WorldWideScience

Sample records for clade-c trimeric gp140

  1. Characterization of humoral responses to soluble trimeric HIV gp140 from a clade A Ugandan field isolate

    DEFF Research Database (Denmark)

    Visciano, Maria Luisa; Tagliamonte, Maria; Stewart-Jones, Guillaume;

    2013-01-01

    neutralizing activity against homologous and heterologous viruses. In the present study, we generated a recombinant trimeric soluble gp140, derived from a previously identified Ugandan A-clade HIV field isolate (gp14094UG018). Antibodies elicited in immunized rabbits show a broad binding pattern to HIV......Trimeric soluble forms of HIV gp140 envelope glycoproteins represent one of the closest molecular structures compared to native spikes present on intact virus particles. Trimeric soluble gp140 have been generated by several groups and such molecules have been shown to induce antibodies with...

  2. Effect of trimerization motifs on quaternary structure, antigenicity, and immunogenicity of a noncleavable HIV-1 gp140 envelope glycoprotein

    International Nuclear Information System (INIS)

    The external domains of the HIV-1 envelope glycoprotein (gp120 and the gp41 ectodomain, collectively known as gp140) contain all known viral neutralization epitopes. Various strategies have been used to create soluble trimers of the envelope to mimic the structure of the native viral protein, including mutation of the gp120-gp41 cleavage site, introduction of disulfide bonds, and fusion to heterologous trimerization motifs. We compared the effects on quaternary structure, antigenicity, and immunogenicity of three such motifs: T4 fibritin, a GCN4 variant, and the Escherichia coli aspartate transcarbamoylase catalytic subunit. Fusion of each motif to the C-terminus of a noncleavable JRCSF gp140(-) envelope protein led to enhanced trimerization but had limited effects on the antigenic profile and CD4-binding ability of the trimers. Immunization of rabbits provided no evidence that the trimerized gp140(-) constructs induced significantly improved neutralizing antibodies to several HIV-1 pseudoviruses, compared to gp140 lacking a trimerization motif. However, modest differences in both binding specificity and neutralizing antibody responses were observed among the various immunogens.

  3. Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability

    Science.gov (United States)

    Kong, Leopold; He, Linling; de Val, Natalia; Vora, Nemil; Morris, Charles D.; Azadnia, Parisa; Sok, Devin; Zhou, Bin; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.; Zhu, Jiang

    2016-06-01

    The trimeric HIV-1 envelope glycoprotein (Env) is critical for host immune recognition and neutralization. Despite advances in trimer design, the roots of Env trimer metastability remain elusive. Here we investigate the contribution of two Env regions to metastability. First, we computationally redesign a largely disordered bend in heptad region 1 (HR1) of SOSIP trimers that connects the long, central HR1 helix to the fusion peptide, substantially improving the yield of soluble, well-folded trimers. Structural and antigenic analyses of two distinct HR1 redesigns confirm that redesigned Env closely mimics the native, prefusion trimer with a more stable gp41. Next, we replace the cleavage site between gp120 and gp41 with various linkers in the context of an HR1 redesign. Electron microscopy reveals a potential fusion intermediate state for uncleaved trimers containing short but not long linkers. Together, these results outline a general approach for stabilization of Env trimers from diverse HIV-1 strains.

  4. Memory B cell antibodies to HIV-1 gp140 cloned from individuals infected with clade A and B viruses.

    Directory of Open Access Journals (Sweden)

    Hugo Mouquet

    Full Text Available Understanding the antibody response to HIV-1 in humans that show broad neutralizing serologic activity is a crucial step in trying to reproduce such responses by vaccination. Investigating antibodies with cross clade reactivity is particularly important as these antibodies may target conserved epitopes on the HIV envelope gp160 protein. To this end we have used a clade B YU-2 gp140 trimeric antigen and single-cell antibody cloning methods to obtain 189 new anti-gp140 antibodies representing 51 independent B cell clones from the IgG memory B cells of 3 patients infected with HIV-1 clade A or B viruses and exhibiting broad neutralizing serologic activity. Our results support previous findings showing a diverse antibody response to HIV gp140 envelope protein, characterized by differentially expanded B-cell clones producing highly hypermutated antibodies with heterogenous gp140-specificity and neutralizing activity. In addition to their high-affinity binding to the HIV spike, the vast majority of the new anti-gp140 antibodies are also polyreactive. Although none of the new antibodies are as broad or potent as VRC01 or PG9, two clonally-related antibodies isolated from a clade A HIV-1 infected donor, directed against the gp120 variable loop 3, rank in the top 5% of the neutralizers identified in our large collection of 185 unique gp140-specific antibodies in terms of breadth and potency.

  5. Comparative Immunogenicity of HIV-1 gp140 Vaccine Delivered by Parenteral, and Mucosal Routes in Female Volunteers; MUCOVAC2, A Randomized Two Centre Study.

    Directory of Open Access Journals (Sweden)

    Catherine A Cosgrove

    Full Text Available Defining optimal routes for induction of mucosal immunity represents an important research priority for the HIV-1 vaccine field. In particular, it remains unclear whether mucosal routes of immunization can improve mucosal immune responses.In this randomized two center phase I clinical trial we evaluated the systemic and mucosal immune response to a candidate HIV-1 Clade C CN54gp140 envelope glycoprotein vaccine administered by intramuscular (IM, intranasal (IN and intravaginal (IVAG routes of administration in HIV negative female volunteers. IM immunizations were co-administered with Glucopyranosyl Lipid Adjuvant (GLA, IN immunizations with 0.5% chitosan and IVAG immunizations were administered in an aqueous gel.Three IM immunizations of CN54 gp140 at either 20 or 100 μg elicited significantly greater systemic and mucosal antibodies than either IN or IVAG immunizations. Following additional intramuscular boosting we observed an anamnestic antibody response in nasally primed subjects. Modest neutralizing responses were detected against closely matched tier 1 clade C virus in the IM groups. Interestingly, the strongest CD4 T-cell responses were detected after IN and not IM immunization.These data show that parenteral immunization elicits systemic and mucosal antibodies in women. Interestingly IN immunization was an effective prime for IM boost, while IVAG administration had no detectable impact on systemic or mucosal responses despite IM priming.EudraCT 2010-019103-27 and the UK Clinical Research Network (UKCRN Number 11679.

  6. gp140, the C3d receptor of human B lymphocytes, is also the Epstein-Barr virus receptor.

    OpenAIRE

    Frade, R; Barel, M; Ehlin-Henriksson, B.; Klein, G

    1985-01-01

    The relationship between gp140, the membrane C3d receptor (CR2) of human B lymphocytes, and the Epstein-Barr virus receptor (EBVR) was analyzed by using the polyclonal anti-gp140, previously prepared by immunizing rabbits with highly purified gp140 (isolated by some of us) from CR2/EBVR-positive Raji cells. Polyclonal anti-gp72, a C3-binding membrane component, not related to the EBVR but also expressed on the Raji cell surface, was used as a control. Binding of rabbit IgG and EBV on cells wa...

  7. Construction of a recombinant HIV-1 gp140 protein vaccine and evaluation of its immunogenicity%HIV-1 gp140蛋白疫苗的设计及其免疫原性研究

    Institute of Scientific and Technical Information of China (English)

    宋伟; 刘建东; 葛向阳; 任莉; 邵一鸣; 郝彦玲

    2016-01-01

    目的 设计HIV-1 gp140蛋白疫苗并进行免疫原性初步研究.方法 构建包含不同信号肽的gp140蛋白表达克隆,对表达效率和信号肽切割效率进行比较筛选,同时对不同长度C末端的gp140进行比较,最终获得优化的HIV-1 gp140免疫原.采用不同的免疫方式免疫豚鼠,通过特异性结合抗体检测和中和抗体检测进行免疫效果评价.结果 设计的信号肽具有较好的分泌、切割效率,重组HIV-1 gp140抗原获得良好的表达.重组蛋白疫苗单独免疫就能诱导很强的结合抗体和中和抗体反应,反应强度高于重组DNA疫苗以及痘苗病毒载体疫苗的联合免疫.不同C末端长度的gp140蛋白免疫效果没有显著的差异,但长C末端的gp140蛋白免疫效果稍好.结论 优化设计了HIV-1 gp140蛋白疫苗,设计的重组疫苗获得较好的免疫效果.%Objective To construct a recombinant HIV-1 gp140 protein vaccine and to evaluate its immunogenicity.Methods Four expression vectors containing different signal peptides including DRVI, IL-2, venom and chitinase were constructed for the expression of gp140 protein clones.Western blot assay was per-formed to evaluate the expression efficiency of the constructed expression vectors.The cleavage of signal peptides was analyzed by sequencing analysis.The gp140 protein clones with different lengths of C-terminus were con-structed and then comparatively analyzed for the screening of optimized recombinant HIV-1 gp140 antigen. Guinea pigs were immunized with different strategies and the potency of vaccination was evaluated by detecting the binding antibodies and neutralizing antibodies after immunization.Results DRVI, the designed signal pep-tide, had the advantages in determining the efficiency of protein secretion and signal peptide cleavage.Com-pared with the co-immunization with DNA and recombinant Tiantan vaccinia HIV vaccines, immunization of guinea pigs with the recombined gp140 protein vaccine alone could

  8. gp140, the C3d receptor of human B lymphocytes, is also the Epstein-Barr virus receptor.

    Science.gov (United States)

    Frade, R; Barel, M; Ehlin-Henriksson, B; Klein, G

    1985-03-01

    The relationship between gp140, the membrane C3d receptor (CR2) of human B lymphocytes, and the Epstein-Barr virus receptor (EBVR) was analyzed by using the polyclonal anti-gp140, previously prepared by immunizing rabbits with highly purified gp140 (isolated by some of us) from CR2/EBVR-positive Raji cells. Polyclonal anti-gp72, a C3-binding membrane component, not related to the EBVR but also expressed on the Raji cell surface, was used as a control. Binding of rabbit IgG and EBV on cells was assessed by using immunofluorescence techniques with analysis by flow cytofluorometry. A semiquantitative bioassay was also used to measure the EBV binding. Polyclonal monospecific anti-gp140 IgG inhibits directly the binding of EBV to Raji cells at the same concentration that inhibits the binding of EC3d on cells, whereas a 35 times higher concentration of anti-gp72 IgG or preimmune serum IgG does not. Anti-gp140 IgG treatment also inhibits the induction of EBV-determined nuclear antigen in normal tonsil B lymphocytes or in EBV-negative Ramos cells, whereas high concentrations of anti-gp72 IgG or preimmune serum IgG have no effect. These data strongly suggest that gp140, the CR2 of human B lymphocytes, is also the EBVR. PMID:2983347

  9. Immunization of rabbits with highly purified, soluble, trimeric human immunodeficiency virus type 1 envelope glycoprotein induces a vigorous B cell response and broadly cross-reactive neutralization.

    Directory of Open Access Journals (Sweden)

    Gerald V Quinnan

    Full Text Available Previously we described induction of cross-reactive HIV-1 neutralizing antibody responses in rabbits using a soluble HIV-1 gp140 envelope glycoprotein (Env in an adjuvant containing monophosphoryl lipid A (MPL and QS21 (AS02A. Here, we compared different forms of the same HIV-1 strain R2 Env for antigenic and biophysical characteristics, and in rabbits characterized the extent of B cell induction for specific antibody expression and secretion and neutralizing responses. The forms of this Env that were produced in and purified from stably transformed 293T cells included a primarily dimeric gp140, a trimeric gp140 appended to a GCN4 trimerization domain (gp140-GCN4, gp140-GCN4 with a 15 amino acid flexible linker between the gp120 and gp41 ectodomain (gp140-GCN4-L, also trimeric, and a gp140 with the flexible linker purified from cell culture supernatants as either dimer (gp140-L(D or monomer (gp140-L(M. Multimeric states of the Env proteins were assessed by native gel electrophoresis and analytical ultracentrifugation. The different forms of gp140 bound broadly cross-reactive neutralizing (BCN human monoclonal antibodies (mAbs similarly in ELISA and immunoprecipitation assays. All Envs bound CD4i mAbs in the presence and absence of sCD4, as reported for the R2 Env. Weak neutralization of some strains of HIV-1 was seen after two additional doses in AS02A. Rabbits that were given a seventh dose of gp140-GCN4-L developed BCN responses that were weak to moderate, similar to our previous report. The specificity of these responses did not appear similar to that of any of the known BCN human mAbs. Induction of spleen B cell and plasma cells producing immunoglobulins that bound trimeric gp140-GCN4-L was vigorous, based on ELISpot and flow cytometry analyses. The results demonstrate that highly purified gp140-GCN4-L trimer in adjuvant elicits BCN responses in rabbits accompanied by vigorous B cell induction.

  10. Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen

    OpenAIRE

    Arias, M. A.; Loxley, A; Eatmon, C; Van Roey, G; Fairhurst, D; Mitchnick, M; Dash, Philip; Cole, T.; Wegmann, F; Sattentau, Q; Shattock, R

    2011-01-01

    Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intra...

  11. Evaluation of TLR agonists as potential mucosal adjuvants for HIV gp140 and tetanus toxoid in mice.

    Directory of Open Access Journals (Sweden)

    Viviana Buffa

    Full Text Available In the present study we investigate the impact of a range of TLR ligands and chitosan as potential adjuvants for different routes of mucosal immunisation (sublingual (SL, intranasal (IN, intravaginal (IVag and a parenteral route (subcutaneous (SC in the murine model. We assess their ability to enhance antibody responses to HIV-1 CN54gp140 (gp140 and Tetanus toxoid (TT in systemic and vaginal compartments. A number of trends were observed by route of administration. For non-adjuvanted antigen, SC>SL>IN immunisation with respect to systemic IgG responses, where endpoint titres were greater for TT than for gp140. In general, co-administration with adjuvants increased specific IgG responses where IN = SC>SL, while in the vaginal compartment IN>SL>SC for specific IgA. In contrast, for systemic and mucosal IgA responses to antigen alone SL>IN = SC. A number of adjuvants increased specific systemic IgA responses where in general IN>SL>SC immunisation, while for mucosal responses IN = SL>SC. In contrast, direct intravaginal immunisation failed to induce any detectable systemic or mucosal responses to gp140 even in the presence of adjuvant. However, significant systemic IgG responses to TT were induced by intravaginal immunisation with or without adjuvant, and detectable mucosal responses IgG and IgA were observed when TT was administered with FSL-1 or Poly I∶C. Interestingly some TLRs displayed differential activity dependent upon the route of administration. MPLA (TLR4 suppressed systemic responses to SL immunisation while enhancing responses to IN or SC immunisation. CpG B enhanced SL and IN responses, while having little or no impact on SC immunisation. These data demonstrate important route, antigen and adjuvant effects that need to be considered in the design of mucosal vaccine strategies.

  12. Comparative evaluation of trimeric envelope glycoproteins derived from subtype C and B HIV-1 R5 isolates

    International Nuclear Information System (INIS)

    We previously reported that an envelope (Env) glycoprotein immunogen (o-gp140ΔV2SF162) containing a partial deletion in the second variable loop (V2) derived from the R5-tropic HIV-1 isolate SF162 partially protected vaccinated rhesus macaques against pathogenic SHIVSF162P4 virus. Extending our studies to subtype C isolate TV1, we have purified o-gp140ΔV2TV1 (subtype C ΔV2 trimer) to homogeneity, performed glycosylation analysis, and determined its ability to bind CD4, as well as a panel of well-characterized neutralizing monoclonal antibodies (mAb). In general, critical epitopes are preserved on the subtype C ΔV2 trimer; however, we did not observe significant binding for the b12 mAb. The molecular mass of subtype C ΔV2 trimer was found to be 450 kDa, and the hydrodynamic radius was found to be 10.87 nm. Our data suggest that subtype C ΔV2 trimer binds to CD4 with an affinity comparable to o-gp140ΔV2SF162 (subtype B ΔV2 trimer). Using isothermal titration calorimetric (ITC) analysis, we demonstrated that all three CD4 binding sites (CD4-BS) in both subtype C and B trimers are exposed and accessible. However, compared to subtype B trimer, the three CD4-BS in subtype C trimer have different affinities for CD4, suggesting a cooperativity of CD4 binding in subtype C trimer but not in subtype B trimer. Negative staining electron microscopy of the subtype C ΔV2 trimer has demonstrated that it is in fact a trimer. These results highlight the importance of studying subtype C Env, and also of developing appropriate subtype C-specific reagents that may be used for better immunological characterization of subtype C Env for developing an AIDS vaccine

  13. Targeting HIV-1 Envelope Glycoprotein Trimers to B Cells by Using APRIL Improves Antibody Responses

    OpenAIRE

    Melchers M; Bontjer I; Tong T; Chung NP; Klasse PJ; Eggink D; Montefiori DC; Gentile M; Cerutti A; Olson WC; Berkhout B; Binley JM; Moore JP; Sanders RW

    2012-01-01

    An HIV-1 vaccine remains elusive, in part because various factors limit the quantity and quality of the antibodies raised against the viral envelope glycoprotein complex (Env). We hypothesized that targeting Env vaccines directly to B cells, by fusing them to molecules that bind and activate these cells, would improve Env-specific antibody responses. Therefore, we fused trimeric Env gp140 to A PRoliferation-Inducing Ligand (APRIL), B-cell Activating Factor (BAFF), and CD40 Ligand (CD40L). The...

  14. Salmonella typhi Ty21a bacterial ghost vector augments HIV-1 gp140 DNA vaccine-induced peripheral and mucosal antibody responses via TLR4 pathway.

    Science.gov (United States)

    Wen, Jing; Yang, Yi; Zhao, Guangyu; Tong, Shuang; Yu, Hong; Jin, Xia; Du, Lanying; Jiang, Shibo; Kou, Zhihua; Zhou, Yusen

    2012-08-24

    Because of their stability and ease of manipulation, DNA vaccines have considerable potential for eliciting immune responses. However, they are limited by their weak immunogenicity, especially in humans. To address this challenge, we explored a new strategy of HIV vaccine delivery using Salmonella typhi Ty21a bacterial ghosts (BGs). We found that Ty21a BGs loaded with an HIV gp140 DNA vaccine (Ty21a BG-DNA) were readily taken up by murine macrophage RAW264.7 cells, and gp140 was efficiently expressed in these cells. Peripheral and intestinal mucosal anti-gp120 antibody responses in mice vaccinated with BGs-DNA vaccine were significantly higher than those in mice immunized with naked DNA vaccine. The enhancement of antibody responses was associated with BG-induced production of IL-10 through TLR4 pathway. These results demonstrate that Ty21a BGs is a novel and effective delivery vehicle for DNA vaccines, which could therefore be used as a new strategy for development of HIV vaccines. PMID:22819719

  15. gp140v-fms molecules expressed at the surface of cells transformed by the McDonough strain of feline sarcoma virus are phosphorylated in tyrosine and serine.

    OpenAIRE

    Tamura, T.; Simon, E.; Niemann, H.; Snoek, G T; Bauer, H.

    1986-01-01

    Cells transformed by the McDonough strain of feline sarcoma virus express at their surface a v-fms-specific transmembrane glycoprotein designated gp140v-fms. By labeling with 32Pi, gp140v-fms was shown to be phosphorylated 30-fold more in serine residues than were the cytosolic v-fms polypeptides gp180gag-fms and gp120v-fms. By using the phosphotyrosine phosphatase-specific inhibitor sodium orthovanadate, an additional tyrosine phosphorylation was observed in vivo, again involving predominant...

  16. Subtype C gp140 Vaccine Boosts Immune Responses Primed by the South African AIDS Vaccine Initiative DNA-C2 and MVA-C HIV Vaccines after More than a 2-Year Gap.

    Science.gov (United States)

    Gray, Glenda E; Mayer, Kenneth H; Elizaga, Marnie L; Bekker, Linda-Gail; Allen, Mary; Morris, Lynn; Montefiori, David; De Rosa, Stephen C; Sato, Alicia; Gu, Niya; Tomaras, Georgia D; Tucker, Timothy; Barnett, Susan W; Mkhize, Nonhlanhla N; Shen, Xiaoying; Downing, Katrina; Williamson, Carolyn; Pensiero, Michael; Corey, Lawrence; Williamson, Anna-Lise

    2016-06-01

    A phase I safety and immunogenicity study investigated South African AIDS Vaccine Initiative (SAAVI) HIV-1 subtype C (HIV-1C) DNA vaccine encoding Gag-RT-Tat-Nef and gp150, boosted with modified vaccinia Ankara (MVA) expressing matched antigens. Following the finding of partial protective efficacy in the RV144 HIV vaccine efficacy trial, a protein boost with HIV-1 subtype C V2-deleted gp140 with MF59 was added to the regimen. A total of 48 participants (12 U.S. participants and 36 Republic of South Africa [RSA] participants) were randomized to receive 3 intramuscular (i.m.) doses of SAAVI DNA-C2 of 4 mg (months 0, 1, and 2) and 2 i.m. doses of SAAVI MVA-C of 1.45 × 10(9) PFU (months 4 and 5) (n = 40) or of a placebo (n = 8). Approximately 2 years after vaccination, 27 participants were rerandomized to receive gp140/MF59 at 100 μg or placebo, as 2 i.m. injections, 3 months apart. The vaccine regimen was safe and well tolerated. After the DNA-MVA regimen, CD4(+) T-cell and CD8(+) T-cell responses occurred in 74% and 32% of the participants, respectively. The protein boost increased CD4(+) T-cell responses to 87% of the subjects. All participants developed tier 1 HIV-1C neutralizing antibody responses as well as durable Env binding antibodies that recognized linear V3 and C5 peptides. The HIV-1 subtype C DNA-MVA vaccine regimen showed promising cellular immunogenicity. Boosting with gp140/MF59 enhanced levels of binding and neutralizing antibodies as well as CD4(+) T-cell responses to HIV-1 envelope. (This study has been registered at ClinicalTrials.gov under registration no. NCT00574600 and NCT01423825.). PMID:27098021

  17. Comparing the Effects of Symbiotic Algae (Symbiodinium) Clades C1 and D on Early Growth Stages of Acropora tenuis

    OpenAIRE

    Yuyama, Ikuko; Higuchi, Tomihiko

    2014-01-01

    Reef-building corals switch endosymbiotic algae of the genus Symbiodinium during their early growth stages and during bleaching events. Clade C Symbiodinium algae are dominant in corals, although other clades — including A and D — have also been commonly detected in juvenile Acroporid corals. Previous studies have been reported that only molecular data of Symbiodinium clade were identified within field corals. In this study, we inoculated aposymbiotic juvenile polyps with cultures of clades C...

  18. HIV-1 specific IgA detected in vaginal secretions of HIV uninfected women participating in a microbicide trial in Southern Africa are primarily directed toward gp120 and gp140 specificities.

    Directory of Open Access Journals (Sweden)

    Kelly E Seaton

    Full Text Available BACKGROUND: Many participants in microbicide trials remain uninfected despite ongoing exposure to HIV-1. Determining the emergence and nature of mucosal HIV-specific immune responses in such women is important, since these responses may contribute to protection and could provide insight for the rational design of HIV-1 vaccines. METHODS AND FINDINGS: We first conducted a pilot study to compare three sampling devices (Dacron swabs, flocked nylon swabs and Merocel sponges for detection of HIV-1-specific IgG and IgA antibodies in vaginal secretions. IgG antibodies from HIV-1-positive women reacted broadly across the full panel of eight HIV-1 envelope (Env antigens tested, whereas IgA antibodies only reacted to the gp41 subunit. No Env-reactive antibodies were detected in the HIV-negative women. The three sampling devices yielded equal HIV-1-specific antibody titers, as well as total IgG and IgA concentrations. We then tested vaginal Dacron swabs archived from 57 HIV seronegative women who participated in a microbicide efficacy trial in Southern Africa (HPTN 035. We detected vaginal IgA antibodies directed at HIV-1 Env gp120/gp140 in six of these women, and at gp41 in another three women, but did not detect Env-specific IgG antibodies in any women. CONCLUSION: Vaginal secretions of HIV-1 infected women contained IgG reactivity to a broad range of Env antigens and IgA reactivity to gp41. In contrast, Env-binding antibodies in the vaginal secretions of HIV-1 uninfected women participating in the microbicide trial were restricted to the IgA subtype and were mostly directed at HIV-1 gp120/gp140.

  19. Comparing the effects of symbiotic algae (Symbiodinium clades C1 and D on early growth stages of Acropora tenuis.

    Directory of Open Access Journals (Sweden)

    Ikuko Yuyama

    Full Text Available Reef-building corals switch endosymbiotic algae of the genus Symbiodinium during their early growth stages and during bleaching events. Clade C Symbiodinium algae are dominant in corals, although other clades - including A and D - have also been commonly detected in juvenile Acroporid corals. Previous studies have been reported that only molecular data of Symbiodinium clade were identified within field corals. In this study, we inoculated aposymbiotic juvenile polyps with cultures of clades C1 and D Symbiodinium algae, and investigated the different effect of these two clades of Symbiodinium on juvenile polyps. Our results showed that clade C1 algae did not grow, while clade D algae grew rapidly during the first 2 months after inoculation. Polyps associated with clade C1 algae exhibited bright green fluorescence across the body and tentacles after inoculation. The growth rate of polyp skeletons was lower in polyps associated with clade C1 algae than those associated with clade D algae. On the other hand, antioxidant activity (catalase of corals was not significantly different between corals with clade C1 and clade D algae. Our results suggested that clade D Symbiodinium algae easily form symbiotic relationships with corals and that these algae could contribute to coral growth in early symbiosis stages.

  20. The chloroplast genome of a symbiodinium sp. clade C3 isolate

    KAUST Repository

    Barbrook, Adrian C.

    2014-01-01

    Dinoflagellate algae of the genus Symbiodinium form important symbioses within corals and other benthic marine animals. Dinoflagellates possess an extremely reduced plastid genome relative to those examined in plants and other algae. In dinoflagellates the plastid genes are located on small plasmids, commonly referred to as \\'minicircles\\'. However, the chloroplast genomes of dinoflagellates have only been extensively characterised from a handful of species. There is also evidence of considerable variation in the chloroplast genome organisation across those species that have been examined. We therefore characterised the chloroplast genome from an environmental coral isolate, in this case containing a symbiont belonging to the Symbiodinium sp. clade C3. The gene content of the genome is well conserved with respect to previously characterised genomes. However, unlike previously characterised dinoflagellate chloroplast genomes we did not identify any \\'empty\\' minicircles. The sequences of this chloroplast genome show a high rate of evolution relative to other algal species. Particularly notable was a surprisingly high level of sequence divergence within the core polypeptides of photosystem I, the reasons for which are currently unknown. This chloroplast genome also possesses distinctive codon usage and GC content. These features suggest that chloroplast genomes in Symbiodinium are highly plastic. © 2013 Adrian C. Barbrook.

  1. Synergistic activity profile of griffithsin in combination with tenofovir, maraviroc and enfuvirtide against HIV-1 clade C

    International Nuclear Information System (INIS)

    Griffithsin (GRFT) is possibly the most potent anti-HIV peptide found in natural sources. Due to its potent and broad-spectrum antiviral activity and unique safety profile it has great potential as topical microbicide component. Here, we evaluated various combinations of GRFT against HIV-1 clade B and clade C isolates in primary peripheral blood mononuclear cells (PBMCs) and in CD4+ MT-4 cells. In all combinations tested, GRFT showed synergistic activity profile with tenofovir, maraviroc and enfuvirtide based on the median effect principle with combination indices (CI) varying between 0.34 and 0.79 at the calculated EC95 level. Furthermore, the different glycosylation patterns on the viral envelope of clade B and clade C gp120 had no observable effect on the synergistic interactions. Overall, we can conclude that the evaluated two-drug combination increases their antiviral potency and supports further clinical investigations in pre-exposure prophylaxis for GRFT combinations in the context of HIV-1 clade C infection.

  2. SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env cause AIDS in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Siddappa Nagadenahalli B

    2008-10-01

    Full Text Available Abstract Background Infection of nonhuman primates with simian immunodeficiency virus (SIV or chimeric simian-human immunodeficiency virus (SHIV strains is widely used to study lentiviral pathogenesis, antiviral immunity and the efficacy of AIDS vaccine candidates. SHIV challenges allow assessment of anti-HIV-1 envelope responses in primates. As such, SHIVs should mimic natural HIV-1 infection in humans and, to address the pandemic, encode HIV-1 Env components representing major viral subtypes worldwide. Results We have developed a panel of clade C R5-tropic SHIVs based upon env of a Zambian pediatric isolate of HIV-1 clade C, the world's most prevalent HIV-1 subtype. The parental infectious proviral clone, SHIV-1157i, was rapidly passaged through five rhesus monkeys. After AIDS developed in the first animal at week 123 post-inoculation, infected blood was infused into a sixth monkey. Virus reisolated at this late stage was still exclusively R5 tropic and mucosally transmissible. Here we describe the long-term follow-up of this initial cohort of six monkeys. Two have remained non-progressors, whereas the other four gradually progressed to AIDS within 123–270 weeks post-exposure. Two progressors succumbed to opportunistic infections, including a case of SV40 encephalitis. Conclusion These data document the disease progression induced by the first mucosally transmissible, pathogenic R5 non-clade B SHIV and suggest that SHIV-1157i-derived viruses, including the late-stage, highly replication-competent SHIV-1157ipd3N4 previously described (Song et al., 2006, display biological characteristics that mirror those of HIV-1 clade C and support their expanded use for AIDS vaccine studies in nonhuman primates.

  3. A novel strategy for efficient production of anti-V3 human scFvs against HIV-1 clade C

    Directory of Open Access Journals (Sweden)

    Kumar Rajesh

    2012-11-01

    Full Text Available Abstract Background Production of human monoclonal antibodies that exhibit broadly neutralizing activity is needed for preventing HIV-1 infection, however only a few such antibodies have been generated till date. Isolation of antibodies by the hybridoma technology is a cumbersome process with fewer yields. Further, the loss of unstable or slowly growing clones which may have unique binding specificities often occurs during cloning and propagation and the strongly positive clones are often lost. This has been avoided by the process described in this paper, wherein, by combining the strategy of EBV transformation and recombinant DNA technology, we constructed human single chain variable fragments (scFvs against the third variable region (V3 of the clade C HIV-1 envelope. Results An antigen specific phage library of 7000 clones was constructed from the enriched V3- positive antibody secreting EBV transformed cells. By ligation of the digested scFv DNA into phagemid vector and bio panning against the HIV-1 consensus C and B V3 peptides followed by random selection of 40 clones, we identified 15 clones that showed V3 reactivity in phage ELISA. DNA fingerprinting analysis and sequencing showed that 13 out of the 15 clones were distinct. Expression of the positive clones was tested by SDS-PAGE and Western blot. All the 13 anti-V3 scFvs showed cross-reactivity against both the clade C and B V3 peptides and did not show any reactivity against other unrelated peptides in ELISA. Preliminary neutralization assays indicated varying degrees of neutralization of clade C and B viruses. EBV transformation, followed by antigen selection of lines to identify specific binders, enabled the selection of phage from un-cloned lines for scFv generation, thus avoiding the problems of hybridoma technology. Moreover, as the clones were pretested for antigen binding, a comparatively small library sufficed for the selection of a considerable number of unique antigen binding

  4. Functional characterization of two scFv-Fc antibodies from an HIV controller selected on soluble HIV-1 Env complexes: a neutralizing V3- and a trimer-specific gp41 antibody.

    Directory of Open Access Journals (Sweden)

    Maria Trott

    Full Text Available HIV neutralizing antibodies (nAbs represent an important tool in view of prophylactic and therapeutic applications for HIV-1 infection. Patients chronically infected by HIV-1 represent a valuable source for nAbs. HIV controllers, including long-term non-progressors (LTNP and elite controllers (EC, represent an interesting subgroup in this regard, as here nAbs can develop over time in a rather healthy immune system and in the absence of any therapeutic selection pressure. In this study, we characterized two particular antibodies that were selected as scFv antibody fragments from a phage immune library generated from an LTNP with HIV neutralizing antibodies in his plasma. The phage library was screened on recombinant soluble gp140 envelope (Env proteins. Sequencing the selected peptide inserts revealed two major classes of antibody sequences. Binding analysis of the corresponding scFv-Fc derivatives to various trimeric and monomeric Env constructs as well as to peptide arrays showed that one class, represented by monoclonal antibody (mAb A2, specifically recognizes an epitope localized in the pocket binding domain of the C heptad repeat (CHR in the ectodomain of gp41, but only in the trimeric context. Thus, this antibody represents an interesting tool for trimer identification. MAb A7, representing the second class, binds to structural elements of the third variable loop V3 and neutralizes tier 1 and tier 2 HIV-1 isolates of different subtypes with matching critical amino acids in the linear epitope sequence. In conclusion, HIV controllers are a valuable source for the selection of functionally interesting antibodies that can be selected on soluble gp140 proteins with properties from the native envelope spike.

  5. HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms.

    Science.gov (United States)

    Deshpande, Suprit; Patil, Shilpa; Kumar, Rajesh; Hermanus, Tandile; Murugavel, Kailapuri G; Srikrishnan, Aylur K; Solomon, Suniti; Morris, Lynn; Bhattacharya, Jayanta

    2016-01-01

    The glycan supersite centered on N332 in the V3 base of the HIV-1 envelope (Env) is a target for broadly neutralizing antibodies (bnAbs) such as PGT121 and PGT128. In this study, we examined the basis of resistance of HIV-1 clade C Envs obtained from broadly cross neutralizing (BCN) plasma of an Indian donor with N332 specificity. Pseudotyped viruses expressing autologous envs were found to be resistant to autologous BCN plasma as well as to PGT121 and PGT128 mAbs despite the majority of Envs containing an intact N332 residue. While resistance of one of the Envs to neutralization by autologous plasma antibodies with shorter V1 loop length was found to be correlated with a N332S mutation, resistance to neutralization of rest of the Envs was found to be associated with longer V1 loop length and acquisition of protective N-glycans. In summary, we show evidence of escape of circulating HIV-1 clade C in an individual from autologous BCN antibodies by three distinct mechanisms. PMID:27576440

  6. Schistosoma mansoni enhances host susceptibility to mucosal but not intravenous challenge by R5 Clade C SHIV.

    Directory of Open Access Journals (Sweden)

    Nagadenahalli B Siddappa

    2011-08-01

    Full Text Available BACKGROUND: The high prevalence of HIV-1/AIDS in areas endemic for schistosomiasis and other helminthic infections has led to the hypothesis that parasites increase host susceptibility to immunodeficiency virus infection. We previously showed that rhesus macaques (RM with active schistosomiasis were significantly more likely to become systemically infected after intrarectal (i.r. exposure to an R5-tropic clade C simian-human immunodeficiency virus (SHIV-C than were parasite-free controls. However, we could not address whether this was due to systemic or mucosal effects. If systemic immunoactivation resulted in increased susceptibility to SHIV-C acquisition, a similarly large difference in host susceptibility would be seen after intravenous (i.v. SHIV-C challenge. Conversely, if increased host susceptibility was due to parasite-induced immunoactivation at the mucosal level, i.v. SHIV-C challenge would not result in significant differences between parasitized and parasite-free monkeys. METHODS AND FINDINGS: We enrolled two groups of RM and infected one group with Schistosoma mansoni; the other group was left parasite-free. Both groups were challenged i.v. with decreasing doses of SHIV-C. No statistically significant differences in 50% animal infectious doses (AID(50 or peak viremia were seen between the two groups. These data strongly contrast the earlier i.r. SHIV-C challenge (using the same virus stock in the presence/absence of parasites, where we noted a 17-fold difference in AID(50 and one log higher peak viremia in parasitized monkeys (P90% of all new HIV-1 infections worldwide are acquired through mucosal contact, parasitic infections that inflame mucosae may play an important role in the spread of HIV-1.

  7. Complete epitopes for vaccine design derived from a crystal structure of the broadly neutralizing antibodies PGT128 and 8ANC195 in complex with an HIV-1 Env trimer.

    Science.gov (United States)

    Kong, Leopold; Torrents de la Peña, Alba; Deller, Marc C; Garces, Fernando; Sliepen, Kwinten; Hua, Yuanzi; Stanfield, Robyn L; Sanders, Rogier W; Wilson, Ian A

    2015-10-01

    The HIV-1 envelope gp160 glycoprotein (Env) is a trimer of gp120 and gp41 heterodimers that mediates cell entry and is the primary target of the humoral immune response. Broadly neutralizing antibodies (bNAbs) to HIV-1 have revealed multiple epitopes or sites of vulnerability, but mapping of most of these sites is incomplete owing to a paucity of structural information on the full epitope in the context of the Env trimer. Here, a crystal structure of the soluble BG505 SOSIP gp140 trimer at 4.6 Å resolution with the bNAbs 8ANC195 and PGT128 reveals additional interactions in comparison to previous antibody-gp120 structures. For 8ANC195, in addition to previously documented interactions with gp120, a substantial interface with gp41 is now elucidated that includes extensive interactions with the N637 glycan. Surprisingly, removal of the N637 glycan did not impact 8ANC195 affinity, suggesting that the antibody has evolved to accommodate this glycan without loss of binding energy. PGT128 indirectly affects the N262 glycan by a domino effect, in which PGT128 binds to the N301 glycan, which in turn interacts with and repositions the N262 glycan, thereby illustrating the important role of neighboring glycans on epitope conformation and stability. Comparisons with other Env trimer and gp120 structures support an induced conformation for glycan N262, suggesting that the glycan shield is allosterically modified upon PGT128 binding. These complete epitopes of two broadly neutralizing antibodies on the Env trimer can now be exploited for HIV-1 vaccine design. PMID:26457433

  8. Old World and Clade C New World Arenaviruses Mimic the Molecular Mechanism of Receptor Recognition Used by α-Dystroglycan's Host-Derived Ligands▿

    OpenAIRE

    Rojek, Jillian M.; Spiropoulou, Christina F.; Campbell, Kevin P.; Kunz, Stefan

    2007-01-01

    α-Dystroglycan (DG) is an important cellular receptor for extracellular matrix (ECM) proteins and also serves as the receptor for Old World arenaviruses Lassa fever virus (LFV) and lymphocytic choriomeningitis virus (LCMV) and clade C New World arenaviruses. In the host cell, α-DG is subject to a remarkably complex pattern of O glycosylation that is crucial for its interactions with ECM proteins. Two of these unusual sugar modifications, protein O mannosylation and glycan modifications involv...

  9. Elusive structure of helium trimers

    CERN Document Server

    Stipanović, Petar; Boronat, Jordi

    2016-01-01

    Over the years many He-He interaction potentials have been developed, some very sophisticated, including various corrections beyond Born-Oppenheimer approximation. Most of them were used to predict properties of helium dimers and trimers, examples of exotic quantum states, whose experimental study proved to be very challenging. Recently, detailed structural properties of helium trimers were measured for the first time, allowing a comparison with theoretical predictions and possibly enabling the evaluation of different interaction potentials. The comparisons already made included adjusting the maxima of both theoretical and experimental correlation functions to one, so the overall agreement between theory and experiment appeared satisfactory. However, no attempt was made to evaluate the quality of the interaction potentials used in the calculations. In this work, we calculate the experimentally measured correlation functions using both new and old potentials, compare them with experimental data and rank the po...

  10. Fluorescence and Thermostability of Nanometer Porphyrin Trimer

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A nanometer porphyrin trimer was firstly synthesized with 1,3-dibromopropane as a bridge-linked agent and the fluorescence property and thermostability were studied. The results show that the fluorescence property and thermostability of the trimer are different from those of monoporphyrin. The effects of the molecule structure on the optical property and the thermostability were also studied in detail.

  11. R5 clade C SHIV strains with tier 1 or 2 neutralization sensitivity: tools to dissect env evolution and to develop AIDS vaccines in primate models.

    Directory of Open Access Journals (Sweden)

    Nagadenahalli B Siddappa

    Full Text Available BACKGROUND: HIV-1 clade C (HIV-C predominates worldwide, and anti-HIV-C vaccines are urgently needed. Neutralizing antibody (nAb responses are considered important but have proved difficult to elicit. Although some current immunogens elicit antibodies that neutralize highly neutralization-sensitive (tier 1 HIV strains, most circulating HIVs exhibiting a less sensitive (tier 2 phenotype are not neutralized. Thus, both tier 1 and 2 viruses are needed for vaccine discovery in nonhuman primate models. METHODOLOGY/PRINCIPAL FINDINGS: We constructed a tier 1 simian-human immunodeficiency virus, SHIV-1157ipEL, by inserting an "early," recently transmitted HIV-C env into the SHIV-1157ipd3N4 backbone [1] encoding a "late" form of the same env, which had evolved in a SHIV-infected rhesus monkey (RM with AIDS. SHIV-1157ipEL was rapidly passaged to yield SHIV-1157ipEL-p, which remained exclusively R5-tropic and had a tier 1 phenotype, in contrast to "late" SHIV-1157ipd3N4 (tier 2. After 5 weekly low-dose intrarectal exposures, SHIV-1157ipEL-p systemically infected 16 out of 17 RM with high peak viral RNA loads and depleted gut CD4+ T cells. SHIV-1157ipEL-p and SHIV-1157ipd3N4 env genes diverge mostly in V1/V2. Molecular modeling revealed a possible mechanism for the increased neutralization resistance of SHIV-1157ipd3N4 Env: V2 loops hindering access to the CD4 binding site, shown experimentally with nAb b12. Similar mutations have been linked to decreased neutralization sensitivity in HIV-C strains isolated from humans over time, indicating parallel HIV-C Env evolution in humans and RM. CONCLUSIONS/SIGNIFICANCE: SHIV-1157ipEL-p, the first tier 1 R5 clade C SHIV, and SHIV-1157ipd3N4, its tier 2 counterpart, represent biologically relevant tools for anti-HIV-C vaccine development in primates.

  12. Variations in the Biological Functions of HIV-1 Clade C Envelope in a SHIV-Infected Rhesus Macaque during Disease Progression.

    Directory of Open Access Journals (Sweden)

    For Yue Tso

    Full Text Available A better understanding of how the biological functions of the HIV-1 envelope (Env changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection of macaque with SHIV, expressing HIV-1 clade C Env V1-V5 region. By using this model, we examined the changes in biological functions of Env in the infected animal over the entire disease course. Our data showed an increase in the neutralization resistance phenotype over time and coincided with the decrease in the net charges of the V1-V5 region. Infection of PBMC with provirus expressing various Env clones, isolated from the infected animal over time, showed a surprisingly better replicative fitness for viruses expressing the Env from early time point. Biotinylation and ELISA data also indicated a decrease of cell-surface-associated Env and virion-associated gp120 content with disease progression. This decrease did not affect the CD4-binding capability of Env, but were positively correlated with the decrease of Env fusion ability. Interestingly, some of these changes in biological functions reverted to the pre-AIDS level during advance AIDS. These data suggested a dynamic relationship between the Env V1-V5 region with the host immune pressure. The observed changes of biological functions in this setting might reflect and predict those occurring during natural disease progression in human.

  13. Efficiency of Neutralizing Antibodies Targeting the CD4-Binding Site: Influence of Conformational Masking by the V2 Loop in R5-Tropic Clade C Simian-Human Immunodeficiency Virus▿

    OpenAIRE

    Watkins, Jennifer D.; Diaz-Rodriguez, Juan; Siddappa, Nagadenahalli B.; Corti, Davide; Ruprecht, Ruth M.

    2011-01-01

    In R5-tropic clade C simian-human immunodeficiency viruses (SHIV-Cs), we identified a 3-asparagine (3N) deletion mutation in the V2 loop stem of gp120 as the major determinant of neutralization escape of the anti-CD4-binding site (anti-CD4-bs) neutralizing monoclonal antibody (nMAb) b12. However, the more potent anti-CD4-bs nMAbs VRC01 and VRC03 were not sensitive to this mutation. Using isogenic tier 1 or tier 2 proviruses differing only in the 3N mutation, we showed that this mutation might...

  14. Toughening Modification of Unsaturated Polyester Resin Using HDI Trimer

    Institute of Scientific and Technical Information of China (English)

    DUAN Huajun; ZHANG Lianmeng; WANG Jun; YANG Xiaoli; WANG Xiang

    2009-01-01

    HDI trimer was firstly used to improve the mechanical properties of hydroxyl-ter-minated unsaturated polyester(UP).Mechanical properties measurements performed on the cured materials demonstrate a distinct improvement in intensity and toughness in the presence of HDI trimer and shows the change trends of increase and then decrease.The morphological analysis of the fracture surfaces shows that the micro-phase separated structures appear in modified UPR systems and changed from dendritric,dimple and to cystiform structures with the increase of HDI trimer content.The presence of the cystiform structures made the modified UPR systems present the best properties.

  15. Microscopic study of the He2-SF6 trimers

    CERN Document Server

    Barletta, P; Kievsky, A; Navarro, J; Polls, A

    2003-01-01

    The He2-SF6 trimers, in their different He isotopic combinations, are studied both in the framework of the correlated Jastrow approach and of the Correlated Hyperspherical Harmonics expansion method. The energetics and structure of the He-SF6 dimers are analyzed, and the existence of a characteristic rotational band in the excitation spectrum is discussed, as well as the isotopic differences. The binding energies and the spatial properties of the trimers, in their ground and lowest lying excited states, obtained by the Jastrow ansatz are in excellent agreement with the results of the converged CHH expansion. The introduction of the He-He correlation makes all trimers bound by largely suppressing the short range He-He repulsion. The structural properties of the trimers are qualitatively explained in terms of the shape of the interactions, Pauli principle and masses of the constituents.

  16. Porcine parvovirus removal using trimer and biased hexamer peptides

    OpenAIRE

    Heldt, Caryn L.; Gurgel, Patrick V.; Jaykus, Lee-Ann; Carbonell, Ruben G.

    2011-01-01

    Assuring the microbiological safety of biological therapeutics remains an important concern. Our group has recently reported small trimeric peptides that have the ability to bind and remove a model non-enveloped virus, porcine parvovirus (PPV), from complex solutions containing human blood plasma. In an effort to improve the removal efficiency of these small peptides, we created a biased library of hexamer peptides that contain two previously reported trimeric peptides designated WRW and KYY....

  17. Microscopic study of He-2-SF6 trimers

    OpenAIRE

    P. Barletta(University College London, UK); Fabrocini, A.; A. Kievsky(INFN, Pisa, Italy); Navarro Faus, Jesús; Polls, Artur

    2003-01-01

    The He2-SF6 trimers, in their different He isotopic combinations, are studied in the framework of both the correlated Jastrow approach and the correlated hyperspherical harmonics (CHH) expansion method. The energetics and structure of the He-SF6 dimers are analyzed, and the existence of a characteristic rotational band in the excitation spectrum is discussed, as well as the isotopic differences. The binding energies and the spatial properties of the trimers, in their ground and lowest lying e...

  18. Biosynthesis of fluorescent cyanobacterial allophycocyanin trimer in Escherichia coli.

    Science.gov (United States)

    Liu, Shaofang; Chen, Yingjie; Lu, Yandu; Chen, Huaxin; Li, Fuchao; Qin, Song

    2010-08-01

    Allophycocyanin (APC), a cyanobacterial photosynthetic phycobiliprotein, functions in energy transfer as a light-harvesting protein. One of the prominent spectroscopic characteristics of APC is a strong red-shift in the absorption and emission maxima when monomers are assembled into a trimer. Previously, holo-APC alpha and beta subunits (holo-ApcA and ApcB) were successfully synthesized in Escherichia coli. In this study, both holo-subunits from Synechocystis sp. PCC 6803 were co-expressed in E. coli, and found to self-assemble into trimers. The recombinant APC trimer was purified by metal affinity and size-exclusion chromatography, and had a native structure identical to native APC, as determined by characteristic spectroscopic measurements, fluorescence quantum yield, tryptic digestion analysis, and molecular weight measurements. Combined with results from a study in which only the monomer was formed, our results indicate that bilin synthesis and the subsequent attachment to apo-subunits are important for the successful assembly of APC trimers. This is the first study to report on the assembly of recombinant ApcA and ApcB into a trimer with native structure. Our study provides a promising method for producing better fluorescent tags, as well as a method to facilitate the genetic analysis of APC trimer assembly and biological function. PMID:20607408

  19. Predicted 3D Model of the Rabies Virus Glycoprotein Trimer

    Science.gov (United States)

    Fernando, Bastida-González; Yersin, Celaya-Trejo; José, Correa-Basurto; Paola, Zárate-Segura

    2016-01-01

    The RABVG ectodomain is a homotrimer, and trimers are often called spikes. They are responsible for the attachment of the virus through the interaction with nicotinic acetylcholine receptors, neural cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR). This makes them relevant in viral pathogenesis. The antigenic structure differs significantly between the trimers and monomers. Surfaces rich in hydrophobic amino acids are important for trimer stabilization in which the C-terminal of the ectodomain plays an important role; to understand these interactions between the G proteins, a mechanistic study of their functions was performed with a molecular model of G protein in its trimeric form. This verified its 3D conformation. The molecular modeling of G protein was performed by a I-TASSER server and was evaluated via a Rachamandran plot and ERRAT program obtained 84.64% and 89.9% of the residues in the favorable regions and overall quality factor, respectively. The molecular dynamics simulations were carried out on RABVG trimer at 310 K. From these theoretical studies, we retrieved the RMSD values from Cα atoms to assess stability. Preliminary model of G protein of rabies virus stable at 12 ns with molecular dynamics was obtained. PMID:27294109

  20. Properties of the molecular oxygen trimer from pairwise additive interactions

    International Nuclear Information System (INIS)

    Graphical abstract: The two lowest lying isomers of the molecular oxygen trimer. Diffusion Monte Carlo calculations indicate that the small potential barrier between them is surmountable when including zero-point energy. Highlights: ► Accurate calculation of the lowest isomers of the (O2)3 open-shell molecular trimer. ► Analysis of trimer structures in terms of dimer interactions. ► Analysis of vibrational ground state via accurate Diffusion Monte Carlo calculations. - Abstract: We report a theoretical study of the properties of the molecular oxygen trimer in its state of maximum spin multiplicity. The most stable structures for the complex were found using an accurate pair potential. Independent ab initio calculations on the trimer for selected geometries demonstrate the validity of this approximation and thus the small contribution of three-body effects. The three lowest structures found can be rationalized on the basis of the most stable dimer structures and possess C2, D3 and C2v point symmetries. The two lowest-lying structures are separated by only 0.6 meV and zero-point energy effects, which are sizable, reduce even further the gaps among the three structures studied. Diffusion Monte Carlo calculations indicate that the ground state vibrational wavefunction is mainly located around the C2 structure but also explores the D3 minimum, yielding a near oblate symmetric top with a binding energy of 32.1 meV.

  1. Tetranectin, a trimeric plasminogen-binding C-type lectin

    DEFF Research Database (Denmark)

    Holtet, T L; Graversen, Jonas Heilskov; Clemmensen, I;

    1997-01-01

    Tetranectin, a plasminogen-binding protein belonging to the family of C-type lectins, was expressed in E. coli and converted to its native form by in vitro refolding and proteolytic processing. Recombinant tetranectin-as well as natural tetranectin from human plasma-was shown by chemical cross......-linking analysis and SDS-PAGE to be a homo-trimer in solution as are other known members of the collectin family of C-type lectins. Biochemical evidence is presented showing that an N-terminal domain encoded within exons 1 and 2 of the tetranectin gene is necessary and sufficient to govern subunit trimerization....

  2. DNAzyme-Controlled Cleavage of Dimer and Trimer Origami Tiles.

    Science.gov (United States)

    Wu, Na; Willner, Itamar

    2016-04-13

    Dimers of origami tiles are bridged by the Pb(2+)-dependent DNAzyme sequence and its substrate or by the histidine-dependent DNAzyme sequence and its substrate to yield the dimers T1-T2 and T3-T4, respectively. The dimers are cleaved to monomer tiles in the presence of Pb(2+)-ions or histidine as triggers. Similarly, trimers of origami tiles are constructed by bridging the tiles with the Pb(2+)-ion-dependent DNAzyme sequence and the histidine-dependent DNAzyme sequence and their substrates yielding the trimer T1-T5-T4. In the presence of Pb(2+)-ions and/or histidine as triggers, the programmed cleavage of trimer proceeds. Using Pb(2+) or histidine as trigger cleaves the trimer to yield T5-T4 and T1 or the dimer T1-T5 and T4, respectively. In the presence of Pb(2+)-ions and histidine as triggers, the cleavage products are the monomer tiles T1, T5, and T4. The different cleavage products are identified by labeling the tiles with 0, 1, or 2 streptavidin labels and AFM imaging. PMID:26931508

  3. Rotation assisted diffusion of water trimers on Pd{111}

    Science.gov (United States)

    Ranea, Víctor A.; de Andres, P. L.

    2016-06-01

    Diffusion barriers for a cluster of three water molecules on Pd{111} have been estimated from ab-initio Density Functional Theory. A model for the diffusion of a cluster of three water molecules (trimer) based in rotations yields a simple explanation of why the cluster can diffuse faster than a single water molecule by a factor ≈ 102 [1]. This model is based on the differences between the adsorption geometry for the three molecules forming the trimer. One member interacts strongly with the surface and sits closer to the surface (d) while the other two interact weakly and stay at a larger separation from the surface (u). The trimer rotates nearly freely around the axis determined by the d-like monomer. Translations of the whole trimer imply breaking the strong interaction of the d-like molecule with the surface with a high energy cost. Alternatively, thermal fluctuations can exchange the position of the molecule sitting closer to the surface with a lower energetic cost. Rotations around different axis yield a diffusion mechanism where the strong interaction is maintained along the diffusion path, therefore lowering the effective activation barrier.

