Sample records for cooperatively regulate abre-dependent

  1. AREB1, AREB2, and ABF3 are master transcription factors that cooperatively regulate ABRE-dependent ABA signaling involved in drought stress tolerance and require ABA for full activation.

    PubMed

    Yoshida, Takuya; Fujita, Yasunari; Sayama, Hiroko; Kidokoro, Satoshi; Maruyama, Kyonoshin; Mizoi, Junya; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2010-02-01

    A myriad of drought stress-inducible genes have been reported, and many of these are activated by abscisic acid (ABA). In the promoter regions of such ABA-regulated genes, conserved cis-elements, designated ABA-responsive elements (ABREs), control gene expression via bZIP-type AREB/ABF transcription factors. Although all three members of the AREB/ABF subfamily, AREB1, AREB2, and ABF3, are upregulated by ABA and water stress, it remains unclear whether these are functional homologs. Here, we report that all three AREB/ABF transcription factors require ABA for full activation, can form hetero- or homodimers to function in nuclei, and can interact with SRK2D/SnRK2.2, an SnRK2 protein kinase that was identified as a regulator of AREB1. Along with the tissue-specific expression patterns of these genes and the subcellular localization of their encoded proteins, these findings clearly indicate that AREB1, AREB2, and ABF3 have largely overlapping functions. To elucidate the role of these AREB/ABF transcription factors, we generated an areb1 areb2 abf3 triple mutant. Large-scale transcriptome analysis, which showed that stress-responsive gene expression is remarkably impaired in the triple mutant, revealed novel AREB/ABF downstream genes in response to water stress, including many LEA class and group-Ab PP2C genes and transcription factors. The areb1 areb2 abf3 triple mutant is more resistant to ABA than are the other single and double mutants with respect to primary root growth, and it displays reduced drought tolerance. Thus, these results indicate that AREB1, AREB2, and ABF3 are master transcription factors that cooperatively regulate ABRE-dependent gene expression for ABA signaling under conditions of water stress.

  2. An ABRE promoter sequence is involved in osmotic stress-responsive expression of the DREB2A gene, which encodes a transcription factor regulating drought-inducible genes in Arabidopsis.

    PubMed

    Kim, June-Sik; Mizoi, Junya; Yoshida, Takuya; Fujita, Yasunari; Nakajima, Jun; Ohori, Teppei; Todaka, Daisuke; Nakashima, Kazuo; Hirayama, Takashi; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2011-12-01

    In plants, osmotic stress-responsive transcriptional regulation depends mainly on two major classes of cis-acting elements found in the promoter regions of stress-inducible genes: ABA-responsive elements (ABREs) and dehydration-responsive elements (DREs). ABRE has been shown to perceive ABA-mediated osmotic stress signals, whereas DRE is known to be involved in an ABA-independent pathway. Previously, we reported that the transcription factor DRE-BINDING PROTEIN 2A (DREB2A) regulates DRE-mediated transcription of target genes under osmotic stress conditions in Arabidopsis (Arabidopsis thaliana). However, the transcriptional regulation of DREB2A itself remains largely uncharacterized. To elucidate the transcriptional mechanism associated with the DREB2A gene under osmotic stress conditions, we generated a series of truncated and base-substituted variants of the DREB2A promoter and evaluated their transcriptional activities individually. We found that both ABRE and coupling element 3 (CE3)-like sequences located approximately -100 bp from the transcriptional initiation site are necessary for the dehydration-responsive expression of DREB2A. Coupling our transient expression analyses with yeast one-hybrid and chromatin immunoprecipitation (ChIP) assays indicated that the ABRE-BINDING PROTEIN 1 (AREB1), AREB2 and ABRE-BINDING FACTOR 3 (ABF3) bZIP transcription factors can bind to and activate the DREB2A promoter in an ABRE-dependent manner. Exogenous ABA application induced only a modest accumulation of the DREB2A transcript when compared with the osmotic stress treatment. However, the osmotic stress-induced DREB2A expression was found to be markedly impaired in several ABA-deficient and ABA-insensitive mutants. These results suggest that in addition to an ABA-independent pathway, the ABA-dependent pathway plays a positive role in the osmotic stress-responsive expression of DREB2A.

  3. Transactivation of the Brassica napus napin promoter by ABI3 requires interaction of the conserved B2 and B3 domains of ABI3 with different cis-elements: B2 mediates activation through an ABRE, whereas B3 interacts with an RY/G-box.

    PubMed

    Ezcurra, I; Wycliffe, P; Nehlin, L; Ellerström, M; Rask, L

    2000-10-01

    The transcriptional activator ABI3 is a key regulator of gene expression during embryo maturation in crucifers. In monocots, the related VP1 protein regulates the Em promoter synergistically with abscisic acid (ABA). We identified cis-elements in the Brassica napus napin napA promoter mediating regulation by ABI3 and ABA, by analyzing substitution mutation constructs of napA in transgenic tobacco plantlets ectopically expressing ABI3. In transient analysis using particle bombardment of tobacco leaf sections, a tetramer of the distB ABRE (abscisic acid-responsive element) mediated transactivation by ABI3 and ABI3-dependent response to ABA, whereas a tetramer of the composite RY/G complex, containing RY repeats and a G-box, mediated only ABA-independent transactivation by ABI3. Deletion of the conserved B2 and B3 domains of ABI3 abolished transactivation of napA by ABI3. The two domains of ABI3 interact with different cis-elements: B2 is necessary for ABA-independent and ABA-dependent activations through the distB ABRE, whereas B3 interacts with the RY/G complex. Thus B2 mediates the interaction of ABI3 with the protein complex at the ABRE. The regulation of napA by ABI3 differs from Em regulation by VP1, in that the B3 domain of ABI3 is essential for the ABA-dependent regulation of napA.

  4. ABA signaling in stress-response and seed development.

    PubMed

    Nakashima, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2013-07-01

    KEY MESSAGE : We review the recent progress on ABA signaling, especially ABA signaling for ABA-dependent gene expression, including the AREB/ABF regulon, SnRK2 protein kinase, 2C-type protein phosphatases and ABA receptors. Drought negatively impacts plant growth and the productivity of crops. Drought causes osmotic stress to organisms, and the osmotic stress causes dehydration in plant cells. Abscisic acid (ABA) is produced under osmotic stress conditions, and it plays an important role in the stress response and tolerance of plants. ABA regulates many genes under osmotic stress conditions. It also regulates gene expression during seed development and germination. The ABA-responsive element (ABRE) is the major cis-element for ABA-responsive gene expression. ABRE-binding protein (AREB)/ABRE-binding factor (ABF) transcription factors (TFs) regulate ABRE-dependent gene expression. Other TFs are also involved in ABA-responsive gene expression. SNF1-related protein kinases 2 are the key regulators of ABA signaling including the AREB/ABF regulon. Recently, ABA receptors and group A 2C-type protein phosphatases were shown to govern the ABA signaling pathway. Moreover, recent studies have suggested that there are interactions between the major ABA signaling pathway and other signaling factors in stress-response and seed development. The control of the expression of ABA signaling factors may improve tolerance to environmental stresses.

  5. A novel cold-inducible zinc finger protein from soybean, SCOF-1, enhances cold tolerance in transgenic plants.

    PubMed

    Kim, J C; Lee, S H; Cheong, Y H; Yoo, C M; Lee, S I; Chun, H J; Yun, D J; Hong, J C; Lee, S Y; Lim, C O; Cho, M J

    2001-02-01

    Cold stress on plants induces changes in the transcription of cold response genes. A cDNA clone encoding C2H2-type zinc finger protein, SCOF-1, was isolated from soybean. The transcription of SCOF-1 is specifically induced by low temperature and abscisic acid (ABA) but not by dehydration or high salinity. Constitutive overexpression of SCOF-1 induced cold-regulated (COR) gene expression and enhanced cold tolerance of non-acclimated transgenic Arabidopsis and tobacco plants. SCOF-1 localized to the nucleus but did not bind directly to either C-repeat/dehydration (CRT/DRE) or ABA responsive element (ABRE), cis-acting DNA regulatory elements present in COR gene promoters. However, SCOF-1 greatly enhanced the DNA binding activity of SGBF-1, a soybean G-box binding bZIP transcription factor, to ABRE in vitro. SCOF-1 also interacted with SGBF-1 in a yeast two-hybrid system. The SGBF-1 transactivated the beta-glucuronidase reporter gene driven by the ABRE element in Arabidopsis leaf protoplasts. Furthermore, the SCOF-1 enhanced ABRE-dependent gene expression mediated by SGBF-1. These results suggest that SCOF-1 may function as a positive regulator of COR gene expression mediated by ABRE via protein-protein interaction, which in turn enhances cold tolerance of plants.

  6. Quantitative statistical analysis of cis-regulatory sequences in ABA/VP1- and CBF/DREB1-regulated genes of Arabidopsis.

    PubMed

    Suzuki, Masaharu; Ketterling, Matthew G; McCarty, Donald R

    2005-09-01

    We have developed a simple quantitative computational approach for objective analysis of cis-regulatory sequences in promoters of coregulated genes. The program, designated MotifFinder, identifies oligo sequences that are overrepresented in promoters of coregulated genes. We used this approach to analyze promoter sequences of Viviparous1 (VP1)/abscisic acid (ABA)-regulated genes and cold-regulated genes, respectively, of Arabidopsis (Arabidopsis thaliana). We detected significantly enriched sequences in up-regulated genes but not in down-regulated genes. This result suggests that gene activation but not repression is mediated by specific and common sequence elements in promoters. The enriched motifs include several known cis-regulatory sequences as well as previously unidentified motifs. With respect to known cis-elements, we dissected the flanking nucleotides of the core sequences of Sph element, ABA response elements (ABREs), and the C repeat/dehydration-responsive element. This analysis identified the motif variants that may correlate with qualitative and quantitative differences in gene expression. While both VP1 and cold responses are mediated in part by ABA signaling via ABREs, these responses correlate with unique ABRE variants distinguished by nucleotides flanking the ACGT core. ABRE and Sph motifs are tightly associated uniquely in the coregulated set of genes showing a strict dependence on VP1 and ABA signaling. Finally, analysis of distribution of the enriched sequences revealed a striking concentration of enriched motifs in a proximal 200-base region of VP1/ABA and cold-regulated promoters. Overall, each class of coregulated genes possesses a discrete set of the enriched motifs with unique distributions in their promoters that may account for the specificity of gene regulation.

  7. Some Global Policies for Antibiotic Resistance Depend on Legally Binding and Enforceable Commitments.

    PubMed

    Behdinan, Asha; Hoffman, Steven J; Pearcey, Mark

    2015-01-01

    To address the challenge of antibiotic resistance (ABR), the international community must ensure access, conservation and innovation of antibiotics. These goals can be significantly advanced through ten global policies that have been recommended to form part of an international legal agreement. Policies that could be central to this agreement include the establishment of standards, responsible antibiotic use regulations, and strengthening global surveillance systems. Funding for access, mobilizing resources for infrastructure, strengthening infection control practices, and regulating antibiotic marketing could also be helpful if included in a legal agreement. Incentives for innovation could also be included to mobilize support for its implementation. The inclusion of these policies in an international legal agreement could effectively support global collective action towards several ABR policy goals, some of which may depend on it for their achievement. © 2015 American Society of Law, Medicine & Ethics, Inc.

  8. Proteomics and Functional Analyses of Pepper Abscisic Acid–Responsive 1 (ABR1), Which Is Involved in Cell Death and Defense Signaling[C][W

    PubMed Central

    Choi, Du Seok; Hwang, Byung Kook

    2011-01-01

    Abscisic acid (ABA) is a key regulator of plant growth and development, as well as plant defense responses. A high-throughput in planta proteome screen identified the pepper (Capsicum annuum) GRAM (for glucosyltransferases, Rab-like GTPase activators, and myotubularins) domain-containing ABA-RESPONSIVE1 (ABR1), which is highly induced by infection with avirulent Xanthomonas campestris pv vesicatoria and also by treatment with ABA. The GRAM domain is essential for the cell death response and for the nuclear localization of ABR1. ABR1 is required for priming cell death and reactive oxygen species production, as well as ABA-salicylic acid (SA) antagonism. Silencing of ABR1 significantly compromised the hypersensitive response but enhanced bacterial pathogen growth and ABA levels in pepper. High levels of ABA in ABR1-silenced plants antagonized the SA levels induced by pathogen infection. Heterologous transgenic expression of ABR1 in Arabidopsis thaliana conferred enhanced resistance to Pseudomonas syringae pv tomato and Hyaloperonospora arabidopsidis infection. The susceptibility of the Arabidopsis ABR1 putative ortholog mutant, abr1, to these pathogens also supports the involvement of ABR1 in disease resistance. Together, these results reveal ABR1 as a novel negative regulator of ABA signaling and suggest that the nuclear ABR1 pool is essential for the cell death induction associated with ABA-SA antagonism. PMID:21335377

  9. CodY Promotes Sporulation and Enterotoxin Production by Clostridium perfringens Type A Strain SM101.

    PubMed

    Li, Jihong; Freedman, John C; Evans, Daniel R; McClane, Bruce A

    2017-03-01

    Clostridium perfringens type D strains cause enterotoxemia and enteritis in livestock via epsilon toxin production. In type D strain CN3718, CodY was previously shown to increase the level of epsilon toxin production and repress sporulation. C. perfringens type A strains producing C. perfringens enterotoxin (CPE) cause human food poisoning and antibiotic-associated diarrhea. Sporulation is critical for C. perfringens type A food poisoning since spores contribute to transmission and resistance in the harsh food environment and sporulation is essential for CPE production. Therefore, the current study asked whether CodY also regulates sporulation and CPE production in SM101, a derivative of C. perfringens type A food-poisoning strain NCTC8798. An isogenic codY -null mutant of SM101 showed decreased levels of spore formation, along with lower levels of CPE production. A complemented strain recovered wild-type levels of both sporulation and CPE production. When this result was coupled with the earlier results obtained with CN3718, it became apparent that CodY regulation of sporulation varies among different C. perfringens strains. Results from quantitative reverse transcriptase PCR analysis clearly demonstrated that, during sporulation, codY transcript levels remained high in SM101 but rapidly declined in CN3718. In addition, abrB gene expression patterns varied significantly between codY -null mutants of SM101 and CN3718. Compared to the levels in their wild-type parents, the level of abrB gene expression decreased in the CN3718 codY -null mutant strain but significantly increased in the SM101 codY -null mutant strain, demonstrating CodY-dependent regulation differences in abrB expression between these two strains. This difference appears to be important since overexpression of the abrB gene in SM101 reduced the levels of sporulation and enterotoxin production, supporting the involvement of AbrB repression in regulating C. perfringens sporulation. Copyright © 2017 American Society for Microbiology.

  10. CodY Promotes Sporulation and Enterotoxin Production by Clostridium perfringens Type A Strain SM101

    PubMed Central

    Li, Jihong; Freedman, John C.; Evans, Daniel R.

    2017-01-01

    ABSTRACT Clostridium perfringens type D strains cause enterotoxemia and enteritis in livestock via epsilon toxin production. In type D strain CN3718, CodY was previously shown to increase the level of epsilon toxin production and repress sporulation. C. perfringens type A strains producing C. perfringens enterotoxin (CPE) cause human food poisoning and antibiotic-associated diarrhea. Sporulation is critical for C. perfringens type A food poisoning since spores contribute to transmission and resistance in the harsh food environment and sporulation is essential for CPE production. Therefore, the current study asked whether CodY also regulates sporulation and CPE production in SM101, a derivative of C. perfringens type A food-poisoning strain NCTC8798. An isogenic codY-null mutant of SM101 showed decreased levels of spore formation, along with lower levels of CPE production. A complemented strain recovered wild-type levels of both sporulation and CPE production. When this result was coupled with the earlier results obtained with CN3718, it became apparent that CodY regulation of sporulation varies among different C. perfringens strains. Results from quantitative reverse transcriptase PCR analysis clearly demonstrated that, during sporulation, codY transcript levels remained high in SM101 but rapidly declined in CN3718. In addition, abrB gene expression patterns varied significantly between codY-null mutants of SM101 and CN3718. Compared to the levels in their wild-type parents, the level of abrB gene expression decreased in the CN3718 codY-null mutant strain but significantly increased in the SM101 codY-null mutant strain, demonstrating CodY-dependent regulation differences in abrB expression between these two strains. This difference appears to be important since overexpression of the abrB gene in SM101 reduced the levels of sporulation and enterotoxin production, supporting the involvement of AbrB repression in regulating C. perfringens sporulation. PMID:28052992

  11. Insights into the nature of DNA binding of AbrB-like transcription factors

    PubMed Central

    Sullivan, Daniel M.; Bobay, Benjamin G.; Kojetin, Douglas J.; Thompson, Richele J.; Rance, Mark; Strauch, Mark A.; Cavanagh, John

    2008-01-01

    Summary Understanding the DNA recognition and binding by the AbrB-like family of transcriptional regulators is of significant interest since these proteins enable bacteria to elicit the appropriate response to diverse environmental stimuli. Although these ‘transition-state regulator’ proteins have been well characterized at the genetic level, the general and specific mechanisms of DNA binding remain elusive. We present RDC-refined NMR solution structures and dynamic properties of the DNA-binding domains of three Bacillus subtilis transition-state regulators AbrB, Abh, and SpoVT. We combined previously investigated DNase I footprinting, DNA methylation, gel shift assays, mutagenic and NMR studies to generate a structural model of the complex between AbrBN55 and its cognate promoter, abrB8. These investigations have enabled us to generate the first model for the specific nature of the transition-state regulator-DNA interaction. PMID:19000822

  12. Abscisic acid and stress signals induce Viviparous1 expression in seed and vegetative tissues of maize.

    PubMed

    Cao, Xueyuan; Costa, Liliana M; Biderre-Petit, Corinne; Kbhaya, Bouchab; Dey, Nrisingha; Perez, Pascual; McCarty, Donald R; Gutierrez-Marcos, Jose F; Becraft, Philip W

    2007-02-01

    Viviparous1 (Vp1) encodes a B3 domain-containing transcription factor that is a key regulator of seed maturation in maize (Zea mays). However, the mechanisms of Vp1 regulation are not well understood. To examine physiological factors that may regulate Vp1 expression, transcript levels were monitored in maturing embryos placed in culture under different conditions. Expression of Vp1 decreased after culture in hormone-free medium, but was induced by salinity or osmotic stress. Application of exogenous abscisic acid (ABA) also induced transcript levels within 1 h in a dose-dependent manner. The Vp1 promoter fused to beta-glucuronidase or green fluorescent protein reproduced the endogenous Vp1 expression patterns in transgenic maize plants and also revealed previously unknown expression domains of Vp1. The Vp1 promoter is active in the embryo and aleurone cells of developing seeds and, upon drought stress, was also found in phloem cells of vegetative tissues, including cobs, leaves, and stems. Sequence analysis of the Vp1 promoter identified a potential ABA-responsive complex, consisting of an ACGT-containing ABA response element (ABRE) and a coupling element 1-like motif. Electrophoretic mobility shift assay confirmed that the ABRE and putative coupling element 1 components specifically bound proteins in embryo nuclear protein extracts. Treatment of embryos in hormone-free Murashige and Skoog medium blocked the ABRE-protein interaction, whereas exogenous ABA or mannitol treatment restored this interaction. Our data support a model for a VP1-dependent positive feedback mechanism regulating Vp1 expression during seed maturation.

  13. The Arabidopsis NAC Transcription Factor ANAC096 Cooperates with bZIP-Type Transcription Factors in Dehydration and Osmotic Stress Responses[W

    PubMed Central

    Xu, Zheng-Yi; Kim, Soo Youn; Hyeon, Do Young; Kim, Dae Heon; Dong, Ting; Park, Youngmin; Jin, Jing Bo; Joo, Se-Hwan; Kim, Seong-Ki; Hong, Jong Chan; Hwang, Daehee; Hwang, Inhwan

    2013-01-01

    Multiple transcription factors (TFs) play essential roles in plants under abiotic stress, but how these multiple TFs cooperate in abiotic stress responses remains largely unknown. In this study, we provide evidence that the NAC (for NAM, ATAF1/2, and CUC2) TF ANAC096 cooperates with the bZIP-type TFs ABRE binding factor and ABRE binding protein (ABF/AREB) to help plants survive under dehydration and osmotic stress conditions. ANAC096 directly interacts with ABF2 and ABF4, but not with ABF3, both in vitro and in vivo. ANAC096 and ABF2 synergistically activate RD29A transcription. Our genome-wide gene expression analysis revealed that a major proportion of abscisic acid (ABA)–responsive genes are under the transcriptional regulation of ANAC096. We found that the Arabidopsis thaliana anac096 mutant is hyposensitive to exogenous ABA and shows impaired ABA-induced stomatal closure and increased water loss under dehydration stress conditions. Furthermore, we found the anac096 abf2 abf4 triple mutant is much more sensitive to dehydration and osmotic stresses than the anac096 single mutant or the abf2 abf4 double mutant. Based on these results, we propose that ANAC096 is involved in a synergistic relationship with a subset of ABFs for the transcriptional activation of ABA-inducible genes in response to dehydration and osmotic stresses. PMID:24285786

  14. Transcriptional regulation of ABI3- and ABA-responsive genes including RD29B and RD29A in seeds, germinating embryos, and seedlings of Arabidopsis.

    PubMed

    Nakashima, Kazuo; Fujita, Yasunari; Katsura, Koji; Maruyama, Kyonoshin; Narusaka, Yoshihiro; Seki, Motoaki; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2006-01-01

    ABA-responsive elements (ABREs) are cis-acting elements and basic leucine zipper (bZIP)-type ABRE-binding proteins (AREBs) are transcriptional activators that function in the expression of RD29B in vegetative tissue of Arabidopsis in response to abscisic acid (ABA) treatment. Dehydration-responsive elements (DREs) function as coupling elements of ABRE in the expression of RD29A in response to ABA. Expression analysis using abi3 and abi5 mutants showed that ABI3 and ABI5 play important roles in the expression of RD29B in seeds. Base-substitution analysis showed that two ABREs function strongly and one ABRE coupled with DRE functions weakly in the expression of RD29A in embryos. In a transient transactivation experiment, ABI3, ABI5 and AREB1 activated transcription of a GUS reporter gene driven by the RD29B promoter strongly but these proteins activated the transcription driven by the RD29A promoter weakly. In 35S::ABI3 Arabidopsis plants, the expression of RD29B was up-regulated strongly, but that of RD29A was up-regulated weakly. These results indicate that the expression of RD29B having ABREs in the promoter is up-regulated strongly by ABI3, whereas that of RD29A having one ABRE coupled with DREs in the promoter is up-regulated weakly by ABI3. We compared the expression of 7000 Arabidopsis genes in response to ABA treatment during germination and in the vegetative growth stage, and that in 35S::ABI3 plants using a full-length cDNA microarray. The expression of ABI3- and/or ABA-responsive genes and cis-elements in the promoters are discussed.

  15. [Regulation of sporulation by two-component system YvcPQ in Bacillus thuringiensis].

    PubMed

    Fan, Qingyun; Zhang, Shumeng; Gong, Yujing; He, Jin

    2017-01-04

    To study the regulation of sporulation controlled by two-component system (TCS) YvcPQ. β-galactosidase experiment was used to verify the regulation of YvcP on kapD expression; bacterial one-hybrid assay, EMSA and RT-qPCR were applied to study the regulation of AbrB on yvcPQ expression; markerless gene deletion coupled with spore count was used to reveal the influence of yvcPQ and kapD expressions on sporulation. transcriptional regulator AbrB up-regulated the expression of yvcPQ; YvcP promoted the expression of kapD to inhibit sporulation. AbrB up-regulated the transcription of yvcPQ operon, then the increased YvcP strengthened the transcriptional acitivation of sporulation inhibitor gene kapD, and subsequently inhibited sporulation.

  16. Functional modeling of the human auditory brainstem response to broadband stimulationa)

    PubMed Central

    Verhulst, Sarah; Bharadwaj, Hari M.; Mehraei, Golbarg; Shera, Christopher A.; Shinn-Cunningham, Barbara G.

    2015-01-01

    Population responses such as the auditory brainstem response (ABR) are commonly used for hearing screening, but the relationship between single-unit physiology and scalp-recorded population responses are not well understood. Computational models that integrate physiologically realistic models of single-unit auditory-nerve (AN), cochlear nucleus (CN) and inferior colliculus (IC) cells with models of broadband peripheral excitation can be used to simulate ABRs and thereby link detailed knowledge of animal physiology to human applications. Existing functional ABR models fail to capture the empirically observed 1.2–2 ms ABR wave-V latency-vs-intensity decrease that is thought to arise from level-dependent changes in cochlear excitation and firing synchrony across different tonotopic sections. This paper proposes an approach where level-dependent cochlear excitation patterns, which reflect human cochlear filter tuning parameters, drive AN fibers to yield realistic level-dependent properties of the ABR wave-V. The number of free model parameters is minimal, producing a model in which various sources of hearing-impairment can easily be simulated on an individualized and frequency-dependent basis. The model fits latency-vs-intensity functions observed in human ABRs and otoacoustic emissions while maintaining rate-level and threshold characteristics of single-unit AN fibers. The simulations help to reveal which tonotopic regions dominate ABR waveform peaks at different stimulus intensities. PMID:26428802

  17. Rice ABI5-Like1 Regulates Abscisic Acid and Auxin Responses by Affecting the Expression of ABRE-Containing Genes1[W][OA

    PubMed Central

    Yang, Xi; Yang, Ya-Nan; Xue, Liang-Jiao; Zou, Mei-Juan; Liu, Jian-Ying; Chen, Fan; Xue, Hong-Wei

    2011-01-01

    Abscisic acid (ABA) regulates plant development and is crucial for plant responses to biotic and abiotic stresses. Studies have identified the key components of ABA signaling in Arabidopsis (Arabidopsis thaliana), some of which regulate ABA responses by the transcriptional regulation of downstream genes. Here, we report the functional identification of rice (Oryza sativa) ABI5-Like1 (ABL1), which is a basic region/leucine zipper motif transcription factor. ABL1 is expressed in various tissues and is induced by the hormones ABA and indole-3-acetic acid and stress conditions including salinity, drought, and osmotic pressure. The ABL1 deficiency mutant, abl1, shows suppressed ABA responses, and ABL1 expression in the Arabidopsis abi5 mutant rescued the ABA sensitivity. The ABL1 protein is localized to the nucleus and can directly bind ABA-responsive elements (ABREs; G-box) in vitro. A gene expression analysis by DNA chip hybridization confirms that a large proportion of down-regulated genes of abl1 are involved in stress responses, consistent with the transcriptional activating effects of ABL1. Further studies indicate that ABL1 regulates the plant stress responses by regulating a series of ABRE-containing WRKY family genes. In addition, the abl1 mutant is hypersensitive to exogenous indole-3-acetic acid, and some ABRE-containing genes related to auxin metabolism or signaling are altered under ABL1 deficiency, suggesting that ABL1 modulates ABA and auxin responses by directly regulating the ABRE-containing genes. PMID:21546455

  18. ABrIL - Advanced Brain Imaging Lab : a cloud based computation environment for cooperative neuroimaging projects.

    PubMed

    Neves Tafula, Sérgio M; Moreira da Silva, Nádia; Rozanski, Verena E; Silva Cunha, João Paulo

    2014-01-01

    Neuroscience is an increasingly multidisciplinary and highly cooperative field where neuroimaging plays an important role. Neuroimaging rapid evolution is demanding for a growing number of computing resources and skills that need to be put in place at every lab. Typically each group tries to setup their own servers and workstations to support their neuroimaging needs, having to learn from Operating System management to specific neuroscience software tools details before any results can be obtained from each setup. This setup and learning process is replicated in every lab, even if a strong collaboration among several groups is going on. In this paper we present a new cloud service model - Brain Imaging Application as a Service (BiAaaS) - and one of its implementation - Advanced Brain Imaging Lab (ABrIL) - in the form of an ubiquitous virtual desktop remote infrastructure that offers a set of neuroimaging computational services in an interactive neuroscientist-friendly graphical user interface (GUI). This remote desktop has been used for several multi-institution cooperative projects with different neuroscience objectives that already achieved important results, such as the contribution to a high impact paper published in the January issue of the Neuroimage journal. The ABrIL system has shown its applicability in several neuroscience projects with a relatively low-cost, promoting truly collaborative actions and speeding up project results and their clinical applicability.

  19. Genome-wide analysis of ABA-responsive elements ABRE and CE3 reveals divergent patterns in Arabidopsis and rice

    PubMed Central

    Gómez-Porras, Judith L; Riaño-Pachón, Diego Mauricio; Dreyer, Ingo; Mayer, Jorge E; Mueller-Roeber, Bernd

    2007-01-01

    Background In plants, complex regulatory mechanisms are at the core of physiological and developmental processes. The phytohormone abscisic acid (ABA) is involved in the regulation of various such processes, including stomatal closure, seed and bud dormancy, and physiological responses to cold, drought and salinity stress. The underlying tissue or plant-wide control circuits often include combinatorial gene regulatory mechanisms and networks that we are only beginning to unravel with the help of new molecular tools. The increasing availability of genomic sequences and gene expression data enables us to dissect ABA regulatory mechanisms at the individual gene expression level. In this paper we used an in-silico-based approach directed towards genome-wide prediction and identification of specific features of ABA-responsive elements. In particular we analysed the genome-wide occurrence and positional arrangements of two well-described ABA-responsive cis-regulatory elements (CREs), ABRE and CE3, in thale cress (Arabidopsis thaliana) and rice (Oryza sativa). Results Our results show that Arabidopsis and rice use the ABA-responsive elements ABRE and CE3 distinctively. Earlier reports for various monocots have identified CE3 as a coupling element (CE) associated with ABRE. Surprisingly, we found that while ABRE is equally abundant in both species, CE3 is practically absent in Arabidopsis. ABRE-ABRE pairs are common in both genomes, suggesting that these can form functional ABA-responsive complexes (ABRCs) in Arabidopsis and rice. Furthermore, we detected distinct combinations, orientation patterns and DNA strand preferences of ABRE and CE3 motifs in rice gene promoters. Conclusion Our computational analyses revealed distinct recruitment patterns of ABA-responsive CREs in upstream sequences of Arabidopsis and rice. The apparent absence of CE3s in Arabidopsis suggests that another CE pairs with ABRE to establish a functional ABRC capable of interacting with transcription factors. Further studies will be needed to test whether the observed differences are extrapolatable to monocots and dicots in general, and to understand how they contribute to the fine-tuning of the hormonal response. The outcome of our investigation can now be used to direct future experimentation designed to further dissect the ABA-dependent regulatory networks. PMID:17672917

  20. Genome-wide analysis of ABA-responsive elements ABRE and CE3 reveals divergent patterns in Arabidopsis and rice.

    PubMed

    Gómez-Porras, Judith L; Riaño-Pachón, Diego Mauricio; Dreyer, Ingo; Mayer, Jorge E; Mueller-Roeber, Bernd

    2007-08-01

    In plants, complex regulatory mechanisms are at the core of physiological and developmental processes. The phytohormone abscisic acid (ABA) is involved in the regulation of various such processes, including stomatal closure, seed and bud dormancy, and physiological responses to cold, drought and salinity stress. The underlying tissue or plant-wide control circuits often include combinatorial gene regulatory mechanisms and networks that we are only beginning to unravel with the help of new molecular tools. The increasing availability of genomic sequences and gene expression data enables us to dissect ABA regulatory mechanisms at the individual gene expression level. In this paper we used an in-silico-based approach directed towards genome-wide prediction and identification of specific features of ABA-responsive elements. In particular we analysed the genome-wide occurrence and positional arrangements of two well-described ABA-responsive cis-regulatory elements (CREs), ABRE and CE3, in thale cress (Arabidopsis thaliana) and rice (Oryza sativa). Our results show that Arabidopsis and rice use the ABA-responsive elements ABRE and CE3 distinctively. Earlier reports for various monocots have identified CE3 as a coupling element (CE) associated with ABRE. Surprisingly, we found that while ABRE is equally abundant in both species, CE3 is practically absent in Arabidopsis. ABRE-ABRE pairs are common in both genomes, suggesting that these can form functional ABA-responsive complexes (ABRCs) in Arabidopsis and rice. Furthermore, we detected distinct combinations, orientation patterns and DNA strand preferences of ABRE and CE3 motifs in rice gene promoters. Our computational analyses revealed distinct recruitment patterns of ABA-responsive CREs in upstream sequences of Arabidopsis and rice. The apparent absence of CE3s in Arabidopsis suggests that another CE pairs with ABRE to establish a functional ABRC capable of interacting with transcription factors. Further studies will be needed to test whether the observed differences are extrapolatable to monocots and dicots in general, and to understand how they contribute to the fine-tuning of the hormonal response. The outcome of our investigation can now be used to direct future experimentation designed to further dissect the ABA-dependent regulatory networks.

  1. Small regulatory RNA-induced growth rate heterogeneity of Bacillus subtilis.

    PubMed

    Mars, Ruben A T; Nicolas, Pierre; Ciccolini, Mariano; Reilman, Ewoud; Reder, Alexander; Schaffer, Marc; Mäder, Ulrike; Völker, Uwe; van Dijl, Jan Maarten; Denham, Emma L

    2015-03-01

    Isogenic bacterial populations can consist of cells displaying heterogeneous physiological traits. Small regulatory RNAs (sRNAs) could affect this heterogeneity since they act by fine-tuning mRNA or protein levels to coordinate the appropriate cellular behavior. Here we show that the sRNA RnaC/S1022 from the Gram-positive bacterium Bacillus subtilis can suppress exponential growth by modulation of the transcriptional regulator AbrB. Specifically, the post-transcriptional abrB-RnaC/S1022 interaction allows B. subtilis to increase the cell-to-cell variation in AbrB protein levels, despite strong negative autoregulation of the abrB promoter. This behavior is consistent with existing mathematical models of sRNA action, thus suggesting that induction of protein expression noise could be a new general aspect of sRNA regulation. Importantly, we show that the sRNA-induced diversity in AbrB levels generates heterogeneity in growth rates during the exponential growth phase. Based on these findings, we hypothesize that the resulting subpopulations of fast- and slow-growing B. subtilis cells reflect a bet-hedging strategy for enhanced survival of unfavorable conditions.

  2. Specificity determinants for the abscisic acid response element.

    PubMed

    Sarkar, Aditya Kumar; Lahiri, Ansuman

    2013-01-01

    Abscisic acid (ABA) response elements (ABREs) are a group of cis-acting DNA elements that have been identified from promoter analysis of many ABA-regulated genes in plants. We are interested in understanding the mechanism of binding specificity between ABREs and a class of bZIP transcription factors known as ABRE binding factors (ABFs). In this work, we have modeled the homodimeric structure of the bZIP domain of ABRE binding factor 1 from Arabidopsis thaliana (AtABF1) and studied its interaction with ACGT core motif-containing ABRE sequences. We have also examined the variation in the stability of the protein-DNA complex upon mutating ABRE sequences using the protein design algorithm FoldX. The high throughput free energy calculations successfully predicted the ability of ABF1 to bind to alternative core motifs like GCGT or AAGT and also rationalized the role of the flanking sequences in determining the specificity of the protein-DNA interaction.

  3. Forward Masking of the Speech-Evoked Auditory Brainstem Response.

    PubMed

    Hodge, Sarah E; Menezes, Denise C; Brown, Kevin D; Grose, John H

    2018-02-01

    The hypothesis tested was that forward masking of the speech-evoked auditory brainstem response (sABR) increases peak latency as an inverse function of masker-signal interval (Δt), and that the overall persistence of forward masking is age dependent. Older listeners exhibit deficits in forward masking. If forward-masked sABRs provide an objective measure of the susceptibility of speech sounds to prior stimulation, then this provides a novel approach to examining the age dependence of temporal processing. A /da/ stimulus forward masked by speech-shaped noise (Δt = 4-64 ms) was used to measure sABRs in 10 younger and nine older participants. Forward masking of subsegments of the /da/ stimulus (Δt = 16 ms) and click trains (Δt = 0-64 ms) was also measured. Forward-masked sABRs from young participants showed an increase in latency with decreasing Δt for the initial peak. Latency shifts for later peaks were smaller and more uniform. None of the peak latencies returned to baseline by Δt = 64 ms. Forward-masked /da/ subsegments showed peak latency shifts that did not depend simply on peak position, while forward-masked click trains showed latency shifts that were dependent on click position. The sABRs from older adults were less robust but confirmed the viability of the approach. Forward masking of the sABR provides an objective measure of the susceptibility of the auditory system to prior stimulation. Failure of recovery functions to return to baseline suggests an interaction between forward masking by the prior masker and temporal effects within the stimulus itself.

  4. Characterization of StABF1, a stress-responsive bZIP transcription factor from Solanum tuberosum L. that is phosphorylated by StCDPK2 in vitro.

    PubMed

    Muñiz García, María Noelia; Giammaria, Verónica; Grandellis, Carolina; Téllez-Iñón, María Teresa; Ulloa, Rita María; Capiati, Daniela Andrea

    2012-04-01

    ABF/AREB bZIP transcription factors mediate plant abiotic stress responses by regulating the expression of stress-related genes. These proteins bind to the abscisic acid (ABA)-responsive element (ABRE), which is the major cis-acting regulatory sequence in ABA-dependent gene expression. In an effort to understand the molecular mechanisms of abiotic stress resistance in cultivated potato (Solanum tuberosum L.), we have cloned and characterized an ABF/AREB-like transcription factor from potato, named StABF1. The predicted protein shares 45-57% identity with A. thaliana ABFs proteins and 96% identity with the S. lycopersicum SlAREB1 and presents all of the distinctive features of ABF/AREB transcription factors. Furthermore, StABF1 is able to bind to the ABRE in vitro. StABF1 gene is induced in response to ABA, drought, salt stress and cold, suggesting that it might be a key regulator of ABA-dependent stress signaling pathways in cultivated potato. StABF1 is phosphorylated in response to ABA and salt stress in a calcium-dependent manner, and we have identified a potato CDPK isoform (StCDPK2) that phosphorylates StABF1 in vitro. Interestingly, StABF1 expression is increased during tuber development and by tuber-inducing conditions (high sucrose/nitrogen ratio) in leaves. We also found that StABF1 calcium-dependent phosphorylation is stimulated by tuber-inducing conditions and inhibited by gibberellic acid, which inhibits tuberization.

  5. Abscisic acid-activated SNRK2 protein kinases function in the gene-regulation pathway of ABA signal transduction by phosphorylating ABA response element-binding factors.

    PubMed

    Kobayashi, Yuhko; Murata, Michiharu; Minami, Hideyuki; Yamamoto, Shuhei; Kagaya, Yasuaki; Hobo, Tokunori; Yamamoto, Akiko; Hattori, Tsukaho

    2005-12-01

    The plant hormone abscisic acid (ABA) induces gene expression via the ABA-response element (ABRE) present in the promoters of ABA-regulated genes. A group of bZIP proteins have been identified as ABRE-binding factors (ABFs) that activate transcription through this cis element. A rice ABF, TRAB1, has been shown to be activated via ABA-dependent phosphorylation. While a large number of signalling factors have been identified that are involved in stomatal regulation by ABA, relatively less is known about the ABA-signalling pathway that leads to gene expression. We have shown recently that three members of the rice SnRK2 protein kinase family, SAPK8, SAPK9 and SAPK10, are activated by ABA signal as well as by hyperosmotic stress. Here we show that transient overexpression in cultured cell protoplasts of these ABA-activated SnRK2 protein kinases leads to the activation of an ABRE-regulated promoter, suggesting that these kinases are involved in the gene-regulation pathway of ABA signalling. We further show several lines of evidence that these ABA-activated SnRK2 protein kinases directly phosphorylate TRAB1 in response to ABA. Kinetic analysis of SAPK10 activation and TRAB1 phosphorylation indicated that the latter immediately followed the former. TRAB1 was found to be phosphorylated not only in response to ABA, but also in response to hyperosmotic stress, which was interpreted as the consequence of phosphorylation of TRAB1 by hyperosmotically activated SAPKs. Physical interaction between TRAB1 and SAPK10 in vivo was demonstrated by a co-immunoprecipitation experiment. Finally, TRAB1 was phosphorylated in vitro by the ABA-activated SnRK2 protein kinases at Ser102, which is phosphorylated in vivo in response to ABA and is critical for the activation function.

  6. The transcriptional regulatory network in the drought response and its crosstalk in abiotic stress responses including drought, cold, and heat.

    PubMed

    Nakashima, Kazuo; Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

    2014-01-01

    Drought negatively impacts plant growth and the productivity of crops around the world. Understanding the molecular mechanisms in the drought response is important for improvement of drought tolerance using molecular techniques. In plants, abscisic acid (ABA) is accumulated under osmotic stress conditions caused by drought, and has a key role in stress responses and tolerance. Comprehensive molecular analyses have shown that ABA regulates the expression of many genes under osmotic stress conditions, and the ABA-responsive element (ABRE) is the major cis-element for ABA-responsive gene expression. Transcription factors (TFs) are master regulators of gene expression. ABRE-binding protein and ABRE-binding factor TFs control gene expression in an ABA-dependent manner. SNF1-related protein kinases 2, group A 2C-type protein phosphatases, and ABA receptors were shown to control the ABA signaling pathway. ABA-independent signaling pathways such as dehydration-responsive element-binding protein TFs and NAC TFs are also involved in stress responses including drought, heat, and cold. Recent studies have suggested that there are interactions between the major ABA signaling pathway and other signaling factors in stress responses. The important roles of these TFs in crosstalk among abiotic stress responses will be discussed. Control of ABA or stress signaling factor expression can improve tolerance to environmental stresses. Recent studies using crops have shown that stress-specific overexpression of TFs improves drought tolerance and grain yield compared with controls in the field.

  7. Isolation and functional characterisation of two new bZIP maize regulators of the ABA responsive gene rab28.

    PubMed

    Nieva, Claudia; Busk, Peter K; Domínguez-Puigjaner, Eva; Lumbreras, Victoria; Testillano, Pilar S; Risueño, Maria-Carmen; Pagès, Montserrat

    2005-08-01

    The plant hormone abscisic acid regulates gene expression in response to growth stimuli and abiotic stress. Previous studies have implicated members of the bZIP family of transcription factors as mediators of abscisic acid dependent gene expression through the ABRE cis-element. Here, we identify two new maize bZIP transcription factors, EmBP-2 and ZmBZ-1 related to EmBP-1 and OsBZ-8 families. They are differentially expressed during embryo development; EmBP-2 is constitutive, whereas ZmBZ-1 is abscisic acid-inducible and accumulates during late embryogenesis. Both factors are nuclear proteins that bind to ABREs and activate transcription of the abscisic acid-inducible gene rab28 from maize. EmBP-2 and ZmBZ-1 are phosphorylated by protein kinase CK2 and phosphorylation alters their DNA binding properties. Our data suggest that EmBP-2 and ZmBZ-1 are involved in the expression of abscisic acid inducible genes such as rab28 and their activity is modulated by ABA and by phosphorylation.

  8. Prevalence of antibiotic resistance genes in bacterial communities associated with Cladophora glomerata mats along the nearshore of Lake Ontario.

    PubMed

    Ibsen, Michael; Fernando, Dinesh M; Kumar, Ayush; Kirkwood, Andrea E

    2017-05-01

    The alga Cladophora glomerata can erupt in nuisance blooms throughout the lower Great Lakes. Since bacterial abundance increases with the emergence and decay of Cladophora, we investigated the prevalence of antibiotic resistance (ABR) in Cladophora-associated bacterial communities up-gradient and down-gradient from a large sewage treatment plant (STP) on Lake Ontario. Although STPs are well-known sources of ABR, we also expected detectable ABR from up-gradient wetland communities, since they receive surface run-off from urban and agricultural sources. Statistically significant differences in aquatic bacterial abundance and ABR were found between down-gradient beach samples and up-gradient coastal wetland samples (ANOVA, Holm-Sidak test, p < 0.05). Decaying and free-floating Cladophora sampled near the STP had the highest bacterial densities overall, including on ampicillin- and vancomycin-treated plates. However, quantitative polymerase chain reaction analysis of the ABR genes ampC, tetA, tetB, and vanA from environmental communities showed a different pattern. Some of the highest ABR gene levels occurred at the 2 coastal wetland sites (vanA). Overall, bacterial ABR profiles from environmental samples were distinguishable between living and decaying Cladophora, inferring that Cladophora may control bacterial ABR depending on its life-cycle stage. Our results also show how spatially and temporally dynamic ABR is in nearshore aquatic bacteria, which warrants further research.

  9. Auditory brainstem response to complex sounds: a tutorial

    PubMed Central

    Skoe, Erika; Kraus, Nina

    2010-01-01

    This tutorial provides a comprehensive overview of the methodological approach to collecting and analyzing auditory brainstem responses to complex sounds (cABRs). cABRs provide a window into how behaviorally relevant sounds such as speech and music are processed in the brain. Because temporal and spectral characteristics of sounds are preserved in this subcortical response, cABRs can be used to assess specific impairments and enhancements in auditory processing. Notably, subcortical function is neither passive nor hardwired but dynamically interacts with higher-level cognitive processes to refine how sounds are transcribed into neural code. This experience-dependent plasticity, which can occur on a number of time scales (e.g., life-long experience with speech or music, short-term auditory training, online auditory processing), helps shape sensory perception. Thus, by being an objective and non-invasive means for examining cognitive function and experience-dependent processes in sensory activity, cABRs have considerable utility in the study of populations where auditory function is of interest (e.g., auditory experts such as musicians, persons with hearing loss, auditory processing and language disorders). This tutorial is intended for clinicians and researchers seeking to integrate cABRs into their clinical and/or research programs. PMID:20084007

  10. ABFs, a family of ABA-responsive element binding factors.

    PubMed

    Choi, H; Hong, J; Ha, J; Kang, J; Kim, S Y

    2000-01-21

    Abscisic acid (ABA) plays an important role in environmental stress responses of higher plants during vegetative growth. One of the ABA-mediated responses is the induced expression of a large number of genes, which is mediated by cis-regulatory elements known as abscisic acid-responsive elements (ABREs). Although a number of ABRE binding transcription factors have been known, they are not specifically from vegetative tissues under induced conditions. Considering the tissue specificity of ABA signaling pathways, factors mediating ABA-dependent stress responses during vegetative growth phase may thus have been unidentified so far. Here, we report a family of ABRE binding factors isolated from young Arabidopsis plants under stress conditions. The factors, isolated by a yeast one-hybrid system using a prototypical ABRE and named as ABFs (ABRE binding factors) belong to a distinct subfamily of bZIP proteins. Binding site selection assay performed with one ABF showed that its preferred binding site is the strong ABRE, CACGTGGC. ABFs can transactivate an ABRE-containing reporter gene in yeast. Expression of ABFs is induced by ABA and various stress treatments, whereas their induction patterns are different from one another. Thus, a new family of ABRE binding factors indeed exists that have the potential to activate a large number of ABA/stress-responsive genes in Arabidopsis.

  11. Abh and AbrB Control of Bacillus subtilis Antimicrobial Gene Expression▿

    PubMed Central

    Strauch, Mark A.; Bobay, Benjamin G.; Cavanagh, John; Yao, Fude; Wilson, Angelo; Le Breton, Yoann

    2007-01-01

    The Bacillus subtilis abh gene encodes a protein whose N-terminal domain has 74% identity to the DNA-binding domain of the global regulatory protein AbrB. Strains with a mutation in abh showed alterations in the production of antimicrobial compounds directed against some other Bacillus species and gram-positive microbes. Relative to its wild-type parental strain, the abh mutant was found deficient, enhanced, or unaffected for the production of antimicrobial activity. Using lacZ fusions, we examined the effects of abh upon the expression of 10 promoters known to be regulated by AbrB, including five that transcribe well-characterized antimicrobial functions (SdpC, SkfA, TasA, sublancin, and subtilosin). For an otherwise wild-type background, the results show that Abh plays a negative regulatory role in the expression of four of the promoters, a positive role for the expression of three, and no apparent regulatory role in the expression of the other three promoters. Binding of AbrB and Abh to the promoter regions was examined using DNase I footprinting, and the results revealed significant differences. The transcription of abh is not autoregulated, but it is subject to a degree of AbrB-afforded negative regulation. The results indicate that Abh is part of the complex interconnected regulatory system that controls gene expression during the transition from active growth to stationary phase. PMID:17720793

  12. Active Brownian rods

    NASA Astrophysics Data System (ADS)

    Peruani, Fernando

    2016-11-01

    Bacteria, chemically-driven rods, and motility assays are examples of active (i.e. self-propelled) Brownian rods (ABR). The physics of ABR, despite their ubiquity in experimental systems, remains still poorly understood. Here, we review the large-scale properties of collections of ABR moving in a dissipative medium. We address the problem by presenting three different models, of decreasing complexity, which we refer to as model I, II, and III, respectively. Comparing model I, II, and III, we disentangle the role of activity and interactions. In particular, we learn that in two dimensions by ignoring steric or volume exclusion effects, large-scale nematic order seems to be possible, while steric interactions prevent the formation of orientational order at large scales. The macroscopic behavior of ABR results from the interplay between active stresses and local alignment. ABR exhibit, depending on where we locate ourselves in parameter space, a zoology of macroscopic patterns that ranges from polar and nematic bands to dynamic aggregates.

  13. An ABA-responsive DRE-binding protein gene from Setaria italica, SiARDP, the target gene of SiAREB, plays a critical role under drought stress.

    PubMed

    Li, Cong; Yue, Jing; Wu, Xiaowei; Xu, Cong; Yu, Jingjuan

    2014-10-01

    The DREB (dehydration-responsive element binding)-type transcription factors regulate the expression of stress-inducible genes by binding the DRE/CRT cis-elements in promoter regions. The upstream transcription factors that regulate the transcription of DREB transcription factors have not been clearly defined, although the function of DREB transcription factors in abiotic stress is known. In this study, an abscisic acid (ABA)-responsive DREB-binding protein gene (SiARDP) was cloned from foxtail millet (Setaria italica). The transcript level of SiARDP increased not only after drought, high salt, and low temperature stresses, but also after an ABA treatment in foxtail millet seedlings. Two ABA-responsive elements (ABRE1: ACGTGTC; ABRE2: ACGTGGC) exist in the promoter of SiARDP. Further analyses showed that two ABA-responsive element binding (AREB)-type transcription factors, SiAREB1 and SiAREB2, could physically bind to the ABRE core element in vitro and in vivo. The constitutive expression of SiARDP in Arabidopsis thaliana enhanced drought and salt tolerance during seed germination and seedling development, and overexpression of SiARDP in foxtail millet improved drought tolerance. The expression levels of target genes of SiARDP were upregulated in transgenic Arabidopsis and foxtail millet. These results reveal that SiARDP, one of the target genes of SiAREB, is involved in ABA-dependent signal pathways and plays a critical role in the abiotic stress response in plants. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  14. The Physiological Basis and Clinical Use of the Binaural Interaction Component of the Auditory Brainstem Response

    PubMed Central

    Klump, Georg M.; Tollin, Daniel J.

    2016-01-01

    The auditory brainstem response (ABR) is a sound-evoked non-invasively measured electrical potential representing the sum of neuronal activity in the auditory brainstem and midbrain. ABR peak amplitudes and latencies are widely used in human and animal auditory research and for clinical screening. The binaural interaction component (BIC) of the ABR stands for the difference between the sum of the monaural ABRs and the ABR obtained with binaural stimulation. The BIC comprises a series of distinct waves, the largest of which (DN1) has been used for evaluating binaural hearing in both normal hearing and hearing-impaired listeners. Based on data from animal and human studies, we discuss the possible anatomical and physiological bases of the BIC (DN1 in particular). The effects of electrode placement and stimulus characteristics on the binaurally evoked ABR are evaluated. We review how inter-aural time and intensity differences affect the BIC and, analyzing these dependencies, draw conclusion about the mechanism underlying the generation of the BIC. Finally, the utility of the BIC for clinical diagnoses are summarized. PMID:27232077

  15. Two ABREs, two redundant root-specific and one W-box cis-acting elements are functional in the sunflower HAHB4 promoter.

    PubMed

    Manavella, Pablo A; Dezar, Carlos A; Ariel, Federico D; Chan, Raquel L

    2008-10-01

    HAHB4 is a sunflower gene encoding a homeodomain-leucine zipper (HD-Zip) transcription factor. It was previously demonstrated that this gene is regulated at the transcriptional level by several abiotic factors and hormones. A previous analysis in the PLACE database revealed the presence of four putative ABREs. In this work these four elements and also one W-box and two root-specific expression elements were characterized as functional. Site-directed mutagenesis on the promoter, stable transformation of Arabidopis plants as well as transient transformation of sunflower leaves, were performed. The analysis of the transformants was carried out by histochemistry and real time RT-PCR. The results indicate that just one ABRE out of the four is responsible for ABA, NaCl and drought regulation. However, NaCl induction occurs also by an additional ABA-independent way involving another two overlapped ABREs. On the other hand, it was determined that the W-box located 5' upstream is responsive to ethylene and only two root-specific expression elements, among the several detected, are functional but redundant. Conservation of molecular mechanisms between sunflower and Arabidopsis is strongly supported by this experimental work.

  16. Age-Related Changes in Binaural Interaction at Brainstem Level.

    PubMed

    Van Yper, Lindsey N; Vermeire, Katrien; De Vel, Eddy F J; Beynon, Andy J; Dhooge, Ingeborg J M

    2016-01-01

    Age-related hearing loss hampers the ability to understand speech in adverse listening conditions. This is attributed to a complex interaction of changes in the peripheral and central auditory system. One aspect that may deteriorate across the lifespan is binaural interaction. The present study investigates binaural interaction at the level of the auditory brainstem. It is hypothesized that brainstem binaural interaction deteriorates with advancing age. Forty-two subjects of various age participated in the study. Auditory brainstem responses (ABRs) were recorded using clicks and 500 Hz tone-bursts. ABRs were elicited by monaural right, monaural left, and binaural stimulation. Binaural interaction was investigated in two ways. First, grand averages of the binaural interaction component were computed for each age group. Second, wave V characteristics of the binaural ABR were compared with those of the summed left and right ABRs. Binaural interaction in the click ABR was demonstrated by shorter latencies and smaller amplitudes in the binaural compared with the summed monaural responses. For 500 Hz tone-burst ABR, no latency differences were found. However, amplitudes were significantly smaller in the binaural than summed monaural condition. An age-effect was found for 500 Hz tone-burst, but not for click ABR. Brainstem binaural interaction seems to decline with age. Interestingly, these changes seem to be stimulus-dependent.

  17. The influence of cochlear spectral processing on the timing and amplitude of the speech-evoked auditory brain stem response

    PubMed Central

    Nuttall, Helen E.; Moore, David R.; Barry, Johanna G.; Krumbholz, Katrin

    2015-01-01

    The speech-evoked auditory brain stem response (speech ABR) is widely considered to provide an index of the quality of neural temporal encoding in the central auditory pathway. The aim of the present study was to evaluate the extent to which the speech ABR is shaped by spectral processing in the cochlea. High-pass noise masking was used to record speech ABRs from delimited octave-wide frequency bands between 0.5 and 8 kHz in normal-hearing young adults. The latency of the frequency-delimited responses decreased from the lowest to the highest frequency band by up to 3.6 ms. The observed frequency-latency function was compatible with model predictions based on wave V of the click ABR. The frequency-delimited speech ABR amplitude was largest in the 2- to 4-kHz frequency band and decreased toward both higher and lower frequency bands despite the predominance of low-frequency energy in the speech stimulus. We argue that the frequency dependence of speech ABR latency and amplitude results from the decrease in cochlear filter width with decreasing frequency. The results suggest that the amplitude and latency of the speech ABR may reflect interindividual differences in cochlear, as well as central, processing. The high-pass noise-masking technique provides a useful tool for differentiating between peripheral and central effects on the speech ABR. It can be used for further elucidating the neural basis of the perceptual speech deficits that have been associated with individual differences in speech ABR characteristics. PMID:25787954

  18. Arabidopsis basic leucine zipper transcription factors involved in an abscisic acid-dependent signal transduction pathway under drought and high-salinity conditions

    PubMed Central

    Uno, Yuichi; Furihata, Takashi; Abe, Hiroshi; Yoshida, Riichiro; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2000-01-01

    The induction of the dehydration-responsive Arabidopsis gene, rd29B, is mediated mainly by abscisic acid (ABA). Promoter analysis of rd29B indicated that two ABA-responsive elements (ABREs) are required for the dehydration-responsive expression of rd29B as cis-acting elements. Three cDNAs encoding basic leucine zipper (bZIP)-type ABRE-binding proteins were isolated by using the yeast one-hybrid system and were designated AREB1, AREB2, and AREB3 (ABA-responsive element binding protein). Transcription of the AREB1 and AREB2 genes is up-regulated by drought, NaCl, and ABA treatment in vegetative tissues. In a transient transactivation experiment using Arabidopsis leaf protoplasts, both the AREB1 and AREB2 proteins activated transcription of a reporter gene driven by ABRE. AREB1 and AREB2 required ABA for their activation, because their transactivation activities were repressed in aba2 and abi1 mutants and enhanced in an era1 mutant. Activation of AREBs by ABA was suppressed by protein kinase inhibitors. These results suggest that both AREB1 and AREB2 function as transcriptional activators in the ABA-inducible expression of rd29B, and further that ABA-dependent posttranscriptional activation of AREB1 and AREB2, probably by phosphorylation, is necessary for their maximum activation by ABA. Using cultured Arabidopsis cells, we demonstrated that a specific ABA-activated protein kinase of 42-kDa phosphorylated conserved N-terminal regions in the AREB proteins. PMID:11005831

  19. Arabidopsis basic leucine zipper transcription factors involved in an abscisic acid-dependent signal transduction pathway under drought and high-salinity conditions.

    PubMed

    Uno, Y; Furihata, T; Abe, H; Yoshida, R; Shinozaki, K; Yamaguchi-Shinozaki, K

    2000-10-10

    The induction of the dehydration-responsive Arabidopsis gene, rd29B, is mediated mainly by abscisic acid (ABA). Promoter analysis of rd29B indicated that two ABA-responsive elements (ABREs) are required for the dehydration-responsive expression of rd29B as cis-acting elements. Three cDNAs encoding basic leucine zipper (bZIP)-type ABRE-binding proteins were isolated by using the yeast one-hybrid system and were designated AREB1, AREB2, and AREB3 (ABA-responsive element binding protein). Transcription of the AREB1 and AREB2 genes is up-regulated by drought, NaCl, and ABA treatment in vegetative tissues. In a transient transactivation experiment using Arabidopsis leaf protoplasts, both the AREB1 and AREB2 proteins activated transcription of a reporter gene driven by ABRE. AREB1 and AREB2 required ABA for their activation, because their transactivation activities were repressed in aba2 and abi1 mutants and enhanced in an era1 mutant. Activation of AREBs by ABA was suppressed by protein kinase inhibitors. These results suggest that both AREB1 and AREB2 function as transcriptional activators in the ABA-inducible expression of rd29B, and further that ABA-dependent posttranscriptional activation of AREB1 and AREB2, probably by phosphorylation, is necessary for their maximum activation by ABA. Using cultured Arabidopsis cells, we demonstrated that a specific ABA-activated protein kinase of 42-kDa phosphorylated conserved N-terminal regions in the AREB proteins.

  20. ACGT-containing abscisic acid response element (ABRE) and coupling element 3 (CE3) are functionally equivalent.

    PubMed

    Hobo, T; Asada, M; Kowyama, Y; Hattori, T

    1999-09-01

    ACGT-containing ABA response elements (ABREs) have been functionally identified in the promoters of various genes. In addition, single copies of ABRE have been found to require a cis-acting, coupling element to achieve ABA induction. A coupling element 3 (CE3) sequence, originally identified as such in the barley HVA1 promoter, is found approximately 30 bp downstream of motif A (ACGT-containing ABRE) in the promoter of the Osem gene. The relationship between these two elements was further defined by linker-scan analyses of a 55 bp fragment of the Osem promoter, which is sufficient for ABA-responsiveness and VP1 activation. The analyses revealed that both motif A and CE3 sequence were required not only for ABA-responsiveness but also for VP1 activation. Since the sequences of motif A and CE3 were found to be similar, motif-exchange experiments were carried out. The experiments demonstrated that motif A and CE3 were interchangeable by each other with respect to both ABA and VP1 regulation. In addition, both sequences were shown to be recognized by a VP1-interacting, ABA-responsive bZIP factor TRAB1. These results indicate that ACGT-containing ABREs and CE3 are functionally equivalent cis-acting elements. Furthermore, TRAB1 was shown to bind two other non-ACGT ABREs. Based on these results, all these ABREs including CE3 are proposed to be categorized into a single class of cis-acting elements.

  1. The role of eABR with intracochlear test electrode in decision making between cochlear and brainstem implants: preliminary results.

    PubMed

    Cinar, Betul Cicek; Yarali, Mehmet; Atay, Gamze; Bajin, Munir Demir; Sennaroglu, Gonca; Sennaroglu, Levent

    2017-09-01

    The objective of the study was to discuss the findings of intraoperative electrically evoked auditory brainstem response (eABR) test results with a recently designed intracochlear test electrode (ITE) in terms of their relation to decisions of cochlear or auditory brainstem implantation. This clinical study was conducted in Hacettepe University, Department of Otolaryngology, Head and Neck Surgery and Department of Audiology. Subjects were selected from inner ear malformation (IEM) database. Eleven subjects with profound sensorineural hearing loss were included in the current study with age range from 1 year 3 months to 4 years 3 months for children with prelingual hearing loss. There was only one 42-year-old post-lingual subject. eABR was recorded with an ITE and intraoperatively with an original cochlear implant (CI) electrode in 11 cases with different IEMs. Findings of eABR with ITE and their relation to the decision for CI or auditory brainstem implant (ABI) are discussed. Positive eABR test results were found to be dependent on close to normal cochlear structures and auditory nerve. The probability of positive result decreases with increasing degree of malformation severity. The prediction value of eABR via ITE on decision for hearing restoration was found to be questionable in this study. The results of eABR with ITE have predictive value on what we will get with the actual CI electrode. ITE appears to stimulate the cochlea like an actual CI. If the eABR is positive, the results are reliable. However, if eABR is negative, the results should be evaluated with preoperative audiological testing and MRI findings.

  2. Interaction between two cis-acting elements, ABRE and DRE, in ABA-dependent expression of Arabidopsis rd29A gene in response to dehydration and high-salinity stresses.

    PubMed

    Narusaka, Yoshihiro; Nakashima, Kazuo; Shinwari, Zabta K; Sakuma, Yoh; Furihata, Takashi; Abe, Hiroshi; Narusaka, Mari; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2003-04-01

    Many abiotic stress-inducible genes contain two cis-acting elements, namely a dehydration-responsive element (DRE; TACCGACAT) and an ABA-responsive element (ABRE; ACGTGG/TC), in their promoter regions. We precisely analyzed the 120 bp promoter region (-174 to -55) of the Arabidopsis rd29A gene whose expression is induced by dehydration, high-salinity, low-temperature, and abscisic acid (ABA) treatments and whose 120 bp promoter region contains the DRE, DRE/CRT-core motif (A/GCCGAC), and ABRE sequences. Deletion and base substitution analyses of this region showed that the DRE-core motif functions as DRE and that the DRE/DRE-core motif could be a coupling element of ABRE. Gel mobility shift assays revealed that DRE-binding proteins (DREB1s/CBFs and DREB2s) bind to both DRE and the DRE-core motif and that ABRE-binding proteins (AREBs/ABFs) bind to ABRE in the 120 bp promoter region. In addition, transactivation experiments using Arabidopsis leaf protoplasts showed that DREBs and AREBs cumulatively transactivate the expression of a GUS reporter gene fused to the 120 bp promoter region of rd29A. These results indicate that DRE and ABRE are interdependent in the ABA-responsive expression of the rd29A gene in response to ABA in Arabidopsis.

  3. A distal ABA responsive element in AtNCED3 promoter is required for positive feedback regulation of ABA biosynthesis in Arabidopsis.

    PubMed

    Yang, Yan-Zhuo; Tan, Bao-Cai

    2014-01-01

    The plant hormone abscisic acid (ABA) plays a crucial role in plant development and responses to abiotic stresses. Recent studies indicate that a positive feedback regulation by ABA exists in ABA biosynthesis in plants under dehydration stress. To understand the molecular basis of this regulation, we analyzed the cis-elements of the AtNCED3 promoter in Arabidopsis. AtNCED3 encodes the first committed and highly regulated dioxygenase in the ABA biosynthetic pathway. Through delineated and mutagenesis analyses in stable-transformed Arabidopsis, we revealed that a distal ABA responsive element (ABRE: GGCACGTG, -2372 to -2364 bp) is required for ABA-induced AtNCED3 expression. By analyzing the AtNCED3 expression in ABRE binding protein ABF3 over-expression transgenic plants and knock-out mutants, we provide evidence that the ABA feedback regulation of AtNCED3 expression is not mediated by ABF3.

  4. Expression in Bacillus subtilis of the Bacillus thuringiensis cryIIIA toxin gene is not dependent on a sporulation-specific sigma factor and is increased in a spo0A mutant.

    PubMed

    Agaisse, H; Lereclus, D

    1994-08-01

    Expression of the Bacillus thuringiensis cryIIIA gene encoding a Coleoptera-specific toxin is weak during vegetative growth and is activated at the onset of the stationary phase. cryIIIA'-'lacZ fusions and primer extension analysis show that the regulation of cryIIIA expression is similar in Bacillus subtilis and in B. thuringiensis. Activation of cryIIIA expression was not altered in B. subtilis mutant strains deficient for the sigma H and sigma E sporulation-specific sigma factors or for minor sigma factors such as sigma B, sigma D, or sigma L. This result and the nucleotide sequence of the -35 and -10 regions of the cryIIIA promoter suggest that cryIIIA expression might be directed by the E sigma A form of RNA polymerase. Expression of the cryIIIA'-'lacZ fusion is shut off after t2 (2 h after time zero) of sporulation in the B. subtilis wild-type strain grown on nutrient broth sporulation medium. However, no decrease in cryIIIA-directed beta-galactosidase activity occurred in sigma H, kinA, or spo0A mutant strains. Moreover, beta-galactosidase activity was higher and remained elevated after t2 in the spo0A mutant strain. beta-Galactosidase activity was weak in abrB and spo0A abrB mutant strains, suggesting that AbrB is responsible for the higher level of cryIIIA expression observed in a spo0A mutant. However, both in spo0A and spo0A abrB mutant strains, beta-galactosidase activity remained elevated after t2, suggesting that even in the absence of AbrB, cryIIIA expression is controlled through modulation of the phosphorylated form of Spo0A. When the cryIIIA gene is expressed in a B. subtilis spo0A mutant strain or in the 168 wild-type strain, large amounts of toxins are produced and accumulate to form a flat rectangular crystal characteristic of the coleopteran-specific B. thuringiensis strains.

  5. Transcriptome Analysis of ABA/JA-Dual Responsive Genes in Rice Shoot and Root.

    PubMed

    Kim, Jin-Ae; Bhatnagar, Nikita; Kwon, Soon Jae; Min, Myung Ki; Moon, Seok-Jun; Yoon, In Sun; Kwon, Taek-Ryoun; Kim, Sun Tae; Kim, Beom-Gi

    2018-01-01

    The phytohormone abscisic acid (ABA) enables plants to adapt to adverse environmental conditions through the modulation of metabolic pathways and of growth and developmental programs. We used comparative microarray analysis to identify genes exhibiting ABA-dependent expression and other hormone-dependent expression among them in Oryza sativa shoot and root. We identified 854 genes as significantly up- or down-regulated in root or shoot under ABA treatment condition. Most of these genes had similar expression profiles in root and shoot under ABA treatment condition, whereas 86 genes displayed opposite expression responses in root and shoot. To examine the crosstalk between ABA and other hormones, we compared the expression profiles of the ABA-dependently regulated genes under several different hormone treatment conditions. Interestingly, around half of the ABA-dependently expressed genes were also regulated by jasmonic acid based on microarray data analysis. We searched the promoter regions of these genes for cis-elements that could be responsible for their responsiveness to both hormones, and found that ABRE and MYC2 elements, among others, were common to the promoters of genes that were regulated by both ABA and JA. These results show that ABA and JA might have common gene expression regulation system and might explain why the JA could function for both abiotic and biotic stress tolerance.

  6. Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1).

    PubMed

    Zhao, Minzhi; Li, Haiyun; Ma, Yan; Gong, He; Yang, Shu; Fang, Qiaojun; Hu, Zhiyuan

    2017-01-01

    Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression ( P <0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. Albumin plays a major role in the regulation of this protein. In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. It is also noteworthy that the deficiency of GNA1 might reduce insulin secretion which correlates with type 2 diabetes.

  7. ABR Examinations: The Why, What, and How

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

    Becker, Gary J.; Bosma, Jennifer L., E-mail: jbosma@theabr.org; Guiberteau, Milton J.

    The American Board of Radiology (ABR) has provided certification for diagnostic radiologists and other specialists and subspecialists for more than 75 years. The Board certification process is a tangible expression of the social contract between the profession and the public by which the profession enjoys the privilege of self-regulation and the public is assured that it can expect medical professionals to put patients' interests first, guarantees the competence of practitioners, and guards the public health. A primary tool used by the ABR in fulfilling this responsibility is the secure proctored examination. This article sets forth seven standards based on authoritativemore » sources in the field of psychometrics (the science of mental measurements), and explains in each case how the ABR implements that standard. Readers are encouraged to understand that, despite the multiple opinions that may be held, these standards developed over decades by experts using the scientific method should be the central feature in any discussion or critique of examinations given for the privilege of professional practice and for safeguarding the public well-being.« less

  8. A Distal ABA Responsive Element in AtNCED3 Promoter Is Required for Positive Feedback Regulation of ABA Biosynthesis in Arabidopsis

    PubMed Central

    Yang, Yan-Zhuo; Tan, Bao-Cai

    2014-01-01

    The plant hormone abscisic acid (ABA) plays a crucial role in plant development and responses to abiotic stresses. Recent studies indicate that a positive feedback regulation by ABA exists in ABA biosynthesis in plants under dehydration stress. To understand the molecular basis of this regulation, we analyzed the cis-elements of the AtNCED3 promoter in Arabidopsis. AtNCED3 encodes the first committed and highly regulated dioxygenase in the ABA biosynthetic pathway. Through delineated and mutagenesis analyses in stable-transformed Arabidopsis, we revealed that a distal ABA responsive element (ABRE: GGCACGTG, -2372 to -2364 bp) is required for ABA-induced AtNCED3 expression. By analyzing the AtNCED3 expression in ABRE binding protein ABF3 over-expression transgenic plants and knock-out mutants, we provide evidence that the ABA feedback regulation of AtNCED3 expression is not mediated by ABF3. PMID:24475264

  9. Speech auditory brainstem response (speech ABR) characteristics depending on recording conditions, and hearing status: an experimental parametric study.

    PubMed

    Akhoun, Idrick; Moulin, Annie; Jeanvoine, Arnaud; Ménard, Mikael; Buret, François; Vollaire, Christian; Scorretti, Riccardo; Veuillet, Evelyne; Berger-Vachon, Christian; Collet, Lionel; Thai-Van, Hung

    2008-11-15

    Speech elicited auditory brainstem responses (Speech ABR) have been shown to be an objective measurement of speech processing in the brainstem. Given the simultaneous stimulation and recording, and the similarities between the recording and the speech stimulus envelope, there is a great risk of artefactual recordings. This study sought to systematically investigate the source of artefactual contamination in Speech ABR response. In a first part, we measured the sound level thresholds over which artefactual responses were obtained, for different types of transducers and experimental setup parameters. A watermelon model was used to model the human head susceptibility to electromagnetic artefact. It was found that impedances between the electrodes had a great effect on electromagnetic susceptibility and that the most prominent artefact is due to the transducer's electromagnetic leakage. The only artefact-free condition was obtained with insert-earphones shielded in a Faraday cage linked to common ground. In a second part of the study, using the previously defined artefact-free condition, we recorded speech ABR in unilateral deaf subjects and bilateral normal hearing subjects. In an additional control condition, Speech ABR was recorded with the insert-earphones used to deliver the stimulation, unplugged from the ears, so that the subjects did not perceive the stimulus. No responses were obtained from the deaf ear of unilaterally hearing impaired subjects, nor in the insert-out-of-the-ear condition in all the subjects, showing that Speech ABR reflects the functioning of the auditory pathways.

  10. Achyranthis bidentatae radix enhanced articular distribution and anti-inflammatory effect of berberine in Sanmiao Wan using an acute gouty arthritis rat model.

    PubMed

    Wu, Juan; Li, Jingya; Li, Wei; Sun, Bei; Xie, Jin; Cheng, Wenming; Zhang, Qunlin

    2018-07-15

    Sanmiao Wan (SMW) has been a basic prescription employed for the treatment for gout in the clinic since Yuan dynasty. Achyranthis bidentatae radix (ABR) is designed as a lower-guiding drug in SMW to augment the articular accumulation of active ingredients and improve the anti-inflammatory effect. Present study was undertaken to investigate the dose-response relationship of berberine in SMW between the articular concentration and anti-inflammatory effect in the knee joint under the lower-guiding of ABR. Rats were divided into control group, model group and SMW without or with low, medium and high doses of ABR groups. Rat model of acute gouty arthritis (AGA) was established by intra-articular injection of 0.2 mL monosodium urate crystal (20 mg/mL) inside knee joint cavity on day 2 during drug treatment slots. Knee joint swelling, synovial hyperplasia and inflammatory cell infiltration were investigated for anti-inflammatory study. The concentrations of berberine in rat plasma and tissues were determined by UPLC-MS/MS method. The effect of ABR on the expression levels of P-glycoprotein (P-gp) and MDR1 mRNA in the synovial tissues of knee joints in AGA rats was examined by Western blot and RT-qPCR assay, respectively. The distribution of berberine increased by 6.53%, 44.31% and 212.96% in the knee joint and 474.93%, 631.01% and 1063.3% in the ankle for SMW with low, medium and high doses of ABR groups, compared with SMW without ABR group. Similarly, the plasma level of berberine increased by 19.81%, 143.4% and 681.13%. On the contrary, the distribution of berberine evidently decreased 3.23, 10.61 and 46.21-fold in heart and 3.68, 6.74 and 24.78-fold in lung. SMW with different doses of ABR groups exhibited better efficiency than SMW without ABR group on ameliorating knee joint swelling, inhibiting synovial hyperplasia and alleviating inflammatory cell infiltration of AGA rats. The treatment with ABR could down-regulate the MDR1 mRNA and P-gp expressions of synovial tissues of knee joints in AGA rats. The enhanced articular distribution of berberine in SMW was attributed to the lower-guiding effect of ABR, which could evidently increase the plasma concentration of berberine, improve the supply of blood of inflamed joint, reduce the distribution of berberine in heart and lung and significantly inhibit the MDR1 mRNA and P-gp expression of synovial tissues of knee joints in AGA rats. The dose-response relationship of berberine between the enhanced articular concentration and improved anti-inflammatory effect in the knee joint under the lower-guiding of ABR was observed for the first time. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Organization of cis-acting regulatory elements in osmotic- and cold-stress-responsive promoters.

    PubMed

    Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

    2005-02-01

    cis-Acting regulatory elements are important molecular switches involved in the transcriptional regulation of a dynamic network of gene activities controlling various biological processes, including abiotic stress responses, hormone responses and developmental processes. In particular, understanding regulatory gene networks in stress response cascades depends on successful functional analyses of cis-acting elements. The ever-improving accuracy of transcriptome expression profiling has led to the identification of various combinations of cis-acting elements in the promoter regions of stress-inducible genes involved in stress and hormone responses. Here we discuss major cis-acting elements, such as the ABA-responsive element (ABRE) and the dehydration-responsive element/C-repeat (DRE/CRT), that are a vital part of ABA-dependent and ABA-independent gene expression in osmotic and cold stress responses.

  12. TCP performance in ATM networks: ABR parameter tuning and ABR/UBR comparisons

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

    Chien Fang; Lin, A.

    1996-02-27

    This paper explores two issues on TOP performance over ATM networks: ABR parameter tuning and performance comparison of binary mode ABR with enhanced UBR services. Of the fifteen parameters defined for ABR, two parameters dominate binary mode ABR performance: Rate Increase Factor (RIF) and Rate Decrease Factor (RDF). Using simulations, we study the effects of these two parameters on TOP over ABR performance. We compare TOP performance with different ABR parameter settings in terms of through-puts and fairness. The effects of different buffer sizes and LAN/WAN distances are also examined. We then compare TOP performance with the best ABR parametermore » setting with corresponding UBR service enhanced with Early Packet Discard and also with a fair buffer allocation scheme. The results show that TOP performance over binary mode ABR is very sensitive to parameter value settings, and that a poor choice of parameters can result in ABR performance worse than that of the much less expensive UBR-EPD scheme.« less

  13. In-air hearing of a diving duck: A comparison of psychoacoustic and auditory brainstem response thresholds

    USGS Publications Warehouse

    Crowell, Sara E.; Wells-Berlin, Alicia M.; Therrien, Ronald E.; Yannuzzi, Sally E.; Carr, Catherine E.

    2016-01-01

    Auditory sensitivity was measured in a species of diving duck that is not often kept in captivity, the lesser scaup. Behavioral (psychoacoustics) and electrophysiological [the auditory brainstem response (ABR)] methods were used to measure in-air auditory sensitivity, and the resulting audiograms were compared. Both approaches yielded audiograms with similar U-shapes and regions of greatest sensitivity (2000−3000 Hz). However, ABR thresholds were higher than psychoacoustic thresholds at all frequencies. This difference was least at the highest frequency tested using both methods (5700 Hz) and greatest at 1000 Hz, where the ABR threshold was 26.8 dB higher than the behavioral measure of threshold. This difference is commonly reported in studies involving many different species. These results highlight the usefulness of each method, depending on the testing conditions and availability of the animals.

  14. In-air hearing of a diving duck: A comparison of psychoacoustic and auditory brainstem response thresholds.

    PubMed

    Crowell, Sara E; Wells-Berlin, Alicia M; Therrien, Ronald E; Yannuzzi, Sally E; Carr, Catherine E

    2016-05-01

    Auditory sensitivity was measured in a species of diving duck that is not often kept in captivity, the lesser scaup. Behavioral (psychoacoustics) and electrophysiological [the auditory brainstem response (ABR)] methods were used to measure in-air auditory sensitivity, and the resulting audiograms were compared. Both approaches yielded audiograms with similar U-shapes and regions of greatest sensitivity (2000-3000 Hz). However, ABR thresholds were higher than psychoacoustic thresholds at all frequencies. This difference was least at the highest frequency tested using both methods (5700 Hz) and greatest at 1000 Hz, where the ABR threshold was 26.8 dB higher than the behavioral measure of threshold. This difference is commonly reported in studies involving many different species. These results highlight the usefulness of each method, depending on the testing conditions and availability of the animals.

  15. Isolation and functional characterization of CE1 binding proteins.

    PubMed

    Lee, Sun-ji; Park, Ji Hye; Lee, Mi Hun; Yu, Ji-hyun; Kim, Soo Young

    2010-12-16

    Abscisic acid (ABA) is a plant hormone that controls seed germination, protective responses to various abiotic stresses and seed maturation. The ABA-dependent processes entail changes in gene expression. Numerous genes are regulated by ABA, and promoter analyses of the genes revealed that cis-elements sharing the ACGTGGC consensus sequence are ubiquitous among ABA-regulated gene promoters. The importance of the core sequence, which is generally known as ABA response element (ABRE), has been demonstrated by various experiments, and its cognate transcription factors known as ABFs/AREBs have been identified. Although necessary, ABRE alone is not sufficient, and another cis-element known as "coupling element (CE)" is required for full range ABA-regulation of gene expression. Several CEs are known. However, despite their importance, the cognate transcription factors mediating ABA response via CEs have not been reported to date. Here, we report the isolation of transcription factors that bind one of the coupling elements, CE1. To isolate CE1 binding proteins, we carried out yeast one-hybrid screens. Reporter genes containing a trimer of the CE1 element were prepared and introduced into a yeast strain. The yeast was transformed with library DNA that represents RNA isolated from ABA-treated Arabidopsis seedlings. From the screen of 3.6 million yeast transformants, we isolated 78 positive clones. Analysis of the clones revealed that a group of AP2/ERF domain proteins binds the CE1 element. We investigated their expression patterns and analyzed their overexpression lines to investigate the in vivo functions of the CE element binding factors (CEBFs). Here, we show that one of the CEBFs, AtERF13, confers ABA hypersensitivity in Arabidopsis, whereas two other CEBFs enhance sugar sensitivity. Our results indicate that a group of AP2/ERF superfamily proteins interacts with CE1. Several CEBFs are known to mediate defense or abiotic stress response, but the physiological functions of other CEBFs remain to be determined. Our in vivo functional analysis of several CEBFs suggests that they are likely to be involved in ABA and/or sugar response. Together with previous results reported by others, our current data raise an interesting possibility that the coupling element CE1 may function not only as an ABRE but also as an element mediating biotic and abiotic stress responses.

