Sample records for accessory proteins regulate

  1. Accessory proteins of SARS-CoV and other coronaviruses.

    PubMed

    Liu, Ding Xiang; Fung, To Sing; Chong, Kelvin Kian-Long; Shukla, Aditi; Hilgenfeld, Rolf

    2014-09-01

    The huge RNA genome of SARS coronavirus comprises a number of open reading frames that code for a total of eight accessory proteins. Although none of these are essential for virus replication, some appear to have a role in virus pathogenesis. Notably, some SARS-CoV accessory proteins have been shown to modulate the interferon signaling pathways and the production of pro-inflammatory cytokines. The structural information on these proteins is also limited, with only two (p7a and p9b) having their structures determined by X-ray crystallography. This review makes an attempt to summarize the published knowledge on SARS-CoV accessory proteins, with an emphasis on their involvement in virus-host interaction. The accessory proteins of other coronaviruses are also briefly discussed. This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses" (see Introduction by Hilgenfeld and Peiris (2013)). Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Wongabel rhabdovirus accessory protein U3 targets the SWI/SNF chromatin remodeling complex.

    PubMed

    Joubert, D Albert; Rodriguez-Andres, Julio; Monaghan, Paul; Cummins, Michelle; McKinstry, William J; Paradkar, Prasad N; Moseley, Gregory W; Walker, Peter J

    2015-01-15

    Wongabel virus (WONV) is an arthropod-borne rhabdovirus that infects birds. It is one of the growing array of rhabdoviruses with complex genomes that encode multiple accessory proteins of unknown function. In addition to the five canonical rhabdovirus structural protein genes (N, P, M, G, and L), the 13.2-kb negative-sense single-stranded RNA (ssRNA) WONV genome contains five uncharacterized accessory genes, one overlapping the N gene (Nx or U4), three located between the P and M genes (U1 to U3), and a fifth one overlapping the G gene (Gx or U5). Here we show that WONV U3 is expressed during infection in insect and mammalian cells and is required for efficient viral replication. A yeast two-hybrid screen against a mosquito cell cDNA library identified that WONV U3 interacts with the 83-amino-acid (aa) C-terminal domain of SNF5, a component of the SWI/SNF chromatin remodeling complex. The interaction was confirmed by affinity chromatography, and nuclear colocalization was established by confocal microscopy. Gene expression studies showed that SNF5 transcripts are upregulated during infection of mosquito cells with WONV, as well as West Nile virus (Flaviviridae) and bovine ephemeral fever virus (Rhabdoviridae), and that SNF5 knockdown results in increased WONV replication. WONV U3 also inhibits SNF5-regulated expression of the cytokine gene CSF1. The data suggest that WONV U3 targets the SWI/SNF complex to block the host response to infection. The rhabdoviruses comprise a large family of RNA viruses infecting plants, vertebrates, and invertebrates. In addition to the major structural proteins (N, P, M, G, and L), many rhabdoviruses encode a diverse array of accessory proteins of largely unknown function. Understanding the role of these proteins may reveal much about host-pathogen interactions in infected cells. Here we examine accessory protein U3 of Wongabel virus, an arthropod-borne rhabdovirus that infects birds. We show that U3 enters the nucleus and interacts

  3. Wongabel Rhabdovirus Accessory Protein U3 Targets the SWI/SNF Chromatin Remodeling Complex

    PubMed Central

    Joubert, D. Albert; Rodriguez-Andres, Julio; Monaghan, Paul; Cummins, Michelle; McKinstry, William J.; Paradkar, Prasad N.; Moseley, Gregory W.

    2014-01-01

    ABSTRACT Wongabel virus (WONV) is an arthropod-borne rhabdovirus that infects birds. It is one of the growing array of rhabdoviruses with complex genomes that encode multiple accessory proteins of unknown function. In addition to the five canonical rhabdovirus structural protein genes (N, P, M, G, and L), the 13.2-kb negative-sense single-stranded RNA (ssRNA) WONV genome contains five uncharacterized accessory genes, one overlapping the N gene (Nx or U4), three located between the P and M genes (U1 to U3), and a fifth one overlapping the G gene (Gx or U5). Here we show that WONV U3 is expressed during infection in insect and mammalian cells and is required for efficient viral replication. A yeast two-hybrid screen against a mosquito cell cDNA library identified that WONV U3 interacts with the 83-amino-acid (aa) C-terminal domain of SNF5, a component of the SWI/SNF chromatin remodeling complex. The interaction was confirmed by affinity chromatography, and nuclear colocalization was established by confocal microscopy. Gene expression studies showed that SNF5 transcripts are upregulated during infection of mosquito cells with WONV, as well as West Nile virus (Flaviviridae) and bovine ephemeral fever virus (Rhabdoviridae), and that SNF5 knockdown results in increased WONV replication. WONV U3 also inhibits SNF5-regulated expression of the cytokine gene CSF1. The data suggest that WONV U3 targets the SWI/SNF complex to block the host response to infection. IMPORTANCE The rhabdoviruses comprise a large family of RNA viruses infecting plants, vertebrates, and invertebrates. In addition to the major structural proteins (N, P, M, G, and L), many rhabdoviruses encode a diverse array of accessory proteins of largely unknown function. Understanding the role of these proteins may reveal much about host-pathogen interactions in infected cells. Here we examine accessory protein U3 of Wongabel virus, an arthropod-borne rhabdovirus that infects birds. We show that U3 enters the

  4. Proteomic identification of Drosophila melanogaster male accessory gland proteins, including a pro-cathepsin and a soluble gamma-glutamyl transpeptidase.

    PubMed

    Walker, Michael J; Rylett, Caroline M; Keen, Jeff N; Audsley, Neil; Sajid, Mohammed; Shirras, Alan D; Isaac, R Elwyn

    2006-05-02

    In Drosophila melanogaster, the male seminal fluid contains proteins that are important for reproductive success. Many of these proteins are synthesised by the male accessory glands and are secreted into the accessory gland lumen, where they are stored until required. Previous studies on the identification of Drosophila accessory gland products have largely focused on characterisation of male-specific accessory gland cDNAs from D. melanogaster and, more recently, Drosophila simulans. In the present study, we have used a proteomics approach without any sex bias to identify proteins in D. melanogaster accessory gland secretions. Thirteen secreted accessory gland proteins, including seven new accessory gland proteins, were identified by 2D-gel electrophoresis combined with mass spectrometry of tryptic fragments. They included protein-folding and stress-response proteins, a hormone, a lipase, a serpin, a cysteine-rich protein and two peptidases, a pro-enzyme form of a cathepsin K-like cysteine peptidase and a gamma-glutamyl transpeptidase. Enzymatic studies established that accessory gland secretions contain a cysteine peptidase zymogen that can be activated at low pH. This peptidase may have a role in the processing of female and other male-derived proteins, but is unlikely to be involved in the processing of the sex peptide. gamma-Glutamyl transpeptidases are type II integral membrane proteins; however, the identified AG gamma-glutamyl transpeptidase (GGT-1) is unusual in that it is predicted to be a soluble secreted protein, a prediction that is supported by biochemical evidence. GGT-1 is possibly involved in maintaining a protective redox environment for sperm. The strong gamma-glutamyl transpeptidase activity found in the secretions provides an explanation for the observation that glutamic acid is the most abundant free amino acid in accessory gland secretions of D. melanogaster. We have applied biochemical approaches, not used previously, to characterise

  5. Clathrin- and AP-2-binding sites in HIP1 uncover a general assembly role for endocytic accessory proteins.

    PubMed

    Mishra, S K; Agostinelli, N R; Brett, T J; Mizukami, I; Ross, T S; Traub, L M

    2001-12-07

    Clathrin-mediated endocytosis is a major pathway for the internalization of macromolecules into the cytoplasm of eukaryotic cells. The principle coat components, clathrin and the AP-2 adaptor complex, assemble a polyhedral lattice at plasma membrane bud sites with the aid of several endocytic accessory proteins. Here, we show that huntingtin-interacting protein 1 (HIP1), a binding partner of huntingtin, copurifies with brain clathrin-coated vesicles and associates directly with both AP-2 and clathrin. The discrete interaction sequences within HIP1 that facilitate binding are analogous to motifs present in other accessory proteins, including AP180, amphiphysin, and epsin. Bound to a phosphoinositide-containing membrane surface via an epsin N-terminal homology (ENTH) domain, HIP1 associates with AP-2 to provide coincident clathrin-binding sites that together efficiently recruit clathrin to the bilayer. Our data implicate HIP1 in endocytosis, and the similar modular architecture and function of HIP1, epsin, and AP180 suggest a common role in lipid-regulated clathrin lattice biogenesis.

  6. Role of Accessory Proteins of HTLV-1 in Viral Replication, T Cell Activation, and Cellular Gene Expression

    PubMed Central

    Michael, Bindhu; Nair, Amithraj; Lairmore, Michael D.

    2010-01-01

    Human T-cell lymphotropic virus type 1 (HTLV-1), causes adult T cell leukemia/lymphoma (ATLL), and initiates a variety of immune mediated disorders. The viral genome encodes common structural and enzymatic proteins characteristic of all retroviruses and utilizes alternative splicing and alternate codon usage to make several regulatory and accessory proteins encoded in the pX region (pX ORF I to IV). Recent studies indicate that the accessory proteins p12I, p27I, p13II, and p30II, encoded by pX ORF I and II, contribute to viral replication and the ability of the virus to maintain typical in vivo expression levels. Proviral clones that are mutated in either pX ORF I or II, while fully competent in cell culture, are severely limited in their replicative capacity in a rabbit model. These HTLV-1 accessory proteins are critical for establishment of viral infectivity, enhance T- lymphocyte activation and potentially alter gene transcription and mitochondrial function. HTLV-1 pX ORF I expression is critical to the viral infectivity in resting primary lymphocytes suggesting a role for the calcineurin-binding protein p12I in lymphocyte activation. The endoplasmic reticulum and cis-Golgi localizing p12I activates NFAT, a key T cell transcription factor, through calcium-mediated signaling pathways and may lower the threshold of lymphocyte activation via the JAK/STAT pathway. In contrast p30II localizes to the nucleus and represses viral promoter activity, but may regulate cellular gene expression through p300/CBP or related co-activators of transcription. The mitochondrial localizing p13II induces morphologic changes in the organelle and may influence energy metabolism infected cells. Future studies of the molecular details HTLV-1 “accessory” proteins interactions will provide important new directions for investigations of HTLV-1 and related viruses associated with lymphoproliferative diseases. Thus, the accessory proteins of HTLV-1, once thought to be dispensable for

  7. Accessory replicative helicases and the replication of protein-bound DNA.

    PubMed

    Brüning, Jan-Gert; Howard, Jamieson L; McGlynn, Peter

    2014-12-12

    Complete, accurate duplication of the genetic material is a prerequisite for successful cell division. Achieving this accuracy is challenging since there are many barriers to replication forks that may cause failure to complete genome duplication or result in possibly catastrophic corruption of the genetic code. One of the most important types of replicative barriers are proteins bound to the template DNA, especially transcription complexes. Removal of these barriers demands energy input not only to separate the DNA strands but also to disrupt multiple bonds between the protein and DNA. Replicative helicases that unwind the template DNA for polymerases at the fork can displace proteins bound to the template. However, even occasional failures in protein displacement by the replicative helicase could spell disaster. In such circumstances, failure to restart replication could result in incomplete genome duplication. Avoiding incomplete genome duplication via the repair and restart of blocked replication forks also challenges viability since the involvement of recombination enzymes is associated with the risk of genome rearrangements. Organisms have therefore evolved accessory replicative helicases that aid replication fork movement along protein-bound DNA. These helicases reduce the dangers associated with replication blockage by protein-DNA complexes, aiding clearance of blocks and resumption of replication by the same replisome thus circumventing the need for replication repair and restart. This review summarises recent work in bacteria and eukaryotes that has begun to delineate features of accessory replicative helicases and their importance in genome stability. Copyright © 2014. Published by Elsevier Ltd.

  8. Porcine deltacoronavirus accessory protein NS6 antagonizes IFN-β production by interfering with the binding of RIG-I/MDA5 to double-stranded RNA.

    PubMed

    Fang, Puxian; Fang, Liurong; Ren, Jie; Hong, Yingying; Liu, Xiaorong; Zhao, Yunyang; Wang, Dang; Peng, Guiqing; Xiao, Shaobo

    2018-05-16

    Porcine deltacoronavirus (PDCoV) has recently emerged as an enteric pathogen that can cause serious vomiting and diarrhea in suckling piglets. The first outbreak of PDCoV occurred in the United States in 2014 and was followed by reports of PDCoV in South Korea, China, Thailand, Lao people's Democratic Republic, and Vietnam, leading to economic losses for pig farms and posing considerable threat to the swine industry worldwide. Our previous studies have shown that PDCoV encodes three accessory proteins, NS6, NS7, and NS7a, but the functions of these proteins in viral replication, pathogenesis, and immune regulation remain unclear. Here, we found that ectopic expression of accessory protein NS6 significantly inhibits Sendai virus-induced interferon-β (IFN-β) production, as well as the activation of transcription factors IRF3 and NF-κB. Interestingly, NS6 does not impede the IFN-β promoter activation mediated via key molecules in the RIG-I-like receptor (RLR) signaling pathway, specifically RIG-I, MDA5, and their downstream molecules MAVS, TBK1, IKKϵ, and IRF3. Further analyses revealed that NS6 is not a RNA-binding protein; however, it interacts with RIG-I/MDA5. This interaction attenuates the binding of double-stranded RNA by RIG-I/MDA5, resulting in the reduction of RLR-mediated IFN-β production. Taken together, our results demonstrate that ectopic expression of NS6 antagonizes IFN-β production by interfering with the binding of RIG-I/MDA5 to double-stranded RNA, revealing a new strategy employed by PDCoV accessory proteins to counteract the host innate antiviral immune response. IMPORTANCE Coronavirus accessory proteins are species-specific, and they perform multiple functions in viral pathogenicity and immunity, such as acting as interferon (IFN) antagonists and cell death inducers. Our previous studies have shown that porcine deltacoronavirus (PDCoV) encodes three accessory proteins. Here, we demonstrated for the first time that PDCoV accessory protein NS

  9. Functional characterisation of a TLR accessory protein, UNC93B1, in Atlantic salmon (Salmo salar).

    PubMed

    Lee, P T; Zou, J; Holland, J W; Martin, S A M; Scott, C J W; Kanellos, T; Secombes, C J

    2015-05-01

    Toll-like receptors (TLRs) are indispensable components of the innate immune system, which recognise conserved pathogen associated molecular patterns (PAMPs) and induce a series of defensive immune responses to protect the host. Biosynthesis, localisation and activation of TLRs are dependent on TLR accessory proteins. In this study, we identified the accessory protein, UNC93B1, from Atlantic salmon (Salmo salar) whole-genome shotgun (WGS) contigs aided by the conserved gene synteny of genes flanking UNC93B1 in fish, birds and mammals. Phylogenetic analysis showed that salmon UNC93B1 grouped with other vertebrate UNC93B1 molecules, and had highest amino acid identity and similarity to zebrafish UNC93B1. The salmon UNC93B1 gene organisation was also similar in structure to mammalian UNC93B1. Our gene expression studies revealed that salmon UNC93B1 was more highly expressed in spleen, liver and gill tissues but was expressed at a lower level in head kidney tissue in post-smolts relative to parr. Moreover, salmon UNC93B1 mRNA transcripts were up-regulated in vivo in spleen tissue from polyI:C treated salmon and in vitro in polyI:C or IFNγ stimulated Salmon Head Kidney-1 (SHK-1) cells. Initial studies into the functional role of salmon UNC93B1 in fish TLR signalling found that both wild type salmon UNC93B1 and a molecule with a site-directed mutation (H424R) co-immunoprecipitated with salmon TLR19, TLR20a and TLR20d. Overall, these data illustrate the potential importance of UNC93B1 as an accessory protein in fish TLR signalling. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. The family B1 GPCR: structural aspects and interaction with accessory proteins.

    PubMed

    Couvineau, Alain; Laburthe, Marc

    2012-01-01

    G protein coupled receptors (GPCRs) play a crucial role in physiology and pathophysiology in humans. Beside the large family A (rhodopsin-like receptors) and family C GPCR (metabotropic glutamate receptors), the small family B1 GPCR (secretin-like receptors) includes important receptors such as vasoactive intestinal peptide receptors (VPAC), pituitary adenylyl cyclase activating peptide receptor (PAC1R), secretin receptor (SECR), growth hormone releasing factor receptor (GRFR), glucagon receptor (GCGR), glucagon like-peptide 1 and 2 receptors (GLPR), gastric inhibitory peptide receptor (GIPR), parathyroid hormone receptors (PTHR), calcitonin receptors (CTR) and corticotropin-releasing factor receptors (CRFR). They represent very promising targets for the development of drugs having therapeutical impact on many diseases such as chronic inflammation, neurodegeneration, diabetes, stress and osteoporosis. Over the past decade, structure-function relationship studies have demonstrated that the N-terminal ectodomain (N-ted) of family B1 receptors plays a pivotal role in natural ligand recognition. Structural analysis of some family B1 GPCR N-teds revealed the existence of a Sushi domain fold consisting of two antiparallel β sheets stabilized by three disulfide bonds and a salt bridge. The family B1 GPCRs promote cellular responses through a signaling pathway including predominantly the Gsadenylyl cyclase-cAMP pathway activation. Family B1 GPCRs also interact with a few accessory proteins which play a role in cell signaling, receptor expression and/or pharmacological profiles of receptors. These accessory proteins may represent new targets for the design of new drugs. Here, we review the current knowledge regarding: i) the structure of family B1 GPCR binding domain for natural ligands and ii) the interaction of family B1 GPCRs with accessory proteins.

  11. Protein Tunnels: The Case of Urease Accessory Proteins.

    PubMed

    Musiani, Francesco; Gioia, Dario; Masetti, Matteo; Falchi, Federico; Cavalli, Andrea; Recanatini, Maurizio; Ciurli, Stefano

    2017-05-09

    Transition metals are both essential micronutrients and limited in environmental availability. The Ni(II)-dependent urease protein, the most efficient enzyme known to date, is a paradigm for studying the strategies that cells use to handle an essential, yet toxic, metal ion. Urease is a virulence factor of several human pathogens, in addition to decreasing the efficiency of soil organic nitrogen fertilization. Ni(II) insertion in the urease active site is performed through the action of three essential accessory proteins: UreD, UreF, and UreG. The crystal structure of the UreD-UreF-UreG complex from the human pathogen Helicobacter pylori (HpUreDFG) revealed the presence of tunnels that cross the entire length of both UreF and UreD, potentially able to deliver Ni(II) ions from UreG to apo-urease. Atomistic molecular dynamics simulations performed on the HpUreDFG complex in explicit solvent and at physiological ionic conditions demonstrate the stability of these protein tunnels in solution and provide insights on the trafficking of water molecules inside the tunnels. The presence of different alternative routes across the identified tunnels for Ni(II) ions, water molecules, and carbonate ions, all involved in urease activation, is highlighted here, and their potential role in the urease activation mechanism is discussed.

  12. Vibrio azureus emits blue-shifted light via an accessory blue fluorescent protein.

    PubMed

    Yoshizawa, Susumu; Karatani, Hajime; Wada, Minoru; Kogure, Kazuhiro

    2012-04-01

    Luminous marine bacteria usually emit bluish-green light with a peak emission wavelength (λ(max) ) at about 490 nm. Some species belonging to the genus Photobacterium are exceptions, producing an accessory blue fluorescent protein (lumazine protein: LumP) that causes a blue shift, from λ(max)  ≈ 490 to λ(max)  ≈ 476 nm. However, the incidence of blue-shifted light emission or the presence of accessory fluorescent proteins in bacteria of the genus Vibrio has never been reported. From our spectral analysis of light emitted by 16 luminous strains of the genus Vibrio, it was revealed that most strains of Vibrio azureus emit a blue-shifted light with a peak at approximately 472 nm, whereas other Vibrio strains emit light with a peak at around 482 nm. Therefore, we investigated the mechanism underlying this blue shift in V. azureus NBRC 104587(T) . Here, we describe the blue-shifted light emission spectra and the isolation of a blue fluorescent protein. Intracellular protein analyses showed that this strain had a blue fluorescent protein (that we termed VA-BFP), the fluorescent spectrum of which was almost identical to that of the in vivo light emission spectrum of the strain. This result strongly suggested that VA-BFP was responsible for the blue-shifted light emission of V. azureus. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  13. Molecular determinants for recognition of divergent SAMHD1 proteins by the lentiviral accessory protein Vpx.

    PubMed

    Schwefel, David; Boucherit, Virginie C; Christodoulou, Evangelos; Walker, Philip A; Stoye, Jonathan P; Bishop, Kate N; Taylor, Ian A

    2015-04-08

    The SAMHD1 triphosphohydrolase inhibits HIV-1 infection of myeloid and resting T cells by depleting dNTPs. To overcome SAMHD1, HIV-2 and some SIVs encode either of two lineages of the accessory protein Vpx that bind the SAMHD1 N or C terminus and redirect the host cullin-4 ubiquitin ligase to target SAMHD1 for proteasomal degradation. We present the ternary complex of Vpx from SIV that infects mandrills (SIVmnd-2) with the cullin-4 substrate receptor, DCAF1, and N-terminal and SAM domains from mandrill SAMHD1. The structure reveals details of Vpx lineage-specific targeting of SAMHD1 N-terminal "degron" sequences. Comparison with Vpx from SIV that infects sooty mangabeys (SIVsmm) complexed with SAMHD1-DCAF1 identifies molecular determinants directing Vpx lineages to N- or C-terminal SAMHD1 sequences. Inspection of the Vpx-DCAF1 interface also reveals conservation of Vpx with the evolutionally related HIV-1/SIV accessory protein Vpr. These data suggest a unified model for how Vpx and Vpr exploit DCAF1 to promote viral replication. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  14. The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis

    PubMed Central

    McBride, Ruth; Fielding, Burtram C.

    2012-01-01

    A respiratory disease caused by a novel coronavirus, termed the severe acute respiratory syndrome coronavirus (SARS-CoV), was first reported in China in late 2002. The subsequent efficient human-to-human transmission of this virus eventually affected more than 30 countries worldwide, resulting in a mortality rate of ~10% of infected individuals. The spread of the virus was ultimately controlled by isolation of infected individuals and there has been no infections reported since April 2004. However, the natural reservoir of the virus was never identified and it is not known if this virus will re-emerge and, therefore, research on this virus continues. The SARS-CoV genome is about 30 kb in length and is predicted to contain 14 functional open reading frames (ORFs). The genome encodes for proteins that are homologous to known coronavirus proteins, such as the replicase proteins (ORFs 1a and 1b) and the four major structural proteins: nucleocapsid (N), spike (S), membrane (M) and envelope (E). SARS-CoV also encodes for eight unique proteins, called accessory proteins, with no known homologues. This review will summarize the current knowledge on SARS-CoV accessory proteins and will include: (i) expression and processing; (ii) the effects on cellular processes; and (iii) functional studies. PMID:23202509

  15. Transcriptional activation of melanocortin 2 receptor accessory protein by PPARγ in adipocytes

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

    Kim, Nam Soo; Kim, Yoon-Jin; Cho, Si Young

    2013-09-27

    Highlights: •MRAP enhanced HSL expression. •ACTH-mediated MRAP reduced glycerol release. •PPARγ induced MRAP expression. •PPARγ bound to the MRAP promoter. -- Abstract: Adrenocorticotropic hormone (ACTH) in rodents decreases lipid accumulation and body weight. Melanocortin receptor 2 (MC2R) and MC2R accessory protein (MRAP) are specific receptors for ACTH in adipocytes. Peroxisome proliferator-activated receptor γ (PPARγ) plays a role in the transcriptional regulation of metabolic pathways such as adipogenesis and β-oxidation of fatty acids. In this study we investigated the transcriptional regulation of MRAP expression during differentiation of 3T3-L1 cells. Stimulation with ACTH affected lipolysis in murine mature adipocytes via MRAP. Putativemore » peroxisome proliferator response element (PPRE) was identified in the MRAP promoter region. In chromatin immunoprecipitation and reporter assays, we observed binding of PPARγ to the MRAP promoter. The mutagenesis experiments showed that the −1209/−1198 region of the MRAP promoter could function as a PPRE site. These results suggest that PPARγ is required for transcriptional activation of the MRAP gene during adipogenesis, which contributes to understanding of the molecular mechanism of lipolysis in adipocytes.« less

  16. Comprehensive search for accessory proteins encoded with archaeal and bacterial type III CRISPR-cas gene cassettes reveals 39 new cas gene families.

    PubMed

    Shah, Shiraz A; Alkhnbashi, Omer S; Behler, Juliane; Han, Wenyuan; She, Qunxin; Hess, Wolfgang R; Garrett, Roger A; Backofen, Rolf

    2018-06-19

    A study was undertaken to identify conserved proteins that are encoded adjacent to cas gene cassettes of Type III CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats - CRISPR associated) interference modules. Type III modules have been shown to target and degrade dsDNA, ssDNA and ssRNA and are frequently intertwined with cofunctional accessory genes, including genes encoding CRISPR-associated Rossman Fold (CARF) domains. Using a comparative genomics approach, and defining a Type III association score accounting for coevolution and specificity of flanking genes, we identified and classified 39 new Type III associated gene families. Most archaeal and bacterial Type III modules were seen to be flanked by several accessory genes, around half of which did not encode CARF domains and remain of unknown function. Northern blotting and interference assays in Synechocystis confirmed that one particular non-CARF accessory protein family was involved in crRNA maturation. Non-CARF accessory genes were generally diverse, encoding nuclease, helicase, protease, ATPase, transporter and transmembrane domains with some encoding no known domains. We infer that additional families of non-CARF accessory proteins remain to be found. The method employed is scalable for potential application to metagenomic data once automated pipelines for annotation of CRISPR-Cas systems have been developed. All accessory genes found in this study are presented online in a readily accessible and searchable format for researchers to audit their model organism of choice: http://accessory.crispr.dk .

  17. Morphology and protein patterns of honey bee drone accessory glands.

    PubMed

    Cruz-Landim, Carminda da; Dallacqua, Rodrigo Pires

    2005-09-30

    We used light and transmission electron microscopy to examine the morphology of the accessory glands of immature and mature adult males of Apis mellifera L. We also made an electrophoretic analysis of the protein content of the mature gland. The glands of the immature male actively secrete a mucous substance that can be seen in the lumen of the gland of the mature male. This secretion stains with mercury bromophenol blue and with periodic acid-Schiff reaction, which stain glyconjugates. The protein content was higher in the lumen secretion than in the gland wall extracts. The electrophoresis patterns of the wall extracts were different from those of the secretion found in the gland lumen.

  18. FK506 binding proteins: cellular regulators of intracellular Ca2+ signalling.

    PubMed

    MacMillan, Debbi

    2013-01-30

    In many cell types the intracellular Ca(2+) store performs a central role in the regulation of the cytosolic Ca(2+) concentration ([Ca(2+)](c)), the elevation of which triggers diverse and fundamental activities from reproduction to apoptosis, as well as being the major trigger for contraction. Two distinct classes of Ca(2+) release channels, which mobilize Ca(2+) from the store, exist; the inositol 1,4,5-trisphosphate (IP(3)) receptor and the ryanodine receptor. Considerable attention has been directed towards the importance of modulatory proteins that interact with these channels including, FK506 binding proteins (FKBPs), FKBP12 and its isoform, FKBP12.6. Although FKBP12 was first identified as the principal intracellular target for the immunosuppressive drugs, FK506 and rapamycin, new insights into the role of FKBPs have since emerged. These regulatory proteins are reportedly important modulators of intracellular Ca(2+) release. FKBPs may regulate ryanodine and IP(3) receptors either directly, by binding to the cytoplasmic aspect of the channel, or indirectly via modulation of two targets, the phosphatase, calcineurin or the kinase, mammalian target of rapamycin (mTOR). Dissociation of FKBP12 or FKBP12.6 from either Ca(2+) release channel may increase, decrease or have no effect on ryanodine receptor- or IP(3) receptor-mediated Ca(2+) release. These important controversies may be attributed to FKBPs' ability to regulate the receptor indirectly via the kinase and phosphatase pathways modulated by the accessory proteins. This brief review discusses the regulation of intracellular ryanodine and IP(3) receptor Ca(2+) release channels by accessory FKBPs, with important implications for the role of FKBPs in the pathophysiology of a number of diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Regucalcin Expression in Bovine Tissues and Its Regulation by Sex Steroid Hormones in Accessory Sex Glands

    PubMed Central

    Starvaggi Cucuzza, Laura; Divari, Sara; Mulasso, Chiara; Biolatti, Bartolomeo; Cannizzo, Francesca T.

    2014-01-01

    Regucalcin (RGN) is a mammalian Ca2+-binding protein that plays an important role in intracellular Ca2+ homeostasis. Recently, RGN has been identified as a target gene for sex steroid hormones in the prostate glands and testis of rats and humans, but no studies have focused on RGN expression in bovine tissues. Thus, in the present study, we examined RGN mRNA and protein expression in the different tissues and organs of veal calves and beef cattle. Moreover, we investigated whether RGN expression is controlled through sex steroid hormones in bovine target tissues, namely the bulbo-urethral and prostate glands and the testis. Sex steroid hormones are still illegally used in bovine husbandry to increase muscle mass. The screening of the regulation and function of anabolic sex steroids via modified gene expression levels in various tissues represents a new approach for the detection of illicit drug treatments. Herein, we used quantitative PCR, western blot and immunohistochemistry analyses to demonstrate RGN mRNA and protein expression in bovine tissues. In addition, estrogen administration down-regulated RGN gene expression in the accessory sex glands of veal calves and beef cattle, while androgen treatment reduced RGN gene expression only in the testis. The confirmation of the regulation of RGN gene expression through sex steroid hormones might facilitate the potential detection of hormone abuse in bovine husbandry. Particularly, the specific response in the testis suggests that this tissue is ideal for the detection of illicit androgen administration in veal calves and beef cattle. PMID:25415588

  20. Multivariate proteomic profiling identifies novel accessory proteins of coated vesicles

    PubMed Central

    Antrobus, Robin; Hirst, Jennifer; Bhumbra, Gary S.; Kozik, Patrycja; Jackson, Lauren P.; Sahlender, Daniela A.

    2012-01-01

    Despite recent advances in mass spectrometry, proteomic characterization of transport vesicles remains challenging. Here, we describe a multivariate proteomics approach to analyzing clathrin-coated vesicles (CCVs) from HeLa cells. siRNA knockdown of coat components and different fractionation protocols were used to obtain modified coated vesicle-enriched fractions, which were compared by stable isotope labeling of amino acids in cell culture (SILAC)-based quantitative mass spectrometry. 10 datasets were combined through principal component analysis into a “profiling” cluster analysis. Overall, 136 CCV-associated proteins were predicted, including 36 new proteins. The method identified >93% of established CCV coat proteins and assigned >91% correctly to intracellular or endocytic CCVs. Furthermore, the profiling analysis extends to less well characterized types of coated vesicles, and we identify and characterize the first AP-4 accessory protein, which we have named tepsin. Finally, our data explain how sequestration of TACC3 in cytosolic clathrin cages causes the severe mitotic defects observed in auxilin-depleted cells. The profiling approach can be adapted to address related cell and systems biological questions. PMID:22472443

  1. Identification and subcellular localization of porcine deltacoronavirus accessory protein NS6

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

    Fang, Puxian; Fang, Liurong; Liu, Xiaorong

    Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Accessory proteins are genus-specific for coronavirus, and two putative accessory proteins, NS6 and NS7, are predicted to be encoded by PDCoV; however, this remains to be confirmed experimentally. Here, we identified the leader-body junction sites of NS6 subgenomic RNA (sgRNA) and found that the actual transcription regulatory sequence (TRS) utilized by NS6 is non-canonical and is located upstream of the predicted TRS. Using the purified NS6 from an Escherichia coli expression system, we obtained two anti-NS6 monoclonal antibodies that could detect the predicted NS6 in cells infected with PDCoV or transfectedmore » with NS6-expressing plasmids. Further studies revealed that NS6 is always localized in the cytoplasm of PDCoV-infected cells, mainly co-localizing with the endoplasmic reticulum (ER) and ER-Golgi intermediate compartments, as well as partially with the Golgi apparatus. Together, our results identify the NS6 sgRNA and demonstrate its expression in PDCoV-infected cells. -- Highlights: •The leader-body fusion site of NS6 sgRNA is identified. •NS6 sgRNA uses a non-canonical transcription regulatory sequence (TRS). •NS6 can be expressed in PDCoV-infected cell. •NS6 predominantly localize to the ER complex and ER-Golgi intermediate compartment.« less

  2. The V-ATPase accessory protein Atp6ap1b mediates dorsal forerunner cell proliferation and left-right asymmetry in zebrafish.

    PubMed

    Gokey, Jason J; Dasgupta, Agnik; Amack, Jeffrey D

    2015-11-01

    Asymmetric fluid flows generated by motile cilia in a transient 'organ of asymmetry' are involved in establishing the left-right (LR) body axis during embryonic development. The vacuolar-type H(+)-ATPase (V-ATPase) proton pump has been identified as an early factor in the LR pathway that functions prior to cilia, but the role(s) for V-ATPase activity are not fully understood. In the zebrafish embryo, the V-ATPase accessory protein Atp6ap1b is maternally supplied and expressed in dorsal forerunner cells (DFCs) that give rise to the ciliated organ of asymmetry called Kupffer's vesicle (KV). V-ATPase accessory proteins modulate V-ATPase activity, but little is known about their functions in development. We investigated Atp6ap1b and V-ATPase in KV development using morpholinos, mutants and pharmacological inhibitors. Depletion of both maternal and zygotic atp6ap1b expression reduced KV organ size, altered cilia length and disrupted LR patterning of the embryo. Defects in other ciliated structures-neuromasts and olfactory placodes-suggested a broad role for Atp6ap1b during development of ciliated organs. V-ATPase inhibitor treatments reduced KV size and identified a window of development in which V-ATPase activity is required for proper LR asymmetry. Interfering with Atp6ap1b or V-ATPase function reduced the rate of DFC proliferation, which resulted in fewer ciliated cells incorporating into the KV organ. Analyses of pH and subcellular V-ATPase localizations suggested Atp6ap1b functions to localize the V-ATPase to the plasma membrane where it regulates proton flux and cytoplasmic pH. These results uncover a new role for the V-ATPase accessory protein Atp6ap1b in early development to maintain the proliferation rate of precursor cells needed to construct a ciliated KV organ capable of generating LR asymmetry. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. The V-ATPase accessory protein Atp6ap1b mediates dorsal forerunner cell proliferation and left-right asymmetry in zebrafish

    PubMed Central

    Gokey, Jason J.; Dasgupta, Agnik; Amack, Jeffrey D.

    2015-01-01

    Asymmetric fluid flows generated by motile cilia in a transient ‘organ of asymmetry’ are involved in establishing the left-right (LR) body axis during embryonic development. The vacuolar-type H+-ATPase (V-ATPase) proton pump has been identified as an early factor in the LR pathway that functions prior to cilia, but the role(s) for V-ATPase activity are not fully understood. In the zebrafish embryo, the V-ATPase accessory protein Atp6ap1b is maternally supplied and expressed in dorsal forerunner cells (DFCs) that give rise to the ciliated organ of asymmetry called Kupffer’s vesicle (KV). V-ATPase accessory proteins modulate V-ATPase activity, but little is known about their functions in development. We investigated Atp6ap1b and V-ATPase in KV development using morpholinos, mutants and pharmacological inhibitors. Depletion of both maternal and zygotic atp6ap1b expression reduced KV organ size, altered cilia length and disrupted LR patterning of the embryo. Defects in other ciliated structures—neuromasts and olfactory placodes—suggested a broad role for Atp6ap1b during development of ciliated organs. V-ATPase inhibitor treatments reduced KV size and identified a window of development in which V-ATPase activity is required for proper LR asymmetry. Interfering with Atp6ap1b or V-ATPase function reduced the rate of DFC proliferation, which resulted in fewer ciliated cells incorporating into the KV organ. Analyses of pH and subcellular V-ATPase localizations suggested Atp6ap1b functions to localize the V-ATPase to the plasma membrane where it regulates proton flux and cytoplasmic pH. These results uncover a new role for the V-ATPase accessory protein Atp6ap1b in early development to maintain the proliferation rate of precursor cells needed to construct a ciliated KV organ capable of generating LR asymmetry. PMID:26254189

  4. Characterisation of different forms of the accessory gp3 canine coronavirus type I protein identified in cats.

    PubMed

    d'Orengiani, Anne-Laure Pham-Hung d'Alexandry; Duarte, Lidia; Pavio, Nicole; Le Poder, Sophie

    2015-04-16

    ORF3 is a supplemental open reading frame coding for an accessory glycoprotein gp3 of unknown function, only present in genotype I canine strain (CCoV-I) and some atypical feline FCoV strains. In these latter hosts, the ORF3 gene systematically displays one or two identical deletions leading to the synthesis of truncated proteins gp3-Δ1 and gp3-Δ2. As deletions in CoV accessory proteins have already been involved in tissue or host switch, studies of these different gp3 proteins were conducted in canine and feline cell. All proteins oligomerise through covalent bonds, are N-glycosylated and are maintained in the ER in non-infected but also in CCoV-II infected cells, without any specific retention signal. However, deletions influence their level of expression. In canine cells, all proteins are expressed with similar level whereas in feline cells, the expression of gp3-Δ1 is higher than the two other forms of gp3. None of the gp3 proteins modulate the viral replication cycle of heterologous genotype II CCoV in canine cell line, leading to the conclusion that the gp3 proteins are probably advantageous only for CCoV-I and atypical FCoV strains. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Up-regulation of Hyperpolarization-activated Cyclic Nucleotide-gated Channel 3 (HCN3) by Specific Interaction with K+ Channel Tetramerization Domain-containing Protein 3 (KCTD3)*

    PubMed Central

    Cao-Ehlker, Xiaochun; Zong, Xiangang; Hammelmann, Verena; Gruner, Christian; Fenske, Stefanie; Michalakis, Stylianos; Wahl-Schott, Christian; Biel, Martin

    2013-01-01

    Most ion channels consist of the principal ion-permeating core subunit(s) and accessory proteins that are assembled with the channel core. The biological functions of the latter proteins are diverse and include the regulation of the biophysical properties of the ion channel, its connection to signaling pathways and the control of its cell surface expression. There is recent evidence that native hyperpolarization-activated cyclic nucleotide-gated channel complexes (HCN1–4) also contain accessory subunits, among which TRIP8b (tetratricopeptide repeat-containing Rab8b-interacting protein) has been most extensively studied. Here, we identify KCTD3, a so far uncharacterized member of the potassium channel tetramerization-domain containing (KCTD) protein family as an HCN3-interacting protein. KCTD3 is widely expressed in brain and some non-neuronal tissues and colocalizes with HCN3 in specific regions of the brain including hypothalamus. Within the HCN channel family, KCTD3 specifically binds to HCN3 and leads to a profound up-regulation of cell surface expression and current density of this channel. HCN3 can also functionally interact with TRIP8b; however, we found no evidence for channel complexes containing both TRIP8b and KCTD3. The C terminus of HCN3 is crucially required for functional interaction with KCTD3. Replacement of the cytosolic C terminus of HCN2 by the corresponding domain of HCN3 renders HCN2 sensitive to regulation by KCTD3. The C-terminal-half of KCTD3 is sufficient for binding to HCN3. However, the complete protein including the N-terminal tetramerization domain is needed for HCN3 current up-regulation. Together, our experiments indicate that KCTD3 is an accessory subunit of native HCN3 complexes. PMID:23382386

  6. Each Monomer of the Dimeric Accessory Protein for Human Mitochondrial DNA Polymerase Has a Distinct Role in Conferring Processivity*

    PubMed Central

    Lee, Young-Sam; Lee, Sujin; Demeler, Borries; Molineux, Ian J.; Johnson, Kenneth A.; Yin, Y. Whitney

    2010-01-01

    The accessory protein polymerase (pol) γB of the human mitochondrial DNA polymerase stimulates the synthetic activity of the catalytic subunit. pol γB functions by both accelerating the polymerization rate and enhancing polymerase-DNA interaction, thereby distinguishing itself from the accessory subunits of other DNA polymerases. The molecular basis for the unique functions of human pol γB lies in its dimeric structure, where the pol γB monomer proximal to pol γA in the holoenzyme strengthens the interaction with DNA, and the distal pol γB monomer accelerates the reaction rate. We further show that human pol γB exhibits a catalytic subunit- and substrate DNA-dependent dimerization. By duplicating the monomeric pol γB of lower eukaryotes, the dimeric mammalian proteins confer additional processivity to the holoenzyme polymerase. PMID:19858216

  7. Isoform-specific functions of Mud/NuMA mediate binucleation of Drosophila male accessory gland cells.

    PubMed

    Taniguchi, Kiichiro; Kokuryo, Akihiko; Imano, Takao; Minami, Ryunosuke; Nakagoshi, Hideki; Adachi-Yamada, Takashi

    2014-12-20

    In standard cell division, the cells undergo karyokinesis and then cytokinesis. Some cells, however, such as cardiomyocytes and hepatocytes, can produce binucleate cells by going through mitosis without cytokinesis. This cytokinesis skipping is thought to be due to the inhibition of cytokinesis machinery such as the central spindle or the contractile ring, but the mechanisms regulating it are unclear. We investigated them by characterizing the binucleation event during development of the Drosophila male accessory gland, in which all cells are binucleate. The accessory gland cells arrested the cell cycle at 50 hours after puparium formation (APF) and in the middle of the pupal stage stopped proliferating for 5 hours. They then restarted the cell cycle and at 55 hours APF entered the M-phase synchronously. At this stage, accessory gland cells binucleated by mitosis without cytokinesis. Binucleating cells displayed the standard karyokinesis progression but also showed unusual features such as a non-round shape, spindle orientation along the apico-basal axis, and poor assembly of the central spindle. Mud, a Drosophila homolog of NuMA, regulated the processes responsible for these three features, the classical isoform Mud(PBD) and the two newly characterized isoforms Mud(L) and Mud(S) regulated them differently: Mud(L) repressed cell rounding, Mud(PBD) and Mud(S) oriented the spindle along the apico-basal axis, and Mud(S) and Mud(L) repressed central spindle assembly. Importantly, overexpression of Mud(S) induced binucleation even in standard proliferating cells such as those in imaginal discs. We characterized the binucleation in the Drosophila male accessory gland and examined mechanisms that regulated unusual morphologies of binucleating cells. We demonstrated that Mud, a microtubule binding protein regulating spindle orientation, was involved in this binucleation. We suggest that atypical functions exerted by three structurally different isoforms of Mud regulate

  8. A multi-scale mathematical modeling framework to investigate anti-viral therapeutic opportunities in targeting HIV-1 accessory proteins

    PubMed Central

    Suryawanshi, Gajendra W.; Hoffmann, Alexander

    2015-01-01

    Human immunodeficiency virus-1 (HIV-1) employs accessory proteins to evade innate immune responses by neutralizing the anti-viral activity of host restriction factors. Apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G, A3G) and bone marrow stromal cell antigen 2 (BST2) are host resistance factors that potentially inhibit HIV-1 infection. BST2 reduces viral production by tethering budding HIV-1 particles to virus producing cells, while A3G inhibits the reverse transcription (RT) process and induces viral genome hypermutation through cytidine deamination, generating fewer replication competent progeny virus. Two HIV-1 proteins counter these cellular restriction factors: Vpu, which reduces surface BST2, and Vif, which degrades cellular A3G. The contest between these host and viral proteins influences whether HIV-1 infection is established and progresses towards AIDS. In this work, we present an age-structured multi-scale viral dynamics model of in vivo HIV-1 infection. We integrated the intracellular dynamics of anti-viral activity of the host factors and their neutralization by HIV-1 accessory proteins into the virus/cell population dynamics model. We calculate the basic reproductive ratio (Ro) as a function of host-viral protein interaction coefficients, and numerically simulated the multi-scale model to understand HIV-1 dynamics following host factor-induced perturbations. We found that reducing the influence of Vpu triggers a drop in Ro, revealing the impact of BST2 on viral infection control. Reducing Vif’s effect reveals the restrictive efficacy of A3G in blocking RT and in inducing lethal hypermutations, however, neither of these factors alone is sufficient to fully restrict HIV-1 infection. Interestingly, our model further predicts that BST2 and A3G function synergistically, and delineates their relative contribution in limiting HIV-1 infection and disease progression. We provide a robust modeling framework for devising novel combination therapies that

  9. Rhabdovirus accessory genes.

    PubMed

    Walker, Peter J; Dietzgen, Ralf G; Joubert, D Albert; Blasdell, Kim R

    2011-12-01

    The Rhabdoviridae is one of the most ecologically diverse families of RNA viruses with members infecting a wide range of organisms including placental mammals, marsupials, birds, reptiles, fish, insects and plants. The availability of complete nucleotide sequences for an increasing number of rhabdoviruses has revealed that their ecological diversity is reflected in the diversity and complexity of their genomes. The five canonical rhabdovirus structural protein genes (N, P, M, G and L) that are shared by all rhabdoviruses are overprinted, overlapped and interspersed with a multitude of novel and diverse accessory genes. Although not essential for replication in cell culture, several of these genes have been shown to have roles associated with pathogenesis and apoptosis in animals, and cell-to-cell movement in plants. Others appear to be secreted or have the characteristics of membrane-anchored glycoproteins or viroporins. However, most encode proteins of unknown function that are unrelated to any other known proteins. Understanding the roles of these accessory genes and the strategies by which rhabdoviruses use them to engage, divert and re-direct cellular processes will not only present opportunities to develop new anti-viral therapies but may also reveal aspects of cellar function that have broader significance in biology, agriculture and medicine. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  10. The Rift Valley fever accessory proteins NSm and P78/NSm-GN are distinct determinants of virus propagation in vertebrate and invertebrate hosts

    PubMed Central

    Kreher, Felix; Tamietti, Carole; Gommet, Céline; Guillemot, Laurent; Ermonval, Myriam; Failloux, Anna-Bella; Panthier, Jean-Jacques; Bouloy, Michèle; Flamand, Marie

    2014-01-01

    Rift Valley fever virus (RVFV) is an enzootic virus circulating in Africa that is transmitted to its vertebrate host by a mosquito vector and causes severe clinical manifestations in humans and ruminants. RVFV has a tripartite genome of negative or ambisense polarity. The M segment contains five in-frame AUG codons that are alternatively used for the synthesis of two major structural glycoproteins, GN and GC, and at least two accessory proteins, NSm, a 14-kDa cytosolic protein, and P78/NSm-GN, a 78-kDa glycoprotein. To determine the relative contribution of P78 and NSm to RVFV infectivity, AUG codons were knocked out to generate mutant viruses expressing various sets of the M-encoded proteins. We found that, in the absence of the second AUG codon used to express NSm, a 13-kDa protein corresponding to an N-terminally truncated form of NSm, named NSm′, was synthesized from AUG 3. None of the individual accessory proteins had any significant impact on RVFV virulence in mice. However, a mutant virus lacking both NSm and NSm′ was strongly attenuated in mice and grew to reduced titers in murine macrophages, a major target cell type of RVFV. In contrast, P78 was not associated with reduced viral virulence in mice, yet it appeared as a major determinant of virus dissemination in mosquitoes. This study demonstrates how related accessory proteins differentially contribute to RVFV propagation in mammalian and arthropod hosts. PMID:26038497

  11. Multiple functional roles of the accessory I-domain of bacteriophage P22 coat protein revealed by NMR structure and cryoEM modeling

    PubMed Central

    Rizzo, Alessandro A.; Suhanovsky, Margaret M.; Baker, Matthew L.; Fraser, LaTasha C.R.; Jones, Lisa M.; Rempel, Don L.; Gross, Michael L.; Chiu, Wah; Alexandrescu, Andrei T.; Teschke, Carolyn M.

    2014-01-01

    SUMMARY Some capsid proteins built on the ubiquitous HK97-fold have accessory domains that impart specific functions. Bacteriophage P22 coat protein has a unique inserted I-domain. Two prior I-domain models from sub-nanometer cryoEM reconstructions differed substantially. Therefore, the NMR structure of the I-domain was determined, which also was used to improve cryoEM models of coat protein. The I-domain has an anti-parallel 6-stranded β-barrel fold, previously not observed in HK97-fold accessory domains. The D-loop, which is dynamic both in the isolated I-domain and intact monomeric coat protein, forms stabilizing salt bridges between adjacent capsomers in procapsids. A newly described S-loop is important for capsid size determination, likely through intra-subunit interactions. Ten of eighteen coat protein temperature-sensitive-folding substitutions are in the I-domain, indicating its importance in folding and stability. Several are found on a positively charged face of the β-barrel that anchors the I-domain to a negatively charged surface of the coat protein HK97-core. PMID:24836025

  12. Multiple functional roles of the accessory I-domain of bacteriophage P22 coat protein revealed by NMR structure and CryoEM modeling.

    PubMed

    Rizzo, Alessandro A; Suhanovsky, Margaret M; Baker, Matthew L; Fraser, LaTasha C R; Jones, Lisa M; Rempel, Don L; Gross, Michael L; Chiu, Wah; Alexandrescu, Andrei T; Teschke, Carolyn M

    2014-06-10

    Some capsid proteins built on the ubiquitous HK97-fold have accessory domains imparting specific functions. Bacteriophage P22 coat protein has a unique insertion domain (I-domain). Two prior I-domain models from subnanometer cryoelectron microscopy (cryoEM) reconstructions differed substantially. Therefore, the I-domain's nuclear magnetic resonance structure was determined and also used to improve cryoEM models of coat protein. The I-domain has an antiparallel six-stranded β-barrel fold, not previously observed in HK97-fold accessory domains. The D-loop, which is dynamic in the isolated I-domain and intact monomeric coat protein, forms stabilizing salt bridges between adjacent capsomers in procapsids. The S-loop is important for capsid size determination, likely through intrasubunit interactions. Ten of 18 coat protein temperature-sensitive-folding substitutions are in the I-domain, indicating its importance in folding and stability. Several are found on a positively charged face of the β-barrel that anchors the I-domain to a negatively charged surface of the coat protein HK97-core. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Cas13d Is a Compact RNA-Targeting Type VI CRISPR Effector Positively Modulated by a WYL-Domain-Containing Accessory Protein.

    PubMed

    Yan, Winston X; Chong, Shaorong; Zhang, Huaibin; Makarova, Kira S; Koonin, Eugene V; Cheng, David R; Scott, David A

    2018-04-19

    Bacterial class 2 CRISPR-Cas systems utilize a single RNA-guided protein effector to mitigate viral infection. We aggregated genomic data from multiple sources and constructed an expanded database of predicted class 2 CRISPR-Cas systems. A search for novel RNA-targeting systems identified subtype VI-D, encoding dual HEPN domain-containing Cas13d effectors and putative WYL-domain-containing accessory proteins (WYL1 and WYL-b1 through WYL-b5). The median size of Cas13d proteins is 190 to 300 aa smaller than that of Cas13a-Cas13c. Despite their small size, Cas13d orthologs from Eubacterium siraeum (Es) and Ruminococcus sp. (Rsp) are active in both CRISPR RNA processing and targeting, as well as collateral RNA cleavage, with no target-flanking sequence requirements. The RspWYL1 protein stimulates RNA cleavage by both EsCas13d and RspCas13d, demonstrating a common regulatory mechanism for divergent Cas13d orthologs. The small size, minimal targeting constraints, and modular regulation of Cas13d effectors further expands the CRISPR toolkit for RNA manipulation and detection. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. VPAC receptors: structure, molecular pharmacology and interaction with accessory proteins.

    PubMed

    Couvineau, Alain; Laburthe, Marc

    2012-05-01

    The vasoactive intestinal peptide (VIP) is a neuropeptide with wide distribution in both central and peripheral nervous systems, where it plays important regulatory role in many physiological processes. VIP displays a large biological functions including regulation of exocrine secretions, hormone release, fetal development, immune responses, etc. VIP appears to exert beneficial effect in neuro-degenerative and inflammatory diseases. The mechanism of action of VIP implicates two subtypes of receptors (VPAC1 and VPAC2), which are members of class B receptors belonging to the super-family of GPCR. This article reviews the current knowledge regarding the structure and molecular pharmacology of VPAC receptors. The structure-function relationship of VPAC1 receptor has been extensively studied, allowing to understand the molecular basis for receptor affinity, specificity, desensitization and coupling to adenylyl cyclase. Those studies have clearly demonstrated the crucial role of the N-terminal ectodomain (N-ted) of VPAC1 receptor in VIP recognition. By using different approaches including directed mutagenesis, photoaffinity labelling, NMR, molecular modelling and molecular dynamic simulation, it has been shown that the VIP molecule interacts with the N-ted of VPAC1 receptor, which is itself structured as a 'Sushi' domain. VPAC1 receptor also interacts with a few accessory proteins that play a role in cell signalling of receptors. Recent advances in the structural characterization of VPAC receptor and more generally of class B GPCRs will lead to the design of new molecules, which could have considerable interest for the treatment of inflammatory and neuro-degenerative diseases. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  15. Interleukin (IL)-1 in rat parturition: IL-1 receptors 1 and 2 and accessory proteins abundance in pregnant rat uterus at term - regulation by progesterone.

