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Sample records for activation function af-2

  1. Activation function 2 (AF-2) of retinoic acid receptor and 9-cis retinoic acid receptor: presence of a conserved autonomous constitutive activating domain and influence of the nature of the response element on AF-2 activity.

    PubMed Central

    Durand, B; Saunders, M; Gaudon, C; Roy, B; Losson, R; Chambon, P

    1994-01-01

    A motif essential for the transcriptional activation function 2 (AF-2) present in the E region of retinoic acid receptor (RAR) alpha and 9-cis retinoic acid receptor (RXR) alpha has been characterized as an amphipathic alpha-helix whose main features are conserved between transcriptionally active members of the nuclear receptor superfamily. This conserved motif, which can activate autonomously in the absence of ligand in animal and yeast cells, can be swapped between nuclear receptors without affecting the ligand dependency for activation of transcription, thus indicating that a ligand-dependent conformational change is necessary to reveal the AF-2 activation potential within the E region of the nuclear receptor. Interestingly, we show that the precise nature of the direct repeat response element to which RAR/RXR heterodimers are bound can affect the activity of the AF-2s of the heterodimeric partners, as well as the relative efficiency with which all-trans and 9-cis retinoic acids activate the RAR partner. Images PMID:7957103

  2. Role of the essential yeast protein PSU1 in p6anscriptional enhancement by the ligand-dependent activation function AF-2 of nuclear receptors.

    PubMed Central

    Gaudon, C; Chambon, P; Losson, R

    1999-01-01

    Nuclear receptors (NRs) can function as ligandinducible transregulators in both mammalian and yeast cells, indicating that important features of transcriptional control have been conserved throughout evolution. We report here the isolation and characterization of an essential yeast protein of unknown function, PSU1, which exhibits properties expected for a co-activator/mediator of the ligand-dependent activation function AF-2 present in the ligand-binding domain (LBD, region E) of NRs. PSU1 interacts in a ligand-dependent manner with the LBD of several NRs, including retinoic acid (RARalpha), retinoid X (RXRalpha), thyroid hormone (TRalpha), vitamin D3 (VDR) and oestrogen (ERalpha) receptors. Importantly, both in yeast and in vitro, these interactions require the integrity of the AF-2 activating domain. When tethered to a heterologous DNA-binding domain, PSU1 can activate transcription on its own. By using yeast reporter cells that express PSU1 conditionally, we show that PSU1 is required for transactivation by the AF-2 of ERalpha. Taken together these data suggest that in yeast, PSU1 is involved in ligand-dependent transactivation by NRs. Sequence analysis revealed that in addition to a highly conserved motif found in a family of MutT-related proteins, PSU1 contains several alpha-helical leucine-rich motifs sharing the consensus sequence LLxPhiL (x, any amino acid; Phi, hydrophobic amino acid) in regions that elicit either transactivation or NR-binding activity. PMID:10205176

  3. The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-raf in the oncogenic protein T18.

    PubMed Central

    Le Douarin, B; Zechel, C; Garnier, J M; Lutz, Y; Tora, L; Pierrat, P; Heery, D; Gronemeyer, H; Chambon, P; Losson, R

    1995-01-01

    Nuclear receptors (NRs) bound to response elements mediate the effects of cognate ligands on gene expression. Their ligand-dependent activation function, AF-2, presumably acts on the basal transcription machinery through intermediary proteins/mediators. We have isolated a mouse nuclear protein, TIF1, which enhances RXR and RAR AF-2 in yeast and interacts in a ligand-dependent manner with several NRs in yeast and mammalian cells, as well as in vitro. Remarkably, these interactions require the amino acids constituting the AF-2 activating domain conserved in all active NRs. Moreover, the oestrogen receptor (ER) AF-2 antagonist hydroxytamoxifen cannot promote ER-TIF1 interaction. We propose that TIF1, which contains several conserved domains found in transcriptional regulatory proteins, is a mediator of ligand-dependent AF-2. Interestingly, the TIF1 N-terminal moiety is fused to B-raf in the mouse oncoprotein T18. Images PMID:7744009

  4. Differential ligand-dependent interactions between the AF-2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1.

    PubMed Central

    vom Baur, E; Zechel, C; Heery, D; Heine, M J; Garnier, J M; Vivat, V; Le Douarin, B; Gronemeyer, H; Chambon, P; Losson, R

    1996-01-01

    Using a yeast two-hybrid system we report the isolation of a novel mouse protein, mSUG1, that interacts with retinoic acid receptor alpha (RAR alpha) both in yeast cells and in vitro in a ligand- and AF-2 activating domain (AF-2 AD)-dependent manner and show that it is a structural and functional homologue of the essential yeast protein SUG1. mSUG1 also efficiently interacts with other nuclear receptors, including oestrogen (ER), thyroid hormone (TR), Vitamin D3 (VDR) and retinoid X (RXR) receptors. By comparing the interaction properties of these receptors with mSUG1 and TIF1, we demonstrate that: (i) RXR alpha efficiently interacts with TIF1, but not with mSUG1, whereas TR alpha interacts much more efficiently with mSUG1 than with TIF1, and RAR alpha, VDR and ER efficiently interact with mSUG1 and TIF1; (ii) the amphipathic alpha-helix core of the AF-2 AD is differentially involved in interactions of RAR alpha with mSUG1 and TIF1; (iii) the AF-2 AD cores of RAR alpha and ER are similarly involved in their interaction with TIF1, but not with mSUG1. Thus, the interaction interfaces between the different receptors and either mSUG1 or TIF1 may vary depending on the nature of the receptor and the putative mediator of its AF-2 function. We discuss the possibility that mSUG1 and TIF1 may mediate the transcriptional activity of the AF-2 of nuclear receptors through different mechanisms. Images PMID:8598193

  5. AF-2 activity and recruitment of steroid receptor coactivator 1 to the estrogen receptor depend on a lysine residue conserved in nuclear receptors.

    PubMed Central

    Henttu, P M; Kalkhoven, E; Parker, M G

    1997-01-01

    Hormone-dependent transcriptional activation by nuclear receptors depends on the presence of a conserved C-terminal amphipathic alpha-helix (helix 12) in the ligand-binding domain. Here we show that a lysine residue, which is conserved in most nuclear receptors in the predicted helix 3, is also required for estrogen-dependent transactivation. The replacement of lysine 366 with alanine appreciably reduced activation function 2 (AF-2) activity without affecting steroid- or DNA-binding activity in the mouse estrogen receptor. The mutation dramatically reduced the ability of the receptor to bind steroid receptor coactivator 1 (SRC-1) but had no effect on receptor-interacting protein 140 (RIP-140) binding, indicating that while their sites of interaction overlap, they are not entirely consistent and in keeping with the proposal that the recruitment of coactivators, such as SRC-1, is required for AF-2 activity. Although the function of RIP-140 remains to be established, RIP-140 appears to be capable of recruiting the basal transcription machinery, since overexpression of the protein markedly increased the transcriptional activity of the mutant receptor. Since the lysine residue is conserved, we propose that it is required, together with residues in helix 12, to form the surface by which members of the nuclear receptor family interact with coactivators. PMID:9121431

  6. The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells.

    PubMed

    Whisenant, Thomas C; Peralta, Eigen R; Aarreberg, Lauren D; Gao, Nina J; Head, Steven R; Ordoukhanian, Phillip; Williamson, Jamie R; Salomon, Daniel R

    2015-01-01

    Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as "central" interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, "peripheral" interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly of RNA

  7. The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells

    PubMed Central

    Aarreberg, Lauren D.; Gao, Nina J.; Head, Steven R.; Ordoukhanian, Phillip; Williamson, Jamie R.; Salomon, Daniel R.

    2015-01-01

    Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as “central” interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, “peripheral” interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly

  8. Prenylation inhibitors stimulate both estrogen receptor α transcriptional activity through AF-1 and AF-2 and estrogen receptor β transcriptional activity

    PubMed Central

    Cestac, Philippe; Sarrabayrouse, Guillaume; Médale-Giamarchi, Claire; Rochaix, Philippe; Balaguer, Patrick; Favre, Gilles; Faye, Jean-Charles; Doisneau-Sixou, Sophie

    2005-01-01

    Introduction We showed in a previous study that prenylated proteins play a role in estradiol stimulation of proliferation. However, these proteins antagonize the ability of estrogen receptor (ER) α to stimulate estrogen response element (ERE)-dependent transcriptional activity, potentially through the formation of a co-regulator complex. The present study investigates, in further detail, how prenylated proteins modulate the transcriptional activities mediated by ERα and by ERβ. Methods The ERE-β-globin-Luc-SV-Neo plasmid was either stably transfected into MCF-7 cells or HeLa cells (MELN cells and HELN cells, respectively) or transiently transfected into MCF-7 cells using polyethylenimine. Cells deprived of estradiol were analyzed for ERE-dependent luciferase activity 16 hours after estradiol stimulation and treatment with FTI-277 (a farnesyltransferase inhibitor) or with GGTI-298 (a geranylgeranyltransferase I inhibitor). In HELN cells, the effect of prenyltransferase inhibitors on luciferase activity was compared after transient transfection of plasmids coding either the full-length ERα, the full-length ERβ, the AF-1-deleted ERα or the AF-2-deleted ERα. The presence of ERα was then detected by immunocytochemistry in either the nuclei or the cytoplasms of MCF-7 cells. Finally, Clostridium botulinum C3 exoenzyme treatment was used to determine the involvement of Rho proteins in ERE-dependent luciferase activity. Results FTI-277 and GGTI-298 only stimulate ERE-dependent luciferase activity in stably transfected MCF-7 cells. They stimulate both ERα-mediated and ERβ-mediated ERE-dependent luciferase activity in HELN cells, in the presence of and in the absence of estradiol. The roles of both AF-1 and AF-2 are significant in this effect. Nuclear ERα is decreased in the presence of prenyltransferase inhibitors in MCF-7 cells, again in the presence of and in the absence of estradiol. By contrast, cytoplasmic ERα is mainly decreased after treatment with FTI

  9. Evidence for impaired retinoic acid receptor-thyroid hormone receptor AF-2 cofactor activity in human lung cancer.

    PubMed Central

    Moghal, N; Neel, B G

    1995-01-01

    Retinoic acid (RA) is required for normal airway epithelial cell growth and differentiation both in vivo and in vitro. One of the earliest events following the exposure of bronchial epithelial cells to RA is the strong induction of RA receptor beta (RAR beta) mRNA. Previous work established that many lung cancer cell lines and primary tumors display abnormal RAR beta mRNA expression, most often absence or weak expression of the RAR beta 2 isoform, even after RA treatment. Restoration of RAR beta 2 into RAR beta-negative lung cancer cell lines has been reported to inhibit tumorigenicity. Since RAR beta 2 inactivation may contribute to lung cancer, we have investigated the molecular mechanism of defective RAR beta 2 expression. Nuclear run-on assays and transient transfections with RAR beta 2 promoter constructs indicate the presence of trans-acting transcriptional defects in most lung cancer cell lines, which map to the RA response element (RARE). These defects cannot be complemented by RAR-retinoid X receptor cotransfection and can be separated into two types: (i) one affecting transcription from direct repeat RAREs, but not palindromic RAREs, and (ii) another affecting transcription from both types of RARE. Studies using chimeras between RAR alpha, TR alpha, and other transcription factors suggest the existence of novel RAR-thyroid hormone receptor AF-2-specific cofactors, which are necessary for high levels of transcription. Furthermore, these factors may be frequently inactivated in human lung cancer. PMID:7791800

  10. Low strain, long life creep fatigue of AF2-1DA and INCO 718

    NASA Technical Reports Server (NTRS)

    Thakker, A. B.; Cowles, B. A.

    1983-01-01

    Two aircraft turbine disk alloys, GATORIZED AF2-DA and INCO 718 were evaluated for their low strain long life creep-fatigue behavior. Static (tensile and creep rupture) and cyclic properties of both alloys were characterized. The cntrolled strain LCF tests were conducted at 760 C (1400 F) and 649 C (1200 F) for AF2-1DA and INCO 718, respectively. Hold times were varied for tensile, compressive and tensile/compressive strain dwell (relaxation) tests. Stress (creep) hold behavior of AF2-1DA was also evaluated. Generally, INCO 718 exhibited more pronounced reduction in cyclic life due to hold than AF2-1DA. The percent reduction in life for both alloys for strain dwell tests was greater at low strain ranges (longer life regime). Changing hold time from 0 to 0.5, 2.0 and 15.0 min. resulted in corresponding reductions in life. The continuous cycle and cyclic/dwell initiation failure mechanism was predominantly transgranular for AF2-1DA and intergranular for INCO 718.

  11. Hot Isostatic Pressing/Heat Treatment of Cast Superalloy AF2-1DA, Radial Turbine Wheels.

    DTIC Science & Technology

    1980-06-01

    showing typical 19 shrinkage porosity Mag: 400X Etch: Electrolytic oxalic acid 10 Microstructure of HIPped AF2-1DA alloy 29 Mag: 400X Etch...Electrolytic oxalic acid 11 Microstructure of HIPped AF2-1DA alloy note 30 void formations form incipient melting after 2250OF hip Mag: 400X Etch: Electrolytic... oxalic acid V a.w LIST OF ILLUSTRATIONS (Continued) Figure Title Page 12 Microstructure of HIPped AF2-1DA showing effects 31 of solution heat

  12. AFS-2 FLOWSHEET MODIFICATIONS TO ADDRESS THE INGROWTH OF PU(VI) DURING METAL DISSOLUTION

    SciTech Connect

    Crapse, K.; Rudisill, T.; O'Rourke, P.; Kyser, E.

    2014-07-02

    In support of the Alternate Feed Stock Two (AFS-2) PuO{sub 2} production campaign, Savannah River National Laboratory (SRNL) conducted a series of experiments concluding that dissolving Pu metal at 95°C using a 6–10 M HNO{sub 3} solution containing 0.05–0.2 M KF and 0–2 g/L B could reduce the oxidation of Pu(IV) to Pu(VI) as compared to dissolving Pu metal under the same conditions but at or near the boiling temperature. This flowsheet was demonstrated by conducting Pu metal dissolutions at 95°C to ensure that PuO{sub 2} solids were not formed during the dissolution. These dissolution parameters can be used for dissolving both Aqueous Polishing (AP) and MOX Process (MP) specification materials. Preceding the studies reported herein, two batches of Pu metal were dissolved in the H-Canyon 6.1D dissolver to prepare feed solution for the AFS-2 PuO{sub 2} production campaign. While in storage, UV-visible spectra obtained from an at-line spectrophotometer indicated the presence of Pu(VI). Analysis of the solutions also showed the presence of Fe, Ni, and Cr. Oxidation of Pu(IV) produced during metal dissolution to Pu(VI) is a concern for anion exchange purification. Anion exchange requires Pu in the +4 oxidation state for formation of the anionic plutonium(IV) hexanitrato complex which absorbs onto the resin. The presence of Pu(VI) in the anion feed solution would require a valence adjustment step to prevent losses. In addition, the presence of Cr(VI) would result in absorption of chromate ion onto the resin and could limit the purification of Pu from Cr which may challenge the purity specification of the final PuO{sub 2} product. Initial experiments were performed to quantify the rate of oxidation of Pu(IV) to Pu(VI) (presumed to be facilitated by Cr(VI)) as functions of the HNO{sub 3} concentration and temperature in simulated dissolution solutions containing Cr, Fe, and Ni. In these simulated Pu dissolutions studies, lowering the temperature from near boiling

  13. RNA structure replaces the need for U2AF2 in splicing

    PubMed Central

    Lin, Chien-Ling; Taggart, Allison J.; Lim, Kian Huat; Cygan, Kamil J.; Ferraris, Luciana; Creton, Robbert; Huang, Yen-Tsung; Fairbrother, William G.

    2016-01-01

    RNA secondary structure plays an integral role in catalytic, ribosomal, small nuclear, micro, and transfer RNAs. Discovering a prevalent role for secondary structure in pre-mRNAs has proven more elusive. By utilizing a variety of computational and biochemical approaches, we present evidence for a class of nuclear introns that relies upon secondary structure for correct splicing. These introns are defined by simple repeat expansions of complementary AC and GT dimers that co-occur at opposite boundaries of an intron to form a bridging structure that enforces correct splice site pairing. Remarkably, this class of introns does not require U2AF2, a core component of the spliceosome, for its processing. Phylogenetic analysis suggests that this mechanism was present in the ancestral vertebrate lineage prior to the divergence of tetrapods from teleosts. While largely lost from land dwelling vertebrates, this class of introns is found in 10% of all zebrafish genes. PMID:26566657

  14. RNA structure replaces the need for U2AF2 in splicing.

    PubMed

    Lin, Chien-Ling; Taggart, Allison J; Lim, Kian Huat; Cygan, Kamil J; Ferraris, Luciana; Creton, Robbert; Huang, Yen-Tsung; Fairbrother, William G

    2016-01-01

    RNA secondary structure plays an integral role in catalytic, ribosomal, small nuclear, micro, and transfer RNAs. Discovering a prevalent role for secondary structure in pre-mRNAs has proven more elusive. By utilizing a variety of computational and biochemical approaches, we present evidence for a class of nuclear introns that relies upon secondary structure for correct splicing. These introns are defined by simple repeat expansions of complementary AC and GT dimers that co-occur at opposite boundaries of an intron to form a bridging structure that enforces correct splice site pairing. Remarkably, this class of introns does not require U2AF2, a core component of the spliceosome, for its processing. Phylogenetic analysis suggests that this mechanism was present in the ancestral vertebrate lineage prior to the divergence of tetrapods from teleosts. While largely lost from land dwelling vertebrates, this class of introns is found in 10% of all zebrafish genes.

  15. Draft Genome Sequence of Komagataeibacter intermedius Strain AF2, a Producer of Cellulose, Isolated from Kombucha Tea

    PubMed Central

    dos Santos, Renato Augusto Corrêa; Berretta, Andresa Aparecida; Barud, Hernane da Silva; Ribeiro, Sidney José Lima; González-García, Laura Natalia; Zucchi, Tiago Domingues

    2015-01-01

    Here, we present the draft genome sequence of Komagataeibacter intermedius strain AF2, which was isolated from Kombucha tea and is capable of producing cellulose, although at lower levels compared to another bacterium from the same environment, K. rhaeticus strain AF1. PMID:26634755

  16. Draft Genome Sequence of Komagataeibacter intermedius Strain AF2, a Producer of Cellulose, Isolated from Kombucha Tea.

    PubMed

    Dos Santos, Renato Augusto Corrêa; Berretta, Andresa Aparecida; Barud, Hernane da Silva; Ribeiro, Sidney José Lima; González-García, Laura Natalia; Zucchi, Tiago Domingues; Goldman, Gustavo H; Riaño-Pachón, Diego M

    2015-12-03

    Here, we present the draft genome sequence of Komagataeibacter intermedius strain AF2, which was isolated from Kombucha tea and is capable of producing cellulose, although at lower levels compared to another bacterium from the same environment, K. rhaeticus strain AF1.

  17. INTERPRETATION OF AT-LINE SPECTRA FROM AFS-2 BATCH #3 FERROUS SULFAMATE TREATMENT

    SciTech Connect

    Kyser, E.; O'Rourke, P.

    2013-12-10

    Spectra from the “at-line” spectrometer were obtained during the ferrous sulfamate (FS) valence adjustment step of AFS-2 Batch #3 on 9/18/2013. These spectra were analyzed by mathematical principal component regression (PCR) techniques to evaluate the effectiveness of this treatment. Despite the complications from Pu(IV), we conclude that all Pu(VI) was consumed during the FS treatment, and that by the end of the treatment, about 85% was as Pu(IV) and about 15% was as Pu(III). Due to the concerns about the “odd” shape of the Pu(IV) peak and the possibility of this behavior being observed in the future, a follow-up sample was sent to SRNL to investigate this further. Analysis of this sample confirmed the previous results and concluded that it “odd” shape was due to an intermediate acid concentration. Since the spectral evidence shows complete reduction of Pu(VI) we conclude that it is appropriate to proceed with processing of this the batch of feed solution for HB-Line including the complexation of the fluoride with aluminum nitrate.

  18. [Physical activity and brain function].

    PubMed

    Kempermann, G

    2012-06-01

    Physical activity has direct and indirect effects on brain function in health and disease. Findings demonstrating that physical activity improves cognitive and non-cognitive functions and is preventive for several neuropsychiatric disorders have attracted particular interest. This short review focuses on sports and physical exercise in normal brain function and summarizes which mechanisms might underlie the observed effects, which methodological problems exist, which relationships exist to concepts of plasticity and neural reserves and what evolutionary relevance the initially surprising finding that physical exercise is good for the brain has.

  19. Complement Activation Alters Platelet Function

    DTIC Science & Technology

    2013-10-01

    mice and mice transfused with Syk inhibitor-treated platelets . Platelet lodging was remarkably decreased in lungs of mice transfused with Syk...AD_________________ Award Number: W81XWH-12-1-0523 TITLE: Complement Activation Alters Platelet ...30September2012–29September2013 4. TITLE AND SUBTITLE Complement Activation Alters Platelet Function 5a. CONTRACT NUMBER W81XWH-12-1-0523 5b. GRANT NUMBER

  20. Trehalose induces functionally active conformation in the intrinsically disordered N-terminal domain of glucocorticoid receptor.

    PubMed

    Khan, Shagufta H; Jasuja, Ravi; Kumar, Raj

    2016-08-05

    Glucocorticoid receptor (GR) is a classic member of the nuclear receptor superfamily and plays pivotal roles in human physiology at the level of gene regulation. Various constellations of cellular cofactors are required to associate with GR to activate/repress genes. The effects of specific ligands on the AF2 structure and consequent preferential binding of co-activators or co-repressors have helped our understanding of the mechanisms involved. But the data so far fall short of fully explaining GR actions. We believe that this is because work so far has largely avoided detailed examination of the contributions of AF1 to overall GR actions. It has been shown that the GR containing only the N-terminal domain (NTD) and the DNA-binding domain (GR500) is constitutively quite active in stimulating transcription from simple promoters. However, we are only beginning to understand structure and functions of GR500 in spite of the fact that AF1 located within the NTD serves as major transactivation domain for GR. Lack of this information has hampered our complete understanding of how GR regulates its target gene(s). The major obstacle in determining GR500 structure has been due to its intrinsically disordered NTD conformation, frequently found in transcription factors. In this study, we tested whether a naturally occurring osmolyte, trehalose, can promote functionally ordered conformation in GR500. Our data show that in the presence of trehalose, GR500 is capable of formation of a native-like functionally folded conformation.

  1. Functionalized active-nucleus complex sensor

    DOEpatents

    Pines, Alexander; Wemmer, David E.; Spence, Megan; Rubin, Seth

    2003-11-25

    A functionalized active-nucleus complex sensor that selectively associates with one or more target species, and a method for assaying and screening for one or a plurality of target species utilizing one or a plurality of functionalized active-nucleus complexes with at least two of the functionalized active-nucleus complexes having an attraction affinity to different corresponding target species. The functionalized active-nucleus complex has an active-nucleus and a targeting carrier. The method involves functionalizing an active-nucleus, for each functionalized active-nucleus complex, by incorporating the active-nucleus into a macromolucular or molecular complex that is capable of binding one of the target species and then bringing the macromolecular or molecular complexes into contact with the target species and detecting the occurrence of or change in a nuclear magnetic resonance signal from each of the active-nuclei in each of the functionalized active-nucleus complexes.

  2. Complementary DNA cloning, sequence analysis, and tissue transcription profile of a novel U2AF2 gene from the Chinese Banna mini-pig inbred line.

    PubMed

    Wang, S Y; Huo, J L; Miao, Y W; Cheng, W M; Zeng, Y Z

    2013-04-02

    U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an important gene for pre-messenger RNA splicing in higher eukaryotes. In this study, the Banna mini-pig inbred line (BMI) U2AF2 coding sequence (CDS) was cloned, sequenced, and characterized. The U2AF2 complete CDS was amplified using the reverse transcription-polymerase chain reaction (RT-PCR) technique based on the conserved sequence information of cattle and known highly homologous swine expressed sequence tags. This novel gene was deposited into the National Center for Biotechnology Information database (Accession No. JQ839267). Sequence analysis revealed that the BMI U2AF2 coding sequence consisted of 1416 bp and encoded 471 amino acids with a molecular weight of 53.12 kDa. The protein sequence has high sequence homology with U2AF65 of 6 species - Homo sapiens (100%), Equus caballus (100%), Canis lupus (100%), Macaca mulatta (99.8%), Bos taurus (74.4%), and Mus musculus (74.4%). The phylogenetic tree analysis revealed that BMI U2AF65 has a closer genetic relationship with B. taurus U2AF65 than with U2AF65 of E. caballus, C. lupus, M. mulatta, H. sapiens, and M. musculus. RT-PCR analysis showed that BMI U2AF2 was most highly expressed in the brain; moderately expressed in the spleen, lung, muscle, and skin; and weakly expressed in the liver, kidney, and ovary. Its expression was nearly silent in the spinal cord, nerve fiber, heart, stomach, pancreas, and intestine. Three microRNA target sites were predicted in the CDS of BMI U2AF2 messenger RNA. Our results establish a foundation for further insight into this swine gene.

  3. Macrophage Biochemistry, Activation and Function

    DTIC Science & Technology

    1981-01-01

    glucoeidase +8 . . Sulfatase c +8 Modified from Morahan, 1980. b(+)Exhibit@ activity; (-) lacks activity; (+) weak or marginal activity. ’References: (1...endoplasmic reticulum enzymes, sulfatase c and alkaline a-glucosidase. Dissociation of the lysosomal enzyme patterns from sulfatase c and alkaline r...1974; Beaufay et al., 1974). Peritoneal macrophages are deficient or contain inauf- • -𔃼 :’- 41 ficient quantities of the classical constituents to be

  4. Multimorbidity, cognitive function, and physical activity.

    PubMed

    Loprinzi, Paul D

    2016-02-01

    Previous research demonstrates that both physical activity and multimorbidity are associated with cognitive function. However, the extent to which physical activity may moderate the relationship between multimorbidity and cognitive function has not been thoroughly evaluated. Data from the 1999-2002 NHANES were used (60+ years; N = 2157). A multimorbidity index variable was created based on physician diagnosis of a multitude of chronic diseases. Physical activity was self-reported and cognitive function was evaluated from the digit symbol substitution test. Multimorbidity was inversely associated with cognitive function for the unadjusted and adjusted models. However, generally, multimorbidity was no longer associated with cognitive function for the majority of older adults who achieved the minimum recommended physical activity level (≥2000 MET-min-month), as issued by the United States Department of Health and Human Services. In this national sample of older adults, there was some evidence to suggest that physical activity moderates the relationship between multimorbidity and cognitive function.

  5. Stellar Kinematics and Metallicities in the Draco and Ursa Minor Dwarf Spheroidal Galaxies from WHT/AF2-WYFFOS

    NASA Astrophysics Data System (ADS)

    Jin, S.; Irwin, M.; Tolstoy, E.; Lewis, J.; Hartke, J.

    2016-10-01

    We present preliminary results from our chemo-dynamical survey of two Milky Way dwarf spheroidal (dSph) galaxies, Draco and Ursa Minor. The two galaxies have similar radial velocities and reside in close proximity in the outskirts of the Milky Way halo, yet exhibit noteworthy differences in their morphologies. We obtained spectroscopic data with AF2-WYFFOS on the WHT for several hundred red-giant-branch (RGB) candidates in each galaxy out to its tidal radius, from which we have identified approximately 100 velocity members in each system. Metallicities are determined for the individual RGB stars using the Ca II triplet lines. Whereas Ursa Minor shows an RGB population of well-mixed metallicities, a clear gradient is observed in Draco, in which the outer regions host stars of lower [Fe/H]. Such differences may be a reflection of their differing morphologies, with Ursa Minor having been tidally stirred to give rise to both its highly elongated shape and a more mixed [Fe/H] distribution.

  6. Native functions of the androgen receptor are essential to pathogenesis in a Drosophila model of spinobulbar muscular atrophy

    PubMed Central

    Nedelsky, Natalia B.; Pennuto, Maria; Smith, Rebecca B.; Palazzolo, Isabella; Moore, Jennifer; Nie, Zhiping; Neale, Geoffrey; Taylor, J. Paul

    2012-01-01

    Summary Spinobulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by expansion of a polyglutamine tract in the androgen receptor (AR). This mutation confers toxic function to AR through unknown mechanisms. Mutant AR toxicity requires binding of its hormone ligand, suggesting that pathogenesis involves ligand-induced changes in AR. However, whether toxicity is mediated by native AR function or a novel AR function is unknown. We systematically investigated events downstream of ligand-dependent AR activation in a Drosophila model of SBMA. We show that nuclear translocation of AR is necessary but not sufficient for toxicity and that DNA binding by AR is necessary for toxicity. Mutagenesis studies demonstrated that a functional AF-2 domain is essential for toxicity, a finding corroborated by a genetic screen that identified AF-2 interactors as dominant modifiers of degeneration. These findings indicate that SBMA pathogenesis is mediated by misappropriation of native protein function, a mechanism that may apply broadly to polyglutamine diseases. PMID:20869592

  7. Partial androgen insensitivity with phenotypic variation caused by androgen receptor mutations that disrupt activation function 2 and the NH(2)- and carboxyl-terminal interaction.

    PubMed

    Quigley, Charmian A; Tan, Jiann-an; He, Bin; Zhou, Zhong-xun; Mebarki, Farida; Morel, Yves; Forest, Maguelone G; Chatelain, Pierre; Ritzén, E Martin; French, Frank S; Wilson, Elizabeth M

    2004-01-01

    Partial androgen insensitivity with sex phenotype variation in two unrelated families was associated with missense mutations in the androgen receptor (AR) gene that disrupted the AR NH(2)-terminal/carboxy terminal interaction. Each mutation caused a single amino acid change within the region of the ligand-binding domain that forms activation function 2 (AF2). In one family, the mutation I737T was in alpha helix 4 and in the other F725L was between helices 3 and 4. Neither mutation altered androgen binding as determined by assays of mutant AR in the patient's cultured genital skin fibroblasts or of recombinant mutant receptors transfected into COS cells. In transient cotransfection assays in CV1 cells, transactivation with the AR mutants at low concentrations of DHT was reduced several fold compared with wild-type AR but increased at higher concentrations. Defects in NH(2)-terminal/carboxy terminal interactions were identified in mammalian two hybrid assays. In similar assays, there was reduced binding of the p160 coactivators TIF2/SRC2 and SRC1 to the mutant AR ligand binding domains (LBD). In the family with AR I737T, sex phenotype varied from severely defective masculinization in the proband to a maternal great uncle whose only manifestation of AIS was severe gynecomastia. He was fertile and passed the mutation to two daughters. The proband of the F725L family was also incompletely masculinized but was raised as a male while his half-sibling by a different father was affected more severely and reared as a female. These studies indicate that the function of an AR AF2 mutant in male development can vary greatly depending on the genetic background.

  8. Opiates and cerebral functional activity in rats

    SciTech Connect

    Trusk, T.C.

    1986-01-01

    Cerebral activity was measured using the free-fatty acid (1-/sup 14/C) octanoate as a fast functional tracer in conscious, unrestrained rats 5 minutes after intravenous injection of heroin, cocaine or saline vehicle. Regional changes of octanoate labeling density in the autoradiograms relative to saline-injected animals were used to determine the functional activity effects of each drug. Heroin and cocaine each produced a distinctive pattern of activity increases and suppression throughout the rat brain. Similar regional changes induced by both drugs were found in limbic brain regions implicated in drug reinforcement. Labeled octanoate autoradiography was used to measure the cerebral functional response to a tone that had previously been paired to heroin injections. Rats were trained in groups of three consisting of one heroin self-administration animal, and two animals receiving yoked infusion of heroin or saline. A tone was paired with each infusion during training. Behavioral experiments in similarly trained rats demonstrated that these training conditions impart secondary reinforcing properties to the tone in animals previously self-administering heroin, while the tone remains behaviorally neutral in yoked-infusion rats. Cerebral functional activity was measured during presentation of the tone without drug infusion. Octanoate labeling density changed in fifteen brain areas in response to the tone previously paired to heroin without response contingency. Labeling density was significantly modified in sixteen regions as a result of previously pairing the tone to response-contingent heroin infusions.

  9. Cerebral blood flow response to functional activation

    PubMed Central

    Paulson, Olaf B; Hasselbalch, Steen G; Rostrup, Egill; Knudsen, Gitte Moos; Pelligrino, Dale

    2010-01-01

    Cerebral blood flow (CBF) and cerebral metabolic rate are normally coupled, that is an increase in metabolic demand will lead to an increase in flow. However, during functional activation, CBF and glucose metabolism remain coupled as they increase in proportion, whereas oxygen metabolism only increases to a minor degree—the so-called uncoupling of CBF and oxidative metabolism. Several studies have dealt with these issues, and theories have been forwarded regarding the underlying mechanisms. Some reports have speculated about the existence of a potentially deficient oxygen supply to the tissue most distant from the capillaries, whereas other studies point to a shift toward a higher degree of non-oxidative glucose consumption during activation. In this review, we argue that the key mechanism responsible for the regional CBF (rCBF) increase during functional activation is a tight coupling between rCBF and glucose metabolism. We assert that uncoupling of rCBF and oxidative metabolism is a consequence of a less pronounced increase in oxygen consumption. On the basis of earlier studies, we take into consideration the functional recruitment of capillaries and attempt to accommodate the cerebral tissue's increased demand for glucose supply during neural activation with recent evidence supporting a key function for astrocytes in rCBF regulation. PMID:19738630

  10. Functional activities of the amygdala: an overview.

    PubMed Central

    Rasia-Filho, A A; Londero, R G; Achaval, M

    2000-01-01

    Research to date into the amygdala shows that it has an integrative role in behavioural, vegetative and endocrine activities of animals in their relation with their environment. Animal studies show that amygdala has a role in emotional response, integrating input signals and initiating activities related to them. Different nuclei seem to have different effects. A complete picture of the functional roles of the amygdala is unavailable, and it has been suggested that the amygdala is functionally and anatomically heterogeneous. Amygdaloid subnuclei appear to have a role in the modulation of fear, in memory and attention, and in some sexual and sex-related behaviour of rats. In humans, functional magnetic resonance imaging shows that the amygdala responds preferentially to emotionally charged stimuli. Bilateral amygdala damage in humans can compromise the recognition of fear in facial expressions, an important ability in social judgement. Future study of the amygdala promises to shed light on emotional disorders in humans. PMID:10721680

  11. Deep Neural Networks with Multistate Activation Functions

    PubMed Central

    Cai, Chenghao; Xu, Yanyan; Ke, Dengfeng; Su, Kaile

    2015-01-01

    We propose multistate activation functions (MSAFs) for deep neural networks (DNNs). These MSAFs are new kinds of activation functions which are capable of representing more than two states, including the N-order MSAFs and the symmetrical MSAF. DNNs with these MSAFs can be trained via conventional Stochastic Gradient Descent (SGD) as well as mean-normalised SGD. We also discuss how these MSAFs perform when used to resolve classification problems. Experimental results on the TIMIT corpus reveal that, on speech recognition tasks, DNNs with MSAFs perform better than the conventional DNNs, getting a relative improvement of 5.60% on phoneme error rates. Further experiments also reveal that mean-normalised SGD facilitates the training processes of DNNs with MSAFs, especially when being with large training sets. The models can also be directly trained without pretraining when the training set is sufficiently large, which results in a considerable relative improvement of 5.82% on word error rates. PMID:26448739

  12. Vestibular Function and Activities of Daily Living

    PubMed Central

    Harun, Aisha; Semenov, Yevgeniy R.; Agrawal, Yuri

    2015-01-01

    Objective: Vestibular dysfunction increases with age and is associated with mobility difficulties and fall risk in older individuals. We evaluated whether vestibular function influences the ability to perform activities of daily living (ADLs). Method: We analyzed the 1999 to 2004 National Health and Nutrition Examination Survey of adults aged older than 40 years (N = 5,017). Vestibular function was assessed with the Modified Romberg test. We evaluated the association between vestibular function and difficulty level in performing specific basic and instrumental ADLs, and total number of ADL impairments. Results: Vestibular dysfunction was associated with significantly higher odds of difficulty with nine ADLs, most strongly with difficulty managing finances (odds ratio [OR] = 2.64, 95% confidence interval [CI] = [1.18, 5.90]). In addition, vestibular dysfunction was associated with a significantly greater number of ADL impairments (β = .21, 95% CI = [0.09, 0.33]). This effect size was comparable with the influence of heavy smoking (β = .21, 95% CI = [0.06, 0.36]) and hypertension (β = .10, 95% CI = [0.02, 0.18]) on the number of ADL impairments. Conclusion: Vestibular dysfunction significantly influences ADL difficulty, most strongly with a cognitive rather than mobility-based task. These findings underscore the importance of vestibular inputs for both cognitive and physical daily activities. PMID:26753170

  13. Functions for diverse metabolic activities in heterochromatin

    PubMed Central

    Su, Xue Bessie; Pillus, Lorraine

    2016-01-01

    Growing evidence demonstrates that metabolism and chromatin dynamics are not separate processes but that they functionally intersect in many ways. For example, the lysine biosynthetic enzyme homocitrate synthase was recently shown to have unexpected functions in DNA damage repair, raising the question of whether other amino acid metabolic enzymes participate in chromatin regulation. Using an in silico screen combined with reporter assays, we discovered that a diverse range of metabolic enzymes function in heterochromatin regulation. Extended analysis of the glutamate dehydrogenase 1 (Gdh1) revealed that it regulates silent information regulator complex recruitment to telomeres and ribosomal DNA. Enhanced N-terminal histone H3 proteolysis is observed in GDH1 mutants, consistent with telomeric silencing defects. A conserved catalytic Asp residue is required for Gdh1’s functions in telomeric silencing and H3 clipping. Genetic modulation of α-ketoglutarate levels demonstrates a key regulatory role for this metabolite in telomeric silencing. The metabolic activity of glutamate dehydrogenase thus has important and previously unsuspected roles in regulating chromatin-related processes. PMID:26936955

  14. Functions for diverse metabolic activities in heterochromatin.

    PubMed

    Su, Xue Bessie; Pillus, Lorraine

    2016-03-15

    Growing evidence demonstrates that metabolism and chromatin dynamics are not separate processes but that they functionally intersect in many ways. For example, the lysine biosynthetic enzyme homocitrate synthase was recently shown to have unexpected functions in DNA damage repair, raising the question of whether other amino acid metabolic enzymes participate in chromatin regulation. Using an in silico screen combined with reporter assays, we discovered that a diverse range of metabolic enzymes function in heterochromatin regulation. Extended analysis of the glutamate dehydrogenase 1 (Gdh1) revealed that it regulates silent information regulator complex recruitment to telomeres and ribosomal DNA. Enhanced N-terminal histone H3 proteolysis is observed in GDH1 mutants, consistent with telomeric silencing defects. A conserved catalytic Asp residue is required for Gdh1's functions in telomeric silencing and H3 clipping. Genetic modulation of α-ketoglutarate levels demonstrates a key regulatory role for this metabolite in telomeric silencing. The metabolic activity of glutamate dehydrogenase thus has important and previously unsuspected roles in regulating chromatin-related processes.

  15. Exercise Sandals Increase Lower Extremity Electromyographic Activity During Functional Activities

    PubMed Central

    Hirth, Christopher J.; Guskiewicz, Kevin M.

    2003-01-01

    Objective: Anecdotal evidence suggests that use of Exercise Sandals results in a number of positive clinical outcomes. However, little research has been conducted to determine their efficacy objectively. Our purposes were to determine the effect of Exercise Sandals on lower leg electromyography (EMG) during activities in the Exercise Sandals and to compare EMG associated with Exercise Sandals with traditional lower extremity rehabilitation exercises. Design and Setting: Two within-subjects, repeated-measures designs were used to identify differences in lower extremity EMG: (1) between activities with and without Exercise Sandals and (2) between Exercise Sandals activities and traditional rehabilitation activities. All data were collected in the Sports Medicine Research Laboratory. Subjects: Eighteen subjects involved in rehabilitation using Exercise Sandals for at least 2 weeks within the year before data collection. Measurements: Mean EMG amplitudes from the tibialis anterior, peroneus longus, soleus, and lateral gastrocnemius muscles were measured during single-leg stance, side stepping, and “high knees,” all performed with and without the Exercise Sandals, as well as single-leg stance on a foam surface and T-band kicks in the sagittal and frontal planes. Results: Exercise Sandals increased lower leg EMG activity, particularly in the ankle invertors and evertors. Also, activities involving the Exercise Sandals resulted in EMG activity similar to or exceeding that associated with traditional ankle-rehabilitation exercises. Conclusions: These results, coupled with the fact that Exercise Sandals are used in a functional closed kinetic chain manner, suggest that they are an effective means of increasing lower extremity muscle activity. PMID:14608427

  16. Cardiovascular function following reduced aerobic activity

    NASA Technical Reports Server (NTRS)

    Raven, P. B.; Welch-O'Connor, R. M.; Shi, X.; Blomqvist, C. G. (Principal Investigator)

    1998-01-01

    PURPOSE: The aim of this study was to test the hypothesis that a sustained reduction of physical activity (deconditioning) would alter the cardiovascular regulatory function. METHODS: Nineteen young, healthy volunteers participated in physical deconditioning for a period of 8 wk. Before (pre) and following (post) physical deconditioning, the responses of heart rate (HR), mean arterial pressure (MAP, measured by Finapres), central venous pressure (CVP), stroke volume (SV, Doppler), and forearm blood flow (FBF, plethysmography) were determined during lower body negative pressure (LBNP). The carotid baroreflex (CBR) function was assessed using a train of pulsatile neck pressure (NP) and suction, and the aortic baroreflex control of HR was assessed during steady-state phenylephrine (PE) infusion superimposed by LBNP and NP to counteract the PE increased CVP and carotid sinus pressure, respectively. RESULTS: Active physical deconditioning significantly decreased maximal oxygen uptake (-7%) and LBNP tolerance (-13%) without a change in baseline hemodynamics. Plasma volume (-3% at P = 0.135), determined by Evans Blue dilution, and blood volume (-4% at P = 0.107) were not significantly altered. During LBNP -20 to -50 torr, there was a significantly greater drop of SV per unit decrease in CVP in the post- (14.7 +/- 1.6%/mm Hg) than predeconditioning (11.2 +/- 0.7%/mm Hg) test accompanied by a greater tachycardia. Deconditioning increased the aortic baroreflex sensitivity (pre vs post: -0.61 +/- 0.12 vs -0.84 +/- 0.14 bpm.mm-1 Hg, P = 0.009) and the slope of forearm vascular resistance (calculated from [MAP-CVP]/FBF) to CVP (-2.75 +/- 0.26 vs -4.94 +/- 0.97 PRU/mm Hg, P = 0.086). However, neither the CBR-HR (-0.28 +/- 0.03 VS -0.39 +/- 0.10 bpm.mm-1 Hg) nor the CBR-MAP (-0.37 +/- 0.16 vs -0.25 +/- 0.07 mm Hg/mm Hg) gains were statistically different between pre- and postdeconditioning. CONCLUSIONS: We concluded that the functional modification of the cardiac pressure

  17. BK channel activation: structural and functional insights

    PubMed Central

    Lee, Urvi S.; Cui, Jianmin

    2010-01-01

    The voltage and Ca2+ activated K+ (BK) channels are involved in the regulation of neurotransmitter release and neuronal excitability. Structurally, BK channels are homologous to voltage- and ligand-gated K+ channels, having a voltage sensor and pore as the membrane-spanning domain and a cytosolic domain containing metal binding sites. Recently published electron cryomicroscopy (cryo-EM) and X-ray crystallographic structures of the BK channel provided the first look into the assembly of these domains, corroborating the close interactions among these domains during channel gating that have been suggested by functional studies. This review discusses these latest findings and an emerging new understanding about BK channel gating and implications for diseases such as epilepsy, in which mutations in BK channel genes have been associated. PMID:20663573

  18. Measurement of functional activities in older adults in the community.

    PubMed

    Pfeffer, R I; Kurosaki, T T; Harrah, C H; Chance, J M; Filos, S

    1982-05-01

    Two measures of social function designed for community studies of normal aging and mild senile dementia were evaluated in 195 older adults who underwent neurological, cognitive, and affective assessment. An examining and a reviewing neurologist and a neurologically trained nurse independently rated each on a Scale of Functional Capacity. Interrater reliability was high (examining vs. reviewing neurologist, r = .97; examining neurologist vs. nurse, tau b = .802; p less than .001 for both comparisons). Estimates correlated well with an established measure of social function and with results of cognitive tests. Alternate informants evaluated participants on the Functional Activities Questionnaire and the Instrumental Activities of Daily Living Scale. The Functional Activities Questionnaire was superior to the Instrumental Activities of Daily scores. Used alone as a diagnostic tool, the Functional Activities Questionnaire was more sensitive than distinguishing between normal and demented individuals.

  19. Functional analysis of retinoid Z receptor beta, a brain-specific nuclear orphan receptor.

    PubMed Central

    Greiner, E F; Kirfel, J; Greschik, H; Dörflinger, U; Becker, P; Mercep, A; Schüle, R

    1996-01-01

    The retinoid Z receptor beta (RZR beta), an orphan receptor, is a member of the retinoic acid receptor (RAR)/thyroid hormone receptor (TR) subfamily of nuclear receptors. RZR beta exhibits a highly restricted brain-specific expression pattern. So far, no natural RZR beta target gene has been identified and the physiological role of the receptor in transcriptional regulation remains to be elucidated. Electrophoretic mobility shift assays reveal binding of RZR beta to monomeric response elements containing the sequence AnnTAGGTCA, but RZR beta-mediated transactivation of reporter genes is only achieved with two property spaced binding sites. We present evidence that RZR beta can function as a cell-type-specific transactivator. In neuronal cells, GaI-RZR beta fusion proteins function as potent transcriptional activators, whereas no transactivation can be observed in nonneuronal cells. Mutational analyses demonstrate that the activation domain (AF-2) of RZR beta and RAR alpha are functionally interchangeable. However, in contrast to RAR and TR, the RZR beta AF-2 cannot function autonomously as a transactivation domain. Furthermore, our data define a novel repressor function for the C-terminal part of the putative ligand binding domain. We propose that the transcriptional activity of RZR beta is regulated by an interplay of different receptor domains with coactivators and corepressors. Images Fig. 5 PMID:8816759

  20. Hydrogen adsorption on functionalized nanoporous activated carbons.

    PubMed

    Zhao, X B; Xiao, B; Fletcher, A J; Thomas, K M

    2005-05-12

    There is considerable interest in hydrogen adsorption on carbon nanotubes and porous carbons as a method of storage for transport and related energy applications. This investigation has involved a systematic investigation of the role of functional groups and porous structure characteristics in determining the hydrogen adsorption characteristics of porous carbons. Suites of carbons were prepared with a wide range of nitrogen and oxygen contents and types of functional groups to investigate their effect on hydrogen adsorption. The porous structures of the carbons were characterized by nitrogen (77 K) and carbon dioxide (273 K) adsorption methods. Hydrogen adsorption isotherms were studied at 77 K and pressure up to 100 kPa. All the isotherms were Type I in the IUPAC classification scheme. Hydrogen isobars indicated that the adsorption of hydrogen is very temperature dependent with little or no hydrogen adsorption above 195 K. The isosteric enthalpies of adsorption at zero surface coverage were obtained using a virial equation, while the values at various surface coverages were obtained from the van't Hoff isochore. The values were in the range 3.9-5.2 kJ mol(-1) for the carbons studied. The thermodynamics of the adsorption process are discussed in relation to temperature limitations for hydrogen storage applications. The maximum amounts of hydrogen adsorbed correlated with the micropore volume obtained from extrapolation of the Dubinin-Radushkevich equation for carbon dioxide adsorption. Functional groups have a small detrimental effect on hydrogen adsorption, and this is related to decreased adsorbate-adsorbent and increased adsorbate-adsorbate interactions.

  1. Usage Of New Activation Function In Neuro-Symbolic Integration

    SciTech Connect

    Sathasivam, Saratha

    2010-12-23

    New activation function is examined for its ability to accelerate the performance of doing logic programming in Hopfield network. This method has a higher capacity and upgrades the neuro symbolic integration. Computer simulations are carried out to validate the effectiveness of the new activation function. Empirical results obtained support our theory.

  2. Caspase activation inhibits proteasome function during apoptosis.

    PubMed

    Sun, Xiao-Ming; Butterworth, Michael; MacFarlane, Marion; Dubiel, Wolfgang; Ciechanover, Aaron; Cohen, Gerald M

    2004-04-09

    The ubiquitin/proteasome system regulates protein turnover by degrading polyubiquitinated proteins. To date, all studies on the relationship of apoptosis and the proteasome have emphasized the key role of the proteasome in the regulation of apoptosis, by virtue of its ability to degrade regulatory molecules involved in apoptosis. We now demonstrate how induction of apoptosis may regulate the activity of the proteasome. During apoptosis, caspase activation results in the cleavage of three specific subunits of the 19S regulatory complex of the proteasome: S6' (Rpt5) and S5a (Rpn10), whose role is to recognize polyubiquitinated substrates of the proteasome, and S1 (Rpn2), which with S5a and S2 (Rpn1) holds together the lid and base of the 19S regulatory complex. This caspase-mediated cleavage inhibits the proteasomal degradation of ubiquitin-dependent and -independent cellular substrates, including proapoptotic molecules such as Smac, so facilitating the execution of the apoptotic program by providing a feed-forward amplification loop.

  3. Graves' disease: thyroid function and immunologic activity

    SciTech Connect

    Gossage, A.A.; Crawley, J.C.; Copping, S.; Hinge, D.; Himsworth, R.L.

    1982-11-01

    Patients with Graves' disease were studied for two years during and after a twelve-month course of treatment. Disease activity was determined by repeated measurements of thyroidal uptake of (/sup 99m/Tc)pertechnetate during tri-iodothyronine administration. These in-vivo measurements of thyroid stimulation were compared with the results of in-vitro assays of Graves, immunoglobulin (TSH binding inhibitory activity--TBIA). There was no correlation between the thyroid uptake and TBIA on diagnosis. Pertechnetate uptake and TBIA both declined during the twelve months of antithyroid therapy. TBIA was detectable in sera from 19 of the 27 patients at diagnosis; in 11 of these 19 patients there was a good correlation (p less than 0.05) throughout the course of their disease between the laboratory assay of the Graves, immunoglobulin and the thyroid uptake. Probability of recurrence can be assessed but sustained remission of Graves' disease after treatment cannot be predicted from either measurement alone or in combination.

  4. Assessing physical function and physical activity in patients with CKD.

    PubMed

    Painter, Patricia; Marcus, Robin L

    2013-05-01

    Patients with CKD are characterized by low levels of physical functioning, which, along with low physical activity, predict poor outcomes in those treated with dialysis. The hallmark of clinical care in geriatric practice and geriatric research is the orientation to and assessment of physical function and functional limitations. Although there is increasing interest in physical function and physical activity in patients with CKD, the nephrology field has not focused on this aspect of care. This paper provides an in-depth review of the measurement of physical function and physical activity. It focuses on physiologic impairments and physical performance limitations (impaired mobility and functional limitations). The review is based on established frameworks of physical impairment and functional limitations that have guided research in physical function in the aging population. Definitions and measures for physiologic impairments, physical performance limitations, self-reported function, and physical activity are presented. On the basis of the information presented, recommendations for incorporating routine assessment of physical function and encouragement for physical activity in clinical care are provided.

  5. Physical activity and cognitive function in bariatric surgery candidates.

    PubMed

    Galioto, Rachel; King, Wendy C; Bond, Dale S; Spitznagel, Mary Beth; Strain, Gladys; Devlin, Michael; Cohen, Ronald; Crosby, Ross D; Mitchell, James E; Gunstad, John

    2014-12-01

    Cognitive impairment is common in severe obesity. Lack of physical activity is a likely contributor to impairment in this population, as many obese persons are inactive and physical activity has been positively and independently associated with cognitive function in healthy and medically-ill samples. This study investigated whether physical activity, measured by self-report of aerobic physical activity in 85 bariatric surgery candidates, was associated with cognitive function. A subset of 31 participants also completed objective activity monitoring. Steps/d and high-cadence min/week, representative of ambulatory moderate to vigorous physical activity (MVPA), were calculated. Approximately one quarter of participants self-reported at least 30 min/d of aerobic MVPA, at least 5 d/week. Median steps/d was 7949 (IQR = 4572) and median MVPA min/week was 105 (IQR = 123). Cognitive deficits were found in 32% of participants (29% memory, 10% executive function, 13% language, 10% attention). Controlling for demographic and medical factors, self-reported aerobic physical activity was weakly correlated with lower attention (r = -0.21, p = 0.04) and executive function (r = -0.27, p < 0.01) and both self-reported aerobic physical activity and objectively-determined MVPA min/week were negatively correlated with memory (r = -0.20, p = 0.04; r = -0.46; p = 0.02, respectively). No other correlations between physical activity measures and cognitive function were significant. Contrary to expectations, greater levels of physical activity were not associated with better cognitive functioning. Such findings encourage future studies to clarify the association among cognitive function and physical activity in obese persons.

  6. Multivariate neural network operators with sigmoidal activation functions.

    PubMed

    Costarelli, Danilo; Spigler, Renato

    2013-12-01

    In this paper, we study pointwise and uniform convergence, as well as order of approximation, of a family of linear positive multivariate neural network (NN) operators with sigmoidal activation functions. The order of approximation is studied for functions belonging to suitable Lipschitz classes and using a moment-type approach. The special cases of NN operators, activated by logistic, hyperbolic tangent, and ramp sigmoidal functions are considered. Multivariate NNs approximation finds applications, typically, in neurocomputing processes. Our approach to NN operators allows us to extend previous convergence results and, in some cases, to improve the order of approximation. The case of multivariate quasi-interpolation operators constructed with sigmoidal functions is also considered.

  7. Prevalence of cry2-type genes in Bacillus thuringiensis isolates recovered from diverse habitats in India and isolation of a novel cry2Af2 gene toxic to Helicoverpa armigera (cotton boll worm).

    PubMed

    Katara, Jawahar Lal; Kaur, Sarvjeet; Kumari, Gouthami Krishna; Singh, Nagendra Kumar

    2016-12-01

    Insecticidal cry and vip genes from Bacillus thuringiensis (Bt) have been used for control of lepidopteran insects in transgenic crops. However, novel genes are required for gene pyramiding to delay evolution of resistance to the currently deployed genes. Two PCR-based techniques were employed for screening of cry2-type genes in 129 Bt isolates from diverse habitats in India and 27 known Bt strains. cry2Ab-type genes were more prevalent than cry2Aa- and cry2Ac-type genes. Correlation between source of isolates and abundance of cry2-type genes was not observed. Full-length cry2A-type genes were amplified by PCR from 9 Bt isolates and 4 Bt strains. The genes from Bt isolates SK-758 from Sorghum grain dust and SK-793 from Chilli seeds warehouse, Andhra Pradesh, were cloned and sequenced. The gene from SK-758 (NCBI GenBank accession No. GQ866915) was novel, while that from SK-793 (NCBI GenBank accession No. GQ866914) was identical to the cry2Ab1 gene. The Bacillus thuringiensis Nomenclature Committee ( http://www.lifesci.sussex.ac.uk/home/Neil_Crickmore/Bt/toxins2.html ) named these genes cry2Af2 and cry2Ab16, respectively. The cry2Af2 gene was expressed in Escherichia coli and found to be toxic towards Helicoverpa armigera. The cry2Af2 gene will be useful for pyramiding in transgenic crops.

  8. Effects of Physical (In)activity on Platelet Function

    PubMed Central

    Heber, Stefan; Volf, Ivo

    2015-01-01

    As platelet activation is closely related to the liberation of growth factors and inflammatory mediators, platelets play a central role in the development of CVD. Virtually all cardiovascular risk factors favor platelet hyperreactivity and, accordingly, also physical (in)activity affects platelet function. Within this paper, we will summarize and discuss the current knowledge on the impact of acute and habitual exercise on platelet function. Although there are apparent discrepancies regarding the reported effects of acute, strenuous exercise on platelet activation, a deeper analysis of the available literature reveals that the applied exercise intensity and the subjects' cardiorespiratory fitness represent critical determinants for the observed effects. Consideration of these factors leads to the summary that (i) acute, strenuous exercise can lead to platelet activation, (ii) regular physical activity and/or physical fitness diminish or prevent platelet activation in response to acute exercise, and (iii) habitual physical activity and/or physical fitness also favorably modulate platelet function at physical rest. Notably, these effects of exercise on platelet function show obvious similarities to the well-recognized relation between exercise and the risk for cardiovascular events where vigorous exercise transiently increases the risk for myocardial infarction and a physically active lifestyle dramatically reduces cardiovascular mortality. PMID:26557653

  9. Functional toxicology: a new approach to detect biologically active xenobiotics.

    PubMed Central

    McLachlan, J A

    1993-01-01

    The pervasiveness of chemicals in the environment with estrogenic activity and other biological functions recommends the development of new approaches to monitor and study them. Chemicals can be screened for activity in vitro using a panel of human or animal cells that have been transfected with a specific receptor and reporter gene; for example, the estrogen receptor. By using a variety of different receptors, the screening of xenobiotics for biological functions can be broad. Chemicals could then be classified by their function in vitro which, in some cases, may be a useful guide for toxicological studies. Images Figure 1. PMID:8119246

  10. Models of neural networks with fuzzy activation functions

    NASA Astrophysics Data System (ADS)

    Nguyen, A. T.; Korikov, A. M.

    2017-02-01

    This paper investigates the application of a new form of neuron activation functions that are based on the fuzzy membership functions derived from the theory of fuzzy systems. On the basis of the results regarding neuron models with fuzzy activation functions, we created the models of fuzzy-neural networks. These fuzzy-neural network models differ from conventional networks that employ the fuzzy inference systems using the methods of neural networks. While conventional fuzzy-neural networks belong to the first type, fuzzy-neural networks proposed here are defined as the second-type models. The simulation results show that the proposed second-type model can successfully solve the problem of the property prediction for time – dependent signals. Neural networks with fuzzy impulse activation functions can be widely applied in many fields of science, technology and mechanical engineering to solve the problems of classification, prediction, approximation, etc.

  11. Effects of physical activity on exercise tests and respiratory function

    PubMed Central

    Cheng, Y; Macera, C; Addy, C; Sy, F; Wieland, D; Blair, S

    2003-01-01

    Background: Exercise is an important component of pulmonary rehabilitation for patients with chronic lung disease. Objective: To explore the role of physical activity in maintaining cardiac and respiratory function in healthy people. Methods: Cardiorespiratory fitness was measured by a maximal treadmill test (MTT), and respiratory function was tested by spirometry. The cross sectional study included data from 24 536 healthy persons who were examined at the Cooper Clinic between 1971 and 1995; the longitudinal study included data from 5707 healthy persons who had an initial visit between 1971 and 1995 and a subsequent visit during the next five years. All participants were aged 25–55 years and completed a cardiorespiratory test and a medical questionnaire. Results: In the cross sectional study, after controlling for covariates, being active and not being a recent smoker were associated with better cardiorespiratory fitness and respiratory function in both men and women. In the follow up study, persons who remained or became active had better MTT than persons who remained or became sedentary. Men who remained active had higher forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) than the other groups. Smoking was related to lower cardiorespiratory fitness and respiratory function. Conclusions: Physical activity and non-smoking or smoking cessation is associated with maintenance of cardiorespiratory fitness. Change in physical activity habits is associated with change in cardiorespiratory fitness, but respiratory function contributed little to this association during a five year follow up. PMID:14665592

  12. Heterodimeric interaction between retinoid X receptor alpha and orphan nuclear receptor OR1 reveals dimerization-induced activation as a novel mechanism of nuclear receptor activation.

    PubMed Central

    Wiebel, F F; Gustafsson, J A

    1997-01-01

    OR1 is a member of the steroid/thyroid hormone nuclear receptor superfamily which has been described to mediate transcriptional responses to retinoids and oxysterols. On a DR4 response element, an OR1 heterodimer with the nuclear receptor retinoid X receptor alpha (RXR alpha) has been described to convey transcriptional activation in both the absence and presence of the RXR ligand 9-cis retinoic acid, the mechanisms of which have remained unclear. Here, we dissect the effects of RXR alpha and OR1 ligand-binding domain interaction on transcriptional regulation and the role of the respective carboxy-terminal activation domains (AF-2s) in the absence and presence of the RXR ligand, employing chimeras of the nuclear receptors containing the heterologous GAL4 DNA-binding domain as well as natural receptors. The results show that the interaction of the RXR and OR1 ligand-binding domains unleashes a transcription activation potential that is mainly dependent on the AF-2 of OR1, indicating that interaction with RXR activates OR1. This defines dimerization-induced activation as a novel function of heterodimeric interaction and mechanism of receptor activation not previously described for nuclear receptors. Moreover, we present evidence that activation of OR1 occurs by a conformational change induced upon heterodimerization with RXR. PMID:9199332

  13. Ultrananocrystalline diamond thin films functionalized with therapeutically active collagen networks.

    SciTech Connect

    Huang, H.; Chen, M.; Bruno, P.; Lam, R.; Robinson, E.; Gruen, D.; Ho, D.; Materials Science Division; Northwestern Univ.

    2009-01-01

    The fabrication of biologically amenable interfaces in medicine bridges translational technologies with their surrounding biological environment. Functionalized nanomaterials catalyze this coalescence through the creation of biomimetic and active substrates upon which a spectrum of therapeutic elements can be delivered to adherent cells to address biomolecular processes in cancer, inflammation, etc. Here, we demonstrate the robust functionalization of ultrananocrystalline diamond (UNCD) with type I collagen and dexamethasone (Dex), an anti-inflammatory drug, to fabricate a hybrid therapeutically active substrate for localized drug delivery. UNCD oxidation coupled with a pH-mediated collagen adsorption process generated a comprehensive interface between the two materials, and subsequent Dex integration, activity, and elution were confirmed through inflammatory gene expression assays. These studies confer a translational relevance to the biofunctionalized UNCD in its role as an active therapeutic network for potent regulation of cellular activity toward applications in nanomedicine.

  14. Berberine improves kidney function in diabetic mice via AMPK activation.

    PubMed

    Zhao, Long; Sun, Li-Na; Nie, Hui-Bin; Wang, Xue-Ling; Guan, Guang-Ju

    2014-01-01

    Diabetic nephropathy is a major cause of morbidity and mortality in diabetic patients. Effective therapies to prevent the development of this disease are required. Berberine (BBR) has several preventive effects on diabetes and its complications. However, the molecular mechanism of BBR on kidney function in diabetes is not well defined. Here, we reported that activation of AMP-activated protein kinase (AMPK) is required for BBR-induced improvement of kidney function in vivo. AMPK phosphorylation and activity, productions of reactive oxygen species (ROS), kidney function including serum blood urea nitrogen (BUN), creatinine clearance (Ccr), and urinary protein excretion, morphology of glomerulus were determined in vitro or in vivo. Exposure of cultured human glomerulus mesangial cells (HGMCs) to BBR time- or dose-dependently activates AMPK by increasing the thr172 phosphorylation and its activities. Inhibition of LKB1 by siRNA or mutant abolished BBR-induced AMPK activation. Incubation of cells with high glucose (HG, 30 mM) markedly induced the oxidative stress of HGMCs, which were abolished by 5-aminoimidazole-4-carboxamide ribonucleoside, AMPK gene overexpression or BBR. Importantly, the effects induced by BBR were bypassed by AMPK siRNA transfection in HG-treated HGMCs. In animal studies, streptozotocin-induced hyperglycemia dramatically promoted glomerulosclerosis and impaired kidney function by increasing serum BUN, urinary protein excretion, and decreasing Ccr, as well as increased oxidative stress. Administration of BBR remarkably improved kidney function in wildtype mice but not in AMPKα2-deficient mice. We conclude that AMPK activation is required for BBR to improve kidney function in diabetic mice.

  15. Swell activated chloride channel function in human neutrophils

    SciTech Connect

    Salmon, Michael D.; Ahluwalia, Jatinder

    2009-04-17

    Non-excitable cells such as neutrophil granulocytes are the archetypal inflammatory immune cell involved in critical functions of the innate immune system. The electron current generated (I{sub e}) by the neutrophil NADPH oxidase is electrogenic and rapidly depolarises the membrane potential. For continuous function of the NADPH oxidase, I{sub e} has to be balanced to preserve electroneutrality, if not; sufficient depolarisation would prevent electrons from leaving the cell and neutrophil function would be abrogated. Subsequently, the depolarisation generated by the neutrophil NADPH oxidase I{sub e} must be counteracted by ion transport. The finding that depolarisation required counter-ions to compensate electron transport was followed by the observation that chloride channels activated by swell can counteract the NADPH oxidase membrane depolarisation. In this mini review, we discuss the research findings that revealed the essential role of swell activated chloride channels in human neutrophil function.

  16. Synchronization-based approach for detecting functional activation of brain

    NASA Astrophysics Data System (ADS)

    Hong, Lei; Cai, Shi-Min; Zhang, Jie; Zhuo, Zhao; Fu, Zhong-Qian; Zhou, Pei-Ling

    2012-09-01

    In this paper, we investigate a synchronization-based, data-driven clustering approach for the analysis of functional magnetic resonance imaging (fMRI) data, and specifically for detecting functional activation from fMRI data. We first define a new measure of similarity between all pairs of data points (i.e., time series of voxels) integrating both complete phase synchronization and amplitude correlation. These pairwise similarities are taken as the coupling between a set of Kuramoto oscillators, which in turn evolve according to a nearest-neighbor rule. As the network evolves, similar data points naturally synchronize with each other, and distinct clusters will emerge. The clustering behavior of the interaction network of the coupled oscillators, therefore, mirrors the clustering property of the original multiple time series. The clustered regions whose cross-correlation coefficients are much greater than other regions are considered as the functionally activated brain regions. The analysis of fMRI data in auditory and visual areas shows that the recognized brain functional activations are in complete correspondence with those from the general linear model of statistical parametric mapping, but with a significantly lower time complexity. We further compare our results with those from traditional K-means approach, and find that our new clustering approach can distinguish between different response patterns more accurately and efficiently than the K-means approach, and therefore more suitable in detecting functional activation from event-related experimental fMRI data.

  17. Dipeptides Increase Functional Activity of Human Skin Fibroblasts.

    PubMed

    Malinin, V V; Durnova, A O; Polyakova, V O; Kvetnoi, I M

    2015-05-01

    We analyzed the effect of dipeptide Glu-Trp and isovaleroyl-Glu-Trp in concentrations of 0.2, 2 and 20 μg/ml and Actovegin preparation on functional activity of human skin fibroblasts. Dipeptides, especially Glu-Trp, produce a stimulating effect on human skin fibroblasts and their effect is equivalent to that of Actovegin. Dipeptides stimulate cell renewal processes by activating synthesis of Ki-67 and reducing expression of caspase-9 and enhance antioxidant function of the cells by stimulating the expression of Hsp-90 and inducible NO-synthase. These findings suggest that dipeptides are promising candidates for preparations stimulating reparative processes.

  18. Informational Complexity and Functional Activity of RNA Structures

    PubMed Central

    Carothers, James M.; Oestreich, Stephanie C.; Davis, Jonathan H.

    2004-01-01

    Very little is known about the distribution of functional DNA, RNA, and protein molecules in sequence space. The question of how the number and complexity of distinct solutions to a particular biochemical problem varies with activity is an important aspect of this general problem. Here we present a comparison of the structures and activities of eleven distinct GTP-binding RNAs (aptamers). By experimentally measuring the amount of information required to specify each optimal binding structure, we show that defining a structure capable of 10-fold tighter binding requires approximately 10 additional bits of information. This increase in information content is equivalent to specifying the identity of five additional nucleotide positions and corresponds to an ∼1000-fold decrease in abundance in a sample of random sequences. We observe a similar relationship between structural complexity and activity in a comparison of two catalytic RNAs (ribozyme ligases), raising the possibility of a general relationship between the complexity of RNA structures and their functional activity. Describing how information varies with activity in other heteropolymers, both biological and synthetic, may lead to an objective means of comparing their functional properties. This approach could be useful in predicting the functional utility of novel heteropolymers. PMID:15099096

  19. Self-efficacy: Implications for Physical Activity, Function, and Functional Limitations in Older Adults

    PubMed Central

    McAuley, Edward; Szabo, Amanda; Gothe, Neha; Olson, Erin A.

    2013-01-01

    Attenuating the physical decline and increases in disability associated with the aging process is an important public health priority. Evidence suggests that regular physical activity participation improves functional performance, such as walking, standing balance, flexibility, and getting up out of a chair, and also plays an important role in the disablement process by providing a protective effect against functional limitations. Whether these effects are direct or indirect has yet to be reliably established. In this review, the authors take the perspective that such relationships are indirect and operate through self-efficacy expectations. They first provide an introduction to social cognitive theory followed by an overview of self-efficacy's reciprocal relationship with physical activity. They then consider the literature that documents the effects of physical activity on functional performance and functional limitations in older adults and the extent to which self-efficacy might mediate these relationships. Furthermore, they also present evidence that suggests that self-efficacy plays a pivotal role in a model in which the protective effects conferred by physical activity on functional limitations operate through functional performance. The article concludes with a brief section making recommendations for the development of strategies within physical activity and rehabilitative programs for maximizing the major sources of efficacy information. PMID:24353482

  20. Functional modifications of macrophage activity after sublethal irradiation. [Toxoplasma gondii

    SciTech Connect

    Swartz, R.P.