  16. Transcriptional Regulation of Arabidopsis MIR168a and ARGONAUTE1 Homeostasis in Abscisic Acid and Abiotic Stress Responses1[W

    PubMed Central

    Li, Wei; Cui, Xiao; Meng, Zhaolu; Huang, Xiahe; Xie, Qi; Wu, Heng; Jin, Hailing; Zhang, Dabing; Liang, Wanqi

    2012-01-01

    The accumulation of a number of small RNAs in plants is affected by abscisic acid (ABA) and abiotic stresses, but the underlying mechanisms are poorly understood. The miR168-mediated feedback regulatory loop regulates ARGONAUTE1 (AGO1) homeostasis, which is crucial for gene expression modulation and plant development. Here, we reveal a transcriptional regulatory mechanism by which MIR168 controls AGO1 homeostasis during ABA treatment and abiotic stress responses in Arabidopsis (Arabidopsis thaliana). Plants overexpressing MIR168a and the AGO1 loss-of-function mutant ago1-27 display ABA hypersensitivity and drought tolerance, while the mir168a-2 mutant shows ABA hyposensitivity and drought hypersensitivity. Both the precursor and mature miR168 were induced under ABA and several abiotic stress treatments, but no obvious decrease for the target of miR168, AGO1, was shown under the same conditions. However, promoter activity analysis indicated that AGO1 transcription activity was increased under ABA and drought treatments, suggesting that transcriptional elevation of MIR168a is required for maintaining a stable AGO1 transcript level during the stress response. Furthermore, we showed both in vitro and in vivo that the transcription of MIR168a is directly regulated by four abscisic acid-responsive element (ABRE) binding factors, which bind to the ABRE cis-element within the MIR168a promoter. This ABRE motif is also found in the promoter of MIR168a homologs in diverse plant species. Our findings suggest that transcriptional regulation of miR168 and posttranscriptional control of AGO1 homeostasis may play an important and conserved role in stress response and signal transduction in plants. PMID:22247272

  17. Transcriptional regulation of Arabidopsis MIR168a and argonaute1 homeostasis in abscisic acid and abiotic stress responses.

    PubMed

    Li, Wei; Cui, Xiao; Meng, Zhaolu; Huang, Xiahe; Xie, Qi; Wu, Heng; Jin, Hailing; Zhang, Dabing; Liang, Wanqi

    2012-03-01

    The accumulation of a number of small RNAs in plants is affected by abscisic acid (ABA) and abiotic stresses, but the underlying mechanisms are poorly understood. The miR168-mediated feedback regulatory loop regulates ARGONAUTE1 (AGO1) homeostasis, which is crucial for gene expression modulation and plant development. Here, we reveal a transcriptional regulatory mechanism by which MIR168 controls AGO1 homeostasis during ABA treatment and abiotic stress responses in Arabidopsis (Arabidopsis thaliana). Plants overexpressing MIR168a and the AGO1 loss-of-function mutant ago1-27 display ABA hypersensitivity and drought tolerance, while the mir168a-2 mutant shows ABA hyposensitivity and drought hypersensitivity. Both the precursor and mature miR168 were induced under ABA and several abiotic stress treatments, but no obvious decrease for the target of miR168, AGO1, was shown under the same conditions. However, promoter activity analysis indicated that AGO1 transcription activity was increased under ABA and drought treatments, suggesting that transcriptional elevation of MIR168a is required for maintaining a stable AGO1 transcript level during the stress response. Furthermore, we showed both in vitro and in vivo that the transcription of MIR168a is directly regulated by four abscisic acid-responsive element (ABRE) binding factors, which bind to the ABRE cis-element within the MIR168a promoter. This ABRE motif is also found in the promoter of MIR168a homologs in diverse plant species. Our findings suggest that transcriptional regulation of miR168 and posttranscriptional control of AGO1 homeostasis may play an important and conserved role in stress response and signal transduction in plants.

  18. Binaural interaction in the auditory brainstem response: a normative study.

    PubMed

    Van Yper, Lindsey N; Vermeire, Katrien; De Vel, Eddy F J; Battmer, Rolf-Dieter; Dhooge, Ingeborg J M

    2015-04-01

    Binaural interaction can be investigated using auditory evoked potentials. A binaural interaction component can be derived from the auditory brainstem response (ABR-BIC) and is considered evidence for binaural interaction at the level of the brainstem. Although click ABR-BIC has been investigated thoroughly, data on 500 Hz tone-burst (TB) ABR-BICs are scarce. In this study, characteristics of click and 500 Hz TB ABR-BICs are described. Furthermore, reliability of both click and 500 Hz TB ABR-BIC are investigated. Eighteen normal hearing young adults (eight women, ten men) were included. ABRs were recorded in response to clicks and 500 Hz TBs. ABR-BICs were derived by subtracting the binaural response from the sum of the monaural responses measured in opposite ears. Good inter-rater reliability is obtained for both click and 500 Hz TB ABR-BICs. The most reliable peak in click ABR-BIC occurs at a mean latency of 6.06 ms (SD 0.354 ms). Reliable 500 Hz TB ABR-BIC are obtained with a mean latency of 9.47 ms (SD 0.678 ms). Amplitudes are larger for 500 Hz TB ABR-BIC than for clicks. The most reliable peak in click ABR-BIC occurs at the downslope of wave V. Five hundred Hertz TB ABR-BIC is characterized by a broad positivity occurring at the level of wave V. The ABR-BIC is a useful technique to investigate binaural interaction in certain populations. Examples are bilateral hearing aid users, bilateral cochlear implant users and bimodal listeners. The latter refers to the combination of unilateral cochlear implantation and contralateral residual hearing. The majority of these patients have residual hearing in the low frequencies. The current study suggests that 500 Hz TB ABR-BIC may be a suitable technique to assess binaural interaction in this specific population of cochlear implant users. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Prenatal exposure to multiple pesticides is associated with auditory brainstem response at 9months in a cohort study of Chinese infants.

    PubMed

    Sturza, Julie; Silver, Monica K; Xu, Lin; Li, Mingyan; Mai, Xiaoqin; Xia, Yankai; Shao, Jie; Lozoff, Betsy; Meeker, John

    2016-01-01

    Pesticides are associated with poorer neurodevelopmental outcomes, but little is known about the effects on sensory functioning. Auditory brainstem response (ABR) and pesticide data were available for 27 healthy, full-term 9-month-old infants participating in a larger study of early iron deficiency and neurodevelopment. Cord blood was analyzed by gas chromatography-mass spectrometry for levels of 20 common pesticides. The ABR forward-masking condition consisted of a click stimulus (masker) delivered via ear canal transducers followed by an identical stimulus delayed by 8, 16, or 64 milliseconds (ms). ABR peak latencies were evaluated as a function of masker-stimulus time interval. Shorter wave latencies reflect faster neural conduction, more mature auditory pathways, and greater degree of myelination. Linear regression models were used to evaluate associations between total number of pesticides detected and ABR outcomes. We considered an additive or synergistic effect of poor iron status by stratifying our analysis by newborn ferritin (based on median split). Infants in the sample were highly exposed to pesticides; a mean of 4.1 pesticides were detected (range 0-9). ABR Wave V latency and central conduction time (CCT) were associated with the number of pesticides detected in cord blood for the 64ms and non-masker conditions. A similar pattern seen for CCT from the 8ms and 16ms conditions, although statistical significance was not reached. Increased pesticide exposure was associated with longer latency. The relation between number of pesticides detected in cord blood and CCT depended on the infant's cord blood ferritin level. Specifically, the relation was present in the lower cord blood ferritin group but not the higher cord blood ferritin group. ABR processing was slower in infants with greater prenatal pesticide exposure, indicating impaired neuromaturation. Infants with lower cord blood ferritin appeared to be more sensitive to the effects of prenatal pesticide exposure on ABR latency delay, suggesting an additive or multiplicative effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Prenatal exposure to multiple pesticides is associated with auditory brainstem response at 9 months in a cohort study of Chinese infants

    PubMed Central

    Sturza, Julie; Silver, Monica K.; Xu, Lin; Li, Mingyan; Mai, Xiaoqin; Xia, Yankai; Shao, Jie; Lozoff, Betsy; Meeker, John

    2016-01-01

    Background Pesticides are associated with poorer neurodevelopmental outcomes, but little is known about the effects on sensory functioning. Methods Auditory brainstem response (ABR) and pesticide data were available for 27 healthy, full-term 9-month-old infants participating in a larger study of early iron deficiency and neurodevelopment. Cord blood was analyzed by gas chromatography-mass spectrometry for levels of 20 common pesticides. The ABR forward-masking condition consisted of a click stimulus (masker) delivered via ear canal transducers followed by an identical stimulus delayed by 8, 16, or 64 milliseconds (ms). ABR peak latencies were evaluated as a function of masker-stimulus time interval. Shorter wave latencies reflect faster neural conduction, more mature auditory pathways, and greater degree of myelination. Linear regression models were used to evaluate associations between total number of pesticides detected and ABR outcomes. We considered an additive or synergistic effect of poor iron status by stratifying our analysis by newborn ferritin (based on median split). Results Infants in the sample were highly exposed to pesticides; a mean of 4.1 pesticides were detected (range 0-9). ABR Wave V latency and central conduction time (CCT) were associated with the number of pesticides detected in cord blood for the 64ms and non-masker conditions. A similar pattern seen for CCT from the 8ms and 16ms conditions, although statistical significance was not reached. Increased pesticide exposure was associated with longer latency. The relation between number of pesticides detected in cord blood and CCT depended on the infant’s cord blood ferritin level. Specifically, the relation was present in the lower cord blood ferritin group but not the higher cord blood ferritin group. Conclusions ABR processing was slower in infants with greater prenatal pesticide exposure, indicating impaired neuromaturation. Infants with lower cord blood ferritin appeared to be more sensitive to the effects of prenatal pesticide exposure on ABR latency delay, suggesting an additive or multiplicative effect. PMID:27166702

  1. Abscisic acid-dependent multisite phosphorylation regulates the activity of a transcription activator AREB1.

    PubMed

    Furihata, Takashi; Maruyama, Kyonoshin; Fujita, Yasunari; Umezawa, Taishi; Yoshida, Riichiro; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2006-02-07

    bZIP-type transcription factors AREBs/ABFs bind an abscisic acid (ABA)-responsive cis-acting element named ABRE and transactivate downstream gene expression in Arabidopsis. Because AREB1 overexpression could not induce downstream gene expression, activation of AREB1 requires ABA-dependent posttranscriptional modification. We confirmed that ABA activated 42-kDa kinase activity, which, in turn, phosphorylated Ser/Thr residues of R-X-X-S/T sites in the conserved regions of AREB1. Amino acid substitutions of R-X-X-S/T sites to Ala suppressed transactivation activity, and multiple substitution of these sites resulted in almost complete suppression of transactivation activity in transient assays. In contrast, substitution of the Ser/Thr residues to Asp resulted in high transactivation activity without exogenous ABA application. A phosphorylated, transcriptionally active form was achieved by substitution of Ser/Thr in all conserved R-X-X-S/T sites to Asp. Transgenic plants overexpressing the phosphorylated active form of AREB1 expressed many ABA-inducible genes, such as RD29B, without ABA treatment. These results indicate that the ABA-dependent multisite phosphorylation of AREB1 regulates its own activation in plants.

  2. Genome-wide targeted prediction of ABA responsive genes in rice based on over-represented cis-motif in co-expressed genes.

    PubMed

    Lenka, Sangram K; Lohia, Bikash; Kumar, Abhay; Chinnusamy, Viswanathan; Bansal, Kailash C

    2009-02-01

    Abscisic acid (ABA), the popular plant stress hormone, plays a key role in regulation of sub-set of stress responsive genes. These genes respond to ABA through specific transcription factors which bind to cis-regulatory elements present in their promoters. We discovered the ABA Responsive Element (ABRE) core (ACGT) containing CGMCACGTGB motif as over-represented motif among the promoters of ABA responsive co-expressed genes in rice. Targeted gene prediction strategy using this motif led to the identification of 402 protein coding genes potentially regulated by ABA-dependent molecular genetic network. RT-PCR analysis of arbitrarily chosen 45 genes from the predicted 402 genes confirmed 80% accuracy of our prediction. Plant Gene Ontology (GO) analysis of ABA responsive genes showed enrichment of signal transduction and stress related genes among diverse functional categories.

  3. Effect of thermal pre-treatment on inoculum sludge to enhance bio-hydrogen production from alkali hydrolysed rice straw in a mesophilic anaerobic baffled reactor.

    PubMed

    El-Bery, Haitham; Tawfik, Ahmed; Kumari, Sheena; Bux, Faizal

    2013-01-01

    The effect of thermal pre-treatment on inoculum sludge for continuous H2 production from alkali hydrolysed rice straw using anaerobic baffled reactor (ABR) was investigated. Two reactors, ABR1 and ABR2, were inoculated with untreated and thermally pre-treated sludge, respectively. Both reactors were operated in parallel at a constant hydraulic retention time of 20 h and organic loading rate ranged from 0.5 to 2.16 g COD/L d. The results obtained indicated that ABR2 achieved a better hydrogen conversion rate and hydrogen yield as compared with ABR1. The hydrogen conversion rates were 30% and 24%, while the hydrogen yields were 1.19 and 0.97 mol H2/mol glucose for ABR2 and ABR1, respectively. Similar trend was observed for chemical oxygen demand (COD) and carbohydrate removal, where ABR2 provided a removal efficiency of 53 +/- 2.3% for COD and 46 +/- 2% for carbohydrate. The microbial community analysis using 16S rRNA phylogeny revealed the presence of different species of bacteria, namely Clostridium, Prevotella, Paludibacter, Ensifer, and Petrimonas within the reactors. Volatile fatty acids generated from ABR1 and ABR2 were mainly in the form of acetate and butyrate and a relatively low fraction ofpropionate was detected in ABR1. Based on these results, thermal pre-treatment ofinoculum sludge is preferable for hydrogen production from hydrolysed rice straw.

  4. Auditory brainstem responses predict auditory nerve fiber thresholds and frequency selectivity in hearing impaired chinchillas

    PubMed Central

    Henry, Kenneth S.; Kale, Sushrut; Scheidt, Ryan E.; Heinz, Michael G.

    2011-01-01

    Non-invasive auditory brainstem responses (ABRs) are commonly used to assess cochlear pathology in both clinical and research environments. In the current study, we evaluated the relationship between ABR characteristics and more direct measures of cochlear function. We recorded ABRs and auditory nerve (AN) single-unit responses in seven chinchillas with noise induced hearing loss. ABRs were recorded for 1–8 kHz tone burst stimuli both before and several weeks after four hours of exposure to a 115 dB SPL, 50 Hz band of noise with a center frequency of 2 kHz. Shifts in ABR characteristics (threshold, wave I amplitude, and wave I latency) following hearing loss were compared to AN-fiber tuning curve properties (threshold and frequency selectivity) in the same animals. As expected, noise exposure generally resulted in an increase in ABR threshold and decrease in wave I amplitude at equal SPL. Wave I amplitude at equal sensation level (SL), however, was similar before and after noise exposure. In addition, noise exposure resulted in decreases in ABR wave I latency at equal SL and, to a lesser extent, at equal SPL. The shifts in ABR characteristics were significantly related to AN-fiber tuning curve properties in the same animal at the same frequency. Larger shifts in ABR thresholds and ABR wave I amplitude at equal SPL were associated with greater AN threshold elevation. Larger reductions in ABR wave I latency at equal SL, on the other hand, were associated with greater loss of AN frequency selectivity. This result is consistent with linear systems theory, which predicts shorter time delays for broader peripheral frequency tuning. Taken together with other studies, our results affirm that ABR thresholds and wave I amplitude provide useful estimates of cochlear sensitivity. Furthermore, comparisons of ABR wave I latency to normative data at the same SL may prove useful for detecting and characterizing loss of cochlear frequency selectivity. PMID:21699970

  5. [Effects of sevoflurane and propofol on evoked potentials during neurosurgical anesthesia].

    PubMed

    Nakagawa, Itsuo; Hidaka, Syozo; Okada, Hironori; Kubo, Takashi; Okamura, Kenta; Kato, Takahiro

    2006-06-01

    The effect of anesthetics on somatosensory evoked potential (SEP) and auditory brain stem response (ABR) has been a subject of intense reseach over the last two decades. In fact, volatile anesthetics have been repeatedly shown to decrease cortical amplitude in a dose-dependent fashion but the information regarding the effect of propofol is incomplete. The purpose of this study was to compare the effects of sevoflurane and propofol on evoked potentials during comparable depth of anesthesia guided by bispectral index (BIS). Forty four patients scheduled for neurosurgery were studied. Anesthesia was maintained with intravenous propofol using target controlled infusion (TCI). We measured the change of amplitude and latency of SEP(N20-P25), ABR (V wave) and visual evoked potential (VEP: P100) at three sets of sevoflurane (0%, 1%, 2%) or propofol concentrations (effect site concentration of 1.5, 2.0, 3.0 microug x ml(-1)). BIS monitor was used to measure relative depth of hypnosis. With increasing concentrations of sevoflurane (0, 1% and 2%), SEP showed dose-related reduction in its amplitude, ABR produced less marked changes and VEP showed a significant reduction at 1%. VEP at the propofol concentration of 3.0 microg x ml(-1) was decreased significantly compared with the amplitude at 1.5 microg x ml(-1) concentration. No significant change was observed with SEP and ABR during the change of propofol dosages. BIS values were almost the same with each anesthetics. VEP was most strongly affected with anesthetics, and ABR showed less marked influence of sevoflurane and propofol. Propofol based TIVA technique would induce less change in evoked potentials than sevoflurane.

  6. Maize DRE-binding proteins DBF1 and DBF2 are involved in rab17 regulation through the drought-responsive element in an ABA-dependent pathway.

    PubMed

    Kizis, Dimosthenis; Pagès, Montserrat

    2002-06-01

    The abscisic acid-responsive gene rab17 of maize is expressed during late embryogenesis, and is induced by ABA and desiccation in embryo and vegetative tissues. ABRE and DRE cis-elements are involved in regulation of the gene by ABA and drought. Using yeast one-hybrid screening, we isolated two cDNAs encoding two new DRE-binding proteins, designated DBF1 and DBF2, that are members of the AP2/EREBP transcription factor family. Analysis of mRNA accumulation profiles showed that DBF1 is induced during maize embryogenesis and after desiccation, NaCl and ABA treatments in plant seedlings, whereas the DBF2 mRNA is not induced. DNA-binding preferences of DBFs were analysed by electrophoretic mobility shift assays, and showed that both DBF1 and DBF2 bound to the wild-type DRE2 element, but not to the DRE2 mutant or to the DRE1 element which differs only in a single nucleotide. Transactivation activity using particle bombardment showed that DBF1 functioned as activator of DRE2-dependent transcription of rab17 promoter by ABA, whereas DBF2 overexpression had a repression action downregulating not only the basal promoter activity, but also the ABA effect. These results show that ABA plays a role in the regulation of DBF activity, and suggests the existence of an ABA-dependent pathway for the regulation of genes through the C-repeat/DRE element.

  7. Computational fluid dynamics (CFD) analysis of airlift bioreactor: effect of draft tube configurations on hydrodynamics, cell suspension, and shear rate.

    PubMed

    Pawar, Sanjay B

    2018-01-01

    The biomass productivity of microalgae cells mainly depends on the hydrodynamics of airlift bioreactor (ABR). Thus, the hydrodynamics of concentric tube ABR was initially studied using two-phase three-dimensional CFD simulations with the Eulerian-Lagrangian approach. The performance of ABR (17 L) was examined for different configurations of the draft tube using various drag models such as Grace, Ishii-Zuber, and Schiller-Naumann. The gas holdups in the riser and the downcomer were well predicted using E-L approach. This work was further extended to study the dispersion of microalgae cells in the ABR using three-phase CFD simulations. In this model (combined E-E and E-L), the solid phase (microalgae cells) was dispersed into the continuous liquid phase (water), while the gas phase (air bubbles) was modeled as a particle transport fluid. The effect of non-drag forces such as virtual mass and lift forces was also considered. Flow regimes were explained on the basis of the relative gas holdup distribution in the riser and the downcomer. The microalgae cells were found in suspension for the superficial gas velocities of 0.02-0.04 m s -1 experiencing an average shear of 23.52-44.56 s -1 which is far below the critical limit of cell damage.

  8. Attenuation of progressive hearing loss in DBA/2J mice by reagents that affect epigenetic modifications is associated with up-regulation of the zinc importer Zip4.

    PubMed

    Mutai, Hideki; Miya, Fuyuki; Fujii, Masato; Tsunoda, Tatsuhiko; Matsunaga, Tatsuo

    2015-01-01

    Various factors that are important for proper hearing have been identified, including serum levels of zinc. Here we investigated whether epigenetic regulatory pathways, which can be modified by environmental factors, could modulate hearing. RT-PCR detected expression of genes encoding DNA methyltransferase and histone deacetylase (Hdac) in the postnatal as well as adult mouse auditory epithelium. DBA/2J mice, which are a model for progressive hearing loss, were injected subcutaneously with one or a combination of the following reagents: L-methionine as a methyl donor, valproic acid as a pan-Hdac inhibitor, and folic acid and vitamin B12 as putative factors involved in age-related hearing loss. The mice were treated from ages 4 to 12 weeks (N ≥ 5), and auditory brainstem response (ABR) thresholds were measured at 8, 16, and 32 kHz. Treatment of the mice with a combination of L-methionine and valproic acid (M+V) significantly reduced the increase in the ABR threshold at 32 kHz. Treatment with any of these reagents individually produced no such effect. Microarray analyses detected 299 gene probes that were significantly up- or down-regulated in the cochleae of mice treated with M+V compared with the control vehicle-treated mice. Quantitative RT-PCR confirmed significant up-regulation of a zinc importer gene, Zip4, in the cochleae of mice treated with M+V. Immunohistochemistry demonstrated an intense Zip4 signal in cochlear tissues such as the lateral wall, organ of Corti, and spiral ganglion. Finally, mice treated with the Zip4 inducer (-)-epigallocatechin-3-O-gallate showed a significant reduction in the increase of the ABR threshold at 32 kHz and up-regulation of Zip4 expression in the cochlea. This study suggests that epigenetic regulatory pathways can modify auditory function and that zinc intake in the cochlea via Zip4 mediates maintenance of mammalian hearing.

  9. Newborn Auditory Brainstem Evoked Responses (ABRs): Longitudinal Correlates in the First Year.

    ERIC Educational Resources Information Center

    Murray, Ann D.

    1988-01-01

    Aimed to determine to what degree newborns' auditory brainstem evoked responses (ABRs) predict delayed or impaired development during the first year. When 93 infants' ABRs were evaluated at three, six, and nine months, newborn ABR was moderately sensitive for detecting hearing impairment and more sensitive than other indicators in detecting…

  10. Characterization of three multicopper oxidases in the filamentous fungus Podospora anserina: A new role of an ABR1-like protein in fungal development?

    PubMed

    Xie, Ning; Ruprich-Robert, Gwenaël; Silar, Philippe; Herbert, Eric; Ferrari, Roselyne; Chapeland-Leclerc, Florence

    2018-07-01

    The Podospora anserina genome contains a large family of 15 multicopper oxidases (MCOs), including three genes encoding a FET3-like protein, an ABR1-like protein and an ascorbate oxidase (AO)-like protein. FET3, ABR1 and AO1 are involved in global laccase-like activity since deletion of the relevant genes led to a decrease of activity when laccase substrate (ABTS) was used as substrate. However, contrary to the P. anserina MCO proteins previously characterized, none of these three MCOs seemed to be involved in lignocellulose degradation and in resistance to phenolic compounds and oxidative stress. We showed that the bulk of ferroxidase activity was clearly due to ABR1, and only in minor part to FET3, although ABR1 does not contain all the residues typical of FET3 proteins. Moreover, we showed that ABR1, related to the Aspergillus fumigatus ABR1 protein, was clearly and specifically involved in pigmentation of ascospores. Surprisingly, phenotypes were more severe in mutants lacking both abr1 and ao1. Deletion of the ao1 gene led to an almost total loss of AO activity. No direct involvement of AO1 in fungal developmental process in P. anserina was evidenced, except in a abr1 Δ background. Overall, unlike other previously characterized MCOs, we thus evidence a clear involvement of ABR1 protein in fungal development. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Auditory brainstem responses to broad-band chirps: amplitude growth functions in sedated and anaesthetised infants.

    PubMed

    Mühler, Roland; Rahne, Torsten; Verhey, Jesko L

    2013-01-01

    Recently an optimized broad-band chirp stimulus has been proposed for the objective estimation of hearing thresholds with auditory brainstem responses (ABRs). Several studies have demonstrated that this stimulus, compensating for the travelling wave delay of the frequency components of a click stimulus at the basilar membrane, evokes larger ABR amplitudes in adults. This study analyses the amplitude of chirp-evoked ABRs recorded in infants below 48 month of age under clinical conditions and compares these results with literature data. Chirp-evoked ABR recordings in 46 infants under chloral hydrate sedation or general anaesthesia were analysed retrospectively. The amplitude of the wave V was measured as a function of the stimulus intensity. To compare ABR amplitudes across infants with different hearing losses, the stimulus intensity was readjusted to the subjects' individual physiological threshold in dB SL (sensation level). Individual wave V amplitudes were plotted against stimulus intensity and individual amplitude growth functions were calculated. To investigate the maturation of chirp-evoked ABR, data from infants below and above 18 months of age were analysed separately. Chirp-evoked ABR amplitudes in both age groups were larger than the click-evoked ABR amplitudes in young infants from the literature. Amplitudes of chirp-evoked ABR in infants above 18 months of age were not substantially smaller than those reported for normal hearing adults. Amplitudes recorded in infants below 18 months were significantly smaller than those in infants above 18 months. A significant difference between chirp-evoked ABR amplitudes recorded in sedation or under general anaesthesia was not found. The higher amplitudes of ABR elicited by a broadband chirp stimulus allow for a reduction of the recording time in young infants. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. Individual Differences in Auditory Brainstem Response Wave Characteristics

    PubMed Central

    Jagadeesh, Anoop; Mauermann, Manfred; Ernst, Frauke

    2016-01-01

    Little is known about how outer hair cell loss interacts with noise-induced and age-related auditory nerve degradation (i.e., cochlear synaptopathy) to affect auditory brainstem response (ABR) wave characteristics. Given that listeners with impaired audiograms likely suffer from mixtures of these hearing deficits and that ABR amplitudes have successfully been used to isolate synaptopathy in listeners with normal audiograms, an improved understanding of how different hearing pathologies affect the ABR source generators will improve their sensitivity in hearing diagnostics. We employed a functional model for human ABRs in which different combinations of hearing deficits were simulated and show that high-frequency cochlear gain loss steepens the slope of the ABR Wave-V latency versus intensity and amplitude versus intensity curves. We propose that grouping listeners according to a ratio of these slope metrics (i.e., the ABR growth ratio) might offer a way to factor out the outer hair cell loss deficit and maximally relate individual differences for constant ratios to other peripheral hearing deficits such as cochlear synaptopathy. We compared the model predictions to recorded click-ABRs from 30 participants with normal or high-frequency sloping audiograms and confirm the predicted relationship between the ABR latency growth curve and audiogram slope. Experimental ABR amplitude growth showed large individual differences and was compared with the Wave-I amplitude, Wave-V/I ratio, or the interwaveI–W latency in the same listeners. The model simulations along with the ABR recordings suggest that a hearing loss profile depicting the ABR growth ratio versus the Wave-I amplitude or Wave-V/I ratio might be able to differentiate outer hair cell deficits from cochlear synaptopathy in listeners with mixed pathologies. PMID:27837052

  13. Identification of Cis-Acting Promoter Elements in Cold- and Dehydration-Induced Transcriptional Pathways in Arabidopsis, Rice, and Soybean

    PubMed Central

    Maruyama, Kyonoshin; Todaka, Daisuke; Mizoi, Junya; Yoshida, Takuya; Kidokoro, Satoshi; Matsukura, Satoko; Takasaki, Hironori; Sakurai, Tetsuya; Yamamoto, Yoshiharu Y.; Yoshiwara, Kyouko; Kojima, Mikiko; Sakakibara, Hitoshi; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2012-01-01

    The genomes of three plants, Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa), and soybean (Glycine max), have been sequenced, and their many genes and promoters have been predicted. In Arabidopsis, cis-acting promoter elements involved in cold- and dehydration-responsive gene expression have been extensively analysed; however, the characteristics of such cis-acting promoter sequences in cold- and dehydration-inducible genes of rice and soybean remain to be clarified. In this study, we performed microarray analyses using the three species, and compared characteristics of identified cold- and dehydration-inducible genes. Transcription profiles of the cold- and dehydration-responsive genes were similar among these three species, showing representative upregulated (dehydrin/LEA) and downregulated (photosynthesis-related) genes. All (46 = 4096) hexamer sequences in the promoters of the three species were investigated, revealing the frequency of conserved sequences in cold- and dehydration-inducible promoters. A core sequence of the abscisic acid-responsive element (ABRE) was the most conserved in dehydration-inducible promoters of all three species, suggesting that transcriptional regulation for dehydration-inducible genes is similar among these three species, with the ABRE-dependent transcriptional pathway. In contrast, for cold-inducible promoters, the conserved hexamer sequences were diversified among these three species, suggesting the existence of diverse transcriptional regulatory pathways for cold-inducible genes among the species. PMID:22184637

  14. The RY/Sph element mediates transcriptional repression of maturation genes from late maturation to early seedling growth.

    PubMed

    Guerriero, Gea; Martin, Nathalie; Golovko, Anna; Sundström, Jens F; Rask, Lars; Ezcurra, Ines

    2009-11-01

    In orthodox seeds, the transcriptional activator ABI3 regulates two major stages in embryo maturation: a mid-maturation (MAT) stage leading to accumulation of storage compounds, and a late maturation (LEA) stage leading to quiescence and desiccation tolerance. Our aim was to elucidate mechanisms for transcriptional shutdown of MAT genes during late maturation, to better understand phase transition between MAT and LEA stages. Using transgenic and transient approaches in Nicotiana, we examined activities of two ABI3-dependent reporter genes driven by multimeric RY and abscisic acid response elements (ABREs) from a Brassica napus napin gene, termed RY and ABRE, where the RY reporter requires ABI3 DNA binding. Expression of RY peaks during mid-maturation and drops during late maturation, mimicking the MAT gene program, and in Arabidopsis thaliana RY elements are over-represented in MAT, but not in LEA, genes. The ABI3 transactivation of RY is inhibited by staurosporine, by a PP2C phosphatase, and by a repressor of maturation genes, VAL1/HSI2. The RY element mediates repression of MAT genes, and we propose that transcriptional shutdown of the MAT program during late maturation involves inhibition of ABI3 DNA binding by dephosphorylation. Later, during seedling growth, VAL1/HSI2 family repressors silence MAT genes by binding RY elements.

  15. AhpA is a peroxidase expressed during biofilm formation in Bacillus subtilis.

    PubMed

    Zwick, Joelie V; Noble, Sarah; Ellaicy, Yasser K; Coe, Gabrielle Dierker; Hakey, Dylan J; King, Alyssa N; Sadauskas, Alex J; Faulkner, Melinda J

    2017-02-01

    Organisms growing aerobically generate reactive oxygen species such as hydrogen peroxide. These reactive oxygen molecules damage enzymes and DNA, potentially causing cell death. In response, Bacillus subtilis produces at least nine potential peroxide-scavenging enzymes; two belong to the alkylhydroperoxide reductase (Ahp) class of peroxidases. Here, we explore the role of one of these Ahp homologs, AhpA. While previous studies demonstrated that AhpA can scavenge peroxides and thus defend cells against peroxides, they did not clarify when during growth the cell produces AhpA. The results presented here show that the expression of ahpA is regulated in a manner distinct from that of the other peroxide-scavenging enzymes in B. subtilis. While the primary Ahp, AhpC, is expressed during exponential growth and stationary phase, these studies demonstrate that the expression of ahpA is dependent on the transition-state regulator AbrB and the sporulation and biofilm formation transcription factor Spo0A. Furthermore, these results show that ahpA is specifically expressed during biofilm formation, and not during sporulation or stationary phase, suggesting that derepression of ahpA by AbrB requires a signal other than those present upon entry into stationary phase. Despite this expression pattern, ahpA mutant strains still form and maintain robust biofilms, even in the presence of peroxides. Thus, the role of AhpA with regard to protecting cells within biofilms from environmental stresses is still uncertain. These studies highlight the need to further study the Ahp homologs to better understand how they differ from one another and the unique roles they may play in oxidative stress resistance. © 2016 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  16. Identification and characterization of cis-acting elements involved in the regulation of ABA- and/or GA-mediated LuPLR1 gene expression and lignan biosynthesis in flax (Linum usitatissimum L.) cell cultures.

    PubMed

    Corbin, Cyrielle; Renouard, Sullivan; Lopez, Tatiana; Lamblin, Frédéric; Lainé, Eric; Hano, Christophe

    2013-03-15

    Pinoresinol lariciresinol reductase 1, encoded by the LuPLR1 gene in flax (Linum usitatissimum L.), is responsible for the biosynthesis of (+)-secoisolariciresinol, a cancer chemopreventive phytoestrogenic lignan accumulated in high amount in the hull of flaxseed. Our recent studies have demonstrated a key role of abscisic acid (ABA) in the regulation of LuPLR1 gene expression and thus of the (+)-secoisolariciresinol synthesis during the flax seedcoat development. It is well accepted that gibberellins (GA) and ABA play antagonistic roles in the regulation of numerous developmental processes; therefore it is of interest to clarify their respective effects on lignan biosynthesis. Herein, using flax cell suspension cultures, we demonstrate that LuPLR1 gene expression and (+)-secoisolariciresinol synthesis are up-regulated by ABA and down-regulated by GA. The LuPLR1 gene promoter analysis and mutation experiments allow us to identify and characterize two important cis-acting sequences (ABRE and MYB2) required for these regulations. These results imply that a cross-talk between ABA and GA signaling orchestrated by transcription factors is involved in the regulation of lignan biosynthesis. This is particularly evidenced in the case of the ABRE cis-regulatory sequence of LuPLR1 gene promoter that appears to be a common target sequence of GA and ABA signals. Copyright © 2012 Elsevier GmbH. All rights reserved.

  17. [Comparison of tone burst evoked auditory brainstem responses with different filter settings for referral infants after hearing screening].

    PubMed

    Diao, Wen-wen; Ni, Dao-feng; Li, Feng-rong; Shang, Ying-ying

    2011-03-01

    Auditory brainstem responses (ABR) evoked by tone burst is an important method of hearing assessment in referral infants after hearing screening. The present study was to compare the thresholds of tone burst ABR with filter settings of 30 - 1500 Hz and 30 - 3000 Hz at each frequency, figure out the characteristics of ABR thresholds with the two filter settings and the effect of the waveform judgement, so as to select a more optimal frequency specific ABR test parameter. Thresholds with filter settings of 30 - 1500 Hz and 30 - 3000 Hz in children aged 2 - 33 months were recorded by click, tone burst ABR. A total of 18 patients (8 male/10 female), 22 ears were included. The thresholds of tone burst ABR with filter settings of 30 - 3000 Hz were higher than that with filter settings of 30 - 1500 Hz. Significant difference was detected for that at 0.5 kHz and 2.0 kHz (t values were 2.238 and 2.217, P < 0.05), no significant difference between the two filter settings was detected at the rest frequencies tone evoked ABR thresholds. The waveform of ABR with filter settings of 30 - 1500 Hz was smoother than that with filter settings of 30 - 3000 Hz at the same stimulus intensity. Response curve of the latter appeared jagged small interfering wave. The filter setting of 30 - 1500 Hz may be a more optimal parameter of frequency specific ABR to improve the accuracy of frequency specificity ABR for infants' hearing assessment.

  18. The utility of single-item readiness screeners in middle school.

    PubMed

    Lewis, Crystal G; Herman, Keith C; Huang, Francis L; Stormont, Melissa; Grossman, Caroline; Eddy, Colleen; Reinke, Wendy M

    2017-10-01

    This study examined the benefit of utilizing one-item academic and one-item behavior readiness teacher-rated screeners at the beginning of the school year to predict end-of-school year outcomes for middle school students. The Middle School Academic and Behavior Readiness (M-ABR) screeners were developed to provide an efficient and effective way to assess readiness in students. Participants included 889 students in 62 middle school classrooms in an urban Missouri school district. Concurrent validity with the M-ABR items and other indicators of readiness in the fall were evaluated using Pearson product-moment correlation coefficients, with the academic readiness item having medium to strong correlations with other baseline academic indicators (r=±0.56 to 0.91) and the behavior readiness item having low to strong correlations with baseline behavior items (r=±0.20 to 0.79). Next, the predictive validity of the M-ABR items was analyzed with hierarchical linear regressions using end-of-year outcomes as the dependent variable. The academic and behavior readiness items demonstrated adequate validity for all outcomes with moderate effects (β=±0.31 to 0.73 for academic outcomes and β=±0.24 to 0.59 for behavioral outcomes) after controlling for baseline demographics. Even after controlling for baseline scores, the M-ABR items predicted unique variance in almost all outcome variables. Four conditional probability indices were calculated to obtain an optimal cut score, to determine ready vs. not ready, for both single-item M-ABR scales. The cut point of "fair" yielded the most acceptable values for the indices. The odd ratios (OR) of experiencing negative outcomes given a "fair" or lower readiness rating (2 or below on the M-ABR screeners) at the beginning of the year were significant and strong for all outcomes (OR=2.29 to OR=14.46), except for internalizing problems. These findings suggest promise for using single readiness items to screen for varying negative end-of-year student outcomes. Copyright © 2017 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

  19. Repeated antenatal corticosteroid treatments adversely affect neural transmission time and auditory thresholds in laboratory rats.

    PubMed

    Church, M W; Adams, B R; Anumba, J I; Jackson, D A; Kruger, M L; Jen, K-L C

    2012-01-01

    Antenatal corticosteroid (AC) treatment is given to pregnant women at risk for preterm birth to reduce infant morbidity and mortality by enhancing lung and brain maturation. However, there is no accepted regimen on how frequently AC treatments should be given and some studies found that repeated AC treatments can cause growth retardation and brain damage. Our goal was to assess the dose-dependent effects of repeated AC treatment and estimate the critical number of AC courses to cause harmful effects on the auditory brainstem response (ABR), a sensitive measure of brain development, neural transmission and hearing loss. We hypothesized that repeated AC treatment would have harmful effects on the offspring's ABRs and growth only if more than 3 AC treatment courses were given. To test this hypothesis, pregnant Wistar rats were given either a high regimen of AC (HAC), a moderate regimen (MAC), a low regimen (LAC), or saline (SAL). An untreated control (CON) group was also used. Simulating the clinical condition, the HAC dams received 0.2mg/kg Betamethasone (IM) twice daily for 6 days during gestation days (GD) 17-22. The MAC dams received 3 days of AC treatment followed by 3 days of saline treatment on GD 17-19 and GD 20-22, respectively. The LAC dams received 1 day of AC treatment followed by 5 days of saline treatment on GD 17 and GD 18-22, respectively. The SAL dams received 6 days of saline treatment from GD 17 to 22 (twice daily, isovolumetric to the HAC injections, IM). The offspring were ABR-tested on postnatal day 24. Results indicated that the ABR's P4 latencies (neural transmission time) were significantly prolonged (worse) in the HAC pups and that ABR's thresholds were significantly elevated (worse) in the HAC and MAC pups when compared to the CON pups. The HAC and MAC pups were also growth retarded and had higher postnatal mortality than the CON pups. The SAL and LAC pups showed little or no adverse effects. In conclusion, repeated AC treatment had harmful effects on the rat offspring's ABRs, postnatal growth and survival. The prolonged ABR latencies reflect slowed neural transmission times along the auditory nerve and brainstem auditory pathway. The elevated ABR thresholds reflect hearing deficits. We concluded that repeated AC treatment can have harmful neurological, sensory and developmental effects on the rat offspring. These effects should be considered when weighing the benefits and risks of repeated AC treatment and when monitoring and managing the prenatally exposed child for possible adverse effects. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Auditory brainstem responses in the Eastern Screech Owl: An estimate of auditory thresholds

    USGS Publications Warehouse

    Brittan-Powell, E.F.; Lohr, B.; Hahn, D.C.; Dooling, R.J.

    2005-01-01

    The auditory brainstem response (ABR), a measure of neural synchrony, was used to estimate auditory sensitivity in the eastern screech owl (Megascops asio). The typical screech owl ABR waveform showed two to three prominent peaks occurring within 5 ms of stimulus onset. As sound pressure levels increased, the ABR peak amplitude increased and latency decreased. With an increasing stimulus presentation rate, ABR peak amplitude decreased and latency increased. Generally, changes in the ABR waveform to stimulus intensity and repetition rate are consistent with the pattern found in several avian families. The ABR audiogram shows that screech owls hear best between 1.5 and 6.4 kHz with the most acute sensitivity between 4?5.7 kHz. The shape of the average screech owl ABR audiogram is similar to the shape of the behaviorally measured audiogram of the barn owl, except at the highest frequencies. Our data also show differences in overall auditory sensitivity between the color morphs of screech owls.

  1. Gender Disparities in Speech-evoked Auditory Brainstem Response in Healthy Adults.

    PubMed

    Jalaei, Bahram; Zakaria, Mohd Normani; Mohd Azmi, Mohd Hafiz Afifi; Nik Othman, Nik Adilah; Sidek, Dinsuhaimi

    2017-04-01

    Gender disparities in speech-evoked auditory brainstem response (speech-ABR) outcomes have been reported, but the literature is limited. The present study was performed to further verify this issue and determine the influence of head size on speech-ABR results between genders. Twenty-nine healthy Malaysian subjects (14 males and 15 females) aged 19 to 30 years participated in this study. After measuring the head circumference, speech-ABR was recorded by using synthesized syllable /da/ from the right ear of each participant. Speech-ABR peaks amplitudes, peaks latencies, and composite onset measures were computed and analyzed. Significant gender disparities were noted in the transient component but not in the sustained component of speech-ABR. Statistically higher V/A amplitudes and less steeper V/A slopes were found in females. These gender differences were partially affected after controlling for the head size. Head size is not the main contributing factor for gender disparities in speech-ABR outcomes. Gender-specific normative data can be useful when recording speech-ABR for clinical purposes.

  2. Management update of acute bacterial rhinosinusitis and the use of cefdinir.

    PubMed

    Gwaltney, Jack M

    2002-12-01

    The pathogenesis, bacteriology, diagnosis, and antimicrobial treatment of acute bacterial rhinosinusitis (ABRS) is reviewed. Most cases of ABRS arise as complications of the rhinosinusitis of colds and other acute viral respiratory infections. Nose blowing during colds may be a risk factor for ABRS by propelling bacteria-laden nasal fluid into the sinus cavity. The bacterial causes of ABRS continue to be S pneumoniae. H influenzae, other streptococcal species, M catarrhalis, anaerobes, and S aureus. Clinical diagnosis of ABRS is based on obtaining a history of a cold or influenza-like illness that is no better or worse after >/=7 days. A 10-day course of treatment with an antimicrobial effective against resistant S pneumoniae and H influenzae is recommended. A clinical trial was reviewed in which cefdinir was effective in treating ABRS.

  3. Chloral hydrate sedation for auditory brainstem response (ABR) testing in children: Safety and effectiveness.

    PubMed

    Valenzuela, Dianne G; Kumar, Divjot Singh; Atkins, Cheryl Labelle; Beers, Alison; Kozak, Frederick K; Chadha, Neil K

    2016-04-01

    The auditory brainstem response (ABR) test is used to identify hearing loss and measure hearing thresholds of infants and children who cannot be tested using standard behavioral hearing testing methods. In order for the ABR to yield useful data, a child must be asleep throughout the duration of the test. In many centers, this is achieved through the use of a general anesthetic, with its inherent risks and costs. Since 2004, ABRs have been routinely conducted at BC Children's Hospital in an ambulatory care setting under oral chloral hydrate sedation, with monitoring by a specialist nurse. The aim of this retrospective study was to assess the effectiveness and safety of nurse-led sedation with chloral hydrate for ABR testing at our tertiary pediatric center. Medical and audiology records were reviewed for children aged 6 months to 17 years who underwent ABR testing from 2004 to 2012. We reviewed the dosage of drug used, condition of the child after chloral hydrate administration, adverse effects, audiological results, patients' vital signs, and the effectiveness of the sedative in keeping the child asleep throughout the duration of the test. Frequency distributions were derived for adverse outcomes. 725 ABR records encompassing 635 children (multiple ABR tests in some children) were reviewed. The average dose of chloral hydrate used was 52mg/kg. The majority of sedated ABR's (80.8%) were completed without any incident. Significant events [apnea and/or bradycardia], minor complications [vomiting, hypoxemia, prolonged sedation, and/or tachypnea] and restlessness were noted in 3.4%, 6.2%, and 5.0% of the cases, respectively. The majority of these issues resolved without medical intervention, such as the need to provide supplementary oxygen. In 95.9% of ABRs, chloral hydrate was successful in sedating the child adequately to answer the audiological question. This forms the largest study to date on oral sedation for ABR testing. Based on our results, the use of chloral hydrate in the presence of a sedation nurse was a safe and reliable method of performing ABR in infants and children. This may be of significant value to centres worldwide exploring alternatives to general anesthesia for ABR testing. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. MO-F-204-00: Preparing for the ABR Diagnostic and Nuclear Medical Physics Exams

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

    NONE

    Adequate, efficient preparation for the ABR Diagnostic and Nuclear Medical Physics exams is key to successfully obtain ABR certification. Each part of the ABR exam presents its own challenges: Part I: Determine the scope of basic medical physics study material, efficiently review this material, and solve related written questions/problems. Part II: Understand imaging principles, modalities, and systems, including image acquisition, processing, and display. Understand the relationship between imaging techniques, image quality, patient dose and safety, and solve related written questions/problems. Part III: Gain crucial, practical, clinical medical physics experience. Effectively communicate and explain the practice, performance, and significance of allmore » aspects of clinical medical physics. All parts of the ABR exam require specific skill sets and preparation: mastery of basic physics and imaging principles; written problem solving often involving rapid calculation; responding clearly and succinctly to oral questions about the practice, methods, and significance of clinical medical physics. This symposium focuses on the preparation necessary for each part of the ABR exam. Although there is some overlap, the nuclear exam covers a different body of knowledge than the diagnostic exam. A separate speaker will address those unique aspects of the nuclear exam, and how preparing for a second specialty differs from the first. Medical physicists who recently completed each ABR exam portion will share their experiences, insights, and preparation methods to help attendees best prepare for the challenges of each part of the ABR exam. In accordance with ABR exam security policy, no recalls or exam questions will be discussed. Learning Objectives: How to prepare for Part 1 of the ABR exam by determining the scope of basic medical physics study material and related problem solving/calculations How to prepare for Part 2 of the ABR exam by understanding diagnostic and/or nuclear imaging physics, systems, dosimetry, safety and related problem solving/calculations How to prepare for Part 3 of the ABR exam by effectively communicating the practice, methods, and significance of clinical diagnostic and/or nuclear medical physics.« less

  5. MO-F-204-02: Preparing for Part 2 of the ABR Diagnostic Physics Exam

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

    Szczykutowicz, T.

    Adequate, efficient preparation for the ABR Diagnostic and Nuclear Medical Physics exams is key to successfully obtain ABR certification. Each part of the ABR exam presents its own challenges: Part I: Determine the scope of basic medical physics study material, efficiently review this material, and solve related written questions/problems. Part II: Understand imaging principles, modalities, and systems, including image acquisition, processing, and display. Understand the relationship between imaging techniques, image quality, patient dose and safety, and solve related written questions/problems. Part III: Gain crucial, practical, clinical medical physics experience. Effectively communicate and explain the practice, performance, and significance of allmore » aspects of clinical medical physics. All parts of the ABR exam require specific skill sets and preparation: mastery of basic physics and imaging principles; written problem solving often involving rapid calculation; responding clearly and succinctly to oral questions about the practice, methods, and significance of clinical medical physics. This symposium focuses on the preparation necessary for each part of the ABR exam. Although there is some overlap, the nuclear exam covers a different body of knowledge than the diagnostic exam. A separate speaker will address those unique aspects of the nuclear exam, and how preparing for a second specialty differs from the first. Medical physicists who recently completed each ABR exam portion will share their experiences, insights, and preparation methods to help attendees best prepare for the challenges of each part of the ABR exam. In accordance with ABR exam security policy, no recalls or exam questions will be discussed. Learning Objectives: How to prepare for Part 1 of the ABR exam by determining the scope of basic medical physics study material and related problem solving/calculations How to prepare for Part 2 of the ABR exam by understanding diagnostic and/or nuclear imaging physics, systems, dosimetry, safety and related problem solving/calculations How to prepare for Part 3 of the ABR exam by effectively communicating the practice, methods, and significance of clinical diagnostic and/or nuclear medical physics.« less

  6. MO-F-204-03: Preparing for Part 3 of the ABR Diagnostic Physics Exam

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

    Zambelli, J.

    Adequate, efficient preparation for the ABR Diagnostic and Nuclear Medical Physics exams is key to successfully obtain ABR certification. Each part of the ABR exam presents its own challenges: Part I: Determine the scope of basic medical physics study material, efficiently review this material, and solve related written questions/problems. Part II: Understand imaging principles, modalities, and systems, including image acquisition, processing, and display. Understand the relationship between imaging techniques, image quality, patient dose and safety, and solve related written questions/problems. Part III: Gain crucial, practical, clinical medical physics experience. Effectively communicate and explain the practice, performance, and significance of allmore » aspects of clinical medical physics. All parts of the ABR exam require specific skill sets and preparation: mastery of basic physics and imaging principles; written problem solving often involving rapid calculation; responding clearly and succinctly to oral questions about the practice, methods, and significance of clinical medical physics. This symposium focuses on the preparation necessary for each part of the ABR exam. Although there is some overlap, the nuclear exam covers a different body of knowledge than the diagnostic exam. A separate speaker will address those unique aspects of the nuclear exam, and how preparing for a second specialty differs from the first. Medical physicists who recently completed each ABR exam portion will share their experiences, insights, and preparation methods to help attendees best prepare for the challenges of each part of the ABR exam. In accordance with ABR exam security policy, no recalls or exam questions will be discussed. Learning Objectives: How to prepare for Part 1 of the ABR exam by determining the scope of basic medical physics study material and related problem solving/calculations How to prepare for Part 2 of the ABR exam by understanding diagnostic and/or nuclear imaging physics, systems, dosimetry, safety and related problem solving/calculations How to prepare for Part 3 of the ABR exam by effectively communicating the practice, methods, and significance of clinical diagnostic and/or nuclear medical physics.« less

  7. MO-F-204-01: Preparing for Part 1 of the ABR Diagnostic Physics Exam

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

    McKenney, S.

    Adequate, efficient preparation for the ABR Diagnostic and Nuclear Medical Physics exams is key to successfully obtain ABR certification. Each part of the ABR exam presents its own challenges: Part I: Determine the scope of basic medical physics study material, efficiently review this material, and solve related written questions/problems. Part II: Understand imaging principles, modalities, and systems, including image acquisition, processing, and display. Understand the relationship between imaging techniques, image quality, patient dose and safety, and solve related written questions/problems. Part III: Gain crucial, practical, clinical medical physics experience. Effectively communicate and explain the practice, performance, and significance of allmore » aspects of clinical medical physics. All parts of the ABR exam require specific skill sets and preparation: mastery of basic physics and imaging principles; written problem solving often involving rapid calculation; responding clearly and succinctly to oral questions about the practice, methods, and significance of clinical medical physics. This symposium focuses on the preparation necessary for each part of the ABR exam. Although there is some overlap, the nuclear exam covers a different body of knowledge than the diagnostic exam. A separate speaker will address those unique aspects of the nuclear exam, and how preparing for a second specialty differs from the first. Medical physicists who recently completed each ABR exam portion will share their experiences, insights, and preparation methods to help attendees best prepare for the challenges of each part of the ABR exam. In accordance with ABR exam security policy, no recalls or exam questions will be discussed. Learning Objectives: How to prepare for Part 1 of the ABR exam by determining the scope of basic medical physics study material and related problem solving/calculations How to prepare for Part 2 of the ABR exam by understanding diagnostic and/or nuclear imaging physics, systems, dosimetry, safety and related problem solving/calculations How to prepare for Part 3 of the ABR exam by effectively communicating the practice, methods, and significance of clinical diagnostic and/or nuclear medical physics.« less

  8. MO-F-204-04: Preparing for Parts 2 & 3 of the ABR Nuclear Medicine Physics Exam

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

    MacDougall, R.

    Adequate, efficient preparation for the ABR Diagnostic and Nuclear Medical Physics exams is key to successfully obtain ABR certification. Each part of the ABR exam presents its own challenges: Part I: Determine the scope of basic medical physics study material, efficiently review this material, and solve related written questions/problems. Part II: Understand imaging principles, modalities, and systems, including image acquisition, processing, and display. Understand the relationship between imaging techniques, image quality, patient dose and safety, and solve related written questions/problems. Part III: Gain crucial, practical, clinical medical physics experience. Effectively communicate and explain the practice, performance, and significance of allmore » aspects of clinical medical physics. All parts of the ABR exam require specific skill sets and preparation: mastery of basic physics and imaging principles; written problem solving often involving rapid calculation; responding clearly and succinctly to oral questions about the practice, methods, and significance of clinical medical physics. This symposium focuses on the preparation necessary for each part of the ABR exam. Although there is some overlap, the nuclear exam covers a different body of knowledge than the diagnostic exam. A separate speaker will address those unique aspects of the nuclear exam, and how preparing for a second specialty differs from the first. Medical physicists who recently completed each ABR exam portion will share their experiences, insights, and preparation methods to help attendees best prepare for the challenges of each part of the ABR exam. In accordance with ABR exam security policy, no recalls or exam questions will be discussed. Learning Objectives: How to prepare for Part 1 of the ABR exam by determining the scope of basic medical physics study material and related problem solving/calculations How to prepare for Part 2 of the ABR exam by understanding diagnostic and/or nuclear imaging physics, systems, dosimetry, safety and related problem solving/calculations How to prepare for Part 3 of the ABR exam by effectively communicating the practice, methods, and significance of clinical diagnostic and/or nuclear medical physics.« less

  9. WE-D-213-04: Preparing for Parts 2 & 3 of the ABR Nuclear Medicine Physics Exam

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

    MacDougall, R.

    Adequate, efficient preparation for the ABR Diagnostic and Nuclear Medical Physics exams is key to successfully obtain ABR professional certification. Each part of the ABR exam presents its own challenges: Part I: Determine the scope of basic medical physics study material, efficiently review this material, and solve related written questions/problems. Part II: Understand imaging principles, modalities, and systems, including image acquisition, processing, and display. Understand the relationship between imaging techniques, image quality, patient dose and safety, and solve related written questions/problems. Part III: Gain crucial, practical, clinical medical physics experience. Effectively communicate and explain the practice, performance, and significance ofmore » all aspects of clinical medical physics. All three parts of the ABR exam require specific skill sets and preparation: mastery of basic physics and imaging principles; written problem solving often involving rapid calculation; responding clearly and succinctly to oral questions about the practice, methods, and significance of clinical medical physics. This symposium focuses on the preparation and skill sets necessary for each part of the ABR exam. Although there is some overlap, the nuclear exam covers a different body of knowledge than the diagnostic exam. A separate speaker will address those aspects that are unique to the nuclear exam. Medical physicists who have recently completed each of part of the ABR exam will share their experiences, insights, and preparation methods to help attendees best prepare for the challenges of each part of the ABR exam. In accordance with ABR exam security policy, no recalls or exam questions will be discussed. Learning Objectives: How to prepare for Part 1 of the ABR exam by determining the scope of basic medical physics study material and related problem solving/calculations How to Prepare for Part 2 of the ABR exam by understanding diagnostic and/or nuclear imaging physics, systems, dosimetry, safety and related problem solving/calculations How to Prepare for Part 3 of the ABR exam by effectively communicating the practice, methods, and significance of clinical diagnostic and/or nuclear medical physics.« less

  10. WE-D-213-00: Preparing for the ABR Diagnostic and Nuclear Medicine Physics Exams

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

    NONE

    Adequate, efficient preparation for the ABR Diagnostic and Nuclear Medical Physics exams is key to successfully obtain ABR professional certification. Each part of the ABR exam presents its own challenges: Part I: Determine the scope of basic medical physics study material, efficiently review this material, and solve related written questions/problems. Part II: Understand imaging principles, modalities, and systems, including image acquisition, processing, and display. Understand the relationship between imaging techniques, image quality, patient dose and safety, and solve related written questions/problems. Part III: Gain crucial, practical, clinical medical physics experience. Effectively communicate and explain the practice, performance, and significance ofmore » all aspects of clinical medical physics. All three parts of the ABR exam require specific skill sets and preparation: mastery of basic physics and imaging principles; written problem solving often involving rapid calculation; responding clearly and succinctly to oral questions about the practice, methods, and significance of clinical medical physics. This symposium focuses on the preparation and skill sets necessary for each part of the ABR exam. Although there is some overlap, the nuclear exam covers a different body of knowledge than the diagnostic exam. A separate speaker will address those aspects that are unique to the nuclear exam. Medical physicists who have recently completed each of part of the ABR exam will share their experiences, insights, and preparation methods to help attendees best prepare for the challenges of each part of the ABR exam. In accordance with ABR exam security policy, no recalls or exam questions will be discussed. Learning Objectives: How to prepare for Part 1 of the ABR exam by determining the scope of basic medical physics study material and related problem solving/calculations How to Prepare for Part 2 of the ABR exam by understanding diagnostic and/or nuclear imaging physics, systems, dosimetry, safety and related problem solving/calculations How to Prepare for Part 3 of the ABR exam by effectively communicating the practice, methods, and significance of clinical diagnostic and/or nuclear medical physics.« less

  11. WE-D-213-01: Preparing for Part 1 of the ABR Diagnostic Physics Exam

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

    Simiele, S.

    Adequate, efficient preparation for the ABR Diagnostic and Nuclear Medical Physics exams is key to successfully obtain ABR professional certification. Each part of the ABR exam presents its own challenges: Part I: Determine the scope of basic medical physics study material, efficiently review this material, and solve related written questions/problems. Part II: Understand imaging principles, modalities, and systems, including image acquisition, processing, and display. Understand the relationship between imaging techniques, image quality, patient dose and safety, and solve related written questions/problems. Part III: Gain crucial, practical, clinical medical physics experience. Effectively communicate and explain the practice, performance, and significance ofmore » all aspects of clinical medical physics. All three parts of the ABR exam require specific skill sets and preparation: mastery of basic physics and imaging principles; written problem solving often involving rapid calculation; responding clearly and succinctly to oral questions about the practice, methods, and significance of clinical medical physics. This symposium focuses on the preparation and skill sets necessary for each part of the ABR exam. Although there is some overlap, the nuclear exam covers a different body of knowledge than the diagnostic exam. A separate speaker will address those aspects that are unique to the nuclear exam. Medical physicists who have recently completed each of part of the ABR exam will share their experiences, insights, and preparation methods to help attendees best prepare for the challenges of each part of the ABR exam. In accordance with ABR exam security policy, no recalls or exam questions will be discussed. Learning Objectives: How to prepare for Part 1 of the ABR exam by determining the scope of basic medical physics study material and related problem solving/calculations How to Prepare for Part 2 of the ABR exam by understanding diagnostic and/or nuclear imaging physics, systems, dosimetry, safety and related problem solving/calculations How to Prepare for Part 3 of the ABR exam by effectively communicating the practice, methods, and significance of clinical diagnostic and/or nuclear medical physics.« less

  12. WE-D-213-03: Preparing for Part 3 of the ABR Diagnostic Physics Exam

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

    Bevins, N.

    Adequate, efficient preparation for the ABR Diagnostic and Nuclear Medical Physics exams is key to successfully obtain ABR professional certification. Each part of the ABR exam presents its own challenges: Part I: Determine the scope of basic medical physics study material, efficiently review this material, and solve related written questions/problems. Part II: Understand imaging principles, modalities, and systems, including image acquisition, processing, and display. Understand the relationship between imaging techniques, image quality, patient dose and safety, and solve related written questions/problems. Part III: Gain crucial, practical, clinical medical physics experience. Effectively communicate and explain the practice, performance, and significance ofmore » all aspects of clinical medical physics. All three parts of the ABR exam require specific skill sets and preparation: mastery of basic physics and imaging principles; written problem solving often involving rapid calculation; responding clearly and succinctly to oral questions about the practice, methods, and significance of clinical medical physics. This symposium focuses on the preparation and skill sets necessary for each part of the ABR exam. Although there is some overlap, the nuclear exam covers a different body of knowledge than the diagnostic exam. A separate speaker will address those aspects that are unique to the nuclear exam. Medical physicists who have recently completed each of part of the ABR exam will share their experiences, insights, and preparation methods to help attendees best prepare for the challenges of each part of the ABR exam. In accordance with ABR exam security policy, no recalls or exam questions will be discussed. Learning Objectives: How to prepare for Part 1 of the ABR exam by determining the scope of basic medical physics study material and related problem solving/calculations How to Prepare for Part 2 of the ABR exam by understanding diagnostic and/or nuclear imaging physics, systems, dosimetry, safety and related problem solving/calculations How to Prepare for Part 3 of the ABR exam by effectively communicating the practice, methods, and significance of clinical diagnostic and/or nuclear medical physics.« less

  13. WE-D-213-02: Preparing for Part 2 of the ABR Diagnostic Physics Exam

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

    Zambelli, J.

    Adequate, efficient preparation for the ABR Diagnostic and Nuclear Medical Physics exams is key to successfully obtain ABR professional certification. Each part of the ABR exam presents its own challenges: Part I: Determine the scope of basic medical physics study material, efficiently review this material, and solve related written questions/problems. Part II: Understand imaging principles, modalities, and systems, including image acquisition, processing, and display. Understand the relationship between imaging techniques, image quality, patient dose and safety, and solve related written questions/problems. Part III: Gain crucial, practical, clinical medical physics experience. Effectively communicate and explain the practice, performance, and significance ofmore » all aspects of clinical medical physics. All three parts of the ABR exam require specific skill sets and preparation: mastery of basic physics and imaging principles; written problem solving often involving rapid calculation; responding clearly and succinctly to oral questions about the practice, methods, and significance of clinical medical physics. This symposium focuses on the preparation and skill sets necessary for each part of the ABR exam. Although there is some overlap, the nuclear exam covers a different body of knowledge than the diagnostic exam. A separate speaker will address those aspects that are unique to the nuclear exam. Medical physicists who have recently completed each of part of the ABR exam will share their experiences, insights, and preparation methods to help attendees best prepare for the challenges of each part of the ABR exam. In accordance with ABR exam security policy, no recalls or exam questions will be discussed. Learning Objectives: How to prepare for Part 1 of the ABR exam by determining the scope of basic medical physics study material and related problem solving/calculations How to Prepare for Part 2 of the ABR exam by understanding diagnostic and/or nuclear imaging physics, systems, dosimetry, safety and related problem solving/calculations How to Prepare for Part 3 of the ABR exam by effectively communicating the practice, methods, and significance of clinical diagnostic and/or nuclear medical physics.« less

  14. Regulatory elements in vivo in the promoter of the abscisic acid responsive gene rab17 from maize.

    PubMed

    Busk, P K; Jensen, A B; Pagès, M

    1997-06-01

    The rab17 gene from maize is transcribed in late embryonic development and is responsive to abscisic acid and water stress in embryo and vegetative tissues. In vivo footprinting and transient transformation of rab17 were performed in embryos and vegetative tissues to characterize the cis-elements involved in regulation of the gene. By in vivo footprinting, protein binding was observed to nine elements in the promoter, which correspond to five putative ABREs (abscisic acid responsive elements) and four other sequences. The footprints indicated that distinct proteins interact with these elements in the two developmental stages. In transient transformation, six of the elements were important for high level expression of the rab17 promoter in embryos, whereas only three elements were important in leaves. The cis-acting sequences can be divided in embryo-specific, ABA-specific and leaf-specific elements on the basis of protein binding and the ability to confer expression of rab17. We found one positive, new element, called GRA, with the sequence CACTGGCCGCCC. This element was important for transcription in leaves but not in embryos. Two other non-ABRE elements that stimulated transcription from the rab17 promoter resemble previously described abscisic acid and drought-inducible elements. There were differences in protein binding and function of the five ABREs in the rab17 promoter. The possible reasons for these differences are discussed. The in vivo data obtained suggest that an embryo-specific pathway regulates transcription of the rab genes during development, whereas another pathway is responsible for induction in response to ABA and drought in vegetative tissues.

  15. Notched-noise embedded frequency specific chirps for objective audiometry using auditory brainstem responses

    PubMed Central

    Corona-Strauss, Farah I.; Schick, Bernhard; Delb, Wolfgang; Strauss, Daniel J.

    2012-01-01

    It has been shown recently that chirp-evoked auditory brainstem responses (ABRs) show better performance than click stimulations, especially at low intensity levels. In this paper we present the development, test, and evaluation of a series of notched-noise embedded frequency specific chirps. ABRs were collected in healthy young control subjects using the developed stimuli. Results of the analysis of the corresponding ABRs using a time-scale phase synchronization stability (PSS) measure are also reported. The resultant wave V amplitude and latency measures showed a similar behavior as for values reported in literature. The PSS of frequency specific chirp-evoked ABRs reflected the presence of the wave V for all stimulation intensities. The scales that resulted in higher PSS are in line with previous findings, where ABRs evoked by broadband chirps were analyzed, and which stated that low frequency channels are better for the recognition and analysis of chirp-evoked ABRs. We conclude that the development and test of the series of notched-noise embedded frequency specific chirps allowed the assessment of frequency specific ABRs, showing an identifiable wave V for different intensity levels. Future work may include the development of a faster automatic recognition scheme for these frequency specific ABRs. PMID:26557336

  16. Stability and sensitivity of ABR flow control protocols

    NASA Astrophysics Data System (ADS)

    Tsai, Wie K.; Kim, Yuseok; Chiussi, Fabio; Toh, Chai-Keong

    1998-10-01

    This tutorial paper surveys the important issues in stability and sensitivity analysis of ABR flow control of ATM networks. THe stability and sensitivity issues are formulated in a systematic framework. Four main cause of instability in ABR flow control are identified: unstable control laws, temporal variations of available bandwidth with delayed feedback control, misbehaving components, and interactions between higher layer protocols and ABR flow control. Popular rate-based ABR flow control protocols are evaluated. Stability and sensitivity is shown to be the fundamental issues when the network has dynamically-varying bandwidth. Simulation result confirming the theoretical studies are provided. Open research problems are discussed.

  17. Neurophysiologic measures of auditory function in fish consumers: associations with long chain polyunsaturated fatty acids and methylmercury.

    PubMed

    Dziorny, Adam C; Orlando, Mark S; Strain, J J; Davidson, Philip W; Myers, Gary J

    2013-09-01

    Determining if associations exist between child neurodevelopment and environmental exposures, especially low level or background ones, is challenging and dependent upon being able to measure specific and sensitive endpoints. Psychometric or behavioral measures of CNS function have traditionally been used in such studies, but do have some limitations. Auditory neurophysiologic measures examine different nervous system structures and mechanisms, have fewer limitations, can more easily be quantified, and might be helpful additions to testing. To date, their use in human epidemiological studies has been limited. We reviewed the use of auditory brainstem responses (ABR) and otoacoustic emissions (OAE) in studies designed to determine the relationship of exposures to methyl mercury (MeHg) and nutrients from fish consumption with neurological development. We included studies of experimental animals and humans in an effort to better understand the possible benefits and risks of fish consumption. We reviewed the literature on the use of ABR and OAE to measure associations with environmental exposures that result from consuming a diet high in fish. We focused specifically on long chain polyunsaturated fatty acids (LCPUFA) and MeHg. We performed a comprehensive review of relevant studies using web-based search tools and appropriate search terms. Gestational exposure to both LCPUFA and MeHg has been reported to influence the developing auditory system. In experimental studies supplemental LCPUFA is reported to prolong ABR latencies and human studies also suggest an association. Experimental studies of acute and gestational MeHg exposure are reported to prolong ABR latencies and impair hair cell function. In humans, MeHg exposure is reported to prolong ABR latencies, but the impact on hair cell function is unknown. The auditory system can provide objective measures and may be useful in studying exposures to nutrients and toxicants and whether they are associated with children's neurodevelopment. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Soil Carbon Residence Time in the Arctic - Potential Drivers of Past and Future Change

    NASA Astrophysics Data System (ADS)

    Huntzinger, D. N.; Fisher, J.; Schwalm, C. R.; Hayes, D. J.; Stofferahn, E.; Hantson, W.; Schaefer, K. M.; Fang, Y.; Michalak, A. M.; Wei, Y.

    2017-12-01

    Carbon residence time is one of the most important factors controlling carbon cycling in ecosystems. Residence time depends on carbon allocation and conversion among various carbon pools and the rate of organic matter decomposition; all of which rely on environmental conditions, primarily temperature and soil moisture. As a result, residence time is an emergent property of models and a strong determinant of terrestrial carbon storage capacity. However, residence time is poorly constrained in process-based models due, in part, to the lack of data with which to benchmark global-scale models in order to guide model improvements and, ultimately, reduce uncertainty in model projections. Here we focus on improving the understanding of the drivers to observed and simulated carbon residence time in the Arctic-Boreal region (ABR). Carbon-cycling in the ABR represents one of the largest sources of uncertainty in historical and future projections of land-atmosphere carbon dynamics. This uncertainty is depicted in the large spread of terrestrial biospheric model (TBM) estimates of carbon flux and ecosystem carbon pool size in this region. Recent efforts, such as the Arctic-Boreal Vulnerability Experiment (ABoVE), have increased the availability of spatially explicit in-situ and remotely sensed carbon and ecosystem focused data products in the ABR. Together with simulations from Multi-scale Synthesis and Terrestrial Model Intercomparison Project (MsTMIP), we use these observations to evaluate the ability of models to capture soil carbon stocks and changes in the ABR. Specifically, we compare simulated versus observed soil carbon residence times in order to evaluate the functional response and sensitivity of modeled soil carbon stocks to changes in key environmental drivers. Understanding how simulated carbon residence time compares with observations and what drives these differences is critical for improving projections of changing carbon dynamics in the ABR and globally.

  19. ABR - Home

    Science.gov Websites

    Argonne National Laboratory Applied Battery Research for Transportation Program DOE Logo Home ; ABR > About ABR Projects News cell fabrication faciity posttest facility MERF Cell Fabrication Facility Post-Test Facility Materials Engineering Research Facility Battery News Recent Reports Funding

  20. Transcriptional regulation of drought response: a tortuous network of transcriptional factors

    PubMed Central

    Singh, Dhriti; Laxmi, Ashverya

    2015-01-01

    Drought is one of the leading factors responsible for the reduction in crop yield worldwide. Due to climate change, in future, more areas are going to be affected by drought and for prolonged periods. Therefore, understanding the mechanisms underlying the drought response is one of the major scientific concerns for improving crop yield. Plants deploy diverse strategies and mechanisms to respond and tolerate drought stress. Expression of numerous genes is modulated in different plants under drought stress that help them to optimize their growth and development. Plant hormone abscisic acid (ABA) plays a major role in plant response and tolerance by regulating the expression of many genes under drought stress. Transcription factors being the major regulator of gene expression play a crucial role in stress response. ABA regulates the expression of most of the target genes through ABA-responsive element (ABRE) binding protein/ABRE binding factor (AREB/ABF) transcription factors. Genes regulated by AREB/ABFs constitute a regulon termed as AREB/ABF regulon. In addition to this, drought responsive genes are also regulated by ABA-independent mechanisms. In ABA-independent regulation, dehydration-responsive element binding protein (DREB), NAM, ATAF, and CUC regulons play an important role by regulating many drought-responsive genes. Apart from these major regulons, MYB/MYC, WRKY, and nuclear factor-Y (NF-Y) transcription factors are also involved in drought response and tolerance. Our understanding about transcriptional regulation of drought is still evolving. Recent reports have suggested the existence of crosstalk between different transcription factors operating under drought stress. In this article, we have reviewed various regulons working under drought stress and their crosstalk with each other. PMID:26579147

  1. Measuring hearing in the harbor seal (Phoca vitulina): Comparison of behavioral and auditory brainstem response techniques

    NASA Astrophysics Data System (ADS)

    Wolski, Lawrence F.; Anderson, Rindy C.; Bowles, Ann E.; Yochem, Pamela K.

    2003-01-01

    Auditory brainstem response (ABR) and standard behavioral methods were compared by measuring in-air audiograms for an adult female harbor seal (Phoca vitulina). Behavioral audiograms were obtained using two techniques: the method of constant stimuli and the staircase method. Sensitivity was tested from 0.250 to 30 kHz. The seal showed good sensitivity from 6 to 12 kHz [best sensitivity 8.1 dB (re 20 μPa2.s) RMS at 8 kHz]. The staircase method yielded thresholds that were lower by 10 dB on average than the method of constant stimuli. ABRs were recorded at 2, 4, 8, 16, and 22 kHz and showed a similar best range (8-16 kHz). ABR thresholds averaged 5.7 dB higher than behavioral thresholds at 2, 4, and 8 kHz. ABRs were at least 7 dB lower at 16 kHz, and approximately 3 dB higher at 22 kHz. The better sensitivity of ABRs at higher frequencies could have reflected differences in the seal's behavior during ABR testing and/or bandwidth characteristics of test stimuli. These results agree with comparisons of ABR and behavioral methods performed in other recent studies and indicate that ABR methods represent a good alternative for estimating hearing range and sensitivity in pinnipeds, particularly when time is a critical factor and animals are untrained.

  2. Input and output compensation for the cochlear traveling wave delay in wide-band ABR recordings: implications for small acoustic tumor detection.

    PubMed

    Don, Manuel; Elberling, Claus; Maloff, Erin

    2009-02-01

    The Stacked ABR (auditory brainstem response) attempts at the output of the auditory periphery to compensate for the temporal dispersion of neural activation caused by the cochlear traveling wave in response to click stimulation. Compensation can also be made at the input by using a chirp stimulus. It has been demonstrated that the Stacked ABR is sensitive to small tumors that are often missed by standard ABR latency measures. Because a chirp stimulus requires only a single data acquisition run whereas the Stacked ABR requires six, we try to evaluate some indirect evidence justifying the use of a chirp for small tumor detection. We compared the sensitivity and specificity of different Stacked ABRs formed by aligning the derived-band ABRs according to (1) the individual's peak latencies, (2) the group mean latencies, and (3) the modeled latencies used to develop a chirp. For tumor detection with a chosen sensitivity of 95%, a relatively high specificity of 85% may be achieved with a chirp. It appears worthwhile to explore the actual use of a chirp because significantly shorter test and analysis times might be possible.

  3. Attenuation of Progressive Hearing Loss in DBA/2J Mice by Reagents that Affect Epigenetic Modifications Is Associated with Up-Regulation of the Zinc Importer Zip4

    PubMed Central

    Mutai, Hideki; Miya, Fuyuki; Fujii, Masato; Tsunoda, Tatsuhiko; Matsunaga, Tatsuo

    2015-01-01

    Various factors that are important for proper hearing have been identified, including serum levels of zinc. Here we investigated whether epigenetic regulatory pathways, which can be modified by environmental factors, could modulate hearing. RT-PCR detected expression of genes encoding DNA methyltransferase and histone deacetylase (Hdac) in the postnatal as well as adult mouse auditory epithelium. DBA/2J mice, which are a model for progressive hearing loss, were injected subcutaneously with one or a combination of the following reagents: L-methionine as a methyl donor, valproic acid as a pan-Hdac inhibitor, and folic acid and vitamin B12 as putative factors involved in age-related hearing loss. The mice were treated from ages 4 to 12 weeks (N ≥ 5), and auditory brainstem response (ABR) thresholds were measured at 8, 16, and 32 kHz. Treatment of the mice with a combination of L-methionine and valproic acid (M+V) significantly reduced the increase in the ABR threshold at 32 kHz. Treatment with any of these reagents individually produced no such effect. Microarray analyses detected 299 gene probes that were significantly up- or down-regulated in the cochleae of mice treated with M+V compared with the control vehicle-treated mice. Quantitative RT-PCR confirmed significant up-regulation of a zinc importer gene, Zip4, in the cochleae of mice treated with M+V. Immunohistochemistry demonstrated an intense Zip4 signal in cochlear tissues such as the lateral wall, organ of Corti, and spiral ganglion. Finally, mice treated with the Zip4 inducer (–)-epigallocatechin-3-O-gallate showed a significant reduction in the increase of the ABR threshold at 32 kHz and up-regulation of Zip4 expression in the cochlea. This study suggests that epigenetic regulatory pathways can modify auditory function and that zinc intake in the cochlea via Zip4 mediates maintenance of mammalian hearing. PMID:25875282

  4. Biological Imaging Capability in the ABRS Facility on ISS

    NASA Technical Reports Server (NTRS)

    Cox, David R.; Murdoch, T.; Regan, M. F.; Meshlberger, R. J.; Mortenson, T. E.; Albino, S. A.; Paul, A. L.; Ferl, R. J.

    2010-01-01

    This slide presentation reviews the Advanced Biological Research System (ABRS) on the International Space Station (ISS) and its biological imaging capability. The ABRS is an environmental control chamber. It has two indpendently controlled Experiment Research Chambers (ERCs) with temperature, relative humidity and carbon dioxide controls. ABRS is a third generation plant growth system. Several experiments are reviewed, with particular interest in the use of Green Fluorescent Protein (GFP) a non-destructive plant stress reporting mechanism, naturally found in jellyfish.

  5. Analysis of Brain Recurrence

    NASA Astrophysics Data System (ADS)

    Frilot, Clifton; Kim, Paul Y.; Carrubba, Simona; McCarty, David E.; Chesson, Andrew L.; Marino, Andrew A.

    Analysis of Brain Recurrence (ABR) is a method for extracting physiologically significant information from the electroencephalogram (EEG), a non-stationary electrical output of the brain, the ultimate complex dynamical system. ABR permits quantification of temporal patterns in the EEG produced by the non-autonomous differential laws that govern brain metabolism. In the context of appropriate experimental and statistical designs, ABR is ideally suited to the task of interpreting the EEG. Present applications of ABR include discovery of a human magnetic sense, increased mechanistic understanding of neuronal membrane processes, diagnosis of degenerative neurological disease, detection of changes in brain metabolism caused by weak environmental electromagnetic fields, objective characterization of the quality of human sleep, and evaluation of sleep disorders. ABR has important beneficial implications for the development of clinical and experimental neuroscience.

  6. Bone-Conduction ABR Tests.

    ERIC Educational Resources Information Center

    Cone-Wesson, Barbara

    1995-01-01

    This article discusses the accuracy of bone-conduction auditory brainstem response (BC-ABR) tests to determine the presence and severity of conductive hearing impairment. It provides warnings about technical pitfalls and recommends incorporating BC-ABR protocols for routine clinical use. It concludes that the method allows estimating cochlear…

  7. 75 FR 22172 - Notice of Projects Approved for Consumptive Uses of Water

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-27

    ... Corporation, Pad ID: Procter & Gamble Mehoopany Plant 4V, ABR-20100125, Washington Township, Wyoming County... Corporation, Pad ID: Procter & Gamble Mehoopany Plant 3V, ABR-20100126, Washington Township, Wyoming County... Corporation, Pad ID: Procter & Gamble Mehoopany Plant 5V, ABR-20100127, Washington Township, Wyoming County...

  8. Comparison of distortion product otoacoustic emissions with auditory brain-stem response for clinical use in neonatal intensive care unit.

    PubMed

    Ochi, A; Yasuhara, A; Kobayashi, Y

    1998-11-01

    This study compares the clinical usefulness of distortion product otoacoustic emissions (DPOAEs) with the auditory brain-stem response (ABR) for neonates in the neonatal intensive care unit for the evaluation of hearing impairment. Both DPOAEs and ABR were performed on 36 neonates (67 ears) on the same day. We defined neonates as having normal hearing when the thresholds of wave V of ABR were < or =45 dB hearing level. (1) We could not obtain DPOAEs at f2 = 977 Hz in neonates with normal hearing because of high noise floors. DPOAE recording time was 36 min shorter than that of ABR. (2) We defined as normal DPOAEs, the number of frequencies which showed the DPgram-noise floor > or =4 dB was > or =4 at 6 f2 frequencies, from 1416 Hz to 7959 Hz. (3) Normal thresholds of ABR and normal DPOAEs showed the same percentages, i.e. 68.7%, but the percentage of different results between ABR and DPOAEs was 6.0%. Our study indicates that DPOAEs represent a simple procedure, which can be easily performed in the NICU to obtain reliable results in high-risk neonates. Results obtained by DPOAEs were comparable to those obtained by the more complex procedure of ABR.

  9. Subcortical encoding of speech cues in children with attention deficit hyperactivity disorder.

    PubMed

    Jafari, Zahra; Malayeri, Saeed; Rostami, Reza

    2015-02-01

    There is little information about processing of nonspeech and speech stimuli at the subcortical level in individuals with attention deficit hyperactivity disorder (ADHD). The auditory brainstem response (ABR) provides information about the function of the auditory brainstem pathways. We aim to investigate the subcortical function in neural encoding of click and speech stimuli in children with ADHD. The subjects include 50 children with ADHD and 34 typically developing (TD) children between the ages of 8 and 12 years. Click ABR (cABR) and speech ABR (sABR) with 40 ms synthetic /da/ syllable stimulus were recorded. Latencies of cABR in waves of III and V and duration of V-Vn (P⩽0.027), and latencies of sABR in waves A, D, E, F and O and duration of V-A (P⩽0.034) were significantly longer in children with ADHD than in TD children. There were no apparent differences in components the sustained frequency following response (FFR). We conclude that children with ADHD have deficits in temporal neural encoding of both nonspeech and speech stimuli. There is a common dysfunction in the processing of click and speech stimuli at the brainstem level in children with suspected ADHD. Copyright © 2015. Published by Elsevier Ireland Ltd.