    PubMed

    Ishiguro, Tomohito; Takeda, Jun; Fang, Xin; Bronson, Heather; Olson, David M

    2016-07-01

    The role of interleukin-1 (IL-1), a pro-inflammatory cytokine, in parturition is typically noted by changes in its concentrations. Studying the expression of its receptor family, IL-1 receptor (IL-1R) 1, IL-1R2, IL-1R accessory protein (IL-1RAcP), and its predominantly brain isoform, IL-1RAcPb, during late gestation in the uterus in the Long-Evans rat is another. We assessed changes in their mRNA and protein relative abundance in the uterus and compared IL-1RAcP and IL-1RAcPb mRNA abundance in uterus, cervix, ovaries, placenta, and whole blood of Long-Evans rats during late gestation or in RU486 and progesterone-treated dams using quantitative real-time PCR and western immunoblotting. IL-1R1, IL-1RAcP, and IL-1RAcPb mRNA abundance significantly increased in the uterus at delivery whereas IL-1R2 mRNA abundance significantly decreased. IL-1R1 protein increased at term and IL-1R2 protein decreased at term compared to nonpregnant uteri. IL1-RAcPb mRNA abundance was less than IL-1RAcP, but in the lower uterine segment it was the highest of all tissues examined. RU486 stimulated preterm delivery and an increase in IL-1R1 mRNA abundance whereas progesterone administration extended pregnancy and suppressed the increase in IL-1R1. These data suggest that changes in uterine sensitivity to IL-1 occur during late gestation and suggest another level of regulation for the control of delivery. The roles for IL-1RAcP and IL-1RAcPb need to be determined, but may relate to different intracellular signaling pathways. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  16. Association of estradiol on expression of melanocortin receptors and their accessory proteins in the liver of chicken (Gallus gallus).

    PubMed

    Ren, Junxiao; Li, Yanmin; Xu, Naiyi; Li, Hong; Li, Cuicui; Han, Ruili; Wang, Yanbin; Li, Zhuanjian; Kang, Xiangtao; Liu, Xiaojun; Tian, Yadong

    2017-01-01

    The melanocortin receptor accessory proteins (MRAP and MRAP2) are small single-pass transmembrane proteins that regulate the biological functions of the melanocortin receptor (MCR) family. MCRs comprise five receptors (MC1R-MC5R) with diverse physiological roles in mammals. Five MCR members and two MRAPs were also predicted in the chicken (Gallus gallus) genome. However, little is known about their expression, regulation and biological functions. In this study, we cloned the MRAP and MRAP2 genes. Sequencing analysis revealed that the functional domains of MRAP and MRAP2 were conserved among species, suggesting that the physiological roles of chicken MRAP and MRAP2 could be similar to their mammalian counterparts. Tissue expression analysis demonstrated that MRAP was expressed in the adrenal gland, liver, spleen, glandular stomach and lungs, while MRAP2 is predominantly expressed in the adrenal gland. All five MCRs were present in the adrenal gland, but showed different expression patterns in other tissues. The MC5R was the only MCR member that was expressed in the chicken liver. The expression levels of MRAP in chicken liver were significantly increased at sexual maturity stage, and were significantly up-regulated (P<0.05) when chickens and chicken primary hepatocytes were treated with 17β-estradiol in vivo and in vitro, respectively; however, expression levels of PPARγ were down-regulated, and no effect on MC5R was observed. Our results suggested that estrogen could stimulate the expression of MRAP in the liver of chicken through inhibiting the expression of transcription regulation factor PPARγ, and MRAP might play its biological role in a different way rather than forming an MRAP/MC2R complex in chicken liver during the egg-laying period. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Potential role of Arabidopsis PHP as an accessory subunit of the PAF1 transcriptional cofactor.

    PubMed

    Park, Sunchung; Ek-Ramos, Maria Julissa; Oh, Sookyung; van Nocker, Steven

    2011-08-01

    Paf1C is a transcriptional cofactor that has been implicated in various transcription-associated mechanisms spanning initiation, elongation and RNA processing, and is important for multiple aspects of development in Arabidopsis. Our recent studies suggest Arabidopsis Paf1C is crucial for proper regulation of genes within H3K27me3-enriched chromatin, and that a protein named PHP may act as an accessory subunit of Paf1C that promotes this function.

  18. Iron oxide nanoparticles modulate heat shock proteins and organ specific markers expression in mice male accessory organs

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

    Sundarraj, Kiruthika; Raghunath, Azhwar; Panneerse

    With increased industrial utilization of iron oxide nanoparticles (Fe{sub 2}O{sub 3}-NPs), concerns on adverse reproductive health effects following exposure have been immensely raised. In the present study, the effects of Fe{sub 2}O{sub 3}-NPs exposure in the seminal vesicle and prostate gland were studied in mice. Mice were exposed to two different doses (25 and 50 mg/kg) of Fe{sub 2}O{sub 3}-NPs along with the control and analyzed the expressions of heat shock proteins (HSP60, HSP70 and HSP90) and organ specific markers (Caltrin, PSP94, and SSLP1). Fe{sub 2}O{sub 3}-NPs decreased food consumption, water intake, and organo-somatic index in mice with elevated ironmore » levels in serum, urine, fecal matter, seminal vesicle and prostate gland. FTIR spectra revealed alterations in the functional groups of biomolecules on Fe{sub 2}O{sub 3}-NPs treatment. These changes are accompanied by increased lactate dehydrogenase levels with decreased total protein and fructose levels. The investigation of oxidative stress biomarkers demonstrated a significant increase in reactive oxygen species, nitric oxide, lipid peroxidation, protein carbonyl content and glutathione peroxidase with a concomitant decrement in the glutathione and ascorbic acid in the male accessory organs which confirmed the induction of oxidative stress. An increase in NADPH-oxidase-4 with a decrease in glutathione-S-transferase was observed in the seminal vesicle and prostate gland of the treated groups. An alteration in HSP60, HSP70, HSP90, Caltrin, PSP94, and SSLP1 expression was also observed. Moreover, accumulation of Fe{sub 2}O{sub 3}-NPs brought pathological changes in the seminal vesicle and prostate gland of treated mice. These findings provide evidence that Fe{sub 2}O{sub 3}-NPs could be an environmental risk factor for reproductive disease. - Highlights: • Fe{sub 2}O{sub 3}-NPs caused adverse effects on the seminal vesicle and prostate gland of mice • Heat shock proteins (Hsp60, 70 and 90

  19. Estrogen receptor accessory proteins augment receptor-DNA interaction and DNA bending.

    PubMed

    Landel, C C; Potthoff, S J; Nardulli, A M; Kushner, P J; Greene, G L

    1997-01-01

    Increasing evidence suggests that accessory proteins play an important role in the ability of the estrogen receptor (ER) and other nuclear hormone receptors to modulate transcription when bound to cis-acting hormone response elements in target genes. We have previously shown that four proteins, hsp70, protein disulfide isomerase (PDI) and two unknown proteins (p48 and p45), copurify with ER that has been isolated by site-specific DNA chromatography (BERE) and influence the interaction of ER with DNA in vitro. To better define the nature of these effects, we used filter binding and electrophoretic mobility shift assays to study the ability of these proteins to alter the kinetics of ER-DNA interaction and to influence the ability of ER to bend DNA when bound to an estrogen response element (ERE). The results of both assays indicate that ERE-purified ER, with its four associated proteins (hsp70, PDI, p48, p45), has a greater ability to bind to the vitellogenin A2 ERE than ER purified by estradiol-Sepharose chromatography in the absence (ESeph) or presence (EATP) of ATP, in which p48, p45 (ESeph) and hsp70 (EATP) are removed. Surprisingly, the rates of association and dissociation of ER and ERE were essentially the same for all three mixtures, suggesting that one or more ER-associated proteins, especially p45 and p48, may be required for ER to attain maximum DNA binding activity. In addition, circular permutation and phasing analyses demonstrated that the same ER-associated proteins produced higher order ER-DNA complexes that significantly increased the magnitude of DNA distortion, but did not alter the direction of the ER-induced bend of ERE-containing DNA fragments, which was toward the major groove of the DNA helix. These results suggest that p45 and/or p48 and possibly hsp70, play an important role both in the specific DNA binding and bending activities of ER and thus contribute to the overall stimulation of transcription in target genes that contain cis

  20. Transcription Factors Encoded on Core and Accessory Chromosomes of Fusarium oxysporum Induce Expression of Effector Genes

    PubMed Central

    van der Does, H. Charlotte; Schmidt, Sarah M.; Langereis, Léon; Hughes, Timothy R.

    2016-01-01

    Proteins secreted by pathogens during host colonization largely determine the outcome of pathogen-host interactions and are commonly called ‘effectors’. In fungal plant pathogens, coordinated transcriptional up-regulation of effector genes is a key feature of pathogenesis and effectors are often encoded in genomic regions with distinct repeat content, histone code and rate of evolution. In the tomato pathogen Fusarium oxysporum f. sp. lycopersici (Fol), effector genes reside on one of four accessory chromosomes, known as the ‘pathogenicity’ chromosome, which can be exchanged between strains through horizontal transfer. The three other accessory chromosomes in the Fol reference strain may also be important for virulence towards tomato. Expression of effector genes in Fol is highly up-regulated upon infection and requires Sge1, a transcription factor encoded on the core genome. Interestingly, the pathogenicity chromosome itself contains 13 predicted transcription factor genes and for all except one, there is a homolog on the core genome. We determined DNA binding specificity for nine transcription factors using oligonucleotide arrays. The binding sites for homologous transcription factors were highly similar, suggesting that extensive neofunctionalization of DNA binding specificity has not occurred. Several DNA binding sites are enriched on accessory chromosomes, and expression of FTF1, its core homolog FTF2 and SGE1 from a constitutive promoter can induce expression of effector genes. The DNA binding sites of only these three transcription factors are enriched among genes up-regulated during infection. We further show that Ftf1, Ftf2 and Sge1 can activate transcription from their binding sites in yeast. RNAseq analysis revealed that in strains with constitutive expression of FTF1, FTF2 or SGE1, expression of a similar set of plant-responsive genes on the pathogenicity chromosome is induced, including most effector genes. We conclude that the Fol

  1. An Accessory Protein Required for Anchoring and Assembly of Amyloid Fibers in B. subtilis Biofilms

    PubMed Central

    Romero, Diego; Vlamakis, Hera; Losick, Richard; Kolter, Roberto

    2011-01-01

    Cells within Bacillus subtilis biofilms are held in place by an extracellular matrix that contains cell-anchored amyloid fibers, composed of the amyloidogenic protein TasA. As biofilms age they disassemble because the cells release the amyloid fibers. This release appears to be the consequence of incorporation of D-tyrosine, D-leucine, D-tryptophan and D-methionine into the cell wall. Here, we characterize the in vivo roles of an accessory protein TapA (TasA anchoring/assembly protein; previously YqxM) that serves both to anchor the fibers to the cell wall and to assemble TasA into fibers. TapA is found in discrete foci in the cell envelope and these foci disappear when cells are treated with a mixture of D-amino acids. Purified cell wall sacculi retain a functional form of this anchoring protein such that purified fibers can be anchored to the sacculi in vitro. In addition, we show that TapA is essential for the proper assembly of the fibers. Its absence results in a dramatic reduction in TasA levels and what little TasA is left produces only thin fibers that are not anchored to the cell. PMID:21477127

  2. The Laser Accessory Market

    NASA Astrophysics Data System (ADS)

    Desai, Ashvin

    1988-09-01

    Wandering through the exhibit hall yesterday, I noticed that if you look at the laser companies and if you look at the accessory companies, there are pretty much the same number of accessory booths as well as the laser companies. There was one difference. Laser company booths are all sexy looking, very flashy, big booths. Whereas if you look at the accessories booths, they were small, not so prominent.

  3. 14 CFR 23.1163 - Powerplant accessories.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... section, be sealed to prevent contamination of the engine oil system and the accessory system. (b... engine is hazardous when malfunctioning occurs, a means to prevent rotation without interfering with the... Controls and Accessories § 23.1163 Powerplant accessories. (a) Each engine mounted accessory must— (1) Be...

  4. 14 CFR 23.1163 - Powerplant accessories.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... section, be sealed to prevent contamination of the engine oil system and the accessory system. (b... engine is hazardous when malfunctioning occurs, a means to prevent rotation without interfering with the... Controls and Accessories § 23.1163 Powerplant accessories. (a) Each engine mounted accessory must— (1) Be...

  5. 14 CFR 23.1163 - Powerplant accessories.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... section, be sealed to prevent contamination of the engine oil system and the accessory system. (b... engine is hazardous when malfunctioning occurs, a means to prevent rotation without interfering with the... Controls and Accessories § 23.1163 Powerplant accessories. (a) Each engine mounted accessory must— (1) Be...

  6. 14 CFR 23.1163 - Powerplant accessories.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... section, be sealed to prevent contamination of the engine oil system and the accessory system. (b... engine is hazardous when malfunctioning occurs, a means to prevent rotation without interfering with the... Controls and Accessories § 23.1163 Powerplant accessories. (a) Each engine mounted accessory must— (1) Be...

  7. Kicking against the PRCs – A Domesticated Transposase Antagonises Silencing Mediated by Polycomb Group Proteins and Is an Accessory Component of Polycomb Repressive Complex 2

    PubMed Central

    Perera, Pumi; Mora-García, Santiago; de Leau, Erica; Thornton, Harry; de Alves, Flavia Lima; Rapsilber, Juri; Yang, Suxin; James, Geo Velikkakam; Schneeberger, Korbinian; Finnegan, E. Jean; Turck, Franziska; Goodrich, Justin

    2015-01-01

    The Polycomb group (PcG) and trithorax group (trxG) genes play crucial roles in development by regulating expression of homeotic and other genes controlling cell fate. Both groups catalyse modifications of chromatin, particularly histone methylation, leading to epigenetic changes that affect gene activity. The trxG antagonizes the function of PcG genes by activating PcG target genes, and consequently trxG mutants suppress PcG mutant phenotypes. We previously identified the ANTAGONIST OF LIKE HETEROCHROMATIN PROTEIN1 (ALP1) gene as a genetic suppressor of mutants in the Arabidopsis PcG gene LIKE HETEROCHROMATIN PROTEIN1 (LHP1). Here, we show that ALP1 interacts genetically with several other PcG and trxG components and that it antagonizes PcG silencing. Transcriptional profiling reveals that when PcG activity is compromised numerous target genes are hyper-activated in seedlings and that in most cases this requires ALP1. Furthermore, when PcG activity is present ALP1 is needed for full activation of several floral homeotic genes that are repressed by the PcG. Strikingly, ALP1 does not encode a known chromatin protein but rather a protein related to PIF/Harbinger class transposases. Phylogenetic analysis indicates that ALP1 is broadly conserved in land plants and likely lost transposase activity and acquired a novel function during angiosperm evolution. Consistent with this, immunoprecipitation and mass spectrometry (IP-MS) show that ALP1 associates, in vivo, with core components of POLYCOMB REPRESSIVE COMPLEX 2 (PRC2), a widely conserved PcG protein complex which functions as a H3K27me3 histone methyltransferase. Furthermore, in reciprocal pulldowns using the histone methyltransferase CURLY LEAF (CLF), we identify not only ALP1 and the core PRC2 components but also plant-specific accessory components including EMBRYONIC FLOWER 1 (EMF1), a transcriptional repressor previously associated with PRC1-like complexes. Taken together our data suggest that ALP1 inhibits Pc

  8. Protein Interactions and Localization of the Escherichia coli Accessory Protein HypA during Nickel Insertion to [NiFe] Hydrogenase*

    PubMed Central

    Chan Chung, Kim C.; Zamble, Deborah B.

    2011-01-01

    Nickel delivery during maturation of Escherichia coli [NiFe] hydrogenase 3 includes the accessory proteins HypA, HypB, and SlyD. Although the isolated proteins have been characterized, little is known about how they interact with each other and the hydrogenase 3 large subunit, HycE. In this study the complexes of HypA and HycE were investigated after modification with the Strep-tag II. Multiprotein complexes containing HypA, HypB, SlyD, and HycE were observed, consistent with the assembly of a single nickel insertion cluster. An interaction between HypA and HycE did not require the other nickel insertion proteins, but HypB was not found with the large subunit in the absence of HypA. The HypA-HycE complex was not detected in the absence of the HypC or HypD proteins, involved in the preceding iron insertion step, and this interaction is enhanced by nickel brought into the cell by the NikABCDE membrane transporter. Furthermore, without the hydrogenase 1, 2, and 3 large subunits, complexes between HypA, HypB, and SlyD were observed. These results support the hypothesis that HypA acts as a scaffold for assembly of the nickel insertion proteins with the hydrogenase precursor protein after delivery of the iron center. At different stages of the hydrogenase maturation process, HypA was observed at or near the cell membrane by using fluorescence confocal microscopy, as was HycE, suggesting membrane localization of the nickel insertion event. PMID:22016389

  9. An accessory protein required for anchoring and assembly of amyloid fibres in B. subtilis biofilms.

    PubMed

    Romero, Diego; Vlamakis, Hera; Losick, Richard; Kolter, Roberto

    2011-06-01

    Cells within Bacillus subtilis biofilms are held in place by an extracellular matrix that contains cell-anchored amyloid fibres, composed of the amyloidogenic protein TasA. As biofilms age they disassemble because the cells release the amyloid fibres. This release appears to be the consequence of incorporation of D-tyrosine, D-leucine, D-tryptophan and D-methionine into the cell wall. Here, we characterize the in vivo roles of an accessory protein TapA (TasA anchoring/assembly protein; previously YqxM) that serves both to anchor the fibres to the cell wall and to assemble TasA into fibres. TapA is found in discrete foci in the cell envelope and these foci disappear when cells are treated with a mixture of D-amino acids. Purified cell wall sacculi retain a functional form of this anchoring protein such that purified fibres can be anchored to the sacculi in vitro. In addition, we show that TapA is essential for the proper assembly of the fibres. Its absence results in a dramatic reduction in TasA levels and what little TasA is left produces only thin fibres that are not anchored to the cell. © 2011 Blackwell Publishing Ltd.

  10. MRAP2 regulates ghrelin receptor signaling and hunger sensing.

    PubMed

    Srisai, Dollada; Yin, Terry C; Lee, Abigail A; Rouault, Alix A J; Pearson, Nicole A; Grobe, Justin L; Sebag, Julien A

    2017-09-28

    Ghrelin is the only known circulating orexigenic hormone. It is primarily secreted by the stomach and acts at its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), in the hypothalamus to signal hunger and promote food intake. The melanocortin receptor accessory protein 2 (MRAP2) was previously shown to regulate energy homeostasis through the modulation of the activity of the melanocortin-4 receptor and prokineticin receptors. In this study we identify MRAP2 as a partner of ghrelin-GHSR1a signaling. We show that MRAP2 interacts with GHSR1a and potentiates ghrelin-stimulated signaling both in vitro and in vivo. We demonstrate that in the absence of MRAP2, fasting fails to activate agouti-related protein neurons. In addition, we show that the orexigenic effect of ghrelin is lost in mice lacking MRAP2. Our results suggest that MRAP2 is an important modulator of the energy homeostasis machinery that operates through the regulation of multiple GPCRs throughout the hypothalamus.Melanocortin receptor accessory protein 2 (MRAP2) is an adaptor protein that contributes to melanocortin-4 receptor and prokineticin receptor 1 signalling. Here the authors show that MRAP2 also regulates ghrelin receptor signalling in the hypothalamus and starvation sensing in mice.

  11. Adrenocorticotropic Hormone (ACTH) Responses Require Actions of the Melanocortin-2 Receptor Accessory Protein on the Extracellular Surface of the Plasma Membrane.

    PubMed

    Malik, Sundeep; Dolan, Terrance M; Maben, Zachary J; Hinkle, Patricia M

    2015-11-13

    The melanocortin-2 (MC2) receptor is a G protein-coupled receptor that mediates responses to ACTH. The MC2 receptor acts in concert with the MC2 receptor accessory protein (MRAP) that is absolutely required for ACTH binding and signaling. MRAP has a single transmembrane domain and forms a highly unusual antiparallel homodimer that is stably associated with MC2 receptors at the plasma membrane. Despite the physiological importance of the interaction between the MC2 receptor and MRAP, there is little understanding of how the accessory protein works. The dual topology of MRAP has made it impossible to determine whether highly conserved and necessary regions of MRAP are required on the intracellular or extracellular face of the plasma membrane. The strategy used here was to fix the orientation of two antiparallel MRAP molecules and then introduce inactivating mutations on one side of the membrane or the other. This was achieved by engineering proteins containing tandem copies of MRAP fused to the amino terminus of the MC2 receptor. The data firmly establish that only the extracellular amino terminus (Nout) copy of MRAP, oriented with critical segments on the extracellular side of the membrane, is essential. The transmembrane domain of MRAP is also required in only the Nout orientation. Finally, activity of MRAP-MRAP-MC2-receptor fusion proteins with inactivating mutations in either MRAP or the receptor was rescued by co-expression of free wild-type MRAP or free wild-type receptor. These results show that the basic MRAP-MRAP-receptor signaling unit forms higher order complexes and that these multimers signal. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Staphylococcus aureus regulates the expression and production of the staphylococcal superantigen-like secreted proteins in a Rot-dependent manner.

    PubMed

    Benson, Meredith A; Lilo, Sarit; Wasserman, Gregory A; Thoendel, Matthew; Smith, Amanda; Horswill, Alexander R; Fraser, John; Novick, Richard P; Shopsin, Bo; Torres, Victor J

    2011-08-01

    Staphylococcus aureus overproduces a subset of immunomodulatory proteins known as the staphylococcal superantigen-like proteins (Ssls) under conditions of pore-mediated membrane stress. In this study we demonstrate that overproduction of Ssls during membrane stress is due to the impaired activation of the two-component module of the quorum-sensing accessory gene regulator (Agr) system. Agr-dependent repression of ssl expression is indirect and mediated by the transcription factor repressor of toxins (Rot). Surprisingly, we observed that Rot directly interacts with and activates the ssl promoters. The role of Agr and Rot as regulators of ssl expression was observed across several clinically relevant strains, suggesting that overproduction of immunomodulatory proteins benefits agr-defective strains. In support of this notion, we demonstrate that Ssls contribute to the residual virulence of S. aureus lacking agr in a murine model of systemic infection. Altogether, these results suggest that S. aureus compensates for the inactivation of Agr by producing immunomodulatory exoproteins that could protect the bacterium from host-mediated clearance. © 2011 Blackwell Publishing Ltd.

  13. 14 CFR 25.1163 - Powerplant accessories.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... the engine oil system and the accessory system. (b) Electrical equipment subject to arcing or sparking... to prevent rotation without interfering with the continued operation of the engine. [Doc. No. 5066... Powerplant accessories. (a) Each engine mounted accessory must— (1) Be approved for mounting on the engine...

  14. 14 CFR 25.1163 - Powerplant accessories.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... the engine oil system and the accessory system. (b) Electrical equipment subject to arcing or sparking... to prevent rotation without interfering with the continued operation of the engine. [Doc. No. 5066... Powerplant accessories. (a) Each engine mounted accessory must— (1) Be approved for mounting on the engine...

  15. 14 CFR 25.1163 - Powerplant accessories.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... the engine oil system and the accessory system. (b) Electrical equipment subject to arcing or sparking... to prevent rotation without interfering with the continued operation of the engine. [Doc. No. 5066... Powerplant accessories. (a) Each engine mounted accessory must— (1) Be approved for mounting on the engine...

  16. 14 CFR 25.1163 - Powerplant accessories.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... the engine oil system and the accessory system. (b) Electrical equipment subject to arcing or sparking... to prevent rotation without interfering with the continued operation of the engine. [Doc. No. 5066... Powerplant accessories. (a) Each engine mounted accessory must— (1) Be approved for mounting on the engine...

  17. Synthesis, depletion and cell-type expression of a protein from the male accessory glands of the dengue vector mosquito Aedes aegypti

    PubMed Central

    Alfonso-Parra, Catalina; Avila, Frank W.; Deewatthanawong, Prasit; Sirot, Laura K.; Wolfner, Mariana F.; Harrington, Laura C.

    2014-01-01

    Aedes aegypti males transfer sperm and seminal fluid proteins (Sfps), primarily produced by male accessory glands (AGs), to females during mating. When collectively injected or transplanted into females, AG tissues and/or seminal fluid homogenates have profound effects on Aedes female physiology and behavior. To identify targets and design new strategies for vector control, it is important to understand the biology of the AGs. Thus, we examined characteristics of AG secretion and development in Ae. aegypti, using the AG-specific seminal fluid protein, AAEL010824, as a marker. We showed that AAEL010824 is first detectable by 12h post-eclosion, and increases in amount over the first 3 days of adult life. We then showed that the amount of AAEL0010824 in the AG decreases after mating, with each successive mating depleting it further; by 5 successive matings with no time for recovery, its levels are very low. AAEL010824 levels in a depleted male are replenished by 48hr post-mating. In addition to examining the level of AAEL010824 protein, we also characterized the expression of its gene. We did this by making a transgenic mosquito line that carries an Enhanced Green Fluorescence Protein (EGFP) fused to the AAEL0010824 promoter that we defined here. We showed that AAEL010824 is expressed in the anterior cells of the accessory glands, and that its RNA levels also respond to mating. In addition to further characterizing AAEL010824 expression, our results with the EGFP fusion provide a promoter for driving AG expression. By providing this information on the biology of an important male reproductive tissue and the production of one of its seminal proteins, our results lay the foundation for future work aimed at identifying novel targets for mosquito population control. PMID:25107876

  18. Accessory genes confer a high replication rate to virulent feline immunodeficiency virus.

    PubMed

    Troyer, Ryan M; Thompson, Jesse; Elder, John H; VandeWoude, Sue

    2013-07-01

    Feline immunodeficiency virus (FIV) is a lentivirus that causes AIDS in domestic cats, similar to human immunodeficiency virus (HIV)/AIDS in humans. The FIV accessory protein Vif abrogates the inhibition of infection by cat APOBEC3 restriction factors. FIV also encodes a multifunctional OrfA accessory protein that has characteristics similar to HIV Tat, Vpu, Vpr, and Nef. To examine the role of vif and orfA accessory genes in FIV replication and pathogenicity, we generated chimeras between two FIV molecular clones with divergent disease potentials: a highly pathogenic isolate that replicates rapidly in vitro and is associated with significant immunopathology in vivo, FIV-C36 (referred to here as high-virulence FIV [HV-FIV]), and a less-pathogenic strain, FIV-PPR (referred to here as low-virulence FIV [LV-FIV]). Using PCR-driven overlap extension, we produced viruses in which vif, orfA, or both genes from virulent HV-FIV replaced equivalent genes in LV-FIV. The generation of these chimeras is more straightforward in FIV than in primate lentiviruses, since FIV accessory gene open reading frames have very little overlap with other genes. All three chimeric viruses exhibited increased replication kinetics in vitro compared to the replication kinetics of LV-FIV. Chimeras containing HV-Vif or Vif/OrfA had replication rates equivalent to those of the virulent HV-FIV parental virus. Furthermore, small interfering RNA knockdown of feline APOBEC3 genes resulted in equalization of replication rates between LV-FIV and LV-FIV encoding HV-FIV Vif. These findings demonstrate that Vif-APOBEC interactions play a key role in controlling the replication and pathogenicity of this immunodeficiency-inducing virus in its native host species and that accessory genes act as mediators of lentiviral strain-specific virulence.

  19. 21 CFR 878.4960 - Operating tables and accessories and operating chairs and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Operating tables and accessories and operating chairs and accessories. 878.4960 Section 878.4960 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical...

  20. 21 CFR 878.4960 - Operating tables and accessories and operating chairs and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Operating tables and accessories and operating chairs and accessories. 878.4960 Section 878.4960 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical...

  1. 21 CFR 878.4960 - Operating tables and accessories and operating chairs and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Operating tables and accessories and operating chairs and accessories. 878.4960 Section 878.4960 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical...

  2. 21 CFR 878.4960 - Operating tables and accessories and operating chairs and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Operating tables and accessories and operating chairs and accessories. 878.4960 Section 878.4960 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical...

  3. 21 CFR 878.4960 - Operating tables and accessories and operating chairs and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Operating tables and accessories and operating chairs and accessories. 878.4960 Section 878.4960 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical...

  4. MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis

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

    Menachery, Vineet D.; Mitchell, Hugh D.; Cockrell, Adam S.

    ABSTRACT While dispensable for viral replication, coronavirus (CoV) accessory open reading frame (ORF) proteins often play critical roles during infection and pathogenesis. Utilizing a previously generated mutant, we demonstrate that the absence of all four Middle East respiratory syndrome CoV (MERS-CoV) accessory ORFs (deletion of ORF3, -4a, -4b, and -5 [dORF3-5]) has major implications for viral replication and pathogenesis. Importantly, attenuation of the dORF3-5 mutant is primarily driven by dysregulated host responses, including disrupted cell processes, augmented interferon (IFN) pathway activation, and robust inflammation.In vitroreplication attenuation also extends toin vivomodels, allowing use of dORF3-5 as a live attenuated vaccine platform.more » Finally, examination of ORF5 implicates a partial role in modulation of NF-κB-mediated inflammation. Together, the results demonstrate the importance of MERS-CoV accessory ORFs for pathogenesis and highlight them as potential targets for surveillance and therapeutic treatments moving forward. IMPORTANCEThe initial emergence and periodic outbreaks of MERS-CoV highlight a continuing threat posed by zoonotic pathogens to global public health. In these studies, mutant virus generation demonstrates the necessity of accessory ORFs in regard to MERS-CoV infection and pathogenesis. With this in mind, accessory ORF functions can be targeted for both therapeutic and vaccine treatments in response to MERS-CoV and related group 2C coronaviruses. In addition, disruption of accessory ORFs in parallel may offer a rapid response platform to attenuation of future emergent strains based on both SARS- and MERS-CoV accessory ORF mutants.« less

  5. 14 CFR 29.1163 - Powerplant accessories.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Powerplant accessories. (a) Each engine mounted accessory must— (1) Be approved for mounting on the engine involved; (2) Use the provisions on the engine for mounting; and (3) Be sealed in such a way as to prevent contamination of the engine oil system and the accessory system. (b) Electrical equipment subject to arcing or...

  6. 14 CFR 29.1163 - Powerplant accessories.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Powerplant accessories. (a) Each engine mounted accessory must— (1) Be approved for mounting on the engine involved; (2) Use the provisions on the engine for mounting; and (3) Be sealed in such a way as to prevent contamination of the engine oil system and the accessory system. (b) Electrical equipment subject to arcing or...

  7. 14 CFR 29.1163 - Powerplant accessories.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Powerplant accessories. (a) Each engine mounted accessory must— (1) Be approved for mounting on the engine involved; (2) Use the provisions on the engine for mounting; and (3) Be sealed in such a way as to prevent contamination of the engine oil system and the accessory system. (b) Electrical equipment subject to arcing or...

  8. 14 CFR 29.1163 - Powerplant accessories.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Powerplant accessories. (a) Each engine mounted accessory must— (1) Be approved for mounting on the engine involved; (2) Use the provisions on the engine for mounting; and (3) Be sealed in such a way as to prevent contamination of the engine oil system and the accessory system. (b) Electrical equipment subject to arcing or...

  9. Molecular landscape of the interaction between the urease accessory proteins UreE and UreG.

    PubMed

    Merloni, Anna; Dobrovolska, Olena; Zambelli, Barbara; Agostini, Federico; Bazzani, Micaela; Musiani, Francesco; Ciurli, Stefano

    2014-09-01

    Urease, the most efficient enzyme so far discovered, depends on the presence of nickel ions in the catalytic site for its activity. The transformation of inactive apo-urease into active holo-urease requires the insertion of two Ni(II) ions in the substrate binding site, a process that involves the interaction of four accessory proteins named UreD, UreF, UreG and UreE. This study, carried out using calorimetric and NMR-based structural analysis, is focused on the interaction between UreE and UreG from Sporosarcina pasteurii, a highly ureolytic bacterium. Isothermal calorimetric protein-protein titrations revealed the occurrence of a binding event between SpUreE and SpUreG, entailing two independent steps with positive cooperativity (Kd1=42±9μM; Kd2=1.7±0.3μM). This was interpreted as indicating the formation of the (UreE)2(UreG)2 hetero-oligomer upon binding of two UreG monomers onto the pre-formed UreE dimer. The molecular details of this interaction were elucidated using high-resolution NMR spectroscopy. The occurrence of SpUreE chemical shift perturbations upon addition of SpUreG was investigated and analyzed to establish the protein-protein interaction site. The latter appears to involve the Ni(II) binding site as well as mobile portions on the C-terminal and the N-terminal domains. Docking calculations based on the information obtained from NMR provided a structural basis for the protein-protein contact site. The high sequence and structural similarity within these protein classes suggests a generality of the interaction mode among homologous proteins. The implications of these results on the molecular details of the urease activation process are considered and analyzed. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Identification of a basic protein of Mr 75,000 as an accessory desmosomal plaque protein in stratified and complex epithelia.

    PubMed

    Kapprell, H P; Owaribe, K; Franke, W W

    1988-05-01

    Desmosomes are intercellular adhering junctions characterized by a special structure and certain obligatory constituent proteins such as the cytoplasmic protein, desmoglein. Desmosomal fractions from bovine muzzle epidermis contain, in addition, a major polypeptide of Mr approximately 75,000 ("band 6 protein") which differs from all other desmosomal proteins so far identified by its positive charge (isoelectric at pH approximately 8.5 in the denatured state) and its avidity to bind certain type I cytokeratins under stringent conditions. We purified this protein from bovine muzzle epidermis and raised antibodies to it. Using affinity-purified antibodies, we identified a protein of identical SDS-PAGE mobility and isoelectric pH in all epithelia of higher complexity, including representatives of stratified, complex (pseudostratified) and transitional epithelia as well as benign and malignant human tumors derived from such epithelia. Immunolocalization studies revealed the location of this protein along cell boundaries in stratified and complex epithelia, often resolved into punctate arrays. In some epithelia it seemed to be restricted to certain cell types and layers; in rat cornea, for example, it was only detected in upper strata. Electron microscopic immunolocalization showed that this protein is a component of the desmosomal plaque. However, it was not found in the desmosomes of all simple epithelia examined, in the tumors and cultured cells derived thereof, in myocardiac and Purkinje fiber cells, in arachnoideal cells and meningiomas, and in dendritic reticulum cells of lymphoid tissue, i.e., all cells containing typical desmosomes. The protein was also absent in all nondesmosomal adhering junctions. From these results we conclude that this basic protein is not an obligatory desmosomal plaque constituent but an accessory component specific to the desmosomes of certain kinds of epithelial cells with stratified tissue architecture. This suggests that the Mr 75

  11. Drosophila Fatty Acid Transport Protein Regulates Rhodopsin-1 Metabolism and Is Required for Photoreceptor Neuron Survival

    PubMed Central

    Dourlen, Pierre; Bertin, Benjamin; Chatelain, Gilles; Robin, Marion; Napoletano, Francesco; Roux, Michel J.; Mollereau, Bertrand

    2012-01-01

    Tight regulation of the visual response is essential for photoreceptor function and survival. Visual response dysregulation often leads to photoreceptor cell degeneration, but the causes of such cell death are not well understood. In this study, we investigated a fatty acid transport protein (fatp) null mutation that caused adult-onset and progressive photoreceptor cell death. Consistent with fatp having a role in the retina, we showed that fatp is expressed in adult photoreceptors and accessory cells and that its re-expression in photoreceptors rescued photoreceptor viability in fatp mutants. The visual response in young fatp-mutant flies was abnormal with elevated electroretinogram amplitudes associated with high levels of Rhodopsin-1 (Rh1). Reducing Rh1 levels in rh1 mutants or depriving flies of vitamin A rescued photoreceptor cell death in fatp mutant flies. Our results indicate that fatp promotes photoreceptor survival by regulating Rh1 abundance. PMID:22844251

  12. Possible role of the Nipah virus V protein in the regulation of the interferon beta induction by interacting with UBX domain-containing protein1.

    PubMed

    Uchida, Shotaro; Horie, Ryo; Sato, Hiroki; Kai, Chieko; Yoneda, Misako

    2018-05-16

    Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes lethal encephalitis in humans. We previously reported that the V protein, one of the three accessory proteins encoded by the P gene, is one of the key determinants of the pathogenesis of NiV in a hamster infection model. Satterfield B.A. et al. have also revealed that V protein is required for the pathogenicity of henipavirus in a ferret infection model. However, the complete functions of NiV V have not been clarified. In this study, we identified UBX domain-containing protein 1 (UBXN1), a negative regulator of RIG-I-like receptor signaling, as a host protein that interacts with NiV V. NiV V interacted with the UBX domain of UBXN1 via its proximal zinc-finger motif in the C-terminal domain. NiV V increased the level of UBXN1 protein by suppressing its proteolysis. Furthermore, NiV V suppressed RIG-I and MDA5-dependent interferon signaling by stabilizing UBXN1 and increasing the interaction between MAVS and UBXN1 in addition to directly interrupting the activation of MDA5. Our results suggest a novel molecular mechanism by which the induction of interferon is potentially suppressed by NiV V protein via UBXN1.

  13. Tissue specificity of the hormonal response in sex accessory tissues is associated with nuclear matrix protein patterns.

    PubMed

    Getzenberg, R H; Coffey, D S

    1990-09-01

    The DNA of interphase nuclei have very specific three-dimensional organizations that are different in different cell types, and it is possible that this varying DNA organization is responsible for the tissue specificity of gene expression. The nuclear matrix organizes the three-dimensional structure of the DNA and is believed to be involved in the control of gene expression. This study compares the nuclear structural proteins between two sex accessory tissues in the same animal responding to the same androgen stimulation by the differential expression of major tissue-specific secretory proteins. We demonstrate here that the nuclear matrix is tissue specific in the rat ventral prostate and seminal vesicle, and undergoes characteristic alterations in its protein composition upon androgen withdrawal. Three types of nuclear matrix proteins were observed: 1) nuclear matrix proteins that are different and tissue specific in the rat ventral prostate and seminal vesicle, 2) a set of nuclear matrix proteins that either appear or disappear upon androgen withdrawal, and 3) a set of proteins that are common to both the ventral prostate and seminal vesicle and do not change with the hormonal state of the animal. Since the nuclear matrix is known to bind androgen receptors in a tissue- and steroid-specific manner, we propose that the tissue specificity of the nuclear matrix arranges the DNA in a unique conformation, which may be involved in the specific interaction of transcription factors with DNA sequences, resulting in tissue-specific patterns of secretory protein expression.

  14. Accessory Muscles of the Extremities.

    PubMed

    Vanhoenacker, Filip M; Desimpel, Julie; Mespreuve, Marc; Tagliafico, Alberto

    2018-07-01

    Accessory muscles and variations are not uncommon at the upper and lower extremity. They are often overlooked because they are asymptomatic and present as incidental findings on imaging. However, they may present as a soft tissue swelling, thereby mimicking soft tissue tumors. Other symptoms are attributed to impingement on neurovascular structures and to exercise-related pain. Thorough knowledge of the anatomy, systematic imaging analysis, and the awareness of it are the clues to correct identification. On ultrasound, accessory muscles have a similar echotexture as other muscles, whereas the signal intensity on magnetic resonance imaging (MRI) is similar to muscle. Because of the intrinsic contrast with the adjacent intermuscular fat, accessory muscles are best depicted on MRI without fat suppression. This article provides a short overview of the anatomy of most prevalent accessory muscles of the upper and lower limb and its potential pathogenic nature. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. 21 CFR 878.4350 - Cryosurgical unit and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and accessories. (a) Identification—(1) Cryosurgical unit with a liquid nitrogen cooled cryoprobe and accessories. A cryosurgical unit with a liquid nitrogen cooled cryoprobe and accessories is a device intended...

  16. MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis

    PubMed Central

    Menachery, Vineet D.; Mitchell, Hugh D.; Cockrell, Adam S.; Gralinski, Lisa E.; Yount, Boyd L.; Graham, Rachel L.; McAnarney, Eileen T.; Douglas, Madeline G.; Scobey, Trevor; Beall, Anne; Dinnon, Kenneth; Kocher, Jacob F.; Hale, Andrew E.; Stratton, Kelly G.; Waters, Katrina M.

    2017-01-01

    ABSTRACT While dispensable for viral replication, coronavirus (CoV) accessory open reading frame (ORF) proteins often play critical roles during infection and pathogenesis. Utilizing a previously generated mutant, we demonstrate that the absence of all four Middle East respiratory syndrome CoV (MERS-CoV) accessory ORFs (deletion of ORF3, -4a, -4b, and -5 [dORF3-5]) has major implications for viral replication and pathogenesis. Importantly, attenuation of the dORF3-5 mutant is primarily driven by dysregulated host responses, including disrupted cell processes, augmented interferon (IFN) pathway activation, and robust inflammation. In vitro replication attenuation also extends to in vivo models, allowing use of dORF3-5 as a live attenuated vaccine platform. Finally, examination of ORF5 implicates a partial role in modulation of NF-κB-mediated inflammation. Together, the results demonstrate the importance of MERS-CoV accessory ORFs for pathogenesis and highlight them as potential targets for surveillance and therapeutic treatments moving forward. PMID:28830941

  17. 21 CFR 878.4950 - Manual operating table and accessories and manual operating chair and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Manual operating table and accessories and manual operating chair and accessories. 878.4950 Section 878.4950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES...

  18. 21 CFR 878.4950 - Manual operating table and accessories and manual operating chair and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Manual operating table and accessories and manual operating chair and accessories. 878.4950 Section 878.4950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES...

  19. 21 CFR 878.4950 - Manual operating table and accessories and manual operating chair and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Manual operating table and accessories and manual operating chair and accessories. 878.4950 Section 878.4950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES...

  20. 21 CFR 878.4950 - Manual operating table and accessories and manual operating chair and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Manual operating table and accessories and manual operating chair and accessories. 878.4950 Section 878.4950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES...

  1. 21 CFR 878.4950 - Manual operating table and accessories and manual operating chair and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Manual operating table and accessories and manual operating chair and accessories. 878.4950 Section 878.4950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES...

  2. 14 CFR 25.1163 - Powerplant accessories.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Powerplant accessories. (a) Each engine mounted accessory must— (1) Be approved for mounting on the engine involved; (2) Use the provisions on the engine for mounting; and (3) Be sealed to prevent contamination of...

  3. Structure of UreG/UreF/UreH Complex Reveals How Urease Accessory Proteins Facilitate Maturation of Helicobacter pylori Urease

    PubMed Central

    Fong, Yu Hang; Wong, Ho Chun; Yuen, Man Hon; Lau, Pak Ho; Chen, Yu Wai; Wong, Kam-Bo

    2013-01-01

    Urease is a metalloenzyme essential for the survival of Helicobacter pylori in acidic gastric environment. Maturation of urease involves carbamylation of Lys219 and insertion of two nickel ions at its active site. This process requires GTP hydrolysis and the formation of a preactivation complex consisting of apo-urease and urease accessory proteins UreF, UreH, and UreG. UreF and UreH form a complex to recruit UreG, which is a SIMIBI class GTPase, to the preactivation complex. We report here the crystal structure of the UreG/UreF/UreH complex, which illustrates how UreF and UreH facilitate dimerization of UreG, and assembles its metal binding site by juxtaposing two invariant Cys66-Pro67-His68 metal binding motif at the interface to form the (UreG/UreF/UreH)2 complex. Interaction studies revealed that addition of nickel and GTP to the UreG/UreF/UreH complex releases a UreG dimer that binds a nickel ion at the dimeric interface. Substitution of Cys66 and His68 with alanine abolishes the formation of the nickel-charged UreG dimer. This nickel-charged UreG dimer can activate urease in vitro in the presence of the UreF/UreH complex. Static light scattering and atomic absorption spectroscopy measurements demonstrated that the nickel-charged UreG dimer, upon GTP hydrolysis, reverts to its monomeric form and releases nickel to urease. Based on our results, we propose a mechanism on how urease accessory proteins facilitate maturation of urease. PMID:24115911

  4. 14 CFR 29.1163 - Powerplant accessories.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Powerplant accessories. (a) Each engine mounted accessory must— (1) Be approved for mounting on the engine involved; (2) Use the provisions on the engine for mounting; and (3) Be sealed in such a way as to prevent...

  5. 14 CFR 27.1163 - Powerplant accessories.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Powerplant accessories. (a) Each engine-mounted accessory must— (1) Be approved for mounting on the engine involved; (2) Use the provisions on the engine for mounting; and (3) Be sealed in such a way as to prevent...

  6. IL-10 down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells through decreased antigen uptake via the mannose receptor and lowered surface expression of accessory molecules.

    PubMed

    Knolle, P A; Uhrig, A; Hegenbarth, S; Löser, E; Schmitt, E; Gerken, G; Lohse, A W

    1998-12-01

    Our study demonstrates that antigen-presenting liver sinusoidal endothelial cells (LSEC) induce production of interferon-gamma (IFN-gamma) from cloned Th1 CD4+ T cells. We show that LSEC used the mannose receptor for antigen uptake, which further strengthened the role of LSEC as antigen-presenting cell (APC) population in the liver. The ability of LSEC to activate cloned CD4+ T cells antigen-specifically was down-regulated by exogenous prostaglandin E2 (PGE2) and by IL-10. We identify two separate mechanisms by which IL-10 down-regulated T cell activation through LSEC. IL-10 decreased the constitutive surface expression of MHC class II as well as of the accessory molecules CD80 and CD86 on LSEC. Furthermore, IL-10 diminished mannose receptor activity in LSEC. Decreased antigen uptake via the mannose receptor and decreased expression of accessory molecules may explain the down-regulation of T cell activation through IL-10. Importantly, the expression of low numbers of antigen on MHC II in the absence of accessory signals on LSEC may lead to induction of anergy in T cells. Because PGE2 and IL-10 are released from LSEC or Kupffer cells (KC) in response to those concentrations of endotoxin found physiologically in portal venous blood, it is possible that the continuous presence of these mediators and their negative effect on the local APC may explain the inability of the liver to induce T cell activation and to clear chronic infections. Our results support the notion that antigen presentation by LSEC in the hepatic microenvironment contributes to the observed inability to mount an effective cell-mediated immune response in the liver.

  7. 21 CFR 884.6120 - Assisted reproduction accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... II (special controls) (design specifications, labeling requirements, and clinical testing). ... Assisted reproduction accessories. (a) Identification. Assisted reproduction accessories are a group of...

  8. 21 CFR 884.6120 - Assisted reproduction accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... II (special controls) (design specifications, labeling requirements, and clinical testing). ... Assisted reproduction accessories. (a) Identification. Assisted reproduction accessories are a group of...

  9. 21 CFR 884.6120 - Assisted reproduction accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... II (special controls) (design specifications, labeling requirements, and clinical testing). ... Assisted reproduction accessories. (a) Identification. Assisted reproduction accessories are a group of...

  10. 21 CFR 872.3980 - Endosseous dental implant accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Endosseous dental implant accessories. 872.3980... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3980 Endosseous dental implant accessories. (a) Identification. Endosseous dental implant accessories are manually powered devices intended...

  11. 21 CFR 872.3980 - Endosseous dental implant accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Endosseous dental implant accessories. 872.3980... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3980 Endosseous dental implant accessories. (a) Identification. Endosseous dental implant accessories are manually powered devices intended...

  12. 21 CFR 872.3980 - Endosseous dental implant accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Endosseous dental implant accessories. 872.3980... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3980 Endosseous dental implant accessories. (a) Identification. Endosseous dental implant accessories are manually powered devices intended...

  13. 21 CFR 872.3980 - Endosseous dental implant accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endosseous dental implant accessories. 872.3980... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3980 Endosseous dental implant accessories. (a) Identification. Endosseous dental implant accessories are manually powered devices intended...

  14. 21 CFR 872.3980 - Endosseous dental implant accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Endosseous dental implant accessories. 872.3980... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3980 Endosseous dental implant accessories. (a) Identification. Endosseous dental implant accessories are manually powered devices intended...

  15. Differential reinforcement of enzymatic hydrolysis by adding chemicals and accessory proteins to high solid loading substrates with different pretreatments.

    PubMed

    Du, Jian; Song, Wenxia; Zhang, Xiu; Zhao, Jian; Liu, Guodong; Qu, Yinbo

    2018-04-23

    High dosage of enzyme is required to achieve effective lignocellulose hydrolysis, especially at high-solid loadings, which is a significant barrier to large-scale bioconversion of lignocellulose. Here, we screened four chemical additives and three accessory proteins for their effects on the enzymatic hydrolysis of various lignocellulosic materials. The effects were found to be highly dependent on the composition and solid loadings of substrates. For xylan-extracted lignin-rich corncob residue, the enhancing effect of PEG 6000 was most pronounced and negligibly affected by solid content, which reduced more than half of enzyme demand at 20% dry matter (DM). Lytic polysaccharide monooxygenase enhanced the hydrolysis of ammonium sulfite wheat straw pulp, and its addition reduced about half of protein demand at the solid loading of 20% DM. Supplementation of the additives in the hydrolysis of pure cellulose and complex lignocellulosic materials revealed that their effects are tightly linked to pretreatment strategies.

  16. 21 CFR 876.5250 - Urine collector and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Urine collector and accessories. 876.5250 Section... (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5250 Urine collector and accessories. (a) Identification. A urine collector and accessories is a device intended to collect...

  17. 21 CFR 876.5250 - Urine collector and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Urine collector and accessories. 876.5250 Section... (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5250 Urine collector and accessories. (a) Identification. A urine collector and accessories is a device intended to collect...

  18. 21 CFR 876.5250 - Urine collector and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Urine collector and accessories. 876.5250 Section... (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5250 Urine collector and accessories. (a) Identification. A urine collector and accessories is a device intended to collect...

  19. 21 CFR 876.5250 - Urine collector and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Urine collector and accessories. 876.5250 Section... (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5250 Urine collector and accessories. (a) Identification. A urine collector and accessories is a device intended to collect...

  20. 21 CFR 876.5250 - Urine collector and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Urine collector and accessories. 876.5250 Section... (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5250 Urine collector and accessories. (a) Identification. A urine collector and accessories is a device intended to collect...

  1. 21 CFR 868.5860 - Pressure tubing and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pressure tubing and accessories. 868.5860 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5860 Pressure tubing and accessories. (a) Identification. Pressure tubing and accessories are flexible or rigid devices intended to...

  2. Endocytosis of the seven-transmembrane RGS1 protein activates G-protein-coupled signalling in Arabidopsis.

    PubMed

    Urano, Daisuke; Phan, Nguyen; Jones, Janice C; Yang, Jing; Huang, Jirong; Grigston, Jeffrey; Taylor, J Philip; Jones, Alan M

    2012-10-01

    Signal transduction typically begins by ligand-dependent activation of a concomitant partner that is otherwise in its resting state. However, in cases where signal activation is constitutive by default, the mechanism of regulation is unknown. The Arabidopsis thaliana heterotrimeric Gα protein self-activates without accessory proteins, and is kept in its resting state by the negative regulator, AtRGS1 (regulator of G-protein signalling 1), which is the prototype of a seven-transmembrane receptor fused with an RGS domain. Endocytosis of AtRGS1 by ligand-dependent endocytosis physically uncouples the GTPase-accelerating activity of AtRGS1 from the Gα protein, permitting sustained activation. Phosphorylation of AtRGS1 by AtWNK8 kinase causes AtRGS1 endocytosis, required for both G-protein-mediated sugar signalling and cell proliferation. In animals, receptor endocytosis results in signal desensitization, whereas in plants, endocytosis results in signal activation. These findings reveal how different organisms rearrange a regulatory system to result in opposite outcomes using similar phosphorylation-dependent endocytosis mechanisms.

  3. Three Accessories for a Rotating Platform.

    ERIC Educational Resources Information Center

    Riley, James A.; Fryer, Oscar G.

    1980-01-01

    Describes three accessories developed to be used in conjunction with the rotating platform or turntable. Three demonstrations using these accessories are included. These demonstrations are: (a) conservation of angular momentum; (b) gravity-defying goblets; and (c) direct measurement of centripetal force. (HM)

  4. 14 CFR 25.1192 - Engine accessory section diaphragm.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Engine accessory section diaphragm. 25.1192....1192 Engine accessory section diaphragm. For reciprocating engines, the engine power section and all portions of the exhaust system must be isolated from the engine accessory compartment by a diaphragm that...

  5. 14 CFR 25.1192 - Engine accessory section diaphragm.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Engine accessory section diaphragm. 25.1192....1192 Engine accessory section diaphragm. For reciprocating engines, the engine power section and all portions of the exhaust system must be isolated from the engine accessory compartment by a diaphragm that...

  6. 14 CFR 25.1192 - Engine accessory section diaphragm.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Engine accessory section diaphragm. 25.1192....1192 Engine accessory section diaphragm. For reciprocating engines, the engine power section and all portions of the exhaust system must be isolated from the engine accessory compartment by a diaphragm that...

  7. 21 CFR 872.4200 - Dental handpiece and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Dental handpiece and accessories. 872.4200 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4200 Dental handpiece and accessories. (a) Identification. A dental handpiece and accessories is an AC-powered, water-powered, air-powered, or belt-driven...

  8. 21 CFR 872.4200 - Dental handpiece and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Dental handpiece and accessories. 872.4200 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4200 Dental handpiece and accessories. (a) Identification. A dental handpiece and accessories is an AC-powered, water-powered, air-powered, or belt-driven...

  9. 21 CFR 872.4200 - Dental handpiece and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Dental handpiece and accessories. 872.4200 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4200 Dental handpiece and accessories. (a) Identification. A dental handpiece and accessories is an AC-powered, water-powered, air-powered, or belt-driven...

  10. 21 CFR 872.4200 - Dental handpiece and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Dental handpiece and accessories. 872.4200 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4200 Dental handpiece and accessories. (a) Identification. A dental handpiece and accessories is an AC-powered, water-powered, air-powered, or belt-driven...