    1982-01-01

    The modifications of macrophage activity following sublethal irradiation, both in vivo and in vitro, were studied using spreading and C3b-receptor-mediated ingestion assays. Nonelicited peritoneal washout cells were examined for changes in activity and selected population characteristics. The cells from irradiated mice were from a resident peritoneal population and not immigrating cells. The macrophage population showed enhanced activity early with a refractory period (24-48) when the macrophages were unresponsive to stimulation by irradiated lymphocytes. The enhanced activity was inversely dose dependent on macrophage. The lymphocytes showed a regulatory function(s) on the time post irradiation at which they were examined. Early lymphocytes exhibited the ability to enhance the activity of normal macrophages while lymphocytes removed 24 hours post irradiation could suppress the activity of already activated macrophages. The effect(s) of the various lymphocyte populations were reproduced with cell-free supernatants which was indicative of the production of lymphokines. Separation on nylon wool columns indicated that the activity resided primarily in the T-cell population of lymphocytes. In vitro irradiation indicated that stimulation of the lymphocytes is macrophage dependent. Additional work indicated that sublethally irradiated macrophages did not inhibit replication of the coccidian protozoon Toxoplasma gondii although they did show increased phagocytosis. Examination of the serum from whole body irradiated mice showed the presence of a postirradiation substance which enhanced the phagocytosis of normal macrophages. It was not present in the serum of normal mice and was not endotoxin.

  1. Functional Embedding Predicts the Variability of Neural Activity

    PubMed Central

    Mišić, Bratislav; Vakorin, Vasily A.; Paus, Tomáš; McIntosh, Anthony R.

    2011-01-01

    Neural activity is irregular and unpredictable, yet little is known about why this is the case and how this property relates to the functional architecture of the brain. Here we show that the variability of a region’s activity systematically varies according to its topological role in functional networks. We recorded the resting-state electroencephalogram (EEG) and constructed undirected graphs of functional networks. We measured the centrality of each node in terms of the number of connections it makes (degree), the ease with which the node can be reached from other nodes in the network (efficiency) and the tendency of the node to occupy a position on the shortest paths between other pairs of nodes in the network (betweenness). As a proxy for variability, we estimated the information content of neural activity using multiscale entropy analysis. We found that the rate at which information was generated was largely predicted by centrality. Namely, nodes with greater degree, betweenness, and efficiency were more likely to have high information content, while peripheral nodes had relatively low information content. These results suggest that the variability of regional activity reflects functional embedding. PMID:22164135

  2. The restless brain: how intrinsic activity organizes brain function.

    PubMed

    Raichle, Marcus E

    2015-05-19

    Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease.

  3. The restless brain: how intrinsic activity organizes brain function

    PubMed Central

    Raichle, Marcus E.

    2015-01-01

    Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease. PMID:25823869

  4. Heated Proteins are Still Active in a Functionalized Nanoporous Support

    SciTech Connect

    Chen, Baowei; Qi, Wen N.; Li, Xiaolin; Lei, Chenghong; Liu, Jun

    2013-07-08

    We report that even under the heated condition, the conformation and activity of a protein can be hoarded in a functionalized nanoporous support via non-covalent interaction, although the hoarded protein was not exhibiting the full protein activity, the protein released subsequently still maintained its native conformation and activity. Glucose oxidase (GOX) was spontaneously and largely entrapped in aminopropyl-functionalized mesoporous silica (NH2-FMS) at 20 oC via a dominant electrostatic interaction. Although FMS-GOX displayed 45% activity of the free enzyme in solution, the GOX released from FMS exhibited its 100% activity prior to the entrapment. Surprisingly, the released GOX from FMS still maintained 89% of its initial activity prior to the entrapment after FMS-GOX was incubated at 60 oC for 1 h prior to release, while the free GOX in solution lost nearly all activity under the same incubation. Intrinsic fluorescence emission of GOX and native electrophoresis demonstrated that the heating resulted in significant conformational changes and oligomeric structures of the free GOX, but FMS efficiently maintained the thermal stability of GOX therein and resisted the thermal denaturation and oligomeric aggregation.

  5. Multi-neuronal activity and functional connectivity in cell assemblies.

    PubMed

    Roudi, Yasser; Dunn, Benjamin; Hertz, John

    2015-06-01

    Our ability to collect large amounts of data from many cells has been paralleled by the development of powerful statistical models for extracting information from this data. Here we discuss how the activity of cell assemblies can be analyzed using these models, focusing on the generalized linear models and the maximum entropy models and describing a number of recent studies that employ these tools for analyzing multi-neuronal activity. We show results from simulations comparing inferred functional connectivity, pairwise correlations and the real synaptic connections in simulated networks demonstrating the power of statistical models in inferring functional connectivity. Further development of network reconstruction techniques based on statistical models should lead to more powerful methods of understanding functional anatomy of cell assemblies.

  6. Human brain activity with functional NIR optical imager

    NASA Astrophysics Data System (ADS)

    Luo, Qingming

    2001-08-01

    In this paper we reviewed the applications of functional near infrared optical imager in human brain activity. Optical imaging results of brain activity, including memory for new association, emotional thinking, mental arithmetic, pattern recognition ' where's Waldo?, occipital cortex in visual stimulation, and motor cortex in finger tapping, are demonstrated. It is shown that the NIR optical method opens up new fields of study of the human population, in adults under conditions of simulated or real stress that may have important effects upon functional performance. It makes practical and affordable for large populations the complex technology of measuring brain function. It is portable and low cost. In cognitive tasks subjects could report orally. The temporal resolution could be millisecond or less in theory. NIR method will have good prospects in exploring human brain secret.

  7. Functional modules, structural topology, and optimal activity in metabolic networks.

    PubMed

    Resendis-Antonio, Osbaldo; Hernández, Magdalena; Mora, Yolanda; Encarnación, Sergio

    2012-01-01

    Modular organization in biological networks has been suggested as a natural mechanism by which a cell coordinates its metabolic strategies for evolving and responding to environmental perturbations. To understand how this occurs, there is a need for developing computational schemes that contribute to integration of genomic-scale information and assist investigators in formulating biological hypotheses in a quantitative and systematic fashion. In this work, we combined metabolome data and constraint-based modeling to elucidate the relationships among structural modules, functional organization, and the optimal metabolic phenotype of Rhizobium etli, a bacterium that fixes nitrogen in symbiosis with Phaseolus vulgaris. To experimentally characterize the metabolic phenotype of this microorganism, we obtained the metabolic profile of 220 metabolites at two physiological stages: under free-living conditions, and during nitrogen fixation with P. vulgaris. By integrating these data into a constraint-based model, we built a refined computational platform with the capability to survey the metabolic activity underlying nitrogen fixation in R. etli. Topological analysis of the metabolic reconstruction led us to identify modular structures with functional activities. Consistent with modular activity in metabolism, we found that most of the metabolites experimentally detected in each module simultaneously increased their relative abundances during nitrogen fixation. In this work, we explore the relationships among topology, biological function, and optimal activity in the metabolism of R. etli through an integrative analysis based on modeling and metabolome data. Our findings suggest that the metabolic activity during nitrogen fixation is supported by interacting structural modules that correlate with three functional classifications: nucleic acids, peptides, and lipids. More fundamentally, we supply evidence that such modular organization during functional nitrogen fixation is

  8. Histamine H3 activation depresses cardiac function in experimental sepsis.

    PubMed

    Li, X; Eschun, G; Bose, D; Jacobs, H; Yang, J J; Light, R B; Mink, S N

    1998-11-01

    In the heart, histamine (H3) receptors may function as inhibitory presynaptic receptors that decrease adrenergic norepinephrine release in conditions of enhanced sympathetic neural activity. We hypothesized that H3-receptor blockade might improve cardiovascular function in sepsis. In a canine model of Escherichia coli sepsis, we found that H3-receptor blockade increased cardiac output (3.6 to 5.3 l/min, P < 0.05), systemic blood pressure (mean 76 to 96 mmHg, P < 0.05), and left ventricular contractility compared with pretreatment values. Plasma histamine concentrations increased modestly in the H3-blocker-sepsis group compared with values obtained in a nonsepsis-time-control group. In an in vitro preparation, histamine H3 activation could be identified under conditions of septic plasma. We conclude that activation of H3 receptors may contribute to cardiovascular collapse in sepsis.

  9. Ramiprilate inhibits functional matrix metalloproteinase activity in Crohn's disease fistulas.

    PubMed

    Efsen, Eva; Saermark, Torben; Hansen, Alastair; Bruun, Eywin; Brynskov, Jørn

    2011-09-01

    Increased expression of matrix metalloproteinase (MMP)-2, -3 and -9 has been demonstrated in Crohn's disease fistulas, but it is unknown whether these enzymes are biologically active and represent a therapeutic target. Therefore, we investigated the proteolytic activity of MMPs in fistula tissue and examined the effect of inhibitors, including clinically available drugs that beside their main action also suppress MMPs. Fistula specimens were obtained by surgical excision from 22 patients with Crohn's disease and from 10 patients with fistulas resulting from other causes. Colonic endoscopic biopsies from six controls were also included. Total functional MMP activity was measured by a high-pressure liquid chromatography (HPLC)-based, fluorogenic MMP-substrate cleavage assay, and the specific activity of MMP-2, -3 and -9 by the MMP Biotrak Activity Assay. The MMP inhibitors comprised ethylene-diamine-tetraacetic acid (EDTA), the synthetic broad-spectrum inhibitor, GM6001, the angiotensin-converting enzyme (ACE) inhibitor, ramiprilate, and the tetracycline, doxycycline. In Crohn's disease fistulas, about 50% of the total protease activity was attributable to MMP activity. The average total MMP activity was significantly higher (about 3.5-times) in Crohn's fistulas (471 FU/μg protein, range 49-2661) compared with non-Crohn's fistulas [134 FU/μg protein, range 0-495, (p < 0.05)] and normal colon [153 FU/μg protein, range 77-243, (p < 0.01)]. MMP-3 activity was increased in Crohn's fistulas (1.4 ng/ml, range 0-9.83) compared with non-Crohn's fistulas, [0.32 ng/ml, range 0-2.66, (p < 0.02)]. The same applied to MMP-9 activity [0.64 ng/ml, range 0-5.66 and 0.17 ng/ml, range 0-1.1, respectively (p < 0.04)]. Ramiprilate significantly decreased the average total MMP activity level by 42% and suppressed the specific MMP-3 activity by 72%, which is comparable to the effect of GM6001 (87%). Moreover, MMP-9 activity was completely blunted by ramiprilate. Doxycycline had no

  10. Motivational activation: a unifying hypothesis of orexin/hypocretin function

    PubMed Central

    Mahler, Stephen V; Moorman, David E; Smith, Rachel J; James, Morgan H; Aston-Jones, Gary

    2015-01-01

    Orexins (hypocretins) are two peptides (orexin A and B) produced from the pre-pro-orexin precursor and expressed in a limited region of dorsolateral hypothalamus. Orexins were originally thought to specifically mediate feeding and promote wakefulness, but it is now clear that they participate in a wide range of behavioral and physiological processes under select circumstances. Orexins primarily mediate behavior under situations of high motivational relevance, such as during physiological need states, exposure to threats or reward opportunities. We hypothesize that many behavioral functions of orexins (including regulation of sleep/wake cycling) reflect a fundamentally integrated function for orexins in translating motivational activation into organized suites of psychological and physiological processes supporting adaptive behaviors. We also discuss how numerous forms of neural heterogeneity modulate this function, allowing orexin neurons to organize diverse, adaptive responses in a variety of motivationally relevant situations. Thus, the involvement of orexins in diverse behaviors may reflect a common underlying function for this peptide system. PMID:25254979

  11. Serotonin and Dopamine: Unifying Affective, Activational, and Decision Functions

    PubMed Central

    Cools, Roshan; Nakamura, Kae; Daw, Nathaniel D

    2011-01-01

    Serotonin, like dopamine (DA), has long been implicated in adaptive behavior, including decision making and reinforcement learning. However, although the two neuromodulators are tightly related and have a similar degree of functional importance, compared with DA, we have a much less specific understanding about the mechanisms by which serotonin affects behavior. Here, we draw on recent work on computational models of dopaminergic function to suggest a framework by which many of the seemingly diverse functions associated with both DA and serotonin—comprising both affective and activational ones, as well as a number of other functions not overtly related to either—can be seen as consequences of a single root mechanism. PMID:20736991

  12. Motivational activation: a unifying hypothesis of orexin/hypocretin function.

    PubMed

    Mahler, Stephen V; Moorman, David E; Smith, Rachel J; James, Morgan H; Aston-Jones, Gary

    2014-10-01

    Orexins (hypocretins) are two peptides (orexin A and B) produced from the pre-pro-orexin precursor and expressed in a limited region of dorsolateral hypothalamus. Orexins were originally thought to specifically mediate feeding and promote wakefulness, but it is now clear that they participate in a wide range of behavioral and physiological processes under select circumstances. Orexins primarily mediate behavior under situations of high motivational relevance, such as during physiological need states, exposure to threats or reward opportunities. We hypothesize that many behavioral functions of orexins (including regulation of sleep/wake cycling) reflect a fundamentally integrated function for orexins in translating motivational activation into organized suites of psychological and physiological processes supporting adaptive behaviors. We also discuss how numerous forms of neural heterogeneity modulate this function, allowing orexin neurons to organize diverse, adaptive responses in a variety of motivationally relevant situations. Thus, the involvement of orexins in diverse behaviors may reflect a common underlying function for this peptide system.

  13. Physical activity and memory functions: an interventional study.

    PubMed

    Ruscheweyh, R; Willemer, C; Krüger, K; Duning, T; Warnecke, T; Sommer, J; Völker, K; Ho, H V; Mooren, F; Knecht, S; Flöel, A

    2011-07-01

    Previous studies have suggested beneficial effects of physical activity on cognition. Here, we asked in an interventional approach if physical activity performed at different intensity levels would differentially affect episodic memory function. Additionally, we tried to identify mechanisms mediating these changes. Sixty-two healthy elderly individuals were assessed for level of physical activity, aerobic fitness, episodic memory score, neurotrophin and catecholamine levels, and received a magnetic resonance image of the brain at baseline and after a six months intervention of medium or low-intensity physical activity or control. Increase in total physical activity was positively associated with increase in memory score over the entire cohort, without significant differences between intensity groups. It was also positively associated with increases in local gray matter volume in prefrontal and cingulate cortex, and BDNF levels (trend). In conclusion, we showed that physical activity conveys the beneficial effects on memory function independently of its intensity, possibly mediated by local gray matter volume and neurotrophic factors. Our findings may carry significant implications for prevention of cognitive decline in the elderly.

  14. Antioxidant Activities of Functional Beverage Concentrates Containing Herbal Medicine Extracts

    PubMed Central

    Park, Seon-Joo; Kim, Mi-Ok; Kim, Jung Hoan; Jeong, Sehyun; Kim, Min Hee; Yang, Su-Jin; Lee, Jongsung; Lee, Hae-Jeung

    2017-01-01

    This study investigated the antioxidant activity of functional beverage concentrates containing herbal medicine extracts (FBCH) using various antioxidant assays, such as 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity, and reducing power assay. The total polyphenolic content of FBCH (81.45 mg/100 g) was higher than Ssanghwa tea (SHT, 37.56 mg/100 g). The antioxidant activities of FBCH showed 52.92% DPPH and 55.18% ABTS radical scavenging activities at 100 mg/mL, respectively. FBCH showed significantly higher antioxidant activities compared to the SHT (DPPH, 23.43%; ABTS, 22.21%; reducing power optical density; 0.23, P<0.05). In addition, intracellular reactive oxygen species generation significantly decreased in a concentration-dependent manner following FBCH treatment. These results suggest that the addition of herbal medicine extract contributes to the improved functionality of beverage concentrates.

  15. Self-assembly of active colloidal molecules with dynamic function

    NASA Astrophysics Data System (ADS)

    Soto, Rodrigo; Golestanian, Ramin

    Catalytically active colloids maintain non-equilibrium conditions in which they produce and deplete chemicals at their surface. While individual colloids that are symmetrically coated do not exhibit dynamical activity, the concentration fields resulting from their chemical activity decay as 1/r and produce gradients that attract or repel other colloids depending on their surface chemistry and ambient variables. This results in a non-equilibrium analogue of ionic systems, but with the remarkable novel feature of action-reaction symmetry breaking. In dilute conditions these active colloids join up to form molecules via generalized ionic bonds. Colloids are found to join up to form self-assembled molecules that could be inert or have spontaneous activity in the form of net translational velocity and spin depending on their symmetry properties and their constituents. As the interactions do not satisfy detailed-balance, it is possible to achieve structures with time dependent functionality. We study a molecule that adopts spontaneous oscillations and another that exhibits a run-and-tumble dynamics similar to bacteria. Our study shows that catalytically active colloids could be used for designing self-assembled structures that posses dynamical functionalities.

  16. Chemical Signaling and Functional Activation in Colloidosome-Based Protocells.

    PubMed

    Sun, Shiyong; Li, Mei; Dong, Faqin; Wang, Shengjie; Tian, Liangfei; Mann, Stephen

    2016-04-13

    An aqueous-based microcompartmentalized model involving the integration of partially hydrophobic Fe(III)-rich montmorillonite (FeM) clay particles as structural and catalytic building blocks for colloidosome membrane assembly, self-directed membrane remodeling, and signal-induced protocell communication is described. The clay colloidosomes exhibit size- and charge-selective permeability, and show dual catalytic functions involving spatially confined enzyme-mediated dephosphorylation and peroxidase-like membrane activity. The latter is used for the colloidosome-mediated synthesis and assembly of a temperature-responsive poly(N-isopropylacrylamide)(PNIPAM)/clay-integrated hybrid membrane. In situ PNIPAM elaboration of the membrane is coupled to a glucose oxidase (GOx)-mediated signaling pathway to establish a primitive model of chemical communication and functional activation within a synthetic "protocell community" comprising a mixed population of GOx-containing silica colloidosomes and alkaline phosphatase (ALP)-containing FeM-clay colloidosomes. Triggering the enzyme reaction in the silica colloidosomes gives a hydrogen peroxide signal that induces polymer wall formation in a coexistent population of the FeM-clay colloidosomes, which in turn generates self-regulated membrane-gated ALP-activity within the clay microcompartments. The emergence of new functionalities in inorganic colloidosomes via chemical communication between different protocell populations provides a first step toward the realization of interacting communities of synthetic functional microcompartments.

  17. Function and biotechnology of extremophilic enzymes in low water activity

    PubMed Central

    2012-01-01

    Enzymes from extremophilic microorganisms usually catalyze chemical reactions in non-standard conditions. Such conditions promote aggregation, precipitation, and denaturation, reducing the activity of most non-extremophilic enzymes, frequently due to the absence of sufficient hydration. Some extremophilic enzymes maintain a tight hydration shell and remain active in solution even when liquid water is limiting, e.g. in the presence of high ionic concentrations, or at cold temperature when water is close to the freezing point. Extremophilic enzymes are able to compete for hydration via alterations especially to their surface through greater surface charges and increased molecular motion. These properties have enabled some extremophilic enzymes to function in the presence of non-aqueous organic solvents, with potential for design of useful catalysts. In this review, we summarize the current state of knowledge of extremophilic enzymes functioning in high salinity and cold temperatures, focusing on their strategy for function at low water activity. We discuss how the understanding of extremophilic enzyme function is leading to the design of a new generation of enzyme catalysts and their applications to biotechnology. PMID:22480329

  18. XIAP reverses various functional activities of FRNK in endothelial cells

    SciTech Connect

    Ahn, Sunyoung; Kim, Hyun Jeong; Chi, Sung-Gil; Park, Heonyong

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer FRNK domain is recruited into focal adhesion (FA), controlling endothelial cell adhesion. Black-Right-Pointing-Pointer XIAP binds the FRNK domain of FAK. Black-Right-Pointing-Pointer XIAP inhibits recruitment of FRNK into Fas and FRNK-promoted cell adhesion. Black-Right-Pointing-Pointer XIAP plays a key role in vascular functions of FRNK or FRNK domain-mediated vascular functions of FAK. -- Abstract: In endothelial cells, focal adhesion kinase (FAK) regulates cell proliferation, migration, adhesion, and shear-stimulated activation of MAPK. We recently found that FAK is recruited into focal adhesion (FA) sites through interactions with XIAP (X-chromosome linked inhibitor of apoptosis protein) and activated by Src kinase in response to shear stress. In this study, we examined which domain(s) of FAK is(are) important for various vascular functions such as FA recruiting, XIAP-binding and shear stress-stimulated ERK activation. Through a series of experiments, we determined that the FRNK domain is recruited into FA sites and promotes endothelial cell adhesion. Interestingly, XIAP knockdown was shown to reduce FA recruitment of FRNK and the cell adhesive effect of FRNK. In addition, we found that XIAP interacts with FRNK, suggesting cross-talk between XIAP and FRNK. We also demonstrated that FRNK inhibits endothelial cell migration and shear-stimulated ERK activation. These inhibitory effects of FRNK were reversed by XIAP knockdown. Taken together, we can conclude that XIAP plays a key role in vascular functions of FRNK or FRNK domain-mediated vascular functions of FAK.

  19. EGFR regulates macrophage activation and function in bacterial infection.

    PubMed

    Hardbower, Dana M; Singh, Kshipra; Asim, Mohammad; Verriere, Thomas G; Olivares-Villagómez, Danyvid; Barry, Daniel P; Allaman, Margaret M; Washington, M Kay; Peek, Richard M; Piazuelo, M Blanca; Wilson, Keith T

    2016-09-01

    EGFR signaling regulates macrophage function, but its role in bacterial infection has not been investigated. Here, we assessed the role of macrophage EGFR signaling during infection with Helicobacter pylori, a bacterial pathogen that causes persistent inflammation and gastric cancer. EGFR was phosphorylated in murine and human macrophages during H. pylori infection. In human gastric tissues, elevated levels of phosphorylated EGFR were observed throughout the histologic cascade from gastritis to carcinoma. Deleting Egfr in myeloid cells attenuated gastritis and increased H. pylori burden in infected mice. EGFR deficiency also led to a global defect in macrophage activation that was associated with decreased cytokine, chemokine, and NO production. We observed similar alterations in macrophage activation and disease phenotype in the Citrobacter rodentium model of murine infectious colitis. Mechanistically, EGFR signaling activated NF-κB and MAPK1/3 pathways to induce cytokine production and macrophage activation. Although deletion of Egfr had no effect on DC function, EGFR-deficient macrophages displayed impaired Th1 and Th17 adaptive immune responses to H. pylori, which contributed to decreased chronic inflammation in infected mice. Together, these results indicate that EGFR signaling is central to macrophage function in response to enteric bacterial pathogens and is a potential therapeutic target for infection-induced inflammation and associated carcinogenesis.

  20. Aldehyde dehydrogenase 2 activation in heart failure restores mitochondrial function and improves ventricular function and remodelling

    PubMed Central

    Gomes, Katia M.S.; Campos, Juliane C.; Bechara, Luiz R.G.; Queliconi, Bruno; Lima, Vanessa M.; Disatnik, Marie-Helene; Magno, Paulo; Chen, Che-Hong; Brum, Patricia C.; Kowaltowski, Alicia J.; Mochly-Rosen, Daria; Ferreira, Julio C.B.

    2014-01-01

    Aims We previously demonstrated that pharmacological activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) protects the heart against acute ischaemia/reperfusion injury. Here, we determined the benefits of chronic activation of ALDH2 on the progression of heart failure (HF) using a post-myocardial infarction model. Methods and results We showed that a 6-week treatment of myocardial infarction-induced HF rats with a selective ALDH2 activator (Alda-1), starting 4 weeks after myocardial infarction at a time when ventricular remodelling and cardiac dysfunction were present, improved cardiomyocyte shortening, cardiac function, left ventricular compliance and diastolic function under basal conditions, and after isoproterenol stimulation. Importantly, sustained Alda-1 treatment showed no toxicity and promoted a cardiac anti-remodelling effect by suppressing myocardial hypertrophy and fibrosis. Moreover, accumulation of 4-hydroxynonenal (4-HNE)-protein adducts and protein carbonyls seen in HF was not observed in Alda-1-treated rats, suggesting that increasing the activity of ALDH2 contributes to the reduction of aldehydic load in failing hearts. ALDH2 activation was associated with improved mitochondrial function, including elevated mitochondrial respiratory control ratios and reduced H2O2 release. Importantly, selective ALDH2 activation decreased mitochondrial Ca2+-induced permeability transition and cytochrome c release in failing hearts. Further supporting a mitochondrial mechanism for ALDH2, Alda-1 treatment preserved mitochondrial function upon in vitro aldehydic load. Conclusions Selective activation of mitochondrial ALDH2 is sufficient to improve the HF outcome by reducing the toxic effects of aldehydic overload on mitochondrial bioenergetics and reactive oxygen species generation, suggesting that ALDH2 activators, such as Alda-1, have a potential therapeutic value for treating HF patients. PMID:24817685

  1. β-Glucans: Relationships between Modification, Conformation and Functional Activities.

    PubMed

    Wang, Qiang; Sheng, Xiaojing; Shi, Aimin; Hu, Hui; Yang, Ying; Liu, Li; Fei, Ling; Liu, Hongzhi

    2017-02-09

    β-glucan is a type of polysaccharide which widely exists in bacteria, fungi, algae, and plants, and has been well known for its biological activities such as enhancing immunity, antitumor, antibacterial, antiviral, and wound healing activities. The conformation of β-glucan plays a crucial role on its biological activities. Therefore, β-glucans obtained from different sources, while sharing the same basic structures, often show different bioactivities. The basic structure and inter-molecular forces of polysaccharides can be changed by modification, which leads to the conformational transformation in solution that can directly affect bioactivity. In this review, we will first determine different ways to modify β-glucan molecules including physical methods, chemical methods, and biological methods, and then reveal the relationship of the flexible helix form of the molecule chain and the helix conformation to their bioactivities. Last, we summarize the scientific challenges to modifying β-glucan's conformation and functional activity, and discuss its potential future development.

  2. Active Acetylcholinesterase Immobilization on a Functionalized Silicon Surface.

    PubMed

    Khaldi, K; Sam, S; Gouget-Laemmel, A C; Henry de Villeneuve, C; Moraillon, A; Ozanam, F; Yang, J; Kermad, A; Ghellai, N; Gabouze, N

    2015-08-04

    In this work, we studied the attachment of active acetylcholinesterase (AChE) enzyme on a silicon substrate as a potential biomarker for the detection of organophosphorous (OP) pesticides. A multistep functionalization strategy was developed on a crystalline silicon surface: a carboxylic acid-terminated monolayer was grafted onto a hydrogen-terminated silicon surface by photochemical hydrosilylation, and then AChE was covalently attached through amide bonds using an activation EDC/NHS process. Each step of the modification was quantitatively characterized by ex-situ Fourier transform infrared spectroscopy in attenuated-total-reflection geometry (ATR-FTIR) and atomic force microscopy (AFM). The kinetics of enzyme immobilization was investigated using in situ real-time infrared spectroscopy. The enzymatic activity of immobilized acetylcholinesterase enzymes was determined with a colorimetric test. The surface concentration of active AChE was estimated to be Γ = 1.72 × 10(10) cm(-2).

  3. Muscle metabolic function and free-living physical activity.

    PubMed

    Hunter, Gary R; Larson-Meyer, D Enette; Sirikul, Bovorn; Newcomer, Bradley R

    2006-11-01

    We have previously shown that muscle metabolic function measured during exercise is related to exercise performance and subsequent 1-yr weight gain. Because it is well established that physical activity is important in weight maintenance, we examined muscle function relationships with free-living energy expenditure and physical activity. Subjects were 71 premenopausal black and white women. Muscle metabolism was evaluated by (31)P magnetic resonance spectroscopy during 90-s isometric plantar flexion contractions (45% maximum). Free-living energy expenditure (TEE) was measured using doubly labeled water, activity-related energy expenditure (AEE) was calculated as 0.9 x TEE - sleeping energy expenditure from room calorimetry, and free-living physical activity (ARTE) was calculated by dividing AEE by energy cost of standard physical activities. At the end of exercise, anaerobic glycolytic rate (ANGLY) and muscle concentration of phosphomonoesters (PME) were negatively related to TEE, AEE, and ARTE (P < 0.05). Multiple regression analysis showed that both PME (partial r = -0.29, <0.02) and ANGLY (partial r = -0.24, P < 0.04) were independently related to ARTE. PME, primarily glucose-6-phosphate and fructose-6-phosphate, was significantly related to ratings of perceived exertion (r = 0.21, P < or = 0.05) during a maximal treadmill test. PME was not related to ARTE after inclusion of RPE in the multiple regression model, suggesting that PME may be obtaining its relationship with ARTE through an increased perception of effort during physical activity. In conclusion, physically inactive individuals tend to be more dependent on anaerobic glycolysis during exercise while relying on a glycolytic pathway that may not be functioning optimally.

  4. Review: Production and functionality of active peptides from milk.

    PubMed

    Muro Urista, C; Álvarez Fernández, R; Riera Rodriguez, F; Arana Cuenca, A; Téllez Jurado, A

    2011-08-01

    In recent years, research on the production of active peptides obtained from milk and their potential functionality has grown, to a great extent. Bioactive peptides have been defined as specific protein fragments that have a positive impact on body functions or conditions, and they may ultimately have an influence on health. Individual proteins of casein or milk-derived products such as cheese and yogurt have been used as a protein source to study the isolation and activity of peptides with several applications. Currently, the milk whey waste obtained in the production of cheese also represents a protein source from which active peptides could be isolated with potential industrial applications. The active properties of milk peptides and the results found with regard to their physiological effects have led to the classification of peptides as belonging to the group of ingredients of protein nature, appropriate for use in functional foods or pharmaceutical formulations. In this study, the main peptides obtained from milk protein and the past research studies about its production and biological activities will be explained. Second, an analysis will be made on the methods to determinate the biological activities, the separation of bioactive peptides and its structure identification. All of these form the base required to obtain synthetic peptides. Finally, we explain the experimental animal and human trials done in the past years. Nevertheless, more research is required on the design and implementation of equipment for the industrial production and separation of peptides. In addition, different authors suggest that more emphasis should therefore be given to preclinical studies, proving that results are consistent and that effects are demonstrated repeatedly by several research human groups.

  5. Platelet function, activation and apoptosis during and after apheresis.

    PubMed

    Bakry, Rania; Sayed, Douaa; Galal, Hanan; Shaker, Sanaa

    2010-10-01

    Platelets are known to undergo shape change, activation, release reaction and apoptosis/necrosis during processing and storage. Apheresis may have a deleterious impact on platelet achievability and functional integrity. Platelet concentrates from 50 male volunteers obtained by COBE spectra were screened for platelet activation (CD62 and CD154) and apoptosis (phosphatidylserine detected by Annexin V). Donor samples before separation, during apheresis and at the third day of storage were used as baseline donor samples. Platelet aggregation to adenosine diphosphate (ADP) and collagen was performed. There was a statistically significant increase in the expression of activation markers in two different samples (during separation samples and third day samples). Although the increase in Annexin V expression was not so observable, it showed a significant increase also. There was marked decline in the platelet aggregation. The correlations between the values of CD62, CD154 and Annexin V were detected in baseline samples and increased during separation and at the third day of platelets storage. Correlation between values of platelet aggregation to collagen and Annexin V was relevant only in the baseline samples. No other correlations were encountered between platelet aggregation and markers of activation and apoptosis during apheresis and storage. Initial platelet activation induced by apheresis may have an impact on phosphatidylserine expression with no impact on aggregation function of platelets during storage.

  6. Self-assembly of active colloidal molecules with dynamic function

    NASA Astrophysics Data System (ADS)

    Soto, Rodrigo; Golestanian, Ramin

    2015-05-01

    Catalytically active colloids maintain nonequilibrium conditions in which they produce and deplete chemicals and hence effectively act as sources and sinks of molecules. While individual colloids that are symmetrically coated do not exhibit any form of dynamical activity, the concentration fields resulting from their chemical activity decay as 1 /r and produce gradients that attract or repel other colloids depending on their surface chemistry and ambient variables. This results in a nonequilibrium analog of ionic systems, but with the remarkable novel feature of action-reaction symmetry breaking. We study solutions of such chemically active colloids in dilute conditions when they join up to form molecules via generalized ionic bonds and discuss how we can achieve structures with time-dependent functionality. In particular, we study a molecule that adopts a spontaneous oscillatory pattern of conformations and another that exhibits a run-and-tumble dynamics similar to bacteria. Our study shows that catalytically active colloids could be used for designing self-assembled structures that possess dynamical functionalities that are determined by their prescribed three-dimensional structures, a strategy that follows the design principle of proteins.

  7. SUMOylation of ROR{alpha} potentiates transcriptional activation function

    SciTech Connect

    Hwang, Eun Ju; Lee, Ji Min; Jeong, Jiyeong; Park, Joo Hyeon; Yang, Young; Lim, Jong-Seok; Kim, Jung Hwa; Baek, Sung Hee; Kim, Keun Il

    2009-01-16

    SUMOylation regulates a variety of cellular processes, including control of transcriptional activities of nuclear receptors. Here, we present SUMOylation of orphan nuclear receptor, ROR{alpha} by both SUMO-1 and SUMO-2. SUMOylation of ROR{alpha} occurred on the 240th lysine residue at the hinge region of human protein. PIAS family members, PIASx{alpha}, PIAS3, and PIASy, increased SUMOylation of ROR{alpha}, whereas SENP2 specifically removed SUMO from ROR{alpha}. SUMOylation-defective mutant form of ROR{alpha} exhibited decreased transcriptional activity on ROR{alpha}-responsive promoters indicating that SUMOylation may positively regulate transcriptional function of ROR{alpha}.

  8. Polyhexamethylene biguanide functionalized cationic silver nanoparticles for enhanced antimicrobial activity

    PubMed Central

    2012-01-01

    Polyhexamethylene biguanide (PHMB), a broad spectrum disinfectant against many pathogens, was used as a stabilizing ligand for the synthesis of fairly uniform silver nanoparticles. The particles formed were characterized using UV-visible spectroscopy, FTIR, dynamic light scattering, electrophoretic mobility, and TEM to measure their morphology and surface chemistry. PHMB-functionalized silver nanoparticles were then evaluated for their antimicrobial activity against a gram-negative bacterial strain, Escherichia coli. These silver nanoparticles were found to have about 100 times higher bacteriostatic and bactericidal activities, compared to the previous reports, due to the combined antibacterial effect of silver nanoparticles and PHMB. In addition to other applications, PHMB-functionalized silver nanoparticles would be extremely useful in textile industry due to the strong interaction of PHMB with cellulose fabrics. PMID:22625664

  9. Polyhexamethylene biguanide functionalized cationic silver nanoparticles for enhanced antimicrobial activity

    NASA Astrophysics Data System (ADS)

    Ashraf, Sumaira; Akhtar, Nasrin; Ghauri, Muhammad Afzal; Rajoka, Muhammad Ibrahim; Khalid, Zafar M.; Hussain, Irshad

    2012-05-01

    Polyhexamethylene biguanide (PHMB), a broad spectrum disinfectant against many pathogens, was used as a stabilizing ligand for the synthesis of fairly uniform silver nanoparticles. The particles formed were characterized using UV-visible spectroscopy, FTIR, dynamic light scattering, electrophoretic mobility, and TEM to measure their morphology and surface chemistry. PHMB-functionalized silver nanoparticles were then evaluated for their antimicrobial activity against a gram-negative bacterial strain, Escherichia coli. These silver nanoparticles were found to have about 100 times higher bacteriostatic and bactericidal activities, compared to the previous reports, due to the combined antibacterial effect of silver nanoparticles and PHMB. In addition to other applications, PHMB-functionalized silver nanoparticles would be extremely useful in textile industry due to the strong interaction of PHMB with cellulose fabrics.

  10. Spillover-mediated feedforward-inhibition functionally segregates interneuron activity

    PubMed Central

    Coddington, Luke T.; Rudolph, Stephanie; Lune, Patrick Vande; Overstreet-Wadiche, Linda; Wadiche, Jacques I.

    2013-01-01

    Summary Neurotransmitter spillover represents a form of neural transmission not restricted to morphologically defined synaptic connections. Communication between climbing fibers (CFs) and molecular layer interneurons (MLIs) in the cerebellum is mediated exclusively by glutamate spillover. Here, we show how CF stimulation functionally segregates MLIs based on their location relative to glutamate release. Excitation of MLIs that reside within the domain of spillover diffusion coordinates inhibition of MLIs outside the diffusion limit. CF excitation of MLIs is dependent on extrasynaptic NMDA receptors that enhance the spatial and temporal spread of CF signaling. Activity mediated by functionally segregated MLIs converges onto neighboring Purkinje cells (PCs) to generate a long-lasting biphasic change in inhibition. These data demonstrate how glutamate release from single CFs modulates excitability of neighboring PCs, thus expanding the influence of CFs on cerebellar cortical activity in a manner not predicted by anatomical connectivity. PMID:23707614

  11. FUNCTION FOLLOWS FORM: ACTIVATION OF SHAPE & FUNCTION FEATURES DURING OBJECT IDENTIFICATION

    PubMed Central

    Yee, Eiling; Huffstetler, Stacy; Thompson-Schill, Sharon L.

    2011-01-01

    Most theories of semantic memory characterize knowledge of a given object as comprising a set of semantic features. But how does conceptual activation of these features proceed during object identification? We present the results of a pair of experiments that demonstrate that object recognition is a dynamically unfolding process in which function follows form. We used eye movements to explore whether activating one object’s concept leads to the activation of others that share perceptual (shape) or abstract (function) features. Participants viewed four-picture displays and clicked on the picture corresponding to a heard word. In critical trials, the conceptual representation of one of the objects in the display was similar in shape or function (i.e., its purpose) to the heard word. Importantly, this similarity was not apparent in the visual depictions (e.g., for the target “frisbee,” the shape-related object was a triangular slice of pizza – a shape that a frisbee cannot take); preferential fixations on the related object were therefore attributable to overlap of the conceptual representations on the relevant features. We observed relatedness effects for both shape and function, but shape effects occurred earlier than function effects. We discuss the implications of these findings for current accounts of the representation of semantic memory. PMID:21417543

  12. [Functional activity of bone marrow-derived peptides (myelopeptides)].

    PubMed

    Mikhaĭlova, A A; Petrov, R V

    2009-12-01

    The review describes structure and functions of bone marrow-derived peptides (myelopeptides). The final biological effects of these endogenous bioregulators (antitumor, antiviral, anti-infectious, antileukemia etc.) are due to their immunocorrecting and differentiating activity. Myelopeptides are the integral parts of the immune homeostasis maintenance system. Nowadays, medical preparations with no side effects and natural mechanisms of action are being developed on the basis of synthesized myelopeptides.

  13. Comparative studies of brain activation with MEG and functional MRI

    SciTech Connect

    George, J.S.; Aine, C.J.; Sanders, J.A.; Lewine, J.D.; Caprihan, A.

    1993-12-31

    The past two years have witnessed the emergence of MRI as a functional imaging methodology. Initial demonstrations involved the injection of a paramagnetic contrast agent and required ultrafast echo planar imaging capability to adequately resolve the passage of the injected bolus. By measuring the local reduction in image intensity due to magnetic susceptibility, it was possible to calculate blood volume, which changes as a function of neural activation. Later developments have exploited endogenous contrast mechanisms to monitor changes in blood volume or in venous blood oxygen content. Recently, we and others have demonstrated that it is possible to make such measurements in a clinical imager, suggesting that the large installed base of such machines might be utilized for functional imaging. Although it is likely that functional MRI (fMRI) will subsume some of the clinical and basic neuroscience applications now touted for MEG, it is also clear that these techniques offer different largely complementary, capabilities. At the very least, it is useful to compare and cross-validate the activation maps produced by these techniques. Such studies will be valuable as a check on results of neuromagnetic distributed current reconstructions and will allow better characterization of the relationship between neurophysiological activation and associated hemodynamic changes. A more exciting prospect is the development of analyses that combine information from the two modalities to produce a better description of underlying neural activity than is possible with either technique in isolation. In this paper we describe some results from initial comparative studies and outline several techniques that can be used to treat MEG and fMRI data within a unified computational framework.

  14. Intermediate scattering function of an anisotropic active Brownian particle

    NASA Astrophysics Data System (ADS)

    Kurzthaler, Christina; Leitmann, Sebastian; Franosch, Thomas

    2016-10-01

    Various challenges are faced when animalcules such as bacteria, protozoa, algae, or sperms move autonomously in aqueous media at low Reynolds number. These active agents are subject to strong stochastic fluctuations, that compete with the directed motion. So far most studies consider the lowest order moments of the displacements only, while more general spatio-temporal information on the stochastic motion is provided in scattering experiments. Here we derive analytically exact expressions for the directly measurable intermediate scattering function for a mesoscopic model of a single, anisotropic active Brownian particle in three dimensions. The mean-square displacement and the non-Gaussian parameter of the stochastic process are obtained as derivatives of the intermediate scattering function. These display different temporal regimes dominated by effective diffusion and directed motion due to the interplay of translational and rotational diffusion which is rationalized within the theory. The most prominent feature of the intermediate scattering function is an oscillatory behavior at intermediate wavenumbers reflecting the persistent swimming motion, whereas at small length scales bare translational and at large length scales an enhanced effective diffusion emerges. We anticipate that our characterization of the motion of active agents will serve as a reference for more realistic models and experimental observations.

  15. Interactions between occlusion and human brain function activities.

    PubMed

    Ohkubo, C; Morokuma, M; Yoneyama, Y; Matsuda, R; Lee, J S

    2013-02-01

    There are few review articles in the area of human research that focus on the interactions between occlusion and brain function. This systematic review discusses the effect of occlusion on the health of the entire body with a focus on brain function. Available relevant articles in English from 1999 to 2011 were assessed in an online database and as hard copies in libraries. The selected 19 articles were classified into the following five categories: chewing and tongue movements, clenching and grinding, occlusal splints and occlusal interference, prosthetic rehabilitation, and pain and stimulation. The relationships between the brain activity observed in the motor and sensory cortices and movements of the oral and maxillofacial area, such as those produced by gum chewing, tapping and clenching, were investigated. It was found that the sensorimotor cortex was also affected by the placement of the occlusal interference devices, splints and implant prostheses. Brain activity may change depending on the strength of the movements in the oral and maxillofacial area. Therefore, mastication and other movements stimulate the activity in the cerebral cortex and may be helpful in preventing degradation of a brain function. However, these findings must be verified by evidence gathered from more subjects.

  16. PIC Activation through Functional Interplay between Mediator and TFIIH.

    PubMed

    Malik, Sohail; Molina, Henrik; Xue, Zhu

    2017-01-06

    The multiprotein Mediator coactivator complex functions in large part by controlling the formation and function of the promoter-bound preinitiation complex (PIC), which consists of RNA polymerase II and general transcription factors. However, precisely how Mediator impacts the PIC, especially post-recruitment, has remained unclear. Here, we have studied Mediator effects on basal transcription in an in vitro transcription system reconstituted from purified components. Our results reveal a close functional interplay between Mediator and TFIIH in the early stages of PIC development. We find that under conditions when TFIIH is not normally required for transcription, Mediator actually represses transcription. TFIIH, whose recruitment to the PIC is known to be facilitated by the Mediator, then acts to relieve Mediator-induced repression to generate an active form of the PIC. Gel mobility shift analyses of PICs and characterization of TFIIH preparations carrying mutant XPB translocase subunit further indicate that this relief of repression is achieved through expending energy via ATP hydrolysis, suggesting that it is coupled to TFIIH's established promoter melting activity. Our interpretation of these results is that Mediator functions as an assembly factor that facilitates PIC maturation through its various stages. Whereas the overall effect of the Mediator is to stimulate basal transcription, its initial engagement with the PIC generates a transcriptionally inert PIC intermediate, which necessitates energy expenditure to complete the process.

  17. [Histidine triad protein superfamily--biological function and enzymatic activity].

    PubMed

    Krakowiak, Agnieszka; Fryc, Izabela

    2012-01-01

    The HIT superfamily consists of proteins that share the histidine triad motif, His-X-His-X-His-X-X (where X is a hydrophobic amino acid), which constitutes enzymatic catalytic center. These enzymes act as nucleotidylyl hydrolase or transferase, and the mutation of the second histidine in the triad abolishes their activity. HIT proteins were found ubiquitous in all organisms and they were classified into 5 branches, which are represented by human proteins: HINT1, FHIT, Aprataxin, GALT and DCPS. Because HINT1 orthologs, which belong to the evolutionally oldest family branch, were found from prokaryotes to eukaryotes, it is clear that HIT motif was conserved during the evolution what means that the enzymatic activity is necessary for functions of these proteins. However, in few cases, e.g. HINT1 and FHIT, the connection between the biological function and the enzymatic activity is still obscure. In this review, the relations between biology and activity for 7 HIT proteins, which were found in human, are highlighted.

  18. Platelet Serotonin Transporter Function Predicts Default-Mode Network Activity

    PubMed Central

    Kasess, Christian H.; Meyer, Bernhard M.; Hofmaier, Tina; Diers, Kersten; Bartova, Lucie; Pail, Gerald; Huf, Wolfgang; Uzelac, Zeljko; Hartinger, Beate; Kalcher, Klaudius; Perkmann, Thomas; Haslacher, Helmuth; Meyer-Lindenberg, Andreas; Kasper, Siegfried; Freissmuth, Michael; Windischberger, Christian; Willeit, Matthäus; Lanzenberger, Rupert; Esterbauer, Harald; Brocke, Burkhard; Moser, Ewald; Sitte, Harald H.; Pezawas, Lukas

    2014-01-01

    Background The serotonin transporter (5-HTT) is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT) from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence. Methods A functional magnetic resonance study was performed in 48 healthy subjects and maximal 5-HT uptake velocity (Vmax) was assessed in blood platelets. We used a mixed-effects multilevel analysis technique (MEMA) to test for linear relationships between whole-brain, blood-oxygen-level dependent (BOLD) activity and platelet Vmax. Results The present study demonstrates that increases in platelet Vmax significantly predict default-mode network (DMN) suppression in healthy subjects independent of genetic variation within SLC6A4. Furthermore, functional connectivity analyses indicate that platelet Vmax is related to global DMN activation and not intrinsic DMN connectivity. Conclusion This study provides evidence that platelet Vmax predicts global DMN activation changes in healthy subjects. Given previous reports on platelet-synaptosomal Vmax coupling, results further suggest an important role of neuronal 5-HT reuptake in DMN regulation. PMID:24667541

  19. Everyday activity patterns and sensory functioning in old age.

    PubMed

    Marsiske, M; Klumb, P; Baltes, M M

    1997-09-01

    In the present study the authors investigated the relationship between visual and auditory acuity and everyday activity functioning. Participants were 516 older adults (70-103 years; equal numbers of men and women) who were members of the age-stratified Berlin Aging Study. Two categories of everyday activity functioning, perceived competence with basic activities of daily living (BaCo; basic competence) and amount of participation in discretionary social and leisure tasks (ExCo; expanded competence), were examined. The results revealed that sensory acuity, particularly vision, was a significant predictor of both BaCo and ExCo (rs ranging from .32 to .47). Indeed, hearing and vision could explain most of the age-related variance in everyday activities. At the same time, in the context of a broader model, evidence for the differential prediction of BaCo and ExCo was found, although there was also evidence for strong general age-related predictive variance that was common to both measures. Discussion focuses on the role of sensory acuity constructs as mediators of age-related variance in psychological and behavioral outcomes and the potential causal implications of this mediation.

  20. The impact of chromospheric activity on observed initial mass functions

    SciTech Connect

    Stassun, Keivan G.; Scholz, Aleks; Dupuy, Trent J.; Kratter, Kaitlin M.

    2014-12-01

    Using recently established empirical calibrations for the impact of chromospheric activity on the radii, effective temperatures, and estimated masses of active low-mass stars and brown dwarfs, we reassess the shape of the initial mass function (IMF) across the stellar/substellar boundary in the Upper Sco star-forming region (age ∼ 5-10 Myr). We adjust the observed effective temperatures to warmer values using the observed strength of the chromospheric Hα emission, and redetermine the estimated masses of objects using pre-main-sequence evolutionary tracks in the H-R diagram. The effect of the activity-adjusted temperatures is to shift the objects to higher masses by 3%-100%. While the slope of the resulting IMF at substellar masses is not strongly changed, the peak of the IMF does shift from ≈0.06 to ≈0.11 M {sub ☉}. Moreover, for objects with masses ≲ 0.2 M {sub ☉}, the ratio of brown dwarfs to stars changes from ∼80% to ∼33%. These results suggest that activity corrections are essential for studies of the substellar mass function, if the masses are estimated from spectral types or from effective temperatures.

  1. Immunomodulation by Blastomyces dermatitidis: functional activity of murine peritoneal macrophages.

    PubMed Central

    McDaniel, L S; Cozad, G C

    1983-01-01

    Cell-mediated immunity plays the dominant role in the immune response of mice to Blastomyces dermatitidis infections. Since macrophages play an important role in cell-mediated immunity, the interactions between sensitized murine peritoneal macrophages and the yeast phase of B. dermatitidis were investigated. Scanning electron microscopy showed that the sensitized macrophages readily phagocytized B. dermatitidis yeast cells. In addition, there appeared to be activation of metabolic pathways within the sensitized macrophages, as indicated by increased chemiluminescence activity during phagocytosis. Sensitized macrophages were significantly better at controlling intracellular proliferation of the yeast cells when compared to nonsensitized cells. This was determined by disruption of macrophages and plating for viable yeasts. Scanning electron microscope observations offered further substantiation. Experiments with Candida albicans indicated that B. dermatitidis non-specifically activated macrophages. At 2 h postphagocytosis, 30% fewer C. albicans in B. dermatitidis-activated macrophages were able to form germ tubes. These studies demonstrated the multiple potential of activated macrophages with regard to their functional activity. Images PMID:6840859

  2. Quantitative evaluation of activation state in functional brain imaging.

    PubMed

    Hu, Zhenghui; Ni, Pengyu; Liu, Cong; Zhao, Xiaohu; Liu, Huafeng; Shi, Pengcheng

    2012-10-01

    Neuronal activity can evoke the hemodynamic change that gives rise to the observed functional magnetic resonance imaging (fMRI) signal. These increases are also regulated by the resting blood volume fraction (V (0)) associated with regional vasculature. The activation locus detected by means of the change in the blood-oxygen-level-dependent (BOLD) signal intensity thereby may deviate from the actual active site due to varied vascular density in the cortex. Furthermore, conventional detection techniques evaluate the statistical significance of the hemodynamic observations. In this sense, the significance level relies not only upon the intensity of the BOLD signal change, but also upon the spatially inhomogeneous fMRI noise distribution that complicates the expression of the results. In this paper, we propose a quantitative strategy for the calibration of activation states to address these challenging problems. The quantitative assessment is based on the estimated neuronal efficacy parameter [Formula: see text] of the hemodynamic model in a voxel-by-voxel way. It is partly immune to the inhomogeneous fMRI noise by virtue of the strength of the optimization strategy. Moreover, it is easy to incorporate regional vascular information into the activation detection procedure. By combining MR angiography images, this approach can remove large vessel contamination in fMRI signals, and provide more accurate functional localization than classical statistical techniques for clinical applications. It is also helpful to investigate the nonlinear nature of the coupling between synaptic activity and the evoked BOLD response. The proposed method might be considered as a potentially useful complement to existing statistical approaches.

  3. [Biodiversity and Function Analyses of BIOLAK Activated Sludge Metagenome].

    PubMed

    Tian, Mei; Liu, Han-hu; Shen, Xin; Zhao, Fang-qing; Chen, Shuai; Yao, Yong-jia

    2015-05-01

    The BIOLAK is a multi-stage activated sludge process, which has been successfully promoted worldwide. However, the biological community and function of the BIOLAK activated sludge ( the core component in the process) have not been reported so far. In this study, taking Lianyungang Dapu Industrial Zone WWTP as an example, a large-scale metagenomic data (428 588 high-quality DNA sequences) of the BIOLAK activated sludge were obtained by means of a new generation of high-throughput sequencing technology. Amazing biodiversity was revealed in the BIOLAK activated sludge, which included 47 phyla, 872 genera and 1351 species. There were 33 phyla identified in the Bacteria domain (289 933 sequences). Proteohacteria was the most abundant phylum (62.54%), followed by Bacteroidetes (11.29%), Nitrospirae ( 5. 65%) and Planctomycetes (4.79%), suggesting that these groups played a key role in the BIOLAK wastewater treatment system. Among the 748 bacterial genera, Nitrospira (5.60%) was the most prevalent genus, which was a key group in the nitrogen cycle. Followed by Gemmatimonas (2.45%), which was an important genus in the biological phosphorus removal process. In Archaea domain (1019 sequences), three phyla and 39 genera were detected. In Eukaryota domain (1055 sequences), 60 genera and 10 phyla were identified, among which Ciliophora was the largest phylum (257 sequences). Meanwhile, 448 viral sequences were detected in the BIOLAK sludge metagenome, which were dominated by bacteriophages. The proportions of nitrogen, aromatic compounds and phosphorus metabolism in the BIOLAK sludge were 2.50%, 2.28% and 1.56%, respectively, which were higher than those in the sludge of United States and Australia. Among four processes of nitrogen metabolism, denitrification-related genes were most abundant (80.81%), followed by ammonification (12.78%), nitrification,(4.38%) and nitrogen fixation (2.04%). In conclusion, the BIOLAK activated sludge had amazing biodiversity, meanwhile

  4. Influence of gold nanoparticles on platelets functional activity in vitro

    NASA Astrophysics Data System (ADS)

    Akchurin, Garif G.; Akchurin, George G.; Ivanov, Alexey N.; Kirichuk, Vyacheslav F.; Terentyuk, George S.; Khlebtsov, Boris N.; Khlebtsov, Nikolay G.

    2008-02-01

    Now in the leading biomedical centers of the world approved new technology of laser photothermal destruction of cancer cells using plasmon gold nanoparticles. Investigations of influence of gold nanoparticles on white rat platelets aggregative activity in vitro have been made. Platelet aggregation was investigated in platelet rich plasma (PRP) with help of laser analyzer 230 LA <>, Russia). Aggregation inductor was ADP solution in terminal concentration 2.5 micromole (<>, Russia). Gold nanoshells soluted in salt solution were used for experiments. Samples of PRP were incubated with 50 or 100 μl gold nanoshells solution in 5 minute, after that we made definition ADP induced platelet aggregation. We found out increase platelet function activity after incubation with nanoparticles solution which shown in maximum ADP-induced aggregation degree increase. Increase platelet function activity during intravenous nanoshells injection can be cause of thrombosis on patients. That's why before clinical application of cancer cell destruction based on laser photothermal used with plasmon gold nanoparticles careful investigations of thrombosis process and detail analyze of physiological blood parameters are very necessary.

  5. Exploring Electro-active Functionality of Transparent Oxide Materials

    NASA Astrophysics Data System (ADS)

    Hosono, Hideo

    2013-09-01

    Ceramics, one of the earliest materials used by humans, have been used since the Stone Age and are also one of the core materials supporting modern society. In this article, I will review the features of transparent oxides, the main components of ceramics, and the progress of research on their electro-active functionalities from the viewpoint of material design. Specifically, the emergence of the functionality of the cement component 12CaO.7Al2O3, the application of transparent oxide semiconductors to thin-film transistors for flat panel displays, and the design of wide-gap p-type semiconductors are introduced along with the progress in their research. In addition, oxide semiconductors are comprehensively discussed on the basis of the band lineup.

  6. Sigma-1 receptors modulate functional activity of rat splenocytes.

    PubMed

    Liu, Y; Whitlock, B B; Pultz, J A; Wolfe, S A

    1995-06-01

    Neuroleptics, opiates, and cocaine are commonly prescribed for or abused by humans. Although primarily used for their actions at other receptors in brain, these compounds also act at sigma receptors. We have previously identified sigma-1 receptors on human peripheral blood leukocytes and rat spleen, and in the present study we demonstrate a correlation between the pharmacology of these receptors and the ability of drugs to suppress concanavalin A-induced splenocyte proliferation. These results support the hypothesis that sigma-1 receptors regulate functional activities of immune cells, and suggest that sigma agonists may cause changes in immune competence in vivo.

  7. Synthesis and psychotropic activity of functionally substituted diaziridines and bisdiaziridines

    SciTech Connect

    Kostyanovskii, R.G.; Shustov, G.V.; Nabiev, O.G.; Denisenko, S.N.; Sukhanova, S.A.; Lavretskaya, E.F.

    1987-04-01

    The authors examine the psychotropic activity of diaziridines which differ considerable in their structures and the C- and N-substituents. Diaziridines are monoamine oxidase inhibitors in the brain and, thus, are potential antidepressants. The acute toxicities and some pharmacological effects of diaziridines are shown. Mice were used in the experiments. The bisdiaziridines obtained differ in their /sup 1/H and /sup 13/C NMR spectra. The effect is presented of functionally substituted diaziridines on the effects of reserpine, 5-hydroxytryptophan, tryptamine, corazole, and apomorphine hypothermia.

  8. Polymeric active coatings with functionality in vascular applications.

    PubMed

    Aguilar, María Rosa; Rodríguez, Gema; Fernández, Mar; Gallardo, Alberto; San Román, Julio

    2002-12-01

    Copolymers containing functional groups with activity as antiaggregating agents for platelets, based on random chains of metacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)]benzoate, TH, and 2-acrylamido-2-metylpropanesulfonic acid, AMPS, with AMPS molar fractions ranging from 0.1 to 0.4, have been prepared. The spectroscopical characterization and the in vitro swelling behavior have been studied, as well as the surface free energy, showing the copolymers an appropriate surface properties from a haemocompatible point of view. Preliminary in vitro tests using human blood have shown a promising antiaggregating behavior.

  9. Active membrane having uniform physico-chemically functionalized ion channels

    DOEpatents

    Gerald, II, Rex E; Ruscic, Katarina J; Sears, Devin N; Smith, Luis J; Klingler, Robert J; Rathke, Jerome W

    2012-09-24

    The present invention relates to a physicochemically-active porous membrane for electrochemical cells that purports dual functions: an electronic insulator (separator) and a unidirectional ion-transporter (electrolyte). The electrochemical cell membrane is activated for the transport of ions by contiguous ion coordination sites on the interior two-dimensional surfaces of the trans-membrane unidirectional pores. One dimension of the pore surface has a macroscopic length (1 nm-1000 .mu.m) and is directed parallel to the direction of an electric field, which is produced between the cathode and the anode electrodes of an electrochemical cell. The membrane material is designed to have physicochemical interaction with ions. Control of the extent of the interactions between the ions and the interior pore walls of the membrane and other materials, chemicals, or structures contained within the pores provides adjustability of the ionic conductivity of the membrane.

  10. Biological activity of lactoferrin-functionalized biomimetic hydroxyapatite nanocrystals

    PubMed Central

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

    2014-01-01

    The emergence of bacterial strains resistant to antibiotics is a general public health problem. Progress in developing new molecules with antimicrobial properties has been made. In this study, we evaluated the biological activity of a hybrid nanocomposite composed of synthetic biomimetic hydroxyapatite surface-functionalized by lactoferrin (LF-HA). We evaluated the antimicrobial, anti-inflammatory, and antioxidant properties of LF-HA and found that the composite was active against both Gram-positive and Gram-negative bacteria, and that it modulated proinflammatory and anti-inflammatory responses and enhanced antioxidant properties as compared with LF alone. These results indicate the possibility of using LF-HA as an antimicrobial system and biomimetic hydroxyapatite as a candidate for innovative biomedical applications. PMID:24623976

  11. Mitogen-activated protein kinases in male reproductive function

    PubMed Central

    Li, Michelle W.M.; Mruk, Dolores D.; Cheng, C. Yan

    2009-01-01

    Recent studies have shown that male reproductive function is modulated via the mitogen-activated protein kinase (MAPK) cascade. The MAPK cascade is involved in numerous male reproductive processes, including spermatogenesis, sperm maturation and activation, capacitation and acrosome reaction, before fertilization of the oocyte. In this review, we discuss the latest findings in this rapidly developing field regarding the role of MAPK in male reproduction in animal models and in human spermatozoa in vitro. This research will facilitate the design of future studies in humans, although much work is needed before this information can be used to manage male infertility and environmental toxicant-induced testicular injury in men, such as blood–testis-barrier disruption. PMID:19303360

  12. Innate response activator B cells: origins and functions

    PubMed Central

    Swirski, Filip K.

    2015-01-01

    Innate response activator (IRA) B cells are a subset of B-1a derived B cells that produce the growth factors granulocyte macrophage colony stimulating factor and IL-3. In mouse models of sepsis and pneumonia, B-1a B cells residing in serosal sites recognize bacteria, migrate to the spleen or lung, and differentiate to IRA B cells that then contribute to the host response by amplifying inflammation and producing polyreactive IgM. In atherosclerosis, IRA B cells accumulate in the spleen, where they promote extramedullary hematopoiesis and activate classical dendritic cells. In this review, we focus on the ontogeny and function of IRA B cells in acute and chronic inflammation. PMID:25957266

  13. Inferring deep-brain activity from cortical activity using functional near-infrared spectroscopy.

    PubMed

    Liu, Ning; Cui, Xu; Bryant, Daniel M; Glover, Gary H; Reiss, Allan L

    2015-03-01

    Functional near-infrared spectroscopy (fNIRS) is an increasingly popular technology for studying brain function because it is non-invasive, non-irradiating and relatively inexpensive. Further, fNIRS potentially allows measurement of hemodynamic activity with high temporal resolution (milliseconds) and in naturalistic settings. However, in comparison with other imaging modalities, namely fMRI, fNIRS has a significant drawback: limited sensitivity to hemodynamic changes in deep-brain regions. To overcome this limitation, we developed a computational method to infer deep-brain activity using fNIRS measurements of cortical activity. Using simultaneous fNIRS and fMRI, we measured brain activity in 17 participants as they completed three cognitive tasks. A support vector regression (SVR) learning algorithm was used to predict activity in twelve deep-brain regions using information from surface fNIRS measurements. We compared these predictions against actual fMRI-measured activity using Pearson's correlation to quantify prediction performance. To provide a benchmark for comparison, we also used fMRI measurements of cortical activity to infer deep-brain activity. When using fMRI-measured activity from the entire cortex, we were able to predict deep-brain activity in the fusiform cortex with an average correlation coefficient of 0.80 and in all deep-brain regions with an average correlation coefficient of 0.67. The top 15% of predictions using fNIRS signal achieved an accuracy of 0.7. To our knowledge, this study is the first to investigate the feasibility of using cortical activity to infer deep-brain activity. This new method has the potential to extend fNIRS applications in cognitive and clinical neuroscience research.

  14. Endothelial RIG-I activation impairs endothelial function

    SciTech Connect

    Asdonk, Tobias; Nickenig, Georg; Zimmer, Sebastian

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer RIG-I activation impairs endothelial function in vivo. Black-Right-Pointing-Pointer RIG-I activation alters HCAEC biology in vitro. Black-Right-Pointing-Pointer EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 {mu}g of the RIG-ligand 3pRNA (RNA with triphosphate at the 5 Prime end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

  15. Bimanual passive movement: functional activation and inter-regional coupling.

    PubMed

    Macaluso, Emiliano; Cherubini, Andrea; Sabatini, Umberto

    2007-01-01

    The aim of this study was to investigate intra-regional activation and inter-regional connectivity during passive movement. During fMRI, a mechanic device was used to move the subject's index and middle fingers. We assessed four movement conditions (unimanual left/right, bimanual symmetric/asymmetric), plus Rest. A conventional intra-regional analysis identified the passive stimulation network, including motor cortex, primary and secondary somatosensory cortex, plus the cerebellum. The posterior (sensory) part of the sensory-motor activation around the central sulcus showed a significant modulation according to the symmetry of the bimanual movement, with greater activation for asymmetric compared to symmetric movements. A second set of fMRI analyses assessed condition-dependent changes of coupling between sensory-motor regions around the superior central sulcus and the rest of the brain. These analyses showed a high inter-regional covariation within the entire network activated by passive movement. However, the specific experimental conditions modulated these patterns of connectivity. Highest coupling was observed during the Rest condition, and the coupling between homologous sensory-motor regions around the left and right central sulcus was higher in bimanual than unimanual conditions. These findings demonstrate that passive movement can affect the connectivity within the sensory-motor network. We conclude that implicit detection of asymmetry during bimanual movement relies on associative somatosensory region in post-central areas, and that passive stimulation reduces the functional connectivity within the passive movement network. Our findings open the possibility to combine passive movement and inter-regional connectivity as a tool to investigate the functionality of the sensory-motor system in patients with very poor mobility.

  16. ESCRT-III on endosomes: new functions, new activation pathway.

    PubMed

    Woodman, Philip

    2016-01-15

    The multivesicular body (MVB) pathway sorts ubiquitinated membrane cargo to intraluminal vesicles (ILVs) within the endosome, en route to the lysosomal lumen. The pathway involves the sequential action of conserved protein complexes [endosomal sorting complexes required for transport (ESCRTs)], culminating in the activation by ESCRT-II of ESCRT-III, a membrane-sculpting complex. Although this linear pathway of ESCRT activation is widely accepted, a study by Luzio and colleagues in a recent issue of the Biochemical Journal suggests that there is greater complexity in ESCRT-III activation, at least for some MVB cargoes. They show that ubiquitin-dependent sorting of major histocompatibility complex (MHC) class I to the MVB requires the central ESCRT-III complex but does not involve either ESCRT-II or functional links between ESCRT-II and ESCRT-III. Instead, they propose that MHC class I utilizes histidine-domain protein tyrosine phosphatase (HD-PTP), a non-canonical ESCRT interactor, to promote ESCRT-III activation.

  17. Moonlighting transcriptional activation function of a fungal sulfur metabolism enzyme

    PubMed Central

    Levati, Elisabetta; Sartini, Sara; Bolchi, Angelo; Ottonello, Simone; Montanini, Barbara

    2016-01-01

    Moonlighting proteins, including metabolic enzymes acting as transcription factors (TF), are present in a variety of organisms but have not been described in higher fungi so far. In a previous genome-wide analysis of the TF repertoire of the plant-symbiotic fungus Tuber melanosporum, we identified various enzymes, including the sulfur-assimilation enzyme phosphoadenosine-phosphosulfate reductase (PAPS-red), as potential transcriptional activators. A functional analysis performed in the yeast Saccharomyces cerevisiae, now demonstrates that a specific variant of this enzyme, PAPS-red A, localizes to the nucleus and is capable of transcriptional activation. TF moonlighting, which is not present in the other enzyme variant (PAPS-red B) encoded by the T. melanosporum genome, relies on a transplantable C-terminal polypeptide containing an alternating hydrophobic/hydrophilic amino acid motif. A similar moonlighting activity was demonstrated for six additional proteins, suggesting that multitasking is a relatively frequent event. PAPS-red A is sulfur-state-responsive and highly expressed, especially in fruitbodies, and likely acts as a recruiter of transcription components involved in S-metabolism gene network activation. PAPS-red B, instead, is expressed at low levels and localizes to a highly methylated and silenced region of the genome, hinting at an evolutionary mechanism based on gene duplication, followed by epigenetic silencing of this non-moonlighting gene variant. PMID:27121330

  18. Activities and Programs That Improve Children’s Executive Functions

    PubMed Central

    Diamond, Adele

    2014-01-01

    Executive functions (EFs; e.g., reasoning, working memory, and self-control) can be improved. Good news indeed, since EFs are critical for school and job success and for mental and physical health. Various activities appear to improve children’s EFs. The best evidence exists for computer-based training, traditional martial arts, and two school curricula. Weaker evidence, though strong enough to pass peer review, exists for aerobics, yoga, mindfulness, and other school curricula. Here I address what can be learned from the research thus far, including that EFs need to be progressively challenged as children improve and that repeated practice is key. Children devote time and effort to activities they love; therefore, EF interventions might use children’s motivation to advantage. Focusing narrowly on EFs or aerobic activity alone appears not to be as efficacious in improving EFs as also addressing children’s emotional, social, and character development (as do martial arts, yoga, and curricula shown to improve EFs). Children with poorer EFs benefit more from training; hence, training might provide them an opportunity to “catch up” with their peers and not be left behind. Remaining questions include how long benefits of EF training last and who benefits most from which activities. PMID:25328287

  19. Running wheel activity restores MPTP-induced functional deficits.

    PubMed

    Fredriksson, Anders; Stigsdotter, Ingels Maria; Hurtig, Anders; Ewalds-Kvist, Béatrice; Archer, Trevor

    2011-03-01

    -Dopa tests. Running wheel activity attenuated markedly the loss of dopamine due to repeated administrations of MPTP. BDNF protein level in the parietal cortex was elevated by the MPTP insult and increased further by physical exercise. Physical running wheel exercise alleviated both the functional and biomarker expressions of MPTP-induced parkinsonism.

  20. Functional interaction of hepatic nuclear factor-4 and peroxisome proliferator-activated receptor-gamma coactivator 1alpha in CYP7A1 regulation is inhibited by a key lipogenic activator, sterol regulatory element-binding protein-1c.

