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Sample records for activation functions af-1

  1. Potentiation of estrogen receptor activation function 1 (AF-1) by Src/JNK through a serine 118-independent pathway.

    PubMed

    Feng, W; Webb, P; Nguyen, P; Liu, X; Li, J; Karin, M; Kushner, P J

    2001-01-01

    Estrogen receptor (ER) is activated either by ligand or by signals from tyrosine kinase-linked cell surface receptors. We investigated whether the nonreceptor Src tyrosine kinase could affect ER activity. Expression of constitutively active Src or stimulation of the endogenous Src/JNK pathway enhances transcriptional activation by the estrogen-ER complex and strongly stimulates the otherwise weak activation by the unliganded ER and the tamoxifen-ER complex. Src affects ER activation function 1 (AF-1), and not ER AF-2, and does so through its tyrosine kinase activity. This effect of Src is mediated partly through a Raf/mitogen-activated ERK kinase/extracellular signal-regulated kinase (Raf/MEK/ERK) signaling cascade and partly through a MEKK/JNKK/JNK cascade. Although, as previously shown, Src action through activated ERK stimulates AF-1 by phosphorylation at S118, Src action through activated JNK neither leads to phosphorylation of S118 nor requires S118 for its action. We therefore suggest that the Src/JNK pathway enhances AF-1 activity by modification of ER AF-1-associated proteins. Src potentiates activation functions in CREB-binding protein (CBP) and glucocorticoid receptor interacting protein 1 (GRIP1), and we discuss the possibility that the Src/JNK pathway enhances the activity of these coactivators, which are known to mediate AF-1 action. PMID:11145737

  2. AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis

    PubMed Central

    Park, Jino; Schlederer, Michaela; Schreiber, Martin; Ice, Ryan; Merkel, Olaf; Bilban, Martin; Hofbauer, Sebastian; Kim, Soojin; Addison, Joseph; Zou, Jie; Ji, Chunyan; Bunting, Silvia T.; Wang, Zhengqi; Shoham, Menachem; Huang, Gang; Bago-Horvath, Zsuzsanna; Gibson, Laura F.; Rojanasakul, Yon; Remick, Scot; Ivanov, Alexey; Pugacheva, Elena; Bunting, Kevin D.; Moriggl, Richard

    2015-01-01

    AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent “metastatic founder cells” which have invasive properties. PMID:26079538

  3. Identification and functional characterization of grass carp IL-17A/F1: An evaluation of the immunoregulatory role of teleost IL-17A/F1.

    PubMed

    Du, Linyong; Feng, Shiyu; Yin, Licheng; Wang, Xinyan; Zhang, Anying; Yang, Kun; Zhou, Hong

    2015-07-01

    In mammals, IL-17A and IL-17F are hallmark cytokines of Th17 cells which act significant roles in eradicating extracellular pathogens. IL-17A and IL-17F homologs nominated as IL-17A/F1-3 have been revealed in fish and their functions remain largely undefined. Here we identified and characterized grass carp IL-17A/F1 (gcIL-17A/F1) in fish immune system. In this regard, both tissue distribution and inductive expression of gcIL-17A/F1 indicated its possible involvement in immune response. Moreover, recombinant gcIL-17A/F1 (rgcIL-17A/F1) was prepared and displayed an ability to enhance pro-inflammatory cytokines (IL-1β, TNF-α and IL-6) mRNA expression in head kidney leukocytes. It is suggestive of that gcIL-17A/F1 may act as a proinflammatory cytokine in fish immunity. Besides, rgcIL-17A/F1 induced gene expression and protein release of grass carp chemokine CXCL-8 (gcCXCL-8) in head kidney cells (HKCs), probably via NF-κB, p38 and Erk1/2 pathways. In particular, culture medium from the HKCs treated by rgcIL-17A/F1 could stimulate peripheral blood leukocytes migration and immunoneutralization of endogenous gcCXCL-8 could partially attenuate this stimulation, suggesting that rgcIL-17A/F1 could recruit immune cells through producing gcCXCL-8 as mammalian IL-17 A and F. Taken together, we not only identified the pro-inflammatory role of gcIL-17A/F1 in host defense, but also provided the basis for clarifying Th17 cells in teleost. PMID:25847875

  4. POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes.

    PubMed

    Zhou, Haixia; Brekman, Angelika; Zuo, Wu-Lin; Ou, Xuemei; Shaykhiev, Renat; Agosto-Perez, Francisco J; Wang, Rui; Walters, Matthew S; Salit, Jacqueline; Strulovici-Barel, Yael; Staudt, Michelle R; Kaner, Robert J; Mezey, Jason G; Crystal, Ronald G; Wang, Guoqing

    2016-04-01

    In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU domain class 2-associating factor 1 (POU2AF1), a known transcription cofactor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of upregulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation, and analysis of differentiating single basal cell clones. Lentivirus-mediated upregulation of POU2AF1 in airway basal cells induced upregulation of host defense genes, including MX1, IFIT3, IFITM, and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, and BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a host defense tone even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium. PMID:26927796

  5. POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes.

    PubMed

    Zhou, Haixia; Brekman, Angelika; Zuo, Wu-Lin; Ou, Xuemei; Shaykhiev, Renat; Agosto-Perez, Francisco J; Wang, Rui; Walters, Matthew S; Salit, Jacqueline; Strulovici-Barel, Yael; Staudt, Michelle R; Kaner, Robert J; Mezey, Jason G; Crystal, Ronald G; Wang, Guoqing

    2016-04-01

    In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU domain class 2-associating factor 1 (POU2AF1), a known transcription cofactor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of upregulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation, and analysis of differentiating single basal cell clones. Lentivirus-mediated upregulation of POU2AF1 in airway basal cells induced upregulation of host defense genes, including MX1, IFIT3, IFITM, and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, and BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a host defense tone even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium.

  6. Functional dissection of an enhancer-like element located within the second intron of the human U2AF1L4 gene.

    PubMed

    Didych, D A; Smirnov, N A; Kotova, E S; Akopov, S B; Nikolaev, L G; Sverdlov, E D

    2011-08-01

    A detailed functional and evolutionary analysis of an enhancer element of the human genome (enhancer 12) located in the second intron of the U2AF1L4 gene, which we identified earlier, is presented. Overlapping fragments of the studied genome region were analyzed for enhancer activity, and the site responsible for the activity of this element was identified using transient transfections of HeLa cells. Comparison of the enhancer 12 sequence with orthologous sequences from seven primate species revealed the existence of evolutionarily conserved sequences within this element. One of the identified conservative regions is likely responsible for the enhancer activity and is able to specifically interact in vitro with proteins of HeLa cell nuclear extract. The ability of orthologous primate sequences to compete with enhancer 12 for binding with HeLa cell nuclear extract proteins and to enhance the activity of the reporter gene in transient transfection of HeLa cells is demonstrated. PMID:22022969

  7. Degradation of AF1Q by chaperone-mediated autophagy

    SciTech Connect

    Li, Peng; Ji, Min; Lu, Fei; Zhang, Jingru; Li, Huanjie; Cui, Taixing; Li Wang, Xing; Tang, Dongqi; Ji, Chunyan

    2014-09-10

    AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated autophagy (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas activators of CMA, including 6-aminonicotinamide and nutrient starvation, decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. Using an amino acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion, we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA. - Highlights: • Chaperone-mediated autophagy (CMA) is involved in the degradation of AF1Q. • Macroautophagy does not contribute to the AF1Q degradation. • AF1Q has a KFERQ-like motif that is recognized by CMA core components.

  8. Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction

    PubMed Central

    Washington, Erica J.; Mukhtar, M. Shahid; Finkel, Omri M.; Wan, Li; Kieber, Joseph J.; Dangl, Jeffery L.

    2016-01-01

    HopAF1 is a type III effector protein of unknown function encoded in the genomes of several strains of Pseudomonas syringae and other plant pathogens. Structural modeling predicted that HopAF1 is closely related to deamidase proteins. Deamidation is the irreversible substitution of an amide group with a carboxylate group. Several bacterial virulence factors are deamidases that manipulate the activity of specific host protein substrates. We identified Arabidopsis methylthioadenosine nucleosidase proteins MTN1 and MTN2 as putative targets of HopAF1 deamidation. MTNs are enzymes in the Yang cycle, which is essential for the high levels of ethylene biosynthesis in Arabidopsis. We hypothesized that HopAF1 inhibits the host defense response by manipulating MTN activity and consequently ethylene levels. We determined that bacterially delivered HopAF1 inhibits ethylene biosynthesis induced by pathogen-associated molecular patterns and that Arabidopsis mtn1 mtn2 mutant plants phenocopy the effect of HopAF1. Furthermore, we identified two conserved asparagines in MTN1 and MTN2 from Arabidopsis that confer loss of function phenotypes when deamidated via site-specific mutation. These residues are potential targets of HopAF1 deamidation. HopAF1-mediated manipulation of Yang cycle MTN proteins is likely an evolutionarily conserved mechanism whereby HopAF1 orthologs from multiple plant pathogens contribute to disease in a large variety of plant hosts. PMID:27274076

  9. Patterns of missplicing due to somatic U2AF1 mutations in myeloid neoplasms

    PubMed Central

    Przychodzen, Bartlomiej; Jerez, Andres; Guinta, Kathryn; Sekeres, Mikkael A.; Padgett, Richard; Maciejewski, Jaroslaw P.

    2013-01-01

    Recently, recurrent mutations of spliceosomal genes were frequently identified in myeloid malignancies, as well as other types of cancers. One of these spliceosomal genes, U2AF1, was affected by canonical somatic mutations in aggressive type of myeloid malignancies. We hypothesized that U2AF1 mutations causes defects of splicing (missplicing) in specific genes and that such misspliced genes might be important in leukemogenesis. We analyzed RNA deep sequencing to compare splicing patterns of 201 837 exons between the cases with U2AF1 mutations (n = 6) and wild type (n = 14). We identified different alternative splicing patterns in 35 genes comparing cells with mutant and wild-type U2AF1. U2AF1 mutations are associated with abnormal splicing of genes involved in functionally important pathways, such as cell cycle progression and RNA processing. In addition, many of these genes are somatically mutated or deleted in various cancers. Of note is that the alternative splicing patterns associated with U2AF1 mutations were associated with specific sequence signals at the affected splice sites. These novel observations support the hypothesis that U2AF1 mutations play a significant role in myeloid leukemogenesis due to selective missplicing of tumor-associated genes. PMID:23775717

  10. SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice

    PubMed Central

    Börjesson, Anna E.; Farman, Helen H.; Movérare-Skrtic, Sofia; Engdahl, Cecilia; Antal, Maria Cristina; Koskela, Antti; Tuukkanen, Juha; Carlsten, Hans; Krust, Andrée; Chambon, Pierre; Sjögren, Klara; Lagerquist, Marie K.; Windahl, Sara H.

    2016-01-01

    The bone-sparing effect of estrogens is mediated primarily via estrogen receptor (ER)α, which stimulates gene transcription through activation function (AF)-1 and AF-2. The role of ERαAF-1 for the estradiol (E2) effects is tissue specific. The selective ER modulators (SERMs) raloxifene (Ral), lasofoxifene (Las), and bazedoxifene (Bza) can be used to treat postmenopausal osteoporosis. They all reduce the risk for vertebral fractures, whereas Las and partly Bza, but not Ral, reduce the risk for nonvertebral fractures. Here, we have compared the tissue specificity of Ral, Las, and Bza and evaluated the role of ERαAF-1 for the effects of these SERMs, with an emphasis on bone parameters. We treated ovariectomized (OVX) wild-type (WT) mice and OVX mice lacking ERαAF-1 (ERαAF-10) with E2, Ral, Las, or Bza. All three SERMs increased trabecular bone mass in the axial skeleton. In the appendicular skeleton, only Las increased the trabecular bone volume/tissue volume and trabecular number, whereas both Ral and Las increased the cortical bone thickness and strength. However, Ral also increased cortical porosity. The three SERMs had only a minor effect on uterine weight. Notably, all evaluated effects of these SERMs were absent in ovx ERαAF-10 mice. In conclusion, all SERMs had similar effects on axial bone mass. However, the SERMs had slightly different effects on the appendicular skeleton since only Las increased the trabecular bone mass and only Ral increased the cortical porosity. Importantly, all SERM effects require a functional ERαAF-1 in female mice. These results could lead to development of more specific treatments for osteoporosis. PMID:27048997

  11. Wild-Type U2AF1 Antagonizes the Splicing Program Characteristic of U2AF1-Mutant Tumors and Is Required for Cell Survival

    PubMed Central

    Fei, Dennis Liang; Motowski, Hayley; Chatrikhi, Rakesh; Gao, Shaojian; Kielkopf, Clara L.; Varmus, Harold

    2016-01-01

    We have asked how the common S34F mutation in the splicing factor U2AF1 regulates alternative splicing in lung cancer, and why wild-type U2AF1 is retained in cancers with this mutation. A human lung epithelial cell line was genetically modified so that U2AF1S34F is expressed from one of the two endogenous U2AF1 loci. By altering levels of mutant or wild-type U2AF1 in this cell line and by analyzing published data on human lung adenocarcinomas, we show that S34F-associated changes in alternative splicing are proportional to the ratio of S34F:wild-type gene products and not to absolute levels of either the mutant or wild-type factor. Preferential recognition of specific 3′ splice sites in S34F-expressing cells is largely explained by differential in vitro RNA-binding affinities of mutant versus wild-type U2AF1 for those same 3′ splice sites. Finally, we show that lung adenocarcinoma cell lines bearing U2AF1 mutations do not require the mutant protein for growth in vitro or in vivo. In contrast, wild-type U2AF1 is required for survival, regardless of whether cells carry the U2AF1S34F allele. Our results provide mechanistic explanations of the magnitude of splicing changes observed in U2AF1-mutant cells and why tumors harboring U2AF1 mutations always retain an expressed copy of the wild-type allele. PMID:27776121

  12. Human PSENEN and U2AF1L4 genes are concertedly regulated by a genuine bidirectional promoter.

    PubMed

    Didych, D A; Shamsutdinov, M F; Smirnov, N A; Akopov, S B; Monastyrskaya, G S; Uspenskaya, N Y; Nikolaev, L G; Sverdlov, E D

    2013-02-15

    Head-to-head genes with a short distance between their transcription start sites may constitute up to 10% of all genes in the genomes of various species. It was hypothesized that this intergenic space may represent bidirectional promoters which are able to initiate transcription of both genes, but the true bidirectionality was proved only for a few of them. We present experimental evidence that, according to several criteria, a 269 bp region located between the PSENEN and U2AF1L4 human genes is a genuine bidirectional promoter regulating a concerted divergent transcription of these genes. Concerted transcription of PSENEN and U2AF1L4 can be necessary for regulation of T-cell activity. PMID:23246698

  13. Mutant U2AF1 Expression Alters Hematopoiesis and Pre-mRNA Splicing In Vivo

    PubMed Central

    Shirai, Cara Lunn; Ley, James N.; White, Brian S.; Kim, Sanghyun; Tibbitts, Justin; Shao, Jin; Ndonwi, Matthew; Wadugu, Brian; Duncavage, Eric J.; Okeyo-Owuor, Theresa; Liu, Tuoen; Griffith, Malachi; McGrath, Sean; Magrini, Vincent; Fulton, Robert S.; Fronick, Catrina; O’Laughlin, Michelle; Graubert, Timothy A.; Walter, Matthew J.

    2015-01-01

    SUMMARY Heterozygous somatic mutations in the spliceosome gene U2AF1 occur in ~11% of patients with myelodysplastic syndromes (MDS), the most common adult myeloid malignancy. It is unclear how these mutations contribute to disease. We examined in vivo hematopoietic consequences of the most common U2AF1 mutation using a doxycycline-inducible transgenic mouse model. Mice expressing mutant U2AF1(S34F) display altered hematopoiesis and changes in pre-mRNA splicing in hematopoietic progenitor cells by whole transcriptome analysis (RNA-seq). Integration with human RNA-seq datasets determined that common mutant U2AF1-induced splicing alterations are enriched in RNA processing genes, ribosomal genes, and recurrently-mutated MDS and acute myeloid leukemia-associated genes. These findings support the hypothesis that mutant U2AF1 alters downstream gene isoform expression, thereby contributing to abnormal hematopoiesis in MDS patients. PMID:25965570

  14. Sintokamide A Is a Novel Antagonist of Androgen Receptor That Uniquely Binds Activation Function-1 in Its Amino-terminal Domain*

    PubMed Central

    Banuelos, Carmen A.; Tavakoli, Iran; Tien, Amy H.; Caley, Daniel P.; Mawji, Nasrin R.; Li, Zhenzhen; Wang, Jun; Yang, Yu Chi; Imamura, Yusuke; Yan, Luping; Wen, Jian Guo; Andersen, Raymond J.; Sadar, Marianne D.

    2016-01-01

    Androgen receptor (AR) is a validated drug target for all stages of prostate cancer including metastatic castration-resistant prostate cancer (CRPC). All current hormone therapies for CRPC target the C-terminal ligand-binding domain of AR and ultimately all fail with resumed AR transcriptional activity. Within the AR N-terminal domain (NTD) is activation function-1 (AF-1) that is essential for AR transcriptional activity. Inhibitors of AR AF-1 would potentially block most AR mechanisms of resistance including constitutively active AR splice variants that lack the ligand-binding domain. Here we provide evidence that sintokamide A (SINT1) binds AR AF-1 region to specifically inhibit transactivation of AR NTD. Consistent with SINT1 targeting AR AF-1, it attenuated transcriptional activities of both full-length AR and constitutively active AR splice variants, which correlated with inhibition of growth of enzalutamide-resistant prostate cancer cells expressing AR splice variants. In vivo, SINT1 caused regression of CRPC xenografts and reduced expression of prostate-specific antigen, a gene transcriptionally regulated by AR. Inhibition of AR activity by SINT1 was additive to EPI-002, a known AR AF-1 inhibitor that is in clinical trials (NCT02606123). This implies that SINT1 binds to a site on AF-1 that is unique from EPI. Consistent with this suggestion, these two compounds showed differences in blocking AR interaction with STAT3. This work provides evidence that the intrinsically disordered NTD of AR is druggable and that SINT1 analogs may provide a novel scaffold for drug development for the treatment of prostate cancer or other diseases of the AR axis. PMID:27576691

  15. The Activation Function-1 of Estrogen Receptor Alpha Prevents Arterial Neointima Development Through a Direct Effect on Smooth Muscle Cells

    PubMed Central

    Smirnova, Natalia F.; Fontaine, Coralie; Buscato, Mélissa; Lupieri, Adrien; Vinel, Alexia; Valera, Marie-Cécile; Guillaume, Maeva; Malet, Nicole; Foidart, Jean-Michel; Raymond-Letron, Isabelle; Lenfant, Francoise; Gourdy, Pierre; Katzenellenbogen, Benita S.; Katzenellenbogen, John A.; Laffargue, Muriel; Arnal, Jean-Francois

    2015-01-01

    Rationale: 17β-Estradiol (E2) exerts numerous beneficial effects in vascular disease. It regulates gene transcription through nuclear estrogen receptor α (ERα) via 2 activation functions, AF1 and AF2, and can also activate membrane ERα. The role of E2 on the endothelium relies on membrane ERα activation, but the molecular mechanisms of its action on vascular smooth muscle cells (VSMCs) are not fully understood. Objective: The aim of this study was to determine which cellular target and which ERα subfunction are involved in the preventive action of E2 on neointimal hyperplasia. Methods and Results: To trigger neointimal hyperplasia of VSMC, we used a mouse model of femoral arterial injury. Cre-Lox models were used to distinguish between the endothelial- and the VSMC-specific actions of E2. The molecular mechanisms underlying the role of E2 were further characterized using both selective ERα agonists and transgenic mice in which the ERαAF1 function had been specifically invalidated. We found that (1) the selective inactivation of ERα in VSMC abrogates the neointimal hyperplasia protection induced by E2, whereas inactivation of endothelial and hematopoietic ERα has no effect; (2) the selective activation of membrane ERα does not prevent neointimal hyperplasia; and (3) ERαAF1 is necessary and sufficient to inhibit postinjury VSMC proliferation. Conclusions: Altogether, ERαAF1-mediated nuclear action is both necessary and sufficient to inhibit postinjury arterial VSMC proliferation, whereas membrane ERα largely regulates the endothelial functions of E2. This highlights the exquisite cell/tissue-specific actions of the ERα subfunctions and helps to delineate the spectrum of action of selective ER modulators. PMID:26316608

  16. Different TBP-associated factors are required for mediating the stimulation of transcription in vitro by the acidic transactivator GAL-VP16 and the two nonacidic activation functions of the estrogen receptor.

    PubMed Central

    Brou, C; Wu, J; Ali, S; Scheer, E; Lang, C; Davidson, I; Chambon, P; Tora, L

    1993-01-01

    The estrogen receptor (ER) contains two nonacidic transcriptional activation functions, AF-1 and AF-2 (formerly TAF-1 and TAF-2). In this study we show that AF-1 and AF-2 are able to stimulate transcription in vitro in a HeLa cell system when fused to the DNA binding domain of the yeast activator GAL4. We also demonstrate that a factor(s) required for the function of the ER AFs is chromatographically separable from a factor(s) necessary for the activity of the acidic activation domain of VP16. Moreover, immunoprecipitation experiments using a monoclonal antibody directed against the TATA box binding protein (TBP) indicate, that these different factors are associated with TBP in distinct TFIID complexes. Images PMID:8441620

  17. The cell-specific activity of the estrogen receptor α may be fine-tuned by phosphorylation-induced structural gymnastics

    PubMed Central

    Gburcik, Valentina; Picard, Didier

    2006-01-01

    The estrogen receptor α (ERα) regulates the transcription of target genes by recruiting coregulator proteins through several domains including the two activation functions AF1 and AF2. The contribution of the N-terminally located AF1 activity is particularly important in differentiated cells, and for ERα to integrate inputs from other signaling pathways. However, how the phosphorylation of key residues influences AF1 activity has long remained mysterious, in part because the naturally disordered AF1 domain has resisted a structural characterization. The recent discovery of two coregulators that are specific for a phosphorylated form of AF1 suggests that phosphorylation, possibly in conjunction with the subsequent binding of these coregulators, may enforce a stable structure. The binding of the "pioneer" coregulators might facilitate the subsequent recruitment of yet other coregulators. Different AF1 folds may be enabled by the combinatorial action of posttranslational modifications and coregulator binding thereby fine-tuning ERα activities in a cell- and promoter-specific fashion. PMID:16604168

  18. Identification of the functional domains of ANT-1, a novel coactivator of the androgen receptor

    SciTech Connect

    Fan Shuli; Goto, Kiminobu; Chen Guangchun; Morinaga, Hidetaka; Nomura, Masatoshi; Okabe, Taijiro; Nawata, Hajime; Yanase, Toshihiko . E-mail: yanase@intmed3.med.kyushu-u.ac.jp

    2006-03-03

    Previously, we identified a transcriptional coactivator for the activation function-1 (AF-1) domain of the human androgen receptor (AR) and designated it androgen receptor N-terminal domain transactivating protein-1 (ANT-1). This coactivator, which contains multiple tetratricopeptide repeat (TPR) motifs from amino acid (aa) 294, is identical to a component of U5 small nuclear ribonucleoprotein particles and binds specifically to the AR or glucocorticoid receptor. Here, we identified four distinct functional domains. The AR-AF-1-binding domain, which bound to either aa 180-360 or 360-532 in AR-AF-1, clearly overlapped with TAU-1 and TAU-5. This domain and the subnuclear speckle formation domain in ANT-1 were assigned within the TPR motifs, while the transactivating and nuclear localization signal domains resided within the N-terminal sequence. The existence of these functional domains may further support the idea that ANT-1 can function as an AR-AF-1-specific coactivator while mediating a transcription-splicing coupling.

  19. 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.

  20. DNA Methylation Is Linked to Deacetylation of Histone H3, but Not H4, on the Imprinted Genes Snrpn and U2af1-rs1

    PubMed Central

    Gregory, Richard I.; Randall, Tamzin E.; Johnson, Colin A.; Khosla, Sanjeev; Hatada, Izuho; O'Neill, Laura P.; Turner, Bryan M.; Feil, Robert

    2001-01-01

    The relationship between DNA methylation and histone acetylation at the imprinted mouse genes U2af1-rs1 and Snrpn is explored by chromatin immunoprecipitation (ChIP) and resolution of parental alleles using single-strand conformational polymorphisms. The U2af1-rs1 gene lies within a differentially methylated region (DMR), while Snrpn has a 5′ DMR (DMR1) with sequences homologous to the imprinting control center of the Prader-Willi/Angelman region. For both DMR1 of Snrpn and the 5′ untranslated region (5′-UTR) and 3′-UTR of U2af1-rs1, the methylated and nonexpressed maternal allele was underacetylated, relative to the paternal allele, at all H3 lysines tested (K14, K9, and K18). For H4, underacetylation of the maternal allele was exclusively (U2af1-rs1) or predominantly (Snrpn) at lysine 5. Essentially the same patterns of differential acetylation were found in embryonic stem (ES) cells, embryo fibroblasts, and adult liver from F1 mice and in ES cells from mice that were dipaternal or dimaternal for U2af1-rs1. In contrast, in a region within Snrpn that has biallelic methylation in the cells and tissues analyzed, the paternal (expressed) allele showed relatively increased acetylation of H4 but not of H3. The methyl-CpG-binding-domain (MBD) protein MeCP2 was found, by ChIP, to be associated exclusively with the maternal U2af1-rs1 allele. To ask whether DNA methylation is associated with histone deacetylation, we produced mice with transgene-induced methylation at the paternal allele of U2af1-rs1. In these mice, H3 was underacetylated across both the parental U2af1-rs1 alleles whereas H4 acetylation was unaltered. Collectively, these data are consistent with the hypothesis that CpG methylation leads to deacetylation of histone H3, but not H4, through a process that involves selective binding of MBD proteins. PMID:11463825

  1. Inactive allele-specific methylation and chromatin structure of the imprinted gene U2af1-rs1 on mouse chromosome 11

    SciTech Connect

    Shibata, Hideo; Yoshino, Kiyoshi; Kamiya, Mamoru

    1996-07-01

    The imprinted U2Af1-rs1 gene that maps to mouse chromosome 11 is predominately expressed from the paternal allele. We examined the methylation of genomic sequences in and around the U2af1-rs1 locus to establish the extent of sequence modifications that accompanied the silencing of the maternal allele. The analysis of HapII or HhaI sites showed that the silent maternal allele was hypermethylated in a block of CpG sequences that covered more than 10 kb. By comparison, the expressed paternal allele was unmethylated from a CpG island upstream of the transcribed region through 2 kb. An analysis of DNaseI hypersensitivity of a putative promoter of U2af1-rs1 showed an open chromatin conformation only on the unmethylated, expressed paternal allele. These results suggest that allele-specific hypermethylation covering the gene and its upstream CpG island plays a role in maternal allele repression of U2af1-rs1, which is reflected in altered chromatin conformation of DNaseI hypersensitive sites. 9 refs., 2 figs.

  2. Alteration of the SETBP1 Gene and Splicing Pathway Genes SF3B1, U2AF1, and SRSF2 in Childhood Acute Myeloid Leukemia

    PubMed Central

    Choi, Hyun-Woo; Kim, Hye-Ran; Baek, Hee-Jo; Kook, Hoon; Cho, Duck; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook

    2015-01-01

    Background Recurrent somatic SET-binding protein 1 (SETBP1) and splicing pathway gene mutations have recently been found in atypical chronic myeloid leukemia and other hematologic malignancies. These mutations have been comprehensively analyzed in adult AML, but not in childhood AML. We investigated possible alteration of the SETBP1, splicing factor 3B subunit 1 (SF3B1), U2 small nuclear RNA auxiliary factor 1 (U2AF1), and serine/arginine-rich splicing factor 2 (SRSF2) genes in childhood AML. Methods Cytogenetic and molecular analyses were performed to reveal chromosomal and genetic alterations. Sequence alterations in the SETBP1, SF3B1, U2AF1, and SRSF2 genes were examined by using direct sequencing in a cohort of 53 childhood AML patients. Results Childhood AML patients did not harbor any recurrent SETBP1 gene mutations, although our study did identify a synonymous mutation in one patient. None of the previously reported aberrations in the mutational hotspot of SF3B1, U2AF1, and SRSF2 were identified in any of the 53 patients. Conclusions Alterations of the SETBP1 gene or SF3B1, U2AF1, and SRSF2 genes are not common genetic events in childhood AML, implying that the mutations are unlikely to exert a driver effect in myeloid leukemogenesis during childhood. PMID:25553291

  3. Obstacles to activity pacing: assessment, relationship to activity and functioning.

    PubMed

    Cane, Douglas; McCarthy, Mary; Mazmanian, Dwight

    2016-07-01

    Activity pacing is frequently included among the strategies provided to individuals with chronic pain to manage pain and improve functioning. Individuals with chronic pain may, however, limit their use of activity pacing because they perceive significant obstacles to its use. This study describes the development of a measure to assess obstacles to activity pacing and examines the relationship of this measure to activity patterns and functioning. A sample of 637 individuals with chronic pain completed items describing potential obstacles to activity pacing as part of their pretreatment assessment. Item analyses were used to construct a 14-item measure of obstacles to activity pacing. A subset of these individuals completed the measure again after completion of a group treatment program. The resulting measure demonstrated excellent internal consistency and was minimally affected by social desirability. Correlations with measures of activity and psychosocial functioning provided initial construct validity for the measure. Sex differences were found with women initially identifying more obstacles to activity pacing. Fewer obstacles were identified by both men and women after treatment, and these changes were related to modest changes in activity patterns and functioning. The present results identify a number of obstacles that may limit the use of activity pacing by individuals with chronic pain. Treatment may result in a decrease in the number of obstacles identified, and this change is related to changes in the individual's activity pattern and psychosocial functioning. PMID:26963845

  4. Contractile Function During Angiotensin-II Activation

    PubMed Central

    Zhang, Min; Prosser, Benjamin L.; Bamboye, Moradeke A.; Gondim, Antonio N.S.; Santos, Celio X.; Martin, Daniel; Ghigo, Alessandra; Perino, Alessia; Brewer, Alison C.; Ward, Christopher W.; Hirsch, Emilio; Lederer, W. Jonathan; Shah, Ajay M.

    2015-01-01

    Background Renin-angiotensin system activation is a feature of many cardiovascular conditions. Activity of myocardial reduced nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2 or Nox2) is enhanced by angiotensin II (Ang II) and contributes to increased hypertrophy, fibrosis, and adverse remodeling. Recent studies found that Nox2-mediated reactive oxygen species production modulates physiological cardiomyocyte function. Objectives This study sought to investigate the effects of cardiomyocyte Nox2 on contractile function during increased Ang II activation. Methods We generated a cardiomyocyte-targeted Nox2-transgenic mouse model and studied the effects of in vivo and ex vivo Ang II stimulation, as well as chronic aortic banding. Results Chronic subpressor Ang II infusion induced greater cardiac hypertrophy in transgenic than wild-type mice but unexpectedly enhanced contractile function. Acute Ang II treatment also enhanced contractile function in transgenic hearts in vivo and transgenic cardiomyocytes ex vivo. Ang II–stimulated Nox2 activity increased sarcoplasmic reticulum (SR) Ca2+ uptake in transgenic mice, increased the Ca2+ transient and contractile amplitude, and accelerated cardiomyocyte contraction and relaxation. Elevated Nox2 activity increased phospholamban phosphorylation in both hearts and cardiomyocytes, related to inhibition of protein phosphatase 1 activity. In a model of aortic banding–induced chronic pressure overload, heart function was similarly depressed in transgenic and wild-type mice. Conclusions We identified a novel mechanism in which Nox2 modulates cardiomyocyte SR Ca2+ uptake and contractile function through redox-regulated changes in phospholamban phosphorylation. This mechanism can drive increased contractility in the short term in disease states characterized by enhanced renin-angiotensin system activation. PMID:26184620

  5. Functional activity monitoring from wearable sensor data.

    PubMed

    Nawab, S Hamid; Roy, Serge H; De Luca, Carlo J

    2004-01-01

    A novel approach is presented for the interpretation and use of EMG and accelerometer data to monitor, identify, and categorize functional motor activities in individuals whose movements are unscripted, unrestrained, and take place in the "real world". Our proposed solution provides a novel and practical way of conceptualizing physical activities that facilitates the deployment of modern signal processing and interpretation techniques to carry out activity monitoring. A hierarchical approach is adopted that is based upon: 1) blackboard and rule-based technology from artificial intelligence to support a process in which coarse-grained activity partitioning forms the context for finer-grained activity partitioning; 2) neural network technology to support initial activity classification; and 3) integrated processing and understanding of signals (IPUS) technology for revising the initial classifications to account for the high degrees of anticipated signal variability and overlap during freeform activity. PMID:17271844

  6. Integrating Communication Skills into Functional Routines & Activities.

    ERIC Educational Resources Information Center

    Stremel, Kathleen

    This training module on integrating communication skills into functional routines and activities is from the Mississippi Early Education Program for Children with Multiple Disabilities, a program designed to train Individuals with Disabilities Education Act Part H service coordinators and service providers to use family centered strategies. The…

  7. 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.

  8. Dosage of the Abcg1-U2af1 region modifies locomotor and cognitive deficits observed in the Tc1 mouse model of Down syndrome.

    PubMed

    Marechal, Damien; Lopes Pereira, Patricia; Duchon, Arnaud; Herault, Yann

    2015-01-01

    Down syndrome (DS) results from one extra copy of human chromosome 21 and leads to several alterations including intellectual disabilities and locomotor defects. The transchromosomic Tc1 mouse model carrying an extra freely-segregating copy of human chromosome 21 was developed to better characterize the relation between genotype and phenotype in DS. The Tc1 mouse exhibits several locomotor and cognitive deficits related to DS. In this report we analyzed the contribution of the genetic dosage of 13 conserved mouse genes located between Abcg1 and U2af1, in the telomeric part of Hsa21. We used the Ms2Yah model carrying a deletion of the corresponding interval in the mouse genome to rescue gene dosage in the Tc1/Ms2Yah compound mice to determine how the different behavioral phenotypes are affected. We detected subtle changes with the Tc1/Ms2Yah mice performing better than the Tc1 individuals in the reversal paradigm of the Morris water maze. We also found that Tc1/Ms2Yah compound mutants performed better in the rotarod than the Tc1 mice. This data support the impact of genes from the Abcg1-U2af1 region as modifiers of Tc1-dependent memory and locomotor phenotypes. Our results emphasize the complex interactions between triplicated genes inducing DS features.

  9. 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

  10. Functional Stability of Plasminogen Activator Inhibitor-1

    PubMed Central

    Kuru, Pinar; Toksoy Oner, Ebru; Agirbasli, Mehmet

    2014-01-01

    Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of plasminogen activators, such as tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), and a major regulator of the fibrinolytic system. PAI-1 plays a pivotal role in acute thrombotic events such as deep vein thrombosis (DVT) and myocardial infarction (MI). The biological effects of PAI-1 extend far beyond thrombosis including its critical role in fibrotic disorders, atherosclerosis, renal and pulmonary fibrosis, type-2 diabetes, and cancer. The conversion of PAI-1 from the active to the latent conformation appears to be unique among serpins in that it occurs spontaneously at a relatively rapid rate. Latency transition is believed to represent a regulatory mechanism, reducing the risk of thrombosis from a prolonged antifibrinolytic action of PAI-1. Thus, relying solely on plasma concentrations of PAI-1 without assessing its function may be misleading in interpreting the role of PAI-1 in many complex diseases. Environmental conditions, interaction with other proteins, mutations, and glycosylation are the main factors that have a significant impact on the stability of the PAI-1 structure. This review provides an overview on the current knowledge on PAI-1 especially importance of PAI-1 level and stability and highlights the potential use of PAI-1 inhibitors for treating cardiovascular disease. PMID:25386620

  11. 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

  12. Phagocytic cell function in active brucellosis.

    PubMed Central

    Ocon, P; Reguera, J M; Morata, P; Juarez, C; Alonso, A; Colmenero, J D

    1994-01-01

    In this study, we analyzed phagocytic cell function in 51 patients with active brucellosis and its relationship with different clinical, serological, and evolutionary variables. A control group was made up of 30 blood donors of similar geographic extraction, age, and sex, with no previous history of brucellosis or known exposure ot the infection or specific antibodies. The investigations were carried out at the time of diagnosis, at the conclusion of treatment, and after 6 months of follow-up. Polymorphonuclear leukocyte adherence and nitroblue tetrazolium reduction in response to Brucella antigen were significantly increased in the patients at the time of diagnosis with respect to the control group. In contrast, chemotaxis in response to Brucella antigen and phagocytosis were significantly reduced in the patients with respect to the control group. The alterations in phagocytic cell function were greater in patients with bacteremia, with focal forms of the disease, or with a longer diagnostic delay. Most of these initial alterations tended to normalize with treatment, indicating their transient character. PMID:8112863

  13. The gene for human U2 snRNP auxiliary factor small 35-kDa subunit (U2AF1) maps to the progressive myoclonus epilepsy (EPM1) critical region on chromosome 21q22.3

    SciTech Connect

    Lalioti, M.D.; Rossier, C.; Antonarakis, S.E.

    1996-04-15

    We used targeted exon trapping to clone portions of genes from human chromosome 21q22.3. One trapped sequence showed complete homology with the cDNA of human U2AF{sup 35} (M96982; HGM-approved nomenclature U2AF1), which encodes for the small 35-kDa subunit of the U2 snRNP auxiliary factor. Using the U2AF1 cDNA as a probe, we mapped this gene to cosmid Q15D2, a P1, and YAC 350F7 of the Chumakov et al. contig, close to the cystathionine-{beta}-synthase gene (CBS) on 21q22.3. This localization was confirmed by PCR using oligonucleotides from the 3{prime} UTR and by FISH. As U2AF1 associated with a number of different factors during mRNA splicing, overexpression in trisomy 21 individuals could contribute to some Down syndrome phenotypes by interfering with the splicing process. Furthermore, because this gene maps in the critical region for the progressive myoclonus epilepsy I locus (EPM1), mutation analysis will be carried out in patients to evaluate the potential role of U2AF1 as a candidate for EPM1. 24 refs., 1 fig.

  14. An imaging agent to detect androgen receptor and its active splice variants in prostate cancer

    PubMed Central

    Imamura, Yusuke; Tien, Amy H.; Pan, Jinhe; Leung, Jacky K.; Banuelos, Carmen A.; Jian, Kunzhong; Wang, Jun; Mawji, Nasrin R.; Fernandez, Javier Garcia; Lin, Kuo-Shyan; Andersen, Raymond J.; Sadar, Marianne D.

    2016-01-01

    Constitutively active splice variants of androgen receptor (AR-Vs) lacking ligand-binding domain (LBD) are a mechanism of resistance to androgen receptor LBD–targeted (AR LBD–targeted) therapies for metastatic castration-resistant prostate cancer (CRPC). There is a strong unmet clinical need to identify prostate cancer patients with AR-V–positive lesions to determine whether they will benefit from further AR LBD–targeting therapies or should receive taxanes or investigational drugs like EPI-506 or galeterone. Both EPI-506 (NCT02606123) and galeterone (NCT02438007) are in clinical trials and are proposed to have efficacy against lesions that are positive for AR-Vs. AR activation function-1 (AF-1) is common to the N-terminal domains of full-length AR and AR-Vs. Here, we provide proof of concept for developing imaging compounds that directly bind AR AF-1 to detect both AR-Vs and full-length AR. 123I-EPI-002 had specific binding to AR AF-1, which enabled direct visualization of CRPC xenografts that express full-length AR and AR-Vs. Our findings highlight the potential of 123I-EPI-002 as an imaging agent for the detection of full-length AR and AR-Vs in CRPC. PMID:27525313

  15. Genome-wide Association Study Identifies TNFSF15 and POU2AF1 as Susceptibility Loci for Primary Biliary Cirrhosis in the Japanese Population

    PubMed Central

    Nakamura, Minoru; Nishida, Nao; Kawashima, Minae; Aiba, Yoshihiro; Tanaka, Atsushi; Yasunami, Michio; Nakamura, Hitomi; Komori, Atsumasai; Nakamuta, Makoto; Zeniya, Mikio; Hashimoto, Etsuko; Ohira, Hiromasa; Yamamoto, Kazuhide; Onji, Morikazu; Kaneko, Shuichi; Honda, Masao; Yamagiwa, Satoshi; Nakao, Kazuhiko; Ichida, Takafumi; Takikawa, Hajime; Seike, Masataka; Umemura, Takeji; Ueno, Yoshiyuki; Sakisaka, Shotaro; Kikuchi, Kentaro; Ebinuma, Hirotoshi; Yamashiki, Noriyo; Tamura, Sumito; Sugawara, Yasuhiko; Mori, Akira; Yagi, Shintaro; Shirabe, Ken; Taketomi, Akinobu; Arai, Kuniaki; Monoe, Kyoko; Ichikawa, Tatsuki; Taniai, Makiko; Miyake, Yasuhiro; Kumagi, Teru; Abe, Masanori; Yoshizawa, Kaname; Joshita, Satoru; Shimoda, Shinji; Honda, Koichi; Takahashi, Hiroki; Hirano, Katsuji; Takeyama, Yasuaki; Harada, Kenichi; Migita, Kiyoshi; Ito, Masahiro; Yatsuhashi, Hiroshi; Fukushima, Nobuyoshi; Ota, Hajime; Komatsu, Tatsuji; Saoshiro, Takeo; Ishida, Jinya; Kouno, Hirotsugu; Kouno, Hirotaka; Yagura, Michiyasu; Kobayashi, Masakazu; Muro, Toyokichi; Masaki, Naohiko; Hirata, Keiichi; Watanabe, Yukio; Nakamura, Yoko; Shimada, Masaaki; Hirashima, Noboru; Komeda, Toshiki; Sugi, Kazuhiro; Koga, Michiaki; Ario, Keisuke; Takesaki, Eiichi; Maehara, Yoshihiko; Uemoto, Shinji; Kokudo, Norihiro; Tsubouchi, Hirohito; Mizokami, Masashi; Nakanuma, Yasuni; Tokunaga, Katsushi; Ishibashi, Hiromi

    2012-01-01

    For the identification of susceptibility loci for primary biliary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 × 10−14 for rs4979462, and combined OR = 1.39, p = 2.38 × 10−8 for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 × 10−8, 3.66 × 10−9, and 3.04 × 10−9, respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 × 10−6 and 1.42 × 10−7, respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals. PMID:23000144

  16. Function of streptokinase fragments in plasminogen activation.

    PubMed Central

    Shi, G Y; Chang, B I; Chen, S M; Wu, D H; Wu, H L

    1994-01-01

    Several peptide fragments of streptokinase (SK) were prepared by incubating SK with immobilized human plasmin (hPlm) and purified by h.p.l.c. with a reverse-phase phenyl column. The N-terminal sequences, amino acid compositions and molecular masses of these peptide fragments were determined. The SK peptide fragment of 36 kDa consisting of Ser60-Lys387 (SK-p), was the only peptide fragment that could be tightly bound to immobilized hPlm. Another three large SK peptide fragments, SK-m, SK-n and SK-o, with molecular masses of 7 kDa, 18 kDa and 30 kDa, and consisting of Ile1-Lys59, Glu148-Lys333, Ser60-Lys333 respectively, were also obtained from the supernatant of the reaction mixture. The purified SK-p had high affinity with hPlm and could activate human plasminogen (hPlg) with a kPlg one-sixth that of the native SK. SK-o had low affinity with hPlm and could also activate hPlg, although the catalytic constant was less than 1% of the native SK. SK-n, as well as SK-m, which is the N-terminal 59 amino acid peptide of the native SK, had no activator activity. However, SK-m could enhance the activator activity of both SK-o and SK-p and increase their second-order rate constants by two- and six-fold respectively. It was concluded from these studies that (1) SK-o, the Ser60-Lys333 peptide of SK, was essential for minimal SK activator activity, (2) the C-terminal peptide of SK-p, Ala334-Lys387, was essential for high affinity with hPlm, and (3) the N-terminal 59-amino-acid peptide was important in maintaining the proper conformation of SK to have its full activator activity. Images Figure 1 Figure 2 PMID:7998939

  17. Constructive feedforward neural networks using hermite polynomial activation functions.

    PubMed

    Ma, Liying; Khorasani, K

    2005-07-01

    In this paper, a constructive one-hidden-layer network is introduced where each hidden unit employs a polynomial function for its activation function that is different from other units. Specifically, both a structure level as well as a function level adaptation methodologies are utilized in constructing the network. The functional level adaptation scheme ensures that the "growing" or constructive network has different activation functions for each neuron such that the network may be able to capture the underlying input-output map more effectively. The activation functions considered consist of orthonormal Hermite polynomials. It is shown through extensive simulations that the proposed network yields improved performance when compared to networks having identical sigmoidal activation functions.

