wei, Lijuan; Liang, Jifen; Binks, Bernard P

    2015-01-28

    It is a dream that future synthetic chemistry can mimic living systems to process multistep cascade reactions in a one-pot fashion. One of the key challenges is the mutual destruction of incompatible or opposing reagents, for example, acid and base, oxidants and reductants. A conceptually novel strategy is developed here to address this challenge. This strategy is based on a layered Pickering emulsion system, which is obtained through lamination of Pickering emulsions. In this working Pickering emulsion, the dispersed phase can separately compartmentalize the incompatible reagents to avoid their mutual destruction, while the continuous phase allows other reagent molecules to diffuse freely to access the compartmentalized reagents for chemical reactions. The compartmentalization effects and molecular transport ability of the Pickering emulsion were investigated. The deacetalization-reduction, deacetalization-Knoevenagel, deacetalization-Henry and diazotization-iodization cascade reactions demonstrate well the versatility and flexibility of our strategy in processing the one-pot cascade reactions involving mutually destructive reagents.

  20. Preventing Age-Related Decline of Gut Compartmentalization Limits Microbiota Dysbiosis and Extends Lifespan.

    PubMed

    Li, Hongjie; Qi, Yanyan; Jasper, Heinrich

    2016-02-10

    Compartmentalization of the gastrointestinal (GI) tract of metazoans is critical for health. GI compartments contain specific microbiota, and microbiota dysbiosis is associated with intestinal dysfunction. Dysbiosis develops in aging intestines, yet how this relates to changes in GI compartmentalization remains unclear. The Drosophila GI tract is an accessible model to address this question. Here we show that the stomach-like copper cell region (CCR) in the middle midgut controls distribution and composition of the microbiota. We find that chronic activation of JAK/Stat signaling in the aging gut induces a metaplasia of the gastric epithelium, CCR decline, and subsequent commensal dysbiosis and epithelial dysplasia along the GI tract. Accordingly, inhibition of JAK/Stat signaling in the CCR specifically prevents age-related metaplasia, commensal dysbiosis and functional decline in old guts, and extends lifespan. Our results establish a mechanism by which age-related chronic inflammation causes the decline of intestinal compartmentalization and microbiota dysbiosis, limiting lifespan. PMID:26867182

  1. Preventing Age-Related Decline of Gut Compartmentalization Limits Microbiota Dysbiosis and Extends Lifespan.

    PubMed

    Li, Hongjie; Qi, Yanyan; Jasper, Heinrich

    2016-02-10

    Compartmentalization of the gastrointestinal (GI) tract of metazoans is critical for health. GI compartments contain specific microbiota, and microbiota dysbiosis is associated with intestinal dysfunction. Dysbiosis develops in aging intestines, yet how this relates to changes in GI compartmentalization remains unclear. The Drosophila GI tract is an accessible model to address this question. Here we show that the stomach-like copper cell region (CCR) in the middle midgut controls distribution and composition of the microbiota. We find that chronic activation of JAK/Stat signaling in the aging gut induces a metaplasia of the gastric epithelium, CCR decline, and subsequent commensal dysbiosis and epithelial dysplasia along the GI tract. Accordingly, inhibition of JAK/Stat signaling in the CCR specifically prevents age-related metaplasia, commensal dysbiosis and functional decline in old guts, and extends lifespan. Our results establish a mechanism by which age-related chronic inflammation causes the decline of intestinal compartmentalization and microbiota dysbiosis, limiting lifespan.

  2. A Computational Modeling and Simulation Approach to Investigate Mechanisms of Subcellular cAMP Compartmentation.

    PubMed

    Yang, Pei-Chi; Boras, Britton W; Jeng, Mao-Tsuen; Docken, Steffen S; Lewis, Timothy J; McCulloch, Andrew D; Harvey, Robert D; Clancy, Colleen E

    2016-07-01

    Subcellular compartmentation of the ubiquitous second messenger cAMP has been widely proposed as a mechanism to explain unique receptor-dependent functional responses. How exactly compartmentation is achieved, however, has remained a mystery for more than 40 years. In this study, we developed computational and mathematical models to represent a subcellular sarcomeric space in a cardiac myocyte with varying detail. We then used these models to predict the contributions of various mechanisms that establish subcellular cAMP microdomains. We used the models to test the hypothesis that phosphodiesterases act as functional barriers to diffusion, creating discrete cAMP signaling domains. We also used the models to predict the effect of a range of experimentally measured diffusion rates on cAMP compartmentation. Finally, we modeled the anatomical structures in a cardiac myocyte diad, to predict the effects of anatomical diffusion barriers on cAMP compartmentation. When we incorporated experimentally informed model parameters to reconstruct an in silico subcellular sarcomeric space with spatially distinct cAMP production sites linked to caveloar domains, the models predict that under realistic conditions phosphodiesterases alone were insufficient to generate significant cAMP gradients. This prediction persisted even when combined with slow cAMP diffusion. When we additionally considered the effects of anatomic barriers to diffusion that are expected in the cardiac myocyte dyadic space, cAMP compartmentation did occur, but only when diffusion was slow. Our model simulations suggest that additional mechanisms likely contribute to cAMP gradients occurring in submicroscopic domains. The difference between the physiological and pathological effects resulting from the production of cAMP may be a function of appropriate compartmentation of cAMP signaling. Therefore, understanding the contribution of factors that are responsible for coordinating the spatial and temporal

  3. A Computational Modeling and Simulation Approach to Investigate Mechanisms of Subcellular cAMP Compartmentation

    PubMed Central

    Yang, Pei-Chi; Boras, Britton W.; Jeng, Mao-Tsuen; Lewis, Timothy J.; McCulloch, Andrew D.; Harvey, Robert D.; Clancy, Colleen E.

    2016-01-01

    Subcellular compartmentation of the ubiquitous second messenger cAMP has been widely proposed as a mechanism to explain unique receptor-dependent functional responses. How exactly compartmentation is achieved, however, has remained a mystery for more than 40 years. In this study, we developed computational and mathematical models to represent a subcellular sarcomeric space in a cardiac myocyte with varying detail. We then used these models to predict the contributions of various mechanisms that establish subcellular cAMP microdomains. We used the models to test the hypothesis that phosphodiesterases act as functional barriers to diffusion, creating discrete cAMP signaling domains. We also used the models to predict the effect of a range of experimentally measured diffusion rates on cAMP compartmentation. Finally, we modeled the anatomical structures in a cardiac myocyte diad, to predict the effects of anatomical diffusion barriers on cAMP compartmentation. When we incorporated experimentally informed model parameters to reconstruct an in silico subcellular sarcomeric space with spatially distinct cAMP production sites linked to caveloar domains, the models predict that under realistic conditions phosphodiesterases alone were insufficient to generate significant cAMP gradients. This prediction persisted even when combined with slow cAMP diffusion. When we additionally considered the effects of anatomic barriers to diffusion that are expected in the cardiac myocyte dyadic space, cAMP compartmentation did occur, but only when diffusion was slow. Our model simulations suggest that additional mechanisms likely contribute to cAMP gradients occurring in submicroscopic domains. The difference between the physiological and pathological effects resulting from the production of cAMP may be a function of appropriate compartmentation of cAMP signaling. Therefore, understanding the contribution of factors that are responsible for coordinating the spatial and temporal

  4. Metabolism and possible compartmentalization of inositol lipids in isolated rat-liver nuclei.

    PubMed Central

    Vann, L R; Wooding, F B; Irvine, R F; Divecha, N

    1997-01-01

    radiolabelled pools of PtdIns(4)P and PtdIns(4,5)P2. This was confirmed by analysis of the incorporation of 32P into the 4'-phosphate group of PtdIns(4)P and the individual 4'- and 5'-phosphate groups of PtdIns(4,5)P2. The data from these experiments also indicated that PtdIns(4,5)P2 can be produced from a pre-existing pool of PtdIns(4)P, as well as de novo from PtdIns. (7) Taken together our data suggest that isolated rat-liver nuclei have an intranuclear inositol lipid metabolism mechanism utilizing enzymes and substrates equivalent to those found in cytosol and plasma membrane, and that there may be some, but not complete, compartmentalization of the components of the nuclear inositol cycle. PMID:9359431

  5. 21 CFR 888.3535 - Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .../polymer porous-coated uncemented prosthesis. 888.3535 Section 888.3535 Food and Drugs FOOD AND DRUG... Devices § 888.3535 Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis. (a) Identification. A knee joint femorotibial (uni-compartmental) metal/polymer...

  6. 21 CFR 888.3535 - Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... across-the-joint. This generic type of device is designed to achieve biological fixation to bone without... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Knee joint femorotibial (uni-compartmental) metal... Devices § 888.3535 Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated...

  7. 21 CFR 888.3535 - Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... across-the-joint. This generic type of device is designed to achieve biological fixation to bone without... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Knee joint femorotibial (uni-compartmental) metal... Devices § 888.3535 Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated...

  8. 21 CFR 888.3535 - Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .../polymer porous-coated uncemented prosthesis. 888.3535 Section 888.3535 Food and Drugs FOOD AND DRUG... Devices § 888.3535 Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis. (a) Identification. A knee joint femorotibial (uni-compartmental) metal/polymer...

  9. 21 CFR 888.3535 - Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .../polymer porous-coated uncemented prosthesis. 888.3535 Section 888.3535 Food and Drugs FOOD AND DRUG... Devices § 888.3535 Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis. (a) Identification. A knee joint femorotibial (uni-compartmental) metal/polymer...

  10. A-kinase anchoring proteins: cAMP compartmentalization in neurodegenerative and obstructive pulmonary diseases

    PubMed Central

    Poppinga, W J; Muñoz-Llancao, P; González-Billault, C; Schmidt, M

    2014-01-01

    The universal second messenger cAMP is generated upon stimulation of Gs protein-coupled receptors, such as the β2-adreneoceptor, and leads to the activation of PKA, the major cAMP effector protein. PKA oscillates between an on and off state and thereby regulates a plethora of distinct biological responses. The broad activation pattern of PKA and its contribution to several distinct cellular functions lead to the introduction of the concept of compartmentalization of cAMP. A-kinase anchoring proteins (AKAPs) are of central importance due to their unique ability to directly and/or indirectly interact with proteins that either determine the cellular content of cAMP, such as β2-adrenoceptors, ACs and PDEs, or are regulated by cAMP such as the exchange protein directly activated by cAMP. We report on lessons learned from neurons indicating that maintenance of cAMP compartmentalization by AKAP5 is linked to neurotransmission, learning and memory. Disturbance of cAMP compartments seem to be linked to neurodegenerative disease including Alzheimer's disease. We translate this knowledge to compartmentalized cAMP signalling in the lung. Next to AKAP5, we focus here on AKAP12 and Ezrin (AKAP78). These topics will be highlighted in the context of the development of novel pharmacological interventions to tackle AKAP-dependent compartmentalization. PMID:25132049

  11. Technology Solutions Case Study: Field Testing of Compartmentalization Methods for Multifamily Construction

    SciTech Connect

    2015-01-01

    Fire-resistance rated (or area separation) wall assemblies present a great difficulty in air sealing/compartmentalization, particularly in townhouse construction. To address this challenge, Building Science Corporation partnered with builder K. Hovnanian Homes to determine whether taping exterior sheathing details improves air sealing in townhouse and multifamily construction, and to better understand air leakage pathways.

  12. Beyond Compartmentalization: A Relational Approach towards Agency and Vulnerability of Young Migrants

    ERIC Educational Resources Information Center

    Huijsmans, Roy

    2012-01-01

    Based on fieldwork material from Lao People's Democratic Republic, this paper introduces an analytical framework that transcends compartmentalized approaches towards migration involving young people. The notions of fluid and institutionalized forms of migration illuminate key differences and commonalities in the relational fabric underpinning…

  13. Origin of reservoir compartmentalization in Lower Ordovician Karstic Dolostones, Ellenburger Group, West Texas

    SciTech Connect

    Kerans, C.

    1988-01-01

    Ellenburger Group reservoirs constitute a major play in the Permian basin of west Texas, with over 1.4 billion bbl cumulative production through 1985. These reservoirs typically have been developed by assuming homogeneous fracture-related pore system. Examination of core, log, and production data demonstrates that most Ellenburger reservoirs are characterized by pronounced vertical and lateral heterogeneities created by post-Ellenburger karst development. Vertical reservoir compartmentalization in the Ellenburger evolved from development of a laterally extensive cave system between 100 and 300 ft beneath the original land surface. Caves were filled by relatively impermeable siliciclastics from the overlying Simpson Group, effectively isolating permeable cave-roof breccias (uppermost Ellenburger) from collapse breccias deposited on cave floors prior to shale infill. Lateral compartmentalization of Ellenburger reservoirs originated by localized collapse of the cave system both during karst formation and after burial. In the Shafter Lake field, lateral compartmentalization is the result of a 200-ft vertical collapse during deposition of Simpson Group sands. Abrupt lateral discontinuities in the Big Lake and Glasco fields may represent similar collapse-related features, such as are spectacularly displayed in Ellenburger-equivalent outcrops of the Franklin Mountains. An estimated 750 million bbl of remaining mobile oil, in addition to conventional reserves, occurs in this mature but complexly compartmentalized play. Considering this paleokarst model will aid in further exploitation of Ellenburger reservoirs.

  14. Krebs cycle metabolon formation: metabolite concentration gradient enhanced compartmentation of sequential enzymes.

    PubMed

    Wu, Fei; Pelster, Lindsey N; Minteer, Shelley D

    2015-01-25

    Dynamics of metabolon formation in mitochondria was probed by studying diffusional motion of two sequential Krebs cycle enzymes in a microfluidic channel. Enhanced directional co-diffusion of both enzymes against a substrate concentration gradient was observed in the presence of intermediate generation. This reveals a metabolite directed compartmentation of metabolic pathways.

  15. SYNCHROTRON X-RAY ABSORPTION-EDGE COMPUTED MICROTOMOGRAPHY IMAGING OF THALLIUM COMPARTMENTALIZATION IN IBERIS INTERMEDIA

    EPA Science Inventory

    Thallium (TI) is an extremely toxic metal which, due to its similarities to K, is readily taken up by plants. Thallium is efficiently hyperaccumulated in Iberis intermedia as TI(I). Distribution and compartmentalization of TI in I. intermedia is highes...

  16. Jesús and María in the jungle: an essay on possibility and constraint in the third-shift third space

    NASA Astrophysics Data System (ADS)

    Richardson Bruna, Katherine

    2009-03-01

    One hundred years ago, Upton Sinclair, in The Jungle, exposed the deplorable working conditions of eastern European immigrants in the meatpacking houses of Chicago. The backdrop of this article is the new Jungle of the 21st century—the hog plants of the rural Midwest. Here I speak to the lives of the Mexican workers they employ, and, more specifically, the science-learning experiences and aspirations of third-shifters, Jesús and María. I use these students' stories as an opportunity to examine the take-up, in education, of the concept of hybridity, and, more particularly, to interrogate what I have come to regard as the "third space fetish." My principle argument is that Bhabha's understanding of liberatory Third Space has been distorted, in education, through teacher-centered and power-neutral multicultural discourse. I call for a more robust approach to hybridity in science education research, guided by the lessons of possibility and constraint contained in Jesús' and María's third-shift third space lives.

  17. The relationship of natural and artificial maturation: Evidence for pressure compartmentalization, and for coal as a source of petroleum

    SciTech Connect

    MacGowan, D.B.; Britton, D.R.; Surdam, R.C. . Dept. of Geology and Geophysics)

    1992-01-01

    In the Greater Green River Basin (GRB), the Almond Fm. is an important reservoir, having yielded cumulative production of 100 MBO and 0.7 TCFG through 1986. A regional study of Almond Fm. shales and coals in wells from the northwestern to the southeastern GRB was undertaken. Core samples from the Almond Fm. were subjected to: anhydrous pyrolysis, total organic carbon, vitrinite reflectance, and nuclear magnetic resonance analyses. The Almond appears to be a moderate to rich source rock, and in the oil window over the depth range of sampling (4,500 - 14,500 ft.). Additionally, a series of hydrous pyrolysis experiments were conducted on Almond coal samples at temperatures of 290 to 360 C. The organic-geochemical analyses performed on the core samples were also performed on these coal samples. These experiments show that Almond coal may be a significant source of liquid hydrocarbons (27 mg oil/g coal) as well as a prolific source of natural gas (7.52 x 10[sup [minus]6] moles natural gas/g coal). Gas production from tight gas sands accounts for about 20% of gas production from the Almond; almost all of this production is from overpressured reservoirs that produce little or not water, conditions characteristic of compartmentalized, abnormally-pressured sandstones. Comparison of maturation trends observed in the well core data with the hydrous pyrolysis data suggest that this mechanism also may operate in the Almond Fm. in the GRB.

  18. Compartmentalization role of A-kinase anchoring proteins (AKAPs) in mediating protein kinase A (PKA) signaling and cardiomyocyte hypertrophy.

    PubMed

    Rababa'h, Abeer; Singh, Sonal; Suryavanshi, Santosh V; Altarabsheh, Salah Eldien; Deo, Salil V; McConnell, Bradley K

    2014-12-24

    The Beta-adrenergic receptors (β-ARs) stimulation enhances contractility through protein kinase-A (PKA) substrate phosphorylation. This PKA signaling is conferred in part by PKA binding to A-kinase anchoring proteins (AKAPs). AKAPs coordinate multi-protein signaling networks that are targeted to specific intracellular locations, resulting in the localization of enzyme activity and transmitting intracellular actions of neurotransmitters and hormones to its target substrates. In particular, mAKAP (muscle-selective AKAP) has been shown to be present on the nuclear envelope of cardiomyocytes with various proteins including: PKA-regulatory subunit (RIIα), phosphodiesterase-4D3, protein phosphatase-2A, and ryanodine receptor (RyR2). Therefore, through the coordination of spatial-temporal signaling of proteins and enzymes, mAKAP controls cyclic-adenosine monophosphate (cAMP) levels very tightly and functions as a regulator of PKA-mediated substrate phosphorylation leading to changes in calcium availability and myofilament calcium sensitivity. The goal of this review is to elucidate the critical compartmentalization role of mAKAP in mediating PKA signaling and regulating cardiomyocyte hypertrophy by acting as a scaffolding protein. Based on our literature search and studying the structure-function relationship between AKAP scaffolding protein and its binding partners, we propose possible explanations for the mechanism by which mAKAP promotes cardiac hypertrophy.

  19. The cell cycle of the planctomycete Gemmata obscuriglobus with respect to cell compartmentalization

    PubMed Central

    Lee, Kuo-Chang; Webb, Rick I; Fuerst, John A

    2009-01-01

    Background Gemmata obscuriglobus is a distinctive member of the divergent phylum Planctomycetes, all known members of which are peptidoglycan-less bacteria with a shared compartmentalized cell structure and divide by a budding process. G. obscuriglobus in addition shares the unique feature that its nucleoid DNA is surrounded by an envelope consisting of two membranes forming an analogous structure to the membrane-bounded nucleoid of eukaryotes and therefore G. obscuriglobus forms a special model for cell biology. Draft genome data for G. obscuriglobus as well as complete genome sequences available so far for other planctomycetes indicate that the key bacterial cell division protein FtsZ is not present in these planctomycetes, so the cell division process in planctomycetes is of special comparative interest. The membrane-bounded nature of the nucleoid in G. obscuriglobus also suggests that special mechanisms for the distribution of this nuclear body to the bud and for distribution of chromosomal DNA might exist during division. It was therefore of interest to examine the cell division cycle in G. obscuriglobus and the process of nucleoid distribution and nuclear body formation during division in this planctomycete bacterium via light and electron microscopy. Results Using phase contrast and fluorescence light microscopy, and transmission electron microscopy, the cell division cycle of G. obscuriglobus was determined. During the budding process, the bud was formed and developed in size from one point of the mother cell perimeter until separation. The matured daughter cell acted as a new mother cell and started its own budding cycle while the mother cell can itself initiate budding repeatedly. Fluorescence microscopy of DAPI-stained cells of G. obscuriglobus suggested that translocation of the nucleoid and formation of the bud did not occur at the same time. Confocal laser scanning light microscopy applied to cells stained for membranes as well as DNA confirmed the

  20. The effect of simultaneous internal tamponade on fluid compartmentalization and its relationship to cell proliferation.

    PubMed

    De Molfetta, V; Bottoni, F; Arpa, P; Vinciguerra, P; Zenoni, S

    1992-01-01

    To determine whether the residual free spaces within the vitreous chamber that result after vitreoretinal surgery and internal tamponade may be avoided, and to verify whether such compartmentalization is of real importance in the recurrence of postoperative proliferative vitreoretinopathy (PVR), the use of simultaneous double filling with polydimethylsiloxane (PDMS) and fluorosilicone (FSiO) in the repair of complicated retinal detachment is evaluated in 12 selected cases. Initial retinal reattachment was achieved in all cases. PVR recurred in 10 patients (83%), 6 of whom showed partial retinal detachment. Inferior and superior postoperative residual free spaces were abolished by this procedure, but a new residual fluid space was created, lying horizontally between the bubbles and expanding in a triangular shape nasal to the optic disc and temporal to the macula. Overall, 9 of 10 eyes with PVR after surgery had proliferation involving these areas. These findings support the concept that compartmentalization is of major importance in determining postoperative cell proliferation.

  1. The MATCHIT Automaton: Exploiting Compartmentalization for the Synthesis of Branched Polymers

    PubMed Central

    Weyland, Mathias S.; Fellermann, Harold; Hadorn, Maik; Sorek, Daniel; Lancet, Doron; Rasmussen, Steen; Füchslin, Rudolf M.

    2013-01-01

    We propose an automaton, a theoretical framework that demonstrates how to improve the yield of the synthesis of branched chemical polymer reactions. This is achieved by separating substeps of the path of synthesis into compartments. We use chemical containers (chemtainers) to carry the substances through a sequence of fixed successive compartments. We describe the automaton in mathematical terms and show how it can be configured automatically in order to synthesize a given branched polymer target. The algorithm we present finds an optimal path of synthesis in linear time. We discuss how the automaton models compartmentalized structures found in cells, such as the endoplasmic reticulum and the Golgi apparatus, and we show how this compartmentalization can be exploited for the synthesis of branched polymers such as oligosaccharides. Lastly, we show examples of artificial branched polymers and discuss how the automaton can be configured to synthesize them with maximal yield. PMID:24489601

  2. Self-Assembly and Compartmentalization of Nanozymes in Mesoporous Silica-Based Nanoreactors.

    PubMed

    Huang, Yanyan; Lin, Youhui; Ran, Xiang; Ren, Jinsong; Qu, Xiaogang

    2016-04-11

    Herein, to mimic complex natural system, polyelectrolyte multilayer (PEM)-coated mesoporous silica nanoreactors were used to compartmentalize two different artificial enzymes. PEMs coated on the surface of mesoporous silica could serve as a permeable membrane to control the flow of molecules. When assembling hemin on the surface of mesoporous silica, the hemin-based mesoporous silica system possessed remarkable peroxidase-like activity, especially at physiological pH, and could be recycled more easily than traditional graphene-hemin nanocompounds. The hope is that these new findings may pave the way for exploring novel nanoreactors to achieve compartmentalization of nanozymes and applying artificial cascade catalytic systems to mimic cell organelles or important biochemical transformations.

  3. Structurally controlled and aligned tight gas reservoir compartmentalization in the San Juan and Piceance Basins

    SciTech Connect

    Decker, A.D.; Kuuskraa, V.A.; Klawitter, A.L.

    1995-10-01

    Recurrent basement faulting is the primary controlling mechanism for aligning and compartmentalizing upper Cretaceous aged tight gas reservoirs of the San Juan and Piceance Basins. Northwest trending structural lineaments that formed in conjunction with the Uncompahgre Highlands have profoundly influenced sedimentation trends and created boundaries for gas migration; sealing and compartmentalizing sedimentary packages in both basins. Fractures which formed over the structural lineaments provide permeability pathways which allowing gas recovery from otherwise tight gas reservoirs. Structural alignments and associated reservoir compartments have been accurately targeted by integrating advanced remote sensing imagery, high resolution aeromagnetics, seismic interpretation, stratigraphic mapping and dynamic structural modelling. This unifying methodology is a powerful tool for exploration geologists and is also a systematic approach to tight gas resource assessment in frontier basins.

  4. Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation.

    PubMed

    Kreft, Marko; Bak, Lasse K; Waagepetersen, Helle S; Schousboe, Arne

    2012-04-27

    Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation.

  5. Bioinspired genotype–phenotype linkages: mimicking cellular compartmentalization for the engineering of functional proteins

    PubMed Central

    van Vliet, Liisa D.; Colin, Pierre-Yves; Hollfelder, Florian

    2015-01-01

    The idea of compartmentalization of genotype and phenotype in cells is key for enabling Darwinian evolution. This contribution describes bioinspired systems that use in vitro compartments—water-in-oil droplets and gel-shell beads—for the directed evolution of functional proteins. Technologies based on these principles promise to provide easier access to protein-based therapeutics, reagents for processes involving enzyme catalysis, parts for synthetic biology and materials with biological components. PMID:26464791

  6. The effect of body position on compartmental intra-abdominal pressure following liver transplantation

    PubMed Central

    2012-01-01

    Background Current assumptions rely on intra-abdominal pressure (IAP) being uniform across the abdominal cavity. The abdominal contents are, however, a heterogeneous mix of solid, liquid and gas, and pressure transmission may not be uniform. The current study examines the upper and lower IAP following liver transplantation. Methods IAP was measured directly via intra-peritoneal catheters placed at the liver and outside the bladder. Compartmental pressure data were recorded at 10-min intervals for up to 72 h following surgery, and the effect of intermittent posture change on compartmental pressures was also studied. Pelvic intra-peritoneal pressure was compared to intra-bladder pressure measured via a FoleyManometer. Results A significant variation in upper and lower IAP of 18% was observed with a range of differences of 0 to 16 mmHg. A sustained difference in inter-compartmental pressure of 4 mmHg or more was present for 23% of the study time. Head-up positioning at 30° provided a protective effect on upper intra-abdominal pressure, resulting in a significant reduction in all patients. There was excellent agreement between intra-bladder and pelvic pressure. Conclusions A clinically significant variation in inter-compartmental pressure exists following liver transplantation, which can be manipulated by changes to body position. The existence of regional pressure differences suggests that IAP monitoring at the bladder alone may under-diagnose intra-abdominal hypertension and abdominal compartment syndrome in these patients. The upper and lower abdomen may need to be considered as separate entities in certain conditions. PMID:22873413

  7. Combined Noninvasive Imaging and Modeling Approaches Reveal Metabolic Compartmentation in the Barley Endosperm[W][OA

    PubMed Central

    Rolletschek, Hardy; Melkus, Gerd; Grafahrend-Belau, Eva; Fuchs, Johannes; Heinzel, Nicolas; Schreiber, Falk; Jakob, Peter M.; Borisjuk, Ljudmilla

    2011-01-01

    The starchy endosperm of cereals is a priori taken as a metabolically uniform tissue. By applying a noninvasive assay based on 13C/1H-magnetic resonance imaging (MRI) to barley (Hordeum vulgare) grains, we uncovered metabolic compartmentation in the endosperm. 13C-Suc feeding during grain filling showed that the primary site of Ala synthesis was the central region of the endosperm, the part of the caryopsis experiencing the highest level of hypoxia. Region-specific metabolism in the endosperm was characterized by flux balance analysis (FBA) and metabolite profiling. FBA predicts that in the central region of the endosperm, the tricarboxylic acid cycle shifts to a noncyclic mode, accompanied by elevated glycolytic flux and the accumulation of Ala. The metabolic compartmentation within the endosperm is advantageous for the grain's carbon and energy economy, with a prominent role being played by Ala aminotransferase. An investigation of caryopses with a genetically perturbed tissue pattern demonstrated that Ala accumulation is a consequence of oxygen status, rather than being either tissue specific or dependent on the supply of Suc. Hence the 13C-Ala gradient can be used as an in vivo marker for hypoxia. The combination of MRI and metabolic modeling offers opportunities for the noninvasive analysis of metabolic compartmentation in plants. PMID:21856793

  8. Mapping intracellular diffusion distribution using single quantum dot tracking: compartmentalized diffusion defined by endoplasmic reticulum.

    PubMed

    Li, Hui; Dou, Shuo-Xing; Liu, Yu-Ru; Li, Wei; Xie, Ping; Wang, Wei-Chi; Wang, Peng-Ye

    2015-01-14

    The crowded intracellular environment influences the diffusion-mediated cellular processes, such as metabolism, signaling, and transport. The hindered diffusion of macromolecules in heterogeneous cytoplasm has been studied over years, but the detailed diffusion distribution and its origin still remain unclear. Here, we introduce a novel method to map rapidly the diffusion distribution in single cells based on single-particle tracking (SPT) of quantum dots (QDs). The diffusion map reveals the heterogeneous intracellular environment and, more importantly, an unreported compartmentalization of QD diffusions in cytoplasm. Simultaneous observations of QD motion and green fluorescent protein-tagged endoplasmic reticulum (ER) dynamics provide direct evidence that the compartmentalization results from micron-scale domains defined by ER tubules, and ER cisternae form perinuclear areas that restrict QDs to enter. The same phenomenon was observed using fluorescein isothiocyanate-dextrans, further confirming the compartmentalized diffusion. These results shed new light on the diffusive movements of macromolecules in the cell, and the mapping of intracellular diffusion distribution may be used to develop strategies for nanoparticle-based drug deliveries and therapeutics.

  9. The mechanics of cellular compartmentalization as a model for tumor spreading

    NASA Astrophysics Data System (ADS)

    Fritsch, Anatol; Pawlizak, Steve; Zink, Mareike; Kaes, Josef A.

    2012-02-01

    Based on a recently developed surgical method of Michael H"ockel, which makes use of cellular confinement to compartments in the human body, we study the mechanics of the process of cell segregation. Compartmentalization is a fundamental process of cellular organization and occurs during embryonic development. A simple model system can demonstrate the process of compartmentalization: When two populations of suspended cells are mixed, this mixture will eventually segregate into two phases, whereas mixtures of the same cell type will not. In the 1960s, Malcolm S. Steinberg formulated the so-called differential adhesion hypothesis which explains the segregation in the model system and the process of compartmentalization by differences in surface tension and adhesiveness of the interacting cells. We are interested in to which extend the same physical principles affect tumor growth and spreading between compartments. For our studies, we use healthy and cancerous breast cell lines of different malignancy as well as primary cells from human cervix carcinoma. We apply a set of techniques to study their mechanical properties and interactions. The Optical Stretcher is used for whole cell rheology, while Cell-cell-adhesion forces are directly measured with a modified AFM. In combination with 3D segregation experiments in droplet cultures we try to clarify the role of surface tension in tumor spreading.

  10. Verification of Compartmental Epidemiological Models using Metamorphic Testing, Model Checking and Visual Analytics

    SciTech Connect

    Ramanathan, Arvind; Steed, Chad A; Pullum, Laura L

    2012-01-01

    Compartmental models in epidemiology are widely used as a means to model disease spread mechanisms and understand how one can best control the disease in case an outbreak of a widespread epidemic occurs. However, a significant challenge within the community is in the development of approaches that can be used to rigorously verify and validate these models. In this paper, we present an approach to rigorously examine and verify the behavioral properties of compartmen- tal epidemiological models under several common modeling scenarios including birth/death rates and multi-host/pathogen species. Using metamorphic testing, a novel visualization tool and model checking, we build a workflow that provides insights into the functionality of compartmental epidemiological models. Our initial results indicate that metamorphic testing can be used to verify the implementation of these models and provide insights into special conditions where these mathematical models may fail. The visualization front-end allows the end-user to scan through a variety of parameters commonly used in these models to elucidate the conditions under which an epidemic can occur. Further, specifying these models using a process algebra allows one to automatically construct behavioral properties that can be rigorously verified using model checking. Taken together, our approach allows for detecting implementation errors as well as handling conditions under which compartmental epidemiological models may fail to provide insights into disease spread dynamics.

  11. Diminished viral replication and compartmentalization of hepatitis C virus in hepatocellular carcinoma tissue

    PubMed Central

    Harouaka, Djamila; Engle, Ronald E.; Wollenberg, Kurt; Diaz, Giacomo; Tice, Ashley B.; Zamboni, Fausto; Govindarajan, Sugantha; Alter, Harvey; Kleiner, David E.; Farci, Patrizia

    2016-01-01

    Analysis of hepatitis C virus (HCV) replication and quasispecies distribution within the tumor of patients with HCV-associated hepatocellular carcinoma (HCC) can provide insight into the role of HCV in hepatocarcinogenesis and, conversely, the effect of HCC on the HCV lifecycle. In a comprehensive study of serum and multiple liver specimens from patients with HCC who underwent liver transplantation, we found a sharp and significant decrease in HCV RNA in the tumor compared with surrounding nontumorous tissues, but found no differences in multiple areas of control non-HCC cirrhotic livers. Diminished HCV replication was not associated with changes in miR-122 expression. HCV genetic diversity was significantly higher in livers containing HCC compared with control non-HCC cirrhotic livers. Tracking of individual variants demonstrated changes in the viral population between tumorous and nontumorous areas, the extent of which correlated with the decline in HCV RNA, suggesting HCV compartmentalization within the tumor. In contrast, compartmentalization was not observed between nontumorous areas and serum, or in controls between different areas of the cirrhotic liver or between liver and serum. Our findings indicate that HCV replication within the tumor is restricted and compartmentalized, suggesting segregation of specific viral variants in malignant hepatocytes. PMID:26787866

  12. Intracellular compartmentation of ions in salt adapted tobacco cells. [Nicotiana tabacum L

    SciTech Connect

    Binzel, M.L.; Hess, F.D.; Bressan, R.A.; Hasegawa, P.M. )

    1988-02-01

    Na{sup +} and Cl{sup {minus}} are the principal solutes utilized for osmotic adjustment in cells of Nicotiana tabacum L. var Wisconsin 38 (tobacco) adapted to NaCl, accumulating to levels of 472 and 386 millimolar, respectively, in cells adapted to 428 millimolar NaCl. X-ray microanalysis of unetched frozen-hydrated cells adapted to salt indicated that Na{sup +} and Cl{sup {minus}} were compartmentalized in the vacuole, at concentrations of 780 and 624 millimolar, respectively, while cytoplasmic concentrations of the ions were maintained at 96 millimolar. The morphometric differences which existed between unadapted and salt adapted cells, (cytoplasmic volume of 22 and 45% of the cell, respectively), facilitated containment of the excited volume of the x-ray signal in the cytoplasm of the adapted cells. Confirmation of ion compartmentation in salt adapted cells was obtained based on kinetic analyses of {sup 22}Na{sup +} and {sup 36}Cl{sup {minus}} efflux from cells in steady state. These data provide evidence that ion compartmentation is a component of salt adaptation of glycophyte cells.

  13. The Peru Cervical Cancer Screening Study (PERCAPS): the design and implementation of a mother/daughter screen, treat, and vaccinate program in the Peruvian jungle.

    PubMed

    Abuelo, Carolina E; Levinson, Kimberly L; Salmeron, Jorge; Sologuren, Carlos Vallejos; Fernandez, Maria Jose Vallejos; Belinson, Jerome L

    2014-06-01

    Peru struggles to prevent cervical cancer (CC). In the jungle, prevention programs suffer from significant barriers although technology exists to detect CC precursors. This study used community based participatory research (CBPR) methods to overcome barriers. The objective was to evaluate the utility of CBPR techniques in a mother-child screen/treat and vaccinate program for CC prevention in the Peruvian jungle. The CC prevention program used self-sampling for human papillomavirus (HPV) for screening, cryotherapy for treatment and the HPV vaccine Gardasil for vaccination. Community health leaders (HL) from around Iquitos participated in a two half day educational course. The HLs then decided how to implement interventions in their villages or urban sectors. The success of the program was measured by: (1) ability of the HLs to determine an implementation plan, (2) proper use of research forms, (3) participation and retention rates, and (4) participants' satisfaction. HLs successfully registered 320 women at soup kitchens, schools, and health posts. Screening, treatment, and vaccination were successfully carried out using forms for registration, consent, and results with minimum error. In the screen/treat intervention 100% of participants gave an HPV sample and 99.7% reported high satisfaction; 81% of HPV + women were treated, and 57% returned for 6-month followup. Vaccine intervention: 98% of girls received the 1st vaccine, 88% of those received the 2nd, and 65% the 3rd. CBPR techniques successfully helped implement a screen/treat and vaccinate CC prevention program around Iquitos, Peru. These techniques may be appropriate for large-scale preventive health-care interventions.

  14. The Peru Cervical Cancer Screening Study (PERCAPS): The Design and Implementation of a Mother/Daughter Screen, Treat, and Vaccinate Program in the Peruvian Jungle

    PubMed Central

    Levinson, Kimberly L.; Salmeron, Jorge; Sologuren, Carlos Vallejos; Fernandez, Maria Jose Vallejos; Belinson, Jerome L.

    2014-01-01

    Peru struggles to prevent cervical cancer (CC). In the jungle, prevention programs suffer from significant barriers although technology exists to detect CC precursors. This study used community based participatory research (CBPR) methods to overcome barriers. The objective was to evaluate the utility of CBPR techniques in a mother–child screen/treat and vaccinate program for CC prevention in the Peruvian jungle. The CC prevention program used self-sampling for human papillomavirus (HPV) for screening, cryotherapy for treatment and the HPV vaccine Gardasil for vaccination. Community health leaders (HL) from around Iquitos participated in a two half day educational course. The HLs then decided how to implement interventions in their villages or urban sectors. The success of the program was measured by: (1) ability of the HLs to determine an implementation plan, (2) proper use of research forms, (3) participation and retention rates, and (4) participants’ satisfaction. HLs successfully registered 320 women at soup kitchens, schools, and health posts. Screening, treatment, and vaccination were successfully carried out using forms for registration, consent, and results with minimum error. In the screen/treat intervention 100 % of participants gave an HPV sample and 99.7 % reported high satisfaction; 81 % of HPV + women were treated, and 57 % returned for 6-month followup. Vaccine intervention: 98 % of girls received the 1st vaccine, 88 % of those received the 2nd, and 65 % the 3rd. CBPR techniques successfully helped implement a screen/treat and vaccinate CC prevention program around Iquitos, Peru. These techniques may be appropriate for large-scale preventive health-care interventions. PMID:24276617

  15. The Peru Cervical Cancer Screening Study (PERCAPS): the design and implementation of a mother/daughter screen, treat, and vaccinate program in the Peruvian jungle.

    PubMed

    Abuelo, Carolina E; Levinson, Kimberly L; Salmeron, Jorge; Sologuren, Carlos Vallejos; Fernandez, Maria Jose Vallejos; Belinson, Jerome L

    2014-06-01

    Peru struggles to prevent cervical cancer (CC). In the jungle, prevention programs suffer from significant barriers although technology exists to detect CC precursors. This study used community based participatory research (CBPR) methods to overcome barriers. The objective was to evaluate the utility of CBPR techniques in a mother-child screen/treat and vaccinate program for CC prevention in the Peruvian jungle. The CC prevention program used self-sampling for human papillomavirus (HPV) for screening, cryotherapy for treatment and the HPV vaccine Gardasil for vaccination. Community health leaders (HL) from around Iquitos participated in a two half day educational course. The HLs then decided how to implement interventions in their villages or urban sectors. The success of the program was measured by: (1) ability of the HLs to determine an implementation plan, (2) proper use of research forms, (3) participation and retention rates, and (4) participants' satisfaction. HLs successfully registered 320 women at soup kitchens, schools, and health posts. Screening, treatment, and vaccination were successfully carried out using forms for registration, consent, and results with minimum error. In the screen/treat intervention 100% of participants gave an HPV sample and 99.7% reported high satisfaction; 81% of HPV + women were treated, and 57% returned for 6-month followup. Vaccine intervention: 98% of girls received the 1st vaccine, 88% of those received the 2nd, and 65% the 3rd. CBPR techniques successfully helped implement a screen/treat and vaccinate CC prevention program around Iquitos, Peru. These techniques may be appropriate for large-scale preventive health-care interventions. PMID:24276617

  16. The Learning Theory Jungle

    ERIC Educational Resources Information Center

    Minter, Robert L.

    2011-01-01

    This article addresses the myriad of pedagogical and andragogical issues facing university educators in the student learning process. It briefly explores the proliferation of learning theories in an attempt to develop awareness among faculty who teach at the university/college levels that not all theories of learning apply to the adult learner. In…

  17. The Role of Nuclear Bodies in Gene Expression and Disease

    PubMed Central

    Morimoto, Marie; Boerkoel, Cornelius F.

    2013-01-01

    This review summarizes the current understanding of the role of nuclear bodies in regulating gene expression. The compartmentalization of cellular processes, such as ribosome biogenesis, RNA processing, cellular response to stress, transcription, modification and assembly of spliceosomal snRNPs, histone gene synthesis and nuclear RNA retention, has significant implications for gene regulation. These functional nuclear domains include the nucleolus, nuclear speckle, nuclear stress body, transcription factory, Cajal body, Gemini of Cajal body, histone locus body and paraspeckle. We herein review the roles of nuclear bodies in regulating gene expression and their relation to human health and disease. PMID:24040563

  18. Role of Compartmentalization on HiF-1α Degradation Dynamics during Changing Oxygen Conditions: A Computational Approach

    PubMed Central

    Bedessem, Baptiste; Stéphanou, Angélique

    2014-01-01

    HiF-1α is the central protein driving the cellular response to hypoxia. Its accumulation in cancer cells is linked to the appearance of chemoresistant and aggressive tumor phenotypes. As a consequence, understanding the regulation of HiF-1α dynamics is a major issue to design new anti-cancer therapies. In this paper, we propose a model of the hypoxia pathway, involving HiF-1α and its inhibitor pVHL. Based on data from the literature, we made the hypothesis that the regulation of HiF-1α involves two compartments (nucleus and cytoplasm) and a constitutive shuttle of the pVHL protein between them. We first show that this model captures correctly the main features of HiF-1α dynamics, including the bi-exponential degradation profile in normoxia, the kinetics of induction in hypoxia, and the switch-like accumulation. Second, we simulated the effects of a hypoxia/reoxygenation event, and show that it generates a strong instability of HiF-1α. The protein concentration rapidly increases 3 hours after the reoxygenation, and exhibits an oscillating pattern. This effect vanishes if we do not consider compartmentalization of HiF-1α. This result can explain various counter-intuitive observations about the specific molecular and cellular response to the reoxygenation process. Third, we simulated the HiF-1α dynamics in the tumor case. We considered different types of mutations associated with tumorigenesis, and we compared their consequences on HiF-1α dynamics. Then, we tested different therapeutics strategies. We show that a therapeutic decrease of HiF-1α nuclear level is not always correlated with an attenuation of reoxygenation-induced instabilities. Thus, it appears that the design of anti-HiF-1α therapies have to take into account these two aspects to maximize their efficiency. PMID:25338163

  19. Regulation of NAD+ metabolism, signaling and compartmentalization in the yeast Saccharomyces cerevisiae.

    PubMed

    Kato, Michiko; Lin, Su-Ju

    2014-11-01

    Pyridine nucleotides are essential coenzymes in many cellular redox reactions in all living systems. In addition to functioning as a redox carrier, NAD(+) is also a required co-substrate for the conserved sirtuin deacetylases. Sirtuins regulate transcription, genome maintenance and metabolism and function as molecular links between cells and their environment. Maintaining NAD(+) homeostasis is essential for proper cellular function and aberrant NAD(+) metabolism has been implicated in a number of metabolic- and age-associated diseases. Recently, NAD(+) metabolism has been linked to the phosphate-responsive signaling pathway (PHO pathway) in the budding yeast Saccharomyces cerevisiae. Activation of the PHO pathway is associated with the production and mobilization of the NAD(+) metabolite nicotinamide riboside (NR), which is mediated in part by PHO-regulated nucleotidases. Cross-regulation between NAD(+) metabolism and the PHO pathway has also been reported; however, detailed mechanisms remain to be elucidated. The PHO pathway also appears to modulate the activities of common downstream effectors of multiple nutrient-sensing pathways (Ras-PKA, TOR, Sch9/AKT). These signaling pathways were suggested to play a role in calorie restriction-mediated beneficial effects, which have also been linked to Sir2 function and NAD(+) metabolism. Here, we discuss the interactions of these pathways and their potential roles in regulating NAD(+) metabolism. In eukaryotic cells, intracellular compartmentalization facilitates the regulation of enzymatic functions and also concentrates or sequesters specific metabolites. Various NAD(+)-mediated cellular functions such as mitochondrial oxidative phosphorylation are compartmentalized. Therefore, we also discuss several key players functioning in mitochondrial, cytosolic and vacuolar compartmentalization of NAD(+) intermediates, and their potential roles in NAD(+) homeostasis. To date, it remains unclear how NAD(+) and NAD(+) intermediates

  20. Regulation of NAD+ metabolism, signaling and compartmentalization in the yeast Saccharomyces cerevisiae.

    PubMed

    Kato, Michiko; Lin, Su-Ju

    2014-11-01

    Pyridine nucleotides are essential coenzymes in many cellular redox reactions in all living systems. In addition to functioning as a redox carrier, NAD(+) is also a required co-substrate for the conserved sirtuin deacetylases. Sirtuins regulate transcription, genome maintenance and metabolism and function as molecular links between cells and their environment. Maintaining NAD(+) homeostasis is essential for proper cellular function and aberrant NAD(+) metabolism has been implicated in a number of metabolic- and age-associated diseases. Recently, NAD(+) metabolism has been linked to the phosphate-responsive signaling pathway (PHO pathway) in the budding yeast Saccharomyces cerevisiae. Activation of the PHO pathway is associated with the production and mobilization of the NAD(+) metabolite nicotinamide riboside (NR), which is mediated in part by PHO-regulated nucleotidases. Cross-regulation between NAD(+) metabolism and the PHO pathway has also been reported; however, detailed mechanisms remain to be elucidated. The PHO pathway also appears to modulate the activities of common downstream effectors of multiple nutrient-sensing pathways (Ras-PKA, TOR, Sch9/AKT). These signaling pathways were suggested to play a role in calorie restriction-mediated beneficial effects, which have also been linked to Sir2 function and NAD(+) metabolism. Here, we discuss the interactions of these pathways and their potential roles in regulating NAD(+) metabolism. In eukaryotic cells, intracellular compartmentalization facilitates the regulation of enzymatic functions and also concentrates or sequesters specific metabolites. Various NAD(+)-mediated cellular functions such as mitochondrial oxidative phosphorylation are compartmentalized. Therefore, we also discuss several key players functioning in mitochondrial, cytosolic and vacuolar compartmentalization of NAD(+) intermediates, and their potential roles in NAD(+) homeostasis. To date, it remains unclear how NAD(+) and NAD(+) intermediates

  1. Development and testing of a compartmentalized reaction network model for redox zones in contaminated aquifers

    USGS Publications Warehouse

    Abrams, R.H.; Loague, K.; Kent, D.B.

    1998-01-01

    The work reported here is the first part of a larger effort focused on efficient numerical simulation of redox zone development in contaminated aquifers. The sequential use of various electron acceptors, which is governed by the energy yield of each reaction, gives rise to redox zones. The large difference in energy yields between the various redox reactions leads to systems of equations that are extremely ill-conditioned. These equations are very difficult to solve, especially in the context of coupled fluid flow, solute transport, and geochemical simulations. We have developed a general, rational method to solve such systems where we focus on the dominant reactions, compartmentalizing them in a manner that is analogous to the redox zones that are often observed in the field. The compartmentalized approach allows us to easily solve a complex geochemical system as a function of time and energy yield, laying the foundation for our ongoing work in which we couple the reaction network, for the development of redox zones, to a model of subsurface fluid flow and solute transport. Our method (1) solves the numerical system without evoking a redox parameter, (2) improves the numerical stability of redox systems by choosing which compartment and thus which reaction network to use based upon the concentration ratios of key constituents, (3) simulates the development of redox zones as a function of time without the use of inhibition factors or switching functions, and (4) can reduce the number of transport equations that need to be solved in space and time. We show through the use of various model performance evaluation statistics that the appropriate compartment choice under different geochemical conditions leads to numerical solutions without significant error. The compartmentalized approach described here facilitates the next phase of this effort where we couple the redox zone reaction network to models of fluid flow and solute transport.

  2. In or out? On the tightness of glycosomal compartmentalization of metabolites and enzymes in Trypanosoma brucei.

    PubMed

    Haanstra, Jurgen R; Bakker, Barbara M; Michels, Paul A M

    2014-11-01

    Trypanosomatids sequester large parts of glucose metabolism inside specialised peroxisomes, called glycosomes. Many studies have shown that correct glycosomal compartmentalization of glycolytic enzymes is essential for bloodstream-form Trypanosoma brucei. The recent finding of pore-forming activities in glycosomal membrane preparations and extensions of the trypanosome glycolysis computer model with size-selective pores sparked again an old debate on the extent of (im)permeability of the glycosomal membrane and whether glycosomally located glycolytic enzymes could and should also be present with some activity in the cytosol. This review presents a critical discussion of the experimental and theoretical evidence for and against the different hypotheses. PMID:25476771

  3. Compartmentalized Cerebral Metabolism of [1,6-13C]Glucose Determined by in vivo 13C NMR Spectroscopy at 14.1 T

    PubMed Central

    Duarte, João M. N.; Lanz, Bernard; Gruetter, Rolf

    2011-01-01

    Cerebral metabolism is compartmentalized between neurons and glia. Although glial glycolysis is thought to largely sustain the energetic requirements of neurotransmission while oxidative metabolism takes place mainly in neurons, this hypothesis is matter of debate. The compartmentalization of cerebral metabolic fluxes can be determined by 13C nuclear magnetic resonance (NMR) spectroscopy upon infusion of 13C-enriched compounds, especially glucose. Rats under light α-chloralose anesthesia were infused with [1,6-13C]glucose and 13C enrichment in the brain metabolites was measured by 13C NMR spectroscopy with high sensitivity and spectral resolution at 14.1 T. This allowed determining 13C enrichment curves of amino acid carbons with high reproducibility and to reliably estimate cerebral metabolic fluxes (mean error of 8%). We further found that TCA cycle intermediates are not required for flux determination in mathematical models of brain metabolism. Neuronal tricarboxylic acid cycle rate (VTCA) and neurotransmission rate (VNT) were 0.45 ± 0.01 and 0.11 ± 0.01 μmol/g/min, respectively. Glial VTCA was found to be 38 ± 3% of total cerebral oxidative metabolism, accounting for more than half of neuronal oxidative metabolism. Furthermore, glial anaplerotic pyruvate carboxylation rate (VPC) was 0.069 ± 0.004 μmol/g/min, i.e., 25 ± 1% of the glial TCA cycle rate. These results support a role of glial cells as active partners of neurons during synaptic transmission beyond glycolytic metabolism. PMID:21713114

  4. A comparison of science achievement of fifth grade students in semi-departmentalized and compartmentalized instructional formats

    NASA Astrophysics Data System (ADS)

    Garcia, Gregorio

    The purpose of the proposed study was to examine the difference between semidepartmentalized instruction and compartmentalized instruction on the achievement of fifth grade students as measured by the Texas Assessment of Knowledge and Skills (TAKS) Fifth Grade Science test. The study utilized a Causal Comparative research design with six elementary schools that were comparable as defined by the Texas Education Agency. The independent variable was the type of organizational structure, semi-departmentalized instruction versus compartmentalized instruction. The dependent variable was the science achievement of fifth grade students as measured by the TAKS Fifth Grade Science test from spring 2004. A t-test for unpaired samples was used to analyze the data obtained from the semi-departmentalized group and the comparison group (compartmentalized). The ninety-five percent confidence level (p < 0.05) was used as the criterion level for determining statistical significance of the means. An effect size, Cohen's d, of 0.33 was used to determine educational significance between the means of the two groups. The results of the t-tests indicate that the semi-departmentalized schools had a mean scale score of 2026.52, while the compartmentalized schools had a mean scale score of 2041.22 that was not statistically significant ( p = .337). The effect size between the semi-departmentalized group and the compartmentalized comparison group yielded a Cohen's d = 0.08 that was not educationally significant.

  5. Detecting compartmental non-Gaussian diffusion with symmetrized double-PFG MRI.

    PubMed

    Paulsen, Jeffrey L; Özarslan, Evren; Komlosh, Michal E; Basser, Peter J; Song, Yi-Qiao

    2015-11-01

    Diffusion in tissue and porous media is known to be non-Gaussian and has been used for clinical indications of stroke and other tissue pathologies. However, when conventional NMR techniques are applied to biological tissues and other heterogeneous materials, the presence of multiple compartments (pores) with different Gaussian diffusivities will also contribute to the measurement of non-Gaussian behavior. Here we present symmetrized double PFG (sd-PFG), which can separate these two contributions to non-Gaussian signal decay as having distinct angular modulation frequencies. In contrast to prior angular d-PFG methods, sd-PFG can unambiguously extract kurtosis as an oscillation from samples with isotropic or uniformly oriented anisotropic pores, and can generally extract a combination of compartmental anisotropy and kurtosis. The method further fixes its sensitivity with respect to the time dependence of the apparent diffusion coefficient. We experimentally demonstrate the measurement of the fourth cumulant (kurtosis) of diffusion and find it consistent with theoretical predictions. By enabling the unambiguous identification of contributions of compartmental kurtosis to the signal, sd-PFG has the potential to help identify the underlying micro-structural changes corresponding to current kurtosis based diagnostics, and act as a novel source of contrast to better resolve tissue micro-structure.

  6. Metabolism of monoterpenes: evidence for compartmentation of l-menthone metabolism in peppermint (Mentha piperita) leaves

    SciTech Connect

    Martinkus, C.; Croteau, R.

    1981-01-01

    Previous studies have shown that the monoterpene ketone l-(G-/sup 3/H)-menthone is reduced to the epimeric alcohols l-menthol and d-neomenthol in leaf discs of flowering peppermint (Mentha piperita L.), and that a portion of the menthol is converted to menthyl acetate while the bulk of the neomenthol is transformed to neomenthyl-..beta..-D-glucoside. When l-(3-/sup 3/H)menthol and d-(3-/sup 3/H)neomenthol are separately administered to leaf discs, both menthyl and neomenthyl acetates and menthyl and neomenthyl glucosides are formed with nearly equal facility, suggesting that the metabolic specificity observed with the ketone precursor was not a function of the specificity of the transglucosylase or transacetylase but rather a result of compartmentation of each stereospecific dehydrogenase with the appropriate transferase. Co-purification of the acceptor-mediated activities, and differential activation and inhibition studies, provided strong evidence that the same UDP-glucose-dependent enzyme could transfer glucose to either l-menthol or d-neometnthol. These results demonstrate that the specific in vivo conversion of l-menthone to l-menthyl acetate and d-neomenthyl-..beta..-D-glucoside cannot be attributed to the selectivity of the transferases, and they clearly indicate that the metabolic specificity observed is a result of compartmentation effects.

  7. Modulation in Wistar Rats of Blood Corticosterone Compartmentation by Sex and a Cafeteria Diet

    PubMed Central

    Romero, María del Mar; Holmgren-Holm, Fredrik; Grasa, Maria del Mar; Esteve, Montserrat; Remesar, Xavier; Fernández-López, José Antonio; Alemany, Marià

    2013-01-01

    In the metabolic syndrome, glucocorticoid activity is increased, but circulating levels show little change. Most of blood glucocorticoids are bound to corticosteroid-binding globulin (CBG), which liver expression and circulating levels are higher in females than in males. Since blood hormones are also bound to blood cells, and the size of this compartment is considerable for androgens and estrogens, we analyzed whether sex or eating a cafeteria diet altered the compartmentation of corticosterone in rat blood. The main corticosterone compartment in rat blood is that specifically bound to plasma proteins, with smaller compartments bound to blood cells or free. Cafeteria diet increased the expression of liver CBG gene, binding plasma capacity and the proportion of blood cell-bound corticosterone. There were marked sex differences in blood corticosterone compartmentation in rats, which were unrelated to testosterone. The use of a monoclonal antibody ELISA and a polyclonal Western blot for plasma CBG compared with both specific plasma binding of corticosterone and CBG gene expression suggested the existence of different forms of CBG, with varying affinities for corticosterone in males and females, since ELISA data showed higher plasma CBG for males, but binding and Western blot analyses (plus liver gene expression) and higher physiological effectiveness for females. Good cross- reactivity to the antigen for polyclonal CBG antibody suggests that in all cases we were measuring CBG.The different immunoreactivity and binding affinity may help explain the marked sex-related differences in plasma hormone binding as sex-linked different proportions of CBG forms. PMID:23451210

  8. Detecting compartmental non-Gaussian diffusion with symmetrized double-PFG MRI.

    PubMed

    Paulsen, Jeffrey L; Özarslan, Evren; Komlosh, Michal E; Basser, Peter J; Song, Yi-Qiao

    2015-11-01

    Diffusion in tissue and porous media is known to be non-Gaussian and has been used for clinical indications of stroke and other tissue pathologies. However, when conventional NMR techniques are applied to biological tissues and other heterogeneous materials, the presence of multiple compartments (pores) with different Gaussian diffusivities will also contribute to the measurement of non-Gaussian behavior. Here we present symmetrized double PFG (sd-PFG), which can separate these two contributions to non-Gaussian signal decay as having distinct angular modulation frequencies. In contrast to prior angular d-PFG methods, sd-PFG can unambiguously extract kurtosis as an oscillation from samples with isotropic or uniformly oriented anisotropic pores, and can generally extract a combination of compartmental anisotropy and kurtosis. The method further fixes its sensitivity with respect to the time dependence of the apparent diffusion coefficient. We experimentally demonstrate the measurement of the fourth cumulant (kurtosis) of diffusion and find it consistent with theoretical predictions. By enabling the unambiguous identification of contributions of compartmental kurtosis to the signal, sd-PFG has the potential to help identify the underlying micro-structural changes corresponding to current kurtosis based diagnostics, and act as a novel source of contrast to better resolve tissue micro-structure. PMID:26434812

  9. Compartmentalized Fluid Flow In The Nevado Del Ruiz Volcano Hydrothermal System(S)

    NASA Astrophysics Data System (ADS)

    Zuluaga, C. A.; Mejia, E.