    PubMed

    Ponugoti, Bhaskar; Fang, Sungsoon; Kemper, Jongsook Kim

    2007-11-01

    Insulin inhibits transcription of cholesterol 7alpha-hydroxylase (Cyp7a1), a key gene in bile acid synthesis, and the hepatic nuclear factor-4 (HNF-4) site in the promoter was identified as a negative insulin response sequence. Using a fasting/feeding protocol in mice and insulin treatment in HepG2 cells, we explored the inhibition mechanisms. Expression of sterol regulatory element-binding protein-1c (SREBP-1c), an insulin-induced lipogenic factor, inversely correlated with Cyp7a1 expression in mouse liver. Interaction of HNF-4 with its coactivator, peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), was observed in livers of fasted mice and was reduced after feeding. Conversely, HNF-4 interaction with SREBP-1c was increased after feeding. In vitro studies suggested that SREBP-1c competed with PGC-1alpha for direct interaction with the AF2 domain of HNF-4. Reporter assays showed that SREBP-1c, but not of a SREBP-1c mutant lacking the HNF-4 interacting domain, inhibited HNF-4/PGC-1alpha transactivation of Cyp7a1. SREBP-1c also inhibited PGC-1alpha-coactivation of estrogen receptor, constitutive androstane receptor, pregnane X receptor, and farnesoid X receptor, implying inhibition of HNF-4 by SREBP-1c could extend to other nuclear receptors. In chromatin immunoprecipitation studies, HNF-4 binding to the promoter was not altered, but PGC-1alpha was dissociated, SREBP-1c and histone deacetylase-2 (HDAC2) were recruited, and acetylation of histone H3 was decreased upon feeding. Adenovirus-mediated expression of a SREBP-1c dominant-negative mutant, which blocks the interaction of SREBP-1c and HNF-4, partially but significantly reversed the inhibition of Cyp7a1 after feeding. Our data show that SREBP-1c functions as a non-DNA-binding inhibitor and mediates, in part, suppression of Cyp7a1 by blocking functional interaction of HNF-4 and PGC-1alpha. This mechanism may be relevant to known repression of many other HNF-4 target genes upon

  1. Transition metal activation and functionalization of carbon-hydrogen bonds

    SciTech Connect

    Jones, W.D.

    1992-06-01

    We are investigating the fundamental thermodynamic and kinetic factors that influence carbon-hydrogen bond activation at homogeneous transition metal centers and the conversion of hydrocarbons into functionalized products of potential use to the chemical industry. Advances have been made in both understanding the interactions of hydrocarbons with metals and in the functionalization of hydrocarbons. We have found that RhCl(PR{sub 3}){sub 2}(CNR) complexes can catalyze the insertion of isonitriles into the C-H bonds or arenes upon photolysis. The mechanism of these reactions was found to proceed by way of initial phosphine dissociation, followed by C-H activation and isonitrile insertion. We have also examined reactions of a series of arenes with (C{sub 5}Me{sub 5})Rh(PMe{sub 3})PhH and begun to map out the kinetic and thermodynamic preferences for arene coordination. The effects of resonance, specifically the differences in the Hueckel energies of the bound vs free ligand, are now believed to fully control the C-H activation/{eta}{sup 2}-coordination equilibria. We have begun to examine the reactions of rhodium isonitrile pyrazolylborates for alkane and arene C-H bond activation. A new, labile, carbodiimide precursor has been developed for these studies. We have completed studies of the reactions of (C{sub 5}Me{sub 5})Rh(PMe{sub 3})H{sub 2} with D{sub 2} and PMe{sub 3} that indicate that both {eta}{sup 5} {yields} {eta}{sup 3} ring slippage and metal to ring hydride migration occur more facilely than thermal reductive elimination of H{sub 2}. We have examined the reactions of heterocycles with (C{sub 5}Me{sub 5})Rh(PMe{sub 3})PhH and found that pyrrole and furan undergo C-H or N-H activation. Thiophene, however, undergoes C-S bond oxidative addition, and the mechanism of activation has been shown to proceed through sulfur coordination prior to C-S insertion.

  2. 20 CFR 641.864 - What functions and activities constitute programmatic activity costs?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., DEPARTMENT OF LABOR PROVISIONS GOVERNING THE SENIOR COMMUNITY SERVICE EMPLOYMENT PROGRAM Administrative... training, as described in § 641.540, which may be provided before commencing or during a community service... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false What functions and activities...

  3. 20 CFR 641.864 - What functions and activities constitute programmatic activity costs?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., DEPARTMENT OF LABOR PROVISIONS GOVERNING THE SENIOR COMMUNITY SERVICE EMPLOYMENT PROGRAM Administrative... training, as described in § 641.540, which may be provided before commencing or during a community service... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false What functions and activities...

  4. Structural and functional maturation of active zones in large synapses.

    PubMed

    Cano, Raquel; Torres-Benito, Laura; Tejero, Rocío; Biea, Anca I; Ruiz, Rocío; Betz, William J; Tabares, Lucía

    2013-02-01

    Virtually all functions of the nervous system rely upon synapses, the sites of communication between neurons and between neurons and other cells. Synapses are complex structures, each one comprising hundreds of different types of molecules working in concert. They are organized by adhesive and scaffolding molecules that align presynaptic vesicular release sites, namely, active zones, with postsynaptic neurotransmitter receptors, thereby allowing rapid and reliable intercellular communication. Most synapses are relatively small, and acting alone exerts little effect on their postsynaptic partners. Some, however, are much larger and stronger, reliably driving the postsynaptic cell to its action potential threshold, acting essentially as electrical relays of excitation. These large synapses are among the best understood, and two of these are the subject of this review, namely, the vertebrate neuromuscular junction and the calyx of Held synapse in the mammalian auditory pathway of the brain stem. Both synapses undergo through a complex and well-coordinated maturation process, during which time the molecular elements and the biophysical properties of the secretory machinery are continuously adjusted to the synapse size and to the functional requirements. We here review the morphological and functional changes occurring during postnatal maturation, noting particular similarities and differences between these two large synapses.

  5. Active chemisorption sites in functionalized ionic liquids for carbon capture.

    PubMed

    Cui, Guokai; Wang, Jianji; Zhang, Suojiang

    2016-07-25

    Development of novel technologies for the efficient and reversible capture of CO2 is highly desired. In the last decade, CO2 capture using ionic liquids has attracted intensive attention from both academia and industry, and has been recognized as a very promising technology. Recently, a new approach has been developed for highly efficient capture of CO2 by site-containing ionic liquids through chemical interaction. This perspective review focuses on the recent advances in the chemical absorption of CO2 using site-containing ionic liquids, such as amino-based ionic liquids, azolate ionic liquids, phenolate ionic liquids, dual-functionalized ionic liquids, pyridine-containing ionic liquids and so on. Other site-containing liquid absorbents such as amine-based solutions, switchable solvents, and functionalized ionic liquid-amine blends are also investigated. Strategies have been discussed for how to activate the existent reactive sites and develop novel reactive sites by physical and chemical methods to enhance CO2 absorption capacity and reduce absorption enthalpy. The carbon capture mechanisms of these site-containing liquid absorbents are also presented. Particular attention has been paid to the latest progress in CO2 capture in multiple-site interactions by amino-free anion-functionalized ionic liquids. In the last section, future directions and prospects for carbon capture by site-containing ionic liquids are outlined.

  6. Preparation of functionalized and metal-impregnated activated carbon by a single-step activation method

    NASA Astrophysics Data System (ADS)

    Dastgheib, Seyed A.; Ren, Jianli; Rostam-Abadi, Massoud; Chang, Ramsay

    2014-01-01

    A rapid method to prepare functionalized and metal-impregnated activated carbon from coal is described in this paper. A mixture of ferric chloride and a sub-bituminous coal was used to demonstrate simultaneous coal activation, chlorine functionalization, and iron/iron oxides impregnation in the resulting porous carbon products. The FeCl3 concentration in the mixture, the method to prepare the FeCl3-coal mixture (solid mixing or liquid impregnation), and activation atmosphere and temperature impacted the surface area and porosity development, Cl functionalization, and iron species impregnation and dispersion in the carbon products. Samples activated in nitrogen or a simulated flue gas at 600 or 1000 °C for 1-2 min had surface areas up to ∼800 m2/g, bulk iron contents up to 18 wt%, and surface chlorine contents up to 27 wt%. Potential catalytic and adsorption application of the carbon materials was explored in catalytic wet air oxidation (CWAO) of phenol and adsorption of ionic mercury from aqueous solutions. Results indicated that impregnated activated carbons outperformed their non-impregnated counterparts in both the CWAO and adsorption tests.

  7. Functional neuroimaging of conversion disorder: The role of ancillary activation

    PubMed Central

    Burke, Matthew J.; Ghaffar, Omar; Staines, W. Richard; Downar, Jonathan; Feinstein, Anthony

    2014-01-01

    Background Previous functional neuroimaging studies investigating the neuroanatomy of conversion disorder have yielded inconsistent results that may be attributed to small sample sizes and disparate methodologies. The objective of this study was to better define the functional neuroanatomical correlates of conversion disorder. Methods Ten subjects meeting clinical criteria for unilateral sensory conversion disorder underwent fMRI during which a vibrotactile stimulus was applied to anesthetic and sensate areas. A block design was used with 4 s of stimulation followed by 26 s of rest, the pattern repeated 10 times. Event-related group averages of the BOLD response were compared between conditions. Results All subjects were right-handed females, with a mean age of 41. Group analyses revealed 10 areas that had significantly greater activation (p < .05) when stimulation was applied to the anesthetic body part compared to the contralateral sensate mirror region. They included right paralimbic cortices (anterior cingulate cortex and insula), right temporoparietal junction (angular gyrus and inferior parietal lobule), bilateral dorsolateral prefrontal cortex (middle frontal gyri), right orbital frontal cortex (superior frontal gyrus), right caudate, right ventral-anterior thalamus and left angular gyrus. There was a trend for activation of the somatosensory cortex contralateral to the anesthetic region to be decreased relative to the sensate side. Conclusions Sensory conversion symptoms are associated with a pattern of abnormal cerebral activation comprising neural networks implicated in emotional processing and sensory integration. Further study of the roles and potential interplay of these networks may provide a basis for an underlying psychobiological mechanism of conversion disorder. PMID:25379447

  8. Unique functional properties of a member of the Fushi Tarazu-Factor 1 family from Schistosoma mansoni

    PubMed Central

    Bertin, Benjamin; Sasorith, Souphatta; Caby, Stéphanie; Oger, Frédérik; Cornette, Jocelyne; Wurtz, Jean-Marie; Pierce, Raymond J.

    2004-01-01

    SmFtz-F1 (Schistosoma mansoni Fushi Tarazu-Factor 1) belongs to the Ftz-F1 subfamily of nuclear receptors, but displays marked structural differences compared with its mammalian homologues SF-1 (steroidogenic factor-1) or liver receptor homologue-1. These include a long F domain (104 amino acids), an unusually large hinge region (133 amino acids) and a poorly conserved E-domain. Here, using Gal4 constructs and a mammalian two-hybrid assay, we have characterized the roles of these specific regions both in the transcriptional activity of the receptor and in its interactions with cofactors. Our results have shown that, although the AF-2 (activation function-2) region is the major activation function of the receptor, both the F and D domains are essential for AF-2-dependent activity. Modelling of SmFtz-F1 LBD (ligand-binding domain) and structure-guided mutagenesis allowed us to show the important role of helix H1 in maintaining the structural conformation of the LBD, and suggested that its autonomous transactivation activity, also observed with SF-1, is fortuitous. This strategy also allowed us to study an eventual ligand-dependence for this orphan receptor, the predicted three-dimensional models suggesting that the SmFtz-F1 LBD contains a large and well-defined ligand-binding pocket sealed by two arginine residues orientated towards the interior of the cavity. Mutation of these two residues provoked a loss of transcriptional activity of the receptor, and strongly reduced its interaction with SRC1 (steroid receptor cofactor-1), suggesting a ligand-dependent activity for SmFtz-F1. Taken together, our results argue for original and specific functional activities for this platyhelminth nuclear receptor. PMID:15104535

  9. Sensorimotor Peripheral Nerve Function and Physical Activity in Older Men

    PubMed Central

    Lange-Maia, Brittney S.; Cauley, Jane A.; Newman, Anne B.; Boudreau, Robert M.; Jakicic, John M.; Glynn, Nancy W.; Zivkovic, Sasa; Dam, Tien; Caserotti, Paolo; Cawthon, Peggy M.; Orwoll, Eric S.; Strotmeyer, Elsa S.

    2017-01-01

    We determined whether sensorimotor peripheral nerve (PN) function was associated with physical activity (PA) in older men. The Osteoporotic Fractures in Men Study Pittsburgh, PA, site (n=328, age 78.8±4.7 years), conducted PN testing, including: peroneal motor and sural sensory nerve conduction (latencies, amplitudes: CMAP and SNAP for motor and sensory amplitude, respectively), 1.4g/10g monofilament (dorsum of the great toe), and neuropathy symptoms. ANOVA and multivariate linear regression modeled PN associations with PA (Physical Activity Scale for the Elderly (PASE) and SenseWear Armband). After multivariable adjustment, better motor latency was associated with higher PASE scores (160.5±4.8 vs 135.6±6.7, p<0.01). Those without vs. with neuropathy symptoms had higher PASE scores (157.6±5.3 vs 132.9±7.1, p<0.01). Better vs. worse SNAP was associated with slightly more daily vigorous activity (9.5±0.8 vs. 7.3±0.7, p=0.05). Other PN measures were not associated with PA. Certain PN measures were associated with lower PA, suggesting a potential pathway for disability. PMID:26964668

  10. Kallikreins - the melting pot of activity and function

    PubMed Central

    Kalinska, Magdalena; Meyer-Hoffert, Ulf; Kantyka, Tomasz; Potempa, Jan

    2015-01-01

    The human tissue kallikrein and kallikrein-related peptidases (KLKs), encoded by the largest contiguous cluster of protease genes in the human genome, are secreted serine proteases with diverse expression patterns and physiological roles. Because of the broad spectrum of processes that are modulated by kallikreins, these proteases are the subject of extensive investigations. This review brings together basic information about the biochemical properties affecting enzymatic activity, with highlights on post-translational modifications, especially glycosylation. Additionally, we present the current state of knowledge regarding the physiological functions of KLKs in major human organs and outline recent discoveries pertinent to the involvement of kallikreins in cell signaling and in viral infections. Despite the current depth of knowledge of these enzymes, many questions regarding the roles of kallikreins in health and disease remain unanswered. PMID:26408415

  11. Metabolically active functional food ingredients for weight control.

    PubMed

    Kovacs, E M R; Mela, D J

    2006-02-01

    The scale of the obesity epidemic creates a pressing consumer need as well as an enormous business opportunity for successful development and marketing of food products with added benefits for weight control. A number of proposed functional food ingredients have been shown to act post-absorptively to influence substrate utilization or thermogenesis. Characteristics and supporting data on conjugated linoleic acid, diglycerides, medium-chain triglycerides, green tea, ephedrine, caffeine, capsaicin and calcium, are reviewed here, giving examples of how these could act to alter energy expenditure or appetite control. Consideration is also given to other factors, in addition to efficacy, which must be satisfied to get such ingredients into foods. We conclude that, for each of the safe, putatively metabolically active agents, there remain gaps in clinical evidence or knowledge of mechanisms, which need to be addressed in order to specify the dietary conditions and food product compositions where these ingredients could be of most benefit for weight control.

  12. Platelet function and fibrinolytic activity following distance running.

    PubMed

    Knudsen, J B; Brodthagen, U; Gormsen, J; Jordal, R; Nørregaard-Hansen, K; Paulev, P E

    1982-11-01

    6 long distance runners from the Danish marathon elite and 6 non-runners completed test runs of 28 and 12 km, respectively. Distance runners and non-runners showed the same responses in platelet function. We found a significant decrease in ADP induced platelet aggregability, a decreased serotonin release induced by ADP and collagen and an increase in platelet factor 4 immediately following the run. The antithrombin III levels remained constant. Euglobulin lysis time was shortened (by approximately 50%) and the plasminogen levels significantly increased. The last 2 findings indicate an equal increase in fibrinolytic activity during distance running in both groups. While short term, strenuous exercise induces platelet hyperaggregation, long term distance running induces a state of exhaustion of platelet aggregation capacity.

  13. Regulation of glomerulotubular balance: flow-activated proximal tubule function.

    PubMed

    Wang, Tong; Weinbaum, Sheldon; Weinstein, Alan M

    2017-03-07

    The purpose of this review is to summarize our knowledge and understanding of the physiological importance and the mechanisms underlying flow-activated proximal tubule transport. Since the earliest micropuncture studies of mammalian proximal tubule, it has been recognized that tubular flow is an important regulator of sodium, potassium, and acid-base transport in the kidney. Increased fluid flow stimulates Na(+) and HCO3(-) absorption in the proximal tubule via stimulation of Na/H-exchanger isoform 3 (NHE3) and H(+)-ATPase. In the proximal tubule, brush border microvilli are the major flow sensors, which experience changes in hydrodynamic drag and bending moment as luminal flow velocity changes and which transmit the force of altered flow to cytoskeletal structures within the cell. The signal to NHE3 depends upon the integrity of the actin cytoskeleton; the signal to the H(+)-ATPase depends upon microtubules. We have demonstrated that alterations in fluid drag impact tubule function by modulating ion transporter availability within the brush border membrane of the proximal tubule. Beyond that, there is evidence that transporter activity within the peritubular membrane is also modulated by luminal flow. Secondary messengers that regulate the flow-mediated tubule function have also been delineated. Dopamine blunts the responsiveness of proximal tubule transporters to changes in luminal flow velocity, while a DA1 antagonist increases flow sensitivity of solute reabsorption. IP3 receptor-mediated intracellular Ca(2+) signaling is critical to transduction of microvillus drag. In this review, we summarize our findings of the regulatory mechanism of flow-mediated Na(+) and HCO3(-) transport in the proximal tubule and review available information about flow sensing and regulatory mechanism of glomerulotubular balance.

  14. Metaproteomics Provides Functional Insight into Activated Sludge Wastewater Treatment

    PubMed Central

    Wilmes, Paul; Wexler, Margaret; Bond, Philip L.

    2008-01-01

    Background Through identification of highly expressed proteins from a mixed culture activated sludge system this study provides functional evidence of microbial transformations important for enhanced biological phosphorus removal (EBPR). Methodology/Principal Findings A laboratory-scale sequencing batch reactor was successfully operated for different levels of EBPR, removing around 25, 40 and 55 mg/l P. The microbial communities were dominated by the uncultured polyphosphate-accumulating organism “Candidatus Accumulibacter phosphatis”. When EBPR failed, the sludge was dominated by tetrad-forming α-Proteobacteria. Representative and reproducible 2D gel protein separations were obtained for all sludge samples. 638 protein spots were matched across gels generated from the phosphate removing sludges. 111 of these were excised and 46 proteins were identified using recently available sludge metagenomic sequences. Many of these closely match proteins from “Candidatus Accumulibacter phosphatis” and could be directly linked to the EBPR process. They included enzymes involved in energy generation, polyhydroxyalkanoate synthesis, glycolysis, gluconeogenesis, glycogen synthesis, glyoxylate/TCA cycle, fatty acid β oxidation, fatty acid synthesis and phosphate transport. Several proteins involved in cellular stress response were detected. Conclusions/Significance Importantly, this study provides direct evidence linking the metabolic activities of “Accumulibacter” to the chemical transformations observed in EBPR. Finally, the results are discussed in relation to current EBPR metabolic models. PMID:18392150

  15. Functional Anatomy of T Cell Activation and Synapse Formation

    PubMed Central

    Fooksman, David R.; Vardhana, Santosh; Vasiliver-Shamis, Gaia; Liese, Jan; Blair, David; Waite, Janelle; Sacristán, Catarina; Victora, Gabriel; Zanin-Zhorov, Alexandra; Dustin, Michael L.

    2010-01-01

    T cell activation and function require a structured engagement of antigen-presenting cells. These cell contacts are characterized by two distinct dynamics in vivo: transient contacts resulting from promigratory junctions called immunological kinapses or prolonged contacts from stable junctions called immunological synapses. Kinapses operate in the steady state to allow referencing to self-peptide-MHC (pMHC) and searching for pathogen-derived pMHC. Synapses are induced by T cell receptor (TCR) interactions with agonist pMHC under specific conditions and correlate with robust immune responses that generate effector and memory T cells. High-resolution imaging has revealed that the synapse is highly coordinated, integrating cell adhesion, TCR recognition of pMHC complexes, and an array of activating and inhibitory ligands to promote or prevent T cell signaling. In this review, we examine the molecular components, geometry, and timing underlying kinapses and synapses. We integrate recent molecular and physiological data to provide a synthesis and suggest ways forward. PMID:19968559

  16. Suppressive Activity of Quercetin on Periostin Functions In Vitro.

    PubMed

    Irie, Shinji; Kashiwabara, Misako; Yamada, Asako; Asano, Kazuhito

    2016-01-01

    Periostin, a 90-kDa extracellular matrix protein, has been attracting attention as a novel biomarker of airway inflammatory diseases such as allergic rhinitis (AR) and asthma. Although oral administration of quercetin to patients with AR can favorably modify the clinical condition of this disease, the influence of quercetin on periostin functions is not well understood. The present study was, therefore, undertaken to examine the influence of quercetin on the production of both periostin and periostin-induced eosinophil chemoattractants from human nasal epithelial cells (HNEpC) in vitro. HNEpC were stimulated with 15.0 ng/ml interleukin (IL)-4 in the absence or presence of quercetin for 72 h. Periostin levels in the culture supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Addition of 4.0 μM quercetin into cell cultures suppressed periostin production from HNEpC that was induced by IL-4 stimulation through inhibitation of signal transducer and activator of transcription 6 (STAT6) activation. We then examined whether quercetin could inhibit production of the periostin-induced eosinophil chemoattractants, regulated on activation, normal T-cell expressed and secreted (RANTES) and eotaxin, from HNEpC. HNEpC were stimulated with 2.0 ng/ml periostin in the absence or presence of quercetin for 72 h. RANTES and eotaxin levels in culture supernatants were examined using ELISA. Treatment of HNEpC with quercetin at a concentration of 4.0 μM suppressed the ability of cells to produce RANTES and eotaxin. This suppression was mediated through suppression of activation of the transcription factor nuclear factor-kappa B (NF-κB) p65, as measured using ELISA, and of chemokine mRNA expression, as measured using reverse transcriptase-polymerase chain reaction (RT-PCR). These results strongly suggest that quercetin suppresses the production of both periostin and periostin-induced eosinophil chemoattractants from HNEpC and results in improvement of the

  17. Shoulder muscle activity and function in common shoulder rehabilitation exercises.

    PubMed

    Escamilla, Rafael F; Yamashiro, Kyle; Paulos, Lonnie; Andrews, James R

    2009-01-01

    , posterior tilt and ER. The serratus anterior also helps stabilize the medial border and inferior angle of the scapular, preventing scapular IR (winging) and anterior tilt. If normal scapular movements are disrupted by abnormal scapular muscle firing patterns, weakness, fatigue, or injury, the shoulder complex functions less efficiency and injury risk increases. Scapula position and humeral rotation can affect injury risk during humeral elevation. Compared with scapular protraction, scapular retraction has been shown to both increase subacromial space width and enhance supraspinatus force production during humeral elevation. Moreover, scapular IR and scapular anterior tilt, both of which decrease subacromial space width and increase impingement risk, are greater when performing scaption with IR ('empty can') compared with scaption with ER ('full can'). There are several exercises in the literature that exhibit high to very high activity from the rotator cuff, deltoids and scapular muscles, such as prone horizontal abduction at 100 degrees abduction with ER, flexion and abduction with ER, 'full can' and 'empty can', D1 and D2 diagonal pattern flexion and extension, ER and IR at 0 degrees and 90 degrees abduction, standing extension from 90-0 degrees , a variety of weight-bearing upper extremity exercises, such as the push-up, standing scapular dynamic hug, forward scapular punch, and rowing type exercises. Supraspinatus activity is similar between 'empty can' and 'full can' exercises, although the 'full can' results in less risk of subacromial impingement. Infraspinatus and subscapularis activity have generally been reported to be higher in the 'full can' compared with the 'empty can', while posterior deltoid activity has been reported to be higher in the 'empty can' than the 'full can'.

  18. RNase H Activity: Structure, Specificity, and Function in Reverse Transcription

    PubMed Central

    Schultz, Sharon J.; Champoux, James J.

    2008-01-01

    This review compares the well-studied RNase H activities of human immunodeficiency virus, type 1 (HIV-1) and Moloney murine leukemia virus (MoMLV) reverse transcriptases. The RNase H domains of HIV-1 and MoMLV are structurally very similar, with functions assigned to conserved subregions like the RNase H primer grip and the connection subdomain, as well as to distinct features like the C-helix and loop in MoMLV RNase H. Like cellular RNases H, catalysis by the retroviral enzymes appears to involve a two-metal ion mechanism. Unlike cellular RNases H, the retroviral RNases H display three different modes of cleavage: internal, DNA 3′ end-directed, and RNA 5′ end-directed. All three modes of cleavage appear to have roles in reverse transcription. Nucleotide sequence is an important determinant of cleavage specificity with both enzymes exhibiting a preference for specific nucleotides at discrete positions flanking an internal cleavage site as well as during tRNA primer removal and plus-strand primer generation. RNA 5′ end-directed and DNA 3′ end-directed cleavages show similar sequence preferences at the positions closest to a cleavage site. A model for how RNase H selects cleavage sites is presented that incorporates both sequence preferences and the concept of a defined window for allowable cleavage from a recessed end. Finally, the RNase H activity of HIV-1 is considered as a target for anti-virals as well as a participant in drug resistance. PMID:18261820

  19. Chloride transport in functionally active phagosomes isolated from Human neutrophils

    PubMed Central

    Aiken, Martha L.; Painter, Richard G.; Zhou, Yun; Wang, Guoshun

    2012-01-01

    Chloride anion is critical for hypochlorous acid (HOCl) production and microbial killing in neutrophil phagosomes. However, the molecular mechanism by which this anion is transported to the organelle is poorly understood. In this report, membrane-enclosed and functionally active phagosomes were isolated from human neutrophils by using opsonized paramagnetic latex microspheres and a rapid magnetic separation method. The phagosomes recovered were highly enriched for specific protein markers associated with this organelle such as lysosomal-associated membrane protein-1, myeloperoxidase (MPO), lactoferrin, and NADPH oxidase. When FITC–dextran was included in the phagocytosis medium, the majority of the isolated phagosomes retained the fluorescent label after isolation, indicative of intact membrane structure. Flow cytometric measurement of acridine orange, a fluorescent pH indicator, in the purified phagosomes demonstrated that the organelle in its isolated state was capable of transporting protons to the phagosomal lumen via the vacuolar-type ATPase proton pump (V-ATPase). When NADPH was supplied, the isolated phagosomes constitutively oxidized dihydrorhodamine 123, indicating their ability to produce hydrogen peroxide. The preparations also showed a robust production of HOCl within the phagosomal lumen when assayed with the HOCl-specific fluorescent probe R19-S by flow cytometry. MPO-mediated iodination of the proteins covalently conjugated to the phagocytosed beads was quantitatively measured. Phagosomal uptake of iodide and protein iodination were significantly blocked by chloride channel inhibitors, including CFTRinh-172 and NPPB. Further experiments determined that the V-ATPase-driving proton flux into the isolated phagosomes required chloride cotransport, and the cAMP-activated CFTR chloride channel was a major contributor to the chloride transport. Taken together, the data suggest that the phagosomal preparation described herein retains ion transport

  20. Manipulation of Rubisco: the amount, activity, function and regulation.

    PubMed

    Parry, M A J; Andralojc, P J; Mitchell, R A C; Madgwick, P J; Keys, A J

    2003-05-01

    Genetic modification to increase the specificity of Rubisco for CO(2) relative to O(2) and to increase the catalytic rate of Rubisco in crop plants would have great agronomic importance. The availability of three-dimensional structures of Rubisco at atomic resolution and the characterization of site-directed mutants have greatly enhanced the understanding of the catalytic mechanism of Rubisco. Considerable progress has been made in identifying natural variation in the catalytic properties of Rubisco from different species and in developing the tools for introducing both novel and foreign Rubisco genes into plants. The additional complexities of assembling copies of the two distinct polypeptide subunits of Rubisco into a functional holoenzyme in vivo (requiring sufficient expression, post-translational modification, interaction with chaperonins, and interaction with Rubisco activase) remain a major challenge. The consequences of changing the amount of Rubisco present in leaves have been investigated by the use of antisense constructs. The manipulation of genes encoding Rubisco activase has provided a means to investigate the regulation of Rubisco activity.

  1. Genetically enhancing mitochondrial antioxidant activity improves muscle function in aging.

    PubMed

    Umanskaya, Alisa; Santulli, Gaetano; Xie, Wenjun; Andersson, Daniel C; Reiken, Steven R; Marks, Andrew R

    2014-10-21

    Age-related skeletal muscle dysfunction is a leading cause of morbidity that affects up to half the population aged 80 or greater. Here we tested the effects of increased mitochondrial antioxidant activity on age-dependent skeletal muscle dysfunction using transgenic mice with targeted overexpression of the human catalase gene to mitochondria (MCat mice). Aged MCat mice exhibited improved voluntary exercise, increased skeletal muscle specific force and tetanic Ca(2+) transients, decreased intracellular Ca(2+) leak and increased sarcoplasmic reticulum (SR) Ca(2+) load compared with age-matched wild type (WT) littermates. Furthermore, ryanodine receptor 1 (the sarcoplasmic reticulum Ca(2+) release channel required for skeletal muscle contraction; RyR1) from aged MCat mice was less oxidized, depleted of the channel stabilizing subunit, calstabin1, and displayed increased single channel open probability (Po). Overall, these data indicate a direct role for mitochondrial free radicals in promoting the pathological intracellular Ca(2+) leak that underlies age-dependent loss of skeletal muscle function. This study harbors implications for the development of novel therapeutic strategies, including mitochondria-targeted antioxidants for treatment of mitochondrial myopathies and other healthspan-limiting disorders.

  2. Real-time segmentation by Active Geometric Functions.

    PubMed

    Duan, Qi; Angelini, Elsa D; Laine, Andrew F

    2010-06-01

    Recent advances in 4D imaging and real-time imaging provide image data with clinically important cardiac dynamic information at high spatial or temporal resolution. However, the enormous amount of information contained in these data has also raised a challenge for traditional image analysis algorithms in terms of efficiency. In this paper, a novel deformable model framework, Active Geometric Functions (AGF), is introduced to tackle the real-time segmentation problem. As an implicit framework paralleling to level-set, AGF has mathematical advantages in efficiency and computational complexity as well as several flexible feature similar to level-set framework. AGF is demonstrated in two cardiac applications: endocardial segmentation in 4D ultrasound and myocardial segmentation in MRI with super high temporal resolution. In both applications, AGF can perform real-time segmentation in several milliseconds per frame, which was less than the acquisition time per frame. Segmentation results are compared to manual tracing with comparable performance with inter-observer variability. The ability of such real-time segmentation will not only facilitate the diagnoses and workflow, but also enables novel applications such as interventional guidance and interactive image acquisition with online segmentation.

  3. Functional Activation of the Flagellar Type III Secretion Export Apparatus

    PubMed Central

    Phillips, Andrew M.; Calvo, Rebecca A.; Kearns, Daniel B.

    2015-01-01

    Flagella are assembled sequentially from the inside-out with morphogenetic checkpoints that enforce the temporal order of subunit addition. Here we show that flagellar basal bodies fail to proceed to hook assembly at high frequency in the absence of the monotopic protein SwrB of Bacillus subtilis. Genetic suppressor analysis indicates that SwrB activates the flagellar type III secretion export apparatus by the membrane protein FliP. Furthermore, mutants defective in the flagellar C-ring phenocopy the absence of SwrB for reduced hook frequency and C-ring defects may be bypassed either by SwrB overexpression or by a gain-of-function allele in the polymerization domain of FliG. We conclude that SwrB enhances the probability that the flagellar basal body adopts a conformation proficient for secretion to ensure that rod and hook subunits are not secreted in the absence of a suitable platform on which to polymerize. PMID:26244495

  4. Absolute exponential stability of recurrent neural networks with generalized activation function.

    PubMed

    Xu, Jun; Cao, Yong-Yan; Sun, Youxian; Tang, Jinshan

    2008-06-01

    In this paper, the recurrent neural networks (RNNs) with a generalized activation function class is proposed. In this proposed model, every component of the neuron's activation function belongs to a convex hull which is bounded by two odd symmetric piecewise linear functions that are convex or concave over the real space. All of the convex hulls are composed of generalized activation function classes. The novel activation function class is not only with a more flexible and more specific description of the activation functions than other function classes but it also generalizes some traditional activation function classes. The absolute exponential stability (AEST) of the RNN with a generalized activation function class is studied through three steps. The first step is to demonstrate the global exponential stability (GES) of the equilibrium point of original RNN with a generalized activation function being equivalent to that of RNN under all vertex functions of convex hull. The second step transforms the RNN under every vertex activation function into neural networks under an array of saturated linear activation functions. Because the GES of the equilibrium point of three systems are equivalent, the next stability analysis focuses on the GES of the equilibrium point of RNN system under an array of saturated linear activation functions. The last step is to study both the existence of equilibrium point and the GES of the RNN under saturated linear activation functions using the theory of M-matrix. In the end, a two-neuron RNN with a generalized activation function is constructed to show the effectiveness of our results.

  5. Canid progesterone receptors lack activation function 3 domain-dependent activity.

    PubMed

    Gracanin, Ana; van Wolferen, Monique E; Sartorius, Carol A; Brenkman, Arjan B; Schoonen, Willem G; Mol, Jan A

    2012-12-01

    Progesterone regulates multiple behavioral, physiological, and pathological aspects of female reproductive biology through its two progesterone receptors (PRs), PR-B and the truncated PR-A. PR-B is necessary for mammary gland development in mice and, compared with PR-A, is overall a stronger transactivator of target genes due to an additional activation function 3 (AF3) domain. In dogs, known for their high sensitivity to progesterone-induced mammary cancer, the PR-B function was studied. Canine PR (cPR)-B appeared to contain multiple mutations within AF3 core sequence motifs and lacks N-terminal ligand-independent posttranslational modifications. Consequently, cPR-B has a weak transactivation potential on progesterone-responsive mouse mammary tumor virus-luc and progesterone response element 2-luc reporters transiently transfected in hamster, human, or canine cells and also on known target genes FKBP5 and SGK in doxycycline-inducible, stable transfected cPR-B in canine mammary cells. The cPR-B function was restored to the level of human PR-B by the replacement of canine AF3 domain with the human one. The lack of AF3 domain-dependent transcriptional activity was unique for canids (gray wolf, red fox, and raccoon dog) and not present in closely related caniform species (brown bear, gray seal, and domestic ferret). Despite the limited transactivation potential, canids develop normal mammary glands and frequently mammary tumors. Therefore, these results question the role of PR-B in breast cancer development and may explain unique features of canid reproduction.

  6. Nutrition and function, with emphasis on physical activity.

    PubMed

    Torun, B; Viteri, F E

    1993-01-01

    Consumption of insufficient quantities of food would result to energy deficiency in children, and this can be prevented by early assessment of changes in physical activity. This paper focuses on the effects of general undernutrition on physical activity and on growth, behavior, and cognitive development in Mexico, Uganda, Colombia, and Guatemala. The paper contains studies investigating the influence of undernutrition on physical activity; total energy expenditure; level of physical fitness; influence of physical activity and growth; and relationship of physical activity with behavior and cognitive development. The level of energy expenditure between nutritional groups could be accounted for the smaller size of the body among undernourished children. On the other hand, physiological potential to physically perform work can be maintained by children with mild or moderate malnutrition, but their smaller size limits their output. Lastly, increased physical activity of children receiving food supplementation was associated with exploratory and behavioral differences compared with nonsupplemented children.

  7. The Effect of Heparin on Fibrinolytic Activity and Platelet Function

    DTIC Science & Technology

    2007-11-02

    following cardiopulmonary bypass is that heparin activates the fibrinolytic system , which may, in turn, adversely affect hemostasis. To understand better...the effects of heparin administration on the fibrinolytic system in vivo, we simulated the anticoagulant regimen of cardiopulmonary bypass...following heparinization, and demonstrated that heparin induces activation of the fibrinolytic system . We showed that the fibrinolytic system was

  8. Quantification of neural functional connectivity during an active avoidance task.

    PubMed

    Silva, Catia S; Hazrati, Mehrnaz K; Keil, Andreas; Principe, Jose C; Silva, Catia S; Hazrati, Mehrnaz K; Keil, Andreas; Principe, Jose C; Keil, Andreas; Principe, Jose C; Hazrati, Mehrnaz K; Silva, Catia S

    2016-08-01

    Many behavioral and cognitive processes are associated with spatiotemporal dynamic communication between brain areas. Thus, the quantification of functional connectivity with high temporal resolution is highly desirable for capturing in vivo brain function. However, brain functional network quantification from EEG recordings has been commonly used in a qualitative manner. In this paper, we consider pairwise dependence measures as random variables and estimate the pdf for each electrode of the arrangement. A metric imposed by the quadratic Cauchy-Schwartz Mutual Information quantifies these pdfs. We present the results by brain regions simplifying the analysis and visualization drastically. The proposed metric of functional connectivity quantification is addressed for temporal dependencies of the brain network that can be related to the task.

  9. Physical Activity as a Function of Women's Health.

    PubMed

    Đukanović, Nina; Mašić, Zoran; Kostovski, Žarko; Širić, Vesna; Blažević, Stipe

    2015-07-01

    Physical activity means any form of body movement that is associated with certain metabolic demands. At the same time, physical activity is one of the most important steps in the maintenance, protection and improvement of health. There is strong evidence to suggest that higher levels of physical activity are associated with numerous preventive effects and therapeutic effects in the treatment of many diseases. Although they account for a larger portion of the population, physical inactivity is more often registered in women, which can be attributed to a variety of reasons--ranging from anatomical and physiological to the socio-psychological. The present paper discusses some of the most important benefits associated with physical activity in women, to encourage their greater participation in various forms of physical activity.

  10. Building an Understanding of Functions: A Series of Activities for Pre-Calculus

    ERIC Educational Resources Information Center

    Carducci, Olivia M.

    2008-01-01

    Building block toys can be used to illustrate various concepts connected with functions including graphs and rates of change of linear and exponential functions, piecewise functions, and composition of functions. Five brief activities suitable for a pre-calculus course are described.

  11. Relationship between physical functioning and physical activity in the lifestyle interventions and independence for elders pilot

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVES: To determine whether participation in usual moderate-intensity or more-vigorous physical activity (MVPA) is associated with physical function performance and to identify sociodemographic, psychosocial, and disease-related covariates that may also compromise physical function performance....

  12. Functional modulation of AMP-activated protein kinase by cereblon.

    PubMed

    Lee, Kwang Min; Jo, Sooyeon; Kim, Hyunyoung; Lee, Jongwon; Park, Chul-Seung

    2011-03-01

    Mutations in cereblon (CRBN), a substrate binding component of the E3 ubiquitin ligase complex, cause a form of mental retardation in humans. However, the cellular proteins that interact with CRBN remain largely unknown. Here, we report that CRBN directly interacts with the α1 subunit of AMP-activated protein kinase (AMPK α1) and inhibits the activation of AMPK activation. The ectopic expression of CRBN reduces phosphorylation of AMPK α1 and, thus, inhibits the enzyme in a nutrient-independent manner. Moreover, AMPK α1 can be potently activated by suppressing endogenous CRBN using CRBN-specific small hairpin RNAs. Thus, CRBN may act as a negative modulator of the AMPK signaling pathway in vivo.

  13. Methodology for the systems engineering process. Volume 1: System functional activities

    NASA Technical Reports Server (NTRS)

    Nelson, J. H.

    1972-01-01

    Systems engineering is examined in terms of functional activities that are performed in the conduct of a system definition/design, and system development is described in a parametric analysis that combines functions, performance, and design variables. Emphasis is placed on identification of activities performed by design organizations, design specialty groups, as well as a central systems engineering organizational element. Identification of specific roles and responsibilities for doing functions, and monitoring and controlling activities within the system development operation are also emphasized.

  14. A bidirectional relationship between physical activity and executive function in older adults.

    PubMed

    Daly, Michael; McMinn, David; Allan, Julia L

    2014-01-01

    Physically active lifestyles contribute to better executive function. However, it is unclear whether high levels of executive function lead people to be more active. This study uses a large sample and multi-wave data to identify whether a reciprocal association exists between physical activity and executive function. Participants were 4555 older adults tracked across four waves of the English Longitudinal Study of Aging. In each wave executive function was assessed using a verbal fluency test and a letter cancelation task and participants reported their physical activity levels. Fixed effects regressions showed that changes in executive function corresponded with changes in physical activity. In longitudinal multilevel models low levels of physical activity led to subsequent declines in executive function. Importantly, poor executive function predicted reductions in physical activity over time. This association was found to be over 50% larger in magnitude than the contribution of physical activity to changes in executive function. This is the first study to identify evidence for a robust bidirectional link between executive function and physical activity in a large sample of older adults tracked over time.

  15. Antifouling activity of enzyme‐functionalized silica nanobeads

    PubMed Central

    Zanoni, Michele; Habimana, Olivier; Amadio, Jessica

    2015-01-01

    ABSTRACT The amelioration of biofouling in industrial processing equipment is critical for performance and reliability. While conventional biocides are effective in biofouling control, they are potentially hazardous to the environment and in some cases corrosive to materials. Enzymatic approaches have been shown to be effective and can overcome the disadvantages of traditional biocides, however they are typically uneconomic for routine biofouling control. The aim of this study was to design a robust and reusable enzyme‐functionalized nano‐bead system having biofilm dispersion properties. This work describes the biochemical covalent functionalization of silica‐based nanobeads (hereafter referred to as Si‐NanoB) with Proteinase K (PK). Results showed that PK‐functionalized Si‐NanoB are effective in dispersing both protein‐based model biofilms and structurally altering Pseudomonas fluorescens biofilms, with significant decreases in surface coverage and thickness of 30.1% and 38.85%, respectively, while increasing surface roughness by 19 % following 24 h treatments on bacterial biofilms. This study shows that enzyme‐functionalized nanobeads may potentially be an environmentally friendly and cost effective alternative to pure enzyme and chemical treatments. Biotechnol. Bioeng. 2016;113: 501–512. © 2015 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. PMID:26370186

  16. Actively Learning Specific Function Properties with Applications to Statistical Inference

    DTIC Science & Technology

    2007-12-01

    which are distant from their nearest neigh- bors . However, when searching for level-sets, we are less interested in the function away from the level...34 excludes openly gay , lesbian and bisexual students from receiving ROTC scholarships or serving in the military. Nevertheless, all ROTC classes at

  17. Antibiotic production by soil bacteria: diversity, activity and natural functions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The living components of soils, the micro- and macrobiota, play an essential role in several life support functions as they enable soils to recycle nutrients, inactive contaminants, suppress plant pathogens and serve as a suitable substrate for plant growth. Beneficial bacteria occur naturally in s...

  18. Light activated liposomes: Functionality and prospects in ocular drug delivery.

    PubMed

    Lajunen, Tatu; Nurmi, Riikka; Kontturi, Leena; Viitala, Lauri; Yliperttula, Marjo; Murtomäki, Lasse; Urtti, Arto

    2016-12-28

    Ocular drug delivery, especially to the retina and choroid, is a major challenge in drug development. Liposome technology may be useful in ophthalmology in enabling new routes of delivery, prolongation of drug action and intracellular drug delivery, but drug release from the liposomes should be controlled. For that purpose, light activation may be an approach to release drug at specified time and site in the eye. Technical advances have been made in the field of light activated drug release, particularly indocyanine green loaded liposomes are a promising approach with safe materials and effective light triggered release of small and large molecules. This review discusses the liposomal drug delivery with light activated systems in the context of ophthalmic drug delivery challenges.

  19. Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions.

    PubMed

    Pereira, Priscilla Aparecida Tartari; Bitencourt, Claudia da Silva; dos Santos, Daiane Fernanda; Nicolete, Roberto; Gelfuso, Guilherme Martins; Faccioli, Lúcia Helena

    2015-10-12

    Biodegradable lactic-co-glycolic acid (PLGA) microspheres (MS) improve the stability of biomolecules stability and allow enable their sustained release. Lipid mediators represent a strategy for improving host defense; however, most of these mediators, such as prostaglandin D2 (PGD2), have low water solubility and are unstable. The present study aimed to develop and characterize MS loaded with PGD2 (PGD2-MS) to obtain an innovative tool to activate macrophages. PGD2-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process, and the size, zeta potential, surface morphology and encapsulation efficiency were determined. It was also evaluated in vitro the phagocytic index, NF-κB activation, as well as nitric oxide and cytokine production by alveolar macrophages (AMs) in response to PGD2-MS. PGD2-MS were spherical with a diameter of 5.0±3.3 μm and regular surface, zeta potential of -13.4±5.6 mV, and 36% of encapsulation efficiency, with 16-26% release of entrapped PGD2 at 4 and 48 h, respectively. PGD2-MS were more efficiently internalized by AMs than unloaded-MS, and activated NF-κB more than free PGD2. Moreover, PGD2-MS stimulated the production of nitric oxide, TNF-α, IL-1β, and TGF-β, more than free PGD2, indicating that microencapsulation increased the activating effect of PGD2 on cells. In LPS-pre-treated AMs, PGD2-MS decreased the release of IL-6 but increased the production of nitric oxide and IL-1β. These results show that the morphological characteristics of PGD2-MS facilitated interaction with, and activation of phagocytic cells; moreover, PGD2-MS retained the biological activities of PGD2 to trigger effector mechanisms in AMs. It is suggested that PGD2-MS represent a strategy for therapeutic intervention in the lungs of immunocompromised subjects.

  20. Patterns of functional enzyme activity in fungus farming ambrosia beetles

    PubMed Central

    2012-01-01

    Introduction In wood-dwelling fungus-farming weevils, the so-called ambrosia beetles (Curculionidae: Scolytinae and Platypodinae), wood in the excavated tunnels is used as a medium for cultivating fungi by the combined action of digging larvae (which create more space for the fungi to grow) and of adults sowing and pruning the fungus. The beetles are obligately dependent on the fungus that provides essential vitamins, amino acids and sterols. However, to what extent microbial enzymes support fungus farming in ambrosia beetles is unknown. Here we measure (i) 13 plant cell-wall degrading enzymes in the fungus garden microbial consortium of the ambrosia beetle Xyleborinus saxesenii, including its primary fungal symbionts, in three compartments of laboratory maintained nests, at different time points after gallery foundation and (ii) four specific enzymes that may be either insect or microbially derived in X. saxesenii adult and larval individuals. Results We discovered that the activity of cellulases in ambrosia fungus gardens is relatively small compared to the activities of other cellulolytic enzymes. Enzyme activity in all compartments of the garden was mainly directed towards hemicellulose carbohydrates such as xylan, glucomannan and callose. Hemicellulolytic enzyme activity within the brood chamber increased with gallery age, whereas irrespective of the age of the gallery, the highest overall enzyme activity were detected in the gallery dump material expelled by the beetles. Interestingly endo-β-1,3(4)-glucanase activity capable of callose degradation was identified in whole-body extracts of both larvae and adult X. saxesenii, whereas endo-β-1,4-xylanase activity was exclusively detected in larvae. Conclusion Similar to closely related fungi associated with bark beetles in phloem, the microbial symbionts of ambrosia beetles hardly degrade cellulose. Instead, their enzyme activity is directed mainly towards comparatively more easily accessible hemicellulose

  1. Spatial Correlation Function of the Chandra Selected Active Galactic Nuclei

    NASA Technical Reports Server (NTRS)

    Yang, Y.; Mushotzky, R. F.; Barger, A. J.; Cowie, L. L.

    2006-01-01

    We present the spatial correlation function analysis of non-stellar X-ray point sources in the Chandra Large Area Synoptic X-ray Survey of Lockman Hole Northwest (CLASXS). Our 9 ACIS-I fields cover a contiguous solid angle of 0.4 deg(exp 2) and reach a depth of 3 x 10(exp -15) erg/square cm/s in the 2-8 keV band. We supplement our analysis with data from the Chandra Deep Field North (CDFN). The addition of this field allows better probe of the correlation function at small scales. A total of 233 and 252 sources with spectroscopic information are used in the study of the CLASXS and CDFN fields respectively. We calculate both redshift-space and projected correlation functions in co-moving coordinates, averaged over the redshift range of 0.1 < z < 3.0, for both CLASXS and CDFN fields for a standard cosmology with Omega(sub Lambda) = 0.73,Omega(sub M) = 0.27, and h = 0.71 (H(sub 0) = 100h km/s Mpc(exp -1). The correlation function for the CLASXS field over scales of 3 Mpc< s < 200 Mpc can be modeled as a power-law of the form xi(s) = (S/SO)(exp - gamma), with gamma = 1.6(sup +0.4 sub -0.3) and S(sub o) = 8.0(sup +.14 sub -1.5) Mpc. The redshift-space correlation function for CDFN on scales of 1 Mpc< s < 100 Mpc is found to have a similar correlation length so = 8.55(sup +0.74 sub -0.74) Mpc, but a shallower slope (gamma = 1.3 +/- 0.1). The real-space correlation functions derived from the projected correlation functions, are found to be tau(sub 0 = 8.1(sup +1.2 sub -2.2) Mpc, and gamma = 2.1 +/- 0.5 for the CLASXS field, and tau(sub 0) = 5.8(sup +.1.0 sub -1.5) Mpc, gamma = 1.38(sup +0.12 sub -0.14 for the CDFN field. By comparing the real- and redshift-space correlation functions in the combined CLASXS and CDFN samples, we are able to estimate the redshift distortion parameter Beta = 0.4 +/- 0.2 at an effective redshift z = 0.94. We compare the correlation functions for hard and soft spectra sources in the CLASXS field and find no significant difference between the

  2. Management with willow short rotation coppice increase the functional gene diversity and functional activity of a heavy metal polluted soil.

    PubMed

    Xue, K; van Nostrand, J D; Vangronsveld, J; Witters, N; Janssen, J O; Kumpiene, J; Siebielec, G; Galazka, R; Giagnoni, L; Arenella, M; Zhou, J-Z; Renella, G

    2015-11-01

    We studied the microbial functional diversity, biochemical activity, heavy metals (HM) availability and soil toxicity of Cd, Pb and Zn contaminated soils, kept under grassland or short rotation coppice (SRC) to attenuate the risks associated with HM contamination and restore the soil ecological functions. Soil microbial functional diversity was analyzed by the GeoChip, a functional gene microarray containing probes for genes involved in nutrient cycling, metal resistance and stress response. Soil under SRC showed a higher abundance of microbial genes involved in C, N, P and S cycles and resistance to various HM, higher microbial biomass, respiration and enzyme activity rates, and lower HM availability than the grassland soil. The linkages between functional genes of soil microbial communities and soil chemical properties, HM availability and biochemical activity were also investigated. Soil toxicity and N, P and Pb availability were important factors in shaping the microbial functional diversity, as determined by CCA. We concluded that in HM contaminated soils the microbial functional diversity was positively influenced by SRC management through the reduction of HM availability and soil toxicity increase of nutrient cycling. The presented results can be important in predicting the long term environmental sustainability of plant-based soil remediation.

  3. Temporal dynamics of activation of thematic and functional knowledge during conceptual processing of manipulable artifacts.

    PubMed

    Kalénine, Solène; Mirman, Daniel; Middleton, Erica L; Buxbaum, Laurel J

    2012-09-01

    The current research aimed at specifying the activation time course of different types of semantic information during object conceptual processing and the effect of context on this time course. We distinguished between thematic and functional knowledge and the specificity of functional similarity. Two experiments were conducted with healthy older adults using eye tracking in a word-to-picture matching task. The time course of gaze fixations was used to assess activation of distractor objects during the identification of manipulable artifact targets (e.g., broom). Distractors were (a) thematically related (e.g., dustpan), (b) related by a specific function (e.g., vacuum cleaner), or (c) related by a general function (e.g., sponge). Growth curve analyses were used to assess competition effects when target words were presented in isolation (Experiment 1) and embedded in contextual sentences of different generality levels (Experiment 2). In the absence of context, there was earlier and shorter lasting activation of thematically related as compared to functionally related objects. The time course difference was more pronounced for general functions than specific functions. When contexts were provided, functional similarities that were congruent with context generality level increased in salience with earlier activation of those objects. Context had little impact on thematic activation time course. These data demonstrate that processing a single manipulable artifact concept implicitly activates thematic and functional knowledge with different time courses and that context speeds activation of context-congruent functional similarity.

  4. Self-Assembling Protein Nanostructures - Towards Active Functionality

    DTIC Science & Technology

    2011-04-22

    to this scaffold. These active nanoscaffolds were also embedded in permeable films and grown from surfaces. In the case of organophosphorous ...quaternary structure, amyloid fibril, organophosphorous hydrolase, enzyme Juliet Gerrard University of Canterbury 20 Kirkwood Ave Ilam 8041 - REPORT... organophosphorous hydrolase, a significant increase in thermal stability was observed. Two papers were published in Biotechnology Progress and a new

  5. Functionally charged nanosize particles differentially activate BV2 microglia.

    EPA Science Inventory

    The effect of particle surface charge on the biological activation of immortalized mouse microglia (BV2) was examined. Nanosize (860-950 nm) spherical polystyrene microparticles (SPM) were coated with carboxyl (COOH-) or dimethyl amino (CH3)2-N- groups to give a net negative or p...

  6. Twist1 activity thresholds define multiple functions in limb development.

    PubMed

    Krawchuk, Dayana; Weiner, Shoshana J; Chen, You-Tzung; Lu, Benson C; Costantini, Frank; Behringer, Richard R; Laufer, Ed

    2010-11-01

    The basic helix-loop-helix transcription factor Twist1 is essential for normal limb development. Twist1(-/-) embryos die at midgestation. However, studies on early limb buds found that Twist1(-/-) mutant limb mesenchyme has an impaired response to FGF signaling from the apical ectodermal ridge, which disrupts the feedback loop between the mesenchyme and AER, and reduces and shifts anteriorly Shh expression in the zone of polarizing activity. We have combined Twist1 null, hypomorph and conditional alleles to generate a Twist1 allelic series that survives to birth. As Twist1 activity is reduced, limb skeletal defects progress from preaxial polydactyly to girdle reduction combined with hypoplasia, aplasia or mirror symmetry of all limb segments. With reduced Twist1 activity there is striking and progressive upregulation of ectopic Shh expression in the anterior of the limb, combined with an anterior shift in the posterior Shh domain, which is expressed at normal intensity, and loss of the posterior AER. Consequently limb outgrowth is initially impaired, before an ectopic anterior Shh domain expands the AER, promoting additional growth and repatterning. Reducing the dosage of FGF targets of the Etv gene family, which are known repressors of Shh expression in anterior limb mesenchyme, strongly enhances the anterior skeletal phenotype. Conversely this and other phenotypes are suppressed by reducing the dosage of the Twist1 antagonist Hand2. Our data support a model whereby multiple Twist1 activity thresholds contribute to early limb bud patterning, and suggest how particular combinations of skeletal defects result from differing amounts of Twist1 activity.

  7. Twist1 activity thresholds define multiple functions in limb development

    PubMed Central

    Krawchuk, Dayana; Weiner, Shoshana J.; Chen, You-Tzung; Lu, Benson; Costantini, Frank; Behringer, Richard R.; Laufer, Ed

    2010-01-01

    Summary The basic helix-loop-helix transcription factor Twist1 is essential for normal limb development. Twist1−/− embryos die at midgestation. However, studies on early limb buds found that Twist1−/− mutant limb mesenchyme has an impaired response to FGF signaling from the apical ectodermal ridge, which disrupts the feedback loop between the mesenchyme and AER, and reduces and shifts anteriorly Shh expression in the zone of polarizing activity. We have combined Twist1 null, hypomorph and conditional alleles to generate a Twist1 allelic series that survives to birth. As Twist1 activity is reduced, limb skeletal defects progress from preaxial polydactyly to girdle reduction combined with hypoplasia, aplasia or mirror symmetry of all limb segments. With reduced Twist1 activity there is striking and progressive upregulation of ectopic Shh expression in the anterior of the limb, combined with an anterior shift in the posterior Shh domain, which is expressed at normal intensity, and loss of the posterior AER. Consequently limb outgrowth is initially impaired, before an ectopic anterior Shh domain expands the AER, promoting additional growth and repatterning. Reducing the dosage of FGF targets of the Etv gene family, which are known repressors of Shh expression in the anterior limb mesenchyme, strongly enhances the anterior skeletal phenotype. Conversely this and other phenotypes are suppressed by reducing the dosage of the Twist1 antagonist Hand2. Our data support a model whereby multiple Twist1 activity thresholds contribute to early limb bud patterning, and suggest how particular combinations of skeletal defects result from differing amounts of Twist1 activity. PMID:20732316

  8. Guide RNA functional modules direct Cas9 activity and orthogonality.

    PubMed

    Briner, Alexandra E; Donohoue, Paul D; Gomaa, Ahmed A; Selle, Kurt; Slorach, Euan M; Nye, Christopher H; Haurwitz, Rachel E; Beisel, Chase L; May, Andrew P; Barrangou, Rodolphe

    2014-10-23

    The RNA-guided Cas9 endonuclease specifically targets and cleaves DNA in a sequence-dependent manner and has been widely used for programmable genome editing. Cas9 activity is dependent on interactions with guide RNAs, and evolutionarily divergent Cas9 nucleases have been shown to work orthogonally. However, the molecular basis of selective Cas9:guide-RNA interactions is poorly understood. Here, we identify and characterize six conserved modules within native crRNA:tracrRNA duplexes and single guide RNAs (sgRNAs) that direct Cas9 endonuclease activity. We show the bulge and nexus are necessary for DNA cleavage and demonstrate that the nexus and hairpins are instrumental in defining orthogonality between systems. In contrast, the crRNA:tracrRNA complementary region can be modified or partially removed. Collectively, our results establish guide RNA features that drive DNA targeting by Cas9 and open new design and engineering avenues for CRISPR technologies.

  9. Functional Nanoparticles Activate a Decellularized Liver Scaffold for Blood Detoxification.

    PubMed

    Xu, Fen; Kang, Tianyi; Deng, Jie; Liu, Junli; Chen, Xiaolei; Wang, Yuan; Ouyang, Liang; Du, Ting; Tang, Hong; Xu, Xiaoping; Chen, Shaochen; Du, Yanan; Shi, Yujun; Qian, Zhiyong; Wei, Yuquan; Deng, Hongxin; Gou, Maling

    2016-04-01

    Extracorporeal devices have great promise for cleansing the body of virulence factors that are caused by venomous injuries, bacterial infections, and biological weaponry. The clinically used extracorporeal devices, such as artificial liver-support systems that are mainly based on dialysis or electrostatic interaction, are limited to remove a target toxin. Here, a liver-mimetic device is shown that consists of decellularized liver scaffold (DLS) populated with polydiacetylene (PDA) nanoparticles. DLS has the gross shape and 3D architecture of a liver, and the PDA nanoparticles selectively capture and neutralize the pore-forming toxins (PFTs). This device can efficiently and target-orientedly remove PFTs in human blood ex vivo without changing blood components or activating complement factors, showing potential application in antidotal therapy. This work provides a proof-of-principle for blood detoxification by a nanoparticle-activated DLS, and can lead to the development of future medical devices for antidotal therapy.

  10. Musculoskeletal Function and Obesity: Implications for Physical Activity.

    PubMed

    Shultz, Sarah P; Byrne, Nuala M; Hills, Andrew P

    2014-09-01

    However quantified, obesity is a global health problem of significant magnitude. The condition is no longer limited to the developed world, with an increasing proportion of low-to-middle income countries burdened by obesity and its comorbidities. Specifically, obesity is a risk factor for a raft of psychosocial, physiological, cardiovascular, and metabolic problems. The carriage of excess body weight, including an unhealthy proportion of body fat, also has important implications for musculoskeletal health. To date, this important relationship has not received as much attention by the research community. Coincidentally, there has been a heightened interest in the role of physical activity and exercise across the lifespan in the prevention, treatment and management of obesity. This paper considers some of the more common musculoskeletal problems in children, adolescents and adults with implications for the overweight and obese and their meaningful engagement in physical activity.

  11. Functional switching of GABAergic synapses by ryanodine receptor activation

    NASA Astrophysics Data System (ADS)

    Sun, Miao-Kun; Nelson, Thomas J.; Alkon, Daniel L.

    2000-10-01

    The role of the ryanodine receptor (RyR) in modifiability of synapses made by the basket interneurons onto the hippocampal CA1 pyramidal cells was examined in rats. Associating single-cell RyR activation with postsynaptic depolarization increased intracellular free Ca2+ concentrations and reversed the basket interneuron-CA1 inhibitory postsynaptic potential into an excitatory postsynaptic potential. This synaptic transformation was accompanied by a shift of the reversal potential from that of chloride toward that of bicarbonate. This inhibitory postsynaptic potential-excitatory postsynaptic potential transformation was prevented by blocking RyR or carbonic anhydrase. Associated postsynaptic depolarization and RyR activation, therefore, changes GABAergic synapses from excitation filters to amplifier and, thereby, shapes information flow through the hippocampal network.

  12. Nanoscale friction as a function of activation energies

    NASA Astrophysics Data System (ADS)

    Chong, W. W. F.; Rahnejat, H.

    2015-12-01

    Understanding the scale-dependence of friction is increasingly viewed as a critical quest. With progressively thinner films, mixed and boundary regimes of lubrication have become commonplace. Therefore, at the micro-scale a greater need for mitigating friction is desired in order to improve operational efficiency of many machines and mechanisms. Furthermore, there is a growing tendency to use low friction hard wear-resistant advanced coatings to guard against wear. In parallel, there has been much attention paid to lubricant rheology and formulation. However, only in recent times there has been an emerging view of lubricant-surface combination as a system. In this perspective it is essential to relate the observed and measured friction at component level to the underlying interactions in micro/nano-scales. This is the approach in this paper. Observed phenomenon at micro-scale are related back to the activation energies of lubricant-surface system, providing in particular results for surface modified Ni-SiC coated specimen in combination with formulated lubricants, the combination of which represent the lubricant-surface system of choice in cylinders of high performance race engine. The nano-scale conjunction of an AFM tip with lubricated surface-engineered specimen, subjected to various conjunctional loading and sliding kinematics is investigated. It is shown that the measured frictional characteristics can be adequately described in terms of activation energies in line with the Eyring’s thermal activation model for cases of fairly smooth asperity tip contact conjunctions.

  13. SysML model of exoplanet archive functionality and activities

    NASA Astrophysics Data System (ADS)

    Ramirez, Solange

    2016-08-01

    The NASA Exoplanet Archive is an online service that serves data and information on exoplanets and their host stars to help astronomical research related to search for and characterization of extra-solar planetary systems. In order to provide the most up to date data sets to the users, the exoplanet archive performs weekly updates that include additions into the database and updates to the services as needed. These weekly updates are complex due to interfaces within the archive. I will be presenting a SysML model that helps us perform these update activities in a weekly basis.

  14. Functionally diverse biotin-dependent enzymes with oxaloacetate decarboxylase activity.

    PubMed

    Lietzan, Adam D; St Maurice, Martin

    2014-02-15

    Biotin-dependent enzymes catalyze carboxylation, decarboxylation and transcarboxylation reactions that participate in the primary metabolism of a wide range of organisms. In all cases, the overall reaction proceeds via two half reactions that take place in physically distinct active sites. In the first half-reaction, a carboxyl group is transferred to the 1-N' of a covalently tethered biotin cofactor. The tethered carboxybiotin intermediate subsequently translocates to a second active site where the carboxyl group is either transferred to an acceptor substrate or, in some bacteria and archaea, is decarboxylated to biotin and CO2 in order to power the export of sodium ions from the cytoplasm. A homologous carboxyltransferase domain is found in three enzymes that catalyze diverse overall reactions: carbon fixation by pyruvate carboxylase, decarboxylation and sodium transport by the biotin-dependent oxaloacetate decarboxylase complex, and transcarboxylation by transcarboxylase from Propionibacterium shermanii. Over the past several years, structural data have emerged which have greatly advanced the mechanistic description of these enzymes. This review assembles a uniform description of the carboxyltransferase domain structure and catalytic mechanism from recent studies of pyruvate carboxylase, oxaloacetate decarboxylase and transcarboxylase, three enzymes that utilize an analogous carboxyltransferase domain to catalyze the biotin-dependent decarboxylation of oxaloacetate.

  15. Function of redox-active tyrosine in photosystem II.

    PubMed

    Ishikita, Hiroshi; Knapp, Ernst-Walter

    2006-06-01

    Water oxidation at photosystem II Mn-cluster is mediated by the redox-active tyrosine Y(Z). We calculated the redox potential (E(m)) of Y(Z) and its symmetrical counterpart Y(D), by solving the linearized Poisson-Boltzmann equation. The calculated E(m)(Y( )/Y(-)) were +926 mV/+694 mV for Y(Z)/Y(D) with the Mn-cluster in S2 state. Together with the asymmetric position of the Mn-cluster relative to Y(Z/D), differences in H-bond network between Y(Z) (Y(Z)/D1-His(190)/D1-Asn(298)) and Y(D) (Y(D)/D2-His(189)/D2-Arg(294)/CP47-Glu(364)) are crucial for E(m)(Y(Z/D)). When D1-His(190) is protonated, corresponding to a thermally activated state, the calculated E(m)(Y(Z)) was +1216 mV, which is as high as the E(m) for P(D1/D2). We observed deprotonation at CP43-Arg(357) upon S-state transition, which may suggest its involvement in the proton exit pathway. E(m)(Y(D)) was affected by formation of P(D2)(+) (but not P(D1)(+)) and sensitive to the protonation state of D2-Arg(180). This points to an electrostatic link between Y(D) and P(D2).

  16. Executive Functions in Learning Processes: Do They Benefit from Physical Activity?

    ERIC Educational Resources Information Center

    Barenberg, Jonathan; Berse, Timo; Dutke, Stephan

    2011-01-01

    As executive functions play an essential role in learning processes, approaches capable of enhancing executive functioning are of particular interest to educational psychology. Recently, the hypothesis has been advanced that executive functioning may benefit from changes in neurobiological processes induced by physical activity. The present…

  17. Altered Activity and Functional Connectivity of Superior Temporal Gyri in Anxiety Disorders: A Functional Magnetic Resonance Imaging Study

    PubMed Central

    Zhao, Xiaohu; Xi, Qian; Li, Chunbo; He, Hongjian

    2014-01-01

    Objective The prior functional MRI studies have demonstrated significantly abnormal activity in the bilateral superior temporal gyrus (STG) of anxiety patients. The purpose of the current investigation was to determine whether the abnormal activity in these regions was related to a loss of functional connectivity between these regions. Materials and Methods Ten healthy controls and 10 anxiety patients underwent noninvasive fMRI while actively listening to emotionally neutral words alternated by silence (Task 1) or threat-related words (Task 2). The participants were instructed to silently make a judgment of each word's valence (i.e., unpleasant, pleasant, or neutral). A coherence analysis was applied to the functional MRI data to examine the functional connectivity between the left and the right STG, which was selected as the primary region of interest on the basis of our prior results. Results The data demonstrated that the anxiety patients exhibited significantly increased activation in the bilateral STG than the normal controls. The functional connectivity analysis indicated that the patient group showed significantly decreased degree of connectivity between the bilateral STG during processing Task 2 compared to Task 1 (t = 2.588, p = 0.029). In addition, a significantly decreased connectivity was also observed in the patient group compared to the control group during processing Task 2 (t = 2.810, p = 0.012). Conclusion Anxiety patients may exhibit increased activity of the STG but decreased functional connectivity between the left and right STG, which may reflect the underlying neural abnormality of anxiety disorder, and this will provide new insights into this disease. PMID:25053913

  18. Mitochondrial activity and brain functions during cortical depolarization

    NASA Astrophysics Data System (ADS)

    Mayevsky, Avraham; Sonn, Judith

    2008-12-01

    Cortical depolarization (CD) of the cerebral cortex could be developed under various pathophysiological conditions. In animal models, CD was recorded under partial or complete ischemia as well as when cortical spreading depression (SD) was induced externally or by internal stimulus. The development of CD in patients and the changes in various metabolic parameters, during CD, was rarely reported. Brain metabolic, hemodynamic, ionic and electrical responses to the CD event are dependent upon the O2 balance in the tissue. When the O2 balance is negative (i.e. ischemia), the CD process will be developed due to mitochondrial dysfunction, lack of energy and the inhibition of Na+-K+-ATPase. In contradiction, when oxygen is available (i.e. normoxia) the development of CD after induction of SD will accelerate mitochondrial respiration for retaining ionic homeostasis and normal brain functions. We used the multiparametric monitoring approach that enable real time monitoring of mitochondrial NADH redox state, microcirculatory blood flow and oxygenation, extracellular K+, Ca2+, H+ levels, DC steady potential and electrocorticogram (ECoG). This monitoring approach, provide a unique tool that has a significant value in analyzing the pathophysiology of the brain when SD developed under normoxia, ischemia, or hypoxia. We applied the same monitoring approach to patients suffered from severe head injury or exposed to neurosurgical procedures.

  19. TMJ function after partial condylectomy in active mandibular condylar hyperplasia

    PubMed Central

    Olate, Sergio; Martinez, Felipe; Uribe, Francisca; Pozzer, Leandro; Cavalieri-Pereira, Lucas; de Moraes, Marcio

    2014-01-01

    Condylar hyperplasia is a frequent pathology that causes severe facial asymmetries. The partial condylectomy generally halts the disease. The aim of this research was to examine post-condylectomy TMJ function; 14 patients were included in this study, 6 male and 8 female. The average age was 21 years old. In all, the partial condylectomy was performed with preauricular or endaural access and the osteotomy were performed with drills, saw or an ultrasonic system. The patients were assessed with 3 or more time after surgery and were considering maximum mouth opening, right and left lateralities, presence of pain, noises, alterations in the facial nerve (VII) and esthetic alteration from the scar. The analysis was performed with the visual analog scale (VAS) and with a 7 cm metallic rule. Data analysis was descriptive plus chi-square test considering p value < 0.05 for statistical differences. With an average of 11 month after surgery, the results showed that the open mouth (over 35 mm) and lateralities (average 9 mm for the both right and left side) were normal and without statistical differences between the right or left side. Noise was observed in 3 patients and pain was observed in two patients with level 2 and 1 (VAS score). Scar was not related to problem with patient and the temporal branch of facial nerve was observed with limitations but without problem for patients. It can be concluded that the condylectomy is a safe and effective procedure with low morbidity for patients. PMID:24753777

  20. The Complex Association between Religious Activities and Functional Limitations in Older Adults

    ERIC Educational Resources Information Center

    Hybels, Celia F.; Blazer, Dan G.; George, Linda K.; Koenig, Harold G.