  10. Association Between Sex and Speech Auditory Brainstem Responses in Adults, and Relationship to Sex Hormone Levels.

    PubMed

    Liu, Jinfeng; Wang, Dan; Li, Xiaoting; Ningyu, Wang

    2017-05-14

    BACKGROUND The aim of this study was to investigate the association between sex and speech-ABR in adults, and its relationship to sex hormone levels. MATERIAL AND METHODS Speech-ABR were elicited with the consonant-vowel syllable (/da/) in a total of 35 adults. Reproductive hormone levels were also measured. RESULTS The transient response of the speech-ABR (waves V, A, and O) in females show a shorter latency (waves V, A and O) and a larger amplitude (waves V and A) than in males (P<0.05), except for the amplitude of peak O (P>0.05). The sustained response of females exhibited a larger amplitude (wave F, P<0.05) and a shorter latency (wave D, E, and F, P<0.05) than in males, except for the amplitude of peak D and E (P>0.05). The latencies of speech-ABR were positively correlated with testosterone level (P<0.05), and were negatively correlated with estradiol (E2) levels (P<0.05), except for wave E (P>0.05). The E2 showed a positive correlation with the absolute value of amplitude of the speech-ABR (P < 0.05). On the contrary, total testosterone showed a negative correlation with the absolute value of amplitude the speech-ABR (P<0.05), except for wave D and wave O (P>0.05). CONCLUSIONS Sex differences in speech-ABR are significant in adults. The latencies and amplitude of the speech-ABR waves were correlated with the E2 concentration and testosterone level. The sex hormones likely affect speech encoding in the brainstem.

  11. Newborn Auditory Brainstem Evoked Responses (ABRs): Prenatal and Contemporary Correlates.

    ERIC Educational Resources Information Center

    Murray, Ann D.

    1988-01-01

    Presented are a literature review and new data on correlates of newborn auditory brainstem evoked responses (ABRs). Concludes that disorders of the central components of the ABR may be more of prenatal than of postnatal origin. The I-V interval had low but reliable correlations with four of 11 Brazelton scale variables. (RH)

  12. 76 FR 33019 - Notice of Projects Approved for Consumptive Uses of Water

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-07

    ..., 2011. 10. Aruba Petroleum, Inc., Pad ID: Lundy Well Pad, ABR-201103010, Gamble Township, Lycoming...-- 4H Drilling Pad, ABR-201104012, Gamble Township, Lycoming County, Pa.; Consumptive Use of up to 5.000...-- 4H Drilling Pad, ABR-201104013, Gamble Township, Lycoming County, Pa.; Consumptive Use of up to 5.000...

  13. Phase stability analysis of chirp evoked auditory brainstem responses by Gabor frame operators.

    PubMed

    Corona-Strauss, Farah I; Delb, Wolfgang; Schick, Bernhard; Strauss, Daniel J

    2009-12-01

    We have recently shown that click evoked auditory brainstem responses (ABRs) can be efficiently processed using a novelty detection paradigm. Here, ABRs as a large-scale reflection of a stimulus locked neuronal group synchronization at the brainstem level are detected as novel instance-novel as compared to the spontaneous activity which does not exhibit a regular stimulus locked synchronization. In this paper we propose for the first time Gabor frame operators as an efficient feature extraction technique for ABR single sweep sequences that is in line with this paradigm. In particular, we use this decomposition technique to derive the Gabor frame phase stability (GFPS) of sweep sequences of click and chirp evoked ABRs. We show that the GFPS of chirp evoked ABRs provides a stable discrimination of the spontaneous activity from stimulations above the hearing threshold with a small number of sweeps, even at low stimulation intensities. It is concluded that the GFPS analysis represents a robust feature extraction method for ABR single sweep sequences. Further studies are necessary to evaluate the value of the presented approach for clinical applications.

  14. Auditory brain stem response and cortical evoked potentials in children with type 1 diabetes mellitus.

    PubMed

    Radwan, Heba Mohammed; El-Gharib, Amani Mohamed; Erfan, Adel Ali; Emara, Afaf Ahmad

    2017-05-01

    Delay in ABR and CAEPs wave latencies in children with type 1DM indicates that there is abnormality in the neural conduction in DM patients. The duration of DM has greater effect on auditory function than the control of DM. Diabetes mellitus (DM) is a common endocrine and metabolic disorder. Evoked potentials offer the possibility to perform a functional evaluation of neural pathways in the central nervous system. To investigate the effect of type 1 diabetes mellitus (T1DM) on auditory brain stem response (ABR) and cortical evoked potentials (CAEPs). This study included two groups: a control group (GI), which consisted of 20 healthy children with normal peripheral hearing, and a study group (GII), which consisted of 30 children with type I DM. Basic audiological evaluation, ABR, and CAEPs were done in both groups. Delayed absolute latencies of ABR and CAEPs waves were found. Amplitudes showed no significant difference between both groups. Positive correlation was found between ABR wave latencies and duration of DM. No correlation was found between ABR, CAEPs, and glycated hemoglobin.

  15. Human, animal and environmental contributors to antibiotic resistance in low-resource settings: integrating behavioural, epidemiological and One Health approaches

    PubMed Central

    Unicomb, Leanne; Islam, Mohammad Aminul

    2018-01-01

    Antibiotic resistance (ABR) is recognized as a One Health challenge because of the rapid emergence and dissemination of resistant bacteria and genes among humans, animals and the environment on a global scale. However, there is a paucity of research assessing ABR contemporaneously in humans, animals and the environment in low-resource settings. This critical review seeks to identify the extent of One Health research on ABR in low- and middle-income countries (LMICs). Existing research has highlighted hotspots for environmental contamination; food-animal production systems that are likely to harbour reservoirs or promote transmission of ABR as well as high and increasing human rates of colonization with ABR commensal bacteria such as Escherichia coli. However, very few studies have integrated all three components of the One Health spectrum to understand the dynamics of transmission and the prevalence of community-acquired resistance in humans and animals. Microbiological, epidemiological and social science research is needed at community and population levels across the One Health spectrum in order to fill the large gaps in knowledge of ABR in low-resource settings. PMID:29643217

  16. Integration of Metabolic and Quorum Sensing Signals Governing the Decision to Cooperate in a Bacterial Social Trait

    PubMed Central

    Boyle, Kerry E.; Monaco, Hilary; van Ditmarsch, Dave; Deforet, Maxime; Xavier, Joao B.

    2015-01-01

    Many unicellular organisms live in multicellular communities that rely on cooperation between cells. However, cooperative traits are vulnerable to exploitation by non-cooperators (cheaters). We expand our understanding of the molecular mechanisms that allow multicellular systems to remain robust in the face of cheating by dissecting the dynamic regulation of cooperative rhamnolipids required for swarming in Pseudomonas aeruginosa. We combine mathematical modeling and experiments to quantitatively characterize the integration of metabolic and population density signals (quorum sensing) governing expression of the rhamnolipid synthesis operon rhlAB. The combined computational/experimental analysis reveals that when nutrients are abundant, rhlAB promoter activity increases gradually in a density dependent way. When growth slows down due to nutrient limitation, rhlAB promoter activity can stop abruptly, decrease gradually or even increase depending on whether the growth-limiting nutrient is the carbon source, nitrogen source or iron. Starvation by specific nutrients drives growth on intracellular nutrient pools as well as the qualitative rhlAB promoter response, which itself is modulated by quorum sensing. Our quantitative analysis suggests a supply-driven activation that integrates metabolic prudence with quorum sensing in a non-digital manner and allows P. aeruginosa cells to invest in cooperation only when the population size is large enough (quorum sensing) and individual cells have enough metabolic resources to do so (metabolic prudence). Thus, the quantitative description of rhlAB regulatory dynamics brings a greater understating to the regulation required to make swarming cooperation stable. PMID:26102206

  17. Will available bit rate (ABR) services give us the capability to offer virtual LANs over wide-area ATM networks?

    NASA Astrophysics Data System (ADS)

    Ferrandiz, Ana; Scallan, Gavin

    1995-10-01

    The available bit rate (ABR) service allows connections to exceed their negotiated data rates during the life of the connections when excess capacity is available in the network. These connections are subject to flow control from the network in the event of network congestion. The ability to dynamically adjust the data rate of the connection can provide improved utilization of the network and be a valuable service to end users. ABR type service is therefore appropriate for the transmission of bursty LAN traffic over a wide area network in a manner that is more efficient and cost effective than allocating bandwdith at the peak cell rate. This paper describes the ABR service and discusses if it is realistic to operate a LAN like service over a wide area using ABR.

  18. The Auditory-Brainstem Response to Continuous, Non-repetitive Speech Is Modulated by the Speech Envelope and Reflects Speech Processing

    PubMed Central

    Reichenbach, Chagit S.; Braiman, Chananel; Schiff, Nicholas D.; Hudspeth, A. J.; Reichenbach, Tobias

    2016-01-01

    The auditory-brainstem response (ABR) to short and simple acoustical signals is an important clinical tool used to diagnose the integrity of the brainstem. The ABR is also employed to investigate the auditory brainstem in a multitude of tasks related to hearing, such as processing speech or selectively focusing on one speaker in a noisy environment. Such research measures the response of the brainstem to short speech signals such as vowels or words. Because the voltage signal of the ABR has a tiny amplitude, several hundred to a thousand repetitions of the acoustic signal are needed to obtain a reliable response. The large number of repetitions poses a challenge to assessing cognitive functions due to neural adaptation. Here we show that continuous, non-repetitive speech, lasting several minutes, may be employed to measure the ABR. Because the speech is not repeated during the experiment, the precise temporal form of the ABR cannot be determined. We show, however, that important structural features of the ABR can nevertheless be inferred. In particular, the brainstem responds at the fundamental frequency of the speech signal, and this response is modulated by the envelope of the voiced parts of speech. We accordingly introduce a novel measure that assesses the ABR as modulated by the speech envelope, at the fundamental frequency of speech and at the characteristic latency of the response. This measure has a high signal-to-noise ratio and can hence be employed effectively to measure the ABR to continuous speech. We use this novel measure to show that the ABR is weaker to intelligible speech than to unintelligible, time-reversed speech. The methods presented here can be employed for further research on speech processing in the auditory brainstem and can lead to the development of future clinical diagnosis of brainstem function. PMID:27303286

  19. Validation of DPOAE screening conducted by village health workers in a rural community with real-time click evoked tele-auditory brainstem response.

    PubMed

    Ramkumar, Vidya; Vanaja, C S; Hall, James W; Selvakumar, K; Nagarajan, Roopa

    2018-05-01

    This study assessed the validity of DPOAE screening conducted by village health workers (VHWs) in a rural community. Real-time click evoked tele-auditory brainstem response (tele-ABR) was used as the gold standard to establish validity. A cross-sectional design was utilised to compare the results of screening by VHWs to those obtained via tele-ABR. Study samples: One hundred and nineteen subjects (0 to 5 years) were selected randomly from a sample of 2880 infants and young children who received DPOAE screening by VHWs. Real time tele-ABR was conducted by using satellite or broadband internet connectivity at the village. An audiologist located at the tertiary care hospital conducted tele-ABR testing through a remote computing paradigm. Tele-ABR was recorded using standard recording parameters recommended for infants and young children. Wave morphology, repeatability and peak latency data were used for ABR analysis. Tele-ABR and DPOAE findings were compared for 197 ears. The sensitivity of DPOAE screening conducted by the VHW was 75%, and specificity was 91%. The negative and positive predictive values were 98.8% and 27.2%, respectively. The validity of DPOAE screening conducted by trained VHW was acceptable. This study supports the engagement of grass-root workers in community-based hearing health care provision.

  20. Auditory Brainstem Response Thresholds to Air- and Bone-Conducted CE-Chirps in Neonates and Adults.

    PubMed

    Cobb, Kensi M; Stuart, Andrew

    2016-08-01

    The purpose of this study was to compare auditory brainstem response (ABR) thresholds to air- and bone-conducted CE-Chirps in neonates and adults. Thirty-two neonates with no physical or neurologic challenges and 20 adults with normal hearing participated. ABRs were acquired with a starting intensity of 30 dB normal hearing level (nHL). The lowest stimulus intensity level at which a wave V was identifiable and replicable was considered the ABR threshold. ABR thresholds to air-conducted CE-Chirps were 9.8 dB nHL for neonates and adults. ABR thresholds to bone-conducted CE-Chirps were 3.8 and 13.8 dB nHL for neonates and adults, respectively. The difference in ABR thresholds to bone-conducted CE-Chirps was significantly different (p < .0001, ηp2 = .45). Adults had significantly larger wave V amplitudes to air- (p < .0001, ηp2 = .50) and bone-conducted (p = .013, ηp2 = .15) CE-Chirps at a stimulus intensity of 30 dB nHL. At the same intensity, adults evidenced significantly shorter wave V latencies (p < .0001, ηp2 = .49) only with air-conducted CE-chirps. The difference in ABR thresholds and wave V latencies to air- and bone-conducted CE-Chirps between neonates and adults may be attributed to a disparity in effective signal delivery to the cochlea.

  1. Screening the High-Risk Newborn for Hearing Loss: The Crib-O-Gram v the Auditory Brainstem Response.

    ERIC Educational Resources Information Center

    Cox, L. Clarke

    1988-01-01

    Presented are a rationale for identifying hearing loss in infancy and a history of screening procedures. The Crib-O-Gram and auditory brainstem response (ABR) tests are evaluated for reliability, validity, and cost-effectiveness. The ABR is recommended, and fully automated ABR instrumentation, which lowers expenses for trained personnel and…

  2. Canadian guidelines for acute bacterial rhinosinusitis

    PubMed Central

    Kaplan, Alan

    2014-01-01

    Objective To provide a clinical summary of the Canadian clinical practice guidelines for acute bacterial rhinosinusitis (ABRS) that includes relevant considerations for family physicians. Quality of evidence Guideline authors performed a systematic literature search and drafted recommendations. Recommendations received both strength of evidence and strength of recommendation ratings. Input from external content experts was sought, as was endorsement from Canadian medical societies (Association of Medical Microbiology and Infectious Disease Canada, Canadian Society of Allergy and Clinical Immunology, Canadian Society of Otolaryngology—Head and Neck Surgery, Canadian Association of Emergency Physicians, and the Family Physicians Airways Group of Canada). Main message Diagnosis of ABRS is based on the presence of specific symptoms and their duration; imaging or culture are not needed in uncomplicated cases. Treatment is dependent on symptom severity, with intranasal corticosteroids (INCSs) recommended as monotherapy for mild and moderate cases, although the benefit might be modest. Use of INCSs plus antibiotics is reserved for patients who fail to respond to INCSs after 72 hours, and for initial treatment of patients with severe symptoms. Antibiotic selection must account for the suspected pathogen, the risk of resistance, comorbid conditions, and local antimicrobial resistance trends. Adjunct therapies such as nasal saline irrigation are recommended. Failure to respond to treatment, recurrent episodes, and signs of complications should prompt referral to an otolaryngologist. The guidelines address situations unique to the Canadian health care environment, including actions to take during prolonged wait periods for specialist referral or imaging. Conclusion The Canadian guidelines provide up-to-date recommendations for diagnosis and treatment of ABRS that reflect an evolving understanding of the disease. In addition, the guidelines offer useful tools to help clinicians discern viral from bacterial episodes, as well as optimally manage their patients with ABRS. PMID:24627376

  3. Auditory brainstem evoked responses and temperature monitoring during pediatric cardiopulmonary bypass.

    PubMed

    Rodriguez, R A; Edmonds, H L; Auden, S M; Austin, E H

    1999-09-01

    To examine the effects of temperature on auditory brainstem responses (ABRs) in infants during hypothermic cardiopulmonary bypass for total circulatory arrest (TCA). The relationship between ABRs (as a surrogate measure of core-brain temperature) and body temperature as measured at several temperature monitoring sites was determined. In a prospective, observational study, ABRs were recorded non-invasively at normothermia and at every 1 or 2 degrees C change in ear-canal temperature during cooling and rewarming in 15 infants (ages: 2 days to 14 months) that required TCA. The ABR latencies and amplitudes and the lowest temperatures at which an ABR was identified (the threshold) were measured during both cooling and rewarming. Temperatures from four standard temperature monitoring sites were simultaneously recorded. The latencies of ABRs increased and amplitudes decreased with cooling (P < 0.01), but rewarming reversed these effects. The ABR threshold temperature as related to each monitoring site (ear-canal, nasopharynx, esophagus and bladder) was respectively determined as 23 +/- 2.2 degrees C, 20.8 +/- 1.7 degrees C, 14.6 +/- 3.4 degrees C, and 21.5 +/- 3.8 degrees C during cooling and 21.8 +/- 1.6 degrees C, 22.4 +/- 2.0 degrees C, 27.6 +/- 3.6 degrees C, and 23.0 +/- 2.4 degrees C during rewarming. The rewarming latencies were shorter and Q10 latencies smaller than the corresponding cooling values (P < 0.01). Esophageal and bladder sites were more susceptible to temperature variations as compared with the ear-canal and nasopharynx. No temperature site reliably predicted an electrophysiological threshold. A faster latency recovery during rewarming suggests that body temperature monitoring underestimates the effects of rewarming in the core-brain. ABRs may be helpful to monitor the effects of cooling and rewarming on the core-brain during pediatric cardiopulmonary bypass.

  4. An Analysis of The Parameters Used In Speech ABR Assessment Protocols.

    PubMed

    Sanfins, Milaine D; Hatzopoulos, Stavros; Donadon, Caroline; Diniz, Thais A; Borges, Leticia R; Skarzynski, Piotr H; Colella-Santos, Maria Francisca

    2018-04-01

    The aim of this study was to assess the parameters of choice, such as duration, intensity, rate, polarity, number of sweeps, window length, stimulated ear, fundamental frequency, first formant, and second formant, from previously published speech ABR studies. To identify candidate articles, five databases were assessed using the following keyword descriptors: speech ABR, ABR-speech, speech auditory brainstem response, auditory evoked potential to speech, speech-evoked brainstem response, and complex sounds. The search identified 1288 articles published between 2005 and 2015. After filtering the total number of papers according to the inclusion and exclusion criteria, 21 studies were selected. Analyzing the protocol details used in 21 studies suggested that there is no consensus to date on a speech-ABR protocol and that the parameters of analysis used are quite variable between studies. This inhibits the wider generalization and extrapolation of data across languages and studies.

  5. Human, animal and environmental contributors to antibiotic resistance in low-resource settings: integrating behavioural, epidemiological and One Health approaches.

    PubMed

    Rousham, Emily K; Unicomb, Leanne; Islam, Mohammad Aminul

    2018-04-11

    Antibiotic resistance (ABR) is recognized as a One Health challenge because of the rapid emergence and dissemination of resistant bacteria and genes among humans, animals and the environment on a global scale. However, there is a paucity of research assessing ABR contemporaneously in humans, animals and the environment in low-resource settings. This critical review seeks to identify the extent of One Health research on ABR in low- and middle-income countries (LMICs). Existing research has highlighted hotspots for environmental contamination; food-animal production systems that are likely to harbour reservoirs or promote transmission of ABR as well as high and increasing human rates of colonization with ABR commensal bacteria such as Escherichia coli However, very few studies have integrated all three components of the One Health spectrum to understand the dynamics of transmission and the prevalence of community-acquired resistance in humans and animals. Microbiological, epidemiological and social science research is needed at community and population levels across the One Health spectrum in order to fill the large gaps in knowledge of ABR in low-resource settings. © 2018 The Author(s).

  6. Enhanced decolorization of azo dye in a small pilot-scale anaerobic baffled reactor coupled with biocatalyzed electrolysis system (ABR-BES): a design suitable for scaling-up.

    PubMed

    Cui, Dan; Guo, Yu-Qi; Lee, Hyung-Sool; Wu, Wei-Min; Liang, Bin; Wang, Ai-Jie; Cheng, Hao-Yi

    2014-07-01

    A four-compartment anaerobic baffled reactor (ABR) incorporated with membrane-less biocatalyzed electrolysis system (BES) was tested for the treatment of azo dye (alizarin yellow R, AYR) wastewater (AYR, 200 mg L(-1); glucose, 1000 mg L(-1)). The ABR-BES was operated without and with external power supply to examine AYR reduction process and reductive intermediates with different external voltages (0.3, 0.5 and 0.7 V) and hydraulic retention times (HRT: 8, 6 and 4h). The decolorization efficiency in the ABR-BES (8h HRT, 0.5 V) was higher than that in ABR-BES without electrolysis, i.e. 95.1 ± 1.5% versus 86.9 ± 6.3%. Incorporation of BES with ABR accelerated the consumption of VFAs (mainly acetate) and attenuated biogas (methane) production. Higher power supply (0.7 V) enhanced AYR decolorization efficiency (96.4 ± 1.8%), VFAs removal, and current density (24.1 Am(-3) TCV). Shorter HRT increased volumetric AYR decolorization rates, but decreased AYR decolorization efficiency. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Acetylcholinesterase and acetylcholine receptor. Final report, 1 April 1992-30 September 1995

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

    Cohen, S.G.

    1995-10-01

    1 Bromo-214Cpinacolone (34CbrPin) inactivates AcChEs, from T. nobiliana labeling Cys 231, and E. electricus labeling His-440, and possibly Trp-435 and Asn-533. 14Cphenacyl bromide, (14CphABr) inactivates, labeling Cys-231 and His-550 in T. nobiliana, and His-550 in E. electricus. Five sequenced peptides in T. nobiliana, are identical with those from T. califomica. Four peptides from E. electricus show 77 - 96% homology. Inactivations by BrPin or PhABr exclude 3Hdfp; inactivation by DFP does not exclude 14CbrPin or 14CphABr. In studies with 14CbrPin, 5-trimethylammonio-2-pentanone was the preferred protecting agent; with 14CphABr, 3-trimethylammonioacetophenone was used with T. nobiliana, phenyltrimethylammonium ion with E. electricus. N-Methylacridiniummore » protects E. electricus against PhABr, but accelerates inactivation of T. nobiliana. Acetylcholine protects E. electricus against PhABr, indicating that His-550 marks the site at which the binding of high concentration of the substrate inhibits its own hydrolysis, possibly important in its action as a neurotransmitter. Photolysis of pivalophenone leading to benzoyl and tert-butyl radicals, inactivates the enzymes. Protection is offered by radical scavenging thiols.« less

  8. CalA, a Cyanobacterial AbrB Protein, Interacts with the Upstream Region of hypC and Acts as a Repressor of Its Transcription in the Cyanobacterium Nostoc sp. Strain PCC 7120▿ †

    PubMed Central

    Agervald, Åsa; Zhang, Xiaohui; Stensjö, Karin; Devine, Ellenor; Lindblad, Peter

    2010-01-01

    The filamentous, heterocystous, nitrogen-fixing cyanobacterium Nostoc sp. strain PCC 7120 may contain, depending on growth conditions, up to two hydrogenases directly involved in hydrogen metabolism. HypC is one out of at least seven auxiliary gene products required for synthesis of a functional hydrogenase, specifically involved in the maturation of the large subunit. In this study we present a protein, CalA (Alr0946 in the genome), belonging to the transcription regulator family AbrB, which in protein-DNA assays was found to interact with the upstream region of hypC. Transcriptional investigations showed that calA is cotranscribed with the downstream gene alr0947, which encodes a putative protease from the abortive infection superfamily, Abi. CalA was shown to interact specifically not only with the upstream region of hypC but also with its own upstream region, acting as a repressor on hypC. The bidirectional hydrogenase activity was significantly downregulated when CalA was overexpressed, demonstrating a correlation with the transcription factor, either direct or indirect. In silico studies showed that homologues to both CalA and Alr0947 are highly conserved proteins within cyanobacteria with very similar physical organizations of the corresponding structural genes. Possible functions of the cotranscribed downstream protein Alr0947 are presented. In addition, we present a three-dimensional (3D) model of the DNA binding domain of CalA and putative DNA binding mechanisms are discussed. PMID:20023111

  9. Evidence for Atypical Auditory Brainstem Responses in Young Children with Suspected Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Roth, Daphne Ari-Even; Muchnik, Chava; Shabtai, Esther; Hildesheimer, Minka; Henkin, Yael

    2012-01-01

    Aim: The aim of this study was to characterize the auditory brainstem responses (ABRs) of young children with suspected autism spectrum disorders (ASDs) and compare them with the ABRs of children with language delay and with clinical norms. Method: The ABRs of 26 children with suspected ASDs (21 males, five females; mean age 32.5 mo) and an age-…

  10. Auditory function in normal-hearing, noise-exposed human ears

    PubMed Central

    Stamper, Greta C.; Johnson, Tiffany A.

    2014-01-01

    Objectives To determine if supra-threshold measures of auditory function, such as distortion-product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs), are correlated with noise exposure history in normal-hearing human ears. Recent data from animal studies have revealed significant deafferentation of auditory nerve fibers following full recovery from temporary noise-induced hearing loss (NIHL). Furthermore, these data report smaller ABR wave I amplitudes in noise-exposed animal ears when compared to non-noise exposed control animals or pre-noise exposure amplitudes in the same animal. It is unknown if a similar phenomenon exists in the normal-hearing, noise-exposed human ear. Design Thirty normal-hearing human subjects with a range of noise exposure backgrounds (NEBs) participated in this study. NEB was quantified by the use of a noise exposure questionnaire that extensively queried loud sound exposure over the previous 12 months. DPOAEs were collected at three f2’s (1, 2, and 4 kHz) over a range of L2’s. DPOAE stimulus level began at 80 dB FPL (forward-pressure level) and decreased in 10 dB steps. Two-channel ABRs were collected in response to click stimuli and 4 kHz tone bursts; one channel utilized an ipsilateral mastoid electrode and the other an ipsilateral tympanic membrane (TM) electrode. ABR stimulus level began at 90 dB nHL and was decreased in 10 dB steps. Amplitudes of waves I and V of the ABR were analyzed. Results A statistically significant relationship between ABR wave I amplitude and NEB was found for clicked-evoked ABRs recorded at a stimulus level of 90 dB nHL using a mastoid recording electrode. For this condition, ABR wave I amplitudes decreased as a function of NEB. Similar systematic trends were present for ABRs collected in response to clicks and 4 kHz tone bursts at additional supra-threshold stimulation levels (≥ 70 dB nHL). The relationship weakened and disappeared with decreases in stimulation level (≤ 60 dB nHL). Similar patterns were present for ABRs collected using a TM electrode. However, these relationships were not statistically significant and were weaker and more variable than those collected using a mastoid electrode. In contrast to the findings for ABR wave I, wave V amplitude was not significantly related to NEB. Furthermore, there was no evidence of a systematic relationship between supra-threshold DPOAEs and NEB. Conclusions A systematic trend of smaller ABR wave I amplitudes was found in normal-hearing human ears with greater amounts of voluntary NEB in response to supra-threshold clicks and 4 kHz tone bursts. These findings are consistent with data from previous work completed in animals, where the reduction in supra-threshold responses was a result of deafferentation of high-threshold/low-spontaneous rate auditory nerve fibers. These data suggest a similar mechanism might be operating in human ears following exposure to high sound levels. However, evidence of this damage is only apparent when examining supra-threshold wave I amplitude of the ABR. In contrast, supra-threshold DPOAE level was not significantly related to NEB. This was expected, given noise-induced auditory damage findings in animal ears did not extend to the outer hair cells, the generator for the DPOAE response. PMID:25350405

  11. Difference of auditory brainstem responses by stimulating to round and oval window in animal experiments.

    PubMed

    Lee, Jyung Hyun; Park, Hyo Soon; Wei, Qun; Kim, Myoung Nam; Cho, Jin-Ho

    2017-01-02

    ABSTACT To ensure the safety and efficacy of implantable hearing aids, animal experiments are an essential developmental procedure, in particular, auditory brainstem responses (ABRs) can be used to verify the objective effectiveness of implantable hearing aids. This study measured and compared the ABRs generated when applying the same vibration stimuli to an oval window and round window. The ABRs were measured using a TDT system 3 (TDT, USA), while the vibration stimuli were applied to a round window and oval window in 4 guinea pigs using a piezo-electric transducer with a proper contact tip. A paired t-test was used to determine any differences between the ABR amplitudes when applying the stimulation to an oval window and round window. The paired t-test revealed a significant difference between the ABR amplitudes generated by the round and oval window stimulation (t = 10.079, α < .0001). Therefore, the results confirmed that the biological response to round window stimulation was not the same as that to oval window stimulation.

  12. The modulation rate transfer function of a harbour porpoise (Phocoena phocoena).

    PubMed

    Linnenschmidt, Meike; Wahlberg, Magnus; Damsgaard Hansen, Janni

    2013-02-01

    During echolocation, toothed whales produce ultrasonic clicks at extremely rapid rates and listen for the returning echoes. The auditory brainstem response (ABR) duration was evaluated in terms of latency between single peaks: 5.5 ms (from peak I to VII), 3.4 ms (I-VI), and 1.4 ms (II-IV). In comparison to the killer whale and the bottlenose dolphin, the ABR of the harbour porpoise has shorter intervals between the peaks and consequently a shorter ABR duration. This indicates that the ABR duration and peak latencies are possibly related to the relative size of the auditory structures of the central nervous system and thus to the animal's size. The ABR to a sinusoidal amplitude modulated stimulus at 125 kHz (sensitivity threshold 63 dB re 1 μPa rms) was evaluated to determine the modulation rate transfer function of a harbour porpoise. The ABR showed distinct envelope following responses up to a modulation rate of 1,900 Hz. The corresponding calculated equivalent rectangular duration of 263 μs indicates a good temporal resolution in the harbour porpoise auditory system similar to the one for the bottlenose dolphin. The results explain how the harbour porpoise can follow clicks and echoes during echolocation with very short inter click intervals.

  13. Evidence of "hidden hearing loss" following noise exposures that produce robust TTS and ABR wave-I amplitude reductions.

    PubMed

    Lobarinas, Edward; Spankovich, Christopher; Le Prell, Colleen G

    2017-06-01

    In animals, noise exposures that produce robust temporary threshold shifts (TTS) can produce immediate damage to afferent synapses and long-term degeneration of low spontaneous rate auditory nerve fibers. This synaptopathic damage has been shown to correlate with reduced auditory brainstem response (ABR) wave-I amplitudes at suprathreshold levels. The perceptual consequences of this "synaptopathy" remain unknown but have been suggested to include compromised hearing performance in competing background noise. Here, we used a modified startle inhibition paradigm to evaluate whether noise exposures that produce robust TTS and ABR wave-I reduction but not permanent threshold shift (PTS) reduced hearing-in-noise performance. Animals exposed to 109 dB SPL octave band noise showed TTS >30 dB 24-h post noise and modest but persistent ABR wave-I reduction 2 weeks post noise despite full recovery of ABR thresholds. Hearing-in-noise performance was negatively affected by the noise exposure. However, the effect was observed only at the poorest signal to noise ratio and was frequency specific. Although TTS >30 dB 24-h post noise was a predictor of functional deficits, there was no relationship between the degree of ABR wave-I reduction and degree of functional impairment. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Neural representation of the self-heard biosonar click in bottlenose dolphins (Tursiops truncatus).

    PubMed

    Finneran, James J; Mulsow, Jason; Houser, Dorian S; Schlundt, Carolyn E

    2017-05-01

    The neural representation of the dolphin broadband biosonar click was investigated by measuring auditory brainstem responses (ABRs) to "self-heard" clicks masked with noise bursts having various high-pass cutoff frequencies. Narrowband ABRs were obtained by sequentially subtracting responses obtained with noise having lower high-pass cutoff frequencies from those obtained with noise having higher cutoff frequencies. For comparison to the biosonar data, ABRs were also measured in a passive listening experiment, where external clicks and masking noise were presented to the dolphins and narrowband ABRs were again derived using the subtractive high-pass noise technique. The results showed little change in the peak latencies of the ABR to the self-heard click from 28 to 113 kHz; i.e., the high-frequency neural responses to the self-heard click were delayed relative to those of an external, spectrally "pink" click. The neural representation of the self-heard click is thus highly synchronous across the echolocation frequencies and does not strongly resemble that of a frequency modulated downsweep (i.e., decreasing-frequency chirp). Longer ABR latencies at higher frequencies are hypothesized to arise from spectral differences between self-heard clicks and external clicks, forward masking from previously emitted biosonar clicks, or neural inhibition accompanying the emission of clicks.

  15. Neural representation of the self-heard biosonar click in bottlenose dolphins (Tursiops truncatus)

    PubMed Central

    Finneran, James J.; Mulsow, Jason; Houser, Dorian S.; Schlundt, Carolyn E.

    2017-01-01

    The neural representation of the dolphin broadband biosonar click was investigated by measuring auditory brainstem responses (ABRs) to “self-heard” clicks masked with noise bursts having various high-pass cutoff frequencies. Narrowband ABRs were obtained by sequentially subtracting responses obtained with noise having lower high-pass cutoff frequencies from those obtained with noise having higher cutoff frequencies. For comparison to the biosonar data, ABRs were also measured in a passive listening experiment, where external clicks and masking noise were presented to the dolphins and narrowband ABRs were again derived using the subtractive high-pass noise technique. The results showed little change in the peak latencies of the ABR to the self-heard click from 28 to 113 kHz; i.e., the high-frequency neural responses to the self-heard click were delayed relative to those of an external, spectrally “pink” click. The neural representation of the self-heard click is thus highly synchronous across the echolocation frequencies and does not strongly resemble that of a frequency modulated downsweep (i.e., decreasing-frequency chirp). Longer ABR latencies at higher frequencies are hypothesized to arise from spectral differences between self-heard clicks and external clicks, forward masking from previously emitted biosonar clicks, or neural inhibition accompanying the emission of clicks. PMID:28599518

  16. Regulation of the Osem gene by abscisic acid and the transcriptional activator VP1: analysis of cis-acting promoter elements required for regulation by abscisic acid and VP1.

    PubMed

    Hattori, T; Terada, T; Hamasuna, S

    1995-06-01

    Osem, a rice gene homologous to the wheat Em gene, which encodes one of the late-embryogenesis abundant proteins was isolated. The gene was characterized with respect to control of transcription by abscisic acid (ABA) and the transcriptional activator VP1, which is involved in the ABA-regulated gene expression during late embryo-genesis. A fusion gene (Osem-GUS) consisting of the Osem promoter and the bacterial beta-glucuronidase (GUS) gene was constructed and tested in a transient expression system, using protoplasts derived from a suspension-cultured line of rice cells, for activation by ABA and by co-transfection with an expression vector (35S-Osvp1) for the rice VP1 (OSVP1) cDNA. The expression of Osem-GUS was strongly (40- to 150-fold) activated by externally applied ABA and by over-expression of (OS)VP1. The Osem promoter has three ACGTG-containing sequences, motif A, motif B and motif A', which resemble the abscisic acid-responsive element (ABRE) that was previously identified in the wheat Em and the rice Rab16. There is also a CATGCATG sequence, which is known as the Sph box and is shown to be essential for the regulation by VP1 of the maize anthocyanin regulatory gene C1. Focusing on these sequence elements, various mutant derivatives of the Osem promoter in the transient expression system were assayed. The analysis revealed that motif A functions not only as an ABRE but also as a sequence element required for the regulation by (OS)VP1.

  17. Auditory Brainstem Responses for Click and CE-chirp Stimuli in Individuals with and without Occupational Noise Exposure

    PubMed Central

    Pushpalatha, Zeena Venkatacheluvaiah; Konadath, Sreeraj

    2016-01-01

    Introduction: Encoding of CE-chirp and click stimuli in auditory system was studied using auditory brainstem responses (ABRs) among individuals with and without noise exposure. Materials and Methods: The study consisted of two groups. Group 1 (experimental group) consisted of 20 (40 ears) individuals exposed to occupational noise with hearing thresholds within 25 dB HL. They were further divided into three subgroups based on duration of noise exposure (0–5 years of exposure-T1, 5–10 years of exposure-T2, and >10 years of exposure-T3). Group 2 (control group) consisted of 20 individuals (40 ears). Absolute latency and amplitude of waves I, III, and V were compared between the two groups for both click and CE-chirp stimuli. T1, T2, and T3 groups were compared for the same parameters to see the effect of noise exposure duration on CE-chirp and click ABR. Result: In Click ABR, while both the parameters for wave III were significantly poorer for the experimental group, wave V showed a significant decline in terms of amplitude only. There was no significant difference obtained for any of the parameters for wave I. In CE-Chirp ABR, the latencies for all three waves were significantly prolonged in the experimental group. However, there was a significant decrease in terms of amplitude in only wave V for the same group. Discussion: Compared to click evoked ABR, CE-Chirp ABR was found to be more sensitive in comparison of latency parameters in individuals with occupational noise exposure. Monitoring of early pathological changes at the brainstem level can be studied effectively by using CE-Chirp stimulus in comparison to click stimulus. Conclusion: This study indicates that ABR's obtained with CE-chirp stimuli serves as an effective tool to identify the early pathological changes due to occupational noise exposure when compared to click evoked ABR. PMID:27762255

  18. Noise-induced inner hair cell ribbon loss disturbs central arc mobilization: a novel molecular paradigm for understanding tinnitus.

    PubMed

    Singer, Wibke; Zuccotti, Annalisa; Jaumann, Mirko; Lee, Sze Chim; Panford-Walsh, Rama; Xiong, Hao; Zimmermann, Ulrike; Franz, Christoph; Geisler, Hyun-Soon; Köpschall, Iris; Rohbock, Karin; Varakina, Ksenya; Verpoorten, Sandrine; Reinbothe, Thomas; Schimmang, Thomas; Rüttiger, Lukas; Knipper, Marlies

    2013-02-01

    Increasing evidence shows that hearing loss is a risk factor for tinnitus and hyperacusis. Although both often coincide, a causal relationship between tinnitus and hyperacusis has not been shown. Currently, tinnitus and hyperacusis are assumed to be caused by elevated responsiveness in subcortical circuits. We examined both the impact of different degrees of cochlear damage and the influence of stress priming on tinnitus induction. We used (1) a behavioral animal model for tinnitus designed to minimize stress, (2) ribbon synapses in inner hair cells (IHCs) as a measure for deafferentation, (3) the integrity of auditory brainstem responses (ABR) to detect differences in stimulus-evoked neuronal activity, (4) the expression of the activity-regulated cytoskeletal protein, Arc, to identify long-lasting changes in network activity within the basolateral amygdala (BLA), hippocampal CA1, and auditory cortex (AC), and (5) stress priming to investigate the influence of corticosteroid on trauma-induced brain responses. We observed that IHC ribbon loss (deafferentation) leads to tinnitus when ABR functions remain reduced and Arc is not mobilized in the hippocampal CA1 and AC. If, however, ABR waves are functionally restored and Arc is mobilized, tinnitus does not occur. Both central response patterns were found to be independent of a profound threshold loss and could be shifted by the corticosterone level at the time of trauma. We, therefore, discuss the findings in the context of a history of stress that can trigger either an adaptive or nonadaptive brain response following injury.

  19. Expression of CdDHN4, a Novel YSK2-Type Dehydrin Gene from Bermudagrass, Responses to Drought Stress through the ABA-Dependent Signal Pathway

    PubMed Central

    Lv, Aimin; Fan, Nana; Xie, Jianping; Yuan, Shili; An, Yuan; Zhou, Peng

    2017-01-01

    Dehydrin improves plant resistance to many abiotic stresses. In this study, the expression profiles of a dehydrin gene, CdDHN4, were estimated under various stresses and abscisic acid (ABA) treatments in two bermudagrasses (Cynodon dactylon L.): Tifway (drought-tolerant) and C299 (drought-sensitive). The expression of CdDHN4 was up-regulated by high temperatures, low temperatures, drought, salt and ABA. The sensitivity of CdDHN4 to ABA and the expression of CdDHN4 under drought conditions were higher in Tifway than in C299. A 1239-bp fragment, CdDHN4-P, the partial upstream sequence of the CdDHN4 gene, was cloned by genomic walking from Tifway. Bioinformatic analysis showed that the CdDHN4-P sequence possessed features typical of a plant promoter and contained many typical cis elements, including a transcription initiation site, a TATA-box, an ABRE, an MBS, a MYC, an LTRE, a TATC-box and a GT1-motif. Transient expression in tobacco leaves demonstrated that the promoter CdDHN4-P can be activated by ABA, drought and cold. These results indicate that CdDHN4 is regulated by an ABA-dependent signal pathway and that the high sensitivity of CdDHN4 to ABA might be an important mechanism enhancing the drought tolerance of bermudagrass. PMID:28559903

  20. Identification of conserved drought stress responsive gene-network across tissues and developmental stages in rice.

    PubMed

    Smita, Shuchi; Katiyar, Amit; Pandey, Dev Mani; Chinnusamy, Viswanathan; Archak, Sunil; Bansal, Kailash Chander

    2013-01-01

    Identification of genes that are coexpressed across various tissues and environmental stresses is biologically interesting, since they may play coordinated role in similar biological processes. Genes with correlated expression patterns can be best identified by using coexpression network analysis of transcriptome data. In the present study, we analyzed the temporal-spatial coordination of gene expression in root, leaf and panicle of rice under drought stress and constructed network using WGCNA and Cytoscape. Total of 2199 differentially expressed genes (DEGs) were identified in at least three or more tissues, wherein 88 genes have coordinated expression profile among all the six tissues under drought stress. These 88 highly coordinated genes were further subjected to module identification in the coexpression network. Based on chief topological properties we identified 18 hub genes such as ABC transporter, ATP-binding protein, dehydrin, protein phosphatase 2C, LTPL153 - Protease inhibitor, phosphatidylethanolaminebinding protein, lactose permease-related, NADP-dependent malic enzyme, etc. Motif enrichment analysis showed the presence of ABRE cis-elements in the promoters of > 62% of the coordinately expressed genes. Our results suggest that drought stress mediated upregulated gene expression was coordinated through an ABA-dependent signaling pathway across tissues, at least for the subset of genes identified in this study, while down regulation appears to be regulated by tissue specific pathways in rice.

  1. Expression of CdDHN4, a Novel YSK2-Type Dehydrin Gene from Bermudagrass, Responses to Drought Stress through the ABA-Dependent Signal Pathway.

    PubMed

    Lv, Aimin; Fan, Nana; Xie, Jianping; Yuan, Shili; An, Yuan; Zhou, Peng

    2017-01-01

    Dehydrin improves plant resistance to many abiotic stresses. In this study, the expression profiles of a dehydrin gene, CdDHN4 , were estimated under various stresses and abscisic acid (ABA) treatments in two bermudagrasses ( Cynodon dactylon L.): Tifway (drought-tolerant) and C299 (drought-sensitive). The expression of CdDHN4 was up-regulated by high temperatures, low temperatures, drought, salt and ABA. The sensitivity of CdDHN4 to ABA and the expression of CdDHN4 under drought conditions were higher in Tifway than in C299. A 1239-bp fragment, CdDHN4-P, the partial upstream sequence of the CdDHN4 gene, was cloned by genomic walking from Tifway. Bioinformatic analysis showed that the CdDHN4-P sequence possessed features typical of a plant promoter and contained many typical cis elements, including a transcription initiation site, a TATA-box, an ABRE, an MBS, a MYC, an LTRE, a TATC-box and a GT1-motif. Transient expression in tobacco leaves demonstrated that the promoter CdDHN4-P can be activated by ABA, drought and cold. These results indicate that CdDHN4 is regulated by an ABA-dependent signal pathway and that the high sensitivity of CdDHN4 to ABA might be an important mechanism enhancing the drought tolerance of bermudagrass.

  2. Comparison between ABR with click and narrow band chirp stimuli in children.

    PubMed

    Zirn, Stefan; Louza, Julia; Reiman, Viktor; Wittlinger, Natalie; Hempel, John-Martin; Schuster, Maria

    2014-08-01

    Click and chirp-evoked auditory brainstem responses (ABR) are applied for the estimation of hearing thresholds in children. The present study analyzes ABR thresholds across a large sample of children's ears obtained with both methods. The aim was to demonstrate the correlation between both methods using narrow band chirp and click stimuli. Click and chirp evoked ABRs were measured in 253 children aged from 0 to 18 years to determine their individual auditory threshold. The delay-compensated stimuli were narrow band CE chirps with either 2000 Hz or 4000 Hz center frequencies. Measurements were performed consecutively during natural sleep, and under sedation or general anesthesia. Threshold estimation was performed for each measurement by two experienced audiologists. Pearson-correlation analysis revealed highly significant correlations (r=0.94) between click and chirp derived thresholds for both 2 kHz and 4 kHz chirps. No considerable differences were observed either between different age ranges or gender. Comparing the thresholds estimated using ABR with click stimuli and chirp stimuli, only 0.8-2% for the 2000 Hz NB-chirp and 0.4-1.2% of the 4000 Hz NB-chirp measurements differed more than 15 dB for different degrees of hearing loss or normal hearing. The results suggest that either NB-chirp or click ABR is sufficient for threshold estimation. This holds for the chirp frequencies of 2000 Hz and 4000 Hz. The use of either click- or chirp-evoked ABR allows a reduction of recording time in young infants. Nevertheless, to cross-check the results of one of the methods, we recommend measurements with the other method as well. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Differential responses to acoustic damage and furosemide in auditory brainstem and otoacoustic emission measures

    NASA Astrophysics Data System (ADS)

    Mills, David M.

    2003-02-01

    Characteristics of distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs) were measured in Mongolian gerbil before and after the introduction of two different auditory dysfunctions: (1) acoustic damage with a high-intensity tone, or (2) furosemide intoxication. The goal was to find emission parameters and measures that best differentiated between the two dysfunctions, e.g., at a given ABR threshold elevation. Emission input-output or ``growth'' functions were used (frequencies f1 and f2, f2/f1=1.21) with equal levels, L1=L2, and unequal levels, with L1=L2+20 dB. The best parametric choice was found to be unequal stimulus levels, and the best measure was found to be the change in the emission threshold level, Δx. The emission threshold was defined as the stimulus level required to reach a criterion emission amplitude, in this case -10 dB SPL. (The next best measure was the change in emission amplitude at high stimulus levels, specifically that measured at L1×L2=90×70 dB SPL.) For an ABR threshold shift of 20 dB or more, there was essentially no overlap in the emission threshold measures for the two conditions, sound damage or furosemide. The dividing line between the two distributions increased slowly with the change in ABR threshold, ΔABR, and was given by Δxt=0.6 ΔABR+8 dB. For a given ΔABR, if the shift in emission threshold was more than the calculated dividing line value, Δxt, the auditory dysfunction was due to acoustic damage, if less, it was due to furosemide.

  4. Threshold changes of ABR results in toddlers and children.

    PubMed

    Louza, Julia; Polterauer, Daniel; Wittlinger, Natalie; Muzaini, Hanan Al; Scheckinger, Siiri; Hempel, Martin; Schuster, Maria

    2016-06-01

    Auditory brainstem response (ABR) is a clinically established method to identify the hearing threshold in young children and is regularly performed after hearing screening has failed. Some studies have shown that, after the first diagnosis of hearing impairment in ABR, further development takes place in a spectrum between progression of hearing loss and, surprisingly, hearing improvement. The aim of this study is to evaluate changes over time of auditory thresholds measured by ABR among young children. For this retrospective study, 459 auditory brainstem measurements were performed and analyzed between 2010 and 2014. Hearing loss was detected and assessed according to national guidelines. 104 right ears and 101 left ears of 116 children aged between 0 and 3 years with multiple ABR measurements were included. The auditory threshold was identified using click and/or NB-chirp-stimuli in natural sleep or in general anesthesia. The frequency of differences of at least more than 10dB between the measurements was identified. In 37 (35%) measurements of right ears and 38 (38%) of left ears there was an improvement of the auditory threshold of more than 10dB; in 27 of those measurements more than 20dB improvement was found. Deterioration was seen in 12% of the right ears and 10% of the left ears. Only half of the children had stable hearing thresholds in repeated measurements. The time between the measurements was on average 5 months (0 to 31 months). Hearing threshold changes are often seen in repeated ABR measurements. Therefore multiple measurements are necessary when ABR yields abnormal. Hearing threshold changes should be taken into account for hearing aid provision. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Auditory brainstem response to complex sounds predicts self-reported speech-in-noise performance.

    PubMed

    Anderson, Samira; Parbery-Clark, Alexandra; White-Schwoch, Travis; Kraus, Nina

    2013-02-01

    To compare the ability of the auditory brainstem response to complex sounds (cABR) to predict subjective ratings of speech understanding in noise on the Speech, Spatial, and Qualities of Hearing Scale (SSQ; Gatehouse & Noble, 2004) relative to the predictive ability of the Quick Speech-in-Noise test (QuickSIN; Killion, Niquette, Gudmundsen, Revit, & Banerjee, 2004) and pure-tone hearing thresholds. Participants included 111 middle- to older-age adults (range = 45-78) with audiometric configurations ranging from normal hearing levels to moderate sensorineural hearing loss. In addition to using audiometric testing, the authors also used such evaluation measures as the QuickSIN, the SSQ, and the cABR. Multiple linear regression analysis indicated that the inclusion of brainstem variables in a model with QuickSIN, hearing thresholds, and age accounted for 30% of the variance in the Speech subtest of the SSQ, compared with significantly less variance (19%) when brainstem variables were not included. The authors' results demonstrate the cABR's efficacy for predicting self-reported speech-in-noise perception difficulties. The fact that the cABR predicts more variance in self-reported speech-in-noise (SIN) perception than either the QuickSIN or hearing thresholds indicates that the cABR provides additional insight into an individual's ability to hear in background noise. In addition, the findings underscore the link between the cABR and hearing in noise.

  6. Identification, occurrence, and validation of DRE and ABRE Cis-regulatory motifs in the promoter regions of genes of Arabidopsis thaliana.

    PubMed

    Mishra, Sonal; Shukla, Aparna; Upadhyay, Swati; Sanchita; Sharma, Pooja; Singh, Seema; Phukan, Ujjal J; Meena, Abha; Khan, Feroz; Tripathi, Vineeta; Shukla, Rakesh Kumar; Shrama, Ashok

    2014-04-01

    Plants posses a complex co-regulatory network which helps them to elicit a response under diverse adverse conditions. We used an in silico approach to identify the genes with both DRE and ABRE motifs in their promoter regions in Arabidopsis thaliana. Our results showed that Arabidopsis contains a set of 2,052 genes with ABRE and DRE motifs in their promoter regions. Approximately 72% or more of the total predicted 2,052 genes had a gap distance of less than 400 bp between DRE and ABRE motifs. For positional orientation of the DRE and ABRE motifs, we found that the DR form (one in direct and the other one in reverse orientation) was more prevalent than other forms. These predicted 2,052 genes include 155 transcription factors. Using microarray data from The Arabidopsis Information Resource (TAIR) database, we present 44 transcription factors out of 155 which are upregulated by more than twofold in response to osmotic stress and ABA treatment. Fifty-one transcripts from the one predicted above were validated using semiquantitative expression analysis to support the microarray data in TAIR. Taken together, we report a set of genes containing both DRE and ABRE motifs in their promoter regions in A. thaliana, which can be useful to understand the role of ABA under osmotic stress condition. © 2013 Institute of Botany, Chinese Academy of Sciences.

  7. Aging effects on the Binaural Interaction Component of the Auditory Brainstem Response in the Mongolian Gerbil: Effects of Interaural Time and Level Differences

    PubMed Central

    Laumen, Geneviève; Tollin, Daniel J.; Beutelmann, Rainer; Klump, Georg M.

    2016-01-01

    The effect of interaural time difference (ITD) and interaural level difference (ILD) on wave 4 of the binaural and summed monaural auditory brainstem responses (ABRs) as well as on the DN1 component of the binaural interaction component (BIC) of the ABR in young and old Mongolian gerbils (Meriones unguiculatus) was investigated. Measurements were made at a fixed sound pressure level (SPL) and a fixed level above visually detected ABR threshold to compensate for individual hearing threshold differences. In both stimulation modes (fixed SPL and fixed level above visually detected ABR threshold) an effect of ITD on the latency and the amplitude of wave 4 as well as of the BIC was observed. With increasing absolute ITD values BIC latencies were increased and amplitudes were decreased. ILD had a much smaller effect on these measures. Old animals showed a reduced amplitude of the DN1 component. This difference was due to a smaller wave 4 in the summed monaural ABRs of old animals compared to young animals whereas wave 4 in the binaural-evoked ABR showed no age-related difference. In old animals the small amplitude of the DN1 component was correlated with small binaural-evoked wave 1 and wave 3 amplitudes. This suggests that the reduced peripheral input affects central binaural processing which is reflected in the BIC. PMID:27173973

  8. Abr1, a Transposon-Like Element in the Genome of the Cultivated Mushroom Agaricus bisporus (Lange) Imbach

    PubMed Central

    Sonnenberg, Anton S. M.; Baars, Johan J. P.; Mikosch, Thomas S. P.; Schaap, Peter J.; Van Griensven, Leo J. L. D.

    1999-01-01

    A 300-bp repetitive element was found in the genome of the white button mushroom, Agaricus bisporus, and designated Abr1. It is present in ∼15 copies per haploid genome in the commercial strain Horst U1. Analysis of seven copies showed 89 to 97% sequence identity. The repeat has features typical of class II transposons (i.e., terminal inverted repeats, subterminal repeats, and a target site duplication of 7 bp). The latter shows a consensus sequence. When used as probe on Southern blots, Abr1 identifies relatively little variation within traditional and present-day commercial strains, indicating that most strains are identical or have a common origin. In contrast to these cultivars, high variation is found among field-collected strains. Furthermore, a remarkable difference in copy numbers of Abr1 was found between A. bisporus isolates with a secondarily homothallic life cycle and those with a heterothallic life cycle. Abr1 is a type II transposon not previously reported in basidiomycetes and appears to be useful for the identification of strains within the species A. bisporus. PMID:10427018

  9. Efficacy of Distortion Product Oto-Acoustic Emission (OAE)/Auditory Brainstem Evoked Response (ABR) Protocols in Universal Neonatal Hearing Screening and Detecting Hearing Loss in Children <2 Years of Age.

    PubMed

    Mishra, Girish; Sharma, Yojana; Mehta, Kanishk; Patel, Gunjan

    2013-04-01

    Deafness is commonest curable childhood handicap. Most remedies and programmes don't address this issue at childhood level leading to detrimental impact on development of newborns. Aims and objectives are (A) screen all newborns for deafness and detect prevalence of deafness in children less than 2 years of age. and (B) assess efficacy of multi-staged OAE/ABR protocol for hearing screening. Non-randomized, prospective study from August 2008 to August 2011. All infants underwent a series of oto-acoustic emission (OAE) and final confirmatory auditory brainstem evoked response (ABR) audiometry. Finally, out of 1,101 children, 1,069 children passed the test while 12 children had impaired hearing after final testing, confirmed by ABR. Positive predictive value of OAE after multiple test increased to 100 %. OAE-ABR test series is effective in screening neonates and multiple tests reduce economic burden. High risk screening will miss nearly 50 % deaf children, thus universal screening is indispensable in picking early deafness.

  10. Economic evaluation of long-term impacts of universal newborn hearing screening.

    PubMed

    Chiou, Shu-Ti; Lung, Hou-Ling; Chen, Li-Sheng; Yen, Amy Ming-Fang; Fann, Jean Ching-Yuan; Chiu, Sherry Yueh-Hsia; Chen, Hsiu-Hsi

    2017-01-01

    Little is known about the long-term efficacious and economic impacts of universal newborn hearing screening (UNHS). An analytical Markov decision model was framed with two screening strategies: UNHS with transient evoked otoacoustic emission (TEOAE) test and automatic acoustic brainstem response (aABR) test against no screening. By estimating intervention and long-term costs on treatment and productivity losses and the utility of life years determined by the status of hearing loss, we computed base-case estimates of the incremental cost-utility ratios (ICURs). The scattered plot of ICUR and acceptability curve was used to assess the economic results of aABR versus TEOAE or both versus no screening. A hypothetical cohort of 200,000 Taiwanese newborns. TEOAE and aABR dominated over no screening strategy (ICUR = $-4800.89 and $-4111.23, indicating less cost and more utility). Given $20,000 of willingness to pay (WTP), the probability of being cost-effective of aABR against TEOAE was up to 90%. UNHS for hearing loss with aABR is the most economic option and supported by economically evidence-based evaluation from societal perspective.

  11. Fermentative hydrogen production from soybean protein processing wastewater in an anaerobic baffled reactor (ABR) using anaerobic mixed consortia.

    PubMed

    Zhu, Ge-fu; Li, Jian-zheng; Liu, Chao-xiang

    2012-09-01

    Fermentative H(2) production from soybean protein processing wastewater (SPPW) was investigated in a four-compartment anaerobic baffled reactor (ABR) using anaerobic mixed cultures under continuous flow condition in the present study. After being inoculated with aerobic activated sludge and operated at the inoculants of 5.98 gVSS L(-1), COD of 5000 mg L(-1), HRT of 16 h and temperature of (35 ± 1) °C for 22 days, the ABR achieved stable ethanol-type fermentation. The specific hydrogen production rate of anaerobic activated sludge was 165 LH(2)kg MLVSS(-1) day(-1), the substrate conversion rate was 600.83 LH(2)kg COD(-1)and the COD removal efficiency was 44.73% at the stable operation status. The ABR system exhibited a better stability and higher hydrogen yields than continuous stirring tank reactor under the same operational condition. The experimental data documented the feasibility of substrate degradation along with molecular H(2) generation utilizing SPPW as primary carbon source in the ABR system.

  12. Auditory brainstem response in neonates: influence of gender and weight/gestational age ratio

    PubMed Central

    Angrisani, Rosanna M. Giaffredo; Bautzer, Ana Paula D.; Matas, Carla Gentile; de Azevedo, Marisa Frasson

    2013-01-01

    OBJECTIVE: To investigate the influence of gender and weight/gestational age ratio on the Auditory Brainstem Response (ABR) in preterm (PT) and term (T) newborns. METHODS: 176 newborns were evaluated by ABR; 88 were preterm infants - 44 females (22 small and 22 appropriate for gestational age) and 44 males (22 small and 22 appropriate for gestational age). The preterm infants were compared to 88 term infants - 44 females (22 small and 22 appropriate for gestational age) and 44 males (22 small and 22 appropriate for gestational age). All newborns had bilateral presence of transient otoacoustic emissions and type A tympanometry. RESULTS: No interaural differences were found. ABR response did not differentiate newborns regarding weight/gestational age in males and females. Term newborn females showed statistically shorter absolute latencies (except on wave I) than males. This finding did not occur in preterm infants, who had longer latencies than term newborns, regardless of gender. CONCLUSIONS: Gender and gestational age influence term infants' ABR, with lower responses in females. The weight/gestational age ratio did not influence ABR response in either groups. PMID:24473955

  13. IGF-1 deficiency causes atrophic changes associated with upregulation of VGluT1 and downregulation of MEF2 transcription factors in the mouse cochlear nuclei.

    PubMed

    Fuentes-Santamaría, V; Alvarado, J C; Rodríguez-de la Rosa, L; Murillo-Cuesta, S; Contreras, J; Juiz, J M; Varela-Nieto, I

    2016-03-01

    Insulin-like growth factor 1 (IGF-1) is a neurotrophic protein that plays a crucial role in modulating neuronal function and synaptic plasticity in the adult brain. Mice lacking the Igf1 gene exhibit profound deafness and multiple anomalies in the inner ear and spiral ganglion. An issue that remains unknown is whether, in addition to these peripheral abnormalities, IGF-1 deficiency also results in structural changes along the central auditory pathway that may contribute to an imbalance between excitation and inhibition, which might be reflected in abnormal auditory brainstem responses (ABR). To assess such a possibility, we evaluated the morphological and physiological alterations in the cochlear nucleus complex of the adult mouse. The expression and distribution of the vesicular glutamate transporter 1 (VGluT1) and the vesicular inhibitory transporter (VGAT), which were used as specific markers for labeling excitatory and inhibitory terminals, and the involvement of the activity-dependent myocyte enhancer factor 2 (MEF2) transcription factors in regulating excitatory synapses were assessed in a 4-month-old mouse model of IGF-1 deficiency and neurosensorial deafness (Igf1 (-/-) homozygous null mice). The results demonstrate decreases in the cochlear nucleus area and cell size along with cell loss in the cochlear nuclei of the deficient mouse. Additionally, our results demonstrate that there is upregulation of VGluT1, but not VGAT, immunostaining and downregulation of MEF2 transcription factors together with increased wave II amplitude in the ABR recording. Our observations provide evidence of an abnormal neuronal cytoarchitecture in the cochlear nuclei of Igf1 (-/-) null mice and suggest that the increased efficacy of glutamatergic synapses might be mediated by MEF2 transcription factors.

  14. Universal effect of dynamical reinforcement learning mechanism in spatial evolutionary games

    NASA Astrophysics Data System (ADS)

    Zhang, Hai-Feng; Wu, Zhi-Xi; Wang, Bing-Hong

    2012-06-01

    One of the prototypical mechanisms in understanding the ubiquitous cooperation in social dilemma situations is the win-stay, lose-shift rule. In this work, a generalized win-stay, lose-shift learning model—a reinforcement learning model with dynamic aspiration level—is proposed to describe how humans adapt their social behaviors based on their social experiences. In the model, the players incorporate the information of the outcomes in previous rounds with time-dependent aspiration payoffs to regulate the probability of choosing cooperation. By investigating such a reinforcement learning rule in the spatial prisoner's dilemma game and public goods game, a most noteworthy viewpoint is that moderate greediness (i.e. moderate aspiration level) favors best the development and organization of collective cooperation. The generality of this observation is tested against different regulation strengths and different types of network of interaction as well. We also make comparisons with two recently proposed models to highlight the importance of the mechanism of adaptive aspiration level in supporting cooperation in structured populations.

  15. The erosion and abrasion-inhibiting effect of TiF(4) and NaF varnishes and solutions on enamel in vitro.

    PubMed

    Levy, Flávia Mauad; Magalhães, Ana Carolina; Gomes, Marina Franciscon; Comar, Livia Picchi; Rios, Daniela; Buzalaf, Marília Afonso Rabelo

    2012-01-01

    OBJECTIVE. Previous in vitro study has shown that TiF(4) varnish might reduce enamel erosion. No data regarding the effect of this experimental varnish on enamel erosion plus abrasion, however, are available so far. Thus, this in vitro study aimed to analyse the effect of TiF(4) compared with NaF varnishes and solutions, to protect against enamel erosion with or without abrasion. METHODS. Enamel specimens were pre-treated with experimental-TiF(4) (2.45% F), experimental-NaF (2.45% F), NaF-Duraphat (2.26% F), and placebo varnishes; NaF (2.26% F) and TiF(4) (2.45% F) solutions. Controls remained untreated. The erosive challenge was performed using a soft drink (pH 2.6) 4 × 90 s/day (ERO) and the toothbrushing abrasion (ERO+ABR) 2 × 10 s/day, for 5 days. Between the challenges, the specimens were exposed to artificial saliva. Enamel loss was measured profilometrically (μm). RESULTS. Kruskal-Wallis/Dunn tests showed that all fluoridated varnishes (TiF(4) -ERO:0.53 ± 0.20, ERO+ABR:0.65 ± 0.19/NaF-ERO:0.94 ± 0.18, ERO+ABR:1.74 ± 0.37/Duraphat-ERO:1.00 ± 0.37, ERO+ABR:1.72 ± 0.58) were able to significantly reduce enamel loss when compared with placebo varnish (ERO:3.45 ± 0.41/ERO+ABR:3.20 ± 0.66) (P < 0.0001). Placebo varnish, control (ERO:2.68 ± 0.53/ERO+ABR:3.01 ± 0.34), and fluoridated (NaF-ERO:2.84 ± 0.09/ERO+ABR:2.40 ± 0.21/TiF(4) -ERO:3.55 ± 0.59/ERO+ABR:4.10 ± 0.38) solutions did not significantly differ from each other. CONCLUSION. Based on the results, it can be concluded that the TiF(4) varnish seems to be a promising treatment to reduce enamel loss under mild erosive and abrasive conditions in vitro. © 2011 The Authors. International Journal of Paediatric Dentistry © 2011 BSPD, IAPD and Blackwell Publishing Ltd.

  16. 7 CFR 4279.137 - Financial statements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE GUARANTEED LOANMAKING Business and Industry Loans... connection with loans that depend heavily on inventory and accounts receivable for collateral. ...

  17. 7 CFR 4279.137 - Financial statements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE GUARANTEED LOANMAKING Business and Industry Loans... connection with loans that depend heavily on inventory and accounts receivable for collateral. ...

  18. 7 CFR 4279.137 - Financial statements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE GUARANTEED LOANMAKING Business and Industry Loans... connection with loans that depend heavily on inventory and accounts receivable for collateral. ...

  19. 7 CFR 4279.137 - Financial statements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE GUARANTEED LOANMAKING Business and Industry Loans... connection with loans that depend heavily on inventory and accounts receivable for collateral. ...

  20. Using game theory to analyze green stormwater infrastructure implementation policies

    NASA Astrophysics Data System (ADS)

    William, R. K.; Garg, J.; Stillwell, A. S.

    2017-12-01

    While green stormwater infrastructure is a useful approach in addressing multiple challenges facing the urban environment, little consensus exists on how to best incentivize its adoption by private landowners. Game theory, a field of study designed to model conflict and cooperation between two or more agents, is well-suited to address this policy question. We used a cooperative game theory framework to analyze the impacts of three different policy approaches frequently used to incentivize the uptake of green infrastructure by private landowners: municipal regulation, direct grants, and stormwater fees. The results indicate that municipal regulation leads to the greatest environmental benefits; however, the choice of "best" regulatory approach is dependent on a variety of different factors including political and financial considerations. Policy impacts are also highly dependent on agents' spatial positions within the stormwater network. This finding leads to important questions of social equity and environmental justice.

  1. Dormancy-Associated MADS-Box (DAM) and the Abscisic Acid Pathway Regulate Pear Endodormancy Through a Feedback Mechanism.

    PubMed

    Tuan, Pham Anh; Bai, Songling; Saito, Takanori; Ito, Akiko; Moriguchi, Takaya

    2017-08-01

    In the pear 'Kosui' (Pyrus pyrifolia Nakai), the dormancy-associated MADS-box (PpDAM1 = PpMADS13-1) gene has been reported to play an essential role in bud endodormancy. Here, we found that PpDAM1 up-regulated expression of 9-cis-epoxycarotenoid dioxygenase (PpNCED3), which is a rate-limiting gene for ABA biosynthesis. Transient assays with a dual luciferase reporter system (LUC assay) and electrophoretic mobility shift assay (EMSA) showed that PpDAM1 activated PpNCED3 expression by binding to the CArG motif in the PpNCED3 promoter. PpNCED3 expression was increased toward endodormancy release in lateral flower buds of 'Kosui', which is consistent with the induced levels of ABA, its catabolism (ABA 8'-hydroxylase) and signaling genes (type 2C protein phosphatase genes and SNF1-related protein kinase 2 genes). In addition, we found that an ABA response element (ABRE)-binding transcription factor, PpAREB1, exhibiting high expression concomitant with endodormancy release, bound to three ABRE motifs in the promoter region of PpDAM1 and negatively regulated its activity. Taken together, our results suggested a feedback regulation between PpDAM1 and the ABA metabolism and signaling pathway during endodormancy of pear. This first evidence of an interaction between a DAM and ABA biosynthesis in vitro will provide further insights into bud endodormancy regulatory mechanisms of deciduous trees including pear. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Kruppel-like Factor 9 is a Negative Regulator of Ligand-dependent Estrogen Receptor Alpha Signaling in Ishikawa Endometrial Adenocarcinoma Cells

    USDA-ARS?s Scientific Manuscript database

    Estrogen (E) and progesterone (P), acting through their respective receptors and other nuclear proteins, exhibit opposing activities in target cells. We previously reported that Krüppel-like factor 9 (KLF9) cooperates with progesterone receptor (PR) to facilitate P-dependent gene transcription in ut...

  3. 78 FR 27470 - Projects Approved for Consumptive Uses of Water

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-10

    .... 4. Carrizo Marcellus, LLC, Pad ID: Baumunk Lake South, ABR- 201303004, Fox Township, Sullivan County..., Pad ID: Baumunk Lake North, ABR- 201303005, Fox Township, Sullivan County, Pa.; Consumptive Use of Up...

  4. Speech-evoked auditory brainstem responses in children with hearing loss.

    PubMed

    Koravand, Amineh; Al Osman, Rida; Rivest, Véronique; Poulin, Catherine

    2017-08-01

    The main objective of the present study was to investigate subcortical auditory processing in children with sensorineural hearing loss. Auditory Brainstem Responses (ABRs) were recorded using click and speech/da/stimuli. Twenty-five children, aged 6-14 years old, participated in the study: 13 with normal hearing acuity and 12 with sensorineural hearing loss. No significant differences were observed for the click-evoked ABRs between normal hearing and hearing-impaired groups. For the speech-evoked ABRs, no significant differences were found for the latencies of the following responses between the two groups: onset (V and A), transition (C), one of the steady-state wave (F), and offset (O). However, the latency of the steady-state waves (D and E) was significantly longer for the hearing-impaired compared to the normal hearing group. Furthermore, the amplitude of the offset wave O and of the envelope frequency response (EFR) of the speech-evoked ABRs was significantly larger for the hearing-impaired compared to the normal hearing group. Results obtained from the speech-evoked ABRs suggest that children with a mild to moderately-severe sensorineural hearing loss have a specific pattern of subcortical auditory processing. Our results show differences for the speech-evoked ABRs in normal hearing children compared to hearing-impaired children. These results add to the body of the literature on how children with hearing loss process speech at the brainstem level. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Effect of Daily Supine LBNP Exercise on Gastrointestinal Motility During Antiorthostatic Bedrest in Normal Subjects

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi; DeKerlegand, D.; Hargens, Alan R. (Technical Monitor)

    1997-01-01

    Space flight alters gastrointestinal (GI) function in general, and GI motility, in particular. This can decrease appetite, affect the body's ability to absorb nutrients, fluids and electrolytes, and contribute to a negative energy balance. Antiorthostatic bed rest (ABR) has been used to simulate microgravity-induced physiological changes in human subjects. The objective of this investigation is to determine if daily supine lower body negative pressure (LBNP) exercise will maintain GI motility at near normal levels during ABR. Eight subjects participated in the study protocol consisting of an ambulatory phase scheduled before bedrest periods and two 14 day bed rest (6 deg head-down tilt) periods, once with and another time without exercise. Supine treadmill running in an LBNP chamber was used for exercise. Mouth-to-cecum transit time (MCTT) of lactulose was measured indirectly using the rise in breath hydrogen level after oral administration of lactulose (20 g) following a standard low-fiber breakfast. GI motility during ambulatory and ABR periods was assessed using MCTT data. Results of this Study indicate that GI motility during ABR without exercise decreased by 45% [MCTT +/- S.E.M. 56.2 +/- 6.0 (Ambulatory); 87.3 +/- 8.3 (ABR)]. Supine LBNP exercise did not significantly alter this reduction in GI motility during ABR [MCTT +/- S.E.M. 81.3 +/- 4.2 (Exercise); 87.3 +/- 8.3 (No Exercise)]. These results suggest that supine LBNP exercise may not be an effective countermeasure for microgravity-induced decrements in GI motility and function.

  6. Pharmacokinetics of Intranasal Scopolamine Gel Formation During Antiorthostatic Bedrest - A Microgravity Analog

    NASA Technical Reports Server (NTRS)

    Lakshmi, Putcha; Singh, R. P.; Crady, V. A.; Derendorf, H.

    2011-01-01

    Space Motion sickness (SMS) is an age old problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is the most frequently used drug for the treatment of motion sickness (MS) which is currently available in transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability thus allowing precise and reduced dosing options in addition to offering rescue and treatment options. As such, an intranasal gel dosage formulation of scopolamine (INSCOP) was developed and Pharmacokinetics (PK) and bioavailability were determined under IND guidelines. The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostatic bedrest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 and 0.4 mg doses of INSCOP during AMB and ABR in a four-way crossover design. Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose. Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration versus time curve (AUC) during ABR after the 0.4 mg dose. This difference in AUC and Cls at the higher but not the lower dose during ABR may suggest that ABR may affect metabolism and/or clearance at higher doses of INSCOP. These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.

  7. Antibiotic Resistance in the Food Chain: A Developing Country-Perspective

    PubMed Central

    Founou, Luria Leslie; Founou, Raspail Carrel; Essack, Sabiha Yusuf

    2016-01-01

    Antibiotics are now “endangered species” facing extinction due to the worldwide emergence of antibiotic resistance (ABR). Food animals are considered as key reservoirs of antibiotic-resistant bacteria with the use of antibiotics in the food production industry having contributed to the actual global challenge of ABR. There are no geographic boundaries to impede the worldwide spread of ABR. If preventive and containment measures are not applied locally, nationally and regionally, the limited interventions in one country, continent and for instance, in the developing world, could compromise the efficacy and endanger ABR containment policies implemented in other parts of the world, the best-managed high-resource countries included. Multifaceted, comprehensive, and integrated measures complying with the One Health approach are imperative to ensure food safety and security, effectively combat infectious diseases, curb the emergence and spread of ABR, and preserve the efficacy of antibiotics for future generations. Countries should follow the World Health Organization, World Organization for Animal Health, and the Food and Agriculture Organization of the United Nations recommendations to implement national action plans encompassing human, (food) animal, and environmental sectors to improve policies, interventions and activities that address the prevention and containment of ABR from farm-to-fork. This review covers (i) the origin of antibiotic resistance, (ii) pathways by which bacteria spread to humans from farm-to-fork, (iii) differences in levels of antibiotic resistance between developed and developing countries, and (iv) prevention and containment measures of antibiotic resistance in the food chain. PMID:27933044

  8. Neonate Auditory Brainstem Responses to CE-Chirp and CE-Chirp Octave Band Stimuli I: Versus Click and Tone Burst Stimuli.

    PubMed

    Cobb, Kensi M; Stuart, Andrew

    The purpose of the study was to generate normative auditory brainstem response (ABR) wave component peak latency and amplitude values for neonates with air- and bone-conducted CE-Chirps and air-conducted CE-Chirp octave band stimuli (i.e., 500, 1000, 2000, and 4000 Hz). A second objective was to compare neonate ABRs to CE-Chirp stimuli with ABR responses to traditional click and tone burst stimuli with the same stimulus parameters. Participants were 168 healthy neonates. ABRs were obtained to air- and bone-conducted CE-Chirp and click stimuli and air-conducted CE-Chirp octave band and tone burst stimuli. The effects of stimulus level, rate, and polarity were examined with air-conducted CE-Chirps and clicks. The effect of stimulus level was also examined with bone-conducted CE-Chirps and clicks and air-conducted CE-Chirp octave band stimuli. In general, ABR wave V amplitudes to air- and bone-conducted CE-Chirp stimuli were significantly larger (p < 0.05) than those evoked to traditional click and tone burst stimuli. Systematic statistically significant (p < 0.05) wave V latency differences existed between the air- and bone-conducted CE-Chirp and CE-Chirp octave band stimuli relative to traditional click and tone burst stimuli. ABRs to air- and bone-conducted CE-Chirps and CE-Chirp octave band stimuli may be valuable in the assessment of newborn infants. However, the prognostic value of such stimuli needs to be validated.

  9. Aging effects on the binaural interaction component of the auditory brainstem response in the Mongolian gerbil: Effects of interaural time and level differences.

    PubMed

    Laumen, Geneviève; Tollin, Daniel J; Beutelmann, Rainer; Klump, Georg M

    2016-07-01

    The effect of interaural time difference (ITD) and interaural level difference (ILD) on wave 4 of the binaural and summed monaural auditory brainstem responses (ABRs) as well as on the DN1 component of the binaural interaction component (BIC) of the ABR in young and old Mongolian gerbils (Meriones unguiculatus) was investigated. Measurements were made at a fixed sound pressure level (SPL) and a fixed level above visually detected ABR threshold to compensate for individual hearing threshold differences. In both stimulation modes (fixed SPL and fixed level above visually detected ABR threshold) an effect of ITD on the latency and the amplitude of wave 4 as well as of the BIC was observed. With increasing absolute ITD values BIC latencies were increased and amplitudes were decreased. ILD had a much smaller effect on these measures. Old animals showed a reduced amplitude of the DN1 component. This difference was due to a smaller wave 4 in the summed monaural ABRs of old animals compared to young animals whereas wave 4 in the binaural-evoked ABR showed no age-related difference. In old animals the small amplitude of the DN1 component was correlated with small binaural-evoked wave 1 and wave 3 amplitudes. This suggests that the reduced peripheral input affects central binaural processing which is reflected in the BIC. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Auditory brainstem response (ABR) profiling tests as diagnostic support for schizophrenia and adult attention-deficit hyperactivity disorder (ADHD).

    PubMed

    Juselius Baghdassarian, Eva; Nilsson Markhed, Maria; Lindström, Eva; Nilsson, Björn M; Lewander, Tommy

    2018-06-01

    To evaluate the performances of two auditory brainstem response (ABR) profiling tests as potential biomarkers and diagnostic support for schizophrenia and adult attention-deficit hyperactivity disorder (ADHD), respectively, in an investigator-initiated blinded study design. Male and female patients with schizophrenia (n=26) and adult ADHD (n=24) meeting Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM IV) diagnostic criteria and healthy controls (n=58) comprised the analysis set (n=108) of the total number of study participants (n=119). Coded sets of randomized ABR recordings were analysed by an independent party blinded to clinical diagnoses before a joint code-breaking session. The ABR profiling test for schizophrenia identified schizophrenia patients versus controls with a sensitivity of 84.6% and a specificity of 93.1%. The ADHD test identified patients with adult ADHD versus controls with a sensitivity of 87.5% and a specificity of 91.4%. The ABR profiling tests discriminated schizophrenia and ADHD versus healthy controls with high sensitivity and specificity. The methods deserve to be further explored in larger clinical studies including a broad range of psychiatric disorders to determine their utility as potential diagnostic biomarkers.

  11. On the single sweep processing of auditory brainstem responses: click vs. chirp stimulations and active vs. passive electrodes.

    PubMed

    Corona-Strauss, Farah I; Delb, Wolfgang; Bloching, Marc; Strauss, Daniel J

    2008-01-01

    We have recently shown that click evoked auditory brainstem responses (ABRs) single sweeps can efficiently be processed by a hybrid novelty detection system. This approach allowed for the objective detection of hearing thresholds in a fraction of time of conventional schemes, making it appropriate for the efficient implementation of newborn hearing screening procedures. It is the objective of this study to evaluate whether this approach might further be improved by different stimulation paradigms and electrode settings. In particular, we evaluate chirp stimulations which compensate the basilar-membrane dispersion and active electrodes which are less sensitive to movements. This is the first study which is directed to a single sweep processing of chirp evoked ABRs. By concentrating on transparent features and a minimum number of adjustable parameters, we present an objective comparison of click vs.chirp stimulations and active vs. passive electrodes in the ultrafast ABR detection. We show that chirp evoked brainstem responses and active electrodes might improve the single sweeps analysis of ABRs.Consequently, we conclude that a single sweep processing of ABRs for the objective determination of hearing thresholds can further be improved by the use of optimized chirp stimulations and active electrodes.

  12. How well does your model capture the terrestrial ecosystem dynamics of the Arctic-Boreal Region?

    NASA Astrophysics Data System (ADS)

    Stofferahn, E.; Fisher, J. B.; Hayes, D. J.; Huntzinger, D. N.; Schwalm, C.

    2016-12-01

    The Arctic-Boreal Region (ABR) is a major source of uncertainties for terrestrial biosphere model (TBM) simulations. These uncertainties are precipitated by a lack of observational data from the region, affecting the parameterizations of cold environment processes in the models. Addressing these uncertainties requires a coordinated effort of data collection and integration of the following key indicators of the ABR ecosystem: disturbance, flora / fauna and related ecosystem function, carbon pools and biogeochemistry, permafrost, and hydrology. We are developing a model-data integration framework for NASA's Arctic Boreal Vulnerability Experiment (ABoVE), wherein data collection for the key ABoVE indicators is driven by matching observations and model outputs to the ABoVE indicators. The data are used as reference datasets for a benchmarking system which evaluates TBM performance with respect to ABR processes. The benchmarking system utilizes performance metrics to identify intra-model and inter-model strengths and weaknesses, which in turn provides guidance to model development teams for reducing uncertainties in TBM simulations of the ABR. The system is directly connected to the International Land Model Benchmarking (ILaMB) system, as an ABR-focused application.

  13. Cochlear Microphonic and Summating Potential Responses from Click-Evoked Auditory Brain Stem Responses in High-Risk and Normal Infants.

    PubMed

    Hunter, Lisa L; Blankenship, Chelsea M; Gunter, Rebekah G; Keefe, Douglas H; Feeney, M Patrick; Brown, David K; Baroch, Kelly

    2018-05-01

    Examination of cochlear and neural potentials is necessary to assess sensory and neural status in infants, especially those cared for in neonatal intensive care units (NICU) who have high rates of hyperbilirubinemia and thus are at risk for auditory neuropathy (AN). The purpose of this study was to determine whether recording parameters commonly used in click-evoked auditory brain stem response (ABR) are useful for recording cochlear microphonic (CM) and Wave I in infants at risk for AN. Specifically, we analyzed CM, summating potential (SP), and Waves I, III, and V. The overall aim was to compare latencies and amplitudes of evoked responses in infants cared for in NICUs with infants in a well-baby nursery (WBN), both of which passed newborn hearing screening. This is a prospective study in which infants who passed ABR newborn hearing screening were grouped based on their birth history (WBN and NICU). All infants had normal hearing status when tested with diagnostic ABR at about one month of age, corrected for prematurity. Thirty infants (53 ears) from the WBN [mean corrected age at test = 5.0 weeks (wks.)] and thirty-two infants (59 ears) from the NICU (mean corrected age at test = 5.7 wks.) with normal hearing were included in this study. In addition, two infants were included as comparative case studies, one that was diagnosed with AN and another case that was diagnosed with bilateral sensorineural hearing loss (SNHL). Diagnostic ABR, including click and tone-burst air- and bone-conduction stimuli were recorded. Peak Waves I, III, and V; SP; and CM latency and amplitude (peak to trough) were measured to determine if there were differences in ABR and electrocochleography (ECochG) variables between WBN and NICU infants. No significant group differences were found between WBN and NICU groups for ABR waveforms, CM, or SP, including amplitude and latency values. The majority (75%) of the NICU group had hyperbilirubinemia, but overall, they did not show evidence of effects in their ECochG or ABR responses when tested at about one-month corrected age. These data may serve as a normative sample for NICU and well infant ECochG and ABR latencies at one-month corrected age. Two infant case studies, one diagnosed with AN and another with SNHL demonstrated the complexity of using ECochG and otoacoustic emissions to assess the risk of AN in individual cases. CM and SPs can be readily measured using standard click stimuli in both well and NICU infants. Normative ranges for latency and amplitude are useful for interpreting ECochG and ABR components. Inclusion of ECochG and ABR tests in a test battery that also includes otoacoustic emission and acoustic reflex tests may provide a more refined assessment of the risks of AN and SNHL in infants. American Academy of Audiology.