    2011-12-01

    Combination of several extensive and compressive fault/fracture systems with different lithologic units compartmentalized the hydrothermal system(s) in the vicinity of the Nevado del Ruiz volcano. Three main fault/fracture systems are observed in the Ruiz volcano area, a N10°-20°E system (San Jerónimo and Palestina faults), a N40°-60°W system (Villamaría-Termales, San Ramón, Nereidas, Río Claro, San Eugenio and Campoalegrito faults), and a N60°-80°E system (Santa Rosa fault). The NW trend system act as the main path for fluid circulation, location of faults and fractures belonging to this system and their intersections with other fault systems and/or with lithologic contacts control hot springs location. The observed fault location and hot spring location pattern allow to subdivide the hydrothermal system(s) in at least five blocks. In the southernmost block, hot springs are mostly located in one of the four quadrants originated by fault intersections suggesting that there is a compartmentalization into higher and lower permeability quadrants. It is still unknown if all blocks belong to the same hydrothermal system or if there is more than one hydrothermal system.

  10. Subcellular compartmentalization in protoplasts from Artemisia annua cell cultures: engineering attempts using a modified SNARE protein.

    PubMed

    Di Sansebastiano, Gian Pietro; Rizzello, Francesca; Durante, Miriana; Caretto, Sofia; Nisi, Rossella; De Paolis, Angelo; Faraco, Marianna; Montefusco, Anna; Piro, Gabriella; Mita, Giovanni

    2015-05-20

    Plants are ideal bioreactors for the production of macromolecules but transport mechanisms are not fully understood and cannot be easily manipulated. Several attempts to overproduce recombinant proteins or secondary metabolites failed. Because of an independent regulation of the storage compartment, the product may be rapidly degraded or cause self-intoxication. The case of the anti-malarial compound artemisinin produced by Artemisia annua plants is emblematic. The accumulation of artemisinin naturally occurs in the apoplast of glandular trichomes probably involving autophagy and unconventional secretion thus its production by undifferentiated tissues such as cell suspension cultures can be challenging. Here we characterize the subcellular compartmentalization of several known fluorescent markers in protoplasts derived from Artemisia suspension cultures and explore the possibility to modify compartmentalization using a modified SNARE protein as molecular tool to be used in future biotechnological applications. We focused on the observation of the vacuolar organization in vivo and the truncated form of AtSYP51, 51H3, was used to induce a compartment generated by the contribution of membrane from endocytosis and from endoplasmic reticulum to vacuole trafficking. The artificial compartment crossing exocytosis and endocytosis may trap artemisinin stabilizing it until extraction; indeed, it is able to increase total enzymatic activity of a vacuolar marker (RGUSChi), probably increasing its stability. Exploring the 51H3-induced compartment we gained new insights on the function of the SNARE SYP51, recently shown to be an interfering-SNARE, and new hints to engineer eukaryote endomembranes for future biotechnological applications.

  11. Vacuolar compartmentalization as indispensable component of heavy metal detoxification in plants.

    PubMed

    Sharma, Shanti S; Dietz, Karl-Josef; Mimura, Tetsuro

    2016-05-01

    Plant cells orchestrate an array of molecular mechanisms for maintaining plasmatic concentrations of essential heavy metal (HM) ions, for example, iron, zinc and copper, within the optimal functional range. In parallel, concentrations of non-essential HMs and metalloids, for example, cadmium, mercury and arsenic, should be kept below their toxicity threshold levels. Vacuolar compartmentalization is central to HM homeostasis. It depends on two vacuolar pumps (V-ATPase and V-PPase) and a set of tonoplast transporters, which are directly driven by proton motive force, and primary ATP-dependent pumps. While HM non-hyperaccumulator plants largely sequester toxic HMs in root vacuoles, HM hyperaccumulators usually sequester them in leaf cell vacuoles following efficient long-distance translocation. The distinct strategies evolved as a consequence of organ-specific differences particularly in vacuolar transporters and in addition to distinct features in long-distance transport. Recent molecular and functional characterization of tonoplast HM transporters has advanced our understanding of their contribution to HM homeostasis, tolerance and hyperaccumulation. Another important part of the dynamic vacuolar sequestration syndrome involves enhanced vacuolation. It involves vesicular trafficking in HM detoxification. The present review provides an updated account of molecular aspects that contribute to the vacuolar compartmentalization of HMs. PMID:26729300

  12. Intracellular Redox Compartmentation and ROS-Related Communication in Regulation and Signaling.

    PubMed

    Noctor, Graham; Foyer, Christine H

    2016-07-01

    Recent years have witnessed enormous progress in understanding redox signaling related to reactive oxygen species (ROS) in plants. The consensus view is that such signaling is intrinsic to many developmental processes and responses to the environment. ROS-related redox signaling is tightly wedded to compartmentation. Because membranes function as barriers, highly redox-active powerhouses such as chloroplasts, peroxisomes, and mitochondria may elicit specific signaling responses. However, transporter functions allow membranes also to act as bridges between compartments, and so regulated capacity to transmit redox changes across membranes influences the outcome of triggers produced at different locations. As well as ROS and other oxidizing species, antioxidants are key players that determine the extent of ROS accumulation at different sites and that may themselves act as signal transmitters. Like ROS, antioxidants can be transported across membranes. In addition, the intracellular distribution of antioxidative enzymes may be modulated to regulate or facilitate redox signaling appropriate to the conditions. Finally, there is substantial plasticity in organellar shape, with extensions such as stromules, peroxules, and matrixules playing potentially crucial roles in organelle-organelle communication. We provide an overview of the advances in subcellular compartmentation, identifying the gaps in our knowledge and discussing future developments in the area. PMID:27208308

  13. Structure of the Archaeal Pab87 Peptidase Reveals a Novel Self-Compartmentalizing Protease Family

    PubMed Central

    Delfosse, Vanessa; Girard, Eric; Birck, Catherine; Delmarcelle, Michaël; Delarue, Marc; Poch, Olivier; Schultz, Patrick; Mayer, Claudine

    2009-01-01

    Self-compartmentalizing proteases orchestrate protein turnover through an original architecture characterized by a central catalytic chamber. Here we report the first structure of an archaeal member of a new self-compartmentalizing protease family forming a cubic-shaped octamer with D4 symmetry and referred to as CubicO. We solved the structure of the Pyrococcus abyssi Pab87 protein at 2.2 Å resolution using the anomalous signal of the high-phasing-power lanthanide derivative Lu-HPDO3A. A 20 Å wide channel runs through this supramolecular assembly of 0.4 MDa, giving access to a 60 Å wide central chamber holding the eight active sites. Surprisingly, activity assays revealed that Pab87 degrades specifically d-amino acid containing peptides, which have never been observed in archaea. Genomic context of the Pab87 gene showed that it is surrounded by genes involved in the amino acid/peptide transport or metabolism. We propose that CubicO proteases are involved in the processing of d-peptides from environmental origins. PMID:19266066

  14. Estimation of guinea pig tracheobronchial transport rates using a compartmental model

    SciTech Connect

    Velasquez, D.J.; Morrow, P.E.

    1984-01-01

    Mucociliary clearance in the tracheobronchial tree of guinea pigs was examined using monodisperse 7.9 ..mu..m MMAD polystyrene particles. Animals were exposed for approximately 1 h by inhalation via an intratracheal tube to aerosols tagged with gold-198 and fluorescent dyes. Following exposure, animals were radioactively monitored and sacrificed at predetermined times. The lungs were removed, freeze-dried, sectioned completely, and examined with a fluorescent microscope. Measurements were made of airway diameters where particles were found. An anatomic model for guinea pig lung morphology was used to assign ranges of airway diameters to five zones, which were incorporated into a compartmental model for lung clearance. Kinetic analysis of particle distributions in the zones led to development of first-order equations describing the compartmental clearance. Rate constants obtained from the kinetic analysis were used to estimate mucociliary transport rates in specific bronchial generations, which ranged from approximately 0.001 mm/min in the distal bronchioles to approximately 8 mm/min in the trachea, and resulted in a calculated 24-h clearance time for tracheobronchial clearance in the guinea pig. No evidence for either bronchial penetration by particles or relatively prolonged bronchial retention of particles was found in this study. 22 references, 3 figures, 3 tables.

  15. Intracellular Redox Compartmentation and ROS-Related Communication in Regulation and Signaling1[OPEN

    PubMed Central

    2016-01-01

    Recent years have witnessed enormous progress in understanding redox signaling related to reactive oxygen species (ROS) in plants. The consensus view is that such signaling is intrinsic to many developmental processes and responses to the environment. ROS-related redox signaling is tightly wedded to compartmentation. Because membranes function as barriers, highly redox-active powerhouses such as chloroplasts, peroxisomes, and mitochondria may elicit specific signaling responses. However, transporter functions allow membranes also to act as bridges between compartments, and so regulated capacity to transmit redox changes across membranes influences the outcome of triggers produced at different locations. As well as ROS and other oxidizing species, antioxidants are key players that determine the extent of ROS accumulation at different sites and that may themselves act as signal transmitters. Like ROS, antioxidants can be transported across membranes. In addition, the intracellular distribution of antioxidative enzymes may be modulated to regulate or facilitate redox signaling appropriate to the conditions. Finally, there is substantial plasticity in organellar shape, with extensions such as stromules, peroxules, and matrixules playing potentially crucial roles in organelle-organelle communication. We provide an overview of the advances in subcellular compartmentation, identifying the gaps in our knowledge and discussing future developments in the area. PMID:27208308

  16. Recovery of fish communities in the Finniss River, northern Australia, following remediation of the Rum Jungle uranium/copper mine site.

    PubMed

    Jeffree, R A; Twining, J R; Thomson, J

    2001-07-15

    The Finniss River in the wet-dry tropics of northern Australia has received acid rock drainage (ARD) contaminants from the Rum Jungle uranium/copper mine site over more than four decades. Annual-cycle loads of Cu, Zn, Mn, and sulfate, calculated from daily water and flow measurements, have been determined both prior to and following mine-site remediation, that began in the early 1980s. The effects of varying contaminant loads on the relative abundances of seven fish species, sampled by enmeshing nets during dry seasons, were determined by nonmetric multidimensional scaling (nMDS), in combination with cluster-analysis and other nonparametric statistical techniques. These analyses showed that (i) prior to remediation, the impacted region of the Finniss River in 1974 had significantly dissimilar (P < 0.001) and more heterogeneous fish communities, generally characterized by reduced diversity and abundance, compared to sites unexposed to elevated contaminant water concentrations and (ii) postremediation, recovery in fish communities from the impacted region was indicated because they were not significantly dissimilar from those sampled at contemporary (P = 0.16) unimpacted sites, that were also similar to preremedial unimpacted sites. Even though considerable contaminant loads are still being delivered to the impacted region of the Finniss River over the annual cycle, the recovery in fish diversity and abundances is consistent with (a) reductions of in situ contaminant water concentrations at the time of fish sampling, (b) reductions in annual-cycle contaminant loads of sulfate, Cu, Zn, and Mn by factors of 3-7, (c) greatly reduced frequencies of occurrence and magnitude of elevated contaminant water concentrations over the annual cycle, that was most pronounced for Cu, and (d) the absence of extensive fish-kills during the first-flushes of contaminants into the Finniss river proper at the beginning of the wet season, that were observed prior to remediation. As such

  17. Two-step adsorption on jungle-gym-type porous coordination polymers: dependence on hydrogen-bonding capability of adsorbates, ligand-substituent effect, and temperature.

    PubMed

    Uemura, Kazuhiro; Yamasaki, Yukari; Onishi, Fumiaki; Kita, Hidetoshi; Ebihara, Masahiro

    2010-11-01

    A preliminary study of isopropanol (IPA) adsorption/desorption isotherms on a jungle-gym-type porous coordination polymer, [Zn(2)(bdc)(2)(dabco)](n) (1, H(2)bdc = 1,4-benzenedicarboxylic acid, dabco =1,4-diazabicyclo[2.2.2]octane), showed unambiguous two-step profiles via a highly shrunk intermediate framework. The results of adsorption measurements on 1, using probing gas molecules of alcohol (MeOH and EtOH) for the size effect and Me(2)CO for the influence of hydrogen bonding, show that alcohol adsorption isotherms are gradual two-step profiles, whereas the Me(2)CO isotherm is a typical type-I isotherm, indicating that a two-step adsorption/desorption is involved with hydrogen bonds. To further clarify these characteristic adsorption/desorption behaviors, selecting nitroterephthalate (bdc-NO(2)), bromoterephthalate (bdc-Br), and 2,5-dichloroterephthalate (bdc-Cl(2)) as substituted dicarboxylate ligands, isomorphous jungle-gym-type porous coordination polymers, {[Zn(2)(bdc-NO(2))(2)(dabco)]·solvents}(n) (2 ⊃ solvents), {[Zn(2)(bdc-Br)(2)(dabco)]·solvents}(n) (3 ⊃ solvents), and {[Zn(2)(bdc-Cl(2))(2)(dabco)]·solvents}(n) (4 ⊃ solvents), were synthesized and characterized by single-crystal X-ray analyses. Thermal gravimetry, X-ray powder diffraction, and N(2) adsorption at 77 K measurements reveal that [Zn(2)(bdc-NO(2))(2)(dabco)](n) (2), [Zn(2)(bdc-Br)(2)(dabco)](n) (3), and [Zn(2)(bdc-Cl(2))(2)(dabco)](n) (4) maintain their frameworks without guest molecules with Brunauer-Emmett-Teller (BET) surface areas of 1568 (2), 1292 (3), and 1216 (4) m(2) g(-1). As found in results of MeOH, EtOH, IPA, and Me(2)CO adsorption/desorption on 2-4, only MeOH adsorption on 2 shows an obvious two-step profile. Considering the substituent effects and adsorbate sizes, the hydrogen bonds, which are triggers for two-step adsorption, are formed between adsorbates and carboxylate groups at the corners in the pores, inducing wide pores to become narrow pores. Interestingly, such

  18. Compartmentalized PDE4A5 Signaling Impairs Hippocampal Synaptic Plasticity and Long-Term Memory

    PubMed Central

    Park, Alan J.; Tolentino, Rosa E.; Bruinenberg, Vibeke M.; Tudor, Jennifer C.; Lee, Yool; Hansen, Rolf T.; Guercio, Leonardo A.; Linton, Edward; Neves-Zaph, Susana R.; Meerlo, Peter; Baillie, George S.; Houslay, Miles D.

    2016-01-01

    Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo. Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling. SIGNIFICANCE STATEMENT Neurons exhibit localized signaling processes that enable biochemical cascades to be activated selectively in specific subcellular

  19. Differential interhemispheric cooling and ICP compartmentalization in a patient with left ICA occlusion.

    PubMed

    Wang, H; Wang, D; Lanzino, G; Elkins, W; Olivero, W

    2006-06-01

    We report a case of a 69-year-old white female who presented with a large left internal carotid artery occlusive stroke from a cardiogenic embolus. She was enrolled in an institutional study using a specially designed cooling helmet. Bilateral intracranial pressure (ICP) and temperature probes were placed to determine if there was any differential cooling and ICP compartmentalization between the two hemispheres. We demonstrated a significant temperature gradient between the infarcted and the non-infarcted hemisphere. A significant inter-hemispheric ICP gradient was also observed. We believe that this is the first demonstration of preferential cooling of the infarcted hemisphere over the non-infarcted hemisphere with regional surface hypothermia. PMID:16502336

  20. Information Processing in Single Cells and Small Networks: Insights from Compartmental Models

    NASA Astrophysics Data System (ADS)

    Poirazi, Panayiota

    2009-03-01

    The goal of this paper is to present a set of predictions generated by detailed compartmental models regarding the ways in which information may be processed, encoded and propagated by single cells and neural assemblies. Towards this goal, I will review a number of modelling studies from our lab that investigate how single pyramidal neurons and small neural networks in different brain regions process incoming signals that are associated with learning and memory. I will first discuss the computational capabilities of individual pyramidal neurons in the hippocampus [1-3] and how these properties may allow a single cell to discriminate between different memories [4]. I will then present biophysical models of prefrontal layer V neurons and small networks that exhibit sustained activity under realistic synaptic stimulation and discuss their potential role in working memory [5].

  1. Compartmentalization of metabolic pathways in yeast mitochondria improves production of branched chain alcohols

    PubMed Central

    Avalos, José L.; Fink, Gerald R.; Stephanopoulos, Gregory

    2013-01-01

    Efforts to improve the production of a compound of interest in Saccharomyces cerevisiae have mainly involved engineering or overexpression of cytoplasmic enzymes. We show that targeted expression of metabolic pathways to mitochondria can increase production levels compared with expression of the same pathways in the cytoplasm. Compartmentalisation of the Ehrlich pathway into mitochondria increased isobutanol production by 260%, whereas overexpression of the same pathway in the cytoplasm only improved yields by 10%, compared with a strain overexpressing only the first three steps of the biosynthetic pathway. Subcellular fractionation of engineered strains reveals that targeting the enzymes of the Ehrlich pathway to the mitochondria achieves higher local enzyme concentrations. Other benefits of compartmentalization may include increased availability of intermediates, removing the need to transport intermediates out of the mitochondrion, and reducing the loss of intermediates to competing pathways. PMID:23417095

  2. Quantitation of renal function based on two-compartmental modeling of renal pelvis.

    PubMed

    Kah Meng, Loh; Ng, David; Ghista, Dhanjoo; Rudolph, Heiko

    2005-01-01

    The primary functions of the kidney are: (i) to get rid of the body waste materials that are either ingested or produced by metabolism, and (ii) to control the volume and composition of the body fluids. Herein, we provide a noninvasive methodology to assess physiological function of the kidneys. For this purpose, we analyze the renograms with 2-compartmental modelling of the kidney-renal outflow system, and therefrom compute the amount of flow of renal radionuclide into and out of the renal pelvis compartment. The derived information of uptake (k/A) and washout (e(beta/2V2)t sinhAt) rates can be of considerable use. The paper provides a number of case studies for the verification of the derived system governing equations against clinical renograms.

  3. Compartmentalization, Viral Evolution, and Viral Latency of HIV in the CNS.

    PubMed

    Bednar, Maria M; Sturdevant, Christa Buckheit; Tompkins, Lauren A; Arrildt, Kathryn Twigg; Dukhovlinova, Elena; Kincer, Laura P; Swanstrom, Ronald

    2015-06-01

    Human immunodeficiency virus type 1 (HIV-1) infection occurs throughout the body and can have dramatic physical effects, such as neurocognitive impairment in the central nervous system (CNS). Furthermore, examining the virus that resides in the CNS is challenging due to its location and can only be done using samples collected either at autopsy, indirectly form the cerebral spinal fluid (CSF), or through the use of animal models. The unique milieu of the CNS fosters viral compartmentalization as well as evolution of viral sequences, allowing for new cell types, such as macrophages and microglia, to be infected. Treatment must also cross the blood-brain barrier adding additional obstacles in eliminating viral populations in the CNS. These long-lived infected cell types and treatment barriers may affect functional cure strategies in people on highly active antiretroviral therapy (HAART). PMID:25914150

  4. Ultrasensitive quantification of TAP-dependent antigen compartmentalization in scarce primary immune cell subsets.

    PubMed

    Fischbach, Hanna; Döring, Marius; Nikles, Daphne; Lehnert, Elisa; Baldauf, Christoph; Kalinke, Ulrich; Tampé, Robert

    2015-01-01

    Presentation of peptides on major histocompatibility complex class I (MHC I) is essential for the establishment and maintenance of self-tolerance, priming of antigen-specific CD8(+) T cells and the exertion of several T-cell effector functions. Cytosolic proteasomes continuously degrade proteins into peptides, which are actively transported across the endoplasmic reticulum (ER) membrane by the transporter associated with antigen processing (TAP). In the ER lumen antigenic peptides are loaded onto MHC I, which is displayed on the cell surface. Here we describe an innovative flow cytometric approach to monitor time-resolved ER compartmentalization of antigenic peptides. This assay allows the analysis of distinct primary human immune cell subsets at reporter peptide concentrations of 1 nM. Thus, this ultrasensitive method for the first time permits quantification of TAP activity under close to physiological conditions in scarce primary cell subsets such as antigen cross-presenting dendritic cells. PMID:25656091

  5. The planar cell polarity protein Vangl2 is involved in postsynaptic compartmentalization.

    PubMed

    Nagaoka, Tadahiro; Kishi, Masashi

    2016-01-26

    The excitatory postsynaptic region of the vertebrate hippocampus is usually compartmentalized into the postsynaptic density (PSD) and N-cadherin-rich domain, which is important for synaptic adhesion. However, the molecular mechanisms underlying the compartment formation are unknown. In the present report, we show that the planar cell polarity (PCP) protein Van Gogh-like 2 (Vangl2) plays a role in this regionalization. In cultured rat hippocampal neurons that were subjected to Vangl2 expression silencing, the formed clusters of PSD-95, one of the major scaffolding proteins in PSD, tended to overlap with those of N-cadherin. Further, in the dendrites of these neurons, the immunofluorescence of PSD-95 was to some extent diffused, without a significant change in the total signal. Because Vangl2 physically interacts with both PSD-95 and N-cadherin in vivo, these results suggest that a PCP-related direct molecular mechanism underlies the horizontal polarization of the postsynaptic regions. PMID:26683906

  6. Spatial Compartmentalization Specializes the Function of Aurora A and Aurora B*

    PubMed Central

    Li, Si; Deng, Zhaoxuan; Fu, Jingyan; Xu, Caiyue; Xin, Guangwei; Wu, Zhige; Luo, Jia; Wang, Gang; Zhang, Shuli; Zhang, Boyan; Zou, Fangdong; Jiang, Qing; Zhang, Chuanmao

    2015-01-01

    Aurora kinase A and B share great similarity in sequences, structures, and phosphorylation motif, yet they show different localizations and play distinct crucial roles. The factors that determine such differences are largely unknown. Here we targeted Aurora A to the localization of Aurora B and found that Aurora A phosphorylates the substrate of Aurora B and substitutes its function in spindle checkpoint. In return, the centrosome targeting of Aurora B substitutes the function of Aurora A in the mitotic entry. Expressing the chimera proteins of the Auroras with exchanged N termini in cells indicates that the divergent N termini are also important for their spatiotemporal localizations and functions. Collectively, we demonstrate that functional divergence of Aurora kinases is determined by spatial compartmentalization, and their divergent N termini also contribute to their spatial and functional differentiation. PMID:25987563

  7. Compartmentalization of gypsum and halite associated with cyanobacteria in saline soil crusts.

    PubMed

    Canfora, Loredana; Vendramin, Elisa; Vittori Antisari, Livia; Lo Papa, Giuseppe; Dazzi, Carmelo; Benedetti, Anna; Iavazzo, Pietro; Adamo, Paola; Jungblut, Anne D; Pinzari, Flavia

    2016-06-01

    The interface between biological and geochemical components in the surface crust of a saline soil was investigated using X-ray diffraction, and variable pressure scanning electron microscopy in combination with energy dispersive X-ray spectrometry. Mineral compounds such as halite and gypsum were identified crystallized around filaments of cyanobacteria. A total of 92 genera were identified from the bacterial community based on 16S gene pyrosequencing analysis. The occurrence of the gypsum crystals, their shapes and compartmentalization suggested that they separated NaCl from the immediate microenvironment of the cyanobacteria, and that some cyanobacteria and communities of sulfur bacteria may had a physical control over the distinctive halite and gypsum structures produced. This suggests that cyanobacteria might directly or indirectly promote the formation of a protective envelope made of calcium and sulfur-based compounds. PMID:27090760

  8. Membrane Compartmentalization Reducing the Mobility of Lipids and Proteins within a Model Plasma Membrane.

    PubMed

    Koldsø, Heidi; Reddy, Tyler; Fowler, Philip W; Duncan, Anna L; Sansom, Mark S P

    2016-09-01

    The cytoskeleton underlying cell membranes may influence the dynamic organization of proteins and lipids within the bilayer by immobilizing certain transmembrane (TM) proteins and forming corrals within the membrane. Here, we present coarse-grained resolution simulations of a biologically realistic membrane model of asymmetrically organized lipids and TM proteins. We determine the effects of a model of cytoskeletal immobilization of selected membrane proteins using long time scale coarse-grained molecular dynamics simulations. By introducing compartments with varying degrees of restraints within the membrane models, we are able to reveal how compartmentalization caused by cytoskeletal immobilization leads to reduced and anomalous diffusional mobility of both proteins and lipids. This in turn results in a reduced rate of protein dimerization within the membrane and of hopping of membrane proteins between compartments. These simulations provide a molecular realization of hierarchical models often invoked to explain single-molecule imaging studies of membrane proteins.

  9. Spatial Compartmentalization Specializes the Function of Aurora A and Aurora B.

    PubMed

    Li, Si; Deng, Zhaoxuan; Fu, Jingyan; Xu, Caiyue; Xin, Guangwei; Wu, Zhige; Luo, Jia; Wang, Gang; Zhang, Shuli; Zhang, Boyan; Zou, Fangdong; Jiang, Qing; Zhang, Chuanmao

    2015-07-10

    Aurora kinase A and B share great similarity in sequences, structures, and phosphorylation motif, yet they show different localizations and play distinct crucial roles. The factors that determine such differences are largely unknown. Here we targeted Aurora A to the localization of Aurora B and found that Aurora A phosphorylates the substrate of Aurora B and substitutes its function in spindle checkpoint. In return, the centrosome targeting of Aurora B substitutes the function of Aurora A in the mitotic entry. Expressing the chimera proteins of the Auroras with exchanged N termini in cells indicates that the divergent N termini are also important for their spatiotemporal localizations and functions. Collectively, we demonstrate that functional divergence of Aurora kinases is determined by spatial compartmentalization, and their divergent N termini also contribute to their spatial and functional differentiation. PMID:25987563

  10. Ultrasensitive quantification of TAP-dependent antigen compartmentalization in scarce primary immune cell subsets

    PubMed Central

    Fischbach, Hanna; Döring, Marius; Nikles, Daphne; Lehnert, Elisa; Baldauf, Christoph; Kalinke, Ulrich; Tampé, Robert

    2015-01-01

    Presentation of peptides on major histocompatibility complex class I (MHC I) is essential for the establishment and maintenance of self-tolerance, priming of antigen-specific CD8+ T cells and the exertion of several T-cell effector functions. Cytosolic proteasomes continuously degrade proteins into peptides, which are actively transported across the endoplasmic reticulum (ER) membrane by the transporter associated with antigen processing (TAP). In the ER lumen antigenic peptides are loaded onto MHC I, which is displayed on the cell surface. Here we describe an innovative flow cytometric approach to monitor time-resolved ER compartmentalization of antigenic peptides. This assay allows the analysis of distinct primary human immune cell subsets at reporter peptide concentrations of 1 nM. Thus, this ultrasensitive method for the first time permits quantification of TAP activity under close to physiological conditions in scarce primary cell subsets such as antigen cross-presenting dendritic cells. PMID:25656091

  11. Further studies on the nature of fluid compartmentalization in chick calvaria.

    PubMed

    Neuman, W F; Bareham, B J

    1975-06-01

    Labeled mannitol and polyethylene glycol (mol. wt. 4000), PEG, were used as space markers to estimate the fluid compartmentalization of calvaria taken from 3-5-day-old chicks. The mannitol results indicated that about 80% of the water in these bones is extracellular. Only a small fraction of this extracellular space was available to the diffusion of polyehtylene glycol. Adsorption studies in vitro and prior incubation of the tissues with hydrolytic enzymes indicated that the phenomenon of exclusion of PEG was primarily physical in nature. The polyethylene polymer is excluded from the water of hydration of the mineral phase. Apparently much of the extracellular water (two-thirds) of bone is in the form of crystal hydration.

  12. Spatial Compartmentalization Specializes the Function of Aurora A and Aurora B.

    PubMed

    Li, Si; Deng, Zhaoxuan; Fu, Jingyan; Xu, Caiyue; Xin, Guangwei; Wu, Zhige; Luo, Jia; Wang, Gang; Zhang, Shuli; Zhang, Boyan; Zou, Fangdong; Jiang, Qing; Zhang, Chuanmao

    2015-07-10

    Aurora kinase A and B share great similarity in sequences, structures, and phosphorylation motif, yet they show different localizations and play distinct crucial roles. The factors that determine such differences are largely unknown. Here we targeted Aurora A to the localization of Aurora B and found that Aurora A phosphorylates the substrate of Aurora B and substitutes its function in spindle checkpoint. In return, the centrosome targeting of Aurora B substitutes the function of Aurora A in the mitotic entry. Expressing the chimera proteins of the Auroras with exchanged N termini in cells indicates that the divergent N termini are also important for their spatiotemporal localizations and functions. Collectively, we demonstrate that functional divergence of Aurora kinases is determined by spatial compartmentalization, and their divergent N termini also contribute to their spatial and functional differentiation.

  13. Engineering of customized meganucleases via in vitro compartmentalization and in cellulo optimization

    PubMed Central

    Takeuchi, Ryo; Choi, Michael; Stoddard, Barry L.

    2015-01-01

    Summary LAGLIDADG homing endonucleases (also referred to as ‘meganucleases’) are compact DNA cleaving enzymes that specifically recognize long target sequences (approximately 20 base pairs), and thus serve as useful tools for therapeutic genome engineering. While stand-alone meganucleases are sufficiently active to introduce targeted genome modification, they can be fused to additional sequence-specific DNA binding domains in order to improve their performance in target cells. In this chapter, we describe an approach to retarget meganucleases to DNA targets of interest (such as sequences found in genes and cis regulatory regions), which is feasible in an academic laboratory environment. A combination of two selection systems, in vitro compartmentalization and two-plasmid cleavage assay in bacteria, allow for efficient engineering of meganucleases that specifically cleave a wide variety of DNA sequences. PMID:25408403

  14. Cerebrospinal fluid HIV-1 compartmentalization in a patient with AIDS and acute varicella-zoster virus meningomyeloradiculitis.

    PubMed

    Falcone, E Liana; Adegbulugbe, Ademiposi A; Sheikh, Virginia; Imamichi, Hiromi; Dewar, Robin L; Hammoud, Dima A; Sereti, Irini; Lane, H Clifford

    2013-09-01

    We report a case of AIDS presenting as varicella-zoster virus (VZV) meningomyeloradiculitis associated with human immunodeficiency virus (HIV) quasispecies compartmentalization within the cerebrospinal fluid (CSF), and a CSF viral load that was 1 log higher than in peripheral blood. Prolonged antiviral therapy for both VZV and HIV type 1 was associated with partial resolution.

  15. Lipid droplet-associated proteins (LDAPs) are required for the dynamic regulation of neutral lipid compartmentation in plant cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eukaryotic cells compartmentalize neutral lipids into organelles called lipid droplets (LDs), and while much is known about the role of LDs in storing triacylglycerols (TAGs) in seeds, their biogenesis and function in non-seed tissues is poorly understood. Recently, we identified a class of plant-sp...

  16. Sequence Stratigraphy of the Dakota Sandstone, Eastern San Juan Basin, New Mexico, and its Relationship to Reservoir Compartmentalization

    SciTech Connect

    Varney, Peter J.

    2002-04-23

    This research established the Dakota-outcrop sequence stratigraphy in part of the eastern San Juan Basin, New Mexico, and relates reservoir quality lithologies in depositional sequences to structure and reservoir compartmentalization in the South Lindrith Field area. The result was a predictive tool that will help guide further exploration and development.

  17. Cellular compartmentation of cadmium and zinc in relation to other elements in the hyperaccumulator Arabidopsis halleri.

    PubMed

    Küpper, H; Lombi, E; Zhao, F J; McGrath, S P

    2000-12-01

    The cellular compartmentation of elements was analysed in the Zn hyperaccumulator Arabidopsis halleri (L.) O'Kane & Al-Shehbaz (=Cardaminopsis halleri) using energy-dispersive X-ray microanalysis of frozen-hydrated tissues. Quantitative data were obtained using oxygen as an internal standard in the analyses of vacuoles, whereas a peak/background ratio method was used for quantification of elements in pollen and dehydrated trichomes. Arabidopsis halleri was found to hyperaccumulate not only Zn but also Cd in the shoot biomass. While large concentrations of Zn and Cd were found in the leaves and roots, flowers contained very little. In roots grown hydroponically, Zn and Cd accumulated in the cell wall of the rhizodermis (root epidermis), mainly due to precipitation of Zn/Cd phosphates. In leaves, the trichomes had by far the largest concentrations of Zn and Cd. Inside the trichomes there was a striking sub-cellular compartmentation, with almost all the Zn and Cd being accumulated in a narrow ring in the trichome base. This distribution pattern was very different from that for Ca and P. The epidermal cells other than trichomes were very small and contained lower concentrations of Zn and Cd than mesophyll cells. In particular, the concentrations of Cd and Zn in the mesophyll cells increased markedly in response to increasing Zn and Cd concentrations in the nutrient solution. This indicates that the mesophyll cells in the leaves of A. halleri are the major storage site for Zn and Cd, and play an important role in their hyperaccumulation. PMID:11219586

  18. The role of the bi-compartmental stem cell niche in delaying cancer

    NASA Astrophysics Data System (ADS)

    Shahriyari, Leili; Komarova, Natalia L.

    2015-10-01

    In recent years, by using modern imaging techniques, scientists have found evidence of collaboration between different types of stem cells (SCs), and proposed a bi-compartmental organization of the SC niche. Here we create a class of stochastic models to simulate the dynamics of such a heterogeneous SC niche. We consider two SC groups: the border compartment, S1, is in direct contact with transit-amplifying (TA) cells, and the central compartment, S2, is hierarchically upstream from S1. The S1 SCs differentiate or divide asymmetrically when the tissue needs TA cells. Both groups proliferate when the tissue requires SCs (thus maintaining homeostasis). There is an influx of S2 cells into the border compartment, either by migration, or by proliferation. We examine this model in the context of double-hit mutant generation, which is a rate-limiting step in the development of many cancers. We discover that this type of a cooperative pattern in the stem niche with two compartments leads to a significantly smaller rate of double-hit mutant production compared with a homogeneous, one-compartmental SC niche. Furthermore, the minimum probability of double-hit mutant generation corresponds to purely symmetric division of SCs, consistent with the literature. Finally, the optimal architecture (which minimizes the rate of double-hit mutant production) requires a large proliferation rate of S1 cells along with a small, but non-zero, proliferation rate of S2 cells. This result is remarkably similar to the niche structure described recently by several authors, where one of the two SC compartments was found more actively engaged in tissue homeostasis and turnover, while the other was characterized by higher levels of quiescence (but contributed strongly to injury recovery). Both numerical and analytical results are presented.

  19. Consequences of plant invasions on compartmentalization and species' roles in plant-pollinator networks.

    PubMed

    Albrecht, Matthias; Padrón, Benigno; Bartomeus, Ignasi; Traveset, Anna

    2014-08-01

    Compartmentalization-the organization of ecological interaction networks into subsets of species that do not interact with other subsets (true compartments) or interact more frequently among themselves than with other species (modules)-has been identified as a key property for the functioning, stability and evolution of ecological communities. Invasions by entomophilous invasive plants may profoundly alter the way interaction networks are compartmentalized. We analysed a comprehensive dataset of 40 paired plant-pollinator networks (invaded versus uninvaded) to test this hypothesis. We show that invasive plants have higher generalization levels with respect to their pollinators than natives. The consequences for network topology are that-rather than displacing native species from the network-plant invaders attracting pollinators into invaded modules tend to play new important topological roles (i.e. network hubs, module hubs and connectors) and cause role shifts in native species, creating larger modules that are more connected among each other. While the number of true compartments was lower in invaded compared with uninvaded networks, the effect of invasion on modularity was contingent on the study system. Interestingly, the generalization level of the invasive plants partially explains this pattern, with more generalized invaders contributing to a lower modularity. Our findings indicate that the altered interaction structure of invaded networks makes them more robust against simulated random secondary species extinctions, but more vulnerable when the typically highly connected invasive plants go extinct first. The consequences and pathways by which biological invasions alter the interaction structure of plant-pollinator communities highlighted in this study may have important dynamical and functional implications, for example, by influencing multi-species reciprocal selection regimes and coevolutionary processes.

  20. Tissue-specific compartmental analysis for dynamic contrast-enhanced MR imaging of complex tumors.

    PubMed

    Chen, Li; Choyke, Peter L; Chan, Tsung-Han; Chi, Chong-Yung; Wang, Ge; Wang, Yue

    2011-12-01

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides a noninvasive method for evaluating tumor vasculature patterns based on contrast accumulation and washout. However, due to limited imaging resolution and tumor tissue heterogeneity, tracer concentrations at many pixels often represent a mixture of more than one distinct compartment. This pixel-wise partial volume effect (PVE) would have profound impact on the accuracy of pharmacokinetics studies using existing compartmental modeling (CM) methods. We, therefore, propose a convex analysis of mixtures (CAM) algorithm to explicitly mitigate PVE by expressing the kinetics in each pixel as a nonnegative combination of underlying compartments and subsequently identifying pure volume pixels at the corners of the clustered pixel time series scatter plot simplex. The algorithm is supported theoretically by a well-grounded mathematical framework and practically by plug-in noise filtering and normalization preprocessing. We demonstrate the principle and feasibility of the CAM-CM approach on realistic synthetic data involving two functional tissue compartments, and compare the accuracy of parameter estimates obtained with and without PVE elimination using CAM or other relevant techniques. Experimental results show that CAM-CM achieves a significant improvement in the accuracy of kinetic parameter estimation. We apply the algorithm to real DCE-MRI breast cancer data and observe improved pharmacokinetic parameter estimation, separating tumor tissue into regions with differential tracer kinetics on a pixel-by-pixel basis and revealing biologically plausible tumor tissue heterogeneity patterns. This method combines the advantages of multivariate clustering, convex geometry analysis, and compartmental modeling approaches. The open-source MATLAB software of CAM-CM is publicly available from the Web. PMID:21708498

  1. Probabilistic geomechanical analysis of compartmentalization at the Snøhvit CO2 sequestration project

    NASA Astrophysics Data System (ADS)

    Chiaramonte, Laura; White, Joshua A.; Trainor-Guitton, Whitney

    2015-02-01

    Pressure buildup caused by large-scale CO2 injection is a key concern during a carbon sequestration project. Large overpressures can compromise seal integrity, reactivate faults, and induce seismicity. Furthermore, pressure buildup is directly related with storage capacity. In this work we study the geomechanical response to CO2 injection at Snøhvit, to understand the potential for fault reactivation, leakage, and contamination of the producing interval through bounding faults. Furthermore, we evaluate the potential contribution of a structural component to reservoir compartmentalization. We combine simplified analytical models, based on critically stressed fracture theory and a Mohr-Coulomb failure criterion, with a rigorous sensitivity analysis. Large stress uncertainties are present and reflected in the modeling results. It was found that under the most likely stress state the faults are fairly stable and caprock hydrofracturing would be expected before fault reactivation. In most of the analyzed cases, the critical pressure perturbation needed for reactivation is above 13 MPa, which was the limiting pressure increase before reaching the fracture pressure. Faults were found to be ~ 20% less stable when considering variations in SHmax orientation. In those cases, fault reactivation could be expected before caprock failure if injection continued. However, if the pressure increase did reach the critical values for seal failure estimated under the worst case (and least likely) stress state, no indication of such failure can be observed in the measured pressure response. Finally, the potential role of a structural component in the compartmentalization and fluid migration is difficult to assess due to the stress state uncertainty.

  2. Pathway Compartmentalization in Peroxisome of Saccharomyces cerevisiae to Produce Versatile Medium Chain Fatty Alcohols.

    PubMed

    Sheng, Jiayuan; Stevens, Joseph; Feng, Xueyang

    2016-01-01

    Fatty alcohols are value-added chemicals and important components of a variety of industries, which have a >3 billion-dollar global market annually. Long chain fatty alcohols (>C12) are mainly used in surfactants, lubricants, detergents, pharmaceuticals and cosmetics while medium chain fatty alcohols (C6-C12) could be used as diesel-like biofuels. Microbial production of fatty alcohols from renewable feedstock stands as a promising strategy to enable sustainable supply of fatty alcohols. In this study, we report, for the first time, that medium chain fatty alcohols could be produced in yeast via targeted expression of a fatty acyl-CoA reductase (TaFAR) in the peroxisome of Saccharomyces cerevisiae. By tagging TaFAR enzyme with peroxisomal targeting signal peptides, the TaFAR could be compartmentalized into the matrix of the peroxisome to hijack the medium chain fatty acyl-CoA generated from the beta-oxidation pathway and convert them to versatile medium chain fatty alcohols (C10 &C12). The overexpression of genes encoding PEX7 and acetyl-CoA carboxylase further improved fatty alcohol production by 1.4-fold. After medium optimization in fed-batch fermentation using glucose as the sole carbon source, fatty alcohols were produced at 1.3 g/L, including 6.9% 1-decanol, 27.5% 1-dodecanol, 2.9% 1-tetradecanol and 62.7% 1-hexadecanol. This work revealed that peroxisome could be engineered as a compartmentalized organelle for producing fatty acid-derived chemicals in S. cerevisiae. PMID:27230732

  3. Cellular compartmentation of cadmium and zinc in relation to other elements in the hyperaccumulator Arabidopsis halleri.

    PubMed

    Küpper, H; Lombi, E; Zhao, F J; McGrath, S P

    2000-12-01

    The cellular compartmentation of elements was analysed in the Zn hyperaccumulator Arabidopsis halleri (L.) O'Kane & Al-Shehbaz (=Cardaminopsis halleri) using energy-dispersive X-ray microanalysis of frozen-hydrated tissues. Quantitative data were obtained using oxygen as an internal standard in the analyses of vacuoles, whereas a peak/background ratio method was used for quantification of elements in pollen and dehydrated trichomes. Arabidopsis halleri was found to hyperaccumulate not only Zn but also Cd in the shoot biomass. While large concentrations of Zn and Cd were found in the leaves and roots, flowers contained very little. In roots grown hydroponically, Zn and Cd accumulated in the cell wall of the rhizodermis (root epidermis), mainly due to precipitation of Zn/Cd phosphates. In leaves, the trichomes had by far the largest concentrations of Zn and Cd. Inside the trichomes there was a striking sub-cellular compartmentation, with almost all the Zn and Cd being accumulated in a narrow ring in the trichome base. This distribution pattern was very different from that for Ca and P. The epidermal cells other than trichomes were very small and contained lower concentrations of Zn and Cd than mesophyll cells. In particular, the concentrations of Cd and Zn in the mesophyll cells increased markedly in response to increasing Zn and Cd concentrations in the nutrient solution. This indicates that the mesophyll cells in the leaves of A. halleri are the major storage site for Zn and Cd, and play an important role in their hyperaccumulation.

  4. Compartmentalization of oxidative stress and antioxidant defense in the larval gut of Spodoptera littoralis.

    PubMed

    Krishnan, Natraj; Sehnal, Frantisek

    2006-09-01

    Allelochemicals play important roles in the plant defense against herbivorous insects. They act as feeding deterrents, interfere with digestion and nutrient absorption, and cause production of potentially dangerous oxidative radicals. This study demonstrates that the distributions of oxidative radicals and of the antioxidant enzymes that eliminate them are compartmentalized in the digestive tract of Spodoptera littoralis larvae. Feeding on diets supplemented with the tannic acid (TA), alpha-solanine, and demissidine, respectively, did not affect the rate of food passage through the digestive tract of larvae but 1.25, 2.5, and 5% TA evoked a strong oxidative response. The amount of the superoxide anion in the foregut tissue and content increased up to 70-fold and the titer of total peroxides in the foregut content about 3-fold. This oxidative stress was associated with enhanced carbonyl content in the foregut tissue proteins, indicative of certain tissue deterioration. Extensive foregut damage was probably prevented by elevated activity of the glutathione S-transferase peroxidase. A complex antioxidant response was elicited in the midgut. The activities of superoxide dismutase and catalase increased significantly in the midgut tissue and content, and the activity of ascorbate peroxidase rose in the midgut tissue. The enzymes apparently eliminated oxidative radicals passing to midgut from the foregut with the food bolus and thereby prevented carbonylation of the midgut proteins. We postulate that the generation of oxidative radicals in the foregut and the induction of antioxidant defense in the midgut are controlled processes and that their compartmentalization is an important functional feature of the digestive tract. The glycoalkaloid alpha-solanine and the aglycone demissidine applied at 0.05 and 0.1% concentrations had no effect on any of the examined parameters.

  5. The construction of next-generation matrices for compartmental epidemic models.

    PubMed

    Diekmann, O; Heesterbeek, J A P; Roberts, M G

    2010-06-01

    The basic reproduction number (0) is arguably the most important quantity in infectious disease epidemiology. The next-generation matrix (NGM) is the natural basis for the definition and calculation of (0) where finitely many different categories of individuals are recognized. We clear up confusion that has been around in the literature concerning the construction of this matrix, specifically for the most frequently used so-called compartmental models. We present a detailed easy recipe for the construction of the NGM from basic ingredients derived directly from the specifications of the model. We show that two related matrices exist which we define to be the NGM with large domain and the NGM with small domain. The three matrices together reflect the range of possibilities encountered in the literature for the characterization of (0). We show how they are connected and how their construction follows from the basic model ingredients, and establish that they have the same non-zero eigenvalues, the largest of which is the basic reproduction number (0). Although we present formal recipes based on linear algebra, we encourage the construction of the NGM by way of direct epidemiological reasoning, using the clear interpretation of the elements of the NGM and of the model ingredients. We present a selection of examples as a practical guide to our methods. In the appendix we present an elementary but complete proof that (0) defined as the dominant eigenvalue of the NGM for compartmental systems and the Malthusian parameter r, the real-time exponential growth rate in the early phase of an outbreak, are connected by the properties that (0) > 1 if and only if r > 0, and (0) = 1 if and only if r = 0. PMID:19892718

  6. Subcellular Compartmentation of the Diterpene Carnosic Acid and Its Derivatives in the Leaves of Rosemary1

    PubMed Central

    Munné-Bosch, Sergi; Alegre, Leonor

    2001-01-01

    The potent antioxidant properties of rosemary (Rosmarinus officinalis) extracts have been attributed to its major diterpene, carnosic acid. Carnosic acid has received considerable attention in food science and biomedicine, but little is known about its function in the plant in vivo. We recently found that highly oxidized diterpenes increase in rosemary plants exposed to drought and high light stress as a result of the antioxidant activity of carnosic acid (S. Munné-Bosch, K. Schwarz, L. Alegre [1999] Plant Physiol 121: 1047–1052). To elucidate the significance of the antioxidant function of carnosic acid in vivo we measured the relative amounts of carnosic acid and its metabolites in different compartments of rosemary leaves. Subcellular localization studies show that carnosic acid protects chloroplasts from oxidative stress in vivo by following a highly regulated compartmentation of oxidation products. Carnosic acid scavenges free radicals within the chloroplasts, giving rise to diterpene alcohols, mainly isorosmanol. This oxidation product is O-methylated within the chloroplasts, and the resulting form, 11,12-di-O-methylisorosmanol, is transferred to the plasma membrane. This appears to represent a mechanism of a way out for free radicals from chloroplasts. Carnosic acid also undergoes direct O-methylation within the chloroplasts, and its derived product, 12-O-methylcarnosic acid, accumulates in the plasma membrane. O-methylated diterpenes do not display antioxidant activity, but they may influence the stability of the plasma membrane. This study shows the relevance of the compartmentation of carnosic acid metabolism to the protection of rosemary plants from oxidative stress in vivo. PMID:11161064

  7. Polyamine/Nucleotide Coacervates Provide Strong Compartmentalization of Mg²⁺, Nucleotides, and RNA.

    PubMed

    Frankel, Erica A; Bevilacqua, Philip C; Keating, Christine D

    2016-03-01

    Phase separation of aqueous solutions containing polyelectrolytes can lead to formation of dense, solute-rich liquid droplets referred to as coacervates, surrounded by a dilute continuous phase of much larger volume. This type of liquid-liquid phase separation is thought to help explain the appearance of polyelectrolyte-rich intracellular droplets in the cytoplasm and nucleoplasm of extant biological cells and may be relevant to protocellular compartmentalization of nucleic acids on the early Earth. Here we describe complex coacervates formed upon mixing the polycation poly(allylamine) (PAH, 15 kDa) with the anionic nucleotides adenosine 5'-mono-, di-, and triphosphate (AMP, ADP, and ATP). Droplet formation was observed over a wide range of pH and MgCl2 concentrations. The nucleotides themselves as well as Mg(2+) and RNA oligonucleotides were all extremely concentrated within the coacervates. Nucleotides present at just 2.5 mM in bulk solution had concentrations greater than 1 M inside the coacervate droplets. A solution with a total Mg(2+) concentration of 10 mM had 1-5 M Mg(2+) in the coacervates, and RNA random sequence (N54) partitioned ∼10,000-fold into the coacervates. Coacervate droplets are thus rich in nucleotides, Mg(2+), and RNA, providing a medium favorable for generating functional RNAs. Compartmentalization of nucleotides at high concentrations could have facilitated their polymerization to form oligonucleotides, which preferentially accumulate in the droplets. Locally high Mg(2+) concentrations could have aided folding and catalysis in an RNA world, making coacervate droplets an appealing platform for exploring protocellular environments. PMID:26844692

  8. Plant B vitamin pathways and their compartmentation: a guide for the perplexed.

    PubMed

    Gerdes, Svetlana; Lerma-Ortiz, Claudia; Frelin, Océane; Seaver, Samuel M D; Henry, Christopher S; de Crécy-Lagard, Valérie; Hanson, Andrew D

    2012-09-01

    The B vitamins and the cofactors derived from them are essential for life. B vitamin synthesis in plants is consequently as crucial to plants themselves as it is to humans and animals, whose B vitamin nutrition depends largely on plants. The synthesis and salvage pathways for the seven plant B vitamins are now broadly known, but certain enzymes and many transporters have yet to be identified, and the subcellular locations of various reactions are unclear. Although very substantial, what is not known about plant B vitamin pathways is regrettably difficult to discern from the literature or from biochemical pathway databases. Nor do databases accurately represent all that is known about B vitamin pathways-above all their compartmentation-because the facts are scattered throughout the literature, and thus hard to piece together. These problems (i) deter discoveries because newcomers to B vitamins cannot see which mysteries still need solving; and (ii) impede metabolic reconstruction and modelling of B vitamin pathways because genes for reactions or transport steps are missing. This review therefore takes a fresh approach to capture current knowledge of B vitamin pathways in plants. The synthesis pathways, key salvage routes, and their subcellular compartmentation are surveyed in depth, and encoded in the SEED database (http://pubseed.theseed.org/seedviewer.cgi?page=PlantGateway) for Arabidopsis and maize. The review itself and the encoded pathways specifically identify enigmatic or missing reactions, enzymes, and transporters. The SEED-encoded B vitamin pathway collection is a publicly available, expertly curated, one-stop resource for metabolic reconstruction and modeling.

  9. Pathway Compartmentalization in Peroxisome of Saccharomyces cerevisiae to Produce Versatile Medium Chain Fatty Alcohols

    PubMed Central

    Sheng, Jiayuan; Stevens, Joseph; Feng, Xueyang

    2016-01-01

    Fatty alcohols are value-added chemicals and important components of a variety of industries, which have a >3 billion-dollar global market annually. Long chain fatty alcohols (>C12) are mainly used in surfactants, lubricants, detergents, pharmaceuticals and cosmetics while medium chain fatty alcohols (C6–C12) could be used as diesel-like biofuels. Microbial production of fatty alcohols from renewable feedstock stands as a promising strategy to enable sustainable supply of fatty alcohols. In this study, we report, for the first time, that medium chain fatty alcohols could be produced in yeast via targeted expression of a fatty acyl-CoA reductase (TaFAR) in the peroxisome of Saccharomyces cerevisiae. By tagging TaFAR enzyme with peroxisomal targeting signal peptides, the TaFAR could be compartmentalized into the matrix of the peroxisome to hijack the medium chain fatty acyl-CoA generated from the beta-oxidation pathway and convert them to versatile medium chain fatty alcohols (C10 & C12). The overexpression of genes encoding PEX7 and acetyl-CoA carboxylase further improved fatty alcohol production by 1.4-fold. After medium optimization in fed-batch fermentation using glucose as the sole carbon source, fatty alcohols were produced at 1.3 g/L, including 6.9% 1-decanol, 27.5% 1-dodecanol, 2.9% 1-tetradecanol and 62.7% 1-hexadecanol. This work revealed that peroxisome could be engineered as a compartmentalized organelle for producing fatty acid-derived chemicals in S. cerevisiae. PMID:27230732

  10. Limited Near and Far Transfer Effects of Jungle Memory Working Memory Training on Learning Mathematics in Children with Attentional and Mathematical Difficulties

    PubMed Central

    Nelwan, Michel; Kroesbergen, Evelyn H.

    2016-01-01

    The goal of this randomized controlled trial was to investigate whether Jungle Memory working memory training (JM) affects performance on working memory tasks, performance in mathematics and gains made on a mathematics training (MT) in school aged children between 9–12 years old (N = 64) with both difficulties in mathematics, as well as attention and working memory. Children were randomly assigned to three groups and were trained in two periods: (1) JM first, followed by MT, (2) MT first, followed by JM, and (3) a control group that received MT only. Bayesian analyses showed possible short term effects of JM on near transfer measures of verbal working memory, but none on visual working memory. Furthermore, support was found for the hypothesis that children that received JM first, performed better after MT than children who did not follow JM first or did not train with JM at all. However, these effects could be explained at least partly by frequency of training effects, possibly due to motivational issues, and training-specific factors. Furthermore, it remains unclear whether the effects found on improving mathematics were actually mediated by gains in working memory. It is argued that JM might not train the components of working memory involved in mathematics sufficiently. Another possible explanation can be found in the training’s lack of adaptivity, therefore failing to provide the children with tailored instruction and feedback. Finally, it was hypothesized that, since effect sizes are generally small, training effects are bound to a critical period in development. PMID:27708595

  11. HIV-1 Nef sequence and functional compartmentalization in the gut is not due to differential cytotoxic T lymphocyte selective pressure.

    PubMed

    Lewis, Martha J; Frohnen, Patricia; Ibarrondo, F Javier; Reed, Diane; Iyer, Varun; Ng, Hwee L; Elliott, Julie; Yang, Otto O; Anton, Peter

    2013-01-01

    The gut is the largest lymphoid organ in the body and a site of active HIV-1 replication and immune surveillance. The gut is a reservoir of persistent infection in some individuals with fully suppressed plasma viremia on combination antiretroviral therapy (cART) although the cause of this persistence is unknown. The HIV-1 accessory protein Nef contributes to persistence through multiple functions including immune evasion and increasing infectivity. Previous studies showed that Nef's function is shaped by cytotoxic T lymphocyte (CTL) responses and that there are distinct populations of Nef within tissue compartments. We asked whether Nef's sequence and/or function are compartmentalized in the gut and how compartmentalization relates to local CTL immune responses. Primary nef quasispecies from paired plasma and sigmoid colon biopsies from chronically infected subjects not on therapy were sequenced and cloned into Env(-) Vpu(-) pseudotyped reporter viruses. CTL responses were mapped by IFN-γ ELISpot using expanded CD8+ cells from blood and gut with pools of overlapping peptides covering the entire HIV proteome. CD4 and MHC Class I Nef-mediated downregulation was measured by flow cytometry. Multiple tests indicated compartmentalization of nef sequences in 5 of 8 subjects. There was also compartmentalization of function with MHC Class I downregulation relatively well preserved, but significant loss of CD4 downregulation specifically by gut quasispecies in 5 of 7 subjects. There was no compartmentalization of CTL responses in 6 of 8 subjects, and the selective pressure on quasispecies correlated with the magnitude CTL response regardless of location. These results demonstrate that Nef adapts via diverse pathways to local selective pressures within gut mucosa, which may be predominated by factors other than CTL responses such as target cell availability. The finding of a functionally distinct population within gut mucosa offers some insight into how HIV-1 may persist in

  12. The paraveinal mesophyll of soybean leaves in relation to assimilate transfer and compartmentation : II. Structural, metabolic and compartmental changes during reproductive growth.

    PubMed

    Franceschi, V R; Giaquinta, R T

    1983-04-01

    Nitrogen and carbohydrate assimilates were temporally and spatially compartmented among various cell types in soybean (Glycine max L., Merr.) leaves during seed filling. The paraveinal mesophyll (PVM), a unique cell layer found in soybean, was demonstrated to function in the synthesis, compartmentation and remobilization of nitrogen reserves prior to and during the seed-filling stages. At anthesis, the PVM vacuoles contain substantial protein which completely disappears by two weeks into the seed filling. Distinct changes in the PVM cytoplasm, tonoplast and organelles were correlated with the presence or absence of the vacuolar material. Microautoradiography following the accumulation of several radiolabeled sugars and amino acids demonstrated the glycoprotein nature of the vacuolar material. Incorporation of methionine, leucine, glucose, and glucosamine resulted in heavy labelling of the PVM vacuole, in contrast to galactose, proline, and mannose which resulted in a much reduced labelling pattern. In addition, starch is unequally compartmented and degraded among the various leaf cells during seed filling. At the end of the photoperiod at the flowering stage, the highest starch accumulation was in the second palisade layer followed by the spongy mesophyll and the first (uppermost) palisade layer. Starch in the first palisade layer was completely degraded during the dark whereas the starch in the second palisade and spongy mesophyll was not remobilized to any appreciable extent. By mid-podfilling (approximately five weeks postanthesis) starch was absent in the first palisade layer at the end of the photoperiod while the second palisade and spongy mesophyll layers contained substantial starch. Starch was remobilized from these latter cells during the remainder of seed filling when current photosynthetic production is low. Structural changes associated with cell senescence first appear in the upper palisade layer and then progress (excluding the PVM) to the second

  13. Three-Dimensional Compartmentalization of Subsurface Ground Water Flow in Eastern North American Mesozoic Basins

    NASA Astrophysics Data System (ADS)

    Ryan, M. P.; Sutphin, D. M.; Daniels, D. L.; Pierce, H. A.; Smoot, J. P.

    2002-05-01

    An extensive network of diabase intrusions occurs in several of the largest Mesozoic basins of Eastern North America, including the Culpeper, Gettysburg, Newark, and Hartford basins. Within each, great dikes, inclined sheets, and lopoliths cut through the surrounding sandstones, siltstones, and conglomerates in ways that subdivide the regional subsurface flow field, and thus compartmentalize the basin. In the Culpeper basin, for example, the scale- and direction-dependent permeability of diabase spans the range 10-17 to 10-21 m2, whereas the permeability of the heavily fractured sediments is in the range 10-12 to 10-14 m2. Thus there is at least three, and upwards of nine, orders of magnitude difference in permeability between the diabase and the surrounding sediments. This great permeability contrast is at the heart of basin compartmentalization and the related subsurface hydrologic phenomena. In the Culpeper basin, our understanding of compartmentalization is guided by the following geological, geophysical, and hydrologic measurements and observations: (1) Short wavelength aeromagnetic anomalies constrain the geometry of the up-turned margins of diabase lopoliths. These lopoliths bound compartments horizontally and vertically; (2) Deep compartment structure has been resolved to 800 meters by in-situ AudioMagnetotelluric experiments; (3) Alignments of hornfels-hosted springs parallel to the diabase-hornfels contact along a compartment wall. We posit that eastward-migrating ground water is forced up and out to the surface when it comes into contact with the low permeability diabase at depth; (4) Direct observations of high fluid flow from bedding plane fractures within hornfels in the diabase-hornfels contact ``no-flow boundary condition'' region of a compartment's walls; (5) Direct drilling into and through a compartment's margins. Pumping yields within diabase are ~2 gal./min., whereas penetration of the compartment margins (drilling from diabase into the

  14. Engineering nanostructured polymer blends with controlled nanoparticle location for excellent microwave absorption: a compartmentalized approach.