  4. Structure and Dynamics of the Native HIV-1 Env Trimer

    OpenAIRE

    Munro, James B.; Mothes, Walther

    2015-01-01

    HIV-1/AIDS remains one of the worst pandemics in human history. Despite tremendous efforts, no effective vaccine has been found. Recent reports give new insights into the structure and dynamics of the HIV-1 Env trimer and renew hopes that a better understanding of Env will translate into new vaccine candidates and more-effective antiretroviral therapies.

  5. Properties of the molecular oxygen trimer from pairwise additive interactions

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez-Lamoneda, Ramon, E-mail: ramon@uaem.mx [Centro de Investigaciones Quimicas, Universidad Autonoma del Estado de Morelos, 62210 Cuernavaca, Mor. (Mexico); Perez-Rios, Jesus; Carmona-Novillo, Estela; Bartolomei, Massimiliano; Campos-Martinez, Jose [Instituto de Fisica Fundamental, Consejo Superior de Investigaciones Cientificas (IFF-CSIC), Serrano 123, 28006 Madrid (Spain); Hernandez, Marta I., E-mail: marta@iff.csic.es [Instituto de Fisica Fundamental, Consejo Superior de Investigaciones Cientificas (IFF-CSIC), Serrano 123, 28006 Madrid (Spain)

    2012-05-03

    Graphical abstract: The two lowest lying isomers of the molecular oxygen trimer. Diffusion Monte Carlo calculations indicate that the small potential barrier between them is surmountable when including zero-point energy. Highlights: Black-Right-Pointing-Pointer Accurate calculation of the lowest isomers of the (O{sub 2}){sub 3} open-shell molecular trimer. Black-Right-Pointing-Pointer Analysis of trimer structures in terms of dimer interactions. Black-Right-Pointing-Pointer Analysis of vibrational ground state via accurate Diffusion Monte Carlo calculations. - Abstract: We report a theoretical study of the properties of the molecular oxygen trimer in its state of maximum spin multiplicity. The most stable structures for the complex were found using an accurate pair potential. Independent ab initio calculations on the trimer for selected geometries demonstrate the validity of this approximation and thus the small contribution of three-body effects. The three lowest structures found can be rationalized on the basis of the most stable dimer structures and possess C{sub 2}, D{sub 3} and C{sub 2v} point symmetries. The two lowest-lying structures are separated by only 0.6 meV and zero-point energy effects, which are sizable, reduce even further the gaps among the three structures studied. Diffusion Monte Carlo calculations indicate that the ground state vibrational wavefunction is mainly located around the C{sub 2} structure but also explores the D{sub 3} minimum, yielding a near oblate symmetric top with a binding energy of 32.1 meV.

  6. An anti-HIV-1 V3 loop antibody fully protects cross-clade and elicits T-cell immunity in macaques mucosally challenged with an R5 clade C SHIV.

    Directory of Open Access Journals (Sweden)

    Jennifer D Watkins

    Full Text Available Neutralizing antibodies have been shown to protect macaques against SHIV challenge. However, genetically diverse HIV-1 clades have evolved, and a key question left unanswered is whether neutralizing antibodies can confer cross-clade protection in vivo. The novel human monoclonal antibody HGN194 was isolated from an individual infected with an HIV-1 clade AG recombinant circulating recombinant form (CRF. HGN194 targets an epitope in the third hypervariable loop (V3 of HIV-1 gp120 and neutralizes a range of relatively neutralization-sensitive and resistant viruses. We evaluated the potential of HGN194 to protect infant rhesus monkeys against a SHIV encoding a primary CCR5-tropic HIV-1 clade C envelope. After high-dose mucosal challenge, all untreated controls became highly viremic while all HGN194-treated animals (50 mg/kg were completely protected. When HGN194 was given at 1 mg/kg, one out of two monkeys remained aviremic, whereas the other had delayed, lower peak viremia. Interestingly, all protected monkeys given high-dose HGN194 developed Gag-specific proliferative responses of both CD4+ and CD8+ T cells. To test whether generation of the latter involved cryptic infection, we ablated CD8+ cells after HGN194 clearance. No viremia was detected in any protected monkeys, thus ruling out virus reservoirs. Thus, induction of CD8 T-cell immunity may have resulted from transient "Hit and Run" infection or cross priming via Ag-Ab-mediated cross-presentation. Together, our data identified the HGN194 epitope as protective and provide proof-of-concept that this anti-V3 loop mAb can prevent infection with sterilizing immunity after challenge with virus of a different clade, implying that V3 is a potential vaccine target.

  7. Formation of unique trimer of nitric oxide on Cu(111)

    Energy Technology Data Exchange (ETDEWEB)

    Shiotari, A.; Hatta, S.; Okuyama, H., E-mail: hokuyama@kuchem.kyoto-u.ac.jp; Aruga, T. [Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan)

    2014-10-07

    We report that NO molecules unexpectedly prefer a trimeric configuration on Cu(111). We used scanning tunneling microscopy (STM) at 6 K, and confirmed that the NO molecule is bonded to the face-centered-cubic hollow site in an upright configuration. The individual NO molecule is imaged as a ring protrusion, which is characteristic of the doubly degenerate 2π{sup *} orbital. A triangular trimer is thermodynamically more favorable than the monomer and dimer, and its bonding structure was characterized by STM manipulation. This unique behavior of NO on Cu(111) is ascribed to the threefold symmetry of the surface, facilitating effective mixing of the 2π{sup *} orbitals in a triangular configuration.

  8. Interatomic Coulombic decay widths of helium trimer: Ab initio calculations

    Energy Technology Data Exchange (ETDEWEB)

    Kolorenč, Přemysl, E-mail: kolorenc@mbox.troja.mff.cuni.cz [Charles University in Prague, Faculty of Mathematics and Physics, Institute of Theoretical Physics, V Holešovičkách 2, 180 00 Prague (Czech Republic); Sisourat, Nicolas [Sorbonne Universités, UPMC Univ Paris 06, UMR 7614, Laboratoire de Chimie Physique Matière et Rayonnement, F-75005 Paris (France); CNRS, UMR 7614, Laboratoire de Chimie Physique Matière et Rayonnement, F-75005 Paris (France)

    2015-12-14

    We report on an extensive study of interatomic Coulombic decay (ICD) widths in helium trimer computed using a fully ab initio method based on the Fano theory of resonances. Algebraic diagrammatic construction for one-particle Green’s function is utilized for the solution of the many-electron problem. An advanced and universal approach to partitioning of the configuration space into discrete states and continuum subspaces is described and employed. Total decay widths are presented for all ICD-active states of the trimer characterized by one-site ionization and additional excitation of an electron into the second shell. Selected partial decay widths are analyzed in detail, showing how three-body effects can qualitatively change the character of certain relaxation transitions. Previously unreported type of three-electron decay processes is identified in one class of the metastable states.

  9. Dynamics of water trimer in femtosecond laser pulses

    Science.gov (United States)

    Wang, Zhiping; Zhang, Fengshou; Xu, Xuefeng; Wang, Yanbiao; Qian, Chaoyi

    2016-07-01

    With the help of the time-dependent local-density approximation (TDLDA) coupled non-adiabatically to molecular dynamics (MD), we studied both the static properties and irradiation dynamics of water trimer subject to the short and intense femtosecond laser field. It is shown that the optimized geometry and the optical absorption strength of the water trimer accord well with results in literature. Three typical possible irradiated scenarios of water trimer which are “normal oscillation”, “dissociation and formation” and “pure OH dissociation” are exhibited by investigating the ionization and the level depletion related to electrons as well as the OH bonds, proton-transfer, the intermolecular distance and the kinetic energy connected with ions. In three scenarios, the behaviors of water trimer can be attributed to the sequential combination of responses of the electrons emission, the proton-transfer, OH vibration and rotation, OH dissociation and hydroxyl formation, respectively. The relevant time scales of the first proton-transfer and OH dissociation are identified as 13 fs and 10-20 fs, respectively. The study of kinetic energies of ions show that the kinetic energies of the remaining ions are all below 4.5 eV and outgoing hydrogen ions carry a kinetic energy about 5-12 eV. Furthermore, it is found that in the tunneling ionization situations the depletion is fairly shared between the various levels except the most deep occupied electronic level while in the multiphotonic ionization case the electron loss comes from all single-electron levels and the HOMO level contributes the most.

  10. A randomised, placebo-controlled, first-in-human study of a novel clade C therapeutic peptide vaccine administered ex vivo to autologous white blood cells in HIV infected individuals.

    Directory of Open Access Journals (Sweden)

    Akil Jackson

    Full Text Available BACKGROUND: Preclinical studies of overlapping 15mer peptides, spanning SIV, SHIV or HIV, pulsed on autologous PBMC ex vivo have demonstrated high level, virus-specific T cell responses and viral suppression in non-human primates (NHP. Opal-HIV-Gag(c consists of 120 synthetic 15mer peptides spanning Clade C, consensus Gag, manufactured to current good manufacturing practice; having been evaluated in a good laboratory practice toxicology study in Macaca mulatta. We evaluated the safety and preliminary immunogenicity of such peptides administered intravenously after short-duration ex vivo incubation, to HIV-positive adults on suppressive antiretroviral therapy. METHODS AND FINDINGS: A first-in-human, placebo-controlled, double-blind, dose escalation study was conducted. Twenty-three patients with virus suppressed by antiretroviral therapy were enrolled in four groups 12 mg (n = 6, 24 mg (n = 6, 48 mg (n = 2 or matching placebo (n = 8. Treatment was administered intravenously after bedside enrichment of 120 mL whole blood for white cells using a closed system (Sepax S-100 device, with ex vivo peptide admixture (or diluent alone and 37°C incubation for one hour prior to reinfusion. Patients received 4 administrations at monthly intervals followed by a 12-week observation post-treatment. Opal-HIV-Gag(c was reasonably tolerated at doses of 12 and 24 mg. There was an increased incidence of temporally associated pyrexia, chills, and transient/self-limiting lymphopenia in Opal-HIV-Gag(c recipients compared to placebo. The study was terminated early, after two patients were recruited to the 48 mg cohort; a serious adverse event of hypotension, tachycardia secondary to diarrhoea occurred following a single product administration. An infectious cause for the event could not be identified, leaving the possibility of immunologically mediated product reaction. CONCLUSIONS: A serious, potentially life-threatening event of hypotension led to

  11. Hybridization and the origin of Fano resonances in symmetric nanoparticle trimers

    Science.gov (United States)

    Hopkins, Ben; Filonov, Dmitry S.; Glybovski, Stanislav B.; Miroshnichenko, Andrey E.

    2015-07-01

    We study the light scattering by plasmonic and dielectric symmetric trimers to investigate the existence of polarization-independent Fano resonances. Plasmonic hybridization theory is revealed to hide simple physics, and we instead provide a simplified model for hybridization to derive a plasmonic trimer's eigenmodes analytically. This approach is demonstrated to accurately recreate full wave simulations of plasmonic trimers and their Fano resonances. We are subsequently able to deduce the grounds for modal interference in plasmonic trimers and the related formation of Fano resonances. However, by generalizing our simplified hybridization approach, we are also able to investigate the eigenmodes of all-dielectric trimers. We show that bianisotropic coupling channels between high-index dielectric nanoparticles are able to increase the capacity for Fano resonances, even at normal incidence. We finally provide the first experimental measurements of sharp, polarization-independent Fano resonances from a symmetric all-dielectric trimer, with very good agreement with the predicted response from our simplified hybridization theory.

  12. Direct visualization of the trimeric structure of the ASIC1a channel, using AFM imaging.

    Science.gov (United States)

    Carnally, Stewart M; Dev, Harveer S; Stewart, Andrew P; Barrera, Nelson P; Van Bemmelen, Miguel X; Schild, Laurent; Henderson, Robert M; Edwardson, J Michael

    2008-08-01

    There has been confusion about the subunit stoichiometry of the degenerin family of ion channels. Recently, a crystal structure of acid-sensing ion channel (ASIC) 1a revealed that it assembles as a trimer. Here, we used atomic force microscopy (AFM) to image unprocessed ASIC1a bound to mica. We detected a mixture of subunit monomers, dimers and trimers. In some cases, triple-subunit clusters were clearly visible, confirming the trimeric structure of the channel, and indicating that the trimer sometimes disaggregated after adhesion to the mica surface. This AFM-based technique will now enable us to determine the subunit arrangement within heteromeric ASICs. PMID:18514062

  13. Direct visualization of the trimeric structure of the ASIC1a channel, using AFM imaging

    International Nuclear Information System (INIS)

    There has been confusion about the subunit stoichiometry of the degenerin family of ion channels. Recently, a crystal structure of acid-sensing ion channel (ASIC) 1a revealed that it assembles as a trimer. Here, we used atomic force microscopy (AFM) to image unprocessed ASIC1a bound to mica. We detected a mixture of subunit monomers, dimers and trimers. In some cases, triple-subunit clusters were clearly visible, confirming the trimeric structure of the channel, and indicating that the trimer sometimes disaggregated after adhesion to the mica surface. This AFM-based technique will now enable us to determine the subunit arrangement within heteromeric ASICs

  14. Resveratrol Trimers from Seed Cake of Paeonia rockii

    Directory of Open Access Journals (Sweden)

    Pu Liu

    2014-11-01

    Full Text Available In the course of screening natural products for antibacterial activities, a total acetone extract of the seed cake of Paeonia rockii showed significant effects against bacterial strains. Bioactivity-guided fractionation of the EtOAc-soluble fraction of the total acetone extract resulted in the isolation and identification of five resveratrol trimers, including rockiiol C (1, gnetin H (2, suffruticosol A (3, suffruticosol B (4 and suffruticosol C (5. The relative configuration of these compounds was elucidated mainly by comprehensive 1D and 2D-NMR experiments. Compound 1 was a new compound. All isolated compounds exhibited strong antibacterial activities against Gram-positive bacteria.

  15. Accurate calculations of bound rovibrational states for argon trimer

    Energy Technology Data Exchange (ETDEWEB)

    Brandon, Drew; Poirier, Bill [Department of Chemistry and Biochemistry, and Department of Physics, Texas Tech University, Box 41061, Lubbock, Texas 79409-1061 (United States)

    2014-07-21

    This work presents a comprehensive quantum dynamics calculation of the bound rovibrational eigenstates of argon trimer (Ar{sub 3}), using the ScalIT suite of parallel codes. The Ar{sub 3} rovibrational energy levels are computed to a very high level of accuracy (10{sup −3} cm{sup −1} or better), and up to the highest rotational and vibrational excitations for which bound states exist. For many of these rovibrational states, wavefunctions are also computed. Rare gas clusters such as Ar{sub 3} are interesting because the interatomic interactions manifest through long-range van der Waals forces, rather than through covalent chemical bonding. As a consequence, they exhibit strong Coriolis coupling between the rotational and vibrational degrees of freedom, as well as highly delocalized states, all of which renders accurate quantum dynamical calculation difficult. Moreover, with its (comparatively) deep potential well and heavy masses, Ar{sub 3} is an especially challenging rare gas trimer case. There are a great many rovibrational eigenstates to compute, and a very high density of states. Consequently, very few previous rovibrational state calculations for Ar{sub 3} may be found in the current literature—and only for the lowest-lying rotational excitations.

  16. Accurate calculations of bound rovibrational states for argon trimer

    International Nuclear Information System (INIS)

    This work presents a comprehensive quantum dynamics calculation of the bound rovibrational eigenstates of argon trimer (Ar3), using the ScalIT suite of parallel codes. The Ar3 rovibrational energy levels are computed to a very high level of accuracy (10−3 cm−1 or better), and up to the highest rotational and vibrational excitations for which bound states exist. For many of these rovibrational states, wavefunctions are also computed. Rare gas clusters such as Ar3 are interesting because the interatomic interactions manifest through long-range van der Waals forces, rather than through covalent chemical bonding. As a consequence, they exhibit strong Coriolis coupling between the rotational and vibrational degrees of freedom, as well as highly delocalized states, all of which renders accurate quantum dynamical calculation difficult. Moreover, with its (comparatively) deep potential well and heavy masses, Ar3 is an especially challenging rare gas trimer case. There are a great many rovibrational eigenstates to compute, and a very high density of states. Consequently, very few previous rovibrational state calculations for Ar3 may be found in the current literature—and only for the lowest-lying rotational excitations

  17. Antiviral properties of two trimeric recombinant gp41 proteins

    Directory of Open Access Journals (Sweden)

    Nisole Sébastien

    2006-03-01

    Full Text Available Abstract Background As it is the very first step of the HIV replication cycle, HIV entry represents an attractive target for the development of new antiviral drugs. In this context, fusion inhibitors are the third class of anti-HIV drugs to be used for treatment, in combination with nucleoside analogues and antiproteases. But the precise mechanism of HIV fusion mechanism is still unclear. Gp41 ectodomain-derived synthetic peptides represent ideal tools for clarifying this mechanism, in order to design more potent anti-HIV drugs. Results Two soluble trimeric recombinant gp41 proteins, termed Rgp41B and Rgp41A were designed. Both comprise the N- and C-terminal heptad repeat regions of the ectodomain of HIV-1 gp41, connected by a 7-residue hydrophilic linker, in order to mimic the trimeric fusogenic state of the transmembrane glycoprotein. Both recombinant proteins were found to inhibit HIV-1 entry into target cells in a dose-dependent manner. Rgp41A, the most potent inhibitor, was able to inhibit both X4 and R5 isolates into HeLa cells and primary T lymphocytes. X4 viruses were found to be more susceptible than R5 isolates to inhibition by Rgp41A. In order to elucidate how the trimeric recombinant gp41 protein can interfere with HIV-1 entry into target cells, we further investigated its mode of action. Rgp41A was able to bind gp120 but did not induce gp120-gp41 dissociation. Furthermore, this inhibitor could also interfere with a late step of the fusion process, following the mixing of lipids. Conclusion Taken together, our results suggest that Rgp41A can bind to gp120 and also interfere with a late event of the fusion process. Interestingly, Rgp41A can block membrane fusion without preventing lipid mixing. Although further work will be required to fully understand its mode of action, our results already suggest that Rgp41A can interfere with multiple steps of the HIV entry process.

  18. Understanding tantalum-catalyzed ethylene trimerization: When things go wrong

    KAUST Repository

    Chen, Yin

    2013-06-07

    Ethylene oligomerization to linear low-molecular-mass α-olefins is an open industrial challenge. Ta-based catalysts are promising systems, but the unclear understanding of their behavior prevents systematic advances in the field. We demonstrate here that a well-defined (î -SiO)3Ta III species is able to promote ethylene oligo-/polymerization without any cocatalyst, confirming that the active species in Ta systems corresponds to a TaIII species. DFT calculations on a series of Ta systems ranging from ethylene trimerization to ethylene polymerization catalysts highlight the key factors controlling their experimental behavior. Comparison of these Ta systems allows one to set general rules for the rational development of new ethylene Ta oligomerization catalysts. © 2013 American Chemical Society.

  19. Assembly of influenza hemagglutinin trimers and its role in intracellular transport

    International Nuclear Information System (INIS)

    The hemagglutinin (HA) of influenza virus is a homotrimeric integral membrane glycoprotein. It is cotranslationally inserted into the endoplasmic reticulum as a precursor called HA0 and transported to the cell surface via the Golgi complex. The authors have, in this study, investigated the kinetics and cellular location of the assembly reaction that results in HA0 trimerization using [35S]-methionine. Three independent criteria were used for determining the formation of quaternary structure: the appearance of an epitope recognized by trimer-specific monoclonal antibodies; the acquisition of trypsin resistance, a characteristic of trimers; and the formation of stable complexes which cosedimented with the mature Ha0 trimer (9S/sub 20,w/) in sucrose gradients containing triton X-100. The results showed that oligomer formation is a posttranslational event, occurring with a half time of ∼7.5 min after completion of synthesis. Assembly occurs in the endoplasmic reticulum, followed almost immediately by transport to the Golgi complex. A stabilization event in trimer structure occurs when HA0 leaves the Golgi complex or reaches the plasma membrane. Approximately 10% of the newly synthesized HA0 formed aberrant trimers which were not transported from the endoplasmic reticulum to the Golgi complex or the plasma membrane. Taken together the results suggested that formation of correctly folded quaternary structure constitutes a key event regulating the transport of the protein out of the endoplasmic reticulum. Further changes in subunit interactions occur as the trimers move along the secretory pathway

  20. A theoretical study of five water/ammonia/formaldehyde cyclic trimers: Influence of cooperative effects

    Science.gov (United States)

    Masella, Michel; Flament, Jean-Pierre

    1999-04-01

    Ab initio computations at the MP2 level on five dimers and five cyclic trimers, drawn from water, ammonia, and formaldehyde are presented. Trimers have been drawn to present cyclic X-H---Y patterns. Particular attentions have been devoted in analyzing the energetic contributions resulting from cooperative effects in the trimer binding energies (BEs) and in analyzing the trends of several parameters from monomers to dimers and from dimers to trimers [in particular, the trends of the R(X-H) bond lengths, of the R(X---Y) distances, of the δvXH shifts in the vXH stretch vibrational frequencies, and of the electronic density ρc value at the XH---Y axis critical point when it exists]. The results have exhibited that cooperative effects represent from 10% to 16% of the trimer BEs and that they reinforce, from dimers to trimers, the trends observed for the above parameters from monomers to dimers. In particular, for "typical" X-H---Y HB (i.e., where X and Y atoms correspond to oxygen or nitrogen atoms), R(X-H) bond lengths are increased within 0.01 Å from monomers to dimers and from dimers to trimers, R(X---Y) distances shortened within 0.18 Å, ρc values increased by about 17% and vXH red-shifted from 18 to 164 cm-1 from dimers to trimers. As contrasted to those HBs the R(X-H) and δvXH parameters corresponding to C-H---Y interaction (with Y=O or N) follows an opposite trend from monomers to dimers and from dimers to trimers (i.e., they are respectively smoothly shortened and blue-shifted). All of these results therefore exhibit the great incidence of cooperative effects on the properties of X-H---Y interactions (corresponding to typical HBs or not), which are of importance to understand the properties of biochemical systems.

  1. Antisymmetric double exchange in trimeric mixed-valence clusters

    International Nuclear Information System (INIS)

    The theory of antisymmetric double exchange (AS DE) interaction is developed for the mixed-valence (MV) trimeric [dn-dn-dn±1] clusters of orbitally non-degenerate ions. Strong isotropic double exchange (DE) and Heisenberg exchange interactions (t-J model) form isotropic trigonal states 2S+1Γi (Γi=A1, A2, E) of the MV trimers. Taking into account the spin-orbit coupling results in the vector-type AS DE interaction in these clusters. For the MV trimers with si=1/2, the Hamiltonian of the AS DE coupling has the form HASDEZ=2iΣαβKαβZT-circumflexαβ(SβZ-SαZ), where KαβZ is the antisymmetric (K→ij=-K→ji) vector parameter of the AS DE interaction and Tαβ is the isotropic transfer operator. The operator HASDEZ describes the vector-type spin-transfer interaction induced by the spin-orbit coupling. The microscopic consideration of the AS DE coupling shows that the vector AS DE parameter K→ij is linearly proportional to the spin-orbit coupling constant λ and electron transfer parameter t. The AS DE coupling results in the new effect: the linear AS DE splittings Δ of the 2S+1E DE terms, Δ are proportional to the cluster AS DE parameter KZ=(KabZ+KbcZ+KcaZ)/3. The vector of the AS DE interaction is directed along the trigonal Z-axis: KZ≠0, KX=KY=0. For the delocalized [d9-d10-d10] ([Cu(II)Cu2(I)]) cluster, the linear AS DE fine splitting Δ=2KZ√3 of the ground 2E DE term determines strong anisotropy of the Zeeman splitting, axial anisotropy of g-factors, and magnetic properties. The AS DE coupling mixes the 2S+1A1 and 2S'+1A2, 2S+1E and 2S'+1E' DE terms, ΔS=0,±1. The mixing of the DE levels 2S+1Γi by the AS DE coupling and Dzialoshinsky-Moriya AS exchange (HDM=ΣαβG→αβ[S→αxS→β]) determines the second-order AS contributions {∼[(n1KZ+n2GZ)2/(n3t+n4J)], KZ>>GZ, GZ=(GabZ+GbcZ+GcaZ)/3} to the cluster zero-field splitting (ZFS) parameters DS(2S+1Γi) of the axial anisotropy (HAN=DS(2S+1Γi)[Sz2-S(S+1)/3], DSZ). The second-order AS DE

  2. Targeting Protein-Protein Interactions with Trimeric Ligands: High Affinity Inhibitors of the MAGUK Protein Family

    DEFF Research Database (Denmark)

    Nissen, Klaus B; Kedström, Linda Maria Haugaard; Wilbek, Theis S;

    2015-01-01

    related MAGUK proteins contain three consecutive PDZ domains, hence we envisioned that targeting all three PDZ domains simultaneously would lead to more potent and potentially more specific interactions with the MAGUK proteins. Here we describe the design, synthesis and characterization of a series of...... trimeric ligands targeting all three PDZ domains of PSD-95 and the related MAGUK proteins, PSD-93, SAP-97 and SAP-102. Using our dimeric ligands targeting the PDZ1-2 tandem as starting point, we designed novel trimeric ligands by introducing a PDZ3-binding peptide moiety via a cysteine-derivatized NPEG...... linker. The trimeric ligands generally displayed increased affinities compared to the dimeric ligands in fluorescence polarization binding experiments and optimized trimeric ligands showed low nanomolar inhibition towards the four MAGUK proteins, thus being the most potent inhibitors described. Kinetic...

  3. Bose-Einstein Condensate of Trimers Dressed by Atom-Dimer Cooper Pairs

    CERN Document Server

    Mackie, M; Dannenberg, O; Mackie, Matt; Piilo, Jyrki; Dannenberg, Olavi

    2004-01-01

    We theoretically examine the neutral atom-molecule analogue of the anomalous quantum correlations between degenerate electrons, i.e., Cooper pairs, that are responsible for superconductivity. Based on rogue dissociation of triatomic molecules (trimers) into opposite-momentum pairs of atoms and diatomic molecules (dimers) via a photoassociation or Feshbach resonance, we find a superfluid transition to a Bose-Einstein condensate of trimers dressed by atom-dimer Cooper pairs, at a critical temperature in reach of present ultracold technology.

  4. Virulence-associated trimeric autotransporters of Haemophilus parasuis are antigenic proteins expressed in vivo

    OpenAIRE

    Olvera, Alex; Pina, Sonia; Pérez-Simó, Marta; Oliveira, Simone; Bensaid, Albert

    2010-01-01

    International audience Glässer's disease is a re-emerging swine disease characterized by a severe septicaemia. Vaccination has been widely used to control the disease, although there is a lack of extended cross-protection. Trimeric autotransporters, a family of surface exposed proteins implicated in host-pathogen interactions, are good vaccine candidates. Members of this family have been described in Haemophilus parasuis and designated as virulence-associated trimeric autotransporters (Vta...

  5. Coherent atom-trimer conversion in a repulsive bose-einstein condensate

    International Nuclear Information System (INIS)

    In our recent work, we studied the constructive interference between two chemical reaction channels in the process of coherent atom- trimer conversion in a repulsive atomic Bose condensate. This interference can be viewed as a double-slit-like interference in quantum degenerate matter-wave chemistry (superchemistry). The constructive interference can lead to a significant enhancement of trimer production, leading to a new technique for coherent assembly and control of ultracold heteronuclear molecules. (authors)

  6. Architecture of beta-barrel membrane proteins: analysis of trimeric porins.

    OpenAIRE

    Seshadri, K.; Garemyr, R.; Wallin, E.; von Heijne, G; Elofsson, A.

    1998-01-01

    We have analyzed the known three-dimensional structures of trimeric porins from bacterial outer membranes. The distribution of surface-exposed residues in a direction perpendicular to the membrane is similar to that in helical membrane proteins, with aliphatic residues concentrated in the central 20 A of the bilayer. Outside these residues is a layer of aromatic residues, followed by polar and charged residues. Residues in the trimer interface are more conserved than residues not in the inter...

  7. Waterborne Polyurethane-Polyacrylic Ester Hybrid Dispersion Modified by Hexamethylene Diisocyanate Trimer%Waterborne Polyurethane-Polyacrylic Ester Hybrid Dispersion Modified by Hexamethylene Diisocyanate Trimer

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    A self-emulsifying waterborne polyurethane dispersion was synthesized with both hexamethylene diisocyanate (HDI) trimer and toluene diisoeyanate (TDI), polyether diols N220, 1,4- butanediol(BDO), 2-hydroxymethyl-propionic acid(DMPA) and epoxy resin E-20 as main raw materials with acetone-based method. The dispersion was further modified by methyl methacrylate (MMA) to form a kind of nuclear-shell hybrid dispersion, in which the hydrophobic nuclear was the polymethyl methacrylate and the hydrophilic shell was the self-emulsifying waterborne polyurethane dispersion modified by HDI trimer.

  8. Associations of Escherichia coli K-12 OmpF trimers with rough and smooth lipopolysaccharides

    International Nuclear Information System (INIS)

    The associations of both rough and smooth lipopolysaccharides (LPS) with the OmpF porin of Escherichia coli K-12 were examined in galE strains deleted for ompC. Transformation with pSS37 and growth with galactose conferred the ability to assemble a Shigella dysenteriae O antigen onto the core oligosaccharide of E. coli K-12 LPS. The association of LPS with OmpF trimers was assessed by staining, autoradiography of LPS specifically labeled with [1-14C]galactose, and Western immunoblotting with a monoclonal antibody specific for OmpF trimers. These techniques revealed that the migration distances and multiple banding patterns of OmpF porin trimers in sodium dodecyl sulfate-polyacrylamide gels were dictated by the chemotype of associated LPS. Expression of smooth LPS caused almost all of the trimeric OmpF to run in gels with a slower mobility than trimers from rough strains. The LPS associated with trimers from a smooth strain differed from the bulk-phase LPS by consisting almost exclusively of molecules with O antigen

  9. Possible novel therapy for malignant gliomas with secretable trimeric TRAIL.

    Directory of Open Access Journals (Sweden)

    Moonsup Jeong

    Full Text Available Malignant gliomas are the most common primary brain tumors. Despite intensive clinical investigation and many novel therapeutic approaches, average survival for the patients with malignant gliomas is only about 1 year. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL has shown potent and cancer-selective killing activity and drawn considerable attention as a promising therapy for cancers, but concerns over delivery and toxicity have limited progress. We have developed a secretable trimeric TRAIL (stTRAIL and here evaluated the therapeutic potential of this stTRAIL-based gene therapy in brain tumors. An adenovirus (Ad-stTRAIL delivering stTRAIL was injected into intra-cranial human glioma tumors established in nude mice and tumor growth monitored using the magnetic resonance imaging (MRI. Ad-stTRAIL gene therapy showed potent tumor suppressor activity with no toxic side effects at therapeutically effective doses. When compared with 1, 3-bis(2-chloroethyl-1-nitrosourea (BCNU, a conventional therapy for malignant gliomas, Ad-stTRAIL suppressed tumor growth more potently. The combination of Ad-stTRAIL and BCNU significantly increased survival compared to the control mice or mice receiving Ad-stTRAIL alone. Our data indicate that Ad-stTRAIL, either alone or combined with BCNU, has promise as a novel therapy for malignant gliomas.

  10. Charge transfer along DNA dimers, trimers and polymers

    CERN Document Server

    Simserides, Constantinos

    2013-01-01

    The transfer of electrons and holes along DNA dimers, trimers and polymers is described at the base-pair level, using the relevant on-site energies of the base-pairs and the hopping parameters between successive base-pairs. The temporal and spatial evolution of carriers along a $N$ base-pair DNA segment is determined, solving a system of $N$ coupled differential equations. Useful physical quantities are calculated including the pure mean carrier transfer rate $k$, the inverse decay length $\\beta$ used for exponential fit ($k = k_0 \\textrm{exp}(-\\beta d)$) of the transfer rate as a function of the charge transfer distance $d = N \\times$ 3.4 {\\AA} and the exponent $\\eta$ used for a power law fit ($k = k_0' N^{-\\eta}$) of the transfer rate as function of the number of monomers $N$. Among others, the electron and hole transfer along the polymers poly(dG)-poly(dC), poly(dA)-poly(dT), GCGCGC..., ATATAT... is studied. $\\beta$ ($\\eta$) falls in the range $\\approx$ 0.2 - 2 {\\AA}$^{-1}$ (1.7 - 17), $k_0$ ($k_0'$) is us...

  11. Spin and orbital magnetism of coinage metal trimers (Cu3, Ag3, Au3: A relativistic density functional theory study

    Directory of Open Access Journals (Sweden)

    Mahdi Afshar

    2013-11-01

    Full Text Available We have demonstrated electronic structure and magnetic properties of Cu3, Ag3 and Au3 trimers using a full potential local orbital method in the framework of relativistic density functional theory. We have also shown that the non-relativistic generalized gradient approximation for the exchange-correlation energy functional gives reliable magnetic properties in coinage metal trimers compared to experiment. In addition we have indicated that the spin-orbit coupling changes the structure and magnetic properties of gold trimer while the structure and magnetic properties of copper and silver trimers are marginally affected. A significant orbital moment of 0.21μB was found for most stable geometry of the gold trimer whereas orbital magnetism is almost quenched in the copper and silver trimers.

  12. Tunable trimers: Using temperature and pressure to control luminescent emission in gold(I) pyrazolate-based trimers

    International Nuclear Information System (INIS)

    A systematic investigation into the relationship between the solid-state luminescence and the intermolecular Au···Au interactions in a series of pyrazolate-based gold(I) trimers; tris(μ2-pyrazolato-N,N')-tri-gold(I) (1), tris(μ2-3,4,5-trimethylpyrazolato-N,N')-tri-gold(I) (2), tris(μ2-3-methyl-5-phenylpyrazolato-N,N')-tri-gold(I) (3) and tris(μ2-3,5-diphenylpyrazolato-N,N')-tri-gold(I) (4) has been carried out using variable temperature and high pressure X-ray crystallography, solid-state emission spectroscopy, Raman spectroscopy and computational techniques. Single-crystal X-ray studies show that there is a significant reduction in the intertrimer Au···Au distances both with decreasing temperature and increasing pressure. In the four complexes, the reduction in temperature from 293 to 100 K is accompanied by a reduction in the shortest intermolecular Au···Au contacts of between 0.04 and 0.08 Å. The solid-state luminescent emission spectra of 1 and 2 display a red shift with decreasing temperature or increasing pressure. Compound 3 does not emit under ambient conditions but displays increasingly red-shifted luminescence upon cooling or compression. Compound 4 remains emissionless, consistent with the absence of intermolecular Au···Au interactions. The largest pressure induced shift in emission is observed in 2 with a red shift of approximately 630 cm-1 per GPa between ambient and 3.80 GPa. The shifts in all the complexes can be correlated with changes in Au···Au distance observed by diffraction

  13. Quantum entanglement in trimer spin-1/2 Heisenberg chains with antiferromagnetic coupling

    CERN Document Server

    Del Cima, O M; da Silva, S L L

    2015-01-01

    The quantum entanglement measure is determined, for the first time, for antiferromagnetic trimer spin-1/2 Heisenberg chains. The physical quantity proposed to measure the entanglement is the distance between states by adopting the Hilbert-Schmidt norm. The method is applied to the new magnetic Cu(II) trimer system, 2b.3CuCl_2.2H_2O, and to the trinuclear Cu(II) halide salt, (3MAP)_2Cu_2Cl_8. The decoherence temperature, above which the entanglement is suppressed, is determined for the both systems. A correlation among their decoherence temperatures and their respective exchange coupling constants is established.

  14. Non-Hermitian trimers: PT-symmetry versus pseudo-Hermiticity

    Science.gov (United States)

    Suchkov, Sergey V.; Fotsa-Ngaffo, Fernande; Kenfack-Jiotsa, Aurelien; Tikeng, Arnaud D.; Kofane, Timoleon C.; Kivshar, Yuri S.; Sukhorukov, Andrey A.

    2016-06-01

    We study a structure composed of three coupled waveguides with gain and loss, a non-Hermitian trimer. We demonstrate that the mode spectrum can be entirely real if the waveguides are placed in a special order and at certain distances between each other. Such structures generally lack a spatial symmetry, in contrast to parity-time symmetric trimers which are known to feature a real spectrum. We also determine a threshold for wave amplification and analyse the scattering properties of such non-conservative systems embedded into a chain of conservative waveguides.

  15. Cleavage-Independent HIV-1 Env Trimers Engineered as Soluble Native Spike Mimetics for Vaccine Design

    Directory of Open Access Journals (Sweden)

    Shailendra Kumar Sharma

    2015-04-01

    Full Text Available Viral glycoproteins mediate entry by pH-activated or receptor-engaged activation and exist in metastable pre-fusogenic states that may be stabilized by directed rational design. As recently reported, the conformationally fixed HIV-1 envelope glycoprotein (Env trimers in the pre-fusion state (SOSIP display molecular homogeneity and structural integrity at relatively high levels of resolution. However, the SOSIPs necessitate full Env precursor cleavage, which requires endogenous furin overexpression. Here, we developed an alternative strategy using flexible peptide covalent linkage of Env subdomains to produce soluble, homogeneous, and cleavage-independent Env mimics, called native flexibly linked (NFL trimers, as vaccine candidates. This simplified design avoids the need for furin co-expression and, in one case, antibody affinity purification to accelerate trimer scale-up for preclinical and clinical applications. We have successfully translated the NFL design to multiple HIV-1 subtypes, establishing the potential to become a general method of producing native-like, well-ordered Env trimers for HIV-1 or other viruses.

  16. Structure of Acidic pH Dengue Virus Showing the Fusogenic Glycoprotein Trimers

    NARCIS (Netherlands)

    Zhang, Xinzheng; Sheng, Ju; Austin, S. Kyle; Hoornweg, Tabitha E.; Smit, Jolanda M.; Kuhn, Richard J.; Diamond, Michael S.; Rossmann, Michael G.

    2015-01-01

    Flaviviruses undergo large conformational changes during their life cycle. Under acidic pH conditions, the mature virus forms transient fusogenic trimers of E glycoproteins that engage the lipid membrane in host cells to initiate viral fusion and nucleocapsid penetration into the cytoplasm. However,

  17. Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L; White, Mitchell R; Tecle, Tesfaldet;

    2007-01-01

    neutralize the virus. We then purified natural human trimeric and multimeric forms of SP-D from amniotic fluid and tested ability of these preparations to bind to IAV, to inhibit infectivity and hemagglutination activity of IAV in vitro. RESULTS: In initial experiments mAbs directed against different areas....../Thr 11 form of SP-D is associated with low serum levels and assembles predominantly as trimers as opposed to the more common multimeric forms of SP-D. METHODS: Preliminary experiments were done to establish the effects of different monoclonal antibodies against SP-D on ability of SP-D to bind to or...... on the CRD of SP-D were found to have differing effects on antiviral activity. Using an mAb that did not interfere with antiviral activity of SP-D, we confirm that natural SP-D trimers had reduced ability to bind to IAV. In addition, the trimers had reduced ability to neutralize IAV as compared to...

  18. Selected HIV-1 Env trimeric formulations act as potent immunogens in a rabbit vaccination model

    DEFF Research Database (Denmark)

    Heyndrickx, Leo; Stewart-Jones, Guillaume; Jansson, Marianne Bendixen; Schuitemaker, Hanneke; Bowles, Emma; Buonaguro, Luigi; Grevstad, Berit; Vinner, Lasse; Vereecken, Katleen; Parker, Joe; Ramaswamy, Meghna; Biswas, Priscilla; Vanham, Guido; Scarlatti, Gabriella; Fomsgaard, Anders

    2013-01-01

    Ten to 30% of HIV-1 infected subjects develop broadly neutralizing antibodies (bNAbs) during chronic infection. We hypothesized that immunizing rabbits with viral envelope glycoproteins (Envs) from these patients may induce bNAbs, when formulated as a trimeric protein and in the presence of an...

  19. The nature of spin trimer in Ca3Cu2Ni(PO4)4

    International Nuclear Information System (INIS)

    The nature of spin trimer and 3d spin dynamics in Ca3Cu2Ni(PO4)4 was studied using 31P NMR measurements. This material is obtained replacing one of the Cu ions by a Ni ion in one dimensional spin trimer compound Ca3Cu3(PO4)4. NMR spectrum suggests the presence of two types of magnetically inequivalent phosphorous atoms as in the parent compound. This finding reveals the presence of only one type of trimer viz. Cu2-Cu1-Cu2 rather than three types viz., Cu2-Cu1-Cu2, Cu2-Cu1-Ni and Ni-Cu1-Ni as suggested from neutron scattering. Hence the ground state of Ca3Cu2Ni(PO4)4 appears to be a quintet. The present finding also explains the magnetic susceptibility behavior showing no indication of the reduction of net spin of a trimer in Ca3Cu2Ni(PO4)4, as expected for JNi-Cu = - 0.85 meV compared to JCu-Cu = - 4.74 meV, reported from neutron scattering. The spin lattice relaxation rate suggests that the three magnon mediated scattering process, dominant in Ca3Cu3(PO4)4, is reduced in Ca3Cu2Ni(PO4)4.

  20. Theory vs. experiment for molecular clusters: Spectra of OCS trimers and tetramers

    International Nuclear Information System (INIS)

    All singly substituted 13C, 18O, and 34S isotopomers of the previously known OCS trimer are observed in natural abundance in a broad-band spectrum measured with a chirped-pulse Fourier transform microwave spectrometer. The complete substitution structure thus obtained critically tests (and confirms) the common assumption that monomers tend to retain their free structure in a weakly bound cluster. A new OCS trimer isomer is also observed, and its structure is determined to be barrel-shaped but with the monomers all approximately aligned, in contrast to the original trimer which is barrel-shaped with two monomers aligned and one anti-aligned. An OCS tetramer spectrum is assigned for the first time, and the tetramer structure resembles an original trimer with an OCS monomer added at the end with two sulfur atoms. Infrared spectra observed in the region of the OCS ν1 fundamental (≈2060 cm−1) are assigned to the same OCS tetramer, and another infrared band is tentatively assigned to a different tetramer isomer. The experimental results are compared and contrasted with theoretical predictions from the literature and from new cluster calculations which use an accurate OCS pair potential and assume pairwise additivity

  1. Temperature dependent dynamics of DegP-trimer: A molecular dynamics study

    Directory of Open Access Journals (Sweden)

    Nivedita Rai

    2015-01-01

    Full Text Available DegP is a heat shock protein from high temperature requirement protease A family, which reacts to the environmental stress conditions in an ATP independent way. The objective of the present analysis emerged from the temperature dependent functional diversity of DegP between chaperonic and protease activities at temperatures below and above 28 °C, respectively. DegP is a multimeric protein and the minimal functional unit, DegP-trimer, is of great importance in understanding the DegP pathway. The structural aspects of DegP-trimer with respect to temperature variation have been studied using molecular dynamics simulations (for 100 ns and principal component analysis to highlight the temperature dependent dynamics facilitating its functional diversity. The DegP-trimer revealed a pronounced dynamics at both 280 and 320 K, when compared to the dynamics observed at 300 K. The LA loop is identified as the highly flexible region during dynamics and at extreme temperatures, the residues 46–80 of LA loop express a flip towards right (at 280 and left ( at 320 K with respect to the fixed β-sheet connecting the LA loop of protease for which Phe46 acts as one of the key residues. Such dynamics of LA loop facilitates inter-monomeric interaction with the PDZ1 domain of the neighbouring monomer and explains its active participation when DegP exists as trimer. Hence, the LA loop mediated dynamics of DegP-trimer is expected to provide further insight into the temperature dependent dynamics of DegP towards the understanding of its assembly and functional diversity in the presence of substrate.

  2. Repressive mutations restore function-loss caused by the disruption of trimerization in Escherichia coli multidrug transporter AcrB

    Directory of Open Access Journals (Sweden)

    Zhaoshuai eWang

    2015-01-01

    Full Text Available AcrAB-TolC and their homologs are major multidrug efflux systems in Gram-negative bacteria. The inner membrane component AcrB functions as a trimer. Replacement of Pro223 by Gly in AcrB decreases the trimer stability and drastically reduces the drug efflux activity. The goal of this study is to identify suppressor mutations that restore function to mutant AcrBP223G and explore the mechanism of function recovery. Two methods were used to introduce random mutations into the plasmid of AcrBP223G. Mutants with elevated drug efflux activity were identified, purified, and characterized to examine their expression level, trimer stability, interaction with AcrA, and substrate binding. Nine single-site repressor mutations were identified, including T199M, D256N, A209V, G257V, M662I, Q737L, D788K, P800S, and E810K. Except for M662I, all other mutations located in the docking region of the periplasmic domain. While three mutations, T199M, A209V, and D256N, significantly increased the trimer stability, none of them restored the trimer affinity to the wild type level. M662, the only site of mutation that located in the porter domain, was involved in substrate binding. Our results suggest that the function loss resulted from compromised AcrB trimerization could be restored through various mechanisms involving the compensation of trimer stability and substrate binding.

  3. Computational study of trimer self-assembly and fluid phase behavior

    International Nuclear Information System (INIS)

    The fluid phase diagram of trimer particles composed of one central attractive bead and two repulsive beads was determined as a function of simple geometric parameters using flat-histogram Monte Carlo methods. A variety of self-assembled structures were obtained including spherical micelle-like clusters, elongated clusters, and densely packed cylinders, depending on both the state conditions and shape of the trimer. Advanced simulation techniques were employed to determine transitions between self-assembled structures and macroscopic phases using thermodynamic and structural definitions. Simple changes in particle geometry yield dramatic changes in phase behavior, ranging from macroscopic fluid phase separation to molecular-scale self-assembly. In special cases, both self-assembled, elongated clusters and bulk fluid phase separation occur simultaneously. Our work suggests that tuning particle shape and interactions can yield superstructures with controlled architecture

  4. The Symmetry Protected Piecewise Berry Phases, Enhanced Pumping and Non-reciprocity in Trimer Lattices

    CERN Document Server

    Liu, Xuele

    2016-01-01

    Finding new phase is a fundamental task in physics. Landau's theory explained the deep connection between symmetry breaking and phase transition commonly occurring in magnetic, superconducting and super uid systems. The discovery of the quantum Hall effect led to Z topological phases which could be different for same symmetry and are characterized by the discrete values of the Berry phases. By studying 1D trimer lattices we report new phases characterized by Berry phases which are piecewise continuous rather than discrete numbers. The phase transition occurs at the discontinuity point. With time-dependent changes, trimer lattices also give a 2D phases characterized by very specific 2D Berry phases of half period. These Berry phases change smoothly within a phase while change discontinuously at the transition point. We further demonstrate the existence of adiabatic pumping for each phase and gain assisted enhanced pumping. The non-reciprocity of the pumping process makes the system a good optical diode.

  5. Dynamics of Spatially Confined Bisphenol A Trimers in a Unimolecular Network on Ag(111).

    Science.gov (United States)

    Lloyd, Julian A; Papageorgiou, Anthoula C; Fischer, Sybille; Oh, Seung Cheol; Saǧlam, Özge; Diller, Katharina; Duncan, David A; Allegretti, Francesco; Klappenberger, Florian; Stöhr, Martin; Maurer, Reinhard J; Reuter, Karsten; Reichert, Joachim; Barth, Johannes V

    2016-03-01

    Bisphenol A (BPA) aggregates on Ag(111) shows a polymorphism between two supramolecular motifs leading to formation of distinct networks depending on thermal energy. With rising temperature a dimeric pairing scheme reversibly converts into a trimeric motif, which forms a hexagonal superstructure with complex dynamic characteristics. The trimeric arrangements notably organize spontaneously into a self-assembled one-component array with supramolecular BPA rotors embedded in a two-dimensional stator sublattice. By varying the temperature, the speed of the rotors can be controlled as monitored by direct visualization. A combination of scanning tunneling microscopy and dispersion-corrected density-functional tight-binding (DFTB-vdW(surf)) based molecular modeling reveals the exact atomistic position of each molecule within the assembly as well as the driving force for the formation of the supramolecular rotors. PMID:26849384

  6. Trimerization catalysis of phenylisocyanate in the presence of phenolic mannich bases

    Energy Technology Data Exchange (ETDEWEB)

    Selivanov, A.V.; Zenitova, L.A.; Bakirova, I.N.; Kirpichnikov, P.A.

    1988-11-01

    The kinetics of the cyclic trimerization of phenylisocyanate in the presence of phenolic Mannich bases have been studied by IR spectroscopy; a catalysis mechanism for the reaction is proposed. It was found that in order for trimerization to occur the catalyst molecule must contain both a hydroxyl group and a tertiary nitrogen atom, which leads to reaction at the OH group of the catalyst and its conversion via a urethane derivative to an allophanate; the latter species undergoes tautomeric rearrangement to a bipolar ion, which is the actual catalysis site. The effects of the number of aminomethyl, hydroxyl, and other electron-donating and electron-withdrawing substituents on the structure of Mannich bases have also been investigated.

  7. Evidence for an Excited-State Efimov Trimer in a Three-Component Fermi Gas

    International Nuclear Information System (INIS)

    We observe enhanced three-body recombination in a three-component 6Li Fermi gas attributable to an excited Efimov trimer state intersecting the three-atom scattering threshold near 895 G. From measurements of the recombination rate we determine the Efimov parameters κ* and η* for the universal region above 600 G which includes three overlapping Feshbach resonances. The value of κ* also predicts the locations of loss features previously observed near 130 and 500 G [T. B. Ottenstein et al., Phys. Rev. Lett. 101, 203202 (2008); J. H. Huckans et al., Phys. Rev. Lett. 102, 165302 (2009)] suggesting they are associated with a ground-state Efimov trimer near threshold. We also report on the realization of a degenerate three-component Fermi gas with approximate SU(3) symmetry.

  8. Surface Induced Dissociations and Reactions of Acetonitrile Monomer, Dimer and Trimer Ions

    Czech Academy of Sciences Publication Activity Database

    Mair, C.; Herman, Zdeněk; Fedor, J.; Lezius, M.; Märk, T. D.

    2003-01-01

    Roč. 118, č. 3 (2003), s. 1479-1486. ISSN 0021-9606 R&D Projects: GA ČR GA203/00/0632 Grant ostatní: Cooperation PST (AT) 2000-06 Institutional research plan: CEZ:AV0Z4040901 Keywords : surface-induced * acetonitrile monomer * trimer ions Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.950, year: 2003

  9. Are there Efimov trimers in hexafluorobenzene rather than in benzene vapor itself?

    International Nuclear Information System (INIS)

    Is there a spectroscopic method to detect an Efimov state? Following our proposal of an Efimov state arising from three pseudo bosons (generalized Cooper pairs) in benzene, our spectroscopic studies have found no evidence of Efimov trimers (ET) in h6- or d6-benzene. However, hexafluoro-benzene has shown peaks that we attributed to ET and the pseudo bosons. The experimental evidence suggests that benzene pseudo bosons and subsequently ET are quite sensitive to the surroundings

  10. Bouncing trimer: a random self-propelled particle, chaos and periodical motions

    Science.gov (United States)

    Dorbolo, S.; Ludewig, F.; Vandewalle, N.

    2009-03-01

    A trimer is an object composed of three centimetrical stainless steel beads equidistant from each other and is predestined to show richer behaviour than a bouncing ball or a bouncing dimer. A rigid trimer was placed on the plate of an electromagnetic shaker and was vertically vibrated according to a sinusoidal signal. The horizontal translational and rotational motions of the trimer were recorded for a range of frequencies between 25 and 100 Hz, while the amplitude of the forcing vibration was tuned to obtain maximal acceleration of the plate up to 10 times gravity. Several modes have been detected such as, e.g., rotational and pure translational motions. These modes are found at determined accelerations of the plate and do not depend on the frequency. Chaotic behaviour is observed for other accelerations. By recording the time delays between two successive contacts when the frequency and the amplitude are fixed, a map of the bouncing regime was constructed and compared with that of the dimer and the bouncing ball. Period-2 and period-3 orbits were experimentally observed. In these modes, according to observations, the contact between the trimer and the plate is persistent between two successive jumps. This persistence erases the memory of the jump preceding the contact. A model based on the conditions for obtaining persistent contact is proposed and allows us to explain the values of the particular accelerations for which period-2 and period-3 modes were observed. Finally, numerical simulations allow us to reproduce the experimental results. This allows us to conclude that the friction between the beads and the plate is the major dissipative process.

  11. Wettability alteration by trimeric cationic surfactant at water-wet/oil-wet mica mineral surfaces

    International Nuclear Information System (INIS)

    The wettability of oil reservoir rock affects the efficiency of the oil recovery process by reducing the capillary force. Methyldodecylbis [2-(dimethyldodecylammonio) ethyl] ammonium tribromide is a trimeric cationic surfactant that contains three dodecyl chains and three quaternary ammonium head groups connected by divinyl groups. The surfactant was synthesized, purified and used as a new wetting alteration agent. This paper focuses on the ability of this trimeric cationic surfactant to alter the wettability of water-wet and oil-wet mica mineral surfaces. The contact angle data of the solid-liquid interface in oil/water/solid three-phase system show that the trimeric cationic surfactant, when compared with single- and double-chain cationic surfactant, is a more effective wetting agent for water-wet and oil-wet mica surfaces at lower concentration. Measurements by atomic force microscopy (AFM) show that the surfactant molecules have formed a monolayer to reverse the wetting properties. On the water-wet surface, the surface is suffused with negative charge, which could attract the cationic head of surfactant, and leave the hydrophobic tails exposed. In contrast, on the oil-wet surface, the hydrophobic tails were attracted by hydrophobic interactions to the oil film between the surfactant and the crude oil. The hydrophilic heads were left outside to form a hydrophilic layer, which could explain the wettable to hydrophilic trend. Alteration to the degree of wettability is mainly dependent on the adsorption areas of the surfactant. The data show that the ability of the trimeric cationic surfactant affect the wettability is independent of surface tension.