  18. 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.

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

    NASA Astrophysics Data System (ADS)

    Sathasivam, Saratha

    2010-12-01

    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.

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... programmatic activity costs? 641.864 Section 641.864 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION... Requirements § 641.864 What functions and activities constitute programmatic activity costs? Programmatic activity costs include, but are not limited to, the costs of the following functions: (a) Participant...

  1. New approaches to enhance active steering system functionalities: preliminary results

    NASA Astrophysics Data System (ADS)

    Serarslan, Benan

    2014-09-01

    An important development of the steering systems in general is active steering systems like active front steering and steer-by-wire systems. In this paper the current functional possibilities in application of active steering systems are explored. A new approach and additional functionalities are presented that can be implemented to the active steering systems without additional hardware such as new sensors and electronic control units. Commercial active steering systems are controlling the steering angle depending on the driving situation only. This paper introduce methods for enhancing active steering system functionalities depending not only on the driving situation but also vehicle parameters like vehicle mass, tyre and road condition. In this regard, adaptation of the steering ratio as a function of above mentioned vehicle parameters is presented with examples. With some selected vehicle parameter changes, the reduction of the undesired influences on vehicle dynamics of these parameter changes has been demonstrated theoretically with simulations and with real-time driving measurements.

  2. Acceleration of reverse analysis method using hyperbolic activation function

    NASA Astrophysics Data System (ADS)

    Pwasong, Augustine; Sathasivam, Saratha

    2015-10-01

    Hyperbolic activation function is examined for its ability to accelerate the performance of doing data mining by using a technique named as Reverse Analysis method. In this paper, we describe how Hopfield network perform better with hyperbolic activation function and able to induce logical rules from large database by using reverse analysis method: given the values of the connections of a network, we can hope to know what logical rules are entrenched in the database. We limit our analysis to Horn clauses.

  3. STUDENT ACTIVITIES STAFF FUNCTIONS--SUM AND SUBSTANCE.

    ERIC Educational Resources Information Center

    MARINE, JAMES

    THIS STUDY WAS DESIGNED TO ASSESS (1) THE CURRENT STATUS OF STUDENT ACTIVITIES (S.A.) WORK, (2) THE PERSONS ASSUMING MAJOR RESPONSIBILITY FOR THE S.A. FUNCTION AND THEIR CHARACTERISTICS, BACKGROUND, AND GOALS, (3) THE FUNCTIONS OF PERSONS WHO TAKE LEADERSHIP FOR S.A. PROGRAMS, AND (4) THE TRENDS AND DEVELOPMENTS IN S.A. COPIES OF A FIVE-PAGE…

  4. 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

  5. A current type PWM rectifier with active damping function

    SciTech Connect

    Sato, Yukihiko; Kataoka, Teruo

    1995-12-31

    A new control method for current type PWM rectifiers which can provide active damping function is presented. This damping function is effective only on the harmonic components of ac input current selectively. Thus steady state waveform distortion and transient oscillation of the input current are reduced by the active damping effects. The active damping function can be realized by feed-back control of an LC filter connected to the ac side of the rectifier, and it does not require any additional components in the main circuits, permitting a simple circuit configuration. The control system of the proposed PWM rectifier is analyzed by using a simple block diagram developed in the present paper. From the analytical results, the influence of the circuit parameters and control delay on the active damping effects and the stability of the operation is clarified to establish the design method. To confirm the effectiveness of the active damping function, some results of basic experiments are included. As an example of application of the active damping function, the proposed rectifier is applied to reduce the harmonic currents generated by conventional rectifiers operating in parallel with the proposed rectifier. Some experimental results in this application are also included.

  6. A current-type PWM rectifier with active damping function

    SciTech Connect

    Sato, Yukihiko; Kataoka, Teruo

    1996-05-01

    A new control method for current-type pulse-width modulation (PWM) rectifiers which can provide active damping function is presented. This damping function is effective only on the harmonic components of ac input current selectively. Thus steady-state waveform distortion and transient oscillation of the input current are reduced by the active damping effects. The active damping function can be realized by feedback control of an LC filter connected to the ac side of the rectifier, and it does not require any additional components in the main circuits, permitting a simple circuit configuration. The control system of the proposed PWM rectifier is analyzed by using a simple block diagram developed in the present paper. From the analytical results, the influence of the circuit parameters and control delay on the active damping effects and the stability of the operation are clarified to establish the design method. To confirm the effectiveness of the active damping function, some results of basic experiments are included. As an example of application of the active damping function, the proposed rectifier is applied to reduce the harmonic currents generated by conventional rectifiers operating in parallel with the proposed rectifier. Some experimental results in this application are also included.

  7. 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.

  8. Geometrical modulation transfer function for different pixel active area shapes

    NASA Astrophysics Data System (ADS)

    Yadid-Pecht, Orly

    2000-04-01

    In this work we consider the effect of the pixel active area geometrical shape on the modulation transfer function (MTF) of an image sensor. When designing a CMOS Active Pixel Sensor, or a CCD or CID sensor for this matter, the active area of the pixel would have a certain geometrical shape which might not cover the whole pixel area. To improve the device performance, it is important to understand the effect this has on the pixel sensitivity and on the resulting MTF. We perform a theoretical analysis of the MTF for the active area shape and derive explicit formulas for the transfer function for pixel arrays with a square, a rectangular and an L shaped active area (most commonly used), and generalize for any connected active area shape. Preliminary experimental results of subpixel scanning sensitivity maps and the corresponding MTFs have also bee obtained, which confirm the theoretical derivations. Both the simulation results and the MTF calculated from the point spread function measurements of the actual pixel arrays show that the active area shape contributes significantly to the behavior of the overall MTF. The results also indicate that for any potential pixel active area shape, the effect of its diversion from the square pixel could be calculated, so that tradeoff between the conflicting requirements, such as SNR and MTF, could be compared per each pixel design for better overall sensor performance.

  9. Berberine Improves Kidney Function in Diabetic Mice via AMPK Activation

    PubMed Central

    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. PMID:25409232

  10. 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.

  11. 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.

  12. 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

  13. Model of local temperature changes in brain upon functional activation.

    PubMed

    Collins, Christopher M; Smith, Michael B; Turner, Robert

    2004-12-01

    Experimental results for changes in brain temperature during functional activation show large variations. It is, therefore, desirable to develop a careful numerical model for such changes. Here, a three-dimensional model of temperature in the human head using the bioheat equation, which includes effects of metabolism, perfusion, and thermal conduction, is employed to examine potential temperature changes due to functional activation in brain. It is found that, depending on location in brain and corresponding baseline temperature relative to blood temperature, temperature may increase or decrease on activation and concomitant increases in perfusion and rate of metabolism. Changes in perfusion are generally seen to have a greater effect on temperature than are changes in metabolism, and hence active brain is predicted to approach blood temperature from its initial temperature. All calculated changes in temperature for reasonable physiological parameters have magnitudes <0.12 degrees C and are well within the range reported in recent experimental studies involving human subjects.

  14. Neural progenitor cells regulate microglia functions and activity.

    PubMed

    Mosher, Kira I; Andres, Robert H; Fukuhara, Takeshi; Bieri, Gregor; Hasegawa-Moriyama, Maiko; He, Yingbo; Guzman, Raphael; Wyss-Coray, Tony

    2012-11-01

    We found mouse neural progenitor cells (NPCs) to have a secretory protein profile distinct from other brain cells and to modulate microglial activation, proliferation and phagocytosis. NPC-derived vascular endothelial growth factor was necessary and sufficient to exert at least some of these effects in mice. Thus, neural precursor cells may not only be shaped by microglia, but also regulate microglia functions and activity.

  15. 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.

  16. 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

  17. 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.

  18. [Significance of the functional activity of antibodies in influenza immunity].

    PubMed

    Naĭkhin, A N; Artem'eva, S A; Bosak, L V; Katorgina, L G

    1995-01-01

    A simple and inexpensive test for mass examination of the functional activity of serum antibodies was developed. The test is based on a kinetic serologic reaction that reflects the time course of changes in antibody titers depending on the time of contact of the tested material with antigen. The curves of serum kinetic titration were processed on a computer by the special programme. As a result, an integral factor, an antibody functional activity index (AFAI) was calculated for each serum sample under study. The titers and AFAI were determined in more than 2,000 healthy persons, patients with influenza A and B, and those immunized with different influenza vaccines. The persons having similar antibody titers were demonstrated to greatly differ in AFAI. The functional activity of antibodies is a more precise marker of protection from influenza than the routine quantitative characteristics of antibodies, i.e. titers. The high baseline AFAI decreased the severity of influenza infection. Live influenza vaccines stimulated the production of antibodies having higher AFAI than inactivated ones. The live influenza strains (candidates for vaccine ones) significantly differed in their ability to stimulate the production of antibodies having a high functional activity.

  19. 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.

  20. Functional constituents of the active site of human neutrophil collagenase.

    PubMed

    Mookhtiar, K A; Wang, F; Van Wart, H E

    1986-05-01

    A series of chemical modification reactions has been carried out to identify functional constituents of the active site of human neutrophil collagenase. The enzyme is reversibly inhibited by the transition metal chelating agent 1,10-phenanthroline, and inhibition is fully reversed by zinc. Removal of weakly bound metal ions by gel filtration inactivates collagenase, and activity is fully restored on immediate readdition of calcium. The enzyme is unaffected by reagents that modify serine, cysteine, and arginine residues. However, reaction with the carboxyl reagents cyclohexylmorpholinocarbodiimide and Woodward's Reagent K lowers the activity of the enzyme substantially. Acetylimidazole inactivates the enzyme, but activity is completely restored on addition of hydroxylamine. The enzyme is also inactivated by tetranitromethane, indicating that it contains an essential tyrosine residue. Acylation of collagenase with diethyl pyrocarbonate, diketene, acetic anhydride, or trinitrobenzenesulfonate inactivates the enzyme, and activity is not restored on addition of hydroxylamine, indicating the presence of an essential lysine residue.

  1. Angiotensin-converting enzyme 2 activation improves endothelial function.

    PubMed

    Fraga-Silva, Rodrigo A; Costa-Fraga, Fabiana P; Murça, Tatiane M; Moraes, Patrícia L; Martins Lima, Augusto; Lautner, Roberto Q; Castro, Carlos H; Soares, Célia Maria A; Borges, Clayton L; Nadu, Ana Paula; Oliveira, Marilene L; Shenoy, Vinayak; Katovich, Michael J; Santos, Robson A S; Raizada, Mohan K; Ferreira, Anderson J

    2013-06-01

    Diminished release and function of endothelium-derived nitric oxide coupled with increases in reactive oxygen species production is critical in endothelial dysfunction. Recent evidences have shown that activation of the protective axis of the renin-angiotensin system composed by angiotensin-converting enzyme 2, angiotensin-(1-7), and Mas receptor promotes many beneficial vascular effects. This has led us to postulate that activation of intrinsic angiotensin-converting enzyme 2 would improve endothelial function by decreasing the reactive oxygen species production. In the present study, we tested 1-[[2-(dimetilamino)etil]amino]-4-(hidroximetil)-7-[[(4-metilfenil)sulfonil]oxi]-9H-xantona-9 (XNT), a small molecule angiotensin-converting enzyme 2 activator, on endothelial function to validate this hypothesis. In vivo treatment with XNT (1 mg/kg per day for 4 weeks) improved the endothelial function of spontaneously hypertensive rats and of streptozotocin-induced diabetic rats when evaluated through the vasorelaxant responses to acetylcholine/sodium nitroprusside. Acute in vitro incubation with XNT caused endothelial-dependent vasorelaxation in aortic rings of rats. This vasorelaxation effect was attenuated by the Mas antagonist D-pro7-Ang-(1-7), and it was reduced in Mas knockout mice. These effects were associated with reduction in reactive oxygen species production. In addition, Ang II-induced reactive oxygen species production in human aortic endothelial cells was attenuated by preincubation with XNT. These results showed that chronic XNT administration improves the endothelial function of hypertensive and diabetic rat vessels by attenuation of the oxidative stress. Moreover, XNT elicits an endothelial-dependent vasorelaxation response, which was mediated by Mas. Thus, this study indicated that angiotensin-converting enzyme 2 activation promotes beneficial effects on the endothelial function and it is a potential target for treating cardiovascular disease.

  2. 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.

  3. 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

  4. 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.

  5. Immunomodulation of phloretin by impairing dendritic cell activation and function.

    PubMed

    Lin, Chi-Chen; Chu, Ching-Liang; Ng, Chin-Sheng; Lin, Ching-Yen; Chen, Der-Yuan; Pan, I-Hong; Huang, Kao-Jean

    2014-05-01

    Dietary compounds in fruits and vegetables have been shown to exert many biological activities. In addition to antioxidant effects, a number of flavonoids are able to modulate inflammatory responses. Here, we demonstrated that phloretin (PT), a natural dihydrochalcone found in many fruits, suppressed the activation and function of mouse dendritic cells (DCs). Phloretin disturbed the multiple intracellular signaling pathways in DCs induced by the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS), including ROS, MAPKs (ERK, JNK, p38 MAPK), and NF-κB, and thereby reducing the production of inflammatory cytokines and chemokines. Phloretin also effectively suppressed the activation of DCs treated with different dosages of LPS or various TLR agonists. The LPS-induced DC maturation was attenuated by phloretin because the expression levels of the MHC class II and the co-stimulatory molecules were down-regulated, which then inhibited the LPS-stimulating DCs and the subsequent naïve T cell activation in a mixed lymphocyte reaction. Moreover, in vivo administration of phloretin suppressed the phenotypic maturation of the LPS-challenged splenic DCs and decreased the IFN-γ production from the activated CD4 T cells. Thus, we suggest that phloretin may potentially be an immunomodulator by impairing the activation and function of DCs and phloretin-contained fruits may be helpful in the improvement of inflammation and autoimmune diseases. PMID:24651121

  6. 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. PMID:26923794

  7. 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

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

    PubMed

    Karan, Ram; Capes, Melinda D; Dassarma, Shiladitya

    2012-02-02

    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.

  9. 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.

  10. 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.

  11. 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. PMID:27482886

  12. 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

    2015-08-01

    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).

  13. Pressure is not a state function for generic active fluids

    NASA Astrophysics Data System (ADS)

    Solon, A. P.; Fily, Y.; Baskaran, A.; Cates, M. E.; Kafri, Y.; Kardar, M.; Tailleur, J.

    2015-08-01

    Pressure is the mechanical force per unit area that a confined system exerts on its container. In thermal equilibrium, it depends only on bulk properties--such as density and temperature--through an equation of state. Here we show that in a wide class of active systems the pressure depends on the precise interactions between the active particles and the confining walls. In general, therefore, active fluids have no equation of state. Their mechanical pressure exhibits anomalous properties that defy the familiar thermodynamic reasoning that holds in equilibrium. The pressure remains a function of state, however, in some specific and well-studied active models that tacitly restrict the character of the particle-wall and/or particle-particle interactions.

  14. 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.

  15. 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. PMID:16825516

  16. 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.

  17. 20 CFR 641.864 - What functions and activities constitute programmatic activity costs?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... program, except that no amounts provided under the grant may be used to pay the cost of pension benefits... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false What functions and activities constitute programmatic activity costs? 641.864 Section 641.864 Employees' Benefits EMPLOYMENT AND TRAINING...

  18. 20 CFR 641.864 - What functions and activities constitute programmatic activity costs?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... program, except that no amounts provided under the grant may be used to pay the cost of pension benefits... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false What functions and activities constitute programmatic activity costs? 641.864 Section 641.864 Employees' Benefits EMPLOYMENT AND TRAINING...

  19. 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

  20. 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.

  1. Functions of AMP-activated protein kinase in adipose tissue

    PubMed Central

    Daval, Marie; Foufelle, Fabienne; Ferré, Pascal

    2006-01-01

    AMP-activated protein kinase (AMPK) is involved in cellular energy homeostasis. Its functions have been extensively studied in muscles and liver. AMPK stimulates pathways which increase energy production (glucose transport, fatty acid oxidation) and switches off pathways which consume energy (lipogenesis, protein synthesis, gluconeogenesis). This has led to the concept that AMPK has an interesting pharmaceutical potential in situations of insulin resistance and it is indeed the target of existing drugs and hormones which improve insulin sensitivity. Adipose tissue is a key player in energy metabolism through the release of substrates and hormones involved in metabolism and insulin sensitivity. Activation of AMPK in adipose tissue can be achieved through situations such as fasting and exercise. Leptin and adiponectin as well as hypoglycaemic drugs are activators of adipose tissue AMPK. This activation probably involves changes in the AMP/ATP ratio and the upstream kinase LKB1. When activated, AMPK limits fatty acid efflux from adipocytes and favours local fatty acid oxidation. Since fatty acids have a key role in insulin resistance, especially in muscles, activating AMPK in adipose tissue might be found to be beneficial in insulin-resistant states, particularly as AMPK activation also reduces cytokine secretion in adipocytes. PMID:16709632

  2. Toxoplasma gondii Actively Inhibits Neuronal Function in Chronically Infected Mice

    PubMed Central

    Haroon, Fahad; Händel, Ulrike; Angenstein, Frank; Goldschmidt, Jürgen; Kreutzmann, Peter; Lison, Holger; Fischer, Klaus-Dieter; Scheich, Henning; Wetzel, Wolfram; Schlüter, Dirk; Budinger, Eike

    2012-01-01

    Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii–infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca2+) imaging studies revealed that tachyzoites actively manipulated Ca2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host. PMID:22530040

  3. 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.

  4. Studies of higher nervous activity in functional phychoses.

    PubMed

    Astrup, C

    1975-01-01

    Psychiatric illnesses can be conceived of as experiments of nature, providing a variety of pathopsychological mechanisms which may elucidate normal psychological processes. Clinically the reactive psychoses are predominantly psychogenic reaction types. They present disturbances of higher nervous activity, similar to those of the neuroses. The unconditional reflex activity is practically as in normal controls, and the most outstanding finding was the large effect of psychodynamic complex structures. This is a physiological parallel to the clinical manifestations with great concern over experienced mental trauma. In the manic-depressive psychoses the most characteristic feature is a marked disturbance of unconditional reflex activity. This factor may be an important physiological mechanism underlying the more biological than psychodynamic reaction type and partly explain the changes of mood and associated interferences with sleep, body weight, sexual activity, aggression and other instinctual and vegetative functions. Schizophrenic psychoses also present changes of unconditional reflex activity, predominantly in the direction of inhibition of response. In addition there are severe dissociations within and between the three levels of unconditional reflexes and the two signaling systems. It is suggested that schizophrenia represents a functional maladaptation, which can be explained from the principles of autokinesis and schizokinesis established by Gantt in animal experiments. Prognostic models based on experimentally established impairment of performances were shown to predict long-term risks of schizophrenic defects just as well as models based on constellations of clinical symptoms. I would predict that psychophysiology and experimental psychology will become increasingly more important for establishing diagnosis and prognosis in the functional psychoses. The data of this article point toward a basis for a prophylactic psychiatry. PMID:1236657

  5. Jungle honey enhances immune function and antitumor activity.

    PubMed

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

    2011-01-01

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

  6. 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

  7. 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.

  8. Electrical activity patterns and the functional maturation of the neocortex.

    PubMed

    Kilb, Werner; Kirischuk, Sergei; Luhmann, Heiko J

    2011-11-01

    At the earliest developmental stages, sensory neocortical areas in various species reveal distinct patterns of spontaneous neuronal network activity. These activity patterns either propagate over large neocortical areas or synchronize local neuronal ensembles. In vitro and in vivo experiments indicate that these spontaneous activity patterns are generated from neuronal networks in the cerebral cortex, in subcortical structures or in the sensory periphery (retina, cochlea, whiskers). At early stages spontaneous periphery-driven and also sensory evoked activity is relayed to the developing cerebral cortex via the thalamus and the neocortical subplate, which amplifies the afferent sensory input. These early local and large-scale neuronal activity patterns influence a variety of developmental processes during corticogenesis, such as neurogenesis, apoptosis, neuronal migration, differentiation and network formation. The experimental data also indicate that disturbances in early neuronal patterns may have an impact on the development of cortical layers, columns and networks. In this article we review our current knowledge on the origin of early electrical activity patterns in neocortical sensory areas and their functional implications on shaping developing cortical networks.

  9. The Structure of A Biologically Active Estrogen Receptor-Coactivator Complex on DNA

    PubMed Central

    Yi, Ping; Wang, Zhao; Feng, Qin; Pintilie, Grigore D.; Foulds, Charles E.; Lanz, Rainer B.; Ludtke, Steven J.; Schmid, Michael F.; Chiu, Wah; O’Malley, Bert W.

    2015-01-01

    SUMMARY Estrogen receptor (ER) is a transcription factor critical for development, reproduction, metabolism and cancer. ER function hinges on its ability to recruit primary and secondary coactivators, yet structural information on the full-length receptor-coactivator complex to complement pre-existing and sometimes controversial biochemical information is lacking. Here we use cryo-EM to determine the quaternary structure of an active complex of DNA-bound ERα, steroid receptor coactivator 3 (SRC-3) and a secondary coactivator (p300). Our structural model suggests the following assembly mechanism for the complex: each of the two ligand-bound ERα monomers independently recruits one SRC-3 protein via the transactivation domain of ERα; the two SRC-3s in turn bind to different regions of one p300 protein through multiple contacts. We also present structural evidence for the location of activation function 1 (AF-1) in a full-length nuclear receptor, which supports a role for AF-1 in SRC-3 recruitment. PMID:25728767

  10. In vivo interaction of steroid receptor coactivator (SRC)-1 and the activation function-2 domain of the thyroid hormone receptor (TR) beta in TRbeta E457A knock-in and SRC-1 knockout mice.

    PubMed

    Alonso, Manuela; Goodwin, Charles; Liao, Xiaohui; Ortiga-Carvalho, Tania; Machado, Danielle S; Wondisford, Fredric E; Refetoff, Samuel; Weiss, Roy E

    2009-08-01

    The activation function-2 (AF-2) domain of the thyroid hormone (TH) receptor (TR)-beta is a TH-dependent binding site for nuclear coactivators (NCoA), which modulate TH-dependent gene transcription. In contrast, the putative AF-1 domain is a TH-independent region interacting with NCoA. We determined the specificity of the AF-2 domain and NCoA interaction by evaluating thyroid function in mice with combined disruption of the AF-2 domain in TRbeta, due to a point mutation (E457A), and deletion of one of the NCoAs, steroid receptor coactivator (SRC)-1. The E457A mutation was chosen because it abolishes NCoA recruitment in vitro while preserving normal TH binding and corepressor interactions resulting in resistance to TH. At baseline, disruption of SRC-1 in the homozygous knock-in (TRbeta(E457A/E457A)) mice worsened the degree of resistance to TH, resulting in increased serum T(4) and TSH. During TH deprivation, disruption of AF-2 and SRC-1 resulted in a TSH rise 50% of what was seen when AF-2 alone was removed, suggesting that SRC-1 was interacting outside of the AF-2 domain. Therefore, 1) during TH deprivation, SRC-1 is necessary for activating the hypothalamic-pituitary-thyroid axis; 2) ligand-dependent repression of TSH requires an intact AF-2; and 3) SRC-1 may interact with the another region of the TRbeta or the TRalpha to regulate TH action in the pituitary. This report demonstrates the dual interaction of NCoA in vivo: the TH-independent up-regulation possibly through another domain and TH-dependent down-regulation through the AF-2 domain. PMID:19406944

  11. Transfer Function between EEG and BOLD Signals of Epileptic Activity

    PubMed Central

    Leite, Marco; Leal, Alberto; Figueiredo, Patrícia

    2013-01-01

    Simultaneous electroencephalogram (EEG)-functional Magnetic Resonance Imaging (fMRI) recordings have seen growing application in the evaluation of epilepsy, namely in the characterization of brain networks related to epileptic activity. In EEG-correlated fMRI studies, epileptic events are usually described as boxcar signals based on the timing information retrieved from the EEG, and subsequently convolved with a hemodynamic response function to model the associated Blood Oxygen Level Dependent (BOLD) changes. Although more flexible approaches may allow a higher degree of complexity for the hemodynamics, the issue of how to model these dynamics based on the EEG remains an open question. In this work, a new methodology for the integration of simultaneous EEG-fMRI data in epilepsy is proposed, which incorporates a transfer function from the EEG to the BOLD signal. Independent component analysis of the EEG is performed, and a number of metrics expressing different models of the EEG-BOLD transfer function are extracted from the resulting time courses. These metrics are then used to predict the fMRI data and to identify brain areas associated with the EEG epileptic activity. The methodology was tested on both ictal and interictal EEG-fMRI recordings from one patient with a hypothalamic hamartoma. When compared to the conventional analysis approach, plausible, consistent, and more significant activations were obtained. Importantly, frequency-weighted EEG metrics yielded superior results than those weighted solely on the EEG power, which comes in agreement with previous literature. Reproducibility, specificity, and sensitivity should be addressed in an extended group of patients in order to further validate the proposed methodology and generalize the presented proof of concept. PMID:23355832

  12. Insilico studies of organosulfur-functional active compounds in garlic.

    PubMed

    Singh, Yogendra P; Singh, Ram A

    2010-01-01

    Garlic has been used medicinally since antiquity because of its antimicrobial activity, anticancer activity, antioxidant activity, ability to reduce cardiovascular diseases, improving immune functions, and antidiabetic activities and also in reducing cardiovascular diseases and improving immune functions. Recent studies identify that the wide variety of medicinal functions are attributed to the sulfur compounds present in garlic. Epidemiological observations and laboratory studies in animal models have also showed anticarcinogenic potential of organosulfur compounds of garlic. In this study, in silico analysis of organosulfur compounds is reported using the methods of theoretical chemistry to elucidate the molecular properties of garlic as it is more time and cost efficient, reduces the number of wet experiments, and offers the possibility of replacing some animal tests with suitable in silico models. The analysis of molecular descriptors defined by Lipinski has been done. The solubility of drug in water has been determined as it is of useful importance in the process of drug discovery from molecular design to pharmaceutical formulation and biopharmacy. All toxicities associated with candidate drug have been calculated. P-Glycoprotein expressed in normal tissues as a cause of drug pharmacokinetics and pharmacodynamics has been examined. Drug-plasma protein binding and volume of distribution have also been calculated. To avoid rejection of drugs, it is becoming more important to determine pK(a), absorption, polar surface area, and other physiochemical properties associated with a drug, before synthetic work is undertaken. The present in silico study is aimed at examining these compounds of garlic to evaluate its possible efficacy and toxicity under conditions of actual use in humans. PMID:20641079

  13. Aspartame degradation as a function of "water activity".

    PubMed

    Bell, L N; Labuza, T P

    1991-01-01

    The incorporation of aspartame into an increasing number of foods necessitates evaluation of its degradation kinetics as a function of "water activity" (aw). The kinetics of degradation were followed in model systems as a function of initial pH, temperature, and aw. An increase in aw, for each 0.1 units in the 0.3 to 0.7 range, resulted in about a 30-80% increase in degradation rate, which then decreased only slowly up to dilute solution. The presence of oil increased the degradation rate at high aw, but glucose had no effect on the rate of aspartame loss. The activation energies for loss ranged from 25 to 20 kcal/mole, decreasing as aw increased, as expected. The rates as a function of pH showed that the actual pH of the water in the condensed phase, based on the Bronsted relationship, may be very different than the initial pH. This caused a shift in the pH at which the fastest rate of degradation occurred, as aw increased.

  14. [The gaze and functional hemispheric activation in normal subjects].

    PubMed

    Gallois, P; Hautecoeur, P; Ovelacq, E; Gras, P; Dereux, J F

    1985-01-01

    The aim of this work was to determine whether the study of lateral and vertical conjugated eye movement could serve as an indicator of the functional hemispheric activation. Questions of vocabulary, calculation, logic (V.C.L.) and visuo-spatial instructions, as well as music-listening (V.S.M.), were proposed to 60 control subjects (21 men, 39 women). They were divided in 4 groups of 15 according to their laterality (complete right handed, incomplete right handed, ambidextrous, left handed). Eye movements were recorded using a video system. Deviations of the eyes towards the right and left, upwards and downwards, as well as episodes of staring were noted. Concerning V.C.L. questions, there was a significant correlation between conjugated lateral eye movements and the contralateral hemisphere activation. The study of vertical eye movements revealed a correlation only in complete right-handed and left-handed subjects: deviation upwards during the left hemisphere activation, and downwards during the right hemisphere activation. This pattern of response was no longer found during V.S.M. questions which, in the 4 groups, evoked staring episodes in 56 to 72 per cent of the cases. The negative emotional stimuli (emotional words, non verbal stimuli, stressful situations) evoked preferentially, but independently of laterality, deviations towards the left and downwards in favor of the right hemisphere activation. This method of observation of eye movements seems therefore of significant interest in Neuropsychology, provided that methodologic rules are rigorously respected.

  15. [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

  16. Biological function of activation-induced cytidine deaminase (AID).

    PubMed

    Kumar, Ritu; DiMenna, Lauren J; Chaudhuri, Jayanta; Evans, Todd

    2014-01-01

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

  17. Functional activity of mitochondria in cultured neural precursor cells.

    PubMed

    Plotnikov, E Yu; Marei, M V; Podgornyi, O V; Aleksandrova, M A; Zorov, D B; Sukhikh, G T

    2006-01-01

    We studied mitochondrial transmembrane potential of neural precursor cells forming neurospheres in culture. Uneven energization of mitochondria in neurosphere cells was detected. Heterogeneity of cells by the mitochondrial potential increased with neurosphere enlargement during culturing. Decrease in the mitochondrial potential in the central cells in large spheres, presumably caused by insufficient diffusion of oxygen and nutrients, can provoke their damage and death. Population of cells with high mitochondrial potential responded to addition of the nuclear dye by a decrease in mitochondrial potential, which can indicate functioning of ABCG2 complex in these cells, characteristic of undifferentiated stem cells. These data will help to create optimum conditions for culturing of neural stem cells for the maintenance of their maximum functional and proliferative activity. PMID:16929986

  18. 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.

  19. 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

  20. 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.

  1. Hemodynamic responses to functional activation accessed by optical imaging

    NASA Astrophysics Data System (ADS)

    Ni, Songlin; Li, Pengcheng; Yang, Yuanyuan; Lv, Xiaohua; Luo, Qingming

    2006-01-01

    A multi-wavelength light-emitting diode (LED) and laser diode (LD) based optical imaging system was developed to visualize the changes in cerebral blood flow, oxygenation following functional activation simultaneously in rodent cortex. The 2-D blood flow image was accessed by laser speckle contrast imaging, and the spectroscopic imaging of intrinsic signal was used for the calculation of oxyhemoglobin (HbO), deoxyhemoglobin (Hb) and total hemoglobin (HbT) concentration. The combination of spectroscopic imaging and laser speckle contrast imaging provides the capability to simultaneously investigate the spatial and temporal blood flow and hemoglobin concentration changes with high resolution, which may lead to a better understanding of the coupling between neuronal activation and vascular responses. The optical imaging system been built is compact and convenient to investigators. And it is reliable to acquire raw data. In present study, the hemodynamic responses to cortical spreading depression (CSD) in parietal cortex of ~-chloralose/urethan anesthetized rats were demonstrated.

  2. Diesel-Enriched Particulate Matter Functionally Activates Human Dendritic Cells

    PubMed Central

    Porter, Michael; Karp, Matthew; Killedar, Smruti; Bauer, Stephen M.; Guo, Jia; Williams, D'Ann; Breysse, Patrick; Georas, Steve N.; Williams, Marc A.

    2007-01-01

    Epidemiologic studies have associated exposure to airborne particulate matter (PM) with exacerbations of asthma. It is unknown how different sources of PM affect innate immunity. We sought to determine how car- and diesel exhaust–derived PM affects dendritic cell (DC) activation. DC development was modeled using CD34+ hematopoietic progenitors. Airborne PM was collected from exhaust plenums of Fort McHenry Tunnel providing car-enriched particles (CEP) and diesel-enriched particles (DEP). DC were stimulated for 48 hours with CEP, DEP, CD40-ligand, or lipopolysaccharide. DC activation was assessed by flow cytometry, enzyme-linked immunosorbent assay, and standard culture techniques. DEP increased uptake of fluorescein isothiocyanate–dextran (a model antigen) by DC. Diesel particles enhanced cell-surface expression of co-stimulatory molecules (e.g., CD40 [P < 0.01] and MHC class II [P < 0.01]). By contrast, CEP poorly affected antigen uptake and expression of cell surface molecules, and did not greatly affect cytokine secretion by DC. However, DEP increased production of TNF, IL-6, and IFN-γ (P < 0.01), IL-12 (P < 0.05), and vascular endothelial growth factor (P < 0.001). In co-stimulation assays of PM-exposed DC and alloreactive CD4+ T cells, both CEP and DEP directed a Th2-like pattern of cytokine production (e.g., enhanced IL-13 and IL-18 and suppressed IFN-γ production). CD4+ T cells were not functionally activated on exposure to either DEP or CEP. Car- and diesel-enriched particles exert a differential effect on DC activation. Our data support the hypothesis that DEP (and to a lesser extent CEP) regulate important functional aspects of human DC, supporting an adjuvant role for this material. PMID:17630318

  3. 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.

  4. Dual Function of Phosphoubiquitin in E3 Activation of Parkin.

    PubMed

    Walinda, Erik; Morimoto, Daichi; Sugase, Kenji; Shirakawa, Masahiro

    2016-08-01

    Mutations in the gene encoding parkin, an auto-inhibited E3 ubiquitin ligase that functions in the clearance of damaged mitochondria, are the most common cause of autosomal recessive juvenile Parkinsonism. The mechanism regulating parkin activation remains poorly understood. Here we show, by using isothermal titration calorimetry, solution NMR, and fluorescence spectroscopy, that parkin can bind ubiquitin and phosphomimetic ubiquitin by recognizing the canonical hydrophobic patch and C terminus of ubiquitin. The affinity of parkin for both phosphomimetic and unmodified ubiquitin is markedly enhanced upon removal of the ubiquitin-like (UBL) domain of parkin. This suggests that the agonistic binding of ubiquitin to parkin in trans is counterbalanced by the antagonistic activity of the parkin UBL domain in cis Intriguingly, UBL binding is enthalpy-driven, whereas ubiquitin binding is driven by an increase in the total entropy of the system. These thermodynamic differences are explained by different chemistry in the ubiquitin- and UBL-binding pockets of parkin and, as shown by molecular dynamics simulations, are not a consequence of changes in protein conformational entropy. Indeed, comparison of conformational fluctuations reveals that the RING1-IBR element becomes considerably more rigid upon complex formation. A model of parkin activation is proposed in which E2∼Ub binding triggers large scale diffusional motion of the RING2 domain toward the ubiquitin-stabilized RING1-IBR assembly to complete formation of the active parkin-E2∼Ub transfer complex. Thus, ubiquitin plays a dual role in parkin activation by competing with the inhibitory UBL domain and stabilizing the active form of parkin. PMID:27284007

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

    PubMed

    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

  6. Activities and Programs That Improve Children's Executive Functions.

    PubMed

    Diamond, Adele

    2012-10-01

    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

  7. 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

  8. Antihelminthic niclosamide modulates dendritic cells activation and function.

    PubMed

    Wu, Chieh-Shan; Li, Yi-Rong; Chen, Jeremy J W; Chen, Ying-Che; Chu, Chiang-Liang; Pan, I-Hong; Wu, Yu-Shan; Lin, Chi-Chen

    2014-01-01

    Dendritic cells (DCs) link the sensing of the environment by the innate immune system to the initiation of adaptive immune responses. Accordingly, DCs are considered to be a major target in the development of immunomodulating compounds. In this study, the effect of niclosamide, a Food and Drug Administration-approved antihelminthic drug, on the activation of lipopolysaccharide (LPS)-stimulated murine bone marrow-derived DCs was examined. Our experimental results show that niclosamide reduced the pro-inflammatory cytokine and chemokine expression of LPS-activated DCs. In addition, niclosamide also affected the expression of MHC and costimulatory molecules and influenced the ability of the cells to take up antigens. Therefore, in mixed cell cultures composed of syngeneic OVA-specific T cells and DCs, niclosamide-treated DCs showed a decreased ability to stimulate T cell proliferation and IFN-γ production. Furthermore, intravenous injection of niclosamide also attenuated contact hypersensitivity (CHS) in mice during sensitization with 2,4-dinitro-1-fluorobenzene. Blocking the LPS-induced activation of MAPK-ERK, JNK and NF-κB may contribute to the inhibitory effect of niclosamide on DC activation. Collectively, our findings suggest that niclosamide can manipulate the function of DCs. These results provide new insight into the immunopharmacological role of niclosamide and suggest that it may be useful for the treatment of chronic inflammatory disorders or DC-mediated autoimmune diseases. PMID:24561310

  9. Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

    PubMed Central

    Chen, Der-Yuan; Song, Pei-Shan; Hong, Jau-Shyong; Chu, Ching-Liang; Pan, I-Horng; Chen, Yi-Ming; Lin, Ching-Hsiung; Lin, Sheng-Hao; Lin, Chi-Chen

    2013-01-01

    Dendritic cells (DCs) play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM), a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs) was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS), proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-κB translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs). These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases. PMID:23781253

  10. Activities and Programs That Improve Children's Executive Functions.

    PubMed

    Diamond, Adele

    2012-10-01

    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.

  11. Dextromethorphan inhibits activations and functions in dendritic cells.

    PubMed

    Chen, Der-Yuan; Song, Pei-Shan; Hong, Jau-Shyong; Chu, Ching-Liang; Pan, I-Horng; Chen, Yi-Ming; Lin, Ching-Hsiung; Lin, Sheng-Hao; Lin, Chi-Chen

    2013-01-01

    Dendritic cells (DCs) play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM), a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs) was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS), proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN- γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF- κ B translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs). These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases. PMID:23781253

  12. Predicting activity approach based on new atoms similarity kernel function.

    PubMed

    Abu El-Atta, Ahmed H; Moussa, M I; Hassanien, Aboul Ella

    2015-07-01

    Drug design is a high cost and long term process. To reduce time and costs for drugs discoveries, new techniques are needed. Chemoinformatics field implements the informational techniques and computer science like machine learning and graph theory to discover the chemical compounds properties, such as toxicity or biological activity. This is done through analyzing their molecular structure (molecular graph). To overcome this problem there is an increasing need for algorithms to analyze and classify graph data to predict the activity of molecules. Kernels methods provide a powerful framework which combines machine learning with graph theory techniques. These kernels methods have led to impressive performance results in many several chemoinformatics problems like biological activity prediction. This paper presents a new approach based on kernel functions to solve activity prediction problem for chemical compounds. First we encode all atoms depending on their neighbors then we use these codes to find a relationship between those atoms each other. Then we use relation between different atoms to find similarity between chemical compounds. The proposed approach was compared with many other classification methods and the results show competitive accuracy with these methods.

  13. 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

  14. 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.

  15. Structural aspects of calcium-release activated calcium channel function

    PubMed Central

    Stathopulos, Peter B; Ikura, Mitsuhiko

    2013-01-01

    Store-operated calcium (Ca2+) entry is the process by which molecules located on the endo/sarcoplasmic reticulum (ER/SR) respond to decreased luminal Ca2+ levels by signaling Ca2+ release activated Ca2+ channels (CRAC) channels to open on the plasma membrane (PM). This activation of PM CRAC channels provides a sustained cytosolic Ca2+ elevation associated with myriad physiological processes. The identities of the molecules which mediate SOCE include stromal interaction molecules (STIMs), functioning as the ER/SR luminal Ca2+ sensors, and Orai proteins, forming the PM CRAC channels. This review examines the current available high-resolution structural information on these CRAC molecular components with particular focus on the solution structures of the luminal STIM Ca2+ sensing domains, the crystal structures of cytosolic STIM fragments, a closed Orai hexameric crystal structure and a structure of an Orai1 N-terminal fragment in complex with calmodulin. The accessible structural data are discussed in terms of potential mechanisms of action and cohesiveness with functional observations. PMID:24213636

  16. 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.

  17. 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. PMID:27243042

  18. Structure activity relationships: their function in biological prediction

    SciTech Connect

    Schultz, T.W.

    1982-01-01

    Quantitative structure activity relationships provide a means of ranking or predicting biological effects based on chemical structure. For each compound used to formulate a structure activity model two kinds of quantitative information are required: (1) biological activity and (2) molecular properties. Molecular properties are of three types: (1) molecular shape, (2) physiochemical parameters, and (3) abstract quantitations of molecular structure. Currently the two best descriptors are the hydrophobic parameter, log 1-octanol/water partition coefficient (log P), and the /sup 1/X/sup v/(one-chi-v) molecular connectivity index. Biological responses can be divided into three main categories: (1) non-specific effects due to membrane perturbation, (2) non-specific effects due to interaction with functional groups of proteins, and (3) specific effects due to interaction with receptors. Twenty-six synthetic fossil fuel-related nitrogen-containing aromatic compounds were examined to determine the quantitative correlation between log P and /sup 1/X/sup v/ and population growth impairment of Tetrahymena pyriformis. Nitro-containing compounds are the most active, followed by amino-containing compounds and azaarenes. Within each analog series activity increases with alkyl substitution and ring addition. The planar model log BR = 0.5564 log P + 0.3000 /sup 1/X/sup v/ -2.0138 was determined using mono-nitrogen substituted compounds. Attempts to extrapolate this model to dinitrogen-containing molecules were, for the most part, unsuccessful because of a change in mode of action from membrane perturbation to uncoupling of oxidative phosphoralation.