  11. 21 CFR 872.4200 - Dental handpiece and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Dental handpiece and accessories. 872.4200 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4200 Dental handpiece and accessories. (a) Identification. A dental handpiece and accessories is an AC-powered, water-powered, air-powered, or belt-driven...

  12. 21 CFR 876.5900 - Ostomy pouch and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ostomy pouch and accessories. 876.5900 Section 876...) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5900 Ostomy pouch and accessories. (a) Identification. An ostomy pouch and accessories is a device that consists of a bag that is...

  13. 21 CFR 872.6250 - Dental chair and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Dental chair and accessories. 872.6250 Section 872...) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6250 Dental chair and accessories. (a) Identification. A dental chair and accessories is a device, usually AC-powered, in which a patient sits. The...

  14. 21 CFR 872.6250 - Dental chair and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Dental chair and accessories. 872.6250 Section 872...) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6250 Dental chair and accessories. (a) Identification. A dental chair and accessories is a device, usually AC-powered, in which a patient sits. The...

  15. 21 CFR 872.6250 - Dental chair and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Dental chair and accessories. 872.6250 Section 872...) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6250 Dental chair and accessories. (a) Identification. A dental chair and accessories is a device, usually AC-powered, in which a patient sits. The...

  16. 21 CFR 872.6250 - Dental chair and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Dental chair and accessories. 872.6250 Section 872...) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6250 Dental chair and accessories. (a) Identification. A dental chair and accessories is a device, usually AC-powered, in which a patient sits. The...

  17. 21 CFR 872.6250 - Dental chair and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Dental chair and accessories. 872.6250 Section 872...) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6250 Dental chair and accessories. (a) Identification. A dental chair and accessories is a device, usually AC-powered, in which a patient sits. The...

  18. Accessories make the outfit: Accessory Chromosomes and other dispensable DNA regions in plant-pathogenic Fungi.

    PubMed

    Bertazzoni, Stefania; Williams, Angela; Jones, Darcy A B; Syme, Robert A; Tan, Kar-Chun; Hane, James Kyawzwar

    2018-04-17

    Fungal pathogen genomes can often be divided into core and accessory regions. Accessory regions may be comprised of either accessory regions (ARs) within core chromosomes (CCs), or wholly-dispensable (accessory) chromosomes (ACs). Fungal ACs and ARs typically accumulate mutations and structural rearrangements more rapidly over time than CCs, and many harbour genes relevant to host-pathogen interactions. These regions are of particular interest in plant pathology and include host-specific virulence factors and secondary metabolite synthesis gene clusters. This review outlines known ACs and ARs in fungal genomes, methods used for their detection, their common properties that differentiate them from the core genome, and what is currently known of their various roles in pathogenicity. Reports on the evolutionary processes generating and shaping AC/AR compartments are discussed, including repeat induced point mutation (RIP) and breakage-fusion-bridge (BFB) cycles. Previously ACs have been studied extensively within key genera including Fusarium, Zymoseptoria and Alternaria, but are growing in their frequency of observation and perceived importance across a wider range of fungal species. Recent advances in sequencing technologies permit affordable genome assembly and re-sequencing of populations that will facilitate further discovery and routine screening of ACs.

  19. Male accessory gland proteins induce female monogamy in anopheline mosquitoes.

    PubMed

    Shutt, B; Stables, L; Aboagye-Antwi, F; Moran, J; Tripet, F

    2010-03-01

    The role of male accessory gland (MAG) secretions in inducing refractoriness to further mating in mosquitoes (Diptera: Culicidae) was established in the late 1960s. In a set of simple experiments, MAG extract was injected intra-thoraxically into the hemocoel of virgin Aedes aegypti (L.), Culex pipiens pipiens (L.) and Anopheles quadrimaculatus Say females. This subsequently caused most females to remain unmated when exposed to males. For anophelines these findings were later challenged by a study involving intra-abdominal injections of MAG extracts into Anopheles gambiae Giles s.l. and Anopheles albimanus Wiedmann females, which failed to induce refractoriness to further mating. These findings led to controversy about the respective role of sperm and accessory gland peptides in inducing female monogamy in Anopheles and are at odds with our current understanding of the mating process in Drosophila spp. (Diptera: Drosophillidae) and other dipterans. Here we confirm the function of MAG secretions in anophelines experimentally by showing that intra-thoracic injections in Anopheles stephensi Liston and in the M and S molecular forms of An. gambiae s.s. result in the expected female monogamy. Cross-injections of MAG extracts between the M and S molecular forms of An. gambiae, two cryptic taxa within An. gambiae s.s. which are thought to be undergoing incipient speciation, also elicited effective refractoriness, suggesting that the two sub-taxa have not diverged with regard to sex peptides responsible for female monogamy. Importantly, this also suggests that the rare cases of re-mating following cross-mating observed in this species may not be a form of reproductive barrier between molecular forms.

  20. 21 CFR 890.5925 - Traction accessory.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Traction accessory. 890.5925 Section 890.5925 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5925 Traction accessory. (a...

  1. 21 CFR 890.5925 - Traction accessory.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Traction accessory. 890.5925 Section 890.5925 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5925 Traction accessory. (a...

  2. 21 CFR 890.5925 - Traction accessory.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Traction accessory. 890.5925 Section 890.5925 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5925 Traction accessory. (a...

  3. 21 CFR 890.5925 - Traction accessory.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Traction accessory. 890.5925 Section 890.5925 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5925 Traction accessory. (a...

  4. 21 CFR 890.5925 - Traction accessory.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Traction accessory. 890.5925 Section 890.5925 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5925 Traction accessory. (a...

  5. 47 CFR 15.27 - Special accessories.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... information required by this section may be included in the manual in that alternative form, provided the user..., shall ensure that these special accessories are provided with the equipment. The instruction manual for... responsibility of the user to use the needed special accessories supplied with the equipment. In cases where the...

  6. Future Development of Endoscopic Accessories for Endoscopic Submucosal Dissection

    PubMed Central

    Jang, Jae-Young

    2017-01-01

    Endoscopic submucosal dissection (ESD) has recently been accepted as a standard treatment for patients with early gastric cancer (EGC), without lymph node metastases. Given the rise in the number of ESDs being performed, new endoscopic accessories are being developed and existing accessories modified to facilitate the execution of ESD and reduce complication rates. This paper examines the history underlying the development of these new endoscopic accessories and indicates future directions for the development of these accessories. PMID:28609819

  7. HIV-1 Nef binds with human GCC185 protein and regulates mannose 6 phosphate receptor recycling

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

    Kumar, Manjeet; Kaur, Supinder; Nazir, Aamir

    HIV-1 Nef modulates cellular function that enhances viral replication in vivo which culminate into AIDS pathogenesis. With no enzymatic activity, Nef regulates cellular function through host protein interaction. Interestingly, trans-cellular introduction of recombinant Nef protein in Caenorhabditis elegans results in AIDS like pathogenesis which might share common pathophysiology because the gene sequence of C. elegans and humans share considerable homology. Therefore employing C. elegans based initial screen complemented with sequence based homology search we identified GCC185 as novel host protein interacting with HIV-1 Nef. The detailed molecular characterization revealed N-terminal EEEE{sub 65} acidic domain of Nef as key region for interaction. GCC185 ismore » a tethering protein that binds with Rab9 transport vesicles. Our results show that Nef-GCC185 interaction disrupts Rab9 interaction resulting in delocalization of CI-MPR (cation independent Mannose 6 phosphate receptor) resulting in elevated secretion of hexosaminidase. In agreement with this, our studies identified novel host GCC185 protein that interacts with Nef EEEE65 acidic domain interfering GCC185-Rab9 vesicle membrane fusion responsible for retrograde vesicular transport of CI-MPR from late endosomes to TGN. In light of existing report suggesting critical role of Nef-GCC185 interaction reveals valuable mechanistic insights affecting specific protein transport pathway in docking of late endosome derived Rab9 bearing transport vesicle at TGN elucidating role of Nef during viral pathogenesis. -- Highlights: •Nef, an accessory protein of HIV-1 interacts with host factor and culminates into AIDS pathogenesis. •Using Caenorhabditis elegans based screen system, novel Nef interacting cellular protein GCC185 was identified. •Molecular characterization of Nef and human protein GCC185 revealed Nef EEEE{sub 65} key region interacted with full length GCC185. •Nef impeded the GCC185-Rab 9

  8. 21 CFR 876.1500 - Endoscope and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... within this generic type of device include cleaning accessories for endoscopes, photographic accessories for endoscopes, nonpowered anoscopes, binolcular attachments for endoscopes, pocket battery boxes... endoscope, smoke removal tube, rechargeable battery box, pocket battery box, bite block for endoscope, and...

  9. 21 CFR 876.1500 - Endoscope and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... within this generic type of device include cleaning accessories for endoscopes, photographic accessories for endoscopes, nonpowered anoscopes, binolcular attachments for endoscopes, pocket battery boxes... endoscope, smoke removal tube, rechargeable battery box, pocket battery box, bite block for endoscope, and...

  10. 21 CFR 876.1500 - Endoscope and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... within this generic type of device include cleaning accessories for endoscopes, photographic accessories for endoscopes, nonpowered anoscopes, binolcular attachments for endoscopes, pocket battery boxes... endoscope, smoke removal tube, rechargeable battery box, pocket battery box, bite block for endoscope, and...

  11. 21 CFR 876.1500 - Endoscope and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... within this generic type of device include cleaning accessories for endoscopes, photographic accessories for endoscopes, nonpowered anoscopes, binolcular attachments for endoscopes, pocket battery boxes... endoscope, smoke removal tube, rechargeable battery box, pocket battery box, bite block for endoscope, and...

  12. 21 CFR 876.1500 - Endoscope and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... within this generic type of device include cleaning accessories for endoscopes, photographic accessories for endoscopes, nonpowered anoscopes, binolcular attachments for endoscopes, pocket battery boxes... endoscope, smoke removal tube, rechargeable battery box, pocket battery box, bite block for endoscope, and...

  13. 21 CFR 872.4920 - Dental electrosurgical unit and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Dental electrosurgical unit and accessories. 872... SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4920 Dental electrosurgical unit and accessories. (a) Identification. A dental electrosurgical unit and accessories is an AC-powered...

  14. 21 CFR 872.4920 - Dental electrosurgical unit and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Dental electrosurgical unit and accessories. 872... SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4920 Dental electrosurgical unit and accessories. (a) Identification. A dental electrosurgical unit and accessories is an AC-powered...

  15. 21 CFR 872.4920 - Dental electrosurgical unit and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Dental electrosurgical unit and accessories. 872... SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4920 Dental electrosurgical unit and accessories. (a) Identification. A dental electrosurgical unit and accessories is an AC-powered...

  16. 21 CFR 872.4920 - Dental electrosurgical unit and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Dental electrosurgical unit and accessories. 872... SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4920 Dental electrosurgical unit and accessories. (a) Identification. A dental electrosurgical unit and accessories is an AC-powered...

  17. 21 CFR 872.4920 - Dental electrosurgical unit and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Dental electrosurgical unit and accessories. 872... SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4920 Dental electrosurgical unit and accessories. (a) Identification. A dental electrosurgical unit and accessories is an AC-powered...

  18. 21 CFR 872.4120 - Bone cutting instrument and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Bone cutting instrument and accessories. 872.4120... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4120 Bone cutting instrument and accessories. (a) Identification. A bone cutting instrument and accessories is a metal device intended for use...

  19. 21 CFR 872.4120 - Bone cutting instrument and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Bone cutting instrument and accessories. 872.4120... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4120 Bone cutting instrument and accessories. (a) Identification. A bone cutting instrument and accessories is a metal device intended for use...

  20. 21 CFR 872.4120 - Bone cutting instrument and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Bone cutting instrument and accessories. 872.4120... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4120 Bone cutting instrument and accessories. (a) Identification. A bone cutting instrument and accessories is a metal device intended for use...

  1. 21 CFR 872.4120 - Bone cutting instrument and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Bone cutting instrument and accessories. 872.4120... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4120 Bone cutting instrument and accessories. (a) Identification. A bone cutting instrument and accessories is a metal device intended for use...

  2. 21 CFR 872.4120 - Bone cutting instrument and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Bone cutting instrument and accessories. 872.4120... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Surgical Devices § 872.4120 Bone cutting instrument and accessories. (a) Identification. A bone cutting instrument and accessories is a metal device intended for use...

  3. 21 CFR 872.6640 - Dental operative unit and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Dental operative unit and accessories. 872.6640... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6640 Dental operative unit and accessories. (a) Identification. A dental operative unit and accessories is an AC-powered device that is...

  4. 21 CFR 872.6640 - Dental operative unit and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Dental operative unit and accessories. 872.6640... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6640 Dental operative unit and accessories. (a) Identification. A dental operative unit and accessories is an AC-powered device that is...

  5. 21 CFR 872.6640 - Dental operative unit and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Dental operative unit and accessories. 872.6640... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6640 Dental operative unit and accessories. (a) Identification. A dental operative unit and accessories is an AC-powered device that is...

  6. 21 CFR 872.6640 - Dental operative unit and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Dental operative unit and accessories. 872.6640... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6640 Dental operative unit and accessories. (a) Identification. A dental operative unit and accessories is an AC-powered device that is...

  7. 21 CFR 872.6640 - Dental operative unit and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Dental operative unit and accessories. 872.6640... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6640 Dental operative unit and accessories. (a) Identification. A dental operative unit and accessories is an AC-powered device that is...

  8. Activity Regulates Functional Connectivity from the Vomeronasal Organ to the Accessory Olfactory Bulb

    PubMed Central

    Hovis, Kenneth R.; Ramnath, Rohit; Dahlen, Jeffrey E.; Romanova, Anna L.; LaRocca, Greg; Bier, Mark E.; Urban, Nathaniel N.

    2012-01-01

    The mammalian accessory olfactory system is specialized for the detection of chemicals that identify kin and conspecifics. Vomeronasal sensory neurons (VSNs), residing in the vomeronasal organ, project axons to the accessory olfactory bulb (AOB) where they form synapses with principle neurons, known as mitral cells. The organization of this projection is quite precise and is believed to be essential for appropriate function of this system. However, how this precise connectivity is established is unknown. We show here that in mice the vomeronasal duct is open at birth, allowing external chemical stimuli access to sensory neurons, and that these sensory neurons are capable of releasing neurotransmitter to downstream neurons as early as the first post-natal day. Using major histocompatibility complex class I (MHC-1) peptides to activate a selective subset of VSNs during the first few post-natal days of development, we show that increased activity results in exuberant VSN axonal projections and a delay in axonal coalescence into well-defined glomeruli in the AOB. Finally, we show that mitral cell dendritic refinement occurs just after the coalescence of pre-synaptic axons. Such a mechanism may allow the formation of precise connectivity with specific glomeruli that receive input from sensory neurons expressing the same receptor type. PMID:22674266

  9. 21 CFR 878.3925 - Plastic surgery kit and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Plastic surgery kit and accessories. 878.3925... (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3925 Plastic surgery kit and accessories. (a) Identification. A plastic surgery kit and accessories is a device intended to...

  10. 21 CFR 878.3925 - Plastic surgery kit and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Plastic surgery kit and accessories. 878.3925... (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3925 Plastic surgery kit and accessories. (a) Identification. A plastic surgery kit and accessories is a device intended to...

  11. 21 CFR 878.3925 - Plastic surgery kit and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Plastic surgery kit and accessories. 878.3925... (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3925 Plastic surgery kit and accessories. (a) Identification. A plastic surgery kit and accessories is a device intended to...

  12. 21 CFR 878.3925 - Plastic surgery kit and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Plastic surgery kit and accessories. 878.3925... (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3925 Plastic surgery kit and accessories. (a) Identification. A plastic surgery kit and accessories is a device intended to...

  13. 21 CFR 878.3925 - Plastic surgery kit and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Plastic surgery kit and accessories. 878.3925... (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3925 Plastic surgery kit and accessories. (a) Identification. A plastic surgery kit and accessories is a device intended to...

  14. [Excision of accessory navicular with reconstruction of posterior tibial tendon insertion on navicular for treatment of flatfoot related with accessory navicular].

    PubMed

    Cao, Honghui; Tang, Kanglai; Deng, Yinshuan; Tan, Xiaokang; Zhou, Binghua; Tao, Xu; Chen, Lei; Chen, Qianbo

    2012-06-01

    To analyze the excision of accessory navicular with reconstruction of posterior tibial tendon insertion on navicular for the treatment of flatfoot related with accessory navicular and to evaluate its effectiveness. Between May 2006 and June 2011, 33 patients (40 feet) with flatfoot related with accessory navicular were treated. There were 14 males (17 feet) and 19 females (23 feet) with an average age of 30.1 years (range, 16-56 years). All patients had bilateral accessory navicular; 26 had unilateral flatfoot and 7 had bilateral flatfeet. The disease duration ranged from 7 months to 9 years (median, 24 months). The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-midfoot score was 47.9 +/- 7.3. The X-ray films showed type II accessory navicular, the arch height loss, and heel valgus in all patients. All of them received excision of accessory navicular and reconstruction of posterior tibial tendon insertion on navicular with anchor. All patients got primary wound healing without any complication. Thirty patients (36 feet) were followed up 6-54 months with an average of 23 months. All patients achieved complete pain relief at 6 months after surgery and had good appearance of the feet. The AOFAS ankle-midfoot score was 90.4 +/- 2.0 at last follow-up, showing significant difference when compared with preoperative score (t=29.73, P=0.00). X-ray films showed that no screw loosening or breakage was observed. There were significant differences in the arch height, calcaneus inclination angle, talocalcaneal angle, and talar-first metatarsal angle between pre-operation and last follow-up (P < 0.01). The excision of accessory navicular with reconstruction of posterior tibial tendon insertion on navicular is a good choice for the treatment of flatfoot related with accessory navicular, with correction of deformity, excellent effectiveness, and less complications.

  15. 19 CFR 10.537 - Accessories, spare parts, or tools.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... parts, or tools will be taken into account as originating or non-originating materials, as the case may... 19 Customs Duties 1 2010-04-01 2010-04-01 false Accessories, spare parts, or tools. 10.537 Section... Free Trade Agreement Rules of Origin § 10.537 Accessories, spare parts, or tools. Accessories, spare...

  16. New paradigms in the repair of oxidative damage in human genome: mechanisms ensuring repair of mutagenic base lesions during replication and involvement of accessory proteins.

    PubMed

    Dutta, Arijit; Yang, Chunying; Sengupta, Shiladitya; Mitra, Sankar; Hegde, Muralidhar L

    2015-05-01

    Oxidized bases in the mammalian genome, which are invariably mutagenic due to their mispairing property, are continuously induced by endogenous reactive oxygen species and more abundantly after oxidative stress. Unlike bulky base adducts induced by UV and other environmental mutagens in the genome that block replicative DNA polymerases, oxidatively damaged bases such as 5-hydroxyuracil, produced by oxidative deamination of cytosine in the template strand, do not block replicative polymerases and thus need to be repaired prior to replication to prevent mutation. Following up our earlier studies, which showed that the Nei endonuclease VIII like 1 (NEIL1) DNA glycosylase, one of the five base excision repair (BER)-initiating enzymes in mammalian cells, has enhanced expression during the S-phase and higher affinity for replication fork-mimicking single-stranded (ss) DNA substrates, we recently provided direct experimental evidence for NEIL1's role in replicating template strand repair. The key requirement for this event, which we named as the 'cow-catcher' mechanism of pre-replicative BER, is NEIL1's non-productive binding (substrate binding without product formation) to the lesion base in ss DNA template to stall DNA synthesis, causing fork regression. Repair of the lesion in reannealed duplex is then carried out by NEIL1 in association with the DNA replication proteins. NEIL1 (and other BER-initiating enzymes) also interact with several accessory and non-canonical proteins including the heterogeneous nuclear ribonucleoprotein U and Y-box-binding protein 1 as well as high mobility group box 1 protein, whose precise roles in BER are still obscure. In this review, we have discussed the recent advances in our understanding of oxidative genome damage repair pathways with particular focus on the pre-replicative template strand repair and the role of scaffold factors like X-ray repairs cross-complementing protein 1 and poly (ADP-ribose) polymerase 1 and other accessory

  17. 21 CFR 886.1930 - Tonometer and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1930 Tonometer and accessories. (a) Identification. A tonometer and accessories is a manual device intended to measure intraocular pressure by applying a known force on the globe of the eye and measuring the amount of indentation produced (Schiotz...

  18. 21 CFR 864.3600 - Microscopes and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Microscopes and accessories. 864.3600 Section 864.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3600...

  19. 21 CFR 864.3600 - Microscopes and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Microscopes and accessories. 864.3600 Section 864.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3600...

  20. 21 CFR 864.3600 - Microscopes and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Microscopes and accessories. 864.3600 Section 864.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3600...

  1. 21 CFR 864.3600 - Microscopes and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Microscopes and accessories. 864.3600 Section 864.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3600...

  2. Electronic Position Sensor for Power Operated Accessory

    DOEpatents

    Haag, Ronald H.; Chia, Michael I.

    2005-05-31

    An electronic position sensor for use with a power operated vehicle accessory, such as a power liftgate. The position sensor includes an elongated resistive circuit that is mounted such that it is stationary and extends along the path of a track portion of the power operated accessory. The position sensor further includes a contact nub mounted to a link member that moves within the track portion such that the contact nub is slidingly biased against the elongated circuit. As the link member moves under the force of a motor-driven output gear, the contact nub slides along the surface of the resistive circuit, thereby affecting the overall resistance of the circuit. The position sensor uses the overall resistance to provide an electronic position signal to an ECU, wherein the signal is indicative of the absolute position of the power operated accessory. Accordingly, the electronic position sensor is capable of providing an electronic signal that enables the ECU to track the absolute position of the power operated accessory.

  3. 21 CFR 878.1800 - Speculum and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Speculum and accessories. 878.1800 Section 878.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Diagnostic Devices § 878.1800 Speculum and accessories...

  4. 21 CFR 878.1800 - Speculum and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Speculum and accessories. 878.1800 Section 878.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Diagnostic Devices § 878.1800 Speculum and accessories...

  5. 21 CFR 878.1800 - Speculum and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Speculum and accessories. 878.1800 Section 878.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Diagnostic Devices § 878.1800 Speculum and accessories...

  6. 21 CFR 878.1800 - Speculum and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Speculum and accessories. 878.1800 Section 878.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Diagnostic Devices § 878.1800 Speculum and accessories...

  7. 21 CFR 878.1800 - Speculum and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Speculum and accessories. 878.1800 Section 878.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Diagnostic Devices § 878.1800 Speculum and accessories...

  8. Expression of accessory colonization factor subunit A (ACFA) of Vibrio cholerae and ACFA fused to cholera toxin B subunit in transgenic tomato (Solanum lycopersicum).

    PubMed

    Sharma, Manoj Kumar; Jani, Dewal; Thungapathra, M; Gautam, J K; Meena, L S; Singh, Yogendra; Ghosh, Amit; Tyagi, Akhilesh Kumar; Sharma, Arun Kumar

    2008-05-20

    In earlier study from our group, cholera toxin B subunit had been expressed in tomato for developing a plant-based vaccine against cholera. In the present investigation, gene for accessory colonization factor (acf) subunit A, earlier reported to be essential for efficient colonization in the intestine, has been expressed in Escherichia coli as well as tomato plants. Gene encoding for a chimeric protein having a fusion of cholera toxin B subunit and accessory colonization factor A was also expressed in tomato to generate more potent combinatorial antigen. CaMV35S promoter with a duplicated enhancer sequence was used for expression of these genes in tomato. Integration of transgenes into tomato genome was confirmed by PCR and Southern hybridization. Expression of the genes was confirmed at transcript and protein levels. Accessory colonization factor A and cholera toxin B subunit fused to this protein accumulated up to 0.25% and 0.08% of total soluble protein, respectively, in the fruits of transgenic plants. Whereas protein purified from E. coli, in combination with cholera toxin B subunit can be used for development of conventional subunit vaccine, tomato fruits expressing these proteins can be used together with tomato plants expressing cholera toxin B subunit for development of oral vaccine against cholera.

  9. Manual versus automated methods for cleaning reusable accessory devices used for minimally invasive surgical procedures.

    PubMed

    Alfa, M J; Nemes, R

    2004-09-01

    We undertook a simulated-use study using quantitative methods to evaluate the cleaning efficacy of ported and non-ported accessory devices used in minimally invasive surgery. We chose laparoscopic scissors and forceps to represent worst-case devices which were inoculated with artificial test soil containing 10(6) cfu/mL Enterococcus faecalis and Geobacillus stearothermophilus and allowed to dry for 1 h. Cleaning was performed manually, as well as by the automated SI-Auto Narrow lumen cleaner. Manual cleaning left two- to 50-fold more soil residuals (protein, haemoglobin and carbohydrate) inside the lumen of non-ported versus ported laparoscopic accessory devices. The SI-Auto Narrow lumen cleaner was more efficient than manual cleaning and achieved >99% reduction in soil parameters in both non-ported (using retro-flushing) and ported laparoscopic devices. Only the automated cleaning of ported devices achieved 10(3)-10(4)-fold reduction in bacterial numbers. Sonication alone (no flushing of inner channel) did not effectively remove soil or organisms from the inner channel. Our findings indicate that non-ported accessory devices cannot be as reliably cleaned as ported devices regardless of the cleaning method used. If non-ported accessory devices are reprocessed, they should be cleaned using retro-flushing in an automated narrow lumen cleaner.

  10. BAR domain proteins regulate Rho GTPase signaling.

    PubMed

    Aspenström, Pontus

    2014-01-01

    BAR proteins comprise a heterogeneous group of multi-domain proteins with diverse biological functions. The common denominator is the Bin-Amphiphysin-Rvs (BAR) domain that not only confers targeting to lipid bilayers, but also provides scaffolding to mold lipid membranes into concave or convex surfaces. This function of BAR proteins is an important determinant in the dynamic reconstruction of membrane vesicles, as well as of the plasma membrane. Several BAR proteins function as linkers between cytoskeletal regulation and membrane dynamics. These links are provided by direct interactions between BAR proteins and actin-nucleation-promoting factors of the Wiskott-Aldrich syndrome protein family and the Diaphanous-related formins. The Rho GTPases are key factors for orchestration of this intricate interplay. This review describes how BAR proteins regulate the activity of Rho GTPases, as well as how Rho GTPases regulate the function of BAR proteins. This mutual collaboration is a central factor in the regulation of vital cellular processes, such as cell migration, cytokinesis, intracellular transport, endocytosis, and exocytosis.

  11. Controlled Speed Accessory Drive demonstration program

    NASA Technical Reports Server (NTRS)

    Hoehn, F. W.

    1981-01-01

    A Controlled Speed Accessory Drive System was examined in an effort to improve the fuel economy of passenger cars. Concept feasibility and the performance of a typical system during actual road driving conditions were demonstrated. The CSAD system is described as a mechanical device which limits engine accessory speeds, thereby reducing parasitic horsepower losses and improving overall vehicle fuel economy. Fuel consumption data were compiled for fleets of GSA vehicles. Various motor pool locations were selected, each representing different climatic conditions. On the basis of a total accumulated fleet usage of nearly three million miles, an overall fuel economy improvement of 6 percent to 7 percent was demonstrated. Coincident chassis dynamometer tests were accomplished on selected vehicles to establish the effect of different accessory drive systems on exhaust emissions, and to evaluate the magnitude of the mileage benefits which could be derived.

  12. Accessory stimulus modulates executive function during stepping task

    PubMed Central

    Watanabe, Tatsunori; Koyama, Soichiro; Tanabe, Shigeo

    2015-01-01

    When multiple sensory modalities are simultaneously presented, reaction time can be reduced while interference enlarges. The purpose of this research was to examine the effects of task-irrelevant acoustic accessory stimuli simultaneously presented with visual imperative stimuli on executive function during stepping. Executive functions were assessed by analyzing temporal events and errors in the initial weight transfer of the postural responses prior to a step (anticipatory postural adjustment errors). Eleven healthy young adults stepped forward in response to a visual stimulus. We applied a choice reaction time task and the Simon task, which consisted of congruent and incongruent conditions. Accessory stimuli were randomly presented with the visual stimuli. Compared with trials without accessory stimuli, the anticipatory postural adjustment error rates were higher in trials with accessory stimuli in the incongruent condition and the reaction times were shorter in trials with accessory stimuli in all the task conditions. Analyses after division of trials according to whether anticipatory postural adjustment error occurred or not revealed that the reaction times of trials with anticipatory postural adjustment errors were reduced more than those of trials without anticipatory postural adjustment errors in the incongruent condition. These results suggest that accessory stimuli modulate the initial motor programming of stepping by lowering decision threshold and exclusively under spatial incompatibility facilitate automatic response activation. The present findings advance the knowledge of intersensory judgment processes during stepping and may aid in the development of intervention and evaluation tools for individuals at risk of falls. PMID:25925321

  13. Evidence for a cysteine-mediated mechanism of excitation energy regulation in a photosynthetic antenna complex

    PubMed Central

    Orf, Gregory S.; Saer, Rafael G.; Niedzwiedzki, Dariusz M.; Zhang, Hao; McIntosh, Chelsea L.; Schultz, Jason W.; Mirica, Liviu M.; Blankenship, Robert E.

    2016-01-01

    Light-harvesting antenna complexes not only aid in the capture of solar energy for photosynthesis, but regulate the quantity of transferred energy as well. Light-harvesting regulation is important for protecting reaction center complexes from overexcitation, generation of reactive oxygen species, and metabolic overload. Usually, this regulation is controlled by the association of light-harvesting antennas with accessory quenchers such as carotenoids. One antenna complex, the Fenna–Matthews–Olson (FMO) antenna protein from green sulfur bacteria, completely lacks carotenoids and other known accessory quenchers. Nonetheless, the FMO protein is able to quench energy transfer in aerobic conditions effectively, indicating a previously unidentified type of regulatory mechanism. Through de novo sequencing MS, chemical modification, and mutagenesis, we have pinpointed the source of the quenching action to cysteine residues (Cys49 and Cys353) situated near two low-energy bacteriochlorophylls in the FMO protein from Chlorobaculum tepidum. Removal of these cysteines (particularly removal of the completely conserved Cys353) through N-ethylmaleimide modification or mutagenesis to alanine abolishes the aerobic quenching effect. Electrochemical analysis and electron paramagnetic resonance spectra suggest that in aerobic conditions the cysteine thiols are converted to thiyl radicals which then are capable of quenching bacteriochlorophyll excited states through electron transfer photochemistry. This simple mechanism has implications for the design of bio-inspired light-harvesting antennas and the redesign of natural photosynthetic systems. PMID:27335466

  14. Regulation, Signaling, and Physiological Functions of G-Proteins.

    PubMed

    Syrovatkina, Viktoriya; Alegre, Kamela O; Dey, Raja; Huang, Xin-Yun

    2016-09-25

    Heterotrimeric guanine-nucleotide-binding regulatory proteins (G-proteins) mainly relay the information from G-protein-coupled receptors (GPCRs) on the plasma membrane to the inside of cells to regulate various biochemical functions. Depending on the targeted cell types, tissues, and organs, these signals modulate diverse physiological functions. The basic schemes of heterotrimeric G-proteins have been outlined. In this review, we briefly summarize what is known about the regulation, signaling, and physiological functions of G-proteins. We then focus on a few less explored areas such as the regulation of G-proteins by non-GPCRs and the physiological functions of G-proteins that cannot be easily explained by the known G-protein signaling pathways. There are new signaling pathways and physiological functions for G-proteins to be discovered and further interrogated. With the advancements in structural and computational biological techniques, we are closer to having a better understanding of how G-proteins are regulated and of the specificity of G-protein interactions with their regulators. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. The Core and Accessory Genomes of Burkholderia pseudomallei: Implications for Human Melioidosis

    PubMed Central

    Lin, Chi Ho; Karuturi, R. Krishna M.; Wuthiekanun, Vanaporn; Tuanyok, Apichai; Chua, Hui Hoon; Ong, Catherine; Paramalingam, Sivalingam Suppiah; Tan, Gladys; Tang, Lynn; Lau, Gary; Ooi, Eng Eong; Woods, Donald; Feil, Edward; Peacock, Sharon J.; Tan, Patrick

    2008-01-01

    Natural isolates of Burkholderia pseudomallei (Bp), the causative agent of melioidosis, can exhibit significant ecological flexibility that is likely reflective of a dynamic genome. Using whole-genome Bp microarrays, we examined patterns of gene presence and absence across 94 South East Asian strains isolated from a variety of clinical, environmental, or animal sources. 86% of the Bp K96243 reference genome was common to all the strains representing the Bp “core genome”, comprising genes largely involved in essential functions (eg amino acid metabolism, protein translation). In contrast, 14% of the K96243 genome was variably present across the isolates. This Bp accessory genome encompassed multiple genomic islands (GIs), paralogous genes, and insertions/deletions, including three distinct lipopolysaccharide (LPS)-related gene clusters. Strikingly, strains recovered from cases of human melioidosis clustered on a tree based on accessory gene content, and were significantly more likely to harbor certain GIs compared to animal and environmental isolates. Consistent with the inference that the GIs may contribute to pathogenesis, experimental mutation of BPSS2053, a GI gene, reduced microbial adherence to human epithelial cells. Our results suggest that the Bp accessory genome is likely to play an important role in microbial adaptation and virulence. PMID:18927621

  16. 14 CFR 23.1437 - Accessories for multiengine airplanes.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Accessories for multiengine airplanes. 23... TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Equipment Miscellaneous Equipment § 23.1437 Accessories for multiengine airplanes. For multiengine airplanes...

  17. 14 CFR 23.1437 - Accessories for multiengine airplanes.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Accessories for multiengine airplanes. 23... TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Equipment Miscellaneous Equipment § 23.1437 Accessories for multiengine airplanes. For multiengine airplanes...

  18. 14 CFR 23.1437 - Accessories for multiengine airplanes.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Accessories for multiengine airplanes. 23... TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Equipment Miscellaneous Equipment § 23.1437 Accessories for multiengine airplanes. For multiengine airplanes...

  19. Evidence for an allosteric mechanism of substrate release from membrane-transporter accessory binding proteins.

    PubMed

    Marinelli, Fabrizio; Kuhlmann, Sonja I; Grell, Ernst; Kunte, Hans-Jörg; Ziegler, Christine; Faraldo-Gómez, José D

    2011-12-06

    Numerous membrane importers rely on accessory water-soluble proteins to capture their substrates. These substrate-binding proteins (SBP) have a strong affinity for their ligands; yet, substrate release onto the low-affinity membrane transporter must occur for uptake to proceed. It is generally accepted that release is facilitated by the association of SBP and transporter, upon which the SBP adopts a conformation similar to the unliganded state, whose affinity is sufficiently reduced. Despite the appeal of this mechanism, however, direct supporting evidence is lacking. Here, we use experimental and theoretical methods to demonstrate that an allosteric mechanism of enhanced substrate release is indeed plausible. First, we report the atomic-resolution structure of apo TeaA, the SBP of the Na(+)-coupled ectoine TRAP transporter TeaBC from Halomonas elongata DSM2581(T), and compare it with the substrate-bound structure previously reported. Conformational free-energy landscape calculations based upon molecular dynamics simulations are then used to dissect the mechanism that couples ectoine binding to structural change in TeaA. These insights allow us to design a triple mutation that biases TeaA toward apo-like conformations without directly perturbing the binding cleft, thus mimicking the influence of the membrane transporter. Calorimetric measurements demonstrate that the ectoine affinity of the conformationally biased triple mutant is 100-fold weaker than that of the wild type. By contrast, a control mutant predicted to be conformationally unbiased displays wild-type affinity. This work thus demonstrates that substrate release from SBPs onto their membrane transporters can be facilitated by the latter through a mechanism of allosteric modulation of the former.

  20. Anesthesiology Devices; Reclassification of Membrane Lung for Long-Term Pulmonary Support; Redesignation as Extracorporeal Circuit and Accessories for Long-Term Respiratory/Cardiopulmonary Failure. Final order.

    PubMed

    2016-02-12

    The Food and Drug Administration (FDA) is issuing a final order to redesignate membrane lung devices for long-term pulmonary support, a preamendments class III device, as extracorporeal circuit and accessories for long-term respiratory/cardiopulmonary failure, and to reclassify the device to class II (special controls) in patients with acute respiratory failure or acute cardiopulmonary failure where other available treatment options have failed, and continued clinical deterioration is expected or the risk of death is imminent. A membrane lung device for long-term pulmonary support (>6 hours) refers to the oxygenator in an extracorporeal circuit used during long-term procedures, commonly referred to as extracorporeal membrane oxygenation (ECMO). Because a number of other devices and accessories are used with the oxygenator in the circuit, the title and identification of the regulation are revised to include extracorporeal circuit and accessories for long-term respiratory/cardiopulmonary failure. Although an individual device or accessory used in an ECMO circuit may already have its own classification regulation when the device or accessory is intended for short-term use (<=6 hours), such device or accessory will be subject to the same regulatory controls applied to the oxygenator (i.e., class II, special controls) when evaluated as part of the ECMO circuit for long-term use (>6 hours). On its own initiative, based on new information, FDA is revising the classification of the membrane lung device for long-term pulmonary support.

  1. Thioredoxin-interacting protein regulates protein disulfide isomerases and endoplasmic reticulum stress.

    PubMed

    Lee, Samuel; Min Kim, Soo; Dotimas, James; Li, Letitia; Feener, Edward P; Baldus, Stephan; Myers, Ronald B; Chutkow, William A; Patwari, Parth; Yoshioka, Jun; Lee, Richard T

    2014-06-01

    The endoplasmic reticulum (ER) is responsible for protein folding, modification, and trafficking. Accumulation of unfolded or misfolded proteins represents the condition of ER stress and triggers the unfolded protein response (UPR), a key mechanism linking supply of excess nutrients to insulin resistance and type 2 diabetes in obesity. The ER harbors proteins that participate in protein folding including protein disulfide isomerases (PDIs). Changes in PDI activity are associated with protein misfolding and ER stress. Here, we show that thioredoxin-interacting protein (Txnip), a member of the arrestin protein superfamily and one of the most strongly induced proteins in diabetic patients, regulates PDI activity and UPR signaling. We found that Txnip binds to PDIs and increases their enzymatic activity. Genetic deletion of Txnip in cells and mice led to increased protein ubiquitination and splicing of the UPR regulated transcription factor X-box-binding protein 1 (Xbp1s) at baseline as well as under ER stress. Our results reveal Txnip as a novel direct regulator of PDI activity and a feedback mechanism of UPR signaling to decrease ER stress. © 2014 Brigham and Women's Hospital. Published under the terms of the CC BY 4.0 license.

  2. 21 CFR 876.5820 - Hemodialysis system and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... (1) The extracorporeal blood system and accessories consists of tubing, pumps, pressure monitors, air... conditions and that consists of an extracorporeal blood system, a conventional dialyzer, a dialysate delivery system, and accessories. Blood from a patient flows through the tubing of the extracorporeal blood system...

  3. 21 CFR 876.5820 - Hemodialysis system and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... (1) The extracorporeal blood system and accessories consists of tubing, pumps, pressure monitors, air... conditions and that consists of an extracorporeal blood system, a conventional dialyzer, a dialysate delivery system, and accessories. Blood from a patient flows through the tubing of the extracorporeal blood system...

  4. 21 CFR 876.5820 - Hemodialysis system and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... (1) The extracorporeal blood system and accessories consists of tubing, pumps, pressure monitors, air... conditions and that consists of an extracorporeal blood system, a conventional dialyzer, a dialysate delivery system, and accessories. Blood from a patient flows through the tubing of the extracorporeal blood system...

  5. 21 CFR 876.5820 - Hemodialysis system and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... (1) The extracorporeal blood system and accessories consists of tubing, pumps, pressure monitors, air... conditions and that consists of an extracorporeal blood system, a conventional dialyzer, a dialysate delivery system, and accessories. Blood from a patient flows through the tubing of the extracorporeal blood system...

  6. 14 CFR 23.1437 - Accessories for multiengine airplanes.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Accessories for multiengine airplanes. 23.1437 Section 23.1437 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF..., engine-driven accessories essential to safe operation must be distributed among two or more engines so...

  7. 14 CFR 23.1437 - Accessories for multiengine airplanes.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Accessories for multiengine airplanes. 23.1437 Section 23.1437 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF..., engine-driven accessories essential to safe operation must be distributed among two or more engines so...

  8. A left lateral accessory pathway unmasked by rivastigmine.

    PubMed

    Guenancia, Charles; Fichot, Marie; Garnier, Fabien; Montoy, Mathieu; Laurent, Gabriel

    A 75-year-old woman was referred for advice regarding surface electrocardiographic modifications after the initiation of rivastigmine. In our patient, the baseline ECGs appeared perfectly normal. However, the initiation of a cholinesterase inhibitor unmasked a left lateral accessory pathway that had never been diagnosed before. Although cholinesterase inhibitors are known to increase vagal tone, the PR interval was shortened after rivastigmine administration, thus excluding this hypothesis to explain the appearance of the accessory pathway. Therefore, we hypothesized that cholinesterase inhibitors may have increased conduction velocity in the accessory pathway or in the atria. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. 21 CFR 884.5350 - Contraceptive diaphragm and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Contraceptive diaphragm and accessories. 884.5350 Section 884.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Devices § 884.5350 Contraceptive diaphragm and accessories. (a) Identification. A contraceptive diaphragm...

  10. 21 CFR 884.5350 - Contraceptive diaphragm and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Contraceptive diaphragm and accessories. 884.5350 Section 884.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Devices § 884.5350 Contraceptive diaphragm and accessories. (a) Identification. A contraceptive diaphragm...

  11. 21 CFR 884.5350 - Contraceptive diaphragm and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Contraceptive diaphragm and accessories. 884.5350 Section 884.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Devices § 884.5350 Contraceptive diaphragm and accessories. (a) Identification. A contraceptive diaphragm...

  12. 21 CFR 884.5350 - Contraceptive diaphragm and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Contraceptive diaphragm and accessories. 884.5350 Section 884.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Devices § 884.5350 Contraceptive diaphragm and accessories. (a) Identification. A contraceptive diaphragm...

  13. 21 CFR 884.5350 - Contraceptive diaphragm and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Contraceptive diaphragm and accessories. 884.5350 Section 884.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Devices § 884.5350 Contraceptive diaphragm and accessories. (a) Identification. A contraceptive diaphragm...

  14. The accessory gene regulator (agr) controls Staphylococcus aureus virulence in a murine intracranial abscesses model.

    PubMed

    Gong, Jian; Li, Dongzhi; Yan, Jun; Liu, Yu; Li, Di; Dong, Jie; Gao, Yaping; Sun, Tao; Yang, Guang

    2014-01-01

    Intracranial abscesses are associated with high mortality. Staphylococcus aureus is one of the main pathogens that cause intracranial infection. Until now, there is no report to identify the key effectors of S. aureus during the intracranial infection. The murine intracranial abscesses model induced by S. aureus was constructed. The vital sign and survival rate of mice were observed to evaluate the infection. Histological examination was used to diagnose the pathological alterations of mouse tissues. The sensitivity of S. aureus to whole blood was evaluated by whole-blood killing assay. In murine intracranial abscesses model, it was shown that the mortality caused by the accessory gene regulator (agr) locus deficient strain was significant decreased compared with its parent strain. Moreover, we found that RNAIII, the effector of agr system, was essential for the intracranial infection caused by S. aureus. In the further investigation, it was shown that restoration the expression of α-toxin in agr deficient strain could partially recover the mortality in the murine intracranial abscesses model. Our data suggested that the agr system of S. aureus is an important virulence determinant in the induction and mortality of intracranial abscesses in mice. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

  15. Analysis of a Soluble (UreD:UreF:UreG)2 Accessory Protein Complex and its Interactions with Klebsiella aerogenes Urease by Mass Spectrometry

    PubMed Central

    Farrugia, Mark A.; Han, Linjie; Zhong, Yueyang; Boer, Jodi L.; Ruotolo, Brandon T.; Hausinger, Robert P.

    2013-01-01

    Maturation of the nickel-containing urease of Klebsiella aerogenes is facilitated by the UreD, UreF, and UreG accessory proteins along with the UreE metallo-chaperone. A fusion of the maltose binding protein and UreD (MBP-UreD) was co-isolated with UreF and UreG in a soluble complex possessing a (MBP-UreD:UreF:UreG)2 quaternary structure. Within this complex a UreF:UreF interaction was identified by chemical cross-linking of the amino termini of its two UreF protomers, as shown by mass spectrometry of tryptic peptides. A pre-activation complex was formed by the interaction of (MBP-UreD:UreF:UreG)2 and urease. Mass spectrometry of intact protein species revealed a pathway for synthesis of the urease pre-activation complex in which individual hetero-trimer units of the (MBP-UreD:UreF:UreG)2 complex bind to urease. Together, these data provide important new insights into the structures of protein complexes associated with urease activation. PMID:23797863

  16. Analysis of a Soluble (UreD:UreF:UreG)2 Accessory Protein Complex and Its Interactions with Klebsiella aerogenes Urease by Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Farrugia, Mark A.; Han, Linjie; Zhong, Yueyang; Boer, Jodi L.; Ruotolo, Brandon T.; Hausinger, Robert P.

    2013-09-01

    Maturation of the nickel-containing urease of Klebsiella aerogenes is facilitated by the UreD, UreF, and UreG accessory proteins along with the UreE metallo-chaperone. A fusion of the maltose binding protein and UreD (MBP-UreD) was co-isolated with UreF and UreG in a soluble complex possessing a (MBP-UreD:UreF:UreG)2 quaternary structure. Within this complex a UreF:UreF interaction was identified by chemical cross-linking of the amino termini of its two UreF protomers, as shown by mass spectrometry of tryptic peptides. A pre-activation complex was formed by the interaction of (MBP-UreD:UreF:UreG)2 and urease. Mass spectrometry of intact protein species revealed a pathway for synthesis of the urease pre-activation complex in which individual hetero-trimer units of the (MBP-UreD:UreF:UreG)2 complex bind to urease. Together, these data provide important new insights into the structures of protein complexes associated with urease activation.

  17. 21 CFR 884.4120 - Gynecologic electrocautery and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Gynecologic electrocautery and accessories. 884.4120 Section 884.4120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... under direct visual observation. This generic type of device may include the following accessories: an...

  18. 14 CFR 23.1192 - Engine accessory compartment diaphragm.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Engine accessory compartment diaphragm. 23... Powerplant Powerplant Fire Protection § 23.1192 Engine accessory compartment diaphragm. For aircooled radial engines, the engine power section and all portions of the exhaust sytem must be isolated from the engine...

  19. 14 CFR 23.1192 - Engine accessory compartment diaphragm.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Engine accessory compartment diaphragm. 23... Powerplant Powerplant Fire Protection § 23.1192 Engine accessory compartment diaphragm. For aircooled radial engines, the engine power section and all portions of the exhaust sytem must be isolated from the engine...

  20. 14 CFR 23.1192 - Engine accessory compartment diaphragm.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Engine accessory compartment diaphragm. 23... Powerplant Powerplant Fire Protection § 23.1192 Engine accessory compartment diaphragm. For aircooled radial engines, the engine power section and all portions of the exhaust sytem must be isolated from the engine...

  1. 21 CFR 876.4890 - Urological table and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., stirrups, and belts used to support a patient in a suitable position for endoscopic procedures of the lower...) Class II (special controls) for the electrically powered urological table and accessories. The device is... § 876.9. (2) Class I for the manually powered table and accessories, and for stirrups for electrically...

  2. Functional analysis of human foamy virus accessory reading frames.

    PubMed Central

    Baunach, G; Maurer, B; Hahn, H; Kranz, M; Rethwilm, A

    1993-01-01

    Foamy viruses belong to the retroviruses which possess a complex genome structure. The human foamy virus (HFV) isolate bears three open reading frames (the so-called bel genes) in the 3' region of the genome which have been reported to give rise to possibly six different proteins via alternative splicing (W. Muranyi and R. M. Flügel, J. Virol. 65:727-735, 1991). In order to analyze the requirements of these proteins for HFV replication in vitro, we constructed a set of single and combinatory bel gene mutants of an infectious molecular clone of HFV. The mutant which lacked the transacting activator, bel-1, was found to be replication incompetent. All other mutants replicated equally well and gave rise to comparable titers of infectious cell-free virus. When HFV proviruses were put under the control of a heterologous promoter (simian virus 40), none of the accessory gene products was found to be required for expression of structural (gag) proteins. There was no evidence for a posttranscriptional regulatory protein that is present in other complex retroviruses. Images PMID:8394455

  3. 15 CFR 742.11 - Specially designed implements of torture, thumbscrews, and thumbcuffs; and parts and accessories...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Specially designed implements of torture, thumbscrews, and thumbcuffs; and parts and accessories, n.e.s. 742.11 Section 742.11 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND...

  4. 14 CFR 125.149 - Engine accessory section diaphragm.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Engine accessory section diaphragm. 125.149... Requirements § 125.149 Engine accessory section diaphragm. Unless equivalent protection can be shown by other means, a diaphragm that complies with § 125.145 must be provided on air-cooled engines to isolate the...

  5. 14 CFR 125.149 - Engine accessory section diaphragm.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Engine accessory section diaphragm. 125.149... Requirements § 125.149 Engine accessory section diaphragm. Unless equivalent protection can be shown by other means, a diaphragm that complies with § 125.145 must be provided on air-cooled engines to isolate the...

  6. 14 CFR 125.149 - Engine accessory section diaphragm.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Engine accessory section diaphragm. 125.149... Requirements § 125.149 Engine accessory section diaphragm. Unless equivalent protection can be shown by other means, a diaphragm that complies with § 125.145 must be provided on air-cooled engines to isolate the...

  7. 14 CFR 125.149 - Engine accessory section diaphragm.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Engine accessory section diaphragm. 125.149... Requirements § 125.149 Engine accessory section diaphragm. Unless equivalent protection can be shown by other means, a diaphragm that complies with § 125.145 must be provided on air-cooled engines to isolate the...

  8. Wrecked regulation of intrinsically disordered proteins in diseases: pathogenicity of deregulated regulators

    PubMed Central

    Uversky, Vladimir N.

    2014-01-01

    Biologically active proteins without stable tertiary structure are common in all known proteomes. Functions of these intrinsically disordered proteins (IDPs) are typically related to regulation, signaling, and control. Cellular levels of these important regulators are tightly regulated by a variety mechanisms ranging from firmly controlled expression to precisely targeted degradation. Functions of IDPs are controlled by binding to specific partners, alternative splicing, and posttranslational modifications among other means. In the norm, right amounts of precisely activated IDPs have to be present in right time at right places. Wrecked regulation brings havoc to the ordered world of disordered proteins, leading to protein misfolding, misidentification, and missignaling that give rise to numerous human diseases, such as cancer, cardiovascular disease, neurodegenerative diseases, and diabetes. Among factors inducing pathogenic transformations of IDPs are various cellular mechanisms, such as chromosomal translocations, damaged splicing, altered expression, frustrated posttranslational modifications, aberrant proteolytic degradation, and defective trafficking. This review presents some of the aspects of deregulated regulation of IDPs leading to human diseases. PMID:25988147

  9. Mechanism of Selective Nickel Transfer from HypB to HypA, Escherichia coli [NiFe]-Hydrogenase Accessory Proteins.

    PubMed

    Lacasse, Michael J; Douglas, Colin D; Zamble, Deborah B

    2016-12-13

    [NiFe]-hydrogenase enzymes catalyze the reversible reduction of protons to molecular hydrogen and serve as a vital component of the metabolism of many pathogens. The synthesis of the bimetallic catalytic center requires a suite of accessory proteins, and the penultimate step, nickel insertion, is facilitated by the metallochaperones HypA and HypB. In Escherichia coli, nickel moves from a site in the GTPase domain of HypB to HypA in a process accelerated by GDP. To determine how the transfer of nickel is controlled, the impacts of HypA and nucleotides on the properties of HypB were examined. Integral to this work was His2Gln HypA, a mutant with attenuated nickel affinity that does not support hydrogenase production in E. coli. This mutation inhibits the translocation of nickel from HypB. H2Q-HypA does not modulate the apparent metal affinity of HypB, but the stoichiometry and stability of the HypB-nickel complex are modulated by the nucleotide. Furthermore, the HypA-HypB interaction was detected by gel filtration chromatography if HypB was loaded with GDP, but not a GTP analogue, and the protein complex dissociated upon binding of nickel to His2 of HypA. In contrast, a nucleotide does not modulate the binding of zinc to HypB, and loading zinc into the GTPase domain of HypB inhibits formation of the complex with HypA. These results demonstrate that GTP hydrolysis controls both metal binding and protein-protein interactions, conferring selective and directional nickel transfer during [NiFe]-hydrogenase biosynthesis.