  12. ENERGY TRANSFER IN TRIMERIC C-PHYCOCYANIN STUDIED BY PICOSECOND FLUORESCENCE KINETICS

    OpenAIRE

    WENDLER, J.; John, Wolfhart; Scheer, Hugo; Holzwarth, A. R.

    1986-01-01

    The excited state kinetics of trimeric C-phycocyanin from Mastigocladus laminosus has been measured as a function of the emission and excitation wavelength by the single-photon timing technique with picosecond resolution and simultaneous data analysis. A fast decay component of 22 ps (C-phycocyanin with linker peptides) and 36 ps (C-phycocyanin lacking linker peptides) is attributed to efficient energy transfer from sensitizing to fluorescing chromophores. At long detection wavelengths the fa...

  13. Homogeneous and heterogeneous cyclopentadienyl-arene titanium catalysts for selective ethylene trimerization to 1-hexene

    Czech Academy of Sciences Publication Activity Database

    Varga, Vojtěch; Hodík, Tomáš; Lamač, Martin; Horáček, Michal; Zukal, Arnošt; Žilková, Naděžda; Parker Jr., W. O.; Pinkas, Jiří

    2015-01-01

    Roč. 777, FEB 2015 (2015), s. 57-66. ISSN 0022-328X R&D Projects: GA ČR GBP106/12/G015; GA ČR(CZ) GAP207/12/2368; GA ČR(CZ) GA14-08531S Institutional support: RVO:61388955 Keywords : Cyclopentadienyl-arene complexes * Ethylene trimerization * SBA-15 Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.173, year: 2014

  14. Helical -type aggregation of trimeric -phenylene vinylene with chiral ester groups

    Indian Academy of Sciences (India)

    Haiquan Zhang; Ying Li; Peng Wang

    2011-08-01

    Self-assembly properties of the trimeric -phenylene vinylene derivative containing symmetrical endgroups of -(+)-2-methylbutyric acid ester (ChTPV) in H2O/THF mixed solvents were studied by absorption, photoluminescence and circular dichroism (CD) spectra. The results indicate that ChTPV exhibits helical -type nano-aggregates in 80% H2O/THFmixed solvents, and the negative exciton coupling suggests that the chromophoric dipoles are oriented in a counter-clockwise direction.

  15. Selective ethylene trimerization: A study into the mechanism and the reduction of PE formation

    OpenAIRE

    Kretschmer, WP; van Buren, FR; Hessen, B.; van Oeffelen, DA; Oeffelen, Dominicus A. van; Hagen, H.

    2006-01-01

    In the present study, the titanium-catalyzed ethylene trimerization in general, and more specifically, the concomitant PE formation have been studied. The polymer formation is undesirable as it not only will lead to lower I-hexene yields, but it can cause reactor fouling under the applied conditions (30-80 degrees C, toluene solvent). It is, therefore, important to know which factors are involved in the formation of polymeric products and how their formation can be reduced or even prevented. ...

  16. Ab initio study of intermolecular potential of H2O trimer

    OpenAIRE

    Chalasinski, G.; Szczesniak, M. M.; Cieplak, P; Scheiner, Steve

    1991-01-01

    Nonadditive contribution to the interaction energy in water trimer is analyzed in terms of Heitler–London exchange, SCF deformation, induction and dispersion nonadditivities. Nonadditivity originates mainly from the SCF deformation effect which is due to electric polarization. However, polarization does not serve as a universal mechanism for nonadditivity in water. In the double‐donor configuration, for example, the Heitler–London exchange contribution is the most important and polariz...

  17. Manzamenone O, new trimeric fatty acid derivative from a marine sponge Plakortis sp.

    Science.gov (United States)

    Tanaka, Naonobu; Asai, Miki; Takahashi-Nakaguchi, Azusa; Gonoi, Tohru; Fromont, Jane; Kobayashi, Jun'ichi

    2013-05-17

    A new structurally unique trimeric fatty acid derivative, manzamenone O (1), was isolated from a marine sponge Plakortis sp. Manzamenone O (1) has a novel skeleton consisting of C-C bonded octahydroindenone and dioxabicyclo[3.3.0]octane moieties and three long aliphatic chains. The structure of 1 was elucidated on the basis of spectroscopic data and conformational analysis. Manzamenone O (1) exhibited antimicrobial activity against Micrococcus luteus, Aspergillis niger, and Trichophyton mentagrophytes. PMID:23651077

  18. Electron stimulated desorption of anions from native and brominated single stranded oligonucleotide trimers

    Energy Technology Data Exchange (ETDEWEB)

    Polska, Katarzyna; Rak, Janusz [Department of Chemistry, University of Gdansk, Sobieskiego 18, 80-952 Gdansk (Poland); Bass, Andrew D.; Cloutier, Pierre; Sanche, Leon [Research Group in the Radiation Sciences, Faculty of Medicine, Universite de Sherbrooke, Sherbrooke, Quebec J1H 5N4 (Canada)

    2012-02-21

    We measured the low energy electron stimulated desorption (ESD) of anions from thin films of native (TXT) and bromine monosubstituted (TBrXT) oligonucleotide trimers deposited on a gold surface (T = thymidine, X = T, deoxycytidine (C), deoxyadenosine (A) or deoxyguanosine (G), Br = bromine). The desorption of H{sup -}, CH{sub 3}{sup -}/NH{sup -}, O{sup -}/NH{sub 2}{sup -}, OH{sup -}, CN{sup -}, and Br{sup -} was induced by 0 to 20 eV electrons. Dissociative electron attachment, below 12 eV, and dipolar dissociation, above 12 eV, are responsible for the formation of these anions. The comparison of the results obtained for the native and brominated trimers suggests that the main pathways of TBrXT degradation correspond to the release of the hydride and bromide anions. Significantly, the presence of bromine in oligonucleotide trimers blocks the electron-induced degradation of nuclobases as evidenced by a dramatic decrease in CN{sup -} desorption. An increase in the yields of OH{sup -} is also observed. The debromination yield of particular oligonucleotides diminishes in the following order: BrdU > BrdA > BrdG > BrdC. Based on these results, 5-bromo-2{sup '}-deoxyuridine appears to be the best radiosensitizer among the studied bromonucleosides.

  19. Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein

    Directory of Open Access Journals (Sweden)

    Anna-Janina Behrens

    2016-03-01

    Full Text Available The HIV-1 envelope glycoprotein trimer is covered by an array of N-linked glycans that shield it from immune surveillance. The high density of glycans on the trimer surface imposes steric constraints limiting the actions of glycan-processing enzymes, so that multiple under-processed structures remain on specific areas. These oligomannose glycans are recognized by broadly neutralizing antibodies (bNAbs that are not thwarted by the glycan shield but, paradoxically, target it. Our site-specific glycosylation analysis of a soluble, recombinant trimer (BG505 SOSIP.664 maps the extremes of simplicity and diversity of glycan processing at individual sites and reveals a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, we identify examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens.

  20. Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein

    Science.gov (United States)

    Behrens, Anna-Janina; Vasiljevic, Snezana; Pritchard, Laura K.; Harvey, David J.; Andev, Rajinder S.; Krumm, Stefanie A.; Struwe, Weston B.; Cupo, Albert; Kumar, Abhinav; Zitzmann, Nicole; Seabright, Gemma E.; Kramer, Holger B.; Spencer, Daniel I.R.; Royle, Louise; Lee, Jeong Hyun; Klasse, Per J.; Burton, Dennis R.; Wilson, Ian A.; Ward, Andrew B.; Sanders, Rogier W.; Moore, John P.; Doores, Katie J.; Crispin, Max

    2016-01-01

    Summary The HIV-1 envelope glycoprotein trimer is covered by an array of N-linked glycans that shield it from immune surveillance. The high density of glycans on the trimer surface imposes steric constraints limiting the actions of glycan-processing enzymes, so that multiple under-processed structures remain on specific areas. These oligomannose glycans are recognized by broadly neutralizing antibodies (bNAbs) that are not thwarted by the glycan shield but, paradoxically, target it. Our site-specific glycosylation analysis of a soluble, recombinant trimer (BG505 SOSIP.664) maps the extremes of simplicity and diversity of glycan processing at individual sites and reveals a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, we identify examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens. PMID:26972002

  1. Techniques and tactics used in determining the structure of the trimeric ebolavirus glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeffrey E.; Fusco, Marnie L.; Abelson, Dafna M.; Hessell, Ann J.; Burton, Dennis R. [Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (United States); Saphire, Erica Ollmann, E-mail: erica@scripps.edu [Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (United States); The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (United States)

    2009-11-01

    Here, the techniques, tactics and strategies used to overcome a series of technical roadblocks in crystallization and phasing of the trimeric ebolavirus glycoprotein are described. The trimeric membrane-anchored ebolavirus envelope glycoprotein (GP) is responsible for viral attachment, fusion and entry. Knowledge of its structure is important both for understanding ebolavirus entry and for the development of medical interventions. Crystal structures of viral glycoproteins, especially those in their metastable prefusion oligomeric states, can be difficult to achieve given the challenges in production, purification, crystallization and diffraction that are inherent in the heavily glycosylated flexible nature of these types of proteins. The crystal structure of ebolavirus GP in its trimeric prefusion conformation in complex with a human antibody derived from a survivor of the 1995 Kikwit outbreak has now been determined [Lee et al. (2008 ▶), Nature (London), 454, 177–182]. Here, the techniques, tactics and strategies used to overcome a series of technical roadblocks in crystallization and phasing are described. Glycoproteins were produced in human embryonic kidney 293T cells, which allowed rapid screening of constructs and expression of protein in milligram quantities. Complexes of GP with an antibody fragment (Fab) promoted crystallization and a series of deglycosylation strategies, including sugar mutants, enzymatic deglycosylation, insect-cell expression and glycan anabolic pathway inhibitors, were attempted to improve the weakly diffracting glycoprotein crystals. The signal-to-noise ratio of the search model for molecular replacement was improved by determining the structure of the uncomplexed Fab. Phase combination with Fab model phases and a selenium anomalous signal, followed by NCS-averaged density modification, resulted in a clear interpretable electron-density map. Model building was assisted by the use of B-value-sharpened electron-density maps and the

  2. Synthesis of Cyclic Porphyrin Trimers through Alkyne Metathesis Cyclooligomerization and Their Host–Guest Binding Study

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Chao; Long, Hai; Jin, Yinghua; Zhang, Wei

    2016-06-17

    Cyclic porphyrin trimers were synthesized through one-step cyclooligomerization via alkyne metathesis from diyne monomers. These macrocycles show interesting host-guest binding interactions with fullerenes, selectively binding C70 (6 x 103 M-1) over C60 and C84 (no binding observed). The fullerene-encapsulated host-guest complex can undergo guest or host exchange in the presence of another guest (2,4,6-tri(4-pyridyl)-1,3,5-triazine) or host (cage COP5) molecule with higher binding affinity.

  3. Interatomic Coulombic decay widths of helium trimer: A diatomics-in-molecules approach.

    Science.gov (United States)

    Sisourat, Nicolas; Kazandjian, Sévan; Randimbiarisolo, Aurélie; Kolorenč, Přemysl

    2016-02-28

    We report a new method to compute the Interatomic Coulombic Decay (ICD) widths for large clusters which relies on the combination of the projection-operator formalism of scattering theory and the diatomics-in-molecules approach. The total and partial ICD widths of a cluster are computed from the energies and coupling matrix elements of the atomic and diatomic fragments of the system. The method is applied to the helium trimer and the results are compared to fully ab initio widths. A good agreement between the two sets of data is shown. Limitations of the present method are also discussed. PMID:26931685

  4. Synthesis of Cyclic Porphyrin Trimers through Alkyne Metathesis Cyclooligomerization and Their Host-Guest Binding Study.

    Science.gov (United States)

    Yu, Chao; Long, Hai; Jin, Yinghua; Zhang, Wei

    2016-06-17

    Cyclic porphyrin trimers were synthesized through one-step cyclooligomerization via alkyne metathesis from diyne monomers. These macrocycles show interesting host-guest binding interactions with fullerenes, selectively binding C70 (6 × 10(3) M(-1)) over C60 and C84 (no binding observed). The fullerene-encapsulated host-guest complex can undergo guest or host exchange in the presence of another guest (2,4,6-tri(4-pyridyl)-1,3,5-triazine) or host (cage COP5) molecule with higher binding affinity. PMID:27267936

  5. Glucagon stop-go kinetics supports a monomer-trimer fibrillation model

    CERN Document Server

    Kosmrlj, Andrej; Kyrsting, Anders; Otzen, Daniel E; Oddershede, Lene B; Jensen, Mogens H

    2014-01-01

    We investigate in vitro fibrillation kinetics of the hormone peptide glucagon at various concentrations using confocal microscopy and determine the glucagon fibril persistence length $60 \\mu\\textrm{m}$. At all concentrations we observe that periods of individual fibril growth are interrupted by periods of stasis. The growth probability is large at high and low concentrations and is reduced for intermediate glucagon concentrations. To explain this behavior we propose a simple model, where fibrils come in two forms, one built entirely from glucagon monomers and one entirely from glucagon trimers. The opposite building blocks act as fibril growth blockers, and this generic model reproduces experimental behavior well.

  6. Variational Study of Fermionic Helium Dimer and Trimer in Two Dimensions

    OpenAIRE

    Vranješ, Leandra; Kilić, Srećko

    2000-01-01

    In variational calculation, we have obtained the binding energy of helium 3 dimer in two dimensions. The existence of one bound State, with the binding energy -0.014 mK, has been definitively found. Also, the existence of a binding state of helium 3 trimer having spin -1/2 with the energy below -0.0057 mK is indicated. This re-opens the question of the existence of the gas phase of many helium 3 atoms on the surface of superfluid helium 4.

  7. Comparison of calculated and experimentally resolved rate constants for excitation energy transfer in C-phycocyanin. 2. Trimers

    Energy Technology Data Exchange (ETDEWEB)

    Debreczeny, M.F.; Sauer, K. [Lawrence Berkeley Lab., CA (United States); Zhou, J.; Bryant, D.A. [Pennsylvania State Univ., University Park, PA (United States)

    1995-05-18

    Resolution of the absorption spectrum of the {beta}{sub 155} chromophore in C-phycocyanin (PC) trimers is achieved by comparison of the steady state absorption spectra of ({alpha}{sup PC}{beta}{sup PC}){sub 3} and ({alpha}{sup PC}{beta}{sup *}){sub 3}. Comparison of the anisotropy decays of ({alpha}{sup PC}{beta}{sup PC}){sub 3} and ({alpha}{sup PC}{beta}{sup *}){sub 3} also greatly aids in the assignment of the dominant kinetic processes in PC trimers. A comparison is made of calculated Foerster rate constants for energy transfer with those rate constants resolved experimentally in the PC trimers. 35 refs.., 10 figs., 2 tabs.

  8. Production and crystallization of the C-propeptide trimer from human procollagen III

    International Nuclear Information System (INIS)

    The first crystallization of a fibrillar procollagen C-propeptide domain, that from human procollagen III, is described. Present throughout the Metaozoa in the form of ∼90 kDa trimers, this domain plays crucial roles in tissue homeostasis and disease. The C-propeptide domains of the fibrillar procollagens, which are present throughout the Metazoa in the form of ∼90 kDa trimers, play crucial roles in both intracellular molecular assembly and extracellular formation of collagen fibrils. The first crystallization of a C-propeptide domain, that from human procollagen III, is described. Following transient expression in mammalian 293T cells of both the native protein and a selenomethionine derivative, two crystal forms of the homotrimer were obtained: an orthorhombic form (P212121) that diffracted to 1.7 Å resolution and a trigonal form (P321) that diffracted to 3.5 Å resolution. Characterization by MALDI-TOF mass spectrometry allowed the efficiency of selenomethionine incorporation to be determined

  9. Rate Constant Change of Photo Reaction of Bacteriorhodopsin Observed in Trimeric Molecular System.

    Science.gov (United States)

    Tsujiuchi, Yutaka; Masumoto, Hiroshi; Goto, Takashi

    2016-04-01

    To elucidate the time evolution of photo reaction of bacteriorhodopsin in glycerol mixed purple membrane at around 196 K under irradiation by red light, a kinetic model was constructed. The change of absorption with irradiation at times of 560 nm and 412 nm was analyzed for the purpose of determining reaction rates of photo reaction of bacteriorhodopsin and its product M intermediate. In this study it is shown that reaction rates of conversion from bacteriorhodopsin to the M intermediate can be explained by a set of linear differential equations. This model analysis concludes that bacteriorhodopsin in which constitutes a trimer unit with other two bacteriorhodopsin molecules changes into M intermediates in the 1.73 of reaction rate, in the initial step, and according to the number of M intermediate in a trimer unit, from three to one, the reaction rate of bacteriorhodopsin into M intermediates smaller as 1.73, 0.80, 0.19 which caused by influence of inter-molecular interaction between bacteriorhodopsin. PMID:27451646

  10. Wire and extended ladder model predict THz oscillations in DNA monomers, dimers and trimers

    CERN Document Server

    Lambropoulos, K; Morphis, A; Tassi, M; Lopp, R; Georgiadis, G; Theodorakou, M; Chatzieleftheriou, M; Simserides, C

    2016-01-01

    We call \\textit{monomer} a B-DNA base pair and study, analytically and numerically, electron or hole oscillations in \\textit{monomers}, \\textit{dimers} and \\textit{trimers}. We employ two Tight Binding (TB) approaches: (I) at the base-pair level, using the on-site energies of the base pairs and the hopping parameters between successive base pairs i.e. \\textit{a wire model}, and (II) at the single-base level, using the on-site energies of the bases and the hopping parameters between neighbouring bases, specifically between (a) two successive bases in the same strand, (b) complementary bases that define a base pair, and (c) diagonally located bases of successive base pairs, i.e. \\textit{an extended ladder model} since it also includes the diagonal hoppings (c). For \\textit{monomers}, with TB II, we predict periodic carrier oscillations with frequency $f \\approx$ 50-550 THz. For \\textit{dimers}, with TB I, we predict periodic carrier oscillations with $f \\approx$ 0.25-100 THz. For \\textit{trimers made of identic...

  11. Advanced environmentally friendly coatings prepared from amine-capped aniline trimer-based waterborne electroactive polyurethane

    International Nuclear Information System (INIS)

    Electroactive waterborne polyurethane (EWPU) containing conjugated segments of electroactive amino-capped aniline trimer (ACAT) unit was successfully prepared and characterized. Iodine-doped EWPU with conductivity 1.2 × 10−6 S cm−1 was detected. The electroactivity of EWPU was evaluated by performing electrochemical cyclic voltammetry studies. It was worth noting that the EWPU coating was found to exhibit enhanced corrosion protection effects on cold-rolled steel (CRS) electrodes as compared to the corresponding non-electroactive waterborne polyurethane (NEWPU) coating based on a series of electrochemical measurements in 3.5 wt% NaCl electrolyte. A possible mechanism for the enhanced corrosion protection ability of the EWPU coatings on the CRS electrode could be interpreted as the redox catalytic capabilities of the aniline trimer units existed in EWPU induce the formation of passive metal oxide layers on the CRS electrode, as further evidenced by SEM and XPS studies. The thermal stability of EWPU was also investigated by thermogravimetric analysis (TGA). Highlights: ► Electroactive waterborne polyurethane (EWPU) was successfully synthesized. ► Electroactivity of EWPU was investigated by electrochemical CV analysis. ► Corrosion protection of EWPU coating was better than NEWPU.

  12. Solution structure of the coiled-coil trimerization domain from lung surfactant protein D

    Energy Technology Data Exchange (ETDEWEB)

    Kovacs, Helena [Bruker BioSpin AG (Switzerland); O' Donoghue, Sean I. [European Molecular Biology Laboratory (Germany); Hoppe, Hans-Juergen [University of Oxford, MRC Immunochemistry Unit (United Kingdom); Comfort, David [University of Oxford, Department of Biochemistry (United Kingdom); Reid, Kenneth B.M. [University of Oxford, MRC Immunochemistry Unit (United Kingdom); Campbell, Iain D. [University of Oxford, Department of Biochemistry (United Kingdom); Nilges, Michael [European Molecular Biology Laboratory (Germany)], E-mail: nilges@pasteur.fr

    2002-10-15

    Surfactant protein D (SP-D) is one of four known protein components of the pulmonary surfactant lining the lung alveoli. It is involved in immune and allergic responses. SP-D occurs as a tetramer of trimers. Trimerization is thought to be initiated by a coiled coil domain. We have determined the solution structure of a 64-residue peptide encompassing the coiled coil domain of human SP-D. As predicted, the domain forms a triple-helical parallel coiled coil. As with all symmetric oligomers, the structure calculation was complicated by the symmetry degeneracy in the NMR spectra. We used the symmetry-ADR (ambiguous distance restraint) structure calculation method to solve the structure. The results demonstrate that the leucine zipper region of SP-D is an autonomously folded domain. The structure is very similar to the independently determined X-ray crystal structure, differing mainly at a single residue, Tyr248. This residue is completely symmetric in the solution structure, and markedly asymmetric in the crystalline phase. This difference may be functionally important, as it affects the orientation of the antigenic surface presented by SP-D.

  13. Trimeric cluster of lithium amidoborane-the smallest unit for the modeling of hydrogen release mechanism.

    Science.gov (United States)

    Pomogaeva, Anna V; Morokuma, Keiji; Timoshkin, Alexey Y

    2016-05-30

    A detailed first-principle DFT M06/6-311++G(d.p) study of dehydrogenation mechanism of trimeric cluster of lithium amidoborane is presented. The first step of the reaction is association of two LiNH2 BH3 molecules in the cluster. The dominant feature of the subsequent reaction pathway is activation of H atom of BH3 group by three Li atoms with formation of unique Li3 H moiety. This Li3 H moiety is destroyed prior to dehydrogenation in favor of formation of a triangular Li2 H moiety, which interacts with protic H atom of NH2 group. As a result of this interaction, Li2 H2 moiety is produced. It features N(-) H(+) H(-) group suited near the middle plane between two Li(+) in the transition state that leads to H2 release. The transition states of association and hydrogen release steps are similar in energy. It is concluded that the trimer, (LiNH2 BH3 )3 , is the smallest cluster that captures the essence of the hydrogen release reaction. © 2016 Wiley Periodicals, Inc. PMID:26854644

  14. Influence of process parameters on the reaction kinetics of the chromium-catalyzed trimerization of ethylene.

    Science.gov (United States)

    Wöhl, Anina; Müller, Wolfgang; Peitz, Stephan; Peulecke, Normen; Aluri, Bhaskar R; Müller, Bernd H; Heller, Detlef; Rosenthal, Uwe; Al-Hazmi, Mohammed H; Mosa, Fuad M

    2010-07-12

    In this paper we report the results of an extensive experimental kinetic study carried out on the novel ethylene trimerization catalyst system, comprising the chromium source [CrCl(3)(thf)(3)] (thf=tetrahydrofuran), a Ph(2)P-N(iPr)-P(Ph)-N(iPr)H (PNPNH) ligand (Ph=phenyl, iPr=isopropyl), and triethylaluminum (AlEt(3)) as activator. It could be shown that the initial activity shows a first-order dependency on the ethylene concentration. Also, a first-order dependency was found for the catalyst concentration. The initial activity follows a typical Arrhenius behavior with an experimentally determined activation energy of 52.6 kJ mol(-1). At elevated temperatures (ca. 80 degrees C), a significant deactivation was observed, which can be tentatively traced back to a ligand rearrangement in the presence of AlEt(3). After a fast initial phase, a pronounced 'kink' in the ethylene-uptake curve is observed, followed by a slow, almost linear, further increase of the total ethylene consumption. The catalyst composition, in particular the ligand/chromium and the cocatalyst/chromium molar ratio, has a strong impact on the catalytic performance of the trimerization of ethylene. PMID:20512824

  15. Evidences of monomer, dimer and trimer of recombinant human cyclophilin A.

    Science.gov (United States)

    Zhang, Xin-Chao; Wang, Wei-Dong; Wang, Jin-Song; Pan, Ji-Cheng; Zou, Guo-Lin

    2011-12-01

    Cyclophilin A (CyPA) is a cytosolic receptor of immunosuppressive drug cyclosporin A (CsA) which possesses peptidyl-prodyl cis/trans isomerase (PPIase) activity. The recombinant human CyPA (rhCyPA) gene has been expressed in E. coli M15. Purification was performed using salting-out, as well as Sephacryl S-100 and DEAE-Sepharose CL-6B column chromatography. The molecular weight is about 18 kDa, confirmed by SDS-PAGE and mass spectrum. The results of Native-PAGE and immunoblotting showed the existence of three bands, which agreed well with the gel filtration results. The molecular mass of the three bands determined via CTAB gel electrophoresis and SDS-PAGE (rhCyPA cross-linked with glutaraldehyde) was 18 kDa, 36 kDa and 54 kDa respectively. Further more, the native rhCyPA and the cross-linked rhCyPA had the similar chromatographic behavior in gel filtration. All of the evidences above suggest that rhCyPA exists in forms of monomer, dimer and trimer. Moreover, we observed that even at low protein concentrations CyPA largely occurs as a dimer in solution, and enzyme kinetic parameters showed that activity of dimer was much higher than monomer or trimer, which probably have some biological significances. PMID:21728990

  16. An N-terminal glycine-rich sequence contributes to retrovirus trimer of hairpins stability

    International Nuclear Information System (INIS)

    Retroviral transmembrane proteins (TMs) contain a glycine-rich segment linking the N-terminal fusion peptide and coiled coil core. Previously, we reported that the glycine-rich segment (Met-326-Ser-337) of the human T-cell leukemia virus type 1 (HTLV-1) TM, gp21, is a determinant of membrane fusion function [K.A. Wilson, S. Baer, A.L. Maerz, M. Alizon, P. Poumbourios, The conserved glycine-rich segment linking the N-terminal fusion peptide to the coiled coil of human T-cell leukemia virus type 1 transmembrane glycoprotein gp21 is a determinant of membrane fusion function, J. Virol. 79 (2005) 4533-4539]. Here we show that the reduced fusion activity of an I334A mutant correlated with a decrease in stability of the gp21 trimer of hairpins conformation, in the context of a maltose-binding protein-gp21 chimera. The stabilizing influence of Ile-334 required the C-terminal membrane-proximal sequence Trp-431-Ser-436. Proline substitution of four of five Gly residues altered gp21 trimer of hairpins stability. Our data indicate that flexibility within and hydrophobic interactions mediated by this region are determinants of gp21 stability and membrane fusion function

  17. Solution structure of the coiled-coil trimerization domain from lung surfactant protein D

    International Nuclear Information System (INIS)

    Surfactant protein D (SP-D) is one of four known protein components of the pulmonary surfactant lining the lung alveoli. It is involved in immune and allergic responses. SP-D occurs as a tetramer of trimers. Trimerization is thought to be initiated by a coiled coil domain. We have determined the solution structure of a 64-residue peptide encompassing the coiled coil domain of human SP-D. As predicted, the domain forms a triple-helical parallel coiled coil. As with all symmetric oligomers, the structure calculation was complicated by the symmetry degeneracy in the NMR spectra. We used the symmetry-ADR (ambiguous distance restraint) structure calculation method to solve the structure. The results demonstrate that the leucine zipper region of SP-D is an autonomously folded domain. The structure is very similar to the independently determined X-ray crystal structure, differing mainly at a single residue, Tyr248. This residue is completely symmetric in the solution structure, and markedly asymmetric in the crystalline phase. This difference may be functionally important, as it affects the orientation of the antigenic surface presented by SP-D

  18. A procyanidin type A trimer from cinnamon extract attenuates glial cell swelling and the reduction in glutamate uptake following ischemic injury in vitro

    Science.gov (United States)

    Dietary polyphenols exert neuroprotective effects in ischemic injury. The protective effects of a procyanidin type A trimer (trimer 1) isolated from a water soluble cinnamon extract (CE) were investigated on key features of ischemic injury including cell swelling, increased free radical production, ...

  19. Intramolecular trimerization, a novel strategy for making multispecific antibodies with controlled orientation of the antigen binding domains

    DEFF Research Database (Denmark)

    Álvarez-Cienfuegos, Ana; Alanes, Natalia Nuñez del Prado; Compte, Marta; Cuesta, Àngel M; Blanco-Toribio, Ana; Harwood, Seandean Lykke; Villate, Maider; Merino, Nekane; Bonet, Jaume; Navarro, Rocio; Muñoz-Briones, Clara; Sørensen, Karen Marie Juul; Mølgaard, Kasper; Oliva, Baldomero; Blanco, Francisco J; Álvarez-Vallina, Luis

    2016-01-01

    Here, we describe a new strategy that allows the rapid and efficient engineering of mono and multispecific trivalent antibodies. By fusing single-domain antibodies from camelid heavy-chain-only immunoglobulins (VHHs) to the N-terminus of a human collagen XVIII trimerization domain (TIEXVIII) we p...

  20. Experiment and theory elucidate the multichannel predissociation dynamics of the HCl trimer: breaking up is hard to do.

    Science.gov (United States)

    Mancini, John S; Samanta, Amit K; Bowman, Joel M; Reisler, Hanna

    2014-09-18

    The breaking of hydrogen bonds in molecular systems has profound effects on liquids, e.g., water, biomolecules, e.g., DNA, etc., and so it is no exaggeration to assert the importance of these bonds to living systems. However, despite years of extensive research on hydrogen bonds, many of the details of how these bonds break and the corresponding energy redistribution processes remain poorly understood. Here we report extensive experimental and theoretical insights into the breakup of two or three hydrogen bonds in the dissociation of a paradigm system of a hydrogen-bonded network, the ring HCl trimer. Experimental state-to-state vibrational predissociation dynamics of the trimer following vibrational excitation were studied by using velocity map imaging and resonance-enhanced multiphoton ionization, providing dissociation energies and product state distributions for the trimer's breakup into three separate monomers or into dimer + monomer. Accompanying the experiments are high-level calculations using diffusion Monte Carlo and quasiclassical simulations, whose results validate the experimental ones and further elucidate energy distributions in the products. The calculations make use of a new, highly accurate potential energy surface. Simulations indicate that the dissociation mechanism requires the excitation to first relax into low-frequency motions of the trimer, resulting in the breaking of a single hydrogen bond. This allows the system to explore a critical van der Waals minimum region from which dissociation occurs readily to monomer + dimer. PMID:24559271

  1. Conformational divergence in the HA-33/HA-17 trimer of serotype C and D botulinum toxin complex.

    Science.gov (United States)

    Sagane, Yoshimasa; Hayashi, Shintaro; Akiyama, Tomonori; Matsumoto, Takashi; Hasegawa, Kimiko; Yamano, Akihito; Suzuki, Tomonori; Niwa, Koichi; Watanabe, Toshihiro; Yajima, Shunsuke

    2016-08-01

    Clostridium botulinum produces a large toxin complex (L-TC) comprising botulinum neurotoxin associated with auxiliary nontoxic proteins. A complex of 33- and 17-kDa hemagglutinins (an HA-33/HA-17 trimer) enhances L-TC transport across the intestinal epithelial cell layer via binding HA-33 to a sugar on the cell surface. At least two subtypes of serotype C/D HA-33 exhibit differing preferences for the sugars sialic acid and galactose. Here, we compared the three-dimensional structures of the galactose-binding HA-33 and HA-33/HA-17 trimers produced by the C-Yoichi strain. Comparisons of serotype C/D HA-33 sequences reveal a variable region with relatively low sequence similarity across the C. botulinum strains; the variability of this region may influence the manner of sugar-recognition by HA-33. Crystal structures of sialic acid- and galactose-binding HA-33 are broadly similar in appearance. However, small-angle X-ray scattering revealed distinct solution structures for HA-33/HA-17 trimers. A structural change in the C-terminal variable region of HA-33 might cause a dramatic shift in the conformation and sugar-recognition mode of HA-33/HA-17 trimer. PMID:27237978

  2. Triphenylene discotic liquid crystal trimers synthesized by Co2(CO8-catalyzed terminal alkyne [2 + 2 + 2] cycloaddition

    Directory of Open Access Journals (Sweden)

    Bin Han

    2013-12-01

    Full Text Available The synthesis of star-shaped discotic liquid crystal trimers using Co2(CO8-catalyzed terminal alkyne [2 + 2 + 2] cycloaddition reaction is reported. The trimers consist of three triphenylene discotic units linked to a central 1,2,4-trisubstituted benzene ring via flexible spacers. The trimers were synthesized in the yields up to 70% by mixing the monomers with 10 mol % of Co2(CO8 as the catalyst in refluxing 1,4-dioxane. The liquid crystalline properties were investigated by using polarizing optical microscopy (POM, differential scanning calorimetry (DSC and X-ray diffraction (XRD. Trimer 4 with an ester connecting group and a longer spacer exhibited a rectangular columnar mesophase, while 5b and 5c possessing an ether linkage and a shorter spacer display a hexagonal columnar mesophase. The connecting functional group and the length of the flexible spacer between the central benzene ring and the triphenylene units have pivotal influence on the mesomorphism.

  3. Prism-C2n carbon dimer, trimer, and nano-sheets: A quantum chemical study

    Science.gov (United States)

    Ohno, Koichi; Satoh, Hiroko; Iwamoto, Takeaki

    2015-07-01

    Quantum chemical calculations have predicted the existence of a new carbon family with double-layered structures formed by arranging prism-C2n (n = 6, 8, and 12) units. Theoretical explorations of potential energy surfaces suggest the lowest barriers of the reaction channels to be ca. 30 kJ mol-1 for a D2h prism-C16 dimer and a D3h prism-C24 trimer. Geometry optimizations under periodic boundary conditions yield some prism-C2n sheets composed of CC single bonds of ca. 0.15-0.16 nm. The relative energies per one atom with respect to graphene are 90-160 kJ mol-1. Van der Waals thickness is estimated to be ca. 0.5 nm.

  4. Water adsorption on the Be(0001) surface:from monomer to trimer adsorption

    Institute of Scientific and Technical Information of China (English)

    Ning Hua; Tao Xiang-Ming; Tan Ming-Qiu

    2012-01-01

    In this paper,the density functional theory has been used to perform a comparative theoretical study of water monomer,dimer,trimer,and bilayer adsorptions on the Be(0001) surface. In our calculations,the adsorbed water molecules are energetically favoured adsorbed on the atop sites,and the dimer adsorption is found to be the most stable with a peak adsorption energy of ~ 437 meV.Further analyses have revealed that the essential bonding interaction between the water monomer and the metal substrate is the hybridization of the water 3a1-like molecular orbital with the (s,pz) orbitals of the surface beryllium atoms.While in the case of the water dimer adsorption,the lb1-like orbital of the H2O molecule plays a dominant role.

  5. Manifestation of Universality in the Asymmetric Helium Trimer and in the Halo Nucleus $^{22}$C

    CERN Document Server

    Gridnev, Dmitry K

    2016-01-01

    We prove that the corner angle distributions in the bound three-body system AAB, which consists of two particles of type A and one particle of type B, approach universal form if the pair AA has a virtual state at zero energy and the binding energy of AAB goes to zero. We derive explicit expressions for the universal corner angle distributions in terms of elementary functions, which depend solely on the mass ratio m(A)/m(B) and do not depend on pair interactions. On the basis of experimental data and calculations we demonstrate that such systems as the asymmetric Helium trimer $^3$He$^4$He$_2$ and the halo nucleus $^{22}$C exhibit universal features. Thus our result establishes an interesting link between atomic and nuclear physics through the few-body universality.

  6. Ionization dynamics of the water trimer: A direct ab initio MD study

    Energy Technology Data Exchange (ETDEWEB)

    Tachikawa, Hiroto, E-mail: hiroto@eng.hokudai.ac.jp [Division of Materials Chemistry, Graduate School of Engineering, Hokkaido University, Kita-ku, Sapporo 060-8628 (Japan); Takada, Tomoya [Department of Material Chemistry, Asahikawa National College of Technology, Syunkodai, Asahikawa 071-8142 (Japan)

    2013-03-29

    Highlights: ► We calculated ionization dynamics of water trimer. ► Direct ab initio molecular dynamics (MD) method is applied. ► Proton transfer dynamics were discussed. ► The proton transfer process calculated are well reproduced in recent experiments. - Abstract: Ionization dynamics of the cyclic water trimer (H{sub 2}O){sub 3} have been investigated by means of direct ab initio molecular dynamics (AIMD) method. Two reaction channels, complex formation and OH dissociation, were found following the ionization of (H{sub 2}O){sub 3}. In both channels, first, a proton was rapidly transferred from H{sub 2}O{sup +} to H{sub 2}O (time scale is ∼15 fs after the ionization). In complex channel, an ion–radical contact pair (H{sub 3}O{sup +}–OH) solvated by the third water molecule was formed as a long-lived H{sub 3}O{sup +}(OH)H{sub 2}O complex. In OH dissociation channel, the second proton transfer further takes place from H{sub 3}O{sup +}(OH) to H{sub 2}O (time scale is 50–100 fs) and the OH radical is separated from the H{sub 3}O{sup +}. At the same time, the OH dissociation takes place when the excess energy is efficiently transferred into the kinetic energy of OH radical. The OH dissociation channel is significantly minor, and almost all product channels were the complex formation. The reaction mechanism was discussed on the basis of theoretical results.

  7. A systematic study of electron or hole transfer along DNA dimers, trimers and polymers

    International Nuclear Information System (INIS)

    Highlights: • We systematically study carrier transfer along DNA dimers, trimers and polymers. • We define max transfer percentage, pure max transfer rate, pure mean transfer rate. • For exponential (power-law) fit, the inverse decay length β (exponent η) is computed. • The results are compared with theoretical and experimental works. • The method assesses the extent a specific DNA segment can serve for charge transfer. - Abstract: A systematic study of carrier transfer along DNA dimers, trimers and polymers including poly(dG)–poly(dC), poly(dA)–poly(dT), GCGCGC…, ATATAT… is presented allowing to determine the spatiotemporal evolution of electrons or holes along a N base-pair DNA segment. Physical quantities are defined including maximum transfer percentage p and pure maximum transfer rate p/T when a period T is defined; pure mean transfer rate k and speed u=kd, where d is the charge transfer distance. The inverse decay length β for the exponential fit k=k0exp(-βd) and the exponent η for the power-law fit k=k0′N-η are computed. β≈ 0.2–2 Å−1, k0 is usually 10−2–10−1 PHz, generally ≈10−4–10 PHz. η≈1.7–17, k0′ is usually 10−2–10−1 PHz, generally ≈10−4–103 PHz. The results are compared with theoretical and experimental works. This method allows to assess the extent at which a specific DNA segment can serve for charge transfer

  8. pp-GalNAc-T13 induces high metastatic potential of murine Lewis lung cancer by generating trimeric Tn antigen

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Yasuyuki; Zhang, Qing [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Akita, Kaoru; Nakada, Hiroshi [Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555 (Japan); Hamamura, Kazunori; Tokuda, Noriyo [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Tsuchida, Akiko [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Noguchi Institute, 1-8-1 Kaga, Itabashi, Tokyo 173-0003 (Japan); Matsubara, Takeshi; Hori, Tomoko; Okajima, Tetsuya [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Furukawa, Keiko [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto-cho, Kasugai 487-8501 (Japan); Urano, Takeshi [Department of Biochemistry, Shimane University School of Medicine, Izumo 693-8501 (Japan); Furukawa, Koichi, E-mail: koichi@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan)

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer ppGalNAc-T13 was up-regulated in high metastatic sublines of Lewis lung cancer. Black-Right-Pointing-Pointer ppGalNAc-T13 expression enhanced cell invasion activity in low metastatic sublines. Black-Right-Pointing-Pointer Trimeric Tn antigen was induced in the transfectant cells of ppGalNAc-T13 cDNA. Black-Right-Pointing-Pointer A major protein carrying trimeric Tn structure was identified as Syndecan-1. Black-Right-Pointing-Pointer Silencing of ppGalNAc-T13 resulted in the reduction of invasion and of metastasis.. -- Abstract: In order to analyze the mechanisms for cancer metastasis, high metastatic sublines (H7-A, H7-Lu, H7-O, C4-sc, and C4-ly) were obtained by repeated injection of mouse Lewis lung cancer sublines H7 and C4 into C57BL/6 mice. These sublines exhibited increased proliferation and invasion activity in vitro. Ganglioside profiles exhibited lower expression of GM1 in high metastatic sublines than the parent lines. Then, we established GM1-Si-1 and GM1-Si-2 by stable silencing of GM1 synthase in H7 cells. These GM1-knockdown clones exhibited increased proliferation and invasion. Then, we explored genes that markedly altered in the expression levels by DNA microarray in the combination of C4 vs. C4-ly or H7 vs. H7 (GM1-Si). Consequently, pp-GalNAc-T13 gene was identified as up-regulated genes in the high metastatic sublines. Stable transfection of pp-GalNAc-T13 cDNA into C4 (T13-TF) resulted in increased invasion and motility. Then, immunoblotting and flow cytometry using various antibodies and lectins were performed. Only anti-trimeric Tn antibody (mAb MLS128), showed increased expression levels of trimeric Tn antigen in T13-TF clones. Moreover, immunoprecipitation/immunoblotting was performed by mAb MLS128, leading to the identification of an 80 kDa band carrying trimeric Tn antigen, i.e. Syndecan-1. Stable silencing of endogenous pp-GalNAc-T13 in C4-sc (T13-KD) revealed that primary tumors generated by

  9. pp-GalNAc-T13 induces high metastatic potential of murine Lewis lung cancer by generating trimeric Tn antigen

    International Nuclear Information System (INIS)

    Highlights: ► ppGalNAc-T13 was up-regulated in high metastatic sublines of Lewis lung cancer. ► ppGalNAc-T13 expression enhanced cell invasion activity in low metastatic sublines. ► Trimeric Tn antigen was induced in the transfectant cells of ppGalNAc-T13 cDNA. ► A major protein carrying trimeric Tn structure was identified as Syndecan-1. ► Silencing of ppGalNAc-T13 resulted in the reduction of invasion and of metastasis.. -- Abstract: In order to analyze the mechanisms for cancer metastasis, high metastatic sublines (H7-A, H7-Lu, H7-O, C4-sc, and C4-ly) were obtained by repeated injection of mouse Lewis lung cancer sublines H7 and C4 into C57BL/6 mice. These sublines exhibited increased proliferation and invasion activity in vitro. Ganglioside profiles exhibited lower expression of GM1 in high metastatic sublines than the parent lines. Then, we established GM1-Si-1 and GM1-Si-2 by stable silencing of GM1 synthase in H7 cells. These GM1-knockdown clones exhibited increased proliferation and invasion. Then, we explored genes that markedly altered in the expression levels by DNA microarray in the combination of C4 vs. C4-ly or H7 vs. H7 (GM1-Si). Consequently, pp-GalNAc-T13 gene was identified as up-regulated genes in the high metastatic sublines. Stable transfection of pp-GalNAc-T13 cDNA into C4 (T13-TF) resulted in increased invasion and motility. Then, immunoblotting and flow cytometry using various antibodies and lectins were performed. Only anti-trimeric Tn antibody (mAb MLS128), showed increased expression levels of trimeric Tn antigen in T13-TF clones. Moreover, immunoprecipitation/immunoblotting was performed by mAb MLS128, leading to the identification of an 80 kDa band carrying trimeric Tn antigen, i.e. Syndecan-1. Stable silencing of endogenous pp-GalNAc-T13 in C4-sc (T13-KD) revealed that primary tumors generated by subcutaneous injection of T13-KD clones showed lower coalescence to fascia and peritoneum, and significantly reduced lung

  10. Electronic transitions of guanine tautomers, their stacked dimers, trimers and sodium complexes

    Science.gov (United States)

    Kushwaha, P. S.; Kumar, Anil; Mishra, P. C.

    2004-02-01

    Planar and nonplanar geometries of the keto-N9H and keto-N7H tautomers of the guanine base of DNA as well as the hydrogen bonded complexes of these species with three water molecules each were optimized using the density functional theory at the B3LYP/6-31G ∗ ∗ level. Geometries of the isolated bases were also optimized using the ab initio approach at the MP2/6-31G ∗ ∗ level. The isolated keto-N9H and keto-N7H tautomers as well as their hydrogen bonded complexes with three water molecules each were solvated in bulk water employing the polarized continuum model (PCM) of the self-consistent reaction field theory (SCRF). Stacked dimers and trimers of both the tautomers of guanine were generated by placing the planar forms of the species at a fixed distance of 3.5 Å from the neighboring one and rotating one molecule with respect to the other by 110° for the keto-N9H form and 90° for the keto-N7H form which corresponded to total energy minima at the B3LYP/6-31G ∗ ∗ level. Geometry optimization for the cation of the monomer of guanine was performed at the same level of theory, and its solvation in bulk water was treated using the PCM model of the SCRF theory. The geometries of complexes of the two tautomers of guanine with a Na + ion each were optimized at the B3LYP/6-31G ∗ ∗ level, and the Na + ion is predicted to bind with the keto-N9H tautomer preferentially. While the complex of the keto-N7H form of guanine with three water molecules in gas phase is slightly more stable than the corresponding complex of the keto-N9H form of guanine, the reverse is true in bulk water. Stacking interactions enhance the relative stability of the keto-N9H tautomer over that of the keto-N7H tautomer, suggesting that in bulk solutions, the former would be dominant. Electronic spectra of the isolated tautomers of guanine, those of their complexes with three water molecules each, the (keto-n9h and keto-n7h) cation of guanine, the complexes of the tautomers with a Na + ion

  11. A computational study of dimers and trimers of nitrosyl hydride: Blue shift of NH bonds that are involved in H-bond and orthogonal interactions

    International Nuclear Information System (INIS)

    Ab initio calculations at MP2/aug-cc-pVTZ level were used to analyze the interactions between nitrosyl hydride (HNO) dimers and trimers. The structures obtained have been analyzed with the Atoms in Molecules (AIMs) and Natural Bond Orbital (NBO) methodologies. Four minima were located on the potential energy surface of the dimers. Nine different structures have been obtained for the trimers. Three types of interactions are observed, NH···N and NH···O hydrogen bonds and orthogonal interaction between the lone pair of the oxygen with the electron-deficient region of the nitrogen atom. Stabilization energies of dimers and trimers including BSSE and ZPE are in the range 4-8 kJ mol-1 and 12-19 kJ mol-1, respectively. Blue shift of NH bond upon complex formation in the ranges between 30-80 and 14,114 cm-1 is predicted for dimers and trimers, respectively.

  12. Hydrolyzable tannins of tamaricaceous plants. V. Structures of monomeric-trimeric tannins and cytotoxicity of macrocyclic-type tannins isolated from Tamarix nilotica (1).

    Science.gov (United States)

    Orabi, Mohamed A A; Taniguchi, Shoko; Sakagami, Hiroshi; Yoshimura, Morio; Yoshida, Takashi; Hatano, Tsutomu

    2013-05-24

    Three new ellagitannin monomers, nilotinins M5-M7 (1-3), a dimer, nilotinin D10 (4), and a trimer, nilotinin T1 (5), together with three known dimers, hirtellin D (7) and tamarixinins B (8) and C (9), and a trimer, hirtellin T2 (6), were isolated from Tamarix nilotica dried leaves. The structures of the tannins were elucidated by intensive spectroscopic methods and chemical conversions into known tannins. The new trimer (5) is a unique macrocyclic type whose monomeric units are linked together by an isodehydrodigalloyl and two dehydrodigalloyl moieties. Additionally, dimeric and trimeric macrocyclic-type tannins isolated from T. nilotica in this study were assessed for possible cytotoxic activity against four human tumor cell lines. Tumor-selective cytotoxicities of the tested compounds were higher than those of synthetic and natural potent cytotoxic compounds, including polyphenols, and comparable with those of 5-fluorouracil and melphalan. PMID:23675651

  13. Kin28 Is Found within TFIIH and a Kin28-Ccl1-Tfb3 Trimer Complex with Differential Sensitivities to T-Loop Phosphorylation

    OpenAIRE

    Keogh, Michael-Christopher; Cho, Eun-Jung; Podolny, Vladimir; Buratowski, Stephen

    2002-01-01

    Basal transcription factor TFIIH phosphorylates the RNA polymerase II (RNApII) carboxy-terminal domain (CTD) within the transcription initiation complex. The catalytic kinase subunit of TFIIH is a member of the cyclin-dependent kinase (Cdk) family, designated Kin28 in Saccharomyces cerevisiae and Cdk7 in higher eukaryotes. Together with TFIIH subunits cyclin H and Mat1, Cdk7 kinase is also found in a trimer complex known as Cdk activating kinase (CAK). A yeast trimer complex has not previousl...

  14. Energy transfer dynamics in trimers and aggregates of light-harvesting complex II probed by 2D electronic spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Enriquez, Miriam M.; Zhang, Cheng; Tan, Howe-Siang, E-mail: howesiang@ntu.edu.sg [Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore); Akhtar, Parveen; Garab, Győző; Lambrev, Petar H., E-mail: lambrev@brc.hu [Institute of Plant Biology, Biological Research Centre, Hungarian Academy of Sciences, P.O. Box 521, H-6701 Szeged (Hungary)

    2015-06-07

    The pathways and dynamics of excitation energy transfer between the chlorophyll (Chl) domains in solubilized trimeric and aggregated light-harvesting complex II (LHCII) are examined using two-dimensional electronic spectroscopy (2DES). The LHCII trimers and aggregates exhibit the unquenched and quenched excitonic states of Chl a, respectively. 2DES allows direct correlation of excitation and emission energies of coupled states over population time delays, hence enabling mapping of the energy flow between Chls. By the excitation of the entire Chl b Q{sub y} band, energy transfer from Chl b to Chl a states is monitored in the LHCII trimers and aggregates. Global analysis of the two-dimensional (2D) spectra reveals that energy transfer from Chl b to Chl a occurs on fast and slow time scales of 240–270 fs and 2.8 ps for both forms of LHCII. 2D decay-associated spectra resulting from the global analysis identify the correlation between Chl states involved in the energy transfer and decay at a given lifetime. The contribution of singlet–singlet annihilation on the kinetics of Chl energy transfer and decay is also modelled and discussed. The results show a marked change in the energy transfer kinetics in the time range of a few picoseconds. Owing to slow energy equilibration processes, long-lived intermediate Chl a states are present in solubilized trimers, while in aggregates, the population decay of these excited states is significantly accelerated, suggesting that, overall, the energy transfer within the LHCII complexes is faster in the aggregated state.

  15. Trimeric Autotransporters of Haemophilus parasuis: Generation of an Extensive Passenger Domain Repertoire Specific for Pathogenic Strains▿ †

    OpenAIRE

    Pina, Sonia; Olvera, Alex; Barceló, Anna; Bensaid, Albert

    2008-01-01

    Haemophilus parasuis is the agent responsible for causing Glässer's disease, but little is known about the pathogenic determinants of this major pig disease. Here we describe, for the pathogenic strain Nagasaki, the molecular characterization of 13 trimeric autotransporters as assessed by the presence of YadA C-terminal translocator domains which were classified into three groups. All passenger domains possess motifs and repeats characteristic of adhesins, hemagglutinins, and invasins with va...

  16. Energy transfer dynamics in trimers and aggregates of light-harvesting complex II probed by 2D electronic spectroscopy

    International Nuclear Information System (INIS)

    The pathways and dynamics of excitation energy transfer between the chlorophyll (Chl) domains in solubilized trimeric and aggregated light-harvesting complex II (LHCII) are examined using two-dimensional electronic spectroscopy (2DES). The LHCII trimers and aggregates exhibit the unquenched and quenched excitonic states of Chl a, respectively. 2DES allows direct correlation of excitation and emission energies of coupled states over population time delays, hence enabling mapping of the energy flow between Chls. By the excitation of the entire Chl b Qy band, energy transfer from Chl b to Chl a states is monitored in the LHCII trimers and aggregates. Global analysis of the two-dimensional (2D) spectra reveals that energy transfer from Chl b to Chl a occurs on fast and slow time scales of 240–270 fs and 2.8 ps for both forms of LHCII. 2D decay-associated spectra resulting from the global analysis identify the correlation between Chl states involved in the energy transfer and decay at a given lifetime. The contribution of singlet–singlet annihilation on the kinetics of Chl energy transfer and decay is also modelled and discussed. The results show a marked change in the energy transfer kinetics in the time range of a few picoseconds. Owing to slow energy equilibration processes, long-lived intermediate Chl a states are present in solubilized trimers, while in aggregates, the population decay of these excited states is significantly accelerated, suggesting that, overall, the energy transfer within the LHCII complexes is faster in the aggregated state

  17. An Acinetobacter trimeric autotransporter adhesin reaped from cells exhibits its nonspecific stickiness via a highly stable 3D structure

    OpenAIRE

    Shogo Yoshimoto; Hajime Nakatani; Keita Iwasaki; Katsutoshi Hori

    2016-01-01

    Trimeric autotransporter adhesins (TAAs), cell surface proteins of Gram-negative bacteria, mediate bacterial adhesion to host cells and extracellular matrix proteins. However, AtaA, a TAA in the nonpathogenic Acinetobacter sp. strain Tol 5, shows nonspecific, high adhesiveness to abiotic material surfaces as well as to biotic surfaces. AtaA is a homotrimer of polypeptides comprising 3,630 amino acids and forms long nanofibers; therefore, it is too large and structurally complex to be produced...

  18. Crystal structures of the trimeric human immunodeficiency virus type 1 matrix protein: implications for membrane association and assembly.

    OpenAIRE

    Hill, C. P.; Worthylake, D; Bancroft, D P; Christensen, A. M.; Sundquist, W. I.

