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Sample records for accessory protein vpu

  1. HIV-1 Accessory Proteins: Vpu and Vif

    PubMed Central

    Andrew, Amy; Strebel, Klaus

    2014-01-01

    HIV-1 Vif and Vpu are accessory factors involved in late stages of viral replication. Vif regulates viral infectivity by preventing virion incorporation of APOBEC3G and other members of the family of cytidine deaminases, while Vpu causes degradation of CD4 and promotes virus release by functionally inactivating the host factor BST-2. This chapter described techniques used for the characterization of Vif and Vpu and their functional interaction with host factors. Many of the techniques are, however, applicable to the functional analysis of other viral proteins. PMID:24158820

  2. Sequences in gibbon ape leukemia virus envelope that confer sensitivity to HIV-1 accessory protein Vpu.

    PubMed

    Janaka, Sanath Kumar; Lucas, Tiffany M; Johnson, Marc C

    2011-11-01

    HIV-1 efficiently forms pseudotyped particles with many gammaretrovirus glycoproteins, such as Friend murine leukemia virus (F-MLV) Env, but not with the related gibbon ape leukemia virus (GaLV) Env or with a chimeric F-MLV Env with a GaLV cytoplasmic tail domain (CTD). This incompatibility is modulated by the HIV-1 accessory protein Vpu. Because the GaLV Env CTD does not resemble tetherin or CD4, the well-studied targets of Vpu, we sought to characterize the modular sequence in the GaLV Env CTD required for this restriction in the presence of Vpu. Using a systematic mutagenesis scan, we determined that the motif that makes GaLV Env sensitive to Vpu is INxxIxxVKxxVxRxK. This region in the CTD of GaLV Env is predicted to form a helix. Mutations in the CTD that would break this helix abolish sensitivity to Vpu. Although many of these positions can be replaced with amino acids with similar biophysical properties without disrupting the Vpu sensitivity, the final lysine residue is required. This Vpu sensitivity sequence appears to be modular, as the unrelated Rous sarcoma virus (RSV) Env can be made Vpu sensitive by replacing its CTD with the GaLV Env CTD. In addition, F-MLV Env can be made Vpu sensitive by mutating two amino acids in its cytoplasmic tail to make it resemble more closely the Vpu sensitivity motif. Surprisingly, the core components of this Vpu sensitivity sequence are also present in the host surface protein CD4, which is also targeted by Vpu through its CTD.

  3. HIV-1 Vpu Accessory Protein Induces Caspase-mediated Cleavage of IRF3 Transcription Factor*

    PubMed Central

    Park, Sang Yoon; Waheed, Abdul A.; Zhang, Zai-Rong; Freed, Eric O.; Bonifacino, Juan S.

    2014-01-01

    Vpu is an accessory protein encoded by HIV-1 that interferes with multiple host-cell functions. Herein we report that expression of Vpu by transfection into 293T cells causes partial proteolytic cleavage of interferon regulatory factor 3 (IRF3), a key transcription factor in the innate anti-viral response. Vpu-induced IRF3 cleavage is mediated by caspases and occurs mainly at Asp-121. Cleavage produces a C-terminal fragment of ∼37 kDa that comprises the IRF dimerization and transactivation domains but lacks the DNA-binding domain. A similar cleavage is observed upon infection of the Jurkat T-cell line with vesicular stomatitis virus G glycoprotein (VSV-G)-pseudotyped HIV-1. Two other HIV-1 accessory proteins, Vif and Vpr, also contribute to the induction of IRF3 cleavage in both the transfection and the infection systems. The C-terminal IRF3 fragment interferes with the transcriptional activity of full-length IRF3. Cleavage of IRF3 under all of these conditions correlates with cleavage of poly(ADP-ribose) polymerase, an indicator of apoptosis. We conclude that Vpu contributes to the attenuation of the anti-viral response by partial inactivation of IRF3 while host cells undergo apoptosis. PMID:25352594

  4. The HIV-1 Vpu protein induces apoptosis in Drosophila via activation of JNK signaling.

    PubMed

    Marchal, Christelle; Vinatier, Gérald; Sanial, Matthieu; Plessis, Anne; Pret, Anne-Marie; Limbourg-Bouchon, Bernadette; Théodore, Laurent; Netter, Sophie

    2012-01-01

    The genome of the human immunodeficiency virus type 1 (HIV-1) encodes the canonical retroviral proteins, as well as additional accessory proteins that enhance the expression of viral genes, the infectivity of the virus and the production of virions. The accessory Viral Protein U (Vpu), in particular, enhances viral particle production, while also promoting apoptosis of HIV-infected human T lymphocytes. Some Vpu effects rely on its interaction with the ubiquitin-proteasome protein degradation system, but the mechanisms responsible for its pro-apoptotic effects in vivo are complex and remain largely to be elucidated.We took advantage of the Drosophila model to study the effects of Vpu activity in vivo. Expression of Vpu in the developing Drosophila wing provoked tissue loss due to caspase-dependent apoptosis. Moreover, Vpu induced expression of the pro-apoptotic gene reaper, known to down-regulate Inhibitor of Apoptosis Proteins (IAPs) which are caspase-antagonizing E3 ubiquitin ligases. Indeed, Vpu also reduced accumulation of Drosophila IAP1 (DIAP1). Though our results demonstrate a physical interaction between Vpu and the proteasome-addressing SLIMB/β-TrCP protein, as in mammals, both SLIMB/βTrCP-dependent and -independent Vpu effects were observed in the Drosophila wing. Lastly, the pro-apoptotic effect of Vpu in this tissue was abrogated upon inactivation of the c-Jun N-terminal Kinase (JNK) pathway. Our results in the fly thus provide the first functional evidence linking Vpu pro-apoptotic effects to activation of the conserved JNK pathway.

  5. The HIV-1 Vpu Protein Induces Apoptosis in Drosophila via Activation of JNK Signaling

    PubMed Central

    Marchal, Christelle; Vinatier, Gérald; Sanial, Matthieu; Plessis, Anne; Pret, Anne-Marie; Limbourg-Bouchon, Bernadette; Théodore, Laurent; Netter, Sophie

    2012-01-01

    The genome of the human immunodeficiency virus type 1 (HIV-1) encodes the canonical retroviral proteins, as well as additional accessory proteins that enhance the expression of viral genes, the infectivity of the virus and the production of virions. The accessory Viral Protein U (Vpu), in particular, enhances viral particle production, while also promoting apoptosis of HIV-infected human T lymphocytes. Some Vpu effects rely on its interaction with the ubiquitin–proteasome protein degradation system, but the mechanisms responsible for its pro-apoptotic effects in vivo are complex and remain largely to be elucidated. We took advantage of the Drosophila model to study the effects of Vpu activity in vivo. Expression of Vpu in the developing Drosophila wing provoked tissue loss due to caspase-dependent apoptosis. Moreover, Vpu induced expression of the pro-apoptotic gene reaper, known to down-regulate Inhibitor of Apoptosis Proteins (IAPs) which are caspase-antagonizing E3 ubiquitin ligases. Indeed, Vpu also reduced accumulation of Drosophila IAP1 (DIAP1). Though our results demonstrate a physical interaction between Vpu and the proteasome-addressing SLIMB/β-TrCP protein, as in mammals, both SLIMB/βTrCP-dependent and -independent Vpu effects were observed in the Drosophila wing. Lastly, the pro-apoptotic effect of Vpu in this tissue was abrogated upon inactivation of the c-Jun N-terminal Kinase (JNK) pathway. Our results in the fly thus provide the first functional evidence linking Vpu pro-apoptotic effects to activation of the conserved JNK pathway. PMID:22479597

  6. Accessories to the crime: recent advances in HIV accessory protein biology.

    PubMed

    Gramberg, Thomas; Sunseri, Nicole; Landau, Nathaniel R

    2009-02-01

    Recent advances in understanding the roles of the lentiviral accessory proteins have provided fascinating insight into the molecular biology of the virus and uncovered previously unappreciated innate immune mechanisms by which the host defends itself. HIV-1 and other lentiviruses have developed accessory proteins that counterattack the antiviral defenses in a sort of evolutionary battle. The virus is remarkably adept at co-opting cellular degradative pathways to destroy the protective proteins. This review focuses on recent advances in understanding three of the accessory proteins-virion infectivity factor (Vif), viral protein R (Vpr), and viral protein U (Vpu)-that target different restriction factors to ensure virus replication. These proteins may provide promising targets for the development of novel classes of antiretroviral drugs.

  7. Structural modeling of Vpu from HIV-1 based on solid-state NMR observables

    NASA Astrophysics Data System (ADS)

    Ahn, SeonJoo; Lim, GyuTae; Nam, Seungyoon; Lee, Jinhyuk

    2014-04-01

    Vpu is one of the accessory proteins of HIV-1, and is involved in viral particle release. Viral particle release is enhanced by two proposed functions of Vpu: (i) tetherin interaction and (ii) membrane polarization. Two Vpu functions in viral particle release are still controversial. Here, we investigated the proposed functions by extensive structural modeling of Vpu based on solid-state NMR (Nuclear Magnetic Resonance) observables. We found that Vpu can co-exist in two structural forms: left-handed and right-handed conformation. The co-existence of the two conformations provides a clue to reconcile the controversial issue of its two functions in virus particle release.

  8. Membrane protein assembly: two cytoplasmic phosphorylated serine sites of Vpu from HIV-1 affect oligomerization

    PubMed Central

    Chen, Chin-Pei; Lin, Meng-Han; Chan, Ya-Ting; Chen, Li-Chyong; Ma, Che; Fischer, Wolfgang B.

    2016-01-01

    Viral protein U (Vpu) encoded by human immunodeficiency virus type 1 (HIV-1) is a short integral membrane protein which is known to self-assemble within the lipid membrane and associate with host factors during the HIV-1 infectivity cycle. In this study, full-length Vpu (M group) from clone NL4-3 was over-expressed in human cells and purified in an oligomeric state. Various single and double mutations were constructed on its phosphorylation sites to mimic different degrees of phosphorylation. Size exclusion chromatography of wild-type Vpu and mutants indicated that the smallest assembly unit of Vpu was a dimer and over time Vpu formed higher oligomers. The rate of oligomerization increased when (i) the degree of phosphorylation at serines 52 and 56 was decreased and (ii) when the ionic strength was increased indicating that the cytoplasmic domain of Vpu affects oligomerization. Coarse-grained molecular dynamic simulations with models of wild-type and mutant Vpu in a hydrated lipid bilayer supported the experimental data in demonstrating that, in addition to a previously known role in downregulation of host factors, the phosphorylation sites of Vpu also modulate oligomerization. PMID:27353136

  9. In COS cells Vpu can both stabilize tetherin expression and counteract its antiviral activity.

    PubMed

    Waheed, Abdul A; Kuruppu, Nishani D; Felton, Kathryn L; D'Souza, Darren; Freed, Eric O

    2014-01-01

    The interferon-inducible cellular protein tetherin (CD317/BST-2) inhibits the release of a broad range of enveloped viruses. The HIV-1 accessory protein Vpu enhances virus particle release by counteracting this host restriction factor. While the antagonism of human tetherin by Vpu has been associated with both proteasomal and lysosomal degradation, the link between Vpu-mediated tetherin degradation and the ability of Vpu to counteract the antiviral activity of tetherin remains poorly understood. Here, we show that human tetherin is expressed at low levels in African green monkey kidney (COS) cells. However, Vpu markedly increases tetherin expression in this cell line, apparently by sequestering it in an internal compartment that bears lysosomal markers. This stabilization of tetherin by Vpu requires the transmembrane sequence of human tetherin. Although Vpu stabilizes human tetherin in COS cells, it still counteracts the ability of tetherin to suppress virus release. The enhancement of virus release by Vpu in COS cells is associated with a modest reduction in cell-surface tetherin expression, even though the overall expression of tetherin is higher in the presence of Vpu. This study demonstrates that COS cells provide a model system in which Vpu-mediated enhancement of HIV-1 release is uncoupled from Vpu-mediated tetherin degradation.

  10. Vpu downmodulates two distinct targets, tetherin and gibbon ape leukemia virus envelope, through shared features in the Vpu cytoplasmic tail.

    PubMed

    Lucas, Tiffany M; Janaka, Sanath K; Stephens, Edward B; Johnson, Marc C

    2012-01-01

    During human immunodeficiency virus-1 (HIV-1) assembly, the host proteins CD4 (the HIV-1 receptor) and tetherin (an interferon stimulated anti-viral protein) both reduce viral fitness. The HIV-1 accessory gene Vpu counteracts both of these proteins, but it is thought to do so through two distinct mechanisms. Modulation of CD4 likely occurs through proteasomal degradation from the endoplasmic reticulum. The exact mechanism of tetherin modulation is less clear, with possible roles for degradation and alteration of protein transport to the plasma membrane. Most investigations of Vpu function have used different assays for CD4 and tetherin. In addition, many of these investigations used exogenously expressed Vpu, which could result in variable expression levels. Thus, few studies have investigated these two Vpu functions in parallel assays, making direct comparisons difficult. Here, we present results from a rapid assay used to simultaneously investigate Vpu-targeting of both tetherin and a viral glycoprotein, gibbon ape leukemia virus envelope (GaLV Env). We previously reported that Vpu modulates GaLV Env and prevents its incorporation into HIV-1 particles through a recognition motif similar to that found in CD4. Using this assay, we performed a comprehensive mutagenic scan of Vpu in its native proviral context to identify features required for both types of activity. We observed considerable overlap in the Vpu sequences required to modulate tetherin and GaLV Env. We found that features in the cytoplasmic tail of Vpu, specifically within the cytoplasmic tail hinge region, were required for modulation of both tetherin and GaLV Env. Interestingly, these same regions features have been determined to be critical for CD4 downmodulation. We also observed a role for the transmembrane domain in the restriction of tetherin, as previously reported, but not of GaLV Env. We propose that Vpu may target both proteins in a mechanistically similar manner, albeit in different cellular

  11. Some human immunodeficiency virus type 1 Vpu proteins are able to antagonize macaque BST-2 in vitro and in vivo: Vpu-negative simian-human immunodeficiency viruses are attenuated in vivo.

    PubMed

    Shingai, Masashi; Yoshida, Takeshi; Martin, Malcolm A; Strebel, Klaus

    2011-10-01

    Human immunodeficiency virus type 1 (HIV-1) Vpu enhances the release of viral particles from infected cells by targeting BST-2/tetherin, a cellular protein inhibiting virus release. The widely used HIV-1(NL4-3) Vpu functionally inactivates human BST-2 but not murine or monkey BST-2, leading to the notion that Vpu antagonism is species specific. Here we investigated the properties of the CXCR4-tropic simian-human immunodeficiency virus DH12 (SHIV(DH12)) and the CCR5-tropic SHIV(AD8), each of which carries vpu genes derived from different primary HIV-1 isolates. We found that virion release from infected rhesus peripheral blood mononuclear cells was enhanced to various degrees by the Vpu present in both SHIVs. Transfer of the SHIV(DH12) Vpu transmembrane domain to the HIV-1(NL4-3) Vpu conferred antagonizing activity against macaque BST-2. Inactivation of the SHIV(DH12) and SHIV(AD8) vpu genes impaired virus replication in 6 of 8 inoculated rhesus macaques, resulting in lower plasma viral RNA loads, slower losses of CD4(+) T cells, and delayed disease progression. The expanded host range of the SHIV(DH12) Vpu was not due to adaptation during passage in macaques but was an intrinsic property of the parental HIV-1(DH12) Vpu protein. These results demonstrate that the species-specific inhibition of BST-2 by HIV-1(NL4-3) Vpu is not characteristic of all HIV-1 Vpu proteins; some HIV-1 isolates encode a Vpu with a broader host range.

  12. Ion Channel Activity of Vpu Proteins Is Conserved throughout Evolution of HIV-1 and SIV

    PubMed Central

    Greiner, Timo; Bolduan, Sebastian; Hertel, Brigitte; Groß, Christine; Hamacher, Kay; Schubert, Ulrich; Moroni, Anna; Thiel, Gerhard

    2016-01-01

    The human immunodeficiency virus type 1 (HIV-1) protein Vpu is encoded exclusively by HIV-1 and related simian immunodeficiency viruses (SIVs). The transmembrane domain of the protein has dual functions: it counteracts the human restriction factor tetherin and forms a cation channel. Since these two functions are causally unrelated it remains unclear whether the channel activity has any relevance for viral release and replication. Here we examine structure and function correlates of different Vpu homologs from HIV-1 and SIV to understand if ion channel activity is an evolutionary conserved property of Vpu proteins. An electrophysiological testing of Vpus from different HIV-1 groups (N and P) and SIVs from chimpanzees (SIVcpz), and greater spot-nosed monkeys (SIVgsn) showed that they all generate channel activity in HEK293T cells. This implies a robust and evolutionary conserved channel activity and suggests that cation conductance may also have a conserved functional significance. PMID:27916968

  13. Bacterial expression, correct membrane targeting and functional folding of the HIV-1 membrane protein Vpu using a periplasmic signal peptide.

    PubMed

    Deb, Arpan; Johnson, William A; Kline, Alexander P; Scott, Boston J; Meador, Lydia R; Srinivas, Dustin; Martin-Garcia, Jose M; Dörner, Katerina; Borges, Chad R; Misra, Rajeev; Hogue, Brenda G; Fromme, Petra; Mor, Tsafrir S

    2017-01-01

    Viral protein U (Vpu) is a type-III integral membrane protein encoded by Human Immunodeficiency Virus-1 (HIV- 1). It is expressed in infected host cells and plays several roles in viral progeny escape from infected cells, including down-regulation of CD4 receptors. But key structure/function questions remain regarding the mechanisms by which the Vpu protein contributes to HIV-1 pathogenesis. Here we describe expression of Vpu in bacteria, its purification and characterization. We report the successful expression of PelB-Vpu in Escherichia coli using the leader peptide pectate lyase B (PelB) from Erwinia carotovora. The protein was detergent extractable and could be isolated in a very pure form. We demonstrate that the PelB signal peptide successfully targets Vpu to the cell membranes and inserts it as a type I membrane protein. PelB-Vpu was biophysically characterized by circular dichroism and dynamic light scattering experiments and was shown to be an excellent candidate for elucidating structural models.

  14. Bacterial expression, correct membrane targeting and functional folding of the HIV-1 membrane protein Vpu using a periplasmic signal peptide

    PubMed Central

    Deb, Arpan; Johnson, William A.; Kline, Alexander P.; Scott, Boston J.; Meador, Lydia R.; Srinivas, Dustin; Martin-Garcia, Jose M.; Dörner, Katerina; Borges, Chad R.; Misra, Rajeev; Hogue, Brenda G.; Fromme, Petra

    2017-01-01

    Viral protein U (Vpu) is a type-III integral membrane protein encoded by Human Immunodeficiency Virus-1 (HIV- 1). It is expressed in infected host cells and plays several roles in viral progeny escape from infected cells, including down-regulation of CD4 receptors. But key structure/function questions remain regarding the mechanisms by which the Vpu protein contributes to HIV-1 pathogenesis. Here we describe expression of Vpu in bacteria, its purification and characterization. We report the successful expression of PelB-Vpu in Escherichia coli using the leader peptide pectate lyase B (PelB) from Erwinia carotovora. The protein was detergent extractable and could be isolated in a very pure form. We demonstrate that the PelB signal peptide successfully targets Vpu to the cell membranes and inserts it as a type I membrane protein. PelB-Vpu was biophysically characterized by circular dichroism and dynamic light scattering experiments and was shown to be an excellent candidate for elucidating structural models. PMID:28225803

  15. Putative alpha-helical structures in the human immunodeficiency virus type 1 Vpu protein and CD4 are involved in binding and degradation of the CD4 molecule.

    PubMed Central

    Tiganos, E; Yao, X J; Friborg, J; Daniel, N; Cohen, E A

    1997-01-01

    The human immunodeficiency virus type 1 (HIV-1) vpu gene encodes a 16-kDa class I integral membrane phosphoprotein with an N-terminal membrane-spanning region and a C-terminal cytoplasmic domain. In the cytoplasmic domain, two amphipathic alpha-helices joined by a flexible turn containing two phosphoacceptor sites have been predicted. Previous studies have shown that Vpu downregulates CD4 molecules by inducing their specific degradation in the endoplasmic reticulum. Phosphorylation of serine residues 52 and 56, present within the cytoplasmic domain of the Vpu protein, has been shown to be essential to this Vpu function. However, the contribution of these two phosphoacceptor sites in the mechanism of CD4 degradation remains undefined. Interestingly, a specific interaction between Vpu and CD4 was recently demonstrated in coimmunoprecipitation experiments. Binding of Vpu was shown to be necessary but not sufficient to mediate CD4 degradation, indicating that interaction between Vpu and CD4 represents an early step critical in triggering a process leading to CD4 degradation. To delineate the sequence(s) and/or structural determinant(s) involved in this Vpu-CD4 interaction and in the Vpu-mediated CD4 degradation, we performed a mutational analysis of the cytoplasmic domain of CD4 and Vpu. Coimmunoprecipitation experiments reveal that disruption of the putative alpha-helical structure in the membrane-proximal cytoplasmic domain of CD4 affects the binding to Vpu, suggesting that this structure may act as an interface for the CD4-Vpu interaction that mediates CD4 degradation. Vpu proteins containing mutations in either or both of the phosphoacceptor sites (Ser52 or/and Ser56) were inactive in regard to CD4 degradation yet retained the capacity to interact with the cytoplasmic domain of CD4. In an attempt to define the minimal region responsible for this interaction, we tested a panel of mutations which were designed to affect the integrity of the putative alpha

  16. Species-Specific Activity of HIV-1 Vpu and Positive Selection of Tetherin Transmembrane Domain Variants

    PubMed Central

    McNatt, Matthew W.; Zang, Trinity; Hatziioannou, Theodora; Bartlett, Mackenzie; Fofana, Ismael Ben; Johnson, Welkin E.; Neil, Stuart J. D.; Bieniasz, Paul D.

    2009-01-01

    Tetherin/BST-2/CD317 is a recently identified antiviral protein that blocks the release of nascent retrovirus, and other virus, particles from infected cells. An HIV-1 accessory protein, Vpu, acts as an antagonist of tetherin. Here, we show that positive selection is evident in primate tetherin sequences and that HIV-1 Vpu appears to have specifically adapted to antagonize variants of tetherin found in humans and chimpanzees. Tetherin variants found in rhesus macaques (rh), African green monkeys (agm) and mice were able to inhibit HIV-1 particle release, but were resistant to antagonism by HIV-1 Vpu. Notably, reciprocal exchange of transmembrane domains between human and monkey tetherins conferred sensitivity and resistance to Vpu, identifying this protein domain as a critical determinant of Vpu function. Indeed, differences between hu-tetherin and rh-tetherin at several positions in the transmembrane domain affected sensitivity to antagonism by Vpu. Two alterations in the hu-tetherin transmembrane domain, that correspond to differences found in rh- and agm-tetherin proteins, were sufficient to render hu-tetherin completely resistant to HIV-1 Vpu. Interestingly, transmembrane and cytoplasmic domain sequences in primate tetherins exhibit variation at numerous codons that is likely the result of positive selection, and some of these changes coincide with determinants of HIV-1 Vpu sensitivity. Overall, these data indicate that tetherin could impose a barrier to viral zoonosis as a consequence of positive selection that has been driven by ancient viral antagonists, and that the HIV-1 Vpu protein has specialized to target the transmembrane domains found in human/chimpanzee tetherin proteins. PMID:19214216

  17. Species-specific activity of HIV-1 Vpu and positive selection of tetherin transmembrane domain variants.

    PubMed

    McNatt, Matthew W; Zang, Trinity; Hatziioannou, Theodora; Bartlett, Mackenzie; Fofana, Ismael Ben; Johnson, Welkin E; Neil, Stuart J D; Bieniasz, Paul D

    2009-02-01

    Tetherin/BST-2/CD317 is a recently identified antiviral protein that blocks the release of nascent retrovirus, and other virus, particles from infected cells. An HIV-1 accessory protein, Vpu, acts as an antagonist of tetherin. Here, we show that positive selection is evident in primate tetherin sequences and that HIV-1 Vpu appears to have specifically adapted to antagonize variants of tetherin found in humans and chimpanzees. Tetherin variants found in rhesus macaques (rh), African green monkeys (agm) and mice were able to inhibit HIV-1 particle release, but were resistant to antagonism by HIV-1 Vpu. Notably, reciprocal exchange of transmembrane domains between human and monkey tetherins conferred sensitivity and resistance to Vpu, identifying this protein domain as a critical determinant of Vpu function. Indeed, differences between hu-tetherin and rh-tetherin at several positions in the transmembrane domain affected sensitivity to antagonism by Vpu. Two alterations in the hu-tetherin transmembrane domain, that correspond to differences found in rh- and agm-tetherin proteins, were sufficient to render hu-tetherin completely resistant to HIV-1 Vpu. Interestingly, transmembrane and cytoplasmic domain sequences in primate tetherins exhibit variation at numerous codons that is likely the result of positive selection, and some of these changes coincide with determinants of HIV-1 Vpu sensitivity. Overall, these data indicate that tetherin could impose a barrier to viral zoonosis as a consequence of positive selection that has been driven by ancient viral antagonists, and that the HIV-1 Vpu protein has specialized to target the transmembrane domains found in human/chimpanzee tetherin proteins.

  18. Characterization of the interface of the bone marrow stromal cell antigen 2-Vpu protein complex via computational chemistry.

    PubMed

    Zhou, Jinming; Zhang, Zhixin; Mi, Zeyun; Wang, Xin; Zhang, Quan; Li, Xiaoyu; Liang, Chen; Cen, Shan

    2012-02-14

    Bone marrow stromal cell antigen 2 (BST-2) inhibits the release of enveloped viruses from the cell surface. Various viral counter measures have been discovered, which allow viruses to escape BST-2 restriction. Human immunodeficiency virus type 1 (HIV-1) encodes viral protein U (Vpu) that interacts with BST-2 through their transmembrane domains and causes the downregulation of cell surface BST-2. In this study, we used a computer modeling method to establish a molecular model to investigate the binding interface of the transmembrane domains of BST-2 and Vpu. The model predicts that the interface is composed of Vpu residues I6, A10, A14, A18, V25, and W22 and BST-2 residues L23, I26, V30, I34, V35, L41, I42, and T45. Introduction of mutations that have been previously reported to disrupt the Vpu-BST-2 interaction led to a calculated higher binding free energy (MMGBSA), which supports our molecular model. A pharmacophore was also generated on the basis of this model. Our results provide a precise model that predicts the detailed interaction occurring between the transmembrane domains of Vpu and BST-2 and should facilitate the design of anti-HIV agents that are able to disrupt this interaction.

  19. Pseudotyping incompatibility between HIV-1 and gibbon ape leukemia virus Env is modulated by Vpu.

    PubMed

    Lucas, Tiffany M; Lyddon, Terri D; Cannon, Paula M; Johnson, Marc C

    2010-03-01

    The Env protein from gibbon ape leukemia virus (GaLV) has been shown to be incompatible with human immunodeficiency virus type 1 (HIV-1) in the production of infectious pseudotyped particles. This incompatibility has been mapped to the C-terminal cytoplasmic tail of GaLV Env. Surprisingly, we found that the HIV-1 accessory protein Vpu modulates this incompatibility. The infectivity of HIV-1 pseudotyped with murine leukemia virus (MLV) Env was not affected by Vpu. However, the infectivity of HIV-1 pseudotyped with an MLV Env with the cytoplasmic tail from GaLV Env (MLV/GaLV Env) was restricted 50- to 100-fold by Vpu. A Vpu mutant containing a scrambled membrane-spanning domain, Vpu(RD), was still able to restrict MLV/GaLV Env, but mutation of the serine residues at positions 52 and 56 completely alleviated the restriction. Loss of infectivity appeared to be caused by reduced MLV/GaLV Env incorporation into viral particles. The mechanism of this downmodulation appears to be distinct from Vpu-mediated CD4 downmodulation because Vpu-expressing cells that failed to produce infectious HIV-1 particles nonetheless continued to display robust surface MLV/GaLV Env expression. In addition, if MLV and HIV-1 were simultaneously introduced into the same cells, only the HIV-1 particle infectivity was restricted by Vpu. Collectively, these data suggest that Vpu modulates the cellular distribution of MLV/GaLV Env, preventing its recruitment to HIV-1 budding sites.

  20. A Naturally Occurring rev1-vpu Fusion Gene Does Not Confer a Fitness Advantage to HIV-1

    PubMed Central

    Langer, Simon M.; Hopfensperger, Kristina; Iyer, Shilpa S.; Kreider, Edward F.; Learn, Gerald H.; Lee, Lan-Hui; Hahn, Beatrice H.; Sauter, Daniel

    2015-01-01

    Background Pandemic strains of HIV-1 (group M) encode a total of nine structural (gag, pol, env), regulatory (rev, tat) and accessory (vif, vpr, vpu, nef) genes. However, some subtype A and C viruses exhibit an unusual gene arrangement in which the first exon of rev (rev1) and the vpu gene are placed in the same open reading frame. Although this rev1-vpu gene fusion is present in a considerable fraction of HIV-1 strains, its functional significance is unknown. Results Examining infectious molecular clones (IMCs) of HIV-1 that encode the rev1-vpu polymorphism, we show that a fusion protein is expressed in infected cells. Due to the splicing pattern of viral mRNA, however, these same IMCs also express a regular Vpu protein, which is produced at much higher levels. To investigate the function of the fusion gene, we characterized isogenic IMC pairs differing only in their ability to express a Rev1-Vpu protein. Analysis in transfected HEK293T and infected CD4+ T cells showed that all of these viruses were equally active in known Vpu functions, such as down-modulation of CD4 or counteraction of tetherin. Furthermore, the polymorphism did not affect Vpu-mediated inhibition of NF-кB activation or Rev-dependent nuclear export of incompletely spliced viral mRNAs. There was also no evidence for enhanced replication of Rev1-Vpu expressing viruses in primary PBMCs or ex vivo infected human lymphoid tissues. Finally, the frequency of HIV-1 quasispecies members that encoded a rev1-vpu fusion gene did not change in HIV-1 infected individuals over time. Conclusions Expression of a rev1-vpu fusion gene does not affect regular Rev and Vpu functions or alter HIV-1 replication in primary target cells. Since there is no evidence for increased replication fitness of rev1-vpu encoding viruses, this polymorphism likely emerged in the context of other mutations within and/or outside the rev1-vpu intergenic region, and may have a neutral phenotype. PMID:26554585

  1. HIV-1 encoded virus protein U (Vpu) solution structure of the 41-62 hydrophilic region containing the phosphorylated sites Ser52 and Ser56.

    PubMed

    Coadou, Gaël; Evrard-Todeschi, Nathalie; Gharbi-Benarous, Josyane; Benarous, Richard; Girault, Jean Pierre

    2002-03-08

    Degradation of the HIV receptor CD4 by the proteasome, mediated by the HIV-1 protein Vpu, is crucial for the release of fully infectious virions. To promote CD4 degradation Vpu has to be phosphorylated on a motif DSGXXS, which is conserved in several signalling proteins known to be degraded by the proteasome upon phosphorylation. Such phosphorylation is required for the interaction of Vpu with the ubiquitin ligase SCF-beta-TrCP that triggers CD4 degradation by the proteasome. In the present work, we used two peptides of 22 amino acids between residues 41 and 62 of Vpu. Vpu41-62 was predicted to form an alpha-helix-flexible-alpha-helix including the phosphorylation motif DS52GNES56 and Vpu_P41-62 was phosphorylated at the two sites Ser52 and Ser56. We analysed the conformational change induced by the phosphorylation of this peptide on the residues Ser52 and Ser56. Homo- and heteronuclear NMR techniques were used to assess the structural influence of phosphorylation. The spectra of the free peptides, Vpu_P41-62 and Vpu41-62, in both H2O (at pH 3.5 and 7.2) and a 1:1 mixture of H2O and trifluoroethanol were completely assigned by a combined application of several two-dimensional proton NMR methods. Analysis of the short- and medium-range NOE connectivities and of the secondary chemical shifts indicated that the peptide segment (42-49) shows a less well-defined helix propensity. The Vpu_P41-62 domain of residues 50-62 forms a loop with the phosphate group pointing away, a short beta-strand and a flexible extended 'tail' of residues 60-62. Residues 50-60 exhibit alpha-proton NMR secondary chemical shift changes from random coil toward more beta-like structure with the combined (temperature, solvent and pH) NMR and molecular calculation experiments. Differences in this molecular region 50-62 suggest that conformational changes of Vpu_P play an important role in Vpu_P-induced degradation of CD4 molecules.

  2. Accessory proteins for heterotrimeric G-proteins in the kidney

    PubMed Central

    Park, Frank

    2015-01-01

    Heterotrimeric G-proteins play a fundamentally important role in regulating signal transduction pathways in the kidney. Accessory proteins are being identified as direct binding partners for heterotrimeric G-protein α or βγ subunits to promote more diverse mechanisms by which G-protein signaling is controlled. In some instances, accessory proteins can modulate the signaling magnitude, localization, and duration following the activation of cell membrane-associated receptors. Alternatively, accessory proteins complexed with their G-protein α or βγ subunits can promote non-canonical models of signaling activity within the cell. In this review, we will highlight the expression profile, localization and functional importance of these newly identified accessory proteins to control the function of select G-protein subunits under normal and various disease conditions observed in the kidney. PMID:26300785

  3. Expression of HIV-1 Vpu leads to loss of the viral restriction factor CD317/Tetherin from lipid rafts and its enhanced lysosomal degradation.

    PubMed

    Rollason, Ruth; Dunstan, Katie; Billcliff, Peter G; Bishop, Paul; Gleeson, Paul; Wise, Helen; Digard, Paul; Banting, George

    2013-01-01

    CD317/tetherin (aka BST2 or HM1.24 antigen) is an interferon inducible membrane protein present in regions of the lipid bilayer enriched in sphingolipids and cholesterol (often termed lipid rafts). It has been implicated in an eclectic mix of cellular processes including, most notably, the retention of fully formed viral particles at the surface of cells infected with HIV and other enveloped viruses. Expression of the HIV viral accessory protein Vpu has been shown to lead to intracellular sequestration and degradation of tetherin, thereby counteracting the inhibition of viral release. There is evidence that tetherin interacts directly with Vpu, but it remains unclear where in the cell this interaction occurs or if Vpu expression affects the lipid raft localisation of tetherin. We have addressed these points using biochemical and cell imaging approaches focused on endogenous rather than ectopically over-expressed tetherin. We find i) no evidence for an interaction between Vpu and endogenous tetherin at the cell surface, ii) the vast majority of endogenous tetherin that is at the cell surface in control cells is in lipid rafts, iii) internalised tetherin is present in non-raft fractions, iv) expression of Vpu in cells expressing endogenous tetherin leads to the loss of tetherin from lipid rafts, v) internalised tetherin enters early endosomes, and late endosomes, in both control cells and cells expressing Vpu, but the proportion of tetherin molecules destined for degradation rather than recycling is increased in cells expressing Vpu vi) lysosomes are the primary site for degradation of endogenous tetherin in cells expressing Vpu. Our studies underlie the importance of studying endogenous tetherin and let us propose a model in which Vpu intercepts newly internalised tetherin and diverts it for lysosomal destruction rather than recycling to the cell surface.

  4. A cytoplasmic tail determinant in HIV-1 Vpu mediates targeting of tetherin for endosomal degradation and counteracts interferon-induced restriction.

    PubMed

    Kueck, Tonya; Neil, Stuart J D

    2012-01-01

    The HIV-1 accessory protein Vpu counteracts tetherin (BST-2/CD317) by preventing its incorporation into virions, reducing its surface expression, and ultimately promoting its degradation. Here we characterize a putative trafficking motif, EXXXLV, in the second alpha helix of the subtype-B Vpu cytoplasmic tail as being required for efficient tetherin antagonism. Mutation of this motif prevents ESCRT-dependent degradation of tetherin/Vpu complexes, tetherin cell surface downregulation, but not its physical interaction with Vpu. Importantly, this motif is required for efficient cell-free virion release from CD4+ T cells, particularly after their exposure to type-1 interferon, indicating that the ability to reduce surface tetherin levels and promote its degradation is important to counteract restriction under conditions that the virus likely encounters in vivo. Vpu EXXXLV mutants accumulate with tetherin at the cell surface and in endosomal compartments, but retain the ability to bind both β-TrCP2 and HRS, indicating that this motif is required for a post-binding trafficking event that commits tetherin for ESCRT-dependent degradation and prevents its transit to the plasma membrane and viral budding zones. We further found that while Vpu function is dependent on clathrin, and the entire second alpha helix of the Vpu tail can be functionally complemented by a clathrin adaptor binding peptide derived from HIV-1 Nef, none of the canonical clathrin adaptors nor retromer are required for this process. Finally we show that residual activity of Vpu EXXXLV mutants requires an intact endocytic motif in tetherin, suggesting that physical association of Vpu with tetherin during its recycling may be sufficient to compromise tetherin activity to some degree.

  5. Simian-Human immunodeficiency viruses expressing chimeric subtype B/C Vpu proteins demonstrate the importance of the amino terminal and transmembrane domains in the rate of CD4(+) T cell loss in macaques.

    PubMed

    Ruiz, Autumn; Schmitt, Kimberly; Culley, Nathan; Stephens, Edward B

    2013-01-20

    Previously, we reported that simian-human immunodeficiency viruses expressing either the lab adapted subtype B (SHIV(KU-1bMC33)) or subtype C (SHIV(SCVpu)) Vpu proteins of human immunodeficiency virus type 1 (HIV-1) had different rates of CD4(+) T cell loss following inoculation into macaques. In this study, we have generated SHIVs that express either the subtype B or subtype C N-terminal (NTD) and transmembrane (TMD) domains and the opposing cytoplasmic domain (SHIV(VpuBC), SHIV(VpuCB)). In culture systems, SHIV(VpuBC) replicated faster than SHIV(VpuCB) while both proteins exhibited similar ability to down-modulate CD4 surface expression. Following inoculation into macaques, SHIV(VpuBC) resulted in rapid CD4(+) T cell loss similar to the parental SHIV(KU-1bMC33), while the rate of CD4(+) T cell loss in those inoculated with SHIV(VpuCB) was intermediate of SHIV(SCVpu) and SHIV(KU-1bMC33). These results emphasize the importance of the Vpu NTD/TMD region in the rate of CD4(+) T cell loss in the pathogenic X4 SHIV/macaque model.

  6. Manipulation of immunometabolism by HIV-accessories to the crime?

    PubMed

    Matheson, Nicholas J; Greenwood, Edward Jd; Lehner, Paul J

    2016-08-01

    Evolutionary pressure has produced an 'arms race' between cellular restriction factors (limiting viral replication) and viral proteins (overcoming host restriction). The host factors SAMHD1 and SLFN1 patrol metabolic bottlenecks required for HIV replication. Conversely, the HIV accessory proteins Vpx, Vpu and Nef manipulate cellular metabolism to enable viral replication. Recent work identifying Vpu-mediated downregulation of the alanine transporter SNAT1 and Nef-mediated downregulation of the serine carriers SERINC3/5 has uncovered the importance of HIV manipulation of the amino acid supply. Interference with CD4(+) T-cell amino acid metabolism suggests a novel paradigm of viral immunomodulation, and signposts fundamental aspects of lymphocyte biology.

  7. CD4 Glycoprotein Degradation Induced by Human Immunodeficiency Virus Type 1 Vpu Protein Requires the Function of Proteasomes and the Ubiquitin-Conjugating Pathway

    PubMed Central

    Schubert, Ulrich; Antón, Luis C.; Bačík, Igor; Cox, Josephine H.; Bour, Stéphane; Bennink, Jack R.; Orlowski, Marian; Strebel, Klaus; Yewdell, Jonathan W.

    1998-01-01

    The human immunodeficiency virus type 1 (HIV-1) vpu gene encodes a type I anchored integral membrane phosphoprotein with two independent functions. First, it regulates virus release from a post-endoplasmic reticulum (ER) compartment by an ion channel activity mediated by its transmembrane anchor. Second, it induces the selective down regulation of host cell receptor proteins (CD4 and major histocompatibility complex class I molecules) in a process involving its phosphorylated cytoplasmic tail. In the present work, we show that the Vpu-induced proteolysis of nascent CD4 can be completely blocked by peptide aldehydes that act as competitive inhibitors of proteasome function and also by lactacystin, which blocks proteasome activity by covalently binding to the catalytic β subunits of proteasomes. The sensitivity of Vpu-induced CD4 degradation to proteasome inhibitors paralleled the inhibition of proteasome degradation of a model ubiquitinated substrate. Characterization of CD4-associated oligosaccharides indicated that CD4 rescued from Vpu-induced degradation by proteasome inhibitors is exported from the ER to the Golgi complex. This finding suggests that retranslocation of CD4 from the ER to the cytosol may be coupled to its proteasomal degradation. CD4 degradation mediated by Vpu does not require the ER chaperone calnexin and is dependent on an intact ubiquitin-conjugating system. This was demonstrated by inhibition of CD4 degradation (i) in cells expressing a thermally inactivated form of the ubiquitin-activating enzyme E1 or (ii) following expression of a mutant form of ubiquitin (Lys48 mutated to Arg48) known to compromise ubiquitin targeting by interfering with the formation of polyubiquitin complexes. CD4 degradation was also prevented by altering the four Lys residues in its cytosolic domain to Arg, suggesting a role for ubiquitination of one or more of these residues in the process of degradation. The results clearly demonstrate a role for the cytosolic

  8. The expression of HIV-1 Vpu in monocytes causes increased secretion of TGF-β that activates profibrogenic genes in hepatic stellate cells.

    PubMed

    Patel, Paresh; Khan, Nabab; Rani, Manjusha; Gupta, Deepti; Jameel, Shahid

    2014-01-01

    There is faster progression to fibrosis in persons with liver injury who are also infected with HIV. Other reports have suggested that HIV can directly infect and activate stellate cells, and the viral Tat and gp160 proteins also induce profibrogenic factors from peripheral blood mononuclear cells (PBMCs). We tested the role of HIV-1 Vpu accessory protein in promoting profibrogenic activation of hepatic stellate cells. Human stellate LX2 cells were cocultured with human monocytic U937 cells stably expressing the Vpu protein or latently infected U1 cells knocked down for Vpu expression, LX2 cells were also cultured with the supernatants from these cells. The expression of profibrogenic markers was evaluated in LX2 cells usingquantitative reverse transcription polymerase chain reaction (qRT-PCR),western blotting, immunofluorescence,flow cytometry and ELISA were used to confirm and quantitate protein expression. Monocytic cells expressing Vpu increased the expression of profibrogenic markers in LX2 cells. The culture supernatants of these cells contained increased levels of transforming growth factor beta (TGF-β), which correlated with increased activity of the AP-1 transcription factor. Antibodies against TGF-β or a TGF-β receptor inhibitor (SB431452) reversed Vpu-mediated profibrogenic activation of LX2 cells, suggesting that TGF-β mediated these effects. The cytokine macrophage migration inhibitory factor (MIF) attenuated Vpu-mediated TGF-β secretion and profibrogenic effects on LX2 cells. Besides its other roles in pathogenesis, Vpu is likely to contribute to hepatic fibrosis through this hitherto unknown mechanism.