  14. Identification of Dynamic Patterns of Speech-Evoked Auditory Brainstem Response Based on Ensemble Empirical Mode Decomposition and Nonlinear Time Series Analysis Methods

    NASA Astrophysics Data System (ADS)

    Mozaffarilegha, Marjan; Esteki, Ali; Ahadi, Mohsen; Nazeri, Ahmadreza

    The speech-evoked auditory brainstem response (sABR) shows how complex sounds such as speech and music are processed in the auditory system. Speech-ABR could be used to evaluate particular impairments and improvements in auditory processing system. Many researchers used linear approaches for characterizing different components of sABR signal, whereas nonlinear techniques are not applied so commonly. The primary aim of the present study is to examine the underlying dynamics of normal sABR signals. The secondary goal is to evaluate whether some chaotic features exist in this signal. We have presented a methodology for determining various components of sABR signals, by performing Ensemble Empirical Mode Decomposition (EEMD) to get the intrinsic mode functions (IMFs). Then, composite multiscale entropy (CMSE), the largest Lyapunov exponent (LLE) and deterministic nonlinear prediction are computed for each extracted IMF. EEMD decomposes sABR signal into five modes and a residue. The CMSE results of sABR signals obtained from 40 healthy people showed that 1st, and 2nd IMFs were similar to the white noise, IMF-3 with synthetic chaotic time series and 4th, and 5th IMFs with sine waveform. LLE analysis showed positive values for 3rd IMFs. Moreover, 1st, and 2nd IMFs showed overlaps with surrogate data and 3rd, 4th and 5th IMFs showed no overlap with corresponding surrogate data. Results showed the presence of noisy, chaotic and deterministic components in the signal which respectively corresponded to 1st, and 2nd IMFs, IMF-3, and 4th and 5th IMFs. While these findings provide supportive evidence of the chaos conjecture for the 3rd IMF, they do not confirm any such claims. However, they provide a first step towards an understanding of nonlinear behavior of auditory system dynamics in brainstem level.

  15. Growth and development of Arabidopsis in the Advanced Biological Research System (ABRS) hardware designed for the International Space Station

    NASA Astrophysics Data System (ADS)

    Savidge, Rodney

    Wild type (Col 0) Arabidopsis thaliana were grown in a growth chamber within the single mid-deck sized Advanced Biological Research System (ABRS) spaceflight hardware developed by NASA Kennedy Space Center. Before beginning this experiment, the plants, each rooted in individual transferable tubes containing nutrients, were cultivated hydroponically on halfstrength Hoagland's solution beneath either LED lighting similar to that provided by the ABRS growth chamber or white fluorescent lighting. The leaves of the basal whorl of plants pre-grown in ABRS lighting were small and purplish at the start of the experiment, whereas those under fluorescent lighting were larger and green. The plants were transferred to the ABRS soon after their inflorescence axes had started to elongate, and thereafter they were maintained under preset conditions (22 o C, approximately 1500 ppm CO2 , predominantly 125 µmol m-2 s-1 PAR) with pulses of water provided at 1-3 d intervals (as needed) to the module into which the root tubes were inserted. That module was pre-treated with half-strength Hoagland's nutrient solution on day 0, but no additional nutrients were provided the plants thereafter. Strong primary growth of all inflorescence stems occurred soon after initiating the ABRS experiment, and the plants began forming an overarching canopy of flowering stems beneath the LED lighting module within two weeks. After 38 days the root module was littered with seeds, siliques and abscised leaves, but all plants remained alive. Plants pre-grown in ABRS lighting were more advanced toward senescence, and leaves and stems of plants pre-grown in fluorescent lighting although greener were also acquiring a purplish hue. Microscopy revealed that the flowering stems achieved no secondary growth; however, progressive inward conversion of pith parenchyma into sclerenchyma cells did occur resulting in the inflorescence stems becoming abnormally woody.

  16. Nonleachable Imidazolium-Incorporated Composite for Disruption of Bacterial Clustering, Exopolysaccharide-Matrix Assembly, and Enhanced Biofilm Removal.

    PubMed

    Hwang, Geelsu; Koltisko, Bernard; Jin, Xiaoming; Koo, Hyun

    2017-11-08

    Surface-grown bacteria and production of an extracellular polymeric matrix modulate the assembly of highly cohesive and firmly attached biofilms, making them difficult to remove from solid surfaces. Inhibition of cell growth and inactivation of matrix-producing bacteria can impair biofilm formation and facilitate removal. Here, we developed a novel nonleachable antibacterial composite with potent antibiofilm activity by directly incorporating polymerizable imidazolium-containing resin (antibacterial resin with carbonate linkage; ABR-C) into a methacrylate-based scaffold (ABR-modified composite; ABR-MC) using an efficient yet simplified chemistry. Low-dose inclusion of imidazolium moiety (∼2 wt %) resulted in bioactivity with minimal cytotoxicity without compromising mechanical integrity of the restorative material. The antibiofilm properties of ABR-MC were assessed using an exopolysaccharide-matrix-producing (EPS-matrix-producing) oral pathogen (Streptococcus mutans) in an experimental biofilm model. Using high-resolution confocal fluorescence imaging and biophysical methods, we observed remarkable disruption of bacterial accumulation and defective 3D matrix structure on the surface of ABR-MC. Specifically, the antibacterial composite impaired the ability of S. mutans to form organized bacterial clusters on the surface, resulting in altered biofilm architecture with sparse cell accumulation and reduced amounts of EPS matrix (versus control composite). Biofilm topology analyses on the control composite revealed a highly organized and weblike EPS structure that tethers the bacterial clusters to each other and to the surface, forming a highly cohesive unit. In contrast, such a structured matrix was absent on the surface of ABR-MC with mostly sparse and amorphous EPS, indicating disruption in the biofilm physical stability. Consistent with lack of structural organization, the defective biofilm on the surface of ABR-MC was readily detached when subjected to low shear stress, while most of the biofilm biomass remained on the control surface. Altogether, we demonstrate a new nonleachable antibacterial composite with excellent antibiofilm activity without affecting its mechanical properties, which may serve as a platform for development of alternative antifouling biomaterials.

  17. Evoked potential recording during echolocation in a false killer whale Pseudorca crassidens (L)

    NASA Astrophysics Data System (ADS)

    Supin, Alexander Ya.; Nachtigall, Paul E.; Pawloski, Jeffrey; Au, Whitlow W. L.

    2003-05-01

    Auditory brainstem responses (ABRs) were recorded in a false killer whale while the animal echolocated a target. The ABR collection was triggered by echolocation clicks of the animal. In these conditions, the recorded ABR pattern contained a duplicate set of waves. A comparison of ABR wave delays recorded during echolocation with those recorded during regular external stimulation with experimenter generated clicks showed that the first set of waves may be a response to the emitted click whereas the second one may be a response to the echo. Both responses, to the emitted click and to the echo, were of comparable amplitude in spite of the intensity difference of these two sounds that may differ by more than 40 dB near the animal's head. This finding indicates the presence of some mechanism of releasing responses to echoes from masking by loud emitted clicks. The evoked-potential method may be productive to investigate these mechanisms.

  18. Performance of an Anaerobic Baffled Reactor (ABR) in treatment of cassava wastewater

    PubMed Central

    Ferraz, Fernanda M.; Bruni, Aline T.; Del Bianchi, Vanildo L.

    2009-01-01

    The performance of an anaerobic baffled reactor (ABR) was evaluated in the treatment of cassava wastewater, a pollutant residue. An ABR divided in four equal volume compartments (total volume 4L) and operated at 35ºC was used in cassava wastewater treatment. Feed tank chemical oxygen demand (COD) was varied from 2000 to 7000 mg L-1 and it was evaluated the most appropriated hydraulic retention time (HRT) for the best performance on COD removal. The ABR was evaluated by analysis of COD (colorimetric method), pH, turbidity, total and volatile solids, alkalinity and acidity. Principal component analysis (PCA) was carried to better understand data obtained. The system showed buffering ability as acidity decreased along compartments while alkalinity and pH values were increased. There was particulate material retention and COD removal varied from 83 to 92% for HRT of 3.5 days. PMID:24031316

  19. Establishing a distributed national research infrastructure providing bioinformatics support to life science researchers in Australia.

    PubMed

    Schneider, Maria Victoria; Griffin, Philippa C; Tyagi, Sonika; Flannery, Madison; Dayalan, Saravanan; Gladman, Simon; Watson-Haigh, Nathan; Bayer, Philipp E; Charleston, Michael; Cooke, Ira; Cook, Rob; Edwards, Richard J; Edwards, David; Gorse, Dominique; McConville, Malcolm; Powell, David; Wilkins, Marc R; Lonie, Andrew

    2017-06-30

    EMBL Australia Bioinformatics Resource (EMBL-ABR) is a developing national research infrastructure, providing bioinformatics resources and support to life science and biomedical researchers in Australia. EMBL-ABR comprises 10 geographically distributed national nodes with one coordinating hub, with current funding provided through Bioplatforms Australia and the University of Melbourne for its initial 2-year development phase. The EMBL-ABR mission is to: (1) increase Australia's capacity in bioinformatics and data sciences; (2) contribute to the development of training in bioinformatics skills; (3) showcase Australian data sets at an international level and (4) enable engagement in international programs. The activities of EMBL-ABR are focussed in six key areas, aligning with comparable international initiatives such as ELIXIR, CyVerse and NIH Commons. These key areas-Tools, Data, Standards, Platforms, Compute and Training-are described in this article. © The Author 2017. Published by Oxford University Press.

  20. The Role and Regulation of ABI5 (ABA-Insensitive 5) in Plant Development, Abiotic Stress Responses and Phytohormone Crosstalk

    PubMed Central

    Skubacz, Anna; Daszkowska-Golec, Agata; Szarejko, Iwona

    2016-01-01

    ABA Insensitive 5 (ABI5) is a basic leucine zipper transcription factor that plays a key role in the regulation of seed germination and early seedling growth in the presence of ABA and abiotic stresses. ABI5 functions in the core ABA signaling, which is composed of PYR/PYL/RCAR receptors, PP2C phosphatases and SnRK2 kinases, through the regulation of the expression of genes that contain the ABSCISIC ACID RESPONSE ELEMENT (ABRE) motif within their promoter region. The regulated targets include stress adaptation genes, e.g., LEA proteins. However, the expression and activation of ABI5 is not only dependent on the core ABA signaling. Many transcription factors such as ABI3, ABI4, MYB7 and WRKYs play either a positive or a negative role in the regulation of ABI5 expression. Additionally, the stability and activity of ABI5 are also regulated by other proteins through post-translational modifications such as phosphorylation, ubiquitination, sumoylation and S-nitrosylation. Moreover, ABI5 also acts as an ABA and other phytohormone signaling integrator. Components of auxin, cytokinin, gibberellic acid, jasmonate and brassinosteroid signaling and metabolism pathways were shown to take part in ABI5 regulation and/or to be regulated by ABI5. Monocot orthologs of AtABI5 have been identified. Although their roles in the molecular and physiological adaptations during abiotic stress have been elucidated, knowledge about their detailed action still remains elusive. Here, we describe the recent advances in understanding the action of ABI5 in early developmental processes and the adaptation of plants to unfavorable environmental conditions. We also focus on ABI5 relation to other phytohormones in the abiotic stress response of plants. PMID:28018412

  1. MEF2 Cooperates With Forskolin/cAMP and GATA4 to Regulate Star Gene Expression in Mouse MA-10 Leydig Cells.

    PubMed

    Daems, Caroline; Di-Luoffo, Mickaël; Paradis, Élise; Tremblay, Jacques J

    2015-07-01

    In Leydig cells, steroidogenic acute regulatory protein (STAR) participates in cholesterol shuttling from the outer to the inner mitochondrial membrane, the rate-limiting step in steroidogenesis. Steroid hormone biosynthesis and steroidogenic gene expression are regulated by LH, which activates various signaling pathways and transcription factors, including cAMP/Ca(2+)/CAMK (Ca(2+)/calmodulin-dependent kinase)-myocyte enhancer factor 2 (MEF2). The 4 MEF2 transcription factors are essential regulators of cell differentiation and organogenesis in numerous tissues. Recently, MEF2 was identified in Sertoli and Leydig cells of the testis. Here, we report that MEF2 regulates steroidogenesis in mouse MA-10 Leydig cells by acting on the Star gene. In MA-10 cells depleted of MEF2 using siRNAs (small interfering RNAs), STAR protein levels, Star mRNA levels, and promoter activity were significantly decreased. On its own, MEF2 did not activate the mouse Star promoter but was found to cooperate with forskolin/cAMP. By chromatin immunoprecipitation and DNA precipitation assays, we confirmed MEF2 binding to a consensus element located at -232 bp of the Star promoter. Mutation or deletion of the MEF2 element reduced but did not abrogate the MEF2/cAMP cooperation, indicating that MEF2 cooperates with other DNA-bound transcription factor(s). We identified GATA4 (GATA binding protein 4) as a partner for MEF2 in Leydig cells, because mutation of the GATA element abrogated the MEF2/cAMP cooperation on a reporter lacking a MEF2 element. MEF2 and GATA4 interact as revealed by coimmunoprecipitation, and MEF2 and GATA4 transcriptionally cooperate on the Star promoter. Altogether, our results define MEF2 as a novel regulator of steroidogenesis and Star transcription in Leydig cells and identify GATA4 as a key partner for MEF2-mediated action.

  2. 7 CFR 4284.620 - Applicant eligibility.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE GRANTS Rural Business Opportunity Grants § 4284.620... dependable sources of revenue or a successful history of raising revenue sufficient to meet cash requirements...

  3. Tinnitus with a normal audiogram: Relation to noise exposure but no evidence for cochlear synaptopathy.

    PubMed

    Guest, Hannah; Munro, Kevin J; Prendergast, Garreth; Howe, Simon; Plack, Christopher J

    2017-02-01

    In rodents, exposure to high-level noise can destroy synapses between inner hair cells and auditory nerve fibers, without causing hair cell loss or permanent threshold elevation. Such "cochlear synaptopathy" is associated with amplitude reductions in wave I of the auditory brainstem response (ABR) at moderate-to-high sound levels. Similar ABR results have been reported in humans with tinnitus and normal audiometric thresholds, leading to the suggestion that tinnitus in these cases might be a consequence of synaptopathy. However, the ABR is an indirect measure of synaptopathy and it is unclear whether the results in humans reflect the same mechanisms demonstrated in rodents. Measures of noise exposure were not obtained in the human studies, and high frequency audiometric loss may have impacted ABR amplitudes. To clarify the role of cochlear synaptopathy in tinnitus with a normal audiogram, we recorded ABRs, envelope following responses (EFRs), and noise exposure histories in young adults with tinnitus and matched controls. Tinnitus was associated with significantly greater lifetime noise exposure, despite close matching for age, sex, and audiometric thresholds up to 14 kHz. However, tinnitus was not associated with reduced ABR wave I amplitude, nor with significant effects on EFR measures of synaptopathy. These electrophysiological measures were also uncorrelated with lifetime noise exposure, providing no evidence of noise-induced synaptopathy in this cohort, despite a wide range of exposures. In young adults with normal audiograms, tinnitus may be related not to cochlear synaptopathy but to other effects of noise exposure. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Cost-effectiveness analysis of TOC removal from slaughterhouse wastewater using combined anaerobic-aerobic and UV/H2O2 processes.

    PubMed

    Bustillo-Lecompte, Ciro Fernando; Mehrvar, Mehrab; Quiñones-Bolaños, Edgar

    2014-02-15

    The objective of this study is to evaluate the operating costs of treating slaughterhouse wastewater (SWW) using combined biological and advanced oxidation processes (AOPs). This study compares the performance and the treatment capability of an anaerobic baffled reactor (ABR), an aerated completely mixed activated sludge reactor (AS), and a UV/H2O2 process, as well as their combination for the removal of the total organic carbon (TOC). Overall efficiencies are found to be up to 75.22, 89.47, 94.53, 96.10, 96.36, and 99.98% for the UV/H2O2, ABR, AS, combined AS-ABR, combined ABR-AS, and combined ABR-AS-UV/H2O2 processes, respectively. Due to the consumption of electrical energy and reagents, operating costs are calculated at optimal conditions of each process. A cost-effectiveness analysis (CEA) is performed at optimal conditions for the SWW treatment by optimizing the total electricity cost, H2O2 consumption, and hydraulic retention time (HRT). The combined ABR-AS-UV/H2O2 processes have an optimal TOC removal of 92.46% at an HRT of 41 h, a cost of $1.25/kg of TOC removed, and $11.60/m(3) of treated SWW. This process reaches a maximum TOC removal of 99% in 76.5 h with an estimated cost of $2.19/kg TOC removal and $21.65/m(3) treated SWW, equivalent to $6.79/m(3) day. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Preoperative characteristics of auditory brainstem response in acoustic neuroma with useful hearing: importance as a preliminary investigation for intraoperative monitoring.

    PubMed

    Aihara, Noritaka; Murakami, Shingo; Takahashi, Mariko; Yamada, Kazuo

    2014-01-01

    We classified the results of preoperative auditory brainstem response (ABR) in 121 patients with useful hearing and considered the utility of preoperative ABR as a preliminary assessment for intraoperative monitoring. Wave V was confirmed in 113 patients and was not confirmed in 8 patients. Intraoperative ABR could not detect wave V in these 8 patients. The 8 patients without wave V were classified into two groups (flat and wave I only), and the reason why wave V could not be detected may have differed between the groups. Because high-frequency hearing was impaired in flat patients, an alternative to click stimulation may be more effective. Monitoring cochlear nerve action potential (CNAP) may be useful because CNAP could be detected in 4 of 5 wave I only patients. Useful hearing was preserved after surgery in 1 patient in the flat group and 2 patients in wave I only group. Among patients with wave V, the mean interaural latency difference of wave V was 0.88 ms in Class A (n = 57) and 1.26 ms in Class B (n = 56). Because the latency of wave V is already prolonged before surgery, to estimate delay in wave V latency during surgery probably underestimates cochlear nerve damage. Recording intraoperative ABR is indispensable to avoid cochlear nerve damage and to provide information for surgical decisions. Confirming the condition of ABR before surgery helps to solve certain problems, such as choosing to monitor the interaural latency difference of wave V, CNAP, or alternative sound-evoked ABR.

  6. 75 FR 31508 - Notice of Projects Approved for Consumptive Uses of Water

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-03

    ... County, Pa.; Approval Date: April 13, 2010. 23. Chesapeake Appalachia, LLC, Pad ID: Henry, ABR-20100423..., Susquehanna County, Pa.; Approval Date: April 14, 2010. 26. EOG Resources, Inc., Pad ID: JENKINS 1H, ABR...

  7. 75 FR 4901 - Notice of Projects Approved for Consumptive Uses of Water

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-29

    ... up to 5.000 mgd; Approval Date: December 14, 2009. 43. East Resources, Inc., Pad ID: Jenkins 523, ABR... Resources, Inc., Pad ID: Marshlands K. Thomas Unit 1, ABR-20091231, Elk Township, Tioga County, Pa...

  8. The relationship between loudness intensity functions and the click-ABR wave V latency.

    PubMed

    Serpanos, Y C; O'Malley, H; Gravel, J S

    1997-10-01

    To assess the relationship of loudness growth and the click-evoked auditory brain stem response (ABR) wave V latency-intensity function (LIF) in listeners with normal hearing or cochlear hearing loss. The effect of hearing loss configuration on the intensity functions was also examined. Behavioral and electrophysiological intensity functions were obtained using click stimuli of comparable intensities in listeners with normal hearing (Group I; n = 10), and cochlear hearing loss of flat (Group II; n = 10) or sloping (Group III; n = 10) configurations. Individual intensity functions were obtained from measures of loudness growth using the psychophysical methods of absolute magnitude estimation and production of loudness (geometrically averaged to provide the measured loudness function), and from the wave V latency measures of the ABR. Slope analyses for the behavioral and electrophysiological intensity functions were separately performed by group. The loudness growth functions for the groups with cochlear hearing loss approximated the normal function at high intensities, with overall slope values consistent with those reported from previous psychophysical research. The ABR wave V LIF for the group with a flat configuration of cochlear hearing loss approximated the normal function at high intensities, and was displaced parallel to the normal function for the group with sloping configuration. The relationship between the behavioral and electrophysiological intensity functions was examined at individual intensities across the range of the functions for each subject. A significant relationship was obtained between loudness and the ABR wave V LIFs for the groups with normal hearing and flat configuration of cochlear hearing loss; the association was not significant (p = 0.10) for the group with a sloping configuration of cochlear hearing loss. The results of this study established a relationship between loudness and the ABR wave V latency for listeners with normal hearing, and flat cochlear hearing loss. In listeners with a sloping configuration of cochlear hearing loss, the relationship was not significant. This suggests that the click-evoked ABR may be used to estimate loudness growth at least for individuals with normal hearing and those with a flat configuration of cochlear hearing loss. Predictive equations were derived to estimate loudness growth for these groups. The use of frequency-specific stimuli may provide more precise information on the nature of the relationship between loudness growth and the ABR wave V latency, particularly for listeners with sloping configurations of cochlear hearing loss.

  9. Click-evoked auditory brainstem responses and autism spectrum disorder: A meta-analytic review.

    PubMed

    Talge, Nicole M; Tudor, Brooke M; Kileny, Paul R

    2018-06-01

    Behavior does not differentiate ASD risk prior to 12 months of age, but biomarkers may inform risk before symptoms emerge. Click-evoked auditory brainstem responses (ABRs) may be worth consideration due to their measurement properties (noninvasiveness; reliability) and conceptual features (well-characterized neural generators), but participant characteristics and assessment protocols vary considerably across studies. Our goal is to perform a meta-analysis of the association between ABRs and ASD. Following an electronic database search (PubMed, Medline, PsycInfo, PsycArticles), we included papers that were written in English, included ASD and typically-developing (TD) groups, and reported the information needed to calculate standardized mean differences (Hedges's g) for at least one ABR latency component (I, III, V, I-III, III-V, I-V). We weighted and averaged effect sizes across conditions and subsets of participants to yield one estimate per component per study. We then performed random-effects regressions to generate component-specific estimates. ASD was associated with longer ABR latencies for Waves III (g = 0.5, 95% CI 0.1, 0.9), V (g = 0.7, 95% CI 0.3, 1.1), I-III (g = 0.7, 95% CI 0.2, 1.2), and I-V (g = 0.6, 95% CI 0.2, 1.0). All components showed significant heterogeneity. Associations were strongest among participants ≤8 years of age and those without middle ear abnormalities or elevated auditory thresholds. In sum, associations between ABRs and ASD are medium-to-large in size, but exhibit heterogeneity. Identifying sources of heterogeneity is challenging, however, due to power limitations and co-occurrence of sample/design characteristics across studies. Research addressing the above limitations is crucial to determining the etiologic and/or prognostic value of ABRs for ASD. Autism Res 2018, 11: 916-927. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. Auditory brainstem responses (ABR) may be associated with ASD, but participant characteristics and assessment protocols vary considerably across individual studies. Our goal is to combine the results across these studies to facilitate clarity on the topic. Doing so represents a first step in evaluating whether ABRs yield potential for informing the etiology of ASD risk and/or ASD symptom profiles. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

  10. Cooperative Regulation of the Interferon Regulatory Factor-1 Tumor Suppressor Protein by Core Components of the Molecular Chaperone Machinery*

    PubMed Central

    Narayan, Vikram; Eckert, Mirjam; Zylicz, Alicja; Zylicz, Maciej; Ball, Kathryn L.

    2009-01-01

    Our understanding of the post-translational processes involved in regulating the interferon regulatory factor-1 (IRF-1) tumor suppressor protein is limited. The introduction of mutations within the C-terminal Mf1 domain (amino acids 301–325) impacts on IRF-1-mediated gene repression and growth suppression as well as the rate of IRF-1 degradation. However, nothing is known about the proteins that interact with this region to modulate IRF-1 function. A biochemical screen for Mf1-interacting proteins has identified an LXXLL motif that is required for binding of Hsp70 family members and cooperation with Hsp90 to regulate IRF-1 turnover and activity. These conclusions are supported by the finding that Hsp90 inhibitors suppress IRF-1-dependent transcription shortly after treatment, although at later time points inhibition of Hsp90 leads to an Hsp70-dependent depletion of nuclear IRF-1. Conversely, the half-life of IRF-1 is increased by Hsp90 in an ATPase-dependent manner leading to the accumulation of nuclear but not cytoplasmic IRF-1. This study begins to elucidate the role of the Mf1 domain of IRF-1 in orchestrating the recruitment of regulatory factors that can impact on both its turnover and transcriptional activity. PMID:19502235

  11. Cooperative STAT/NF-κB signaling regulates lymphoma metabolic reprogramming and aberrant GOT2 expression.

    PubMed

    Feist, Maren; Schwarzfischer, Philipp; Heinrich, Paul; Sun, Xueni; Kemper, Judith; von Bonin, Frederike; Perez-Rubio, Paula; Taruttis, Franziska; Rehberg, Thorsten; Dettmer, Katja; Gronwald, Wolfram; Reinders, Jörg; Engelmann, Julia C; Dudek, Jan; Klapper, Wolfram; Trümper, Lorenz; Spang, Rainer; Oefner, Peter J; Kube, Dieter

    2018-04-17

    Knowledge of stromal factors that have a role in the transcriptional regulation of metabolic pathways aside from c-Myc is fundamental to improvements in lymphoma therapy. Using a MYC-inducible human B-cell line, we observed the cooperative activation of STAT3 and NF-κB by IL10 and CpG stimulation. We show that IL10 + CpG-mediated cell proliferation of MYC low cells depends on glutaminolysis. By 13 C- and 15 N-tracing of glutamine metabolism and metabolite rescue experiments, we demonstrate that GOT2 provides aspartate and nucleotides to cells with activated or aberrant Jak/STAT and NF-κB signaling. A model of GOT2 transcriptional regulation is proposed, in which the cooperative phosphorylation of STAT3 and direct joint binding of STAT3 and p65/NF-κB to the proximal GOT2 promoter are important. Furthermore, high aberrant GOT2 expression is prognostic in diffuse large B-cell lymphoma underscoring the current findings and importance of stromal factors in lymphoma biology.

  12. The Evolution of Quorum Sensing as a Mechanism to Infer Kinship

    PubMed Central

    Schluter, Jonas; Schoech, Armin P.; Foster, Kevin R.; Mitri, Sara

    2016-01-01

    Bacteria regulate many phenotypes via quorum sensing systems. Quorum sensing is typically thought to evolve because the regulated cooperative phenotypes are only beneficial at certain cell densities. However, quorum sensing systems are also threatened by non-cooperative “cheaters” that may exploit quorum-sensing regulated cooperation, which begs the question of how quorum sensing systems are maintained in nature. Here we study the evolution of quorum sensing using an individual-based model that captures the natural ecology and population structuring of microbial communities. We first recapitulate the two existing observations on quorum sensing evolution: density-dependent benefits favor quorum sensing but competition and cheating will destabilize it. We then model quorum sensing in a dense community like a biofilm, which reveals a novel benefit to quorum sensing that is intrinsically evolutionarily stable. In these communities, competing microbial genotypes gradually segregate over time leading to positive correlation between density and genetic similarity between neighboring cells (relatedness). This enables quorum sensing to track genetic relatedness and ensures that costly cooperative traits are only activated once a cell is safely surrounded by clonemates. We hypothesize that under similar natural conditions, the benefits of quorum sensing will not result from an assessment of density but from the ability to infer kinship. PMID:27120081

  13. Nonlinear Processing of Auditory Brainstem Response

    DTIC Science & Technology

    2001-10-25

    Kraków, Poland Abstract: - Auditory brainstem response potentials (ABR) are signals calculated from the EEG signals registered as responses to an...acoustic activation of the auditory system. The ABR signals provide an objective, diagnostic method, widely applied in examinations of hearing organs

  14. Appearance-based rejection sensitivity as a mediator of the relationship between symptoms of social anxiety and disordered eating cognitions and behaviors.

    PubMed

    Linardon, Jake; Braithwaite, Rachel; Cousins, Rachel; Brennan, Leah

    2017-12-01

    Previous research has established a robust relationship between symptoms of social anxiety and disordered eating. However, the mechanisms that may underpin this relationship are unclear. Appearance-based rejection sensitivity (ABRS)-the tendency to anxiously expect and overreact to signs of appearance-based rejection-may be a crucial explanatory mechanism, as ABRS has been shown to maintain social anxiety symptoms and predict disordered eating. We therefore tested whether ABRS mediated the relationship between social anxiety symptoms and various indices of disordered eating (over-evaluation of weight/shape, restraint, binge eating, compulsive exercise, and vomiting). Data from community-based females (n=299) and males (n=87) were analyzed. ABRS was shown to mediate the relationship between social anxiety and the over-evaluation, restraint, binge eating, and compulsive exercise frequency, but not vomiting. These effects also occurred for both females and males separately. Findings demonstrated that ABRS may be an important mechanism explaining why socially anxious individuals report elevated symptoms of disordered eating. Future research testing all proposed mediating variables of the social anxiety-disordered eating link in a single, integrative model is required to identify the most influential mechanisms driving this relationship. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Comparison of ABR response amplitude, test time, and estimation of hearing threshold using frequency specific chirp and tone pip stimuli in newborns.

    PubMed

    Ferm, Inga; Lightfoot, Guy; Stevens, John

    2013-06-01

    To evaluate the auditory brainstem response (ABR) amplitudes evoked by tone pip and narrowband chirp (NB CE-Chirp) stimuli when testing post-screening newborns and to determine the difference in estimated hearing level correction values. Tests were performed with tone pips and NB CE-Chirps at 4 kHz or 1 kHz. The response amplitude, response quality (Fmp), and residual noise were compared for both stimuli. Thirty babies (42 ears) who passed our ABR discharge criterion at 4 kHz following referral from their newborn hearing screen. Overall, NB CE-Chirp responses were 64% larger than the tone pip responses, closer to those evoked by clicks. Fmp was significantly higher for NB CE-Chirps. It is anticipated that there could be significant reductions in test time for the same signal to noise ratio by using NB CE-Chirps when testing newborns. This effect may vary in practice and is likely to be most beneficial for babies with low amplitude ABR responses. We propose that the ABR nHL threshold to eHL correction for NB CE-Chirps should be approximately 5 dB less than the corrections for tone pips at 4 and 1 kHz.

  16. Exploring the Relationship between Physiological Measures of Cochlear and Brainstem Function

    PubMed Central

    Dhar, S.; Abel, R.; Hornickel, J.; Nicol, T.; Skoe, E.; Zhao, W.; Kraus, N.

    2009-01-01

    Objective Otoacoustic emissions and the speech-evoked auditory brainstem response are objective indices of peripheral auditory physiology and are used clinically for assessing hearing function. While each measure has been extensively explored, their interdependence and the relationships between them remain relatively unexplored. Methods Distortion product otoacoustic emissions (DPOAE) and speech-evoked auditory brainstem responses (sABR) were recorded from 28 normal-hearing adults. Through correlational analyses, DPOAE characteristics were compared to measures of sABR timing and frequency encoding. Data were organized into two DPOAE (Strength and Structure) and five brainstem (Onset, Spectrotemporal, Harmonics, Envelope Boundary, Pitch) composite measures. Results DPOAE Strength shows significant relationships with sABR Spectrotemporal and Harmonics measures. DPOAE Structure shows significant relationships with sABR Envelope Boundary. Neither DPOAE Strength nor Structure is related to sABR Pitch. Conclusions The results of the present study show that certain aspects of the speech-evoked auditory brainstem responses are related to, or covary with, cochlear function as measured by distortion product otoacoustic emissions. Significance These results form a foundation for future work in clinical populations. Analyzing cochlear and brainstem function in parallel in different clinical populations will provide a more sensitive clinical battery for identifying the locus of different disorders (e.g., language based learning impairments, hearing impairment). PMID:19346159

  17. Transcriptomic analysis of rice aleurone cells identified a novel abscisic acid response element.

    PubMed

    Watanabe, Kenneth A; Homayouni, Arielle; Gu, Lingkun; Huang, Kuan-Ying; Ho, Tuan-Hua David; Shen, Qingxi J

    2017-09-01

    Seeds serve as a great model to study plant responses to drought stress, which is largely mediated by abscisic acid (ABA). The ABA responsive element (ABRE) is a key cis-regulatory element in ABA signalling. However, its consensus sequence (ACGTG(G/T)C) is present in the promoters of only about 40% of ABA-induced genes in rice aleurone cells, suggesting other ABREs may exist. To identify novel ABREs, RNA sequencing was performed on aleurone cells of rice seeds treated with 20 μM ABA. Gibbs sampling was used to identify enriched elements, and particle bombardment-mediated transient expression studies were performed to verify the function. Gene ontology analysis was performed to predict the roles of genes containing the novel ABREs. This study revealed 2443 ABA-inducible genes and a novel ABRE, designated as ABREN, which was experimentally verified to mediate ABA signalling in rice aleurone cells. Many of the ABREN-containing genes are predicted to be involved in stress responses and transcription. Analysis of other species suggests that the ABREN may be monocot specific. This study also revealed interesting expression patterns of genes involved in ABA metabolism and signalling. Collectively, this study advanced our understanding of diverse cis-regulatory sequences and the transcriptomes underlying ABA responses in rice aleurone cells. © 2017 John Wiley & Sons Ltd.

  18. A study of adaptation mechanisms based on ABR recorded at high stimulation rate.

    PubMed

    Valderrama, Joaquin T; de la Torre, Angel; Alvarez, Isaac; Segura, Jose Carlos; Thornton, A Roger D; Sainz, Manuel; Vargas, Jose Luis

    2014-04-01

    This paper analyzes the fast and slow mechanisms of adaptation through a study of latencies and amplitudes on ABR recorded at high stimulation rates using the randomized stimulation and averaging (RSA) technique. The RSA technique allows a separate processing of auditory responses, and is used, in this study, to categorize responses according to the interstimulus interval (ISI) of their preceding stimulus. The fast and slow mechanisms of adaptation are analyzed by the separated responses methodology, whose underlying principles and mathematical basis are described in detail. The morphology of the ABR is influenced by both fast and slow mechanisms of adaptation. These results are consistent with previous animal studies based on spike rate. Both fast and slow mechanisms of adaptation are present in all subjects. In addition, the distribution of the jitter and the sequencing of the stimuli may be critical parameters when obtaining reliable ABRs. The separated responses methodology enables for the first time the analysis of the fast and slow mechanisms of adaptation in ABR obtained at stimulation rates greater than 100 Hz. The non-invasive nature of this methodology is appropriate for its use in humans. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  19. [The influence of click polarity and stimulation rate on the auditory evoked response in relation to age].

    PubMed

    Tarantino, V; Stura, M; Raspino, M; Conrad, E; Porcu, A

    1989-01-01

    In order to study the changes which occur in phase of the click stimulus and its relation to the stimulus repetition rate on the auditory brainstem response (ABR) as a function of age, the Authors recorded the ABR from the scalp's surface of 10 newborns and 40 infants, 3 months, 6 months, 1 year and 3 years old as well as from 10 normal adults. The stimulus was a square wave of 0.1 msec duration and 90 dBHL level. The stimulus equipment was calibrated twice under visual inspection to ensure that the C and R clicks resulted in an initial membrane deflection toward and from the ear drum respectively. No significant differences could be found for the latencies and amplitude in the C-R comparison. However, the mean values of the complete group of test subjects showed most intraindividual stability for the conventional click stimulation. The latency of the ABR with excitation of the cochlea seemed to be mainly determined by the internal oscillation sequence in the cochlea and not by the stimulus polarity. The amplitudes and latencies of the ABR components tend to decrease when the stimulus rate increases and the age decreases. The importance of the stimulus characteristics is discussed and some suggestions for clinical use of ABR are made.

  20. An ABA-responsive element in the AtSUC1 promoter is involved in the regulation of AtSUC1 expression.

    PubMed

    Hoth, Stefan; Niedermeier, Matthias; Feuerstein, Andrea; Hornig, Julia; Sauer, Norbert

    2010-09-01

    Abscisic acid (ABA) and sugars regulate many aspects of plant growth and development, and we are only just beginning to understand the complex interactions between ABA and sugar signaling networks. Here, we show that ABA-dependent transcription factors bind to the promoter of the Arabidopsis thaliana AtSUC1 (At1g71880) sucrose transporter gene in vitro. We present the characterization of a cis-regulatory element by truncation of the AtSUC1 promoter and by electrophoretic mobility shift assays that is identical to a previously characterized ABA-responsive element (ABRE). In yeast 1-hybrid analyses we identified ABI5 (AtbZIP39; At2g36270) and AREB3 (AtbZIP66; At3g56850) as potential interactors. Analyses of plants expressing the beta-glucuronidase reporter gene under the control of ABI5 or AREB3 promoter sequences demonstrated that both transcription factor genes are co-expressed with AtSUC1 in pollen and seedlings, the primary sites of AtSUC1 action. Mutational analyses of the identified cis-regulatory element verified its importance for AtSUC1 expression in young seedlings. In abi5-4 seedlings, we observed an increase of sucrose-dependent anthocyanin accumulation and AtSUC1 mRNA levels. This suggests that ABI5 prevents an overshoot of sucrose-induced AtSUC1 expression and confirmed a novel cross-link between sugar and ABA signaling.

  1. A novel zinc-finger protein with a proline-rich domain mediates ABA-regulated seed dormancy in Arabidopsis.

    PubMed

    He, Yuehui; Gan, Susheng

    2004-01-01

    Seed dormancy is an important developmental process that prevents pre-harvest sprouting in many grains and other seeds. Abscisic acid (ABA), a plant hormone, plays a crucial role in regulating dormancy but the underlying molecular regulatory mechanisms are not fully understood. An Arabidopsis zinc-finger gene, MEDIATOR OF ABA-REGULATED DORMANCY 1 ( MARD1 ) was identified and functionally analyzed. MARD1 expression is up-regulated by ABA. A T-DNA insertion in the promoter region downstream of two ABA-responsive elements (ABREs) renders MARD1 unable to respond to ABA. The mard1 seeds are less dormant and germinate in total darkness; their germination is resistant to external ABA at the stage of radicle protrusion. These results suggest that this novel zinc-finger protein with a proline-rich N-terminus is an important downstream component of the ABA signaling pathway that mediates ABA-regulated seed dormancy in Arabidopsis.

  2. Age-related changes in the auditory brainstem response.

    PubMed

    Konrad-Martin, Dawn; Dille, Marilyn F; McMillan, Garnett; Griest, Susan; McDermott, Daniel; Fausti, Stephen A; Austin, Donald F

    2012-01-01

    This cross-sectional study had two goals: (1) Identify and quantify the effects of aging on the auditory brainstem response (ABR); (2) Describe how click rate and hearing impairment modify effects of aging. RESEARCH DESIGN AND ANALYSIS: ABR measures were obtained from 131 predominately male Veteran participants aged 26 to 71 yr. Metrics analyzed include amplitude and latency for waves I, III, and V, and the I-V interpeak latency interval (IPI) at three repetition rates (11, 51, and 71 clicks/sec) using both polarities. In order to avoid confounding from missing data due to hearing impairment, participants had hearing thresholds <40 dB HL at 2 kHz and 70 dB HL at 4 kHz in at least one ear. Additionally, the median 2, 3, and 4 kHz pure tone threshold average (PTA2,3,4) for the sample, ∼17 dB HL, was used to delineate subgroups of better and worse hearing ears, and only the better hearing sample was modeled statistically. We modeled ABR responses using age, repetition rate, and PTA2,3,4 as covariates. Random effects were used to model correlation between the two ears of a subject and across repetition rates. Inferences regarding effects of aging on ABR measures at each rate were derived from the fitted model. Results were compared to data from subjects with poorer hearing. Aging substantially diminished amplitudes of all of the principal ABR peaks, largely independent of any threshold differences within the group. For waves I and III, age-related amplitude decrements were greatest at a low (11/sec) click rate. At the 11/sec rate, the model-based mean wave III amplitude was significantly smaller in older compared with younger subjects even after adjusting for wave I amplitude. Aging also increased ABR peak latencies, with significant shifts limited to early waves. The I-V IPI did not change with age. For both younger and older subjects, increasing click presentation rate significantly decreased amplitudes of early peaks and prolonged latencies of later peaks, resulting in increased IPIs. Advanced age did not enhance effects of rate. Instead, the rate effect on wave I and III amplitudes was attenuated for the older subjects due to reduced peak amplitudes at lower click rates. Compared with model predictions from the sample of better hearing subjects, mean ABR amplitudes were diminished in the group with poorer hearing, and wave V latencies were prolonged. In a sample of veterans, aging substantially reduced amplitudes of all principal ABR peaks, with significant latency shifts limited to waves I and III. Aging did not influence the I-V IPI even at high click rates, suggesting that the observed absolute latency changes associated with aging can be attributed to changes in auditory nerve input. In contrast, ABR amplitude changes with age are not adequately explained by changes in wave I. Results suggest that aging reduces the numbers and/or synchrony of contributing auditory nerve units. Results also support the concept that aging reduces the numbers, though perhaps not the synchrony, of central ABR generators. American Academy of Audiology.

  3. Global Trends in Adolescent Fertility, 1990-2012, in Relation to National Wealth, Income Inequalities, and Educational Expenditures.

    PubMed

    Santelli, John S; Song, Xiaoyu; Garbers, Samantha; Sharma, Vinit; Viner, Russell M

    2017-02-01

    National wealth, income inequalities, and expenditures on education can profoundly influence the health of a nation's women, children, and adolescents. We explored the association of trends in national socioeconomic status (SES) indicators with trends in adolescent birth rates (ABRs), by nation and region. An ecologic research design was employed using national-level data from the World Bank on birth rates per 1,000 women aged 15-19 years, national wealth (per capita gross domestic product or GDP), income inequality (Gini index), and expenditures on education as a percentage of GDP (EduExp). Data were available for 142 countries and seven regions for 1990-2012. Multiple linear regression for repeated measures with generalized estimating equations was used to examine independent associations. ABRs in 2012 varied >200-fold-with the highest rates in Sub-Saharan Africa and lowest rates in the Western Europe/Central Asia region. The median national ABR fell 40% from 72.4/1,000 in 1990 to 43.6/1,000 in 2012. The largest regional declines in ABR occurred in South Asia (70%), Europe/Central Asia (63%), and the Middle East/North Africa (53%)-regions with lower income inequality. In multivariable analyses considering change over time, ABRs were negatively associated with GDP and EduExp and positively associated with greater income inequality. ABRs have declined globally since 1990. Declines closely followed rising socioeconomic status and were greater where income inequalities were lower in 1990. Reducing poverty and income inequalities and increasing investments in education should be essential components of national policies to prevent adolescent childbearing. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  4. Limited Ventricular Preload is the Main Reason for Reduced Stress Reserve After Atrial Baffle Repair.

    PubMed

    Eicken, Andreas; Michel, Julia; Hager, Alfred; Tanase, Daniel; Kaemmerer, Harald; Cleuziou, Julie; Hess, John; Ewert, Peter

    2017-02-01

    The atrial baffle repair (ABR) significantly improved the fate of patients with transposition of the great arteries (TGA). However, these patients show impaired exercise tolerance and some present severe decline of systemic ventricular function. Intrinsic myocardial weakness, low heart rate response to exercise and diastolic filling impairment are discussed to be causative. Forty-nine long-term survivors with TGA (median age 23.7 year) after ABR were catheterized with measured oxygen consumption in four conditions (baseline, volume, atrial pacing, dobutamine) and the results were compared to 10 normal controls. Median cardiac output was significantly lower in the ABR group (2.2 vs. 2.6 l/min/m 2 ; p = 0.015), and systemic resistance was significantly elevated (28.9 vs. 22.2 U m 2 ; p = 0.04) in comparison with normals. While stroke volume rose by 27% in the control group, it dropped by 7% in patients after ABR at atrial pacing (80/min). Stroke volume increase after dobutamine was significantly lower after ABR in comparison with normal controls (34 vs. 106%; p = 0.001). Higher NYHA class (p = 0.043), degree of tricuspid regurgitation (p = 0.009) and ventricular function (p = 0.028) were associated with lower stroke volume increase. Limited exercise capability of patients after ABR for TGA is primarily due to limited diastolic filling of the ventricles due to stiff non-compliant atrial pathways. Elevated systemic resistance may lead to severe myocardial hypertrophy with possible ischemia and contribute to the multifactorial decline of ventricular function in some patients.

  5. Further characterization of the ABR gene in medulloblastoma

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

    Wright-White, E.C.; Haken, M.S. von; McDonald J.D.

    1994-09-01

    Although brain tumors are the most common type of solid cancer in children, little is known about their etiology at the molecular genetic level. Using a panel of 20 chromosome 17p markers, we have previously determined that loss of distal chromosome 17p DNA sequences occurs in 14 of 35 specimens (40%) of medulloblastoma, one of the most common pediatric intracranial neoplasms. Analysis of these same tumors using a PCR-denaturing gradient gel electrophoresis technique has shown only two p53 gene mutations. These results suggest that a tumor suppressor gene in addition to p53 may be located on distal chromosome 17p. Consensusmore » deletion mapping of our specimens suggests that the smallest site of chromosomal loss in defined distally by marker 144-D6, the most telomeric probe as yet identified on chromosome 17p, and proximally by the ABR marker, a BCR homologous gene containing two highly polymorphic VNTR regions. We have used fluorescence in situ hybridization and pulsed-field gel electrophoresis to determine that the ABR gene lies transcriptionally oriented 5{prime} to 3{prime} at a distance of 240 kb from marker 144-D6. We have also constructed a cosmid contig map spanning 120 kb of this region. Using one of these cosmids as a probe, we have detected breakpoints in three of the tumor specimens that lie between the two VNTR regions within the ABR gene. We have subsequently designed PCR primers to cover the breakpoint region which include the ABR exons which have the strongest homology to the BCR gene (Mbcr region), and are screening our tumor specimens for mutations. These results suggest that loss of ABR gene sequences may be involved in the etiology of medulloblastoma.« less

  6. Pharmacokinetics of Intranasal Scopolamine Gel Formulation During Antiorthostatic Bed Rest, a Microgravity Analog

    NASA Technical Reports Server (NTRS)

    Singh, Rajendra P.; Daniels, Vernie R.; Crady, Camille J.; Derendorf, H.; Putcha, L.

    2011-01-01

    Statement of Purpose, Innovation or Hypothesis: Space Motion sickness (SMS) is a long-standing problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is frequently used for the treatment of motion sickness (MS), and is available as transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability, thus allowing precise and reduced dosing in addition to offering rescue and treatment options. An intranasal gel dosage formulation of scopolamine (INSCOP) was developed and pharmacokinetics (PK) and bioavailability were determined in clinical trials with human subjects under IND guidelines.Description of Methods and Materials: The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostaticbed rest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 mg and 0.4 mg doses of INSCOP during AMB and ABR in a 4-way crossover design.Data and Results: Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose, Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration-versus-time curve (AUC) during ABR after the 0.4 mg dose.Interpretation, Conclusion or Significance: The difference in AUC and Cls at the higher (0.4 mg) but not the lower dose (0.2 mg) during ABR suggests that ABR may affect metabolism and/or clearance of INSCOP at higher doses . These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.

  7. Opportunities and challenges to improving antibiotic prescribing practices through a One Health approach: results of a comparative survey of doctors, dentists and veterinarians in Australia

    PubMed Central

    Zhuo, Annie; Norris, Jacqueline M; Gilbert, Gwendolyn L; Ward, Michael P; Bajorek, Beata V; Degeling, Chris; Rowbotham, Samantha J; Dawson, Angus; Nguyen, Ky-Anh; Hill-Cawthorne, Grant A; Sorrell, Tania C; Govendir, Merran; Kesson, Alison M; Iredell, Jonathan R

    2018-01-01

    Objectives To explore and compare the knowledge, attitudes and experiences of doctors, dentists and veterinarians (as prescribers) in relation to antibiotic use and antibiotic resistance (AbR), and to consider the implications of these for policy-making that support a One Health approach. Design A cross-sectional survey conducted online. Setting Doctors, dentists and veterinarians practising in primary, secondary or tertiary care in Australia. Participants 547 doctors, 380 dentists and 403 veterinarians completed the survey. Main outcome measures Prescribers’ knowledge, attitudes and perceptions of AbR, the extent to which a range of factors are perceived as barriers to appropriate prescribing practices, and perceived helpfulness of potential strategies to improve antibiotic prescribing in practice. Results There was substantial agreement across prescriber groups that action on AbR is required by multiple sectors and stakeholders. However, prescribers externalised responsibility to some extent by seeing the roles of others as more important than their own in relation to AbR. There were common and context-specific barriers to optimal prescribing across the prescriber groups. Prescriber groups generally perceived restrictive policies as unhelpful to supporting appropriate prescribing in their practice. Conclusions The results have implications for implementing a One Health approach that involves doctors, dentists and veterinarians as key players to tackling the crisis of AbR. The findings are that (1) prescribers understand and are likely receptive to a One Health policy approach to AbR, (2) policy development should be sensitive to barriers that are specific to individual prescriber groups and (3) the development and introduction of interventions that might be perceived as reducing prescriber autonomy will need to be carefully designed and implemented. PMID:29602857

  8. Amplification of ABA biosynthesis and signaling through a positive feedback mechanism in seeds.

    PubMed

    Nonogaki, Mariko; Sall, Khadidiatou; Nambara, Eiji; Nonogaki, Hiroyuki

    2014-05-01

    Abscisic acid is an essential hormone for seed dormancy. Our previous study using the plant gene switch system, a chemically induced gene expression system, demonstrated that induction of 9-cis-epoxycarotenoid dioxygenase (NCED), a rate-limiting ABA biosynthesis gene, was sufficient to suppress germination in imbibed Arabidopsis seeds. Here, we report development of an efficient experimental system that causes amplification of NCED expression during seed maturation. The system was created with a Triticum aestivum promoter containing ABA responsive elements (ABREs) and a Sorghum bicolor NCED to cause ABA-stimulated ABA biosynthesis and signaling, through a positive feedback mechanism. The chimeric gene pABRE:NCED enhanced NCED and ABF (ABRE-binding factor) expression in Arabidopsis Columbia-0 seeds, which caused 9- to 73-fold increases in ABA levels. The pABRE:NCED seeds exhibited unusually deep dormancy which lasted for more than 3 months. Interestingly, the amplified ABA pathways also caused enhanced expression of Arabidopsis NCED5, revealing the presence of positive feedback in the native system. These results demonstrated the robustness of positive feedback mechanisms and the significance of NCED expression, or single metabolic change, during seed maturation. The pABRE:NCED system provides an excellent experimental system producing dormant and non-dormant seeds of the same maternal origin, which differ only in zygotic ABA. The pABRE:NCED seeds contain a GFP marker which enables seed sorting between transgenic and null segregants and are ideal for comparative analysis. In addition to its utility in basic research, the system can also be applied to prevention of pre-harvest sprouting during crop production, and therefore contributes to translational biology. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  9. New insights into the characterization of Colletotrichum species associated with apple diseases in southern Brazil and Uruguay.

    PubMed

    Velho, Aline Cristina; Alaniz, Sandra; Casanova, Leticia; Mondino, Pedro; Stadnik, Marciel J

    2015-04-01

    Colletotrichum species are associated with Apple bitter rot (ABR) and Glomerella leaf spot (GLS). Whereas both apple diseases occur frequently in Brazil, only the former has been reported in Uruguay. This work was aimed at identifying and comparing morpho-cultural characteristics and pathogenic variability of thirty-nine Colletotrichum isolates from both countries. Sequencing of the internal transcribed spacer (ITS) rDNA, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and β-tubulin (TUB2) allowed the identification of three species causing ABR and GLS in Brazil, i.e., Colletotrichum fructicola, Colletotrichum karstii, and Colletotrichum nymphaeae; and three species causing ABR in Uruguay, i.e., C. fructicola, Colletotrichum theobromicola, and Colletotrichum melonis. Six groups of colony colours were recorded with group 1 (mycelium white to pink and in reverse pinkish) and group 2 (mycelium white to grey and in reverse pinkish) the most frequent. Isolates of C. fructicola and C. theobromicola were sensitive to benomyl, while C. karstii, C. nymphaeae, and C. melonis were resistant. Conidia were predominantly cylindrical for C. fructicola and C. karstii, fusiform for C. nymphaeae and C. melonis, and obclavate for C. theobromicola. Brazilian isolates caused ABR in wounded fruits, but only five in non-wounded ones. Uruguayan isolates produced symptoms in fruits with or without previous wounding. All Brazilian isolates from GLS and twelve from ABR were able to cause GLS symptoms, while a sole Uruguayan ABR-isolate caused leaf spot symptoms. This study gives a better insight on the new species causing apple disease in both countries and discusses their pathogenic potential. Copyright © 2014 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  10. Pharmacokinetics of Scopolamine Intranasal Gel Formulation (INSCOP) During Antiorthostatic Bedrest

    NASA Technical Reports Server (NTRS)

    Putcha, L.; Du, B.; Daniels, V.

    2010-01-01

    Space Motion Sickness (SMS) is experienced during early flight days of space missions and on reduced gravity simulation flights which require treatment with medications. Oral administration of scopolamine tablets is still a common practice to prevent SMS symptoms. Bioavailability of medications taken by mouth for SMS is often low and variable. Intranasal (IN) administration of medications has been reported to achieve higher and more reliable bioavailability than from an equivalent oral dose. In this FDA reviewed phase II clinical trial, we evaluated pharmacokinetics of an investigative new drug formulation, INSCOP during ambulatory (AMB) and antiorthostatic bedrest (HBR), a ground-based microgravity analog. Twelve subjects including 6 males and 6 females received 0.2 and 0.4 mg doses of INSCOP on separate days during AMB and ABR in a randomized, double blind cross over experimental design. Blood samples were collected at regular time intervals for 24 h post dose and analyzed for free scopolamine concentrations by an LC-MS-MS method. Pharmacokinetic parameters were calculated using concentration versus time data and compared between AMB and ABR conditions. Results indicated that maximum concentration and relative bioavailability increased marginally during ABR compared to AMB; differences in PK parameters between AMB and ABR were greater with 0.2 mg than with 0.4 mg dose. Gender specific differences in PK parameters was observed both during AMB and ABR with differences higher in females between the two conditions than in males. A significant observation is that while gender differences in PK appear to exist, the differences in primary PK parameters between AMB and ABR after IN administration, unlike oral administration, are minimal and may not be clinically significant for both genders.

  11. Spatial and temporal variation in the community prevalence of antibiotic resistance in Bangladesh: an integrated surveillance study protocol

    PubMed Central

    Unicomb, Leanne; Wood, Paul; Smith, Michael; Asaduzzaman, Muhammad; Islam, Mohammad Aminul

    2018-01-01

    Introduction Increasing antibiotic resistance (ABR) in low-income and middle-income countries such as Bangladesh presents a major health threat. However, assessing the scale of the health risk is problematic in the absence of reliable data on the community prevalence of antibiotic-resistant bacteria. We describe the protocol for a small-scale integrated surveillance programme that aims to quantify the prevalence of colonisation with antibiotic-resistant bacteria and concentrations of antibiotic-resistant genes from a ‘One Health’ perspective. The holistic assessment of ABR in humans, animals and within the environment in urban and rural Bangladesh will generate comprehensive data to inform human health risk. Methods and analysis The study design focuses on three exposure-relevant sites where there is enhanced potential for transmission of ABR between humans, animals and the environment: (1) rural poultry-owning households, (2) commercial poultry farms and (3) urban live-bird markets. The comparison of ABR prevalence in human groups with high and low exposure to farming and poultry will enable us to test the hypothesis that ABR bacteria and genes from the environment and food-producing animals are potential sources of transmission to humans. Escherichia coli is used as an ABR indicator organism due to its widespread environmental presence and colonisation in both the human and animal gastrointestinal tract. Ethics and dissemination The study has been approved by the Institutional Review Board of the International Centre for Diarrhoeal Disease Research, Bangladesh, and Loughborough University Ethics Committee. Data for the project will be stored on the open access repository of the Centre for Ecology and Hydrology, Natural Environment Research Council. The results of this study will be published in peer-reviewed journals and presented at national and international conferences. PMID:29705771

  12. Relating the variability of tone-burst otoacoustic emission and auditory brainstem response latencies to the underlying cochlear mechanics

    NASA Astrophysics Data System (ADS)

    Verhulst, Sarah; Shera, Christopher A.

    2015-12-01

    Forward and reverse cochlear latency and its relation to the frequency tuning of the auditory filters can be assessed using tone bursts (TBs). Otoacoustic emissions (TBOAEs) estimate the cochlear roundtrip time, while auditory brainstem responses (ABRs) to the same stimuli aim at measuring the auditory filter buildup time. Latency ratios are generally close to two and controversy exists about the relationship of this ratio to cochlear mechanics. We explored why the two methods provide different estimates of filter buildup time, and ratios with large inter-subject variability, using a time-domain model for OAEs and ABRs. We compared latencies for twenty models, in which all parameters but the cochlear irregularities responsible for reflection-source OAEs were identical, and found that TBOAE latencies were much more variable than ABR latencies. Multiple reflection-sources generated within the evoking stimulus bandwidth were found to shape the TBOAE envelope and complicate the interpretation of TBOAE latency and TBOAE/ABR ratios in terms of auditory filter tuning.

  13. The auditory brain-stem response to complex sounds: a potential biomarker for guiding treatment of psychosis.

    PubMed

    Tarasenko, Melissa A; Swerdlow, Neal R; Makeig, Scott; Braff, David L; Light, Gregory A

    2014-01-01

    Cognitive deficits limit psychosocial functioning in schizophrenia. For many patients, cognitive remediation approaches have yielded encouraging results. Nevertheless, therapeutic response is variable, and outcome studies consistently identify individuals who respond minimally to these interventions. Biomarkers that can assist in identifying patients likely to benefit from particular forms of cognitive remediation are needed. Here, we describe an event-related potential (ERP) biomarker - the auditory brain-stem response (ABR) to complex sounds (cABR) - that appears to be particularly well-suited for predicting response to at least one form of cognitive remediation that targets auditory information processing. Uniquely, the cABR quantifies the fidelity of sound encoded at the level of the brainstem and midbrain. This ERP biomarker has revealed auditory processing abnormalities in various neurodevelopmental disorders, correlates with functioning across several cognitive domains, and appears to be responsive to targeted auditory training. We present preliminary cABR data from 18 schizophrenia patients and propose further investigation of this biomarker for predicting and tracking response to cognitive interventions.

  14. The Effects of a Home-Based Connective Tissue Targeting Therapy on Hip Development in Children With Cerebral Palsy: Six Case Reports.

    PubMed

    Drewes, Erika; Driscoll, Mark; Blyum, Leonid; Vincentz, Diane

    2016-01-01

    Hip subluxation in children with Cerebral Palsy (CP) has an incidence of 10-30 %, and children with severe CP having the highest incidence. The condition deteriorates if left untreated. Surgery is the most common method used in managing hip subluxation because standard conservative therapies do not improve it. Surgery may have to be repeated and comes at a biological cost to the child. A new home-based CAM, Advanced Biomechanical Rehabilitation (ABR), has shown encouraging results leading to improved spinal stability and stability in sitting in children with severe CP. This case report examines hip development over time in six children with severe CP in the ABR Program. Changes in their clinical picture and pelvic X-Rays are reported. ABR appeared to help stabilize and improve hip subluxation, resulting in these children not requiring further surgical intervention. These findings warrant further investigation of ABR as a noninvasive therapy for hip subluxation. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. A kernel-based novelty detection scheme for the ultra-fast detection of chirp evoked Auditory Brainstem Responses.

    PubMed

    Corona-Strauss, Farah I; Delb, Wolfgang; Schick, Bernhard; Strauss, Daniel J

    2010-01-01

    Auditory Brainstem Responses (ABRs) are used as objective method for diagnostics and quantification of hearing loss. Many methods for automatic recognition of ABRs have been developed, but none of them include the individual measurement setup in the analysis. The purpose of this work was to design a fast recognition scheme for chirp-evoked ABRs that is adjusted to the individual measurement condition using spontaneous electroencephalographic activity (SA). For the classification, the kernel-based novelty detection scheme used features based on the inter-sweep instantaneous phase synchronization as well as energy and entropy relations in the time-frequency domain. This method provided SA discrimination from stimulations above the hearing threshold with a minimum number of sweeps, i.e., 200 individual responses. It is concluded that the proposed paradigm, processing procedures and stimulation techniques improve the detection of ABRs in terms of the degree of objectivity, i.e., automation of procedure, and measurement time.

  16. [Does co-operation research provide approaches to explain the changes in the German hospital market?].

    PubMed

    Raible, C; Leidl, R

    2004-11-01

    The German hospital market faces an extensive process of consolidation. In this change hospitals consider cooperation as one possibility to improve competitiveness. To investigate explanations of changes in the German hospital market by theoretical approaches of cooperation research. The aims and mechanism of the theories, their relevance in terms of contents and their potential for empirical tests were used as criteria to assess the approaches, with current and future trends in the German hospital market providing the framework. Based on literature review, six theoretical approaches were investigated: industrial organization, transaction cost theory, game theory, resource dependency, institutional theory, and co-operative investment and finance theory. In addition, the data needed to empirically test the theories were specified. As a general problem, some of the theoretical approaches set a perfect market as a precondition. This precondition is not met by the heavily regulated German hospital market. Given the current regulations and the assessment criteria, industrial organization as well as resource-dependency and institutional theory approaches showed the highest potential to explain various aspects of the changes in the hospital market. So far, none of the approaches investigated provides a comprehensive and empirically tested explanation of the changes in the German hospital market. However, some of the approaches provide a theoretical background for part of the changes. As this dynamic market is economically of high significance, there is a need for further development and empirical testing of relevant theoretical approaches.

  17. [Effects of sildenafil citrate on mice hearing].

    PubMed

    Luo, Xiaoqin; Guo, Xuyao; Chen, Lin; Chen, Xiaohong; Zhang, Xueyuan; Yuan, Wei

    2014-06-01

    The purpose of this investigation was to study the effects of the Sildenafil citrate on mice hearing. Seven-week-old adult male Kunming mice were used. The mice were randomly divided into four groups with 10 mice in each group.Sildenafil groups were orally administered daily with sildenafil [0.1 mg/(kg·d), 1 mg/(kg·d), 10 mg/(kg·d)] and control group was orally administered with normal saline. Then mice were tested for auditory brainstem response (ABR) to observe the changes of ABR's thresholds at before administration and 1, 5, 10, 15, 20 day afterwards. The mice basilar membrane samples were studied by immunofluorescent labeling.High performance liquid chromatography was used for determination the concentration of sildenafil in endolymph of mice cochlea. Statistical analysis was performed using SPSS 13.0. After 30 min following administration, the Sildenafil in endolymph of mice cochlear could be assayed by high performance liquid chromatography, and it was dose-related.Sildenafil increased the hearing thresholds with the time of administration. Hearing thresholds increased significantly in the sildenafil group at 20 d compared to the control group (P < 0.05). After administered high dose of Sildenafil, on the 20th day, the ABR thresholds average threshold was (60.0 ± 10.0) dBnHL, and the control group was (14.5 ± 6.0) dBnHL.Hair cells damages in the base ring of cochlea could be observed in experimental group in a concentration-dependent manner. Sildenafil can pass through blood-labyrinth barrier to the inner ear, and doses of sildenafil administration can induce hearing impairment in mice.

  18. Auditory Brainstem Responses in Childhood Psychosis.

    ERIC Educational Resources Information Center

    Gillberg, Christopher; And Others

    1983-01-01

    Auditory brainstem responses (ABR) were compared in 24 autistic children, seven children with other childhood psychoses, and 31 normal children. One-third of the autistic Ss showed abnormal ABR indicating brainstem dysfunction and correlating with muscular hypotonia and severe language impairment. Ss with other psychoses and normal Ss showed…

  19. Cooperative DNA Recognition Modulated by an Interplay between Protein-Protein Interactions and DNA-Mediated Allostery

    PubMed Central

    Merino, Felipe; Bouvier, Benjamin; Cojocaru, Vlad

    2015-01-01

    Highly specific transcriptional regulation depends on the cooperative association of transcription factors into enhanceosomes. Usually, their DNA-binding cooperativity originates from either direct interactions or DNA-mediated allostery. Here, we performed unbiased molecular simulations followed by simulations of protein-DNA unbinding and free energy profiling to study the cooperative DNA recognition by OCT4 and SOX2, key components of enhanceosomes in pluripotent cells. We found that SOX2 influences the orientation and dynamics of the DNA-bound configuration of OCT4. In addition SOX2 modifies the unbinding free energy profiles of both DNA-binding domains of OCT4, the POU specific and POU homeodomain, despite interacting directly only with the first. Thus, we demonstrate that the OCT4-SOX2 cooperativity is modulated by an interplay between protein-protein interactions and DNA-mediated allostery. Further, we estimated the change in OCT4-DNA binding free energy due to the cooperativity with SOX2, observed a good agreement with experimental measurements, and found that SOX2 affects the relative DNA-binding strength of the two OCT4 domains. Based on these findings, we propose that available interaction partners in different biological contexts modulate the DNA exploration routes of multi-domain transcription factors such as OCT4. We consider the OCT4-SOX2 cooperativity as a paradigm of how specificity of transcriptional regulation is achieved through concerted modulation of protein-DNA recognition by different types of interactions. PMID:26067358

  20. Cooperative DNA Recognition Modulated by an Interplay between Protein-Protein Interactions and DNA-Mediated Allostery.

    PubMed

    Merino, Felipe; Bouvier, Benjamin; Cojocaru, Vlad

    2015-06-01

    Highly specific transcriptional regulation depends on the cooperative association of transcription factors into enhanceosomes. Usually, their DNA-binding cooperativity originates from either direct interactions or DNA-mediated allostery. Here, we performed unbiased molecular simulations followed by simulations of protein-DNA unbinding and free energy profiling to study the cooperative DNA recognition by OCT4 and SOX2, key components of enhanceosomes in pluripotent cells. We found that SOX2 influences the orientation and dynamics of the DNA-bound configuration of OCT4. In addition SOX2 modifies the unbinding free energy profiles of both DNA-binding domains of OCT4, the POU specific and POU homeodomain, despite interacting directly only with the first. Thus, we demonstrate that the OCT4-SOX2 cooperativity is modulated by an interplay between protein-protein interactions and DNA-mediated allostery. Further, we estimated the change in OCT4-DNA binding free energy due to the cooperativity with SOX2, observed a good agreement with experimental measurements, and found that SOX2 affects the relative DNA-binding strength of the two OCT4 domains. Based on these findings, we propose that available interaction partners in different biological contexts modulate the DNA exploration routes of multi-domain transcription factors such as OCT4. We consider the OCT4-SOX2 cooperativity as a paradigm of how specificity of transcriptional regulation is achieved through concerted modulation of protein-DNA recognition by different types of interactions.

  1. Lead exposure results in hearing loss and disruption of the cochlear blood-labyrinth barrier and the protective role of iron supplement.

    PubMed

    Liu, Xinqin; Zheng, Gang; Wu, Yongxiang; Shen, Xuefeng; Jing, Jinfei; Yu, Tao; Song, Han; Chen, Jingyuan; Luo, Wenjing

    2013-12-01

    This study was designed to investigate the impact of lead (Pb(2+)) on the auditory system and its molecular mechanisms. Pb(AC)2 was administrated to male SD rats aged 21-22 d for 8 weeks at a dose of 300ppm. Male guinea pigs were also administrated with 50mg/kg Pb(AC)2 two times a week for 8 weeks. The auditory nerve-brainstem evoked responses (ABR) was recorded and the morphological changes of the outer hair cells (OHCs) were observed with Phallodin-FITC staining. In addition, the integrity of the blood-labyrinth barrier was observed by TEM and the expression of tight junction proteins (TJPs) in the cochlear stria vascularis was determined by immunofluorescence. Our results showed that Pb(2+) exposure resulted in increased ABR threshold in both rats and guinea pigs. Abnormal shapes and loss of OHCs were found in the cochlear basilar membrane following the Pb(2+) exposure. TEM study showed that the tight junctions between the endothelial cells and the border cells were lost and disrupted. Down-regulation of the occludin, ZO-1 and claudin-5 in the stria vascularis suggested that the increased permeability of the blood-labyrinth barrier may attribute to the Pb(2+)-induced decrease of TJPs' expression. Additionally, Fe(2+) supplement partly reversed the Pb(2+)-induced hearing loss and down-regulation of TJPs. Taken together, these data indicate that the disruption of blood-labyrinth barrier by down-regulating the expression of TJPs plays a role in the Pb(2+)-induced hearing loss, and Fe(2+) supplement protects the auditory system against Pb(2+)-induced toxicity and may have significant clinical implications. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Influence of two-electrode montages on the level-specific (LS) CE-Chirp auditory brainstem response (ABR) at multiple intensity levels.

    PubMed

    Dzulkarnain, Ahmad Aidil Arafat; Noor Ibrahim, Siti Hajra Mu'minah; Anuar, Nur Farah Aida; Abdullah, Siti Aisyah; Tengku Zam Zam, Tengku Zulaila Hasma; Rahmat, Sarah; Mohd Ruzai, Muhammad Amar

    2017-10-01

    To investigate the influence of two different electrode montages (ipsilateral: reference to mastoid and vertical: reference to nape of neck) to the ABR results recorded using a level-specific (LS)-CE-Chirp® in normally hearing subjects at multiple intensities levels. Quasi-experimental and repeated measure study designs were applied in this study. Two different stopping criteria were used, (1) a fixed-signal averaging 4000 sweeps and, (2) a minimum quality indicator of Fmp = 3.1 with a minimum of 800 sweeps. Twenty-nine normally hearing adults (18 females, 11 male) participated. Wave V amplitudes were significantly larger in the LS CE-Chirp® recorded from the vertical montage than the ipsilateral montage. Waves I and III amplitudes were significantly larger from the ipsilateral LS CE-Chirp® than from the other montages and stimulus combinations. The differences in the quality of the ABR recording between the vertical and ipsilateral montages were marginal. Overall, the result suggested that the vertical LS CE-Chirp® ABR had a high potential for a threshold-seeking application, because it produced a higher wave V amplitude. The Ipsilateral LS CE-Chirp® ABR, on the other hand, might also have a high potential for the site of lesion application, because it produced larger waves I and III amplitudes.

  3. Protective Effects of α-Tocopherol on ABR Threshold Shift in Rabbits Exposed to Noise and Carbon Monoxide.

    PubMed

    Motallebi Kashani, Masoud; Mortazavi, Seyyed Bagher; Khavanin, Ali; Allameh, Abdolamir; Mirzaee, Ramezan; Akbari, Mehdi

    2011-01-01

    Noise induced hearin gloss (NIHL) is one of the most important occupational disease world wide. NIHL has been found potentiate by simultaneous carbon monoxide (CO) exposure. Free radicals have been implicated in cochlear damage resulted from the exposure to noise and due to the CO hypoxia. This study examined whether α-tocopherol administration , as a free radical scavenger, causes the attenuation of auditory brainstem response (ABR) threshold shifts resulting from noise exposure and noise plus CO exposure. Forty-two rabbits were divided in to seven groups including control, noise + saline, noise + CO + saline, noise + α-tocopherol, noise + CO + α-tocopherol , CO + α-tocopherol and α-tocopherol alone. ABR was assessed before exposure, 1 hand 14 days post exposure. The administration of 50 mg/Kg of α-tocopherol prior, following and post exposure to noise or noise plus CO recovered permanent ABR threshold shift at 1 and KHz almost to the baseline and provided significant attenuation in permanent ABR threshold shift at 4 and 8 KHz in subject swhich were exposed to noise but it did not block the potentiating of threshold elevation by CO exposure (extra threshold loss by combined exposure) at 4 and 8 KHz. α Tocopherol provides protective effect against the hearing loss resulting from noise exposure and simultaneous exposure to noise plus CO.

  4. Impact of mild traumatic brain injury on auditory brain stem dysfunction in mouse model.

    PubMed

    Amanipour, Reza M; Frisina, Robert D; Cresoe, Samantha A; Parsons, Teresa J; Xiaoxia Zhu; Borlongan, Cesario V; Walton, Joseph P

    2016-08-01

    The auditory brainstem response (ABR) is an electrophysiological test that examines the functionality of the auditory nerve and brainstem. Traumatic brain injury (TBI) can be detected if prolonged peak latency is observed in ABR measurements, since latency measures the neural conduction time in the brainstem, and an increase in latency can be a sign of pathological lesion at the auditory brainstem level. The ABR is elicited by brief sounds that can be used to measure hearing sensitivity as well as temporal processing. Reduction in peak amplitudes and increases in latency are indicative of dysfunction in the auditory nerve and/or central auditory pathways. In this study we used sixteen young adult mice that were divided into two groups: sham and mild traumatic brain injury (mTBI), with ABR measurements obtained prior to, and at 2, 6, and 14 weeks after injury. Abnormal ABRs were observed for the nine TBI cases as early as two weeks after injury and the deficits lasted for fourteen weeks after injury. Results indicated a significant reduction in the Peak 1 (P1) and Peak 4 (P4) amplitudes to the first noise burst, as well as an increase in latency response for P1 and P4 following mTBI. These results are the first to demonstrate auditory sound processing deficits in a rodent model of mild TBI.

  5. Test-retest reliability of speech-evoked auditory brainstem response in healthy children at a low sensation level.

    PubMed

    Zakaria, Mohd Normani; Jalaei, Bahram

    2017-11-01

    Auditory brainstem responses evoked by complex stimuli such as speech syllables have been studied in normal subjects and subjects with compromised auditory functions. The stability of speech-evoked auditory brainstem response (speech-ABR) when tested over time has been reported but the literature is limited. The present study was carried out to determine the test-retest reliability of speech-ABR in healthy children at a low sensation level. Seventeen healthy children (6 boys, 11 girls) aged from 5 to 9 years (mean = 6.8 ± 3.3 years) were tested in two sessions separated by a 3-month period. The stimulus used was a 40-ms syllable /da/ presented at 30 dB sensation level. As revealed by pair t-test and intra-class correlation (ICC) analyses, peak latencies, peak amplitudes and composite onset measures of speech-ABR were found to be highly replicable. Compared to other parameters, higher ICC values were noted for peak latencies of speech-ABR. The present study was the first to report the test-retest reliability of speech-ABR recorded at low stimulation levels in healthy children. Due to its good stability, it can be used as an objective indicator for assessing the effectiveness of auditory rehabilitation in hearing-impaired children in future studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Effects of noise exposure on neonatal auditory brainstem response thresholds in pregnant guinea pigs at different gestational periods.

    PubMed

    Morimoto, Chihiro; Nario, Kazuhiko; Nishimura, Tadashi; Shimokura, Ryota; Hosoi, Hiroshi; Kitahara, Tadashi

    2017-01-01

    Noise exposure during pregnancy has been reported to cause fetal hearing impairment. However, little is known about the effects of noise exposure during various gestational stages on postnatal hearing. In the present study, we investigated the effects of noise exposure on auditory brainstem response (ABR) at the early, mid-, and late gestational periods in newborn guinea pigs. Pregnant guinea pigs were exposed to 4-kHz pure tone at a 120-dB sound pressure level for 4 h. We divided the animals into four groups as follows: the control, early gestational exposure, mid-gestational exposure, and late gestational exposure groups. ABR thresholds and latencies in newborns were recorded using 1-, 2-, and 4-kHz tone burst on postnatal days 1, 7, 14, and 28. Changes in ABR thresholds and latencies were measured between the 4 × 4 and 4 × 3 factorial groups mentioned above (gestational periods × postnatal days, gestational periods × frequencies). The thresholds were low in the order of control group < early gestational exposure group < mid-gestational exposure group and late gestational exposure group. Noise exposure during pregnancy influenced ABR thresholds in neonatal guinea pigs. This is the first study to show that noise exposure during the early, mid-, and late gestational periods significantly elevated ABR thresholds in neonatal guinea pigs. © 2016 Japan Society of Obstetrics and Gynecology.

  7. Modulation of oxidative responses by a virulent isolate of Colletotrichum fructicola in apple leaves.

    PubMed

    Velho, Aline Cristina; Rockenbach, Mathias F; Mondino, Pedro; Stadnik, Marciel J

    2016-10-01

    Apple bitter rot (ABR) and Glomerella leaf spot (GLS) can be caused by Colletotrichum fructicola. Although both diseases can occur simultaneously in orchards, some isolates show clear organ specialization. Thus, this work was aimed to compare microscopically the development of preinfective structures of ABR- and GLS isolates and their impact on the enzymatic oxidant defense system during the leaf infection process. On leaves, conidial germlings of GLS-isolate formed appressoria mostly sessile. In contrast, those of ABR-isolate were pedicellate and formed multiple melanized appressoria probably as a sign of unsuccessful infection attempts. Neither ABR- nor GLS isolate triggered hypersensitive response in apple leaves. In overall, the activity of scavenging enzymes was higher and long-lasting in leaves inoculated by GLS- than by ABR isolate and control. Guaiacol peroxidase, catalase, and glutathione reductase had activity peaks within 24 h after inoculation (HAI). Ascorbate peroxidase activity was higher only in GLS-infected leaves at 6 HAI, while superoxide dismutase remained unaltered. A lower level of hydrogen peroxide (H2O2) was determined in GLS-infected plants at 48 HAI, but the electrolyte leakage markedly increased. Disease symptoms in leaves were only caused by GLS-isolate. Results suggest that the virulent isolate coordinately downregulates the oxidative plant defense responses enabling its successful establishment in apple leaves. Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  8. Abscisic Acid and abiotic stress signaling.

    PubMed

    Tuteja, Narendra

    2007-05-01

    Abiotic stress is severe environmental stress, which impairs crop production on irrigated land worldwide. Overall, the susceptibility or tolerance to the stress in plants is a coordinated action of multiple stress responsive genes, which also cross-talk with other components of stress signal transduction pathways. Plant responses to abiotic stress can be determined by the severity of the stress and by the metabolic status of the plant. Abscisic acid (ABA) is a phytohormone critical for plant growth and development and plays an important role in integrating various stress signals and controlling downstream stress responses. Plants have to adjust ABA levels constantly in responce to changing physiological and environmental conditions. To date, the mechanisms for fine-tuning of ABA levels remain elusive. The mechanisms by which plants respond to stress include both ABA-dependent and ABA-independent processes. Various transcription factors such as DREB2A/2B, AREB1, RD22BP1 and MYC/MYB are known to regulate the ABA-responsive gene expression through interacting with their corrosponding cis-acting elements such as DRE/CRT, ABRE and MYCRS/MYBRS, respectively. Understanding these mechanisms is important to improve stress tolerance in crops plants. This article first describes the general pathway for plant stress response followed by roles of ABA and transcription factors in stress tolerance including the regulation of ABA biosynthesis.

  9. Abscisic Acid and Abiotic Stress Signaling

    PubMed Central

    2007-01-01

    Abiotic stress is severe environmental stress, which impairs crop production on irrigated land worldwide. Overall, the susceptibility or tolerance to the stress in plants is a coordinated action of multiple stress responsive genes, which also cross-talk with other components of stress signal transduction pathways. Plant responses to abiotic stress can be determined by the severity of the stress and by the metabolic status of the plant. Abscisic acid (ABA) is a phytohormone critical for plant growth and development and plays an important role in integrating various stress signals and controlling downstream stress responses. Plants have to adjust ABA levels constantly in responce to changing physiological and environmental conditions. To date, the mechanisms for fine-tuning of ABA levels remain elusive. The mechanisms by which plants respond to stress include both ABA-dependent and ABA-independent processes. Various transcription factors such as DREB2A/2B, AREB1, RD22BP1 and MYC/MYB are known to regulate the ABA-responsive gene expression through interacting with their corrosponding cis-acting elements such as DRE/CRT, ABRE and MYCRS/MYBRS, respectively. Understanding these mechanisms is important to improve stress tolerance in crops plants. This article first describes the general pathway for plant stress response followed by roles of ABA and transcription factors in stress tolerance including the regulation of ABA biosynthesis. PMID:19516981

  10. A novel mechanism of functional cooperativity regulation by thiol redox status in a dimeric inorganic pyrophosphatase.