    2012-01-01

    Purpose of the Study: To examine the longitudinal associations between 3 dimensions of religious involvement--religious attendance, use of religious media, and private religious activities--and 3 domains of functional status--limitations in basic activities of daily living (ADL), instrumental activities of daily living (IADL), and mobility in…

  1. Activation and Function of iNKT and MAIT Cells.

    PubMed

    Chandra, Shilpi; Kronenberg, Mitchell

    2015-01-01

    Over the last two decades, it has been established that peptides are not the only antigens recognized by T lymphocytes. Here, we review information on two T lymphocyte populations that recognize nonpeptide antigens: invariant natural killer T cells (iNKT cells), which respond to glycolipids, and mucosal associated invariant T cells (MAIT cells), which recognize microbial metabolites. These two populations have a number of striking properties that distinguish them from the majority of T cells. First, their cognate antigens are presented by nonclassical class I antigen-presenting molecules; CD1d for iNKT cells and MR1 for MAIT cells. Second, these T lymphocyte populations have a highly restricted diversity of their T cell antigen receptor α chains. Third, these cells respond rapidly to antigen or cytokine stimulation by producing copious amounts of cytokines, such as IFNγ, which normally are only made by highly differentiated effector T lymphocytes. Because of their response characteristics, iNKT and MAIT cells act at the interface of innate and adaptive immunity, participating in both types of responses. In this review, we will compare these two subsets of innate-like T cells, with an emphasis on the various ways that lead to their activation and their participation in antimicrobial responses.

  2. Brain temperature fluctuation: a reflection of functional neural activation.

    PubMed

    Kiyatkin, Eugene A; Brown, P Leon; Wise, Roy A

    2002-07-01

    Although it is known that relatively large increases in local brain temperature can occur during behaviour and in response to various novel, stressful and emotionally arousing environmental stimuli, the source of this heat is not clearly established. To clarify this issue, we monitored the temperature in three brain structures (dorsal and ventral striatum, cerebellum) and in arterial blood at the level of the abdominal aorta in freely moving rats exposed to several environmental challenges ranging from traditional stressors to simple sensory stimuli (cage change, tail pinch, exposure to another male rat, a female rat, a mouse or an unexpected sound). We found that brain temperature was consistently higher than arterial blood temperature, and that brain temperature increased prior to, and to a greater extent than, the increase in blood temperature evoked by each test challenge. Thus, the local metabolic consequences of widely correlated neural activity appear to be the primary source of increases in brain temperature and a driving force behind the associated changes in body temperature.

  3. Function Follows Form: Activation of Shape and Function Features during Object Identification

    ERIC Educational Resources Information Center

    Yee, Eiling; Huffstetler, Stacy; Thompson-Schill, Sharon L.

    2011-01-01

    Most theories of semantic memory characterize knowledge of a given object as comprising a set of semantic features. But how does conceptual activation of these features proceed during object identification? We present the results of a pair of experiments that demonstrate that object recognition is a dynamically unfolding process in which function…

  4. Physical activity as an indicator of predictive functional disability in elderly.

    PubMed

    Virtuoso Júnior, Jair Sindra; Tribess, Sheilla; Paulo, Thais Reis Silva De; Martins, Cristiane Alves; Romo-Perez, Vicente

    2012-01-01

    To analyze the time spent on physical activity in female and male individuals as a predictor of the absence of functional disability in older adults, a cross-sectional study was conducted with 624 individuals. Receiver Operating Characteristic curves (ROC) were constructed and compared to areas of physical activity by gender and the absence of functional disability. We identified cutoffs of physical activity (minutes / week) to predict the absence of functional disability (CI 95%). It was found that there is a higher area under the ROC curve for the time spent on physical activities in females. It was observed that 280 minutes / week (women) or 410 minutes / week (men) were the best cutoff points for predicting the absence of functional disability. Time spent on physical activity practices can serve as an important indicator to sort priority groups for certain interventions.

  5. Functional impairment of natural killer cells in active ulcerative colitis: reversion of the defective natural killer activity by interleukin 2.

    PubMed Central

    Manzano, L; Alvarez-Mon, M; Abreu, L; Antonio Vargas, J; de la Morena, E; Corugedo, F; Duràntez, A

    1992-01-01

    We have studied the functional characteristics and clinical importance of the natural killer (NK) cytotoxicity of peripheral blood mononuclear cells (PBMNC) from patients with ulcerative colitis. Normal NK activity was observed in PBMNC from patients with inactive disease, but a pronounced decrease was found in those with active disease. Clinical change from active to inactive disease was associated with enhancement of the depressed NK activity. The impairment of NK cytotoxicity found in patients with active disese could not be ascribed to a deficient number of NK cells as the amounts of HNK-1+, CD16+ (Leu 11), and CD11b (OKM1) cells in PBMNC were within normal ranges. This defective cytotoxic PBMNC activity was normalised by short term (18 hour) incubation with recombinant interleukin 2 (rIL-2). Moreover, long term (5 day) incubation of these effector cells with rIL-2 induced strong cytotoxic activity against NK resistant and NK sensitive target cells in patients with active and inactive disease. We also found that both precursors and effectors of cytotoxic activity promoted by short term and long term incubation with rIL-2 of PBMNC from the patients showed the phenotype of NK cells (CD16+, CD3-). Taken together, these results show that active ulcerative colitis is associated with a defective function of NK cells that is found to be normal in the inactive stage of the disease. The possible pathogenic and therapeutic implications of these findings are discussed. PMID:1541421

  6. The Role of Physical Activity and Physical Function on the Risk of Falls in Older Mexican Americans.

    PubMed

    Lewis, Zakkoyya H; Markides, Kyriakos S; Ottenbacher, Kenneth J; Al Snih, Soham

    2016-07-01

    We investigated the relationship between physical activity and physical function on the risk of falls over time in a cohort of Mexican-American adults aged 75 and older from the Hispanic Established Population for the Epidemiologic Study of the Elderly (H-EPESE). Participants were divided into four groups according to their level of physical activity and physical function: low physical activity and low physical function (n = 453); low physical activity and high physical function (n = 54); high physical activity and low physical function (n = 307); and high physical activity and high physical function (n = 197). Using generalized linear equation estimation, we showed that participants with high physical activity and low physical function had a greater fall risk over time, followed by the high physical activity and high physical function group. Participants seldom took part in activities that improve physical function. To prevent falls, modifications to physical activity should be made for older Mexican Americans.

  7. Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity

    PubMed Central

    Tallner, Alexander; Waschbisch, Anne; Hentschke, Christian; Pfeifer, Klaus; Mäurer, Mathias

    2015-01-01

    Multiple sclerosis (MS) patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36), and Beck Depression Inventory (BDI). We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL). Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF-36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients. PMID:26147422

  8. Metabolites related to gut bacterial metabolism, peroxisome proliferator-activated receptor-alpha activation, and insulin sensitivity are associated with physical function in functionally-limited older adults

    PubMed Central

    Lustgarten, Michael S; Price, Lori L; Chalé, Angela; Fielding, Roger A

    2014-01-01

    Identification of mechanisms underlying physical function will be important for addressing the growing challenge that health care will face with physical disablement in the expanding aging population. Therefore, the goals of the current study were to use metabolic profiling to provide insight into biologic mechanisms that may underlie physical function by examining the association between baseline and the 6-month change in serum mass spectrometry-obtained amino acids, fatty acids, and acylcarnitines with baseline and the 6-month change in muscle strength (leg press one repetition maximum divided by total lean mass, LP/Lean), lower extremity function [short physical performance battery (SPPB)], and mobility (400 m gait speed, 400-m), in response to 6 months of a combined resistance exercise and nutritional supplementation (whey protein or placebo) intervention in functionally-limited older adults (SPPB ≤ 10; 70–85 years, N = 73). Metabolites related to gut bacterial metabolism (cinnamoylglycine, phenol sulfate, p-cresol sulfate, 3-indoxyl sulfate, serotonin, N-methylproline, hydrocinnamate, dimethylglycine, trans-urocanate, valerate) that are altered in response to peroxisome proliferator-activated receptor-alpha (PPAR-α) activation (α-hydroxyisocaproate, α-hydroxyisovalerate, 2-hydroxy-3-methylvalerate, indolelactate, serotonin, 2-hydroxypalmitate, glutarylcarnitine, isobutyrylcarnitine, cinnamoylglycine) and that are related to insulin sensitivity (monounsaturated fatty acids: 5-dodecenoate, myristoleate, palmitoleate; γ-glutamylamino acids: γ-glutamylglutamine, γ-glutamylalanine, γ-glutamylmethionine, γ-glutamyltyrosine; branched-chain amino acids: leucine, isoleucine, valine) were associated with function at baseline, with the 6-month change in function or were identified in backward elimination regression predictive models. Collectively, these data suggest that gut microbial metabolism, PPAR-α activation, and insulin sensitivity may be involved in

  9. Function of reactive oxygen species during animal development: passive or active?

    PubMed

    Covarrubias, Luis; Hernández-García, David; Schnabel, Denhí; Salas-Vidal, Enrique; Castro-Obregón, Susana

    2008-08-01

    Oxidative stress is considered causal of aging and pathological cell death, however, very little is known about its function in the natural processes that support the formation of an organism. It is generally thought that cells must continuously protect themselves from the possible damage caused by reactive oxygen species (ROS) (passive ROS function). However, presently, ROS are recognized as physiologically relevant molecules that mediate cell responses to a variety of stimuli, and the activities of several molecules, some developmentally relevant, are directly or indirectly regulated by oxidative stress (active ROS function). Here we review recent data that are suggestive of specific ROS functions during development of animals, particularly mammals.

  10. Interspecies activity correlations reveal functional correspondence between monkey and human brain areas.

    PubMed

    Mantini, Dante; Hasson, Uri; Betti, Viviana; Perrucci, Mauro G; Romani, Gian Luca; Corbetta, Maurizio; Orban, Guy A; Vanduffel, Wim

    2012-02-05

    Evolution-driven functional changes in the primate brain are typically assessed by aligning monkey and human activation maps using cortical surface expansion models. These models use putative homologous areas as registration landmarks, assuming they are functionally correspondent. For cases in which functional changes have occurred in an area, this assumption prohibits to reveal whether other areas may have assumed lost functions. Here we describe a method to examine functional correspondences across species. Without making spatial assumptions, we assessed similarities in sensory-driven functional magnetic resonance imaging responses between monkey (Macaca mulatta) and human brain areas by temporal correlation. Using natural vision data, we revealed regions for which functional processing has shifted to topologically divergent locations during evolution. We conclude that substantial evolution-driven functional reorganizations have occurred, not always consistent with cortical expansion processes. This framework for evaluating changes in functional architecture is crucial to building more accurate evolutionary models.

  11. Brain functional correlates of working memory: reduced load-modulated activation and deactivation in aging without hyperactivation or functional reorganization.

    PubMed

    Kaup, Allison R; Drummond, Sean P A; Eyler, Lisa T

    2014-10-01

    We aimed to identify brain functional correlates of working memory performance in aging, in hopes of facilitating understanding of mechanisms that promote better versus worse working memory in late-life. Among 64 healthy adults, aged 23 to 78, we examined the relationship between age, working memory performance, and brain functional response during task performance. We focused on the association between working memory load-modulated functional response and individual differences in performance and whether these function-performance relationships differed with age. As expected, older age was associated with poorer working memory performance. Older age was also associated with reduced load-modulated activation including in bilateral prefrontal and parietal regions and left caudate as well as reduced deactivation including in the medial prefrontal cortex. Contrary to findings of hyperactivation in aging, we found no evidence of increased activation with older age. Positive associations identified between brain response and performance did not differ with age. Our findings suggest that the neural mechanisms underlying better versus worse working memory performance are age-invariant across adulthood, and argue against a pattern of functional reorganization in aging. Results are discussed within the broader literature, in which significant heterogeneity in findings between studies has been common.

  12. Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging.

    PubMed

    Voss, Michelle W; Weng, Timothy B; Burzynska, Agnieszka Z; Wong, Chelsea N; Cooke, Gillian E; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P; Olson, Erin A; McAuley, Edward; Kramer, Arthur F

    2016-05-01

    Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the default mode network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks.

  13. Activation and function of human Hageman factor. The role of high molecular weight kininogen and prekallikrein.

    PubMed Central

    Meier, H L; Pierce, J V; Colman, R W; Kaplan, A P

    1977-01-01

    The activation and function of surface-bound Hageman factor in human plasma are dependent upon both high molecular weight (HMW) kininogen and prekallikrein. HMW kininogen does not affect the binding of Hageman factor to surfaces, but it enhances the function of surface-bound Hageman factor as assessed by its ability to activate prekallikrein and Factor XI. The initial conversion of prekallikrein to kallikrein by the surface-bound Hageman factor in the presence of HMW kininogen is followed by a rapid enzymatic activation of Hageman factor by kallikrein. The latter interaction is also facilitated by HMW kininogen. Kallikrein therefore functions as an activator of Hageman factor by a positive feedback mechanism and generates most of the activated Hageman factor during brief exposure of plasma to activating surfaces. HMW kininogen is a cofactor in the enzymatic activation of Hageman factor by kallikrein and it also augments the function of the activated Hageman factor generated. The stoichiometry of the Hagman factor interaction with HMW kininogen suggests that it enhances the activity of the active site of Hageman factor. Since HMW kininogen and prekallikrein circulate as a complex, HMW kininogen may also place the prekallikrein in an optimal position for its reciprocal interaction with Hageman factor to proceed. The surface appears to play a passive role upon which bound Hageman factor and the prekallikrein-HMW kininogen complex can interact. PMID:874082

  14. Trajectory of change in pain, depression, and physical functioning after physical activity adoption in fibromyalgia.

    PubMed

    Steiner, Jennifer L; Bigatti, Silvia M; Ang, Dennis C

    2015-07-01

    Fibromyalgia is associated with widespread pain, depression, and declines in physical functioning. The purpose of this study was to examine the trajectory of these symptoms over time related to physical activity adoption and maintenance via motivational interviewing versus education, to increase physical activity. There were no treatment group differences; we divided the sample (n = 184) based on changes in physical activity. Repeated measures analyses demonstrated differential patterns in depression, pain, and physical functioning at 24 and 36 weeks. Findings suggest increased physical activity may serve as a multiple-target intervention that provides moderate to large, long-lasting benefits for individuals with fibromyalgia.

  15. Preference as a Function of Active Interresponse Times: A Test of the Active Time Model

    ERIC Educational Resources Information Center

    Misak, Paul; Cleaveland, J. Mark

    2011-01-01

    In this article, we describe a test of the active time model for concurrent variable interval (VI) choice. The active time model (ATM) suggests that the time since the most recent response is one of the variables controlling choice in concurrent VI VI schedules of reinforcement. In our experiment, pigeons were trained in a multiple concurrent…

  16. Second-Order Perturbation Theory for Generalized Active Space Self-Consistent-Field Wave Functions.

    PubMed

    Ma, Dongxia; Li Manni, Giovanni; Olsen, Jeppe; Gagliardi, Laura

    2016-07-12

    A multireference second-order perturbation theory approach based on the generalized active space self-consistent-field (GASSCF) wave function is presented. Compared with the complete active space (CAS) and restricted active space (RAS) wave functions, GAS wave functions are more flexible and can employ larger active spaces and/or different truncations of the configuration interaction expansion. With GASSCF, one can explore chemical systems that are not affordable with either CASSCF or RASSCF. Perturbation theory to second order on top of GAS wave functions (GASPT2) has been implemented to recover the remaining electron correlation. The method has been benchmarked by computing the chromium dimer ground-state potential energy curve. These calculations show that GASPT2 gives results similar to CASPT2 even with a configuration interaction expansion much smaller than the corresponding CAS expansion.

  17. Synergistic effect between defect sites and functional groups on the hydrolysis of cellulose over activated carbon.

    PubMed

    Foo, Guo Shiou; Sievers, Carsten

    2015-02-01

    The chemical oxidation of activated carbon by H2 O2 and H2 SO4 is investigated, structural and chemical modifications are characterized, and the materials are used as catalysts for the hydrolysis of cellulose. Treatment with H2 O2 enlarges the pore size and imparts functional groups such as phenols, lactones, and carboxylic acids. H2 SO4 treatment targets the edges of carbon sheets primarily, and this effect is more pronounced with a higher temperature. Adsorption isotherms demonstrate that the adsorption of oligomers on functionalized carbon is dominated by van der Waals forces. The materials treated chemically are active for the hydrolysis of cellulose despite the relative weakness of most of their acid sites. It is proposed that a synergistic effect between defect sites and functional groups enhances the activity by inducing a conformational change in the glucan chains if they are adsorbed at defect sites. This activates the glycosidic bonds for hydrolysis by in-plane functional groups.

  18. Closed-form expressions of some stochastic adapting equations for nonlinear adaptive activation function neurons.

    PubMed

    Fiori, Simone

    2003-12-01

    In recent work, we introduced nonlinear adaptive activation function (FAN) artificial neuron models, which learn their activation functions in an unsupervised way by information-theoretic adapting rules. We also applied networks of these neurons to some blind signal processing problems, such as independent component analysis and blind deconvolution. The aim of this letter is to study some fundamental aspects of FAN units' learning by investigating the properties of the associated learning differential equation systems.

  19. [14C]deoxyglucose labelling of functional activity in the cephalopod central nervous system.

    PubMed

    Novicki, A; Messenger, J B; Budelmann, B U; Terrell, M L; Kadekaro, M

    1992-07-22

    For the first time, the [14C]deoxyglucose radioautographic technique has been successfully used to map physiological activity in cephalopod brains. In unilaterally blinded octopus and cuttlefish, the optic lobe of the deprived side showed a decreased uptake of the labelled tracer. This suggests that the uptake is related to functional activity. The potential of the [14C]deoxyglucose technique as a powerful tool in studying the functional organization of cephalopod brains is discussed.

  20. Exponential stability of delayed and impulsive cellular neural networks with partially Lipschitz continuous activation functions.

    PubMed

    Song, Xueli; Xin, Xing; Huang, Wenpo

    2012-05-01

    The paper discusses exponential stability of distributed delayed and impulsive cellular neural networks with partially Lipschitz continuous activation functions. By relative nonlinear measure method, some novel criteria are obtained for the uniqueness and exponential stability of the equilibrium point. Our method abandons usual assumptions on global Lipschitz continuity, boundedness and monotonicity of activation functions. Our results are generalization and improvement of some existing ones. Finally, two examples and their simulations are presented to illustrate the correctness of our analysis.

  1. Experiences of Habitual Physical Activity in Maintaining Roles and Functioning among Older Adults: A Qualitative Study

    PubMed Central

    Svantesson, Ulla; Willén, Carin

    2016-01-01

    Physically active older adults have reduced risk of functional restrictions and role limitations. Several aspects may interrelate and influence habitual physical activity (PA). However, older adults' own perspectives towards their PA need to be addressed. The aim of this study was to explore the experiences of habitual physical activity in maintaining roles and functioning among older adult Palestinians ≥60 years. Data were collected through in-depth interviews based on a narrative approach. Seventeen participants were recruited (aged 64–84 years). Data were analyzed using a narrative interpretative method. Findings. Three central narratives were identified, “keep moving, stay healthy,” “social connectedness, a motive to stay active,” and “adapting strategies to age-related changes.” Conclusion. Habitual physical activity was perceived as an important factor to maintain functioning and to preserve active roles in older adults. Walking was the most prominent pattern of physical activity and it was viewed as a vital tool to maintain functioning among the older adults. Social connectedness was considered as a contributing factor to the status of staying active. To adapt the process of age-related changes in a context to stay active, the participants have used different adapting strategies, including protective strategy, awareness of own capabilities, and modifying or adopting new roles. PMID:28078141

  2. Increased premotor cortex activation in high functioning autism during action observation.

    PubMed

    Perkins, Tom J; Bittar, Richard G; McGillivray, Jane A; Cox, Ivanna I; Stokes, Mark A

    2015-04-01

    The mirror neuron (MN) hypothesis of autism has received considerable attention, but to date has produced inconsistent findings. Using functional MRI, participants with high functioning autism or Asperger's syndrome were compared to typically developing individuals (n=12 in each group). Participants passively observed hand gestures that included waving, pointing, and grasping. Concerning the MN network, both groups activated similar regions including prefrontal, inferior parietal and superior temporal regions, with the autism group demonstrating significantly greater activation in the dorsal premotor cortex. Concerning other regions, participants with autism demonstrated increased activity in the anterior cingulate and medial frontal gyrus, and reduced activation in calcarine, cuneus, and middle temporal gyrus. These results suggest that during observation of hand gestures, frontal cortex activation is affected in autism, which we suggest may be linked to abnormal functioning of the MN system.

  3. A novel pattern mining approach for identifying cognitive activity in EEG based functional brain networks.

    PubMed

    Thilaga, M; Vijayalakshmi, R; Nadarajan, R; Nandagopal, D

    2016-06-01

    The complex nature of neuronal interactions of the human brain has posed many challenges to the research community. To explore the underlying mechanisms of neuronal activity of cohesive brain regions during different cognitive activities, many innovative mathematical and computational models are required. This paper presents a novel Common Functional Pattern Mining approach to demonstrate the similar patterns of interactions due to common behavior of certain brain regions. The electrode sites of EEG-based functional brain network are modeled as a set of transactions and node-based complex network measures as itemsets. These itemsets are transformed into a graph data structure called Functional Pattern Graph. By mining this Functional Pattern Graph, the common functional patterns due to specific brain functioning can be identified. The empirical analyses show the efficiency of the proposed approach in identifying the extent to which the electrode sites (transactions) are similar during various cognitive load states.

  4. Sedentary behavior and physical activity are independently related to functional fitness in older adults.

    PubMed

    Santos, Diana A; Silva, Analiza M; Baptista, Fátima; Santos, Rute; Vale, Susana; Mota, Jorge; Sardinha, Luís B

    2012-12-01

    The last decades of life have been traditionally viewed as a time of inevitable disease and frailty. Sedentary living and physical activity may influence capacity to perform activities that are needed to maintain physical independence in daily living. A total of 117 males and 195 females, aged 65-103years, were assessed for physical activity and sedentary time with accelerometers and for functional fitness with the Senior Fitness Test battery. Based on the individual scores for each fitness item, a Z-score was created. Associations between functional fitness with sedentary time and moderate-to-vigorous physical activity (MVPA) were analyzed. A negative association was found between the composite Z-score for functional fitness and the sedentary time, even adjusting for MVPA and other confounders. On the other hand, MVPA was positively associated with the composite Z-score for functional fitness, independently of the sedentary time. In conclusion elderly who spend more time in physical activity or less time in sedentary behaviors exhibit improved functional fitness and other confounders. The results reinforce the importance of promoting both the reduction of sedentary behaviors and the increase of MVPA in this age group, as it may interfere at older ages in order to preserve functional fitness and performance of daily functioning tasks.

  5. Physical activity and obesity mediate the association between childhood motor function and adolescents’ academic achievement

    PubMed Central

    Kantomaa, Marko T.; Stamatakis, Emmanuel; Kankaanpää, Anna; Kaakinen, Marika; Rodriguez, Alina; Taanila, Anja; Ahonen, Timo; Järvelin, Marjo-Riitta; Tammelin, Tuija

    2013-01-01

    The global epidemic of obesity and physical inactivity may have detrimental implications for young people’s cognitive function and academic achievement. This prospective study investigated whether childhood motor function predicts later academic achievement via physical activity, fitness, and obesity. The study sample included 8,061 children from the Northern Finland Birth Cohort 1986, which contains data about parent-reported motor function at age 8 y and self-reported physical activity, predicted cardiorespiratory fitness (cycle ergometer test), obesity (body weight and height), and academic achievement (grades) at age 16 y. Structural equation models with unstandardized (B) and standardized (β) coefficients were used to test whether, and to what extent, physical activity, cardiorespiratory fitness, and obesity at age 16 mediated the association between childhood motor function and adolescents’ academic achievement. Physical activity was associated with a higher grade-point average, and obesity was associated with a lower grade-point average in adolescence. Furthermore, compromised motor function in childhood had a negative indirect effect on adolescents’ academic achievement via physical inactivity (B = –0.023, 95% confidence interval = –0.031, –0.015) and obesity (B = –0.025, 95% confidence interval = –0.039, –0.011), but not via cardiorespiratory fitness. These results suggest that physical activity and obesity may mediate the association between childhood motor function and adolescents’ academic achievement. Compromised motor function in childhood may represent an important factor driving the effects of obesity and physical inactivity on academic underachievement. PMID:23277558

  6. Physical activity and obesity mediate the association between childhood motor function and adolescents' academic achievement.

    PubMed

    Kantomaa, Marko T; Stamatakis, Emmanuel; Kankaanpää, Anna; Kaakinen, Marika; Rodriguez, Alina; Taanila, Anja; Ahonen, Timo; Järvelin, Marjo-Riitta; Tammelin, Tuija

    2013-01-29

    The global epidemic of obesity and physical inactivity may have detrimental implications for young people's cognitive function and academic achievement. This prospective study investigated whether childhood motor function predicts later academic achievement via physical activity, fitness, and obesity. The study sample included 8,061 children from the Northern Finland Birth Cohort 1986, which contains data about parent-reported motor function at age 8 y and self-reported physical activity, predicted cardiorespiratory fitness (cycle ergometer test), obesity (body weight and height), and academic achievement (grades) at age 16 y. Structural equation models with unstandardized (B) and standardized (β) coefficients were used to test whether, and to what extent, physical activity, cardiorespiratory fitness, and obesity at age 16 mediated the association between childhood motor function and adolescents' academic achievement. Physical activity was associated with a higher grade-point average, and obesity was associated with a lower grade-point average in adolescence. Furthermore, compromised motor function in childhood had a negative indirect effect on adolescents' academic achievement via physical inactivity (B = -0.023, 95% confidence interval = -0.031, -0.015) and obesity (B = -0.025, 95% confidence interval = -0.039, -0.011), but not via cardiorespiratory fitness. These results suggest that physical activity and obesity may mediate the association between childhood motor function and adolescents' academic achievement. Compromised motor function in childhood may represent an important factor driving the effects of obesity and physical inactivity on academic underachievement.

  7. Task-free presurgical mapping using functional magnetic resonance imaging intrinsic activity

    PubMed Central

    Liu, Hesheng; Buckner, Randy L.; Talukdar, Tanveer; Tanaka, Naoaki; Madsen, Joseph R.; Stufflebeam, Steven M.

    2013-01-01

    Object Low-frequency components of the spontaneous functional MR imaging signal provide information about the intrinsic functional and anatomical organization of the brain. The ability to use such methods in individual patients may provide a powerful tool for presurgical planning. The authors explore the feasibility of presurgical motor function mapping in which a task-free paradigm is used. Methods Six surgical candidates with tumors or epileptic foci near the motor cortex participated in this study. The investigators directly compared task-elicited activation of the motor system to activation obtained from intrinsic activity correlations. The motor network within the unhealthy hemisphere was identified based on intrinsic activity correlations, allowing distortions of functional anatomy caused by the tumor and epilepsy to be directly visualized. The precision of the motor function mapping was further explored in 1 participant by using direct cortical stimulation. Results The motor regions localized based on the spontaneous activity correlations were quite similar to the regions defined by actual movement tasks and cortical stimulation. Using intrinsic activity correlations, it was possible to map the motor cortex in presurgical patients. Conclusions This task-free paradigm may provide a powerful approach to map functional anatomy in patients without task compliance and allow multiple brain systems to be determined in a single scanning session. PMID:19361264

  8. Dynamical Behaviors of Multiple Equilibria in Competitive Neural Networks With Discontinuous Nonmonotonic Piecewise Linear Activation Functions.

    PubMed

    Nie, Xiaobing; Zheng, Wei Xing

    2016-03-01

    This paper addresses the problem of coexistence and dynamical behaviors of multiple equilibria for competitive neural networks. First, a general class of discontinuous nonmonotonic piecewise linear activation functions is introduced for competitive neural networks. Then based on the fixed point theorem and theory of strict diagonal dominance matrix, it is shown that under some conditions, such n -neuron competitive neural networks can have 5(n) equilibria, among which 3(n) equilibria are locally stable and the others are unstable. More importantly, it is revealed that the neural networks with the discontinuous activation functions introduced in this paper can have both more total equilibria and locally stable equilibria than the ones with other activation functions, such as the continuous Mexican-hat-type activation function and discontinuous two-level activation function. Furthermore, the 3(n) locally stable equilibria given in this paper are located in not only saturated regions, but also unsaturated regions, which is different from the existing results on multistability of neural networks with multiple level activation functions. A simulation example is provided to illustrate and validate the theoretical findings.

  9. Alterations in Brain Activation During Cognitive Empathy Are Related to Social Functioning in Schizophrenia

    PubMed Central

    Smith, Matthew J.; Schroeder, Matthew P.; Abram, Samantha V.; Goldman, Morris B.; Parrish, Todd B.; Wang, Xue; Derntl, Birgit; Habel, Ute; Decety, Jean; Reilly, James L.; Csernansky, John G.; Breiter, Hans C.

    2015-01-01

    Impaired cognitive empathy (ie, understanding the emotional experiences of others) is associated with poor social functioning in schizophrenia. However, it is unclear whether the neural activity underlying cognitive empathy relates to social functioning. This study examined the neural activation supporting cognitive empathy performance and whether empathy-related activation during correctly performed trials was associated with self-reported cognitive empathy and measures of social functioning. Thirty schizophrenia outpatients and 24 controls completed a cognitive empathy paradigm during functional magnetic resonance imaging. Neural activity corresponding to correct judgments about the expected emotional expression in a social interaction was compared in schizophrenia subjects relative to control subjects. Participants also completed a self-report measure of empathy and 2 social functioning measures (social competence and social attainment). Schizophrenia subjects demonstrated significantly lower accuracy in task performance and were characterized by hypoactivation in empathy-related frontal, temporal, and parietal regions as well as hyperactivation in occipital regions compared with control subjects during accurate cognitive empathy trials. A cluster with peak activation in the supplementary motor area (SMA) extending to the anterior midcingulate cortex (aMCC) correlated with social competence and social attainment in schizophrenia subjects but not controls. These results suggest that neural correlates of cognitive empathy may be promising targets for interventions aiming to improve social functioning and that brain activation in the SMA/aMCC region could be used as a biomarker for monitoring treatment response. PMID:24583906

  10. Alterations in brain activation during cognitive empathy are related to social functioning in schizophrenia.

    PubMed

    Smith, Matthew J; Schroeder, Matthew P; Abram, Samantha V; Goldman, Morris B; Parrish, Todd B; Wang, Xue; Derntl, Birgit; Habel, Ute; Decety, Jean; Reilly, James L; Csernansky, John G; Breiter, Hans C

    2015-01-01

    Impaired cognitive empathy (ie, understanding the emotional experiences of others) is associated with poor social functioning in schizophrenia. However, it is unclear whether the neural activity underlying cognitive empathy relates to social functioning. This study examined the neural activation supporting cognitive empathy performance and whether empathy-related activation during correctly performed trials was associated with self-reported cognitive empathy and measures of social functioning. Thirty schizophrenia outpatients and 24 controls completed a cognitive empathy paradigm during functional magnetic resonance imaging. Neural activity corresponding to correct judgments about the expected emotional expression in a social interaction was compared in schizophrenia subjects relative to control subjects. Participants also completed a self-report measure of empathy and 2 social functioning measures (social competence and social attainment). Schizophrenia subjects demonstrated significantly lower accuracy in task performance and were characterized by hypoactivation in empathy-related frontal, temporal, and parietal regions as well as hyperactivation in occipital regions compared with control subjects during accurate cognitive empathy trials. A cluster with peak activation in the supplementary motor area (SMA) extending to the anterior midcingulate cortex (aMCC) correlated with social competence and social attainment in schizophrenia subjects but not controls. These results suggest that neural correlates of cognitive empathy may be promising targets for interventions aiming to improve social functioning and that brain activation in the SMA/aMCC region could be used as a biomarker for monitoring treatment response.

  11. The Geriatric Hand: Correlation of Hand-Muscle Function and Activity Restriction in Elderly

    ERIC Educational Resources Information Center

    Incel, Nurgul Arinci; Sezgin, Melek; As, Ismet; Cimen, Ozlem Bolgen; Sahin, Gunsah

    2009-01-01

    On the basis of the importance of hand manipulation in activities of daily living (ADL), deterioration of hand function because of various factors reduces quality and independence of life of the geriatric population. The aim of this study was to identify age-induced changes in manual function and to quantify the correlations between hand-muscle…

  12. Some Problems for Representations of Brain Organization Based on Activation in Functional Imaging

    ERIC Educational Resources Information Center

    Sidtis, John J.

    2007-01-01

    Functional brain imaging has overshadowed traditional lesion studies in becoming the dominant approach to the study of brain-behavior relationships. The proponents of functional imaging studies frequently argue that this approach provides an advantage over lesion studies by observing normal brain activity in vivo without the disruptive effects of…

  13. Brain Activation during Semantic Processing in Autism Spectrum Disorders via Functional Magnetic Resonance Imaging

    ERIC Educational Resources Information Center

    Harris, Gordon J.; Chabris, Christopher F.; Clark, Jill; Urban, Trinity; Aharon, Itzhak; Steele, Shelley; McGrath, Lauren; Condouris, Karen; Tager-Flusberg, Helen

    2006-01-01

    Language and communication deficits are core features of autism spectrum disorders (ASD), even in high-functioning adults with ASD. This study investigated brain activation patterns using functional magnetic resonance imaging in right-handed adult males with ASD and a control group, matched on age, handedness, and verbal IQ. Semantic processing in…

  14. Giving meaning to measure: linking self-reported fatigue and function to performance of everyday activities.

    PubMed

    Mallinson, Trudy; Cella, David; Cashy, John; Holzner, Bernhard

    2006-03-01

    Fatigue, a common symptom of cancer patients, particularly those on active treatment, is generally evaluated using self-report methods, yet it remains unclear how self-reported fatigue scores relate to performance of daily activities. This study examines the relationships among self-reported and performance-based measures of function in patients receiving chemotherapy (CT) to link self-reported fatigue measures to self-report and performance-based measures of function. Self-reported fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and self-reported physical function using the physical function 10 subscale of the Short Form 36 (SF-36) (PF-10) were measured in 64 patients within 2 weeks of beginning CT (n=64) and after three cycles of CT (n=48). Motor and cognitive functions were captured using five self-reported and seven observed-performance measures at each time point. Significant correlations between self-reported and observed measures ranged from 0.30 to 0.71. Self-reported fatigue correlated (0.30-0.45) with performance-based function. FACIT-F scores in the range of 30 and below and PF-10 scores in the range of 50 and below were related to an increased difficulty performing everyday activities. Observed measures of physical performance correlate moderately with self-reported fatigue and self-reported physical function. These relationships enable one to begin linking fatigue scores directly to a person's ability to perform everyday activities.

  15. A Physical Activity Program Improves Behavior and Cognitive Functions in Children with ADHD: An Exploratory Study

    ERIC Educational Resources Information Center

    Verret, Claudia; Guay, Marie-Claude; Berthiaume, Claude; Gardiner, Phillip; Beliveau, Louise

    2012-01-01

    Objective: The objective of this study is to explore the effects of a moderate- to high-intensity physical activity program on fitness, cognitive functions, and ADHD-related behavior in children with ADHD. Method: Fitness level, motor skills, behaviors, and cognitive functions are assessed by standardized tests before and after a 10-week training…

  16. trans-Platinum(II) complex of 3-aminoflavone - synthesis, X-ray crystal structure and biological activities in vitro.

    PubMed

    Fabijańska, Małgorzata; Studzian, Kazimierz; Szmigiero, Leszek; Rybarczyk-Pirek, Agnieszka J; Pfitzner, Arno; Cebula-Obrzut, Barbara; Smolewski, Piotr; Zyner, Elżbieta; Ochocki, Justyn

    2015-01-21

    This paper describes the synthesis of trans-bis-(3-aminoflavone)dichloridoplatinum(ii) (trans-Pt(3-af)2Cl2; TCAP) for use as a potential anticancer compound, and the evaluation of its structure by elemental and spectral analyses, and X-ray crystallography. The complex demonstrated a significant cytotoxic effect against human and murine cancer cell lines, as well as weaker toxicity towards healthy cells (human peripheral blood lymphocytes) in comparison with cisplatin. Various biochemical and morphological methods confirm that the proapoptotic activity of trans-Pt(3-af)2Cl2 is markedly higher than the reference cisplatin. Our results suggest that trans-Pt(3-af)2Cl2 may have a different antitumour specificity from that of cisplatin.

  17. Cross-sectional imaging of functional activation in the rat somatosensory cortex with optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Aguirre, A. D.; Chen, Y.; Ruvinskaya, L.; Devor, A.; Boas, D. A.; Fujimoto, J. G.

    2005-08-01

    Simultaneous optical coherence tomography (OCT) and video microscopy were performed on the rat somatosensory cortex through a thinned skull during forepaw stimulation. Fractional change measurements in OCT images reveal a functional signal timecourse similar to well understood hemodynamic signal timecourses measured with video microscopy. The precise etiology of the observed OCT functional signal is still under investigation, but these results suggest that OCT can provide high-resolution cross-sectional images of functional neuro-vascular activation.

  18. Functional activation of lymphocyte CD44 in peripheral blood is a marker of autoimmune disease activity.

    PubMed Central

    Estess, P; DeGrendele, H C; Pascual, V; Siegelman, M H

    1998-01-01

    Interactions between complementary receptors on leukocytes and endothelial cells play a central role in regulating extravasation from the blood and thereby affect both normal and pathologic inflammatory responses. CD44 on lymphocytes that has been "activated" to bind its principal ligand hyaluronate (HA) on endothelium can mediate the primary adhesion (rolling) of lymphocytes to vascular endothelial cells under conditions of physiologic shear stress, and this interaction is used for activated T cell extravasation into an inflamed site in vivo in mice (DeGrendele, H.C., P. Estess, L.J. Picker, and M.H. Siegelman. 1996. J. Exp. Med. 183:1119-1130. DeGrendele, H.D., P. Estess, and M.H. Siegelman. 1997. Science. 278:672-675. DeGrendele, H.C., P. Estess, and M.H. Siegelman. 1997. J. Immunol. 159: 2549-2553). Here, we have investigated the role of lymphocyte-borne-activated CD44 in the human and show that CD44-dependent primary adhesion is induced in human peripheral blood T cells through T cell receptor triggering. In addition, lymphocytes capable of CD44/HA-dependent rolling interactions can be found resident within inflamed tonsils. In analysis of peripheral bloods of patients from a pediatric rheumatology clinic, examining systemic lupus erythematosus, and a group of chronic arthropathies, expression of CD44-dependent primary adhesion strongly correlates with concurrent symptomatic disease, with 85% of samples from clinically active patients showing elevated levels of rolling activity (compared with only 4% of inactive patients). These rolling interactions are predominantly mediated by T cells. The results suggest that circulating T lymphocytes bearing activated CD44 are elevated under conditions of chronic inflammation and that these may represent a pathogenically important subpopulation of activated circulating cells that may provide a reliable marker for autoimmune or chronic inflammatory disease activity. PMID:9739051

  19. Functional Specificity of the Visual Word Form Area: General Activation for Words and Symbols but Specific Network Activation for Words

    ERIC Educational Resources Information Center

    Reinke, Karen; Fernandes, Myra; Schwindt, Graeme; O'Craven, Kathleen; Grady, Cheryl L.

    2008-01-01

    The functional specificity of the brain region known as the Visual Word Form Area (VWFA) was examined using fMRI. We explored whether this area serves a general role in processing symbolic stimuli, rather than being selective for the processing of words. Brain activity was measured during a visual 1-back task to English words, meaningful symbols…

  20. Does quadriceps neuromuscular activation capability explain mobility function among older men and women?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related impairment of neuromuscular activation has been shown to contribute to weakness in older adults. However, it is unclear to what extent impaired neuromuscular activation independently accounts for decline of mobility function. The hypothesis of this study is that capability to produce rap...

  1. Does neuromuscular activation capability explain mobility function among older men and women?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related impairment of neuromuscular activation has been shown to contribute to weakness in older adults. However, it is unclear to what extent impaired neuromuscular activation independently accounts for decline of mobility function. The hypothesis of this study is that capability to produce rap...

  2. Participation in Daily Activities of Young Adults with High Functioning Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    McCollum, Mary; LaVesser, Patti; Berg, Christine

    2016-01-01

    Young adults with an autism spectrum disorder (ASD) struggle to assume adult roles. This research assessed the feasibility of using the Adolescent and Young Adult Activity Card Sort (AYA-ACS) with emerging adults with high functioning ASD. Two phases were utilized during this research: (1) comparing the activity participation reported by emerging…

  3. Relation of Physical Activity to Memory Functioning in Older Adults: The Memory Workout Program.

    ERIC Educational Resources Information Center

    Rebok, George W.; Plude, Dana J.

    2001-01-01

    The Memory Workout, a CD-ROM program designed to help older adults increase changes in physical and cognitive activity influencing memory, was tested with 24 subjects. Results revealed a significant relationship between exercise time, exercise efficacy, and cognitive function, as well as interest in improving memory and physical activity.…

  4. IMPORTANCE OF ACTIVATED CARBON'S OXYGEN SURFACE FUNCTIONAL GROUPS ON ELEMENTAL MERCURY ADSORPTION

    EPA Science Inventory

    The effect of varying physical and chemical properties of activated carbons on adsorption of elemental mercury [Hg(0)] was studied by treating two activated carbons to modify their surface functional groups and pore structures. Heat treatment (1200 K) in nitrogen (N2), air oxidat...

  5. Enhancing Preschoolers' Executive Functions through Embedding Cognitive Activities in Shared Book Reading

    ERIC Educational Resources Information Center

    Howard, S. J.; Powell, T.; Vasseleu, E.; Johnstone, S.; Melhuish, E.

    2017-01-01

    Given evidence that early executive functioning sets the stage for a broad range of subsequent outcomes, researchers have sought to identify ways to foster these cognitive capacities. The current series of studies sought to design, develop, and provide evidence for the efficacy of embedding cognitive activities in a commonplace activity--shared…

  6. [On mechanism of functional changes in the organism of teenagers at different levels of locomotor activity].

    PubMed

    Mindubaeva, F A; Shukurov, F A; Salikhova, Y Y; Niyazova, Y I; Ramazanov, A K

    2015-02-01

    Comprehensive study of the cardiovascular system functional condition of 15-16 teenagers while in normal daily locomotor activity and in the mode of regular moderate physical activity was performed. The features of cerebral circulation and myocardium functional condition of teenagers are studied depending on initial tonus of the autonomic nervous system and locomotor activity level in the process of continuous step physical activity on tredmil. The condition of regulatory mechanisms, providing adaptation of teenagers in the conditions of modern school was studied. Research results showed, that elasticity of cerebrum arterial vessels, veins tone, venous outflow for teenagers not having regular physical activity, considerably mionectic. More adequate reaction of coronary blood flow in the process of physical activity is educed for the trained teenagers with the balanced autonomic regulation of cardiac rhythm. This group showed a higher level and regulation quality of organism reserve possibilities.

  7. Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity.

    PubMed

    Pietra, Gabriella; Manzini, Claudia; Rivara, Silvia; Vitale, Massimo; Cantoni, Claudia; Petretto, Andrea; Balsamo, Mirna; Conte, Romana; Benelli, Roberto; Minghelli, Simona; Solari, Nicola; Gualco, Marina; Queirolo, Paola; Moretta, Lorenzo; Mingari, Maria Cristina

    2012-03-15

    Natural killer (NK) cells play a key role in tumor immune surveillance. However, adoptive immunotherapy protocols using NK cells have shown limited clinical efficacy to date, possibly due to tumor escape mechanisms that inhibit NK cell function. In this study, we analyzed the effect of coculturing melanoma cells and NK cells on their phenotype and function. We found that melanoma cells inhibited the expression of major NK receptors that trigger their immune function, including NKp30, NKp44, and NKG2D, with consequent impairment of NK cell-mediated cytolytic activity against various melanoma cell lines. This inhibitory effect was primarily mediated by indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2). Together, our findings suggest that immunosuppressive barriers erected by tumors greatly hamper the antitumor activity of human NK cells, thereby favoring tumor outgrowth and progression.

  8. The geriatric hand: correlation of hand-muscle function and activity restriction in elderly.

    PubMed

    Incel, Nurgul Arinci; Sezgin, Melek; As, Ismet; Cimen, Ozlem Bolgen; Sahin, Gunsah

    2009-09-01

    On the basis of the importance of hand manipulation in activities of daily living (ADL), deterioration of hand function because of various factors reduces quality and independence of life of the geriatric population. The aim of this study was to identify age-induced changes in manual function and to quantify the correlations between hand-muscle function and activity restriction in the geriatric age group, through grip and pinch measurements and a set of questionnaires. Twenty-four geriatric (aged 65-79 years) volunteers participated in the study. Bilateral grip and pinch strengths have been recorded. To document impairment of manual functions, self-estimated hand function, Duruöz and Dreiser hand indices, Geriatrics-Arthritis Impact Measurement Scale (GERI-AIMS) manual dexterity questionnaires have been completed. Activity restriction and quality of life of these patients were inquired with short form (SF)-36 and Instrumental Activities of Daily Living (IADL) scores. Grip and pinch strengths correlated best with Duruöz and Dreiser indices. Similarly, SF-36 and IADL had higher correlation coefficients for Duruöz and Dreiser indices. A very good correlation between IADL and SF-36 was calculated too. Male and female participants revealed statistically significant differences for grip and pinch strengths as well as self-estimated hand function and SF-36. Another result was that none of our parameters, including grip strength and SF-36 had differed significantly between the 65-70 and 70-79 years age subgroups. However, grip strength displayed statistically significant lower values when compared with young adult mean values of a previous study. Our data in this study support the hypothesis that hand-muscle function correlates with functional dependency in the elderly. Manual function can be determined by grip strength in addition to multiple available functional tools. In this study, Dreiser and Duruöz hand function indices were the best to correlate with ADL and

  9. Physical Function and Physical Activity in Obese Adults After Total Knee Arthroplasty.

    PubMed

    Smith, Webb A; Zucker-Levin, Audrey; Mihalko, William M; Williams, Michael; Loftin, Mark; Gurney, James G

    2017-04-01

    Obese patients are more likely to have osteoarthritis and total knee arthroplasty (TKA). This investigation sought to evaluate physical function, activity level, and quality of life (QOL). Obese participants near 1-year postsurgical follow-up appointment were recruited. Evaluation included QOL and activity questionnaire, medical histories, anthropometrics, strength, and aerobic capacity. Sixty participants completed assessments. Obese TKA patients have physical performance limitations and low physical activity levels 1 year after surgery and completion of postoperative rehabilitation.

  10. In Vitro Evaluation of the Apoptosis Function in Human Activated T Cells.

    PubMed

    Magerus-Chatinet, Aude; Rieux-Laucat, Frédéric

    2017-01-01

    The apoptosis function can be monitored on human lymphocytes by quantifying the induced-death upon apoptotic stimuli involving either the extrinsic or the intrinsic pathway on in vitro activated T cells. Her, we describe an in vitro assay allowing the monitoring of three different apoptosis pathways: (1) the FAS-induced pathway, (2) the activation-induced cell death (AICD), and (3) the death induced by starvation of the cells, called activated-cell autonomous death (ACAD).

  11. Effects of immunomodulators on functional activity of innate immunity cells infected with Streptococcus pneumoniae.

    PubMed

    Plekhova, N G; Kondrashova, N M; Somova, L M; Drobot, E I; Lyapun, I N

    2015-02-01

    Low activity of bactericidal enzymes was found in innate immunity cells infected with S. pneumonia. The death of these cells was fastened under these conditions. On the contrary, treatment with antibiotic maxifloxacin was followed by an increase in activity of bactericidal enzymes in phagocytes and induced their death via necrosis. Analysis of the therapeutic properties of immunomodulators tinrostim and licopid in combination with maxifloxacin showed that these combinations correct functional activity of cells infected with S. pneumonia.

  12. Does increased physical activity in school affect children's executive function and aerobic fitness?

    PubMed

    Kvalø, S E; Bru, E; Brønnick, K; Dyrstad, S M

    2017-02-16

    This study seeks to explore whether increased PA in school affects children's executive function and aerobic fitness. The "Active school" study was a 10-month randomized controlled trial. The sample included 449 children (10-11 years old) in five intervention and four control schools. The weekly interventions were 2×45 minutes physically active academic lessons, 5×10 minutes physically active breaks, and 5×10 minutes physically active homework. Aerobic fitness was measured using a 10-minute interval running test. Executive function was tested using four cognitive tests (Stroop, verbal fluency, digit span, and Trail Making). A composite score for executive function was computed and used in analyses. Mixed ANCOVA repeated measures were performed to analyze changes in scores for aerobic fitness and executive function. Analysis showed a tendency for a time×group interaction on executive function, but the results were non-significant F(1, 344)=3.64, P=.057. There was no significant time×group interaction for aerobic fitness. Results indicate that increased physical activity in school might improve children's executive function, even without improvement in aerobic fitness, but a longer intervention period may be required to find significant effects.

  13. Preparation of sodium dodecyl sulphate-functionalized activated carbon from Gnetum gnemon shell for dye adsorption

    NASA Astrophysics Data System (ADS)

    Fatimah, Is; Yahya, Amri; Sasti, Rilis Akista Tria

    2017-03-01

    Preparation of functionalized activated carbon from Gnetum gnemon shell was investigated. This work aimed to prepare highly active adsorbent for dye adsorption process by carbonization of Gnetum gnemon shell followed by functionalization using sodium dodecyl sulphate (SDS) to form SDS-modified activated carbon (SDS-AC). The study of physicochemical character change was performed by SEM and FTIR analysis while the adsorptivity of the materials was tested in methylene blue adsorption. According to the results, it is found that SDS-AC exhibits the greater adsorptivity compared to AC.

  14. New insights into the multidimensional concept of macrophage ontogeny, activation and function.

    PubMed

    Ginhoux, Florent; Schultze, Joachim L; Murray, Peter J; Ochando, Jordi; Biswas, Subhra K

    2016-01-01

    Macrophages have protective roles in immunity to pathogens, tissue development, homeostasis and repair following damage. Maladaptive immunity and inflammation provoke changes in macrophage function that are causative of disease. Despite a historical wealth of knowledge about macrophages, recent advances have revealed unknown aspects of their development and function. Following development, macrophages are activated by diverse signals. Such tissue microenvironmental signals together with epigenetic changes influence macrophage development, activation and functional diversity, with consequences in disease and homeostasis. We discuss here how recent discoveries in these areas have led to a multidimensional concept of macrophage ontogeny, activation and function. In connection with this, we also discuss how technical advances facilitate a new roadmap for the isolation and analysis of macrophages at high resolution.

  15. Psychometric Evaluation of the Physical Activity Enjoyment Scale in Adults with Functional Limitations.

    PubMed

    Murrock, Carolyn J; Bekhet, Abir; Zauszniewski, Jaclene A

    2016-01-01

    Enjoyment is an important construct for understanding physical activity participation, and it has not been examined in adults with functional limitations. This secondary analysis reported the reliability and validity of the Physical Activity Enjoyment Scale (PACES) in a convenience sample of 40 adults with functional limitations. The participants completed the PACES, Center for Epidemiological Studies Depression Scale (CES-D), and the Late Life Function and Disability Instrument (LLFDI) prior to beginning a 12-week feasibility dance intervention study. Results indicated reliability as Cronbach's alpha was .95 and mean inter-item correlation was .52. To further support reliability, homogeneity of the instrument was evaluated using item-to-total scale correlations. Homogeneity was supported as all items had corrected item-to-total correlations greater than .30. For validity, the PACES was significantly related to only the Physical Function component of the LLFDI (r = .38, p = .02), but not the CES-D. Exploratory factor analysis revealed a 3-factor structure that accounted for 73.76% of the variance. This feasibility intervention dance study represented the first attempt to examine the psychometric properties of the PACES in adults with functional limitations. The findings demonstrate support for the scale's reliability and validity among adults with functional limitations. Results are informative as further psychometric testing of the PACES is recommended using randomized clinical trials with larger sample sizes. Enjoyment for physical activity is an important construct for understanding physical activity participation in adults with functional limitations.

  16. Activity-driven local ATP synthesis is required for synaptic function

    PubMed Central

    Rangaraju, Vidhya; Calloway, Nathaniel; Ryan, Timothy A.

    2014-01-01

    Summary Cognitive function is tightly related to metabolic state but the locus of this control is not well understood. Synapses are thought to present large ATP demands however it is unclear how fuel availability and electrical activity impact synaptic ATP levels, and how ATP availability controls synaptic function. We developed a quantitative genetically-encoded optical reporter of presynaptic ATP, Syn-ATP, and find that electrical activity imposes large metabolic demands that are met via activity-driven control of both glycolysis and mitochondrial function. We discovered that the primary source of activity-driven metabolic demand is the synaptic vesicle cycle. In metabolically intact synapses, activity-driven ATP synthesis is well matched to the energetic needs of synaptic function which at steady state results in ~ 106 free ATPs per nerve terminal. Despite this large reservoir of ATP we find that several key aspects of presynaptic function are severely impaired following even brief interruptions in activity-stimulated ATP synthesis. PMID:24529383

  17. Identifying the functional contribution of the defatty-acylase activity of SIRT6

    PubMed Central

    Zhang, Xiaoyu; Khan, Saba; Jiang, Hong; Antonyak, Marc A.; Chen, Xiao; Spiegelman, Nicole A.; Shrimp, Jonathan H.; Cerione, Richard A.; Lin, Hening

    2016-01-01

    Mammalian sirtuin 6 (SIRT6) exhibits many pivotal functions and multiple enzymatic activities, but the contribution of each activity to the various functions is unclear. We identified a SIRT6 G60A mutant that possesses efficient defatty-acylase activity, but has significantly decreased deacetylase activity in vitro and no detectable deacetylase activity in cells. The G60A mutant has decreased ability to bind NAD+, but the presence of fatty-acyl lysine peptides restores NAD+ binding, explaining the retention of the defatty-acylase activity. Using this mutant, we found that SIRT6’s defatty-acylase activity regulates the secretion of numerous proteins. Interestingly, many ribosomal proteins were secreted via exosomes from Sirt6 KO mouse embryonic fibroblasts, and these exosomes increased NIH 3T3 cell proliferation compared with control exosomes. Our data supports that distinct activities of SIRT6 regulate different pathways, and that the G60A mutant is a useful tool to study the contribution of the defatty-acylase activity to SIRT6’s various functions. PMID:27322069

  18. Acute Cognitively Engaging Exergame-Based Physical Activity Enhances Executive Functions in Adolescents

    PubMed Central

    Heinks, Theda; Eggenberger, Noëmi; Schmidt, Mirko

    2016-01-01

    The study aimed to elucidate the influence of cognitive engagement comprised in an acute bout of exergame-based physical activity on executive functions (inhibition, cognitive flexibility) in adolescents. Therefore, the level of cognitive engagement and the intensity of physical activity were systematically varied across three experimental conditions. Sixty-five healthy male adolescents (13–16 years) were randomly assigned to one of three conditions: (a) physical activity with high levels of cognitive engagement during active video gaming, (b) physical activity with low levels of cognitive engagement during active video gaming, (c) sedentary with low levels of cognitive engagement during passive video watching. Manipulation checks, including subjective and objective operationalizations of cognitive engagement, were applied. Executive functions were assessed before and after each condition using the D-KEFS design fluency test. Results showed that cognitive engagement, operationalized by subjects’ ratings and heart rate variability, differed between conditions. The physical activity condition with a high level of cognitive engagement resulted in significantly better performance in cognitive flexibility compared to conditions with low levels of cognitive engagement. Regarding benefits for executive functions in male adolescents, the results indicate that acute physical activity with high cognitive engagement could be more efficient than physical activity of the same intensity with low cognitive engagement. Even though further evidence is needed, these results extend previous research and suggest a methodological approach for measuring cognitive engagement. PMID:28030542

  19. Application of neural networks with orthogonal activation functions in control of dynamical systems

    NASA Astrophysics Data System (ADS)

    Nikolić, Saša S.; Antić, Dragan S.; Milojković, Marko T.; Milovanović, Miroslav B.; Perić, Staniša Lj.; Mitić, Darko B.

    2016-04-01

    In this article, we present a new method for the synthesis of almost and quasi-orthogonal polynomials of arbitrary order. Filters designed on the bases of these functions are generators of generalised quasi-orthogonal signals for which we derived and presented necessary mathematical background. Based on theoretical results, we designed and practically implemented generalised first-order (k = 1) quasi-orthogonal filter and proved its quasi-orthogonality via performed experiments. Designed filters can be applied in many scientific areas. In this article, generated functions were successfully implemented in Nonlinear Auto Regressive eXogenous (NARX) neural network as activation functions. One practical application of the designed orthogonal neural network is demonstrated through the example of control of the complex technical non-linear system - laboratory magnetic levitation system. Obtained results were compared with neural networks with standard activation functions and orthogonal functions of trigonometric shape. The proposed network demonstrated superiority over existing solutions in the sense of system performances.

  20. Functionalization of nanofibrillated cellulose with silver nanoclusters: fluorescence and antibacterial activity.

    PubMed

    Díez, Isabel; Eronen, Paula; Österberg, Monika; Linder, Markus B; Ikkala, Olli; Ras, Robin H A

    2011-09-09

    Native cellulose nanofibers are functionalized using luminescent metal nanoclusters to form a novel type of functional nanocellulose/nanocluster composite. Previously, various types of cellulose fibers have been functionalized with large, non-luminescent metal nanoparticles. Here, mechanically strong native cellulose nanofibers, also called nanofibrillatedcellulose (NFC), microfibrillatedcellulose (MFC) ornanocellulose, disintegrated from macroscopic cellulose pulp fibers are used as support for small and fluorescent silver nanoclusters. The functionalization occurs in a supramolecular manner, mediated by poly(methacrylic acid) that protects nanoclusters while it allows hydrogen bonding with cellulose, leading to composites with fluorescence and antibacterial activity.

  1. Radiomic Texture Analysis Mapping Predicts Areas of True Functional MRI Activity

    PubMed Central

    Hassan, Islam; Kotrotsou, Aikaterini; Bakhtiari, Ali Shojaee; Thomas, Ginu A.; Weinberg, Jeffrey S.; Kumar, Ashok J.; Sawaya, Raymond; Luedi, Markus M.; Zinn, Pascal O.; Colen, Rivka R.

    2016-01-01

    Individual analysis of functional Magnetic Resonance Imaging (fMRI) scans requires user-adjustment of the statistical threshold in order to maximize true functional activity and eliminate false positives. In this study, we propose a novel technique that uses radiomic texture analysis (TA) features associated with heterogeneity to predict areas of true functional activity. Scans of 15 right-handed healthy volunteers were analyzed using SPM8. The resulting functional maps were thresholded to optimize visualization of language areas, resulting in 116 regions of interests (ROIs). A board-certified neuroradiologist classified different ROIs into Expected (E) and Non-Expected (NE) based on their anatomical locations. TA was performed using the mean Echo-Planner Imaging (EPI) volume, and 20 rotation-invariant texture features were obtained for each ROI. Using forward stepwise logistic regression, we built a predictive model that discriminated between E and NE areas of functional activity, with a cross-validation AUC and success rate of 79.84% and 80.19% respectively (specificity/sensitivity of 78.34%/82.61%). This study found that radiomic TA of fMRI scans may allow for determination of areas of true functional activity, and thus eliminate clinician bias. PMID:27151623

  2. Functional fitness and physical activity of Portuguese community-residing older adults.

    PubMed

    Gouveia, Élvio R; Maia, José A; Beunen, Gaston P; Blimkie, Cameron J; Fena, Ercília M; Freitas, Duarte L

    2013-01-01

    The purposes of this study were to generate functional-fitness norms for Portuguese older adults, to determine age and sex differences, and to analyze the physical activity-associated variation in functional fitness. The sample was composed of 802 older adults, 401 men and 401 women, age 60-79 yr. Functional fitness was assessed using the Senior Fitness Test. Physical activity level was estimated via the Baecke questionnaire. The P50 values decreased from 60 to 64 to 75 to 79 yr of age. A significant main effect for age group was found in all functional-fitness tests. Men scored significantly better than women in the chair stand, 8-ft up-and-go, and 6-min walk. Women scored significantly better than men in chair sit-and-reach and back scratch. Active participants scored better in functional-fitness tests than their average and nonactive peers. This study showed a decline in functional fitness with age, better performance of men, and increased proficiency in active participants.

  3. Functions of delay-period activity in the prefrontal cortex and mnemonic scotomas revisited

    PubMed Central

    Funahashi, Shintaro

    2015-01-01

    Working memory (WM) is one of key concepts to understand functions of the prefrontal cortex. Delay-period activity is an important neural correlate to understand the role of WM in prefrontal functions. The importance of delay-period activity is that this activity can encode not only visuospatial information but also a variety of information including non-spatial visual features, auditory and tactile stimuli, task rules, expected reward, and numerical quantity. This activity also participates in a variety of information processing including sensory-to-motor information transformation. These mnemonic features of delay-period activity enable to perform various important operations that the prefrontal cortex participates in, such as executive controls, and therefore, support the notion that WM is an important function to understand prefrontal functions. On the other hand, although experiments using manual versions of the delayed-response task had revealed many important findings, an oculomotor version of this task enabled us to use multiple cue positions, exclude postural orientation during the delay period, and further prove the importance of mnemonic functions of the prefrontal cortex. In addition, monkeys with unilateral lesions exhibited specific impairment only in the performance of memory-guided saccades directed toward visual cues in the visual field contralateral to the lesioned hemisphere. This result indicates that memories for visuospatial coordinates in each hemifield are processed primarily in the contralateral prefrontal cortex. This result further strengthened the idea of mnemonic functions of the prefrontal cortex. Thus, the mnemonic functions of the prefrontal cortex and delay-period activity may not need to be reconsidered, but should be emphasized. PMID:25698942

  4. Functions of delay-period activity in the prefrontal cortex and mnemonic scotomas revisited.

    PubMed

    Funahashi, Shintaro

    2015-01-01

    Working memory (WM) is one of key concepts to understand functions of the prefrontal cortex. Delay-period activity is an important neural correlate to understand the role of WM in prefrontal functions. The importance of delay-period activity is that this activity can encode not only visuospatial information but also a variety of information including non-spatial visual features, auditory and tactile stimuli, task rules, expected reward, and numerical quantity. This activity also participates in a variety of information processing including sensory-to-motor information transformation. These mnemonic features of delay-period activity enable to perform various important operations that the prefrontal cortex participates in, such as executive controls, and therefore, support the notion that WM is an important function to understand prefrontal functions. On the other hand, although experiments using manual versions of the delayed-response task had revealed many important findings, an oculomotor version of this task enabled us to use multiple cue positions, exclude postural orientation during the delay period, and further prove the importance of mnemonic functions of the prefrontal cortex. In addition, monkeys with unilateral lesions exhibited specific impairment only in the performance of memory-guided saccades directed toward visual cues in the visual field contralateral to the lesioned hemisphere. This result indicates that memories for visuospatial coordinates in each hemifield are processed primarily in the contralateral prefrontal cortex. This result further strengthened the idea of mnemonic functions of the prefrontal cortex. Thus, the mnemonic functions of the prefrontal cortex and delay-period activity may not need to be reconsidered, but should be emphasized.

  5. Network-based inference of protein activity helps functionalize the genetic landscape of cancer

    PubMed Central

    Alvarez, Mariano J.; Shen, Yao; Giorgi, Federico M.; Lachmann, Alexander; Ding, B. Belinda; Ye, B. Hilda; Califano, Andrea

    2016-01-01

    Identifying the multiple dysregulated oncoproteins that contribute to tumorigenesis in a given patient is crucial for developing personalized treatment plans. However, accurate inference of aberrant protein activity in biological samples is still challenging as genetic alterations are only partially predictive and direct measurements of protein activity are generally not feasible. To address this problem we introduce and experimentally validate a new algorithm, VIPER (Virtual Inference of Protein-activity by Enriched Regulon analysis), for the accurate assessment of protein activity from gene expression data. We use VIPER to evaluate the functional relevance of genetic alterations in regulatory proteins across all TCGA samples. In addition to accurately inferring aberrant protein activity induced by established mutations, we also identify a significant fraction of tumors with aberrant activity of druggable oncoproteins—despite a lack of mutations, and vice-versa. In vitro assays confirmed that VIPER-inferred protein activity outperforms mutational analysis in predicting sensitivity to targeted inhibitors. PMID:27322546

  6. Regulation of pumping function of the heart in developing body under changing regimens of motor activity.

    PubMed

    Vafina, E Z; Abzalov, R A; Abzalov, N I; Nikitin, A S; Gulyakov, A A

    2014-06-01

    We analyzed parameters of the pumping function of the heart in rats subjected to enhanced motor activity after a preliminary 70-day hypokinesia under conditions of α- and β-adrenergic receptor stimulation with norepinephrine followed by blockade of β-adrenergic receptor with propranolol (obsidian) and α1-adrenergic receptors with doxazosin. After norepinephrine administration, the HR and cardiac output were higher in rats with enhanced physical activity after preliminary hypokinesia than in rats with low physical activity. After propranolol administration, stroke volume and cardiac output in 100-day-old rats with limited activity were lower, and HR higher was than in rats with enhanced physical activity after preliminary 70-day hypokinesia. After administration of doxazosin, rats with limited motor activity demonstrated more pronounced changes in HR than rats with enhanced physical activity after preliminary 70-day hypokinesia.

  7. ALG-2 activates the MVB sorting function of ALIX through relieving its intramolecular interaction.

    PubMed

    Sun, Sheng; Zhou, Xi; Corvera, Joe; Gallick, Gary E; Lin, Sue-Hwa; Kuang, Jian

    2015-01-01

    The modular adaptor protein ALIX is critically involved in endosomal sorting complexes required for transport (ESCRT)-mediated multivesicular body (MVB) sorting of activated epidermal growth factor receptor (EGFR); however, ALIX contains a default intramolecular interaction that renders ALIX unable to perform this ESCRT function. The ALIX partner protein ALG-2 is a calcium-binding protein that belongs to the calmodulin superfamily. Prompted by a defined biological function of calmodulin, we determined the role of ALG-2 in regulating ALIX involvement in MVB sorting of activated EGFR. Our results show that calcium-dependent ALG-2 interaction with ALIX completely relieves the intramolecular interaction of ALIX and promotes CHMP4-dependent ALIX association with the membrane. EGFR activation induces increased ALG-2 interaction with ALIX, and this increased interaction is responsible for increased ALIX association with the membrane. Functionally, inhibition of ALIX activation by ALG-2 inhibits MVB sorting of activated EGFR as effectively as inhibition of ALIX interaction with CHMP4 does; however, inhibition of ALIX activation by ALG-2 does not affect cytokinetic abscission or equine infectious anemia virus (EIAV) budding. These findings indicate that calcium-dependent ALG-2 interaction with ALIX is specifically responsible for generating functional ALIX that supports MVB sorting of ubiquitinated membrane receptors.

  8. Exploring timing activation of functional pathway based on differential co-expression analysis in preimplantation embryogenesis

    PubMed Central

    Wang, Shanshan; Yang, Lei; Liao, Mingzhi; Wei, Zhuying; Bai, Chunling; Li, Guangpeng

    2016-01-01

    Recent genome-wide omics studies have confirmed the early embryogenesis strictly dependent on the rigorous spatiotemporal activation and multilevel regulation. However, the full effect of functional pathway was not considered. To obtain complete understanding of the gene activation during early development, we performed systematic comparisons based on differential co-expression analysis for bovine preimplantation embryo development (PED). The results confirmed that the functional pathways actively transcribes as early as the 2-cell and 4-cell waves, which Basal transcription factor, Endocytosis and Spliceosome pathway can represent first signs of embryonic activity. Endocytosis act as one of master activators for uncovering a series of successive waves of maternal pioneer signal regulator with the help of Spliceosome complex. Furthermore, the results showed that pattern recognition receptors began to perform its essential function at 4-cell stage, which might be needed to coordinate the later major activation. And finally, our work presented a probable dynamic landscape of key functional pathways for embryogenesis. A clearer understanding of early embryo development will be helpful for Assisted Reproductive Technology (ART) and Regenerative Medicine (RM). PMID:27705919

  9. Paid Work and Physical Activity Preserve Functional Capacity in Elderly People

    PubMed Central

    Ono, Lariane Mortean; Schneider, Ione Jayce Ceola; Confortin, Susana Cararo; d’Orsi, Eleonora

    2015-01-01

    Objective: To investigate the prevalence and association between functional disability and health conditions in elderly people. Method: A cross-sectional, population-based study with 1,705 elderly residents in urban region of Florianópolis, Brazil, from September 2009 to July 2010. The functional disability was classified according to the difficulty in accomplishing six basic activities of daily living. The crude and adjusted multinomial logistic regression was used to identify the associated factors. Results: The prevalence of mild functional disability was 38.9%, and it was positively associated with being female, older age, reporting four or more chronic diseases, overweight, and negative self-perception of health. High education and income, having paid work, and being physically active in leisure activities reduced the chance of presenting it. The prevalence of moderate/severe disability was 11.7% and positively associated with older age, presence of depressive symptoms, four or more chronic diseases, and negative self-perception of health. High education, paid work, and being physically active in leisure activities also reduced the chance of presenting moderate/severe disability. Conclusion: Being gainfully employed, having a high level of education, and being physically active in their leisure time reduced the chance of presenting disability. The negative self-perception of health was the factor that most increased the chance of presenting functional disability. PMID:28138470

  10. Pain mediates the association between physical activity and the impact of fibromyalgia on daily function.

    PubMed

    Umeda, Masataka; Corbin, Lisa W; Maluf, Katrina S

    2015-01-01

    This study quantified the association between recreational physical activity and daily function in women with fibromyalgia, and determined if this association is mediated by symptoms of pain, depression, or body mass. Twenty-three women diagnosed with fibromyalgia participated in an observational survey study. Recreational physical activity and the impact of fibromyalgia on daily function were assessed using the sport and leisure time physical activity subscales of the Baecke Physical Activity Questionnaire (BPAQ) and the Fibromyalgia Impact Questionnaire (FIQ), respectively. Potential mediators of the association between physical activity and daily function were assessed using the Visual Analogue Scale for pain intensity (VAS-Pain), the Beck Depression Inventory (BDI), and body mass index (BMI). BPAQ was inversely associated with FIQ (R (2) = 0.20) and VAS-Pain (R (2) = 0.39). VAS-Pain was positively associated with FIQ (R (2) = 0.23). The inverse association between BPAQ and FIQ was no longer significant after controlling for VAS-Pain. BDI was positively associated with FIQ (R (2) = 0.37), whereas BMI was not. BPAQ was not significantly associated with either BDI or BMI. These results indicate that the intensity of musculoskeletal pain, rather than depressive symptoms or body mass, mediates the association between physical activity and daily function among women with fibromyalgia.