  9. Functional conservation and coherence of HIV-1 subtype A Vpu alleles

    PubMed Central

    Romani, Bizhan; Kavyanifard, Amirarsalan; Allahbakhshi, Elham

    2017-01-01

    Functional studies of HIV-1 proteins are normally conducted using lab adapted strains of HIV-1. The extent of those functions in clinical strains is sometimes unknown. In this study, we amplified and sequenced HIV-1 Vpu from 10 Iranian patients infected with HIV-1. Phylogenetic analysis indicated that the Vpu alleles were closely related to the CRF35_AD from Iran and subtype A Vpu. We addressed some of the well-established functions of the HIV-1 Vpu, as well as some of its recently reported functions. Ability of the clinical strains of subtype A Vpu alleles for downregulation of CD4 was similar to that of the lab adapted NL4.3 Vpu. Majority of the subtype A Vpu alleles performed stronger than NL4.3 Vpu for downregulation of SNAT1. The Vpu alleles differentially induced downregulation of HLA-C, ranging from no effect to 88% downregulation of surface HLA-C. Downregulation of tetherin and enhancement of virus release was similar for the subtype A Vpu alleles and NL4.3. Subtype A Vpu alleles were more potent when compared with NL4.3 for inhibition of NF-κB activation. Our study shows that subtype A Vpu alleles exert the classical functions of HIV-1 Vpu. PMID:28317943

  10. Functional conservation and coherence of HIV-1 subtype A Vpu alleles.

    PubMed

    Romani, Bizhan; Kavyanifard, Amirarsalan; Allahbakhshi, Elham

    2017-12-01

    Functional studies of HIV-1 proteins are normally conducted using lab adapted strains of HIV-1. The extent of those functions in clinical strains is sometimes unknown. In this study, we amplified and sequenced HIV-1 Vpu from 10 Iranian patients infected with HIV-1. Phylogenetic analysis indicated that the Vpu alleles were closely related to the CRF35_AD from Iran and subtype A Vpu. We addressed some of the well-established functions of the HIV-1 Vpu, as well as some of its recently reported functions. Ability of the clinical strains of subtype A Vpu alleles for downregulation of CD4 was similar to that of the lab adapted NL4.3 Vpu. Majority of the subtype A Vpu alleles performed stronger than NL4.3 Vpu for downregulation of SNAT1. The Vpu alleles differentially induced downregulation of HLA-C, ranging from no effect to 88% downregulation of surface HLA-C. Downregulation of tetherin and enhancement of virus release was similar for the subtype A Vpu alleles and NL4.3. Subtype A Vpu alleles were more potent when compared with NL4.3 for inhibition of NF-κB activation. Our study shows that subtype A Vpu alleles exert the classical functions of HIV-1 Vpu.

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

    PubMed

    Suryawanshi, Gajendra W; Hoffmann, Alexander

    2015-12-07

    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 target

  12. A single amino acid substitution within the transmembrane domain of the human immunodeficiency virus type 1 Vpu protein renders simian-human immunodeficiency virus (SHIV{sub KU-1bMC33}) susceptible to rimantadine

    SciTech Connect

    Hout, David R.; Gomez, Lisa M.; Pacyniak, Erik; Miller, Jean-Marie; Hill, M. Sarah; Stephens, Edward B. . E-mail: estephen@kumc.edu

    2006-05-10

    Previous studies from our laboratory have shown that the transmembrane domain (TM) of the Vpu protein of human immunodeficiency virus type 1 (HIV-1) contributes to the pathogenesis of SHIV{sub KU-1bMC33} in macaques and that the TM domain of Vpu could be replaced with the M2 protein viroporin from influenza A virus. Recently, we showed that the replacement of the TM domain of Vpu with that of the M2 protein of influenza A virus resulted in a virus (SHIV{sub M2}) that was sensitive to rimantadine [Hout, D.R., Gomez, M.L., Pacyniak, E., Gomez, L.M., Inbody, S.H., Mulcahy, E.R., Culley, N., Pinson, D.M., Powers, M.F., Wong, S.W., Stephens, E.B., 2006. Substitution of the transmembrane domain of Vpu in simian human immunodeficiency virus (SHIV{sub KU-1bMC33}) with that of M2 of influenza A results in a virus that is sensitive to inhibitors of the M2 ion channel and is pathogenic for pig-tailed macaques. Virology 344, 541-558]. Based on previous studies of the M2 protein which have shown that the His-X-X-X-Trp motif within the M2 is essential to the function of the M2 proton channel, we have constructed a novel SHIV in which the alanine at position 19 of the TM domain was replaced with a histidine residue resulting in the motif His-Ile-Leu-Val-Trp. The SHIV{sub VpuA19H} replicated with similar kinetics as the parental SHIV{sub KU-1bMC33} and pulse-chase analysis revealed that the processing of viral proteins was similar to SHIV{sub KU-1bMC33}. This SHIV{sub VpuA19H} virus was found to be more sensitive to the M2 ion channel blocker rimantadine than SHIV{sub M2}. Electron microscopic examination of SHIV{sub VpuA19H}-infected cells treated with rimantadine revealed an accumulation of viral particles at the cell surface and within intracellular vesicles, which was similar to that previously observed to SHIV{sub M2}-infected cells treated with rimantadine. These data indicate that the Vpu protein of HIV-1 can be converted into a rimantadine-sensitive ion channel with the

  13. A model for the cytoplasmic domain of the influenza A virus M2 channel by analogy to the HIV-1 Vpu protein.

    PubMed

    Saldanha, José W; Czabotar, Peter E; Hay, Alan J; Taylor, William R

    2002-12-01

    A model for the cytoplasmic domain of the M2 proton channel of influenza A virus was formulated based primarily on the cytoplasmic domain of the Vpu protein of HIV-1 using sequence similarity and structure prediction techniques. The model consists of a pair of antiparallel helices followed by a strand parallel to the first helix. Structural analogies with other proteins contribute support for features of the model and suggest ways in which the M2 cytoplasmic domain can interact with other viral and cellular factors.

  14. Bacteria-Based Analysis of HIV-1 Vpu Channel Activity

    PubMed Central

    Taube, Robert; Alhadeff, Raphael; Assa, Dror; Krugliak, Miriam; Arkin, Isaiah T.

    2014-01-01

    HIV-1 Vpu is a small, single-span membrane protein with two attributed functions that increase the virus' pathogenicity: degradation of CD4 and inactivation of BST-2. Vpu has also been shown to posses ion channel activity, yet no correlation has been found between this attribute and Vpu's role in viral release. In order to gain further insight into the channel activity of Vpu we devised two bacteria-based assays that can examine this function in detail. In the first assay Vpu was over-expressed, such that it was deleterious to bacterial growth due to membrane permeabilization. In the second and more sensitive assay, the channel was expressed at low levels in K+ transport deficient bacteria. Consequently, Vpu expression enabled the bacteria to grow at otherwise non permissive low K+ concentrations. Hence, Vpu had the opposite impact on bacterial growth in the two assays: detrimental in the former and beneficial in the latter. Furthermore, we show that channel blockers also behave reciprocally in the two assays, promoting growth in the first assay and hindering it in the second assay. Taken together, we investigated Vpu's channel activity in a rapid and quantitative approach that is amenable to high-throughput screening, in search of novel blockers. PMID:25272035

  15. NMR studies for identifying phosphopeptide ligands of the HIV-1 protein Vpu binding to the F-box protein beta-TrCP.

    PubMed

    Evrard-Todeschi, Nathalie; Gharbi-Benarous, Josyane; Bertho, Gildas; Coadou, Gaël; Megy, Simon; Benarous, Richard; Girault, Jean-Pierre

    2006-01-01

    The human immunodeficiency virus type 1 (HIV-1) Vpu enhances viral particle release and, its interaction with the ubiquitin ligase SCF-beta-TrCP triggers the HIV-1 receptor CD4 degradation by the proteasome. The interaction between beta-TrCP protein and ligands containing the phosphorylated DpSGXXpS motif plays a key role for the development of severe disease states, such as HIV or cancer. This study examines the binding and conformation of phosphopeptides (P1, LIERAEDpSG and P2, EDpSGNEpSE) from HIV protein Vpu to beta-TrCP with the objective of defining the minimum length of peptide needed for effective binding. The screening step can be analyzed by NMR spectroscopy, in particular, saturation transfer NMR methods clearly identify the residues in the peptide that make direct contact with beta-TrCP protein when bound. An analysis of saturation transfer difference (STD) spectra provided clear evidence that the two peptides efficiently bound beta-TrCP receptor protein. To better characterize the ligand-protein interaction, the bound conformation of the phosphorylated peptides was determined using transferred NOESY methods, which gave rise to a well-defined structure. P1 and P2 can fold in a bend arrangement for the DpSG motif, showing the protons identified by STD-NMR as exposed in close proximity at the molecule surface. Ser phosphorylation allows electrostatic interaction and hydrogen bond with the amino acids of the beta-TrCP binding pocket. The upstream LIER hydrophobic region was also essential in binding to a hydrophobic pocket of the beta-TrCP WD domain. These findings are in good agreement with a recently published X-ray structure of a shorter beta-Catenin fragment with the beta-TrCP complex.

  16. 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)).

  17. Biophysical characterization of Vpu from HIV-1 suggests a channel-pore dualism.

    PubMed

    Mehnert, T; Routh, A; Judge, P J; Lam, Y H; Fischer, D; Watts, A; Fischer, W B

    2008-03-01

    Vpu from HIV-1 is an 81 amino acid type I integral membrane protein which consists of a cytoplasmic and a transmembrane (TM) domain. The TM domain is known to alter membrane permeability for ions and substrates when inserted into artificial membranes. Peptides corresponding to the TM domain of Vpu (Vpu(1-32)) and mutant peptides (Vpu(1-32)-W23L, Vpu(1-32)-R31V, Vpu(1-32)-S24L) have been synthesized and reconstituted into artificial lipid bilayers. All peptides show channel activity with a main conductance level of around 20 pS. Vpu(1-32)-W23L has a considerable flickering pattern in the recordings and longer open times than Vpu(1-32). Whilst recordings for Vpu(1-32)-R31V are almost indistinguishable from those of the WT peptide, recordings for Vpu(1-32)-S24L do not exhibit any noticeable channel activity. Recordings of WT peptide and Vpu(1-32)-W23L indicate Michaelis-Menten behavior when the salt concentration is increased. Both peptide channels follow the Eisenman series I, indicative for a weak ion channel with almost pore like characteristics.

  18. Species-Specific Activity of SIV Nef and HIV-1 Vpu in Overcoming Restriction by Tetherin/BST2

    PubMed Central

    Neidermyer, William; Rahmberg, Andrew; Mackey, John; Fofana, Ismael Ben; Johnson, Welkin E.; Westmoreland, Susan; Evans, David T.

    2009-01-01

    Tetherin, also known as BST2, CD317 or HM1.24, was recently identified as an interferon-inducible host–cell factor that interferes with the detachment of virus particles from infected cells. HIV-1 overcomes this restriction by expressing an accessory protein, Vpu, which counteracts tetherin. Since lentiviruses of the SIVsmm/mac/HIV-2 lineage do not have a vpu gene, this activity has likely been assumed by other viral gene products. We found that deletion of the SIVmac239 nef gene significantly impaired virus release in cells expressing rhesus macaque tetherin. Virus release could be restored by expressing Nef in trans. However, Nef was unable to facilitate virus release in the presence of human tetherin. Conversely, Vpu enhanced virus release in the presence of human tetherin, but not in the presence of rhesus tetherin. In accordance with the species-specificity of Nef in mediating virus release, SIV Nef downregulated cell-surface expression of rhesus tetherin, but did not downregulate human tetherin. The specificity of SIV Nef for rhesus tetherin mapped to four amino acids in the cytoplasmic domain of the molecule that are missing from human tetherin, whereas the specificity of Vpu for human tetherin mapped to amino acid differences in the transmembrane domain. Nef alleles of SIVsmm, HIV-2 and HIV-1 were also able to rescue virus release in the presence of both rhesus macaque and sooty mangabey tetherin, but were generally ineffective against human tetherin. Thus, the ability of Nef to antagonize tetherin from these Old World primates appears to be conserved among the primate lentiviruses. These results identify Nef as the viral gene product of SIV that opposes restriction by tetherin in rhesus macaques and sooty mangabeys, and reveal species-specificity in the activities of both Nef and Vpu in overcoming tetherin in their respective hosts. PMID:19436700

  19. Downmodulation of CCR7 by HIV-1 Vpu results in impaired migration and chemotactic signaling within CD4⁺ T cells.

    PubMed

    Ramirez, Peter W; Famiglietti, Marylinda; Sowrirajan, Bharatwaj; DePaula-Silva, Ana Beatriz; Rodesch, Christopher; Barker, Edward; Bosque, Alberto; Planelles, Vicente

    2014-06-26

    The chemokine receptor CCR7 plays a crucial role in the homing of central memory and naive T cells to peripheral lymphoid organs. Here, we show that the HIV-1 accessory protein Vpu downregulates CCR7 on the surface of CD4(+) T cells. Vpu and CCR7 were found to specifically interact and colocalize within the trans-Golgi network, where CCR7 is retained. Downmodulation of CCR7 did not involve degradation or endocytosis and was strictly dependent on Vpu expression. Stimulation of HIV-1-infected primary CD4(+) T cells with the CCR7 ligand CCL19 resulted in reduced mobilization of Ca(2+), reduced phosphorylation of Erk1/2, and impaired migration toward CCL19. Specific amino acid residues within the transmembrane domain of Vpu that were previously shown to be critical for BST-2 downmodulation (A14, A18, and W22) were also necessary for CCR7 downregulation. These results suggest that BST-2 and CCR7 may be downregulated via similar mechanisms.

  20. HIV-1 Vpu targets cell surface markers CD4 and BST-2 through distinct mechanisms

    PubMed Central

    Andrew, Amy; Strebel, Klaus

    2010-01-01

    Vpu is a small integral membrane protein encoded by HIV-1 and some SIV isolates. The protein is known to induce degradation of the viral receptor molecule CD4 and to enhance the release of newly formed virions from the cell surface. Vpu accomplishes these two functions through two distinct mechanisms. In the case of CD4, Vpu acts as a molecular adaptor to connect CD4 to an E3 ubiquitin ligase complex resulting in CD4 degradation by cellular proteasomes. This requires signals located in Vpu's cytoplasmic domain. Enhancement of virus release on the other hand involves the neutralization of a cellular host factor, BST-2 (also known as CD317, HM1.24, or tetherin) and requires Vpu's TM domain. The current review discusses recent advances on the role of Vpu in controlling degradation of CD4 and in regulating virus release. PMID:20858517

  1. Cell Surface Proteomic Map of HIV Infection Reveals Antagonism of Amino Acid Metabolism by Vpu and Nef

    PubMed Central

    Matheson, Nicholas J.; Sumner, Jonathan; Wals, Kim; Rapiteanu, Radu; Weekes, Michael P.; Vigan, Raphael; Weinelt, Julia; Schindler, Michael; Antrobus, Robin; Costa, Ana S.H.; Frezza, Christian; Clish, Clary B.; Neil, Stuart J.D.; Lehner, Paul J.

    2015-01-01

    Summary Critical cell surface immunoreceptors downregulated during HIV infection have previously been identified using non-systematic, candidate approaches. To gain a comprehensive, unbiased overview of how HIV infection remodels the T cell surface, we took a distinct, systems-level, quantitative proteomic approach. >100 plasma membrane proteins, many without characterized immune functions, were downregulated during HIV infection. Host factors targeted by the viral accessory proteins Vpu or Nef included the amino acid transporter SNAT1 and the serine carriers SERINC3/5. We focused on SNAT1, a β-TrCP-dependent Vpu substrate. SNAT1 antagonism was acquired by Vpu variants from the lineage of SIVcpz/HIV-1 viruses responsible for pandemic AIDS. We found marked SNAT1 induction in activated primary human CD4+ T cells, and used Consumption and Release (CoRe) metabolomics to identify alanine as an endogenous SNAT1 substrate required for T cell mitogenesis. Downregulation of SNAT1 therefore defines a unique paradigm of HIV interference with immunometabolism. PMID:26439863

  2. HIV-1 Vpu Promotes Release and Prevents Endocytosis of Nascent Retrovirus Particles from the Plasma Membrane

    PubMed Central

    Neil, Stuart J. D; Eastman, Scott W; Jouvenet, Nolwenn; Bieniasz, Paul D

    2006-01-01

    The human immunodeficiency virus (HIV) type-1 viral protein U (Vpu) protein enhances the release of diverse retroviruses from human, but not monkey, cells and is thought to do so by ablating a dominant restriction to particle release. Here, we determined how Vpu expression affects the subcellular distribution of HIV-1 and murine leukemia virus (MLV) Gag proteins in human cells where Vpu is, or is not, required for efficient particle release. In HeLa cells, where Vpu enhances HIV-1 and MLV release approximately 10-fold, concentrations of HIV-1 Gag and MLV Gag fused to cyan fluorescent protein (CFP) were initially detected at the plasma membrane, but then accumulated over time in early and late endosomes. Endosomal accumulation of Gag-CFP was prevented by Vpu expression and, importantly, inhibition of plasma membrane to early endosome transport by dominant negative mutants of Rab5a, dynamin, and EPS-15. Additionally, accumulation of both HIV and MLV Gag in endosomes required a functional late-budding domain. In human HOS cells, where HIV-1 and MLV release was efficient even in the absence of Vpu, Gag proteins were localized predominantly at the plasma membrane, irrespective of Vpu expression or manipulation of endocytic transport. While these data indicated that Vpu inhibits nascent virion endocytosis, Vpu did not affect transferrin endocytosis. Moreover, inhibition of endocytosis did not restore Vpu-defective HIV-1 release in HeLa cells, but instead resulted in accumulation of mature virions that could be released from the cell surface by protease treatment. Thus, these findings suggest that a specific activity that is present in HeLa cells, but not in HOS cells, and is counteracted by Vpu, traps assembled retrovirus particles at the cell surface. This entrapment leads to subsequent endocytosis by a Rab5a- and clathrin-dependent mechanism and intracellular sequestration of virions in endosomes. PMID:16699598

  3. 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.

  4. Multicopper manganese oxidase accessory proteins bind Cu and heme.

    PubMed

    Butterfield, Cristina N; Tao, Lizhi; Chacón, Kelly N; Spiro, Thomas G; Blackburn, Ninian J; Casey, William H; Britt, R David; Tebo, Bradley M

    2015-12-01

    Multicopper oxidases (MCOs) catalyze the oxidation of a diverse group of metal ions and organic substrates by successive single-electron transfers to O2 via four bound Cu ions. MnxG, which catalyzes MnO2 mineralization by oxidizing both Mn(II) and Mn(III), is unique among multicopper oxidases in that it carries out two energetically distinct electron transfers and is tightly bound to accessory proteins. There are two of these, MnxE and MnxF, both approximately 12kDa. Although their sequences are similar to those found in the genomes of several Mn-oxidizing Bacillus species, they are dissimilar to those of proteins with known function. Here, MnxE and MnxF are co-expressed independent of MnxG and are found to oligomerize into a higher order stoichiometry, likely a hexamer. They bind copper and heme, which have been characterized by electron paramagnetic resonance (EPR), X-ray absorption spectroscopy (XAS), and UV-visible (UV-vis) spectrophotometry. Cu is found in two distinct type 2 (T2) copper centers, one of which appears to be novel; heme is bound as a low-spin species, implying coordination by two axial ligands. MnxE and MnxF do not oxidize Mn in the absence of MnxG and are the first accessory proteins to be required by an MCO. This may indicate that Cu and heme play roles in electron transfer and/or Cu trafficking.

  5. Efficient Vpu-Mediated Tetherin Antagonism by an HIV-1 Group O Strain.

    PubMed

    Mack, Katharina; Starz, Kathrin; Sauter, Daniel; Langer, Simon; Bibollet-Ruche, Frederic; Learn, Gerald H; Stürzel, Christina M; Leoz, Marie; Plantier, Jean-Christophe; Geyer, Matthias; Hahn, Beatrice H; Kirchhoff, Frank

    2017-03-15

    Simian immunodeficiency viruses (SIVs) use their Nef proteins to counteract the restriction factor tetherin. However, a deletion in human tetherin prevents antagonism by the Nef proteins of SIVcpz and SIVgor, which represent the ape precursors of human immunodeficiency virus type 1 (HIV-1). To promote virus release from infected cells, pandemic HIV-1 group M strains evolved Vpu as a tetherin antagonist, while the Nef protein of less widespread HIV-1 group O strains acquired the ability to target a region adjacent to this deletion. In this study, we identified an unusual HIV-1 group O strain (RBF206) that evolved Vpu as an effective antagonist of human tetherin. While both RBF206 Vpu and Nef exert anti-tetherin activity in transient-transfection assays, mainly Vpu promotes RBF206 release in infected CD4(+) T cells. Although mutations distinct from the adaptive changes observed in group M Vpus (M-Vpus) were critical for the acquisition of its anti-tetherin activity, RBF206 O-Vpu potently suppresses NF-κB activation and reduces CD4 cell surface expression. Interestingly, RBF206 Vpu counteracts tetherin in a largely species-independent manner, degrading both the long and short isoforms of human tetherin. Downmodulation of CD4, but not counteraction of tetherin, by RBF206 Vpu was dependent on the cellular ubiquitin ligase machinery. Our data present the first example of an HIV-1 group O Vpu that efficiently antagonizes human tetherin and suggest that counteraction by O-Nefs may be suboptimal.IMPORTANCE Previous studies showed that HIV-1 groups M and O evolved two alternative strategies to counteract the human ortholog of the restriction factor tetherin. While HIV-1 group M switched from Nef to Vpu due to a deletion in the cytoplasmic domain of human tetherin, HIV-1 group O, which lacks Vpu-mediated anti-tetherin activity, acquired a Nef protein that is able to target a region adjacent to the deletion. Here we report an unusual exception, identifying a strain of HIV-1

  6. Genetic and phenotypic analyses of sequential vpu alleles from HIV-infected IFN-treated patients.

    PubMed

    Vanwalscappel, Bénédicte; Rato, Sylvie; Perez-Olmeda, Mayte; Díez Fuertes, Francisco; Casartelli, Nicoletta; Alcami, José; Mammano, Fabrizio

    2017-01-01

    Treatment of HIV-infected patients with IFN-α results in significant, but clinically insufficient, reductions of viremia. IFN induces the expression of several antiviral proteins including BST-2, which inhibits HIV by multiple mechanisms. The viral protein Vpu counteracts different effects of BST-2. We thus asked if Vpu proteins from IFN-treated patients displayed improved anti-BST-2 activities as compared to Vpu from baseline. Deep-sequencing analyses revealed that in five of seven patients treated by IFN-α for a concomitant HCV infection in the absence of antiretroviral drugs, the dominant Vpu sequences differed before and during treatment. In three patients, vpu alleles that emerged during treatment improved virus replication in the presence of IFN-α, and two of them conferred improved virus budding from cells expressing BST-2. Differences were observed for the ability to down-regulate CD4, while all Vpu variants potently down-modulated BST-2 from the cell surface. This report discloses relevant consequences of IFN-treatment on HIV properties.

  7. Envelope glycoprotein and CD4 independence of vpu-facilitated human immunodeficiency virus type 1 capsid export.

    PubMed Central

    Yao, X J; Göttlinger, H; Haseltine, W A; Cohen, E A

    1992-01-01

    The effect of vpu on the release of human immunodeficiency type 1 capsid proteins was examined in the presence or absence of virus-encoded envelope glycoproteins as well as in cells which constitutively express either the CD4 or CD8 protein. The results show that vpu-mediated facilitated export of capsid proteins from HeLa cells does not require expression of the envelope glycoprotein. The experiments also show that export of virus capsid proteins from HeLa cells facilitated by vpu is not affected by coexpression of either the CD4 or CD8 protein. The vpu protein acts in trans to facilitate export of virus capsid proteins from HeLa cells. Images PMID:1629967

  8. Identification of calcium-modulating cyclophilin ligand as a human host restriction to HIV-1 release overcome by Vpu

    PubMed Central

    Varthakavi, Vasundhara; Heimann-Nichols, Ellen; Smith, Rita M; Sun, Yuehui; Bram, Richard J; Ali, Showkat; Rose, Jeremy; Ding, Lingmei; Spearman, Paul

    2008-01-01

    The HIV-1 Vpu protein is required for efficient viral release from human cells. For HIV-2, the envelope (Env) protein replaces the role of Vpu. Both Vpu and HIV-2 Env enhance virus release by counteracting an innate host-cell block within human cells that is absent in African green monkey (AGM) cells. Here we identify calcium-modulating cyclophilin ligand (CAML) as a Vpu-interacting host factor that restricts HIV-1 release. Expression of human CAML (encoded by CAMLG) in AGM cells conferred a strong restriction of virus release that was reversed by Vpu and HIV-2 Env, suggesting that CAML is the mechanistic link between these two viral regulators. Depletion of CAML in human cells eliminated the need for Vpu in enhancing HIV-1 and murine leukemia virus release. These results point to CAML as a Vpu-sensitive host restriction factor that inhibits HIV release from human cells. The ability of CAML to inhibit virus release should illuminate new therapeutic strategies against HIV. PMID:18500349

  9. Mutation of a Single Residue Renders Human Tetherin Resistant to HIV-1 Vpu-Mediated Depletion

    PubMed Central

    Schaller, Torsten; Verschoor, Ernst; Pillay, Deenan; Towers, Greg J.

    2009-01-01

    The recently identified restriction factor tetherin/BST-2/CD317 is an interferon-inducible trans-membrane protein that restricts HIV-1 particle release in the absence of the HIV-1 countermeasure viral protein U (Vpu). It is known that Tantalus monkey CV1 cells can be rendered non-permissive to HIV-1 release upon stimulation with type 1 interferon, despite the presence of Vpu, suggesting species-specific sensitivity of tetherin proteins to viral countermeasures such as Vpu. Here we demonstrate that Tantalus monkey tetherin restricts HIV-1 by nearly two orders of magnitude, but in contrast to human tetherin the Tantalus protein is insensitive to HIV-1 Vpu. We have investigated tetherin's sensitivity to Vpu using positive selection analyses, seeking evidence for evolutionary conflict between tetherin and viral countermeasures. We provide evidence that tetherin has undergone positive selection during primate evolution. Mutation of a single amino acid (showing evidence of positive selection) in the trans-membrane cap of human tetherin to that in Tantalus monkey (T45I) substantially impacts on sensitivity to HIV-1 Vpu, but not on antiviral activity. Finally, we provide evidence that cellular steady state levels of tetherin are substantially reduced by Vpu, and that the T45I mutation abrogates this effect. This study provides evidence that tetherin is important in protecting mammals against viral infection, and that the HIV-1 Vpu–mediated countermeasure is specifically adapted to act against human tetherin. It also emphasizes the power of selection analyses to illuminate the molecular details of host–virus interactions. This work suggests that tetherin binding agents might protect it from viral encoded countermeasures and thus make powerful antivirals. PMID:19461879

  10. Vpu-Mediated Counteraction of Tetherin Is a Major Determinant of HIV-1 Interferon Resistance

    PubMed Central

    Kmiec, Dorota; Iyer, Shilpa S.; Stürzel, Christina M.; Sauter, Daniel; Hahn, Beatrice H.

    2016-01-01

    ABSTRACT Human immunodeficiency virus type 1 (HIV-1) groups M, N, O, and P are the result of independent zoonotic transmissions of simian immunodeficiency viruses (SIVs) infecting great apes in Africa. Among these, only Vpu proteins of pandemic HIV-1 group M strains evolved potent activity against the restriction factor tetherin, which inhibits virus release from infected cells. Thus, effective Vpu-mediated tetherin antagonism may have been a prerequisite for the global spread of HIV-1. To determine whether this particular function enhances primary HIV-1 replication and interferon resistance, we introduced mutations into the vpu genes of HIV-1 group M and N strains to specifically disrupt their ability to antagonize tetherin, but not other Vpu functions, such as degradation of CD4, down-modulation of CD1d and NTB-A, and suppression of NF-κB activity. Lack of particular human-specific adaptations reduced the ability of HIV-1 group M Vpu proteins to enhance virus production and release from primary CD4+ T cells at high levels of type I interferon (IFN) from about 5-fold to 2-fold. Interestingly, transmitted founder HIV-1 strains exhibited higher virion release capacity than chronic control HIV-1 strains irrespective of Vpu function, and group M viruses produced higher levels of cell-free virions than an N group HIV-1 strain. Thus, efficient virus release from infected cells seems to play an important role in the spread of HIV-1 in the human population and requires a fully functional Vpu protein that counteracts human tetherin. PMID:27531907

  11. Interaction of Proteus mirabilis Urease Apoenzyme and Accessory Proteins Identified with Yeast Two-Hybrid Technology

    PubMed Central

    Heimer, Susan R.; Mobley, Harry L. T.

    2001-01-01

    Proteus mirabilis, a gram-negative bacterium associated with complicated urinary tract infections, produces a metalloenzyme urease which hydrolyzes urea to ammonia and carbon dioxide. The apourease is comprised of three structural subunits, UreA, UreB, and UreC, assembled as a homotrimer of individual UreABC heterotrimers (UreABC)3. To become catalytically active, apourease acquires divalent nickel ions through a poorly understood process involving four accessory proteins, UreD, UreE, UreF, and UreG. While homologues of UreD, UreF, and UreG have been copurified with apourease, it remains unclear specifically how these polypeptides associate with the apourease or each other. To identify interactions among P. mirabilis accessory proteins, in vitro immunoprecipitation and in vivo yeast two-hybrid assays were employed. A complex containing accessory protein UreD and structural protein UreC was isolated by immunoprecipitation and characterized with immunoblots. This association occurs independently of coaccessory proteins UreE, UreF, and UreG and structural protein UreA. In a yeast two-hybrid screen, UreD was found to directly interact in vivo with coaccessory protein UreF. Unique homomultimeric interactions of UreD and UreF were also detected in vivo. To substantiate the study of urease proteins with a yeast two-hybrid assay, previously described UreE dimers and homomultimeric UreA interactions among apourease trimers were confirmed in vivo. Similarly, a known structural interaction involving UreA and UreC was also verified. This report suggests that in vivo, P. mirabilis UreD may be important for recruitment of UreF to the apourease and that crucial homomultimeric associations occur among these accessory proteins. PMID:11157956

  12. Carotenoid-binding proteins; accessories to carotenoid function.

    PubMed

    Pilbrow, Jodi; Garama, Daniel; Carne, Alan

    2012-01-01

    Understanding of the widespread biological importance of carotenoids is increasing. Accompanying this is the developing recognition that the interaction of carotenoids with other molecules, such as proteins, is also essential. Here the significance of carotenoid-protein interactions with respect to biological function is reviewed for three well characterised carotenoprotein complexes; crustacyanin, the orange carotenoid protein and glutathione-S-transferase P1. In addition a preliminary report is made on the recent partial purification of an echinenone-binding protein extracted from a New Zealand sea urchin, Evechinus chloroticus.

  13. Pandemic HIV-1 Vpu overcomes intrinsic herd immunity mediated by tetherin.

    PubMed

    Iwami, Shingo; Sato, Kei; Morita, Satoru; Inaba, Hisashi; Kobayashi, Tomoko; Takeuchi, Junko S; Kimura, Yuichi; Misawa, Naoko; Ren, Fengrong; Iwasa, Yoh; Aihara, Kazuyuki; Koyanagi, Yoshio

    2015-07-17

    Among the four groups of HIV-1 (M, N, O, and P), HIV-1M alone is pandemic and has rapidly expanded across the world. However, why HIV-1M has caused a devastating pandemic while the other groups remain contained is unclear. Interestingly, only HIV-1M Vpu, a viral protein, can robustly counteract human tetherin, which tethers budding virions. Therefore, we hypothesize that this property of HIV-1M Vpu facilitates human-to-human viral transmission. Adopting a multilayered experimental-mathematical approach, we demonstrate that HIV-1M Vpu confers a 2.38-fold increase in the prevalence of HIV-1 transmission. When Vpu activity is lost, protected human populations emerge (i.e., intrinsic herd immunity develops) through the anti-viral effect of tetherin. We also reveal that all Vpus of transmitted/founder HIV-1M viruses maintain anti-tetherin activity. These findings indicate that tetherin plays the role of a host restriction factor, providing 'intrinsic herd immunity', whereas Vpu has evolved in HIV-1M as a tetherin antagonist.

  14. 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.

  15. 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.

  16. Infectious Bronchitis Coronavirus Inhibits STAT1 Signaling and Requires Accessory Proteins for Resistance to Type I Interferon Activity

    PubMed Central

    Kint, Joeri; Dickhout, Annemiek; Kutter, Jasmin; Maier, Helena J.; Britton, Paul; Koumans, Joseph; Pijlman, Gorben P.; Fros, Jelke J.; Wiegertjes, Geert F.

    2015-01-01

    ABSTRACT The innate immune response is the first line of defense against viruses, and type I interferon (IFN) is a critical component of this response. Similar to other viruses, the gammacoronavirus infectious bronchitis virus (IBV) has evolved under evolutionary pressure to evade and counteract the IFN response to enable its survival. Previously, we reported that IBV induces a delayed activation of the IFN response. In the present work, we describe the resistance of IBV to IFN and the potential role of accessory proteins herein. We show that IBV is fairly resistant to the antiviral state induced by IFN and identify that viral accessory protein 3a is involved in resistance to IFN, as its absence renders IBV less resistant to IFN treatment. In addition to this, we found that independently of its accessory proteins, IBV inhibits IFN-mediated phosphorylation and translocation of STAT1. In summary, we show that IBV uses multiple strategies to counteract the IFN response. IMPORTANCE In the present study, we show that infectious bronchitis virus (IBV) is resistant to IFN treatment and identify a role for accessory protein 3a in the resistance against the type I IFN response. We also demonstrate that, in a time-dependent manner, IBV effectively interferes with IFN signaling and that its accessory proteins are dispensable for this activity. This study demonstrates that the gammacoronavirus IBV, similar to its mammalian counterparts, has evolved multiple strategies to efficiently counteract the IFN response of its avian host, and it identifies accessory protein 3a as multifaceted antagonist of the avian IFN system. PMID:26401035

  17. Characterization of monoclonal antibodies against feline coronavirus accessory protein 7b.

    PubMed

    Lemmermeyer, Tanja; Lamp, Benjamin; Schneider, Rainer; Ziebuhr, John; Tekes, Gergely; Thiel, Heinz-Jürgen

    2016-02-29

    Feline coronaviruses (FCoVs) encode five accessory proteins termed 3a, 3b, 3c, 7a and 7b of unknown function. These proteins are dispensable for viral replication in vitro but are supposed to play a role in virulence. In the current study, we produced and characterized 7b-specific monoclonal antibodies (mAbs). A recombinant form of the 7b protein was expressed as a fusion protein in Escherichia coli, purified by immobilized metal affinity chromatography and used as immunogen. Two hybridoma lines, 5B6 and 14D8, were isolated that expressed mAbs that recognized 7b proteins of both FCoV serotypes. Using an extensive set of N- and C-terminally truncated 7b proteins expressed in E. coli and a synthetic peptide, the binding sites of mAbs 5B6 and 14D8 were mapped to an 18-residue region that comprises the only potential N-glycosylation site of the FCoV 7b protein. The two mAbs were suitable to detect a 24-kDa protein, which represents the nonglycosylated form of 7b in FCoV-infected cells. We speculate that glycosylation of 7b is part of the viral evasion strategy to prevent an immune response against this antigenic site.

  18. A rev1-vpu polymorphism unique to HIV-1 subtype A and C strains impairs envelope glycoprotein expression from rev-vpu-env cassettes and reduces virion infectivity in pseudotyping assays

    SciTech Connect

    Kraus, Matthias H.; Parrish, Nicholas F.; Shaw, Katharina S.; Decker, Julie M.; Keele, Brandon F.; Salazar-Gonzalez, Jesus F.; Grayson, Truman; McPherson, David T.; Ping, Li-Hua; Anderson, Jeffrey A.; Swanstrom, Ronald; Williamson, Carolyn; Shaw, George M.; Hahn, Beatrice H.

    2010-02-20

    Functional studies of HIV-1 envelope glycoproteins (Envs) commonly include the generation of pseudoviruses, which are produced by co-transfection of rev-vpu-env cassettes with an env-deficient provirus. Here, we describe six Env constructs from transmitted/founder HIV-1 that were defective in the pseudotyping assay, although two produced infectious virions when expressed from their cognate proviruses. All of these constructs exhibited an unusual gene arrangement in which the first exon of rev (rev1) and vpu were in the same reading frame without an intervening stop codon. Disruption of the rev1-vpu fusion gene by frameshift mutation, stop codon, or abrogation of the rev initiation codon restored pseudovirion infectivity. Introduction of the fusion gene into wildtype Env cassettes severely compromised their function. The defect was not due to altered env and rev transcription or a dominant negative effect of the expressed fusion protein, but seemed to be caused by inefficient translation at the env initiation codon. Although the rev1-vpu polymorphism affects Env expression only in vitro, it can cause problems in studies requiring Env complementation, such as analyses of co-receptor usage and neutralization properties, since 3% of subtype A, 20% of subtype C and 5% of CRF01{sub A}/E viruses encode the fusion gene. A solution is to eliminate the rev initiation codon when amplifying rev-vpu-env cassettes since this increases Env expression irrespective of the presence of the polymorphism.

  19. The nonstructural protein 8 (nsp8) of the SARS coronavirus interacts with its ORF6 accessory protein

    SciTech Connect

    Kumar, Purnima; Gunalan, Vithiagaran; Liu Boping; Chow, Vincent T.K.; Druce, Julian; Birch, Chris; Catton, Mike; Fielding, Burtram C.; Tan, Yee-Joo; Lal, Sunil K.

    2007-09-30

    Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) caused a severe outbreak in several regions of the world in 2003. The SARS-CoV genome is predicted to contain 14 functional open reading frames (ORFs). The first ORF (1a and 1b) encodes a large polyprotein that is cleaved into nonstructural proteins (nsp). The other ORFs encode for four structural proteins (spike, membrane, nucleocapsid and envelope) as well as eight SARS-CoV-specific accessory proteins (3a, 3b, 6, 7a, 7b, 8a, 8b and 9b). In this report we have cloned the predicted nsp8 gene and the ORF6 gene of the SARS-CoV and studied their abilities to interact with each other. We expressed the two proteins as fusion proteins in the yeast two-hybrid system to demonstrate protein-protein interactions and tested the same using a yeast genetic cross. Further the strength of the interaction was measured by challenging growth of the positive interaction clones on increasing gradients of 2-amino trizole. The interaction was then verified by expressing both proteins separately in-vitro in a coupled-transcription translation system and by coimmunoprecipitation in mammalian cells. Finally, colocalization experiments were performed in SARS-CoV infected Vero E6 mammalian cells to confirm the nsp8-ORF6 interaction. To the best of our knowledge, this is the first report of the interaction between a SARS-CoV accessory protein and nsp8 and our findings suggest that ORF6 protein may play a role in virus replication.

  20. Structural mechanism for the regulation of HCN ion channels by the accessory protein TRIP8b

    PubMed Central

    DeBerg, Hannah A.; Bankston, John R.; Rosenbaum, Joel C.; Brzovic, Peter S.; Zagotta, William N.; Stoll, Stefan

    2015-01-01

    Summary Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels underlie the cationic Ih current present in many neurons. The direct binding of cAMP to HCN channels increases the rate and extent of channel opening and results in a depolarizing shift in the voltage dependence of activation. TRIP8b is an accessory protein that regulates the cell surface expression and dendritic localization of HCN channels and reduces the cyclic nucleotide dependence of these channels. Here we use electron paramagnetic resonance (EPR) to show that TRIP8b binds to the apo state of the cyclic nucleotide-binding domain (CNBD) of HCN2 channels without changing the overall domain structure. With EPR and nuclear magnetic resonance (NMR), we locate TRIP8b relative to the HCN channel and identify the binding interface on the CNBD. These data provide a structural framework for understanding how TRIP8b regulates the cyclic nucleotide dependence of HCN channels. PMID:25800552

  1. Crystal Structure of a Truncated Urease Accessory Protein UreF From Helicobacter pylori

    PubMed Central

    Lam, Robert; Romanov, Vladimir; Johns, Kathy; Battaile, Kevin P.; Wu-Brown, Jean; Guthrie, Jennifer L.; Hausinger, Robert P.; Pai, Emil F.; Chirgadze, Nickolay Y.

    2010-01-01

    Urease plays a central role in the pathogenesis of Helicobacter pylori in humans. Maturation of this nickel metalloenzyme in bacteria requires the participation of the accessory proteins UreD (termed UreH in H. pylori), UreF, and UreG which form sequential complexes with the urease apoprotein as well as UreE, a metallochaperone. Here, we describe the crystal structure of C-terminal truncated UreF from H. pylori (residues 1-233), the first UreF structure to be determined, at 1.55 Å resolution using SAD methods. UreF forms a dimer in vitro and adopts an all-helical fold congruent with secondary structure prediction. On the basis of evolutionary conservation analysis, the structure reveals a probable binding surface for interaction with other urease components as well as key conserved residues of potential functional relevance. PMID:20635345

  2. Proteome profiling reveals tissue-specific protein expression in male and female accessory glands of the silkworm, Bombyx mori.

    PubMed

    Dong, Zhaoming; Wang, Xiaohuan; Zhang, Yan; Zhang, Liping; Chen, Quanmei; Zhang, Xiaolu; Zhao, Ping; Xia, Qingyou

    2016-05-01

    Male accessory gland (MAG) and female accessory gland (FAG) of the reproductive system are, respectively, responsible for producing seminal proteins and adhesive proteins during copulation and ovulation. Seminal proteins are ejaculated to female along with sperms, whereas adhesive proteins are excreted along with eggs. Proteins from the male and female reproductive organs are usually indicative of rapid adaptive evolution. Understanding the reproductive isolation and species divergence requires identifying reproduction-related proteins from many different species. Here, we present our proteomic analyses of male and female accessory glands of the silkworm, Bombyx mori. Using LC/MS-MS, we identified 2133 MAG proteins and 1872 FAG proteins. In total, 652 proteins were significant more abundant in the MAG than in the FAG, including growth factors, odorant-binding proteins, enzymes, and proteins of unknown function. Growth factors and odorant-binding proteins are potential signaling molecules, whereas most of proteins of unknown function were found to be Lepidoptera-specific proteins with high evolutionary rates. Microarray experiments and semi-quantitative RT-PCR validated that MAG-specific proteins were expressed exclusively in male moths. Totally, 192 proteins were considered as FAG-specific proteins, including protease inhibitors, enzymes, and other proteins. Protease inhibitors were found to be the most abundant FAG-specific proteins, which may protect eggs from infection by inhibiting pathogen-derived proteases. These results provide comprehensive insights into copulation and oviposition. Moreover, the newly identified Lepidoptera-specific MAG proteins provide useful data for future research on the evolution of reproductive proteins in insects.

  3. 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

  4. ARC3 is a stromal Z-ring accessory protein essential for plastid division

    PubMed Central

    Maple, Jodi; Vojta, Lea; Soll, Jurgen; Møller, Simon G

    2007-01-01

    In plants, chloroplast division is an integral part of development, and these vital organelles arise by binary fission from pre-existing cytosolic plastids. Chloroplasts arose by endosymbiosis and although they have retained elements of the bacterial cell division machinery to execute plastid division, they have evolved to require two functionally distinct forms of the FtsZ protein and have lost elements of the Min machinery required for Z-ring placement. Here, we analyse the plastid division component accumulation and replication of chloroplasts 3 (ARC3) and show that ARC3 forms part of the stromal plastid division machinery. ARC3 interacts specifically with AtFtsZ1, acting as a Z-ring accessory protein and defining a unique function for this family of FtsZ proteins. ARC3 is involved in division site placement, suggesting that it might functionally replace MinC, representing an important advance in our understanding of the mechanism of chloroplast division and the evolution of the chloroplast division machinery. PMID:17304239

  5. An inducible packaging cell system for safe, efficient lentiviral vector production in the absence of HIV-1 accessory proteins.

    PubMed

    Pacchia, A L; Adelson, M E; Kaul, M; Ron, Y; Dougherty, J P

    2001-03-30

    Lentiviral vectors based on human immunodeficiency virus type 1 (HIV-1) possess the ability to deliver exogenous genes to both dividing and nondividing cells and to subsequently establish a stable provirus in these target cells, which can allow long-term expression of the transferred gene. Herein we describe a stable packaging cell line that is devoid of HIV-1 tat, vif, vpr, vpu, and nef. In order to avoid any risk of cytotoxicity associated with constitutive expression of HIV-1 protease or the VSV-G envelope protein, transcription of the packaging and envelope constructs was tightly controlled by employing the ecdysone-inducible system. Using this cell line, we have been able to consistently generate concentrated pseudotyped vector virus stocks with titers in the range of 10(8) IU/ml, which can efficiently transduce actively dividing and growth-arrested cells in vitro. This novel packaging cell line for lentiviral vectors facilitates the production of high-titer virus stocks in the absence of replication-competent virus and provides us with an important tool for use in future gene transfer studies.