    PubMed

    Biswas, Sourav; Kar, Goutam Prasanna; Bose, Suryasarathi

    2015-07-14

    In order to obtain better materials, control over the precise location of nanoparticles is indispensable. It is shown here that ordered arrangements of nanoparticles, possessing different characteristics (electrical/magnetic dipoles), in the blend structure can result in excellent microwave absorption. This is manifested from a high reflection loss of ca. -67 dB for the best blend structure designed here. To attenuate electromagnetic radiation, the key parameters of high electrical conductivity and large dielectric/magnetic loss are targeted here by including a conductive material [multiwall carbon nanotubes, MWNTs], ferroelectric nanostructured material with associated relaxations in the GHz frequency [barium titanate, BT] and lossy ferromagnetic nanoparticles [nickel ferrite, NF]. In this study, bi-continuous structures were designed using 50/50 (by wt) blends of polycarbonate (PC) and polyvinylidene fluoride (PVDF). The MWNTs were modified using an electron acceptor molecule, a derivative of perylenediimide, which facilitates π-π stacking with the nanotubes and stimulates efficient charge transport in the blends. The nanoscopic materials have specific affinity towards the PVDF phase. Hence, by introducing surface-active groups, an ordered arrangement can be tailored. To accomplish this, both BT and NF were first hydroxylated followed by the introduction of amine-terminal groups on the surface. The latter facilitated nucleophilic substitution reactions with PC and resulted in their precise location. In this study, we have shown for the first time that by a compartmentalized approach, superior EM attenuation can be achieved. For instance, when the nanoparticles were localized exclusively in the PVDF phase or in both the phases, the minimum reflection losses were ca. -18 dB (for the MWNT/BT mixture) and -29 dB (for the MWNT/NF mixture), and the shielding occurred primarily through reflection. Interestingly, by adopting the compartmentalized approach wherein the

  15. Compartmental modeling of PAH transport in soil column experiments under variably-saturated flow conditions

    NASA Astrophysics Data System (ADS)

    Sartori, F.; Sericano, J. L.; Wade, T. L.; Mohanty, B. P.

    2012-12-01

    Knowledge about the mobilization of polycyclic aromatic hydrocarbons (PAH) from PAH-laden soils or sediments is important to understand their bioavailability, and ultimately assess the environmental risk of PAH transport from surface soils into the groundwater. The transport and kinetics of three PAH from a spiked soil layer (2-3 cm soil depth), Phenanthrene-d10 (1900 ng/g), Naphthalene-d8 (1500 ng/g), and Pyrene-d10 (1800 ng/g), were investigated by performing a series of 8 rainfall events during 25 days in two large, replicate soil columns (length: 35 cm; diameter: 14.5 cm; 1 Pore Volume [PV]=2.29 L) under variably-saturated flow conditions. The water-methanol displacing solutions were at volumetric fractions of 0.3 and 0.6 during day 1 (E1) through E8 and E12-E22, respectively. Soil matric potential (h) was monitored at 5-cm and 20-cm depth and volumetric water content (θ) at 12.5-cm and 27.5-cm depth. Soil solution was sampled at 5 cm- (n=46) and 27.5-cm depth (n=46), and the effluent at the bottom of the column (n=163). HYDRUS-1D was used for inverse modeling of h and θ data and to predict θ at specific times and soil depth increments. First-order kinetics, compartmental models describing the transfer of PAH from the soil compartment to the soil solution compartment (desorption) and vice versa (sorption), were used to estimate mass transfer rates (φs, sorption; φd, desorption; φe, elimination), PAH mass in each compartment, and partition coefficients (Kd). Phenanthrene breakthrough curve could be interpreted through a two-parameter, two-compartment model corresponding to the common two-site sorption model, whose parameter estimates (and 95% confidence intervals) were φd=2.72 (2.31, 3.19) PV-1 and φe=4.67 (3.82, 5.7 ) PV-1. Naphthalene breakthrough curve followed a simple one-compartment elimination model, φe=2.0 (1.9, 2.1) PV-1, and that of Pyrene a three-parameter, two-compartment model, φs=0.0454 (0.00853, 0.0603) PV-1, φd=0.165 (0.0319, 0.855) PV

  16. Engineering nanostructured polymer blends with controlled nanoparticle location for excellent microwave absorption: a compartmentalized approach.

    PubMed

    Biswas, Sourav; Kar, Goutam Prasanna; Bose, Suryasarathi

    2015-07-14

    In order to obtain better materials, control over the precise location of nanoparticles is indispensable. It is shown here that ordered arrangements of nanoparticles, possessing different characteristics (electrical/magnetic dipoles), in the blend structure can result in excellent microwave absorption. This is manifested from a high reflection loss of ca. -67 dB for the best blend structure designed here. To attenuate electromagnetic radiation, the key parameters of high electrical conductivity and large dielectric/magnetic loss are targeted here by including a conductive material [multiwall carbon nanotubes, MWNTs], ferroelectric nanostructured material with associated relaxations in the GHz frequency [barium titanate, BT] and lossy ferromagnetic nanoparticles [nickel ferrite, NF]. In this study, bi-continuous structures were designed using 50/50 (by wt) blends of polycarbonate (PC) and polyvinylidene fluoride (PVDF). The MWNTs were modified using an electron acceptor molecule, a derivative of perylenediimide, which facilitates π-π stacking with the nanotubes and stimulates efficient charge transport in the blends. The nanoscopic materials have specific affinity towards the PVDF phase. Hence, by introducing surface-active groups, an ordered arrangement can be tailored. To accomplish this, both BT and NF were first hydroxylated followed by the introduction of amine-terminal groups on the surface. The latter facilitated nucleophilic substitution reactions with PC and resulted in their precise location. In this study, we have shown for the first time that by a compartmentalized approach, superior EM attenuation can be achieved. For instance, when the nanoparticles were localized exclusively in the PVDF phase or in both the phases, the minimum reflection losses were ca. -18 dB (for the MWNT/BT mixture) and -29 dB (for the MWNT/NF mixture), and the shielding occurred primarily through reflection. Interestingly, by adopting the compartmentalized approach wherein the

  17. Compartmental microfluidic system for studying muscle-neuron communication and neuromuscular junction maintenance.

    PubMed

    Ionescu, Ariel; Zahavi, Eitan Erez; Gradus, Tal; Ben-Yaakov, Keren; Perlson, Eran

    2016-02-01

    Molecular communication between the motoneuron and the muscle is vital for neuromuscular junction (NMJ) formation and maintenance. Disruption in the structure and function of NMJs is a hallmark of various neurodegenerative processes during both development and pathological events. Still due to the complexity of this process, it is very difficult to elucidate the cellular mechanisms underlying it, generating a keen interest for developing better tools for investigating it. Here we describe a simplified method to study mechanisms of NMJs formation, maintenance and disruption. A spinal cord explant from mice expressing the Hb9::GFP motoneuron marker is plated on one side of a compartmental chamber, and myotubes derived from muscle satellite progenitor cells are plated on the other. The GFP labeled motoneurons extend their axons via microgrooves in the chamber to innervate the muscle cells and to form functional in-vitro NMJs. Next we provide procedures to measure axon growth and to reliably quantify NMJ activity using imaging of both muscle contractions and fast intracellular calcium changes. This platform allows precise control, monitoring and manipulation of subcellular microenvironments. Specifically, it enables to distinguish local from retrograde signaling mechanisms and allows restricted experimental intervention in local compartments along the muscle-neuron route. PMID:26689471

  18. Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units.

    PubMed

    Uzel, Sebastien G M; Platt, Randall J; Subramanian, Vidya; Pearl, Taylor M; Rowlands, Christopher J; Chan, Vincent; Boyer, Laurie A; So, Peter T C; Kamm, Roger D

    2016-08-01

    Motor units are the fundamental elements responsible for muscle movement. They are formed by lower motor neurons and their muscle targets, synapsed via neuromuscular junctions (NMJs). The loss of NMJs in neurodegenerative disorders (such as amyotrophic lateral sclerosis or spinal muscle atrophy) or as a result of traumatic injuries affects millions of lives each year. Developing in vitro assays that closely recapitulate the physiology of neuromuscular tissues is crucial to understand the formation and maturation of NMJs, as well as to help unravel the mechanisms leading to their degeneration and repair. We present a microfluidic platform designed to coculture myoblast-derived muscle strips and motor neurons differentiated from mouse embryonic stem cells (ESCs) within a three-dimensional (3D) hydrogel. The device geometry mimics the spinal cord-limb physical separation by compartmentalizing the two cell types, which also facilitates the observation of 3D neurite outgrowth and remote muscle innervation. Moreover, the use of compliant pillars as anchors for muscle strips provides a quantitative functional readout of force generation. Finally, photosensitizing the ESC provides a pool of source cells that can be differentiated into optically excitable motor neurons, allowing for spatiodynamic, versatile, and noninvasive in vitro control of the motor units. PMID:27493991

  19. Hypothalamic metabolic compartmentation during appetite regulation as revealed by magnetic resonance imaging and spectroscopy methods

    PubMed Central

    Lizarbe, Blanca; Benitez, Ania; Peláez Brioso, Gerardo A.; Sánchez-Montañés, Manuel; López-Larrubia, Pilar; Ballesteros, Paloma; Cerdán, Sebastián

    2013-01-01

    We review the role of neuroglial compartmentation and transcellular neurotransmitter cycling during hypothalamic appetite regulation as detected by Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) methods. We address first the neurochemical basis of neuroendocrine regulation in the hypothalamus and the orexigenic and anorexigenic feed-back loops that control appetite. Then we examine the main MRI and MRS strategies that have been used to investigate appetite regulation. Manganese-enhanced magnetic resonance imaging (MEMRI), Blood oxygenation level-dependent contrast (BOLD), and Diffusion-weighted magnetic resonance imaging (DWI) have revealed Mn2+ accumulations, augmented oxygen consumptions, and astrocytic swelling in the hypothalamus under fasting conditions, respectively. High field 1H magnetic resonance in vivo, showed increased hypothalamic myo-inositol concentrations as compared to other cerebral structures. 1H and 13C high resolution magic angle spinning (HRMAS) revealed increased neuroglial oxidative and glycolytic metabolism, as well as increased hypothalamic glutamatergic and GABAergic neurotransmissions under orexigenic stimulation. We propose here an integrative interpretation of all these findings suggesting that the neuroendocrine regulation of appetite is supported by important ionic and metabolic transcellular fluxes which begin at the tripartite orexigenic clefts and become extended spatially in the hypothalamus through astrocytic networks becoming eventually MRI and MRS detectable. PMID:23781199

  20. Technology Solutions Case Study: Apartment Compartmentalization with an Aerosol-Based Sealing Process

    SciTech Connect

    2015-07-01

    Air sealing of building enclosures is a difficult and time-consuming process. Current methods in new construction require laborers to physically locate small and sometimes large holes in multiple assemblies and then manually seal each of them. This research study by Building America team Consortium for Advanced Residential Buildings demonstrated the automated air sealing and compartmentalization of buildings through the use of an aerosolized sealant developed by the Western Cooling Efficiency Center at University of California Davis. CARB demonstrated this new technology application in a multifamily building in Queens, NY. The effectiveness of the sealing process was evaluated by three methods: air leakage testing of overall apartment before and after sealing, point-source testing of individual leaks, and pressure measurements in the walls of the target apartment during sealing. Aerosolized sealing was successful by several measures in this study. Many individual leaks that are labor-intensive to address separately were well sealed by the aerosol particles. In addition, many diffuse leaks that are difficult to identify and treat were also sealed. The aerosol-based sealing process resulted in an average reduction of 71% in air leakage across three apartments and an average apartment airtightness of 0.08 CFM50/SF of enclosure area.

  1. PGI2 synthesis and excretion in dog kidney: evidence for renal PG compartmentalization

    SciTech Connect

    Boyd, R.M.; Nasjletti, A.; Heerdt, P.M.; Baer, P.G.

    1986-01-01

    To assess the concept of compartmentalization of renal prostaglandins (PG), we compared entry of PGE2 and the PGI2 metabolite 6-keto-PGF1 alpha into the renal vascular and tubular compartments, in sodium pentobarbital-anesthetized dogs. Renal arterial 6-keto-PGF1 alpha infusion increased both renal venous and urinary 6-keto-PGF1 alpha outflow. In contrast, renal arterial infusion of arachidonic acid (AA) or bradykinin (BK) increased renal venous 6-keto-PGF1 alpha outflow but had no effect on its urinary outflow. Both urinary and renal venous PGE2 outflows increased during AA or BK infusion. Ureteral stopped-flow studies revealed no postglomerular 6-keto-PGF1 alpha entry into tubular fluid. During renal arterial infusion of (3H)PGI2 and inulin, first-pass 3H clearance was 40% of inulin clearance; 35% of urinary 3H was 6-keto-PGF1 alpha, and two other urinary metabolites were found. During renal arterial infusion of (3H)6-keto-PGF1 alpha and inulin, first-pass 3H clearance was 150% of inulin clearance; 75% of urinary 3H was 6-keto-PGF1 alpha, and only one other metabolite was found. We conclude that in the dog PGE2 synthesized in the kidney enters directly into both the renal vascular and tubular compartments, but 6-keto-PGF1 alpha of renal origin enters directly into only the renal vascular compartment.

  2. The dynamics of gene amplification described as a multitype compartmental model and as a branching process.

    PubMed

    Harnevo, L E; Agur, Z

    1991-02-01

    The present work is aimed at developing the mathematical tools by which the dynamics of gene amplification (GA) can be described in detail. Some discrete compartmental models of GA by disproportionate replication and a general model for other putative GA mechanisms are presented and analyzed. The dynamical distribution of gene copy number in the cell population is calculated with the loss of cells taken either as constant or as copy-number-dependent. Our analysis shows that for a one-copy GA process with constant loss of cells, the relative frequency of single-gene-copy cells (sensitive cells) converges to zero, with the rate of convergence depending on the amplification probability. In contrast, for a one-copy GA process with copy-number-dependent loss of cells, the relative frequency of single-copy cells is bounded, implying a bounded compartment of many-gene-copy cells. Using branching processes theory we calculate the dynamical distribution of the single-gene-copy compartment as well as its extinction probability. Our models are used for estimating treatment prognosis as affected by drug resistance due to GA, showing significant differences in prognosis resulting from small changes in drug dose.

  3. An Amino Terminal Phosphorylation Motif Regulates Intranuclear Compartmentalization of Olig2 in Neural Progenitor Cells

    PubMed Central

    Meijer, Dimphna H.; Sun, Yu; Liu, Tao; Kane, Michael F.; Alberta, John A.; Adelmant, Guillaume; Kupp, Robert; Marto, Jarrod A.; Rowitch, David H.; Nakatani, Yoshihiro

    2014-01-01

    The bHLH transcription factor Olig2 is expressed in cycling neural progenitor cells but also in terminally differentiated, myelinating oligodendrocytes. Sustained expression of Olig2 is counterintuitive because all known functions of the protein in expansion of neural progenitors and specification of oligodendrocyte progenitors are completed with the formation of mature white matter. How are the biological functions of Olig2 suppressed in terminally differentiated oligodendrocytes? In previous studies, we have shown that a triple serine motif in the amino terminus of Olig2 is phosphorylated in cycling neural progenitors but not in their differentiated progeny. We now show that phosphorylation of the triple serine motif regulates intranuclear compartmentalization of murine Olig2. Phosphorylated Olig2 is preferentially localized to a transcriptionally active “open” chromatin compartment together with coregulator proteins essential for regulation of gene expression. Unphosphorylated Olig2, as seen in mature white matter, is localized mainly within a transcriptionally inactive, chromatin fraction characterized by condensed and inaccessible DNA. Of special note is the observation that the p53 tumor suppressor protein is confined to the open chromatin fraction. Proximity ligation assays show that phosphorylation brings Olig2 within 30 nm of p53 within the open chromatin compartment. The data thus shed light on previously noted promitogenic functions of phosphorylated Olig2, which reflect, at least in part, an oppositional relationship with p53 functions. PMID:24948806

  4. The cytosolic chaperone α-crystallin B rescues folding and compartmentalization of misfolded multispan transmembrane proteins.

    PubMed

    D'Agostino, Massimo; Lemma, Valentina; Chesi, Giancarlo; Stornaiuolo, Mariano; Cannata Serio, Magda; D'Ambrosio, Chiara; Scaloni, Andrea; Polishchuk, Roman; Bonatti, Stefano

    2013-09-15

    The α-crystallin B chain (CRYAB or HspB5) is a cytosolic chaperone belonging to the small heat shock protein family, which is known to help in the folding of cytosolic proteins. Here we show that CRYAB binds the mutant form of at least two multispan transmembrane proteins (TMPs), exerting an anti-aggregation activity. It rescues the folding of mutant Frizzled4, which is responsible for a rare autosomal dominant form of familial exudative vitreoretinopathy (Fz4-FEVR), and the mutant ATP7B Cu transporter (ATP7B-H1069Q) associated with a common form of Wilson's disease. In the case of Fz4-FEVR, CRYAB prevents the formation of inter-chain disulfide bridges between the lumenal ectodomains of the aggregated mutant chains, which enables correct folding and promotes appropriate compartmentalization on the plasma membrane. ATP7B-H1069Q, with help from CRYAB, folds into the proper conformation, moves to the Golgi complex, and responds to copper overload in the same manner as wild-type ATP7B. These findings strongly suggest that CRYAB plays a pivotal role, previously undetected, in the folding of multispan TMPs and, from the cytosol, is able to orchestrate folding events that take place in the lumen of the ER. Our results contribute to the explanation of the complex scenario behind multispan TMP folding; additionally, they serve to expose interesting avenues for novel therapeutic approaches. PMID:23843626

  5. Integrated compartmental model for describing the transport of solute in a fractured porous medium. [FRACPORT

    SciTech Connect

    DeAngelis, D.L.; Yeh, G.T.; Huff, D.D.

    1984-10-01

    This report documents a model, FRACPORT, that simulates the transport of a solute through a fractured porous matrix. The model should be useful in analyzing the possible transport of radionuclides from shallow-land burial sites in humid environments. The use of the model is restricted to transport through saturated zones. The report first discusses the general modeling approach used, which is based on the Integrated Compartmental Method. The basic equations of solute transport are then presented. The model, which assumes a known water velocity field, solves these equations on two different time scales; one related to rapid transport of solute along fractures and the other related to slower transport through the porous matrix. FRACPORT is validated by application to a simple example of fractured porous medium transport that has previously been analyzed by other methods. Then its utility is demonstrated in analyzing more complex cases of pulses of solute into a fractured matrix. The report serves as a user's guide to FRACPORT. A detailed description of data input, along with a listing of input for a sample problem, is provided. 16 references, 18 figures, 3 tables.

  6. The anomalous kinetics of coupled aspartate aminotransferase and malate dehydrogenase. Evidence for compartmentation of oxaloacetate.

    PubMed Central

    Bryce, C F; Williams, D C; John, R A; Fasella, P

    1976-01-01

    Cytoplasmic aspartate aminotransferase and malate dehydrogenase were purified from pig heart. Kinetic parameters were determined for the separate reaction catalysed by each enzyme and used to predict the course of the coupled reaction: (see article). Although a lag phase should have been easily seen, none was detected. The same coupled reaction was also carried out by using radioactive aspartate in the presence of unlabelled oxaloacetate. The reaction was quenched with HClO4 after 70 ms and the specific radioactivity of the malate produced in this system was found to be essentially the same as that of the original aspartate. These results show that oxaloacetate produced by the aspartate aminotransferase is converted into malate by malate dehydrogenase before it equilibrates with the pool of unlabelled oxaloacetate and are consistent with a proposal that the enzymes are associated in a complex. However, no physical evidence of the existence of a complex could be found. An alternative means of compartmentation of the intermediate as an unstable isomer is considered. Images Fig. 2. Fig. 3. PMID:942372

  7. Fluvial architecture and reservoir compartmentalization in the Oligocene middle Frio Formation of south Texas

    SciTech Connect

    Kerr, D.R.; Jirik, L.A. )

    1990-09-01

    Seeligson, Stratton, and Agua Dulce fields are being studied as part of a Gas Research Institute/Department of Energy/State of Texas cosponsored program designed to develop and test methodologies and technologies for gas reserve growth in conventional reservoirs in mature gas fields. Over the last four decades, each field has produced approximately 2 tcf of gas from middle Frio reservoirs alone. Recent drilling and workover results and reservoir pressure data, however, point to the possibility of additional reserves. Stratigraphic and sedimentologic studies based on well logs and cores indicate that middle Frio reservoirs are architecturally complex. Deposition on an aggrading coastal plain resulted in a continuum of architectural styles that has important implications for reservoir compartmentalization. The middle Frio is composed of sand-rich channel-fill and splay deposits interstratified with floodplain mudstones, all forming part of the Gueydan fluvial system. Relatively slow aggradation resulted in laterally stacked channel systems; whereas more rapid aggradation resulted in vertically stacked channel systems. Laterally stacked sandstone bodies predominate at Seeligson field, leading to separate but potentially leaky reservoir compartments. By contrast, vertically stacked sandstone bodies predominate at Stratton and Agua Dulce fields, favoring more isolated reservoir compartments. Thus, a high potential for reserve growth through the identification of untapped compartments, poorly drained acreage, and bypassed zones exists for each of these fields, but differences in reservoir architecture must be taken into account as part of exploitation strategies.

  8. Modeling the time dependent biodistribution of Samarium-153 ethylenediamine tetramethylene phosphonate using compartmental analysis

    PubMed Central

    Abbasian, Parandoush; Foroghy, Monika; Jalilian, Amir Reza; Hakimi, Amir; Shirvani-Arani, Simindokht

    2013-01-01

    Aim The main purpose of this work was to develop a pharmacokinetic model for the bone pain palliation agent Samarium-153 ethylenediamine tetramethylene phosphonate ([153Sm]-EDTMP) in normal rats to analyze the behavior of the complex. Background The use of compartmental analysis allows a mathematical separation of tissues and organs to determine the concentration of activity in each fraction of interest. Biodistribution studies are expensive and difficult to carry out in humans, but such data can be obtained easily in rodents. Materials and methods We have developed a physiologically based pharmacokinetic model for scaling up activity concentration in each organ versus time. The mathematical model uses physiological parameters including organ volumes, blood flow rates, and vascular permabilities; the compartments (organs) are connected anatomically. This allows the use of scale-up techniques to predict new complex distribution in humans in each organ. Results The concentration of the radiopharmaceutical in various organs was measured at different times. The temporal behavior of biodistribution of 153Sm-EDTMP was modeled and drawn as a function of time. Conclusions The variation of pharmaceutical concentration in all organs is described with summation of 6–10 exponential terms and it approximates our experimental data with precision better than 2%. PMID:24936338

  9. Increasing the speed of relaxometry-based compartmental analysis experiments in STEAM spectroscopy

    NASA Astrophysics Data System (ADS)

    Knight-Scott, Jack; Dunham, S. Andrea; Shanbhag, Dattesh D.

    2005-03-01

    In this work we present a method for improving the speed of spin-spin relaxation time ( T2) measurements for compartmental analysis in stimulated echo localized magnetic resonance spectroscopy without reducing the sampling density. The technique uses a progressive repetition time (TR) to compensate for echo time (TE) dependent variations in saturation effects that would otherwise modulate the received signal at short TRs. The method was validated in T2 studies on 10 young healthy subjects in spectroscopic voxels localized along either the right or left Sylvian fissure (2 × 2 × 1.5 cm 3, 10 ms mixing time (TM), 2048 data points, 819.2 ms acquisition time). The TR was automatically adjusted so that TR-TM-TE/2 was kept constant as the TE was incremented. Compared to long TR T2 experiments, the progressive TR technique consistently replicated the T2 relaxation times and reference signals of the tissue water compartment while reducing the data acquisition time by more than 50%. The percent error was on average less than 2% for estimates of T2 and S0 for the tissue water, an indication that the progressive TR technique is a useful method for determining the tissue water signal for internal referencing.

  10. A multi-stage compartmental model for HIV-infected individuals: I--waiting time approach.

    PubMed

    Billard, L; Dayananda, P W A

    2014-03-01

    Traditionally, epidemic processes have focused on establishing systems of differential-difference equations governing the number of individuals at each stage of the epidemic. Except for simple situations such as when transition rates are linear, these equations are notoriously intractable mathematically. In this work, the process is described as a compartmental model. The model also allows for individuals to go directly from any prior compartment directly to a final stage corresponding to death. This allows for the possibility that individuals can die earlier due to some non-disease related cause. Then, the model is based on waiting times in each compartment. Survival probabilities of moving from a given compartment to another compartment are established. While our approach can be used for general epidemic processes, our framework is for the HIV/AIDS process. It is then possible to establish the impact of the HIV/AIDS epidemic process on, e.g., insurance premiums and payouts and health-care costs. The effect of changing model parameter values on these entities is investigated.

  11. A Tale of Genome Compartmentalization: The Evolution of Virulence Clusters in Smut Fungi.

    PubMed

    Dutheil, Julien Y; Mannhaupt, Gertrud; Schweizer, Gabriel; M K Sieber, Christian; Münsterkötter, Martin; Güldener, Ulrich; Schirawski, Jan; Kahmann, Regine

    2016-03-01

    Smut fungi are plant pathogens mostly parasitizing wild species of grasses as well as domesticated cereal crops. Genome analysis of several smut fungi including Ustilago maydis revealed a singular clustered organization of genes encoding secreted effectors. In U. maydis, many of these clusters have a role in virulence. Reconstructing the evolutionary history of clusters of effector genes is difficult because of their intrinsically fast evolution, which erodes the phylogenetic signal and homology relationships. Here, we describe the use of comparative evolutionary analyses of quality draft assemblies of genomes to study the mechanisms of this evolution. We report the genome sequence of a South African isolate of Sporisorium scitamineum, a smut fungus parasitizing sugar cane with a phylogenetic position intermediate to the two previously sequenced species U. maydis and Sporisorium reilianum. We show that the genome of S. scitamineum contains more and larger gene clusters encoding secreted effectors than any previously described species in this group. We trace back the origin of the clusters and find that their evolution is mainly driven by tandem gene duplication. In addition, transposable elements play a major role in the evolution of the clustered genes. Transposable elements are significantly associated with clusters of genes encoding fast evolving secreted effectors. This suggests that such clusters represent a case of genome compartmentalization that restrains the activity of transposable elements on genes under diversifying selection for which this activity is potentially beneficial, while protecting the rest of the genome from its deleterious effect. PMID:26872771

  12. A Tale of Genome Compartmentalization: The Evolution of Virulence Clusters in Smut Fungi

    PubMed Central

    Dutheil, Julien Y.; Mannhaupt, Gertrud; Schweizer, Gabriel; M.K. Sieber, Christian; Münsterkötter, Martin; Güldener, Ulrich; Schirawski, Jan; Kahmann, Regine

    2016-01-01

    Smut fungi are plant pathogens mostly parasitizing wild species of grasses as well as domesticated cereal crops. Genome analysis of several smut fungi including Ustilago maydis revealed a singular clustered organization of genes encoding secreted effectors. In U. maydis, many of these clusters have a role in virulence. Reconstructing the evolutionary history of clusters of effector genes is difficult because of their intrinsically fast evolution, which erodes the phylogenetic signal and homology relationships. Here, we describe the use of comparative evolutionary analyses of quality draft assemblies of genomes to study the mechanisms of this evolution. We report the genome sequence of a South African isolate of Sporisorium scitamineum, a smut fungus parasitizing sugar cane with a phylogenetic position intermediate to the two previously sequenced species U. maydis and Sporisorium reilianum. We show that the genome of S. scitamineum contains more and larger gene clusters encoding secreted effectors than any previously described species in this group. We trace back the origin of the clusters and find that their evolution is mainly driven by tandem gene duplication. In addition, transposable elements play a major role in the evolution of the clustered genes. Transposable elements are significantly associated with clusters of genes encoding fast evolving secreted effectors. This suggests that such clusters represent a case of genome compartmentalization that restrains the activity of transposable elements on genes under diversifying selection for which this activity is potentially beneficial, while protecting the rest of the genome from its deleterious effect. PMID:26872771

  13. Compartmentalized Epidermal Activation of β-Catenin Differentially Affects Lineage Reprogramming and Underlies Tumor Heterogeneity.

    PubMed

    Kretzschmar, Kai; Weber, Christine; Driskell, Ryan R; Calonje, Eduardo; Watt, Fiona M

    2016-01-12

    Wnt/β-catenin activation in adult epidermis can induce new hair follicle formation and tumor development. We used lineage tracing to uncover the relative contribution of different stem cell populations. LGR6(+) and LRIG1(+) stem cells contributed to ectopic hair follicles formed in the sebaceous gland upon β-catenin activation, whereas LGR5(+) cells did not. Lgr6, but not Lrig1 or Lgr5, was expressed in a subpopulation of interfollicular epidermal cells that were competent to form new hair follicles. Oncogenic β-catenin expression in LGR5(+) cells led to formation of pilomatricomas, while LRIG1(+) cells formed trichoadenomas and LGR6(+) cells formed dermatofibromas. Tumor formation was always accompanied by a local increase in dermal fibroblast density and transient extracellular matrix remodeling. However, each tumor had a distinct stromal signature in terms of immune cell infiltrate and expression of CD26 and CD44. We conclude that compartmentalization of epidermal stem cells underlies different responses to β-catenin and skin tumor heterogeneity. PMID:26771241

  14. Modeling Heterogeneity in Direct Infectious Disease Transmission in a Compartmental Model

    PubMed Central

    Kong, Lingcai; Wang, Jinfeng; Han, Weiguo; Cao, Zhidong

    2016-01-01

    Mathematical models have been used to understand the transmission dynamics of infectious diseases and to assess the impact of intervention strategies. Traditional mathematical models usually assume a homogeneous mixing in the population, which is rarely the case in reality. Here, we construct a new transmission function by using as the probability density function a negative binomial distribution, and we develop a compartmental model using it to model the heterogeneity of contact rates in the population. We explore the transmission dynamics of the developed model using numerical simulations with different parameter settings, which characterize different levels of heterogeneity. The results show that when the reproductive number, R0, is larger than one, a low level of heterogeneity results in dynamics similar to those predicted by the homogeneous mixing model. As the level of heterogeneity increases, the dynamics become more different. As a test case, we calibrated the model with the case incidence data for severe acute respiratory syndrome (SARS) in Beijing in 2003, and the estimated parameters demonstrated the effectiveness of the control measures taken during that period. PMID:26927140

  15. A coherent neurobiological framework for functional neuroimaging provided by a model integrating compartmentalized energy metabolism.

    PubMed

    Aubert, Agnès; Pellerin, Luc; Magistretti, Pierre J; Costalat, Robert

    2007-03-01

    Functional neuroimaging has undergone spectacular developments in recent years. Paradoxically, its neurobiological bases have remained elusive, resulting in an intense debate around the cellular mechanisms taking place upon activation that could contribute to the signals measured. Taking advantage of a modeling approach, we propose here a coherent neurobiological framework that not only explains several in vitro and in vivo observations but also provides a physiological basis to interpret imaging signals. First, based on a model of compartmentalized energy metabolism, we show that complex kinetics of NADH changes observed in vitro can be accounted for by distinct metabolic responses in two cell populations reminiscent of neurons and astrocytes. Second, extended application of the model to an in vivo situation allowed us to reproduce the evolution of intraparenchymal oxygen levels upon activation as measured experimentally without substantially altering the initial parameter values. Finally, applying the same model to functional neuroimaging in humans, we were able to determine that the early negative component of the blood oxygenation level-dependent response recorded with functional MRI, known as the initial dip, critically depends on the oxidative response of neurons, whereas the late aspects of the signal correspond to a combination of responses from cell types with two distinct metabolic profiles that could be neurons and astrocytes. In summary, our results, obtained with such a modeling approach, support the concept that both neuronal and glial metabolic responses form essential components of neuroimaging signals. PMID:17360498

  16. Dorsoventral compartmentalization of mesoderm in heart-forming area of chick embryo.

    PubMed

    Kärner, M; Krinka, D; Padari, K; Kärner, J; Raid, R

    2000-06-01

    In early chick development (stages 5-8) the seemingly homogeneous mesoderm in the heart-forming area splits to somatic and splanchnic cardiogenic layers. Little is known about dorsoventral compartmentalization before splitting. Electron microscopic analysis shows the early dorsoventral polarization of precardiomyocytes. The dorsal compartment has epithelial and the ventral compartment mesenchymal features with numerous protrusions. At stage 5+-6 staining for wheat germ agglutinine (WGA) transiently demarcates the ventral part of mesoderm. The glycosomes (beta-glycogen) show a dorsoventral gradient in the mesoderm of the cardiogenic field during the initial step of the compaction. The differential expression of glycosomes depends on the activity of glycogen synthase kinase 3-beta, a component of the wnt-signaling pathway, and might in this spatiotemporal developmental window be involved in the commitment of presumptive cardiogenic and somatic cells. To verify this hypothesis simulation experiments with LiCl in vitro were carried out. The normal splitting of the mesoderm and the development of heart primordia were disturbed. Blocking the receptors of WGA by WGA in vitro at stage 5-5+ perturbs the migration of mesoderm to anterio-medial direction. It appears that early specification of dorsal and ventral compartments of the mesoderm in the heart-forming area correlates with the gradient of glycosomes. Our results suggest that the target of LiCl action (glycogen synthase kinase 3-beta) might be involved in the specification of heart primordia and that WGA receptors mediate the migration of mesoderm to the anteriomedial direction.

  17. Linear least squares compartmental-model-independent parameter identification in PET.

    PubMed

    Thie, J A; Smith, G T; Hubner, K F

    1997-02-01

    A simplified approach involving linear-regression straight-line parameter fitting of dynamic scan data is developed for both specific and nonspecific models. Where compartmental-model topologies apply, the measured activity may be expressed in terms of: its integrals, plasma activity and plasma integrals--all in a linear expression with macroparameters as coefficients. Multiple linear regression, as in spreadsheet software, determines parameters for best data fits. Positron emission tomography (PET)-acquired gray-matter images in a dynamic scan are analyzed: both by this method and by traditional iterative nonlinear least squares. Both patient and simulated data were used. Regression and traditional methods are in expected agreement. Monte-Carlo simulations evaluate parameter standard deviations, due to data noise, and much smaller noise-induced biases. Unique straight-line graphical displays permit visualizing data influences on various macroparameters as changes in slopes. Advantages of regression fitting are: simplicity, speed, ease of implementation in spreadsheet software, avoiding risks of convergence failures or false solutions in iterative least squares, and providing various visualizations of the uptake process by straight line graphical displays. Multiparameter model-independent analyses on lesser understood systems is also made possible.

  18. Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units

    PubMed Central

    Uzel, Sebastien G. M.; Platt, Randall J.; Subramanian, Vidya; Pearl, Taylor M.; Rowlands, Christopher J.; Chan, Vincent; Boyer, Laurie A.; So, Peter T. C.; Kamm, Roger D.

    2016-01-01

    Motor units are the fundamental elements responsible for muscle movement. They are formed by lower motor neurons and their muscle targets, synapsed via neuromuscular junctions (NMJs). The loss of NMJs in neurodegenerative disorders (such as amyotrophic lateral sclerosis or spinal muscle atrophy) or as a result of traumatic injuries affects millions of lives each year. Developing in vitro assays that closely recapitulate the physiology of neuromuscular tissues is crucial to understand the formation and maturation of NMJs, as well as to help unravel the mechanisms leading to their degeneration and repair. We present a microfluidic platform designed to coculture myoblast-derived muscle strips and motor neurons differentiated from mouse embryonic stem cells (ESCs) within a three-dimensional (3D) hydrogel. The device geometry mimics the spinal cord–limb physical separation by compartmentalizing the two cell types, which also facilitates the observation of 3D neurite outgrowth and remote muscle innervation. Moreover, the use of compliant pillars as anchors for muscle strips provides a quantitative functional readout of force generation. Finally, photosensitizing the ESC provides a pool of source cells that can be differentiated into optically excitable motor neurons, allowing for spatiodynamic, versatile, and noninvasive in vitro control of the motor units. PMID:27493991

  19. An amino terminal phosphorylation motif regulates intranuclear compartmentalization of Olig2 in neural progenitor cells.

    PubMed

    Meijer, Dimphna H; Sun, Yu; Liu, Tao; Kane, Michael F; Alberta, John A; Adelmant, Guillaume; Kupp, Robert; Marto, Jarrod A; Rowitch, David H; Nakatani, Yoshihiro; Stiles, Charles D; Mehta, Shwetal

    2014-06-18

    The bHLH transcription factor Olig2 is expressed in cycling neural progenitor cells but also in terminally differentiated, myelinating oligodendrocytes. Sustained expression of Olig2 is counterintuitive because all known functions of the protein in expansion of neural progenitors and specification of oligodendrocyte progenitors are completed with the formation of mature white matter. How are the biological functions of Olig2 suppressed in terminally differentiated oligodendrocytes? In previous studies, we have shown that a triple serine motif in the amino terminus of Olig2 is phosphorylated in cycling neural progenitors but not in their differentiated progeny. We now show that phosphorylation of the triple serine motif regulates intranuclear compartmentalization of murine Olig2. Phosphorylated Olig2 is preferentially localized to a transcriptionally active "open" chromatin compartment together with coregulator proteins essential for regulation of gene expression. Unphosphorylated Olig2, as seen in mature white matter, is localized mainly within a transcriptionally inactive, chromatin fraction characterized by condensed and inaccessible DNA. Of special note is the observation that the p53 tumor suppressor protein is confined to the open chromatin fraction. Proximity ligation assays show that phosphorylation brings Olig2 within 30 nm of p53 within the open chromatin compartment. The data thus shed light on previously noted promitogenic functions of phosphorylated Olig2, which reflect, at least in part, an oppositional relationship with p53 functions. PMID:24948806

  20. MRI investigation of subcellular water compartmentalization and gas distribution in apples.

    PubMed

    Winisdorffer, Guillaume; Musse, Maja; Quellec, Stéphane; Devaux, Marie-Françoise; Lahaye, Marc; Mariette, François

    2015-06-01

    Water status and distribution at subcellular level in whole apple fruit were evaluated by Magnetic Resonance Imaging (MRI) measurement of the multi-exponential transverse (T2) relaxation of water protons. Apparent microporosity, also estimated by MRI, provided mapping of gas distribution in fruit tissues. Measuring for the first time the multi-exponential relaxation of water and apparent tissue microporosity in whole fruit and combining these with histological measurements provided a more reliable interpretation of the origins of variations in the transverse relaxation time (T2) and better characterization of the fruit tissue. Measurements were performed on 54 fruits from 3 different cultivars. Fruits of different sizes were selected for each cultivar to provide tissues with cells of different dimensions. Macrovision measurements were carried out on parenchymal tissue from all fruits to investigate the impact of cell size on T2 value. The results showed that the MRI transverse relaxation signal is well fitted by a tri-exponential decay curve that reflects cell compartmentalization. Variations in cell size partially explained the different T2 observed. This study highlighted the heterogeneity of apple tissues in terms of relaxation parameters, apparent microporosity and cell morphology and in relation to specific variations between fruit of different cultivars.

  1. A bulk sub-femtoliter in vitro compartmentalization system using super-fine electrosprays.

    PubMed

    Sharma, Bineet; Takamura, Yuzuru; Shimoda, Tatsuya; Biyani, Manish

    2016-01-01

    The extreme miniaturization of biological and chemical assays in aqueous-droplet compartments enables spatiotemporal control for large-scale parallel experimentation and can thus permit new capabilities for "digitizing" directed molecular evolution methodologies. We report a remarkably facile bulk method to generate mega-scale monodisperse sub-femtoliter aqueous droplets by electrospray, using a prototype head with super-fine inkjet technology. Moreover, the electrostatic inkjet nozzle that injects the aqueous phase when immersed within an immiscible phase (an optimized oil/surfactant mixture) has the advantage of generating cell-like sub-femtoliter compartments for biomolecule encapsulation and successive biological and chemical reactions. Sub-femtoliter droplets of both liquid (water-in-oil, volumes ranging from 0.2 to 6.4 fL) and gel bead (agarose-in-oil, volume ranging from 0.3 to 15.6 fL) compartments with average sizes of 1.3 μm and 1.5 μm, respectively, were successfully generated using an inkjet nozzle at a speed of more than 10(5) droplets per second. We demonstrated the applicability of this system by synthesizing fluorescent proteins using a cell-free expression system inside electrosprayed sub-femtoliter droplets at an accelerated rate, thereby extending the utility of in vitro compartmentalization with improved analytical performance for a top-down artificial cellular system. PMID:27199080

  2. Photoacoustic “nanobombs” fight against undesirable vesicular compartmentalization of anticancer drugs

    PubMed Central

    Chen, Aiping; Xu, Chun; Li, Min; Zhang, Hailin; Wang, Diancheng; Xia, Mao; Meng, Gang; Kang, Bin; Chen, Hongyuan; Wei, Jiwu

    2015-01-01

    Undesirable intracellular vesicular compartmentalization of anticancer drugs in cancer cells is a common cause of chemoresistance. Strategies aimed at circumventing this problem may improve chemotherapeutic efficacy. We report a novel photophysical strategy for controlled-disruption of vesicular sequestration of the anticancer drug doxorubicin (DOX). Single-walled carbon nanotubes (SWCNTs), modified with folate, were trapped in acidic vesicles after entering lung cancer cells. Upon irradiation by near-infrared pulsed laser, these vesicles were massively broken by the resulting photoacoustic shockwave, and the vesicle-sequestered contents were released, leading to redistribution of DOX from cytoplasm to the target-containing nucleus. Redistribution resulted in 12-fold decrease of the EC50 of DOX in lung cancer cells, and enhanced antitumor efficacy of low-dose DOX in tumor-bearing mice. Side effects were not observed. These findings provide insights of using nanotechnology to improve cancer chemotherapy, i.e. not only for drug delivery, but also for overcoming intracellular drug-transport hurdles. PMID:26483341

  3. Identification of HIV-1 Genitourinary Tract Compartmentalization by Analyzing the env Gene Sequences in Urine

    PubMed Central

    BLASI, Maria; CARPENTER, J. Harris; BALAKUMARAN, Bala; CARA, Andrea; GAO, Feng; KLOTMAN, Mary E.

    2015-01-01

    Objective HIV-1 persists indefinitely in memory CD4+ T cells and other long-lived cellular reservoirs despite antiretroviral therapy (ART). Our group had previously demonstrated that HIV-1 can establish a productive infection in renal epithelial cells and that the kidney represents a separate compartment for HIV-1 replication. Here, to better understand the viruses in this unique site, we genetically characterized and compared the viruses in blood and urine specimens from twenty-four HIV-1 infected subjects with detectable viremia. Design and Methods Blood and urine samples were obtained from 35 HIV-1 positive subjects. Single-genome amplification was performed on HIV-1 env RNA and DNA isolated from urine supernatants and urine derived cell pellets respectively, as well as from plasma and PBMC from the same individuals. Neighbor-joining trees were constructed under the Kimura 2-parameter mode. Results We amplified and sequenced the full-length HIV-1 envelope (env) gene from twelve of the twenty-four individuals, indicating that fifty percent (50%) of the viremic HIV-1 positive patients had viral RNA in their urine. Phylogenetic analysis of the env sequences from four subjects with more than fifteen urine-derived env sequences showed that the majority of the sequences from urine formed distinct cluster(s) independent of those PBMC and plasma-derived sequences, consistent with viral compartmentalization in the urine. Conclusions Our results suggest the presence of a distinct HIV compartment in the genitourinary tract. PMID:26372275

  4. Local Microenvironment Controls the Compartmentalization of NK Cell Responses during Systemic Inflammation in Mice.

    PubMed

    Rasid, Orhan; Ciulean, Ioana Sonya; Fitting, Catherine; Doyen, Noelle; Cavaillon, Jean-Marc

    2016-09-15

    Systemic inflammatory response syndrome is a whole-body reaction to a triggering insult that often results in life-threatening illness. Contributing to the development of this inflammatory cascade are numerous cellular partners, among which NK cells were shown to play a key role. Accumulating evidence points to organ-specific properties of systemic inflammation and NK cells. However, little is known about compartment-specific activation of NK cells during systemic inflammatory response syndrome or the relative contribution of NK cell-intrinsic properties and microenvironmental cues. In this study, we undertook a sequential characterization of NK responses in the spleen, lungs, bone marrow, peritoneum, and blood using a mouse model of endotoxemia. We report that, despite similar systemic dynamics of NK cell responses, expression of activation markers (CD69 and CD25) and effector molecules (IFN-γ, granzyme B, and IL-10) display organ-specific thresholds of maximum activation. Using adoptive transfers of spleen and lung NK cells, we found that these cells have the capacity to quickly adapt to a new environment and adjust their response levels to that of resident NK cells. This functional adaptation occurs without significant alterations in phenotype and independently of subpopulation-specific trafficking. Thus, using a dynamic in vivo-transfer system, to our knowledge our study is the first to report the compartmentalization of NK cells responses during systemic inflammation and to show that NK cell-intrinsic properties and microenvironmental cues are involved in this process, in a sequential manner. PMID:27521338

  5. A nanoliter self-priming compartmentalization chip for point-of-care digital PCR analysis.

    PubMed

    Song, Qi; Gao, Yibo; Zhu, Qiangyuan; Tian, Qingchang; Yu, Bingwen; Song, Bofan; Xu, Yanan; Yuan, Maokai; Ma, Congcong; Jin, Wei; Zhang, Tao; Mu, Ying; Jin, Qinhan

    2015-01-01

    A nanoliter self-priming compartmentalization (SPC) microfluidic chip suited for the digital polymerase chain reaction (dPCR) analysis in point-of-care testing (POCT) has been developed. This dPCR chip is fabricated of polydimethylsiloxane (PDMS). After the dPCR chip is evacuated, there will be a negative pressure environment in the chip because of the gas solubility of PDMS. The negative pressure environment can provide a self-priming power so that the sample solutions can be sucked into each reaction chamber sequentially. The whole sampling process requires no external power and is valve-free. Channels that contain water are designed around each sample panel to prevent the solvent (water) from evaporating during dPCR process. A glass coverslip is also used as a waterproof layer, which is more convenient and more efficient than other waterproof methods seen in literature. This dPCR chip allows three samples to be amplified at the same time. Each sample is distributed into 1040 reaction chambers, and each chamber is only 2.08 nL. Human β-actin DNA solutions of known concentrations are used as the templates for the dPCR analyses to verify the sensitivity and accuracy of the method. Template DNA solutions diluted to concentrations of 300, 100 and 10 copies/μL are tested and shown that this simple, portable and self-priming dPCR chip can be used at any clinic as a real POCT technique. PMID:26022215

  6. A nanoliter self-priming compartmentalization chip for point-of-care digital PCR analysis.

    PubMed

    Song, Qi; Gao, Yibo; Zhu, Qiangyuan; Tian, Qingchang; Yu, Bingwen; Song, Bofan; Xu, Yanan; Yuan, Maokai; Ma, Congcong; Jin, Wei; Zhang, Tao; Mu, Ying; Jin, Qinhan

    2015-01-01

    A nanoliter self-priming compartmentalization (SPC) microfluidic chip suited for the digital polymerase chain reaction (dPCR) analysis in point-of-care testing (POCT) has been developed. This dPCR chip is fabricated of polydimethylsiloxane (PDMS). After the dPCR chip is evacuated, there will be a negative pressure environment in the chip because of the gas solubility of PDMS. The negative pressure environment can provide a self-priming power so that the sample solutions can be sucked into each reaction chamber sequentially. The whole sampling process requires no external power and is valve-free. Channels that contain water are designed around each sample panel to prevent the solvent (water) from evaporating during dPCR process. A glass coverslip is also used as a waterproof layer, which is more convenient and more efficient than other waterproof methods seen in literature. This dPCR chip allows three samples to be amplified at the same time. Each sample is distributed into 1040 reaction chambers, and each chamber is only 2.08 nL. Human β-actin DNA solutions of known concentrations are used as the templates for the dPCR analyses to verify the sensitivity and accuracy of the method. Template DNA solutions diluted to concentrations of 300, 100 and 10 copies/μL are tested and shown that this simple, portable and self-priming dPCR chip can be used at any clinic as a real POCT technique. PMID:26029750

  7. Dynamic dendritic compartmentalization underlies stimulus-specific adaptation in an insect neuron.

    PubMed

    Prešern, Janez; Triblehorn, Jeffrey D; Schul, Johannes

    2015-06-01

    In many neural systems, repeated stimulation leads to stimulus-specific adaptation (SSA), with responses to repeated signals being reduced while responses to novel stimuli remain unaffected. The underlying mechanisms of SSA remain mostly hypothetical. One hypothesis is that dendritic processes generate SSA. Evidence for such a mechanism was recently described in an insect auditory interneuron (TN-1 in Neoconocephalus triops). Afferents, tuned to different frequencies, connect with different parts of the TN-1 dendrite. The specific adaptation of these inputs relies on calcium and sodium accumulation within the dendrite, with calcium having a transient and sodium a tonic effect. Using imaging techniques, we tested here whether the accumulation of these ions remained limited to the stimulated parts of the dendrite. Stimulation with a fast pulse rate, which results in strong adaptation, elicited a transient dendritic calcium signal. In contrast, the sodium signal was tonic, remaining high during the fast pulse rate stimulus. These time courses followed the predictions from the previous pharmacological experiments. The peak positions of the calcium and sodium signals differed with the carrier frequency of the stimulus; at 15 kHz, peak locations were significantly more rostral than at 40 kHz. This matched the predictions made from neuroanatomical data. Our findings confirm that excitatory postsynaptic potentials rather than spiking cause the increase of dendritic calcium and sodium concentrations and that these increases remain limited to the stimulated parts of the dendrite. This supports the hypothesis of "dynamic dendritic compartmentalization" underlying SSA in this auditory interneuron. PMID:25878158

  8. Immunometabolism of obesity and diabetes: microbiota link compartmentalized immunity in the gut to metabolic tissue inflammation.

    PubMed

    McPhee, Joseph B; Schertzer, Jonathan D

    2015-12-01

    The bacteria that inhabit us have emerged as factors linking immunity and metabolism. Changes in our microbiota can modify obesity and the immune underpinnings of metabolic diseases such as Type 2 diabetes. Obesity coincides with a low-level systemic inflammation, which also manifests within metabolic tissues such as adipose tissue and liver. This metabolic inflammation can promote insulin resistance and dysglycaemia. However, the obesity and metabolic disease-related immune responses that are compartmentalized in the intestinal environment do not necessarily parallel the inflammatory status of metabolic tissues that control blood glucose. In fact, a permissive immune environment in the gut can exacerbate metabolic tissue inflammation. Unravelling these discordant immune responses in different parts of the body and establishing a connection between nutrients, immunity and the microbiota in the gut is a complex challenge. Recent evidence positions the relationship between host gut barrier function, intestinal T cell responses and specific microbes at the crossroads of obesity and inflammation in metabolic disease. A key problem to be addressed is understanding how metabolite, immune or bacterial signals from the gut are relayed and transferred into systemic or metabolic tissue inflammation that can impair insulin action preceding Type 2 diabetes.

  9. Predicting abundances of plants and pollinators using a simple compartmental mutualistic model.

    PubMed

    Fort, Hugo; Mungan, Muhittin

    2015-06-01

    Key gaps to be filled in population and community ecology are predicting the strength of species interactions and linking pattern with process to understand species coexistence and their relative abundances. In the case of mutualistic webs, like plant-pollinator networks, advances in understanding species abundances are currently limited, mainly owing to the lack of methodological tools to deal with the intrinsic complexity of mutualisms. Here, we propose an aggregation method leading to a simple compartmental mutualistic population model that captures both qualitatively and quantitatively the size-segregated populations observed in a Mediterranean community of nectar-producing plant species and nectar-searching animal species. We analyse the issue of optimal aggregation level and its connection with the trade-off between realism and overparametrization. We show that aggregation of both plants and pollinators into five size classes or compartments leads to a robust model with only two tunable parameters. Moreover, if, in each compartment, (i) the interaction coefficients fulfil the condition of weak mutualism and (ii) the mutualism is facultative for at least one party of the compartment, then the interactions between different compartments are sufficient to guarantee global stability of the equilibrium population. PMID:25948690

  10. Dissecting the Subcellular Compartmentation of Proteins and Metabolites in Arabidopsis Leaves Using Non-aqueous Fractionation *

    PubMed Central

    Arrivault, Stéphanie; Guenther, Manuela; Florian, Alexandra; Encke, Beatrice; Feil, Regina; Vosloh, Daniel; Lunn, John E.; Sulpice, Ronan; Fernie, Alisdair R.; Stitt, Mark; Schulze, Waltraud X.

    2014-01-01

    Non-aqueous fractionation is a technique for the enrichment of different subcellular compartments derived from lyophilized material. It was developed to study the subcellular distribution of metabolites. Here we analyzed the distribution of about 1,000 proteins and 70 metabolites, including 22 phosphorylated intermediates in wild-type Arabidopsis rosette leaves, using non-aqueous gradients divided into 12 fractions. Good separation of plastidial, cytosolic, and vacuolar metabolites and proteins was achieved, but cytosolic, mitochondrial, and peroxisomal proteins clustered together. There was considerable heterogeneity in the fractional distribution of transcription factors, ribosomal proteins, and subunits of the vacuolar-ATPase, indicating diverse compartmental location. Within the plastid, sub-organellar separation of thylakoids and stromal proteins was observed. Metabolites from the Calvin–Benson cycle, photorespiration, starch and sucrose synthesis, glycolysis, and the tricarboxylic acid cycle grouped with their associated proteins of the respective compartment. Non-aqueous fractionation thus proved to be a powerful method for the study of the organellar, and in some cases sub-organellar, distribution of proteins and their association with metabolites. It remains the technique of choice for the assignment of subcellular location to metabolites in intact plant tissues, and thus the technique of choice for doing combined metabolite–protein analysis on a single tissue sample. PMID:24866124

  11. Reservoir compartmentalization and management strategies: Lessons learned in the Illinois basin

    SciTech Connect

    Grube, J.P.; Crockett, J.E.; Huff, B.G.

    1997-08-01

    A research project jointly sponsored by the US Department of Energy and the Illinois State Geological Survey focused on the Cypress and Aux Vases Formations (Mississippian), major clastic reservoirs in the Illinois Basin. Results from the research showed that understanding the nature and distribution of reservoir compartments, and using effective reservoir management strategies, can significantly improve recovery efficiencies from oil fields in this mature basin. Compartments can be most effectively drained where they are geologically well defined and reservoir management practices are coordinated through unified, compartment-wide, development programs. Our studies showed that the Cypress and Aux Vases reservoirs contain lateral and vertical permeability barriers forming compartments that range in size from isolated, interlaminated sandstone and shale beds to sandstone bodies tens of feet in thickness and more than a mile in length. Stacked or shingled, genetically similar sandstone bodies are commonly separated by thin impermeable intervals that can be difficult to distinguish on logs and can, therefore, cause correlation problems, even between wells drilled on spacing of less than ten acres. Lateral separation of sandstone bodies causes similar problems. Reservoir compartmentalization reduces primary and particularly secondary recovery by trapping pockets of by-passed or banked oil. Compartments can be detected by comparing recovery factors of genetically similar sandstone bodies within a field; using packers to separate commingled intervals and analyzing fluid recoveries and pressures; making detailed core-to-log calibrations that identify compartment boundaries; and analyzing pressure data from waterflood programs.

  12. Origin and evolution of metabolic sub-cellular compartmentalization in eukaryotes

    PubMed Central

    Gabaldón, Toni; Pittis, Alexandros A.