  11. Systemic endothelial function is preserved in men with both active and inactive variant angina pectoris.

    PubMed

    Ito, K; Akita, H; Kanazawa, K; Yamada, S; Shiga, N; Terashima, M; Matsuda, Y; Takai, E; Iwai, C; Takaoka, H; Yokoyama, M

    1999-12-01

    To test the hypothesis that coronary spasm could be a coronary manifestation of systemic endothelial dysfunction and that the activity of coronary spasm could influence systemic endothelial function, we examined brachial flow-mediated, endothelium-dependent vasodilation and nitroglycerin-induced endothelium-independent vasodilation with high-resolution ultrasound in 11 men with variant angina pectoris (6 active and 5 inactive) without established coronary atherosclerosis. Endothelium-dependent vasodilation in peripheral circulation was preserved in men with active and inactive variant angina pectoris, suggesting that systemic endothelial dysfunction is not involved in either the pathogenesis or the activity of coronary spasm.

  12. Intrinsic muscle strength and voluntary activation of both lower limbs and functional performance after stroke.

    PubMed

    Horstman, Astrid M; Beltman, Marijke J; Gerrits, Karin H; Koppe, Peter; Janssen, Thomas W; Elich, Peter; de Haan, Arnold

    2008-07-01

    The objective of this study was to assess the nature of muscle weakness in both legs after stroke compared with able-bodied control individuals and to examine whether there is a relationship between the degree of muscle weakness and coactivation of knee extensors and flexors as well as voluntary activation capacity of knee extensors of both paretic and non-paretic legs and indices of functional performance. Maximal voluntary isometric torques of knee extensors (MVCe) and flexors (MVCf) were determined in 14 patients (bilaterally) and 12 able-bodied controls. Simultaneous measurements were made of torque and surface EMG from agonist and antagonist muscles. Coactivation was calculated. Supramaximal triplets were evoked with electrical stimulation to estimate maximal torque capacity and degree of voluntary activation of knee extensors. MVCs, activation and coactivation parameters were correlated to scores of seven functional performance tests. MVCe, MVCf and voluntary activation were lower in paretic lower limb (PL) compared with both non-paretic lower limb (NL) and control. Besides, all these parameters of NL were also lower than control. Electrically evoked torque capacity of knee extensors of PL was about 60% of both NL and control, which were not significantly different from each other. Strong significant correlations between strength, as well as voluntary activation, and functional performance were found. Coactivation did not correlate well with functional performance. Thus, whereas for NL activation failure can explain weakness, for PL both activation failure and reduced intrinsic torque capacity are responsible for the severe weakness. Activation capacity and muscle strength correlated strongly to functional performance, while coactivation did not.

  13. Premature Sperm Activation and Defective Spermatogenesis Caused by Loss of spe-46 Function in Caenorhabditis elegans

    PubMed Central

    Liau, Wei-Siang; Nasri, Ubaydah; Elmatari, Daniel; Rothman, Jason; LaMunyon, Craig W.

    2013-01-01

    Given limited resources for motility, sperm cell activation must be precisely timed to ensure the greatest likelihood of fertilization. Like those of most species, the sperm of C. elegans become active only after encountering an external signaling molecule. Activation coincides with spermiogenesis, the final step in spermatogenesis, when the spherical spermatid undergoes wholesale reorganization to produce a pseudopod. Here, we describe a gene involved in sperm activation, spe-46. This gene was identified in a suppressor screen of spe-27(it132ts), a sperm-expressed gene whose product functions in the transduction of the spermatid activation signal. While spe-27(it132ts) worms are sterile at 25°C, the spe-46(hc197)I; spe-27(it132ts)IV double mutants regain partial fertility. Single nucleotide polymorphism mapping, whole genome sequencing, and transformation rescue were employed to identify the spe-46 coding sequence. It encodes a protein with seven predicted transmembrane domains but with no other predicted functional domains or homology outside of nematodes. Expression is limited to spermatogenic tissue, and a transcriptional GFP fusion shows expression corresponds with the onset of the pachytene stage of meiosis. The spe-46(hc197) mutation bypasses the need for the activation signal; mutant sperm activate prematurely without an activation signal in males, and mutant males are sterile. In an otherwise wild-type genome, the spe-46(hc197) mutation induces a sperm defective phenotype. In addition to premature activation, spe-46(hc197) sperm exhibit numerous defects including aneuploidy, vacuolization, protruding spikes, and precocious fusion of membranous organelles. Hemizygous worms [spe-46(hc197)/mnDf111] are effectively sterile. Thus, spe-46 appears to be involved in the regulation of spermatid activation during spermiogenesis, with the null phenotype being an absence of functional sperm and hypomorphic phenotypes being premature spermatid activation and numerous

  14. The effect of Jewish religiosity of elderly Israelis on their life satisfaction, health, function and activity.

    PubMed

    Shkolnik, T; Weiner, C; Malik, L; Festinger, Y

    2001-01-01

    The purpose of this study was to examine the factors that make for 'successful aging'. In particular, we examined the relationship between the degree of religious or traditional observance on overall life satisfaction, health, function, and activity of an elderly population. The subjects chosen were aged from 68 to 75 and were divided into two groups: 37 percent were traditionally observant ('traditional') and 67 percent religiously observant ('religious'). Overall the sociodemographic features of both groups were similar. The results of the study did show, however, that the most significant factors in influencing the subjects' life satisfaction were religiosity and functional adequacy. Our conclusions from these findings indicate that the religious observant elderly person, who is religiously active, retains a social status that earns him respect because of this activity. This status even provides him with a source of power in his social group, as a result of which he functions more effectively and is more satisfied with life.

  15. An investigation of the relationship between activation of a social cognitive neural network and social functioning.

    PubMed

    Pinkham, Amy E; Hopfinger, Joseph B; Ruparel, Kosha; Penn, David L

    2008-07-01

    Previous work examining the neurobiological substrates of social cognition in healthy individuals has reported modulation of a social cognitive network such that increased activation of the amygdala, fusiform gyrus, and superior temporal sulcus are evident when individuals judge a face to be untrustworthy as compared with trustworthy. We examined whether this pattern would be present in individuals with schizophrenia who are known to show reduced activation within these same neural regions when processing faces. Additionally, we sought to determine how modulation of this social cognitive network may relate to social functioning. Neural activation was measured using functional magnetic resonance imaging with blood oxygenation level dependent contrast in 3 groups of individuals--nonparanoid individuals with schizophrenia, paranoid individuals with schizophrenia, and healthy controls--while they rated faces as either trustworthy or untrustworthy. Analyses of mean percent signal change extracted from a priori regions of interest demonstrated that both controls and nonparanoid individuals with schizophrenia showed greater activation of this social cognitive network when they rated a face as untrustworthy relative to trustworthy. In contrast, paranoid individuals did not show a significant difference in levels of activation based on how they rated faces. Further, greater activation of this social cognitive network to untrustworthy faces was significantly and positively correlated with social functioning. These findings indicate that impaired modulation of neural activity while processing social stimuli may underlie deficits in social cognition and social dysfunction in schizophrenia.

  16. Self-reported Physical Activity Predicts Pain Inhibitory and Facilitatory Function

    PubMed Central

    Naugle, Kelly M.; Riley, Joseph L.

    2013-01-01

    Considerable evidence suggests regular physical activity can reduce chronic pain symptoms. Dysfunction of endogenous facilitatory and inhibitory systems has been implicated in multiple chronic pain conditions. However, few studies have investigated the relationship between levels of physical activity and descending pain modulatory function. Purpose This study’s purpose was to determine whether self-reported levels of physical activity in healthy adults predicted 1) pain sensitivity to heat and cold stimuli, 2) pain facilitatory function as tested by temporal summation of pain (TS), and 3) pain inhibitory function as tested by conditioned pain modulation (CPM) and offset analgesia. Methods Forty-eight healthy adults (age range 18–76) completed the International Physical Activity Questionnaire (IPAQ) and the following pain tests: heat pain thresholds (HPT), heat pain suprathresholds, cold pressor pain (CPP), temporal summation of heat pain, conditioned pain modulation, and offset analgesia. The IPAQ measured levels of walking, moderate, vigorous and total physical activity over the past seven days. Hierarchical linear regressions were conducted to determine the relationship between each pain test and self-reported levels of physical activity, while controlling for age, sex and psychological variables. Results Self-reported total and vigorous physical activity predicted TS and CPM (p’s <.05). Individuals who self-reported more vigorous and total physical activity exhibited reduced temporal summation of pain and greater CPM. The IPAQ measures did not predict any of the other pain measures. Conclusion Thus, these results suggest that healthy older and younger adults who self-report greater levels of vigorous and total physical activity exhibit enhanced descending pain modulatory function. Improved descending pain modulation may be a mechanism through which exercise reduces or prevents chronic pain symptoms. PMID:23899890

  17. An Active Lifestyle is Associated with Better Neurocognitive Functioning in Adults Living with HIV-infection

    PubMed Central

    Fazeli, Pariya L.; Woods, Steven Paul; Heaton, Robert K.; Umlauf, Anya; Gouaux, Ben; Rosario, Debra; Moore, Raeanne C.; Grant, Igor; Moore, David J.

    2014-01-01

    Studies of healthy adults show that engagement in physical, social, and mental activities is associated with better cognitive outcomes, suggesting these activities may increase cognitive reserve. Given the prevalence and real-world impact of HIV-associated neurocognitive disorders (HAND), the present study examined the association between neurocognitive outcomes and self-reported proxies for physical exercise, social activity, and mental activity (employment was used as a proxy for mental activity) among 139 HIV-infected adults (Mage = 48.7; 48% age 50+). Participants completed a neuromedical and neuropsychological battery and were classified based on the number of self-reported active lifestyle factors (ALFs; 0 to 3), including physical exercise, social activity, and current employment. The association between ALFs and both demographically-adjusted average neuropsychological T-scores and HAND diagnoses were examined. Results revealed that an increased number of ALFs was associated with better global neurocognitive performance as well as a lower prevalence of HAND. These cross-sectional findings suggest that an active engagement in life may bolster neurocognitive functioning, perhaps by enhancing cognitive and/or brain reserve. However, an alternative explanation might be that persons with better neurocognitive functioning are more inclined and able to engage in these life activities. Future studies should utilize neuroimaging methodology, longitudinal data, and interventional approaches to establish cause-effect relationships and uncover the neural mechanisms whereby physical, social, and mental stimulation may protect neurocognition via cognitive reserve among those living with HIV. PMID:24554483

  18. PREX1 Protein Function Is Negatively Regulated Downstream of Receptor Tyrosine Kinase Activation by p21-activated Kinases (PAKs).

    PubMed

    Barrows, Douglas; He, John Z; Parsons, Ramon

    2016-09-16

    Downstream of receptor tyrosine kinase and G protein-coupled receptor (GPCR) stimulation, the phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent Rac exchange factor (PREX) family of guanine nucleotide exchange factors (GEFs) activates Rho GTPases, leading to important roles for PREX proteins in numerous cellular processes and diseases, including cancer. PREX1 and PREX2 GEF activity is activated by the second messengers PIP3 and Gβγ, and further regulation of PREX GEF activity occurs by phosphorylation. Stimulation of receptor tyrosine kinases by neuregulin and insulin-like growth factor 1 (IGF1) leads to the phosphorylation of PREX1; however, the kinases that phosphorylate PREX1 downstream of these ligands are not known. We recently reported that the p21-activated kinases (PAKs), which are activated by GTP-bound Ras-related C3 botulinum toxin substrate 1 (Rac1), mediate the phosphorylation of PREX2 after insulin receptor activation. Here we show that certain phosphorylation events on PREX1 after insulin, neuregulin, and IGF1 treatment are PAK-dependent and lead to a reduction in PREX1 binding to PIP3 Like PREX2, PAK-mediated phosphorylation also negatively regulates PREX1 GEF activity. Furthermore, the onset of PREX1 phosphorylation was delayed compared with the phosphorylation of AKT, supporting a model of negative feedback downstream of PREX1 activation. We also found that the phosphorylation of PREX1 after isoproterenol and prostaglandin E2-mediated GPCR activation is partially PAK-dependent and likely also involves protein kinase A, which is known to reduce PREX1 function. Our data point to multiple mechanisms of PREX1 negative regulation by PAKs within receptor tyrosine kinase and GPCR-stimulated signaling pathways that have important roles in diseases such as diabetes and cancer.

  19. Beyond apoptosis: the mechanism and function of phosphatidylserine asymmetry in the membrane of activating mast cells.

    PubMed

    Rysavy, Noel M; Shimoda, Lori M N; Dixon, Alyssa M; Speck, Mark; Stokes, Alexander J; Turner, Helen; Umemoto, Eric Y

    2014-01-01

    Loss of plasma membrane asymmetry is a hallmark of apoptosis, but lipid bilayer asymmetry and loss of asymmetry can contribute to numerous cellular functions and responses that are independent of programmed cell death. Exofacial exposure of phosphatidylserine occurs in lymphocytes and mast cells after antigenic stimulation and in the absence of apoptosis, suggesting that there is a functional requirement for phosphatidylserine exposure in immunocytes. In this review we examine current ideas as to the nature of this functional role in mast cell activation. Mechanistically, there is controversy as to the candidate proteins responsible for phosphatidylserine translocation from the internal to external leaflet, and here we review the candidacies of mast cell PLSCR1 and TMEM16F. Finally we examine the potential relationship between functionally important mast cell membrane perturbations and phosphatidylserine exposure during activation.

  20. Beyond apoptosis: The mechanism and function of phosphatidylserine asymmetry in the membrane of activating mast cells

    PubMed Central

    Rysavy, Noel M.; Shimoda, Lori M. N.; Dixon, Alyssa M.; Speck, Mark; Stokes, Alexander J.; Turner, Helen; Umemoto, Eric Y.

    2014-01-01

    Loss of plasma membrane asymmetry is a hallmark of apoptosis, but lipid bilayer asymmetry and loss of asymmetry can contribute to numerous cellular functions and responses that are independent of programmed cell death. Exofacial exposure of phosphatidylserine occurs in lymphocytes and mast cells after antigenic stimulation and in the absence of apoptosis, suggesting that there is a functional requirement for phosphatidylserine exposure in immunocytes. In this review we examine current ideas as to the nature of this functional role in mast cell activation. Mechanistically, there is controversy as to the candidate proteins responsible for phosphatidylserine translocation from the internal to external leaflet, and here we review the candidacies of mast cell PLSCR1 and TMEM16F. Finally we examine the potential relationship between functionally important mast cell membrane perturbations and phosphatidylserine exposure during activation. PMID:25759911

  1. Task-modulated activation and functional connectivity of the temporal and frontal areas during speech comprehension.

    PubMed

    Yue, Q; Zhang, L; Xu, G; Shu, H; Li, P

    2013-05-01

    There is general consensus in the literature that a distributed network of temporal and frontal brain areas is involved in speech comprehension. However, how active versus passive tasks modulate the activation and the functional connectivity of the critical brain areas is not clearly understood. In this study, we used functional magnetic resonance imaging (fMRI) to identify intelligibility and task-related effects in speech comprehension. Participants performed a semantic judgment task on normal and time-reversed sentences, or passively listened to the sentences without making an overt response. The subtraction analysis demonstrated that passive sentence comprehension mainly engaged brain areas in the left anterior and posterior superior temporal sulcus and middle temporal gyrus (aSTS/MTG and pSTS/MTG), whereas active sentence comprehension recruited bilateral frontal regions in addition to the aSTS/MTG and pSTS/MTG regions. Functional connectivity analysis revealed that during passive sentence comprehension, the left aSTS/MTG was functionally connected with the left Heschl's gyrus (HG) and bilateral superior temporal gyrus (STG) but no area was functionally connected with the left pSTS/MTG; during active sentence comprehension, however, both the left aSTS/MTG and pSTS/MTG were functionally connected with bilateral superior temporal and inferior frontal areas. While these results are consistent with the view that the ventral stream of the temporo-frontal network subserves semantic processing, our findings further indicate that both the activation and the functional connectivity of the temporal and frontal areas are modulated by task demands.

  2. Modulating NMDA Receptor Function with D-Amino Acid Oxidase Inhibitors: Understanding Functional Activity in PCP-Treated Mouse Model

    PubMed Central

    Sershen, Henry; Hashim, Audrey; Dunlop, David S.; Suckow, Raymond F.; Cooper, Tom B.; Javitt, Daniel C.

    2016-01-01

    Deficits in N-methyl-D-aspartate receptor (NMDAR) function are increasingly linked to persistent negative symptoms and cognitive deficits in schizophrenia. Accordingly, clinical studies have been targeting the modulatory site of the NMDA receptor, based on the decreased function of NMDA receptor, to see whether increasing NMDA function can potentially help treat the negative and cognitive deficits seen in the disease. Glycine and D-serine are endogenous ligands to the NMDA modulatory site, but since high doses are needed to affect brain levels, related compounds are being developed, for example glycine transport (GlyT) inhibitors to potentially elevate brain glycine or targeting enzymes, such as D-amino acid oxidase (DAAO) to slow the breakdown and increase the brain level of D-serine. In the present study we further evaluated the effect of DAAO inhibitors 5-chloro-benzo[d]isoxazol-3-ol (CBIO) and sodium benzoate (NaB) in a phencyclidine (PCP) rodent mouse model to see if the inhibitors affect PCP-induced locomotor activity, alter brain D-serine level, and thereby potentially enhance D-serine responses. D-Serine dose-dependently reduced the PCP-induced locomotor activity at doses above 1000 mg/kg. Acute CBIO (30 mg/kg) did not affect PCP-induced locomotor activity, but appeared to reduce locomotor activity when given with D-serine (600 mg/kg); a dose that by itself did not have an effect. However, the effect was also present when the vehicle (Trappsol®) was tested with D-serine, suggesting that the reduction in locomotor activity was not related to DAAO inhibition, but possibly reflected enhanced bioavailability of D-serine across the blood brain barrier related to the vehicle. With this acute dose of CBIO, D-serine level in brain and plasma were not increased. Another weaker DAAO inhibitor sodium benzoate (NaB) (400 mg/kg), and NaB plus D-serine also significantly reduced PCP-induced locomotor activity, but without affecting plasma or brain D-serine level

  3. Platelet factor 4 stimulates thrombomodulin protein C-activating cofactor activity. A structure-function analysis.

    PubMed

    Slungaard, A; Key, N S

    1994-10-14

    Thrombomodulin (TM) is an anionic (pI approximately 4) protein cofactor that promotes thrombin (THR) cleavage of protein C to generate activated protein C (APC), a potent anticoagulant. We find that the cationic platelet alpha-granule protein platelet factor 4 (PF4) stimulates 4-25-fold the cofactor activity of rabbit TM and two differentially glycanated versions of an extracellular domain human TM polypeptide in which the glycosaminoglycan (GAG) is either present (GAG+ TM) or absent (GAG- TM) with an ED50 of 3.3-10 micrograms/ml. No such stimulation occurs in response to beta-thromboglobulin or thrombospondin, or when protein C lacking its gamma-carboxyglutamic acid (Gla) domain is the substrate. Heparin and chondroitin sulfates A and E reverse PF4 stimulation. PF4 minimally affects the Kd for THR but decreases 30-fold (from 8.3 to 0.3 microM) the Km for protein C of APC generation by GAG+ TM. PF4 also strikingly transforms the [Ca2+] dependence profile of rabbit and GAG+ TM to resemble that of GAG- TM. A potential explanation for this is that PF4, like Ca2+, induces heparin-reversible alterations in native (but not Gla-domainless) protein C conformation as assessed by autofluorescence emission analysis. We conclude that PF4 stimulates TM APC generation by interacting electrostatically with both the TM GAG and the protein C Gla domain to enhance markedly the affinity of the THR.TM complex for protein C. By this mechanism, PF4 may play a previously unsuspected role in the physiologic regulation of clotting.

  4. Depth-resolved imaging of functional activation in the rat cerebral cortex using optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Aguirre, A. D.; Chen, Y.; Fujimoto, J. G.; Ruvinskaya, L.; Devor, A.; Boas, D. A.

    2006-12-01

    Co-registered optical coherence tomography (OCT) and video microscopy of the rat somatosensory cortex were acquired simultaneously through a thinned skull during forepaw electrical stimulation. Fractional signal change measured by OCT revealed a functional signal time course corresponding to the hemodynamic signal measurement made with video microscopy. OCT can provide high-resolution, cross-sectional images of functional neurovascular activation and may offer a new tool for basic neuroscience research in the important rat cerebral cortex model.

  5. Global asymptotical stability of continuous-time delayed neural networks without global Lipschitz activation functions

    NASA Astrophysics Data System (ADS)

    Tan, Yong; Tan, Mingjia

    2009-11-01

    This paper investigates the global asymptotic stability of equilibrium for a class of continuous-time neural networks with delays. Based on suitable Lyapunov functionals and the homeomorphism theory, some sufficient conditions for the existence and uniqueness of the equilibrium point are derived. These results extend the previously works without assuming boundedness and Lipschitz conditions of the activation functions and any symmetry of interconnections. A numerical example is also given to show the improvements of the paper.

  6. Development of Activity-based Cost Functions for Cellulase, Invertase, and Other Enzymes

    NASA Astrophysics Data System (ADS)

    Stowers, Chris C.; Ferguson, Elizabeth M.; Tanner, Robert D.

    As enzyme chemistry plays an increasingly important role in the chemical industry, cost analysis of these enzymes becomes a necessity. In this paper, we examine the aspects that affect the cost of enzymes based upon enzyme activity. The basis for this study stems from a previously developed objective function that quantifies the tradeoffs in enzyme purification via the foam fractionation process (Cherry et al., Braz J Chem Eng 17:233-238, 2000). A generalized cost function is developed from our results that could be used to aid in both industrial and lab scale chemical processing. The generalized cost function shows several nonobvious results that could lead to significant savings. Additionally, the parameters involved in the operation and scaling up of enzyme processing could be optimized to minimize costs. We show that there are typically three regimes in the enzyme cost analysis function: the low activity prelinear region, the moderate activity linear region, and high activity power-law region. The overall form of the cost analysis function appears to robustly fit the power law form.

  7. Functional Improvement Following Diastasis Rectus Abdominus Repair in an Active Duty Navy Female.

    PubMed

    Gallus, Katerina M; Golberg, Kathy F; Field, Robert

    2016-08-01

    Return to physical activity following childbirth can be a difficult process complicated by structural changes during pregnancy. A common problem is the development of a diastasis of the rectus abdominus (DRA), defined as a horizontal separation of the abdominus muscles at the linea alba. Recent data indicate that the greater the distance of separation of the muscle, the worse the functional ability. We describe a 24-year-old active duty U.S. Navy female G1P2 with a diagnosis of DRA. At 2 months postpartum, she was referred to physical therapy because of back pain and inability to meet baseline activities of daily living. After 4 months of physical therapy, she was unable to complete curl ups as required by U.S. Navy physical fitness standards. Abdominoplasty with imbrication of the abdominal wall diastasis was performed followed by additional physical therapy, after which she returned to baseline functioning. The restoration of functional ability postoperatively suggests there is a therapeutic indication for surgical correction of DRA. In high-functioning military patients with DRA who fail to return to baseline level of activity following a trial of physical therapy, surgical intervention should be considered to obtain the optimal functional ability.

  8. The fast neutron fluence and the activation detector activity calculations using the effective source method and the adjoint function

    SciTech Connect

    Hep, J.; Konecna, A.; Krysl, V.; Smutny, V.

    2011-07-01

    This paper describes the application of effective source in forward calculations and the adjoint method to the solution of fast neutron fluence and activation detector activities in the reactor pressure vessel (RPV) and RPV cavity of a VVER-440 reactor. Its objective is the demonstration of both methods on a practical task. The effective source method applies the Boltzmann transport operator to time integrated source data in order to obtain neutron fluence and detector activities. By weighting the source data by time dependent decay of the detector activity, the result of the calculation is the detector activity. Alternatively, if the weighting is uniform with respect to time, the result is the fluence. The approach works because of the inherent linearity of radiation transport in non-multiplying time-invariant media. Integrated in this way, the source data are referred to as the effective source. The effective source in the forward calculations method thereby enables the analyst to replace numerous intensive transport calculations with a single transport calculation in which the time dependence and magnitude of the source are correctly represented. In this work, the effective source method has been expanded slightly in the following way: neutron source data were performed with few group method calculation using the active core calculation code MOBY-DICK. The follow-up neutron transport calculation was performed using the neutron transport code TORT to perform multigroup calculations. For comparison, an alternative method of calculation has been used based upon adjoint functions of the Boltzmann transport equation. Calculation of the three-dimensional (3-D) adjoint function for each required computational outcome has been obtained using the deterministic code TORT and the cross section library BGL440. Adjoint functions appropriate to the required fast neutron flux density and neutron reaction rates have been calculated for several significant points within the RPV

  9. Thyroid function in fasting rats: variations in 131I uptake and transient decrease in peroxidase activity.

    PubMed

    Moura, E G; Ramos, C F; Nascimento, C C; Rosenthal, D; Breitenbach, M M

    1987-01-01

    Serum thyroxine and triiodothyronine, radioiodide thyroid uptake and thyroid peroxidase (TPO) activity were studied over a 2 to 5 day period in fasting rats treated (F+) or not (F-) with TSH. In F- rats, TPO activity was transiently decreased on the 3rd day, whereas in F+ it was always higher than in controls. On the 5th day, the 2 h thyroid uptake of 131I decreased in F-, while the 24 h uptake increased in both F- and F+. Serum T3 and T4 decreased in both fasting groups. Thus, not all effects of fasting on rat thyroid function are reverted by TSH administration, suggesting intrinsic impairment of glandular function.

  10. Lag Synchronization of Switched Neural Networks via Neural Activation Function and Applications in Image Encryption.

    PubMed

    Wen, Shiping; Zeng, Zhigang; Huang, Tingwen; Meng, Qinggang; Yao, Wei

    2015-07-01

    This paper investigates the problem of global exponential lag synchronization of a class of switched neural networks with time-varying delays via neural activation function and applications in image encryption. The controller is dependent on the output of the system in the case of packed circuits, since it is hard to measure the inner state of the circuits. Thus, it is critical to design the controller based on the neuron activation function. Comparing the results, in this paper, with the existing ones shows that we improve and generalize the results derived in the previous literature. Several examples are also given to illustrate the effectiveness and potential applications in image encryption.

  11. EGF Regulation of Nuclear Co-Activator AIB1 Function in Breast Cancer

    DTIC Science & Technology

    2005-04-01

    AD Award Number: DAMDl7-02-1-0394 TITLE: EGF Regulation of Nuclear Co-Activator AIBI Function in Breast Cancer PRINCIPAL INVESTIGATOR: Annabell S. Oh...Activator AIBI Function in DAMD17-02-1-0394 Breast Cancer 6. AUTHOR(S) Annabell S. Oh 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING...Factor-i Signaling in Human Breast Cancer. Doctoral dissertation of Annabell S. Oh, B.S. from the Department 14 of Tumor Biology, Georgetown

  12. Functional biomimetic models for the active site in the respiratory enzyme cytochrome c oxidase.

    PubMed

    Collman, James P; Decréau, Richard A

    2008-11-07

    A functional analog of the active site in the respiratory enzyme, cytochrome c oxidase (CcO) reproduces every feature in CcO's active site: a myoglobin-like heme (heme a3), a distal tridentate imidazole copper complex (Cu(B)), a phenol (Tyr244), and a proximal imidazole. When covalently attached to a liquid-crystalline SAM film on an Au electrode, this functional model continuously catalyzes the selective four-electron reduction of dioxygen at physiological potential and pH, under rate-limiting electron flux (as occurs in CcO).

  13. Light-Intensity Activity Attenuates Functional Decline in Older Cancer Survivors

    PubMed Central

    Blair, Cindy K.; Morey, Miriam C.; Desmond, Renee A.; Cohen, Harvey Jay; Sloane, Richard; Snyder, Denise C.; Demark-Wahnefried, Wendy

    2014-01-01

    While moderate-vigorous intensity physical activities (MVPA) confer the greatest health benefits, evidence suggests that light-intensity activities are also beneficial, particularly for older adults and individuals with moderate-severe comorbidities. Purpose To examine cross-sectional and longitudinal associations between light-intensity activity and physical function in older cancer survivors at increased risk for age- and treatment-related comorbidities, including accelerated functional decline. Methods The analysis included data from 641 breast, prostate, and colorectal cancer survivors (54% female) aged 65 and older who participated in a 1-year, home-based diet and exercise intervention designed to reduce the rate of physical function decline. ANCOVA was used to compare means of physical function across levels of PA intensity (low-light (LLPA): 1.5-2.0 METs; high-light (HLPA): 2.1-2.9 METs; MVPA: ≥3.0 METs). Results In cross-sectional analyses, increasing tertiles of light-intensity activity were associated with higher scores for all 3 measures of physical function (all p-values <0.005), after adjustment for age, sex, BMI, comorbidity, symptoms, and MVPA. Associations were stronger for HLPA than for LLPA. Compared with survivors who decreased or remained stable in MVPA and HLPA at the post-intervention follow-up, those who increased in HLPA, but decreased or remained stable in MVPA, reported higher physical function scores (LSMeans (95% CI): SF-36 physical function subscale: -5.58 (-7.96, -3.20) vs. -2.54 (-5.83, 0.75), p=0.14; basic lower extremity function: -2.00 (-3.45, -0.55) vs. 0.28 (-1.72, 2.28), p=0.07; advanced lower extremity function: -2.58 (-4.00, -1.15) vs. 0.44 (-1.52, 2.40), p=0.01). Conclusion Our findings suggest that increasing light-intensity activities, especially HLPA, may be a viable approach to reducing the rate of physical function decline in individuals who are unable or reluctant to initiate or maintain adequate levels of moderate

  14. Abnormal cortical functional activity in patients with ischemic white matter lesions: A resting-state functional magnetic resonance imaging study.

    PubMed

    Ding, Xin; Ding, Jurong; Hua, Bo; Xiong, Xingzhong; Xiao, Li; Peng, Fang; Chen, Lin; Pan, Xianfang; Wang, Qingsong

    2017-02-09

    There is increasing evidence that white matter lesions (WMLs) are associated with cognitive impairments. The purpose of this study was to explore the relationship of WMLs with cognitive impairments from the aspect of cortical functional activity. Briefly, Sixteen patients with ischemic WMLs and 13 controls participated in this study. A regional homogeneity (ReHo) approach was used to investigate altered neural coherence in patients with ischemic WMLs during the resting state. A correlation analysis was further performed between regions with altered ReHo and cognitive test scores, including Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), in the patient group. Finally, we found regions with altered ReHo values in patients with ischemic WMLs to be involved in default mode network (DMN), frontal-parietal control network (FPCN), dorsal attention network (DAN), motor network and right temporal cortex. Moreover, some altered regions belonging to DMN, FPCN and motor network were significantly correlated with cognitive test scores. Our results provide neuroimaging evidence for the impairments of memory, attention, executive and motor function in patients with ischemic WMLs. It is interesting to note that the decreased ReHo was mainly in the anterior brain regions, while increased ReHo in the posterior brain regions, which may indicate a failure down regulation of spontaneous activity in posterior regions. In summary, this study indicates an important role of specific cortical dysfunction in cognitive associated with WMLs.

  15. Bioactive Components and Functional Properties of Biologically Activated Cereal Grains: A Bibliographic Review.

    PubMed

    Singh, Arashdeep; Sharma, Savita

    2015-10-14

    Whole grains provide energy, nutrients, fibres and bioactive compounds that may synergistically contribute to their protective effects. A wide range of these compounds is affected by germination. While some compounds, such as β-glucans are degraded, others, like antioxidants and total phenolics are increased by means of biological activation of grains. The water and oil absorption capacity as well as emulsion and foaming capacity of biologically activated grains are also improved. Application of biological activation of grains is of emerging interest, which may significantly enhance the nutritional, functional and bioactive content of grains, as well as improve palatability of grain foods in a natural way. Therefore, biological activation of cereals can be a way to produce food grains enriched with health promoting compounds and enhanced functional attributes.

  16. Sexual function in Moroccan women with rheumatoid arthritis and its relationship with disease activity.

    PubMed

    Hari, Asmae; Rostom, Samira; Lahlou, Racha; Bahiri, Rachid; Hajjaj-Hassouni, Najia

    2015-06-01

    The objective of this study was to evaluate sexual function in women with rheumatoid arthritis (RA) using an auto-questionnaire Female Sexual Function Index (FSFI) and study its correlation with disease activity. Sixty patients with RA and 40 healthy controls were included in this exploratory study. Sociodemographic, clinical, and laboratory characteristics were assessed. The disease activity was assessed by auto-questionnaires Routine Assessment of Patient Index Data 3 (RAPID3) and Rheumatoid Arthritis Disease Activity Index 5 (RADAI5) judged by 28 DAS ESR. Sexual function was assessed by an auto-questionnaire specific for female sexuality: FSFI during the last 4 weeks. The definition of sexual dysfunction was considered by FSFI score less than or equal to 26.5. The mean age of RA patients and controls was 45.95 ± 9.3 and 45.01 ± 9.2, respectively. According to FSFI, the percentage of FSD in women with RA was significantly higher than that in the control group. All dimensions of sexuality were affected (desire, arousal, lubrication, orgasm, and satisfaction) except pain. The multivariate linear regression analysis indicated that the swollen joints and the RADAI5 were the independent variables of disease activity associated with sexual dysfunction in women with RA. This study suggests that sexual dysfunction among women suffering from rheumatoid arthritis is found when a targeted questionnaire is used to identify it and that the increased disease activity has a negative effect of sexual function.

  17. The relation of hand functions with radiological damage and disease activity in rheumatoid arthritis.

    PubMed

    Birtane, Murat; Kabayel, Derya Demirbag; Uzunca, Kaan; Unlu, Ercument; Tastekin, Nurettin

    2008-03-01

    The purpose of this study was to investigate specifically the correlation of hand functions determined by Duruoz hand index (DHI) with radiological findings and disease activity in rheumatoid arthritis (RA) patients. Forty-eight RA patients were evaluated with DHI questionnaire, disease activity score (DAS) 28 and modified Larsen scoring method. Correlation between DAS-28 and DHI was assessed in all the patients. Mean DHI scores were compared between patients in remission (DAS-28 < 2.6) and patients who have more or less disease activity (DAS-28 >or= 2.6). To exclude the probable conflicting effect of disease activity on hand functions, the correlation between radiological scores and DHI was investigated only in patients with remission. There was a positive correlation between DAS-28 and DHI in all patients group (r = 0.434, P < 0.002). No correlation between the radiological scores of any joint groups and DHI could be found in patients with remission. Hand functions seemed to be affected prominently from disease activity. Radiological scores demonstrating joint damage were not in relation with hand functions.

  18. An investigation into the relationship between age and physiological function in highly active older adults

    PubMed Central

    Pollock, Ross D; Carter, Scott; Velloso, Cristiana P; Duggal, Niharika A; Lord, Janet M; Lazarus, Norman R; Harridge, Stephen D R

    2015-01-01

    Despite extensive research, the relationship between age and physiological function remains poorly characterised and there are currently no reliable markers of human ageing. This is probably due to a number of confounding factors, particularly in studies of a cross-sectional nature. These include inter-subject genetic variation, as well as inter-generational differences in nutrition, healthcare and insufficient levels of physical activity as well as other environmental factors. We have studied a cohort of highly and homogeneously active older male (n = 84) and female (n = 41) cyclists aged 55–79 years who it is proposed represent a model for the study of human ageing free from the majority of confounding factors, especially inactivity. The aim of the study was to identify physiological markers of ageing by assessing the relationship between function and age across a wide range of indices. Each participant underwent a detailed physiological profiling which included measures of cardiovascular, respiratory, neuromuscular, metabolic, endocrine and cognitive functions, bone strength, and health and well-being. Significant associations between age and function were observed for many functions. The maximal rate of oxygen consumption ( showed the closest association with age (r = −0.443 to −0.664; P < 0.001), but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The results of this cross-sectional study suggest that even when many confounding variables are removed the relationship between function and healthy ageing is complex and likely to be highly individualistic and that physical activity levels must be taken into account in ageing studies. Key Points The relationship between age and physiological function remains poorly defined and there are no physiological markers that can be used to reliably predict the age of an individual. This could be due to a variety of confounding

  19. A FRET biosensor reveals spatiotemporal activation and functions of aurora kinase A in living cells.

    PubMed

    Bertolin, Giulia; Sizaire, Florian; Herbomel, Gaëtan; Reboutier, David; Prigent, Claude; Tramier, Marc

    2016-09-14

    Overexpression of AURKA is a major hallmark of epithelial cancers. It encodes the multifunctional serine/threonine kinase aurora A, which is activated at metaphase and is required for cell cycle progression; assessing its activation in living cells is mandatory for next-generation drug design. We describe here a Förster's resonance energy transfer (FRET) biosensor detecting the conformational changes of aurora kinase A induced by its autophosphorylation on Thr288. The biosensor functionally replaces the endogenous kinase in cells and allows the activation of the kinase to be followed throughout the cell cycle. Inhibiting the catalytic activity of the kinase prevents the conformational changes of the biosensor. Using this approach, we discover that aurora kinase A activates during G1 to regulate the stability of microtubules in cooperation with TPX2 and CEP192. These results demonstrate that the aurora kinase A biosensor is a powerful tool to identify new regulatory pathways controlling aurora kinase A activation.

  20. A FRET biosensor reveals spatiotemporal activation and functions of aurora kinase A in living cells

    PubMed Central

    Bertolin, Giulia; Sizaire, Florian; Herbomel, Gaëtan; Reboutier, David; Prigent, Claude; Tramier, Marc

    2016-01-01

    Overexpression of AURKA is a major hallmark of epithelial cancers. It encodes the multifunctional serine/threonine kinase aurora A, which is activated at metaphase and is required for cell cycle progression; assessing its activation in living cells is mandatory for next-generation drug design. We describe here a Förster's resonance energy transfer (FRET) biosensor detecting the conformational changes of aurora kinase A induced by its autophosphorylation on Thr288. The biosensor functionally replaces the endogenous kinase in cells and allows the activation of the kinase to be followed throughout the cell cycle. Inhibiting the catalytic activity of the kinase prevents the conformational changes of the biosensor. Using this approach, we discover that aurora kinase A activates during G1 to regulate the stability of microtubules in cooperation with TPX2 and CEP192. These results demonstrate that the aurora kinase A biosensor is a powerful tool to identify new regulatory pathways controlling aurora kinase A activation. PMID:27624869

  1. Measurements of right / left hemisphere activation using functional near-infrared spectroscopy during incongruent Stroop test.

    PubMed

    Hiroyasu, Tomoyuki; Fukuhara, Michihiro; Yokouchi, Hisatake; Miki, Mitsunori; Yoshimi, Masato

    2011-01-01

    The human brain automatically processes information at multiple sites when recognizing various types of information at the same time, such as color, shape, etc. Cognitive conflict may occur when conflicting information is recognized at the same time. Functional near-infrared spectroscopy (fNIRS) is often used to examine the brain activity associated with this phenomenon. To examine activation of the visual system, we measured brain activity in the right / left hemispheres during cognitive conflict in the Stroop test. Consistent with the results reported previously by Ehlis, the brain activity in the near inferior-frontal gyrus of the left hemisphere was increased during the incongruent task. The brain activity also increased in the near inferior-frontal gyrus of the right hemisphere during the incongruent task. These results indicated that fNIRS can be used to detect brain activity in the inferior-frontal gyrus of the right / left hemispheres during the Stroop test.

  2. Hydrodynamics-Based Functional Forms of Activity Metabolism: A Case for the Power-Law Polynomial Function in Animal Swimming Energetics

    PubMed Central

    Papadopoulos, Anthony

    2009-01-01

    The first-degree power-law polynomial function is frequently used to describe activity metabolism for steady swimming animals. This function has been used in hydrodynamics-based metabolic studies to evaluate important parameters of energetic costs, such as the standard metabolic rate and the drag power indices. In theory, however, the power-law polynomial function of any degree greater than one can be used to describe activity metabolism for steady swimming animals. In fact, activity metabolism has been described by the conventional exponential function and the cubic polynomial function, although only the power-law polynomial function models drag power since it conforms to hydrodynamic laws. Consequently, the first-degree power-law polynomial function yields incorrect parameter values of energetic costs if activity metabolism is governed by the power-law polynomial function of any degree greater than one. This issue is important in bioenergetics because correct comparisons of energetic costs among different steady swimming animals cannot be made unless the degree of the power-law polynomial function derives from activity metabolism. In other words, a hydrodynamics-based functional form of activity metabolism is a power-law polynomial function of any degree greater than or equal to one. Therefore, the degree of the power-law polynomial function should be treated as a parameter, not as a constant. This new treatment not only conforms to hydrodynamic laws, but also ensures correct comparisons of energetic costs among different steady swimming animals. Furthermore, the exponential power-law function, which is a new hydrodynamics-based functional form of activity metabolism, is a special case of the power-law polynomial function. Hence, the link between the hydrodynamics of steady swimming and the exponential-based metabolic model is defined. PMID:19333397

  3. Differential activation of an identified motor neuron and neuromodulation provide Aplysia's retractor muscle an additional function.

    PubMed

    McManus, Jeffrey M; Lu, Hui; Cullins, Miranda J; Chiel, Hillel J

    2014-08-15

    To survive, animals must use the same peripheral structures to perform a variety of tasks. How does a nervous system employ one muscle to perform multiple functions? We addressed this question through work on the I3 jaw muscle of the marine mollusk Aplysia californica's feeding system. This muscle mediates retraction of Aplysia's food grasper in multiple feeding responses and is innervated by a pool of identified neurons that activate different muscle regions. One I3 motor neuron, B38, is active in the protraction phase, rather than the retraction phase, suggesting the muscle has an additional function. We used intracellular, extracellular, and muscle force recordings in several in vitro preparations as well as recordings of nerve and muscle activity from intact, behaving animals to characterize B38's activation of the muscle and its activity in different behavior types. We show that B38 specifically activates the anterior region of I3 and is specifically recruited during one behavior, swallowing. The function of this protraction-phase jaw muscle contraction is to hold food; thus the I3 muscle has an additional function beyond mediating retraction. We additionally show that B38's typical activity during in vivo swallowing is insufficient to generate force in an unmodulated muscle and that intrinsic and extrinsic modulation shift the force-frequency relationship to allow contraction. Using methods that traverse levels from individual neuron to muscle to intact animal, we show how regional muscle activation, differential motor neuron recruitment, and neuromodulation are key components in Aplysia's generation of multifunctionality.

  4. Protein kinase C activity and the relations between blood lead and neurobehavioral function in lead workers.

    PubMed Central

    Hwang, Kyu-Yoon; Lee, Byung-Kook; Bressler, Joseph P; Bolla, Karen I; Stewart, Walter F; Schwartz, Brian S

    2002-01-01

    At picomolar concentrations, lead activates protein kinase C (PKC). This activation has been implicated in the neurotoxicity of lead. No prior study has evaluated the association of PKC activity with neurobehavioral function in humans. The purpose of this study was to determine whether PKC activity is associated with neurobehavioral function or modifies the relationship between blood lead levels and neurobehavioral test scores. In this cross-sectional study of 212 current lead workers in the Republic of Korea, we assessed blood lead levels, neurobehavioral test scores, and PKC activity. PKC activity was determined by measuring the levels of phosphorylation of three erythrocyte membrane proteins (spectrin and the 52-kDa and 48-kDa subunits of band 4.9), using an in vitro back-phosphorylation assay. When linear regression was used to control for confounding variables, blood lead was a significant predictor of decrements in performance on tests of psychomotor function, manual dexterity, and executive ability. In linear regression models, back-phosphorylation levels were not associated with neurobehavioral test scores, but when dichotomized at the median, back-phosphorylation levels modified the relationship between blood lead and test scores. For spectrin and the 52-kDa and 48-kDa subunits of band 4.9, 5, 2, and 5 of 14 interaction terms, respectively, had associated p-values less than 0.10, all with positive signs, indicating that blood lead was associated with worse test scores only in subjects with lower back-phosphorylation levels. These data indicate that blood lead levels are associated with decrements in neurobehavioral test scores, mainly in the domains of manual dexterity and psychomotor function, but only in subjects with lower in vitro back-phosphorylation levels, which is equivalent to higher in vivo PKC activity. We hypothesize that subjects with higher PKC activity in the presence of lead may be more susceptible to the health effects of lead. PMID

  5. Protein kinase C activity and the relations between blood lead and neurobehavioral function in lead workers.

    PubMed

    Hwang, Kyu-Yoon; Lee, Byung-Kook; Bressler, Joseph P; Bolla, Karen I; Stewart, Walter F; Schwartz, Brian S

    2002-02-01

    At picomolar concentrations, lead activates protein kinase C (PKC). This activation has been implicated in the neurotoxicity of lead. No prior study has evaluated the association of PKC activity with neurobehavioral function in humans. The purpose of this study was to determine whether PKC activity is associated with neurobehavioral function or modifies the relationship between blood lead levels and neurobehavioral test scores. In this cross-sectional study of 212 current lead workers in the Republic of Korea, we assessed blood lead levels, neurobehavioral test scores, and PKC activity. PKC activity was determined by measuring the levels of phosphorylation of three erythrocyte membrane proteins (spectrin and the 52-kDa and 48-kDa subunits of band 4.9), using an in vitro back-phosphorylation assay. When linear regression was used to control for confounding variables, blood lead was a significant predictor of decrements in performance on tests of psychomotor function, manual dexterity, and executive ability. In linear regression models, back-phosphorylation levels were not associated with neurobehavioral test scores, but when dichotomized at the median, back-phosphorylation levels modified the relationship between blood lead and test scores. For spectrin and the 52-kDa and 48-kDa subunits of band 4.9, 5, 2, and 5 of 14 interaction terms, respectively, had associated p-values less than 0.10, all with positive signs, indicating that blood lead was associated with worse test scores only in subjects with lower back-phosphorylation levels. These data indicate that blood lead levels are associated with decrements in neurobehavioral test scores, mainly in the domains of manual dexterity and psychomotor function, but only in subjects with lower in vitro back-phosphorylation levels, which is equivalent to higher in vivo PKC activity. We hypothesize that subjects with higher PKC activity in the presence of lead may be more susceptible to the health effects of lead.

  6. Screening SIRT1 Activators from Medicinal Plants as Bioactive Compounds against Oxidative Damage in Mitochondrial Function

    PubMed Central

    Wang, Yi; Liang, Xinying; Chen, Yaqi; Zhao, Xiaoping

    2016-01-01

    Sirtuin type 1 (SIRT1) belongs to the family of NAD+ dependent histone deacetylases and plays a critical role in cellular metabolism and response to oxidative stress. Traditional Chinese medicines (TCMs), as an important part of natural products, have been reported to exert protective effect against oxidative stress in mitochondria. In this study, we screened SIRT1 activators from TCMs and investigated their activities against mitochondrial damage. 19 activators were found in total by in vitro SIRT1 activity assay. Among those active compounds, four compounds, ginsenoside Rb2, ginsenoside F1, ginsenoside Rc, and schisandrin A, were further studied to validate the SIRT1-activation effects by liquid chromatography-mass spectrometry and confirm their activities against oxidative damage in H9c2 cardiomyocytes exposed to tert-butyl hydroperoxide (t-BHP). The results showed that those compounds enhanced the deacetylated activity of SIRT1, increased ATP content, and inhibited intracellular ROS formation as well as regulating the activity of Mn-SOD. These SIRT1 activators also showed moderate protective effects on mitochondrial function in t-BHP cells by recovering oxygen consumption and increasing mitochondrial DNA content. Our results suggested that those compounds from TCMs attenuated oxidative stress-induced mitochondrial damage in cardiomyocytes through activation of SIRT1. PMID:26981165

  7. Human T lymphocytes express N-methyl-D-aspartate receptors functionally active in controlling T cell activation

    SciTech Connect

    Miglio, Gianluca; Varsaldi, Federica; Lombardi, Grazia . E-mail: lombardi@pharm.unipmn.it

    2005-12-30

    The aim of this study was to investigate the expression and the functional role of N-methyl-D-aspartate (NMDA) receptors in human T cells. RT-PCR analysis showed that human resting peripheral blood lymphocytes (PBL) and Jurkat T cells express genes encoding for both NR1 and NR2B subunits: phytohemagglutinin (PHA)-activated PBL also expresses both these genes and the NR2A and NR2D genes. Cytofluorimetric analysis showed that NR1 expression increases as a consequence of PHA (10 {mu}g/ml) treatment. D-(-)-2-Amino-5-phosphonopentanoic acid (D-AP5), and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine [(+)-MK 801], competitive and non-competitive NMDA receptor antagonists, respectively, inhibited PHA-induced T cell proliferation, whereas they did not affect IL-2 (10 U/ml)-induced proliferation of PHA blasts. These effects were due to the prevention of T cell activation (inhibition of cell aggregate formation and CD25 expression), but not to cell cycle arrest or death. These results demonstrate that human T lymphocytes express NMDA receptors, which are functionally active in controlling cell activation.

  8. Functional and cardioprotective effects of simultaneous and individual activation of protein kinase A and Epac

    PubMed Central

    Bond, Mark; James, Andrew F; Dyar, Zara; Amini, Raheleh; Johnson, Jason L; Suleiman, M‐Saadeh

    2017-01-01

    Background and Purpose Myocardial cAMP elevation confers cardioprotection against ischaemia/reperfusion (I/R) injury. cAMP activates two independent signalling pathways, PKA and Epac. This study investigated the cardiac effects of activating PKA and/or Epac and their involvement in cardioprotection against I/R. Experimental Approach Hearts from male rats were used either for determination of PKA and PKC activation or perfused in the Langendorff mode for either cardiomyocyte isolation or used to monitor functional activity at basal levels and after 30 min global ischaemia and 2 h reperfusion. Functional recovery and myocardial injury during reperfusion (LDH release and infarct size) were evaluated. Activation of PKA and/or Epac in perfused hearts was induced using cell permeable cAMP analogues in the presence or absence of inhibitors of PKA, Epac and PKC. H9C2 cells and cardiomyocytes were used to assess activation of Epac and effect on Ca2+ transients. Key Results Selective activation of either PKA or Epac was found to trigger a positive inotropic effect, which was considerably enhanced when both pathways were simultaneously activated. Only combined activation of PKA and Epac induced marked cardioprotection against I/R injury. This was accompanied by PKCε activation and repressed by inhibitors of PKA, Epac or PKC. Conclusion and Implications Simultaneous activation of both PKA and Epac induces an additive inotropic effect and confers optimal and marked cardioprotection against I/R injury. The latter effect is mediated by PKCε activation. This work has introduced a new therapeutic approach and targets to protect the heart against cardiac insults. PMID:28071786

  9. Functional Interplay between CBP and PCAF in Acetylation and Regulation of Transcription Factor KLF13 Activity

    PubMed Central

    Song, Chao-Zhong; Keller, Kimberly; Chen, Yangchao; Stamatoyannopoulos, George

    2010-01-01

    The transcriptional co-activators CBP/p300 and PCAF participate in transcriptional activation by many factors. We have shown that both CBP/p300 and PCAF stimulate the transcriptional activation by KLF13, a member of the KLF/Sp1 family, either individually or cooperatively. Here we further investigated how CBP and PCAF acetylation regulate KLF13 activity, and how these two co-activators functionally interplay in the regulation of KLF13 activity. We found that CBP and PCAF acetylated KLF13 at specific lysine residues in the zinc finger domain of KLF13. The acetylation by CBP, however, resulted in disruption of KLF13 DNA binding. Although the acetyltransferase activity of CBP is not required for stimulating the DNA binding activity of all of the transcription factors that we have examined, the disruption of factor DNA binding by CBP acetylation is factor-specific. We further showed that PCAF and CBP act synergistically and antagonistically to regulate KLF13 DNA binding depending on the status of acetylation. PCAF blocked CBP acetylation and disruption of KLF13 DNA binding. Conversely, acetylation of KLF13 by CBP prevented PCAF stimulation of KLF13 DNA binding. PCAF blocked CBP disruption of KLF13 DNA binding by preventing CBP acetylation of KLF13. These results demonstrate that acetylation by CBP has distinct effects on transcription factor DNA binding, and that CBP and PCAF regulate each other functionally in their regulation of transcription factor DNA binding. PMID:12758070

  10. The c-Jun kinase signaling cascade promotes glial engulfment activity through activation of draper and phagocytic function.

    PubMed

    Macdonald, J M; Doherty, J; Hackett, R; Freeman, M R

    2013-09-01

    After neuronal injury or death glial cells become reactive, exhibiting dramatic changes in morphology and patterns of gene expression and ultimately engulfing neuronal debris. Rapid clearance of degenerating neuronal material is thought to be crucial for suppression of inflammation and promotion of functional recovery. Here we demonstrate that Drosophila c-Jun N-terminal kinase (dJNK) signaling is a critical in vivo mediator of glial engulfment activity. In response to axotomy, we find glial dJNK signals through a cascade involving the upstream mitogen-activated protein kinase kinase kinases Slipper and Tak1, the mitogen-activated protein kinase kinase MKK4, and ultimately the Drosophila activator protein 1 (AP-1) transcriptional complex composed of Jra and Kayak to initiate glial phagocytosis of degenerating axons. Interestingly, loss of dJNK also blocked injury-induced upregulation of Draper levels in glia, and glial-specific overexpression of Draper was sufficient to rescue engulfment defects associated with loss of dJNK signaling. This work identifies that the dJNK pathway is a novel mediator of glial engulfment activity and a primary role for the glial Slipper/Tak1 →MKK4 →dJNK →dAP-1 signaling cascade appears to be activation of draper expression after axon injury.

  11. Prediction of cloud condensation nuclei activity for organic compounds using functional group contribution methods

    DOE PAGES

    Petters, M. D.; Kreidenweis, S. M.; Ziemann, P. J.

    2016-01-19

    A wealth of recent laboratory and field experiments demonstrate that organic aerosol composition evolves with time in the atmosphere, leading to changes in the influence of the organic fraction to cloud condensation nuclei (CCN) spectra. There is a need for tools that can realistically represent the evolution of CCN activity to better predict indirect effects of organic aerosol on clouds and climate. This work describes a model to predict the CCN activity of organic compounds from functional group composition. Following previous methods in the literature, we test the ability of semi-empirical group contribution methods in Köhler theory to predict themore » effective hygroscopicity parameter, kappa. However, in our approach we also account for liquid–liquid phase boundaries to simulate phase-limited activation behavior. Model evaluation against a selected database of published laboratory measurements demonstrates that kappa can be predicted within a factor of 2. Simulation of homologous series is used to identify the relative effectiveness of different functional groups in increasing the CCN activity of weakly functionalized organic compounds. Hydroxyl, carboxyl, aldehyde, hydroperoxide, carbonyl, and ether moieties promote CCN activity while methylene and nitrate moieties inhibit CCN activity. The model can be incorporated into scale-bridging test beds such as the Generator of Explicit Chemistry and Kinetics of Organics in the Atmosphere (GECKO-A) to evaluate the evolution of kappa for a complex mix of organic compounds and to develop suitable parameterizations of CCN evolution for larger-scale models.« less

  12. Prediction of cloud condensation nuclei activity for organic compounds using functional group contribution methods

    NASA Astrophysics Data System (ADS)

    Petters, M. D.; Kreidenweis, S. M.; Ziemann, P. J.

    2016-01-01

    A wealth of recent laboratory and field experiments demonstrate that organic aerosol composition evolves with time in the atmosphere, leading to changes in the influence of the organic fraction to cloud condensation nuclei (CCN) spectra. There is a need for tools that can realistically represent the evolution of CCN activity to better predict indirect effects of organic aerosol on clouds and climate. This work describes a model to predict the CCN activity of organic compounds from functional group composition. Following previous methods in the literature, we test the ability of semi-empirical group contribution methods in Köhler theory to predict the effective hygroscopicity parameter, kappa. However, in our approach we also account for liquid-liquid phase boundaries to simulate phase-limited activation behavior. Model evaluation against a selected database of published laboratory measurements demonstrates that kappa can be predicted within a factor of 2. Simulation of homologous series is used to identify the relative effectiveness of different functional groups in increasing the CCN activity of weakly functionalized organic compounds. Hydroxyl, carboxyl, aldehyde, hydroperoxide, carbonyl, and ether moieties promote CCN activity while methylene and nitrate moieties inhibit CCN activity. The model can be incorporated into scale-bridging test beds such as the Generator of Explicit Chemistry and Kinetics of Organics in the Atmosphere (GECKO-A) to evaluate the evolution of kappa for a complex mix of organic compounds and to develop suitable parameterizations of CCN evolution for larger-scale models.

  13. Revisiting the mechanism of coagulation factor XIII activation and regulation from a structure/functional perspective

    PubMed Central

    Gupta, Sneha; Biswas, Arijit; Akhter, Mohammad Suhail; Krettler, Christoph; Reinhart, Christoph; Dodt, Johannes; Reuter, Andreas; Philippou, Helen; Ivaskevicius, Vytautas; Oldenburg, Johannes

    2016-01-01

    The activation and regulation of coagulation Factor XIII (FXIII) protein has been the subject of active research for the past three decades. Although discrete evidence exists on various aspects of FXIII activation and regulation a combinatorial structure/functional view in this regard is lacking. In this study, we present results of a structure/function study of the functional chain of events for FXIII. Our study shows how subtle chronological submolecular changes within calcium binding sites can bring about the detailed transformation of the zymogenic FXIII to its activated form especially in the context of FXIIIA and FXIIIB subunit interactions. We demonstrate what aspects of FXIII are important for the stabilization (first calcium binding site) of its zymogenic form and the possible modes of deactivation (thrombin mediated secondary cleavage) of the activated form. Our study for the first time provides a structural outlook of the FXIIIA2B2 heterotetramer assembly, its association and dissociation. The FXIIIB subunits regulatory role in the overall process has also been elaborated upon. In summary, this study provides detailed structural insight into the mechanisms of FXIII activation and regulation that can be used as a template for the development of future highly specific therapeutic inhibitors targeting FXIII in pathological conditions like thrombosis. PMID:27453290

  14. Functional interrelationships in the alkaline phosphatase superfamily: phosphodiesterase activity of Escherichia coli alkaline phosphatase.

    PubMed

    O'Brien, P J; Herschlag, D

    2001-05-15

    sulfatase activity, further establishing the functional interrelationships among the sulfatases, phosphatases, and phosphodiesterases within the evolutionarily related AP superfamily. The catalytic promiscuity of AP could have facilitated divergent evolution via gene duplication by providing a selective advantage upon which natural selection could have acted.

  15. Task Control Signals in Pediatric Tourette Syndrome Show Evidence of Immature and Anomalous Functional Activity

    PubMed Central

    Church, Jessica A.; Wenger, Kristin K.; Dosenbach, Nico U. F.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

    2009-01-01

    Tourette Syndrome (TS) is a pediatric movement disorder that may affect control signaling in the brain. Previous work has proposed a dual-networks architecture of control processing involving a task-maintenance network and an adaptive control network (Dosenbach et al., 2008). A prior resting-state functional connectivity MRI (rs-fcMRI) analysis in TS has revealed functional immaturity in both putative control networks, with “anomalous” correlations (i.e., correlations outside the typical developmental range) limited to the adaptive control network (Church et al., 2009). The present study used functional MRI (fMRI) to study brain activity related to adaptive control (by studying start-cues signals), and to task-maintenance (by studying signals sustained across a task set). Two hypotheses from the previous rs-fcMRI results were tested. First, adaptive control (i.e., start-cue) activity will be altered in TS, including activity inconsistent with typical development (“anomalous”). Second, group differences found in task-maintenance (i.e., sustained) activity will be consistent with functional immaturity in TS. We examined regions found through a direct comparison of adolescents with and without TS, as well as regions derived from a previous investigation that showed differences between unaffected children and adults. The TS group showed decreased start-cue signal magnitude in regions where start-cue activity is unchanged over typical development, consistent with anomalous adaptive control. The TS group also had higher magnitude sustained signals in frontal cortex regions that overlapped with regions showing differences over typical development, consistent with immature task-maintenance in TS. The results demonstrate task-related fMRI signal differences anticipated by the atypical functional connectivity found previously in adolescents with TS, strengthening the evidence for functional immaturity and anomalous signaling in control networks in adolescents with TS

  16. Functional Genetic Variation in Dopamine Signaling Moderates Prefrontal Cortical Activity During Risky Decision Making

    PubMed Central

    Kohno, Milky; Nurmi, Erika L; Laughlin, Christopher P; Morales, Angelica M; Gail, Emma H; Hellemann, Gerhard S; London, Edythe D

    2016-01-01

    Brain imaging has revealed links between prefrontal activity during risky decision-making and striatal dopamine receptors. Specifically, striatal dopamine D2-like receptor availability is correlated with risk-taking behavior and sensitivity of prefrontal activation to risk in the Balloon Analogue Risk Task (BART). The extent to which these associations, involving a single neurochemical measure, reflect more general effects of dopaminergic functioning on risky decision making, however, is unknown. Here, 65 healthy participants provided genotypes and performed the BART during functional magnetic resonance imaging. For each participant, dopamine function was assessed using a gene composite score combining known functional variation across five genes involved in dopaminergic signaling: DRD2, DRD3, DRD4, DAT1, and COMT. The gene composite score was negatively related to dorsolateral prefrontal cortical function during risky decision making, and nonlinearly related to earnings on the task. Iterative permutations of all possible allelic variations (7777 allelic combinations) was tested on brain function in an independently defined region of the prefrontal cortex and confirmed empirical validity of the composite score, which yielded stronger association than 95% of all other possible combinations. The gene composite score also accounted for a greater proportion of variability in neural and behavioral measures than the independent effects of each gene variant, indicating that the combined effects of functional dopamine pathway genes can provide a robust assessment, presumably reflecting the cumulative and potentially interactive effects on brain function. Our findings support the view that the links between dopaminergic signaling, prefrontal function, and decision making vary as a function of dopamine signaling capacity. PMID:26119471

  17. Objectively-Measured Physical Activity and Cognitive Functioning in Breast Cancer Survivors

    PubMed Central

    Marinac, Catherine R.; Godbole, Suneeta; Kerr, Jacqueline; Natarajan, Loki; Patterson, Ruth E.; Hartman, Sheri J.

    2015-01-01

    Purpose To explore the relationship between objectively measured physical activity and cognitive functioning in breast cancer survivors. Methods Participants were 136 postmenopausal breast cancer survivors. Cognitive functioning was assessed using a comprehensive computerized neuropsychological test. 7-day physical activity was assessed using hip-worn accelerometers. Linear regression models examined associations of minutes per day of physical activity at various intensities on individual cognitive functioning domains. The partially adjusted model controlled for primary confounders (model 1), and subsequent adjustments were made for chemotherapy history (model 2), and BMI (model 3). Interaction and stratified models examined BMI as an effect modifier. Results Moderate-to-vigorous physical activity (MVPA) was associated with Information Processing Speed. Specifically, ten minutes of MVPA was associated with a 1.35-point higher score (out of 100) on the Information Processing Speed domain in the partially adjusted model, and a 1.29-point higher score when chemotherapy was added to the model (both p<.05). There was a significant BMI x MVPA interaction (p=.051). In models stratified by BMI (<25 vs. ≥25 kg/m2), the favorable association between MVPA and Information Processing Speed was stronger in the subsample of overweight and obese women (p<.05), but not statistically significant in the leaner subsample. Light-intensity physical activity was not significantly associated with any of the measured domains of cognitive function. Conclusions MVPA may have favorable effects on Information Processing Speed in breast cancer survivors, particularly among overweight or obese women. Implications for Cancer Survivors Interventions targeting increased physical activity may enhance aspects of cognitive function among breast cancer survivors. PMID:25304986

  18. Soluble Milk Protein Supplementation with Moderate Physical Activity Improves Locomotion Function in Aging Rats

    PubMed Central

    Lafoux, Aude; Baudry, Charlotte; Bonhomme, Cécile; Le Ruyet, Pascale; Huchet, Corinne

    2016-01-01

    Aging is associated with a loss of muscle mass and functional capacity. Present study was designed to compare the impact of specific dairy proteins on muscular function with or without a low-intensity physical activity program on a treadmill in an aged rat model. We investigated the effects of nutritional supplementation, five days a week over a 2-month period with a slow digestible protein, casein or fast digestible proteins, whey or soluble milk protein, on strength and locomotor parameters in sedentary or active aged Wistar RjHan rats (17–19 months of age). An extensive gait analysis was performed before and after protein supplementation. After two months of protein administration and activity program, muscle force was evaluated using a grip test, spontaneous activity using an open-field and muscular mass by specific muscle sampling. When aged rats were supplemented with proteins without exercise, only minor effects of different diets on muscle mass and locomotion were observed: higher muscle mass in the casein group and improvement of stride frequencies with soluble milk protein. By contrast, supplementation with soluble milk protein just after physical activity was more effective at improving overall skeletal muscle function in old rats compared to casein. For active old rats supplemented with soluble milk protein, an increase in locomotor activity in the open field and an enhancement of static and dynamic gait parameters compared to active groups supplemented with casein or whey were observed without any differences in muscle mass and forelimb strength. These results suggest that consumption of soluble milk protein as a bolus immediately after a low intensity physical activity may be a suitable nutritional intervention to prevent decline in locomotion in aged rats and strengthen the interest to analyze the longitudinal aspect of locomotion in aged rodents. PMID:27973615

  19. Direct activation and anti-repression functions of GAL4-VP16 use distinct molecular mechanisms.

    PubMed Central

    Lyons, J G; Chambon, P

    1995-01-01

    In order to determine whether the molecular mechanisms used for direct activation by GAL4-VP16 are the same as those used for anti-repression, we have employed monoclonal antibodies specific for the VP16 activation domain. In the absence of added repressors, GAL4-VP16 was able to stimulate transcription from a template containing GAL4-binding sites, and the antibodies raised against the VP16 activation domain failed to inhibit this direct activation. GAL4-VP16 also was able to prevent histone H1-mediated repression by a mechanism that was strongly dependent on the presence of specific GAL4-binding elements in the promoter. However, in contrast to the assays conducted in the absence of repressors, the antibodies were strong inhibitors of GAL4-VP16-activated transcription in the presence of histone H1. Thus the binding of the antibodies distinguished between the direct activation and anti-repression functions of GAL4-VP16, indicating that these functions operate through distinct molecular mechanisms. The anti-repression-specific mechanism that is inhibitable by the antibodies acted at an early stage of preinitiation complex formation. Deletions of individual subdomains of the VP16 activation domain demonstrated that there was not a discrete subdomain responsible for the anti-repression function of GAL4-VP16. Thus, the inhibitory effect of the antibodies appeared to be due to the location of the epitope within the activator protein rather than to some inherent biochemical property of that region of the protein that is required specifically for anti-repression. The inhibitory effect of the antibodies also ruled out the possibility that steric exclusion of repressor proteins from the promoter was the sole means of anti-repression by the transcriptional activator. Images Figure 1 Figure 2 PMID:8554536

  20. Executive control function, brain activation and white matter hyperintensities in older adults

    PubMed Central

    Venkatraman, Vijay K.; Aizenstein, Howard; Guralnik, Jack; Newman, Anne B.; Glynn, Nancy W.; Taylor, Christopher; Studenski, Stephanie; Launer, Lenore; Pahor, Marco; Williamson, Jeff; Rosano, Caterina

    2009-01-01

    Context Older adults responding to executive control function (ECF) tasks show greater brain activation on functional MRI (fMRI). It is not clear whether greater fMRI activation indicates a strategy to compensate for underlying brain structural abnormalities while maintaining higher performance. Objective To identify the patterns of fMRI activation in relationship with ECF performance and with brain structural abnormalities. Design Cross-sectional analysis. Main variables of interest: fMRI activation, accuracy while performing an ECF task (Digit Symbol Substitution Test), volume of white matter hyperintensities and of total brain atrophy. Setting Cohort of community-dwelling older adults. Participants Data were obtained on 25 older adults (20 women, 81 years mean age). Outcome Measure Accuracy (number of correct response / total number of responses) while performing the Digit Symbol Substitution Test. Results Greater accuracy was significantly associated with greater peak fMRI activation, from ECF regions, including left middle frontal gyrus and right posterior parietal cortex. Greater WMH was associated with lower activation within accuracy-related regions. The interaction of accuracy by white matter hyperintensities volume was significant within the left posterior parietal region. Specifically, the correlation of white matter hyperintensities volume with fMRI activation varied as a function of accuracy and it was positive for greater accuracy. Associations with brain atrophy were not significant. Conclusions Recruitment of additional areas and overall greater brain activation in older adults is associated with higher performance. Posterior parietal activation may be particularly important to maintain higher accuracy in the presence of underlying brain connectivity structural abnormalities. PMID:19922803

  1. AMPK up-activation reduces motility and regulates other functions of boar spermatozoa.

    PubMed

    Hurtado de Llera, A; Martin-Hidalgo, D; Gil, M C; Garcia-Marin, L J; Bragado, M J

    2015-01-01

    We recently demonstrated that AMPK inhibition in spermatozoa regulates motility, plasma membrane organization, acrosome integrity and mitochondrial membrane potential. As AMPK activity varies in different energy conditions induced by sperm environment, this work investigates the functional effects of AMPK activation in boar spermatozoa. Spermatozoa were incubated under non-stimulating (TBM) or Ca(2+) and [Formula: see text]-stimulating (TCM) media in the presence/absence of AMPK activator, A769662, for different times. AMPK activity, evaluated as Thr(172) phosphorylation by western blot, is effectively increased by A769662 in spermatozoa. AMPK activation significantly reduces the percentage of motile spermatozoa under Ca(2+) and/or [Formula: see text]-stimulating conditions. Moreover, AMPK activation in spermatozoa incubated in TBM or TCM significantly reduces curvilinear VCL, straight-line VSL and average VAP velocities, which subsequently lead to a significant decrease in the percentage of rapid spermatozoa (VAP > 80 μm/s). The effect of AMPK activation on motility is intensified by the absence of BSA in the incubation medium. AMPK activation for a short time prevents the decline in cell viability and in the sperm population displaying high mitochondrial membrane potential which is induced by Ca(2+) and [Formula: see text]. Sustained (24 h) AMPK activation under TBM or TCM significantly increases both lipid disorganization and phosphatidylserine externalization in the sperm plasma membrane, and diminishes the acrosome membrane integrity. In summary, AMPK activation modifies essential sperm processes such as motility, viability, mitochondrial membrane potential, acrosome membrane integrity, and organization and fluidity of plasma membrane. As these spermatozoa processes are required under different environmental conditions when transiting through the female reproductive tract to achieve fertilization, we conclude that balanced levels of AMPK activity are

  2. Structural and functional brain changes related to different types of physical activity across the life span.

    PubMed

    Voelcker-Rehage, Claudia; Niemann, Claudia

    2013-11-01

    Physical activity has been shown to improve cognitive functioning. Research has largely focused on cognitive facilitation by cardiovascular exercise in older adults. Only few studies have investigated younger age groups or other types of physical activity. In this paper we review and summarize common results found in recent studies of metabolic (i.e. cardiovascular and resistance) and coordinative exercise. Findings from human motor learning are utilized to complement results on coordinative exercise. Results show that both types of exercise affect the brain differently. We propose possible mechanisms by which physical activity facilitates cognitive performance by briefly reviewing microscopic structural changes in animal research. Lastly, we highlight open research questions.