  6. 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.

  7. Brain-specific interleukin-1 receptor accessory protein in sleep regulation.

    PubMed

    Taishi, Ping; Davis, Christopher J; Bayomy, Omar; Zielinski, Mark R; Liao, Fan; Clinton, James M; Smith, Dirk E; Krueger, James M

    2012-03-01

    Interleukin (IL)-1β is involved in several brain functions, including sleep regulation. It promotes non-rapid eye movement (NREM) sleep via the IL-1 type I receptor. IL-1β/IL-1 receptor complex signaling requires adaptor proteins, e.g., the IL-1 receptor brain-specific accessory protein (AcPb). We have cloned and characterized rat AcPb, which shares substantial homologies with mouse AcPb and, compared with AcP, is preferentially expressed in the brain. Furthermore, rat somatosensory cortex AcPb mRNA varied across the day with sleep propensity, increased after sleep deprivation, and was induced by somnogenic doses of IL-1β. Duration of NREM sleep was slightly shorter and duration of REM sleep was slightly longer in AcPb knockout than wild-type mice. In response to lipopolysaccharide, which is used to induce IL-1β, sleep responses were exaggerated in AcPb knockout mice, suggesting that, in normal mice, inflammation-mediated sleep responses are attenuated by AcPb. We conclude that AcPb has a role in sleep responses to inflammatory stimuli and, possibly, in physiological sleep regulation.

  8. Targeting TGFβ superfamily ligand accessory proteins as novel therapeutics for chronic lung disorders.

    PubMed

    Budd, David C; Holmes, Alan M

    2012-09-01

    Dysregulation of the transforming growth factor β (TGFβ) pathway has been implicated to underlie a number of disease indications including chronic lung disorders such as asthma, chronic obstructive pulmonary disease (COPD), interstitial pneumonias, and pulmonary arterial hypertension (PAH). Consequently, the pharmaceutical industry has devoted significant resources in the pursuit of TGFβ pathway inhibitors that target the cognate type I and II receptors and respective ligands. The progress of these approaches has been painfully slow, due in part to dose-limiting safety issues that result from the antagonism of a pathway that is responsible for regulating many fundamental biological processes including immune surveillance and cardiovascular responses. These disappointments have led many in the field to conclude that modulating the TGFβ pathway for chronic indications with a sufficient safety window using conventional approaches may be extremely difficult to achieve. Here we review the rationale and limitations of the use of TGFβ pathway inhibitors in chronic lung disorders and the possibility of targeting TGFβ superfamily ligand accessory proteins to allow rheostatic regulation of signaling to achieve efficacy while maintaining a sufficient therapeutic index.

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

    SciTech Connect

    Kim, Nam Soo; Kim, Yoon-Jin; Cho, Si Young; Lee, Tae Ryong; Kim, Sang Hoon

    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. Putative 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.

  10. A Critical Role for the GluA1 Accessory Protein, SAP97, in Cocaine Seeking

    PubMed Central

    White, Samantha L; Ortinski, Pavel I; Friedman, Shayna H; Zhang, Lei; Neve, Rachael L; Kalb, Robert G; Schmidt, Heath D; Pierce, R Christopher

    2016-01-01

    A growing body of evidence indicates that the transport of GluA1 subunit-containing calcium-permeable AMPA receptors (CP-AMPARs) to synapses in subregions of the nucleus accumbens promotes cocaine seeking. Consistent with these findings, the present results show that administration of the CP-AMPAR antagonist, Naspm, into the caudal lateral core or caudal medial shell of the nucleus accumbens attenuated cocaine priming-induced reinstatement of drug seeking. Moreover, viral-mediated overexpression of ‘pore dead' GluA1 subunits (via herpes simplex virus (HSV) GluA1-Q582E) in the lateral core or medial shell attenuated the reinstatement of cocaine seeking. The overexpression of wild-type GluA1 subunits (via HSV GluA1-WT) in the medial shell, but not the lateral core, enhanced the reinstatement of cocaine seeking. These results indicate that activation of GluA1-containing AMPARs in subregions of the nucleus accumbens reinstates cocaine seeking. SAP97 and 4.1N are proteins involved in GluA1 trafficking to and stabilization in synapses; SAP97-GluA1 interactions also influence dendritic growth. We next examined potential roles of SAP97 and 4.1N in cocaine seeking. Viral-mediated expression of a microRNA that reduces SAP97 protein expression (HSV miSAP97) in the medial accumbens shell attenuated cocaine seeking. In contrast, a virus that overexpressed a dominant-negative form of a 4.1N C-terminal domain (HSV 4.1N-CTD), which prevents endogenous 4.1N binding to GluA1 subunits, had no effect on cocaine seeking. These results indicate that the GluA1 subunit accessory protein SAP97 may represent a novel target for pharmacotherapeutic intervention in the treatment of cocaine craving. PMID:26149358

  11. PROTEIN KINASE Cα MEDIATES A NOVEL FORM OF PLASTICITY IN THE ACCESSORY OLFACTORY BULB

    PubMed Central

    DONG, C.; GODWIN, D. W.; BRENNAN, P. A.; HEGDE, A. N.

    2009-01-01

    Modification of synapses in the accessory olfactory bulb (AOB) is believed to underlie pheromonal memory that enables mate recognition in mice. The memory, which is acquired with single-trial learning forms only with coincident noradrenergic and glutamatergic inputs to the AOB. The mechanisms by which glutamate and norepinephrine (NE) alter the AOB synapses are not well understood. Here we present results that not only reconcile the earlier, seemingly contradictory, observations on the role of glutamate and NE in changing the AOB synapses, but also reveal novel mechanisms of plasticity. Our studies suggest that initially, glutamate acting at Group II metabotropic receptors and NE acting at α2-adrenergic receptors inhibit N-type and R-type Ca2+ channels in mitral cells via a G-Protein. The N-type and R-type Ca2+ channel inhibition is reversed by activation of α1-adrenergic receptors and protein kinase Cα (PKCα). Based on these results, we propose a hypothetical model for a new kind of synaptic plasticity in the AOB that accounts for the previous behavioral data on pheromonal memory. According to this model, initial inhibition of the Ca2+ channels suppresses the GABAergic inhibitory feedback to mitral cells, causing disinhibition and Ca2+ influx. NE also activates phospholipase C (PLC) through α1-adrenergic receptors generating inositol 1,4,5-trisphosphate and diacylglycerol (DAG). Calcium and DAG together activate protein kinase Cα (PKCα) which switches the disinhibition to increased inhibition of mitral cells. Thus, PKCα is likely to be a coincidence detector integrating glutamate and NE input in the AOB and bridging the short-term signaling to long-term structural changes resulting in enhanced inhibition of mitral cells that is thought to underlie memory formation. PMID:19580852

  12. Spo11-accessory proteins link double-strand break sites to the chromosome axis in early meiotic recombination.

    PubMed

    Panizza, Silvia; Mendoza, Marco A; Berlinger, Marc; Huang, Lingzhi; Nicolas, Alain; Shirahige, Katsuhiko; Klein, Franz

    2011-08-05

    Meiotic recombination between homologous chromosomes initiates via programmed DNA double-strand breaks (DSBs), generated by complexes comprising Spo11 transesterase plus accessory proteins. DSBs arise concomitantly with the development of axial chromosome structures, where the coalescence of axis sites produces linear arrays of chromatin loops. Recombining DNA sequences map to loops, but are ultimately tethered to the underlying axis. How and when such tethering occurs is currently unclear. Using ChIPchip in yeast, we show that Spo11-accessory proteins Rec114, Mer2, and Mei4 stably interact with chromosome axis sequences, upon phosphorylation of Mer2 by S phase Cdk. This axis tethering requires meiotic axis components (Red1/Hop1) and is modulated in a domain-specific fashion by cohesin. Loss of Rec114, Mer2, and Mei4 binding correlates with loss of DSBs. Our results strongly suggest that hotspot sequences become tethered to axis sites by the DSB machinery prior to DSB formation.

  13. DNMT3B isoforms without catalytic activity stimulate gene body methylation as accessory proteins in somatic cells.

    PubMed

    Duymich, Christopher E; Charlet, Jessica; Yang, Xiaojing; Jones, Peter A; Liang, Gangning

    2016-04-28

    Promoter DNA methylation is a key epigenetic mechanism for stable gene silencing, but is correlated with expression when located in gene bodies. Maintenance and de novo DNA methylation by catalytically active DNA methyltransferases (DNMT1 and DNMT3A/B) require accessory proteins such as UHRF1 and DNMT3L. DNMT3B isoforms are widely expressed, although some do not have active catalytic domains and their expression can be altered during cell development and tumourigenesis, questioning their biological roles. Here, we show that DNMT3B isoforms stimulate gene body methylation and re-methylation after methylation-inhibitor treatment. This occurs independently of the isoforms' catalytic activity, demonstrating a similar functional role to the accessory protein DNMT3L, which is only expressed in undifferentiated cells and recruits DNMT3A to initiate DNA methylation. This unexpected role for DNMT3B suggests that it might substitute for the absent accessory protein DNMT3L to recruit DNMT3A in somatic cells.

  14. Characterization of the Klebsiella aerogenes urease accessory protein UreD in fusion with the maltose binding protein.

    PubMed

    Carter, Eric L; Hausinger, Robert P

    2010-05-01

    Assembly of the Klebsiella aerogenes urease metallocenter requires four accessory proteins, UreD, UreE, UreF, and UreG, to effectively deliver and incorporate two Ni2+ ions into the nascent active site of the urease apoprotein (UreABC). Each accessory protein has been purified and characterized with the exception of UreD due to its insolubility when it is overproduced in recombinant cells. In this study, a translational fusion was made between the maltose binding protein (MBP) and UreD, with the resulting MBP-UreD found to be soluble in Escherichia coli cell extracts and able to complement a DeltaureD-urease cluster in this host microorganism. MBP-UreD was purified as a large multimer (> 670 kDa) that bound approximately 2.5 Ni2+ ions (K(d) of approximately 50 microM, where K(d) is the dissociation constant) per UreD protomer according to equilibrium dialysis measurements. Zn2+ directly competes with 10-fold higher affinity (approximately 4 Zn2+ ions per protomer; K(d) of 5 microM) for the Ni2+ binding sites. MBP pulldown experiments demonstrated that the UreD domain of MBP-UreD formed in vivo complexes with UreF, UreG, UreF plus UreG, or UreABC when these proteins were overproduced in the same E. coli cells. In addition, a UreABC-(MBP-UreD)-UreFG complex was observed in cells producing all urease components. Comparative in vitro binding experiments with purified proteins demonstrated an approximate 1:1 binding ratio between the UreD domain of MBP-UreD and the UreF domain of the UreEF fusion, only weak or transient interaction between MBP-UreD and UreG, and no binding with UreABC. These studies are the first to describe the properties of purified UreD, and they extend our understanding of its binding partners both in vitro and in the cell.

  15. Male Age Affects Female Mate Preference, Quantity of Accessory Gland Proteins, and Sperm Traits and Female Fitness in D. melanogaster.

    PubMed

    Rezaei, Abolhasan; Krishna, Mysore Siddaiah; Santhosh, Hassan T

    2015-01-01

    For species in which mating is resource-independent and offspring do not receive parental care, theoretical models of age-based female mate preference predict that females should prefer to mate with older males as they have demonstrated ability to survive. Thus, females should obtain a fitness benefit from mating with older males. However, male aging is often associated with reductions in quantity of sperm. The adaptive significance of age-based mate choice is therefore unclear. Various hypotheses have made conflicting predictions concerning this issue, because published studies have not investigated the effect of age on accessory gland proteins and sperm traits. D. melanogaster exhibits resource-independent mating, and offspring do not receive parental care, making this an appropriate model for studying age-based mate choice. In the present study, we found that D. melanogaster females of all ages preferred to mate with the younger of two competing males. Young males performed significantly greater courtship attempts and females showed least rejection for the same than middle-aged and old males. Young males had small accessory glands that contained very few main cells that were larger than average. Nevertheless, compared with middle-aged or old males, the young males transferred greater quantities of accessory gland proteins and sperm to mated females. As a result, females that mated with young male produced more eggs and progeny than those that mated with older males. Furthermore, mating with young male reduced female's lifespan. These studies indicate that quantity of accessory gland proteins and sperm traits decreased with male age and females obtain direct fitness benefit from mating with preferred young males.

  16. Middle East Respiratory Coronavirus Accessory Protein 4a Inhibits PKR-Mediated Antiviral Stress Responses

    PubMed Central

    Rabouw, Huib H.; Canton, Javier; Sola, Isabel; Enjuanes, Luis; Bredenbeek, Peter J.; Kikkert, Marjolein; de Groot, Raoul J.; van Kuppeveld, Frank J. M.

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infections that can be life-threatening. To establish an infection and spread, MERS-CoV, like most other viruses, must navigate through an intricate network of antiviral host responses. Besides the well-known type I interferon (IFN-α/β) response, the protein kinase R (PKR)-mediated stress response is being recognized as an important innate response pathway. Upon detecting viral dsRNA, PKR phosphorylates eIF2α, leading to the inhibition of cellular and viral translation and the formation of stress granules (SGs), which are increasingly recognized as platforms for antiviral signaling pathways. It is unknown whether cellular infection by MERS-CoV activates the stress response pathway or whether the virus has evolved strategies to suppress this infection-limiting pathway. Here, we show that cellular infection with MERS-CoV does not lead to the formation of SGs. By transiently expressing the MERS-CoV accessory proteins individually, we identified a role of protein 4a (p4a) in preventing activation of the stress response pathway. Expression of MERS-CoV p4a impeded dsRNA-mediated PKR activation, thereby rescuing translation inhibition and preventing SG formation. In contrast, p4a failed to suppress stress response pathway activation that is independent of PKR and dsRNA. MERS-CoV p4a is a dsRNA binding protein. Mutation of the dsRNA binding motif in p4a disrupted its PKR antagonistic activity. By inserting p4a in a picornavirus lacking its natural PKR antagonist, we showed that p4a exerts PKR antagonistic activity also under infection conditions. However, a recombinant MERS-CoV deficient in p4a expression still suppressed SG formation, indicating the expression of at least one other stress response antagonist. This virus also suppressed the dsRNA-independent stress response pathway. Thus, MERS-CoV interferes with antiviral stress responses using at least two different mechanisms, with p4a

  17. 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

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

    SciTech Connect

    Clark, A.G.; Prout, T.; Harshman, L.G.

    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 Drosophila 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. 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 to resist being displaced by subsequent sperm. This lack of correlation, and the association of Acp alleles with resisting subsequent sperm only, suggests that different mechanisms mediate the two components of sperm displacement. 36 refs., 4 figs., 7 tabs.

  19. 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.

  20. 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

  1. The accessory proteins REEP5 and REEP6 refine CXCR1-mediated cellular responses and lung cancer progression.

    PubMed

    Park, Cho Rong; You, Dong-Joo; Park, Sumi; Mander, Sunam; Jang, Da-Eun; Yeom, Su-Cheong; Oh, Seong-Hyun; Ahn, Curie; Lee, Sang Heon; Seong, Jae Young; Hwang, Jong-Ik

    2016-12-14

    Some G-protein-coupled receptors have been reported to require accessory proteins with specificity for proper functional expression. In this study, we found that CXCR1 interacted with REEP5 and REEP6, but CXCR2 did not. Overexpression of REEP5 and REEP6 enhanced IL-8-stimulated cellular responses through CXCR1, whereas depletion of the proteins led to the downregulation of the responses. Although REEPs enhanced the expression of a subset of GPCRs, in the absence of REEP5 and REEP6, CXCR1 was expressed in the plasma membrane, but receptor internalization and intracellular clustering of β-arrestin2 following IL-8 treatment were impaired, suggesting that REEP5 and REEP6 might be involved in the ligand-stimulated endocytosis of CXCR1 rather than membrane expression, which resulted in strong cellular responses. In A549 lung cancer cells, which endogenously express CXCR1, the depletion of REEP5 and REEP6 significantly reduced growth and invasion by downregulating IL-8-stimulated ERK phosphorylation, actin polymerization and the expression of genes related to metastasis. Furthermore, an in vivo xenograft model showed that proliferation and metastasis of A549 cells lacking REEP5 and REEP6 were markedly decreased compared to the control group. Thus, REEP5 and REEP6 could be novel regulators of G-protein-coupled receptor signaling whose functional mechanisms differ from other accessory proteins.

  2. The accessory proteins REEP5 and REEP6 refine CXCR1-mediated cellular responses and lung cancer progression

    PubMed Central

    Park, Cho Rong; You, Dong-Joo; Park, Sumi; Mander, Sunam; Jang, Da-Eun; Yeom, Su-Cheong; Oh, Seong-Hyun; Ahn, Curie; Lee, Sang Heon; Seong, Jae Young; Hwang, Jong-Ik

    2016-01-01

    Some G-protein-coupled receptors have been reported to require accessory proteins with specificity for proper functional expression. In this study, we found that CXCR1 interacted with REEP5 and REEP6, but CXCR2 did not. Overexpression of REEP5 and REEP6 enhanced IL-8-stimulated cellular responses through CXCR1, whereas depletion of the proteins led to the downregulation of the responses. Although REEPs enhanced the expression of a subset of GPCRs, in the absence of REEP5 and REEP6, CXCR1 was expressed in the plasma membrane, but receptor internalization and intracellular clustering of β-arrestin2 following IL-8 treatment were impaired, suggesting that REEP5 and REEP6 might be involved in the ligand-stimulated endocytosis of CXCR1 rather than membrane expression, which resulted in strong cellular responses. In A549 lung cancer cells, which endogenously express CXCR1, the depletion of REEP5 and REEP6 significantly reduced growth and invasion by downregulating IL-8-stimulated ERK phosphorylation, actin polymerization and the expression of genes related to metastasis. Furthermore, an in vivo xenograft model showed that proliferation and metastasis of A549 cells lacking REEP5 and REEP6 were markedly decreased compared to the control group. Thus, REEP5 and REEP6 could be novel regulators of G-protein-coupled receptor signaling whose functional mechanisms differ from other accessory proteins. PMID:27966653

  3. The role of accessory proteins in the replication of feline infectious peritonitis virus in peripheral blood monocytes.

    PubMed

    Dedeurwaerder, Annelike; Desmarets, Lowiese M; Olyslaegers, Dominique A J; Vermeulen, Ben L; Dewerchin, Hannah L; Nauwynck, Hans J

    2013-03-23

    The ability to productively infect monocytes/macrophages is the most important difference between the low virulent feline enteric coronavirus (FECV) and the lethal feline infectious peritonitis virus (FIPV). In vitro, the replication of FECV in peripheral blood monocytes always drops after 12h post inoculation, while FIPV sustains its replication in the monocytes from 45% of the cats. The accessory proteins of feline coronaviruses have been speculated to play a prominent role in virulence as deletions were found to be associated with attenuated viruses. Still, no functions have been ascribed to them. In order to investigate if the accessory proteins of FIPV are important for sustaining its replication in monocytes, replication kinetics were determined for FIPV 79-1146 and its deletion mutants, lacking either accessory protein open reading frame 3abc (FIPV-Δ3), 7ab (FIPV-Δ7) or both (FIPV-Δ3Δ7). Results showed that the deletion mutants FIPV-Δ7 and FIPV-Δ3Δ7 could not maintain their replication, which was in sharp contrast to wt-FIPV. FIPV-Δ3 could still sustain its replication, but the percentage of infected monocytes was always lower compared to wt-FIPV. In conclusion, this study showed that ORF7 is crucial for FIPV replication in monocytes/macrophages, giving an explanation for its importance in vivo, its role in the development of FIP and its conservation in field strains. The effect of an ORF3 deletion was less pronounced, indicating only a supportive role of ORF3 encoded proteins during the infection of the in vivo target cell by FIPVs.

  4. The Pediocin PA-1 Accessory Protein Ensures Correct Disulfide Bond Formation in the Antimicrobial Peptide Pediocin PA-1.

    PubMed

    Oppegård, Camilla; Fimland, Gunnar; Anonsen, Jan Haug; Nissen-Meyer, Jon

    2015-05-19

    Peptides, in contrast to proteins, are generally not large enough to form stable and well-defined three-dimensional structures. However, peptides are still able to form correct disulfide bonds. Using pediocin-like bacteriocins, we have examined how this may be achieved. Some pediocin-like bacteriocins, such as pediocin PA-1 and sakacin P[N24C+44C], have four cysteines. There are three possible ways by which the four cysteines may combine to form two disulfide bonds, and the three variants are expected to be produced in approximately equal amounts if their formation is random. Pediocin PA-1 and sakacin P[N24C+44C] with correct disulfide bonds were the main products when they were secreted by the pediocin PA-1 ABC transporter and accessory protein, but when they were secreted by the corresponding secretion machinery for sakacin A, a pediocin-like bacteriocin with one disulfide bond (two cysteines), peptides with all three possible disulfide bonds were produced in approximately equal amounts. All five cysteines in the pediocin PA-1 ABC transporter and the two cysteines (that form a CxxC motif) in the accessory protein were individually replaced with serines to examine their involvement in disulfide bond formation in pediocin PA-1. The Cys86Ser mutation in the accessory protein caused a 2-fold decrease in the amount of pediocin PA-1 with correct disulfide bonds, while the Cys83Ser mutation nearly abolished the production of pediocin PA-1 and resulted in the production of all three disufide bond variants in equal amounts. The Cys19Ser mutation in the ABC transporter completely abolished secretion of pediocin PA-1, suggesting that Cys19 is in the proteolytic active site and involved in cleaving the prebacteriocin. Replacing the other four cysteines in the ABC transporter with serines caused a slight reduction in the overall amount of secreted pediocin PA-1, but the relative amount with the correct disulfide bonds remained large. These results indicate that the pediocin

  5. Human Immunodeficiency Virus (HIV) Type 1 Vpu Induces the Expression of CD40 in Endothelial Cells and Regulates HIV-Induced Adhesion of B-Lymphoma Cells

    PubMed Central

    Henderson, Winnie W.; Ruhl, Rebecca; Lewis, Paul; Bentley, Matthew; Nelson, Jay A.; Moses, Ashlee V.

    2004-01-01

    AIDS-related B-cell non-Hodgkin's lymphoma (AIDS-NHL) is a significant cause of morbidity and mortality among individuals infected with human immunodeficiency virus type 1 (HIV-1). AIDS-NHL is clinically and histologically heterogeneous, but common features include an aggressive clinical course and frequent extranodal presentation. HIV-1 infection of nonimmune cells that interact with malignant B cells at extranodal sites may influence both the development and the clinical presentation of disease. Our previous studies have shown that coculture of B-lymphoma (BL) cells with HIV-1-infected endothelial cells (EC) leads to contact activation of EC and firm BL-cell adhesion. The key event promoting EC-BL-cell adhesion was HIV-1 upregulation of endothelial CD40, which allowed induction of vascular cell adhesion molecule 1 (VCAM-1) in a CD40-dependent manner. The present study was designed to identify the HIV-1 protein(s) that influence EC-BL-cell adhesion. When HIV-1 proteins were individually expressed in EC by using recombinant adenoviruses, cultured BL cells adhered exclusively to Vpu-transduced EC. As with HIV-infected EC, adhesive properties were linked to the capacity of Vpu to upregulate CD40, which in turn allowed efficient expression of VCAM-1. When EC were infected with an HIV-1 pseudotype lacking the Vpu gene, CD40 upregulation and BL-cell adhesive properties were lost, indicating an essential role for Vpu in EC-BL-cell interactions. Thus, these data reveal a novel function for HIV-1 Vpu and further suggest a role for Vpu in the development of AIDS-NHL at EC-rich extranodal sites. PMID:15078922

  6. Infectious Bronchitis Coronavirus Limits Interferon Production by Inducing a Host Shutoff That Requires Accessory Protein 5b

    PubMed Central

    Kint, Joeri; Langereis, Martijn A.; Maier, Helena J.; Britton, Paul; van Kuppeveld, Frank J.; Koumans, Joseph; Wiegertjes, Geert F.

    2016-01-01

    ABSTRACT During infection of their host cells, viruses often inhibit the production of host proteins, a process that is referred to as host shutoff. By doing this, viruses limit the production of antiviral proteins and increase production capacity for viral proteins. Coronaviruses from the genera Alphacoronavirus and Betacoronavirus, such as severe acute respiratory syndrome coronavirus (SARS-CoV), establish host shutoff via their nonstructural protein 1 (nsp1). The Gammacoronavirus and Deltacoronavirus genomes, however, do not encode nsp1, and it has been suggested that these viruses do not induce host shutoff. Here, we show that the Gammacoronavirus infectious bronchitis virus (IBV) does induce host shutoff, and we find that its accessory protein 5b is indispensable for this function. Importantly, we found that 5b-null viruses, unlike wild-type viruses, induce production of high concentrations of type I interferon protein in vitro, indicating that host shutoff by IBV plays an important role in antagonizing the host's innate immune response. Altogether, we demonstrate that 5b is a functional equivalent of nsp1, thereby answering the longstanding question of whether lack of nsp1 in gammacoronaviruses is compensated for by another viral protein. As such, our study is a significant step forward in the understanding of coronavirus biology and closes a gap in the understanding of some IBV virulence strategies. IMPORTANCE Many viruses inhibit protein synthesis by their host cell to enhance virus replication and to antagonize antiviral defense mechanisms. This process is referred to as host shutoff. We studied gene expression and protein synthesis in chicken cells infected with the important poultry pathogen infectious bronchitis virus (IBV). We show that IBV inhibits synthesis of host proteins, including that of type I interferon, a key component of the antiviral response. The IBV-induced host shutoff, however, does not require degradation of host RNA. Furthermore, we

  7. Electrophysiological Characteristics of the LQT2 Syndrome Mutation KCNH2-G572S and Regulation by Accessory Protein KCNE2

    PubMed Central

    Liu, Li; Tian, Jinwen; Lu, Caiyi; Chen, Xi; Fu, Yicheng; Xu, Bin; Zhu, Chao; Sun, Yanmei; Zhang, Yu; Zhao, Ying; Li, Yang

    2016-01-01

    Mutations in hERG cause long QT syndrome type 2 which is characterized by a prolonged QT interval on electrocardiogram and predisposition to life-threatening ventricular tachyarrhythmia, syncope, and sudden death. hERG-G572S induces trafficking defects of hERG channel protein from Golgi to the plasma membrane and results in a dominant negative suppression of hERG current density. As an accessory β subunit, KCNE2 promotes hERG migration from Golgi to cellular membrane. In this study, we investigated the rescue effect of KCNE2 in a G572S mutation of hERG. Transfection was performed into HEK293 cells. Patch clamp technique, western blotting analyses and confocal microscopic examination were used. Results showed that KCNE2 had a significantly enhanced effect on G572S mutation current. The increase of current was largest at KCNH2:KCNE2 of 1:3. Confocal images showed co-expressing G572S and KCNE2 could cause a substantial up-regulated membrane protein (155 kDa) expression. Expression of membrane protein accumulated markedly with increasing ratio of KCNH2:KCNE2. G572S defective mutant could be restored by both KCNE2 and lower temperature (27°C), which suggested that the lower temperature could be the favorable circumstances for the rescue function of KCNE2. In this study, we successfully set up “the action potential” on the HEK 293 cells by genetically engineered to express Kir2.1, Nav1.5, and Kv11.1, wherein on reaching over an excitation threshold by current injection. The results suggested that KCNE2 could shorten action potential duration which was prolonged by G572S. These findings described electrophysiological characteristics of the LQT2 syndrome mutation KCNH2-G572S and regulation by accessory protein KCNE2, and provided a clue about LQT2 and relative rescue mechanism. PMID:28082916

  8. Mycobacterium tuberculosis Proteasome Accessory Factor A (PafA) Can Transfer Prokaryotic Ubiquitin-Like Protein (Pup) between Substrates

    PubMed Central

    Zhang, Susan; Burns-Huang, Kristin E.; Janssen, Guido V.; Li, Huilin; Ovaa, Huib; Hedstrom, Lizbeth

    2017-01-01

    ABSTRACT The protein degradation machinery of Mycobacterium tuberculosis includes a proteasome and a ubiquitin-like protein (Pup). Proteasome accessory factor A (PafA) attaches Pup to proteins to target them for degradation by the proteasome. Free Pup is unstable and never observed in extracts of M. tuberculosis, an observation that led us to hypothesize that PafA may need alternative sources of Pup. Here, we show that PafA can move Pup from one proteasome substrate, inositol 1-phosphate synthetase (Ino1), to two different proteins, malonyl coenzyme A (CoA)-acyl carrier protein transacylase (FabD) and lonely guy (Log). This apparent “transpupylation” reaction required a previously unrecognized depupylase activity in PafA, and, surprisingly, this depupylase activity was much more efficient than the activity of the dedicated depupylase Dop (deamidase of Pup). Thus, PafA can potentially use both newly synthesized Pup and recycled Pup to doom proteins for degradation. PMID:28223451

  9. Structure of a D-protein gene and amino-acid sequences of the highly repetitive D-proteins secreted by the accessory glands of the mealworm beetle.

    PubMed

    Paesen, G C; Feng, X; Happ, G M

    1996-04-16

    The D-group proteins form the major component of the proteinaceous secretion of the tubular accessory glands of the yellow mealworm beetle, Tenebrio molitor. In a previous paper, we reported the sequence of two D-protein cDNAs and their inferred translation products. Both proteins contain three highly repetitive domains (A, A' and B). In this paper, we present the cDNA-inferred sequences of 8 more D-proteins, none of which contains an A' domain. We also present the structure of a D-protein gene. Southern analysis suggests that genes coding for an A' domain are relatively rare. Genes with a total of 7 or 8 (A + B domain) repeats seem most common.

  10. Guanylate binding protein 5: Impairing virion infectivity by targeting retroviral envelope glycoproteins.

    PubMed

    Hotter, Dominik; Sauter, Daniel; Kirchhoff, Frank

    2017-01-02

    Guanylate binding proteins (GBPs) are interferon-inducible cellular factors that belong to the superfamily of guanosine triphosphatases (GTPases) and play important roles in the cell-intrinsic defense against bacteria, protozoa and viruses. In a recent report in Cell Host & Microbe, we identify GBP5 as novel restriction factor of HIV-1 that reduces the infectivity of progeny virions by interfering with processing and incorporation of the viral envelope (Env) glycoprotein. The inhibitory activity of GBP5 requires C-terminal isoprenylation, mediating Golgi-association, but not its GTPase function. Notably, GBP5 expression levels vary considerably in human macrophages and inversely correlate with infectious virus yield. We demonstrate that GBP5 can be evaded by an unusual tradeoff mechanism: Naturally occurring mutations in the start codon of the viral accessory gene vpu attenuate GBP5 inhibition by increasing Env expression at the cost of Vpu function. Whether direct counteraction mechanisms or more subtle changes balancing Vpu and Env expression also affect HIV-1 inhibition by GBP5 remains to be clarified. Other open questions are whether GBP5 restricts HIV-1 in CD4(+) T cells and if other GBP family members also decrease infectivity of HIV and/or additional enveloped viruses.

  11. Guanylate binding protein 5: Impairing virion infectivity by targeting retroviral envelope glycoproteins

    PubMed Central

    Hotter, Dominik; Sauter, Daniel; Kirchhoff, Frank

    2017-01-01

    ABSTRACT Guanylate binding proteins (GBPs) are interferon-inducible cellular factors that belong to the superfamily of guanosine triphosphatases (GTPases) and play important roles in the cell-intrinsic defense against bacteria, protozoa and viruses. In a recent report in Cell Host & Microbe, we identify GBP5 as novel restriction factor of HIV-1 that reduces the infectivity of progeny virions by interfering with processing and incorporation of the viral envelope (Env) glycoprotein. The inhibitory activity of GBP5 requires C-terminal isoprenylation, mediating Golgi-association, but not its GTPase function. Notably, GBP5 expression levels vary considerably in human macrophages and inversely correlate with infectious virus yield. We demonstrate that GBP5 can be evaded by an unusual tradeoff mechanism: Naturally occurring mutations in the start codon of the viral accessory gene vpu attenuate GBP5 inhibition by increasing Env expression at the cost of Vpu function. Whether direct counteraction mechanisms or more subtle changes balancing Vpu and Env expression also affect HIV-1 inhibition by GBP5 remains to be clarified. Other open questions are whether GBP5 restricts HIV-1 in CD4+ T cells and if other GBP family members also decrease infectivity of HIV and/or additional enveloped viruses. PMID:27275775

  12. Elevated intracellular calcium triggers recruitment of the receptor cross-talk accessory protein calcyon to the plasma membrane.

    PubMed

    Ali, Mohammad Kutub; Bergson, Clare

    2003-12-19

    Calcyon is called a "cross-talk accessory protein" because the mechanism by which it enables the typically Gs-linked D1 dopamine receptor to stimulate intracellular calcium release depends on a priming step involving heterologous Gq-linked G-protein-coupled receptor activation. The details of how priming facilitates the D1R calcium response have yet to be precisely elucidated. The present work shows that calcyon is constitutively localized both in vesicular and plasma membrane compartments within HEK293 cells. In addition, surface biotinylation and luminescence assays revealed that priming stimulates a 2-fold increase in the levels of calcyon expressed on the cell surface and that subsequent D1R activation produces further accumulation of the protein in the plasma membrane. The effects of priming and D1R agonists were blocked by nocodazole implicating microtubules in the delivery of calcyon-containing vesicles to the cell surface. Accumulation of calcyon in the plasma membrane correlated well with increased intracellular calcium levels as thapsigargin mimicked, and 2-aminoethoxydiphenylborane abrogated, the effects of priming. KN-62, an inhibitor of calcium/calmodulin-dependent protein kinase II (CaMKII) also blocked the effects of priming and D1R agonists. Furthermore, expression of constitutively active forms of the kinase bypassed the requirement for priming indicating that CaMKII is a key effector in the Ca2+ and microtubule-dependent delivery of calcyon to the cell surface.

  13. Bivalent Motif-Ear Interactions Mediate the Association of the Accessory Protein Tepsin with the AP-4 Adaptor Complex.

    PubMed

    Mattera, Rafael; Guardia, Carlos M; Sidhu, Sachdev S; Bonifacino, Juan S

    2015-12-25

    The heterotetrameric (ϵ-β4-μ4-σ4) complex adaptor protein 4 (AP-4) is a component of a non-clathrin coat involved in protein sorting at the trans-Golgi network (TGN). Considerable interest in this complex has arisen from the recent discovery that mutations in each of its four subunits are the cause of a congenital intellectual disability and movement disorder in humans. Despite its physiological importance, the structure and function of this coat remain poorly understood. To investigate the assembly of the AP-4 coat, we dissected the determinants of interaction of AP-4 with its only known accessory protein, the ENTH/VHS-domain-containing protein tepsin. Using a variety of protein interaction assays, we found that tepsin comprises two phylogenetically conserved peptide motifs, [GS]LFXG[ML]X[LV] and S[AV]F[SA]FLN, within its C-terminal unstructured region, which interact with the C-terminal ear (or appendage) domains of the β4 and ϵ subunits of AP-4, respectively. Structure-based mutational analyses mapped the binding site for the [GS]LFXG[ML]X[LV] motif to a conserved, hydrophobic surface on the β4-ear platform fold. Both peptide-ear interactions are required for efficient association of tepsin with AP-4, and for recruitment of tepsin to the TGN. The bivalency of the interactions increases the avidity of tepsin for AP-4 and may enable cross-linking of multiple AP-4 heterotetramers, thus contributing to the assembly of the AP-4 coat. In addition to revealing critical aspects of this coat, our findings extend the paradigm of peptide-ear interactions, previously established for clathrin-AP-1/AP-2 coats, to a non-clathrin coat.

  14. Saturated palmitic acid induces myocardial inflammatory injuries through direct binding to TLR4 accessory protein MD2

    PubMed Central

    Wang, Yi; Qian, Yuanyuan; Fang, Qilu; Zhong, Peng; Li, Weixin; Wang, Lintao; Fu, Weitao; Zhang, Yali; Xu, Zheng; Li, Xiaokun; Liang, Guang

    2017-01-01

    Obesity increases the risk for a number of diseases including cardiovascular diseases and type 2 diabetes. Excess saturated fatty acids (SFAs) in obesity play a significant role in cardiovascular diseases by activating innate immunity responses. However, the mechanisms by which SFAs activate the innate immune system are not fully known. Here we report that palmitic acid (PA), the most abundant circulating SFA, induces myocardial inflammatory injury through the Toll-like receptor 4 (TLR4) accessory protein MD2 in mouse and cell culture experimental models. Md2 knockout mice are protected against PA- and high-fat diet-induced myocardial injury. Studies of cell surface binding, cell-free protein–protein interactions and molecular docking simulations indicate that PA directly binds to MD2, supporting a mechanism by which PA activates TLR4 and downstream inflammatory responses. We conclude that PA is a crucial contributor to obesity-associated myocardial injury, which is likely regulated via its direct binding to MD2. PMID:28045026

  15. Accessory proteins stabilize the acceptor complex for synaptobrevin, the 1:1 syntaxin/SNAP-25 complex

    PubMed Central

    Weninger, Keith; Bowen, Mark E.; Choi, Ucheor B.; Chu, Steven; Brunger, Axel T.

    2010-01-01

    Summary Formation of a binary complex between syntaxin and SNAP-25 (synaptosome-associated protein of 25 kDa) at the active zone is believed to precede assembly of the ternary SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex that is essential for neurotransmitter release. Despite its importance in models of synaptic neurotransmitter release, this binary complex has been difficult to characterize by bulk methods due to the prevalence of a 2:1 dead-end species. Here we used single molecule fluorescence resonance energy transfer (smFRET) to study the structure and dynamics of the 1:1 syntaxin/SNAP-25 binary complex. The binary complex is conformationally variable with FRET efficiency states often changing on the second timescale. One state corresponds to a parallel three-helix bundle configuration, while other states correspond to configurations with one of the SNAP-25 SNARE domains dissociated. All configurations of the binary complex are rapidly locked into the single three-helix bundle configuration by the addition of synaptobrevin. Remarkably, upon addition of complexin, Munc13, Munc18, or synaptotagmin, a similar effect is observed. Thus, the 1:1 binary complex serves as a dynamic acceptor for synaptobrevin binding, and interactions with accessory proteins stabilize this acceptor. In a high protein density cellular environment the syntaxin/SNAP-25 complex is therefore expected to be in the configuration where it can rapidly interact with synaptobrevin so its formation is unlikely a limiting step for SNARE-mediated neurotransmitter release. PMID:18275821

  16. Protein and Peptide Composition of Male Accessory Glands of Apis mellifera Drones Investigated by Mass Spectrometry.

    PubMed

    Gorshkov, Vladimir; Blenau, Wolfgang; Koeniger, Gudrun; Römpp, Andreas; Vilcinskas, Andreas; Spengler, Bernhard

    2015-01-01

    In honeybees, reproductive females usually mate early in their life with more than 10 males in free flight, often within 10 minutes, and then store male gametes for up to five years. Because of the extreme polyandry and mating in free flight special adaptations in males are most likely. We present here the results of an investigation of the protein content of four types of male reproductive glands from the Western honeybee (Apis mellifera) drone, namely seminal vesicles (secretion in ejaculate), as well as bulbus, cornua and mucus glands (secretions for the mating plug). Using high resolution and accuracy mass spectrometry and a combination of database searching and de novo sequencing techniques it was possible to identify 50 different proteins in total, inside all mentioned glands, except in the mucus gland. Most of the proteins are unique for a specific gland type, only one of them (H9KEY1/ATP synthase subunit O) was found in three glands, and 7 proteins were found in two types of glands. The identified proteins represent a wide variety of biological functions and can be assigned to several physiological classes, such as protection, energy generation, maintaining optimal conditions, associated mainly with vesicula seminalis; signaling, cuticle proteins, icarpin and apolipoproteins located mainly in the bulbus and cornua glands; and some other classes. Most of the discovered proteins were not found earlier during investigation of semen, seminal fluid and tissue of reproductive glands of the bee drone. Moreover, we provide here the origin of each protein. Thus, the presented data might shed light on the role of each reproductive gland.

  17. Interaction between the cytoplasmic domains of HIV-1 Vpu and CD4: role of Vpu residues involved in CD4 interaction and in vitro CD4 degradation.

    PubMed

    Margottin, F; Benichou, S; Durand, H; Richard, V; Liu, L X; Gomas, E; Benarous, R

    1996-09-15

    The Vpu and CD4 cytoplasmic domains were found, by using a two-hybrid assay in yeast, to interact in the absence of their membrane anchor domains. Studies on several deletion and point mutants revealed that the overall structure of the Vpu cytoplasmic domain is required for this interaction. The Vpu amino acid residues involved in the interaction with CD4 were identified. Deletion of the C-terminal residues of Vpu, required for CD4 degradation, as well as the double mutation on the casein kinase II phosphorylation sites S52N-S56N, also involved in CD4 degradation, resulted in the loss of interaction with CD4 and in the inability to induce CD4 degradation. These results suggest that the ability of Vpu to mediate the degradation of CD4 is linked to its capacity to physically interact with CD4. However, additional mutagenesis on the S52 site revealed that the interaction between the cytoplasmic domains of Vpu and CD4 is not sufficient for in vitro Vpu-mediated CD4 degradation.

  18. A defect in the retromer accessory protein, SNX27, manifests by infantile myoclonic epilepsy and neurodegeneration

    PubMed Central

    Al-Ashhab, Motee; Abu-Libdeh, Bassam; Gallon, Matthew; Sharma, Kanchan; Yaacov, Barak; Coulthard, Elizabeth; Caldwell, Maeve A.; Edvardson, Simon; Cullen, Peter J.; Elpeleg, Orly

    2016-01-01

    The composition of the neuronal cell surface dictates synaptic plasticity and thereby cognitive development. This remodeling of the synapses is governed by the endocytic network which internalize transmembrane proteins, then sort them back to the cell surface or carry them to the lysosome for degradation. The multi-protein retromer complex is central to this selection, capturing specific transmembrane proteins and remodeling the cell membrane to form isolated cargo-enriched transport carriers. We investigated a consanguineous family with four patients who presented in infancy with intractable myoclonic epilepsy and lack of psychomotor development. Using exome analysis, we identified a homozygous deleterious mutation in SNX27, which encodes sorting nexin 27, a retromer cargo adaptor. In western analysis of patient fibroblasts, the encoded mutant protein was expressed at an undetectable level when compared with a control sample. The patients’ presentation and clinical course recapitulate that reported for the SNX27 knock-out mouse. Since the cargo proteins for SNX27-mediated sorting include subunits of ionotropic glutamate receptors and endosome-to-cell surface synaptic insertion of AMPA receptors is severely perturbed in SNX27−/− neurons, it is proposed that at least part of the neurological aberrations observed in the patients is attributed to defective sorting of ionotropic glutamate receptors. SNX27 deficiency is now added to the growing list of neurodegenerative disorders associated with retromer dysfunction. PMID:25894286

  19. A Novel CNS-Restricted Isoform of the IL-1R Accessory Protein Modulates Neuronal Responses to IL-1

    PubMed Central

    Smith, Dirk E.; Lipsky, Brian P.; Russell, Chris; Ketchem, Randal R.; Kirchner, Jacqueline; Hensley, Kelly; Boissonneault, Vincent; Plante, Marie-Michèle; Rivest, Serge; Huang, Yangyang; Friedman, Wilma; Sims, John E.