  19. Estimation of spatiotemporal neural activity using radial basis function networks.

    PubMed

    Anderson, R W; Das, S; Keller, E L

    1998-12-01

    We report a method using radial basis function (RBF) networks to estimate the time evolution of population activity in topologically organized neural structures from single-neuron recordings. This is an important problem in neuroscience research, as such estimates may provide insights into systems-level function of these structures. Since single-unit neural data tends to be unevenly sampled and highly variable under similar behavioral conditions, obtaining such estimates is a difficult task. In particular, a class of cells in the superior colliculus called buildup neurons can have very narrow regions of saccade vectors for which they discharge at high rates but very large surround regions over which they discharge at low, but not zero, levels. Estimating the dynamic movement fields for these cells for two spatial dimensions at closely spaced timed intervals is a difficult problem, and no general method has been described that can be applied to all buildup cells. Estimation of individual collicular cells' spatiotemporal movement fields is a prerequisite for obtaining reliable two-dimensional estimates of the population activity on the collicular motor map during saccades. Therefore, we have developed several computational-geometry-based algorithms that regularize the data before computing a surface estimation using RBF networks. The method is then expanded to the problem of estimating simultaneous spatiotemporal activity occurring across the superior colliculus during a single movement (the inverse problem). In principle, this methodology could be applied to any neural structure with a regular, two-dimensional organization, provided a sufficient spatial distribution of sampled neurons is available.

  20. 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.

  1. Functional consequences of caspase activation in cardiac myocytes

    NASA Astrophysics Data System (ADS)

    Communal, Catherine; Sumandea, Marius; de Tombe, Pieter; Narula, Jagat; Solaro, R. John; Hajjar, Roger J.

    2002-04-01

    Cardiomyocyte apoptosis is present in many cardiac disease states, including heart failure and ischemic heart disease. Apoptosis is associated with the activation of caspases that mediate the cleavage of vital and structural proteins. However, the functional contribution of apoptosis to these conditions is not known. Furthermore, in cardiac myocytes, apoptosis may not be complete, allowing the cells to persist for a prolonged period within the myocardium. Therefore, we examined whether caspase-3 cleaved cardiac myofibrillar proteins and, if so, whether it affects contractile function. The effects of caspase-3 were studied in vitro on individual components of the cardiac myofilament including -actin, -actinin, myosin heavy chain, myosin light chain 1/2, tropomyosin, cardiac troponins (T, I, C), and the trimeric troponin complex. Exposure of the myofibrillar protein (listed above) to caspase-3 for 4 h resulted in the cleavage of -actin and -actinin, but not myosin heavy chain, myosin light chain 1/2, and tropomyosin, into three fragments (30, 20, and 15 kDa) and one major fragment (45 kDa), respectively. When cTnT, cTnI, and cTnC were incubated individually with caspase-3, there was no detectable cleavage. However, when the recombinant troponin complex was exposed to caspase-3, cTnT was cleaved, resulting in fragments of 25 kDa. Furthermore, rat cardiac myofilaments exposed to caspase-3 exhibited similar patterns of myofibrillar protein cleavage. Treatment with the caspase inhibitor DEVD-CHO or z-VAD-fmk abolished the cleavage. Myofilaments, isolated from adult rat ventricular myocytes after induction of apoptotic pathway by using -adrenergic stimulation, displayed a similar pattern of actin and TnT cleavage. Exposure of skinned fiber to caspase-3 decreased maximal Ca2+-activated force and myofibrillar ATPase activity. Our results indicate that caspase-3 cleaved myofibrillar proteins, resulting in an impaired force/Ca2+ relationship and myofibrillar ATPase activity

  2. Functional role of lipid rafts in CD20 activity?

    PubMed

    Janas, Eva; Priest, Richard; Malhotra, Rajneesh

    2005-01-01

    CD20 is a B-lymphocyte-specific integral membrane protein, implicated in the regulation of transmembrane calcium conductance, cell-cycle progression and B-lymphocyte proliferation. CD20 is proposed to function as a SOCC (store-operated calcium channel). SOCCs are activated by receptor-stimulated calcium depletion of intracellular stores. Sustained calcium conductivity across the plasma membrane mediated by SOCC activity is required for long-term calcium-dependent processes, such as transcriptional control and gene expression. Cross-linking of CD20 by antibodies (e.g. Rituxan) has been reported to induce a rapid redistribution of CD20 into specialized microdomains at the plasma membrane, known as lipid rafts. Recruitment of CD20 into lipid rafts and its homo-oligomerization are suggested to be crucial for CD20 activity and regulation. This review outlines recent biochemical studies characterizing the role of CD20 in calcium signalling in B-lymphocytes and evaluates an engagement of lipid rafts in the regulation of CD20-mediated calcium conductivity.

  3. 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. PMID:16436103

  4. What are antibiotics? Archaic functions for modern activities.

    PubMed

    Davies, J

    1990-08-01

    Secondary metabolites are proposed to have played important roles in the evolution of the reactions of living forms on earth, in effecting and modulating reactions during biochemical evolution by chemical and structural interaction with 'receptor' sites in primitive macromolecular templates. For example, in the evolution of the translation system, as the polymerizing reactions became more complex and proteins became involved, the low molecular-weight effectors were functionally replaced by polypeptides, but retained their ability to interact with receptor sites in nucleic acids and proteins. Many of these low molecular-weight effectors now play a different role, that of antagonists, by interacting with the original receptor sites in macromolecular structures; this explains their contemporary activity as antibiotics.

  5. Bipartite functions of the CREB co-activators selectively direct alternative splicing or transcriptional activation.

    PubMed

    Amelio, Antonio L; Caputi, Massimo; Conkright, Michael D

    2009-09-16

    The CREB regulated transcription co-activators (CRTCs) regulate many biological processes by integrating and converting environmental inputs into transcriptional responses. Although the mechanisms by which CRTCs sense cellular signals are characterized, little is known regarding how CRTCs contribute to the regulation of cAMP inducible genes. Here we show that these dynamic regulators, unlike other co-activators, independently direct either pre-mRNA splice-site selection or transcriptional activation depending on the cell type or promoter context. Moreover, in other scenarios, the CRTC co-activators coordinately regulate transcription and splicing. Mutational analyses showed that CRTCs possess distinct functional domains responsible for regulating either pre-mRNA splicing or transcriptional activation. Interestingly, the CRTC1-MAML2 oncoprotein lacks the splicing domain and is incapable of altering splice-site selection despite robustly activating transcription. The differential usage of these distinct domains allows CRTCs to selectively mediate multiple facets of gene regulation, indicating that co-activators are not solely restricted to coordinating alternative splicing with increase in transcriptional activity.

  6. Sympathetic activation and nitric oxide function in early hypertension

    PubMed Central

    Okamoto, Luis E.; Diedrich, André; Choi, Leena; Robertson, David; Farley, Ginnie; Paranjape, Sachin; Biaggioni, Italo

    2012-01-01

    The purpose of this study was to determine if tonic restrain of blood pressure by nitric oxide (NO) is impaired early in the development of hypertension. Impaired NO function is thought to contribute to hypertension, but it is not clear if this is explained by direct effects of NO on vascular tone or indirect modulation of sympathetic activity. We determined the blood pressure effect of NO synthase inhibition with Nω-monomethyl-l-arginine (l-NMMA) during autonomic blockade with trimethaphan to eliminate baroreflex buffering and NO modulation of autonomic tone. In this setting, impaired NO modulation of vascular tone would be reflected as a blunted pressor response to l-NMMA. We enrolled a total of 66 subjects (39 ± 1.3 yr old, 30 females), 20 normotensives, 20 prehypertensives (blood pressure between 120/80 and 140/90 mmHg), 17 hypertensives, and 9 smokers (included as “positive” controls of impaired NO function). Trimethaphan normalized blood pressure in hypertensives, suggesting increased sympathetic tone contributing to hypertension. In contrast, l-NMMA produced similar increases in systolic blood pressure in normal, prehypertensive, and hypertensive subjects (31 ± 2, 32 ± 2, and 30 ± 3 mmHg, respectively), whereas the response of smokers was blunted (16 ± 5 mmHg, P = 0.012). Our results suggest that sympathetic activity plays a role in hypertension. NO tonically restrains blood pressure by ∼30 mmHg, but we found no evidence of impaired modulation by NO of vascular tone contributing to the early development of hypertension. If NO deficiency contributes to hypertension, it is likely to be through its modulation of the autonomic nervous system, which was excluded in this study. PMID:22287587

  7. Functional, biophysical, and structural bases for antibacterial activity of tigecycline.

    PubMed

    Olson, Matthew W; Ruzin, Alexey; Feyfant, Eric; Rush, Thomas S; O'Connell, John; Bradford, Patricia A

    2006-06-01

    Tigecycline is a novel glycylcycline antibiotic that possesses broad-spectrum activity against many clinically relevant species of bacterial pathogens. The mechanism of action of tigecycline was delineated using functional, biophysical, and molecular modeling experiments in this study. Functional assays showed that tigecycline specifically inhibits bacterial protein synthesis with potency 3- and 20-fold greater than that of minocycline and tetracycline, respectively. Biophysical analyses demonstrated that isolated ribosomes bind tigecycline, minocycline, and tetracycline with dissociation constant values of 10(-8), 10(-7), and >10(-6) M, respectively. A molecular model of tigecycline bound to the ribosome was generated with the aid of a 3.40-angstrom resolution X-ray diffraction structure of the 30S ribosomal subunit from Thermus thermophilus. This model places tigecycline in the A site of the 30S subunit and involves substantial interactions with residues of H34 of the ribosomal subunit. These interactions were not observed in a model of tetracycline binding. Modeling data were consistent with the biochemical and biophysical data generated in this and other recent studies and suggested that tigecycline binds to bacterial ribosomes in a novel way that allows it to overcome tetracycline resistance due to ribosomal protection.

  8. Active plasma resonance spectroscopy: a functional analytic description

    NASA Astrophysics Data System (ADS)

    Lapke, M.; Oberrath, J.; Mussenbrock, T.; Brinkmann, R. P.

    2013-04-01

    The term ‘active plasma resonance spectroscopy’ denotes a class of diagnostic methods which employ the ability of plasmas to resonate on or near the plasma frequency. The basic idea dates back to the early days of discharge physics: a signal in the GHz range is coupled to the plasma via an electrical probe; the spectral response is recorded, and then evaluated with a mathematical model to obtain information on the electron density and other plasma parameters. In recent years, the concept has found renewed interest as a basis of industry compatible plasma diagnostics. This paper analyzes the diagnostic technique in terms of a general description based on functional analytic (or Hilbert Space) methods which hold for arbitrary probe geometries. It is shown that the response function of the plasma-probe system can be expressed as a matrix element of the resolvent of an appropriately defined dynamical operator. A specialization of the formalism to a symmetric probe design is given, as well as an interpretation in terms of a lumped circuit model consisting of series resonance circuits. We present ideas for an optimized probe design based on geometric and electrical symmetry.

  9. Sexual Function, Activity, and Satisfaction among Women Receiving Maintenance Hemodialysis

    PubMed Central

    Mor, Maria K.; Sevick, Mary Ann; Shields, Anne Marie; Green, Jamie A.; Palevsky, Paul M.; Arnold, Robert M.; Fine, Michael J.

    2014-01-01

    Summary Background and objectives Past studies that demonstrated that sexual dysfunction is common among women receiving chronic hemodialysis did not distinguish sexual dysfunction/difficulty from sexual inactivity. This study sought to differentiate these in order to elucidate the prevalence of true “sexual dysfunction” in this population. Design, setting, participants, & measurements As part of a clinical trial of symptom management strategies in patients receiving chronic hemodialysis, female sexual function was prospectively assessed monthly for 6 months and quarterly thereafter using the Female Sexual Function Index, to which questions were added differentiating sexual dysfunction/difficulty from sexual inactivity. Beginning in month 7, patients were asked three questions about sexual activity, difficulty, and satisfaction monthly. Results Of the women enrolled in the clinical trial,125 participants completed 1721 assessments between 2009 and 2011. Scores on 574 of 643 (89%) quarterly Female Sexual Function Index assessments were consistent with sexual dysfunction, due largely to sexual inactivity, which was reported on 525 (82%) quarterly assessments. When reported (n=1663), the most frequently described reasons for sexual inactivity were lack of interest in sex (n=715; 43%) and lack of a partner (n=647; 39%), but rarely sexual difficulty (n=36; 2%). When reported (n=1582), women were moderately to very satisfied with their sexual life on 1020 (64%) assessments and on 513 of 671 (76%) assessments in which lack of interest was cited as a reason for sexual inactivity. Women indicated an interest in learning about the causes of and treatment for sexual dysfunction on just 5% of all assessments. Conclusions Although many women receiving chronic hemodialysis are sexually inactive, few describe sexual difficulty. Most, including those with a lack of interest in sex, are satisfied with their sexual life and few wish to learn about treatment options. These

  10. Estimation of Evapotranspiration as a function of Photosynthetic Active Radiation

    NASA Astrophysics Data System (ADS)

    Wesley, E.; Migliaccio, K.; Judge, J.

    2012-12-01

    The purpose of this research project is to more accurately measure the water balance and energy movements to properly allocate water resources at the Snapper Creek Site in Miami-Dade County, FL, by quantifying and estimating evapotranspiration (ET). ET is generally estimated using weather based equations, this project focused on estimating ET as a function of Photosynthetic Active Radiation (PAR). The project objectives were first to compose a function of PAR and calculated coefficients that can accurately estimate daily ET values with the least amount of variables used in its estimation equation, and second, to compare the newly identified ET estimation PAR function to TURC estimations, in comparison to our actual Eddy Covariance (EC) ET data and determine the differences in ET values. PAR, volumetric water content (VWC), and temperature (T) data were quality checked and used in developing singular and multiple variable regression models fit with SigmaPlot software. Fifteen different ET estimation equations were evaluated against EC ET and TURC estimated ET using R2 and slope factors. The selected equation that best estimated EC ET was cross validated using a 5 month data set; its daily and monthly ET values and sums were compared against the commonly used TURC equation. Using a multiple variable regression model, an equation with three variables (i.e., VWC, T, and PAR) was identified that best fit EC ET daily data. However, a regression was also found that used only PAR and provided ET predictions of similar accuracy. The PAR based regression model predicted daily EC ET more accurately than the traditional TURC method. Using only PAR to estimate ET reduces the input variables as compared to using the TURC model which requires T and solar radiation. Thus, not only is the PAR approach more accurate but also more cost effective. The PAR-based ET estimation equation derived in this study may be over fit considering only 5 months of data were used to produce the PAR

  11. Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function.

    PubMed

    Parker, Lindsay M; Damanhuri, Hanafi A; Fletcher, Sophie P S; Goodchild, Ann K

    2015-04-16

    Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate.

  12. Mastering tricyclic ring systems for desirable functional cannabinoid activity

    PubMed Central

    Petrov, Ravil R.; Knight, Lindsay; Chen, Shao-Rui; Wager-Miller, Jim; McDaniel, Steven W.; Diaz, Fanny; Barth, Francis; Pan, Hui-Lin; Mackie, Ken; Cavasotto, Claudio N.; Diaz, Philippe

    2013-01-01

    There is growing interest in using cannabinoid receptor 2 (CB2) agonists for the treatment of neuropathic pain and other indications. In continuation of our ongoing program aiming for the development of new small molecule cannabinoid ligands, we have synthesized a novel series of carbazole and γ-carboline derivatives. The affinities of the newly synthesized compounds were determined by a competitive radioligand displacement assay for human CB2 cannabinoid receptor and rat CB1 cannabinoid receptor. Functional activity and selectivity at human CB1 and CB2 receptors were characterized using receptor internalization and [35S]GTP-γ-S assays. The structure-activity relationship and optimization studies of the carbazole series have led to the discovery of a non-selective CB1 and CB2 agonist, compound 4. Our subsequent research efforts to increase CB2 selectivity of this lead compound have led to the discovery of CB2 selective compound 64, which robustly internalized CB2 receptors. Compound 64 had potent inhibitory effects on pain hypersensitivity in a rat model of neuropathic pain. Other potent and CB2 receptor–selective compounds, including compounds 63 and 68, and a selective CB1 agonist, compound 74 were also discovered. In addition, we identified the CB2 ligand 35 which failed to promote CB2 receptor internalization and inhibited compound CP55,940-induced CB2 internalization despite a high CB2 receptor affinity. The present study provides novel tricyclic series as a starting point for further investigations of CB2 pharmacology and pain treatment. PMID:24125850

  13. 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. PMID:25288763

  14. 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

  15. Functional characterization of alpha-synuclein protein with antimicrobial activity.

    PubMed

    Park, Seong-Cheol; Moon, Jeong Chan; Shin, Su Young; Son, Hyosuk; Jung, Young Jun; Kim, Nam-Hong; Kim, Young-Min; Jang, Mi-Kyeong; Lee, Jung Ro

    2016-09-16

    Alpha-synuclein (α-Syn), a small (14 kDa) protein associated with Parkinson's disease, is abundant in human neural tissues. α-Syn plays an important role in maintaining a supply of synaptic vesicles in presynaptic terminals; however, the mechanism by which it performs this function are not well understood. In addition, there is a correlation between α-Syn over-expression and upregulation of an innate immune response. Given the growing body of literature surrounding antimicrobial peptides (AMPs) in the brain, and the similarities between α-Syn and a previously characterized AMP, Amyloid-β, we set out to investigate if α-Syn shares AMP-like properties. Here we demonstrate that α-Syn exhibits antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, we demonstrate a role for α-Syn in inhibiting various pathogenic fungal strains such as Aspergillus flavus, Aspergillus fumigatus and Rhizoctonia solani. We also analyzed localizations of recombinant α-Syn protein in E. coli and Candida albicans. These results suggest that in addition to α-Syn's role in neurotransmitter release, it appears to be a natural AMP. PMID:27520375

  16. Fluorescence-activated sorting of rat hepatocytes based on their mixed function oxidase activities towards diethoxyfluorescein.

    PubMed Central

    White, I N; Green, M L; Legg, R F

    1987-01-01

    The formation of ethoxyfluorescein and fluorescein from diethoxyfluorescein by isolated rat hepatocytes has been used as a basis for separating such cells dependent on their mixed function oxidase activities by fluorescence-activated flow cytometry. Five equal fractions defined by computer-generated regions were isolated. Non-viable cells with low fluorescence (region 1) represented 10-15% of the population, while the remainder with higher mixed function oxidase activities (regions 2-5), were greater than 95% viable by Trypan Blue exclusion. In region 1, 30% of the viable cells were binucleate, 67% diploid while in region 5, 13% were binucleate and 69% tetraploid. At 3 h after sorting, following attachment to glass coverslips, exposure of cells to methyl methanesulphonate, retrorsine or norethindrone resulted in unscheduled DNA synthesis which was 2-fold higher in the tetraploid-rich region 5, while aflatoxin B1, benzo[a]pyrene or 2-acetylaminofluorene caused a 5-fold increase in unscheduled DNA synthesis in these cells, relative to the diploid-rich hepatocytes in region 2. Images Fig. 4. PMID:3689348

  17. AMP-ACTIVATED PROTEIN KINASE ACTIVATION AS A STRATEGY FOR PROTECTING VASCULAR ENDOTHELIAL FUNCTION

    PubMed Central

    Zou, Ming-Hui; Wu, Yong

    2010-01-01

    SUMMARY 1. AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase involved in the regulation of cellular and organismal metabolism. AMPK has a heterotrimeric structure, consisting of a catalytic α-subunit and regulatory β- and γ-subunits, each of which has two or more isoforms that are differentially expressed in various tissues and that arise from distinct genes. The AMPK system acts as a sensor of cellular energy status that is conserved in all eukaryotic cells. In addition, AMPK is activated by physiological stimuli and oxidants. 2. The importance of AMPK in cardiovascular functions is best demonstrated by recent studies showing that widely used drugs, including statins, metformin and rosiglitazone, execute cardiovascular protective effects at least partly through the activation of AMPK. As a consequence, AMPK has been proposed as a candidate target for therapeutic intervention in the treatment of both Type 2 diabetes and metabolic syndrome owing to its central role in the regulation of energy balance; it may also have a role in weight control. 3. In the present brief review, we summarize the recent progress of AMPK signalling and regulation focusing on vascular endothelial cells. We further hypothesize that AMPK is a dual sensor for energy and redox status within a cell and AMPK may be a therapeutic target for protecting vascular endothelial function. PMID:18177481

  18. Altered Hub Functioning and Compensatory Activations in the Connectome: A Meta-Analysis of Functional Neuroimaging Studies in Schizophrenia

    PubMed Central

    Crossley, Nicolas A.; Mechelli, Andrea; Ginestet, Cedric; Rubinov, Mikail; Bullmore, Edward T.; McGuire, Philip

    2016-01-01

    Background: Functional neuroimaging studies of schizophrenia have identified abnormal activations in many brain regions. In an effort to interpret these findings from a network perspective, we carried out a meta-analysis of this literature, mapping anatomical locations of under- and over-activation to the topology of a normative human functional connectome. Methods: We included 314 task-based functional neuroimaging studies including more than 5000 patients with schizophrenia and over 5000 controls. Coordinates of significant under- or over-activations in patients relative to controls were mapped to nodes of a normative connectome defined by a prior meta-analysis of 1641 functional neuroimaging studies of task-related activation in healthy volunteers. Results: Under-activations and over-activations were reported in a wide diversity of brain regions. Both under- and over-activations were significantly more likely to be located in hub nodes that constitute the “rich club” or core of the normative connectome. In a subset of 121 studies that reported both under- and over-activations in the same patients, we found that, in network terms, these abnormalities were located in close topological proximity to each other. Under-activation in a peripheral node was more frequently associated specifically with over-activation of core nodes than with over-activation of another peripheral node. Conclusions: Although schizophrenia is associated with altered brain functional activation in a wide variety of regions, abnormal responses are concentrated in hubs of the normative connectome. Task-specific under-activation in schizophrenia is accompanied by over-activation of topologically central, less functionally specialized network nodes, which may represent a compensatory response. PMID:26472684

  19. High-throughput functional comparison of promoter and enhancer activities.

    PubMed

    Nguyen, Thomas A; Jones, Richard D; Snavely, Andrew R; Pfenning, Andreas R; Kirchner, Rory; Hemberg, Martin; Gray, Jesse M

    2016-08-01

    Promoters initiate RNA synthesis, and enhancers stimulate promoter activity. Whether promoter and enhancer activities are encoded distinctly in DNA sequences is unknown. We measured the enhancer and promoter activities of thousands of DNA fragments transduced into mouse neurons. We focused on genomic loci bound by the neuronal activity-regulated coactivator CREBBP, and we measured enhancer and promoter activities both before and after neuronal activation. We find that the same sequences typically encode both enhancer and promoter activities. However, gene promoters generate more promoter activity than distal enhancers, despite generating similar enhancer activity. Surprisingly, the greater promoter activity of gene promoters is not due to conventional core promoter elements or splicing signals. Instead, we find that particular transcription factor binding motifs are intrinsically biased toward the generation of promoter activity, whereas others are not. Although the specific biases we observe may be dependent on experimental or cellular context, our results suggest that gene promoters are distinguished from distal enhancers by specific complements of transcriptional activators. PMID:27311442

  20. 20 CFR 667.220 - What Workforce Investment Act title I functions and activities constitute the costs of...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... cash management functions; (ii) Procurement and purchasing functions; (iii) Property management functions; (iv) Personnel management functions; (v) Payroll functions; (vi) Coordinating the resolution of... functions and activities constitute the costs of administration subject to the administrative cost...

  1. The Contribution of Executive Functions to Participation in School Activities of Children with High Functioning Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Zingerevich, Chaya; Patricia D., LaVesser

    2009-01-01

    This study describes the contribution of executive functions to participation in school activities of children diagnosed with ASD ages 6-9 years while controlling for sensory processing. Twenty-four children, ages 73-112 months (S.D. = 11.4), diagnosed with high functioning ASD were assessed with the Wisconsin Card Sorting Test. Their teachers…

  2. Optochemical Activation of Kinase Function in Live Cells

    PubMed Central

    Karginov, Andrei V.; Hahn, Klaus M.; Deiters, Alexander

    2015-01-01

    Summary Manipulation of protein kinase activity is widely used to dissect signaling pathways controlling physiological and pathological processes. Common methods often cannot provide the desired spatial and temporal resolution in control of kinase activity. Regulation of kinase activity by photocaged kinase inhibitors has been successfully used to achieve tight temporal and local control, but inhibitors are limited to inactivation of kinases, and often do not provide the desired specificity. Here we report detailed methods for light-mediated activation of kinases in living cells using engineered rapamycin-regulated kinases (RapR-kinases) in conjunction with a photocaged analog of rapamycin. PMID:24718793

  3. 24 CFR 4100.1 - Functions and activities.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... and amenities, and improve the neighborhood's image and the functioning of its real estate market are... bodies providing financing. (B) The Owner Rehab Housing program assists low to moderate income...

  4. 24 CFR 4100.1 - Functions and activities.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... and amenities, and improve the neighborhood's image and the functioning of its real estate market are... bodies providing financing. (B) The Owner Rehab Housing program assists low to moderate income...

  5. 24 CFR 4100.1 - Functions and activities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and amenities, and improve the neighborhood's image and the functioning of its real estate market are... bodies providing financing. (B) The Owner Rehab Housing program assists low to moderate income...

  6. 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.

  7. Adsorption of 2,4,6-trinitrotoluene on the ZnO (21xAF1xAF0) surface: A density functional theory study of the detection mechanism of ZnO nanowire chemiresistors

    NASA Astrophysics Data System (ADS)

    Alnemrat, Sufian; Brett, Gary T.; Hooper, Joseph P.

    2013-10-01

    We report first-principles calculations of the adsorption of 2,4,6-trinitrotoluene (TNT), a prototypical nitroaromatic explosive, on the ZnO (21¯1¯0) surface. This surface is common among ZnO chemiresistors being considered for trace explosive detection. Recent work has achieved 60 ppb detection of TNT using a ZnO nanowire array, but the physical mechanism of sensing is unclear. Our results indicate that TNT strongly chemisorbs via interactions between the oxygen on the nitro groups and surface zinc, creating surface states within the gap. We present a theoretical estimate showing the strong effect of these surface states on the depletion layer of ZnO nanowires.

  8. 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.

  9. [Functional cerebral activity in a state of rest: connectivity networks].

    PubMed

    Proal, Erika; Alvarez-Segura, Mar; de la Iglesia-Vayá, María; Martí-Bonmatí, Luis; Castellanos, F Xavier

    2011-03-01

    Functional connectivity can be measured during task-based functional magnetic resonance imaging (fMRI), or in the absence of specific stimuli or tasks. In either case, the study of low frequency fluctuations in the BOLD signal reveals patterns of synchronization which delineate the intrinsic functional architecture of the brain. The scientific community now has available shared resources to accelerate the exploitation of resting state fMRI with the objectives of improving diagnostic methods and leading to better treatments grounded in neuroscience. Fomenting a collaborative scientific culture will accelerate our understanding of the underlying phenonmemna. Recently, the Spanish Resting State Network (SRSN) has joined this collaborative effort by creating a setting to facilitate collaboration among the various neuroscience research groups working in Spanish (http://www.nitrc.org/projects/srsn). PMID:21365601

  10. 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.

  11. Catalytic activities of platinum nanotubes: a density functional study

    NASA Astrophysics Data System (ADS)

    Mukherjee, Prajna; Gupta, Bikash C.; Jena, Puru

    2015-10-01

    In this work we investigate the catalytic properties of platinum nanotubes using density functional theory based calculations. In particular, we study the dissociation of hydrogen and oxygen molecules as well as oxidation of CO molecules. The results indicate that platinum nanotubes have good catalytic properties and can be effectively used in converting CO molecule to CO2.

  12. Towards computational prediction of microRNA function and activity

    PubMed Central

    Ulitsky, Igor; Laurent, Louise C.; Shamir, Ron

    2010-01-01

    While it has been established that microRNAs (miRNAs) play key roles throughout development and are dysregulated in many human pathologies, the specific processes and pathways regulated by individual miRNAs are mostly unknown. Here, we use computational target predictions in order to automatically infer the processes affected by human miRNAs. Our approach improves upon standard statistical tools by addressing specific characteristics of miRNA regulation. Our analysis is based on a novel compendium of experimentally verified miRNA-pathway and miRNA-process associations that we constructed, which can be a useful resource by itself. Our method also predicts novel miRNA-regulated pathways, refines the annotation of miRNAs for which only crude functions are known, and assigns differential functions to miRNAs with closely related sequences. Applying our approach to groups of co-expressed genes allows us to identify miRNAs and genomic miRNA clusters with functional importance in specific stages of early human development. A full list of the predicted mRNA functions is available at http://acgt.cs.tau.ac.il/fame/. PMID:20576699

  13. 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

  14. 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...

  15. Time delays and capability of elderly to activate speaker function for continuous telephone CPR

    PubMed Central

    2013-01-01

    Background Telephone-CPR (T-CPR) can increase rate of bystander CPR as well as CPR quality. Instructions for T-CPR were developed when most callers used a land line. Telephones today are often wireless and can be brought to the patient. They often have speaker function which further allows the rescuer to receive instructions while performing CPR. We wanted to measure adult lay people’s ability to activate the speaker function on their own mobile phone. Methods Elderly lay people, previously trained in CPR, were contacted by telephone. Participants with speaker function experience were asked to activate this without further instructions, while participants with no experience were given instructions on how to activate it. Participants were divided in three groups; Group 1: Can activate the speaker function without instruction, Group 2: Can activate the speaker function with instruction, and Group 3: Unable to activate the speaker function. Time to activation for group 1 and 2 was compared using Mann-Whitney U-test. Results Seventy-two elderly lay people, mean age 68 ± 6 years participated in the study. Thirty-five (35)% of the participants were able to activate the speaker function without instructions, 29% with instructions and 36% were unable to activate the speaker function. The median time to activate the speaker function was 8s and 93s, with and without instructions, respectively (p < 0.01). Conclusion One-third of the elderly could activate speaker function quickly, and two-third either used a long time or could not activate the function. PMID:23676015

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. Temporal Dynamics of Activation of Thematic and Functional Knowledge During Conceptual Processing of Manipulable Artifacts

    PubMed Central

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

    2012-01-01

    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. PMID:22449134

  1. 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.

  2. Emergent Public Spaces: Generative Activities on Function Interpolation

    ERIC Educational Resources Information Center

    Carmona, Guadalupe; Dominguez, Angeles; Krause, Gladys; Duran, Pablo

    2011-01-01

    This study highlights ways in which generative activities may be coupled with network-based technologies in the context of teacher preparation to enhance preservice teachers' cognizance of how their own experience as students provides a blueprint for the learning environments they may need to generate in their future classrooms. In this study, the…

  3. The effect of ageing on platelet function and fibrinolytic activity.

    PubMed

    Gleerup, G; Winther, K

    1995-08-01

    Twelve healthy male volunteers, mean age twenty-five, range twenty-one to thirty years, and 12 healthy middle-aged male volunteers mean age fifty-eight, range forty-four to seventy-two years, were tested regarding platelet aggregation induced by adenosine diphosphate and fibrinolytic activity, estimated as euglobulin clot lysis time (ECLT), tissue plasminogen activator (t-PA), and the fast-acting inhibitor against t-PA normally referred to as (PAI-1). Platelet aggregation increased significantly in the middle-aged group as compared with the young, as shown by a decrease in ADP thresholds for irreversible aggregation (P < 0.01). In healthy young volunteers, vigorous cycling exercise by itself caused platelet aggregability to decrease (P < 0.05). Such changes were not observed in the elderly. Fibrinolytic activity decreased significantly in the middle-aged group as shown by a prolongation of the ECLT (P < 0.01) and PAI-1, although not significantly, increased by approximately 100%, whereas t-PA significantly increased in the middle-aged group (P < 0.01). The present results suggest that increasing age is associated with not only increased platelet aggregability but also decreased fibrinolytic activity.

  4. 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...

  5. 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

  6. How to Make an Active Zone: Unexpected Universal Functional Redundancy between RIMs and RIM-BPs.

    PubMed

    Acuna, Claudio; Liu, Xinran; Südhof, Thomas C

    2016-08-17

    RIMs and RIM-binding proteins (RBPs) are evolutionary conserved multidomain proteins of presynaptic active zones that are known to recruit Ca(2+) channels; in addition, RIMs perform well-recognized functions in tethering and priming synaptic vesicles for exocytosis. However, deletions of RIMs or RBPs in mice cause only partial impairments in various active zone functions and have no effect on active zone structure, as visualized by electron micrographs, suggesting that their contribution to active zone functions is limited. Here, we show in synapses of the calyx of Held in vivo and hippocampal neurons in culture that combined, but not individual, deletions of RIMs and RBPs eliminate tethering and priming of synaptic vesicles, deplete presynaptic Ca(2+) channels, and ablate active zone complexes, as analyzed by electron microscopy of chemically fixed synapses. Thus, RBPs perform unexpectedly broad roles at the active zone that together with those of RIMs are essential for all active zone functions. PMID:27537484

  7. How to Make an Active Zone: Unexpected Universal Functional Redundancy between RIMs and RIM-BPs.

    PubMed

    Acuna, Claudio; Liu, Xinran; Südhof, Thomas C

    2016-08-17

    RIMs and RIM-binding proteins (RBPs) are evolutionary conserved multidomain proteins of presynaptic active zones that are known to recruit Ca(2+) channels; in addition, RIMs perform well-recognized functions in tethering and priming synaptic vesicles for exocytosis. However, deletions of RIMs or RBPs in mice cause only partial impairments in various active zone functions and have no effect on active zone structure, as visualized by electron micrographs, suggesting that their contribution to active zone functions is limited. Here, we show in synapses of the calyx of Held in vivo and hippocampal neurons in culture that combined, but not individual, deletions of RIMs and RBPs eliminate tethering and priming of synaptic vesicles, deplete presynaptic Ca(2+) channels, and ablate active zone complexes, as analyzed by electron microscopy of chemically fixed synapses. Thus, RBPs perform unexpectedly broad roles at the active zone that together with those of RIMs are essential for all active zone functions.

  8. Functionalization, cyclization and antiviral activity of A-secotriterpenoids.

    PubMed

    Grishko, Victoria V; Galaiko, Natalia V; Tolmacheva, Irina A; Kucherov, Igor I; Eremin, Vladimir F; Boreko, Eugene I; Savinova, Olga V; Slepukhin, Pavel A

    2014-08-18

    Triterpene derivatives with an α,β-alkenenitrile moiety in the five-membered ring A have been synthesized by nitrile anion cyclizations of 1-cyano-2,3-secotriterpenoids. Oxime-containing precursors, 2,3-secointermediates and five-membered ring A products of cyclizations were screened for in vitro antiviral activity against enveloped viruses - influenza A virus and human immunodeficiency virus type I (HIV-1). Lupane ketoxime and the 2,3-secolupane C-3 aldoxime which possess antiviral activities against both influenza A virus (EC50 12.9-18.2 μM) and HIV-1 (EC50 0.06 μM) were the most promising compounds. PMID:24997292

  9. Characterization of functionally active subribosomal particles from Thermus aquaticus

    PubMed Central

    Khaitovich, Philipp; Mankin, Alexander S.; Green, Rachel; Lancaster, Laura; Noller, Harry F.

    1999-01-01

    Peptidyl transferase activity of Thermus aquaticus ribosomes is resistant to the removal of a significant number of ribosomal proteins by protease digestion, SDS, and phenol extraction. To define the upper limit for the number of macromolecular components required for peptidyl transferase, particles obtained by extraction of T. aquaticus large ribosomal subunits were isolated and their RNA and protein composition was characterized. Active subribosomal particles contained both 23S and 5S rRNA associated with notable amounts of eight ribosomal proteins. N-terminal sequencing of the proteins identified them as L2, L3, L13, L15, L17, L18, L21, and L22. Ribosomal protein L4, which previously was thought to be essential for the reconstitution of particles active in peptide bond formation, was not found. These findings, together with the results of previous reconstitution experiments, reduce the number of possible essential macromolecular components of the peptidyl transferase center to 23S rRNA and ribosomal proteins L2 and L3. Complete removal of ribosomal proteins from T. aquaticus rRNA resulted in loss of tertiary folding of the particles and inactivation of peptidyl transferase. The accessibility of proteins in active subribosomal particles to proteinase hydrolysis was increased significantly after RNase treatment. These results and the observation that 50S ribosomal subunits exhibited much higher resistance to SDS extraction than 30S subunits are compatible with a proposed structural organization of the 50S subunit involving an RNA “cage” surrounding a core of a subset of ribosomal proteins. PMID:9874776

  10. 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.

  11. Fluctuations in Neuronal Activity: Clues to Brain Function

    NASA Astrophysics Data System (ADS)

    Pérez Velazquez, José L.; Guevara, Ramón; Belkas, Jason; Wennberg, Richard; Senjanoviè, Goran; García Dominguez, Luis

    2005-08-01

    Recordings from neuronal preparations, either in vitro or in the intact brain, are characterized by fluctuations, what is commonly considered as "noise". Due to the current recording and analysis methods, it is not feasible to separate what we term noise, from the "meaningful" neuronal activity. We propose that fluctuations serve to maintain brain activity in an optimal state for cognitive processing, not allowing it to fall into long-term periodic behaviour. We have studied fluctuations in magnetoencephalographic (MEG) recordings from normal subjects and epileptic patients, in electroencephalographic (EEG) recordings from children with impact injury, as well as in intracerebral electrophysiological recordings in freely moving rats. Specifically, we have determined phase locking patterns between brain areas from these recordings, which display fluctuations at different scales. We submit the idea that the variability in phase synchronization affords a more complete search of all possible phase differences in a hypothetical phase-locking state space that contributes to brain information processing. In brain pathologies, like epileptiform activity here studied, different levels of fluctuations in phase synchrony may favour the generation of stable synchronized states that characterize epileptic seizures. While the border between noise and high-dimensional dynamics is fuzzy, the scrutiny of neuronal fluctuations at different levels will provide important insights to the unravelling of the relation between brain and behaviour.

  12. Diverse Activities of Histone Acylations Connect Metabolism to Chromatin Function.

    PubMed

    Dutta, Arnob; Abmayr, Susan M; Workman, Jerry L

    2016-08-18

    Modifications of histones play important roles in balancing transcriptional output. The discovery of acyl marks, besides histone acetylation, has added to the functional diversity of histone modifications. Since all modifications use metabolic intermediates as substrates for chromatin-modifying enzymes, the prevalent landscape of histone modifications in any cell type is a snapshot of its metabolic status. Here, we review some of the current findings of how differential use of histone acylations regulates gene expression as response to metabolic changes and differentiation programs. PMID:27540855

  13. The nuclear factor SPBP contains different functional domains and stimulates the activity of various transcriptional activators.

    PubMed

    Rekdal, C; Sjøttem, E; Johansen, T

    2000-12-22

    SPBP (stromelysin-1 platelet-derived growth factor-responsive element binding protein) was originally cloned from a cDNA expression library by virtue of its ability to bind to a platelet-derived growth factor-responsive element in the human stromelysin-1 promoter. A 937-amino acid-long protein was deduced from a 3995-nucleotide murine cDNA sequence. By analyses of both human and murine cDNAs, we now show that SPBP is twice as large as originally found. The human SPBP gene contains six exons and is located on chromosome 22q13.1-13.3. Two isoforms differing in their C termini are expressed due to alternative splicing. PCR analyses of multitissue cDNA panels showed that SPBP is expressed in most tissues except for ovary and prostate. Functional mapping revealed that SPBP is a nuclear, multidomain protein containing an N-terminal region with transactivating ability, a novel type of DNA-binding domain containing an AT hook motif, and a bipartite nuclear localization signal as well as a C-terminal zinc finger domain. This type of zinc finger domain is also found in the trithorax family of chromatin-based transcriptional regulator proteins. Using cotransfection experiments, we find that SPBP enhances the transcriptional activity of various transcription factors such as c-Jun, Ets1, Sp1, and Pax6. Hence, SPBP seems to act as a transcriptional coactivator. PMID:10995766

  14. Promoter-dependent activity on androgen receptor N-terminal domain mutations in androgen insensitivity syndrome.

    PubMed

    Tadokoro-Cuccaro, Rieko; Davies, John; Mongan, Nigel P; Bunch, Trevor; Brown, Rosalind S; Audi, Laura; Watt, Kate; McEwan, Iain J; Hughes, Ieuan A

    2014-01-01

    Androgen receptor (AR) mutations are associated with androgen insensitivity syndrome (AIS). Missense mutations identified in the AR-N-terminal domain (AR-NTD) are rare, and clinical phenotypes are typically mild. We investigated 7 missense mutations and 2 insertion/deletions located in the AR-NTD. This study aimed to elucidate the pathogenic role of AR-NTD mutants in AIS and to use this knowledge to further define AR-NTD function. AR-NTD mutations (Q120E, A159T, G216R, N235K, G248V, L272F, and P380R) were introduced into AR-expression plasmids. Stably expressing cell lines were established for del57L and ins58L. Transactivation was measured using luciferase reporter constructs under the control of GRE and Pem promoters. Intrinsic fluorescence spectroscopy and partial proteolysis studies were performed for mutations which showed reduced activities by using a purified AR-AF1 protein. Pem-luciferase reporter activation was reduced for A159T, N235K, and G248V but not the GRE-luciferase reporter. Protein structure analysis detected no significant change in the AR-AF1 region for these mutations. Reduced cellular expression and transactivation activity were observed for ins58L. The mutations Q120E, G216R, L272F, P380R, and del57L showed small or no detectable changes in function. Thus, clinical and experimental analyses have identified novel AR-signalling defects associated with mutations in the structurally disordered AR-NTD domain in patients with AIS.

  15. Physical Activity Play: The Nature and Function of a Neglected Aspect of Play.

    ERIC Educational Resources Information Center

    Pellegrini, A. D.; Smith, Peter K.