  10. Intraspecies Competition in Serratia marcescens Is Mediated by Type VI-Secreted Rhs Effectors and a Conserved Effector-Associated Accessory Protein

    PubMed Central

    Alcoforado Diniz, Juliana

    2015-01-01

    ABSTRACT The type VI secretion system (T6SS) is widespread in Gram-negative bacteria and can deliver toxic effector proteins into eukaryotic cells or competitor bacteria. Antibacterial T6SSs are increasingly recognized as key mediators of interbacterial competition and may contribute to the outcome of many polymicrobial infections. Multiple antibacterial effectors can be delivered by these systems, with diverse activities against target cells and distinct modes of secretion. Polymorphic toxins containing Rhs repeat domains represent a recently identified and as-yet poorly characterized class of T6SS-dependent effectors. Previous work had revealed that the potent antibacterial T6SS of the opportunistic pathogen Serratia marcescens promotes intraspecies as well as interspecies competition (S. L. Murdoch, K. Trunk, G. English, M. J. Fritsch, E. Pourkarimi, and S. J. Coulthurst, J Bacteriol 193:6057–6069, 2011, http://dx.doi.org/10.1128/JB.05671-11). In this study, two new Rhs family antibacterial effectors delivered by this T6SS have been identified. One of these was shown to act as a DNase toxin, while the other contains a novel, cytoplasmic-acting toxin domain. Importantly, using S. marcescens, it has been demonstrated for the first time that Rhs proteins, rather than other T6SS-secreted effectors, can be the primary determinant of intraspecies competition. Furthermore, a new family of accessory proteins associated with T6SS effectors has been identified, exemplified by S. marcescens EagR1, which is specifically required for deployment of its associated Rhs effector. Together, these findings provide new insight into how bacteria can use the T6SS to deploy Rhs-family effectors and mediate different types of interbacterial interactions. IMPORTANCE Infectious diseases caused by bacterial pathogens represent a continuing threat to health and economic prosperity. To counter this threat, we must understand how such organisms survive and prosper. The type VI secretion

  11. Accessory cells in physiological lymphoid tissue from the intestine: an immunohistochemical study.

    PubMed

    Sarsfield, P; Rinne, A; Jones, D B; Johnson, P; Wright, D H

    1996-03-01

    We report a study of the organization of accessory cell populations, in normal mucosal lymphoid tissue from small intestine (8 cases), large intestine (6) and appendix (9) using a panel of monoclonal antibodies and polyclonal antisera in paraffin-embedded tissue. Two populations were identified in dome areas, one positive for acid cysteine proteinase inhibitor and HLA class II (WR18) only and the second positive for S-100 protein, CD68, and WR18 and negative for acid cysteine proteinase inhibitor and factor XIIIa. Superficial colonic mucosal and small intestinal villous tip macrophages stained positively with CD68 and WR18 only, while deeper cryptal and submucosal populations exhibited additional positivity for factor XIIIa, but both populations were negative for acid cysteine proteinase inhibitor and S-100 protein. Germinal centre macrophages were positive for CD68, WR18 and acid cysteine proteinase inhibitor and negative for factor XIIIa, and S-100 protein. T zone dendritic cells included a population which stained positively for S-100 protien, WR18 and were negative for factor XIIIa, CD68 and acid cysteine proteinase inhibitor, an immunophenotype typical of interdigitating dendritic reticulum cells. This distribution of phenotypically identifiable accessory cell subpopulations was apparent at all three sites examined. We suggest that the specialized subpopulations of dendritic cells staining for S-100 protein and for acid cysteine proteinase inhibitor which are restricted to the dome areas, may have a potential role in the transfer of antigen across the epithelium to the germinal centres, while factor XIIIa appears to identify a tissue macrophage population with a potential role in stromal modulation distant from direct antigen challenge.

  12. Insect heat shock proteins during stress and diapause.

    PubMed

    King, Allison M; MacRae, Thomas H

    2015-01-07

    Insect heat shock proteins include ATP-independent small heat shock proteins and the larger ATP-dependent proteins, Hsp70, Hsp90, and Hsp60. In concert with cochaperones and accessory proteins, heat shock proteins mediate essential activities such as protein folding, localization, and degradation. Heat shock proteins are synthesized constitutively in insects and induced by stressors such as heat, cold, crowding, and anoxia. Synthesis depends on the physiological state of the insect, but the common function of heat shock proteins, often working in networks, is to maintain cell homeostasis through interaction with substrate proteins. Stress-induced expression of heat shock protein genes occurs in a background of protein synthesis inhibition, but in the course of diapause, a state of dormancy and increased stress tolerance, these genes undergo differential regulation without the general disruption of protein production. During diapause, when ATP concentrations are low, heat shock proteins may sequester rather than fold proteins.

  13. 21 CFR 884.2660 - Fetal ultrasonic monitor and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fetal ultrasonic monitor and accessories. 884.2660... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Monitoring Devices § 884.2660 Fetal ultrasonic monitor and accessories. (a) Identification. A fetal ultrasonic...

  14. 21 CFR 884.2660 - Fetal ultrasonic monitor and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Fetal ultrasonic monitor and accessories. 884.2660... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Monitoring Devices § 884.2660 Fetal ultrasonic monitor and accessories. (a) Identification. A fetal ultrasonic...

  15. 21 CFR 884.2660 - Fetal ultrasonic monitor and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fetal ultrasonic monitor and accessories. 884.2660... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Monitoring Devices § 884.2660 Fetal ultrasonic monitor and accessories. (a) Identification. A fetal ultrasonic...

  16. Transcriptional Profiles of Mating-Responsive Genes from Testes and Male Accessory Glands of the Mediterranean Fruit Fly, Ceratitis capitata

    PubMed Central

    Scolari, Francesca; Gomulski, Ludvik M.; Ribeiro, José M. C.; Siciliano, Paolo; Meraldi, Alice; Falchetto, Marco; Bonomi, Angelica; Manni, Mosè; Gabrieli, Paolo; Malovini, Alberto; Bellazzi, Riccardo; Aksoy, Serap; Gasperi, Giuliano; Malacrida, Anna R.

    2012-01-01

    Background Insect seminal fluid is a complex mixture of proteins, carbohydrates and lipids, produced in the male reproductive tract. This seminal fluid is transferred together with the spermatozoa during mating and induces post-mating changes in the female. Molecular characterization of seminal fluid proteins in the Mediterranean fruit fly, Ceratitis capitata, is limited, although studies suggest that some of these proteins are biologically active. Methodology/Principal Findings We report on the functional annotation of 5914 high quality expressed sequence tags (ESTs) from the testes and male accessory glands, to identify transcripts encoding putative secreted peptides that might elicit post-mating responses in females. The ESTs were assembled into 3344 contigs, of which over 33% produced no hits against the nr database, and thus may represent novel or rapidly evolving sequences. Extraction of the coding sequences resulted in a total of 3371 putative peptides. The annotated dataset is available as a hyperlinked spreadsheet. Four hundred peptides were identified with putative secretory activity, including odorant binding proteins, protease inhibitor domain-containing peptides, antigen 5 proteins, mucins, and immunity-related sequences. Quantitative RT-PCR-based analyses of a subset of putative secretory protein-encoding transcripts from accessory glands indicated changes in their abundance after one or more copulations when compared to virgin males of the same age. These changes in abundance, particularly evident after the third mating, may be related to the requirement to replenish proteins to be transferred to the female. Conclusions/Significance We have developed the first large-scale dataset for novel studies on functions and processes associated with the reproductive biology of Ceratitis capitata. The identified genes may help study genome evolution, in light of the high adaptive potential of the medfly. In addition, studies of male recovery dynamics in terms

  17. 21 CFR 874.4680 - Bronchoscope (flexible or rigid) and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (flexible or rigid) and accessories. (a) Identification. A bronchoscope (flexible or rigid) and accessories... bronchoscope and is intended to examine or treat the larynx and tracheobronchial tree. It is typically used...

  18. Accessory mental foramina and nerves: Application to periodontal, periapical, and implant surgery.

    PubMed

    Iwanaga, Joe; Watanabe, Koichi; Saga, Tsuyoshi; Tabira, Yoko; Kitashima, Sadaharu; Kusukawa, Jingo; Yamaki, Koh-Ichi

    2016-05-01

    Recent studies investigating accessory mental foramina using developments in diagnostic imaging have primarily defined the morphology of the foramina; however, few studies have described the structures passing through them. Additional clinical knowledge of the foramina is therefore required for preoperative diagnosis prior to surgery, including implant, periodontal and periapical surgery. In this study, we investigated the accessory mental foramina and the associated nerves and arteries in donated cadaveric mandibles using anatomical and radiological observation methods. We examined 63 mandibles with overlying soft tissue by cone-beam computed tomography and noted the existence of the accessory mental foramina. Mandibles with accessory mental foramina were subsequently analyzed. Additionally, the neurovascular bundles passing through these foramina were dissected using anatomical methods.The incidence of accessory mental foramina was 14.3%. The larger foramina tended to be located anteriorly or superiorly and proximal to the mental foramen, while the smaller foramina tended to be located posterosuperiorly and distal to the mental foramen. The mental foramen ipsilateral to the accessory mental foramen was smaller than the one contralateral to it. The comparatively distant and large accessory mental foramen included an artery.This study elucidated the relationship between accessory mental foramina and the associated nerves and arteries. We believe that the results will contribute to the clinical dentistry field. © 2015 Wiley Periodicals, Inc.

  19. 21 CFR 884.2700 - Intrauterine pressure monitor and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Intrauterine pressure monitor and accessories. 884.2700 Section 884.2700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... include the following accessories: signal analysis and display equipment, patient and equipment supports...

  20. 21 CFR 884.2640 - Fetal phonocardiographic monitor and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Fetal phonocardiographic monitor and accessories. 884.2640 Section 884.2640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... includes the following accessories: signal analysis and display equipment, patient and equipment supports...

  1. 21 CFR 884.2640 - Fetal phonocardiographic monitor and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Fetal phonocardiographic monitor and accessories. 884.2640 Section 884.2640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... includes the following accessories: signal analysis and display equipment, patient and equipment supports...

  2. 21 CFR 884.2700 - Intrauterine pressure monitor and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Intrauterine pressure monitor and accessories. 884.2700 Section 884.2700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... include the following accessories: signal analysis and display equipment, patient and equipment supports...

  3. 21 CFR 884.2640 - Fetal phonocardiographic monitor and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fetal phonocardiographic monitor and accessories. 884.2640 Section 884.2640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... includes the following accessories: signal analysis and display equipment, patient and equipment supports...

  4. 21 CFR 884.2640 - Fetal phonocardiographic monitor and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal phonocardiographic monitor and accessories. 884.2640 Section 884.2640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... includes the following accessories: signal analysis and display equipment, patient and equipment supports...

  5. 21 CFR 884.2640 - Fetal phonocardiographic monitor and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fetal phonocardiographic monitor and accessories. 884.2640 Section 884.2640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... includes the following accessories: signal analysis and display equipment, patient and equipment supports...

  6. 21 CFR 884.2700 - Intrauterine pressure monitor and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Intrauterine pressure monitor and accessories. 884.2700 Section 884.2700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... include the following accessories: signal analysis and display equipment, patient and equipment supports...

  7. Complete Spinal Accessory Nerve Palsy From Carrying Climbing Gear.

    PubMed

    Coulter, Jess M; Warme, Winston J

    2015-09-01

    We report an unusual case of spinal accessory nerve palsy sustained while transporting climbing gear. Spinal accessory nerve injury is commonly a result of iatrogenic surgical trauma during lymph node excision. This particular nerve is less frequently injured by blunt trauma. The case reported here results from compression of the spinal accessory nerve for a sustained period-that is, carrying a load over the shoulder using a single nylon rope for 2.5 hours. This highlights the importance of using proper load-carrying equipment to distribute weight over a greater surface area to avoid nerve compression in the posterior triangle of the neck. The signs and symptoms of spinal accessory nerve palsy and its etiology are discussed. This report is particularly relevant to individuals involved in mountaineering and rock climbing but can be extended to anyone carrying a load with a strap over one shoulder and across the body. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  8. Regulation of protease-activated receptor 1 signaling by the adaptor protein complex 2 and R4 subfamily of regulator of G protein signaling proteins.

    PubMed

    Chen, Buxin; Siderovski, David P; Neubig, Richard R; Lawson, Mark A; Trejo, Joann

    2014-01-17

    The G protein-coupled protease-activated receptor 1 (PAR1) is irreversibly proteolytically activated by thrombin. Hence, the precise regulation of PAR1 signaling is important for proper cellular responses. In addition to desensitization, internalization and lysosomal sorting of activated PAR1 are critical for the termination of signaling. Unlike most G protein-coupled receptors, PAR1 internalization is mediated by the clathrin adaptor protein complex 2 (AP-2) and epsin-1, rather than β-arrestins. However, the function of AP-2 and epsin-1 in the regulation of PAR1 signaling is not known. Here, we report that AP-2, and not epsin-1, regulates activated PAR1-stimulated phosphoinositide hydrolysis via two different mechanisms that involve, in part, a subset of R4 subfamily of "regulator of G protein signaling" (RGS) proteins. A significantly greater increase in activated PAR1 signaling was observed in cells depleted of AP-2 using siRNA or in cells expressing a PAR1 (420)AKKAA(424) mutant with defective AP-2 binding. This effect was attributed to AP-2 modulation of PAR1 surface expression and efficiency of G protein coupling. We further found that ectopic expression of R4 subfamily members RGS2, RGS3, RGS4, and RGS5 reduced activated PAR1 wild-type signaling, whereas signaling by the PAR1 AKKAA mutant was minimally affected. Intriguingly, siRNA-mediated depletion analysis revealed a function for RGS5 in the regulation of signaling by the PAR1 wild type but not the AKKAA mutant. Moreover, activation of the PAR1 wild type, and not the AKKAA mutant, induced Gαq association with RGS3 via an AP-2-dependent mechanism. Thus, AP-2 regulates activated PAR1 signaling by altering receptor surface expression and through recruitment of RGS proteins.

  9. 19 CFR 10.2020 - Accessories, spare parts, or tools.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Accessories, spare parts, or tools. 10.2020 Section 10.2020 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... Trade Promotion Agreement Rules of Origin § 10.2020 Accessories, spare parts, or tools. (a) General...

  10. 19 CFR 10.600 - Accessories, spare parts, or tools.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...-Central America-United States Free Trade Agreement Rules of Origin § 10.600 Accessories, spare parts, or... 10.600 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... of the good's standard accessories, spare parts, or tools will be treated as originating goods if the...

  11. Accessory neuropathy after sternotomy: Clinico-anatomical correlation supporting an inflammatory cause.

    PubMed

    Kassem, Mohammad W; Iwanaga, Joe; Loukas, Marios; Stone, Jonathan J; Smith, Jay; Spinner, Robert J; Tubbs, R Shane

    2018-04-01

    Inflammatory etiologies are becoming increasingly recognized as explanations of some neuropathies, especially those occurring in the perioperative period. Although "brachial neuritis" is known to affect extraplexal nerves, accessory nerve palsy following median sternotomy has been attributed to stretch on the nerve. To better elucidate stretch as a potential cause, a cadaveric study was performed. Two patients who developed accessory nerve palsy following median sternotomy are presented to illustrate features consistent with the diagnosis of a perioperative inflammatory neuropathy. Five adult unembalmed cadavers underwent exposure of the bilateral accessory nerves in the posterior cervical triangle. A median sternotomy was performed and self-retaining retractors positioned. With the head in neutral, left rotation and right rotation, retractors were opened as during surgery while observing and recording any accessory nerve movements. The self-retaining sternal retractors were fully opened to a mean inter-blade distance of 13 cm. Regardless of head position, from the initial retractor click to maximal opening there was no gross movement of the accessory nerve on the left or right sides. Opening self-retaining sternal retractors does not appear to stretch the accessory nerve in the posterior cervical triangle. Based on our clinical experience and cadaveric results, we believe that inflammatory conditions, (i.e., idiopathic brachial plexitis) can involve the accessory nerve, and might be triggered by surgical procedures. Clin. Anat. 31:417-421, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. 21 CFR 884.2660 - Fetal ultrasonic monitor and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal ultrasonic monitor and accessories. 884.2660... Devices § 884.2660 Fetal ultrasonic monitor and accessories. (a) Identification. A fetal ultrasonic monitor is a device designed to transmit and receive ultrasonic energy into and from the pregnant woman...

  13. Regulation of protein turnover by heat shock proteins.

    PubMed

    Bozaykut, Perinur; Ozer, Nesrin Kartal; Karademir, Betul

    2014-12-01

    Protein turnover reflects the balance between synthesis and degradation of proteins, and it is a crucial process for the maintenance of the cellular protein pool. The folding of proteins, refolding of misfolded proteins, and also degradation of misfolded and damaged proteins are involved in the protein quality control (PQC) system. Correct protein folding and degradation are controlled by many different factors, one of the most important of which is the heat shock protein family. Heat shock proteins (HSPs) are in the class of molecular chaperones, which may prevent the inappropriate interaction of proteins and induce correct folding. On the other hand, these proteins play significant roles in the degradation pathways, including endoplasmic reticulum-associated degradation (ERAD), the ubiquitin-proteasome system, and autophagy. This review focuses on the emerging role of HSPs in the regulation of protein turnover; the effects of HSPs on the degradation machineries ERAD, autophagy, and proteasome; as well as the role of posttranslational modifications in the PQC system. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Role of N-terminal domain and accessory subunits in controlling deactivation-inactivation coupling of Kv4.2 channels.

    PubMed

    Barghaan, Jan; Tozakidou, Magdalini; Ehmke, Heimo; Bähring, Robert

    2008-02-15

    We examined the relationship between deactivation and inactivation in Kv4.2 channels. In particular, we were interested in the role of a Kv4.2 N-terminal domain and accessory subunits in controlling macroscopic gating kinetics and asked if the effects of N-terminal deletion and accessory subunit coexpression conform to a kinetic coupling of deactivation and inactivation. We expressed Kv4.2 wild-type channels and N-terminal deletion mutants in the absence and presence of Kv channel interacting proteins (KChIPs) and dipeptidyl aminopeptidase-like proteins (DPPs) in human embryonic kidney 293 cells. Kv4.2-mediated A-type currents at positive and deactivation tail currents at negative membrane potentials were recorded under whole-cell voltage-clamp and analyzed by multi-exponential fitting. The observed changes in Kv4.2 macroscopic inactivation kinetics caused by N-terminal deletion, accessory subunit coexpression, or a combination of the two maneuvers were compared with respective changes in deactivation kinetics. Extensive correlation analyses indicated that modulatory effects on deactivation closely parallel respective effects on inactivation, including both onset and recovery kinetics. Searching for the structural determinants, which control deactivation and inactivation, we found that in a Kv4.2 Delta 2-10 N-terminal deletion mutant both the initial rapid phase of macroscopic inactivation and tail current deactivation were slowed. On the other hand, the intermediate and slow phase of A-type current decay, recovery from inactivation, and tail current decay kinetics were accelerated in Kv4.2 Delta 2-10 by KChIP2 and DPPX. Thus, a Kv4.2 N-terminal domain, which may control both inactivation and deactivation, is not necessary for active modulation of current kinetics by accessory subunits. Our results further suggest distinct mechanisms for Kv4.2 gating modulation by KChIPs and DPPs.

  15. Iron oxide nanoparticles modulate heat shock proteins and organ specific markers expression in mice male accessory organs.

    PubMed

    Sundarraj, Kiruthika; Raghunath, Azhwar; Panneerselvam, Lakshmikanthan; Perumal, Ekambaram

    2017-02-15

    With increased industrial utilization of iron oxide nanoparticles (Fe 2 O 3 -NPs), concerns on adverse reproductive health effects following exposure have been immensely raised. In the present study, the effects of Fe 2 O 3 -NPs exposure in the seminal vesicle and prostate gland were studied in mice. Mice were exposed to two different doses (25 and 50 mg/kg) of Fe 2 O 3 -NPs along with the control and analyzed the expressions of heat shock proteins (HSP60, HSP70 and HSP90) and organ specific markers (Caltrin, PSP94, and SSLP1). Fe 2 O 3 -NPs decreased food consumption, water intake, and organo-somatic index in mice with elevated iron levels in serum, urine, fecal matter, seminal vesicle and prostate gland. FTIR spectra revealed alterations in the functional groups of biomolecules on Fe 2 O 3 -NPs treatment. These changes are accompanied by increased lactate dehydrogenase levels with decreased total protein and fructose levels. The investigation of oxidative stress biomarkers demonstrated a significant increase in reactive oxygen species, nitric oxide, lipid peroxidation, protein carbonyl content and glutathione peroxidase with a concomitant decrement in the glutathione and ascorbic acid in the male accessory organs which confirmed the induction of oxidative stress. An increase in NADPH-oxidase-4 with a decrease in glutathione-S-transferase was observed in the seminal vesicle and prostate gland of the treated groups. An alteration in HSP60, HSP70, HSP90, Caltrin, PSP94, and SSLP1 expression was also observed. Moreover, accumulation of Fe 2 O 3 -NPs brought pathological changes in the seminal vesicle and prostate gland of treated mice. These findings provide evidence that Fe 2 O 3 -NPs could be an environmental risk factor for reproductive disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Cardiotonic Steroids Stabilize Regulator of G Protein Signaling 2 Protein Levels

    PubMed Central

    Sjögren, Benita; Parra, Sergio; Heath, Lauren J.; Atkins, Kevin B.; Xie, Zie-Jian

    2012-01-01

    Regulator of G protein signaling 2 (RGS2), a Gq-specific GTPase-activating protein, is strongly implicated in cardiovascular function. RGS2(−/−) mice are hypertensive and prone to heart failure, and several rare human mutations that accelerate RGS2 degradation have been identified among patients with hypertension. Therefore, pharmacological up-regulation of RGS2 protein levels might be beneficial. We used a β-galactosidase complementation method to screen several thousand compounds with known pharmacological functions for those that increased RGS2 protein levels. Several cardiotonic steroids (CTSs), including ouabain and digoxin, increased RGS2 but not RGS4 protein levels. CTSs increased RGS2 protein levels through a post-transcriptional mechanism, by slowing protein degradation. RGS2 mRNA levels in primary vascular smooth muscle cells were unaffected by CTS treatment, whereas protein levels were increased 2- to 3-fold. Na+/K+-ATPase was required for the increase in RGS2 protein levels, because the effect was lost in Na+/K+-ATPase-knockdown cells. Furthermore, we demonstrated that CTS-induced increases in RGS2 levels were functional and reduced receptor-stimulated, Gq-dependent, extracellular signal-regulated kinase phosphorylation. Finally, we showed that in vivo treatment with digoxin led to increased RGS2 protein levels in heart and kidney. CTS-induced increases in RGS2 protein levels and function might modify several deleterious mechanisms in hypertension and heart failure. This novel CTS mechanism might contribute to the beneficial actions of low-dose digoxin treatment in heart failure. Our results support the concept of small-molecule modulation of RGS2 protein levels as a new strategy for cardiovascular therapy. PMID:22695717

  17. Regulation of PXR and CAR by protein-protein interaction and signaling crosstalk

    PubMed Central

    Oladimeji, Peter; Cui, Hongmei; Zhang, Chen; Chen, Taosheng

    2016-01-01

    Introduction Protein-protein interaction and signaling crosstalk contribute to the regulation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) and broaden their cellular function. Area covered This review covers key historic discoveries and recent advances in our understanding of the broad function of PXR and CAR and their regulation by protein-protein interaction and signaling crosstalk. Expert opinion PXR and CAR were first discovered as xenobiotic receptors. However, it is clear that PXR and CAR perform a much broader range of cellular functions through protein-protein interaction and signaling crosstalk, which typically mutually affect the function of all the partners involved. Future research on PXR and CAR should, therefore, look beyond their xenobiotic function. PMID:27295009

  18. Role of Regulators of G Protein Signaling Proteins in Bone Physiology and Pathophysiology.

    PubMed

    Jules, Joel; Yang, Shuying; Chen, Wei; Li, Yi-Ping

    2015-01-01

    Regulators of G protein signaling (RGS) proteins enhance the intrinsic GTPase activity of α subunits of the heterotrimeric G protein complex of G protein-coupled receptors (GPCRs) and thereby inactivate signal transduction initiated by GPCRs. The RGS family consists of nearly 37 members with a conserved RGS homology domain which is critical for their GTPase accelerating activity. RGS proteins are expressed in most tissues, including heart, lung, brain, kidney, and bone and play essential roles in many physiological and pathological processes. In skeletal development and bone homeostasis as well as in many bone disorders, RGS proteins control the functions of various GPCRs, including the parathyroid hormone receptor type 1 and calcium-sensing receptor and also regulate various critical signaling pathways, such as Wnt and calcium oscillations. This chapter will discuss the current findings on the roles of RGS proteins in regulating signaling of key GPCRs in skeletal development and bone homeostasis. We also will examine the current updates of RGS proteins' regulation of calcium oscillations in bone physiology and highlight the roles of RGS proteins in selected bone pathological disorders. Despite the recent advances in bone and mineral research, RGS proteins remain understudied in the skeletal system. Further understanding of the roles of RGS proteins in bone should not only provide great insights into the molecular basis of various bone diseases but also generate great therapeutic drug targets for many bone diseases. © 2015 Elsevier Inc. All rights reserved.

  19. Accessory wandering spleen: Report of a case of laparoscopic approach in an asymptomatic patient

    PubMed Central

    Perin, Alessandro; Cola, Roberto; Favretti, Franco

    2014-01-01

    INTRODUCTION Accessory wandering spleen is a rare but dangerous condition. Abnormalities of the ligamentous apparatus of an accessory spleen may evolve into torsion of its vascular axis, which can lead to a splenic infarct making surgery necessary. Patients are often asymptomatic and the diagnosis can be accidental. An early diagnosis and a correct treatment are fundamental. PRESENTATION OF CASE In this case report a young woman underwent laparoscopic surgery after an incidental finding at a Pelvic Ultrasound of an accessory wandering spleen. DISCUSSION In literature are reported cases of asymptomatic patients with an accessory wandering spleen treated with a conservative approach. However, a torsion or infarct of the accessory wandering spleen leads to emergency surgery. The presence of an independent vascular axis of the accessory spleen reduces the risk of postoperative complications (e.g. thrombocytosis) and the administration of low molecular weight heparin should prevent the risk of portal thrombosis. CONCLUSION We suggest performing surgery with a laparoscopic approach in patients with accessory wandering spleen, though asymptomatic, because of the risk of serious complications in case of accessory spleen torsion. PMID:25460427

  20. Accessory breasts: a historical and current perspective.

    PubMed

    Loukas, Marios; Clarke, Pamela; Tubbs, R Shane

    2007-05-01

    The presence of accessory breast tissue such as extra nipples (polythelia) and extra breast (polymastia) is relatively common, with a high incidence of being misdiagnosed in clinical medicine. Although polythelia is congenital in origin and is identifiable at childhood, polymastia may not be evident until the influence of sex hormones during puberty. In this article, we present a review of the literature concerning the historical background of accessory breasts, their incidence, their misdiagnoses, and their association with other syndromes and diseases. Finally, we present the common treatment options available today for such conditions.

  1. The benefits of using bluetooth accessories with hearing aids.

    PubMed

    Smith, Pauline; Davis, Adrian

    2014-10-01

    To investigate the benefits in reported outcomes after providing bluetooth accessories for established hearing aid users. Prospective observational study using validated quantitative outcome measures and detailed patient narrative before and two months after patients were provided with bluetooth accessories. Twelve patients with bilateral NHS hearing aids participated. They had a wide range of ages and hearing loss. After two months, 10 patients reported substantial additional benefit and kept the accessories; two returned them for various reasons. Statistically significant changes were seen in two validated outcome measures: the Glasgow Hearing Aid Benefit Profile and the International Outcome Inventory - Hearing Aids, but not in the Speech, Spatial and Qualities of Hearing Scale. Two notable benefits were reported: some described hearing the emotion and mood in a voice for the first time; others were amazed to report an improved ability to hear film or to hold conversations over the telephone. The provision of bluetooth accessories can give additional reported benefit for some patients - we need better knowledge about who benefits, and whether further support/training to individuals would make a difference.

  2. Crystallization of accessory phases in magmas by local saturation adjacent to phenocrysts

    USGS Publications Warehouse

    Bacon, C.R.

    1989-01-01

    Accessory minerals commonly occur attached to or included in the major crystalline phases of felsic and some intermediate igneous rocks. Apatite is particularly common as inclusions, but Fe-Ti oxides, pyrrhotite, zircon, monazite, chevkinite and xenotime are also known from silicic rocks. Accessories may nucleate near the host crystal/ liquid interface as a result of local saturation owing to formation of a differentiated chemical boundary layer in which accessory mineral solubility would be lower than in the surrounding liquid. Differentiation of this boundary layer would be greatest adjacent to ferromagnesian phenocrysts, especially Fe-Ti oxides; it is with oxides that accessories are most commonly associated in rocks. A boundary layer may develop if the crystal grows more rapidly than diffusion can transport incorporated and rejected elements to and from the phenocryst. Diffusion must dominate over convection as a mode of mass transfer near the advancing crystal/liquid interface in order for a boundary layer to exist. Accumulation of essential structural constituent elements of accessory minerals owing to their slow diffusion in evolved silicate melt also may force local saturation, but this is not a process that applies to all cases. Local saturation is an attractive mechanism for enhancing fractionation during crystallization differentiation. If accessory minerals attached to or included in phenocrysts formed because of local saturation, their host phenocrysts must have grown rapidly when accessories nucleated in comparison to lifetimes of magma reservoirs. Some inconsistencies remain in a local saturation origin for accessory phases that cannot be evaluated without additional information. ?? 1989.

  3. Differential regulation of oligodendrocyte markers by glucocorticoids: Post-transcriptional regulation of both proteolipid protein and myelin basic protein and transcriptional regulation of glycerol phosphate dehydrogenase

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

    Kumar, S.; Cole, R.; Chiappelli, F.

    During neonatal development glucocorticoids potentiate oligodendrocyte differentiation and myelinogenesis by regulating the expression of myelin basic protein, proteolipid protein, and glycerol phosphate dehydrogenase. The actual locus at which hydrocortisone exerts its developmental influence on glial physiology is, however, not well understood. Gycerol phosphate dehydrogenase is glucocorticoid-inducible in oligodendrocytes at all stages of development both in vivo and in vitro. In newborn rat cerebral cultures, between 9 and 15 days in vitro, a 2- to 3-fold increase in myelin basic protein and proteolipid protein mRNA levels occurs in oligodendrocytes within 12 hr of hydrocortisone treatment. Immunostaining demonstrates that this increase inmore » mRNAs is followed by a 2- to 3-fold increase in the protein levels within 24 hr. In vitro transcription assays performed with oligodendrocyte nuclei show an 11-fold increase in the transcriptional activity of glycerol phosphate dehydrogenase in response to hydrocortisone but no increase in transcription of myelin basic protein or proteolipid protein. These results indicate that during early myelinogeneis, glucocorticoids influence the expression of key oligodendroglial markers by different processes: The expression of glycerol phosphate dehydrogenase is regulated at the transcriptional level, whereas the expression of myelin basic protein and proteolipid protein is modulated via a different, yet uncharacterized, mechanism involving post-transcriptional regulation.« less

  4. Regulation of intestinal protein metabolism by amino acids.

    PubMed

    Bertrand, Julien; Goichon, Alexis; Déchelotte, Pierre; Coëffier, Moïse

    2013-09-01

    Gut homeostasis plays a major role in health and may be regulated by quantitative and qualitative food intake. In the intestinal mucosa, an intense renewal of proteins occurs, at approximately 50% per day in humans. In some pathophysiological conditions, protein turnover is altered and may contribute to intestinal or systemic diseases. Amino acids are key effectors of gut protein turnover, both as constituents of proteins and as regulatory molecules limiting intestinal injury and maintaining intestinal functions. Many studies have focused on two amino acids: glutamine, known as the preferential substrate of rapidly dividing cells, and arginine, another conditionally essential amino acid. The effects of glutamine and arginine on protein synthesis appear to be model and condition dependent, as are the involved signaling pathways. The regulation of gut protein degradation by amino acids has been minimally documented until now. This review will examine recent data, helping to better understand how amino acids regulate intestinal protein metabolism, and will explore perspectives for future studies.

  5. Regulation of SMN Protein Stability▿ †

    PubMed Central

    Burnett, Barrington G.; Muñoz, Eric; Tandon, Animesh; Kwon, Deborah Y.; Sumner, Charlotte J.; Fischbeck, Kenneth H.

    2009-01-01

    Spinal muscular atrophy (SMA) is caused by mutations of the survival of motor neuron (SMN1) gene and deficiency of full-length SMN protein (FL-SMN). All SMA patients retain one or more copies of the SMN2 gene, but the principal protein product of SMN2 lacks exon 7 (SMNΔ7) and is unable to compensate for a deficiency of FL-SMN. SMN is known to oligomerize and form a multimeric protein complex; however, the mechanisms regulating stability and degradation of FL-SMN and SMNΔ7 proteins have been largely unexplored. Using pulse-chase analysis, we characterized SMN protein turnover and confirmed that SMN was ubiquitinated and degraded by the ubiquitin proteasome system (UPS). The SMNΔ7 protein had a twofold shorter half-life than FL-SMN in cells despite similar intrinsic rates of turnover by the UPS in a cell-free assay. Mutations that inhibited SMN oligomerization and complex formation reduced the FL-SMN half-life. Furthermore, recruitment of SMN into large macromolecular complexes as well as increased association with several Gemin proteins was regulated in part by protein kinase A. Together, our data indicate that SMN protein stability is modulated by complex formation. Promotion of the SMN complex formation may be an important novel therapeutic strategy for SMA. PMID:19103745

  6. Role of Regulators of G Protein Signaling Proteins in Bone Physiology and Pathophysiology

    PubMed Central

    Jules, Joel; Yang, Shuying; Chen, Wei; Li, Yi-Ping

    2016-01-01

    Regulators of G protein signaling (RGS) proteins enhance the intrinsic GTPase activity of α subunits of the heterotrimeric G protein complex of G protein-coupled receptors (GPCRs) and thereby inactivate signal transduction initiated by GPCRs. The RGS family consists of nearly 37 members with a conserved RGS homology domain which is critical for their GTPase accelerating activity. RGS proteins are expressed in most tissues, including heart, lung, brain, kidney, and bone and play essential roles in many physiological and pathological processes. In skeletal development and bone homeostasis as well as in many bone disorders, RGS proteins control the functions of various GPCRs, including the parathyroid hormone receptor type 1 and calcium-sensing receptor and also regulate various critical signaling pathways, such as Wnt and calcium oscillations. This chapter will discuss the current findings on the roles of RGS proteins in regulating signaling of key GPCRs in skeletal development and bone homeostasis. We also will examine the current updates of RGS proteins’ regulation of calcium oscillations in bone physiology and highlight the roles of RGS proteins in selected bone pathological disorders. Despite the recent advances in bone and mineral research, RGS proteins remain understudied in the skeletal system. Further understanding of the roles of RGS proteins in bone should not only provide great insights into the molecular basis of various bone diseases but also generate great therapeutic drug targets for many bone diseases. PMID:26123302

  7. 26 CFR 48.4061(b)-3 - Rebuilt, reconditioned, or repaired parts or accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., reconditioned, or repaired parts or accessories. (a) Rebuilt parts or accessories. Rebuilding of automobile... for the person reassembling the generator, (6) reground or remetalized crankshafts, and (7) engines in... reassembling (with any necessary replacements of worn parts) of automobile parts or accessories, such as fuel...

  8. 26 CFR 48.4061(b)-3 - Rebuilt, reconditioned, or repaired parts or accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., reconditioned, or repaired parts or accessories. (a) Rebuilt parts or accessories. Rebuilding of automobile... for the person reassembling the generator, (6) reground or remetalized crankshafts, and (7) engines in... reassembling (with any necessary replacements of worn parts) of automobile parts or accessories, such as fuel...

  9. 26 CFR 48.4061(b)-3 - Rebuilt, reconditioned, or repaired parts or accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., reconditioned, or repaired parts or accessories. (a) Rebuilt parts or accessories. Rebuilding of automobile... for the person reassembling the generator, (6) reground or remetalized crankshafts, and (7) engines in... reassembling (with any necessary replacements of worn parts) of automobile parts or accessories, such as fuel...

  10. HnRNP-like proteins as post-transcriptional regulators.

    PubMed

    Yeap, Wan-Chin; Namasivayam, Parameswari; Ho, Chai-Ling

    2014-10-01

    Plant cells contain a diverse repertoire of RNA-binding proteins (RBPs) that coordinate a network of post-transcriptional regulation. RBPs govern diverse developmental processes by modulating the gene expression of specific transcripts. Recent gene annotation and RNA sequencing clearly showed that heterogeneous nuclear ribonucleoprotein (hnRNP)-like proteins which form a family of RBPs, are also expressed in higher plants and serve specific plant functions. In addition to their involvement in post-transcriptional regulation from mRNA capping to translation, they are also involved in telomere regulation, gene silencing and regulation in chloroplast. Here, we review the involvement of plant hnRNP-like proteins in post-transcription regulation of RNA processes and their functional roles in control of plant developmental processes especially plant-specific functions including flowering, chloroplastic-specific mRNA regulation, long-distance phloem transportation and plant responses to environmental stresses. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Two Chimeric Regulators of G-protein Signaling (RGS) Proteins Differentially Modulate Soybean Heterotrimeric G-protein Cycle*

    PubMed Central

    Roy Choudhury, Swarup; Westfall, Corey S.; Laborde, John P.; Bisht, Naveen C.; Jez, Joseph M.; Pandey, Sona

    2012-01-01

    Heterotrimeric G-proteins and the regulator of G-protein signaling (RGS) proteins, which accelerate the inherent GTPase activity of Gα proteins, are common in animals and encoded by large gene families; however, in plants G-protein signaling is thought to be more limited in scope. For example, Arabidopsis thaliana contains one Gα, one Gβ, three Gγ, and one RGS protein. Recent examination of the Glycine max (soybean) genome reveals a larger set of G-protein-related genes and raises the possibility of more intricate G-protein networks than previously observed in plants. Stopped-flow analysis of GTP-binding and GDP/GTP exchange for the four soybean Gα proteins (GmGα1–4) reveals differences in their kinetic properties. The soybean genome encodes two chimeric RGS proteins with an N-terminal seven transmembrane domain and a C-terminal RGS box. Both GmRGS interact with each of the four GmGα and regulate their GTPase activity. The GTPase-accelerating activities of GmRGS1 and -2 differ for each GmGα, suggesting more than one possible rate of the G-protein cycle initiated by each of the Gα proteins. The differential effects of GmRGS1 and GmRGS2 on GmGα1–4 result from a single valine versus alanine difference. The emerging picture suggests complex regulation of the G-protein cycle in soybean and in other plants with expanded G-protein networks. PMID:22474294

  12. 14 CFR 221.52 - Airport to airport application, accessorial services.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Airport to airport application, accessorial... Charges § 221.52 Airport to airport application, accessorial services. Tariffs shall specify whether or not the fares therein include services in addition to airport-to-airport transportation. ...

  13. 14 CFR 221.52 - Airport to airport application, accessorial services.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Airport to airport application, accessorial... Charges § 221.52 Airport to airport application, accessorial services. Tariffs shall specify whether or not the fares therein include services in addition to airport-to-airport transportation. ...

  14. 14 CFR 221.52 - Airport to airport application, accessorial services.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Airport to airport application, accessorial... Charges § 221.52 Airport to airport application, accessorial services. Tariffs shall specify whether or not the fares therein include services in addition to airport-to-airport transportation. ...

  15. 14 CFR 221.52 - Airport to airport application, accessorial services.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Airport to airport application, accessorial... Charges § 221.52 Airport to airport application, accessorial services. Tariffs shall specify whether or not the fares therein include services in addition to airport-to-airport transportation. ...

  16. 14 CFR 221.52 - Airport to airport application, accessorial services.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Airport to airport application, accessorial... Charges § 221.52 Airport to airport application, accessorial services. Tariffs shall specify whether or not the fares therein include services in addition to airport-to-airport transportation. ...

  17. Accessory mineral records of tectonic environments? (Invited)

    NASA Astrophysics Data System (ADS)

    Storey, C.; Marschall, H. R.; Enea, F.; Taylor, J.; Jennings, E. S.

    2010-12-01

    Accessory mineral research continues to gather momentum as we seek to unleash their full potential. It is now widely recognised that robust accessory minerals, such as zircon, rutile, titanite, allanite and monazite, are archives of important trace elements that can help deduce metamorphic reaction history in metapelites, metabasites and other rock types. Moreover, they are important carriers of certain trace elements and govern or influence the products of partial melting and of fluid-rock interaction (e.g. magmas and mineralisation) in settings like subduction zones and hydrothermal systems. Perhaps most importantly, they can often be dated using the U-Th-Pb system. More recently, radiogenic (Lu-Hf, Sm-Nd, Rb-Sr) and stable (O) isotope systems have been applied and have further pushed the utility of accessory mineral research. In this talk I will discuss some of these advances towards one particular aim: the use of detrital accessory minerals for fingerprinting tectonic environments. This is a particularly laudable aim in Precambrian rocks, for which the preservation potential of orogenic belts and fossil subduction zones and their diagnostic metamorphic rocks is low. The implication is that our understanding of plate tectonics, particularly in the Archaean, is biased by the preserved in-tact rock record. An analogy is that Jack Hills zircons record evidence of Earth’s crust some 400 Ma before the preserved rock record begins. I will focus on some recent advances and new data from rutile and also the mineral inclusion record within zircon, which shows great promise for petrologic interpretation.

  18. Accessory Devices Frequently Used for Endoscopic Submucosal Dissection

    PubMed Central

    Choi, Hyuk Soon; Chun, Hoon Jai

    2017-01-01

    Endoscopic submucosal dissection (ESD) is increasingly being considered an essential component of treatment for early gastrointestinal cancers and subepithelial tumors. The ESD technique owes its popularity to the development of sophisticated instruments used for ESD. With an increase in the number of ESD procedures performed, there is rapid development in the number and types of endoscopic accessory devices used for such procedures. Despite the large numbers of new devices developed and marketed, the use of ESD instruments and accessory devices is largely determined by individual preferences and experiences. Accessory devices frequently used during ESD are important tools for ESD techniques. Each instrument possesses characteristic advantages and disadvantages associated with its use, and no one instrument is superior in all respects to others. In this article, we review the characteristics of endoscopic electrical knives, cap and hood, and hemostatic devices commonly used in ESD. PMID:28609818

  19. 21 CFR 884.1300 - Uterotubal carbon dioxide insufflator and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Uterotubal carbon dioxide insufflator and... Gynecological Diagnostic Devices § 884.1300 Uterotubal carbon dioxide insufflator and accessories. (a) Identification. A uterotubal carbon dioxide insufflator and accessories is a device used to test the patency...

  20. 21 CFR 884.1300 - Uterotubal carbon dioxide insufflator and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Uterotubal carbon dioxide insufflator and... Gynecological Diagnostic Devices § 884.1300 Uterotubal carbon dioxide insufflator and accessories. (a) Identification. A uterotubal carbon dioxide insufflator and accessories is a device used to test the patency...

  1. 21 CFR 884.1300 - Uterotubal carbon dioxide insufflator and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Uterotubal carbon dioxide insufflator and... Gynecological Diagnostic Devices § 884.1300 Uterotubal carbon dioxide insufflator and accessories. (a) Identification. A uterotubal carbon dioxide insufflator and accessories is a device used to test the patency...

  2. 21 CFR 888.5850 - Nonpowered orthopedic traction apparatus and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nonpowered orthopedic traction apparatus and accessories. 888.5850 Section 888.5850 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... orthopedic traction apparatus and accessories. (a) Identification. A nonpowered orthopedic traction apparatus...

  3. 21 CFR 888.5850 - Nonpowered orthopedic traction apparatus and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nonpowered orthopedic traction apparatus and accessories. 888.5850 Section 888.5850 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... orthopedic traction apparatus and accessories. (a) Identification. A nonpowered orthopedic traction apparatus...

  4. A conserved NAD+ binding pocket that regulates protein-protein interactions during aging

    PubMed Central

    Li, Jun; Bonkowski, Michael S.; Moniot, Sébastien; Zhang, Dapeng; Hubbard, Basil P.; Ling, Alvin J. Y.; Rajman, Luis A.; Qin, Bo; Lou, Zhenkun; Gorbunova, Vera; Aravind, L.; Steegborn, Clemens; Sinclair, David A.

    2017-01-01

    DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD+ (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD+ to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine diphosphate–ribose) polymerase], a critical DNA repair protein. As mice age and NAD+ concentrations decline, DBC1 is increasingly bound to PARP1, causing DNA damage to accumulate, a process rapidly reversed by restoring the abundance of NAD+. Thus, NAD+ directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging. PMID:28336669

  5. [Fibroadenoma in an accessory breast. A case of polythelia and fibroadenoma in the left breast region and a perivulvar accessory breast].

    PubMed

    Degrell, I

    1979-08-02

    The case of a 32-year-old female patient with multiple malformations (hare-lip, polythelia, fibroadenoma in an accessory mammary gland) and independent of these, another fibroadenoma in the breast is reported. The fibroadenoma developing in the accessory breast around the vulva, diagnosed by means of aspiration biopsy cytology, should be payed special attention. This case also confirms the applicability in preoperative diagnostics of aspiration biopsy cytology, a method which has proved to be effective for years.

  6. Fluorescence-based assay probing regulator of G protein signaling partner proteins.

    PubMed

    Huang, Po-Shiun; Yeh, Hsin-Sung; Yi, Hsiu-Ping; Lin, Chain-Jia; Yang, Chii-Shen

    2012-04-01

    The regulator of G protein signaling (RGS) proteins are one of the essential modulators for the G protein system. Besides regulating G protein signaling by accelerating the GTPase activity of Gα subunits, RGS proteins are implicated in exerting other functions; they are also known to be involved in several diseases. Moreover, the existence of a single RGS protein in plants and its seven-transmembrane domain found in 2003 triggered efforts to unveil detailed structural and functional information of RGS proteins. We present a method for real-time examination of the protein-protein interactions between RGS and Gα subunits. AtRGS1 from plants and RGS4 from mammals were site-directedly labeled with the fluorescent probe Lucifer yellow on engineered cysteine residues and used to interact with different Gα subunits. The physical interactions can be revealed by monitoring the real-time fluorescence changes (8.6% fluorescence increase in mammals and 27.6% in plants); their correlations to functional exertion were shown with a GTPase accelerating activity assay and further confirmed by measurement of K(d). We validate the effectiveness of this method and suggest its application to the exploration of more RGS signaling partner proteins in physiological and pathological studies. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Accessory costs of seed production and the evolution of angiosperms.

    PubMed

    Lord, Janice M; Westoby, Mark

    2012-01-01

    Accessory costs of reproduction frequently equal or exceed direct investment in offspring, and can limit the evolution of small offspring sizes. Early angiosperms had minimum seed sizes, an order of magnitude smaller than their contemporaries. It has been proposed that changes to reproductive features at the base of the angiosperm clade reduced accessory costs thus removing the fitness disadvantage of small seeds. We measured accessory costs of reproduction in 25 extant gymnosperms and angiosperms, to test whether angiosperms can produce small seeds more economically than gymnosperms. Total accessory costs scaled isometrically to seed mass for angiosperms but less than isometrically for gymnosperms, so that smaller seeds were proportionally more expensive for gymnosperms to produce. In particular, costs of abortions and packaging structures were significantly higher in gymnosperms. Also, the relationship between seed:ovule ratio and seed size was negative in angiosperms but positive in gymnosperms. We argue that the carpel was a key evolutionary innovation reducing accessory costs in angiosperms by allowing sporophytic control of pre- and postzygotic mate selection and timing of resource allocation. The resulting reduction in costs of aborting unfertilized ovules or genetically inferior embryos would have lowered total reproductive costs enabling early angiosperms to evolve small seed sizes and short generation times. © 2011 The Author(s). Evolution © 2011 The Society for the Study of Evolution.

  8. [Evaluation of iatrogenic accessory nerve injury in forensic medical practice].

    PubMed

    Somogyi, E; Irányi, J

    1996-04-14

    The authors give a survey of the clinical and medical-legal characteristics of the accessory nerve injury. In the past two decades the conception of the successfulness of the surgical treatment of the accessory nerve injury became prevailing. About the medical-legal aspects of the iatrogenic injury of the nerve reported in connection of the reconstructive surgery chiefly also departments of neurosurgery, orthopedics and traumatology. In the case of the authors a 70 year old patient suffered 10 years ago a iatrogenic accessory nerve injury. The mild trapezius palsy recovered spontaneously practically with cosmetic disadvantage. In connection with the development of extreme dorso-lumbal scoliosis associated with torsion the trapezius atrophy worsened. Physical therapy was partly successful. But the patient became unfit for manual work. Their observations sustain the data of authors who established that in the case of accessory nerve injury not only the surgical but also conservative treatment is usually successful. In opposite to certain data of the literature the authors establish that the iatrogenic injuries of the accessory nerve may lead to significant lifelong disability. The diagnosis is not always made in time with consequent delay in repair. This may be regarded as an unfavorable issue during medical-legal discussions. The authors recommend in interest to prevent nerve injury in the posterior triangle of the neck to perform operation in special department.

  9. PDZ Protein Regulation of G Protein-Coupled Receptor Trafficking and Signaling Pathways.

    PubMed

    Dunn, Henry A; Ferguson, Stephen S G

    2015-10-01

    G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases. As a consequence, understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacological strategies for the treatment of human pathologies. Of the many GPCR-interacting proteins, postsynaptic density protein of 95 kilodaltons, disc large, zona occludens-1 (PDZ) domain-containing proteins appear most abundant and have similarly been implicated in disease mechanisms. PDZ proteins play an important role in regulating receptor and channel protein localization within synapses and tight junctions and function to scaffold intracellular signaling protein complexes. In the current study, we review the known functional interactions between PDZ domain-containing proteins and GPCRs and provide insight into the potential mechanisms of action. These PDZ domain-containing proteins include the membrane-associated guanylate-like kinases [postsynaptic density protein of 95 kilodaltons; synapse-associated protein of 97 kilodaltons; postsynaptic density protein of 93 kilodaltons; synapse-associated protein of 102 kilodaltons; discs, large homolog 5; caspase activation and recruitment domain and membrane-associated guanylate-like kinase domain-containing protein 3; membrane protein, palmitoylated 3; calcium/calmodulin-dependent serine protein kinase; membrane-associated guanylate kinase protein (MAGI)-1, MAGI-2, and MAGI-3], Na(+)/H(+) exchanger regulatory factor proteins (NHERFs) (NHERF1, NHERF2, PDZ domain-containing kidney protein 1, and PDZ domain-containing kidney protein 2), Golgi-associated PDZ proteins (Gα-binding protein interacting protein, C-terminus and CFTR-associated ligand), PDZ domain-containing guanine nucleotide exchange factors (GEFs) 1 and 2, regulator of G protein signaling (RGS)-homology-RhoGEFs (PDZ domain-containing RhoGEF and

  10. A conserved NAD+ binding pocket that regulates protein-protein interactions during aging.

    PubMed

    Li, Jun; Bonkowski, Michael S; Moniot, Sébastien; Zhang, Dapeng; Hubbard, Basil P; Ling, Alvin J Y; Rajman, Luis A; Qin, Bo; Lou, Zhenkun; Gorbunova, Vera; Aravind, L; Steegborn, Clemens; Sinclair, David A

    2017-03-24

    DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD + (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD + to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine diphosphate-ribose) polymerase], a critical DNA repair protein. As mice age and NAD + concentrations decline, DBC1 is increasingly bound to PARP1, causing DNA damage to accumulate, a process rapidly reversed by restoring the abundance of NAD + Thus, NAD + directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging. Copyright © 2017, American Association for the Advancement of Science.

  11. Regulation of alternative splicing in Drosophila by 56 RNA binding proteins

    DOE PAGES

    Brooks, Angela N.; Duff, Michael O.; May, Gemma; ...

    2015-08-20

    Alternative splicing is regulated by RNA binding proteins (RBPs) that recognize pre-mRNA sequence elements and activate or repress adjacent exons. Here, we used RNA interference and RNA-seq to identify splicing events regulated by 56 Drosophila proteins, some previously unknown to regulate splicing. Nearly all proteins affected alternative first exons, suggesting that RBPs play important roles in first exon choice. Half of the splicing events were regulated by multiple proteins, demonstrating extensive combinatorial regulation. We observed that SR and hnRNP proteins tend to act coordinately with each other, not antagonistically. We also identified a cross-regulatory network where splicing regulators affected themore » splicing of pre-mRNAs encoding other splicing regulators. In conclusion, this large-scale study substantially enhances our understanding of recent models of splicing regulation and provides a resource of thousands of exons that are regulated by 56 diverse RBPs.« less

  12. JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

    PubMed Central

    Zeke, András; Misheva, Mariya

    2016-01-01

    SUMMARY The c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states. PMID:27466283

  13. JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships.

    PubMed

    Zeke, András; Misheva, Mariya; Reményi, Attila; Bogoyevitch, Marie A

    2016-09-01

    The c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Plasma levels of soluble interleukin 1 receptor accessory protein are reduced in obesity.

    PubMed

    Bozaoglu, Kiymet; Attard, Chantal; Kulkarni, Hemant; Cummings, Nik; Diego, Vincent P; Carless, Melanie A; Shields, Katherine A; Johnson, Matthew P; Kowlessur, Sudhir; Dyer, Thomas D; Comuzzie, Anthony G; Almasy, Laura; Zimmet, Paul; Moses, Eric K; Göring, Harald H H; Curran, Joanne E; Blangero, John; Jowett, Jeremy B M

    2014-09-01

    Adipokines actuate chronic, low-grade inflammation through a complex network of immune markers, but the current understanding of these networks is incomplete. The soluble isoform of the IL-1 receptor accessory protein (sIL1RAP) occupies an important position in the inflammatory pathways involved in obesity. The pathogenetic and clinical influences of sIL1RAP are unknown. The objective of the study was to elucidate whether plasma levels of sIL1RAP are reduced in obesity, using affluent clinical, biochemical, and genetic data from two diverse cohorts. The study was conducted in two cohorts: the San Antonio Family Heart Study (n = 1397 individuals from 42 families) and South Asians living in Mauritius, n = 230). Plasma sIL1RAP levels were measured using an ELISA. The genetic basis of sIL1RAP levels were investigated using both a large-scale gene expression profiling study and a genome-wide association study. A significant decrease in plasma sIL1RAP levels were observed in obese subjects, even after adjustment for age and sex. The sIL1RAP levels demonstrated a strong inverse association with obesity measures in both populations. All associations were more significant in females. Plasma sIL1RAP levels were significantly heritable, correlated with IL1RAP transcript levels (NM_134470), showed evidence for shared genetic influences with obesity measures and were significantly associated with the rs2885373 single-nucleotide polymorphism (P = 6.7 × 10(-23)) within the IL1RAP gene. Plasma sIL1RAP levels are reduced in obesity and can potentially act as biomarkers of obesity. Mechanistic studies are required to understand the exact contribution of sIL1RAP to the pathogenesis of obesity.