    2014-01-01

    SUMMARY IL-1 has multiple functions in both the periphery and the central nervous system (CNS) and is regulated at many levels. We identified a novel isoform of the IL-1R Accessory Protein (termed AcPb) that is expressed exclusively in the CNS. AcPb interacted with IL-1 and the IL-1 receptor but was unable to mediate canonical IL-1 responses. AcPb expression, however, modulated neuronal gene expression in response to IL-1 treatment in vitro. Animals lacking AcPb demonstrated an intact peripheral IL-1 response and developed experimental autoimmune encephalomyelitis (EAE) similarly to wild type mice. AcPb-deficient mice were instead more vulnerable to local inflammatory challenge in the CNS and suffered enhanced neuronal degeneration as compared to AcP-deficient or wild type mice. These findings implicate AcPb as an additional component of the highly regulated IL-1 system and suggest it may play a role in modulating CNS responses to IL-1 and the interplay between inflammation and neuronal survival. PMID:19481478

  20. Male Accessory Gland Protein Reduces Egg Laying in a Simultaneous Hermaphrodite

    PubMed Central

    Koene, Joris M.; Sloot, Wiebe; Montagne-Wajer, Kora; Cummins, Scott F.; Degnan, Bernard M.; Smith, John S.; Nagle, Gregg T.; ter Maat, Andries

    2010-01-01

    Seminal fluid is an important part of the ejaculate of internally fertilizing animals. This fluid contains substances that nourish and activate sperm for successful fertilization. Additionally, it contains components that influence female physiology to further enhance fertilization success of the sperm donor, possibly beyond the recipient's optimum. Although evidence for such substances abounds, few studies have unraveled their identities, and focus has been exclusively on separate-sex species. We present the first detailed study into the seminal fluid composition of a hermaphrodite (Lymnaea stagnalis). Eight novel peptides and proteins were identified from the seminal-fluid-producing prostate gland and tested for effects on oviposition, hatching and consumption. The gene for the protein found to suppress egg mass production, Ovipostatin, was sequenced, thereby providing the first fully-characterized seminal fluid substance in a simultaneous hermaphrodite. Thus, seminal fluid peptides and proteins have evolved and can play a crucial role in sexual selection even when the sexes are combined. PMID:20404934

  1. Structure and intracellular targeting of the SARS-coronavirus Orf7a accessory protein.

    PubMed

    Nelson, Christopher A; Pekosz, Andrew; Lee, Chung A; Diamond, Michael S; Fremont, Daved H

    2005-01-01

    The open reading frame (ORF) 7a of the SARS-associated coronavirus (SARS-CoV) encodes a unique type I transmembrane protein of unknown function. We have determined the 1.8 A resolution crystal structure of the N-terminal ectodomain of orf7a, revealing a compact seven-stranded beta sandwich unexpectedly similar in fold and topology to members of the Ig superfamily. We also demonstrate that, in SARS-CoV- infected cells, the orf7a protein is expressed and retained intracellularly. Confocal microscopy studies using orf7a and orf7a/CD4 chimeras implicate the short cytoplasmic tail and transmembrane domain in trafficking of the protein within the endoplasmic reticulum and Golgi network. Taken together, our findings provide a structural and cellular framework in which to explore the role of orf7a in SARS-CoV pathogenesis.

  2. Manipulation of the infectious bronchitis coronavirus genome for vaccine development and analysis of the accessory proteins.

    PubMed

    Cavanagh, Dave; Casais, Rosa; Armesto, Maria; Hodgson, Teri; Izadkhasti, Sousan; Davies, Marc; Lin, Fengsheng; Tarpey, Ian; Britton, Paul

    2007-07-26

    Infectious bronchitis coronavirus (IBV) is the cause of the single most economically costly infectious disease of domestic fowl in the UK--and probably so in many countries that have a developed poultry industry. A major reason for its continued dominance is its existence as many serotypes, determined by the surface spike protein (S), cross-protection being poor. Although controlled to some degree by live and inactivated vaccines, a new generation of IB vaccines is called for. Reverse genetic or 'infectious clone' systems, which allow the manipulation of the IBV genome, are key to this development. New vaccines would ideally be: genetically stable (i.e. maintain a stable attenuated phenotype); administered in ovo; and be flexible with respect to the source of the spike protein gene. Rational attenuation of IBV requires the identification of genes that are simultaneously not essential for replication and whose absence would reduce pathogenicity. Being able to modify a 'core' vaccine strain to make it applicable to a prevailing serotype requires a procedure for doing so, and the demonstration that 'spike-swapping' is sufficient to induce good immunity. We have demonstrated that four small IBV proteins, encoded by genes 3 and 5, are not essential for replication; failure to produce these proteins had little detrimental affect on the titre of virus produced. Our current molecularly cloned IBV, strain Beaudette, is non-pathogenic, so we do not know what effect the absence of these proteins would have on pathogenicity. That said, plaque size and composition of various gene 3/5 recombinant IBVs in cell culture, and reduced output and ciliostasis in tracheal organ cultures, shows that they are less aggressive than the wild-type Beaudette. Consequently these genes remain targets for rational attenuation. We have recently obtained evidence that one or more of the 15 proteins encoded by gene 1 are also determinants of pathogenicity. Hence gene 1 is also a target for rational

  3. Functional Analysis of the Accessory Protein TapA in Bacillus subtilis Amyloid Fiber Assembly

    PubMed Central

    Romero, Diego; Vlamakis, Hera; Losick, Richard

    2014-01-01

    Bacillus subtilis biofilm formation relies on the assembly of a fibrous scaffold formed by the protein TasA. TasA polymerizes into highly stable fibers with biochemical and morphological features of functional amyloids. Previously, we showed that assembly of TasA fibers requires the auxiliary protein TapA. In this study, we investigated the roles of TapA sequences from the C-terminal and N-terminal ends and TapA cysteine residues in its ability to promote the assembly of TasA amyloid-like fibers. We found that the cysteine residues are not essential for the formation of TasA fibers, as their replacement by alanine residues resulted in only minor defects in biofilm formation. Mutating sequences in the C-terminal half had no effect on biofilm formation. However, we identified a sequence of 8 amino acids in the N terminus that is key for TasA fiber formation. Strains expressing TapA lacking these 8 residues were completely defective in biofilm formation. In addition, this TapA mutant protein exhibited a dominant negative effect on TasA fiber formation. Even in the presence of wild-type TapA, the mutant protein inhibited fiber assembly in vitro and delayed biofilm formation in vivo. We propose that this 8-residue sequence is crucial for the formation of amyloid-like fibers on the cell surface, perhaps by mediating the interaction between TapA or TapA and TasA molecules. PMID:24488317

  4. Olfactory receptor accessory proteins play crucial roles in receptor function and gene choice

    PubMed Central

    Sharma, Ruchira; Ishimaru, Yoshiro; Davison, Ian; Ikegami, Kentaro; Chien, Ming-Shan; You, Helena; Chi, Quiyi; Kubota, Momoka; Yohda, Masafumi; Ehlers, Michael; Matsunami, Hiroaki

    2017-01-01

    Each of the olfactory sensory neurons (OSNs) chooses to express a single G protein-coupled olfactory receptor (OR) from a pool of hundreds. Here, we show the receptor transporting protein (RTP) family members play a dual role in both normal OR trafficking and determining OR gene choice probabilities. Rtp1 and Rtp2 double knockout mice (RTP1,2DKO) show OR trafficking defects and decreased OSN activation. Surprisingly, we discovered a small subset of the ORs are expressed in larger numbers of OSNs despite the presence of fewer total OSNs in RTP1,2DKO. Unlike typical ORs, some overrepresented ORs show robust cell surface expression in heterologous cells without the co-expression of RTPs. We present a model in which developing OSNs exhibit unstable OR expression until they choose to express an OR that exits the ER or undergo cell death. Our study sheds light on the new link between OR protein trafficking and OR transcriptional regulation. DOI: http://dx.doi.org/10.7554/eLife.21895.001 PMID:28262096

  5. Pharmacogenomics of beta-adrenergic receptors and their accessory signaling proteins in heart failure.

    PubMed

    Dorn, Gerald W; Liggett, Stephen B

    2008-12-01

    beta-Adrenergic receptors (betaAR) are widely expressed on cardiovascular cells. Pharmacological stimulation or blockade of betaAR signaling is the therapeutic mainstay in cardiogenic shock, hypertension, ischemia, arrhythmias, and heart failure. Interindividual variability in the response to betaAR agonists and antagonists has prompted examination of variability in the genes encoding betaAR signaling pathway members. Prominent among the genes that have been examined so far in heart failure are the beta(1)AR, beta(2)AR, and G-protein-coupled receptor kinase 5 (GRK5). Each has nonsynonymous polymorphisms that alter amino acid sequence and protein function and regulation in cell-based systems, genetically altered mouse models, or human hearts. Here, we review these phenotypes and results from published clinical studies, with a focus on heart failure pharmacogenomics. Thus far, very few studies have utilized analogous protocols or drugs, and discrepancies in the clinical studies are apparent. A compelling approach is the use of multiple methods to understand the molecular, cellular, and organ phenotypes of a variant and couple these with clinical studies designed to specifically address the relevance of those phenotypes in humans. Undoubtedly, additional loci will be identified, and together, will provide for genetically driven, individualized treatments for heart failure.

  6. Drug Repurposing: Tolfenamic Acid Inactivates PrbP, a Transcriptional Accessory Protein in Liberibacter asiaticus

    PubMed Central

    Gardner, Christopher L.; Pagliai, Fernando A.; Pan, Lei; Bojilova, Lora; Torino, Maria I.; Lorca, Graciela L.; Gonzalez, Claudio F.

    2016-01-01

    CLIBASIA_01510, PrbP, is a predicted RNA polymerase binding protein in Liberibacter asiaticus. PrbP was found to regulate expression of a small subset of ribosomal genes through interactions with the β-subunit of the RNA polymerase and a short, specific sequence on the promoter region. Molecular screening assays were performed to identify small molecules that interact with PrbP in vitro. Chemical hits were analyzed for therapeutic efficacy against L. asiaticus via an infected leaf assay, where the transcriptional activity of L. asiaticus was found to decrease significantly after exposure to tolfenamic acid. Similarly, tolfenamic acid was found to inhibit L. asiaticus infection in highly symptomatic citrus seedlings. Our results indicate that PrbP is an important transcriptional regulator for survival of L. asiaticus in planta, and the chemicals identified by molecular screening assays could be used as a therapeutic treatment for huanglongbing disease. PMID:27803694

  7. Functional domains within the human immunodeficiency virus type 2 envelope protein required to enhance virus production.

    PubMed

    Abada, Paolo; Noble, Beth; Cannon, Paula M

    2005-03-01

    Primate lentiviruses code for a protein that stimulates virus production. In human immunodeficiency virus type 1 (HIV-1), the activity is provided by the accessory protein, Vpu, while in HIV-2 and simian immunodeficiency virus it is a property of the envelope (Env) glycoprotein. Using a group of diverse retroviruses and cell types, we have confirmed the functional equivalence of the two proteins. However, despite these similarities, the two proteins have markedly different functional domains. While the Vpu activity is associated primarily with its membrane-spanning region, we have determined that the HIV-2 Env activity requires both the cytoplasmic tail and ectodomain of the protein, with the membrane-spanning domain being less important. Within the Env cytoplasmic tail, we further defined the necessary sequence as a membrane-proximal tyrosine-based motif. Providing the two Env regions separately as distinct CD8 chimeric proteins did not increase virus release. This suggests that the two domains must be either contained within a single protein or closely associated within a multiprotein oligomer, such as the Env trimer, in order to function. Finally, we observed that wild-type levels of incorporation of the HIV-2 Env into budding viruses were not required for this activity.

  8. Functional Domains within the Human Immunodeficiency Virus Type 2 Envelope Protein Required To Enhance Virus Production

    PubMed Central

    Abada, Paolo; Noble, Beth; Cannon, Paula M.

    2005-01-01

    Primate lentiviruses code for a protein that stimulates virus production. In human immunodeficiency virus type 1 (HIV-1), the activity is provided by the accessory protein, Vpu, while in HIV-2 and simian immunodeficiency virus it is a property of the envelope (Env) glycoprotein. Using a group of diverse retroviruses and cell types, we have confirmed the functional equivalence of the two proteins. However, despite these similarities, the two proteins have markedly different functional domains. While the Vpu activity is associated primarily with its membrane-spanning region, we have determined that the HIV-2 Env activity requires both the cytoplasmic tail and ectodomain of the protein, with the membrane-spanning domain being less important. Within the Env cytoplasmic tail, we further defined the necessary sequence as a membrane-proximal tyrosine-based motif. Providing the two Env regions separately as distinct CD8 chimeric proteins did not increase virus release. This suggests that the two domains must be either contained within a single protein or closely associated within a multiprotein oligomer, such as the Env trimer, in order to function. Finally, we observed that wild-type levels of incorporation of the HIV-2 Env into budding viruses were not required for this activity. PMID:15731257

  9. Accessory proteins assist exonuclease-deficient bacteriophage T4 DNA polymerase in replicating past an abasic site

    PubMed Central

    Blanca, Giuseppina; Delagoutte, Emmanuelle; Tanguy le gac, Nicolas; Johnson, Neil P.; Baldacci, Giuseppe; Villani, Giuseppe

    2006-01-01

    Replicative DNA polymerases, such as T4 polymerase, possess both elongation and 3′–5′ exonuclease proofreading catalytic activities. They arrest at the base preceding DNA damage on the coding DNA strand and specialized DNA polymerases have evolved to replicate across the lesion by a process known as TLS (translesion DNA synthesis). TLS is considered to take place in two steps that often require different enzymes, insertion of a nucleotide opposite the damaged template base followed by extension from the inserted nucleotide. We and others have observed that inactivation of the 3′–5′ exonuclease function of T4 polymerase enables TLS across a single site-specific abasic [AP (apurinic/apyrimidinic)] lesion. In the present study we report a role for auxiliary replicative factors in this reaction. When replication is performed with a large excess of DNA template over DNA polymerase in the absence of auxiliary factors, the exo− polymerase (T4 DNA polymerase deficient in the 3′–5′ exonuclease activity) inserts one nucleotide opposite the AP site but does not extend past the lesion. Addition of the clamp processivity factor and the clamp loader complex restores primer extension across an AP lesion on a circular AP-containing DNA substrate by the exo− polymerase, but has no effect on the wild-type enzyme. Hence T4 DNA polymerase exhibits a variety of responses to DNA damage. It can behave as a replicative polymerase or (in the absence of proofreading activity) as a specialized DNA polymerase and carry out TLS. As a specialized polymerase it can function either as an inserter or (with the help of accessory proteins) as an extender. The capacity to separate these distinct functions in a single DNA polymerase provides insight into the biochemical requirements for translesion DNA synthesis. PMID:17064253

  10. Proteome analysis of male accessory gland secretions in oriental fruit flies reveals juvenile hormone-binding protein, suggesting impact on female reproduction.

    PubMed

    Wei, Dong; Li, Hui-Min; Tian, Chuan-Bei; Smagghe, Guy; Jia, Fu-Xian; Jiang, Hong-Bo; Dou, Wei; Wang, Jin-Jun

    2015-11-19

    In insects, the accessory gland proteins (Acps) secreted by male accessory glands (MAGs) account for the majority of seminal fluids proteins. Mixed with sperm, they are transferred to the female at mating and so impact reproduction. In this project, we identified 2,927 proteins in the MAG secretions of the oriental fruit fly Bactrocera dorsalis, an important agricultural pest worldwide, using LC-MS analysis, and all sequences containing open reading frames were analyzed using signalP. In total, 90 Acps were identified. About one third (26) of these 90 Acps had a specific functional description, while the other two thirds (64) had no functional description including dozens of new classes of proteins. Hence, several of these novel Acps were abundant in the MAG secretions, and we confirmed their MAG-specific expression by qPCR. Finally and interestingly, one of these novel proteins was functionally predicted as juvenile hormone-binding protein, suggesting the impact of Acps with reproductive events in the female. Our results will aid in the development of an experimental method to identify Acps in insects, and in turn this information with new Acps in B. dorsalis will pave the way of further exploration their function in reproduction and potential development as new insecticide targets.

  11. Proteome analysis of male accessory gland secretions in oriental fruit flies reveals juvenile hormone-binding protein, suggesting impact on female reproduction

    PubMed Central

    Wei, Dong; Li, Hui-Min; Tian, Chuan-Bei; Smagghe, Guy; Jia, Fu-Xian; Jiang, Hong-Bo; Dou, Wei; Wang, Jin-Jun

    2015-01-01

    In insects, the accessory gland proteins (Acps) secreted by male accessory glands (MAGs) account for the majority of seminal fluids proteins. Mixed with sperm, they are transferred to the female at mating and so impact reproduction. In this project, we identified 2,927 proteins in the MAG secretions of the oriental fruit fly Bactrocera dorsalis, an important agricultural pest worldwide, using LC-MS analysis, and all sequences containing open reading frames were analyzed using signalP. In total, 90 Acps were identified. About one third (26) of these 90 Acps had a specific functional description, while the other two thirds (64) had no functional description including dozens of new classes of proteins. Hence, several of these novel Acps were abundant in the MAG secretions, and we confirmed their MAG-specific expression by qPCR. Finally and interestingly, one of these novel proteins was functionally predicted as juvenile hormone-binding protein, suggesting the impact of Acps with reproductive events in the female. Our results will aid in the development of an experimental method to identify Acps in insects, and in turn this information with new Acps in B. dorsalis will pave the way of further exploration their function in reproduction and potential development as new insecticide targets. PMID:26582577

  12. IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exocytosis.

    PubMed

    Bahi, Nadia; Friocourt, Gaelle; Carrié, Alain; Graham, Margaret E; Weiss, Jamie L; Chafey, Philippe; Fauchereau, Fabien; Burgoyne, Robert D; Chelly, Jamel

    2003-06-15

    Previously, human genetics-based approaches allowed us to show that mutations in the IL-1 receptor accessory protein-like gene (IL1RAPL) are responsible for a non-specific form of X-linked mental retardation. This gene encodes a predicted protein of 696 amino acids that belongs to a novel class of the IL-1/Toll receptor family. In addition to the extracellular portion consisting of three Ig-like domains and the intracellular TIR domain characteristic of the IL-1/Toll receptor family, IL1RAPL contains a specific 150 amino acid carboxy terminus that has no significant homology with any protein of known function. In order to begin to elucidate the function of this IL-1/Toll receptor-like protein, we have assessed the effect of recombinant IL1RAPL on the binding affinity of type I IL-1R for its ligands IL-1alpha and beta and searched for proteins interacting with the specific carboxy terminus domain of IL1RAPL. Our results show that IL1RAPL is not a protein receptor for IL-1. In addition we present here the identification of Neuronal Calcium Sensor-1 (NCS-1) as an IL1RAPL interactor. Remarkably, although NCS-1 and its non-mammalian homologue, frequenin, are members of a highly conserved EF-hand Ca(2+) binding protein family, our data show that IL1RAPL interacts only with NCS-1 through its specific C-terminal domain. The functional relevance of IL1RAPL activity was further supported by the inhibitory effect on exocytosis in PC12 cells overexpressing IL1RAPL. Taken together, our data suggest that IL1RAPL may regulate calcium-dependent exocytosis and provide insight into the understanding of physiopathological mechanisms underlying cognitive impairment resulting from IL1RAPL dysfunction.

  13. IL1-receptor accessory protein-like 1 (IL1RAPL1), a protein involved in cognitive functions, regulates N-type Ca2+-channel and neurite elongation.

    PubMed

    Gambino, Frédéric; Pavlowsky, Alice; Béglé, Aurélie; Dupont, Jean-Luc; Bahi, Nadia; Courjaret, Raphael; Gardette, Robert; Hadjkacem, Hassen; Skala, Henriette; Poulain, Bernard; Chelly, Jamel; Vitale, Nicolas; Humeau, Yann

    2007-05-22

    Null mutations in the IL1-receptor accessory protein-like 1 gene (IL1RAPL1) are responsible for an inherited X-linked form of cognitive impairment. IL1RAPL1 protein physically interacts with neuronal calcium sensor-1 (NCS-1), but the functional impact of the IL1RAPL1/NCS-1 interaction remains unknown. Here, we demonstrate that stable expression of IL1RAPL1 in PC12 cells induces a specific silencing of N-type voltage-gated calcium channels (N-VGCC) activity that explains a secretion deficit observed in these IL1RAPL1 cells. Importantly, this modulation of VGCC activity is mediated by NCS-1. Indeed, a specific loss-of-function of N-VGCC was observed in PC12 cells overexpressing NCS-1, and a total recovery of N-VGCC activity was obtained by a down-regulation of NCS-1 in IL1RAPL1 cells. The functional relevance of the interaction between IL1RAPL1 and NCS-1 was also suggested by the reduction of neurite elongation observed in nerve growth factor (NGF)-treated IL1RAPL1 cells, a phenotype rescued by NCS-1 inactivation. Because both proteins are highly expressed in neurons, these results suggest that IL1RAPL1-related mental retardation could result from a disruption of N-VGCC and/or NCS-1-dependent synaptic and neuronal activities.

  14. The need to accessorize: molecular roles of HTLV-1 p30 and HTLV-2 p28 accessory proteins in the viral life cycle.

    PubMed

    Anupam, Rajaneesh; Doueiri, Rami; Green, Patrick L

    2013-09-17

    Extensive studies of human T-cell leukemia virus (HTLV)-1 and HTLV-2 over the last three decades have provided detailed knowledge on viral transformation, host-viral interactions and pathogenesis. HTLV-1 is the etiological agent of adult T cell leukemia and multiple neurodegenerative and inflammatory diseases while HTLV-2 disease association remains elusive, with few infected individuals displaying neurodegenerative diseases similar to HTLV-1. The HTLV group of oncoretroviruses has a genome that encodes structural and enzymatic proteins Gag, Pro, and Env, regulatory proteins Tax and Rex, and several accessory proteins from the pX region. Of these proteins, HTLV-1 p30 and HTLV-2 p28 are encoded by the open reading frame II of the pX region. Like most other accessory proteins, p30 and p28 are dispensable for in vitro viral replication and transformation but are required for efficient viral replication and persistence in vivo. Both p30 and p28 regulate viral gene expression at the post-transcriptional level whereas p30 can also function at the transcriptional level. Recently, several reports have implicated p30 and p28 in multiple cellular processes, which provide novel insight into HTLV spread and survival and ultimately pathogenesis. In this review we summarize and compare what is known about p30 and p28, highlighting their roles in viral replication and viral pathogenesis.

  15. Melanocortin receptor accessory protein 2 (MRAP2) interplays with the zebrafish melanocortin 1 receptor (MC1R) but has no effect on its pharmacological profile.

    PubMed

    Cortés, Raúl; Agulleiro, Maria Josep; Navarro, Sandra; Guillot, Raúl; Sánchez, Elisa; Cerdá-Reverter, José Miguel

    2014-05-15

    The melanocortin system is probably one of the most complex hormonal systems since it integrates agonist, encoded in the proopiomelanocortin precursor, endogenous antagonist, agouti signaling protein and agouti-related protein, five different G-protein coupled receptors and two accessory proteins. These accessory proteins interact with melanocortin receptors to allow traffic to the plasma membrane or to regulate the pharmacological profile. The MC1R fill the extension locus, which is primarily responsible for the regulation of pigmentation. In zebrafish, both MC1R and MRAP2 system are expressed in the skin. We demonstrate that zebrafish MC1R physically, or closely, interacts with the MRAP2 system, although this interaction did not result in modification of the studied pharmacological profile. However, progressive fasting induced skin darkening but also an upregulation of the MRAP2 expression in the skin, suggesting an unknown role for MRAP2a that could involve receptor desensitization processes. We also demonstrate that crowding stress induces skin darkening and a downregulation of MC1R expression in the skin.

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

    PubMed Central

    1988-01-01

    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

  17. 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.

  18. The ns12.9 Accessory Protein of Human Coronavirus OC43 Is a Viroporin Involved in Virion Morphogenesis and Pathogenesis

    PubMed Central

    Zhang, Ronghua; Wang, Kai; Ping, Xianqiang; Yu, Wenjing

    2015-01-01

    ABSTRACT An accessory gene between the S and E gene loci is contained in all coronaviruses (CoVs), and its function has been studied in some coronaviruses. This gene locus in human coronavirus OC43 (HCoV-OC43) encodes the ns12.9 accessory protein; however, its function during viral infection remains unknown. Here, we engineered a recombinant mutant virus lacking the ns12.9 protein (HCoV-OC43-Δns12.9) to characterize the contributions of ns12.9 in HCoV-OC43 replication. The ns12.9 accessory protein is a transmembrane protein and forms ion channels in both Xenopus oocytes and yeast through homo-oligomerization, suggesting that ns12.9 is a newly recognized viroporin. HCoV-OC43-Δns12.9 presented at least 10-fold reduction of viral titer in vitro and in vivo. Intriguingly, exogenous ns12.9 and heterologous viroporins with ion channel activity could compensate for the production of HCoV-OC43-Δns12.9, indicating that the ion channel activity of ns12.9 plays a significant role in the production of infectious virions. Systematic dissection of single-cycle replication revealed that ns12.9 protein had no measurable effect on virus entry, subgenomic mRNA (sgmRNA) synthesis, and protein expression. Further characterization revealed that HCoV-OC43-Δns12.9 was less efficient in virion morphogenesis than recombinant wild-type virus (HCoV-OC43-WT). Moreover, reduced viral replication, inflammatory response, and virulence in HCoV-OC43-Δns12.9-infected mice were observed compared to the levels for HCoV-OC43-WT-infected mice. Taken together, our results demonstrated that the ns12.9 accessory protein functions as a viroporin and is involved in virion morphogenesis and the pathogenesis of HCoV-OC43 infection. IMPORTANCE HCoV-OC43 was isolated in the 1960s and is a major agent of the common cold. The functions of HCoV-OC43 structural proteins have been well studied, but few studies have focused on its accessory proteins. In the present study, we demonstrated that the ns12.9 protein

  19. IL-1 receptor accessory protein-like 1 associated with mental retardation and autism mediates synapse formation by trans-synaptic interaction with protein tyrosine phosphatase δ.

    PubMed

    Yoshida, Tomoyuki; Yasumura, Misato; Uemura, Takeshi; Lee, Sung-Jin; Ra, Moonjin; Taguchi, Ryo; Iwakura, Yoichiro; Mishina, Masayoshi

    2011-09-21

    Mental retardation (MR) and autism are highly heterogeneous neurodevelopmental disorders. IL-1-receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic MR and is associated with autism. Thus, the elucidation of the functional role of IL1RAPL1 will contribute to our understanding of the pathogenesis of these mental disorders. Here, we showed that knockdown of endogenous IL1RAPL1 in cultured cortical neurons suppressed the accumulation of punctate staining signals for active zone protein Bassoon and decreased the number of dendritic protrusions. Consistently, the expression of IL1RAPL1 in cultured neurons stimulated the accumulation of Bassoon and spinogenesis. The extracellular domain (ECD) of IL1RAPL1 was required and sufficient for the presynaptic differentiation-inducing activity, while both the ECD and cytoplasmic domain were essential for the spinogenic activity. Notably, the synaptogenic activity of IL1RAPL1 was specific for excitatory synapses. Furthermore, we identified presynaptic protein tyrosine phosphatase (PTP) δ as a major IL1RAPL1-ECD interacting protein by affinity chromatography. IL1RAPL1 interacted selectively with certain forms of PTPδ splice variants carrying mini-exon peptides in Ig-like domains. The synaptogenic activity of IL1RAPL1 was abolished in primary neurons from PTPδ knock-out mice. IL1RAPL1 showed robust synaptogenic activity in vivo when transfected into the cortical neurons of wild-type mice but not in PTPδ knock-out mice. These results suggest that IL1RAPL1 mediates synapse formation through trans-synaptic interaction with PTPδ. Our findings raise an intriguing possibility that the impairment of synapse formation may underlie certain forms of MR and autism as a common pathogenic pathway shared by these mental disorders.

  20. Vpu Exploits the Cross-Talk between BST2 and the ILT7 Receptor to Suppress Anti-HIV-1 Responses by Plasmacytoid Dendritic Cells

    PubMed Central

    Bego, Mariana G.; Côté, Édouard; Aschman, Nick; Mercier, Johanne; Weissenhorn, Winfried; Cohen, Éric A.

    2015-01-01

    Plasmacytoid dendritic cells (pDCs) constitute a major source of type-I interferon (IFN-I) production during acute HIV infection. Their activation results primarily from TLR7-mediated sensing of HIV-infected cells. However, the interactions between HIV-infected T cells and pDCs that modulate this sensing process remain poorly understood. BST2/Tetherin is a restriction factor that inhibits HIV release by cross-linking virions onto infected cell surface. BST2 was also shown to engage the ILT7 pDC-specific inhibitory receptor and repress TLR7/9-mediated IFN-I production by activated pDCs. Here, we show that Vpu, the HIV-1 antagonist of BST2, suppresses TLR7-mediated IFN-I production by pDC through a mechanism that relies on the interaction of BST2 on HIV-producing cells with ILT7. Even though Vpu downregulates surface BST2 as a mean to counteract the restriction on HIV-1 release, we also find that the viral protein re-locates remaining BST2 molecules outside viral assembly sites where they are free to bind and activate ILT7 upon cell-to-cell contact. This study shows that through a targeted regulation of surface BST2, Vpu promotes HIV-1 release and limits pDC antiviral responses upon sensing of infected cells. This mechanism of innate immune evasion is likely to be important for an efficient early viral dissemination during acute infection. PMID:26172439

  1. The interleukin 1 (IL-1) receptor accessory protein Toll/IL-1 receptor domain: analysis of putative interaction sites in vitro mutagenesis and molecular modeling.

    PubMed

    Radons, Jurgen; Dove, Stefan; Neumann, Detlef; Altmann, Reinhold; Botzki, Alexander; Martin, Michael U; Falk, Werner

    2003-12-05

    The Toll/interleukin 1 (IL-1) receptor family plays an important role in both innate and adaptive immunity. These receptors are characterized by a C-terminal homology motif called the Toll/IL-1 receptor (TIR) domain. A principal function of the TIR domain is mediating homotypic protein-protein interactions in the signal transduction pathway. To suggest interaction sites of TIR domains in the IL-1 receptor complex, we modeled the putative three-dimensional structure of the TIR domain within the co-receptor chain, IL-1 receptor accessory protein. The model was based on homology with the crystal structures of human TLR1 and TLR2. The final structure of the IL-1 receptor accessory protein TIR domain suggests the conserved regions box 1 and 2, including Pro-446, as well as box 3 within the C-terminal alpha-helix as possible protein-protein interaction sites due to their exposure and their electrostatic potential. Pro-446, corresponding to the Pro/His mutation in dominant negative TLR4, is located in the third loop at the outmost edge of the TIR domain and does not play any structural role. Inhibition of IL-1 responsiveness seen after substitution of Pro-446 by charged amino acids is due to the loss of an interaction site for other TIR domains. Amino acids 527-534 as part of the loop close to the conserved box 3 are critical for recruitment of myeloid differentiation factor 88 and to a lesser extent for IL-1 responsiveness. Modeling suggests that native folding of the TIR domain may be approached by the responsive deletion mutants delta528-534 and delta527-533, whereas the C-terminal beta-strand and/or alpha-helix is displaced in the nonresponsive mutant delta527-534.

  2. Validating Vegetable Production Unit (VPU) Plants, Protocols, Procedures and Requirements (P3R) using Currently Existing Flight Resources

    NASA Technical Reports Server (NTRS)

    Bingham, Gail; Bates, Scott; Bugbee, Bruce; Garland, Jay; Podolski, Igor; Levinskikh, Rita; Sychev, Vladimir; Gushin, Vadim

    2009-01-01

    Validating Vegetable Production Unit (VPU) Plants, Protocols, Procedures and Requirements (P3R) Using Currently Existing Flight Resources (Lada-VPU-P3R) is a study to advance the technology required for plant growth in microgravity and to research related food safety issues. Lada-VPU-P3R also investigates the non-nutritional value to the flight crew of developing plants on-orbit. The Lada-VPU-P3R uses the Lada hardware on the ISS and falls under a cooperative agreement between National Aeronautics and Space Administration (NASA) and the Russian Federal Space Association (FSA). Research Summary: Validating Vegetable Production Unit (VPU) Plants, Protocols, Procedures and Requirements (P3R) Using Currently Existing Flight Resources (Lada-VPU-P3R) will optimize hardware and

  3. The Vpr protein from HIV-1: distinct roles along the viral life cycle

    PubMed Central

    Le Rouzic, Erwann; Benichou, Serge

    2005-01-01

    The genomes of human and simian immunodeficiency viruses (HIV and SIV) encode the gag, pol and env genes and contain at least six supplementary open reading frames termed tat, rev, nef, vif, vpr, vpx and vpu. While the tat and rev genes encode regulatory proteins absolutely required for virus replication, nef, vif, vpr, vpx and vpu encode for small proteins referred to "auxiliary" (or "accessory"), since their expression is usually dispensable for virus growth in many in vitro systems. However, these auxiliary proteins are essential for viral replication and pathogenesis in vivo. The two vpr- and vpx-related genes are found only in members of the HIV-2/SIVsm/SIVmac group, whereas primate lentiviruses from other lineages (HIV-1, SIVcpz, SIVagm, SIVmnd and SIVsyk) contain a single vpr gene. In this review, we will mainly focus on vpr from HIV-1 and discuss the most recent developments in our understanding of Vpr functions and its role during the virus replication cycle. PMID:15725353

  4. 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

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

    PubMed

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

    2014-11-01

    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 A. 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 48 h 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.

  6. 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.

  7. HIV-1 Vpu's lipid raft association is dispensable for counteraction of the particle release restriction imposed by CD317/Tetherin

    SciTech Connect

    Fritz, Joeelle V. Tibroni, Nadine Keppler, Oliver T. Fackler, Oliver T.

    2012-03-01

    HIV-1 Vpu antagonizes the block to particle release mediated by CD317 (BST-2/HM1.24/Tetherin) via incompletely understood mechanisms. Vpu and CD317 partially reside in cholesterol-rich lipid rafts where HIV-1 budding preferentially occurs. Here we find that lipid raft association of ectopically expressed or endogenous CD317 was unaltered upon co-expression with Vpu or following HIV-1 infection. Similarly, Vpu's lipid raft association remained unchanged upon expression of CD317. We identify amino acids V25 and Y29 of Vpu as crucial for microdomain partitioning and single substitution of these amino acids resulted in Vpu variants with markedly reduced or undetectable lipid raft association. These mutations did not affect Vpu's subcellular distribution and binding capacity to CD317, nor its ability to downmodulate cell surface CD317 and promote HIV-1 release from CD317-positive cells. We conclude that (i) lipid raft incorporation is dispensable for Vpu-mediated CD317 antagonism and (ii) Vpu does not antagonize CD317 by extraction from lipid rafts.

  8. Substitution of the transmembrane domain of Vpu in simian-human immunodeficiency virus (SHIV{sub KU1bMC33}) with that of M2 of influenza A results in a virus that is sensitive to inhibitors of the M2 ion channel and is pathogenic for pig-tailed macaques

    SciTech Connect

    Hout, David R.; Gomez, Melissa L.; Pacyniak, Erik; Gomez, Lisa M.; Fegley, Barbara; Mulcahy, Ellyn R.; Hill, M. Sarah; Culley, Nathan; Pinson, David M.; Nothnick, Warren; Powers, Michael F.; Wong, Scott W.; Stephens, Edward B. . E-mail: estephen@kumc.edu

    2006-01-20

    The Vpu protein of human immunodeficiency virus type 1 has been shown to shunt the CD4 receptor molecule to the proteasome for degradation and to enhance virus release from infected cells. The exact mechanism by which the Vpu protein enhances virus release is currently unknown but some investigators have shown that this function is associated with the transmembrane domain and potential ion channel properties. In this study, we determined if the transmembrane domain of Vpu could be functionally substituted with that of the prototypical viroporin, the M2 protein of influenza A virus. We constructed chimeric vpu gene in which the transmembrane domain of Vpu was replaced with that of the M2 protein of influenza. This chimeric vpu gene was substituted for the vpu gene in the genome of a pathogenic simian human immunodeficiency virus, SHIV{sub KU-1bMC33}. The resulting virus, SHIV{sub M2}, synthesized a Vpu protein that had a slightly different M{sub r} compared to the parental SHIV{sub KU-1bMC33}, reflecting the different sizes of the two Vpu proteins. The SHIV{sub M2} was shown to replicate with slightly reduced kinetics when compared to the parental SHIV{sub KU-1bMC33} but electron microscopy revealed that the site of maturation was similar to the parental virus SHIV{sub KU1bMC33}. We show that the replication and spread of SHIV{sub M2} could be blocked with the antiviral drug rimantadine, which is known to target the M2 ion channel. Our results indicate a dose dependent inhibition of SHIV{sub M2} with 100 {mu}M rimantadine resulting in a >95% decrease in p27 released into the culture medium. Rimantadine did not affect the replication of the parental SHIV{sub KU-1bMC33}. Examination of SHIV{sub M2}-infected cells treated with 50 {mu}M rimantadine revealed numerous viral particles associated with the cell plasma membrane and within intracytoplasmic vesicles, which is similar to HIV-1 mutants lacking a functional vpu. To determine if SHIV{sub M2} was as pathogenic as

  9. Unusual Fusion Proteins of HIV-1

    PubMed Central

    Langer, Simon; Sauter, Daniel

    2017-01-01

    Despite its small genome size, the Human Immunodeficiency Virus 1 (HIV-1) is one of the most successful pathogens and has infected more than 70 million people worldwide within the last decades. In total, HIV-1 expresses 16 canonical proteins from only nine genes within its 10 kb genome. Expression of the structural genes gag, pol, and env, the regulatory genes rev and tat and the accessory genes vpu, nef, vpr, and vif enables assembly of the viral particle, regulates viral gene transcription, and equips the virus to evade or counteract host immune responses. In addition to the canonically expressed proteins, a growing number of publications describe the existence of non-canonical fusion proteins in HIV-1 infected cells. Most of them are encoded by the tat-env-rev locus. While the majority of these fusion proteins (e.g., TNV/p28tev, p186Drev, Tat1-Rev2, Tat^8c, p17tev, or Ref) are the result of alternative splicing events, Tat-T/Vpt is produced upon programmed ribosomal frameshifting, and a Rev1-Vpu fusion protein is expressed due to a nucleotide polymorphism that is unique to certain HIV-1 clade A and C strains. A better understanding of the expression and activity of these non-canonical viral proteins will help to dissect their potential role in viral replication and reveal how HIV-1 optimized the coding potential of its genes. The goal of this review is to provide an overview of previously described HIV-1 fusion proteins and to summarize our current knowledge of their expression patterns and putative functions. PMID:28119676

  10. ORF7-encoded accessory protein 7a of feline infectious peritonitis virus as a counteragent against IFN-α-induced antiviral response.

    PubMed

    Dedeurwaerder, Annelike; Olyslaegers, Dominique A J; Desmarets, Lowiese M B; Roukaerts, Inge D M; Theuns, Sebastiaan; Nauwynck, Hans J

    2014-02-01

    The type I IFN-mediated immune response is the first line of antiviral defence. Coronaviruses, like many other viruses, have evolved mechanisms to evade this innate response, ensuring their survival. Several coronavirus accessory genes play a central role in these pathways, but for feline coronaviruses this has never to our knowledge been studied. As it has been demonstrated previously that ORF7 is essential for efficient replication in vitro and virulence in vivo of feline infectious peritonitis virus (FIPV), the role of this ORF in the evasion of the IFN-α antiviral response was investigated. Deletion of ORF7 from FIPV strain 79-1146 (FIPV-Δ7) rendered the virus more susceptible to IFN-α treatment. Given that ORF7 encodes two proteins, 7a and 7b, it was further explored which of these proteins is active in this mechanism. Providing 7a protein in trans rescued the mutant FIPV-Δ7 from IFN sensitivity, which was not achieved by addition of 7b protein. Nevertheless, addition of protein 7a to FIPV-Δ3Δ7, a FIPV mutant deleted in both ORF3 and ORF7, could no longer increase the replication capacity of this mutant in the presence of IFN. These results indicate that FIPV 7a protein is a type I IFN antagonist and protects the virus from the antiviral state induced by IFN, but it needs the presence of ORF3-encoded proteins to exert its antagonistic function.

  11. The ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signalling.

    PubMed

    Matthews, Krystal L; Coleman, Christopher M; van der Meer, Yvonne; Snijder, Eric J; Frieman, Matthew B

    2014-04-01

    The recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV), a betacoronavirus, is associated with severe pneumonia and renal failure. The environmental origin of MERS-CoV is as yet unknown; however, its genome sequence is closely related to those of two bat coronaviruses, named BtCoV-HKU4 and BtCoV-HKU5, which were derived from Chinese bat samples. A hallmark of highly pathogenic respiratory viruses is their ability to evade the innate immune response of the host. CoV accessory proteins, for example those from severe acute respiratory syndrome CoV (SARS-CoV), have been shown to block innate antiviral signalling pathways. MERS-CoV, similar to SARS-CoV, has been shown to inhibit type I IFN induction in a variety of cell types in vitro. We therefore hypothesized that MERS-CoV and the phylogenetically related BtCoV-HKU4 and BtCoV-HKU5 may encode proteins with similar capabilities. In this study, we have demonstrated that the ORF4b-encoded accessory protein (p4b) of MERS-CoV, BtCoV-HKU4 and BtCoV-HKU5 may indeed facilitate innate immune evasion by inhibiting the type I IFN and NF-κB signalling pathways. We also analysed the subcellular localization of p4b from MERS-CoV, BtCoV-HKU4 and BtCoV-HKU5 and demonstrated that all are localized to the nucleus.

  12. Antigenic homogeneity of male Müllerian gland (MG) secretory proteins of a caecilian amphibian with secretory proteins of the mammalian prostate gland and seminal vesicles: evidence for role of the caecilian MG as a male accessory reproductive gland.

    PubMed

    Radha, Arumugam; Sree, Sreesha; Faisal, Kunnathodi; Kumar, G Pradeep; Oommen, Oommen V; Akbarsha, Mohammad A

    2014-10-01

    Whereas in all other vertebrates the Müllerian ducts of genetic males are aborted during development, under the influence of Müllerian-inhibiting substance, in the caecilian amphibians they are retained as a pair of functional glands. It has long been speculated that the Müllerian gland might be the male accessory reproductive gland but there has been no direct evidence to this effect. The present study was undertaken to determine whether the caecilian Müllerian gland secretory proteins would bear antigenic similarity to secretory proteins of the prostate gland and/or the seminal vesicles of a mammal. The secretory proteins of the Müllerian gland of Ichthyophis tricolor were evaluated for cross-reactivity with antisera raised against rat ventral prostate and seminal vesicle secretory proteins, adopting SDS-PAGE, two-dimensional electrophoresis and immunoblot techniques. Indeed there was a cross-reaction of five Müllerian gland secretory protein fractions with prostatic protein antiserum and of three with seminal vesicle protein antiserum. A potential homology exists because in mammals the middle group of the prostate primordia is derived from a diverticulum of the Müllerian duct. Thus this study, by providing evidence for expression of prostatic and seminal vesicle proteins in the Müllerian gland, substantiates the point that in caecilians the Müllerian glands are the male accessory reproductive glands.

  13. Accessory mental foramen

    PubMed Central

    Balcioglu, Huseyin Avni; Kocaelli, Humeyra

    2009-01-01

    Context: Accessory mental foramen is a rare anatomical variation. Even so, in order to avoid neurovascular complications, particular attention should be paid to the possible occurrence of one or more accessory mental foramen during surgical procedures involving the mandible. Case report: A 3-dimensional computed tomography (3D-CT) scan of a female patient revealed an accessory mental foramen on the right side of her mandible. Conclusion: A 3D-CT scan should be obtained prior to mandibular surgeries so that the presence of accessory mental foramen can be detected, and so that the occurrence of a neurosensory disturbance or hemorrhage can be avoided. Although this anatomical variation is rare, it should be kept in mind that an accessory mental foramen may exist. PMID:22666714

  14. 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.

  15. 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.