    2015-01-01

    A high level of subcellular compartmentalization is a hallmark of eukaryotic cells. This intricate internal organization was present already in the common ancestor of all extant eukaryotes, and the determination of the origins and early evolution of the different organelles remains largely elusive. Organellar proteomes are determined through regulated pathways that target proteins produced in the cytosol to their final subcellular destinations. This internal sorting of proteins can vary across different physiological conditions, cell types and lineages. Evolutionary retargeting – the alteration of a subcellular localization of a protein in the course of evolution – has been rampant in eukaryotes and involves any possible combination of organelles. This fact adds another layer of difficulty to the reconstruction of the origins and evolution of organelles. In this review we discuss current themes in relation to the origin and evolution of organellar proteomes. Throughout the text, a special focus is set on the evolution of mitochondrial and peroxisomal proteomes, which are two organelles for which extensive proteomic and evolutionary studies have been performed. PMID:25869000

  13. Bystander effects and compartmental stress response to X-ray irradiation in L929 cells.

    PubMed

    Temelie, Mihaela; Stroe, Daniela; Petcu, Ileana; Mustaciosu, Cosmin; Moisoi, Nicoleta; Savu, Diana

    2016-08-01

    Bystander effects are indirect consequences of radiation and many other stress factors. They occur in cells that are not directly exposed to these factors, but receive signals from affected cells either by gap junctions or by molecules released in the medium. Characterizing these effects and deciphering the underlying mechanisms involved in radiation-induced bystander effects are relevant for cancer radiotherapy and radioprotection. At doses of X-ray radiation 0.5 and 1 Gy, we detected bystander effects as increased numbers of micronuclei shortly after the treatment, through medium transfer and by co-cultures. Interestingly, bystander cells did not exhibit long-term adverse changes in viability. Evaluation of several compartmental stress markers (CHOP, BiP, mtHsp60, cytHsp70) by qRT-PCR did not reveal expression changes at transcriptional level. We investigated the involvement of ROS and NO in this process by addition of specific scavengers of these molecules, DMSO or c-PTIO in the transferred medium. This approach proved that ROS but not NO is involved in the induction of lesions in the acceptor cells. These results indicate that L929 cells are susceptible to stress effects of radiation-induced bystander signaling. PMID:27025606

  14. A bulk sub-femtoliter in vitro compartmentalization system using super-fine electrosprays

    PubMed Central

    Sharma, Bineet; Takamura, Yuzuru; Shimoda, Tatsuya; Biyani, Manish

    2016-01-01

    The extreme miniaturization of biological and chemical assays in aqueous-droplet compartments enables spatiotemporal control for large-scale parallel experimentation and can thus permit new capabilities for “digitizing” directed molecular evolution methodologies. We report a remarkably facile bulk method to generate mega-scale monodisperse sub-femtoliter aqueous droplets by electrospray, using a prototype head with super-fine inkjet technology. Moreover, the electrostatic inkjet nozzle that injects the aqueous phase when immersed within an immiscible phase (an optimized oil/surfactant mixture) has the advantage of generating cell-like sub-femtoliter compartments for biomolecule encapsulation and successive biological and chemical reactions. Sub-femtoliter droplets of both liquid (water-in-oil, volumes ranging from 0.2 to 6.4 fL) and gel bead (agarose-in-oil, volume ranging from 0.3 to 15.6 fL) compartments with average sizes of 1.3 μm and 1.5 μm, respectively, were successfully generated using an inkjet nozzle at a speed of more than 105 droplets per second. We demonstrated the applicability of this system by synthesizing fluorescent proteins using a cell-free expression system inside electrosprayed sub-femtoliter droplets at an accelerated rate, thereby extending the utility of in vitro compartmentalization with improved analytical performance for a top-down artificial cellular system. PMID:27199080

  15. Modeling Heterogeneity in Direct Infectious Disease Transmission in a Compartmental Model.

    PubMed

    Kong, Lingcai; Wang, Jinfeng; Han, Weiguo; Cao, Zhidong

    2016-03-01

    Mathematical models have been used to understand the transmission dynamics of infectious diseases and to assess the impact of intervention strategies. Traditional mathematical models usually assume a homogeneous mixing in the population, which is rarely the case in reality. Here, we construct a new transmission function by using as the probability density function a negative binomial distribution, and we develop a compartmental model using it to model the heterogeneity of contact rates in the population. We explore the transmission dynamics of the developed model using numerical simulations with different parameter settings, which characterize different levels of heterogeneity. The results show that when the reproductive number, R₀, is larger than one, a low level of heterogeneity results in dynamics similar to those predicted by the homogeneous mixing model. As the level of heterogeneity increases, the dynamics become more different. As a test case, we calibrated the model with the case incidence data for severe acute respiratory syndrome (SARS) in Beijing in 2003, and the estimated parameters demonstrated the effectiveness of the control measures taken during that period. PMID:26927140

  16. Proposing a Compartmental Model for Leprosy and Parameterizing Using Regional Incidence in Brazil

    PubMed Central

    2016-01-01

    Hansen’s disease (HD), or leprosy, is still considered a public health risk in much of Brazil. Understanding the dynamics of the infection at a regional level can aid in identification of targets to improve control. A compartmental continuous-time model for leprosy dynamics was designed based on understanding of the biology of the infection. The transmission coefficients for the model and the rate of detection were fit for each region using Approximate Bayesian Computation applied to paucibacillary and multibacillary incidence data over the period of 2000 to 2010, and model fit was validated on incidence data from 2011 to 2012. Regional variation was noted in detection rate, with cases in the Midwest estimated to be infectious for 10 years prior to detection compared to 5 years for most other regions. Posterior predictions for the model estimated that elimination of leprosy as a public health risk would require, on average, 44–45 years in the three regions with the highest prevalence. The model is easily adaptable to other settings, and can be studied to determine the efficacy of improved case finding on leprosy control. PMID:27532862

  17. Predicting abundances of plants and pollinators using a simple compartmental mutualistic model

    PubMed Central

    Fort, Hugo; Mungan, Muhittin

    2015-01-01

    Key gaps to be filled in population and community ecology are predicting the strength of species interactions and linking pattern with process to understand species coexistence and their relative abundances. In the case of mutualistic webs, like plant–pollinator networks, advances in understanding species abundances are currently limited, mainly owing to the lack of methodological tools to deal with the intrinsic complexity of mutualisms. Here, we propose an aggregation method leading to a simple compartmental mutualistic population model that captures both qualitatively and quantitatively the size-segregated populations observed in a Mediterranean community of nectar-producing plant species and nectar-searching animal species. We analyse the issue of optimal aggregation level and its connection with the trade-off between realism and overparametrization. We show that aggregation of both plants and pollinators into five size classes or compartments leads to a robust model with only two tunable parameters. Moreover, if, in each compartment, (i) the interaction coefficients fulfil the condition of weak mutualism and (ii) the mutualism is facultative for at least one party of the compartment, then the interactions between different compartments are sufficient to guarantee global stability of the equilibrium population. PMID:25948690

  18. Compartmental analysis of technetium-99m-teboroxime kinetics employing fast dynamic SPECT at rest and stress

    SciTech Connect

    Chiao, P.C.; Ficaro, E.P.; Dayaniki, F.

    1994-08-01

    The authors have examined the feasibility of compartmental analysis of {sup 99m}Tc-teboroxime kinetics in measuring physiological changes in response to adenosine-induced coronary vasodilation. To evaluate the effect of tracer recirculation on {sup 99m}Tc-teboroxime kinetics in the myocardium, they also compared compartmental analysis with washout analysis (monoexponertial fitting), which does not account for this effect. Eight healthy male volunteers were imaged using fast dynamic SPECT protocols (5 sec per tomographic image) at rest and during adenosine infusion. A two-compartment model was used and compartmental parameters K1 and k2 (characterizing the diffusion of {sup 99m}Tc-teboroxime from the blood to the myocardium and from the myocardium to the blood, respectively) were fitted from myocardial time-activity curves and left ventricular input functions. Both K1 and washout estimates for the whole left ventricular myocardium changed significantly in response to coronary vasodilation. Mean stress-to-rest (S/R) ratios were almost two times higher for K1 (S/R = 2.7 {plus_minus} 1.1) than for washout estimates (S/R = 1.5 {plus_minus} 0.3). Estimation of K1 for all local regions, except the septal wall, is feasible because variations in K1 estimates for all local regions, except the septum during stress, are comparable with those for the global region. The authors conclude that quantitative compartmental analysis of {sup 99m}Tc-teboroxime kinetics provides a sensitive indicator for changes in response to adenosine-induced coronary vasodilation. 39 refs., 7 figs., 1 tab.

  19. Unchanged mitochondrial organization and compartmentation of high-energy phosphates in creatine-deficient GAMT−/− mouse hearts

    PubMed Central

    Branovets, Jelena; Sepp, Mervi; Kotlyarova, Svetlana; Jepihhina, Natalja; Sokolova, Niina; Aksentijevic, Dunja; Lygate, Craig A.; Neubauer, Stefan; Birkedal, Rikke

    2013-01-01

    Disruption of the creatine kinase (CK) system in hearts of CK-deficient mice leads to changes in the ultrastructure and regulation of mitochondrial respiration. We expected to see similar changes in creatine-deficient mice, which lack the enzyme guanidinoacetate methyltransferase (GAMT) to produce creatine. The aim of this study was to characterize the changes in cardiomyocyte mitochondrial organization, regulation of respiration, and intracellular compartmentation associated with GAMT deficiency. Three-dimensional mitochondrial organization was assessed by confocal microscopy. On populations of permeabilized cardiomyocytes, we recorded ADP and ATP kinetics of respiration, competition between mitochondria and pyruvate kinase for ADP produced by ATPases, ADP kinetics of endogenous pyruvate kinase, and ATP kinetics of ATPases. These data were analyzed by mathematical models to estimate intracellular compartmentation. Quantitative analysis of morphological and kinetic data as well as derived model fits showed no difference between GAMT-deficient and wild-type mice. We conclude that inactivation of the CK system by GAMT deficiency does not alter mitochondrial organization and intracellular compartmentation in relaxed cardiomyocytes. Thus, our results suggest that the healthy heart is able to preserve cardiac function at a basal level in the absence of CK-facilitated energy transfer without compromising intracellular organization and the regulation of mitochondrial energy homeostasis. This raises questions on the importance of the CK system as a spatial energy buffer in unstressed cardiomyocytes. PMID:23792673

  20. Unchanged mitochondrial organization and compartmentation of high-energy phosphates in creatine-deficient GAMT-/- mouse hearts.

    PubMed

    Branovets, Jelena; Sepp, Mervi; Kotlyarova, Svetlana; Jepihhina, Natalja; Sokolova, Niina; Aksentijevic, Dunja; Lygate, Craig A; Neubauer, Stefan; Vendelin, Marko; Birkedal, Rikke

    2013-08-15

    Disruption of the creatine kinase (CK) system in hearts of CK-deficient mice leads to changes in the ultrastructure and regulation of mitochondrial respiration. We expected to see similar changes in creatine-deficient mice, which lack the enzyme guanidinoacetate methyltransferase (GAMT) to produce creatine. The aim of this study was to characterize the changes in cardiomyocyte mitochondrial organization, regulation of respiration, and intracellular compartmentation associated with GAMT deficiency. Three-dimensional mitochondrial organization was assessed by confocal microscopy. On populations of permeabilized cardiomyocytes, we recorded ADP and ATP kinetics of respiration, competition between mitochondria and pyruvate kinase for ADP produced by ATPases, ADP kinetics of endogenous pyruvate kinase, and ATP kinetics of ATPases. These data were analyzed by mathematical models to estimate intracellular compartmentation. Quantitative analysis of morphological and kinetic data as well as derived model fits showed no difference between GAMT-deficient and wild-type mice. We conclude that inactivation of the CK system by GAMT deficiency does not alter mitochondrial organization and intracellular compartmentation in relaxed cardiomyocytes. Thus, our results suggest that the healthy heart is able to preserve cardiac function at a basal level in the absence of CK-facilitated energy transfer without compromising intracellular organization and the regulation of mitochondrial energy homeostasis. This raises questions on the importance of the CK system as a spatial energy buffer in unstressed cardiomyocytes. PMID:23792673

  1. Stem cell compartmentalization in diabetes and high cardiovascular risk reveals the role of DPP-4 in diabetic stem cell mobilopathy.

    PubMed

    Fadini, Gian Paolo; Albiero, Mattia; Seeger, Florian; Poncina, Nicol; Menegazzo, Lisa; Angelini, Annalisa; Castellani, Chiara; Thiene, Gaetano; Agostini, Carlo; Cappellari, Roberta; Boscaro, Elisa; Zeiher, Andreas; Dimmeler, Stefanie; Avogaro, Angelo

    2013-01-01

    Bone marrow (BM) derived stem and progenitor cells contribute to cardiovascular homeostasis and are affected by cardiovascular risk factors. We devised a clinical data-driven approach to test candidate stem cell mobilizing mechanisms in pre-clinical models. We found that PB and BM CD34+ cell counts were directly correlated, and that most circulating CD34+ cells were viable, non-proliferating and derived from the BM. Thus, we analyzed PB and BM CD34+ cell levels as a two-compartment model in 72 patients with or without cardiovascular disease. Self-organizing maps showed that disturbed compartmentalization of CD34+ cells was associated with aging and cardiovascular risk factors especially diabetes. High activity of DPP-4, a regulator of the mobilizing chemokine SDF-1α, was associated with altered stem cell compartmentalization. For validation of these findings, we assessed the role of DPP-4 in the BM mobilization response of diabetic rats. Diabetes differentially affected DPP-4 activity in PB and BM and impaired stem/progenitor cell mobilization after ischemia or G-CSF administration. DPP-4 activity in the BM was required for the mobilizing effect of G-CSF, while in PB it blunted ischemia-induced mobilization. Indeed, DPP-4 deficiency restored ischemia (but not G-CSF)-induced stem cell mobilization and improved vascular recovery in diabetic animals. In conclusion, the analysis of stem cell compartmentalization in humans led us to discover mechanisms of BM unresponsiveness in diabetes determined by tissue-specific DPP-4 dysregulation.

  2. Using pressure transient analysis to improve well performance and optimize field development in compartmentalized shelf margin deltaic reservoirs

    SciTech Connect

    Badgett, K.L.; Crawford, G.E.; Mills, W.H.

    1996-12-31

    BP Exploration`s Gulf of Mexico group developed procedures to conduct effective well tests on conventional production wells and employed them during the development drilling phase of the Mississippi Canyon 109 (MC109) field. Bottomhole pressure data were recorded during the initial few weeks of production. Typically, a 48 hour pressure buildup survey (surface shut-in) was obtained near the end of data acquisition. Data from these tests were analyzed for completion efficiency, reservoir flow capacity, reservoir heterogeneities, and drainage area. Initially wells were gravel packed for sand control, until buildup interpretations indicated skins greater than 20. Frac packing technology was then employed, and an immediate improvement was observed with skins dropping into the teens. Over a period of time frac packs were optimized using the test derived skins as a metric. Analysis of pressure data also played an important role in identifying reservoir compartmentalization. The two major reservoir horizons at MC 109 are interpreted as shelf margin deltas. However, each of these has distinctly different compartmentalization issues. The continuous character of the G Sand made it easier to define the depositional system and investigate reservoir compartmentalization issues using a combination of well log, 3D seismic, static pressure trends, and fluid information. In the more distal deltaic reservoirs of the J Sand however, complications with seismic amplitudes and a less reliable tie between wireline and seismic data required the use of pressure transient analysis to efficiently exploit the reservoir.

  3. A Crowdsourced nucleus: Understanding nuclear organization in terms of dynamically networked protein function

    PubMed Central

    Wood, Ashley M.; Garza-Gongora, Arturo G.; Kosak, Steven T.

    2014-01-01

    The spatial organization of the nucleus results in a compartmentalized structure that affects all aspects of nuclear function. This compartmentalization involves genome organization as well as the formation of nuclear bodies and plays a role in many functions, including gene regulation, genome stability, replication, and RNA processing. Here we review the recent findings associated with the spatial organization of the nucleus and reveal that a common theme for nuclear proteins is their ability to participate in a variety of functions and pathways. We consider this multiplicity of function in terms of Crowdsourcing, a recent phenomenon in the world of information technology, and suggest that this model provides a novel way to synthesize the many intersections between nuclear organization and function. PMID:24412853

  4. Retinol metabolism in rats with low vitamin A status: A compartmental model

    SciTech Connect

    Lewis, K.C.; Green, M.H.; Green, J.B.; Zech, L.A. )

    1990-09-01

    A compartmental model was developed to describe the metabolism of vitamin A in rats with low vitamin A status maintained by a low dietary intake of vitamin A (approximately 2 micrograms retinol equivalents/day). After the IV bolus injection of (3H)retinol in its physiological transport complex, tracer and trace data were obtained from plasma, organs (liver, kidneys, small intestine, eyes, adrenals, testes, lungs, carcass), and tracer data were obtained from urine and feces. The dietary protocol developed for this study resulted in animals having plasma vitamin A levels less than 10 micrograms retinol/dl and total liver vitamin A levels of approximately 1 microgram retinol equivalent. Four compartments were used to model the plasma: one to describe retinol, one to describe the nonphysiological portion of the dose, and two to simulate polar metabolites derived from retinol. The liver required two compartments and a delay, the carcass (small intestine, eyes, adrenals, testes, and lungs, plus remaining carcass) required three compartments, and the kidneys required two. The model predicted a vitamin A utilization rate of 1.65 micrograms retinol equivalents/day with the urine and feces accounting for most of the output. The plasma retinol turnover rate was approximately 20 micrograms retinol equivalents/day; this was 12 times greater than the utilization rate. This indicated that, of the large amount of retinol moving through the plasma each day, less than 10% of this was actually being irreversibly utilized. Similarly, as compared to the whole-body utilization rate, there was a relatively high turnover rate of retinol in the kidneys, carcass, and liver, coupled with a high degree of recycling of vitamin A through these tissues. Of the total vitamin A that entered the liver from all sources including the diet, approximately 86% was mobilized into the plasma.

  5. Application of oil gas-chromatography in reservoir compartmentalization in a mature Venezuelan oil field

    SciTech Connect

    Munoz, N.G.; Mompart, L.; Talukdar, S.C.

    1996-08-01

    Gas chromatographic oil {open_quotes}fingerprinting{close_quotes} was successfully applied in a multidisciplinary production geology project by Maraven, S.A. to define the extent of vertical and lateral continuity of Eocene and Miocene sandstone reservoirs in the highly faulted Bloque I field, Maracaibo Basin, Venezuela. Seventy-five non-biodegraded oils (20{degrees}-37.4{degrees} API) were analyzed with gas chromatography. Fifty were produced from the Eocene Misoa C-4, C-5, C-6 or C-7 horizons, fifteen from the Miocene basal La Rosa and ten from multizone completions. Gas chromatographic and terpane and sterane biomarker data show that all of the oils are genetically related. They were expelled from a type II, Upper Cretaceous marine La Luna source rock at about 0.80-0.90% R{sub o} maturity. Alteration in the reservoir by gas stripping with or without subsequent light hydrocarbons mixing was observed in some oils. Detailed chromatographic comparisons among the oils shown by star plots and cluster analysis utilizing several naphthenic and aromatic peak height ratios, resulted in oil pool groupings. This led to finding previously unknown lateral and vertical reservoir communication and also helped in checking and updating the scaling character of faults. In the commingled oils, percentages of each contributing zone in the mixture were also determined giving Maraven engineers a proven, rapid and inexpensive tool for production allocation and reservoir management The oil pool compartmentalization defined by the geochemical fingerprinting is in very good agreement with the sequence stratigraphic interpretation of the reservoirs and helped evaluate the influence of structure in oil migration and trapping.

  6. Compartmentalized cyanophycin metabolism in the diazotrophic filaments of a heterocyst-forming cyanobacterium.

    PubMed

    Burnat, Mireia; Herrero, Antonia; Flores, Enrique

    2014-03-11

    Heterocyst-forming cyanobacteria are multicellular organisms in which growth requires the activity of two metabolically interdependent cell types, the vegetative cells that perform oxygenic photosynthesis and the dinitrogen-fixing heterocysts. Vegetative cells provide the heterocysts with reduced carbon, and heterocysts provide the vegetative cells with fixed nitrogen. Heterocysts conspicuously accumulate polar granules made of cyanophycin [multi-L-arginyl-poly (L-aspartic acid)], which is synthesized by cyanophycin synthetase and degraded by the concerted action of cyanophycinase (that releases β-aspartyl-arginine) and isoaspartyl dipeptidase (that produces aspartate and arginine). Cyanophycin synthetase and cyanophycinase are present at high levels in the heterocysts. Here we created a deletion mutant of gene all3922 encoding isoaspartyl dipeptidase in the model heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120. The mutant accumulated cyanophycin and β-aspartyl-arginine, and was impaired specifically in diazotrophic growth. Analysis of an Anabaena strain bearing an All3922-GFP (green fluorescent protein) fusion and determination of the enzyme activity in specific cell types showed that isoaspartyl dipeptidase is present at significantly lower levels in heterocysts than in vegetative cells. Consistently, isolated heterocysts released substantial amounts of β-aspartyl-arginine. These observations imply that β-aspartyl-arginine produced from cyanophycin in the heterocysts is transferred intercellularly to be hydrolyzed, producing aspartate and arginine in the vegetative cells. Our results showing compartmentalized metabolism of cyanophycin identify the nitrogen-rich molecule β-aspartyl-arginine as a nitrogen vehicle in the unique multicellular system represented by the heterocyst-forming cyanobacteria.

  7. Compartmentalized microbial composition, oxygen gradients and nitrogen fixation in the gut of Odontotaenius disjunctus

    PubMed Central

    Ceja-Navarro, Javier A; Nguyen, Nhu H; Karaoz, Ulas; Gross, Stephanie R; Herman, Donald J; Andersen, Gary L; Bruns, Thomas D; Pett-Ridge, Jennifer; Blackwell, Meredith; Brodie, Eoin L

    2014-01-01

    Coarse woody debris is an important biomass pool in forest ecosystems that numerous groups of insects have evolved to take advantage of. These insects are ecologically important and represent useful natural analogs for biomass to biofuel conversion. Using a range of molecular approaches combined with microelectrode measurements of oxygen, we have characterized the gut microbiome and physiology of Odontotaenius disjunctus, a wood-feeding beetle native to the eastern United States. We hypothesized that morphological and physiological differences among gut regions would correspond to distinct microbial populations and activities. In fact, significantly different communities were found in the foregut (FG), midgut (MG)/posterior hindgut (PHG) and anterior hindgut (AHG), with Actinobacteria and Rhizobiales being more abundant toward the FG and PHG. Conversely, fermentative bacteria such as Bacteroidetes and Clostridia were more abundant in the AHG, and also the sole region where methanogenic Archaea were detected. Although each gut region possessed an anaerobic core, micron-scale profiling identified radial gradients in oxygen concentration in all regions. Nitrogen fixation was confirmed by 15N2 incorporation, and nitrogenase gene (nifH) expression was greatest in the AHG. Phylogenetic analysis of nifH identified the most abundant transcript as related to Ni–Fe nitrogenase of a Bacteroidetes species, Paludibacter propionicigenes. Overall, we demonstrate not only a compartmentalized microbiome in this beetle digestive tract but also sharp oxygen gradients that may permit aerobic and anaerobic metabolism to occur within the same regions in close proximity. We provide evidence for the microbial fixation of N2 that is important for this beetle to subsist on woody biomass. PMID:23985746

  8. Compartmentalized cyanophycin metabolism in the diazotrophic filaments of a heterocyst-forming cyanobacterium

    PubMed Central

    Burnat, Mireia; Herrero, Antonia; Flores, Enrique

    2014-01-01

    Heterocyst-forming cyanobacteria are multicellular organisms in which growth requires the activity of two metabolically interdependent cell types, the vegetative cells that perform oxygenic photosynthesis and the dinitrogen-fixing heterocysts. Vegetative cells provide the heterocysts with reduced carbon, and heterocysts provide the vegetative cells with fixed nitrogen. Heterocysts conspicuously accumulate polar granules made of cyanophycin [multi-L-arginyl-poly (L-aspartic acid)], which is synthesized by cyanophycin synthetase and degraded by the concerted action of cyanophycinase (that releases β-aspartyl-arginine) and isoaspartyl dipeptidase (that produces aspartate and arginine). Cyanophycin synthetase and cyanophycinase are present at high levels in the heterocysts. Here we created a deletion mutant of gene all3922 encoding isoaspartyl dipeptidase in the model heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120. The mutant accumulated cyanophycin and β-aspartyl-arginine, and was impaired specifically in diazotrophic growth. Analysis of an Anabaena strain bearing an All3922-GFP (green fluorescent protein) fusion and determination of the enzyme activity in specific cell types showed that isoaspartyl dipeptidase is present at significantly lower levels in heterocysts than in vegetative cells. Consistently, isolated heterocysts released substantial amounts of β-aspartyl-arginine. These observations imply that β-aspartyl-arginine produced from cyanophycin in the heterocysts is transferred intercellularly to be hydrolyzed, producing aspartate and arginine in the vegetative cells. Our results showing compartmentalized metabolism of cyanophycin identify the nitrogen-rich molecule β-aspartyl-arginine as a nitrogen vehicle in the unique multicellular system represented by the heterocyst-forming cyanobacteria. PMID:24550502

  9. Convex-Optimization-Based Compartmental Pharmacokinetic Analysis for Prostate Tumor Characterization Using DCE-MRI.

    PubMed

    Ambikapathi, ArulMurugan; Chan, Tsung-Han; Lin, Chia-Hsiang; Yang, Fei-Shih; Chi, Chong-Yung; Wang, Yue

    2016-04-01

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a powerful imaging modality to study the pharmacokinetics in a suspected cancer/tumor tissue. The pharmacokinetic (PK) analysis of prostate cancer includes the estimation of time activity curves (TACs), and thereby, the corresponding kinetic parameters (KPs), and plays a pivotal role in diagnosis and prognosis of prostate cancer. In this paper, we endeavor to develop a blind source separation algorithm, namely convex-optimization-based KPs estimation (COKE) algorithm for PK analysis based on compartmental modeling of DCE-MRI data, for effective prostate tumor detection and its quantification. The COKE algorithm first identifies the best three representative pixels in the DCE-MRI data, corresponding to the plasma, fast-flow, and slow-flow TACs, respectively. The estimation accuracy of the flux rate constants (FRCs) of the fast-flow and slow-flow TACs directly affects the estimation accuracy of the KPs that provide the cancer and normal tissue distribution maps in the prostate region. The COKE algorithm wisely exploits the matrix structure (Toeplitz, lower triangular, and exponential decay) of the original nonconvex FRCs estimation problem, and reformulates it into two convex optimization problems that can reliably estimate the FRCs. After estimation of the FRCs, the KPs can be effectively estimated by solving a pixel-wise constrained curve-fitting (convex) problem. Simulation results demonstrate the efficacy of the proposed COKE algorithm. The COKE algorithm is also evaluated with DCE-MRI data of four different patients with prostate cancer and the obtained results are consistent with clinical observations. PMID:26292336

  10. Convex-Optimization-Based Compartmental Pharmacokinetic Analysis for Prostate Tumor Characterization Using DCE-MRI.

    PubMed

    Ambikapathi, ArulMurugan; Chan, Tsung-Han; Lin, Chia-Hsiang; Yang, Fei-Shih; Chi, Chong-Yung; Wang, Yue

    2016-04-01

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a powerful imaging modality to study the pharmacokinetics in a suspected cancer/tumor tissue. The pharmacokinetic (PK) analysis of prostate cancer includes the estimation of time activity curves (TACs), and thereby, the corresponding kinetic parameters (KPs), and plays a pivotal role in diagnosis and prognosis of prostate cancer. In this paper, we endeavor to develop a blind source separation algorithm, namely convex-optimization-based KPs estimation (COKE) algorithm for PK analysis based on compartmental modeling of DCE-MRI data, for effective prostate tumor detection and its quantification. The COKE algorithm first identifies the best three representative pixels in the DCE-MRI data, corresponding to the plasma, fast-flow, and slow-flow TACs, respectively. The estimation accuracy of the flux rate constants (FRCs) of the fast-flow and slow-flow TACs directly affects the estimation accuracy of the KPs that provide the cancer and normal tissue distribution maps in the prostate region. The COKE algorithm wisely exploits the matrix structure (Toeplitz, lower triangular, and exponential decay) of the original nonconvex FRCs estimation problem, and reformulates it into two convex optimization problems that can reliably estimate the FRCs. After estimation of the FRCs, the KPs can be effectively estimated by solving a pixel-wise constrained curve-fitting (convex) problem. Simulation results demonstrate the efficacy of the proposed COKE algorithm. The COKE algorithm is also evaluated with DCE-MRI data of four different patients with prostate cancer and the obtained results are consistent with clinical observations.

  11. Compartmentation of the cerebellar cortex: adaptation to lifestyle in the star-nosed mole Condylura cristata.

    PubMed

    Marzban, Hassan; Hoy, Nathan; Buchok, Matthew; Catania, Kenneth C; Hawkes, Richard

    2015-04-01

    The adult mammalian cerebellum is histologically uniform. However, concealed beneath the simple laminar architecture, it is organized rostrocaudally and mediolaterally into complex arrays of transverse zones and parasagittal stripes that is both highly reproducible between individuals and generally conserved across mammals and birds. Beyond this conservation, the general architecture appears to be adapted to the animal's way of life. To test this hypothesis, we have examined cerebellar compartmentation in the talpid star-nosed mole Condylura cristata. The star-nosed mole leads a subterranean life. It is largely blind and instead uses an array of fleshy appendages (the "star") to navigate and locate its prey. The hypothesis suggests that cerebellar architecture would be modified to reduce regions receiving visual input and expand those that receive trigeminal afferents from the star. Zebrin II and phospholipase Cß4 (PLCß4) immunocytochemistry was used to map the zone-and-stripe architecture of the cerebellum of the adult star-nosed mole. The general zone-and-stripe architecture characteristic of all mammals is present in the star-nosed mole. In the vermis, the four typical transverse zones are present, two with alternating zebrin II/PLCß4 stripes, two wholly zebrin II+/PLCß4-. However, the central and nodular zones (prominent visual receiving areas) are proportionally reduced in size and conversely, the trigeminal-receiving areas (the posterior zone of the vermis and crus I/II of the hemispheres) are uncharacteristically large. We therefore conclude that cerebellar architecture is generally conserved across the Mammalia but adapted to the specific lifestyle of the species.

  12. Synapse-specific compartmentalization of signaling cascades for LTP induction in CA3 interneurons.

    PubMed

    Galván, E J; Pérez-Rosello, T; Gómez-Lira, G; Lara, E; Gutiérrez, R; Barrionuevo, G

    2015-04-01

    Inhibitory interneurons with somata in strata radiatum and lacunosum-molecular (SR/L-M) of hippocampal area CA3 receive excitatory input from pyramidal cells via the recurrent collaterals (RCs), and the dentate gyrus granule cells via the mossy fibers (MFs). Here we demonstrate that Hebbian long-term potentiation (LTP) at RC synapses on SR/L-M interneurons requires the concomitant activation of calcium-impermeable AMPARs (CI-AMPARs) and N-methyl-d-aspartate receptors (NMDARs). RC LTP was prevented by voltage clamping the postsynaptic cell during high-frequency stimulation (HFS; 3 trains of 100 pulses delivered at 100 Hz every 10s), with intracellular injections of the Ca(2+) chelator BAPTA (20mM), and with the NMDAR antagonist D-AP5. In separate experiments, RC and MF inputs converging onto the same interneuron were sequentially activated. We found that RC LTP induction was blocked by inhibitors of the calcium/calmodulin-dependent protein kinase II (CaMKII; KN-62, 10 μM or KN-93, 10 μM) but MF LTP was CaMKII independent. Conversely, the application of the protein kinase A (PKA) activators forskolin/IBMX (50 μM/25 μM) potentiated MF EPSPs but not RC EPSPs. Together these data indicate that the aspiny dendrites of SR/L-M interneurons compartmentalize synapse-specific Ca(2+) signaling required for LTP induction at RC and MF synapses. We also show that the two signal transduction cascades converge to activate a common effector, protein kinase C (PKC). Specifically, LTP at RC and MF synapses on the same SR/LM interneuron was blocked by postsynaptic injections of chelerythrine (10 μM). These data indicate that both forms of LTP share a common mechanism involving PKC-dependent signaling modulation. PMID:25637803

  13. Ultrafast Diffusion of a Fluorescent Cholesterol Analog in Compartmentalized Plasma Membranes

    PubMed Central

    Hiramoto-Yamaki, Nao; Tanaka, Kenji A K; Suzuki, Kenichi G N; Hirosawa, Koichiro M; Miyahara, Manami S H; Kalay, Ziya; Tanaka, Koichiro; Kasai, Rinshi S; Kusumi, Akihiro; Fujiwara, Takahiro K

    2014-01-01

    Cholesterol distribution and dynamics in the plasma membrane (PM) are poorly understood. The recent development of Bodipy488-conjugated cholesterol molecule (Bdp-Chol) allowed us to study cholesterol behavior in the PM, using single fluorescent-molecule imaging. Surprisingly, in the intact PM, Bdp-Chol diffused at the fastest rate ever found for any molecules in the PM, with a median diffusion coefficient (D) of 3.4 µm2/second, which was ∼10 times greater than that of non-raft phospholipid molecules (0.33 µm2/second), despite Bdp-Chol's probable association with raft domains. Furthermore, Bdp-Chol exhibited no sign of entrapment in time scales longer than 0.5 milliseconds. In the blebbed PM, where actin filaments were largely depleted, Bdp-Chol and Cy3-conjugated dioleoylphosphatidylethanolamine (Cy3-DOPE) diffused at comparable Ds (medians = 5.8 and 6.2 µm2/second, respectively), indicating that the actin-based membrane skeleton reduces the D of Bdp-Chol only by a factor of ∼2 from that in the blebbed PM, whereas it reduces the D of Cy3-DOPE by a factor of ∼20. These results are consistent with the previously proposed model, in which the PM is compartmentalized by the actin-based membrane-skeleton fence and its associated transmembrane picket proteins for the macroscopic diffusion of all of the membrane molecules, and suggest that the probability of Bdp-Chol passing through the compartment boundaries, once it enters the boundary, is ∼10× greater than that of Cy3-DOPE. Since the compartment sizes are greater than those of the putative raft domains, we conclude that raft domains coexist with membrane-skeleton-induced compartments and are contained within them. PMID:24506328

  14. Compartmentalized microbial composition, oxygen gradients and nitrogen fixation in the gut of Odontotaenius disjunctus.

    PubMed

    Ceja-Navarro, Javier A; Nguyen, Nhu H; Karaoz, Ulas; Gross, Stephanie R; Herman, Donald J; Andersen, Gary L; Bruns, Thomas D; Pett-Ridge, Jennifer; Blackwell, Meredith; Brodie, Eoin L

    2014-01-01

    Coarse woody debris is an important biomass pool in forest ecosystems that numerous groups of insects have evolved to take advantage of. These insects are ecologically important and represent useful natural analogs for biomass to biofuel conversion. Using a range of molecular approaches combined with microelectrode measurements of oxygen, we have characterized the gut microbiome and physiology of Odontotaenius disjunctus, a wood-feeding beetle native to the eastern United States. We hypothesized that morphological and physiological differences among gut regions would correspond to distinct microbial populations and activities. In fact, significantly different communities were found in the foregut (FG), midgut (MG)/posterior hindgut (PHG) and anterior hindgut (AHG), with Actinobacteria and Rhizobiales being more abundant toward the FG and PHG. Conversely, fermentative bacteria such as Bacteroidetes and Clostridia were more abundant in the AHG, and also the sole region where methanogenic Archaea were detected. Although each gut region possessed an anaerobic core, micron-scale profiling identified radial gradients in oxygen concentration in all regions. Nitrogen fixation was confirmed by (15)N2 incorporation, and nitrogenase gene (nifH) expression was greatest in the AHG. Phylogenetic analysis of nifH identified the most abundant transcript as related to Ni-Fe nitrogenase of a Bacteroidetes species, Paludibacter propionicigenes. Overall, we demonstrate not only a compartmentalized microbiome in this beetle digestive tract but also sharp oxygen gradients that may permit aerobic and anaerobic metabolism to occur within the same regions in close proximity. We provide evidence for the microbial fixation of N2 that is important for this beetle to subsist on woody biomass. PMID:23985746

  15. Compartmentalized cyanophycin metabolism in the diazotrophic filaments of a heterocyst-forming cyanobacterium.

    PubMed

    Burnat, Mireia; Herrero, Antonia; Flores, Enrique

    2014-03-11

    Heterocyst-forming cyanobacteria are multicellular organisms in which growth requires the activity of two metabolically interdependent cell types, the vegetative cells that perform oxygenic photosynthesis and the dinitrogen-fixing heterocysts. Vegetative cells provide the heterocysts with reduced carbon, and heterocysts provide the vegetative cells with fixed nitrogen. Heterocysts conspicuously accumulate polar granules made of cyanophycin [multi-L-arginyl-poly (L-aspartic acid)], which is synthesized by cyanophycin synthetase and degraded by the concerted action of cyanophycinase (that releases β-aspartyl-arginine) and isoaspartyl dipeptidase (that produces aspartate and arginine). Cyanophycin synthetase and cyanophycinase are present at high levels in the heterocysts. Here we created a deletion mutant of gene all3922 encoding isoaspartyl dipeptidase in the model heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120. The mutant accumulated cyanophycin and β-aspartyl-arginine, and was impaired specifically in diazotrophic growth. Analysis of an Anabaena strain bearing an All3922-GFP (green fluorescent protein) fusion and determination of the enzyme activity in specific cell types showed that isoaspartyl dipeptidase is present at significantly lower levels in heterocysts than in vegetative cells. Consistently, isolated heterocysts released substantial amounts of β-aspartyl-arginine. These observations imply that β-aspartyl-arginine produced from cyanophycin in the heterocysts is transferred intercellularly to be hydrolyzed, producing aspartate and arginine in the vegetative cells. Our results showing compartmentalized metabolism of cyanophycin identify the nitrogen-rich molecule β-aspartyl-arginine as a nitrogen vehicle in the unique multicellular system represented by the heterocyst-forming cyanobacteria. PMID:24550502

  16. Action potential processing in a detailed Purkinje cell model reveals a critical role for axonal compartmentalization

    PubMed Central

    Masoli, Stefano; Solinas, Sergio; D'Angelo, Egidio

    2015-01-01

    The Purkinje cell (PC) is among the most complex neurons in the brain and plays a critical role for cerebellar functioning. PCs operate as fast pacemakers modulated by synaptic inputs but can switch from simple spikes to complex bursts and, in some conditions, show bistability. In contrast to original works emphasizing dendritic Ca-dependent mechanisms, recent experiments have supported a primary role for axonal Na-dependent processing, which could effectively regulate spike generation and transmission to deep cerebellar nuclei (DCN). In order to account for the numerous ionic mechanisms involved (at present including Nav1.6, Cav2.1, Cav3.1, Cav3.2, Cav3.3, Kv1.1, Kv1.5, Kv3.3, Kv3.4, Kv4.3, KCa1.1, KCa2.2, KCa3.1, Kir2.x, HCN1), we have elaborated a multicompartmental model incorporating available knowledge on localization and gating of PC ionic channels. The axon, including initial segment (AIS) and Ranvier nodes (RNs), proved critical to obtain appropriate pacemaking and firing frequency modulation. Simple spikes initiated in the AIS and protracted discharges were stabilized in the soma through Na-dependent mechanisms, while somato-dendritic Ca channels contributed to sustain pacemaking and to generate complex bursting at high discharge regimes. Bistability occurred only following Na and Ca channel down-regulation. In addition, specific properties in RNs K currents were required to limit spike transmission frequency along the axon. The model showed how organized electroresponsive functions could emerge from the molecular complexity of PCs and showed that the axon is fundamental to complement ionic channel compartmentalization enabling action potential processing and transmission of specific spike patterns to DCN. PMID:25759640

  17. Compartmentalization of stearoyl-coenzyme A desaturase 1 activity in HepG2 cells*

    PubMed Central

    Yee, Jennifer K.; Mao, Catherine S.; Hummel, Heidi S.; Lim, Shu; Sugano, Sharon; Rehan, Virender K.; Xiao, Gary; Lee, Wai-Nang Paul

    2008-01-01

    Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the conversion of stearate (18:0) to oleate (18:1n-9) and of palmitate (16:0) to palmitoleate (16:1), which are key steps in triglyceride synthesis in the fatty acid metabolic network. This study investigated the role of SCD1 in fatty acid metabolism in HepG2 cells using SCD1 inhibitors and stable isotope tracers. HepG2 cells were cultured with [U-13C]stearate, [U-13C]palmitate, or [1,2-13C]acetate and (1) DMSO, (2) compound CGX0168 or CGX0290, or (3) trans-10,cis-12 conjugated linoleic acid (CLA). 13C incorporation into fatty acids was determined by GC-MS and desaturation indices calculated from the respective ion chromatograms. FAS, SCD1, peroxisome proliferator-activated receptor α, and peroxisome proliferator-activated receptor γ mRNA levels were assessed by semiquantitative RT-PCR. The addition of CGX0168 and CGX0290 decreased the stearate and palmitate desaturation indices in HepG2 cells. CLA led to a decrease in the desaturation of stearate only, but not palmitate. Comparison of desaturation indices based on isotope enrichment ratios differed, depending on the origin of saturated fatty acid. SCD1 gene expression was not affected in any group. In conclusion, the differential effects of SCD1 inhibitors and CLA on SCD1 activity combined with the dependence of desaturation indices on the source of saturated fatty acid strongly support the compartmentalization of desaturation systems. The effects of SCD1 inhibition on fatty acid composition in HepG2 cells occurred through changes in the dynamics of the fatty acid metabolic network and not through transcriptional regulatory mechanisms. PMID:18599738

  18. Compartmentalization of Distinct cAMP Signaling Pathways in Mammalian Sperm*♦

    PubMed Central

    Wertheimer, Eva; Krapf, Dario; de la Vega-Beltran, José L.; Sánchez-Cárdenas, Claudia; Navarrete, Felipe; Haddad, Douglas; Escoffier, Jessica; Salicioni, Ana M.; Levin, Lonny R.; Buck, Jochen; Mager, Jesse; Darszon, Alberto; Visconti, Pablo E.

    2013-01-01

    Fertilization competence is acquired in the female tract in a process known as capacitation. Capacitation is needed for the activation of motility (e.g. hyperactivation) and to prepare the sperm for an exocytotic process known as acrosome reaction. Although the HCO3−-dependent soluble adenylyl cyclase Adcy10 plays a role in motility, less is known about the source of cAMP in the sperm head. Transmembrane adenylyl cyclases (tmACs) are another possible source of cAMP. These enzymes are regulated by stimulatory heterotrimeric Gs proteins; however, the presence of Gs or tmACs in mammalian sperm has been controversial. In this study, we used Western blotting and cholera toxin-dependent ADP-ribosylation to show the Gs presence in the sperm head. Also, we showed that forskolin, a tmAC-specific activator, induces cAMP accumulation in sperm from both WT and Adcy10-null mice. This increase is blocked by the tmAC inhibitor SQ22536 but not by the Adcy10 inhibitor KH7. Although Gs immunoreactivity and tmAC activity are detected in the sperm head, PKA is only found in the tail, where Adcy10 was previously shown to reside. Consistent with an acrosomal localization, Gs reactivity is lost in acrosome-reacted sperm, and forskolin is able to increase intracellular Ca2+ and induce the acrosome reaction. Altogether, these data suggest that cAMP pathways are compartmentalized in sperm, with Gs and tmAC in the head and Adcy10 and PKA in the flagellum. PMID:24129574

  19. Subsurface fluid data from Longyearbyen CO2 storage site: Basin history and compartmentalization

    NASA Astrophysics Data System (ADS)

    Huq, Farhana; Mueller, Kristin; Tore Mørkved, Pål; Johansen, Ingar; Johansen, Harald

    2015-04-01

    The Longyearbyen CO2 storage site, located on the main island of Svalbard at the northwestern margin of the Barents Sea Shelf, is a demonstration project for a "green showcase", which aims to make a full value chain of power generation, CO2 capture and storage by achieving a net zero carbon footprint. The key objective of this study was to assess the local geological conditions for CO2 storage by defining a seal sequence stratigraphy above and within the reservoir from gas and fluid geochemical data. Seven wells were drilled at two sites to collect core material and gas samples at various defined depths. Gas composition (C1-5, CO2) and stable isotope (δ13C) analyses were performed on gas samples obtained from both core material and well heads. In addition, Sr isotope data from residual salts extracted from core material were used to look at compartmentalization. The combined analysis of trends in isotope and gas composition data as a function of depth revealed three major breaks and permitted the identification of three major fluid compartments. These compartments are suggested to be associated with impervious caprock and reservoir barriers. The first break in the data trends occurs at approximately 250-300 m depth, which is interpreted as the depth limit of the meteoric water system. A second hydrologic barrier, most likely produced by reservoir uplift was identified. Finally, a very distinct change in trend around 800 m depth may be associated with an observed significant change in reservoir pressure. Three clear breaks in the geochemical data as a function of depth all point towards an efficient seal sequence and demonstrate the potential for CO2 storage at the Longyearbyen site.

  20. Reservoir compartmentalization caused by mass transport deposition Northwest Stevens pool, Elk Hills Naval Petroleum Reserves, California

    SciTech Connect

    Milliken, M.D.; McJannet, G.S.; Shiflett, D.W.; Deutsch, H.A.

    1996-12-31

    The {open_quotes}A{close_quotes} sands of the Northwest Stevens Pool consist of six major subdivisions (A1-A6) and numerous sublayers. These sands are above the {open_quotes}N Point{close_quotes} stratigraphic marker, making them much younger than most other Stevens sands at Elk Hills. Cores show the A1-A3 sands to be possibly mass transport deposition, primarily debris flows, slumps, and sand injection bodies. The A4-A6 sands are characterized by normally graded sheet-like sand bodies Hospital of traditional outer fan turbidite lithofacies. Most current production from the A1-A2 interval comes from well 373A-7R, are completed waterflood wells that came on line in 1992 at 1400 BOPD. Well 373A-7R is an anomaly in the A1-A2 zone, where average production from the other ten wells is 200 BOPD. Other evidence for compartmentalization in the A1-A2 interval includes sporadic oil-water contacts and drawdown pressures, difficult log correlations, and rapid thickness changes. In 1973, well 362-7R penetrated 220 ft of wet Al sand. The well was redrilled updip and successfully completed in the A1, where the oil-water contact is more than 130 ft lower than the original hole and faulting is not apparent. In 1992, horizontal well 323H-7R unexpectedly encountered an entirely wet Al wedge zone. Reevaluation of the A1-A3 and other sands as mass transport origin is important for modeling initialization and production/development strategies.

  1. Reservoir compartmentalization caused by mass transport deposition Northwest Stevens pool, Elk Hills Naval Petroleum Reserves, California

    SciTech Connect

    Milliken, M.D.; McJannet, G.S. ); Shiflett, D.W. ); Deutsch, H.A. )

    1996-01-01

    The [open quotes]A[close quotes] sands of the Northwest Stevens Pool consist of six major subdivisions (A1-A6) and numerous sublayers. These sands are above the [open quotes]N Point[close quotes] stratigraphic marker, making them much younger than most other Stevens sands at Elk Hills. Cores show the A1-A3 sands to be possibly mass transport deposition, primarily debris flows, slumps, and sand injection bodies. The A4-A6 sands are characterized by normally graded sheet-like sand bodies Hospital of traditional outer fan turbidite lithofacies. Most current production from the A1-A2 interval comes from well 373A-7R, are completed waterflood wells that came on line in 1992 at 1400 BOPD. Well 373A-7R is an anomaly in the A1-A2 zone, where average production from the other ten wells is 200 BOPD. Other evidence for compartmentalization in the A1-A2 interval includes sporadic oil-water contacts and drawdown pressures, difficult log correlations, and rapid thickness changes. In 1973, well 362-7R penetrated 220 ft of wet Al sand. The well was redrilled updip and successfully completed in the A1, where the oil-water contact is more than 130 ft lower than the original hole and faulting is not apparent. In 1992, horizontal well 323H-7R unexpectedly encountered an entirely wet Al wedge zone. Reevaluation of the A1-A3 and other sands as mass transport origin is important for modeling initialization and production/development strategies.

  2. Synapse-specific compartmentalization of signaling cascades for LTP induction in CA3 interneurons

    PubMed Central

    Galván, Emilio J; Pérez-Rosello, Tamara; Gómez-Lira, Gisela; Lara, Erika; Gutiérrez, Rafael; Barrionuevo, Germán

    2015-01-01

    Inhibitory interneurons with somata in strata radiatum and lacunosun-moleculare (SR/L-M) of hippocampal area CA3 receive excitatory input from pyramidal cells via the recurrent collaterals (RC), and the dentate gyrus granule cells via the mossy fibers (MFs). Here we demonstrate that Hebbian long-term potentiation (LTP) at RC synapses on SR/L-M interneurons requires the concomitant activation of calcium-impermeable AMPARs (CI- AMPARs) and NMDARs. RC LTP was prevented by voltage clamping the postsynaptic cell during high-frequency stimulation (HFS; 3 trains of 100 pulses delivered at 100 Hz every 10 s), with intracellular injections of the Ca2+ chelator BAPTA (20 mM), and with the N-methyl-D-aspartate receptor (NMDAR) antagonist D-AP5. In separate experiments, RC and MF inputs converging onto the same interneuron were sequentially activated. We found that RC LTP induction was blocked by inhibitors of the calcium/calmodulin-dependent protein kinase II (CaMKII; KN-62, 10 μM or KN-93, 10 μM) but MF LTP was CaMKII independent. Conversely, the application of the protein kinase A (PKA) activators forskolin/IBMX(50 μM/25 μM) potentiated MF EPSPs but not RC EPSPs. Together these data indicate that the aspiny dendrites of SR/L-M interneurons compartmentalize synaptic-specific Ca2+ signaling required for LTP induction at RC and MF synapses. We also show that the two signal transduction cascades converge to activate a common effector, protein kinase C (PKC). Specifically, LTP at RC and MF synapses on the same SR/LM interneuron was blocked by postsynaptic injections of chelerythrine (10 μM). These data indicate that both forms of LTP share a common mechanism involving PKC-dependent signaling modulation. PMID:25637803

  3. Structural compartmentalization in a decapitated anticline: The example of the Divide Creek fractured reservoir, Piceance Basin

    SciTech Connect

    Hoak, T.E.; Klawitter, A.L. )

    1996-01-01

    Integrated analysis of high-resolution aeromagnetic and remote sensing data, confirmed by field geology, seismic and production data, demonstrates reservoir compartmentalization within the Divide Creek Field, southeast Piceance Basin. Topographic constraints and Federal land use restrictions, limit the ability to collect extensive seismic data across this complex structure and precludes complete characterization of subsurface structure by direct methods. Integrated analysis of airborne aeromagnetic data with TM (thematic mapper) and SAR (synthetic aperture radar) data, permit the resolution of the 3D complexity of this fold and its associated reservoir not easily defined using conventional 2D seismic. The Divide Creek Anticline is a decapitated pop-up anticline. The pop-up anticline that originally formed along a deeper, Eagle Valley Evaporite detachment surface has been [open quotes]decapitated[close quotes] along a shallower Manoos-level detachment that translates the shallows pop-up anticlinal axis to the west. The fold is further segmented by normal faults trending axis-perpendicular to its axis that create distinct reservoir compartments. Processing of aeromagnetic data using multiple bandpass filters demonstrates three detachments in the fold, and the 3D geometry of the detachments. Understanding timing of these structures is critical for constraining fracture genesis and gas migration models, Oriented fracture data from surficial studies, aeromagnetic data, remote sensing imagery, and subsurface core delineated three primary trends. These trends correspond to axis-parallel, axis-perpendicular and an older oblique regional fracture sets. This fracture permeability has made Divide Creek Field the most prolific Piceance Basin tight gas sand field.

  4. Structural compartmentalization in a decapitated anticline: The example of the Divide Creek fractured reservoir, Piceance Basin

    SciTech Connect

    Hoak, T.E.; Klawitter, A.L.

    1996-12-31

    Integrated analysis of high-resolution aeromagnetic and remote sensing data, confirmed by field geology, seismic and production data, demonstrates reservoir compartmentalization within the Divide Creek Field, southeast Piceance Basin. Topographic constraints and Federal land use restrictions, limit the ability to collect extensive seismic data across this complex structure and precludes complete characterization of subsurface structure by direct methods. Integrated analysis of airborne aeromagnetic data with TM (thematic mapper) and SAR (synthetic aperture radar) data, permit the resolution of the 3D complexity of this fold and its associated reservoir not easily defined using conventional 2D seismic. The Divide Creek Anticline is a decapitated pop-up anticline. The pop-up anticline that originally formed along a deeper, Eagle Valley Evaporite detachment surface has been {open_quotes}decapitated{close_quotes} along a shallower Manoos-level detachment that translates the shallows pop-up anticlinal axis to the west. The fold is further segmented by normal faults trending axis-perpendicular to its axis that create distinct reservoir compartments. Processing of aeromagnetic data using multiple bandpass filters demonstrates three detachments in the fold, and the 3D geometry of the detachments. Understanding timing of these structures is critical for constraining fracture genesis and gas migration models, Oriented fracture data from surficial studies, aeromagnetic data, remote sensing imagery, and subsurface core delineated three primary trends. These trends correspond to axis-parallel, axis-perpendicular and an older oblique regional fracture sets. This fracture permeability has made Divide Creek Field the most prolific Piceance Basin tight gas sand field.

  5. Multiple Facets of cAMP Signalling and Physiological Impact: cAMP Compartmentalization in the Lung

    PubMed Central

    Oldenburger, Anouk; Maarsingh, Harm; Schmidt, Martina

    2012-01-01

    Therapies involving elevation of the endogenous suppressor cyclic AMP (cAMP) are currently used in the treatment of several chronic inflammatory disorders, including chronic obstructive pulmonary disease (COPD). Characteristics of COPD are airway obstruction, airway inflammation and airway remodelling, processes encompassed by increased airway smooth muscle mass, epithelial changes, goblet cell and submucosal gland hyperplasia. In addition to inflammatory cells, airway smooth muscle cells and (myo)fibroblasts, epithelial cells underpin a variety of key responses in the airways such as inflammatory cytokine release, airway remodelling, mucus hypersecretion and airway barrier function. Cigarette smoke, being next to environmental pollution the main cause of COPD, is believed to cause epithelial hyperpermeability by disrupting the barrier function. Here we will focus on the most recent progress on compartmentalized signalling by cAMP. In addition to G protein-coupled receptors, adenylyl cyclases, cAMP-specific phospho-diesterases (PDEs) maintain compartmentalized cAMP signalling. Intriguingly, spatially discrete cAMP-sensing signalling complexes seem also to involve distinct members of the A-kinase anchoring (AKAP) superfamily and IQ motif containing GTPase activating protein (IQGAPs). In this review, we will highlight the interaction between cAMP and the epithelial barrier to retain proper lung function and to alleviate COPD symptoms and focus on the possible molecular mechanisms involved in this process. Future studies should include the development of cAMP-sensing multiprotein complex specific disruptors and/or stabilizers to orchestrate cellular functions. Compartmentalized cAMP signalling regulates important cellular processes in the lung and may serve as a therapeutic target. PMID:24281338

  6. A multi-compartment cell repopulation model allowing for inter-compartmental migration following radiation exposure, applied to leukaemia.

    PubMed

    Little, Mark P

    2007-03-01

    There is much uncertainty about cancer risks at the high radiation doses used in radiotherapy (RT). It has generally been assumed that cancer induction decreases rapidly at high doses due to cell killing. However, this is not seen in all RT groups, and a model recently developed by Sachs and Brenner [2005. Solid tumor risks after high doses of ionizing radiation. Proc. Natl Acad. Sci. USA 102, 13040-13045] proposed a mechanism for repopulation of cells after radiation exposure that explained why this might happen, at least for solid tumours. In this paper, this model is generalized to allow for heterogeneity in the dose received, and various alternate patterns of repopulation are also considered. The model is fitted to the Japanese atomic bomb survivor leukaemia incidence data, and data for various therapeutically irradiated groups. Two sets of parameters from these model fits are used to assess the sensitivity of model predictions. It is shown that in general allowing for heterogeneity in dose distribution and haematopoietic stem cell migration results in lower risks than the same average dose administered uniformly and without such migration, although this does not hold in the limiting case of complete stem cell repopulation between radiation dose fractions. We also investigate the difference made by assuming a compartmental repopulation signal, and a global repopulation signal. In general we show that in the absence of stochastic extinction, compartmental repopulation always predicts a larger number of mutated cells than global repopulation. However, in certain dose regimes stochastic extinction cannot be ignored, and in these cases the numbers of mutated cells predicted with global repopulation can exceed that for compartmental repopulation. In general, mutant cell numbers are highly overdispersed, with variance much greater than the mean.

  7. Sequence stratigraphic and synsedimentary tectonic controls on reservoir compartmentalization in a transgressive sequence set: Almond formation, southwest Wyoming

    SciTech Connect

    Krystinik, L.F.; Mead, R.H. )

    1996-01-01

    The Campanian upper Almond Formation in Southwestern Wyoming contains at least 15 aggradational to backstepping microtidal to low mesotidal barrier/shoreline complexes laid down during a period of net transgression from 72 to 70.5 million years ago. Reservoir compartmentalization in the upper Almond occurs at several scales, including an aggradational to retrogradations sequence set composed of 3 retrogradational parasequence sets; numerous parasequences, and diverse barrier sub-facies units. The lowstand shorelines of these sequence sets stack aggradationally prior to transgression by a really extensive, marine mudstone horizons which separate the sequences. Highstand systems tracts are poorly preserved, often completely removed below fourth of fifth order sequence boundaries which cause seaward jumps of facies in excess of 30 Km and place fluvial sediment, coal and lagoonal deposits abruptly over marine mudstone. Each sequence in the upper Almond is composed of several parasequences (sanding-upward, storm-dominated barrier shorefaces) which intercalate with marine mudstone to the east and grade into oyster-bearing, organic-rich lagoonal mudstone to the west. Compartmentalization in the barrier complexes occurs at most parasequence boundaries and in association with major sub-facies; boundaries (barrier margins, tidal inlets, flood-tidal deltas, washover fans). Further reservoir compartmentalization is induced by synsedimentary faulting and subsidence which locally preserve isolated reservoir-quality barrier/shoreline sandstone bodies by dropping them below the depth of ravinement (5-30 m). The recognition of synsedimentary faulting and subsequent ravinement is critical to accurate sequence stratigraphic analysis and for prediction of reservoir compartments.

  8. Sequence stratigraphic and synsedimentary tectonic controls on reservoir compartmentalization in a transgressive sequence set: Almond formation, southwest Wyoming

    SciTech Connect

    Krystinik, L.F.; Mead, R.H.

    1996-12-31

    The Campanian upper Almond Formation in Southwestern Wyoming contains at least 15 aggradational to backstepping microtidal to low mesotidal barrier/shoreline complexes laid down during a period of net transgression from 72 to 70.5 million years ago. Reservoir compartmentalization in the upper Almond occurs at several scales, including an aggradational to retrogradations sequence set composed of 3 retrogradational parasequence sets; numerous parasequences, and diverse barrier sub-facies units. The lowstand shorelines of these sequence sets stack aggradationally prior to transgression by a really extensive, marine mudstone horizons which separate the sequences. Highstand systems tracts are poorly preserved, often completely removed below fourth of fifth order sequence boundaries which cause seaward jumps of facies in excess of 30 Km and place fluvial sediment, coal and lagoonal deposits abruptly over marine mudstone. Each sequence in the upper Almond is composed of several parasequences (sanding-upward, storm-dominated barrier shorefaces) which intercalate with marine mudstone to the east and grade into oyster-bearing, organic-rich lagoonal mudstone to the west. Compartmentalization in the barrier complexes occurs at most parasequence boundaries and in association with major sub-facies; boundaries (barrier margins, tidal inlets, flood-tidal deltas, washover fans). Further reservoir compartmentalization is induced by synsedimentary faulting and subsidence which locally preserve isolated reservoir-quality barrier/shoreline sandstone bodies by dropping them below the depth of ravinement (5-30 m). The recognition of synsedimentary faulting and subsequent ravinement is critical to accurate sequence stratigraphic analysis and for prediction of reservoir compartments.