    1996-01-01

    The human immunodeficiency virus type 1 (HIV-1) matrix protein forms a structural shell associated with the inner viral membrane and performs other essential functions throughout the viral life cycle. The crystal structure of the HIV-1 matrix protein, determined at 2.3 angstrom resolution, reveals that individual matrix molecules are composed of five major helices capped by a three-stranded mixed beta-sheet. Unexpectedly, the protein assembles into a trimer in three different crystal lattices...

  19. Enhancement of antiviral activity of collectin trimers through cross-linking and mutagenesis of the carbohydrate recognition domain

    DEFF Research Database (Denmark)

    White, Mitchell R; Boland, Patrick; Tecle, Tesfaldet; Gantz, Donald; Sørensen, Grith Lykke; Tornøe, Ida; Holmskov, Uffe; McDonald, Barbara; Crouch, Erika C; Hartshorn, Kevan L

    2010-01-01

    Surfactant protein D (SP-D) plays important roles in innate defense against respiratory viruses [including influenza A viruses (IAVs)]. Truncated trimers composed of its neck and carbohydrate recognition domains (NCRDs) bind various ligands; however, they have minimal inhibitory activity for IAV......, complementary strategies, namely cross-linking of NCRDs through various means and mutagenesis of CRD residues to increase viral binding. These findings may be relevant for antiviral therapy....

  20. Evidence for covalently cross-linked dimers and trimers of enzyme I of the Escherichia coli phosphotransferase system.

    OpenAIRE

    Grenier, F C; Reizer, J; Waygood, E B; Saier, M H

    1985-01-01

    Enzyme I of the bacterial phosphotransferase system catalyzes transfer of the phosphoryl moiety from phosphoenolpyruvate to both of the heat-stable phosphoryl carrier proteins of the phosphotransferase system, HPr and FPr. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high-pressure liquid chromatography, we demonstrated the existence of covalently cross-linked enzyme I dimers and trimers. Enzyme I exchange assays and phosphorylation experiments with [32P]phosphoenolpyruv...

  1. Fractional Mott insulator-to-superfluid transition of Bose-Hubbard model in a trimerized Kagomé optical lattice.

    Science.gov (United States)

    Chen, Qi-Hui; Li, Peng; Su, Haibin

    2016-06-29

    By generalizing the traditional single-site strong coupling expansion approach to a cluster one, we study the zero-temperature phase diagram of bosonic atoms in a trimerized Kagomé optical lattice. Some new features are present in this system. Due to the strong intra-trimer hopping interaction, there will be a new Mott insulator (MI), which is by definition incompressible but with a fractional filling per trimer. This is different from the traditional MI, which has an integral filling and originates only from the repulsive interaction between particles. We investigate the MI-to-superfluid transition and the nature of the fractional MI by calculating the critical exponents of phase transitions and the low-lying energy excitation spectra of quasiparticles (quasihole). We will show how the low-energy properties of this system can be understood qualitatively as a Bose-Hubbard model in triangular lattice from the point of view of the cluster strong coupling expansion. We also discuss how our results are related to experiment by studying the Bragg spectroscopy. PMID:27165440

  2. Quantifying Dimer and Trimer Formation by Tri-n-butyl Phosphates in n-Dodecane: Molecular Dynamics Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Vo, Quynh N.; Dang, Liem X.; Nilsson, Mikael; Nguyen, Hung D.

    2016-07-21

    Tri-n-butyl phosphate (TBP), a representative of neutral organophosphorous ligands, is an important extractant used in solvent extraction process for the recovery of uranium and plutonium from spent nuclear fuel. Microscopic pictures of TBP isomerism and its behavior in n-dodecane diluent were investigated utilizing MD simulations with previously optimized force field parameters for TBP and n-dodecane. Potential Mean Force (PMF) calculations on a single TBP molecule show seven probable TBP isomers. Radial Distribution Functions (RDF) of TBP suggests the existence of TBP trimers at high TBP concentrations in addition to dimers. 2D PMF calculations were performed to determine the angle and distance criteria for TBP trimers. The dimerization and trimerization constants of TBP in n-dodecane were obtained and match our own experimental values using FTIR technique. The new insights into the conformational behaviors of TBP molecule as a monomer and as part of an aggregate could greatly aid the understanding of the complexation between TBP and metal ions in solvent extraction system. The U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences funded the work performed by LXD.

  3. Traveling waves in trimer granular lattice I: Bifurcation structure of traveling waves in the unit-cell model

    Science.gov (United States)

    Jayaprakash, K. R.; Shiffer, A.; Starosvetsky, Y.

    2016-09-01

    Present paper is the first one in the series devoted to the dynamics of traveling waves emerging in the uncompressed, tri-atomic granular crystals. This work is primarily concerned with the dynamics of one-dimensional periodic granular trimer (tri-atomic) chains in the state of acoustic vacuum. Each unit cell consists of three spherical particles of different masses subject to periodic boundary conditions. Hertzian interaction law governs the mutual interaction of these particles. Under the assumption of zero pre-compression, this interaction is modeled as purely nonlinear, which means the absence of linear force component. The dynamics of such chains is governed by the two system parameters that scale the mass ratios between the particles of the unit cell. Such a system supports two different classes of periodic solutions namely the traveling and standing waves. The primary objective of the present study is the numerical analysis of the bifurcation structure of these solutions with emphasis on the dynamics of traveling waves. In fact, understanding of the bifurcation structure of the traveling wave solutions emerging in the unit-cell granular trimer is rather important and can shed light on the more complex nonlinear wave phenomena emerging in semi-infinite trimer chains.

  4. Relation between cooperative effects in cyclic water, methanol/water, and methanol trimers and hydrogen bonds in methanol/water, ethanol/water, and dimethylether/water heterodimers

    Science.gov (United States)

    Masella, Michel; Flament, Jean Pierre

    1998-05-01

    Ab initio calculations at the MP2 level have been performed on water, methanol/water, ethanol/water, and dimethylether/water dimers and on water, methanol/water, and methanol cyclic trimers. Several properties of their hydrogen bonds have been investigated, such as interoxygen distances, O-H bond lengths, binding energies, electronic densities at hydrogen bond (HB) critical points and OH stretch vibrational frequencies. Results exhibit HB enhancements for dimers where the acceptor molecule corresponds to water (HDA dimers) as compared to dimers where the donor is water (HDD dimers). In particular, HB reinforcement depends on the number of alkyl groups bonded to the donor oxygen. For trimers, a comparison among their HB properties and those of dimers shows that HB reinforcements (as compared to isolated dimers) occurring in trimers correlate with HB reinforcements observed in (HDA dimers (as compared to (HDDs). In particular, HB properties of the cyclic water trimer are close to those of alcohol/water HDA dimers, and for the methanol cyclic trimer to that of the dimethylether/water HDA dimer. All of these results agree with an orbital interpretation of hydrogen bonding in terms of charge transfer from donor lone pairs to acceptor antibond σOH*, even if all of the HB properties in cyclic trimers may not be explained from this approach.

  5. Linear Trimeric Hafnium Clusters in Hf0.86(1I3

    Directory of Open Access Journals (Sweden)

    Jan Beekhuizen

    2011-05-01

    Full Text Available The reduction of hafnium tetraiodide, HfI4, with aluminum at 600 °C or 850 °C in the presence of a NaI flux resulted in black single crystals of Hf0.86(1I3. This composition corresponds well to the upper end of the non-stoichiometry range 0.89 ≤ x ≤ 1.00 previously reported for HfxI3. The crystal structure (a = 1250.3(2, c = 1999.6(3 pm, R-3m, Z = 18 is made up of hexagonal closest packed layers of iodide ions. One third of the octahedral holes would be filled as in TiI3 or ZrI3 if it were Hf1.00I3. In Hf0.86(1I3, one out of six octahedral holes along [001] are, however, only occupied by 16%. In contrast to TiI3-I and ZrI3, one striking structural feature is in the formation of linear hafnium trimers with identical Hf―Hf distances of 318.3(2 pm rather than the formation of dimers. These may be associated with Hf―Hf bonding although only 2.64 electrons are available for one Hf5.16I18 column.

  6. Clustering of OB-fold domains of the partner protease complexed with trimeric stomatin from Thermococcales.

    Science.gov (United States)

    Yokoyama, Hideshi; Matsui, Eriko; Hiramoto, Kana; Forterre, Patrick; Matsui, Ikuo

    2013-07-01

    The C-terminal soluble domain of stomatin operon partner protein (STOPP) of the hyperthermophilic archaeon Pyrococcus horikoshii has an oligonucleotide binding-fold (OB-fold). STOPP lacks the conserved surface residues necessary for binding to DNA/RNA. A tryptophan (W) residue is conserved instead at the molecular surface. Solvent-accessible W residues are often found at interfaces of protein-protein complexes, which suggested the possibility of self-assembling of STOPP. Protein-protein interactions among the C-terminal soluble domains of STOPP PH1510 (1510-C) were then analyzed by chemical linking and blue native polyacrylamide gel electrophoresis (BN-PAGE) methods. These results suggest that the soluble domains of STOPP could assemble into homo-oligomers. Since hexameric subcomplex I from archaeal proteasome consists of coiled-coil segments and OB-fold domains, molecular modeling of 1510-C was performed using hexameric subcomplex I as a template. Although 1510-C is a comparatively small polypeptide consisting of approximately 60 residues, numerous salt bridges and hydrophobic interactions were observed in the predicted hexamer of 1510-C, suggesting the stability of the homo-oligomeric structure. This oligomeric property of STOPP may be favorable for triplicate proteolysis of the trimer of prokaryotic stomatin. PMID:23587725

  7. A systematic study of electron or hole transfer along DNA dimers, trimers and polymers

    CERN Document Server

    Simserides, Constantinos

    2014-01-01

    A systematic study of electron or hole transfer along DNA dimers, trimers and polymers is presented with a tight-binding approach at the base-pair level, using the relevant on-site energies of the base-pairs and the hopping parameters between successive base-pairs. A system of $N$ coupled differential equations is solved numerically with the eigenvalue method, allowing the temporal and spatial evolution of electrons or holes along a $N$ base-pair DNA segment to be determined. Useful physical quantities are defined and calculated including the maximum transfer percentage $p$ and the pure maximum transfer rate $\\frac{p}{T}$ for cases where a period $T$ can be defined, as well as the pure mean carrier transfer rate $k$ and the speed of charge transfer $u=kd$, where $d = N \\times$ 3.4 {\\AA} is the charge transfer distance. The inverse decay length $\\beta$ used for the exponential fit $k = k_0 \\exp(-\\beta d)$ and the exponent $\\eta$ used for the power law fit $k = k_0' N^{-\\eta}$ are computed. The electron and hol...

  8. Excitonic Coupling in Linear and Trefoil Trimer Perylenediimide Molecules Probed by Single-Molecule Spectroscopy

    KAUST Repository

    Yoo, Hyejin

    2012-10-25

    Perylenediimide (PDI) molecules are promising building blocks for photophysical studies of electronic interactions within multichromophore arrays. Such PDI arrays are important materials for fabrication of molecular nanodevices such as organic light-emitting diodes, organic semiconductors, and biosensors because of their high photostability, chemical and physical inertness, electron affinity, and high tinctorial strength over the entire visible spectrum. In this work, PDIs have been organized into linear (L3) and trefoil (T3) trimer molecules and investigated by single-molecule fluorescence microscopy to probe the relationship between molecular structures and interchromophoric electronic interactions. We found a broad distribution of coupling strengths in both L3 and T3 and hence strong/weak coupling between PDI units by monitoring spectral peak shifts in single-molecule fluorescence spectra upon sequential photobleaching of each constituent chromophore. In addition, we used a wide-field defocused imaging technique to resolve heterogeneities in molecular structures of L3 and T3 embedded in a PMMA polymer matrix. A systematic comparison between the two sets of experimental results allowed us to infer the correlation between intermolecular interactions and molecular structures. Our results show control of the PDI intermolecular interactions using suitable multichromophoric structures. © 2012 American Chemical Society.

  9. Synthesis of Cyclododecatriene from 1,3-Butadiene by Trimerization over Amine-Titanium Complex Catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Park, Da Min; Kim, Gye Ryung; Lee, Ju Hyun; Kim, Geon-Joong [Inha University, Incheon (Korea, Republic of); Cho, Deuk Hee [Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of)

    2013-06-15

    The new complex catalysts were synthesized by the reaction of titanium compounds (titanium chloride or titanium butoxide) and diamines in this work, and they showed very high catalytic activities for the cyclododecatriene (CDT) synthesis from 1,3-butadiene through trimerization. CDT synthetic reaction was performed in an autoclave reactor, and the effects of reaction temperature, type of catalyst, catalyst amount added into the system, the mole ratio of Al/Ti and immobilization method were investigated on the yield of product CDT. The titanium complex catalyst combined to diamine with 1:1 ratio showed high selectivity to CDT more than 90%. The ratio of TTT-CDT/TTC-CDT isomers in the product revealed as different values, depending on the type of diamine combined to titanium and Ti/diamine ratios. Those homogeneous complexes could be used as a heterogenized catalyst after anchoring on the supports, and the immobilized titanium catalyst retained the catalytic activities for several times in the recycled reactions without leaching. The carbon support containing titanium has exhibited superior activity to the silica support. Especially, when the titanium complex was anchored on the support which was fabricated by the hydrolysis of tripropylaminosilane itself, the resulting titanium catalyst showed the highest BD conversion and CDT selectivity.

  10. Nature of the extended states in one-dimensional random trimers

    International Nuclear Information System (INIS)

    By using Kronig-Penney model, we examined in this paper the extended states of a non-interacting electron in one-dimensional n-mers randomly placed in a crystal. We found in each band of the energy spectrum n-1 resonances corresponding to extended states of the n-mers. Such resonances become narrower if the crystal support is constituted of potential wells instead of barriers. We studied also the Anderson transition near the two resonances of the random trimer in the first allowed band of the crystal support. We found that this transition is slower at the left side rather than the right side of the first resonance while it behaves similarly for the second one. This is due to the nature of the eigenstates for each resonance. We examined then the wave-functions at these resonances where the first one is not like Bloch-waves but the second one looks like the crystal wave-function with slight distortions. Further discussions are also included. (author). 24 refs, 6 figs

  11. Electrochemical corrosion protection studies of aniline-capped aniline trimer-based electroactive polyurethane coatings

    International Nuclear Information System (INIS)

    In this paper, the successful preparation of electroactive polyurethane (EPU) coatings containing amine-capped aniline trimer (ACAT) is presented for the first time. To accomplish this, ACAT was synthesized by carrying out oxidative coupling reactions between aniline and para-phenylenediamine, after which it was characterized through Fourier-transformation infrared and UV–vis spectroscopy. Subsequently, a polyurethane (PU) prepolymer was prepared by polymerizing diisocyanate of 4,4-methylene-bis(cyclohexylisocyanate), diol of polycaprolactone, and triol of phloroglucinol at 60 °C for 3 h. EPU was then produced by allowing the as-prepared polyurethane prepolymer to react with ACAT under suitable conditions. Non-electroactive polyurethane (NEPU) coating was also prepared for the control experiments. Based on a series of electrochemical corrosion measurements, EPU in the form of a coating was found to possess a clearly enhanced corrosion protection effect when compared to PU. The observed enhancement of the anticorrosion effect of EPU on a metallic substrate when compared to that of NEPU may have been caused by the redox catalytic capability of ACAT present in EPU, inducing the formation of a densely passive metal oxide layer (i.e., Fe2O3 and Fe3O4), as indicated by the results of scanning electron microscopy and electron spectroscopy for chemical analysis. The redox behavior of the EPU coatings was further analyzed and compared to that of the NEPU coating by cyclic voltammetric (CV) studies.

  12. Bacillus cereus Response to a Proanthocyanidin Trimer, a Transcriptional and Functional Analysis.

    Science.gov (United States)

    Tamura, Tomoko; Ozawa, Megumi; Tanaka, Naoto; Arai, Soichi; Mura, Kiyoshi

    2016-07-01

    Proanthocyanidins are abundant in peanut skin, and in this study, the antibacterial effects of a peanut skin extract (PSE) against food-borne bacteria were investigated to find its minimum inhibitory concentration. Food-borne gram-positive bacteria, and in particular Bacillus cereus, was more sensitive to PSE. In particular, the inhibitory activity of epicatechin-(4β → 6)-epicatechin-(2β → O→7, 4β → 8)-catechin (EEC), a proanthocyanidin trimer from peanut skin, against B. cereus was stronger than that of procyanidin A1, a proanthocyanidin dimer. DNA microarray analysis of B. cereus treated with EEC was carried out, with a finding that 597 genes were significantly up-regulated. Analysis of the up-regulated genes suggested that EEC disrupted the normal condition of the cell membrane and wall of B. cereus and alter its usual nutritional metabolism. Moreover, treatment of B. cereus with EEC inhibited glucose uptake, suggesting that EEC affects the cell-surface adsorption. PMID:27061585

  13. A charged residue at the subunit interface of PCNA promotes trimer formation by destabilizing alternate subunit interactions

    International Nuclear Information System (INIS)

    Eukaryotic proliferating cell nuclear antigen (PCNA), an essential accessory factor in DNA replication and repair, is a ring-shaped homotrimer. A novel nontrimeric structure of E113G-mutant PCNA protein is reported, which shows that this protein forms alternate subunit interactions. It is concluded that the charged side chain of Glu113 promotes normal trimer formation by destabilizing these alternate subunit interactions. Eukaryotic proliferating cell nuclear antigen (PCNA) is an essential replication accessory factor that interacts with a variety of proteins involved in DNA replication and repair. Each monomer of PCNA has an N-terminal domain A and a C-terminal domain B. In the structure of the wild-type PCNA protein, domain A of one monomer interacts with domain B of a neighboring monomer to form a ring-shaped trimer. Glu113 is a conserved residue at the subunit interface in domain A. Two distinct X-ray crystal structures have been determined of a mutant form of PCNA with a substitution at this position (E113G) that has previously been studied because of its effect on translesion synthesis. The first structure was the expected ring-shaped trimer. The second structure was an unanticipated nontrimeric form of the protein. In this nontrimeric form, domain A of one PCNA monomer interacts with domain A of a neighboring monomer, while domain B of this monomer interacts with domain B of a different neighboring monomer. The B–B interface is stabilized by an antiparallel β-sheet and appears to be structurally similar to the A–B interface observed in the trimeric form of PCNA. The A–A interface, in contrast, is primarily stabilized by hydrophobic interactions. Because the E113G substitution is located on this hydrophobic surface, the A–A interface should be less favorable in the case of the wild-type protein. This suggests that the side chain of Glu113 promotes trimer formation by destabilizing these possible alternate subunit interactions

  14. Complementation of diverse HIV-1 Env defects through cooperative subunit interactions: a general property of the functional trimer

    Directory of Open Access Journals (Sweden)

    Salzwedel Karl

    2009-08-01

    Full Text Available Abstract Background The HIV-1 Env glycoprotein mediates virus entry by catalyzing direct fusion between the virion membrane and the target cell plasma membrane. Env is composed of two subunits: gp120, which binds to CD4 and the coreceptor, and gp41, which is triggered upon coreceptor binding to promote the membrane fusion reaction. Env on the surface of infected cells is a trimer consisting of three gp120/gp41 homo-dimeric protomers. An emerging question concerns cooperative interactions between the protomers in the trimer, and possible implications for Env function. Results We extended studies on cooperative subunit interactions within the HIV-1 Env trimer, using analysis of functional complementation between coexpressed inactive variants harboring different functional deficiencies. In assays of Env-mediated cell fusion, complementation was observed between variants with a wide range of defects in both the gp120 and gp41 subunits. The former included gp120 subunits mutated in the CD4 binding site or incapable of coreceptor interaction due either to mismatched specificity or V3 loop mutation. Defective gp41 variants included point mutations at different residues within the fusion peptide or heptad repeat regions, as well as constructs with modifications or deletions of the membrane proximal tryptophan-rich region or the transmembrane domain. Complementation required the defective variants to be coexpressed in the same cell. The observed complementation activities were highly dependent on the assay system. The most robust activities were obtained with a vaccinia virus-based expression and reporter gene activation assay for cell fusion. In an alternative system involving Env expression from integrated provirus, complementation was detected in cell fusion assays, but not in virus particle entry assays. Conclusion Our results indicate that Env function does not require every subunit in the trimer to be competent for all essential activities. Through

  15. Evolutionary Conservation of a GPCR-Independent Mechanism of Trimeric G Protein Activation

    Science.gov (United States)

    Coleman, Brantley D.; Marivin, Arthur; Parag-Sharma, Kshitij; DiGiacomo, Vincent; Kim, Seongseop; Pepper, Judy S.; Casler, Jason; Nguyen, Lien T.; Koelle, Michael R.; Garcia-Marcos, Mikel

    2016-01-01

    Trimeric G protein signaling is a fundamental mechanism of cellular communication in eukaryotes. The core of this mechanism consists of activation of G proteins by the guanine-nucleotide exchange factor (GEF) activity of G protein coupled receptors. However, the duration and amplitude of G protein-mediated signaling are controlled by a complex network of accessory proteins that appeared and diversified during evolution. Among them, nonreceptor proteins with GEF activity are the least characterized. We recently found that proteins of the ccdc88 family possess a Gα-binding and activating (GBA) motif that confers GEF activity and regulates mammalian cell behavior. A sequence similarity-based search revealed that ccdc88 genes are highly conserved across metazoa but the GBA motif is absent in most invertebrates. This prompted us to investigate whether the GBA motif is present in other nonreceptor proteins in invertebrates. An unbiased bioinformatics search in Caenorhabditis elegans identified GBAS-1 (GBA and SPK domain containing-1) as a GBA motif-containing protein with homologs only in closely related worm species. We demonstrate that GBAS-1 has GEF activity for the nematode G protein GOA-1 and that the two proteins are coexpressed in many cells of living worms. Furthermore, we show that GBAS-1 can activate mammalian Gα-subunits and provide structural insights into the evolutionarily conserved determinants of the GBA–G protein interface. These results demonstrate that the GBA motif is a functional GEF module conserved among highly divergent proteins across evolution, indicating that the GBA-Gα binding mode is strongly constrained under selective pressure to mediate receptor-independent G protein activation in metazoans. PMID:26659249

  16. Interactions of cationic trimeric, gemini and monomeric surfactants with trianionic curcumin in aqueous solution.

    Science.gov (United States)

    Wang, Meina; Wu, Chunxian; Tang, Yongqiang; Fan, Yaxun; Han, Yuchun; Wang, Yilin

    2014-05-21

    Interactions of trianionic curcumin (Cur(3-)) with a series of cationic surfactants, monomeric surfactant dodecyl trimethylammonium bromide (DTAB), dimeric surfactant hexamethylene-1,6-bis(dodecyldimethylammonium bromide) (12-6-12) and trimeric surfactant tri(dodecyldimethylammonioacetoxy)diethyltriamine trichloride (DTAD), have been investigated in aqueous solution of pH 13.0. Surface tension and spectral measurements indicate that the cationic surfactants display a similar surfactant concentration dependent interaction process with Cur(3-), involving three interaction stages. At first the three cationic surfactants electrostatically bind on Cur(3-) to form the surfactant-Cur(3-) complex. Then the bound and unbound cationic surfactants with Cur(3-) aggregate into surfactant-Cur(3-) mixed micelles through hydrophobic interactions above the critical micelle concentration of the surfactants (CMCC) in the presence of Cur(3-). Finally excess unbound surfactants self-assemble into micelles like those without Cur(3-). For all the three surfactants, the addition of Cur(3-) only decreases the critical micelle concentration of 12-6-12 but does not affect the critical micelle concentration of DTAB and DTAD. As the oligomeric degree of surfactants increases, the intermolecular interaction of the cationic surfactants with Cur(3-) increases and the surfactant amount needed for Cur(3-) encapsulation decreases. Compared with 12-6-12, either the weaker interaction of DTAB with Cur(3-) or stronger interaction of DTAD with Cur(3-) limits the stability or solubility of Cur(3-) in surfactant micelles. Therefore, gemini surfactant 12-6-12 is the best choice to effectively suppress Cur(3-) degradation at very low concentrations. Isothermal titration microcalorimetry, surface tension and (1)H NMR results reveal that 12-6-12 and Cur(3-) form a (12-6-12)2-Cur(3-) complex and start to form micelles at extremely decreased concentrations, where either 12-6-12 or Cur(3-) works as a bridge

  17. Trimeric form of intracellular ATP synthase subunit β of Aggregatibacter actinomycetemcomitans binds human interleukin-1β.

    Directory of Open Access Journals (Sweden)

    Annamari Paino

    Full Text Available Bacterial biofilms resist host defenses and antibiotics partly because of their decreased metabolism. Some bacteria use proinflammatory cytokines, such as interleukin (IL-1β, as cues to promote biofilm formation and to alter virulence. Although one potential bacterial IL-1β receptor has been identified, current knowledge of the bacterial IL-1β sensing mechanism is limited. In chronic biofilm infection, periodontitis, Aggregatibacter actinomycetemcomitans requires tight adherence (tad-locus to form biofilms, and tissue destroying active lesions contain more IL-1β than inactive ones. The effect of IL-1β on the metabolic activity of A. actinomycetemcomitans biofilm was tested using alamarBlue™. The binding of IL-1β to A. actinomycetemcomitans cells was investigated using transmission electron microscopy and flow cytometry. To identify the proteins which interacted with IL-1β, different protein fractions from A. actinomycetemcomitans were run in native-PAGE and blotted using biotinylated IL-1β and avidin-HRP, and identified using mass spectroscopy. We show that although IL-1β slightly increases the biofilm formation of A. actinomycetemcomitans, it reduces the metabolic activity of the biofilm. A similar reduction was observed with all tad-locus mutants except the secretin mutant, although all tested mutant strains as well as wild type strains bound IL-1β. Our results suggest that IL-1β might be transported into the A. actinomycetemcomitans cells, and the trimeric form of intracellular ATP synthase subunit β interacted with IL-1β, possibly explaining the decreased metabolic activity. Because ATP synthase is highly conserved, it might universally enhance biofilm resistance to host defense by binding IL-1β during inflammation.

  18. Novel Anti-Nicotine Vaccine Using a Trimeric Coiled-Coil Hapten Carrier.

    Directory of Open Access Journals (Sweden)

    Keith D Miller

    Full Text Available Tobacco addiction represents one of the largest public health problems in the world and is the leading cause of cancer and heart disease, resulting in millions of deaths a year. Vaccines for smoking cessation have shown considerable promise in preclinical models, although functional antibody responses induced in humans are only modestly effective in preventing nicotine entry into the brain. The challenge in generating serum antibodies with a large nicotine binding capacity is made difficult by the fact that this drug is non-immunogenic and must be conjugated as a hapten to a protein carrier. To circumvent the limitations of traditional carriers like keyhole limpet hemocyanin (KLH, we have synthesized a short trimeric coiled-coil peptide (TCC that creates a series of B and T cell epitopes with uniform stoichiometry and high density. Here we compared the relative activities of a TCC-nic vaccine and two control KLH-nic vaccines using Alum as an adjuvant or GLA-SE, which contains a synthetic TLR4 agonist formulated in a stable oil-in-water emulsion. The results showed that the TCC's high hapten density correlated with a better immune response in mice as measured by anti-nicotine Ab titer, affinity, and specificity, and was responsible for a reduction in anti-carrier immunogenicity. The Ab responses achieved with this synthetic vaccine resulted in a nicotine binding capacity in serum that could prevent >90% of a nicotine dose equivalent to three smoked cigarettes (0.05 mg/kg from reaching the brain.

  19. Evolutionary Conservation of a GPCR-Independent Mechanism of Trimeric G Protein Activation.

    Science.gov (United States)

    Coleman, Brantley D; Marivin, Arthur; Parag-Sharma, Kshitij; DiGiacomo, Vincent; Kim, Seongseop; Pepper, Judy S; Casler, Jason; Nguyen, Lien T; Koelle, Michael R; Garcia-Marcos, Mikel

    2016-03-01

    Trimeric G protein signaling is a fundamental mechanism of cellular communication in eukaryotes. The core of this mechanism consists of activation of G proteins by the guanine-nucleotide exchange factor (GEF) activity of G protein coupled receptors. However, the duration and amplitude of G protein-mediated signaling are controlled by a complex network of accessory proteins that appeared and diversified during evolution. Among them, nonreceptor proteins with GEF activity are the least characterized. We recently found that proteins of the ccdc88 family possess a Gα-binding and activating (GBA) motif that confers GEF activity and regulates mammalian cell behavior. A sequence similarity-based search revealed that ccdc88 genes are highly conserved across metazoa but the GBA motif is absent in most invertebrates. This prompted us to investigate whether the GBA motif is present in other nonreceptor proteins in invertebrates. An unbiased bioinformatics search in Caenorhabditis elegans identified GBAS-1 (GBA and SPK domain containing-1) as a GBA motif-containing protein with homologs only in closely related worm species. We demonstrate that GBAS-1 has GEF activity for the nematode G protein GOA-1 and that the two proteins are coexpressed in many cells of living worms. Furthermore, we show that GBAS-1 can activate mammalian Gα-subunits and provide structural insights into the evolutionarily conserved determinants of the GBA-G protein interface. These results demonstrate that the GBA motif is a functional GEF module conserved among highly divergent proteins across evolution, indicating that the GBA-Gα binding mode is strongly constrained under selective pressure to mediate receptor-independent G protein activation in metazoans. PMID:26659249

  20. Insights on the structure and stability of Licanantase: a trimeric acid-stable coiled-coil lipoprotein from Acidithiobacillus thiooxidans

    Directory of Open Access Journals (Sweden)

    Fernando Abarca

    2014-08-01

    Full Text Available Licanantase (Lic is the major component of the secretome of Acidithiobacillus thiooxidans when grown in elemental sulphur. When used as an additive, Lic improves copper recovery from bioleaching processes. However, this recovery enhancement is not fully understood. In this context, our aim is to predict the 3D structure of Lic, to shed light on its structure-function relationships. Bioinformatics analyses on the amino acid sequence of Lic showed a great similarity with Lpp, an Escherichia coli Lipoprotein that can form stable trimers in solution. Lic and Lpp share the secretion motif, intracellular processing and alpha helix structure, as well as the distribution of hydrophobic residues in heptads forming a hydrophobic core, typical of coiled-coil structures. Cross-linking experiments showed the presence of Lic trimers, supporting our predictions. Taking the in vitro and in silico evidence as a whole, we propose that the most probable structure for Lic is a trimeric coiled-coil. According to this prediction, a suitable model for Lic was produced using the de novo algorithm “Rosetta Fold-and-Dock”. To assess the structural stability of our model, Molecular Dynamics (MD and Replica Exchange MD simulations were performed using the structure of Lpp and a 14-alanine Lpp mutant as controls, at both acidic and neutral pH. Our results suggest that Lic was the most stable structure among the studied proteins in both pH conditions. This increased stability can be explained by a higher number of both intermonomer hydrophobic contacts and hydrogen bonds, key elements for the stability of Lic’s secondary and tertiary structure.

  1. Oligomerization of the SARS-CoV S glycoprotein: dimerization of the N-terminus and trimerization of the ectodomain

    International Nuclear Information System (INIS)

    Viral envelope glycoproteins are oligomeric and the quaternary structure is critical for their membrane fusion activity. Typically the transmembrane glycoproteins of class I fusion proteins contain the oligomerization domains and the surface glycoproteins (SU) are monomeric. However, it has been previously demonstrated [J. Biol. Chem. 277 (2002) 19727] that the SU of a murine hepatitis coronavirus (MHV) forms dimers, the dimerization domain overlaps the receptor-binding domain (RBD) and that this dimeric state is important for binding to receptor molecules that initiates entry into cells. We have previously expressed various soluble fragments of the SARS-CoV SU and identified stably folded fragments (residues 272-537) that contain the RBD [Biochem. Biophys. Res. Commun. 312 (2003) 1159]. Here, we further characterize these and other fragments in an attempt to identify possible dimerization domains and their role for membrane fusion. We demonstrate that the SU and a shorter 260-amino acid N-terminal fragment (residues 17-276), which folds independently, form dimers. In contrast to the previously characterized MHV SU dimerization, this fragment is upstream and distinct from the RBD. Its deletion abolished S-mediated cell membrane fusion but retained the SU-receptor-binding function indicating the possibility for a role in post-receptor binding steps of the virus entry mechanism. Interestingly, the whole soluble S ectodomain (Se) that contains the dimerization domain but not the transmembrane domain and the cytoplasmic tail forms trimers suggesting the existence of a trimerization domain in the TM subunit in its prefusion state that may lead to a conformation unfavorable for formation of higher-order multimeric structures. These results demonstrate the existence of SU dimers and Se trimers, and indicate the possibility for an unknown mechanism of their role in entry. They also further characterize the S-mediated membrane fusion and could be important for understanding

  2. Human surfactant protein A2 gene mutations impair dimmer/trimer assembly leading to deficiency in protein sialylation and secretion.

    Directory of Open Access Journals (Sweden)

    Yi Song

    Full Text Available Surfactant protein A2 (SP-A2 plays an essential role in surfactant metabolism and lung host defense. SP-A2 mutations in the carbohydrate recognition domain have been related to familial pulmonary fibrosis and can lead to a recombinant protein secretion deficiency in vitro. In this study, we explored the molecular mechanism of protein secretion deficiency and the subsequent biological effects in CHO-K1 cells expressing both wild-type and several different mutant forms of SP-A2. We demonstrate that the SP-A2 G231V and F198S mutants impair the formation of dimmer/trimer SP-A2 which contributes to the protein secretion defect. A deficiency in sialylation, but not N-linked glycosylation, is critical to the observed dimmer/trimer impairment-induced secretion defect. Furthermore, both mutant forms accumulate in the ER and form NP-40-insoluble aggregates. In addition, the soluble mutant SP-A2 could be partially degraded through the proteasome pathway but not the lysosome or autophagy pathway. Intriguingly, 4-phenylbutyrate acid (4-PBA, a chemical chaperone, alleviates aggregate formation and partially rescued the protein secretion of SP-A2 mutants. In conclusion, SP-A2 G231V and F198S mutants impair the dimmer/trimer assembly, which contributes to the protein sialylation and secretion deficiency. The intracellular protein mutants could be partially degraded through the proteasome pathway and also formed aggregates. The treatment of the cells with 4-PBA resulted in reduced aggregation and rescued the secretion of mutant SP-A2.

  3. Lateral manipulation of small clusters on the Cu and Ag(1 1 1) surfaces with the single-atom and trimer-apex tips: Reliability study

    International Nuclear Information System (INIS)

    We study the reliability of the lateral manipulation of small Cu clusters (dimer and trimer) on the flat Cu(1 1 1) surface with both the single-atom and trimer-apex tips and that for the Ag/Ag(1 1 1) system, and compare the results between the two systems as well as with the single-atom manipulation on these surfaces. Manipulations are simulated using molecular statics method with semi-empirical potentials. The dependence of the manipulation reliability on the tip height and tip orientation are investigated. Overall, the manipulation reliability increases with decreasing tip height although it depends obviously on the tip orientation. For the Cu/Cu(1 1 1) system, the manipulation of the dimmer and trimer can be successful with both tips. The manipulation reliability can be improved by the trimer-apex tip, and the tip-height range for the successful manipulation is also broader, as compared to the single-atom apex tip. Differently from the single-atom manipulation, the tip orientation has a noticeable influence on the manipulation reliability even for the single-atom tip due to the stronger tip-cluster and surface-adatom interactions in cluster manipulation. For the Ag/Ag(1 1 1) system, successful manipulations only be achieved with the trimer-apex tip, and the manipulation reliability is worse than that of the Cu/Cu(1 1 1) system, indicating the difference in mechanic properties between the two surfaces at the atomic level.

  4. Crystal structure of tetranectin, a trimeric plasminogen-binding protein with an alpha-helical coiled coil

    DEFF Research Database (Denmark)

    Nielsen, B B; Kastrup, J S; Rasmussen, H;

    1997-01-01

    to a long alpha-helix. Tetranectin has been classified in a distinct group of the C-type lectin superfamily but has structural similarity to the proteins in the group of collectins. Tetranectin has three intramolecular disulfide bridges. Two of these are conserved in the C-type lectin superfamily......, whereas the third is present only in long-form CRDs. Tetranectin represents the first structure of a long-form CRD with intact calcium-binding sites. In tetranectin, the third disulfide bridge tethers the CRD to the long helix in the coiled coil. The trimerization of tetranectin as well as the fixation of...

  5. A New Approach to C60-Containing Polyphosphazenes by Polymerization of Phosphonitrile Chloride Trimer in the Presence of C60

    Institute of Scientific and Technical Information of China (English)

    LI Zhen; ZENG Qi; ZHU Zhi-Chao; LI Qian-Qian; LI Zhong-An; QIN Jin-Gui

    2007-01-01

    A novel synthetic strategy was developed to prepare polyphosphazenes containing C60 moieties. Thus, the phosphonitrile chloride trimer underwent thermal ring-opening polymerization (ROP) in the presence of C60 molecules to yield the reactive macromolecular intermediate, C60-containing poly(dichlorophosphazene). And then, the other groups could be linked to the phosphazene backbone by nucleophilic substitution reaction of the chlorine atoms in this intermediate to produce a series of C60-containing polyphosphazene. The polymer exhibits good solubility in common organic solvents and is thermally stable.

  6. Plaquette-triplon analysis of magnetic disorder and order in a trimerized spin-1 kagome Heisenberg antiferromagnet

    Science.gov (United States)

    Ghosh, Pratyay; Verma, Akhilesh Kumar; Kumar, Brijesh

    2016-01-01

    A spin-1 Heisenberg model on trimerized kagome lattice is studied by doing a low-energy bosonic theory in terms of plaquette triplons defined on its triangular unit cells. The model considered has an intratriangle antiferromagnetic exchange interaction J (set to 1) and two intertriangle couplings J'>0 (nearest neighbor) and J″ (next nearest neighbor; of both signs). The triplon analysis performed on this model investigates the stability of the trimerized singlet ground state (which is exact in the absence of intertriangle couplings) in the J'-J″ plane. It gives a quantum phase diagram that has two gapless antiferromagnetically ordered phases separated by the spin-gapped trimerized singlet phase. The trimerized singlet ground state is found to be stable on J″=0 line (the nearest-neighbor case), and on both sides of it for J″≠0 , in an extended region bounded by the critical lines of transition to the gapless antiferromagnetic phases. The gapless phase in the negative J″ region has a coplanar 120∘ antiferromagnetic order with √{3 }×√{3 } structure. In this phase, all the magnetic moments are of equal length, and the angle between any two of them on a triangle is exactly 120∘. The magnetic lattice in this case has a unit cell consisting of three triangles. The other gapless phase, in the positive J″ region, is found to exhibit a different coplanar antiferromagnetic order with ordering wave vector q =(0 ,0 ) . Here, two magnetic moments in a triangle are of the same magnitude, but shorter than the third. While the angle between two short moments is 120∘-2 δ , it is 120∘+δ between a short and the long one. Only when J″=J' , their magnitudes become equal and the relative angles 120∘. The magnetic lattice in this q =(0 ,0 ) phase has the translational symmetry of the kagome lattice with triangular unit cells of reduced (isosceles) symmetry. This reduction in the point-group symmetry is found to show up as a difference in the intensities of

  7. delta-Opioid receptors exhibit high efficiency when activating trimeric G proteins in membrane domains.

    Science.gov (United States)

    Bourova, Lenka; Kostrnova, Alexandra; Hejnova, Lucie; Moravcova, Zuzana; Moon, Hyo-Eun; Novotny, Jiri; Milligan, Graeme; Svoboda, Petr

    2003-04-01

    Low-density membrane fragments (domains) were separated from the bulk of plasma membranes of human embryonic kidney (HEK)293 cells expressing a delta-opioid (DOP) receptor-Gi1alpha fusion protein by drastic homogenization and flotation on equilibrium sucrose density gradients. The functional activity of trimeric G proteins and capacity of the DOP receptor to stimulate both the fusion protein-linked Gi1alpha and endogenous pertussis-toxin sensitive G proteins was measured as d-Ala2, d-Leu5-enkephalin stimulated high-affinity GTPase or guanosine-5'-[gamma-35S]triphosphate ([35S]GTPgammaS) binding. The maximum d-Ala2-d-Leu5 enkephalin (DADLE)-stimulated GTPase was two times higher in low-density membrane fragments than in bulk of plasma membranes; 58 and 27 pmol/mg/min, respectively. The same difference was obtained for [35S]GTPgammaS binding. Contrarily, the low-density domains contained no more than half the DOP receptor binding sites (Bmax = 6.6 pmol/mg versus 13.6 pmol/mg). Thus, when corrected for expression levels of the receptor, low-density domains exhibited four times higher agonist-stimulated GTPase and [35S]GTPgammaS binding than the bulk plasma membranes. The regulator of G protein signaling RGS1, enhanced further the G protein functional activity but did not remove the difference between domain-bound and plasma membrane pools of G protein. The potency of the agonist in functional studies and the affinity of specific [3H]DADLE binding to the receptor were, however, the same in both types of membranes - EC50 = 4.5 +/- 0.1 x 10(-8) and 3.2 +/- 1.4 x 10(-8) m for GTPase; Kd = 1.2 +/- 0.1 and 1.3 +/- 0.1 nm for [3H]DADLE radioligand binding assay. Similar results were obtained when sodium bicarbonate was used for alkaline isolation of membrane domains. By contrast, detergent-insensitive membrane domains isolated following treatment of cells with Triton X100 exhibited no DADLE-stimulated GTPase or GTPgammaS binding. Functional coupling between the DOP receptor

  8. Why do the outer membrane proteins OmpF from E. coli and OprP from P. aeruginosa prefer trimers? Simulation studies.

    Science.gov (United States)

    Niramitranon, Jitti; Sansom, Mark Sp; Pongprayoon, Prapasiri

    2016-04-01

    Porins are water-filled protein channels across the outer membrane of gram-negative bacteria. They facilitate the uptake of nutrients and essential ions. Solutes are filtered by a constriction loop L3 at the mid of a pore. Porins are heat-stable and resistant to toxic agents and detergents. Most porins are trimer, but no clear explanation why trimeric form is preferable. In this work, we thus studied effects of oligomerization on porin structure and function in microscopic detail. A well-studied OmpF (general porin from Escherichia coli) and well-characterised OprP (phosphate-specific pore from Pseudomonas aeruginosa) are used as samples from 2 types of porins found in gram-negative bacteria. MD simulations of trimeric and monomeric pores in pure water and 1M NaCl solution were performed. With a salt solution, the external electric field was applied to mimic a transmembrane potential. Expectedly, OprP is more stable than OmpF. Interestingly, being a monomer turns OmpF into an anion-selective pore. The dislocation of D113's side chain on L3 in OmpF causes the disruption of cation pathway resulting in the reduction of cation influx. In contrast, OprP's structure and function are less dependent on oligomeric states. Both monomeric and trimeric OprP can maintain their anion selectivity. Our findings suggest that trimerization is crucial for both structure and function of general porin OmpF, whereas being trimer in substrate-specific channel OprP supports a pore function. PMID:26895142

  9. Nonperturbative linked-cluster expansions for the trimerized ground state of the spin-one kagome Heisenberg model

    Science.gov (United States)

    Ixert, Dominik; Tischler, Tobias; Schmidt, Kai P.

    2015-11-01

    We use nonperturbative linked-cluster expansions to determine the ground-state energy per site of the spin-one Heisenberg model on the kagome lattice. To this end, a parameter is introduced allowing us to interpolate between a fully trimerized state and the isotropic model. The ground-state energy per site of the full graph decomposition up to graphs of six triangles (18 spins) displays a complex behavior as a function of this parameter close to the isotropic model which we attribute to divergencies of partial series in the graph expansion of quasi-1D unfrustrated chain graphs. More concretely, these divergencies can be traced back to a quantum critical point of the one-dimensional unfrustrated chain of coupled triangles. Interestingly, the reorganization of the nonperturbative linked-cluster expansion in terms of clusters with enhanced symmetry yields a ground-state energy per site of the isotropic two-dimensional model that is in quantitative agreement with other numerical approaches in favor of a spontaneous trimerization of the system. Our findings are of general importance for any nonperturbative linked-cluster expansion on geometrically frustrated systems.

  10. Novel gold nanoparticle trimer reporter probe combined with dry-reagent cotton thread immunoassay device for rapid human ferritin test.

    Science.gov (United States)

    Mao, Xun; Du, Ting-E; Meng, Lili; Song, Tingting

    2015-08-19

    We reported here for the first time on the use of cotton thread combined with novel gold nanoparticle trimer reporter probe for low-cost, sensitive and rapid detection of a lung cancer related biomarker, human ferritin. A model system comprising ferritin as an analyte and a pair of monoclonal antibodies was used to demonstrate the proof-of-concept on the dry-reagent natural cotton thread immunoassay device. Results indicated that the using of novel gold nanoparticle trimer reporter probe greatly improved the sensitivity comparing with traditional gold nanoparticle reporter probe on the cotton thread immunoassay device. The assay avoids multiple incubation and washing steps performed in most conventional protein analyses. Although qualitative tests are realized by observing the color change of the test zone, quantitative data are obtained by recording the optical responses of the test zone with a commercial scanner and corresponding analysis software. Under optimal conditions, the cotton thread immunoassay device was capable of measuring 10 ng/mL human ferritin under room temperature which is sensitive enough for clinical diagnosis. Moreover, the sample solution employed in the assays is just 8 μL, which is much less than traditional lateral flow strip based biosensors. PMID:26343440

  11. Intramolecular trimerization, a novel strategy for making multispecific antibodies with controlled orientation of the antigen binding domains.

    Science.gov (United States)

    Alvarez-Cienfuegos, Ana; Nuñez-Prado, Natalia; Compte, Marta; Cuesta, Angel M; Blanco-Toribio, Ana; Harwood, Seandean Lykke; Villate, Maider; Merino, Nekane; Bonet, Jaume; Navarro, Rocio; Muñoz-Briones, Clara; Sørensen, Karen Marie Juul; Mølgaard, Kasper; Oliva, Baldo; Sanz, Laura; Blanco, Francisco J; Alvarez-Vallina, Luis

    2016-01-01

    Here, we describe a new strategy that allows the rapid and efficient engineering of mono and multispecific trivalent antibodies. By fusing single-domain antibodies from camelid heavy-chain-only immunoglobulins (VHHs) to the N-terminus of a human collagen XVIII trimerization domain (TIE(XVIII)) we produced monospecific trimerbodies that were efficiently secreted as soluble functional proteins by mammalian cells. The purified VHH-TIE(XVIII) trimerbodies were trimeric in solution and exhibited excellent antigen binding capacity. Furthermore, by connecting with two additional glycine-serine-based linkers three VHH-TIE(XVIII) modules on a single polypeptide chain, we present an approach for the rational design of multispecific tandem trimerbodies with defined stoichiometry and controlled orientation. Using this technology we report here the construction and characterization of a tandem VHH-based trimerbody capable of simultaneously binding to three different antigens: carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR) and green fluorescence protein (GFP). Multispecific tandem VHH-based trimerbodies were well expressed in mammalian cells, had good biophysical properties and were capable of simultaneously binding their targeted antigens. Importantly, these antibodies were very effective in inhibiting the proliferation of human epidermoid carcinoma A431 cells. Multispecific VHH-based trimerbodies are therefore ideal candidates for future applications in various therapeutic areas. PMID:27345490

  12. Vibronic spectra predictions for open shell molecules - usefulness and limitations of ab initio calculations, assessed on alkali trimers

    International Nuclear Information System (INIS)

    Full text: The usefulness of standard ab initio techniques, such as coupled-cluster or multi-reference approaches, for the prediction of vibronic spectra is discussed using the example of K3 and Rb3 alkali-metal clusters. These exotic molecules, can be formed in their lowest-energy spin state (the doublet) by standard molecular beam methods; their weakly bound quartet state is easily stabilized on the surface of cold (0.4 K) helium nanodroplets. Both spin multiplicities have been characterized spectroscopically, and are good candidates to assess the quality of ab initio methods for electronic-structure calculations. The following characteristics make alkali trimers interesting in this respect: they are multi-electron systems, of moderate size, and include heavy atoms. Correlation energy and relativistic effects thus play an equally essential role for the molecular binding; at the same time, the system remains tractable by computationally expensive high-level methods. The symmetry properties of alkali trimers, in either spin multiplicity, makes them prime examples for the E.e Jahn-Teller effect, where a doubly-degenerate electronic state interacts with the doubly-degenerate vibrational mode of the system. By least-squares-fits of the ab initio points we extract parameters for the analytical description of the potential energy surfaces of several electronic states. We calculate vibronic spectra where the Jahn-Teller distortion as well as spin-orbit coupling are accounted for, which we compare with the available experimental data. (author)

  13. Thermodynamics of spin- 1/2 antiferromagnet-antiferromagnet-ferromagnet and ferromagnet-ferromagnet-antiferromagnet trimerized quantum Heisenberg chains

    Science.gov (United States)

    Gu, Bo; Su, Gang; Gao, Song

    2006-04-01

    The magnetization process, the susceptibility, and the specific heat of the spin- 1/2 antiferromagnet (AF)-AF-ferromagnet (F) and F-F-AF trimerized quantum Heisenberg chains have been investigated by means of the transfer matrix renormalization group (TMRG) technique as well as the modified spin-wave (MSW) theory. A magnetization plateau at m=1/6 for both trimerized chains is observed at low temperature. The susceptibility and the specific heat show various behaviors for different ferromagnetic and antiferromagnetic interactions and in different magnetic fields. The TMRG results of susceptibility and the specific heat can be nicely fitted by a linear superposition of double two-level systems, where two fitting equations are proposed. Three branch excitations, one gapless excitation and two gapful excitations, for both systems are found within the MSW theory. It is observed that the MSW theory captures the main characteristics of the thermodynamic behaviors at low temperatures. The TMRG results are also compared with the possible experimental data.

  14. GC-MS identification of MIC trimer: a constituent of tank residue in preserved autopsy blood of Bhopal gas victims.

    Science.gov (United States)

    Chandra, H; Rao, G J; Saraf, A K; Sharma, V K; Jadhav, R K; Sriramachari, S

    1991-10-01

    Based on the external and internal findings of Bhopal gas disaster victims, it was apparent that the gases and particulate matter came out as an aerosol. This was possibly the pyrolysed, reformulated, reconjugated suspension of constituents of the tank E-610 of Union Carbide India Limited, Bhopal, while it was claimed to be methyl isocyanate (MIC) only. It was postulated by the manufacturer of MIC, that the material inhaled by the victims of the Bhopal gas disaster does not cross the lung barrier (UCC press conference on 14th December 1984). It was observed that the more the victims ran, the more aerosol they inhaled and the fatalities were observed in such victims. The tissues, which were preserved in the deep freeze, were randomly selected and analysed by GC coupled with MS (ITD) Finnigan MAT, UK. 14 out of 34 autopsy cases showed MIC trimer peak in extracts of blood. This was one of the constituents of the aerosol and was also located in the tank residue, thereby proving that the trimer had passed the lung barrier. PMID:1795611

  15. Circular trimers of gelatinase B/matrix metalloproteinase-9 constitute a distinct population of functional enzyme molecules differentially regulated by tissue inhibitor of metalloproteinases-1

    DEFF Research Database (Denmark)

    Vandooren, Jennifer; Born, Benjamin; Solomonov, Inna;

    2015-01-01

    knowledge about the overall structure of proMMP-9 monomers and multimers is limited. We investigated biochemical, biophysical and functional characteristics of zymogen and activated forms of MMP-9 monomers and multimers. In contrast with a conventional notion of a dimeric nature of MMP-9 homomultimers, we...... in a higher extent of TIMP-1 inhibition of angiogenesis induced by trimers compared with monomers. Our results show that proMMP-9 trimers constitute a novel structural and functional entity that is differentially regulated by TIMP-1....

  16. Thermal instability of the trimeric structure of the N-terminal propeptide of human procollagen type I in relation to assay technology

    DEFF Research Database (Denmark)

    Brandt, J; Krogh, T N; Jensen, Charlotte Harken;

    1999-01-01

    the following conclusions: (a) the trimeric structure of PINP is unstable at 37 degreesC; (b) the two molecular forms represent intact alpha1 chains in trimeric and monomeric forms; (c) thermal transition is an ongoing in vivo process; and (d) this is important in the choice of assay technology. Udgivelsesdato...... to measure the low-molecular weight form. Thermal transition of the high-molecular weight form caused a change in its elution volume but did not change its migration in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Mass spectrometry revealed identical results for both forms. We reached...

  17. Elicitation of neutralizing antibodies directed against CD4-induced epitope(s using a CD4 mimetic cross-linked to a HIV-1 envelope glycoprotein.

    Directory of Open Access Journals (Sweden)

    Antu K Dey

    Full Text Available The identification of HIV-1 envelope glycoprotein (Env structures that can generate broadly neutralizing antibodies (BNAbs is pivotal to the development of a successful vaccine against HIV-1 aimed at eliciting effective humoral immune responses. To that end, the production of novel Env structure(s that might induce BNAbs by presentation of conserved epitopes, which are otherwise occluded, is critical. Here, we focus on a structure that stabilizes Env in a conformation representative of its primary (CD4 receptor-bound state, thereby exposing highly conserved "CD4 induced" (CD4i epitope(s known to be important for co-receptor binding and subsequent virus infection. A CD4-mimetic miniprotein, miniCD4 (M64U1-SH, was produced and covalently complexed to recombinant, trimeric gp140 envelope glycoprotein (gp140 using site-specific disulfide linkages. The resulting gp140-miniCD4 (gp140-S-S-M64U1 complex was recognized by CD4i antibodies and the HIV-1 co-receptor, CCR5. The gp140-miniCD4 complex elicited the highest titers of CD4i binding antibodies as well as enhanced neutralizing antibodies against Tier 1 viruses as compared to gp140 protein alone following immunization of rabbits. Neutralization against HIV-2(7312/V434M and additional serum mapping confirm the specific elicitation of antibodies directed to the CD4i epitope(s. These results demonstrate the utility of structure-based approach in improving immunogenic response against specific region, such as the CD4i epitope(s here, and its potential role in vaccine application.