    PubMed

    Costa, Evenilton P; Façanha, Arnoldo R; Cruz, Criscila S; Silva, Jhenifer N; Machado, Josias A; Carvalho, Gabriel M; Fernandes, Mariana R; Martins, Renato; Campos, Eldo; Romeiro, Nelilma C; Githaka, Naftaly W; Konnai, Satoru; Ohashi, Kazuhiko; Vaz, Itabajara S; Logullo, Carlos

    2017-01-01

    Inorganic PPases are essential metal-dependent enzymes that convert pyrophosphate into orthophosphate. This reaction is quite exergonic and provides a thermodynamic advantage for many ATP-driven biosynthetic reactions. We have previously demonstrated that cytosolic PPase from R. microplus embryos is an atypical Family I PPase. Here, we explored the functional role of the cysteine residues located at the homodimer interface, its redox sensitivity, as well as structural and kinetic parameters related to thiol redox status. In this work, we used prokaryotic expression system for recombinant protein overexpression, biochemical approaches to assess kinetic parameters, ticks embryos and computational approaches to analyze and predict critical amino acids as well as physicochemical properties at the homodimer interface. Cysteine 339, located at the homodimer interface, was found to play an important role in stabilizing a functional cooperativity between the two catalytic sites, as indicated by kinetics and Hill coefficient analyses of the WT-rBmPPase. WT-rBmPPase activity was up-regulated by physiological antioxidant molecules such as reduced glutathione and ascorbic acid. On the other hand, hydrogen peroxide at physiological concentrations decreased the affinity of WT-rBmPPase for its substrate (PP i ), probably by inducing disulfide bridge formation. Our results provide a new angle in understanding redox control by disulfide bonds formation in enzymes from hematophagous arthropods. The reversibility of the down-regulation is dependent on hydrophobic interactions at the dimer interface. This study is the first report on a soluble PPase where dimeric cooperativity is regulated by a redox mechanism, according to cysteine redox status. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Self-Regulation, Cooperative Learning, and Academic Self-Efficacy: Interactions to Prevent School Failure

    PubMed Central

    Fernandez-Rio, Javier; Cecchini, Jose A.; Méndez-Gimenez, Antonio; Mendez-Alonso, David; Prieto, Jose A.

    2017-01-01

    Learning to learn and learning to cooperate are two important goals for individuals. Moreover, self regulation has been identified as fundamental to prevent school failure. The goal of the present study was to assess the interactions between self-regulated learning, cooperative learning and academic self-efficacy in secondary education students experiencing cooperative learning as the main pedagogical approach for at least one school year. 2.513 secondary education students (1.308 males, 1.205 females), 12–17 years old (M = 13.85, SD = 1.29), enrolled in 17 different schools belonging to the National Network of Schools on Cooperative Learning in Spain agreed to participate. They all had experienced this pedagogical approach a minimum of one school year. Participants were asked to complete the cooperative learning questionnaire, the strategies to control the study questionnaire and the global academic self-efficacy questionnaire. Participants were grouped based on their perceptions on cooperative learning and self-regulated learning in their classes. A combination of hierarchical and κ-means cluster analyses was used. Results revealed a four-cluster solution: cluster one included students with low levels of cooperative learning, self-regulated learning and academic self-efficacy, cluster two included students with high levels of cooperative learning, self-regulated learning and academic self-efficacy, cluster three included students with high levels of cooperative learning, low levels of self-regulated learning and intermediate-low levels of academic self-efficacy, and, finally, cluster four included students with high levels of self-regulated learning, low levels of cooperative learning, and intermediate-high levels of academic self-efficacy. Self-regulated learning was found more influential than cooperative learning on students’ academic self-efficacy. In cooperative learning contexts students interact through different types of regulations: self, co, and shared. Educators should be aware of these interactions, symmetrical or asymmetrical, because they determine the quality and quantity of the students’ participation and achievements, and they are key elements to prevent school failure. PMID:28154544

  12. Self-Regulation, Cooperative Learning, and Academic Self-Efficacy: Interactions to Prevent School Failure.

    PubMed

    Fernandez-Rio, Javier; Cecchini, Jose A; Méndez-Gimenez, Antonio; Mendez-Alonso, David; Prieto, Jose A

    2017-01-01

    Learning to learn and learning to cooperate are two important goals for individuals. Moreover, self regulation has been identified as fundamental to prevent school failure. The goal of the present study was to assess the interactions between self-regulated learning, cooperative learning and academic self-efficacy in secondary education students experiencing cooperative learning as the main pedagogical approach for at least one school year. 2.513 secondary education students (1.308 males, 1.205 females), 12-17 years old ( M = 13.85, SD = 1.29), enrolled in 17 different schools belonging to the National Network of Schools on Cooperative Learning in Spain agreed to participate. They all had experienced this pedagogical approach a minimum of one school year. Participants were asked to complete the cooperative learning questionnaire, the strategies to control the study questionnaire and the global academic self-efficacy questionnaire. Participants were grouped based on their perceptions on cooperative learning and self-regulated learning in their classes. A combination of hierarchical and κ -means cluster analyses was used. Results revealed a four-cluster solution: cluster one included students with low levels of cooperative learning, self-regulated learning and academic self-efficacy, cluster two included students with high levels of cooperative learning, self-regulated learning and academic self-efficacy, cluster three included students with high levels of cooperative learning, low levels of self-regulated learning and intermediate-low levels of academic self-efficacy, and, finally, cluster four included students with high levels of self-regulated learning, low levels of cooperative learning, and intermediate-high levels of academic self-efficacy. Self-regulated learning was found more influential than cooperative learning on students' academic self-efficacy. In cooperative learning contexts students interact through different types of regulations: self, co, and shared. Educators should be aware of these interactions, symmetrical or asymmetrical, because they determine the quality and quantity of the students' participation and achievements, and they are key elements to prevent school failure.

  13. Neonatal Auditory Brainstem Responses Recorded from Four Electrode Montages.

    ERIC Educational Resources Information Center

    Stuart, Andrew; And Others

    1996-01-01

    Simultaneous auditory brainstem responses (ABRs) to click stimuli at 30 and 60 decibels were recorded from 16 full-term neonates with 4 different electrode arrays. Results indicated that ABR waveforms were morphologically similar to those recorded in adults. Waveform expression was variable with different electrode recording montages. (Author/DB)

  14. Auditory Brainstem Responses in Autism: Brainstem Dysfunction or Peripheral Hearing Loss?

    ERIC Educational Resources Information Center

    Klin, Ami

    1993-01-01

    A review of 11 studies of auditory brainstem response (ABR) in individuals with autism concludes that the ABR data are only suggestive (rather than supportive) of brainstem involvement in autism. The presence of peripheral hearing impairment was observed in some of the autistic individuals. (Author/DB)

  15. Teaching the Adult Beginning Reader: Designing Research Based Reading Instructional Strategies.

    ERIC Educational Resources Information Center

    Boraks, Nancy; Richardson, Judy

    Acknowledging that while it is difficult to suggest specific instructional strategies for accommodating differing adult beginning readers' (ABR) psychosocial behavior, this paper offers appropriate instructional principles based on the educational and social needs of the ABR. The principles presented are as follows: (1) teachers should help adults…

  16. 24 CFR 135.72 - Cooperation in achieving compliance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... regulations in this part. The provisions of 2 CFR part 2424 apply to the employment, engagement of services... EMPLOYMENT AND BUSINESS OPPORTUNITY ECONOMIC OPPORTUNITIES FOR LOW- AND VERY LOW-INCOME PERSONS Complaint and... to apply for jobs and to bid for contracts generated by covered HUD financial assistance depends upon...

  17. Detecting cis-regulatory binding sites for cooperatively binding proteins

    PubMed Central

    van Oeffelen, Liesbeth; Cornelis, Pierre; Van Delm, Wouter; De Ridder, Fedor; De Moor, Bart; Moreau, Yves

    2008-01-01

    Several methods are available to predict cis-regulatory modules in DNA based on position weight matrices. However, the performance of these methods generally depends on a number of additional parameters that cannot be derived from sequences and are difficult to estimate because they have no physical meaning. As the best way to detect cis-regulatory modules is the way in which the proteins recognize them, we developed a new scoring method that utilizes the underlying physical binding model. This method requires no additional parameter to account for multiple binding sites; and the only necessary parameters to model homotypic cooperative interactions are the distances between adjacent protein binding sites in basepairs, and the corresponding cooperative binding constants. The heterotypic cooperative binding model requires one more parameter per cooperatively binding protein, which is the concentration multiplied by the partition function of this protein. In a case study on the bacterial ferric uptake regulator, we show that our scoring method for homotypic cooperatively binding proteins significantly outperforms other PWM-based methods where biophysical cooperativity is not taken into account. PMID:18400778

  18. An A257V Mutation in the Bacillus subtilis Response Regulator Spo0A Prevents Regulated Expression of Promoters with Low-Consensus Binding Sites▿

    PubMed Central

    Seredick, Steve D.; Seredick, Barbara M.; Baker, David; Spiegelman, George B.

    2009-01-01

    In Bacillus species, the master regulator of sporulation is Spo0A. Spo0A functions by both activating and repressing transcription initiation from target promoters that contain 0A boxes, the binding sites for Spo0A. Several classes of spo0A mutants have been isolated, and the molecular basis for their phenotypes has been determined. However, the molecular basis of the Spo0A(A257V) substitution, representative of an unusual phenotypic class, is not understood. Spo0A(A257V) is unusual in that it abolishes sporulation; in vivo, it fails to activate transcription from key stage II promoters yet retains the ability to repress the abrB promoter. To determine how Spo0A(A257V) retains the ability to repress but not stimulate transcription, we performed a series of in vitro and in vivo assays. We found unexpectedly that the mutant protein both stimulated transcription from the spoIIG promoter and repressed transcription from the abrB promoter, albeit twofold less than the wild type. A DNA binding analysis of Spo0A(A257V) showed that the mutant protein was less able to tolerate alterations in the sequence and arrangement of its DNA binding sites than the wild-type protein. In addition, we found that Spo0A(A257V) could stimulate transcription of a mutant spoIIG promoter in vivo in which low-consensus binding sites were replaced by high-consensus binding sites. We conclude that Spo0A(A257V) is able to bind to and regulate the expression of only genes whose promoters contain high-consensus binding sites and that this effect is sufficient to explain the observed sporulation defect. PMID:19581368

  19. Arterial baroreflex control of sympathetic nerve activity during acute hypotension: effect of fitness

    NASA Technical Reports Server (NTRS)

    Fadel, P. J.; Stromstad, M.; Hansen, J.; Sander, M.; Horn, K.; Ogoh, S.; Smith, M. L.; Secher, N. H.; Raven, P. B.

    2001-01-01

    We examined arterial baroreflex control of muscle sympathetic nerve activity (MSNA) during abrupt decreases in mean arterial pressure (MAP) and evaluated whether endurance training alters baroreflex function. Acute hypotension was induced nonpharmacologically in 14 healthy subjects, of which 7 were of high fitness (HF) and 7 were of average fitness (AF), by releasing a unilateral arterial thigh cuff after 9 min of resting ischemia under two conditions: control, which used aortic and carotid baroreflex (ABR and CBR, respectively) deactivation; and suction, which used ABR deactivation alone. The application of neck suction to counteract changes in carotid sinus transmural pressure during cuff release significantly attenuated the MSNA response (which increased 134 +/- 32 U/14 s) compared with control (which increased 195 +/- 43 U/14 s) and caused a greater decrease in MAP (19 +/- 2 vs. 15 +/- 2 mmHg; P < 0.05). Furthermore, during both trials, the HF subjects exhibited a greater decrease in MAP compared with AF subjects despite an augmented baroreflex control of MSNA. These data indicate that the CBR contributes importantly to the MSNA response during acute systemic hypotension. Additionally, we suggest that an impaired control of vascular reactivity hinders blood pressure regulation in HF subjects.

  20. Arterial baroreflex control of sympathetic nerve activity during acute hypotension: effect of fitness.

    PubMed

    Fadel, P J; Stromstad, M; Hansen, J; Sander, M; Horn, K; Ogoh, S; Smith, M L; Secher, N H; Raven, P B

    2001-06-01

    We examined arterial baroreflex control of muscle sympathetic nerve activity (MSNA) during abrupt decreases in mean arterial pressure (MAP) and evaluated whether endurance training alters baroreflex function. Acute hypotension was induced nonpharmacologically in 14 healthy subjects, of which 7 were of high fitness (HF) and 7 were of average fitness (AF), by releasing a unilateral arterial thigh cuff after 9 min of resting ischemia under two conditions: control, which used aortic and carotid baroreflex (ABR and CBR, respectively) deactivation; and suction, which used ABR deactivation alone. The application of neck suction to counteract changes in carotid sinus transmural pressure during cuff release significantly attenuated the MSNA response (which increased 134 +/- 32 U/14 s) compared with control (which increased 195 +/- 43 U/14 s) and caused a greater decrease in MAP (19 +/- 2 vs. 15 +/- 2 mmHg; P < 0.05). Furthermore, during both trials, the HF subjects exhibited a greater decrease in MAP compared with AF subjects despite an augmented baroreflex control of MSNA. These data indicate that the CBR contributes importantly to the MSNA response during acute systemic hypotension. Additionally, we suggest that an impaired control of vascular reactivity hinders blood pressure regulation in HF subjects.

  1. Evaluation of Hearing in Children with Autism by Using TEOAE and ABR

    ERIC Educational Resources Information Center

    Tas, Abdullah; Yagiz, Recep; Tas, Memduha; Esme, Meral; Uzun, Cem; Karasalihoglu, Ahmet Rifat

    2007-01-01

    Assessment of auditory abilities is important in the diagnosis and treatment of children with autism. The aim was to evaluate hearing objectively by using transient evoked otoacoustic emission (TEOAE) and auditory brainstem response (ABR). Tests were performed on 30 children with autism and 15 typically developing children, following otomicroscopy…

  2. Adaptive Significance of Quorum Sensing-Dependent Regulation of Rhamnolipids by Integration of Growth Rate in Burkholderia glumae: A Trade-Off between Survival and Efficiency.

    PubMed

    Nickzad, Arvin; Déziel, Eric

    2016-01-01

    Quorum sensing (QS) is a cell density-dependent mechanism which enables a population of bacteria to coordinate cooperative behaviors in response to the accumulation of self-produced autoinducer signals in their local environment. An emerging framework is that the adaptive significance of QS in the regulation of production of costly extracellular metabolites ("public goods") is to maintain the homeostasis of cooperation. We investigated this model using the phytopathogenic bacterium Burkholderia glumae, which we have previously demonstrated uses QS to regulate the production of rhamnolipids, extracellular surface-active glycolipids promoting the social behavior called "swarming motility." Using mass spectrometric quantification and chromosomal lux-based gene expression, we made the unexpected finding that when unrestricted nutrient resources are provided, production of rhamnolipids is carried out completely independently of QS regulation. This is a unique observation among known QS-controlled factors in bacteria. On the other hand, under nutrient-limited conditions, QS then becomes the main regulating mechanism, significantly enhancing the specific rhamnolipids yield. Accordingly, decreasing nutrient concentrations amplifies rhamnolipid biosynthesis gene expression, revealing a system where QS-dependent regulation is specifically triggered by the growth rate of the population, rather than by its cell density. Furthermore, a gradual increase in QS signal specific concentration upon decrease of specific growth rate suggests a reduction in quorum threshold, which reflects an increase in cellular demand for production of QS-dependent target gene product at low density populations. Integration of growth rate with QS as a decision-making mechanism for biosynthesis of costly metabolites, such as rhamnolipids, could serve to assess the demand and timing for expanding the carrying capacity of a population through spatial expansion mechanisms, such as swarming motility, thus promoting the chances of survival, even if the cell density might not be high enough for an otherwise efficient production of rhamnolipids. In conclusion, we propose that the adaptive significance of growth rate-dependent functionality of QS in biosynthesis of costly public goods lies within providing a regulatory mechanism for selecting the optimal trade-off between survival and efficiency.

  3. The Auditory Brain-Stem Response to Complex Sounds: A Potential Biomarker for Guiding Treatment of Psychosis

    PubMed Central

    Tarasenko, Melissa A.; Swerdlow, Neal R.; Makeig, Scott; Braff, David L.; Light, Gregory A.

    2014-01-01

    Cognitive deficits limit psychosocial functioning in schizophrenia. For many patients, cognitive remediation approaches have yielded encouraging results. Nevertheless, therapeutic response is variable, and outcome studies consistently identify individuals who respond minimally to these interventions. Biomarkers that can assist in identifying patients likely to benefit from particular forms of cognitive remediation are needed. Here, we describe an event-related potential (ERP) biomarker – the auditory brain-stem response (ABR) to complex sounds (cABR) – that appears to be particularly well-suited for predicting response to at least one form of cognitive remediation that targets auditory information processing. Uniquely, the cABR quantifies the fidelity of sound encoded at the level of the brainstem and midbrain. This ERP biomarker has revealed auditory processing abnormalities in various neurodevelopmental disorders, correlates with functioning across several cognitive domains, and appears to be responsive to targeted auditory training. We present preliminary cABR data from 18 schizophrenia patients and propose further investigation of this biomarker for predicting and tracking response to cognitive interventions. PMID:25352811

  4. Self-Medication with Antibiotics, Attitude and Knowledge of Antibiotic Resistance among Community Residents and Undergraduate Students in Northwest Nigeria.

    PubMed

    Ajibola, Olumide; Omisakin, Olusola Akintoye; Eze, Anthonius Anayochukwu; Omoleke, Semeeh Akinwale

    2018-04-27

    This study set out to evaluate self-medicated antibiotics and knowledge of antibiotic resistance among undergraduate students and community members in northern Nigeria. Antibiotic consumption pattern, source of prescription, illnesses commonly treated, attitude towards antibiotics, and knowledge of antibiotic resistance were explored using a structured questionnaire. Responses were analyzed and summarized using descriptive statistics. Of the 1230 respondents from undergraduate students and community members, prescription of antibiotics by a physician was 33% and 57%, respectively, amongst undergraduate students and community members. We tested the respondents’ knowledge of antibiotic resistance (ABR) and found that undergraduate students displayed less knowledge that self-medication could lead to ABR (32.6% and 42.2% respectively). Self-medication with antibiotics is highly prevalent in Northwest Nigeria, with most medicines being purchased from un-licensed stores without prescription from a physician. We also observed a significant gap in respondents’ knowledge of ABR. There is an urgent need for public health authorities in Nigeria to enforce existing laws on antibiotics sales and enlighten the people on the dangers of ABR.

  5. Hearing assessment during deep brain stimulation of the central nucleus of the inferior colliculus and dentate cerebellar nucleus in rat.

    PubMed

    Smit, Jasper V; Jahanshahi, Ali; Janssen, Marcus L F; Stokroos, Robert J; Temel, Yasin

    2017-01-01

    Recently it has been shown in animal studies that deep brain stimulation (DBS) of auditory structures was able to reduce tinnitus-like behavior. However, the question arises whether hearing might be impaired when interfering in auditory-related network loops with DBS. The auditory brainstem response (ABR) was measured in rats during high frequency stimulation (HFS) and low frequency stimulation (LFS) in the central nucleus of the inferior colliculus (CIC, n  = 5) or dentate cerebellar nucleus (DCBN, n  = 5). Besides hearing thresholds using ABR, relative measures of latency and amplitude can be extracted from the ABR. In this study ABR thresholds, interpeak latencies (I-III, III-V, I-V) and V/I amplitude ratio were measured during off-stimulation state and during LFS and HFS. In both the CIC and the CNBN groups, no significant differences were observed for all outcome measures. DBS in both the CIC and the CNBN did not have adverse effects on hearing measurements. These findings suggest that DBS does not hamper physiological processing in the auditory circuitry.

  6. Recent Changes to ABR Maintenance of Certification Part 4 (PQI): Acknowledgment of Radiologists' Activities to Improve Quality and Safety.

    PubMed

    Donnelly, Lane F; Mathews, Vincent P; Laszakovits, David J; Jackson, Valerie P; Guiberteau, Milton J

    2016-02-01

    The ABR has recently reviewed and revised its policy establishing how ABR diplomates may comply with requirements for Maintenance of Certification Part 4: Practice Quality Improvement (PQI). The changes were deemed necessary by the Board of Trustees to acknowledge and credit the numerous ways in which radiology professionals contribute to improving patient care through existing and evolving activities available to them within the radiology community. In addition to meeting requirements by completing a traditional PQI project, the policy revision now allows diplomates to meet criteria by completing one of a number of activities in an expanded spectrum of PQI options recognized by the ABR. The new policy also acknowledges the maturing state of quality improvement science by permitting PQI projects to use "any standard quality improvement methodology," such as Six Sigma, Lean, the Institute for Healthcare Improvement's Model for Improvement, and others in addition to the previously prescribed three-phase plan-do-study-act format. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  7. Cross-talk between abscisic acid-dependent and abscisic acid-independent pathways during abiotic stress.

    PubMed

    Roychoudhury, Aryadeep; Paul, Saikat; Basu, Supratim

    2013-07-01

    Salinity, drought and low temperature are the common forms of abiotic stress encountered by land plants. To cope with these adverse environmental factors, plants execute several physiological and metabolic responses. Both osmotic stress (elicited by water deficit or high salt) and cold stress increase the endogenous level of the phytohormone abscisic acid (ABA). ABA-dependent stomatal closure to reduce water loss is associated with small signaling molecules like nitric oxide, reactive oxygen species and cytosolic free calcium, and mediated by rapidly altering ion fluxes in guard cells. ABA also triggers the expression of osmotic stress-responsive (OR) genes, which usually contain single/multiple copies of cis-acting sequence called abscisic acid-responsive element (ABRE) in their upstream regions, mostly recognized by the basic leucine zipper-transcription factors (TFs), namely, ABA-responsive element-binding protein/ABA-binding factor. Another conserved sequence called the dehydration-responsive element (DRE)/C-repeat, responding to cold or osmotic stress, but not to ABA, occurs in some OR promoters, to which the DRE-binding protein/C-repeat-binding factor binds. In contrast, there are genes or TFs containing both DRE/CRT and ABRE, which can integrate input stimuli from salinity, drought, cold and ABA signaling pathways, thereby enabling cross-tolerance to multiple stresses. A strong candidate that mediates such cross-talk is calcium, which serves as a common second messenger for abiotic stress conditions and ABA. The present review highlights the involvement of both ABA-dependent and ABA-independent signaling components and their interaction or convergence in activating the stress genes. We restrict our discussion to salinity, drought and cold stress.

  8. Effect of middle ear fluid on sound transmission and auditory brainstem response in guinea pigs.

    PubMed

    Guan, Xiying; Gan, Rong Z

    2011-07-01

    Combined measurements of middle ear transfer function and auditory brainstem response (ABR) in live guinea pigs with middle ear effusion (MEE) are reported in this paper. The MEE model was created by injecting saline into the middle ear cavity. Vibrations of the tympanic membrane (TM), the tip of the incus, and the round window membrane (RWM) were measured with a laser vibrometer at frequencies of 0.2-40 kHz when the middle ear fluid increased from 0 to 0.2 ml (i.e., full fill of the cavity). The click and pure tone ABRs were recorded as the middle ear fluid increased. Fluid introduction reduced mobility of the TM, incus and RWM mainly at high frequencies (f > 1 kHz). The magnitude of this reduction was related to the volume of fluid. The displacement transmission ratio of the TM to incus varied with frequency and fluid level. The volume displacement ratio of the oval window to round window was approximately 1.0 over most frequencies. Elevation of ABR thresholds and prolongation of ABR latencies were observed as fluid level increased. Reduction of TM displacement correlated well with elevation of ABR threshold at 0.5-8 kHz. Alterations in the ratio of ossicular displacements before and after fluid induction are consistent with fluid-induced changes in complex ossicular motions. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Air and Bone Conduction Frequency-specific Auditory Brainstem Response in Children with Agenesis of the External Auditory Canal

    PubMed Central

    Sleifer, Pricila; Didoné, Dayane Domeneghini; Keppeler, Ísis Bicca; Bueno, Claudine Devicari; Riesgo, Rudimar dos Santos

    2017-01-01

    Introduction  The tone-evoked auditory brainstem responses (tone-ABR) enable the differential diagnosis in the evaluation of children until 12 months of age, including those with external and/or middle ear malformations. The use of auditory stimuli with frequency specificity by air and bone conduction allows characterization of hearing profile. Objective  The objective of our study was to compare the results obtained in tone-ABR by air and bone conduction in children until 12 months, with agenesis of the external auditory canal. Method  The study was cross-sectional, observational, individual, and contemporary. We conducted the research with tone-ABR by air and bone conduction in the frequencies of 500 Hz and 2000 Hz in 32 children, 23 boys, from one to 12 months old, with agenesis of the external auditory canal. Results  The tone-ABR thresholds were significantly elevated for air conduction in the frequencies of 500 Hz and 2000 Hz, while the thresholds of bone conduction had normal values in both ears. We found no statistically significant difference between genders and ears for most of the comparisons. Conclusion  The thresholds obtained by bone conduction did not alter the thresholds in children with conductive hearing loss. However, the conductive hearing loss alter all thresholds by air conduction. The tone-ABR by bone conduction is an important tool for assessing cochlear integrity in children with agenesis of the external auditory canal under 12 months. PMID:29018492

  10. In silico analysis of cis-acting regulatory elements in 5' regulatory regions of sucrose transporter gene families in rice (Oryza sativa Japonica) and Arabidopsis thaliana.

    PubMed

    Ibraheem, Omodele; Botha, Christiaan E J; Bradley, Graeme

    2010-12-01

    The regulation of gene expression involves a multifarious regulatory system. Each gene contains a unique combination of cis-acting regulatory sequence elements in the 5' regulatory region that determines its temporal and spatial expression. Cis-acting regulatory elements are essential transcriptional gene regulatory units; they control many biological processes and stress responses. Thus a full understanding of the transcriptional gene regulation system will depend on successful functional analyses of cis-acting elements. Cis-acting regulatory elements present within the 5' regulatory region of the sucrose transporter gene families in rice (Oryza sativa Japonica cultivar-group) and Arabidopsis thaliana, were identified using a bioinformatics approach. The possible cis-acting regulatory elements were predicted by scanning 1.5kbp of 5' regulatory regions of the sucrose transporter genes translational start sites, using Plant CARE, PLACE and Genomatix Matinspector professional databases. Several cis-acting regulatory elements that are associated with plant development, plant hormonal regulation and stress response were identified, and were present in varying frequencies within the 1.5kbp of 5' regulatory region, among which are; A-box, RY, CAT, Pyrimidine-box, Sucrose-box, ABRE, ARF, ERE, GARE, Me-JA, ARE, DRE, GA-motif, GATA, GT-1, MYC, MYB, W-box, and I-box. This result reveals the probable cis-acting regulatory elements that possibly are involved in the expression and regulation of sucrose transporter gene families in rice and Arabidopsis thaliana during cellular development or environmental stress conditions. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Spatial and temporal variation in the community prevalence of antibiotic resistance in Bangladesh: an integrated surveillance study protocol.

    PubMed

    Rousham, Emily; Unicomb, Leanne; Wood, Paul; Smith, Michael; Asaduzzaman, Muhammad; Islam, Mohammad Aminul

    2018-04-28

    Increasing antibiotic resistance (ABR) in low-income and middle-income countries such as Bangladesh presents a major health threat. However, assessing the scale of the health risk is problematic in the absence of reliable data on the community prevalence of antibiotic-resistant bacteria. We describe the protocol for a small-scale integrated surveillance programme that aims to quantify the prevalence of colonisation with antibiotic-resistant bacteria and concentrations of antibiotic-resistant genes from a 'One Health' perspective. The holistic assessment of ABR in humans, animals and within the environment in urban and rural Bangladesh will generate comprehensive data to inform human health risk. The study design focuses on three exposure-relevant sites where there is enhanced potential for transmission of ABR between humans, animals and the environment: (1) rural poultry-owning households, (2) commercial poultry farms and (3) urban live-bird markets. The comparison of ABR prevalence in human groups with high and low exposure to farming and poultry will enable us to test the hypothesis that ABR bacteria and genes from the environment and food-producing animals are potential sources of transmission to humans. Escherichia coli is used as an ABR indicator organism due to its widespread environmental presence and colonisation in both the human and animal gastrointestinal tract. The study has been approved by the Institutional Review Board of the International Centre for Diarrhoeal Disease Research, Bangladesh, and Loughborough University Ethics Committee. Data for the project will be stored on the open access repository of the Centre for Ecology and Hydrology, Natural Environment Research Council. The results of this study will be published in peer-reviewed journals and presented at national and international conferences. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients.

    PubMed

    Sosenko, Jay M; Skyler, Jay S; Palmer, Jerry P; Krischer, Jeffrey P; Yu, Liping; Mahon, Jeffrey; Beam, Craig A; Boulware, David C; Rafkin, Lisa; Schatz, Desmond; Eisenbarth, George

    2013-09-01

    We assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D). TrialNet Natural History Study participants (n = 784) were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those positive for at least one autoantibody were subsequently tested for ICA and ZnT8A. An autoantibody risk score (ABRS) was developed from a proportional hazards model that combined autoantibody levels from each autoantibody along with their designations of positivity and negativity. The ABRS was strongly predictive of T1D (hazard ratio [with 95% CI] 2.72 [2.23-3.31], P < 0.001). Receiver operating characteristic curve areas (with 95% CI) for the ABRS revealed good predictability (0.84 [0.78-0.90] at 2 years, 0.81 [0.74-0.89] at 3 years, P < 0.001 for both). The composite of levels from the five autoantibodies was predictive of T1D before and after an adjustment for the positivity or negativity of autoantibodies (P < 0.001). The findings were almost identical when ICA was excluded from the risk score model. The combination of the ABRS and the previously validated Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) predicted T1D more accurately (0.93 [0.88-0.98] at 2 years, 0.91 [0.83-0.99] at 3 years) than either the DPTRS or the ABRS alone (P ≤ 0.01 for all comparisons). These findings show the importance of considering autoantibody levels in assessing the risk of T1D. Moreover, levels of multiple autoantibodies can be incorporated into an ABRS that accurately predicts T1D.

  13. The Prediction of Type 1 Diabetes by Multiple Autoantibody Levels and Their Incorporation Into an Autoantibody Risk Score in Relatives of Type 1 Diabetic Patients

    PubMed Central

    Sosenko, Jay M.; Skyler, Jay S.; Palmer, Jerry P.; Krischer, Jeffrey P.; Yu, Liping; Mahon, Jeffrey; Beam, Craig A.; Boulware, David C.; Rafkin, Lisa; Schatz, Desmond; Eisenbarth, George

    2013-01-01

    OBJECTIVE We assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS TrialNet Natural History Study participants (n = 784) were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those positive for at least one autoantibody were subsequently tested for ICA and ZnT8A. An autoantibody risk score (ABRS) was developed from a proportional hazards model that combined autoantibody levels from each autoantibody along with their designations of positivity and negativity. RESULTS The ABRS was strongly predictive of T1D (hazard ratio [with 95% CI] 2.72 [2.23–3.31], P < 0.001). Receiver operating characteristic curve areas (with 95% CI) for the ABRS revealed good predictability (0.84 [0.78–0.90] at 2 years, 0.81 [0.74–0.89] at 3 years, P < 0.001 for both). The composite of levels from the five autoantibodies was predictive of T1D before and after an adjustment for the positivity or negativity of autoantibodies (P < 0.001). The findings were almost identical when ICA was excluded from the risk score model. The combination of the ABRS and the previously validated Diabetes Prevention Trial–Type 1 Risk Score (DPTRS) predicted T1D more accurately (0.93 [0.88–0.98] at 2 years, 0.91 [0.83–0.99] at 3 years) than either the DPTRS or the ABRS alone (P ≤ 0.01 for all comparisons). CONCLUSIONS These findings show the importance of considering autoantibody levels in assessing the risk of T1D. Moreover, levels of multiple autoantibodies can be incorporated into an ABRS that accurately predicts T1D. PMID:23818528

  14. Cooperation between STAT5 and phosphatidylinositol 3-kinase in the IL-3-dependent survival of a bone marrow derived cell line.

    PubMed

    Rosa Santos, S C; Dumon, S; Mayeux, P; Gisselbrecht, S; Gouilleux, F

    2000-02-24

    Cytokine-dependent activation of distinct signaling pathways is a common scheme thought to be required for the subsequent programmation into cell proliferation and survival. The PI 3-kinase/Akt, Ras/MAP kinase, Ras/NFIL3 and JAK/STAT pathways have been shown to participate in cytokine mediated suppression of apoptosis in various cell types. However the relative importance of these signaling pathways seems to depend on the cellular context. In several cases, individual inhibition of each pathway is not sufficient to completely abrogate cytokine mediated cell survival suggesting that cooperation between these pathways is required. Here we showed that individual inhibition of STAT5, PI 3-kinase or MEK activities did not or weakly affected the IL-3 dependent survival of the bone marrow derived Ba/F3 cell line. However, the simultaneous inhibition of STAT5 and PI 3-kinase activities but not that of STAT5 and MEK reduced the IL-3 dependent survival of Ba/F3. Analysis of the expression of the Bcl-2 members indicated that phosphorylation of Bad and Bcl-x expression which are respectively regulated by the PI 3-kinase/Akt pathway and STAT5 probably explain this cooperation. Furthermore, we showed by co-immunoprecipitation studies and pull down experiments with fusion proteins encoding the GST-SH2 domains of p85 that STAT5 in its phosphorylated form interacts with the p85 subunit of the PI 3-kinase. These results indicate that the activations of STAT5 and the PI 3-kinase by IL-3 in Ba/F3 cells are tightly connected and cooperate to mediate IL-3-dependent suppression of apoptosis by modulating Bad phosphorylation and Bcl-x expression.

  15. Effects of noise exposure on young adults with normal audiograms I: Electrophysiology.

    PubMed

    Prendergast, Garreth; Guest, Hannah; Munro, Kevin J; Kluk, Karolina; Léger, Agnès; Hall, Deborah A; Heinz, Michael G; Plack, Christopher J

    2017-02-01

    Noise-induced cochlear synaptopathy has been demonstrated in numerous rodent studies. In these animal models, the disorder is characterized by a reduction in amplitude of wave I of the auditory brainstem response (ABR) to high-level stimuli, whereas the response at threshold is unaffected. The aim of the present study was to determine if this disorder is prevalent in young adult humans with normal audiometric hearing. One hundred and twenty six participants (75 females) aged 18-36 were tested. Participants had a wide range of lifetime noise exposures as estimated by a structured interview. Audiometric thresholds did not differ across noise exposures up to 8 kHz, although 16-kHz audiometric thresholds were elevated with increasing noise exposure for females but not for males. ABRs were measured in response to high-pass (1.5 kHz) filtered clicks of 80 and 100 dB peSPL. Frequency-following responses (FFRs) were measured to 80 dB SPL pure tones from 240 to 285 Hz, and to 80 dB SPL 4 kHz pure tones amplitude modulated at frequencies from 240 to 285 Hz (transposed tones). The bandwidth of the ABR stimuli and the carrier frequency of the transposed tones were chosen to target the 3-6 kHz characteristic frequency region which is usually associated with noise damage in humans. The results indicate no relation between noise exposure and the amplitude of the ABR. In particular, wave I of the ABR did not decrease with increasing noise exposure as predicted. ABR wave V latency increased with increasing noise exposure for the 80 dB peSPL click. High carrier-frequency (envelope) FFR signal-to-noise ratios decreased as a function of noise exposure in males but not females. However, these correlations were not significant after the effects of age were controlled. The results suggest either that noise-induced cochlear synaptopathy is not a significant problem in young, audiometrically normal adults, or that the ABR and FFR are relatively insensitive to this disorder in young humans, although it is possible that the effects become more pronounced with age. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Auditory Brainstem Response Altered in Humans With Noise Exposure Despite Normal Outer Hair Cell Function

    PubMed Central

    Bramhall, Naomi F.; Konrad-Martin, Dawn; McMillan, Garnett P.; Griest, Susan E.

    2017-01-01

    Objectives Recent animal studies demonstrated that cochlear synaptopathy, a partial loss of inner hair cell-auditory nerve fiber synapses, can occur in response to noise exposure without any permanent auditory threshold shift. In animal models, this synaptopathy is associated with a reduction in the amplitude of wave I of the auditory brainstem response (ABR). The goal of this study was to determine whether higher lifetime noise exposure histories in young people with clinically normal pure-tone thresholds are associated with lower ABR wave I amplitudes. Design Twenty-nine young military Veterans and 35 non Veterans (19 to 35 years of age) with normal pure-tone thresholds were assigned to 1 of 4 groups based on their self-reported lifetime noise exposure history and Veteran status. Suprathreshold ABR measurements in response to alternating polarity tone bursts were obtained at 1, 3, 4, and 6 kHz with gold foil tiptrode electrodes placed in the ear canal. Wave I amplitude was calculated from the difference in voltage at the positive peak and the voltage at the following negative trough. Distortion product otoacoustic emission input/output functions were collected in each participant at the same four frequencies to assess outer hair cell function. Results After controlling for individual differences in sex and distortion product otoacoustic emission amplitude, the groups containing participants with higher reported histories of noise exposure had smaller ABR wave I amplitudes at suprathreshold levels across all four frequencies compared with the groups with less history of noise exposure. Conclusions Suprathreshold ABR wave I amplitudes were reduced in Veterans reporting high levels of military noise exposure and in non Veterans reporting any history of firearm use as compared with Veterans and non Veterans with lower levels of reported noise exposure history. The reduction in ABR wave I amplitude in the groups with higher levels of noise exposure cannot be accounted for by sex or variability in outer hair cell function. This change is similar to the decreased ABR wave I amplitudes observed in animal models of noise-induced cochlear synaptopathy. However, without post mortem examination of the temporal bone, no direct conclusions can be drawn concerning the presence of synaptopathy in the study groups with higher noise exposure histories. PMID:27992391

  17. Blocking caspase-3-dependent pathway preserves hair cells from salicylate-induced apoptosis in the guinea pig cochlea.

    PubMed

    Feng, Hao; Yin, Shi-Hua; Tang, An-Zhou

    2011-07-01

    In the present study, we aim to explore whether the caspase-3-dependent pathway is involved in the apoptotic cell death that occurs in the hair cells (HCs) of guinea pig cochlea following a salicylate treatment. Guinea pigs received sodium salicylate (Na-SA), at a dose of 200 mg·kg(-1)·d(-1) i.p., as a vehicle for 5 consecutive days. In some experiments, N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone (zDEVD-FMK), a specific apoptosis inhibitor, was directly applied into the cochlea via the round window niche (RWN) prior to salicylate treatment for determination of caspase-3 activation. Alterations in auditory function were evaluated with auditory brainstem responses (ABR) thresholds. Caspase-3 activity was determined by measuring the proteolytic cleavage product of caspase-3 (N-terminated peptide substrate). DNA fragmentation within the nuclei was examined with a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. Ultrastructure variation in the target cell was assessed by electron microscopy (EM). Salicylate treatment initiated an obvious elevation in ABR thresholds with a maximum average shift of 60 dB sound pressure level (SPL), and caused significant apoptosis in both inner (IHCs) and outer (OHCs) hair cells resulted from an evident increasing in immunoreactivity to caspase-3 protease. Transmission electron microscopy (TEM) displayed chromatin condensation and nucleus margination accompanied by cell body shrinkage in the OHCs, but not in the IHCs. Scanning electron microscopy (SEM) showed breakdown, fusion, and loss in the stereociliary bundles at the apex of OHCs rather than IHCs. zDEVD-FMK pretreatment prior to salicylate injection substantially attenuated an expression of the apoptotic protease and protected HCs against apoptotic death, followed by a moderate relief in the thresholds of ABR, an alleviation in the submicroscopic structure was also identified. In particular, disorientation and insertion in the hair bundles at the apex of OHCs was exhibited though no classic apoptotic change found. The above changes were either prevented or significantly attenuated by zDEVD-FMK. These findings indicate that salicylate could damage cochlear hair cells via inducing apoptosis associated with caspase-3 activation.

  18. Selection methods regulate evolution of cooperation in digital evolution

    PubMed Central

    Lichocki, Paweł; Floreano, Dario; Keller, Laurent

    2014-01-01

    A key, yet often neglected, component of digital evolution and evolutionary models is the ‘selection method’ which assigns fitness (number of offspring) to individuals based on their performance scores (efficiency in performing tasks). Here, we study with formal analysis and numerical experiments the evolution of cooperation under the five most common selection methods (proportionate, rank, truncation-proportionate, truncation-uniform and tournament). We consider related individuals engaging in a Prisoner's Dilemma game where individuals can either cooperate or defect. A cooperator pays a cost, whereas its partner receives a benefit, which affect their performance scores. These performance scores are translated into fitness by one of the five selection methods. We show that cooperation is positively associated with the relatedness between individuals under all selection methods. By contrast, the change in the performance benefit of cooperation affects the populations’ average level of cooperation only under the proportionate methods. We also demonstrate that the truncation and tournament methods may introduce negative frequency-dependence and lead to the evolution of polymorphic populations. Using the example of the evolution of cooperation, we show that the choice of selection method, though it is often marginalized, can considerably affect the evolutionary dynamics. PMID:24152811

  19. Individual variation behind the evolution of cooperation.

    PubMed

    Barta, Zoltán

    2016-02-05

    Life on Earth has two remarkable properties. The first is variation: even apart from the vast number of extant species, there are considerable differences between individuals within a single species. The second property is cooperation. It is surprising that until recently the interactions between these two properties have rarely been addressed from an evolutionary point of view. Here, I concentrate on how inter-individual differences influence the evolution of cooperation. First, I deal with cases where individuality is maintained by random processes like mutation or phenotypic noise. Second, I examine when differences in state cause differences in behaviour. Finally, I investigate the effects of individual role specialization. Variation can be important in several ways. Increased random variation can change the expectation about cooperativeness of future partners, altering behaviour in a current relationship. Differences in state may serve as a book-keeping mechanism that is necessary for the evolution of reciprocity. If the cost of cooperation can depend on state then strategic regulation of state makes it possible to coerce partners to cooperate. If conditions force individuals to specialize, cooperation becomes more valuable. My review of theoretical models suggests that variation plays an important role in the evolution of cooperation. © 2016 The Author(s).

  20. The Arabidopsis Phytocystatin AtCYS5 Enhances Seed Germination and Seedling Growth under Heat Stress Conditions.

    PubMed

    Song, Chieun; Kim, Taeyoon; Chung, Woo Sik; Lim, Chae Oh

    2017-08-01

    Phytocystatins (PhyCYSs) are plant-specific proteinaceous inhibitors that are implicated in protein turnover and stress responses. Here, we characterized a PhyCYS from Arabidopsis thaliana , which was designated AtCYS5. RT-qPCR analysis showed that the expression of AtCYS5 in germinating seeds was induced by heat stress (HS) and exogenous abscisic acid (ABA) treatment. Analysis of the expression of the β -glucuronidase reporter gene under the control of the AtCYS5 promoter showed that AtCYS5 expression during seed germination was induced by HS and ABA. Constitutive overexpression of AtCYS5 driven by the cauliflower mosaic virus 35S promoter led to enhanced HS tolerance in transgenic Arabidopsis , which was characterized by higher fresh weight and root length compared to wild-type (WT) and knockout ( cys5 ) plants grown under HS conditions. The HS tolerance of At-CYS5 -overexpressing transgenic plants was associated with increased insensitivity to exogenous ABA during both seed germination and post-germination compared to WT and cys5 . Although no HS elements were identified in the 5'-flanking region of AtCYS5 , canonical ABA-responsive elements (ABREs) were detected. AtCYS5 was upregulated in ABA-treated protoplasts transiently co-expressing this gene and genes encoding bZIP ABRE-binding factors (ABFs and AREB3). In the absence of ABA, ABF1 and ABF3 directly bound to the ABREs in the AtCYS5 promoter, which activated the transcription of this gene in the presence of ABA. These results suggest that an ABA-dependent pathway plays a positive role in the HS-responsive expression of AtCYS5 during seed germination and post-germination growth.

  1. The Impact of Clinical History on the Threshold Estimation of Auditory Brainstem Response Results for Infants

    ERIC Educational Resources Information Center

    Zaitoun, Maha; Cumming, Steven; Purcell, Alison; O'Brien, Katie

    2017-01-01

    Purpose: This study assesses the impact of patient clinical history on audiologists' performance when interpreting auditory brainstem response (ABR) results. Method: Fourteen audiologists' accuracy in estimating hearing threshold for 16 infants through interpretation of ABR traces was compared on 2 occasions at least 5 months apart. On the 1st…

  2. Effect of High-Pass Filtering on the Neonatal Auditory Brainstem Response to Air- and Bone-Conducted Clicks.

    ERIC Educational Resources Information Center

    Stuart, Andrew; Yang, Edward Y.

    1994-01-01

    Simultaneous 3- channel recorded auditory brainstem responses (ABR) were obtained from 20 neonates with various high-pass filter settings and low intensity levels. Results support the advocacy of less restrictive high-pass filtering for neonatal and infant ABR screening to air-conducted and bone-conducted clicks. (Author/JDD)

  3. Auditory Brainstem Evoked Responses in Newborns with Down Syndrome

    ERIC Educational Resources Information Center

    Kittler, Phyllis M.; Phan, Ha T. T.; Gardner, Judith M.; Miroshnichenko, Inna; Gordon, Anne; Karmel, Bernard Z.

    2009-01-01

    Auditory brainstem evoked responses (ABRs) were compared in 15 newborns with Down syndrome and 15 sex-, age-, and weight-matched control newborns. Participants had normal ABRs based upon values specific to 32- to 42-weeks postconceptional age. Although Wave III and Wave V component latencies and the Wave I-III interpeak latency (IPL) were shorter…

  4. Auditory Brainstem Responses from Children Three Months to Three Years of Age: Normal Patterns of Response II.

    ERIC Educational Resources Information Center

    Gorga, Michael P.; And Others

    1989-01-01

    Auditory brainstem responses (ABR) were measured in 535 children from 3 months to 3 years of age. Results suggested that changes in wave V latency with age are due to central (neural) factors and that age-appropriate norms should be used in evaluations of ABR latencies in children. (Author/DB)

  5. 76 FR 21092 - Notice of Projects Approved or Rescinded for Consumptive Uses of Water

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-14

    .... 46. Anadarko E&P Company LP, Pad ID: Harry W Stryker Pad A, ABR- 201011044, Cogan House Township... Energy, LLC, Pad ID: Triana-Young Pad B, ABR-201012008, Hector Township, Potter County, Pa.; Consumptive...- 20100346, Harrison Township, Potter County, Pa.; Consumptive Use of up 4.000 mgd; Rescinded Date: December...

  6. 77 FR 23120 - Special Local Regulations; Lowcountry Splash Open Water Swim, Wando River and Cooper River, Mount...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-18

    ...-AA08 Special Local Regulations; Lowcountry Splash Open Water Swim, Wando River and Cooper River, Mount... at Patriots Point on the Cooper River. Approximately 600 swimmers will be participating in the swim... Special Local Regulations; Lowcountry Splash Open Water Swim, Wando River and Cooper River, Mount Pleasant...

  7. Androgenic Regulation of White Adipose Tissue-Prostate Cancer Interactions

    DTIC Science & Technology

    2012-05-01

    ijo.2011.953. Epub 2011 Feb 23. 6. Sharma PK, Singh R, Novakovic KR, Eaton JW, Grizzle WE, Singh S. CCR9 mediates PI3K/AKT-dependent antiapoptotic...Cooper, C.R., Novakovic , K.R., Grizzle, W.E., Lillard Jr., J.W., 2009. Serum CXCL13 positively correlates with prostatic disease, prostate-specific

  8. PAX5 tyrosine phosphorylation by SYK co-operatively functions with its serine phosphorylation to cancel the PAX5-dependent repression of BLIMP1: A mechanism for antigen-triggered plasma cell differentiation.

    PubMed

    Inagaki, Yuichiro; Hayakawa, Fumihiko; Hirano, Daiki; Kojima, Yuki; Morishita, Takanobu; Yasuda, Takahiko; Naoe, Tomoki; Kiyoi, Hitoshi

    2016-06-24

    Plasma cell differentiation is initiated by antigen stimulation of the B cell receptor (BCR) and is regulated by BLIMP1. Prior to the stimulation of BCR, BLIMP1 is suppressed by PAX5, which is a key transcriptional repressor that maintains B cell identity. The upregulation of BLIMP1 and subsequent suppression of PAX5 by BLIMP1 are observed after the BCR stimulation. These events are considered to trigger plasma cell differentiation; however, the mechanisms responsible currently remain unclear. We herein demonstrated that the BCR signaling component, SYK, caused PAX5 tyrosine phosphorylation in vitro and in cells. Transcriptional repression on the BLIMP1 promoter by PAX5 was attenuated by this phosphorylation. The BCR stimulation induced the phosphorylation of SYK, tyrosine phosphorylation of PAX5, and up-regulation of BLIMP1 mRNA expression in B cells. The tyrosine phosphorylation of PAX5 co-operatively functioned with PAX5 serine phosphorylation by ERK1/2, which was our previous findings, to cancel the PAX5-dependent repression of BLIMP1. This co-operation may be a trigger for plasma cell differentiation. These results imply that PAX5 phosphorylation by a BCR signal is the initial event in plasma cell differentiation. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Vasopressin increases human risky cooperative behavior

    PubMed Central

    Brunnlieb, Claudia; Nave, Gideon; Camerer, Colin F.; Schosser, Stephan; Vogt, Bodo; Münte, Thomas F.; Heldmann, Marcus

    2016-01-01

    The history of humankind is an epic of cooperation, which is ubiquitous across societies and increasing in scale. Much human cooperation occurs where it is risky to cooperate for mutual benefit because successful cooperation depends on a sufficient level of cooperation by others. Here we show that arginine vasopressin (AVP), a neuropeptide that mediates complex mammalian social behaviors such as pair bonding, social recognition and aggression causally increases humans’ willingness to engage in risky, mutually beneficial cooperation. In two double-blind experiments, male participants received either AVP or placebo intranasally and made decisions with financial consequences in the “Stag hunt” cooperation game. AVP increases humans’ willingness to cooperate. That increase is not due to an increase in the general willingness to bear risks or to altruistically help others. Using functional brain imaging, we show that, when subjects make the risky Stag choice, AVP down-regulates the BOLD signal in the left dorsolateral prefrontal cortex (dlPFC), a risk-integration region, and increases the left dlPFC functional connectivity with the ventral pallidum, an AVP receptor-rich region previously associated with AVP-mediated social reward processing in mammals. These findings show a previously unidentified causal role for AVP in social approach behavior in humans, as established by animal research. PMID:26858433

  10. Hearing threshold assessment in young children with electrocochleography (EcochG) and auditory brainstem responses (ABR): experience at the University Hospital of Ferrara.

    PubMed

    Aimoni, C; Ciorba, A; Bovo, R; Trevisi, P; Busi, M; Martini, A

    2010-10-01

    Electrophysiological evaluation is a fundamental procedure for the diagnostic assessment of hearing loss during infancy; in these cases, information concerning threshold level and auditory perception is particularly useful to establish a correct hearing rehabilitation program (hearing aids and cochlear implants). Purpose of this study is to underline the role of auditory brainstem responses (ABR) and electrocochleography (EcochG) in the definition of hearing loss in a selected group of children, referred to the Audiology Department of the University Hospital of Ferrara, for a tertiary level audiological assessment. A retrospective study of the paediatric patient database at the Audiology Department of the University Hospital of Ferrara has been performed. In a period between January 2000 and December 2007, a total of 272 paediatric cases have been identified (544 ears). An EM 12 Mercury apparatus has been used for the electrophysiological threshold identification (ABR and EcochG). Recordings were carried out under general anaesthesia, in a protected enviroment. In 19 of the 272 paediatric cases selected--38 ears (7%), the results of threshold evaluation through ABR were uncertain. The Ecochg recording resulted crucial for the final diagnosis in terms of definition of the hearing threshold level, and it was then possible to ensure the better hearing rehabilitation strategy. ABR has to be considered the first choice in hearing assessment strategy, either for screening or for diagnosis in newborns as well as in non-collaborating children; ECochG still may be considered a reliable diagnostic tool. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Comparison of threshold estimation in infants with hearing loss or normal hearing using auditory steady-state response evoked by narrow band CE-chirps and auditory brainstem response evoked by tone pips.

    PubMed

    Michel, Franck; Jørgensen, Kristoffer Foldager

    2017-02-01

    The objective of this study is to compare air-conduction thresholds obtained with ASSR evoked by narrow band (NB) CE-chirps and ABR evoked by tone pips (tpABR) in infants with various degrees of hearing loss. Thresholds were measured at 500, 1000, 2000 and 4000 Hz. Data on each participant were collected at the same day. Sixty-seven infants aged 4 d to 22 months (median age = 96 days), resulting in 57, 52, 87 and 56 ears for 500, 1000, 2000 and 4000 Hz, respectively. Statistical analysis was performed for ears with hearing loss (HL) and showed a very strong correlation between tpABR and ASSR evoked by NB CE-chirps: 0.90 (n = 28), 0.90 (n = 28), 0.96 (n = 42) and 0.95 (n = 30) for 500, 1000, 2000 and 4000 Hz, respectively. At these frequencies, the mean difference between tpABR and ASSR was -3.6 dB (± 7.0), -5.2 dB (± 7.3), -3.9 dB (± 5.2) and -5.2 dB (± 4.7). Linear regression analysis indicated that the relationship was not influenced by the degree of hearing loss. We propose that dB nHL to dB eHL correction values for ASSR evoked by NB CE-chirps should be 5 dB lower than values used for tpABR.

  12. A Comparison of Two Objective Measures of Binaural Processing: The Interaural Phase Modulation Following Response and the Binaural Interaction Component.

    PubMed

    Haywood, Nicholas R; Undurraga, Jaime A; Marquardt, Torsten; McAlpine, David

    2015-12-30

    There has been continued interest in clinical objective measures of binaural processing. One commonly proposed measure is the binaural interaction component (BIC), which is obtained typically by recording auditory brainstem responses (ABRs)-the BIC reflects the difference between the binaural ABR and the sum of the monaural ABRs (i.e., binaural - (left + right)). We have recently developed an alternative, direct measure of sensitivity to interaural time differences, namely, a following response to modulations in interaural phase difference (the interaural phase modulation following response; IPM-FR). To obtain this measure, an ongoing diotically amplitude-modulated signal is presented, and the interaural phase difference of the carrier is switched periodically at minima in the modulation cycle. Such periodic modulations to interaural phase difference can evoke a steady state following response. BIC and IPM-FR measurements were compared from 10 normal-hearing subjects using a 16-channel electroencephalographic system. Both ABRs and IPM-FRs were observed most clearly from similar electrode locations-differential recordings taken from electrodes near the ear (e.g., mastoid) in reference to a vertex electrode (Cz). Although all subjects displayed clear ABRs, the BIC was not reliably observed. In contrast, the IPM-FR typically elicited a robust and significant response. In addition, the IPM-FR measure required a considerably shorter recording session. As the IPM-FR magnitude varied with interaural phase difference modulation depth, it could potentially serve as a correlate of perceptual salience. Overall, the IPM-FR appears a more suitable clinical measure than the BIC. © The Author(s) 2015.

  13. Select antibiotics in leachate from closed and active landfills exceed thresholds for antibiotic resistance development.

    PubMed

    Chung, S S; Zheng, J S; Burket, S R; Brooks, B W

    2018-06-01

    Though antibiotic resistance (ABR) represents a major global health threat, contributions of landfill leachate to the life cycle of antibiotics and ABR development are poorly understood in rapidly urbanizing regions of developing countries. We selected one of the largest active landfills in Asia and two landfills that have been closed for 20 years to examine antibiotic occurrences in leachates and associated hazards during wet and dry season sampling events. We focused on some of the most commonly used human antibiotics in Hong Kong, one of the most populous Asian cities and the fourth most densely populated cities in the world. Seven antibiotics (cephalexin [CLX], chloramphenicol [CAP], ciprofloxacin [CIP], erythromycin [ERY], roxithromycin [ROX], trimethoprim [TMP], sulfamethoxazole [SMX]) were quantitated using HPLC-MS/MS generally following previously reported methods. Whereas CLX, CAP, ROX and SMX in leachates did not exceed ABR predicted no effect concentrations (PNECs), exceedances were observed for CIP, ERY and TMP in some study locations and on some dates. In fact, an ABR PNEC for CIP was exceeded in leachates during both sampling periods from all study locations, including leachates that are directly discharged to coastal systems. These findings highlight the importance of developing an advanced understanding of pharmaceutical access, usage and disposal practices, effectiveness of intervention strategies (e.g., leachate treatment technologies, drug take-back schemes), and contributions of landfill leachates to the life cycle of antibiotics and ABR development, particularly in rapidly urbanizing coastal regions with less advanced waste management systems than Hong Kong. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Deletion of Fmr1 Alters Function and Synaptic Inputs in the Auditory Brainstem

    PubMed Central

    Rotschafer, Sarah E.; Marshak, Sonya; Cramer, Karina S.

    2015-01-01

    Fragile X Syndrome (FXS), a neurodevelopmental disorder, is the most prevalent single-gene cause of autism spectrum disorder. Autism has been associated with impaired auditory processing, abnormalities in the auditory brainstem response (ABR), and reduced cell number and size in the auditory brainstem nuclei. FXS is characterized by elevated cortical responses to sound stimuli, with some evidence for aberrant ABRs. Here, we assessed ABRs and auditory brainstem anatomy in Fmr1 -/- mice, an animal model of FXS. We found that Fmr1 -/- mice showed elevated response thresholds to both click and tone stimuli. Amplitudes of ABR responses were reduced in Fmr1 -/- mice for early peaks of the ABR. The growth of the peak I response with sound intensity was less steep in mutants that in wild type mice. In contrast, amplitudes and response growth in peaks IV and V did not differ between these groups. We did not observe differences in peak latencies or in interpeak latencies. Cell size was reduced in Fmr1 -/- mice in the ventral cochlear nucleus (VCN) and in the medial nucleus of the trapezoid body (MNTB). We quantified levels of inhibitory and excitatory synaptic inputs in these nuclei using markers for presynaptic proteins. We measured VGAT and VGLUT immunolabeling in VCN, MNTB, and the lateral superior olive (LSO). VGAT expression in MNTB was significantly greater in the Fmr1 -/- mouse than in wild type mice. Together, these observations demonstrate that FXS affects peripheral and central aspects of hearing and alters the balance of excitation and inhibition in the auditory brainstem. PMID:25679778

  15. The Arabidopsis PLAT domain protein1 is critically involved in abiotic stress tolerance.

    PubMed

    Hyun, Tae Kyung; van der Graaff, Eric; Albacete, Alfonso; Eom, Seung Hee; Großkinsky, Dominik K; Böhm, Hannah; Janschek, Ursula; Rim, Yeonggil; Ali, Walid Wahid; Kim, Soo Young; Roitsch, Thomas

    2014-01-01

    Despite the completion of the Arabidopsis genome sequence, for only a relatively low percentage of the encoded proteins experimental evidence concerning their function is available. Plant proteins that harbour a single PLAT (Polycystin, Lipoxygenase, Alpha-toxin and Triacylglycerol lipase) domain and belong to the PLAT-plant-stress protein family are ubiquitously present in monocot and dicots. However, the function of PLAT-plant-stress proteins is still poorly understood. Therefore, we have assessed the function of the uncharacterised Arabidopsis PLAT-plant-stress family members through a combination of functional genetic and physiological approaches. PLAT1 overexpression conferred increased abiotic stress tolerance, including cold, drought and salt stress, while loss-of-function resulted in opposite effects on abiotic stress tolerance. Strikingly, PLAT1 promoted growth under non-stressed conditions. Abiotic stress treatments induced PLAT1 expression and caused expansion of its expression domain. The ABF/ABRE transcription factors, which are positive mediators of abscisic acid signalling, activate PLAT1 promoter activity in transactivation assays and directly bind to the ABRE elements located in this promoter in electrophoretic mobility shift assays. This suggests that PLAT1 represents a novel downstream target of the abscisic acid signalling pathway. Thus, we showed that PLAT1 critically functions as positive regulator of abiotic stress tolerance, but also is involved in regulating plant growth, and thereby assigned a function to this previously uncharacterised PLAT domain protein. The functional data obtained for PLAT1 support that PLAT-plant-stress proteins in general could be promising targets for improving abiotic stress tolerance without yield penalty.

  16. The Arabidopsis PLAT Domain Protein1 Is Critically Involved in Abiotic Stress Tolerance

    PubMed Central

    Eom, Seung Hee; Großkinsky, Dominik K.; Böhm, Hannah; Janschek, Ursula; Rim, Yeonggil; Ali, Walid Wahid; Kim, Soo Young; Roitsch, Thomas

    2014-01-01

    Despite the completion of the Arabidopsis genome sequence, for only a relatively low percentage of the encoded proteins experimental evidence concerning their function is available. Plant proteins that harbour a single PLAT (Polycystin, Lipoxygenase, Alpha-toxin and Triacylglycerol lipase) domain and belong to the PLAT-plant-stress protein family are ubiquitously present in monocot and dicots. However, the function of PLAT-plant-stress proteins is still poorly understood. Therefore, we have assessed the function of the uncharacterised Arabidopsis PLAT-plant-stress family members through a combination of functional genetic and physiological approaches. PLAT1 overexpression conferred increased abiotic stress tolerance, including cold, drought and salt stress, while loss-of-function resulted in opposite effects on abiotic stress tolerance. Strikingly, PLAT1 promoted growth under non-stressed conditions. Abiotic stress treatments induced PLAT1 expression and caused expansion of its expression domain. The ABF/ABRE transcription factors, which are positive mediators of abscisic acid signalling, activate PLAT1 promoter activity in transactivation assays and directly bind to the ABRE elements located in this promoter in electrophoretic mobility shift assays. This suggests that PLAT1 represents a novel downstream target of the abscisic acid signalling pathway. Thus, we showed that PLAT1 critically functions as positive regulator of abiotic stress tolerance, but also is involved in regulating plant growth, and thereby assigned a function to this previously uncharacterised PLAT domain protein. The functional data obtained for PLAT1 support that PLAT-plant-stress proteins in general could be promising targets for improving abiotic stress tolerance without yield penalty. PMID:25396746

  17. Auditory Brainstem Response Thresholds to Air- and Bone-Conducted CE-Chirps in Neonates and Adults

    ERIC Educational Resources Information Center

    Cobb, Kensi M.; Stuart, Andrew

    2016-01-01

    Purpose The purpose of this study was to compare auditory brainstem response (ABR) thresholds to air- and bone-conducted CE-Chirps in neonates and adults. Method Thirty-two neonates with no physical or neurologic challenges and 20 adults with normal hearing participated. ABRs were acquired with a starting intensity of 30 dB normal hearing level…

  18. 75 FR 51155 - Notice of Projects Approved for Consumptive Uses of Water

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-18

    ...: June 11, 2010. 35. Anadarko E&P Company, LP; Pad ID: David C Duncan Pad A, ABR- 20100635, Cascade.... Anadarko E&P Company, LP; Pad ID: COP Tract 289 C, ABR- 20100636, McHenry Township, Lycoming County, Pa.... Cairo, General Counsel, telephone: (717) 238-0423, ext. 306; fax: (717) 238-2436; e-mail: [email protected

  19. Self-adaptive trust based ABR protocol for MANETs using Q-learning.

    PubMed

    Kumar, Anitha Vijaya; Jeyapal, Akilandeswari

    2014-01-01

    Mobile ad hoc networks (MANETs) are a collection of mobile nodes with a dynamic topology. MANETs work under scalable conditions for many applications and pose different security challenges. Due to the nomadic nature of nodes, detecting misbehaviour is a complex problem. Nodes also share routing information among the neighbours in order to find the route to the destination. This requires nodes to trust each other. Thus we can state that trust is a key concept in secure routing mechanisms. A number of cryptographic protection techniques based on trust have been proposed. Q-learning is a recently used technique, to achieve adaptive trust in MANETs. In comparison to other machine learning computational intelligence techniques, Q-learning achieves optimal results. Our work focuses on computing a score using Q-learning to weigh the trust of a particular node over associativity based routing (ABR) protocol. Thus secure and stable route is calculated as a weighted average of the trust value of the nodes in the route and associativity ticks ensure the stability of the route. Simulation results show that Q-learning based trust ABR protocol improves packet delivery ratio by 27% and reduces the route selection time by 40% over ABR protocol without trust calculation.

  20. Self-Adaptive Trust Based ABR Protocol for MANETs Using Q-Learning

    PubMed Central

    Jeyapal, Akilandeswari

    2014-01-01

    Mobile ad hoc networks (MANETs) are a collection of mobile nodes with a dynamic topology. MANETs work under scalable conditions for many applications and pose different security challenges. Due to the nomadic nature of nodes, detecting misbehaviour is a complex problem. Nodes also share routing information among the neighbours in order to find the route to the destination. This requires nodes to trust each other. Thus we can state that trust is a key concept in secure routing mechanisms. A number of cryptographic protection techniques based on trust have been proposed. Q-learning is a recently used technique, to achieve adaptive trust in MANETs. In comparison to other machine learning computational intelligence techniques, Q-learning achieves optimal results. Our work focuses on computing a score using Q-learning to weigh the trust of a particular node over associativity based routing (ABR) protocol. Thus secure and stable route is calculated as a weighted average of the trust value of the nodes in the route and associativity ticks ensure the stability of the route. Simulation results show that Q-learning based trust ABR protocol improves packet delivery ratio by 27% and reduces the route selection time by 40% over ABR protocol without trust calculation. PMID:25254243

  1. Evoked potential application to study of echolocation in cetaceans

    NASA Astrophysics Data System (ADS)

    Supin, Alexander Ya.; Nactigall, Paul E.; Pawloski, Jeffrey; Au, Whitlow W. L.

    2002-05-01

    The evoked-potential (EP) method is effective in studies of hearing capabilities of cetaceans. However, until now EP studies in cetaceans were performed only in conditions of passive hearing by recording EP to external stimuli. Can this method be applied to study active echolocation in odontocetes? To answer this question, auditory brainstem evoked responses (ABR) were recorded in a false killer whale while the animal echolocated a target within an experiment in which the animal reported the target present or absent. The ABR collection was triggered by echolocation clicks. In these conditions, the recorded ABR pattern contained a duplicate set of waves. A comparison of ABR wave delays recorded during echolocation with those recorded during regular external stimulation has shown that the first set of waves is a response to the emitted click whereas the second one is a response to the echo. Both responses, to the emitted click and to the echo, were of comparable amplitude in spite of the intensity difference of these two sounds of more than 40 dB near the animal's head. This finding indicates some mechanisms releasing responses to echoes from masking by loud emitted clicks. The evoked-potential method may be productive to investigate these mechanisms.

  2. Whole Genome-Sequencing and Phylogenetic Analysis of a Historical Collection of Bacillus anthracis Strains from Danish Cattle

    PubMed Central

    Derzelle, Sylviane; Girault, Guillaume; Kokotovic, Branko; Angen, Øystein

    2015-01-01

    Bacillus anthracis, the causative agent of anthrax, is known as one of the most genetically monomorphic species. Canonical single-nucleotide polymorphism (SNP) typing and whole-genome sequencing were used to investigate the molecular diversity of eleven B. anthracis strains isolated from cattle in Denmark between 1935 and 1988. Danish strains were assigned into five canSNP groups or lineages, i.e. A.Br.001/002 (n = 4), A.Br.Ames (n = 2), A.Br.008/011 (n = 2), A.Br.005/006 (n = 2) and A.Br.Aust94 (n = 1). The match with the A.Br.Ames lineage is of particular interest as the occurrence of such lineage in Europe is demonstrated for the first time, filling an historical gap within the phylogeography of the lineage. Comparative genome analyses of these strains with 41 isolates from other parts of the world revealed that the two Danish A.Br.008/011 strains were related to the heroin-associated strains responsible for outbreaks of injection anthrax in drug users in Europe. Eight novel diagnostic SNPs that specifically discriminate the different sub-groups of Danish strains were identified and developed into PCR-based genotyping assays. PMID:26317972

  3. Abnormal auditory forward masking pattern in the brainstem response of individuals with Asperger syndrome

    PubMed Central

    Källstrand, Johan; Olsson, Olle; Nehlstedt, Sara Fristedt; Sköld, Mia Ling; Nielzén, Sören

    2010-01-01

    Abnormal auditory information processing has been reported in individuals with autism spectrum disorders (ASD). In the present study auditory processing was investigated by recording auditory brainstem responses (ABRs) elicited by forward masking in adults diagnosed with Asperger syndrome (AS). Sixteen AS subjects were included in the forward masking experiment and compared to three control groups consisting of healthy individuals (n = 16), schizophrenic patients (n = 16) and attention deficit hyperactivity disorder patients (n = 16), respectively, of matching age and gender. The results showed that the AS subjects exhibited abnormally low activity in the early part of their ABRs that distinctly separated them from the three control groups. Specifically, wave III amplitudes were significantly lower in the AS group than for all the control groups in the forward masking condition (P < 0.005), which was not the case in the baseline condition. Thus, electrophysiological measurements of ABRs to complex sound stimuli (eg, forward masking) may lead to a better understanding of the underlying neurophysiology of AS. Future studies may further point to specific ABR characteristics in AS individuals that separate them from individuals diagnosed with other neurodevelopmental diseases. PMID:20628629

  4. Physical mapping of chromosome 17p13.3 in the region of a putative tumor suppressor gene important in medulloblastoma

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

    McDonald, J.D.; Daneshvar, L.; Willert, J.R.

    1994-09-01

    Deletion mapping of a medulloblastoma tumor panel revealed loss of distal chromosome 17p13.3 sequences in tumors from 14 of 32 patients (44%). Of the 14 tumors showing loss of heterozygosity by restriction fragment length polymorphism analysis, 14 of 14 (100%) displayed loss of the telomeric marker p144-D6 (D17S34), while a probe for the ABR gene on 17p13.3 was lost in 7 of 8 (88%) informative cases. Using pulsed-field gel electrophoresis, we localized the polymorphic marker (VNTR-A) of the ABR gene locus to within 220 kb of the p144-D6 locus. A cosmid contig constructed in this region was used to demonstratemore » by fluorescence in situ hybridization that the ABR gene is oriented transcriptionally 5{prime} to 3{prime} toward the telomere. This report provides new physical mapping data for the ABR gene, which has not been previously shown to be deleted in medulloblastoma. These results provide further evidence for the existence of a second tumor suppressor gene distinct from p53 on distal chromosome 17p. 12 refs., 3 figs.« less

  5. Auditory brainstem response screening for hearing loss in high risk neonates.

    PubMed

    Watson, D R; McClelland, R J; Adams, D A

    1996-07-01

    The present paper reports the findings of a 7 year study evaluating the use of the auditory brainstem response (ABR) as the basis of a hearing screening procedure in a group of newborns at increased risk of hearing impairment. A Special Care Baby Unit (SCBU) population of 417 infants with diverse clinical backgrounds and treatment histories was tested for hearing impairment at birth using ABR audiometry. Some 332 passed the original screen at 30 dBnHL test level in both ears. Of the failure group, 18 did not survive and 32 had some degree of hearing impairment confirmed, nine of which were sensorineural in origin. An increased incidence of persistent middle ear disease was also noted in the failure group. A detailed operational analysis demonstrates that provided appropriate pass/fail criteria are adopted, the ABR technique offers excellent sensitivity and specificity for the detection of significant hearing loss in the test population. Furthermore, the study establishes that implementation of an ABR-based screening programme could reduce the average age at detection of permanent hearing loss by 7 months. A cost assessment shows that the introduction of such a targetted screening procedure could be done at a reasonable outlay.

  6. Precocious hearing in harbour porpoise neonates.

    PubMed

    Wahlberg, Magnus; Delgado-García, Lara; Kristensen, Jakob H

    2017-02-01

    Hearing is the primary sensory modality for toothed whales, but it is not known at which age it is fully developed. For newborn calves, hearing could fill an important function in maintaining contact with the mother and to develop echolocation skills. We non-invasively measured the auditory brainstem response (ABR) in two neonate (age 1-4 days) and three adult harbour porpoises (Phocoena phocoena). The stimuli consisted of clicks centred at 130 kHz, which is within the frequency band used for echolocation and communication in this species. The temporal pattern of the neonate ABRs was indistinguishable to the adult ones. There were no significant differences between calves and adults regarding hearing thresholds and ABR latencies. The ABR amplitudes were up to more than an order of magnitude larger in newborns than in adults, most likely due to the neonates' smaller size. These results indicate that hearing is fully developed within a day after birth, which suggests that harbour porpoise neonates have the earliest hearing development of any mammal studied so far. This may be explained by the evolutionary pressures imposed by the aquatic environment for a rapid development of the key sensory system in harbour porpoises.

  7. Association of Access to Publicly Funded Family Planning Services With Adolescent Birthrates in California Counties

    PubMed Central

    Chabot, Marina J.; Navarro, Sandy; Swann, Diane; Darney, Philip; Thiel de Bocanegra, Heike

    2014-01-01

    Objectives. We examined the association of adolescent birthrates (ABRs) with access to and receipt of publicly funded family planning services in California counties provided through 2 state programs: Medi-Cal, California’s Medicaid program, and the Family Planning, Access, Care, and Treatment (Family PACT) program. Methods. Our key data sources included the California Health Interview Survey and California Women’s Health Survey, Medi-Cal and Family PACT claims data, and the Birth Statistical Master File. We constructed a linear regression analysis measuring the relationship of access to and receipt of family planning services with ABRs when controlling for counties’ select covariates. Results. The regression analysis indicated that a higher access rate to Family PACT in a county was associated with a lower ABR (B = −0.19; P < .01) when controlling for unemployment rate, percentage of foreign-born adolescents, and percentage of adult low-income births. Conclusions. Efforts to reduce ABRs, specifically in counties that had persistently high rates are critical to achieving a healthy future for the state and the nation. Family PACT played a crucial role in helping adolescents avoid unintended and early childbearing. PMID:24354841

  8. [The characteristics of auditory brainstem response in preterm very low birth weight babies].

    PubMed

    Wang, Xiaoya; Luo, Renzhong; Wen, Ruijin; Chen, Qian; Zhou, Jialin; Zou, Yu

    2009-08-01

    To discuss the characteristics of auditory brainstem response in preterm very low birth weight (VLBW) babies and to investigate the correlations between the ABR and clinical characteristics. Fifty-nine VLBW babies (118 ears) were enrolled in the study and 30 term normal babies as the control group. Tympanometry, acoustic reflex, DPOAE, ABR were obtained in all the babies. The prevalence of hearing loss in VLBW babies was higher than normal term babies and babies with perinatal complications higher than those without perinatal complications. There was no correlations between ABR threshold and gestational age, birth weight, postconceptional age, negative correlations between wave I, III and V latencies I - III, III - V and I - V intervals and postconceptional age. Wave I and V latencies, I - III and III - V intervals differed significantly between the two groups. The perinatal complications were the most important causes of the hearing loss in preterm VLBW babies than the gestational age and birth weight. There was a high prevalence of peripheral hearing loss in the preterm VLBW babies. Combining OAE and automated ABR should be applied for hearing screening. Regular follow-up was very important in all the preterm VLBW neonatal.

  9. Temporary Hearing Threshold Shift in Healthy Volunteers with Hearing Protection Caused by Acoustic Noise Exposure during 3-T Multisequence MR Neuroimaging.

    PubMed

    Jin, Chao; Li, Huan; Li, Xianjun; Wang, Miaomiao; Liu, Congcong; Guo, Jianxin; Yang, Jian

    2018-02-01

    Purpose To determine whether a single 51-minute exposure to acoustic noise during 3-T multisequence magnetic resonance (MR) neuroimaging could affect the hearing threshold of healthy adults with earplugs and sponge mats as hearing protection. Materials and Methods With earplugs and motion-refraining sponge mats as hearing protection, 26 healthy young adults underwent 3-T MR neuroimaging imaging that included T1-weighted three-dimensional gradient-echo sequence, T2-weighted fast spin-echo sequence, diffusion-tensor imaging, diffusion-kurtosis imaging, T2*-weighted three-dimensional multiecho gradient-echo sequence, and blood oxygen level-dependent imaging. Automated auditory brainstem response (ABR) was used to measure the hearing thresholds within 24 hours before, within 20 minutes after, and 25 days after the MR examination. One-way repeated-measure analysis of variance with Bonferroni adjustment was used to compare automated ABR results among the three tests and partial η 2 (η p 2 ) was reported as a measure of effect size. Results Automated ABR results showed significantly increased mean threshold shift of 5.0 dB ± 8.1 (standard deviation) (left ear: 4.8 dB ± 9.2 [95% confidence interval: 1.09, 8.53], η p 2 = 0.221, P = .013; right ear: 5.2 dB ± 6.9 [95% confidence interval: 2.36, 8.02], η p 2 = 0.364, P = .001) immediately after the MR examination compared with the baseline study. This shift is below the temporary threshold shift of 40-50 dB that is associated with cochlea nerve changes. Automated ABR obtained at day 25 after MR imaging showed no significant differences from baseline (left ear: -2.3 dB ± 8.6 [95% confidence interval: -5.79, 1.78], η p 2 = 0.069, P = .185; right ear: 0.4 dB ± 7.3 [95% confidence interval: -3.35, 2.58], η p 2 = 0.003, P = .791). Conclusion A 3-T MR neuroimaging examination with the acoustic noise at equivalent sound pressure level of 103.5-111.3 dBA lasting 51 minutes can cause temporary hearing threshold shift in healthy volunteers with hearing protection. © RSNA, 2017.

  10. [Vestibulo-cochlear disturbances in the course of vaso-neural conflict of vestibule-cochlear nerve--diagnostic and therapeutic problems].

    PubMed

    Orendorz-Fraczkowska, Krystyna; Jaworska, Marzena; Gawron, Wojciech; Badowski, Roman; Nadolska, Beata

    2007-01-01

    Symptoms encompassing sensorineural hearing loss, tinnitus and vertigo occur in many diseases of various origin. The diagnostics in such cases is especially difficult and often requires interdisciplinary cooperation. Despite of that many cases remain unexplained. The two cases with above mentioned symptoms (52 year-old woman and 46 year-old man) with differentiated clinical course were presented. The woman for one year experienced left sided, extreme tinnitus with paroxysmal vertigo and dizziness. The man with sudden monolateral hearing loss and tinnitus that disappeared after corticosteroid therapy, complained about recurrence of fluctuating hearing loss and tinnitus accompanied by chronic instability. The diagnostics of hearing and balance organs was performed (pure tone audiometry, impedance audiometry, DPOAE, ABR, ENG) complemented with computed tomography and Nuclear Resonance. Female patient presented bilateral mild sensorineural hearing loss, more intensive on the left side, male patient right sided sensorineural hearing loss in the frequencies from 250 to 1500 Hz. The elongation of some peak values in ABR test (with bilaterally proper otoacoustic emissions) as well as partial canal paresis on the hearing loss side suggested primary diagnosis of neoplasmatic process. It was an indication to perform radiological diagnostics. The radiologic findings revealed the contact of vestibulo-cochlear nerve with the loop of cerebellar inferior anterior artery within the internal acoustic canal. The course of the disease and diagnostic tests do not provide characteristic data that let diagnose neuro-vascular conflict. One has to be aware of such possibility in patients with intensive vertigo and dizziness that do not improve after treatment when other causes do not justify the symptoms.

  11. 48 CFR 702.170-4 - Cooperating country.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Cooperating country. 702.170-4 Section 702.170-4 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL DEVELOPMENT GENERAL DEFINITIONS OF WORDS AND TERMS Definitions 702.170-4 Cooperating country. Cooperating country...

  12. Rescue of Outer Hair Cells with Antisense Oligonucleotides in Usher Mice Is Dependent on Age of Treatment.

    PubMed

    Ponnath, Abhilash; Depreux, Frederic F; Jodelka, Francine M; Rigo, Frank; Farris, Hamilton E; Hastings, Michelle L; Lentz, Jennifer J

    2018-02-01

    The absence of functional outer hair cells is a component of several forms of hereditary hearing impairment, including Usher syndrome, the most common cause of concurrent hearing and vision loss. Antisense oligonucleotide (ASO) treatment of mice with the human Usher mutation, Ush1c c.216G>A, corrects gene expression and significantly improves hearing, as measured by auditory-evoked brainstem responses (ABRs), as well as inner and outer hair cell (IHC and OHC) bundle morphology. However, it is not clear whether the improvement in hearing achieved by ASO treatment involves the functional rescue of outer hair cells. Here, we show that Ush1c c.216AA mice lack OHC function as evidenced by the absence of distortion product otoacoustic emissions (DPOAEs) in response to low-, mid-, and high-frequency tone pairs. This OHC deficit is rescued by treatment with an ASO that corrects expression of Ush1c c.216G>A. Interestingly, although rescue of inner hairs cells, as measured by ABR, is achieved by ASO treatment as late as 7 days after birth, rescue of outer hair cells, measured by DPOAE, requires treatment before post-natal day 5. These results suggest that ASO-mediated rescue of both IHC and OHC function is age dependent and that the treatment window is different for the different cell types. The timing of treatment for congenital hearing disorders is of critical importance for the development of drugs such ASO-29 for hearing rescue.

  13. 48 CFR 225.7902 - Defense Trade Cooperation Treaties.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Defense Trade Cooperation Treaties. 225.7902 Section 225.7902 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION EXPORT CONTROL 225.7902 Defense Trade Cooperation Treaties. This...

  14. 48 CFR 225.7902 - Defense Trade Cooperation Treaties.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Defense Trade Cooperation Treaties. 225.7902 Section 225.7902 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION EXPORT CONTROL 225.7902 Defense Trade Cooperation Treaties. This...

  15. 78 FR 20662 - Preparation for International Cooperation on Cosmetics Regulation; Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-05

    ...] Preparation for International Cooperation on Cosmetics Regulation; Public Meeting AGENCY: Food and Drug... public meeting entitled, ``International Cooperation on Cosmetics Regulation (ICCR)--Preparation for ICCR... Maria Rossana (Rosemary) Cook (see Contact Person) by May 1, 2013. You may present data, information, or...