    1998-01-01

    Considers the nature and developmental functions of physical activity play. Distinguishes three kinds of physical activity play with consecutive age peaks: rhythmic stereotypies, exercise play, and rough-and-tumble play. Considers gender differences and function in terms of immediate and deferred consequences in physical, cognitive, and social…

  16. Activation-Enabled Syntheses of Functionalized Pillar[5]arene Derivatives.

    PubMed

    Han, Jie; Hou, Xisen; Ke, Chenfeng; Zhang, Huacheng; Strutt, Nathan L; Stern, Charlotte L; Stoddart, J Fraser

    2015-07-01

    A series of regioselective di- and trifunctionalized pillar[5]arene derivatives have been synthesized by a deprotection-followed-by-activation strategy, and their constitutions have been established as a result of having access to their solid-state structures. De-O-methylation occurs in a stepwise manner at lower temperatures under kinetic control, affording the desired oligo-substituted pillar[5]arene derivatives. In addition, the regioisomers of these derivatives can be isolated by installing triflate groups on the free hydroxyl groups. PMID:26083303

  17. [The brain structures functional activity and aggression patients' multiple sclerosis].

    PubMed

    Reznikova, T N; Seliverstova, N A; Kataeva, G V; Aroev, R A; Il'ves, A G; Kuznetsova, A K

    2015-01-01

    The article is devoted to investigation of unconscious aggression in patients with multiple sclerosis. We carried out comparison of the relative assessments of metabolism speed of glucose (according to positron emission tomography) and indicators of unconscious aggression (in the Hand test). It is shown that an increased tendency to open aggression (unconscious aggression) in patients with multiple sclerosis, is mainly linked with a reduction in the functioning of different departments of the frontal lobes of the brain on the left and with changes of the metabolism speed of glucose in the structures of the limbic system of the left and right hemisphere. With increasing of unconscious aggression we observed decrease of glucose metabolism speed in certain areas of the lower and middle frontal gyrus.

  18. Interferon-γ activation of polymorphonuclear neutrophil function

    PubMed Central

    Ellis, Terri N; Beaman, Blaine L

    2004-01-01

    As current research illuminates the dynamic interplay between the innate and acquired immune responses, the interaction and communication between these two arms has yet to be fully investigated. Polymorphonuclear neutrophils (PMNs) and interferon-γ (IFN-γ) are known critical components of innate and acquired immunity, respectively. However, recent studies have demonstrated that these two components are not entirely isolated. Treatment of PMNs with IFN-γ elicits a variety of responses depending on stimuli and environmental conditions. These responses include increased oxidative burst, differential gene expression, and induction of antigen presentation. Many of these functions have been overlooked in PMNs, which have long been classified as terminal phagocytic cells incapable of protein synthesis. As this review reports, the old definition of the PMN is in need of an update, as these cells have demonstrated their ability to mediate the transition between the innate and acquired immune responses. PMID:15096178

  19. Functionally relevant diversity of closely related Nitrospira in activated sludge

    PubMed Central

    Gruber-Dorninger, Christiane; Pester, Michael; Kitzinger, Katharina; Savio, Domenico F; Loy, Alexander; Rattei, Thomas; Wagner, Michael; Daims, Holger

    2015-01-01

    Nitrospira are chemolithoautotrophic nitrite-oxidizing bacteria that catalyze the second step of nitrification in most oxic habitats and are important for excess nitrogen removal from sewage in wastewater treatment plants (WWTPs). To date, little is known about their diversity and ecological niche partitioning within complex communities. In this study, the fine-scale community structure and function of Nitrospira was analyzed in two full-scale WWTPs as model ecosystems. In Nitrospira-specific 16S rRNA clone libraries retrieved from each plant, closely related phylogenetic clusters (16S rRNA identities between clusters ranged from 95.8% to 99.6%) within Nitrospira lineages I and II were found. Newly designed probes for fluorescence in situ hybridization (FISH) allowed the specific detection of several of these clusters, whose coexistence in the WWTPs was shown for prolonged periods of several years. In situ ecophysiological analyses based on FISH, relative abundance and spatial arrangement quantification, as well as microautoradiography revealed functional differences of these Nitrospira clusters regarding the preferred nitrite concentration, the utilization of formate as substrate and the spatial coaggregation with ammonia-oxidizing bacteria as symbiotic partners. Amplicon pyrosequencing of the nxrB gene, which encodes subunit beta of nitrite oxidoreductase of Nitrospira, revealed in one of the WWTPs as many as 121 species-level nxrB operational taxonomic units with highly uneven relative abundances in the amplicon library. These results show a previously unrecognized high diversity of Nitrospira in engineered systems, which is at least partially linked to niche differentiation and may have important implications for process stability. PMID:25148481

  20. Functionally relevant diversity of closely related Nitrospira in activated sludge.

    PubMed

    Gruber-Dorninger, Christiane; Pester, Michael; Kitzinger, Katharina; Savio, Domenico F; Loy, Alexander; Rattei, Thomas; Wagner, Michael; Daims, Holger

    2015-03-01

    Nitrospira are chemolithoautotrophic nitrite-oxidizing bacteria that catalyze the second step of nitrification in most oxic habitats and are important for excess nitrogen removal from sewage in wastewater treatment plants (WWTPs). To date, little is known about their diversity and ecological niche partitioning within complex communities. In this study, the fine-scale community structure and function of Nitrospira was analyzed in two full-scale WWTPs as model ecosystems. In Nitrospira-specific 16S rRNA clone libraries retrieved from each plant, closely related phylogenetic clusters (16S rRNA identities between clusters ranged from 95.8% to 99.6%) within Nitrospira lineages I and II were found. Newly designed probes for fluorescence in situ hybridization (FISH) allowed the specific detection of several of these clusters, whose coexistence in the WWTPs was shown for prolonged periods of several years. In situ ecophysiological analyses based on FISH, relative abundance and spatial arrangement quantification, as well as microautoradiography revealed functional differences of these Nitrospira clusters regarding the preferred nitrite concentration, the utilization of formate as substrate and the spatial coaggregation with ammonia-oxidizing bacteria as symbiotic partners. Amplicon pyrosequencing of the nxrB gene, which encodes subunit beta of nitrite oxidoreductase of Nitrospira, revealed in one of the WWTPs as many as 121 species-level nxrB operational taxonomic units with highly uneven relative abundances in the amplicon library. These results show a previously unrecognized high diversity of Nitrospira in engineered systems, which is at least partially linked to niche differentiation and may have important implications for process stability. PMID:25148481

  1. Feelings of well being in elderly people: relationship to physical activity and physical function.

    PubMed

    Garatachea, Nuria; Molinero, Olga; Martínez-García, Raquel; Jiménez-Jiménez, Rodrigo; González-Gallego, Javier; Márquez, Sara

    2009-01-01

    The aim of the research was to investigate in a sample of Spanish elderly whether measures of physical activity and physical function are related to feelings of well being, and whether level of dependence is a moderator in the relation of well being, physical activity and physical function. The sample was a cohort of 151 elderly people (89 women and 62 men, aged 60-98 years) from the North of Spain. Participants completed surveys including demographic characteristics, and measures of physical activity (Yale Physical Activity Survey, YPAS), instrumental activities of daily living (Barthel Index, BI) and well being (Psychological Well Being Scale, from Spanish: Escala de Bienestar Psicológico=EBP). Components of the physical function were measured by the Senior Fitness Test (SFT). Upper and lower body strength, dynamic balance, aerobic endurance, self-reported weekly energy expenditure and physical activity total time were significantly correlated with both Material and Subjective well being. All components of physical function were significantly impaired in dependent subjects when compared to independent individuals of the same sex and physical activity category. Significant differences were also observed in Subjective well being among less active dependent or independent individuals. In conclusion, physical function and physical activity are related to feelings of well being, and results emphasize the positive functional and psychological effects of physical activity in dependent subjects.

  2. 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…

  3. A new approach to the determination of the stellate neuron activity function in rat's brain

    NASA Astrophysics Data System (ADS)

    Klymenko, O.; Oleinick, A.; Amatore, C.; Svir, I.

    2008-09-01

    In this work, we present the results of a mathematical modelling of NO· release by neurons and its transport in the brain by diffusion. The model is applied to analyze the experimental data on NO· release from a neuron monitored during its patch-clamp stimulation by an ultramicroelectrode introduced into a slice of living rat’s brain. The neuron activity function was obtained by numerical deconvolution of the experimental data using the response function of the electrode to an instantaneous spike of neuronal activity. The Gaussian decomposition of NO· release activity function allows qualitative and quantitative conclusions to be drawn about neuron activity. Since the integral activity function is readily obtained by deconvolution, the decomposition can be performed using other more relevant descriptions of NO· bursts emerging from active neurons.

  4. Sympathetic Activation and Baroreflex Function during Intradialytic Hypertensive Episodes

    PubMed Central

    Rubinger, Dvora; Backenroth, Rebecca; Sapoznikov, Dan

    2012-01-01

    Background The mechanisms of intradialytic increases in blood pressure are not well defined. The present study was undertaken to assess the role of autonomic nervous system activation during intradialytic hypertensive episodes. Methodology/Principal Findings Continuous interbeat intervals (IBI) and systolic blood pressure (SBP) were monitored during hemodialysis in 108 chronic patients. Intradialytic hypertensive episodes defined as a period of at least 10 mmHg increase in SBP between the beginning and the end of a dialysis session or hypertension resistant to ultrafiltration occurring during or immediately after the dialysis procedure, were detected in 62 out of 113 hemodialysis sessions. SBP variability, IBI variability and baroreceptor sensitivity (BRS) in the low (LF) and high (HF) frequency ranges were assessed using the complex demodulation technique (CDM). Intradialytic hypertensive episodes were associated with an increased (n = 45) or decreased (n = 17) heart rate. The maximal blood pressure was similar in both groups. In patients with increased heart rate the increase in blood pressure was associated with marked increases in SBP and IBI variability, with suppressed BRS indices and enhanced sympatho-vagal balance. In contrast, in those with decreased heart rate, there were no significant changes in the above parameters. End-of- dialysis blood pressure in all sessions associated with hypertensive episode was significantly higher than in those without such episodes. In logistic regression analysis, predialysis BRS in the low frequency range was found to be the main predictor of intradialytic hypertension. Conclusion/Significance Our data point to sympathetic overactivity with feed-forward blood pressure enhancement as an important mechanism of intradialytic hypertension in a significant proportion of patients. The triggers of increased sympathetic activity during hemodialysis remain to be determined. Intradialytic hypertensive episodes are associated

  5. 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.

  6. 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

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

    PubMed

    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

  8. Functional School Activities I. Functional Programming for People with Autism: A Series.

    ERIC Educational Resources Information Center

    Dalrymple, Nancy; Porco, Barbara

    The educational program of a student with autism most easily and beneficially begins with manipulation of objects. Short periods of time should be allotted to each activity to hold attention and ensure success. Partial participation and an individualized reinforcement schedule are important elements in the instructional design. Assistance in…

  9. 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…

  10. The effects of physical activity on functional MRI activation associated with cognitive control in children: a randomized controlled intervention

    PubMed Central

    Chaddock-Heyman, Laura; Erickson, Kirk I.; Voss, Michelle W.; Knecht, Anya M.; Pontifex, Matthew B.; Castelli, Darla M.; Hillman, Charles H.; Kramer, Arthur F.

    2013-01-01

    This study used functional magnetic resonance imaging (fMRI) to examine the influence of a 9-month physical activity program on task-evoked brain activation during childhood. The results demonstrated that 8- to 9-year-old children who participated in 60+ min of physical activity, 5 days per week, for 9 months, showed decreases in fMRI brain activation in the right anterior prefrontal cortex coupled with within-group improvements in performance on a task of attentional and interference control. Children assigned to a wait-list control group did not show changes in brain function. Furthermore, at post-test, children in the physical activity group showed similar anterior frontal brain patterns and incongruent accuracy rates to a group of college-aged young adults. Children in the wait-list control group still differed from the young adults in terms of anterior prefrontal activation and performance at post-test. There were no significant changes in fMRI activation in the anterior cingulate cortex (ACC) for either group. These results suggest that physical activity during childhood may enhance specific elements of prefrontal cortex function involved in cognitive control. PMID:23487583

  11. 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

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

    2014-10-01

    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

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

    PubMed

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

    2015-07-02

    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.

  13. Docosahexaenoic acid modulates inflammatory and antineurogenic functions of activated microglial cells.

    PubMed

    Antonietta Ajmone-Cat, Maria; Lavinia Salvatori, Maria; De Simone, Roberta; Mancini, Melissa; Biagioni, Stefano; Bernardo, Antonietta; Cacci, Emanuele; Minghetti, Luisa

    2012-03-01

    The complex process of microglial activation encompasses several functional activation states associated either with neurotoxic/antineurogenic or with neurotrophic/proneurogenic properties, depending mainly on the extent of activation and the nature of the activating stimuli. Several studies have demonstrated that acute exposure to the prototypical activating agent lipopolysaccharide (LPS) confers antineurogenic properties upon microglial cells. Acutely activated microglia ortheir conditioned media (CM) reduce neural stem progenitor cell (NPC) survival and prevent NPC differentiation into neurons. The present study tested the hypothesis that docosahexaenoic acid (DHA), a long-chain polyunsatured fatty acid (L-PUFA) with potent immunomodulatory properties, could dampen microglial proinflammatory functions and modulate their antineurogenic effect. We demonstrate that DHA dose dependently inhibits the synthesis of inflammatory products in activated microglia without inducing an alternative antiinflammatory phenotype. Among the possible DHA mechanisms of action, we propose the inhibition of p38 MAPK phosphorylation and the activation of the nuclear receptor peroxisome proliferator activated receptor (PPAR)-γ. The attenuation of M1 proinflammatory phenotype has relevant consequences for the survival and differentiation of NPC, because DHA reverses the antineurogenic activities of conditioned media from LPS-activated microglia. Our study identifies new relevant potentially protective and proneurogenic functions of DHA, exerted through the modulation of microglial functions, that could be exploited to sustain or promote neuroregenerative processes in damaged/aged brain. PMID:22057807

  14. Oxidative Dehydrogenation on Nanocarbon: Intrinsic Catalytic Activity and Structure-Function Relationships.

    PubMed

    Qi, Wei; Liu, Wei; Guo, Xiaoling; Schlögl, Robert; Su, Dangsheng

    2015-11-01

    Physical and chemical insights into the nature and quantity of the active sites and the intrinsic catalytic activity of nanocarbon materials in alkane oxidative dehydrogenation (ODH) reactions are reported using a novel in situ chemical titration process. A study on the structure-function relationship reveals that the active sites are identical both in nature and function on various nanocarbon catalysts. Additionally, the quantity of the active sites could be used as a metric to normalize the reaction rates, and thus to evaluate the intrinsic activity of nanocarbon catalysts. The morphology of the nanocarbon catalysts at the microscopic scale exhibits a minor influence on their intrinsic ODH catalytic activity. The number of active sites calculated from the titration process indicates the number of catalytic centers that are active (that is, working) under the reaction conditions. PMID:26388451

  15. 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.

  16. 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.

  17. Extracellular protein analysis of activated sludge and their functions in wastewater treatment plant by shotgun proteomics

    PubMed Central

    Zhang, Peng; Shen, Yu; Guo, Jin-Song; Li, Chun; Wang, Han; Chen, You-Peng; Yan, Peng; Yang, Ji-Xiang; Fang, Fang

    2015-01-01

    In this work, proteins in extracellular polymeric substances extracted from anaerobic, anoxic and aerobic sludges of wastewater treatment plant (WWTP) were analyzed to probe their origins and functions. Extracellular proteins in WWTP sludges were identified using shotgun proteomics, and 130, 108 and 114 proteins in anaerobic, anoxic and aerobic samples were classified, respectively. Most proteins originated from cell and cell part, and their most major molecular functions were catalytic activity and binding activity. The results exhibited that the main roles of extracellular proteins in activated sludges were multivalence cations and organic molecules binding, as well as in catalysis and degradation. The catalytic activity proteins were more widespread in anaerobic sludge compared with those in anoxic and aerobic sludges. The structure difference between anaerobic and aerobic sludges could be associated with their catalytic activities proteins. The results also put forward a relation between the macro characteristics of activated sludges and micro functions of extracellular proteins in biological wastewater treatment process. PMID:26160685

  18. 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.

  19. Identifying active functionalities on few-layered graphene catalysts for oxidative dehydrogenation of isobutane.

    PubMed

    Dathar, Gopi Krishna Phani; Tsai, Yu-Tung; Gierszal, Kamil; Xu, Ye; Liang, Chengdu; Rondinone, Adam J; Overbury, Steven H; Schwartz, Viviane

    2014-02-01

    The general consensus in the studies of nanostructured carbon catalysts for oxidative dehydrogenation (ODH) of alkanes to olefins is that the oxygen functionalities generated during synthesis and reaction are responsible for the catalytic activity of these nanostructured carbons. Identification of the highly active oxygen functionalities would enable engineering of nanocarbons for ODH of alkanes. Few-layered graphenes were used as model catalysts in experiments to synthesize reduced graphene oxide samples with varying oxygen concentrations, to characterize oxygen functionalities, and to measure the activation energies for ODH of isobutane. Periodic density functional theory calculations were performed on graphene nanoribbon models with a variety of oxygen functionalities at the edges to calculate their thermal stability and to model reaction mechanisms for ODH of isobutane. Comparing measured and calculated thermal stability and activation energies leads to the conclusion that dicarbonyls at the zigzag edges and quinones at armchair edges are appropriately balanced for high activity, relative to other model functionalities considered herein. In the ODH of isobutane, both dehydrogenation and regeneration of catalytic sites are relevant at the dicarbonyls, whereas regeneration is facile compared with dehydrogenation at quinones. The catalytic mechanism involves weakly adsorbed isobutane reducing functional oxygen and leaving as isobutene, and O2 in the feed, weakly adsorbed on the hydrogenated functionality, reacting with that hydrogen and regenerating the catalytic sites.

  20. 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.

  1. 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…

  2. 20 CFR 641.856 - What functions and activities constitute administrative costs?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... management, accounting, and payroll systems) including the purchase, systems development, and operating costs..., including: (i) Accounting, budgeting, financial, and cash management functions; (ii) Procurement and... carrying out administrative activities or the overall management of the program; (5) Costs of...

  3. Multistability and Instability of Neural Networks With Discontinuous Nonmonotonic Piecewise Linear Activation Functions.

    PubMed

    Nie, Xiaobing; Zheng, Wei Xing

    2015-11-01

    In this paper, we discuss the coexistence and dynamical behaviors of multiple equilibrium points for recurrent neural networks with a class of discontinuous nonmonotonic piecewise linear activation functions. It is proved that under some conditions, such n -neuron neural networks can have at least 5(n) equilibrium points, 3(n) of which are locally stable and the others are unstable, based on the contraction mapping theorem and the theory of strict diagonal dominance matrix. The investigation shows that the neural networks with the discontinuous activation functions introduced in this paper can have both more total equilibrium points and more locally stable equilibrium points than the ones with continuous Mexican-hat-type activation function or discontinuous two-level activation functions. An illustrative example with computer simulations is presented to verify the theoretical analysis.

  4. 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.

  5. Function-based classification of carbohydrate-active enzymes by recognition of short, conserved peptide motifs.

    PubMed

    Busk, Peter Kamp; Lange, Lene

    2013-06-01

    Functional prediction of carbohydrate-active enzymes is difficult due to low sequence identity. However, similar enzymes often share a few short motifs, e.g., around the active site, even when the overall sequences are very different. To exploit this notion for functional prediction of carbohydrate-active enzymes, we developed a simple algorithm, peptide pattern recognition (PPR), that can divide proteins into groups of sequences that share a set of short conserved sequences. When this method was used on 118 glycoside hydrolase 5 proteins with 9% average pairwise identity and representing four characterized enzymatic functions, 97% of the proteins were sorted into groups correlating with their enzymatic activity. Furthermore, we analyzed 8,138 glycoside hydrolase 13 proteins including 204 experimentally characterized enzymes with 28 different functions. There was a 91% correlation between group and enzyme activity. These results indicate that the function of carbohydrate-active enzymes can be predicted with high precision by finding short, conserved motifs in their sequences. The glycoside hydrolase 61 family is important for fungal biomass conversion, but only a few proteins of this family have been functionally characterized. Interestingly, PPR divided 743 glycoside hydrolase 61 proteins into 16 subfamilies useful for targeted investigation of the function of these proteins and pinpointed three conserved motifs with putative importance for enzyme activity. Furthermore, the conserved sequences were useful for cloning of new, subfamily-specific glycoside hydrolase 61 proteins from 14 fungi. In conclusion, identification of conserved sequence motifs is a new approach to sequence analysis that can predict carbohydrate-active enzyme functions with high precision. PMID:23524681

  6. Function-based classification of carbohydrate-active enzymes by recognition of short, conserved peptide motifs.

    PubMed

    Busk, Peter Kamp; Lange, Lene

    2013-06-01

    Functional prediction of carbohydrate-active enzymes is difficult due to low sequence identity. However, similar enzymes often share a few short motifs, e.g., around the active site, even when the overall sequences are very different. To exploit this notion for functional prediction of carbohydrate-active enzymes, we developed a simple algorithm, peptide pattern recognition (PPR), that can divide proteins into groups of sequences that share a set of short conserved sequences. When this method was used on 118 glycoside hydrolase 5 proteins with 9% average pairwise identity and representing four characterized enzymatic functions, 97% of the proteins were sorted into groups correlating with their enzymatic activity. Furthermore, we analyzed 8,138 glycoside hydrolase 13 proteins including 204 experimentally characterized enzymes with 28 different functions. There was a 91% correlation between group and enzyme activity. These results indicate that the function of carbohydrate-active enzymes can be predicted with high precision by finding short, conserved motifs in their sequences. The glycoside hydrolase 61 family is important for fungal biomass conversion, but only a few proteins of this family have been functionally characterized. Interestingly, PPR divided 743 glycoside hydrolase 61 proteins into 16 subfamilies useful for targeted investigation of the function of these proteins and pinpointed three conserved motifs with putative importance for enzyme activity. Furthermore, the conserved sequences were useful for cloning of new, subfamily-specific glycoside hydrolase 61 proteins from 14 fungi. In conclusion, identification of conserved sequence motifs is a new approach to sequence analysis that can predict carbohydrate-active enzyme functions with high precision.

  7. Muscle activity during functional coordination training: implications for strength gain and rehabilitation.

    PubMed

    Jørgensen, Marie B; Andersen, Lars L; Kirk, Niels; Pedersen, Mogens T; Søgaard, Karen; Holtermann, Andreas

    2010-07-01

    The purpose of this study was to evaluate if different types, body positions, and levels of progression of functional coordination exercises can provide sufficiently high levels of muscle activity to improve strength of the neck, shoulder, and trunk muscles. Nine untrained women were familiarized with 7 functional coordination exercises 12 times during 4 weeks before testing. Surface electromyographic (EMG) activity was obtained from rectus abdominus, erector spinae, obliquus externus, and trapezius during the exercises with 2-4 levels of progression. Electromyography was normalized to the maximal EMG activity during maximal voluntary contractions, and a p value < 0.05 was considered significant. All recorded muscles reached sufficiently high levels of activity during the coordination exercises for strength gain (>60% of maximal EMG activity). Type of exercise played a significant role for the attained muscle activity. Body position during the exercises was important for the activity of the erector spinae, and level of progression was important for the activity of the trapezius. The findings indicate that depending on type, body position, and level of progression, functional coordination training can be performed with a muscle activity sufficient for strength gain. Functional coordination training may therefore be a good choice for prevention or rehabilitation of musculoskeletal pain or injury in the neck, shoulder, or trunk muscles.

  8. Functional analysis of oxidative stress-activated mitogen-activated protein kinase cascade in plants

    PubMed Central

    Kovtun, Yelena; Chiu, Wan-Ling; Tena, Guillaume; Sheen, Jen

    2000-01-01

    Despite the recognition of H2O2 as a central signaling molecule in stress and wounding responses, pathogen defense, and regulation of cell cycle and cell death, little is known about how the H2O2 signal is perceived and transduced in plant cells. We report here that H2O2 is a potent activator of mitogen-activated protein kinases (MAPKs) in Arabidopsis leaf cells. Using epitope tagging and a protoplast transient expression assay, we show that H2O2 can activate a specific Arabidopsis mitogen-activated protein kinase kinase kinase, ANP1, which initiates a phosphorylation cascade involving two stress MAPKs, AtMPK3 and AtMPK6. Constitutively active ANP1 mimics the H2O2 effect and initiates the MAPK cascade that induces specific stress-responsive genes, but it blocks the action of auxin, a plant mitogen and growth hormone. The latter observation provides a molecular link between oxidative stress and auxin signal transduction. Finally, we show that transgenic tobacco plants that express a constitutively active tobacco ANP1 orthologue, NPK1, display enhanced tolerance to multiple environmental stress conditions without activating previously described drought, cold, and abscisic acid signaling pathways. Thus, manipulation of key regulators of an oxidative stress signaling pathway, such as ANP1/NPK1, provides a strategy for engineering multiple stress tolerance that may greatly benefit agriculture. PMID:10717008

  9. Distinct Developmental Functions of Prostasin (CAP1/PRSS8) Zymogen and Activated Prostasin.

    PubMed

    Friis, Stine; Madsen, Daniel H; Bugge, Thomas H

    2016-02-01

    The membrane-anchored serine prostasin (CAP1/PRSS8) is essential for barrier acquisition of the interfollicular epidermis and for normal hair follicle development. Consequently, prostasin null mice die shortly after birth. Prostasin is found in two forms in the epidermis: a one-chain zymogen and a two-chain proteolytically active form, generated by matriptase-dependent activation site cleavage. Here we used gene editing to generate mice expressing only activation site cleavage-resistant (zymogen-locked) endogenous prostasin. Interestingly, these mutant mice displayed normal interfollicular epidermal development and postnatal survival, but had defects in whisker and pelage hair formation. These findings identify two distinct in vivo functions of epidermal prostasin: a function in the interfollicular epidermis, not requiring activation site cleavage, that can be mediated by the zymogen-locked version of prostasin and a proteolysis-dependent function of activated prostasin in hair follicles, dependent on zymogen conversion by matriptase.

  10. Distinct Developmental Functions of Prostasin (CAP1/PRSS8) Zymogen and Activated Prostasin.

    PubMed

    Friis, Stine; Madsen, Daniel H; Bugge, Thomas H

    2016-02-01

    The membrane-anchored serine prostasin (CAP1/PRSS8) is essential for barrier acquisition of the interfollicular epidermis and for normal hair follicle development. Consequently, prostasin null mice die shortly after birth. Prostasin is found in two forms in the epidermis: a one-chain zymogen and a two-chain proteolytically active form, generated by matriptase-dependent activation site cleavage. Here we used gene editing to generate mice expressing only activation site cleavage-resistant (zymogen-locked) endogenous prostasin. Interestingly, these mutant mice displayed normal interfollicular epidermal development and postnatal survival, but had defects in whisker and pelage hair formation. These findings identify two distinct in vivo functions of epidermal prostasin: a function in the interfollicular epidermis, not requiring activation site cleavage, that can be mediated by the zymogen-locked version of prostasin and a proteolysis-dependent function of activated prostasin in hair follicles, dependent on zymogen conversion by matriptase. PMID:26719335

  11. 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. PMID:27401999

  12. 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.

  13. Using function-focused care to increase physical activity among older adults.

    PubMed

    Resnick, Barbara; Galik, Elizabeth

    2013-01-01

    Despite the known benefits of physical activity for older adults, adherence to regular physical activity recommendations is poor. Less than half of adults in this country meet physical activity recommendations with reasons for lack of adherence including such things as access, motivation, pain, fear, comorbidities, among others. To overcome these challenges, function-focused care was developed. Function-focused care is a philosophy of care that focuses on evaluating the older adult's underlying capability with regard to function and physical activity and helping him or her optimize and maintain physical function and ability and continually increase time spent in physical activity. Examples of function-focused care include such things as using verbal cues during bathing, so the older individual performs the tasks rather than the caregiver bathing the individual; walking a resident or patient to the bathroom rather than using a urinal, or taking a resident to an exercise class. There are now over 20 studies supporting the benefits of function-focused care approaches across all settings and different types of patient groups (i.e, those with mild versus moderate-to-severe cognitive impairment). The approaches for implementation of function-focused care have also been well supported and have moved beyond establishing effectiveness to considering dissemination and implementation of this approach into real world clinical settings. The process of dissemination and implementation has likewise been articulated and supported, and ongoing work needs to continue in this venue across all care settings. PMID:24894140

  14. 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.

  15. 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

  16. Diversity of dominant bacterial taxa in activated sludge promotes functional resistance following toxic shock loading.

    PubMed

    Saikaly, Pascal E; Oerther, Daniel B

    2011-04-01

    Examining the relationship between biodiversity and functional stability (resistance and resilience) of activated sludge bacterial communities following disturbance is an important first step towards developing strategies for the design of robust biological wastewater treatment systems. This study investigates the relationship between functional resistance and biodiversity of dominant bacterial taxa by subjecting activated sludge samples, with different levels of biodiversity, to toxic shock loading with cupric sulfate (Cu[II]), 3,5-dichlorophenol (3,5-DCP), or 4-nitrophenol (4-NP). Respirometric batch experiments were performed to determine the functional resistance of activated sludge bacterial community to the three toxicants. Functional resistance was estimated as the 30 min IC(50) or the concentration of toxicant that results in a 50% reduction in oxygen utilization rate compared to a referential state represented by a control receiving no toxicant. Biodiversity of dominant bacterial taxa was assessed using polymerase chain reaction-terminal restriction fragment length polymorphism (PCR-T-RFLP) targeting the 16S ribosomal RNA (16S rRNA) gene. Statistical analysis of 30 min IC(50) values and PCR-T-RFLP data showed a significant positive correlation (P < 0.05) between functional resistance and microbial diversity for each of the three toxicants tested. To our knowledge, this is the first study showing a positive correlation between biodiversity of dominant bacterial taxa in activated sludge and functional resistance. In this system, activated sludge bacterial communities with higher biodiversity are functionally more resistant to disturbance caused by toxic shock loading.

  17. 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.

  18. 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.

  19. Functional near-infrared spectroscopy (fNIRS) of brain function during active balancing using a video game system.

    PubMed

    Karim, Helmet; Schmidt, Benjamin; Dart, Dwight; Beluk, Nancy; Huppert, Theodore

    2012-03-01

    Functional near-infrared spectroscopy (fNIRS) is a portable, non-invasive, brain imaging technology that uses low levels of non-ionizing light to record changes in cerebral blood flow in the brain through optical sensors placed on the surface of the scalp. These signals are recorded via flexible fiber optic cables, which allow neuroimaging experiments to be conducted on participants while performing tasks such as standing or walking. FNIRS has the potential to provide new insights into the evolution of brain activation during ambulatory motor learning tasks and standing tasks to probe balance and vestibular function. In this study, a 32 channel fNIRS system was used to record blood flow changes in the frontal, motor, sensory, and temporal cortices during active balancing associated with playing a video game simulating downhill skiing (Nintendo Wii™; Wii-fit™). Using fNIRS, we found activation of superior temporal gyrus, which was modulated by the difficulty of the balance task. This region had been previously implicated in vestibular function from other animal and human studies.

  20. Functional Near-infrared Spectroscopy (fNIRS) of Brain Function During Active Balancing Using a Video Game System

    PubMed Central

    Karim, Helmet; Schmidt, Benjamin; Dart, Dwight; Beluk, Nancy; Huppert, Theodore

    2011-01-01

    Functional near-infrared spectroscopy (fNIRS) is a portable, non-invasive, brain imaging technology that uses low levels of non-ionizing light to record changes in cerebral blood flow in the brain through optical sensors placed on the surface of the scalp. These signals are recorded via flexible fiber optic cables, which allow neuroimaging experiments to be conducted on participants while performing tasks such as standing or walking. FNIRS has the potential to provide new insights into the evolution of brain activation during ambulatory motor learning tasks and standing tasks to probe balance and vestibular function. In this study, a 32 channel fNIRS system was used to record blood flow changes in the frontal, motor, sensory, and temporal cortices during active balancing associated with playing a video game simulating downhill skiing (Nintendo Wii™; Wii-fit™). Using fNIRS, we found activation of superior temporal gyrus, which was modulated by the difficulty of the balance task. This region had been previously implicated in vestibular function from other animal and human studies. PMID:22078300

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. 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.

  6. Transcriptional coactivator CIITA, a functional homolog of TAF1, has kinase activity.

    PubMed

    Soe, Katherine C; Devaiah, Ballachanda N; Singer, Dinah S

    2013-11-01

    The Major Histocompatibility Complex (MHC) class II transactivator (CIITA) mediates activated immune responses and its deficiency results in the Type II Bare Lymphocyte Syndrome. CIITA is a transcriptional co-activator that regulates γ-interferon-activated transcription of MHC class I and class II genes. It is also a functional homolog of TAF1, a component of the general transcription factor complex TFIID. TAF1 and CIITA both possess intrinsic acetyltransferase (AT) activity that is required for transcription initiation. In response to induction by γ-interferon, CIITA and it's AT activity bypass the requirement for TAF1 AT activity. TAF1 also has kinase activity that is essential for its function. However, no similar activity has been identified for CIITA thus far. Here we report that CIITA, like TAF1, is a serine-threonine kinase. Its substrate specificity parallels, but does not duplicate, that of TAF1 in phosphorylating the TFIID component TAF7, the RAP74 subunit of the general transcription factor TFIIF and histone H2B. Like TAF1, CIITA autophosphorylates, affecting its interaction with TAF7. Additionally, CIITA phosphorylates histone H2B at Ser36, a target of TAF1 that is required for transcription during cell cycle progression and stress response. However, unlike TAF1, CIITA also phosphorylates all the other histones. The identification of this novel kinase activity of CIITA further clarifies its role as a functional homolog of TAF1 which may operate during stress and γ-IFN activated MHC gene transcription.

  7. 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…

  8. 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...

  9. 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...

  10. 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.…

  11. 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…

  12. Rev-RRE Functional Activity Differs Substantially Among Primary HIV-1 Isolates.

    PubMed

    Jackson, Patrick E; Tebit, Denis M; Rekosh, David; Hammarskjold, Marie-Louise

    2016-09-01

    The HIV-1 replication cycle requires the nucleocytoplasmic export of intron-containing viral RNAs, a process that is ordinarily restricted. HIV overcomes this by means of the viral Rev protein, which binds to an RNA secondary structure called the Rev response element (RRE) present in all unspliced or incompletely spliced viral RNA transcripts. The resulting mRNP complex is exported through interaction with cellular factors. The Rev-RRE binding interaction is increasingly understood to display remarkable structural plasticity, but little is known about how Rev-RRE sequence differences affect functional activity. To study this issue, we utilized a lentiviral vector assay in which vector titer is dependent on the activity of selected Rev-RRE pairs. We found that Rev-RRE functional activity varies significantly (up to 24-fold) between naturally occurring viral isolates. The activity differences of the Rev-RRE cognate pairs track closely with Rev, but not with RRE activity. This variation in Rev activity is not correlated with differences in Rev steady state protein levels. These data suggest that Rev sequence differences drive substantial variation in Rev-RRE functional activity between patients. Such variation may play a role in viral adaptation to different immune milieus within and between patients and may be significant in the establishment of latency. The identification of differences in Rev-RRE functional activity in naturally occurring isolates may also permit more efficient production of lentiviral vectors. PMID:27147495

  13. 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...

  14. [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.

  15. 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. PMID:25708326

  16. 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.

  17. Assessments of Muscle Oxygenation and Cortical Activity Using Functional Near-infrared Spectroscopy in Healthy Adults During Hybrid Activation.

    PubMed

    Lin, Tai-You; Wu, Jin-Shang; Lin, Linda L; Ho, Ting-Chuan; Lin, Pei-Yi; Chen, Jia-Jin J

    2016-01-01

    Hybrid activation (HA), patterned electrical stimulation (ES) superimposed on attempted voluntary movement in close synchrony, can augment muscle force output. It has been proposed for limb function restoration and neuromodulation. Limited studies have been performed to investigate the influences of HA on muscle oxygenation and brain cortical activity. The present study investigates muscle oxygenation and cortical activity during isometric knee extension tasks with voluntary contraction (VOL) only, ES only, and with HA at three stimulation intensities, namely 10 mA (HA-I), 30 mA (HA-II), and 50 mA (HA-III). A frequency-domain near-infrared spectroscopy system was employed to assess the muscle oxygenation in the vastus lateralis as well as the cortical activity from the bilateral sensorimotor cortices (SMCs), premotor cortices (PMCs), and supplementary motor areas (SMAs). Our results show that the increased ES contribution during HA significantly increased O2 demand in working muscle, implying that the intervention of ES accelerates the muscle metabolism during muscle contraction. For cortical activation, ES only had a similar cortical activation pattern to that during VOL but with lower activation in SMCs, PMCs, and SMAs. Augmented sensorimotor activation was observed during the HA-II condition. The enhanced level of cortical activation during HA was not only affected by the ES contribution within HA but also related to the functional specificity of cortical areas. Our results suggest that HA can effectively enhance the muscle oxygen demand as well as the activation of cortical regions, and that the ES contribution within HA is a key factor.

  18. Cardiac-Specific YAP Activation Improves Cardiac Function and Survival in an Experimental Murine MI Model

    PubMed Central

    Lin, Zhiqiang; von Gise, Alexander; Zhou, Pingzhu; Gu, Fei; Ma, Qing; Jiang, Jiangming; Yau, Allan L.; Buck, Jessica N.; Gouin, Katryna A.; van Gorp, Pim R. R.; Zhou, Bin; Chen, Jinghai; Seidman, Jonathan G.; Wang, Da-zhi; Pu, William T.

    2014-01-01

    Rationale Yes-Associated Protein (YAP), the terminal effector of the Hippo signaling pathway, is crucial for regulating embryonic cardiomyocyte (CM) proliferation. Objective We hypothesized that YAP activation after myocardial infarction would preserve cardiac function and improve survival. Methods and Results We used a cardiac-specific, inducible expression system to activate YAP in adult mouse heart. Activation of YAP in adult heart promoted CM proliferation and did not deleteriously affect heart function. Furthermore, YAP activation after myocardial infarction (MI) preserved heart function and reduced infarct size. Using adeno-associated virus subtype 9 (AAV9) as a delivery vector, we expressed human YAP in the adult murine myocardium immediately after MI. We found that AAV9:hYAP significantly improved cardiac function and mouse survival. AAV9:hYAP did not exert its salutary effects by reducing CM apoptosis. Rather, AAV9:hYAP stimulated adult CM proliferation. Gene expression profiling indicated that AAV9:hYAP stimulated expression of cell cycle genes and promoted a less mature cardiac gene expression signature. Conclusions Cardiac specific YAP activation after MI mitigated myocardial injury, improved cardiac function, and enhanced survival. These findings suggest that therapeutic activation of YAP or its downstream targets, potentially through AAV-mediated gene therapy, may be a strategy to improve outcome after MI. PMID:24833660

  19. Physical activity interventions and children's mental function: An introduction and overview

    PubMed Central

    Tomporowski, Phillip D.; Lambourne, Kate; Okumura, Michelle S.

    2011-01-01

    Background This review provides a historical overview of physical activity interventions designed by American educators and an evaluation of research that has assessed the effects of exercise on children's mental function. Method Historical descriptions of the emergence of American physical education doctrine throughout the 20th century were evaluated. Prior reviews of studies that assessed the effects of single acute bouts of exercise and the effects of chronic exercise training on children's mental function were examined and the results of recent studies were summarized. Results Physical activity interventions designed for American children have reflected two competing views: activities should promote physical fitness and activities should promote social, emotional, and intellectual development. Research results indicate that exercise fosters the emergence of children's mental function; particularly executive functioning. The route by which physical activity impacts mental functioning is complex and is likely moderated by several variables, including physical fitness level, health status, and numerous psycho-social factors. Conclusion Physical activity interventions for children should be designed to meet multiple objectives; e.g., optimize physical fitness, promote health-related behaviors that offset obesity, and facilitate mental development. PMID:21420981

  20. Mutational Analysis of Escherichia coli MoeA: Two Functional Activities Map to the Active Site Cleft

    SciTech Connect

    Nichols,J.; Xiang, S.; Schindelin, H.; Rajagopalan, K.

    2007-01-01

    The molybdenum cofactor is ubiquitous in nature, and the pathway for Moco biosynthesis is conserved in all three domains of life. Recent work has helped to illuminate one of the most enigmatic steps in Moco biosynthesis, ligation of metal to molybdopterin (the organic component of the cofactor) to form the active cofactor. In Escherichia coli, the MoeA protein mediates ligation of Mo to molybdopterin while the MogA protein enhances this process in an ATP-dependent manner. The X-ray crystal structures for both proteins have been previously described as well as two essential MogA residues, Asp49 and Asp82. Here we describe a detailed mutational analysis of the MoeA protein. Variants of conserved residues at the putative active site of MoeA were analyzed for a loss of function in two different, previously described assays, one employing moeA{sup -} crude extracts and the other utilizing a defined system. Oddly, no correlation was observed between the activity in the two assays. In fact, our results showed a general trend toward an inverse relationship between the activity in each assay. Moco binding studies indicated a strong correlation between a variant's ability to bind Moco and its activity in the purified component assay. Crystal structures of the functionally characterized MoeA variants revealed no major structural changes, indicating that the functional differences observed are not due to disruption of the protein structure. On the basis of these results, two different functional areas were assigned to regions at or near the MoeA active site cleft.

  1. Does motion-related brain functional connectivity reflect both artifacts and genuine neural activity?

    PubMed

    Pujol, Jesus; Macià, Dídac; Blanco-Hinojo, Laura; Martínez-Vilavella, Gerard; Sunyer, Jordi; de la Torre, Rafael; Caixàs, Assumpta; Martín-Santos, Rocío; Deus, Joan; Harrison, Ben J

    2014-11-01

    Imaging research on functional connectivity is uniquely contributing to characterize the functional organization of the human brain. Functional connectivity measurements, however, may be significantly influenced by head motion that occurs during image acquisition. The identification of how motion influences such measurements is therefore highly relevant to the interpretation of a study's results. We have mapped the effect of head motion on functional connectivity in six different populations representing a wide range of potential influences of motion on functional connectivity. Group-level voxel-wise maps of the correlation between a summary head motion measurement and functional connectivity degree were estimated in 80 young adults, 71 children, 53 older adults, 20 patients with Down syndrome, 24 with Prader-Willi syndrome and 20 with Williams syndrome. In highly compliant young adults, motion correlated with functional connectivity measurements showing a system-specific anatomy involving the sensorimotor cortex, visual areas and default mode network. Further characterization was strongly indicative of these changes expressing genuine neural activity related to motion, as opposed to pure motion artifact. In the populations with larger head motion, results were more indicative of widespread artifacts, but showing notably distinct spatial distribution patterns. Group-level regression of motion effects was efficient in removing both generalized changes and changes putatively related to neural activity. Overall, this study endorses a relatively simple approach for mapping distinct effects of head motion on functional connectivity. Importantly, our findings support the intriguing hypothesis that a component of motion-related changes may reflect system-specific neural activity.

  2. 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.