  3. Dual function of suppressor of fused in Hh pathway activation and mouse spinal cord patterning.

    PubMed

    Liu, Jinling; Heydeck, Westley; Zeng, Huiqing; Liu, Aimin

    2012-02-15

    The morphogen Sonic hedgehog, one of the Hedgehog (Hh) family of secreted proteins, plays a key role in patterning the mammalian spinal cord along its dorsoventral (D/V) axis through the activation of Glioma-associated oncogene (Gli) family of transcription factors. Suppressor of Fused (Sufu), a Gli-interacting protein, modulates the D/V patterning of the spinal cord by antagonizing Hh signaling. The molecular mechanisms underlying the function of Sufu in Hh pathway activation and spinal cord D/V patterning remain controversial, particularly in light of recent findings that Sufu protects Gli2 and Gli3 proteins from proteasomal degradation. In the current study, we show that Hh pathway activation and dorsal expansion of ventral spinal cord cell types in the absence of Sufu depend on the activator activities of all three Gli family proteins. We also show that Sufu plays a positive role in the maximal activation of Hh signaling that defines the ventral-most cell fate in the mammalian spinal cord, likely through protecting Gli2 and Gli3 proteins from degradation. Finally, by altering the level of Gli3 repressor on a background of reduced Gli activator activities, we reveal an important contribution of Gli3 repressor activity to the Hh pathway activation and the D/V patterning of the spinal cord.

  4. Hop derived flavonoid xanthohumol inhibits endothelial cell functions via AMPK activation.

    PubMed

    Gallo, Cristina; Dallaglio, Katiuscia; Bassani, Barbara; Rossi, Teresa; Rossello, Armando; Noonan, Douglas M; D'Uva, Gabriele; Bruno, Antonino; Albini, Adriana

    2016-09-13

    Angiogenesis, a process characterized by the formation of new blood vessels from pre-existing ones, is a crucial step in tumor growth and dissemination. Recently, increased attention has been addressed to the ability of flavonoids to prevent cancer by suppressing angiogenesis, strategy that we named "angioprevention". Several natural compounds exert their anti-tumor properties by activating 5' adenosine monophosphate-activated protein kinase (AMPK), a key regulator of metabolism in cancer cells. Drugs with angiopreventive activities, in particular metformin, regulate AMPK in endothelial cells. Here we investigated the involvement of AMPK in the anti-angiogenic effects of xanthohumol (XN), the major prenylated flavonoid of the hop plant, and mechanisms of action. The anti-angiogenic activity of XN was more potent than epigallocatechin-3-gallate (EGCG). Treatment of endothelial cells with XN led to increased AMPK phosphorylation and activity. Functional studies using biochemical approaches confirmed that AMPK mediates XN anti-angiogenic activity. AMPK activation by XN was mediated by CAMMKβ, but not LKB1. Analysis of the downstream mechanisms showed that XN-induced AMPK activation reduced nitric oxide (NO) levels in endothelial cells by decreasing eNOS phosphorylation. Finally, AKT pathway was inactivated by XN as part of its anti-angiogenic activity, but independently from AMPK, suggesting that these two signaling pathways proceed autonomously. Our study dissects the molecular mechanism by which XN exerts its potent anti-angiogenic activity, pointing out AMPK as a crucial signal transducer.

  5. Hop derived flavonoid xanthohumol inhibits endothelial cell functions via AMPK activation

    PubMed Central

    Gallo, Cristina; Dallaglio, Katiuscia; Bassani, Barbara; Rossi, Teresa; Rossello, Armando; Noonan, Douglas M.; D'Uva, Gabriele; Bruno, Antonino; Albini, Adriana

    2016-01-01

    Angiogenesis, a process characterized by the formation of new blood vessels from pre-existing ones, is a crucial step in tumor growth and dissemination. Recently, increased attention has been addressed to the ability of flavonoids to prevent cancer by suppressing angiogenesis, strategy that we named “angioprevention”. Several natural compounds exert their anti-tumor properties by activating 5′ adenosine monophosphate-activated protein kinase (AMPK), a key regulator of metabolism in cancer cells. Drugs with angiopreventive activities, in particular metformin, regulate AMPK in endothelial cells. Here we investigated the involvement of AMPK in the anti-angiogenic effects of xanthohumol (XN), the major prenylated flavonoid of the hop plant, and mechanisms of action. The anti-angiogenic activity of XN was more potent than epigallocatechin-3-gallate (EGCG). Treatment of endothelial cells with XN led to increased AMPK phosphorylation and activity. Functional studies using biochemical approaches confirmed that AMPK mediates XN anti-angiogenic activity. AMPK activation by XN was mediated by CAMMKβ, but not LKB1. Analysis of the downstream mechanisms showed that XN-induced AMPK activation reduced nitric oxide (NO) levels in endothelial cells by decreasing eNOS phosphorylation. Finally, AKT pathway was inactivated by XN as part of its anti-angiogenic activity, but independently from AMPK, suggesting that these two signaling pathways proceed autonomously. Our study dissects the molecular mechanism by which XN exerts its potent anti-angiogenic activity, pointing out AMPK as a crucial signal transducer. PMID:27494895

  6. Late-stage diversification of biologically active pyridazinones via a direct C-H functionalization strategy.

    PubMed

    Li, Wei; Fan, Zhoulong; Geng, Kaijun; Xu, Youjun; Zhang, Ao

    2015-01-14

    Divergent C-H functionalization reactions (arylation, carboxylation, olefination, thiolation, acetoxylation, halogenation, naphthylation) using a pyridazinone moiety as an internal directing group were successfully established. This approach offers a late-stage, ortho-selective diversification of a biologically active pyridazinone scaffold. Seven series of novel pyridazinone analogues were synthesized conveniently as the synthetic precursors of potential sortase A (SrtA) inhibitors.

  7. Postsynaptic FMRP bidirectionally regulates excitatory synapses as a function of developmental age and MEF2 activity.

    PubMed

    Zang, Tong; Maksimova, Marina A; Cowan, Christopher W; Bassel-Duby, Rhonda; Olson, Eric N; Huber, Kimberly M

    2013-09-01

    Rates of synapse formation and elimination change over the course of postnatal development, but little is known of molecular mechanisms that mediate this developmental switch. Here, we report that the dendritic RNA-binding protein fragile X mental retardation protein (FMRP) bidirectionally and cell autonomously regulates excitatory synaptic function, which depends on developmental age as well as function of the activity-dependent transcription factor myocyte enhancer factor 2 (MEF2). The acute postsynaptic expression of FMRP in CA1 neurons of hippocampal slice cultures (during the first postnatal week, P6-P7) promotes synapse function and maturation. In contrast, the acute expression of FMRP or endogenous FMRP in more mature neurons (during the second postnatal week; P13-P16) suppresses synapse number. The ability of neuronal depolarization to stimulate MEF2 transcriptional activity increases over this same developmental period. Knockout of endogenous MEF2 isoforms causes acute postsynaptic FMRP expression to promote, instead of eliminate, synapses onto 2-week-old neurons. Conversely, the expression of active MEF2 in neonatal neurons results in a precocious FMRP-dependent synapse elimination. Our findings suggest that FMRP and MEF2 function together to fine tune synapse formation and elimination rates in response to neuronal activity levels over the course of postnatal development.

  8. Functional, photochemically active, and chemically asymmetric membranes by interfacial polymerization of derivatized multifunctional prepolymers

    DOEpatents

    Lonsdale, Harold K.; Wamser, Carl C.

    1990-01-01

    The preparation of a novel class of thin film membranes by interfacial polymerization is disclosed, said membranes incorporating as part of their polymeric structure the functionality of monomeric or oligomeric precursors. Specific embodiments include porphyrin and phthalocyanine derivatives that are photochemically or electrochemically active, as well as chemically asymmetric membranes.

  9. Functional, photochemically active, and chemically asymmetric membranes by interfacial polymerization of derivatized multifunctional prepolymers

    DOEpatents

    Lonsdale, H.K.; Wamser, C.C.

    1990-04-17

    The preparation of a novel class of thin film membranes by interfacial polymerization is disclosed, said membranes incorporating as part of their polymeric structure the functionality of monomeric or oligomeric precursors. Specific embodiments include porphyrin and phthalocyanine derivatives that are photochemically or electrochemically active, as well as chemically asymmetric membranes.

  10. Functional, photochemically active, and chemically asymmetric membranes by interfacial polymerization of derivatized multifunctional prepolymers

    DOEpatents

    Lonsdale, Harold K.; Wamser, Carl C.

    1988-01-01

    The preparation of a novel class of thin film membranes by interfacial polymerization is disclosed, said membanes incorporating as part of their polymeric structure the functionality of monomeric or oligomeric precursors. Specific embodiments include porphyrin and phthalocyanime derivatives that are photochemically or electrochemically active, as well as chemically asymmetric membranes.

  11. 20 CFR 641.856 - What functions and activities constitute administrative costs?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false What functions and activities constitute administrative costs? 641.856 Section 641.856 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROVISIONS GOVERNING THE SENIOR COMMUNITY SERVICE EMPLOYMENT PROGRAM...

  12. 20 CFR 641.856 - What functions and activities constitute administrative costs?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false What functions and activities constitute administrative costs? 641.856 Section 641.856 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROVISIONS GOVERNING THE SENIOR COMMUNITY SERVICE EMPLOYMENT PROGRAM...

  13. Gain-Of-Function Mutational Activation of Human TRNA Synthetase Procytokine

    SciTech Connect

    Yang, X.L.; Kapoor, M.; Otero, F.J.; Slike, B.M.; Tsuruta, H.; Frausto, R.; Bates, A.; Ewalt, K.L.; Cheresh, D.A.; Schimmel, P.; /Scripps Res. Inst. /SLAC, SSRL

    2009-04-30

    Disease-causing mutations occur in genes for aminoacyl tRNA synthetases. That some mutations are dominant suggests a gain of function. Native tRNA synthetases, such as tyrosyl-tRNA synthetase (TyrRS) and tryptophanyl-tRNA synthetase, catalyze aminoacylation and are also procytokines that are activated by natural fragmentation. In principle, however, gain-of-function phenotypes could arise from mutational activation of synthetase procytokines. From crystal structure analysis, we hypothesized that a steric block of a critical Glu-Leu-Arg (ELR) motif in full-length TyrRS suppresses the cytokine activity of a natural fragment. To test this hypothesis, we attempted to uncover ELR in the procytokine by mutating a conserved tyrosine (Y341) that tethers ELR. Site-specific proteolytic cleavage and small-angle X-ray scattering established subtle opening of the structure by the mutation. Strikingly, four different assays demonstrated mutational activation of cytokine functions. The results prove the possibilities for constitutive gain-of-function mutations in tRNA synthetases.

  14. Differential Item Functioning Analysis of the 2003-04 NHANES Physical Activity Questionnaire

    ERIC Educational Resources Information Center

    Gao, Yong; Zhu, Weimo

    2011-01-01

    Using differential item functioning (DIF) analyses, this study examined whether there were any DIF items in the National Health and Nutrition Examination Survey (NHANES) physical activity (PA) questionnaire. A subset of adult data from the 2003-04 NHANES study (n = 3,083) was used. PA items related to respondents' occupational, transportation,…

  15. EGFR-AKT-mTOR activation mediates epiregulin-induced pleiotropic functions in cultured osteoblasts.

    PubMed

    Fan, Jian-Bo; Liu, Wei; Zhu, Xin-Hui; Yuan, Kun; Xu, Da-Wei; Chen, Jia-Jia; Cui, Zhi-Ming

    2015-01-01

    Epidermal growth factor (EGF) receptor (EGFR) emerges as an essential molecule for the regulating of osteoblast cellular functions. In the current study, we explored the effect of epiregulin, a new EGFR ligand, on osteoblast functions in vitro, and studied the underlying mechanisms. We found that epiregulin-induced EGFR activation in both primary osteoblasts and osteoblast-like MC3T3-E1 cells. Meanwhile, epiregulin activated AKT-mammalian target of rapamycin (mTOR) and Erk-mitogen-activated protein kinase (MAPK) signalings in cultured osteoblasts, which were blocked by EGFR inhibitor AG1478 or monoclonal antibody against EGFR (anti-EGFR). Further, in primary and MC3T3-E1 osteoblasts, epiregulin promoted cell proliferation and increased alkaline phosphatase activity, while inhibiting dexamethasone (Dex)-induced cell death. Such effects by epiregulin were largely inhibited by AG1478 or anti-EGFR. Notably, AKT-mTOR inhibitors, but not Erk inhibitors, alleviated epiregulin-induced above pleiotropic functions in osteoblasts. Meanwhile, siRNA depletion of Sin1, a key component of mTOR complex 2 (mTORC2), also suppressed epiregulin-exerted effects in MC3T3-E1 cells. Together, these results suggest that epiregulin-induced pleiotropic functions in cultured osteoblasts are mediated through EGFR-AKT-mTOR signalings.

  16. High fat fed heart failure animals have enhanced mitochondrial function and acyl-coa dehydrogenase activities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have previously shown that administration of high fat in heart failure (HF) increased mitochondrial respiration and did not alter left ventricular (LV) function. PPARalpha is a nuclear transcription factor that activates expression of genes involved in fatty acid uptake and utilization. We hypoth...

  17. NEUROBEHAVIORAL DATA INTERPRETATION IN NEUROTOXICITY STUDIES: FOB, MOTOR ACTIVITY AND FUNCTION

    EPA Science Inventory

    Neurobehavioral evaluations are emerging as a key component in neurotoxicity testing. The tests most often used for screening are the functional observational battery (FOB) and motor activity. The FOB is a series of non-invasive observational and manipulative measures which ass...

  18. Enhancing activity and stability of Burkholderia cepacia lipase by immobilization on surface-functionalized mesoporous silicates.

    PubMed

    Kato, Katsuya; Seelan, Sindhu

    2010-06-01

    Burkholderia cepacia lipase was immobilized on various types of phenyl-functionalized mesoporous silicates (MPS). MPS, anchored with a phenyl group on the silica wall and with three dimensional (3D) mesoporosity, showed highest lipase adsorption capacity and best activities both in aqueous and organic reagents.

  19. Physical activity in prefrail older adults: confidence and satisfaction related to physical function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We examined the hypothesis that physical activity will have favorable effects on measures of self-efficacy for a 400-m walk and satisfaction with physical functioning in older adults 701 years of age who have deficits in mobility. We randomized a total of 412 adults aged 70–89 years at elevated risk...

  20. A Double-Blind Atropine Trial for Active Learning of Autonomic Function

    ERIC Educational Resources Information Center

    Fry, Jeffrey R.; Burr, Steven A.

    2011-01-01

    Here, we describe a human physiology laboratory class measuring changes in autonomic function over time in response to atropine. Students use themselves as subjects, generating ownership and self-interest in the learning as well as directly experiencing the active link between physiology and pharmacology in people. The class is designed to…

  1. Description of Functional Disability among Younger Stroke Patients: Exploration of Activity and Participation and Environmental Factors

    ERIC Educational Resources Information Center

    Snogren, Maria; Sunnerhagen, Katharina Stibrant

    2009-01-01

    The aim of the study is to describe disability among younger stroke patients by analyzing activity and participation and the environmental aspect as well as to compare assessed and self-perceived problems after stroke. International Classification of Functioning and Health (ICF) is a tool that provides a scientific basis for understanding and…

  2. A Functional Analysis of Moderate-to-Vigorous Physical Activity in Young Children

    ERIC Educational Resources Information Center

    Larson, Tracy A.; Normand, Matthew P.; Morley, Allison J.; Miller, Bryon G.

    2013-01-01

    Inadequate physical activity increases the risks related to a number of health problems in children, most notably obesity and the corresponding range of associated health problems. The purpose of the current study was to conduct a functional analysis to investigate the effects of several consequent variables on moderate-to-vigorous physical…

  3. Functional Brain Activation Differences in Stuttering Identified with a Rapid fMRI Sequence

    ERIC Educational Resources Information Center

    Loucks, Torrey; Kraft, Shelly Jo; Choo, Ai Leen; Sharma, Harish; Ambrose, Nicoline G.

    2011-01-01

    The purpose of this study was to investigate whether brain activity related to the presence of stuttering can be identified with rapid functional MRI (fMRI) sequences that involved overt and covert speech processing tasks. The long-term goal is to develop sensitive fMRI approaches with developmentally appropriate tasks to identify deviant speech…

  4. A Goal Activation Approach to the Study of Executive Function: An Application to Antisaccade Tasks

    ERIC Educational Resources Information Center

    Nieuwenhuis, Sander; Broerse, Annelies; Nielen, Marjan M. A.; de Jong, Ritske

    2004-01-01

    We argue that a general control process, responsible for the activation and maintenance of task goals, is central to the concept of executive function. Failures of this process can become manifest as "goal neglect": disregard of a task requirement even though it has been understood (Duncan, 1995). We discuss the results of several published and…

  5. The function of the earth observing system - Data information system Distributed Active Archive Centers

    NASA Technical Reports Server (NTRS)

    Lapenta, C. C.

    1992-01-01

    The functionality of the Distributed Active Archive Centers (DAACs) which are significant elements of the Earth Observing System Data and Information System (EOSDIS) is discussed. Each DAAC encompasses the information management system, the data archival and distribution system, and the product generation system. The EOSDIS DAACs are expected to improve the access to earth science data set needed for global change research.

  6. The activating transcription factor 3 protein suppresses the oncogenic function of mutant p53 proteins.

    PubMed

    Wei, Saisai; Wang, Hongbo; Lu, Chunwan; Malmut, Sarah; Zhang, Jianqiao; Ren, Shumei; Yu, Guohua; Wang, Wei; Tang, Dale D; Yan, Chunhong

    2014-03-28

    Mutant p53 proteins (mutp53) often acquire oncogenic activities, conferring drug resistance and/or promoting cancer cell migration and invasion. Although it has been well established that such a gain of function is mainly achieved through interaction with transcriptional regulators, thereby modulating cancer-associated gene expression, how the mutp53 function is regulated remains elusive. Here we report that activating transcription factor 3 (ATF3) bound common mutp53 (e.g. R175H and R273H) and, subsequently, suppressed their oncogenic activities. ATF3 repressed mutp53-induced NFKB2 expression and sensitized R175H-expressing cancer cells to cisplatin and etoposide treatments. Moreover, ATF3 appeared to suppress R175H- and R273H-mediated cancer cell migration and invasion as a consequence of preventing the transcription factor p63 from inactivation by mutp53. Accordingly, ATF3 promoted the expression of the metastasis suppressor SHARP1 in mutp53-expressing cells. An ATF3 mutant devoid of the mutp53-binding domain failed to disrupt the mutp53-p63 binding and, thus, lost the activity to suppress mutp53-mediated migration, suggesting that ATF3 binds to mutp53 to suppress its oncogenic function. In line with these results, we found that down-regulation of ATF3 expression correlated with lymph node metastasis in TP53-mutated human lung cancer. We conclude that ATF3 can suppress mutp53 oncogenic function, thereby contributing to tumor suppression in TP53-mutated cancer.

  7. Poor Vision, Functioning, and Depressive Symptoms: A Test of the Activity Restriction Model

    ERIC Educational Resources Information Center

    Bookwala, Jamila; Lawson, Brendan

    2011-01-01

    Purpose: This study tested the applicability of the activity restriction model of depressed affect to the context of poor vision in late life. This model hypothesizes that late-life stressors contribute to poorer mental health not only directly but also indirectly by restricting routine everyday functioning. Method: We used data from a national…

  8. Employment Activities and Experiences of Adults with High-Functioning Autism and Asperger's Disorder

    ERIC Educational Resources Information Center

    Baldwin, Susanna; Costley, Debra; Warren, Anthony

    2014-01-01

    There is limited large-scale empirical research into the working lives of adults who have an autism spectrum disorder with no co-occurring intellectual disability. Drawing on data from a national survey, this report describes the employment activities and experiences of 130 adults with Asperger's Disorder (AD) and high functioning autism (HFA) in…

  9. Importance of being Nernst: Synaptic activity and functional relevance in stem cell-derived neurons

    PubMed Central

    Bradford, Aaron B; McNutt, Patrick M

    2015-01-01

    Functional synaptogenesis and network emergence are signature endpoints of neurogenesis. These behaviors provide higher-order confirmation that biochemical and cellular processes necessary for neurotransmitter release, post-synaptic detection and network propagation of neuronal activity have been properly expressed and coordinated among cells. The development of synaptic neurotransmission can therefore be considered a defining property of neurons. Although dissociated primary neuron cultures readily form functioning synapses and network behaviors in vitro, continuously cultured neurogenic cell lines have historically failed to meet these criteria. Therefore, in vitro-derived neuron models that develop synaptic transmission are critically needed for a wide array of studies, including molecular neuroscience, developmental neurogenesis, disease research and neurotoxicology. Over the last decade, neurons derived from various stem cell lines have shown varying ability to develop into functionally mature neurons. In this review, we will discuss the neurogenic potential of various stem cells populations, addressing strengths and weaknesses of each, with particular attention to the emergence of functional behaviors. We will propose methods to functionally characterize new stem cell-derived neuron (SCN) platforms to improve their reliability as physiological relevant models. Finally, we will review how synaptically active SCNs can be applied to accelerate research in a variety of areas. Ultimately, emphasizing the critical importance of synaptic activity and network responses as a marker of neuronal maturation is anticipated to result in in vitro findings that better translate to efficacious clinical treatments. PMID:26240679

  10. Coevolution between human's anticancer activities and functional foods from crop origin center in the world.

    PubMed

    Zeng, Ya-Wen; Du, Juan; Pu, Xiao-Ying; Yang, Jia-Zhen; Yang, Tao; Yang, Shu-Ming; Yang, Xiao-Meng

    2015-01-01

    Cancer is the leading cause of death around the world. Anticancer activities from many functional food sources have been reported in years, but correlation between cancer prevalence and types of food with anticancer activities from crop origin center in the world as well as food source with human migration are unclear. Hunger from food shortage is the cause of early human evolution from Africa to Asia and later into Eurasia. The richest functional foods are found in crop origin centers, housing about 70% in the world populations. Crop origin centers have lower cancer incidence and mortality in the world, especially Central Asia, Middle East, Southwest China, India and Ethiopia. Asia and Africa with the richest anticancer crops is not only the most important evolution base of humans and origin center of anticancer functional crop, but also is the lowest mortality and incidence of cancers in the world. Cancer prevention of early human migrations was associated with functional foods from crop origin centers, especially Asia with four centers and one subcenter of crop origin, accounting for 58% of the world population. These results reveal that coevolution between human's anticancer activities associated with functional foods for crop origin centers, especially in Asia and Africa.

  11. Disconnect of microbial structure and function: enzyme activities and bacterial communities in nascent stream corridors

    PubMed Central

    Frossard, Aline; Gerull, Linda; Mutz, Michael; Gessner, Mark O

    2012-01-01

    A fundamental issue in microbial and general ecology is the question to what extent environmental conditions dictate the structure of communities and the linkages with functional properties of ecosystems (that is, ecosystem function). We approached this question by taking advantage of environmental gradients established in soil and sediments of small stream corridors in a recently created, early successional catchment. Specifically, we determined spatial and temporal patterns of bacterial community structure and their linkages with potential microbial enzyme activities along the hydrological flow paths of the catchment. Soil and sediments were sampled in a total of 15 sites on four occasions spread throughout a year. Denaturing gradient gel electrophoresis (DGGE) was used to characterize bacterial communities, and substrate analogs linked to fluorescent molecules served to track 10 different enzymes as specific measures of ecosystem function. Potential enzyme activities varied little among sites, despite contrasting environmental conditions, especially in terms of water availability. Temporal changes, in contrast, were pronounced and remarkably variable among the enzymes tested. This suggests much greater importance of temporal dynamics than spatial heterogeneity in affecting specific ecosystem functions. Most strikingly, bacterial community structure revealed neither temporal nor spatial patterns. The resulting disconnect between bacterial community structure and potential enzyme activities indicates high functional redundancy within microbial communities even in the physically and biologically simplified stream corridors of early successional landscapes. PMID:22030674

  12. Physical activity play: the nature and function of a neglected aspect of playing.

    PubMed

    Pellegrini, A D; Smith, P K

    1998-06-01

    In this review, we consider the nature and possible developmental functions of physical activity play, defined as a playful context combined with a dimension of physical vigor. We distinguish 3 kinds of physical activity play, with consecutive age peaks: rhythmic stereotypies peaking in infancy, exercise play peaking during the preschool years, and rough-and-tumble play peaking in middle childhood. Gender differences (greater prevalence in males) characterize the latter 2 forms. Function is considered in terms of beneficial immediate and deferred consequences in physical, cognitive, and social domains. Whereas most theories assume that children's play has deferred benefits, we suggest that forms of physical activity play serve primarily immediate developmental functions. Rhythmic stereotypies in infancy are hypothesized to improve control of specific motor patterns. Exercise play is hypothesized to function primarily for strength and endurance training; less clear evidence exists for possible benefits for fat reduction and thermoregulation. In addition, there may be cognitive benefits of exercise play that we hypothesize to be largely incidental to its playful or physical nature. Rough-and-tumble play has a distinctive social component; we hypothesize that it serves primarily dominance functions; evidence for benefits to fighting skills or to emotional coding are more equivocal. Further research is indicated, given the potentially important implications for children's education, health, and development.

  13. Functional response and population dynamics for fighting predator, based on activity distribution.

    PubMed

    Garay, József; Varga, Zoltán; Gámez, Manuel; Cabello, Tomás

    2015-03-07

    The classical Holling type II functional response, describing the per capita predation as a function of prey density, was modified by Beddington and de Angelis to include interference of predators that increases with predator density and decreases the number of killed prey. In the present paper we further generalize the Beddington-de Angelis functional response, considering that all predator activities (searching and handling prey, fight and recovery) have time duration, the probabilities of predator activities depend on the encounter probabilities, and hence on the prey and predator abundance, too. Under these conditions, the aim of the study is to introduce a functional response for fighting the predator and to analyse the corresponding dynamics, when predator-predator-prey encounters also occur. From this general approach, the Holling type functional responses can also be obtained as particular cases. In terms of the activity distribution, we give biologically interpretable sufficient conditions for stable coexistence. We consider two-individual (predator-prey) and three-individual (predator-predator-prey) encounters. In the three-individual encounter model there is a relatively higher fighting rate and a lower killing rate. Using numerical simulation, we surprisingly found that when the intrinsic prey growth rate and the conversion rate are small enough, the equilibrium predator abundance is higher in the three-individual encounter case. The above means that, when the equilibrium abundance of the predator is small, coexistence appears first in the three-individual encounter model.

  14. Functional relationships between the masseter and sternocleidomastoid muscle activities during gum chewing:.

    PubMed

    Shimazaki, Kazuo; Matsubara, Nozomu; Hisano, Masataka; Soma, Kunimichi

    2006-05-01

    The purpose of this study was to investigate the functional relationship between masseter muscle (MM) and sternocleidomastoid muscle (SCM) activities and between mandibular and head movements during mastication, under experimental muscle fatigue. The sample consisted of 12 adults with individually normal occlusion. The subjects were asked to chew gum at three different times: before maximum clenching, immediately after maximum clenching, and 3 minutes after maximum clenching. At these times, we examined the activity of the MM and SCM as well as the movement of the mandible and head. The activity and movement were simultaneously measured using both electromyography and the motion capture system. The MM activity time after clenching was significantly shorter than that before clenching, whereas the SCM activity time was significantly longer after clenching. There was no significant difference in the changes of three-dimensional distance of the mandibular movement between the respective times. On the other hand, the changes in the three-dimensional distance of head movement after clenching increased when compared with before clenching. Furthermore, the difference in the time of MM and SCM activity onset and of mandibular and head movement onset after clenching was shorter than that before clenching. A functional relationship exists between the MM and SCM activities and between mandibular and head movements during mastication.

  15. PERK activation preserves the viability and function of remyelinating oligodendrocytes in immune-mediated demyelinating diseases.

    PubMed

    Lin, Yifeng; Huang, Guangcun; Jamison, Stephanie; Li, Jin; Harding, Heather P; Ron, David; Lin, Wensheng

    2014-02-01

    Remyelination occurs in multiple sclerosis (MS) lesions but is generally considered to be insufficient. One of the major challenges in MS research is to understand the causes of remyelination failure and to identify therapeutic targets that promote remyelination. Activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum stress modulates cell viability and function under stressful conditions. There is evidence that PERK is activated in remyelinating oligodendrocytes in demyelinated lesions in both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). In this study, we sought to determine the role of PERK signaling in remyelinating oligodendrocytes in MS and EAE using transgenic mice that allow temporally controlled activation of PERK signaling specifically in oligodendrocytes. We demonstrated that persistent PERK activation was not deleterious to myelinating oligodendrocytes in young, developing mice or to remyelinating oligodendrocytes in cuprizone-induced demyelinated lesions. We found that enhancing PERK activation, specifically in (re)myelinating oligodendrocytes, protected the cells and myelin against the detrimental effects of interferon-γ, a key proinflammatory cytokine in MS and EAE. More important, we showed that enhancing PERK activation in remyelinating oligodendrocytes at the recovery stage of EAE promoted cell survival and remyelination in EAE demyelinated lesions. Thus, our data provide direct evidence that PERK activation cell-autonomously enhances the survival and preserves function of remyelinating oligodendrocytes in immune-mediated demyelinating diseases.

  16. Multistability of complex-valued neural networks with discontinuous activation functions.

    PubMed

    Liang, Jinling; Gong, Weiqiang; Huang, Tingwen

    2016-12-01

    In this paper, based on the geometrical properties of the discontinuous activation functions and the Brouwer's fixed point theory, the multistability issue is tackled for the complex-valued neural networks with discontinuous activation functions and time-varying delays. To address the network with discontinuous functions, Filippov solution of the system is defined. Through rigorous analysis, several sufficient criteria are obtained to assure the existence of 25(n) equilibrium points. Among them, 9(n) points are locally stable and 16(n)-9(n) equilibrium points are unstable. Furthermore, to enlarge the attraction basins of the 9(n) equilibrium points, some mild conditions are imposed. Finally, one numerical example is provided to illustrate the effectiveness of the obtained results.

  17. Absolute exponential stability of recurrent neural networks with Lipschitz-continuous activation functions and time delays.

    PubMed

    Cao, Jinde; Wang, Jun

    2004-04-01

    This paper investigates the absolute exponential stability of a general class of delayed neural networks, which require the activation functions to be partially Lipschitz continuous and monotone nondecreasing only, but not necessarily differentiable or bounded. Three new sufficient conditions are derived to ascertain whether or not the equilibrium points of the delayed neural networks with additively diagonally stable interconnection matrices are absolutely exponentially stable by using delay Halanay-type inequality and Lyapunov function. The stability criteria are also suitable for delayed optimization neural networks and delayed cellular neural networks whose activation functions are often nondifferentiable or unbounded. The results herein answer a question: if a neural network without any delay is absolutely exponentially stable, then under what additional conditions, the neural networks with delay is also absolutely exponentially stable.

  18. Synthesis of polyethylenimine (PEI) functionalized silver nanoparticles by a hydrothermal method and their antibacterial activity study.

    PubMed

    Liu, Zhiguo; Wang, Yuanlin; Zu, Yuangang; Fu, Yujie; Li, Na; Guo, Na; Liu, Ruisi; Zhang, Yiming

    2014-09-01

    In this study, we report a facile, one-step hydrothermal method to synthesize PEI-functionalized Ag nanoparticles in which no extra reducing agent is needed and PEI serves as a reducing agent and a stabilizing agent. The obtained Ag colloids have been characterized by TEM, UV absorption spectra and laser particle size analyzer. We found that the size of Ag nanoparticles can be tuned through the alteration of the temperature and growth mode. Under an acidic condition, PEI-functionalized Ag nanoparticles are positively charged. More importantly, the Ag colloids exhibited stronger antibacterial activity in the bactericidal test. Its bactericidal efficiency exceeds the commonly used antibacterial agents such as Erythromycin, chloramphenicol and penicillin as well as AgNO3 solution. These results prove that our synthesis method is very efficient to produce a stable PEI-functionalized Ag colloid with excellent antibacterial activity.

  19. The memory function of noradrenergic activity in non-REM sleep.

    PubMed

    Gais, Steffen; Rasch, Björn; Dahmen, Johannes C; Sara, Susan; Born, Jan

    2011-09-01

    There is a long-standing assumption that low noradrenergic activity during sleep reflects mainly the low arousal during this brain state. Nevertheless, recent research has demonstrated that the locus coeruleus, which is the main source of cortical noradrenaline, displays discrete periods of intense firing during non-REM sleep, without any signs of awakening. This transient locus coeruleus activation during sleep seems to occur in response to preceding learning-related episodes. In the present study, we manipulate noradrenergic activity during sleep in humans with either the α2-autoreceptor agonist clonidine or the noradrenaline reuptake inhibitor reboxetine. We show that reducing noradrenergic activity during sleep, but not during wakefulness, impairs subsequent memory performance in an odor recognition task. Increasing noradrenergic availability during sleep, in contrast, enhances memory retention. We conclude that noradrenergic activity during non-REM sleep interacts with other sleep-related mechanisms to functionally contribute to off-line memory consolidation.

  20. New insights into the activation, interaction partners and possible functions of MK5/PRAK.

    PubMed

    Perander, Maria; Keyse, Stephen M; Seternes, Ole-Morten

    2016-01-01

    MAP kinase-activated protein kinase 5 (MK5) was first described as a downstream target of the p38 MAP kinase pathway leading to its alternative acronym of p38-regulated/activated protein kinase (PRAK). However, since the discovery that MK5 is a bona fide interaction partner of the atypical MAP kinases ERK3 and ERK4 and that this interaction leads to both the activation and subcellular relocalisation of MK5, there has been considerable debate as to the relative roles of these MAPK pathways in mediating the activation and biological functions of MK5. Here we discuss recent progress in defining novel upstream components of the ERK3/ERK4 signalling pathway, our increased understanding of the mechanism by which MK5 interacts with and is activated by ERK3 and ERK4, and the discovery of novel interaction partners for MK5. Finally, we review recent literature that suggests novel biological functions for MK5 in a range of physiological and pathophysiological conditions including neuronal function and cancer.

  1. Altered resting-state functional activity in posttraumatic stress disorder: A quantitative meta-analysis

    PubMed Central

    Wang, Ting; Liu, Jia; Zhang, Junran; Zhan, Wang; Li, Lei; Wu, Min; Huang, Hua; Zhu, Hongyan; Kemp, Graham J.; Gong, Qiyong

    2016-01-01

    Many functional neuroimaging studies have reported differential patterns of spontaneous brain activity in posttraumatic stress disorder (PTSD), but the findings are inconsistent and have not so far been quantitatively reviewed. The present study set out to determine consistent, specific regional brain activity alterations in PTSD, using the Effect Size Signed Differential Mapping technique to conduct a quantitative meta-analysis of resting-state functional neuroimaging studies of PTSD that used either a non-trauma (NTC) or a trauma-exposed (TEC) comparison control group. Fifteen functional neuroimaging studies were included, comparing 286 PTSDs, 203 TECs and 155 NTCs. Compared with NTC, PTSD patients showed hyperactivity in the right anterior insula and bilateral cerebellum, and hypoactivity in the dorsal medial prefrontal cortex (mPFC); compared with TEC, PTSD showed hyperactivity in the ventral mPFC. The pooled meta-analysis showed hypoactivity in the posterior insula, superior temporal, and Heschl’s gyrus in PTSD. Additionally, subgroup meta-analysis (non-medicated subjects vs. NTC) identified abnormal activation in the prefrontal-limbic system. In meta-regression analyses, mean illness duration was positively associated with activity in the right cerebellum (PTSD vs. NTC), and illness severity was negatively associated with activity in the right lingual gyrus (PTSD vs. TEC). PMID:27251865

  2. Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3

    PubMed Central

    Kang, Seokwon; Fernandes-Alnemri, Teresa; Rogers, Corey; Mayes, Lindsey; Wang, Ying; Dillon, Christopher; Roback, Linda; Kaiser, William; Oberst, Andrew; Sagara, Junji; Fitzgerald, Katherine A.; Green, Douglas R.; Zhang, Jianke; Mocarski, Edward S.; Alnemri, Emad S.

    2015-01-01

    TLR2 promotes NLRP3 inflammasome activation via an early MyD88-IRAK1-dependent pathway that provides a priming signal (signal 1) necessary for activation of the inflammasome by a second potassium-depleting signal (signal 2). Here we show that TLR3 binding to dsRNA promotes post-translational inflammasome activation through intermediate and late TRIF/RIPK1/FADD-dependent pathways. Both pathways require the scaffolding but not the catalytic function of caspase-8 or RIPK1. Only the late pathway requires kinase competent RIPK3 and MLKL function. Mechanistically, FADD/caspase-8 scaffolding function provides a post-translational signal 1 in the intermediate pathway, whereas in the late pathway it helps the oligomerization of RIPK3, which together with MLKL provides both signal 1 and 2 for inflammasome assembly. Cytoplasmic dsRNA activates NLRP3 independent of TRIF, RIPK1, RIPK3 or mitochondrial DRP1, but requires FADD/caspase-8 in wildtype macrophages to remove RIPK3 inhibition. Our study provides a comprehensive analysis of pathways that lead to NLRP3 inflammasome activation in response to dsRNA. PMID:26104484

  3. Joint maximum likelihood estimation of activation and Hemodynamic Response Function for fMRI.

    PubMed

    Bazargani, Negar; Nosratinia, Aria

    2014-07-01

    Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) maps the brain activity by measuring blood oxygenation level, which is related to brain activity via a temporal impulse response function known as the Hemodynamic Response Function (HRF). The HRF varies from subject to subject and within areas of the brain, therefore a knowledge of HRF is necessary for accurately computing voxel activations. Conversely a knowledge of active voxels is highly beneficial for estimating the HRF. This work presents a joint maximum likelihood estimation of HRF and activation based on low-rank matrix approximations operating on regions of interest (ROI). Since each ROI has limited data, a smoothing constraint on the HRF is employed via Tikhonov regularization. The method is analyzed under both white noise and colored noise. Experiments with synthetic data show that accurate estimation of the HRF is possible with this method without prior assumptions on the exact shape of the HRF. Further experiments involving real fMRI experiments with auditory stimuli are used to validate the proposed method.

  4. Activation detection in functional near-infrared spectroscopy by wavelet coherence

    NASA Astrophysics Data System (ADS)

    Zhang, Xin; Yu, Jian; Zhao, Ruirui; Xu, Wenting; Niu, Haijing; Zhang, Yujin; Zuo, Nianming; Jiang, Tianzi

    2015-01-01

    Functional near-infrared spectroscopy (fNIRS) detects hemodynamic responses in the cerebral cortex by transcranial spectroscopy. However, measurements recorded by fNIRS not only consist of the desired hemodynamic response but also consist of a number of physiological noises. Because of these noises, accurately detecting the regions that have an activated hemodynamic response while performing a task is a challenge when analyzing functional activity by fNIRS. In order to better detect the activation, we designed a multiscale analysis based on wavelet coherence. In this method, the experimental paradigm was expressed as a binary signal obtained while either performing or not performing a task. We convolved the signal with the canonical hemodynamic response function to predict a possible response. The wavelet coherence was used to investigate the relationship between the response and the data obtained by fNIRS at each channel. Subsequently, the coherence within a region of interest in the time-frequency domain was summed to evaluate the activation level at each channel. Experiments on both simulated and experimental data demonstrated that the method was effective for detecting activated channels hidden in fNIRS data.

  5. Neuroanatomic substrates of semantic memory impairment in Alzheimer’s disease: Patterns of functional MRI activation

    PubMed Central

    SAYKIN, ANDREW J.; FLASHMAN, LAURA A.; FRUTIGER, SALLY A.; JOHNSON, STERLING C.; MAMOURIAN, ALEXANDER C.; MORITZ, CHAD H.; O’JILE, JUDITH R.; RIORDAN, HENRY J.; SANTULLI, ROBERT B.; SMITH, CYNTHIA A.; WEAVER, JOHN B.

    2015-01-01

    Impairment in semantic processing occurs early in Alzheimer’s disease (AD) and differential impact on subtypes of semantic relations have been reported, yet there is little data on the neuroanatomic basis of these deficits. Patients with mild AD and healthy controls underwent 3 functional MRI auditory stimulation tasks requiring semantic or phonological decisions (match–mismatch) about word pairs (category–exemplar, category–function, pseudoword). Patients showed a significant performance deficit only on the exemplar task. On voxel-based fMRI activation analyses, controls showed a clear activation focus in the left superior temporal gyrus for the phonological task; patients showed additional foci in the left dorsolateral prefrontal and bilateral cingulate areas. On the semantic tasks, predominant activation foci were seen in the inferior and middle frontal gyrus (left greater than right) in both groups but patients showed additional activation suggesting compensatory recruitment of locally expanded foci and remote regions, for example, right frontal activation during the exemplar task. Covariance analyses indicated that exemplar task performance was strongly related to signal increase in bilateral medial prefrontal cortex. The authors conclude that fMRI can reveal similarities and differences in functional neuroanatomical processing of semantic and phonological information in mild AD compared to healthy elderly, and can help to bridge cognitive and neural investigations of the integrity of semantic networks in AD. PMID:10439584

  6. Functional activation and neural networks in women with posttraumatic stress disorder related to intimate partner violence

    PubMed Central

    Simmons, Alan; Paulus, Martin P.; Thorp, Steven R.; Matthews, Scott C.; Norman, Sonya B.; Stein, Murray B.

    2008-01-01

    Background Intimate partner violence (IPV) is one of the most common causes of posttraumatic stress disorder (PTSD) in women. Victims of IPV are often preoccupied by the anticipation of impending harm. This investigation tested the hypothesis that IPV-related PTSD individuals show exaggerated insula reactivity to the anticipation of aversive stimuli. Methods Fifteen women with a history of IPV and consequent PTSD (IPV-PTSD) and 15 non-traumatized control (NTC) women performed a task involving cued anticipation to images of positive and negative events during functional magnetic resonance imaging. Results Both groups showed increased activation of bilateral anterior insula during anticipation of negative images minus anticipation of positive images. Activation in right anterior/middle insula was significantly greater in the IPV-PTSD relative to the NTC group. Functional connectivity analysis revealed that changes in activation in right middle insula and bilateral anterior insula were more strongly associated with amygdala activation changes in NTC than in IPV-PTSD subjects. Conclusions Increased activation in the anterior/middle insula during negative anticipation in women with IPV-related PTSD. These findings in women with IPV could be a consequence of the IPV exposure, reflect pre-existing differences in insular function, or due to the development of PTSD. Thus, future longitudinal studi4s need to examine these possibilities. PMID:18639236

  7. Activation of Melatonin Signaling Promotes β-Cell Survival and Function.

    PubMed

    Costes, Safia; Boss, Marti; Thomas, Anthony P; Matveyenko, Aleksey V

    2015-05-01

    Type 2 diabetes mellitus (T2DM) is characterized by pancreatic islet failure due to loss of β-cell secretory function and mass. Studies have identified a link between a variance in the gene encoding melatonin (MT) receptor 2, T2DM, and impaired insulin secretion. This genetic linkage raises the question whether MT signaling plays a role in regulation of β-cell function and survival in T2DM. To address this postulate, we used INS 832/13 cells to test whether activation of MT signaling attenuates proteotoxicity-induced β-cell apoptosis and through which molecular mechanism. We also used nondiabetic and T2DM human islets to test the potential of MT signaling to attenuate deleterious effects of glucotoxicity and T2DM on β-cell function. MT signaling in β-cells (with duration designed to mimic typical nightly exposure) significantly enhanced activation of the cAMP-dependent signal transduction pathway and attenuated proteotoxicity-induced β-cell apoptosis evidenced by reduced caspase-3 cleavage (∼40%), decreased activation of stress-activated protein kinase/Jun-amino-terminal kinase (∼50%) and diminished oxidative stress response. Activation of MT signaling in human islets was shown to restore glucose-stimulated insulin secretion in islets exposed to chronic hyperglycemia as well as in T2DM islets. Our data suggest that β-cell MT signaling is important for the regulation of β-cell survival and function and implies a preventative and therapeutic potential for preservation of β-cell mass and function in T2DM.

  8. Involvement of Hevea latex organelle membrane proteins in the rubber biosynthesis activity and regulatory function.

    PubMed

    Wititsuwaannakul, Dhirayos; Rattanapittayaporn, Atiya; Koyama, Tanetoshi; Wititsuwaannakul, Rapepun

    2004-03-15

    Centrifugation of fresh Hevea rubber latex yields three distinct fractions. The sediment bottom fraction (BF) content of membrane-bound organelles is ca. 20 vol.-% of latex. Prolonged storage or delayed use of fresh latex will result in disintegration and loss of the bottom fraction. This is due to the osmotically sensitive BF rupture and its membrane debris being tightly bound to the top rubber particles (RP) phase. The BF membrane was found to be highly active for rubber biosynthesis (RB), in contrast to previous reports that describe RB only occurring on the RP surface. It was clearly shown that washed BF membrane (WBM) was much more active than fresh RP for RB activity. WBM was highly activated by SDS for RB in a biphasic manner, but SDS strongly inhibited the RP. Probably WBM micelle formation resulted in a highly increased active surface area for RB. C55-PP (UPP) was a very active allylic for WBM in RB function, but inactive for RP. Serial acetone extraction of WBM proteins showed a distinct profile of the fractions with different RB activity. WBM isolated proteins suspended in 2% sodium dodecyl sulfate (SDS) with an RB activity equal to that of intact WBM was with the 20% acetone protein fraction. The 60 and 80% fractions were inactive. Combining the 20 with 80% fractions showed a complete inhibition of RB activity. Complete RB loss was also found when WBM was mixed with the 80% fraction, indicating that WBM has both an enzyme system and a factor for regulation of the RB activity in a well controlled metabolic function for the latex RB process.

  9. Patterns of Spontaneous Local Network Activity in Developing Cerebral Cortex: Relationship to Adult Cognitive Function.

    PubMed

    Peinado, Alejandro; Abrams, Charles K

    2015-01-01

    Detecting neurodevelopμental disorders of cognition at the earliest possible stages could assist in understanding them mechanistically and ultimately in treating them. Finding early physiological predictors that could be visualized with functional neuroimaging would represent an important advance in this regard. We hypothesized that one potential source of physiological predictors is the spontaneous local network activity prominent during specific periods in development. To test this we used calcium imaging in brain slices and analyzed variations in the frequency and intensity of this early activity in one area, the entorhinal cortex (EC), in order to correlate early activity with level of cognitive function later in life. We focused on EC because of its known role in different types of cognitive processes and because it is an area where spontaneous activity is prominent during early postnatal development in rodent models of cortical development. Using rat strains (Long-Evans, Wistar, Sprague-Dawley and Brattleboro) known to differ in cognitive performance in adulthood we asked whether neonatal animals exhibit corresponding strain-related differences in EC spontaneous activity. Our results show significant differences in this activity between strains: compared to a high cognitive-performing strain, we consistently found an increase in frequency and decrease in intensity in neonates from three lower performing strains. Activity was most different in one strain considered a model of schizophrenia-like psychopathology. While we cannot necessarily infer a causal relationship between early activity and adult cognition our findings suggest that the pattern of spontaneous activity in development could be an early predictor of a developmental trajectory advancing toward sub-optimal cognitive performance in adulthood. Our results further suggest that the strength of dopaminergic signaling, by setting the balance between excitation and inhibition, is a potential underlying

  10. High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes.

    PubMed

    Hidalgo, Marta R; Cubuk, Cankut; Amadoz, Alicia; Salavert, Francisco; Carbonell-Caballero, José; Dopazo, Joaquin

    2017-01-17

    Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is a main challenge for precision medicine. Here we propose a new method that models cell signaling using biological knowledge on signal transduction. The method recodes individual gene expression values (and/or gene mutations) into accurate measurements of changes in the activity of signaling circuits, which ultimately constitute high-throughput estimations of cell functionalities caused by gene activity within the pathway. Moreover, such estimations can be obtained either at cohort-level, in case/control comparisons, or personalized for individual patients. The accuracy of the method is demonstrated in an extensive analysis involving 5640 patients from 12 different cancer types. Circuit activity measurements not only have a high diagnostic value but also can be related to relevant disease outcomes such as survival, and can be used to assess therapeutic interventions.

  11. [Active alveolar expansion for prevention of postoperative atelectasis. Functional and clinical effectiveness].

    PubMed

    Adolf, J; Dickmann, A

    1985-12-13

    In a prospective study, the functional and clinical effectiveness of active alveolar expansion was tested by means of an incentive spirometer on 30 patients each of a treatment and control group. All patients (average age 61 and 58 years, respectively) had undergone a transabdominal pelvic artery reconstruction. Pre-operatively active alveolar expansion significantly reduced intrapulmonary right to left shunting from 11.1% to 4.2% of cardiac output (P less than 0.01). Correspondingly, right to left shunting on the second to fifth postoperative day was reduced significantly (P less than 0.05) by 5-10% of cardiac output in the treatment group, cardiac output being significantly (P less than 0.05) reduced by 1 l/min average. Clinically and radiologically there was a definite reduction in pulmonary complications from 40% to 13%. Peri-operatively performed active alveolar expansion is thus an effective method for the reduction of postoperative functional atelectasis and pulmonary complications.

  12. Calcineurin functions in Ca(2+)-activated cell death in mammalian cells

    PubMed Central

    1995-01-01

    Calcineurin is a calcium-dependent protein phosphatase that functions in T cell activation. We present evidence that calcineurin functions more generally in calcium-triggered apoptosis in mammalian cells deprived of growth factors. Specifically, expression of epitope-tagged calcineurin A induces rapid cell death upon calcium signaling in the absence of growth factors. We show that this apoptosis does not require new protein synthesis and therefore calcineurin must operate through existing substrates. Co-expression of the Bcl-2 protooncogene efficiently blocks calcineurin-induced cell death. Significantly, we demonstrate that a calcium-independent calcineurin mutant induces apoptosis in the absence of calcium, and that this apoptotic response is a direct consequence of calcineurin's phosphatase activity. These data suggest that calcineurin plays an important role in mediating the upstream events in calcium-activated cell death. PMID:7593193

  13. Disassociation between brain activation and executive function in fragile X premutation females.

    PubMed

    Shelton, Annie L; Cornish, Kim; Clough, Meaghan; Gajamange, Sanuji; Kolbe, Scott; Fielding, Joanne

    2017-02-01

    Executive dysfunction has been demonstrated among premutation (PM) carriers (55-199 CGG repeats) of the Fragile X mental retardation 1 (FMR1) gene. Further, alterations to neural activation patterns have been reported during memory and comparison based functional magnetic resonance imaging (fMRI) tasks in these carriers. For the first time, the relationships between fMRI neural activation during an interleaved ocular motor prosaccade/antisaccade paradigm, and concurrent task performance (saccade measures of latency, accuracy and error rate) in PM females were examined. Although no differences were found in whole brain activation patterns, regions of interest (ROI) analyses revealed reduced activation in the right ventrolateral prefrontal cortex (VLPFC) during antisaccade trials for PM females. Further, a series of divergent and group specific relationships were found between ROI activation and saccade measures. Specifically, for control females, activation within the right VLPFC and supramarginal gyrus correlated negatively with antisaccade latencies, while for PM females, activation within these regions was found to negatively correlate with antisaccade accuracy and error rate (right VLPFC only). For control females, activation within frontal and supplementary eye fields and bilateral intraparietal sulci correlated with prosaccade latency and accuracy; however, no significant prosaccade correlations were found for PM females. This exploratory study extends previous reports of altered prefrontal neural engagement in PM carriers, and clearly demonstrates dissociation between control and PM females in the transformation of neural activation into overt measures of executive dysfunction. Hum Brain Mapp 38:1056-1067, 2017. © 2016 Wiley Periodicals, Inc.

  14. Intensity of recreational physical activity throughout life and later life cognitive functioning in women.

    PubMed

    Tierney, Mary C; Moineddin, Rahim; Morra, Angela; Manson, Judith; Blake, Jennifer

    2010-01-01

    Long-term physical activity may affect risk of cognitive impairment but few studies have examined later life cognition in relation to intensity of life-long physical activity. We examined the associations between the intensity of long-term recreational physical activity and neuropsychological functioning in 90 healthy postmenopausal women on tests found to be useful in the early identification of dementia. Information was collected about their participation in strenuous and moderate activities between high school and menopause. Summary measures of long-term strenuous and moderate activity were constructed for each participant. All analyses were adjusted for relevant covariates. The six linear regression analyses showed significant positive associations between moderate activity and Wechsler Adult Intelligence Scale Revised (WAIS-R), Digit Span backward, WAIS-R Digit Symbol, and Trail Making Test Part B. Significant negative relationships were found between strenuous activity and Rey Auditory Verbal Learning Test delayed verbal recall, Complex Figure Test delayed visual memory, WAIS-R Digit Span backward, category fluency, and WAIS-R Digit Symbol. The associations found in the present study suggest that while moderate activity may be protective, long-term strenuous activity before menopause may lower cognitive performance later in life. These results support further investigation of the effects of life-long exercise intensity on cognition in later life.

  15. Sodium channel activation augments NMDA receptor function and promotes neurite outgrowth in immature cerebrocortical neurons

    PubMed Central

    George, Joju; Dravid, Shashank M.; Prakash, Anand; Xie, Jun; Peterson, Jennifer; Jabba, Sairam V.; Baden, Daniel G.; Murray, Thomas F.

    2009-01-01

    A range of extrinsic signals, including afferent activity, affect neuronal growth and plasticity. Neuronal activity regulates intracellular Ca2+ and activity-dependent calcium signaling has been shown to regulate dendritic growth and branching (Konur and Ghosh, 2005). NMDA receptor (NMDAR) stimulation of Ca2+/calmodulin-dependent protein kinase signaling cascades has moreover been demonstrated to regulate neurite/axonal outgrowth (Wayman et al., 2004). We used a sodium channel activator, brevetoxin (PbTx-2), to explore the relationship between intracellular [Na+] and NMDAR-dependent development. PbTx-2 alone, at a concentration of 30 nM, did not affect Ca2+ dynamics in DIV-2 cerebrocortical neurons; however, this treatment robustly potentiated NMDA-induced Ca2+ influx. The 30 nM PbTx-2 treatment produced a maximum [Na+]i of 16.9 ± 1.5 mM representing an increment of 8.8 ± 1.8 mM over basal. The corresponding membrane potential change produced by 30 nM PbTx-2 was modest and therefore insufficient to relieve the voltage-dependent Mg2+ block of NMDARs. To unambiguously demonstrate the enhancement of NMDA receptor function by PbTx-2, we recorded single-channel currents from cell-attached patches. PbTx-2 treatment was found to increase both the mean open time and open probability of NMDA receptors. These effects of PbTx-2 on NMDA receptor function were dependent on extracellular Na+ and activation of Src kinase. The functional consequences of PbTx-2-induced enhancement of NMDAR function were evaluated in immature cerebrocortical neurons. PbTx-2 concentrations between 3 and 300 nM enhanced neurite outgrowth. Voltage-gated sodium channel activators may accordingly represent a novel pharmacologic strategy to regulate neuronal plasticity through an NMDA receptor and Src family kinase-dependent mechanism. PMID:19279266

  16. The Daily Activity Report (DAR) a Novel Measure of Functional Outcome for Serious Mental Illness

    PubMed Central

    Velligan, Dawn I.; Mintz, Jim; Sierra, Cynthia; Martin, Mona L.; Fredrick, Megan; Maglinte, Gregory A.; Corey-Lisle, Patricia K.

    2016-01-01

    The assessment of real-world functional outcomes in clinical trials for medications targeting negative symptoms and cognitive impairment is extremely important. We tested the psychometric properties of the Daily Activity Report (DAR), a novel assessment of productive daily activity. We administered the DAR and additional assessments of functional outcome, functional capacity, cognition and symptomatology to 50 individuals with schizophrenia at 2 time points, 1 month apart and to 25 healthy controls. The DAR records a person’s daily activity for 7 consecutive days based upon phone calls made 3 times a day. A total score and scores in 3 domains; instrumental activities (ie, independent living), social and work or school related activities are generated for the DAR. Inter-item consistency was high 0.89–0.94 for each domain and 0.88 overall. Test–retest reliability across 1 month for the total DAR score was 0.67, P < .0001. The total DAR score as well as scores for social activity and nondomestic work/school differed significantly between control and patient participants (P < .0001). DAR domain scores were associated with negative symptoms and functional outcomes, but the primary score related to these measures was the work/school dimension of the DAR. DAR scores were only weakly and nonsignificantly related to positive symptoms. This study provides preliminary support for the reliability and validity of the DAR using interviewer administration. The development of a patient reported version of the DAR using smart phone technology with automatic scoring is the next step. PMID:26712856

  17. Impact of Functional Appliances on Muscle Activity: A Surface Electromyography Study in Children

    PubMed Central

    Woźniak, Krzysztof; Piątkowska, Dagmara; Szyszka-Sommerfeld, Liliana; Buczkowska-Radlińska, Jadwiga

    2015-01-01

    Background Electromyography (EMG) is the most objective tool for assessing changes in the electrical activity of the masticatory muscles. The purpose of the study was to evaluate the tone of the masseter and anterior temporalis muscles in growing children before and after 6 months of treatment with functional removable orthodontic appliances. Material/Methods The sample conisted of 51 patients with a mean age 10.7 years with Class II malocclusion. EMG recordings were performed by using a DAB-Bluetooth instrument (Zebris Medical GmbH, Germany). Recordings were performed in mandibular rest position, during maximum voluntary contraction (MVC), and during maximum effort. Results The results of the study indicated that the electrical activity of the muscles in each of the clinical situations was the same in the group of girls and boys. The factor that determined the activity of the muscles was their type. In mandibular rest position and in MVC, the activity of the temporalis muscles was significantly higher that that of the masseter muscels. The maximum effort test indicated a higher fatigue in masseter than in temporalis muscles. Conclusions Surface electromyography is a useful tool for monitoring muscle activity. A 6-month period of functional therapy resulted in changes in the activity of the masticatory muscles. PMID:25600247

  18. The brain of opera singers: experience-dependent changes in functional activation.

    PubMed

    Kleber, B; Veit, R; Birbaumer, N; Gruzelier, J; Lotze, M

    2010-05-01

    Several studies have shown that motor-skill training over extended time periods results in reorganization of neural networks and changes in brain morphology. Yet, little is known about training-induced adaptive changes in the vocal system, which is largely subserved by intrinsic reflex mechanisms. We investigated highly accomplished opera singers, conservatory level vocal students, and laymen during overt singing of an Italian aria in a neuroimaging experiment. We provide the first evidence that the training of vocal skills is accompanied by increased functional activation of bilateral primary somatosensory cortex representing articulators and larynx. Opera singers showed additional activation in right primary sensorimotor cortex. Further training-related activation comprised the inferior parietal lobe and bilateral dorsolateral prefrontal cortex. At the subcortical level, expert singers showed increased activation in the basal ganglia, the thalamus, and the cerebellum. A regression analysis of functional activation with accumulated singing practice confirmed that vocal skills training correlates with increased activity of a cortical network for enhanced kinesthetic motor control and sensorimotor guidance together with increased involvement of implicit motor memory areas at the subcortical and cerebellar level. Our findings may have ramifications for both voice rehabilitation and deliberate practice of other implicit motor skills that require interoception.

  19. [Microbial activity and functional diversity in rhizosphere of cucumber under different subsurface drip irrigation scheduling].

    PubMed

    Li, Hua; He, Hong-Jun; Li, Teng-Fei; Zhang, Zi-Kun

    2014-08-01

    The effects of subsurface drip irrigation scheduling on microbial activity and functional diversity in rhizosphere of cucumber in solar greenhouse were studied in this paper. The results showed that the soil microbial biomass C and N, basal respiration, metabolic quotient and values of AWCD, Shannon and McIntosh indexes were increased at first and then decreased with the increase of irrigation water amount. The values of microbial C and N, basal respiration and metabolic quotient in I2 treatments were significantly higher than those in I1 treatments at the 0.8E(p) irrigation level. The numbers of bacteria, actinomyces and nitrogen-fixing bacteria, and the activities of urease, phosphatase, sucrase, catalase and polyhenoloxidase were significantly higher in the 0.8E(p) treatment than in the other treatments. The numbers of bacteria and nitrogen-fixing bacteria, the activities of urease, phosphatase and sucrase in I2 treatments were significantly higher than in I1 treatment, the actinomyces number and activities of catalase and polyhenoloxidase had no significant difference between I1 and I2 treatments, however, the fungi number in I2 treatments were significantly lower than in I2 treaments at the 0.8E(p) irrigation level. The microbial activity and functional diversity in rhizosphere of cucumber were strengthened in the I20.8E(p) treatment, meanwhile, the soil microflora was improved and the soil enzymes activities were enhanced, therefore, the cucumber growth was promoted as well.

  20. Antioxidant Effect of Melatonin on the Functional Activity of Colostral Phagocytes in Diabetic Women

    PubMed Central

    Fagundes, Danny L. G.; Calderon, Iracema M. P.; França, Eduardo L.

    2013-01-01

    Melatonin is involved in a number of physiological and oxidative processes, including functional regulation in human milk. The present study investigated the mechanisms of action of melatonin and its effects on the functional activity of colostral phagocytes in diabetic women. Colostrum samples were collected from normoglycemic (N = 38) and diabetic (N = 38) women. We determined melatonin concentration, superoxide release, bactericidal activity and intracellular Ca2+ release by colostral phagocytes treated or not with 8-(Diethylamino) octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) and incubated with melatonin and its precursor (N-acetyl-serotonin-NAS), antagonist (luzindole) and agonist (chloromelatonin-CMLT). Melatonin concentration was higher in colostrum samples from hyperglycemic than normoglycemic mothers. Melatonin stimulated superoxide release by colostral phagocytes from normoglycemic but not hyperglycemic women. NAS increased superoxide, irrespective of glycemic status, whereas CMTL increased superoxide only in cells from the normoglycemic group. Phagocytic activity in colostrum increased significantly in the presence of melatonin, NAS and CMLT, irrespective of glycemic status. The bactericidal activity of colostral phagocytes against enterophatogenic Escherichia coli (EPEC) increased in the presence of melatonin or NAS in the normoglycemic group, but not in the hyperglycemic group. Luzindole blocked melatonin action on colostrum phagocytes. Phagocytes from the normoglycemic group treated with melatonin exhibited an increase in intracellular Ca2+ release. Phagocytes treated with TMB-8 (intracellular Ca2+ inhibitor) decreased superoxide, bactericidal activity and intracellular Ca2+ release in both groups. The results obtained suggest an interactive effect of glucose metabolism and melatonin on colostral phagocytes. In colostral phagocytes from normoglycemic mothers, melatonin likely increases the ability of colostrum to protect against EPEC

  1. Cellular senescence checkpoint function determines differential Notch1-dependent oncogenic and tumor-suppressor activities.

    PubMed

    Kagawa, S; Natsuizaka, M; Whelan, K A; Facompre, N; Naganuma, S; Ohashi, S; Kinugasa, H; Egloff, A M; Basu, D; Gimotty, P A; Klein-Szanto, A J; Bass, A J; Wong, K-K; Diehl, J A; Rustgi, A K; Nakagawa, H

    2015-04-30

    Notch activity regulates tumor biology in a context-dependent and complex manner. Notch may act as an oncogene or a tumor-suppressor gene even within the same tumor type. Recently, Notch signaling has been implicated in cellular senescence. Yet, it remains unclear as to how cellular senescence checkpoint functions may interact with Notch-mediated oncogenic and tumor-suppressor activities. Herein, we used genetically engineered human esophageal keratinocytes and esophageal squamous cell carcinoma cells to delineate the functional consequences of Notch activation and inhibition along with pharmacological intervention and RNA interference experiments. When expressed in a tetracycline-inducible manner, the ectopically expressed activated form of Notch1 (ICN1) displayed oncogene-like characteristics inducing cellular senescence corroborated by the induction of G0/G1 cell-cycle arrest, Rb dephosphorylation, flat and enlarged cell morphology and senescence-associated β-galactosidase activity. Notch-induced senescence involves canonical CSL/RBPJ-dependent transcriptional activity and the p16(INK4A)-Rb pathway. Loss of p16(INK4A) or the presence of human papilloma virus (HPV) E6/E7 oncogene products not only prevented ICN1 from inducing senescence but permitted ICN1 to facilitate anchorage-independent colony formation and xenograft tumor growth with increased cell proliferation and reduced squamous-cell differentiation. Moreover, Notch1 appears to mediate replicative senescence as well as transforming growth factor-β-induced cellular senescence in non-transformed cells and that HPV E6/E7 targets Notch1 for inactivation to prevent senescence, revealing a tumor-suppressor attribute of endogenous Notch1. In aggregate, cellular senescence checkpoint functions may influence dichotomous Notch activities in the neoplastic context.

  2. Structure and Function of the 5'-<' Exoribonuclease Rat1 and its Activating Partner Rai1

    SciTech Connect

    Xiang, S.; Cooper-Morgan, A; Jiao, X; Kiledjian, M; Manley, J; Tong, L

    2009-01-01

    The 5??3? exoribonucleases (XRNs) comprise a large family of conserved enzymes in eukaryotes with crucial functions in RNA metabolism and RNA interference1, 2, 3, 4, 5. XRN2, or Rat1 in yeast6, functions primarily in the nucleus and also has an important role in transcription termination by RNA polymerase II (refs 7-14). Rat1 exoribonuclease activity is stimulated by the protein Rai1 (refs 15, 16). Here we report the crystal structure at 2.2 A resolution of Schizosaccharomyces pombe Rat1 in complex with Rai1, as well as the structures of Rai1 and its murine homologue Dom3Z alone at 2.0 A resolution. The structures reveal the molecular mechanism for the activation of Rat1 by Rai1 and for the exclusive exoribonuclease activity of Rat1. Biochemical studies confirm these observations, and show that Rai1 allows Rat1 to degrade RNAs with stable secondary structure more effectively. There are large differences in the active site landscape of Rat1 compared to related and PIN (PilT N terminus) domain-containing nucleases17, 18, 19, 20. Unexpectedly, we identified a large pocket in Rai1 and Dom3Z that contains highly conserved residues, including three acidic side chains that coordinate a divalent cation. Mutagenesis and biochemical studies demonstrate that Rai1 possesses pyrophosphohydrolase activity towards 5? triphosphorylated RNA. Such an activity is important for messenger RNA degradation in bacteria21, but this is, to our knowledge, the first demonstration of this activity in eukaryotes and suggests that Rai1/Dom3Z may have additional important functions in RNA metabolism.