  18. Crystal structure determinations of macrocyclic ligands, monomeric, trimeric and tetrameric phosphazenes by x-ray diffraction

    International Nuclear Information System (INIS)

    In this study, the crystal structures of the following macrocyciic Schiff base iigandstogether with the monomeric, trimeric and tetrameric phosphazene derivatives are determined by the single crystal X-ray diffraction method. In structure solutions; the intensity data collected on the Enraf-Nonius CAD4 diffractometer for the specified crystals, are processed by MolEN and SHELXS97 and SHELXL97 crystal structure determination and refinement programs incorporated in the WinGX package for the personal computers. The intra-inter molecular interactions are determined by PARST97. The molecular diagrams and figures are drawn by CHEMWIND and ORTEP3 programs. I) (C30H2-8N2O5), 1,5-Di[N-2-oxyphenyl-salicylidene]-3-oxapentane II) (C20H26N202), 2/6-Dioxa-14, 18-diazatricyclo = [18,4,0,0''7'',''1''2]-tetracosa-7,9,11,20,22,24(1 )-hexaene III) (C22H26N2O3), 3,4,6,7,15,16,17,18,19,20,21,27-Dodecahydro-2,5,8-trioxa-16, 20-diazatricyclo (20.4.1''1''6'',''2''00.0''9'',''1''4)heptacosa-9,11,13,22,24,26(1)-hexaene IV) (C21H26N2O3), 3,4,6,7,15,16,17,18,19,20,21-Undecahydro-2,5,6-trioxa-16,20-diaza tricyclo (20.4.0.0''9'',''1''4) hexacosa-9,11,13,22,24,26(1)-hexaene V) (C31H55N2O13P3), 15,21-Bis(diethoxyphosphinoyl)-2,,5,8-trioxa-16,20 diaztri cyclo (20.4.0.0''9'',''1''4) hexacosa-9,11,13,22,24,26(1)-hexaene-Ethylphosphonic Acid-Water (1/1/1) VI) (C23H34N2O9P2.2H2O), 15,21-Bis{2-((hydroxy)(methoxy)phosphoryl))}-2,5,8-trioxa-16, 20-diazatricyclo (20.4.0.0''9'',''1''4) hexacosa-9,11,13,22,24,26(1)-hexaene-Water(1/2) VII) (C13H8Cl4N5O6P3), 2,4-(2,2''2-Methylenebis (4-nitrophenoxy))-2,4,6,6-tetrachlorocyclo-2λ''5, 4λ''5, 6λ''5-triphosphazatriene (ansa) VIII) (C9H11N3OP3Cl5), 2,4,4,6,6-Pentachloro-2-(2,4,6-trimethylphenoxy) cyclo-2λ''5, 4λ''5, 6λ''5 triphosphazatriene IX) (C45H55NO6P2), N-(Bis(2,4,6-trimethylphenoxy) phosphinoyl) -P,P,P-tris(2,4,6-trimethyl-phenoxy) phosphazene X) (C30H76N2P4), trans-2,6-Bis(n-propylamino)-2,4,4,6,8,8-hexa-tert-butylamino cyclo-2λ5, 4λ5, 6λ5,8λ5

  19. Amyloid beta dimers/trimers potently induce cofilin-actin rods that are inhibited by maintaining cofilin-phosphorylation

    Directory of Open Access Journals (Sweden)

    Podlisny Marcia

    2011-01-01

    Full Text Available Abstract Background Previously we reported 1 μM synthetic human amyloid beta1-42 oligomers induced cofilin dephosphorylation (activation and formation of cofilin-actin rods within rat hippocampal neurons primarily localized to the dentate gyrus. Results Here we demonstrate that a gel filtration fraction of 7PA2 cell-secreted SDS-stable human Aβ dimers and trimers (Aβd/t induces maximal neuronal rod response at ~250 pM. This is 4,000-fold more active than traditionally prepared human Aβ oligomers, which contain SDS-stable trimers and tetramers, but are devoid of dimers. When incubated under tyrosine oxidizing conditions, synthetic human but not rodent Aβ1-42, the latter lacking tyrosine, acquires a marked increase (620 fold for EC50 in rod-inducing activity. Gel filtration of this preparation yielded two fractions containing SDS-stable dimers, trimers and tetramers. One, eluting at a similar volume to 7PA2 Aβd/t, had maximum activity at ~5 nM, whereas the other, eluting at the void volume (high-n state, lacked rod inducing activity at the same concentration. Fractions from 7PA2 medium containing Aβ monomers are not active, suggesting oxidized SDS-stable Aβ1-42 dimers in a low-n state are the most active rod-inducing species. Aβd/t-induced rods are predominantly localized to the dentate gyrus and mossy fiber tract, reach significance over controls within 2 h of treatment, and are reversible, disappearing by 24 h after Aβd/t washout. Overexpression of cofilin phosphatases increase rod formation when expressed alone and exacerbate rod formation when coupled with Aβd/t, whereas overexpression of a cofilin kinase inhibits Aβd/t-induced rod formation. Conclusions Together these data support a mechanism by which Aβd/t alters the actin cytoskeleton via effects on cofilin in neurons critical to learning and memory.

  20. A computational study of dimers and trimers of nitrosyl hydride: Blue shift of NH bonds that are involved in H-bond and orthogonal interactions

    Energy Technology Data Exchange (ETDEWEB)

    Solimannejad, Mohammad, E-mail: m-solimannejad@araku.ac.ir [Quantum Chemistry Group, Department of Chemistry, Arak University, 38156-879 Arak (Iran, Islamic Republic of); Massahi, Shokofeh [Quantum Chemistry Group, Department of Chemistry, Arak University, 38156-879 Arak (Iran, Islamic Republic of); Alkorta, Ibon, E-mail: ibon@iqm.csic.es [Instituto de Quimica Medica (CSIC), Juan de la Cierva, 3, 28006 Madrid (Spain)

    2009-07-30

    Ab initio calculations at MP2/aug-cc-pVTZ level were used to analyze the interactions between nitrosyl hydride (HNO) dimers and trimers. The structures obtained have been analyzed with the Atoms in Molecules (AIMs) and Natural Bond Orbital (NBO) methodologies. Four minima were located on the potential energy surface of the dimers. Nine different structures have been obtained for the trimers. Three types of interactions are observed, NH{center_dot}{center_dot}{center_dot}N and NH{center_dot}{center_dot}{center_dot}O hydrogen bonds and orthogonal interaction between the lone pair of the oxygen with the electron-deficient region of the nitrogen atom. Stabilization energies of dimers and trimers including BSSE and ZPE are in the range 4-8 kJ mol{sup -1} and 12-19 kJ mol{sup -1}, respectively. Blue shift of NH bond upon complex formation in the ranges between 30-80 and 14,114 cm{sup -1} is predicted for dimers and trimers, respectively.

  1. Organolithium compounds catalyzed trimerization of nitriles and study on the catalystic charateristics%有机锂化合物催化合成均三嗪

    Institute of Scientific and Technical Information of China (English)

    李敏; 黄淑萍; 刘滇生; 李思殿

    2003-01-01

    The imine salt was formed initially by the addition of an organolithium compound to the aromatic nitricle. This type of reaction usually leads to cyclic products, such as triazines. We discussed the mechanism of organolithium compounds catalyzed trimerization of nitriles and study the catalystic charateristics. Using this new method, the yield of triazines was improved.

  2. A method of test for residual isophorone diisocyanate trimer in new polyester-polyurethane coatings on light metal packaging using liquid chromatography with tandem mass spectrometric detection.

    Science.gov (United States)

    Driffield, Malcolm; Bradley, Emma L; Castle, Laurence

    2007-02-01

    A method of test for residual isophorone diisocyanate (IPDI) trimer in experimental formulation polyester-polyurethane (PEPU) thermoset coatings on metal food packaging is described. The method involves extraction of coated panels using acetonitrile containing dibutylamine for concurrent derivatisation, and then high performance liquid chromatography with electrospray ionisation tandem mass spectrometric detection (LC-MS/MS). Single laboratory validation was carried out using three different experimental PEPU-based coatings. The calibrations were linear, the analytical recovery was good, no interferences were seen, and substance identification criteria were met. The detection limit of the method is around 0.02 micro g/100 cm(2) of coating, which for a typical sized can and assuming complete migration of any residual IPDI trimer, corresponds to about 0.2 micro g/kg food or beverage. Separate studies indicated that, even if migration occurred at such low levels, the IPDI trimer would not be expected to persist in canned aqueous or fatty foodstuffs as it would hydrolyse to the corresponding aliphatic amine or react with food components to destroy the isocyanate moiety. The method of test developed here for residual IPDI trimer in thermoset polyester-polyurethane coatings should prove to be a valuable tool for investigating the cure kinetics of these novel coatings and help to guide the development of enhanced formulations. PMID:17178416

  3. Modeling of the N-terminal Section and the Lumenal Loop of Trimeric Light Harvesting Complex II (LHCII) by Using EPR.

    Science.gov (United States)

    Fehr, Niklas; Dietz, Carsten; Polyhach, Yevhen; von Hagens, Tona; Jeschke, Gunnar; Paulsen, Harald

    2015-10-23

    The major light harvesting complex II (LHCII) of green plants plays a key role in the absorption of sunlight, the regulation of photosynthesis, and in preventing photodamage by excess light. The latter two functions are thought to involve the lumenal loop and the N-terminal domain. Their structure and mobility in an aqueous environment are only partially known. Electron paramagnetic resonance (EPR) has been used to measure the structure of these hydrophilic protein domains in detergent-solubilized LHCII. A new technique is introduced to prepare LHCII trimers in which only one monomer is spin-labeled. These heterogeneous trimers allow to measure intra-molecular distances within one LHCII monomer in the context of a trimer by using double electron-electron resonance (DEER). These data together with data from electron spin echo envelope modulation (ESEEM) allowed to model the N-terminal protein section, which has not been resolved in current crystal structures, and the lumenal loop domain. The N-terminal domain covers only a restricted area above the superhelix in LHCII, which is consistent with the "Velcro" hypothesis to explain thylakoid grana stacking (Standfuss, J., van Terwisscha Scheltinga, A. C., Lamborghini, M., and Kühlbrandt, W. (2005) EMBO J. 24, 919-928). The conformation of the lumenal loop domain is surprisingly different between LHCII monomers and trimers but not between complexes with and without neoxanthin bound. PMID:26316535

  4. Recombinant trimeric HA protein immunogenicity of H5N1 avian influenza viruses and their combined use with inactivated or adenovirus vaccines.

    Directory of Open Access Journals (Sweden)

    Shih-Chang Lin

    Full Text Available BACKGROUND: The highly pathogenic avian influenza (HPAI H5N1 virus continues to cause disease in poultry and humans. The hemagglutinin (HA envelope protein is the primary target for subunit vaccine development. METHODOLOGY/PRINCIPAL FINDINGS: We used baculovirus-insect cell expression to obtain trimeric recombinant HA (rHA proteins from two HPAI H5N1 viruses. We investigated trimeric rHA protein immunogenicity in mice via immunizations, and found that the highest levels of neutralizing antibodies resulted from coupling with a PELC/CpG adjuvant. We also found that the combined use of trimeric rHA proteins with (a an inactivated H5N1 vaccine virus, or (b a recombinant adenovirus encoding full-length HA sequences for prime-boost immunization, further improved antibody responses against homologous and heterologous H5N1 virus strains. Data from cross-clade prime-boost immunization regimens indicate that sequential immunization with different clade HA antigens increased antibody responses in terms of total IgG level and neutralizing antibody titers. CONCLUSION/SIGNIFICANCE: Our findings suggest that the use of trimeric rHA in prime-boost vaccine regimens represents an alternative strategy for recombinant H5N1 vaccine development.

  5. Functionalization of nanoparticle titanium dioxide with different bifunctional organic molecules and trimers of transition compounds for obtaining new materials

    International Nuclear Information System (INIS)

    Functionalization of titanium dioxide in nanoporous anatase phase is investigated for obtaining new nanomaterials. Functionalizations were performed using two heating methods: the conventional of refluxing heating method and microwave irradiation with bifunctional organic molecules is used to study how to anchor molecules and the change in the wettability of the material. Besides, reactions with organic molecules were performed as the derived from nanoproxene. The growth layer by layer is performed using the bifunctional molecules previous for the immobilization of cobalt trimers. Functionalized molecules were characterized by infrared spectroscopy, X-ray diffraction, contact angle, scanning electron microscopy, x-ray elemental analysis, plasma atomic emission spectroscopy coupled inductively, x-ray photoelectron spectroscopy and thermogravimetric analysis. This type of functionalizations on nanoporous titanium dioxide could potentially improve optical sensitivity and activity of this nanomaterial in the visible region. (author)

  6. Intramolecular trimerization, a novel strategy for making multispecific antibodies with controlled orientation of the antigen binding domains

    DEFF Research Database (Denmark)

    Álvarez-Cienfuegos, Ana; Alanes, Natalia Nuñez del Prado; Compte, Marta;

    2016-01-01

    Here, we describe a new strategy that allows the rapid and efficient engineering of mono and multispecific trivalent antibodies. By fusing single-domain antibodies from camelid heavy-chain-only immunoglobulins (VHHs) to the N-terminus of a human collagen XVIII trimerization domain (TIEXVIII) we...... three VHH-TIEXVIII modules on a single polypeptide chain, we present an approach for the rational design of multispecific tandem trimerbodies with defined stoichiometry and controlled orientation. Using this technology we report here the construction and characterization of a tandem VHH-based trimerbody...... of simultaneously binding their targeted antigens. Importantly, these antibodies were very effective in inhibiting the proliferation of human epidermoid carcinoma A431 cells. Multispecific VHH-based trimerbodies are therefore ideal candidates for future applications in various therapeutic areas....

  7. The Arabidopsis Cellulose Synthase Complex: A Proposed Hexamer of CESA Trimers in an Equimolar Stoichiometry

    Energy Technology Data Exchange (ETDEWEB)

    Hill, Joseph L. [Pennsylvania State Univ., University Park, PA (United States); Hammudi, Mustafa B. [Pennsylvania State Univ., University Park, PA (United States); Tien, Ming [Pennsylvania State Univ., University Park, PA (United States)

    2014-12-01

    In this study, we show a 1:1:1 stoichiometry between the three Arabidopsis thaliana secondary cell wall isozymes: CESA4, CESA7, and CESA8. This ratio was determined utilizing a simple but elegant method of quantitative immunoblotting using isoform-specific antibodies and 35S-labeled protein standards for each CESA. Additionally, the observed equimolar stoichiometry was found to be fixed along the axis of the stem, which represents a developmental gradient. Our results complement recent spectroscopic analyses pointing toward an 18-chain cellulose microfibril. Taken together, we propose that the CSC is composed of a hexamer of catalytically active CESA trimers, with each CESA in equimolar amounts. This finding is a crucial advance in understanding how CESAs integrate to form higher order complexes, which is a key determinate of cellulose microfibril and cell wall properties.

  8. Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies

    Directory of Open Access Journals (Sweden)

    Laura E. McCoy

    2016-08-01

    Full Text Available A major advance in the search for an HIV vaccine has been the development of a near-native Envelope trimer (BG505 SOSIP.664 that can induce robust autologous Tier 2 neutralization. Here, potently neutralizing monoclonal antibodies (nAbs from rabbits immunized with BG505 SOSIP.664 are shown to recognize an immunodominant region of gp120 centered on residue 241. Residue 241 occupies a hole in the glycan defenses of the BG505 isolate, with fewer than 3% of global isolates lacking a glycan site at this position. However, at least one conserved glycan site is missing in 89% of viruses, suggesting the presence of glycan holes in most HIV isolates. Serum evidence is consistent with targeting of holes in natural infection. The immunogenic nature of breaches in the glycan shield has been under-appreciated in previous attempts to understand autologous neutralizing antibody responses and has important potential consequences for HIV vaccine design.

  9. Recombinant Soluble Respiratory Syncytial Virus F Protein That Lacks Heptad Repeat B, Contains a GCN4 Trimerization Motif and Is Not Cleaved Displays Prefusion-Like Characteristics.

    Directory of Open Access Journals (Sweden)

    Ivy Widjaja

    Full Text Available The respiratory syncytial virus (RSV fusion protein F is considered an attractive vaccine candidate especially in its prefusion conformation. We studied whether recombinant soluble RSV F proteins could be stabilized in a prefusion-like conformation by mutation of heptad repeat B (HRB. The results show that soluble, trimeric, non-cleaved RSV F protein, produced by expression of the furin cleavage site-mutated F ectodomain extended with a GCN4 trimerization sequence, is efficiently recognized by pre- as well as postfusion-specific antibodies. In contrast, a similar F protein completely lacking HRB displayed high reactivity with prefusion-specific antibodies recognizing antigenic site Ø, but did not expose postfusion-specific antigenic site I, in agreement with this protein maintaining a prefusion-like conformation. These features were dependent on the presence of the GCN4 trimerization domain. Absence of cleavage also contributed to binding of prefusion-specific antibodies. Similar antibody reactivity profiles were observed when the prefusion form of F was stabilized by the introduction of cysteine pairs in HRB. To study whether the inability to form the 6HB was responsible for the prefusion-like antibody reactivity profile, alanine mutations were introduced in HRB. Although introduction of alanine residues in HRB inhibited the formation of the 6HB, the exposure of postfusion-specific antigenic site I was not prevented. In conclusion, proteins that are not able to form the 6HB, due to mutation of HRB, may still display postfusion-specific antigenic site I. Replacement of HRB by the GCN4 trimerization domain in a non-cleaved soluble F protein resulted, however, in a protein with prefusion-like characteristics, suggesting that this HRB-lacking protein may represent a potential prefusion F protein subunit vaccine candidate.

  10. Disulfide-dependent self-assembly of adiponectin octadecamers from trimers and presence of stable octadecameric adiponectin lacking disulfide bonds in vitro.

    Science.gov (United States)

    Briggs, David B; Jones, Christopher M; Mashalidis, Ellene H; Nuñez, Martha; Hausrath, Andrew C; Wysocki, Vicki H; Tsao, Tsu-Shuen

    2009-12-29

    Adiponectin is a circulating insulin-sensitizing hormone that homooligomerizes into trimers, hexamers, and higher molecular weight (HMW) species. Low levels of circulating HMW adiponectin appear to increase the risk for insulin resistance. Currently, assembly of adiponectin oligomers and, consequently, mechanisms responsible for decreased HMW adiponectin in insulin resistance are not well understood. In the work reported here, we analyzed the reassembly of the most abundant HMW adiponectin species, the octadecamer, following its collapse to smaller oligomers in vitro. Purified bovine serum adiponectin octadecamer was treated with reducing agents at pH 5 to obtain trimers. These reduced trimers partially and spontaneously reassembled into octadecamers upon oxidative formation of disulfide bonds. Disulfide bonds appear to occupy a greater role in the process of oligomerization than in the structural stabilization of mature octadecamer. Stable octadecamers lacking virtually all disulfide bonds could be observed in abundance using native gel electrophoresis, dynamic light scattering, and collision-induced dissociation nanoelectrospray ionization mass spectrometry. These findings indicate that while disulfide bonds help to maintain the mature octadecameric adiponectin structure, their more important function is to stabilize intermediates during the assembly of octadecamer. Adiponectin oligomerization must proceed through intermediates that are at least partially reduced. Accordingly, fully oxidized adiponectin hexamers failed to reassemble into octadecamers at a rate comparable to that of reduced trimers. As the findings from the present study are based on in vitro experiments, their in vivo relevance remains unclear. Nevertheless, they describe a redox environment-dependent model of adiponectin oligomerization that can be tested using cell-based approaches. PMID:19943704

  11. Trimeric autotransporter adhesins in members of the Burkholderia cepacia complex: a multifunctional family of proteins implicated in virulence

    Directory of Open Access Journals (Sweden)

    Arsénio Mendes Fialho

    2011-12-01

    Full Text Available Trimeric autotransporter adhesins (TAAs are multimeric surface proteins, involved in various biological traits of pathogenic Gram-negative bacteria including adherence, biofilm formation, invasion, survival within eukaryotic cells, serum resistance and cytotoxicity. TAAs have a modular architecture composed by a conserved membrane-anchored C-terminal domain and a variable number of stalk and head domains. In this study, a bioinformatic approach has been used to analyze the distribution and architecture of TAAs among Burkholderia cepacia complex (Bcc genomes. Fifteen genomes were probed revealing a total of 74 encoding sequences. Compared with other bacterial species, the Bcc genomes contain a disproportionately large number of TAAs (two genes to up to 8 genes, such as in B.cenocepacia. Phylogenetic analysis showed that the TAAs grouped into at least eight distinct clusters. TAAs with serine-rich repeats are clearly well separated from others, thereby representing a different evolutionary lineage. Comparative gene mapping across Bcc genomes reveals that TAA genes are inserted within conserved synteny blocks. We further focused our analysis on the epidemic strain B. cenocepacia J2315 in which 7 TAAs were annotated. Among these, 3 TAA-encoding genes (BCAM019, BCAM0223 and BCAM0224 are organized into a cluster and are candidates for multifunctional virulence factors. Here we review the current insights into the functional role of BCAM0224 as a model locus.

  12. Structural Diversity in the Complexes of Trimeric Perfluoro- o -phenylene Mercury with Tetrathia- and Tetramethyltetraselenafulvalene

    Energy Technology Data Exchange (ETDEWEB)

    Castañeda, Raúl [New Mexico Highlands Univ., Las Vegas, NV (United States); Yakovenko, Andrey A. [Argonne National Lab. (ANL), Argonne, IL (United States); Draguta, Sergiu [New Mexico Highlands Univ., Las Vegas, NV (United States); Fonari, Marina S. [New Mexico Highlands Univ., Las Vegas, NV (United States); Academy of Sciences of Moldova, Chisinau (Moldova); Antipin, Mikhail Yu. [New Mexico Highlands Univ., Las Vegas, NV (United States); Russian Academy of Sciences (RAS), Moscow (Russian Federation); Timofeeva, Tatiana V. [New Mexico Highlands Univ., Las Vegas, NV (United States); ITMO Univ., St. Petersburg (Russia)

    2015-03-04

    Five potential charge transfer complexes of trimeric perfluoro-o-phenylene mercury (I) with tetrathiafulvalene (TTF) and tetramethyltetraselenefulvalene (TMTSF) were grown from different solvent mixtures. The adducts (I)2·TTF (1) and I·TTF (2) were grown by slow evaporation from the 1:1 mixture of dichloromethane (CH2Cl2, DCM) and carbon disulfide (CS2). Use of the different 1:1 solvent mixtures of dichloromethane (CH2Cl2, DCM) and dichloroethane (C2H4Cl2, DCE) has led to the crystalline adducts I·TTF (3) and I·TTF·DCE (4). Adduct I.TMTSF (5) was grown by the interface crystallization on the border of two immiscible layers, ethyl acetate, and carbon disulfide. The cocrystals differ by the donor–acceptor ratio, molecular packing, and the solvent inclusion. The components in 1–5 form mixed donor–acceptor stacks. The stacks are stabilized by Hg···S and Hg···C short contacts, while the lateral interactions between stacks include F···F, CH···F, and S/Se···F short contacts.

  13. Immunogenic properties of a trimeric gp41-based immunogen containing an exposed membrane-proximal external region.

    Science.gov (United States)

    Habte, Habtom H; Banerjee, Saikat; Shi, Heliang; Qin, Yali; Cho, Michael W

    2015-12-01

    The membrane-proximal external region (MPER) of HIV-1 gp41 is an attractive target for vaccine development. Thus, better understanding of its immunogenic properties in various structural contexts is important. We previously described the crystal structure of a trimeric protein complex named gp41-HR1-54Q, which consists of the heptad repeat regions 1 and 2 and the MPER. The protein was efficiently recognized by broadly neutralizing antibodies. Here, we describe its immunogenic properties in rabbits. The protein was highly immunogenic, especially the C-terminal end of the MPER containing 4E10 and 10E8 epitopes ((671)NWFDITNWLWYIK(683)). Although antibodies exhibited strong competition activity against 4E10 and 10E8, neutralizing activity was not detected. Detailed mapping analyses indicated that amino acid residues critical for recognition resided on faces of the alpha helix that are either opposite of or perpendicular to the epitopes recognized by 4E10 and 10E8. These results provide critical information for designing the next generation of MPER-based immunogens. PMID:26454663

  14. Charge-ordering transition in iron oxide Fe4O5 involving competing dimer and trimer formation

    Science.gov (United States)

    Ovsyannikov, Sergey V.; Bykov, Maxim; Bykova, Elena; Kozlenko, Denis P.; Tsirlin, Alexander A.; Karkin, Alexander E.; Shchennikov, Vladimir V.; Kichanov, Sergey E.; Gou, Huiyang; Abakumov, Artem M.; Egoavil, Ricardo; Verbeeck, Johan; McCammon, Catherine; Dyadkin, Vadim; Chernyshov, Dmitry; van Smaalen, Sander; Dubrovinsky, Leonid S.

    2016-05-01

    Phase transitions that occur in materials, driven, for instance, by changes in temperature or pressure, can dramatically change the materials’ properties. Discovering new types of transitions and understanding their mechanisms is important not only from a fundamental perspective, but also for practical applications. Here we investigate a recently discovered Fe4O5 that adopts an orthorhombic CaFe3O5-type crystal structure that features linear chains of Fe ions. On cooling below ∼150 K, Fe4O5 undergoes an unusual charge-ordering transition that involves competing dimeric and trimeric ordering within the chains of Fe ions. This transition is concurrent with a significant increase in electrical resistivity. Magnetic-susceptibility measurements and neutron diffraction establish the formation of a collinear antiferromagnetic order above room temperature and a spin canting at 85 K that gives rise to spontaneous magnetization. We discuss possible mechanisms of this transition and compare it with the trimeronic charge ordering observed in magnetite below the Verwey transition temperature.

  15. An Acinetobacter trimeric autotransporter adhesin reaped from cells exhibits its nonspecific stickiness via a highly stable 3D structure.

    Science.gov (United States)

    Yoshimoto, Shogo; Nakatani, Hajime; Iwasaki, Keita; Hori, Katsutoshi

    2016-01-01

    Trimeric autotransporter adhesins (TAAs), cell surface proteins of Gram-negative bacteria, mediate bacterial adhesion to host cells and extracellular matrix proteins. However, AtaA, a TAA in the nonpathogenic Acinetobacter sp. strain Tol 5, shows nonspecific, high adhesiveness to abiotic material surfaces as well as to biotic surfaces. AtaA is a homotrimer of polypeptides comprising 3,630 amino acids and forms long nanofibers; therefore, it is too large and structurally complex to be produced as a recombinant protein. In this study, we isolated AtaA's passenger domain (AtaA PSD), which is translocated to the cell surface through the C-terminal transmembrane domain and exhibits biological functions, using a new method. We introduced a protease recognition site and reaped AtaA nanofibers 225 nm in length from the cell surface through proteolytic cleavage with a specific protease. Biochemical and biophysical analyses of the purified native AtaA PSD revealed that it has a stable structure under alkaline and acidic conditions. Temperatures above 80 °C, which disrupted AtaA's higher-order structure but maintained the full-length AtaA polypeptide, inactivated AtaA's nonspecific adhesiveness, suggesting that the stickiness of AtaA requires its 3D structure. This finding refutes the widespread but vague speculation that large unfolded polypeptides readily stick to various surfaces. PMID:27305955

  16. Cryo-reconstructions of P22 polyheads suggest that phage assembly is nucleated by trimeric interactions among coat proteins

    International Nuclear Information System (INIS)

    Bacteriophage P22 forms an isometric capsid during normal assembly, yet when the coat protein (CP) is altered at a single site, helical structures (polyheads) also form. The structures of three distinct polyheads obtained from F170L and F170A variants were determined by cryo-reconstruction methods. An understanding of the structures of aberrant assemblies such as polyheads helps to explain how amino acid substitutions affect the CP, and these results can now be put into the context of CP pseudo-atomic models. F170L CP forms two types of polyhead and each has the CP organized as hexons (oligomers of six CPs). These hexons have a skewed structure similar to that in procapsids (precursor capsids formed prior to dsDNA packaging), yet their organization differs completely in polyheads and procapsids. F170A CP forms only one type of polyhead, and though this has hexons organized similarly to hexons in F170L polyheads, the hexons are isometric structures like those found in mature virions. The hexon organization in all three polyheads suggests that nucleation of procapsid assembly occurs via a trimer of CP monomers, and this drives formation of a T = 7, isometric particle. These variants also form procapsids, but they mature quite differently: F170A expands spontaneously at room temperature, whereas F170L requires more energy. The P22 CP structure along with scaffolding protein interactions appear to dictate curvature and geometry in assembled structures and residue 170 significantly influences both assembly and maturation

  17. Structural basis for activation of trimeric Gi proteins by multiple growth factor receptors via GIV/Girdin

    Science.gov (United States)

    Lin, Changsheng; Ear, Jason; Midde, Krishna; Lopez-Sanchez, Inmaculada; Aznar, Nicolas; Garcia-Marcos, Mikel; Kufareva, Irina; Abagyan, Ruben; Ghosh, Pradipta

    2014-01-01

    A long-standing issue in the field of signal transduction is to understand the cross-talk between receptor tyrosine kinases (RTKs) and heterotrimeric G proteins, two major and distinct signaling hubs that control eukaryotic cell behavior. Although stimulation of many RTKs leads to activation of trimeric G proteins, the molecular mechanisms behind this phenomenon remain elusive. We discovered a unifying mechanism that allows GIV/Girdin, a bona fide metastasis-related protein and a guanine-nucleotide exchange factor (GEF) for Gαi, to serve as a direct platform for multiple RTKs to activate Gαi proteins. Using a combination of homology modeling, protein–protein interaction, and kinase assays, we demonstrate that a stretch of ∼110 amino acids within GIV C-terminus displays structural plasticity that allows folding into a SH2-like domain in the presence of phosphotyrosine ligands. Using protein–protein interaction assays, we demonstrated that both SH2 and GEF domains of GIV are required for the formation of a ligand-activated ternary complex between GIV, Gαi, and growth factor receptors and for activation of Gαi after growth factor stimulation. Expression of a SH2-deficient GIV mutant (Arg 1745→Leu) that cannot bind RTKs impaired all previously demonstrated functions of GIV—Akt enhancement, actin remodeling, and cell migration. The mechanistic and structural insights gained here shed light on the long-standing questions surrounding RTK/G protein cross-talk, set a novel paradigm, and characterize a unique pharmacological target for uncoupling GIV-dependent signaling downstream of multiple oncogenic RTKs. PMID:25187647

  18. Construction and expression of a humanized M2 autoantigen trimer and its application in the diagnosis of primary biliary cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hua Jiang; Ren-Qian Zhong; Sheng-Qian Yu; Yin Hu; Weng-Weng Li; Xian-Tao Kong

    2003-01-01

    AIM: To construct and express a humanized M2 autoantigen trimer designated as BPO and to apply it in the diagnosis of primary biliary cirrhosis (PBC). METHODS: cDNA fragments encoding M2-reactive epitopes of pyruvate dehydrogenase complex Ez (PDCE2), branched chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) and 2-oxo-glutarate dehydrogenase complex E2 (OGDC-E2) were amplified with PCR using total RNA extracted from human peripheral mononuclear blood cells. The fragments were cloned into the plasmid vector pQE-30 and then transferred into E. coliM15 (pREP4) for expression, which was induced by isopropylthio-β-Dgalactoside. The expressed recombinant BPO protein was demonstrated by SDS-PAGE, Western-blotting and Immunoabsorption test, its antigenic reactivity and specificity were identified with seven M2-positive sera confirmed at Euroimmun Research Center (Germany).Using the purified BPO, M2 antibodies in sera from patients with PBC and other liver related diseases were detected with ELISA. RESULTS: The expressed BPO was observed with both antigenic reactivity and specificity of M2 autoantigens. The determination of M2 antibodies by BPO with ELISA was more sensitive than using the Euroimmun's kit with the coefficients of variation less than 10 % in both interassay and intraassay.With the newly established method, M2 antibodies were found in 100 % (20/20) of patients with PBC. Six cases of liver disease with unknown etiology and 1 patient with drug induced liver injury had detectable levels of serum M2antibodies. There were also 2 patients with autoimmune cholangitis and 1 with autoimmune hepatitis showing M2-antibody positive. CONCLUSION: Compared with the routine immunofluorescenoe assay and commercially available assay kit using porcine heart mitochondrial protein as the antigen, the detection system established in the present study shows higher sensitivity and specificity and may be used as a powerful tool for the diagnosis of PBC.

  19. The trimeric serine protease HtrA1 forms a cage-like inhibition complex with an anti-HtrA1 antibody.

    Science.gov (United States)

    Ciferri, Claudio; Lipari, Michael T; Liang, Wei-Ching; Estevez, Alberto; Hang, Julie; Stawicki, Scott; Wu, Yan; Moran, Paul; Elliott, Mike; Eigenbrot, Charles; Katschke, Kenneth J; van Lookeren Campagne, Menno; Kirchhofer, Daniel

    2015-12-01

    High temperature requirement A1 (HtrA1) is a trypsin-fold serine protease implicated in the progression of age-related macular degeneration (AMD). Our interest in an antibody therapy to neutralize HtrA1 faces the complication that the target adopts a trimeric arrangement, with three active sites in close proximity. In the present study, we describe antibody 94, obtained from a human antibody phage display library, which forms a distinct macromolecular complex with HtrA1 and inhibits the enzymatic activity of recombinant and native HtrA1 forms. Using biochemical methods and negative-staining EM we were able to elucidate the molecular composition of the IgG94 and Fab94 complexes and the associated inhibition mechanism. The 246-kDa complex between the HtrA1 catalytic domain trimer (HtrA1_Cat) and Fab94 had a propeller-like organization with one Fab bound peripherally to each protomer. Low-resolution EM structures and epitope mapping indicated that the antibody binds to the surface-exposed loops B and C of the catalytic domain, suggesting an allosteric inhibition mechanism. The HtrA1_Cat-IgG94 complex (636 kDa) is a cage-like structure with three centrally located IgG94 molecules co-ordinating two HtrA1_Cat trimers and the six active sites pointing into the cavity of the cage. In both complexes, all antigen-recognition regions (paratopes) are found to bind one HtrA1 protomer and all protomers are bound by a paratope, consistent with the complete inhibition of enzyme activity. Therefore, in addition to its potential therapeutic usefulness, antibody 94 establishes a new paradigm of multimeric serine protease inhibition. PMID:26385991

  20. β-Arrestin interacts with the beta/gamma subunits of trimeric G-proteins and dishevelled in the Wnt/Ca(2+ pathway in xenopus gastrulation.

    Directory of Open Access Journals (Sweden)

    Katharina Seitz

    Full Text Available β-Catenin independent, non-canonical Wnt signaling pathways play a major role in the regulation of morphogenetic movements in vertebrates. The term non-canonical Wnt signaling comprises multiple, intracellularly divergent, Wnt-activated and β-Catenin independent signaling cascades including the Wnt/Planar Cell Polarity and the Wnt/Ca(2+ cascades. Wnt/Planar Cell Polarity and Wnt/Ca(2+ pathways share common effector proteins, including the Wnt ligand, Frizzled receptors and Dishevelled, with each other and with additional branches of Wnt signaling. Along with the aforementioned proteins, β-Arrestin has been identified as an essential effector protein in the Wnt/β-Catenin and the Wnt/Planar Cell Polarity pathway. Our results demonstrate that β-Arrestin is required in the Wnt/Ca(2+ signaling cascade upstream of Protein Kinase C (PKC and Ca(2+/Calmodulin-dependent Protein Kinase II (CamKII. We have further characterized the role of β-Arrestin in this branch of non-canonical Wnt signaling by knock-down and rescue experiments in Xenopus embryo explants and analyzed protein-protein interactions in 293T cells. Functional interaction of β-Arrestin, the β subunit of trimeric G-proteins and Dishevelled is required to induce PKC activation and membrane translocation. In Xenopus gastrulation, β-Arrestin function in Wnt/Ca(2+ signaling is essential for convergent extension movements. We further show that β-Arrestin physically interacts with the β subunit of trimeric G-proteins and Dishevelled, and that the interaction between β-Arrestin and Dishevelled is promoted by the beta/gamma subunits of trimeric G-proteins, indicating the formation of a multiprotein signaling complex.

  1. Exploring the conformational and binding properties of unphosphorylated/phosphorylated monomeric and trimeric Bcl-2 through docking and molecular dynamics simulations.

    Science.gov (United States)

    Zacarías-Lara, Oscar J; Correa-Basurto, José; Bello, Martiniano

    2016-07-01

    B-cell lymphoma (Bcl-2) is commonly associated with the progression and preservation of cancer and certain lymphomas; therefore, it is considered as a biological target against cancer. Nevertheless, evidence of all its structural binding sites has been hidden because of the lack of a complete Bcl-2 model, given the presence of a flexible loop domain (FLD), which is responsible for its complex behavior. FLD region has been implicated in phosphorylation, homotrimerization, and heterodimerization associated with Bcl-2 antiapoptotic function. In this contribution, homology modeling, molecular dynamics (MD) simulations in the microsecond (µs) time-scale and docking calculations were combined to explore the conformational complexity of unphosphorylated/phosphorylated monomeric and trimeric Bcl-2 systems. Conformational ensembles generated through MD simulations allowed for identifying the most populated unphosphorylated/phosphorylated monomeric conformations, which were used as starting models to obtain trimeric complexes through protein-protein docking calculations, also submitted to µs MD simulations. Principal component analysis showed that FLD represents the main contributor to total Bcl-2 mobility, and is affected by phosphorylation and oligomerization. Subsequently, based on the most representative unphosphorylated/phosphorylated monomeric and trimeric Bcl-2 conformations, docking studies were initiated to identify the ligand binding site of several known Bcl-2 inhibitors to explain their influence in homo-complex formation and phosphorylation. Docking studies showed that the different conformational states experienced by FLD, such as phosphorylation and oligomerization, play an essential role in the ability to make homo and hetero-complexes. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 393-413, 2016. PMID:27016043

  2. Bipartite Topology of Treponema pallidum Repeat Proteins C/D and I: OUTER MEMBRANE INSERTION, TRIMERIZATION, AND PORIN FUNCTION REQUIRE A C-TERMINAL β-BARREL DOMAIN.

    Science.gov (United States)

    Anand, Arvind; LeDoyt, Morgan; Karanian, Carson; Luthra, Amit; Koszelak-Rosenblum, Mary; Malkowski, Michael G; Puthenveetil, Robbins; Vinogradova, Olga; Radolf, Justin D

    2015-05-01

    We previously identified Treponema pallidum repeat proteins TprC/D, TprF, and TprI as candidate outer membrane proteins (OMPs) and subsequently demonstrated that TprC is not only a rare OMP but also forms trimers and has porin activity. We also reported that TprC contains N- and C-terminal domains (TprC(N) and TprC(C)) orthologous to regions in the major outer sheath protein (MOSP(N) and MOSP(C)) of Treponema denticola and that TprC(C) is solely responsible for β-barrel formation, trimerization, and porin function by the full-length protein. Herein, we show that TprI also possesses bipartite architecture, trimeric structure, and porin function and that the MOSP(C)-like domains of native TprC and TprI are surface-exposed in T. pallidum, whereas their MOSP(N)-like domains are tethered within the periplasm. TprF, which does not contain a MOSP(C)-like domain, lacks amphiphilicity and porin activity, adopts an extended inflexible structure, and, in T. pallidum, is tightly bound to the protoplasmic cylinder. By thermal denaturation, the MOSP(N) and MOSP(C)-like domains of TprC and TprI are highly thermostable, endowing the full-length proteins with impressive conformational stability. When expressed in Escherichia coli with PelB signal sequences, TprC and TprI localize to the outer membrane, adopting bipartite topologies, whereas TprF is periplasmic. We propose that the MOSP(N)-like domains enhance the structural integrity of the cell envelope by anchoring the β-barrels within the periplasm. In addition to being bona fide T. pallidum rare outer membrane proteins, TprC/D and TprI represent a new class of dual function, bipartite bacterial OMP. PMID:25805501

  3. Maturation of dendritic cells by recombinant human CD40L-trimer leads to a homogeneous cell population with enhanced surface marker expression and increased cytokine production

    DEFF Research Database (Denmark)

    Würtzen, P A; Nissen, Mogens Holst; Claesson, M H

    2001-01-01

    -cell activating capacity of the DC. We studied DC phenotype and cytokine production as well as the T-cell proliferation and cytotoxic T lympocyte (CTL) activation induced by DC generated in vitro. In addition, the effect of exposure to recombinant human CD40L-trimer (huCD40LT) on these parameters was investigated....... Effective differentiation of monocytes derived from freshly isolated peripheral blood mononuclear cells (PBMC) was obtained with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4. The DC expression of human leucocyte antigen (HLA) molecules, CD80, CD83, and CD86 was markedly...

  4. Reliable lateral manipulation of a single Ag adatom on a Ag(1 1 1) surface with a trimer-apex tip

    International Nuclear Information System (INIS)

    We study the reliability of the lateral manipulation of a single Ag adatom on a Ag(1 1 1) surface with the single-atom and trimer-apex tips based on molecular statics simulations using surface embedded-atom-method potential. The dependence of the manipulation reliability on tip height and orientation is investigated. For the single-atom tip the manipulation reliability increases monotonically with decreasing tip height, which is owing to the strengthened lateral tip-adatom interaction as the tip height lowers. For the trimer-apex tip, the manipulation reliability is sensitive to the tip orientation in the lower tip-height range, while in the higher tip-height range the manipulation reliability is independent of the tip orientation and moreover can be greatly improved due to the strong vertical attraction of the tip on the adatom as compared to the single-atom tip. We also compare these results to those for manipulating single Cu adatoms on the Cu(1 1 1) surface, reveal the underlying physics, and propose the method to improve the manipulation reliability for different systems.

  5. Femtosecond X-ray solution scattering reveals that bond formation mechanism of a gold trimer complex is independent of excitation wavelength.

    Science.gov (United States)

    Kim, Kyung Hwan; Kim, Jong Goo; Oang, Key Young; Kim, Tae Wu; Ki, Hosung; Jo, Junbeom; Kim, Jeongho; Sato, Tokushi; Nozawa, Shunsuke; Adachi, Shin-Ichi; Ihee, Hyotcherl

    2016-07-01

    The [Au(CN)2 (-)]3 trimer in water experiences a strong van der Waals interaction between the d(10) gold atoms due to large relativistic effect and can serve as an excellent model system to study the bond formation process in real time. The trimer in the ground state (S0) exists as a bent structure without the covalent bond between the gold atoms, and upon the laser excitation, one electron in the antibonding orbital goes to the bonding orbital, thereby inducing the formation of a covalent bond between gold atoms. This process has been studied by various time-resolved techniques, and most of the interpretation on the structure and dynamics converge except that the structure of the first intermediate (S1) has been debated due to different interpretations between femtosecond optical spectroscopy and femtosecond X-ray solution scattering. Recently, the excitation wavelength of 267 nm employed in our previous scattering experiment was suggested as the culprit for misinterpretation. Here, we revisited this issue by performing femtosecond X-ray solution scattering with 310 nm excitation and compared the results with our previous study employing 267 nm excitation. The data show that a linear S1 structure is formed within 500 fs regardless of excitation wavelength and the structural dynamics observed at both excitation wavelengths are identical to each other within experimental errors. PMID:27191012

  6. Membrane-bound SIV envelope trimers are immunogenic in ferrets after intranasal vaccination with a replication-competent canine distemper virus vector.

    Science.gov (United States)

    Zhang, Xinsheng; Wallace, Olivia; Wright, Kevin J; Backer, Martin; Coleman, John W; Koehnke, Rebecca; Frenk, Esther; Domi, Arban; Chiuchiolo, Maria J; DeStefano, Joanne; Narpala, Sandeep; Powell, Rebecca; Morrow, Gavin; Boggiano, Cesar; Zamb, Timothy J; Richter King, C; Parks, Christopher L

    2013-11-01

    We are investigating canine distemper virus (CDV) as a vaccine vector for the delivery of HIV envelope (Env) that closely resembles the native trimeric spike. We selected CDV because it will promote vaccine delivery to lymphoid tissues, and because human exposure is infrequent, reducing potential effects of pre-existing immunity. Using SIV Env as a model, we tested a number of vector and gene insert designs. Vectors containing a gene inserted between the CDV H and L genes, which encoded Env lacking most of its cytoplasmic tail, propagated efficiently in Vero cells, expressed the immunogen on the cell surface, and incorporated the SIV glycoprotein into progeny virus particles. When ferrets were vaccinated intranasally, there were no signs of distress, vector replication was observed in the gut-associated lymphoid tissues, and the animals produced anti-SIV Env antibodies. These data show that live CDV-SIV Env vectors can safely induce anti-Env immune responses following intranasal vaccination. PMID:24074564

  7. Enantioselective Syntheses of Lignin Models: An Efficient Synthesis of β-O-4 Dimers and Trimers by Using the Evans Chiral Auxiliary.

    Science.gov (United States)

    Njiojob, Costyl N; Bozell, Joseph J; Long, Brian K; Elder, Thomas; Key, Rebecca E; Hartwig, William T

    2016-08-22

    We describe an efficient five-step, enantioselective synthesis of (R,R)- and (S,S)-lignin dimer models possessing a β-O-4 linkage, by using the Evans chiral aldol reaction as a key step. Mitsunobu inversion of the (R,R)- or (S,S)-isomers generates the corresponding (R,S)- and (S,R)-diastereomers. We further extend this approach to the enantioselective synthesis of a lignin trimer model. These lignin models are synthesized with excellent ee (>99 %) and high overall yields. The lignin dimer models can be scaled up to provide multigram quantities that are not attainable by using previous methodologies. These lignin models will be useful in degradation studies probing the selectivity of enzymatic, microbial, and chemical processes that deconstruct lignin. PMID:27459234

  8. Mixed-Stack Architecture and Solvatomorphism of Trimeric Perfluoro-ortho-Phenylene Mercury complexes with Dithieno[3,2-b:2',3'-d]thiophene

    KAUST Repository

    Castañeda, Raúl

    2015-08-01

    The formation of the mixed-stack donor-acceptor complex of dithieno[3,2-b:2\\',3\\'-d]thiophene (1) and trimeric perfluoro-ortho-phenylene mercury (I) has been investigated under different conditions. Two solvatomorphs – mixed-stack complexes with a 1:1 donor-acceptor ratio and different solvent molecules in the solid state (dichloromethane (2) and dichloroethane (3)) have been obtained and characterized by experimental methods (FT-IR spectroscopy, differential thermogravimetric analysis, and X-ray crystallography) and quantum-chemical calculations at the density functional theory level. The differences in the solid state packing, thermal stability and potential charge-transfer properties of 2 and 3 are discussed.

  9. Unusual bonding modes of perfluorobenzene in its polymeric (dimeric, trimeric and tetrameric) forms: entirely negative fluorine interacting cooperatively with entirely negative fluorine.

    Science.gov (United States)

    Varadwaj, Pradeep R; Varadwaj, Arpita; Jin, Bih-Yaw

    2015-12-21

    The F(δ-)···F(δ-) intermolecular synthon was recently observed to be useful for generating a two-dimensional layered supramolecular architecture on the Ag(111) surface (Kawai, et al., ACS Nano, 2015). This was formed when the entirely negative covalently bonded fluorine atoms in phenyleneethynylene(bis(2,3,5,6-tetrafluoro-4-(2,3,4,5,6-pentafluorophenylethynyl)phenyl)-ethyne (BPEPE-F18)) were in close proximity to the same atoms in another BPEPE-F18 molecule. With a view to provide rigorous insights into the physical chemistry of such an intermolecular synthon, we have selected perfluorobenzene (C6F6) as a model compound, and have performed extensive DFT-M06-2X/6-311++G(d,p) investigations on a number of its homomolecular dimers, trimers, and tetramers. Of the twelve (C6F6)2 dimers investigated, a displaced-parallel arrangement with an uncorrected binding energy (ΔE) of -7.4 kcal mol(-1) was found to be the most stable, and an incorporation of the basis set superposition error (BSSE) has significantly reduced its ΔE to -4.7 kcal mol(-1). Besides, the ΔE for a minimum-energy least stable conformation of the same dimer, which involves a single σhole(-)···σhole(-) type F(δ-)···F(δ-) intermolecular bonding interaction, amounts to -0.62 and -0.24 kcal mol(-1) without and with BSSE, respectively. The geometry of another conformation of the dimer, which accompanies a set of three F(δ-)···F(δ-) intermolecular interactions somehow similarly to those observed in the layered supramolecular structure formed by the BPEPE-F18 molecules, lies at a relative energy of 6.5 kcal mol(-1) above the most stable conformation. Passing from the latter dimer to an analogous (C6F6)3 trimer, as well as from the trimer to an analogous (C6F6)4 tetramer, the latter two clusters comprising windmill-type F(δ-)···F(δ-) intermolecular topologies, we have marked a preferential increase in the value of ΔE from -0.94 (dimer) to -2.76 (trimer) to -4.49 kcal mol(-1) (tetramer

  10. The true nature of the Di-iron(III) gamma-Keggin structure in water: catalytic aerobic oxidation and chemistry of an unsymmetrical trimer.

    Science.gov (United States)

    Botar, Bogdan; Geletii, Yurii V; Kögerler, Paul; Musaev, Djamaladdin G; Morokuma, Keiji; Weinstock, Ira A; Hill, Craig L

    2006-08-30

    The complex [gamma(1,2)-SiW(10){Fe(OH(2))}(2)O(38)](6)(-) (1) has been reported to catalyze the much sought reductant-free selective O(2)-based epoxidation of alkenes (Nishiyama, Y.; Nakagawa, Y.; Mizuno, N. Angew. Chem. Int. Ed. 2001, 40, 3639-3641) in chlorocarbon-acetonitrile solution. The challenge of reproducing catalysis by 1 led us to examine this chemistry in detail. In H(2)O, a desirable solvent for catalysis, 1, does not exist in the proposed organic-medium form in which the two iron atoms are in the binding pocket defined by the equatorial oxygens and, importantly, by two oxygens bound to the central Si heteroatom. Instead, 1 in H(2)O initially forms an unusual trimer [{Fe(2)(OH)(3)(H(2)O)(2)}(3)(gamma-SiW(10)O(36))(3)](15)(-) (2). The X-ray structure of 2 shows that the Fe-O(Si) bonds are cleaved and new bonds (mu-hydroxo bridges) form between these Fe centers and those of the neighboring [gamma(1,2)-SiW(10)Fe(2)] units. Structural, physical, and computational evidence indicate that if the bonds between the d-electron center, M (Fe in the case of 1 and 2), and the terminal ligands on M are stronger than the M-O(x)() bonds, then the out-of-pocket form is more stable and is the one observed. Significantly, 2 in H(2)O forms an intermediate that catalyzes the effective aerobic oxidation of sulfur compounds (mercaptoethanol is oxidized to the corresponding disulfide by O(2) at ambient pressure and temperature). All experimental findings are consistent with dissociation of a gamma-SiW(10) Keggin unit from the trimer, 2, to form the catalytically active species. PMID:16925446

  11. TprC/D (Tp0117/131), a Trimeric, Pore-Forming Rare Outer Membrane Protein of Treponema pallidum, Has a Bipartite Domain Structure

    Science.gov (United States)

    Anand, Arvind; Luthra, Amit; Dunham-Ems, Star; Caimano, Melissa J.; Karanian, Carson; LeDoyt, Morgan; Cruz, Adriana R.; Salazar, Juan C.

    2012-01-01

    Identification of Treponema pallidum rare outer membrane proteins (OMPs) has been a longstanding objective of syphilis researchers. We recently developed a consensus computational framework that employs a battery of cellular localization and topological prediction tools to generate ranked clusters of candidate rare OMPs (D. L. Cox et al., Infect. Immun. 78:5178–5194, 2010). TP0117/TP0131 (TprC/D), a member of the T. pallidum repeat (Tpr) family, was a highly ranked candidate. Circular dichroism, heat modifiability by SDS-PAGE, Triton X-114 phase partitioning, and liposome incorporation confirmed that full-length, recombinant TprC (TprCFl) forms a β-barrel capable of integrating into lipid bilayers. Moreover, TprCFl increased efflux of terbium-dipicolinic acid complex from large unilamellar vesicles and migrated as a trimer by blue-native PAGE. We found that in T. pallidum, TprC is heat modifiable, trimeric, expressed in low abundance, and, based on proteinase K accessibility and opsonophagocytosis assays, surface exposed. From these collective data, we conclude that TprC is a bona fide rare OMP as well as a functional ortholog of Escherichia coli OmpF. We also discovered that TprC has a bipartite architecture consisting of a soluble N-terminal portion (TprCN), presumably periplasmic and bound directly or indirectly to peptidoglycan, and a C-terminal β-barrel (TprCC). Syphilitic rabbits generate antibodies exclusively against TprCC, while secondary syphilis patients fail to mount a detectable antibody response against either domain. The syphilis spirochete appears to have resolved a fundamental dilemma arising from its extracellular lifestyle, namely, how to enhance OM permeability without increasing its vulnerability to the antibody-mediated defenses of its natural human host. PMID:22389487

  12. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques

    Directory of Open Access Journals (Sweden)

    Roger Le Grand

    2013-07-01

    Full Text Available HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb. We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

  13. SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env cause AIDS in rhesus monkeys

    OpenAIRE

    Siddappa Nagadenahalli B; Kramer Victor G; Chenine Agnès L; Sharma Prachi; Ong Helena; Song Ruijiang; Rasmussen Robert A; Humbert Michael; Xu Weidong; Else James G; Novembre Francis J; Strobert Elizabeth; O'Neil Shawn P; Ruprecht Ruth M

    2008-01-01

    Abstract Background Infection of nonhuman primates with simian immunodeficiency virus (SIV) or chimeric simian-human immunodeficiency virus (SHIV) strains is widely used to study lentiviral pathogenesis, antiviral immunity and the efficacy of AIDS vaccine candidates. SHIV challenges allow assessment of anti-HIV-1 envelope responses in primates. As such, SHIVs should mimic natural HIV-1 infection in humans and, to address the pandemic, encode HIV-1 Env components representing major viral subty...