  15. Plasma Levels of Soluble Interleukin 1 Receptor Accessory Protein Are Reduced in Obesity

    PubMed Central

    Attard, Chantal; Kulkarni, Hemant; Cummings, Nik; Diego, Vincent P.; Carless, Melanie A.; Shields, Katherine A.; Johnson, Matthew P.; Kowlessur, Sudhir; Dyer, Thomas D.; Comuzzie, Anthony G.; Almasy, Laura; Zimmet, Paul; Moses, Eric K.; Göring, Harald H. H.; Curran, Joanne E.; Blangero, John; Jowett, Jeremy B. M.

    2014-01-01

    Context: Adipokines actuate chronic, low-grade inflammation through a complex network of immune markers, but the current understanding of these networks is incomplete. The soluble isoform of the IL-1 receptor accessory protein (sIL1RAP) occupies an important position in the inflammatory pathways involved in obesity. The pathogenetic and clinical influences of sIL1RAP are unknown. Objective: The objective of the study was to elucidate whether plasma levels of sIL1RAP are reduced in obesity, using affluent clinical, biochemical, and genetic data from two diverse cohorts. Design, Setting, and Participants: The study was conducted in two cohorts: the San Antonio Family Heart Study (n = 1397 individuals from 42 families) and South Asians living in Mauritius, n = 230). Main Outcome Measures: Plasma sIL1RAP levels were measured using an ELISA. The genetic basis of sIL1RAP levels were investigated using both a large-scale gene expression profiling study and a genome-wide association study. Results: A significant decrease in plasma sIL1RAP levels were observed in obese subjects, even after adjustment for age and sex. The sIL1RAP levels demonstrated a strong inverse association with obesity measures in both populations. All associations were more significant in females. Plasma sIL1RAP levels were significantly heritable, correlated with IL1RAP transcript levels (NM_134470), showed evidence for shared genetic influences with obesity measures and were significantly associated with the rs2885373 single-nucleotide polymorphism (P = 6.7 × 10−23) within the IL1RAP gene. Conclusions: Plasma sIL1RAP levels are reduced in obesity and can potentially act as biomarkers of obesity. Mechanistic studies are required to understand the exact contribution of sIL1RAP to the pathogenesis of obesity. PMID:24915116

  16. Simon Effect with and without Awareness of the Accessory Stimulus

    ERIC Educational Resources Information Center

    Treccani, Barbara; Umilta, Carlo; Tagliabue, Mariaelena

    2006-01-01

    The authors investigated whether a Simon effect could be observed in an accessory-stimulus Simon task when participants were unaware of the task-irrelevant accessory cue. In Experiment 1A a central visual target was accompanied by a suprathreshold visual lateral cue. A regular Simon effect (i.e., faster cue-response corresponding reaction times…

  17. Visual and auditory accessory stimulus offset and the Simon effect.

    PubMed

    Nishimura, Akio; Yokosawa, Kazuhiko

    2010-10-01

    We investigated the effect on the right and left responses of the disappearance of a task-irrelevant stimulus located on the right or left side. Participants pressed a right or left response key on the basis of the color of a centrally located visual target. Visual (Experiment 1) or auditory (Experiment 2) task-irrelevant accessory stimuli appeared or disappeared at locations to the right or left of the central target. In Experiment 1, responses were faster when onset or offset of the visual accessory stimulus was spatially congruent with the response. In Experiment 2, responses were again faster when onset of the auditory accessory stimulus and the response were on the same side. However, responses were slightly slower when offset of the auditory accessory stimulus and the response were on the same side than when they were on opposite sides. These findings indicate that transient change information is crucial for a visual Simon effect, whereas sustained stimulation from an ongoing stimulus also contributes to an auditory Simon effect.

  18. Protein Kinase A Regulates Molecular Chaperone Transcription and Protein Aggregation

    PubMed Central

    Prince, Thomas; Calderwood, Stuart K.

    2011-01-01

    Heat shock factor 1 (HSF1) regulates one of the major pathways of protein quality control and is essential for deterrence of protein-folding disorders, particularly in neuronal cells. However, HSF1 activity declines with age, a change that may open the door to progression of neurodegenerative disorders such as Huntington's disease. We have investigated mechanisms of HSF1 regulation that may become compromised with age. HSF1 binds stably to the catalytic domain of protein kinase A (PKAcα) and becomes phosphorylated on at least one regulatory serine residue (S320). We show here that PKA is essential for effective transcription of HSP genes by HSF1. PKA triggers a cascade involving HSF1 binding to the histone acetylase p300 and positive translation elongation factor 1 (p-TEFb) and phosphorylation of the c-terminal domain of RNA polymerase II, a key mechanism in the downstream steps of HSF1-mediated transcription. This cascade appears to play a key role in protein quality control in neuronal cells expressing aggregation-prone proteins with long poly-glutamine (poly-Q) tracts. Such proteins formed inclusion bodies that could be resolved by HSF1 activation during heat shock. Resolution of the inclusions was inhibited by knockdown of HSF1, PKAcα, or the pTEFb component CDK9, indicating a key role for the HSF1-PKA cascade in protein quality control. PMID:22216146

  19. Defective chemokine signal integration in leukocytes lacking activator of G protein signaling 3 (AGS3).

    PubMed

    Branham-O'Connor, Melissa; Robichaux, William G; Zhang, Xian-Kui; Cho, Hyeseon; Kehrl, John H; Lanier, Stephen M; Blumer, Joe B

    2014-04-11

    Activator of G-protein signaling 3 (AGS3, gene name G-protein signaling modulator-1, Gpsm1), an accessory protein for G-protein signaling, has functional roles in the kidney and CNS. Here we show that AGS3 is expressed in spleen, thymus, and bone marrow-derived dendritic cells, and is up-regulated upon leukocyte activation. We explored the role of AGS3 in immune cell function by characterizing chemokine receptor signaling in leukocytes from mice lacking AGS3. No obvious differences in lymphocyte subsets were observed. Interestingly, however, AGS3-null B and T lymphocytes and bone marrow-derived dendritic cells exhibited significant chemotactic defects as well as reductions in chemokine-stimulated calcium mobilization and altered ERK and Akt activation. These studies indicate a role for AGS3 in the regulation of G-protein signaling in the immune system, providing unexpected venues for the potential development of therapeutic agents that modulate immune function by targeting these regulatory mechanisms.

  20. Trafficking regulation of proteins in Alzheimer’s disease

    PubMed Central

    2014-01-01

    The β-amyloid (Aβ) peptide has been postulated to be a key determinant in the pathogenesis of Alzheimer’s disease (AD). Aβ is produced through sequential cleavage of the β-amyloid precursor protein (APP) by β- and γ-secretases. APP and relevant secretases are transmembrane proteins and traffic through the secretory pathway in a highly regulated fashion. Perturbation of their intracellular trafficking may affect dynamic interactions among these proteins, thus altering Aβ generation and accelerating disease pathogenesis. Herein, we review recent progress elucidating the regulation of intracellular trafficking of these essential protein components in AD. PMID:24410826

  1. 21 CFR 878.4400 - Electrosurgical cutting and coagulation device and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Electrosurgical cutting and coagulation device and....4400 Electrosurgical cutting and coagulation device and accessories. (a) Identification. An electrosurgical cutting and coagulation device and accessories is a device intended to remove tissue and control...

  2. Rab27a negatively regulates CFTR chloride channel function in colonic epithelia: Involvement of the effector proteins in the regulatory mechanism

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

    Saxena, Sunil K.; Kaur, Simarna

    Cystic fibrosis, an autosomal recessive disorder, is caused by the disruption of biosynthesis or function of CFTR. CFTR regulatory mechanisms include channel transport to plasma membrane and protein-protein interactions. Rab proteins are small GTPases involved in vesicle transport, docking, and fusion. The colorectal epithelial HT-29 cells natively express CFTR and respond to cAMP with an increase in CFTR-mediated currents. DPC-inhibited currents could be completely eliminated with CFTR-specific SiRNA. Over-expression of Rab27a inhibited, while isoform specific SiRNA and Rab27a antibody stimulated CFTR-mediated currents in HT-29 cells. CFTR activity is inhibited both by Rab27a (Q78L) (constitutive active GTP-bound form of Rab27a) andmore » Rab27a (T23N) (constitutive negative form that mimics the GDP-bound form). Rab27a mediated effects could be reversed by Rab27a-binding proteins, the synaptotagmin-like protein (SLP-5) and Munc13-4 accessory protein (a putative priming factor for exocytosis). The SLP reversal of Rab27a effect was restricted to C2A/C2B domains while the SHD motif imparted little more inhibition. The CFTR-mediated currents remain unaffected by Rab3 though SLP-5 appears to weakly bind it. The immunoprecipitation experiments suggest protein-protein interactions between Rab27a and CFTR. Rab27a appears to impair CFTR appearance at the cell surface by trapping CFTR in the intracellular compartments. Munc13-4 and SLP-5, on the other hand, limit Rab27a availability to CFTR, thus minimizing its effect on channel function. These observations decisively prove that Rab27a is involved in CFTR channel regulation through protein-protein interactions involving Munc13-4 and SLP-5 effector proteins, and thus could be a potential target for cystic fibrosis therapy.« less

  3. Isolation and identification of peanut leaf proteins regulated by water stress.

    PubMed

    Akkasaeng, Chutipong; Tantisuwichwong, Napaporn; Chairam, Issariya; Prakrongrak, Narumon; Jogloy, Sanun; Pathanothai, Aran

    2007-05-15

    Water deficits trigger signaling cascades leading to modulation of protein expression in plant tissues. Identification of peanut leaf proteins regulated by water stress provides some insights of cellular and molecular response of peanut plants to drought stress. Peanut variety Khon Kaen 4, a water-stress sensitive variety, was grown in a growth chamber under controlled environment. Water stress was imposed on day 30 after seedling emergence by withholding watering peanut plants for 6 days as compared to plants adequately supplied with water. Total protein were prepared from a leaflet of fully expanded leaf on the main stem. Proteins were separated in duplicated gels using two-dimensional gel electrophoresis and visualized by silver nitrate staining. Image analysis was performed using ImageMaster 2D Platinum 5.0 to determine proteins regulated by water stress. Molecular mass and isoelectric point of each regulated protein were used in database queries for protein identification. One protein was induced under water stress and the homologous protein was identified as Serine/threonine-protein phosphatase PP 1. Five proteins were down-regulated by water deficit. The homologous proteins were chaperone protein DNAJ, auxin-responsive protein IAA29, peroxidase 43, caffeoyl-CoA O-methyltransferase and SNF1-related protein kinase regulatory subunit beta-2. Down-regulated proteins may be associated with sensitivity of the peanut variety to water stress.

  4. Claudins, dietary milk proteins, and intestinal barrier regulation.

    PubMed

    Kotler, Belinda M; Kerstetter, Jane E; Insogna, Karl L

    2013-01-01

    The family of claudin proteins plays an important role in regulating the intestinal barrier by modulating the permeability of tight junctions. The impact of dietary protein on claudin biology has not been studied extensively. Whey proteins have been reported to improve intestinal barrier function, but their mechanism of action is not clear. Recent studies, however, have demonstrated increased intestinal claudin expression in response to milk protein components. Reviewed here are new findings suggesting that whey-protein-derived transforming growth factor β transcriptionally upregulates claudin-4 expression via a Smad-4-dependent pathway. These and other data, including limited clinical studies, are summarized below and, in the aggregate, suggest a therapeutic role for whey protein in diseases of intestinal barrier dysfunction, perhaps, in part, by regulating claudin expression. © 2013 International Life Sciences Institute.

  5. A mechanism regulating G protein-coupled receptor signaling that requires cycles of protein palmitoylation and depalmitoylation.

    PubMed

    Jia, Lixia; Chisari, Mariangela; Maktabi, Mohammad H; Sobieski, Courtney; Zhou, Hao; Konopko, Aaron M; Martin, Brent R; Mennerick, Steven J; Blumer, Kendall J

    2014-02-28

    Reversible attachment and removal of palmitate or other long-chain fatty acids on proteins has been hypothesized, like phosphorylation, to control diverse biological processes. Indeed, palmitate turnover regulates Ras trafficking and signaling. Beyond this example, however, the functions of palmitate turnover on specific proteins remain poorly understood. Here, we show that a mechanism regulating G protein-coupled receptor signaling in neuronal cells requires palmitate turnover. We used hexadecyl fluorophosphonate or palmostatin B to inhibit enzymes in the serine hydrolase family that depalmitoylate proteins, and we studied R7 regulator of G protein signaling (RGS)-binding protein (R7BP), a palmitoylated allosteric modulator of R7 RGS proteins that accelerate deactivation of Gi/o class G proteins. Depalmitoylation inhibition caused R7BP to redistribute from the plasma membrane to endomembrane compartments, dissociated R7BP-bound R7 RGS complexes from Gi/o-gated G protein-regulated inwardly rectifying K(+) (GIRK) channels and delayed GIRK channel closure. In contrast, targeting R7BP to the plasma membrane with a polybasic domain and an irreversibly attached lipid instead of palmitate rendered GIRK channel closure insensitive to depalmitoylation inhibitors. Palmitate turnover therefore is required for localizing R7BP to the plasma membrane and facilitating Gi/o deactivation by R7 RGS proteins on GIRK channels. Our findings broaden the scope of biological processes regulated by palmitate turnover on specific target proteins. Inhibiting R7BP depalmitoylation may provide a means of enhancing GIRK activity in neurological disorders.

  6. Electrophysiology of Cranial Nerve Testing: Spinal Accessory and Hypoglossal Nerves.

    PubMed

    Stino, Amro M; Smith, Benn E

    2018-01-01

    Multiple techniques have been developed for the electrodiagnostic evaluation of cranial nerves XI and XII. Each of these carries both benefits and limitations, with more techniques and data being available in the literature for spinal accessory than hypoglossal nerve evaluation. Spinal accessory and hypoglossal neuropathy are relatively uncommon cranial mononeuropathies that may be evaluated in the outpatient electrodiagnostic laboratory setting. A review of available literature using PubMed was conducted regarding electrodiagnostic technique in the evaluation of spinal accessory and hypoglossal nerves searching for both routine nerve conduction studies and repetitive nerve conduction studies. The review provided herein provides a resource by which clinical neurophysiologists may develop and implement clinical and research protocols for the evaluation of both of these lower cranial nerves in the outpatient setting.

  7. Redox Regulation of Protein Kinases

    PubMed Central

    Truong, Thu H.; Carroll, Kate S.

    2015-01-01

    Protein kinases represent one of the largest families of genes found in eukaryotes. Kinases mediate distinct cellular processes ranging from proliferation, differentiation, survival, and apoptosis. Ligand-mediated activation of receptor kinases can lead to the production of endogenous H2O2 by membrane-bound NADPH oxidases. In turn, H2O2 can be utilized as a secondary messenger in signal transduction pathways. This review presents an overview of the molecular mechanisms involved in redox regulation of protein kinases and its effects on signaling cascades. In the first half, we will focus primarily on receptor tyrosine kinases (RTKs), whereas the latter will concentrate on downstream non-receptor kinases involved in relaying stimulant response. Select examples from the literature are used to highlight the functional role of H2O2 regarding kinase activity, as well as the components involved in H2O2 production and regulation during cellular signaling. In addition, studies demonstrating direct modulation of protein kinases by H2O2 through cysteine oxidation will be emphasized. Identification of these redox-sensitive residues may help uncover signaling mechanisms conserved within kinase subfamilies. In some cases, these residues can even be exploited as targets for the development of new therapeutics. Continued efforts in this field will further basic understanding of kinase redox regulation, and delineate the mechanisms involved in physiologic and pathological H2O2 responses. PMID:23639002

  8. Rab proteins: The key regulators of intracellular vesicle transport

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

    Bhuin, Tanmay; Roy, Jagat Kumar, E-mail: jkroy@bhu.ac.in

    2014-10-15

    Vesicular/membrane trafficking essentially regulates the compartmentalization and abundance of proteins within the cells and contributes in many signalling pathways. This membrane transport in eukaryotic cells is a complex process regulated by a large and diverse array of proteins. A large group of monomeric small GTPases; the Rabs are essential components of this membrane trafficking route. Most of the Rabs are ubiquitously expressed proteins and have been implicated in vesicle formation, vesicle motility/delivery along cytoskeleton elements and docking/fusion at target membranes through the recruitment of effectors. Functional impairments of Rabs affecting transport pathways manifest different diseases. Rab functions are accompanied bymore » cyclical activation and inactivation of GTP-bound and GDP-bound forms between the cytosol and membranes which is regulated by upstream regulators. Rab proteins are characterized by their distinct sub-cellular localization and regulate a wide variety of endocytic, transcytic and exocytic transport pathways. Mutations of Rabs affect cell growth, motility and other biological processes. - Highlights: • Rab proteins regulate different signalling pathways. • Deregulation of Rabs is the fundamental causes of a variety of human diseases. • This paper gives potential directions in developing therapeutic targets. • This paper also gives ample directions for modulating pathways central to normal physiology. • These are the huge challenges for drug discovery and delivery in near future.« less

  9. Teaching Techniques for Accessory Percussion

    ERIC Educational Resources Information Center

    Micallef, Ken

    2007-01-01

    Everyone is familiar with the main percussion instruments of the contemporary orchestra: bass drum, snare drum, suspended cymbal, vibraphone, and timpani. But as source material broadens, so do the demands placed on the percussion section. Accessory, or auxiliary percussion, can make the difference between a typical rendition of a well-known piece…

  10. Zyflamend Sensitizes Tumor Cells to TRAIL-Induced Apoptosis Through Up-Regulation of Death Receptors and Down-Regulation of Survival Proteins: Role of ROS-Dependent CCAAT/Enhancer-Binding Protein-Homologous Protein Pathway

    PubMed Central

    Kim, Ji Hye; Park, Byoungduck; Gupta, Subash C.; Kannappan, Ramaswamy; Sung, Bokyung

    2012-01-01

    Abstract Aim: TNF (tumor necrosis factor)-related apoptosis-inducing ligand (TRAIL), is a selective killer of tumor cells, although its potential is limited by the development of resistance. In this article, we investigated whether the polyherbal preparation Zyflamend® can sensitize tumor cells to TRAIL. Results: We found that Zyflamend potentiated TRAIL-induced apoptosis in human cancer cells. Zyflamend manifested its effects through several mechanisms. First, it down-regulated the expression of cell survival proteins known to be linked to resistance to TRAIL. Second, Zyflamend up-regulated the expression of pro-apoptotic protein, Bax. Third, Zyflamend up-regulated the expression of death receptors (DRs) for TRAIL. Up-regulation of DRs was critical as gene-silencing of these receptors significantly reduced the effect of Zyflamend on TRAIL-induced apoptosis. The up-regulation of DRs was dependent on CCAAT/enhancer-binding protein-homologous protein (CHOP), as Zyflamend induced CHOP, its gene-silencing abolished the induction of receptors, and mutation of the CHOP binding site on DR5 promoter abolished Zyflamend-mediated DR5 transactivation. Zyflamend mediated its effects through reactive oxygen species (ROS), as ROS quenching reduced its effect. Further, Zyflamend induced DR5 and CHOP and down-regulated the expression of cell survival proteins in nude mice bearing human pancreatic cancer cells. Innovation: Zyflamend can sensitize tumor cells to TRAIL through modulation of multiple cell signaling mechanisms that are linked to ROS. Conclusion: Zyflamend potentiates TRAIL-induced apoptosis through the ROS-CHOP-mediated up-regulation of DRs, increase in pro-apoptotic protein and down-regulation of cell survival proteins. Antioxid. Redox Signal. 16, 413–427. PMID:22004570

  11. Accessory renal arteries: Prevalence in resistant hypertension and an important role in nonresponse to radiofrequency renal denervation.

    PubMed

    VonAchen, Paige; Hamann, Jason; Houghland, Thomas; Lesser, John R; Wang, Yale; Caye, David; Rosenthal, Kristi; Garberich, Ross F; Daniels, Mary; Schwartz, Robert S

    The aim of this study was to understand the role of accessory renal arteries in resistant hypertension, and to establish their role in nonresponse to radiofrequency renal denervation (RDN) procedures. Prior studies suggest a role for accessory renal arteries in hypertensive syndromes, and recent clinical trials of renal denervation report that these anomalies are highly prevalent in resistant hypertension. This study evaluated the relationships among resistant hypertension, accessory renal arteries, and the response to radiofrequency (RF) renal denervation. Computed Tomography Angiography (CTA) and magnetic resonance imaging (MRI) scans from 58 patients with resistant hypertension undergoing RF renal denervation (RDN) were evaluated. Results were compared with CT scans in 57 healthy, normotensive subjects undergoing screening as possible renal transplant donors. All scans were carefully studied for accessory renal arteries, and were correlated with long term blood pressure reduction. Accessory renal arteries were markedly more prevalent in the hypertensive patients than normotensive renal donors (59% vs 32% respectively, p=0.004). RDN had an overall nonresponse rate of 29% (response rate 71%). Patients without accessory vessels had a borderline higher response rate to RDN than those with at least one accessory vessel (83% vs 62% respectively, p=0.076) and a higher RDN response than patients with untreated accessory arteries (83% vs 55%; p=0.040). For accessory renal arteries and nonresponse, the sensitivity was 76%, specificity 49%, with positive and negative predictive values 38% and 83% respectively. Accessory renal arteries were markedly over-represented in resistant hypertensives compared with healthy controls. While not all patients with accessory arteries were nonresponders, nonresponse was related to both the presence and non-treatment of accessory arteries. Addressing accessory renal arteries in future clinical trials may improve RDN therapeutic efficacy

  12. Clinical outcome of surgical treatment of the symptomatic accessory navicular.

    PubMed

    Kopp, Franz J; Marcus, Randall E

    2004-01-01

    When conservative treatment fails to provide relief for a symptomatic accessory navicular, surgical intervention may be necessary. Numerous studies have been published, reporting the results of the traditional Kidner procedure and alternative surgical techniques, all of which produce mostly satisfactory clinical outcomes. The purpose of this study was to report the clinical results, utilizing the American Orthopaedic Foot and Ankle Society (AOFAS) Midfoot Scale, of surgical management for symptomatic accessory navicular with simple excision and anatomic repair of the tibialis posterior tendon. The authors retrospectively reviewed the results of 13 consecutive patients (14 feet) who underwent surgical treatment for symptomatic accessory navicular. The patients ranged in age from 16 to 64 years (average, 34.1 years; mean, 28.2 years) at the time of surgery. All patients had a type II accessory navicular. The average follow-up of the patients involved in the study was 103.4 months (range, 45-194 months). The AOFAS Midfoot Scale was utilized to determine both preoperative and postoperative clinical status of the 14 feet included in the study. The average preoperative AOFAS score was 48.2 (range, 20-75; mean, 38.8). The average postoperative AOFAS score was 94.5 (range, 83-100; mean, 94.3). At last follow-up, 13 of 14 feet were without any pain, no patients had activity limitations, and only two of 14 feet required shoe insert modification. Postoperatively, no patients had a clinically notable change in their preoperative midfoot longitudinal arch alignment. All of the patients in the study were satisfied with the outcome of their surgery and would undergo the same operation again under similar circumstances. When conservative measures fail to relieve the symptoms of a painful accessory navicular, simple excision of the accessory navicular and anatomic repair of the posterior tibialis tendon is a successful intervention. Overall, the procedure provides reliable pain

  13. Role of the Accessory Parotid Gland in the Etiology of Parotitis: Statistical Analysis of Sialographic Features

    PubMed Central

    Zhu, Wangyong; Hu, Fengchun; Liu, Xingguang; Guo, Songcan; Tao, Qian

    2016-01-01

    This retrospective study aimed to identify if the existence of the accessory parotid gland correlated with the etiology of parotitis. This may aid the development of better treatment strategies in the future. Sialographic features of cases with parotitis and healthy subjects were reviewed. The chi-square test was used to compare the incidence of accessory parotid gland between the groups. The Student’s t test was used to compare the length of Stensen’s duct, the length from the orifice to the confluence of the accessory duct, and the angle between the accessory duct and Stensen’s duct between the groups. The incidence of accessory parotid gland in patients with parotitis was 71.8% (28/39), which was significantly higher than that in healthy subjects (P = 0.005). Patients with parotitis had a longer Stensen’s duct than healthy subjects (P = 0.003). There was no significant difference in the length from the orifice to the confluence of the accessory duct or the angle between the accessory duct and Stensen’s duct (P = 0.136 and 0.511, respectively) between the groups. The accessory parotid gland might play a role in the pathogenesis of parotitis. The existence of an accessory parotid gland is likely to interfere with salivary flow. Computational fluid dynamics analysis of salivary flow in the ductal system would be useful in future etiologic studies on parotitis. PMID:26913509

  14. Role of the Accessory Parotid Gland in the Etiology of Parotitis: Statistical Analysis of Sialographic Features.

    PubMed

    Zhu, Wangyong; Hu, Fengchun; Liu, Xingguang; Guo, Songcan; Tao, Qian

    2016-01-01

    This retrospective study aimed to identify if the existence of the accessory parotid gland correlated with the etiology of parotitis. This may aid the development of better treatment strategies in the future. Sialographic features of cases with parotitis and healthy subjects were reviewed. The chi-square test was used to compare the incidence of accessory parotid gland between the groups. The Student's t test was used to compare the length of Stensen's duct, the length from the orifice to the confluence of the accessory duct, and the angle between the accessory duct and Stensen's duct between the groups. The incidence of accessory parotid gland in patients with parotitis was 71.8% (28/39), which was significantly higher than that in healthy subjects (P = 0.005). Patients with parotitis had a longer Stensen's duct than healthy subjects (P = 0.003). There was no significant difference in the length from the orifice to the confluence of the accessory duct or the angle between the accessory duct and Stensen's duct (P = 0.136 and 0.511, respectively) between the groups. The accessory parotid gland might play a role in the pathogenesis of parotitis. The existence of an accessory parotid gland is likely to interfere with salivary flow. Computational fluid dynamics analysis of salivary flow in the ductal system would be useful in future etiologic studies on parotitis.

  15. Protein components of the microRNA pathway and human diseases

    PubMed Central

    Perron, Marjorie P.; Provost, Patrick

    2010-01-01

    Summary MicroRNAs (miRNAs) are key regulators of messenger RNA (mRNA) translation known to be involved in a wide variety of cellular processes. In fact, their individual importance is reflected in the diseases that may arise upon the loss, mutation or dysfunction of specific miRNAs. It has been appreciated only recently that diseases may also develop when the protein components of the miRNA machinery itself are affected. The core enzymes of the major protein complexes involved in miRNA biogenesis and function, such as the ribonucleases III (RNases III) Drosha and Dicer as well as Argonaute 2 (Ago2), appear to be essential. However, the accessory proteins of the miRNA pathway, such as the DiGeorge syndrome critical region gene 8 (DGCR8) protein, Exportin-5 (Exp-5), TAR RNA binding protein (TRBP) and Fragile X mental retardation protein (FMRP), are each related, in various ways, to specific genetic diseases. PMID:19301657

  16. Dusp5 negatively regulates IL-33-mediated eosinophil survival and function

    PubMed Central

    Holmes, Derek A; Yeh, Jung-Hua; Yan, Donghong; Xu, Min; Chan, Andrew C

    2015-01-01

    Mitogen-activated protein kinase (MAPK) activation controls diverse cellular functions including cellular survival, proliferation, and apoptosis. Tuning of MAPK activation is counter-regulated by a family of dual-specificity phosphatases (DUSPs). IL-33 is a recently described cytokine that initiates Th2 immune responses through binding to a heterodimeric IL-33Rα (ST2L)/IL-1α accessory protein (IL-1RAcP) receptor that coordinates activation of ERK and NF-κB pathways. We demonstrate here that DUSP5 is expressed in eosinophils, is upregulated following IL-33 stimulation and regulates IL-33 signaling. Dusp5−/− mice have prolonged eosinophil survival and enhanced eosinophil effector functions following infection with the helminth Nippostrongylus brasiliensis. IL-33-activated Dusp5−/− eosinophils exhibit increased cellular ERK1/2 activation and BCL-XL expression that results in enhanced eosinophil survival. In addition, Dusp5−/− eosinophils demonstrate enhanced IL-33-mediated activation and effector functions. Together, these data support a role for DUSP5 as a novel negative regulator of IL-33-dependent eosinophil function and survival. PMID:25398911

  17. An Accessory Muscle of Pectoral Region: A Case Report

    PubMed Central

    Bannur, B.M.; Mallashetty, Nagaraj; Endigeri, Preetish

    2013-01-01

    Among the variations of pectoral muscles, this case appears to be unique in the literature. This was a case of an accessory pectoral muscle which was located between pectoralis major and pectoralis minor muscles, which was discovered during a routine anatomy dissection. The accessory muscle originated from 6th and 7th ribs at costo-chondral junction, which travelled supero-laterally and inserted by fusing with fibres of pectoralis minor. This unusual muscle holds importance for surgeons while they perform dissectomies, in avoiding complications. PMID:24179919

  18. Tor1 regulates protein solubility in Saccharomyces cerevisiae

    PubMed Central

    Peters, Theodore W.; Rardin, Matthew J.; Czerwieniec, Gregg; Evani, Uday S.; Reis-Rodrigues, Pedro; Lithgow, Gordon J.; Mooney, Sean D.; Gibson, Bradford W.; Hughes, Robert E.

    2012-01-01

    Accumulation of insoluble protein in cells is associated with aging and aging-related diseases; however, the roles of insoluble protein in these processes are uncertain. The nature and impact of changes to protein solubility during normal aging are less well understood. Using quantitative mass spectrometry, we identify 480 proteins that become insoluble during postmitotic aging in Saccharomyces cerevisiae and show that this ensemble of insoluble proteins is similar to those that accumulate in aging nematodes. SDS-insoluble protein is present exclusively in a nonquiescent subpopulation of postmitotic cells, indicating an asymmetrical distribution of this protein. In addition, we show that nitrogen starvation of young cells is sufficient to cause accumulation of a similar group of insoluble proteins. Although many of the insoluble proteins identified are known to be autophagic substrates, induction of macroautophagy is not required for insoluble protein formation. However, genetic or chemical inhibition of the Tor1 kinase is sufficient to promote accumulation of insoluble protein. We conclude that target of rapamycin complex 1 regulates accumulation of insoluble proteins via mechanisms acting upstream of macroautophagy. Our data indicate that the accumulation of proteins in an SDS-insoluble state in postmitotic cells represents a novel autophagic cargo preparation process that is regulated by the Tor1 kinase. PMID:23097491

  19. Headgear Accessories Classification Using an Overhead Depth Sensor

    PubMed Central

    Luna, Carlos A.; Marron-Romera, Marta; Mazo, Manuel; Luengo-Sanchez, Sara; Macho-Pedroso, Roberto

    2017-01-01

    In this paper, we address the generation of semantic labels describing the headgear accessories carried out by people in a scene under surveillance, only using depth information obtained from a Time-of-Flight (ToF) camera placed in an overhead position. We propose a new method for headgear accessories classification based on the design of a robust processing strategy that includes the estimation of a meaningful feature vector that provides the relevant information about the people’s head and shoulder areas. This paper includes a detailed description of the proposed algorithmic approach, and the results obtained in tests with persons with and without headgear accessories, and with different types of hats and caps. In order to evaluate the proposal, a wide experimental validation has been carried out on a fully labeled database (that has been made available to the scientific community), including a broad variety of people and headgear accessories. For the validation, three different levels of detail have been defined, considering a different number of classes: the first level only includes two classes (hat/cap, and no hat/cap), the second one considers three classes (hat, cap and no hat/cap), and the last one includes the full class set with the five classes (no hat/cap, cap, small size hat, medium size hat, and large size hat). The achieved performance is satisfactory in every case: the average classification rates for the first level reaches 95.25%, for the second one is 92.34%, and for the full class set equals 84.60%. In addition, the online stage processing time is 5.75 ms per frame in a standard PC, thus allowing for real-time operation. PMID:28796177

  20. 21 CFR 884.1720 - Gynecologic laparoscope and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... accessory instruments include: the lens cleaning brush, biopsy brush, clip applier (without clips...), retractor, mechanical (noninflatable), snare, stylet, forceps, dissector, mechanical (noninflatable...

  1. 21 CFR 884.1720 - Gynecologic laparoscope and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... accessory instruments include: the lens cleaning brush, biopsy brush, clip applier (without clips...), retractor, mechanical (noninflatable), snare, stylet, forceps, dissector, mechanical (noninflatable...

  2. 21 CFR 884.1720 - Gynecologic laparoscope and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... accessory instruments include: the lens cleaning brush, biopsy brush, clip applier (without clips...), retractor, mechanical (noninflatable), snare, stylet, forceps, dissector, mechanical (noninflatable...

  3. The role of accessory cells in polyclonal T cell activation. I. Both induction of interleukin 2 production and of interleukin 2 responsiveness by concanavalin A are accessory cell dependent.

    PubMed

    Hünig, T; Loos, M; Schimpl, A

    1983-01-01

    Recent studies from other laboratories have shown that concanavalin A (Con A) acts at two separate steps in polyclonal T cell activation: interleukin 2 (IL2) production, and induction of responsiveness to IL2. Using a combination of techniques for the depletion of accessory cells from lymph node T cells, we have investigated which of these steps, if not both, is responsible for the known requirement for accessory cells in the Con A response. It was found that with increasing T cell purification, first the ability is lost to produce sufficient levels of endogenous IL2, whereas induction of IL2 responsiveness can still take place. Further removal of accessory cells however yields a population of resting T cells that cannot be induced by Con A to become IL2-reactive. It was concluded that both IL2 production and induction of reactivity to IL2 are accessory cell-dependent events.

  4. Molecular switch-like regulation in motor proteins.

    PubMed

    Tafoya, Sara; Bustamante, Carlos

    2018-06-19

    Motor proteins are powered by nucleotide hydrolysis and exert mechanical work to carry out many fundamental biological tasks. To ensure their correct and efficient performance, the motors' activities are allosterically regulated by additional factors that enhance or suppress their NTPase activity. Here, we review two highly conserved mechanisms of ATP hydrolysis activation and repression operating in motor proteins-the glutamate switch and the arginine finger-and their associated regulatory factors. We examine the implications of these regulatory mechanisms in proteins that are formed by multiple ATPase subunits. We argue that the regulatory mechanisms employed by motor proteins display features similar to those described in small GTPases, which require external regulatory elements, such as dissociation inhibitors, exchange factors and activating proteins, to switch the protein's function 'on' and 'off'. Likewise, similar regulatory roles are taken on by the motor's substrate, additional binding factors, and even adjacent subunits in multimeric complexes. However, in motor proteins, more than one regulatory factor and the two mechanisms described here often underlie the machine's operation. Furthermore, ATPase regulation takes place throughout the motor's cycle, which enables a more complex function than the binary 'active' and 'inactive' states.This article is part of a discussion meeting issue 'Allostery and molecular machines'. © 2018 The Author(s).

  5. Modeling and Simulation of Two Wheelchair Accessories for Pushing Doors.

    PubMed

    Abdullah, Soran Jalal; Shaikh Mohammed, Javeed

    2017-03-27

    Independent mobility is vital to individuals of all ages, and wheelchairs have proven to be great personal mobility devices. The tasks of opening and navigating through a door are trivial for healthy people, while the same tasks could be difficult for some wheelchair users. A wide range of intelligent wheelchair controllers and systems, robotic arms, or manipulator attachments integrated with wheelchairs have been developed for various applications, including manipulating door knobs. Unfortunately, the intelligent wheelchairs and robotic attachments are not widely available as commercial products. Therefore, the current manuscript presents the modeling and simulation of a novel but simple technology in the form of a passive wheelchair accessory (straight, arm-like with a single wheel, and arc-shaped with multiple wheels) for pushing doors open from a wheelchair. From the simulations using different wheel shapes and sizes, it was found that the arc-shaped accessory could push open the doors faster and with almost half the required force as compared to the arm-like accessory. Also, smaller spherical wheels were found to be best in terms of reaction forces on the wheels. Prototypes based on the arc-shaped accessory design will be manufactured and evaluated for pushing doors open and dodging or gliding other obstacles.

  6. Transcriptome analysis to identify genes for peptides and proteins involved in immunity and reproduction from male accessory glands and ejaculatory duct of Bactrocera dorsalis.

    PubMed

    Wei, Dong; Tian, Chuan-Bei; Liu, Shi-Huo; Wang, Tao; Smagghe, Guy; Jia, Fu-Xian; Dou, Wei; Wang, Jin-Jun

    2016-06-01

    In the male reproductive system of insects, the male accessory glands and ejaculatory duct (MAG/ED) are important organs and their primary function is to enhance the fertility of spermatozoa. Proteins secreted by the MAG/ED are also known to induce post-mating changes and immunity responses in the female insect. To understand the gene expression profile in the MAG/ED of the oriental fruit fly Bactrocera dorsalis (Hendel), that is an important pest in fruits, we performed an Illumina-based deep sequencing of mRNA. This yielded 54,577,630 clean reads corresponding to 4.91Gb total nucleotides that were assembled and clustered to 30,669 unigenes (average 645bp). Among them, 20,419 unigenes were functionally annotated to known proteins/peptides in Gene Orthology, Clusters of Orthologous Groups, Kyoto Encyclopedia of Genes and Genomes pathway databases. Typically, many genes were involved in immunity and these included microbial recognition proteins and antimicrobial peptides. Subsequently, the inducible expression of these immunity-related genes was confirmed by qRT-PCR analysis when insects were challenged with immunity-inducible factors, suggesting their function in guaranteeing fertilization success. Besides, we identified some important reproductive genes such as juvenile hormone- and ecdysteroid-related genes in this de novo assembly. In conclusion, this transcriptomic sequencing of B. dorsalis MAG/ED provides insights to facilitate further functional research of reproduction, immunity and molecular evolution of reproductive proteins in this important agricultural pest. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Adolescent accessory navicular.

    PubMed

    Leonard, Zachary C; Fortin, Paul T

    2010-06-01

    Accessory tarsal navicular is a common anomaly in the human foot. It should be in the differential of medial foot pain. A proper history and physical, along with imaging modalities, can lead to the diagnosis. Often, classification of the ossicle and amount of morbidity guide treatment. Nonsurgical measures can provide relief. A variety of surgical procedures have been used with good results. Our preferred method is excision for small ossicles and segmental fusion after removal of the synchondrosis for large ossicles. In addition, pes planovalgus deformities need to be addressed concomitantly. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Variations in the surface anatomy of the spinal accessory nerve in the posterior triangle.

    PubMed

    Symes, A; Ellis, H

    2005-12-01

    Iatrogenic injury to the spinal accessory nerve has been widely documented and can have medico-legal implications. The resulting syndrome of pain, paralysis and winging of the scapula are often the source of considerable morbidity. This paper researches the degree of accuracy achievable in mapping the surface anatomy of the spinal accessory nerve in the region of the posterior triangle with a view to creating a cartographical aid to surgical procedures. The necks of 25 adult cadavers were dissected bilaterally to expose the spinal accessory nerve. Variations in the course and distribution of the spinal accessory nerve in the posterior triangle were recorded along with its relationship to the borders of sternocleidomastoid and trapezius. Considerable variation was seen in the surface and regional anatomy of the nerve and in the contribution of the cervical plexus to the spinal accessory nerve in the posterior triangle. Measurements of the running course and exit point of the nerve into and from the posterior triangle differed significantly from those previously recorded. Delineation of an accurate surface anatomy was not possible. Creating a map to define the surface anatomy of the spinal accessory nerve in the posterior triangle is an unrealistic goal given its wide variations in man. Avoidance of damage to the spinal accessory nerve cannot be achieved by slavishly adhering to surface markings given in textbooks, but only by cautious dissection during operations on the posterior triangle.

  9. 21 CFR 890.3910 - Wheelchair accessory.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Wheelchair accessory. 890.3910 Section 890.3910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3910 Wheelchair...

  10. 21 CFR 890.3910 - Wheelchair accessory.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Wheelchair accessory. 890.3910 Section 890.3910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3910 Wheelchair...

  11. 21 CFR 890.3910 - Wheelchair accessory.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Wheelchair accessory. 890.3910 Section 890.3910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3910 Wheelchair...

  12. 21 CFR 890.3910 - Wheelchair accessory.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Wheelchair accessory. 890.3910 Section 890.3910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3910 Wheelchair...

  13. 21 CFR 890.3910 - Wheelchair accessory.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Wheelchair accessory. 890.3910 Section 890.3910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3910 Wheelchair...

  14. Photoreactive synthetic regulator of protein function and methods of use thereof

    DOEpatents

    Trauner, Dirk; Isacoff, Ehud Y; Kramer, Richard H; Banghart, Matthew R; Fortin, Doris L; Mourot, Alexandre

    2015-03-31

    The present disclosure provides a photoreactive synthetic regulator of protein function. The present disclosure further provides a light-regulated polypeptide that includes a subject synthetic regulator. Also provided are cells and membranes comprising a subject light-regulated polypeptide. The present disclosure further provides methods of modulating protein function, involving use of light.

  15. Melanocortin 3 Receptor Has a 5′ Exon That Directs Translation of Apically Localized Protein From the Second In-Frame ATG

    PubMed Central

    Park, Jeenah; Sharma, Neeraj

    2014-01-01

    Melanocortin-3 receptor (MC3R) is a canonical MSH receptor that plays an essential role in energy homeostasis. Variants in MC3R have been implicated in obesity in humans and mice. However, interpretation of the functional consequences of these variants is challenging because the translational start site of MC3R is unclear. Using 5′ rapid amplification of cDNA ends, we discovered a novel upstream exon that extends the length of the 5′ untranslated region (UTR) in MC3R without changing the open-reading frame. The full-length 5′ UTR directs utilization of an evolutionarily conserved second in-frame ATG as the primary translation start site. MC3R synthesized from the second ATG is localized to apical membranes of polarized Madin-Darby canine kidney cells, consistent with its function as a cell surface mediator of melanocortin signaling. Expression of MC3R causes relocalization of melanocortin receptor accessory protein 2, an accessory factor for melanocortin-2 receptor, to the apical membrane, coincident with the location of MC3R. In contrast, protein synthesized from MC3R cDNAs lacking the 5′ UTR displayed diffuse cytosolic distribution and has no effect on the distribution of melanocortin receptor accessory protein 2. Our findings demonstrate that a previously unannotated 5′ exon directs translation of MC3R protein that localizes to apical membranes of polarized cells. Together, our work provides insight on the structure of human MC3R and reveals a new pathway for regulation of energy metabolism. PMID:25051171

  16. 29 CFR 1919.28 - Unit proof tests-cranes and gear accessory thereto.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Unit proof tests-cranes and gear accessory thereto. 1919.28... ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) GEAR CERTIFICATION Certification of Vessels: Tests and Proof Loads; Heat Treatment; Competent Persons § 1919.28 Unit proof tests—cranes and gear accessory thereto...

  17. Current opinion in Microbiology Roles of adaptor proteins in regulation of bacterial proteolysis

    PubMed Central

    Battesti, Aurelia; Gottesman, Susan

    2013-01-01

    Elimination of non-functional or unwanted proteins is critical for cell growth and regulation. In bacteria, ATP-dependent proteases target cytoplasmic proteins for degradation, contributing to both protein quality control and regulation of specific proteins, thus playing roles parallel to that of the proteasome in eukaryotic cells. Adaptor proteins provide a way to modulate the substrate specificity of the proteases and allow regulated proteolysis. Advances over the past few years have provided new insight into how adaptor proteins interact with both substrates and proteases and how adaptor functions are regulated. An important advance has come with the recognition of the critical roles of anti-adaptor proteins in regulating adaptor availability. PMID:23375660

  18. Comparative anatomy of the accessory ciliary ganglion in mammals.

    PubMed

    Kuchiiwa, S; Kuchiiwa, T; Suzuki, T

    1989-01-01

    The orbits of 13 mammalian species (pig, sika deer, domestic sheep, horse, cat, fox, racoon dog, marten, rat, rabbit, crab-eating macaque, japanese macaque and man) were stained with silver nitrate and dissected under a dissecting microscope with special attention to the presence and location of the accessory ciliary ganglion. Some preparations were stained with thionin and examined as whole-mounts in a transmission microscope. The accessory ciliary ganglion was present in all 13 species, although the number and degree of development varied greatly from species to species. The accessory ciliary ganglion could be readily differentiated from the main ciliary ganglion in the following respects: it was located on the short ciliary nerve, and it had no root derived directly from the inferior trunk of the oculomotor nerve and it never attaches to this nerve. In many species, ganglion cells were also scattered in the short ciliary nerves in the stained whole preparations. In a few species, there were one or more small ganglia on the nerve to the inferior oblique muscle.

  19. Variation in sperm displacement and its association with accessory gland protein loci in Drosophila melanogaster.

    PubMed

    Clark, A G; Aguadé, M; Prout, T; Harshman, L G; Langley, C H

    1995-01-01

    Genes that influence mating and/or fertilization success may be targets for strong natural selection. If females remate frequently relative to the duration of sperm storage and rate of sperm use, sperm displacement may be an important component of male reproductive success. Although it has long been known that mutant laboratory stocks of Drosophila differ in sperm displacement, the magnitude of the naturally occurring genetic variation in this character has not been systematically quantified. Here we report the results of a screen for variation in sperm displacement among 152 lines of Drosophilia melanogaster that were made homozygous for second and/or third chromosomes recovered from natural populations. Sperm displacement was assayed by scoring the progeny of cn;bw females that had been mated sequentially to cn;bw and tested males in either order. Highly significant differences were seen in both the ability to displace sperm that is resident in the female's reproductive tract and in the ability to resist displacement by subsequent sperm. Most lines exhibited nearly complete displacement, having nearly all progeny sired by the second male, but several lines had as few as half the progeny fathered by the second male. Lines that were identified in the screen for naturally occurring variation in sperm displacement were also characterized for single-strand conformation polymorphisms (SSCP) at seven accessory gland protein (Acp) genes, Glucose dehydrogenase (Gld), and Esterase-6 (Est-6). Acp genes encode proteins that are in some cases known to be transmitted to the female in the seminal fluid and are likely candidates for genes that might mediate the phenomenon of sperm displacement. Significant associations were found between particular Acp alleles at four different loci (Acp26Aa/Ab, Acp29B, Acp36DE and Acp53E) and the ability of males to resist displacement by subsequent sperm. There was no correlation between the ability to displace resident sperm and the ability

  20. Hormonal regulation of platypus Beta-lactoglobulin and monotreme lactation protein genes.

    PubMed

    Enjapoori, Ashwantha Kumar; Lefèvre, Christophe M; Nicholas, Kevin R; Sharp, Julie A

    2017-02-01

    Endocrine regulation of milk protein gene expression in marsupials and eutherians is well studied. However, the evolution of this complex regulation that began with monotremes is unknown. Monotremes represent the oldest lineage of extant mammals and the endocrine regulation of lactation in these mammals has not been investigated. Here we characterised the proximal promoter and hormonal regulation of two platypus milk protein genes, Beta-lactoglobulin (BLG), a whey protein and monotreme lactation protein (MLP), a monotreme specific milk protein, using in vitro reporter assays and a bovine mammary epithelial cell line (BME-UV1). Insulin and dexamethasone alone provided partial induction of MLP, while the combination of insulin, dexamethasone and prolactin was required for maximal induction. Partial induction of BLG was achieved by insulin, dexamethasone and prolactin alone, with maximal induction using all three hormones. Platypus MLP and BLG core promoter regions comprised transcription factor binding sites (e.g. STAT5, NF-1 and C/EBPα) that were conserved in marsupial and eutherian lineages that regulate caseins and whey protein gene expression. Our analysis suggests that insulin, dexamethasone and/or prolactin alone can regulate the platypus MLP and BLG gene expression, unlike those of therian lineage. The induction of platypus milk protein genes by lactogenic hormones suggests they originated before the divergence of marsupial and eutherians. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Gene regulation by the VirS/VirR system in Clostridium perfringens.

    PubMed

    Ohtani, Kaori

    2016-10-01

    The Gram-positive anaerobic spore-forming rod, Clostridium perfringens, is widely distributed in nature, especially in soil and the gastrointestinal tract of humans and animals. C. perfringens produces many secreted toxins and enzymes that are involved in the pathogenesis of gas gangrane and gastrointestinal disease. One of the most important systems regulating the production of these proteins in C. perfringens is the VirS/VirR-VR-RNA signal transduction cascade. The Agr system also important for the regulation of toxin genes. VirS appears to sense the peptide produced by the Agr (accessory gene regulator) system. The VirS/VirR-VR-RNA cascade controls the pathogenesis of C. perfringens infections by regulating virulence related genes and genes for energy metabolism. These systems are important for the host cell-induced upregulation of toxin production. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Diverse Broad-Host-Range Plasmids from Freshwater Carry Few Accessory Genes

    PubMed Central

    Sen, Diya; Yano, Hirokazu; Bauer, Matthew L.; Rogers, Linda M.; Van der Auwera, Geraldine A.

    2013-01-01

    Broad-host-range self-transferable plasmids are known to facilitate bacterial adaptation by spreading genes between phylogenetically distinct hosts. These plasmids typically have a conserved backbone region and a variable accessory region that encodes host-beneficial traits. We do not know, however, how well plasmids that do not encode accessory functions can survive in nature. The goal of this study was to characterize the backbone and accessory gene content of plasmids that were captured from freshwater sources without selecting for a particular phenotype or cultivating their host. To do this, triparental matings were used such that the only required phenotype was the plasmid's ability to mobilize a nonconjugative plasmid. Based on complete genome sequences of 10 plasmids, only 5 carried identifiable accessory gene regions, and none carried antibiotic resistance genes. The plasmids belong to four known incompatibility groups (IncN, IncP-1, IncU, and IncW) and two potentially new groups. Eight of the plasmids were shown to have a broad host range, being able to transfer into alpha-, beta-, and gammaproteobacteria. Because of the absence of antibiotic resistance genes, we resampled one of the sites and compared the proportion of captured plasmids that conferred antibiotic resistance to their hosts with the proportion of such plasmids captured from the effluent of a local wastewater treatment plant. Few of the captured plasmids from either site encoded antibiotic resistance. A high diversity of plasmids that encode no or unknown accessory functions is thus readily found in freshwater habitats. The question remains how the plasmids persist in these microbial communities. PMID:24096417

  3. Anoctamin 6 Contributes to Cl− Secretion in Accessory Cholera Enterotoxin (Ace)-stimulated Diarrhea

    PubMed Central

    Aoun, Joydeep; Hayashi, Mikio; Sheikh, Irshad Ali; Sarkar, Paramita; Saha, Tultul; Ghosh, Priyanka; Bhowmick, Rajsekhar; Ghosh, Dipanjan; Chatterjee, Tanaya; Chakrabarti, Pinak; Chakrabarti, Manoj K.; Hoque, Kazi Mirajul

    2016-01-01

    Accessory cholera enterotoxin (Ace) of Vibrio cholerae has been shown to contribute to diarrhea. However, the signaling mechanism and specific type of Cl− channel activated by Ace are still unknown. We have shown here that the recombinant Ace protein induced ICl of apical plasma membrane, which was inhibited by classical CaCC blockers. Surprisingly, an Ace-elicited rise of current was neither affected by ANO1 (TMEM16A)-specific inhibitor T16A(inh)-AO1(TAO1) nor by the cystic fibrosis transmembrane conductance regulator (CFTR) blocker, CFTR inh-172. Ace stimulated whole-cell current in Caco-2 cells. However, the apical ICl was attenuated by knockdown of ANO6 (TMEM16F). This impaired phenotype was restored by re-expression of ANO6 in Caco-2 cells. Whole-cell patch clamp recordings of ANO currents in HEK293 cells transiently expressing mouse ANO1-mCherry or ANO6-GFP confirmed that Ace induced Cl− secretion. Application of Ace produced ANO6 but not the ANO1 currents. Ace was not able to induce a [Ca2+]i rise in Caco-2 cells, but cellular abundance of phosphatidylinositol 4,5-bisphosphate (PIP2) increased. Identification of the PIP2-binding motif at the N-terminal sequence among human and mouse ANO6 variants along with binding of PIP2 directly to ANO6 in HEK293 cells indicate likely PIP2 regulation of ANO6. The biophysical and pharmacological properties of Ace stimulated Cl− current along with intestinal fluid accumulation, and binding of PIP2 to the proximal KR motif of channel proteins, whose mutagenesis correlates with altered binding of PIP2, is comparable with ANO6 stimulation. We conclude that ANO6 is predominantly expressed in intestinal epithelia, where it contributes secretory diarrhea by Ace stimulation in a calcium-independent mechanism of RhoA-ROCK-PIP2 signaling. PMID:27799301

  4. 47 CFR 15.27 - Special accessories.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Special accessories. 15.27 Section 15.27 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL RADIO FREQUENCY DEVICES General § 15.27 Special... manual is provided only in a form other than paper, such as on a computer disk or over the Internet, the...