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... programmatic activity costs? 641.864 Section 641.864 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION... costs of physical examinations, compensation for scheduled work hours during which a host agency is... and selection, intake, orientation, assessment, and preparation and updating of IEPs; (c)...

  4. Solubilization of a functionally active platelet-activating factor receptor from rabbit platelets.

    PubMed Central

    Rogers, J E; Duronio, V; Wong, S I; McNeil, M; Salari, H

    1991-01-01

    Binding of platelet-activating factor (PAF) to a specific high-affinity membrane receptor has been demonstrated in numerous cell types, but very little is known about the molecular nature of this receptor. The receptor from rabbit platelets was solubilized using CHAPS, digitonin, octyl glucoside, Nonidet P-40 or sodium cholate, either with pre-bound [3H]PAF or in the absence of ligand. We have been able to demonstrate for the first time that the receptor solubilized with CHAPS, in the absence of ligand, could retain its binding activity. It migrated as a high molecular mass complex (greater than 350 kDa) on a Bio-Gel A-0.5 m gel filtration column. Binding to solubilized receptor rapidly reached an equilibrium at room temperature, but was much slower at 0 degrees C. Scatchard plots were used to calculate the number (approx. 100 per cell) and the affinity (Kd 2.5 +/- 1.4 nM) of the solubilized receptors. These values were comparable with those obtained from whole-cell binding experiments. Competition by PAF antagonists also verified that the assay was measuring PAF receptor binding activity. The presence of a protein in the receptor complex was demonstrated by heat and trypsin inactivation of binding activity. Trypsin had no effect on binding of PAF to whole cells, but was able to decrease binding activity in solubilized receptor preparations. Attempts to demonstrate the involvement of a glycoprotein by use of various lectin columns proved unsuccessful. The latter results are consistent with findings suggesting that the binding site of the PAF receptor may not be exposed at the cell surface. PMID:1654881

  5. Differential expression of active zone proteins in neuromuscular junctions suggests functional diversification.

    PubMed

    Juranek, Judyta; Mukherjee, Konark; Rickmann, Michael; Martens, Henrik; Calka, Jaroslaw; Südhof, Thomas C; Jahn, Reinhard

    2006-12-01

    Nerve terminals of the central nervous system (CNS) contain specialized release sites for synaptic vesicles, referred to as active zones. They are characterized by electron-dense structures that are tightly associated with the presynaptic plasma membrane and organize vesicle docking and priming sites. Recently, major protein constituents of active zones have been identified, including the proteins Piccolo, Bassoon, RIM, Munc13, ERCs/ELKs/CASTs and liprins. While it is becoming apparent that each of these proteins is essential for synaptic function in the CNS, it is not known to what extent these proteins are involved in synaptic function of the peripheral nervous system. Somatic neuromuscular junctions contain morphologically and functionally defined active zones with similarities to CNS synapses. In contrast, sympathetic neuromuscular varicosities lack active zone-like morphological specializations. Using immunocytochemistry at the light and electron microscopic level we have now performed a systematic investigation of all five major classes of active zone proteins in peripheral neuromuscular junctions. Our results show that somatic neuromuscular endplates contain a full complement of all active zone proteins. In contrast, varicosities of the vas deferens contain a subset of active zone proteins including Bassoon and ELKS2, with the other four components being absent. We conclude that Bassoon and ELKS2 perform independent and specialized functions in synaptic transmission of autonomic synapses.

  6. Using catalytic atom maps to predict the catalytic functions present in enzyme active sites.

    PubMed

    Nosrati, Geoffrey R; Houk, K N

    2012-09-18

    Catalytic atom maps (CAMs) are minimal models of enzyme active sites. The structures in the Protein Data Bank (PDB) were examined to determine if proteins with CAM-like geometries in their active sites all share the same catalytic function. We combined the CAM-based search protocol with a filter based on the weighted contact number (WCN) of the catalytic residues, a measure of the "crowdedness" of the microenvironment around a protein residue. Using this technique, a CAM based on the Ser-His-Asp catalytic triad of trypsin was able to correctly identify catalytic triads in other enzymes within 0.5 Å rmsd of the CAM with 96% accuracy. A CAM based on the Cys-Arg-(Asp/Glu) active site residues from the tyrosine phosphatase active site achieved 89% accuracy in identifying this type of catalytic functionality. Both of these CAMs were able to identify active sites across different fold types. Finally, the PDB was searched to locate proteins with catalytic functionality similar to that present in the active site of orotidine 5'-monophosphate decarboxylase (ODCase), whose mechanism is not known with certainty. A CAM, based on the conserved Lys-Asp-Lys-Asp tetrad in the ODCase active site, was used to search the PDB for enzymes with similar active sites. The ODCase active site has a geometry similar to that of Schiff base-forming Class I aldolases, with lowest aldolase rmsd to the ODCase CAM at 0.48 Å. The similarity between this CAM and the aldolase active site suggests that ODCase has the correct catalytic functionality present in its active site for the generation of a nucleophilic lysine. PMID:22909276

  7. Using Catalytic Atom Maps to Predict the Catalytic Functions Present in Enzyme Active Sites

    PubMed Central

    Nosrati, Geoffrey R.; Houk, K. N.

    2012-01-01

    Catalytic Atom Maps (CAMs) are minimal models of enzyme active sites. The structures in the Protein Data Bank (PDB) were examined to determine if proteins with CAM-like geometries in their active sites all share the same catalytic function. We combined the CAM-based search protocol with a filter based on the weighted contact number (WCN) of the catalytic residues, a measure of the “crowdedness” of the microenvironment around a protein residue. Using this technique, a CAM based on the Ser-His-Asp catalytic triad of trypsin was able to correctly identify catalytic triads in other enzymes within 0.5 Å RMSD of the Catalytic Atom Map with 96% accuracy. A CAM based on the Cys-Arg-(Asp/Glu) active site residues from the tyrosine phosphatase active site achieved 89% accuracy in identifying this type of catalytic functionality. Both of these Catalytic Atom Maps were able to identify active sites across different fold types. Finally, the PDB was searched to locate proteins with catalytic functionality similar to that present in the active site of orotidine 5′-monophosphate decarboxylase (ODCase), whose mechanism is not known with certainty. A CAM, based on the conserved Lys-Asp-Lys-Asp tetrad in the ODCase active site, was used to search the PDB for enzymes with similar active sites. The ODCase active site has a geometry similar to that of Schiff base-forming Class I aldolases, with lowest aldolase RMSD to the ODCase CAM at 0.48 Å. The similarity between this CAM and the aldolase active site suggests that ODCase has the correct catalytic functionality present in its active site for the generation of a nucleophilic lysine. PMID:22909276

  8. Physical activity and memory functions: are neurotrophins and cerebral gray matter volume the missing link?

    PubMed

    Flöel, A; Ruscheweyh, R; Krüger, K; Willemer, C; Winter, B; Völker, K; Lohmann, H; Zitzmann, M; Mooren, F; Breitenstein, C; Knecht, S

    2010-02-01

    Epidemiological studies reveal better cognitive function in physically active individuals. Possible mediators for this effect are neurotrophins, which are up-regulated through physical exercise and induce neuronal growth and synaptogenesis in the animal model. Here we cross-sectionally assessed 75 healthy older individuals for levels of physical activity, aerobic fitness, and memory encoding, as well as neurotrophin levels and cerebral gray matter volume. We found that physical activity, but not cardiovascular fitness, was associated with better memory encoding after controlling for age, sex, education, depression, alcohol consumption, and smoking. Higher levels of physical activity were associated with higher levels of the neurotrophin granulocyte colony stimulating factor (G-CSF) and increased cerebral gray matter volume in prefrontal and cingulate cortex as assessed by magnetic resonance voxel-based morphometry. While mediating factors will need to be further elucidated, these findings indicate that even low-level physical activity exerts beneficial effects on memory functions in older individuals.

  9. Application of activity-based protein profiling to study enzyme function in adipocytes.

    PubMed

    Galmozzi, Andrea; Dominguez, Eduardo; Cravatt, Benjamin F; Saez, Enrique

    2014-01-01

    Activity-based protein profiling (ABPP) is a chemical proteomics approach that utilizes small-molecule probes to determine the functional state of enzymes directly in native systems. ABPP probes selectively label active enzymes, but not their inactive forms, facilitating the characterization of changes in enzyme activity that occur without alterations in protein levels. ABPP can be a tool superior to conventional gene expression and proteomic profiling methods to discover new enzymes active in adipocytes and to detect differences in the activity of characterized enzymes that may be associated with disorders of adipose tissue function. ABPP probes have been developed that react selectively with most members of specific enzyme classes. Here, using as an example the serine hydrolase family that includes many enzymes with critical roles in adipocyte physiology, we describe methods to apply ABPP analysis to the study of adipocyte enzymatic pathways.

  10. Structural basis of the cofactor function of denatured albumin in plasminogen activation by tissue-type plasminogen activator.

    PubMed

    Galántai, Rita; Módos, Károly; Fidy, Judit; Kolev, Krasimir; Machovich, Raymund

    2006-03-17

    Certain denatured proteins function as cofactors in the activation of plasminogen by tissue-type plasminogen activator. The present study approached the structural requirements for the cofactor activity of a model protein (human serum albumin). Heat denaturation of 100-230 microM albumin (80 degrees C and 60-90 min) reproducibly yielded aggregates with radius in the range of 10-150 nm. The major determinant of the cofactor potency was the size of the aggregates. The increase of particle size correlated with the cofactor activity, and there was a minimal requirement for the size of the cofactor (about 10 nm radius). Similar to other proteins, the molecular aggregates with cofactor function contained a significant amount of antiparallel intermolecular beta-sheets. Plasmin pre-digestion increased the cofactor efficiency (related to C-terminal lysine exposure) and did not affect profoundly the structure of the aggregates, suggesting a long-lasting and even a self-augmenting cofactor function of the denatured protein. PMID:16438933

  11. Developmental changes in motor cortex activity as infants develop functional motor skills.

    PubMed

    Nishiyori, Ryota; Bisconti, Silvia; Meehan, Sean K; Ulrich, Beverly D

    2016-09-01

    Despite extensive research examining overt behavioral changes of motor skills in infants, the neural basis underlying the emergence of functional motor control has yet to be determined. We used functional near-infrared spectroscopy (fNIRS) to record hemodynamic activity of the primary motor cortex (M1) from 22 infants (11 six month-olds, 11 twelve month-olds) as they reached for an object, and stepped while supported over a treadmill. Based on the developmental systems framework, we hypothesized that as infants increased goal-directed experience, neural activity shifts from a diffused to focal pattern. Results showed that for reaching, younger infants showed diffuse areas of M1 activity that became focused by 12 months. For elicited stepping, younger infants produced much less M1 activity which shifted to diffuse activity by 12 months. Thus, the data suggest that as infants gain goal-directed experience, M1 activity emerges, initially showing a diffuse area of activity, becoming refined as the behavior stabilizes. Our data begin to document the cortical activity underlying early functional skill acquisition.

  12. Continuous monitoring of functional activities using wearable, wireless gyroscope and accelerometer technology.

    PubMed

    Wagenaar, Robert C; Sapir, Inbal; Zhang, Yuting; Markovic, Stacey; Vaina, Lucia M; Little, Thomas D C

    2011-01-01

    The development of functional activity monitors (FAMs) will allow rehabilitation researchers and clinicians to evaluate treatment efficacy, to monitor compliance to exercise instructions, and to provide real time feedback in the treatment of movement disorders during the performance of daily activities. The purpose of the present study was to develop and test a small sized wearable FAM system comprised of three sensors positioned on the sternum and both thighs, wireless Bluetooth transmission capability to a smartphone, and computationally efficient activity detection algorithms for the accurate detection of functional activities. Each sensor was composed of a tri-axial accelerometer and a tri-axial gyroscope. Computationally efficient activity recognition algorithms were developed, using a sliding window of 1 second, the variability of the tilt angle time series and power spectral analysis. In addition, it includes a decision tree that identifies postures such as sitting, standing and lying, walking at comfortable, slow and fast speeds, transitions between these functional activities (e.g, sit-to-stand and stand-to-sit), activity duration and step frequency. In a research lab setting the output of the FAM system, video recordings and a 3D motion analysis system were compared in 10 healthy young adults. The results show that the agreement between the FAM system and the video recordings ranged from 98.10% to 100% for all postures, transfers and walking periods. There were no significant differences in activity durations and step frequency between measurement instruments. PMID:22255423

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

    PubMed

    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

  14. Relationship Between Cortical Thickness and Functional Activation in the Early Blind

    PubMed Central

    Anurova, Irina; Renier, Laurent A.; De Volder, Anne G.; Carlson, Synnöve; Rauschecker, Josef P.

    2015-01-01

    Early blindness results in both structural and functional changes of the brain. However, these changes have rarely been studied in relation to each other. We measured alterations in cortical thickness (CT) caused by early visual deprivation and their relationship with cortical activity. Structural and functional magnetic resonance imaging was performed in 12 early blind (EB) humans and 12 sighted controls (SC). Experimental conditions included one-back tasks for auditory localization and pitch identification, and a simple sound-detection task. Structural and functional data were analyzed in a whole-brain approach and within anatomically defined regions of interest in sensory areas of the spared (auditory) and deprived (visual) modalities. Functional activation during sound-localization or pitch-identification tasks correlated negatively with CT in occipital areas of EB (calcarine sulcus, lingual gyrus, superior and middle occipital gyri, and cuneus) and in nonprimary auditory areas of SC. These results suggest a link between CT and activation and demonstrate that the relationship between cortical structure and function may depend on early sensory experience, probably via selective pruning of exuberant connections. Activity-dependent effects of early sensory deprivation and long-term practice are superimposed on normal maturation and aging. Together these processes shape the relationship between brain structure and function over the lifespan. PMID:24518755

  15. 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

  16. Some problems for representations of brain organization based on activation in functional imaging.

    PubMed

    Sidtis, John J

    2007-08-01

    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 brain damage. However, the enthusiastic onslaught of brain images, frequently presented as veridical representations of mental function, has sometimes overwhelmed some basic facts about brain organization repeatedly observed over more than a century. In particular, the lateralization of speech and language to the left cerebral hemisphere in over 90% of the right-handed population does not appear to have been taken as a serious constraint in the interpretation of imaging results in studies of these functions. This paper reviews a number of areas in which standard activation assumptions yield results that are at odds with clinical experience. The activation approach will be contrasted with a performance-based analysis of functional image data, which, at least in the case of speech production, yields results in better agreement with lesion data. Functional imaging represents enormous opportunities for understanding brain-behavior relationships, but at the present level of understanding of what is being represented in such images, it is premature to adhere to a single approach based on the strong but questionable assumptions inherent in most activation studies. PMID:16938343

  17. Physical Activity and Cognitive Function in Older Adults: The Mediating Effect of Depressive Symptoms.

    PubMed

    Vance, David E; Marson, Daniel C; Triebel, Kristen L; Ball, Karlene K; Wadley, Virginia G; Cody, Shameka L

    2016-01-01

    Depressive symptoms and social networks may influence the relationship between physical activity and cognition. Using structural equation modeling, depressive symptoms and social networks were examined as mediators between physical activity and cognition in community-dwelling older adults (N = 122), with a range of cognitive abilities (e.g., normal, mild cognitive impairment). The model included age, physical activity, sedentary behavior, sleeping, social networks, depressive symptoms, and cognitive function. A path was observed between physical activity, depressive symptoms, and cognition; specifically, those who were more physically active experienced less depression and better cognitive functioning. No relationship between social networks and cognition was found. This model fits the data well (goodness-of-fit index = .93, adjusted goodness-of-fit index = .90, root mean square error of approximation = .06). Results suggest that physical activity may mitigate depressive symptoms, with beneficial effects on cognitive functioning in both those with and without mild cognitive impairment. Suggestions for managing depression and improving cognitive functioning are provided. PMID:27224681

  18. Decreased fibrinolytic activity and increased platelet function in hypertension. Possible influence of calcium antagonism.

    PubMed

    Gleerup, G; Winther, K

    1991-02-01

    Twelve patients with mild hypertension were compared, after 14 days of placebo, with an age- and gender-matched group of 12 healthy volunteers for platelet aggregability and fibrinolytic activity. Following this, 10 of the 12 hypertensives were treated with the calcium antagonist isradipine for 12 months. Blood was drawn for determinations of platelet aggregation and fibrinolytic activity after two weeks and 12 months of treatment. Platelet aggregation tended to increase in the hypertensives compared with controls, indicated by a lowering of the adenosine diphosphate (ADP) threshold value for irreversible aggregation. Tissue-plasminogen activator (t-PA) activity was significantly decreased in hypertensives compared to controls (P less than .05). During therapy, platelet aggregation decreased and t-PA activity increased (P less than .05). The present data suggest that fibrinolytic activity is decreased and platelet aggregation increased in mild hypertension. Besides the blood pressure-lowering effect, isradipine may protect against thromboembolic diseases by modifying platelet function and fibrinolytic activity.

  19. 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. PMID:24970234

  20. 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.

  1. Nucleosome distortion as a possible mechanism of transcription activation domain function.

    PubMed

    Erkina, Tamara Y; Erkine, Alexandre M

    2016-01-01

    After more than three decades since the discovery of transcription activation domains (ADs) in gene-specific activators, the mechanism of their function remains enigmatic. The widely accepted model of direct recruitment by ADs of co-activators and basal transcriptional machinery components, however, is not always compatible with the short size yet very high degree of sequence randomness and intrinsic structural disorder of natural and synthetic ADs. In this review, we formulate the basis for an alternative and complementary model, whereby sequence randomness and intrinsic structural disorder of ADs are necessary for transient distorting interactions with promoter nucleosomes, triggering promoter nucleosome translocation and subsequently gene activation. PMID:27679670

  2. Neuroelectrical decomposition of spontaneous brain activity measured with functional magnetic resonance imaging.

    PubMed

    Liu, Zhongming; de Zwart, Jacco A; Chang, Catie; Duan, Qi; van Gelderen, Peter; Duyn, Jeff H

    2014-11-01

    Spontaneous activity in the human brain occurs in complex spatiotemporal patterns that may reflect functionally specialized neural networks. Here, we propose a subspace analysis method to elucidate large-scale networks by the joint analysis of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data. The new approach is based on the notion that the neuroelectrical activity underlying the fMRI signal may have EEG spectral features that report on regional neuronal dynamics and interregional interactions. Applying this approach to resting healthy adults, we indeed found characteristic spectral signatures in the EEG correlates of spontaneous fMRI signals at individual brain regions as well as the temporal synchronization among widely distributed regions. These spectral signatures not only allowed us to parcel the brain into clusters that resembled the brain's established functional subdivision, but also offered important clues for disentangling the involvement of individual regions in fMRI network activity.

  3. 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

  4. Dysfunctional Activation of the Cerebellum in Schizophrenia: A Functional Neuroimaging Meta-Analysis

    PubMed Central

    Bernard, Jessica A.; Mittal, Vijay A.

    2014-01-01

    The cognitive dysmetria framework postulates that the deficits seen in schizophrenia are due to underlying cerebello-thalamo-cortical dysfunction. The cerebellum is thought to be crucial in the formation of internal models for both motor and cognitive behaviors. In healthy individuals there is a functional topography within the cerebellum. Alterations in the functional topography and activation of the cerebellum in schizophrenia patients may be indicative of altered internal models, providing support for this framework. Using state-of-the-art neuroimaging meta-analysis, we investigated cerebellar activation across a variety of task domains affected in schizophrenia and in comparison to healthy controls. Our results indicate an altered functional topography in patients. This was especially apparent for emotion and working memory tasks, and may be related to deficits in these domains. Results suggest that an altered cerebellar functional topography in schizophrenia may be contributing to the many deficits associated with the disease, perhaps due to dysfunctional internal models. PMID:26392921

  5. Functional Based Adaptive and Fuzzy Sliding Controller for Non-Autonomous Active Suspension System

    NASA Astrophysics Data System (ADS)

    Huang, Shiuh-Jer; Chen, Hung-Yi

    In this paper, an adaptive sliding controller is developed for controlling a vehicle active suspension system. The functional approximation technique is employed to substitute the unknown non-autonomous functions of the suspension system and release the model-based requirement of sliding mode control algorithm. In order to improve the control performance and reduce the implementation problem, a fuzzy strategy with online learning ability is added to compensate the functional approximation error. The update laws of the functional approximation coefficients and the fuzzy tuning parameters are derived from the Lyapunov theorem to guarantee the system stability. The proposed controller is implemented on a quarter-car hydraulic actuating active suspension system test-rig. The experimental results show that the proposed controller suppresses the oscillation amplitude of the suspension system effectively.

  6. Amygdala activity can be modulated by unexpected chord functions during music listening.

    PubMed

    Koelsch, Stefan; Fritz, Thomas; Schlaug, Gottfried

    2008-12-01

    Numerous earlier studies have investigated the cognitive processing of musical syntax with regular and irregular chord sequences. However, irregular sequences may also be perceived as unexpected, and therefore have a different emotional valence than regular sequences. We provide behavioral data showing that irregular chord functions presented in chord sequence paradigms are perceived as less pleasant than regular sequences. A reanalysis of functional MRI data showed increased blood oxygen level-dependent signal changes bilaterally in the amygdala in response to music-syntactically irregular (compared with regular) chord functions. The combined data indicate that music-syntactically irregular events elicit brain activity related to emotional processes, and that, in addition to intensely pleasurable music or highly unpleasant music, single chord functions can also modulate amygdala activity.

  7. Lifelong physical activity preserves functional sympatholysis and purinergic signalling in the ageing human leg.

    PubMed

    Mortensen, S P; Nyberg, M; Winding, K; Saltin, B

    2012-12-01

    Ageing is associated with an impaired ability to modulate sympathetic vasoconstrictor activity (functional sympatholysis) and a reduced exercise hyperaemia. The purpose of this study was to investigate whether a physically active lifestyle can offset the impaired functional sympatholysis and exercise hyperaemia in the leg and whether ATP signalling is altered by ageing and physical activity. Leg haemodynamics, interstitial [ATP] and P2Y(2) receptor content was determined in eight young (23 ± 1 years), eight lifelong sedentary elderly (66 ± 2 years) and eight lifelong active elderly (62 ± 2 years) men at rest and during one-legged knee extensions (12 W and 45% maximal workload (WL(max))) and arterial infusion of ACh and ATP with and without tyramine. The vasodilatory response to ACh was lowest in the sedentary elderly, higher in active elderly (P < 0.05) and highest in the young men (P < 0.05), whereas ATP-induced vasodilatation was lower in the sedentary elderly (P < 0.05). During exercise (12 W), leg blood flow, vascular conductance and VO2 was lower and leg lactate release higher in the sedentary elderly compared to the young (P < 0.05), whereas there was no difference between the active elderly and young. Interstitial [ATP] during exercise and P2Y(2) receptor content were higher in the active elderly compared to the sedentary elderly (P < 0.05). Tyramine infusion lowered resting vascular conductance in all groups, but only in the sedentary elderly during exercise (P < 0.05). Tyramine did not alter the vasodilator response to ATP infusion in any of the three groups. Plasma [noradrenaline] increased more during tyramine infusion in both elderly groups compared to young (P < 0.05). A lifelong physically active lifestyle can maintain an intact functional sympatholysis during exercise and vasodilator response to ATP despite a reduction in endothelial nitric oxide function. A physically active lifestyle increases interstitial ATP levels and skeletal muscle P2Y(2

  8. Lifelong physical activity preserves functional sympatholysis and purinergic signalling in the ageing human leg

    PubMed Central

    Mortensen, S P; Nyberg, M; Winding, K; Saltin, B

    2012-01-01

    Ageing is associated with an impaired ability to modulate sympathetic vasoconstrictor activity (functional sympatholysis) and a reduced exercise hyperaemia. The purpose of this study was to investigate whether a physically active lifestyle can offset the impaired functional sympatholysis and exercise hyperaemia in the leg and whether ATP signalling is altered by ageing and physical activity. Leg haemodynamics, interstitial [ATP] and P2Y2 receptor content was determined in eight young (23 ± 1 years), eight lifelong sedentary elderly (66 ± 2 years) and eight lifelong active elderly (62 ± 2 years) men at rest and during one-legged knee extensions (12 W and 45% maximal workload (WLmax)) and arterial infusion of ACh and ATP with and without tyramine. The vasodilatory response to ACh was lowest in the sedentary elderly, higher in active elderly (P < 0.05) and highest in the young men (P < 0.05), whereas ATP-induced vasodilatation was lower in the sedentary elderly (P < 0.05). During exercise (12 W), leg blood flow, vascular conductance and was lower and leg lactate release higher in the sedentary elderly compared to the young (P < 0.05), whereas there was no difference between the active elderly and young. Interstitial [ATP] during exercise and P2Y2 receptor content were higher in the active elderly compared to the sedentary elderly (P < 0.05). Tyramine infusion lowered resting vascular conductance in all groups, but only in the sedentary elderly during exercise (P < 0.05). Tyramine did not alter the vasodilator response to ATP infusion in any of the three groups. Plasma [noradrenaline] increased more during tyramine infusion in both elderly groups compared to young (P < 0.05). A lifelong physically active lifestyle can maintain an intact functional sympatholysis during exercise and vasodilator response to ATP despite a reduction in endothelial nitric oxide function. A physically active lifestyle increases interstitial ATP levels and skeletal muscle P2Y2 receptor

  9. Family Functioning: Associations with Weight Status, Eating Behaviors, and Physical Activity in Adolescents

    PubMed Central

    Berge, Jerica M.; Wall, Melanie; Larson, Nicole; Loth, Katie A.; Neumark-Sztainer, Dianne

    2012-01-01

    Purpose This paper examines the relationship between family functioning (e.g. communication, closeness, problem solving, behavioral control) and adolescent weight status and relevant eating and physical activity behaviors. Methods Data are from EAT 2010 (Eating and Activity in Teens), a population-based study that assessed eating and activity among socioeconomically and racially/ethnically diverse youth (n = 2,793). Adolescents (46.8% boys, 53.2% girls) completed anthropometric assessments and surveys at school in 2009–2010. Multiple linear regression was used to test the relationship between family functioning and adolescent weight, dietary intake, family meal patterns, and physical activity. Additional regression models were fit to test for interactions by race/ethnicity. Results For adolescent girls, higher family functioning was associated with lower body mass index z-score and percent overweight, less sedentary behavior, higher intake of fruits and vegetables, and more frequent family meals and breakfast consumption. For adolescent boys, higher family functioning was associated with more physical activity, less sedentary behavior, less fast food consumption, and more frequent family meals and breakfast consumption. There was one significant interaction by race/ethnicity for family meals; the association between higher family functioning and more frequent family meals was stronger for non-white boys compared to white boys. Overall, strengths of associations tended to be small with effect sizes ranging from - 0.07 to 0.31 for statistically significant associations. Conclusions Findings suggest that family functioning may be protective for adolescent weight and weight-related health behaviors across all race/ethnicities, although assumptions regarding family functioning in the homes of overweight children should be avoided given small effect sizes. PMID:23299010

  10. 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. PMID:27481946

  11. Physical activity and cognitive function in individuals over 60 years of age: a systematic review

    PubMed Central

    Carvalho, Ashley; Rea, Irene Maeve; Parimon, Tanyalak; Cusack, Barry J

    2014-01-01

    Background It is unclear whether physical activity in later life is beneficial for maintenance of cognitive function. We performed a systematic review examining the effects of exercise on cognitive function in older individuals, and present possible mechanisms whereby physical activity may improve cognition. Methods Sources consisted of PubMed, Medline, CINAHL, the Cochrane Controlled Trials Register, and the University of Washington, School of Medicine Library Database, with a search conducted on August 15, 2012 for publications limited to the English language starting January 1, 2000. Randomized controlled trials including at least 30 participants and lasting at least 6 months, and all observational studies including a minimum of 100 participants for one year, were evaluated. All subjects included were at least 60 years of age. Results Twenty-seven studies met the inclusion criteria. Twenty-six studies reported a positive correlation between physical activity and maintenance or enhancement of cognitive function. Five studies reported a dose-response relationship between physical activity and cognition. One study showed a nonsignificant correlation. Conclusion The preponderance of evidence suggests that physical activity is beneficial for cognitive function in the elderly. However, the majority of the evidence is of medium quality with a moderate risk of bias. Larger randomized controlled trials are needed to clarify the association between exercise and cognitive function and to determine which types of exercise have the greatest benefit on specific cognitive domains. Despite these caveats, the current evidence suggests that physical activity may help to improve cognitive function and, consequently, delay the progression of cognitive impairment in the elderly. PMID:24748784

  12. Scapular Muscle-Activation Ratios in Patients With Shoulder Injuries During Functional Shoulder Exercises

    PubMed Central

    Moeller, Chad R.; Bliven, Kellie C. Huxel; Valier, Alison R. Snyder

    2014-01-01

    Context: Alterations in scapular muscle activation, which are common with glenohumeral (GH) injuries, affect stability and function. Rehabilitation aims to reestablish activation between muscles for stability by progressing to whole-body movements. Objective: To determine scapular muscle-activation ratios and individual muscle activity (upper trapezius [UT], middle trapezius [MT], lower trapezius [LT], serratus anterior [SA]) differences between participants with GH injuries and healthy control participants during functional rehabilitation exercises. Design: Cross-sectional study. Setting: Laboratory. Patients or Other Participants: Thirty-nine participants who had GH injuries (n = 20; age = 23.6 ± 3.2 years, height = 170.7 ± 11.5 cm, mass = 74.7 ± 13.1 kg) or were healthy (n = 19; age = 24.4 ± 3.3 years, height = 173.6 ± 8.6 cm, mass = 74.7 ± 14.8 kg) were tested. Intervention(s): Clinical examination confirmed each participant's classification as GH injury or healthy control. Participants performed 4 exercises (bow and arrow, external rotation with scapular squeeze, lawnmower, robbery) over 3 seconds with no load while muscle activity was recorded. Main Outcome Measure(s): We used surface electromyography to measure UT, MT, LT, and SA muscle activity. Scapular muscle-activation ratios (UT:MT, UT:LT, and UT:SA) were calculated (normalized mean electromyography of the UT divided by normalized mean electromyography of the MT, LT, and SA). Exercise × group analyses of variance with repeated measures were conducted. Results: No group differences for activation ratios or individual muscle activation amplitude were found (P > .05). Similar UT:MT and UT:LT activation ratios during bow-and-arrow and robbery exercises were seen (P > .05); both had greater activation than external-rotation-with-scapular-squeeze and lawnmower exercises (P < .05). The bow-and-arrow exercise elicited the highest activation from the UT, MT, and LT muscles; SA activation was greatest

  13. 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.

  14. 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. PMID:27483541

  15. 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.

  16. [Monocyte functional activity and nonspecific antiviral cellular resistance in adaptation to the conditions of eastern Siberia].

    PubMed

    Zhiburt, E B; Filev, L V; Boĭchak, M P; Volchek, I V; Iakovlev, G P

    1993-01-01

    Monocyte functional activity and antiviral cellular resistance were studied in the newcomers to the Baikal region from the European Russia. A total of 105 patients with acute respiratory diseases and 30 normal subjects were examined. 46 healthy residents of St. Petersburg made up the reference group. The process of adaptation was found to be associated with changes in the functional activity of the immunocompetent cells. The authors came to a conclusion on the principal role of viral injury of the monocytes in the development of acute bronchitis or pneumonia.

  17. Identifying Functional Co-activation Patterns in Neuroimaging Studies via Poisson Graphical Models

    PubMed Central

    Xue, Wenqiong; Kang, Jian; Bowman, F. DuBois; Wager, Tor D.; Guo, Jian

    2014-01-01

    Summary Studying the interactions between different brain regions is essential to achieve a more complete understanding of brain function. In this paper, we focus on identifying functional co-activation patterns and undirected functional networks in neuroimaging studies. We build a functional brain network, using a sparse covariance matrix, with elements representing associations between region-level peak activations. We adopt a penalized likelihood approach to impose sparsity on the covariance matrix based on an extended multivariate Poisson model. We obtain penalized maximum likelihood estimates via the expectation-maximization (EM) algorithm and optimize an associated tuning parameter by maximizing the predictive log-likelihood. Permutation tests on the brain co-activation patterns provide region pair and network-level inference. Simulations suggest that the proposed approach has minimal biases and provides a coverage rate close to 95% of covariance estimations. Conducting a meta-analysis of 162 functional neuroimaging studies on emotions, our model identifies a functional network that consists of connected regions within the basal ganglia, limbic system, and other emotion-related brain regions. We characterize this network through statistical inference on region-pair connections as well as by graph measures. PMID:25147001

  18. Altered Intrinsic Regional Activity and Interregional Functional Connectivity in Post-stroke Aphasia

    PubMed Central

    Yang, Mi; Li, Jiao; Li, Yibo; Li, Rong; Pang, Yajing; Yao, Dezhong; Liao, Wei; Chen, Huafu

    2016-01-01

    Several neuroimaging studies have examined cerebral function in patients who suffer from aphasia, but the mechanism underlying this disorder remains poorly understood. In this study, we examined alterations in the local regional and remote interregional network cerebral functions in aphasia combined with amplitude of low-frequency fluctuations and interregional functional connectivity (FC) using resting-state functional magnetic resonance imaging. A total of 17 post-stroke aphasic patients, all having suffered a stroke in the left hemisphere, as well as 20 age- and sex-matched healthy controls, were enrolled in this study. The aphasic patients showed significantly increased intrinsic regional activity mainly in the contralesional mesial temporal (hippocampus/parahippocampus, [HIP/ParaHIP]) and lateral temporal cortices. In addition, intrinsic regional activity in the contralesional HIP/ParaHIP was negatively correlated with construction score. Aphasic patients showed increased remote interregional FC between the contralesional HIP/ParaHIP and fusiform gyrus, but reduced FC in the ipsilesional occipital and parietal cortices. These findings suggested that the intrinsic regional brain dysfunctions in aphasia were related to interregional functional connectivity. Changes in the intrinsic regional brain activity and associated remote functional connectivity pattern would provide valuable information to enhance the understanding of the pathophysiological mechanisms of aphasia. PMID:27091494

  19. 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

  20. Dissociation of the functional relevance of different pre-stimulus oscillatory activity for memory formation.

    PubMed

    Salari, Neda; Rose, Michael

    2016-01-15

    The state of a neural assembly preceding an incoming stimulus modulates the processing of that subsequently presented stimuli. For human memory formation, the role of oscillatory brain activity within different frequency ranges has been discussed but a more functional relation could not be established. In the present Experiment I, an increase of pre-stimulus theta- (3-7Hz) and beta- (13-17Hz) band oscillations during encoding for later remembered stimuli was observed. To establish a more direct functional relation, we adopted a novel brain-computer-interface (BCI) method to selectively detect oscillatory activity in real-time combined with an adaptive stimulus presentation at different levels of activity. Therefore, in the second experiment the BCI was used to present the visual stimuli with a high temporal resolution directly within defined brain states of beta- or theta-band activity. The quality of the subsequent processing of the stimuli was assessed at the behavioral level with a surprise recognition task. Results revealed a variation of memory performance in direct relation to the amount of pre-stimulus beta- but not theta-band oscillations, suggesting a functional relevance of beta-band oscillations for memory encoding. Thus, the BCI method enabled a more functional differentiation of the effective role of ongoing oscillatory activity.

  1. Dissociation of the functional relevance of different pre-stimulus oscillatory activity for memory formation.

    PubMed

    Salari, Neda; Rose, Michael

    2016-01-15

    The state of a neural assembly preceding an incoming stimulus modulates the processing of that subsequently presented stimuli. For human memory formation, the role of oscillatory brain activity within different frequency ranges has been discussed but a more functional relation could not be established. In the present Experiment I, an increase of pre-stimulus theta- (3-7Hz) and beta- (13-17Hz) band oscillations during encoding for later remembered stimuli was observed. To establish a more direct functional relation, we adopted a novel brain-computer-interface (BCI) method to selectively detect oscillatory activity in real-time combined with an adaptive stimulus presentation at different levels of activity. Therefore, in the second experiment the BCI was used to present the visual stimuli with a high temporal resolution directly within defined brain states of beta- or theta-band activity. The quality of the subsequent processing of the stimuli was assessed at the behavioral level with a surprise recognition task. Results revealed a variation of memory performance in direct relation to the amount of pre-stimulus beta- but not theta-band oscillations, suggesting a functional relevance of beta-band oscillations for memory encoding. Thus, the BCI method enabled a more functional differentiation of the effective role of ongoing oscillatory activity. PMID:26484828

  2. 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. PMID:25677567

  3. 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

  4. ENaC activity requires CFTR channel function independently of phosphorylation in sweat duct.

    PubMed

    Reddy, M M; Quinton, P M

    2005-09-01

    We previously showed that activation of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) Cl- conductance (gCFTR) supports parallel activation of amiloride-sensitive epithelial Na+ channel (ENaC) in the native human sweat duct. However, it is not clear whether phosphorylated CFTR, phosphorylated ENaC, or only Cl(-) -channel function is required for activation. We used basilaterally alpha-toxin-permeabilized human sweat ducts to test the hypothesis that ENaC activation depends only on Cl(-) -channel function and not on phosphorylation of either CFTR or ENaC. CFTR is classically activated by PKA plus millimolar ATP, but cytosolic glutamate activation of gCFTR is independent of ATP and phosphorylation. We show here that both phosphorylation-dependent (PKA) and phosphorylation-independent (glutamate) activation of CFTR Cl- channel function support gENaC activation. We tested whether cytosolic application of 5 mM ATP alone, phosphorylation by cAMP, cGMP, G-protein dependent kinases (all in the presence of 100 microM ATP), or glutamate could support ENaC activation in the absence of gCFTR. We found that none of these agonists activated gENaC by themselves when Cl- current (I(Cl-)) through CFTR was blocked by: 1) Cl- removal, 2) DIDS inhibition, 3) lowering the ATP concentration to 100 microM (instead of 5 mM required to support CFTR channel function), or 4) mutant CFTR (homozygous DeltaF508 CF ducts). However, Cl- gradients in the direction of absorption supported, while Cl- gradients in the direction of secretion prevented ENaC activation. We conclude that the interaction between CFTR and ENaC is dependent on activated I(Cl-) through CFTR in the direction of absorption (Cl- gradient from lumen to cell). But such activation of ENaC is independent of phosphorylation and ATP. However, reversing I(Cl-) through CFTR in the direction of secretion (Cl- gradient from cell to lumen) prevents ENaC activation even in the presence of I(Cl-) through CFTR. PMID

  5. 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

  6. 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

  7. 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

    2016-01-01

    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

  8. Protumorigenic Activity of Plasminogen Activator Inhibitor-1 Through an Antiapoptotic Function

    PubMed Central

    2012-01-01

    Background Plasminogen activator inhibitor-1 (PAI-1) is a protease inhibitor but is paradoxically associated with poor outcomes in cancer patients. However, the mechanisms of its effects on tumor cells have not been explored. Methods Endogenous PAI-1 in human tumor cell lines (HT-1080, A549, HCT-116, and MDA-MB-231) was suppressed by small interfering RNAs (siRNAs) and PAI-039, a small molecule inhibitor of PAI-1, and the effects on apoptosis were examined. Tumorigenicity of PAI-1 knockdown (KD) tumor cells was examined in immunodeficient PAI-1 wild-type and knockout (KO) mice (9–15 per group), and event-free survival was analyzed by the Kaplan–Meier method. The effect of PAI-1 suppression on HT-1080 xenotransplanted tumors was evaluated for cell proliferation, apoptosis, and angiogenesis. All statistical tests were two-sided. Results Genetic and pharmacological inhibition of PAI-1 in the four tumor cell lines increased spontaneous apoptosis (mean fold increase relative to control: HT-1080, siRNA#1, mean = 4.0, 95% CI = 2.6 to 5.3, P < .001; siRNA#2, mean = 2.6, 95% CI = 2.4 to 2.9, P < .001, Student t test), which was blocked in the presence of recombinant PAI-1, a caspase-8 inhibitor, or Fas/FasL neutralizing antibodies and was partially attenuated by a plasmin inhibitor-aprotinin. PAI-1 KO mice implanted with PAI-1 KD HT-1080 cells had decreased tumorigenesis and prolonged survival compared with control mice (P = .002, log-rank test), and their tumors exhibited decreased cell proliferation and angiogenesis and increased apoptosis. Furthermore, five of 15 PAI-1 KO mice implanted with PAI-1 KD HT-1080 cells never developed tumors. Conclusions These data suggest that PAI-1 exerts a protective effect against tumor cell apoptosis by a mechanism that, in part, involves plasmin activation and inhibition of Fas/Fas-L-mediated apoptosis and may be a promising therapeutic target. PMID:22984202

  9. 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

  10. Executive function moderates the intention-behavior link for physical activity and dietary behavior.

    PubMed

    Hall, Peter A; Fong, Geoffrey T; Epp, Lynette J; Elias, Lorin J

    2008-01-01

    Dominant theories of health behavior posit that social-cognitive and conative variables are sufficient to explain health behavior tendencies. The current studies challenge this assumption in two ways: (1) by demonstrating that unique variance in health protective behavior is predictable by knowing about individual differences in executive functioning, and (2) by demonstrating that executive function moderates the association between intention and behavior. In Studies 1 and 2, participants completed a computer-based task of executive function (Go/NoGo task) and articulated 1-week behavioral intentions for physical activity (Study 1) and dietary behavior (Study 2). Hierarchical regression analyses revealed that executive function predicts unique variance in both behaviors, and strongly moderates the association between behavioral intention and behavioral performance. Together behavioral intention and executive function explain more variance in health protective behavior than 'rational actor' models that have been widely adopted and disseminated. PMID:25160480

  11. 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.