  14. Preparation of Methylated Products of A-type Procyanidin Trimers in Cinnamon Bark and Their Protective Effects on Pancreatic β-Cell.

    Science.gov (United States)

    Chen, Lu; Chen, Liang; Wang, Ting; Yuan, Pulong; Chen, Kaixian; Jia, Qi; Wang, Heyao; Li, Yiming

    2016-05-01

    Polyphenols are partial metabolized to methylated conjugations in vivo, and then could modify bioavailability and bioactivity related to the uptake of parent compounds. Our previous studies have found that the antidiabetic effects of cinnamon barks are mainly related to polyphenol components, particularly A-type procyanidin trimer cinnamtannin-1 (CT1). It is necessary to understand the antidiabetic activity of methylations of CT1, nevertheless, sufficient amounts of methylated CT1 are difficult to obtain from metabolites in vivo. In this study, O-methyl derivatives of CT1 were prepared through one-pot methyl iodide reaction and isolation via column chromatography and RP-HPLC semipreparation. The structures of O-methyl substituents were determined through NMR (Nuclear Magnetic Resonance) and HPLC-ESI-MS (High-performance liquid chromatography-electrospray ionization-mass spectrometry). Five purified O-methyl substituents and 2 isomers of CT1 were obtained. Their protective effects on a palmitic acid-induced pancreatic β-cell apoptosis model were then evaluated. Results showed that the protective effects on pancreatic β-cell of O-methyl substituents were weaker than those of CT1. The results suggested that the methylation of catechol groups could be a relevant factor contributing to the decline of protective effects on pancreatic β-cell of CT1 via obstructing quinone intermediate formation and affecting antioxidant abilities. The antidiabetic effects of O-methyl derivatives of CT1 should be further determined by other antidiabetic models. PMID:27074527

  15. AtaA, a new member of the trimeric autotransporter adhesins from Acinetobacter sp. Tol 5 mediating high adhesiveness to various abiotic surfaces.

    Directory of Open Access Journals (Sweden)

    Masahito Ishikawa

    Full Text Available Acinetobacter sp. Tol 5 exhibits an autoagglutinating nature and noteworthy adhesiveness to various abiotic surfaces from hydrophobic plastics to hydrophilic glass and stainless steel. Although previous studies have suggested that bacterionanofibers on Tol 5 cells are involved in the adhesive phenotype of Tol 5, the fiber that directly mediates Tol 5 adhesion has remained unknown. Here, we present a new member of trimeric autotransporter adhesins designated AtaA, which we discovered by analyzing a less adhesive mutant of Tol 5, T1, obtained by transposon mutagenesis. AtaA forms thinner and shorter nanofibers than fimbriae on Tol 5 cells. We performed target disruption of ataA by allelic marker exchange, and the resulting ΔataA strain was complemented with ataA on the Escherichia coli-Acinetobacter shuttle vector, which was newly constructed. These results proved that AtaA is essential for Tol 5's autoagglutinating nature and high adhesiveness to surfaces of various materials. In addition, the adhesiveness to solid surfaces mediated by AtaA is notably higher than that mediated by YadA of Yersinia enterocolitica WA-314. Moreover, and importantly, these characteristics can be conferred to the non-adhesive, non-agglutinating bacterium Acinetobacter sp. ADP1 in trans by transformation with ataA, with expected applications to microbial immobilization.

  16. Tetrairon and hexairon hydroxo/acetato clusters stabilized by multiple polyoxometalate scaffolds. Structures, magnetic properties, and chemistry of a dimer and a trimer.

    Science.gov (United States)

    Botar, Bogdan; Kögerler, Paul; Hill, Craig L

    2007-06-25

    Investigation of the catalytically relevant gamma-diiron(III) Keggin complexes in aqueous acetate buffer leads to a dimeric C(2v)-symmetric polyanion, [{Fe(OH)(OAc)}(4)(gamma-SiW(10)O(36))(2)](12-) (3) and a trimeric C(2)-symmetric polyanion, [{Fe(6)(OH)(9)(H(2)O)(2)(OAc)(2)}(gamma-SiW(10)O(36))(3)](17-) (4). Polyanion 3 incorporates a hydroxo/acetato-bridged tetrairon(III) core, while 4 incorporates a trigonal prismatic hydroxo/acetato-bridged hexairon(III) core. The monomeric building unit of 3 and 4, {gamma-SiW(10)Fe(2)}, adopts the "out-of-pocket" structural motif (with two corner-sharing FeO(6) coordination polyhedra no longer connected to the internal SiO(4) tetrahedron of the Keggin unit) also observed in the {gamma-SiW(10)Fe(2)}(-)type structures isolated from nonbuffered aqueous solutions. Following hydrolysis, 3 is converted to 4 as confirmed by (29)Si NMR. Magnetic measurements establish that in both 3 and 4 all exchange interactions are antiferromagnetic. PMID:17518464

  17. Defect induced intermittency in the transit time dynamics generates 1/f noise in a trimer described by the discrete nonlinear Schroedinger equation

    International Nuclear Information System (INIS)

    We investigate the nonlinear dynamics in a trimer, described by the one-dimensional discrete nonlinear Schrodinger equation (DNLSE), with periodic boundary conditions in the presence of a single on-site defect. We make use of numerical continuation to study different families of stationary and periodic solutions, which allows us to consider suitable perturbations. Taking into account a Poincare section, we are able to study the dynamics in both a thin stochastic layer solution and a global stochasticity solution. We find that the time series of the transit times, the time intervals to traverse some suitable sets in phase space, generate 1/f noise for both stochastic solutions. In the case of the thin stochastic layer solution, we find that transport between two almost invariant sets along with intermittency in small and large time scales are relevant features of the dynamics. These results are reflected in the behaviour of the standard map with suitable parameters. In both chaotic solutions, the distribution of transit times has a maximum and a tail with exponential decay in spite of the presence of long-range correlations in the time series. We motivate our study by considering a ring of weakly-coupled Bose-Einstein condensates (BEC) with attractive interactions, where inversion of populations between two spatially symmetric sites and phase locking take place in both chaotic solutions. (author)

  18. Bulge-out structures in the single-stranded trimer AUA and in the duplex (CUGGUGCGG).(CCGCCCAG). A model-building and NMR study.

    Science.gov (United States)

    van den Hoogen, Y T; van Beuzekom, A A; de Vroom, E; van der Marel, G A; van Boom, J H; Altona, C

    1988-01-01

    Model-building studies were carried out on the trimer AUA. Bulge-out structures which allow incorporation into a continuous RNA helix were generated and energy-minimized. All geometrical features obtained by previous NMR studies on purine-pyrimidine-purine sequences are accounted for in these models. One of the models was used to fit into a double helical fragment. Only minor changes were necessary to construct a central bulge-out in an otherwise intact duplex. NMR and model-building studies were performed on the duplex (CUGGUGCGG).(CCGCCCAG) which contains an unpaired uridine residue. NOE data, chemical-shift profiles and imino-proton resonances provided evidence that the extra U is bulged out of the duplex. The relatively small dispersion in 31P chemical shifts (approximately equal to 0.7 ppm) indicate the absence of t/g or g/t combinations for the phosphodiester angles zeta/alpha. An energy-minimized model of the duplex, which fits the present collection of data, is presented. PMID:3387215

  19. A novel trimeric Zn (II) complex based on 8-hydroxyquinoline with trifluoromethylbenzene group: Synthesis, crystal structure, photophysical properties and DNA binding

    Science.gov (United States)

    Huo, Yanping; Wang, Chunquan; Lu, Jiguo; Hu, Sheng; Li, Xiaoyang; Zhang, Li

    2015-10-01

    A novel 2-substituted-8-hydroxyquinoline ligand (E)-2-[2-(4-trifluoromethylphenyl)ethenyl]-8-hydroxyquinoline (3, HL) was synthesized and characterized by ESI-MS, NMR spectroscopy and elemental analysis. Using solvothermal method, a trimeric complex [Zn3L6] (4) was fabricated by self-assembly of Zn(II) ions with 3. X-ray structural analysis shows that 4 exhibits a trinuclear core, which was bridged and encapsulated by six 8-hydroxyquinolinate-based ligands. The supramolecular structure of 4 features a lamellar solid constructed by aromatic stacking interactions and nonclassical C-H···F hydrogen bonds derived from 4-trifluoromethylphenyl group of the 3. The coordination behavior of zinc salt and 3 in solution was performed by 1H NMR, UV-vis and Photoluminescence (PL). The experimental results show that the complex 4 emits yellow luminescence in the solid state. To investigate its properties further, we also studied the thermal stability, photophysical properties (fluorescent emission, lifetime) of complex 4, and the interactions between 4 and C60 or EtBr-DNA system.

  20. Photoionization of cold gas phase coronene and its clusters: Autoionization resonances in monomer, dimer, and trimer and electronic structure of monomer cation

    International Nuclear Information System (INIS)

    Polycyclic aromatic hydrocarbons (PAHs) are key species encountered in a large variety of environments such as the Interstellar Medium (ISM) and in combustion media. Their UV spectroscopy and photodynamics in neutral and cationic forms are important to investigate in order to learn about their structure, formation mechanisms, and reactivity. Here, we report an experimental photoelectron-photoion coincidence study of a prototypical PAH molecule, coronene, and its small clusters, in a molecular beam using the vacuum ultraviolet (VUV) photons provided by the SOLEIL synchrotron facility. Mass-selected high resolution threshold photoelectron (TPES) and total ion yield spectra were obtained and analyzed in detail. Intense series of autoionizing resonances have been characterized as originating from the monomer, dimer, and trimer neutral species, which may be used as spectral fingerprints for their detection in the ISM by VUV absorption spectroscopy. Finally, a full description of the electronic structure of the monomer cation was made and discussed in detail in relation to previous spectroscopic optical absorption data. Tentative vibrational assignments in the near-threshold TPES spectrum of the monomer have been made with the support of a theoretical approach based on density functional theory

  1. Photoionization of cold gas phase coronene and its clusters: Autoionization resonances in monomer, dimer, and trimer and electronic structure of monomer cation

    Energy Technology Data Exchange (ETDEWEB)

    Bréchignac, Philippe, E-mail: philippe.brechignac@u-psud.fr; Falvo, Cyril; Parneix, Pascal; Pino, Thomas; Pirali, Olivier [Institut des Sciences Moléculaires d’Orsay, CNRS UMR8214, Univ Paris-Sud, F-91405 Orsay (France); Garcia, Gustavo A.; Nahon, Laurent [Synchrotron SOLEIL, L’Orme des Merisiers, Saint-Aubin, B.P. 48, F-91192 Gif-sur-Yvette (France); Joblin, Christine; Kokkin, Damian; Bonnamy, Anthony [IRAP, Université de Toulouse 3 - CNRS, 9 Av. Colonel Roche, B.P. 44346, F-31028 Toulouse Cedex 4 (France); Mulas, Giacomo [INAF - Osservatorio Astronomico di Cagliari, via della scienza 5, I-09047 Selargius (Italy)

    2014-10-28

    Polycyclic aromatic hydrocarbons (PAHs) are key species encountered in a large variety of environments such as the Interstellar Medium (ISM) and in combustion media. Their UV spectroscopy and photodynamics in neutral and cationic forms are important to investigate in order to learn about their structure, formation mechanisms, and reactivity. Here, we report an experimental photoelectron-photoion coincidence study of a prototypical PAH molecule, coronene, and its small clusters, in a molecular beam using the vacuum ultraviolet (VUV) photons provided by the SOLEIL synchrotron facility. Mass-selected high resolution threshold photoelectron (TPES) and total ion yield spectra were obtained and analyzed in detail. Intense series of autoionizing resonances have been characterized as originating from the monomer, dimer, and trimer neutral species, which may be used as spectral fingerprints for their detection in the ISM by VUV absorption spectroscopy. Finally, a full description of the electronic structure of the monomer cation was made and discussed in detail in relation to previous spectroscopic optical absorption data. Tentative vibrational assignments in the near-threshold TPES spectrum of the monomer have been made with the support of a theoretical approach based on density functional theory.

  2. Photoionization of cold gas phase coronene and its clusters: autoionization resonances in monomer, dimer, and trimer and electronic structure of monomer cation.

    Science.gov (United States)

    Bréchignac, Philippe; Garcia, Gustavo A; Falvo, Cyril; Joblin, Christine; Kokkin, Damian; Bonnamy, Anthony; Parneix, Pascal; Pino, Thomas; Pirali, Olivier; Mulas, Giacomo; Nahon, Laurent

    2014-10-28

    Polycyclic aromatic hydrocarbons (PAHs) are key species encountered in a large variety of environments such as the Interstellar Medium (ISM) and in combustion media. Their UV spectroscopy and photodynamics in neutral and cationic forms are important to investigate in order to learn about their structure, formation mechanisms, and reactivity. Here, we report an experimental photoelectron-photoion coincidence study of a prototypical PAH molecule, coronene, and its small clusters, in a molecular beam using the vacuum ultraviolet (VUV) photons provided by the SOLEIL synchrotron facility. Mass-selected high resolution threshold photoelectron (TPES) and total ion yield spectra were obtained and analyzed in detail. Intense series of autoionizing resonances have been characterized as originating from the monomer, dimer, and trimer neutral species, which may be used as spectral fingerprints for their detection in the ISM by VUV absorption spectroscopy. Finally, a full description of the electronic structure of the monomer cation was made and discussed in detail in relation to previous spectroscopic optical absorption data. Tentative vibrational assignments in the near-threshold TPES spectrum of the monomer have been made with the support of a theoretical approach based on density functional theory. PMID:25362317

  3. Effect of Trimeric Myricetin Rhamnoside (TMR) in Carrageenan-induced Inflammation and Caecal Ligation and Puncture-induced Lung Oxidative Stress in Mice.

    Science.gov (United States)

    Latief, Najeeb; Anand, Shikha; Lingaraju, Madhu Cholenahalli; Balaganur, Venkanna; Pathak, Nitya Nand; Kalra, Jaspreet; Kumar, Dinesh; Bhadoria, Brijesh K; Tandan, Surendra Kumar

    2015-11-01

    The Eugenia jambolana is used in folklore medicine. Leaves of E. jambolana contain flavonoids as their active constituents which possess in vitro antiinflammatory, antioxidant and the antimicrobial activity. The aim of the present study was to investigate the antiinflammatory and antioxidant effects of a flavonoid glucoside, trimeric myricetin rhamnoside (TMR) isolated from leaves of E. jambolana. TMR was studied for antiinflammatory activity in carrageenan-induced hind paw oedema and antioxidant activity in lung by caecal ligation and puncture (CLP)-induced sepsis in mice. Results of the present study indicated that TMR significantly attenuated the oedema, myeloperoxidase (MPO), cytokines and prostaglandin levels in the paw after 5 h of carrageenan injection as compared to vehicle control. It also reduced the lung MPO, lipid peroxides, and serum nitrite plus nitrate levels and increased lung reduced glutathione levels 20 h of CLP as compared to vehicle control. Thus the results of this study concluded that the TMR appears to have potential benefits in diseases that are mediated by both inflammation and oxidative stress and support the pharmacological basis of use of E. jambolana plant as traditional herbal medicine for the treatment of inflammatory diseases. PMID:26343251

  4. The molecular dynamic study of anharmonic effects at Cu(111) and Ag(111) surfaces in the presence of Cu- and Ag-trimer island

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Zulfiqar Ali [Department of Physics, Hazara University, Mansehra 21300 (Pakistan); Hayat, Sardar Sikandar, E-mail: sikandariub@yahoo.com [Department of Physics, Hazara University, Mansehra 21300 (Pakistan); Department of Physics, The Islamia University of Bahawalpur, Bahawalpur 63120 (Pakistan); Rehman, Z. [Department of Physics, Hazara University, Mansehra 21300 (Pakistan); Bouafia, Farida [LMPM, Mechanical Engineering Department, University of Sidi Bel Abbes, Sidi Bel Abbes 22000 (Algeria)

    2014-05-01

    The molecular dynamics (MD) technique based on semi-empirical potentials, is used to carry out the diffusion of Cu- and Ag-trimer on Cu- and Ag(111) surface at 300, 500 and 700 K temperatures. The constant energy MD simulation elaborates the anharmonic effects at the surface such as fissures, dislocations and vacancy creation, in the presence of island. The fissures and dislocations formed are in the range of 1.5–4 Å and 1–7 Å, respectively, from the island's position. The Cu and Ag islands both diffuse easily on Cu(111) surface, manipulate that the trend of diffusion is faster on Cu surface as compared to Ag surface. The process of breaking and opening of the island has also been observed. Moreover, a surface atom popped-up at 700 K by creating a vacancy near the Cu island on Ag surface. The rate of diffusion increases with the increase in temperature, both for homo- and hetero-cases.

  5. Transepithelial permeability studies of flavan-3-ol-C-glucosides and procyanidin dimers and trimers across the Caco-2 cell monolayer.

    Science.gov (United States)

    Hemmersbach, Sarah; Brauer, Susanne S; Hüwel, Sabine; Galla, Hans-Joachim; Humpf, Hans-Ulrich

    2013-08-21

    In this study the permeability of two flavanol-C-glucosides (FCglcs) and five dimeric and trimeric flavan-3-ols, namely, procyanidins (PCs), was investigated with the human colon carcinoma cell line (Caco-2) model. These compounds can be found especially in cocoa, and they are of great interest due to their assumed beneficial health effects. Transepithelial electrical resistance (TEER) and capacitance were measured online with a CellZscope device prior to and during the whole experiment to guarantee the maintenance of the barrier properties. The transport experiments with pure, single compounds (50-300 μM) from apical to basolateral side showed slight permeation of PCs A2, B2, and B5 and cinnamtannin B1 (CB1) as well as (-)-catechin-6-C-glucoside (C6Cglc) and (-)-catechin-8-C-glucoside (C8Cglc) of about 0.02-0.2% after 24 h. Transport of PC C1 could not be detected. Inhibition of P-glycoprotein (Pgp) increased the permeation of PC B2 and CB1 to the basolateral side, which indicates that Pgp counteracts the transport of these compounds. Metabolites (epicatechin, 3'- and 4'-O-epicatechin) in very small amounts were detectable only for PC B2. These are the first data concerning the permeability of flavan-3-ol-C-glucosides across the Caco-2 cell monolayer. PMID:23885956

  6. Di-tyrosine cross-link decreases the collisional cross-section of aβ peptide dimers and trimers in the gas phase: an ion mobility study.

    Directory of Open Access Journals (Sweden)

    Ewa Sitkiewicz

    Full Text Available Oligomeric forms of Aβ peptide are most likely the main synaptotoxic and neurotoxic agent in Alzheimer's disease. Toxicity of various Aβ oligomeric forms has been confirmed in vivo and also in vitro. However, in vitro preparations were found to be orders of magnitude less toxic than oligomers obtained from in vivo sources. This difference can be explained by the presence of a covalent cross-link, which would stabilize the oligomer. In the present work, we have characterized the structural properties of Aβ dimers and trimers stabilized by di- and tri-tyrosine cross-links. Using ion mobility mass spectrometry we have compared the collisional cross-section of non-cross-linked and cross-linked species. We have found that the presence of cross-links does not generate new unique forms but rather shifts the equilibrium towards more compact oligomer types that can also be detected for non-cross-linked peptide. In consequence, more extended forms, probable precursors of off-pathway oligomeric species, become relatively destabilized in cross-linked oligomers and the pathway of oligomer evolution becomes redirected towards fibrillar structures.

  7. Generation of a soluble recombinant trimeric form of bovine CD40L and its potential use as a vaccine adjuvant in cows.

    Science.gov (United States)

    Pujol, Julien; Bouillenne, Fabrice; Farnir, Frédéric; Dufrasne, Isabelle; Mainil, Jacques; Galleni, Moreno; Lekeux, Pierre; Bureau, Fabrice; Fiévez, Laurence

    2015-11-15

    Vaccination is the most cost-effective way to control infectious diseases in cattle. However, many infectious diseases leading to severe economical losses worldwide still remain for which a really effective and safe vaccine is not available. These diseases are most often due to intracellular pathogens such as bacteria or viruses, which are, by their localization, protected from antibiotics and/or CD4(+) T cell-dependent humoral responses. We therefore postulated that strategies leading to induction of not only CD4(+) T cell responses but also CD8(+) cytotoxic T lymphocyte (CTL) responses against infected cells should be privileged in the development of new vaccines against problematic intracellular pathogens in bovines. CD40 signaling in antigen-presenting cells may lead to the induction of robust CD4-independent CTL responses and several studies, especially in mice, have used CD40 stimulation to promote CD8(+) T cell-mediated immunity. For example, we have recently shown that immunization of mice with heat-killed Staphylococcus aureus (HKSA) and agonistic anti-CD40 monoclonal antibodies elicits strong CTL responses capable of protecting mice from subsequent staphylococcal mastitis. Unfortunately, there is at present no tool available to efficiently stimulate CD40 in cattle. In this study, we therefore first produced a soluble recombinant trimeric form of the natural bovine CD40 ligand (sboCD40LT). We then observed that sboCD40LT was able to potently stimulate bovine cells in vitro. Finally, we provide evidence that immunization of cows with sboCD40LT combined with HKSA was able to significantly increase the number of both HKSA-specific CD4(+) and CD8(+) T cells in the draining lymph nodes. In conclusion, we suggest that this new molecular tool could help in the development of vaccine strategies against bovine diseases caused by intracellular pathogens. PMID:26553560

  8. Novel methods for configuration interaction and orbital optimization for wave functions containing non-orthogonal orbitals with applications to the chromium dimer and trimer.

    Science.gov (United States)

    Olsen, Jeppe

    2015-09-21

    A novel algorithm for performing configuration interaction (CI) calculations using non-orthogonal orbitals is introduced. In the new algorithm, the explicit calculation of the Hamiltonian matrix is replaced by the direct evaluation of the Hamiltonian matrix times a vector, which allows expressing the CI-vector in a bi-orthonormal basis, thereby drastically reducing the computational complexity. A new non-orthogonal orbital optimization method that employs exponential mappings is also described. To allow non-orthogonal transformations of the orbitals, the standard exponential mapping using anti-symmetric operators is supplemented with an exponential mapping based on a symmetric operator in the active orbital space. Expressions are obtained for the orbital gradient and Hessian, which involve the calculation of at most two-body density matrices, thereby avoiding the time-consuming calculation of the three- and four-body density matrices of the previous approaches. An approach that completely avoids the calculation of any four-body terms with limited degradation of convergence is also devised. The novel methods for non-orthogonal configuration interaction and orbital optimization are applied to the chromium dimer and trimer. For internuclear distances that are typical for chromium clusters, it is shown that a reference configuration consisting of optimized singly occupied active orbitals is sufficient to give a potential curve that is in qualitative agreement with complete active space self-consistent field (CASSCF) calculations containing more than 500 × 10(6) determinants. To obtain a potential curve that deviates from the CASSCF curve by less than 1 mHartree, it is sufficient to add single and double excitations out from the reference configuration. PMID:26395682

  9. Conformation-specific antibodies targeting the trimer-of-hairpins motif of the human T-cell leukemia virus type 1 transmembrane glycoprotein recognize the viral envelope but fail to neutralize viral entry.

    Science.gov (United States)

    Mirsaliotis, Antonis; Nurkiyanova, Kulpash; Lamb, Daniel; Woof, Jenny M; Brighty, David W

    2007-06-01

    Human T-cell leukemia virus type 1 (HTLV-1) entry into cells is dependent upon the viral envelope glycoprotein-catalyzed fusion of the viral and cellular membranes. Following receptor activation of the envelope, the transmembrane glycoprotein (TM) is thought to undergo a series of fusogenic conformational transitions through a rod-like prehairpin intermediate to a compact trimer-of-hairpins structure. Importantly, synthetic peptides that interfere with the conformational changes of TM are potent inhibitors of membrane fusion and HTLV-1 entry, suggesting that TM is a valid target for antiviral therapy. To assess the utility of TM as a vaccine target and to explore further the function of TM in HTLV-1 pathogenesis, we have begun to examine the immunological properties of TM. Here we demonstrate that a recombinant trimer-of-hairpins form of the TM ectodomain is strongly immunogenic. Monoclonal antibodies raised against the TM immunogen specifically bind to trimeric forms of TM, including structures thought to be important for membrane fusion. Importantly, these antibodies recognize the envelope on virally infected cells but, surprisingly, fail to neutralize envelope-mediated membrane fusion or infection by pseudotyped viral particles. Our data imply that, even in the absence of overt membrane fusion, there are multiple forms of TM on virally infected cells and that some of these display fusion-associated structures. Finally, we demonstrate that many of the antibodies possess the ability to recruit complement to TM, suggesting that envelope-derived immunogens capable of eliciting a combination of neutralizing and complement-fixing antibodies would be of value as subunit vaccines for intervention in HTLV infections. PMID:17376912

  10. Self-assembly of linear [Mn II 2 Mn III ] units with end-on azido bridges: the construction of a ferromagnetic chain using S T = 7 high-spin trimers

    KAUST Repository

    Jiang, Yuan

    2015-01-01

    © The Royal Society of Chemistry 2015. The controlled organization of high-spin complexes into 1D coordination polymers is a challenge in molecular magnetism. In this work, we report a ferromagnetic Mn trimer Mn3(HL)2(CH3OH)6(Br)4·Br·(CH3OH)21 (H2L = 2-[(9H-fluoren-9-yl)amino]propane-1,3-diol) with the ground spin state of ST = 7 that can be assembled into a one-dimensional coordination chain [Mn3(HL)2(CH3OH)2(Br)4(N3)(H2O)·CH3OH]2 using azido bridging ligands. Interestingly, the ferromagnetic nature of 1 is well retained in 2. However, due to the negligible magnetic anisotropy in 1, both 1 and 2 do not show slow-relaxation of magnetization, which indicates that during the process of molecular assembly not only the intratrimer magnetic interaction but also the magnetic anisotropy of the trimer can be reserved.

  11. Computational study on pyrolysis mechanism of anα,β-diether-type lignin trimer model compound%α,β-双醚型木质素三聚体模化物热解机理模拟计算

    Institute of Scientific and Technical Information of China (English)

    蒋晓燕; 陈晨; 董晓晨; 陆强; 董长青

    2015-01-01

    In order to understand the pyrolysis mechanism of lignin trimer, 4-(1,2-diphenoxy)-propylphenol was selected as lignin trimer model compound containing both β-O-4 and α-O-4 linkages, and its pyrolysis processes were theoretically investigated by employing density functional theory method at M06-2X level with 6-31++G(d,p) basis set. The equilibrium geometries of the reactant, intermediates, transition states and products in the pyrolysis processes were fully optimized. The activation energy in each pyrolysis pathway was calculated. Analyses were performed to reveal the interaction of theβ-O-4 andα-O-4 linkages in their cleavages, as well as the overall pyrolytic mechanisms and the pathways of product formation. The calculation results indicated for the 6 primary homolytic ways of the lignin trimer model compound, and the bond dissociation energies were in the order of Cα-Otrimer model compound, while the homolytic cleavages of Cβ-O and Cα-Cβbonds were competitive pyrolysis reactions. Theβ-O-4 andα-O-4 linkages had little interaction effects in their primary cleavage reactions, because the bond dissociation energies of Cα-O and Cβ-O in the lignin trimer model compound were similar to those of the corresponding lignin dimer model compounds. However, after the initial cleavage of theα-O-4 (β-O-4) linkage, the formed intermediate had significantly reduced bond dissociation energy for the further cleavage of theβ-O-4 (α-O-4) linkage. Based on the energy barrier of each reaction pathway for the primary homolytic cleavage of Cα-O bond, the major pyrolytic products of the model compound included phenol, 4-propenylphenol, 4-allyphenol, and dimer compound with double bonds (the

  12. High frequency of transmitted HIV-1 Gag HLA class I-driven immune escape variants but minimal immune selection over the first year of clade C infection.

    Directory of Open Access Journals (Sweden)

    Kamini Gounder

    Full Text Available In chronic HIV infection, CD8+ T cell responses to Gag are associated with lower viral loads, but longitudinal studies of HLA-restricted CD8+ T cell-driven selection pressure in Gag from the time of acute infection are limited. In this study we examined Gag sequence evolution over the first year of infection in 22 patients identified prior to seroconversion. A total of 310 and 337 full-length Gag sequences from the earliest available samples (median = 14 days after infection [Fiebig stage I/II] and at one-year post infection respectively were generated. Six of 22 (27% individuals were infected with multiple variants. There was a trend towards early intra-patient viral sequence diversity correlating with viral load set point (p = 0.07, r = 0.39. At 14 days post infection, 59.7% of Gag CTL epitopes contained non-consensus polymorphisms and over half of these (35.3% comprised of previously described CTL escape variants. Consensus and variant CTL epitope proportions were equally distributed irrespective of the selecting host HLA allele and most epitopes remained unchanged over 12 months post infection. These data suggest that intrapatient diversity during acute infection is an indicator of disease outcome. In this setting, there is a high rate of transmitted CTL escape variants and limited immune selection in Gag during the first year of infection. These data have relevance for vaccine strategies designed to elicit effective CD8+ T cell immune responses.

  13. Ab initio calculation on the analytic potential energy functions for the state a3∑u+ and the state b3∏u of spin-aligned trimer 7Li2

    Institute of Scientific and Technical Information of China (English)

    Shi De-Heng; Sun Jin-Feng; Yang Xiang-Dong; Zhu Zun-Lue; Liu Yu-Fang

    2005-01-01

    The energies, equilibrium geometries and harmonic frequencies of the triplet excited states (a3∑u+ and b3∏u) of spin-aligned trimer 7Li2 are firstly calculated by using a symmetry adapted cluster-configuration interaction method.The potential curves for the two excited states have least squares fitted by the Murrell-Sorbie function. The spectroscopic data (Be, αe, ωe, and ωeχe) and the force constants (f2, f3 and f4) are calculated. It is found that the spin-aligned triplet excited state b3∏u is more stable than the ground state X1∑g+, and that the Murrell-Sorbie function form is suitable not only for the ground state but also for the spin-aligned triplet excited states. Comparison between the theoretical determinations of dissociation energies, equilibrium interatomic distances and harmonic frequencies with the agreement between theories and experiments.

  14. Hepatitis B virus core antigen epitopes presented by HLA-A2 single-chain trimers induce functional epitope-specific CD8+ T-cell responses in HLA-A2.1/Kb transgenic mice.

    Science.gov (United States)

    Zhang, Yuxia; Li, Shu; Shan, Ming; Pan, Xuwen; Zhuang, Ke; He, Lihua; Gould, Keith; Tien, Po

    2007-05-01

    The potency of CD8+ cytotoxic T lymphocyte (CTL) responses toward core antigen has been shown to affect the outcomes of hepatitis B virus (HBV) infection. Since single-chain trimers (SCT) composed of peptide epitope beta2-microglobulin (beta2m) and major histocompatibility complex (MHC) class I heavy chain covalently linked together in a single molecule have been shown to stimulate efficient CTL responses, we investigated the properties of human leucocyte antigen (HLA)-A2 SCTs encoding the HBV core antigen (HBcAg) epitopes C(18-27) and C(107-115). Transfection of NIH-3T3 cells with pcDNA3.0-SCT-C(18-27) and SCT-C(107-115) leads to stable presentation of HBcAg epitopes at the cell surface. HLA-A2.1/Kb transgenic mice vaccinated with the SCT constructs, either as a DNA vaccine alone or followed by a boost with recombinant vaccinia virus, were shown to generate HBcAg-specific CTL responses by enzyme-linked immunospot assay (ELISPOT) and in vitro interferon-gamma release experiments. HBcAg-specific CTLs from vaccinated HLA-A2.1/Kb transgenic mice were able to inhibit HBV surface and e antigen expression as indicated by HepG2.2.15 cells. Our data indicate that a DNA vaccine encoding a human HLA-A2 SCT with HBV epitopes can lead to stable, enhanced HBV core antigen presentation, and may be useful for the control of HBV infection in HLA-A2-positive HBV carriers. PMID:17244158

  15. Immunization with the Haemophilus ducreyi trimeric autotransporter adhesin DsrA with alum, CpG or imiquimod generates a persistent humoral immune response that recognizes the bacterial surface.

    Science.gov (United States)

    Samo, Melissa; Choudhary, Neelima R; Riebe, Kristina J; Shterev, Ivo; Staats, Herman F; Sempowski, Gregory D; Leduc, Isabelle

    2016-02-24

    The Ducreyi serum resistance A (DsrA) protein of Haemophilus ducreyi belongs to a large family of multifunctional outer membrane proteins termed trimeric autotransporter adhesins responsible for resistance to the bactericidal activity of human complement (serum resistance), agglutination and adhesion. The ability of DsrA to confer serum resistance and bind extracellular matrix proteins lies in its N-terminal passenger domain. We have previously reported that immunization with a recombinant form of the passenger domain of DsrA, rNT-DsrA, in complete/incomplete Freund's adjuvant, protects against a homologous challenge in swine. We present herein the results of an immunogenicity study in mice aimed at investigating the persistence, type of immune response, and the effect of immunization route and adjuvants on surrogates of protection. Our results indicate that a 20 μg dose of rNT-DsrA administered with alum elicited antisera with comparable bacterial surface reactivity to that obtained with complete/incomplete Freund's adjuvant. At that dose, high titers and bacterial surface reactivity persisted for 211 days after the first immunization. Administration of rNT-DsrA with CpG or imiquimod as adjuvants elicited a humoral response with similar quantity and quality of antibodies (Abs) as seen with Freund's adjuvant. Furthermore, intramuscular administration of rNT-DsrA elicited high-titer Abs with significantly higher reactivity to the bacterial surface than those obtained with subcutaneous immunization. All rNT-DsrA/adjuvant combinations tested, save CpG, elicited a Th2-type response. Taken together, these findings show that a 20 μg dose of rNT-DsrA administered with the adjuvants alum, CpG or imiquimod elicits high-quality Abs with reactivity to the bacterial surface that could protect against an H. ducreyi infection. PMID:26812077

  16. Identification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41.

    Directory of Open Access Journals (Sweden)

    Mei-Yun Zhang

    Full Text Available Identification of broadly cross-reactive HIV-1-neutralizing antibodies (bnAbs may assist vaccine immunogen design. Here we report a novel human monoclonal antibody (mAb, designated m43, which co-targets the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein (Env. M43 bound to recombinant gp140 s from various primary isolates, to membrane-associated Envs on transfected cells and HIV-1 infected cells, as well as to recombinant gp120 s and gp41 fusion intermediate structures containing N-trimer structure, but did not bind to denatured recombinant gp140 s and the CD4 binding site (CD4bs mutant, gp120 D368R, suggesting that the m43 epitope is conformational and overlaps the CD4bs on gp120 and the N-trimer structure on gp41. M43 neutralized 34% of the HIV-1 primary isolates from different clades and all the SHIVs tested in assays based on infection of peripheral blood mononuclear cells (PBMCs by replication-competent virus, but was less potent in cell line-based pseudovirus assays. In contrast to CD4, m43 did not induce Env conformational changes upon binding leading to exposure of the coreceptor binding site, enhanced binding of mAbs 2F5 and 4E10 specific for the membrane proximal external region (MPER of gp41 Envs, or increased gp120 shedding. The overall modest neutralization activity of m43 is likely due to the limited binding of m43 to functional Envs which could be increased by antibody engineering if needed. M43 may represent a new class of bnAbs targeting conformational epitopes overlapping structures on both gp120 and gp41. Its novel epitope and possibly new mechanism(s of neutralization could helpdesign improved vaccine immunogens and candidate therapeutics.

  17. Monomeric, trimeric, and tetrameric transition metal complexes (Mn, Fe, Co) containing N,N-bis(2-pyridylmethyl)-2-aminoethanol/-ate: preparation, crystal structure, molecular magnetism and oxidation catalysis.

    Science.gov (United States)

    Shin, Jong Won; Rowthu, Sankara Rao; Hyun, Min Young; Song, Young Joo; Kim, Cheal; Kim, Bong Gon; Min, Kil Sik

    2011-06-01

    The reaction of N,N-bis(2-pyridylmethyl)-2-aminoethanol (bpaeOH), NaSCN/NaN(3), and metal (M) ions [M = Mn(II), Fe(II/III), Co(II)] in MeOH, leads to the isolation of a series of monomeric, trimeric, and tetrameric metal complexes, namely [Mn(bpaeOH)(NCS)(2)] (1), [Mn(bpaeO)(N(3))(2)] (2), [Fe(bpaeOH)(NCS)(2)] (3), [Fe(4)(bpaeO)(2)(CH(3)O)(2)(N(3))(8)] (4), [Co(bpaeOH)(NCS)(2)] (5), and [Co(3)(bpaeO)(2)(NO(3))(N(3))(4)](NO(3)) (6). These compounds have been investigated by single crystal X-ray diffractometry and magnetochemistry. In complex 1 the Mn(II) is bonded to one bpaeOH and two thiocyanate ions, while in complex 2 it is coordinated to a deprotonated bpaeO(-) and two azide ions. The oxidation states of manganese ions are 2+ for 1 and 3+ for 2, respectively, indicating that the different oxidation states depend on the type of binding anions. The structures of monomeric iron(II) and cobalt(II) complexes 3 and 5 with two thiocyanate ions are isomorphous to that of 1. Compounds 1, 2, 3, and 5 exhibit high-spin states in the temperature range 5 to 300 K. 4 contains two different iron(III) ions in an asymmetric unit, one is coordinated to a deprotonated bpaeO(-), an azide ion, and a methoxy group, and the other is bonded to three azide ions and two oxygens from bpaeO(-) and a methoxy group. Two independent iron(III) ions in 4 form a tetranuclear complex by symmetry. 4 displays both ferromagnetic and antiferromagnetic couplings (J = 9.8 and -14.3 cm(-1)) between the iron(III) ions. 6 is a mixed-valence trinuclear cobalt complex, which is formulated as Co(III)(S = 0)-Co(II)(S = 3/2)-Co(III)(S = 0). The effective magnetic moment at room temperature corresponds to the high-spin cobalt(II) ion (∼4.27 μ(B)). Interestingly, 6 showed efficient catalytic activities toward various olefins and alcohols with modest to excellent yields, and it has been proposed that a high-valent Co(V)-oxo species might be responsible for oxygen atom transfer in the olefin epoxidation and

  18. HIV-1 Env DNA vaccine plus protein boost delivered by EP expands B- and T-cell responses and neutralizing phenotype in vivo.

    Directory of Open Access Journals (Sweden)

    Kar Muthumani

    Full Text Available An effective HIV vaccine will most likely require the induction of strong T-cell responses, broadly neutralizing antibodies (bNAbs, and the elicitation of antibody-dependent cellular cytotoxicity (ADCC. Previously, we demonstrated the induction of strong HIV/SIV cellular immune responses in macaques and humans using synthetic consensus DNA immunogens delivered via adaptive electroporation (EP. However, the ability of this improved DNA approach to prime for relevant antibody responses has not been previously studied. Here, we investigate the immunogenicity of consensus DNA constructs encoding gp140 sequences from HIV-1 subtypes A, B, C and D in a DNA prime-protein boost vaccine regimen. Mice and guinea pigs were primed with single- and multi-clade DNA via EP and boosted with recombinant gp120 protein. Sera were analyzed for gp120 binding and induction of neutralizing antibody activity. Immunization with recombinant Env protein alone induced low-titer binding antibodies with limited neutralization breath. In contrast, the synthetic DNA prime-protein boost protocol induced significantly higher antibody binding titers. Furthermore, sera from DNA prime-protein boost groups were able to neutralize a broader range of viruses in a panel of tier 1 clade B viruses as well as multiple tier 1 clade A and clade C viruses. Further investigation of synthetic DNA prime plus adaptive EP plus protein boost appears warranted.

  19. A mixed Ni(II) ionic complex containing V-shaped water trimer: Synthesis, spectral, structural and thermal properties of {[Ni(2,2′-bpy)3][Ni(2-cpida)(2,2′ -bpy)]} (ClO4).3H2O

    Indian Academy of Sciences (India)

    Nallasamy Palanisami; Kabali Senthilkumar; Mohan Gopalakrishnan; Il-Shik Moon

    2015-05-01

    A mixed Ni(II) ionic complex of {[Ni(2,2′-bpy)3][Ni(2-cpida)(2,2′-bpy)]}(ClO4).3H2O (1) (2-H3cpida = N-(2-carboxyphenyl)iminodiacetic acid, 2,2′-bpy = 2,2′-bipyridyl) has been synthesized and characterized by infrared, ultraviolet and fluorescence spectroscopy, elemental and thermogravimetric analysis. The molecular structure of compound 1, as determined by single-crystal X-ray diffraction studies, showed all the three carboxylate groups are in monodendate mode. Compound 1 consists of a discrete mononuclear [Ni(2,2′-bpy)3]2+ cation, a [Ni(2-cpida)(2,2′-bpy)]− anion, a ClO$^{−}_{4}$ anion and three lattice water molecules. The H-bonding interaction between three lattice water molecule forms a V-shaped trimer (H2O)3 which gives rise to a 1-D polymeric structure in the solid state.

  20. Expression of a single-chain trimer of MHC restricted HBsAg CTL epitope using adenovirus vector containing GFP-report gene%采用绿色荧光蛋白腺病毒载体表达HBsAgCTL优势表位肽MHC单链三聚体

    Institute of Scientific and Technical Information of China (English)

    陈心春; 刘威龙; 杨桂林; 刘勇军; 朱秀云; 张红梅; 周伯平; Lybarger Lonnie

    2009-01-01

    目的 采用携带GFP报告基因腺病毒载体表达HBsAg细胞毒性T细胞(CIL)表位MHC单链三聚体,为增强HBV特异性免疫提供新方法.方法 构建小鼠MHC Ⅰ类分子(H-2Ld)限制的HBsAg优势CTL表位肽与MHCⅠ类分子重链(Ld)和β2M链(β2-microglobulin,β2微球蛋白)的单链三聚体(HBsAg-SCT).并将HBsAg-SCT亚克隆到GFP标记腺病毒载体,以HBsAg和OVA-SCT作为对照,转染293A细胞,包装产生携带HBsAs-SCT,HBsAg和OVA-SCT的重组腺病毒.结果 经双酶切和克隆测序鉴定,HBsAg-SCT能成功克隆到编码GFP标记的腺病毒载体,通过荧光显微镜观察到转染的293A细胞含有绿色荧光素蛋白.通过Western Blot进一步证实表达的重组蛋白HBsAg-SCT能与抗-腿抗体发生反应.结论 编码HBsAg-SCT的荧光蛋白腺病毒载体成功构建,并能在293A细胞中完整包装成重组腺病毒颗粒.%Objective To generate a recombinant Adenovh'us encoding a GFP (green fluorescent protein)-report gene and a single-chain trimer of MHC restricted HBsAg CTL epitope. Methods An oligonucleotide encoding H-2Ld restricted HBsAg CTL epitopo was synthesized and fused with H-2Ld DNA molecule to construct the eukaryotic expression vector carrying the HBsAg-SCT gene. The HBsAg-SCT gene was subcloned into a GFP adenovirus expression vector,which was transfeeted into Ad293 cells for packaging and amplification of recombinant adenovirus encoding HBsAg-SCT. Results HBsAg-SCT has been cloned into an adenovirus vector encoding GFP report gene successfully as confirmed by double enzyme digestion and direct sequencing. HBsAg-SCT was expressed by infected Ad293 ceils demonstrated by western blot assay. Conclusion A recombinant adenovirus expressing HBsAg-SCT and green fluorescent protein report gene has been generated.

  1. Sterically demanding aryloxides as supporting ligands in organoactinide chemistry. Synthesis, structural characterization, and reactivity of Th(O-2,6-t-Bu2C6H3)2(CH2SiMe3)2 and formation of the trimeric thorium hydride Th3H6(O-2,6-t-Bu2C6H3)6

    International Nuclear Information System (INIS)

    Reactions of ThBr4(THF)4 with 2 equiv of KOAr (Ar = 2,6-t-Bu2C6H3) produces the bis-(aryloxide) complex ThBr2(OAr)2(THF)2(1) in 67% yield. Alkylation of 1 with 2 equiv of Me3SiCH2MgCl allows the isolation of Th(OAr)2(CH2SiMe3)2 (2) in 61% yield. Thermolysis of 2 (benzene, 60 degree C, 36 h) in the presence of NEt3 results in the formation of the cyclometalated ligand redistribution product Th(OC6H3-t-BuCMe2CH2)(OAr)2 (3). Reaction of 2 with 1 equiv of 2,6-dimethylphenyl isocyanate leads to insertion into the Th-C bond to yield (ArO)2Th[C(=NR)CH2SiMe3] (CH2SiMe3) (4; R = 2,6-Me2C6H3). Aminolysis of 2 with 2 equiv of 2,6-diisopropylaniline allows the isolation of the bis(amido) species TH(OAr)2(NH-2,6-i-Pr2C6H3)2 (5) in 92% yield. 2 reacts with dihydrogen (1.5 atm) over a period of 7 days to form the trimeric dihydride complex Th3(μ3-H)2(μ2-H)4(OAr)6 (6). In the presence of 1 equiv of [HNMe2Ph][B(C6F5)4], 2 catalyzes the hydrogenation of 1-hexene (Nt = 1 h-1), while 6 is found to be a single-component catalyst for the analogous process (Nt = 3 h-1). Complexes 1-6 have been characterized by 1H NMR and IR spectroscopy, microanalysis, and, in the case of 2 and 6, by single-crystal X-ray diffraction studies. Results are presented in this paper. 45 refs., 2 figs., 5 tabs

  2. Photoabsorption spectrum of helium trimer cation—Theoretical modeling

    Energy Technology Data Exchange (ETDEWEB)

    Kalus, René [Centre of Excellence IT4Innovations and Department of Applied Mathematics, VSB-Technical University of Ostrava, 17. listopadu 15, 708 33 Ostrava (Czech Republic); Karlický, František [Regional Centre of Advanced Technologies and Materials and Department of Physical Chemistry, Faculty of Science, Palacký University, Tř. 17. listopadu 12, 771 46 Olomouc (Czech Republic); Lepetit, Bruno [Laboratoire Collisions Agrégats Réactivité, IRSAMC and UMR5589 du CNRS, Université de Toulouse, UPS, 118 route de Narbonne, 31062 Toulouse Cedex (France); Paidarová, Ivana [J. Heyrovský Institute of Physical Chemistry, ASCR, v.v.i., Dolejškova 3, 182 23 Praha (Czech Republic); Gadea, Florent Xavier [Laboratoire de Chimie et de Physique Quantiques, IRSAMC and UMR5626 du CNRS, Université de Toulouse, UPS, 118 route de Narbonne, 31062 Toulouse Cedex (France)

    2013-11-28

    The photoabsorption spectrum of He{sub 3}{sup +} is calculated for two semiempirical models of intracluster interactions and compared with available experimental data reported in the middle UV range [H. Haberland and B. von Issendorff, J. Chem. Phys. 102, 8773 (1995)]. Nuclear delocalization effects are investigated via several approaches comprising quantum samplings using either exact or approximate (harmonic) nuclear wavefunctions, as well as classical samplings based on the Monte Carlo methodology. Good agreement with the experiment is achieved for the model by Knowles et al., [Mol. Phys. 85, 243 (1995); Mol. Phys. 87, 827 (1996)] whereas the model by Calvo et al., [J. Chem. Phys. 135, 124308 (2011)] exhibits non-negligible deviations from the experiment. Predictions of far UV absorption spectrum of He{sub 3}{sup +}, for which no experimental data are presently available, are reported for both models and compared to each other as well as to the photoabsorption spectrum of He{sub 2}{sup +}. A simple semiempirical point-charge approximation for calculating transition probabilities is shown to perform well for He{sub 3}{sup +}.

  3. Viral aggregating and opsonizing activity in collectin trimers

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L; White, Mitchell R; Tecle, Tesfaldet;

    2010-01-01

    bovine serum collectin CL-46 induces aggregation of influenza A virus (IAV) and potently increases IAV uptake by neutrophils. CL-46-NCRD showed calcium-dependent and sugar-sensitive binding to both neutrophils and IAV. Replacement of specific residues of the CRD of human SP-D with those found in bovine...... serum collectins conferred opsonizing activity. The most effective substitution involved replacement of arginine 343 with valine (hSP-D-NCRD/R343V). hSP-D-NCRD/R343V greatly increased viral uptake by neutrophils and monocytes and also potentiated neutrophil respiratory burst responses. These effects...

  4. Photoabsorption spectrum of helium trimer cation--theoretical modeling.

    Science.gov (United States)

    Kalus, René; Karlický, František; Lepetit, Bruno; Paidarová, Ivana; Gadea, Florent Xavier

    2013-11-28

    The photoabsorption spectrum of He3(+) is calculated for two semiempirical models of intracluster interactions and compared with available experimental data reported in the middle UV range [H. Haberland and B. von Issendorff, J. Chem. Phys. 102, 8773 (1995)]. Nuclear delocalization effects are investigated via several approaches comprising quantum samplings using either exact or approximate (harmonic) nuclear wavefunctions, as well as classical samplings based on the Monte Carlo methodology. Good agreement with the experiment is achieved for the model by Knowles et al., [Mol. Phys. 85, 243 (1995); Mol. Phys. 87, 827 (1996)] whereas the model by Calvo et al., [J. Chem. Phys. 135, 124308 (2011)] exhibits non-negligible deviations from the experiment. Predictions of far UV absorption spectrum of He3(+), for which no experimental data are presently available, are reported for both models and compared to each other as well as to the photoabsorption spectrum of He2(+). A simple semiempirical point-charge approximation for calculating transition probabilities is shown to perform well for He3(+). PMID:24289357

  5. Photoabsorption spectrum of helium trimer cation—Theoretical modeling

    Czech Academy of Sciences Publication Activity Database

    Kalus, R.; Karlický, F.; Lepetit, B.; Paidarová, Ivana; Gadea, F. X.

    2013-01-01

    Roč. 139, č. 20 (2013), s. 204310. ISSN 0021-9606 Institutional support: RVO:61388955 Keywords : ab-initio calculations * gas ionic clusters * molecular dynamics Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.122, year: 2013

  6. Photoabsorption spectrum of helium trimer cation—Theoretical modeling

    Science.gov (United States)

    Kalus, René; Karlický, František; Lepetit, Bruno; Paidarová, Ivana; Gadea, Florent Xavier

    2013-11-01

    The photoabsorption spectrum of He_3^+ is calculated for two semiempirical models of intracluster interactions and compared with available experimental data reported in the middle UV range [H. Haberland and B. von Issendorff, J. Chem. Phys. 102, 8773 (1995)]. Nuclear delocalization effects are investigated via several approaches comprising quantum samplings using either exact or approximate (harmonic) nuclear wavefunctions, as well as classical samplings based on the Monte Carlo methodology. Good agreement with the experiment is achieved for the model by Knowles et al., [Mol. Phys. 85, 243 (1995); Knowles et al., Mol. Phys. 87, 827 (1996)] whereas the model by Calvo et al., [J. Chem. Phys. 135, 124308 (2011)] exhibits non-negligible deviations from the experiment. Predictions of far UV absorption spectrum of He_3^+, for which no experimental data are presently available, are reported for both models and compared to each other as well as to the photoabsorption spectrum of He_2^+. A simple semiempirical point-charge approximation for calculating transition probabilities is shown to perform well for He_3^+.

  7. Communication: Isotopic effects on tunneling motions in the water trimer

    Energy Technology Data Exchange (ETDEWEB)

    Videla, Pablo E. [Departamento de Química Inorgánica Analítica y Química-Física e INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, 1428 Buenos Aires (Argentina); Rossky, Peter J. [Department of Chemistry, Rice University, Houston, Texas 77251-1892 (United States); Laria, D., E-mail: dhlaria@cnea.gov.ar [Departamento de Química Inorgánica Analítica y Química-Física e INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, 1428 Buenos Aires (Argentina); Departamento de Física de la Materia Condensada, Comisión Nacional de Energía Atómica, Avenida Libertador 8250, 1429 Buenos Aires (Argentina)

    2016-02-14

    We present results of ring polymer molecular dynamics simulations that shed light on the effects of nuclear quantum fluctuations on tunneling motions in cyclic [H{sub 2}O]{sub 3} and [D{sub 2}O]{sub 3}, at the representative temperature of T = 75 K. In particular, we focus attention on free energies associated with two key isomerization processes: The first one corresponds to flipping transitions of dangling OH bonds, between up and down positions with respect to the O–O–O plane of the cluster; the second involves the interchange between connecting and dangling hydrogen bond character of the H-atoms in a tagged water molecule. Zero point energy and tunneling effects lead to sensible reductions of the free energy barriers. Due to the lighter nature of the H nuclei, these modifications are more marked in [H{sub 2}O]{sub 3} than in [D{sub 2}O]{sub 3}. Estimates of the characteristic time scales describing the flipping transitions are consistent with those predicted based on standard transition-state-approximation arguments.

  8. Communication: Isotopic effects on tunneling motions in the water trimer

    Science.gov (United States)

    Videla, Pablo E.; Rossky, Peter J.; Laria, D.