  5. 47 CFR 15.27 - Special accessories.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false Special accessories. 15.27 Section 15.27 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL RADIO FREQUENCY DEVICES General § 15.27 Special... manual is provided only in a form other than paper, such as on a computer disk or over the Internet, the...

  6. 47 CFR 15.27 - Special accessories.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false Special accessories. 15.27 Section 15.27 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL RADIO FREQUENCY DEVICES General § 15.27 Special... manual is provided only in a form other than paper, such as on a computer disk or over the Internet, the...

  7. 47 CFR 15.27 - Special accessories.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Special accessories. 15.27 Section 15.27 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL RADIO FREQUENCY DEVICES General § 15.27 Special... manual is provided only in a form other than paper, such as on a computer disk or over the Internet, the...

  8. 29 CFR 1919.28 - Unit proof tests-cranes and gear accessory thereto.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 7 2011-07-01 2011-07-01 false Unit proof tests-cranes and gear accessory thereto. 1919.28... Loads; Heat Treatment; Competent Persons § 1919.28 Unit proof tests—cranes and gear accessory thereto. (a) Except as noted in paragraph (e) of this section, cranes and other hoisting machines, together...

  9. R4 RGS Proteins: Regulation of G Protein Signaling and Beyond

    PubMed Central

    Bansal, Geetanjali; Druey, Kirk M.; Xie, Zhihui

    2007-01-01

    The Regulators of G protein Signaling (RGS) proteins were initially characterized as inhibitors of signal transduction cascades initiated by G-protein-coupled receptors (GPCRs) because of their ability to increase the intrinsic GTPase activity of heterotrimeric G proteins. This GTPase accelerating (GAP) activity enhances G protein deactivation and promotes desensitization. However, in addition to this signature trait, emerging data have revealed an expanding network of proteins, lipids, and ions that interact with RGS proteins and confer additional regulatory functions. This review highlights recent advances in our understanding of the physiological functions of one subfamily of RGS proteins with a high degree of homology (B/R4) gleaned from recent studies of knockout mice or cells with reduced RGS expression. We also discuss some of the newly-appreciated interactions of RGS proteins with cellular factors that suggest RGS control of several components of G-protein-mediated pathways as well as a diverse array of non-GPCR-mediated biological responses. PMID:18006065

  10. Accessory Axillary Breast Excision with Liposuction Using Minimal Incision: A Preliminary Report.

    PubMed

    Hwang, Seong Bae; Choi, Byung Seo; Byun, Geon Young; Koo, Bum Hwan; Lee, Sung Ryul

    2017-02-01

    Accessory breasts have received little attention in the surgical fields, although the condition is quite common in the female population, with 2-6% of women suffering from it. Its convexity and cyclic pain make women feel embarrassed and uncomfortable, so patients often desire surgical excision to improve their appearances and to remove the pain. A total of 967 patients who had been treated by an excision of accessory breast tissue with liposuction using minimal incision from September 2013 to Dec 2015 at the Damsoyu Hospital were analyzed for clinical factors retrospectively. All 967 patients were female. There were 514 (53.2%) unmarried patients and 453 (46.8%) married patients. The major clinical manifestation was the problem in the appearance with cyclic pain in both unmarried and married groups (82.7 vs. 87.9%). Three types of accessory breasts were observed: 779 (80.6%) breast tissue only in axillae, 182 (18.8%) breast tissue with accessory nipple, and 6 (0.6%) breast tissue with accessory nipple-areolar complex. The mean operation time was 58 min. All cyclic axillar pain in our cases was resolved after the operation. Postoperative complications developed in 160 patients (16.55%). Among them, seroma after operation was the most common (11.27%). In our study, 95.65% of the patients were satisfied with the cosmetic outcomes. The surgical excision of accessory breasts with liposuction through the minimal incision is a safe and effective method to make women feel comfortable in clinical manifestations and be satisfied with their cosmetic axillar line. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  11. Electrophysiological mapping of the accessory olfactory bulb of the rabbit (Oryctolagus cuniculus).

    PubMed

    van Groen, T; Ruardy, L; da Silva, F H

    1986-07-01

    Field potentials elicited by electrical stimulation of the vomeronasal nerve were measured in the accessory olfactory bulb of the rabbit. Maps were made of the distribution of surface field potentials and of the corresponding depth profiles. The surface maps followed closely the contours of the accessory olfactory bulb: at the frontal border the field potential tended to zero and at the center of the structure the field potential attained a maximum. Depth profiles of the field potentials through the accessory olfactory bulb presented a surface-negative wave and, in depth, a positive wave. The polarity reversal occurred at the deep part of the granule cell layer. The zero equipotential line followed closely the curvature of the granule cell layer. Current source density analysis of the depth profiles revealed a main sink at the external plexiform and granule cell layers. This indicates that the main activity in the accessory olfactory bulb is generated by the synapses between the mitral cells and the granule cells as is found in the main olfactory bulb.

  12. Spinal Accessory Motor Neurons in the Mouse: A Special Type of Branchial Motor Neuron?

    PubMed

    Watson, Charles; Tvrdik, Petr

    2018-04-16

    The spinal accessory nerve arises from motor neurons in the upper cervical spinal cord. The axons of these motor neurons exit dorsal to the ligamentum denticulatum and form the spinal accessory nerve. The nerve ascends in the spinal subarachnoid space to enter the posterior cranial fossa through the foramen magnum. The spinal accessory nerve then turns caudally to exit through the jugular foramen alongside the vagus and glossopharyngeal nerves, and then travels to supply the sternomastoid and trapezius muscles in the neck. The unusual course of the spinal accessory nerve has long prompted speculation that it is not a typical spinal motor nerve and that it might represent a caudal remnant of the branchial motor system. Our cell lineage tracing data, combined with images from public databases, show that the spinal accessory motor neurons in the mouse transiently express Phox2b, a transcription factor that is required for development of brain stem branchial motor nuclei. While this is strong prima facie evidence that the spinal accessory motor neurons should be classified as branchial motor, the evolutionary history of these motor neurons in anamniote vertebrates suggests that they may be considered to be an atypical branchial group that possesses both branchial and somatic characteristics. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  13. 21 CFR 884.4100 - Endoscopic electrocautery and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... coagulate fallopian tube tissue with a probe heated by low-voltage energy. This generic type of device may include the following accessories: electrical generators, probes, and electrical cables. (b...

  14. 21 CFR 884.4100 - Endoscopic electrocautery and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... coagulate fallopian tube tissue with a probe heated by low-voltage energy. This generic type of device may include the following accessories: electrical generators, probes, and electrical cables. (b...

  15. 21 CFR 884.4100 - Endoscopic electrocautery and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... coagulate fallopian tube tissue with a probe heated by low-voltage energy. This generic type of device may include the following accessories: electrical generators, probes, and electrical cables. (b...

  16. 21 CFR 884.4100 - Endoscopic electrocautery and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... coagulate fallopian tube tissue with a probe heated by low-voltage energy. This generic type of device may include the following accessories: electrical generators, probes, and electrical cables. (b...

  17. 21 CFR 884.1720 - Gynecologic laparoscope and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... genital organs. This generic type of device may include: Trocar and cannula, instruments used through an... accessory instruments include: the lens cleaning brush, biopsy brush, clip applier (without clips...

  18. 21 CFR 884.1720 - Gynecologic laparoscope and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... genital organs. This generic type of device may include: Trocar and cannula, instruments used through an... accessory instruments include: the lens cleaning brush, biopsy brush, clip applier (without clips...

  19. Reconstructive surgery using interference screw fixation for painful accessory navicular in adult athletes.

    PubMed

    Miyamoto, Wataru; Takao, Masato; Yamada, Kazuaki; Yasui, Youichi; Matsushita, Takashi

    2012-10-01

    To examine the effectiveness of a new technique for reattaching the posterior tibial tendon (PTT) using a bone tunnel and interference screw after resection of the accessory navicular for painful accessory navicular (type II) in adult athletes. Ten adult athletes (7 male, 3 female; mean age 30 years, range 23-45) underwent reconstruction using a bone tunnel with an interference screw for a painful accessory navicular. All patients complained of pain on the medial aspect of the foot after eversion sprain during sports activities and radiographs revealed type II accessory navicular. Clinical evaluation with the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS) and visual analogue scale (VAS) before surgery was compared with that at most recent follow up (mean 30 months, range 24-39). Mean AOFAS score improved from a preoperative 62.8 ± 2.9 points (range 61-82) to a postoperative 92.1 ± 7.0 points (range 83-100; p < 0.01). Furthermore, mean VAS score improved from a preoperative 92.5 ± 5.4 points (range 85-100) to a postoperative 4.5 ± 3.8 points (range 0-10; p < 0.01). All patients could return to full sports activity at a mean of 14 weeks (range 12-18) after surgery. The presented technique reconstructs the bone-tendon interface of the PTT at the primary navicular with sufficient fixation after resection of the accessory navicular, which preserves the strength of the PTT in adult athletes with an intractably painful accessory navicular.

  20. Comparative proteomic analyses reveal that the regulators of G-protein signaling proteins regulate amino acid metabolism of the rice blast fungus Magnaporthe oryzae.

    PubMed

    Zhang, Haifeng; Ma, Hongyu; Xie, Xin; Ji, Jun; Dong, Yanhan; Du, Yan; Tang, Wei; Zheng, Xiaobo; Wang, Ping; Zhang, Zhengguang

    2014-11-01

    The rice blast fungus Magnaporthe oryzae encodes eight regulators of G-protein (GTP-binding protein) signaling (RGS) proteins MoRgs1-MoRgs8 that orchestrate the growth, asexual/sexual production, appressorium differentiation, and pathogenicity. To address the mechanisms by which MoRgs proteins function, we conducted a 2DE proteome study and identified 82 differentially expressed proteins by comparing five ∆Morgs mutants with wild-type Guy11 strain. We found that the abundances of eight amino acid (AA) biosynthesis or degradation associated proteins were markedly altered in five ∆Morgs mutants, indicating one of the main collective roles for the MoRgs proteins is to influence AA metabolism. We showed that MoRgs proteins have distinct roles in AA metabolism and nutrient responses from growth assays. In addition, we characterized MoLys20 (Lys is lysine), a homocitrate synthase, whose abundance was significantly decreased in the ∆Morgs mutants. The ∆Molys20 mutant is auxotrophic for lys and exogenous lys could partially rescue its auxotrophic defects. Deletion of MoLYS20 resulted in defects in conidiation and infection, as well as pathogenicity on rice. Overall, our results indicate that one of the critical roles for MoRgs proteins is to regulate AA metabolism, and that MoLys20 may be directly or indirectly regulated by MoRgs and participated in lys biosynthesis, thereby affecting fungal development and pathogenicity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. 21 CFR 888.3030 - Single/multiple component metallic bone fixation appliances and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Single/multiple component metallic bone fixation....3030 Single/multiple component metallic bone fixation appliances and accessories. (a) Identification. Single/multiple component metallic bone fixation appliances and accessories are devices intended to be...

  2. 21 CFR 888.3030 - Single/multiple component metallic bone fixation appliances and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Single/multiple component metallic bone fixation....3030 Single/multiple component metallic bone fixation appliances and accessories. (a) Identification. Single/multiple component metallic bone fixation appliances and accessories are devices intended to be...

  3. 21 CFR 888.3030 - Single/multiple component metallic bone fixation appliances and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Single/multiple component metallic bone fixation....3030 Single/multiple component metallic bone fixation appliances and accessories. (a) Identification. Single/multiple component metallic bone fixation appliances and accessories are devices intended to be...

  4. 21 CFR 888.3030 - Single/multiple component metallic bone fixation appliances and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Single/multiple component metallic bone fixation....3030 Single/multiple component metallic bone fixation appliances and accessories. (a) Identification. Single/multiple component metallic bone fixation appliances and accessories are devices intended to be...

  5. 21 CFR 888.3030 - Single/multiple component metallic bone fixation appliances and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Single/multiple component metallic bone fixation....3030 Single/multiple component metallic bone fixation appliances and accessories. (a) Identification. Single/multiple component metallic bone fixation appliances and accessories are devices intended to be...

  6. In Vitro Reconstitution of Autophagosome-Lysosome Fusion.

    PubMed

    Diao, J; Li, L; Lai, Y; Zhong, Q

    2017-01-01

    SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) proteins are a highly regulated class of membrane proteins lying in the center of membrane fusion. In conjunction with accessory proteins, SNAREs drive efficient merger of two distinct lipid bilayers into one interconnected structure. This chapter describes our fluorescence resonance energy transfer (FRET)-based proteoliposome fusion assays for the roles of various SNARE proteins, accessory proteins, and effects of different lipid compositions on membrane fusion involved in autophagy. © 2017 Elsevier Inc. All rights reserved.

  7. Mechanism and Regulation of Protein Synthesis in Saccharomyces cerevisiae

    PubMed Central

    Dever, Thomas E.; Kinzy, Terri Goss; Pavitt, Graham D.

    2016-01-01

    In this review, we provide an overview of protein synthesis in the yeast Saccharomyces cerevisiae. The mechanism of protein synthesis is well conserved between yeast and other eukaryotes, and molecular genetic studies in budding yeast have provided critical insights into the fundamental process of translation as well as its regulation. The review focuses on the initiation and elongation phases of protein synthesis with descriptions of the roles of translation initiation and elongation factors that assist the ribosome in binding the messenger RNA (mRNA), selecting the start codon, and synthesizing the polypeptide. We also examine mechanisms of translational control highlighting the mRNA cap-binding proteins and the regulation of GCN4 and CPA1 mRNAs. PMID:27183566

  8. Successful catheter ablation of a left anterior accessory pathway from the non-coronary cusp of the aortic valve.

    PubMed

    Laranjo, Sérgio; Oliveira, Mário; Trigo, Conceição

    2015-08-01

    Left anterior accessory pathways are considered to be rare findings. Catheter ablation of accessory pathways in this location remains a challenging target, and few reports about successful ablation of these accessory pathways are available. We describe our experience regarding a case of a manifest left anterior accessory pathway ablation using radiofrequency energy at the junction of the left coronary cusp with the non-coronary cusp.

  9. Mammotome-Assisted Liposuction: A Novel Technique for Accessory Breasts.

    PubMed

    Tang, Xin

    2017-06-01

    Due to its minimally invasive and highly precise nature, the mammotome, a vacuum-assisted breast biopsy device, has proven effective for the treatment of benign breast lesions. Taking advantage of both liposuction and the mammotome, we utilized the mammotome device for the excision of accessory breasts. Between July 2010 and June 2014, 16 patients with accessory breasts received mammotome-assisted liposuction. After adipose was removed using this procedure, the mammotome system was used to excise the fibro-glandular tissue in accessory breasts under ultrasound monitoring. All patients were satisfied with their appearance after surgery. A single 5-mm incision, which was well hidden in the axillary skin folds and allowed for restoration, provided an aesthetically pleasing contour to the axilla. Mammotome-assisted liposuction is a new approach that can be used to excise both adipose and fibro-glandular breast tissue simultaneously with a minimal incision, and provides a favorable contour to the axilla. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  10. Accessory hepatic vein complicating extra-cardiac total cavopulmonary connection.

    PubMed

    Yoshii, Shinpei; Suzuki, Shoji; Osawa, Hiroshi; Hosaka, Shigeru; Honda, Yoshihiro; Abraham, Samuel J K; Tada, Yusuke; Sugiyama, Hisashi; Tan, Tetsushi; Kadono, Toshie; Hoshiai, Minako; Komai, Takayuki

    2002-04-01

    We encountered unexpected, severe hypoxia after the right heart bypass operation in a patient with isomerism. A 2-year-old girl with polysplenia had a complex cardiac anomaly consisting of a single atrium, single ventricle, pulmonary stenosis, absence of the right superior vena cava, hemiazygos continuation of the left inferior vena cava, and d-malposition of the great arteries. After a total cavopulmonary shunt, we performed an extra-cardiac total cavo-pulmonary connection with a 14 mm tube graft. The postoperative course was complicated by severe hypoxia. Angiography performed 20 days after the operation showed that contrast medium in the conduit poured into the hepatic vein, and through the intrahepatic communications, it passed into a left-sided accessory hepatic vein, which was connected directly to the left side of the aspect of the atrium. As the intrahepatic communication was adequate, we ligated the accessory hepatic vein within the pericardial cavity. The SpO2 returned to normal and no hepatic dysfunction was detected. We conclude that surgeons performing extra-cardiac total cavopulmonary connection need to pay closer attention to the possibility that an accessory hepatic vein might exist.

  11. Piezo Proteins: Regulators of Mechanosensation and Other Cellular Processes*

    PubMed Central

    Bagriantsev, Sviatoslav N.; Gracheva, Elena O.; Gallagher, Patrick G.

    2014-01-01

    Piezo proteins have recently been identified as ion channels mediating mechanosensory transduction in mammalian cells. Characterization of these channels has yielded important insights into mechanisms of somatosensation, as well as other mechano-associated biologic processes such as sensing of shear stress, particularly in the vasculature, and regulation of urine flow and bladder distention. Other roles for Piezo proteins have emerged, some unexpected, including participation in cellular development, volume regulation, cellular migration, proliferation, and elongation. Mutations in human Piezo proteins have been associated with a variety of disorders including hereditary xerocytosis and several syndromes with muscular contracture as a prominent feature. PMID:25305018

  12. Accessory carpal bone luxation in two gray wolves (Canis lupus).

    PubMed

    Keller, Dominique L; Ellison, Michelle; Clyde, Victoria L; Wallace, Roberta S

    2012-09-01

    Two sibling male castrated gray wolves (Canis lupus) developed acute onset right forelimb lameness, one at 8 and the other at 11 yr of age. In both cases, the right carpus was swollen, carpal hyperextension was notable, and the wolves exhibited significant intermittent lameness of the affected limb. Radiographs revealed right accessory carpal bone luxation in both cases, with type III fracture of the accessory carpal bone in one wolf. Although carpal bone luxation in domestic dogs is frequently treated surgically, conservative medical management resolved the lameness in both wolves with no further complications.

  13. Regulation of bone morphogenetic proteins in early embryonic development

    NASA Astrophysics Data System (ADS)

    Yamamoto, Yukiyo; Oelgeschläger, Michael

    2004-11-01

    Bone morphogenetic proteins (BMPs), a large subgroup of the TGF-β family of secreted growth factors, control fundamental events in early embryonic development, organogenesis and adult tissue homeostasis. The plethora of dose-dependent cellular processes regulated by BMP signalling demand a tight regulation of BMP activity. Over the last decade, a number of proteins have been identified that bind BMPs in the extracellular space and regulate the interaction of BMPs with their cognate receptors, including the secreted BMP antagonist Chordin. In the early vertebrate embryo, the localized secretion of BMP antagonists from the dorsal blastopore lip establishes a functional BMP signalling gradient that is required for the determination of the dorsoventral or back to belly body axis. In particular, inhibition of BMP activity is essential for the formation of neural tissue in the development of vertebrate and invertebrate embryos. Here we review recent studies that have provided new insight into the regulation of BMP signalling in the extracellular space. In particular, we discuss the recently identified Twisted gastrulation protein that modulates, in concert with metalloproteinases of the Tolloid family, the interaction of Chordin with BMP and a family of proteins that share structural similarities with Chordin in the respective BMP binding domains. In addition, genetic and functional studies in zebrafish and frog provide compelling evidence that the secreted protein Sizzled functionally interacts with the Chd BMP pathway, despite being expressed ventrally in the early gastrula-stage embryo. These intriguing discoveries may have important implications, not only for our current concept of early embryonic patterning, but also for the regulation of BMP activity at later developmental stages and tissue homeostasis in the adult.

  14. 21 CFR 872.6010 - Abrasive device and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6010 Abrasive device and accessories... crowns. The device is attached to a shank that is held by a handpiece. The device includes the abrasive...

  15. 21 CFR 872.6010 - Abrasive device and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6010 Abrasive device and accessories... crowns. The device is attached to a shank that is held by a handpiece. The device includes the abrasive...

  16. 21 CFR 872.6010 - Abrasive device and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6010 Abrasive device and accessories... crowns. The device is attached to a shank that is held by a handpiece. The device includes the abrasive...

  17. 21 CFR 872.6010 - Abrasive device and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6010 Abrasive device and accessories... crowns. The device is attached to a shank that is held by a handpiece. The device includes the abrasive...

  18. 21 CFR 872.6010 - Abrasive device and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6010 Abrasive device and accessories... crowns. The device is attached to a shank that is held by a handpiece. The device includes the abrasive...

  19. Abiotic regulation: a common way for proteins to modulate their functions.

    PubMed

    Zou, Zhi; Fu, Xinmiao

    2015-01-01

    Modulation of protein intrinsic activity in cells is generally carried out via a combination of four common ways, i.e., allosteric regulation, covalent modification, proteolytic cleavage and association of other regulatory proteins. Accumulated evidence indicate that changes of certain abiotic factors (e.g., temperature, pH, light and mechanical force) within or outside the cells directly influence protein structure and thus profoundly modulate the functions of a wide range of proteins, termed as abiotic regulatory proteins (e.g., heat shock factor, small heat shock protein, hemoglobin, zymogen, integrin, rhodopsin). Such abiotic regulation apparently differs from the four classic ways in perceiving and response to the signals. Importantly, it enables cells to directly and also immediately response to extracellular stimuli, thus facilitating the ability of organisms to resist against and adapt to the abiotic stress and thereby playing crucial roles in life evolution. Altogether, abiotic regulation may be considered as a common way for proteins to modulate their functions.

  20. Thick Filament Protein Network, Functions, and Disease Association.

    PubMed

    Wang, Li; Geist, Janelle; Grogan, Alyssa; Hu, Li-Yen R; Kontrogianni-Konstantopoulos, Aikaterini

    2018-03-13

    Sarcomeres consist of highly ordered arrays of thick myosin and thin actin filaments along with accessory proteins. Thick filaments occupy the center of sarcomeres where they partially overlap with thin filaments. The sliding of thick filaments past thin filaments is a highly regulated process that occurs in an ATP-dependent manner driving muscle contraction. In addition to myosin that makes up the backbone of the thick filament, four other proteins which are intimately bound to the thick filament, myosin binding protein-C, titin, myomesin, and obscurin play important structural and regulatory roles. Consistent with this, mutations in the respective genes have been associated with idiopathic and congenital forms of skeletal and cardiac myopathies. In this review, we aim to summarize our current knowledge on the molecular structure, subcellular localization, interacting partners, function, modulation via posttranslational modifications, and disease involvement of these five major proteins that comprise the thick filament of striated muscle cells. © 2018 American Physiological Society. Compr Physiol 8:631-709, 2018. Copyright © 2018 American Physiological Society. All rights reserved.

  1. Algal Accessory Pigment Detection Using AVIRIS Image-Derived Spectral Radiance Data

    NASA Technical Reports Server (NTRS)

    Richardson, Laurie L.; Ambrosia, Vincent G.

    1996-01-01

    Visual and derivative analyses of AVIRIS spectral data can be used to detect algal accessory pigments in aquatic communities. This capability extends the use of remote sensing for the study of aquatic ecosystems by allowing detection of taxonomically significant pigment signatures which yield information about the type of algae present. Such information allows remote sensing-based assessment of aquatic ecosystem health, as in the detection of nuisance blooms of cyanobacteria or toxic blooms of dinoflagellates. Remote sensing of aquatic systems has traditionally focused on quantification of chlorophyll a, a photoreactive (and light-harvesting) pigment which is common to all algae as well as cyanobacteria (bluegreen algae). Due to the ubiquitousness of this pigment within algae, chl a is routinely measured to estimate algal biomass both during ground-truthing and using various airborne or satellite based sensors, including AVIRIS. Within the remote sensing and aquatic sciences communities, ongoing research has been performed to detect algal accessory pigments for assessment of algal population composition. This research is based on the fact that many algal accessory pigments are taxonomically significant, and all are spectrally unique. Aquatic scientists have been refining pigment analysis techniques, primarily high performance liquid chromatography, or HPLC, to detect specific pigments as a time-saving alternative to individual algal cell identifications and counts. Remote sensing scientists are investigating the use of pigment signatures to construct pigment libraries analogous to mineral spectral libraries used in geological remote sensing applications. The accessory pigment approach has been used successfully in remote sensing using data from the Thematic Mapper, low-altitude, multiple channel scanners, field spectroradiometers and the AVIRIS hyperspectral scanner. Due to spectral and spatial resolution capabilities, AVIRIS is the sensor of choice for such

  2. Protein kinase A stimulates Kv7.1 surface expression by regulating Nedd4-2-dependent endocytic trafficking.

    PubMed

    Andersen, Martin N; Hefting, Louise L; Steffensen, Annette B; Schmitt, Nicole; Olesen, Søren-Peter; Olsen, Jesper V; Lundby, Alicia; Rasmussen, Hanne B

    2015-11-15

    The potassium channel Kv7.1 plays critical physiological roles in both heart and epithelial tissues. In heart, Kv7.1 and the accessory subunit KCNE1 forms the slowly activating delayed-rectifier potassium current current, which is enhanced by protein kinase A (PKA)-mediated phosphorylation. The observed current increase requires both phosphorylation of Kv7.1 and the presence of KCNE1. However, PKA also stimulates Kv7.1 currents in epithelial tissues, such as colon, where the channel does not coassemble with KCNE1. Here, we demonstrate that PKA activity significantly impacts the subcellular localization of Kv7.1 in Madin-Darby canine kidney cells. While PKA inhibition reduced the fraction of channels at the cell surface, PKA activation increased it. We show that PKA inhibition led to intracellular accumulation of Kv7.1 in late endosomes/lysosomes. By mass spectroscopy we identified eight phosphorylated residues on Kv7.1, however, none appeared to play a role in the observed response. Instead, we found that PKA acted by regulating endocytic trafficking involving the ubiquitin ligase Nedd4-2. We show that a Nedd4-2-resistant Kv7.1-mutant displayed significantly reduced intracellular accumulation upon PKA inhibition. Similar effects were observed upon siRNA knockdown of Nedd4-2. However, although Nedd4-2 is known to regulate Kv7.1 by ubiquitylation, biochemical analyses demonstrated that PKA did not influence the amount of Nedd4-2 bound to Kv7.1 or the ubiquitylation level of the channel. This suggests that PKA influences Nedd4-2-dependent Kv7.1 transport though a different molecular mechanism. In summary, we identify a novel mechanism whereby PKA can increase Kv7.1 current levels, namely by regulating Nedd4-2-dependent Kv7.1 transport. Copyright © 2015 the American Physiological Society.

  3. Protein kinase A stimulates Kv7.1 surface expression by regulating Nedd4-2-dependent endocytic trafficking

    PubMed Central

    Andersen, Martin N.; Hefting, Louise L.; Steffensen, Annette B.; Schmitt, Nicole; Olesen, Søren-Peter; Olsen, Jesper V.; Lundby, Alicia

    2015-01-01

    The potassium channel Kv7.1 plays critical physiological roles in both heart and epithelial tissues. In heart, Kv7.1 and the accessory subunit KCNE1 forms the slowly activating delayed-rectifier potassium current current, which is enhanced by protein kinase A (PKA)-mediated phosphorylation. The observed current increase requires both phosphorylation of Kv7.1 and the presence of KCNE1. However, PKA also stimulates Kv7.1 currents in epithelial tissues, such as colon, where the channel does not coassemble with KCNE1. Here, we demonstrate that PKA activity significantly impacts the subcellular localization of Kv7.1 in Madin-Darby canine kidney cells. While PKA inhibition reduced the fraction of channels at the cell surface, PKA activation increased it. We show that PKA inhibition led to intracellular accumulation of Kv7.1 in late endosomes/lysosomes. By mass spectroscopy we identified eight phosphorylated residues on Kv7.1, however, none appeared to play a role in the observed response. Instead, we found that PKA acted by regulating endocytic trafficking involving the ubiquitin ligase Nedd4-2. We show that a Nedd4-2-resistant Kv7.1-mutant displayed significantly reduced intracellular accumulation upon PKA inhibition. Similar effects were observed upon siRNA knockdown of Nedd4-2. However, although Nedd4-2 is known to regulate Kv7.1 by ubiquitylation, biochemical analyses demonstrated that PKA did not influence the amount of Nedd4-2 bound to Kv7.1 or the ubiquitylation level of the channel. This suggests that PKA influences Nedd4-2-dependent Kv7.1 transport though a different molecular mechanism. In summary, we identify a novel mechanism whereby PKA can increase Kv7.1 current levels, namely by regulating Nedd4-2-dependent Kv7.1 transport. PMID:26405101

  4. 49 CFR 390.17 - Additional equipment and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... equipment and accessories, not inconsistent with or prohibited by this subchapter, provided such equipment... are used. [53 FR 18052, May 19, 1988, as amended at 60 FR 38744, July 28, 1995. Redesignated at 65 FR...

  5. Fe-S Proteins that Regulate Gene Expression

    PubMed Central

    Mettert, Erin L.; Kiley, Patricia J.

    2014-01-01

    Iron-sulfur (Fe-S) cluster containing proteins that regulate gene expression are present in most organisms. The innate chemistry of their Fe-S cofactors makes these regulatory proteins ideal for sensing environmental signals, such as gases (e.g. O2 and NO), levels of Fe and Fe-S clusters, reactive oxygen species, and redox cycling compounds, to subsequently mediate an adaptive response. Here we review the recent findings that have provided invaluable insight into the mechanism and function of these highly significant Fe-S regulatory proteins. PMID:25450978

  6. Split luciferase complementation assay to detect regulated protein-protein interactions in rice protoplasts in a large-scale format

    PubMed Central

    2014-01-01

    Background The rice interactome, in which a network of protein-protein interactions has been elucidated in rice, is a useful resource to identify functional modules of rice signal transduction pathways. Protein-protein interactions occur in cells in two ways, constitutive and regulative. While a yeast-based high-throughput method has been widely used to identify the constitutive interactions, a method to detect the regulated interactions is rarely developed for a large-scale analysis. Results A split luciferase complementation assay was applied to detect the regulated interactions in rice. A transformation method of rice protoplasts in a 96-well plate was first established for a large-scale analysis. In addition, an antibody that specifically recognizes a carboxyl-terminal fragment of Renilla luciferase was newly developed. A pair of antibodies that recognize amino- and carboxyl- terminal fragments of Renilla luciferase, respectively, was then used to monitor quality and quantity of interacting recombinant-proteins accumulated in the cells. For a proof-of-concept, the method was applied to detect the gibberellin-dependent interaction between GIBBERELLIN INSENSITIVE DWARF1 and SLENDER RICE 1. Conclusions A method to detect regulated protein-protein interactions was developed towards establishment of the rice interactome. PMID:24987490

  7. Light-Inducible Gene Regulation with Engineered Zinc Finger Proteins

    PubMed Central

    Polstein, Lauren R.; Gersbach, Charles A.

    2014-01-01

    The coupling of light-inducible protein-protein interactions with gene regulation systems has enabled the control of gene expression with light. In particular, heterodimer protein pairs from plants can be used to engineer a gene regulation system in mammalian cells that is reversible, repeatable, tunable, controllable in a spatiotemporal manner, and targetable to any DNA sequence. This system, Light-Inducible Transcription using Engineered Zinc finger proteins (LITEZ), is based on the blue light-induced interaction of GIGANTEA and the LOV domain of FKF1 that drives the localization of a transcriptional activator to the DNA-binding site of a highly customizable engineered zinc finger protein. This chapter provides methods for modifying LITEZ to target new DNA sequences, engineering a programmable LED array to illuminate cell cultures, and using the modified LITEZ system to achieve spatiotemporal control of transgene expression in mammalian cells. PMID:24718797

  8. Gene Expression in Human Accessory Lacrimal Glands of Wolfring

    PubMed Central

    Ubels, John L.; Gipson, Ilene K.; Spurr-Michaud, Sandra J.; Tisdale, Ann S.; Van Dyken, Rachel E.; Hatton, Mark P.

    2012-01-01

    Purpose. The accessory lacrimal glands are assumed to contribute to the production of tear fluid, but little is known about their function. The goal of this study was to conduct an analysis of gene expression by glands of Wolfring that would provide a more complete picture of the function of these glands. Methods. Glands of Wolfring were isolated from frozen sections of human eyelids by laser microdissection. RNA was extracted from the cells and hybridized to gene expression arrays. The expression of several of the major genes was confirmed by immunohistochemistry. Results. Of the 24 most highly expressed genes, 9 were of direct relevance to lacrimal function. These included lysozyme, lactoferrin, tear lipocalin, and lacritin. The glands of Wolfring are enriched in genes related to protein synthesis, targeting, and secretion, and a large number of genes for proteins with antimicrobial activity were detected. Ion channels and transporters, carbonic anhydrase, and aquaporins were abundantly expressed. Genes for control of lacrimal function, including cholinergic, adrenergic, vasoactive intestinal polypeptide, purinergic, androgen, and prolactin receptors were also expressed in gland of Wolfring. Conclusions. The data suggest that the function of glands of Wolfring is similar to that of main lacrimal glands and are consistent with secretion electrolytes, fluid, and protein under nervous and hormonal control. Since these glands secrete directly onto the ocular surface, their location may allow rapid response to exogenous stimuli and makes them readily accessible to topical drugs. PMID:22956620

  9. Whey proteins in the regulation of food intake and satiety.

    PubMed

    Luhovyy, Bohdan L; Akhavan, Tina; Anderson, G Harvey

    2007-12-01

    Whey protein has potential as a functional food component to contribute to the regulation of body weight by providing satiety signals that affect both short-term and long-term food intake regulation. Because whey is an inexpensive source of high nutritional quality protein, the utilization of whey as a physiologically functional food ingredient for weight management is of current interest. At present, the role of individual whey proteins and peptides in contributing to food intake regulation has not been fully defined. However, Whey protein reduces short-term food intake relative to placebo, carbohydrate and other proteins. Whey protein affects satiation and satiety by the actions of: (1) whey protein fractions per se; (2) bioactive peptides; (3) amino-acids released after digestion; (4) combined action of whey protein and/or peptides and/or amino acids with other milk constituents. Whey ingestion activates many components of the food intake regulatory system. Whey protein is insulinotropic, and whey-born peptides affect the renin-angiotensin system. Therefore whey protein has potential as physiologically functional food component for persons with obesity and its co-morbidities (hypertension, type II diabetes, hyper- and dislipidemia). It remains unclear, however, if the favourable effects of whey on food intake, subjective satiety and intake regulatory mechanisms in humans are obtained from usual serving sizes of dairy products. The effects described have been observed in short-term experiments and when whey is consumed in much higher amounts.

  10. The nucleotide composition of microbial genomes indicates differential patterns of selection on core and accessory genomes.

    PubMed

    Bohlin, Jon; Eldholm, Vegard; Pettersson, John H O; Brynildsrud, Ola; Snipen, Lars

    2017-02-10

    The core genome consists of genes shared by the vast majority of a species and is therefore assumed to have been subjected to substantially stronger purifying selection than the more mobile elements of the genome, also known as the accessory genome. Here we examine intragenic base composition differences in core genomes and corresponding accessory genomes in 36 species, represented by the genomes of 731 bacterial strains, to assess the impact of selective forces on base composition in microbes. We also explore, in turn, how these results compare with findings for whole genome intragenic regions. We found that GC content in coding regions is significantly higher in core genomes than accessory genomes and whole genomes. Likewise, GC content variation within coding regions was significantly lower in core genomes than in accessory genomes and whole genomes. Relative entropy in coding regions, measured as the difference between observed and expected trinucleotide frequencies estimated from mononucleotide frequencies, was significantly higher in the core genomes than in accessory and whole genomes. Relative entropy was positively associated with coding region GC content within the accessory genomes, but not within the corresponding coding regions of core or whole genomes. The higher intragenic GC content and relative entropy, as well as the lower GC content variation, observed in the core genomes is most likely associated with selective constraints. It is unclear whether the positive association between GC content and relative entropy in the more mobile accessory genomes constitutes signatures of selection or selective neutral processes.

  11. Protein-protein interactions in the regulation of WRKY transcription factors.

    PubMed

    Chi, Yingjun; Yang, Yan; Zhou, Yuan; Zhou, Jie; Fan, Baofang; Yu, Jing-Quan; Chen, Zhixiang

    2013-03-01

    It has been almost 20 years since the first report of a WRKY transcription factor, SPF1, from sweet potato. Great progress has been made since then in establishing the diverse biological roles of WRKY transcription factors in plant growth, development, and responses to biotic and abiotic stress. Despite the functional diversity, almost all analyzed WRKY proteins recognize the TTGACC/T W-box sequences and, therefore, mechanisms other than mere recognition of the core W-box promoter elements are necessary to achieve the regulatory specificity of WRKY transcription factors. Research over the past several years has revealed that WRKY transcription factors physically interact with a wide range of proteins with roles in signaling, transcription, and chromatin remodeling. Studies of WRKY-interacting proteins have provided important insights into the regulation and mode of action of members of the important family of transcription factors. It has also emerged that the slightly varied WRKY domains and other protein motifs conserved within each of the seven WRKY subfamilies participate in protein-protein interactions and mediate complex functional interactions between WRKY proteins and between WRKY and other regulatory proteins in the modulation of important biological processes. In this review, we summarize studies of protein-protein interactions for WRKY transcription factors and discuss how the interacting partners contribute, at different levels, to the establishment of the complex regulatory and functional network of WRKY transcription factors.

  12. Small things considered: the small accessory subunits of RNA polymerase in Gram-positive bacteria

    PubMed Central

    Weiss, Andy; Shaw, Lindsey N.

    2015-01-01

    The DNA-dependent RNA polymerase core enzyme in Gram-positive bacteria consists of seven subunits. Whilst four of them (α2ββ′) are essential, three smaller subunits, δ, ε and ω (∼9–21.5 kDa), are considered accessory. Both δ and ω have been viewed as integral components of RNAP for several decades; however, ε has only recently been described. Functionally these three small subunits carry out a variety of tasks, imparting important, supportive effects on the transcriptional process of Gram-positive bacteria. While ω is thought to have a wide range of roles, reaching from maintaining structural integrity of RNAP to σ factor recruitment, the only suggested function for ε thus far is in protecting cells from phage infection. The third subunit, δ, has been shown to have distinct influences in maintaining transcriptional specificity, and thus has a key role in cellular fitness. Collectively, all three accessory subunits, although dispensable under laboratory conditions, are often thought to be crucial for proper RNAP function. Herein we provide an overview of the available literature on each subunit, summarizing landmark findings that have deepened our understanding of these proteins and their function, and outline future challenges in understanding the role of these small subunits in the transcriptional process. PMID:25878038

  13. Giant accessory breast: a rare occurrence reported, with a review of the literature.

    PubMed

    Hiremath, Bharati; Subramaniam, Narayana; Chandrashekhar, Nayan

    2015-11-05

    Polymastia, or the presence of supranumerary breasts, occurs in 2-6% of the female population, the spectrum of the disorder ranging between a small mole and a fully functional ectopic breast. They are often asymptomatic but require treatment when symptomatic or if they harbour malignancy. We present a case of a 41-year-old woman with an accessory breast in the left inframammary fold, which increased in size over the decade following her first pregnancy, to reach a size almost three times that of her right breast. Preoperative fine-needle aspiration and ultrasound was suggestive of accessory breast tissue, distinct from the left breast. Intraoperatively, a 14×10×8 cm accessory breast was found in the inframammary fold, distinct from the left breast and having an accessory nipple areola complex as well. A simple mastectomy was performed with trimming and rotation of the inframammary flap. The patient was happy with the cosmetic outcome. This article also reviews the literature and covers classification of polymastia, diagnostic complexities and challenges associated with surgery. 2015 BMJ Publishing Group Ltd.

  14. Giant accessory breast: a rare occurrence reported, with a review of the literature

    PubMed Central

    Hiremath, Bharati; Subramaniam, Narayana; Chandrashekhar, Nayan

    2015-01-01

    Polymastia, or the presence of supranumerary breasts, occurs in 2–6% of the female population, the spectrum of the disorder ranging between a small mole and a fully functional ectopic breast. They are often asymptomatic but require treatment when symptomatic or if they harbour malignancy. We present a case of a 41-year-old woman with an accessory breast in the left inframammary fold, which increased in size over the decade following her first pregnancy, to reach a size almost three times that of her right breast. Preoperative fine-needle aspiration and ultrasound was suggestive of accessory breast tissue, distinct from the left breast. Intraoperatively, a 14×10×8 cm accessory breast was found in the inframammary fold, distinct from the left breast and having an accessory nipple areola complex as well. A simple mastectomy was performed with trimming and rotation of the inframammary flap. The patient was happy with the cosmetic outcome. This article also reviews the literature and covers classification of polymastia, diagnostic complexities and challenges associated with surgery. PMID:26542818

  15. 21 CFR 876.4300 - Endoscopic electrosurgical unit and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... accessories is a device used to perform electrosurgical procedures through an endoscope. This generic type of device includes the electrosurgical generator, patient plate, electric biopsy forceps, electrode...

  16. A Novel GLP1 Receptor Interacting Protein ATP6ap2 Regulates Insulin Secretion in Pancreatic Beta Cells*

    PubMed Central

    Dai, Feihan F.; Bhattacharjee, Alpana; Liu, Ying; Batchuluun, Battsetseg; Zhang, Ming; Wang, Xinye Serena; Huang, Xinyi; Luu, Lemieux; Zhu, Dan; Gaisano, Herbert; Wheeler, Michael B.

    2015-01-01

    GLP1 activates its receptor, GLP1R, to enhance insulin secretion. The activation and transduction of GLP1R requires complex interactions with a host of accessory proteins, most of which remain largely unknown. In this study, we used membrane-based split ubiquitin yeast two-hybrid assays to identify novel GLP1R interactors in both mouse and human islets. Among these, ATP6ap2 (ATPase H+-transporting lysosomal accessory protein 2) was identified in both mouse and human islet screens. ATP6ap2 was shown to be abundant in islets including both alpha and beta cells. When GLP1R and ATP6ap2 were co-expressed in beta cells, GLP1R was shown to directly interact with ATP6ap2, as assessed by co-immunoprecipitation. In INS-1 cells, overexpression of ATP6ap2 did not affect insulin secretion; however, siRNA knockdown decreased both glucose-stimulated and GLP1-induced insulin secretion. Decreases in GLP1-induced insulin secretion were accompanied by attenuated GLP1 stimulated cAMP accumulation. Because ATP6ap2 is a subunit required for V-ATPase assembly of insulin granules, it has been reported to be involved in granule acidification. In accordance with this, we observed impaired insulin granule acidification upon ATP6ap2 knockdown but paradoxically increased proinsulin secretion. Importantly, as a GLP1R interactor, ATP6ap2 was required for GLP1-induced Ca2+ influx, in part explaining decreased insulin secretion in ATP6ap2 knockdown cells. Taken together, our findings identify a group of proteins that interact with the GLP1R. We further show that one interactor, ATP6ap2, plays a novel dual role in beta cells, modulating both GLP1R signaling and insulin processing to affect insulin secretion. PMID:26272612

  17. A-Kinase Anchoring Proteins That Regulate Cardiac Remodeling

    PubMed Central

    Carnegie, Graeme K.; Burmeister, Brian T.

    2012-01-01

    In response to injury or stress, the adult heart undergoes maladaptive changes, collectively defined as pathological cardiac remodeling. Here, we focus on the role of A-kinase anchoring proteins (AKAPs) in 3 main areas associated with cardiac remodeling and the progression of heart failure: excitation–contraction coupling, sarcomeric regulation, and induction of pathological hypertrophy. AKAPs are a diverse family of scaffold proteins that form multi-protein complexes, integrating cAMP signaling with protein kinases, phosphatases, and other effector proteins. Many AKAPs have been characterized in the heart, where they play a critical role in modulating cardiac function. PMID:22075671

  18. LDL receptor-related protein 1 regulates the abundance of diverse cell-signaling proteins in the plasma membrane proteome.

    PubMed

    Gaultier, Alban; Simon, Gabriel; Niessen, Sherry; Dix, Melissa; Takimoto, Shinako; Cravatt, Benjamin F; Gonias, Steven L

    2010-12-03

    LDL receptor-related protein 1 (LRP1) is an endocytic receptor, reported to regulate the abundance of other receptors in the plasma membrane, including uPAR and tissue factor. The goal of this study was to identify novel plasma membrane proteins, involved in cell-signaling, that are regulated by LRP1. Membrane protein ectodomains were prepared from RAW 264.7 cells in which LRP1 was silenced and control cells using protease K. Peptides were identified by LC-MS/MS. By analysis of spectral counts, 31 transmembrane and secreted proteins were regulated in abundance at least 2-fold when LRP1 was silenced. Validation studies confirmed that semaphorin4D (Sema4D), plexin domain-containing protein-1 (Plxdc1), and neuropilin-1 were more abundant in the membranes of LRP1 gene-silenced cells. Regulation of Plxdc1 by LRP1 was confirmed in CHO cells, as a second model system. Plxdc1 coimmunoprecipitated with LRP1 from extracts of RAW 264.7 cells and mouse liver. Although Sema4D did not coimmunoprecipitate with LRP1, the cell-surface level of Sema4D was increased by RAP, which binds to LRP1 and inhibits binding of other ligands. These studies identify Plxdc1, Sema4D, and neuropilin-1 as novel LRP1-regulated cell-signaling proteins. Overall, LRP1 emerges as a generalized regulator of the plasma membrane proteome.

  19. MicroRNA regulation of F-box proteins and its role in cancer.

    PubMed

    Wu, Zhao-Hui; Pfeffer, Lawrence M

    2016-02-01

    MicroRNAs (miRNAs) are small endogenous non-coding RNAs, which play critical roles in cancer development by suppressing gene expression at the post-transcriptional level. In general, oncogenic miRNAs are upregulated in cancer, while miRNAs that act as tumor suppressors are downregulated, leading to decreased expression of tumor suppressors and upregulated oncogene expression, respectively. F-box proteins function as the substrate-recognition components of the SKP1-CUL1-F-box (SCF)-ubiquitin ligase complex for the degradation of their protein targets by the ubiquitin-proteasome system. Therefore F-box proteins and miRNAs both negatively regulate target gene expression post-transcriptionally. Since each miRNA is capable of fine-tuning the expression of multiple target genes, multiple F-box proteins may be suppressed by the same miRNA. Meanwhile, one F-box proteins could be regulated by several miRNAs in different cancer types. In this review, we will focus on miRNA-mediated downregulation of various F-box proteins, the resulting stabilization of F-box protein substrates and the impact of these processes on human malignancies. We provide insight into how the miRNA: F-box protein axis may regulate cancer progression and metastasis. We also consider the broader role of F-box proteins in the regulation of pathways that are independent of the ubiquitin ligase complex and how that impacts on oncogenesis. The area of miRNAs and the F-box proteins that they regulate in cancer is an emerging field and will inform new strategies in cancer treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Indispensable roles of mammalian Cbl family proteins as negative regulators of protein tyrosine kinase signaling

    PubMed Central

    Band, Vimla

    2011-01-01

    All higher eukaryotes utilize protein tyrosine kinases (PTKs) as molecular switches to control a variety of cellular signals. Notably, many PTKs have been identified as proto-oncogenes whose aberrant expression, mutations or co-option by pathogens can lead to human malignancies. Thus, it is obvious that PTK functions must be precisely regulated in order to maintain homeostasis of an organism. Investigations over the past fifteen years have revealed that members of the Cbl family proteins can serve as negative regulators of PTK signaling, and biochemical and cell biological studies have unraveled the mechanistic basis of this regulation. Yet, it is only recently that the field has begun to appreciate the real significance of this novel regulatory apparatus in shaping PTK-mediated signaling in organismic contexts and in human diseases. Here, we discuss recent progress in murine models that are beginning to provide insights into the critical roles of Cbl proteins in physiological pathways, with important implications in understanding how aberrations of Cbl proteins contribute to oncogenesis. PMID:21655429

  1. The scolopidial accessory organs and Nebenorgans in orthopteroid insects: Comparative neuroanatomy, mechanosensory function, and evolutionary origin.

    PubMed

    Strauß, Johannes

    2017-11-01

    Scolopidial sensilla in insects often form large sensory organs involved in proprioception or exteroception. Here the knowledge on Nebenorgans and accessory organs, two organs consisting of scolopidial sensory cells, is summarised. These organs are present in some insects which are model organisms for the physiology of mechanosensory systems (cockroaches and tettigoniids). Recent comparative studies documented the accessory organ in several taxa of Orthoptera (including tettigoniids, cave crickets, Jerusalem crickets) and the Nebenorgan in related insects (Mantophasmatodea). The accessory organ or Nebenorgan is usually a small organ of 8-15 sensilla located in the posterior leg tibia of all leg pairs. The physiological properties of the accessory organs and Nebenorgans are so far largely unknown. Taking together neuroanatomical and electrophysiological data from disparate taxa, there is considerable evidence that the accessory organ and Nebenorgan are vibrosensitive. They thus complement the larger vibrosensitive subgenual organ in the tibia. This review summarises the comparative studies of these sensory organs, in particular the arguments and criteria for the homology of the accessory organ and Nebenorgan among orthopteroid insects. Different scenarios of repeated evolutionary origins or losses of these sensory organs are discussed. Neuroanatomy allows to distinguish individual sensory organs for analysis of sensory physiology, and to infer scenarios of sensory evolution. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Accessories modifying based on plastic waste of shampoo bottle as home economic product

    NASA Astrophysics Data System (ADS)

    Setyowati, Erna; Sukesi, Siti

    2018-03-01

    Plastic is a waste that can not decompose by the soil and if its left without a good handling can pollute the environment. Plastic waste needs processing by the recycle bottles principle. Shampoo bottle is one of plastic waste with high density polyethylene type (HDPE). One of the innovation to recycling shampoo bottles waste into the new products whichbeneficially and aestheticallyform by engineered the buns accesories. Accessories are one of the tools used by most women, in the form of trinkets or ornaments which ajusted to the trend to beautify the look. Accessories from shampoo bottle waste can be obtained from household waste, beauty salon and the beauty program study by inculcating human beings' behavior by transforming waste into blessing while also increasing family income. Technique of making its by compiling through improvement of panelist team. The goal of this research is to engineering theaccessories based on shampoo bottle waste as home economics. The method are using experiment, observation and documentation, analysis using descriptive. The results obtained from the overall sensory test averaged at 93%, while the favored test averaged at 85.5%. The product can be ordered according to the desired design, but it takes a long time. Therefore accessories engineering from shampoo bottles waste-based can be used as home economics. The production of shampoo bottles waste-based accessories should improved its quality and quantity, to be marketed through the community, by the cooperation with accessories and bun craftsmen.

  3. Minireview: Role of Intracellular Scaffolding Proteins in the Regulation of Endocrine G Protein-Coupled Receptor Signaling

    PubMed Central

    Walther, Cornelia

    2015-01-01

    The majority of hormones stimulates and mediates their signal transduction via G protein-coupled receptors (GPCRs). The signal is transmitted into the cell due to the association of the GPCRs with heterotrimeric G proteins, which in turn activates an extensive array of signaling pathways to regulate cell physiology. However, GPCRs also function as scaffolds for the recruitment of a variety of cytoplasmic protein-interacting proteins that bind to both the intracellular face and protein interaction motifs encoded by GPCRs. The structural scaffolding of these proteins allows GPCRs to recruit large functional complexes that serve to modulate both G protein-dependent and -independent cellular signaling pathways and modulate GPCR intracellular trafficking. This review focuses on GPCR interacting PSD95-disc large-zona occludens domain containing scaffolds in the regulation of endocrine receptor signaling as well as their potential role as therapeutic targets for the treatment of endocrinopathies. PMID:25942107

  4. 21 CFR 884.1690 - Hysteroscope and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... specialized instrument or device delivery system; do not have adapters, connectors, channels, or do not have... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Hysteroscope and accessories. 884.1690 Section 884.1690 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

  5. 21 CFR 884.1690 - Hysteroscope and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... specialized instrument or device delivery system; do not have adapters, connectors, channels, or do not have... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Hysteroscope and accessories. 884.1690 Section 884.1690 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

  6. 21 CFR 884.1690 - Hysteroscope and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... specialized instrument or device delivery system; do not have adapters, connectors, channels, or do not have... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Hysteroscope and accessories. 884.1690 Section 884.1690 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

  7. 21 CFR 884.1690 - Hysteroscope and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... specialized instrument or device delivery system; do not have adapters, connectors, channels, or do not have... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hysteroscope and accessories. 884.1690 Section 884.1690 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

  8. 21 CFR 884.1690 - Hysteroscope and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... specialized instrument or device delivery system; do not have adapters, connectors, channels, or do not have... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Hysteroscope and accessories. 884.1690 Section 884.1690 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

  9. 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

  10. Piezo proteins: regulators of mechanosensation and other cellular processes.

    PubMed

    Bagriantsev, Sviatoslav N; Gracheva, Elena O; Gallagher, Patrick G

    2014-11-14

    Piezo proteins have recently been identified as ion channels mediating mechanosensory transduction in mammalian cells. Characterization of these channels has yielded important insights into mechanisms of somatosensation, as well as other mechano-associated biologic processes such as sensing of shear stress, particularly in the vasculature, and regulation of urine flow and bladder distention. Other roles for Piezo proteins have emerged, some unexpected, including participation in cellular development, volume regulation, cellular migration, proliferation, and elongation. Mutations in human Piezo proteins have been associated with a variety of disorders including hereditary xerocytosis and several syndromes with muscular contracture as a prominent feature. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Progress in the clinical imaging research of bone diseases on ankle and foot sesamoid bones and accessory ossicles

    PubMed Central

    Li, Xiaozhong; Shi, Lenian; Liu, Taiyun; Wang, Lin

    2012-01-01

    Summary Sesamoid bones and accessory ossicles are research focuses of foot and ankle surgery. Pains of the foot and ankle are related to sesamoid bones and accessory ossicles. The specific anatomical and functional relationship of sesamoid bones and accessory ossicles can cause such bone diseases as the dislocation of sesamoid bones and accessory bones, infection, inflammation and necrosis of sesamoid bones, cartilage softening, tenosynovitis of sesamoid bones and the sesamoid bone syndrome. However, these bone diseases are often misdiagnosed or mistreated. In patients with trauma history, relevant diseases of sesamoid bones and accessory ossicles as above mentioned are highly probable to be misdiagnosed as avulsion fractures. In such cases, radiographic findings may provide a basis for clinical diagnosis. PMID:25343083

  12. Regulation of neurite morphogenesis by interaction between R7 regulator of G protein signaling complexes and G protein subunit Gα13.