  16. 77 FR 14405 - Preparation for International Cooperation on Cosmetics Regulations; Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-09

    ...] Preparation for International Cooperation on Cosmetics Regulations; Public Meeting AGENCY: Food and Drug... public meeting entitled ``International Cooperation on Cosmetics Regulations (ICCR)-Preparation for ICCR.... Interested persons may present data, information, or views orally or in writing, on issues pending at the...

  17. Evolution of amoxicillin/clavulanate in the treatment of adults with acute bacterial rhinosinusitis and community-acquired pneumonia in response to antimicrobial-resistance patterns.

    PubMed

    File, Thomas M; Benninger, Michael S; Jacobs, Michael R

    2004-06-01

    Current treatment guidelines for community-acquired respiratory tract infections no longer depend solely on the characteristics of the patient and the clinical syndrome, but on those of the offending pathogen, including presence and level of antimicrobial resistance. The most common respiratory tract pathogens known to cause acute bacterial rhinosinusitis (ABRS) and community-acquired pneumonia (CAP) include Streptococcus pneumoniae and Haemophilus influenzae. The prevalence of antimicrobial resistance, especially b-lactum and macrolide resistance, among S pneumoniae and H influenzae has increased dramatically during the past 2 decades, diminishing the activity of many older antimicrobials against resistant organisms. A pharmacokinetically enhanced formulation of amoxicillin/clavulanate has been developed to fulfill the need for an oral b-lactam antimicrobial that achieves a greater time that the serum drug concentration exceeds the minimum inhibitory concentration (T > MIC) of antimicrobials against pathogens than conventional formulations to improve activity against S pneumoniae with reduced susceptibility to penicillin. The b-lactamase inhibitor clavulanate allows for coverage of b-lactamase-producing pathogens, such as H influenzae and M catarrhalis. This article reviews the rationale for, and evolution of, oral amoxicillin clavulanate for ABRS and CAP

  18. NREL Energy Storage Projects. FY2014 Annual Report

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

    Pesaran, Ahmad; Ban, Chunmei; Burton, Evan

    2015-03-01

    The National Renewable Energy Laboratory supports energy storage R&D under the Office of Vehicle Technologies at the U.S. Department of Energy. The DOE Energy Storage Program’s charter is to develop battery technologies that will enable large market penetration of electric drive vehicles. These vehicles could have a significant impact on the nation’s goal of reducing dependence on imported oil and gaseous pollutant emissions. DOE has established several program activities to address and overcome the barriers limiting the penetration of electric drive battery technologies: cost, performance, safety, and life. These programs are; Advanced Battery Development through the United States Advanced Batterymore » Consortium (USABC); Battery Testing, Analysis, and Design; Applied Battery Research (ABR); and Focused Fundamental Research, or Batteries for Advanced Transportation Technologies (BATT) In FY14, DOE funded NREL to make technical contributions to all of these R&D activities. This report summarizes NREL’s R&D projects in FY14 in support of the USABC; Battery Testing, Analysis, and Design; ABR; and BATT program elements. The FY14 projects under NREL’s Energy Storage R&D program are briefly described below. Each of these is discussed in depth in this report.« less

  19. Adenosine receptors regulate susceptibility to noise-induced neural injury in the mouse cochlea and hearing loss.

    PubMed

    Vlajkovic, Srdjan M; Ambepitiya, Kaushi; Barclay, Meagan; Boison, Detlev; Housley, Gary D; Thorne, Peter R

    2017-03-01

    Our previous studies have shown that the stimulation of A 1 adenosine receptors in the inner ear can mitigate the loss of sensory hair cells and hearing loss caused by exposure to traumatic noise. Here, we focus on the role of adenosine receptors (AR) in the development of noise-induced neural injury in the cochlea using A 1 AR and A 2A AR null mice (A 1 AR -/- and A 2A AR -/- ). Wildtype (WT) and AR deficient mice were exposed to octave band noise (8-16 kHz, 100 dB SPL) for 2 h to induce cochlear injury and hearing loss. Auditory thresholds and input/output functions were assessed using auditory brainstem responses (ABR) before and two weeks post-exposure. The loss of outer hair cells (OHC), afferent synapses and spiral ganglion neurons (SGN) were assessed by quantitative histology. A 1 AR -/- mice (6-8 weeks old) displayed a high frequency hearing loss (ABR threshold shift and reduced ABR wave I and II amplitudes). This hearing loss was further aggravated by acute noise exposure and exceeded the hearing loss in the WT and A 2A AR -/- mice. All mice experienced the loss of OHC, synaptic ribbons and SGN after noise exposure, but the loss of SGN was significantly higher in A 1 AR -/- mice than in the A 2A AR -/- and WT genotypes. The A 2A AR -/- demonstrated better preservation of OHC and afferent synapses and the minimal loss of SGN after noise exposure. The findings suggest that the loss of A 1 AR expression results in an increased susceptibility to cochlear neural injury and hearing loss, whilst absence of A 2A AR increases cochlear resistance to acoustic trauma. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. TNF-α inhibition using etanercept prevents noise-induced hearing loss by improvement of cochlear blood flow in vivo.

    PubMed

    Arpornchayanon, Warangkana; Canis, Martin; Ihler, Friedrich; Settevendemie, Claudia; Strieth, Sebastian

    2013-08-01

    Exposure to loud noise can impair cochlear microcirculation and cause noise-induced hearing loss (NIHL). TNF-α signaling has been shown to be activated in NIHL and to control spiral modiolar artery vasoconstriction that regulates cochlear microcirculation. It was the aim of this experimental study to analyse the effects of the TNF-α inhibitor etanercept on cochlear microcirculation and hearing threshold shift in NIHL in vivo. After assessment of normacusis using ABR, loud noise (106 dB SPL, 30 minutes) was applied on both ears in guinea pigs. Etanercept was administered systemically after loud noise exposure while control animals received a saline solution. In vivo fluorescence microscopy of strial capillaries was performed after surgical exposure of the cochlea for microcirculatory analysis. ABR measurements were derived from the contralateral ear. Guinea pigs (n = 6, per group). Compared to controls, cochlear blood flow in strial capillary segments was significantly increased in etanercept-treated animals. Additionally, hearing threshold was preserved in animals receiving the TNF-α inhibitor in contrast to a significant threshold raising in controls. TNF-α inhibition using etanercept improves cochlear microcirculation and protects hearing levels after loud noise exposure and appears as a promising treatment strategy for human NIHL.

  1. Abnormally banded chromosomal regions in doxorubicin-resistant B16-BL6 murine melanoma cells.

    PubMed

    Slovak, M L; Hoeltge, G A; Ganapathi, R

    1986-08-01

    B16-BL6 murine melanoma cells were selected for cytogenetic evaluation during the stepwise development of increasing resistance in vitro to the antitumor antibiotic, doxorubicin (DOX). Karyotypic studies demonstrated extensive heteroploidy with both numerical and structural abnormalities which were not present in the parental DOX-sensitive B16-BL6 cells. Trypsin-Giemsa banding revealed the presence of several marker chromosomes containing abnormally banding regions (ABRs) in the 44-fold B16-BL6 DOX-resistant subline. These ABRs appeared to be more homogeneously staining at the higher DOX concentrations. Length measurements (ABR index) in seven banded metaphases indicated a direct correlation with increasing DOX concentration. When the DOX-resistant cells were grown in drug-free medium for 1 yr, the drug-resistant phenotype gradually declined in parallel with the level of resistance and the ABR index. DOX-induced cytogenetic damage examined by sister chromatid exchange methodology in parental B16-BL6 cells indicated a linear sister chromatid exchange:DOX dose-response relationship. However, after continuous treatment of parental B16-BL6 cells with DOX (0.01 microgram/ml) for 30 days, sister chromatid exchange scores were found to return to base-line values. The B16-BL6 resistant cells demonstrated a cross-resistant phenotype with N-trifluoroacetyladriamycin-14-valerate, actinomycin D, and the Vinca alkaloids but not with 1-beta-D-arabinofuranosylcytosine. The results suggest that ABR-containing chromosomes in DOX-resistant sublines may represent cytogenetic alterations of specific amplified genes involved in the expression of DOX resistance. Further studies are required to identify and define the possible gene products and to correlate their relationship to the cytotoxic action of doxorubicin.

  2. Neonate Auditory Brainstem Responses to CE-Chirp and CE-Chirp Octave Band Stimuli II: Versus Adult Auditory Brainstem Responses.

    PubMed

    Cobb, Kensi M; Stuart, Andrew

    The purpose of the study was to examine the differences in auditory brainstem response (ABR) latency and amplitude indices to the CE-Chirp stimuli in neonates versus young adults as a function of stimulus level, rate, polarity, frequency and gender. Participants were 168 healthy neonates and 20 normal-hearing young adults. ABRs were obtained to air- and bone-conducted CE-Chirps and air-conducted CE-Chirp octave band stimuli. The effects of stimulus level, rate, and polarity were examined with air-conducted CE-Chirps. The effect of stimulus level was also examined with bone-conducted CE-Chirps and CE-Chirp octave band stimuli. The effect of gender was examined across all stimulus manipulations. In general, ABR wave V amplitudes were significantly larger (p < 0.0001) and latencies were significantly shorter (p < 0.0001) for adults versus neonates for all air-conducted CE-Chirp stimuli with all stimulus manipulations. For bone-conducted CE-Chirps, infants had significantly shorter wave V latencies than adults at 15 dB nHL and 45 dB nHL (p = 0.02). Adult wave V amplitude was significantly larger for bone-conducted CE-Chirps only at 30 dB nHL (p = 0.02). The effect of gender was not statistically significant across all measures (p > 0.05). Significant differences in ABR latencies and amplitudes exist between newborns and young adults using CE-Chirp stimuli. These differences are consistent with differences to traditional click and tone burst stimuli and reflect maturational differences as a function of age. These findings continue to emphasize the importance of interpreting ABR results using age-based normative data.

  3. The ototoxic effect of boric acid solutions applied into the middle ear of guinea pigs.

    PubMed

    Oztürkcan, Sedat; Dündar, Riza; Katilmis, Hüseyin; Ilknur, Ali Ekber; Aktaş, Sinem; Haciömeroğlu, Senem

    2009-05-01

    This study analyzed the ototoxic effects of boric acid solutions. Boric acid solutions have been used as otologic preparations for many years. Boric acid is commonly found in solutions prepared with alcohol or distilled water but can also be found in a powder form. These preparations are used for both their antiseptic and acidic qualities in external and middle ear infections. We investigated the ototoxic effect of boric acid solutions on guinea pigs. We are unaware of any similar, previously published study of this subject in English. The study was conducted on 28 young albino guinea pigs. Prior to application of the boric acid solution under general anesthesia, an Auditory Brainstem Response (ABRs) test was applied to the right ear of the guinea pigs. Following the test, a perforation was created on the tympanic membrane of the right ear of each guinea pig and small gelfoam pieces were inserted into the perforated area. Test solutions were administered to the middle ear for 10 days by means of a transcanal route. Fifteen days after inserting the gelfoams in all of the guinea pigs, we anasthesized the guinea pigs and removed the gelfoams from the perforated region of the ear and then performed an ABRs on each guinea pig. The ABRs were within the normal range before the applications. After the application, no significant changes were detected in the ABRs thresholds in neither the saline group nor the group administered boric acid and distilled water solution; however, significant changes were detected in the ABRs thresholds of the Gentamicine and boric acid and alcohol solution groups. We believe that a 4% boric acid solution prepared with distilled water can be a more reliable preparation than a 4% boric acid solution prepared with alcohol.

  4. Benign paroxysmal vertigo of childhood: diagnostic value of vestibular test and high stimulus rate auditory brainstem response test.

    PubMed

    Zhang, Daogong; Fan, Zhaomin; Han, Yuechen; Wang, Mingming; Xu, Lei; Luo, Jianfen; Ai, Yu; Wang, Haibo

    2012-01-01

    To investigate the diagnostic value of vestibular test and high stimulus rate auditory brainstem response (ABR) test and the possible mechanism responsible for benign paroxysmal vertigo of childhood (BPVC). Data of 56 patients with BPVC in vertigo clinic of our hospital from May 2007 to September 2008 were retrospectively analyzed in this study. Patients with BPVC were tested with pure tone audiometry, high stimulus rate auditory brainstem response test (ABR), transcranial Doppler sonography (TCD), bithermal caloric test, and VEMP. The results of the hearing and vestibular function test were compared and analyzed. There were 56 patients with BPVC, including 32 men, 24 women, aged 3-12 years old, with an average of 6.5 years. Among 56 cases of BPVC patients, the results of pure tone audiometry were all normal. High stimulus rate ABR was abnormal in 66.1% (37/56) of cases. TCD showed 57.1% abnormality in 56 cases, including faster flow rate in 28 cases and slower flow rate in 4 cases. High stimulus rate ABR and TCD were both abnormal in 48.2% (27/56) of cases. Bithermal caloric test was abnormal in 14.3% (8/56) of cases. VEMP showed 32.1% abnormality, including amplitude abnormality in 16 cases and latency abnormality in 2 cases. The abnormal rate of VEMP was much higher than that of caloric test. Vascular mechanisms might be involved in the pathogenesis of BPVC and there is strong evidence for close relationship between BPVC and migraine. High stimulus rate ABR is helpful in the diagnosis of BPVC. The inferior vestibular pathway is much more impaired than the superior vestibular pathway in BPVC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Dual DNA binding property of ABA insensitive 3 like factors targeted to promoters responsive to ABA and auxin.

    PubMed

    Nag, Ronita; Maity, Manas Kanti; Dasgupta, Maitrayee

    2005-11-01

    The ABA responsive ABI3 and the auxin responsive ARF family of transcription factors bind the CATGCATG (Sph) and TGTCTC core motifs in ABA and auxin response elements (ABRE and AuxRE), respectively. Several evidences indicate ABI3s to act downstream to auxin too. Because DNA binding domain of ABI3s shows significant overlap with ARFs we enquired whether auxin responsiveness through ABI3s could be mediated by their binding to canonical AuxREs. Investigations were undertaken through in vitro gel mobility shift assays (GMSA) using the DNA binding domain B3 of PvAlf (Phaseolus vulgaris ABI3 like factor) and upstream regions of auxin responsive gene GH3 (-267 to -141) and ABA responsive gene Em (-316 to -146) harboring AuxRE and ABRE, respectively. We demonstrate that B3 domain of PvAlf could bind AuxRE only when B3 was associated with its flanking domain B2 (B2B3). Such strict requirement of B2 domain was not observed with ABRE, where B3 could bind with or without being associated with B2. This dual specificity in DNA binding of ABI3s was also demonstrated with nuclear extracts of cultured cells of Arachis hypogea. Supershift analysis of ABRE and AuxRE bound nuclear proteins with antibodies raised against B2B3 domains of PvAlf revealed that ABI3 associated complexes were detectable in association with both cis elements. Competition GMSA confirmed the same complexes to bind ABRE and AuxRE. This dual specificity of ABI3 like factors in DNA binding targeted to natural promoters responsive to ABA and auxin suggests them to have a potential role in conferring crosstalk between these two phytohormones.

  6. The value of ASSR threshold-based bilateral hearing aid fitting in children with difficult or unreliable behavioral audiometry.

    PubMed

    Vlastarakos, Petros V; Vasileiou, Alexandra; Nikolopoulos, Thomas P

    2017-12-01

    We conducted an analysis to assess the relative contribution of auditory brainstem response (ABR) testing and auditory steady-state response (ASSR) testing in providing appropriate hearing aid fitting in hearing-impaired children with difficult or unreliable behavioral audiometry. Of 150 infants and children who had been referred to us for hearing assessment as part of a neonatal hearing screening and cochlear implantation program, we identified 5 who exhibited significant discrepancies between click-ABR and ASSR testing results and difficult or unreliable behavioral audiometry. Hearing aid fitting in pediatric cochlear implant candidates for a trial period of 3 to 6 months is a common practice in many implant programs, but monitoring the progress of the amplified infants and providing appropriate hearing aid fitting can be challenging. If we accept the premise that we can assess the linguistic progress of amplified infants with an acceptable degree of certainty, the auditory behavior that we are monitoring presupposes appropriate bilateral hearing aid fitting. This may become very challenging in young children, or even in older children with difficult or unreliable behavioral audiometry results. This challenge can be addressed by using data from both ABR and ASSR testing. Fitting attempts that employ data from only ABR testing provide amplification that involves the range of spoken language but is not frequency-specific. Hearing aid fitting should also incorporate and take into account ASSR data because reliance on ABR testing alone might compromise the validity of the monitoring process. In conclusion, we believe that ASSR threshold-based bilateral hearing aid fitting is necessary to provide frequency-specific amplification of hearing and appropriate propulsion in the prelinguistic vocalizations of monitored infants.

  7. Increased anesthesia time using 2,2,2-tribromoethanol-chloral hydrate with low impact on mouse psychoacoustics.

    PubMed

    Maheras, Kathleen J; Gow, Alexander

    2013-09-30

    To examine psychoacoustics in mice, we have used 2,2,2-tribromoethanol anesthesia in multiple studies. We find this drug is fast-acting and yields consistent results, providing 25-30 min of anesthesia. Our recent studies in binaural hearing prompted development of a regimen to anesthesia time to 1h. We tested a novel cocktail using 2,2,2-tribromoethanol coupled with low dose chloral hydrate to extend the effective anesthesia time. We have established an intraperitoneal dosing regimen for 2,2,2-tribromoethanol-chloral hydrate anesthesia. To measure efficacy of the drug cocktail, we measured auditory brainstem responses (ABRs) at 10 min intervals to determine the effects on hearing thresholds and wave amplitudes and latencies. This novel drug combination increases effective anesthesia to 1h. ABR Wave I amplitudes, but not latencies, are marginally suppressed. Additionally, amplitudes of the centrally derived Waves III and V show significant inter-animal variability that is independent of stimulus intensity. These data argue against the systematic suppression of ABRs by the drug cocktail. Using 2,2,2-tribromoethanol-chloral hydrate combination in psychoacoustic studies has several advantages over other drug cocktails, the most important being preservation of latencies from centrally- and peripherally-derived ABR waves. In addition, hearing thresholds are unchanged and wave amplitudes are not systematically suppressed, although they exhibit greater variability. We demonstrate that 375 mg/kg 2,2,2-tribromoethanol followed after 5 min by 200mg/kg chloral hydrate provides an anesthesia time of 60 min, has negligible effects on ABR wave latencies and thresholds and non-systematic effects on amplitudes. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Increased Anesthesia Time Using 2,2,2-tribromoethanol-Chloral Hydrate With Low Impact On Mouse Psychoacoustics

    PubMed Central

    Maheras, Kathleen J.; Gow, Alexander

    2013-01-01

    Background To examine psychoacoustics in mice, we have used 2,2,2-tribromoethanol anesthesia in multiple studies. We find this drug is fast-acting and yields consistent results, providing 30 – 40 min of anesthesia. Our recent studies in binaural hearing prompted development of a regimen to anesthesia time to one hour. We tested a novel cocktail using 2,2,2-tribromoethanol coupled with low dose chloral hydrate to extend the effective anesthesia time. New Method We have established an intraperitoneal dosing regimen for 2,2,2-tribromoethanol-chloral hydrate anesthesia. To measure efficacy of the drug cocktail, we measured auditory brainstem responses (ABRs) at 10 min intervals to determine the effects on hearing thresholds and wave amplitudes and latencies. Results This novel drug combination increases effective anesthesia to one hour. ABR Wave I amplitudes, but not latencies, are marginally suppressed. Additionally, amplitudes of the centrally-derived Waves III and V show significant inter-animal variability that is independent of stimulus intensity. These data argue against the systematic suppression of ABRs by the drug cocktail. Comparison with Existing Methods Using 2,2,2-tribromoethanol-chloral hydrate combination in psychoacoustic studies has several advantages over other drug cocktails, the most important being preservation of latencies from centrally- and peripherally-derived ABR waves. In addition, hearing thresholds are unchanged and wave amplitudes are not systematically suppressed, although they exhibit greater variability. Conclusions We demonstrate that 375 mg/kg 2,2,2-tribromoethanol followed after five min by 200 mg/kg chloral hydrate provides an anesthesia time of 60 min, has negligible effects on ABR wave latencies and thresholds and non-systematic effects on amplitudes. PMID:23856212

  9. Automatic quality assessment and peak identification of auditory brainstem responses with fitted parametric peaks.

    PubMed

    Valderrama, Joaquin T; de la Torre, Angel; Alvarez, Isaac; Segura, Jose Carlos; Thornton, A Roger D; Sainz, Manuel; Vargas, Jose Luis

    2014-05-01

    The recording of the auditory brainstem response (ABR) is used worldwide for hearing screening purposes. In this process, a precise estimation of the most relevant components is essential for an accurate interpretation of these signals. This evaluation is usually carried out subjectively by an audiologist. However, the use of automatic methods for this purpose is being encouraged nowadays in order to reduce human evaluation biases and ensure uniformity among test conditions, patients, and screening personnel. This article describes a new method that performs automatic quality assessment and identification of the peaks, the fitted parametric peaks (FPP). This method is based on the use of synthesized peaks that are adjusted to the ABR response. The FPP is validated, on one hand, by an analysis of amplitudes and latencies measured manually by an audiologist and automatically by the FPP method in ABR signals recorded at different stimulation rates; and on the other hand, contrasting the performance of the FPP method with the automatic evaluation techniques based on the correlation coefficient, FSP, and cross correlation with a predefined template waveform by comparing the automatic evaluations of the quality of these methods with subjective evaluations provided by five experienced evaluators on a set of ABR signals of different quality. The results of this study suggest (a) that the FPP method can be used to provide an accurate parameterization of the peaks in terms of amplitude, latency, and width, and (b) that the FPP remains as the method that best approaches the averaged subjective quality evaluation, as well as provides the best results in terms of sensitivity and specificity in ABR signals validation. The significance of these findings and the clinical value of the FPP method are highlighted on this paper. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Effect of hearing aids on auditory function in infants with perinatal brain injury and severe hearing loss.

    PubMed

    Moreno-Aguirre, Alma Janeth; Santiago-Rodríguez, Efraín; Harmony, Thalía; Fernández-Bouzas, Antonio

    2012-01-01

    Approximately 2-4% of newborns with perinatal risk factors present with hearing loss. Our aim was to analyze the effect of hearing aid use on auditory function evaluated based on otoacoustic emissions (OAEs), auditory brain responses (ABRs) and auditory steady state responses (ASSRs) in infants with perinatal brain injury and profound hearing loss. A prospective, longitudinal study of auditory function in infants with profound hearing loss. Right side hearing before and after hearing aid use was compared with left side hearing (not stimulated and used as control). All infants were subjected to OAE, ABR and ASSR evaluations before and after hearing aid use. The average ABR threshold decreased from 90.0 to 80.0 dB (p = 0.003) after six months of hearing aid use. In the left ear, which was used as a control, the ABR threshold decreased from 94.6 to 87.6 dB, which was not significant (p>0.05). In addition, the ASSR threshold in the 4000-Hz frequency decreased from 89 dB to 72 dB (p = 0.013) after six months of right ear hearing aid use; the other frequencies in the right ear and all frequencies in the left ear did not show significant differences in any of the measured parameters (p>0.05). OAEs were absent in the baseline test and showed no changes after hearing aid use in the right ear (p>0.05). This study provides evidence that early hearing aid use decreases the hearing threshold in ABR and ASSR assessments with no functional modifications in the auditory receptor, as evaluated by OAEs.

  11. Effect of Hearing Aids on Auditory Function in Infants with Perinatal Brain Injury and Severe Hearing Loss

    PubMed Central

    Moreno-Aguirre, Alma Janeth; Santiago-Rodríguez, Efraín; Harmony, Thalía; Fernández-Bouzas, Antonio

    2012-01-01

    Background Approximately 2–4% of newborns with perinatal risk factors present with hearing loss. Our aim was to analyze the effect of hearing aid use on auditory function evaluated based on otoacoustic emissions (OAEs), auditory brain responses (ABRs) and auditory steady state responses (ASSRs) in infants with perinatal brain injury and profound hearing loss. Methodology/Principal Findings A prospective, longitudinal study of auditory function in infants with profound hearing loss. Right side hearing before and after hearing aid use was compared with left side hearing (not stimulated and used as control). All infants were subjected to OAE, ABR and ASSR evaluations before and after hearing aid use. The average ABR threshold decreased from 90.0 to 80.0 dB (p = 0.003) after six months of hearing aid use. In the left ear, which was used as a control, the ABR threshold decreased from 94.6 to 87.6 dB, which was not significant (p>0.05). In addition, the ASSR threshold in the 4000-Hz frequency decreased from 89 dB to 72 dB (p = 0.013) after six months of right ear hearing aid use; the other frequencies in the right ear and all frequencies in the left ear did not show significant differences in any of the measured parameters (p>0.05). OAEs were absent in the baseline test and showed no changes after hearing aid use in the right ear (p>0.05). Conclusions/Significance This study provides evidence that early hearing aid use decreases the hearing threshold in ABR and ASSR assessments with no functional modifications in the auditory receptor, as evaluated by OAEs. PMID:22808289

  12. Supra-optimal expression of the cold-regulated OsMyb4 transcription factor in transgenic rice changes the complexity of transcriptional network with major effects on stress tolerance and panicle development.

    PubMed

    Park, Myoung-Ryoul; Yun, Kil-Young; Mohanty, Bijayalaxmi; Herath, Venura; Xu, Fuyu; Wijaya, Edward; Bajic, Vladimir B; Yun, Song-Joong; De Los Reyes, Benildo G

    2010-12-01

    The R2R3-type OsMyb4 transcription factor of rice has been shown to play a role in the regulation of osmotic adjustment in heterologous overexpression studies. However, the exact composition and organization of its underlying transcriptional network has not been established to be a robust tool for stress tolerance enhancement by regulon engineering. OsMyb4 network was dissected based on commonalities between the global chilling stress transcriptome and the transcriptome configured by OsMyb4 overexpression. OsMyb4 controls a hierarchical network comprised of several regulatory sub-clusters associated with cellular defense and rescue, metabolism and development. It regulates target genes either directly or indirectly through intermediary MYB, ERF, bZIP, NAC, ARF and CCAAT-HAP transcription factors. Regulatory sub-clusters have different combinations of MYB-like, GCC-box-like, ERD1-box-like, ABRE-like, G-box-like, as1/ocs/TGA-like, AuxRE-like, gibberellic acid response element (GARE)-like and JAre-like cis-elements. Cold-dependent network activity enhanced cellular antioxidant capacity through radical scavenging mechanisms and increased activities of phenylpropanoid and isoprenoid metabolic processes involving various abscisic acid (ABA), jasmonic acid (JA), salicylic acid (SA), ethylene and reactive oxygen species (ROS) responsive genes. OsMyb4 network is independent of drought response element binding protein/C-repeat binding factor (DREB/CBF) and its sub-regulons operate with possible co-regulators including nuclear factor-Y. Because of its upstream position in the network hierarchy, OsMyb4 functions quantitatively and pleiotrophically. Supra-optimal expression causes misexpression of alternative targets with costly trade-offs to panicle development. © 2010 Blackwell Publishing Ltd.

  13. High-frequency tone burst-evoked ABR latency-intensity functions.

    PubMed

    Fausti, S A; Olson, D J; Frey, R H; Henry, J A; Schaffer, H I

    1993-01-01

    High-frequency tone burst stimuli (8, 10, 12, and 14 kHz) have been developed and demonstrated to provide reliable and valid auditory brainstem responses (ABRs) in normal-hearing subjects. In this study, latency-intensity functions (LIFs) were determined using these stimuli in 14 normal-hearing individuals. Significant shifts in response latency occurred as a function of stimulus intensity for all tone burst frequencies. For each 10 dB shift in intensity, latency shifts for waves I and V were statistically significant except for one isolated instance. LIF slopes were comparable between frequencies, ranging from 0.020 to 0.030 msec/dB. These normal LIFs for high-frequency tone burst-evoked ABRs suggest the degree of response latency change that might be expected from, for example, progressive hearing loss due to ototoxic insult, although these phenomena may not be directly related.

  14. Structural characterization of a novel full-length transcript promoter from Horseradish Latent Virus (HRLV) and its transcriptional regulation by multiple stress responsive transcription factors.

    PubMed

    Khan, Ahamed; Shrestha, Ankita; Bhuyan, Kashyap; Maiti, Indu B; Dey, Nrisingha

    2018-01-01

    The promoter fragment described in this study can be employed for strong transgene expression under both biotic and abiotic stress conditions. Plant-infecting Caulimoviruses have evolved multiple regulatory mechanisms to address various environmental stimuli during the course of evolution. One such mechanism involves the retention of discrete stress responsive cis-elements which are required for their survival and host-specificity. Here we describe the characterization of a novel Caulimoviral promoter isolated from Horseradish Latent Virus (HRLV) and its regulation by multiple stress responsive Transcription factors (TFs) namely DREB1, AREB1 and TGA1a. The activity of full length transcript (Flt-) promoter from HRLV (- 677 to + 283) was investigated in both transient and transgenic assays where we identified H12 (- 427 to + 73) as the highest expressing fragment having ~ 2.5-fold stronger activity than the CaMV35S promoter. The H12 promoter was highly active and near-constitutive in the vegetative and reproductive parts of both Tobacco and Arabidopsis transgenic plants. Interestingly, H12 contains a distinct cluster of cis-elements like dehydration-responsive element (DRE-core; GCCGAC), an ABA-responsive element (ABRE; ACGTGTC) and as-1 element (TGACG) which are known to be induced by cold, drought and pathogen/SA respectively. The specific binding of DREB1, AREB1 and TGA1a to DRE, ABRE and as-1 elements respectively were confirmed by the gel-binding assays using H12 promoter-specific probes. Detailed mutational analysis of the H12 promoter suggested that the presence of DRE-core and as-1 element was indispensable for its activity which was further confirmed by the transactivation assays. Our studies imply that H12 could be a valuable genetic tool for regulated transgene expression under diverse environmental conditions.

  15. The transcription repressor, ZEB1, cooperates with CtBP2 and HDAC1 to suppress IL-2 gene activation in T cells.

    PubMed

    Wang, Jun; Lee, Seungsoo; Teh, Charis En-Yi; Bunting, Karen; Ma, Lina; Shannon, M Frances

    2009-03-01

    Activation of T cells leads to the induction of many cytokine genes that are required for appropriate immune responses, including IL-2, a key cytokine for T cell proliferation and homeostasis. The activating transcription factors such as nuclear factor of activated T cells, nuclear factor kappaB/Rel and activated protein-1 family members that regulate inducible IL-2 gene expression have been well documented. However, negative regulation of the IL-2 gene is less studied. Here we examine the role of zinc finger E-box-binding protein (ZEB) 1, a homeodomain/Zn finger transcription factor, as a repressor of IL-2 gene transcription. We show here that ZEB1 is expressed in non-stimulated and stimulated T cells and using chromatin immunoprecipitation assays we show that ZEB1 binds to the IL-2 promoter. Over-expression of ZEB1 can repress IL-2 promoter activity, as well as endogenous IL-2 mRNA production in EL-4 T cells, and this repression is dependent on the ZEB-binding site at -100. ZEB1 cooperates with the co-repressor C-terminal-binding protein (CtBP) 2 and with histone deacetylase 1 to repress the IL-2 promoter and this cooperation depends on the ZEB-binding site in the promoter as well as the Pro-X-Asp-Leu-Ser protein-protein interaction domain in CtBP2. Thus, ZEB1 may function to recruit a repressor complex to the IL-2 promoter.

  16. Neonatal brainstem dysfunction risks infant social engagement

    PubMed Central

    Sopher, Koreen; Kurtzman, Lea; Galili, Giora; Feldman, Ruth; Kuint, Jacob

    2013-01-01

    The role of the brainstem in mediating social signaling in phylogenetic ancestral organisms has been demonstrated. Evidence for its involvement in social engagement in human infants may deepen the understanding of the evolutionary pathway of humans as social beings. In this longitudinal study, neonatal brainstem functioning was measured by auditory brainstem-evoked responses (ABRs) in 125 healthy neonates born prematurely before 35 weeks’ gestational age. At 4 months, infants were tested in a set of structured vignettes that required varying levels of social engagement and cardiac vagal tone was assessed. Data show that neonates with a disrupted I–V waveform, evident mostly by delayed wave V, exhibit shorter latencies to gaze averts in episodes involving direct face-to-face interactions but engage gaze as controls when interacting with masked agents or with agents whose faces are partly veiled by toys. Analysis of variance of infants’ social engagement with ABR, neonatal risk, maternal stress and cardiac vagal tone showed a main effect for ABR and an ABR by gestational age interaction. The integrity of brainstem transmission of sensory information during the final weeks of gestation may scaffold the development of social disengagement, thereby attesting to the brainstem's preserved evolutionary role in developing humans as social organisms prior to engaging in social encounters. PMID:22146141

  17. Killer whale (Orcinus orca) hearing: auditory brainstem response and behavioral audiograms.

    PubMed

    Szymanski, M D; Bain, D E; Kiehl, K; Pennington, S; Wong, S; Henry, K R

    1999-08-01

    Killer whale (Orcinus orca) audiograms were measured using behavioral responses and auditory evoked potentials (AEPs) from two trained adult females. The mean auditory brainstem response (ABR) audiogram to tones between 1 and 100 kHz was 12 dB (re 1 mu Pa) less sensitive than behavioral audiograms from the same individuals (+/- 8 dB). The ABR and behavioral audiogram curves had shapes that were generally consistent and had the best threshold agreement (5 dB) in the most sensitive range 18-42 kHz, and the least (22 dB) at higher frequencies 60-100 kHz. The most sensitive frequency in the mean Orcinus audiogram was 20 kHz (36 dB), a frequency lower than many other odontocetes, but one that matches peak spectral energy reported for wild killer whale echolocation clicks. A previously reported audiogram of a male Orcinus had greatest sensitivity in this range (15 kHz, approximately 35 dB). Both whales reliably responded to 100-kHz tones (95 dB), and one whale to a 120-kHz tone, a variation from an earlier reported high-frequency limit of 32 kHz for a male Orcinus. Despite smaller amplitude ABRs than smaller delphinids, the results demonstrated that ABR audiometry can provide a useful suprathreshold estimate of hearing range in toothed whales.

  18. The cis-regulatory element CCACGTGG is involved in ABA and water-stress responses of the maize gene rab28.

    PubMed

    Pla, M; Vilardell, J; Guiltinan, M J; Marcotte, W R; Niogret, M F; Quatrano, R S; Pagès, M

    1993-01-01

    The maize gene rab28 has been identified as ABA-inducible in embryos and vegetative tissues. It is also induced by water stress in young leaves. The proximal promoter region contains the conserved cis-acting element CCACGTGG (ABRE) reported for ABA induction in other plant genes. Transient expression assays in rice protoplasts indicate that a 134 bp fragment (-194 to -60 containing the ABRE) fused to a truncated cauliflower mosaic virus promoter (35S) is sufficient to confer ABA-responsiveness upon the GUS reporter gene. Gel retardation experiments indicate that nuclear proteins from tissues in which the rab28 gene is expressed can interact specifically with this 134 bp DNA fragment. Nuclear protein extracts from embryo and water-stressed leaves generate specific complexes of different electrophoretic mobility which are stable in the presence of detergent and high salt. However, by DMS footprinting the same guanine-specific contacts with the ABRE in both the embryo and leaf binding activities were detected. These results indicate that the rab28 promoter sequence CCACGTGG is a functional ABA-responsive element, and suggest that distinct regulatory factors with apparent similar affinity for the ABRE sequence may be involved in the hormone action during embryo development and in vegetative tissues subjected to osmotic stress.

  19. Public health evolutionary biology of antimicrobial resistance: priorities for intervention

    PubMed Central

    Baquero, Fernando; Lanza, Val F; Cantón, Rafael; Coque, Teresa M

    2015-01-01

    The three main processes shaping the evolutionary ecology of antibiotic resistance (AbR) involve the emergence, invasion and occupation by antibiotic-resistant genes of significant environments for human health. The process of emergence in complex bacterial populations is a high-frequency, continuous swarming of ephemeral combinatory genetic and epigenetic explorations inside cells and among cells, populations and communities, expanding in different environments (migration), creating the stochastic variation required for evolutionary progress. Invasion refers to the process by which AbR significantly increases in frequency in a given (invaded) environment, led by external invaders local multiplication and spread, or by endogenous conversion. Conversion occurs because of the spread of AbR genes from an exogenous resistant clone into an established (endogenous) bacterial clone(s) colonizing the environment; and/or because of dissemination of particular resistant genetic variants that emerged within an endogenous clonal population. Occupation of a given environment by a resistant variant means a permanent establishment of this organism in this environment, even in the absence of antibiotic selection. Specific interventions on emergence influence invasion, those acting on invasion also influence occupation and interventions on occupation determine emergence. Such interventions should be simultaneously applied, as they are not simple solutions to the complex problem of AbR. PMID:25861381

  20. Ear asymmetries in middle-ear, cochlear, and brainstem responses in human infants

    PubMed Central

    Keefe, Douglas H.; Gorga, Michael P.; Jesteadt, Walt; Smith, Lynette M.

    2008-01-01

    In 2004, Sininger and Cone-Wesson examined asymmetries in the signal-to-noise ratio (SNR) of otoacoustic emissions (OAE) in infants, reporting that distortion-product (DP)OAE SNR was larger in the left ear, whereas transient-evoked (TE)OAE SNR was larger in the right. They proposed that cochlear and brainstem asymmetries facilitate development of brain-hemispheric specialization for sound processing. Similarly, in 2006 Sininger and Cone-Wesson described ear asymmetries mainly favoring the right ear in infant auditory brainstem responses (ABRs). The present study analyzed 2640 infant responses to further explore these effects. Ear differences in OAE SNR, signal, and noise were evaluated separately and across frequencies (1.5, 2, 3, and 4 kHz), and ABR asymmetries were compared with cochlear asymmetries. Analyses of ear-canal reflectance and admittance showed that asymmetries in middle-ear functioning did not explain cochlear and brainstem asymmetries. Current results are consistent with earlier studies showing right-ear dominance for TEOAE and ABR. Noise levels were higher in the right ear for OAEs and ABRs, causing ear asymmetries in SNR to differ from those in signal level. No left-ear dominance for DPOAE signal was observed. These results do not support a theory that ear asymmetries in cochlear processing mimic hemispheric brain specialization for auditory processing. PMID:18345839

  1. Sugar for the brain: the role of glucose in physiological and pathological brain function

    PubMed Central

    Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A.; Meisel, Andreas

    2013-01-01

    The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We aim at synthesizing these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation which lead to disease. PMID:23968694

  2. Abscisic-acid-dependent basic leucine zipper (bZIP) transcription factors in plant abiotic stress.

    PubMed

    Banerjee, Aditya; Roychoudhury, Aryadeep

    2017-01-01

    One of the major causes of significant crop loss throughout the world is the myriad of environmental stresses including drought, salinity, cold, heavy metal toxicity, and ultraviolet-B (UV-B) rays. Plants as sessile organisms have evolved various effective mechanism which enable them to withstand this plethora of stresses. Most of such regulatory mechanisms usually follow the abscisic-acid (ABA)-dependent pathway. In this review, we have primarily focussed on the basic leucine zipper (bZIP) transcription factors (TFs) activated by the ABA-mediated signalosome. Upon perception of ABA by specialized receptors, the signal is transduced via various groups of Ser/Thr kinases, which phosphorylate the bZIP TFs. Following such post-translational modification of TFs, they are activated so that they bind to specific cis-acting sequences called abscisic-acid-responsive elements (ABREs) or GC-rich coupling elements (CE), thereby influencing the expression of their target downstream genes. Several in silico techniques have been adopted so far to predict the structural features, recognize the regulatory modification sites, undergo phylogenetic analyses, and facilitate genome-wide survey of TF under multiple stresses. Current investigations on the epigenetic regulation that controls greater accessibility of the inducible regions of DNA of the target gene to the bZIP TFs exclusively under stress situations, along with the evolved stress memory responses via genomic imprinting mechanism, have been highlighted. The potentiality of overexpression of bZIP TFs, either in a homologous or in a heterologous background, in generating transgenic plants tolerant to various abiotic stressors have also been addressed by various groups. The present review will provide a coherent documentation on the functional characterization and regulation of bZIP TFs under multiple environmental stresses, with the major goal of generating multiple-stress-tolerant plant cultivars in near future.

  3. Widespread evidence of cooperative DNA binding by transcription factors in Drosophila development

    PubMed Central

    Kazemian, Majid; Pham, Hannah; Wolfe, Scot A.; Brodsky, Michael H.; Sinha, Saurabh

    2013-01-01

    Regulation of eukaryotic gene transcription is often combinatorial in nature, with multiple transcription factors (TFs) regulating common target genes, often through direct or indirect mutual interactions. Many individual examples of cooperative binding by directly interacting TFs have been identified, but it remains unclear how pervasive this mechanism is during animal development. Cooperative TF binding should be manifest in genomic sequences as biased arrangements of TF-binding sites. Here, we explore the extent and diversity of such arrangements related to gene regulation during Drosophila embryogenesis. We used the DNA-binding specificities of 322 TFs along with chromatin accessibility information to identify enriched spacing and orientation patterns of TF-binding site pairs. We developed a new statistical approach for this task, specifically designed to accurately assess inter-site spacing biases while accounting for the phenomenon of homotypic site clustering commonly observed in developmental regulatory regions. We observed a large number of short-range distance preferences between TF-binding site pairs, including examples where the preference depends on the relative orientation of the binding sites. To test whether these binding site patterns reflect physical interactions between the corresponding TFs, we analyzed 27 TF pairs whose binding sites exhibited short distance preferences. In vitro protein–protein binding experiments revealed that >65% of these TF pairs can directly interact with each other. For five pairs, we further demonstrate that they bind cooperatively to DNA if both sites are present with the preferred spacing. This study demonstrates how DNA-binding motifs can be used to produce a comprehensive map of sequence signatures for different mechanisms of combinatorial TF action. PMID:23847101

  4. Widespread evidence of cooperative DNA binding by transcription factors in Drosophila development.

    PubMed

    Kazemian, Majid; Pham, Hannah; Wolfe, Scot A; Brodsky, Michael H; Sinha, Saurabh

    2013-09-01

    Regulation of eukaryotic gene transcription is often combinatorial in nature, with multiple transcription factors (TFs) regulating common target genes, often through direct or indirect mutual interactions. Many individual examples of cooperative binding by directly interacting TFs have been identified, but it remains unclear how pervasive this mechanism is during animal development. Cooperative TF binding should be manifest in genomic sequences as biased arrangements of TF-binding sites. Here, we explore the extent and diversity of such arrangements related to gene regulation during Drosophila embryogenesis. We used the DNA-binding specificities of 322 TFs along with chromatin accessibility information to identify enriched spacing and orientation patterns of TF-binding site pairs. We developed a new statistical approach for this task, specifically designed to accurately assess inter-site spacing biases while accounting for the phenomenon of homotypic site clustering commonly observed in developmental regulatory regions. We observed a large number of short-range distance preferences between TF-binding site pairs, including examples where the preference depends on the relative orientation of the binding sites. To test whether these binding site patterns reflect physical interactions between the corresponding TFs, we analyzed 27 TF pairs whose binding sites exhibited short distance preferences. In vitro protein-protein binding experiments revealed that >65% of these TF pairs can directly interact with each other. For five pairs, we further demonstrate that they bind cooperatively to DNA if both sites are present with the preferred spacing. This study demonstrates how DNA-binding motifs can be used to produce a comprehensive map of sequence signatures for different mechanisms of combinatorial TF action.

  5. Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes

    PubMed Central

    Schreiner, Sabrina; Bürck, Carolin; Glass, Mandy; Groitl, Peter; Wimmer, Peter; Kinkley, Sarah; Mund, Andreas; Everett, Roger D.; Dobner, Thomas

    2013-01-01

    Death domain–associated protein (Daxx) cooperates with X-linked α-thalassaemia retardation syndrome protein (ATRX), a putative member of the sucrose non-fermentable 2 family of ATP-dependent chromatin-remodelling proteins, acting as the core ATPase subunit in this complex, whereas Daxx is the targeting factor, leading to histone deacetylase recruitment, H3.3 deposition and transcriptional repression of cellular promoters. Despite recent findings on the fundamental importance of chromatin modification in host-cell gene regulation, it remains unclear whether adenovirus type 5 (Ad5) transcription is regulated by cellular chromatin remodelling to allow efficient virus gene expression. Here, we focus on the repressive role of the Daxx/ATRX complex during Ad5 replication, which depends on intact protein–protein interaction, as negative regulation could be relieved with a Daxx mutant that is unable to interact with ATRX. To ensure efficient viral replication, Ad5 E1B-55K protein inhibits Daxx and targets ATRX for proteasomal degradation in cooperation with early region 4 open reading frame protein 6 and cellular components of a cullin-dependent E3-ubiquitin ligase. Our studies illustrate the importance and diversity of viral factors antagonizing Daxx/ATRX-mediated repression of viral gene expression and shed new light on the modulation of cellular chromatin remodelling factors by Ad5. We show for the first time that cellular Daxx/ATRX chromatin remodelling complexes play essential roles in Ad gene expression and illustrate the importance of early viral proteins to counteract cellular chromatin remodelling. PMID:23396441

  6. 78 FR 28492 - Special Local Regulation; Low Country Splash, Wando River, Cooper River, and Charleston Harbor...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-15

    ... to the local maritime community via broadcast notice to mariners. 2. Impact on Small Entities Under...-AA08 Special Local Regulation; Low Country Splash, Wando River, Cooper River, and Charleston Harbor... establishing a special local regulation on the waters of the Wando River, Cooper River, and Charleston Harbor...

  7. 33 CFR 100.T07-0110 - Special Local Regulations; Low Country Splash, Wando River, Cooper River, and Charleston Harbor...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Special Local Regulations; Low Country Splash, Wando River, Cooper River, and Charleston Harbor, Charleston, SC. 100.T07-0110 Section 100... Splash, Wando River, Cooper River, and Charleston Harbor, Charleston, SC. (a) Regulated Areas. The...

  8. Regulation during Cooperative and Collaborative Learning: A Theory-Based Review of Terms and Concepts

    ERIC Educational Resources Information Center

    Schoor, Cornelia; Narciss, Susanne; Körndle, Hermann

    2015-01-01

    This article reviews the terms and concepts that have been used for describing regulation of learning during cooperative and collaborative learning and suggests differentiating them on the basis of which parts of a regulatory feedback loop model are being shared. During cooperative and collaborative learning, not only self-regulation but also the…

  9. Variable responses of two VlMYBA gene promoters to ABA and ACC in Kyoho grape berries.

    PubMed

    Zhai, Xiawan; Zhang, Yushu; Kai, Wenbin; Liang, Bin; Jiang, Li; Du, Yangwei; Wang, Juan; Sun, Yufei; Leng, Ping

    2017-04-01

    The VlMYBA subfamily of transcription factors has been known to be the functional regulators in anthocyanin biosynthesis in red grapes. In this study, the expressions of the VlMYBA1-2 and VlMYBA 2 genes, and the responses of the VlMYBA1-2/2 promoters to ABA and ACC treatments in Kyoho grape berries are examined through quantitative real-time PCR analysis and the transient expression assay. The results show that the expressions of VlMYBA1-2/2 increase dramatically after véraison and reach their highest levels when the berries are nearly fully ripe. Exogenous ABA promotes the expressions of VlMYBA1-2/2, whereas the ACC treatment increases the expression of VlMYBA2, however, it has no effect on VlMYBA1-2. The ABA treatment has a faster and stronger effect on berry pigmentation than ACC does. The VlMYBA1-2 promoter sequence contains two ABA response elements (ABRE) but no ethylene response element (ERE), whereas the VlMYBA2 promoter sequence contains two ABRE and one ERE in the upstream region of the start codon. The VlMYBA2 promoter can be activated by both ABA (more effective) and ACC, whereas the VlMYBA1-2 promoter can be activated by ABA only. In sum, ABA can promote the coloring of Kyoho grape by the promotion of VlMYBA1-2/2 transcriptions via activating the response of their promoters to ABA, whereas ethylene only regulates VlMYBA2 through the response activation of its promoter to ACC which partially enhances the coloring. Copyright © 2017 Elsevier GmbH. All rights reserved.

  10. Computational prediction and experimental verification of HVA1-like abscisic acid responsive promoters in rice (Oryza sativa).

    PubMed

    Ross, Christian; Shen, Qingxi J

    2006-09-01

    Abscisic acid (ABA) is one of the central plant hormones, responsible for controlling both maturation and germination in seeds, as well as mediating adaptive responses to desiccation, injury, and pathogen infection in vegetative tissues. Thorough analyses of two barley genes, HVA1 and HVA22, indicate that their response to ABA relies on the interaction of two cis-acting elements in their promoters, an ABA response element (ABRE) and a coupling element (CE). Together, they form an ABA response promoter complex (ABRC). Comparison of promoters of barley HVA1 and it rice orthologue indicates that the structures and sequences of their ABRCs are highly similar. Prediction of ABA responsive genes in the rice genome is then tractable to a bioinformatics approach based on the structures of the well-defined barley ABRCs. Here we describe a model developed based on the consensus, inter-element spacing and orientations of experimentally determined ABREs and CEs. Our search of the rice promoter database for promoters that fit the model has generated a partial list of genes in rice that have a high likelihood of being involved in the ABA signaling network. The ABA inducibility of some of the rice genes identified was validated with quantitative reverse transcription PCR (QPCR). By limiting our input data to known enhancer modules and experimentally derived rules, we have generated a high confidence subset of ABA-regulated genes. The results suggest that the pathways by which cereals respond to biotic and abiotic stresses overlap significantly, and that regulation is not confined to the level transcription. The large fraction of putative regulatory genes carrying HVA1-like enhancer modules in their promoters suggests the ABA signal enters at multiple points into a complex regulatory network that remains largely unmapped.

  11. [Effects of electrical stimulation at acupoints in the distribution area of auricular vagus nerve combined with sound masking method on auditory brainstem response and neurotransmitters of inferior colliculus in rats of tinnitus].

    PubMed

    Yang, Songbai; Mei, Zhigang; Tan, Lingjing; Ma, Wenhan; Zhang, Dingqi; Wang, Zhaojun; Li, Tiantian; Huang, Kunyan; Cai, Sanjin

    2016-05-01

    To explore the effects of electrical stimulation at acupoints in the distribution area of auricular vagus nerve combined with sound masking on auditory brainstem response (ABR) and contents of neurotransmitters of γ-aminobutyric acid (γ-GABA), 5-hydroxytryptamine (5-HT) and acetyl choline (Ach) in inferior colliculus of tinnitus rats. Twenty-four male adult SD rats were randomized into a control group, a model group, a 7-d treatment group and a 15-d treatment group. Except the control group, rats in the remaining groups were treated with intraperitoneal injection of 10% salicylate sodium at a dose of 350 mg/kg to establish tinnitus model. Rats in the control group were treated with injection of 0.9% NaCl. Rats in the 7-d treatment group and 15-d treatment group were treated with electrical stimulation at "Shenmen (TF₄)" and "Yidan (CO₁₁)" in the distribution area of auricular vagus nerve combined with sound masking, once a day, for 7 days and 15 days. The SigGenRP software of TDT system was applied to provide voice for single ear and collect the signal, and the voice threshold of ABR was tested. The levels of γ-GABA, 5-HT and Ach in inferior colliculus of rats were detected by enzyme linked immunosorbent assay (ELISA) and compared. Compared with the model group, the threshold values of ABR in 12 kHz and 16 kHz voice stimulation in the 7-d treatment group were significantly lower all P < 0.05); the threshold values of ABR from 4 kHz to 28 kHz voice stimulation in the 15-d treatment group were signally reduced (P < 0.05, P < 0.01), which was more significant than those in the 7-d treatment group. The level of γ-GABA in the model group was significantly lower than that in the control group (P < 0.05), and that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of 5-HT in the model group was markedly higher than that in the control group (P < 0.05), and that in the 7-d treatment group was lower than that in the model group (P < 0.05), while that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of Ach in the model group was obviously; lower than that in the control group (P < 0.05), and that in the 7-d treatment group was higher than that in the model group (P < 0.05). Electrical stimulation at auricular vagus nerve combined with sound masking) could regulate the threshold of ABR, especially in the 15-d treatment group. This may be ascribed to modulating the levels of neurotransmitter of γ-GABA, 5-HT and Ach in inferior colliculus.

  12. [Optimization of Energy Saving Measures with ABR-MBR Integrated Process].

    PubMed

    Wu, Peng; Lu, Shuang-jun; Xu, Yue-zhong; Liu, Jie; Shen, Yao-liang

    2015-08-01

    High energy consumption and membrane fouling are important factors that limit the wide use of membrane bioreactor (MBR). In order to reduce energy consumption and delay the process of membrane fouling, the process of anaerobic baffled reactor (ABR)-MBR was used to treat domestic sewage. The structure of the process and conditions of nitrogen and phosphorus removal were optimized in this study. The results showed that energy consumption was reduced by 43% through optimizing the structure of ABR-MBR process. Meanwhile, the process achieved a high level of COD, NH: -N, TN and TP removal, with the average removal efficiencies of 91%, 85%, 76% and 86%, respectively. In addition, the added particulate media could effectively delay membrane fouling, while the formation process of membrane fouling was changed. The extracted amount of carbohydrates increased while the amount of proteins decreased. Finally, the potential was enhanced for the practical application of MBR.

  13. High-frequency toneburst-evoked ABR latency-intensity functions in sensorineural hearing-impaired humans.

    PubMed

    Fausti, S A; Olson, D J; Frey, R H; Henry, J A; Schaffer, H I; Phillips, D S

    1995-01-01

    The latency-intensity functions (LIFs) of ABRs elicited by high-frequency (8, 10, 12, and 14 kHz) toneburst stimuli were evaluated in 20 subjects with confirmed 'moderate' high-frequency sensorineural hearing loss. Wave V results from clicks and tonebursts revealed all intra- and intersession data to be reliable (p > 0.05). Linear regression curves were highly significant (p < or = 0.0001), indicating linear relationships for all stimuli analyzed. Comparisons between the linear regression curves from a previously reported normal-hearing subject group and this sensorineural hearing-impaired group showed no significant differences. This study demonstrated that tonebursts at 8, 10, and 12 kHz evoked ABRs which decreased in latency as a function of increasing intensity and that these LIFs were consistent and orderly (14 kHz was not determinable). These results will contribute information to facilitate the establishment of change criteria used to predict change in hearing during treatment with ototoxic medications.

  14. Large-scale Phenotyping of Noise-Induced Hearing Loss in 100 Strains of Mice

    PubMed Central

    Myint, Anthony; White, Cory H.; Ohmen, Jeffrey D.; Li, Xin; Wang, Juemei; Lavinsky, Joel; Salehi, Pezhman; Crow, Amanda L.; Ohyama, Takahiro; Friedman, Rick A.

    2015-01-01

    A cornerstone technique in the study of hearing is the Auditory Brainstem Response (ABR), an electrophysiologic technique that can be used as a quantitative measure of hearing function. Previous studies have published databases of baseline ABR thresholds for mouse strains, providing a valuable resource for the study of baseline hearing function and genetic mapping of hearing traits in mice. In this study, we further expand upon the existing literature by characterizing the baseline ABR characteristics of 100 inbred mouse strains, 47 of which are newly characterized for hearing function. We identify several distinct patterns of baseline hearing deficits and provide potential avenues for further investigation. Additionally, we characterize the sensitivity of the same 100 strains to noise exposure using permanent thresholds shifts, identifying several distinct patterns of noise-sensitivity. The resulting data provides a new resource for studying hearing loss and noise-sensitivity in mice. PMID:26706709

  15. Forecasting the Effect of the Change in Timing of the ABR Diagnostic Radiology Examinations: Results of the ACR Survey of Practice Leaders.

    PubMed

    Bluth, Edward I; Muroff, Lawrence R; Cernigliaro, Joseph G; Moore, Arl V; Smith, Geoffrey G; Flug, Jonathan; DeStigter, Kristen K; Allen, Bibb; Thorwarth, William T; Roberts, Anne C

    2015-05-01

    The results of a survey sent to practice leaders in the ACR Practice of Radiology Environment Database show that the majority of responding groups will continue to hire recently trained residents and fellows even though they have been unable to take the final ABR diagnostic radiology certifying examination. However, a significant minority of private practice groups will not hire these individuals. The majority of private practices expect the timing change for the ABR certifying examinations to affect their groups' function. In contrast, the majority of academic medical school practices expect little or no impact. Residents and fellows should not expect work time off or protected time to study for the certifying examination or for their maintenance of certification examinations in the future. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  16. A proposed medical physics curriculum: preparing for the 2013 ABR examination.

    PubMed

    Nachiappan, Arun C; Wynne, David M; Katz, David P; Willis, Marc H; Bushong, Stewart C

    2011-01-01

    The upcoming ABR examination format for radiology residents is undergoing significant changes in 2013. This requires adaptation of the didactic curriculum for radiology residents entering in July 2010 to meet these changes. Physics will now be incorporated into the core (qualifying) examination during the third year of residency, instead of being tested as a separate examination that was often taken earlier in residency training in past years. In this article, the authors discuss the past, present, and future of medical physics instruction and outline a revised medical physics curriculum for radiology residents that has been internally approved for implementation at the authors' institution and has not been advocated by any society or by the ABR. Starting with this article, the authors hope to encourage a discussion of physics curriculum revision with other institutions. Copyright © 2011 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  17. Effect of Hand Antisepsis Agent Selection and Population Characteristics on Surgical Site Infection Pathogens.

    PubMed

    Oriel, Brad S; Chen, Qi; Wong, Kevin; Itani, Kamal M F

    Selection of a pre-operative hand antisepsis agent has not been studied in relation to surgical site infection (SSI) culture data. In our hospital, we introduced an alcohol-based hand rub (ABR) in 2012 as an alternative to traditional aqueous surgical scrubs (TSS). It was the goal of this study to review any effect of this implementation on SSI pathogen characteristics. In addition, we sought to compare our SSI culture data with available National Healthcare Safety Network (NHSN) data. We hypothesized that SSI pathogens and resistant isolates are affected by surgical hand antisepsis technique. Data collected prospectively between 2007 and 2014 were retrospectively analyzed for two time periods at the Veterans Affairs Boston Healthcare System (VABHS): Before ABR implementation (TSS group) and after (ABR group). Pathogen distribution and pathogenic isolate resistance profiles were compared for TSS and ABR, and similar comparisons, along with procedure-associated SSI comparisons, were made between VABHS and NHSN. All VABHS data were interpreted and categorized according to NHSN definitions. Compared with TSS (n = 4,051), ABR (n = 2,293) had a greater rate of Staphylococcus aureus (42.6% vs. 38.0%), Escherichia coli (12.8% vs. 9.9%), Pseudomonas aeruginosa (8.5% vs. 2.8%), and Enterobacter spp. (10.6% vs. 2.8%), and a lower rate of Klebsiella pneumoniae/K. oxytoca (4.3% vs. 8.5%) cultured from superficial and deep SSIs (p < 0.05). Of the S. aureus isolates, 35.0% and 44.4% were resistant to oxacillin/methicillin (MRSA) in ABR and TSS, respectively (p = 0.06). Looking at all SSIs, coagulase-negative staphylococci and K. pneumoniae/K. oxytoca at VABHS (4.0% and 10.4%, respectively) accounted for the biggest difference from NHSN (11.7% and 4.0%, respectively). Aside from MRSA, where there was no difference between VABHS and NHSN (42.9% vs. 43.7%, respectively; p = 0.87), statistically significant (p < 0.05) differences were observed among multi-drug-resistant K. pneumoniae/K. oxytoca (0% vs. 6.8%, respectively) and Escherichia coli (10.0% vs. 1.6%, respectively), as well as among extended-spectrum cephalosporin-resistant K. pneumoniae/K. oxytoca (4.8% vs. 13.2%, respectively) and Enterobacter (58.3% vs. 27.7%, respectively). VABHS had a greater proportion of SSIs in abdominal and vascular cases than did NHSN (48.6% vs. 22.5% and 13.2% vs. 1.5%, respectively). Overall, these differences were significant (p < 0.05). The TSS and ABR groups differed in the distribution of pathogens recovered. Those differences, along with SSI pathogen distribution, pathogenic isolate resistance profiles, and procedure-associated SSIs between VABHS and NHSN, warrant further investigation.

  18. Shikonin regulates C-MYC and GLUT1 expression through the MST1-YAP1-TEAD1 axis

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

    Vališ, Karel, E-mail: karel.valis@biomed.cas.cz; Faculty of Science, Charles University, Prague; Talacko, Pavel

    The general mechanism underlying the tumor suppressor activity of the Hippo signaling pathway remains unclear. In this study, we explore the molecular mechanisms connecting the Hippo signaling pathway with glucose metabolism. We have found that two key regulators of glycolysis, C-MYC and GLUT1, are targets of the Hippo signaling pathway in human leukemia cells. Our results revealed that activation of MST1 by the natural compound shikonin inhibited the expression of GLUT1 and C-MYC. Furthermore, RNAi experiments confirmed the regulation of GLUT1 and C-MYC expression via the MST1-YAP1-TEAD1 axis. Surprisingly, YAP1 was found to positively regulate C-MYC mRNA levels in complexmore » with TEAD1, while it negatively regulates C-MYC levels in cooperation with MST1. Hence, YAP1 serves as a rheostat for C-MYC, which is regulated by MST1. In addition, depletion of MST1 stimulates lactate production, whereas the specific depletion of TEAD1 has an opposite effect. The inhibition of lactate production and cellular proliferation induced by shikonin also depends on the Hippo pathway activity. Finally, a bioinformatic analysis revealed conserved TEAD-binding motifs in the C-MYC and GLUT1 promoters providing another molecular data supporting our observations. In summary, regulation of glucose metabolism could serve as a new tumor suppressor mechanism orchestrated by the Hippo signaling pathway. - Highlights: • Shikonin inhibits C-MYC and GLUT1 expression in MST1 and YAP1 dependent manner. • YAP1-TEAD1 interaction activates C-MYC and GLUT1 expression. • MST1 in cooperation with YAP1 inhibits C-MYC and GLUT1 expression. • MST1-YAP1-TEAD1 axis regulates lactate production by leukemic cells. • MST1 and YAP1 proteins block proliferation of leukemic cells.« less

  19. 7 CFR 1124.18 - Cooperative association.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Cooperative association. 1124.18 Section 1124.18 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Regulating Handling Definitions § 1124.18 Cooperative association. See § 1000.18. ...

  20. 7 CFR 1030.18 - Cooperative association.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Cooperative association. 1030.18 Section 1030.18 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Regulating Handling Definitions § 1030.18 Cooperative association. See § 1000.18. ...

  1. 7 CFR 1005.18 - Cooperative association.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Cooperative association. 1005.18 Section 1005.18 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Regulating Handling Definitions § 1005.18 Cooperative association. See § 1000.18. ...

  2. Mediator complex cooperatively regulates transcription of retinoic acid target genes with Polycomb Repressive Complex 2 during neuronal differentiation.

    PubMed

    Fukasawa, Rikiya; Iida, Satoshi; Tsutsui, Taiki; Hirose, Yutaka; Ohkuma, Yoshiaki

    2015-11-01

    The Mediator complex (Mediator) plays key roles in transcription and functions as the nexus for integration of various transcriptional signals. Previously, we screened for Mediator cyclin-dependent kinase (CDK)-interacting factors and identified three proteins related to chromatin regulation. One of them, SUZ12 is required for both stability and activity of Polycomb Repressive Complex 2 (PRC2). PRC2 primarily suppresses gene expression through histone H3 lysine 27 trimethylation, resulting in stem cell maintenance and differentiation; perturbation of this process leads to oncogenesis. Recent work showed that Mediator contributes to the embryonic stem cell state through DNA loop formation, which is strongly associated with chromatin architecture; however, it remains unclear how Mediator regulates gene expression in cooperation with chromatin regulators (i.e. writers, readers and remodelers). We found that Mediator CDKs interact directly with the PRC2 subunit EZH2, as well as SUZ12. Known PRC2 target genes were deregulated by Mediator CDK knockdown during neuronal differentiation, and both Mediator and PRC2 complexes co-occupied the promoters of developmental genes regulated by retinoic acid. Our results provide a mechanistic link between Mediator and PRC2 during neuronal differentiation. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  3. Interplay between TGF-β signaling and receptor tyrosine kinases in tumor development.

    PubMed

    Shi, Qiaoni; Chen, Ye-Guang

    2017-10-01

    Transforming growth factor-β (TGF-β) signaling regulates cell proliferation, differentiation, migration and death, and plays a critical role in embryogenesis and tissue homeostasis. Its deregulation results in various diseases including tumor formation. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR), also play key roles in the development and progression of many types of tumors. It has been realized that TGF-β signaling and RTK pathways interact with each other and their interplay is important for cancer development. They are mutually regulated and cooperatively modulate cell survival and migration, epithelial-mesenchymal transition, and tumor microenvironment to accelerate tumorigenesis and tumor metastasis. RTKs can modulate Smad-dependent transcription or cooperate with TGF-β to potentiate its oncogenic activity, while TGF-β signaling can in turn control RTK signaling by regulating their activities or expression. This review summarizes current understandings of the interplay between TGF-β signaling and RTKs and its influence on tumor development.

  4. Gap prepulse inhibition and auditory brainstem-evoked potentials as objective measures for tinnitus in guinea pigs

    PubMed Central

    Dehmel, Susanne; Eisinger, Daniel; Shore, Susan E.

    2012-01-01

    Tinnitus or ringing of the ears is a subjective phantom sensation necessitating behavioral models that objectively demonstrate the existence and quality of the tinnitus sensation. The gap detection test uses the acoustic startle response elicited by loud noise pulses and its gating or suppression by preceding sub-startling prepulses. Gaps in noise bands serve as prepulses, assuming that ongoing tinnitus masks the gap and results in impaired gap detection. This test has shown its reliability in rats, mice, and gerbils. No data exists for the guinea pig so far, although gap detection is similar across mammals and the acoustic startle response is a well-established tool in guinea pig studies of psychiatric disorders and in pharmacological studies. Here we investigated the startle behavior and prepulse inhibition (PPI) of the guinea pig and showed that guinea pigs have a reliable startle response that can be suppressed by 15 ms gaps embedded in narrow noise bands preceding the startle noise pulse. After recovery of auditory brainstem response (ABR) thresholds from a unilateral noise over-exposure centered at 7 kHz, guinea pigs showed diminished gap-induced reduction of the startle response in frequency bands between 8 and 18 kHz. This suggests the development of tinnitus in frequency regions that showed a temporary threshold shift (TTS) after noise over-exposure. Changes in discharge rate and synchrony, two neuronal correlates of tinnitus, should be reflected in altered ABR waveforms, which would be useful to objectively detect tinnitus and its localization to auditory brainstem structures. Therefore, we analyzed latencies and amplitudes of the first five ABR waves at suprathreshold sound intensities and correlated ABR abnormalities with the results of the behavioral tinnitus testing. Early ABR wave amplitudes up to N3 were increased for animals with tinnitus possibly stemming from hyperactivity and hypersynchrony underlying the tinnitus percept. Animals that did not develop tinnitus after noise exposure showed the opposite effect, a decrease in wave amplitudes for the later waves P4–P5. Changes in latencies were only observed in tinnitus animals, which showed increased latencies. Thus, tinnitus-induced changes in the discharge activity of the auditory nerve and central auditory nuclei are represented in the ABR. PMID:22666193

  5. 7 CFR 4285.81 - Cooperative agreement awards.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE COOPERATIVE AGREEMENTS Federal-State Research on... the methods identified in approved application and budget, the regulations of this part, the terms and...

  6. [Impact of hypoglycemic episodes on nerves conduction and auditory and visual evoked potentials in children with type 1 diabetes].

    PubMed

    Wysocka-Mincewicz, Marta; Trippenbach-Dulska, Hanna; Emeryk-Szajewska, Barbara; Zakrzewska-Pniewska, Beata; Kochanek, Krzysztof; Pańkowska, Ewa

    2007-01-01

    Hypoglycemia is an acute disturbance of energy, especially impacting the central nervous system, but direct influence on peripheral nervous function is not detected. The aim of the study was to establish the influence of hypoglycemic moderate and severe episodes on the function of peripheral nerves, hearing and visual pathway. 97 children with type 1 diabetes (mean age 15.4+/-2.16 years, mean duration of diabetes 8.11+/-2.9 years, mean HbA1c 8,58+/-1.06%), at least 10 years old and with at least 3 years duration of diabetes, were included to study. Nerve conduction studies, visual (VEP) and auditory (ABR) evoked potentials were performed with standard surface stimulating and recording techniques. Moderate hypoglycemic episodes were defined as events of low glycemia requiring help of another person but without loss of consciousness and/or convulsions but recurrent frequently in at least one year. Severe hypoglycemia was defined as events with loss of consciousness and/or convulsions. Univariate ANOVA tests of significance or H Kruskal-Wallis test were used, depending on normality of distribution. The subgroups with a history of hypoglycemic episodes had significant delay in all conduction parameters in the sural nerve (amplitude p<0.05, sensory latency p<0.05, and velocity p<0.005) and in motor potential amplitude of tibial nerve (p<0.005). In ABR wave III latency and interval I-III in subgroups with episodes of hypoglycemia (p<0,05) were significantly prolonged. In analyses of VEP parameters no differences were detected. The study showed influence of hypoglycemic episodes on function of all sural nerve parameters and tibial motor amplitude, and in ABR on wave III and interval I-III. Frequent moderate hypoglycemic episodes were strong risk factors for damage of the peripheral and central nervous systems, comparable with impact of several severe hypoglycemias.

  7. Loss of the Drosophila cell polarity regulator Scribbled promotes epithelial tissue overgrowth and cooperation with oncogenic Ras-Raf through impaired Hippo pathway signaling

    PubMed Central

    2011-01-01

    Background Epithelial neoplasias are associated with alterations in cell polarity and excessive cell proliferation, yet how these neoplastic properties are related to one another is still poorly understood. The study of Drosophila genes that function as neoplastic tumor suppressors by regulating both of these properties has significant potential to clarify this relationship. Results Here we show in Drosophila that loss of Scribbled (Scrib), a cell polarity regulator and neoplastic tumor suppressor, results in impaired Hippo pathway signaling in the epithelial tissues of both the eye and wing imaginal disc. scrib mutant tissue overgrowth, but not the loss of cell polarity, is dependent upon defective Hippo signaling and can be rescued by knockdown of either the TEAD/TEF family transcription factor Scalloped or the transcriptional coactivator Yorkie in the eye disc, or reducing levels of Yorkie in the wing disc. Furthermore, loss of Scrib sensitizes tissue to transformation by oncogenic Ras-Raf signaling, and Yorkie-Scalloped activity is required to promote this cooperative tumor overgrowth. The inhibition of Hippo signaling in scrib mutant eye disc clones is not dependent upon JNK activity, but can be significantly rescued by reducing aPKC kinase activity, and ectopic aPKC activity is sufficient to impair Hippo signaling in the eye disc, even when JNK signaling is blocked. In contrast, warts mutant overgrowth does not require aPKC activity. Moreover, reducing endogenous levels of aPKC or increasing Scrib or Lethal giant larvae levels does not promote increased Hippo signaling, suggesting that aPKC activity is not normally rate limiting for Hippo pathway activity. Epistasis experiments suggest that Hippo pathway inhibition in scrib mutants occurs, at least in part, downstream or in parallel to both the Expanded and Fat arms of Hippo pathway regulation. Conclusions Loss of Scrib promotes Yorkie/Scalloped-dependent epithelial tissue overgrowth, and this is also important for driving cooperative tumor overgrowth with oncogenic Ras-Raf signaling. Whether this is also the case in human cancers now warrants investigation since the cell polarity function of Scrib and its capacity to restrain oncogene-mediated transformation, as well as the tissue growth control function of the Hippo pathway, are conserved in mammals. PMID:21955824

  8. Plasticity of peripheral auditory frequency sensitivity in Emei music frog.

    PubMed

    Zhang, Dian; Cui, Jianguo; Tang, Yezhong

    2012-01-01

    In anurans reproductive behavior is strongly seasonal. During the spring, frogs emerge from hibernation and males vocalize for mating or advertising territories. Female frogs have the ability to evaluate the quality of the males' resources on the basis of these vocalizations. Although studies revealed that central single torus semicircularis neurons in frogs exhibit season plasticity, the plasticity of peripheral auditory sensitivity in frog is unknown. In this study the seasonally plasticity of peripheral auditory sensitivity was test in the Emei music frog Babina daunchina, by comparing thresholds and latencies of auditory brainstem responses (ABRs) evoked by tone pips and clicks in the reproductive and non-reproductive seasons. The results show that both ABR thresholds and latency differ significantly between the reproductive and non-reproductive seasons. The thresholds of tone pip evoked ABRs in the non-reproductive season increased significantly about 10 dB than those in the reproductive season for frequencies from 1 KHz to 6 KHz. ABR latencies to waveform valley values for tone pips for the same frequencies using appropriate threshold stimulus levels are longer than those in the reproductive season for frequencies from 1.5 to 6 KHz range, although from 0.2 to 1.5 KHz range it is shorter in the non-reproductive season. These results demonstrated that peripheral auditory frequency sensitivity exhibits seasonal plasticity changes which may be adaptive to seasonal reproductive behavior in frogs.

  9. Effects of the acute exposure to the electromagnetic field of mobile phones on human auditory brainstem responses.

    PubMed

    Oysu, Cagatay; Topak, Murat; Celik, Oner; Yilmaz, H Baki; Sahin, A Asli

    2005-10-01

    The purpose of this study was to evaluate the short-term effects of the electromagnetic fields (EMF) of mobile phones on human auditory brainstem responses. This prospective study of healthy adults evaluated the influence of EMF. Eighteen healthy adult volunteers participated in this study. Mobile telephones emitting signals in the region of 900 MHz and with the highest SAR value of 0.82 W/kg were positioned in direct contact to the right ear, which was exposed to the phone signal for 15 min before and after ABR testing with click stimuli of 60 and 80 dB nHL intensities. The latencies of the waves and interwave latencies were measured on screen by an experienced audiologist. The differences of the mean latencies of waves I, III and IV were not significant in initial and post-exposure ABR measurements at both 60 and 80 dB nHL stimulus levels ( P >0.05). Similarly, differences of the mean interwave intervals I-III, I-V and III-V remained insignificant at the initial and postexposure ABR measurements at stimulus levels of both 60 and 80 dB nHL ( P >0.05). Acute exposure to the EMF of mobile phones does not cause perturbations in ABR latencies. However, these negative results should not encourage excessive mobile communication, because minor biological and neurophysiological influences may not be detectable by the current technology.

  10. New insights into differential baroreflex control of heart rate in humans

    NASA Technical Reports Server (NTRS)

    Fadel, P. J.; Stromstad, M.; Wray, D. W.; Smith, S. A.; Raven, P. B.; Secher, N. H.

    2003-01-01

    Recent data indicate that bilateral carotid sinus denervation in patients results in a chronic impairment in the rapid reflex control of blood pressure during orthostasis. These findings are inconsistent with previous human experimental investigations indicating a minimal role for the carotid baroreceptor-cardiac reflex in blood pressure control. Therefore, we reexamined arterial baroreflex [carotid (CBR) and aortic baroreflex (ABR)] control of heart rate (HR) using newly developed methodologies. In 10 healthy men, 27 +/- 1 yr old, an abrupt decrease in mean arterial pressure (MAP) was induced nonpharmacologically by releasing a unilateral arterial thigh cuff (300 Torr) after 9 min of resting leg ischemia under two conditions: 1) ABR and CBR deactivation (control) and 2) ABR deactivation. Under control conditions, cuff release decreased MAP by 13 +/- 1 mmHg, whereas HR increased 11 +/- 2 beats/min. During ABR deactivation, neck suction was gradually applied to maintain carotid sinus transmural pressure during the initial 20 s after cuff release (suction). This attenuated the increase in HR (6 +/- 1 beats/min) and caused a greater decrease in MAP (18 +/- 2 mmHg, P < 0.05). Furthermore, estimated cardiac baroreflex responsiveness (DeltaHR/DeltaMAP) was significantly reduced during suction compared with control conditions. These findings suggest that the carotid baroreceptors contribute more importantly to the reflex control of HR than previously reported in healthy individuals.

  11. ASSESSMENT OF LOW-FREQUENCY HEARING WITH NARROW-BAND CHIRP EVOKED 40-HZ SINUSOIDAL AUDITORY STEADY STATE RESPONSE

    PubMed Central

    Wilson, Uzma S.; Kaf, Wafaa A.; Danesh, Ali A.; Lichtenhan, Jeffery T.

    2016-01-01

    Objective To determine the clinical utility of narrow-band chirp evoked 40-Hz sinusoidal auditory steady state responses (s-ASSR) in the assessment of low-frequency hearing in noisy participants. Design Tone bursts and narrow-band chirps were used to respectively evoke auditory brainstem responses (tb-ABR) and 40-Hz s-ASSR thresholds with the Kalman-weighted filtering technique and were compared to behavioral thresholds at 500, 2000, and 4000 Hz. A repeated measure ANOVA and post-hoc t-tests, and simple regression analyses were performed for each of the three stimulus frequencies. Study Sample Thirty young adults aged 18–25 with normal hearing participated in this study. Results When 4000 equivalent responses averages were used, the range of mean s-ASSR thresholds from 500, 2000, and 4000 Hz were 17–22 dB lower (better) than when 2000 averages were used. The range of mean tb-ABR thresholds were lower by 11–15 dB for 2000 and 4000 Hz when twice as many equivalent response averages were used, while mean tb-ABR thresholds for 500 Hz were indistinguishable regardless of additional response averaging Conclusion Narrow band chirp evoked 40-Hz s-ASSR requires a ~15 dB smaller correction factor than tb-ABR for estimating low-frequency auditory threshold in noisy participants when adequate response averaging is used. PMID:26795555

  12. Live CT imaging of sound reception anatomy and hearing measurements in the pygmy killer whale, Feresa attenuata.

    PubMed

    Montie, Eric W; Manire, Charlie A; Mann, David A

    2011-03-15

    In June 2008, two pygmy killer whales (Feresa attenuata) were stranded alive near Boca Grande, FL, USA, and were taken into rehabilitation. We used this opportunity to learn about the peripheral anatomy of the auditory system and hearing sensitivity of these rare toothed whales. Three-dimensional (3-D) reconstructions of head structures from X-ray computed tomography (CT) images revealed mandibles that were hollow, lacked a bony lamina medial to the pan bone and contained mandibular fat bodies that extended caudally and abutted the tympanoperiotic complex. Using auditory evoked potential (AEP) procedures, the modulation rate transfer function was determined. Maximum evoked potential responses occurred at modulation frequencies of 500 and 1000 Hz. The AEP-derived audiograms were U-shaped. The lowest hearing thresholds occurred between 20 and 60 kHz, with the best hearing sensitivity at 40 kHz. The auditory brainstem response (ABR) was composed of seven waves and resembled the ABR of the bottlenose and common dolphins. By changing electrode locations, creating 3-D reconstructions of the brain from CT images and measuring the amplitude of the ABR waves, we provided evidence that the neuroanatomical sources of ABR waves I, IV and VI were the auditory nerve, inferior colliculus and the medial geniculate body, respectively. The combination of AEP testing and CT imaging provided a new synthesis of methods for studying the auditory system of cetaceans.

  13. Short GSM mobile phone exposure does not alter human auditory brainstem response.

    PubMed

    Stefanics, Gábor; Kellényi, Lóránd; Molnár, Ferenc; Kubinyi, Györgyi; Thuróczy, György; Hernádi, István

    2007-11-12

    There are about 1.6 billion GSM cellular phones in use throughout the world today. Numerous papers have reported various biological effects in humans exposed to electromagnetic fields emitted by mobile phones. The aim of the present study was to advance our understanding of potential adverse effects of the GSM mobile phones on the human hearing system. Auditory Brainstem Response (ABR) was recorded with three non-polarizing Ag-AgCl scalp electrodes in thirty young and healthy volunteers (age 18-26 years) with normal hearing. ABR data were collected before, and immediately after a 10 minute exposure to 900 MHz pulsed electromagnetic field (EMF) emitted by a commercial Nokia 6310 mobile phone. Fifteen subjects were exposed to genuine EMF and fifteen to sham EMF in a double blind and counterbalanced order. Possible effects of irradiation was analyzed by comparing the latency of ABR waves I, III and V before and after genuine/sham EMF exposure. Paired sample t-test was conducted for statistical analysis. Results revealed no significant differences in the latency of ABR waves I, III and V before and after 10 minutes of genuine/sham EMF exposure. The present results suggest that, in our experimental conditions, a single 10 minute exposure of 900 MHz EMF emitted by a commercial mobile phone does not produce measurable immediate effects in the latency of auditory brainstem waves I, III and V.