    2016-02-01

    We present results of ring polymer molecular dynamics simulations that shed light on the effects of nuclear quantum fluctuations on tunneling motions in cyclic [H2O]3 and [D2O]3, at the representative temperature of T = 75 K. In particular, we focus attention on free energies associated with two key isomerization processes: The first one corresponds to flipping transitions of dangling OH bonds, between up and down positions with respect to the O-O-O plane of the cluster; the second involves the interchange between connecting and dangling hydrogen bond character of the H-atoms in a tagged water molecule. Zero point energy and tunneling effects lead to sensible reductions of the free energy barriers. Due to the lighter nature of the H nuclei, these modifications are more marked in [H2O]3 than in [D2O]3. Estimates of the characteristic time scales describing the flipping transitions are consistent with those predicted based on standard transition-state-approximation arguments.

  9. A Trimeric Proanthocyanidin from the Bark of Acacia leucophloea Willd.

    Directory of Open Access Journals (Sweden)

    Sarfaraz Ahmed

    2014-05-01

    Full Text Available (–-Fisetinidol-(4α,8-[(–-fisetinidol-(4α,6 ]-(+-catechin ( 1 , a proanthocyanidin, was isolated from the bark of Acacia leucophloea . Its structure including absolute configuration was elucidated on the basis of spectroscopic analysis and chemical correlation . The 1H NMR spectrum of this compound, exhibiting exceptional complex signals attributable to rotational isomerism, and the reported data were obtained at elevated temperature in methyl ether acetate form. This work provided the 1H and 13C NMR assignments for 1 and its rotational isomer as the free phenolic form at ambient temperature for the first time. Compound 1 showed inhibitory activity against α-glucosidase type IV from Bacillus stearothermophilus with the IC 50 value of 102.3 μM.

  10. Communication: Isotopic effects on tunneling motions in the water trimer

    International Nuclear Information System (INIS)

    We present results of ring polymer molecular dynamics simulations that shed light on the effects of nuclear quantum fluctuations on tunneling motions in cyclic [H2O]3 and [D2O]3, at the representative temperature of T = 75 K. In particular, we focus attention on free energies associated with two key isomerization processes: The first one corresponds to flipping transitions of dangling OH bonds, between up and down positions with respect to the O–O–O plane of the cluster; the second involves the interchange between connecting and dangling hydrogen bond character of the H-atoms in a tagged water molecule. Zero point energy and tunneling effects lead to sensible reductions of the free energy barriers. Due to the lighter nature of the H nuclei, these modifications are more marked in [H2O]3 than in [D2O]3. Estimates of the characteristic time scales describing the flipping transitions are consistent with those predicted based on standard transition-state-approximation arguments

  11. Gamma irradiation study on barbituric acid and its phosphorus trimer

    International Nuclear Information System (INIS)

    Phosphorus tri barbiturate was synthesized from barbituric acid and structure was substantiated on the basis of microanalytical and spectroscopic techniques. The reactant and product were irradiated by gamma-rays and the ultraviolet measurements taken before and after irradiation were discussed. The effect of dose rate on UV absorption was found to be insignificant. The PH values were also measured before and after irradiation and the variation was correlated with the UV shifts at various concentrations of the aqueous solution of the compound. The results suggested, that the possible radiolysis decomposition site in the product is the carbon-phosphorus bond. The thermal analysis results were also studied

  12. The Trimeric Model: A New Model of Periodontal Treatment Planning

    OpenAIRE

    Azouni, Khalid G; Tarakji, Bassel

    2014-01-01

    Treatment of periodontal disease is a complex and multidisciplinary procedure, requiring periodontal, surgical, restorative, and orthodontic treatment modalities. Several authors attempted to formulate models for periodontal treatment that orders the treatment steps in a logical and easy to remember manner. In this article, we discuss two models of periodontal treatment planning from two of the most well-known textbook in the specialty of periodontics internationally. Then modify them to arri...

  13. Dimensional Effects on the Momentum distribution of Bosonic Trimer States

    DEFF Research Database (Denmark)

    F. Bellotti, F.; Frederico, T.; T. Yamashita, M.;

    2013-01-01

    The momentum distribution is a powerful probe of strongly-interacting systems that are expected to display universal behavior. This is contained in the contact parameters which relate few- and many-body properties. Here we consider a Bose gas in two dimensions and explicitly show that the two......-body contact parameter is universal and then demonstrate that the momentum distribution at next-to-leading order has a logarithmic dependence on momentum which is vastly different from the three-dimensional case. Based on this, we propose a scheme for measuring the effective dimensionality of a quantum many......-body system by exploiting the functional form of the momentum distribution....

  14. Human Antibodies that Recognize Novel Immunodominant Quaternary Epitopes on the HIV-1 Env Protein.

    Directory of Open Access Journals (Sweden)

    Mark D Hicar

    Full Text Available Numerous broadly neutralizing antibodies (Abs target epitopes that are formed or enhanced during mature HIV envelope formation (i.e. quaternary epitopes. Generally, it is thought that Env epitopes that induce broadly neutralizing Abs are difficult to access and poorly immunogenic because of the characteristic oligomerization, conformational flexibility, sequence diversity and extensive glycosylation of Env protein. To enhance for isolation of quaternary epitope-targeting Abs (QtAbs, we previously used HIV virus-like particles (VLPs to bind B cells from long-term non-progressor subjects to identify a panel of monoclonal Abs. When expressed as recombinant full-length Abs, a subset of these novel Abs exhibited the binding profiles of QtAbs, as they either failed to bind to monomeric Env protein or showed much higher affinity for Env trimers and VLPs. These QtAbs represented a significant proportion of the B-cell response identified with VLPs. The Ab genes of these clones were highly mutated, but they did not neutralize common HIV strains. We sought to further define the epitopes targeted by these QtAbs. Competition-binding and mapping studies revealed these Abs targeted four separate epitopes; they also failed to compete for binding by Abs to known major neutralizing epitopes. Detailed epitope mapping studies revealed that two of the four epitopes were located in the gp41 subunit of Env. These QtAbs bound pre-fusion forms of antigen and showed differential binding kinetics depending on whether oligomers were produced as recombinant gp140 trimers or as full-length Env incorporated into VLPs. Antigenic regions within gp41 present unexpectedly diverse structural epitopes, including these QtAb epitopes, which may be targeted by the naturally occurring Ab response to HIV infection.

  15. Human Antibodies that Recognize Novel Immunodominant Quaternary Epitopes on the HIV-1 Env Protein.

    Science.gov (United States)

    Hicar, Mark D; Chen, Xuemin; Sulli, Chidananda; Barnes, Trevor; Goodman, Jason; Sojar, Hakimuddin; Briney, Bryan; Willis, Jordan; Chukwuma, Valentine U; Kalams, Spyros A; Doranz, Benjamin J; Spearman, Paul; Crowe, James E

    2016-01-01

    Numerous broadly neutralizing antibodies (Abs) target epitopes that are formed or enhanced during mature HIV envelope formation (i.e. quaternary epitopes). Generally, it is thought that Env epitopes that induce broadly neutralizing Abs are difficult to access and poorly immunogenic because of the characteristic oligomerization, conformational flexibility, sequence diversity and extensive glycosylation of Env protein. To enhance for isolation of quaternary epitope-targeting Abs (QtAbs), we previously used HIV virus-like particles (VLPs) to bind B cells from long-term non-progressor subjects to identify a panel of monoclonal Abs. When expressed as recombinant full-length Abs, a subset of these novel Abs exhibited the binding profiles of QtAbs, as they either failed to bind to monomeric Env protein or showed much higher affinity for Env trimers and VLPs. These QtAbs represented a significant proportion of the B-cell response identified with VLPs. The Ab genes of these clones were highly mutated, but they did not neutralize common HIV strains. We sought to further define the epitopes targeted by these QtAbs. Competition-binding and mapping studies revealed these Abs targeted four separate epitopes; they also failed to compete for binding by Abs to known major neutralizing epitopes. Detailed epitope mapping studies revealed that two of the four epitopes were located in the gp41 subunit of Env. These QtAbs bound pre-fusion forms of antigen and showed differential binding kinetics depending on whether oligomers were produced as recombinant gp140 trimers or as full-length Env incorporated into VLPs. Antigenic regions within gp41 present unexpectedly diverse structural epitopes, including these QtAb epitopes, which may be targeted by the naturally occurring Ab response to HIV infection. PMID:27411063

  16. Theoretical study on the effects of the substituent groups on the homolysis of the ether bond in lignin trimer model compounds%取代基对木质素三聚体模型化合物醚键均裂反应影响的密度泛函理论研究

    Institute of Scientific and Technical Information of China (English)

    蒋晓燕; 陆强; 董晓晨; 胡斌; 董长青

    2016-01-01

    The homolytic bond dissociation energi es ( BDEs) of Cα-Oa nd Cβ-O bno ds in 27 lignin trimer model compounds were calculated by emplyo ing density functional theory methods at M062 X level with 6-31++G( d,p) basis set;the effcet s of vair ous subsit tune t groups( CH3 , CH2 OH and OCH3 )a t different positions on theB DE s of Cα-O and Cβ-O bonsd were invets igated.The results indicated ht at a sni gle methoxyl group at R2 or R3 has a minor influence on the BDE of Cβ-O bond, whereas two methoxyl groups at R2 and R3 lead to an obvious decrae se in the BDE of Cβ-O bond.The decrement in the BDE of Cβ-O bond fromt he methoxyl groups at R2 and R3 ac n be enah nced byt he mte hoxyl groups ta R4 and R5 , but si hardly influenced by thes ubstituent groups at R1 .Meanwhile, the BDE of Cα-O bond is gradually reduced when the H atoms at R4 and R5 are successively substituted with methoxyl groups; the decrement in the BDE of Cα-O bond from the methoxyl groups at R4 and R5 can be strengthened by the methoxyl groups at R2 and R3 .Furthermore, the methyl and hydroxymethyl groups at R1 can gradually increase the BDE of Cα-O bond and this effect is weakened when the H atoms at R2 and R3 are successively substituted with methoxyl groups.The methyl group at R1 has little influence on the BDE of Cβ-O bond, which is however dramatically increased by the hydroxymethyl group at R1 .%利用密度泛函理论M062 X/6-31++G( d,p)方法,对27种具有不同取代基(甲基、羟甲基和甲氧基)的木质素三聚体模型化合物的Cα-O和Cβ-O键均裂解离能进行了理论计算,探究了不同位置取代基对醚键解离能的影响规律。结果表明,当R2或R3位氢原子仅有一个被甲氧基取代时,Cβ-O键解离能变化很小;当R2、R3位氢原子均被甲氧基取代时,Cβ-O键解离能明显降低;且R4、R5位甲氧基能强化R2、R3位甲氧基对Cβ-O键解离能的降低程度,而不受R1

  17. Motif-Optimized Subtype A HIV Envelope-based DNA Vaccines Rapidly Elicit Neutralizing Antibodies When Delivered Sequentially

    Science.gov (United States)

    Pissani, Franco; Malherbe, Delphine C.; Robins, Harlan; DeFilippis, Victor R.; Park, Byung; Sellhorn, George; Stamatatos, Leonidas; Overbaugh, Julie; Haigwood, Nancy L.

    2012-01-01

    HIV-1 infection results in the development of a diverging quasispecies unique to each infected individual. Envelope (Env)-specific neutralizing antibodies (NAbs) typically develop over months to years after infection and initially are limited to the infecting virus. In some subjects, antibody responses develop that neutralize heterologous isolates (HNAbs), a phenomenon termed broadening of the NAb response. Studies of co-crystalized antibodies and proteins have facilitated the identification of some targets of broadly neutralizing monoclonal antibodies (NmAbs) capable of neutralizing many or most heterologous viruses; however, the ontogeny of these antibodies in vivo remains elusive. We hypothesize that Env protein escape variants stimulate broad NAb development in vivo and could generate such NAbs when used as immunogens. Here we test this hypothesis in rabbits using HIV Env vaccines featuring: (1) use of individual quasispecies env variants derived from an HIV-1 subtype A-infected subject exhibiting high levels of NAbs within the first year of infection that increased and broadened with time; (2) motif optimization of envs to enhance in vivo expression of DNA formulated as vaccines; and (3) a combined DNA plus protein boosting regimen. Vaccines consisted of multiple env variants delivered sequentially and a simpler regimen that utilized only the least and most divergent clones. The simpler regimen was as effective as the more complex approach in generating modest HNAbs and was more efficient when modified, motif-optimized DNA was used in combination with trimeric gp140 protein. This is a rationally designed strategy that facilitates future vaccine design by addressing the difficult problem of generating HNAbs to HIV by empirically testing the immunogenicity of naturally occurring quasispecies env variants. PMID:22749601

  18. Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1

    Science.gov (United States)

    Pollara, Justin; McGuire, Erin; Fouda, Genevieve G.; Rountree, Wes; Eudailey, Josh; Overman, R. Glenn; Seaton, Kelly E.; Deal, Aaron; Edwards, R. Whitney; Tegha, Gerald; Kamwendo, Deborah; Kumwenda, Jacob; Nelson, Julie A. E.; Liao, Hua-Xin; Brinkley, Christie; Denny, Thomas N.; Ochsenbauer, Christina; Ellington, Sascha; King, Caroline C.; Jamieson, Denise J.; van der Horst, Charles; Kourtis, Athena P.; Tomaras, Georgia D.; Ferrari, Guido

    2015-01-01

    ABSTRACT Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatally, even in the absence of maternal antiretroviral therapy. This suggests that immune factors in breast milk of HIV-1-infected mothers help to limit vertical transmission. We compared the HIV-1 envelope-specific breast milk and plasma antibody responses of clade C HIV-1-infected postnatally transmitting and nontransmitting mothers in the control arm of the Malawi-based Breastfeeding Antiretrovirals and Nutrition Study using multivariable logistic regression modeling. We found no association between milk or plasma neutralization activity, antibody-dependent cell-mediated cytotoxicity, or HIV-1 envelope-specific IgG responses and postnatal transmission risk. While the envelope-specific breast milk and plasma IgA responses also did not reach significance in predicting postnatal transmission risk in the primary model after correction for multiple comparisons, subsequent exploratory analysis using two distinct assay methodologies demonstrated that the magnitudes of breast milk total and secretory IgA responses against a consensus HIV-1 envelope gp140 (B.con env03) were associated with reduced postnatal transmission risk. These results suggest a protective role for mucosal HIV-1 envelope-specific IgA responses in the context of postnatal virus transmission. This finding supports further investigations into the mechanisms by which mucosal IgA reduces risk of HIV-1 transmission via breast milk and into immune interventions aimed at enhancing this response. IMPORTANCE Infants born to HIV-1-infected mothers are repeatedly exposed to the virus in breast milk. Remarkably, the transmission rate is low, suggesting that immune factors in the breast milk of HIV-1-infected mothers help to limit transmission. We compared the antibody

  19. Postionization fragmentation of rare-gas trimers revisited with new theoretical approaches

    Czech Academy of Sciences Publication Activity Database

    Janeček, I.; Cintavá, S.; Hrivňák, D.; Kalus, R.; Fárník, Michal; Gadea, F. X.

    2009-01-01

    Roč. 131, č. 11 (2009), s. 114306. ISSN 0021-9606 R&D Projects: GA AV ČR IAA401870702 Institutional research plan: CEZ:AV0Z40400503 Keywords : molecular dynamics * electron-impact * physical properties Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.093, year: 2009

  20. The DNA polymerase III holoenzyme contains γ and is not a trimeric polymerase

    Science.gov (United States)

    Dohrmann, Paul R.; Correa, Raul; Frisch, Ryan L.; Rosenberg, Susan M.; McHenry, Charles S.

    2016-01-01

    There is widespread agreement that the clamp loader of the Escherichia coli replicase has the composition DnaX3δδ’χψ. Two DnaX proteins exist in E. coli, full length τ and a truncated γ that is created by ribosomal frameshifting. τ binds DNA polymerase III tightly; γ does not. There is a controversy as to whether or not DNA polymerase III holoenzyme (Pol III HE) contains γ. A three-τ form of Pol III HE would contain three Pol IIIs. Proponents of the three-τ hypothesis have claimed that γ found in Pol III HE might be a proteolysis product of τ. To resolve this controversy, we constructed a strain that expressed only τ from a mutated chromosomal dnaX. γ containing a C-terminal biotinylation tag (γ-Ctag) was provided in trans at physiological levels from a plasmid. A 2000-fold purification of Pol III* (all Pol III HE subunits except β) from this strain contained one molecule of γ-Ctag per Pol III* assembly, indicating that the dominant form of Pol III* in cells is Pol III2τ2 γδδ’χψ. Revealing a role for γ in cells, mutants that express only τ display sensitivity to ultraviolet light and reduction in DNA Pol IV-dependent mutagenesis associated with double-strand-break repair, and impaired maintenance of an F’ episome. PMID:26786318

  1. Trimerization of apolipoprotein A-I retards plasma clearance and preserves antiatherosclerotic properties

    DEFF Research Database (Denmark)

    Graversen, Jonas Heilskov; Laurberg, Jacob Marsvin; Andersen, Mikkel Holmen;

    2008-01-01

    An increased plasma level of the major high-density lipoprotein (HDL) component, apolipoprotein A-I (apoA-I) is the aim of several therapeutic strategies for combating atherosclerotic disease. HDL therapy by direct intravenous administration of apoA-I is a plausible way; however, a fast renal...

  2. Type XVII collagen (BP180) and LAD-1 are present as separate trimeric complexes

    NARCIS (Netherlands)

    Pas, HH; Kloosterhuis, GJ; Nijenhuis, Albertine; de Jong, MCJM; van der Meer, JB; Jonkman, MF

    1999-01-01

    This study characterized the high molecular mass BP180 complex that is observed when unheated sodium dodecyl sulfate extracts of human skin or keratinocytes are subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. In heated extracts BP180 is present as a monomer

  3. Metal–organic frameworks constructed from monomeric, dimeric and trimeric phenanthroline citrate zinc building units

    OpenAIRE

    Zhang, Rong-Hua; Xia, Wen-Sheng; Wang, Hong-Xin; Zhou, Zhao-Hui

    2009-01-01

    Adduct of mononuclear and dinuclear citrate zinc complex [Zn(Hcit)(phen)(H2O)][Zn2(Hcit)(phen)2(H2O)3]·13.5H2O (1) and its aggregate [Zn3(Hcit)2(phen)4]n·14nH2O (2) (H4cit = citric acid, phen = 1,10-phenanthroline) were synthesized in weak acidic solutions. The former was obtained from the reaction of zinc nitrate, citric acid and phenanthroline in a molar ratio of 3 : 2 : 3, while a slightly excess of phenanthroline results in the formation of the polymeric product 2 in a molar ratio of 3 : ...

  4. Theoretical research program to study transition metal trimers and embedded clusters

    Science.gov (United States)

    Walch, Stephen P.

    1987-01-01

    The results of ab-initio calculations are reported for (1) small transition metal clusters and (2) potential energy surfaces for chemical reactions important in hydrogen combustion and high temperature air chemistry.

  5. Atom-dimer scattering and long-lived trimers in fermionic mixtures

    NARCIS (Netherlands)

    J. Levinsen; T.G. Tiecke; J.T.M. Walraven; D.S. Petrov

    2009-01-01

    We consider a heteronuclear fermionic mixture on the molecular side of an interspecies Feshbach resonance and discuss atom-dimer scattering properties in uniform space and in the presence of an external confining potential, restricting the system to a quasi-two-dimensional geometry. We find that the

  6. Synthesis and physical properties of new coco-oleic dimer and trimer plus estolide branched esters

    Science.gov (United States)

    Estolides are a class of esters based on vegetable oils that are formed when the carboxylic acid functionality of one fatty acid reacts at the site of unsaturation of another fatty acid to form an ester linkage. The objective of this preliminary study was to separate coco-oleic estolide into two com...

  7. Fluid shear stress sensitizes cancer cells to receptor-mediated apoptosis via trimeric death receptors

    International Nuclear Information System (INIS)

    Cancer metastasis, the process of cancer cell migration from a primary to distal location, typically leads to a poor patient prognosis. Hematogenous metastasis is initiated by intravasation of circulating tumor cells (CTCs) into the bloodstream, which are then believed to adhere to the luminal surface of the endothelium and extravasate into distal locations. Apoptotic agents such as tumor necrosis factor apoptosis-inducing ligand (TRAIL), whether in soluble ligand form or expressed on the surface of natural killer cells, have shown promise in treating CTCs to reduce the probability of metastasis. The role of hemodynamic shear forces in altering the cancer cell response to apoptotic agents has not been previously investigated. Here, we report that human colon cancer COLO 205 and prostate cancer PC-3 cells exposed to a uniform fluid shear stress in a cone-and-plate viscometer become sensitized to TRAIL-induced apoptosis. Shear-induced sensitization directly correlates with the application of fluid shear stress, and TRAIL-induced apoptosis increases in a fluid shear stress force- and time-dependent manner. In contrast, TRAIL-induced necrosis is not affected by the application fluid shear stress. Interestingly, fluid shear stress does not sensitize cancer cells to apoptosis when treated with doxorubicin, which also induces apoptosis in cancer cells. Caspase inhibition experiments reveal that shear stress-induced sensitization to TRAIL occurs via caspase-dependent apoptosis. These results suggest that physiological fluid shear forces can modulate receptor-mediated apoptosis of cancer cells in the presence of apoptotic agents. (paper)

  8. Fluorous imidazolium room-temperature ionic liquids based on HFPO trimer

    Czech Academy of Sciences Publication Activity Database

    Kysilka, O.; Rybáčková, M.; Skalický, M.; Kvíčalová, Magdalena; Cvačka, Josef; Kvíčala, J.

    2009-01-01

    Roč. 130, č. 7 (2009), s. 629-639. ISSN 0022-1139 R&D Projects: GA MŠk(CZ) LC06070 Institutional research plan: CEZ:AV0Z40320502; CEZ:AV0Z40550506 Keywords : ionic liquid * fluorous * RTIL Subject RIV: CC - Organic Chemistry Impact factor: 1.730, year: 2009

  9. Structure of a Filament-Like Actin Trimer Bound to the Bacterial Effector VopL

    OpenAIRE

    Zahm, Jacob A.; Padrick, Shae B.; Chen, Zhucheng; Pak, Chi W.; Yunus, Ali A.; Henry, Lisa; Tomchick, Diana R.; Chen, Zhe; Rosen, Michael K.

    2013-01-01

    Bacterial pathogens use secreted effector proteins to subvert host-cell defenses. VopL is an effector protein from Vibrio parahaemolyticus that nucleates actin filaments. VopL consists of a VopL C-terminal Domain (VCD) and a tandem array of three WASP homology 2 (WH2) motifs. Here we report the crystal structure of the VCD dimer bound to actin. The VCD binds three actin monomers in a spatial arrangement close to that in the canonical actin filament. In this configuration each actin can readil...

  10. DCP1 forms asymmetric trimers to assemble into active mRNA decapping complexes in metazoa

    OpenAIRE

    Tritschler, Felix; Braun, Joerg E.; Motz, Carina; Igreja, Catia; Haas, Gabrielle; Truffault, Vincent; Izaurralde, Elisa; Weichenrieder, Oliver

    2009-01-01

    DCP1 stimulates the decapping enzyme DCP2, which removes the mRNA 5′ cap structure committing mRNAs to degradation. In multicellular eukaryotes, DCP1-DCP2 interaction is stabilized by additional proteins, including EDC4. However, most information on DCP2 activation stems from studies in S. cerevisiae, which lacks EDC4. Furthermore, DCP1 orthologs from multicellular eukaryotes have a C-terminal extension, absent in fungi. Here, we show that in metazoa, a conserved DCP1 C-terminal domain drives...

  11. MicroProtein-mediated recruitment of CONSTANS into a TOPLESS trimeric complex represses flowering in Arabidopsis

    DEFF Research Database (Denmark)

    Graeff, Moritz; Straub, Daniel; Eguen, Tenai E.;

    2016-01-01

    Arabidopsis thaliana microProteins, miP1a and miP1b, physically interact with CONSTANS (CO) a potent regulator of flowering time. The miP1a/b-type microProteins evolved in dicotyledonous plants and have an additional carboxy-terminal PF(V/L)FL motif. This motif enables miP1a/b microProteins to interact with...... TOPLESS/TOPLESS-RELATED (TPL/TPR) proteins. Interaction of CO with miP1a/b/TPL causes late flowering due to a failure in the induction of FLOWERING LOCUS T (FT) expression under inductive long day conditions. Both miP1a and miP1b are expressed in vascular tissue, where CO and FT are active. Genetically......MicroProteins are short, single domain proteins that act by sequestering larger, multi-domain proteins into non-functional complexes. MicroProteins have been identified in plants and animals, where they are mostly involved in the regulation of developmental processes. Here we show that two...

  12. Antibody to gp41 MPER alters functional properties of HIV-1 Env without complete neutralization.

    Directory of Open Access Journals (Sweden)

    Arthur S Kim

    2014-07-01

    Full Text Available Human antibody 10E8 targets the conserved membrane proximal external region (MPER of envelope glycoprotein (Env subunit gp41 and neutralizes HIV-1 with exceptional potency. Remarkably, HIV-1 containing mutations that reportedly knockout 10E8 binding to linear MPER peptides are partially neutralized by 10E8, producing a local plateau in the dose response curve. Here, we found that virus partially neutralized by 10E8 becomes significantly less neutralization sensitive to various MPER antibodies and to soluble CD4 while becoming significantly more sensitive to antibodies and fusion inhibitors against the heptad repeats of gp41. Thus, 10E8 modulates sensitivity of Env to ligands both pre- and post-receptor engagement without complete neutralization. Partial neutralization by 10E8 was influenced at least in part by perturbing Env glycosylation. With unliganded Env, 10E8 bound with lower apparent affinity and lower subunit occupancy to MPER mutant compared to wild type trimers. However, 10E8 decreased functional stability of wild type Env while it had an opposite, stabilizing effect on MPER mutant Envs. Clade C isolates with natural MPER polymorphisms also showed partial neutralization by 10E8 with altered sensitivity to various gp41-targeted ligands. Our findings suggest a novel mechanism of virus neutralization by demonstrating how antibody binding to the base of a trimeric spike cross talks with adjacent subunits to modulate Env structure and function. The ability of an antibody to stabilize, destabilize, partially neutralize as well as alter neutralization sensitivity of a virion spike pre- and post-receptor engagement may have implications for immunotherapy and vaccine design.

  13. Mucosal B Cells Are Associated with Delayed SIV Acquisition in Vaccinated Female but Not Male Rhesus Macaques Following SIVmac251 Rectal Challenge.

    Directory of Open Access Journals (Sweden)

    Iskra Tuero

    2015-08-01

    Full Text Available Many viral infections, including HIV, exhibit sex-based pathogenic differences. However, few studies have examined vaccine-related sex differences. We compared immunogenicity and protective efficacy of monomeric SIV gp120 with oligomeric SIV gp140 in a pre-clinical rhesus macaque study and explored a subsequent sex bias in vaccine outcome. Each immunization group (16 females, 8 males was primed twice mucosally with replication-competent Ad-recombinants encoding SIVsmH4env/rev, SIV239gag and SIV239nefΔ1-13 and boosted twice intramuscularly with SIVmac239 monomeric gp120 or oligomeric gp140 in MF59 adjuvant. Controls (7 females, 5 males received empty Ad and MF59. Up to 9 weekly intrarectal challenges with low-dose SIVmac251 were administered until macaques became infected. We assessed vaccine-induced binding, neutralizing, and non-neutralizing antibodies, Env-specific memory B cells and plasmablasts/plasma cells (PB/PC in bone marrow and rectal tissue, mucosal Env-specific antibodies, and Env-specific T-cells. Post-challenge, only one macaque (gp140-immunized remained uninfected. However, SIV acquisition was significantly delayed in vaccinated females but not males, correlated with Env-specific IgA in rectal secretions, rectal Env-specific memory B cells, and PC in rectal tissue. These results extend previous correlations of mucosal antibodies and memory B cells with protective efficacy. The gp140 regimen was more immunogenic, stimulating elevated gp140 and cyclic V2 binding antibodies, ADCC and ADCP activities, bone marrow Env-specific PB/PC, and rectal gp140-specific IgG. However, immunization with gp120, the form of envelope immunogen used in RV144, the only vaccine trial to show some efficacy, provided more significant acquisition delay. Further over 40 weeks of follow-up, no gp120 immunized macaques met euthanasia criteria in contrast to 7 gp140-immunized and 2 control animals. Although males had higher binding antibodies than females, ADCC

  14. The three isoforms of the light-harvesting complex II Spectroscopic features, trimer formation, and functional roles

    CERN Document Server

    Standfuss, Jorg

    2004-01-01

    The major light-harvesting complex (LHC-II) of higher plants plays a crucial role in capturing light energy for photosynthesis and in regulating the flow of energy within the photosynthetic apparatus. Native LHC-II isolated from plant tissue consists of three isoforms, Lhcb1, Lhcb2, and Lhcb3, which form homo- and heterotrimers. All three isoforms are highly conserved among different species, suggesting distinct functional roles. We produced the three LHC-II isoforms by heterologous expression of the polypeptide in Escherichia coli and in vitro refolding with purified pigments. Although Lhcb1 and Lhcb2 are very similar in polypeptide sequence and pigment content, Lhcb3 is clearly different because it lacks an N-terminal phosphorylation site and has a higher chlorophyll a/b ratio, suggesting the absence of one chlorophyll b. Low temperature absorption and fluorescence emission spectra of the pure isoforms revealed small but significant differences in pigment organization. The oligomeric state of the pure isofo...

  15. Characterization of trimeric Photosystem I particles from the prochlorophyte Prochlorothrix hollandica by electron microscopy and image analysis

    NARCIS (Netherlands)

    Staay, Georg W.M. van der; Boekema, Egbert J.; Dekker, Jan P.; Matthijs, Hans C.P.

    1993-01-01

    Photosystem I particles from Prochlorothrix hollandica were isolated from dodecylmaltoside solubilized thylakoid membranes on sucrose gradients in the presence of dodecylmaltoside. The particles were characterized by electron microscopy and image reconstruction techniques. The lowest, major green ba

  16. Daple is a novel non-receptor GEF required for trimeric G protein activation in Wnt signaling.

    Science.gov (United States)

    Aznar, Nicolas; Midde, Krishna K; Dunkel, Ying; Lopez-Sanchez, Inmaculada; Pavlova, Yelena; Marivin, Arthur; Barbazán, Jorge; Murray, Fiona; Nitsche, Ulrich; Janssen, Klaus-Peter; Willert, Karl; Goel, Ajay; Abal, Miguel; Garcia-Marcos, Mikel; Ghosh, Pradipta

    2015-01-01

    Wnt signaling is essential for tissue homeostasis and its dysregulation causes cancer. Wnt ligands trigger signaling by activating Frizzled receptors (FZDRs), which belong to the G-protein coupled receptor superfamily. However, the mechanisms of G protein activation in Wnt signaling remain controversial. In this study, we demonstrate that FZDRs activate G proteins and trigger non-canonical Wnt signaling via the Dishevelled-binding protein, Daple. Daple contains a Gα-binding and activating (GBA) motif, which activates Gαi proteins and an adjacent domain that directly binds FZDRs, thereby linking Wnt stimulation to G protein activation. This triggers non-canonical Wnt responses, that is, suppresses the β-catenin/TCF/LEF pathway and tumorigenesis, but enhances PI3K-Akt and Rac1 signals and tumor cell invasiveness. In colorectal cancers, Daple is suppressed during adenoma-to-carcinoma transformation and expressed later in metastasized tumor cells. Thus, Daple activates Gαi and enhances non-canonical Wnt signaling by FZDRs, and its dysregulation can impact both tumor initiation and progression to metastasis. PMID:26126266

  17. A recombinant rabies vaccine expressing the trimeric form of the glycoprotein confers enhanced immunogenicity and protection in outbred mice.

    NARCIS (Netherlands)

    Koraka, Penelope; Bosch, Berend-Jan; Cox, Manon; Chubet, Rick; Amerongen, Geert van; Lövgren-Bengtsson, Karen; Martina, Byron E E; Roose, Jouke; Rottier, Peter J M; Osterhaus, Albert D M E

    2014-01-01

    Rabies is a disease characterized by an invariably lethal encephalitis of viral origin that can be controlled by preventive vaccination programs of wildlife, domestic animals and humans in areas with a high risk of exposure. Currently available vaccines are expensive, cumbersome to produce and requi

  18. The host-binding domain of the P2 phage tail spike reveals a trimeric iron-binding structure

    International Nuclear Information System (INIS)

    The C-terminal domain of a bacteriophage P2 tail-spike protein, gpV, was crystallized and its structure was solved at 1.27 Å resolution. The refined model showed a triple β-helix structure and the presence of iron, calcium and chloride ions. The adsorption and infection of bacteriophage P2 is mediated by tail fibres and tail spikes. The tail spikes on the tail baseplate are used to irreversibly adsorb to the host cells. Recently, a P2 phage tail-spike protein, gpV, was purified and it was shown that a C-terminal domain, Ser87–Leu211, is sufficient for the binding of gpV to host Escherichia coli membranes [Kageyama et al. (2009 ▶), Biochemistry, 48, 10129–10135]. In this paper, the crystal structure of the C-terminal domain of P2 gpV is reported. The structure is a triangular pyramid and looks like a spearhead composed of an intertwined β-sheet, a triple β-helix and a metal-binding region containing iron, calcium and chloride ions

  19. Towards the mechanism of trimeric purine nucleoside phosphorylases: Stopped-flow studies of binding of multisubstrate analogue inhibitor - 2-amino-9-[2-(phosphonomethoxy)ethyl]-6-sulfanylpurine

    Czech Academy of Sciences Publication Activity Database

    Wielgus-Kutrowska, B.; Antosiewicz, J. M.; Dlugosz, M.; Holý, Antonín; Bzowska, A.

    2007-01-01

    Roč. 125, 2/3 (2007), s. 260-268. ISSN 0301-4622 R&D Projects: GA AV ČR IBS4055109 Grant ostatní: Descartes Prize(XE) HPAW-CT-2002-9001 Institutional research plan: CEZ:AV0Z40550506 Keywords : PNP * PME-6-thio-Gua * fluorescence * stopped-flow Subject RIV: CC - Organic Chemistry Impact factor: 1.913, year: 2007

  20. Theoretical study of weakly bound vibrational states of the sodium trimer. Numerical methods; prospects for the formation of Na3 in an ultracold gas

    International Nuclear Information System (INIS)

    A Mapped Fourier Grid method for solving the radial Schroedinger equation is improved. It is observed that a discrete sine and cosine transform algorithm allows to compute a Hamiltonian matrix the spectrum of which is free of spurious eigenvalues. - The energies of the highest, least bound vibrational states of the Na - Na2 van der Waals complex are computed using a hyperspherical diabatic-by-sector method. The computed levels are analyzed using quantum defect theory. (orig.)

  1. Direct observation of high-spin states in manganese dimer and trimer cations by x-ray magnetic circular dichroism spectroscopy in an ion trap

    Energy Technology Data Exchange (ETDEWEB)

    Zamudio-Bayer, V. [Physikalisches Institut, Universität Freiburg, Stefan-Meier-Straße 21, 79104 Freiburg (Germany); Institut für Methoden und Instrumentierung der Forschung mit Synchrotronstrahlung, Helmholtz-Zentrum Berlin für Materialien und Energie GmbH, Albert-Einstein-Straße 15, 12489 Berlin (Germany); Hirsch, K.; Langenberg, A.; Kossick, M. [Institut für Methoden und Instrumentierung der Forschung mit Synchrotronstrahlung, Helmholtz-Zentrum Berlin für Materialien und Energie GmbH, Albert-Einstein-Straße 15, 12489 Berlin (Germany); Institut für Optik und Atomare Physik, Technische Universität Berlin, Hardenbergstraße 36, 10623 Berlin (Germany); Ławicki, A.; Lau, J. T., E-mail: tobias.lau@helmholtz-berlin.de [Institut für Methoden und Instrumentierung der Forschung mit Synchrotronstrahlung, Helmholtz-Zentrum Berlin für Materialien und Energie GmbH, Albert-Einstein-Straße 15, 12489 Berlin (Germany); Terasaki, A. [Cluster Research Laboratory, Toyota Technological Institute, 717-86 Futamata, Ichikawa, Chiba 272-0001 (Japan); Department of Chemistry, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Issendorff, B. von [Physikalisches Institut, Universität Freiburg, Stefan-Meier-Straße 21, 79104 Freiburg (Germany)

    2015-06-21

    The electronic structure and magnetic moments of free Mn{sub 2}{sup +} and Mn{sub 3}{sup +} are characterized by 2p x-ray absorption and x-ray magnetic circular dichroism spectroscopy in a cryogenic ion trap that is coupled to a synchrotron radiation beamline. Our results directly show that localized magnetic moments of 5 μ{sub B} are created by 3d{sup 5}({sup 6}S) states at each ionic core, which are coupled ferromagnetically to form molecular high-spin states via indirect exchange that is mediated in both cases by a delocalized valence electron in a singly occupied 4s derived antibonding molecular orbital with an unpaired spin. This leads to total magnetic moments of 11 μ{sub B} for Mn{sub 2}{sup +} and 16 μ{sub B} for Mn{sub 3}{sup +}, with no contribution of orbital angular momentum.

  2. Direct observation of high-spin states in manganese dimer and trimer cations by x-ray magnetic circular dichroism spectroscopy in an ion trap

    International Nuclear Information System (INIS)

    The electronic structure and magnetic moments of free Mn2+ and Mn3+ are characterized by 2p x-ray absorption and x-ray magnetic circular dichroism spectroscopy in a cryogenic ion trap that is coupled to a synchrotron radiation beamline. Our results directly show that localized magnetic moments of 5 μB are created by 3d5(6S) states at each ionic core, which are coupled ferromagnetically to form molecular high-spin states via indirect exchange that is mediated in both cases by a delocalized valence electron in a singly occupied 4s derived antibonding molecular orbital with an unpaired spin. This leads to total magnetic moments of 11 μB for Mn2+ and 16 μB for Mn3+, with no contribution of orbital angular momentum

  3. The crystal structure of the calcium-bound con-G[Q6A] peptide reveals a novel metal-dependent helical trimer

    OpenAIRE

    Cnudde, Sara E.; Prorok, Mary; Jia, Xaofei; Castellino, Francis J.; Geiger, James H.

    2010-01-01

    The ability to form and control both secondary structure and oligomerization in short peptides has proven to be challenging due to the structural instability of such peptides. The conantokin peptides are a family of gamma-carboxy-glutamic acid containing peptides produced in the venoms of predatory sea snails of the conus family. They are examples of short peptides that form stable helical structures, especially in the presence of divalent cations. Both monomeric and dimeric conantokin peptid...

  4. Symmetrical trimeric star-shaped mesogens based on 1,3,5-trisubstituted benzene incorporating Schiff base and azobenzene fragments as the peripheral units: Synthesis and mesomorphic properties

    Indian Academy of Sciences (India)

    Guan-Yeow Yeap; Yew-Hong Ooi; Nozomi Uchida; Masato M Ito

    2014-05-01

    Two series of symmetrical three-armed star-shaped mesogens based on 1,3,5-trihydroxybenzene as a core unit, interconnecting three Schiff base or azobenzene moieties via oxymethylene spacers have been synthesized and characterized by spectroscopic techniques. Every member in these series possesses either chlorine (Cl) or bromine (Br) terminal atom, with different alkyl spacer length (CH2 whereby ranging from 3 to 6). Their thermal stability and mesomorphic properties are investigated by employing DSC and POM. The dependence of phase transition in relation to the alkyl spacer length is shown by both series. These star-shaped mesogens exhibit only nematic and smectic phases. The difference between the two series lies on the structure of linking group in the peripheral units (-CH=N- for series PSB-X- and -N=N- for series PAZ-X-). Therefore, a comparison study of the mesomorphic properties between these two series of star-shaped mesogens is discussed whereby the azobenzene-basedmesogens are thermally more stable than the Schiff base counterpart. In addition, soft crystalline phase is observed for the azobenzene-based star-shaped mesogens possessing hexyl alkyl spacer.

  5. Direct Observation of High-Spin States in Manganese Dimer and Trimer Cations by X-ray Magnetic Circular Dichroism Spectroscopy in an Ion Trap

    CERN Document Server

    Zamudio-Bayer, Vicente; Langenberg, Andreas; Kossick, Martin; Ławicki, Arkadiusz; Terasaki, Akira; von Issendorff, Bernd; Lau, J Tobias

    2015-01-01

    The electronic structure and magnetic moments of free Mn$_2^+$ and Mn$_3^+$ are characterized by $2p$ x-ray absorption and x-ray magnetic circular dichroism spectroscopy in a cryogenic ion trap that is coupled to a synchrotron radiation beamline. Our results show directly that localized magnetic moments of 5 $\\mu_B$ are created by $3d^5 (^6\\mathrm{S})$ states at each ionic core, which are coupled in parallel to form molecular high-spin states via indirect exchange that is mediated in both cases by a delocalized valence electron in a singly-occupied $4s$ derived orbital with an unpaired spin. This leads to total magnetic moments of 11 $\\mu_B$ for Mn$_2^+$ and 16 $\\mu_B$ for Mn$_3^+$, with no contribution of orbital angular momentum.

  6. Benchmark RI-MP2 database of nucleic acid base trimers: performance of different density functional models for prediction of structures and binding energies

    Czech Academy of Sciences Publication Activity Database

    Kabeláč, Martin; Valdes, Haydee; Sherer, E. C.; Cramer, Ch. J.; Hobza, Pavel

    2007-01-01

    Roč. 9, č. 36 (2007), s. 5000-5008. ISSN 1463-9076 R&D Projects: GA MŠk LC512; GA ČR GA203/05/0009 Grant ostatní: NSF(US) CHE-0615401 Institutional research plan: CEZ:AV0Z40550506 Keywords : IR spectrum * guanine * deoxyguanosine Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.343, year: 2007

  7. The effect of detergents on trimeric G-protein activity in isolated plasma membranes from rat brain cortex: Correlation with studies of DPH and Laurdan fluorescence

    Czech Academy of Sciences Publication Activity Database

    Sýkora, Jan; Bouřová, Lenka; Hof, Martin; Svoboda, Petr

    2009-01-01

    Roč. 1788, č. 2 (2009), s. 324-332. ISSN 0005-2736 R&D Projects: GA MŠk(CZ) LC06063; GA MŠk(CZ) LC554; GA ČR(CZ) GA309/06/0121; GA AV ČR(CZ) IAA500110606 Institutional research plan: CEZ:AV0Z40400503; CEZ:AV0Z50110509 Keywords : detergent * fluorescence * stready-state * time-resolved Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.998, year: 2009

  8. Alkyne Hydroamination and Trimerization with Titanium Bis(phenolate)pyridine Complexes: Evidence for Low-Valent Titanium Intermediates and Synthesis of an Ethylene Adduct of Titanium(II)

    KAUST Repository

    Tonks, Ian A.

    2013-06-24

    A class of titanium precatalysts of the type (ONO)TiX2 (ONO = pyridine-2,6-bis(4,6-di-tert-butylphenolate); X = Bn, NMe2) has been synthesized and crystallographically characterized. The (ONO)TiX2 (X = Bn, NMe2, X2 = NPh) complexes are highly active precatalysts for the hydroamination of internal alkynes with primary arylamines and some alkylamines. A class of titanium imido/ligand adducts, (ONO)Ti(L)(NR) (L = HNMe2, py; R = Ph, tBu), have also been synthesized and characterized and provide structural analogues to intermediates on the purported catalytic cycle. Furthermore, these complexes exhibit unusual redox behavior. (ONO)TiBn2 (1) promotes the cyclotrimerization of electron-rich alkynes, likely via a catalytically active TiII species that is generated in situ from 1. Depending on reaction conditions, these TiII species are proposed to be generated through Ti benzylidene or imido intermediates. A formally TiII complex, (ONO)Ti II(η2-C2H4)(HNMe2) (7), has been prepared and structurally characterized. © 2013 American Chemical Society.

  9. Identification of an additional class of C3-binding membrane proteins of human peripheral blood leukocytes and cell lines.

    OpenAIRE

    Cole, J L; Housley, G A; Dykman, T R; MacDermott, R P; Atkinson, J P

    1985-01-01

    Proteins binding the third component of complement (C3) were isolated by affinity chromatography from surface-labeled solubilized membranes of human peripheral blood cells and cell lines. The isolated molecules were subjected to NaDodSO4/PAGE, and autoradiographs of these gels indicated that C3-binding proteins could be divided into three groups based on Mr: (i) gp200, an approximately 200,000 Mr molecule previously identified as the C3b/C4b receptor or CR1; (ii) gp140, an approximately 140,0...

  10. Dense display of HIV-1 envelope spikes on the lambda phage scaffold does not result in the generation of improved antibody responses to HIV-1 Env

    OpenAIRE

    Mattiacio, Jonelle; Walter, Scott; Brewer, Matt; Domm, William; Friedman, Alan E.; Dewhurst, Stephen

    2011-01-01

    The generation of strong, virus-neutralizing antibody responses to the HIV-1 envelope spike (Env) is a major goal in HIV-1 vaccine research. To try to enhance the Env-specific response, we displayed oligomeric gp140 on a virus-like scaffold provided by the lambda phage capsid. To do this, an in vitro complementation system was used to “decorate” phage particles with glycosylated, mammalian cell-derived envelope oligomers. We compared the immune response to lambda phage particles displaying HI...

  11. Effect of Preexisting Immunity to Adenovirus Human Serotype 5 Antigens on the Immune Responses of Nonhuman Primates to Vaccine Regimens Based on Human- or Chimpanzee-Derived Adenovirus Vectors▿

    OpenAIRE

    McCoy, Kimberly; Tatsis, Nia; Korioth-Schmitz, Birgit; Lasaro, Marcio O; Scott E Hensley; Lin, Shih-Wen; Li, Yan; Giles-Davis, Wynetta; Cun, Ann; Zhou, Dongming; Xiang, Zhiquan; Letvin, Norman L.; Hildegund C J Ertl

    2007-01-01

    In this study we compared a prime-boost regimen with two serologically distinct replication-defective adenovirus (Ad) vectors derived from chimpanzee serotypes C68 and C1 expressing Gag, Pol, gp140, and Nef of human immunodeficiency virus type 1 with a regimen in which replication-defective Ad vectors of the human serotype 5 (AdHu5) were given twice. Experiments were conducted in rhesus macaques that had or had not been preexposed to antigens of AdHu5. There was no significant difference in T...

  12. Complexes of platinum(II) containing neutral and deprotonated 9-methyladenine. Synthesis, x-ray structures, and NMR studies on the cyclic trimer cis-[L2Pt[9-MeAd([bond]H)

    Science.gov (United States)

    Longato, Bruno; Pasquato, Lucia; Mucci, Adele; Schenetti, Luisa; Zangrando, Ennio

    2003-12-01

    The dinuclear hydroxo complex cis-[L(2)Pt(mu-OH)](2)(NO(3))(2) (L = PMePh(2), 1), in CH(2)Cl(2), CH(3)CN, or DMF solution, deprotonates the NH(2) group of 9-methyladenine (9-MeAd) to give the complex cis-[L(2)Pt[9-MeAd(-H)

  13. Beyond the Dimer and Trimer: Tetraspiro[2.1.2(5) .1.2(9) .1.2(13) .1(3) ] hexadecane-1,3,5,7-tetraone-the Cyclic Tetramer of Carbonylcyclopropane.

    Science.gov (United States)

    Sedenkova, Kseniya N; Averina, Elena B; Grishin, Yuri K; Andriasov, Kristian S; Stepanova, Svetlana A; Roznyatovsky, Vitaly A; Kutateladze, Andrei G; Rybakov, Victor B; Albov, Dmitry V; Kuznetsova, Tamara S; Zefirov, Nikolay S

    2016-03-14

    Tetraspiro[2.1.2(5) .1.2(9) .1.2(13) .1(3) ]hexadecane-1,3,5,7-tetraone 4, a unique tetraketone containing a cyclooctane core and four spiroannelated cyclopropane moieties, represents the previously unknown cyclotetramer of carbonylcyclopropane. For this purpose oxidation of the parent polyspirocyclic hydrocarbon was examined under various oxidative conditions, and the reactivity of oxidants towards methylene groups of the eight-membered cycle, activated by adjacent spirocyclopropane rings, was evaluated and contrasted. Whereas the treatment of tetraspirohexadecane with ozone resulted in monooxidation, its reaction with methyl(trifluoromethyl)dioxirane afforded the product of four-fold oxidation, triketoalcohol 10. Subsequent oxidation of the latter with Dess-Martin periodinane gave the target tetraketone 4. PMID:26762227

  14. [(≢SiO)TaVCl2Me2]: A well-defined silica-supported tantalum(V) surface complex as catalyst precursor for the selective cocatalyst-free trimerization of ethylene

    KAUST Repository

    Chen, Yin

    2012-10-22

    On the surface of it: In the absence of co-catalyst, a well-defined silica-supported surface organometallic complex [(≢SiO)Ta VCl2Me2] selectively catalyzes the oligomerization of ethylene. The use of surface organometallic species allows three different pathways to be determined for the reduction of TaV to TaIII species under pressure of ethylene. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Plasma Membrane Density of GABA(B)-R1a, GABA(B)-R1b, GABA-R2 and Trimeric G-proteins in the Course of Postnatal Development of Rat Brain Cortex

    Czech Academy of Sciences Publication Activity Database

    Dlouhá, Kateřina; Kagan, Dmytro; Roubalová, Lenka; Ujčíková, Hana; Svoboda, Petr

    2013-01-01

    Roč. 62, č. 5 (2013), s. 547-559. ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP207/12/0919; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : GABAB-receptors * postnatal development * rat brain cortex * G-proteins * Na, K-ATPase Subject RIV: CE - Biochemistry Impact factor: 1.487, year: 2013

  16. Long-Term Acclimation of the Cyanobacterium Synechocystis sp PCC 6803 to High Light Is Accompanied by an Enhanced Production of Chlorophyll That Is Preferentially Channeled to Trimeric Photosystem I

    Czech Academy of Sciences Publication Activity Database

    Kopečná, Jana; Komenda, Josef; Bučinská, Lenka; Sobotka, Roman

    2012-01-01

    Roč. 160, č. 4 (2012), s. 2239-2250. ISSN 0032-0889 R&D Projects: GA MŠk(CZ) ED2.1.00/03.0110; GA ČR GAP501/10/1000; GA ČR GBP501/12/G055 Institutional support: RVO:61388971 Keywords : CAB-LIKE-PROTEINS * SP PCC-6803 * PHOTOSYNTHETIC APPARATUS Subject RIV: EE - Microbiology, Virology Impact factor: 6.555, year: 2012

  17. 表达猪H1N1亚型流感病毒三聚体HA的重组慢病毒包装%Packaging of recombinant lentivirus expressing trimeric HA of swine HIN1 influenza virus

    Institute of Scientific and Technical Information of China (English)

    李鑫; 宋战昀; 朱利塞; 樊娇; 王广美; 丛彦龙; 丁壮

    2012-01-01

    To package a recombinant lentivirus which can express HA-GCN4p Ⅱ fusion protein. The HA gene derived from swine H1N1 influenza virus was amplified by RT-PCR and linked to GCN4p Ⅱ by a GS-linker. The expression of HA GCN4p Ⅱand packaging of recombinant lentivirus were identified by the results of green fluorescence,transduction efficiency, SDS-PAGE, and Western blot. A recombinant lentivirus LV-HA-GCN4p Ⅱ was achieved with a titer of 1.1 × 10^6 TU/mL,which can be transduced in 293T ceils efficiently. The achievement of a recombinant lentivirus is not only beneficial to further prepare a swine H1N1 influenza vaccine,but also helpful to pave the way for constructing a pseudotyped lentiviral system stably expressing HA-GCN4p Ⅱ.%以RT—PCR扩增猪H1N1流感病毒HA基因,用GS-linker使HA与GCN4pⅡ连接。构建慢病毒蛋白表达系统。通过观察荧光、病毒转导效率、SDS—PAGE、Western blot验证重组慢病毒包装和HA—GCN4pⅡ融合蛋白表达情况。该系统能使外源基因得到持久和稳定的表达。结果,包装获得能够融合表达HA-GCN4pⅡ的重组慢病毒LV—HA-GCN4pⅡ,病毒滴度为1.1×10^6TU/mL;LV—HA—GCN4pⅡ能有效转导293T细胞。本试验成功构建了表达HA—GCN4PⅡ融合蛋白的慢病毒表达载体,获得的重组慢病毒不仅为后续动物试验测定其诱导的体液免疫和细胞免疫水平奠定了基础,同时也为研制猪H1N1亚型流感疫苗做出了有益尝试。

  18. Single-ion anisotropy and exchange interactions in the cyano-bridged trimers MnIII2MIII(CN)6 (MIII = Co, Cr, Fe) species incorporating [Mn(5-Brsalen)]+ units: an inelastic neutron scattering and magnetic susceptibility study

    DEFF Research Database (Denmark)

    Tregenna-Piggott, Philip L W; Sheptyakov, Denis; Keller, Lukas;

    2009-01-01

    The electronic structures of the compounds K[(5-Brsalen)(2)(H(2)O)(2)-Mn(2)M(III)(CN)(6)].2H(2)O (M(III) = Co(III), Cr(III), Fe(III)) have been determined by inelastic neutron scattering (INS) and magnetic susceptibility studies, revealing the manganese(III) single-ion anisotropy and exchange int...

  19. The wing in yeast heat shock transcription factor (HSF) DNA-binding domain is required for full activity

    OpenAIRE

    Cicero, Marco P.; T. Hubl, Susan; Harrison, Celia J.; Littlefield, Otis; Hardy, Jeanne A.; Nelson, Hillary C. M.