  12. Functional organization of the Bel-1 trans activator of human foamy virus.

    PubMed Central

    He, F; Sun, J D; Garrett, E D; Cullen, B R

    1993-01-01

    Human foamy virus encodes a 300-amino-acid nuclear regulatory protein termed Bel-1 that is required for human foamy virus replication in culture. Bel-1 is a potent trans-activator of gene expression directed by the homologous HFV long terminal repeat as well as the long terminal repeat of human immunodeficiency virus type 1. We have used mutational analysis to define several discrete functional domains within Bel-1. The C-terminal approximately 50 amino acids of Bel-1 are shown to be essential for Bel-1 activity but can be effectively substituted by the C-terminal activation domain of VP16. We therefore conclude that the Bel-1 C terminus forms part of an activation domain. Mutations within a central, approximately 100-amino-acid segment of Bel-1 preclude trans-activation by either Bel-1 or the Bel-1/VP16 chimera. These sequences are therefore proposed to direct the interaction of Bel-1 with its viral DNA target sequences. A short Bel-1 segment located between the activation and binding domains is shown to mediate the nuclear localization of this regulatory protein. Although the functional organization of Bel-1 therefore appears comparable to that reported for other eukaryotic transcriptional activators, Bel-1 does not contain sequences homologous to known transcriptional activation or DNA-binding motifs. Images PMID:8383217

  13. Approaches to Modelling the Dynamical Activity of Brain Function Based on the Electroencephalogram

    NASA Astrophysics Data System (ADS)

    Liley, David T. J.; Frascoli, Federico

    The brain is arguably the quintessential complex system as indicated by the patterns of behaviour it produces. Despite many decades of concentrated research efforts, we remain largely ignorant regarding the essential processes that regulate and define its function. While advances in functional neuroimaging have provided welcome windows into the coarse organisation of the neuronal networks that underlie a range of cognitive functions, they have largely ignored the fact that behaviour, and by inference brain function, unfolds dynamically. Modelling the brain's dynamics is therefore a critical step towards understanding the underlying mechanisms of its functioning. To date, models have concentrated on describing the sequential organisation of either abstract mental states (functionalism, hard AI) or the objectively measurable manifestations of the brain's ongoing activity (rCBF, EEG, MEG). While the former types of modelling approach may seem to better characterise brain function, they do so at the expense of not making a definite connection with the actual physical brain. Of the latter, only models of the EEG (or MEG) offer a temporal resolution well matched to the anticipated temporal scales of brain (mental processes) function. This chapter will outline the most pertinent of these modelling approaches, and illustrate, using the electrocortical model of Liley et al, how the detailed application of the methods of nonlinear dynamics and bifurcation theory is central to exploring and characterising their various dynamical features. The rich repertoire of dynamics revealed by such dynamical systems approaches arguably represents a critical step towards an understanding of the complexity of brain function.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. Statement--fundamental concepts of occupational therapy: occupation, purposeful activity, and function.

    PubMed

    Hinojosa, J; Kramer, P

    1997-01-01

    Deriving from the philosophical basis of the profession, occupation is the core concept of the profession of occupational therapy. However, in the occupational therapy literature, the term occupation is used in a variety of ways. Occupation, a collection of activities that people use to fill their time and give life meaning, is organized around roles or in terms of activities of daily living, work and productive activities, or pleasure, for survival, for necessity, and for their personal meaning. It is the individualized, unique combination of activities that comprises an individual's occupations. Purposeful activities have been described in many different ways: as something all people engage in; as tools or media that therapists use to enhance or facilitate performance; and vehicles for bringing about change. Purposeful activities are seen as part of the process of occupational therapy. Purposeful activities are subset of occupations in that they are goal directed and serve as a major tool in the process of occupational therapy. The term function, viewed as the ability to perform activities required in one's occupations has become increasingly important to society in describing the performance or change in individuals. This societal shift in ideas has prompted the concept of function, viewed as a product, to become more important than the process of bringing about change. Occupational therapy practitioners typically have viewed the process as being just as important as the product. When working to improve function, occupational therapy practitioners use purposeful activities that are meaningful to the person in relation to his or her occupational history, preferences, personal goals, and needs. Occupational therapy practitioners need to keep the individual's occupations in the forefront of their thoughts when using any purposeful activity and to plan interventions toward improving the individual's ability to function within his or her occupations. In the interest

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

    PubMed

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

    2016-02-01

    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

  20. Preoperative evaluation of activity and function in patients with paralytic scoliosis.

    PubMed

    Larsson, E L; Aaro, S; Ahlinder, P; Oberg, B

    1998-01-01

    Preoperative evaluation of patients with paralytic scoliosis should take into account the consequences of surgery on the every day life of the patient. However, the parameters that are customarily used in these operations relate only to very narrow measures such as the angle of scoliosis or kyphosis. The aim of this study was to introduce a set of instruments appropriate for measuring both function and activities in paralytic scoliosis patients. The study took as its starting point the WHO International Classification of Impairments, Disabilities and Handicaps (ICIDH), in which an activity is described at the level of the individual and function at the level of the organ. A consecutive series of 100 paralytic scoliosis patients with 18 different diagnoses were evaluated preoperatively with a set of instruments that had been specially developed at Linköping hospital, in which the variables are classified according to the system used in the ICIDH. The set of instruments included general information and evaluation of activities and function--sitting, balance, weight distribution to sitting surface, angle of scoliosis, reaching, pain estimation, activities of daily living (ADL) Barthel and ADL Klein and Bell, care given, time spent resting, and seating supports). The results showed that patients with paralytic scoliosis constitute a heterogeneous group in activities and function. Even when the patients were grouped into four subgroups according to the Scoliosis Research Society Classification, they remained very heterogeneous. However, reaching, Klein and Bell Activities of Daily Living and pain could only evaluate patients who could understand verbal instructions. In those who could not, assessment relied more heavily on measures of function and level of dependence. It was concluded that the choice of assessment must be guided by the patient's ability to understand verbal instructions irrespective of his/her disorder. It is important to use the three levels

  1. 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

  2. Mechanism of Epac activation: structural and functional analyses of Epac2 hinge mutants with constitutive and reduced activities.

    PubMed

    Tsalkova, Tamara; Blumenthal, Donald K; Mei, Fang C; White, Mark A; Cheng, Xiaodong

    2009-08-28

    Epac2 is a member of the family of exchange proteins directly activated by cAMP (Epac). Our previous studies suggest a model of Epac activation in which cAMP binding to the enzyme induces a localized "hinge" motion that reorients the regulatory lobe relative to the catalytic lobe without inducing large conformational changes within individual lobes. In this study, we identified the location of the major hinge in Epac2 by normal mode motion correlation and structural alignment analyses. Targeted mutagenesis was then performed to test the functional importance of hinge bending for Epac activation. We show that substitution of the conserved residue phenylalanine 435 with glycine (F435G) facilitates the hinge bending and leads to a constitutively active Epac2 capable of stimulating nucleotide exchange in the absence of cAMP. In contrast, substitution of the same residue with a bulkier side chain, tryptophan (F435W), impedes the hinge motion and results in a dramatic decrease in Epac2 catalytic activity. Structural parameters determined by small angle x-ray scattering further reveal that whereas the F435G mutant assumes a more extended conformation in the absence of cAMP, the F435W mutant is incapable of adopting the fully extended and active conformation in the presence of cAMP. These findings demonstrate the importance of hinge motion in Epac activation. Our study also suggests that phenylalanine at position 435 is the optimal size side chain to keep Epac closed and inactive in the absence of cAMP while still allowing the proper hinge motion for full Epac extension and activation in the presence of cAMP.

  3. Endostatin: A novel inhibitor of androgen receptor function in prostate cancer

    PubMed Central

    Lee, Joo Hyoung; Isayeva, Tatyana; Larson, Matthew R.; Sawant, Anandi; Cha, Ha-Ram; Chanda, Diptiman; Chesnokov, Igor N.; Ponnazhagan, Selvarangan

    2015-01-01

    Acquired resistance to androgen receptor (AR)-targeted therapies compels the development of novel treatment strategies for castration-resistant prostate cancer (CRPC). Here, we report a profound effect of endostatin on prostate cancer cells by efficient intracellular trafficking, direct interaction with AR, reduction of nuclear AR level, and down-regulation of AR-target gene transcription. Structural modeling followed by functional analyses further revealed that phenylalanine-rich α1-helix in endostatin—which shares structural similarity with noncanonical nuclear receptor box in AR—antagonizes AR transcriptional activity by occupying the activation function (AF)-2 binding interface for coactivators and N-terminal AR AF-1. Together, our data suggest that endostatin can be recognized as an endogenous AR inhibitor that impairs receptor function through protein–protein interaction. These findings provide new insights into endostatin whose antitumor effect is not limited to inhibiting angiogenesis, but can be translated to suppressing AR-mediated disease progression in CRPC. PMID:25605930

  4. Atrial conduction times and left atrium mechanical functions in patients with active acromegaly.

    PubMed

    Ilter, A; Kırış, A; Kaplan, Ş; Kutlu, M; Şahin, M; Erem, C; Civan, N; Kangül, F

    2015-03-01

    The aim of this study was to evaluate atrial electromechanical delay (EMD), P wave dispersion (Pwd), and left atrial (LA) mechanical functions in patients with active acromegaly. Twenty-three patients with active acromegaly and 27 age- and sex-matched controls were included in this study. All atrial electromechanical interval parameters (PA lateral, PA septum, PA tricuspid, interatrial EMD, intra-LA EMD, and intra-right atrial EMD) were measured from mitral lateral annulus, mitral septal annulus, and right ventricular tricuspid annulus by tissue Doppler imaging. LA volumes were measured by the disk method in the apical four-chamber view and were indexed to the body surface area. Mechanical function parameters of LA were calculated. Pwd was performed by 12-lead electrocardiograms. Atrial electromechanical intervals (PA lateral, PA septum, PA tricuspid, interatrial EMD, intra-LA EMD, and intra-right atrial EMD) and Pwd were similar between patients with acromegaly and control subjects (all p > 0.05). LA volumes (maximum, minimum, and presystolic) and LA mechanical functions were not significantly different between the groups (all p > 0.05). Additionally, serum levels of growth hormone and insulin-like growth factor-1 were not correlated with atrial electromechanical parameters and LA mechanical functions. Atrial electrical conduction times were not prolonged and LA mechanical functions were not impaired in patients with active acromegaly compared with controls. And the prevalence of supraventricular arrhythmia risk may not increase in this population.

  5. 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. PMID:25824728

  6. 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

  7. Functional response and population dynamics for fighting predator, based on activity distribution.

    PubMed

    Garay, József; Varga, Zoltán; Gámez, Manuel; Cabello, Tomás

    2015-03-01

    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.

  8. 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…

  9. 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…

  10. 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...

  11. 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…

  12. 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…

  13. 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...

  14. 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…

  15. 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…

  16. 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.

  17. 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.

  18. 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,…

  19. 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.

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 3 2014-04-01 2014-04-01 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...

  1. 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...

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false What functions and activities constitute program costs? 641.864 Section 641.864 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROVISIONS GOVERNING THE SENIOR COMMUNITY SERVICE EMPLOYMENT PROGRAM...

  3. 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.

  4. A TR-FRET-based functional assay for screening activators of CARM1.

    PubMed

    Zeng, Hao; Wu, Jiacai; Bedford, Mark T; Sbardella, Gianluca; Hoffmann, F Michael; Bi, Kun; Xu, Wei

    2013-05-10

    Epigenetics is an emerging field that demands selective cell-permeable chemical probes to perturb, especially in vivo, the activity of specific enzymes involved in modulating the epigenetic codes. Coactivator-associated arginine methyltransferase 1 (CARM1) is a coactivator of estrogen receptor α (ERα), the main target in human breast cancer. We previously showed that twofold overexpression of CARM1 in MCF7 breast cancer cells increased the expression of ERα-target genes involved in differentiation and reduced cell proliferation, thus leading to the hypothesis that activating CARM1 by chemical activators might be therapeutically effective in breast cancer. Selective, potent, cell-permeable CARM1 activators will be essential to test this hypothesis. Here we report the development of a cell-based, time-resolved (TR) FRET assay that uses poly(A) binding protein 1 (PABP1) methylation to monitor cellular activity of CARM1. The LanthaScreen TR-FRET assay uses MCF7 cells expressing GFP-PABP1 fusion protein through BacMam gene delivery system, methyl-PABP1 specific antibody, and terbium-labeled secondary antibody. This assay has been validated as reflecting the expression and/or activity of CARM1 and optimized for high throughput screening to identify CARM1 allosteric activators. This TR-FRET platform serves as a generic tool for functional screening of cell-permeable, chemical modulators of CARM1 for elucidation of its in vivo functions. PMID:23585185

  5. Functional activation of the egr-1 (early growth response-1) gene by hydrogen peroxide.

    PubMed

    Nose, K; Ohba, M

    1996-06-01

    The redox-based regulation of gene expression is one of the fundamental mechanisms of cellular functions, and hydrogen peroxide seems to act as an intracellular second messenger of signal transduction of cytokines. Hydrogen peroxide at non-toxic doses induced the accumulation of mRNA for the early growth response-1 (egr-1) gene in mouse osteoblastic cells. The Egr-1 protein is a transcription factor that binds the GCGGGGGCG sequence and contains a zinc-finger structure that is essential for DNA binding. Egr-1 protein is sensitive to oxidative stress and loses specific DNA-binding activity when exposed to high levels of oxidative stress. Incubating cells with hydrogen peroxide at about 50 microM, however, increased the accumulation of Egr-1 protein, and the Egr-1 product seemed to be functional, judging by its binding activity to the GCGGGGGCG sequence and its ability to activate the chloramphenicol acetyltransferase reporter gene under the control of the human thymidine kinase enhancer containing the Egr-1 binding sequence. It was reported that the activity of Egr-1 protein as a transcription factor was negatively regulated by active oxygens. However, with appropriate concentrations of active oxygen, its capacity to bind a specific DNA sequence and to enhance the transcriptional activity of target genes is thought to be elevated.

  6. ASSESSMENT OF UPPER EXTREMITY IMPAIRMENT, FUNCTION, AND ACTIVITY FOLLOWING STROKE: FOUNDATIONS FOR CLINICAL DECISION MAKING

    PubMed Central

    Lang, Catherine E.; Bland, Marghuretta D.; Bailey, Ryan R.; Schaefer, Sydney Y.; Birkenmeier, Rebecca L.

    2012-01-01

    The purpose of this review is to provide a comprehensive approach for assessing the upper extremity (UE) after stroke. First, common upper extremity impairments and how to assess them are briefly discussed. While multiple UE impairments are typically present after stroke, the severity of one impairment, paresis, is the primary determinant of UE functional loss. Second, UE function is operationally defined and a number of clinical measures are discussed. It is important to consider how impairment and loss of function affect UE activity outside of the clinical environment. Thus, this review also identifies accelerometry as an objective method for assessing UE activity in daily life. Finally, the role that each of these levels of assessment should play in clinical decision making is discussed in order to optimize the provision of stroke rehabilitation services. PMID:22975740

  7. Beta-globin locus activation regions: conservation of organization, structure, and function.

    PubMed

    Li, Q L; Zhou, B; Powers, P; Enver, T; Stamatoyannopoulos, G

    1990-11-01

    The human beta-globin locus activation region (LAR) comprises four erythroid-specific DNase I hypersensitive sites (I-IV) thought to be largely responsible for activating the beta-globin domain and facilitating high-level erythroid-specific globin gene expression. We identified the goat beta-globin LAR, determined 10.2 kilobases of its sequence, and demonstrated its function in transgenic mice. The human and goat LARs share 6.5 kilobases of homologous sequences that are as highly conserved as the epsilon-globin gene promoters. Furthermore, the overall spatial organization of the two LARs has been conserved. These results suggest that the functionally relevant regions of the LAR are large and that in addition to their primary structure, the spatial relationship of the conserved elements is important for LAR function.

  8. Relationships among solar activity SEP occurrence frequency, and solar energetic particle event distribution function

    NASA Astrophysics Data System (ADS)

    Nymmik, Rikho

    The solar cycle 20-22 direct spacecraft measurement results are used to analyze the occurrence frequency and distribution function of solar energetic particle (SEP) events as dependent on solar activity. The analysis has shown that • the mean occurrence frequency of the SEP events with ≥30 MeV proton fluence sizes exceeding 106 is proportional to sunspot number, • the SEP event proton distribution functions for periods of different solar activity levels can be described to be power-law functions whose spectral form (spectral indices and cutoff values) are the same. The above results permit the following conclusions: a) to within statistical deviations, the total number of SEP events observed during any given time interval is proportional to the sum of mean-yearly sunspot numbers; b) large SEP events can occur to within quite a definite probability even during solar minima.

  9. Executive cognitive function as a correlate and predictor of child food intake and physical activity.

    PubMed

    Riggs, Nathaniel; Chou, Chih-Ping; Spruijt-Metz, Donna; Pentz, Mary Ann

    2010-01-01

    Investigated were relations among executive cognitive function (ECF), food intake, and physical activity in 184, fourth grade children. It was hypothesized that self-reported ECF proficiency would predict greater self-reported fruit/vegetable intake and physical activity, but less "snack food" intake. Structural models demonstrated that ECF was significantly correlated with less concurrent snack food intake and greater concurrent fruit/vegetable intake, but not physical activity. Baseline ECF also significantly predicted greater fruit/vegetable intake and physical activity four months later, but not snack food intake. One implication is to promote ECF as a correlate and predictor of food intake and physical activity in children by providing opportunities for youth to practice newly developing ECF capacities.

  10. The macrophage response to bacteria. Modulation of macrophage functional activity by peptidoglycan from Moraxella (Branhamella) catarrhalis.

    PubMed Central

    Keller, R; Gustafson, J E; Keist, R

    1992-01-01

    Moraxella (Branhamella) catarrhalis organisms have been shown to be particularly efficient in inducing in a pure population of bone marrow-derived mononuclear phagocytes secretory and cellular activities. In the present study, the ability of peptidoglycan from this Gram-negative organism to trigger a macrophage response was compared with that elicited by peptidoglycan from Staphylococcus aureus and Bacillus subtilis. The results show that the three peptidoglycans were similarly active in triggering the secretion of tumour necrosis factor and tumouricidal activity but differed considerably in their ability to induce the generation of nitrite in macrophages; in this respect, peptidoglycan from M. catarrhalis was particularly potent. The impressive capacity of M. catarrhalis peptidoglycan to induce in low concentration the secretion of tumour necrosis factor and nitrite and tumouricidal activity may, in addition to its lipopolysaccharide, contribute to the extraordinary potential of this organism to trigger the functional activities of macrophages. PMID:1516255

  11. 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

  12. 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

  13. Activation detection in functional near-infrared spectroscopy by wavelet coherence.

    PubMed

    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. PMID:25562502

  14. Carbohydrate-functionalized nanovaccines preserve HIV-1 antigen stability and activate antigen presenting cells

    PubMed Central

    Vela Ramirez, J.E.; Roychoudhury, R.; Habte, H.H.; Cho, M. W.; Pohl, N. L. B.; Narasimhan, B.

    2015-01-01

    The functionalization of polymeric nanoparticles with ligands that target specific receptors on immune cells offers the opportunity to tailor adjuvant properties by conferring pathogen mimicking attributes to the particles. Polyanhydride nanoparticles are promising vaccine adjuvants with desirable characteristics such as immunomodulation, sustained antigen release, activation of antigen presenting cells, and stabilization of protein antigens. These capabilities can be exploited to design nanovaccines against viral pathogens, such as HIV-1, due to the important role of dendritic cells and macrophages in viral spread. In this work, an optimized process was developed for carbohydrate functionalization of HIV-1 antigen-loaded polyanhydride nanoparticles. The carbohydrate-functionalized nanoparticles preserved antigenic properties upon release and also enabled sustained antigen release kinetics. Particle internalization was observed to be chemistry-dependent with positively charged nanoparticles being taken up more efficiently by dendritic cells. Up-regulation of the activation makers CD40 and CD206 was demonstrated with carboxymethyl-α-d-mannopyranosyl-(1,2)-d-mannopyranoside functionalized nanoparticles. The secretion of the cytokines IL-6 and TNF-α was shown to be chemistry-dependent upon stimulation with carbohydrate-functionalized nanoparticles. These results offer important new insights upon the interactions between carbohydrate-functionalized nanoparticles and antigen presenting cells and provide foundational information for the rational design of targeted nanovaccines against HIV-1. PMID:25068589

  15. Carbohydrate-functionalized nanovaccines preserve HIV-1 antigen stability and activate antigen presenting cells.

    PubMed

    Vela Ramirez, J E; Roychoudhury, R; Habte, H H; Cho, M W; Pohl, N L B; Narasimhan, B

    2014-01-01

    The functionalization of polymeric nanoparticles with ligands that target specific receptors on immune cells offers the opportunity to tailor adjuvant properties by conferring pathogen mimicking attributes to the particles. Polyanhydride nanoparticles are promising vaccine adjuvants with desirable characteristics such as immunomodulation, sustained antigen release, activation of antigen presenting cells (APCs), and stabilization of protein antigens. These capabilities can be exploited to design nanovaccines against viral pathogens, such as HIV-1, due to the important role of dendritic cells (DCs) and macrophages in viral spread. In this work, an optimized process was developed for carbohydrate functionalization of HIV-1 antigen-loaded polyanhydride nanoparticles. The carbohydrate-functionalized nanoparticles preserved antigenic properties upon release and also enabled sustained antigen release kinetics. Particle internalization was observed to be chemistry-dependent with positively charged nanoparticles being taken up more efficiently by DCs. Up-regulation of the activation makers CD40 and CD206 was demonstrated with carboxymethyl-α-d-mannopyranosyl-(1,2)-d-mannopyranoside functionalized nanoparticles. The secretion of the cytokines IL-6 and TNF-α was shown to be chemistry-dependent upon stimulation with carbohydrate-functionalized nanoparticles. These results offer important new insights upon the interactions between carbohydrate-functionalized nanoparticles and APCs and provide foundational information for the rational design of targeted nanovaccines against HIV-1. PMID:25068589

  16. Activation of the aryl hydrocarbon receptor affects activation and function of human monocyte-derived dendritic cells.

    PubMed

    Wang, C; Ye, Z; Kijlstra, A; Zhou, Y; Yang, P

    2014-08-01

    Aryl hydrocarbon receptor (AhR) is well known for mediating the toxic effects of dioxin-containing pollutants, but has also been shown to be involved in the natural regulation of the immune response. In this study, we investigated the effect of AhR activation by its endogenous ligands 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the differentiation, maturation and function of monocyte-derived DCs in Behçet's disease (BD) patients. In this study, we showed that AhR activation by FICZ and ITE down-regulated the expression of co-stimulatory molecules including human leucocyte antigen D-related (HLA-DR), CD80 and CD86, while it had no effect on the expression of CD83 and CD40 on DCs derived from BD patients and normal controls. Lipopolysaccharide (LPS)-treated dendritic cells (DCs) from active BD patients showed a higher level of interleukin (IL)-1β, IL-6, IL-23 and tumour necrosis factor (TNF)-α production. FICZ or ITE significantly inhibited the production of IL-1β, IL-6, IL-23 and TNF-α, but induced IL-10 production by DCs derived from active BD patients and normal controls. FICZ or ITE-treated DCs significantly inhibited the T helper type 17 (Th17) and Th1 cell response. Activation of AhR either by FICZ or ITE inhibits DC differentiation, maturation and function. Further studies are needed to investigate whether manipulation of the AhR pathway may be used to treat BD or other autoimmune diseases.

  17. Genetic dissection of the phospholipid hydroperoxidase activity of yeast gpx3 reveals its functional importance.

    PubMed

    Avery, Angela M; Willetts, Sylvia A; Avery, Simon V

    2004-11-01

    Saccharomyces cerevisiae expresses multiple phospholipid hydroperoxide glutathione peroxidase (PHGPx)-like proteins in the absence of a classical glutathione peroxidase (cGPx), providing a unique system for dissecting the roles of these enzymes in vivo. The Gpx3 (Orp1/PHGpx3) protein transduces the hydroperoxide signal to the transcription factor Yap1, a function that could account for most GPX-dependent phenotypes. To test this hypothesis and ascertain what functions of Gpx3 can be shared by cGPx-like enzymes, we constructed a novel cGPx-like yeast enzyme, cGpx3. We confirmed that the "gap" sequences conserved among cGPxs but absent from aligned PHGPx sequences are the principal cause of the structural and functional differences of these enzymes. Peroxidase activity against a cGPx substrate was high in the cGpx3 construct, which was multimeric and had a peroxidase catalytic mechanism distinct from Gpx3; but cGpx3 was defective for phospholipid hydroperoxidase and signaling activities. cGpx3 did not complement the sensitivity to lipid peroxidation of a gpxDelta mutant, and the resistance to lipid peroxidation conferred by Gpx3 was independent of Yap1, establishing a functional role for Gpx3 phospholipid hydroperoxidase activity. Using the comparison between cGpx3 and Gpx3 in conjunction with other constructs to probe lipid peroxidation as a toxicity mechanism, we also ascertained that lipid peroxidation-dependent processes are a principal cause of cellular cadmium toxicity. The results demonstrate that phospholipid hydroperoxidase and Yap1-mediated signaling activities of Gpx3 have independent functional roles, although both functions depend on the absence of cGPx-like subunit interaction sites, and the results resolve more clearly the potential drivers of the differential selective evolution of GPx-like enzymes. PMID:15337745

  18. Characterizing cerebellar activity during autobiographical memory retrieval: ALE and functional connectivity investigations.

    PubMed

    Addis, Donna Rose; Moloney, Eleanor E J; Tippett, Lynette J; P Roberts, Reece; Hach, Sylvia

    2016-09-01

    Previous neuroimaging research has shown that the cerebellum is often activated during autobiographical memory (AM) retrieval. However, the reliability of that activation, its localization within the cerebellum, and its relationship to other areas of the AM network remains unknown. The current study used Activation Likelihood Estimation meta-analysis (ALE) as well as resting-state and task-related functional connectivity analyses to better characterize cerebellar activation in relation to AM. The ALE meta-analysis was run on 32 neuroimaging studies of AM retrieval. The results revealed a cluster of reliable AM-related activity within the Crus I lobule of the right posterior cerebellum. Using the peak ALE coordinate within Crus I as a seed region, both task-related and resting state functional connectivity analyses were run on fMRI data from 38 healthy participants. To determine the specificity of connectivity patterns to Crus I, we also included a cerebellar seed region in right Lobule VI previously identified in an ALE meta-analysis as associated with working memory. Resting-state functional connectivity analyses indicated that Crus I was intrinsically connected with other areas of the AM network as well as surrounding and contralateral cerebellar regions. In contrast, the Lobule VI seed was functionally connected with cerebral and cerebellar regions typically associated with working memory. The task-related connectivity analyses revealed a similar pattern, where the Crus I seed exhibited significant connectivity with key nodes of the AM network while the Lobule IV seed did not. During a semantic control task, both Crus I and Lobule VI showed significant correlations with a network of regions that was largely distinct from the AM network. Together these results indicate that right Crus I lobule is reliably engaged during AM retrieval and is functionally connected to the AM network both during rest, and more importantly, during AM retrieval. PMID:27235570

  19. Transforming community prevention systems for sustained impact: embedding active implementation and scaling functions.

    PubMed

    Aldridge, William A; Boothroyd, Renée I; Fleming, W Oscar; Lofts Jarboe, Karen; Morrow, Jane; Ritchie, Gail F; Sebian, Joyce

    2016-03-01

    Traditional efforts to translate evidence-based prevention strategies to communities, at scale, have not often produced socially significant outcomes or the local capacity needed to sustain them. A key gap in many efforts is the transformation of community prevention systems to support and sustain local infrastructure for the active implementation, scaling, and continuous improvement of effective prevention strategies. In this paper, we discuss (1) the emergence of applied implementation science as an important type 3-5 translational extension of traditional type 2 translational prevention science, (2) active implementation and scaling functions to support the full and effective use of evidence-based prevention strategies in practice, (3) the organization and alignment of local infrastructure to embed active implementation and scaling functions within community prevention systems, and (4) policy and practice implications for greater social impact and sustainable use of effective prevention strategies. PMID:27012261

  20. Functionally Active Gap Junctions between Connexin 43-Positive Mesenchymal Stem Cells and Glioma Cells.

    PubMed

    Gabashvili, A N; Baklaushev, V P; Grinenko, N F; Levinskii, A B; Mel'nikov, P A; Cherepanov, S A; Chekhonin, V P

    2015-05-01

    The formation of functional gap junctions between mesenchymal stem cells and cells of low-grade rat glioma C6 cells was studied in in vitro experiments. Immunocytochemical analysis with antibodies to connexin 43 extracellular loop 2 showed that mesenchymal stem cells as well as C6 glioma cells express the main astroglial gap junction protein connexin 43. Analysis of migration activity showed that mesenchymal stem cells actively migrate towards C6 glioma cells. During co-culturing, mesenchymal stem cells and glioma C6 form functionally active gap junctions mediating the transport of cytoplasmic dye from glioma cells to mesenchymal stem cells in the opposite direction. Fluorometry showed that the intensity of transport of low-molecular substances through heterologous gap junctions between mesenchymal stem cells and glioma cells is similar to that through homologous gap junctions between glioma cells. This phenomenon can be used for the development of new methods of cell therapy of high-grade gliomas.

  1. Physical activity ameliorates cardiovascular health in elderly subjects: the functional role of the β adrenergic system

    PubMed Central

    Santulli, Gaetano; Ciccarelli, Michele; Trimarco, Bruno; Iaccarino, Guido

    2013-01-01

    Aging is a complex process characterized by a gradual decline in organ functional reserves, which eventually reduces the ability to maintain homeostasis. An exquisite feature of elderly subjects, which constitute a growing proportion of the world population, is the high prevalence of cardiovascular disorders, which negatively affect both the quality of life and the life expectancy. It is widely acknowledged that physical activity represents one of the foremost interventions capable in reducing the health burden of cardiovascular disease. Interestingly, the benefits of moderate-intensity physical activity have been established both in young and elderly subjects. Herein we provide a systematic and updated appraisal of the literature exploring the pathophysiological mechanisms evoked by physical activity in the elderly, focusing on the functional role of the β adrenergic system. PMID:23964243

  2. p38 mitogen-activated protein kinase activation during platelet storage: consequences for platelet recovery and hemostatic function in vivo

    PubMed Central

    Canault, Matthias; Duerschmied, Daniel; Brill, Alexander; Stefanini, Lucia; Schatzberg, Daphne; Cifuni, Stephen M.

    2010-01-01

    Platelets undergo several modifications during storage that reduce their posttransfusion survival and functionality. One important feature of these changes, which are known as platelet storage lesion, is the shedding of the surface glycoproteins GPIb-α and GPV. We recently demonstrated that tumor necrosis factor-α converting enzyme (TACE/ADAM17) mediates mitochondrial injury-induced shedding of adhesion receptors and that TACE activity correlates with reduced posttransfusion survival of these cells. We now confirm that TACE mediates receptor shedding and clearance of platelets stored for 16 hours at 37°C or 22°C. We further demonstrate that both storage and mitochondrial injury lead to the phosphorylation of p38 mitogen-activated kinase (MAPK) in platelets and that TACE-mediated receptor shedding from mouse and human platelets requires p38 MAP kinase signaling. Protein kinase C, extracellular regulated-signal kinase MAPK, and caspases were not involved in TACE activation. Both inhibition of p38 MAPK and inactivation of TACE during platelet storage led to a markedly improved posttransfusion recovery and hemostatic function of platelets in mice. p38 MAPK inhibitors had only minor effects on the aggregation of fresh platelets under static or flow conditions in vitro. In summary, our data suggest that inhibition of p38 MAPK or TACE during storage may significantly improve the quality of stored platelets. PMID:19965619

  3. p38 mitogen-activated protein kinase activation during platelet storage: consequences for platelet recovery and hemostatic function in vivo.

    PubMed

    Canault, Matthias; Duerschmied, Daniel; Brill, Alexander; Stefanini, Lucia; Schatzberg, Daphne; Cifuni, Stephen M; Bergmeier, Wolfgang; Wagner, Denisa D

    2010-03-01

    Platelets undergo several modifications during storage that reduce their posttransfusion survival and functionality. One important feature of these changes, which are known as platelet storage lesion, is the shedding of the surface glycoproteins GPIb-alpha and GPV. We recently demonstrated that tumor necrosis factor-alpha converting enzyme (TACE/ADAM17) mediates mitochondrial injury-induced shedding of adhesion receptors and that TACE activity correlates with reduced posttransfusion survival of these cells. We now confirm that TACE mediates receptor shedding and clearance of platelets stored for 16 hours at 37 degrees C or 22 degrees C. We further demonstrate that both storage and mitochondrial injury lead to the phosphorylation of p38 mitogen-activated kinase (MAPK) in platelets and that TACE-mediated receptor shedding from mouse and human platelets requires p38 MAP kinase signaling. Protein kinase C, extracellular regulated-signal kinase MAPK, and caspases were not involved in TACE activation. Both inhibition of p38 MAPK and inactivation of TACE during platelet storage led to a markedly improved posttransfusion recovery and hemostatic function of platelets in mice. p38 MAPK inhibitors had only minor effects on the aggregation of fresh platelets under static or flow conditions in vitro. In summary, our data suggest that inhibition of p38 MAPK or TACE during storage may significantly improve the quality of stored platelets.

  4. Functional MRI of neuronal activation in epilepsy patients with malformations of cortical development.

    PubMed

    Nikolova, Simona; Bartha, Robert; Parrent, Andrew G; Steven, David A; Diosy, David; Burneo, Jorge G

    2015-10-01

    Malformations of cortical development are disturbances in brain formation that arise from abnormalities affecting the processes of cortical development. Surgical treatment of intractable epilepsy in patients with malformations of cortical development requires localization of both epileptogenic and eloquent cortices. Functional magnetic resonance imaging has been shown to detect the reorganization of activation patterns in such patients. The purpose of this study was to determine whether functional reorganization of the primary sensory and motor cortices occurs in patients with epileptogenic malformations of cortical development. Functional MRI data were obtained for 11 patients (four male, seven female) with a mean age of 36 years (range 18-55 years). The mean age at epilepsy onset was 23 years (range 3-55 years). Twelve healthy controls (six male, six female) with mean age of 33 years (range 28-51 years) were also recruited for comparison. High resolution anatomical MRI was used to confirm the presence and the location of the malformation. All imaging experiments were performed using a 3.0T Siemens Tim Trio whole body MRI. Each subject performed four block-paradigm fMRI experiments to study motor and sensory activation for each hand. A total of 132 image sets were collected for each paradigm over 5.5min (2.5s per image). Each paradigm consisted of seven stimulus periods lasting 30s (12 images) and stimulus onset of 30, 90, 150, 210 and 270s. Functional data were obtained from all eligible patients and compared to those of controls. Reorganization and reduction in function in the motor and sensory areas were observed in patients with cortical dysplasia. Patients with polymicrogyria did not present with significant functional reorganization and patients with heterotopias and coexisting polymicrogyria and/or cortical dysplasia had variable patterns of activation. In summary, this study showed evidence of functional reorganization of sensory and motor cortices in

  5. 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

  6. Cognitive activity, cognitive function, and brain diffusion characteristics in old age.

    PubMed

    Arfanakis, Konstantinos; Wilson, Robert S; Barth, Christopher M; Capuano, Ana W; Vasireddi, Anil; Zhang, Shengwei; Fleischman, Debra A; Bennett, David A

    2016-06-01

    The objective of this work was to test the hypotheses that a) more frequent cognitive activity in late life is associated with higher brain diffusion anisotropy and lower trace of the diffusion tensor, and b) brain diffusion characteristics partially mediate the association of late life cognitive activity with cognition. As part of a longitudinal cohort study, 379 older people without dementia rated their frequency of participation in cognitive activities, completed a battery of cognitive function tests, and underwent diffusion tensor imaging. We used tract-based spatial statistics to test the association between late life cognitive activity and brain diffusion characteristics. Clusters with statistically significant findings defined regions of interest in which we tested the hypothesis that diffusion characteristics partially mediate the association of late life cognitive activity with cognition. More frequent cognitive activity in late life was associated with higher level of global cognition after adjustment for age, sex, education, and indicators of early life cognitive enrichment (p = 0.001). More frequent cognitive activity was also related to higher fractional anisotropy in the left superior and inferior longitudinal fasciculi, left fornix, and corpus callosum, and lower trace in the thalamus (p < 0.05, FWE-corrected). After controlling for fractional anisotropy or trace from these regions, the regression coefficient for the association of late life cognitive activity with cognition was reduced by as much as 26 %. These findings suggest that the association of late life cognitive activity with cognition may be partially mediated by brain diffusion characteristics.

  7. Identifying functional subdivisions in the human brain using meta-analytic activation modeling-based parcellation.

    PubMed

    Yang, Yong; Fan, Lingzhong; Chu, Congying; Zhuo, Junjie; Wang, Jiaojian; Fox, Peter T; Eickhoff, Simon B; Jiang, Tianzi

    2016-01-01

    Parcellation of the human brain into fine-grained units by grouping voxels into distinct clusters has been an effective approach for delineating specific brain regions and their subregions. Published neuroimaging studies employing coordinate-based meta-analyses have shown that the activation foci and their corresponding behavioral categories may contain useful information about the anatomical-functional organization of brain regions. Inspired by these developments, we proposed a new parcellation scheme called meta-analytic activation modeling-based parcellation (MAMP) that uses meta-analytically obtained information. The raw meta data, including the experiments and the reported activation coordinates related to a brain region of interest, were acquired from the Brainmap database. Using this data, we first obtained the "modeled activation" pattern by modeling the voxel-wise activation probability given spatial uncertainty for each experiment that featured at least one focus within the region of interest. Then, we processed these "modeled activation" patterns across the experiments with a K-means clustering algorithm to group the voxels into different subregions. In order to verify the reliability of the method, we employed our method to parcellate the amygdala and the left Brodmann area 44 (BA44). The parcellation results were quite consistent with previous cytoarchitectonic and in vivo neuroimaging findings. Therefore, the MAMP proposed in the current study could be a useful complement to other methods for uncovering the functional organization of the human brain.

  8. [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.

  9. 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.

  10. 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

  11. Platelet function and fibrinolytic activity during rest and exercise in borderline hypertensive patients.

    PubMed

    Gleerup, G; Vind, J; Winther, K

    1995-04-01

    In this study we examined whether the reduced fibrinolysis and increased platelet activity that are known to occur in hypertension are already present in borderline hypertension. Twelve patients with 'borderline' hypertension (diastolic blood pressure 90-95 mmHg) were found to have substantially reduced fibrinolytic activity, both at rest and during exercise, compared with 12 normotensive controls. Euglobulin clot lysis time (ECLT) was significantly higher in hypertensive subjects (218 min vs. 145 min; P < 0.05), and this difference persisted during exercise. Resting tissue plasminogen activator activity (t-PA) did not differ in the two groups, but the brisk increase in t-PA in controls during exercise (0.64 rising to 1.44 IU mL-1; P < 0.01) did not occur to the same extent in the borderline hypertensive subjects. Levels of the fast-acting t-PA inhibitor, normally referred to as PAI-1, were considerably higher in hypertensives (9.22 vs. 4.41 IU mL-1; P < 0.02), and this difference persisted in the upright posture, indicating a decrease in fibrinolytic activity. Platelet aggregability induced by ADP in vitro was not significantly higher in the hypertensive subjects, but indices of platelet activity in vivo (B-TG and PF-4 levels) revealed enhanced platelet function in the hypertensives. These results indicate that the indicators of altered haemostatic function known to occur in hypertension, namely diminished fibrinolytic activity and increased platelet function, are already detectable during the very earliest stage of the disease.

  12. Cellular senescence checkpoint function determines differential Notch1-dependent oncogenic and tumor suppressor activities

    PubMed Central

    Kagawa, Shingo; Natsuizaka, Mitsuteru; Whelan, Kelly A.; Facompre, Nicole; Naganuma, Seiji; Ohashi, Shinya; Kinugasa, Hideaki; Egloff, Ann Marie; Basu, Devraj; Gimotty, Phyllis A.; Klein-Szanto, Andres J; Bass, Adam; Wong, Kwok-Kin; Diehl, J. Alan; Rustgi, Anil K.; Nakagawa, Hiroshi

    2014-01-01

    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 (RNAi) 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 p16INK4A-Rb pathway. Loss of p16INK4A 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 TGF-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. PMID:24931169

  13. 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.

  14. Age-related decrease in physical activity and functional fitness among elderly men and women

    PubMed Central

    Milanović, Zoran; Pantelić, Saša; Trajković, Nebojša; Sporiš, Goran; Kostić, Radmila; James, Nic

    2013-01-01

    Aim To determine differences in physical activity level and functional fitness between young elderly (60–69 years) and old elderly (70–80 years) people with the hypothesis that an age-related decline would be found. Methods A total of 1288 participants’ level of physical activity was evaluated using the International Physical Activity Questionnaire: 594 were male (mean ± standard deviation: body height 175.62 ± 9.78 cm; body weight 82.26 ± 31.33 kg) and 694 female (mean ± standard deviation: body height 165.17 ± 23.12 cm; body weight 69.74 ± 12.44 kg). Functional fitness was also estimated using the Senior Fitness Test: back scratch, chair sit and reach, 8-foot up and go, chair stand up for 30 seconds, arm curl, and 2-minute step test. Results Significant differences (P < 0.05) were found for all Senior Fitness tests between young elderly (60–69 years) and old elderly (70–80) men. Similar results were found for the women, except no significant differences were found for the chair sit and reach and the 2-minute step test. From the viewpoint of energy consumption estimated by the International Physical Activity Questionnaire, moderate physical activity is dominant. In addition, with aging, among men and women older than 60 years, the value of the Metabolic Equivalent of Task in total physical activity significantly reduces (P < 0.05). Conclusions This study found that the reduction in physical activity level and functional fitness was equal for both men and women and was due to the aging process. These differences between young and old elderly people were due to the reduction of muscle strength in both upper and lower limbs and changes in body-fat percentage, flexibility, agility, and endurance. PMID:23723694

  15. 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.

  16. 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

  17. 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

  18. Surface activity and flocculation behavior of polyethylene glycol-functionalized silica nanoparticles.

    PubMed

    Björkegren, Sanna Maria Sofi; Nordstierna, Lars; Törncrona, Anders; Persson, Michael E; Palmqvist, Anders E C

    2015-08-15

    Colloidal silica nanoparticles have been functionalized with methyl polyethylene glycol silane (mPEG silane) and the PEGylated particles have been characterized with focus on exploring their surface chemical properties. The degree of surface functionalization was quantified using NMR diffusometry, and the measurements showed that the silane binds covalently to the silica surface. Samples with surface coverages ranging from 0.068 to 0.315 μmol silane/m(2) have been analyzed. The functionalized particles proved to be surface active and showed a significant reduction in surface charge and zeta potential with increasing degree of PEG functionalization. All samples showed colloidal stability at neutral pH and above within the range studied. At lower pH, the samples with low surface coverage displayed a reversible flocculation behavior, while samples with a high surface coverage and samples without functionalization remained stable. This suggests that steric stabilization is effective at low pH when the surface coverage is high enough; electrostatic stabilization is effective for samples without functionalization; and that inter-particle PEG-silica interactions cause flocculation of particles with too low degrees of PEG functionalization.

  19. Activated protein C: A regulator of human skin epidermal keratinocyte function.

    PubMed

    McKelvey, Kelly; Jackson, Christopher John; Xue, Meilang

    2014-05-26

    Activated protein C (APC) is a physiological anticoagulant, derived from its precursor protein C (PC). Independent of its anticoagulation, APC possesses strong anti-inflammatory, anti-apoptotic and barrier protective properties which appear to be protective in a number of disorders including chronic wound healing. The epidermis is the outermost skin layer and provides the first line of defence against the external environment. Keratinocytes are the most predominant cells in the epidermis and play a critical role in maintaining epidermal barrier function. PC/APC and its receptor, endothelial protein C receptor (EPCR), once thought to be restricted to the endothelium, are abundantly expressed by skin epidermal keratinocytes. These cells respond to APC by upregulating proliferation, migration and matrix metalloproteinase-2 activity and inhibiting apoptosis/inflammation leading to a wound healing phenotype. APC also increases barrier function of keratinocyte monolayers by promoting the expression of tight junction proteins and re-distributing them to cell-cell contacts. These cytoprotective properties of APC are mediated through EPCR, protease-activated receptors, epidermal growth factor receptor or Tie2. Future preventive and therapeutic uses of APC in skin disorders associated with disruption of barrier function and inflammation look promising. This review will focus on APC's function in skin epidermis/keratinocytes and its therapeutical potential in skin inflammatory conditions.