  14. Efficacy/safety of amoxicillin/clavulanate in adults with bacterial rhinosinusitis.

    PubMed

    Anon, Jack B; Berkowitz, Elchonon; Breton, John; Twynholm, Monique

    2006-01-01

    Acute bacterial rhinosinusitis (ABRS) is a common and uncomfortable condition, frequently caused by Streptococcus pneumoniae or Haemophilus influenzae. Antibacterial resistance among these and other common respiratory pathogens is now widespread and of concern. Pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg was developed to be effective against the common respiratory pathogens, including many resistant strains. This open-label, noncomparative study assessed the bacteriologic and clinical efficacy of amoxicillin/clavulanate 2000/125 mg in adult patients with ABRS. Requirements for study entry included a clinical diagnosis of ABRS supported by radiologic findings. In addition, sinus puncture for bacteriologic assessment was required at study entry. Overall, bacteriologic success (eradication or clinical evidence of eradication) at the follow-up visit (days 17-28) was achieved in 87.8% (722/822) of patients with 1 or more pathogen isolated at screening, in 93.2% (246/264) of patients with S pneumoniae, in 96.7% (29/30) of those with penicillin-resistant S pneumoniae (penicillin minimum inhibitory concentrations >or=2 microg/mL), and in 88.7% (110/124) of patients with beta-lactamase-positive pathogens. Bacteriologic success was achieved against 6 of 7 S pneumoniae isolates with amoxicillin/clavulanic acid minimum inhibitory concentrations of 4/2 microg/mL or higher. Amoxicillin/clavulanate 2000/125 mg was generally well tolerated. This new amoxicillin/clavulanate formulation provides a suitable option for empiric therapy for ABRS in adults.

  15. Auditory-steady-state response reliability in the audiological diagnosis after neonatal hearing screening.

    PubMed

    Núñez-Batalla, Faustino; Noriega-Iglesias, Sabel; Guntín-García, Maite; Carro-Fernández, Pilar; Llorente-Pendás, José Luis

    2016-01-01

    Conventional audiometry is the gold standard for quantifying and describing hearing loss. Alternative methods become necessary to assess subjects who are too young to respond reliably. Auditory evoked potentials constitute the most widely used method for determining hearing thresholds objectively; however, this stimulus is not frequency specific. The advent of the auditory steady-state response (ASSR) leads to more specific threshold determination. The current study describes and compares ASSR, auditory brainstem response (ABR) and conventional behavioural tone audiometry thresholds in a group of infants with various degrees of hearing loss. A comparison was made between ASSR, ABR and behavioural hearing thresholds in 35 infants detected in the neonatal hearing screening program. Mean difference scores (±SD) between ABR and high frequency ABR thresholds were 11.2 dB (±13) and 10.2 dB (±11). Pearson correlations between the ASSR and audiometry thresholds were 0.80 and 0.91 (500Hz); 0.84 and 0.82 (1000Hz); 0.85 and 0.84 (2000Hz); and 0.83 and 0.82 (4000Hz). The ASSR technique is a valuable extension of the clinical test battery for hearing-impaired children. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  16. The American Board of Radiology Maintenance of Certification (MOC) Program in Radiologic Physics

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

    Thomas, Stephen R.; Hendee, William R.; Paliwal, Bhudatt R.

    2005-01-01

    Maintenance of Certification (MOC) recognizes that in addition to medical knowledge, several essential elements involved in delivering quality care must be developed and maintained throughout one's career. The MOC process is designed to facilitate and document the professional development of each diplomate of The American Board of Radiology (ABR) through its focus on the essential elements of quality care in Diagnostic Radiology and its subspecialties, and in the specialties of Radiation Oncology and Radiologic Physics. The initial elements of the ABR-MOC have been developed in accord with guidelines of The American Board of Medical Specialties. All diplomates with a ten-year,more » time-limited primary certificate in Diagnostic Radiologic Physics, Therapeutic Radiologic Physics, or Medical Nuclear Physics who wish to maintain certification must successfully complete the requirements of the appropriate ABR-MOC program for their specialty. Holders of multiple certificates must meet ABR-MOC requirements specific to the certificates held. Diplomates with lifelong certificates are not required to participate in the MOC, but are strongly encouraged to do so. MOC is based on documentation of individual participation in the four components of MOC: (1) professional standing, (2) lifelong learning and self-assessment, (3) cognitive expertise, and (4) performance in practice. Within these components, MOC addresses six competencies: medical knowledge, patient care, interpersonal and communication skills, professionalism, practice-based learning and improvement, and systems-based practice.« less

  17. The effect of preterm birth on brainstem, middle latency and cortical auditory evoked responses (BMC AERs).

    PubMed

    Pasman, J W; Rotteveel, J J; de Graaf, R; Stegeman, D F; Visco, Y M

    1992-12-01

    Recent studies on the maturation of auditory brainstem evoked responses (ABRs) present conflicting results, whereas only sparse reports exist with respect to the maturation of middle latency auditory evoked responses (MLRs) and auditory cortical evoked responses (ACRs). The present study reports the effect of preterm birth on the maturation of auditory evoked responses in low risk preterm infants (27-34 weeks conceptional age). The ABRs indicate a consistent trend towards longer latencies for all individual ABR components and towards longer interpeak latencies in preterm infants. The MLR shows longer latencies for early component P0 in preterm infants. The ACRs show a remarkable difference between preterm and term infants. At 40 weeks CA the latencies of ACR components Na and P2 are significantly longer in term infants, whereas at 52 weeks CA the latencies of the same ACR components are shorter in term infants. The results support the hypothesis that retarded myelination of the central auditory pathway is partially responsible for differences found between preterm infants and term infants with respect to late ABR components and early MLR component P0. Furthermore, mild conductive hearing loss in preterm infants may also play its role. A more complex mechanism is implicated to account for the findings noted with respect to MLR component Na and ACR components Na and P2.

  18. From cooperation to conflict? Swedish rehabilitation professionals' experiences of interorganizational cooperation.

    PubMed

    Ståhl, Christian; Svensson, Tommy; Ekberg, Kerstin

    2011-09-01

    This article analyses Swedish rehabilitation professionals' experiences of interorganizational cooperation in return-to-work and labour market reintegration. Two groups (n = 15) from different organizations met on a regular basis to discuss their practice from a cooperation perspective. The participants had experience of cooperation in the organizational setting of Coordination Associations. The groups worked with a tutor according to a problem-based methodology, to discuss how their practice is influenced by new structures for cooperation. The material was analysed inductively using qualitative content analysis. Interorganizational cooperation in rehabilitation is generally perceived as promoting coherence and communication. Nevertheless, there are several contradictory factors in the implementation of such work forms, primarily inflexible sickness insurance regulations and inability of managers to implement cooperation in regular practice. While interorganizational cooperation promotes professional discretion and tailored solutions, the insurance system contradicts such ambitions through increased governance. Ultimately, the contradictory tendencies of cooperative initiatives and the stricter governance of sickness insurance regulations are political matters. If political attempts to promote interorganizational cooperation are to succeed, the increasing sectorization that results from strict governance of sickness insurance regulations needs to be targeted on a system level.

  19. The Rose (Rosa hybrida) NAC Transcription Factor 3 Gene, RhNAC3, Involved in ABA Signaling Pathway Both in Rose and Arabidopsis

    PubMed Central

    Lü, Peitao; Liu, Jitao; Gao, Junping; Zhang, Changqing

    2014-01-01

    Plant transcription factors involved in stress responses are generally classified by their involvement in either the abscisic acid (ABA)-dependent or the ABA-independent regulatory pathways. A stress-associated NAC gene from rose (Rosa hybrida), RhNAC3, was previously found to increase dehydration tolerance in both rose and Arabidopsis. However, the regulatory mechanism involved in RhNAC3 action is still not fully understood. In this study, we isolated and analyzed the upstream regulatory sequence of RhNAC3 and found many stress-related cis-elements to be present in the promoter, with five ABA-responsive element (ABRE) motifs being of particular interest. Characterization of Arabidopsis thaliana plants transformed with the putative RhNAC3 promoter sequence fused to the β-glucuronidase (GUS) reporter gene revealed that RhNAC3 is expressed at high basal levels in leaf guard cells and in vascular tissues. Moreover, the ABRE motifs in the RhNAC3 promoter were observed to have a cumulative effect on the transcriptional activity of this gene both in the presence and absence of exogenous ABA. Overexpression of RhNAC3 in A. thaliana resulted in ABA hypersensitivity during seed germination and promoted leaf closure after ABA or drought treatments. Additionally, the expression of 11 ABA-responsive genes was induced to a greater degree by dehydration in the transgenic plants overexpressing RhNAC3 than control lines transformed with the vector alone. Further analysis revealed that all these genes contain NAC binding cis-elements in their promoter regions, and RhNAC3 was found to partially bind to these putative NAC recognition sites. We further found that of 219 A. thaliana genes previously shown by microarray analysis to be regulated by heterologous overexpression RhNAC3, 85 are responsive to ABA. In rose, the expression of genes downstream of the ABA-signaling pathways was also repressed in RhNAC3-silenced petals. Taken together, we propose that the rose RhNAC3 protein could mediate ABA signaling both in rose and in A. thaliana. PMID:25290154

  20. The rose (Rosa hybrida) NAC transcription factor 3 gene, RhNAC3, involved in ABA signaling pathway both in rose and Arabidopsis.

    PubMed

    Jiang, Guimei; Jiang, Xinqiang; Lü, Peitao; Liu, Jitao; Gao, Junping; Zhang, Changqing

    2014-01-01

    Plant transcription factors involved in stress responses are generally classified by their involvement in either the abscisic acid (ABA)-dependent or the ABA-independent regulatory pathways. A stress-associated NAC gene from rose (Rosa hybrida), RhNAC3, was previously found to increase dehydration tolerance in both rose and Arabidopsis. However, the regulatory mechanism involved in RhNAC3 action is still not fully understood. In this study, we isolated and analyzed the upstream regulatory sequence of RhNAC3 and found many stress-related cis-elements to be present in the promoter, with five ABA-responsive element (ABRE) motifs being of particular interest. Characterization of Arabidopsis thaliana plants transformed with the putative RhNAC3 promoter sequence fused to the β-glucuronidase (GUS) reporter gene revealed that RhNAC3 is expressed at high basal levels in leaf guard cells and in vascular tissues. Moreover, the ABRE motifs in the RhNAC3 promoter were observed to have a cumulative effect on the transcriptional activity of this gene both in the presence and absence of exogenous ABA. Overexpression of RhNAC3 in A. thaliana resulted in ABA hypersensitivity during seed germination and promoted leaf closure after ABA or drought treatments. Additionally, the expression of 11 ABA-responsive genes was induced to a greater degree by dehydration in the transgenic plants overexpressing RhNAC3 than control lines transformed with the vector alone. Further analysis revealed that all these genes contain NAC binding cis-elements in their promoter regions, and RhNAC3 was found to partially bind to these putative NAC recognition sites. We further found that of 219 A. thaliana genes previously shown by microarray analysis to be regulated by heterologous overexpression RhNAC3, 85 are responsive to ABA. In rose, the expression of genes downstream of the ABA-signaling pathways was also repressed in RhNAC3-silenced petals. Taken together, we propose that the rose RhNAC3 protein could mediate ABA signaling both in rose and in A. thaliana.

  1. Sugar for the brain: the role of glucose in physiological and pathological brain function.

    PubMed

    Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A; Meisel, Andreas

    2013-10-01

    The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We synthesize these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation that lead to disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Dose and time dependent ototoxicity of aspartame in rats.

    PubMed

    Ozturan, Orhan; Dogan, Remzi; Tugrul, Selahattin; Gedik, Ozge; Sjostrand, Alev Pektas; Yildirim, Yavuz Selim

    2017-04-01

    Low-dose administration of Aspartame (Ap) did not produce a significant ototoxic effect at the end of the 6th month. However, duration of the ototoxic effect is shortened and severity of the effect is increased as dose and duration of Ap administration is increased. While Ap toxicity has been studied in short- and long-term studies, its effects on hearing have not been investigated. This study was conducted to evaluate the effects of long-term consumption of Ap administered in various doses on hearing status of rats. The study included 54 female Wistar Albino rats. Ap was given for 6 months to the rats. The groups were assigned according to levels of Ap dosage. DPOAE and ABR tests were utilized for serial hearing evaluations. Serial hearing measurement times were designed as baseline, 1st week, 2nd week, 1st, 2nd, 3rd, and 6th months. While audiological parameters deteriorated with 100 mg/kg/day dose after the 3rd month, ABR thresholds were elevated and DPOAE values were significantly decreased in 500 mg/kg/day and 1000 mg/kg/day applications after the 2nd month. In 2000 mg/kg/day and 4000 mg/kg/day applications, deteriorations in audiological parameters were detected as early as the first and second months; respectively.

  3. Differential baroreflex control of heart rate in sedentary and aerobically fit individuals

    NASA Technical Reports Server (NTRS)

    Smith, S. A.; Querry, R. G.; Fadel, P. J.; Welch-O'Connor, R. M.; Olivencia-Yurvati, A.; Shi, X.; Raven, P. B.

    2000-01-01

    PURPOSE: We compared arterial, aortic, and carotid-cardiac baroreflex sensitivity in eight average fit (maximal oxygen uptake, VO2max = 42.2+/-1.9 mL x kg(-1) x min(-1)) and eight high fit (VO2max = 61.9+/-2.2 mL x kg(-1) x min(-1)) healthy young adults. METHODS: Arterial and aortic (ABR) baroreflex functions were assessed utilizing hypo- and hyper-tensive challenges induced by graded bolus injections of sodium nitroprusside (SN) and phenylephrine (PE), respectively. Carotid baroreflex (CBR) sensitivity was determined using ramped 5-s pulses of both pressure and suction delivered to the carotid sinus via a neck chamber collar, independent of drug administration. RESULTS: During vasoactive drug injection, mean arterial pressure (MAP) was similarly altered in average fit (AF) and high fit (HF) groups. However, the heart rate (HR) response range of the arterial baroreflex was significantly attenuated (P < 0.05) in HF (31+/-4 beats x min(-1)) compared with AF individuals (46+/-4 beats x min(-1)). When sustained neck suction and pressure were applied to counteract altered carotid sinus pressure during SN and PE administration, isolating the ABR response, the response range remained diminished (P < 0.05) in the HF population (24+/-3 beats x min(-1)) compared with the AF group (41+/-4 beats x min(-1)). During CBR perturbation, the HF (14+/-1 beats-min(-1)) and AF (16+/-1 beats-min(-1)) response ranges were similar. The arterial baroreflex response range was significantly less than the simple sum of the CBR and ABR (HF, 38+/-3 beats x min(-1) and AF, 57+/-4 beats x min(-1)) in both fitness groups. CONCLUSIONS: These data confirm that reductions in arterial-cardiac reflex sensitivity are mediated by diminished ABR function. More importantly, these data suggest that the integrative relationship between the ABR and CBR contributing to arterial baroreflex control of HR is inhibitory in nature and not altered by exercise training.

  4. Prophylaxis vs. on-demand treatment with BAY 81-8973, a full-length plasma protein-free recombinant factor VIII product: results from a randomized trial (LEOPOLD II).

    PubMed

    Kavakli, K; Yang, R; Rusen, L; Beckmann, H; Tseneklidou-Stoeter, D; Maas Enriquez, M

    2015-03-01

    BAY 81-8973 is a new full-length human recombinant factor VIII product manufactured with technologies to improve consistency in glycosylation and expression to optimize clinical performance. To demonstrate superiority of prophylaxis vs. on demand therapy with BAY 81-8973 in patients with severe hemophilia A. In this multinational,randomized, open-label crossover study (LEOPOLD II;ClinicalTrials.gov identifier: NCT01233258), males aged 12–65 years with severe hemophilia A were randomized to twice-weekly prophylaxis (20-30 IU kg(-1)), 3-times-weekly prophylaxis (30-40 IU kg(-1)), or on-demand treatment with BAY 81-8973. Potency labeling for BAY 81-8973 was based on the chromogenic substrate assay or adjusted to the one-stage assay. Primary efficacy endpoint was annualized number of all bleeds (ABR). Adverse events (AEs)and immunogenicity were also assessed. Eighty patients (on demand, n = 21; twice-weekly prophylaxis, n = 28; 3-times-weekly prophylaxis, n = 31) were treated and analyzed. Mean ± SD ABR was significantly lower with prophylaxis (twice-weekly, 5.7 ± 7.2; 3-times-weekly, 4.3 ± 6.5; combined, 4.9 ± 6.8) vs. on-demand treatment (57.7 ± 24.6; P < 0.0001, ANOVA). Median ABR was reduced by 97% with prophylaxis (twice-weekly, 4.0;3-times-weekly, 2.0; combined, 2.0) vs. on-demand treatment (60.0). Median ABR was higher with twice-weekly vs. 3-times-weekly prophylaxis during the first 6-month treatment period (4.1 vs. 2.0) but was comparable in the second 6-month period (1.1 vs. 2.0). Few patients reported treatment-related AEs (4%); no treatment-related serious AEs or inhibitors were reported. Twice weekly or 3-times-weekly prophylaxis with BAY 81-8973 reduced median ABR by 97% compared with on-demand therapy, confirming the superiority of prophylaxis. Treatment with BAY 81-8973 was well tolerated.

  5. The Binaural Interaction Component in Barn Owl (Tyto alba) Presents few Differences to Mammalian Data.

    PubMed

    Palanca-Castan, Nicolas; Laumen, Geneviève; Reed, Darrin; Köppl, Christine

    2016-12-01

    The auditory brainstem response (ABR) is an evoked potential that reflects the responses to sound by brainstem neural centers. The binaural interaction component (BIC) is obtained by subtracting the sum of the monaural ABR responses from the binaural response. Its latency and amplitude change in response to variations in binaural cues. The BIC is thus thought to reflect the activity of binaural nuclei and is used to non-invasively test binaural processing. However, any conclusions are limited by a lack of knowledge of the relevant processes at the level of individual neurons. The aim of this study was to characterize the ABR and BIC in the barn owl, an animal where the ITD-processing neural circuits are known in great detail. We recorded ABR responses to chirps and to 1 and 4 kHz tones from anesthetized barn owls. General characteristics of the barn owl ABR were similar to those observed in other bird species. The most prominent peak of the BIC was associated with nucleus laminaris and is thus likely to reflect the known processes of ITD computation in this nucleus. However, the properties of the BIC were very similar to previously published mammalian data and did not reveal any specific diagnostic features. For example, the polarity of the BIC was negative, which indicates a smaller response to binaural stimulation than predicted by the sum of monaural responses. This is contrary to previous predictions for an excitatory-excitatory system such as nucleus laminaris. Similarly, the change in BIC latency with varying ITD was not distinguishable from mammalian data. Contrary to previous predictions, this behavior appears unrelated to the known underlying neural delay-line circuitry. In conclusion, the generation of the BIC is currently inadequately understood and common assumptions about the BIC need to be reconsidered when interpreting such measurements.

  6. AH-64D Apache Longbow/Video from UAS for Interoperability Teaming Level II (VUIT-2) Aircrew Workload Assessment

    DTIC Science & Technology

    2009-04-01

    ABR Page 501.9 3% Show Page 138.7 1% Ctrlm Page 500.7 3% Point Page 99.3 1% DTU Page 392.2 2% Load Page 49.3 ə% Flt Page 231.7 1% Video...7573.4 87% Eng Page 835.4 10% Route Menu Page 335.8 4% Flt Page 709 9% DTU Page 327.5 4% ABR Page 458.9 6% Test Status Page 160.3 2% ASE

  7. The role of CT in professionalism: accreditation, certification and the welfare of our children.

    PubMed

    Frush, Donald P

    2011-09-01

    Defining, measuring and promoting professionalism in medicine, including radiology, has been increasingly emphasized by organizations such as ACGME, the ACR and ABR. It is clear that we as imaging experts have as an ultimate responsibility the welfare of our patients. This is the essence of professionalism, and major societies such as the ACR, ABR and RSNA are embracing professionalism through ongoing safety and training efforts. Some of those efforts in accreditation of equipment and certification of medical professionals will be discussed.

  8. Four cases of acoustic neuromas with normal hearing.

    PubMed

    Valente, M; Peterein, J; Goebel, J; Neely, J G

    1995-05-01

    In 95 percent of the cases, patients with acoustic neuromas will have some magnitude of hearing loss in the affected ear. This paper reports on four patients who had acoustic neuromas and normal hearing. Results from the case history, audiometric evaluation, auditory brainstem response (ABR), electroneurography (ENOG), and vestibular evaluation are reported for each patient. For all patients, the presence of unilateral tinnitus was the most common complaint. Audiologically, elevated or absent acoustic reflex thresholds and abnormal ABR findings were the most powerful diagnostic tools.

  9. 7 CFR 4285.93 - Other Federal statutes and regulations that apply.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE COOPERATIVE AGREEMENTS Federal-State Research on Cooperatives Program § 4285.93 Other Federal statutes and regulations that apply...—National Agricultural, Research, Extension, and Teaching Policy Act Amendments of 1981 if the project...

  10. 48 CFR 702.170-5 - Cooperating country national (CCN).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Cooperating country national (CCN). 702.170-5 Section 702.170-5 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL DEVELOPMENT GENERAL DEFINITIONS OF WORDS AND TERMS Definitions 702.170-5 Cooperating country national (CCN...

  11. Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner.

    PubMed

    Dragone, Leonard L; Myers, Margaret D; White, Carmen; Gadwal, Shyam; Sosinowski, Tomasz; Gu, Hua; Weiss, Arthur

    2006-11-28

    Src-like adaptor protein (SLAP) and c-Cbl recently have been shown to cooperate in regulating T cell receptor (TCR) levels in developing T cells. SLAP also is expressed in developing B cells, and its deficiency leads to alterations in B cell receptor (BCR) levels and B cell development. Hence, we hypothesized that SLAP and c-Cbl may cooperate during B cell development to regulate BCR levels. In mice deficient in both SLAP and c-Cbl, we found that B cell development is altered, suggesting that they function through intersecting pathways. To study the mechanism by which SLAP and c-Cbl alter BCR levels, we coexpressed them in a mature mouse B cell line (Bal-17). First we determined that SLAP associates with proximal components of the BCR complex after stimulation and internalization. Coexpression of SLAP and c-Cbl in Bal-17 led to decreased surface and total BCR levels. This decrease in BCR levels depended on intact Src homology 2 (SH2) and C-terminal domains of SLAP. In addition, a mutation in the SH2 domain of SLAP blocked its colocalization with c-Cbl and the BCR complex, whereas deletion of the C terminus did not affect its localization. Last, coexpression of SLAP and c-Cbl altered BCR complex recycling. This alteration in BCR complex recycling depended on enzymatically active c-Cbl and Src family kinases, as well as the intact SH2 and C-terminal domains of SLAP. These data suggest that SLAP has a conserved function in B and T cells by adapting c-Cbl to the antigen-receptor complex and targeting it for degradation.

  12. Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner

    PubMed Central

    Dragone, Leonard L.; Myers, Margaret D.; White, Carmen; Gadwal, Shyam; Sosinowski, Tomasz; Gu, Hua; Weiss, Arthur

    2006-01-01

    Src-like adaptor protein (SLAP) and c-Cbl recently have been shown to cooperate in regulating T cell receptor (TCR) levels in developing T cells. SLAP also is expressed in developing B cells, and its deficiency leads to alterations in B cell receptor (BCR) levels and B cell development. Hence, we hypothesized that SLAP and c-Cbl may cooperate during B cell development to regulate BCR levels. In mice deficient in both SLAP and c-Cbl, we found that B cell development is altered, suggesting that they function through intersecting pathways. To study the mechanism by which SLAP and c-Cbl alter BCR levels, we coexpressed them in a mature mouse B cell line (Bal-17). First we determined that SLAP associates with proximal components of the BCR complex after stimulation and internalization. Coexpression of SLAP and c-Cbl in Bal-17 led to decreased surface and total BCR levels. This decrease in BCR levels depended on intact Src homology 2 (SH2) and C-terminal domains of SLAP. In addition, a mutation in the SH2 domain of SLAP blocked its colocalization with c-Cbl and the BCR complex, whereas deletion of the C terminus did not affect its localization. Last, coexpression of SLAP and c-Cbl altered BCR complex recycling. This alteration in BCR complex recycling depended on enzymatically active c-Cbl and Src family kinases, as well as the intact SH2 and C-terminal domains of SLAP. These data suggest that SLAP has a conserved function in B and T cells by adapting c-Cbl to the antigen-receptor complex and targeting it for degradation. PMID:17110436

  13. Phosphorylation acts positively and negatively to regulate MRTF-A subcellular localisation and activity

    PubMed Central

    Panayiotou, Richard; Miralles, Francesc; Pawlowski, Rafal; Diring, Jessica; Flynn, Helen R; Skehel, Mark; Treisman, Richard

    2016-01-01

    The myocardin-related transcription factors (MRTF-A and MRTF-B) regulate cytoskeletal genes through their partner transcription factor SRF. The MRTFs bind G-actin, and signal-regulated changes in cellular G-actin concentration control their nuclear accumulation. The MRTFs also undergo Rho- and ERK-dependent phosphorylation, but the function of MRTF phosphorylation, and the elements and signals involved in MRTF-A nuclear export are largely unexplored. We show that Rho-dependent MRTF-A phosphorylation reflects relief from an inhibitory function of nuclear actin. We map multiple sites of serum-induced phosphorylation, most of which are S/T-P motifs and show that S/T-P phosphorylation is required for transcriptional activation. ERK-mediated S98 phosphorylation inhibits assembly of G-actin complexes on the MRTF-A regulatory RPEL domain, promoting nuclear import. In contrast, S33 phosphorylation potentiates the activity of an autonomous Crm1-dependent N-terminal NES, which cooperates with five other NES elements to exclude MRTF-A from the nucleus. Phosphorylation thus plays positive and negative roles in the regulation of MRTF-A. DOI: http://dx.doi.org/10.7554/eLife.15460.001 PMID:27304076

  14. The Hard Problem of Cooperation

    PubMed Central

    Eriksson, Kimmo; Strimling, Pontus

    2012-01-01

    Based on individual variation in cooperative inclinations, we define the “hard problem of cooperation” as that of achieving high levels of cooperation in a group of non-cooperative types. Can the hard problem be solved by institutions with monitoring and sanctions? In a laboratory experiment we find that the answer is affirmative if the institution is imposed on the group but negative if development of the institution is left to the group to vote on. In the experiment, participants were divided into groups of either cooperative types or non-cooperative types depending on their behavior in a public goods game. In these homogeneous groups they repeatedly played a public goods game regulated by an institution that incorporated several of the key properties identified by Ostrom: operational rules, monitoring, rewards, punishments, and (in one condition) change of rules. When change of rules was not possible and punishments were set to be high, groups of both types generally abided by operational rules demanding high contributions to the common good, and thereby achieved high levels of payoffs. Under less severe rules, both types of groups did worse but non-cooperative types did worst. Thus, non-cooperative groups profited the most from being governed by an institution demanding high contributions and employing high punishments. Nevertheless, in a condition where change of rules through voting was made possible, development of the institution in this direction was more often voted down in groups of non-cooperative types. We discuss the relevance of the hard problem and fit our results into a bigger picture of institutional and individual determinants of cooperative behavior. PMID:22792282

  15. Multiple Mechanisms Cooperate to Constitutively Exclude the Transcriptional Co-Activator YAP from the Nucleus During Murine Oogenesis1

    PubMed Central

    Abbassi, Laleh; Malki, Safia; Cockburn, Katie; Macaulay, Angus; Robert, Claude; Rossant, Janet; Clarke, Hugh J.

    2016-01-01

    Reproduction depends on the generation of healthy oocytes. Improving therapeutic strategies to prolong or rescue fertility depends on identifying the inter- and intracellular mechanisms that direct oocyte development under physiological conditions. Growth and proliferation of multiple cell types is regulated by the Hippo signaling pathway, whose chief effectors are the transcriptional co-activator YAP and its paralogue WWTR1. To resolve conflicting results concerning the potential role of Hippo in mammalian oocyte development, we systematically investigated the expression and localization of YAP in mouse oocytes. We report that that YAP is expressed in the germ cells beginning as early as Embryonic Day 15.5 and subsequently throughout pre- and postnatal oocyte development. However, YAP is restricted to the cytoplasm at all stages. YAP is phosphorylated at serine-112 in growing and fully grown oocytes, identifying a likely mechanistic basis for its nuclear exclusion, and becomes dephosphorylated at this site during meiotic maturation. Phosphorylation at serine-112 is regulated by a mechanism dependent on cyclic AMP and protein kinase A, which is known to be active in oocytes prior to maturation. Growing oocytes also contain a subpopulation of YAP, likely dephosphorylated, that is able enter the oocyte nucleus, but it is not retained there, implying that oocytes lack the cofactors required to retain YAP in the nucleus. Thus, although YAP is expressed throughout oocyte development, phosphorylation-dependent and -independent mechanisms cooperate to ensure that it does not accumulate in the nucleus. We conclude that nuclear YAP does not play a significant physiological role during oocyte development in mammals. PMID:26985001

  16. 78 FR 68376 - Removal of Procedures for Delegation of Administration of Grants and Cooperative Agreements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-14

    ... Procedures for Delegation of Administration of Grants and Cooperative Agreements AGENCY: National Aeronautics... regulation agency procedures for the delegation of administration of grants and cooperative agreements. Simultaneous with the removal of the delegation of administration procedures from the regulation, NASA will...

  17. Dependency links can hinder the evolution of cooperation in the prisoner's dilemma game on lattices and networks.

    PubMed

    Wang, Xuwen; Nie, Sen; Wang, Binghong

    2015-01-01

    Networks with dependency links are more vulnerable when facing the attacks. Recent research also has demonstrated that the interdependent groups support the spreading of cooperation. We study the prisoner's dilemma games on spatial networks with dependency links, in which a fraction of individual pairs is selected to depend on each other. The dependency individuals can gain an extra payoff whose value is between the payoff of mutual cooperation and the value of temptation to defect. Thus, this mechanism reflects that the dependency relation is stronger than the relation of ordinary mutual cooperation, but it is not large enough to cause the defection of the dependency pair. We show that the dependence of individuals hinders, promotes and never affects the cooperation on regular ring networks, square lattice, random and scale-free networks, respectively. The results for the square lattice and regular ring networks are demonstrated by the pair approximation.

  18. Brain stem audiometry may supply markers for diagnostic and therapeutic control in psychiatry.

    PubMed

    Nielzén, Sören; Holmberg, Jens; Sköld, Mia; Nehlstedt, Sara

    2016-10-06

    The purpose of the present study is to try an alternative way of analyzing the ABR (Auditory Brainstem Response). The stimuli were complex sounds (c-ABR) as used in earlier studies. It was further aimed at corroborating earlier findings that this method can discriminate several neuropsychiatric states. Forty healthy control subjects, 26 subjects with the diagnosis schizophrenia (Sz) and 33 with ADHD (Attention deficit hyperactivity disorder) were recruited for the study. The ABRs were recorded. The analysis was based on calculation of areas of significantly group different time spans in the waves. Both latency and amplitude were thereby influential. The spans of differences were quantified for each subject in relation to the total area of the curve which made comparisons balanced. The results showed highly significant differences between the study groups. The results are important for future work on identifying markers for neuropsychiatric clinical use. To reach that goal calls for more extensive studies than this preliminary one. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. High-rate anaerobic treatment system for solid/lipid-rich wastewater using anaerobic baffled reactor with scum recovery.

    PubMed

    Fujihira, Takuya; Seo, Shogo; Yamaguchi, Takashi; Hatamoto, Masashi; Tanikawa, Daisuke

    2018-04-27

    A laboratory scale experiment was conducted to investigate the treatment of solid/lipid-rich wastewater with an anaerobic baffled reactor (ABR) and a down-flow hanging sponge (DHS) reactor. In this study, experimental periods were divided into three phases to explore efficient treatment of solids and lipids in wastewater. In ABR, >90% of the influent chemical oxygen demand (COD) was removed and >70% of the removed COD was converted to methane under steady-state conditions during each phase. During this period, >4.5 kg COD m -3  d -1 was achieved on an average in Phases 1 and 3. Biogas contributed to scum formation, and the scum was categorized into lipid-rich and sludge-containing types, which have energy potentials of 53.4 and 212 kcal/kg-wet weight, respectively. Therefore, by recovering solids and lipids, which formed persistent scum, ABR can be applied as a high-rate treatment for solid/lipid-rich wastewater. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. The startup performance and microbial distribution of an anaerobic baffled reactor (ABR) treating medium-strength synthetic industrial wastewater.

    PubMed

    Jiang, Hao; Nie, Hong; Ding, Jiangtao; Stinner, Walter; Sun, Kaixuan; Zhou, Hongjun

    2018-01-02

    In this study, an anaerobic baffled reactor (ABR) with seven chambers was applied to treat medium-strength synthetic industrial wastewater (MSIW). The performance of startup and shock test on treating MSIW was investigated. During the acclimation process, the chemical oxygen demand (COD) of MSIW gradually increased from 0 to 2,000 mg L -1 , and the COD removal finally reached 90%. At shock test, the feeding COD concentration increased by one-fifth and the reactor adapted very well with a COD removal of 82%. In a stable state, Comamonas, Smithella, Syntrophomonas and Pseudomonas were the main populations of bacteria, while the predominant methanogen was Methanobacterium. The results of chemical and microbiological analysis indicated the significant advantages of ABR, including buffering shocks, separating stages with matching microorganisms and promoting syntrophism. Meanwhile, the strategies for acclimation and operation were of great importance. Further work can test reactor performance in the treatment of actual industrial wastewater.

  1. Human inferior colliculus activity relates to individual differences in spoken language learning.

    PubMed

    Chandrasekaran, Bharath; Kraus, Nina; Wong, Patrick C M

    2012-03-01

    A challenge to learning words of a foreign language is encoding nonnative phonemes, a process typically attributed to cortical circuitry. Using multimodal imaging methods [functional magnetic resonance imaging-adaptation (fMRI-A) and auditory brain stem responses (ABR)], we examined the extent to which pretraining pitch encoding in the inferior colliculus (IC), a primary midbrain structure, related to individual variability in learning to successfully use nonnative pitch patterns to distinguish words in American English-speaking adults. fMRI-A indexed the efficiency of pitch representation localized to the IC, whereas ABR quantified midbrain pitch-related activity with millisecond precision. In line with neural "sharpening" models, we found that efficient IC pitch pattern representation (indexed by fMRI) related to superior neural representation of pitch patterns (indexed by ABR), and consequently more successful word learning following sound-to-meaning training. Our results establish a critical role for the IC in speech-sound representation, consistent with the established role for the IC in the representation of communication signals in other animal models.

  2. In vivo collective cell migration requires an LPAR2-dependent increase in tissue fluidity

    PubMed Central

    Kuriyama, Sei; Theveneau, Eric; Benedetto, Alexandre; Parsons, Maddy; Tanaka, Masamitsu; Charras, Guillaume; Kabla, Alexandre

    2014-01-01

    Collective cell migration (CCM) and epithelial–mesenchymal transition (EMT) are common to cancer and morphogenesis, and are often considered to be mutually exclusive in spite of the fact that many cancer and embryonic cells that have gone through EMT still cooperate to migrate collectively. Here we use neural crest (NC) cells to address the question of how cells that have down-regulated cell–cell adhesions can migrate collectively. NC cell dissociation relies on a qualitative and quantitative change of the cadherin repertoire. We found that the level of cell–cell adhesion is precisely regulated by internalization of N-cadherin downstream of lysophosphatidic acid (LPA) receptor 2. Rather than promoting the generation of single, fully mesenchymal cells, this reduction of membrane N-cadherin only triggers a partial mesenchymal phenotype. This intermediate phenotype is characterized by an increase in tissue fluidity akin to a solid-like–to–fluid-like transition. This change of plasticity allows cells to migrate under physical constraints without abolishing cell cooperation required for collectiveness. PMID:25002680

  3. Structure and mechanisms of Escherichia coli aspartate transcarbamoylase.

    PubMed

    Lipscomb, William N; Kantrowitz, Evan R

    2012-03-20

    Enzymes catalyze a particular reaction in cells, but only a few control the rate of this reaction and the metabolic pathway that follows. One specific mechanism for such enzymatic control of a metabolic pathway involves molecular feedback, whereby a metabolite further down the pathway acts at a unique site on the control enzyme to alter its activity allosterically. This regulation may be positive or negative (or both), depending upon the particular system. Another method of enzymatic control involves the cooperative binding of the substrate, which allows a large change in enzyme activity to emanate from only a small change in substrate concentration. Allosteric regulation and homotropic cooperativity are often known to involve significant conformational changes in the structure of the protein. Escherichia coli aspartate transcarbamoylase (ATCase) is the textbook example of an enzyme that regulates a metabolic pathway, namely, pyrimidine nucleotide biosynthesis, by feedback control and by the cooperative binding of the substrate, L-aspartate. The catalytic and regulatory mechanisms of this enzyme have been extensively studied. A series of X-ray crystal structures of the enzyme in the presence and absence of substrates, products, and analogues have provided details, at the molecular level, of the conformational changes that the enzyme undergoes as it shifts between its low-activity, low-affinity form (T state) to its high-activity, high-affinity form (R state). These structural data provide insights into not only how this enzyme catalyzes the reaction between l-aspartate and carbamoyl phosphate to form N-carbamoyl-L-aspartate and inorganic phosphate, but also how the allosteric effectors modulate this activity. In this Account, we summarize studies on the structure of the enzyme and describe how these structural data provide insights into the catalytic and regulatory mechanisms of the enzyme. The ATCase-catalyzed reaction is regulated by nucleotide binding some 60 Å from the active site, inducing structural alterations that modulate catalytic activity. The delineation of the structure and function in this particular model system will help in understanding the molecular basis of cooperativity and allosteric regulation in other systems as well.

  4. 7 CFR 4285.1 - Objective.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE COOPERATIVE AGREEMENTS Federal-State Research on Cooperatives... for providing Federal-State Research on Cooperatives cooperative agreement funds to finance programs...

  5. Clinical and economic impact of antibiotic resistance in developing countries: A systematic review and meta-analysis.

    PubMed

    Founou, Raspail Carrel; Founou, Luria Leslie; Essack, Sabiha Yusuf

    2017-01-01

    Despite evidence of the high prevalence of antibiotic resistant infections in developing countries, studies on the clinical and economic impact of antibiotic resistance (ABR) to inform interventions to contain its emergence and spread are limited. The aim of this study was to analyze the published literature on the clinical and economic implications of ABR in developing countries. A systematic search was carried out in Medline via PubMed and Web of Sciences and included studies published from January 01, 2000 to December 09, 2016. All papers were considered and a quality assessment was performed using the Newcastle-Ottawa quality assessment scale (NOS). Of 27 033 papers identified, 40 studies met the strict inclusion and exclusion criteria and were finally included in the qualitative and quantitative analysis. Mortality was associated with resistant bacteria, and statistical significance was evident with an odds ratio (OR) 2.828 (95%CI, 2.231-3.584; p = 0.000). ESKAPE pathogens was associated with the highest risk of mortality and with high statistical significance (OR 3.217; 95%CIs; 2.395-4.321; p = 0.001). Eight studies showed that ABR, and especially antibiotic-resistant ESKAPE bacteria significantly increased health care costs. ABR is associated with a high mortality risk and increased economic costs with ESKAPE pathogens implicated as the main cause of increased mortality. Patients with non-communicable disease co-morbidities were identified as high-risk populations.

  6. Clinical and economic impact of antibiotic resistance in developing countries: A systematic review and meta-analysis

    PubMed Central

    Founou, Luria Leslie; Essack, Sabiha Yusuf

    2017-01-01

    Introduction Despite evidence of the high prevalence of antibiotic resistant infections in developing countries, studies on the clinical and economic impact of antibiotic resistance (ABR) to inform interventions to contain its emergence and spread are limited. The aim of this study was to analyze the published literature on the clinical and economic implications of ABR in developing countries. Methods A systematic search was carried out in Medline via PubMed and Web of Sciences and included studies published from January 01, 2000 to December 09, 2016. All papers were considered and a quality assessment was performed using the Newcastle-Ottawa quality assessment scale (NOS). Results Of 27 033 papers identified, 40 studies met the strict inclusion and exclusion criteria and were finally included in the qualitative and quantitative analysis. Mortality was associated with resistant bacteria, and statistical significance was evident with an odds ratio (OR) 2.828 (95%CI, 2.231–3.584; p = 0.000). ESKAPE pathogens was associated with the highest risk of mortality and with high statistical significance (OR 3.217; 95%CIs; 2.395–4.321; p = 0.001). Eight studies showed that ABR, and especially antibiotic-resistant ESKAPE bacteria significantly increased health care costs. Conclusion ABR is associated with a high mortality risk and increased economic costs with ESKAPE pathogens implicated as the main cause of increased mortality. Patients with non-communicable disease co-morbidities were identified as high-risk populations. PMID:29267306

  7. Treatment of low-strength soluble wastewater using an anaerobic baffled reactor (ABR).

    PubMed

    Gopala Krishna, G V T; Kumar, Pramod; Kumar, Pradeep

    2009-01-01

    Treatment of low-strength soluble wastewater (COD approximately 500 mg/L) was studied using an eight chambered anaerobic baffled reactor (ABR). At pseudo steady-state (PSS), the average total and soluble COD values (COD(T) and COD(S)) at 8h hydraulic retention time (HRT) were found to be around 50 and 40 mg/L, respectively, while at 10h HRT average COD(T) and COD(S) values were of the order of 47 and 37 mg/L, respectively. COD and BOD (3 day, 27 degrees C) removal averaged more than 90%. Effluent conformed to Indian standards laid down for BOD (less than 30 mg/L). Reactor effluent characteristics exhibited very low values of standard deviation indicating excellent reactor stability at PSS in terms of effluent characteristics. Based on mass balance calculations, more than 60% of raw wastewater COD was estimated to be recovered as CH(4) in the gas phase. Compartment-wise profiles indicated that most of the BOD and COD got reduced in the initial compartments only. Sudden drop in pH (7.8-6.7) and formation of volatile fatty acids (VFA) (53-85 mg/L) were observed in the first compartment due to acidogenesis and acetogenesis. The pH increased and VFA concentration decreased longitudinally down the reactor. Residence time distribution (RTD) studies revealed that the flow pattern in the ABR was neither completely plug-flow nor perfectly mixed. Observations from scanning electron micrographs (SEM) suggest that distinct phase separation takes place in an ABR.

  8. Prediction of permanent hearing loss in high-risk preterm infants at term age.

    PubMed

    Valkama, A M; Laitakari, K T; Tolonen, E U; Väyrynen, M R; Vainionpää, L K; Koivisto, M E

    2000-06-01

    The aim of this series was to assess hearing screenings; auditory brainstem responses (ABR), transient evoked otoacoustic emissions (TEOAE) and free field auditory responses (FF) for the prediction of permanent bilateral hearing loss in high-risk preterm infants at term post-conceptional age. A total of 51 preterm infants (gestational age < 34 weeks, birth weight < 1500 g) underwent examinations at term and hearing, speech and neurological development were followed up until a corrected age of 18 months. Significant hearing defects were verified by broader ABR examinations under sedation and by clinical ward observation including responsiveness to sounds and enhancement of hearing using an amplification device. Seven bilateral fails in ABR were found, together with nine bilateral fails in TEOAE and four fails in FF screening at term age. Six preterm infants were later confirmed to have a significant permanent bilateral hearing loss, four of whom had also cerebral palsy. Bilateral failure in ABR screening predicted hearing loss with a sensitivity of 100% and a specificity of 98%, TEOAE with a sensitivity of 50% and a specificity of 84% and in the FF examination at the levels of 50% and 98%, respectively. Transient evoked otoacoustic emissions alone seem not to be so applicable to the neonatal screening of hearing in high-risk preterm infants as shown earlier in full-term infants, possibly because a hearing defect may be due to retrocochlear damage. Consequently, auditory brainstem response screening seems to be more suitable for very low birth weight preterm infants.

  9. Tumor Necrosis Factor-α– and Interleukin-1β–Dependent Matrix Metalloproteinase-3 Expression in Nucleus Pulposus Cells Requires Cooperative Signaling via Syndecan 4 and Mitogen-Activated Protein Kinase–NF-κB Axis

    PubMed Central

    Wang, Xin; Wang, Hua; Yang, Hao; Li, Jun; Cai, Qiqing; Shapiro, Irving M.; Risbud, Makarand V.

    2015-01-01

    Matrix metalloproteinase-3 (MMP-3) plays an important role in intervertebral disc degeneration, a ubiquitous condition closely linked to low back pain and disability. Elevated expression of syndecan 4, a cell surface heparan sulfate proteoglycan, actively controls disc matrix catabolism. However, the relationship between MMP-3 expression and syndecan 4 in the context of inflammatory disc disease has not been clearly defined. We investigated the mechanisms by which cytokines control MMP-3 expression in rat and human nucleus pulposus cells. Cytokine treatment increased MMP-3 expression and promoter activity. Stable silencing of syndecan 4 blocked cytokine-mediated MMP-3 expression; more important, syndecan 4 did not mediate its effects through NF-κB or mitogen-activated protein kinase (MAPK) pathways. However, treatment with MAPK and NF-κB inhibitors resulted in partial blocking of the inductive effect of cytokines on MMP-3 expression. Loss-of-function studies confirmed that NF-κB, p38α/β2/γ/δ, and extracellular signal–regulated kinase (ERK) 2, but not ERK1, contributed to cytokine-dependent induction of MMP3 promoter activity. Similarly, inhibitor treatments, lentiviral short hairpin-p65, and short hairpin-IκB kinase β significantly decreased cytokine-dependent up-regulation in MMP-3 expression. Finally, we show that transforming growth factor-β can block the up-regulation of MMP-3 induced by tumor necrosis factor (TNF)-α by counteracting the NF-κB pathway and syndecan 4 expression. Taken together, our results suggest that cooperative signaling through syndecan 4 and the TNF receptor 1–MAPK–NF-κB axis is required for TNF-α–dependent expression of MMP-3 in nucleus pulposus cells. Controlling these pathways may slow the progression of intervertebral disc degeneration and matrix catabolism. PMID:25063530

  10. Abnormal Neurological Responses in Young Adult Offspring Caused by Excess Omega-3 Fatty Acid (Fish Oil) Consumption by the Mother during Pregnancy and Lactation

    PubMed Central

    Church, M. W.; Jen, K-L. C.; Jackson, D. A.; Adams, B. R.; Hotra, J. W.

    2009-01-01

    Consuming omega-3 fatty acids (ω-3 FA) during pregnancy and lactation benefits fetal and infant brain development and might reduce the severity of preterm births by prolonging pregnancy. However, diets that are relatively rich in ω-3 FA can adversely affect fetal and infant development and the auditory brainstem response (ABR), a measure of brain development and sensory function. We previously examined the offspring of female rats fed excessive, adequate or deficient amounts of ω-3 FA during pregnancy and lactation. The 24-day-old offspring in the Excess group, compared to the Control group, had postnatal growth retardation and poor hearing acuity and prolonged neural transmission times as evidenced by the ABR. The Deficient group was intermediate. The current study followed these offspring to see if these poor outcomes persisted into young adulthood. Based on prior findings, we hypothesized that the Excess and Deficient offspring would “catch-up” to the Control offspring by young adulthood. Female Wistar rats received one of the three diet conditions from day 1 of pregnancy through lactation. The three diets were the Control ω-3 FA condition (ω-3/ω-6 ratio ~ 0.14), the Excess ω-3 FA condition (ω-3/ω-6 ratio ~ 14.0) and Deficient ω-3 FA condition (ω-3/ω-6 ratio ~ 0% ratio). The Control diet contained 7 % soybean oil; whereas the Deficient and Excess ω-3 FA diets contained 7% safflower oil and 7% fish oil, respectively. One male and female offspring per litter were ABR-tested as young adults using tone pip stimuli of 2, 4, 8 and 16 kHz. The postnatal growth retardation and prolonged neural transmission times in the Excess and Deficient pups had dissipated by young adulthood. In contrast, the Excess group had elevated ABR thresholds (hearing loss) at all tone pip frequencies in comparison to the Control and Deficient groups. The Deficient group had worse ABR thresholds than the Control group in response to the 8 kHz tone pips only. The Excess group also had ABR amplitude-intensity profiles suggestive of hyperacusis. These results are consistent with the Barker hypothesis concerning the fetal and neonatal origins of adult diseases. Thus, consuming diets that are excessively rich or deficient in ω-3 FA during pregnancy and lactation seems inadvisable because of risks for long-lasting adverse effects on brain development and sensory function. PMID:18834936

  11. Utility Rate Equations of Group Population Dynamics in Biological and Social Systems

    PubMed Central

    Yukalov, Vyacheslav I.; Yukalova, Elizaveta P.; Sornette, Didier

    2013-01-01

    We present a novel system of equations to describe the evolution of self-organized structured societies (biological or human) composed of several trait groups. The suggested approach is based on the combination of ideas employed in the theory of biological populations, system theory, and utility theory. The evolution equations are defined as utility rate equations, whose parameters are characterized by the utility of each group with respect to the society as a whole and by the mutual utilities of groups with respect to each other. We analyze in detail the cases of two groups (cooperators and defectors) and of three groups (cooperators, defectors, and regulators) and find that, in a self-organized society, neither defectors nor regulators can overpass the maximal fractions of about each. This is in agreement with the data for bee and ant colonies. The classification of societies by their distance from equilibrium is proposed. We apply the formalism to rank the countries according to the introduced metric quantifying their relative stability, which depends on the cost of defectors and regulators as well as their respective population fractions. We find a remarkable concordance with more standard economic ranking based, for instance, on GDP per capita. PMID:24386163

  12. Utility rate equations of group population dynamics in biological and social systems.

    PubMed

    Yukalov, Vyacheslav I; Yukalova, Elizaveta P; Sornette, Didier

    2013-01-01

    We present a novel system of equations to describe the evolution of self-organized structured societies (biological or human) composed of several trait groups. The suggested approach is based on the combination of ideas employed in the theory of biological populations, system theory, and utility theory. The evolution equations are defined as utility rate equations, whose parameters are characterized by the utility of each group with respect to the society as a whole and by the mutual utilities of groups with respect to each other. We analyze in detail the cases of two groups (cooperators and defectors) and of three groups (cooperators, defectors, and regulators) and find that, in a self-organized society, neither defectors nor regulators can overpass the maximal fractions of about [Formula: see text] each. This is in agreement with the data for bee and ant colonies. The classification of societies by their distance from equilibrium is proposed. We apply the formalism to rank the countries according to the introduced metric quantifying their relative stability, which depends on the cost of defectors and regulators as well as their respective population fractions. We find a remarkable concordance with more standard economic ranking based, for instance, on GDP per capita.

  13. 7 CFR 1150.119 - Cooperative association.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Cooperative association. 1150.119 Section 1150.119 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Order Definitions § 1150.119 Cooperative association. Cooperative association means any cooperative...

  14. Distributed adaptive neural network control for a class of heterogeneous nonlinear multi-agent systems subject to actuation failures

    NASA Astrophysics Data System (ADS)

    Cui, Bing; Zhao, Chunhui; Ma, Tiedong; Feng, Chi

    2017-02-01

    In this paper, the cooperative adaptive consensus tracking problem for heterogeneous nonlinear multi-agent systems on directed graph is addressed. Each follower is modelled as a general nonlinear system with the unknown and nonidentical nonlinear dynamics, disturbances and actuator failures. Cooperative fault tolerant neural network tracking controllers with online adaptive learning features are proposed to guarantee that all agents synchronise to the trajectory of one leader with bounded adjustable synchronisation errors. With the help of linear quadratic regulator-based optimal design, a graph-dependent Lyapunov proof provides error bounds that depend on the graph topology, one virtual matrix and some design parameters. Of particular interest is that if the control gain is selected appropriately, the proposed control scheme can be implemented in a unified framework no matter whether there are faults or not. Furthermore, the fault detection and isolation are not needed to implement. Finally, a simulation is given to verify the effectiveness of the proposed method.

  15. Dependency Links Can Hinder the Evolution of Cooperation in the Prisoner’s Dilemma Game on Lattices and Networks

    PubMed Central

    Wang, Xuwen; Nie, Sen; Wang, Binghong

    2015-01-01

    Networks with dependency links are more vulnerable when facing the attacks. Recent research also has demonstrated that the interdependent groups support the spreading of cooperation. We study the prisoner’s dilemma games on spatial networks with dependency links, in which a fraction of individual pairs is selected to depend on each other. The dependency individuals can gain an extra payoff whose value is between the payoff of mutual cooperation and the value of temptation to defect. Thus, this mechanism reflects that the dependency relation is stronger than the relation of ordinary mutual cooperation, but it is not large enough to cause the defection of the dependency pair. We show that the dependence of individuals hinders, promotes and never affects the cooperation on regular ring networks, square lattice, random and scale-free networks, respectively. The results for the square lattice and regular ring networks are demonstrated by the pair approximation. PMID:25798579

  16. Prophylaxis vs. on-demand treatment with BAY 81-8973, a full-length plasma protein-free recombinant factor VIII product: results from a randomized trial (LEOPOLD II)

    PubMed Central

    Kavakli, K; Yang, R; Rusen, L; Beckmann, H; Tseneklidou-Stoeter, D; Maas Enriquez, M

    2015-01-01

    Background BAY 81-8973 is a new full-length human recombinant factor VIII product manufactured with technologies to improve consistency in glycosylation and expression to optimize clinical performance. Objectives To demonstrate superiority of prophylaxis vs. on-demand therapy with BAY 81-8973 in patients with severe hemophilia A. Patients/Methods In this multinational, randomized, open-label crossover study (LEOPOLD II; ClinicalTrials.gov identifier: NCT01233258), males aged 12–65 years with severe hemophilia A were randomized to twice-weekly prophylaxis (20–30 IU kg−1), 3-times-weekly prophylaxis (30–40 IU kg−1), or on-demand treatment with BAY 81-8973. Potency labeling for BAY 81-8973 was based on the chromogenic substrate assay or adjusted to the one-stage assay. Primary efficacy endpoint was annualized number of all bleeds (ABR). Adverse events (AEs) and immunogenicity were also assessed. Results Eighty patients (on demand, n = 21; twice-weekly prophylaxis, n = 28; 3-times-weekly prophylaxis, n = 31) were treated and analyzed. Mean ± SD ABR was significantly lower with prophylaxis (twice-weekly, 5.7 ± 7.2; 3-times-weekly, 4.3 ± 6.5; combined, 4.9 ± 6.8) vs. on-demand treatment (57.7 ± 24.6; P < 0.0001, anova). Median ABR was reduced by 97% with prophylaxis (twice-weekly, 4.0; 3-times-weekly, 2.0; combined, 2.0) vs. on-demand treatment (60.0). Median ABR was higher with twice-weekly vs. 3-times-weekly prophylaxis during the first 6-month treatment period (4.1 vs. 2.0) but was comparable in the second 6-month period (1.1 vs. 2.0). Few patients reported treatment-related AEs (4%); no treatment-related serious AEs or inhibitors were reported. Conclusions Twice-weekly or 3-times-weekly prophylaxis with BAY 81-8973 reduced median ABR by 97% compared with on-demand therapy, confirming the superiority of prophylaxis. Treatment with BAY 81-8973 was well tolerated. PMID:25546368

  17. 7 CFR 989.12a - Cooperative bargaining association.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Cooperative bargaining association. 989.12a Section... PRODUCED FROM GRAPES GROWN IN CALIFORNIA Order Regulating Handling Definitions § 989.12a Cooperative bargaining association. Cooperative bargaining association means a nonprofit cooperative association of...

  18. Associations between prenatal and recent postnatal methylmercury exposure and auditory function at age 19 years in the Seychelles Child Development Study.

    PubMed

    Orlando, Mark S; Dziorny, Adam C; Harrington, Donald; Love, Tanzy; Shamlaye, Conrad F; Watson, Gene E; van Wijngaarden, Edwin; Davidson, Philip W; Myers, Gary J

    2014-01-01

    The aim of this study was to determine if prenatal or recent postnatal methylmercury (MeHg) exposure from consuming ocean fish and seafood is associated with auditory deficits in young adults. Some investigators have reported adverse associations while others have found no associations. Ocean fish is an important nutrient source for billions of people around the world. Consequently, determining if there is an adverse association with objective auditory measures is important in assessing whether a risk is present or not. The peripheral and central auditory function of 534 subjects in the Seychelles Child Development Study (SCDS) Main Cohort was examined at age of 19 years. The auditory test battery included standard pure-tone audiometry, tympanometry, auditory brainstem response (ABR) latencies, and both click-evoked and distortion product otoacoustic emissions (OAE). Associations with MeHg were evaluated with multiple linear regression models, adjusting for sex, recent postnatal MeHg exposure, and hearing loss. Bilateral hearing loss (defined as a mean pure-tone threshold of greater than 25 dB) was present in 1.1%of the subjects and was not associated with prenatal or recent postnatal MeHg exposure. As expected, absolute and interwave ABR latencies were shorter for women as compared to men, as the stimulus presentation rate decreased from 69.9 to 19.9 clicks/s and as the stimulus intensity increased from 60 to 80 dBnHL. Similarly, larger OAE amplitudes were elicited in women as compared to men and in the right ears as compared to the left. There was no association of prenatal MeHg exposure with hearing loss, ABR absolute and interwave latencies or OAE amplitudes. As recent postnatal MeHg increased, some associations were found with a few ABR absolute and interwave latencies and a few OAE amplitudes. However, the direction of these associations was inconsistent. As recent postnatal MeHg levels increased the wave I absolute latencies were shorter at 80 dBnHL for all three click rates, but the interwave I–V latency was longer for males for the 80 dBnHL 19 clicks/s and for the III–V interwave latencies for males and females for the dBnHL 69 clicks/s. Similarly, smaller OAE amplitudes were found at 1500, 2000, and 4000 Hz for males while larger OAE amplitudes were found for females at 1500 and 2000 Hz as the recent postnatal MeHg levels increased. No consistent associations were present in this study between prenatal MeHg exposure from consumption of oceanic fish and seafood during pregnancy and auditory functions at 19 years of age. Given the level of prenatal exposure to MeHg, the number of audiologic measures tested, and the presence of the expected sex, click rate, and level dependent findings, it seems unlikely that an association was present and not detected. As recent postnatal MeHg exposure increased, a few associations with ABR latencies and OAE amplitudes were found. The direction of these associations was inconsistent as some showed improved performance as MeHg exposure levels increased while others showed poorer performance. The presence of the inconsistent postnatal MeHg exposure findings are intriguing and deserve further clarification.

  19. [Therapeutic effect of insulin-like growth factor-1 injection into the inner ears through scala tympani fenestration on gentamicin-induced hearing loss in guinea pigs].

    PubMed

    Li, Yong-he; Chen, Hao; Guo, Meng-he

    2008-02-01

    To study the therapeutic effect of insulin-like growth factor-1 (IGF-1) injection into the inner ears through a scala tympani fenestration on sensorineural deafness in a guinea pig model of gentamicin-induced hearing loss. Twenty guinea pigs with gentamicin-induced hearing loss were randomized equally into IGF-1 group and control group. In both groups, scala tympani fenestration was performed for injection of IGF-1 (10 microl) or artificial perilymphatic fluid (10 microl). Auditory brainstem responses (ABR) test was performed before and 7 and 14 days after surgery, respectively, and the cochlea was removed by decollation of 3 guinea pigs from each group after ABR test for observing the changes in the hair cells using scanning electron microscope. Significant reduction in the ABR response threshold (RT) occurred in IGF-1 group 7 and 14 days after the surgery, and on day 14, ABR RT showed significant difference between IGF-1 group and the control group. Scanning electron microscopy revealed severer damages of the hair cells in the control group, and in the IGF-1 group, finger-like microvilli was detected on the surface of the damaged hair cells. IGF-1 injection in the inner ear through the scala tympani fenestration may ameliorate the damages of the auditory function and relieve sustained toxicity of gentamicin in guinea pigs possibly by protection and partial repair of the damaged cochlea hair cells as well as protection of the afferent nerves.

  20. Does systemic steroid deficiency affect inner ear functions?

    PubMed

    Dogan, Remzi; Merıc, Ayşenur; Gedık, Ozge; Tugrul, Selahattin; Eren, Sabri Baki; Ozturan, Orhan

    2015-01-01

    Today corticosteroids are employed for the treatment of various inner ear disorders. In this study we have investigated probable changes in hearing functions resulting from a deficiency of systemic steroid secretions. Twenty four healthy female rats were used in our study, allocated into three groups (medical adrenalectomy, medical adrenalectomy+dexamethasone, no treatment). Audiological evaluations were conducted at the beginning of the study and on days 7, 14 and 21. Blood samples were taken at the beginning and at the end of the study and blood corticosterone levels were determined. While there were no significant differences between the basal, 7th, 14th and 21st day DPOAE values of group 1, their ABR threshold values showed significant increases. In group 2, there were no significant differences between the basal, 7th, 14th and 21st day DPOAE values. ABR thresholds of group 2 showed significant increases on days 7 and 14 as compared to their basal values, but there were no significant differences between the 21st day and basal ABR threshold values. There were no significant differences between the basal cortisol levels of the three groups. The mean cortisol level of group 1 on day 21 was found to be significantly lower than those of groups 2 and 3. The results of the study demonstrated that there were no significant changes in DPOAE values with the cessation of cortisol secretion, while there was a progressive increase in ABR thresholds, which could be overcome with cortisone replacement. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. The Effect of Systemic Steroid on Hearing Preservation After Cochlear Implantation via Round Window Approach: A Guinea Pig Model.

    PubMed

    Chang, Mun Young; Rah, Yoon Chan; Choi, Jun Jae; Woo, Shin Wook; Hwang, Yu-Jung; Eastwood, Hayden; O'Leary, Stephen J; Lee, Jun Ho

    2017-08-01

    When administered perioperatively, systemic dexamethasone will reduce the hearing loss associated with cochlear implantation (CI) performed via the round window approach. The benefits of electroacoustic stimulation have led to interest in pharmacological interventions to preserve hearing after CI. Thirty guinea pigs were randomly divided into three experimental groups: a control group; a 3-day infusion group; and a 7-day infusion group. Dexamethasone was delivered via a mini-osmotic pump for either 3 or 7 days after CI via the round window. Pure tone-evoked auditory brainstem response (ABR) thresholds were monitored for a period of 12 weeks after CI. The cochleae were then collected for histology. At 4 and 12 weeks after CI, ABR threshold shifts were significantly reduced in both 7-day and 3-day infusion groups compared with the control group. Furthermore, the 7-day infusion group has significantly reduced ABR threshold shifts compared with the 3-day infusion group. The total tissue response, including fibrosis and ossification, was significantly reduced in the 7-day infusion group compared with the control group. On multiple regression the extent of fibrosis predicted hearing loss across most frequencies, while hair cell counts predicted ABR thresholds at 32 kHz. Hearing protection after systemic administration of steroids is more effective when continued for at least a week after CI. Similarly, this treatment approach was more effective in reducing the fibrosis that encapsulates the CI electrode. Reduced fibrosis seemed to be the most likely explanation for the hearing protection.

  2. Auditory function after application of ototopical vancomycin and mupirocin solutions in a murine model.

    PubMed

    Rutherford, Kimberley D; Kavanagh, Katherine; Parham, Kourosh

    2011-03-01

    To determine whether mupirocin (440 µg/mL) and vancomycin otic drops (25 mg/mL) show evidence of ototoxicity in CBA/J mice immediately following a 7-day course of daily intratympanic (IT) injections and 1 month following treatment. Nonrandomized controlled trial. Academic hospital laboratory. Twenty CBA/J mice. Mean auditory brainstem response (ABR) thresholds increased in all drug- and saline-treated ears immediately after 7 days of IT injections but returned to baseline for most stimulus frequencies by 30 days later. This finding appeared to be correlated with the presence and subsequent resolution of tympanic membrane (TM) perforations and granulation tissue at the injection sites. Mupirocin-treated ears showed no significant difference in ABR thresholds compared to saline-treated ears. No significant differences were noted between vancomycin- and saline-treated ears, but there was a significant interaction between testing day and stimulus frequency (P < .001). Further analysis revealed that ABR thresholds at 32 kHz remained significantly elevated in vancomycin-treated mice despite the resolution of TM perforations and granulation tissue 30 days after completion of IT injections (95% confidence interval, -13.5 to -5.5, P < .01). Although IT application of mupirocin solution (440 µg/mL) caused no significant change in the ABR thresholds in a murine model, vancomycin solution (25 mg/mL) resulted in high-frequency threshold elevations in both the ear directly injected and the contralateral ear. Mupirocin solution may be beneficial in managing otitis externa and media caused by resistant pathogens. Further studies of ototopical vancomycin are needed to define parameters governing its safe use.

  3. Toward a High-Stability Coherent Population Trapping Cs Vapor-Cell Atomic Clock Using Autobalanced Ramsey Spectroscopy

    NASA Astrophysics Data System (ADS)

    Abdel Hafiz, Moustafa; Coget, Grégoire; Petersen, Michael; Rocher, Cyrus; Guérandel, Stéphane; Zanon-Willette, Thomas; de Clercq, Emeric; Boudot, Rodolphe

    2018-06-01

    Vapor-cell atomic clocks are widely appreciated for their excellent short-term fractional frequency stability and their compactness. However, they are known to suffer on medium and long time scales from significant frequency instabilities, generally attributed to light-induced frequency-shift effects. In order to tackle this limitation, we investigate the application of the recently proposed autobalanced Ramsey (ABR) interrogation protocol onto a pulsed hot-vapor Cs vapor-cell clock based on coherent population trapping (CPT). We demonstrate that the ABR protocol, developed initially to probe the one-photon resonance of quantum optical clocks, can be successfully applied to a two-photon CPT resonance. The applied method, based on the alternation of two successive Ramsey-CPT sequences with unequal free-evolution times and the subsequent management of two interconnected phase and frequency servo loops, is found to allow a relevant reduction of the clock-frequency sensitivity to laser-power variations. This original ABR-CPT approach, combined with the implementation of advanced electronics laser-power stabilization systems, yields the demonstration of a CPT-based Cs vapor-cell clock with a short-term fractional frequency stability at the level of 3.1×10 -13τ-1 /2 , averaging down to the level of 6 ×10-15 at 2000-s integration time. These encouraging performances demonstrate that the use of the ABR interrogation protocol is a promising option towards the development of high-stability CPT-based frequency standards. Such clocks could be attractive candidates in numerous applications including next-generation satellite-based navigation systems, secure communications, instrumentation, or defense systems.

  4. Cooperative gene regulation by microRNA pairs and their identification using a computational workflow

    PubMed Central

    Schmitz, Ulf; Lai, Xin; Winter, Felix; Wolkenhauer, Olaf; Vera, Julio; Gupta, Shailendra K.

    2014-01-01

    MicroRNAs (miRNAs) are an integral part of gene regulation at the post-transcriptional level. Recently, it has been shown that pairs of miRNAs can repress the translation of a target mRNA in a cooperative manner, which leads to an enhanced effectiveness and specificity in target repression. However, it remains unclear which miRNA pairs can synergize and which genes are target of cooperative miRNA regulation. In this paper, we present a computational workflow for the prediction and analysis of cooperating miRNAs and their mutual target genes, which we refer to as RNA triplexes. The workflow integrates methods of miRNA target prediction; triplex structure analysis; molecular dynamics simulations and mathematical modeling for a reliable prediction of functional RNA triplexes and target repression efficiency. In a case study we analyzed the human genome and identified several thousand targets of cooperative gene regulation. Our results suggest that miRNA cooperativity is a frequent mechanism for an enhanced target repression by pairs of miRNAs facilitating distinctive and fine-tuned target gene expression patterns. Human RNA triplexes predicted and characterized in this study are organized in a web resource at www.sbi.uni-rostock.de/triplexrna/. PMID:24875477

  5. Identifying cooperative transcriptional regulations using protein–protein interactions

    PubMed Central

    Nagamine, Nobuyoshi; Kawada, Yuji; Sakakibara, Yasubumi

    2005-01-01

    Cooperative transcriptional activations among multiple transcription factors (TFs) are important to understand the mechanisms of complex transcriptional regulations in eukaryotes. Previous studies have attempted to find cooperative TFs based on gene expression data with gene expression profiles as a measure of similarity of gene regulations. In this paper, we use protein–protein interaction data to infer synergistic binding of cooperative TFs. Our fundamental idea is based on the assumption that genes contributing to a similar biological process are regulated under the same control mechanism. First, the protein–protein interaction networks are used to calculate the similarity of biological processes among genes. Second, we integrate this similarity and the chromatin immuno-precipitation data to identify cooperative TFs. Our computational experiments in yeast show that predictions made by our method have successfully identified eight pairs of cooperative TFs that have literature evidences but could not be identified by the previous method. Further, 12 new possible pairs have been inferred and we have examined the biological relevances for them. However, since a typical problem using protein–protein interaction data is that many false-positive data are contained, we propose a method combining various biological data to increase the prediction accuracy. PMID:16126847

  6. The Developmental Intestinal Regulator ELT-2 Controls p38-Dependent Immune Responses in Adult C. elegans

    PubMed Central

    Block, Dena H. S.; Twumasi-Boateng, Kwame; Kang, Hae Sung; Carlisle, Jolie A.; Hanganu, Alexandru; Lai, Ty Yu-Jen; Shapira, Michael

    2015-01-01

    GATA transcription factors play critical roles in cellular differentiation and development. However, their roles in mature tissues are less understood. In C. elegans larvae, the transcription factor ELT-2 regulates terminal differentiation of the intestine. It is also expressed in the adult intestine, where it was suggested to maintain intestinal structure and function, and where it was additionally shown to contribute to infection resistance. To study the function of elt-2 in adults we characterized elt-2-dependent gene expression following its knock-down specifically in adults. Microarray analysis identified two ELT-2-regulated gene subsets: one, enriched for hydrolytic enzymes, pointed at regulation of constitutive digestive functions as a dominant role of adult elt-2; the second was enriched for immune genes that are induced in response to Pseudomonas aeruginosa infection. Focusing on the latter, we used genetic analyses coupled to survival assays and quantitative RT-PCR to interrogate the mechanism(s) through which elt-2 contributes to immunity. We show that elt-2 controls p38-dependent gene induction, cooperating with two p38-activated transcription factors, ATF-7 and SKN-1. This demonstrates a mechanism through which the constitutively nuclear elt-2 can impact induced responses, and play a dominant role in C. elegans immunity. PMID:26016853

  7. Torque measurements reveal sequence-specific cooperative transitions in supercoiled DNA

    PubMed Central

    Oberstrass, Florian C.; Fernandes, Louis E.; Bryant, Zev

    2012-01-01

    B-DNA becomes unstable under superhelical stress and is able to adopt a wide range of alternative conformations including strand-separated DNA and Z-DNA. Localized sequence-dependent structural transitions are important for the regulation of biological processes such as DNA replication and transcription. To directly probe the effect of sequence on structural transitions driven by torque, we have measured the torsional response of a panel of DNA sequences using single molecule assays that employ nanosphere rotational probes to achieve high torque resolution. The responses of Z-forming d(pGpC)n sequences match our predictions based on a theoretical treatment of cooperative transitions in helical polymers. “Bubble” templates containing 50–100 bp mismatch regions show cooperative structural transitions similar to B-DNA, although less torque is required to disrupt strand–strand interactions. Our mechanical measurements, including direct characterization of the torsional rigidity of strand-separated DNA, establish a framework for quantitative predictions of the complex torsional response of arbitrary sequences in their biological context. PMID:22474350

  8. Audiological characteristics of infants with abnormal transient evoked otoacoustic emission and normal auditory brainstem response.

    PubMed

    Huang, Lihui; Han, Demin; Guo, Ying; Liu, Sha; Cui, Xiaoyan; Mo, Lingyan; Qi, Beier; Cai, Zhenghua; Liu, Hui; En, Hui; Guo, Liansheng

    2008-10-01

    Audiological characteristics were investigated in 81 ears of 53 infants with abnormal transient evoked otoacoustic emission (TEOAE) and normal auditory brainstem response (ABR). The relationship between ABR and other hearing testing methods, including 40Hz auditory event-related potential (40Hz-AERP), auditory steady state response (ASSR), distortion product otoacoustic emission (DPOAE), tympanometry, and acoustic reflex, was analyzed. Of the 81 ears, 18 ears (22.2%) were normal, while 63 ears (77.8%) were abnormal according to the tests. Testing of the 40 Hz AERP (36 ears) and ASSR (45 ears) revealed that 14 ears (38.9%) and 27 ears (60.0%) were abnormal, respectively. Testing of DPOAE in 68 ears revealed that 50 ears (73.5%) were abnormal. Testing of tympanometry in 50 ears and acoustic reflex in 47 ears revealed that 9 ears (18%) and 27 ears (57.4%) were abnormal, respectively. The present data suggests that the hearing of infants cannot be sufficiently evaluated with ABR only and that it must be evaluated with integrative audiological testing methods.

  9. Biomethanation of vegetable market waste in an anaerobic baffled reactor: Effect of effluent recirculation and carbon mass balance analysis.

    PubMed

    Gulhane, Madhuri; Khardenavis, Anshuman A; Karia, Sneha; Pandit, Prabhakar; Kanade, Gajanan S; Lokhande, Satish; Vaidya, Atul N; Purohit, Hemant J

    2016-09-01

    In the present study, feasibility of biomethanation of vegetable market waste in a 4-chambered anaerobic baffled reactor (ABR) was investigated at 30d hydraulic retention time and organic loading rate of 0.5gVS/L/d for one year. Indicators of process stability viz., butyrate/acetate and propionate/acetate ratios were consistent with phase separation in the different chambers, which remained unaltered even during recirculation of effluent. Chemical oxygen demand (COD) and volatile solids (VS) removal efficiencies were observed to be consistently high (above 90%). Corresponding biogas and methane yields of 0.7-0.8L/g VS added/d and 0.42-52L/g VS added/d respectively were among the highest reported in case of AD of vegetable waste in an ABR. Process efficiency of the ABR for vegetable waste methanation, which is indicated by carbon recovery factor showed that, nearly 96.7% of the input carbon considered for mass balance was accounted for in the product. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Human inferior colliculus activity relates to individual differences in spoken language learning

    PubMed Central

    Chandrasekaran, Bharath; Kraus, Nina

    2012-01-01

    A challenge to learning words of a foreign language is encoding nonnative phonemes, a process typically attributed to cortical circuitry. Using multimodal imaging methods [functional magnetic resonance imaging-adaptation (fMRI-A) and auditory brain stem responses (ABR)], we examined the extent to which pretraining pitch encoding in the inferior colliculus (IC), a primary midbrain structure, related to individual variability in learning to successfully use nonnative pitch patterns to distinguish words in American English-speaking adults. fMRI-A indexed the efficiency of pitch representation localized to the IC, whereas ABR quantified midbrain pitch-related activity with millisecond precision. In line with neural “sharpening” models, we found that efficient IC pitch pattern representation (indexed by fMRI) related to superior neural representation of pitch patterns (indexed by ABR), and consequently more successful word learning following sound-to-meaning training. Our results establish a critical role for the IC in speech-sound representation, consistent with the established role for the IC in the representation of communication signals in other animal models. PMID:22131377

  11. Investigation of Anthrax Cases in North-East China, 2010-2014.

    PubMed

    Zhou, Wei; Sun, Yang; Zhu, Lingwei; Zhou, Bo; Liu, Jun; Ji, Xue; Wang, Xiaofeng; Wang, Nan; Gu, Guibo; Feng, Shuzhang; Qian, Jun; Guo, Xuejun

    2015-01-01

    We determined the genotypes of seven Bacillus anthracis strains that were recovered from nine anthrax outbreaks in North-East China from 2010 to 2014, and two approved vaccine strains that are currently in use in China. The causes of these cases were partly due to local farmers being unaware of the presence of anthrax, and butchers with open wounds having direct contact with anthrax-contaminated meat products. The genotype of five of the seven recovered strains was A.Br.001/002 sub-lineage, which was concordant with previously published research. The remaining two cases belongs to the A.Br.Ames sub-lineage. Both of these strains displayed an identical SNR pattern, which was the first time that this genotype was identified in North-East China. Strengthening education in remote villages of rural China is an important activity aimed at fostering attempts to prevent and control anthrax. The genotype of the vaccine strain Anthrax Spore Vaccine No.II was A.Br.008/009 and A.Br.001/002 for the vaccine strain Anthrax Spore Vaccine Non-capsulated. Further studies of their characteristics are clearly warranted.

  12. Cis-regulatory element based targeted gene finding: genome-wide identification of abscisic acid- and abiotic stress-responsive genes in Arabidopsis thaliana.

    PubMed

    Zhang, Weixiong; Ruan, Jianhua; Ho, Tuan-Hua David; You, Youngsook; Yu, Taotao; Quatrano, Ralph S

    2005-07-15

    A fundamental problem of computational genomics is identifying the genes that respond to certain endogenous cues and environmental stimuli. This problem can be referred to as targeted gene finding. Since gene regulation is mainly determined by the binding of transcription factors and cis-regulatory DNA sequences, most existing gene annotation methods, which exploit the conservation of open reading frames, are not effective in finding target genes. A viable approach to targeted gene finding is to exploit the cis-regulatory elements that are known to be responsible for the transcription of target genes. Given such cis-elements, putative target genes whose promoters contain the elements can be identified. As a case study, we apply the above approach to predict the genes in model plant Arabidopsis thaliana which are inducible by a phytohormone, abscisic acid (ABA), and abiotic stress, such as drought, cold and salinity. We first construct and analyze two ABA specific cis-elements, ABA-responsive element (ABRE) and its coupling element (CE), in A.thaliana, based on their conservation in rice and other cereal plants. We then use the ABRE-CE module to identify putative ABA-responsive genes in A.thaliana. Based on RT-PCR verification and the results from literature, this method has an accuracy rate of 67.5% for the top 40 predictions. The cis-element based targeted gene finding approach is expected to be widely applicable since a large number of cis-elements in many species are available.

  13. Analysis of an osmotically regulated pathogenesis-related osmotin gene promoter.

    PubMed

    Raghothama, K G; Liu, D; Nelson, D E; Hasegawa, P M; Bressan, R A

    1993-12-01

    Osmotin is a small (24 kDa), basic, pathogenesis-related protein, that accumulates during adaptation of tobacco (Nicotiana tabacum) cells to osmotic stress. There are more than 10 inducers that activate the osmotin gene in various plant tissues. The osmotin promoter contains several sequences bearing a high degree of similarity to ABRE, as-1 and E-8 cis element sequences. Gel retardation studies indicated the presence of at least two regions in the osmotin promoter that show specific interactions with nuclear factors isolated from cultured cells or leaves. The abundance of these binding factors increased in response to salt, ABA and ethylene. Nuclear factors protected a 35 bp sequence of the promoter from DNase I digestion. Different 5' deletions of the osmotin promoter cloned into a promoter-less GUSNOS plasmid (pBI 201) were used in transient expression studies with a Biolistic gun. The transient expression studies revealed the presence of three distinct regions in the osmotin promoter. The promoter sequence from -108 to -248 bp is absolutely required for reporter gene activity, followed by a long stretch (up to -1052) of enhancer-like sequence and then a sequence upstream of -1052, which appears to contain negative elements. The responses to ABA, ethylene, salt, desiccation and wounding appear to be associated with the -248 bp sequence of the promoter. This region also contains a putative ABRE (CACTGTG) core element. Activation of the osmotin gene by various inducers is discussed in view of antifungal activity of the osmotin protein.

  14. Dynamic Evolution of 2D Layers Within Perovskite Nanocrystals via Salt Pair Extraction and Reinsertion

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

    Wheeler, Lance M; Anderson, Nicholas C; Bliss, Taylor

    Metal halide perovskite (MHP) semiconductors exhibit unprecedented optoelectronic properties coupled with low formation energies that enable scalable, cost-efficient solution processing. The low formation energies additionally facilitate dynamic transformation of the chemical composition and crystal structure of the MHP material. In this work, we show that CsBr salt is selectively extracted from CsPbBr3 nanocrystals (NCs) to yield PbBr2 NCs. The PbBr2 NCs are then exposed to different glacial acetic acid ABr salt solutions to generate a variety of emissive compounds with the generic structure A'2An-1PbnBr3n-1X'2, where A = cesium (Cs+), methylammonium (MA+), formamidinium (FA+); A' = A or H+; X' =more » Br- or acetate (CH3COO-); and n is the number of lead halide layers, where n = 1, 2, 3, ...8. We systematically vary the ratios of PbBr2/ABr/CH3COOH and show that certain ratios result in isolable single-phase APbBr3 NCs - an effective A-site cation exchange from the parent CsPbBr3 NCs. Importantly, time-resolved photoluminescence (PL) spectroscopy shows the dynamic evolution of many additional species as evidenced by blue-shifted emission peaks from 2.85-2.49 eV for MA+-based structures. We assign these species to n = 1, 2, 3, 4, and 5 quasi-two-dimensional network (2DN) sheets, in which CH3COO- anions and Br- anions compete for the c-axis X' sites separating haloplumbate(II) layers within the A'2An-1PbnBr3n-1X'2 NCs. Finally, we demonstrate the degree of CH3COO- incorporation, and thus the 2DN layer thickness and PL energy, is controlled in the early reaction times by kinetic factors. After a longer time (3 h), thermodynamic forces dictated by Le Chatelier's principle tune the structure in A'2An-1PbnBr3n-1X'2 NCs from exclusively n = 1 to n = 8 depending on the PbBr2/ABr/CH3COOH ratio.« less

  15. 7 CFR 3430.1 - Applicability of regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION... evaluation, award, and post-award administration of, Cooperative State Research, Education, and Extension... 3016 (State, local, and tribal governments), 3019 (institutions of higher education, hospitals, and...

  16. Cohesion-decohesion asymmetry in geckos

    NASA Astrophysics Data System (ADS)

    Puglisi, G.; Truskinovsky, L.

    2013-03-01

    Lizards and insects can strongly attach to walls and then detach applying negligible additional forces. We propose a simple mechanical model of this phenomenon which implies active muscle control. We show that the detachment force may depend not only on the properties of the adhesive units, but also on the elastic interaction among these units. By regulating the scale of such cooperative interaction, the organism can actively switch between two modes of adhesion: delocalized (pull off) and localized (peeling).