  16. Remodeling of the Host Cell Plasma Membrane by HIV-1 Nef and Vpu: A Strategy to Ensure Viral Fitness and Persistence

    PubMed Central

    Sugden, Scott M.; Bego, Mariana G.; Pham, Tram N.Q.; Cohen, Éric A.

    2016-01-01

    The plasma membrane protects the cell from its surroundings and regulates cellular communication, homing, and metabolism. Not surprisingly, the composition of this membrane is highly controlled through the vesicular trafficking of proteins to and from the cell surface. As intracellular pathogens, most viruses exploit the host plasma membrane to promote viral replication while avoiding immune detection. This is particularly true for the enveloped human immunodeficiency virus (HIV), which assembles and obtains its lipid shell directly at the plasma membrane. HIV-1 encodes two proteins, negative factor (Nef) and viral protein U (Vpu), which function primarily by altering the quantity and localization of cell surface molecules to increase virus fitness despite host antiviral immune responses. These proteins are expressed at different stages in the HIV-1 life cycle and employ a variety of mechanisms to target both unique and redundant surface proteins, including the viral receptor CD4, host restriction factors, immunoreceptors, homing molecules, tetraspanins and membrane transporters. In this review, we discuss recent progress in the study of the Nef and Vpu targeting of host membrane proteins with an emphasis on how remodeling of the cell membrane allows HIV-1 to avoid host antiviral immune responses leading to the establishment of systemic and persistent infection. PMID:26950141

  17. Remodeling of the Host Cell Plasma Membrane by HIV-1 Nef and Vpu: A Strategy to Ensure Viral Fitness and Persistence.

    PubMed

    Sugden, Scott M; Bego, Mariana G; Pham, Tram N Q; Cohen, Éric A

    2016-03-03

    The plasma membrane protects the cell from its surroundings and regulates cellular communication, homing, and metabolism. Not surprisingly, the composition of this membrane is highly controlled through the vesicular trafficking of proteins to and from the cell surface. As intracellular pathogens, most viruses exploit the host plasma membrane to promote viral replication while avoiding immune detection. This is particularly true for the enveloped human immunodeficiency virus (HIV), which assembles and obtains its lipid shell directly at the plasma membrane. HIV-1 encodes two proteins, negative factor (Nef) and viral protein U (Vpu), which function primarily by altering the quantity and localization of cell surface molecules to increase virus fitness despite host antiviral immune responses. These proteins are expressed at different stages in the HIV-1 life cycle and employ a variety of mechanisms to target both unique and redundant surface proteins, including the viral receptor CD4, host restriction factors, immunoreceptors, homing molecules, tetraspanins and membrane transporters. In this review, we discuss recent progress in the study of the Nef and Vpu targeting of host membrane proteins with an emphasis on how remodeling of the cell membrane allows HIV-1 to avoid host antiviral immune responses leading to the establishment of systemic and persistent infection.

  18. Guanylate Binding Protein (GBP) 5 Is an Interferon-Inducible Inhibitor of HIV-1 Infectivity.

    PubMed

    Krapp, Christian; Hotter, Dominik; Gawanbacht, Ali; McLaren, Paul J; Kluge, Silvia F; Stürzel, Christina M; Mack, Katharina; Reith, Elisabeth; Engelhart, Susanne; Ciuffi, Angela; Hornung, Veit; Sauter, Daniel; Telenti, Amalio; Kirchhoff, Frank

    2016-04-13

    Guanylate binding proteins (GBPs) are an interferon (IFN)-inducible subfamily of guanosine triphosphatases (GTPases) with well-established activity against intracellular bacteria and parasites. Here we show that GBP5 potently restricts HIV-1 and other retroviruses. GBP5 is expressed in the primary target cells of HIV-1, where it impairs viral infectivity by interfering with the processing and virion incorporation of the viral envelope glycoprotein (Env). GBP5 levels in macrophages determine and inversely correlate with infectious HIV-1 yield over several orders of magnitude, which may explain the high donor variability in macrophage susceptibility to HIV. Antiviral activity requires Golgi localization of GBP5, but not its GTPase activity. Start codon mutations in the accessory vpu gene from macrophage-tropic HIV-1 strains conferred partial resistance to GBP5 inhibition by increasing Env expression. Our results identify GBP5 as an antiviral effector of the IFN response and may explain the increased frequency of defective vpu genes in primary HIV-1 strains.

  19. 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

  20. Accessory Breast Carcinoma

    PubMed Central

    Youn, Hyun Jo; Jung, Sung Hoo

    2009-01-01

    Summary Background Ectopic breast tissue usually develops along the mammary ridges, and the incidence has been reported to be 2–6% of the general population. Occurrence of primary carcinoma in ectopic breast tissue is rare. Case Report We report the case of 59-year-old woman with accessory breast carcinoma in her left axilla. Conclusion Because an accessory areola or nipple is often missing and awareness of physicians and patients about these unsuspicious masses is lacking, clinical diagnosis of accessory breast carcinoma is frequently delayed. Therefore, a mass along the ‘milk line’ should be examined carefully, and any suspicious lesions should be evaluated. PMID:20847887

  1. 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.

  2. Helping Hands for Budding Prospects: ENTH/ANTH/VHS Accessory Proteins in Endocytosis, Vacuolar Transport, and Secretion[W

    PubMed Central

    Zouhar, Jan; Sauer, Michael

    2014-01-01

    Coated vesicles provide a major mechanism for the transport of proteins through the endomembrane system of plants. Transport between the endoplasmic reticulum and the Golgi involves vesicles with COPI and COPII coats, whereas clathrin is the predominant coat in endocytosis and post-Golgi trafficking. Sorting of cargo, coat assembly, budding, and fission are all complex and tightly regulated processes that involve many proteins. The mechanisms and responsible factors are largely conserved in eukaryotes, and increasing organismal complexity tends to be associated with a greater numbers of individual family members. Among the key factors is the class of ENTH/ANTH/VHS domain-containing proteins, which link membrane subdomains, clathrin, and other adapter proteins involved in early steps of clathrin coated vesicle formation. More than 30 Arabidopsis thaliana proteins contain this domain, but their generally low sequence conservation has made functional classification difficult. Reports from the last two years have greatly expanded our knowledge of these proteins and suggest that ENTH/ANTH/VHS domain proteins are involved in various instances of clathrin-related endomembrane trafficking in plants. This review aims to summarize these new findings and discuss the broader context of clathrin-dependent plant vesicular transport. PMID:25415979

  3. Dual interaction of a geminivirus replication accessory factor with a viral replication protein and a plant cell cycle regulator.

    PubMed

    Settlage, S B; Miller, A B; Gruissem, W; Hanley-Bowdoin, L

    2001-01-20

    Geminiviruses replicate their small, single-stranded DNA genomes through double-stranded DNA intermediates in plant nuclei using host replication machinery. Like most dicot-infecting geminiviruses, tomato golden mosaic virus encodes a protein, AL3 or C3, that greatly enhances viral DNA accumulation through an unknown mechanism. Earlier studies showed that AL3 forms oligomers and interacts with the viral replication initiator AL1. Experiments reported here established that AL3 also interacts with a plant homolog of the mammalian tumor suppressor protein, retinoblastoma (pRb). Analysis of truncated AL3 proteins indicated that pRb and AL1 bind to similar regions of AL3, whereas AL3 oligomerization is dependent on a different region of the protein. Analysis of truncated AL1 proteins located the AL3-binding domain between AL1 amino acids 101 and 180 to a region that also includes the AL1 oligomerization domain and the catalytic site for initiation of viral DNA replication. Interestingly, the AL3-binding domain was fully contiguous with the domain that mediates AL1/pRb interactions. The potential significance of AL3/pRb binding and the coincidence of the domains responsible for AL3, AL1, and pRb interactions are discussed.

  4. Identifying the activation motif in the N-terminal of rainbow trout and zebrafish melanocortin-2 receptor accessory protein 1 (MRAP1) orthologs.

    PubMed

    Dores, Robert M; Liang, Liang; Hollmann, Rebecca E; Sandhu, Navdeep; Vijayan, Mathilakath M

    2016-08-01

    The activation of mammalian melanocortin-2 receptor (MC2R) orthologs is dependent on a four-amino acid activation motif (LDYL/I) located in the N-terminal of mammalian MRAP1 (melanocortin-2 receptor accessory protein). Previous alanine substitution analysis had shown that the Y residue in this motif appears to be the most important for mediating the activation of mammalian MC2R orthologs. Similar, but not identical amino acid motifs were detected in rainbow trout MRAP1 (YDYL) and zebrafish MRAP1 (YDYV). To determine the importance of these residues in the putative activation motifs, rainbow trout and zebrafish MRAP1 orthologs were individually co-expressed in CHO cells with rainbow trout MC2R, and the activation of this receptor with either the wild-type MRAP1 ortholog or alanine-substituted analogs of the two teleost MRAP1s was analyzed. Alanine substitutions at all four amino acid positions in rainbow trout MRAP1 blocked activation of the rainbow trout MC2R. Single alanine substitutions of the D and Y residues in rainbow trout and zebrafish MRAP1 indicate that these two residues play a significant role in the activation of rainbow trout MC2R. These observations indicate that there are subtle differences in the way that teleost and mammalian MRAPs are involved in the activation of their corresponding MC2R orthologs.

  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 early origin of melanocortin receptors, agouti-related peptide, agouti signalling peptide, and melanocortin receptor-accessory proteins, with emphasis on pufferfishes, elephant shark, lampreys, and amphioxus.

    PubMed

    Västermark, Ake; Schiöth, Helgi B

    2011-06-11

    There are conflicting theories about the evolution of melanocortin MC receptors while only few studies have addressed the evolution of agouti-related peptide (AgRP) and agouti signalling peptide (ASIP), which are antagonists at the melanocortin receptors (MCRs), or the melanocortin MC(2) receptor accessory proteins (MRAP1 and MRAP2). Previously we have cloned melanocortin MC receptors (MC(a) and MC(b)) genes in river lamprey and here we identify orthologues to these melanocortin MC receptor sequences in the sea lamprey. We investigate the putative presence of the melanocortin MC receptor genes in lancelet (amphioxus; Branchiostoma floridae) but we find it unlikely that such gene exists, due to a sharp drop in sequence similarity beyond sequence clusters of known receptors. We show the presence of AgRP and ASIP in elephant shark, a cartilaginous fish belonging to the subclass of Elasmobranchii. However, we do not find any of these genes in lamprey or lancelet after detailed analysis of both targeted and whole proteome regular expression scans. We found MRAP2, but not MRAP1, to be present in elephant shark and sea lamprey while Fugu (T. rubripes) has both genes. This study shows that the most ancient presence of these melanocortin-related sequences is found in elephant shark and lampreys considering the current available sequence data.

  7. DNA polymerase III accessory proteins. I. holA and holB encoding delta and delta'.

    PubMed

    Dong, Z; Onrust, R; Skangalis, M; O'Donnell, M

    1993-06-05

    The genes encoding the delta and delta' subunits of the 10-subunit Escherichia coli replicase, DNA polymerase III holoenzyme, have been identified and sequenced. The holA gene encoding delta is located downstream of rlpB at 15.2 min and predicts a 38.7 kda protein. The holB gene encoding delta' is located at 24.3 min and predicts a 36.9-kDa protein. Hence the delta and delta' subunits are unrelated proteins encoded by separate genes. The genes have been used to express and purify delta and delta' in quantity. The predicted amino acid sequence of delta' is homologous to the sequences of the tau and gamma subunits revealing a large amount of structural redundancy within the holoenzyme.

  8. Lipopolysaccharide (LPS)-binding protein and soluble CD14 function as accessory molecules for LPS-induced changes in endothelial barrier function, in vitro.

    PubMed Central

    Goldblum, S E; Brann, T W; Ding, X; Pugin, J; Tobias, P S

    1994-01-01

    Bacterial LPS induces endothelial cell (EC) injury both in vivo and in vitro. We studied the effect of Escherichia coli 0111:B4 LPS on movement of 14C-BSA across bovine pulmonary artery EC monolayers. In the presence of serum, a 6-h LPS exposure augmented (P < 0.001) transendothelial 14C-BSA flux compared with the media control at concentrations > or = 0.5 ng/ml, and LPS (10 ng/ml) exposures of > or = 2-h increased (P < 0.005) the flux. In the absence of serum, LPS concentrations of up to 10 micrograms/ml failed to increase 14C-BSA flux at 6 h. The addition of 10% serum increased EC sensitivity to the LPS stimulus by > 10,000-fold. LPS (10 ng/ml, 6 h) failed to increase 14C-BSA flux at serum concentrations < 0.5%, and maximum LPS-induced increments could be generated in the presence of > or = 2.5%. LPS-binding protein (LBP) and soluble CD14 (sCD14) could each satisfy this serum requirement; either anti-LBP or anti-CD14 antibody each totally blocked (P < 0.00005) the LPS-induced changes in endothelial barrier function. LPS-LBP had a more rapid onset than did LPS-sCD14. The LPS effect in the presence of both LBP and sCD14 exceeded the effect in the presence of either protein alone. These data suggest that LBP and sCD14 each independently functions as an accessory molecule for LPS presentation to the non-CD14-bearing endothelial surface. However, in the presence of serum both molecules are required. Images PMID:7509346

  9. Phylogenetic Insights into the Functional Relationship between Primate Lentiviral Reverse Transcriptase and Accessory Proteins Vpx/Vpr

    PubMed Central

    Sakai, Yosuke; Doi, Naoya; Miyazaki, Yasuyuki; Adachi, Akio; Nomaguchi, Masako

    2016-01-01

    The efficiency of reverse transcription to synthesize viral DNA in infected cells greatly influences replication kinetics of retroviruses. However, viral replication in non-dividing cells such as resting T cells and terminally differentiated macrophages is potently and kinetically restricted by a host antiviral factor designated SAMHD1 (sterile alpha motif and HD-domain containing protein 1). SAMHD1 reduces cellular deoxynucleoside triphosphate (dNTP) pools and affects viral reverse transcription step. Human immunodeficiency virus type 2 (HIV-2) and some simian immunodeficiency viruses (SIVs) have Vpx or Vpr to efficiently degrade SAMHD1. Interestingly, the reverse transcriptase (RT) derived from HIV-1 that encodes no anti-SAMHD1 proteins has been previously demonstrated to uniquely exhibit a high enzymatic activity. It is thus not irrational to assume that some viruses may have acquired or lost the specific RT property to better adapt themselves to the low dNTP environments confronted in non-dividing cells. This adaptation process may probably be correlated with the SAMHD1-antagonizing ability by viruses. In this report, we asked whether such adaptive events can be inferable from Vpx/Vpr and RT phylogenetic trees overlaid with SAMHD1-degrading capacity of Vpx/Vpr and with kinetic characteristics of RT. Resultant two trees showed substantially similar clustering patterns, and therefore suggested that the properties of RT and Vpx/Vpr can be linked. In other words, HIV/SIVs may possess their own RT proteins to adequately react to various dNTP circumstances in target cells. PMID:27803699

  10. Core Binding Factor β Protects HIV, Type 1 Accessory Protein Viral Infectivity Factor from MDM2-mediated Degradation.

    PubMed

    Matsui, Yusuke; Shindo, Keisuke; Nagata, Kayoko; Yoshinaga, Noriyoshi; Shirakawa, Kotaro; Kobayashi, Masayuki; Takaori-Kondo, Akifumi

    2016-11-25

    HIV, type 1 overcomes host restriction factor apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) proteins by organizing an E3 ubiquitin ligase complex together with viral infectivity factor (Vif) and a host transcription cofactor core binding factor β (CBFβ). CBFβ is essential for Vif to counteract APOBEC3 by enabling the recruitment of cullin 5 to the complex and increasing the steady-state level of Vif protein; however, the mechanisms by which CBFβ up-regulates Vif protein remains unclear. Because we have reported previously that mouse double minute 2 homolog (MDM2) is an E3 ligase for Vif, we hypothesized that CBFβ might protect Vif from MDM2-mediated degradation. Co-immunoprecipitation analyses showed that Vif mutants that do not bind to CBFβ preferentially interact with MDM2 and that overexpression of CBFβ disrupts the interaction between MDM2 and Vif. Knockdown of CBFβ reduced the steady-state level of Vif in MDM2-proficient cells but not in MDM2-null cells. Cycloheximide chase analyses revealed that Vif E88A/W89A, which does not interact with CBFβ, degraded faster than wild-type Vif in MDM2-proficient cells but not in MDM2-null cells, suggesting that Vif stabilization by CBFβ is mainly caused by impairing MDM2-mediated degradation. We identified Vif R93E as a Vif variant that does not bind to MDM2, and the virus with this substitution mutation was more resistant to APOBEC3G than the parental virus. Combinatory substitution of Vif residues required for CBFβ binding and MDM2 binding showed full recovery of Vif steady-state levels, supporting our hypothesis. Our data provide new insights into the mechanism of Vif augmentation by CBFβ.

  11. The neuron-specific interleukin-1 receptor accessory protein is required for homeostatic sleep and sleep responses to influenza viral challenge in mice.

    PubMed

    Davis, Christopher J; Dunbrasky, Danielle; Oonk, Marcella; Taishi, Ping; Opp, Mark R; Krueger, James M

    2015-07-01

    Interleukin-1β (IL1) is involved in sleep regulation and sleep responses induced by influenza virus. The IL1 receptor accessory protein (AcP) and an alternatively spliced isoform of AcP found primarily in neurons, AcPb, form part of the IL1 signaling complex. IL1-induced sleep responses depend on injection time. In rat cortex, both IL1 mRNA and AcPb mRNA peak at Zeitgeber Time (ZT) 0 then decline over the daylight hours. Sleep deprivation enhances cortical IL1 mRNA and AcPb mRNA levels, but not AcP mRNA. We used wild type (WT) and AcPb knockout (KO) mice and performed sleep deprivation between ZT10 and 20 or between ZT22 and 8 based on the time of day expression profiles of AcPb and IL1. We hypothesized that the magnitude of the responses to sleep loss would be strain- and time of day-dependent. In WT mice, NREMS and REMS rebounds occurred regardless of when they were deprived of sleep. In contrast, when AcPbKO mice were sleep deprived from ZT10 to 20 NREMS and REMS rebounds were absent. The AcPbKO mice expressed sleep rebound if sleep loss occurred from ZT22 to 8 although the NREMS responses were not as robust as those that occurred in WT mice. We also challenged mice with intranasal H1N1 influenza virus. WT mice exhibited the expected enhanced sleep responses. In contrast, the AcPbKO mice had less sleep after influenza challenge compared to their own baseline values and compared to WT mice. Body temperature and locomotor activity responses after viral challenge were lower and mortality was higher in AcPbKO than in WT mice. We conclude that neuron-specific AcPb plays a critical role in host defenses and sleep homeostasis.

  12. The Rcs stress response and accessory envelope proteins are required for de novo generation of cell shape in Escherichia coli.

    PubMed

    Ranjit, Dev K; Young, Kevin D

    2013-06-01

    Interactions with immune responses or exposure to certain antibiotics can remove the peptidoglycan wall of many Gram-negative bacteria. Though the spheroplasts thus created usually lyse, some may survive by resynthesizing their walls and shapes. Normally, bacterial morphology is generated by synthetic complexes directed by FtsZ and MreBCD or their homologues, but whether these classic systems can recreate morphology in the absence of a preexisting template is unknown. To address this question, we treated Escherichia coli with lysozyme to remove the peptidoglycan wall while leaving intact the inner and outer membranes and periplasm. The resulting lysozyme-induced (LI) spheroplasts recovered a rod shape after four to six generations. Recovery proceeded via a series of cell divisions that produced misshapen and branched intermediates before later progeny assumed a normal rod shape. Importantly, mutants defective in mounting the Rcs stress response and those lacking penicillin binding protein 1B (PBP1B) or LpoB could not divide or recover their cell shape but instead enlarged until they lysed. LI spheroplasts from mutants lacking the Lpp lipoprotein or PBP6 produced spherical daughter cells that did not recover a normal rod shape or that did so only after a significant delay. Thus, to regenerate normal morphology de novo, E. coli must supplement the classic FtsZ- and MreBCD-directed cell wall systems with activities that are otherwise dispensable for growth under normal laboratory conditions. The existence of these auxiliary mechanisms implies that they may be required for survival in natural environments, where bacterial walls can be damaged extensively or removed altogether.

  13. Kv4 Accessory Protein DPPX (DPP6) is a Critical Regulator of Membrane Excitability in Hippocampal CA1 Pyramidal Neurons

    PubMed Central

    Kim, Jinhyun; Nadal, Marcela S.; Clemens, Ann M.; Baron, Matthew; Jung, Sung-Cherl; Misumi, Yoshio; Rudy, Bernardo; Hoffman, Dax A.

    2008-01-01

    A-type K+ currents have unique kinetic and voltage-dependent properties that allow them to finely tune synaptic integration, action potential (AP) shape and firing patterns. In hippocampal CA1 pyramidal neurons, Kv4 channels make up the majority of the somatodendritic A-type current. Studies in heterologous expression systems have shown that Kv4 channels interact with transmembrane dipeptidyl-peptidase-like proteins (DPPLs) to regulate the surface trafficking and biophysical properties of Kv4 channels. To investigate the influence of DPPLs in a native system, we conducted voltage-clamp experiments in patches from CA1 pyramidal neurons expressing short-interfering RNA (siRNA) targeting the DPPL variant known to be expressed in hippocampal pyramidal neurons, DPPX (siDPPX). In accordance with heterologous studies, we found that DPPX downregulation in neurons resulted in depolarizing shifts of the steady-state inactivation and activation curves, a shallower conductance-voltage slope, slowed inactivation, and a delayed recovery from inactivation for A-type currents. We carried out current-clamp experiments to determine the physiological effect of the A-type current modifications by DPPX. Neurons expressing siDPPX exhibited a surprisingly large reduction in subthreshold excitability as measured by a decrease in input resistance, delayed time to AP onset, and an increased AP threshold. Suprathreshold DPPX downregulation resulted in slower AP rise and weaker repolarization. Computer simulations supported our experimental results and demonstrated how DPPX remodeling of A-channel properties can result in opposing sub- and suprathreshold effects on excitability. The Kv4 auxiliary subunit DPPX thus acts to increase neuronal responsiveness and enhance signal precision by advancing AP initiation and accelerating both the rise and repolarization of APs. PMID:18667548

  14. Accessory nerve palsy.

    PubMed

    Olarte, M; Adams, D

    1977-11-01

    After apparently uncomplicated excision of benign lesions in the posterior cervical triangle, two patients had shoulder pain. In one, neck pain and trapezius weakness were not prominent until one month after surgery. Inability to elevate the arm above the horizontal without externally rotating it, and prominent scapular displacement on arm abduction, but not on forward pushing movements, highlighted the trapezius dysfunction and differentiated it from serratus anterior weakness. Spinal accessory nerve lesions should be considered when minor surgical procedures, lymphadenitis, minor trauma, or tumours involved the posterior triangle of the neck.

  15. Structural Studies of Apo Nosl, an Accessory Protein of the Nitrous Oxide Reductase System: Insights from Structural Homology with MerB, a Mercury Resistance Protein

    SciTech Connect

    Taubner, Lara M.; McGuirl, Michele A.; Dooley, David M.; Copie, Valerie

    2006-09-19

    The formation of the unique catalytic tetranuclear copper cluster (CuZ) of nitrous oxide reductase, N2OR, requires the coexpression of a multiprotein assembly apparatus encoded by the nosDFYL operon. NosL, one of the proteins encoded by this transcript, is a 20 kDa lipoprotein of the periplasm that has been shown to bind copper(I), although its function has yet to be detemined. Cu(I) EXAFS data collected on the holo protein demonstrated that features of the copper binding site are consistent with a role for this protein as a metallochaperone, a class of metal ion transporters involved in metal resistance, homeostasis, and metallocluster biosynthesis. To test this hypothesis and to gain insight into other potential functional roles for this protein in the N2OR system, the three-dimensional solution structure of apo NosL has been solved by solution NMR methods. The structure of apo NosL consists of two relatively independent homologous domains that adopt an unusual topology.

  16. Torsion of Accessory Hepatic Lobe

    PubMed Central

    Natarajan, Saravanan; Jayasudha; Periasamy, Manikandhan; Rangasamy, Saminathan

    2017-01-01

    An accessory hepatic lobe is a rare congenital anomaly that can undergo torsion and present as an acute surgical emergency. A 5-year-old child admitted as acute abdomen, on laparotomy found to have torsion of accessory lobe of liver, is being reported. PMID:28082782

  17. Naturally occurring accessory gene mutations lead to persistent human immunodeficiency virus type 1 infection of CD4-positive T cells.

    PubMed Central

    Kishi, M; Zheng, Y H; Bahmani, M K; Tokunaga, K; Takahashi, H; Kakinuma, M; Lai, P K; Nonoyama, M; Luftig, R B; Ikuta, K

    1995-01-01

    Proviral DNA from cells surviving severe but transient cytopathic effects, mediated by infection with recombinant human immunodeficiency virus type 1 (HIV-1) carrying a single gene mutation at vif, vpr, or vpu, was characterized by use of HIV-1-specific primer pairs in a two-step PCR. Deletion mutations were detected in a region that spanned the vif and vpr open reading frames. Cloning and sequencing of the amplified DNA from this region revealed frequent large deletions in a limited number of nucleotide positions. Analyses of the deletions suggested that (i) genetic recombination, (ii) template-primer slippage, and (iii) misalignment of the growing point during reverse transcription of the HIV-1 genome might be the mechanisms that generated the mutations. Apart from the large deletions, smaller deletions that gave frameshift mutations in vif and/or vpr prevailed. In addition, cells infected with a triple mutant defective in vif, vpr, and vpu did not show any cytopathic effect. Thus, mutations generating multiple accessory gene defects during HIV-1 replication correlate with viral persistence and loss of cytopathogenicity. PMID:7494257

  18. CD155 on HIV-Infected Cells Is Not Modulated by HIV-1 Vpu and Nef but Synergizes with NKG2D Ligands to Trigger NK Cell Lysis of Autologous Primary HIV-Infected Cells.

    PubMed

    Davis, Zachary B; Sowrirajan, Bharatwaj; Cogswell, Andrew; Ward, Jeffery P; Planelles, Vicente; Barker, Edward

    2017-02-01

    Activation of primary CD4(+) T cells induces the CD155, but not the CD112 ligands for the natural killer (NK) cell activation receptor (aNKR) CD226 [DNAX accessory molecule-1 (DNAM-1)]. We hypothesize that HIV productively infects activated CD4(+) T cells and makes itself vulnerable to NK cell-mediated lysis when CD155 on infected T cells engages DNAM-1. The primary objective of this study is to determine whether CD155 alone or together with NKG2D ligands triggers autologous NK cell lysis of HIV-infected T cells and whether HIV modulates CD155. To determine whether HIV modulates this activation ligand, we infected "activated" CD4(+) T cells with HIV in the absence or presence of Nef and/or Vpu and determined by flow cytometry whether they modulated CD155. To determine if CD155 alone, or together with NKG2D ligands, triggered NK cell lysis of autologous HIV-infected T cells, we treated purified NK cells with DNAM-1 and/or NKG2D blocking antibodies before the addition of purified autologous HIV-infected cells in cytolytic assays. Finally, we determined whether DNAM-1 works together with NKG2D as an NK cell coactivation receptor (caNKR) or whether they work independently as aNKRs to induce an NK cell lytic response. We demonstrate that HIV and specifically Nef and/or Vpu do not modulate CD155 on infected primary T cells; and both CD155 and NKG2D ligands synergize as aNKRs to trigger NK cell lysis of the infected cell.

  19. Connecting Replication and Repair: YoaA, a Helicase-Related Protein, Promotes Azidothymidine Tolerance through Association with Chi, an Accessory Clamp Loader Protein.

    PubMed

    Brown, Laura T; Sutera, Vincent A; Zhou, Shen; Weitzel, Christopher S; Cheng, Yisha; Lovett, Susan T

    2015-11-01

    Elongating DNA polymerases frequently encounter lesions or structures that impede progress and require repair before DNA replication can be completed. Therefore, directing repair factors to a blocked fork, without interfering with normal replication, is important for proper cell function, and it is a process that is not well understood. To study this process, we have employed the chain-terminating nucleoside analog, 3' azidothymidine (AZT) and the E. coli genetic system, for which replication and repair factors have been well-defined. By using high-expression suppressor screens, we identified yoaA, encoding a putative helicase, and holC, encoding the Chi component of the replication clamp loader, as genes that promoted tolerance to AZT. YoaA is a putative Fe-S helicase in the XPD/RAD3 family for which orthologs can be found in most bacterial genomes; E. coli has a paralog to YoaA, DinG, which possesses 5' to 3' helicase activity and an Fe-S cluster essential to its activity. Mutants in yoaA are sensitive to AZT exposure; dinG mutations cause mild sensitivity to AZT and exacerbate the sensitivity of yoaA mutant strains. Suppression of AZT sensitivity by holC or yoaA was mutually codependent and we provide evidence here that YoaA and Chi physically interact. Interactions of Chi with single-strand DNA binding protein (SSB) and with Psi were required to aid AZT tolerance, as was the proofreading 3' exonuclease, DnaQ. Our studies suggest that repair is coupled to blocked replication through these interactions. We hypothesize that SSB, through Chi, recruits the YoaA helicase to replication gaps and that unwinding of the nascent strand promotes repair and AZT excision. This recruitment prevents the toxicity of helicase activity and aids the handoff of repair with replication factors, ensuring timely repair and resumption of replication.

  20. Connecting Replication and Repair: YoaA, a Helicase-Related Protein, Promotes Azidothymidine Tolerance through Association with Chi, an Accessory Clamp Loader Protein

    PubMed Central

    Brown, Laura T.; Sutera, Vincent A.; Zhou, Shen; Weitzel, Christopher S.; Cheng, Yisha; Lovett, Susan T.

    2015-01-01

    Elongating DNA polymerases frequently encounter lesions or structures that impede progress and require repair before DNA replication can be completed. Therefore, directing repair factors to a blocked fork, without interfering with normal replication, is important for proper cell function, and it is a process that is not well understood. To study this process, we have employed the chain-terminating nucleoside analog, 3’ azidothymidine (AZT) and the E. coli genetic system, for which replication and repair factors have been well-defined. By using high-expression suppressor screens, we identified yoaA, encoding a putative helicase, and holC, encoding the Chi component of the replication clamp loader, as genes that promoted tolerance to AZT. YoaA is a putative Fe-S helicase in the XPD/RAD3 family for which orthologs can be found in most bacterial genomes; E. coli has a paralog to YoaA, DinG, which possesses 5’ to 3’ helicase activity and an Fe-S cluster essential to its activity. Mutants in yoaA are sensitive to AZT exposure; dinG mutations cause mild sensitivity to AZT and exacerbate the sensitivity of yoaA mutant strains. Suppression of AZT sensitivity by holC or yoaA was mutually codependent and we provide evidence here that YoaA and Chi physically interact. Interactions of Chi with single-strand DNA binding protein (SSB) and with Psi were required to aid AZT tolerance, as was the proofreading 3’ exonuclease, DnaQ. Our studies suggest that repair is coupled to blocked replication through these interactions. We hypothesize that SSB, through Chi, recruits the YoaA helicase to replication gaps and that unwinding of the nascent strand promotes repair and AZT excision. This recruitment prevents the toxicity of helicase activity and aids the handoff of repair with replication factors, ensuring timely repair and resumption of replication. PMID:26544712

  1. 14 CFR 33.25 - Accessory attachments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Accessory attachments. 33.25 Section 33.25... STANDARDS: AIRCRAFT ENGINES Design and Construction; General § 33.25 Accessory attachments. The engine must operate properly with the accessory drive and mounting attachments loaded. Each engine accessory drive...

  2. Endoscopic Accessory Navicular Synchondrosis Fusion.

    PubMed

    Lui, Tun Hing

    2016-12-01

    The accessory navicular bone is one of the most common accessory ossicles of the foot. Fewer than 1% of accessory navicular bones are symptomatic, and most of these are type II accessory navicular bones. A separation of the synchondrosis is considered one of the main causes of pain. After an injury to the synchondrosis has resulted in a chondro-osseous disruption, the combined forces of tension and shear from the posterior tibial tendon and the foot aggravate the injury and prevent it from healing. Fusion of the synchondrosis is a logical surgical treatment option if the pain is recalcitrant to conservative measures. The purpose of this technical note is to report an endoscopic approach to achieve fusion. It has the advantages of better cosmesis, less scar pain, less risk of nonunion, and potential to examine the tibialis posterior tendon and the talonavicular joint.

  3. Accessory drive for a turbine engine

    SciTech Connect

    Brogdon, J.W.; Allen, K.D.; Barton, J.S.; Hicks, R.J.

    1987-02-03

    This patent describes, in combination: a radial flow turbine engine having a main shaft and a casing with air inlets open radially at one end, and an accessory drive comprising: an accessory housing positioned axially adjacent the one end of the turbine engine casing, a gear ring rotatably mounted within the accessory housing, means for mechanically drivingly connecting the gear ring to the turbine main shaft, the connecting means comprising a planetary gear arrangement contained in the accessory housing, the accessory housing having apertures open to the gear ring and circumferentially spaced from each other, at least one accessory having a driven gear, and means for mounting the at least one accessory to the accessory housing so that the accessory registers with one of the plurality of apertures and so that the gear ring meshes with the driven gear, wherein each aperture is adapted for connection with a separate accessory.

  4. Automobile accessories: Assessment and improvement

    SciTech Connect

    Jackson, M.

    1995-11-01

    With mandates and regulatory policies to meet both the California Air Resources Board (CARB) and the Partnership for a New Generation of Vehicles (PNGV), designing vehicles of the future will become a difficult task. As we look into the use of electric and hybrid vehicles, reduction of the required power demand by influential automobile components is necessary in order to obtain performance and range goals. Among those automobile components are accessories. Accessories have a profound impact on the range and mileage of future vehicles with limited amounts of energy or without power generating capabilities such as conventional vehicles. Careful assessment of major power consuming accessories helps us focus on those that need improvement and contributes to attainment of mileage and range goals for electric and hybrid vehicles.

  5. 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…

  6. Intrahepatic accessory spleen: imaging features.

    PubMed

    Izzo, Luciano; Caputo, Maria; Galati, Gaspare

    2004-06-01

    The authors present a case report of a 60-year-old man with a hepatic unknown mass. For diagnosis, they used ECO, CT (with and without contrast), MR (with and without contrast) and an ultrasound-assisted percutaneous lesion biopsy. Thus the mass-lesion in the liver appeared to be an intrahepatic accessory spleen in a patient afflicted with chronic hepatitis.

  7. 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 the engine oil system and the accessory system. (b) Electrical equipment subject to arcing or...

  8. The Fe-type nitrile hydratase from Comamonas testosteroni Ni1 does not require an activator accessory protein for expression in Escherichia coli

    SciTech Connect

    Kuhn, Misty L.; Martinez, Salette; Gumataotao, Natalie; Bornscheuer, Uwe; Liu, Dali; Holz, Richard C.

    2012-10-10

    We report herein the functional expression of an Fe-type nitrile hydratase (NHase) without the co-expression of an activator protein or the Escherichia coli chaperone proteins GroES/EL. Soluble protein was obtained when the {alpha}- and {beta}-subunit genes of the Fe-type NHase Comamonas testosteroni Ni1 (CtNHase) were synthesized with optimized E. coli codon usage and co-expressed. As a control, the Fe-type NHase from Rhodococcus equi TG328-2 (ReNHase) was expressed with (ReNHase{sup +Act}) and without (ReNHase{sup -Act}) its activator protein, establishing that expression of a fully functional, metallated ReNHase enzyme requires the co-expression of its activator protein, similar to all other Fe-type NHase enzymes reported to date, whereas the CtNHase does not. The X-ray crystal structure of CtNHase was determined to 2.4 {angstrom} resolution revealing an {alpha}{beta} heterodimer, similar to other Fe-type NHase enzymes, except for two important differences. First, two His residues reside in the CtNHase active site that are not observed in other Fe-type NHase enzymes and second, the active site Fe(III) ion resides at the bottom of a wide solvent exposed channel. The solvent exposed active site, along with the two active site histidine residues, are hypothesized to play a role in iron incorporation in the absence of an activator protein.

  9. The Fe-type nitrile hydratase from Comamonas testosteroni Ni1 does not require an activator accessory protein for expression in Escherichia coli.

    PubMed

    Kuhn, Misty L; Martinez, Salette; Gumataotao, Natalie; Bornscheuer, Uwe; Liu, Dali; Holz, Richard C

    2012-08-03

    We report herein the functional expression of an Fe-type nitrile hydratase (NHase) without the co-expression of an activator protein or the Escherichia coli chaperone proteins GroES/EL. Soluble protein was obtained when the α- and β-subunit genes of the Fe-type NHase Comamonas testosteroni Ni1 (CtNHase) were synthesized with optimized E. coli codon usage and co-expressed. As a control, the Fe-type NHase from Rhodococcus equi TG328-2 (ReNHase) was expressed with (ReNHase(+Act)) and without (ReNHase(-Act)) its activator protein, establishing that expression of a fully functional, metallated ReNHase enzyme requires the co-expression of its activator protein, similar to all other Fe-type NHase enzymes reported to date, whereas the CtNHase does not. The X-ray crystal structure of CtNHase was determined to 2.4Å resolution revealing an αβ heterodimer, similar to other Fe-type NHase enzymes, except for two important differences. First, two His residues reside in the CtNHase active site that are not observed in other Fe-type NHase enzymes and second, the active site Fe(III) ion resides at the bottom of a wide solvent exposed channel. The solvent exposed active site, along with the two active site histidine residues, are hypothesized to play a role in iron incorporation in the absence of an activator protein.

  10. Equine Tetherin Blocks Retrovirus Release and Its Activity Is Antagonized by Equine Infectious Anemia Virus Envelope Protein

    PubMed Central

    Yin, Xin; Hu, Zhe; Gu, Qinyong; Wu, Xingliang; Zheng, Yong-Hui; Wei, Ping

    2014-01-01

    Human tetherin is a host restriction factor that inhibits replication of enveloped viruses by blocking viral release. Tetherin has an unusual topology that includes an N-terminal cytoplasmic tail, a single transmembrane domain, an extracellular domain, and a C-terminal glycosylphosphatidylinositol anchor. Tetherin is not well conserved across species, so it inhibits viral replication in a species-specific manner. Thus, studies of tetherin activities from different species provide an important tool for understanding its antiviral mechanism. Here, we report cloning of equine tetherin and characterization of its antiviral activity. Equine tetherin shares 53%, 40%, 36%, and 34% amino acid sequence identity with feline, human, simian, and murine tetherins, respectively. Like the feline tetherin, equine tetherin has a shorter N-terminal domain than human tetherin. Equine tetherin is localized on the cell surface and strongly blocks human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), and equine infectious anemia virus (EIAV) release from virus-producing cells. The antiviral activity of equine tetherin is neutralized by EIAV envelope protein, but not by the HIV-1 accessory protein Vpu, which is a human tetherin antagonist, and EIAV envelope protein does not counteract human tetherin. These results shed new light on our understanding of the species-specific tetherin antiviral mechanism. PMID:24227834

  11. The specificity of association of the IgD molecule with the accessory proteins BAP31/BAP29 lies in the IgD transmembrane sequence.

    PubMed

    Adachi, T; Schamel, W W; Kim, K M; Watanabe, T; Becker, B; Nielsen, P J; Reth, M

    1996-04-01

    Mature B cells co-express on their cell surface two classes of antigen receptor, the IgM and IgD immunoglobulins. The structural and functional differences between the two receptor classes are poorly understood. Recently two proteins of 29 and 31 kDa (BAP29 and BAP31) have been described that are preferentially associated with membrane IgD but only weakly with membrane IgM. We describe here the cloning of full-length murine and human BAP31 cDNAs encoding proteins of 245 and 246 amino acids respectively. The two BAP31 proteins are 95% identical. The BAP31 gene is ubiquitously expressed in murine tissues and is located on the X chromosome in both mouse and man. The murine BAP31 protein has 43% sequence identity to murine BAP29. Both proteins have a hydrophobic N-terminus and an alpha-helical C-terminus which ends with a KKXX motif implicated in vesicular transport. By a mutational analysis we have identified amino acids in the transmembrane sequence of the delta m chain that are critical for binding to BAP31/BAP29. A structural model of the BAPs and their potential functions are discussed.

  12. The gene encoding the VP16-accessory protein HCF (HCFC1) resides in human Xq28 and is highly expressed in fetal tissues and the adult kidney

    SciTech Connect

    Wilson, A.C.; Herr, W.; Parrish, J.E.; Massa, H.F.

    1995-01-20

    After herpes simplex virus (HSV) infection, the viral regulatory protein VP16 activates transcription of the HSV immediate-early promoters by directing complex formation with two cellular proteins, the POU-homeodomain transcription factor Oct-1 and the host cell factor HCF. The function of HCF in uninfected cells is unknown. Here we show by fluorescence in situ hybridization and somatic cell hybrid analysis that the gene encoding human HCF, HCFC1, maps to the q28 region of the X chromosome. Yeast artificial chromosome and cosmid mapping localizes the HCFC1 gene within 100 kb distal of the renal vasopressin type-2 receptor (V2R) gene and adjacent to the renin-binding protein gene (RENBP). The HCFC1 gene is apparently unique. HCF transcripts and protein are most abundant in fetal and placental tissues and cell lines, suggesting a role in cell proliferation. In adults, HCF protein is abundant in the kidney, but not in the brain, a site of latent HSV infection and where HCF levels may influence progression of HSV infection. 42 refs., 3 figs.

  13. Locally vascularized pelvic accessory spleen.

    PubMed

    Iorio, F; Frantellizzi, V; Drudi, Francesco M; Maghella, F; Liberatore, M

    2016-01-01

    Polysplenism and accessory spleen are congenital, usually asymptomatic anomalies. A rare case of polysplenism with ectopic spleen in pelvis of a 67-year-old, Caucasian female is reported here. A transvaginal ultrasound found a soft well-defined homogeneous and vascularized mass in the left pelvis. Patient underwent MRI evaluation and contrast-CT abdominal scan: images with parenchymal aspect, similar to spleen were obtained. Abdominal scintigraphy with 99mTc-albumin nanocolloid was performed and pelvic region was studied with planar scans and SPECT. The results showed the presence of an uptake area of the radiopharmaceutical in the pelvis, while the spleen was normally visualized. These findings confirmed the presence of an accessory spleen with an artery originated from the aorta and a vein that joined with the superior mesenteric vein. To our knowledge, in the literature, there is just only one case of a true ectopic, locally vascularized spleen in the pelvis.

  14. Cas13b Is a Type VI-B CRISPR-Associated RNA-Guided RNase Differentially Regulated by Accessory Proteins Csx27 and Csx28.

    PubMed

    Smargon, Aaron A; Cox, David B T; Pyzocha, Neena K; Zheng, Kaijie; Slaymaker, Ian M; Gootenberg, Jonathan S; Abudayyeh, Omar A; Essletzbichler, Patrick; Shmakov, Sergey; Makarova, Kira S; Koonin, Eugene V; Zhang, Feng

    2017-02-16

    CRISPR-Cas adaptive immune systems defend microbes against foreign nucleic acids via RNA-guided endonucleases. Using a computational sequence database mining approach, we identify two class 2 CRISPR-Cas systems (subtype VI-B) that lack Cas1 and Cas2 and encompass a single large effector protein, Cas13b, along with one of two previously uncharacterized associated proteins, Csx27 and Csx28. We establish that these CRISPR-Cas systems can achieve RNA interference when heterologously expressed. Through a combination of biochemical and genetic experiments, we show that Cas13b processes its own CRISPR array with short and long direct repeats, cleaves target RNA, and exhibits collateral RNase activity. Using an E. coli essential gene screen, we demonstrate that Cas13b has a double-sided protospacer-flanking sequence and elucidate RNA secondary structure requirements for targeting. We also find that Csx27 represses, whereas Csx28 enhances, Cas13b-mediated RNA interference. Characterization of these CRISPR systems creates opportunities to develop tools to manipulate and monitor cellular transcripts.