  3. Upper limb function and activity in people with facioscapulohumeral muscular dystrophy: a web-based survey.

    PubMed

    Bergsma, Arjen; Cup, Edith H C; Janssen, Mariska M H P; Geurts, Alexander C H; de Groot, Imelda J M

    2017-02-01

    Purpose To investigate the upper extremity (UE) at the level of impairments and related activity limitations and participation restrictions in people with facioscapulohumeral muscular dystrophy (FSHD). Methods The study was conducted using web-based questionnaires that were distributed amongst people with FSHD in the Netherlands. Eighty-eight respondents started the survey, and 71 completed it. The questionnaires covered the following dimensions: Function, Activity and Participation of the International Classification of Functioning Disability and Health. Results More than 40% of the respondents experienced pain in one arm or both the arms. Increased pain and stiffness scores and longer disease duration were associated with increased limitation scores. For basic activities, lifting the arm above shoulder-level was most frequently reported as most limited, coherent with the clinical picture of FSHD. Among the respondents, 50% indicated restrictions at school, 78% indicated restrictions at work and more than 80% indicated restrictions whilst participating in sports, hobbies, household activities and romantic relationships. Conclusions This study has shown that alongside the well-known problem of lifting the arms above shoulder-level, UE activities below shoulder height during vocational and occupational activities are also problematic in patients with FSHD. Alongside disease duration, pain and stiffness are associated with UE activity limitations. Implications for Rehabilitation Attention is needed for pain and experienced stiffness in the upper extremity as it is frequently present in patients with FSHD. Rehabilitation professionals need to be aware that patients with FSHD not only experience problems with activities above shoulder height, but also with activities below shoulder height. At least 50% of the patients with FSHD experience restrictions in participation as a result of limitations in their UE.

  4. Suboptimal Muscle Synergy Activation Patterns Generalize their Motor Function across Postures.

    PubMed

    Sohn, M Hongchul; Ting, Lena H

    2016-01-01

    We used a musculoskeletal model to investigate the possible biomechanical and neural bases of using consistent muscle synergy patterns to produce functional motor outputs across different biomechanical conditions, which we define as generalizability. Experimental studies in cats demonstrate that the same muscle synergies are used during reactive postural responses at widely varying configurations, producing similarly-oriented endpoint force vectors with respect to the limb axis. However, whether generalizability across postures arises due to similar biomechanical properties or to neural selection of a particular muscle activation pattern has not been explicitly tested. Here, we used a detailed cat hindlimb model to explore the set of feasible muscle activation patterns that produce experimental synergy force vectors at a target posture, and tested their generalizability by applying them to different test postures. We used three methods to select candidate muscle activation patterns: (1) randomly-selected feasible muscle activation patterns, (2) optimal muscle activation patterns minimizing muscle effort at a given posture, and (3) generalizable muscle activation patterns that explicitly minimized deviations from experimentally-identified synergy force vectors across all postures. Generalizability was measured by the deviation between the simulated force direction of the candidate muscle activation pattern and the experimental synergy force vectors at the test postures. Force angle deviations were the greatest for the randomly selected feasible muscle activation patterns (e.g., >100°), intermediate for effort-wise optimal muscle activation patterns (e.g., ~20°), and smallest for generalizable muscle activation patterns (e.g., <5°). Generalizable muscle activation patterns were suboptimal in terms of effort, often exceeding 50% of the maximum possible effort (cf. ~5% in minimum-effort muscle activation patterns). The feasible muscle activation ranges of individual

  5. Suboptimal Muscle Synergy Activation Patterns Generalize their Motor Function across Postures

    PubMed Central

    Sohn, M. Hongchul; Ting, Lena H.

    2016-01-01

    We used a musculoskeletal model to investigate the possible biomechanical and neural bases of using consistent muscle synergy patterns to produce functional motor outputs across different biomechanical conditions, which we define as generalizability. Experimental studies in cats demonstrate that the same muscle synergies are used during reactive postural responses at widely varying configurations, producing similarly-oriented endpoint force vectors with respect to the limb axis. However, whether generalizability across postures arises due to similar biomechanical properties or to neural selection of a particular muscle activation pattern has not been explicitly tested. Here, we used a detailed cat hindlimb model to explore the set of feasible muscle activation patterns that produce experimental synergy force vectors at a target posture, and tested their generalizability by applying them to different test postures. We used three methods to select candidate muscle activation patterns: (1) randomly-selected feasible muscle activation patterns, (2) optimal muscle activation patterns minimizing muscle effort at a given posture, and (3) generalizable muscle activation patterns that explicitly minimized deviations from experimentally-identified synergy force vectors across all postures. Generalizability was measured by the deviation between the simulated force direction of the candidate muscle activation pattern and the experimental synergy force vectors at the test postures. Force angle deviations were the greatest for the randomly selected feasible muscle activation patterns (e.g., >100°), intermediate for effort-wise optimal muscle activation patterns (e.g., ~20°), and smallest for generalizable muscle activation patterns (e.g., <5°). Generalizable muscle activation patterns were suboptimal in terms of effort, often exceeding 50% of the maximum possible effort (cf. ~5% in minimum-effort muscle activation patterns). The feasible muscle activation ranges of individual

  6. IL23R(Arg381Gln) Functional Polymorphism Is Associated with Active Pulmonary Tuberculosis Severity

    PubMed Central

    Boukadida, Jalel

    2012-01-01

    The purpose of our study was to investigate the association between a functional single nucleotide polymorphism (SNP) in the interleukin-23 receptor gene (IL23R; rs11209026, 1142 Gwild type → Areduced function, Arg381Gln) and disease severity outcome in pulmonary tuberculosis (TB) in the Tunisian population. SNP was investigated in a population of 168 patients with active pulmonary TB (cases were stratified into patients with minimal/moderate lung involvement, i.e., patients with minimal/moderate disease [Pmd], and patients with extensive lung involvement, i.e., patients with active disease [Pad]) and 150 healthy subjects. Genotype analyses were carried out using the PCR-restriction fragment length polymorphism method. We have found that the IL23R reduced-function allele 1142A and genotypes AA and AG were overrepresented, especially in the Pad subgroup compared with the control group (51% versus 18% [P = 10−8], 33% versus 5% [P = 10−8], and 36% versus 26% [P = 5 × 10−3], respectively). Additionally, comparison of the Pad and the Pmd groups showed that the A allele and AA genotype seemed to be associated with 2.79-fold (P = 4 × 10−5) and 7.74-fold (P = 10−5) increased risks of TB with minimal/moderate lung involvement, respectively. Our results demonstrate that the reduced-function polymorphism 1142G → A encoded by IL23R influences the outcome of disease severity of active pulmonary TB in Tunisian patients. PMID:22695161

  7. Trait Approach and Avoidance Motivation: Lateralized Neural Activity Associated with Executive Function

    PubMed Central

    Spielberg, Jeffrey M.; Miller, Gregory A.; Engels, Anna S.; Herrington, John D.; Sutton, Bradley P.; Banich, Marie T.; Heller, Wendy

    2010-01-01

    Motivation and executive function are both necessary for the completion of goal-directed behavior. Research investigating the manner in which these processes interact is beginning to emerge and has implicated middle frontal gyrus (MFG) as a site of interaction for relevant neural mechanisms. However, this research has focused on state motivation, and it has not examined functional lateralization. The present study examined the impact of trait levels of approach and avoidance motivation on neural processes associated with executive function. Functional magnetic resonance imaging was conducted while participants performed a color-word Stroop task. Analyses identified brain regions in which trait approach and avoidance motivation (measured by questionnaires) moderated activation associated with executive control. Approach was hypothesized to be associated with left-lateralized MFG activation, whereas avoidance was hypothesized to be associated with right-lateralized MFG activation. Results supported both hypotheses. Present findings implicate areas of middle frontal gyrus in top-down control to guide behavior in accordance with motivational goals. PMID:20728552

  8. Association between physical activity in daily life and pulmonary function in adult smokers

    PubMed Central

    Barboza, Miriane Lilian; Barbosa, Alan Carlos Brisola; Spina, Giovanna Domingues; Sperandio, Evandro Fornias; Arantes, Rodolfo Leite; Gagliardi, Antonio Ricardo de Toledo; Romiti, Marcello; Dourado, Victor Zuniga

    2016-01-01

    Objective: To determine whether the level of physical activity in daily life (PADL) is associated with pulmonary function in adult smokers. Methods: We selected 62 adult smokers from among the participants of an epidemiological study conducted in the city of Santos, Brazil. The subjects underwent forced spirometry for pulmonary function assessment. The level of PADL was assessed by the International Physical Activity Questionnaire and triaxial accelerometry, the device being used for seven days. The minimum level of PADL, in terms of quantity and intensity, was defined as 150 min/week of moderate to vigorous physical activity. Correlations between the studied variables were tested with Pearson's or Spearman's correlation coefficient, depending on the distribution of the variables. We used linear multiple regression in order to analyze the influence of PADL on the spirometric variables. The level of significance was set at 5%. Results: Evaluating all predictors, corrected for confounding factors, and using pulmonary function data as outcome variables, we found no significant associations between physical inactivity, as determined by accelerometry, and spirometric indices. The values for FVC were lower among the participants with arterial hypertension, and FEV1/FVC ratios were lower among those with diabetes mellitus. Obese participants and those with dyslipidemia presented with lower values for FVC and FEV1. Conclusions: Our results suggest that there is no consistent association between physical inactivity and pulmonary function in adult smokers. Smoking history should be given special attention in COPD prevention strategies, as should cardiovascular and metabolic comorbidities. PMID:27167434

  9. Trait approach and avoidance motivation: lateralized neural activity associated with executive function.

    PubMed

    Spielberg, Jeffrey M; Miller, Gregory A; Engels, Anna S; Herrington, John D; Sutton, Bradley P; Banich, Marie T; Heller, Wendy

    2011-01-01

    Motivation and executive function are both necessary for the completion of goal-directed behavior. Research investigating the manner in which these processes interact is beginning to emerge and has implicated middle frontal gyrus (MFG) as a site of interaction for relevant neural mechanisms. However, this research has focused on state motivation, and it has not examined functional lateralization. The present study examined the impact of trait levels of approach and avoidance motivation on neural processes associated with executive function. Functional magnetic resonance imaging was conducted while participants performed a color-word Stroop task. Analyses identified brain regions in which trait approach and avoidance motivation (measured by questionnaires) moderated activation associated with executive control. Approach was hypothesized to be associated with left-lateralized MFG activation, whereas avoidance was hypothesized to be associated with right-lateralized MFG activation. Results supported both hypotheses. Present findings implicate areas of middle frontal gyrus in top-down control to guide behavior in accordance with motivational goals.

  10. Effect of computerized cognitive rehabilitation program on cognitive function and activities of living in stroke patients.

    PubMed

    Yoo, Chanuk; Yong, Mi-Hyun; Chung, Jaeyeop; Yang, Yeongae

    2015-08-01

    [Purpose] The objective of this study was to examine the effect of cognitive rehabilitation using a computer on cognitive function and activities of daily living in stroke patients presenting impairment of cognitive function. [Subjects] Forty-six stroke patients were divided into two groups (a training group and control group) through random assignment. [Methods] The training group received rehabilitation therapy and an additional computerized cognitive rehabilitation program using The RehaCom software 30 minutes/day, 5 times/week for 5 weeks. The control group received only rehabilitation therapy including physical and occupational therapy. A comparative analysis on all subjects was conducted before and after the experiment using a cognitive test and activities of daily living test. [Results] After 5 weeks of therapy, the training group presented statistically significant improvement in cognitive function assessment items of digit span, visual span, visual learning, auditory continuous performance, visual continuous performance, and others compared with the control group but did not present statistically significant improvement in activities of daily living. [Conclusion] It was revealed through this study that computerized cognitive rehabilitation with the RehaCom program results in improvement in cognitive function and can be used as a treatment tool beneficial to stroke patients presenting cognitive impairment.

  11. Effect of computerized cognitive rehabilitation program on cognitive function and activities of living in stroke patients

    PubMed Central

    Yoo, Chanuk; Yong, Mi-hyun; Chung, Jaeyeop; Yang, Yeongae

    2015-01-01

    [Purpose] The objective of this study was to examine the effect of cognitive rehabilitation using a computer on cognitive function and activities of daily living in stroke patients presenting impairment of cognitive function. [Subjects] Forty-six stroke patients were divided into two groups (a training group and control group) through random assignment. [Methods] The training group received rehabilitation therapy and an additional computerized cognitive rehabilitation program using The RehaCom software 30 minutes/day, 5 times/week for 5 weeks. The control group received only rehabilitation therapy including physical and occupational therapy. A comparative analysis on all subjects was conducted before and after the experiment using a cognitive test and activities of daily living test. [Results] After 5 weeks of therapy, the training group presented statistically significant improvement in cognitive function assessment items of digit span, visual span, visual learning, auditory continuous performance, visual continuous performance, and others compared with the control group but did not present statistically significant improvement in activities of daily living. [Conclusion] It was revealed through this study that computerized cognitive rehabilitation with the RehaCom program results in improvement in cognitive function and can be used as a treatment tool beneficial to stroke patients presenting cognitive impairment. PMID:26355244

  12. Locally Estimated Hemodynamic Response Function and Activation Detection Sensitivity in Heroin-Cue Reactivity Study

    PubMed Central

    Maleki-Balajoo, Somayeh; Hossein-Zadeh, Gholam-Ali; Soltanian-Zadeh, Hamid; Ekhtiari, Hamed

    2016-01-01

    Introduction: A fixed hemodynamic response function (HRF) is commonly used for functional magnetic resonance imaging (fMRI) analysis. However, HRF may vary from region to region and subject to subject. We investigated the effect of locally estimated HRF (in functionally homogenous parcels) on activation detection sensitivity in a heroin cue reactivity study. Methods: We proposed a novel exploratory method for brain parcellation based on a probabilistic model to segregate the brain into spatially connected and functionally homogeneous components. Then, we estimated HRF and detected activated regions in response to an experimental task in each parcel using a joint detection estimation (JDE) method. We compared the proposed JDE method with the general linear model (GLM) that uses a fixed HRF and is implemented in FEAT (as a part of FMRIB Software Library, version 4.1). Results: 1) Regions detected by JDE are larger than those detected by fixed HRF, 2) In group analysis, JDE found areas of activation not detected by fixed HRF. It detected drug craving a priori “regions-of-interest” in the limbic lobe (anterior cingulate cortex [ACC], posterior cingulate cortex [PCC] and cingulate gyrus), basal ganglia, especially striatum (putamen and head of caudate), and cerebellum in addition to the areas detected by the fixed HRF method, 3) JDE obtained higher Z-values of local maxima compared to those obtained by fixed HRF. Conclusion: In our study of heroin cue reactivity, our proposed method (that estimates HRF locally) outperformed the conventional GLM that uses a fixed HRF. PMID:27872691

  13. Function of Piwi, a nuclear Piwi/Argonaute protein, is independent of its slicer activity

    PubMed Central

    Darricarrère, Nicole; Liu, Na; Watanabe, Toshiaki; Lin, Haifan

    2013-01-01

    The Piwi protein subfamily is essential for Piwi-interacting RNA (piRNA) biogenesis, transposon silencing, and germ-line development, all of which have been proposed to require Piwi endonuclease activity, as validated for two cytoplasmic Piwi proteins in mice. However, recent evidence has led to questioning of the generality of this mechanism for the Piwi members that reside in the nucleus. Drosophila offers a distinct opportunity to study the function of nuclear Piwi proteins because, among three Drosophila Piwi proteins—called Piwi, Aubergine, and Argonaute 3—Piwi is the only member of this subfamily that is localized in the nucleus and expressed in both germ-line and somatic cells in the gonad, where it is responsible for piRNA biogenesis and regulatory functions essential for fertility. In this study, we demonstrate beyond doubt that the slicer activity of Piwi is not required for any known functions in vivo. We show that, in transgenic flies with the DDX catalytic triad of PIWI mutated, neither primary nor secondary piRNA biogenesis is detectably affected, transposons remain repressed, and fertility is normal. Our observations demonstrate that the mechanism of Piwi is independent of its in vitro endonuclease activity. Instead, it is consistent with the alternative mode of Piwi function as a molecule involved in the piRNA-directed guidance of epigenetic factors to chromatin. PMID:23297219

  14. Targeting complement activation in brain-dead donors improves renal function after transplantation.

    PubMed

    Damman, Jeffrey; Hoeger, Simone; Boneschansker, Leo; Theruvath, Ashok; Waldherr, Ruediger; Leuvenink, Henri G; Ploeg, Rutger J; Yard, Benito A; Seelen, Marc A

    2011-05-01

    Kidneys recovered from brain-dead donors have inferior outcomes after transplantation compared to kidneys from living donors. Since complement activation plays an important role in renal transplant related injury, targeting complement activation in brain-dead donors might improve renal function after transplantation. Brain death (BD) was induced in Fisher rats by inflation of an epidurally placed balloon catheter and ventilated for 6h. BD animals were treated with soluble complement receptor 1 (sCR1) 1h before or 1h after BD. Kidney transplantation was performed and 7 days after transplantation animals were sacrificed. Plasma creatinine and urea were measured at days 0, 1, 3, 5 and 7 after transplantation. Renal function was significantly better at day 1 after transplantation in recipients receiving a sCR1 pre-treated donor kidney compared to recipients of a non-treated donor graft. Also treatment with sCR1, 1h after the diagnosis of BD, resulted in a better renal function after transplantation. Gene expression of IL-6, IL-1beta and TGF-beta were significantly lower in renal allografts recovered from treated donors. This study shows that targeting complement activation, during BD in the donor, leads to an improved renal function after transplantation in the recipient.

  15. Involvement of TREK-1 activity in astrocyte function and neuroprotection under simulated ischemia conditions.

    PubMed

    Wu, Xiao; Liu, Yang; Chen, Xiaojing; Sun, Qian; Tang, Ronghua; Wang, Wei; Yu, Zhiyuan; Xie, Minjie

    2013-03-01

    Astrocytes play a fundamental role in the pathogenesis of ischemic neuronal death. The optimal operation of electrogenic astrocytic transporters and exchangers for some well-defined astrocyte brain homeostatic functions depends on the presence of K(+) channels in the cell membranes and the hyperpolarized membrane potential. Our previous study showed that astrocytes functionally express two-pore domain K(+) channel TREK-1, which helps to set the negative resting membrane potential. However, the roles of TREK-1 on astrocytic function under normal and ischemic conditions remain unclear. In this study, we investigated the expression of TREK-1 protein on cultured astrocytes and the effect of TREK-1 activity on astrocytic glutamate clearance capacity and release of s100β after simulated ischemic insult. TREK-1 immunoreactivity was up-regulated after hypoxia. Suppression of TREK-1 activity inhibited the glutamate clearance capability, enhanced the inflammatory secretion of astrocytes derived s100β and led to increased neuronal apoptosis after ischemic insult. Our results suggest that TREK-1 activity is involved in astrocytic function and neuronal survival. This would provide evidence showing astrocytic TREK-1 involvement in ischemia pathology which may serve as a potential therapeutic target in stroke.

  16. Serotonin2c receptor constitutive activity: in vivo direct and indirect evidence and functional significance.

    PubMed

    Navailles, Sylvia; Lagière, Mélanie; Guthrie, Martin; De Deurwaerdère, Philippe

    2013-06-01

    Serotonin2c (5-HT2c) receptors are widely expressed in the central nervous system where they play a pivotal role in the regulation of neuronal network excitability. Along with this fundamental physiological function, 5-HT2c receptors are thought to be implicated in the pathophysiology of several neuropsychiatric disorders and have become a major pharmacological target for the development of improved treatments of these disorders. In the past decade, many studies have focused on the constitutive activity of 5-HT2c receptors and the therapeutic potential of drugs acting as inverse agonists. Although the constitutive activity of the 5-HT2c receptor has been clearly described in vitro, the transposition of this concept to living animals is often difficult to ascertain. Nevertheless, cumulating evidence has demonstrated the functional relevance of such property in regulating physiological systems in vivo both at the level of the central and peripheral nervous systems. The present review provides an update of the growing number of studies that show, by means of pharmacological tools, the participation of the constitutive activity of 5-HT2c receptors in the control of various biochemical and behavioural functions in vivo and emphasizes the functional organization of this constitutive control together with the phasic and tonic (involving the spontaneous release of 5-HT) modalities of the 5-HT2c receptor in the brain.

  17. Functional coupling of simultaneous electrical and metabolic activity in the human brain.

    PubMed

    Oakes, Terrence R; Pizzagalli, Diego A; Hendrick, Andrew M; Horras, Katherine A; Larson, Christine L; Abercrombie, Heather C; Schaefer, Stacey M; Koger, John V; Davidson, Richard J

    2004-04-01

    The relationships between brain electrical and metabolic activity are being uncovered currently in animal models using invasive methods; however, in the human brain this relationship remains not well understood. In particular, the relationship between noninvasive measurements of electrical activity and metabolism remains largely undefined. To understand better these relations, cerebral activity was measured simultaneously with electroencephalography (EEG) and positron emission tomography using [(18)f]-fluoro-2-deoxy-D-glucose (PET-FDG) in 12 normal human subjects during rest. Intracerebral distributions of current density were estimated, yielding tomographic maps for seven standard EEG frequency bands. The PET and EEG data were registered to the same space and voxel dimensions, and correlational maps were created on a voxel-by-voxel basis across all subjects. For each band, significant positive and negative correlations were found that are generally consistent with extant understanding of EEG band power function. With increasing EEG frequency, there was an increase in the number of positively correlated voxels, whereas the lower alpha band (8.5-10.0 Hz) was associated with the highest number of negative correlations. This work presents a method for comparing EEG signals with other more traditionally tomographic functional imaging data on a 3-D basis. This method will be useful in the future when it is applied to functional imaging methods with faster time resolution, such as short half-life PET blood flow tracers and functional magnetic resonance imaging.

  18. Globus Pallidus Interna in Tourette Syndrome: Decreased Local Activity and Disrupted Functional Connectivity

    PubMed Central

    Ji, Gong-Jun; Liao, Wei; Yu, Yang; Miao, Huan-Huan; Feng, Yi-Xuan; Wang, Kai; Feng, Jian-Hua; Zang, Yu-Feng

    2016-01-01

    Globus pallidus interna (GPi) is an effective deep brain stimulation site for the treatment of Tourette syndrome (TS), and plays a crucial role in the pathophysiology of TS. To investigate the functional network feature of GPi in TS patients, we retrospectively studied 24 boys with ‘pure’ TS and 32 age-/education-matched healthy boys by resting state functional magnetic resonance images. Amplitude of low-frequency fluctuation (ALFF) and functional connectivity were used to estimate the local activity in GPi and its functional coordinate with the whole brain regions, respectively. We found decreased ALFF in patients’ bilateral GPi, which was also negatively correlated with clinical symptoms. Functional connectivity analysis indicated abnormal regions within motor and motor-control networks in patients (inferior part of sensorimotor area, cerebellum, prefrontal cortex, cingulate gyrus, caudate nucleus, and brain stem). Transcranial magnetic stimulation sites defined by previous studies (“hand knob” area, premotor area, and supplementary motor area) did not show significantly different functional connectivity with GPi between groups. In summary, this study characterized the disrupted functional network of GPi and provided potential regions-of-interest for further basic and clinical studies on TS. PMID:27799898

  19. Functional capacity and assistance from the caregiver during daily activities in Brazilian children with cerebral palsy

    PubMed Central

    2013-01-01

    Background Cerebral Palsy (CP) presents changes in posture and movement as a core characteristic, which requires multiprofessional clinical treatments during children’s habilitation or rehabilitation. Besides clinical treatment, it is fundamental that professionals use evaluation systems to quantify the difficulties presented to the individual and their families in their daily lives. We aimed to investigate the functional capacity of individuals with CP and the amount of assistance required by the caregiver in day-to-day activities. Methods Twenty patients with CP, six-year-old on average, were evaluated. The Pediatric Evaluation Inventory of Incapacities was used (PEDI - Pediatric Evaluation Disability Inventory), a system adapted for Brazil that evaluates child's dysfunction in three 3 dimensions: self-care, mobility and social function. To compare the three areas, repeated measures analysis of variance (ANOVA) were used. Results We found the following results regarding the functional capacity of children: self-care, 27.4%, ±17.5; mobility, 25.8%, ±33.3 and social function, 36.3%, ±27.7. The results of the demand of aid from the caregiver according to each dimension were: self-care, 9.7%, ±19.9; mobility, 14.1%, ± 20.9 and social function, 19.8%, ±26.1. Conclusion We indicated that there was no difference between the performance of the subjects in areas of self-care, mobility and social function considering the functional skills and assistance required by the caregiver. PMID:23302576

  20. Pain-inducing imagery as a function of hypnotisability and of the activity of Gray's Behavioral Inhibition/Activation Systems.

    PubMed

    Santarcangelo, Enrica L; Varanini, Maurizio; Paoletti, Giulia; Castellani, Eleonora; Palombo, Carlo; Carli, Giancarlo

    2013-12-17

    The aim of the study was to test the efficacy of pain imagery as a function of hypnotisability and of the activity of Behavioral Inhibition/Activation Systems. Questionnaires of imagery abilities (Betts) for the visual, cutaneous and organic modalities, absorption in cognitive tasks (TAS), proneness to inhibit stressful/painful experience/seek out positive experiences (BIS BAS), trait anxiety (STAI-Y2) and psychological well-being (PWB) were administered to 21 subjects with high hypnotisability (highs) and 21 subjects with low hypnotisability (lows). Self-reports of pain intensity and of neutral tactile perception were collected during imagery of nociceptive (Pain) and neutral tactile stimulation (NT). ECG and skin conductance were recorded. Highs exhibited greater imagery abilities, absorption, Behavioral Inhibition System Activity and psychological well-being with respect to lows. They reported lower scores of pain intensity than of tactile perception, while in lows Pain and NT scores did not differ. However, controlling for BAS, but not for BIS, revealed differences in the efficacy of pain imagery between highs and lows. Heart rate decreased in both tasks and groups; heart rate variability and skin conductance did not change significantly during imageries. Our findings suggest that the Behavioral Inhibition/Activation Systems interact with imagery abilities reducing the efficacy of pain imagery and prompt investigation of possible similar interactions in the modulation of physically induced experimental pain and of chronic pain in the general population.

  1. Reconstructing ecosystem functions of the active microbial community of the Baltic Sea oxygen depleted sediments

    PubMed Central

    Franzetti, Andrea; Lundin, Daniel; Sjöling, Sara

    2016-01-01

    Baltic Sea deep water and sediments hold one of the largest anthropogenically induced hypoxic areas in the world. High nutrient input and low water exchange result in eutrophication and oxygen depletion below the halocline. As a consequence at Landsort Deep, the deepest point of the Baltic Sea, anoxia in the sediments has been a persistent condition over the past decades. Given that microbial communities are drivers of essential ecosystem functions we investigated the microbial community metabolisms and functions of oxygen depleted Landsort Deep sediments by metatranscriptomics. Results show substantial expression of genes involved in protein metabolism demonstrating that the Landsort Deep sediment microbial community is active. Identified expressed gene suites of metabolic pathways with importance for carbon transformation including fermentation, dissimilatory sulphate reduction and methanogenesis were identified. The presence of transcripts for these metabolic processes suggests a potential for heterotrophic-autotrophic community synergism and indicates active mineralisation of the organic matter deposited at the sediment as a consequence of the eutrophication process. Furthermore, cyanobacteria, probably deposited from the water column, are transcriptionally active in the anoxic sediment at this depth. Results also reveal high abundance of transcripts encoding integron integrases. These results provide insight into the activity of the microbial community of the anoxic sediment at the deepest point of the Baltic Sea and its possible role in ecosystem functioning. PMID:26823996

  2. Effects of selective REM sleep deprivation on prefrontal gamma activity and executive functions.

    PubMed

    Corsi-Cabrera, M; Rosales-Lagarde, A; del Río-Portilla, Y; Sifuentes-Ortega, R; Alcántara-Quintero, B

    2015-05-01

    Given that the dorsolateral prefrontal cortex is involved in executive functions and is deactivated and decoupled from posterior associative regions during REM sleep, that Gamma temporal coupling involved in information processing is enhanced during REM sleep, and that adult humans spend about 90 min of every 24h in REM sleep, it might be expected that REM sleep deprivation would modify Gamma temporal coupling and have a deteriorating effect on executive functions. We analyzed EEG Gamma activity and temporal coupling during implementation of a rule-guided task before and after REM sleep deprivation and its effect on verbal fluency, flexible thinking and selective attention. After two nights in the laboratory for adaptation, on the third night subjects (n=18) were randomly assigned to either selective REM sleep deprivation effectuated by awakening them at each REM sleep onset or, the same number of NREM sleep awakenings as a control for unspecific effects of sleep interruptions. Implementation of abstract rules to guide behavior required greater activation and synchronization of Gamma activity in the frontopolar regions after REM sleep reduction from 20.6% at baseline to just 3.93% of total sleep time. However, contrary to our hypothesis, both groups showed an overall improvement in executive task performance and no effect on their capacity to sustain selective attention. These results suggest that after one night of selective REM sleep deprivation executive functions can be compensated by increasing frontal activation and they still require the participation of supervisory control by frontopolar regions.

  3. Verbal working memory load affects prefrontal cortices activation: evidence from a functional NIRS study in humans

    NASA Astrophysics Data System (ADS)

    Li, Chengjun; Gong, Hui; Zeng, Shaoqun; Luo, Qingming

    2005-03-01

    Working memory (WM) refers to the temporary maintenance of information that is no longer accessible in the environment, and the manipulation of this information for subsequent use. PET and functional MRI studies suggest that prefrontal cortex (PFC) is involved in WM. Here, we report a functional near-infrared spectroscopy (NIRS) study on the PFC activation caused by a WM task, a verbal n-back task. During performance of the task, concentration changes of oxy-Hb (HbO2), deoxy-Hb (Hb), and total-Hb (HbT) in subjects" prefrontal cortex were monitored by a 24-channel functional NIRS imager. The behavioral performances (accuracy and response time) were recorded simultaneously. Results revealed that as memory load increased, subjects showed poorer behavioral performance as well as monotonously increasing magnitudes of the activations in the left ventrolateral PFC (VLPFC) and bilateral dorsolateral PFC (DLPFC). In addition, the analysis of comparison between subjects showed that certain relations likely exist between the cerebral activation and the performance parameters for an individual subject: lower accuracy is accompanied by longer response time and further activation. Such means that the subject with difficulty in solving a problem will demonstrate more significant hemodynamic changes compared with the subject without difficulty in solving the same problem.

  4. The relation of childhood physical activity and aerobic fitness to brain function and cognition: a review.

    PubMed

    Khan, Naiman A; Hillman, Charles H

    2014-05-01

    Physical inactivity has been shown to increase the risk for several chronic diseases across the lifespan. However, the impact of physical activity and aerobic fitness on childhood cognitive and brain health has only recently gained attention. The purposes of this article are to: 1) highlight the recent emphasis for increasing physical activity and aerobic fitness in children's lives for cognitive and brain health; 2) present aspects of brain development and cognitive function that are susceptible to physical activity intervention; 3) review neuroimaging studies examining the cross-sectional and experimental relationships between aerobic fitness and executive control function; and 4) make recommendations for future research. Given that the human brain is not fully developed until the third decade of life, preadolescence is characterized by changes in brain structure and function underlying aspects of cognition including executive control and relational memory. Achieving adequate physical activity and maintaining aerobic fitness in childhood may be a critical guideline to follow for physical as well as cognitive and brain health.

  5. Hand function and performance of daily activities in systemic lupus erythematosus: a clinical study.

    PubMed

    Malcus Johnsson, P; Sandqvist, G; Nilsson, J-Å; Bengtsson, A A; Sturfelt, G; Nived, O

    2015-07-01

    This clinical study was performed to investigate hand problems in individuals with systemic lupus erythematosus (SLE) in comparison with healthy controls, and to explore problems in the performance of daily activities related to these hand problems, in order to objectify findings from a previous mail survey. We also investigated whether a simple hand test could detect hand problems in SLE. All individuals, 71 with SLE and 71 healthy controls, were examined for manifestations in body structures and body functions of the hands with a study-specific protocol. The simple hand test was performed by all the individuals and the arthritis impact measurement scale (AIMS 2) questionnaire was completed by the SLE individuals. In the SLE group, 58% had some kind of difficulty in the simple hand test, compared with 8% in the control group. Fifty percent of the SLE individuals experienced problems in performing daily activities due to hand deficits. Pain in the hands, reduced strength and dexterity, Raynaud's phenomenon and trigger finger were the most prominent body functions affecting the performance of daily activities. Deficits in hand function are common in SLE and affect the performance of daily activities. The simple hand test may be a useful tool in detecting hand problems.

  6. Characterization of nitric oxide synthase activity in sheep urinary tract: functional implications.

    PubMed Central

    García-Pascual, A.; Costa, G.; Labadia, A.; Persson, K.; Triguero, D.

    1996-01-01

    1. To define further the role of nitric oxide (NO) in urinary tract function, we have measured the presence of nitric oxide synthase (NOS) activity, and its relationship with functional NO-mediated responses to electrical field stimulation (EFS) in the urethra, the detrusor and the ureter from sheep. NOS activity was assayed by the conversion of L-[14C]-arginine to L-[14C]-citrulline. Endogenous production of citrulline was confirmed by thin layer chromatography. 2. NOS enzymatic activity was detected in the cytosolic fraction from tissue homogenates with the following regional distribution (pmol citrulline mg-1 protein min-1): urethra (33 +/- 3.3), detrusor (13.1 +/- 1.1) and ureter (1.5 +/- 0.2). No activity was detected in the particulate fraction of any region. 3. NOS activity was dependent on Ca(2+)-calmodulin and required exogenously added NADPH and tetrahydrobyoptein (BH4) for maximal activity. Exclusion of calmodulin from the incubation mixture did not modify NOS activity, but it was significantly reduced in the presence of the calmodulin antagonist, calmidazolium, suggesting the presence of enough endogenous calmodulin to sustain the observed NOS activity. 4. NOS activity was inhibited to a greater extent by NG-nitro-L-arginine (L-NOARG) and its methyl ester (L-NAME) than by NG-monomethyl-L-arginine (L-NMMA), while 7-nitroindazole (7-NI) was a weak inhibitor and L-cannavine had no effect. 5. Citrulline formation could be inhibited by superoxide dismutase in an oxyhaemoglobin-sensitive manner, suggesting feedback inhibition of NOS by NO. 6. EFS induced prominent NO-mediated relaxations in the urethra while minor or no responses were observed in the detrusor and the ureter, respectively. Urethral relaxations to EFS were inhibited by NOS inhibitors with the rank order of potency: L-NOARG = L-NAME > 7-NI > L-NMMA. 7. In conclusion, we have demonstrated the presence of NO-synthesizing enzymatic activity in the sheep urinary tract which shows similar

  7. Sexual activity and function in women more than 2 years after midurethral sling placement

    PubMed Central

    Zyczynski, Halina M.; Rickey, Leslie; Dyer, Keisha Y.; Wilson, Tracey; Stoddard, Anne M.; Gormley, E. Ann; Hsu, Yvonne; Kusek, John W.; Brubaker, Linda

    2013-01-01

    OBJECTIVE The purpose of this study was to assess prospectively the effects of midurethral sling surgery on sexual function and activity. STUDY DESIGN Sexual activity and function was assessed in 597 women with stress urinary incontinence who were enrolled in a randomized equivalence trial of retropubic compared with transobturator midurethral slings. Repeated measures analysis of variance was used to assess changes in Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire scores over a 2-year period. RESULTS Significant, similar improvements in sexual function were seen in both midurethral sling groups. Mean Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire scores increased from 32.8 at baseline to 37.6 at 6 months and 37.3 at 24 months (P < .0001). Dyspareunia, incontinence during sex, and fear of incontinence during sex each significantly improved after surgery. Preoperative urge incontinence was associated with abstinence after surgery (P = .02); postoperative urge incontinence negatively impacted sexual function (P = .047). CONCLUSION Midurethral sling surgery for stress urinary incontinence significantly improves sexual function, although coexistent urge incontinence has a negative impact. PMID:22840975

  8. Physical Activity and Brain Function in Older Adults at Increased Risk for Alzheimer’s Disease

    PubMed Central

    Smith, J. Carson; Nielson, Kristy A.; Woodard, John L.; Seidenberg, Michael; Rao, Stephen M.

    2013-01-01

    Leisure-time physical activity (PA) and exercise training are known to help maintain cognitive function in healthy older adults. However, relatively little is known about the effects of PA on cognitive function or brain function in those at increased risk for Alzheimer’s disease through the presence of the apolipoproteinE epsilon4 (APOE-ε4) allele, diagnosis of mild cognitive impairment (MCI), or the presence of metabolic disease. Here, we examine the question of whether PA and exercise interventions may differentially impact cognitive trajectory, clinical outcomes, and brain structure and function among individuals at the greatest risk for AD. The literature suggests that the protective effects of PA on risk for future dementia appear to be larger in those at increased genetic risk for AD. Exercise training is also effective at helping to promote stable cognitive function in MCI patients, and greater cardiorespiratory fitness is associated with greater brain volume in early-stage AD patients. In APOE-ε4 allele carriers compared to non-carriers, greater levels of PA may be more effective in reducing amyloid burden and are associated with greater activation of semantic memory-related neural circuits. A greater research emphasis should be placed on randomized clinical trials for exercise, with clinical, behavioral, and neuroimaging outcomes in people at increased risk for AD. PMID:24961307

  9. MOOD STATES, SYMPATHETIC ACTIVITY, AND IN VIVO β-ADRENERGIC RECEPTOR FUNCTION IN A NORMAL POPULATION

    PubMed Central

    Yu, Bum-Hee; Kang, Eun-Ho; Ziegler, Michael G.; Mills, Paul J.; Dimsdale, Joel E.

    2009-01-01

    The purpose of this study was to examine the relationship between mood states and β-adrenergic receptor function in a normal population. We also examined if sympathetic nervous system activity is related to mood states or β-adrenergic receptor function. Sixty-two participants aged 25–50 years were enrolled in this study. Mood states were assessed using the Profile of Mood States (POMS). β-adrenergic receptor function was determined using the chronotropic 25 dose isoproterenol infusion test. Level of sympathetic nervous system activity was estimated from 24-hr urine norepinephrine excretion. Higher tension-anxiety, depression-dejection, and anger-hostility were related to decreased β-adrenergic receptor sensitivity (i.e., higher chronotropic 25 dose values), but tension-anxiety was the only remaining independent predictor of β-adrenergic receptor function after controlling for age, gender, ethnicity, and body mass index (BMI). Urinary norepinephrine excretion was unrelated to either mood states or β-adrenergic receptor function. These findings replicate previous reports that anxiety is related to decreased (i.e., desensitized) β-adrenergic receptor sensitivity, even after controlling for age, gender, ethnicity, and body mass index. PMID:17583588

  10. Estimating time-correlation functions by sampling and unbiasing dynamically activated events.

    PubMed

    Athènes, Manuel; Marinica, Mihai-Cosmin; Jourdan, Thomas

    2012-11-21

    Transition path sampling is a rare-event method that estimates state-to-state time-correlation functions in many-body systems from samples of short trajectories. In this framework, it is proposed to bias the importance function using the lowest Jacobian eigenvalue moduli along the dynamical trajectory. A lowest eigenvalue modulus is related to the lowest eigenvalue of the Hessian matrix and is evaluated here using the Lanczos algorithm as in activation-relaxation techniques. This results in favoring the sampling of activated trajectories and enhancing the occurrence of the rare reactive trajectories of interest, those corresponding to transitions between locally stable states. Estimating the time-correlation functions involves unbiasing the sample of simulated trajectories which is done using the multi-state Bennett acceptance ratio (MBAR) method. To assess the performance of our procedure, we compute the time-correlation function associated with the migration of a vacancy in α-iron. The derivative of the estimated time-correlation function yields a migration rate in agreement with the one given by transition state theory. Besides, we show that the information relative to rejected trajectories can be recycled within MBAR, resulting in a substantial speed-up. Unlike original transition path-sampling, our approach does not require computing the reversible work to confine the trajectory endpoints to a reactive state.

  11. Oral iodinated activated charcoal improves lung function in patients with COPD.

    PubMed

    Skogvall, Staffan; Erjefält, Jonas S; Olin, Anders I; Ankerst, Jaro; Bjermer, Leif

    2014-06-01

    The effect of 8 weeks treatment with oral iodinated activated charcoal (IAC) on lung function of patients with moderate chronic obstructive pulmonary disease (COPD) was examined in a double blind randomized placebo controlled parallel group study with 40 patients. In the IAC group, patients showed a statistically significant improvement of FEV1 baseline by 130 ml compared to placebo, corresponding to 8.2% improvement (p = 0.031*). Correlation statistics revealed that the improvement of FEV1 baseline was significantly correlated both to FEV1 post-bronchodilator (p = 0.0020**) and FEV1 post-exercise (0.033*) values. This demonstrates that the improved baseline lung function by IAC did not inhibit a further beta2-adrenoceptor relaxation, and thus that patients did not reach a limit for maximal improvement of the lung function after IAC treatment. Eight patients in the IAC group developed abnormal thyroid hormone levels transiently during the treatment. This side effect was not correlated to improvement of lung function (p = 0.82). No serious adverse effects directly related to the treatment were recorded. In summary, this study demonstrates that iodinated activated charcoal surprisingly and significantly improved lung function of patients with moderate COPD. The underlying mechanism of action is unclear, but is likely to be different from the drugs used today. The immediate conclusion is that further studies are now justified in order to determine clinical efficacy of IAC in COPD and explore possible mechanisms of action.

  12. Maternal Immune Activation Leads to Selective Functional Deficits in Offspring Parvalbumin Interneurons

    PubMed Central

    Canetta, Sarah; Bolkan, Scott; Padilla-Coreano, Nancy; Song, LouJin; Sahn, Ryan; Harrison, Neil; Gordon, Joshua A.; Brown, Alan; Kellendonk, Christoph

    2015-01-01

    Summary Abnormalities in prefrontal GABAergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, and was not observed in calretinin-expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to maternal immune activation, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders. PMID:26830140

  13. Passport, a native Tc1 transposon from flatfish, is functionally active in vertebrate cells.

    PubMed

    Clark, Karl J; Carlson, Daniel F; Leaver, Michael J; Foster, Linda K; Fahrenkrug, Scott C

    2009-03-01

    The Tc1/mariner family of DNA transposons is widespread across fungal, plant and animal kingdoms, and thought to contribute to the evolution of their host genomes. To date, an active Tc1 transposon has not been identified within the native genome of a vertebrate. We demonstrate that Passport, a native transposon isolated from a fish (Pleuronectes platessa), is active in a variety of vertebrate cells. In transposition assays, we found that the Passport transposon system improved stable cellular transgenesis by 40-fold, has an apparent preference for insertion into genes, and is subject to overproduction inhibition like other Tc1 elements. Passport represents the first vertebrate Tc1 element described as both natively intact and functionally active, and given its restricted phylogenetic distribution, may be contemporaneously active. The Passport transposon system thus complements the available genetic tools for the manipulation of vertebrate genomes, and may provide a unique system for studying the infiltration of vertebrate genomes by Tc1 elements.

  14. Screening of active metals for reactive adsorption desulfurization adsorbent using density functional theory

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Zhao, Liang; Xu, Chunming; Wang, Yuxian; Gao, Jinsen

    2017-03-01

    To explore characteristics of active metals for reactive adsorption desulfurization (RADS) technology, the adsorption of thiophene on M (100) (M = Cr, Mo, Co, Ni, Cu, Au, and Ag) surfaces was systematically studied by density functional theory with vdW correction (DFT + D3). We found that, in all case, the most stable molecular adsorption site was the hollow site and adsorptive capabilities of thiophene followed the order: Cr > Mo > Co ≈ Ni > Cu > Au ≈ Ag. By analyzing the nature of binding between thiophene and corresponding metals and the electronic structure of metals, the excessive activities of Cr and Mo were found to have a negative regeneration, the passive activities of Au and Ag were found to have an inactive adsorption for RADS adsorbent alone, while Ni and Co have appropriate characteristics as the active metals for RADS, followed by Cu.

  15. The oxidase activity of vascular adhesion protein-1 (VAP-1) is essential for function.

    PubMed

    Noonan, Thomas; Lukas, Susan; Peet, Gregory W; Pelletier, Josephine; Panzenbeck, Mark; Hanidu, Adedayo; Mazurek, Suzanne; Wasti, Ruby; Rybina, Irina; Roma, Teresa; Kronkaitis, Anthony; Shoultz, Alycia; Souza, Donald; Jiang, Huiping; Nabozny, Gerald; Modis, Louise Kelly

    2013-01-01

    Vascular adhesion protein-1 (VAP-1) has been implicated in the pathogenesis of inflammatory diseases and is suggested to play a role in immune cell trafficking. It is not clear whether this effect is mediated by the oxidase activity or by other features of the protein such as direct adhesion. In order to study the role of VAP-1 oxidase activity in vivo, we have generated mice carrying an oxidase activity-null VAP-1 protein. We demonstrate that the VAP-1 oxidase null mutant mice have a phenotype similar to the VAP-1 null mice in animal models of sterile peritonitis and antibody induced arthritis suggesting that the oxidase activity is responsible for the inflammatory function of VAP-1.

  16. The oxidase activity of vascular adhesion protein-1 (VAP-1) is essential for function

    PubMed Central

    Noonan, Thomas; Lukas, Susan; Peet, Gregory W; Pelletier, Josephine; Panzenbeck, Mark; Hanidu, Adedayo; Mazurek, Suzanne; Wasti, Ruby; Rybina, Irina; Roma, Teresa; Kronkaitis, Anthony; Shoultz, Alycia; Souza, Donald; Jiang, Huiping; Nabozny, Gerald; Modis, Louise Kelly

    2013-01-01

    Vascular adhesion protein-1 (VAP-1) has been implicated in the pathogenesis of inflammatory diseases and is suggested to play a role in immune cell trafficking. It is not clear whether this effect is mediated by the oxidase activity or by other features of the protein such as direct adhesion. In order to study the role of VAP-1 oxidase activity in vivo, we have generated mice carrying an oxidase activity-null VAP-1 protein. We demonstrate that the VAP-1 oxidase null mutant mice have a phenotype similar to the VAP-1 null mice in animal models of sterile peritonitis and antibody induced arthritis suggesting that the oxidase activity is responsible for the inflammatory function of VAP-1. PMID:23885334

  17. Structure-Functional Study of Tyrosine and Methionine Dipeptides: An Approach to Antioxidant Activity Prediction

    PubMed Central

    Torkova, Anna; Koroleva, Olga; Khrameeva, Ekaterina; Fedorova, Tatyana; Tsentalovich, Mikhail

    2015-01-01

    Quantum chemical methods allow screening and prediction of peptide antioxidant activity on the basis of known experimental data. It can be used to design the selective proteolysis of protein sources in order to obtain products with antioxidant activity. Molecular geometry and electronic descriptors of redox-active amino acids, as well as tyrosine and methionine-containing dipeptides, were studied by Density Functional Theory method. The calculated data was used to reveal several descriptors responsible for the antioxidant capacities of the model compounds based on their experimentally obtained antioxidant capacities against ABTS (2,2′-Azino-bis-(3-ethyl-benzothiazoline-6-sulfonate)) and peroxyl radical. A formula to predict antioxidant activity of peptides was proposed. PMID:26512651

  18. Function and regulation of large conductance Ca(2+)-activated K+ channel in vascular smooth muscle cells.

    PubMed

    Hu, Xiang-Qun; Zhang, Lubo

    2012-09-01

    Large conductance Ca(2+)-activated K(+) (BK(Ca)) channels are abundantly expressed in vascular smooth muscle cells. Activation of BK(Ca) channels leads to hyperpolarization of cell membrane, which in turn counteracts vasoconstriction. Therefore, BK(Ca) channels have an important role in regulation of vascular tone and blood pressure. The activity of BK(Ca) channels is subject to modulation by various factors. Furthermore, the function of BK(Ca) channels are altered in both physiological and pathophysiological conditions, such as pregnancy, hypertension and diabetes, which has dramatic impacts on vascular tone and hemodynamics. Consequently, compounds and genetic manipulation that alter activity and expression of the channel might be of therapeutic interest.

  19. Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function

    PubMed Central

    Muhammad, Karzan; Reddy-Alla, Suneel; Driller, Jan H; Schreiner, Dietmar; Rey, Ulises; Böhme, Mathias A.; Hollmann, Christina; Ramesh, Niraja; Depner, Harald; Lützkendorf, Janine; Matkovic, Tanja; Götz, Torsten; Bergeron, Dominique D.; Schmoranzer, Jan; Goettfert, Fabian; Holt, Mathew; Wahl, Markus C.; Hell, Stefan W.; Scheiffele, Peter; Walter, Alexander M.; Loll, Bernhard; Sigrist, Stephan J.

    2015-01-01

    Assembly and maturation of synapses at the Drosophila neuromuscular junction (NMJ) depend on trans-synaptic neurexin/neuroligin signalling, which is promoted by the scaffolding protein Syd-1 binding to neurexin. Here we report that the scaffold protein spinophilin binds to the C-terminal portion of neurexin and is needed to limit neurexin/neuroligin signalling by acting antagonistic to Syd-1. Loss of presynaptic spinophilin results in the formation of excess, but atypically small active zones. Neuroligin-1/neurexin-1/Syd-1 levels are increased at spinophilin mutant NMJs, and removal of single copies of the neurexin-1, Syd-1 or neuroligin-1 genes suppresses the spinophilin-active zone phenotype. Evoked transmission is strongly reduced at spinophilin terminals, owing to a severely reduced release probability at individual active zones. We conclude that presynaptic spinophilin fine-tunes neurexin/neuroligin signalling to control active zone number and functionality, thereby optimizing them for action potential-induced exocytosis. PMID:26471740

  20. Enhanced Activity and Stability of Pt catalysts on Functionalized Graphene Sheets for Electrocatalytic Oxygen Reduction

    SciTech Connect

    Kou, Rong; Shao, Yuyan; Wang, Donghai; Engelhard, Mark H.; Kwak, Ja Hun; Wang, Jun; Viswanathan, Vilayanur V.; Wang, Chong M.; Lin, Yuehe; Wang, Yong; Aksay, Ilhan A.; Liu, Jun

    2009-04-30

    Electrocatalysis of oxygen reduction using Pt nanoparticles supported on functionalized graphene sheets (FGSs) was studied. FGSs were prepared by thermal expansion of graphite oxide. Pt nanoparticles with average diameter of 2 nm were uniformly loaded on FGSs by impregnation methods. Pt-FGS showed a higher electrochemical surface area and oxygen reduction activity with improved stability as compared with commercial catalyst. Transmission electron microscopy, X-ray photoelectron spectroscopy, and electrochemical characterization suggest that the improved performance of Pt-FGS can be attributed to smaller particle size and less aggregation of Pt nanoparticles on the functionalized graphene sheets.

  1. Electronic assessment of disease activity and functioning in patients with axial spondyloarthritis: challenges and unmet needs.

    PubMed

    Kiltz, Uta; Boonen, Annelies; Braun, Juergen; Richter, Jutta G

    2016-01-01

    The dynamic clinical course of rheumatic conditions indicates a need for regular collection of information on health status to monitor disease activity and functional status. Patient-reported outcomes measures (PROMs) are playing a key role in the evaluation of symptoms and functioning and health, and are crucial in the initiation of treatment in those patients. In recent years, electronic assessments of PROMs (so called ePROMs) have been introduced. This report summarises some of the rationale, opportunities, and results using ePROMs in patients with spondyloarthritis (SpA).

  2. The daily life of elderly Germans: activity patterns, personal control, and functional health.

    PubMed

    Baltes, M M; Wahl, H W; Schmid-Furstoss, U

    1990-07-01

    Aging processes are often described as an interacting system of personal and environmental conditions. It is surprising, therefore, to find an almost complete lack of reliable data describing the everyday lives of the elderly in terms of external components such as type of activities, locations, and companionship. The present study is an attempt to remedy this lack of information and thereby provide a basis for a better understanding of aging processes. Forty-nine mobile and independently living elderly people (mean age = 72.7) recorded their daily activities over a period of 6 months. During a randomly selected week per month they kept a prestructured diary about what activities they engaged in, where, when, and with whom. In addition, functional health and personal control beliefs were assessed. The diaries were coded along 37 activity categories (inter-rater reliability estimated via Cohen's Kappa: M = .93), 5 categories for location and 6 categories for companionship. The major findings can be summarized as follows: The typical activity profile is characterized, in terms of highest frequency, by obligatory activities. In terms of time, however, they make up but little more than half of the day, predominantly the mornings. Afternoons and evenings, were mostly spent with leisure activities. The paths of daily lives of the elderly were marked by two geographic domains. The first and foremost is the home, followed by public places. With regard to the relationship between activities and personal control, we find a close relationship particularly when functional health is low.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Physical activity, functional capacity, and step variability during walking in people with lower-limb amputation.

    PubMed

    Lin, Suh-Jen; Winston, Katie D; Mitchell, Jill; Girlinghouse, Jacob; Crochet, Karleigh

    2014-01-01

    Physical activity is important for general health. For an individual with amputation to sustain physical activity, certain functional capacity might be needed. Gait variability is related to the incidence of falls. This study explored the relationship between physical activity and a few common performance measures (six-minute walk test, step length variability, step width variability, and comfortable walking speed) in individuals with unilateral lower-limb amputation. Twenty individuals completed the study (age: 50±11yrs). Twelve of them had transtibial amputation, seven had transfemoral amputation, and one had through-knee amputation. Gait data was collected by the GaitRite instrumented walkway while participants performed a 3-min comfortable walking trial followed by a six-minute walk test. Physical activity was indicated by the mean of 7-day step counts via a pedometer. Gait variability was calculated by the coefficient of variation. Pearson correlation analysis was conducted between physical activity level and the 4 performance measures. Significance level was set at 0.05. Physical activity correlates strongly to comfortable walking speed (r=0.76), six-minute walk distance (r=0.67), and correlates fairly to step width variability (r=0.44). On the contrary, physical activity is inversely related to step length variability of the prosthetic leg (r=-0.46) and of the sound leg (r=-0.47). Having better functional capacity and lateral stability might enable an individual with lower-limb amputation to engage in a higher physical activity level, or vise versa. However, our conclusions are only preliminary as limited by the small sample size.

  4. Associations of Monitor-Assessed Activity with Performance-Based Physical Function

    PubMed Central

    Reid, Natasha; Daly, Robin M.; Winkler, Elisabeth A. H.; Gardiner, Paul A.; Eakin, Elizabeth G.; Owen, Neville; Dunstan, David W.; Healy, Genevieve N.

    2016-01-01

    The purpose of this study was to investigate the cross-sectional associations of monitor-derived measures of sedentary time and physical activity with performance-based physical function in healthy Australian adults. Data from 602 participants (mean age 58.1±10.0 years; 58% female) from the 2011/12 wave of the Australian Diabetes, Obesity and Lifestyle (AusDiab3) study were analyzed. The thigh-worn activPAL3™ monitor (7-days continuous wear) was used to derive time during waking hours spent: sitting/reclining; standing; and, stepping (overall, and separately as light [<3 METs] and moderate-to-vigorous physical activity [MVPA; ≥3 METs]), and number of sit-stand transitions. Associations of these (in hours/day, or 15 transitions/day) with physical function measures (8ft Timed Up and Go [TUG-8; log-transformed seconds] and Knee Extensor Strength [KES; kg]) were tested via linear regression, adjusting for confounders. Interactions by sex and age-category (<45; 45–54; 55–64; ≥65 years) were tested. In all participants, KES was significantly (p<0.05) associated with stepping and MVPA stepping only; none of the activity measures were associated with TUG-8. However, subgroup analysis revealed that in older adults (≥65 years), TUG-8 was associated with stepping and MVPA stepping (both p<0.05). All associations with sitting time, standing, sit-stand transition and sex interactions were not statistically significant. In summary, sitting time was not significantly associated with impaired muscle strength or gait/mobility in Australian adults aged 36–80 years, but light- to moderate activity (stepping) was positively associated with muscle strength, and gait/mobility in older adults aged ≥65 years. The direction of causation is not known and remains important to investigate considering the high prevalence of both poor function and limited activity in older age. PMID:27073888

  5. Functional differences between junctional and extrajunctional adrenergic receptor activation in mammalian ventricle

    PubMed Central

    Ajijola, Olujimi A.; Vaseghi, Marmar; Zhou, Wei; Yamakawa, Kentaro; Benharash, Peyman; Hadaya, Joseph; Lux, Robert L.; Mahajan, Aman

    2013-01-01

    Increased cardiac sympathetic activation worsens dispersion of repolarization and is proarrhythmic. The functional differences between intrinsic nerve stimulation and adrenergic receptor activation remain incompletely understood. This study was undertaken to determine the functional differences between efferent cardiac sympathetic nerve stimulation and direct adrenergic receptor activation in porcine ventricles. Female Yorkshire pigs (n = 13) underwent surgical exposure of the heart and stellate ganglia. A 56-electrode sock was placed over the ventricles to record epicardial electrograms. Animals underwent bilateral sympathetic stimulation (BSS) (n = 8) or norepinephrine (NE) administration (n = 5). Activation recovery intervals (ARIs) were measured at each electrode before and during BSS or NE. The degree of ARI shortening during BSS or NE administration was used as a measure of functional nerve or adrenergic receptor density. During BSS, ARI shortening was nonuniform across the epicardium (F value 9.62, P = 0.003), with ARI shortening greatest in the mid-basal lateral right ventricle and least in the midposterior left ventricle (LV) (mean normalized values: 0.9 ± 0.08 vs. 0.56 ± 0.08; P = 0.03). NE administration resulted in greater ARI shortening in the LV apex than basal segments [0.91 ± 0.04 vs. 0.63 ± 0.05 (averaged basal segments); P = 0.003]. Dispersion of ARIs increased in 50% and 60% of the subjects undergoing BSS and NE, respectively, but decreased in the others. There is nonuniform response to cardiac sympathetic activation of both porcine ventricles, which is not fully explained by adrenergic receptor density. Different pools of adrenergic receptors may mediate the cardiac electrophysiological effects of efferent sympathetic nerve activity and circulating catecholamines. PMID:23241324

  6. Functional measures developed for clinical populations identified impairment among active workers with upper extremity disorders

    PubMed Central

    Gardner, Bethany T.; Dale, Ann Marie; Buckner-Petty, Skye; Rachford, Robert; Strickland, Jaime; Kaskutas, Vicki; Evanoff, Bradley

    2017-01-01

    Purpose Few studies have explored measures of function across a range of health outcomes in a general working population. Using four upper extremity (UE) case definitions from the scientific literature, we described the performance of functional measures of work, activities of daily living, and overall health. Methods A sample of 573 workers completed several functional measures: modified recall versions of the QuickDASH, Levine Functional Status Scale (FSS), DASH Work module (DASH-W), and standard SF-8 physical component score. We determined case status based on four UE case definitions: 1) UE symptoms, 2) UE musculoskeletal disorders (MSD), 3) carpal tunnel syndrome (CTS), and 4) work limitations due to UE symptoms. We calculated effect sizes for each case definition to show the magnitude of the differences that were detected between cases and non-cases for each case definition on each functional measure. Sensitivity and specificity analyses showed how well each measure identified functional impairments across the UE case definitions. Results All measures discriminated between cases and non-cases for each case definition with the largest effect sizes for CTS and work limitations, particularly for the modified FSS and DASH-W measures. Specificity was high and sensitivity was low for outcomes of UE symptoms and UE MSD in all measures. Sensitivity was high for CTS and work limitations. Conclusions Functional measures developed specifically for use in clinical, treatment-seeking populations may identify mild levels of impairment in relatively healthy, active working populations, but measures performed better among workers with CTS or those reporting limitations at work. PMID:26091980

  7. A density functional theory model of mechanically activated silyl ester hydrolysis

    SciTech Connect

    Pill, Michael F.; Schmidt, Sebastian W.; Beyer, Martin K.; Clausen-Schaumann, Hauke; Kersch, Alfred

    2014-01-28

    To elucidate the mechanism of the mechanically activated dissociation of chemical bonds between carboxymethylated amylose (CMA) and silane functionalized silicon dioxide, we have investigated the dissociation kinetics of the bonds connecting CMA to silicon oxide surfaces with density functional calculations including the effects of force, solvent polarizability, and pH. We have determined the activation energies, the pre-exponential factors, and the reaction rate constants of candidate reactions. The weakest bond was found to be the silyl ester bond between the silicon and the alkoxy oxygen atom. Under acidic conditions, spontaneous proton addition occurs close to the silyl ester such that neutral reactions become insignificant. Upon proton addition at the most favored position, the activation energy for bond hydrolysis becomes 31 kJ mol{sup −1}, which agrees very well with experimental observation. Heterolytic bond scission in the protonated molecule has a much higher activation energy. The experimentally observed bi-exponential rupture kinetics can be explained by different side groups attached to the silicon atom of the silyl ester. The fact that different side groups lead to different dissociation kinetics provides an opportunity to deliberately modify and tune the kinetic parameters of mechanically activated bond dissociation of silyl esters.

  8. Functional Diversity and Microbial Activity of Forest Soils that Are Heavily Contaminated by Lead and Zinc.

    PubMed

    Pająk, Marek; Błońska, Ewa; Frąc, Magdalena; Oszust, Karolina

    The objective of this study was to assess the impact of metal contamination on microbial functional diversity and enzyme activity in forest soils. This study involved the evaluation of the influence of the texture, carbon content and distance to the source of contamination on the change in soil microbial activity, which did not investigate in previous studies. The study area is located in southern Poland near the city of Olkusz around the flotation sedimentation pond of lead and zinc at the Mining and Metallurgical Company "ZGH Bolesław, Inc.". The central point of the study area was selected as the middle part of the sedimentation pond. The experiment was conducted over a regular 500 × 500-m grid, where 33 sampling points were established. Contents of organic carbon and trace elements (Zn, Pb and Cd), pH and soil texture were investigated. The study included the determination of dehydrogenase and urease activities and microbial functional diversity evaluation based on the community-level physiological profiling approach by Biolog EcoPlate. The greatest reduction in the dehydrogenase and urease activities was observed in light sandy soils with Zn content >220 mg · kg(-1) and a Pb content > 100 mg · kg(-1). Soils with a higher concentration of fine fraction, despite having the greatest concentrations of metals, were characterized by high rates of Biolog®-derived parameters and a lower reduction of enzyme activity.

  9. Osteoinductive activity of insulin-functionalized cell culture surfaces obtained using diazonium chemistry

    NASA Astrophysics Data System (ADS)

    Mikulska, Anna; Filipowska, Joanna; Osyczka, Anna; Nowakowska, Maria; Szczubiałka, Krzysztof

    2014-12-01

    Polymeric surfaces suitable for cell culture (DR/Pec) were constructed from diazoresin (DR) and pectin (Pec) in a form of ultrathin films using the layer-by-layer (LbL) technique. The surfaces were functionalized with insulin using diazonium chemistry. Such functionalized surfaces were used to culture human mesenchymal stem cells (hMSCs) to assess their suitability for bone tissue engineering and regeneration. The activity of insulin immobilized on the surfaces (DR/Pec/Ins) was compared to that of insulin dissolved in the culture medium. Human MSC grown on insulin-immobilized DR/Pec surfaces displayed increased proliferation and higher osteogenic activity. The latter was determined by means of alkaline phosphatase (ALP) activity, which increases at early stages of osteoblasts differentiation. Insulin dissolved in the culture medium did not stimulate cell proliferation and its osteogenic activity was significantly lower. Addition of recombinant human bone morphogenetic protein 2 (rhBMP-2) to the culture medium further increased ALP activity in hMSCs indicating additive osteogenic action of immobilized insulin and rhBMP-2

  10. AMP-activated protein kinase—an energy sensor that regulates all aspects of cell function

    PubMed Central

    Hardie, D. Grahame

    2011-01-01

    AMP-activated protein kinase (AMPK) is a sensor of energy status that maintains cellular energy homeostasis. It arose very early during eukaryotic evolution, and its ancestral role may have been in the response to starvation. Recent work shows that the kinase is activated by increases not only in AMP, but also in ADP. Although best known for its effects on metabolism, AMPK has many other functions, including regulation of mitochondrial biogenesis and disposal, autophagy, cell polarity, and cell growth and proliferation. Both tumor cells and viruses establish mechanisms to down-regulate AMPK, allowing them to escape its restraining influences on growth. PMID:21937710

  11. Functional Modularity of Background Activities in Normal and Epileptic Brain Networks

    NASA Astrophysics Data System (ADS)

    Chavez, M.; Valencia, M.; Navarro, V.; Latora, V.; Martinerie, J.

    2010-03-01

    We analyze the connectivity structure of weighted brain networks extracted from spontaneous magnetoencephalographic signals of healthy subjects and epileptic patients (suffering from absence seizures) recorded at rest. We find that, for the activities in the 5-14 Hz range, healthy brains exhibit a sparse connectivity, whereas the brain networks of patients display a rich connectivity with a clear modular structure. Our results suggest that modularity plays a key role in the functional organization of brain areas during normal and pathological neural activities at rest.

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

    PubMed

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

    2014-05-05

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

  13. Genetic and pharmacological evidence that a retinoic acid cannot be the RXR-activating ligand in mouse epidermis keratinocytes

    PubMed Central

    Calléja, Cécile; Messaddeq, Nadia; Chapellier, Benoit; Yang, Haiyuan; Krezel, Wojciech; Li, Mei; Metzger, Daniel; Mascrez, Bénédicte; Ohta, Kiminori; Kagechika, Hiroyuki; Endo, Yasuyuki; Mark, Manuel; Ghyselinck, Norbert B.; Chambon, Pierre

    2006-01-01

    Using genetic and pharmacological approaches, we demonstrate that both RARγ/RXRα heterodimers involved in repression events, as well as PPARβ(δ)/RXRα heterodimers involved in activation events, are cell-autonomously required in suprabasal keratinocytes for the generation of lamellar granules (LG), the organelles instrumental to the formation of the skin permeability barrier. In activating PPARβ(δ)/RXRα heterodimers, RXRα is transcriptionally active as its AF-2 activation function is required and can be inhibited by an RXR-selective antagonist. Within repressing RARγ/RXRα heterodimers, induction of the transcriptional activity of RXRα is subordinated to the addition of an agonistic ligand for RARγ. Thus, the ligand that possibly binds and activates RXRα heterodimerized with PPARβ(δ) cannot be a retinoic acid, as it would also bind RARγ and relieve the RARγ-mediated repression, thereby yielding abnormal LGs. Our data also demonstrate for the first time that subordination of RXR transcriptional activity to that of its RAR partner plays a crucial role in vivo, because it allows RXRs to act concomitantly, within the same cell, as heterodimerization partners for repression, as well as for activation events in which they are transcriptionally active. PMID:16751185

  14. Cyber Electromagnetic Activities within the Mission Command Warfighting Function: Why is it Important and What is the Capability?

    DTIC Science & Technology

    2013-12-13

    33 CEMA and the Mission Command Warfighting Function...Army Doctrine Publication ADRP Army Doctrine Reference Publication CEMA Cyber-Electromagnetic Activities DOD Department of Defense EMSO Electronic

  15. The Peroxisome Proliferator Activated Receptor‐γ Pioglitazone Improves Vascular Function and Decreases Disease Activity in Patients With Rheumatoid Arthritis

    PubMed Central

    Marder, Wendy; Khalatbari, Shokoufeh; Myles, James D.; Hench, Rita; Lustig, Susan; Yalavarthi, Srilakshmi; Parameswaran, Aishwarya; Brook, Robert D.; Kaplan, Mariana J.

    2013-01-01

    Background Rheumatoid arthritis (RA) is associated with heightened mortality due to atherosclerotic cardiovascular disease (CVD). Inflammatory pathways in RA negatively affect vascular physiology and promote metabolic disturbances that contribute to CVD. We hypothesized that the peroxisome proliferator activated receptor‐γ (PPAR‐γ) pioglitazone could promote potent vasculoprotective and anti‐inflammatory effects in RA. Methods and Results One hundred forty‐three non‐diabetic adult RA patients (76.2% female, age 55.2±12.1 [mean±SD]) on stable RA standard of care treatment were enrolled in a randomized, double‐blind placebo controlled crossover trial of 45 mg daily pioglitazone versus placebo, with a 3‐month duration/arm and a 2‐month washout period. Pulse wave velocity of the aorta (PWV), brachial artery flow mediated dilatation (FMD), nitroglycerin mediated dilatation (NMD), microvascular endothelial function (reactive hyperemia index [RHI]), and circulating biomarkers of inflammation, insulin resistance, and atherosclerosis risk all were quantified. RA disease activity was assessed with the 28‐Joint Count Disease Activity Score (DAS‐28) C‐reactive protein (CRP) and the Short Form (36) Health Survey quality of life questionnaire. When added to standard of care RA treatment, pioglitazone significantly decreased pulse wave velocity (ie, aortic stiffness) (P=0.01), while FMD and RHI remained unchanged when compared to treatment with placebo. Further, pioglitazone significantly reduced RA disease activity (P=0.02) and CRP levels (P=0.001), while improving lipid profiles. The drug was well tolerated. Conclusions Addition of pioglitazone to RA standard of care significantly improves aortic elasticity and decreases inflammation and disease activity with minimal safety issues. The clinical implications of these findings remain to be established. Clinical Trial Registration URL: ClinicalTrials.gov Unique Identifier: NCT00554853. PMID:24252844

  16. Functional Reconstitution and Channel Activity Measurements of Purified Wildtype and Mutant CFTR Protein

    PubMed Central

    Eckford, Paul D. W.; Li, Canhui; Bear, Christine E.