  17. 78 FR 9775 - Cooper Tire & Rubber Company, Receipt of Petition for Decision of Inconsequential Noncompliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-11

    ...: Cooper Tire & Rubber Company (Cooper),\\1\\ has determined that certain Cooper brand tires manufactured... brand standard load tires manufactured in Mexico by Cooper's affiliate, Corporaci[oacute]n de Occidente... Docket Management System (FDMS) Web site at http://www.regulations.gov/ . Follow the online instructions...

  18. Juxtaposed Polycomb complexes co-regulate vertebral identity.

    PubMed

    Kim, Se Young; Paylor, Suzanne W; Magnuson, Terry; Schumacher, Armin

    2006-12-01

    Best known as epigenetic repressors of developmental Hox gene transcription, Polycomb complexes alter chromatin structure by means of post-translational modification of histone tails. Depending on the cellular context, Polycomb complexes of diverse composition and function exhibit cooperative interaction or hierarchical interdependency at target loci. The present study interrogated the genetic, biochemical and molecular interaction of BMI1 and EED, pivotal constituents of heterologous Polycomb complexes, in the regulation of vertebral identity during mouse development. Despite a significant overlap in dosage-sensitive homeotic phenotypes and co-repression of a similar set of Hox genes, genetic analysis implicated eed and Bmi1 in parallel pathways, which converge at the level of Hox gene regulation. Whereas EED and BMI1 formed separate biochemical entities with EzH2 and Ring1B, respectively, in mid-gestation embryos, YY1 engaged in both Polycomb complexes. Strikingly, methylated lysine 27 of histone H3 (H3-K27), a mediator of Polycomb complex recruitment to target genes, stably associated with the EED complex during the maintenance phase of Hox gene repression. Juxtaposed EED and BMI1 complexes, along with YY1 and methylated H3-K27, were detected in upstream regulatory regions of Hoxc8 and Hoxa5. The combined data suggest a model wherein epigenetic and genetic elements cooperatively recruit and retain juxtaposed Polycomb complexes in mammalian Hox gene clusters toward co-regulation of vertebral identity.

  19. OsSLI1, a homeodomain containing transcription activator, involves abscisic acid related stress response in rice (Oryza sativa L.).

    PubMed

    Huang, Xi; Duan, Min; Liao, Jiakai; Yuan, Xi; Chen, Hui; Feng, Jiejie; Huang, Ji; Zhang, Hong-Sheng

    2014-01-01

    Homeodomain-leucine zipper type I (HD-Zip I) proteins are involved in the regulation of plant development and response to environmental stresses. In this study, OsSLI1 (Oryza sativa stress largely induced 1), encoding a member of the HD-Zip I subfamily, was isolated from rice. The expression of OsSLI1 was dramatically induced by multiple abiotic stresses and exogenous abscisic acid (ABA). In silico sequence analysis discovered several cis-acting elements including multiple ABREs (ABA-responsive element binding factors) in the upstream promoter region of OsSLI1. The OsSLI1-GFP fusion protein was localized in the nucleus of rice protoplast cells and the transcriptional activity of OsSLI1 was confirmed by the yeast hybrid system. Further, it was found that OsSLI1 expression was enhanced in an ABI5-Like1 (ABL1) deficiency rice mutant abl1 under stress conditions, suggesting that ABL1 probably negatively regulates OsSLI1 gene expression. Moreover, it was found that OsSLI1 was regulated in panicle development. Taken together, OsSLI1 may be a transcriptional activator regulating stress-responsive gene expression and panicle development in rice.

  20. Cooperative binding mitigates the high-dose hook effect.

    PubMed

    Roy, Ranjita Dutta; Rosenmund, Christian; Stefan, Melanie I

    2017-08-14

    The high-dose hook effect (also called prozone effect) refers to the observation that if a multivalent protein acts as a linker between two parts of a protein complex, then increasing the amount of linker protein in the mixture does not always increase the amount of fully formed complex. On the contrary, at a high enough concentration range the amount of fully formed complex actually decreases. It has been observed that allosterically regulated proteins seem less susceptible to this effect. The aim of this study was two-fold: First, to investigate the mathematical basis of how allostery mitigates the prozone effect. And second, to explore the consequences of allostery and the high-dose hook effect using the example of calmodulin, a calcium-sensing protein that regulates the switch between long-term potentiation and long-term depression in neurons. We use a combinatorial model of a "perfect linker protein" (with infinite binding affinity) to mathematically describe the hook effect and its behaviour under allosteric conditions. We show that allosteric regulation does indeed mitigate the high-dose hook effect. We then turn to calmodulin as a real-life example of an allosteric protein. Using kinetic simulations, we show that calmodulin is indeed subject to a hook effect. We also show that this effect is stronger in the presence of the allosteric activator Ca 2+ /calmodulin-dependent kinase II (CaMKII), because it reduces the overall cooperativity of the calcium-calmodulin system. It follows that, surprisingly, there are conditions where increased amounts of allosteric activator actually decrease the activity of a protein. We show that cooperative binding can indeed act as a protective mechanism against the hook effect. This will have implications in vivo where the extent of cooperativity of a protein can be modulated, for instance, by allosteric activators or inhibitors. This can result in counterintuitive effects of decreased activity with increased concentrations of both the allosteric protein itself and its allosteric activators.

  1. In vivo collective cell migration requires an LPAR2-dependent increase in tissue fluidity.

    PubMed

    Kuriyama, Sei; Theveneau, Eric; Benedetto, Alexandre; Parsons, Maddy; Tanaka, Masamitsu; Charras, Guillaume; Kabla, Alexandre; Mayor, Roberto

    2014-07-07

    Collective cell migration (CCM) and epithelial-mesenchymal transition (EMT) are common to cancer and morphogenesis, and are often considered to be mutually exclusive in spite of the fact that many cancer and embryonic cells that have gone through EMT still cooperate to migrate collectively. Here we use neural crest (NC) cells to address the question of how cells that have down-regulated cell-cell adhesions can migrate collectively. NC cell dissociation relies on a qualitative and quantitative change of the cadherin repertoire. We found that the level of cell-cell adhesion is precisely regulated by internalization of N-cadherin downstream of lysophosphatidic acid (LPA) receptor 2. Rather than promoting the generation of single, fully mesenchymal cells, this reduction of membrane N-cadherin only triggers a partial mesenchymal phenotype. This intermediate phenotype is characterized by an increase in tissue fluidity akin to a solid-like-to-fluid-like transition. This change of plasticity allows cells to migrate under physical constraints without abolishing cell cooperation required for collectiveness. © 2014 Kuriyama et al.

  2. Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response.

    PubMed

    Ciccia, Alberto; Huang, Jen-Wei; Izhar, Lior; Sowa, Mathew E; Harper, J Wade; Elledge, Stephen J

    2014-12-30

    The signal transduction pathway of the DNA damage response (DDR) is activated to maintain genomic integrity following DNA damage. The DDR promotes genomic integrity by regulating a large network of cellular activities that range from DNA replication and repair to transcription, RNA splicing, and metabolism. In this study we define an interaction between the DDR factor NBS1 and TCOF1, a nucleolar protein that regulates ribosomal DNA (rDNA) transcription and is mutated in Treacher Collins syndrome. We show that NBS1 relocalizes to nucleoli after DNA damage in a manner dependent on TCOF1 and on casein kinase II and ATM, which are known to modify TCOF1 by phosphorylation. Moreover, we identify a putative ATM phosphorylation site that is required for NBS1 relocalization to nucleoli in response to DNA damage. Last, we report that TCOF1 promotes cellular resistance to DNA damaging agents. Collectively, our findings identify TCOF1 as a DDR factor that could cooperate with ATM and NBS1 to suppress inappropriate rDNA transcription and maintain genomic integrity after DNA damage.

  3. Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response

    PubMed Central

    Ciccia, Alberto; Huang, Jen-Wei; Izhar, Lior; Sowa, Mathew E.; Harper, J. Wade; Elledge, Stephen J.

    2014-01-01

    The signal transduction pathway of the DNA damage response (DDR) is activated to maintain genomic integrity following DNA damage. The DDR promotes genomic integrity by regulating a large network of cellular activities that range from DNA replication and repair to transcription, RNA splicing, and metabolism. In this study we define an interaction between the DDR factor NBS1 and TCOF1, a nucleolar protein that regulates ribosomal DNA (rDNA) transcription and is mutated in Treacher Collins syndrome. We show that NBS1 relocalizes to nucleoli after DNA damage in a manner dependent on TCOF1 and on casein kinase II and ATM, which are known to modify TCOF1 by phosphorylation. Moreover, we identify a putative ATM phosphorylation site that is required for NBS1 relocalization to nucleoli in response to DNA damage. Last, we report that TCOF1 promotes cellular resistance to DNA damaging agents. Collectively, our findings identify TCOF1 as a DDR factor that could cooperate with ATM and NBS1 to suppress inappropriate rDNA transcription and maintain genomic integrity after DNA damage. PMID:25512513

  4. Physical and functional connection between auxilin and dynamin during endocytosis

    PubMed Central

    Sever, Sanja; Skoch, Jesse; Newmyer, Sherri; Ramachandran, Rajesh; Ko, David; McKee, Mary; Bouley, Richard; Ausiello, Dennis; Hyman, Bradley T; Bacskai, Brian J

    2006-01-01

    During clathrin-mediated endocytosis, the GTPase dynamin promotes formation of clathrin-coated vesicles, but its mode of action is unresolved. We provide evidence that a switch in three functional states of dynamin (dimers, tetramers, rings/spirals) coordinates its GTPase cycle. Dimers exhibit negative cooperativity whereas tetramers exhibit positive cooperativity with respect to GTP. Our study identifies tetramers as the kinetically most stable GTP-bound conformation of dynamin, which is required to promote further assembly into higher order structures such as rings or spirals. In addition, using fluorescence lifetime imaging microscopy, we show that interactions between dynamin and auxilin in cells are GTP-, endocytosis- and tetramer-dependent. Furthermore, we show that the cochaperone activity of auxilin is required for constriction of clathrin-coated pits, the same early step in endocytosis known to be regulated by the lifetime of dynamin:GTP. Together, our findings support the model that the GTP-bound conformation of dynamin tetramers stimulates formation of constricted coated pits at the plasma membrane by regulating the chaperone activity of hsc70/auxilin. PMID:16946707

  5. Preventive Effect of CPP-ACPF Paste and Fluoride Toothpastes Against Erosion and Erosion Plus Abrasion 
In Vitro - A 3D Profilometric Analysis.

    PubMed

    Soares, Genaina Guimarães; Magalhães, Pâmela Amorim; Fonseca, Ana Beatriz Monteiro; Tostes, Monica Almeida; Silva, Eduardo Moreira da; Coutinho, Thereza Christina Lopes

    To evaluate the effect of CPP-ACPF paste and fluoride toothpastes on enamel subjected to erosion and erosion plus abrasion in vitro. A total of 220 human enamel blocks were divided into eleven groups (n = 20): CPP-ACPF paste (MPP), potassium nitrate/sodium fluoride toothpaste (PE), sodium fluoride toothpaste (FD), fluoride-free toothpaste (SO) and control (erosion only with no paste or toothpastes; CO) according to the experimental design: erosion or erosion plus abrasion immediately after erosion (ERO+I-ABR) or 30 min after erosion (ERO+30min-ABR). For 5 days, the specimens were subjected to: (1) erosive challenge (EC) (cola drink, 4 x 5 min/day), topical application of the undiluted paste or diluted toothpastes (1:2 w/w) (4 x 1 min/ day) plus 1 h in artificial saliva (AS) between cycles and overnight; or (2) EC plus abrasion (4 x /60 s/day) performed with the diluted toothpastes (no MMP) plus 1 h in AS between cycles and overnight. Erosion depth was quantified through a 3D profilometer. Data were analysed using Kruskal-Wallis, Mann-Whitney and Wilcoxon tests (p = 0.05). CPP-ACPF paste and NaF toothpaste showed lowest enamel wear among groups and reduced tissue loss by 89% in erosion challenge. Abrasion led to higher enamel wear than erosion only (p = 0.030). ERO+30min-ABR had no protective effect when compared to ERO+I-ABR (p > 0.05). A high frequency of CPP-ACPF paste application (4x daily) is effective in reducing the effects of erosion. A waiting period before performing toothbrushing does not protect enamel against erosion regardless the composition of the toothpastes.

  6. The Corticofugal Effects of Auditory Cortex Microstimulation on Auditory Nerve and Superior Olivary Complex Responses Are Mediated via Alpha-9 Nicotinic Receptor Subunit

    PubMed Central

    Aedo, Cristian; Terreros, Gonzalo; León, Alex; Delano, Paul H.

    2016-01-01

    Background and Objective The auditory efferent system is a complex network of descending pathways, which mainly originate in the primary auditory cortex and are directed to several auditory subcortical nuclei. These descending pathways are connected to olivocochlear neurons, which in turn make synapses with auditory nerve neurons and outer hair cells (OHC) of the cochlea. The olivocochlear function can be studied using contralateral acoustic stimulation, which suppresses auditory nerve and cochlear responses. In the present work, we tested the proposal that the corticofugal effects that modulate the strength of the olivocochlear reflex on auditory nerve responses are produced through cholinergic synapses between medial olivocochlear (MOC) neurons and OHCs via alpha-9/10 nicotinic receptors. Methods We used wild type (WT) and alpha-9 nicotinic receptor knock-out (KO) mice, which lack cholinergic transmission between MOC neurons and OHC, to record auditory cortex evoked potentials and to evaluate the consequences of auditory cortex electrical microstimulation in the effects produced by contralateral acoustic stimulation on auditory brainstem responses (ABR). Results Auditory cortex evoked potentials at 15 kHz were similar in WT and KO mice. We found that auditory cortex microstimulation produces an enhancement of contralateral noise suppression of ABR waves I and III in WT mice but not in KO mice. On the other hand, corticofugal modulations of wave V amplitudes were significant in both genotypes. Conclusion These findings show that the corticofugal modulation of contralateral acoustic suppressions of auditory nerve (ABR wave I) and superior olivary complex (ABR wave III) responses are mediated through MOC synapses. PMID:27195498

  7. Cortical and subcortical processing of short duration speech stimuli in trained rock musicians: a pilot study.

    PubMed

    Kumar, Prawin; Anil, Sam Publius; Grover, Vibhu; Sanju, Himanshu Kumar; Sinha, Sachchidanand

    2017-02-01

    Most trained musicians are actively involved in rigorous practice from several years to achieve a high level of proficiency. Therefore, musicians are best group to research changes or modification in brain structures and functions across several information processing systems. This study aimed to investigate cortical and subcortical processing of short duration speech stimuli in trained rock musicians and non-musicians. Two groups of participant (experimental and control groups) in the age range of 18-25 years were selected for the study. Experimental group includes 15 rock musicians who had minimum professional training of 5 years of rock music, and each member had to be a regular performer of rock music for at least 15 h a week. Further age-matched 15 participants who were not having any formal training of any music served as non-musicians, in the control group. The speech-evoked ABR (S-ABR) and speech-evoked ALLR (S-LLR) with short duration speech 'synthetic /da/' was elicited in both groups. Different measures were analyzed for S-ABR and S-LLR. For S-ABR, MANOVA revealed significant main effect of groups on latencies of wave V, wave A, and amplitude of wave V/A slope. Similarly, Kruskal-Wallis test showed significantly higher F 0 amplitude in rock musicians compared with non-musicians. For S-LLR, MANOVA showed statistically significant differences observed for latencies of wave P2 and N2 and amplitude measures of P2-N2 amplitude. This study indicated better neural processing of short duration speech stimuli at subcortical as well as cortical level among rock musicians when compared with non-musicians.

  8. Auditory agnosia as a clinical symptom of childhood adrenoleukodystrophy.

    PubMed

    Furushima, Wakana; Kaga, Makiko; Nakamura, Masako; Gunji, Atsuko; Inagaki, Masumi

    2015-08-01

    To investigate detailed auditory features in patients with auditory impairment as the first clinical symptoms of childhood adrenoleukodystrophy (CSALD). Three patients who had hearing difficulty as the first clinical signs and/or symptoms of ALD. Precise examination of the clinical characteristics of hearing and auditory function was performed, including assessments of pure tone audiometry, verbal sound discrimination, otoacoustic emission (OAE), and auditory brainstem response (ABR), as well as an environmental sound discrimination test, a sound lateralization test, and a dichotic listening test (DLT). The auditory pathway was evaluated by MRI in each patient. Poor response to calling was detected in all patients. Two patients were not aware of their hearing difficulty, and had been diagnosed with normal hearing by otolaryngologists at first. Pure-tone audiometry disclosed normal hearing in all patients. All patients showed a normal wave V ABR threshold. Three patients showed obvious difficulty in discriminating verbal sounds, environmental sounds, and sound lateralization and strong left-ear suppression in a dichotic listening test. However, once they discriminated verbal sounds, they correctly understood the meaning. Two patients showed elongation of the I-V and III-V interwave intervals in ABR, but one showed no abnormality. MRIs of these three patients revealed signal changes in auditory radiation including in other subcortical areas. The hearing features of these subjects were diagnosed as auditory agnosia and not aphasia. It should be emphasized that when patients are suspected to have hearing impairment but have no abnormalities in pure tone audiometry and/or ABR, this should not be diagnosed immediately as psychogenic response or pathomimesis, but auditory agnosia must also be considered. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  9. Sex differences in distortion product otoacoustic emissions as a function of age in CBA mice.

    PubMed

    Guimaraes, Patricia; Zhu, Xiaoxia; Cannon, Trinitia; Kim, SungHee; Frisina, Robert D

    2004-06-01

    Age-related hearing loss--presbycusis--is the number one communication problem of the aged. A major contributor to presbycusis is the progressive degeneration of cochlear outer hair cells (OHCs). Distortion product otoacoustic emissions (DPOAEs) are effective in vivo, physiological measures of hearing, assessing the health and functioning of the OHCs in mammals. We and others have previously demonstrated that DPOAE amplitudes decline with age in humans and mice. The present study's objective was to measure age-related declines in the OHCs in CBA mice (slow, progressive age-related hearing loss) by comparing DPOAEs and auditory brainstem responses (ABRs) generated from females and males. Young adult (2.1-2.9 months) and middle-aged CBA (14.0-16.4 months) mice were tested, as well as old CBAs (24.3-29.0 months). DPOAE-grams were obtained with L1 = 65 and L2 = 50 dB SPL, f1/f2 = 1.25, using eight points per octave covering a frequency range from 5.6 to 44.8 kHz (geometric mean frequency). ABRs ranged from 3 to 48 kHz. Analyses revealed that DPOAE levels decreased with age for middle-aged and old male CBAs, but for female CBAs, declines did not occur until old age - after menopause. In contrast, ABR amplitudes for female and male young adult and middle-aged CBAs were the same. Female ABR thresholds were lower than males for old CBAs. In conclusion, we discovered that pre-menopausal CBA female mice have healthier OHCs relative to middle-aged males, but much of this relative advantage is lost post-menopause. Understanding sex differences in age-related sensory disorders will be quite helpful for the goals of preventing, slowing or curing sensory problems in old age for both women and men.

  10. Prolonged noise exposure-induced auditory threshold shifts in rats

    PubMed Central

    Chen, Guang-Di; Decker, Brandon; Muthaiah, Vijaya Prakash Krishnan; Sheppard, Adam; Salvi, Richard

    2014-01-01

    Noise-induced hearing loss (NIHL) initially increases with exposure duration, but eventually reaches an asymptotic threshold shift (ATS) once the exposure duration exceeds 18-24 h. Equations for predicting the ATS have been developed for several species, but not for rats, even though this species is extensively used in noise exposure research. To fill this void, we exposed rats to narrowband noise (NBN, 16-20 kHz) for 5 weeks starting at 80 dB SPL in the first week and then increasing the level by 6 dB per week to a final level of 104 dB SPL. Auditory brainstem responses (ABR) were recorded before, during, and following the exposure to determine the amount of hearing loss. The noise induced threshold shift to continuous long-term exposure, defined as compound threshold shift (CTS), within and above 16-20 kHz increased with noise level at the rate of 1.82 dB threshold shift per dB of noise level (NL) above a critical level (C) of 77.2 dB SPL i.e. CTS = 1.82(NL-77.2). The normalized amplitude of the largest ABR peak measured at 100 dB SPL decreased at the rate of 3.1% per dB of NL above the critical level of 76.9 dB SPL, i.e., %ABR Reduction = 3.1%(NL-76.9). ABR thresholds measured >30 days post-exposure only partially recovered resulting in a permanent threshold shift of 30-40 dB along with severe hair cell loss in the basal, high-frequency region of the cochlea. In the rat, CTS increases with noise level with a slope similar to humans and chinchillas. The critical level (C) in the rat is similar to that of humans, but higher than that of chinchillas. PMID:25219503

  11. ABR Core examination preparation: results of a survey of fourth-year radiology residents who took the 2013 examination.

    PubMed

    Shetty, Anup S; Grajo, Joseph R; Decker, Summer; Heitkamp, Darel E; DeStigter, Kristen K; Mezwa, Duane G; Deitte, Lori

    2015-01-01

    A survey was administered to fourth-year radiology residents after receiving their results from the first American Board of Radiology (ABR) Core examination in 2013. The purpose was to gather information regarding resources and study strategies to share with program directors and future resident classes. An online survey was distributed to examinees nationwide. The survey included free-response and multiple choice questions that covered examination results, perceived value of enumerated study resources, case-based and didactic teaching conferences, board reviews, study materials for noninterpretive skills, multidisciplinary conference attendance, and free-form comments. Two hundred sixty-six of 1186 residents who took the Core examination responded to the survey. Some resources demonstrated a significant difference in perceived value between residents who passed the examination and residents who failed, including internal board reviews (1.10, P < .01), daily didactic conferences (1.51, P < .01), and daily case conferences (1.43, P < .01). Residents who passed reported that conferences and review sessions at their institutions were modified with multiple choice questions, audience response, and integration of clinical physics and patient safety topics compared to residents who failed. Radiology residents and residency programs have adapted their preparations for the ABR Core examination in a variety of ways. Certain practices and study tools, including daily conferences and internal board reviews, had greater perceived value by residents who passed the examination than by residents who failed. This survey provides insights that can be used to assess and modify current preparation strategies for the ABR Core examination. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

  12. The ototoxic effect of intratympanic terbinafine applied in the middle ear of rats

    PubMed Central

    2013-01-01

    Background Otomycosis is defined as an infection of the external ear canal with fungal agents. The treatment of the disease is cleansing and drying of the external ear canal, identification and treatment of any predisposing factors and application of topical antifungal agents. Terbinafine is used as an antifungal agent to treat otomycosis. We proposed to investigate the probable ototoxic effect of terbinafine solution on auditory brain stem response (ABR) and distortion product otoacoustic emission (DPOAE) when applied intratympanically in the middle ear of rats. Methods The experiment was performed on 30 female Wistar albino rats. Thirty animals were divided into three groups of 10 animals each. 1% terbinafine solution was administered to the first group (group T). The second group (group G) was administered 40 mg/ml gentamicin solution (ototoxic control). The third group (group S) was administered saline solution (negative control). Baseline DPOAE measurements and ABR testing from the left ears were obtained from the animals in all groups under general anesthesia. Ear solutions were applied in the middle ear intratympanically with a dental needle. Treatment was initiated after baseline measurements and repeated once every two days for fifteen days. Results Pre and post-treatment DPOAE responses for all tested frequencies of group T and Group S showed no statistically significant difference. However, the group G demonstrated a significant change in ABR thresholds and DPOAE responses. Conclusions Terbinafine solution is a broad spectrum antifungal agent effective in the treatment of otomycosis. The present study demonstrated that its direct administration in the middle ear of rats does not affect inner ear function as measured by ABR and DPOAE responses. PMID:23663536

  13. Tubulin hyperacetylation is adaptive in cardiac proteotoxicity by promoting autophagy

    PubMed Central

    McLendon, Patrick M.; Ferguson, Bradley S.; Osinska, Hanna; Bhuiyan, Md. Shenuarin; James, Jeanne; McKinsey, Timothy A.; Robbins, Jeffrey

    2014-01-01

    Proteinopathy causes cardiac disease, remodeling, and heart failure but the pathological mechanisms remain obscure. Mutated αB-crystallin (CryABR120G), when expressed only in cardiomyocytes in transgenic (TG) mice, causes desmin-related cardiomyopathy, a protein conformational disorder. The disease is characterized by the accumulation of toxic misfolded protein species that present as perinuclear aggregates known as aggresomes. Previously, we have used the CryABR120G model to determine the underlying processes that result in these pathologic accumulations and to explore potential therapeutic windows that might be used to decrease proteotoxicity. We noted that total ventricular protein is hypoacetylated while hyperacetylation of α-tubulin, a substrate of histone deacetylase 6 (HDAC6) occurs. HDAC6 has critical roles in protein trafficking and autophagy, but its function in the heart is obscure. Here, we test the hypothesis that tubulin acetylation is an adaptive process in cardiomyocytes. By modulating HDAC6 levels and/or activity genetically and pharmacologically, we determined the effects of tubulin acetylation on aggregate formation in CryABR120G cardiomyocytes. Increasing HDAC6 accelerated aggregate formation, whereas siRNA-mediated knockdown or pharmacological inhibition ameliorated the process. HDAC inhibition in vivo induced tubulin hyperacetylation in CryABR120G TG hearts, which prevented aggregate formation and significantly improved cardiac function. HDAC6 inhibition also increased autophagic flux in cardiomyocytes, and increased autophagy in the diseased heart correlated with increased tubulin acetylation, suggesting that autophagy induction might underlie the observed cardioprotection. Taken together, our data suggest a mechanistic link between tubulin hyperacetylation and autophagy induction and points to HDAC6 as a viable therapeutic target in cardiovascular disease. PMID:25404307

  14. Preservation of auditory brainstem response thresholds after cochleostomy and titanium microactuator implantation in the lateral wall of cat scala tympani.

    PubMed

    Lesinski, S George; Prewitt, Jessica; Bray, Victor; Aravamudhan, Radhika; Bermeo Blanco, Oscar A; Farmer-Fedor, Brenda L; Ward, Jonette A

    2014-04-01

    The safety of implanting a titanium microactuator into the lateral wall of cat scala tympani was assessed by comparing preoperative and postoperative auditory brainstem response (ABR) thresholds for 1 to 3 months. The safety of directly stimulating cochlear perilymph with an implantable hearing system requires maintaining preoperative hearing levels. This cat study is an essential step in the development of the next generation of fully implantable hearing devices for humans. Following GLP surgical standards, a 1-mm cochleostomy was drilled into the lateral wall of the scala tympani, and a nonfunctioning titanium anchor/microactuator assembly was inserted in 8 cats. The scala media was damaged in the 1 cat. ABR thresholds with click and 4- and 8-kHz stimuli were measured preoperatively and compared with postoperative thresholds at 1, 2, and 3 months. Nonimplanted ear thresholds were also measured to establish statistical significance for threshold shifts (>28.4 dB). Two audiologists independently interpreted thresholds. Postoperatively, 7 cats implanted in the scala tympani demonstrated no significant ABR threshold shift for click stimulus; one shifted ABR thresholds to 4- and 8-kHz stimuli. The eighth cat, with surgical damage to the scala media, maintained stable click threshold but had a significant shift to 4- and 8-kHz stimuli. This cat study provides no evidence of worsening hearing thresholds after fenestration of the scala tympani and insertion of a titanium anchor/microactuator, provided there is no surgical trauma to the scala media and the implanted device is securely anchored in the cochleostomy. These 2 issues have been resolved in the development of a fully implantable hearing system for humans. The long-term hearing stability (combined with histologic studies) reaffirm that the microactuator is well tolerated by the cat cochlea.

  15. 10 CFR 607.620 - Cooperative agreement.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Cooperative agreement. 607.620 Section 607.620 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 607.620 Cooperative agreement. Cooperative agreement means an award of...

  16. Single-molecule FRET studies of the cooperative and non-cooperative binding kinetics of the bacteriophage T4 single-stranded DNA binding protein (gp32) to ssDNA lattices at replication fork junctions

    PubMed Central

    Lee, Wonbae; Gillies, John P.; Jose, Davis; Israels, Brett A.; von Hippel, Peter H.; Marcus, Andrew H.

    2016-01-01

    Gene 32 protein (gp32) is the single-stranded (ss) DNA binding protein of the bacteriophage T4. It binds transiently and cooperatively to ssDNA sequences exposed during the DNA replication process and regulates the interactions of the other sub-assemblies of the replication complex during the replication cycle. We here use single-molecule FRET techniques to build on previous thermodynamic studies of gp32 binding to initiate studies of the dynamics of the isolated and cooperative binding of gp32 molecules within the replication complex. DNA primer/template (p/t) constructs are used as models to determine the effects of ssDNA lattice length, gp32 concentration, salt concentration, binding cooperativity and binding polarity at p/t junctions. Hidden Markov models (HMMs) and transition density plots (TDPs) are used to characterize the dynamics of the multi-step assembly pathway of gp32 at p/t junctions of differing polarity, and show that isolated gp32 molecules bind to their ssDNA targets weakly and dissociate quickly, while cooperatively bound dimeric or trimeric clusters of gp32 bind much more tightly, can ‘slide’ on ssDNA sequences, and exhibit binding dynamics that depend on p/t junction polarities. The potential relationships of these binding dynamics to interactions with other components of the T4 DNA replication complex are discussed. PMID:27694621

  17. 50 CFR 401.9 - Payments to cooperators.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A ANADROMOUS FISHERIES... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Payments to cooperators. 401.9 Section 401.9 Wildlife and Fisheries JOINT REGULATIONS (UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF...

  18. 7 CFR 1001.18 - Cooperative association.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Cooperative association. 1001.18 Section 1001.18 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE NORTHEAST MARKETING AREA Order Regulating...

  19. 7 CFR 1.76 - Department cooperation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 1 2011-01-01 2011-01-01 false Department cooperation. 1.76 Section 1.76 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Cooperative Production of Television Films § 1.76 Department cooperation. When the producer agrees to meet the above stipulations to the...

  20. 7 CFR 1.76 - Department cooperation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 1 2014-01-01 2014-01-01 false Department cooperation. 1.76 Section 1.76 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Cooperative Production of Television Films § 1.76 Department cooperation. When the producer agrees to meet the above stipulations to the...

  1. 7 CFR 1.76 - Department cooperation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 1 2012-01-01 2012-01-01 false Department cooperation. 1.76 Section 1.76 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Cooperative Production of Television Films § 1.76 Department cooperation. When the producer agrees to meet the above stipulations to the...

  2. 7 CFR 1.76 - Department cooperation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Department cooperation. 1.76 Section 1.76 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Cooperative Production of Television Films § 1.76 Department cooperation. When the producer agrees to meet the above stipulations to the...

  3. The content of our cooperation, not the color of our skin: an alliance detection system regulates categorization by coalition and race, but not sex.

    PubMed

    Pietraszewski, David; Cosmides, Leda; Tooby, John

    2014-01-01

    Humans in all societies form and participate in cooperative alliances. To successfully navigate an alliance-laced world, the human mind needs to detect new coalitions and alliances as they emerge, and predict which of many potential alliance categories are currently organizing an interaction. We propose that evolution has equipped the mind with cognitive machinery that is specialized for performing these functions: an alliance detection system. In this view, racial categories do not exist because skin color is perceptually salient; they are constructed and regulated by the alliance system in environments where race predicts social alliances and divisions. Early tests using adversarial alliances showed that the mind spontaneously detects which individuals are cooperating against a common enemy, implicitly assigning people to rival alliance categories based on patterns of cooperation and competition. But is social antagonism necessary to trigger the categorization of people by alliance--that is, do we cognitively link A and B into an alliance category only because they are jointly in conflict with C and D? We report new studies demonstrating that peaceful cooperation can trigger the detection of new coalitional alliances and make race fade in relevance. Alliances did not need to be marked by team colors or other perceptually salient cues. When race did not predict the ongoing alliance structure, behavioral cues about cooperative activities up-regulated categorization by coalition and down-regulated categorization by race, sometimes eliminating it. Alliance cues that sensitively regulated categorization by coalition and race had no effect on categorization by sex, eliminating many alternative explanations for the results. The results support the hypothesis that categorizing people by their race is a reversible product of a cognitive system specialized for detecting alliance categories and regulating their use. Common enemies are not necessary to erase important social boundaries; peaceful cooperation can have the same effect.

  4. The Content of Our Cooperation, Not the Color of Our Skin: An Alliance Detection System Regulates Categorization by Coalition and Race, but Not Sex

    PubMed Central

    Pietraszewski, David; Cosmides, Leda; Tooby, John

    2014-01-01

    Humans in all societies form and participate in cooperative alliances. To successfully navigate an alliance-laced world, the human mind needs to detect new coalitions and alliances as they emerge, and predict which of many potential alliance categories are currently organizing an interaction. We propose that evolution has equipped the mind with cognitive machinery that is specialized for performing these functions: an alliance detection system. In this view, racial categories do not exist because skin color is perceptually salient; they are constructed and regulated by the alliance system in environments where race predicts social alliances and divisions. Early tests using adversarial alliances showed that the mind spontaneously detects which individuals are cooperating against a common enemy, implicitly assigning people to rival alliance categories based on patterns of cooperation and competition. But is social antagonism necessary to trigger the categorization of people by alliance—that is, do we cognitively link A and B into an alliance category only because they are jointly in conflict with C and D? We report new studies demonstrating that peaceful cooperation can trigger the detection of new coalitional alliances and make race fade in relevance. Alliances did not need to be marked by team colors or other perceptually salient cues. When race did not predict the ongoing alliance structure, behavioral cues about cooperative activities up-regulated categorization by coalition and down-regulated categorization by race, sometimes eliminating it. Alliance cues that sensitively regulated categorization by coalition and race had no effect on categorization by sex, eliminating many alternative explanations for the results. The results support the hypothesis that categorizing people by their race is a reversible product of a cognitive system specialized for detecting alliance categories and regulating their use. Common enemies are not necessary to erase important social boundaries; peaceful cooperation can have the same effect. PMID:24520394

  5. An N-terminally truncated form of cyclic GMP-dependent protein kinase Iα (PKG Iα) is monomeric and autoinhibited and provides a model for activation.

    PubMed

    Moon, Thomas M; Sheehe, Jessica L; Nukareddy, Praveena; Nausch, Lydia W; Wohlfahrt, Jessica; Matthews, Dwight E; Blumenthal, Donald K; Dostmann, Wolfgang R

    2018-05-25

    The type I cGMP-dependent protein kinases (PKG I) serve essential physiological functions, including smooth muscle relaxation, cardiac remodeling, and platelet aggregation. These enzymes form homodimers through their N-terminal dimerization domains, a feature implicated in regulating their cooperative activation. Previous investigations into the activation mechanisms of PKG I isoforms have been largely influenced by structures of the cAMP-dependent protein kinase (PKA). Here, we examined PKG Iα activation by cGMP and cAMP by engineering a monomeric form that lacks N-terminal residues 1-53 (Δ53). We found that the construct exists as a monomer as assessed by whole-protein MS, size-exclusion chromatography, and small-angle X-ray scattering (SAXS). Reconstruction of the SAXS 3D envelope indicates that Δ53 has a similar shape to the heterodimeric RIα-C complex of PKA. Moreover, we found that the Δ53 construct is autoinhibited in its cGMP-free state and can bind to and be activated by cGMP in a manner similar to full-length PKG Iα as assessed by surface plasmon resonance (SPR) spectroscopy. However, we found that the Δ53 variant does not exhibit cooperative activation, and its cyclic nucleotide selectivity is diminished. These findings support a model in which, despite structural similarities, PKG Iα activation is distinct from that of PKA, and its cooperativity is driven by in trans interactions between protomers. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Negative regulation of AMP-activated protein kinase (AMPK) activity by macrophage migration inhibitory factor (MIF) family members in non-small cell lung carcinomas.

    PubMed

    Brock, Stephanie E; Rendon, Beatriz E; Yaddanapudi, Kavitha; Mitchell, Robert A

    2012-11-02

    AMP-activated protein kinase (AMPK) is a nutrient- and metabolic stress-sensing enzyme activated by the tumor suppressor kinase, LKB1. Because macrophage migration inhibitory factor (MIF) and its functional homolog, d-dopachrome tautomerase (d-DT), have protumorigenic functions in non-small cell lung carcinomas (NSCLCs) but have AMPK-activating properties in nonmalignant cell types, we set out to investigate this apparent paradox. Our data now suggest that, in contrast to MIF and d-DTs AMPK-activating properties in nontransformed cells, MIF and d-DT act cooperatively to inhibit steady-state phosphorylation and activation of AMPK in LKB1 wild type and LKB1 mutant human NSCLC cell lines. Our data further indicate that MIF and d-DT, acting through their shared cell surface receptor, CD74, antagonize NSCLC AMPK activation by maintaining glucose uptake, ATP production, and redox balance, resulting in reduced Ca(2+)/calmodulin-dependent kinase kinase β-dependent AMPK activation. Combined, these studies indicate that MIF and d-DT cooperate to inhibit AMPK activation in an LKB1-independent manner.

  7. Randomized, Prospective, Three-Arm Study to Confirm the Auditory Safety and Efficacy of Artemether-Lumefantrine in Colombian Patients with Uncomplicated Plasmodium falciparum Malaria

    PubMed Central

    Carrasquilla, Gabriel; Barón, Clemencia; Monsell, Edwin M.; Cousin, Marc; Walter, Verena; Lefèvre, Gilbert; Sander, Oliver; Fisher, Laurel M.

    2012-01-01

    The safety of artemether-lumefantrine in patients with acute, uncomplicated Plasmodium falciparum malaria was investigated prospectively using the auditory brainstem response (ABR) and pure-tone thresholds. Secondary outcomes included polymerase chain reaction-corrected cure rates. Patients were randomly assigned in a 3:1:1 ratio to either artemether-lumefantrine (N = 159), atovaquone-proguanil (N = 53), or artesunate-mefloquine (N = 53). The null hypothesis (primary outcome), claiming that the percentage of patients with a baseline to Day-7 ABR Wave III latency increase of > 0.30 msec is ≥ 15% after administration of artemether-lumefantrine, was rejected; 2.6% of patients (95% confidence interval: 0.7–6.6) exceeded 0.30 msec, i.e., significantly below 15% (P < 0.0001). A model-based analysis found no apparent relationship between drug exposure and ABR change. In all three groups, average improvements (2–4 dB) in pure-tone thresholds were observed, and polymerase chain reaction-corrected cure rates were > 95% to Day 42. The results support the continued safe and efficacious use of artemether-lumefantrine in uncomplicated falciparum malaria. PMID:22232454

  8. Randomized, prospective, three-arm study to confirm the auditory safety and efficacy of artemether-lumefantrine in Colombian patients with uncomplicated Plasmodium falciparum malaria.

    PubMed

    Carrasquilla, Gabriel; Barón, Clemencia; Monsell, Edwin M; Cousin, Marc; Walter, Verena; Lefèvre, Gilbert; Sander, Oliver; Fisher, Laurel M

    2012-01-01

    The safety of artemether-lumefantrine in patients with acute, uncomplicated Plasmodium falciparum malaria was investigated prospectively using the auditory brainstem response (ABR) and pure-tone thresholds. Secondary outcomes included polymerase chain reaction-corrected cure rates. Patients were randomly assigned in a 3:1:1 ratio to either artemether-lumefantrine (N = 159), atovaquone-proguanil (N = 53), or artesunate-mefloquine (N = 53). The null hypothesis (primary outcome), claiming that the percentage of patients with a baseline to Day-7 ABR Wave III latency increase of > 0.30 msec is ≥ 15% after administration of artemether-lumefantrine, was rejected; 2.6% of patients (95% confidence interval: 0.7-6.6) exceeded 0.30 msec, i.e., significantly below 15% (P < 0.0001). A model-based analysis found no apparent relationship between drug exposure and ABR change. In all three groups, average improvements (2-4 dB) in pure-tone thresholds were observed, and polymerase chain reaction-corrected cure rates were > 95% to Day 42. The results support the continued safe and efficacious use of artemether-lumefantrine in uncomplicated falciparum malaria.

  9. Test-retest reliability of auditory brainstem responses to chirp stimuli in newborns.

    PubMed

    Cobb, Kensi M; Stuart, Andrew

    2014-11-01

    The purpose of this study was to examine the test-retest reliability of auditory brainstem responses (ABRs) to air- and bone-conducted chirp stimuli in newborns as a function of intensity. A repeated measures quasi-experimental design was employed. Thirty healthy newborns participated. ABRs were evoked using 60, 45, and 30 dB nHL air-conducted CE-Chirps and 45, 30, and 15 dB nHL bone-conducted CE-Chirps at a rate of 57.7/s. Measures were repeated by a second tester. Statistically significant correlations (p <.0001) and predictive linear relations (p <.0001) were found between testers for wave V latencies and amplitudes to air- and bone-conducted CE-Chirps. There were also no statistically significant differences between testers with wave V latencies and amplitudes to air- and bone-conducted CE-Chirps (p >.05). As expected, significant differences in wave V latencies and amplitudes were seen as a function of stimulus intensity for air- and bone-conducted CE-Chirps (p <.0001). These results suggest that ABRs to air- and bone-conducted CE-Chirps can be reliably repeated in newborns with different testers. The CE-Chirp may be valuable for both screening and diagnostic audiologic assessments of newborns.

  10. Acceptance and relationship context: a model of substance use disorder treatment outcome.

    PubMed

    Gifford, Elizabeth V; Ritsher, Jennifer B; McKellar, John D; Moos, Rudolf H

    2006-08-01

    This study presented and tested a model of behavior change in long-term substance use disorder recovery, the acceptance and relationship context (ARC) model. The model specifies that acceptance-based behavior and constructive social relationships lead to recovery, and that treatment programs with supportive, involved relationships facilitate the development of these factors. This study used a prospective longitudinal naturalistic design and controlled for baseline levels of study variables. The model was tested on a sample of 2549 patients in 15 residential substance use disorder treatment programs. Acceptance-based responding (ABR), social relationship quality (SRQ), treatment program alliance (TPA) and substance use-related impairment were assessed using interviews and self-report questionnaires. TPA predicted ABR and SRQ and, in turn, ABR predicted better 2-year and 5-year treatment outcomes. The baseline-controlled model accounted for 41% of the variance in outcome at 2-year follow-up and 28% of the variance in outcome at 5-year follow-up. CONCLUSIONS Patients from treatment programs with an affiliative relationship network are more likely to respond adaptively to internal states associated previously with substance use, develop constructive social relationships and achieve long-term treatment benefits.

  11. SU-B-213-06: Development of ABR Examination Questions

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

    Allison, J.

    2015-06-15

    The North American medical physics community validates the education received by medical physicists and the clinical qualifications for medical physicists through accreditation of educational programs and certification of medical physicists. Medical physics educational programs (graduate education and residency education) are accredited by the Commission on Accreditation of Medical Physics Education Programs (CAMPEP), whereas medical physicists are certified by several organizations, the most familiar of which is the American Board of Radiology (ABR). In order for an educational program to become accredited or a medical physicist to become certified, the applicant must meet certain specified standards set by the appropriate organization.more » In this Symposium, representatives from both CAMPEP and the ABR will describe the process by which standards are established as well as the process by which qualifications of candidates for accreditation or certification are shown to be compliant with these standards. The Symposium will conclude with a panel discussion. Learning Objectives: Recognize the difference between accreditation of an educational program and certification of an individual Identify the two organizations primarily responsible for these tasks Describe the development of educational standards Describe the process by which examination questions are developed GS is Executive Secretary of CAMPEP.« less

  12. Consensus Statement of the Indian Academy of Pediatrics on Newborn Hearing Screening.

    PubMed

    Paul, Abraham; Prasad, Chhaya; Kamath, S S; Dalwai, Samir; C Nair, M K; Pagarkar, Waheeda

    2017-08-15

    Hearing impairment is one of the most critical sensory impairments with significant social and psychological consequences. Evidence-based, standardized national guidelines are needed for professionals to screen for hearing impairment during the neonatal period. The meeting on formulation of national consensus guidelines on developmental disorders was organized by Indian Academy of Pediatrics in Mumbai, on 18th and 19th December, 2015. The invited experts included Pediatricians, Developmental Pediatricians, Pediatric Neurologists and Clinical Psychologists. The participants framed guidelines after extensive discussions. To provide guidelines on newborn hearing screening in India. The first screening should be conducted before the neonate's discharge from the hospital - if it 'fails', then it should be repeated after four weeks, or at first immunization visit. If it 'fails' again, then Auditory Brainstem Response (ABR) audiometry should be conducted. All babies admitted to intensive care unit should be screened via ABR. All babies with abnormal ABR should undergo detailed evaluation, hearing aid fitting and auditory rehabilitation, before six months of age. The goal is to screen newborn babies before one month of age, diagnose hearing loss before three months of age and start intervention before six months of age.

  13. SU-B-213-05: Development of ABR Certification Standards

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

    Seibert, J.

    2015-06-15

    The North American medical physics community validates the education received by medical physicists and the clinical qualifications for medical physicists through accreditation of educational programs and certification of medical physicists. Medical physics educational programs (graduate education and residency education) are accredited by the Commission on Accreditation of Medical Physics Education Programs (CAMPEP), whereas medical physicists are certified by several organizations, the most familiar of which is the American Board of Radiology (ABR). In order for an educational program to become accredited or a medical physicist to become certified, the applicant must meet certain specified standards set by the appropriate organization.more » In this Symposium, representatives from both CAMPEP and the ABR will describe the process by which standards are established as well as the process by which qualifications of candidates for accreditation or certification are shown to be compliant with these standards. The Symposium will conclude with a panel discussion. Learning Objectives: Recognize the difference between accreditation of an educational program and certification of an individual Identify the two organizations primarily responsible for these tasks Describe the development of educational standards Describe the process by which examination questions are developed GS is Executive Secretary of CAMPEP.« less

  14. NASA's Arctic-Boreal Vulnerability Experiment: A large-scale study of environmental change in Western North America and its implications for ecological systems and society

    NASA Astrophysics Data System (ADS)

    Kasischke, E. S.; Hayes, D. J.; Griffith, P. C.; Larson, E. K.; Wickland, D. E.

    2013-12-01

    Climate change in high northern latitudes is unfolding faster than anywhere else on Earth, resulting in widespread changes in landscape structure and ecosystem function in the Arctic-Boreal Region (ABR). Recognizing its sensitivity, vulnerability and global importance, national- and international-level scientific efforts are now advancing our ability to observe, understand and model the complex, multi-scale processes that drive the ABR's natural and social systems. Long at the edge of our mental map of the world, environmental change in the ABR is increasingly becoming the focus of numerous policy discussions at the highest levels of decision-making. To improve our understanding of environmental change and its impacts in the ABR, the Terrestrial Ecology Program of the U.S. National Aeronautics and Space Administration (NASA) is planning its next major field campaign for Western Canada and Alaska. The field campaign will be based on the Arctic-Boreal Vulnerability Experiment (ABoVE) concept as described in the Revised Executive Summary from the ABoVE Scoping Study Report. The original Scoping Study Report provided the proof-of-concept demonstration of scientific importance and feasibility for this large-scale study. In early 2013, NASA announced the selection of the ABoVE Science Definition Team, which is charged with developing the Concise Experiment Plan for the campaign. Here, we outline the conceptual basis for ABoVE and present the compelling rationale explaining the scientific and societal importance of the study. We present the current status of the planning process, which includes development of the science questions to drive ABoVE research; the study design for the field campaign to address them; and the interagency and international collaborations necessary for implementation. The ABoVE study will focus on 1) developing a fuller understanding of ecosystem vulnerability to climate change in the ABR, and 2) providing the scientific information required to develop options for societal responses to the impacts of these changes. The field campaign will emphasize research that integrates data collected by airborne and spaceborne sensors with information obtained from field studies and ground-based observations. Other key components of ABoVE research include the process-level analyses, scientific syntheses, and modeling needed for understanding ecosystem responses and societal implications.

  15. [Relationships between electrophysiological characteristic of speech evoked auditory brainstem response and Mandarin monosyllable discriminative ability at different hearing impairment].

    PubMed

    Fu, Q Y; Liang, Y; Zou, A; Wang, T; Zhao, X D; Wan, J

    2016-04-07

    To investigate the relationships between electrophysiological characteristic of speech evoked auditory brainstem response(s-ABR) and Mandarin phonetically balanced maximum(PBmax) at different hearing impairment, so as to provide more clues for the mechanism of speech cognitive behavior. Forty-one ears in 41 normal hearing adults(NH), thirty ears in 30 conductive hearing loss patients(CHL) and twenty-seven ears in 27 sensorineural hearing loss patients(SNHL) were included in present study. The speech discrimination scores were obtained by Mandarin phonemic-balanced monosyllable lists via speech audiometric software. Their s-ABRs were recorded with speech syllables /da/ with the intensity of phonetically balanced maximum(PBmax). The electrophysiological characteristic of s-ABR, as well as the relationships between PBmax and s-ABR parameters including latency in time domain, fundamental frequency(F0) and first formant(F1) in frequency domain were analyzed statistically. All subjects completed good speech perception tests and PBmax of CHL and SNHL had no significant difference (P>0.05), but both significantly less than that of NH (P<0.05). While divided the subjects into three groups by 90%

  16. Evaluation of auditory brain stems evoked response in newborns with pathologic hyperbilirubinemia in mashhad, iran.

    PubMed

    Okhravi, Tooba; Tarvij Eslami, Saeedeh; Hushyar Ahmadi, Ali; Nassirian, Hossain; Najibpour, Reza

    2015-02-01

    Neonatal jaundice is a common cause of sensorneural hearing loss in children. We aimed to detect the neurotoxic effects of pathologic hyperbilirubinemia on brain stem and auditory tract by auditory brain stem evoked response (ABR) which could predict early effects of hyperbilirubinemia. This case-control study was performed on newborns with pathologic hyperbilirubinemia. The inclusion criteria were healthy term and near term (35 - 37 weeks) newborns with pathologic hyperbilirubinemia with serum bilirubin values of ≥ 7 mg/dL, ≥ 10 mg/dL and ≥14 mg/dL at the first, second and third-day of life, respectively, and with bilirubin concentration ≥ 18 mg/dL at over 72 hours of life. The exclusion criteria included family history and diseases causing sensorineural hearing loss, use of auto-toxic medications within the preceding five days, convulsion, congenital craniofacial anomalies, birth trauma, preterm newborns < 35 weeks old, birth weight < 1500 g, asphyxia, and mechanical ventilations for five days or more. A total of 48 newborns with hyperbilirubinemia met the enrolment criteria as the case group and 49 healthy newborns as the control group, who were hospitalized in a university educational hospital (22 Bahaman), in a north-eastern city of Iran, Mashhad. ABR was performed on both groups. The evaluated variable factors were latency time, inter peak intervals time, and loss of waves. The mean latencies of waves I, III and V of ABR were significantly higher in the pathologic hyperbilirubinemia group compared with the controls (P < 0.001). In addition, the mean interpeak intervals (IPI) of waves I-III, I-V and III-V of ABR were significantly higher in the pathologic hyperbilirubinemia group compared with the controls (P < 0.001). For example, the mean latencies time of wave I was significantly higher in right ear of the case group than in controls (2.16 ± 0.26 vs. 1.77 ± 0.15 milliseconds, respectively) (P < 0.001). Pathologic hyperbilirubinemia causes acute disorder on brain stem function; therefore, early diagnosis of neonatal jaundice for prevention of bilirubin neurotoxic effects is essential. As national neonatal hearing screening in not yet established in Iran, we recommend performing ABR for screening of bilirubin neurotoxicity in all cases with hyperbilirubinemia.

  17. Variants at serotonin transporter and 2A receptor genes predict cooperative behavior differentially according to presence of punishment.

    PubMed

    Schroeder, Kari B; McElreath, Richard; Nettle, Daniel

    2013-03-05

    Punishment of free-riding has been implicated in the evolution of cooperation in humans, and yet mechanisms for punishment avoidance remain largely uninvestigated. Individual variation in these mechanisms may stem from variation in the serotonergic system, which modulates processing of aversive stimuli. Functional serotonin gene variants have been associated with variation in the processing of aversive stimuli and widely studied as risk factors for psychiatric disorders. We show that variants at the serotonin transporter gene (SLC6A4) and serotonin 2A receptor gene (HTR2A) predict contributions to the public good in economic games, dependent upon whether contribution behavior can be punished. Participants with a variant at the serotonin transporter gene contribute more, leading to group-level differences in cooperation, but this effect dissipates in the presence of punishment. When contribution behavior can be punished, those with a variant at the serotonin 2A receptor gene contribute more than those without it. This variant also predicts a more stressful experience of the games. The diversity of institutions (including norms) that govern cooperation and punishment may create selective pressures for punishment avoidance that change rapidly across time and space. Variant-specific epigenetic regulation of these genes, as well as population-level variation in the frequencies of these variants, may facilitate adaptation to local norms of cooperation and punishment.

  18. Variants at serotonin transporter and 2A receptor genes predict cooperative behavior differentially according to presence of punishment

    PubMed Central

    Schroeder, Kari B.; McElreath, Richard; Nettle, Daniel

    2013-01-01

    Punishment of free-riding has been implicated in the evolution of cooperation in humans, and yet mechanisms for punishment avoidance remain largely uninvestigated. Individual variation in these mechanisms may stem from variation in the serotonergic system, which modulates processing of aversive stimuli. Functional serotonin gene variants have been associated with variation in the processing of aversive stimuli and widely studied as risk factors for psychiatric disorders. We show that variants at the serotonin transporter gene (SLC6A4) and serotonin 2A receptor gene (HTR2A) predict contributions to the public good in economic games, dependent upon whether contribution behavior can be punished. Participants with a variant at the serotonin transporter gene contribute more, leading to group-level differences in cooperation, but this effect dissipates in the presence of punishment. When contribution behavior can be punished, those with a variant at the serotonin 2A receptor gene contribute more than those without it. This variant also predicts a more stressful experience of the games. The diversity of institutions (including norms) that govern cooperation and punishment may create selective pressures for punishment avoidance that change rapidly across time and space. Variant-specific epigenetic regulation of these genes, as well as population-level variation in the frequencies of these variants, may facilitate adaptation to local norms of cooperation and punishment. PMID:23431136

  19. Sema4D, the ligand for Plexin B1, suppresses c-Met activation and migration and promotes melanocyte survival and growth

    PubMed Central

    Soong, Joanne; Chen, Yulin; Shustef, Elina; Scott, Glynis

    2011-01-01

    Semaphorins are secreted and membrane bound proteins involved in neural pathfinding, organogenesis, and tumor progression, through Plexin and neuropilins receptors. We recently reported that Plexin B1, the Semaphorin 4D receptor, is a tumor suppressor protein for melanoma, in part, through inhibition of the oncogenic c-Met tyrosine kinase receptor. In this report we show that Sema4D is a protective paracrine factor for normal human melanocyte survival in response to ultraviolet irradiation, that it stimulates proliferation, and regulates the activity of the c-Met receptor. c-Met receptor signaling stimulates melanocyte migration, in part through down-regulation of the cell adhesion molecule E-cadherin. Sema4D suppressed activation of c-Met in response to its ligand hepatocyte growth factor (HGF), and partially blocked the suppressive effects of HGF on E-cadherin expression in melanocytes and HGF-dependent migration. These data demonstrate a role for Plexin B1 in maintenance of melanocyte survival and proliferation in the skin, and suggest that Semaphorin 4D and Plexin B1 act cooperatively with HGF and c-Met to regulate c-Met dependent effects in human melanocytes. Because our data show that Plexin B1 is profoundly down-regulated by UVB in melanocytes, loss of Plexin B1 may accentuate HGF dependent effects on melanocytes, including melanocyte migration. PMID:22189792

  20. Unified Strouhal-Reynolds number relationship for laminar vortex streets generated by different-shaped obstacles.

    PubMed

    Kim, Ildoo; Wu, X L

    2015-10-01

    A structure-based Strouhal-Reynolds number relationship, St=1/(A+B/Re), has been recently proposed based on observations of laminar vortex shedding from circular cylinders in a flowing soap film. Since the new St-Re relation was derived from a general physical consideration, it raises the possibility that it may be applicable to vortex shedding from bodies other than circular ones. The work presented herein provides experimental evidence that this is the case. Our measurements also show that, in the asymptotic limit (Re→∞), St(∞)=1/A≃0.21 is constant independent of rod shapes, leaving B the only parameter that is shape dependent.

  1. Therapeutic Ultrasound Bypasses Canonical Syndecan-4 Signaling to Activate Rac1*S⃞

    PubMed Central

    Mahoney, Claire M.; Morgan, Mark R.; Harrison, Andrew; Humphries, Martin J.; Bass, Mark D.

    2009-01-01

    The application of pulsed, low intensity ultrasound is emerging as a potent therapy for the treatment of complex bone fractures and tissue damage. Ultrasonic stimuli accelerate fracture healing by up to 40% and enhance tendon and ligament healing by promoting cell proliferation, migration, and matrix synthesis through an unresolved mechanism. Ultrasound treatment also induces closure of nonunion fractures, at a success rate (85% of cases) similar to that of surgical intervention (68-96%) while avoiding the complications associated with surgery. The regulation of cell adhesion necessary for wound healing depends on cooperative engagement of the extracellular matrix receptors, integrin and syndecan, as exemplified by the wound healing defects observed in syndecan- and integrin-knock-out mice. This report distinguishes the influence of ultrasound on signals downstream of the prototypic fibronectin receptors, α5β1 integrin and syndecan-4, which cooperate to regulate Rac1 and RhoA. Ultrasonic stimulation fails to activate integrins or induce cell spreading on poor, electrostatic ligands. By contrast, ultrasound treatment overcomes the necessity of engagement or expression of syndecan-4 during the process of focal adhesion formation, which normally requires simultaneous engagement of both receptors. Ultrasound exerts an influence downstream of syndecan-4 and PKCα to specifically activate Rac1, itself a critical regulator of tissue repair, and to a lesser extent RhoA. The ability of ultrasound to bypass syndecan-4 signaling, which is known to facilitate efficient tissue repair, explains the reduction in healing times observed in ultrasound-treated patients. By substituting for one of the key axes of adhesion-dependent signaling, ultrasound therapy has considerable potential as a clinical technique. PMID:19147498

  2. Inhibitors of histone demethylation and histone deacetylation cooperate in regulating gene expression and inhibiting growth in human breast cancer cells

    PubMed Central

    Vasilatos, Shauna N.; Boric, Lamia; Shaw, Patrick G.; Davidson, Nancy E.

    2013-01-01

    Abnormal activities of histone lysine demethylases (KDMs) and lysine deacetylases (HDACs) are associated with aberrant gene expression in breast cancer development. However, the precise molecular mechanisms underlying the crosstalk between KDMs and HDACs in chromatin remodeling and regulation of gene transcription are still elusive. In this study, we showed that treatment of human breast cancer cells with inhibitors targeting the zinc cofactor dependent class I/II HDAC, but not NAD+ dependent class III HDAC, led to significant increase of H3K4me2 which is a specific substrate of histone lysine-specific demethylase 1 (LSD1) and a key chromatin mark promoting transcriptional activation. We also demonstrated that inhibition of LSD1 activity by a pharmacological inhibitor, pargyline, or siRNA resulted in increased acetylation of H3K9 (AcH3K9). However, siRNA knockdown of LSD2, a homolog of LSD1, failed to alter the level of AcH3K9, suggesting that LSD2 activity may not be functionally connected with HDAC activity. Combined treatment with LSD1 and HDAC inhibitors resulted in enhanced levels of H3K4me2 and AcH3K9, and exhibited synergistic growth inhibition of breast cancer cells. Finally, microarray screening identified a unique subset of genes whose expression was significantly changed by combination treatment with inhibitors of LSD1 and HDAC. Our study suggests that LSD1 intimately interacts with histone deacetylases in human breast cancer cells. Inhibition of histone demethylation and deacetylation exhibits cooperation and synergy in regulating gene expression and growth inhibition, and may represent a promising and novel approach for epigenetic therapy of breast cancer. PMID:21452019

  3. Calcium Influx and Release Cooperatively Regulate AChR Patterning and Motor Axon Outgrowth during Neuromuscular Junction Formation.

    PubMed

    Kaplan, Mehmet Mahsum; Sultana, Nasreen; Benedetti, Ariane; Obermair, Gerald J; Linde, Nina F; Papadopoulos, Symeon; Dayal, Anamika; Grabner, Manfred; Flucher, Bernhard E

    2018-06-26

    Formation of synapses between motor neurons and muscles is initiated by clustering of acetylcholine receptors (AChRs) in the center of muscle fibers prior to nerve arrival. This AChR patterning is considered to be critically dependent on calcium influx through L-type channels (Ca V 1.1). Using a genetic approach in mice, we demonstrate here that either the L-type calcium currents (LTCCs) or sarcoplasmic reticulum (SR) calcium release is necessary and sufficient to regulate AChR clustering at the onset of neuromuscular junction (NMJ) development. The combined lack of both calcium signals results in loss of AChR patterning and excessive nerve branching. In the absence of SR calcium release, the severity of synapse formation defects inversely correlates with the magnitude of LTCCs. These findings highlight the importance of activity-dependent calcium signaling in early neuromuscular junction formation and indicate that both LTCC and SR calcium release individually support proper innervation of muscle by regulating AChR patterning and motor axon outgrowth. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Dynamic Control of Excitatory Synapse Development by a Rac1 GEF/GAP Regulatory Complex

    PubMed Central

    Um, Kyongmi; Niu, Sanyong; Duman, Joseph G.; Cheng, Jinxuan; Tu, Yen-Kuei; Schwechter, Brandon; Liu, Feng; Hiles, Laura; Narayanan, Anjana; Ash, Ryan T.; Mulherkar, Shalaka; Alpadi, Kannan; Smirnakis, Stelios M.; Tolias, Kimberley F.

    2014-01-01

    SUMMARY The small GTPase Rac1 orchestrates actin-dependent remodeling essential for numerous cellular processes including synapse development. While precise spatiotemporal regulation of Rac1 is necessary for its function, little is known about the mechanisms that enable Rac1 activators (GEFs) and inhibitors (GAPs) to act in concert to regulate Rac1 signaling. Here we identify a regulatory complex composed of a Rac-GEF (Tiam1) and a Rac-GAP (Bcr) that cooperate to control excitatory synapse development. Disruption of Bcr function within this complex increases Rac1 activity and dendritic spine remodeling, resulting in excessive synaptic growth that is rescued by Tiam1 inhibition. Notably, EphB receptors utilize the Tiam1-Bcr complex to control synaptogenesis. Following EphB activation, Tiam1 induces Rac1-dependent spine formation, whereas Bcr prevents Rac1-mediated receptor internalization, promoting spine growth over retraction. The finding that a Rac-specific GEF/GAP complex is required to maintain optimal levels of Rac1 signaling provides an important insight into the regulation of small GTPases. PMID:24960694

  5. Targeted Mutation of the Gene for Cellular Glutathione Peroxidase (Gpx1) Increases Noise-Induced Hearing Loss in Mice

    PubMed Central

    McFadden, Sandra L.; Ding, Da-Lian; Lear, Patricia M.; Ho, Ye-Shih

    2000-01-01

    Reactive oxygen species (ROS) and oxidative stress have been implicated in cochlear injury following loud noise and ototoxins. Genetic mutations that impair antioxidant defenses would be expected to increase cochlear injury following acute insults and to contribute to cumulative injury that presents as age-related hearing loss. We examined whether genetically based deficiency of cellular glutathione peroxidase, a major antioxidant enzyme, increases noise-induced hearing loss in mice. Two-month-old "knockout" mice with a targeted inactivating mutation of the gene coding for glutathione peroxidase (Gpx1) and wild type controls were exposed to broadband noise for one hour at 110 dB SPL. Auditory brainstem response (ABR) thresholds at test frequencies ranging from 5 to 40 kHz were obtained two and four weeks after exposure to determine the stable permanent component of the hearing loss. Depending on test frequency, Gpx1 knockout mice showed up to 16 dB higher ABR thresholds prior to noise exposure, and up to 15 dB greater noise-induced hearing loss, compared with controls. Within the cochlear base, there was also a significant contribution of the knockout to inner and outer hair cell loss, as well as nerve fiber loss. Our results support a link between genetic impairment of antioxidant defenses, vulnerability of the cochlea injury, and cochlear degeneration. Such impairment produces characteristics expected of some mutations associated with age-related hearing loss and offers one possible mechanism for their action. PMID:11545230

  6. Apparent cooperativity of amino acid transport in Halobacterium halobium - Effect of electrical potential

    NASA Technical Reports Server (NTRS)

    Lanyi, J. K.

    1978-01-01

    Active serine accumulation in cell envelope vesicles from Halobacterium halobium proceeds by co-transport with Na(+) and can be induced by either transmembrane electrical potential or transmembrane Na(+) concentration difference. It was shown earlier that in the former case the initial transport rate is a fourth-power function of the magnitude of the electrochemical potential difference of sodium ions, and in the latter, a second-power function. A possible interpretation of this finding is cooperativity of sodium-transporting sites in the transport carrier. When both kinds of driving force are imposed simultaneously on the vesicles, fourth-power dependence on the total potential difference of sodium ions is obtained, suggesting that the transport carrier is regulated by the electrical potential. Heat treatment of the vesicles at 48 C partially inactivates transport and abolishes this effect of the electrical potential.

  7. Long noncoding RNA HOTTIP cooperates with CCCTC-binding factor to coordinate HOXA gene expression.

    PubMed

    Wang, Feng; Tang, Zhongqiong; Shao, Honglian; Guo, Jun; Tan, Tao; Dong, Yang; Lin, Lianbing

    2018-06-12

    The spatiotemporal control of HOX gene expression is dependent on positional identity and often correlated to their genomic location within each loci. Maintenance of HOX expression patterns is under complex transcriptional and epigenetic regulation, which is not well understood. Here we demonstrate that HOTTIP, a lincRNA transcribed from the 5' edge of the HOXA locus, physically associates with the CCCTC-binding factor (CTCF) that serves as an insulator by organizing HOXA cluster into disjoint domains, to cooperatively maintain the chromatin modifications of HOXA genes and thus coordinate the transcriptional activation of distal HOXA genes in human foreskin fibroblasts. Our results reveal the functional connection of HOTTIP and CTCF, and shed light on lincRNAs in gene activation and CTCF mediated chromatin organization. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. PIK3CA-mutated melanoma cells rely on cooperative signaling through mTORC1/2 for sustained proliferation.

    PubMed

    Silva, Jillian M; Deuker, Marian M; Baguley, Bruce C; McMahon, Martin

    2017-05-01

    Malignant conversion of BRAF- or NRAS-mutated melanocytes into melanoma cells can be promoted by PI3'-lipid signaling. However, the mechanism by which PI3'-lipid signaling cooperates with mutationally activated BRAF or NRAS has not been adequately explored. Using human NRAS- or BRAF-mutated melanoma cells that co-express mutationally activated PIK3CA, we explored the contribution of PI3'-lipid signaling to cell proliferation. Despite mutational activation of PIK3CA, melanoma cells were more sensitive to the biochemical and antiproliferative effects of broader spectrum PI3K inhibitors than to an α-selective PI3K inhibitor. Combined pharmacological inhibition of MEK1/2 and PI3K signaling elicited more potent antiproliferative effects and greater inhibition of the cell division cycle compared to single-agent inhibition of either pathway alone. Analysis of signaling downstream of MEK1/2 or PI3K revealed that these pathways cooperate to regulate cell proliferation through mTORC1-mediated effects on ribosomal protein S6 and 4E-BP1 phosphorylation in an AKT-dependent manner. Although PI3K inhibition resulted in cytostatic effects on xenografted NRAS Q61H /PIK3CA H1047R melanoma, combined inhibition of MEK1/2 plus PI3K elicited significant melanoma regression. This study provides insights as to how mutationally activated PIK3CA acts in concert with MEK1/2 signaling to cooperatively regulate mTORC1/2 to sustain PIK3CA-mutated melanoma proliferation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. 1 CFR 8.7 - Agency cooperation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 1 General Provisions 1 2011-01-01 2011-01-01 false Agency cooperation. 8.7 Section 8.7 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER SPECIAL EDITIONS OF THE FEDERAL REGISTER CODE OF FEDERAL REGULATIONS § 8.7 Agency cooperation. Each agency shall cooperate in keeping publication of the...

  10. 1 CFR 8.7 - Agency cooperation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Agency cooperation. 8.7 Section 8.7 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER SPECIAL EDITIONS OF THE FEDERAL REGISTER CODE OF FEDERAL REGULATIONS § 8.7 Agency cooperation. Each agency shall cooperate in keeping publication of the...

  11. 24 CFR 213.275 - Nature of the Cooperative Management Housing Insurance Fund.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Nature of the Cooperative Management Housing Insurance Fund. 213.275 Section 213.275 Housing and Urban Development Regulations Relating... Nature of the Cooperative Management Housing Insurance Fund. The Cooperative Management Housing Insurance...

  12. 30 CFR 900.15 - Federal lands program cooperative agreements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... INTRODUCTION § 900.15 Federal lands program cooperative agreements. The full text of any State and Federal cooperative agreement for the regulation of coal exploration and mining on Federal lands is published below... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Federal lands program cooperative agreements...

  13. 30 CFR 900.15 - Federal lands program cooperative agreements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... INTRODUCTION § 900.15 Federal lands program cooperative agreements. The full text of any State and Federal cooperative agreement for the regulation of coal exploration and mining on Federal lands is published below... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Federal lands program cooperative agreements...

  14. 30 CFR 900.15 - Federal lands program cooperative agreements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... INTRODUCTION § 900.15 Federal lands program cooperative agreements. The full text of any State and Federal cooperative agreement for the regulation of coal exploration and mining on Federal lands is published below... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Federal lands program cooperative agreements...

  15. 30 CFR 900.15 - Federal lands program cooperative agreements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... INTRODUCTION § 900.15 Federal lands program cooperative agreements. The full text of any State and Federal cooperative agreement for the regulation of coal exploration and mining on Federal lands is published below... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Federal lands program cooperative agreements...

  16. 77 FR 17353 - Federal Acquisition Regulation; New Designated Country (Armenia) and Other Trade Agreements Updates

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-26

    ...) 52.222-19, Child Labor--Cooperation with Authorities and Remedies (MAR 2012) (E.O. 13126...) * * * (1) * * * (i) 52.222-19, Child Labor--Cooperation with Authorities and Remedies (MAR 2012) (E.O... Labor--Cooperation with Authorities and Remedies. * * * * * CHILD LABOR--COOPERATION WITH AUTHORITIES...

  17. 7 CFR 989.115 - Independent handler, major cooperative marketing association handler, and small cooperative...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Independent handler, major cooperative marketing association handler, and small cooperative marketing association handler. 989.115 Section 989.115 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables,...

  18. 24 CFR 213.275 - Nature of the Cooperative Management Housing Insurance Fund.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Nature of the Cooperative Management Housing Insurance Fund. 213.275 Section 213.275 Housing and Urban Development Regulations Relating... Nature of the Cooperative Management Housing Insurance Fund. The Cooperative Management Housing Insurance...

  19. 24 CFR 213.275 - Nature of the Cooperative Management Housing Insurance Fund.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Nature of the Cooperative Management Housing Insurance Fund. 213.275 Section 213.275 Housing and Urban Development Regulations Relating... Nature of the Cooperative Management Housing Insurance Fund. The Cooperative Management Housing Insurance...

  20. 24 CFR 213.275 - Nature of the Cooperative Management Housing Insurance Fund.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Nature of the Cooperative Management Housing Insurance Fund. 213.275 Section 213.275 Housing and Urban Development Regulations Relating... Nature of the Cooperative Management Housing Insurance Fund. The Cooperative Management Housing Insurance...

  1. 24 CFR 213.275 - Nature of the Cooperative Management Housing Insurance Fund.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Nature of the Cooperative Management Housing Insurance Fund. 213.275 Section 213.275 Housing and Urban Development Regulations Relating... Nature of the Cooperative Management Housing Insurance Fund. The Cooperative Management Housing Insurance...

  2. 1 CFR 8.7 - Agency cooperation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 1 General Provisions 1 2013-01-01 2012-01-01 true Agency cooperation. 8.7 Section 8.7 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER SPECIAL EDITIONS OF THE FEDERAL REGISTER CODE OF FEDERAL REGULATIONS § 8.7 Agency cooperation. Each agency shall cooperate in keeping publication of the...

  3. 1 CFR 8.7 - Agency cooperation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 1 General Provisions 1 2012-01-01 2012-01-01 false Agency cooperation. 8.7 Section 8.7 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER SPECIAL EDITIONS OF THE FEDERAL REGISTER CODE OF FEDERAL REGULATIONS § 8.7 Agency cooperation. Each agency shall cooperate in keeping publication of the...

  4. 1 CFR 8.7 - Agency cooperation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 1 General Provisions 1 2014-01-01 2012-01-01 true Agency cooperation. 8.7 Section 8.7 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER SPECIAL EDITIONS OF THE FEDERAL REGISTER CODE OF FEDERAL REGULATIONS § 8.7 Agency cooperation. Each agency shall cooperate in keeping publication of the...

  5. On the mechanism for PPAR agonists to enhance ABCA1 gene expression

    PubMed Central

    Ogata, Masaki; Tsujita, Maki; Hossain, Mohammad Anwar; Akita, Nobukatsu; Gonzalez, Frank J.; Staels, Bart; Suzuki, Shogo; Fukutomi, Tatsuya; Kimura, Genjiro; Yokoyama, Shinji

    2009-01-01

    Expression of ATP binding cassette transporter A1 (ABCA1), a major regulator of high density lipoprotein (HDL) biogenesis, is known to be up-regulated by the transcription factor liver X receptor (LXR) α, and expression is further enhanced by activation of the peroxisome proliferator activated receptors (PPARs). We investigated this complex regulatory network using specific PPAR agonists: four fibrates (fenofibrate, bezafibrate, gemfibrozil and LY518674), a PPAR δ agonist (GW501516) and a PPAR γ agonist (pioglitazone). All of these compounds increased the expression of LXRs, PPARs and ABCA1 mRNAs, and associated apoA-I-mediated lipid release in THP-1 macrophage, WI38 fibroblast and mouse fibroblast. When mouse fibroblasts lacking expression of PPAR α were examined, the effects of fenofibrate and LY518674 were markedly diminished while induction by other ligands were retained. The PPAR α promoter was activated by all of these compounds in an LXR α-dependent manner, and partially in a PPAR α-dependent manner, in mouse fibroblast. The LXR responsive element (LXRE)-luciferase activity was enhanced by all the compounds in an LXR α-dependent manner in mouse fibroblast. This activation was exclusively PPAR α-dependent by fenofibrate and LY518674, but nonexclusively by the others. We conclude that PPARs and LXRs are involved in the regulation of ABCA1 expression and HDL biogenesis in a cooperative signal transduction pathway. PMID:19201410

  6. 29 CFR 501.21 - Failure to cooperate with investigations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Failure to cooperate with investigations. 501.21 Section 501.21 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS ENFORCEMENT OF CONTRACTUAL OBLIGATIONS FOR TEMPORARY ALIEN AGRICULTURAL WORKERS ADMITTED UNDER...

  7. 29 CFR 501.7 - Cooperation with Federal officials.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Cooperation with Federal officials. 501.7 Section 501.7 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS ENFORCEMENT OF CONTRACTUAL OBLIGATIONS FOR TEMPORARY ALIEN AGRICULTURAL WORKERS ADMITTED UNDER SECTION 218 OF...

  8. The apelin receptor inhibits the angiotensin II type 1 receptor via allosteric trans-inhibition

    PubMed Central

    Siddiquee, K; Hampton, J; McAnally, D; May, LT; Smith, LH

    2013-01-01

    Background and Purpose The apelin receptor (APJ) is often co-expressed with the angiotensin II type-1 receptor (AT1) and acts as an endogenous counter-regulator. Apelin antagonizes Ang II signalling, but the precise molecular mechanism has not been elucidated. Understanding this interaction may lead to new therapies for the treatment of cardiovascular disease. Experimental Approach The physical interaction of APJ and AT1 receptors was detected by co-immunoprecipitation and bioluminescence resonance energy transfer (BRET). Functional and pharmacological interactions were measured by G-protein-dependent signalling and recruitment of β-arrestin. Allosterism and cooperativity between APJ and AT1 were measured by radioligand binding assays. Key Results Apelin, but not Ang II, induced APJ : AT1 heterodimerization forced AT1 into a low-affinity state, reducing Ang II binding. Likewise, apelin mediated a concentration-dependent depression in the maximal production of inositol phosphate (IP1) and β-arrestin recruitment to AT1 in response to Ang II. The signal depression approached a limit, the magnitude of which was governed by the cooperativity indicative of a negative allosteric interaction. Fitting the data to an operational model of allosterism revealed that apelin-mediated heterodimerization significantly reduces Ang II signalling efficacy. These effects were not observed in the absence of apelin. Conclusions and Implications Apelin-dependent heterodimerization between APJ and AT1 causes negative allosteric regulation of AT1 function. As AT1 is significant in the pathogenesis of cardiovascular disease, these findings suggest that impaired apelin and APJ function may be a common underlying aetiology. Linked Article This article is commented on by Goupil et al., pp. 1101–1103 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12040 PMID:22935142

  9. FLASH is essential during early embryogenesis and cooperates with p73 to regulate histone gene transcription.

    PubMed

    De Cola, A; Bongiorno-Borbone, L; Bianchi, E; Barcaroli, D; Carletti, E; Knight, R A; Di Ilio, C; Melino, G; Sette, C; De Laurenzi, V

    2012-02-02

    Replication-dependent histone gene expression is a fundamental process occurring in S-phase under the control of the cyclin-E/CDK2 complex. This process is regulated by a number of proteins, including Flice-Associated Huge Protein (FLASH) (CASP8AP2), concentrated in specific nuclear organelles known as HLBs. FLASH regulates both histone gene transcription and mRNA maturation, and its downregulation in vitro results in the depletion of the histone pull and cell-cycle arrest in S-phase. Here we show that the transcription factor p73 binds to FLASH and is part of the complex that regulates histone gene transcription. Moreover, we created a novel gene trap to disrupt FLASH in mice, and we show that homozygous deletion of FLASH results in early embryonic lethality, owing to arrest of FLASH(-/-) embryos at the morula stage. These results indicate that FLASH is an essential, non-redundant regulator of histone transcription and cell cycle during embryogenesis.

  10. Threshold-dependent cooperativity of Pdx1 and Oc1 in pancreatic progenitors establishes competency for endocrine differentiation and β-cell function

    PubMed Central

    Wright, Christopher V.E.; Won, Kyoung-Jae

    2016-01-01

    Summary Pdx1 and Oc1 are co-expressed in multipotent pancreatic progenitors and regulate the pro-endocrine gene Neurog3. Their expression diverges in later organogenesis, with Oc1 absent from hormone+ cells and Pdx1 maintained in mature β cells. In a classical genetic test for cooperative functional interactions, we derived mice with combined Pdx1 and Oc1 heterozygosity. Endocrine development in double-heterozygous pancreata was normal at embryonic day (e)13.5, but defects in specification and differentiation were apparent at e15.5, the height of the second wave of differentiation. Pancreata from double heterozygotes showed alterations in the expression of genes crucial for β-cell development and function, decreased numbers and altered allocation of Neurog3-expressing endocrine progenitors, and defective endocrine differentiation. Defects in islet gene expression and β-cell function persisted in double heterozygous neonates. These results suggest that Oc1 and Pdx1 cooperate prior to their divergence, in pancreatic progenitors, to allow for proper differentiation and functional maturation of β cells. PMID:27292642

  11. 29 CFR 502.6 - Cooperation with DOL officials.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Cooperation with DOL officials. 502.6 Section 502.6 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS ENFORCEMENT OF CONTRACTUAL OBLIGATIONS FOR TEMPORARY ALIEN AGRICULTURAL WORKERS ADMITTED UNDER SECTION 218 OF THE...

  12. 7 CFR 75.4 - Federal and State cooperation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Federal and State cooperation. 75.4 Section 75.4 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 194...

  13. 7 CFR 75.4 - Federal and State cooperation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Federal and State cooperation. 75.4 Section 75.4 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 194...

  14. 7 CFR 75.4 - Federal and State cooperation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Federal and State cooperation. 75.4 Section 75.4 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 194...

  15. 7 CFR 75.4 - Federal and State cooperation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Federal and State cooperation. 75.4 Section 75.4 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 194...

  16. 7 CFR 75.4 - Federal and State cooperation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Federal and State cooperation. 75.4 Section 75.4 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 194...

  17. 48 CFR 352.222-70 - Contractor cooperation in equal employment opportunity investigations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Contractor cooperation in... Regulations System HEALTH AND HUMAN SERVICES CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES... Agency management, Agency EEO officials, the Equal Employment Opportunity Commission (EEOC), or a court...

  18. 48 CFR 352.222-70 - Contractor cooperation in equal employment opportunity investigations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Contractor cooperation in... Regulations System HEALTH AND HUMAN SERVICES CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES... Agency management, Agency EEO officials, the Equal Employment Opportunity Commission (EEOC), or a court...

  19. 48 CFR 352.222-70 - Contractor cooperation in equal employment opportunity investigations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Contractor cooperation in... Regulations System HEALTH AND HUMAN SERVICES CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES... Agency management, Agency EEO officials, the Equal Employment Opportunity Commission (EEOC), or a court...

  20. 48 CFR 352.222-70 - Contractor cooperation in equal employment opportunity investigations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Contractor cooperation in... Regulations System HEALTH AND HUMAN SERVICES CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES... Agency management, Agency EEO officials, the Equal Employment Opportunity Commission (EEOC), or a court...

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