    PubMed

    Scherer, Stephanie L; Cain, Matthew D; Kanai, Stanley M; Kaltenbronn, Kevin M; Blumer, Kendall J

    2017-06-16

    The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gβ 5 and R7-RGS-binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of G i/o α-subunits, several neurological phenotypes of R7-RGS knock-out mice are not readily explained by dysregulated G i/o signaling. Accordingly, we used tandem affinity purification and LC-MS/MS to search for novel proteins that interact with R7-RGS heterotrimers in the mouse brain. Among several proteins detected, we focused on Gα 13 because it had not been linked to R7-RGS complexes before. Split-luciferase complementation assays indicated that Gα 13 in its active or inactive state interacts with R7-RGS heterotrimers containing any R7-RGS isoform. LARG (leukemia-associated Rho guanine nucleotide exchange factor (GEF)), PDZ-RhoGEF, and p115RhoGEF augmented interaction between activated Gα 13 and R7-RGS heterotrimers, indicating that these effector RhoGEFs can engage Gα 13 ·R7-RGS complexes. Because Gα 13 /R7-RGS interaction required R7BP, we analyzed phenotypes of neuronal cell lines expressing RGS7 and Gβ 5 with or without R7BP. We found that neurite retraction evoked by Gα 12/13 -dependent lysophosphatidic acid receptors was augmented in R7BP-expressing cells. R7BP expression blunted neurite formation evoked by serum starvation by signaling mechanisms involving Gα 12/13 but not Gα i/o These findings provide the first evidence that R7-RGS heterotrimers interact with Gα 13 to augment signaling pathways that regulate neurite morphogenesis. This mechanism expands the diversity of functions whereby R7-RGS complexes regulate critical aspects of nervous system development and function. © 2017 by

  13. N-MYC down-regulated-like proteins regulate meristem initiation by modulating auxin transport and MAX2 expression.

    PubMed

    Mudgil, Yashwanti; Ghawana, Sanjay; Jones, Alan M

    2013-01-01

    N-MYC down-regulated-like (NDL) proteins interact with the Gβ subunit (AGB1) of the heterotrimeric G protein complex and play an important role in AGB1-dependent regulation of lateral root formation by affecting root auxin transport, auxin gradients and the steady-state levels of mRNA encoding the PIN-FORMED 2 and AUXIN 1 auxin transport facilitators. Auxin transport in aerial tissue follows different paths and utilizes different transporters than in roots; therefore, in the present study, we analyzed whether NDL proteins play an important role in AGB1-dependent, auxin-mediated meristem development. Expression levels of NDL gene family members need to be tightly regulated, and altered expression (both over-expression and down-regulation) confers ectopic growth. Over-expression of NDL1 disrupts vegetative and reproductive organ development. Reduced expression of the NDL gene family members results in asymmetric leaf emergence, twinning of rosette leaves, defects in leaf formation, and abnormal silique distribution. Reduced expression of the NDL genes in the agb1-2 (null allele) mutant rescues some of the abnormal phenotypes, such as silique morphology, silique distribution, and peduncle angle, suggesting that proper levels of NDL proteins are maintained by AGB1. We found that all of these abnormal aerial phenotypes due to altered NDL expression were associated with increases in basipetal auxin transport, altered auxin maxima and altered MAX2 expression within the inflorescence stem. NDL proteins, together with AGB1, act as positive regulators of meristem initiation and branching. AGB1 and NDL1 positively regulate basipetal inflorescence auxin transport and modulate MAX2 expression in shoots, which in turn regulates organ and lateral meristem formation by the establishment and maintenance of auxin gradients.

  14. N-MYC DOWN-REGULATED-LIKE Proteins Regulate Meristem Initiation by Modulating Auxin Transport and MAX2 Expression

    PubMed Central

    Mudgil, Yashwanti; Ghawana, Sanjay; Jones, Alan M.

    2013-01-01

    Background N-MYC DOWN-REGULATED-LIKE (NDL) proteins interact with the Gβ subunit (AGB1) of the heterotrimeric G protein complex and play an important role in AGB1-dependent regulation of lateral root formation by affecting root auxin transport, auxin gradients and the steady-state levels of mRNA encoding the PIN-FORMED 2 and AUXIN 1 auxin transport facilitators. Auxin transport in aerial tissue follows different paths and utilizes different transporters than in roots; therefore, in the present study, we analyzed whether NDL proteins play an important role in AGB1-dependent, auxin-mediated meristem development. Methodology/Principal Findings Expression levels of NDL gene family members need to be tightly regulated, and altered expression (both over-expression and down-regulation) confers ectopic growth. Over-expression of NDL1 disrupts vegetative and reproductive organ development. Reduced expression of the NDL gene family members results in asymmetric leaf emergence, twinning of rosette leaves, defects in leaf formation, and abnormal silique distribution. Reduced expression of the NDL genes in the agb1-2 (null allele) mutant rescues some of the abnormal phenotypes, such as silique morphology, silique distribution, and peduncle angle, suggesting that proper levels of NDL proteins are maintained by AGB1. We found that all of these abnormal aerial phenotypes due to altered NDL expression were associated with increases in basipetal auxin transport, altered auxin maxima and altered MAX2 expression within the inflorescence stem. Conclusion/Significance NDL proteins, together with AGB1, act as positive regulators of meristem initiation and branching. AGB1 and NDL1 positively regulate basipetal inflorescence auxin transport and modulate MAX2 expression in shoots, which in turn regulates organ and lateral meristem formation by the establishment and maintenance of auxin gradients. PMID:24223735

  15. A role for AT1 receptor-associated proteins in blood pressure regulation.

    PubMed

    Castrop, Hayo

    2015-04-01

    The renin angiotensin-system is one of the most important humoral regulators of blood pressure. The recently discovered angiotensin receptor-associated proteins serve as local modulators of the renin angiotensin-system. These proteins interact with the AT1 receptor in a tissue-specific manner and regulate the sensitivity of the target cell for angiotensin II. The predominant effect of the AT1 receptor-associated proteins on angiotensin II-induced signaling is the modulation of the surface expression of the AT1 receptor. This review provides an overview of our current knowledge with respect to the relevance of AT1 receptor-associated proteins for blood pressure regulation. Two aspects of blood pressure regulation will be discussed in detail: angiotensin II-dependent volume homoeostasis and vascular resistance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. The RNA binding protein CsrA controls c-di-GMP metabolism by directly regulating the expression of GGDEF proteins

    PubMed Central

    Jonas, Kristina; Edwards, Adrianne N.; Simm, Roger; Romeo, Tony; Römling, Ute; Melefors, Öjar

    2009-01-01

    Summary The carbon storage regulator CsrA is an RNA binding protein that controls carbon metabolism, biofilm formation and motility in various eubacteria. Nevertheless, in Escherichia coli only five target mRNAs have been shown to be directly regulated by CsrA at the post-transcriptional level. Here we identified two new direct targets for CsrA, ycdT and ydeH, both of which encode proteins with GGDEF domains. A csrA mutation caused mRNA levels of ycdT and ydeH to increase more than 10-fold. RNA mobility shift assays confirmed the direct and specific binding of CsrA to the mRNA leaders of ydeH and ycdT. Overexpression of ycdT and ydeH resulted in a more than 20-fold increase in the cellular concentration of the second messenger c-di-GMP, implying that both proteins possess diguanylate cyclase activity. Phenotypic characterization revealed that both proteins are involved in the regulation of motility in a c-di-GMP dependent manner. CsrA was also found to regulate the expression of five additional GGDEF/EAL proteins and a csrA mutation led to modestly increased cellular levels of c-di-GMP. All together, these data demonstrate a global role for CsrA in the regulation of c-di-GMP metabolism by regulating the expression of GGDEF proteins at the post-transcriptional level. PMID:18713317

  17. 77 FR 22802 - Certain Handbags, Luggage, Accessories, and Packaging Thereof; Determination Not To Review an...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-17

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-754] Certain Handbags, Luggage, Accessories, and Packaging Thereof; Determination Not To Review an Initial Determination Granting Complainant... importation of certain handbags, luggage, accessories, and packaging thereof by reason of infringement of U.S...

  18. Three-dimensional finite element analysis on canine teeth distalization by different accessories of bracket-free invisible orthodontics technology

    NASA Astrophysics Data System (ADS)

    Xu, Nuo; Lei, Xue; Yang, Xiaoli; Li, Xinhui; Ge, Zhenlin

    2018-04-01

    Objective: to compare canine tooth stress distribution condition during maxillary canine tooth distalization by different accessories of bracket-free invisible orthodontics technology after removal of maxillary first premolar, and provide basis for clinical design of invisible orthodontics technology. Method: CBCT scanning image of a patient with individual normal occlusion was adopted, Mimics, Geomagic and ProlE software were used for establishing three-dimensional models of maxilla, maxillary dentition, parodontium, invisible orthodontics appliance and accessories, ANSYS WORKBENCH was utilized as finite element analysis tools for analyzing stress distribution and movement pattern of canine tooth and parodontium when canine tooth was equipped with power arm and vertical rectangle accessory. Meanwhile, canine tooth none-accessory design group was regarded as a control. Result: teeth had even bistal surface stress distribution in the power arm group; stress was concentrated on distal tooth neck, and the stress was gradually deviated to mesial-labial side and distal lingual side in vertical rectangle group and none-accessory group. Conclusion: teeth tend to move as a whole in the Power arm group, vertical rectangle group has lower tooth gradient compared with the none-accessory group, teeth are inclined for movement in the none-accessory group, and canine teeth tend to rotate to the distal lingual side.

  19. Thermomechanical milling of accessory lithics in volcanic conduits

    NASA Astrophysics Data System (ADS)

    Campbell, Michelle E.; Russell, James K.; Porritt, Lucy A.

    2013-09-01

    Accessory lithic clasts recovered from pyroclastic deposits commonly result from the failure of conduit wall rocks, and represent an underutilized resource for constraining conduit processes during explosive volcanic eruptions. The morphological features of lithic clasts provide distinctive 'textural fingerprints' of processes that have reshaped them during transport in the conduit. Here, we present the first study focused on accessory lithic clast morphology and show how the shapes and surfaces of these accessory pyroclasts can inform on conduit processes. We use two main types of accessory lithic clasts from pyroclastic fallout deposits of the 2360 B.P. subplinian eruption of Mount Meager, British Columbia, as a case study: (i) rough and subangular dacite clasts, and (ii) variably rounded and smoothed monzogranite clasts. The quantitative morphological data collected on these lithics include: mass, volume, density, 2-D image analysis of convexity (C), and 3-D laser scans for sphericity (Ψ) and smoothness (S). Shaping and comminution (i.e. milling) of clasts within the conduit are ascribed to three processes: (1) disruptive fragmentation due to high-energy impacts between clasts or between clasts and conduit walls, (2) ash-blasting of clasts suspended within the volcanic flux, and (3) thermal effects. We use a simplified conduit eruption model to predict ash-blasting velocities and lithic residence times as a function of clast size and source depth, thereby constraining the lithic milling processes. The extent of shape and surface modification (i.e. rounding and honing) is directly proportional to clast residence times within the conduit prior to evacuation. We postulate that the shallow-seated dacite clasts remain subangular and rough due to short (<2 min) residence times, whereas monzogranite clasts are much more rounded and smoothed due to deeper source depths and consequently longer residence times (up to ˜1 h). Larger monzogranite clasts are smoother than

  20. Rad51 is an accessory factor for Dmc1-mediated joint molecule formation during meiosis.

    PubMed

    Cloud, Veronica; Chan, Yuen-Ling; Grubb, Jennifer; Budke, Brian; Bishop, Douglas K

    2012-09-07

    Meiotic recombination in budding yeast requires two RecA-related proteins, Rad51 and Dmc1, both of which form filaments on DNA capable of directing homology search and catalyzing formation of homologous joint molecules (JMs) and strand exchange. With use of a separation-of-function mutant form of Rad51 that retains filament-forming but not JM-forming activity, we show that the JM activity of Rad51 is fully dispensable for meiotic recombination. The corresponding mutation in Dmc1 causes a profound recombination defect, demonstrating Dmc1's JM activity alone is responsible for meiotic recombination. We further provide biochemical evidence that Rad51 acts with Mei5-Sae3 as a Dmc1 accessory factor. Thus, Rad51 is a multifunctional protein that catalyzes recombination directly in mitosis and indirectly, via Dmc1, during meiosis.

  1. Regulation of gene transcription by Polycomb proteins

    PubMed Central

    Aranda, Sergi; Mas, Gloria; Di Croce, Luciano

    2015-01-01

    The Polycomb group (PcG) of proteins defines a subset of factors that physically associate and function to maintain the positional identity of cells from the embryo to adult stages. PcG has long been considered a paradigmatic model for epigenetic maintenance of gene transcription programs. Despite intensive research efforts to unveil the molecular mechanisms of action of PcG proteins, several fundamental questions remain unresolved: How many different PcG complexes exist in mammalian cells? How are PcG complexes targeted to specific loci? How does PcG regulate transcription? In this review, we discuss the diversity of PcG complexes in mammalian cells, examine newly identified modes of recruitment to chromatin, and highlight the latest insights into the molecular mechanisms underlying the function of PcGs in transcription regulation and three-dimensional chromatin conformation. PMID:26665172

  2. Acute myotube protein synthesis regulation by IL-6-related cytokines.

    PubMed

    Gao, Song; Durstine, J Larry; Koh, Ho-Jin; Carver, Wayne E; Frizzell, Norma; Carson, James A

    2017-11-01

    IL-6 and leukemia inhibitory factor (LIF), members of the IL-6 family of cytokines, play recognized paradoxical roles in skeletal muscle mass regulation, being associated with both growth and atrophy. Overload or muscle contractions can induce a transient increase in muscle IL-6 and LIF expression, which has a regulatory role in muscle hypertrophy. However, the cellular mechanisms involved in this regulation have not been completely identified. The induction of mammalian target of rapamycin complex 1 (mTORC1)-dependent myofiber protein synthesis is an established regulator of muscle hypertrophy, but the involvement of the IL-6 family of cytokines in this process is poorly understood. Therefore, we investigated the acute effects of IL-6 and LIF administration on mTORC1 signaling and protein synthesis in C2C12 myotubes. The role of glycoprotein 130 (gp130) receptor and downstream signaling pathways, including phosphoinositide 3-kinase (PI3K)-Akt-mTORC1 and signal transducer and activator of transcription 3 (STAT3)-suppressor of cytokine signaling 3 (SOCS3), was investigated by administration of specific siRNA or pharmaceutical inhibitors. Acute administration of IL-6 and LIF induced protein synthesis, which was accompanied by STAT3 activation, Akt-mTORC1 activation, and increased SOCS3 expression. This induction of protein synthesis was blocked by both gp130 siRNA knockdown and Akt inhibition. Interestingly, STAT3 inhibition or Akt downstream mTORC1 signaling inhibition did not fully block the IL-6 or LIF induction of protein synthesis. SOCS3 siRNA knockdown increased basal protein synthesis and extended the duration of the protein synthesis induction by IL-6 and LIF. These results demonstrate that either IL-6 or LIF can activate gp130-Akt signaling axis, which induces protein synthesis via mTORC1-independent mechanisms in cultured myotubes. However, IL-6- or LIF-induced SOCS3 negatively regulates the activation of myotube protein synthesis. Copyright © 2017 the

  3. A-kinase anchoring proteins that regulate cardiac remodeling.

    PubMed

    Carnegie, Graeme K; Burmeister, Brian T

    2011-11-01

    In response to injury or stress, the adult heart undergoes maladaptive changes, collectively defined as pathological cardiac remodeling. Here, we focus on the role of A-kinase anchoring proteins (AKAPs) in 3 main areas associated with cardiac remodeling and the progression of heart failure: excitation-contraction coupling, sarcomeric regulation, and induction of pathological hypertrophy. AKAPs are a diverse family of scaffold proteins that form multiprotein complexes, integrating cAMP signaling with protein kinases, phosphatases, and other effector proteins. Many AKAPs have been characterized in the heart, where they play a critical role in modulating cardiac function.

  4. Hypothesis and Theory: Revisiting Views on the Co-evolution of the Melanocortin Receptors and the Accessory Proteins, MRAP1 and MRAP2.

    PubMed

    Dores, Robert M

    2016-01-01

    The evolution of the melanocortin receptors (MCRs) is closely associated with the evolution of the melanocortin-2 receptor accessory proteins (MRAPs). Recent annotation of the elephant shark genome project revealed the sequence of a putative MRAP1 ortholog. The presence of this sequence in the genome of a cartilaginous fish raises the possibility that the mrap1 and mrap2 genes in the genomes of gnathostome vertebrates were the result of the chordate 2R genome duplication event. The presence of a putative MRAP1 ortholog in a cartilaginous fish genome is perplexing. Recent studies on melanocortin-2 receptor (MC2R) in the genomes of the elephant shark and the Japanese stingray indicate that these MC2R orthologs can be functionally expressed in CHO cells without co-expression of an exogenous mrap1 cDNA. The novel ligand selectivity of these cartilaginous fish MC2R orthologs is discussed. Finally, the origin of the mc2r and mc5r genes is reevaluated. The distinctive primary sequence conservation of MC2R and MC5R is discussed in light of the physiological roles of these two MCR paralogs.

  5. Hypothesis and Theory: Revisiting Views on the Co-evolution of the Melanocortin Receptors and the Accessory Proteins, MRAP1 and MRAP2

    PubMed Central

    Dores, Robert M.

    2016-01-01

    The evolution of the melanocortin receptors (MCRs) is closely associated with the evolution of the melanocortin-2 receptor accessory proteins (MRAPs). Recent annotation of the elephant shark genome project revealed the sequence of a putative MRAP1 ortholog. The presence of this sequence in the genome of a cartilaginous fish raises the possibility that the mrap1 and mrap2 genes in the genomes of gnathostome vertebrates were the result of the chordate 2R genome duplication event. The presence of a putative MRAP1 ortholog in a cartilaginous fish genome is perplexing. Recent studies on melanocortin-2 receptor (MC2R) in the genomes of the elephant shark and the Japanese stingray indicate that these MC2R orthologs can be functionally expressed in CHO cells without co-expression of an exogenous mrap1 cDNA. The novel ligand selectivity of these cartilaginous fish MC2R orthologs is discussed. Finally, the origin of the mc2r and mc5r genes is reevaluated. The distinctive primary sequence conservation of MC2R and MC5R is discussed in light of the physiological roles of these two MCR paralogs. PMID:27445982

  6. The UbiK protein is an accessory factor necessary for bacterial ubiquinone (UQ) biosynthesis and forms a complex with the UQ biogenesis factor UbiJ.

    PubMed

    Loiseau, Laurent; Fyfe, Cameron; Aussel, Laurent; Hajj Chehade, Mahmoud; Hernández, Sara B; Faivre, Bruno; Hamdane, Djemel; Mellot-Draznieks, Caroline; Rascalou, Bérengère; Pelosi, Ludovic; Velours, Christophe; Cornu, David; Lombard, Murielle; Casadesús, Josep; Pierrel, Fabien; Fontecave, Marc; Barras, Frédéric

    2017-07-14

    Ubiquinone (UQ), also referred to as coenzyme Q, is a widespread lipophilic molecule in both prokaryotes and eukaryotes in which it primarily acts as an electron carrier. Eleven proteins are known to participate in UQ biosynthesis in Escherichia coli , and we recently demonstrated that UQ biosynthesis requires additional, nonenzymatic factors, some of which are still unknown. Here, we report on the identification of a bacterial gene, yqiC , which is required for efficient UQ biosynthesis, and which we have renamed ubiK Using several methods, we demonstrated that the UbiK protein forms a complex with the C-terminal part of UbiJ, another UQ biogenesis factor we previously identified. We found that both proteins are likely to contribute to global UQ biosynthesis rather than to a specific biosynthetic step, because both ubiK and ubiJ mutants accumulated octaprenylphenol, an early intermediate of the UQ biosynthetic pathway. Interestingly, we found that both proteins are dispensable for UQ biosynthesis under anaerobiosis, even though they were expressed in the absence of oxygen. We also provide evidence that the UbiK-UbiJ complex interacts with palmitoleic acid, a major lipid in E. coli Last, in Salmonella enterica , ubiK was required for proliferation in macrophages and virulence in mice. We conclude that although the role of the UbiK-UbiJ complex remains unknown, our results support the hypothesis that UbiK is an accessory factor of Ubi enzymes and facilitates UQ biosynthesis by acting as an assembly factor, a targeting factor, or both. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. 14-3-3 proteins regulate desmosomal adhesion via plakophilins.

    PubMed

    Rietscher, Katrin; Keil, René; Jordan, Annemarie; Hatzfeld, Mechthild

    2018-05-22

    Desmosomes are essential for strong intercellular adhesion and are abundant in tissues exposed to mechanical strain. At the same time, desmosomes need to be dynamic to allow for remodeling of epithelia during differentiation or wound healing. Phosphorylation of desmosomal plaque proteins appears to be essential for desmosome dynamics. However, the mechanisms of how context-dependent post-translational modifications regulate desmosome formation, dynamics or stability are incompletely understood. Here, we show that growth factor signaling regulates the phosphorylation-dependent association of plakophilins 1 and 3 (PKP1 and PKP3) with 14-3-3 protein isoforms, and uncover unique and partially antagonistic functions of members of the 14-3-3 family in the regulation of desmosomes. 14-3-3γ associated primarily with cytoplasmic PKP1 phosphorylated at S155 and destabilized intercellular cohesion of keratinocytes by reducing its incorporation into desmosomes. In contrast, 14-3-3σ (also known as stratifin, encoded by SFN ) interacted preferentially with S285-phosphorylated PKP3 to promote its accumulation at tricellular contact sites, leading to stable desmosomes. Taken together, our study identifies a new layer of regulation of intercellular adhesion by 14-3-3 proteins. © 2018. Published by The Company of Biologists Ltd.

  8. 21 CFR 876.5980 - Gastrointestinal tube and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., gastrointestinal string and tubes to locate internal bleeding, double lumen tube for intestinal decompression or... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Gastrointestinal tube and accessories. 876.5980... (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5980 Gastrointestinal...

  9. 21 CFR 876.5980 - Gastrointestinal tube and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., gastrointestinal string and tubes to locate internal bleeding, double lumen tube for intestinal decompression or... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Gastrointestinal tube and accessories. 876.5980... (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5980 Gastrointestinal...

  10. 21 CFR 876.5980 - Gastrointestinal tube and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., gastrointestinal string and tubes to locate internal bleeding, double lumen tube for intestinal decompression or... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Gastrointestinal tube and accessories. 876.5980... (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5980 Gastrointestinal...

  11. 21 CFR 876.5980 - Gastrointestinal tube and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., gastrointestinal string and tubes to locate internal bleeding, double lumen tube for intestinal decompression or... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Gastrointestinal tube and accessories. 876.5980... (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5980 Gastrointestinal...

  12. 21 CFR 884.4900 - Obstetric table and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Devices § 884.4900 Obstetric table and accessories. (a) Identification. An obstetric table is a device with adjustable sections designed to support a patient in the various positions required during...: patient equipment, support attachments, and cabinets for warming instruments and disposing of wastes. (b...

  13. 21 CFR 884.6190 - Assisted reproductive microscopes and microscope accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Assisted Reproduction... or embryos. Variations of microscopes and accessories used for these purposes would include phase...

  14. Negative regulation of multifunctional Ca2+/calmodulin-dependent protein kinases: physiological and pharmacological significance of protein phosphatases

    PubMed Central

    Ishida, A; Sueyoshi, N; Shigeri, Y; Kameshita, I

    2008-01-01

    Multifunctional Ca2+/calmodulin-dependent protein kinases (CaMKs) play pivotal roles in intracellular Ca2+ signaling pathways. There is growing evidence that CaMKs are involved in the pathogenic mechanisms underlying various human diseases. In this review, we begin by briefly summarizing our knowledge of the involvement of CaMKs in the pathogenesis of various diseases suggested to be caused by the dysfunction/dysregulation or aberrant expression of CaMKs. It is widely known that the activities of CaMKs are strictly regulated by protein phosphorylation/dephosphorylation of specific phosphorylation sites. Since phosphorylation status is balanced by protein kinases and protein phosphatases, the mechanism of dephosphorylation/deactivation of CaMKs, corresponding to their ‘switching off', is extremely important, as is the mechanism of phosphorylation/activation corresponding to their ‘switching on'. Therefore, we focus on the regulation of multifunctional CaMKs by protein phosphatases. We summarize the current understanding of negative regulation of CaMKs by protein phosphatases. We also discuss the biochemical properties and physiological significance of a protein phosphatase that we designated as Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP), and those of its homologue CaMKP-N. Pharmacological applications of CaMKP inhibitors are also discussed. These compounds may be useful not only for exploring the physiological functions of CaMKP/CaMKP-N, but also as novel chemotherapies for various diseases. PMID:18454172

  15. Regulation of blood-testis barrier by actin binding proteins and protein kinases

    PubMed Central

    Li, Nan; Tang, Elizabeth I.; Cheng, C. Yan

    2016-01-01

    The blood-testis barrier (BTB) is an important ultrastructure in the testis since the onset of spermatogenesis coincides with the establishment of a functional barrier in rodents and humans. It is also noted that a delay in the assembly of a functional BTB following treatment of neonatal rats with drugs such as diethylstilbestrol or adjudin also delays the first wave of spermiation. While the BTB is one of the tightest blood-tissue barriers, it undergoes extensive remodeling, in particular at stage VIII of the epithelial cycle to facilitate the transport of preleptotene spermatocytes connected in clones across the immunological barrier. Without this timely transport of preleptotene spermatocytes derived from type B spermatogonia, meiosis will be arrested, causing aspermatogenesis. Yet the biology and regulation of the BTB remains largely unexplored since the morphological studies in the 1970s. Recent studies, however, have shed new light on the biology of the BTB. Herein, we critically evaluate some of these findings, illustrating that the Sertoli cell BTB is regulated by actin binding proteins (ABPs), likely supported by non-receptor protein kinases, to modulate the organization of actin microfilament bundles at the site. Furthermore, microtubule (MT)-based cytoskeleton is also working in concert with the actin-based cytoskeleton to confer BTB dynamics. This timely review provides an update on the unique biology and regulation of the BTB based on the latest findings in the field, focusing on the role of ABPs and non-receptor protein kinases. PMID:26628556

  16. 21 CFR 876.4300 - Endoscopic electrosurgical unit and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Endoscopic electrosurgical unit and accessories. (a) Identification. An endoscopic electrosurgical unit and... device includes the electrosurgical generator, patient plate, electric biopsy forceps, electrode, flexible snare, electrosurgical alarm system, electrosurgical power supply unit, electrical clamp, self...

  17. The β-Arrestins: Multifunctional Regulators of G Protein-coupled Receptors*

    PubMed Central

    Smith, Jeffrey S.; Rajagopal, Sudarshan

    2016-01-01

    The β-arrestins (βarrs) are versatile, multifunctional adapter proteins that are best known for their ability to desensitize G protein-coupled receptors (GPCRs), but also regulate a diverse array of cellular functions. To signal in such a complex fashion, βarrs adopt multiple conformations and are regulated at multiple levels to differentially activate downstream pathways. Recent structural studies have demonstrated that βarrs have a conserved structure and activation mechanism, with plasticity of their structural fold, allowing them to adopt a wide array of conformations. Novel roles for βarrs continue to be identified, demonstrating the importance of these dynamic regulators of cellular signaling. PMID:26984408

  18. 21 CFR 884.4100 - Endoscopic electrocautery and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endoscopic electrocautery and accessories. 884.4100 Section 884.4100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ammeters: continue electrode activation for 5 seconds after the visual endpoint (tissue blanching) is...

  19. 21 CFR 890.3025 - Prosthetic and orthotic accessory.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Prosthetic and orthotic accessory. 890.3025 Section 890.3025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3025...

  20. 21 CFR 890.3025 - Prosthetic and orthotic accessory.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Prosthetic and orthotic accessory. 890.3025 Section 890.3025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3025...

  1. 21 CFR 890.3025 - Prosthetic and orthotic accessory.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Prosthetic and orthotic accessory. 890.3025 Section 890.3025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3025...

  2. 21 CFR 890.3025 - Prosthetic and orthotic accessory.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Prosthetic and orthotic accessory. 890.3025 Section 890.3025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3025...

  3. 21 CFR 890.3025 - Prosthetic and orthotic accessory.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Prosthetic and orthotic accessory. 890.3025 Section 890.3025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3025...

  4. Quality detection system and method of micro-accessory based on microscopic vision

    NASA Astrophysics Data System (ADS)

    Li, Dongjie; Wang, Shiwei; Fu, Yu

    2017-10-01

    Considering that the traditional manual detection of micro-accessory has some problems, such as heavy workload, low efficiency and large artificial error, a kind of quality inspection system of micro-accessory has been designed. Micro-vision technology has been used to inspect quality, which optimizes the structure of the detection system. The stepper motor is used to drive the rotating micro-platform to transfer quarantine device and the microscopic vision system is applied to get graphic information of micro-accessory. The methods of image processing and pattern matching, the variable scale Sobel differential edge detection algorithm and the improved Zernike moments sub-pixel edge detection algorithm are combined in the system in order to achieve a more detailed and accurate edge of the defect detection. The grade at the edge of the complex signal can be achieved accurately by extracting through the proposed system, and then it can distinguish the qualified products and unqualified products with high precision recognition.

  5. Flow-dependent regulation of endothelial nitric oxide synthase: role of protein kinases

    NASA Technical Reports Server (NTRS)

    Boo, Yong Chool; Jo, Hanjoong

    2003-01-01

    Vascular endothelial cells are directly and continuously exposed to fluid shear stress generated by blood flow. Shear stress regulates endothelial structure and function by controlling expression of mechanosensitive genes and production of vasoactive factors such as nitric oxide (NO). Though it is well known that shear stress stimulates NO production from endothelial nitric oxide synthase (eNOS), the underlying molecular mechanisms remain unclear and controversial. Shear-induced production of NO involves Ca2+/calmodulin-independent mechanisms, including phosphorylation of eNOS at several sites and its interaction with other proteins, including caveolin and heat shock protein-90. There have been conflicting results as to which protein kinases-protein kinase A, protein kinase B (Akt), other Ser/Thr protein kinases, or tyrosine kinases-are responsible for shear-dependent eNOS regulation. The functional significance of each phosphorylation site is still unclear. We have attempted to summarize the current status of understanding in shear-dependent eNOS regulation.

  6. Incidental gastric accessory spleen during laparoscopic sleeve gastrectomy.

    PubMed

    Almazeedi, Sulaiman; Alhaddad, Eliana; Al-Khithr, Talal; Alhunaidi, Mohammed

    2017-01-01

    Bariatric surgery has shown to produce the most predictable and tangible results for weight loss, with laparoscopic sleeve gastrectomy's being the most popular one of them. However, the occurrence of previously undiagnosed diseases can be encountered during bariatric operations. The work has been reported in line with the SCARE criteria. This is the case of a 54year old morbidly obese female, presenting to our hospital for a laparoscopic sleeve gastrectomy. During her procedure, it was discovered that she has an accessory spleen on the fundus of her stomach. The decision was made to resect it with the specimen of the stomach for histopathalogical examination. Incidental findings during routine bariatric surgery are a common occurance, and therefore prompt and effective intra-op management is key to the prognosis of the patient. Accessory spleens, although uncommon, tend to be asymptomatic. However, if undiagnosed, could present with dangerous consequences. Copyright © 2017. Published by Elsevier Ltd.

  7. Homeostatic regulation of protein intake: in search of a mechanism

    PubMed Central

    Reed, Scott D.; Henagan, Tara M.

    2012-01-01

    Free-living organisms must procure adequate nutrition by negotiating an environment in which both the quality and quantity of food vary markedly. Recent decades have seen marked progress in our understanding of neural regulation of feeding behavior. However, this progress has occurred largely in the context of energy intake, despite the fact that food intake is influenced by more than just the energy content of the diet. A large number of behavioral studies indicate that both the quantity and quality of dietary protein can markedly influence food intake. High-protein diets tend to reduce intake, low-protein diets tend to increase intake, and rodent models seem to self-select between diets in order to meet protein requirements and avoid diets that are imbalanced in amino acids. Recent work suggests that the amino acid leucine regulates food intake by altering mTOR and AMPK signaling in the hypothalamus, while activation of GCN2 within the anterior piriform cortex contributes to the detection and avoidance of amino acid-imbalanced diets. This review focuses on the role that these and other signaling systems may play in mediating the homeostatic regulation of protein balance, and in doing so, highlights our lack of knowledge regarding the physiological and neurobiological mechanisms that might underpin such a regulatory phenomenon. PMID:22319049

  8. Anatomical study of the accessory axillary vein in cadavers: a contribution to the axillary surgical approach.

    PubMed

    Felix, Valtuir Barbosa; Dos Santos, José André Bernardino; Fernandes, Katharina Jucá de Moraes; Cabral, Dhayanna Rolemberg Gama; Dos Santos, Carlos Adriano Silva; Rodrigues, Célio Fernando de Sousa; Lima, Jacqueline Silva Brito; Ramalho, Antônio José Casado

    2016-01-01

    The axillary vein is an important blood vessel that participates in drainage of the upper limb. Some individuals present a second axillary vein (accessory axillary vein), which is an important collateral drainage path. The goal of this study was to determine the incidence of the accessory axillary vein and to describe this vessel's topography. In this study, axillary dissections were carried out on twenty-four (24) human cadavers of both sexes that had been fixed with 10% formaldehyde. The upper limbs of the cadavers were still attached to the bodies and the axillary structures were preserved. Data collection was carried out and the axillary structures of the cadavers were compared. The incidence of accessory axillary veins was 58.3%, with no significant preference for sex or for side of the body. The accessory axillary vein originated from the lateral brachial vein in 39.28% of cases, from the common brachial vein in 35.71% of cases, and from the deep brachial vein in 25% of cases. Its high incidence and clinical relevance make the accessory axillary vein important for provision of collateral circulation in the event of traumatic injury to the axillary vein.

  9. Regulation of Protein Secretion Through Controlled Aggregation in the Endoplasmic Reticulum

    NASA Astrophysics Data System (ADS)

    Rivera, Victor M.; Wang, Xiurong; Wardwell, Scott; Courage, Nancy L.; Volchuk, Allen; Keenan, Terence; Holt, Dennis A.; Gilman, Michael; Orci, Lelio; Cerasoli, Frank; Rothman, James E.; Clackson, Tim

    2000-02-01

    A system for direct pharmacologic control of protein secretion was developed to allow rapid and pulsatile delivery of therapeutic proteins. A protein was engineered so that it accumulated as aggregates in the endoplasmic reticulum. Secretion was then stimulated by a synthetic small-molecule drug that induces protein disaggregation. Rapid and transient secretion of growth hormone and insulin was achieved in vitro and in vivo. A regulated pulse of insulin secretion resulted in a transient correction of serum glucose concentrations in a mouse model of hyperglycemia. This approach may make gene therapy a viable method for delivery of polypeptides that require rapid and regulated delivery.

  10. Decreased concentrations of soluble interleukin-1 receptor accessory protein levels in the peritoneal fluid of women with endometriosis.

    PubMed

    Michaud, Nadège; Al-Akoum, Mahéra; Gagnon, Geneviève; Girard, Karine; Blanchet, Pierre; Rousseau, Julie Anne; Akoum, Ali

    2011-12-01

    Interleukin 1 (IL1) may play an important role in endometriosis-associated pelvic inflammation, and natural specific inhibitors, including soluble IL1 receptor accessory protein (sIL1RAcP) and soluble IL1 receptor type 2 (sIL1R2), are critical for counterbalancing the pleiotropic effects of IL1. The objective of this study was to evaluate the levels of sIL1RAcP, together with those of sIL1R2 and IL1β, in the peritoneal fluid of women with and without endometriosis. Peritoneal fluid samples were obtained at laparoscopy and assessed by ELISA. sIL1RAcP concentrations were reduced in endometriosis stages I-II and III-IV. sIL1R2 concentrations were decreased, and those of IL1β were significantly increased in endometriosis stages I-II. sIL1RAcP and sIL1R2 concentrations were significantly decreased in the secretory phase of the menstrual cycle, and IL1β concentrations were elevated in the proliferative and the secretory phases. sIL1RAcP and sIL1R2 concentrations were reduced in women with endometriosis who were infertile, fertile, suffering from pelvic pain or pain-free. However, IL1β concentrations were significantly reduced in women with endometriosis who were infertile or had pelvic pain. These changes may exacerbate the local peritoneal inflammatory reaction observed in women with endometriosis and contribute to endometriosis pathophysiology and the major symptoms of this disease. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  11. HypoxiaDB: a database of hypoxia-regulated proteins

    PubMed Central

    Khurana, Pankaj; Sugadev, Ragumani; Jain, Jaspreet; Singh, Shashi Bala

    2013-01-01

    There has been intense interest in the cellular response to hypoxia, and a large number of differentially expressed proteins have been identified through various high-throughput experiments. These valuable data are scattered, and there have been no systematic attempts to document the various proteins regulated by hypoxia. Compilation, curation and annotation of these data are important in deciphering their role in hypoxia and hypoxia-related disorders. Therefore, we have compiled HypoxiaDB, a database of hypoxia-regulated proteins. It is a comprehensive, manually-curated, non-redundant catalog of proteins whose expressions are shown experimentally to be altered at different levels and durations of hypoxia. The database currently contains 72 000 manually curated entries taken on 3500 proteins extracted from 73 peer-reviewed publications selected from PubMed. HypoxiaDB is distinctive from other generalized databases: (i) it compiles tissue-specific protein expression changes under different levels and duration of hypoxia. Also, it provides manually curated literature references to support the inclusion of the protein in the database and establish its association with hypoxia. (ii) For each protein, HypoxiaDB integrates data on gene ontology, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway, protein–protein interactions, protein family (Pfam), OMIM (Online Mendelian Inheritance in Man), PDB (Protein Data Bank) structures and homology to other sequenced genomes. (iii) It also provides pre-compiled information on hypoxia-proteins, which otherwise requires tedious computational analysis. This includes information like chromosomal location, identifiers like Entrez, HGNC, Unigene, Uniprot, Ensembl, Vega, GI numbers and Genbank accession numbers associated with the protein. These are further cross-linked to respective public databases augmenting HypoxiaDB to the external repositories. (iv) In addition, HypoxiaDB provides an online sequence-similarity search tool for

  12. Solution NMR structure of CsgE: Structural insights into a chaperone and regulator protein important for functional amyloid formation.

    PubMed

    Shu, Qin; Krezel, Andrzej M; Cusumano, Zachary T; Pinkner, Jerome S; Klein, Roger; Hultgren, Scott J; Frieden, Carl

    2016-06-28

    Curli, consisting primarily of major structural subunit CsgA, are functional amyloids produced on the surface of Escherichia coli, as well as many other enteric bacteria, and are involved in cell colonization and biofilm formation. CsgE is a periplasmic accessory protein that plays a crucial role in curli biogenesis. CsgE binds to both CsgA and the nonameric pore protein CsgG. The CsgG-CsgE complex is the curli secretion channel and is essential for the formation of the curli fibril in vivo. To better understand the role of CsgE in curli formation, we have determined the solution NMR structure of a double mutant of CsgE (W48A/F79A) that appears to be similar to the wild-type (WT) protein in overall structure and function but does not form mixed oligomers at NMR concentrations similar to the WT. The well-converged structure of this mutant has a core scaffold composed of a layer of two α-helices and a layer of three-stranded antiparallel β-sheet with flexible N and C termini. The structure of CsgE fits well into the cryoelectron microscopy density map of the CsgG-CsgE complex. We highlight a striking feature of the electrostatic potential surface in CsgE structure and present an assembly model of the CsgG-CsgE complex. We suggest a structural mechanism of the interaction between CsgE and CsgA. Understanding curli formation can provide the information necessary to develop treatments and therapeutic agents for biofilm-related infections and may benefit the prevention and treatment of amyloid diseases. CsgE could establish a paradigm for the regulation of amyloidogenesis because of its unique role in curli formation.

  13. 21 CFR 884.4150 - Bipolar endoscopic coagulator-cutter and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... high frequency electrical current through tissue between two electrical contacts of a probe. This generic type of device may include the following accessories: an electrical generator, probes, and...

  14. 21 CFR 884.4150 - Bipolar endoscopic coagulator-cutter and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... high frequency electrical current through tissue between two electrical contacts of a probe. This generic type of device may include the following accessories: an electrical generator, probes, and...

  15. 21 CFR 884.4150 - Bipolar endoscopic coagulator-cutter and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... high frequency electrical current through tissue between two electrical contacts of a probe. This generic type of device may include the following accessories: an electrical generator, probes, and...

  16. 21 CFR 884.4150 - Bipolar endoscopic coagulator-cutter and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... high frequency electrical current through tissue between two electrical contacts of a probe. This generic type of device may include the following accessories: an electrical generator, probes, and...

  17. 21 CFR 884.4900 - Obstetric table and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Obstetric table and accessories. 884.4900 Section 884.4900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...: patient equipment, support attachments, and cabinets for warming instruments and disposing of wastes. (b...

  18. 21 CFR 878.4160 - Surgical camera and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Surgical camera and accessories. 878.4160 Section 878.4160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4160 Surgical camera...

  19. 21 CFR 878.4350 - Cryosurgical unit and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cryosurgical unit and accessories. 878.4350 Section 878.4350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4350 Cryosurgical unit...

  20. 21 CFR 878.4160 - Surgical camera and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Surgical camera and accessories. 878.4160 Section 878.4160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4160 Surgical camera...

  1. 21 CFR 878.4160 - Surgical camera and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Surgical camera and accessories. 878.4160 Section 878.4160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4160 Surgical camera...

  2. 21 CFR 878.4350 - Cryosurgical unit and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cryosurgical unit and accessories. 878.4350 Section 878.4350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4350 Cryosurgical unit...

  3. 21 CFR 878.4350 - Cryosurgical unit and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cryosurgical unit and accessories. 878.4350 Section 878.4350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4350 Cryosurgical unit...

  4. 21 CFR 878.4160 - Surgical camera and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Surgical camera and accessories. 878.4160 Section 878.4160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4160 Surgical camera...

  5. 21 CFR 878.4160 - Surgical camera and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Surgical camera and accessories. 878.4160 Section 878.4160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4160 Surgical camera...

  6. 21 CFR 878.4350 - Cryosurgical unit and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cryosurgical unit and accessories. 878.4350 Section 878.4350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4350 Cryosurgical unit...

  7. Correction of accessory axillary breast tissue without visible scar.

    PubMed

    Kim, Young Soo

    2004-01-01

    Various methods for correction of accessory axillary breast tissue have been proposed, including simple excision, diamond-shaped excision, a Y-V technique, and lipoplasty. We present an effective method for correction of a prominent axillary mound that combines lipoplasty with excision of accessory breast tissue along the axillary transverse line. Preoperative markings included an incision within the natural wrinkle line in the axillary fold, and demarcation of areas in which lipoplasty and excision were to be performed. After lipoplasty, deep dissection was performed to isolate and remove accessory breast tissue and excess fat tissue. A compression dressing was applied for 1 to 2 weeks postoperatively, and the patient was instructed to wear a sports bra for 1 to 2 months after removal of the dressing. We treated 7 patients using this procedure between October 1999 and March 2003. No major postoperative complications were detected and recurrence was not noted during the follow-up periods. Aesthetic results were satisfactory. We believe that a procedure that combines lipoplasty and excision provides numerous advantages as a surgical option in treating a prominent axillary mound. The main advantage is that the final scar is laid in the natural axillary fold, rendering scars less conspicuous and eliminating the need to remove excess skin. The one disadvantage was that elevation of the skin flap via small, remote incisions initially produced surgical difficulties, but these were overcome with experience.

  8. 21 CFR 876.5090 - Suprapubic urological catheter and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... accessories is a flexible tubular device that is inserted through the abdominal wall into the urinary bladder with the aid of a trocar and cannula. The device is used to pass fluids to and from the urinary tract...

  9. INTERIOR VIEW OF BATHROOM 2. SHOWING ORIGINAL TILE. CERAMIC ACCESSORIES, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    INTERIOR VIEW OF BATHROOM 2. SHOWING ORIGINAL TILE. CERAMIC ACCESSORIES, AND MARBLE THRESHOLD. VIEW FACING EAST. - Hickam Field, Officers' Housing Type G, 205 Seventh Street, Honolulu, Honolulu County, HI

  10. Regulation of neuronal communication by G protein-coupled receptors.

    PubMed

    Huang, Yunhong; Thathiah, Amantha

    2015-06-22

    Neuronal communication plays an essential role in the propagation of information in the brain and requires a precisely orchestrated connectivity between neurons. Synaptic transmission is the mechanism through which neurons communicate with each other. It is a strictly regulated process which involves membrane depolarization, the cellular exocytosis machinery, neurotransmitter release from synaptic vesicles into the synaptic cleft, and the interaction between ion channels, G protein-coupled receptors (GPCRs), and downstream effector molecules. The focus of this review is to explore the role of GPCRs and G protein-signaling in neurotransmission, to highlight the function of GPCRs, which are localized in both presynaptic and postsynaptic membrane terminals, in regulation of intrasynaptic and intersynaptic communication, and to discuss the involvement of astrocytic GPCRs in the regulation of neuronal communication. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  11. Ubiquitin-Dependent Degradation of Mitochondrial Proteins Regulates Energy Metabolism.

    PubMed

    Lavie, Julie; De Belvalet, Harmony; Sonon, Sessinou; Ion, Ana Madalina; Dumon, Elodie; Melser, Su; Lacombe, Didier; Dupuy, Jean-William; Lalou, Claude; Bénard, Giovanni

    2018-06-05

    The ubiquitin proteasome system (UPS) regulates many cellular functions by degrading key proteins. Notably, the role of UPS in regulating mitochondrial metabolic functions is unclear. Here, we show that ubiquitination occurs in different mitochondrial compartments, including the inner mitochondrial membrane, and that turnover of several metabolic proteins is UPS dependent. We specifically detailed mitochondrial ubiquitination and subsequent UPS-dependent degradation of succinate dehydrogenase subunit A (SDHA), which occurred when SDHA was minimally involved in mitochondrial energy metabolism. We demonstrate that SDHA ubiquitination occurs inside the organelle. In addition, we show that the specific inhibition of SDHA degradation by UPS promotes SDHA-dependent oxygen consumption and increases ATP, malate, and citrate levels. These findings suggest that the mitochondrial metabolic machinery is also regulated by the UPS. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Down-regulation of adenosine monophosphate-activated protein kinase activity: A driver of cancer.

    PubMed

    He, Xiaoling; Li, Cong; Ke, Rong; Luo, Lingyu; Huang, Deqiang

    2017-04-01

    Adenosine monophosphate-activated protein kinase (AMPK), a serine/threonine protein kinase, is known as "intracellular energy sensor and regulator." AMPK regulates multiple cellular processes including protein and lipid synthesis, cell proliferation, invasion, migration, and apoptosis. Moreover, AMPK plays a key role in the regulation of "Warburg effect" in cancer cells. AMPK activity is down-regulated in most tumor tissues compared with the corresponding adjacent paracancerous or normal tissues, indicating that the decline in AMPK activity is closely associated with the development and progression of cancer. Therefore, understanding the mechanism of AMPK deactivation during cancer progression is of pivotal importance as it may identify AMPK as a valid therapeutic target for cancer treatment. Here, we review the mechanisms by which AMPK is down-regulated in cancer.

  13. Regulation of GABAA receptors by fragile X mental retardation protein

    PubMed Central

    Liu, Baosong; Li, Lijun; Chen, Juan; Wang, Zefen; Li, Zhiqiang; Wan, Qi

    2013-01-01

    Fragile X syndrome (FXS) is caused by the loss of fragile X mental retardation protein (FMRP). The deficiency of GABAA receptors (GABAARs) is implicated in FXS. However, the underlying mechanisms remain unclear. To investigate the effect of FMRP on GABAARs, we transfected FMRP cDNAs in rat cortical neurons. We measured the protein expression of GABAARs and phosphatase PTEN, and recorded GABAAR-mediated whole-cell currents in the transfected neurons. We show that the transfection of FMRP cDNAs causes increased protein expression of GABAARs in cortical neurons, but GABAAR-mediated whole-cell currents are not potentiated by FMRP transfection. These results suggest the possibility that intracellular signaling antagonizing GABAAR activity may play a role in inhibiting GABAAR function in FMRP-transfected neurons. We further show that FMRP transfection results in an enhanced protein expression of PTEN, which contributes to the inhibition of GABAAR function in FMRP-transfected neurons. These results indicate that GABAARs are regulated by FMRP through both an up-regulation of GABAAR expression and a PTEN enhancement-induced inhibition of GABAAR function, suggesting that an abnormal regulation of GABAAR and PTEN by the loss of FMRP underlies the pathogenesis of FXS. PMID:24044036

  14. Persistent Increase in Blood Pressure After Renal Nerve Stimulation in Accessory Renal Arteries After Sympathetic Renal Denervation.

    PubMed

    de Jong, Mark R; Hoogerwaard, Annemiek F; Gal, Pim; Adiyaman, Ahmet; Smit, Jaap Jan J; Delnoy, Peter Paul H M; Ramdat Misier, Anand R; van Hasselt, Boudewijn A A M; Heeg, Jan-Evert; le Polain de Waroux, Jean-Benoit; Lau, Elizabeth O Y; Staessen, Jan A; Persu, Alexandre; Elvan, Arif

    2016-06-01

    Blood pressure response to renal denervation is highly variable, and the proportion of responders is disappointing. This may be partly because of accessory renal arteries too small for denervation, causing incomplete ablation. Renal nerve stimulation before and after renal denervation is a promising approach to assess completeness of renal denervation and may predict blood pressure response to renal denervation. The objective of the current study was to assess renal nerve stimulation-induced blood pressure increase before and after renal sympathetic denervation in main and accessory renal arteries of anaesthetized patients with drug-resistant hypertension. The study included 21 patients. Nine patients had at least 1 accessory renal artery in which renal denervation was not feasible. Renal nerve stimulation was performed in the main arteries of all patients and in accessory renal arteries of 6 of 9 patients with accessory arteries, both before and after renal sympathetic denervation. Renal nerve stimulation before renal denervation elicited a substantial increase in systolic blood pressure, both in main (25.6±2.9 mm Hg; P<0.001) and accessory (24.3±7.4 mm Hg; P=0.047) renal arteries. After renal denervation, renal nerve stimulation-induced systolic blood pressure increase was blunted in the main renal arteries (Δ systolic blood pressure, 8.6±3.7 mm Hg; P=0.020), but not in the nondenervated renal accessory renal arteries (Δ systolic blood pressure, 27.1±7.6 mm Hg; P=0.917). This residual source of renal sympathetic tone may result in persistent hypertension after ablation and partly account for the large response variability. © 2016 American Heart Association, Inc.

  15. The β-Arrestins: Multifunctional Regulators of G Protein-coupled Receptors.

    PubMed

    Smith, Jeffrey S; Rajagopal, Sudarshan

    2016-04-22

    The β-arrestins (βarrs) are versatile, multifunctional adapter proteins that are best known for their ability to desensitize G protein-coupled receptors (GPCRs), but also regulate a diverse array of cellular functions. To signal in such a complex fashion, βarrs adopt multiple conformations and are regulated at multiple levels to differentially activate downstream pathways. Recent structural studies have demonstrated that βarrs have a conserved structure and activation mechanism, with plasticity of their structural fold, allowing them to adopt a wide array of conformations. Novel roles for βarrs continue to be identified, demonstrating the importance of these dynamic regulators of cellular signaling. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Reproductive biology in Anophelinae mosquitoes (Diptera, Culicidae): Fine structure of the female accessory gland.

    PubMed

    Laghezza Masci, Valentina; Di Luca, Marco; Gambellini, Gabriella; Taddei, Anna Rita; Belardinelli, Maria Cristina; Guerra, Laura; Mazzini, Massimo; Fausto, Anna Maria

    2015-07-01

    The morphology and ultrastructure of female accessory reproductive glands of Anopheles maculipennis s.s., Anopheles labranchiae and Anopheles stephensi were investigated by light and electron microscopy. The reproductive system in these species is characterized by two ovaries, two lateral oviducts, a single spermatheca and a single accessory gland. The gland is globular and has a thin duct which empties into the vagina, near the opening of the spermathecal duct. Significant growth of the accessory reproductive gland is observed immediately after blood meal, but not at subsequent digestion steps. At ultrastructural level, the gland consists of functional glandular units belonging to type 3 ectodermal glands. The secretory cells are elongated and goblet shaped, with most of their cytoplasm and large nucleus in the basal part, close to the basement lamella. Finely fibrous electron-transparent material occupies the secretory cavity that is in contact with the end of a short efferent duct (ductule) emerging from the gland duct. The present study is the first detailed description of female accessory gland ultrastructure in Anophelinae and provides insights into the gland's functional role in the reproductive biology of these insects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Dexamethasone Regulates Cochlear Expression of Deafness-associated Proteins Myelin Protein Zero and Heat Shock Protein 70, as Revealed by iTRAQ Proteomics.