  15. Engine starter and accessory drive system

    SciTech Connect

    Stockton, T.R.

    1986-10-07

    An engine starter and accessory drive system is described which consists of: an accessory drive means; a planetary gearset having a sun gear driveably connected to the accessory drive means, a ring gear, a carrier and planet pinions rotatably mounted on the carrier, fixed to the engine crankshaft, meshing with the sun gear and with the ring gear; means for holding the ring gear against rotation; and a starter motor and first clutch means for providing a one-way driving connection between the motor and the accessory drive means.

  16. FRACTIONATION OF PLASMA GLOBULIN FOR PROTHROMBIN, THROMBOKINASE, AND ACCESSORY THROMBOPLASTIN

    PubMed Central

    Milstone, J. H.

    1951-01-01

    1. Crude globulin from more than 1,000 liters of citrated bovine plasma has been used in developing a procedure for moderately large scale separation of clotting factors. Fraction A, prothrombin, kinase, and thrombin fractions were prepared. Fraction A contained both kinase and accessory thromboplastin, the latter predominating when fraction A was diluted. 2. When prothrombin was activated by kinase, the rate of thrombin production was enhanced by the addition of platelets, or brain lipid, or dilute fraction A. These accessory thromboplastins caused this acceleration only when calcium chloride was added. Even with calcium, they were not effective unless kinase was present. 3. In contrast, the action of kinase was not entirely dependent on either ionic calcium or accessory thromboplastin. The concentrated kinase fraction activated prothrombin in the presence of excess oxalate. Although kinase often contaminates highly purified thrombins, it is probably distinct from thrombin. The ratio of kinase to thrombin was 100 times as great in the kinase fraction as in the thrombin fraction. 4. The kinase fraction, diluted 45,000-fold, to protein-nitrogen concentrations as low as 0.02 microgram per ml., accelerated the conversion of crude prokinase in three-stage tests. 5. The findings are consistent with the following concept of the basic enzymatic mechanism: See PDF for Structure It is now added that calcium and accessory thromboplastin exert their effects by impinging on the basic mechanism, in a chemically secondary or indirect manner. PMID:14873922

  17. Advanced Accessory Power Supply Topologies

    SciTech Connect

    Marlino, L.D.

    2010-06-15

    This Cooperative Research and Development Agreement (CRADA) began December 8, 2000 and ended September 30, 2009. The total funding provided by the Participant (General Motors Advanced Technology Vehicles [GM]) during the course of the CRADA totaled $1.2M enabling the Contractor (UT-Battelle, LLC [Oak Ridge National Laboratory, a.k.a. ORNL]) to contribute significantly to the joint project. The initial task was to work with GM on the feasibility of developing their conceptual approach of modifying major components of the existing traction inverter/drive to develop low cost, robust, accessory power. Two alternate methods for implementation were suggested by ORNL and both were proven successful through simulations and then extensive testing of prototypes designed and fabricated during the project. This validated the GM overall concept. Moreover, three joint U.S. patents were issued and subsequently licensed by GM. After successfully fulfilling the initial objective, the direction and duration of the CRADA was modified and GM provided funding for two additional tasks. The first new task was to provide the basic development for implementing a cascaded inverter technology into hybrid vehicles (including plug-in hybrid, fuel cell, and electric). The second new task was to continue the basic development for implementing inverter and converter topologies and new technology assessments for hybrid vehicle applications. Additionally, this task was to address the use of high temperature components in drive systems. Under this CRADA, ORNL conducted further research based on GM’s idea of using the motor magnetic core and windings to produce bidirectional accessory power supply that is nongalvanically coupled to the terminals of the high voltage dc-link battery of hybrid vehicles. In order not to interfere with the motor’s torque, ORNL suggested to use the zero-sequence, highfrequency harmonics carried by the main fundamental motor current for producing the accessory power

  18. Kv4.2 and accessory dipeptidyl peptidase-like protein 10 (DPP10) subunit preferentially form a 4:2 (Kv4.2:DPP10) channel complex.

    PubMed

    Kitazawa, Masahiro; Kubo, Yoshihiro; Nakajo, Koichi

    2015-09-11

    Kv4 is a member of the voltage-gated K(+) channel family and forms a complex with various accessory subunits. Dipeptidyl aminopeptidase-like protein (DPP) is one of the auxiliary subunits for the Kv4 channel. Although DPP has been well characterized and is known to increase the current amplitude and accelerate the inactivation and recovery from inactivation of Kv4 current, it remains to be determined how many DPPs bind to one Kv4 channel. To examine whether the expression level of DPP changes the biophysical properties of Kv4, we expressed Kv4.2 and DPP10 in different ratios in Xenopus oocytes and analyzed the currents under two-electrode voltage clamp. The current amplitude and the speed of recovery from inactivation of Kv4.2 changed depending on the co-expression level of DPP10. This raised the possibility that the stoichiometry of the Kv4.2-DPP10 complex is variable and affects the biophysical properties of Kv4.2. We next determined the stoichiometry of DPP10 alone by subunit counting using single-molecule imaging. Approximately 70% of the DPP10 formed dimers in the plasma membrane, and the rest existed as monomers in the absence of Kv4.2. We next determined the stoichiometry of the Kv4.2-DPP10 complex; Kv4.2-mCherry and mEGFP-DPP10 were co-expressed in different ratios and the stoichiometries of Kv4.2-DPP10 complexes were evaluated by the subunit counting method. The stoichiometry of the Kv4.2-DPP10 complex was variable depending on the relative expression level of each subunit, with a preference for 4:2 stoichiometry. This preference may come from the bulky dimeric structure of the extracellular domain of DPP10.

  19. Extracranial spinal accessory nerve injury.

    PubMed

    Donner, T R; Kline, D G

    1993-06-01

    Eighty-three consecutive patients with extracranial accessory nerve injury seen over a 12-year period are reviewed. The most common etiology was iatrogenic injury to the nerve at the time of previous surgery. Such operations were usually minor in nature and often related to lymph node or benign tumor removal. Examination usually distinguished winging due to trapezius weakness from that of serratus anterior palsy. Trapezius weakness was seen in all cases. Sternocleidomastoid weakness was unusual. Patients with accessory palsy were evaluated by both clinical and electromyographic studies. Patients who exhibited no clinical or electrical evidence of regeneration were operated on (44 cases). Based on intraoperative nerve action potential studies, 8 lesions in continuity had neurolysis alone. Resection with repair either by end-to-end suture or by grafts was necessary in 31 cases. One case had suture removed from nerve, two had nerve placed into target muscle, and two had more proximal neurotization. Function was usually improved in both operative and nonoperative patients. Related anatomy is discussed.

  20. 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....

  1. 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....

  2. 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....

  3. 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....

  4. 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....

  5. Coevolution of the ATPase ClpV, the sheath proteins TssB and TssC, and the accessory protein TagJ/HsiE1 distinguishes type VI secretion classes.

    PubMed

    Förster, Andreas; Planamente, Sara; Manoli, Eleni; Lossi, Nadine S; Freemont, Paul S; Filloux, Alain

    2014-11-21

    The type VI secretion system (T6SS) is a bacterial nanomachine for the transport of effector molecules into prokaryotic and eukaryotic cells. It involves the assembly of a tubular structure composed of TssB and TssC that is similar to the tail sheath of bacteriophages. The sheath contracts to provide the energy needed for effector delivery. The AAA(+) ATPase ClpV disassembles the contracted sheath, which resets the systems for reassembly of an extended sheath that is ready to fire again. This mechanism is crucial for T6SS function. In Vibrio cholerae, ClpV binds the N terminus of TssC within a hydrophobic groove. In this study, we resolved the crystal structure of the N-terminal domain of Pseudomonas aeruginosa ClpV1 and observed structural alterations in the hydrophobic groove. The modification in the ClpV1 groove is matched by a change in the N terminus of TssC, suggesting the existence of distinct T6SS classes. An accessory T6SS component, TagJ/HsiE, exists predominantly in one of the classes. Using bacterial two-hybrid approaches, we showed that the P. aeruginosa homolog HsiE1 interacts strongly with ClpV1. We then resolved the crystal structure of HsiE1 in complex with the N terminus of HsiB1, a TssB homolog and component of the contractile sheath. Phylogenetic analysis confirmed that these differences distinguish T6SS classes that resulted from a functional co-evolution between TssB, TssC, TagJ/HsiE, and ClpV. The interaction of TagJ/HsiE with the sheath as well as with ClpV suggests an alternative mode of disassembly in which HsiE recruits the ATPase to the sheath.

  6. Coevolution of the ATPase ClpV, the Sheath Proteins TssB and TssC, and the Accessory Protein TagJ/HsiE1 Distinguishes Type VI Secretion Classes*

    PubMed Central

    Förster, Andreas; Planamente, Sara; Manoli, Eleni; Lossi, Nadine S.; Freemont, Paul S.; Filloux, Alain

    2014-01-01

    The type VI secretion system (T6SS) is a bacterial nanomachine for the transport of effector molecules into prokaryotic and eukaryotic cells. It involves the assembly of a tubular structure composed of TssB and TssC that is similar to the tail sheath of bacteriophages. The sheath contracts to provide the energy needed for effector delivery. The AAA+ ATPase ClpV disassembles the contracted sheath, which resets the systems for reassembly of an extended sheath that is ready to fire again. This mechanism is crucial for T6SS function. In Vibrio cholerae, ClpV binds the N terminus of TssC within a hydrophobic groove. In this study, we resolved the crystal structure of the N-terminal domain of Pseudomonas aeruginosa ClpV1 and observed structural alterations in the hydrophobic groove. The modification in the ClpV1 groove is matched by a change in the N terminus of TssC, suggesting the existence of distinct T6SS classes. An accessory T6SS component, TagJ/HsiE, exists predominantly in one of the classes. Using bacterial two-hybrid approaches, we showed that the P. aeruginosa homolog HsiE1 interacts strongly with ClpV1. We then resolved the crystal structure of HsiE1 in complex with the N terminus of HsiB1, a TssB homolog and component of the contractile sheath. Phylogenetic analysis confirmed that these differences distinguish T6SS classes that resulted from a functional co-evolution between TssB, TssC, TagJ/HsiE, and ClpV. The interaction of TagJ/HsiE with the sheath as well as with ClpV suggests an alternative mode of disassembly in which HsiE recruits the ATPase to the sheath. PMID:25305017

  7. Normal Variants: Accessory Muscles About the Ankle.

    PubMed

    Cheung, Yvonne

    2017-02-01

    Accessory muscles around the ankle are commonly encountered as incidental findings on cross-sectional imaging. Mostly asymptomatic, accessory muscles sometimes mimic mass lesions. They have been implicated as the cause of tarsal tunnel syndrome, impingement of surrounding structures, and chronic pain. Distinguishing these muscles can be challenging, because some travel along a similar path. This article describes these accessory muscles in detail, including their relationships to the aponeurosis of the lower leg. An imaging algorithm is proposed to aid in identification of these muscles, providing a valuable tool in diagnostic accuracy and subsequent patient management.

  8. 19 CFR 10.456 - Accessories, spare parts or tools.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Accessories, spare parts or tools. 10.456 Section... Trade Agreement Rules of Origin § 10.456 Accessories, spare parts or tools. Accessories, spare parts or tools that form part of the good's standard accessories, spare parts or tools and are delivered with...

  9. The Accessory Genome of Pseudomonas aeruginosa

    PubMed Central

    Kung, Vanderlene L.; Ozer, Egon A.; Hauser, Alan R.

    2010-01-01

    Summary: Pseudomonas aeruginosa strains exhibit significant variability in pathogenicity and ecological flexibility. Such interstrain differences reflect the dynamic nature of the P. aeruginosa genome, which is composed of a relatively invariable “core genome” and a highly variable “accessory genome.” Here we review the major classes of genetic elements comprising the P. aeruginosa accessory genome and highlight emerging themes in the acquisition and functional importance of these elements. Although the precise phenotypes endowed by the majority of the P. aeruginosa accessory genome have yet to be determined, rapid progress is being made, and a clearer understanding of the role of the P. aeruginosa accessory genome in ecology and infection is emerging. PMID:21119020

  10. Nef proteins from simian immunodeficiency viruses are tetherin antagonists

    PubMed Central

    Zhang, Fengwen; Wilson, Sam J.; Langford, Wilmina; Virgen, Beatriz; Gregory, Devon; Johnson, Marc; Munch, Jan; Kirchhoff, Frank; Bieniasz, Paul D.; Hatziioannou, Theodora

    2010-01-01

    The tetherin/BST2/CD317 protein blocks the release of HIV-1 and other enveloped viruses by inducing tethering of nascent particles to infected cell surfaces. The HIV-1 Vpu protein antagonizes the antiviral activity of human but not monkey tetherins and many simian immunodeficiency viruses (SIVs) do not encode Vpu. Here, we show that the apparently ‘missing’ anti-tetherin activity in SIVs has been acquired by several SIV Nef proteins. Specifically, SIVMAC/SIVSMM, SIVAGM and SIVBLU Nef proteins can suppress tetherin activity. Notably, tetherin antagonism by SIV Nef proteins is species-specific, is genetically separable from other Nef activities and is most evident with simian rather than human tetherin proteins. Accordingly, a critical determinant of sensitivity to SIVMAC Nef in the tetherin cytoplasmic tail is variable in nonhuman primate tetherins and deleted in human tetherin, likely due to selective pressures imposed by viral antagonists, perhaps including Nef proteins. PMID:19501037

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  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...

  18. 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...

  19. 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...

  20. 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...

  1. Smallpox vaccination techniques. 2. Accessories and aftercare.

    PubMed

    Baxby, Derrick

    2003-03-28

    The various accessories used for smallpox vaccination are surveyed. These included modified vaccination instruments and various other items which facilitated the procedure, containers for preservation and transport of vaccine, sterilising equipment, aids to interpretation and recording, and a variety of skin preparations and dressings. Three phases can be discerned in the development and use of such items and procedures. Initially, in the pre-bacteriological era, there was little need for accessory equipment apart from the means of preserving and transporting vaccine. Later, particularly by the end of the 19th century, the importance of aseptic and antiseptic procedures was realised, use was made of more traumatic vaccination techniques and glass capillaries became the standard method for preservation and transport. All this led to the increasing availability of a wide range of accessories, particularly of skin preparations and dressings. Finally, from about 1930, it was appreciated that skin preparation and dressings were often unnecessary, and could be counter-productive. So, although accessories for this were still available their use was very much reduced. In some respects the use of accessories during this last phase, based on scientific analysis was a return to the earliest, 'pre-scientific', era.

  2. The Balance between Recombination Enzymes and Accessory Replicative Helicases in Facilitating Genome Duplication

    PubMed Central

    Syeda, Aisha H.; Atkinson, John; Lloyd, Robert G.; McGlynn, Peter

    2016-01-01

    Accessory replicative helicases aid the primary replicative helicase in duplicating protein-bound DNA, especially transcribed DNA. Recombination enzymes also aid genome duplication by facilitating the repair of DNA lesions via strand exchange and also processing of blocked fork DNA to generate structures onto which the replisome can be reloaded. There is significant interplay between accessory helicases and recombination enzymes in both bacteria and lower eukaryotes but how these replication repair systems interact to ensure efficient genome duplication remains unclear. Here, we demonstrate that the DNA content defects of Escherichia coli cells lacking the strand exchange protein RecA are driven primarily by conflicts between replication and transcription, as is the case in cells lacking the accessory helicase Rep. However, in contrast to Rep, neither RecA nor RecBCD, the helicase/exonuclease that loads RecA onto dsDNA ends, is important for maintaining rapid chromosome duplication. Furthermore, RecA and RecBCD together can sustain viability in the absence of accessory replicative helicases but only when transcriptional barriers to replication are suppressed by an RNA polymerase mutation. Our data indicate that the minimisation of replisome pausing by accessory helicases has a more significant impact on successful completion of chromosome duplication than recombination-directed fork repair. PMID:27483323

  3. 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.

  4. Segregated pathways to the vomeronasal amygdala: differential projections from the anterior and posterior divisions of the accessory olfactory bulb.

    PubMed

    Mohedano-Moriano, Alicia; Pro-Sistiaga, Palma; Ubeda-Bañón, Isabel; Crespo, Carlos; Insausti, Ricardo; Martinez-Marcos, Alino

    2007-04-01

    Apically and basally located receptor neurons in the vomeronasal sensory epithelium express G(i2 alpha)- and G(o alpha)-proteins, V1R and V2R vomeronasal receptors, project to the anterior and posterior accessory olfactory bulb and respond to different stimuli, respectively. The extent to which secondary projections from the two portions of the accessory olfactory bulb are convergent in the vomeronasal amygdala is controversial. This issue is addressed by using anterograde and retrograde tract-tracing methods in rats including electron microscopy. Injections of dextran-amines, Fluoro Gold, cholera toxin-B subunit and Fast Blue were delivered to the anterior and posterior accessory olfactory bulb, bed nucleus of the stria terminalis, dorsal anterior amygdala and bed nucleus of the accessory olfactory tract/anteroventral medial amygdaloid nucleus. We have demonstrated that, apart from common vomeronasal-recipient areas, only the anterior accessory olfactory bulb projects to the bed nucleus of the stria terminalis, medial division, posteromedial part, and only the posterior accessory olfactory bulb projects to the dorsal anterior amygdala and deep cell layers of the bed nucleus of the accessory olfactory tract and the anteroventral medial amygdaloid nucleus. These results provide evidence that, excluding areas of convergence, the V1R and V2R vomeronasal pathways project to specific areas of the amygdala. These two vomeronasal subsystems are therefore anatomically and functionally separated in the telencephalon.

  5. 46 CFR 169.671 - Accessories.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Accessories. 169.671 Section 169.671 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Machinery and Electrical Electrical Installations Operating at Potentials of Less Than 50 Volts on Vessels of Less Than...

  6. 46 CFR 169.671 - Accessories.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Accessories. 169.671 Section 169.671 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Machinery and Electrical Electrical Installations Operating at Potentials of Less Than 50 Volts on Vessels of Less Than...

  7. 46 CFR 169.671 - Accessories.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Accessories. 169.671 Section 169.671 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Machinery and Electrical Electrical Installations Operating at Potentials of Less Than 50 Volts on Vessels of Less Than...

  8. 46 CFR 169.671 - Accessories.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Accessories. 169.671 Section 169.671 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Machinery and Electrical Electrical Installations Operating at Potentials of Less Than 50 Volts on Vessels of Less Than...

  9. 14 CFR 23.1163 - Powerplant accessories.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Have torque limiting means on all accessory drives in order to prevent the torque limits established... approved as part of the powerplant driving the gearbox must— (1) Have torque limiting means to prevent the torque limits established for the affected drive from being exceeded; (2) Use the provisions on...

  10. 14 CFR 23.1163 - Powerplant accessories.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) Have torque limiting means on all accessory drives in order to prevent the torque limits established... approved as part of the powerplant driving the gearbox must— (1) Have torque limiting means to prevent the torque limits established for the affected drive from being exceeded; (2) Use the provisions on...

  11. 14 CFR 23.1163 - Powerplant accessories.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) Have torque limiting means on all accessory drives in order to prevent the torque limits established... approved as part of the powerplant driving the gearbox must— (1) Have torque limiting means to prevent the torque limits established for the affected drive from being exceeded; (2) Use the provisions on...

  12. 14 CFR 23.1163 - Powerplant accessories.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) Have torque limiting means on all accessory drives in order to prevent the torque limits established... approved as part of the powerplant driving the gearbox must— (1) Have torque limiting means to prevent the torque limits established for the affected drive from being exceeded; (2) Use the provisions on...

  13. 14 CFR 23.1163 - Powerplant accessories.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) Have torque limiting means on all accessory drives in order to prevent the torque limits established... approved as part of the powerplant driving the gearbox must— (1) Have torque limiting means to prevent the torque limits established for the affected drive from being exceeded; (2) Use the provisions on...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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.

  20. Home Economics Careers in Apparel and Accessories.

    ERIC Educational Resources Information Center

    Texas Education Agency, Austin. Dept. of Occupational Education and Technology.

    This course of study on careers in apparel and accessories is one of a series on home economics careers designed to assist teacher-coordinators in Texas in promotion and/or teaching home economics cooperative education programs. The course of study consists of (1) an overview and job description, (2) a job analysis, (3) a course outline, (4)…

  1. 46 CFR 169.671 - Accessories.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Accessories. 169.671 Section 169.671 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Machinery and Electrical Electrical Installations Operating at Potentials of Less Than 50 Volts on Vessels of Less Than...

  2. 21 CFR 878.4700 - Surgical microscope and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Surgical microscope and accessories. 878.4700 Section 878.4700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... microscope and accessories. (a) Identification. A surgical microscope and accessories is an AC-powered...

  3. 21 CFR 878.4700 - Surgical microscope and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Surgical microscope and accessories. 878.4700 Section 878.4700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... microscope and accessories. (a) Identification. A surgical microscope and accessories is an AC-powered...

  4. 21 CFR 878.4700 - Surgical microscope and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Surgical microscope and accessories. 878.4700 Section 878.4700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... microscope and accessories. (a) Identification. A surgical microscope and accessories is an AC-powered...

  5. 21 CFR 878.4700 - Surgical microscope and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Surgical microscope and accessories. 878.4700 Section 878.4700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... microscope and accessories. (a) Identification. A surgical microscope and accessories is an AC-powered...

  6. 21 CFR 876.5540 - Blood access device and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Blood access device and accessories. 876.5540... (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5540 Blood access device and accessories. (a) Identification. A blood access device and accessories is a device intended...

  7. 21 CFR 876.5540 - Blood access device and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Blood access device and accessories. 876.5540... (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5540 Blood access device and accessories. (a) Identification. A blood access device and accessories is a device intended...

  8. 21 CFR 876.5540 - Blood access device and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Blood access device and accessories. 876.5540... (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5540 Blood access device and accessories. (a) Identification. A blood access device and accessories is a device intended...

  9. 21 CFR 876.5540 - Blood access device and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Blood access device and accessories. 876.5540... (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5540 Blood access device and accessories. (a) Identification. A blood access device and accessories is a device intended...

  10. 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...

  11. 19 CFR 10.600 - Accessories, spare parts, or tools.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Accessories, spare parts, or tools. 10.600 Section... tools. (a) General. Accessories, spare parts, or tools that are delivered with a good and that form part of the good's standard accessories, spare parts, or tools will be treated as originating goods if...

  12. 19 CFR 10.537 - Accessories, spare parts, or tools.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Accessories, spare parts, or tools. 10.537 Section... Free Trade Agreement Rules of Origin § 10.537 Accessories, spare parts, or tools. Accessories, spare parts, or tools that are delivered with a good and that form part of the good's standard...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 21 CFR 878.4700 - Surgical microscope and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Surgical microscope and accessories. 878.4700 Section 878.4700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... microscope and accessories. (a) Identification. A surgical microscope and accessories is an AC-powered...

  19. 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...

  20. 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...

  1. 21 CFR 868.5860 - Pressure tubing and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 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...

  2. 21 CFR 868.5860 - Pressure tubing and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 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...

  3. 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...

  4. 21 CFR 868.5860 - Pressure tubing and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 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...

  5. 21 CFR 876.5540 - Blood access device and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood access device and accessories. 876.5540... (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5540 Blood access device and accessories. (a) Identification. A blood access device and accessories is a device intended...

  6. 21 CFR 872.6300 - Rubber dam and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Rubber dam and accessories. 872.6300 Section 872...) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6300 Rubber dam and accessories. (a) Identification. A rubber dam and accessories is a device composed of a thin sheet of latex with a hole in...

  7. 21 CFR 872.6300 - Rubber dam and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Rubber dam and accessories. 872.6300 Section 872...) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6300 Rubber dam and accessories. (a) Identification. A rubber dam and accessories is a device composed of a thin sheet of latex with a hole in...

  8. 21 CFR 872.6300 - Rubber dam and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rubber dam and accessories. 872.6300 Section 872...) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6300 Rubber dam and accessories. (a) Identification. A rubber dam and accessories is a device composed of a thin sheet of latex with a hole in...

  9. 21 CFR 872.6300 - Rubber dam and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Rubber dam and accessories. 872.6300 Section 872...) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6300 Rubber dam and accessories. (a) Identification. A rubber dam and accessories is a device composed of a thin sheet of latex with a hole in...

  10. 21 CFR 872.6300 - Rubber dam and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Rubber dam and accessories. 872.6300 Section 872...) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6300 Rubber dam and accessories. (a) Identification. A rubber dam and accessories is a device composed of a thin sheet of latex with a hole in...

  11. 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...

  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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 21 CFR 884.6120 - Assisted reproduction accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Assisted reproduction accessories. 884.6120... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Assisted Reproduction Devices § 884.6120 Assisted reproduction accessories. (a) Identification. Assisted reproduction accessories are a group...

  3. 21 CFR 884.6120 - Assisted reproduction accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Assisted reproduction accessories. 884.6120... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Assisted Reproduction Devices § 884.6120 Assisted reproduction accessories. (a) Identification. Assisted reproduction accessories are a group...

  4. 21 CFR 884.6120 - Assisted reproduction accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Assisted reproduction accessories. 884.6120... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Assisted Reproduction Devices § 884.6120 Assisted reproduction accessories. (a) Identification. Assisted reproduction accessories are a group...

  5. 21 CFR 884.6120 - Assisted reproduction accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Assisted reproduction accessories. 884.6120... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Assisted Reproduction Devices § 884.6120 Assisted reproduction accessories. (a) Identification. Assisted reproduction accessories are a group...

  6. 21 CFR 884.6120 - Assisted reproduction accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Assisted reproduction accessories. 884.6120... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Assisted Reproduction Devices § 884.6120 Assisted reproduction accessories. (a) Identification. Assisted reproduction accessories are a group...

  7. 21 CFR 876.5980 - Gastrointestinal tube and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Gastrointestinal tube and accessories. 876.5980... tube and accessories. (a) Identification. A gastrointestinal tube and accessories is a device that..., gastrointestinal string and tubes to locate internal bleeding, double lumen tube for intestinal decompression...

  8. 21 CFR 876.5980 - Gastrointestinal tube and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Gastrointestinal tube and accessories. 876.5980... tube and accessories. (a) Identification. A gastrointestinal tube and accessories is a device that..., gastrointestinal string and tubes to locate internal bleeding, double lumen tube for intestinal decompression...

  9. 21 CFR 876.5980 - Gastrointestinal tube and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Gastrointestinal tube and accessories. 876.5980... tube and accessories. (a) Identification. A gastrointestinal tube and accessories is a device that..., gastrointestinal string and tubes to locate internal bleeding, double lumen tube for intestinal decompression...

  10. 21 CFR 876.5980 - Gastrointestinal tube and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Gastrointestinal tube and accessories. 876.5980... tube and accessories. (a) Identification. A gastrointestinal tube and accessories is a device that..., gastrointestinal string and tubes to locate internal bleeding, double lumen tube for intestinal decompression...

  11. 21 CFR 876.5980 - Gastrointestinal tube and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Gastrointestinal tube and accessories. 876.5980... tube and accessories. (a) Identification. A gastrointestinal tube and accessories is a device that..., gastrointestinal string and tubes to locate internal bleeding, double lumen tube for intestinal decompression...

  12. Detection of accessory spleens with indium 111-labeled autologous platelets

    SciTech Connect

    Davis, H.H., II; Varki, A.; Heaton, W.A.; Siegel, B.A.

    1980-01-01

    In two patients with recurrent immune thrombocytopenia, accessory splenic tissue was demonstrated by radionuclide imaging following administration of indium 111-labeled autologous platelets. In one of these patients, no accessory splenic tissue was seen on images obtained with technetium 99m sulfur colloid. This new technique provides a simple means for demonstrating accessory spleens and simultaneously evaluating the life-span of autologous platelets.

  13. Differential Localization of the Streptococcal Accessory Sec Components and Implications for Substrate Export

    PubMed Central

    Yen, Yihfen T.; Cameron, Todd A.; Bensing, Barbara A.; Seepersaud, Ravin; Zambryski, Patricia C.

    2013-01-01

    The accessory Sec system of Streptococcus gordonii is comprised of SecY2, SecA2, and five proteins (Asp1 through -5) that are required for the export of a serine-rich glycoprotein, GspB. We have previously shown that a number of the Asps interact with GspB, SecA2, or each other. To further define the roles of these Asps in export, we examined their subcellular localization in S. gordonii and in Escherichia coli expressing the streptococcal accessory Sec system. In particular, we assessed how the locations of these accessory Sec proteins were altered by the presence of other components. Using fluorescence microscopy, we found in E. coli that SecA2 localized within multiple foci at the cell membrane, regardless of whether other accessory Sec proteins were expressed. Asp2 alone localized to the cell poles but formed a similar punctate pattern at the membrane when SecA2 was present. Asp1 and Asp3 localized diffusely in the cytosol when expressed alone or with SecA2. However, these proteins redistributed to the membrane in a punctate arrangement when all of the accessory Sec components were present. Cell fractionation studies with S. gordonii further corroborated these microscopy results. Collectively, these findings indicate that Asp1 to -3 are not integral membrane proteins that form structural parts of the translocation channel. Instead, SecA2 serves as a docking site for Asp2, which in turn attracts a complex of Asp1 and Asp3 to the membrane. These protein interactions may be important for the trafficking of GspB to the cell membrane and its subsequent translocation. PMID:23204472

  14. Accessory cells for β-cell transplantation.

    PubMed

    Staels, W; De Groef, S; Heremans, Y; Coppens, V; Van Gassen, N; Leuckx, G; Van de Casteele, M; Van Riet, I; Luttun, A; Heimberg, H; De Leu, N

    2016-02-01

    Despite recent advances, insulin therapy remains a treatment, not a cure, for diabetes mellitus with persistent risk of glycaemic alterations and life-threatening complications. Restoration of the endogenous β-cell mass through regeneration or transplantation offers an attractive alternative. Unfortunately, signals that drive β-cell regeneration remain enigmatic and β-cell replacement therapy still faces major hurdles that prevent its widespread application. Co-transplantation of accessory non-islet cells with islet cells has been shown to improve the outcome of experimental islet transplantation. This review will highlight current travails in β-cell therapy and focuses on the potential benefits of accessory cells for islet transplantation in diabetes.

  15. CD4 down-modulation during infection of human T cells with human immunodeficiency virus type 1 involves independent activities of vpu, env, and nef.

    PubMed Central

    Chen, B K; Gandhi, R T; Baltimore, D

    1996-01-01

    The human immunodeficiency virus type 1 (HIV-1) genes vpu, env, and nef have all been implicated in modulating the levels of cell surface CD4 on infected cells. To quantitatively assess the relative contribution of each gene product to the regulation of CD4 during HIV infection of Jurkat T cells and peripheral blood mononuclear cells, we have developed an infectious HIV reporter system which expresses different combinations of these genes. To distinguish infected cells in the early or late stages of infection from uninfected cells, these viruses were designed to express human placental alkaline phosphatase with the kinetics of either early or late viral genes. Flow cytometry to detect placental alkaline phosphatase and CD4 in infected cells showed that vpu, env, and nef are independently capable of down-modulation of CD4. As predicted by their respective expression patterns, nef down-modulated CD4 rapidly during the early phase of virus infection whereas vpu and env functioned late in the infection. In both Jurkat cells and peripheral blood mononuclear cells, a combination of the three genes was more efficient than any one or two genes, demonstrating that all three genes are required to achieve maximal CD4 down-modulation. In primary cells, down-modulation of CD4 was less efficient than in Jurkat cells and there was a stronger dependence on nef function for reducing cell surface CD4. HIV therefore has three genes that are able to independently down-modulate CD4; together, they can eliminate the bulk of cell surface CD4. PMID:8709227

  16. Viral diversity and diversification of major non-structural genes vif, vpr, vpu, tat exon 1 and rev exon 1 during primary HIV-1 subtype C infection.

    PubMed

    Rossenkhan, Raabya; Novitsky, Vladimir; Sebunya, Theresa K; Musonda, Rosemary; Gashe, Berhanu A; Essex, M

    2012-01-01

    To assess the level of intra-patient diversity and evolution of HIV-1C non-structural genes in primary infection, viral quasispecies obtained by single genome amplification (SGA) at multiple sampling timepoints up to 500 days post-seroconversion (p/s) were analyzed. The mean intra-patient diversity was 0.11% (95% CI; 0.02 to 0.20) for vif, 0.23% (95% CI; 0.08 to 0.38) for vpr, 0.35% (95% CI; -0.05 to 0.75) for vpu, 0.18% (95% CI; 0.01 to 0.35) for tat exon 1 and 0.30% (95% CI; 0.02 to 0.58) for rev exon 1 during the time period 0 to 90 days p/s. The intra-patient diversity increased gradually in all non-structural genes over the first year of HIV-1 infection, which was evident from the vif mean intra-patient diversity of 0.46% (95% CI; 0.28 to 0.64), vpr 0.44% (95% CI; 0.24 to 0.64), vpu 0.84% (95% CI; 0.55 to 1.13), tat exon 1 0.35% (95% CI; 0.14 to 0.56 ) and rev exon 1 0.42% (95% CI; 0.18 to 0.66) during the time period of 181 to 500 days p/s. There was a statistically significant increase in viral diversity for vif (p = 0.013) and vpu (p = 0.002). No associations between levels of viral diversity within the non-structural genes and HIV-1 RNA load during primary infection were found. The study details the dynamics of the non-structural viral genes during the early stages of HIV-1C infection.

  17. Dermal fibroblasts contribute to multiple tissues in the accessory limb model.

    PubMed

    Hirata, Ayako; Gardiner, David M; Satoh, Akira

    2010-05-01

    The accessory limb model has become an alternative model for performing investigations of limb regeneration in an amputated limb. In the accessory limb model, a complete patterned limb can be induced as a result of an interaction between the wound epithelium, a nerve and dermal fibroblasts in the skin. Studies should therefore focus on examining these tissues. To date, however, a study of cellular contributions in the accessory limb model has not been reported. By using green fluorescent protein (GFP) transgenic axolotl tissues, we can trace cell fate at the tissue level. Therefore, in the present study, we transgrafted GFP skin onto the limb of a non-GFP host and induced an accessory limb to investigate cellular contributions. Previous studies of cell contribution to amputation-induced blastemas have demonstrated that dermal cells are the progenitors of many of the early blastema cells, and that these cells contribute to regeneration of the connective tissues, including cartilage. In the present study, we have determined that this same population of progenitor cells responds to signaling from the nerve and wound epithelium in the absence of limb amputation to form an ectopic blastema and regenerate the connective tissues of an ectopic limb. Blastema cells from dermal fibroblasts, however, did not differentiate into either muscle or neural cells, and we conclude that dermal fibroblasts are dedifferentiated along its developmental lineage.

  18. Accessory slips of the extensor digiti minimi.

    PubMed

    Li, Jing; Mao, Qing Hua

    2014-01-01

    During the educational dissection of a 69-year-old Chinese male cadaver, an extensor digiti minimi (EDM) with five slips on the right hand was discovered. Except for the two slips of the little finger, the two radial slips were inserted into the dorsal aponeurosis of the middle finger and the ring finger, respectively. The middle slip was connected to the junctura tendinum in the fourth intermetacarpal spaces. Variations in this region are of paramount importance for the reconstructive surgeons, who may utilize the accessory slips to restore functional capacity of the fingers.

  19. Optimization of diffuse reflectance infrared spectroscopy accessories

    SciTech Connect

    Hirschfeld, T.

    1986-11-01

    The value of diffuse reflectance as an infrared or near-infrared spectroscopic sampling procedure has been limited by the low efficiency of accessories designed for it. In terms of signal-to-noise ratio, these average 2-6% for integrating spheres and 10-12% for various ellipsoidal mirror arrangements. Much better performances, up to 37% efficiency, can be obtained by optimizing a concentric confocal ellipsoidal mirror arrangement by using a very large central opening in the amular collector mirror, and adapting the throughput of the detector to the geometry of the collected beam.

  20. Reviewing prescription spending and accessory usage.

    PubMed

    Oxenham, Julie

    This article aims to explore the role of the stoma nurse specialist in the community and how recent initiatives within the NHS have impacted on the roles in stoma care to react to the rising prescription costs in the specialty. The article will explore how the stoma care nurse conducted her prescription reviews within her own clinical commissioning group (CCG). The findings of the reviews will be highlighted by a small case history and a mini audit that reveals that some stoma patients may be using their stoma care accessories inappropriately, which may contribute to the rise in stoma prescription spending. To prevent the incorrect use of stoma appliances it may necessitate an annual review of ostomates (individuals who have a stoma), as the author's reviews revealed that inappropriate usage was particularly commonplace when a patient may have not been reviewed by a stoma care specialist for some considerable amount of time. Initial education of the ostomate and ongoing education of how stoma products work is essential to prevent the misuse of stoma appliances, particularly accessories, as the reviews revealed that often patients were not always aware of how their products worked in practice.

  1. 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.

  2. 21 CFR 876.5820 - Hemodialysis system and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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 and accessories to the blood compartment of the dialyzer, then returns through further tubing of...

  3. 21 CFR 876.5820 - Hemodialysis system and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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 and accessories to the blood compartment of the dialyzer, then returns through further tubing of...

  4. 21 CFR 876.5820 - Hemodialysis system and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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 and accessories to the blood compartment of the dialyzer, then returns through further tubing of...

  5. 21 CFR 876.5820 - Hemodialysis system and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 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 and accessories to the blood compartment of the dialyzer, then returns through further tubing of...

  6. 14 CFR 23.1192 - Engine accessory compartment diaphragm.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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... TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Equipment Miscellaneous Equipment § 23.1437 Accessories for multiengine airplanes. For multiengine...

  11. 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... TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Equipment Miscellaneous Equipment § 23.1437 Accessories for multiengine airplanes. For multiengine...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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 §...

  17. 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... Monitoring Devices § 884.2700 Intrauterine pressure monitor and accessories. (a) Identification. An intrauterine pressure monitor is a device designed to detect and measure intrauterine and amniotic...

  18. 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...

  19. 21 CFR 884.2660 - Fetal ultrasonic 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 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...

  20. 49 CFR 192.147 - Flanges and flange accessories.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ....147 Flanges and flange accessories. (a) Each flange or flange accessory (other than cast iron) must... be subjected in service. (c) Each flange on a flanged joint in cast iron pipe must conform in dimensions, drilling, face and gasket design to ASME/ANSI B16.1 and be cast integrally with the pipe,...

  1. 46 CFR 98.25-40 - Valves, fittings, and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Anhydrous Ammonia in Bulk § 98.25-40 Valves, fittings, and accessories. (a) All valves, flanges, fittings and accessory equipment shall be of a type suitable for use with anhydrous ammonia and shall be made... Engineering) of this chapter. Valves shall be fitted with noncorrosive material suitable for ammonia...

  2. 46 CFR 98.25-40 - Valves, fittings, and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Anhydrous Ammonia in Bulk § 98.25-40 Valves, fittings, and accessories. (a) All valves, flanges, fittings and accessory equipment shall be of a type suitable for use with anhydrous ammonia and shall be made... Engineering) of this chapter. Valves shall be fitted with noncorrosive material suitable for ammonia...

  3. 46 CFR 98.25-40 - Valves, fittings, and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Anhydrous Ammonia in Bulk § 98.25-40 Valves, fittings, and accessories. (a) All valves, flanges, fittings and accessory equipment shall be of a type suitable for use with anhydrous ammonia and shall be made... Engineering) of this chapter. Valves shall be fitted with noncorrosive material suitable for ammonia...

  4. 46 CFR 98.25-40 - Valves, fittings, and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Anhydrous Ammonia in Bulk § 98.25-40 Valves, fittings, and accessories. (a) All valves, flanges, fittings and accessory equipment shall be of a type suitable for use with anhydrous ammonia and shall be made... Engineering) of this chapter. Valves shall be fitted with noncorrosive material suitable for ammonia...

  5. 46 CFR 98.25-40 - Valves, fittings, and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Anhydrous Ammonia in Bulk § 98.25-40 Valves, fittings, and accessories. (a) All valves, flanges, fittings and accessory equipment shall be of a type suitable for use with anhydrous ammonia and shall be made... Engineering) of this chapter. Valves shall be fitted with noncorrosive material suitable for ammonia...

  6. Hunting for eruption ages in accessory minerals

    NASA Astrophysics Data System (ADS)

    Vazquez, J. A.

    2012-12-01

    A primary goal in geochronology is to provide precise and accurate ages for tephras that serve as chronostratigraphic markers for constraining the timing and rates of volcanism, sedimentation, climate change, and catastrophic events in Earth history. Zircon remains the most versatile accessory mineral for dating silicic tephras due to its common preservation in distal pyroclastic deposits, as well as the robustness of its U-Pb and U-series systems even after host materials have been hydrothermally altered or weathered. Countless studies document that zircon may be complexly zoned in age due to inheritance, contamination, recycling of antecrysts, protracted crystallization in long-lived magma reservoirs, or any combination of these. Other accessory minerals such as allanite or chevkinite can retain similar records of protracted crystallization. If the goal is to date the durations of magmatic crystallization, differentiation, and/or magma residence, then these protracted chronologies within and between accessory minerals are a blessing. However, if the goal is to date the timing of eruption with high precision, i.e., absolute ages with millennial-scale uncertainties, then this age zoning is a curse. Observations from ion microprobe 238U-230Th dating of Pleistocene zircon and allanite provide insight into the record of near-eruption crystallization in accessory minerals and serve as a guide for high-precision whole-crystal dating. Although imprecise relative to conventional techniques, ion probe analysis allows high-spatial resolution 238U-230Th dating that can document multi-millennial age distributions at the crystal scale. Analysis of unpolished rims and continuous depth profiling of zircon from small and large volume eruptions (e.g., Coso, Mono Craters, Yellowstone) reveals that the final several micrometers of crystallization often yield ages that are indistinguishable from associated eruption ages from the 40Ar/39Ar or (U-Th)/He methods. Using this approach, we

  7. Intrapancreatic accessory spleen diagnosed on radionuclide imaging.

    PubMed

    Belkhir, Sara Melboucy; Archambaud, Frédérique; Prigent, Alain; Chaumet-Riffaud, Philippe

    2009-09-01

    Intrapancreatic accessory spleen (IPAS) is ectopic splenic tissue distinct from the main spleen. A 46-year-old man with chronic hepatitis C, presented in 2006 with low right chest pain which led to a diagnosis of tuberculosis pleurisy. CT scan and MRI showed a round, homogenous, well limited mass of 3cm in the pancreas tail. Tc-99m heat-damaged red blood cell scintigraphy with SPECT-CT was performed to confirm the diagnosis of IPAS. Most cases of IPAS described in the literature were diagnosed by pathologists after distal pancreatectomy and splenectomy performed for a suspicion of pancreatic tumor. However, heat-damaged red blood cell scintigraphy remains the most commonly used diagnostic procedure for IPAS, even if superparamagnetic iron oxide MRI contrast agent may be used in the future.

  8. Fluid assisted installation of electrical cable accessories

    DOEpatents

    Mayer, Robert W.; Silva, Frank A.

    1977-01-01

    An electrical cable accessory includes a generally tubular member of elastomeric material which is to be installed by placement over a cylindrical surface to grip the cylindrical surface, when in appropriate assembled relation therewith, with a predetermined gripping force established by dilation of the tubular member, the installation being facilitated by introducing fluid under pressure, through means provided in the tubular member, between the tubular member and the cylindrical surface, and simultaneously impeding the escape of the fluid under pressure from between the tubular member and the cylindrical surface by means adjacent one of the ends of the tubular member to cause dilation of the tubular member and establish a fluid layer between the tubular member and the cylindrical surface, thereby reducing the gripping force during installation.