    2015-01-01

    The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a unique channel-forming member of the ATP Binding Cassette (ABC) superfamily of transporters. The phosphorylation and nucleotide dependent chloride channel activity of CFTR has been frequently studied in whole cell systems and as single channels in excised membrane patches. Many Cystic Fibrosis-causing mutations have been shown to alter this activity. While a small number of purification protocols have been published, a fast reconstitution method that retains channel activity and a suitable method for studying population channel activity in a purified system have been lacking. Here rapid methods are described for purification and functional reconstitution of the full-length CFTR protein into proteoliposomes of defined lipid composition that retains activity as a regulated halide channel. This reconstitution method together with a novel flux-based assay of channel activity is a suitable system for studying the population channel properties of wild type CFTR and the disease-causing mutants F508del- and G551D-CFTR. Specifically, the method has utility in studying the direct effects of phosphorylation, nucleotides and small molecules such as potentiators and inhibitors on CFTR channel activity. The methods are also amenable to the study of other membrane channels/transporters for anionic substrates. PMID:25867140

  17. DCC functions as an accelerator of thalamocortical axonal growth downstream of spontaneous thalamic activity

    PubMed Central

    Castillo-Paterna, Mar; Moreno-Juan, Verónica; Filipchuk, Anton; Rodríguez-Malmierca, Luis; Susín, Rafael; López-Bendito, Guillermina

    2015-01-01

    Controlling the axon growth rate is fundamental when establishing brain connections. Using the thalamocortical system as a model, we previously showed that spontaneous calcium activity influences the growth rate of thalamocortical axons by regulating the transcription of Robo1 through an NF-κB-binding site in its promoter. Robo1 acts as a brake on the growth of thalamocortical axons in vivo. Here, we have identified the Netrin-1 receptor DCC as an accelerator for thalamic axon growth. Dcc transcription is regulated by spontaneous calcium activity in thalamocortical neurons and activating DCC signaling restores normal axon growth in electrically silenced neurons. Moreover, we identified an AP-1-binding site in the Dcc promoter that is crucial for the activity-dependent regulation of this gene. In summary, we have identified the Dcc gene as a novel downstream target of spontaneous calcium activity involved in axon growth. Together with our previous data, we demonstrate a mechanism to control axon growth that relies on the activity-dependent regulation of two functionally opposed receptors, Robo1 and DCC. These two proteins establish a tight and efficient means to regulate activity-guided axon growth in order to correctly establish neuronal connections during development. PMID:25947198

  18. Lysine Specific Demethylase 1 has Dual Functions as a Major Regulator of Androgen Receptor Transcriptional Activity

    PubMed Central

    Cai, Changmeng; He, Housheng Hansen; Gao, Shuai; Chen, Sen; Yu, Ziyang; Gao, Yanfei; Chen, Shaoyong; Chen, Mei Wei; Zhang, Jesse; Ahmed, Musaddeque; Wang, Yang; Metzger, Eric; Schüle, Roland; Liu, X. Shirley; Brown, Myles; Balk, Steven P.

    2014-01-01

    SUMMARY Lysine Specific Demethylase 1 (LSD1, KDM1A) functions as a transcriptional corepressor through demethylation of histone 3 lysine 4 (H3K4), but has coactivator function on some genes through unclear mechanisms. We show that LSD1, interacting with CoREST, associates with and coactivates androgen receptor (AR) on a large fraction of androgen-stimulated genes. A subset of these AR/LSD1-associated enhancer sites have histone 3 threonine 6 phosphorylation (H3T6ph), and these sites are further enriched for androgen-stimulated genes. Significantly, despite its coactivator activity, LSD1 still mediates H3K4me2 demethylation at these androgen-stimulated enhancers. FOXA1 is also associated with LSD1 at AR regulated enhancer sites, and a FOXA1 interaction with LSD1 enhances binding of both proteins at these sites. These findings show LSD1 functions broadly as a regulator of AR function, that it maintains a transcriptional repression function at AR-regulated enhancers through H3K4 demethylation, and has a distinct AR-linked coactivator function mediated by demethylation of other substrates. PMID:25482560

  19. Functional determinants of ras interference 1 mutants required for their inhbitory activity on endocytosis

    SciTech Connect

    Galvis, Adriana; Giambini, Hugo; Villasana, Zoilmar; Barbieri, M. Alejandro

    2009-03-10

    In this study, we initiated experiments to address the structure-function relationship of Rin1. A total of ten substitute mutations were created, and their effects on Rin1 function were examined. Of the ten mutants, four of them (P541A, E574A, Y577F, T580A) were defective in Rab5 binding, while two other Rin1 mutants (D537A, Y561F) partially interacted with Rab5. Mutations in several other residues (Y506F, Y523F, T572A, Y578F) resulted in partial loss of Rab5 function. Biochemical studies showed that six of them (D537A, P541A, Y561F, E574A, Y577F, T580A) were unable to activate Rab5 in an in vitro assay. In addition, Rin1: D537A and Rin1: Y561F mutants showed dominant inhibition of Rab5 function. Consistent with the biochemical studies, we observed that these two Rin1 mutants have lost their ability to stimulate the endocytosis of EGF, form enlarged Rab5-positive endosomes, or support in vitro endosome fusion. Based on these data, our results showed that mutations in the Vps9 domain of Rin1 lead to a loss-of-function phenotype, indicating a specific structure-function relationship between Rab5 and Rin1.

  20. Functional activation studies of word processing in the recovery from aphasia.

    PubMed

    Zahn, Roland; Schwarz, Michael; Huber, Walter

    2006-06-01

    Some reviews on theories of recovery in aphasia put an emphasis on neural network models based on empirical data from evoked-potentials in aphasia as an approach to mapping recovery of cognitive function to neural structure. We will focus here on what we call an "anatomical" approach to look at recovery in aphasia. "Anatomical" theories of recovery stated by classical aphasiologists have contributed to the understanding of language representations in the human brain. But many aspects of these theories can only be investigated by using modern techniques of lesion analysis, psychometric assessment and functional imaging. Whereas structure-function relations have been primarily established by looking for the association of deficit symptoms with certain lesions, functional activation methods offer a means to study more directly the functional anatomy of recovered or retained functions in neuropsychological patients. To falsify or build up anatomical theories of recovery we will propose a stepwise approach of inference. The methodological pitfalls of this approach will be discussed by focussing on anatomical hypotheses of semantic word comprehension and its impairment and recovery in aphasia.

  1. Effects of soil type and farm management on soil ecological functional genes and microbial activities

    SciTech Connect

    Reeve, Jennifer; Schadt, Christopher Warren; Carpenter-Boggs, Lynne; Kang, S.; Zhou, Jizhong; Reganold, John P.

    2010-01-01

    Relationships between soil microbial diversity and soil function are the subject of much debate. Process-level analyses have shown that microbial function varies with soil type and responds to soil management. However, such measurements cannot determine the role of community structure and diversity in soil function. The goal of this study was to investigate the role of gene frequency and diversity, measured by microarray analysis, on soil processes. The study was conducted in an agro-ecosystem characterized by contrasting management practices and soil types. Eight pairs of adjacent commercial organic and conventional strawberry fields were matched for soil type, strawberry variety, and all other environmental conditions. Soil physical, chemical and biological analyses were conducted including functional gene microarrays (FGA). Soil physical and chemical characteristics were primarily determined by soil textural type (coarse vs fine-textured), but biological and FGA measures were more influenced by management (organic vs conventional). Organically managed soils consistently showed greater functional activity as well as FGA signal intensity (SI) and diversity. Overall FGA SI and diversity were correlated to total soil microbial biomass. Functional gene group SI and/or diversity were correlated to related soil chemical and biological measures such as microbial biomass, cellulose, dehydrogenase, ammonium and sulfur. Management was the dominant determinant of soil biology as measured by microbial gene frequency and diversity, which paralleled measured microbial processes.

  2. ALD Functionalized Nanoporous Gold: Thermal Stability, Mechanical Properties, and Catalytic Activity

    SciTech Connect

    Biener, M M; Biener, J; Wichmann, A; Wittstock, A; Baumann, T F; Baeumer, M; Hamza, A V

    2011-03-24

    Nanoporous metals have many technologically promising applications but their tendency to coarsen limits their long-term stability and excludes high temperature applications. Here, we demonstrate that atomic layer deposition (ALD) can be used to stabilize and functionalize nanoporous metals. Specifically, we studied the effect of nanometer-thick alumina and titania ALD films on thermal stability, mechanical properties, and catalytic activity of nanoporous gold (np-Au). Our results demonstrate that even only one-nm-thick oxide films can stabilize the nanoscale morphology of np-Au up to 1000 C, while simultaneously making the material stronger and stiffer. The catalytic activity of np-Au can be drastically increased by TiO{sub 2} ALD coatings. Our results open the door to high temperature sensor, actuator, and catalysis applications and functionalized electrodes for energy storage and harvesting applications.

  3. Optimization of polysaccharides extraction from watermelon rinds: Structure, functional and biological activities.

    PubMed

    Romdhane, Molka Ben; Haddar, Anissa; Ghazala, Imen; Jeddou, Khawla Ben; Helbert, Claire Boisset; Ellouz-Chaabouni, Semia

    2017-02-01

    In the present work, optimization of hot water extraction, structural characteristics, functional properties, and biological activities of polysaccharides extracted from watermelon rinds (WMRP) were investigated. The physicochemical characteristics and the monosaccharide composition of these polysaccharides were then determined using chemical composition analysis, Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and gas chromatography-flame ionization detection (GC-FID). SEM images showed that extracted polysaccharides had a rough surface with many cavities. GC-FID results proved that galactose was the dominant sugar in the extracted polysaccharides, followed by arabinose, glucose, galacturonic acid, rhamnose, mannose, xylose and traces of glucuronic acid. The findings revealed that WMRP displayed excellent antihypertensive and antioxidant activities. Those polysaccharides had also a protection effect against hydroxyl radical-induced DNA damage. Functional properties of extracted polysaccharides were also evaluated. WMRP showed good interfacial dose-dependent proprieties. Overall, the results suggested that WMRP presents a promising natural source of antioxidants and antihypertensive agents.

  4. Structural Waters Define a Functional Channel Mediating Activation of the GPCR, rhodopsin

    SciTech Connect

    Angel, T.; Gupta, S; Jastrzebska, B; Palczewski, K; Chance, M

    2009-01-01

    Structural water molecules may act as prosthetic groups indispensable for proper protein function. In the case of allosteric activation of G protein-coupled receptors (GPCRs), water likely imparts structural plasticity required for agonist-induced signal transmission. Inspection of structures of GPCR superfamily members reveals the presence of conserved embedded water molecules likely important to GPCR function. Coupling radiolytic hydroxyl radical labeling with rapid H2O18 solvent mixing, we observed no exchange of these structural waters with bulk solvent in either ground state or for the Meta II or opsin states. However, the radiolysis approach permitted labeling of selected side chain residues within the transmembrane helices and revealed activation-induced changes in local structural constraints likely mediated by dynamics of both water and protein. These results suggest both a possible general mechanism for water-dependent communication in family A GPCRs based on structural conservation, and a strategy for probing membrane protein structure.

  5. Ctk1 Function Is Necessary for Full Translation Initiation Activity in Saccharomyces cerevisiae

    PubMed Central

    Coordes, Britta; Brünger, Katharina M.; Burger, Kaspar; Soufi, Boumediene; Horenk, Juliane; Eick, Dirk; Olsen, Jesper V.

    2014-01-01

    Translation is a fundamental and highly regulated cellular process. Previously, we reported that the kinase and transcription elongation factor Ctk1 increases fidelity during translation elongation in Saccharomyces cerevisiae. Here, we show that loss of Ctk1 function also affects the initiation step of translation. Translation active extracts from Ctk1-depleted cells show impaired translation activity of capped mRNA, but not mRNA reporters containing the cricket paralysis virus (CrPV) internal ribosome entry site (IRES). Furthermore, the formation of 80S initiation complexes is decreased, which is probably due to reduced subunit joining. In addition, we determined the changes in the phosphorylation pattern of a ribosome enriched fraction after depletion of Ctk1. Thus, we provide a catalogue of phosphoproteomic changes dependent on Ctk1. Taken together, our data suggest a stimulatory function of Ctk1 in 80S formation during translation initiation. PMID:25416238

  6. Multistability of second-order competitive neural networks with nondecreasing saturated activation functions.

    PubMed

    Nie, Xiaobing; Cao, Jinde

    2011-11-01

    In this paper, second-order interactions are introduced into competitive neural networks (NNs) and the multistability is discussed for second-order competitive NNs (SOCNNs) with nondecreasing saturated activation functions. Firstly, based on decomposition of state space, Cauchy convergence principle, and inequality technique, some sufficient conditions ensuring the local exponential stability of 2N equilibrium points are derived. Secondly, some conditions are obtained for ascertaining equilibrium points to be locally exponentially stable and to be located in any designated region. Thirdly, the theory is extended to more general saturated activation functions with 2r corner points and a sufficient criterion is given under which the SOCNNs can have (r+1)N locally exponentially stable equilibrium points. Even if there is no second-order interactions, the obtained results are less restrictive than those in some recent works. Finally, three examples with their simulations are presented to verify the theoretical analysis.

  7. Functional mapping of protein kinase A reveals its importance in adult Schistosoma mansoni motor activity.

    PubMed

    de Saram, Paulu S R; Ressurreição, Margarida; Davies, Angela J; Rollinson, David; Emery, Aidan M; Walker, Anthony J

    2013-01-01

    Cyclic AMP (cAMP)-dependent protein kinase/protein kinase A (PKA) is the major transducer of cAMP signalling in eukaryotic cells. Here, using laser scanning confocal microscopy and 'smart' anti-phospho PKA antibodies that exclusively detect activated PKA, we provide a detailed in situ analysis of PKA signalling in intact adult Schistosoma mansoni, a causative agent of debilitating human intestinal schistosomiasis. In both adult male and female worms, activated PKA was consistently found associated with the tegument, oral and ventral suckers, oesophagus and somatic musculature. In addition, the seminal vesicle and gynaecophoric canal muscles of the male displayed activated PKA whereas in female worms activated PKA localized to the ootype wall, the ovary, and the uterus particularly around eggs during expulsion. Exposure of live worms to the PKA activator forskolin (50 µM) resulted in striking PKA activation in the central and peripheral nervous system including at nerve endings at/near the tegument surface. Such neuronal PKA activation was also observed without forskolin treatment, but only in a single batch of worms. In addition, PKA activation within the central and peripheral nervous systems visibly increased within 15 min of worm-pair separation when compared to that observed in closely coupled worm pairs. Finally, exposure of adult worms to forskolin induced hyperkinesias in a time and dose dependent manner with 100 µM forskolin significantly increasing the frequency of gross worm movements to 5.3 times that of control worms (P≤0.001). Collectively these data are consistent with PKA playing a central part in motor activity and neuronal communication, and possibly interplay between these two systems in S. mansoni. This study, the first to localize a protein kinase when exclusively in an activated state in adult S. mansoni, provides valuable insight into the intricacies of functional protein kinase signalling in the context of whole schistosome physiology.

  8. Metformin induces up-regulation of blood-brain barrier functions by activating AMP-activated protein kinase in rat brain microvascular endothelial cells.

    PubMed

    Takata, Fuyuko; Dohgu, Shinya; Matsumoto, Junichi; Machida, Takashi; Kaneshima, Shuji; Matsuo, Mai; Sakaguchi, Shinya; Takeshige, Yuki; Yamauchi, Atsushi; Kataoka, Yasufumi

    2013-04-19

    Blood-brain barrier (BBB) disruption occurs frequently in CNS diseases and injuries. Few drugs have been developed as therapeutic candidates for facilitating BBB functions. Here, we examined whether metformin up-regulates BBB functions using rat brain microvascular endothelial cells (RBECs). Metformin, concentration- and time-dependently increased transendothelial electrical resistance of RBEC monolayers, and decreased RBEC permeability to sodium fluorescein and Evans blue albumin. These effects of metformin were blocked by compound C, an inhibitor of AMP-activated protein kinase (AMPK). AMPK stimulation with an AMPK activator, AICAR, enhanced BBB functions. These findings indicate that metformin induces up-regulation of BBB functions via AMPK activation.

  9. Late-Stage Diversification of Biologically Active Molecules via Chemoenzymatic C-H Functionalization.

    PubMed

    Durak, Landon J; Payne, James T; Lewis, Jared C

    2016-03-04

    Engineered variants of rebeccamycin halogenase were used to selectively halogenate a number of biologically active aromatic compounds. Subsequent Pd-catalyzed cross-coupling reactions on the crude extracts of these reactions were used to install aryl, amine, and ether substituents at the halogenation site. This simple, chemoenzymatic method enables non-directed functionalization of C-H bonds on a range of substrates to provide access to derivatives that would be challenging or inefficient to prepare by other means.

  10. The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function

    PubMed Central

    Cai, Weili; Wei, Youheng; Jarnik, Michal; Reich, John; Lilly, Mary A.

    2016-01-01

    TORC1 is a master regulator of metabolism in eukaryotes that responds to multiple upstream signaling pathways. The GATOR complex is a newly defined upstream regulator of TORC1 that contains two sub-complexes, GATOR1, which inhibits TORC1 activity in response to amino acid starvation and GATOR2, which opposes the activity of GATOR1. While the GATOR1 complex has been implicated in a wide array of human pathologies including cancer and hereditary forms of epilepsy, the in vivo relevance of the GATOR2 complex remains poorly understood in metazoans. Here we define the in vivo role of the GATOR2 component Wdr24 in Drosophila. Using a combination of genetic, biochemical, and cell biological techniques we demonstrate that Wdr24 has both TORC1 dependent and independent functions in the regulation of cellular metabolism. Through the characterization of a null allele, we show that Wdr24 is a critical effector of the GATOR2 complex that promotes the robust activation of TORC1 and cellular growth in a broad array of Drosophila tissues. Additionally, epistasis analysis between wdr24 and genes that encode components of the GATOR1 complex revealed that Wdr24 has a second critical function, the TORC1 independent regulation of lysosome dynamics and autophagic flux. Notably, we find that two additional members of the GATOR2 complex, Mio and Seh1, also have a TORC1 independent role in the regulation of lysosome function. These findings represent a surprising and previously unrecognized function of GATOR2 complex components in the regulation of lysosomes. Consistent with our findings in Drosophila, through the characterization of a wdr24-/- knockout HeLa cell line we determined that Wdr24 promotes lysosome acidification and autophagic flux in mammalian cells. Taken together our data support the model that Wdr24 is a key effector of the GATOR2 complex, required for both TORC1 activation and the TORC1 independent regulation of lysosomes. PMID:27166823

  11. Effect of Citrocard on functional activity of cardiomyocyte mitochondria during chronic alcohol intoxication.

    PubMed

    Perfilova, V N; Ostrovskii, O V; Verovskii, V E; Popova, T A; Lebedeva, S A; Dib, H

    2007-03-01

    Chronic administration of 50% ethanol in a dose of 8 g/kg produces a toxic effect on functional activity of cardiomyocyte mitochondria, which manifested in decreased rates of respiration and oxidative phosphorylation. Structural GABA analogue Citrocard (phenibut citrate) and reference preparation piracetam in doses of 50 and 200 mg/kg, respectively, prevented the damaging effect of alcohol, which was seen from increased indexes of oxidative phosphorylation in treated animals compared to the control group.

  12. A generalized activating function for predicting virtual electrodes in cardiac tissue.

    PubMed Central

    Sobie, E A; Susil, R C; Tung, L

    1997-01-01

    To fully understand the mechanisms of defibrillation, it is critical to know how a given electrical stimulus causes membrane polarizations in cardiac tissue. We have extended the concept of the activating function, originally used to describe neuronal stimulation, to derive a new expression that identifies the sources that drive changes in transmembrane potential. Source terms, or virtual electrodes, consist of either second derivatives of extracellular potential weighted by intracellular conductivity or extracellular potential gradients weighted by derivatives of intracellular conductivity. The full response of passive tissue can be considered, in simple cases, to be a convolution of this "generalized activating function" with the impulse response of the tissue. Computer simulations of a two-dimensional sheet of passive myocardium under steady-state conditions demonstrate that this source term is useful for estimating the effects of applied electrical stimuli. The generalized activating function predicts oppositely polarized regions of tissue when unequally anisotropic tissue is point stimulated and a monopolar response when a point stimulus is applied to isotropic tissue. In the bulk of the myocardium, this new expression is helpful for understanding mechanisms by which virtual electrodes can be produced, such as the hypothetical "sawtooth" pattern of polarization, as well as polarization owing to regions of depressed conductivity, missing cells or clefts, changes in fiber diameter, or fiber curvature. In comparing solutions obtained with an assumed extracellular potential distribution to those with fully coupled intra- and extracellular domains, we find that the former provides a reliable estimate of the total solution. Thus the generalized activating function that we have derived provides a useful way of understanding virtual electrode effects in cardiac tissue. Images FIGURE 2 FIGURE 4 FIGURE 5 FIGURE 6 PMID:9284308

  13. Size Dependent Platelet Subpopulations: Relationship of Platelet Volume to Ultrastructure Enzymatic Activity, and Function.

    DTIC Science & Technology

    1983-03-10

    of the present apheresis instruments to separate the larger more functional platelets from the smaller ones. The selective isolation of large... PLATELET VOLUME T. -(U) BOSTON UNIV MA SCHOOL OF I MEDICINE C B THOMPSON ET RL 10 MAR 83 BUSM-93-89 UNIIDN919CA89 /68 6ilfflfllflflflflll l...N00014-79-C-0168 TECHNICAL REPORT NO. 83-08 SIZE DEPENDENT PLATELET SUBPOPULATIONS: RELATIONSHIP OF PLATELET VOLUME TO ULTRASTRUCTURE. ENZYMATIC ACTIVITY

  14. Effect of recombinant erythropoietin on functional activity of cultured human cells.

    PubMed

    Emel'yanova, E A; Kosykh, A V; Sukhanov, Yu V; Vorotelyak, E A; Vasil'ev, A V

    2012-08-01

    We studied the effect of recombinant human erythropoietin on functional activity of skin cells in vitro. It was found that erythropoietin stimulated proliferation of mesenchymal and epithelial cells and effectively protected epidermal HaCaT cells from apoptosis. Insignificant effect of erythropoietin on contraction of collagen gel by mesenchymal cells was revealed. These findings suggest that erythropoietin can be a promising component of wound-healing preparations.

  15. Tools for resolving functional activity and connectivity within intact neural circuits.

    PubMed

    Jennings, Joshua H; Stuber, Garret D

    2014-01-06

    Mammalian neural circuits are sophisticated biological systems that choreograph behavioral processes vital for survival. While the inherent complexity of discrete neural circuits has proven difficult to decipher, many parallel methodological developments promise to help delineate the function and connectivity of molecularly defined neural circuits. Here, we review recent technological advances designed to precisely monitor and manipulate neural circuit activity. We propose a holistic, multifaceted approach for unraveling how behavioral states are manifested through the cooperative interactions between discrete neurocircuit elements.

  16. Fate of Organic Functionalities Conjugated to Theranostic Nanoparticles upon Their Activation.

    PubMed

    Martinelli, Jonathan; Denkova, Antonia G; Arranja, Alexandra; Terpstra, Baukje E; Zhang, Wuyuan; Djanashvili, Kristina

    2016-02-17

    Neutron activation is widely applied for the preparation of radioactive isotopes to be used in imaging and/or therapy. The type of diagnostic/therapeutic agents varies from small chelates coordinating radioactive metal ions to complex nanoparticulate systems. Design of these agents often relies on conjugation of certain organic functionalities that determine their pharmacokinetics, biodistribution, targeting, and cell-penetrating abilities, or simply on tagging them with an optical label. The conjugation chemistry at the surface of nanoparticles and their final purification often require laborious procedures that become even more troublesome when radioactive materials are involved. This study represents a thorough investigation on the effects of neutron activation on the organic moieties of functionalized nanoparticles, with special focus on (166)Ho2O3 particles conjugated with PEG-fluorescein and PEG-polyarginine motives. Spectroscopic and thermogravimetric analyses demonstrate only a limited degradation of PEG-fluorescein upon irradiation of the particles up to 10 h using a thermal neutron flux of 5 × 10(16) m(-2) s(-1). Cell experiments show that the polyarginine-based mechanisms of membrane penetration remain unaltered after exposure of the functionalized particles to the mixed field of neutrons and gammas present during activation. This confirms that radiation damage on the PEG-polyarginines is minimal. Intrinsic radiations from (166)Ho do not seem to affect the integrity of conjugated organic material. These findings open up a new perspective to simplify the procedures for the preparation of functionalized metal-based nanosystems that need to be activated by neutron irradiation in order to be applied for diagnostic and/or therapeutic purposes.

  17. Activity-Dependent Palmitoylation Controls SynDIG1 Stability, Localization, and Function

    PubMed Central

    Kaur, Inderpreet; Yarov-Yarovoy, Vladimir; Kirk, Lyndsey M.; Plambeck, Kristopher E.; Barragan, Eden V.; Ontiveros, Eric S.

    2016-01-01

    Synapses are specialized contacts between neurons. Synapse differentiation-induced gene I (SynDIG1) plays a critical role during synapse development to regulate AMPA receptor (AMPAR) and PSD-95 content at excitatory synapses. Palmitoylation regulates the localization and function of many synaptic proteins, including AMPARs and PSD-95. Here we show that SynDIG1 is palmitoylated, and investigate the effects of palmitoylation on SynDIG1 stability and localization. Structural modeling of SynDIG1 suggests that the membrane-associated region forms a three-helical bundle with two cysteine residues located at positions 191 and 192 in the juxta-transmembrane region exposed to the cytoplasm. Site-directed mutagenesis reveals that C191 and C192 are palmitoylated in heterologous cells and positively regulates dendritic targeting in neurons. Like PSD-95, activity blockade in a rat hippocampal slice culture increases SynDIG1 palmitoylation, which is consistent with our prior demonstration that SynDIG1 localization at synapses increases upon activity blockade. These data demonstrate that palmitoylation of SynDIG1 is regulated by neuronal activity, and plays a critical role in regulating its stability and subcellular localization, and thereby its function. SIGNIFICANCE STATEMENT Palmitoylation is a reversible post-translation modification that has recently been recognized as playing a critical role in the localization and function of many synaptic proteins. Here we show that activity-dependent palmitoylation of the atypical AMPA receptor auxiliary transmembrane protein SynDIG1 regulates its stability and localization at synapses to regulate function and synaptic strength. PMID:27445135

  18. Effect of interleukin-1beta gene functional polymorphism on dorsolateral prefrontal cortex activity in schizophrenic patients.

    PubMed

    Papiol, Sergi; Molina, Vicente; Rosa, Araceli; Sanz, Javier; Palomo, Tomás; Fañanás, Lourdes

    2007-12-05

    Hypoactivity of the dorsolateral prefrontal cortex (DLPFC) during cognitive tasks is among the most consistent findings in schizophrenia. The biological factors contributing to this hypofrontality are only partially known. Previous reports have shown the influence of genes mapped to IL-1 cluster (i) in the risk to develop schizophrenia and (ii) on brain morphological abnormalities in these patients. Moreover, Interleukin-1beta (IL-1beta), encoded by IL-1B gene (IL-1 cluster, chromosome 2q13) has a key role in dopaminergic differentiation and dendrite growth in developing cortical neurons. The authors explored the role of a genetic functional polymorphism at IL-1B gene in relation to DLPFC activity. DLPFC (left and right) metabolic activity was measured in a sample of 19 DSM-IV diagnosed schizophrenic patients of Spanish origin using a procedure based on MRI/PET image fusion. During PET studies, subjects performed a contingent Continuous Performance Test aiming to activate DLPFC. Functional promoter polymorphism -511 C/T (rs16944) of IL-1B gene was genotyped in these patients. Those patients who were allele 2 (-511 T) carriers showed a lower metabolic activity in the left DLPFC with respect to patients homozygous for allele 1 (-511 C) (U = 16, z = -2.32, P = 0.02). Our results suggest that hypofrontality reported in some schizophrenic patients might be explained, at least in part, by this functional polymorphism at IL-1B gene. Genetic variants with influence on brain functionality may account for the neurocognitive heterogeneity observed in schizophrenic patients.

  19. Spatiotemporal control of microRNA function using light-activated antagomirs.

    PubMed

    Connelly, Colleen M; Uprety, Rajendra; Hemphill, James; Deiters, Alexander

    2012-11-01

    MicroRNAs (miRNAs) are small non-coding RNAs that act as post-transcriptional gene regulators and have been shown to regulate many biological processes including embryonal development, cell differentiation, apoptosis, and proliferation. Variations in the expression of certain miRNAs have been linked to a wide range of human diseases - especially cancer - and the diversity of miRNA targets suggests that they are involved in various cellular networks. Several tools have been developed to control the function of individual miRNAs and have been applied to study their biogenesis, biological role, and therapeutic potential; however, common methods lack a precise level of control that allows for the study of miRNA function with high spatial and temporal resolution. Light-activated miRNA antagomirs for mature miR-122 and miR-21 were developed through the site-specific installation of caging groups on the bases of selected nucleotides. Installation of caged nucleotides led to complete inhibition of the antagomir-miRNA hybridization and thus inactivation of antagomir function. The miRNA-inhibitory activity of the caged antagomirs was fully restored upon decaging through a brief UV irradiation. The synthesized antagomirs were applied to the photochemical regulation of miRNA function in mammalian cells. Moreover, spatial control over antagomir activity was obtained in mammalian cells through localized UV exposure. The presented approach enables the precise regulation of miRNA function and miRNA networks with unprecedented spatial and temporal resolution using UV irradiation and can be extended to any miRNA of interest.

  20. Novel aspects of blood coagulation factor XIII. I. Structure, distribution, activation, and function

    SciTech Connect

    Muszbek, L.; Adany, R.; Mikkola, H.

    1996-10-01

    Blood coagulation factor XIII (FXIII) is a protransglutaminase that becomes activated by the concerted action of thrombin and Ca{sup 2+} in the final stage of the clotting cascade. In addition to plasma, FXIII also occurs in platelets, monocytes, and monocyte-derived macrophages. While the plasma factor is a heterotetramer consisting of paired A and B subunits (A{sub 2}B{sub 2}), its cellular counterpart lacks the B subunits and is a homodimer of potentially active A subunits (A{sub 2}). The gene coding for the A and B subunits has been localized to chromosomes 6p24-25 and 1q31-32.1, respectively. The genomic as well as the primary protein structure of both subunits has been established. Plasma FXIII circulates in association with its substrate precursor, fibrinogen. Fibrin(ogen) has an important regulatory role in the activation of plasma FXIII, for instance the proteolytic removal of activation peptide by thrombin, the dissociation of subunits A and B, and the exposure of the originally buried active site on the free A subunits. The end result of this process is the formation of an active transglutaminase, which crosslinks peptide chains through {epsilon}({gamma}-glutamyl)lysyl isopeptide bonds. The protein substrates of activated FXIII include components of the clotting-fibrinolytic system, adhesive and contractile proteins. The main physiological function of plasma FXIII is to cross-link fibrin and protect it from the fibrinolytic enzyme plasmin. The latter effect is achieved mainly by covalently linking {alpha}{sub 2} antiplasmin, the most potent physiological inhibitor of plasmin, to fibrin. Plasma FXIII seems to be involved in wound healing and tissue repair, and it is essential to maintaining pregnancy. Cellular FXIII, if exposed to the surface of the cells, might support or perhaps take over the hemostatic functions of plasma FXIII; however, its intracellular role has remained mostly unexplored. 328 refs., 4 figs.

  1. Interaction between organophosphate pesticide exposure and PON1 activity on thyroid function

    SciTech Connect

    Lacasana, Marina; Lopez-Flores, Inmaculada; Rodriguez-Barranco, Miguel; Aguilar-Garduno, Clemente; Blanco-Munoz, Julia; Perez-Mendez, Oscar; Gamboa, Ricardo; Gonzalez-Alzaga, Beatriz; Bassol, Susana; Cebrian, Mariano E.

    2010-11-15

    Organophosphate pesticides are widely used in agricultural purposes. Recently, a few studies have demonstrated the ability of these chemicals to alter the function of the thyroid gland in human. Moreover, the paraoxonase-1 enzyme (PON1) plays an important role in the toxicity of some organophosphate pesticides, with low PON1 activity being associated with higher pesticide sensitivity. This study evaluates the interaction between exposure to organophosphate compounds and PON1 enzyme activity on serum levels of TSH and thyroid hormones in a population of workers occupationally exposed to pesticides. A longitudinal study was conducted on a population of floriculture workers from Mexico, during two periods of high and low-intensity levels of pesticide application. A structured questionnaire was completed by workers containing questions on sociodemographic characteristics and other variables of interest. Urine and blood samples were taken, and biomarkers of exposure (dialkylphosphates), susceptibility (PON1 polymorphisms and activity) and effect (thyroid hormone levels) were determined. Interaction between dialkylphosphates and PON1 polymorphisms or PON1 activity on hormone levels was evaluated by generalized estimating equation (GEE) models. A significant interaction was found between serum diazoxonase activity and total dialkylphosphates ({Sigma}DAP) on TSH levels. Thus, when PON1 activity was increased we observed a decrease in the percentage of variation of TSH level for each increment in one logarithmic unit of the {Sigma}DAP levels. This interaction was also observed with the PON1{sub 192}RR genotype. These results suggest a stronger association between organophosphate pesticides and thyroid function in individuals with lower PON1 activity.

  2. Active contour segmentation using level set function with enhanced image from prior intensity.

    PubMed

    Kim, Sunhee; Kim, Youngjun; Lee, Deukhee; Park, Sehyung

    2015-01-01

    This paper presents a new active contour segmentation model using a level set function that can correctly capture both the strong and the weak boundaries of a target enclosed by bright and dark regions at the same time. We introduce an enhanced image obtained from prior information about the intensity of the target. The enhanced image emphasizes the regions where pixels have intensities close to the prior intensity. This enables a desirable segmentation of an image having a partially low contrast with the target surrounded by regions that are brighter or darker than the target. We define an edge indicator function on an original image, and local and regularization forces on an enhanced image. An edge indicator function and two forces are incorporated in order to identify the strong and weak boundaries, respectively. We established an evolution equation of contours in the level set formulation and experimented with several medical images to show the performance of the proposed method.

  3. The random walk function in the analysis of time-activity curves from dynamic radionuclide studies.

    PubMed

    Hart, G C; Bunday, B; Kiri, V

    1987-04-01

    The random walk function is a mathematical function derived from studies of the mass transport and flow of diffusible materials through tubes. Approximations to the function were first used some time ago in the field of cardiac tracer dilution curves, but in the absence of rapid and reproducible curve fitting the method never became commonplace. The current study uses the latest curve-fitting techniques and shows how the method may be used with precision in the analysis of time-activity curves from dynamic oesophageal and blood flow studies. The physiological basis of the method is given and parameters obtained which relate to both the rate of flow and the local dispersion of the bolus.

  4. [Sports and recreational activities as a form of functional treatment of patients with ankylosing spondilytis].

    PubMed

    Grubisić, Frane; Grazio, Simeon; Znika, Matea

    2007-01-01

    Ankylosing spondylitis is a chronic inflammatory rheumatic disease that primarily affects the sacroiliac joints and spine, although it may involve entheses, peripheral joints and extraarticular organs. Disease treatment is directed toward the suppression of the inflammatory process and the improvement of the musculoskeletal system function. There are several treatment modalities: education of the patient and members of the family, pharmacological treatment, physical therapy and, in some cases, surgical treatment. An important segment of various modalities of physical therapy belongs to kinesitherapy, sports and recreation whose duration and intensity largely depends not only on the actual functional impairments, but also on the presence of some other disease or contraindications. Kinesitherapy is directed toward maintenance and improvement of the function of the spine, thoracic cavity and large synovial joints as well as the prevention of deformities or contractures. Kinesitherapy and sports programmes may involve individual or group approach. Patients are encouraged to participate in sports activities that may imitate or substitute specific forms of exercises.

  5. Identification of BRCA1 missense substitutions that confer partial functional activity: potential moderate risk variants?

    PubMed Central

    Lovelock, Paul K; Spurdle, Amanda B; Mok, Myth TS; Farrugia, Daniel J; Lakhani, Sunil R; Healey, Sue; Arnold, Stephen; Buchanan, Daniel; Investigators, kConFab; Couch, Fergus J; Henderson, Beric R; Goldgar, David E; Tavtigian, Sean V; Chenevix-Trench, Georgia; Brown, Melissa A

    2007-01-01

    Introduction Many of the DNA sequence variants identified in the breast cancer susceptibility gene BRCA1 remain unclassified in terms of their potential pathogenicity. Both multifactorial likelihood analysis and functional approaches have been proposed as a means to elucidate likely clinical significance of such variants, but analysis of the comparative value of these methods for classifying all sequence variants has been limited. Methods We have compared the results from multifactorial likelihood analysis with those from several functional analyses for the four BRCA1 sequence variants A1708E, G1738R, R1699Q, and A1708V. Results Our results show that multifactorial likelihood analysis, which incorporates sequence conservation, co-inheritance, segregation, and tumour immunohistochemical analysis, may improve classification of variants. For A1708E, previously shown to be functionally compromised, analysis of oestrogen receptor, cytokeratin 5/6, and cytokeratin 14 tumour expression data significantly strengthened the prediction of pathogenicity, giving a posterior probability of pathogenicity of 99%. For G1738R, shown to be functionally defective in this study, immunohistochemistry analysis confirmed previous findings of inconsistent 'BRCA1-like' phenotypes for the two tumours studied, and the posterior probability for this variant was 96%. The posterior probabilities of R1699Q and A1708V were 54% and 69%, respectively, only moderately suggestive of increased risk. Interestingly, results from functional analyses suggest that both of these variants have only partial functional activity. R1699Q was defective in foci formation in response to DNA damage and displayed intermediate transcriptional transactivation activity but showed no evidence for centrosome amplification. In contrast, A1708V displayed an intermediate transcriptional transactivation activity and a normal foci formation response in response to DNA damage but induced centrosome amplification. Conclusion

  6. Metabolic Activity and Functional Diversity Changes in Sediment Prokaryotic Communities Organically Enriched with Mussel Biodeposits

    PubMed Central

    Pollet, Thomas; Cloutier, Olivier; Nozais, Christian; McKindsey, Christopher W.; Archambault, Philippe

    2015-01-01

    This experimental microcosm study reports the influence of organic enrichments by mussel biodeposits on the metabolic activity and functional diversity of benthic prokaryotic communities. The different biodeposit enrichment regimes created, which mimicked the quantity of faeces and pseudo-faeces potentially deposited below mussel farms, show a clear stimulatory effect of this organic enrichment on prokaryotic metabolic activity. This effect was detected once a certain level of biodeposition was attained with a tipping point estimated between 3.25 and 10 g day-1 m-2. Prokaryotic communities recovered their initial metabolic activity by 11 days after the cessation of biodeposit additions. However, their functional diversity remained greater than prior to the disturbance suggesting that mussel biodeposit enrichment may disturb the functioning and perhaps the role of prokaryotic communities in benthic ecosystems. This manipulative approach provided new information on the influence of mussel biodeposition on benthic prokaryotic communities and dose-response relationships and may support the development of carrying capacity models for bivalve culture. PMID:25923715

  7. Metabolic activity and functional diversity changes in sediment prokaryotic communities organically enriched with mussel biodeposits.

    PubMed

    Pollet, Thomas; Cloutier, Olivier; Nozais, Christian; McKindsey, Christopher W; Archambault, Philippe

    2015-01-01

    This experimental microcosm study reports the influence of organic enrichments by mussel biodeposits on the metabolic activity and functional diversity of benthic prokaryotic communities. The different biodeposit enrichment regimes created, which mimicked the quantity of faeces and pseudo-faeces potentially deposited below mussel farms, show a clear stimulatory effect of this organic enrichment on prokaryotic metabolic activity. This effect was detected once a certain level of biodeposition was attained with a tipping point estimated between 3.25 and 10 g day-1 m-2. Prokaryotic communities recovered their initial metabolic activity by 11 days after the cessation of biodeposit additions. However, their functional diversity remained greater than prior to the disturbance suggesting that mussel biodeposit enrichment may disturb the functioning and perhaps the role of prokaryotic communities in benthic ecosystems. This manipulative approach provided new information on the influence of mussel biodeposition on benthic prokaryotic communities and dose-response relationships and may support the development of carrying capacity models for bivalve culture.

  8. Potential Function of Exogenous Vimentin on the Activation of Wnt Signaling Pathway in Cancer Cells

    PubMed Central

    Satelli, Arun; Hu, Jiemiao; Xia, Xueqing; Li, Shulin

    2016-01-01

    Cancer cell signaling, growth, morphology, proliferation and tumorigenic potential are largely depending on the signaling molecules present naturally in the tumor microenvironment and the identification of key molecules that drive the tumor progression is critical for the development of new modalities for the prevention of tumor progression. High concentrations of vimentin in the blood of cancer patients have been reported, however the function of blood circulating vimentin remains unknown. Here, we investigated the functional role of exogenously supplemented vimentin on colon cancer cells and examined the Wnt Signaling activation and cancer cell invasion. Vimentin when supplemented to the cancer cells remained bound to the surface of the cancer cells. Furthermore, bound vimentin activates Wnt signaling pathway as detectable by increased β-catenin accumulation in the nucleus with concomitant activation of β-catenin-dependent transcription of Wnt signaling downstream targets. Functionally, there was an increase in the rate of cellular invasion in these cancer cells upon binding with vimentin. Our results thus suggest that free vimentin in the tumor microenvironment acts as a positive regulator of the β-catenin signaling pathway, thus providing a basis for cancer invasive properties. PMID:27698922

  9. Brain activity during the flow experience: a functional near-infrared spectroscopy study.

    PubMed

    Yoshida, Kazuki; Sawamura, Daisuke; Inagaki, Yuji; Ogawa, Keita; Ikoma, Katsunori; Sakai, Shinya

    2014-06-24

    Flow is the holistic experience felt when an individual acts with total involvement. Although flow is likely associated with many functions of the prefrontal cortex (PFC), such as attention, emotion, and reward processing, no study has directly investigated the activity of the PFC during flow. The objective of this study was to examine activity in the PFC during the flow state using functional near-infrared spectroscopy (fNIRS). Twenty right-handed university students performed a video game task under conditions designed to induce psychological states of flow and boredom. During each task and when completing the flow state scale for occupational tasks, change in oxygenated hemoglobin (oxy-Hb) concentration in frontal brain regions was measured using fNIRS. During the flow condition, oxy-Hb concentration was significantly increased in the right and left ventrolateral prefrontal cortex. Oxy-Hb concentration tended to decrease in the boredom condition. There was a significant increase in oxy-Hb concentration in the right and left dorsolateral prefrontal cortex, right and left frontal pole areas, and left ventrolateral PFC when participants were completing the flow state scale after performing the task in the flow condition. In conclusion, flow is associated with activity of the PFC, and may therefore be associated with functions such as cognition, emotion, maintenance of internal goals, and reward processing.

  10. Cavitand-functionalized porous silicon as an active surface for organophosphorus vapor detection.

    PubMed

    Tudisco, Cristina; Betti, Paolo; Motta, Alessandro; Pinalli, Roberta; Bombaci, Luigi; Dalcanale, Enrico; Condorelli, Guglielmo G

    2012-01-24

    This paper reports on the preparation of a porous silicon-based material covalently functionalized with cavitand receptors suited for the detection of organophosphorus vapors. Two different isomeric cavitands, both containing one acid group at the upper rim, specifically designed for covalent anchoring on silicon, were grafted on H-terminated porous silicon (PSi) by thermal hydrosilylation. The covalently functionalized surfaces and their complexation properties were characterized by combining different analytical techniques, namely X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and mass spectroscopy analysis coupled with thermal desorption experiments. Complexation experiments were performed by exposing both active surfaces and a control surface consisting of PSi functionalized with a structurally similar but inactive methylene-bridged cavitand (MeCav) to dimethyl methylphosphonate (DMMP) vapors. Comparison between active and inactive surfaces demonstrated the recognition properties of the new surfaces. Finally, the nature of the involved interactions, the energetic differences between active and inactive surfaces toward DMMP complexation, and the comparison with a true nerve gas agent (sarin) were studied by DFT modeling. The results revealed the successful grafting reaction, the specific host-guest interactions of the PSi-bonded receptors, and the reversibility of the guest complexation.

  11. Activated NKT cells imprint NK-cell differentiation, functionality and education.

    PubMed

    Riese, Peggy; Trittel, Stephanie; May, Tobias; Cicin-Sain, Luka; Chambers, Benedict J; Guzmán, Carlos A

    2015-06-01

    NK cells represent a vital component of the innate immune system. The recent discoveries demonstrating that the functionality of NK cells depends on their differentiation and education status underscore their potential as targets for immune intervention. However, to exploit their full potential, a detailed understanding of the cellular interactions involved in these processes is required. In this regard, the cross-talk between NKT cells and NK cells needs to be better understood. Our results provide strong evidence for NKT cell-induced effects on key biological features of NK cells. NKT-cell activation results in the generation of highly active CD27(high) NK cells with improved functionality. In this context, degranulation activity and IFNγ production were mainly detected in the educated subset. In a mCMV infection model, we also demonstrated that NKT-cell stimulation induced the generation of highly functional educated and uneducated NK cells, crucial players in viral control. Thus, our findings reveal new fundamental aspects of the NKT-NK cell axis that provide important hints for the manipulation of NK cells in clinical settings.

  12. Amine-functionalized, silver-exchanged zeolite NaY: Preparation, characterization and antibacterial activity

    NASA Astrophysics Data System (ADS)

    Hanim, Siti Aishah Mohd; Malek, Nik Ahmad Nizam Nik; Ibrahim, Zaharah

    2016-01-01

    Amine-functionalized, silver-exchanged zeolite NaY (ZSA) were prepared with three different concentrations of 3-aminopropyltriethoxysilane (APTES) (0.01, 0.20 and 0.40 M) and four different concentrations of silver ions (25%, 50%, 100% and 200% from zeolite cation exchange capacity (CEC)). The samples were characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray (EDX), surface area analysis, thermogravimetric analysis (TGA) and zeta potential (ZP) analysis. The FTIR results indicated that the zeolite was functionalized by APTES and that the intensity of the peaks corresponding to APTES increased as the concentration of APTES used was increased. The antibacterial activities of the silver-exchanged zeolite NaY (ZS) and ZSA were studied against Escherichia coli ATCC11229 and Staphylococcus aureus ATCC6538 using the disc diffusion technique (DDT) and minimum inhibitory concentration (MIC). The antibacterial activity of ZSA increased with the increase in APTES on ZS, and E. coli was more susceptible towards the sample compared to S. aureus. The FESEM micrographs of the bacteria after contact with the ZSA suggested different mechanisms of bacterial death for these two bacteria due to exposure to the studied sample. The functionalization of ZS with APTES improved the antibacterial activity of the silver-zeolite, depending on the concentration of silver ions and APTES used during modification.

  13. Heterogeneous nucleotide occupancy stimulates functionality of phage shock protein F, an AAA+ transcriptional activator.

    PubMed

    Joly, Nicolas; Schumacher, Jörg; Buck, Martin

    2006-11-17

    The catalytic AAA+ domain (PspF1-275) of an enhancer-binding protein is necessary and sufficient to contact sigma54-RNA polymerase holoenzyme (Esigma54), remodel it, and in so doing catalyze open promoter complex formation. Whether ATP binding and hydrolysis is coordinated between subunits of PspF and the precise nature of the nucleotide(s) bound to the oligomeric forms responsible for substrate remodeling are unknown. We demonstrate that ADP stimulates the intrinsic ATPase activity of PspF1-275 and propose that this heterogeneous nucleotide occupancy in a PspF1-275 hexamer is functionally important for specific activity. Binding of ADP and ATP triggers the formation of functional PspF1-275 hexamers as shown by a gain of specific activity. Furthermore, ATP concentrations congruent with stoichiometric ATP binding to PspF1-275 inhibit ATP hydrolysis and Esigma54-promoter open complex formation. Demonstration of a heterogeneous nucleotide-bound state of a functional PspF1-275.Esigma54 complex provides clear biochemical evidence for heterogeneous nucleotide occupancy in this AAA+ protein. Based on our data, we propose a stochastic nucleotide binding and a coordinated hydrolysis mechanism in PspF1-275 hexamers.

  14. Novel Active Surface Prepared by Embedded Functionalized Clays in an Acrylate Coating.

    PubMed

    Xia, Yining; Ghasemlou, Mehran; Rubino, Maria; Auras, Rafael; Baghdachi, Jamil

    2015-11-11

    The research on a self-decontaminating surface has received significant attention because of the growth of pathogenic microorganisms on surfaces. In this study, a novel and simple technique for producing an active surface with antimicrobial functionality is demonstrated. A tethering platform was developed by grafting the biocide ampicillin (Amp) to a nanoclay and dispersing the nanoclay in a UV-curable acrylate coating applied on polypropylene films as the substrate. A coupling agent, [3-(glycidyloxy)propyl]trimethoxysilane, was used as a linker between the nanoclay and Amp. The Amp-functionalized clay was further modified with an organic surfactant to improve the compatibility with the coating. Several characterization assays, such as Fourier infrared transform analysis, thermogravimetric analysis, and X-ray diffraction, were conducted to confirm the presence of Amp in the nanoclay. Transmission electron microscopy images revealed that the clay particles were well dispersed in the coating and had a partial exfoliated morphology. The active coating surface was effective in inhibiting the growth of Gram-positive Listeria monocytogenes and Gram-negative Salmonella Typhimurium via contact. These findings suggest the potential for the development of active surfaces with the implementation of nanotechnology to achieve diverse functionalities.

  15. Melittin modulates keratinocyte function through P2 receptor-dependent ADAM activation.

    PubMed

    Sommer, Anselm; Fries, Anja; Cornelsen, Isabell; Speck, Nancy; Koch-Nolte, Friedrich; Gimpl, Gerald; Andrä, Jörg; Bhakdi, Sucharit; Reiss, Karina

    2012-07-06

    Melittin, the major component of the bee venom, is an amphipathic, cationic peptide with a wide spectrum of biological properties that is being considered as an anti-inflammatory and anti-cancer agent. It modulates multiple cellular functions but the underlying mechanisms are not clearly understood. Here, we report that melittin activates disintegrin-like metalloproteases (ADAMs) and that downstream events likely contribute to the biological effects evoked by the peptide. Melittin stimulated the proteolysis of ADAM10 and ADAM17 substrates in human neutrophil granulocytes, endothelial cells and murine fibroblasts. In human HaCaT keratinocytes, melittin induced shedding of the adhesion molecule E-cadherin and release of TGF-α, which was accompanied by transactivation of the EGF receptor and ERK1/2 phosphorylation. This was followed by functional consequences such as increased keratinocyte proliferation and enhanced cell migration. Evidence is provided that ATP release and activation of purinergic P2 receptors are involved in melittin-induced ADAM activation. E-cadherin shedding and EGFR phosphorylation were dose-dependently reduced in the presence of ATPases or P2 receptor antagonists. The involvement of P2 receptors was underscored in experiments with HEK cells, which lack the P2X7 receptor and showed strikingly increased response to melittin stimulation after transfection with this receptor. Our study provides new insight into the mechanism of melittin function which should be of interest particularly in the context of its potential use as an anti-inflammatory or anti-cancer agent.

  16. Acetylation of pregnane X receptor protein determines selective function independent of ligand activation

    SciTech Connect

    Biswas, Arunima; Pasquel, Danielle; Tyagi, Rakesh Kumar; Mani, Sridhar

    2011-03-18

    Research highlights: {yields} Pregnane X receptor (PXR), a major regulatory protein, is modified by acetylation. {yields} PXR undergoes dynamic deacetylation upon ligand-mediated activation. {yields} SIRT1 partially mediates PXR deacetylation. {yields} PXR deacetylation per se induces lipogenesis mimicking ligand-mediated activation. -- Abstract: Pregnane X receptor (PXR), like other members of its class of nuclear receptors, undergoes post-translational modification [PTM] (e.g., phosphorylation). However, it is unknown if acetylation (a major and common form of protein PTM) is observed on PXR and, if it is, whether it is of functional consequence. PXR has recently emerged as an important regulatory protein with multiple ligand-dependent functions. In the present work we show that PXR is indeed acetylated in vivo. SIRT1 (Sirtuin 1), a NAD-dependent class III histone deacetylase and a member of the sirtuin family of proteins, partially mediates deacetylation of PXR. Most importantly, the acetylation status of PXR regulates its selective function independent of ligand activation.

  17. Effect of heroin-conditioned auditory stimuli on cerebral functional activity in rats

    SciTech Connect

    Trusk, T.C.; Stein, E.A.

    1988-08-01

    Cerebral functional activity was measured as changes in distribution of the free fatty acid (1-14C)octanoate in autoradiograms obtained from rats during brief presentation of a tone previously paired to infusions of heroin or saline. Rats were trained in groups of three consisting of one heroin self-administering animal and two animals receiving yoked infusions of heroin or saline. Behavioral experiments in separate groups of rats demonstrated that these training parameters imparts secondary reinforcing properties to the tone for animals self-administering heroin while the tone remains behaviorally neutral in yoked-infusion animals. The optical densities of thirty-seven brain regions were normalized to a relative index for comparisons between groups. Previous pairing of the tone to heroin infusions irrespective of behavior (yoked-heroin vs. yoked-saline groups) produced functional activity changes in fifteen brain areas. In addition, nineteen regional differences in octanoate labeling density were evident when comparison was made between animals previously trained to self-administer heroin to those receiving yoked-heroin infusions, while twelve differences were noted when comparisons were made between the yoked vehicle and self administration group. These functional activity changes are presumed related to the secondary reinforcing capacity of the tone acquired by association with heroin, and may identify neural substrates involved in auditory signalled conditioning of positive reinforcement to opiates.

  18. Brain activation to negative stimuli mediates a relationship between adolescent marijuana use and later emotional functioning

    PubMed Central

    Heitzeg, Mary M.; Cope, Lora M.; Martz, Meghan E.; Hardee, Jillian E.; Zucker, Robert A.

    2015-01-01

    This work investigated the impact of heavy marijuana use during adolescence on emotional functioning, as well as the brain functional mediators of this effect. Participants (n=40) were recruited from the Michigan Longitudinal Study (MLS). Data on marijuana use were collected prospectively beginning in childhood as part of the MLS. Participants were classified as heavy marijuana users (n=20) or controls with minimal marijuana use. Two facets of emotional functioning—negative emotionality and resiliency (a self-regulatory mechanism)—were assessed as part of the MLS at three time points: mean age 13.4; mean age 19.6; and mean age 23.1. Functional neuroimaging data during an emotion-arousal word task were collected at mean age 20.2.Negative emotionality decreased and resiliency increased across the three time points in controls but not heavy marijuana users. Compared with controls, heavy marijuana users had less activation to negative words in temporal, prefrontal, and occipital cortices, insula, and amygdala. Activation of dorsolateral prefrontal cortex to negative words mediated an association between marijuana group and later negative emotionality. Activation of the cuneus/lingual gyrus mediated an association between marijuana group and later resiliency. Results support growing evidence that heavy marijuana use during adolescence affects later emotional outcomes. PMID:26403581

  19. Fetal Functional Brain Age Assessed from Universal Developmental Indices Obtained from Neuro-Vegetative Activity Patterns

    PubMed Central

    Hoyer, Dirk; Tetschke, Florian; Jaekel, Susan; Nowack, Samuel; Witte, Otto W.; Schleußner, Ekkehard; Schneider, Uwe

    2013-01-01

    Fetal brain development involves the development of the neuro-vegetative (autonomic) control that is mediated by the autonomic nervous system (ANS). Disturbances of the fetal brain development have implications for diseases in later postnatal life. In that context, the fetal functional brain age can be altered. Universal principles of developmental biology applied to patterns of autonomic control may allow a functional age assessment. The work aims at the development of a fetal autonomic brain age score (fABAS) based on heart rate patterns. We analysed n = 113 recordings in quiet sleep, n = 286 in active sleep, and n = 29 in active awakeness from normals. We estimated fABAS from magnetocardiographic recordings (21.4–40.3 weeks of gestation) preclassified in quiet sleep (n = 113, 63 females) and active sleep (n = 286, 145 females) state by cross-validated multivariate linear regression models in a cross-sectional study. According to universal system developmental principles, we included indices that address increasing fluctuation range, increasing complexity, and pattern formation (skewness, power spectral ratio VLF/LF, pNN5). The resulting models constituted fABAS. fABAS explained 66/63% (coefficient of determination R2 of training and validation set) of the variance by age in quiet, while 51/50% in active sleep. By means of a logistic regression model using fluctuation range and fetal age, quiet and active sleep were automatically reclassified (94.3/93.1% correct classifications). We did not find relevant gender differences. We conclude that functional brain age can be assessed based on universal developmental indices obtained from autonomic control patterns. fABAS reflect normal complex functional brain maturation. The presented normative data are supplemented by an explorative study of 19 fetuses compromised by intrauterine growth restriction. We observed a shift in the state distribution towards active awakeness. The lower WGA dependent f

  20. Muscle Strength, Physical Activity, and Functional Limitations in Older Adults with Central Obesity

    PubMed Central

    Germain, Cassandra M.; Batsis, John A.; Vasquez, Elizabeth; McQuoid, Douglas R.

    2016-01-01

    Background. Obesity and muscle weakness are independently associated with increased risk of physical and functional impairment in older adults. It is unknown whether physical activity (PA) and muscle strength combined provide added protection against functional impairment. This study examines the association between muscle strength, PA, and functional outcomes in older adults with central obesity. Methods. Prevalence and odds of physical (PL), ADL, and IADL limitation were calculated for 6,388 community dwelling adults aged ≥ 60 with central obesity. Individuals were stratified by sex-specific hand grip tertiles and PA. Logistic models were adjusted for age, education, comorbidities, and body-mass index and weighted. Results. Overall prevalence of PL and ADL and IADL limitations were progressively lower by grip category. Within grip categories, prevalence was lower for individuals who were active than those who were inactive. Adjusted models showed significantly lower odds of PL OR 0.42 [0.31, 0.56]; ADL OR 0.60 [0.43, 0.84], and IADL OR 0.46 [0.35, 0.61] for those in the highest grip strength category as compared to those in the lowest grip category. Conclusion. Improving grip strength in obese elders who are not able to engage in traditional exercise is important for reducing odds of physical and functional impairment. PMID:27034833

  1. Polyphenol-Rich Propolis Extracts Strengthen Intestinal Barrier Function by Activating AMPK and ERK Signaling.

    PubMed

    Wang, Kai; Jin, Xiaolu; Chen, Yifan; Song, Zehe; Jiang, Xiasen; Hu, Fuliang; Conlon, Michael A; Topping, David L

    2016-05-07

    Propolis has abundant polyphenolic constituents and is used widely as a health/functional food. Here, we investigated the effects of polyphenol-rich propolis extracts (PPE) on intestinal barrier function in human intestinal epithelial Caco-2 cells, as well as in rats. In Caco-2 cells, PPE increased transepithelial electrical resistance and decreased lucifer yellow flux. PPE-treated cells showed increased expression of the tight junction (TJ) loci occludin and zona occludens (ZO)-1. Confocal microscopy showed organized expressions in proteins related to TJ assembly, i.e., occludin and ZO-1, in response to PPE. Furthermore, PPE led to the activation of AMPK, ERK1/2, p38, and Akt. Using selective inhibitors, we found that the positive effects of PPE on barrier function were abolished in cells in which AMPK and ERK1/2 signaling were inhibited. Moreover, rats fed a diet supplemented with PPE (0.3% in the diet) exhibited increased colonic epithelium ZO-1 expression. Overall, these data suggest that PPE strengthens intestinal barrier function by activating AMPK and ERK signaling and provide novel insights into the potential application of propolis for human gut health.

  2. Reverse evolution leads to genotypic incompatibility despite functional and active site convergence

    PubMed Central

    Kaltenbach, Miriam; Jackson, Colin J; Campbell, Eleanor C; Hollfelder, Florian; Tokuriki, Nobuhiko

    2015-01-01

    Understanding the extent to which enzyme evolution is reversible can shed light on the fundamental relationship between protein sequence, structure, and function. Here, we perform an experimental test of evolutionary reversibility using directed evolution from a phosphotriesterase to an arylesterase, and back, and examine the underlying molecular basis. We find that wild-type phosphotriesterase function could be restored (>104-fold activity increase), but via an alternative set of mutations. The enzyme active site converged towards its original state, indicating evolutionary constraints imposed by catalytic requirements. We reveal that extensive epistasis prevents reversions and necessitates fixation of new mutations, leading to a functionally identical sequence. Many amino acid exchanges between the new and original enzyme are not tolerated, implying sequence incompatibility. Therefore, the evolution was phenotypically reversible but genotypically irreversible. Our study illustrates that the enzyme's adaptive landscape is highly rugged, and different functional sequences may constitute separate fitness peaks. DOI: http://dx.doi.org/10.7554/eLife.06492.001 PMID:26274563

  3. Polyphenol-Rich Propolis Extracts Strengthen Intestinal Barrier Function by Activating AMPK and ERK Signaling

    PubMed Central

    Wang, Kai; Jin, Xiaolu; Chen, Yifan; Song, Zehe; Jiang, Xiasen; Hu, Fuliang; Conlon, Michael A.; Topping, David L.

    2016-01-01

    Propolis has abundant polyphenolic constituents and is used widely as a health/functional food. Here, we investigated the effects of polyphenol-rich propolis extracts (PPE) on intestinal barrier function in human intestinal epithelial Caco-2 cells, as well as in rats. In Caco-2 cells, PPE increased transepithelial electrical resistance and decreased lucifer yellow flux. PPE-treated cells showed increased expression of the tight junction (TJ) loci occludin and zona occludens (ZO)-1. Confocal microscopy showed organized expressions in proteins related to TJ assembly, i.e., occludin and ZO-1, in response to PPE. Furthermore, PPE led to the activation of AMPK, ERK1/2, p38, and Akt. Using selective inhibitors, we found that the positive effects of PPE on barrier function were abolished in cells in which AMPK and ERK1/2 signaling were inhibited. Moreover, rats fed a diet supplemented with PPE (0.3% in the diet) exhibited increased colonic epithelium ZO-1 expression. Overall, these data suggest that PPE strengthens intestinal barrier function by activating AMPK and ERK signaling and provide novel insights into the potential application of propolis for human gut health. PMID:27164138

  4. Relationship between physical activity and function in elderly patients discharged after surgical treatment for gastrointestinal cancer

    PubMed Central

    Hara, Tsuyoshi; Kubo, Akira

    2015-01-01

    [Purpose] The purpose of the present study was to observe changes in physical activity (PA) from before surgery to after discharge among elderly patients with gastrointestinal cancer and to examine the relationships between PA, function, and physique after discharge in these patients. [Subjects and Methods] The study participants were 18 elderly patients who underwent surgical treatment for gastrointestinal cancer [10 males and 8 females, aged 71.4 ± 4.2 years (mean ± SD)]. We evaluated patients’ PA, function, and physique before surgery and after discharge. Calorie consumption as calculated using the International Physical Activity Questionnaire (IPAQ) short version was measured for PA. Isometric knee extension force (IKEF), the timed up and go test (TUGT), and the 6-minute walk distance (6MWD) were measured for function. The body mass index (BMI) was calculated for physique. [Results] Significant declines in PA and BMI were observed after discharge among the study participants. In addition, a significant correlation between PA and IKEF was observed in the discharge phase. [Conclusion] These results suggest that PA after discharge is significantly less than that before surgery and related to the functioning of the lower extremities in the same period in elderly patients who undergo surgical treatment for gastrointestinal cancer. PMID:26504327

  5. Ankyrin domain of myosin 16 influences motor function and decreases protein phosphatase catalytic activity.

    PubMed

    Kengyel, András; Bécsi, Bálint; Kónya, Zoltán; Sellers, James R; Erdődi, Ferenc; Nyitrai, Miklós

    2015-05-01

    The unconventional myosin 16 (Myo16), which may have a role in regulation of cell cycle and cell proliferation, can be found in both the nucleus and the cytoplasm. It has a unique, eight ankyrin repeat containing pre-motor domain, the so-called ankyrin domain (My16Ank). Ankyrin repeats are present in several other proteins, e.g., in the regulatory subunit (MYPT1) of the myosin phosphatase holoenzyme, which binds to the protein phosphatase-1 catalytic subunit (PP1c). My16Ank shows sequence similarity to MYPT1. In this work, the interactions of recombinant and isolated My16Ank were examined in vitro. To test the effects of My16Ank on myosin motor function, we used skeletal muscle myosin or nonmuscle myosin 2B. The results showed that My16Ank bound to skeletal muscle myosin (K D ≈ 2.4 µM) and the actin-activated ATPase activity of heavy meromyosin (HMM) was increased in the presence of My16Ank, suggesting that the ankyrin domain can modulate myosin motor activity. My16Ank showed no direct interaction with either globular or filamentous actin. We found, using a surface plasmon resonance-based binding technique, that My16Ank bound to PP1cα (K D ≈ 540 nM) and also to PP1cδ (K D ≈ 600 nM) and decreased its phosphatase activity towards the phosphorylated myosin regulatory light chain. Our results suggest that one function of the ankyrin domain is probably to regulate the function of Myo16. It may influence the motor activity, and in complex with the PP1c isoforms, it can play an important role in the targeted dephosphorylation of certain, as yet unidentified, intracellular proteins.

  6. Expanded Hematopoietic Progenitor Cells Reselected for High Aldehyde Dehydrogenase Activity Demonstrate Islet Regenerative Functions.

    PubMed

    Seneviratne, Ayesh K; Bell, Gillian I; Sherman, Stephen E; Cooper, Tyler T; Putman, David M; Hess, David A

    2016-04-01

    Human umbilical cord blood (UCB) hematopoietic progenitor cells (HPC) purified for high aldehyde dehydrogenase activity (ALDH(hi) ) stimulate islet regeneration after transplantation into mice with streptozotocin-induced β cell deletion. However, ALDH(hi) cells represent a rare progenitor subset and widespread use of UCB ALDH(hi) cells to stimulate islet regeneration will require progenitor cell expansion without loss of islet regenerative functions. Here we demonstrate that prospectively purified UCB ALDH(hi) cells expand efficiently under serum-free, xeno-free conditions with minimal growth factor supplementation. Consistent with the concept that ALDH-activity is decreased as progenitor cells differentiate, kinetic analyses over 9 days revealed the frequency of ALDH(hi) cells diminished as culture time progressed such that total ALDH(hi) cell number was maximal (increased 3-fold) at day 6. Subsequently, day 6 expanded cells (bulk cells) were sorted after culture to reselect differentiated progeny with low ALDH-activity (ALDH(lo) subset) from less differentiated progeny with high ALDH-activity (ALDH(hi) subset). The ALDH(hi) subset retained primitive cell surface marker coexpression (32.0% ± 7.0% CD34(+) /CD38(-) cells, 37.0% ± 6.9% CD34(+) /CD133(+) cells), and demonstrated increased hematopoietic colony forming cell function compared with the ALDH(lo) subset. Notably, bulk cells or ALDH(lo) cells did not possess the functional capacity to lower hyperglycemia after transplantation into streptozotocin-treated NOD/SCID mice. However, transplantation of the repurified ALDH(hi) subset significantly reduced hyperglycemia, improved glucose tolerance, and increased islet-associated cell proliferation and capillary formation. Thus, expansion and delivery of reselected UCB cells that retain high ALDH-activity after short-term culture represents an improved strategy for the development of cellular therapies to enhance islet regeneration in situ.

  7. Enhanced calcium cycling and contractile function in transgenic hearts expressing constitutively active G alpha o* protein.

    PubMed

    Zhu, Ming; Gach, Agnieszka A; Liu, GongXin; Xu, Xiaomei; Lim, Chee Chew; Zhang, Julie X; Mao, Lan; Chuprun, Kurt; Koch, Walter J; Liao, Ronglih; Koren, Gideon; Blaxall, Burns C; Mende, Ulrike

    2008-03-01

    In contrast to the other heterotrimeric GTP-binding proteins (G proteins) Gs and Gi, the functional role of G o is still poorly defined. To investigate the role of G alpha o in the heart, we generated transgenic mice with cardiac-specific expression of a constitutively active form of G alpha o1* (G alpha o*), the predominant G alpha o isoform in the heart. G alpha o expression was increased 3- to 15-fold in mice from 5 independent lines, all of which had a normal life span and no gross cardiac morphological abnormalities. We demonstrate enhanced contractile function in G alpha o* transgenic mice in vivo, along with increased L-type Ca2+ channel current density, calcium transients, and cell shortening in ventricular G alpha o*-expressing myocytes compared with wild-type controls. These changes were evident at baseline and maintained after isoproterenol stimulation. Expression levels of all major Ca2+ handling proteins were largely unchanged, except for a modest reduction in Na+/Ca2+ exchanger in transgenic ventricles. In contrast, phosphorylation of the ryanodine receptor and phospholamban at known PKA sites was increased 1.6- and 1.9-fold, respectively, in G alpha o* ventricles. Density and affinity of beta-adrenoceptors, cAMP levels, and PKA activity were comparable in G alpha o* and wild-type myocytes, but protein phosphatase 1 activity was reduced upon G alpha o* expression, particularly in the vicinity of the ryanodine receptor. We conclude that G alpha o* exerts a positive effect on Ca2+ cycling and contractile function. Alterations in protein phosphatase 1 activity rather than PKA-mediated phosphorylation might be involved in hyperphosphorylation of key Ca2+ handling proteins in hearts with constitutive G alpha o activation<