  9. Hepatic compartmentalization of exhausted and regulatory cells in HIV/HCV-coinfected patients.

    PubMed

    Barrett, L; Trehanpati, N; Poonia, S; Daigh, L; Sarin, S Kumar; Masur, H; Kottilil, S

    2015-03-01

    Accelerated intrahepatic hepatitis C virus (HCV) pathogenesis is likely the result of dysregulation within both the innate and adaptive immune compartments, but the exact contribution of peripheral blood and liver lymphocyte subsets remains unclear. Prolonged activation and expansion of immunoregulatory cells have been thought to play a role. We determined immune cell subset frequency in contemporaneous liver and peripheral blood samples from chronic HCV-infected and HIV/HCV-coinfected individuals. Peripheral blood mononuclear cells (PBMC) and biopsy-derived liver-infiltrating lymphocytes from 26 HIV/HCV-coinfected, 10 chronic HCV-infected and 10 HIV-infected individuals were assessed for various subsets of T and B lymphocytes, dendritic cell, natural killer (NK) cell and NK T-cell frequency by flow cytometry. CD8(+) T cells expressing the exhaustion marker PD-1 were increased in HCV-infected individuals compared with uninfected individuals (P = 0.02), and HIV coinfection enhanced this effect (P = 0.005). In the liver, regulatory CD4(+) CD25(+) Foxp3(+) T cells, as well as CD4(+) CD25(+) PD1(+) T cells, were more frequent in HIV/HCV-coinfected than in HCV-monoinfected samples (P < 0.001). HCV was associated with increased regulatory T cells, PD-1(+) T cells and decreased memory B cells, regardless of HIV infection (P ≤ 0.005 for all). Low CD8(+) expression was observed only in PD-1(+) CD8(+) T cells from HCV-infected individuals and healthy controls (P = 0.002) and was associated with enhanced expansion of exhausted CD8(+) T cells when exposed in vitro to PHA or CMV peptides. In conclusion, in HIV/HCV coinfection, ongoing HCV replication is associated with increased regulatory and exhausted T cells in the periphery and liver that may impact control of HCV. Simultaneous characterization of liver and peripheral blood highlights the disproportionate intrahepatic compartmentalization of immunoregulatory T cells, which may contribute to establishment of chronicity and

  10. Structural localization and origin of compartmentalized fluid flow, Comstock lode, Virginia City, Nevada

    USGS Publications Warehouse

    Berger, B.R.; Tingley, J.V.; Drew, L.J.

    2003-01-01

    Bonanza-grade orebodies in epithermal-style mineral deposits characteristically occur as discrete zones within spatially more extensive fault and/or fracture systems. Empirically, the segregation of such systems into compartments of higher and lower permeability appears to be a key process necessary for high-grade ore formation and, most commonly, it is such concentrations of metals that make an epithermal vein district world class. In the world-class silver- and gold-producing Comstock mining district, Nevada, several lines of evidence lead to the conclusion that the Comstock lode is localized in an extensional stepover between right-lateral fault zones. This evidence includes fault geometries, kinematic indicators of slip, the hydraulic connectivity of faults as demonstrated by veins and dikes along faults, and the opening of a normal-fault-bounded, asymmetric basin between two parallel and overlapping northwest-striking, lateral- to lateral-oblique-slip fault zones. During basin opening, thick, generally subeconomic, banded quartz-adularia veins were deposited in the normal fault zone, the Comstock fault, and along one of the bounding lateral fault zones, the Silver City fault. As deformation continued, the intrusion of dikes and small plugs into the hanging wall of the Comstock fault zone may have impeded the ability of the stepover to accommodate displacement on the bounding strike-slip faults through extension within the stepover. A transient period of transpressional deformation of the Comstock fault zone ensued, and the early-stage veins were deformed through boudinaging and hydraulic fragmentation, fault-motion inversion, and high- and low-angle axial rotations of segments of the fault planes and some fault-bounded wedges. This deformation led to the formation of spatially restricted compartments of high vertical permeability and hydraulic connectivity and low lateral hydraulic connectivity. Bonanza orebodies were formed in the compartmentalized zones of

  11. Does location of patellofemoral chondral lesion influence outcome after Oxford medial compartmental knee arthroplasty?

    PubMed Central

    Konan, S.; Haddad, F. S.

    2016-01-01

    Aims Medial unicompartmental knee arthroplasty (UKA) is associated with successful outcomes in carefully selected patient cohorts. We hypothesised that severity and location of patellofemoral cartilage lesions significantly influences functional outcome after Oxford medial compartmental knee arthroplasty. Patients and Methods We reviewed 100 consecutive UKAs at minimum eight-year follow-up (96 to 132). A single surgeon performed all procedures. Patients were selected based on clinical and plain radiographic assessment. All patients had end-stage medial compartment osteoarthritis (OA) with sparing of the lateral compartment and intact anterior cruciate ligaments. None of the patients had end-stage patellofemoral OA, but patients with anterior knee pain or partial thickness chondral loss were not excluded. There were 57 male and 43 female patients. The mean age at surgery was 69 years (41 to 82). At surgery the joint was carefully inspected for patellofemoral chondral loss and this was documented based on severity of cartilage loss (0 to 4 Outerbridge grading) and topographic location (medial, lateral, central, and superior or inferior). Functional scores collected included Oxford Knee Score (OKS), patient satisfaction scale and University College Hospital (UCH) knee score. Intraclass correlation was used to compare chondral damage to outcomes. Results All patients documented significant improvement in pain and improved functional scores at mid-term follow-up. There were four revisions (mean 2.9 years, 2 to 4; standard deviation (sd) 0.9) in this cohort, three for tibial loosening and one for femoral loosening. There was one infection that was treated with debridement and insert exchange. The mean OKS improved from 23.2 (sd 7.1) to 39.1 (sd 6.9); p < 0.001. The cohort with central and lateral grade 3 patellofemoral OA documented lower mean satisfaction with pain (90, sd 11.8) and function (87.5, sd 10.3) on the patient satisfaction scale. On the UCH scale, patients

  12. Measurement of intra-abdominal pressure in large incisional hernia repair to prevent abdominal compartmental syndrome

    PubMed Central

    ANGELICI, A.M.; PEROTTI, B.; DEZZI, C.; AMATUCCI, C.; MANCUSO, G.; CARONNA, R.; PALUMBO, P.

    2016-01-01

    Introduction The repair of large incisional hernias may occasionally lead to a substantial increase in intra-abdominal pressure (IAP), and rarely to abdominal compartmental syndrome (ACS) with subsequent respiratory, vascular, and visceral complications. Measurement of the IAP has recently become a common practice in monitoring critical patients, even though such measurements were obtained in the early 1900s. Patients and Methods A prospective study involving 54 patients undergoing elective abdominal wall gap repair (mean length, 17.4 cm) with a tension-free technique after incisional hernia was conducted. The purpose of the study was to determine whether or not urinary pressure for indirect IAP measurement is a reliable method for the early identification of patients with a higher risk of developing ACS. IAP measurements were performed using a Foley catheter connected to a HOLTECH® medical manometer. IAP values were determined pre-operatively, after anesthetic induction, upon patient awakening, upon patient arrival in the ward after surgery, and 24 h after surgery before removing the catheter. All patients were treated by the same surgical team using a prosthetic composite mesh (PARIETEX®). Results Incisional hernia repair caused an increase in the mean IAP score of 2.68 mmHg in 47 of 54 patients (87.04%); the IAP was decreased in two patients (3.7%) and remained equal in five patients before and 24 h after surgery (9.26%). FEV-1, measured 24 h after surgery, increased in 50 patients (92.6%), remained stable in two patients (3.7%), and decreased in two patients (3.7%). The mean increase in FEV-1 was 0.0676 L (maximum increase = 0.42 L and minimum increase = 0.01 L) in any patient who developed ACS. Conclusions Measurement of urinary bladder pressure has been shown to be easy to perform and free of complications. Measurement of urinary bladder pressure can also be a useful tool to identify patients with a higher risk of developing ACS. PMID:27142823

  13. The Subcellular Compartmentalization of Arginine Metabolizing Enzymes and Their Role in Endothelial Dysfunction

    PubMed Central

    Chen, Feng; Lucas, Rudolf; Fulton, David

    2013-01-01

    The endothelial production of nitric oxide (NO) mediates endothelium-dependent vasorelaxation and restrains vascular inflammation, smooth muscle cell proliferation, and platelet aggregation. Impaired production of NO is a hallmark of endothelial dysfunction and promotes the development of cardiovascular disease. In endothelial cells, NO is generated by endothelial nitric oxide synthase (eNOS) through the conversion of its substrate, l-arginine to l-citrulline. Reduced access to l-arginine has been proposed as a major mechanism underlying reduced eNOS activity and NO production in cardiovascular disease. The arginases (Arg1 and Arg2) metabolize l-arginine to generate l-ornithine and urea and increased expression of arginase has been proposed as a mechanism of reduced eNOS activity secondary to the depletion of l-arginine. Indeed, supplemental l-arginine and suppression of arginase activity has been shown to improve endothelium-dependent relaxation and ameliorate cardiovascular disease. However, this simple relationship is complicated by observations that l-arginine concentrations in endothelial cells remain sufficiently high to support NO synthesis. Accordingly, the subcellular compartmentalization of intracellular l-arginine into poorly interchangeable pools has been proposed to allow for the local depletion of pools or pockets of l-arginine. In agreement with this, there is considerable evidence supporting the importance of the subcellular localization of l-arginine metabolizing enzymes. In endothelial cells in vitro and in vivo, eNOS is found in discrete intracellular locations and the capacity to generate NO is heavily influenced by its localization inside the cell. Arg1 and Arg2 also reside in different subcellular environments and are thought to differentially influence endothelial function. The plasma membrane solute transporter, CAT-1 and the arginine recycling enzyme, arginosuccinate lyase, co-localize with eNOS and facilitate NO release. Herein, we

  14. Multi-hollow polymer microspheres with enclosed surfaces and compartmentalized voids prepared by seeded swelling polymerization method.

    PubMed

    Tian, Qiong; Yu, Demei; Zhu, Kaiming; Hu, Guohe; Zhang, Lifeng; Liu, Yuhang

    2016-07-01

    Multi-hollow particles have drawn extensive research interest due to their high specific areas and abundant inner voids, whereas their convenient synthesis still remains challenging. In this paper, we report a simple and convenient method based on seeded swelling polymerization to prepare the multi-hollow microspheres with enclosed surfaces and compartmentalized voids using monodisperse poly (styrene-co-sodium 4-vinylbenzenesulfonate) microspheres as seed particles. A formation mechanism of the multi-hollow structure was proposed involving the processes of water absorption, coalescence and stabilization of water domains, immobilization of multi-hollow structure, and coverage of surface dimples. The influencing parameters on the morphology of the microspheres, including weight ratio of sodium 4-vinylbenzenesulfonate to styrene in the seed particles, dosage of the swelling monomer and the crosslinking agent were systematically investigated. The internal structure of the resultant microspheres could be tuned from solid to multi-hollow by controlling over these parameters. Multi-hollow microspheres with compartmentalized chambers, smooth surfaces and narrow size distributions were obtained as a result.

  15. TspanC8 tetraspanins differentially regulate the cleavage of ADAM10 substrates, Notch activation and ADAM10 membrane compartmentalization.

    PubMed

    Jouannet, Stéphanie; Saint-Pol, Julien; Fernandez, Laurent; Nguyen, Viet; Charrin, Stéphanie; Boucheix, Claude; Brou, Christel; Milhiet, Pierre-Emmanuel; Rubinstein, Eric

    2016-05-01

    The metalloprotease ADAM10 mediates the shedding of the ectodomain of various cell membrane proteins, including APP, the precursor of the amyloid peptide Aβ, and Notch receptors following ligand binding. ADAM10 associates with the members of an evolutionary conserved subgroup of tetraspanins, referred to as TspanC8, which regulate its exit from the endoplasmic reticulum. Here we show that 4 of these TspanC8 (Tspan5, Tspan14, Tspan15 and Tspan33) which positively regulate ADAM10 surface expression levels differentially impact ADAM10-dependent Notch activation and the cleavage of several ADAM10 substrates, including APP, N-cadherin and CD44. Sucrose gradient fractionation, single molecule tracking and quantitative mass-spectrometry analysis of the repertoire of molecules co-immunoprecipitated with Tspan5, Tspan15 and ADAM10 show that these two tetraspanins differentially regulate ADAM10 membrane compartmentalization. These data represent a unique example where several tetraspanins differentially regulate the function of a common partner protein through a distinct membrane compartmentalization. PMID:26686862

  16. Multi-hollow polymer microspheres with enclosed surfaces and compartmentalized voids prepared by seeded swelling polymerization method.

    PubMed

    Tian, Qiong; Yu, Demei; Zhu, Kaiming; Hu, Guohe; Zhang, Lifeng; Liu, Yuhang

    2016-07-01

    Multi-hollow particles have drawn extensive research interest due to their high specific areas and abundant inner voids, whereas their convenient synthesis still remains challenging. In this paper, we report a simple and convenient method based on seeded swelling polymerization to prepare the multi-hollow microspheres with enclosed surfaces and compartmentalized voids using monodisperse poly (styrene-co-sodium 4-vinylbenzenesulfonate) microspheres as seed particles. A formation mechanism of the multi-hollow structure was proposed involving the processes of water absorption, coalescence and stabilization of water domains, immobilization of multi-hollow structure, and coverage of surface dimples. The influencing parameters on the morphology of the microspheres, including weight ratio of sodium 4-vinylbenzenesulfonate to styrene in the seed particles, dosage of the swelling monomer and the crosslinking agent were systematically investigated. The internal structure of the resultant microspheres could be tuned from solid to multi-hollow by controlling over these parameters. Multi-hollow microspheres with compartmentalized chambers, smooth surfaces and narrow size distributions were obtained as a result. PMID:27046772

  17. 3-D seismic evidence of the effects of carbonate karst collapse on overlying clastic stratigraphy and reservoir compartmentalization

    SciTech Connect

    Hardage, B.A.; Carr, D.L.; Simmons, J.L. Jr.; Jons, R.A.; Lancaster, D.E.; Elphick, R.Y.; Pendleton, V.M.

    1996-09-01

    A multidisciplinary team, composed of stratigraphers, petrophysicists, reservoir engineers, and geophysicists, studied a portion of Boonsville gas field in the Fort Worth Basin of north-central Texas to determine how modern techniques can be combined to understand the mechanisms by which fluvio-deltaic depositional processes create reservoir compartmentalization in a low- to moderate-accommodation basin. An extensive database involving well logs, cores, production, and pressure data from more than 200 wells, 26 mi{sup 2} of 3-D seismic data, vertical seismic profiles, and checkshots was assembled to support this investigation. The authors found the most important geologic influence on stratigraphy and reservoir compartmentalization in this basin to be the existence of numerous karst collapse chimneys over the area covered. These near-vertical karst collapses originated in, or near, the deep Ordovician-age Ellenburger carbonate section and created vertical chimneys extending as high as 2,500 ft above their point of origin, causing significant disruptions in the overlying clastic strata.

  18. Buds from the tree of life: linking compartmentalized prokaryotes and eukaryotes by a non-hyperthermophile common ancestor and implications for understanding Archaean microbial communities

    NASA Astrophysics Data System (ADS)

    Fuerst, John A.; Nisbet, Euan G.

    2004-07-01

    The origin of the first nucleated eukaryote and the nature of the last common ancestor of the three domains of life are major questions in the evolutionary biology of cellular life on Earth, the solutions to which may be linked. Planctomycetes are unusual compartmentalized bacteria that include a membrane-bounded nucleoid. The possibility that they constitute a very deep branch of the domain Bacteria suggests a model for the evolution of the three domains of life from a last common ancestor that was a mesophile or moderate thermophile with a compartmentalized eukaryote-like cell plan. Planctomycetes and some members of the domain Archaea may have retained cell compartmentalization present in an original eukaryote-like last common ancestor of the three domains of life. The implications of this model for possible habitats of the early evolution of domains of cellular life and for interpretation of geological evidence relating to those habitats and the early emergence of life are examined here.

  19. Commissioning. Law of the jungle.

    PubMed

    Moore, Alison

    2006-12-14

    Many managers worry that payment by results and the separation of commissioners and providers encourages competition and undermines collaboration. But the NHS will always need organisations to work together for the benefit of patients. Managers must learn to compete and collaborate simultaneously--and live with uncertainty about their careers, as not will will find posts in the new era. PMID:17252857

  20. The urban jungle and allergy.

    PubMed

    Thompson, James L; Thompson, Jonathan E

    2003-08-01

    The urban forest is the assemblage of trees, shrubs, and other plants that occupy the urban and suburban zone. In urban areas, the number of potentially allergenic plants has grown rapidly as the diversity of plants increases. The recommended street trees of many cities are allergenic species that are well known to allergy clinicians. Some of the most commonly planted trees in urban zones are known to be the greatest producers of pollen. These trees are situated in close proximity to humans, either at home, at work, or on their travel routes between locations. There are common misconceptions about the plants that do and do not cause allergy. It generally has been considered that insect-pollinated plants with showy flowers are allergy safe; however, when these species are planted in close proximity to people, as they are in urban landscaping, the pollen that leaks from the flowers is often enough to cause an allergic reaction. With increasing emphasis on green space in urban areas, it is advisable to evaluate what is being planted, how much is planted, and the plants' potential for triggering allergy.

  1. Communication Between the Cell Membrane and the Nucleus: Role of Protein Compartmentalization

    SciTech Connect

    Lelievre, Sophie A; Bissell, Mina J

    1998-10-21

    Understanding how the information is conveyed from outside to inside the cell is a critical challenge for all biologists involved in signal transduction. The flow of information initiated by cell-cell and cell-extracellular matrix contacts is mediated by the formation of adhesion complexes involving multiple proteins. Inside adhesion complexes, connective membrane skeleton (CMS) proteins are signal transducers that bind to adhesion molecules, organize the cytoskeleton, and initiate biochemical cascades. Adhesion complex-mediated signal transduction ultimately directs the formation of supramolecular structures in the cell nucleus, as illustrated by the establishment of multi complexes of DNA-bound transcription factors, and the redistribution of nuclear structural proteins to form nuclear subdomains. Recently, several CMS proteins have been observed to travel to the cell nucleus, suggesting a distinctive role for these proteins in signal transduction. This review focuses on the nuclear translocation of structural signal transducers of the membrane skeleton and also extends our analysis to possible translocation of resident nuclear proteins to the membrane skeleton. This leads us to envision the communication between spatially distant cellular compartments (i.e., membrane skeleton and cell nucleus) as a bidirectional flow of information (a dynamic reciprocity) based on subtle multilevel structural and biochemical equilibria. At one level, it is mediated by the interaction between structural signal transducers and their binding partners, at another level it may be mediated by the balance and integration of signal transducers in different cellular compartments.

  2. Compartmental modeling of rat macular primary afferents from three-dimensional reconstructions of transmission electron micrographs of serial sections.

    PubMed

    Chimento, T C; Doshay, D G; Ross, M D

    1994-05-01

    1. We cut serial sections through the medial part of the rat vestibular macula for transmission electron microscopic (TEM) examination, computer-assisted three-dimensional (3-D) reconstruction, and compartmental modeling. The ultrastructural research showed that many primary vestibular neurons have an unmyelinated segment, often branched, that extends between the heminode [putative site of the spike initiation zone (SIZ)] and the expanded terminal(s) (calyx, calyces). These segments, termed the neuron branches, and the calyces frequently have spinelike processes of various dimensions that morphologically are afferent, efferent, or reciprocal to other macular neural elements. The purpose of this research was to determine whether morphometric data obtained ultrastructurally were essential to compartmental models [i.e., they influenced action potential (AP) generation, latency, or amplitude] or whether afferent parts could be collapsed into more simple units without markedly affecting results. We used the compartmental modeling program NEURON for this research. 2. In the first set of simulations we studied the relative importance of small variations in process morphology on distant depolarization. A process was placed midway along an isolated piece of a passive neuron branch. The dimensions of the four processes corresponded to actual processes in the serial sections. A synapse, placed on the head of each process, was activated and depolarization was recorded at the end of the neuron branch. When we used 5 nS synaptic conductance, depolarization varied by 3 mV. In a systematic study over a representative range of stem dimensions, depolarization varied by 15.7 mV. Smaller conductances produced smaller effects. Increasing membrane resistivity from 5,000 to 50,000 omega cm2 had no significant effect. 3. In a second series of simulations, using whole primary afferents, we examined the combined effects of process location and afferent morphology on depolarization magnitude

  3. Complex-shaped three-dimensional multi-compartmental microparticles generated by diffusional and Marangoni microflows in centrifugally discharged droplets

    PubMed Central

    Hayakawa, Masayuki; Onoe, Hiroaki; Nagai, Ken H.; Takinoue, Masahiro

    2016-01-01

    We report a versatile method for the generation of complex-shaped three-dimensional multi-compartmental (3D-MC) microparticles. Complex-shaped microparticles have recently received much attention for potential application in self-assemblies, micromachines, and biomedical and environmental engineering. Here, we have developed a method based on 3D nonequilibrium-induced microflows (Marangoni and diffusional flows) of microdroplets that are discharged from the tip of a thin capillary in a simple centrifugal microfluidic device. The microparticle shapes can be tuned by the partial dissolution of specific compartments and by the deformation of the precursor microdroplets by manipulating the 3D microflows. We believe that this method will have wide applications in nano- and microscience and technologies. PMID:26861767

  4. Effect of compartmentalization of donor and acceptor on the ultrafast resonance energy transfer from DAPI to silver nanoclusters

    NASA Astrophysics Data System (ADS)

    Prajapati, Roopali; Chatterjee, Surajit; Kannaujiya, Krishna K.; Mukherjee, Tushar Kanti

    2016-06-01

    The mechanism and dynamics of excitation energy transfer (EET) from photo-excited 4',6-diamidino-2-phenylindole (DAPI) to silver nanoclusters (Ag NCs) and its subsequent modulation in the presence of cationic polymer poly(diallyldimethylammonium chloride) (PDADMAC) and Calf Thymus DNA (CT-DNA) have been demonstrated using steady-state fluorescence and femtosecond fluorescence upconversion techniques. The synthesized Ag NCs were characterized using FTIR, mass spectrometry, XPS, HRTEM, DLS, UV-Vis and PL spectroscopy. Mass spectrometric analysis reveals the formation of ultrasmall Ag4 NCs with a small amount of Ag5 NCs. UV-Vis and PL spectra reveal distinct molecular-like optoelectronic behaviour of these ultrasmall Ag NCs. The dihydrolipoic acid-capped Ag NCs strongly quench the fluorescence of DAPI with concomitant increase in its photoluminescence (PL) intensity at 675 nm. This steady-state fluorescence quenching proceeds with a significant shortening of the fluorescence lifetime of DAPI in the presence of Ag NCs, signifying the nonradiative Förster resonance energy transfer (FRET) from DAPI to Ag NCs. Various energy transfer parameters have been estimated from FRET theory. The present FRET pair shows a characteristic Förster distance of 2.45 nm and can be utilized as a reporter of short-range distances in various FRET based applications. Moreover, this nonradiative FRET is completely suppressed in the presence of both 0.2 wt% PDADMAC and CT-DNA. Our results reveal selective compartmentalization of Ag NCs and DAPI in the presence of 0.2 wt% PDADMAC and CT-DNA, respectively. This selective compartmentalization of donor and acceptor and the subsequent modification of the FRET process may find application in various sensing, photovoltaic, and light harvesting applications.The mechanism and dynamics of excitation energy transfer (EET) from photo-excited 4',6-diamidino-2-phenylindole (DAPI) to silver nanoclusters (Ag NCs) and its subsequent modulation in the presence

  5. The cellular and compartmental profile of mouse retinal glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, and ~P transferring kinases

    PubMed Central

    Rueda, Elda M.; Johnson, Jerry E.; Giddabasappa, Anand; Swaroop, Anand; Brooks, Matthew J.; Sigel, Irena; Chaney, Shawnta Y.

    2016-01-01

    Purpose The homeostatic regulation of cellular ATP is achieved by the coordinated activity of ATP utilization, synthesis, and buffering. Glucose is the major substrate for ATP synthesis through glycolysis and oxidative phosphorylation (OXPHOS), whereas intermediary metabolism through the tricarboxylic acid (TCA) cycle utilizes non-glucose-derived monocarboxylates, amino acids, and alpha ketoacids to support mitochondrial ATP and GTP synthesis. Cellular ATP is buffered by specialized equilibrium-driven high-energy phosphate (~P) transferring kinases. Our goals were twofold: 1) to characterize the gene expression, protein expression, and activity of key synthesizing and regulating enzymes of energy metabolism in the whole mouse retina, retinal compartments, and/or cells and 2) to provide an integrative analysis of the results related to function. Methods mRNA expression data of energy-related genes were extracted from our whole retinal Affymetrix microarray data. Fixed-frozen retinas from adult C57BL/6N mice were used for immunohistochemistry, laser scanning confocal microscopy, and enzymatic histochemistry. The immunoreactivity levels of well-characterized antibodies, for all major retinal cells and their compartments, were obtained using our established semiquantitative confocal and imaging techniques. Quantitative cytochrome oxidase (COX) and lactate dehydrogenase (LDH) activity was determined histochemically. Results The Affymetrix data revealed varied gene expression patterns of the ATP synthesizing and regulating enzymes found in the muscle, liver, and brain. Confocal studies showed differential cellular and compartmental distribution of isozymes involved in glucose, glutamate, glutamine, lactate, and creatine metabolism. The pattern and intensity of the antibodies and of the COX and LDH activity showed the high capacity of photoreceptors for aerobic glycolysis and OXPHOS. Competition assays with pyruvate revealed that LDH-5 was localized in the photoreceptor

  6. Complex-shaped three-dimensional multi-compartmental microparticles generated by diffusional and Marangoni microflows in centrifugally discharged droplets

    NASA Astrophysics Data System (ADS)

    Hayakawa, Masayuki; Onoe, Hiroaki; Nagai, Ken H.; Takinoue, Masahiro

    2016-02-01

    We report a versatile method for the generation of complex-shaped three-dimensional multi-compartmental (3D-MC) microparticles. Complex-shaped microparticles have recently received much attention for potential application in self-assemblies, micromachines, and biomedical and environmental engineering. Here, we have developed a method based on 3D nonequilibrium-induced microflows (Marangoni and diffusional flows) of microdroplets that are discharged from the tip of a thin capillary in a simple centrifugal microfluidic device. The microparticle shapes can be tuned by the partial dissolution of specific compartments and by the deformation of the precursor microdroplets by manipulating the 3D microflows. We believe that this method will have wide applications in nano- and microscience and technologies.

  7. A note regarding the mathematical treatment of a class of steady-state compartmental models of the circulation.

    PubMed

    White, Ronald J

    2016-09-01

    A class of steady-state compartmental models of the circulation is examined and it is shown that the mathematical problem for this model class involves a single nonlinear equation. In an important subclass and with certain assumptions regarding the form of the Starling-type cardiac function curves, the single equation is of the form Z = μ + λ log[(1 - Z)/Z] where μ and λ are mathematical parameters related to the physiological parameters of the system and Z is proportional to the cardiac output. This result holds regardless of the number and arrangement of compartments within the model itself or of the number of physiological parameters the model contains. An example of this class with 25 physiological parameters is presented to illustrate this approach. PMID:27587712

  8. Molecular analysis reveals high compartmentalization in aphid-primary parasitoid networks and low parasitoid sharing between crop and noncrop habitats.

    PubMed

    Derocles, Stephane A P; Le Ralec, Anne; Besson, Mathilde M; Maret, Marion; Walton, Alan; Evans, Darren M; Plantegenest, Manuel

    2014-08-01

    The ecosystem service of insect pest regulation by natural enemies, such as primary parasitoids, may be enhanced by the presence of uncultivated, semi-natural habitats within agro-ecosystems, although quantifying such host-parasitoid interactions is difficult. Here, we use rRNA 16S gene sequencing to assess both the level of parasitism by Aphidiinae primary parasitoids and parasitoid identity on a large sample of aphids collected in cultivated and uncultivated agricultural habitats in Western France. We used these data to construct ecological networks to assess the level of compartmentalization between aphid and parasitoid food webs of cultivated and uncultivated habitats. We evaluated the extent to which uncultivated margins provided a resource for parasitoids shared between pest and nonpest aphids. We compared the observed quantitative ecological network described by our molecular approach to an empirical qualitative network based on aphid-parasitoid interactions from traditional rearing data found in the literature. We found that the molecular network was highly compartmentalized and that parasitoid sharing is relatively rare between aphids, especially between crop and noncrop compartments. Moreover, the few cases of putative shared generalist parasitoids were questionable and could be due to the lack of discrimination of cryptic species or from intraspecific host specialization. Our results suggest that apparent competition mediated by Aphidiinae parasitoids is probably rare in agricultural areas and that the contribution of field margins as a source of these biocontrol agents is much more limited than expected. Further large-scale (spatial and temporal) studies on other crops and noncrop habitats are needed to confirm this.

  9. Lipid Droplet-Associated Proteins (LDAPs) Are Required for the Dynamic Regulation of Neutral Lipid Compartmentation in Plant Cells.

    PubMed

    Gidda, Satinder K; Park, Sunjung; Pyc, Michal; Yurchenko, Olga; Cai, Yingqi; Wu, Peng; Andrews, David W; Chapman, Kent D; Dyer, John M; Mullen, Robert T

    2016-04-01

    Eukaryotic cells compartmentalize neutral lipids into organelles called lipid droplets (LDs), and while much is known about the role of LDs in storing triacylglycerols in seeds, their biogenesis and function in nonseed tissues are poorly understood. Recently, we identified a class of plant-specific, lipid droplet-associated proteins (LDAPs) that are abundant components of LDs in nonseed cell types. Here, we characterized the three LDAPs in Arabidopsis (Arabidopsis thaliana) to gain insight to their targeting, assembly, and influence on LD function and dynamics. While all three LDAPs targeted specifically to the LD surface, truncation analysis of LDAP3 revealed that essentially the entire protein was required for LD localization. The association of LDAP3 with LDs was detergent sensitive, but the protein bound with similar affinity to synthetic liposomes of various phospholipid compositions, suggesting that other factors contributed to targeting specificity. Investigation of LD dynamics in leaves revealed that LD abundance was modulated during the diurnal cycle, and characterization of LDAP misexpression mutants indicated that all three LDAPs were important for this process. LD abundance was increased significantly during abiotic stress, and characterization of mutant lines revealed that LDAP1 and LDAP3 were required for the proper induction of LDs during heat and cold temperature stress, respectively. Furthermore, LDAP1 was required for proper neutral lipid compartmentalization and triacylglycerol degradation during postgerminative growth. Taken together, these studies reveal that LDAPs are required for the maintenance and regulation of LDs in plant cells and perform nonredundant functions in various physiological contexts, including stress response and postgerminative growth. PMID:26896396

  10. Compartmentalized expression of light-induced clock genes in the suprachiasmatic nucleus of the diurnal grass rat (Arvicanthis niloticus)

    PubMed Central

    Ramanathan, Chidambaram; Campbell, Amy; Tomczak, Ashley; Nunez, Antonio A.; Smale, Laura; Yan, Lily

    2009-01-01

    Photic responses of the circadian system are mediated through light-induced clock gene expression in the suprachiasmatic nucleus (SCN). In nocturnal rodents, depending on the timing of light exposure, Per1 and Per2 gene expression shows distinct compartmentalized patterns that correspond to the behavioral responses. Whether the gene-and region-specific induction patterns are unique to nocturnal animals, or are also present in diurnal species is unknown. We explored this question by examining the light-induced Per1 and Per2 gene expression in functionally distinct SCN sub regions, using diurnal grass rats Arvicanthis niloticus. Light exposure during nighttime induced Per1 and Per2 expression in the SCN, showing unique spatiotemporal profiles depending on the phase of the light exposure. After a phase delaying light pulse (LP) in the early night, strong Per1 induction was observed in the retinorecipient core region of the SCN, while strong Per2 induction was observed throughout the entire SCN. After a phase advancing LP in the late night, Per1 was first induced in the core and then extended into the whole SCN, accompanied by a weak Per2 induction. This compartmentalized expression pattern is very similar to that observed in nocturnal rodents, suggesting that the same molecular and intercellular pathways underlying acute photic responses are present in both diurnal and nocturnal species. However, after a LP in early subjective day, which induces phase advances in diurnal grass rats, but not in nocturnal rodents, we did not observe any Per1 or Per2 induction in the SCN. This result suggests that in spite of remarkable similarities in the SCN of diurnal and nocturnal rodents, unique mechanisms are involved in mediating the phase shifts of diurnal animals during the subjective day. PMID:19393297

  11. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport.

    PubMed Central

    Rebouche, C J; Engel, A G

    1984-01-01

    The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-[methyl-3H]carnitine was administered intravenously to six normal subjects, one patient with primary muscle carnitine deficiency (MCD), and four patients with primary systemic carnitine deficiency (SCD). Specific radioactivity was followed in plasma for 28 d. A three-compartment model (extracellular fluid, muscle, and "other tissues") was adopted. Rate constants, fluxes, pool sizes, and turnover times were calculated. Results of these calculations indicated reduced transport of carnitine into muscle in both forms of primary carnitine deficiency. However, in SCD, the reduced rate of carnitine transport was attributed to reduced plasma carnitine concentration. In MCD, the results are consistent with an intrinsic defect in the transport process. Abnormal fluctuations of the plasma carnitine, but of a different form, occurred in MCD and SCD. The significance of these are unclear, but in SCD they suggest abnormal regulation of the muscle/plasma carnitine concentration gradient. In 8 of 11 subjects, carnitine excretion was less than dietary carnitine intake. Carnitine excretion rates calculated by kinetic compartmental analysis were higher than corresponding rates measured directly, indicating degradation of carnitine. However, we found no radioactive metabolites of L-[methyl-3H]carnitine in urine. These observations suggest that dietary carnitine was metabolized in the gastrointestinal tract. PMID:6707204

  12. Proline betaine accumulation and metabolism in alfalfa plants under sodium chloride stress. Exploring its compartmentalization in nodules.

    PubMed

    Trinchant, Jean-Charles; Boscari, Alexandre; Spennato, Guillaume; Van de Sype, Ghislaine; Le Rudulier, Daniel

    2004-07-01

    The osmoprotectant Pro betaine is the main betaine identified in alfalfa (Medicago sativa). We have investigated the long-term responses of nodulated alfalfa plants to salt stress, with a particular interest for Pro betaine accumulation, compartmentalization, and metabolism. Exposure of 3-week-old nodulated alfalfa plants to 0.2 m NaCl for 4 weeks was followed by a 10-, 4-, and 8-fold increase in Pro betaine in shoots, roots, and nodules, respectively. Isotope-labeling studies in alfalfa shoots indicate that [14C]Pro betaine was synthesized from l-[14C]Pro. [14C]Pro betaine was efficiently catabolized through sequential demethylations via N-methylPro and Pro. Salt stress had a minor effect on Pro betaine biosynthesis, whereas it strongly reduced Pro betaine turnover. Analysis of Pro betaine and Pro compartmentalization within nodules revealed that 4 weeks of salinization of the host plants induced a strong increase in cytosol and bacteroids. The estimated Pro betaine and Pro concentrations in salt-stressed bacteroids reached 7.4 and 11.8 mm, respectively, compared to only 0.8 mm in control bacteroids. Na+ content in nodule compartments was also enhanced under salinization, leading to a concentration of 14.7 mm in bacteroids. [14C]Pro betaine and [14C]Pro were taken up by purified symbiosomes and free bacteroids. There was no indication of saturable carrier(s), and the rate of uptake was moderately enhanced by salinization. Ultrastructural analysis showed a large peribacteroid space in salt-stressed nodules, suggesting an increased turgor pressure inside the symbiosomes, which might partially be due to an elevated concentration in Pro, Pro betaine, and Na+ in this compartment.

  13. Correlation between CD4 T cell Counts and Virus Compartmentalization in Genital and Systemic Compartments of HIV-infected Females

    PubMed Central

    Chaudhary, Suman; Noel, Richard J.; Rodríguez, Nayra; Collado, Santiago; Munoz, Jhoanne; Kumar, Anil; Yamamura, Yashuhiro

    2011-01-01

    The majority of infection by the human immunodeficiency virus (HIV-1) across the world occurs by heterosexual transmission and is likely mediated by virus present in genital secretions. In spite of this, infection is followed by clinical markers of the virus present in blood, which may not be representative of the virus involved in transmission. In fact, several studies have demonstrated that the genital tract represents a unique compartment for the virus. We assessed the relationship between immune system integrity, represented by CD4+ T cell counts, and the maintenance of viral compartmentalization between plasma and vaginal fluid virus in treatment naïve women from the Dominican Republic infected by the heterosexual transmission route. We cloned and sequenced cell free virus from plasma and genital fluid samples from six women to assess viral evolution, phylogenetic relatedness, and calculated co-receptor use for the C2V3 region of the envelope. Our analyses demonstrated plasma and vaginal fluid virus compartments remained intact only in samples from women with CD4+ T cell counts over 350 cells/μ1 majority of viral forms were predicted to use the CCR5 co-receptor, although several dual tropic forms were also identified. None of the clones were found to use the CXCR4 co-receptor even though many of the patients showed severe disease. Our findings lend further support to the role of an intact immune system in maintaining compartmentalization across blood and genital quasispecies and provide a compelling rationale to specifically consider genital tract viral forms in therapeutic and vaccine research. PMID:21745672

  14. Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs

    PubMed Central

    Li, Jane; Smith, Corey; Edwards, Jarem; Sierro, Frederic; Feng, Carl G.; Khanna, Rajiv; Bell, Andrew; Hislop, Andrew D.; Tangye, Stuart G.; Rickinson, Alan B.; Gebhardt, Thomas; Britton, Warwick J.

    2016-01-01

    Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103—, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections. PMID:27540722

  15. Nuclear Medicine

    MedlinePlus

    ... Parents/Teachers Resource Links for Students Glossary Nuclear Medicine What is nuclear medicine? What are radioactive tracers? ... funded researchers advancing nuclear medicine? What is nuclear medicine? Nuclear medicine is a medical specialty that uses ...

  16. Compartmentalized microchannel array for high-throughput analysis of single cell polarized growth and dynamics

    PubMed Central

    Geng, Tao; Bredeweg, Erin L.; Szymanski, Craig J.; Liu, Bingwen; Baker, Scott E.; Orr, Galya; Evans, James E.; Kelly, Ryan T.

    2015-01-01

    Interrogating polarized growth is technologically challenging due to extensive cellular branching and uncontrollable environmental conditions in conventional assays. Here we present a robust and high-performance microfluidic system that enables observations of polarized growth with enhanced temporal and spatial control over prolonged periods. The system has built-in tunability and versatility to accommodate a variety of scientific applications requiring precisely controlled environments. Using the model filamentous fungus, Neurospora crassa, our microfluidic system enabled direct visualization and analysis of cellular heterogeneity in a clonal fungal cell population, nuclear distribution and dynamics at the subhyphal level, and quantitative dynamics of gene expression with single hyphal compartment resolution in response to carbon source starvation and exchange. Although the microfluidic device is demonstrated on filamentous fungi, the technology is immediately extensible to a wide array of other biosystems that exhibit similar polarized cell growth, with applications ranging from bioenergy production to human health. PMID:26530004

  17. Compartmentalized microchannel array for high-throughput analysis of single cell polarized growth and dynamics

    DOE PAGES

    Geng, Tao; Bredeweg, Erin L.; Szymanski, Craig J.; Liu, Bingwen; Baker, Scott E.; Orr, Galya; Evans, James E.; Kelly, Ryan T.

    2015-11-04

    Here, interrogating polarized growth is technologically challenging due to extensive cellular branching and uncontrollable environmental conditions in conventional assays. Here we present a robust and high-performance microfluidic system that enables observations of polarized growth with enhanced temporal and spatial control over prolonged periods. The system has built-in tunability and versatility to accommodate a variety of science applications requiring precisely controlled environments. Using the model filamentous fungus, Neurospora crassa, this microfluidic system enabled direct visualization and analysis of cellular heterogeneity in a clonal fungal cell population, nuclear distribution and dynamics at the subhyphal level, and quantitative dynamics of gene expression withmore » single hyphal compartment resolution in response to carbon source starvation and exchange experiments. Although the microfluidic device is demonstrated on filamentous fungi, our technology is immediately extensible to a wide array of other biosystems that exhibit similar polarized cell growth with applications ranging from bioenergy production to human health.« less

  18. Compartmentalized microchannel array for high-throughput analysis of single cell polarized growth and dynamics

    SciTech Connect

    Geng, Tao; Bredeweg, Erin L.; Szymanski, Craig J.; Liu, Bingwen; Baker, Scott E.; Orr, Galya; Evans, James E.; Kelly, Ryan T.

    2015-11-04

    Here, interrogating polarized growth is technologically challenging due to extensive cellular branching and uncontrollable environmental conditions in conventional assays. Here we present a robust and high-performance microfluidic system that enables observations of polarized growth with enhanced temporal and spatial control over prolonged periods. The system has built-in tunability and versatility to accommodate a variety of science applications requiring precisely controlled environments. Using the model filamentous fungus, Neurospora crassa, this microfluidic system enabled direct visualization and analysis of cellular heterogeneity in a clonal fungal cell population, nuclear distribution and dynamics at the subhyphal level, and quantitative dynamics of gene expression with single hyphal compartment resolution in response to carbon source starvation and exchange experiments. Although the microfluidic device is demonstrated on filamentous fungi, our technology is immediately extensible to a wide array of other biosystems that exhibit similar polarized cell growth with applications ranging from bioenergy production to human health.

  19. The conformational and subcellular compartmental dance of plant NLRs during viral recognition and defense signaling

    PubMed Central

    Padmanabhan, Meenu S; Dinesh-Kumar, Savithramma P

    2014-01-01

    Plant innate immune response against viruses utilizes intracellular Nucleotide Binding domain Leucine Rich Repeat (NLR) class of receptors. NLRs recognize different viral proteins termed elicitors and initiate diverse signaling processes that induce programmed cell death (PCD) in infected cells and restrict virus spread. In this review we describe the recent advances made in the study of plant NLRs that detect viruses. We describe some of the physical and functional interactions these NLRs undertake. We elaborate on the intra-molecular and homotypic association of NLRs that function in self-regulation and activation. Nuclear role for some viral NLRs is discussed as well as the emerging importance of the RNAi pathway in regulating the NLR family. PMID:24906192

  20. Experimental infection of highly and low pathogenic avian influenza viruses to chickens, ducks, tree sparrows, jungle crows, and black rats for the evaluation of their roles in virus transmission.

    PubMed

    Hiono, Takahiro; Okamatsu, Masatoshi; Yamamoto, Naoki; Ogasawara, Kohei; Endo, Mayumi; Kuribayashi, Saya; Shichinohe, Shintaro; Motohashi, Yurie; Chu, Duc-Huy; Suzuki, Mizuho; Ichikawa, Takaya; Nishi, Tatsuya; Abe, Yuri; Matsuno, Keita; Tanaka, Kazuyuki; Tanigawa, Tsutomu; Kida, Hiroshi; Sakoda, Yoshihiro

    2016-01-01

    Highly pathogenic avian influenza viruses (HPAIVs) have spread in both poultry and wild birds. Determining transmission routes of these viruses during an outbreak is essential for the control of avian influenza. It has been widely postulated that migratory ducks play crucial roles in the widespread dissemination of HPAIVs in poultry by carrying viruses along with their migrations; however close contacts between wild migratory ducks and poultry are less likely in modern industrial poultry farming settings. Therefore, we conducted experimental infections of HPAIVs and low pathogenic avian influenza viruses (LPAIVs) to chickens, domestic ducks, tree sparrows, jungle crows, and black rats to evaluate their roles in virus transmission. The results showed that chickens, ducks, sparrows, and crows were highly susceptible to HPAIV infection. Significant titers of virus were recovered from the sparrows and crows infected with HPAIVs, which suggests that they potentially play roles of transmission of HPAIVs to poultry. In contrast, the growth of LPAIVs was limited in each of the animals tested compared with that of HPAIVs. The present results indicate that these common synanthropes play some roles in influenza virus transmission from wild birds to poultry.

  1. Experimental infection of highly and low pathogenic avian influenza viruses to chickens, ducks, tree sparrows, jungle crows, and black rats for the evaluation of their roles in virus transmission.

    PubMed

    Hiono, Takahiro; Okamatsu, Masatoshi; Yamamoto, Naoki; Ogasawara, Kohei; Endo, Mayumi; Kuribayashi, Saya; Shichinohe, Shintaro; Motohashi, Yurie; Chu, Duc-Huy; Suzuki, Mizuho; Ichikawa, Takaya; Nishi, Tatsuya; Abe, Yuri; Matsuno, Keita; Tanaka, Kazuyuki; Tanigawa, Tsutomu; Kida, Hiroshi; Sakoda, Yoshihiro

    2016-01-15

    Highly pathogenic avian influenza viruses (HPAIVs) have spread in both poultry and wild birds. Determining transmission routes of these viruses during an outbreak is essential for the control of avian influenza. It has been widely postulated that migratory ducks play crucial roles in the widespread dissemination of HPAIVs in poultry by carrying viruses along with their migrations; however close contacts between wild migratory ducks and poultry are less likely in modern industrial poultry farming settings. Therefore, we conducted experimental infections of HPAIVs and low pathogenic avian influenza viruses (LPAIVs) to chickens, domestic ducks, tree sparrows, jungle crows, and black rats to evaluate their roles in virus transmission. The results showed that chickens, ducks, sparrows, and crows were highly susceptible to HPAIV infection. Significant titers of virus were recovered from the sparrows and crows infected with HPAIVs, which suggests that they potentially play roles of transmission of HPAIVs to poultry. In contrast, the growth of LPAIVs was limited in each of the animals tested compared with that of HPAIVs. The present results indicate that these common synanthropes play some roles in influenza virus transmission from wild birds to poultry. PMID:26711036

  2. Two-compartmental population balance modeling of a pulsed spray fluidized bed granulation based on computational fluid dynamics (CFD) analysis.

    PubMed

    Liu, Huolong; Li, Mingzhong

    2014-11-20

    In this work a two-compartmental population balance model (TCPBM) was proposed to model a pulsed top-spray fluidized bed granulation. The proposed TCPBM considered the spatially heterogeneous granulation mechanisms of the granule growth by dividing the granulator into two perfectly mixed zones of the wetting compartment and drying compartment, in which the aggregation mechanism was assumed in the wetting compartment and the breakage mechanism was considered in the drying compartment. The sizes of the wetting and drying compartments were constant in the TCPBM, in which 30% of the bed was the wetting compartment and 70% of the bed was the drying compartment. The exchange rate of particles between the wetting and drying compartments was determined by the details of the flow properties and distribution of particles predicted by the computational fluid dynamics (CFD) simulation. The experimental validation has shown that the proposed TCPBM can predict evolution of the granule size and distribution within the granulator under different binder spray operating conditions accurately.

  3. Multi-compartmental biomaterial scaffolds for patterning neural tissue organoids in models of neurodevelopment and tissue regeneration

    PubMed Central

    McMurtrey, Richard J

    2016-01-01

    Biomaterials are becoming an essential tool in the study and application of stem cell research. Various types of biomaterials enable three-dimensional culture of stem cells, and, more recently, also enable high-resolution patterning and organization of multicellular architectures. Biomaterials also hold potential to provide many additional advantages over cell transplants alone in regenerative medicine. This article describes novel designs for functionalized biomaterial constructs that guide tissue development to targeted regional identities and structures. Such designs comprise compartmentalized regions in the biomaterial structure that are functionalized with molecular factors that form concentration gradients through the construct and guide stem cell development, axis patterning, and tissue architecture, including rostral/caudal, ventral/dorsal, or medial/lateral identities of the central nervous system. The ability to recapitulate innate developmental processes in a three-dimensional environment and under specific controlled conditions has vital application to advanced models of neurodevelopment and for repair of specific sites of damaged or diseased neural tissue. PMID:27766141

  4. Compartmentation of alpha 1 and alpha 2 GABA(A) receptor subunits within rat extended amygdala: implications for benzodiazepine action.

    PubMed

    Kaufmann, Walter A; Humpel, Christian; Alheid, George F; Marksteiner, Josef

    2003-02-21

    The extended amygdala, a morphological and functional entity within the basal forebrain, is a neuronal substrate for emotional states like fear and anxiety. Anxiety disorders are commonly treated by benzodiazepines that mediate their action via GABA(A) receptors. The binding properties and action of benzodiazepines depend on the alpha-subunit profile of the hetero-pentameric receptors: whereas the alpha1 subunit is associated with benzodiazepine type I pharmacology and reportedly mediates sedative as well as amnesic actions of benzodiazepines, the alpha2 subunit confers benzodiazepine type II pharmacology and mediates the anxiolytic actions of benzodiazepines. We determined the localization of alpha1 and alpha2 subunits within the extended amygdala, identified by secretoneurin immunostaining, to define the morphological substrates for the diverse benzodiazepine actions. A moderate expression of the alpha1 subunit could be detected in compartments of the medial subdivision and a strong expression of the alpha2 subunit throughout the central subdivision. It is concluded that the alpha1 and alpha2 subunits are differentially expressed within the extended amygdala, indicating that this structure is compartmentalized with respect to function and benzodiazepine action. PMID:12573516

  5. Differences in activation of mouse hepcidin by dietary iron and parenterally administered iron dextran: compartmentalization is critical for iron sensing.

    PubMed

    Daba, Alina; Gkouvatsos, Konstantinos; Sebastiani, Giada; Pantopoulos, Kostas

    2013-01-01

    The iron regulatory hormone hepcidin responds to both oral and parenteral iron. Here, we hypothesized that the diverse iron trafficking routes may affect the dynamics and kinetics of the hepcidin activation pathway. To address this, C57BL/6 mice were administered an iron-enriched diet or injected i.p. with iron dextran and analyzed over time. After 1 week of dietary loading with carbonyl iron, mice exhibited significant increases in serum iron and transferrin saturation, as well as in hepatic iron, Smad1/5/8 phosphorylation and bone morphogenetic protein 6 (BMP6), and hepcidin mRNAs. Nevertheless, hepcidin expression reached a plateau afterward, possibly due to upregulation of inhibitory Smad7, Id1, and matriptase-2 mRNAs, while hepatic and splenic iron continued to accumulate over 9 weeks. One day following parenteral administration of iron dextran, mice manifested elevated serum and hepatic iron levels and Smad1/5/8 phosphorylation, but no increases in transferrin saturation or BMP6 mRNA. Surprisingly, hepcidin failed to appropriately respond to acute overload with iron dextran, and a delayed (after 5-7 days) hepcidin upregulation correlated with increased transferrin saturation, partial relocation of iron from macrophages to hepatocytes, and induction of BMP6 mRNA. Our data suggest that the physiological hepcidin response is saturable and are consistent with the idea that hepcidin senses exclusively iron compartmentalized within circulating transferrin and/or hepatocytes.

  6. Compartmentalized energy transfer in cardiomyocytes: use of mathematical modeling for analysis of in vivo regulation of respiration.

    PubMed Central

    Aliev, M K; Saks, V A

    1997-01-01

    The mathematical model of the compartmentalized energy transfer system in cardiac myocytes presented includes mitochondrial synthesis of ATP by ATP synthase, phosphocreatine production in the coupled mitochondrial creatine kinase reaction, the myofibrillar and cytoplasmic creatine kinase reactions, ATP utilization by actomyosin ATPase during the contraction cycle, and diffusional exchange of metabolites between different compartments. The model was used to calculate the changes in metabolite profiles during the cardiac cycle, metabolite and energy fluxes in different cellular compartments at high workload (corresponding to the rate of oxygen consumption of 46 mu atoms of O.(g wet mass)-1.min-1) under varying conditions of restricted ADP diffusion across mitochondrial outer membrane and creatine kinase isoenzyme "switchoff." In the complete system, restricted diffusion of ADP across the outer mitochondrial membrane stabilizes phosphocreatine production in cardiac mitochondria and increases the role of the phosphocreatine shuttle in energy transport and respiration regulation. Selective inhibition of myoplasmic or mitochondrial creatine kinase (modeling the experiments with transgenic animals) results in "takeover" of their function by another, active creatine kinase isoenzyme. This mathematical modeling also shows that assumption of the creatine kinase equilibrium in the cell may only be a very rough approximation to the reality at increased workload. The mathematical model developed can be used as a basis for further quantitative analyses of energy fluxes in the cell and their regulation, particularly by adding modules for adenylate kinase, the glycolytic system, and other reactions of energy metabolism of the cell. Images FIGURE 7 FIGURE 2 FIGURE 7 PMID:9199806

  7. Simultaneous compartmentalization of lead and arsenic in co-hyperaccumulator Viola principis H. de Boiss.: an application of SRXRF microprobe.

    PubMed

    Lei, Mei; Chen, Tong-Bin; Huang, Ze-Chun; Wang, Yao-Dong; Huang, Yu-Ying

    2008-08-01

    The cellular distributions of Pb and As in the leaves of co-hyperaccumulator Viola principis H. de Boiss. were inspected by synchrotron X-ray fluorescence spectroscopy (SRXRF). The results revealed that Pb and As had similar compartmentalization patterns in the leaves. Both elements were enriched in the bundle sheath and the palisade mesophyll. In comparison with the sheath and the mesophyll, the vascular bundle and the epidermis contained lower levels of Pb and As. The palisade enrichment of Pb and As indicated that V. principis H. de Boiss. may have a special mechanism on detoxification of toxic metals within the mesophyll cells. Relative concentrations of both Pb and As in trichome bases were higher than those in trichome rays. The results of hierarchical cluster analysis and correlation analysis confirmed that the distribution of Pb was similar to that of As in the leaves, and their distribution patterns were different from the nutrient elements, such as K, Ca, Mn, Fe, Ni, Cu and Zn. In vivo cellular localization of Pb and As in the leaves provides insight into the physiological mechanisms of metal tolerance and hyperaccumulation in the hyperaccumulators.

  8. Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues.

    PubMed

    Thome, Joseph J C; Bickham, Kara L; Ohmura, Yoshiaki; Kubota, Masaru; Matsuoka, Nobuhide; Gordon, Claire; Granot, Tomer; Griesemer, Adam; Lerner, Harvey; Kato, Tomoaki; Farber, Donna L

    2016-01-01

    It is unclear how the immune response in early life becomes appropriately stimulated to provide protection while also avoiding excessive activation as a result of diverse new antigens. T cells are integral to adaptive immunity; mouse studies indicate that tissue localization of T cell subsets is important for both protective immunity and immunoregulation. In humans, however, the early development and function of T cells in tissues remain unexplored. We present here an analysis of lymphoid and mucosal tissue T cells derived from pediatric organ donors in the first two years of life, as compared to adult organ donors, revealing early compartmentalization of T cell differentiation and regulation. Whereas adult tissues contain a predominance of memory T cells, in pediatric blood and tissues the main subset consists of naive recent thymic emigrants, with effector memory T cells (T(EM)) found only in the lungs and small intestine. Additionally, regulatory T (T(reg)) cells comprise a high proportion (30-40%) of CD4(+) T cells in pediatric tissues but are present at much lower frequencies (1-10%) in adult tissues. Pediatric tissue T(reg) cells suppress endogenous T cell activation, and early T cell functionality is confined to the mucosal sites that have the lowest T(reg):T(EM) cell ratios, which suggests control in situ of immune responses in early life. PMID:26657141

  9. The paraveinal mesophyll of soybean leaves in relation to assimilate transfer and compartmentation : I. Ultrastructure and histochemistry during vegetative development.

    PubMed

    Franceschi, V R; Giaquinta, R T

    1983-04-01

    The paraveinal mesophyll (PVM) is a unique and specialized, one-cell-thick tissue spanning the vascular bundles at the level of the phloem in soybean (Glycine max) (L.) Merr.) leaves. Its position within the leaf dictates that all photosynthate produced in the palisade and spongy mesophyll must pass through this specialized layer enroute to the phloem. Symplastic continuity, via plasmodesmata, exists between the PVM and bundle sheath, palisade parenchyma and spongy mesophyll. During leaf ontogeny the PVM is the first tissue to differentiate and at maturity these cells are six to eight times larger than other mesophyll cells, are highly vacuolate, and are interconnected by tubular arms. The PVM undergoes several unique structural and metabolic modifications during leaf development. The PVM cytoplasm, in vegetative plants, is dense, enriched in rough endoplasmic reticulum and dictyosomes, but contains few, small starch-free chloroplasts and few microbodies. Unlike the tonoplast of mesophyll cells, the tonoplast of the PVM is unusually thick and dense-staining. During leaf development the vacuoles of PVM cells accumulate a glycoprotein derived from the dictyosomes which reacts with the protein staining reagents, mercuric bromophenol blue and sulfaflavine, and is degraded by Pronase. Both the vacuolar material and tonoplast are also stained by phosphotungstic acid, which at low pH is relatively selective for glycoprotein. A unique role of the PVM in the transport and compartmentation of nitrogen reserves in soybeans is discussed.

  10. Spatial Phosphoprotein Profiling Reveals a Compartmentalized Extracellular Signal-regulated Kinase Switch Governing Neurite Growth and Retraction

    SciTech Connect

    Wang, Yingchun; Yang, Feng; Fu, Yi; Huang, Xiahe; Wang, Wei; Jiang, Xining; Gritsenko, Marina A.; Zhao, Rui; Monroe, Matthew E.; Pertz, Olivier C.; Purvine, Samuel O.; Orton, Daniel J.; Jacobs, Jon M.; Camp, David G.; Smith, Richard D.; Klemke, Richard L.

    2011-05-20

    Abstract - Brain development and spinal cord regeneration require neurite sprouting and growth cone navigation in response to extension and collapsing factors present in the extracellular environment. These external guidance cues control neurite growth cone extension and retraction processes through intracellular protein phosphorylation of numerous cytoskeletal, adhesion, and polarity complex signaling proteins. However, the complex kinase/substrate signaling networks that mediate neuritogenesis have not been investigated. Here, we compare the neurite phosphoproteome under growth and retraction conditions using neurite purification methodology combined with mass spectrometry. More than 4000 non-redundant phosphorylation sites from 1883 proteins have been annotated and mapped to signaling pathways that control kinase/phosphatase networks, cytoskeleton remodeling, and axon/dendrite specification. Comprehensive informatics and functional studies revealed a compartmentalized ERK activation/deactivation cytoskeletal switch that governs neurite growth and retraction, respectively. Our findings provide the first system-wide analysis of the phosphoprotein signaling networks that enable neurite growth and retraction and reveal an important molecular switch that governs neuritogenesis.

  11. Surface interactions with compartmentalized cellular phosphates explain rare earth oxide nanoparticle hazard and provide opportunities for safer design.