  20. Effects of mental practice on stroke patients’ upper extremity function and daily activity performance

    PubMed Central

    Park, JuHyung; Lee, Nayun; Cho, Milim; Kim, DeokJu; Yang, Yeongae

    2015-01-01

    [Purpose] The purpose of this study was to evaluate the effects of mental practice on stroke patients’ upper extremity function and activities of daily living (ADL). [Subjects and Methods] In this study, 29 stroke patients were randomly assigned to two groups: an experimental group (n=14) and a control group (n=15). The experimental group performed 10 minutes of mental practice once a day, 5 days a week for 2 weeks in combination with conventional rehabilitation therapy. For the control group, general rehabilitation therapy was provided during the same sessions as the experimental group. The Action Research Arm Test (ARAT) and the Fugl-Myer assessment (FMA) were used to measure upper extremity function, and the Modified Bathel Index (MBI) was used to measure daily activity performance. [Results] After the intervention, the mental practice group showed significant improvements in upper extremity function on the affected side and ADL scores compared to the control group. [Conclusion] The results of this study demonstrate mental practice intervention is effective at improving stroke patients’ upper extremity function and daily activity performance. In follow-up studies, securing a greater number of experimental subjects, and evaluation of the intervention’s therapeutic durability are required. PMID:25995560

  1. Brain activation to negative stimuli mediates a relationship between adolescent marijuana use and later emotional functioning.

    PubMed

    Heitzeg, Mary M; Cope, Lora M; Martz, Meghan E; Hardee, Jillian E; Zucker, Robert A

    2015-12-01

    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

  2. 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

  3. Liver injury in hypervitaminosis A: Evidence for activation of Kupffer cell function

    SciTech Connect

    Sim, W.L.W.

    1988-01-01

    The most important and novel finding of this work was enhanced liver Kupffer cell phagocytic and metabolic function by hypervitaminosis A. An animal model of hypervitaminosis A was developed in male Sprague-Dawley rats gavaged with 250,000 I.U. retinol/kg body weight/day for 3 weeks. Presence of hypervitaminosis A was indicated by characteristic changes in the fur coat, presence of brittle bones and spontaneous fractures and a significant increase in plasma and liver concentrations of retinyl palmitate while retinol levels remained the same as in controls. Hypervitaminosis A did not cause severe liver abnormalities as reflected by normal plasma glutamate pyruvate transaminase activity and bilirubin. The main change was a marked increase in size of the fat or Vitamin A storing cells. Measurement of clearance from blood of indocyanine green and {sup 99m}Tc-disofenin indicated this hepatocyte function was normal. Kupffer cell phagocytic function was enhanced in hypervitaminosis A as determined by clearance from blood of {sup 99m}Tc-sulfur colloid. In vitro, there was also evidence that treatment with high doses of Vitamin A activated or enhanced Kupffer cell function. Kupffer cells from control and Vitamin A treated rats were isolated by enzymatic dispersion, purified by centrifugal elutriation, and placed in culture. Activation was indicated by (1) increased phagocytosis of {sup 51}Cr-labeled opsonized sheep red blood cells (2) enhanced release of superoxide anion and (3) enhanced production of tumor cytolytic factor by Kupffer cells from Vitamin A treated rats.

  4. Developmental changes in brain activation and functional connectivity during response inhibition in the early childhood brain.

    PubMed

    Mehnert, Jan; Akhrif, Atae; Telkemeyer, Silke; Rossi, Sonja; Schmitz, Christoph H; Steinbrink, Jens; Wartenburger, Isabell; Obrig, Hellmuth; Neufang, Susanne

    2013-11-01

    Response inhibition is an attention function which develops relatively early during childhood. Behavioral data suggest that by the age of 3, children master the basic task requirements for the assessment of response inhibition but performance improves substantially until the age of 7. The neuronal mechanisms underlying these developmental processes, however, are not well understood. In this study, we examined brain activation patterns and behavioral performance of children aged between 4 and 6 years compared to adults by applying a go/no-go paradigm during near-infrared spectroscopy (NIRS) brain imaging. We furthermore applied task-independent functional connectivity measures to the imaging data to identify maturation of intrinsic neural functional networks. We found a significant group×condition related interaction in terms of inhibition-related reduced right fronto-parietal activation in children compared to adults. In contrast, motor-related activation did not differ between age groups. Functional connectivity analysis revealed that in the children's group, short-range coherence within frontal areas was stronger, and long-range coherence between frontal and parietal areas was weaker, compared to adults. Our findings show that in children aged from 4 to 6 years fronto-parietal brain maturation plays a crucial part in the cognitive development of response inhibition. PMID:23265620

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. Inorganic lead exposure in battery and paint factory: effect on human sperm structure and functional activity.

    PubMed

    Naha, N; Chowdhury, A Roy

    2006-06-01

    Lead is one of the industrially important heavy metals that causes male reproductive impairment among battery and paint factory workers, but information on the structure-function integrity of human spermatozoa is still limited. Therefore, it was necessary to investigate the effect of lead on sperm structure and functional activity in these workers. Oligozoospermia with concomitant lowering of sperm protein and nucleic acid content and the percentage of sperm DNA hyploidy (P <0.001) suggested the diminution of sperm cell production after occupational lead exposure. Low sperm vitality and hypoosmotic swelling percentage along with high malondialdehyde content and altered seminal plasma ascorbate level (P<0.001) indicating damage of sperm cell surface, might be due to high membrane lipid peroxidation and failure of non-enzymatic antioxidant protection after lead exposure. Alteration of sperm membrane surface was also evidenced from scanning electron microscopy and further authenticated by atomic and lateral force microscopy. Lowering of sperm velocity, gross and forward progressive motility with high stationary motile spermatozoa (P<0.001) suggested retarded sperm activity among the exposed workers, which was supported by high seminal plasma fructose level and reduced activity of sperm ATPase (P < 0.001). Increased incidence of teratozoospermia was also associated with high blood and semen lead level (PbB, PbS) (P<0.001). Therefore, the results suggested that lead not only affects the sperm count, but also damages the sperm structure and membrane integrity, motility and functional activity among the battery and paint factory workers.

  10. 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.

  11. 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.

  12. Reconstructing ecosystem functions of the active microbial community of the Baltic Sea oxygen depleted sediments.

    PubMed

    Thureborn, Petter; 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

  13. 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

  14. CO assisted N2 functionalization activated by a dinuclear hafnium complex: a DFT mechanistic exploration.

    PubMed

    Ma, Xuelu; Zhang, Xin; Zhang, Wenchao; Lei, Ming

    2013-01-21

    In this paper, the reaction mechanisms of CO assisted N(2) cleavage and functionalization activated by a dinuclear hafnium complex are studied using a density function theory (DFT) method. Several key intermediates (Ia, Ib, Ic and Id) with axial/equatorial N=C=O coordination structures are found to be of importance along reaction pathways of CO assisted N(2) functionalization, which could provide a profound theoretical insight into the C-N bond formation and N-N bond cleavage. There are two different attack directions to insert the first CO molecule into the Hf-N bonds of the dinuclear hafnium complex, which lead to C-N bond formation. The calculated results imply that CO insertion into the Hf(1)-N(3) bond (Path A1) reacts more easily than that into the Hf(2)-N(3) bond (Path A3). But for the insertion of the second CO insertion to give 2A, there are two possibilities (Path A1 and Path A2) according to this insertion being after/before N-N bond cleavage. Two pathways (Path A1 and Path A2) are proved to be possible to form final dinitrogen functionalized products (oxamidide 2A, 2B and 2C) in this study, which explain the formation of different oxamidide isomers in CO assisted N(2) functionalization activated by a dinuclear hafnium complex.

  15. MicroRNA functionalized microporous titanium oxide surface by lyophilization with enhanced osteogenic activity.

    PubMed

    Wu, Kaimin; Song, Wen; Zhao, Lingzhou; Liu, Mengyuan; Yan, Jun; Andersen, Morten Østergaard; Kjems, Jørgen; Gao, Shan; Zhang, Yumei

    2013-04-10

    Developing biomedical titanium (Ti) implants with high osteogenic ability and consequent rigid osseointegration is a constant requirement from the clinic. In this study, we fabricate novel miRNA functionalized microporous Ti implants by lyophilizing miRNA lipoplexes onto a microporous titanium oxide surface formed by microarc oxidation (MAO). The microporous titanium oxide surface provides a larger surface area for miRNA loading and enables spatial retention of the miRNAs within the pores until cellular delivery. The loading of lipoplexes into the micropores on the MAO Ti surface is facilitated by the superhydrophilicity and Ti-OH groups gathering of the MAO surface after UV irradiation followed by lyophilization. A high miRNA transfection efficiency was observed in mesenchymal stem cells (MSCs) seeded onto the miRNA functionalized surface with no apparent cytotoxicity. When functionalizing the Ti surface with miR-29b that enhances osteogenic activity and antimiR-138 that inhibits miR-138 inhibition of endogenous osteogenesis, clear stimulation of MSC osteogenic differentiation was observed, in terms of up-regulating osteogenic expression and enhancing alkaline phosphatase production, collagen secretion and ECM mineralization. The novel miRNA functionalized Ti implants with enhanced osteogenic activity promisingly lead to more rapid and robust osseointegration of a clinical bone implant interface. Our study implies that lyophilization may constitute a versatile method for miRNA loading to other biomaterials with the aim of controlling cellular function. PMID:23459382

  16. 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

  17. 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.

  18. Interrogating Surface Functional Group Heterogeneity of Activated Thermoplastics Using Super-Resolution Fluorescence Microscopy.

    PubMed

    ONeil, Colleen E; Jackson, Joshua M; Shim, Sang-Hee; Soper, Steven A

    2016-04-01

    We present a novel approach for characterizing surfaces utilizing super-resolution fluorescence microscopy with subdiffraction limit spatial resolution. Thermoplastic surfaces were activated by UV/O3 or O2 plasma treatment under various conditions to generate pendant surface-confined carboxylic acids (-COOH). These surface functional groups were then labeled with a photoswitchable dye and interrogated using single-molecule, localization-based, super-resolution fluorescence microscopy to elucidate the surface heterogeneity of these functional groups across the activated surface. Data indicated nonuniform distributions of these functional groups for both COC and PMMA thermoplastics with the degree of heterogeneity being dose dependent. In addition, COC demonstrated relative higher surface density of functional groups compared to PMMA for both UV/O3 and O2 plasma treatment. The spatial distribution of -COOH groups secured from super-resolution imaging were used to simulate nonuniform patterns of electroosmotic flow in thermoplastic nanochannels. Simulations were compared to single-particle tracking of fluorescent nanoparticles within thermoplastic nanoslits to demonstrate the effects of surface functional group heterogeneity on the electrokinetic transport process.

  19. The orexin neuropeptide system: physical activity and hypothalamic function throughout the aging process

    PubMed Central

    Zink, Anastasia N.; Perez-Leighton, Claudio Esteban; Kotz, Catherine M.

    2014-01-01

    There is a rising medical need for novel therapeutic targets of physical activity. Physical activity spans from spontaneous, low intensity movements to voluntary, high-intensity exercise. Regulation of spontaneous and voluntary movement is distributed over many brain areas and neural substrates, but the specific cellular and molecular mechanisms responsible for mediating overall activity levels are not well understood. The hypothalamus plays a central role in the control of physical activity, which is executed through coordination of multiple signaling systems, including the orexin neuropeptides. Orexin producing neurons integrate physiological and metabolic information to coordinate multiple behavioral states and modulate physical activity in response to the environment. This review is organized around three questions: (1) How do orexin peptides modulate physical activity? (2) What are the effects of aging and lifestyle choices on physical activity? (3) What are the effects of aging on hypothalamic function and the orexin peptides? Discussion of these questions will provide a summary of the current state of knowledge regarding hypothalamic orexin regulation of physical activity during aging and provide a platform on which to develop improved clinical outcomes in age-associated obesity and metabolic syndromes. PMID:25408639

  20. Functional MRI of cerebellar activity during eyeblink classical conditioning in children and adults

    PubMed Central

    Cheng, Dominic T.; Meintjes, Ernesta M.; Stanton, Mark E.; Desmond, John E.; Pienaar, Mariska; Dodge, Neil C.; Power, John M.; Molteno, Christopher D.; Disterhoft, John F.; Jacobson, Joseph L.; Jacobson, Sandra W.

    2013-01-01

    This study characterized human cerebellar activity during eyeblink classical conditioning (EBC) in children and adults using functional magnetic resonance imaging (fMRI). During fMRI, participants were administered delay conditioning trials, in which the conditioned stimulus (a tone) precedes, overlaps, and coterminates with the unconditioned stimulus (a corneal airpuff). Behavioral eyeblink responses and brain activation were measured concurrently during two phases: pseudoconditioning, involving presentations of tone alone and airpuff alone, and conditioning, during which the tone and airpuff were paired. Although all participants demonstrated significant conditioning, the adults produced more conditioned responses (CRs) than the children. When brain activations during pseudoconditioning were subtracted from those elicited during conditioning, significant activity was distributed throughout the cerebellar cortex (Crus I– II, lateral lobules IV–IX, and vermis IV–VI) in all participants, suggesting multiple sites of associative learning-related plasticity. Despite their less optimal behavioral performance, the children showed greater responding in the pons, lateral lobules VIII, IX, and Crus I, and vermis VI, suggesting that they may require greater activation and/or the recruitment of supplementary structures to achieve successful conditioning. Correlation analyses relating brain activations to behavioral CRs showed a positive association of activity in cerebellar deep nuclei (including dentate, fastigial, and interposed nuclei) and vermis VI with CRs in the children. This is the first study to compare cerebellar cortical and deep nuclei activations in children versus adults during eyeblink classical conditioning. PMID:23674498

  1. Functional MRI of cerebellar activity during eyeblink classical conditioning in children and adults.

    PubMed

    Cheng, Dominic T; Meintjes, Ernesta M; Stanton, Mark E; Desmond, John E; Pienaar, Mariska; Dodge, Neil C; Power, John M; Molteno, Christopher D; Disterhoft, John F; Jacobson, Joseph L; Jacobson, Sandra W

    2014-04-01

    This study characterized human cerebellar activity during eyeblink classical conditioning (EBC) in children and adults using functional magnetic resonance imaging (fMRI). During fMRI, participants were administered delay conditioning trials, in which the conditioned stimulus (a tone) precedes, overlaps, and coterminates with the unconditioned stimulus (a corneal airpuff). Behavioral eyeblink responses and brain activation were measured concurrently during two phases: pseudoconditioning, involving presentations of tone alone and airpuff alone, and conditioning, during which the tone and airpuff were paired. Although all participants demonstrated significant conditioning, the adults produced more conditioned responses (CRs) than the children. When brain activations during pseudoconditioning were subtracted from those elicited during conditioning, significant activity was distributed throughout the cerebellar cortex (Crus I-II, lateral lobules IV-IX, and vermis IV-VI) in all participants, suggesting multiple sites of associative learning-related plasticity. Despite their less optimal behavioral performance, the children showed greater responding in the pons, lateral lobules VIII, IX, and Crus I, and vermis VI, suggesting that they may require greater activation and/or the recruitment of supplementary structures to achieve successful conditioning. Correlation analyses relating brain activations to behavioral CRs showed a positive association of activity in cerebellar deep nuclei (including dentate, fastigial, and interposed nuclei) and vermis VI with CRs in the children. This is the first study to compare cerebellar cortical and deep nuclei activations in children versus adults during EBC.

  2. Sequential muscle activity and its functional role in the upper extremity and trunk during overarm throwing.

    PubMed

    Hirashima, Masaya; Kadota, Hiroshi; Sakurai, Shizuka; Kudo, Katzutoshi; Ohtsuki, Tatsuyuki

    2002-04-01

    The proximal-to-distal segmental sequence has been identified in many sports activities, including baseball pitching and ball kicking. However, proximal-to-distal sequential muscle activity has not been identified. The aims of this study were to establish whether sequential muscle activity does occur and, if it does, to determine its functional role. We recorded surface electromyograms (EMGs) for 17 muscles from the upper extremity and abdomen during overarm throwing and detected the onset and peak times as indices of muscle activity. The following electromyographic properties were commonly identified in the participants. First, sequential muscle activity was observed from the scapular protractors to the shoulder horizontal flexors and from the shoulder horizontal flexors to the elbow extensor, but not from the elbow extensor to the wrist flexor or forearm pronator. Secondly, the external oblique contralateral to the throwing arm became activated before the ipsilateral external oblique. This sequence is considered to be very effective for the generation of high force and energy in the trunk. Thirdly, the ipsilateral external oblique began its activity almost at foot strike. Finally, the main activity of the rectus abdominis appeared just before the point of release.

  3. Functional neuronal network activity differs with cognitive dysfunction in childhood-onset systemic lupus erythematosus

    PubMed Central

    2013-01-01

    Introduction Neuropsychiatric manifestations are common in childhood-onset systemic lupus erythematosus (cSLE) and often include neurocognitive dysfunction (NCD). Functional magnetic resonance imaging (fMRI) can measure brain activation during tasks that invoke domains of cognitive function impaired by cSLE. This study investigates specific changes in brain function attributable to NCD in cSLE that have potential to serve as imaging biomarkers. Methods Formal neuropsychological testing was done to measure cognitive ability and to identify NCD. Participants performed fMRI tasks probing three cognitive domains impacted by cSLE: visuoconstructional ability (VCA), working memory, and attention. Imaging data, collected on 3-Tesla scanners, included a high-resolution T1-weighted anatomic reference image followed by a T2*-weighted whole-brain echo planar image series for each fMRI task. Brain activation using blood oxygenation level-dependent contrast was compared between cSLE patients with NCD (NCD-group, n = 7) vs. without NCD (noNCD-group, n = 14) using voxel-wise and region of interest-based analyses. The relationship of brain activation during fMRI tasks and performance in formal neuropsychological testing was assessed. Results Greater brain activation was observed in the noNCD-group vs. NCD-group during VCA and working memory fMRI tasks. Conversely, compared to the noNCD-group, the NCD-group showed more brain activation during the attention fMRI task. In region of interest analysis, brain activity during VCA and working memory fMRI tasks was positively associated with the participants' neuropsychological test performance. In contrast, brain activation during the attention fMRI task was negatively correlated with neuropsychological test performance. While the NCD group performed worse than the noNCD group during VCA and working memory tasks, the attention task was performed equally well by both groups. Conclusions NCD in patients with cSLE is characterized by

  4. 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

  5. Electrochemical assay of active prostate-specific antigen (PSA) using ferrocene-functionalized peptide probes

    SciTech Connect

    Zhao, Ning; He, Yuqing; Mao, Xun; Sun, Yuhan; Zhang, Xibao; Li, Chen-Zhong; Lin, Yuehe; Liu, Guodong

    2010-03-24

    This paper presents a novel approach to electrochemically determine enzymatically active PSA using ferrocene-functionalized helix peptide (CHSSLKQK). The principle of electrochemical measurement is based on the specific proteolytic cleavage events of the FC-peptide on the gold electrode surface in the presence of PSA, resulting the change of the current signal of the electrode. The percentage of the decreased current is linear with the concentration of active PSA at the range of 0.5-40 ng/mL with a detection limit of 0.2 ng/mL. The direct transduction of peptide cleavage events into an electrical signal provides a simple, sensitive method for detecting the enzymatic activity of PSA and determining the active PSA concentration.

  6. Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function.

    PubMed

    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

    2015-10-16

    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.

  7. 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.

  8. Pharmacological Activation of Thyroid Hormone Receptors Elicits a Functional Conversion of White to Brown Fat.

    PubMed

    Lin, Jean Z; Martagón, Alexandro J; Cimini, Stephanie L; Gonzalez, Daniel D; Tinkey, David W; Biter, Amadeo; Baxter, John D; Webb, Paul; Gustafsson, Jan-Åke; Hartig, Sean M; Phillips, Kevin J

    2015-11-24

    The functional conversion of white adipose tissue (WAT) into a tissue with brown adipose tissue (BAT)-like activity, often referred to as "browning," represents an intriguing strategy for combating obesity and metabolic disease. We demonstrate that thyroid hormone receptor (TR) activation by a synthetic agonist markedly induces a program of adaptive thermogenesis in subcutaneous WAT that coincides with a restoration of cold tolerance to cold-intolerant mice. Distinct from most other browning agents, pharmacological TR activation dissociates the browning of WAT from activation of classical BAT. TR agonism also induces the browning of white adipocytes in vitro, indicating that TR-mediated browning is cell autonomous. These data establish TR agonists as a class of browning agents, implicate the TRs in the browning of WAT, and suggest a profound pharmacological potential of this action.

  9. 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

  10. Mining functional relationships in feature subspaces from gene expression profiles and drug activity profiles.

    PubMed

    Bao, Lei; Guo, Tao; Sun, Zhirong

    2002-04-10

    In an effort to determine putative functional relationships between gene expression patterns and drug activity patterns of 60 human cancer cell lines, a novel method was developed to discover local associations within cell line subsets. The association of drug-gene pairs is an explorative way of discovering gene markers that predict clinical tumor sensitivity to therapy. Nine drug-gene networks were discovered, as well as dozens of gene-gene and drug-drug networks. Three drug-gene networks with well studied members were discussed and the literature shows that hypothetical functional relationships exist. Therefore, this method enables the gathering of new information beyond global associations.

  11. Influenza matrix protein 2 alters CFTR expression and function through its ion channel activity.

    PubMed

    Londino, James D; Lazrak, Ahmed; Jurkuvenaite, Asta; Collawn, James F; Noah, James W; Matalon, Sadis

    2013-05-01

    The human cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-activated chloride (Cl(-)) channel in the lung epithelium that helps regulate the thickness and composition of the lung epithelial lining fluid. We investigated whether influenza M2 protein, a pH-activated proton (H(+)) channel that traffics to the plasma membrane of infected cells, altered CFTR expression and function. M2 decreased CFTR activity in 1) Xenopus oocytes injected with human CFTR, 2) epithelial cells (HEK-293) stably transfected with CFTR, and 3) human bronchial epithelial cells (16HBE14o-) expressing native CFTR. This inhibition was partially reversed by an inhibitor of the ubiquitin-activating enzyme E1. Next we investigated whether the M2 inhibition of CFTR activity was due to an increase of secretory organelle pH by M2. Incubation of Xenopus oocytes expressing CFTR with ammonium chloride or concanamycin A, two agents that alkalinize the secretory pathway, inhibited CFTR activity in a dose-dependent manner. Treatment of M2- and CFTR-expressing oocytes with the M2 ion channel inhibitor amantadine prevented the loss in CFTR expression and activity; in addition, M2 mutants, lacking the ability to transport H(+), did not alter CFTR activity in Xenopus oocytes and HEK cells. Expression of an M2 mutant retained in the endoplasmic reticulum also failed to alter CFTR activity. In summary, our data show that M2 decreases CFTR activity by increasing secretory organelle pH, which targets CFTR for destruction by the ubiquitin system. Alteration of CFTR activity has important consequences for fluid regulation and may potentially modify the immune response to viral infection.

  12. Influenza matrix protein 2 alters CFTR expression and function through its ion channel activity

    PubMed Central

    Londino, James D.; Lazrak, Ahmed; Jurkuvenaite, Asta; Collawn, James F.; Noah, James W.

    2013-01-01

    The human cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-activated chloride (Cl−) channel in the lung epithelium that helps regulate the thickness and composition of the lung epithelial lining fluid. We investigated whether influenza M2 protein, a pH-activated proton (H+) channel that traffics to the plasma membrane of infected cells, altered CFTR expression and function. M2 decreased CFTR activity in 1) Xenopus oocytes injected with human CFTR, 2) epithelial cells (HEK-293) stably transfected with CFTR, and 3) human bronchial epithelial cells (16HBE14o−) expressing native CFTR. This inhibition was partially reversed by an inhibitor of the ubiquitin-activating enzyme E1. Next we investigated whether the M2 inhibition of CFTR activity was due to an increase of secretory organelle pH by M2. Incubation of Xenopus oocytes expressing CFTR with ammonium chloride or concanamycin A, two agents that alkalinize the secretory pathway, inhibited CFTR activity in a dose-dependent manner. Treatment of M2- and CFTR-expressing oocytes with the M2 ion channel inhibitor amantadine prevented the loss in CFTR expression and activity; in addition, M2 mutants, lacking the ability to transport H+, did not alter CFTR activity in Xenopus oocytes and HEK cells. Expression of an M2 mutant retained in the endoplasmic reticulum also failed to alter CFTR activity. In summary, our data show that M2 decreases CFTR activity by increasing secretory organelle pH, which targets CFTR for destruction by the ubiquitin system. Alteration of CFTR activity has important consequences for fluid regulation and may potentially modify the immune response to viral infection. PMID:23457187

  13. 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. PMID:24731451

  14. 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.

  15. 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

  16. 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

  17. Associations of Monitor-Assessed Activity with Performance-Based Physical Function.

    PubMed

    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

  18. The calcium-activated chloride channel Anoctamin 1 contributes to the regulation of renal function.

    PubMed

    Faria, Diana; Rock, Jason R; Romao, Ana M; Schweda, Frank; Bandulik, Sascha; Witzgall, Ralph; Schlatter, Eberhard; Heitzmann, Dirk; Pavenstädt, Hermann; Herrmann, Edwin; Kunzelmann, Karl; Schreiber, Rainer

    2014-06-01

    The role of calcium-activated chloride channels for renal function is unknown. By immunohistochemistry we demonstrate dominant expression of the recently identified calcium-activated chloride channels, Anoctamin 1 (Ano1, TMEM16A) in human and mouse proximal tubular epithelial (PTE) cells, with some expression in podocytes and other tubular segments. Ano1-null mice had proteinuria and numerous large reabsorption vesicles in PTE cells. Selective knockout of Ano1 in podocytes (Ano1-/-/Nphs2-Cre) did not impair renal function, whereas tubular knockout in Ano1-/-/Ksp-Cre mice increased urine protein excretion and decreased urine electrolyte concentrations. Purinergic stimulation activated calcium-dependent chloride currents in isolated proximal tubule epithelial cells from wild-type but not from Ano1-/-/Ksp-Cre mice. Ano1 currents were activated by acidic pH, suggesting parallel stimulation of Ano1 chloride secretion with activation of the proton-ATPase. Lack of calcium-dependent chloride secretion in cells from Ano1-/-/Ksp-Cre mice was paralleled by attenuated proton secretion and reduced endosomal acidification, which compromised proximal tubular albumin uptake. Tubular knockout of Ano1 enhanced serum renin and aldosterone concentrations, probably leading to enhanced compensatory distal tubular reabsorption, thus maintaining normal blood pressure levels. Thus, Ano1 has a role in proximal tubular proton secretion and protein reabsorption. The results correspond to regulation of the proton-ATPase by the Ano1-homolog Ist2 in yeast.

  19. 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

  20. [Effect of physical activity on age involution of functional abilities of humans].

    PubMed

    Miskotnykh, V V; Khodasevich, L S; Mel'tser, V L

    2012-01-01

    A survey of 433 healthy, mature- and middle-aged men with different modes of habitual daily physical activity was made. Depending on the modes of motor activity all the surveyed were divided into 4 groups, each of which has been ranked by the ten-year age interval. The assessment of functional status using automated hardware-software complex "AMSAT-Covert" to determine the level of maximum oxygen consumption, lipid peroxidation and activity of the antioxidant defense system was performed. Results of the study enabled the authors to formulate a provision under which to extend the period of active, creative longevity and increased life expectancy we need to review the approaches to the regulation of physical activity by rationally constructed motor mode as part of a comprehensive system of health protection. Exercises, not increasing the requirements to the functionality involved and not causing physiological changes should be included in the recommended motor mode, which are incomparably less than officially accepted in modern practice fitness training.

  1. Effects of polybrominated biphenyls on kidney function and activity of renal microsomal enzymes.

    PubMed

    McCormack, K M; Kluwe, W M; Sanger, V L; Hook, J B

    1978-04-01

    Polybrominated biphenyls (PBBs) cause hepatic microsomal enzyme stimulation and histopathological alterations in several organs, including kidney. Concern about effects of PBBs on the health of newborns has increased after the discovery of PBBs in milk of nursing mothers. Therefore, it was of interest to investigate the effects of PBBs on kidney function and the activity of renal microsomal enzymes in adult and immature animals. Seven and eleven day old pups were treated with a single IP injection of either peanut oil or 150 mg/kg PBBs (FireMaster BP-6) in peanut oil. Adult virgin rats were fed diet containing 0 or 100 ppm PBBs for 30 or 90 days. Treatment with PBBs only retarded weight gain after 90 days exposure. Kidney-to-body weight ratio was not altered by PBBs. Arylhydrocarbon hydroxylase activity was increased while epoxide hydratase activity was decreased (adults) or not affected (immature rats) in kidney following treatment with PBBs. Administration of PBBs had no effect on blood urea nitrogen, the clearance of inulin, p-aminohippurate (PAH), or fractional sodium excretion. Similarly, the in vitro accumulation of PAH and N-methylnicotinamide (NMN) by thin renal cortical slices and ammoniagenesis and gluconeogenesis in renal cortical slices were not affected by PBBs. In conclusion, treatment with PBBs resulted in modification of the activity of renal microsomal enzyme activities but had no detectable effect on renal function. PMID:209969

  2. 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.

  3. Robust stability analysis of delayed Takagi-Sugeno fuzzy Hopfield neural networks with discontinuous activation functions

    PubMed Central

    Huang, Lihong; Zuo, Yi

    2010-01-01

    In this paper, the global robust stability problem of delayed Takagi–Sugeno fuzzy Hopfield neural networks with discontinuous activation functions (TSFHNNs) is considered. Based on Lyapunov stability theory and M-matrices theory, we derive a stability criterion to guarantee the global robust stability of TSFHNNs. Compared with the existing literature, we remove the assumptions on the neuron activations such as Lipschitz conditions, bounded, monotonic increasing property or the assumption that the right-limit value is bigger than the left one at the discontinuous point. Finally, two numerical examples are given to show the effectiveness of the proposed stability results. PMID:22132043

  4. 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

    2014-05-01

    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.

  5. High PLTP activity is associated with depressed left ventricular systolic function.

    PubMed

    Chen, Xueying; Sun, Aijun; Zou, Yunzeng; Ge, Junbo; Kamran, Haroon; Jiang, Xian-Cheng; Lazar, Jason M

    2013-06-01

    Phospholipid transfer protein (PLTP) modulates lipoprotein metabolism and plays an important role in inflammation and oxidative stress. High PLTP activity is associated with atherosclerosis and its risk factors, which also predispose to left ventricular systolic (LV) dysfunction and/or congestive heart failure. However there are few data linking PLTP activity directly to LV function. According, we sought to determine the relation between PLTP activity and LV ejection fraction (EF) in a Chinese cohort of 732 patients referred for coronary angiography. Weak but significant correlations of PLTP activity levels were found with age (r = -0.09, p = 0.017), male gender (r = 0.09, p = 0.019), diabetes (r = 0.08, p = 0.036), TG (r = 0.11, p = 0.003), HDL-C (r = -0.18, p = <0.001), apo A (-0.30, p < 0.001) apo B (r = 0.20, p < 0.001), fibrinogen (r = 0.32, p < 0.001) and LVEF (r = -0.12, p = 0.003). Median PLTP activity levels were higher among patients with reduced than in normal LV systolic function (LVEF <50%) [26.7 pmol/microl/h (IQR 20.2, 38.6) vs. 19.9 pmol/microl/h (IQR 12.2, 31.0), p < 0.001]. There was a step-wise increase in median PLTP levels in patients with normal, mild, and moderate-severe degrees of LV dysfunction (19.9 pmol/microl/h vs. 25.1 pmol/microl/h vs. 34.7 pmol/microl/h, p < 0.001). Median PLTP activity levels were higher among patients with unstable rather than stable AP and non-CHD patients (25.9 pmol/microl/h vs 20.2 vs 21.9, p = 0.012). On multivariate analyzes, higher median PLTP activity levels were associated with depressed LV systolic function as a dichotomous variable and with lower LVEF as a continuous variable. In conclusion, higher PLTP activity is associated with depressed LV systolic function in a dose-dependent manner independent of coronary heart disease as well as to unstable CHD.

  6. The associations of physical activity and television watching with change in kidney function in older adults

    PubMed Central

    Hawkins, Marquis; Newman, Anne B.; Madero, Magdalena; Patel, Kushang V.; Shlipak, Michael G.; Cooper, Jennifer; Johansen, Kirsten L.; Navaneethan, Sankar D.; Fried, Linda F

    2015-01-01

    BACKGROUND Physical activity (PA) may play a role in preserving kidney health. The purpose of this study was to determine if PA and sedentary behavior are associated with incident chronic kidney disease (CKD) and change in kidney function in older adults. METHODS The Health, Aging and Body Composition study is a prospective cohort of 3,075 well-functioning older adults. PA and television watching was measured by self-report and serum cystatin C was used to estimate glomerular filtration rate (eGFR). CKD was defined as an eGFR <60 ml/min/1.73m2. Rapid kidney function decline was defined as an annual loss in eGFR of >3ml/min/1.73m2. Discrete survival analysis was used to determine if baseline PA and television watching were related to 10-year cumulative incidence of CKD and rapid decline in kidney function. RESULTS Individuals who reported watching television >3 hours/day had a higher risk of incident CKD (HR 1.34; 95% CI: 1.09, 1.65) and experiencing a rapid decline in kidney function (HR 1.26; 95% CI 1.05, 1.52) compared to individuals who watched television < 2 hours/day. PA was not related to either outcome. CONCLUSIONS High levels of television watching are associated with declining kidney function; the mechanisms that underlie this association need further study. PMID:24762526

  7. Revealing microbial functional activities in the Red Sea sponge Stylissa carteri by metatranscriptomics.

    PubMed

    Moitinho-Silva, Lucas; Seridi, Loqmane; Ryu, Taewoo; Voolstra, Christian R; Ravasi, Timothy; Hentschel, Ute

    2014-12-01

    Sponges are important components of marine benthic environments and are associated with microbial symbionts that carry out ecologically relevant functions. Stylissa carteri is an abundant, low-microbial abundance species in the Red Sea. We aimed to achieve the functional and taxonomic characterization of the most actively expressed prokaryotic genes in S. carteri. Prokaryotic mRNA was enriched from sponge total RNA, sequenced using Illumina HiSeq technology and annotated using the metagenomics Rapid Annotation using Subsystem Technology (MG-RAST) pipeline. We detected high expression of archaeal ammonia oxidation and photosynthetic carbon fixation by members of the genus Synechococcus. Functions related to stress response and membrane transporters were among the most highly expressed by S. carteri symbionts. Unexpectedly, gene functions related to methylotrophy were highly expressed by gammaproteobacterial symbionts. The presence of seawater-derived microbes is indicated by the phylogenetic proximity of organic carbon transporters to orthologues of members from the SAR11 clade. In summary, we revealed the most expressed functions of the S. carteri-associated microbial community and linked them to the dominant taxonomic members of the microbiome. This work demonstrates the applicability of metatranscriptomics to explore poorly characterized symbiotic consortia and expands our knowledge of the ecologically relevant functions carried out by coral reef sponge symbionts.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. CAST and ELKS proteins: structural and functional determinants of the presynaptic active zone.

    PubMed

    Hida, Yamato; Ohtsuka, Toshihisa

    2010-08-01

    Cytomatrix at the active zone-associated structural protein (CAST) was first purified from rat brain. It belongs to a protein family with the protein ELKS being its close relative. In nerve terminals, these proteins are specifically localized in the active zone (AZ). They have been shown to directly interact with other AZ proteins, including RIM1, Piccolo and Bassoon, and indirectly with Munc13-1 through RIM1, forming a large molecular complex at AZ. Moreover, the direct interaction of CAST with RIM1 and Bassoon appears to be involved in the release of neurotransmitters. However, it still remains elusive how CAST and ELKS regulate the assembly and function of AZ during synapse maturation. This review focuses on recent findings about the ELKS/CAST family revealed by biochemical strategies and genetic studies, and discusses the potential roles of this protein family in the function and organization of the presynaptic AZ.

  13. 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.

  14. ALD functionalized nanoporous gold: thermal stability, mechanical properties, and catalytic activity.

    PubMed

    Biener, Monika M; Biener, Juergen; Wichmann, Andre; Wittstock, Arne; Baumann, Theodore F; Bäumer, Marcus; Hamza, Alex V

    2011-08-10

    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 1 nm thick oxide films can stabilize the nanoscale morphology of np-Au up to 1,000°C, while simultaneously making the material stronger and stiffer. The catalytic activity of np-Au can be drastically increased by TiO(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.

  15. Olfactory stimulatory with grapefruit and lavender oils change autonomic nerve activity and physiological function.

    PubMed

    Nagai, Katsuya; Niijima, Akira; Horii, Yuko; Shen, Jiao; Tanida, Mamoru

    2014-10-01

    This review summarizes the effects of olfactory stimulation with grapefruit and lavender oils on autonomic nerve activity and physiological function. Olfactory stimulation with the scent of grapefruit oil (GFO) increases the activity of sympathetic nerves that innervate white and brown adipose tissues, the adrenal glands, and the kidneys, decreases the activity of the gastric vagal nerve in rats and mice. This results in an increase in lipolysis, thermogenesis, and blood pressure, and a decrease in food intake. Olfactory stimulation with the scent of lavender oil (LVO) elicits the opposite changes in nerve activity and physiological variables. Olfactory stimulation with scent of limonene, a component of GFO, and linalool, a component of LVO, has similar effects to stimulation with GFO and LVO, respectively. The histamine H1-receptor antagonist, diphenhydramine, abolishes all GFO-induced changes in nerve activity and physiological variables, and the hitstamine H3-receptor antagonist, thioperamide, eliminates all LVO-induced changes. Lesions to the hypothalamic suprachiasmatic nucleus and anosmic treatment with ZnSO4 also abolish all GFO- and LVO-induced changes. These findings indicate that limonene and linalool might be the active substances in GFO and LVO, and suggest that the suprachiasmatic nucleus and histamine are involved in mediating the GFO- and LVO-induced changes in nerve activity and physiological variables. PMID:25002406

  16. Functional reconstitution and channel activity measurements of purified wildtype and mutant CFTR protein.

    PubMed

    Eckford, Paul D W; Li, Canhui; Bear, Christine E

    2015-03-09

    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.

  17. Type I interferons produced by dendritic cells promote their phenotypic and functional activation.

    PubMed

    Montoya, Maria; Schiavoni, Giovanna; Mattei, Fabrizio; Gresser, Ion; Belardelli, Filippo; Borrow, Persephone; Tough, David F

    2002-05-01

    Resting dendritic cells (DCs) are resident in most tissues and can be activated by environmental stimuli to mature into potent antigen-presenting cells. One important stimulus for DC activation is infection; DCs can be triggered through receptors that recognize microbial components directly or by contact with infection-induced cytokines. We show here that murine DCs undergo phenotypic maturation upon exposure to type I interferons (type I IFNs) in vivo or in vitro. Moreover, DCs either derived from bone marrow cells in vitro or isolated from the spleens of normal animals express IFN-alpha and IFN-beta, suggesting that type I IFNs can act in an autocrine manner to activate DCs. Consistent with this idea, the ability to respond to type I IFN was required for the generation of fully activated DCs from bone marrow precursors, as DCs derived from the bone marrow of mice lacking a functional receptor for type I IFN had reduced expression of costimulatory and adhesion molecules and a diminished ability to stimulate naive T-cell proliferation compared with DCs derived from control bone marrow. Furthermore, the addition of neutralizing anti-IFN-alpha/beta antibody to purified splenic DCs in vitro partially blocked the "spontaneous" activation of these cells, inhibiting the up-regulation of costimulatory molecules, secretion of IFN-gamma, and T-cell stimulatory activity. These results show that DCs both secrete and respond to type I IFN, identifying type I interferons as autocrine DC activators. PMID:11964292

  18. Spontaneous brain activity observed with functional magnetic resonance imaging as a potential biomarker in neuropsychiatric disorders

    PubMed Central

    Zhou, Yuan; Wang, Kun; Liu, Yong; Song, Ming; Song, Sonya W.

    2010-01-01

    As functional magnetic resonance imaging (fMRI) studies have yielded increasing amounts of information about the brain’s spontaneous activity, they have revealed fMRI’s potential to locate changes in brain hemodynamics that are associated with neuropsychiatric disorders. In this paper, we review studies that support the notion that changes in brain spontaneous activity observed by fMRI can be used as potential biomarkers for diagnosis and treatment evaluation in neuropsychiatric disorders. We first review the methods used to study spontaneous activity from the perspectives of (1) the properties of local spontaneous activity, (2) the spatial pattern of spontaneous activity, and (3) the topological properties of brain networks. We also summarize the major findings associated with major neuropsychiatric disorders obtained using these methods. Then we review the pilot studies that have used spontaneous activity to discriminate patients from normal controls. Finally, we discuss current challenges and potential research directions to further elucidate the clinical use of spontaneous brain activity in neuropsychiatric disorders. PMID:22132039

  19. Olfactory stimulatory with grapefruit and lavender oils change autonomic nerve activity and physiological function.

    PubMed

    Nagai, Katsuya; Niijima, Akira; Horii, Yuko; Shen, Jiao; Tanida, Mamoru

    2014-10-01

    This review summarizes the effects of olfactory stimulation with grapefruit and lavender oils on autonomic nerve activity and physiological function. Olfactory stimulation with the scent of grapefruit oil (GFO) increases the activity of sympathetic nerves that innervate white and brown adipose tissues, the adrenal glands, and the kidneys, decreases the activity of the gastric vagal nerve in rats and mice. This results in an increase in lipolysis, thermogenesis, and blood pressure, and a decrease in food intake. Olfactory stimulation with the scent of lavender oil (LVO) elicits the opposite changes in nerve activity and physiological variables. Olfactory stimulation with scent of limonene, a component of GFO, and linalool, a component of LVO, has similar effects to stimulation with GFO and LVO, respectively. The histamine H1-receptor antagonist, diphenhydramine, abolishes all GFO-induced changes in nerve activity and physiological variables, and the hitstamine H3-receptor antagonist, thioperamide, eliminates all LVO-induced changes. Lesions to the hypothalamic suprachiasmatic nucleus and anosmic treatment with ZnSO4 also abolish all GFO- and LVO-induced changes. These findings indicate that limonene and linalool might be the active substances in GFO and LVO, and suggest that the suprachiasmatic nucleus and histamine are involved in mediating the GFO- and LVO-induced changes in nerve activity and physiological variables.