  9. Morphology of accessory genital glands of spotted paca (Agouti paca Linnaeus, 1766).

    PubMed

    Borges, Edson Moreira; Branco, Érika; de Lima, Ana Rita; Leal, Leonardo Martins; Martins, Leandro Luiz; Reis, Ana Carolina Gonçalves; Cruz, Claudinei; Machado, Márcia Rita Fernandes; Miglino, Maria Angelica

    2014-02-01

    The spotted paca is the second largest rodent in Brazil, where it is of great economic interest in impoverished regions in view of its prominence as a low-cost source of protein. Little is known about the morphology of the accessory genital glands of this species. Thus, we studied the position and morphology of the genitals in ten adult male spotted pacas. The animals were divided into two groups, five animals were used for fixing of samples in 10% aqueous formaldehyde for macroscopic studies and the other five animals were designated for microscopic analysis. These were arranged in pairs and had the vesicular, prostate, coagulating and bulbourethral glands identified, being structured as mucous glands, which lead into the pelvic urethra. It was concluded that the accessory genital glands found in the paca are the same as those found in most rodents, showing similar histological aspects.

  10. The scolopidial accessory organ in the Jerusalem cricket (Orthoptera: Stenopelmatidae).

    PubMed

    Strauß, Johannes

    2017-03-01

    Multiple mechanosensory organs form the subgenual organ complex in orthopteroid insects, located in the proximal tibia. In several Ensifera (Orthoptera), a small chordotonal organ, the so-called accessory organ, is the most posterior part of this sensory complex. In order to document the presence of this accessory organ among the Ensifera, the chordotonal sensilla and their innervation in the posterior tibia of two species of Jerusalem crickets (Stenopelmatidae: Stenopelmatus) is described. The sensory structures were stained by axonal tracing. Scolopidial sensilla occur in the posterior subgenual organ and the accessory organ in all leg pairs. The accessory organ contains 10-17 scolopidial sensilla. Both groups of sensilla are commonly spatially separated. However, in few cases neuronal fibres occurred between both organs. The two sensillum groups are considered as separate organs by the general spatial separation and innervation by different nerve branches. A functional role for mechanoreception is considered: since the accessory organ is located closely under the cuticle, sensilla may be suited to detect vibrations transferred over the leg's surface. This study extends the known taxa with an accessory organ, which occurs in several taxa of Ensifera. Comparative neuroanatomy thus suggests that the accessory organ may be conserved at least in Tettigoniidea.

  11. Successful treatment of accessory breast cancer with endocrine therapy#

    PubMed Central

    Wang, Chun-Xi; Guo, Shu-Li; Han, Li-Na

    2017-01-01

    Accessory breast cancers in males are extremely rare, and only a few cases have been reported in the literature. In this paper, an 87-year-old male patient was diagnosed with an accessory breast cancer by means of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), and immunohistochemistry based on needle biopsy, and has undergone successful resection and postoperative adjuvant endocrine therapy. He was the oldest male patient with an accessory breast cancer reported in the Chinese Hospital Knowledge Database and PubMed literature from 1975 to 2015. PMID:28070998

  12. Acetylation of the c-MYC oncoprotein is required for cooperation with the HTLV-1 p30{sup II} accessory protein and the induction of oncogenic cellular transformation by p30{sup II}/c-MYC

    SciTech Connect

    Romeo, Megan M.; Ko, Bookyung; Kim, Janice; Brady, Rebecca; Heatley, Hayley C.; He, Jeffrey; Harrod, Carolyn K.; Barnett, Braden; Ratner, Lee; Lairmore, Michael D.; Martinez, Ernest; Lüscher, Bernhard; Robson, Craig N.; Henriksson, Marie; Harrod, Robert

    2015-02-15

    The human T-cell leukemia retrovirus type-1 (HTLV-1) p30{sup II} protein is a multifunctional latency-maintenance factor that negatively regulates viral gene expression and deregulates host signaling pathways involved in aberrant T-cell growth and proliferation. We have previously demonstrated that p30{sup II} interacts with the c-MYC oncoprotein and enhances c-MYC-dependent transcriptional and oncogenic functions. However, the molecular and biochemical events that mediate the cooperation between p30{sup II} and c-MYC remain to be completely understood. Herein we demonstrate that p30{sup II} induces lysine-acetylation of the c-MYC oncoprotein. Acetylation-defective c-MYC Lys→Arg substitution mutants are impaired for oncogenic transformation with p30{sup II} in c-myc{sup −/−} HO15.19 fibroblasts. Using dual-chromatin-immunoprecipitations (dual-ChIPs), we further demonstrate that p30{sup II} is present in c-MYC-containing nucleoprotein complexes in HTLV-1-transformed HuT-102 T-lymphocytes. Moreover, p30{sup II} inhibits apoptosis in proliferating cells expressing c-MYC under conditions of genotoxic stress. These findings suggest that c-MYC-acetylation is required for the cooperation between p30{sup II}/c-MYC which could promote proviral replication and contribute to HTLV-1-induced carcinogenesis. - Highlights: • Acetylation of c-MYC is required for oncogenic transformation by HTLV-1 p30{sup II}/c-MYC. • Acetylation-defective c-MYC mutants are impaired for foci-formation by p30{sup II}/c-MYC. • The HTLV-1 p30{sup II} protein induces lysine-acetylation of c-MYC. • p30{sup II} is present in c-MYC nucleoprotein complexes in HTLV-1-transformed T-cells. • HTLV-1 p30{sup II} inhibits apoptosis in c-MYC-expressing proliferating cells.

  13. AcCNET (Accessory Genome Constellation Network): comparative genomics software for accessory genome analysis using bipartite networks.

    PubMed

    Lanza, Val F; Baquero, Fernando; de la Cruz, Fernando; Coque, Teresa M

    2017-01-15

    AcCNET (Accessory genome Constellation Network) is a Perl application that aims to compare accessory genomes of a large number of genomic units, both at qualitative and quantitative levels. Using the proteomes extracted from the analysed genomes, AcCNET creates a bipartite network compatible with standard network analysis platforms. AcCNET allows merging phylogenetic and functional information about the concerned genomes, thus improving the capability of current methods of network analysis. The AcCNET bipartite network opens a new perspective to explore the pangenome of bacterial species, focusing on the accessory genome behind the idiosyncrasy of a particular strain and/or population.

  14. Acetylation of the c-MYC oncoprotein is required for cooperation with the HTLV-1 p30(II) accessory protein and the induction of oncogenic cellular transformation by p30(II)/c-MYC.

    PubMed

    Romeo, Megan M; Ko, Bookyung; Kim, Janice; Brady, Rebecca; Heatley, Hayley C; He, Jeffrey; Harrod, Carolyn K; Barnett, Braden; Ratner, Lee; Lairmore, Michael D; Martinez, Ernest; Lüscher, Bernhard; Robson, Craig N; Henriksson, Marie; Harrod, Robert

    2015-02-01

    The human T-cell leukemia retrovirus type-1 (HTLV-1) p30(II) protein is a multifunctional latency-maintenance factor that negatively regulates viral gene expression and deregulates host signaling pathways involved in aberrant T-cell growth and proliferation. We have previously demonstrated that p30(II) interacts with the c-MYC oncoprotein and enhances c-MYC-dependent transcriptional and oncogenic functions. However, the molecular and biochemical events that mediate the cooperation between p30(II) and c-MYC remain to be completely understood. Herein we demonstrate that p30(II) induces lysine-acetylation of the c-MYC oncoprotein. Acetylation-defective c-MYC Lys→Arg substitution mutants are impaired for oncogenic transformation with p30(II) in c-myc(-/-) HO15.19 fibroblasts. Using dual-chromatin-immunoprecipitations (dual-ChIPs), we further demonstrate that p30(II) is present in c-MYC-containing nucleoprotein complexes in HTLV-1-transformed HuT-102 T-lymphocytes. Moreover, p30(II) inhibits apoptosis in proliferating cells expressing c-MYC under conditions of genotoxic stress. These findings suggest that c-MYC-acetylation is required for the cooperation between p30(II)/c-MYC which could promote proviral replication and contribute to HTLV-1-induced carcinogenesis.

  15. 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...

  16. 21 CFR 876.5090 - Suprapubic urological catheter and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 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...

  17. 21 CFR 884.2740 - Perinatal monitoring system and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... heart rate by means of combining and coordinating uterine contraction and fetal heart monitors with... SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Monitoring Devices § 884.2740 Perinatal monitoring system and accessories. (a) Identification. A...

  18. 21 CFR 884.2740 - Perinatal monitoring system and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... heart rate by means of combining and coordinating uterine contraction and fetal heart monitors with... SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Monitoring Devices § 884.2740 Perinatal monitoring system and accessories. (a) Identification. A...

  19. 21 CFR 872.3980 - Endosseous dental implant accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... abutments, aid in the fabrication of dental prosthetics, and be used as an accessory with endosseous dental..., countertorque devices, placement and removal tools, laboratory pieces used for fabrication of dental...

  20. 21 CFR 872.3980 - Endosseous dental implant accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... abutments, aid in the fabrication of dental prosthetics, and be used as an accessory with endosseous dental..., countertorque devices, placement and removal tools, laboratory pieces used for fabrication of dental...

  1. 21 CFR 872.3980 - Endosseous dental implant accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... abutments, aid in the fabrication of dental prosthetics, and be used as an accessory with endosseous dental..., countertorque devices, placement and removal tools, laboratory pieces used for fabrication of dental...

  2. 21 CFR 872.3980 - Endosseous dental implant accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... abutments, aid in the fabrication of dental prosthetics, and be used as an accessory with endosseous dental..., countertorque devices, placement and removal tools, laboratory pieces used for fabrication of dental...

  3. 21 CFR 876.5630 - Peritoneal dialysis system and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... accessories is a device that is used as an artificial kidney system for the treatment of patients with renal failure or toxemic conditions, and that consists of a peritoneal access device, an administration set...

  4. 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... excessive restorative materials, such as gold, and to smooth rough surfaces from oral restorations, such...

  5. 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.

  6. 21 CFR 872.4200 - Dental handpiece and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) Identification. A dental handpiece and accessories is an AC-powered, water-powered, air-powered, or belt-driven... restorations, such as fillings, and for cleaning teeth. (b) Classification. Class I....

  7. 21 CFR 872.4200 - Dental handpiece and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) Identification. A dental handpiece and accessories is an AC-powered, water-powered, air-powered, or belt-driven... restorations, such as fillings, and for cleaning teeth. (b) Classification. Class I....

  8. 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... excessive restorative materials, such as gold, and to smooth rough surfaces from oral restorations, such...

  9. PERSISTENT PUPILLARY MEMBRANE OR ACCESSORY IRIS MEMBRANE?.

    PubMed

    Gavriş, Monica; Horge, Ioan; Avram, Elena; Belicioiu, Roxana; Olteanu, Ioana Alexandra; Kedves, Hanga

    2015-01-01

    Frequently, in literature and curent practice, accessory iris membrane (AIM) and persistant pupillary membrane (PPM) are confused. Both AIM and PPM are congenital iris anomalies in which fine or thick iris strands arrise form the collarette and obscure the pupil. AIM, which is also called iris duplication, closely resembles the normal iris tissue in color and thickness and presents a virtual second pseudopupil aperture in the centre while PPM even in its extreme forms presents as a translucent or opaque membranous structure that extends across the pupil and has no pseudopupil. Mydriatiscs, laser treatment or surgery is used to clear the visual axis and optimize visual development. Surgical intervention is reserved for large, dense AIMs and PPMs. Our patient, a 29 year old male, has come with bilateral dense AIM, bilateral compound hyperopic astigmatism, BCVA OD = 0.6, BCVA OS = 0.4, IOP OU = 17 mmHg. To improve the visual acuity of the patient we decided to do a bilateral membranectomy, restoring in this way transparency of the visual axis. After surgery, the visual acuity improved to BCVA OD= 0.8, BCVA OS=0.8.

  10. 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

  11. Accessory subunits are integral for assembly and function of human mitochondrial complex I.

    PubMed

    Stroud, David A; Surgenor, Elliot E; Formosa, Luke E; Reljic, Boris; Frazier, Ann E; Dibley, Marris G; Osellame, Laura D; Stait, Tegan; Beilharz, Traude H; Thorburn, David R; Salim, Agus; Ryan, Michael T

    2016-10-06

    Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the mitochondrial respiratory chain and is composed of 45 subunits in humans, making it one of the largest known multi-subunit membrane protein complexes. Complex I exists in supercomplex forms with respiratory chain complexes III and IV, which are together required for the generation of a transmembrane proton gradient used for the synthesis of ATP. Complex I is also a major source of damaging reactive oxygen species and its dysfunction is associated with mitochondrial disease, Parkinson's disease and ageing. Bacterial and human complex I share 14 core subunits that are essential for enzymatic function; however, the role and necessity of the remaining 31 human accessory subunits is unclear. The incorporation of accessory subunits into the complex increases the cellular energetic cost and has necessitated the involvement of numerous assembly factors for complex I biogenesis. Here we use gene editing to generate human knockout cell lines for each accessory subunit. We show that 25 subunits are strictly required for assembly of a functional complex and 1 subunit is essential for cell viability. Quantitative proteomic analysis of cell lines revealed that loss of each subunit affects the stability of other subunits residing in the same structural module. Analysis of proteomic changes after the loss of specific modules revealed that ATP5SL and DMAC1 are required for assembly of the distal portion of the complex I membrane arm. Our results demonstrate the broad importance of accessory subunits in the structure and function of human complex I. Coupling gene-editing technology with proteomics represents a powerful tool for dissecting large multi-subunit complexes and enables the study of complex dysfunction at a cellular level.

  12. 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

  13. Accessory Soleus: A Case Report of Exertional Compartment and Tarsal Tunnel Syndrome Associated With an Accessory Soleus Muscle.

    PubMed

    Carrington, Scott C; Stone, Paul; Kruse, Dustin

    2016-01-01

    An accessory soleus muscle is a rare anatomic variant that frequently presents as an asymptomatic soft tissue swelling in the posteromedial ankle. Less frequently, the anomalous muscle can cause pain and swelling with activity. We present the case of a 17-year-old male with exertional compartment syndrome and associated tarsal tunnel syndrome secondary to a very large accessory soleus muscle. After surgical excision, the patient was able to return to full activity with complete resolution of symptoms.

  14. Chapter Eleven: The Drosophila Accessory Gland as a Model for Prostate Cancer and Other Pathologies

    PubMed Central

    Wilson, C.; Leiblich, A.; Goberdhan, D.C.I.; Hamdy, F.

    2017-01-01

    The human prostate is a gland of the male reproductive tract, which together with the seminal vesicles, is responsible for most seminal fluid production. It is a common site of cancer, and unlike other glands, it typically enlarges in aging men. In flies, the male accessory glands make many major seminal fluid components. Like their human equivalents, they secrete proteins from several conserved families, including proteases, lectins, and cysteine-rich secretory proteins, some of which interact with sperm and affect fertility. A key protein, sex peptide, is not conserved in vertebrates but plays a central role in mediating long-term effects on females after mating. Although postmitotic, one epithelial cell type in the accessory glands, the secondary cell, continues to grow in adults. It secretes microvesicles called exosomes from the endosomal multivesicular body, which, after mating, fuse with sperm. They also appear to affect female postmating behavior. Remarkably, the human prostate epithelium also secretes exosomes, which fuse to sperm in vitro to modulate their activity. Exosomes from prostate and other cancer cells are increasingly proposed to play fundamental roles in modulating the tumor microenvironment and in metastasis. Here we review a diverse accessory gland literature, which highlights functional analogies between the male reproductive glands of flies and humans, and a critical role for extracellular vesicles in allowing seminal fluid to promote male interests within the female. We postulate that secondary cells and prostate epithelial cells use common mechanisms to control growth, secretion, and signaling, which are relevant to prostate and other cancers, and can be genetically dissected in the uniquely tractable fly model. PMID:28057306

  15. The human immunodeficiency virus (HIV) Rev-binding protein (HRB) is a co-factor for HIV-1 Nef-mediated CD4 downregulation.

    PubMed

    Landi, Alessia; Timermans, Cristina Garcia; Naessens, Evelien; Vanderstraeten, Hanne; Stove, Veronique; Verhasselt, Bruno

    2016-03-01

    Human immunodeficiency virus type 1 (HIV-1)-mediated CD4 downregulation is an important determinant of viral replication in vivo. Research on cellular co-factors involved in this process could lead to the identification of potential therapeutic targets. We found that CD4 surface levels were significantly higher in HIV-1-infected cells knocked-down for the HIV Rev-binding protein (HRB) compared with control cells. HRB knock-down affected CD4 downregulation induced by Nef but not by HIV-1 Vpu. Interestingly, the knock-down of the related protein HRBL (HRB-like), but not of the HRB interaction partner EPS15 (epidermal growth factor receptor pathway substrate 15), increased CD4 levels in Vpu-expressing cells significantly. Both of these proteins are known to be involved in HIV-1-mediated CD4 downregulation as co-factors of HIV-1 Nef. These results identify HRB as a previously unknown co-factor for HIV-1 Nef-mediated CD4 downregulation and highlight differences with the related protein HRBL, which affects the CD4 downregulation in a dual role as co-factor of both HIV-1 Nef and Vpu.

  16. 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.

  17. Zonal organization of the mammalian main and accessory olfactory systems.

    PubMed Central

    Mori, K; von Campenhause, H; Yoshihara, Y

    2000-01-01

    Zonal organization is one of the characteristic features observed in both main and accessory olfactory systems. In the main olfactory system, most of the odorant receptors are classified into four groups according to their zonal expression patterns in the olfactory epithelium. Each group of odorant receptors is expressed by sensory neurons distributed within one of four circumscribed zones. Olfactory sensory neurons in a given zone of the epithelium project their axons to the glomeruli in a corresponding zone of the main olfactory bulb. Glomeruli in the same zone tend to represent similar odorant receptors having similar tuning specificity to odorants. Vomeronasal receptors (or pheromone receptors) are classified into two groups in the accessory olfactory system. Each group of receptors is expressed by vomeronasal sensory neurons in either the apical or basal zone of the vomeronasal epithelium. Sensory neurons in the apical zone project their axons to the rostral zone of the accessory olfactory bulb and form synaptic connections with mitral tufted cells belonging to the rostral zone. Signals originated from basal zone sensory neurons are sent to mitral tufted cells in the caudal zone of the accessory olfactory bulb. We discuss functional implications of the zonal organization in both main and accessory olfactory systems. PMID:11205342

  18. Binding-induced Stabilization and Assembly of the Phage P22 Tail Accessory Factor gp4

    SciTech Connect

    Olia,A.; Al-Bassam, J.; Winn-Stapley, D.; Joss, L.; Casjens, S.; Cingolani, G.

    2006-01-01

    To infect and replicate, bacteriophage P22 injects its 43 kbp genome across the cell wall of Salmonella enterica serovar Typhimurium. The attachment of phage P22 to the host cell as well as the injection of the viral DNA into the host is mediated by the virion's tail complex. This 2.8 MDa molecular machine is formed by five proteins, which include the portal protein gp1, the adhesion tailspike protein gp9, and three tail accessory factors: gp4, gp10, gp26. We have isolated the tail accessory factor gp4 and characterized its structure and binding interactions with portal protein. Interestingly, gp4 exists in solution as a monomer, which displays an exceedingly low structural stability (T{sub m} 34 {sup o}C). Unfolded gp4 is prone to aggregation within a narrow range of temperatures both in vitro and in Salmonella extracts. In the virion the thermal unfolding of gp4 is prevented by the interaction with the dodecameric portal protein, which stabilizes the structure of gp4 and suppresses unfolded gp4 from irreversibly aggregating in the Salmonella milieu. The structural stabilization of gp4 is accompanied by the concomitant oligomerization of the protein to form a ring of 12 subunits bound to the lower end of the portal ring. The interaction of gp4 with portal protein is complex and likely involves the distinct binding of two non-equivalent sets of six gp4 proteins. Binding of the first set of six gp4 equivalents to dodecameric portal protein yields a gp(1){sub 12}:gp(4){sub 6} assembly intermediate, which is stably populated at 30 {sup o}C and can be resolved by native gel electrophoresis. The final product of the assembly reaction is a bi-dodecameric gp(1){sub 12}:gp(4){sub 12} complex, which appears hollow by electron microscopy, suggesting that gp4 does not physically plug the DNA entry/exit channel, but acts as a structural adaptor for the other tail accessory factors: gp10 and gp26.

  19. Case report: accessory head of the deep forearm flexors

    PubMed Central

    JONES, M.; ABRAHAMS, P. H.; SAÑUDO, J. R.

    1997-01-01

    In 1813 Gantzer described 2 accessory muscles in the human forearm which bear his name (Wood, 1868; Macalister, 1875) and these have subsequently been reported with variable attachments (Wood, 1868; Macalister, 1875; Turner, 1879; Schäfer & Thane, 1894; Le Double, 1897; Dykes & Anson, 1944; Mangini, 1960; Malhotra et al. 1982; Kida, 1988; Tountas & Bergman, 1993). The accessory heads of the deep flexors of the forearm (Gantzer's muscles) have been described as 2 different small bellies which insert either into FPL or FDP. There are no previous reports which have mentioned the existence of an accessory muscle which inserts into both of the 2 deep flexors of the forearm as in the case presented here. PMID:9306208

  20. Accessory Pancreatic Duct Patterns and Their Clinical Implications

    PubMed Central

    Prasanna, Lokadolalu Chandracharya; Rajagopal, KV; Thomas, Huban R

    2015-01-01

    Context and Objective: Accessory pancreatic duct (APD) designed to reduce the pressure of major pancreatic duct by forming a secondary drainage channel. Few studies have mentioned the variant types of accessory ducts and their mode of formation, some of these have a clear clinical significance. Present study is aimed to evaluate the possible variations in the APD and its terminations. Materials and Methods: Forty formalin fixed adult human pancreas with duodenum in situ specimens were studied by injecting 1% aqueous eosin, followed by piece meal dissection of the head of the pancreas from posterior surface. Formation, tributaries, relations, and the termination of the accessory pancreatic duct were noted and photographed. Results: Accessory ducts revealed 50% belonged to long type, 22.5% were of short and ansa pancreatica type each, and embryonic type of duct pattern was seen in 5% specimens. 75% of long type ducts showed positive patency with eosin dye, followed by ansa type (44.4%), and least patency was found in short type (22.2%). With regard to the patency of the accessory pancreatic ducts towards their termination, we found 52.5% of the accessory ducts and 5% of the embryonic type pancreatic ducts were patent and in 42.5% of the specimen the ducts were obliterated. In 85% of specimens the minor duodenal papillae was anterosuperior to the major papilla and superior to the major papillae in 10% of the cases, and in 5% minor papillae was absent. The average distance between the two papillae was 2.35 cm. Conclusion: The knowledge of the complex anatomical relations of the gland with its duct, duodenum and bile ducts are essential for the surgeons and sinologists to plan and perform both the diagnostic as well as therapeutic procedures effectively. PMID:25954609

  1. 76 FR 24522 - In the Matter of Certain Handbags, Luggage, Accessories, and Packaging Thereof; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-02

    ... From the Federal Register Online via the Government Publishing Office INTERNATIONAL TRADE COMMISSION In the Matter of Certain Handbags, Luggage, Accessories, and Packaging Thereof; Notice of... handbags, luggage, accessories, and packaging thereof by reason of infringement of certain claims of...

  2. 21 CFR 884.6190 - Assisted reproductive microscopes and microscope accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Assisted Reproduction.... Assisted reproduction microscopes and microscope accessories (excluding microscope stage warmers, which are classified under assisted reproduction accessories) are optical instruments used to enlarge images of...

  3. 21 CFR 884.6190 - Assisted reproductive microscopes and microscope accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Assisted Reproduction.... Assisted reproduction microscopes and microscope accessories (excluding microscope stage warmers, which are classified under assisted reproduction accessories) are optical instruments used to enlarge images of...

  4. 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.... Assisted reproduction microscopes and microscope accessories (excluding microscope stage warmers, which are classified under assisted reproduction accessories) are optical instruments used to enlarge images of...

  5. 21 CFR 884.6190 - Assisted reproductive microscopes and microscope accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Assisted Reproduction.... Assisted reproduction microscopes and microscope accessories (excluding microscope stage warmers, which are classified under assisted reproduction accessories) are optical instruments used to enlarge images of...

  6. 21 CFR 884.6190 - Assisted reproductive microscopes and microscope accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Assisted Reproduction.... Assisted reproduction microscopes and microscope accessories (excluding microscope stage warmers, which are classified under assisted reproduction accessories) are optical instruments used to enlarge images of...

  7. Tex, a putative transcriptional accessory factor, is involved in pathogen fitness in Streptococcus pneumoniae.

    PubMed

    He, Xiangyun; Thornton, Justin; Carmicle-Davis, Stephanie; McDaniel, Larry S

    2006-12-01

    We have identified a pneumococcal gene, tex, which has the potential to regulate gene expression. The tex gene is named for its role in toxin expression in Bordetella pertussis, where it was characterized as an essential gene. Homologous sequences have been found in both Gram-positive and Gram-negative bacteria and are highly conserved at the protein level. Tex family proteins contain a S1 RNA-binding domain at the C-terminus. Members of this family are putative transcriptional accessory factors. Although tex in Streptococcus pneumoniae is homologous to that in B. pertussis, there are distinct differences. Since the tex gene in S. pneumoniae is not an essential gene, we were able to delete tex in strain D39. The tex knockout mutant, DeltaTex, did not affect production of the pneumococcal toxin pneumolysin. However, we observed decreased growth of DeltaTex in the presence of the wild-type strain both in vitro and in vivo as determined by generation numbers and competitive index (CI). The interaction between recombinant Tex and nucleic acids was confirmed by southwestern and northwestern analysis, supporting its role as a transcriptional accessory factor.

  8. Antidromic Atrioventricular Reciprocating Tachycardia Using a Concealed Retrograde Conducting Left Lateral Accessory Pathway.

    PubMed

    Gonzalez, Jaime E; Zipse, Matthew M; Nguyen, Duy T; Sauer, William H

    2016-03-01

    Atrioventricular reciprocating tachycardia is a common cause of undifferentiated supraventricular tachycardia. In patients with manifest or concealed accessory pathways, it is imperative to assess for the presence of other accessory pathways. Multiple accessory pathways are present in 4% to 10% of patients and are more common in patients with structural heart disease. In rare cases, multiple accessory pathways can act as the anterograde and retrograde limbs of the tachycardia.

  9. 19 CFR 10.920 - 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. 10.920 Section 10.920 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Peru...

  10. 19 CFR 10.920 - Accessories, spare parts, or tools.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Accessories, spare parts, or tools. 10.920 Section 10.920 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Peru...

  11. 19 CFR 10.920 - Accessories, spare parts, or tools.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Accessories, spare parts, or tools. 10.920 Section 10.920 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Peru...

  12. 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...

  13. 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...

  14. 19 CFR 10.1020 - Accessories, spare parts, or tools.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Accessories, spare parts, or tools. 10.1020 Section 10.1020 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United...

  15. 19 CFR 10.1020 - Accessories, spare parts, or tools.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Accessories, spare parts, or tools. 10.1020 Section 10.1020 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United...

  16. 19 CFR 10.1020 - 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. 10.1020 Section 10.1020 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United...

  17. 21 CFR 876.5900 - Ostomy pouch and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... attached to the patient's skin by an adhesive material and that is intended for use as a receptacle for... generic type of device and its accessories includes the ostomy pouch, ostomy adhesive, the disposable... bag, ostomy drainage bag with adhesive, stomal bag, ostomy protector, and the ostomy size...

  18. Four accessory (supernumerary) intrathoracic ribs: a case report.

    PubMed

    Prados, Jose; Archilla, Francisco; Melguizo, Consolación; Aranega, Antonia

    2013-09-01

    Accessory (supernumerary) intrathoracic ribs are a very rare congenital disorder. Here, we present the first case of multiple supernumerary intrathoracic ribs in an adult, which are present consecutively between ribs 1 and 4 and without articulation with the vertebrae. Despite this, anatomical variation is usually silent and accidentally discovered; its knowledge can prevent confusion with other structures during imaging diagnostic techniques of thoracic pathologies.

  19. 21 CFR 876.5900 - Ostomy pouch and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... attached to the patient's skin by an adhesive material and that is intended for use as a receptacle for... generic type of device and its accessories includes the ostomy pouch, ostomy adhesive, the disposable... bag, ostomy drainage bag with adhesive, stomal bag, ostomy protector, and the ostomy size...

  20. 21 CFR 876.5900 - Ostomy pouch and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... attached to the patient's skin by an adhesive material and that is intended for use as a receptacle for... generic type of device and its accessories includes the ostomy pouch, ostomy adhesive, the disposable... bag, ostomy drainage bag with adhesive, stomal bag, ostomy protector, and the ostomy size...

  1. 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.

  2. 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…

  3. 21 CFR 884.4900 - Obstetric table and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 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....

  4. 21 CFR 884.4900 - Obstetric table and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 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....

  5. 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 §...

  6. 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 §...

  7. 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 §...

  8. 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...

  9. 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...

  10. A treatment accessory for CNS irradiation in children.

    PubMed

    Bukovitz, A G; Timo, J

    1975-09-01

    A treatment accessory for use in CNS radiotherapy of small children enables the head and spinal fields to be treated while the child lies supine. Children are not moved during therapy which minimizes the problem of gaps between the head and spinal fields.

  11. 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 §...

  12. 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 §...

  13. 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...

  14. 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...

  15. 21 CFR 874.4720 - Mediastinoscope and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Surgical Devices § 874.4720 Mediastinoscope and... device with any of a group of accessory devices which attach to the mediastinoscope and is intended to examine or treat tissue in the area separating the lungs. The device is inserted transthoracicly and...

  16. 21 CFR 874.4720 - Mediastinoscope and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Surgical Devices § 874.4720 Mediastinoscope and... device with any of a group of accessory devices which attach to the mediastinoscope and is intended to examine or treat tissue in the area separating the lungs. The device is inserted transthoracicly and...

  17. Schwannoma of the Spinal Accessory Nerve: A Case Report

    PubMed Central

    Kohli, Ritesh; Singh, Surinder; Gupta, Sahwani K.; Matreja, Prithpal S.

    2013-01-01

    We are reporting a rare case of a schwannoma which originated from the cervical portion of the spinal accessory nerve, which was located in the left posterior triangle of the neck and did not have any neurological deficit, which was diagnosed by the Magnetic Resonance Imaging (MRI) scan and confirmed histopathologically after surgery. PMID:24086895

  18. 21 CFR 876.1500 - Endoscope and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., and allow observation or manipulation of body cavities, hollow organs, and canals. The device consists of various rigid or flexible instruments that are inserted into body spaces and may include an optical system for conveying an image to the user's eye and their accessories may assist in gaining...

  19. 21 CFR 876.1500 - Endoscope and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., and allow observation or manipulation of body cavities, hollow organs, and canals. The device consists of various rigid or flexible instruments that are inserted into body spaces and may include an optical system for conveying an image to the user's eye and their accessories may assist in gaining...

  20. 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... phonocardiographic monitor is a device designed to detect, measure, and record fetal heart sounds electronically,...

  1. 21 CFR 884.2740 - Perinatal monitoring system and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Perinatal monitoring system and accessories. 884.2740 Section 884.2740 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... heart rate by means of combining and coordinating uterine contraction and fetal heart monitors...

  2. 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... phonocardiographic monitor is a device designed to detect, measure, and record fetal heart sounds electronically,...

  3. 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... phonocardiographic monitor is a device designed to detect, measure, and record fetal heart sounds electronically,...

  4. 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... phonocardiographic monitor is a device designed to detect, measure, and record fetal heart sounds electronically,...

  5. 21 CFR 884.2740 - Perinatal monitoring system and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Perinatal monitoring system and accessories. 884.2740 Section 884.2740 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... heart rate by means of combining and coordinating uterine contraction and fetal heart monitors...

  6. 21 CFR 884.2740 - Perinatal monitoring system and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Perinatal monitoring system and accessories. 884.2740 Section 884.2740 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... heart rate by means of combining and coordinating uterine contraction and fetal heart monitors...

  7. 21 CFR 876.1500 - Endoscope and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., and allow observation or manipulation of body cavities, hollow organs, and canals. The device consists of various rigid or flexible instruments that are inserted into body spaces and may include an optical system for conveying an image to the user's eye and their accessories may assist in gaining...

  8. 21 CFR 872.5410 - Orthodontic appliance and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Orthodontic appliance and accessories. 872.5410 Section 872.5410 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... orthodontic treatment. The device is affixed to a tooth so that pressure can be exerted on the teeth....

  9. 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 872.4200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... restorations, such as fillings, and for cleaning teeth. (b) Classification. Class I....

  10. 21 CFR 872.5410 - Orthodontic appliance and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Orthodontic appliance and accessories. 872.5410 Section 872.5410 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... orthodontic treatment. The device is affixed to a tooth so that pressure can be exerted on the teeth....

  11. 21 CFR 872.5410 - Orthodontic appliance and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Orthodontic appliance and accessories. 872.5410 Section 872.5410 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... orthodontic treatment. The device is affixed to a tooth so that pressure can be exerted on the teeth....

  12. 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 872.4200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... restorations, such as fillings, and for cleaning teeth. (b) Classification. Class I....

  13. 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 872.4200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... restorations, such as fillings, and for cleaning teeth. (b) Classification. Class I....

  14. 21 CFR 872.5410 - Orthodontic appliance and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Orthodontic appliance and accessories. 872.5410 Section 872.5410 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... orthodontic treatment. The device is affixed to a tooth so that pressure can be exerted on the teeth....

  15. 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 Section 872.6640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... intended to supply power to and serve as a base for other dental devices, such as a dental handpiece,...

  16. 21 CFR 870.4200 - Cardiopulmonary bypass accessory equipment.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass accessory equipment. 870.4200 Section 870.4200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., and (ii) The guidance document entitled “Guidance on the Performance Standard for Electrode Lead...

  17. 21 CFR 870.4200 - Cardiopulmonary bypass accessory equipment.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass accessory equipment. 870.4200 Section 870.4200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., and (ii) The guidance document entitled “Guidance on the Performance Standard for Electrode Lead...

  18. 21 CFR 876.5820 - Hemodialysis system and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Hemodialysis system and accessories. 876.5820 Section 876.5820 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... conditions and that consists of an extracorporeal blood system, a conventional dialyzer, a dialysate...

  19. Accessory child safety harnesses: do the risks outweigh the benefits?

    PubMed

    Brown, Julie; Wainohu, Derek; Aquilina, Peter; Suratno, Basuki; Kelly, Paul; Bilston, Lynne E

    2010-01-01

    Accessory child safety harnesses are available in some countries as alternative restraints for young children or as an accessory restraint used with booster seats. Their use, in Australia at least, is becoming more common. There have been concerns that the risk of misuse of these restraints outweighs any potential benefit this system might have over a retractable lap-shoulder belt system used with a booster seat. However to date there is no evidence to confirm or deny this. This study used laboratory simulated frontal crash tests to examine the performance of accessory child safety harness systems compared to the lap-shoulder belt when used alone and when used with two common designs of Australian booster seat. The performance of the child safety harness system when misused was also investigated. The results demonstrate that the correctly used child safety harness system performed no better than the lap-shoulder system, and in fact allows for a greater risk of submarining. Furthermore, one common form of child safety harness misuse, where the harness is over-tightened causing the lap belt to be positioned high over the abdomen, allowed extremely undesirable dummy motion. This involved gross submarining and direct contact between the harness system and the dummy's neck. These findings suggest that the risks associated with accessory child safety harness systems most likely outweigh any potential benefits, in frontal impacts at least.

  20. 21 CFR 874.4720 - Mediastinoscope and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Mediastinoscope and accessories. 874.4720 Section 874.4720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Surgical Devices § 874.4720 Mediastinoscope...

  1. 21 CFR 874.4720 - Mediastinoscope and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Mediastinoscope and accessories. 874.4720 Section 874.4720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Surgical Devices § 874.4720 Mediastinoscope...

  2. 21 CFR 874.4720 - Mediastinoscope and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Mediastinoscope and accessories. 874.4720 Section 874.4720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Surgical Devices § 874.4720 Mediastinoscope...

  3. 19 CFR 10.456 - Accessories, spare parts or tools.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Accessories, spare parts or tools. 10.456 Section 10.456 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Chile...

  4. 21 CFR 876.5900 - Ostomy pouch and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ostomy pouch and accessories. 876.5900 Section 876.5900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED..., but excludes ostomy pouches which incorporate arsenic-containing compounds. (b) Classification....

  5. Validated Competency Task Lists for Apparel and Accessories Marketing.

    ERIC Educational Resources Information Center

    Selke-Kern, Barbara E.

    Developed by a project that validated task lists by a variety of teachers and apparel marketing business persons, this guide contains task lists for occupations in the field of apparel and accessories marketing. The guide is organized in three sections. Section 1 includes the following: (1) notes on using the information in the guide; (2) a…

  6. 21 CFR 878.4370 - Surgical drape and drape accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Surgical drape and drape accessories. 878.4370 Section 878.4370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4370 Surgical...

  7. 21 CFR 878.4370 - Surgical drape and drape accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Surgical drape and drape accessories. 878.4370 Section 878.4370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4370 Surgical...

  8. 21 CFR 878.4370 - Surgical drape and drape accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Surgical drape and drape accessories. 878.4370 Section 878.4370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4370 Surgical...

  9. 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...

  10. 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...

  11. 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...

  12. 21 CFR 878.4350 - Cryosurgical unit and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 21 CFR 878.4370 - Surgical drape and drape accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Surgical drape and drape accessories. 878.4370 Section 878.4370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4370 Surgical...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 21 CFR 878.4370 - Surgical drape and drape accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Surgical drape and drape accessories. 878.4370 Section 878.4370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4370 Surgical...

  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...

  4. 19 CFR 10.537 - Accessories, spare parts, or tools.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Accessories, spare parts, or tools. 10.537 Section 10.537 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United...

  5. 19 CFR 10.537 - 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. 10.537 Section 10.537 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United...

  6. 19 CFR 10.537 - Accessories, spare parts, or tools.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Accessories, spare parts, or tools. 10.537 Section 10.537 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United...

  7. The sea lamprey has a primordial accessory olfactory system

    PubMed Central

    2013-01-01

    Background A dual olfactory system, represented by two anatomically distinct but spatially proximate chemosensory epithelia that project to separate areas of the forebrain, is known in several classes of tetrapods. Lungfish are the earliest evolving vertebrates known to have this dual system, comprising a main olfactory and a vomeronasal system (VNO). Lampreys, a group of jawless vertebrates, have a single nasal capsule containing two anatomically distinct epithelia, the main (MOE) and the accessory olfactory epithelia (AOE). We speculated that lamprey AOE projects to specific telencephalic regions as a precursor to the tetrapod vomeronasal system. Results To test this hypothesis, we characterized the neural circuits and molecular profiles of the accessory olfactory epithelium in the sea lamprey (Petromyzon marinus). Neural tract-tracing revealed direct and reciprocal connections with the dorsomedial telencephalic neuropil (DTN) which in turn projects directly to the dorsal pallium and the rostral hypothalamus. High-throughput sequencing demonstrated that the main and the accessory olfactory epithelia have virtually identical profiles of expressed genes. Real time quantitative PCR confirmed expression of representatives of all 3 chemoreceptor gene families identified in the sea lamprey genome. Conclusion Anatomical and molecular evidence shows that the sea lamprey has a primordial accessory olfactory system that may serve a chemosensory function. PMID:23957559

  8. 21 CFR 876.4730 - Manual gastroenterology-urology surgical instrument and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... instrument and accessories. 876.4730 Section 876.4730 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Devices § 876.4730 Manual gastroenterology-urology surgical instrument and accessories. (a) Identification. A manual gastroenterology-urology surgical instrument and accessories is a device designed to...

  9. 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

  10. Cloning, expression, and functional characterization of the equine herpesvirus 1 DNA polymerase and its accessory subunit.

    PubMed

    Loregian, Arianna; Case, Alessandro; Cancellotti, Enrico; Valente, Carlo; Marsden, Howard S; Palù, Giorgio

    2006-07-01

    We report the expression and characterization of the putative catalytic subunit (pORF30) and accessory protein (pORF18) of equine herpesvirus 1 DNA polymerase, which are encoded by open reading frames 30 and 18 and are homologous to herpes simplex virus type 1 UL30 and UL42, respectively. In vitro transcription-translation of open reading frames 30 and 18 generated proteins of 136 and 45 kDa, respectively. In vitro-expressed pORF30 possessed basal DNA polymerase activity that was stimulated by pORF18, as measured by DNA polymerase assays in vitro. Purified baculovirus-expressed pORF30 exhibited DNA polymerase activity similar to that of the in vitro-expressed protein, and baculovirus-expressed pORF18 could stimulate both nucleotide incorporation and long-chain DNA synthesis by pORF30 in a dose- and time-dependent manner. The salt optima for activity of both pORF30 and the holoenzyme were substantially different from those for other herpesvirus DNA polymerases. As demonstrated by yeast two-hybrid assays, pORF30 and pORF18 could physically interact, most likely with a 1:1 stoichiometry. Finally, by mutational analysis of the 1,220-residue pORF30, we demonstrated that the extreme C terminus of pORF30 is important for physical and functional interaction with the accessory protein, as reported for UL30 and other herpesvirus DNA polymerases. In addition, a C-proximal region of pORF30, corresponding to residues 1114 to 1172, is involved in binding to, and stimulation by, pORF18. Taken together, the results indicate that pORF30 and pORF18 are the equine herpesvirus 1 counterparts of herpes simplex virus type 1 UL30 and UL42 and share many, but not all, of their characteristics.

  11. Structures of benzylsuccinate synthase elucidate roles of accessory subunits in glycyl radical enzyme activation and activity

    PubMed Central

    Funk, Michael A.; Judd, Evan T.; Marsh, E. Neil G.; Elliott, Sean J.; Drennan, Catherine L.

    2014-01-01

    Anaerobic degradation of the environmental pollutant toluene is initiated by the glycyl radical enzyme benzylsuccinate synthase (BSS), which catalyzes the radical addition of toluene to fumarate, forming benzylsuccinate. We have determined crystal structures of the catalytic α-subunit of BSS with its accessory subunits β and γ, which both bind a [4Fe-4S] cluster and are essential for BSS activity in vivo. We find that BSSα has the common glycyl radical enzyme fold, a 10-stranded β/α-barrel that surrounds the glycyl radical cofactor and active site. Both accessory subunits β and γ display folds related to high potential iron–sulfur proteins but differ substantially from each other in how they interact with the α-subunit. BSSγ binds distally to the active site, burying a hydrophobic region of BSSα, whereas BSSβ binds to a hydrophilic surface of BSSα that is proximal to the active site. To further investigate the function of BSSβ, we determined the structure of a BSSαγ complex. Remarkably, we find that the barrel partially opens, allowing the C-terminal region of BSSα that houses the glycyl radical to shift within the barrel toward an exit pathway. The structural changes that we observe in the BSSαγ complex center around the crucial glycyl radical domain, thus suggesting a role for BSSβ in modulating the conformational dynamics required for enzyme activity. Accompanying proteolysis experiments support these structural observations. PMID:24982148

  12. Spinal accessory neuropathy, droopy shoulder, and thoracic outlet syndrome.

    PubMed

    Al-Shekhlee, Amer; Katirji, Bashar

    2003-09-01

    Droopy shoulder has been proposed as a cause of thoracic outlet syndrome. Two patients developed manifestations of neurovascular compression upon arm abduction, associated with unilateral droopy shoulder and trapezius muscle weakness caused by iatrogenic spinal accessory neuropathies following cervical lymph node biopsies. The first patient developed a cold, numb hand with complete axillary artery occlusion when his arm was abducted to 90 degrees. The second patient complained of paresthesias in digits 4 and 5 of the right hand, worsened by elevation of the arm, with nerve conduction findings of right lower trunk plexopathy (low ulnar and medial antebrachial cutaneous sensory nerve action potentials). Spinal accessory nerve grafting (in the first patient) coupled with shoulder strengthening physical exercises in both patients resulted in gradual improvement of symptoms in 2 years. These two cases demonstrate that unilateral droopy shoulder secondary to trapezius muscle weakness may cause compression of the thoracic outlet structures.