    PubMed

    Li, Ruibin; Ji, Zhaoxia; Chang, Chong Hyun; Dunphy, Darren R; Cai, Xiaoming; Meng, Huan; Zhang, Haiyuan; Sun, Bingbing; Wang, Xiang; Dong, Juyao; Lin, Sijie; Wang, Meiying; Liao, Yu-Pei; Brinker, C Jeffrey; Nel, Andre; Xia, Tian

    2014-02-25

    Growing international exploitation of rare earth oxides (REOs) for commercial and biological use has increased the possibility of human exposure and adverse health effects. Occupational exposure to rare earth materials in miners and polishers leads to a severe form of pneumoconiosis, while gadolinium-containing MRI contrast agents cause nephrogenic systemic fibrosis in patients with renal impairment. The mechanisms for inducing these adverse pro-fibrogenic effects are of considerable importance for the safety assessment of REO particles as well as presenting opportunities for safer design. In this study, using a well-prepared REO library, we obtained a mechanistic understanding of how REOs induce cellular and pulmonary damage by a compartmentalized intracellular biotransformation process in lysosomes that results in pro-fibrogenic growth factor production and lung fibrosis. We demonstrate that rare earth oxide ion shedding in acidifying macrophage lysosomes leads to biotic phosphate complexation that results in organelle damage due to stripping of phosphates from the surrounding lipid bilayer. This results in nanoparticle biotransformation into urchin shaped structures and setting in motion a series of events that trigger NLRP3 inflammasome activation, IL-1β release, TGF-β1 and PDGF-AA production. However, pretreatment of REO nanoparticles with phosphate in a neutral pH environment prevents biological transformation and pro-fibrogenic effects. This can be used as a safer design principle for producing rare earth nanoparticles for biological use.

  12. Lipid droplet-associated proteins (LDAPs) are involved in the compartmentalization of lipophilic compounds in plant cells.

    PubMed

    Gidda, Satinder K; Watt, Samantha; Collins-Silva, Jillian; Kilaru, Aruna; Arondel, Vincent; Yurchenko, Olga; Horn, Patrick J; James, Christopher N; Shintani, David; Ohlrogge, John B; Chapman, Kent D; Mullen, Robert T; Dyer, John M

    2013-11-01

    While lipid droplets have traditionally been considered as inert sites for the storage of triacylglycerols and sterol esters, they are now recognized as dynamic and functionally diverse organelles involved in energy homeostasis, lipid signaling, and stress responses. Unlike most other organelles, lipid droplets are delineated by a half-unit membrane whose protein constituents are poorly understood, except in the specialized case of oleosins, which are associated with seed lipid droplets. Recently, we identified a new class of lipid-droplet associated proteins called LDAPs that localize specifically to the lipid droplet surface within plant cells and share extensive sequence similarity with the small rubber particle proteins (SRPPs) found in rubber-accumulating plants. Here, we provide additional evidence for a role of LDAPs in lipid accumulation in oil-rich fruit tissues, and further explore the functional relationships between LDAPs and SRPPs. In addition, we propose that the larger LDAP/SRPP protein family plays important roles in the compartmentalization of lipophilic compounds, including triacylglycerols and polyisoprenoids, into lipid droplets within plant cells. Potential roles in lipid droplet biogenesis and function of these proteins also are discussed. PMID:24305619

  13. Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues.

    PubMed

    Thome, Joseph J C; Bickham, Kara L; Ohmura, Yoshiaki; Kubota, Masaru; Matsuoka, Nobuhide; Gordon, Claire; Granot, Tomer; Griesemer, Adam; Lerner, Harvey; Kato, Tomoaki; Farber, Donna L

    2016-01-01

    It is unclear how the immune response in early life becomes appropriately stimulated to provide protection while also avoiding excessive activation as a result of diverse new antigens. T cells are integral to adaptive immunity; mouse studies indicate that tissue localization of T cell subsets is important for both protective immunity and immunoregulation. In humans, however, the early development and function of T cells in tissues remain unexplored. We present here an analysis of lymphoid and mucosal tissue T cells derived from pediatric organ donors in the first two years of life, as compared to adult organ donors, revealing early compartmentalization of T cell differentiation and regulation. Whereas adult tissues contain a predominance of memory T cells, in pediatric blood and tissues the main subset consists of naive recent thymic emigrants, with effector memory T cells (T(EM)) found only in the lungs and small intestine. Additionally, regulatory T (T(reg)) cells comprise a high proportion (30-40%) of CD4(+) T cells in pediatric tissues but are present at much lower frequencies (1-10%) in adult tissues. Pediatric tissue T(reg) cells suppress endogenous T cell activation, and early T cell functionality is confined to the mucosal sites that have the lowest T(reg):T(EM) cell ratios, which suggests control in situ of immune responses in early life.

  14. Surface Interactions with Compartmentalized Cellular Phosphates Explain Rare Earth Oxide Nanoparticle Hazard and Provide Opportunities for Safer Design

    PubMed Central

    2014-01-01

    Growing international exploitation of rare earth oxides (REOs) for commercial and biological use has increased the possibility of human exposure and adverse health effects. Occupational exposure to rare earth materials in miners and polishers leads to a severe form of pneumoconiosis, while gadolinium-containing MRI contrast agents cause nephrogenic systemic fibrosis in patients with renal impairment. The mechanisms for inducing these adverse pro-fibrogenic effects are of considerable importance for the safety assessment of REO particles as well as presenting opportunities for safer design. In this study, using a well-prepared REO library, we obtained a mechanistic understanding of how REOs induce cellular and pulmonary damage by a compartmentalized intracellular biotransformation process in lysosomes that results in pro-fibrogenic growth factor production and lung fibrosis. We demonstrate that rare earth oxide ion shedding in acidifying macrophage lysosomes leads to biotic phosphate complexation that results in organelle damage due to stripping of phosphates from the surrounding lipid bilayer. This results in nanoparticle biotransformation into urchin shaped structures and setting in motion a series of events that trigger NLRP3 inflammasome activation, IL-1β release, TGF-β1 and PDGF-AA production. However, pretreatment of REO nanoparticles with phosphate in a neutral pH environment prevents biological transformation and pro-fibrogenic effects. This can be used as a safer design principle for producing rare earth nanoparticles for biological use. PMID:24417322

  15. Lipid droplet-associated proteins (LDAPs) are involved in the compartmentalization of lipophilic compounds in plant cells.

    PubMed

    Gidda, Satinder K; Watt, Samantha; Collins-Silva, Jillian; Kilaru, Aruna; Arondel, Vincent; Yurchenko, Olga; Horn, Patrick J; James, Christopher N; Shintani, David; Ohlrogge, John B; Chapman, Kent D; Mullen, Robert T; Dyer, John M

    2013-11-01

    While lipid droplets have traditionally been considered as inert sites for the storage of triacylglycerols and sterol esters, they are now recognized as dynamic and functionally diverse organelles involved in energy homeostasis, lipid signaling, and stress responses. Unlike most other organelles, lipid droplets are delineated by a half-unit membrane whose protein constituents are poorly understood, except in the specialized case of oleosins, which are associated with seed lipid droplets. Recently, we identified a new class of lipid-droplet associated proteins called LDAPs that localize specifically to the lipid droplet surface within plant cells and share extensive sequence similarity with the small rubber particle proteins (SRPPs) found in rubber-accumulating plants. Here, we provide additional evidence for a role of LDAPs in lipid accumulation in oil-rich fruit tissues, and further explore the functional relationships between LDAPs and SRPPs. In addition, we propose that the larger LDAP/SRPP protein family plays important roles in the compartmentalization of lipophilic compounds, including triacylglycerols and polyisoprenoids, into lipid droplets within plant cells. Potential roles in lipid droplet biogenesis and function of these proteins also are discussed.

  16. Influence of nonequilibrium lipid transport, membrane compartmentalization, and membrane proteins on the lateral organization of the plasma membrane

    NASA Astrophysics Data System (ADS)

    Fan, Jun; Sammalkorpi, Maria; Haataja, Mikko

    2010-01-01

    Compositional lipid domains (lipid rafts) in plasma membranes are believed to be important components of many cellular processes. The mechanisms by which cells regulate the sizes, lifetimes, and spatial localization of these domains are rather poorly understood at the moment. We propose a robust mechanism for the formation of finite-sized lipid raft domains in plasma membranes, the competition between phase separation in an immiscible lipid system and active cellular lipid transport processes naturally leads to the formation of such domains. Simulations of a continuum model reveal that the raft size distribution is broad and the average raft size is strongly dependent on the rates of cellular and interlayer lipid transport processes. We demonstrate that spatiotemporal variations in the recycling may enable the cell to localize larger raft aggregates at specific parts along the membrane. Moreover, we show that membrane compartmentalization may further facilitate spatial localization of the raft domains. Finally, we demonstrate that local interactions with immobile membrane proteins can spatially localize the rafts and lead to further clustering.

  17. Two-compartmental population balance modeling of a pulsed spray fluidized bed granulation based on computational fluid dynamics (CFD) analysis.

    PubMed

    Liu, Huolong; Li, Mingzhong

    2014-11-20

    In this work a two-compartmental population balance model (TCPBM) was proposed to model a pulsed top-spray fluidized bed granulation. The proposed TCPBM considered the spatially heterogeneous granulation mechanisms of the granule growth by dividing the granulator into two perfectly mixed zones of the wetting compartment and drying compartment, in which the aggregation mechanism was assumed in the wetting compartment and the breakage mechanism was considered in the drying compartment. The sizes of the wetting and drying compartments were constant in the TCPBM, in which 30% of the bed was the wetting compartment and 70% of the bed was the drying compartment. The exchange rate of particles between the wetting and drying compartments was determined by the details of the flow properties and distribution of particles predicted by the computational fluid dynamics (CFD) simulation. The experimental validation has shown that the proposed TCPBM can predict evolution of the granule size and distribution within the granulator under different binder spray operating conditions accurately. PMID:25181553

  18. Tissue Level Compartmentation of (R)-Amygdalin and Amygdalin Hydrolase Prevents Large-Scale Cyanogenesis in Undamaged Prunus Seeds.

    PubMed

    Poulton, J. E.; Li, C. P.

    1994-01-01

    Plum (Prunus domestica) seeds, which contain the cyanogenic diglucoside (R)-amygdalin and lesser amounts of the corresponding monoglucoside (R)-prunasin, release the respiratory toxin HCN upon tissue disruption. Amygdalin hydrolase (AH) and prunasin hydrolase (PH), two specific [beta]-glucosidases responsible for hydrolysis of these glucosides, were purified to near homogeneity by concanavalin A-Sepharose 4B and carboxymethyl-cellulose chromatography. Both proteins appear as polypeptides with molecular masses of 60 kD upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but they exhibit different isoelectric points (PH, 5.6-6.0; AH, 7.8-8.2). AH and PH were localized within mature plum seeds by tissue printing, histochemistry, and silver-enhanced immunogold labeling. As was previously shown in black cherry (Prunus serotina) seeds (E.Swain, C.P. Li, J.E. Poulton [1992] Plant Physiol 100: 291-300), AH and PH are restricted to protein bodies of specific procambial cells and are absent from the cotyledonary parenchyma, bundle sheath, and endosperm cells. In contrast, the cyanogenic glycosides in both plum and black cherry seeds, which were detected by tissue printing, occur solely in the cotyledonary parenchyma and are absent from the procambium and endosperm. It is concluded that tissue level compartmentation prevents large-scale cyanoglycoside hydrolysis in intact Prunus seeds. PMID:12232058

  19. The F-BAR protein Cip4/Toca-1 antagonizes the formin Diaphanous in membrane stabilization and compartmentalization

    PubMed Central

    Yan, Shuling; Lv, Zhiyi; Winterhoff, Moritz; Wenzl, Christian; Zobel, Thomas; Faix, Jan; Bogdan, Sven; Grosshans, Jörg

    2013-01-01

    Summary During Drosophila embryogenesis, the first epithelium with defined cortical compartments is established during cellularization. Actin polymerization is required for the separation of lateral and basal domains as well as suppression of tubular extensions in the basal domain. The actin nucleator mediating this function is unknown. We found that the formin Diaphanous (Dia) is required for establishing and maintaining distinct lateral and basal domains during cellularization. In dia mutant embryos lateral marker proteins, such as Discs-large and Armadillo/β-Catenin spread into the basal compartment. Furthermore, high-resolution and live-imaging analysis of dia mutant embryos revealed an increased number of membrane extensions and endocytic activity at the basal domain, indicating a suppressing function of dia on membrane invaginations. Dia function might be based on an antagonistic interaction with the F-BAR protein Cip4/Toca-1, a known activator of the WASP/WAVE-Arp2/3 pathway. Dia and Cip4 physically and functionally interact and overexpression of Cip4 phenocopies dia loss-of-function. In vitro, Cip4 inhibits mainly actin nucleation by Dia. Thus, our data support a model in which linear actin filaments induced by Dia stabilize cortical compartmentalization by antagonizing membrane turnover induced by WASP/WAVE-Arp2/3. PMID:23424199

  20. Compartmentation of Nucleotides in Corn Root Tips Studied by 31P-NMR and HPLC 1

    PubMed Central

    Hooks, Mark A.; Clark, Robert A.; Nieman, Richard H.; Roberts, Justin K. M.

    1989-01-01

    Corn (Zea mays L.) root tips were subjected to different conditions so that nucleotide levels varied over a wide range. Levels of nucleotides in corn root tips were measured using 31P nuclear magnetic resonance (NMR) spectroscopy and high performance liquid chromatography. Results indicate: (a) Similar amounts of NTP and sugar nucleotides were observed by in vivo NMR and in extracts. In contrast, a significant amount of NDP observed in root tip extracts was not detected by in vivo NMR. Thus, for a given sample, [NTP]/[NDP] ratios determined in vivo by 31P-NMR are always higher than ratios observed in extracts, deviating by ∼4-fold at the highest ratios. The NMR-invisible pool of NDP appeared quite metabolically inert, barely changing in size as total cell NDP changed. We conclude that NDP in corn root tips is compartmented with respect to NMR visibility, and that it is the NMR-visible pool which responds dynamically to metabolic state. The NMR-invisible NDP could either be immobilized (and so have broad, undetectable NMR signals), or be complexed with species that cause the chemical shift of NDP to change (so it does not contribute to the NMR signal of free NDP), or both. (b) 31P-NMR cannot distinguish between bases (A, U, C, and G) of nucleotides. HPLC analysis of root tip extracts showed that the relative amount of each base in the NTP and NDP pools was quite constant in the different samples. (c) In extracts, for each of the nonadenylate nucleotides, [NTP]/[NDP] was linearly proportional to [ATP]/[ADP], indicating near equilibrium in the nucleoside diphosphokinase (NDPK) reaction. However, the apparent equilibrium constants for the phosphorylation of GDP and UDP by ATP were significantly lower than 1, the true equilibrium constant for the NDPK reaction. Thus, for a given sample, [ATP]/[ADP] ∼ [CTP]/[CDP] > [UTP]/[UDP] > [GTP]/[GDP]. This result suggests that the different NDPs in corn root tips do not have equal access to NDPK. PMID:16666649

  1. Is the Dissociative Experiences Scale able to identify detachment and compartmentalization symptoms? Factor structure of the Dissociative Experiences Scale in a large sample of psychiatric and nonpsychiatric subjects

    PubMed Central

    Mazzotti, Eva; Farina, Benedetto; Imperatori, Claudio; Mansutti, Federica; Prunetti, Elena; Speranza, Anna Maria; Barbaranelli, Claudio

    2016-01-01

    Background In this study, we explored the ability of the Dissociative Experiences Scale (DES) to catch detachment and compartmentalization symptoms. Participants and methods The DES factor structure was evaluated in 768 psychiatric patients (546 women and 222 men) and in 2,403 subjects enrolled in nonpsychiatric settings (1,857 women and 546 men). All participants were administered the Italian version of DES. Twenty senior psychiatric experts in the treatment of dissociative symptoms independently assessed the DES items and categorized each of them as follows: “C” for compartmentalization, “D” for detachment, and “NC” for noncongruence with either C or D. Results Confirmatory factor analysis supported the three-factor structure of DES in both clinical and nonclinical samples and its invariance across the two groups. Moreover, factor analyses results overlapped with those from the expert classification procedure. Conclusion Our results showed that DES can be used as a valid instrument for clinicians to assess the frequency of different types of dissociative experiences including detachment and compartmentalization. PMID:27350746

  2. Nucleolus: the fascinating nuclear body

    PubMed Central

    Sirri, Valentina; Urcuqui-Inchima, Silvio; Roussel, Pascal

    2007-01-01

    Nucleoli are the prominent contrasted structures of the cell nucleus. In the nucleolus, ribosomal RNAs are synthesized, processed and assembled with ribosomal proteins. RNA polymerase I synthesizes the ribosomal RNAs and this activity is cell cycle regulated. The nucleolus reveals the functional organization of the nucleus in which the compartmentation of the different steps of ribosome biogenesis is observed whereas the nucleolar machineries are in permanent exchange with the nucleoplasm and other nuclear bodies. After mitosis, nucleolar assembly is a time and space regulated process controlled by the cell cycle. In addition, by generating a large volume in the nucleus with apparently no RNA polymerase II activity, the nucleolus creates a domain of retention/sequestration of molecules normally active outside the nucleolus. Viruses interact with the nucleolus and recruit nucleolar proteins to facilitate virus replication. The nucleolus is also a sensor of stress due to the redistribution of the ribosomal proteins in the nucleoplasm by nucleolus disruption. The nucleolus plays several crucial functions in the nucleus: in addition to its function as ribosome factory of the cells it is a multifunctional nuclear domain, and nucleolar activity is linked with several pathologies. Perspectives on the evolution of this research area are proposed. PMID:18046571

  3. Nuclear rights - nuclear wrongs

    SciTech Connect

    Paul, E.F.; Miller, F.D.; Paul, J.; Ahrens, J.

    1986-01-01

    This book contains 11 selections. The titles are: Three Ways to Kill Innocent Bystanders: Some Conundrums Concerning the Morality of War; The International Defense of Liberty; Two Concepts of Deterrence; Nuclear Deterrence and Arms Control; Ethical Issues for the 1980s; The Moral Status of Nuclear Deterrent Threats; Optimal Deterrence; Morality and Paradoxical Deterrence; Immoral Risks: A Deontological Critique of Nuclear Deterrence; No War Without Dictatorship, No Peace Without Democracy: Foreign Policy as Domestic Politics; Marxism-Leninism and its Strategic Implications for the United States; Tocqueveille War.

  4. Compartmental Targeting for mTHPC-Based Photodynamic Treatment In Vivo: Correlation of Efficiency, Pharmacokinetics, and Regional Distribution of Apoptosis

    SciTech Connect

    Garrier, Julie; Bressenot, Aude; Graefe, Susanna

    2010-10-01

    Purpose: The present study investigates the efficacy of compartmental targeting in xenografted tumors treated by meta-tetra(hydroxyphenyl)chlorin (mTHPC)-mediated photodynamic therapy (PDT). The therapeutic efficacy was, furthermore, related to a regional photoinduced distribution of apoptosis and an mTHPC biodistribution profile. Methods and Materials: Mice bearing EMT6 tumors were subjected to a single irradiation (10 J/cm{sup 2}) of red laser light (652 nm) at different intervals after a single- (0.3 mg/kg or 0.15 mg/kg) or double-intravenous (2 x 0.15 mg/kg) injection(s) of mTHPC. Efficiency of the treatment was evaluated by monitoring tumor regrowth. mTHPC pharmacokinetics were assessed by high-performance liquid chromatography analysis of excised organs. The regional distribution of apoptosis in tumor sections was investigated with a newly developed colabelling immunohistochemistry technique. Results: A fractionated double-injection protocol of mTHPC with 24-h and 3-h drug-light intervals (DLI) yielded 100% tumor cure, with tumors presenting a massive apoptosis of neoplastic cells along with a distortion of vessels. The best efficiency for a single injection (0.3 mg/kg) was about 54% tumor cure and corresponded to a DLI of 3 h. At this DLI, tumors showed apoptosis of endothelial cells in residual vessels. Concentrations of mTHPC observed in plasma and tumor for the fractionated injection were not statistically different and were less than the total drug dose in each compartment. Conclusions: The present work suggests that clinical PDT protocols with mTHPC could be greatly improved by fractionation of the drug administration. Time points should be chosen based on the intratumoral spatiotemporal drug distribution.

  5. Elevated compartmentalization of Na+ into vacuoles improves salt and cold stress tolerance in sweet potato (Ipomoea batatas).

    PubMed

    Fan, Weijuan; Deng, Gaifang; Wang, Hongxia; Zhang, Hongxia; Zhang, Peng

    2015-08-01

    Salinity and low temperature are the main limiting factors for sweet potato (Ipomoea batatas) growth and agricultural productivity. Various studies have shown that plant NHX-type antiporter plays a crucial role in regulating plant tolerance to salt stress by intracellular Na(+) compartmentalization. The Arabidopsis thaliana AtNHX1 gene that encodes a vacuolar Na(+) /H(+) antiporter was introduced into the sweet potato cultivar Xushu-22 by Agrobacterium-mediated transformation to confer abiotic stress tolerance. Stable insertion of AtNHX1 into the sweet potato genome and its expression was confirmed by Southern blot and reverse transcription-polymerase chain reaction (RT-PCR). A remarkably higher Na(+) /H(+) exchange activity of tonoplast membrane from transgenic sweet potato lines (NOE) in comparison with wild-type (WT) plants confirmed the vacuolar antiporter function in mediating Na(+) /H(+) exchange. Under salt stress, NOE plants accumulated higher Na(+) and K(+) levels in their tissues compared with WT plants, maintaining high K(+) /Na(+) ratios. Consequently, NOE plants showed enhanced protection against cell damage due to the increased proline accumulation, preserved cell membrane integrity, enhanced reactive oxygen species (ROS) scavenging (e.g. increased superoxide dismutase activity), and reduced H2 O2 and malondialdehyde (MDA) production. Moreover, the transgenic plants showed improved cold tolerance through multiple mechanisms of action, revealing the first molecular evidence for NHX1 function in cold response. The transgenic plants showed better biomass production and root yield under stressful conditions. These findings demonstrate that overexpressing AtNHX1 in sweet potato renders the crop tolerant to both salt and cold stresses, providing a greater capacity for the use of AtNHX1 in improving crop performance under combined abiotic stress conditions.

  6. Ferrocene-based compartmental ligand for the assembly of neutral Zn(II)/Ln(III) heterometallic complexes.

    PubMed

    Chandrasekhar, Vadapalli; Chakraborty, Amit; Sañudo, E Carolina

    2013-10-01

    A ferrocene-based compartmental ligand, H2L, was synthesized by the reaction of diacetyl ferrocene with hydrazine hydrate followed by a condensation reaction with o-vanillin. [L](2-) possesses a dual coordination pocket, an inner pocket of 2 imino nitrogens and two phenolate oxygens and an outer pocket of two phenolate and two methoxy oxygen atoms. Utilizing this ligand, several Zn(II)/Ln(III) heterobimetallic complexes were assembled: [LZn(μ-OAc)Dy(NO3)2] (2), [LZn(μ-OAc)Tb(NO3)2] (3), [LZn(μ-OAc)Gd(NO3)2·2CHCl3] (4), [LZn(μ-OAc)Er(NO3)2] (5), [LZn(μ-OAc)Ho(NO3)2] (6), [LZn(μ-OAc)Eu(NO3)2] (7). All of these metal complexes are neutral and isostructural: the Zn(II) ion occupies the inner coordination pocket while the Ln(III) ion occupies the outer coordination pocket of the doubly deprotonated ligand [L](2-). Zn(II) has a coordination number of 5 (2N, 3O) in a square pyramidal coordination geometry while Ln(III) has a coordination number of 9 (9O) in a distorted tricapped trigonal prismatic geometry. Zn(II) and the 4f metal ion are bridged to each other by two phenolate oxygen atoms and an acetate ligand. ESI-MS reveals that 2-7 retain their structural integrity in solution. Cyclic voltammetry of 1-7 revealed a quasi-reversible oxidation (involving the ferrocene motif) and an irreversible reduction of the hydrazone unit. Magnetic studies of 2, 3 and 6 were carried out. Ac susceptibility studies did not reveal slow relaxation of magnetization.

  7. Compartmentalized self-replication (CSR) selection of Thermococcus litoralis Sh1B DNA polymerase for diminished uracil binding.

    PubMed

    Tubeleviciute, Agne; Skirgaila, Remigijus

    2010-08-01

    The thermostable archaeal DNA polymerase Sh1B from Thermococcus litoralis has a typical uracil-binding pocket, which in nature plays an essential role in preventing the accumulation of mutations caused by cytosine deamination to uracil and subsequent G-C base pair transition to A-T during the genomic DNA replication. The uracil-binding pocket recognizes and binds uracil base in a template strand trapping the polymerase. Since DNA replication stops, the repair systems have a chance to correct the promutagenic event. Archaeal family B DNA polymerases are employed in various PCR applications. Contrary to nature, in PCR the uracil-binding property of archaeal polymerases is disadvantageous and results in decreased DNA amplification yields and lowered sensitivity. Furthermore, in diagnostics qPCR, RT-qPCR and end-point PCR are performed using dNTP mixtures, where dTTP is partially or fully replaced by dUTP. Uracil-DNA glycosylase treatment and subsequent heating of the samples is used to degrade the DNA containing uracil and prevent carryover contamination, which is the main concern in diagnostic laboratories. A thermostable archaeal DNA polymerase with the abolished uracil binding would be a highly desirable and commercially interesting product. An attempt to disable uracil binding in DNA polymerase Sh1B from T. litoralis by generating site-specific mutants did not yield satisfactory results. However, a combination of random mutagenesis of the whole polymerase gene and compartmentalized self-replication was successfully used to select variants of thermostable Sh1B polymerase capable of performing PCR with dUTP instead of dTTP.

  8. An extension to the compartmental model of type 1 diabetic patients to reproduce exercise periods with glycogen depletion and replenishment.

    PubMed

    Hernández-Ordoñez, M; Campos-Delgado, D U

    2008-01-01

    The purpose of this work is to present the main interactions promoted by exercise and synthesize them into mathematical equations. It is intended to extend the ability of the compartmental glucose-insulin model introduced by Sorensen [1985. A physiologic model of glucose metabolism in man and its use to design and assess improved insulin therapies for diabetes. Ph.D. Dissertation, Chemical Engineering Department, MIT, Cambridge] to reproduce variations in the blood glucose concentration induced by exercise in diabetic patients and to complement the previous work by Lenart and Parker [2002. Modeling exercise effects in type I diabetic patients. In: Proceedings of the 15th Triennial World Congress, Barcelona, Spain] and Lenart, DiMascio and Parker [2002. Modeling glycogen-exercise interactions in type I diabetic patients. In: Proceedings of the A.I.Ch.E. Annual Meeting, Indianapolis, IN]. The immediate consequences of exercise are incorporated in this research: redistribution of blood flows, increments in peripheral glucose and insulin uptakes, and increment in hepatic glucose production. The extended model was verified with experimental data for light and moderate intensity exercise. In addition, data extrapolation was introduced to simulate heavy intensity exercise. The hepatic glycogen reservoir limits the peripheral glucose uptake for prolonged exercise. Therefore, the depletion and replenishment of hepatic glycogen were modeled, looking to reproduce the blood glucose levels for a type 1 diabetic patient during a normal day, with meal intakes, insulin infusions and/or boluses, and a predefined exercise regime. From the extensive simulation evaluation, it is found that the new exercise model provides a good approximation to the available experimental data from literature.

  9. Compartmental modeling of and radiation dose estimates for {sup 186}Re NR-LU-10 monoclonal antibody

    SciTech Connect

    Stubbs, J.B.; Beaumier, P.L.; Breitz, H.B.

    1994-05-01

    A clinical data set developed using {sup 186}Re labeled NR-LU-10, a pancarcinoma monoclonal antibody utilized for radioimmunotherapy, has been reanalyzed by compartmental modeling techniques. The pharmacokinetics and dosimetry estimates, derived from standard exponential curve filling, have been reported previously. In this work, we describe an 18-compartment model that integrates all measured biological data into a comprehensive biokinetic model. The model was developed with the SAAM (Simulation Analysis and Modeling) software. Residence times were calculated by integrating model-predicted time activity curves in tumor and 10 organs or tissues. Activity excreted via the hepatobiliary route was assumed to follow the ICRP 30 GI tract model, and a dynamic urinary bladder model (void interval = 4.8 hr) was used to simulate excretion via the urinary pathway. Dose estimates for 24 organs were calculated using the MIRD formalism. Tumor doses were estimated using absorbed fractions for electron sources uniformly distributed in small spheres. The model predicts that most activity is excreted (70% urine, 27% feces) by 300 hours post injection with the highest absorbed dose received by the excretory organs: lower large intestine (2.6 mGy/MBq), kidneys (1.4 mGy/MBq), upper large intestine (1.1 mGy/MBq). Tumor doses ranged from 180-1.8 mGy/MBq, depending on size (assuming tumor masses ranging from 1-100 grams). This multicompartmental model is comprehensive, provides conservation of activity, enables the modeling of hypothetical conditions (e.g., effect of plasma immunopheresis), and permits insight into the biological system.

  10. Morphological features, distribution and compartmental organization of the nicotinamide adenine dinucleotide phosphate reduced-diaphorase interneurons in the human striatum.

    PubMed

    Bernácer, Javier; Prensa, Lucía; Giménez-Amaya, José Manuel

    2005-08-29

    Striatal nicotinamide adenine dinucleotide phosphate reduced-diaphorase (NADPH-d)-positive (+) cells are one of the major classes of striatal interneurons. The present study analyzes their somatodendritic morphology, distribution pattern, and compartmental organization in the caudate nucleus (CN) and putamen (Put) of nine normal human brains. The following striatal territories are examined: 1) the precommissural head of the CN; 2) the postcommissural head of the CN; 3) the body of the CN; 4) the gyrus of the CN; 5) the tail of the CN; 6) the precommissural Put; and 7) the postcommissural Put. Three morphologically distinct types of NADPH-d+ neurons were found in each of these territories. The two most common NADPH-d+ neurons displayed an ovoid or triangular perikaryon from which several thick primary dendrites emerged, although much less numerous, bipolar-shaped NADPH-d+ cells were also observed. The highest density of NADPH-d+ neurons was found in the gyrus of the CN, followed by the body of the CN, tail of the CN, postcommissural head of the CN, postcommissural Put, precommissural head of the CN, and precommissural Put. The matrix was the striatal compartment with the densest NADPH-d+ neuronal population. Some of these cells also occurred in the center and peripheral regions of the striosomes located in the head of the CN and in the Put. In the body and gyrus of the CN, the striosomes were largely devoid of these striatal interneurons. Knowledge of the density and distribution of these interneurons should advance our understanding of the organization of the normal human striatum and help to evaluate the effects of neurodegenerative processes on cell density.

  11. Quantification of microvascular cerebral blood flux and late-stage tumor compartmentalization in 9L gliosarcoma using flow enhanced MRI.

    PubMed

    Reynaud, Olivier; Geffroy, Françoise; Ciobanu, Luisa

    2013-06-01

    Measurements of tumor microvasculature are important to obtain an understanding of tumor angiogenesis and for the evaluation of therapies. In this work, we characterize the evolution of the microvascular flux at different stages of tumor growth in the 9L rat brain tumor model. The absolute quantification of cerebral blood flux is achieved with MRI at 7 T using the flow enhanced signal intensity (FENSI) method. FENSI flux maps were obtained between 5 and 14 days after glioma cell inoculation. Based on cerebral blood flux maps, we highlighted two main stages of tumor growth, below and above 3 mm, presenting distinct flux patterns and vascular properties. No significant difference emerged from the group analysis performed on the data collected at an early developmental stage (tumor size < 3 mm) when compared with healthy tissue. At a late developmental stage (tumor size > 3 mm), we observed a significant decrease in the cerebral blood flux inside the gliosarcoma (-33%, p < 0.01) and compartmentalization of the tumor (p < 0.05). FENSI flux maps delineated a low-flux tumor core (58 ± 17 μL/min/cm(2) ) and higher vascularized regions around the tumor periphery (85 ± 21 μL/min/cm(2) ). Histology was performed on 11 animals to finely probe the intratumor heterogeneity and microvessel density, and the results were compared with the information derived from FENSI flux maps. The hyper- and hypoperfused tumor regions revealed with FENSI at the late tumor developmental stage correlated well with the ratios of high and low blood vessel density (R(2) = 0.41) and fractional vascular surface (R(2) = 0.67) observed with fluorescence microscopy [cluster of differentiation 31 (CD31) staining].

  12. The role of extracellular conductivity profiles in compartmental models for neurons: particulars for layer 5 pyramidal cells.

    PubMed

    Wang, Kai; Riera, Jorge; Enjieu-Kadji, Herve; Kawashima, Ryuta

    2013-07-01

    With the rapid increase in the number of technologies aimed at observing electric activity inside the brain, scientists have felt the urge to create proper links between intracellular- and extracellular-based experimental approaches. Biophysical models at both physical scales have been formalized under assumptions that impede the creation of such links. In this work, we address this issue by proposing a multicompartment model that allows the introduction of complex extracellular and intracellular resistivity profiles. This model accounts for the geometrical and electrotonic properties of any type of neuron through the combination of four devices: the integrator, the propagator, the 3D connector, and the collector. In particular, we applied this framework to model the tufted pyramidal cells of layer 5 (PCL5) in the neocortex. Our model was able to reproduce the decay and delay curves of backpropagating action potentials (APs) in this type of cell with better agreement with experimental data. We used the voltage drops of the extracellular resistances at each compartment to approximate the local field potentials generated by a PCL5 located in close proximity to linear microelectrode arrays. Based on the voltage drops produced by backpropagating APs, we were able to estimate the current multipolar moments generated by a PCL5. By adding external current sources in parallel to the extracellular resistances, we were able to create a sensitivity profile of PCL5 to electric current injections from nearby microelectrodes. In our model for PCL5, the kinetics and spatial profile of each ionic current were determined based on a literature survey, and the geometrical properties of these cells were evaluated experimentally. We concluded that the inclusion of the extracellular space in the compartmental models of neurons as an extra electrotonic medium is crucial for the accurate simulation of both the propagation of the electric potentials along the neuronal dendrites and the

  13. The role of extracellular conductivity profiles in compartmental models for neurons: particulars for layer 5 pyramidal cells.

    PubMed

    Wang, Kai; Riera, Jorge; Enjieu-Kadji, Herve; Kawashima, Ryuta

    2013-07-01

    With the rapid increase in the number of technologies aimed at observing electric activity inside the brain, scientists have felt the urge to create proper links between intracellular- and extracellular-based experimental approaches. Biophysical models at both physical scales have been formalized under assumptions that impede the creation of such links. In this work, we address this issue by proposing a multicompartment model that allows the introduction of complex extracellular and intracellular resistivity profiles. This model accounts for the geometrical and electrotonic properties of any type of neuron through the combination of four devices: the integrator, the propagator, the 3D connector, and the collector. In particular, we applied this framework to model the tufted pyramidal cells of layer 5 (PCL5) in the neocortex. Our model was able to reproduce the decay and delay curves of backpropagating action potentials (APs) in this type of cell with better agreement with experimental data. We used the voltage drops of the extracellular resistances at each compartment to approximate the local field potentials generated by a PCL5 located in close proximity to linear microelectrode arrays. Based on the voltage drops produced by backpropagating APs, we were able to estimate the current multipolar moments generated by a PCL5. By adding external current sources in parallel to the extracellular resistances, we were able to create a sensitivity profile of PCL5 to electric current injections from nearby microelectrodes. In our model for PCL5, the kinetics and spatial profile of each ionic current were determined based on a literature survey, and the geometrical properties of these cells were evaluated experimentally. We concluded that the inclusion of the extracellular space in the compartmental models of neurons as an extra electrotonic medium is crucial for the accurate simulation of both the propagation of the electric potentials along the neuronal dendrites and the

  14. Components and regulation of nuclear transport processes.

    PubMed

    Cautain, Bastien; Hill, Richard; de Pedro, Nuria; Link, Wolfgang

    2015-02-01

    The spatial separation of DNA replication and gene transcription in the nucleus and protein translation in the cytoplasm is a uniform principle of eukaryotic cells. This compartmentalization imposes a requirement for a transport network of macromolecules to shuttle these components in and out of the nucleus. This nucleo-cytoplasmic transport of macromolecules is critical for both cell physiology and pathology. Consequently, investigating its regulation and disease-associated alterations can reveal novel therapeutic approaches to fight human diseases, such as cancer or viral infection. The characterization of the nuclear pore complex, the identification of transport signals and transport receptors, as well as the characterization of the Ran system (providing the energy source for efficient cargo transport) has greatly facilitated our understanding of the components, mechanisms and regulation of the nucleo-cytoplasmic transport of proteins in our cells. Here we review this knowledge with a specific emphasis on the selection of disease-relevant molecular targets for potential therapeutic intervention.

  15. Nuclear ventriculography

    MedlinePlus

    ... ventriculography (RNV); Multiple gate acquisition scan (MUGA); Nuclear cardiology; Cardiomyopathy - nuclear ventriculography ... 56. Udelson JE, Dilsizian V, Bonow RO. Nuclear cardiology. In: Bonow RO, Mann DL, Zipes DP, Libby ...

  16. Nuclear Medicine.

    ERIC Educational Resources Information Center

    Badawi, Ramsey D.

    2001-01-01

    Describes the use of nuclear medicine techniques in diagnosis and therapy. Describes instrumentation in diagnostic nuclear medicine and predicts future trends in nuclear medicine imaging technology. (Author/MM)

  17. Subcellular compartmentalization of Cd and Zn in two bivalves. I. Significance of metal-sensitive fractions (MSF) and biologically detoxified metal (BDM)

    USGS Publications Warehouse

    Wallace, W.G.; Lee, B.-G.; Luoma, S.N.

    2003-01-01

    Many aspects of metal accumulation in aquatic invertebrates (i.e. toxicity, tolerance and trophic transfer) can be understood by examining the subcellular partitioning of accumulated metal. In this paper, we use a compartmentalization approach to interpret the significance of metal, species and size dependence in the subcellular partitioning of Cd and Zn in the bivalves Macoma balthica and Potamocorbula amurensis. Of special interest is the compartmentalization of metal as metal-sensitive fractions (MSF) (i.e. organelles and heat-sensitive proteins, termed 'enzymes' hereafter) and biologically detoxified metal (BDM) (i.e. metallothioneins [MT] and metal-rich granules [MRG]). Clams from San Francisco Bay, CA, were exposed for 14 d to seawater (20??? salinity) containing 3.5 ??g l-1 Cd and 20.5 ??g l-1 Zn, including 109Cd and 65Zn as radiotracers. Uptake was followed by 21 d of depuration. The subcellular partitioning of metal within clams was examined following exposure and loss. P. amurensis accumulated ???22x more Cd and ???2x more Zn than M. balthica. MT played an important role in the storage of Cd in P. amurensis, while organelles were the major site of Zn accumulation. In M. balthica, Cd and Zn partitioned similarly, although the pathway of detoxification was metal-specific (MRG for Cd; MRG and MT for Zn). Upon loss, M. balthica depurated ???40% of Cd with Zn being retained; P. amurensis retained Cd and depurated Zn (???40%). During efflux, Cd and Zn concentrations in the MSF compartment of both clams declined with metal either being lost from the animal or being transferred to the BDM compartment. Subcellular compartmentalization was also size-dependent, with the importance of BDM increasing with clam size; MSF decreased accordingly. We hypothesized that progressive retention of metal as BDM (i.e. MRG) with age may lead to size dependency of metal concentrations often observed in some populations of M. balthica.

  18. Compartmentalized replication of R5 T cell-tropic HIV-1 in the central nervous system early in the course of infection.

    PubMed

    Sturdevant, Christa Buckheit; Joseph, Sarah B; Schnell, Gretja; Price, Richard W; Swanstrom, Ronald; Spudich, Serena

    2015-03-01

    Compartmentalized HIV-1 replication within the central nervous system (CNS) likely provides a foundation for neurocognitive impairment and a potentially important tissue reservoir. The timing of emergence and character of this local CNS replication has not been defined in a population of subjects. We examined the frequency of elevated cerebrospinal fluid (CSF) HIV-1 RNA concentration, the nature of CSF viral populations compared to the blood, and the presence of a cellular inflammatory response (with the potential to bring infected cells into the CNS) using paired CSF and blood samples obtained over the first two years of infection from 72 ART-naïve subjects. Using single genome amplification (SGA) and phylodynamics analysis of full-length env sequences, we compared CSF and blood viral populations in 33 of the 72 subjects. Independent HIV-1 replication in the CNS (compartmentalization) was detected in 20% of sample pairs analyzed by SGA, or 7% of all sample pairs, and was exclusively observed after four months of infection. In subjects with longitudinal sampling, 30% showed evidence of CNS viral replication or pleocytosis/inflammation in at least one time point, and in approximately 16% of subjects we observed evolving CSF/CNS compartmentalized viral replication and/or a marked CSF inflammatory response at multiple time points suggesting an ongoing or recurrent impact of the infection in the CNS. Two subjects had one of two transmitted lineages (or their recombinant) largely sequestered within the CNS shortly after transmission, indicating an additional mechanism for establishing early CNS replication. Transmitted variants were R5 T cell-tropic. Overall, examination of the relationships between CSF viral populations, blood and CSF HIV-1 RNA concentrations, and inflammatory responses suggested four distinct states of viral population dynamics, with associated mechanisms of local viral replication and the early influx of virus into the CNS. This study considerably

  19. Microfluidic Compartmentalized Directed Evolution

    PubMed Central

    Paegel, Brian M.; Joyce, Gerald F.

    2010-01-01

    Summary Directed evolution studies often make use of water-in-oil compartments, which conventionally are prepared by bulk emulsification, a crude process that generates non-uniform droplets and can damage biochemical reagents. A microfluidic emulsification circuit was devised that generates uniform water-in-oil droplets (21.9 ± 0.8 μm radius) with high throughput (107–108 droplets per hour). The circuit contains a radial array of aqueous flow nozzles that intersect a surrounding oil flow channel. This device was used to evolve RNA enzymes with RNA ligase activity, selecting enzymes that could resist inhibition by neomycin. Each molecule in the population had the opportunity to undergo 108-fold selective amplification within its respective compartment. Then the progeny RNAs were harvested and used to seed new compartments. During five rounds of this procedure, the enzymes acquired mutations that conferred resistance to neomycin and caused some enzymes to become dependent on neomycin for optimal activity. PMID:20659684

  20. Double-input compartmental modeling and spectral analysis for the quantification of positron emission tomography data in oncology

    NASA Astrophysics Data System (ADS)

    Tomasi, G.; Kimberley, S.; Rosso, L.; Aboagye, E.; Turkheimer, F.

    2012-04-01

    In positron emission tomography (PET) studies involving organs different from the brain, ignoring the metabolite contribution to the tissue time-activity curves (TAC), as in the standard single-input (SI) models, may compromise the accuracy of the estimated parameters. We employed here double-input (DI) compartmental modeling (CM), previously used for [11C]thymidine, and a novel DI spectral analysis (SA) approach on the tracers 5-[18F]fluorouracil (5-[18F]FU) and [18F]fluorothymidine ([18F]FLT). CM and SA were performed initially with a SI approach using the parent plasma TAC as an input function. These methods were then employed using a DI approach with the metabolite plasma TAC as an additional input function. Regions of interest (ROIs) corresponding to healthy liver, kidneys and liver metastases for 5-[18F]FU and to tumor, vertebra and liver for [18F]FLT were analyzed. For 5-[18F]FU, the improvement of the fit quality with the DI approaches was remarkable; in CM, the Akaike information criterion (AIC) always selected the DI over the SI model. Volume of distribution estimates obtained with DI CM and DI SA were in excellent agreement, for both parent 5-[18F]FU (R2 = 0.91) and metabolite [18F]FBAL (R2 = 0.99). For [18F]FLT, the DI methods provided notable improvements but less substantial than for 5-[18F]FU due to the lower rate of metabolism of [18F]FLT. On the basis of the AIC values, agreement between [18F]FLT Ki estimated with the SI and DI models was good (R2 = 0.75) for the ROIs where the metabolite contribution was negligible, indicating that the additional input did not bias the parent tracer only-related estimates. When the AIC suggested a substantial contribution of the metabolite [18F]FLT-glucuronide, on the other hand, the change in the parent tracer only-related parameters was significant (R2 = 0.33 for Ki). Our results indicated that improvements of DI over SI approaches can range from moderate to substantial and are more significant for tracers with

  1. Syntectonic fluid flow and fluid compartmentalization in a compressive basin: Example of the Jaca basin (Southwest Pyrenees, Spain)

    NASA Astrophysics Data System (ADS)

    Lacroix, Brice; Travé, Anna; Buatier, Martine; Labaume, Pierre

    2013-04-01

    During compressive events, deformation in sedimentary basins is mainly accommodated by thrust faults emplacement and related fold growth. In such a structure, thrust faults are generally rooted in the basement and may act as conduits or barriers for crustal fluid flow. However, most of recent studies suggest that fluid flow through such discontinuities is not so evident and depends on the structural levels of the thrust inside the fold-and-thrust belt. In order to constrain the paleofluid flow through the Jaca thrust-sheet-top basin (Paleogene southwest-Pyrenean fold-and-thrust belt) we focus our study on different thrust faults located at different structural levels. The microstructures observed in the different studied fault zones are similar and consist of pervasive cleavage, calcite shear and extension veins and late dilatation veins. In order to constrain the nature and the source of fluids involved in fluid-rock interactions in fault zones, a geochemical approach, based on oxygen and carbon stable isotopes and trace elements on calcite, was adopted on the different vein generations and host rocks. The results suggest a high complexity in the paleo-hydrological behaviors of thrust faults evidencing a fluid-flow compartmentalization of the basin. North of the Jaca basin, previous studies in the southern part of the Axial Zones showed the contribution of deep metamorphic water, probably derived from the Paleozoic basement, along along fault zones related the major Gavarnie thrust. Contrarily, in the northern part of the Jaca basin, we evidence the contribution of formation water during the Monte Perdido thrust fault activity. These data suggest a closed hydrological fluid system where distance of fluid flow did not exceeded 70 m. On the other hand, the Jaca and Cotiella thrust faults, both located more to the south in the basin, are characterized by a composite fluid flow system. Indeed, stable isotopes and trace elements compositions of the first generation of

  2. Regulation of protease-activated receptor (PAR) 1 and PAR4 signaling in human platelets by compartmentalized cyclic nucleotide actions.

    PubMed

    Bilodeau, Matthew L; Hamm, Heidi E

    2007-08-01

    Thrombin potently regulates human platelets by the G protein-coupled receptors protease-activated receptor (PAR) 1 and PAR4. Platelet activation by thrombin and other agonists is broadly inhibited by prostacyclin and nitric oxide acting through adenylyl and guanylyl cyclases to elevate cAMP and cGMP levels, respectively. Using forskolin and YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole] to selectively activate the adenylyl and guanylyl cyclases, respectively, and the membrane-permeable analogs N(6),2'-O-dibutyryladenosine-3'-5'-cAMP (dibutyryl-cAMP) and 8-(4-parachlorophenylthoi)-cGMP (8-pCPT-cGMP), we sought to identify key antiplatelet steps for cyclic nucleotide actions in blocking platelet activation by PAR1 versus PAR4. Platelet aggregation by PAR1 or PAR4 was inhibited with similar EC(50) of 1.2 to 2.1 microM forskolin, 31 to 33 microM YC-1, 57 to 150 microM dibutyryl-cAMP, and 220 to 410 microM 8-pCPT-cGMP. There was a marked left shift in the inhibitory potencies of forskolin and YC-1 for alpha-granule release and glycoprotein IIbIIIa/integrin alphaIIbbeta3 activation (i.e., EC(50) of 1-60 and 40-1300 nM, respectively) that was not observed for dibutyryl-cAMP and 8-pCPT-cGMP (i.e., EC(50) of 200-600 and 40-140 microM, respectively). This inhibition was essentially instantaneous, and measurements of cyclic nucleotide levels and kinase activities support a model of compartmentation involving the cyclic nucleotide effectors and regulators and the key molecular targets for this platelet inhibition. The different sensitivities of PAR1 and PAR4 to inhibition of calcium mobilization and dense granule release identify key antiplatelet steps for cyclic nucleotide actions and are consistent with the signaling models for these receptors. Specifically, PAR4 inhibition depends on the regulation of both calcium mobilization and dense granule release, and PAR1 inhibition depends predominantly on the regulation of dense granule release. PMID:17525299

  3. Nuclear weapons and nuclear war

    SciTech Connect

    Cassel, C.; McCally, M.; Abraham, H.

    1984-01-01

    This book examines the potential radiation hazards and environmental impacts of nuclear weapons. Topics considered include medical responsibility and thermonuclear war, the threat of nuclear war, nuclear weaponry, biological effects, radiation injury, decontamination, long-term effects, ecological effects, psychological aspects, the economic implications of nuclear weapons and war, ethics, civil defense, arms control, nuclear winter, and long-term biological consequences of nuclear war.

  4. Nuclear Theory - Nuclear Power

    NASA Astrophysics Data System (ADS)

    Svenne, J. P.; Canton, L.; Kozier, K. S.

    2008-01-01

    The results from modern nuclear theory are accurate and reliable enough to be used for practical applications, in particular for scattering that involves few-nucleon systems of importance to nuclear power. Using well-established nucleon-nucleon (NN) interactions that fit well the NN scattering data, and the AGS form of the three-body theory, we have performed precise calculations of low-energy neutron-deuteron (n+d) scattering. We show that three-nucleon force effects that have impact on the low-energy vector analyzing powers have no practical effects on the angular distribution of the n+d cross-section. There appear to be problems for this scattering in the evaluated nuclear data file (ENDF) libraries, at the incident neutron energies less than 3.2 MeV. Supporting experimental data in this energy region are rather old (>25 years), sparse and often inconsistent. Our three-body results at low energies, 50 keV to 10.0 MeV, are compared to the ENDF/B-VII.0 and JENDL (Japanese Evaluated Nuclear Data Library) -3.3 evaluated angular distributions. The impact of these results on the calculated reactivity for various critical systems involving heavy water is shown.

  5. Nuclear choices

    SciTech Connect

    Wolfson, R.

    1991-01-01

    This book contains part of the series New Liberal Arts, which is intended to make science and technology more accessible to students of the liberal arts. Volume in hand provides a comprehensive, multifaceted examination of nuclear energy, in nontechnical terms. Wolfson explains the basics of nuclear energy and radiation, nuclear power..., and nuclear weapons..., and he invites readers to make their own judgments on controversial nuclear issues. Illustrated with photos and diagrams. Each chapter contains suggestions for additional reading and a glossary. For policy, science, and general collections in all libraries. (ES) Topics contained include Atoms and nuclei. Effects and uses of radiation. Energy and People. Reactor safety. Nuclear strategy. Defense in the nuclear age. Nuclear power, nuclear weapons, and nuclear futures.

  6. Assessing the Metabolic Impact of Nitrogen Availability Using a Compartmentalized Maize Leaf Genome-Scale Model1[C][W][OPEN

    PubMed Central

    Simons, Margaret; Saha, Rajib; Amiour, Nardjis; Kumar, Akhil; Guillard, Lenaïg; Clément, Gilles; Miquel, Martine; Li, Zhenni; Mouille, Gregory; Lea, Peter J.; Hirel, Bertrand; Maranas, Costas D.

    2014-01-01

    Maize (Zea mays) is an important C4 plant due to its widespread use as a cereal and energy crop. A second-generation genome-scale metabolic model for the maize leaf was created to capture C4 carbon fixation and investigate nitrogen (N) assimilation by modeling the interactions between the bundle sheath and mesophyll cells. The model contains gene-protein-reaction relationships, elemental and charge-balanced reactions, and incorporates experimental evidence pertaining to the biomass composition, compartmentalization, and flux constraints. Condition-specific biomass descriptions were introduced that account for amino acids, fatty acids, soluble sugars, proteins, chlorophyll, lignocellulose, and nucleic acids as experimentally measured biomass constituents. Compartmentalization of the model is based on proteomic/transcriptomic data and literature evidence. With the incorporation of information from the MetaCrop and MaizeCyc databases, this updated model spans 5,824 genes, 8,525 reactions, and 9,153 metabolites, an increase of approximately 4 times the size of the earlier iRS1563 model. Transcriptomic and proteomic data have also been used to introduce regulatory constraints in the model to simulate an N-limited condition and mutants deficient in glutamine synthetase, gln1-3 and gln1-4. Model-predicted results achieved 90% accuracy when comparing the wild type grown under an N-complete condition with the wild type grown under an N-deficient condition. PMID:25248718

  7. Compartmentation of the cerebellar cortex of hummingbirds (Aves: Trochilidae) revealed by the expression of zebrin II and phospholipase C beta 4.

    PubMed

    Iwaniuk, Andrew N; Marzban, Hassan; Pakan, Janelle M P; Watanabe, Masahiko; Hawkes, Richard; Wylie, Douglas R W

    2009-01-01

    The parasagittal organization of the mammalian cerebellar cortex into zones has been well characterized by immunohistochemical, hodological and physiological studies in recent years. The pattern of these parasagittal bands across the cerebellum is highly conserved across mammals, but whether a similar conservation of immunohistochemically defined parasagittal bands occurs within birds has remained uncertain. Here, we examine the compartmentation of the cerebellar cortex of a group of birds with unique cerebellar morphology-hummingbirds (Trochilidae). Immunohistochemical techniques were used to characterize the expression of zebrin II (aldolase C) and phospholipase C beta 4 (PLC beta 4) in the cerebellar cortex of two hummingbird species. A series of zebrin II immunopositive/immunonegative parasagittal stripes was apparent across most folia representing three major transverse zones: an anterior zone with a central stripe flanked by three lateral stripes on either side; a central zone of high/low immunopositive stripes; and a posterior zone with a central stripe flanked by four to six lateral stripes on either side. In addition, both folia I and X were uniformly immunopositive. The pattern of PLC beta 4 immunoreactivity was largely complementary-PLC beta 4 positive stripes were zebrin II negative and vice versa. The similarity of zebrin II expression between the hummingbirds and the pigeon indicates that the neurochemical compartmentation of the cerebellar cortex in birds is highly conserved, but species differences in the number and width of stripes do occur.

  8. Mechanisms of salt tolerance in habanero pepper plants (Capsicum chinense Jacq.): Proline accumulation, ions dynamics and sodium root-shoot partition and compartmentation

    PubMed Central

    Bojórquez-Quintal, Emanuel; Velarde-Buendía, Ana; Ku-González, Ángela; Carillo-Pech, Mildred; Ortega-Camacho, Daniela; Echevarría-Machado, Ileana; Pottosin, Igor; Martínez-Estévez, Manuel

    2014-01-01

    Despite its economic relevance, little is known about salt tolerance mechanisms in pepper plants. To address this question, we compared differences in responses to NaCl in two Capsicum chinense varieties: Rex (tolerant) and Chichen-Itza (sensitive). Under salt stress (150 mM NaCl over 7 days) roots of Rex variety accumulated 50 times more compatible solutes such as proline compared to Chichen-Itza. Mineral analysis indicated that Na+ is restricted to roots by preventing its transport to leaves. Fluorescence analysis suggested an efficient Na+ compartmentalization in vacuole-like structures and in small intracellular compartments in roots of Rex variety. At the same time, Na+ in Chichen-Itza plants was compartmentalized in the apoplast, suggesting substantial Na+ extrusion. Rex variety was found to retain more K+ in its roots under salt stress according to a mineral analysis and microelectrode ion flux estimation (MIFE). Vanadate-sensitive H+ efflux was higher in Chichen-Itza variety plants, suggesting a higher activity of the plasma membrane H+-ATPase, which fuels the extrusion of Na+, and, possibly, also the re-uptake of K+. Our results suggest a combination of stress tolerance mechanisms, in order to alleviate the salt-induced injury. Furthermore, Na+ extrusion to apoplast does not appear to be an efficient strategy for salt tolerance in pepper plants. PMID:25429292

  9. Inhibition of Glutathione Biosynthesis Alters Compartmental Redox Status and the Thiol Proteome in Organogenesis-Stage Rat Conceptuses

    PubMed Central

    Harris, Craig; Shuster, Daniel Z.; Gomez, Rosaicela Roman; Sant, Karilyn E.; Reed, Matthew S.; Pohl, Jan; Hansen, Jason M.

    2013-01-01

    significant net oxidation was seen in the BSO-treated AF compartment after 6 hr. Biotinylated iodoacetamide (BIAM) labeling of proteins revealed the significant thiol-oxidation of many EMB proteins following BSO treatment. Quantitative changes in the thiol proteome, associated with developmentally-relevant pathways, were detected using isotope coded affinity tag (ICAT) labeling and mass spectroscopy. Adaptive pathways were selectively enriched with increased concentrations of proteins involved in mRNA processing (splicesome) and mRNA stabilization (glycolysis, GAPDH), as well as, protein synthesis (aminoacyl-tRNA) and protein folding (antigen processing, Hsp70, protein disulfide isomerase). These results show the ability of chemical and environmental modulators to selectively alter compartmental intracellular and extracellular GSH and Cys concentrations and change their corresponding Eh within the intact viable conceptus. The altered Eh were also of sufficient magnitude to alter the redox proteome and change relative protein concentrations suggesting that the mechanistic links through which environmental factors inform and regulate developmental signaling pathways may be discovered using systems developmental biology techniques. PMID:23736079

  10. Nuclear Winter.

    ERIC Educational Resources Information Center

    Ehrlich, Anne

    1984-01-01

    "Nuclear Winter" was recently coined to describe the climatic and biological effects of a nuclear war. These effects are discussed based on models, simulations, scenarios, and projections. Effects on human populations are also considered. (JN)

  11. Nuclear Chemistry.

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1979

    1979-01-01

    Provides a brief review of the latest developments in nuclear chemistry. Nuclear research today is directed toward increased activity in radiopharmaceuticals and formation of new isotopes by high-energy, heavy-ion collisions. (Author/BB)

  12. Nuclear Scans

    MedlinePlus

    Nuclear scans use radioactive substances to see structures and functions inside your body. They use a special ... images. Most scans take 20 to 45 minutes. Nuclear scans can help doctors diagnose many conditions, including ...

  13. Nuclear Fuels.

    ERIC Educational Resources Information Center

    Nash, J. Thomas

    1983-01-01

    Trends in and factors related to the nuclear industry and nuclear fuel production are discussed. Topics addressed include nuclear reactors, survival of the U.S. uranium industry, production costs, budget cuts by the Department of Energy and U.S. Geological survey for resource studies, mining, and research/development activities. (JN)

  14. Nuclear weapons, nuclear effects, nuclear war

    SciTech Connect

    Bing, G.F.