  20. Atypical activation during the Embedded Figures Task as a functional magnetic resonance imaging endophenotype of autism.

    PubMed

    Spencer, Michael D; Holt, Rosemary J; Chura, Lindsay R; Calder, Andrew J; Suckling, John; Bullmore, Edward T; Baron-Cohen, Simon

    2012-11-01

    Atypical activation during the Embedded Figures Task has been demonstrated in autism, but has not been investigated in siblings or related to measures of clinical severity. We identified atypical activation during the Embedded Figures Task in participants with autism and unaffected siblings compared with control subjects in a number of temporal and frontal brain regions. Autism and sibling groups, however, did not differ in terms of activation during this task. This suggests that the pattern of atypical activation identified may represent a functional endophenotype of autism, related to familial risk for the condition shared between individuals with autism and their siblings. We also found that reduced activation in autism relative to control subjects in regions including associative visual and face processing areas was strongly correlated with the clinical severity of impairments in reciprocal social interaction. Behavioural performance was intact in autism and sibling groups. Results are discussed in terms of atypical information processing styles or of increased activation in temporal and frontal regions in autism and the broader phenotype. By separating the aspects of atypical activation as markers of familial risk for the condition from those that are autism-specific, our findings offer new insight into the factors that might cause the expression of autism in families, affecting some children but not others.

  1. Functional Mapping of Protein Kinase A Reveals Its Importance in Adult Schistosoma mansoni Motor Activity

    PubMed Central

    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

  2. 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.

  3. Adsorption and destruction of PCDD/Fs using surface-functionalized activated carbons.

    PubMed

    Atkinson, J D; Hung, P C; Zhang, Z; Chang, M B; Yan, Z; Rood, M J

    2015-01-01

    Activated carbon adsorbs polychlorinated dibenzo-p-dioxins and -furans (PCDD/Fs) from gas streams but can simultaneously generate PCDD/Fs via de novo synthesis, increasing an already serious disposal problem for the spent sorbent. To increase activated carbon's PCDD/F sorption capacity and lifetime while reducing the impact of hazardous waste, it is beneficial to develop carbon-based sorbents that simultaneously destroy PCDD/Fs while adsorbing the toxic chemicals from gas streams. In this work, hydrogen-treated and surface-functionalized (i.e., oxygen, bromine, nitrogen, and sulfur) activated carbons are tested in a bench-scale reactor as adsorbents for PCDD/Fs. All tested carbons adsorb PCDD/F efficiently, with international toxic equivalent removal efficiencies exceeding 99% and mass removal efficiencies exceeding 98% for all but one tested material. Hydrogen-treated materials caused negligible destruction and possible generation of PCDD/Fs, with total mass balances between 100% and 107%. All tested surface-functionalized carbons, regardless of functionality, destroyed PCDD/Fs, with total mass balances between 73% and 96%. Free radicals on the carbon surface provided by different functional groups may contribute to PCDD/F destruction, as has been hypothesized in the literature. Surface-functionalized materials preferentially destroyed higher-order (more chlorine) congeners, supporting a dechlorination mechanism as opposed to oxidation. Carbons impregnated with sulfur are particularly effective at destroying PCDD/Fs, with destruction efficiency improving with increasing sulfur content to as high as 27%. This is relevant because sulfur-treated carbons are used for mercury adsorption, increasing the possibility of multi-pollutant control.

  4. The Activating Transcription Factor 3 Protein Suppresses the Oncogenic Function of Mutant p53 Proteins*

    PubMed Central

    Wei, Saisai; Wang, Hongbo; Lu, Chunwan; Malmut, Sarah; Zhang, Jianqiao; Ren, Shumei; Yu, Guohua; Wang, Wei; Tang, Dale D.; Yan, Chunhong

    2014-01-01

    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. PMID:24554706

  5. 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

  6. Participation of functionally active plasma cells in acute rejection and response to therapy in renal allografts.

    PubMed

    Bhat, Zeenat Yousuf; Bostwick, David G; Hossain, Deloar; Zeng, Xu

    2014-07-01

    Acute rejection (AR) includes T-cell-mediated and antibody-mediated rejection. The inflammatory infiltrate comprised not only T cells but also varying amounts of B cells (CD20(+)) and plasma cells (CD138(+)). The latter are associated with poor clinical outcomes, but their functional status is not clear. The phosphorylation of the S6 ribosomal protein (p-S6RP) is present in cells that are metabolically active, thus identifying functionally active antibody-secreting plasma cells. This study was designed to evaluate the clinical significance of functionally active p-S6RP plasma cells in AR in renal allografts. Renal allografts with biopsy evidence of AR during 2006-2009 were included. Immunohistochemistry staining for CD20, CD138, and p-S6RP was performed on paraffin-embedded slides and scaled as 0-6. The response to antirejection treatment was assessed by the serum creatinine ratio (CrR) at rejection episode (time 0) and following treatment (4 and 12 weeks). Patients with lower scores (0-2) were compared with a higher scored group (3-6). The T-test was conducted using statistical significance of p<0.05. A total of 28 patients (40.7 ± 14.3 year; M:F=15:13) were diagnosed with acute T-cell-mediated rejection (I and II). The p-S6RP staining in the high-score group had a significantly higher CrR (p<0.05) than the low-score group at the time of biopsy, 4 and 12 weeks following treatment. There was no significant difference in the CrR between groups for CD20 or CD138 staining. Functional antibody-secreting p-S6RP plasma cells are actively participating in AR and associated with poor response to treatment in renal allografts. PMID:24684655

  7. 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

  8. Tools for resolving functional activity and connectivity within intact neural circuits.

    PubMed

    Jennings, Joshua H; Stuber, Garret D

    2014-01-01

    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.

  9. 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.

  10. 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.

  11. Extensive site-directed mutagenesis reveals interconnected functional units in the alkaline phosphatase active site.

    PubMed

    Sunden, Fanny; Peck, Ariana; Salzman, Julia; Ressl, Susanne; Herschlag, Daniel

    2015-01-01

    Enzymes enable life by accelerating reaction rates to biological timescales. Conventional studies have focused on identifying the residues that have a direct involvement in an enzymatic reaction, but these so-called 'catalytic residues' are embedded in extensive interaction networks. Although fundamental to our understanding of enzyme function, evolution, and engineering, the properties of these networks have yet to be quantitatively and systematically explored. We dissected an interaction network of five residues in the active site of Escherichia coli alkaline phosphatase. Analysis of the complex catalytic interdependence of specific residues identified three energetically independent but structurally interconnected functional units with distinct modes of cooperativity. From an evolutionary perspective, this network is orders of magnitude more probable to arise than a fully cooperative network. From a functional perspective, new catalytic insights emerge. Further, such comprehensive energetic characterization will be necessary to benchmark the algorithms required to rationally engineer highly efficient enzymes. PMID:25902402

  12. Extensive site-directed mutagenesis reveals interconnected functional units in the alkaline phosphatase active site.

    PubMed

    Sunden, Fanny; Peck, Ariana; Salzman, Julia; Ressl, Susanne; Herschlag, Daniel

    2015-01-01

    Enzymes enable life by accelerating reaction rates to biological timescales. Conventional studies have focused on identifying the residues that have a direct involvement in an enzymatic reaction, but these so-called 'catalytic residues' are embedded in extensive interaction networks. Although fundamental to our understanding of enzyme function, evolution, and engineering, the properties of these networks have yet to be quantitatively and systematically explored. We dissected an interaction network of five residues in the active site of Escherichia coli alkaline phosphatase. Analysis of the complex catalytic interdependence of specific residues identified three energetically independent but structurally interconnected functional units with distinct modes of cooperativity. From an evolutionary perspective, this network is orders of magnitude more probable to arise than a fully cooperative network. From a functional perspective, new catalytic insights emerge. Further, such comprehensive energetic characterization will be necessary to benchmark the algorithms required to rationally engineer highly efficient enzymes.

  13. 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.

  14. Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury.

    PubMed

    Gao, Shuang; Zhang, Zhong-Ming; Shen, Zhao-Liang; Gao, Kai; Chang, Liang; Guo, Yue; Li, Zhuo; Wang, Wei; Wang, Ai-Mei

    2016-06-01

    Atorvastatin, a lipid-lowering medication, provides neuroprotective effects, although the precise mechanisms of action remain unclear. Our previous studies confirmed activated autophagy following spinal cord injury, which was conducive to recovery of neurological functions. We hypothesized that atorvastatin could also activate autophagy after spinal cord injury, and subsequently improve recovery of neurological functions. A rat model of spinal cord injury was established based on the Allen method. Atorvastatin (5 mg/kg) was intraperitoneally injected at 1 and 2 days after spinal cord injury. At 7 days post-injury, western blot assay, reverse transcription-polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining results showed increased Beclin-1 and light chain 3B gene and protein expressions in the spinal cord injury + atorvastatin group. Additionally, caspase-9 and caspase-3 expression was decreased, and the number of TUNEL-positive cells was reduced. Compared with the spinal cord injury + saline group, Basso, Beattie, and Bresnahan locomotor rating scale scores significantly increased in the spinal cord injury + atorvastatin group at 14-42 days post-injury. These findings suggest that atorvastatin activated autophagy after spinal cord injury, inhibited apoptosis, and promoted recovery of neurological function. PMID:27482228

  15. 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

  16. Functional Magnetic Resonance Imaging for Imaging Neural Activity in the Human Brain: The Annual Progress

    PubMed Central

    Chen, Shengyong; Li, Xiaoli

    2012-01-01

    Functional magnetic resonance imaging (fMRI) is recently developed and applied to measure the hemodynamic response related to neural activity. The fMRI can not only noninvasively record brain signals without risks of ionising radiation inherent in other scanning methods, such as CT or PET scans, but also record signal from all regions of the brain, unlike EEG/MEG which are biased towards the cortical surface. This paper introduces the fundamental principles and summarizes the research progress of the last year for imaging neural activity in the human brain. Aims of functional analysis of neural activity from fMRI include biological findings, functional connectivity, vision and hearing research, emotional research, neurosurgical planning, pain management, and many others. Besides formulations and basic processing methods, models and strategies of processing technology are introduced, including general linear model, nonlinear model, generative model, spatial pattern analysis, statistical analysis, correlation analysis, and multimodal combination. This paper provides readers the most recent representative contributions in the area. PMID:22319550

  17. 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.

  18. Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury

    PubMed Central

    Gao, Shuang; Zhang, Zhong-ming; Shen, Zhao-liang; Gao, Kai; Chang, Liang; Guo, Yue; Li, Zhuo; Wang, Wei; Wang, Ai-mei

    2016-01-01

    Atorvastatin, a lipid-lowering medication, provides neuroprotective effects, although the precise mechanisms of action remain unclear. Our previous studies confirmed activated autophagy following spinal cord injury, which was conducive to recovery of neurological functions. We hypothesized that atorvastatin could also activate autophagy after spinal cord injury, and subsequently improve recovery of neurological functions. A rat model of spinal cord injury was established based on the Allen method. Atorvastatin (5 mg/kg) was intraperitoneally injected at 1 and 2 days after spinal cord injury. At 7 days post-injury, western blot assay, reverse transcription-polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining results showed increased Beclin-1 and light chain 3B gene and protein expressions in the spinal cord injury + atorvastatin group. Additionally, caspase-9 and caspase-3 expression was decreased, and the number of TUNEL-positive cells was reduced. Compared with the spinal cord injury + saline group, Basso, Beattie, and Bresnahan locomotor rating scale scores significantly increased in the spinal cord injury + atorvastatin group at 14–42 days post-injury. These findings suggest that atorvastatin activated autophagy after spinal cord injury, inhibited apoptosis, and promoted recovery of neurological function. PMID:27482228

  19. Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury.

    PubMed

    Gao, Shuang; Zhang, Zhong-Ming; Shen, Zhao-Liang; Gao, Kai; Chang, Liang; Guo, Yue; Li, Zhuo; Wang, Wei; Wang, Ai-Mei

    2016-06-01

    Atorvastatin, a lipid-lowering medication, provides neuroprotective effects, although the precise mechanisms of action remain unclear. Our previous studies confirmed activated autophagy following spinal cord injury, which was conducive to recovery of neurological functions. We hypothesized that atorvastatin could also activate autophagy after spinal cord injury, and subsequently improve recovery of neurological functions. A rat model of spinal cord injury was established based on the Allen method. Atorvastatin (5 mg/kg) was intraperitoneally injected at 1 and 2 days after spinal cord injury. At 7 days post-injury, western blot assay, reverse transcription-polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining results showed increased Beclin-1 and light chain 3B gene and protein expressions in the spinal cord injury + atorvastatin group. Additionally, caspase-9 and caspase-3 expression was decreased, and the number of TUNEL-positive cells was reduced. Compared with the spinal cord injury + saline group, Basso, Beattie, and Bresnahan locomotor rating scale scores significantly increased in the spinal cord injury + atorvastatin group at 14-42 days post-injury. These findings suggest that atorvastatin activated autophagy after spinal cord injury, inhibited apoptosis, and promoted recovery of neurological function.

  20. 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.

  1. 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. PMID:26488557

  2. Functional magnetic resonance imaging for imaging neural activity in the human brain: the annual progress.

    PubMed

    Chen, Shengyong; Li, Xiaoli

    2012-01-01

    Functional magnetic resonance imaging (fMRI) is recently developed and applied to measure the hemodynamic response related to neural activity. The fMRI can not only noninvasively record brain signals without risks of ionising radiation inherent in other scanning methods, such as CT or PET scans, but also record signal from all regions of the brain, unlike EEG/MEG which are biased towards the cortical surface. This paper introduces the fundamental principles and summarizes the research progress of the last year for imaging neural activity in the human brain. Aims of functional analysis of neural activity from fMRI include biological findings, functional connectivity, vision and hearing research, emotional research, neurosurgical planning, pain management, and many others. Besides formulations and basic processing methods, models and strategies of processing technology are introduced, including general linear model, nonlinear model, generative model, spatial pattern analysis, statistical analysis, correlation analysis, and multimodal combination. This paper provides readers the most recent representative contributions in the area.

  3. 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.

  4. The Ras/Rap GTPase activating protein RASA3: from gene structure to in vivo functions.

    PubMed

    Schurmans, Stéphane; Polizzi, Séléna; Scoumanne, Ariane; Sayyed, Sufyan; Molina-Ortiz, Patricia

    2015-01-01

    RASA3 (or GTPase Activating Protein III, R-Ras GTPase-activating protein, GAP1(IP4BP)) is a GTPase activating protein of the GAP1 subfamily which targets Ras and Rap1. RASA3 was originally purified from pig platelet membranes through its intrinsic ability to bind inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with high affinity, hence its first name GAP1(IP4BP) (for GAP1 subfamily member which binds I(1,3,4,5)P4). RASA3 was thus the first I(1,3,4,5)P4 receptor identified and cloned. The in vitro and in vivo functions of RASA3 remained somewhat elusive for a long time. However, recently, using genetically-modified mice and cells derived from these mice, the function of RASA3 during megakaryopoiesis, megakaryocyte adhesion and migration as well as integrin signaling has been reported. The goal of this review is thus to summarize and comment recent and less recent data in the literature on RASA3, in particular on the in vivo function of this specific GAP1 subfamily member.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. Improvement of Processing Speed in Executive Function Immediately following an Increase in Cardiovascular Activity

    PubMed Central

    Tam, Nicoladie D.

    2013-01-01

    This study aims to identify the acute effects of physical exercise on specific cognitive functions immediately following an increase in cardiovascular activity. Stair-climbing exercise is used to increase the cardiovascular output of human subjects. The color-naming Stroop Test was used to identify the cognitive improvements in executive function with respect to processing speed and error rate. The study compared the Stroop results before and immediately after exercise and before and after nonexercise, as a control. The results show that there is a significant increase in processing speed and a reduction in errors immediately after less than 30 min of aerobic exercise. The improvements are greater for the incongruent than for the congruent color tests. This suggests that physical exercise induces a better performance in a task that requires resolving conflict (or interference) than a task that does not. There is no significant improvement for the nonexercise control trials. This demonstrates that an increase in cardiovascular activity has significant acute effects on improving the executive function that requires conflict resolution (for the incongruent color tests) immediately following aerobic exercise more than similar executive functions that do not require conflict resolution or involve the attention-inhibition process (for the congruent color tests). PMID:24187613

  10. 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

  11. High-throughput mutagenesis reveals functional determinants for DNA targeting by activation-induced deaminase

    PubMed Central

    Gajula, Kiran S.; Huwe, Peter J.; Mo, Charlie Y.; Crawford, Daniel J.; Stivers, James T.; Radhakrishnan, Ravi; Kohli, Rahul M.

    2014-01-01

    Antibody maturation is a critical immune process governed by the enzyme activation-induced deaminase (AID), a member of the AID/APOBEC DNA deaminase family. AID/APOBEC deaminases preferentially target cytosine within distinct preferred sequence motifs in DNA, with specificity largely conferred by a small 9–11 residue protein loop that differs among family members. Here, we aimed to determine the key functional characteristics of this protein loop in AID and to thereby inform our understanding of the mode of DNA engagement. To this end, we developed a methodology (Sat-Sel-Seq) that couples saturation mutagenesis at each position across the targeting loop, with iterative functional selection and next-generation sequencing. This high-throughput mutational analysis revealed dominant characteristics for residues within the loop and additionally yielded enzymatic variants that enhance deaminase activity. To rationalize these functional requirements, we performed molecular dynamics simulations that suggest that AID and its hyperactive variants can engage DNA in multiple specific modes. These findings align with AID's competing requirements for specificity and flexibility to efficiently drive antibody maturation. Beyond insights into the AID-DNA interface, our Sat-Sel-Seq approach also serves to further expand the repertoire of techniques for deep positional scanning and may find general utility for high-throughput analysis of protein function. PMID:25064858

  12. 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

  13. 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

  14. Antioxidant activities and functional properties of protein and peptide fractions isolated from salted herring brine.

    PubMed

    Taheri, Ali; Sabeena Farvin, K H; Jacobsen, Charlotte; Baron, Caroline P

    2014-01-01

    In the present study proteins isolated from herring brine, which is a by-product of marinated herring production were evaluated for their functional properties and antioxidant activity. Herring brine was collected from the local herring industry and proteins were precipitated by adjusting the pH to 4.5 and the obtained supernatant was further fractionated by using ultrafiltration membranes with molecular weight cut offs of 50, 10 and 1kDa. The obtained >50kDa, 50-10kDa, 10-1kDa fractions and pH precipitated fraction were studied for their functional properties and antioxidant activity. Functional properties revealed that >50kDa polypeptides showed good emulsion activity index when compared to the other fractions. However all fractions had low emulsion stability index. The pH precipitated fraction showed the highest foaming capacity and stability at pH 10. The 50-10kDa and 10-1kDa peptide fractions showed good radical scavenging activity and reducing power at a concentration of 0.5mg protein/ml. All the fractions demonstrated low iron chelating activity and did not inhibit oxidation in a soybean phosphatidylcholine liposome model system. However all the fractions were to some extent able to delay iron catalyzed lipid oxidation in 5% fish oil in water emulsions and the 10-50kDa fraction was the best. These results show the potential of proteins and peptide fractions recovered from waste water from the herring industry as source of natural antioxidants for use in food products.

  15. RNA silencing of genes involved in Alzheimer's disease enhances mitochondrial function and synaptic activity.

    PubMed

    Manczak, Maria; Reddy, P Hemachandra

    2013-12-01

    An age-dependent increase in mRNA levels of the amyloid precursor protein (APP), the microtubule-associated protein Tau, and voltage-dependent anion channel 1 (VDAC1) genes are reported to be toxic to neurons affected by Alzheimer's disease (AD). However, the underlying toxic nature of these genes is not completely understood. The purpose of our study was to determine the effects of RNA silencing of APP, Tau, and VDAC1 genes in AD pathogenesis. Using human neuroblastoma (SHSY5Y) cells, we first silenced RNA for APP, Tau, and VDAC1 genes, and then performed real-time RT-PCR analysis to measure mRNA levels of 34 genes that are involved in AD pathogenesis. Using biochemical assays, we also assessed mitochondrial function by measuring levels of H2O2 production, lipid peroxidation, cytochrome c oxidase activity, ATP production, and GTPase enzymatic activity. We found that increased mRNA expression of synaptic function and mitochondrial fission genes, and reduced levels of mitochondrial fusion genes in RNA silenced the SHSY5Y cells for APP, Tau and VDAC1 genes relative to the control SHSY5Y cells. In addition, RNA-silenced APP, Tau, and VDAC1 genes in SHSY5Y cells showed reduced levels of H2O2 production, lipid peroxidation, fission-linked GTPase activity, and increased cytochrome oxidase activity and ATP production. These findings suggest that a reduction of human APP, Tau, and VDAC1 may enhance synaptic activity, may improve mitochondrial maintenance and function, and may protect against toxicities of AD-related genes. Thus, these findings also suggest that the reduction of APP, Tau, and VDAC1 mRNA expressions may have therapeutic value for patients with AD.

  16. Chronic activation of the kinase IKKβ impairs T cell function and survival

    PubMed Central

    Krishna, Sruti; Xie, Danli; Gorentla, Balachandra; Shin, Jinwook; Gao, Jimin; Zhong, Xiao-Ping

    2012-01-01

    Activation of the transcription factor NF-κB is critical for cytokine production and T cell survival after T cell receptor (TCR) engagement. The effects of persistent NF-κB activity on T cell function and survival are poorly understood. In this study, using a murine model that expresses a constitutively active form of inhibitor of κB kinase β(caIKKβ) in a T-cell specific manner, we demonstrate that chronic IKKβ signaling promotes T cell apoptosis, attenuates responsiveness to TCR-mediated stimulation in vitro, and impairs T cell responses to bacterial infection in vivo. CaIKKβ T cells showed increased FasL expression and caspase-8 activation, and blocking Fas/FasL interactions enhanced cell survival. T cell unresponsiveness was associated with defects in TCR proximal signaling, and elevated levels of Blimp1, a transcriptional repressor that promotes T cell exhaustion. CaIKKβ T cells also showed a defect in IL-2 production, and addition of exogenous IL-2 enhanced their survival and proliferation. Conditional deletion of Blimp1 partially rescued sensitivity of caIKKβ T cells to TCR triggering. Furthermore, adoptively transferred caIKKβ T cells showed diminished expansion and increased contraction in response to infection with Listeria monocytogenes expressing a cognate antigen. Despite their functional defects, caIKKβ T cells readily produced pro-inflammatory cytokines and mice developed autoimmunity. In contrast to NF-κB's critical role in T cell activation and survival, our study demonstrates that persistent IKK-NF-κB signaling is sufficient to impair both T cell function and survival. PMID:22753932

  17. 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.

  18. Effect of functionalization of carbon nanotubes with psychosine on complement activation and protein adsorption.

    PubMed

    Rybak-Smith, Malgorzata J; Tripisciano, Carla; Borowiak-Palen, Ewa; Lamprecht, Constanze; Sim, Robert B

    2011-12-01

    Carbon nanotubes possess interesting physicochemical properties which make them potentially usable in medicine. Single-walled carbon nanotubes and multi-walled carbon nanotubes, for example, may carry and deliver anticancer drugs, such as cisplatin. Magnetic nanoparticles, like iron filled MWCNT, can be used in hyperthermia therapy. However, their hydrophobic character is a major difficulty, as preparation of stable dispersions of carbon nanotubes in biological buffers is an essential step towards biomedical applications. Recently, a novel treatment using the glycolipid, Galactosyl-beta1-sphingosine (psychosine), was employed to make stable suspensions of psychosine-functionalized carbon nanotubes in biological buffers. In this paper, the interactions of psychosine-functionalized carbon nanotubes with a part of the human immune system, complement, is presented. To investigate if human serum complement proteins can interact with psychosine-functionalized carbon nanotubes, complement consumption (depletion) assays were conducted. Moreover, direct protein binding studies, to analyze the interaction of plasma proteins with the psychosine-functionalized carbon nanotubes, using affinity chromatography and sodium dodecyl sulphate polyacrylamide gel electrophoresis techniques, were applied. The psychosine-functionalized carbon nanotubes activate human complement via the classical pathway. Interestingly, as the hydrophilic part of the glycolipid may bind to ficolins, the lectin pathway could also be involved. Binding of human plasma proteins is very selective as only very few proteins adsorb to the psychosine-functionalized carbon nanotube surface, when placed in contact with human plasma. Bovine serum albumin-coated carbon nanotubes were used as a standard to find the differences in complement activation and protein adsorption patterns, caused by various non-covalent coatings of carbon nanotubes.

  19. Towards an automated selection of spontaneous co-activity maps in functional magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Sourty, Marion; Thoraval, Laurent; Roquet, Daniel; Armspach, Jean-Paul; Foucher, Jack

    2015-03-01

    Functional magnetic resonance imaging allows to assess large scale functional integration of the brain. One of the leading techniques to extract functionally relevant networks is spatial independent component analysis (ICA). Spatial ICA separates independent spatial sources, many of whom are noise or imaging artifacts, whereas some do correspond to functionally relevant Spontaneous co-Activity Maps (SAMs). For research purposes, ICA is generally performed on group data. This strategy is well adapted to uncover commonly shared networks, e.g. resting-state networks, but fails to capture idiosyncratic functional networks which may be related to pathological activity, e.g. epilepsy, hallucinations. To capture these subject specific networks, ICA has to be applied to single subjects using a large number of components, from which a tenth are SAMs. Up to now, SAMs have to be selected manually by an expert based on predefined criteria. We aim to semi-automate the selection process in order to save time. To this end, some approaches have been proposed but none with the near 100 % sensitivity required for clinical purposes. In this paper, we propose a computerized version of the SAM's criteria used by experts, based on frequential and spatial characteristics of functional networks. Here we present a pre-selection method and its results at different resolutions, with different scanners or imaging sequences. While preserving a near 100 % sensitivity, it allows an average of 70 % reduction of components to be classified which save 55% of experts' time. In comparison, group ICA fails to detect about 25% of the SAMs.

  20. Dualistic nature of adhesive protein function: fibronectin and its biologically active peptide fragments can autoinhibit fibronectin function

    PubMed Central

    1984-01-01

    Fibronectin and certain polypeptide regions of this adhesive glycoprotein mediate cell attachment and spreading on various substrates. We explored the theoretical prediction that this adhesive protein could become a competitive inhibitor of fibronectin-mediated processes if present in solution at appropriately high concentrations. Fibronectin function was inhibited by purified plasma fibronectin at 5- 10 mg/ml, by a 75,000-dalton cell-interaction fragment of the protein at 0.5-1 mg/ml, and even by two synthetic peptides containing a conserved, hydrophilic amino acid sequence at 0.1-0.5 mg/ml. Inhibition of fibronectin-dependent cell spreading was dose dependent, noncytotoxic, and reversible. It was competitive in nature, since increased quantities of substrate-adsorbed fibronectin or longer incubation periods decreased the inhibition. A peptide inhibitory for fibronectin-mediated cell spreading also inhibited fibronectin-mediated attachment of cells to type I collagen, but it did not affect concanavalin A-mediated spreading. These results demonstrate the potential of a cell adhesion molecule and its biologically active peptide fragments to act as competitive inhibitors, and they suggest that fibronectin may act by binding to a saturable cell surface receptor. PMID:6736130

  1. Results of a workshop concerning impacts of various activities on the functions of bottomland hardwoods

    USGS Publications Warehouse

    Roelle, James E.; Auble, Gregor T.; Hamilton, David B.; Horak, Gerald C.; Johnson, Richard L.; Segelquist, Charles A.

    1987-01-01

    Under Section 404 of the Clean Water Act, the U.S. Environmental Protection Agency (EPA) has regulatory responsibilities related to the discharge of dredged or fill material into the Nation’s waters. In addition to its advisory role in the U.S. Army Corps of Engineers' permit program, EPA has a number of specific authorities, including formulation of the Section 404(b)(1) guidelines, use of Section 404(c) to prohibit disposal at particular sites, and enforcement actions for unauthorized discharges. A number of recent court cases focus on the geographic scope of Section 404 jurisdiction in potential bottomland hardwood (BLH) wetlands and the nature of landclearing activities in these areas that require a permit under Section 404. Accordingly, EPA needs to establish the scientific basis for implementing its responsibilities under Section 404 in bottomland hardwoods. EPA is approaching this task through a series of workshops designed to provide current scientific information on bottomland hardwoods and to organize that information in a manner pertinent to key policy questions. The first two workshops in the series were originally conceived as technically oriented meetings that would provide the information necessary to develop policy options at the third workshop. More specifically, the first workshop was designed to examine a zonation concept as a means of characterizing different BLH communities and describing variations in their functions along a soil moisture gradient. The second workshop was perceived as an attempt to evaluate the impacts of various activities on those functions. However, one conclusion of the first workshop, which was held in December 1984 in St. Francisville, Louisiana, was that the zonation approach does not describe the variability in the functions performed by BLH ecosystems sufficiently well to allow its use as the sole basis for developing a regulatory framework. That is, factors other than zone were considered critical for an effective

  2. Induction of mixed-function oxidase activity in mouse lymphoid tissues by polycyclic aromatic hydrocarbons

    SciTech Connect

    Griffin, G.D.; Egan, B.Z.; Lee, N.E.; Burtis, C.A.

    1986-01-01

    Polycyclic aromatic hydrocarbon (PAH) exposure can cause mixed-function oxidase (MFO) enzyme induction in certain tissues of various organisms. Measurements of such induction might serve as a useful bioindicator of human exposure to PAHs, provided readily obtainable human tissues can be utilized for such measurements. The authors have investigated the MFO activity in various lymphoid tissues of the C3H mouse as a model system and have studied the effect of systemic PAH treatment on such enzyme activity. An MFO enzyme assay was used to measure the activity of 7-ethoxyresorufin deethylase, an enzyme activity that may be specific for the cytochrome P-448 subset of MFO enzymes (those enzymes that are induced in cells or tissues following PAH administration). Intraperitoneal injection of mice with 180 mg/kg (4.6 mg) benzo(a)pyrene (BaP) or 160 mg/kg (4.0 mg) 3-methylcholanthrene (MC) produced a significant induction in MFO activity in mouse spleen S9 fractions 48 h after the injection. Induction ratios (induced activity/control activity) between 4 and 5 were seen with BaP; MC produced induction ratios of 2.5-3.0. Enzyme activity was not induced in the spleen within 16 h following BaP or MC administration. Other experiments indicated that MFO activity could be induced in thymus cells 48 h after either BaP or MC treatment. Treatment with BaP or MC did produce significant enzyme induction in the liver and lung tissues from the animals both 16 and 48 h after chemical treatment.

  3. Influence of skin penetration enhancers on skin barrier function and skin protease activity.

    PubMed

    Mohammed, Diar; Hirata, Kazumasa; Hadgraft, Jonathan; Lane, Majella E

    2014-01-23

    In order to overcome the skin's excellent barrier function formulation scientists often employ skin penetration enhancers (SPEs) in topical and transdermal formulations. The effects of these compounds on skin health is still not well understood at the molecular level. The aim of the present work was to probe the effects of some common SPEs on desquamatory protease activity in healthy skin. The SPEs studied were isopropyl myristate (IPM), propylene glycol, (PG), propylene glycol laurate (PGL) and Transcutol™ (TC). Occluded infinite doses of each SPE were applied to human volunteers for 24 h. Transepidermal water loss (TEWL) measurements were taken before and after application of SPEs. Tape strips were collected from the treated sites to determine protein content and the activity of two desquamatory proteases kallikrein 5 (KLK5) and kallikrein 7 (KLK7). TEWL values were also measured after tape stripping. PG was found to elevate both TEWL values and KLK7 activity to a significant extent (p<0.05). No significant effects were observed for the other SPEs. The ability of PG to alter the skin barrier at the macroscopic level and the influence of the molecule on protease activity reported here may have implications for its use in topical formulations used for the management of impaired skin barrier function such as atopic eczema or psoriasis. PMID:24063883

  4. Arginase induction and activation during ischemia and reperfusion and functional consequences for the heart

    PubMed Central

    Schlüter, Klaus-Dieter; Schulz, Rainer; Schreckenberg, Rolf

    2015-01-01

    Induction and activation of arginase is among the fastest responses of the heart to ischemic events. Induction of arginase expression and enzyme activation under ischemic conditions shifts arginine consumption from nitric oxide formation (NO) to the formation of ornithine and urea. In the heart such a switch in substrate utilization reduces the impact of the NO/cGMP-pathway on cardiac function that requires intact electromechanical coupling but at the same time it induces ornithine-dependent pathways such as the polyamine metabolism. Both effects significantly reduce the recovery of heart function during reperfusion and thereby limits the success of reperfusion strategies. In this context, changes in arginine consumption trigger cardiac remodeling in an unfavorable way and increases the risk of arrhythmia, specifically in the initial post-ischemic period in which arginase activity is dominating. However, during the entire ischemic period arginase activation might be a meaningful adaptation that is specifically relevant for reperfusion following prolonged ischemic periods. Therefore, a precise understanding about the underlying mechanism that leads to arginase induction as well as of it's mechanistic impact on post-ischemic hearts is required for optimizing reperfusion strategies. In this review we will summarize our current understanding of these processes and give an outlook about possible treatment options for the future. PMID:25814956

  5. Risk of decline in functional activities in dementia with Lewy bodies and Alzheimer disease.

    PubMed

    Gill, Dawn P; Koepsell, Thomas D; Hubbard, Rebecca A; Kukull, Walter A

    2011-01-01

    We examined the risk of 1-year decline in 4 everyday activities in patients with dementia with Lewy bodies (DLB), relative to patients with Alzheimer disease (AD). Data were from the National Alzheimer's Coordinating Center, gathered from 32 Alzheimer's Disease Centers. Participants (n=1880) were: aged 60+ years, demented with a primary clinical diagnosis of probable AD or DLB, and had a global Clinical Dementia Rating of 0.5 to 2. The activities were measured with the Functional Activities Questionnaire. In modified Poisson regression models adjusted for demographics, baseline activity, years from symptom onset, cognitive impairment, and comorbidities; DLB participants aged 67 to 81 years had 1.5 to 2 times increased risk of decline in performing basic kitchen tasks, engaging in games/hobbies, and paying attention/understanding, relative to AD participants of the same age (P<0.05). There was no significant difference between AD and DLB participants beyond this age range. For decline in ability to go shopping alone, there was also no significant difference between AD and DLB participants. In summary, the functional course of DLB, relative to AD, may depend on the age of the patient. These findings may provide anticipatory guidance to families and healthcare providers, which may be useful in the planning of care strategies.

  6. Circadian Activators Are Expressed Days before They Initiate Clock Function in Late Pacemaker Neurons from Drosophila.

    PubMed

    Liu, Tianxin; Mahesh, Guruswamy; Houl, Jerry H; Hardin, Paul E

    2015-06-01

    Circadian pacemaker neurons in the Drosophila brain control daily rhythms in locomotor activity. These pacemaker neurons can be subdivided into early or late groups depending on whether rhythms in period (per) and timeless (tim) expression are initiated at the first instar (L1) larval stage or during metamorphosis, respectively. Because CLOCK-CYCLE (CLK-CYC) heterodimers initiate circadian oscillator function by activating per and tim transcription, a Clk-GFP transgene was used to mark when late pacemaker neurons begin to develop. We were surprised to see that CLK-GFP was already expressed in four of five clusters of late pacemaker neurons during the third instar (L3) larval stage. CLK-GFP is only detected in postmitotic neurons from L3 larvae, suggesting that these four late pacemaker neuron clusters are formed before the L3 larval stage. A GFP-cyc transgene was used to show that CYC, like CLK, is also expressed exclusively in pacemaker neurons from L3 larval brains, demonstrating that CLK-CYC is not sufficient to activate per and tim in late pacemaker neurons at the L3 larval stage. These results suggest that most late pacemaker neurons develop days before novel factors activate circadian oscillator function during metamorphosis.

  7. Research on acupuncture points and cortical functional activation position in cats by infrared imaging detection

    NASA Astrophysics Data System (ADS)

    Chen, Shuwang; Sha, Zhanyou; Wang, Shuhai; Wen, Huanming

    2007-12-01

    The research of the brain cognition is mainly to find out the activation position in brain according to the stimulation at present in the world. The research regards the animals as the experimental objects and explores the stimulation response on the cerebral cortex of acupuncture. It provides a new method, which can detect the activation position on the creatural cerebral cortex directly by middle-far infrared imaging. According to the theory of local temperature situation, the difference of cortical temperature maybe associate with the excitement of cortical nerve cells, the metabolism of local tissue and the local hemal circulation. Direct naked detection of temperature variety on cerebral cortex is applied by middle and far infrared imaging technology. So the activation position is ascertained. The effect of stimulation response is superior to other indirect methods. After removing the skulls on the head, full of cerebral cortex of a cat are exposed. By observing the infrared images and measuring the temperatures of the visual cerebral cortex during the process of acupuncturing, the points are used to judge the activation position. The variety in the cortical functional sections is corresponding to the result of the acupuncture points in terms of infrared images and temperatures. According to experimental results, we know that the variety of a cortical functional section is corresponding to a special acupuncture point exactly.

  8. Two Dictyostelium tyrosine kinase–like kinases function in parallel, stress-induced STAT activation pathways

    PubMed Central

    Araki, Tsuyoshi; Vu, Linh Hai; Sasaki, Norimitsu; Kawata, Takefumi; Eichinger, Ludwig; Williams, Jeffrey G.

    2014-01-01

    When Dictyostelium cells are hyperosmotically stressed, STATc is activated by tyrosine phosphorylation. Unusually, activation is regulated by serine phosphorylation and consequent inhibition of a tyrosine phosphatase: PTP3. The identity of the cognate tyrosine kinase is unknown, and we show that two tyrosine kinase–like (TKL) enzymes, Pyk2 and Pyk3, share this function; thus, for stress-induced STATc activation, single null mutants are only marginally impaired, but the double mutant is nonactivatable. When cells are stressed, Pyk2 and Pyk3 undergo increased autocatalytic tyrosine phosphorylation. The site(s) that are generated bind the SH2 domain of STATc, and then STATc becomes the target of further kinase action. The signaling pathways that activate Pyk2 and Pyk3 are only partially overlapping, and there may be a structural basis for this difference because Pyk3 contains both a TKL domain and a pseudokinase domain. The latter functions, like the JH2 domain of metazoan JAKs, as a negative regulator of the kinase domain. The fact that two differently regulated kinases catalyze the same phosphorylation event may facilitate specific targeting because under stress, Pyk3 and Pyk2 accumulate in different parts of the cell; Pyk3 moves from the cytosol to the cortex, whereas Pyk2 accumulates in cytosolic granules that colocalize with PTP3. PMID:25143406

  9. Synthesis, algal inhibition activities and QSAR studies of novel gramine compounds containing ester functional groups

    NASA Astrophysics Data System (ADS)

    Li, Xia; Yu, Liangmin; Jiang, Xiaohui; Xia, Shuwei; Zhao, Haizhou

    2009-05-01

    2,5,6-Tribromo-1-methylgramine (TBG), isolated from bryozoan Zoobotryon pellucidum was shown to be very efficient in preventing recruitment of larval settlement. In order to improve the compatibility of TBG and its analogues with other ingredients in antifouling paints, structural modification of TBG was focused mainly on halogen substitution and N-substitution. Two halogen-substitute gramines and their derivatives which contain ester functional groups at N-position of gramines were synthesized. Algal inhibition activities of the synthesized compounds against algae Nitzschia closterium were evaluated and the Median Effective Concentration (EC50) range was 1.06-6.74 μg ml-1. Compounds that had a long chain ester group exhibited extremely high antifouling activity. Quantitive Structure Activity Relationship (QSAR) studies with multiple linear regression analysis were applied to find correlation between different calculated molecular descriptors and biological activity of the synthesized compounds. The results show that the toxicity (log (1/EC50)) is correlated well with the partition coefficient log P. Thus, these products have potential function as antifouling agents.

  10. Functional analysis of TPM domain containing Rv2345 of Mycobacterium tuberculosis identifies its phosphatase activity.

    PubMed

    Sinha, Avni; Eniyan, Kandasamy; Sinha, Swati; Lynn, Andrew Michael; Bajpai, Urmi

    2015-07-01

    Mycobacterium tuberculosis (Mtb) is the causal agent of tuberculosis, the second largest infectious disease. With the rise of multi-drug resistant strains of M. tuberculosis, serious challenge lies ahead of us in treating the disease. The availability of complete genome sequence of Mtb has improved the scope for identifying new proteins that would not only further our understanding of biology of the organism but could also serve to discover new drug targets. In this study, Rv2345, a hypothetical membrane protein of M. tuberculosis H37Rv, which is reported to be a putative ortholog of ZipA cell division protein has been assigned function through functional annotation using bioinformatics tools followed by experimental validation. Sequence analysis showed Rv2345 to have a TPM domain at its N-terminal region and predicted it to have phosphatase activity. The TPM domain containing region of Rv2345 was cloned and expressed using pET28a vector in Escherichia coli and purified by Nickel affinity chromatography. The purified TPM domain was tested in vitro and our results confirmed it to have phosphatase activity. The enzyme activity was first checked and optimized with pNPP as substrate, followed by using ATP, which was also found to be used as substrate by the purified protein. Hence sequence analysis followed by in vitro studies characterizes TPM domain of Rv2345 to contain phosphatase activity.

  11. A Combined sEMG and Accelerometer System for Monitoring Functional Activity in Stroke

    PubMed Central

    Roy, Serge H.; Cheng, M. Samuel; Chang, Shey-Sheen; Moore, John; De Luca, Gianluca; Nawab, S. Hamid; De Luca, Carlo J.

    2010-01-01

    Remote monitoring of physical activity using body-worn sensors provides an alternative to assessment of functional independence by subjective, paper-based questionnaires. This study investigated the classification accuracy of a combined surface electromyographic (sEMG) and accelerometer (ACC) sensor system for monitoring activities of daily living in patients with stroke. sEMG and ACC data (eight channels each) were recorded from 10 hemiparetic patients while they carried out a sequence of 11 activities of daily living (identification tasks), and 10 activities used to evaluate misclassification errors (nonidentification tasks). The sEMG and ACC sensor data were analyzed using a multilayered neural network and an adaptive neuro-fuzzy inference system to identify the minimal sensor configuration needed to accurately classify the identification tasks, with a minimal number of misclassifications from the nonidentification tasks. The results demonstrated that the highest sensitivity and specificity for the identification tasks was achieved using a subset of four ACC sensors and adjacent sEMG sensors located on both upper arms, one forearm, and one thigh, respectively. This configuration resulted in a mean sensitivity of 95.0%, and a mean specificity of 99.7% for the identification tasks, and a mean misclassification error of <10% for the nonidentification tasks. The findings support the feasibility of a hybrid sEMG and ACC wearable sensor system for automatic recognition of motor tasks used to assess functional independence in patients with stroke. PMID:20051332

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