    PubMed

    Maeda, Yukihide; Fukushima, Kunihiro; Kariya, Shin; Orita, Yorihisa; Nishizaki, Kazunori

    2015-08-01

    Using proteomics, we aimed to identify the proteins differentially regulated by dexamethasone in the mouse cochlea based on mass-spectrometry data. Glucocorticoid therapy is widely used for many forms of sensorineural hearing loss; however, the molecular mechanism of its action in the cochlea remains poorly understood. Dexamethasone or control saline was intratympanically applied to the cochleae of mice. Twelve hours after application, proteins differentially regulated by dexamethasone in the cochlea were analyzed by isobaric Tag for Relative and Absolute Quantitation (iTRAQ)-mass spectrometry. Next, dexamethasone-dependent regulation of these proteins was verified in the cochleae of mice with noise-induced hearing loss (NIHL) and systemic administration of dexamethasone by western blotting. Immunolocalizations of these proteins were examined in cochleae with NIHL. A total of 247 proteins with a greater than 95% confidence interval of protein identification were found, and 11 differentially expressed proteins by dexamethasone were identified by the iTRAQ-mass spectrometry. One protein, myelin protein zero (Mpz), was upregulated (1.870 ± 0.201-fold change, p < 0.01) at 6 hours post-systemic dexamethasone and noise exposure in a mouse model of NIHL. Heat shock protein 70 (Hsp70) was downregulated (0.511 ± 0.274-fold change, p < 0.05) at 12 hours post-systemic dexamethasone. Immunohistochemistry confirmed Mpz localization to the efferent and afferent processes of the spiral neurons, whereas Hsp70 showed a more ubiquitous expression pattern in the cochlea. Both Mpz and Hsp70 have been reported to be closely associated with sensorineural hearing loss in humans. Dexamethasone significantly modulated the expression levels of these proteins in the cochleae of mice.

  18. 14 CFR 121.251 - Engine accessory section diaphragm.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Engine accessory section diaphragm. 121.251... REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Special Airworthiness Requirements § 121.251 Engine... complies with § 121.247 must be provided on air-cooled engines to isolate the engine power section and all...

  19. 14 CFR 121.251 - Engine accessory section diaphragm.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Engine accessory section diaphragm. 121.251... REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Special Airworthiness Requirements § 121.251 Engine... complies with § 121.247 must be provided on air-cooled engines to isolate the engine power section and all...

  20. 14 CFR 121.251 - Engine accessory section diaphragm.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Engine accessory section diaphragm. 121.251... REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Special Airworthiness Requirements § 121.251 Engine... complies with § 121.247 must be provided on air-cooled engines to isolate the engine power section and all...

  1. 14 CFR 121.251 - Engine accessory section diaphragm.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Engine accessory section diaphragm. 121.251... REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Special Airworthiness Requirements § 121.251 Engine... complies with § 121.247 must be provided on air-cooled engines to isolate the engine power section and all...

  2. [Clinicopathological analyses of accessory breast cancer: a report of 22 cases].

    PubMed

    Wang, Haotian; Duan, Jingjing; Xin, Fei; Cao, Xuchen

    2015-01-27

    To explore the clinicopathological characteristics, diagnosis, multi-disciplinary therapy and prognosis of accessory breast cancer. The clinical data were retrospectively analyzed for 22 patients with accessory breast cancer from December 2000 and September 2013. Three patients underwent breast-conserving local wide excision of tumor plus axillary lymph node dissection while the remainder had Auchincloss or Halsted mastectomy. The most common histological type was infiltrating ductal carcinoma (n = 16, 72%) and one of them was associated with mucous adenocarcinoma. There were carcinoma simplex (n = 1), papillary adenocarcinoma (n = 1) and adenocarcinoma (n = 4). The most common pathological stages (according to AJCC Staging of Breast Cancer, 2002, 6th edition) were II (n = 15, 68%),I(n = 3), III (n = 4) and IV (n = 0). The median follow-up period was 3 (1-14) years. And the follow-up rate was 100%.Until October 2014, 2 patients died from metastasis and the remainder survived. Accessory breast cancer is rare and has a worse prognosis.Now the clinical diagnostic criteria to it remains controversial and the diagnosis is often late. A definite diagnosis is made on the basis of clinical characteristics, postoperative pathology and imaging examinations. And surgery remains a major option.

  3. Structural basis of lentiviral subversion of a cellular protein degradation pathway

    NASA Astrophysics Data System (ADS)

    Schwefel, David; Groom, Harriet C. T.; Boucherit, Virginie C.; Christodoulou, Evangelos; Walker, Philip A.; Stoye, Jonathan P.; Bishop, Kate N.; Taylor, Ian A.

    2014-01-01

    Lentiviruses contain accessory genes that have evolved to counteract the effects of host cellular defence proteins that inhibit productive infection. One such restriction factor, SAMHD1, inhibits human immunodeficiency virus (HIV)-1 infection of myeloid-lineage cells as well as resting CD4+ T cells by reducing the cellular deoxynucleoside 5'-triphosphate (dNTP) concentration to a level at which the viral reverse transcriptase cannot function. In other lentiviruses, including HIV-2 and related simian immunodeficiency viruses (SIVs), SAMHD1 restriction is overcome by the action of viral accessory protein x (Vpx) or the related viral protein r (Vpr) that target and recruit SAMHD1 for proteasomal degradation. The molecular mechanism by which these viral proteins are able to usurp the host cell's ubiquitination machinery to destroy the cell's protection against these viruses has not been defined. Here we present the crystal structure of a ternary complex of Vpx with the human E3 ligase substrate adaptor DCAF1 and the carboxy-terminal region of human SAMHD1. Vpx is made up of a three-helical bundle stabilized by a zinc finger motif, and wraps tightly around the disc-shaped DCAF1 molecule to present a new molecular surface. This adapted surface is then able to recruit SAMHD1 via its C terminus, making it a competent substrate for the E3 ligase to mark for proteasomal degradation. The structure reported here provides a molecular description of how a lentiviral accessory protein is able to subvert the cell's normal protein degradation pathway to inactivate the cellular viral defence system.

  4. 75 FR 41523 - Paris Accessories, Inc., Including On-Site Leased Workers From Job Connections, New Smithville...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-16

    ... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-71,106; TA-W-71,106A] Paris Accessories, Inc., Including On-Site Leased Workers From Job Connections, New Smithville, PA; Paris... Paris Accessories, Inc., including on-site leased workers from Job Connections, New Smithville...

  5. 76 FR 585 - In the Matter of Certain Handbags, Luggage, Accessories and Packaging Thereof; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-05

    ..., Accessories and Packaging Thereof; Notice of Investigation AGENCY: U.S. International Trade Commission. ACTION... packaging thereof by reason of infringement of U.S. Trademark Registration No. 297,594 (``the `594 trademark... certain handbags, luggage, accessories and packaging thereof that infringe the `594 trademark; the `625...

  6. PRAK, a novel protein kinase regulated by the p38 MAP kinase.

    PubMed Central

    New, L; Jiang, Y; Zhao, M; Liu, K; Zhu, W; Flood, L J; Kato, Y; Parry, G C; Han, J

    1998-01-01

    We have identified and cloned a novel serine/ threonine kinase, p38-regulated/activated protein kinase (PRAK). PRAK is a 471 amino acid protein with 20-30% sequence identity to the known MAP kinase-regulated protein kinases RSK1/2/3, MNK1/2 and MAPKAP-K2/3. PRAK was found to be expressed in all human tissues and cell lines examined. In HeLa cells, PRAK was activated in response to cellular stress and proinflammatory cytokines. PRAK activity was regulated by p38alpha and p38beta both in vitro and in vivo and Thr182 was shown to be the regulatory phosphorylation site. Activated PRAK in turn phosphorylated small heat shock protein 27 (HSP27) at the physiologically relevant sites. An in-gel kinase assay demonstrated that PRAK is a major stress-activated kinase that can phosphorylate small heat shock protein, suggesting a potential role for PRAK in mediating stress-induced HSP27 phosphorylation in vivo. PMID:9628874

  7. Anatomical study of the accessory axillary vein in cadavers: a contribution to the axillary surgical approach

    PubMed Central

    Felix, Valtuir Barbosa; dos Santos, José André Bernardino; Fernandes, Katharina Jucá de Moraes; Cabral, Dhayanna Rolemberg Gama; dos Santos, Carlos Adriano Silva; Rodrigues, Célio Fernando de Sousa; Lima, Jacqueline Silva Brito; Ramalho, Antônio José Casado

    2016-01-01

    Abstract Background The axillary vein is an important blood vessel that participates in drainage of the upper limb. Some individuals present a second axillary vein (accessory axillary vein), which is an important collateral drainage path. Objectives The goal of this study was to determine the incidence of the accessory axillary vein and to describe this vessel’s topography. Methods In this study, axillary dissections were carried out on twenty-four (24) human cadavers of both sexes that had been fixed with 10% formaldehyde. The upper limbs of the cadavers were still attached to the bodies and the axillary structures were preserved. Data collection was carried out and the axillary structures of the cadavers were compared. Results The incidence of accessory axillary veins was 58.3%, with no significant preference for sex or for side of the body. The accessory axillary vein originated from the lateral brachial vein in 39.28% of cases, from the common brachial vein in 35.71% of cases, and from the deep brachial vein in 25% of cases. Conclusions Its high incidence and clinical relevance make the accessory axillary vein important for provision of collateral circulation in the event of traumatic injury to the axillary vein.

  8. Identity and transfer of male reproductive gland proteins of the dengue vector mosquito, Aedes aegypti: potential tools for control of female feeding and reproduction

    PubMed Central

    Sirot, Laura K.; Poulson, Rebecca L.; McKenna, M. Caitlin; Girnary, Hussein; Wolfner, Mariana F.; Harrington, Laura C.

    2009-01-01

    Male reproductive gland proteins (mRGPs) impact the physiology and/or behavior of mated females in a broad range of organisms. We sought to identify mRGPs of the yellow fever mosquito, Aedes aegypti, the primary vector of dengue and yellow fever viruses. Earlier studies with Ae. aegypti demonstrated that “matrone” (a partially purified male reproductive accessory gland substance) or male accessory gland fluid injected into virgin female Ae. aegypti affect female sexual refractoriness, blood feeding and digestion, flight, ovarian development, and oviposition. Using bioinformatic comparisons to Drosophila melanogaster accessory gland proteins and mass spectrometry of proteins from Ae. aegypti male accessory glands and ejaculatory ducts (AG/ED) and female reproductive tracts, we identified 63 new putative Ae. aegypti mRGPs. Twenty-one of these proteins were found in the reproductive tract of mated females, but not of virgin females, suggesting that they are transferred from males to females during mating. Most of the putative mRGPs fall into the same protein classes as mRGPs in other organisms, although some appear to be evolving rapidly and lack identifiable homologs in Culex pipiens, Anopheles gambiae, and D. melanogaster. Our results identify candidate male-derived molecules that may have an important influence on behavior, survival and reproduction of female mosquitoes. PMID:18207079

  9. Transcriptional regulation of genes related to progesterone production.

    PubMed

    Mizutani, Tetsuya; Ishikane, Shin; Kawabe, Shinya; Umezawa, Akihiro; Miyamoto, Kaoru

    2015-01-01

    Steroid hormones are synthesized from cholesterol in various tissues, mainly in the adrenal glands and gonads. Because these lipid-soluble steroid hormones immediately diffuse through the cells in which they are produced, their secretion directly reflects the activity of the genes related to their production. Progesterone is important not only for luteinization and maintenance of pregnancy, but also as a substrate for most other steroids. Steroidogenic acute regulatory protein (STAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4) isomerase (3β-HSD) are well-known proteins essential for progesterone production. In addition to them, glutathione S-transferase A1-1 and A3-3 are shown to exert Δ(5)-Δ(4) isomerization activity to produce progesterone in a cooperative fashion with 3β-HSD. 5-Aminolevulinic acid synthase 1, ferredoxin 1, and ferredoxin reductase also play a role in steroidogenesis as accessory factors. Members of the nuclear receptor 5A (NR5A) family (steroidogenic factor 1 and liver receptor homolog 1) play a crucial role in the transcriptional regulation of these genes. The NR5A family activates these genes by binding to NR5A responsive elements present within their promoter regions, as well as to the elements far from their promoters. In addition, various NR5A-interacting proteins including peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear receptor subfamily 0, group B, member 1 (DAX-1), and CCAAT/enhancer-binding proteins (C/EBP) are involved in the transcription of NR5A target genes and regulate the transcription either positively or negatively under both basal and tropic hormone-stimulated conditions. In this review, we describe the transcriptional regulation of genes related to progesterone production.

  10. The FASTK family of proteins: emerging regulators of mitochondrial RNA biology

    PubMed Central

    Jourdain, Alexis A.; Popow, Johannes; de la Fuente, Miguel A.; Martinou, Jean-Claude

    2017-01-01

    Abstract The FASTK family proteins have recently emerged as key post-transcriptional regulators of mitochondrial gene expression. FASTK, the founding member and its homologs FASTKD1–5 are architecturally related RNA-binding proteins, each having a different function in the regulation of mitochondrial RNA biology, from mRNA processing and maturation to ribosome assembly and translation. In this review, we outline the structure, evolution and function of these FASTK proteins and discuss the individual role that each has in mitochondrial RNA biology. In addition, we highlight the aspects of FASTK research that still require more attention. PMID:29036396

  11. Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells

    PubMed Central

    Tsuchiya, Yugo; Peak-Chew, Sew Yeu; Newell, Clare; Miller-Aidoo, Sheritta; Mangal, Sriyash; Zhyvoloup, Alexander; Bakovic´, Jovana; Malanchuk, Oksana; Pereira, Gonçalo C.; Kotiadis, Vassilios; Szabadkai, Gyorgy; Duchen, Michael R.; Campbell, Mark; Cuenca, Sergio Rodriguez; Vidal-Puig, Antonio; James, Andrew M.; Murphy, Michael P.; Filonenko, Valeriy; Skehel, Mark

    2017-01-01

    Coenzyme A (CoA) is an obligatory cofactor in all branches of life. CoA and its derivatives are involved in major metabolic pathways, allosteric interactions and the regulation of gene expression. Abnormal biosynthesis and homeostasis of CoA and its derivatives have been associated with various human pathologies, including cancer, diabetes and neurodegeneration. Using an anti-CoA monoclonal antibody and mass spectrometry, we identified a wide range of cellular proteins which are modified by covalent attachment of CoA to cysteine thiols (CoAlation). We show that protein CoAlation is a reversible post-translational modification that is induced in mammalian cells and tissues by oxidising agents and metabolic stress. Many key cellular enzymes were found to be CoAlated in vitro and in vivo in ways that modified their activities. Our study reveals that protein CoAlation is a widespread post-translational modification which may play an important role in redox regulation under physiological and pathophysiological conditions. PMID:28341808

  12. Clothing/Apparel and Accessories Merchandising. A Suggested Interdisciplinary Guide.

    ERIC Educational Resources Information Center

    Wray, Ralph D.; Hayden, Margaret B.

    This curriculum guide contains three sections: introduction, curriculum material, and an annotated bibliography. Introductory information provides an overview of the clothing/apparel and accessories merchandising area, aptitudes needed, and career opportunities; discusses potential career ladders, which are divided into entry level, middle…

  13. Identification and characterization of proteins involved in rice urea and arginine catabolism.

    PubMed

    Cao, Feng-Qiu; Werner, Andrea K; Dahncke, Kathleen; Romeis, Tina; Liu, Lai-Hua; Witte, Claus-Peter

    2010-09-01

    Rice (Oryza sativa) production relies strongly on nitrogen (N) fertilization with urea, but the proteins involved in rice urea metabolism have not yet been characterized. Coding sequences for rice arginase, urease, and the urease accessory proteins D (UreD), F (UreF), and G (UreG) involved in urease activation were identified and cloned. The functionality of urease and the urease accessory proteins was demonstrated by complementing corresponding Arabidopsis (Arabidopsis thaliana) mutants and by multiple transient coexpression of the rice proteins in Nicotiana benthamiana. Secondary structure models of rice (plant) UreD and UreF proteins revealed a possible functional conservation to bacterial orthologs, especially for UreF. Using amino-terminally StrepII-tagged urease accessory proteins, an interaction between rice UreD and urease could be shown. Prokaryotic and eukaryotic urease activation complexes seem conserved despite limited protein sequence conservation for UreF and UreD. In plant metabolism, urea is generated by the arginase reaction. Rice arginase was transiently expressed as a carboxyl-terminally StrepII-tagged fusion protein in N. benthamiana, purified, and biochemically characterized (K(m) = 67 mm, k(cat) = 490 s(-1)). The activity depended on the presence of manganese (K(d) = 1.3 microm). In physiological experiments, urease and arginase activities were not influenced by the external N source, but sole urea nutrition imbalanced the plant amino acid profile, leading to the accumulation of asparagine and glutamine in the roots. Our data indicate that reduced plant performance with urea as N source is not a direct result of insufficient urea metabolism but may in part be caused by an imbalance of N distribution.

  14. Unfolded protein response regulation in keloid cells.

    PubMed

    Butler, Paris D; Wang, Zhen; Ly, Daphne P; Longaker, Michael T; Koong, Albert C; Yang, George P

    2011-05-01

    Keloids are a common form of pathologic wound healing characterized by excessive production of extracellular matrix. The unfolded protein response (UPR) is a cellular response to hypoxia, a component of the wound microenvironment, capable of protecting cells from the effects of over-accumulation of misfolded proteins. Since keloids have hypersecretion of extracellular matrix, we hypothesized that keloid fibroblasts (KFs) may have enhanced activation of the UPR compared with normal fibroblasts (NFs). KFs and NFs were placed in a hypoxia chamber for 0, 24, and 48h. We also used tunicamycin to specifically up-regulate the UPR. UPR activation was assayed by PCR for xbp-1 splicing and by immunoblotting with specific antibodies for the three UPR transducers. Nuclear localization of XBP-1 protein in KFs was confirmed by immunofluorescence. There is increased activation of XBP-1 protein in KFs compared with NFs following exposure to hypoxia. Pancreatic ER kinase (PERK) and ATF-6, two other pathways activated by the UPR, show comparable activation between KFs and NFs. We confirmed that there is enhanced activation of XBP-1 by demonstrating increased nuclear localization of XBP-1 using immunofluorescence. In contrast to our initial hypothesis that keloids would have broad activation of the UPR, we demonstrate here that there is a specific up-regulation of one facet of the UPR response. This may represent a specific molecular defect in KFs compared with NFs, and also suggests modulation of the UPR can be used in wound healing therapy. Published by Elsevier Inc.

  15. Targeting pH regulating proteins for cancer therapy-Progress and limitations.

    PubMed

    Parks, Scott K; Pouysségur, Jacques

    2017-04-01

    Tumour acidity induced by metabolic alterations and incomplete vascularisation sets cancer cells apart from normal cellular physiology. This distinguishing tumour characteristic has been an area of intense study, as cellular pH (pH i ) disturbances disrupt protein function and therefore multiple cellular processes. Tumour cells effectively utilise pH i regulating machinery present in normal cells with enhancements provided by additional oncogenic or hypoxia induced protein modifications. This overall improvement of pH regulation enables maintenance of an alkaline pH i in the continued presence of external acidification (pH e ). Considerable experimentation has revealed targets that successfully disrupt tumour pH i regulation in efforts to develop novel means to weaken or kill tumour cells. However, redundancy in these pH-regulating proteins, which include Na + /H + exchangers (NHEs), carbonic anhydrases (CAs), Na + /HCO 3 - co-transporters (NBCs) and monocarboxylate transporters (MCTs) has prevented effective disruption of tumour pH i when individual protein targeting is performed. Here we synthesise recent advances in understanding both normoxic and hypoxic pH regulating mechanisms in tumour cells with an ultimate focus on the disruption of tumour growth, survival and metastasis. Interactions between tumour acidity and other cell types are also proving to be important in understanding therapeutic applications such as immune therapy. Promising therapeutic developments regarding pH manipulation along with current limitations are highlighted to provide a framework for future research directives. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. 26 CFR 48.4062(a)-1 - Specific parts or accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., and Taxable Fuel Automotive and Related Items § 48.4062(a)-1 Specific parts or accessories. Spark plugs, storage batteries, leaf springs, coils, timers, and tire chains, which are suitable for use on or...

  17. Ethylene Rapidly Up-Regulates the Activities of Both Monomeric GTP-Binding Proteins and Protein Kinase(s) in Epicotyls of Pea1

    PubMed Central

    Moshkov, Igor E.; Novikova, Galina V.; Mur, Luis A.J.; Smith, Aileen R.; Hall, Michael A.

    2003-01-01

    It is demonstrated that, in etiolated pea (Pisum sativum) epicotyls, ethylene affects the activation of both monomeric GTP-binding proteins (monomeric G-proteins) and protein kinases. For monomeric G-proteins, the effect may be a rapid (2 min) and bimodal up-regulation, a transiently unimodal activation, or a transient down-regulation. Pretreatment with 1-methylcyclopropene abolishes the response to ethylene overall. Immunoprecipitation studies indicate that some of the monomeric G-proteins affected may be of the Rab class. Protein kinase activity is rapidly up-regulated by ethylene, the effect is inhibited by 1-methylcyclopropene, and the activation is bimodal. Immunoprecipitation indicates that the kinase(s) are of the MAP kinase ERK1 group. It is proposed that the data support the hypothesis that a transduction chain exists that is separate and antagonistic to that currently revealed by studies on Arabidopsis mutants. PMID:12692330

  18. FBXW10 is negatively regulated in transcription and expression level by protein O-GlcNAcylation.

    PubMed

    Feng, Zhou; Hui, Yan; Ling, Li; Xiaoyan, Liu; Yuqiu, Wang; Peng, Wang; Lianwen, Zhang

    2013-08-23

    Intricate cross-talks exist among multiple post-translational modifications that play critical roles in various cellular events, such as the control of gene expression and regulation of protein function. Here, the cross-talk between O-GlcNAcylation and ubiquitination was investigated in HEK293T cells. By PCR array, 84 ubiquitination-related genes were explored in transcription level in response to the elevation of total protein O-GlcNAcylation due to over-expression of OGT, inhibition of OGA or GlcN treatment. Varied genes were transcriptionally regulated by using different method. But FBXW10, an F-box protein targeting specific proteins for ubiquitination, could be negatively regulated in all ways, suggesting its regulation by protein O-GlcNAcylation. By RT-PCR and Western blot analysis, it was found that FBXW10 could be sharply down-regulated in mRNA and protein level in GlcN-treated cells in a time-dependent way, in line with the enhancement of protein O-GlcNAcylation. It was also found that endogenous FBXW10 was modified by O-GlcNAc in HEK293T cells, implying O-GlcNAcylation might regulate FBXW10 in multiple levels. These findings indicate that O-GlcNAcylation is involved in the regulation of ubiquitination-related genes, and help us understand the cross-talk between O-GlcNAcylation and ubiquitination. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Accessory enzymes influence cellulase hydrolysis of the model substrate and the realistic lignocellulosic biomass.

    PubMed

    Sun, Fubao Fuebiol; Hong, Jiapeng; Hu, Jinguang; Saddler, Jack N; Fang, Xu; Zhang, Zhenyu; Shen, Song

    2015-11-01

    The potential of cellulase enzymes in the developing and ongoing "biorefinery" industry has provided a great motivation to develop an efficient cellulase mixture. Recent work has shown how important the role that the so-called accessory enzymes can play in an effective enzymatic hydrolysis. In this study, three newest Novozymes Cellic CTec cellulase preparations (CTec 1/2/3) were compared to hydrolyze steam pretreated lignocellulosic substrates and model substances at an identical FPA loading. These cellulase preparations were found to display significantly different hydrolytic performances irrelevant with the FPA. And this difference was even observed on the filter paper itself when the FPA based assay was revisited. The analysis of specific enzyme activity in cellulase preparations demonstrated that different accessory enzymes were mainly responsible for the discrepancy of enzymatic hydrolysis between diversified substrates and various cellulases. Such the active role of accessory enzymes present in cellulase preparations was finally verified by supplementation with β-glucosidase, xylanase and lytic polysaccharide monooxygenases AA9. This paper provides new insights into the role of accessory enzymes, which can further provide a useful reference for the rational customization of cellulase cocktails in order to realize an efficient conversion of natural lignocellulosic substrates. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Value of local electrogram characteristics predicting successful catheter ablation of left-versus right-sided accessory atrioventricular pathways by radiofrequency current.

    PubMed

    Lin, J L; Schie, J T; Tseng, C D; Chen, W J; Cheng, T F; Tsou, S S; Chen, J J; Tseng, Y Z; Lien, W P

    1995-01-01

    Despite similar guidance by local electrogram criteria, catheter ablation of right-sided accessory atrioventricular (AV) pathways by radiofrequency current has been less effective than that of left-sided ones. In order to elucidate the possible diversities in local electrosignal criteria, we systematically analyzed the morphological and timing characteristics of 215 bipolar local electrograms from catheter ablation sites of 65 left-sided accessory AV pathways and of 356 from those of 37 right-sided ones in 92 consecutive patients with Wolff-Parkinson-White syndrome or AV reentrant tachycardia incorporating concealed accessory AV pathways. After stepwise multivariate analysis, we selected the presence of a possible accessory pathway potential, local ventricular activation preceding QRS complex for 20 ms or more during ventricular insertion mapping, and the local retrograde ventriculoatrial (VA) continuity, local retrograde VA interval < or = 50 ms, electrogram stability (left-sided targets only), retrograde accessory pathway potential (right-sided targets only) during atrial insertion mapping, as independent local electrogram predictors for successful ablation of left- and right-sided accessory AV pathways. Combination of all local electrogram predictors could have moderate chance of success (80 and 51%) for the ventricular and atrial insertion ablation of left-sided accessory AV pathways, but only low probability of success (40% in ventricular insertion ablation) or very low sensitivity (12.5% in atrial insertion ablation) for right-sided ones. In conclusion, with the present approach, successful catheter ablation of right-sided accessory AV pathways, compared to left-sided ones, still necessitate a breakthrough in the precision mapping and the efficiency of energy delivery.

  1. TDP-43 regulates the microprocessor complex activity during in vitro neuronal differentiation.

    PubMed

    Di Carlo, Valerio; Grossi, Elena; Laneve, Pietro; Morlando, Mariangela; Dini Modigliani, Stefano; Ballarino, Monica; Bozzoni, Irene; Caffarelli, Elisa

    2013-12-01

    TDP-43 (TAR DNA-binding protein 43) is an RNA-binding protein implicated in RNA metabolism at several levels. Even if ubiquitously expressed, it is considered as a neuronal activity-responsive factor and a major signature for neurological pathologies, making the comprehension of its activity in the nervous system a very challenging issue. TDP-43 has also been described as an accessory component of the Drosha-DGCR8 (DiGeorge syndrome critical region gene 8) microprocessor complex, which is crucially involved in basal and tissue-specific RNA processing events. In the present study, we exploited in vitro neuronal differentiation systems to investigate the TDP-43 demand for the microprocessor function, focusing on both its canonical microRNA biosynthetic activity and its alternative role as a post-transcriptional regulator of gene expression. Our findings reveal a novel role for TDP-43 as an essential factor that controls the stability of Drosha protein during neuronal differentiation, thus globally affecting the production of microRNAs. We also demonstrate that TDP-43 is required for the Drosha-mediated regulation of Neurogenin 2, a master gene orchestrating neurogenesis, whereas post-transcriptional control of Dgcr8, another Drosha target, resulted to be TDP-43-independent. These results implicate a previously uncovered contribution of TDP-43 in regulating the abundance and the substrate specificity of the microprocessor complex and provide new insights into TDP-43 as a key player in neuronal differentiation.

  2. The nuclear import of ribosomal proteins is regulated by mTOR

    PubMed Central

    Kazyken, Dubek; Kaz, Yelimbek; Kiyan, Vladimir; Zhylkibayev, Assylbek A.; Chen, Chien-Hung; Agarwal, Nitin K.; Sarbassov, Dos D.

    2014-01-01

    Mechanistic target of rapamycin (mTOR) is a central component of the essential signaling pathway that regulates cell growth and proliferation by controlling anabolic processes in cells. mTOR exists in two distinct mTOR complexes known as mTORC1 and mTORC2 that reside mostly in cytoplasm. In our study, the biochemical characterization of mTOR led to discovery of its novel localization on nuclear envelope where it associates with a critical regulator of nuclear import Ran Binding Protein 2 (RanBP2). We show that association of mTOR with RanBP2 is dependent on the mTOR kinase activity that regulates the nuclear import of ribosomal proteins. The mTOR kinase inhibitors within thirty minutes caused a substantial decrease of ribosomal proteins in the nuclear but not cytoplasmic fraction. Detection of a nuclear accumulation of the GFP-tagged ribosomal protein rpL7a also indicated its dependence on the mTOR kinase activity. The nuclear abundance of ribosomal proteins was not affected by inhibition of mTOR Complex 1 (mTORC1) by rapamycin or deficiency of mTORC2, suggesting a distinctive role of the nuclear envelope mTOR complex in the nuclear import. Thus, we identified that mTOR in association with RanBP2 mediates the active nuclear import of ribosomal proteins. PMID:25294810

  3. The Fanconi Anemia C Protein Binds to and Regulates Stathmin-1 Phosphorylation

    PubMed Central

    Magron, Audrey; Elowe, Sabine; Carreau, Madeleine

    2015-01-01

    The Fanconi anemia (FA) proteins are involved in a signaling network that assures the safeguard of chromosomes. To understand the function of FA proteins in cellular division events, we investigated the interaction between Stathmin-1 (STMN1) and the FA group C (FANCC) protein. STMN1 is a ubiquitous cytosolic protein that regulates microtubule dynamics. STMN1 activities are regulated through phosphorylation-dephosphorylation mechanisms that control assembly of the mitotic spindle, and dysregulation of STMN1 phosphorylation is associated with mitotic aberrancies leading to chromosome instability and cancer progression. Using different biochemical approaches, we showed that FANCC interacts and co-localizes with STMN1 at centrosomes during mitosis. We also showed that FANCC is required for STMN1 phosphorylation, as mutations in FANCC reduced serine 16- and 38-phosphorylated forms of STMN1. Phosphorylation of STMN1 at serine 16 is likely an event dependent on a functional FA pathway, as it is reduced in FANCA- and FANCD2-mutant cells. Furthermore, FA-mutant cells exhibited mitotic spindle anomalies such as supernumerary centrosomes and shorter mitotic spindles. These results suggest that FA proteins participate in the regulation of cellular division via the microtubule-associated protein STMN1. PMID:26466335

  4. Regulated Eukaryotic DNA Replication Origin Firing with Purified Proteins

    PubMed Central

    Yeeles, Joseph T.P.; Deegan, Tom D.; Janska, Agnieszka; Early, Anne; Diffley, John F. X.

    2016-01-01

    Eukaryotic cells initiate DNA replication from multiple origins, which must be tightly regulated to promote precise genome duplication in every cell cycle. To accomplish this, initiation is partitioned into two temporally discrete steps: a double hexameric MCM complex is first loaded at replication origins during G1 phase, and then converted to the active CMG (Cdc45, MCM, GINS) helicase during S phase. Here we describe the reconstitution of budding yeast DNA replication initiation with 16 purified replication factors, made from 42 polypeptides. Origin-dependent initiation recapitulates regulation seen in vivo. Cyclin dependent kinase (CDK) inhibits MCM loading by phosphorylating the origin recognition complex (ORC) and promotes CMG formation by phosphorylating Sld2 and Sld3. Dbf4 dependent kinase (DDK) promotes replication by phosphorylating MCM, and can act either before or after CDK. These experiments define the minimum complement of proteins, protein kinase substrates and co-factors required for regulated eukaryotic DNA replication. PMID:25739503

  5. Regulated eukaryotic DNA replication origin firing with purified proteins.

    PubMed

    Yeeles, Joseph T P; Deegan, Tom D; Janska, Agnieszka; Early, Anne; Diffley, John F X

    2015-03-26

    Eukaryotic cells initiate DNA replication from multiple origins, which must be tightly regulated to promote precise genome duplication in every cell cycle. To accomplish this, initiation is partitioned into two temporally discrete steps: a double hexameric minichromosome maintenance (MCM) complex is first loaded at replication origins during G1 phase, and then converted to the active CMG (Cdc45-MCM-GINS) helicase during S phase. Here we describe the reconstitution of budding yeast DNA replication initiation with 16 purified replication factors, made from 42 polypeptides. Origin-dependent initiation recapitulates regulation seen in vivo. Cyclin-dependent kinase (CDK) inhibits MCM loading by phosphorylating the origin recognition complex (ORC) and promotes CMG formation by phosphorylating Sld2 and Sld3. Dbf4-dependent kinase (DDK) promotes replication by phosphorylating MCM, and can act either before or after CDK. These experiments define the minimum complement of proteins, protein kinase substrates and co-factors required for regulated eukaryotic DNA replication.

  6. The heat-shock protein Apg-2 binds to the tight junction protein ZO-1 and regulates transcriptional activity of ZONAB.

    PubMed

    Tsapara, Anna; Matter, Karl; Balda, Maria S

    2006-03-01

    The tight junction adaptor protein ZO-1 regulates intracellular signaling and cell proliferation. Its Src homology 3 (SH3) domain is required for the regulation of proliferation and binds to the Y-box transcription factor ZO-1-associated nucleic acid binding protein (ZONAB). Binding of ZO-1 to ZONAB results in cytoplasmic sequestration and hence inhibition of ZONAB's transcriptional activity. Here, we identify a new binding partner of the SH3 domain that modulates ZO-1-ZONAB signaling. Expression screening of a cDNA library with a fusion protein containing the SH3 domain yielded a cDNA coding for Apg-2, a member of the heat-shock protein 110 (Hsp 110) subfamily of Hsp70 heat-shock proteins, which is overexpressed in carcinomas. Regulated depletion of Apg-2 in Madin-Darby canine kidney cells inhibits G(1)/S phase progression. Apg-2 coimmunoprecipitates with ZO-1 and partially localizes to intercellular junctions. Junctional recruitment and coimmunoprecipitation with ZO-1 are stimulated by heat shock. Apg-2 competes with ZONAB for binding to the SH3 domain in vitro and regulates ZONAB's transcriptional activity in reporter gene assays. Our data hence support a model in which Apg-2 regulates ZONAB function by competing for binding to the SH3 domain of ZO-1 and suggest that Apg-2 functions as a regulator of ZO-1-ZONAB signaling in epithelial cells in response to cellular stress.

  7. The Heat-Shock Protein Apg-2 Binds to the Tight Junction Protein ZO-1 and Regulates Transcriptional Activity of ZONAB

    PubMed Central

    Tsapara, Anna; Matter, Karl; Balda, Maria S.

    2006-01-01

    The tight junction adaptor protein ZO-1 regulates intracellular signaling and cell proliferation. Its Src homology 3 (SH3) domain is required for the regulation of proliferation and binds to the Y-box transcription factor ZO-1-associated nucleic acid binding protein (ZONAB). Binding of ZO-1 to ZONAB results in cytoplasmic sequestration and hence inhibition of ZONAB's transcriptional activity. Here, we identify a new binding partner of the SH3 domain that modulates ZO-1–ZONAB signaling. Expression screening of a cDNA library with a fusion protein containing the SH3 domain yielded a cDNA coding for Apg-2, a member of the heat-shock protein 110 (Hsp 110) subfamily of Hsp70 heat-shock proteins, which is overexpressed in carcinomas. Regulated depletion of Apg-2 in Madin-Darby canine kidney cells inhibits G1/S phase progression. Apg-2 coimmunoprecipitates with ZO-1 and partially localizes to intercellular junctions. Junctional recruitment and coimmunoprecipitation with ZO-1 are stimulated by heat shock. Apg-2 competes with ZONAB for binding to the SH3 domain in vitro and regulates ZONAB's transcriptional activity in reporter gene assays. Our data hence support a model in which Apg-2 regulates ZONAB function by competing for binding to the SH3 domain of ZO-1 and suggest that Apg-2 functions as a regulator of ZO-1–ZONAB signaling in epithelial cells in response to cellular stress. PMID:16407410

  8. Regulators of G-protein signaling 4 in adrenal gland: localization, regulation, and role in aldosterone secretion.

    PubMed

    Romero, Damian G; Zhou, Ming Yi; Yanes, Licy L; Plonczynski, Maria W; Washington, Tanganika R; Gomez-Sanchez, Celso E; Gomez-Sanchez, Elise P

    2007-08-01

    Regulators of G-protein signaling (RGS proteins) interact with Galpha subunits of heterotrimeric G-proteins, accelerating the rate of GTP hydrolysis and finalizing the intracellular signaling triggered by the G-protein-coupled receptor (GPCR)-ligand interaction. Angiotensin II (Ang II) interacts with its GPCR in adrenal zona glomerulosa cells and triggers a cascade of intracellular signals that regulates steroidogenesis and proliferation. On screening for adrenal zona glomerulosa-specific genes, we found that RGS4 was exclusively localized in the zona glomerulosa of the rat adrenal cortex. We studied RGS4 expression and regulation in the rat adrenal gland, including the signaling pathways involved, as well as the role of RGS4 in steroidogenesis in human adrenocortical H295R cells. We reported that RGS4 mRNA expression in the rat adrenal gland was restricted to the adrenal zonal glomerulosa and upregulated by low-salt diet and Ang II infusion in rat adrenal glands in vivo. In H295R cells, Ang II caused a rapid and transient increase in RGS4 mRNA levels mediated by the calcium/calmodulin/calmodulin-dependent protein kinase and protein kinase C pathways. RGS4 overexpression by retroviral infection in H295R cells decreased Ang II-stimulated aldosterone secretion. In reporter assays, RGS4 decreased Ang II-mediated aldosterone synthase upregulation. In summary, RGS4 is an adrenal gland zona glomerulosa-specific gene that is upregulated by aldosterone secretagogues, in vivo and in vitro, and functions as a negative feedback of Ang II-triggered intracellular signaling. Alterations in RGS4 expression levels or functions may be involved in deregulations of Ang II signaling and abnormal aldosterone secretion.

  9. Changes in tissue protein synthesis are involved in regulating urea synthesis in rats given proteins of different quality.

    PubMed

    Tujioka, Kazuyo; Lyou, Sunok; Sano, Atushi; Hayase, Kazutoshi; Yokogoshi, Hidehiko

    2004-10-01

    The purpose of present study was to determine whether the regulation of urea synthesis is mediated through changes in supply of amino acids by protein synthesis and whether the concentration of ammonia, or activities of amino acid catabolizing enzymes, regulate urea synthesis when the dietary protein quality is manipulated. Experiments were done on three groups of rats given diets containing 10 g gluten, 10 g casein or 10 g whole egg protein/100 g for 10 d. The urinary excretion of urea, and the liver concentrations of glutamate, serine and alanine increased with a decrease in quality of dietary protein. The fractional and absolute rates of protein synthesis in tissues declined with the decrease in quality of dietary protein quality. The ammonia concentration in plasma and liver, and activities of hepatic amino acid catabolizing enzymes was not related to urea excretion under these conditions. These results suggest that the lower protein synthesis seen in tissues of rats given the lower quality of protein is likely to be one of the factors to increasing the supply of amino acids and stimulating urea synthesis.

  10. Novel Regulation of Ski Protein Stability and Endosomal Sorting by Actin Cytoskeleton Dynamics in Hepatocytes*

    PubMed Central

    Vázquez-Victorio, Genaro; Caligaris, Cassandre; Del Valle-Espinosa, Eugenio; Sosa-Garrocho, Marcela; González-Arenas, Nelly R.; Reyes-Cruz, Guadalupe; Briones-Orta, Marco A.; Macías-Silva, Marina

    2015-01-01

    TGF-β-induced antimitotic signals are highly regulated during cell proliferation under normal and pathological conditions, such as liver regeneration and cancer. Up-regulation of the transcriptional cofactors Ski and SnoN during liver regeneration may favor hepatocyte proliferation by inhibiting TGF-β signals. In this study, we found a novel mechanism that regulates Ski protein stability through TGF-β and G protein-coupled receptor (GPCR) signaling. Ski protein is distributed between the nucleus and cytoplasm of normal hepatocytes, and the molecular mechanisms controlling Ski protein stability involve the participation of actin cytoskeleton dynamics. Cytoplasmic Ski is partially associated with actin and localized in cholesterol-rich vesicles. Ski protein stability is decreased by TGF-β/Smads, GPCR/Rho signals, and actin polymerization, whereas GPCR/cAMP signals and actin depolymerization promote Ski protein stability. In conclusion, TGF-β and GPCR signals differentially regulate Ski protein stability and sorting in hepatocytes, and this cross-talk may occur during liver regeneration. PMID:25561741

  11. The Temporal Regulation of S Phase Proteins During G1

    PubMed Central

    Grant, Gavin D.; Cook, Jeanette G.

    2018-01-01

    Successful DNA replication requires intimate coordination with cell cycle progression. Prior to DNA replication initiation in S phase, a series of essential preparatory events in G1 phase ensures timely, complete, and precise genome duplication. Among the essential molecular processes are regulated transcriptional upregulation of genes that encode replication proteins, appropriate post-transcriptional control of replication factor abundance and activity, and the assembly of DNA-loaded protein complexes to license replication origins. In this chapter we describe these critical G1 events necessary for DNA replication and their regulation in the context of both cell cycle entry and cell cycle progression. PMID:29357066

  12. rbm47, a novel RNA binding protein, regulates zebrafish head development.

    PubMed

    Guan, Rui; El-Rass, Suzan; Spillane, David; Lam, Simon; Wang, Yuodong; Wu, Jing; Chen, Zhuchu; Wang, Anan; Jia, Zhengping; Keating, Armand; Hu, Jim; Wen, Xiao-Yan

    2013-12-01

    Vertebrate trunk induction requires inhibition of bone morphogenetic protein (BMP) signaling, whereas vertebrate head induction requires concerted inhibition of both Wnt and BMP signaling. RNA binding proteins play diverse roles in embryonic development and their roles in vertebrate head development remain to be elucidated. We first characterized the human RBM47 as an RNA binding protein that specifically binds RNA but not single-stranded DNA. Next, we knocked down rbm47 gene function in zebrafish using morpholinos targeting the start codon and exon-1/intron-1 splice junction. Down-regulation of rbm47 resulted in headless and small head phenotypes, which can be rescued by a wnt8a blocking morpholino. To further reveal the mechanism of rbm47's role in head development, microarrays were performed to screen genes differentially expressed in normal and knockdown embryos. epcam and a2ml were identified as the most significantly up- and down-regulated genes, respectively. The microarrays also confirmed up-regulation of several genes involved in head development, including gsk3a, otx2, and chordin, which are important regulators of Wnt signaling. Altogether, our findings reveal that Rbm47 is a novel RNA-binding protein critical for head formation and embryonic patterning during zebrafish embryogenesis which may act through a Wnt8a signaling pathway. Copyright © 2013 Wiley Periodicals, Inc.

  13. The regulation of smooth muscle contractility by zipper-interacting protein kinase.

    PubMed

    Ihara, Eikichi; MacDonald, Justin A

    2007-01-01

    Smooth muscle contractility is mainly regulated by phosphorylation of the 20 kDa myosin light chains (LC20), a process that is controlled by the opposing activities of myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP). Recently, intensive research has revealed that various protein kinase networks including Rho-kinase, integrin-linked kinase, zipper-interacting protein kinase (ZIPK), and protein kinase C (PKC) are involved in the regulation of LC20 phosphorylation and have important roles in modulating smooth muscle contractile responses to Ca2+ (i.e., Ca2+ sensitization and Ca2+ desensitization). Here, we review the general background and structure of ZIPK and summarize our current understanding of its involvement in a number of cell processes including cell death (apoptosis), cell motility, and smooth muscle contraction. ZIPK has been found to induce the diphosphorylation of LC20 at Ser-19 and Thr-18 in a Ca2+-independent manner and to regulate MLCP activity directly through its phosphorylation of the myosin-targeting subunit of MLCP or indirectly through its phosphorylation of the PKC-potentiated inhibitory protein of MLCP. Future investigations of ZIPK function in smooth muscle will undoubtably focus on determining the mechanisms that regulate its cellular activity, including the identification of upstream signaling pathways, the characterization of autoinhibitory domains and regulatory phosphorylation sites, and the development of specific inhibitor compounds.

  14. Double-bromo and extraterminal (BET) domain proteins regulate dendrite morphology and mechanosensory function

    PubMed Central

    Bagley, Joshua A.; Yan, Zhiqiang; Zhang, Wei; Wildonger, Jill

    2014-01-01

    A complex array of genetic factors regulates neuronal dendrite morphology. Epigenetic regulation of gene expression represents a plausible mechanism to control pathways responsible for specific dendritic arbor shapes. By studying the Drosophila dendritic arborization (da) neurons, we discovered a role of the double-bromodomain and extraterminal (BET) family proteins in regulating dendrite arbor complexity. A loss-of-function mutation in the single Drosophila BET protein encoded by female sterile 1 homeotic [fs(1)h] causes loss of fine, terminal dendritic branches. Moreover, fs(1)h is necessary for the induction of branching caused by a previously identified transcription factor, Cut (Ct), which regulates subtype-specific dendrite morphology. Finally, disrupting fs(1)h function impairs the mechanosensory response of class III da sensory neurons without compromising the expression of the ion channel NompC, which mediates the mechanosensitive response. Thus, our results identify a novel role for BET family proteins in regulating dendrite morphology and a possible separation of developmental pathways specifying neural cell morphology and ion channel expression. Since the BET proteins are known to bind acetylated histone tails, these results also suggest a role of epigenetic histone modifications and the “histone code,” in regulating dendrite morphology. PMID:25184680

  15. Double-bromo and extraterminal (BET) domain proteins regulate dendrite morphology and mechanosensory function.

    PubMed

    Bagley, Joshua A; Yan, Zhiqiang; Zhang, Wei; Wildonger, Jill; Jan, Lily Yeh; Jan, Yuh Nung

    2014-09-01

    A complex array of genetic factors regulates neuronal dendrite morphology. Epigenetic regulation of gene expression represents a plausible mechanism to control pathways responsible for specific dendritic arbor shapes. By studying the Drosophila dendritic arborization (da) neurons, we discovered a role of the double-bromodomain and extraterminal (BET) family proteins in regulating dendrite arbor complexity. A loss-of-function mutation in the single Drosophila BET protein encoded by female sterile 1 homeotic [fs(1)h] causes loss of fine, terminal dendritic branches. Moreover, fs(1)h is necessary for the induction of branching caused by a previously identified transcription factor, Cut (Ct), which regulates subtype-specific dendrite morphology. Finally, disrupting fs(1)h function impairs the mechanosensory response of class III da sensory neurons without compromising the expression of the ion channel NompC, which mediates the mechanosensitive response. Thus, our results identify a novel role for BET family proteins in regulating dendrite morphology and a possible separation of developmental pathways specifying neural cell morphology and ion channel expression. Since the BET proteins are known to bind acetylated histone tails, these results also suggest a role of epigenetic histone modifications and the "histone code," in regulating dendrite morphology. © 2014 Bagley et al.; Published by Cold Spring Harbor Laboratory Press.

  16. Small G proteins Rac1 and Ras regulate serine/threonine protein phosphatase 5 (PP5)·extracellular signal-regulated kinase (ERK) complexes involved in the feedback regulation of Raf1.

    PubMed

    Mazalouskas, Matthew D; Godoy-Ruiz, Raquel; Weber, David J; Zimmer, Danna B; Honkanen, Richard E; Wadzinski, Brian E

    2014-02-14

    Serine/threonine protein phosphatase 5 (PP5, PPP5C) is known to interact with the chaperonin heat shock protein 90 (HSP90) and is involved in the regulation of multiple cellular signaling cascades that control diverse cellular processes, such as cell growth, differentiation, proliferation, motility, and apoptosis. Here, we identify PP5 in stable complexes with extracellular signal-regulated kinases (ERKs). Studies using mutant proteins reveal that the formation of PP5·ERK1 and PP5·ERK2 complexes partially depends on HSP90 binding to PP5 but does not require PP5 or ERK1/2 activity. However, PP5 and ERK activity regulates the phosphorylation state of Raf1 kinase, an upstream activator of ERK signaling. Whereas expression of constitutively active Rac1 promotes the assembly of PP5·ERK1/2 complexes, acute activation of ERK1/2 fails to influence the phosphatase-kinase interaction. Introduction of oncogenic HRas (HRas(V12)) has no effect on PP5-ERK1 binding but selectively decreases the interaction of PP5 with ERK2, in a manner that is independent of PP5 and MAPK/ERK kinase (MEK) activity, yet paradoxically requires ERK2 activity. Additional studies conducted with oncogenic variants of KRas4B reveal that KRas(L61), but not KRas(V12), also decreases the PP5-ERK2 interaction. The expression of wild type HRas or KRas proteins fails to reduce PP5-ERK2 binding, indicating that the effect is specific to HRas(V12) and KRas(L61) gain-of-function mutations. These findings reveal a novel, differential responsiveness of PP5-ERK1 and PP5-ERK2 interactions to select oncogenic Ras variants and also support a role for PP5·ERK complexes in regulating the feedback phosphorylation of PP5-associated Raf1.

  17. Neurotization of the phrenic nerve with accessory nerve for high cervical spinal cord injury with respiratory distress: an anatomic study.

    PubMed

    Wang, Ce; Zhang, Ying; Nicholas, Tsai; Wu, Guoxin; Shi, Sheng; Bo, Yin; Wang, Xinwei; Zhou, Xuhui; Yuan, Wen

    2014-01-01

    High cervical spinal cord injury is associated with high morbidity and mortality. Traditional treatments carry various complications such as infection, pacemaker failure and undesirable movement. Thus, a secure surgical strategy with fewer complications analogous to physiological ventilation is still required. We hope to offer one potential method to decrease the complications and improve survival qualities of patients from the aspect of anatomy. The purpose of the study is to provide anatomic details on the accessory nerve and phrenic nerve for neurotization in patients with high spinal cord injuries. 38 cadavers (76 accessory and 76 phrenic nerves) were dissected in the study. The width, length and thickness of each accessory nerve and phrenic nerve above clavicle were measured. The distances from several landmarks on accessory nerve to the origin and the end of the phrenic nerve above clavicle were measured too. Then, the number of motor nerve fibers on different sections of the nerves was calculated using the technique of immunohistochemistry. The accessory nerves distal to its sternocleidomastoid muscular branches were 1.52 ± 0.32 mm ~1.54 ± 0.29 mm in width, 0.52 ± 0.18 mm ~ 0.56 ± 0.20mm in thickness and 9.52 ± 0.98 cm in length. And the phrenic nerves above clavicle were 1.44 ± 0.23 mm ~ 1.45 ± 0.24 mm in width, 0.47 ± 0.15 mm ~ 0.56 ± 0.25 mm in thickness and 6.48 ± 0.78 cm in length. The distance between the starting point of accessory nerve and phrenic nerve were 3.24 ± 1.17 cm, and the distance between the starting point of accessory nerve and the end of the phrenic nerve above clavicle were 8.72 ± 0.84 cm. The numbers of motor nerve fibers in accessory nerve were 1,038 ± 320~1,102 ± 216, before giving out the sternocleidomastoid muscular branches. The number of motor nerve fibers in the phrenic nerve was 911 ± 321~1,338 ± 467. The accessory nerve and the phrenic were similar in width, thickness and the number of motor nerve fibers. And

  18. RNA regulators responding to ribosomal protein S15 are frequent in sequence space

    PubMed Central

    Slinger, Betty L.; Meyer, Michelle M.

    2016-01-01

    There are several natural examples of distinct RNA structures that interact with the same ligand to regulate the expression of homologous genes in different organisms. One essential question regarding this phenomenon is whether such RNA regulators are the result of convergent or divergent evolution. Are the RNAs derived from some common ancestor and diverged to the point where we cannot identify the similarity, or have multiple solutions to the same biological problem arisen independently? A key variable in assessing these alternatives is how frequently such regulators arise within sequence space. Ribosomal protein S15 is autogenously regulated via an RNA regulator in many bacterial species; four apparently distinct regulators have been functionally validated in different bacterial phyla. Here, we explore how frequently such regulators arise within a partially randomized sequence population. We find many RNAs that interact specifically with ribosomal protein S15 from Geobacillus kaustophilus with biologically relevant dissociation constants. Furthermore, of the six sequences we characterize, four show regulatory activity in an Escherichia coli reporter assay. Subsequent footprinting and mutagenesis analysis indicates that protein binding proximal to regulatory features such as the Shine–Dalgarno sequence is sufficient to enable regulation, suggesting that regulation in response to S15 is relatively easily acquired. PMID:27580716

  19. 21 CFR 884.1600 - Transabdominal amnioscope (fetoscope) and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Transabdominal amnioscope (fetoscope) and accessories. 884.1600 Section 884.1600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...) Identification. A transabdominal amnioscope is a device designed to permit direct visual examination of the fetus...

  20. 21 CFR 878.4200 - Introduction/drainage catheter and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Introduction/drainage catheter and accessories. 878.4200 Section 878.4200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4200...