    1991-08-20

    This paper provides a brief and mostly non-technical description of the militarily important features of nuclear weapons, of the physical phenomena associated with individual explosions, and of the expected or possible results of the use of many weapons in a nuclear war. Most emphasis is on the effects of so-called ``strategic exchanges.``

  15. Synthesis, structural characterization and DFT calculation on a square-planar Ni(II) complex of a compartmental Schiff base ligand

    NASA Astrophysics Data System (ADS)

    Biswas, Surajit; Dolai, Malay; Dutta, Arpan; Ali, Mahammad

    2016-12-01

    Reaction of a symmetric compartmental Schiff-base ligand, (H2L) with nickel(II) perchlorate hexahydrate in 1:1 M ratio in methanol gives rise to a mononuclear nickel(II) compound, NiL (1). The compound has been characterized by C, H, N microanalyses and UV-Vis spectra. The single crystal X-ray diffraction studies reveal a square planar geometry around the Ni(II) center. The compound crystallizes in monoclinic system with space group C2/c with a = 21.6425(6), b = 9.9481(3), c = 13.1958(4) Å, β = 107.728(2)°, V = 2706.16(14) Å3 and Z = 4. Ground state DFT optimization and TDDFT calculations on the ligand and complex were performed to get their UV-Vis spectral pattern.

  16. Development of In Vitro-In Vivo Correlation/Relationship Modeling Approaches for Immediate Release Formulations Using Compartmental Dynamic Dissolution Data from “Golem”: A Novel Apparatus

    PubMed Central

    Čulen, Martin; Tuszyński, Paweł K.; Polak, Sebastian; Jachowicz, Renata; Mendyk, Aleksander; Dohnal, Jiří

    2015-01-01

    Different batches of atorvastatin, represented by two immediate release formulation designs, were studied using a novel dynamic dissolution apparatus, simulating stomach and small intestine. A universal dissolution method was employed which simulated the physiology of human gastrointestinal tract, including the precise chyme transit behavior and biorelevant conditions. The multicompartmental dissolution data allowed direct observation and qualitative discrimination of the differences resulting from highly pH dependent dissolution behavior of the tested batches. Further evaluation of results was performed using IVIVC/IVIVR development. While satisfactory correlation could not be achieved using a conventional deconvolution based-model, promising results were obtained through the use of a nonconventional approach exploiting the complex compartmental dissolution data. PMID:26120580

  17. Cooperative catalysis of noncompatible catalysts through compartmentalization: wacker oxidation and enzymatic reduction in a one-pot process in aqueous media.

    PubMed

    Sato, Hirofumi; Hummel, Werner; Gröger, Harald

    2015-04-01

    A Wacker oxidation using CuCl/PdCl2 as a catalyst system was successfully combined with an enzymatic ketone reduction to convert styrene enantioselectively into 1-phenylethanol in a one-pot process, although the two reactions conducted in aqueous media are not compatible due to enzyme deactivation by Cu ions. The one-pot feasibility was achieved via compartmentalization of the reactions. Conducting the Wacker oxidation in the interior of a polydimethylsiloxane thimble enables diffusion of only the organic substrate and product into the exterior where the biotransformation takes place. Thus, the Cu ions detrimental to the enzyme are withheld from the reaction media of the biotransformation. In this one-pot process, which formally corresponds to an asymmetric hydration of alkenes, a range of 1-arylethanols were formed with high conversions and 98-99 % ee. In addition, the catalyst system of the Wacker oxidation was recycled 15 times without significant decrease in conversion.

  18. A multi-stage compartmental model for HIV-infected individuals: II--application to insurance functions and health-care costs.

    PubMed

    Billard, L; Dayananda, P W A

    2014-03-01

    Stochastic population processes have received a lot of attention over the years. One approach focuses on compartmental modeling. Billard and Dayananda (2012) developed one such multi-stage model for epidemic processes in which the possibility that individuals can die at any stage from non-disease related causes was also included. This extra feature is of particular interest to the insurance and health-care industries among others especially when the epidemic is HIV/AIDS. Rather than working with numbers of individuals in each stage, they obtained distributional results dealing with the waiting time any one individual spent in each stage given the initial stage. In this work, the impact of the HIV/AIDS epidemic on several functions relevant to these industries (such as adjustments to premiums) is investigated. Theoretical results are derived, followed by a numerical study.

  19. Biodegradation of a mixture of the herbicides ametryn, and 2,4-dichlorophenoxyacetic acid (2,4-D) in a compartmentalized biofilm reactor.

    PubMed

    Sandoval-Carrasco, Carlos A; Ahuatzi-Chacón, Deifilia; Galíndez-Mayer, Juvencio; Ruiz-Ordaz, Nora; Juárez-Ramírez, Cleotilde; Martínez-Jerónimo, Fernando

    2013-10-01

    In this work, an efficient degradation process for the removal of 2,4-D and ametryn, together with organic and inorganic adjuvants used in the commercial formulations of both herbicides, was developed. Although both compounds are toxic for microbial communities, ametryn is markedly more toxic than 2,4-D. In spite of this, the microbial consortium used could resist loading rates up to 31.5 mg L(-1) d(-1) of ametryn, with removal efficiencies up to 97% for both herbicides. Thus, an alternative use of this consortium could be bioaugmentation, as a tool to protect the structure and function of an activated-sludge biota against ametryn or 2,4-D shock loads. The process was carried out in a lab-scale prototype of aerobic biobarrier constructed as a compartmentalized fixed film reactor with airlift recirculation of oxygenated liquid.

  20. In vitro digestion of short-dough biscuits enriched in proteins and/or fibres using a multi-compartmental and dynamic system (2): Protein and starch hydrolyses.

    PubMed

    Villemejane, C; Denis, S; Marsset-Baglieri, A; Alric, M; Aymard, P; Michon, C

    2016-01-01

    The influence of protein and/or fibre enrichment on the nutritional properties of biscuits was studied in terms of proteolysis and amylolysis. Biscuits were digested using a multi-compartmental and dynamic system that simulates the main physiological digestive functions of the upper tract of healthy adult humans: the TIM-1. A control biscuit and three biscuits enriched in proteins and/or fibres were digested under the same conditions. Samples were collected in each compartment of the TIM-1 (stomach, duodenum, jejunum and ileum) at different times of digestion and analysed in terms of proteolysis and amylolysis. Results indicate that both formulation and processing impacted the digestive fate of the biscuits. Incorporating proteins or fibres in biscuits lowered or delayed proteolysis. Moreover a protein-plus-fibre additional or synergic effect was observed. Biscuits enriched in proteins and/or fibres displayed a higher amylolysis degree than the control biscuit, probably due to lower starch amounts and higher gelatinization degrees.

  1. Cause and Consequence of Tethering a SubTAD to Different Nuclear Compartments.

    PubMed

    Wijchers, Patrick J; Krijger, Peter H L; Geeven, Geert; Zhu, Yun; Denker, Annette; Verstegen, Marjon J A M; Valdes-Quezada, Christian; Vermeulen, Carlo; Janssen, Mark; Teunissen, Hans; Anink-Groenen, Lisette C M; Verschure, Pernette J; de Laat, Wouter

    2016-02-01

    Detailed genomic contact maps have revealed that chromosomes are structurally organized in megabase-sized topologically associated domains (TADs) that encompass smaller subTADs. These domains segregate in the nuclear space to form active and inactive nuclear compartments, but cause and consequence of compartmentalization are largely unknown. Here, we combined lacO/lacR binding platforms with allele-specific 4C technologies to track their precise position in the three-dimensional genome upon recruitment of NANOG, SUV39H1, or EZH2. We observed locked genomic loci resistant to spatial repositioning and unlocked loci that could be repositioned to different nuclear subcompartments with distinct chromatin signatures. Focal protein recruitment caused the entire subTAD, but not surrounding regions, to engage in new genomic contacts. Compartment switching was found uncoupled from transcription changes, and the enzymatic modification of histones per se was insufficient for repositioning. Collectively, this suggests that trans-associated factors influence three-dimensional compartmentalization independent of their cis effect on local chromatin composition and activity. PMID:26833089

  2. Cause and Consequence of Tethering a SubTAD to Different Nuclear Compartments

    PubMed Central

    Wijchers, Patrick J.; Krijger, Peter H.L.; Geeven, Geert; Zhu, Yun; Denker, Annette; Verstegen, Marjon J.A.M.; Valdes-Quezada, Christian; Vermeulen, Carlo; Janssen, Mark; Teunissen, Hans; Anink-Groenen, Lisette C.M.; Verschure, Pernette J.; de Laat, Wouter

    2016-01-01

    Summary Detailed genomic contact maps have revealed that chromosomes are structurally organized in megabase-sized topologically associated domains (TADs) that encompass smaller subTADs. These domains segregate in the nuclear space to form active and inactive nuclear compartments, but cause and consequence of compartmentalization are largely unknown. Here, we combined lacO/lacR binding platforms with allele-specific 4C technologies to track their precise position in the three-dimensional genome upon recruitment of NANOG, SUV39H1, or EZH2. We observed locked genomic loci resistant to spatial repositioning and unlocked loci that could be repositioned to different nuclear subcompartments with distinct chromatin signatures. Focal protein recruitment caused the entire subTAD, but not surrounding regions, to engage in new genomic contacts. Compartment switching was found uncoupled from transcription changes, and the enzymatic modification of histones per se was insufficient for repositioning. Collectively, this suggests that trans-associated factors influence three-dimensional compartmentalization independent of their cis effect on local chromatin composition and activity. PMID:26833089

  3. Development and Evaluation of a Compartmental Picture Archiving and Communications System Model for Integration and Visualization of Multidisciplinary Biomedical Data to Facilitate Student Learning in an Integrative Health Clinic

    ERIC Educational Resources Information Center

    Chow, Meyrick; Chan, Lawrence

    2010-01-01

    Information technology (IT) has the potential to improve the clinical learning environment. The extent to which IT enhances or detracts from healthcare professionals' role performance can be expected to affect both student learning and patient outcomes. This study evaluated nursing students' satisfaction with a novel compartmental Picture…

  4. Work-Related Pain in Extrinsic Finger Extensor Musculature of Instrumentalists Is Associated with Intracellular pH Compartmentation during Exercise

    PubMed Central

    Moreno-Torres, Angel; Rosset-Llobet, Jaume; Pujol, Jesus; Fàbregas, Sílvia; Gonzalez-de-Suso, Jose-Manuel

    2010-01-01

    Background Although non-specific pain in the upper limb muscles of workers engaged in mild repetitive tasks is a common occupational health problem, much is unknown about the associated structural and biochemical changes. In this study, we compared the muscle energy metabolism of the extrinsic finger extensor musculature in instrumentalists suffering from work-related pain with that of healthy control instrumentalists using non-invasive phosphorus magnetic resonance spectroscopy (31P-MRS). We hypothesize that the affected muscles will show alterations related with an impaired energy metabolism. Methodology/Principal Findings We studied 19 volunteer instrumentalists (11 subjects with work-related pain affecting the extrinsic finger extensor musculature and 8 healthy controls). We used 31P-MRS to find deviations from the expected metabolic response to exercise in phosphocreatine (PCr), inorganic phosphate (Pi), Pi/PCr ratio and intracellular pH kinetics. We observed a reduced finger extensor exercise tolerance in instrumentalists with myalgia, an intracellular pH compartmentation in the form of neutral and acid compartments, as detected by Pi peak splitting in 31P-MRS spectra, predominantly in myalgic muscles, and a strong association of this pattern with the condition. Conclusions/Significance Work-related pain in the finger extrinsic extensor muscles is associated with intracellular pH compartmentation during exercise, non-invasively detectable by 31P-MRS and consistent with the simultaneous energy production by oxidative metabolism and glycolysis. We speculate that a deficit in energy production by oxidative pathways may exist in the affected muscles. Two possible explanations for this would be the partial and/or local reduction of blood supply and the reduction of the muscle oxidative capacity itself. PMID:20161738

  5. Compartmentalization of the chick cerebellar cortex based on the link between the striped expression pattern of aldolase C and the topographic olivocerebellar projection.

    PubMed

    Vibulyaseck, Suteera; Luo, Yuanjun; Fujita, Hirofumi; Oh-Nishi, Arata; Ohki-Hamazaki, Hiroko; Sugihara, Izumi

    2015-09-01

    The avian cerebellum is organized into multiple longitudinal stripes defined by expression profiles of aldolase C (zebrin II) in Purkinje cells. The relationship between the aldolase C striped pattern and the olivocerebellar projection pattern is crucial in understanding cerebellar functional compartmentalization. We identified all aldolase C stripes across all lobules with the serial section alignment analysis method and then looked at this relationship by anterograde and retrograde labeling of olivocerebellar axons in the chick cerebellum. Aldolase C stripes were generally consistent and continuous from lobule I through VII and to the medial part of lobules VIII-IXb. The dorsal and ventral lamellas (DL, VL) of the inferior olive projected to the stripes in these areas with a simple mediolateral topographic relation. A few aldolase C stripes appeared at the lateral edge of lobules VI-VIII. Several more stripes were added in the lateral parts of lobules IXa-IXb and IXc-X. The medial column (MC) of the inferior olive projected to the stripes in lobules VIII-X, including the added lateral stripes, with a complex topographic relation. Sharp boundaries between aldolase C-positive and -negative stripes often accompanied a gap in the Purkinje cell layer and bordered topographically distinct groups of axons. Although the compartmental organization of the chick cerebellum is comparable to that of the mammalian cerebellum, several significant differences in the organization suggest partly separate evolutionary lineages of the mammalian and avian cerebella. We propose that rostral lobules may be evolved by rostral extension of medial stripes from caudal lobules in the avian cerebellum.

  6. Surface adsorption, intracellular accumulation and compartmentalization of Pb(II) in batch-operated lagoons with Salvinia minima as affected by environmental conditions, EDTA and nutrients.

    PubMed

    Olguín, Eugenia J; Sánchez-Galván, Gloria; Pérez-Pérez, Teresa; Pérez-Orozco, Arith

    2005-12-01

    The effects of environmental factors and nutrients on the various possible removal mechanisms (surface adsorption, intracellular accumulation and precipitation to sediments) and partitioning of lead among various compartments (plant biomass, water column and sediments) in Salvinia minima batch-operated lagoons, were evaluated. Surface adsorption was found to be the predominant mechanism for Pb(II) removal under all environmental conditions tested in the absence of nutrients (an average of 54.3%) and in a nutrient medium (modified Hutner 1/10 medium) free of EDTA and phosphates (54.41%) at "high" initial Pb(II) concentrations (in the range of 10.3+/-0.13 to 15.2+/-0.05 mg/L). Under these conditions, the bioconcentration factors (BCFs) were 2,431+/-276 and 2,065+/-35, respectively. Lead removal was very rapid during the first 4 h and reached 70% in the absence of nutrients at the "medium" light intensity and temperature (LIT) tested, 88% in nutrient medium free of EDTA and supplemented with synthetic wastewater (at the "lowest" LIT tested), and 85% in medium free of EDTA and phosphates. It was concluded that the mechanisms of lead removal by S. minima, and the compartmentalization of this metal in the microcosm of batch-operated lagoons, are primarily a function of the presence of certain nutrients and chelants, with secondary dependence on environmental conditions. In addition, the results indicate that the percentage of lead removed is only a gross parameter and that the complementary use of BCF and compartmentalization analysis is required to gain a full insight into the metal removal process.

  7. Amazing courage in the Calais 'Jungle'.

    PubMed

    Howe, Holly

    2016-02-10

    Staff nurse Holly Howe completed a six-week volunteer placement at the Calais migrant camp’s clinic. She found the work heartbreaking, but was amazed by the resilience of the people living in the camp.

  8. From Answer Garden to Answer Jungle.

    ERIC Educational Resources Information Center

    Dron, Jon; Mitchell, Richard; Siviter, Phil

    1998-01-01

    The use of Usenet newsgroups in a computing and information systems classroom at the University of Brighton showed how Internet-based learning systems can encourage rapid evolution so that resources adapt to learners' needs. Although not always used as intended, and including off-topic distractions, newsgroups did accommodate learning styles and…

  9. The chemical jungle: today's beef industry.

    PubMed

    Epstein, S S

    1990-01-01

    In the absence of effective federal regulation, the meat industry uses hundreds of animal feed additives, including antibiotics, tranquilizers, pesticides, animal drugs, artificial flavors, industrial wastes, and growth-promoting hormones, with little or no concern about the carcinogenic and other toxic effects of dietary residues of these additives. Illustratively, after decades of misleading assurances of the safety of diethylstilbestrol (DES) and its use as a growth-promoting animal-feed additive, the United States finally banned its use in 1979 some 40 years after it was first shown to be carcinogenic. The meat industry then promptly switched to other carcinogenic additives, particularly the natural sex hormones estradiol, progesterone, and testosterone, which are implanted in the ears of more than 90 percent of commercially raised feedlot cattle. Unlike the synthetic DES, residues of which can be monitored and use of which was conditional on a seven-day preslaughter withdrawal period, residues of natural hormones are not detectable, since they cannot be practically differentiated from the same hormones produced by the body. The relationship between recently increasing cancer rates and the lifetime exposure of the U.S. population to dietary residues of these and other unlabeled carcinogenic feed additives is a matter of critical public health concern. PMID:2332262

  10. Ivory Tower to Concrete Jungle Revisited

    ERIC Educational Resources Information Center

    Crebert, Gay; Bates, Merrelyn; Bell, Barry; Patrick, Carol-Joy; Cragnolini, Vanda

    2004-01-01

    In 2001-02, a project team at Griffith University undertook Stage 4 of the Griffith Graduate Project. Stage 4 used a survey and focus group discussions to gather graduates' and employers' perceptions of the role of the university, work placements and postgraduation employment in the development of generic skills and abilities. This article will…

  11. Celtic Tiger Found in Education Jungle

    ERIC Educational Resources Information Center

    Cooney, Thomas M.

    2008-01-01

    Purpose: While the growth of the Irish economy ("Celtic Tiger") has been well documented, not enough attention has been given to the role of education as a cornerstone for the success. This paper seeks to review education policy in Ireland over the past 50 years and to identify the significant educational initiatives that helped shape modern…

  12. Navigating Your Way through the Research Jungle

    ERIC Educational Resources Information Center

    Bauer, Scott; Brazer, David

    2012-01-01

    These days, information overload seems to be the normal state of existence. School leaders are inundated with descriptions of best practices and programs that work. They are exhorted to use evidence in all facets of decision-making and to employ research-based strategies to improve schools. Of course, research findings are seldom definitive, and…

  13. Pipeliners beat designers across Panama's jungle

    SciTech Connect

    Not Available

    1982-05-27

    Hard-driving pipeline crews are slashing a path down the steep slopes of the Andes range on Panama's Caribbean coast for the final leg of an 80-mile Pacific-Atlantic oil link that will reduce shipping times for North Slope crude to Gulf Coast refineries. When completed in late August, the trans-isthmus tube will be able to drain the Panama Canal of Alaskan oil, which currently must be pumped from large tankers to 65,000 ton ships before passage through the 50-mile cut. The 36 and 40-in.-dia pipe will connect an existing Northville oil transshipment terminal at Puerto Armuelles, near Costa Rica on the Pacific Coast, with a new 2.5-million-bbl storage area at Chiriqui Grande on the Caribbean coast. Two pumping stations, one at Puerto Armuelles and another at the base of the Serrania de Tabasara mountains, will lift the oil 4,000 ft over the Continental Divide. Gravity flows of 7 1/2 ft per second down the steep drop to the swamps along the Caribbean will feed three 833,000-bbl tanks being built on a hillside overlooking Chiriqui Bay. From there, two 36-in. lines will feed concrete-coated pipe sections trenched into the surf zone and placed on the muddy bottom for the remaining distance to two marine loading buoys over a mile offshore. The catenary anchor-leg mooring buoys are designed to handle tankers of up to 160,000 tons in 65 ft of water at maximum fill rates of 120,000 bbl per hour.

  14. Jungle in the heart of the city

    NASA Astrophysics Data System (ADS)

    Kolodziejska, Magdalena; Czerniak-Czyzniak, Marta

    2015-04-01

    Lessons of nature can be an interesting adventure for students if we allow them to actively participate in such activities. Students must engage in educational activities but thanks to them they also better absorb more knowledge and abilities. These types of activities also require proper preparation of the teacher, who should first get to know the area and next prepare a plan for the trip and also define objectives, tasks and issues that confront students. By providing such training for teachers, you can show various methods and forms of work, which allow to use the resources of the local environment. The area of the Vistula River is such an amazing place in Warsaw (capital of Poland). The phenomenon of this place is its wildness in the heart of the city. Fortunately, urbanization has not destroyed its wildness. Teachers are encouraged to use these unique resources in working with students. During the training they receive information and tools that help them to carry out such activities. Outdoor activities give possibility for cross subjects integration that is essential in modern teaching because in this place the content of different subjects complement each other. During these classes students gain not only the theoretical knowledge but also a comprehensive knowledge and intelligently learn the world around us and experience the processes occurring in the natural environment and cultural heritage. Interesting outdoor activities affect the growth of motivation of young people and affect their interest in natural subjects. During outdoor activities they observe the processes and phenomena in the natural place of their occurrence. Such activities can be treated both as providing the general overview for certain topics as well as its deepening. Students during an outdoor activity acquire abilities and improve practical skills. Also important is the ability to pursue educational goals. Observing the environment, students learn the culture of communing with nature. Outdoor activities shape students attitudes and beliefs about the need for rational management of natural resources and to join the efforts for nature and the environment. You cannot here omit the fact that the students often during communication with nature can establish strong emotional ties, he/she becomes sensitive to its beauty, also convinced of the need to protect the environment and most importantly can feel partly responsible for her condition. Outdoor activities engage all students to work and not just the most talented. It also allows for direct contact with the environment, offers the possibility of physical activity in the open air, allows for involvement of all sense receptors and thus are recognized by students, regardless of their age, for the most attractive. According to Piaget's theory "Thanks to activity in the external world a child (person) achieves the knowledge of the methods and regularities of its functioning". The author points out how important is to teach by an action especially when the student alone can experience the world around him/her.

  15. Tracking hippo in the cancer jungle.

    PubMed

    Suh, Jung H; Saba, Julie D

    2014-07-17

    Signaling through the Hippo pathway controls major aspects of cell growth and proliferation. Focusing on the metabolic consequences of Hippo signaling, Mulvihill and colleagues in this issue of Chemistry & Biology employ a large scale, integrative approach and uncover downstream reorganization of cellular metabolism when the effector TAZ is upregulated, identifying new connections to lipid metabolism.

  16. Nuclear asynchrony in multinucleate rat kangaroo cells.

    PubMed

    Ghosh, S; Paweletz, N

    1984-11-01

    Multinucleate (MN) cells were induced in PtK1 cells by colcemid treatment. A large percentage of cells developed nuclear asynchrony both in relation to DNA synthesis and mitosis within one cell cycle. Asynchrony could be traced even in metaphase and anaphase cells in which interphase nuclei, PCC of S-phase nuclei and less condensed prophase-like chromosomes could be observed along with normally condensed chromosomes. The occurrence of such abnormalities in these large MN cells may be explained on the basis of an uneven distribution of inducer molecules of DNA synthesis and mitosis due to cytoplasmic compartmentation. The less condensed form of all the chromosomes except chromosome 4 could be traced in asynchronous metaphase. The failure of the less condensed chromosomes to undergo complete condensation does not always appear to result from late entry of nuclei containing these chromosomes into G2 phase. It is likely that chromosome 4 carries gene(s) for chromosome condensation, as this chromosome itself never appears in a less condensed form. The inducers for chromosome condensation may not always be available at equal concentrations to all chromosomes located in separate nuclei, thus they may sometimes fail to undergo complete condensation before other nuclei reach the end of prophase, when the nuclear envelopes of all nuclei present in the cell break down simultaneously.

  17. SRSF1 regulates the assembly of pre-mRNA processing factors in nuclear speckles.

    PubMed

    Tripathi, Vidisha; Song, David Y; Zong, Xinying; Shevtsov, Sergey P; Hearn, Stephen; Fu, Xiang-Dong; Dundr, Miroslav; Prasanth, Kannanganattu V

    2012-09-01

    The mammalian cell nucleus is compartmentalized into nonmembranous subnuclear domains that regulate key nuclear functions. Nuclear speckles are subnuclear domains that contain pre-mRNA processing factors and noncoding RNAs. Many of the nuclear speckle constituents work in concert to coordinate multiple steps of gene expression, including transcription, pre-mRNA processing and mRNA transport. The mechanism that regulates the formation and maintenance of nuclear speckles in the interphase nucleus is poorly understood. In the present study, we provide evidence for the involvement of nuclear speckle resident proteins and RNA components in the organization of nuclear speckles. SR-family splicing factors and their binding partner, long noncoding metastasis-associated lung adenocarcinoma transcript 1 RNA, can nucleate the assembly of nuclear speckles in the interphase nucleus. Depletion of SRSF1 in human cells compromises the association of splicing factors to nuclear speckles and influences the levels and activity of other SR proteins. Furthermore, on a stably integrated reporter gene locus, we demonstrate the role of SRSF1 in RNA polymerase II-mediated transcription. Our results suggest that SR proteins mediate the assembly of nuclear speckles and regulate gene expression by influencing both transcriptional and posttranscriptional activities within the cell nucleus.

  18. The transmission of nuclear pore complexes to daughter cells requires a cytoplasmic pool of Nsp1.

    PubMed

    Colombi, Paolo; Webster, Brant M; Fröhlich, Florian; Lusk, C Patrick

    2013-10-28

    Nuclear pore complexes (NPCs) are essential protein assemblies that span the nuclear envelope and establish nuclear-cytoplasmic compartmentalization. We have investigated mechanisms that control NPC number in mother and daughter cells during the asymmetric division of budding yeast. By simultaneously tracking existing NPCs and newly synthesized NPC protomers (nups) through anaphase, we uncovered a pool of the central channel nup Nsp1 that is actively targeted to the bud in association with endoplasmic reticulum. Bud targeting required an intact actin cytoskeleton and the class V myosin, Myo2. Selective inhibition of cytoplasmic Nsp1 or inactivation of Myo2 reduced the inheritance of NPCs in daughter cells, leading to a daughter-specific loss of viability. Our data are consistent with a model in which Nsp1 releases a barrier that otherwise prevents NPC passage through the bud neck. It further supports the finding that NPC inheritance, not de novo NPC assembly, is primarily responsible for controlling NPC number in daughter cells.

  19. Nuclear Matrix protein SMAR1 represses HIV-1 LTR mediated transcription through chromatin remodeling

    SciTech Connect

    Sreenath, Kadreppa; Pavithra, Lakshminarasimhan; Singh, Sandeep; Sinha, Surajit; Dash, Prasanta K.; Siddappa, Nagadenahalli B.; Ranga, Udaykumar; Mitra, Debashis; Chattopadhyay, Samit

    2010-04-25

    Nuclear Matrix and MARs have been implicated in the transcriptional regulation of host as well as viral genes but their precise role in HIV-1 transcription remains unclear. Here, we show that > 98% of HIV sequences contain consensus MAR element in their promoter. We show that SMAR1 binds to the LTR MAR and reinforces transcriptional silencing by tethering the LTR MAR to nuclear matrix. SMAR1 associated HDAC1-mSin3 corepressor complex is dislodged from the LTR upon cellular activation by PMA/TNFalpha leading to an increase in the acetylation and a reduction in the trimethylation of histones, associated with the recruitment of RNA Polymerase II on the LTR. Overexpression of SMAR1 lead to reduction in LTR mediated transcription, both in a Tat dependent and independent manner, resulting in a decreased virion production. These results demonstrate the role of SMAR1 in regulating viral transcription by alternative compartmentalization of LTR between the nuclear matrix and chromatin.

  20. Nuclear mortality

    SciTech Connect

    Krauthammer, C.

    1983-10-01

    The author notes that the anti-nuclear movement is shifting its focus from bodily harm to concern for the impact on our souls from building and threatening the use of nuclear weapons. Two aspects of nuclear deterrence receiving the most public attention are the freeze effort to halt weapons modernization and the no-first-use effort to take down the nuclear umbrella. Opponents attack both the countervalue and the counterforce approach, but the arguments of the Catholic bishops, Jonathan Schell, and others stop short of unilateral disarmament, which would be the greatest threat to our survival. Mr. Krauthammer observes that nuclear deterrence has worked, however, and will continue to be useful only if potential adversaries believe we have the will to use nuclear weapons. 2 references. (DCK)

  1. Nuclear astrophysics

    SciTech Connect

    Haxton, W.C.

    1992-01-01

    The problem of core-collapse supernovae is used to illustrate the many connections between nuclear astrophysics and the problems nuclear physicists study in terrestrial laboratories. Efforts to better understand the collapse and mantle ejection are also motivated by a variety of interdisciplinary issues in nuclear, particle, and astrophysics, including galactic chemical evolution, neutrino masses and mixing, and stellar cooling by the emission of new particles. The current status of theory and observations is summarized.

  2. Nuclear astrophysics

    SciTech Connect

    Haxton, W.C.

    1992-12-31

    The problem of core-collapse supernovae is used to illustrate the many connections between nuclear astrophysics and the problems nuclear physicists study in terrestrial laboratories. Efforts to better understand the collapse and mantle ejection are also motivated by a variety of interdisciplinary issues in nuclear, particle, and astrophysics, including galactic chemical evolution, neutrino masses and mixing, and stellar cooling by the emission of new particles. The current status of theory and observations is summarized.

  3. Nuclear Astrophysics

    NASA Astrophysics Data System (ADS)

    Drago, Alessandro

    2005-04-01

    The activity of the Italian nuclear physicists community in the field of Nuclear Astrophysics is reported. The researches here described have been performed within the project "Fisica teorica del nucleo e dei sistemi a multi corpi", supported by the Ministero dell'Istruzione, dell'Università e della Ricerca.

  4. Nuclear safety

    NASA Technical Reports Server (NTRS)

    Buden, D.

    1991-01-01

    Topics dealing with nuclear safety are addressed which include the following: general safety requirements; safety design requirements; terrestrial safety; SP-100 Flight System key safety requirements; potential mission accidents and hazards; key safety features; ground operations; launch operations; flight operations; disposal; safety concerns; licensing; the nuclear engine for rocket vehicle application (NERVA) design philosophy; the NERVA flight safety program; and the NERVA safety plan.

  5. Nuclear hostages

    SciTech Connect

    O'Keefe, B.J.

    1983-01-01

    Classical physics since Roentgen's discovery of X-rays led quickly to work on atomic structure and the Nuclear Age. The author traces the history of decisions to pursue nuclear fission, the organization of the Manhattan Project, the compromises of the 1963 test ban treaty, and the dilemma of nuclear weapons development and deployment that now hold mankind hostage. He reviews the rationale for limited nuclear war, first strike, massive retaliation, non-proliferation, and the Strategic Arms Limitation Talks (SALT) treaties. He argues that the concepts of mobile MX weapons, fratricide, and population dispersal for civil defense are unworkable, suggesting a program of unilaterally withdrawing tactical nuclear weapons from Europe and strengthening intelligence and law-enforcement powers to withstand terrorist activity. Economic cooperation and political reconciliation may take a generation to achieve, but should be our national goal.

  6. AAGAG repeat RNA is an essential component of nuclear matrix in Drosophila

    PubMed Central

    Pathak, Rashmi U.; Mamillapalli, Anitha; Rangaraj, Nandini; Kumar, Ram P.; Vasanthi, Dasari; Mishra, Krishnaveni; Mishra, Rakesh K.

    2013-01-01

    Eukaryotic nucleus is functionally as well as spatially compartmentalized and maintains dynamic organization of sub-nuclear bodies. This organization is supported by a non-chromatin nuclear structure called the nuclear matrix. Although the precise molecular composition and ultra-structure of the nuclear matrix is not known, proteins and RNA molecules are its major components and several nuclear matrix proteins have been identified. However, the nature of its RNA component is unknown. Here we show that in Drosophila melanogaster, transcripts from AAGAG repeats of several hundred nucleotide in length are critical constituents of the nuclear matrix. While both the strands of this repeat are transcribed and are nuclear matrix associated, the polypurine strand is predominantly detected in situ. We also show that AAGAG RNA is essential for viability. Our results reveal the molecular identity of a critical RNA component of the nuclear architecture and point to one of the utilities of the repetitive part of the genome that has accumulated in higher eukaryotes. PMID:23588056

  7. New quantitative approaches reveal the spatial preference of nuclear compartments in mammalian fibroblasts.

    PubMed

    Weston, David J; Russell, Richard A; Batty, Elizabeth; Jensen, Kirsten; Stephens, David A; Adams, Niall M; Freemont, Paul S

    2015-03-01

    The nuclei of higher eukaryotic cells display compartmentalization and certain nuclear compartments have been shown to follow a degree of spatial organization. To date, the study of nuclear organization has often involved simple quantitative procedures that struggle with both the irregularity of the nuclear boundary and the problem of handling replicate images. Such studies typically focus on inter-object distance, rather than spatial location within the nucleus. The concern of this paper is the spatial preference of nuclear compartments, for which we have developed statistical tools to quantitatively study and explore nuclear organization. These tools combine replicate images to generate 'aggregate maps' which represent the spatial preferences of nuclear compartments. We present two examples of different compartments in mammalian fibroblasts (WI-38 and MRC-5) that demonstrate new knowledge of spatial preference within the cell nucleus. Specifically, the spatial preference of RNA polymerase II is preserved across normal and immortalized cells, whereas PML nuclear bodies exhibit a change in spatial preference from avoiding the centre in normal cells to exhibiting a preference for the centre in immortalized cells. In addition, we show that SC35 splicing speckles are excluded from the nuclear boundary and localize throughout the nucleoplasm and in the interchromatin space in non-transformed WI-38 cells. This new methodology is thus able to reveal the effect of large-scale perturbation on spatial architecture and preferences that would not be obvious from single cell imaging.

  8. Specific binding of [(18)F]fluoroethyl-harmol to monoamine oxidase A in rat brain cryostat sections, and compartmental analysis of binding in living brain.

    PubMed

    Maschauer, Simone; Haller, Adelina; Riss, Patrick J; Kuwert, Torsten; Prante, Olaf; Cumming, Paul

    2015-12-01

    We investigated [(18)F]fluoroethyl-harmol ([(18)F]FEH) as a reversible and selective ligand for positron emission tomography (PET) studies of monoamine oxidase A (MAO-A). Binding of [(18)F]FEH in rat brain cryostat sections indicated high affinity (KD = 3 nM), and density (Bmax; 600 pmol/g). The plasma free fraction was 45%, and untransformed parent constituted only 13% of plasma radioactivity at 10 min after injection. Compartmental analysis of PET recordings in pargyline-treated rats showed high permeability to brain (K1; 0.32 mL/g/min) and slow washout (k2; 0.024/min), resulting in a uniformly high equilibrium distribution volume (VD; 20 mL/g). Using this VD to estimate unbound ligand in brain of untreated rats, the binding potential ranged from 4.2 in cerebellum to 7.2 in thalamus. We also calculated maps of rats receiving [(18)F]FEH at a range of specific activities, and then estimated saturation binding parameters in the living brain. In thalamus, striatum and frontal cortex KD was globally close to 300 nM and Bmax was close to 1600 pmol/g; the 100-fold discrepancy in affinity suggests a very low free fraction for [(18)F]FEH in the living brain. Based on a synthesis of findings, we calculate the endogenous dopamine concentration to be 0.4 μM in the striatal compartment containing MAO-A, thus unlikely to exert competition against [(18)F]FEH binding in vivo. In summary, [(18)F]FEH has good properties for the detection of MAO-A in the rat brain by PET, and may present logistic advantages for clinical research at centers lacking a medical cyclotron. We made a compartmental analysis of [(18)F]fluoroethylharmol ([(18)F]FEH) binding to monoamine oxidase A (MAO-A) in living rat brain and estimated the saturation binding parameters from the binding potential (BPND). The Bmax was of comparable magnitude to that in vitro, but with apparent affinity (300 nM), it was 100-fold lower in vivo. PET imaging with [(18) F]FEH is well suited for quantitation of MAO-A in living

  9. Cytoplasmic localization of Hug1p, a negative regulator of the MEC1 pathway, coincides with the compartmentalization of Rnr2p–Rnr4p

    SciTech Connect

    Ainsworth, William B.; Hughes, Bridget Todd; Au, Wei Chun; Sakelaris, Sally; Kerscher, Oliver; Benton, Michael G.; Basrai, Munira A.

    2013-10-04

    Highlights: •Hug1p overexpression sensitizes wild-type cells to DNA damage and hydroxyurea (HU). •Expression of Hug1p in response to HU treatment is delayed relative to Rnr3p. •MEC1 pathway genes are required for cytoplasmic localization of Hug1p. •Hug1p subcellular compartmentalization to the cytoplasm coincides with Rnr2p–Rnr4p. -- Abstract: The evolutionarily conserved MEC1 checkpoint pathway mediates cell cycle arrest and induction of genes including the RNR (Ribonucleotide reductase) genes and HUG1 (Hydroxyurea, ultraviolet, and gamma radiation) in response to DNA damage and replication arrest. Rnr complex activity is in part controlled by cytoplasmic localization of the Rnr2p–Rnr4p subunits and inactivation of negative regulators Sml1p and Dif1p upon DNA damage and hydroxyurea (HU) treatment. We previously showed that a deletion of HUG1 rescues lethality of mec1Δ and suppresses dun1Δ strains. In this study, multiple approaches demonstrate the regulatory response of Hug1p to DNA damage and HU treatment and support its role as a negative effector of the MEC1 pathway. Consistent with our hypothesis, wild-type cells are sensitive to DNA damage and HU when HUG1 is overexpressed. A Hug1 polyclonal antiserum reveals that HUG1 encodes a protein in budding yeast and its MEC1-dependent expression is delayed compared to the rapid induction of Rnr3p in response to HU treatment. Cell biology and subcellular fractionation experiments show localization of Hug1p-GFP to the cytoplasm upon HU treatment. The cytoplasmic localization of Hug1p-GFP is dependent on MEC1 pathway genes and coincides with the cytoplasmic localization of Rnr2p–Rnr4p. Taken together, the genetic interactions, gene expression, and localization studies support a novel role for Hug1p as a negative regulator of the MEC1 checkpoint response through its compartmentalization with Rnr2p–Rnr4p.

  10. Nuclear Astrophysics

    NASA Astrophysics Data System (ADS)

    Bombaci, Ignazio

    2003-04-01

    In this report I will try to illustrate some of the main research themes and "hot topics" in nuclear astrophysics. The particular aim of the present report is to briefly illustrate the research activities, in the field of nuclear astrophysics, performed by the Italian nuclear physicist community within the "Programma di Interesse Nazionale su Fisica Teorica del Nucleo e dei Sistemi a Molti Corpi" (National Research Program on Theoretical Physics of Nuclei and Many Body Systems) supported by the "Ministero dell'Istruzione dell'Università e della Ricerca".

  11. Nuclear Speckles

    PubMed Central

    Spector, David L.; Lamond, Angus I.

    2011-01-01

    Nuclear speckles, also known as interchromatin granule clusters, are nuclear domains enriched in pre-mRNA splicing factors, located in the interchromatin regions of the nucleoplasm of mammalian cells. When observed by immunofluorescence microscopy, they usually appear as 20–50 irregularly shaped structures that vary in size. Speckles are dynamic structures, and their constituents can exchange continuously with the nucleoplasm and other nuclear locations, including active transcription sites. Studies on the composition, structure, and dynamics of speckles have provided an important paradigm for understanding the functional organization of the nucleus and the dynamics of the gene expression machinery. PMID:20926517

  12. (Nuclear theory). [Research in nuclear physics

    SciTech Connect

    Haxton, W.

    1990-01-01

    This report discusses research in nuclear physics. Topics covered in this paper are: symmetry principles; nuclear astrophysics; nuclear structure; quark-gluon plasma; quantum chromodynamics; symmetry breaking; nuclear deformation; and cold fusion. (LSP)

  13. Compartmental analysis of washout effect in rat brain: in-beam OpenPET measurement using a 11C beam

    NASA Astrophysics Data System (ADS)

    Hirano, Yoshiyuki; Kinouchi, Shoko; Ikoma, Yoko; Yoshida, Eiji; Wakizaka, Hidekazu; Ito, Hiroshi; Yamaya, Taiga

    2013-12-01

    In-beam positron emission tomography (PET) is expected to enable visualization of a dose verification using positron emitters (β+ decay). For accurate dose verification, correction of the washout of the positron emitters should be made. In addition, the quantitative washout rate has a potential usefulness as a diagnostic index, but modeling for this has not been studied yet. In this paper, therefore, we applied compartment analyses to in-beam PET data acquired by our small OpenPET prototype, which has a physically opened field-of-view (FOV) between two detector rings. A rat brain was located at the FOV and was irradiated by a 11C beam. Time activity curves of the irradiated field were measured immediately after the irradiations, and the washout rate was obtained based on two models: the two-washout model (medium decay, k2m; slow decay, k2s) developed in a study of rabbit irradiation; and the two-compartment model used in nuclear medicine, where efflux from tissue to blood (k2), influx (k3) and efflux (k4) from the first to second compartments in tissue were evaluated. The observed k2m and k2s were 0.34 and 0.005 min-1, respectively, which was consistent with the rabbit study. Also k2m was close to the washout rate in cerebral blood flow (CBF) measurements by dynamic PET with 15O-water, while, k2, k3, and k4 were 0.16, 0.15 and 0.007 min-1. Our present work suggested the dynamics of 11C might be relevant to CBF or permeability of a molecule containing 11C atoms might be regulated by a transporter because the k2 was relatively low compared with a simple diffusion tracer.

  14. Nuclear forces

    SciTech Connect

    Machleidt, R.

    2013-06-10

    These lectures present an introduction into the theory of nuclear forces. We focus mainly on the modern approach, in which the forces between nucleons emerge from low-energy QCD via chiral effective field theory.

  15. Nuclear Disarmament.

    ERIC Educational Resources Information Center

    Johnson, Christopher

    1982-01-01

    Material about nuclear disarmament and the arms race should be included in secondary school curricula. Teachers can present this technical, controversial, and frightening material in a balanced and comprehensible way. Resources for instructional materials are listed. (PP)

  16. Nuclear battlefields

    SciTech Connect

    Arkin, W.M.; Fieldhouse, R.W.

    1985-01-01

    This book provides complete data on the nuclear operations and research facilities in the U.S.A., the U.S.S.R., France, China and the U.K. It describes detailed estimates on the U.S.S.R.'s nuclear stockpile for over 500 locations. It shows how non-nuclear countries cooperate with the world-wide war machine. And it maps the U.S. nuclear facilities from Little America, WY, and Charleston, SC, to the battleships patroling the world's oceans and subs stalking under the sea. The data were gathered from unclassified sources through the Freedom of Information Act, from data supplied to military installations, and from weapons source books. It provides guidance for policymakers, government and corporate officials.

  17. NUCLEAR REACTOR

    DOEpatents

    Sherman, J.; Sharbaugh, J.E.; Fauth, W.L. Jr.; Palladino, N.J.; DeHuff, P.G.

    1962-10-23

    A nuclear reactor incorporating seed and blanket assemblies is designed. Means are provided for obtaining samples of the coolant from the blanket assemblies and for varying the flow of coolant through the blanket assemblies. (AEC)

  18. Interaction of copper(II) complex of compartmental Schiff base ligand N, N'-bis(3-hydroxysalicylidene)ethylenediamine with bovine serum albumin

    NASA Astrophysics Data System (ADS)

    Boghaei, Davar M.; Farvid, Shokouh S.; Gharagozlou, Mehrnaz

    2007-03-01

    Circular dichroism (CD) spectroscopy, cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to investigate the interaction between copper(II) complex of compartmental Schiff base ligand (L), N, N'-bis(3-hydroxysalicylidene)ethylenediamine, and bovine serum albumin (BSA) in 0.1 mol dm -3 phosphate buffer solution adjusted to physiological pH 7.0 containing 20% (w/w) dimethylsulfoxide at room temperature. CD spectra show that the interaction of the copper(II) complex with BSA leads to changes in the α-helical content of BSA and therefore changes in secondary structure of the protein with the slight red shift (2 nm) in CD spectra. From the voltammetric data, i.e. changes in limiting current with addition of BSA, the binding constant ( K) of the interaction of copper(II) complex with BSA was found to be 1.96 × 10 4 dm 3 mol -1. From the shifts in potential with the addition of BSA, the equilibrium constant ratio ( K2/ K1) for the binding of the oxidized Cu IIL ( K1) and reduced Cu IL ( K2) species to BSA was found to be 3.77, which shows that the reduced form Cu IL is bound more strongly to BSA than the oxidized form Cu IIL.

  19. Compartmentalized self-replication under fast PCR cycling conditions yields Taq DNA polymerase mutants with increased DNA-binding affinity and blood resistance

    PubMed Central

    Arezi, Bahram; McKinney, Nancy; Hansen, Connie; Cayouette, Michelle; Fox, Jeffrey; Chen, Keith; Lapira, Jennifer; Hamilton, Sarah; Hogrefe, Holly

    2014-01-01

    Faster-cycling PCR formulations, protocols, and instruments have been developed to address the need for increased throughput and shorter turn-around times for PCR-based assays. Although run times can be cut by up to 50%, shorter cycle times have been correlated with lower detection sensitivity and increased variability. To address these concerns, we applied Compartmentalized Self Replication (CSR) to evolve faster-cycling mutants of Taq DNA polymerase. After five rounds of selection using progressively shorter PCR extension times, individual mutations identified in the fastest-cycling clones were randomly combined using ligation-based multi-site mutagenesis. The best-performing combinatorial mutants exhibit 35- to 90-fold higher affinity (lower Kd) for primed template and a moderate (2-fold) increase in extension rate compared to wild-type Taq. Further characterization revealed that CSR-selected mutations provide increased resistance to inhibitors, and most notably, enable direct amplification from up to 65% whole blood. We discuss the contribution of individual mutations to fast-cycling and blood-resistant phenotypes. PMID:25177317

  20. Building America Case Study: Apartment Compartmentalization with an Aerosol-Based Sealing Process - Queens, NY; Technology Solutions for New and Existing Homes, Energy Efficiency & Renewable Energy (EERE)

    SciTech Connect

    2015-07-01

    Air sealing of building enclosures is a difficult and time-consuming process. Current methods in new construction require laborers to physically locate small and sometimes large holes in multiple assemblies and then manually seal each of them. The innovation demonstrated under this research study was the automated air sealing and compartmentalization of buildings through the use of an aerosolized sealant, developed by the Western Cooling Efficiency Center at University of California Davis.
    CARB sought to demonstrate this new technology application in a multifamily building in Queens, NY. The effectiveness of the sealing process was evaluated by three methods: air leakage testing of overall apartment before and after sealing, point-source testing of individual leaks, and pressure measurements in the walls of the target apartment during sealing. Aerosolized sealing was successful by several measures in this study. Many individual leaks that are labor-intensive to address separately were well sealed by the aerosol particles. In addition, many diffuse leaks that are difficult to identify and treat were also sealed. The aerosol-based sealing process resulted in an average reduction of 71% in air leakage across three apartments and an average apartment airtightness of 0.08 CFM50/SF of enclosure area.

  1. Phagosomes induced by cytokines function as anti-Listeria vaccines: novel role for functional compartmentalization of STAT-1 protein and cathepsin-D.

    PubMed

    Carrasco-Marín, Eugenio; Rodriguez-Del Rio, Estela; Frande-Cabanes, Elisabet; Tobes, Raquel; Pareja, Eduardo; Lecea-Cuello, M Jesús; Ruiz-Sáez, Marta; Madrazo-Toca, Fidel; Hölscher, Christoph; Alvarez-Dominguez, Carmen

    2012-04-27

    Phagosomes are critical compartments for innate immunity. However, their role in the protection against murine listeriosis has not been examined. We describe here that listericidal phago-receptosomes are induced by the function of IFN-γ or IL-6 as centralized compartments for innate and adaptive immunity because they are able to confer protection against murine listeriosis. These phago-receptosomes elicited LLO(91-99)/CD8(+)- and LLO(189-201)/CD4(+)-specific immune responses and recruited mature dendritic cells to the vaccination sites controlled by T cells. Moreover, they present exceptional features as efficient vaccine vectors. First, they compartmentalize a novel listericidal STAT-1-mediated signaling pathway that confines multiple innate immune components to the same environment. Second, they show features of MHC class II antigen-loading competent compartments for cathepsin-D-mediated LLO processing. Third, murine cathepsin-D deficiencies fail to develop protective immunity after vaccination with listericidal phago-receptosomes induced by IFN-γ or IL-6. Therefore, it appears that the connection of STAT-1 and cathepsin-D in a single compartment is relevant for protection against listeriosis.

  2. Compartmentation of Metabolism of the C12-, C9-, and C5-n-dicarboxylates in Rat Liver, Investigated by Mass Isotopomer Analysis: ANAPLEROSIS FROM DODECANEDIOATE.

    PubMed

    Jin, Zhicheng; Bian, Fang; Tomcik, Kristyen; Kelleher, Joanne K; Zhang, Guo-Fang; Brunengraber, Henri

    2015-07-24

    We investigated the compartmentation of the catabolism of dodecanedioate (DODA), azelate, and glutarate in perfused rat livers, using a combination of metabolomics and mass isotopomer analyses. Livers were perfused with recirculating or nonrecirculating buffer containing one fully (13)C-labeled dicarboxylate. Information on the peroxisomal versus mitochondrial catabolism was gathered from the labeling patterns of acetyl-CoA proxies, i.e. total acetyl-CoA, the acetyl moiety of citrate, C-1 + 2 of β-hydroxybutyrate, malonyl-CoA, and acetylcarnitine. Additional information was obtained from the labeling patterns of citric acid cycle intermediates and related compounds. The data characterize the partial oxidation of DODA and azelate in peroxisomes, with terminal oxidation in mitochondria. We did not find evidence of peroxisomal oxidation of glutarate. Unexpectedly, DODA contributes a substantial fraction to anaplerosis of the citric acid cycle. This opens the possibility to use water-soluble DODA in nutritional or pharmacological anaplerotic therapy when other anaplerotic substrates are impractical or contraindicated, e.g. in propionic acidemia and methylmalonic acidemia.

  3. Compartmental analysis of (11C)flumazenil kinetics for the estimation of ligand transport rate and receptor distribution using positron emission tomography

    SciTech Connect

    Koeppe, R.A.; Holthoff, V.A.; Frey, K.A.; Kilbourn, M.R.; Kuhl, D.E. )

    1991-09-01

    The in vivo kinetic behavior of (11C)flumazenil ((11C)FMZ), a non-subtype-specific central benzodiazepine antagonist, is characterized using compartmental analysis with the aim of producing an optimized data acquisition protocol and tracer kinetic model configuration for the assessment of (11C)FMZ binding to benzodiazepine receptors (BZRs) in human brain. The approach presented is simple, requiring only a single radioligand injection. Dynamic positron emission tomography data were acquired on 18 normal volunteers using a 60- to 90-min sequence of scans and were analyzed with model configurations that included a three-compartment, four-parameter model, a three-compartment, three-parameter model, with a fixed value for free plus nonspecific binding; and a two-compartment, two-parameter model. Statistical analysis indicated that a four-parameter model did not yield significantly better fits than a three-parameter model. Goodness of fit was improved for three- versus two-parameter configurations in regions with low receptor density, but not in regions with moderate to high receptor density. Thus, a two-compartment, two-parameter configuration was found to adequately describe the kinetic behavior of (11C)FMZ in human brain, with stable estimates of the model parameters obtainable from as little as 20-30 min of data. Pixel-by-pixel analysis yields functional images of transport rate (K1) and ligand distribution volume (DV), and thus provides independent estimates of ligand delivery and BZR binding.

  4. The Early Expression of HLA-DR and CD64 Myeloid Markers Is Specifically Compartmentalized in the Blood and Lungs of Patients with Septic Shock

    PubMed Central

    Mikaszewska-Sokolewicz, Małgorzata; Hoser, Grażyna; Zielińska-Borkowska, Urszula

    2016-01-01

    Identification of reliable biomarkers is key to guide targeted therapies in septic patients. Expression monitoring of monocyte HLA-DR and neutrophil CD64 could fulfill the above need. However, it is unknown whether their expression on circulating cells reflects the status of tissue resident cells. We compared expressions of HLA-DR and CD64 markers in the circulation and airways of septic shock patients and evaluated their outcome prognostic value. The expression of CD64 on neutrophils and HLA-DR on monocytes was analyzed in the peripheral blood and mini-bronchoalveolar lavage fluid cells by flow cytometry. Twenty-seven patients with septic shock were enrolled into the study. The fluorescence intensity of HLA-DR on circulating monocytes was 3.5-fold lower than on the pulmonary monocytes (p = 0.01). The expression of CD64 on circulating and airway neutrophils was similar (p = 0.47). Only the expression of CD64 on circulating neutrophils was higher in nonsurvivors versus survivors (2.8-fold; p = 0.031). Pulmonary monocytes display a higher level of HLA-DR activation compared to peripheral blood monocytes but the expression of neutrophil CD64 is similar on lung and circulating cells. Death in septic patients was effectively predicted by neutrophil CD64 but not monocytic HLA-DR. Prognostic value of cellular activation markers in septic shock appears to strongly depend on their level of compartmentalization. PMID:27413252

  5. Compartmental absorption modeling and site of absorption studies to determine feasibility of an extended-release formulation of an HIV-1 attachment inhibitor phosphate ester prodrug.

    PubMed

    Brown, Jonathan; Chien, Caly; Timmins, Peter; Dennis, Andrew; Doll, Walter; Sandefer, Erik; Page, Richard; Nettles, Richard E; Zhu, Li; Grasela, Dennis

    2013-06-01

    BMS-663068 is a phosphonooxymethyl ester prodrug under development for the treatment of HIV/AIDS. The prodrug is designed to overcome the solubility-limited bioavailability of the active moiety, BMS-626529. BMS-663068 is not absorbed from the gastrointestinal (GI) tract and requires enzymatic conversion by alkaline phosphatase to BMS-626529 immediately before absorption. In the light of the known short in vivo half-life of BMS-626529, compartmental absorption modeling was used to predict the potential feasibility of extended-release (ER) delivery to achieve target Cmax :Cmin ratios. To further refine the model with respect to colonic absorption, the regional absorption of BMS-626529 following delivery of BMS-663068 to upper and lower GI sites was characterized through a site of absorption study in human subjects. A refined model was subsequently applied to guide the development of ER tablet formulations. Comparisons of results from the refined model to the in vivo human pharmacokinetic data for three selected ER formulations demonstrate the utility of the model in predicting feasibility of ER delivery and in directing formulation development.

  6. Transcriptomic Analysis of Streptomyces coelicolor Differentiation in Solid Sporulating Cultures: First Compartmentalized and Second Multinucleated Mycelia Have Different and Distinctive Transcriptomes

    PubMed Central

    Yagüe, Paula; Rodríguez-García, Antonio; López-García, María T.; Martín, Juan F.; Rioseras, Beatriz; Sánchez, Jesús; Manteca, Angel

    2013-01-01

    Streptomycetes are very important industrial bacteria, which produce two thirds of all clinically relevant secondary metabolites. They have a complex developmental-cycle in which an early compartmentalized mycelium (MI) differentiates to a multinucleated mycelium (MII) that grows inside the culture medium (substrate mycelium) until it starts to growth into the air (aerial mycelium) and ends up forming spores. Streptomyces developmental studies have focused mainly on the later stages of MII differentiation (aerial mycelium and sporulation), with regulation of pre-sporulation stages (MI/MII transition) essentially unknown. This work represents the first study of the Streptomyces MI transcriptome, analyzing how it differs from the MII transcriptome. We have used a very conservative experimental approach to fractionate MI from MII and quantify gene expressions. The expression of well characterized key developmental/metabolic genes involved in bioactive compound production (actinorhodin, undecylprodigiosin, calcium-dependent antibiotic, cpk, geosmin) or hydrophobic cover formation-sporulation (bld, whi, wbl, rdl, chp, ram) was correlated with MII differentiation. Additionally, 122 genes conserved in the Streptomyces genus, whose biological function had not been previously characterized, were found to be differentially expressed (more than 4-fold) in MI or MII. These genes encoded for putative regulatory proteins (transcriptional regulators, kinases), as well as hypothetical proteins. Knowledge about differences between the MI (vegetative) and MII (reproductive) transcriptomes represents a huge advance in Streptomyces biology that will make future experiments possible aimed at characterizing the biochemical pathways controlling pre-sporulation developmental stages and activation of secondary metabolism in Streptomyces. PMID:23555999

  7. In vitro digestion of short-dough biscuits enriched in proteins and/or fibres, using a multi-compartmental and dynamic system (1): viscosity measurement and prediction.

    PubMed

    Villemejane, C; Wahl, R; Aymard, P; Denis, S; Michon, C

    2015-09-01

    The effects of biscuit composition on the viscosity generated during digestion were investigated. A control biscuit, one with proteins, one with fibres, and one with both proteins and fibres were digested under the same conditions, using the TNO intestinal model (TIM-1). The TIM-1 is a multi-compartmental and dynamic in vitro system, simulating digestion in the upper tract (stomach and small intestine) of healthy adult humans. Digesta were collected at different times, in the different compartments of the TIM-1 (stomach, duodenum, jejunum and ileum) and viscosity was measured with a dynamic rheometer. Results showed a marked effect of biscuit composition on chyme viscosity. Highest viscosity was obtained with biscuits containing viscous soluble fibres, followed by those enriched in both proteins and fibres, then by protein-enriched and control biscuits. The viscosity was maintained throughout the gut up to the ileal compartment. A prediction of the evolution of the chyme viscosity in each compartment of the TIM-1 was built, based on model curves describing the evolution of the viscosity as a function of biscuit concentration, and on dilution factors measured by spectrophotometry on a blank digestion.

  8. Unique mononuclear Mn(II) complexes of an end-off compartmental Schiff base ligand: experimental and theoretical studies on their bio-relevant catalytic promiscuity.

    PubMed

    Adhikary, Jaydeep; Chakraborty, Aratrika; Dasgupta, Sanchari; Chattopadhyay, Shyamal Kumar; Kruszynski, Rafał; Trzesowska-Kruszynska, Agata; Stepanović, Stepan; Gruden-Pavlović, Maja; Swart, Marcel; Das, Debasis

    2016-08-01

    Three new mononuclear manganese(ii) complexes, namely [Mn(HL)2]·2ClO4 (1), [Mn(HL)(N(CN)2)(H2O)2]·ClO4 (2) and [Mn(HL)(SCN)2] (3) [LH = 4-tert-butyl-2,6-bis-[(2-pyridin-2-yl-ethylimino)-methyl]-phenol], have been synthesized and structurally characterized. An "end-off" compartmental ligand (LH) possesses two symmetrical compartments with N2O binding sites but accommodates only one manganese atom instead of two due to the protonation of the imine nitrogen of one compartment. Although all three complexes are mononuclear, complex 1 is unique as it has a 1 : 2 metal to ligand stoichiometry. The catalytic promiscuity of complexes 1-3 in terms of two different bio-relevant catalytic activities namely catecholase and phenoxazinone synthase has been thoroughly investigated. EPR and cyclic voltametric studies reveal that radical formation rather than metal centered redox participation is responsible for their catecholase-like and phenoxazinone synthase-like catalytic activity. A computational approach suggests that imine bond bound radical generation rather than phenoxo radical formation is most likely responsible for the oxidizing properties of the complexes. PMID:27430642

  9. Compartmentalized and contrasted response of ectomycorrhizal and soil fungal communities of Scots pine forests along elevation gradients in France and Spain.