  13. Asymptomatic and isolated accessory mitral valve tissue in an adult.

    PubMed

    Hisatomi, Kazuki; Hashizume, Koji; Tanigawa, Kazuyoshi; Miura, Takashi; Matsukuma, Seiji; Yokose, Shogo; Sumi, Mizuki; Eishi, Kiyoyuki

    2016-02-01

    Accessory mitral valve (AMV) tissue is a congenital anomaly that occurs in association with other congenital anomalies, and is an uncommon cause of left ventricular outflow tract obstruction. It is usually detected in early childhood when accompanied by symptoms of obstruction of the left ventricular outflow tract, and is rarely diagnosed in adults. We present a case of a 53-year-old man who was referred to our institution for evaluation of a systolic heart murmur. Echocardiography disclosed a diagnosis of AMV tissue. This case was uncommon because of the lack of severe obstruction of left ventricular outflow, cardiac symptoms, or other cardiac anomalies. We were able to carry out surgical resection of AMV tissue to avert possible progression of aortic insufficiency and the risk of a cerebrovascular embolization. The patient's postoperative course was uneventful, and postoperative echocardiography showed no residual accessory mitral tissue.

  14. Accessory ossicles and sesamoid bones: recognition and treatment.

    PubMed

    Summers, Anthony

    2015-03-01

    Accessory ossicles and sesamoid bones are normal variants of bone development. In foot and ankle X-rays these bones can appear similar to, or can obscure, fractures, which makes the X-rays difficult to interpret. This article illustrates and describes some of the more common ossicles and sesamoid bones, and provides a brief description of the management of the patients with foot or ankle pain whose X-rays are inconclusive.

  15. Manual examination of accessory movements--seeking R1.

    PubMed

    Petty, N J; Maher, C; Latimer, J; Lee, M

    2002-02-01

    Movement diagrams are used by physiotherapists to depict the behaviour of resistance through the available range of accessory and physiological joint movement. It is generally accepted that for an asymptomatic joint, the resistance first felt by the therapist (R1) occurs towards the end of range. R1 is considered to be at the transition point between the toe and linear region of a load displacement curve. The aim of this study was to more accurately define R1 from force displacement curves of accessory movement to the spine and peripheral joints using a validated instrument, the Spinal Assessment Machine (SAM). Thirty archived force displacement curves obtained using the SAM, which applied a posteroanterior force of 100N at a frequency of 0.5 Hz to L3 spinous process, were examined. In addition force displacement curves were similarly obtained from the tibiofemoral joint, glenohumeral joint and radiocarpal joint of one asymptomatic individual. In all cases resistance to a PA movement commenced at the beginning of range, the curve ascending as soon as the force was applied. While in most cases there was a low stiffness 'toe' region there was no unambiguous point where it could be said that the toe region ended. It is concluded that for spinal and peripheral accessory movements both the onset of resistance and the toe occurs at the beginning of range. Therapists should therefore depict R1 at the beginning of range not toward the end of range as is current practice.

  16. Unusual insidious spinal accessory nerve palsy: a case report

    PubMed Central

    2010-01-01

    Introduction Isolated spinal accessory nerve dysfunction has a major detrimental impact on the functional performance of the shoulder girdle, and is a well-documented complication of surgical procedures in the posterior triangle of the neck. To the best of our knowledge, the natural course and the most effective way of handling spontaneous spinal accessory nerve palsy has been described in only a few instances in the literature. Case presentation We report the case of a 36-year-old Caucasian, Greek man with spontaneous unilateral trapezius palsy with an insidious course. To the best of our knowledge, few such cases have been documented in the literature. The unusual clinical presentation and functional performance mismatch with the imaging findings were also observed. Our patient showed a deterioration that was different from the usual course of this pathology, with an early onset of irreversible trapezius muscle dysfunction two months after the first clinical signs started to manifest. A surgical reconstruction was proposed as the most efficient treatment, but our patient declined this. Although he failed to recover fully after conservative treatment for eight months, he regained moderate function and is currently virtually pain-free. Conclusion Clinicians have to be aware that due to anatomical variation and the potential for compensation by the levator scapulae, the clinical consequences of any injury to the spinal accessory nerve may vary. PMID:20507553

  17. An Accessory Agonist Binding Site Promotes Activation of α4β2* Nicotinic Acetylcholine Receptors*

    PubMed Central

    Wang, Jingyi; Kuryatov, Alexander; Sriram, Aarati; Jin, Zhuang; Kamenecka, Theodore M.; Kenny, Paul J.; Lindstrom, Jon

    2015-01-01

    Neuronal nicotinic acetylcholine receptors containing α4, β2, and sometimes other subunits (α4β2* nAChRs) regulate addictive and other behavioral effects of nicotine. These nAChRs exist in several stoichiometries, typically with two high affinity acetylcholine (ACh) binding sites at the interface of α4 and β2 subunits and a fifth accessory subunit. A third low affinity ACh binding site is formed when this accessory subunit is α4 but not if it is β2. Agonists selective for the accessory ACh site, such as 3-[3-(3-pyridyl)-1,2,4-oxadiazol-5-yl]benzonitrile (NS9283), cannot alone activate a nAChR but can facilitate more efficient activation in combination with agonists at the canonical α4β2 sites. We therefore suggest categorizing agonists according to their site selectivity. NS9283 binds to the accessory ACh binding site; thus it is termed an accessory site-selective agonist. We expressed (α4β2)2 concatamers in Xenopus oocytes with free accessory subunits to obtain defined nAChR stoichiometries and α4/accessory subunit interfaces. We show that α2, α3, α4, and α6 accessory subunits can form binding sites for ACh and NS9283 at interfaces with α4 subunits, but β2 and β4 accessory subunits cannot. To permit selective blockage of the accessory site, α4 threonine 126 located on the minus side of α4 that contributes to the accessory site, but not the α4β2 sites, was mutated to cysteine. Alkylation of this cysteine with a thioreactive reagent blocked activity of ACh and NS9283 at the accessory site. Accessory agonist binding sites are promising drug targets. PMID:25869137

  18. The RED domain of Paired is specifically required for Drosophila accessory gland maturation.

    PubMed

    Li, Li; Li, Ping; Xue, Lei

    2015-02-01

    The evolutionarily conserved paired domain consists of the N-terminal PAI and the C-terminal RED domains, each containing a helix-turn-helix motif capable of binding DNA. Despite its conserved sequence, the physiological functions of the RED domain remain elusive. Here, we constructed a prd transgene expressing a truncated Paired (Prd) protein without the RED domain, and examined its rescue ability in prd mutants. We found that the RED domain is specifically required for the expression of Acp26Aa and sex peptide in male accessory glands, and the induction of female post-mating response. Our data thus identified an important physiological function for the evolutionarily conserved RED domain.

  19. The genome of Rhizobium leguminosarum has recognizable core and accessory components

    PubMed Central

    Young, J Peter W; Crossman, Lisa C; Johnston, Andrew WB; Thomson, Nicholas R; Ghazoui, Zara F; Hull, Katherine H; Wexler, Margaret; Curson, Andrew RJ; Todd, Jonathan D; Poole, Philip S; Mauchline, Tim H; East, Alison K; Quail, Michael A; Churcher, Carol; Arrowsmith, Claire; Cherevach, Inna; Chillingworth, Tracey; Clarke, Kay; Cronin, Ann; Davis, Paul; Fraser, Audrey; Hance, Zahra; Hauser, Heidi; Jagels, Kay; Moule, Sharon; Mungall, Karen; Norbertczak, Halina; Rabbinowitsch, Ester; Sanders, Mandy; Simmonds, Mark; Whitehead, Sally; Parkhill, Julian

    2006-01-01

    Background Rhizobium leguminosarum is an α-proteobacterial N2-fixing symbiont of legumes that has been the subject of more than a thousand publications. Genes for the symbiotic interaction with plants are well studied, but the adaptations that allow survival and growth in the soil environment are poorly understood. We have sequenced the genome of R. leguminosarum biovar viciae strain 3841. Results The 7.75 Mb genome comprises a circular chromosome and six circular plasmids, with 61% G+C overall. All three rRNA operons and 52 tRNA genes are on the chromosome; essential protein-encoding genes are largely chromosomal, but most functional classes occur on plasmids as well. Of the 7,263 protein-encoding genes, 2,056 had orthologs in each of three related genomes (Agrobacterium tumefaciens, Sinorhizobium meliloti, and Mesorhizobium loti), and these genes were over-represented in the chromosome and had above average G+C. Most supported the rRNA-based phylogeny, confirming A. tumefaciens to be the closest among these relatives, but 347 genes were incompatible with this phylogeny; these were scattered throughout the genome but were over-represented on the plasmids. An unexpectedly large number of genes were shared by all three rhizobia but were missing from A. tumefaciens. Conclusion Overall, the genome can be considered to have two main components: a 'core', which is higher in G+C, is mostly chromosomal, is shared with related organisms, and has a consistent phylogeny; and an 'accessory' component, which is sporadic in distribution, lower in G+C, and located on the plasmids and chromosomal islands. The accessory genome has a different nucleotide composition from the core despite a long history of coexistence. PMID:16640791

  20. [Identification of a Novel Calcium (Ca^(2+))-Activated Chloride Channel Accessory Gene in Xenopus laevis].

    PubMed

    Lee, R M; Jeong, S M

    2016-01-01

    Calcium (Ca^(2+))-activated chloride channel accessories (CLCAs) are putative anion channel-related proteins with diverse physiological functions. Exploring CLCA diversity is important for prediction of gene structure and function. In an effort to identify novel CLCA genes in Xenopus laevis, we successfully cloned and characterized a Xenopus laevis cDNA predicted to encode the xCLCA3 gene. Cloning of xCLCA3 was achieved by computational analysis, rapid amplification of cDNA ends (RACE), and a tissue distribution analysis by semi-quantitative reverse transcription (RT) PCR or real-time PCR. We obtained a 2958 bp xCLCA3 cDNA sequence with an open reading frame encoding 943 amino acids. According to the primary structure analysis, xCLCA3 contains a predicted signal sequence, multiple sites of N-linked (N-) glycosylation, N-myristoylation, PKA, PKC, and casein kinase II phosphorylation sites, five putative hydrophobic segments, and the HExxH metalloprotease motif. Additionally, the transmembrane prediction server yielded a preserved N-terminal CLCA domain and a von Willebrand factor type A domain with one transmembrane domain in the C-terminal region. Expression analysis showed that xCLCA3 is expressed in a number of tissues, with strong expression in the brain, colon, small intestine, lung, kidney, and spleen, and poor expression in the heart and liver. These results suggest that xCLCA3 may be a candidate CLCA family member as well as a metalloprotease, rather than just an ion channel accessory protein.

  1. Dynamic Ulnar Drift of Single Digit by an Anomalous Accessory Extensor Tendon.

    PubMed

    Smith, James R A; Amirfeyz, Rouin

    2017-03-01

    Descriptions of multiple extensor slips and accessory extensor tendons of the hand are extensively published in the contemporary literature. Despite their varied anatomy, accessory tendons seldom have a functional implication for the patient. We report a case detailing a previously undescribed accessory extensor tendon of the hand, which resulted unusually in an aberration in the mechanics of a single digit. This was explored and corrected surgically, resulting in an excellent outcome for the patient.

  2. 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.

  3. 26 CFR 48.4061(b)-2 - Definition of parts or accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... automotive speedometers; as well as replacement parts for automobile engines, transmissions, differentials, steering mechanisms, timers, windshild-wiper motors, and other automobile parts or accessories....

  4. 26 CFR 48.4061(b)-2 - Definition of parts or accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... automotive speedometers; as well as replacement parts for automobile engines, transmissions, differentials, steering mechanisms, timers, windshild-wiper motors, and other automobile parts or accessories....

  5. 26 CFR 48.4061(b)-2 - Definition of parts or accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... automotive speedometers; as well as replacement parts for automobile engines, transmissions, differentials, steering mechanisms, timers, windshild-wiper motors, and other automobile parts or accessories....

  6. Bilateral Tensor Fasciae Suralis Muscles in a Cadaver with Unilateral Accessory Flexor Digitorum Longus Muscle

    PubMed Central

    Herrin, Sean O.

    2017-01-01

    Muscle variants are routinely encountered in the dissection laboratory and in clinical practice and therefore anatomists and clinicians need to be aware of their existence. Here we describe two different accessory muscles identified while performing educational dissection of a 51-year-old male cadaver. Tensor fasciae suralis, a rare muscle variant, was identified bilaterally and accessory flexor digitorum longus, a more common muscle variant, was present unilaterally. Tensor fasciae suralis and accessory flexor digitorum longus are clinically relevant muscle variants. To our knowledge, the coexistence of tensor fasciae suralis and accessory flexor digitorum longus in the same individual has not been reported in either cadaveric or imaging studies. PMID:28210274

  7. Bilateral Tensor Fasciae Suralis Muscles in a Cadaver with Unilateral Accessory Flexor Digitorum Longus Muscle.

    PubMed

    Bale, Logan S W; Herrin, Sean O

    2017-01-01

    Muscle variants are routinely encountered in the dissection laboratory and in clinical practice and therefore anatomists and clinicians need to be aware of their existence. Here we describe two different accessory muscles identified while performing educational dissection of a 51-year-old male cadaver. Tensor fasciae suralis, a rare muscle variant, was identified bilaterally and accessory flexor digitorum longus, a more common muscle variant, was present unilaterally. Tensor fasciae suralis and accessory flexor digitorum longus are clinically relevant muscle variants. To our knowledge, the coexistence of tensor fasciae suralis and accessory flexor digitorum longus in the same individual has not been reported in either cadaveric or imaging studies.

  8. The relationship of the accessory navicular to the development of the flat foot.

    PubMed

    Sullivan, J A; Miller, W A

    1979-10-01

    The Kidner procedure has been the most frequently recommended form of surgical treatment for the painful accessory navicular. This formal relocation of the posterior tibial tendon is said to restore the dynamic balance to the foot which is lost when the posterior tibial tendon gives an abnormal insertion into the accessory ossicle. The literature was reviewed to ascertain what is known or what is believed about the accessory navicular and the role of the posterior tibial tendon in the support of the longitudinal arch of the foot. Eighteen patients who had simple excision of the accessory navicular were reviewed to assess the success of such a procedure. In follow-up they all had very satisfactory results. A second group of 208 patients with non-traumatic foot complaints were reviewed to determine the incidence of accessory navicular and its association with the flat foot. Twenty-nine cases of previously undetected accessory navicular were identified in this group giving us a total of 179 patients without accessory navicular and 49 patients with accessory navicular available for study. There was no significant difference between the arch in these 2 groups of patients. Based on the findings in this study, the accessory navicular plays no role in the development of a flat foot. Simple excision of the prominent ossicle seems to be the surgical procedure of choice when conservative means of management fail.

  9. 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

  10. An accessory skull suture mimicking a skull fracture.

    PubMed

    Wiedijk, J E F; Soerdjbalie-Maikoe, V; Maat, G J R; Maes, A; van Rijn, R R; de Boer, H H

    2016-03-01

    This paper describes an investigation of the sudden and unexpected death of a five-and-a-half-month-old boy. As in every Dutch case of sudden unexpected death in infancy (SUDI), a multidisciplinary diagnostic approach was used. This included post-mortem radiography, showing a linear discontinuity of the parietal bone. Originally this was interpreted as a skull fracture, but autopsy indicated no signs of mechanical trauma. Instead the defect was defined as a unilateral accessory suture of the parietal bone. The initial erroneous diagnosis had severe adverse consequences and thus every health care professional or forensic specialist dealing with paediatric mechanical traumas should be cautious of this rare anomaly.

  11. Accessory spleen: differential diagnosis for lymphoma in autoimmune lymphoproliferative syndrome.

    PubMed

    Georgin-Lavialle, Sophie; Aouba, Achille; Canioni, Danielle; Rieux-Laucat, Frédéric; Fischer, Alain; Hermine, Olivier

    2010-07-01

    Mutations of Fas or, less frequently, Fas ligand genes result in a rare inherited lymphoid disorder called autoimmune lymphoproliferative syndrome (ALPS) in which lymphoma frequency is increased. We report on a patient with ALPS who had been splenectomized for giant splenomegaly and progressively developed a voluminous abdominal tumor. The histology of the removed tumor revealed that it was an accessory spleen exhibiting typical features of ALPS involvement, as shown by the presence of a large excess of CD3+CD4-CD8- T cells and plasma cells without a detectable monoclonal population. This observation highlights the lymphoma's differential diagnosis in this context.

  12. 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

  13. [Protein toxins of Staphylococcus aureus].

    PubMed

    Shamsutdinov, A F; Tiurin, Iu A

    2014-01-01

    Main scientific-research studies regarding protein bacterial toxins of the most widespread bacteria that belong to Staphylococcus spp. genus and in particular the most pathogenic species for humans--Staphylococcus aureus, are analyzed. Structural and biological properties of protein toxins that have received the name of staphylococcus pyrogenic toxins (PTSAg) are presented. Data regarding genetic regulation of secretion and synthesis of these toxins and 3 main regulatory genetic systems (agr--accessory gene regulator, xpr--extracellular protein regulator, sar--staphylococcal accessory regulator) that coordinate synthesis of the most important protein toxins and enzymes for virulence of S. aureus, are presented.

  14. Accessory spleen in the pelvis: A case report

    PubMed Central

    Taskin, Mine Islimye; Baser, Banu Guleç; Adali, Ertan; Bulbul, Erdoğan; Uzgoren, Engin

    2015-01-01

    Introduction Accessory Spleen (AS) is a very rare entity and usually near the spleen’s hilum and in the tail of the pancreas. Pelvis reported as an atypical and a rare localization. AS may be formed during embryonic life, they rise from the left side of the dorsal mesogastrium as a result of imperfect fusion of separate splenic masses. Presentation of case We report a case of an AS presenting as an left adnexal mass in a middle-aged woman. Transvaginal ultrasonography and magnetic resonance imaging (MRI) revealed a left adnexial mass. Laparatomy was performed, and histological examination revealed that resected mass was splenic tissue. Discussion An AS is an incidental finding of no clinical significance in most patients. AS are generally determined during radiological investigations or during open or laparoscopic surgeries. When, the AS settle in the adnexal area; the differential diagnosis could include the causes of adnexal masses like enlarged lymph nodes, subserous fibroid, ovarian tumors, organized hematoma, tuboovarian abscess. Conclusion Althought pelvic accessory spleen is a rare condition, should be considered in the differential diagnosis of adnexal masses. PMID:25985297

  15. Hidden female physiological resistance to male accessory gland substances in a simultaneous hermaphrodite

    PubMed Central

    Koene, Joris M.

    2017-01-01

    ABSTRACT To increase fertilization chances compared with rivals, males are favoured to transfer accessory gland proteins to females during mating. These substances, by influencing female physiology, cause alteration of her sperm usage and remating rate. Simultaneously hermaphroditic land snails with love-darts are a case in point. During courtship, a love-dart is pierced through the partner's body wall, thereby introducing accessory mucous gland products. This mucus physiologically increases paternity by inhibiting the digestion of donated sperm. The sperm, which are packaged in a spermatophore, are exchanged and received in an organ called the diverticulum. Because of its length, this organ was previously proposed to be a female anatomical adaptation that may limit the dart interference with the recipient's sperm usage. For reproductive success of the donor, an anatomically long spermatophore, relative to the partner's diverticulum, is beneficial as sperm can avoid digestion by exiting through the spermatophore's tail safely. However, the snail Eobania vermiculata possesses a diverticulum that is three times longer than the spermatophore it receives. Here, we report that the love-dart mucus of this species contains a contraction-inducing substance that shortens the diverticulum, an effect that is only properly revealed when the mucus is applied to another helicid species, Cornu aspersum. This finding suggests that E. vermiculata may have evolved a physiological resistance to the manipulative substance received via the love-dart by becoming insensitive to it. This provides useful insight into the evolution of female resistance to male manipulations, indicating that it can remain hidden if tested on a single species. PMID:28062580

  16. Identification and characterization of a cell surface marker for embryonic rat spinal accessory motor neurons.

    PubMed

    Schubert, W; Kaprielian, Z

    2001-10-22

    The developing mammalian spinal cord contains distinct populations of motor neurons that can be distinguished by their cell body positions, by the expression of specific combinations of regulatory genes, and by the paths that their axons take to exit the central nervous system (CNS). Subclasses of spinal motor neurons are also thought to express specific cell surface proteins that function as receptors which control the guidance of their axons. We identified monoclonal antibody (mAb) SAC1 in a screen aimed at generating markers for specific subsets of neurons/axons in the developing rat spinal cord. During early embryogenesis, mAb SAC1 selectively labels a small subset of Isl1-positive motor neurons located exclusively within cervical segments of the spinal cord. Strikingly, these neurons extend mAb SAC1-positive axons along a dorsally directed trajectory toward the lateral exit points. Consistent with the finding that mAb SAC1 also labels spinal accessory nerves, these observations identify mAb SAC1 as a specific marker of spinal accessory motor neurons/axons. During later stages of embryogenesis, mAb SAC1 is transiently expressed on both dorsally and ventrally projecting spinal motor neurons/axons. Interestingly, mAb SAC1 also labels the notochord and floor plate during most stages of spinal cord development. The mAb SAC1 antigen is a 100-kD glycoprotein that is likely to be the rat homolog of SC1/BEN/DM-GRASP, a homophilic adhesion molecule that mediates axon outgrowth and fasciculation.

  17. Decontamination of minimally invasive surgical endoscopes and accessories.

    PubMed

    Ayliffe, G

    2000-08-01

    (1) Infections following invasive endoscopy are rare and are usually of endogenous origin. Nevertheless, infections do occur due to inadequate cleaning and disinfection and the use of contaminated rinse water and processing equipment. (2) Rigid and flexible operative endoscopes and accessories should be thoroughly cleaned and preferably sterilized using properly validated processes. (3) Heat tolerant operative endoscopes and accessories should be sterilized using a vacuum assisted steam sterilizer. Use autoclavable instrument trays or containers to protect equipment during transit and processing. Small bench top sterilizers without vacuum assisted air removal are unsuitable for packaged and lumened devices. (4) Heat sensitive rigid and flexible endoscopes and accessories should preferably be sterilized using ethylene oxide, low temperature steam and formaldehyde (rigid only) or gas plasma (if appropriate). (5) If there are insufficient instruments or time to sterilize invasive endoscopes, or if no suitable method is available locally, they may be disinfected by immersion in 2% glutaraldehyde or a suitable alternative. An immersion time of at least 10 min should be adopted for glutaraldehyde. This is sufficient to inactivate most vegetative bacteria and viruses including HIV and hepatitis B virus (HBV). Longer contact times of 20 min or more may be necessary if a mycobacterial infection is known or suspected. At least 3 h immersion in glutaraldehyde is required to kill spores. (6) Glutaraldehyde is irritant and sensitizing to the skin, eyes and respiratory tract. Measures must be taken to ensure glutaraldehyde is used in a safe manner, i.e., total containment and/or extraction of harmful vapour and the provision of suitable personal protective equipment, i.e., gloves, apron and eye protection if splashing could occur. Health surveillance of staff is recommended and should include a pre-employment enquiry regarding asthma, skin and mucosal sensitivity problems and

  18. Detection and sequence analysis of accessory gene regulator genes of Staphylococcus pseudintermedius isolates

    PubMed Central

    Chitra, M. Ananda; Jayanthy, C.; Nagarajan, B.

    2015-01-01

    Background: Staphylococcus pseudintermedius (SP) is the major pathogenic species of dogs involved in a wide variety of skin and soft tissue infections. The accessory gene regulator (agr) locus of Staphylococcus aureus has been extensively studied, and it influences the expression of many virulence genes. It encodes a two-component signal transduction system that leads to down-regulation of surface proteins and up-regulation of secreted proteins during in vitro growth of S. aureus. The objective of this study was to detect and sequence analyzing the AgrA, B, and D of SP isolated from canine skin infections. Materials and Methods: In this study, we have isolated and identified SP from canine pyoderma and otitis cases by polymerase chain reaction (PCR) and confirmed by PCR-restriction fragment length polymorphism. Primers for SP agrA and agrBD genes were designed using online primer designing software and BLAST searched for its specificity. Amplification of the agr genes was carried out for 53 isolates of SP by PCR and sequencing of agrA, B, and D were carried out for five isolates and analyzed using DNAstar and Mega5.2 software. Results: A total of 53 (59%) SP isolates were obtained from 90 samples. 15 isolates (28%) were confirmed to be methicillin-resistant SP (MRSP) with the detection of the mecA gene. Accessory gene regulator A, B, and D genes were detected in all the SP isolates. Complete nucleotide sequences of the above three genes for five isolates were submitted to GenBank, and their accession numbers are from KJ133557 to KJ133571. AgrA amino acid sequence analysis showed that it is mainly made of alpha-helices and is hydrophilic in nature. AgrB is a transmembrane protein, and AgrD encodes the precursor of the autoinducing peptide (AIP). Sequencing of the agrD gene revealed that the 5 canine SP strains tested could be divided into three Agr specificity groups (RIPTSTGFF, KIPTSTGFF, and RIPISTGFF) based on the putative AIP produced by each strain. The AIP of

  19. 21 CFR 876.5880 - Isolated kidney perfusion and transport system and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Isolated kidney perfusion and transport system and....5880 Isolated kidney perfusion and transport system and accessories. (a) Identification. An isolated kidney perfusion and transport system and accessories is a device that is used to support a donated or...

  20. 21 CFR 876.5880 - Isolated kidney perfusion and transport system and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Isolated kidney perfusion and transport system and....5880 Isolated kidney perfusion and transport system and accessories. (a) Identification. An isolated kidney perfusion and transport system and accessories is a device that is used to support a donated or...

  1. 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.

  2. 21 CFR 882.4300 - Manual cranial drills, burrs, trephines, and their accessories

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Manual cranial drills, burrs, trephines, and their... Manual cranial drills, burrs, trephines, and their accessories (a) Identification. Manual cranial drills, burrs, trephines, and their accessories are bone cutting and drilling instruments that are used...

  3. 21 CFR 888.4580 - Sonic surgical instrument and accessories/attachments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .../attachments. 888.4580 Section 888.4580 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... instrument and accessories/attachments. (a) Identification. A sonic surgical instrument is a hand-held device with various accessories or attachments, such as a cutting tip that vibrates at high frequencies,...

  4. 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....

  5. 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....

  6. 48 CFR 52.247-13 - Accessorial Services-Moving Contracts.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...-Moving Contracts. 52.247-13 Section 52.247-13 Federal Acquisition Regulations System FEDERAL ACQUISITION... Clauses 52.247-13 Accessorial Services—Moving Contracts. As prescribed in 47.207-5(c), insert a clause... furniture: Accessorial Services—Moving Contracts (APR 1984) (a) Packing and/or crating and padding....

  7. 48 CFR 52.247-13 - Accessorial Services-Moving Contracts.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...-Moving Contracts. 52.247-13 Section 52.247-13 Federal Acquisition Regulations System FEDERAL ACQUISITION... Clauses 52.247-13 Accessorial Services—Moving Contracts. As prescribed in 47.207-5(c), insert a clause... furniture: Accessorial Services—Moving Contracts (APR 1984) (a) Packing and/or crating and padding....

  8. 48 CFR 52.247-13 - Accessorial Services-Moving Contracts.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...-Moving Contracts. 52.247-13 Section 52.247-13 Federal Acquisition Regulations System FEDERAL ACQUISITION... Clauses 52.247-13 Accessorial Services—Moving Contracts. As prescribed in 47.207-5(c), insert a clause... furniture: Accessorial Services—Moving Contracts (APR 1984) (a) Packing and/or crating and padding....

  9. 48 CFR 52.247-13 - Accessorial Services-Moving Contracts.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...-Moving Contracts. 52.247-13 Section 52.247-13 Federal Acquisition Regulations System FEDERAL ACQUISITION... Clauses 52.247-13 Accessorial Services—Moving Contracts. As prescribed in 47.207-5(c), insert a clause... furniture: Accessorial Services—Moving Contracts (APR 1984) (a) Packing and/or crating and padding....

  10. 48 CFR 52.247-13 - Accessorial Services-Moving Contracts.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...-Moving Contracts. 52.247-13 Section 52.247-13 Federal Acquisition Regulations System FEDERAL ACQUISITION... Clauses 52.247-13 Accessorial Services—Moving Contracts. As prescribed in 47.207-5(c), insert a clause... furniture: Accessorial Services—Moving Contracts (APR 1984) (a) Packing and/or crating and padding....

  11. 21 CFR 884.1300 - Uterotubal carbon dioxide insufflator and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 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...

  12. Intermittent torsion of accessory hepatic lobe: An unusual cause of recurrent right upper quadrant pain.

    PubMed

    Jambhekar, Kedar; Pandey, Tarun; Kaushik, Chhavi; Shah, Hemendra R

    2010-05-01

    An accessory lobe of the liver is a rare congenital anomaly that can undergo torsion and present as an acute surgical emergency. It is rarely diagnosed preoperatively. We report the preoperative utility of CT scan and MRI in the diagnosis and surgical planning of a case of intermittent accessory hepatic lobe torsion.

  13. 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...

  14. 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...

  15. 21 CFR 874.4710 - Esophagoscope (flexible or rigid) and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Surgical Devices § 874.4710... accessories is a tubular endoscopic device with any of a group of accessory devices which attach to the... disease, or to remove foreign bodies from the esophagus. When inserted, the device extends from the...

  16. 21 CFR 874.4760 - Nasopharyngoscope (flexible or rigid) and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Surgical Devices § 874.4760...) and accessories is a tubular endoscopic device with any of a group of accessory devices which attach to the nasopharyngoscope and is intended to examine or treat the nasal cavity and nasal pharynx....

  17. 21 CFR 874.4710 - Esophagoscope (flexible or rigid) and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Surgical Devices § 874.4710... accessories is a tubular endoscopic device with any of a group of accessory devices which attach to the... disease, or to remove foreign bodies from the esophagus. When inserted, the device extends from the...

  18. 21 CFR 874.4760 - Nasopharyngoscope (flexible or rigid) and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Surgical Devices § 874.4760...) and accessories is a tubular endoscopic device with any of a group of accessory devices which attach to the nasopharyngoscope and is intended to examine or treat the nasal cavity and nasal pharynx....

  19. 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...

  20. 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...

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 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...

  2. 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...

  3. 77 FR 67261 - Airworthiness Directives; Aeronautical Accessories, Inc., High Landing Gear Forward Crosstube...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-09

    ... Accessories, Inc., High Landing Gear Forward Crosstube Assembly AGENCY: Federal Aviation Administration (FAA... Accessories, Inc. (AAI) high landing gear forward crosstube assemblies (crosstubes) installed on Agusta S.p.A..., collapse of the landing gear, and subsequent loss of control of the helicopter. DATES: This AD is...

  4. 77 FR 27663 - Airworthiness Directives; Aeronautical Accessories, Inc. High Landing Gear Forward Crosstube...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-11

    ... Accessories, Inc. High Landing Gear Forward Crosstube Assembly AGENCY: Federal Aviation Administration (FAA... directive (AD) for Aeronautical Accessories, Inc. (AAI) high landing gear forward crosstube assemblies... crosstubes. The proposed actions are intended to prevent failure of a crosstube, collapse of the landing...

  5. 77 FR 5420 - Airworthiness Directives; Aeronautical Accessories Inc. High Landing Gear Aft Crosstube Assembly

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-03

    ... Accessories Inc. High Landing Gear Aft Crosstube Assembly AGENCY: Federal Aviation Administration (FAA), DOT... (AD) for the Aeronautical Accessories Inc. (AAI) High Landing Gear Aft Crosstube Assembly (aft... proposed actions are intended to prevent failure of a crosstube, collapse of the landing gear,...

  6. Effect of Accessory Power Take-off Variation on a Turbofan Engine Performance

    DTIC Science & Technology

    2012-09-26

    EFFECT OF ACCESSORY POWER TAKE-OFF VARIATION ON A TURBOFAN ENGINE PERFORMANCE THESIS...ACCESSORY POWER TAKE-OFF VARIATIONS ON A TURBOFAN ENGINE PERFORMANCE DISSERTATION Presented to the Faculty Department of Aeronautics and...TURBOFAN ENGINE PERFORMANCE Anis Faidi, BS 1st Lieutenant, TUNAF Approved

  7. 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

  8. 21 CFR 876.4730 - Manual gastroenterology-urology surgical instrument and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Manual gastroenterology-urology surgical... Devices § 876.4730 Manual gastroenterology-urology surgical instrument and accessories. (a) Identification. A manual gastroenterology-urology surgical instrument and accessories is a device designed to...

  9. Component-dependent urine responses in the rat accessory olfactory bulb.

    PubMed

    Sugai, Tokio; Yoshimura, Hiroshi; Kato, Nobuo; Onoda, Norihiko

    2006-11-06

    To investigate how pheromonal information is processed in the rat accessory olfactory bulb, we optically imaged intrinsic signals to obtain high-resolution maps of activation induced by urinary stimulation. Application of volatile components in male urine mainly induced activation in the anterior accessory olfactory bulb, irrespective of the sex, whereas volatile female urine elicited activation not only in the anterior but also to some extent in the caudal part of the posterior accessory olfactory bulb of male, but not female, rats. Nonvolatile components of both male and female urine induced activation mainly in the rostral part of the posterior and to a lesser extent in the anterior accessory olfactory bulb, irrespective of the sex. These results indicate that volatile and nonvolatile urinary components activate the anterior and posterior subdivisions of the accessory olfactory bulb, respectively.

  10. Suppression subtractive hybridization analysis reveals expression of conserved and novel genes in male accessory glands of the ant Leptothorax gredleri

    PubMed Central

    2010-01-01

    Background During mating, insect males eject accessory gland proteins (Acps) into the female genital tract. These substances are known to affect female post-mating behavior and physiology. In addition, they may harm the female, e.g., in reducing its lifespan. This is interpreted as a consequence of sexual antagonistic co-evolution. Whereas sexual conflict abounds in non-social species, the peculiar life history of social insects (ants, bees, wasps) with lifelong pair-bonding and no re-mating aligns the reproductive interests of the sexes. Harming the female during mating would negatively affect male fitness and sexual antagonism is therefore not expected. Indeed, mating appears to increase female longevity in at least one ant species. Acps are presumed to play a role in this phenomenon, but the underlying mechanisms are unknown. In this study, we investigated genes, which are preferentially expressed in male accessory glands of the ant Leptothorax gredleri, to determine which proteins might be transferred in the seminal fluid. Results By a suppression subtractive hybridization protocol we obtained 20 unique sequences (USs). Twelve had mutual best matches with genes predicted for Apis mellifera and Nasonia vitripennis. Functional information (Gene Ontology) was available only for seven of these, including intracellular signaling, energy-dependent transport and metabolic enzyme activities. The remaining eight USs did not match sequences from other species. Six genes were further analyzed by quantitative RT-PCR in three life cycle stages of male ants. A gene with carboxy-lyase activity and one of unpredicted function were significantly overexpressed in accessory glands of sexually mature males. Conclusions Our study is the first one to investigate differential gene expression in ants in a context related to mating. Our findings indicate that male accessory glands of L. gredleri express a series of genes that are unique to this species, possibly representing novel

  11. 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.

  12. Intrapancreatic Accessory Spleen: A Diagnosis Not to Forget!

    PubMed Central

    Marques, Susana; Bispo, Miguel; Noia, Lariño

    2016-01-01

    A 69-year-old male patient was incidentally diagnosed with a 5-mm lesion in the pancreatic tail by endoscopic ultrasound (EUS). After contrast-enhanced EUS and EUS-elastography, all imaging features were highly suggestive of a benign pancreatic solid lesion such as an intrapancreatic accessory spleen (IPAS) or a benign neuroendocrine tumor. Interposition of the splenic artery precluded EUS-guided fine-needle aspiration (FNA). When an asymptomatic pancreatic mass is detected, IPAS diagnosis should be considered, and, if EUS-FNA is infeasible, contrast-enhanced EUS and EUS-elastography are useful tools to differentiate a pancreatic benign lesion as IPAS from a malignancy, with avoidance of unnecessary surgery. PMID:28100996

  13. Evolution of the continental crust as recorded in accessory minerals

    NASA Astrophysics Data System (ADS)

    Iizuka, Tsuyoshi

    2013-04-01

    Recent developments in precise in situ isotopic analysis by LA-ICPMS and SIMS allow correlating multiple isotopic systems within single grains of accessory minerals such as zircon and monazite. The combined isotope systematics have provided valuable insights into the evolution of the continental crust. Zircon, a common accessory phase in granitoids, can be precisely dated by the U-Pb system. Zircon Lu-Hf isotopic composition is a function of crustal residence time of the magmatic protolith, whereas the O isotopic composition is a sensitive record of reworking of mature sediments such as pelite. An integration of U-Pb, Lu-Hf and O isotopic data for detrital zircons from modern large rivers indicates that: (1) the preserved continental crust dominantly formed between 3.6 and 1.0 Ga, (2) the major mode of crustal development would change during the supercontinent cycle, i.e., the generation of juvenile crust during supercontinent fragmentation versus the stabilization of the generated crust via crustal remelting during supercontinent fragmentation, and (3) reworking of mature sediments increased abruptly at ca. 2.1 Ga. No granitoids are known to have survived since 4.03 Ga. Yet evidence of an even older evolved crust is provided by detrital zircons with ages up to 4.4 Ga from Mt. Narryer and Jack Hills metasedimentary rocks in the Yilgarn Craton, Western Australia. Recently, such Hadean zircons have been found from outside the Yilgarn Craton, indicating that the young Earth had widespread granitoid crust. In addition, another accessory phase, monazite, in the Mt. Narryer and Jack Hills metasedimentary rocks offers an unique opportunity to advance our knowledge of early crustal evolution. Monazite, a light rare earth element phosphate mineral, occurs as an igneous accessory phase particularly in low-Ca granitoids, in contrast to the occurrence of igneous zircon in a wide range of granitoids. U-Pb and Sm-Nd isotope systematic of monazite are analogous to U-Pb and Lu

  14. Accessory Upper Subscapular Nerve – The Neurotisation Tool

    PubMed Central

    Deshmukh, Vishwajit Ravindra; Mandal, Rabindra Prasad; Kusuma, Harisha

    2016-01-01

    During the routine dissection classes for undergraduate students, uncommon variation in relation to the upper subscapular nerve of posterior cord of brachial plexus was observed. Normally upper subscapular nerve takes origin from the posterior cord, but in this case report, it arises in triplet fashion, just above the circumflex scapular artery. All these accessory nerves were supplying upper part of the subscapularis muscle. As per our knowledge, this is a rare variation of brachial plexus. Many variations are encountered in the formation of brachial plexus. The normal and the abnormal origin of nerves are important considering neurotisation surgeries as well as during the infraclavicular nerve block for various axillary and upper limb surgeries. PMID:27790416

  15. Silicone-based stoma accessories in clinical practice.

    PubMed

    Cronin, Elaine

    Advanced silicone technology has transformed the treatment of wounds and peri-wound skin. Recently, there has been interest in the use of silicone-based products in stoma care. Peristomal skin issues are a common problem, and can have a negative impact on the patient's quality of life, so helping the ostomate maintain good skin health is crucial. The author, a stoma care nurse, regularly sees 3-4 patients each week in her stoma care clinic with damaged or broken peristomal skin. This article explores the 'Trio' range of silicone-based accessories, discussing how these products compare with the traditional hydrocolloid, how they are applied and used. A series of case studies illustrates the circumstances in which these products may be applied.

  16. Accessory pathway for sound transfer in a neotropical frog.

    PubMed Central

    Narins, P M; Ehret, G; Tautz, J

    1988-01-01

    A portion of the lateral body wall overlying the lung cavity of the arboreal frog, Eleutherodactylus coqui, vibrates in response to free-field sound. Peak displacement amplitude of the body wall in response to a natural call note presented at 73 decibels sound pressure level is 1.70 X 10(-9) m, roughly 8 decibels less than that of the ipsilateral eardrum, as measured by laser Doppler vibrometry. We show that the vibration magnitude varies predictably across the body profile and is posture and frequency dependent. Two routes to the inner ear are described for sounds impinging on the body wall; either of these accessory pathways could modify direct input from the peripheral auditory system and enhance sound localization in these small vertebrates. PMID:3422747

  17. New Scopes, New Accessories, New Stents for Interventional Endoscopic Ultrasound

    PubMed Central

    Chapman, Christopher G.; Siddiqui, Uzma D.

    2016-01-01

    Technological advances have rapidly expanded the therapeutic potential of endoscopic ultrasound (EUS). Innovations in stent technology; directed adjunctive therapy for pancreatic tumors, including radiofrequency ablation and fiducial marker placement; advanced imaging modalities, including needle-based confocal laser endomicroscopy; and new echoendoscopes, such as the forward-viewing linear echoendoscope, are emerging as safe and effective tools and devices for providing a broad range of treatments and therapies previously not thought possible. In this review, we summarize and discuss the new echoendoscopes, accessories, and stents for interventional EUS and highlight the recent literature on technical and therapeutic efficacy. The therapeutic role and indications for EUS are rapidly evolving well beyond its current limits as new EUS-specific designed tools are designed, and ultimately, should help achieve the goal of improving patient outcomes. PMID:26855923

  18. Development of Heat-resistant XLPE Cable and Accessories

    NASA Astrophysics Data System (ADS)

    Yamada, Hiroyuki; Nakagawa, Shinichi; Murata, Yoshinao; Kishi, Kouji; Katakai, Shoshi

    We have developed heat-resistant XLPE cable and accessories that can be operated at 105°C as the maximum permissible conductor temperature in normal operation. Through this cable system, greater transmission capacity can be achieved using existing cable ducts and without increasing the conductor size of the cable. We have developed heat-resistant XLPE insulation material which has a higher melting point than that of conventional XLPE. The breakdown strength of heat-resistant XLPE cable at 105°C is almost the same as that of conventional XLPE cable at 90°C. The heat deformation of the new cable at 105°C is almost the same as that of conventional XLPE cable at 90°C. Conventional self-pressurized rubber joints can be applied to heat-resistant cable lines with the new waterproof joint compound with low heat resistivity.

  19. Identification and significance of accessory minerals from a bituminous coal

    USGS Publications Warehouse

    Finkelman, R.B.; Stanton, R.W.

    1978-01-01

    A scanning electron microscope (SEM) has been used to study the in situ accessory minerals in polished blocks and pellets of petrographically analysed samples of the Waynesburg coal (hvb). Individual grains from the low-temperature ash (LTA) of the same coal were also studied. The visual resolution of the SEM permitted the detection of submicron mineral grains, which could then be analysed by the attached energy-dispersive system. Emphasis was placed on the highly reflective grains in the carbominerite bands. Among the most abundant accessory minerals observed were rutile, zircon, and rare-earth-bearing minerals. Small (1-5 ??m) particles of what may be authigenic iron-rich chromite and a nickel silicate form rims on quartz grains. The SEM also permits the observation of grain morphology and mineral intergrowths. These data are useful in determining authigenicity and diagenic alteration. Substances in density splits of LTA include authigenic, detrital, extraterrestrial magnetite, tourmaline, and evaporite (?) minerals, and a fluorine-bearing amphibole. This analytical approach allows the determination of specific sites for many of the trace elements in coals. In the Waynesburg coal, most of the chromium is in the iron-chromium rims, the fluorine is in the amphibole, and the rare-earth elements are in rare-earth-bearing minerals. The ability to relate trace-element data to specific minerals will aid in predicting the behaviour of elements in coal during combustion, liquefaction, gasification, weathering, and leaching processes. This ability also permits insight into the degree of mobility of these elements in coal and provides clues to sedimentological and diagenetic conditions. ?? 1978.

  20. Role of N-Terminal Domain and Accessory Subunits in Controlling Deactivation-Inactivation Coupling of Kv4.2 Channels

    PubMed Central

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

    2008-01-01

    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 Kv4.2Δ2–10 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 Kv4.2Δ2–10 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. PMID:17981906