    PubMed

    Rincón, Ana; Santamaría-Pérez, Blanca; Rabasa, Sonia G; Coince, Aurore; Marçais, Benoit; Buée, Marc

    2015-08-01

    Fungi are principal actors of forest soils implied in many ecosystem services and the mediation of tree's responses. Forecasting fungal responses to environmental changes is necessary for maintaining forest productivity, although our partial understanding of how abiotic and biotic factors affect fungal communities is restricting the predictions. We examined fungal communities of Pinus sylvestris along elevation gradients to check potential responses to climate change-associated factors. Fungi of roots and soils were analysed at a regional scale, by using a high-throughput sequencing approach. Overall soil fungal richness increased with pH, whereas it did not vary with climate. However, when representative sub-assemblages, i.e. Ascomycetes/Basidiomycetes, and families were analysed, they differentially answered to climatic and edaphic variables. This response was dependent on where they settled, i.e. soil versus roots, and/or on their lifestyle, i.e. mycorrhizal or not, suggesting different potential functional weights within the community. Our results revealed a highly compartmentalized and contrasted response of fungal communities in forest soils. The different response of fungal sub-assemblages indicated a range of possible selective direct and indirect (i.e. via host) impacts of climatic variations on these communities, of unknown functional consequences, that helps in understanding potential fungal responses under future global change scenarios. PMID:25953485

  10. Nuclear Data

    SciTech Connect

    White, Morgan C.

    2014-01-23

    PowerPoint presentation targeted for educational use. Nuclear data comes from a variety of sources and in many flavors. Understanding where the data you use comes from and what flavor it is can be essential to understand and interpret your results. This talk will discuss the nuclear data pipeline with particular emphasis on providing links to additional resources that can be used to explore the issues you will encounter.

  11. Nuclear Nonproliferation

    SciTech Connect

    Atkins-Duffin, C E

    2008-12-10

    With an explosion equivalent of about 20kT of TNT, the Trinity test was the first demonstration of a nuclear weapon. Conducted on July 16, 1945 in Alamogordo, NM this site is now a Registered National Historic Landmark. The concept and applicability of nuclear power was demonstrated on December 20, 1951 with the Experimental Breeder Reactor Number One (EBR-1) lit four light bulbs. This reactor is now a Registered National Historic Landmark, located near Arco, ID. From that moment forward it had been clearly demonstrated that nuclear energy has both peaceful and military applications and that the civilian and military fuel cycles can overlap. For the more than fifty years since the Atoms for Peace program, a key objective of nuclear policy has been to enable the wider peaceful use of nuclear energy while preventing the spread of nuclear weapons. Volumes have been written on the impact of these two actions on the world by advocates and critics; pundits and practioners; politicians and technologists. The nations of the world have woven together a delicate balance of treaties, agreements, frameworks and handshakes that are representative of the timeframe in which they were constructed and how they have evolved in time. Collectively these vehicles attempt to keep political will, nuclear materials and technology in check. This paper captures only the briefest abstract of the more significant aspects on the Nonproliferation Regime. Of particular relevance to this discussion is the special nonproliferation sensitivity associated with the uranium isotope separation and spent fuel reprocessing aspects of the nuclear fuel cycle.

  12. Nuclear Structure

    NASA Astrophysics Data System (ADS)

    Gargano, Angela

    2003-04-01

    An account of recent studies in the field of theoretical nuclear structure is reported. These studies concern essentially research activities performed under the Italian project "Fisica Teorica del Nucleo e dei Sistemi a Molti Corpi". Special attention is addressed to results obtained during the last two years as regards the development of new many-body techniques as well as the interpretation of new experimental aspects of nuclear structure.

  13. Nuclear astrophysics

    NASA Astrophysics Data System (ADS)

    Arnould, M.; Takahashi, K.

    1999-03-01

    Nuclear astrophysics is that branch of astrophysics which helps understanding of the Universe, or at least some of its many faces, through the knowledge of the microcosm of the atomic nucleus. It attempts to find as many nuclear physics imprints as possible in the macrocosm, and to decipher what those messages are telling us about the varied constituent objects in the Universe at present and in the past. In the last decades much advance has been made in nuclear astrophysics thanks to the sometimes spectacular progress made in the modelling of the structure and evolution of the stars, in the quality and diversity of the astronomical observations, as well as in the experimental and theoretical understanding of the atomic nucleus and of its spontaneous or induced transformations. Developments in other subfields of physics and chemistry have also contributed to that advance. Notwithstanding the accomplishment, many long-standing problems remain to be solved, and the theoretical understanding of a large variety of observational facts needs to be put on safer grounds. In addition, new questions are continuously emerging, and new facts endangering old ideas. This review shows that astrophysics has been, and still is, highly demanding to nuclear physics in both its experimental and theoretical components. On top of the fact that large varieties of nuclei have to be dealt with, these nuclei are immersed in highly unusual environments which may have a significant impact on their static properties, the diversity of their transmutation modes, and on the probabilities of these modes. In order to have a chance of solving some of the problems nuclear astrophysics is facing, the astrophysicists and nuclear physicists are obviously bound to put their competence in common, and have sometimes to benefit from the help of other fields of physics, like particle physics, plasma physics or solid-state physics. Given the highly varied and complex aspects, we pick here some specific nuclear

  14. Nuclear telemedicine

    NASA Astrophysics Data System (ADS)

    Morrison, R. T.; Szasz, I. J.

    1990-06-01

    Diagnostic nuclear medicine patient images have been transniitted for 8 years from a regional conununity hospital to a university teaching hospital 700 kiloinetres away employing slow scan TV and telephone. Transruission and interpretation were done at the end of each working day or as circumstances required in cases of emergencies. Referring physicians received the nuclear medicine procedure report at the end of the completion day or within few minutes of completion in case of emergency procedures. To date more than 25 patient studies have been transmitted for interpretation. Blinded reinterpretation of the original hard copy data of 350 patient studies resulted in 100 agreement with the interpretation of transmitted data. This technique provides high quality diagnostic and therapeutic nuclear medicine services in remote hospitals where the services of an on-site nuclear physician is not available. 2. HISTORY Eight years ago when the nuclear medicine physician at Trail Regional Hospital left the Trail area and an other could not be recruited we examined the feasibility of image transmission by phone for interpretation since closing the department would have imposed unacceptable physical and financial hardship and medical constraints on the patient population the nearest nuclear medicine facility was at some 8 hours drive away. In hospital patients would have to be treated either based purely on physical findings or flown to Vancouver at considerable cost to the health care system (estimated cost $1500.

  15. SINE (selective inhibitor of nuclear export)--translational science in a new class of anti-cancer agents.

    PubMed

    Gerecitano, John

    2014-10-04

    Regulation of protein trafficking between the nucleus and cytoplasm represents a novel control point for antineoplastic intervention. Several proteins involved with cellular growth and survival depend on precise and timely positioning within the cell to fulfill their functions, and the nuclear membrane defines one of the most important compartmental barriers. Chromosome Region Maintenance 1, or exportin-1 (CRM1/XPO1), is involved with the export of more than 200 nuclear proteins, and has intriguingly been shown to have an increased expression in several tumor cell types. Selinexor (KPT-330) is a first-in-class selective inhibitor of nuclear export (SINE) to be developed for clinical use. Preclinical data has demonstrated antineoplastic activity of SINE compounds in many human solid and hematologic malignancies. The clinical development of Selinexor provides an excellent model for translational research.

  16. Construction of synthetic nucleoli and what it tells us about propagation of sub-nuclear domains through cell division

    PubMed Central

    Grob, Alice; McStay, Brian

    2014-01-01

    The cell nucleus is functionally compartmentalized into numerous membraneless and dynamic, yet defined, bodies. The cell cycle inheritance of these nuclear bodies (NBs) is poorly understood at the molecular level. In higher eukaryotes, their propagation is challenged by cell division through an “open” mitosis, where the nuclear envelope disassembles along with most NBs. A deeper understanding of the mechanisms involved can be achieved using the engineering principles of synthetic biology to construct artificial NBs. Successful biogenesis of such synthetic NBs demonstrates knowledge of the basic mechanisms involved. Application of this approach to the nucleolus, a paradigm of nuclear organization, has highlighted a key role for mitotic bookmarking in the cell cycle propagation of NBs. PMID:25486191

  17. Nuclear waste

    SciTech Connect

    Not Available

    1988-05-01

    This paper discusses how, as part of the Department of Energy's implementation of the Nuclear Waste Policy Act of 1982, DOE is required to investigate a site at Yucca Mountain, Nevada and, if it determines that the site is suitable, recommend to the President its selection for a nuclear waste repository. The Nuclear Regulatory Commission, in considering development of the plan, issued five objections, one of which is DOE's failure to recognize the range of alternative conceptual models of the Yucca Mountain site that can be supported by the limited existing technical data. At the end of the quarter DOE directed its project offices in Washington and Texas to begin orderly phase-out of all site-specific repository activities. Costs for this phase-out are $53 million for the Deaf Smith site and $85 million for the Hanford site.

  18. Nuclear scales

    SciTech Connect

    Friar, J.L.

    1998-12-01

    Nuclear scales are discussed from the nuclear physics viewpoint. The conventional nuclear potential is characterized as a black box that interpolates nucleon-nucleon (NN) data, while being constrained by the best possible theoretical input. The latter consists of the longer-range parts of the NN force (e.g., OPEP, TPEP, the {pi}-{gamma} force), which can be calculated using chiral perturbation theory and gauged using modern phase-shift analyses. The shorter-range parts of the force are effectively parameterized by moments of the interaction that are independent of the details of the force model, in analogy to chiral perturbation theory. Results of GFMC calculations in light nuclei are interpreted in terms of fundamental scales, which are in good agreement with expectations from chiral effective field theories. Problems with spin-orbit-type observables are noted.

  19. Nuclear PI3K signaling in cell growth and tumorigenesis

    PubMed Central

    Davis, William J.; Lehmann, Peter Z.; Li, Weimin

    2015-01-01

    The PI3K/Akt signaling pathway is a major driving force in a variety of cellular functions. Dysregulation of this pathway has been implicated in many human diseases including cancer. While the activity of the cytoplasmic PI3K/Akt pathway has been extensively studied, the functions of these molecules and their effector proteins within the nucleus are poorly understood. Harboring key cellular processes such as DNA replication and repair as well as nascent messenger RNA transcription, the nucleus provides a unique compartmental environment for protein–protein and protein–DNA/RNA interactions required for cell survival, growth, and proliferation. Here we summarize recent advances made toward elucidating the nuclear PI3K/Akt signaling cascade and its key components within the nucleus as they pertain to cell growth and tumorigenesis. This review covers the spatial and temporal localization of the major nuclear kinases having PI3K activities and the counteracting phosphatases as well as the role of nuclear PI3K/Akt signaling in mRNA processing and exportation, DNA replication and repair, ribosome biogenesis, cell survival, and tumorigenesis. PMID:25918701

  20. Nuclear pursuits

    SciTech Connect

    Not Available

    1993-05-01

    This table lists quantities of warheads (in stockpile, peak number per year, total number built, number of known test explosions), weapon development milestones (developers of the atomic bomb and hydrogen bomb, date of first operational ICBM, first nuclear-powered naval SSN in service, first MIRVed missile deployed), and testing milestones (first fission test, type of boosted fission weapon, multistage thermonuclear test, number of months from fission bomb to multistage thermonuclear bomb, etc.), and nuclear infrastructure (assembly plants, plutonium production reactors, uranium enrichment plants, etc.). Countries included in the tally are the United States, Soviet Union, Britain, France, and China.

  1. Nuclear power: Fourth edition

    SciTech Connect

    Deutsch, R.W.

    1986-01-01

    This book describes the basics of nuclear power generation, explaining both the benefits and the real and imagined risks of nuclear power. It includes a discussion of the Three Mile Island accident and its effects. Nuclear Power has been used in the public information programs of more than 100 utilities. The contents discussed are: Nuclear Power and People; Why Nuclear Power. Electricity produced by coal; Electricity produced by nuclear fuel; Nuclear plant sites in the United States; Short History of Commercial Nuclear Power; U.S. nuclear submarines, Regulation of Nuclear Power Plants; Licensing process, Nuclear Power Plant Operator Training; Nuclear power plant simulator, Are Nuclear Plants Safe.; Containment structure, Nuclear Power Plant Insurance; Is Radiation Dangerous.; Man-made radiation, What is Nuclear Fuel.; Fuel cycle for commercial nuclear power plants; Warm Water Discharge; Cooling tower; Protection of Radioactive Materials; Plutonium and Proliferation; Disposal of Radioactive Wastes; Are Alternate Energy Sources Available.; Nuclear Opposition; and Nuclear Power in the Future.

  2. Scanning electrochemical microscopy at the surface of bone-resorbing osteoclasts: evidence for steady-state disposal and intracellular functional compartmentalization of calcium.

    PubMed

    Berger, C E; Rathod, H; Gillespie, J I; Horrocks, B R; Datta, H K

    2001-11-01

    +]e. We found that an increase in [Ca2+]i may be associated with activation; inhibition; or be without effect on O2.- generation, bone-matrix, or bone resorption. Similarly, osteoclast adhesion and bone-resorbing activity was affected by [Ca2+]e' but showed no correlation with [Ca2+]i. The data suggest the existence of functional compartmentalization of [Ca2+]i within the osteoclast, where elevated calcium may have an inhibitory, excitatory, or no effect on the overall osteoclast activity while exerting a selective effect on different functional modalities. These observations lead to the conclusion that far from being inhibited by Ca2+ generated, the osteoclast by virtue of the observed functional compartmentalization is highly adapted at carrying out its activity even when the level of [Ca2+] in resorptive lacunae is elevated.

  3. Androgen receptor regulates nuclear trafficking and nuclear domain residency of corepressor HDAC7 in a ligand-dependent fashion

    SciTech Connect

    Karvonen, Ulla; Jaenne, Olli A.; Palvimo, Jorma J. . E-mail: jorma.palvimo@uku.fi

    2006-10-01

    In addition to chromosomal proteins, histone deacetylases (HDACs) target transcription factors in transcriptional repression. Here, we show that the class II HDAC family member HDAC7 is an efficient corepressor of the androgen receptor (AR). HDAC7 resided in the cytoplasm in the absence of AR or a cognate ligand, but hormone-occupancy of AR induced nuclear transfer of HDAC7. Nuclear colocalization pattern of AR and HDAC7 was dependent on the nature of the ligand. In the presence of testosterone, a portion of HDAC7 localized to pearl-like nuclear domains, whereas AR occupied with antagonistic ligands cyproterone acetate- or casodex (bicalutamide) recruited HDAC7 from these domains to colocalize with the receptor in speckles and nucleoplasm in a more complete fashion. Ectopic expression of PML-3 relieved the repressive effect of HDAC7 on AR function by sequestering HDAC7 to PML-3 domains. AR acetylation at Lys630/632/633 was not the target of HDAC7 repression, since repression of AR function was independent of these acetylation sites. Moreover, the deacetylase activity of HDAC7 was in part dispensable in the repression of AR function. In sum, our results identify HDAC7 as a novel AR corepressor whose subcellular and subnuclear compartmentalization can be regulated in an androgen-selective manner.

  4. High-resolution analysis of gut environment and bacterial microbiota reveals functional compartmentation of the gut in wood-feeding higher termites (Nasutitermes spp.).

    PubMed

    Köhler, Tim; Dietrich, Carsten; Scheffrahn, Rudolf H; Brune, Andreas

    2012-07-01

    Higher termites are characterized by a purely prokaryotic gut microbiota and an increased compartmentation of their intestinal tract. In soil-feeding species, each gut compartment has different physicochemical conditions and is colonized by a specific microbial community. Although considerable information has accumulated also for wood-feeding species of the genus Nasutitermes, including cellulase activities and metagenomic data, a comprehensive study linking physicochemical gut conditions with the structure of the microbial communities in the different gut compartments is lacking. In this study, we measured high-resolution profiles of H(2), O(2), pH, and redox potential in the gut of Nasutitermes corniger termites, determined the fermentation products accumulating in the individual gut compartments, and analyzed the bacterial communities in detail by pyrotag sequencing of the V3-V4 region of the 16S rRNA genes. The dilated hindgut paunch (P3 compartment) was the only anoxic gut region, showed the highest density of bacteria, and accumulated H(2) to high partial pressures (up to 12 kPa). Molecular hydrogen is apparently produced by a dense community of Spirochaetes and Fibrobacteres, which also dominate the gut of other Nasutitermes species. All other compartments, such as the alkaline P1 compartment (average pH, 10.0), showed high redox potentials and comprised small but distinct populations characteristic for each gut region. In the crop and the posterior hindgut compartments, the community was even more diverse than in the paunch. Similarities in the communities of the posterior hindgut and crop suggested that proctodeal trophallaxis or coprophagy also occurs in higher termites. The large sampling depths of pyrotag sequencing in combination with the determination of important physicochemical parameters allow cautious conclusions concerning the functions of particular bacterial lineages in the respective gut sections to be drawn. PMID:22544239

  5. A Compartmental Comparison of Major Lipid Species in a Coral-Symbiodinium Endosymbiosis: Evidence that the Coral Host Regulates Lipogenesis of Its Cytosolic Lipid Bodies

    PubMed Central

    Chen, Hung-Kai; Song, Shin-Ni; Wang, Li-Hsueh; Mayfield, Anderson B.; Chen, Yi-Jyun; Chen, Wan-Nan U.; Chen, Chii-Shiarng

    2015-01-01

    The lipid body (LB) formation in the host coral gastrodermal cell cytoplasm is a hallmark of the coral-Symbiodinium endosymbiosis, and such lipid-based entities are not found in endosymbiont-free cnidarian cells. Therefore, the elucidation of lipogenesis regulation in LBs and how it is related to the lipid metabolism of the host and endosymbiont could provide direct insight to understand the symbiosis mechanism. Herein, the lipid composition of host cells of the stony coral Euphyllia glabrescens, as well as that of their cytoplasmic LBs and in hospite Symbiodinium populations, was examined by high performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS), and six major lipid species were identified: wax esters, sterol esters, triacylglycerols, cholesterols, free fatty acids, and phospholipids. Their concentrations differed significantly between host coral cells, LBs, and Symbiodinium, suggesting compartmental regulation. WE were only present in the host coral and were particularly highly concentrated in LBs. Amongst the four species of WE, the monoene R = C18:1/R = C16 was found to be LB-specific and was not present in the host gastrodermal cell cytoplasm. Furthermore, the acyl pool profiles of the individual LB lipid species were more similar, but not equal to, those of the host gastrodermal cells in which they were located, indicating partially autonomous lipid metabolism in these LBs. Nevertheless, given the overall similarity in the host gastrodermal cell and LB lipid profiles, these data suggest that a significant portion of the LB lipids may be of host coral origin. Finally, lipid profiles of the in hospite Symbiodinium populations were significantly distinct from those of the cultured Symbiodinium, potentially suggesting a host regulation effect that may be fundamental to lipid metabolism in endosymbiotic associations involving clade C Symbiodinium. PMID:26218797

  6. High-Resolution Analysis of Gut Environment and Bacterial Microbiota Reveals Functional Compartmentation of the Gut in Wood-Feeding Higher Termites (Nasutitermes spp.)

    PubMed Central

    Köhler, Tim; Dietrich, Carsten; Scheffrahn, Rudolf H.

    2012-01-01

    Higher termites are characterized by a purely prokaryotic gut microbiota and an increased compartmentation of their intestinal tract. In soil-feeding species, each gut compartment has different physicochemical conditions and is colonized by a specific microbial community. Although considerable information has accumulated also for wood-feeding species of the genus Nasutitermes, including cellulase activities and metagenomic data, a comprehensive study linking physicochemical gut conditions with the structure of the microbial communities in the different gut compartments is lacking. In this study, we measured high-resolution profiles of H2, O2, pH, and redox potential in the gut of Nasutitermes corniger termites, determined the fermentation products accumulating in the individual gut compartments, and analyzed the bacterial communities in detail by pyrotag sequencing of the V3-V4 region of the 16S rRNA genes. The dilated hindgut paunch (P3 compartment) was the only anoxic gut region, showed the highest density of bacteria, and accumulated H2 to high partial pressures (up to 12 kPa). Molecular hydrogen is apparently produced by a dense community of Spirochaetes and Fibrobacteres, which also dominate the gut of other Nasutitermes species. All other compartments, such as the alkaline P1 compartment (average pH, 10.0), showed high redox potentials and comprised small but distinct populations characteristic for each gut region. In the crop and the posterior hindgut compartments, the community was even more diverse than in the paunch. Similarities in the communities of the posterior hindgut and crop suggested that proctodeal trophallaxis or coprophagy also occurs in higher termites. The large sampling depths of pyrotag sequencing in combination with the determination of important physicochemical parameters allow cautious conclusions concerning the functions of particular bacterial lineages in the respective gut sections to be drawn. PMID:22544239

  7. Resolving the Compartmentation and Function of C4 Photosynthesis in the Single-Cell C4 Species Bienertia sinuspersici1[OA

    PubMed Central

    Offermann, Sascha; Okita, Thomas W.; Edwards, Gerald E.

    2011-01-01

    Bienertia sinuspersici is a land plant known to perform C4 photosynthesis through the location of dimorphic chloroplasts in separate cytoplasmic domains within a single photosynthetic cell. A protocol was developed with isolated protoplasts to obtain peripheral chloroplasts (P-CP), a central compartment (CC), and chloroplasts from the CC (C-CP) to study the subcellular localization of photosynthetic functions. Analyses of these preparations established intracellular compartmentation of processes to support a NAD-malic enzyme (ME)-type C4 cycle. Western-blot analyses indicated that the CC has Rubisco from the C3 cycle, the C4 decarboxylase NAD-ME, a mitochondrial isoform of aspartate aminotransferase, and photorespiratory markers, while the C-CP and P-CP have high levels of Rubisco and pyruvate, Pidikinase, respectively. Other enzymes for supporting a NAD-ME cycle via an aspartate-alanine shuttle, carbonic anhydrase, phosophoenolpyruvate carboxylase, alanine, and an isoform of aspartate aminotransferase are localized in the cytosol. Functional characterization by photosynthetic oxygen evolution revealed that only the C-CP have a fully operational C3 cycle, while both chloroplast types have the capacity to photoreduce 3-phosphoglycerate. The P-CP were enriched in a putative pyruvate transporter and showed light-dependent conversion of pyruvate to phosphoenolpyruvate. There is a larger investment in chloroplasts in the central domain than in the peripheral domain (6-fold more chloroplasts and 4-fold more chlorophyll). The implications of this uneven distribution for the energetics of the C4 and C3 cycles are discussed. The results indicate that peripheral and central compartment chloroplasts in the single-cell C4 species B. sinuspersici function analogous to mesophyll and bundle sheath chloroplasts of Kranz-type C4 species. PMID:21263039

  8. Evaluating the degradation of the herbicides picloram and 2,4-D in a compartmentalized reactive biobarrier with internal liquid recirculation.

    PubMed

    Ordaz-Guillén, Yolanda; Galíndez-Mayer, Cutberto Juvencio; Ruiz-Ordaz, Nora; Juárez-Ramírez, Cleotilde; Santoyo-Tepole, Fortunata; Ramos-Monroy, Oswaldo

    2014-01-01

    Tordon is a widely used herbicide formulation of 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-amino-3,5,6-trichloropicolinic acid (picloram), and it is considered a toxic herbicide. The purposes of this work were to assess the feasibility of a microbial consortium inoculated in a lab-scale compartmentalized biobarrier, to remove these herbicides, and isolate, identify, and evaluate their predominant microbial constituents. Volumetric loading rates of herbicides ranging from 31.2 to 143.9 g m(-3) day(-1), for 2,4-D, and 12.8 to 59.3 g m(-3) day(-1) for picloram were probed; however, the top operational limit of the biobarrier, detected by a decay in the removal efficiency, was not reached. At the highest loading rates probed, high average removal efficiencies of 2,4-D, 99.56 ± 0.44; picloram, 94.58 ± 2.62; and chemical oxygen demand (COD), 89.42 ± 3.68, were obtained. It was found that the lab-scale biofilm reactor efficiently removed both herbicides at dilution rates ranging from 0.92 to 4.23 day(-1), corresponding to hydraulic retention times from 1.087 to 0.236 days. On the other hand, few microbial strains able to degrade picloram are reported in the literature. In this work, three of the nine bacterial strains isolated cometabolically degrade picloram. They were identified as Hydrocarboniphaga sp., Tsukamurella sp., and Cupriavidus sp.

  9. A Compartmental Comparison of Major Lipid Species in a Coral-Symbiodinium Endosymbiosis: Evidence that the Coral Host Regulates Lipogenesis of Its Cytosolic Lipid Bodies.

    PubMed

    Chen, Hung-Kai; Song, Shin-Ni; Wang, Li-Hsueh; Mayfield, Anderson B; Chen, Yi-Jyun; Chen, Wan-Nan U; Chen, Chii-Shiarng

    2015-01-01

    The lipid body (LB) formation in the host coral gastrodermal cell cytoplasm is a hallmark of the coral-Symbiodinium endosymbiosis, and such lipid-based entities are not found in endosymbiont-free cnidarian cells. Therefore, the elucidation of lipogenesis regulation in LBs and how it is related to the lipid metabolism of the host and endosymbiont could provide direct insight to understand the symbiosis mechanism. Herein, the lipid composition of host cells of the stony coral Euphyllia glabrescens, as well as that of their cytoplasmic LBs and in hospite Symbiodinium populations, was examined by high performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS), and six major lipid species were identified: wax esters, sterol esters, triacylglycerols, cholesterols, free fatty acids, and phospholipids. Their concentrations differed significantly between host coral cells, LBs, and Symbiodinium, suggesting compartmental regulation. WE were only present in the host coral and were particularly highly concentrated in LBs. Amongst the four species of WE, the monoene R = C18:1/R = C16 was found to be LB-specific and was not present in the host gastrodermal cell cytoplasm. Furthermore, the acyl pool profiles of the individual LB lipid species were more similar, but not equal to, those of the host gastrodermal cells in which they were located, indicating partially autonomous lipid metabolism in these LBs. Nevertheless, given the overall similarity in the host gastrodermal cell and LB lipid profiles, these data suggest that a significant portion of the LB lipids may be of host coral origin. Finally, lipid profiles of the in hospite Symbiodinium populations were significantly distinct from those of the cultured Symbiodinium, potentially suggesting a host regulation effect that may be fundamental to lipid metabolism in endosymbiotic associations involving clade C Symbiodinium. PMID:26218797

  10. Nuclear Membrane Dynamics and Reassembly in Living Cells: Targeting of an Inner Nuclear Membrane Protein in Interphase and Mitosis

    PubMed Central

    Ellenberg, Jan; Siggia, Eric D.; Moreira, Jorge E.; Smith, Carolyn L.; Presley, John F.; Worman, Howard J.; Lippincott-Schwartz, Jennifer

    1997-01-01

    The mechanisms of localization and retention of membrane proteins in the inner nuclear membrane and the fate of this membrane system during mitosis were studied in living cells using the inner nuclear membrane protein, lamin B receptor, fused to green fluorescent protein (LBR–GFP). Photobleaching techniques revealed the majority of LBR–GFP to be completely immobilized in the nuclear envelope (NE) of interphase cells, suggesting a tight binding to heterochromatin and/or lamins. A subpopulation of LBR–GFP within ER membranes, by contrast, was entirely mobile and diffused rapidly and freely (D = 0.41 ± 0.1 μm2/s). High resolution confocal time-lapse imaging in mitotic cells revealed LBR–GFP redistributing into the interconnected ER membrane system in prometaphase, exhibiting the same high mobility and diffusion constant as observed in interphase ER membranes. LBR–GFP rapidly diffused across the cell within the membrane network defined by the ER, suggesting the integrity of the ER was maintained in mitosis, with little or no fragmentation and vesiculation. At the end of mitosis, nuclear membrane reformation coincided with immobilization of LBR–GFP in ER elements at contact sites with chromatin. LBR–GFP–containing ER membranes then wrapped around chromatin over the course of 2–3 min, quickly and efficiently compartmentalizing nuclear material. Expansion of the NE followed over the course of 30–80 min. Thus, selective changes in lateral mobility of LBR–GFP within the ER/NE membrane system form the basis for its localization to the inner nuclear membrane during interphase. Such changes, rather than vesiculation mechanisms, also underlie the redistribution of this molecule during NE disassembly and reformation in mitosis. PMID:9298976

  11. Nuclear medicine

    SciTech Connect

    Wagner, H.N. Jr.

    1986-10-17

    In 1985 and 1986 nuclear medicine became more and more oriented toward in vov chemistry, chiefly as a result of advances in positron emission tomography (PET). The most important trend was the extension of PET technology into the care of patients with brain tumors, epilepsy, and heart disease. A second trend was the increasing use of single-photon emission computed tomography (SPECT).

  12. NUCLEAR REACTOR

    DOEpatents

    Treshow, M.

    1961-09-01

    A boiling-water nuclear reactor is described wherein control is effected by varying the moderator-to-fuel ratio in the reactor core. This is accomplished by providing control tubes containing a liquid control moderator in the reactor core and providing means for varying the amount of control moderatcr within the control tubes.

  13. Nuclear Science.

    ERIC Educational Resources Information Center

    Pennsylvania State Dept. of Education, Harrisburg. Bureau of Curriculum Services.

    This document is a report on a course in nuclear science for the high school curriculum. The course is designed to provide a basic but comprehensive understanding of the atom in the light of modern knowledge, and to show how people attempt to harness the tremendous energy liberated through fission and fusion reactions. The course crosses what are…

  14. Nuclear Misinformation

    ERIC Educational Resources Information Center

    Ford, Daniel F.; Kendall, Henry W.

    1975-01-01

    Many scientists feel that research into nuclear safety has been diverted or distorted, and the results of the research concealed or inaccurately reported on a large number of occasions. Of particular concern have been the emergency cooling systems which have not, as yet, been adequately tested. (Author/MA)

  15. Nuclear explosions

    SciTech Connect

    Broyles, A.A.

    1982-07-01

    A summary of the physics of a nuclear bomb explosion and its effects on human beings is presented at the level of a sophomore general physics course without calculus. It is designed to supplement a standard text for such a course and problems are included.

  16. Nuclear energy.

    PubMed

    Wilson, Peter D

    2010-01-01

    The technical principles and practices of the civil nuclear industry are described with particular reference to fission and its products, natural and artificial radioactivity elements principally concerned and their relationships, main types of reactor, safety issues, the fuel cycle, waste management, issues related to weapon proliferation, environmental considerations and possible future developments.

  17. Nuclear Terrorism.

    SciTech Connect

    Hecker, Siegfried S.

    2001-01-01

    As pointed out by several speakers, the level of violence and destruction in terrorist attacks has increased significantly during the past decade. Fortunately, few have involved weapons of mass destruction, and none have achieved mass casualties. The Aum Shinrikyo release of lethal nerve agent, sarin, in the Tokyo subway on March 20, 1995 clearly broke new ground by crossing the threshold in attempting mass casualties with chemical weapons. However, of all weapons of mass destruction, nuclear weapons still represent the most frightening threat to humankind. Nuclear weapons possess an enormous destructive force. The immediacy and scale of destruction are unmatched. In addition to destruction, terrorism also aims to create fear among the public and governments. Here also, nuclear weapons are unmatched. The public's fear of nuclear weapons or, for that matter, of all radioactivity is intense. To some extent, this fear arises from a sense of unlimited vulnerability. That is, radioactivity is seen as unbounded in three dimensions - distance, it is viewed as having unlimited reach; quantity, it is viewed as having deadly consequences in the smallest doses (the public is often told - incorrectly, of course - that one atom of plutonium will kill); and time, if it does not kill you immediately, then it will cause cancer decades hence.

  18. Sensitivity Analysis Predicts that the ERK-pMEK Interaction Regulates ERK Nuclear Translocation

    PubMed Central

    Radhakrishnan, Krishnan; Edwards, Jeremy S; Lidke, Diane S; Jovin, Thomas M; Wilson, Bridget S; Oliver, Janet M

    2011-01-01

    Following phosphorylation, nuclear translocation of the mitogen-activated protein kinases (MAPKs), ERK1 and ERK2, is critical for both gene expression and DNA replication induced by growth factors. ERK nuclear translocation has therefore been studied extensively, but many details remain unresolved, including whether or not ERK dimerization is required for translocation. Here, we simulate ERK nuclear translocation with a compartmental computational model that includes systematic sensitivity analysis. The governing ordinary differential equations are solved with the backward differentiation formula and decoupled direct methods. To better understand the regulation of ERK nuclear translocation, we use this model in conjunction with a previously published model of the ERK pathway that does not include an ERK dimer species and with experimental measurements of nuclear translocation of wild-type ERK and a mutant form, ERK1-Δ4, which is unable to dimerize. Sensitivity analysis reveals that the delayed nuclear uptake of ERK1-Δ4 compared to that of wild-type ERK1 can be explained by the altered interaction of ERK1-Δ4 with phosphorylated MEK (MAPK/ERK kinase), and so may be independent of dimerization. Our study also identifies biological experiments that can verify this explanation. PMID:21028924

  19. Granulocytic nuclear differentiation of lamin B receptor-deficient mouse EPRO cells

    PubMed Central

    Zwerger, Monika; Herrmann, Harald; Gaines, Peter; Olins, Ada L.; Olins, Donald E.

    2008-01-01

    Objective Lamin B receptor (LBR) is an integral protein of the inner nuclear membrane. Recent studies have demonstrated that genetic deficiency of LBR during granulopoiesis results in hypolobulation of the mature neutrophil nucleus, as observed in human Pelger-Huët anomaly (PHA) and mouse ichthyosis (ic). In this study we have utilized differentiated promyelocytes (EPRO cells) that were derived from the bone marrow of homozygous and heterozygous ichthyosis mice to examine changes to the expression of nuclear envelope proteins and heterochromatin structure that result from deficient LBR expression. Materials and Methods Wildtype (+/+), heterozygous (+/ic) and homozygous (ic/ic) granulocytic forms of EPRO cells were analyzed for the expression of multiple lamins and inner nuclear envelope proteins by immunostaining and immunoblotting techniques. The heterochromatin architecture was also examined by immunostaining for histone lysine methylation. Results Wildtype (+/+) and heterozygous (+/ic) granulocytic forms revealed ring-shaped nuclei and contained LBR within the nuclear envelope; ic/ic granulocytes exhibited smaller ovoid nuclei devoid of LBR. The pericentric heterochromatin of undifferentiated and granulocytic ic/ic cells was condensed into larger spots and shifted away from the nuclear envelope, compared to +/+ and +/ic cell forms. Lamin A/C, which is normally not present in mature granulocytes, was significantly elevated in LBR-deficient EPRO cells. Conclusions Our observations suggest roles for LBR during granulopoiesis which may involve augmenting nuclear membrane growth, facilitating compartmentalization of heterochromatin and promoting down-regulation of lamin A/C expression. PMID:18495328

  20. Nuclear politics

    NASA Astrophysics Data System (ADS)

    Ranson, John

    2009-04-01

    The sentiments expressed by Sidney Drell in his forum article "The nuclear threat: a new start" (February pp16-17) are laudable, but it was disappointing to find this almost entirely political story in isolation. The article, which outlined the prospects for reducing weapons stockpiles under the new US administration, would have been more pertinent as an introduction to a series describing the technology used in detecting nuclear-testing activity. It would have been interesting to discuss the specific equipment and methods used, together with the analysis and correlation techniques - along with an indication of how sensitive and reliable they are (if the information is not classified). It is far easier to detect an explosive event than it is to detect and quantify weapons stores, which is a key factor for any negotiated solution. Apart from deductions based on actual inspection and satellite surveillance, are there other techniques that can be applied to this issue?

  1. NUCLEAR REACTORS

    DOEpatents

    Long, E.; Ashby, J.W.

    1958-09-16

    ABS>A graphite moderator structure is presented for a nuclear reactor compriscd of an assembly of similarly orientated prismatic graphite blocks arranged on spaced longitudinal axes lying in common planes wherein the planes of the walls of the blocks are positioned so as to be twisted reintive to the planes of said axes so thatthe unlmpeded dtrect paths in direction wholly across the walls of the blocks are limited to the width of the blocks plus spacing between the blocks.

  2. NUCLEAR REACTOR

    DOEpatents

    Anderson, C.R.

    1962-07-24

    A fluidized bed nuclear reactor and a method of operating such a reactor are described. In the design means are provided for flowing a liquid moderator upwardly through the center of a bed of pellets of a nentron-fissionable material at such a rate as to obtain particulate fluidization while constraining the lower pontion of the bed into a conical shape. A smooth circulation of particles rising in the center and falling at the outside of the bed is thereby established. (AEC)

  3. Nuclear Chirality

    SciTech Connect

    Starosta, Krzysztof

    2005-04-05

    Nuclear chirality is a novel manifestation of spontaneous symmetry breaking resulting from an orthogonal coupling of angular momentum vectors in triaxial nuclei. Three perpendicular angular momenta can form two systems of opposite handedness; the time reversal operator, which reverses orientation of each of the angular momentum components, relates these two systems. The status of current experimental searches for chiral doubling of states, as well as recent progress on the theoretical side is reviewed.

  4. Nuclear waste

    SciTech Connect

    Not Available

    1991-09-01

    Radioactive waste is mounting at U.S. nuclear power plants at a rate of more than 2,000 metric tons a year. Pursuant to statute and anticipating that a geologic repository would be available in 1998, the Department of Energy (DOE) entered into disposal contracts with nuclear utilities. Now, however, DOE does not expect the repository to be ready before 2010. For this reason, DOE does not want to develop a facility for monitored retrievable storage (MRS) by 1998. This book is concerned about how best to store the waste until a repository is available, congressional requesters asked GAO to review the alternatives of continued storage at utilities' reactor sites or transferring waste to an MRS facility, GAO assessed the likelihood of an MRSA facility operating by 1998, legal implications if DOE is not able to take delivery of wastes in 1998, propriety of using the Nuclear Waste Fund-from which DOE's waste program costs are paid-to pay utilities for on-site storage capacity added after 1998, ability of utilities to store their waste on-site until a repository is operating, and relative costs and safety of the two storage alternatives.

  5. Nuclear terrorism.

    PubMed

    Hogan, David E; Kellison, Ted

    2002-06-01

    Recent events have heightened awareness of the potential for terrorist attacks employing nonconventional weaponry such as biological agents and radiation. Historically, the philosophy of nuclear risk has focused on global or strategic nuclear exchanges and the resulting damage from large-scale releases. Currently, nuclear accidents or terrorist attacks involving low-level or regional release of radiation are considered the most likely events. Thus far, there have been several regional radiation incidents exposing hundreds of thousands of people to radiation, but there have been only a limited number of significant contaminations resulting in death. There are several different types of radioactive particles that differ in mass, extent of radiation emitted, and the degree to which tissue penetration occurs. Radiation affects its toxicity on biological systems by ionization, which creates tissue damage by the generation of free radicals, disruption of chemical bonds, and directly damaging cellular DNA and enzymes. The extent of damage depends on the type of radioisotope and the radiation dose. Radiation doses exceeding 2 to 10 Gy are considered lethal. Optimal management of radiation casualties requires knowledge of the type and dose of radiation received, a recognition of the manifestations of radiation sickness, and the use of standard medical care, decontamination, and decorporation techniques. PMID:12074488

  6. NUCLEAR REACTOR

    DOEpatents

    Grebe, J.J.

    1959-07-14

    High temperature reactors which are uniquely adapted to serve as the heat source for nuclear pcwered rockets are described. The reactor is comprised essentially of an outer tubular heat resistant casing which provides the main coolant passageway to and away from the reactor core within the casing and in which the working fluid is preferably hydrogen or helium gas which is permitted to vaporize from a liquid storage tank. The reactor core has a generally spherical shape formed entirely of an active material comprised of fissile material and a moderator material which serves as a diluent. The active material is fabricated as a gas permeable porous material and is interlaced in a random manner with very small inter-connecting bores or capillary tubes through which the coolant gas may flow. The entire reactor is divided into successive sections along the direction of the temperature gradient or coolant flow, each section utilizing materials of construction which are most advantageous from a nuclear standpoint and which at the same time can withstand the operating temperature of that particular zone. This design results in a nuclear reactor characterized simultaneously by a minimum critiral size and mass and by the ability to heat a working fluid to an extremely high temperature.

  7. Nuclear photonics

    SciTech Connect

    Habs, D.; Guenther, M. M.; Jentschel, M.; Thirolf, P. G.

    2012-07-09

    With the planned new {gamma}-beam facilities like MEGa-ray at LLNL (USA) or ELI-NP at Bucharest (Romania) with 10{sup 13}{gamma}/s and a band width of {Delta}E{gamma}/E{gamma} Almost-Equal-To 10{sup -3}, a new era of {gamma} beams with energies up to 20MeV comes into operation, compared to the present world-leading HI{gamma}S facility at Duke University (USA) with 10{sup 8}{gamma}/s and {Delta}E{gamma}/E{gamma} Almost-Equal-To 3 Dot-Operator 10{sup -2}. In the long run even a seeded quantum FEL for {gamma} beams may become possible, with much higher brilliance and spectral flux. At the same time new exciting possibilities open up for focused {gamma} beams. Here we describe a new experiment at the {gamma} beam of the ILL reactor (Grenoble, France), where we observed for the first time that the index of refraction for {gamma} beams is determined by virtual pair creation. Using a combination of refractive and reflective optics, efficient monochromators for {gamma} beams are being developed. Thus, we have to optimize the total system: the {gamma}-beam facility, the {gamma}-beam optics and {gamma} detectors. We can trade {gamma} intensity for band width, going down to {Delta}E{gamma}/E{gamma} Almost-Equal-To 10{sup -6} and address individual nuclear levels. The term 'nuclear photonics' stresses the importance of nuclear applications. We can address with {gamma}-beams individual nuclear isotopes and not just elements like with X-ray beams. Compared to X rays, {gamma} beams can penetrate much deeper into big samples like radioactive waste barrels, motors or batteries. We can perform tomography and microscopy studies by focusing down to {mu}m resolution using Nuclear Resonance Fluorescence (NRF) for detection with eV resolution and high spatial resolution at the same time. We discuss the dominating M1 and E1 excitations like the scissors mode, two-phonon quadrupole octupole excitations, pygmy dipole excitations or giant dipole excitations under the new facet of

  8. Nuclear photonics

    NASA Astrophysics Data System (ADS)

    Habs, D.; Günther, M. M.; Jentschel, M.; Thirolf, P. G.

    2012-07-01

    With the planned new γ-beam facilities like MEGa-ray at LLNL (USA) or ELI-NP at Bucharest (Romania) with 1013 γ/s and a band width of ΔEγ/Eγ≈10-3, a new era of γ beams with energies up to 20MeV comes into operation, compared to the present world-leading HIγS facility at Duke University (USA) with 108 γ/s and ΔEγ/Eγ≈3ṡ10-2. In the long run even a seeded quantum FEL for γ beams may become possible, with much higher brilliance and spectral flux. At the same time new exciting possibilities open up for focused γ beams. Here we describe a new experiment at the γ beam of the ILL reactor (Grenoble, France), where we observed for the first time that the index of refraction for γ beams is determined by virtual pair creation. Using a combination of refractive and reflective optics, efficient monochromators for γ beams are being developed. Thus, we have to optimize the total system: the γ-beam facility, the γ-beam optics and γ detectors. We can trade γ intensity for band width, going down to ΔEγ/Eγ≈10-6 and address individual nuclear levels. The term "nuclear photonics" stresses the importance of nuclear applications. We can address with γ-beams individual nuclear isotopes and not just elements like with X-ray beams. Compared to X rays, γ beams can penetrate much deeper into big samples like radioactive waste barrels, motors or batteries. We can perform tomography and microscopy studies by focusing down to μm resolution using Nuclear Resonance Fluorescence (NRF) for detection with eV resolution and high spatial resolution at the same time. We discuss the dominating M1 and E1 excitations like the scissors mode, two-phonon quadrupole octupole excitations, pygmy dipole excitations or giant dipole excitations under the new facet of applications. We find many new applications in biomedicine, green energy, radioactive waste management or homeland security. Also more brilliant secondary beams of neutrons and positrons can be produced.

  9. Cellular compartmentalization of secondary metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors sh...

  10. Compartmentalization of bacteria in microcapsules.

    PubMed

    van Wijk, Judith; Heunis, Tiaan; Harmzen, Elrika; Dicks, Leon M T; Meuldijk, Jan; Klumperman, Bert

    2014-12-18

    Lactobacillus plantarum strain 423 was encapsulated in hollow poly(organosiloxane) microcapsules by templating water-in-oil Pickering emulsion droplets via the interfacial reaction of alkylchlorosilanes. The bacteria were suspended in growth medium or buffer to protect the cells against pH changes during the interfacial reactions with alkylchlorosilanes. The results of this work open up novel avenues for the encapsulation of microbial cells.

  11. Plasma Retinol Kinetics and β-Carotene Bioefficacy Are Quantified by Model-Based Compartmental Analysis in Healthy Young Adults with Low Vitamin A Stores12

    PubMed Central

    Green, Michael H; Ford, Jennifer Lynn; Oxley, Anthony; Green, Joanne Balmer; Park, Hyunjin; Berry, Philip; Boddy, Alan V; Lietz, Georg

    2016-01-01

    Background: Model-based compartmental analysis of data on plasma retinol kinetics after administration of labeled retinol provides unique information about whole-body vitamin A metabolism. If labeled β-carotene is coadministered, its bioefficacy relative to the retinol reference dose can also be estimated. Objectives: The objectives were to model plasma retinol kinetics after administration of labeled preformed vitamin A and provitamin A β-carotene and to determine relative β-carotene bioefficacy. Methods: We used the Simulation, Analysis and Modeling software (WinSAAM version 3.0.8; http://www.WinSAAM.org) to analyze previously collected data on plasma [13C10]- and [13C5]retinol kinetics for 14 d after oral administration of 1 mg [13C10]retinyl acetate and 2 mg [13C10]β-carotene in oil to 30 healthy young adults of European ancestry [13 men, 17 women; mean ± SD age: 24.5 ± 4.2 y; mean ± SD body weight: 65.2 ± 10 kg; mean ± SD body mass index (in kg/m2): 22.5 ± 1.9] with moderate vitamin A intakes. Results: A 6-component model provided the best fit to the data, including compartments for initial metabolism of vitamin A, plasma retinol, and extravascular vitamin A storage. The disposal rate was 6.7 ± 3.1 μmol/d, fractional catabolic rate was 6.0% ± 2.3%/d, and vitamin A stores were 123 ± 71 μmol. Relative β-carotene bioefficacy, based on the ratio of the areas under the fraction of dose curves calculated by WinSAAM, averaged 13.5% ± 6.02% (retinol activity equivalents = 7.7:1.0 μg). Interindividual variation in relative β-carotene bioefficacy was high (CV: 44%). Conclusions: Vitamin A kinetics in these young adults were best described by essentially the same model that had been previously developed by using data for older adults with higher vitamin A stores; differences in parameter values reflected differences in vitamin A status. Estimated β-carotene bioefficacy was relatively low but similar to previously reported estimates obtained by

  12. Functional compartmentation of the Golgi apparatus of plant cells : immunocytochemical analysis of high-pressure frozen- and freeze-substituted sycamore maple suspension culture cells.

    PubMed

    Zhang, G F; Staehelin, L A

    1992-07-01

    The Golgi apparatus of plant cells is engaged in both the processing of glycoproteins and the synthesis of complex polysaccharides. To investigate the compartmentalization of these functions within individual Golgi stacks, we have analyzed the ultrastructure and the immunolabeling patterns of high-pressure frozen and freeze-substituted suspension-cultured sycamore maple (Acer pseudoplatanus L.) cells. As a result of the improved structural preservation, three morphological types of Golgi cisternae, designated cis, medial, and trans, as well as the trans Golgi network, could be identified. The number of cis cisternae per Golgi stack was found to be fairly constant at approximately 1, whereas the number of medial and trans cisternae per stack was variable and accounted for the varying number of cisternae (3-10) among the many Golgi stacks examined. By using a battery of seven antibodies whose specific sugar epitopes on secreted polysaccharides and glycoproteins are known, we have been able to determine in which types of cisternae specific sugars are added to N-linked glycans, and to xyloglucan and polygalacturonic acid/rhamnogalacturonan-I, two complex polysaccharides. The findings are as follows. The beta-1,4-linked d-glucosyl backbone of xyloglucan is synthesized in trans cisternae, and the terminal fucosyl residues on the trisaccharide side chains of xyloglucan are partly added in the trans cisternae, and partly in the trans Golgi network. In contrast, the polygalacturonic/rhamnogalacturonan-I backbone is assembled in cis and medial cisternae, methylesterification of the carboxyl groups of the galacturonic acid residues in the polygalacturonic acid domains occurs mostly in medial cisternae, and arabinose-containing side chains of the polygalacturonic acid domains are added to the nascent polygalacturonic acid/rhamnogalacturonan-I molecules in the trans cisternae. Double labeling experiments demonstrate that xyloglucan and polygalacturonic acid

  13. Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations

    PubMed Central

    Van Laethem, Kristel; Gomes, Perpetua; Baele, Guy; Pineda-Peña, Andrea-Clemencia; Vandamme, Anne-Mieke; Camacho, Ricardo J.; Abecasis, Ana B.

    2016-01-01

    Abstract Objective: The latest nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) is indicated for human immunodeficiency virus type-1 (HIV-1) patients initiating antiretroviral treatment, but the extent of genotypic RPV resistance in treatment-naive patients outside clinical trials is poorly defined. Study Design: This retrospective observational study of clinical data from Belgium and Portugal evaluates genotypic information from HIV-1 drug-naive patients obtained for the purpose of drug resistance testing. Rilpivirine resistance-associated mutations (RPV-RAMs) were defined based on clinical trials, phenotypic studies, and expert-based resistance algorithms. Viral susceptibility to RPV alone and to the single-tablet regimen was estimated using expert-based resistance algorithms. Results: In 4,631 HIV-1 treatment-naive patients infected with diverse HIV-1 subtypes, major RPV-RAMs were detected in 4.6%, while complete viral susceptibility to RPV was estimated in 95% of patients. Subtype C- and F1-infected patients displayed the highest levels of reduced viral susceptibility at baseline, respectively 13.2% and 9.3%, mainly due to subtype- and geographic-dependent occurrence of RPV-RAMs E138A and A98G as natural polymorphisms. Strikingly, a founder effect in Portugal resulted in a 138A prevalence of 13.2% in local subtype C-infected treatment-naive patients. The presence of transmitted drug resistance did not impact our estimates. Conclusion: RPV is the first HIV-1 inhibitor for which, in the absence of transmitted drug resistance, intermediate or high-level genotypic resistance can be detected in treatment-naive patients. The extent of RPV susceptibility in treatment-naive patients differs depending on the HIV-1 subtype and dynamics of local compartmentalized epidemics. The highest prevalence of reduced susceptibility was found to be 15.7% in Portuguese subtype C-infected treatment-naive patients. In this context, even in the absence of

  14. The Nuclear Power and Nuclear Weapons Connection.

    ERIC Educational Resources Information Center

    Leventhal, Paul

    1990-01-01

    Explains problems enforcing the Nuclear Non-Proliferation Treaty (NPT) of 1968. Provides factual charts and details concerning the production of nuclear energy and arms, the processing and disposal of waste products, and outlines the nuclear fuel cycle. Discusses safeguards, the risk of nuclear terrorism, and ways to deal with these problems. (NL)

  15. The nuclear arsenals and nuclear disarmament.

    PubMed

    Barnaby, F

    1998-01-01

    Current world stockpiles of nuclear weapons and the status of treaties for nuclear disarmament and the ultimate elimination of nuclear weapons are summarised. The need for including stockpiles of civil plutonium in a programme for ending production and disposing of fissile materials is emphasized, and the ultimate difficulty of disposing of the last few nuclear weapons discussed.

  16. The Nuclear Power/Nuclear Weapons Connection.

    ERIC Educational Resources Information Center

    Totten, Sam; Totten, Martha Wescoat

    1985-01-01

    Once they have nuclear power, most countries will divert nuclear materials from commercial to military programs. In excerpts from the book "Facing the Danger" (by Totten, S. and M. W., Crossing Press, 1984), five anti-nuclear activists explain how and why they have been addressing the nuclear connection. (RM)

  17. Trypanosoma cruzi DNA replication includes the sequential recruitment of pre-replication and replication machineries close to nuclear periphery

    PubMed Central

    Calderano, Simone Guedes; de Melo Godoy, Patrícia Diogo; Motta, Maria Cristina M; Mortara, Renato A; Schenkman, Sergio

    2011-01-01

    In eukaryotes, many nuclear processes are spatially compartmentalized. Previously, we have shown that in Trypanosoma cruzi, an early-divergent eukaryote, DNA replication occurs at the nuclear periphery where chromosomes remain constrained during the S phase of the cell cycle. We followed Orc1/Cdc6, a pre-replication machinery component and the proliferating cell nuclear antigen (PCNA), a component of replication machinery, during the cell cycle of this protozoon. We found that, at the G1 stage, TcOrc1/Cdc6 and TcPCNA are dispersed throughout the nuclear space. During the G1/S transition, TcOrc1/Cdc6 migrates to a region close to nuclear periphery. At the onset of S phase, TcPCNA is loaded onto the DNA and remains constrained close to nuclear periphery. Finally, in G2, mitosis and cytokinesis, TcOrc1/Cdc6 and TcPCNA are dispersed throughout the nuclear space. Based on these findings, we propose that DNA replication in T. cruzi is accomplished by the organization of functional machineries in a spatial-temporal manner. PMID:21738836

  18. Compartment-specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition

    PubMed Central

    Miller, Stephanie BM; Ho, Chi-Ting; Winkler, Juliane; Khokhrina, Maria; Neuner, Annett; Mohamed, Mohamed YH; Guilbride, D Lys; Richter, Karsten; Lisby, Michael; Schiebel, Elmar; Mogk, Axel; Bukau, Bernd

    2015-01-01

    Disruption of the functional protein balance in living cells activates protective quality control systems to repair damaged proteins or sequester potentially cytotoxic misfolded proteins into aggregates. The established model based on Saccharomyces cerevisiae indicates that aggregating proteins in the cytosol of eukaryotic cells partition between cytosolic juxtanuclear (JUNQ) and peripheral deposits. Substrate ubiquitination acts as the sorting principle determining JUNQ deposition and subsequent degradation. Here, we show that JUNQ unexpectedly resides inside the nucleus, defining a new intranuclear quality control compartment, INQ, for the deposition of both nuclear and cytosolic misfolded proteins, irrespective of ubiquitination. Deposition of misfolded cytosolic proteins at INQ involves chaperone-assisted nuclear import via nuclear pores. The compartment-specific aggregases, Btn2 (nuclear) and Hsp42 (cytosolic), direct protein deposition to nuclear INQ and cytosolic (CytoQ) sites, respectively. Intriguingly, Btn2 is transiently induced by both protein folding stress and DNA replication stress, with DNA surveillance proteins accumulating at INQ. Our data therefore reveal a bipartite, inter-compartmental protein quality control system linked to DNA surveillance via INQ and Btn2. PMID:25672362

  19. Restoration of nuclear-import failure caused by triple A syndrome and oxidative stress

    SciTech Connect

    Kiriyama, Takao; Hirano, Makito Asai, Hirohide; Ikeda, Masanori; Furiya, Yoshiko; Ueno, Satoshi

    2008-10-03

    Triple A syndrome is an autosomal recessive neurological disease, mimicking motor neuron disease, and is caused by mutant ALADIN, a nuclear-pore complex component. We recently discovered that the pathogenesis involved impaired nuclear import of DNA repair proteins, including DNA ligase I and the cerebellar ataxia causative protein aprataxin. Such impairment was overcome by fusing classical nuclear localization signal (NLS) and 137-aa downstream sequence of XRCC1, designated stretched NLS (stNLS). We report here that the minimum essential sequence of stNLS (mstNLS) is residues 239-276, downsized by more than 100 aa. mstNLS enabled efficient nuclear import of DNA repair proteins in patient fibroblasts, functioned under oxidative stress, and reduced oxidative-stress-induced cell death, more effectively than stNLS. The stress-tolerability of mstNLS was also exerted in control fibroblasts and neuroblastoma cells. These findings may help develop treatments for currently intractable triple A syndrome and other oxidative-stress-related neurological diseases, and contribute to nuclear compartmentalization study.

  20. Differential localization of 5- and 15-lipoxygenases to the nuclear envelope in RAW macrophages.

    PubMed

    Christmas, P; Fox, J W; Ursino, S R; Soberman, R J

    1999-09-01

    Leukotriene formation is initiated in myeloid cells by an increase in intracellular calcium and translocation of 5-lipoxygenase from the cytoplasm to the nuclear envelope where it can utilize arachidonic acid. Monocyte- macrophages and eosinophils also express 15-lipoxygenase, which converts arachidonic acid to 15(S)-hydroxyeicosatetraenoic acid. Enhanced green fluorescent 5-lipoxygenase (5-LO) and 15-lipoxygenase (15-LO) fusion proteins were expressed in the cytoplasm of RAW 264.7 macrophages. Only 5-lipoxygenase translocated to the nuclear envelope after cell stimulation, suggesting that differential subcellular compartmentalization can regulate the generation of leukotrienes versus 15(S)-hydroxyeicosatetraenoic acid in cells that possess both lipoxygenases. A series of truncation mutants of 5-LO were created to identify putative targeting domains; none of these mutants localized to the nuclear envelope. The lack of targeting of 15-LO was then exploited to search for specific targeting motifs in 5-LO, by creating 5-LO/15-LO chimeric molecules. The only chimera that could sustain nuclear envelope translocation was one which involved replacement of the N-terminal 237 amino acids with the corresponding segment of 15-LO. Significantly, no discrete targeting domain could be identified in 5-LO, suggesting that sequences throughout the molecule are required for nuclear envelope localization.