    2001-01-01

    The yeast heat shock transcription factor (HSF) belongs to the winged helix family of proteins. HSF binds DNA as a trimer, and additional trimers can bind DNA co-operatively. Unlike other winged helix–turn–helix proteins, HSF’s wing does not appear to contact DNA, as based on a previously solved crystal structure. Instead, the structure implies that the wing is involved in protein–protein interactions, possibly within a trimer or between adjacent trimers. To unders...

  20. HIV-1 clade promoters strongly influence spatial and temporal dynamics of viral replication in vivo

    Science.gov (United States)

    Centlivre, Mireille; Sommer, Peter; Michel, Marie; Fang, Raphaël Ho Tsong; Gofflo, Sandrine; Valladeau, Jenny; Schmitt, Nathalie; Thierry, Françoise; Hurtrel, Bruno; Wain-Hobson, Simon; Sala, Monica

    2005-01-01

    Although the primary determinant of cell tropism is the interaction of viral envelope or capsid proteins with cellular receptors, other viral elements can strongly modulate viral replication. While the HIV-1 promoter is polymorphic for a variety of transcription factor binding sites, the impact of these polymorphisms on viral replication in vivo is not known. To address this issue, we engineered isogenic SIVmac239 chimeras harboring the core promoter/enhancer from HIV-1 clades B, C, and E. Here it is shown that the clade C and E core promoters/enhancers bear a noncanonical activator protein–1 (AP-1) binding site, absent from the corresponding clade B region. Relative ex vivo replication of chimeras was strongly dependent on the tissue culture system used. Notably, in thymic histocultures, replication of the clade C chimera was favored by IL-7 enrichment, which suggests that the clade C polymorphism in the AP-1 and NF-κB binding sites is involved. Simultaneous infection of rhesus macaques with the 3 chimeras revealed a strong predominance of the clade C chimera during primary infection. Thereafter, the B chimera dominated in all tissues. These data show that the clade C promoter is particularly adapted to sustain viral replication in primary viremia and that clade-specific promoter polymorphisms constitute a major determinant for viral replication. PMID:15690084

  1. Comparación de la antigenicidad de un peptido sintetico y una proteína recombinante de la región de transmembrana (gp 36) del VIH-2

    OpenAIRE

    Milenen Hernández Marin; Lilliam Pozo Peña; Martha Amat Arenas; Chryslaine Rodríguez Tanty; David Higginson Clarke

    2009-01-01

    El virus de la inmunodeficiencia humana del tipo 2 (VIH-2) se detectó en países de África Occidental y es otro agente causal del Síndrome de Inmunodeficiencia Adquirida (SIDA). El gen env codifica la síntesis de la proteína precursora, gp140, que es procesada por una proteasa del virus en dos proteínas: gp36 y gp105. Los péptidos sintéticos y proteínas recombinantes de la glicoproteína de la transmembrana gp36 muestran una elevada reactividad y especificidad en la detección de anticuerpos en ...

  2. Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site

    Directory of Open Access Journals (Sweden)

    Todd Bradley

    2016-01-01

    Full Text Available Antibodies that neutralize autologous transmitted/founder (TF HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs against neutralization-resistant (Tier-2 viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization.

  3. Codelivery of Envelope Protein in Alum with MVA Vaccine Induces CXCR3-Biased CXCR5+ and CXCR5- CD4 T Cell Responses in Rhesus Macaques.

    Science.gov (United States)

    Iyer, Smita S; Gangadhara, Sailaja; Victor, Blandine; Gomez, Rosy; Basu, Rahul; Hong, Jung Joo; Labranche, Celia; Montefiori, David C; Villinger, Francois; Moss, Bernard; Amara, Rama Rao

    2015-08-01

    The goal of an HIV vaccine is to generate robust and durable protective Ab. Vital to this goal is the induction of CD4(+) T follicular helper (TFH) cells. However, very little is known about the TFH response to HIV vaccination and its relative contribution to magnitude and quality of vaccine-elicited Ab titers. In this study, we investigated these questions in the context of a DNA/modified vaccinia virus Ankara SIV vaccine with and without gp140 boost in aluminum hydroxide in rhesus macaques. In addition, we determined the frequency of vaccine-induced CD4(+) T cells coexpressing chemokine receptor, CXCR5 (facilitates migration to B cell follicles) in blood and whether these responses were representative of lymph node TFH responses. We show that booster modified vaccinia virus Ankara immunization induced a distinct and transient accumulation of proliferating CXCR5(+) and CXCR5(-) CD4 T cells in blood at day 7 postimmunization, and the frequency of the former but not the latter correlated with TFH and B cell responses in germinal centers of the lymph node. Interestingly, gp140 boost induced a skewing toward CXCR3 expression on germinal center TFH cells, which was strongly associated with longevity, avidity, and neutralization potential of vaccine-elicited Ab response. However, CXCR3(+) cells preferentially expressed the HIV coreceptor CCR5, and vaccine-induced CXCR3(+)CXCR5(+) cells showed a moderate positive association with peak viremia following SIV251 infection. Taken together, our findings demonstrate that vaccine regimens that elicit CXCR3-biased TFH cell responses favor Ab persistence and avidity but may predispose to higher acute viremia in the event of breakthrough infections. PMID:26116502

  4. A new genetic vaccine platform based on an adeno-associated virus isolated from a rhesus macaque.

    Science.gov (United States)

    Lin, Jianping; Calcedo, Roberto; Vandenberghe, Luk H; Bell, Peter; Somanathan, Suryanarayan; Wilson, James M

    2009-12-01

    We created a hybrid adeno-associated virus (AAV) from two related rhesus macaque isolates, called AAVrh32.33, and evaluated it as a vaccine carrier for human immunodeficiency virus type 1 (HIV-1) and type A influenza virus antigens. The goal was to overcome the limitations of vaccines based on other AAVs, which generate dysfunctional T-cell responses and are inhibited by antibodies found in human sera. Injection of a Gag-expressing AAVrh32.33 vector into mice resulted in a high-quality CD8(+) T-cell response. The resulting Gag-specific T cells express multiple cytokines at high levels, including interleukin-2, with many having memory phenotypes; a subsequent boost with an adenovirus vector yielded a brisk expansion of Gag-specific T cells. A priming dose of AAVrh32.33 led to high levels of Gag antibodies, which exceed levels found after injection of adenovirus vectors. Importantly, passive transfer of pooled human immunoglobulin into mice does not interfere with the efficacy of AAVrh32.33 expressing nucleoproteins from influenza virus, as measured by protection to a lethal dose of influenza virus, which is consistent with the very low seroprevalence to this virus in humans. Studies of macaques with vectors expressing gp140 from HIV-1 (i.e., with AAVrh32.33 as the prime and simian adenovirus type 24 as the boost) demonstrated results similar to those for mice with high-level and high-quality CD8(+) T-cell responses to gp140 and high-titered neutralizing antibodies to homologous HIV-1. The biology of this novel AAV hybrid suggests that it should be a preferred genetic vaccine carrier, capable of generating robust T- and B-cell responses. PMID:19812149

  5. Fusion proteins of HIV-1 envelope glycoprotein gp120 with CD4-induced antibodies showed enhanced binding to CD4 and CD4 binding site antibodies

    International Nuclear Information System (INIS)

    Highlights: ► Some recombinant HIV-1 gp120s do not preserve their conformations on gp140s. ► We hypothesize that CD4i antibodies could induce conformational changes in gp120. ► CD4i antibodies enhance binding of CD4 and CD4bs antibodies to gp120. ► CD4i antibody-gp120 fusion proteins could have potential as vaccine immunogens. -- Abstract: Development of successful AIDS vaccine immunogens continues to be a major challenge. One of the mechanisms by which HIV-1 evades antibody-mediated neutralizing responses is the remarkable conformational flexibility of its envelope glycoprotein (Env) gp120. Some recombinant gp120s do not preserve their conformations on gp140s and functional viral spikes, and exhibit decreased recognition by CD4 and neutralizing antibodies. CD4 binding induces conformational changes in gp120 leading to exposure of the coreceptor-binding site (CoRbs). In this study, we test our hypothesis that CD4-induced (CD4i) antibodies, which target the CoRbs, could also induce conformational changes in gp120 leading to better exposed conserved neutralizing antibody epitopes including the CD4-binding site (CD4bs). We found that a mixture of CD4i antibodies with gp120 only weakly enhanced CD4 binding. However, such interactions in single-chain fusion proteins resulted in gp120 conformations which bound to CD4 and CD4bs antibodies better than the original or mutagenically stabilized gp120s. Moreover, the two molecules in the fusion proteins synergized with each other in neutralizing HIV-1. Therefore, fusion proteins of gp120 with CD4i antibodies could have potential as components of HIV-1 vaccines and inhibitors of HIV-1 entry, and could be used as reagents to explore the conformational flexibility of gp120 and mechanisms of entry and immune evasion.

  6. Thermostability of Well-Ordered HIV Spikes Correlates with the Elicitation of Autologous Tier 2 Neutralizing Antibodies

    Science.gov (United States)

    Bale, Shridhar; Kumar, Shailendra; Guenaga, Javier; Wilson, Richard; de Val, Natalia; Arendt, Heather; DeStefano, Joanne; Ward, Andrew B.; Wyatt, Richard T.

    2016-01-01

    In the context of HIV vaccine design and development, HIV-1 spike mimetics displaying a range of stabilities were evaluated to determine whether more stable, well-ordered trimers would more efficiently elicit neutralizing antibodies. To begin, in vitro analysis of trimers derived from the cysteine-stabilized SOSIP platform or the uncleaved, covalently linked NFL platform were evaluated. These native-like trimers, derived from HIV subtypes A, B, and C, displayed a range of thermostabilities, and were “stress-tested” at varying temperatures as a prelude to in vivo immunogenicity. Analysis was performed both in the absence and in the presence of two different adjuvants. Since partial trimer degradation was detected at 37°C before or after formulation with adjuvant, we sought to remedy such an undesirable outcome. Cross-linking (fixing) of the well-ordered trimers with glutaraldehyde increased overall thermostability, maintenance of well-ordered trimer integrity without or with adjuvant, and increased resistance to solid phase-associated trimer unfolding. Immunization of unfixed and fixed well-ordered trimers into animals revealed that the elicited tier 2 autologous neutralizing activity correlated with overall trimer thermostability, or melting temperature (Tm). Glutaraldehyde fixation also led to higher tier 2 autologous neutralization titers. These results link retention of trimer quaternary packing with elicitation of tier 2 autologous neutralizing activity, providing important insights for HIV-1 vaccine design. PMID:27487086

  7. Codon preference is but an illusion created by the construction principle of coding sequences.

    OpenAIRE

    Ohno, S.

    1988-01-01

    Modern coding sequences are in the periodicto-chaotic transition. In the case of two related sequences for lens alpha A-crystallin and small heat shock protein, the original repeating units were heptameric in length. Accordingly, base trimers that were parts of heptameric units recurred far more frequently than those that were not included. In the crystallin coding sequence, CTG trimer recurred 21 times, and TCT and TCC trimers recurred 17 times each. By contrast, CTA and TCG, although relate...

  8. Human synaptic plasticity gene expression profile and dendritic spine density changes in HIV-infected human CNS cells: role in HIV-associated neurocognitive disorders (HAND.

    Directory of Open Access Journals (Sweden)

    Venkata Subba Rao Atluri

    Full Text Available HIV-associated neurocognitive disorders (HAND is characterized by development of cognitive, behavioral and motor abnormalities, and occur in approximately 50% of HIV infected individuals. Our current understanding of HAND emanates mainly from HIV-1 subtype B (clade B, which is prevalent in USA and Western countries. However very little information is available on neuropathogenesis of HIV-1 subtype C (clade C that exists in Sub-Saharan Africa and Asia. Therefore, studies to identify specific neuropathogenic mechanisms associated with HAND are worth pursuing to dissect the mechanisms underlying this modulation and to prevent HAND particularly in clade B infection. In this study, we have investigated 84 key human synaptic plasticity genes differential expression profile in clade B and clade C infected primary human astrocytes by using RT(2 Profile PCR Array human Synaptic Plasticity kit. Among these, 31 and 21 synaptic genes were significantly (≥3 fold down-regulated and 5 genes were significantly (≥3 fold up-regulated in clade B and clade C infected cells, respectively compared to the uninfected control astrocytes. In flow-cytometry analysis, down-regulation of postsynaptic density and dendrite spine morphology regulatory proteins (ARC, NMDAR1 and GRM1 was confirmed in both clade B and C infected primary human astrocytes and SK-N-MC neuroblastoma cells. Further, spine density and dendrite morphology changes by confocal microscopic analysis indicates significantly decreased spine density, loss of spines and decreased dendrite diameter, total dendrite and spine area in clade B infected SK-N-MC neuroblastoma cells compared to uninfected and clade C infected cells. We have also observed that, in clade B infected astrocytes, induction of apoptosis was significantly higher than in the clade C infected astrocytes. In conclusion, this study suggests that down-regulation of synaptic plasticity genes, decreased dendritic spine density and induction of

  9. Species Differences in the Carbohydrate Binding Preferences of Surfactant Protein D

    DEFF Research Database (Denmark)

    Crouch, Erika C.; Smith, Kelly; McDonald, Barbara; Briner, David; Linders, Bruce; McDonald, Joseph; Holmskov, Uffe; Head, James; Hartshorn, Kevan

    2006-01-01

    Interactions of surfactant protein D (SP-D) with micro-organisms and organic antigens involve binding to the trimeric neck plus carbohydrate recognition domain (neck+CRD). In these studies, we compared the ligand binding of homologous human, rat, and mouse trimeric neck+CRD fusion proteins, each...

  10. U.S. EPA’s Technical Support for the Reich Farm (Toms River, NJ) Superfund Site Remediation

    Science.gov (United States)

    PowerPoint slide file that gives a brief history of the SAN Trimer contamination in Toms River, NJ as well as the EPA's provided technical support, specifically the development and application of the Provisional Peer-Reviewed Toxicity Value (PPRTV) assessment for SAN Trimer.

  11. Phylogenetic Analysis of Staphylococcus aureus CC398 Reveals a Sub-Lineage Epidemiologically Associated with Infections in Horses

    DEFF Research Database (Denmark)

    Abdelbary, Mohamed M. H.; Wittenberg, Anne; Cuny, Christiane;

    2014-01-01

    -allelic polymorphisms, and phylogenetic analyses revealed that an epidemic sub-clone within CC398 (dubbed 'clade (C)') has spread within and between equine hospitals, where it causes nosocomial infections in horses and colonises the personnel. While clade (C) was strongly associated with S. aureus from horses...... in veterinary-care settings (p = 2x10(-7)), it remained extremely rare among S. aureus isolates from human infections.......In the early 2000s, a particular MRSA clonal complex (CC398) was found mainly in pigs and pig farmers in Europe. Since then, CC398 has been detected among a wide variety of animal species worldwide. We investigated the population structure of CC398 through mutation discovery at 97 genetic...

  12. Posttranslational Modification of α-Dystroglycan, the Cellular Receptor for Arenaviruses, by the Glycosyltransferase LARGE Is Critical for Virus Binding

    OpenAIRE

    Kunz, Stefan; Rojek, Jillian M.; Kanagawa, Motoi; Spiropoulou, Christina F.; Barresi, Rita; Campbell, Kevin P.; Oldstone, Michael B A

    2005-01-01

    The receptor for lymphocytic choriomeningitis virus (LCMV), the human pathogenic Lassa fever virus (LFV), and clade C New World arenaviruses is α-dystroglycan (α-DG), a cell surface receptor for proteins of the extracellular matrix (ECM). Specific posttranslational modification of α-DG by the glycosyltransferase LARGE is critical for its function as an ECM receptor. In the present study, we show that LARGE-dependent modification is also crucial for α-DG's function as a cellular receptor for a...

  13. Alterations in Natural Killer Cell Receptor Profiles During HIV Type 1 Disease Progression Among Chronically Infected South African Adults

    OpenAIRE

    Wong, Ambrose H.W.; Williams, Katie; Reddy, Sharon; Wilson, Douglas; Giddy, Janet; Alter, Galit; Ghebremichael, Musie; Carrington, Mary N; Ndung'u, Thumbi; Walker, Bruce D.; Altfeld, Marcus; Carr, William H.

    2010-01-01

    Recent studies suggest that innate immune responses by natural killer (NK) cells play a significant role in restricting human immunodeficiency virus type-1 (HIV-1) pathogenesis. Our aim was to characterize changes in NK cells associated with HIV-1 clade C disease progression. Here we used multiparametric flow cytometry (LSRII) to quantify phenotype and function of NK cells in a cross-sectional analysis of cryopreserved blood samples from a cohort of 41 chronically HIV-1-infected, treatment-na...

  14. A single amino acid substitution in the C4 region in gp120 confers enhanced neutralization of HIV-1 by modulating CD4 binding sites and V3 loop

    OpenAIRE

    Ringe, Rajesh; Sharma, Deepak; Zolla-Pazner, Susan; Phogat, Sanjay; Risbud, Arun; Thakar, Madhuri; Paranjape, Ramesh; Bhattacharya, Jayanta

    2011-01-01

    Identification of vulnerability in the HIV-1 envelope (Env) will aid in Env-based vaccine design. We recently found an HIV-1 clade C Env clone (4-2.J45) amplified from a recently infected Indian patient showing exceptional neutralization sensitivity to autologous plasma in contrast to other autologous Envs obtained at the same time point. By constructing chimeric Envs and fine mapping between sensitive and resistant Env clones, we found that substitution of highly conserved isoleucine (I) wit...

  15. Bleaching susceptibility and mortality of corals are determined by fine-scale differences in symbiont type

    OpenAIRE

    Sampayo, E.M.; Ridgway, T.; Bongaerts, P.; Hoegh-Guldberg, O

    2008-01-01

    Coral bleaching has been identified as one of the major contributors to coral reef decline, and the occurrence of different symbionts determined by broad genetic groupings (clades A–H) is commonly used to explain thermal responses of reef-building corals. By using Stylophora pistillata as a model, we monitored individual tagged colonies in situ over a two-year period and show that fine level genetic variability within clade C is correlated to differences in bleaching susceptibility. Based on ...

  16. Growth tradeoffs associated with thermotolerant symbionts in the coral Pocillopora damicornis are lost in warmer oceans

    Science.gov (United States)

    Cunning, R.; Gillette, P.; Capo, T.; Galvez, K.; Baker, A. C.

    2015-03-01

    The growth and survival of reef corals are influenced by their symbiotic algal partners ( Symbiodinium spp.), which may be flexible in space and time. Tradeoffs among partnerships exist such that corals with thermotolerant symbionts (e.g., clade D) resist bleaching but grow more slowly, making the long-term ecosystem-level impacts of different host-symbiont associations uncertain. However, much of this uncertainty is due to limited data regarding these tradeoffs and particularly how they are mediated by the environment. To address this knowledge gap, we measured growth and survival of Pocillopora damicornis with thermally sensitive (clade C) or tolerant (clade D) symbionts at three temperatures over 18-55 weeks. Warming reduced coral growth overall, but altered the tradeoffs associated with symbiont type. While clade D corals grew 35-40 % slower than clade C corals at cooler temperatures (26 °C), warming of 1.5-3 °C reduced and eliminated this growth disadvantage. These results suggest that although warmer oceans will negatively impact corals, clade D may enhance survival at no cost to growth relative to clade C. Understanding these genotype-environment interactions can help improve modeling efforts and conservation strategies for reefs under global climate change.

  17. Restriction Fragment Length Polymorphism Analysis of Large Subunit rDNA of Symbiotic Dinoflagellates from Scleractinian Corals in the Zhubi Coral Reef of the Nansha Islands

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Zooxanthellae are very important for the coral reef ecosystem. The diversity of coral hosts is high in the South China Sea, but the diversity of zooxanthellae has not yet been investigated. We chose the Zhubi Coral Reef of the Nansha Islands as the region to be surveyed in the present study because it represents a typical tropical coral reef of the South China Sea and we investigated zooxanthellae diversity in 10 host scleractinian coral species using polymerase chain reaction (PCR) of the large subunit rRNA and restriction fragment length polymorphism (RFLP) patterns. Pocillopora verrucosa, Acropora pelifera, Acropora millepora, Fungia fungites, Galaxea fascicularis, and Acropora pruinosa harbor Clade C, Goniastrea aspera harbors Clade D, and Acropora formosa harbors Clades D and C. Therefore, the Clade C is the dominant type in the Zhubi Coral Reef of the NanshaIslands. Furthermore, the results of the present also disprove what has been widely accepted, namely that one coral host harbors only one algal symbiont. The coral-algal symbiosis is flexible, which may be an important mechanism for surviving coral bleaching. Meanwhile, on the basis of the results of the present study, we think that Symbiodinium Clade D may be more tolerant to stress than Symbiodinium Clade C.

  18. Three-body bound states in finite volume with EFT

    International Nuclear Information System (INIS)

    Three particles with large scattering length display a universal spectrum of three-body bound states called ''Efimov trimers''. We calculate the modification of the Efimov trimers of three identical bosons in a finite cubic box and compute the dependence of their energies on the box size using effective field theory. The renormalization of the effective field theory in the finite volume is explicitly verified. We investigate the effects of partial wave mixing and study the behavior of shallow trimers near the dimer energy. Finally, we present first results for the triton in a finite volume.

  19. Hydrogen ions directly regulating the oligomerization state of Photosystem I in intact Spirulina platensis cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    H+ concentration induced-monomerization or trimerization of photosystem I (PSI) in cyanobacteria has never been directly observed. In this work, taking characteristic spectra for the trimers and monomers as the indicators, it was experimentally demonstrated that H+ could induce the oligomeric changes of PSI reaction centers in the intact Spirulina ,platensis cells and also in the isolated thylakoid membrane complexes. Especially, the higher concentration of H+ would induce the monomerization while the lower the trimerization, suggesting the electrostatic interaction should be mainly responsible forchanges in the oligomeric state of PSI in Spirulina platensis.

  20. Self-poling with oxygen off-stoichiometry in ferroelectric hexagonal manganites

    Directory of Open Access Journals (Sweden)

    Xueyun Wang

    2015-04-01

    Full Text Available Topological vortices with complex domains and domain walls exist in hexagonal manganites, which undergo a structural transition accompanying ferroelectric polarization and trimerization. We have systematically studied the origin of two different types (type-I and type-II of vortex domains with controlled oxygen stoichiometry and found that the evolution between type-I and type-II vortex domains and the presence of charged walls between two different trimerization antiphase domains result from an oxygen vacancy gradient. We have also discovered a rare phenomenon of vortex core split, which appears to stem from the instability of charged ferroelectric walls between domains with the same trimerization antiphase.

  1. Analysis of Overlapped and Noisy Hydrogen/Deuterium Exchange Mass Spectra

    Science.gov (United States)

    Guttman, Miklos; Weis, David D.; Engen, John R.; Lee, Kelly K.

    2013-12-01

    Noisy and overlapped mass spectrometry data hinder the sequence coverage that can be obtained from hydrogen deuterium exchange analysis, and places a limit on the complexity of the samples that can be studied by this technique. Advances in instrumentation have addressed these limits, but as the complexity of the biological samples under investigation increases, these problems are re-encountered. Here we describe the use of binomial distribution fitting with asymmetric linear squares regression for calculating the accurate deuterium content for mass envelopes of low signal or that contain significant overlap. The approach is demonstrated with a test data set of HIV Env gp140 wherein inclusion of the new analysis regime resulted in obtaining exchange data for 42 additional peptides, improving the sequence coverage by 11 %. At the same time, the precision of deuterium uptake measurements was improved for nearly every peptide examined. The improved processing algorithms also provide an efficient method for deconvolution of bimodal mass envelopes and EX1 kinetic signatures. All these functions and visualization tools have been implemented in the new version of the freely available software, HX-Express v2.

  2. Gp120 on HIV-1 Virions Lacks O-Linked Carbohydrate.

    Science.gov (United States)

    Stansell, Elizabeth; Panico, Maria; Canis, Kevin; Pang, Poh-Choo; Bouché, Laura; Binet, Daniel; O'Connor, Michael-John; Chertova, Elena; Bess, Julian; Lifson, Jeffrey D; Haslam, Stuart M; Morris, Howard R; Desrosiers, Ronald C; Dell, Anne

    2015-01-01

    As HIV-1-encoded envelope protein traverses the secretory pathway, it may be modified with N- and O-linked carbohydrate. When the gp120s of HIV-1 NL4-3, HIV-1 YU2, HIV-1 Bal, HIV-1 JRFL, and HIV-1 JRCSF were expressed as secreted proteins, the threonine at consensus position 499 was found to be O-glycosylated. For SIVmac239, the corresponding threonine was also glycosylated when gp120 was recombinantly expressed. Similarly-positioned, highly-conserved threonines in the influenza A virus H1N1 HA1 and H5N1 HA1 envelope proteins were also found to carry O-glycans when expressed as secreted proteins. In all cases, the threonines were modified predominantly with disialylated core 1 glycans, together with related core 1 and core 2 structures. Secreted HIV-1 gp140 was modified to a lesser extent with mainly monosialylated core 1 O-glycans, suggesting that the ectodomain of the gp41 transmembrane component may limit the accessibility of Thr499 to glycosyltransferases. In striking contrast to these findings, gp120 on purified virions of HIV-1 Bal and SIV CP-MAC lacked any detectable O-glycosylation of the C-terminal threonine. Our results indicate the absence of O-linked carbohydrates on Thr499 as it exists on the surface of virions and suggest caution in the interpretation of analyses of post-translational modifications that utilize recombinant forms of envelope protein. PMID:25915761

  3. Cluster Mean-Field Signature of Entanglement Entropy in Bosonic Superfluid-Insulator Transitions

    CERN Document Server

    Zhang, Li; Ke, Yongguan; Lee, Chaohong

    2016-01-01

    Entanglement entropy (EE), a fundamental conception in quantum information for characterizing entanglement, has been extensively employed to explore quantum phase transitions (QPTs). Although the conventional single-site mean-field (MF) approach successfully predicts the emergence of QPTs, it fails to include any entanglement. Here, for the first time, in the framework of a cluster MF treatment, we extract the signature of EE in the bosonic superfluid-insulator transitions. We consider a trimerized Kagome lattice of interacting bosons, in which each trimer is treated as a cluster, and implement the cluster MF treatment by decoupling all inter-trimer hopping. In addition to superfluid and integer insulator phases, we find that fractional insulator phases appear when the tunneling is dominated by the intra-trimer part. To quantify the residual bipartite entanglement in a cluster, we calculate the second-order Renyi entropy, which can be experimentally measured by quantum interference of many-body twins. The sec...

  4. Biomineralization of a Cadmium Chloride Nanocrystal by a Designed Symmetrical Protein.

    Science.gov (United States)

    Voet, Arnout R D; Noguchi, Hiroki; Addy, Christine; Zhang, Kam Y J; Tame, Jeremy R H

    2015-08-17

    We have engineered a metal-binding site into the novel artificial β-propeller protein Pizza. This new Pizza variant carries two nearly identical domains per polypeptide chain, and forms a trimer with three-fold symmetry. The designed single metal ion binding site lies on the symmetry axis, bonding the trimer together. Two copies of the trimer associate in the presence of cadmium chloride in solution, and very high-resolution X-ray crystallographic analysis reveals a nanocrystal of cadmium chloride, sandwiched between two trimers of the protein. This nanocrystal, containing seven cadmium ions lying in a plane and twelve interspersed chloride ions, is the smallest reported to date. Our results indicate the feasibility of using rationally designed symmetrical proteins to biomineralize nanocrystals with useful properties. PMID:26136355

  5. Ab initio study of atomic disorder on As-rich GaAs(111)A surface

    Science.gov (United States)

    Romanyuk, O.; Mutombo, P.; Grosse, F.

    2015-11-01

    Mechanisms for the appearance of disorder on the As-rich GaAs(111)A surface were investigated employing density functional theory (DFT). Focus was given to the As trimer interactions by considering different surface symmetries and rest site occupations. The (2 × 2) and the c(4 × 2) structure models with As trimer and an As rest site were found the most energetically stable under the As-rich experimental conditions at T = 0 K. Low interactions between neighboring As trimers causes disorder in thermodynamic equilibrium at finite temperatures. A careful analysis of the configurational entropy contributions including the different statistics was carried out. The experimentally observed As-rich (2 × 2) structure was confirmed to be kinetically stabilized. The stabilization mechanism is discussed with respect to the As trimer migration on the surface, which is limited by a large diffusion barrier through the As rest sites.

  6. Coil-type Fano Resonances: a Plasmonic Approach to Magnetic Sub-diffraction Confinement

    KAUST Repository

    Panaro, Simone

    2015-05-10

    Matrices of nanodisk trimers are introduced as plasmonic platforms for the generation of localized magnetic hot-spots. In Fano resonance condition, the optical magnetic fields can be squeezed in sub-wavelength regions, opening promising scenarios for spintronics.

  7. Electrophoretic analysis of the major outer membrane protein of Chlamydia psittaci reveals multimers which are recognized by protective monoclonal antibodies.

    OpenAIRE

    McCafferty, M C; Herring, A J; Andersen, A A; Jones, G. E.

    1995-01-01

    Purified major outer membrane protein, detergent solubilized and reduced with dithiothreitol but not heated, gave an apparent molecular weight in sodium dodecyl sulfate (SDS)-polyacrylamide gels almost three times that observed for the heat-denatured SDS-treated peptide. This is similar to the behavior of porin trimers from gram-negative bacteria. Two protective monoclonal antibodies showed strong binding to the proposed trimer but not to denatured, monomeric major outer membrane protein.

  8. Stoichiometry of Murine Leukemia Virus Envelope Protein-Mediated Fusion and Its Neutralization▿

    OpenAIRE

    Ou, Wu; Silver, Jonathan

    2006-01-01

    Envelope glycoproteins (Envs) of retroviruses form trimers that mediate fusion between viral and cellular membranes and are the targets for neutralizing antibodies. Understanding in detail how Env trimers mediate membrane fusion, and how antibodies interfere with this process, is a fundamental problem in biology with practical implications for the development of antiviral drugs and vaccines. We investigated the stoichiometry of Env-mediated fusion and its inhibition by antibody by inserting a...

  9. MOLECULAR DYNAMICS SIMULATIONS OF THE FULL TRIPLE HELICAL REGION OF COLLAGEN TYPE I PROVIDE AN ATOMIC SCALE VIEW OF THE PROTEIN’S REGIONAL HETEROGENEITY

    OpenAIRE

    Bodian, Dale L.; Radmer, Randall J.; HOLBERT, SEAN; Klein, Teri E.

    2011-01-01

    Collagen is a ubiquitous extracellular matrix protein. Its biological functions, including maintenance of the structural integrity of tissues, depend on its multiscale, hierarchical structure. Three elongated, twisted peptide chains of >1000 amino acids each assemble into trimeric proteins characterized by the defining triple helical domain. The trimers associate into fibrils, which pack into fibers. We conducted a 10 ns molecular dynamics simulation of the full-length triple helical domain, ...

  10. Universal bosonic tetramers of dimer-atom-atom structure

    OpenAIRE

    Deltuva, A.

    2012-01-01

    Unstable four-boson states having an approximate dimer-atom-atom structure are studied using momentum-space integral equations for the four-particle transition operators. For a given Efimov trimer the universal properties of the lowest associated tetramer are determined. The impact of this tetramer on the atom-trimer and dimer-dimer collisions is analyzed. The reliability of the three-body dimer-atom-atom model is studied.

  11. Characterization of Pgp3, a Chlamydia trachomatis Plasmid-Encoded Immunodominant Antigen▿

    OpenAIRE

    Chen, Ding; Lei, Lei; Lu, Chunxue; Galaleldeen, Ahmad; Hart, P. John; Zhong, Guangming

    2010-01-01

    Human antibody recognition of Chlamydia trachomatis plasmid-encoded Pgp3 protein is dependent on the native conformation of Pgp3. The structural basis for the conformation dependence and the function of Pgp3 remain unknown. Here, we report that Pgp3 trimerization is required for the recognition of Pgp3 by human antibodies. In a native polyacrylamide gel, Pgp3 purified from a bacterial expression system migrated as stable trimers that were dissociated into monomers only by treatment with urea ...

  12. The Free Energy of Dissociation of Oligomeric Structure in Phycocyanin is not Linear with Denaturant†

    OpenAIRE

    Thoren, Katie L.; Connell, Katelyn B.; Robinson, Taylor E.; Shellhamer, David D.; Tammaro, Margaret S.; Gindt, Yvonne M.

    2006-01-01

    Using SEC HPLC and fluorescence anisotropy, absorption spectra were assigned to the specific oligomeric structures found with phycocyanin. The absorption spectra were used to quantify the population of each oligomeric form of the protein as a function of both urea concentration and temperature. Phycocyanin hexamer dissociate to trimers with equilibrium constants of 10−6 to 10−5. Phycocyanin trimers dissociate to monomers with equilibrium constants of 10−15 to 10−12. Both dissociation constant...

  13. Detection of DNA hybridizations using solid-state nanopores

    OpenAIRE

    Balagurusamy, Venkat S K; Weinger, Paul; Ling, Xinsheng Sean

    2010-01-01

    We report an experimental study of using DNA translocation through solid-state nanopores to detect the sequential arrangement of two double-stranded 12-mer hybridization segments on a single-stranded DNA molecule. The sample DNA is a trimer molecule formed by hybridizing three single-stranded oligonucleotides. A polystyrene bead is attached to the end of the trimer DNA, providing a mechanism in slowing down the translocation and suppressing the thermal diffusion, thereby allowing the detectio...

  14. Hantavirus N Protein Exhibits Genus-Specific Recognition of the Viral RNA Panhandle▿

    OpenAIRE

    Mir, M A; Brown, B.; Hjelle, B; Duran, W. A.; Panganiban, A T

    2006-01-01

    A key genomic characteristic that helps define Hantavirus as a genus of the family Bunyaviridae is the presence of distinctive terminal complementary nucleotides that promote the folding of the viral genomic segments into “panhandle” hairpin structures. The hantavirus nucleocapsid protein (N protein), which is encoded by the smallest of the three negative-sense genomic RNA segments, undergoes in vivo and in vitro trimerization. Trimeric hantavirus N protein specifically recognizes the panhand...

  15. A Ser29Leu substitution in the cytosine deaminase Fca1p is responsible for clade-specific flucytosine resistance in Candida dubliniensis.

    LENUS (Irish Health Repository)

    McManus, Brenda A

    2009-11-01

    The population structure of the opportunistic yeast pathogen Candida dubliniensis is composed of three main multilocus sequence typing clades (clades C1 to C3), and clade C3 predominantly consists of isolates from the Middle East that exhibit high-level resistance (MIC(50) > or = 128 microg\\/ml) to the fungicidal agent flucytosine (5FC). The close relative of C. dubliniensis, C. albicans, also exhibits clade-specific resistance to 5FC, and resistance is most commonly mediated by an Arg101Cys substitution in the FUR1 gene encoding uracil phosphoribosyltransferase. Broth microdilution assays with fluorouracil (5FU), the toxic deaminated form of 5FC, showed that both 5FC-resistant and 5FC-susceptible C. dubliniensis isolates exhibited similar 5FU MICs, suggesting that the C. dubliniensis cytosine deaminase (Fca1p) encoded by C. dubliniensis FCA1 (CdFCA1) may play a role in mediating C. dubliniensis clade-specific 5FC resistance. Amino acid sequence analysis of the CdFCA1 open reading frame (ORF) identified a homozygous Ser29Leu substitution in all 12 5FC-resistant isolates investigated which was not present in any of the 9 5FC-susceptible isolates examined. The tetracycline-inducible expression of the CdFCA1 ORF from a 5FC-susceptible C. dubliniensis isolate in two separate 5FC-resistant clade C3 isolates restored susceptibility to 5FC, demonstrating that the Ser29Leu substitution was responsible for the clade-specific 5FC resistance and that the 5FC resistance encoded by FCA1 genes with the Ser29Leu transition is recessive. Quantitative real-time PCR analysis showed no significant difference in CdFCA1 expression between 5FC-susceptible and 5FC-resistant isolates in either the presence or the absence of subinhibitory concentrations of 5FC, suggesting that the Ser29Leu substitution in the CdFCA1 ORF is the sole cause of 5FC resistance in clade C3 C. dubliniensis isolates.

  16. Genetic variability of the coat protein sequence of pea seed-borne mosaic virus isolates and the current relationship between phylogenetic placement and resistance groups.

    Science.gov (United States)

    Wylie, S J; Coutts, B A; Jones, R A C

    2011-07-01

    Nucleotide sequences of complete or partial coat protein (CP) genes were determined for 11 isolates of pea seed-borne mosaic virus (PSbMV) from Australia and one from China, and compared with known sequences of 20 other isolates. On phylogenetic analysis, the isolates from Australia and China grouped into 2 of 3 clades. Clade A contained three sub-clades (Ai, Aii and Aiii), Australian isolates were in Ai or Aiii, and the Chinese isolate in Aii. Clade A contained isolates in pathotypes P-1, P-2 and U-2; clade B, one isolate in P-2; and clade C, only isolates in P-4. PMID:21519930

  17. Evidence of Sympatry of Clade A and Clade B Head Lice in a Pre-Columbian Chilean Mummy from Camarones

    Science.gov (United States)

    Boutellis, Amina; Drali, Rezak; Rivera, Mario A.; Mumcuoglu, Kosta Y.; Raoult, Didier

    2013-01-01

    Three different lineages of head lice are known to parasitize humans. Clade A, which is currently worldwide in distribution, was previously demonstrated to be present in the Americas before the time of Columbus. The two other types of head lice are geographically restricted to America and Australia for clade B and to Africa and Asia for clade C. In this study, we tested two operculated nits from a 4,000-year-old Chilean mummy of Camarones for the presence of the partial Cytb mitochondrial gene (270 bp). Our finding shows that clade B head lice were present in America before the arrival of the European colonists. PMID:24204678

  18. Vaccine Induction of Lymph Node-Resident Simian Immunodeficiency Virus Env-Specific T Follicular Helper Cells in Rhesus Macaques.

    Science.gov (United States)

    Vargas-Inchaustegui, Diego A; Demers, Andrew; Shaw, Julia M; Kang, Guobin; Ball, David; Tuero, Iskra; Musich, Thomas; Mohanram, Venkatramanan; Demberg, Thorsten; Karpova, Tatiana S; Li, Qingsheng; Robert-Guroff, Marjorie

    2016-02-15

    Measurement of Ag-specific T follicular helper (TFH) cell activity in rhesus macaques has not previously been reported. Given that rhesus macaques are the animal model of choice for evaluating protective efficacy of HIV/SIV vaccine candidates and that TFH cells play a pivotal role in aiding B cell maturation, quantifying vaccine induction of HIV/SIV-specific TFH cells would greatly benefit vaccine development. In this study, we quantified SIV Env-specific IL-21-producing TFH cells for the first time, to our knowledge, in a nonhuman primate vaccine study. Macaques were primed twice mucosally with adenovirus 5 host range mutant recombinants encoding SIV Env, Rev, Gag, and Nef followed by two i.m. boosts with monomeric SIV gp120 or oligomeric SIV gp140 proteins. At 2 wk after the second protein boost, we obtained lymph node biopsy specimens and quantified the frequency of total and SIV Env-specific IL-21(+) TFH cells and total germinal center B cells, the size and number of germinal centers, and the frequency of SIV-specific Ab-secreting cells in B cell zones. Multiple correlation analyses established the importance of TFH for development of B cell responses in systemic and mucosally localized compartments, including blood, bone marrow, and rectum. Our results suggest that the SIV-specific TFH cells, initially induced by replicating adenovirus-recombinant priming, are long lived. The multiple correlations of SIV Env-specific TFH cells with systemic and mucosal SIV-specific B cell responses indicate that this cell population should be further investigated in HIV vaccine development as a novel correlate of immunity. PMID:26773147

  19. Microprocessor-controlled vs. "dump-freezing" platelet and lymphocyte cryopreservation: A quantitative and qualitative comparative study

    Directory of Open Access Journals (Sweden)

    Balint Bela

    2006-01-01

    Full Text Available Background/Aim. Thermodynamical and cryobiological parameters responsible for cell damages during cryopreservation (cryoinjuries have not yet been completely explained. Thus, freezing procedures should be revised, exactly optimized to obtain an enhanced structural and functional recovery of frozen- thawed cells. The aim of this study was to compare microprocessor- controlled (controlled-rate with the compensation of the released fusion heat and “dump-freezing” (uncontrolled- rate of the platelet and lymphocyte cryopreservation efficacy. Methods. Platelet quantitative recovery (post-thaw vs. unfrozen cell count, viability (using hypotonic shock response - HSR, morphological score (PMS, ultrastructural (electron microscopy properties and expression of different surface antigens were investigated. In lymphocyte setting, cell recovery and viability (using trypan blue exclusion test as well as functionality (by plant mitogens were determined. Controlled- rate freezing and uncontrolled-rate cryopreservation were combined with 6% (platelets and 10% (lymphocytes dimethyl sulfoxide (DMSO. Results. Platelet recovery and functionality were superior in the controlled-rate system. The majority of surface antigen expression was reduced in both freezing groups vs. unfrozen cells, but GP140/CD62p was significantly higher in controlled-rate vs. uncontrolled-rate setting. Controlled- rate freezing resulted with better lymphocyte recovery and viability (trypan blue-negative cell percentage. In mitogen-induced lymphocyte proliferative response no significant intergroup difference (controlled-rate vs. uncontrolled-rate were found. Conclusion. The data obtained in this study showned the dependence of cell response on the cryopreservation type. Controlled-rate freezing provided a superior platelet quantitative and functional recovery. Lymphocyte recovery and viability were better in the controlled-rate group, although only a minor intergroup difference for cell

  20. Amino-terminal domain of the v-fms oncogene product includes a functional signal peptide that directs synthesis of a transforming glycoprotein in the absence of feline leukemia virus gag sequences

    International Nuclear Information System (INIS)

    The nucleotide sequence of a 5' segment of the human genomic c-fms proto-oncogene suggested that recombination between feline leukemia virus and feline c-fms sequences might have occurred in a region encoding the 5' untranslated portion of c-fms mRNA. The polyprotein precursor gP180/sup gag-fms/ encoded by the McDonough strain of feline sarcoma virus was therefore predicted to contain 34 v-fms-coded amino acids derived from sequences of the c-fms gene that are not ordinarily translated from the proto-oncogene mRNA. The (gP180/sup gag-fms/) polyprotein was cotranslationally cleaved near the gag-fms junction to remove its gag gene-coded portion. Determination of the amino-terminal sequence of the resulting v-fms-coded glycoprotein, gp120/sup v-fms/, showed that the site of proteolysis corresponded to a predicted signal peptidase cleavage site within the c-fms gene product. Together, these analyses suggested that the linked gag sequences may not be necessary for expression of a biologically active v-fms gene product. The gag-fms sequences of feline sarcoma virus strain McDonough and the v-fms sequences alone were inserted into a murine retroviral vector containing a neomycin resistance gene. The authors conclude that a cryptic hydrophobic signal peptide sequence in v-fms was unmasked by gag deletion, thereby allowing the correct orientation and transport of the v-fms was unmasked by gag deletion, thereby allowing the correct orientation and transport of the v-fms gene product within membranous organelles. It seems likely that the proteolytic cleavage of gP180/gag-fms/ is mediated by signal peptidase and that the amino termini of gp140/sup v-fms/ and the c-fms gene product are identical

  1. Characterization of the Main Light-Harvesting Chlorophyll a/b-Protein Complex of Green Alga, Bryopsis corticulans

    Institute of Scientific and Technical Information of China (English)

    CHENHuil; SHENShi-Hua; GONGYan-Dao; HEJun-Fang; WANGGuang-Ce; LILiang-Bi; KUANGTing-Yun

    2004-01-01

    The main light-harvesting chlorophyll a/b -protein complex (LHC Ⅱ) has been isolated directly from thylakoid membranes of shiphonous 8Teen alga, Bryopsis corticulans Setch. by using two consecutive runs of anion exchange and gel-filtration chromatography. Monomeric and trimeric subcomplexes of LHC Ⅱ were obtained by using sucrose gradient ultracentrifugation. Pigment analysis by reversed-phase high performance liquid chromatography showed that chlorophyll a (Chl a), chlorophyll b (Chl b), neoxanthin, violaxanthin and siphonaxanthin were involved in LHC Ⅱ from B. corticulans. The properties of electronictransition of monomeric LHC Ⅱ showed similarities to those of trimeric LHC Ⅱ. Circular dichroism spectroscopy showed that strong intramolecular interaction of excitonic dipoles between Chl a and between Chl b exist in one LHC Ⅱ apoprotein, while the intermolecular interaction of these dipoles can be intensified in the trimeric structure. The monomer has high efficient energy transfer from Chl b and siphonaxanthin to Chl a similarly to that of the trimer. Our results suggest that in B. corticulans, LHC Ⅱ monomer has high ordered pigment organization that play effective physiological function as the trimer, and thus it might be also a functional organization existing in thylakoid membrane of B.corticulans.

  2. Studies on the X-Ray and Solution Structure of FeoB from Escherichia coli BL21.

    Science.gov (United States)

    Hagelueken, Gregor; Hoffmann, Jan; Schubert, Erik; Duthie, Fraser G; Florin, Nicole; Konrad, Lisa; Imhof, Diana; Behrmann, Elmar; Morgner, Nina; Schiemann, Olav

    2016-06-21

    The ferrous iron transporter FeoB is an important factor in the iron metabolism of many bacteria. Although several structural studies have been performed on its cytosolic GTPase domain (NFeoB), the full-length structure of FeoB remains elusive. Based on a crystal packing analysis that was performed on crystals of NFeoB, a trimeric structure of the FeoB channel was proposed, where the transport pore runs along the trimer axis. Because this trimer has not been observed in some subsequently solved structures of NFeoB homologs, it remains unclear whether or not the trimer is indeed functionally relevant. Here, pulsed electron-electron double resonance spectroscopy, negative stain electron microscopy, and native mass spectrometry are used to analyze the oligomeric state of different soluble and full-length FeoB constructs. The results show that the full-length protein is predominantly monomeric, whereas dimers and trimers are formed to a small percentage. Furthermore, the solution structure of the switch I region is analyzed by pulsed electron-electron double resonance spectroscopy and a new, to our knowledge, crystal structure of NFeoB from Escherichia coli BL21 is presented. PMID:27332122

  3. Activation and deactivation of vibronic channels in intact phycocyanin rods

    Science.gov (United States)

    Nganou, C.; David, L.; Meinke, R.; Adir, N.; Maultzsch, J.; Mkandawire, M.; Pouhè, D.; Thomsen, C.

    2014-02-01

    We investigated the excitation modes of the light-harvesting protein phycocyanin (PC) from Thermosynechococcus vulcanus in the crystalline state using UV and near-infrared Raman spectroscopy. The spectra revealed the absence of a hydrogen out-of-plane wagging (HOOP) mode in the PC trimer, which suggests that the HOOP mode is activated in the intact PC rod, while it is not active in the PC trimer. Furthermore, in the PC trimer an intense mode at 984 cm-1 is assigned to the C-C stretching vibration while the mode at 454 cm-1 is likely due to ethyl group torsion. In contrast, in the similar chromophore phytochromobilin the C5,10,15-D wag mode at 622 cm-1 does not come from a downshift of the HOOP. Additionally, the absence of modes between 1200 and 1300 cm-1 rules out functional monomerization. A correlation between phycocyanobilin (PCB) and phycoerythrobilin (PEB) suggests that the PCB cofactors of the PC trimer appear in a conformation similar to that of PEB. The conformation of the PC rod is consistent with that of the allophycocyanin (APC) trimer, and thus excitonic flow is facilitated between these two independent light-harvesting compounds. This excitonic flow from the PC rod to APC appears to be modulated by the vibration channels during HOOP wagging, C = C stretching, and the N-H rocking in-plan vibration.

  4. Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike

    Science.gov (United States)

    Lee, Jeong Hyun; Leaman, Daniel P.; Kim, Arthur S.; Torrents de La Peña, Alba; Sliepen, Kwinten; Yasmeen, Anila; Derking, Ronald; Ramos, Alejandra; de Taeye, Steven W.; Ozorowski, Gabriel; Klein, Florian; Burton, Dennis R.; Nussenzweig, Michel C.; Poignard, Pascal; Moore, John P.; Klasse, Per Johan; Sanders, Rogier W.; Zwick, Michael B.; Wilson, Ian A.; Ward, Andrew B.

    2015-09-01

    The recent identification of three broadly neutralizing antibodies (bnAbs) against gp120-gp41 interface epitopes has expanded the targetable surface on the HIV-1 envelope glycoprotein (Env) trimer. By using biochemical, biophysical and computational methods, we map the previously unknown trimer epitopes of two related antibodies, 3BC315 and 3BC176. A cryo-EM reconstruction of a soluble Env trimer bound to 3BC315 Fab at 9.3 Å resolution reveals that the antibody binds between two gp41 protomers, and neutralizes the virus by accelerating trimer decay. In contrast, bnAb 35O22 binding to a partially overlapping quaternary epitope at the gp120-gp41 interface does not induce decay. A conserved gp41-proximal glycan at N88 was also shown to play a role in the binding kinetics of 3BC176 and 3BC315. Finally, our data suggest that the dynamic structure of the Env trimer influences exposure of bnAb epitopes.

  5. Magnetic anisotropy and chirality of frustrated Cr nanostructures on Au(1 1 1)

    Science.gov (United States)

    Balogh, L.; Udvardi, L.; Szunyogh, L.

    2014-10-01

    By using a fully relativistic embedded cluster Green's function technique we investigated the magnetic anisotropy properties of four different compact Cr trimers (equilateral triangles) and Cr mono-layers deposited on the Au(1 1 1) surface in both fcc and hcp stackings. For all trimers the magnetic ground state was found to be a frustrated 120° Néel configuration. Applying global spin rotations to the magnetic ground state, predictions of an appropriate second order spin Hamiltonian were reproduced with high accuracy by first principles calculations. For the Cr trimers with adjacent Au atoms in similar geometry, we obtained similar values for the in-plane and out-of-plane anisotropy parameters, however, the Dzyaloshinskii-Moriya (DM) interactions appeared to differ remarkably. For two kinds of trimers we found an unconventional magnetic ground state showing 90° in-the-plane rotation with respect to the high symmetry directions. Due to higher symmetry, the in-plane anisotropy term was missing for the mono-layers and distinctly different DM interactions were obtained for the different stackings. The chiral degeneracy of the Néel configurations was lifted by an energy less than 2 meV for the trimers, while this value increased up to about 15 meV per 3 Cr atoms for the hcp packed mono-layer.

  6. An investigation of biodiesel production from microalgae found in Mauritian waters

    Directory of Open Access Journals (Sweden)

    Keshini Beetul

    2014-06-01

    Full Text Available The aim of this study was to assess the lipid content and the subsequent potential of different microalgae present in the Mauritian marine water to produce biodiesel. The share of micro-phytoplankton species in the water column was determined. The cyanobacterial mats and endosymbiotic dinoflagellates were characterised morphologically and genetically using RFLP. The samples were quantified gravimetrically and analysed using 1H &13C NMR spectroscopy. Total micro-phytoplankton count amounted to 6.59±1.27x105 cells L-1which was dominated by diatoms (95.2%, followed by dinoflagellates (2.9% and cyanobacteria (1.9%. The cyanobacterial mats were identified as Leptolyngbya sp. and Nodularia harveyana, and the RFLP characterised the endosymbiotic dinoflagellates as the Symbiodinium clade C. The highest amount of lipid was recorded in the Symbiodinium clade C (38.39±6.58%. 1H and 13C NMR analyses indicated the presence of acyl glycerols. An attempt to synthesise biodiesel by alkaline trans-esterification reaction was also performed and the presence of biodiesel was detected using the Fourier Transform Infrared Spectroscopy. The Infrared analysis yielded peaks at around 1738cm-1 and 1200cm-1 characteristic of the carbonyl and ether groups respectively, indicating the presence of biodiesel.

  7. Low genetic diversity of symbiotic dinoflagellates (Symbiodinium) in scleractinian corals from tropical reefs in southern Hainan Island, China

    Institute of Scientific and Technical Information of China (English)

    Guo-Wei ZHOU; Hui HUANG

    2011-01-01

    Endosymbiotic dinoflagellates in the genus Symbiodinium are among the most abundant and important group of photosynthetic protists found in coral reef ecosystems.In order to further characterize this diversity and compare with other regions of the Pacific,samples from 44 species of scleractinian corals representing 20 genera and 9 families,were collected from tropical reefs in southern Hainan Island,China.Denaturing gradient gel electrophoresis fingerprinting of the ribosomal internal transcribed spacer 2 identified 11 genetically distinct Symbiodinium types that have been reported previously.The majority of reef-building coral species (88.6%) harbored only one subcladal type of symbiont,dominated by host-generalist C1 and C3,and was influenced little by the host’s apparent mode of symbiont acquisition.Some species harbored more than one clade of Symbiodinium (clades C,D) concurrently.Although geographically isolated from the rest of the Pacific,the symbiont diversity in southern Hainan Island was relatively low and similar to both the Great Barrier Reef and Hawaii symbiont assemblages (dominated by clade C Symbiodinium).These results indicate that a specialist symbiont is not a prerequisite for existence in remote and isolated areas,but additional work in other geographic regions is necessary to test this idea.

  8. HIV Subtypes B and C gp120 and Methamphetamine Interaction: Dopaminergic System Implicates Differential Neuronal Toxicity.

    Science.gov (United States)

    Samikkannu, Thangavel; Rao, Kurapati V K; Salam, Abdul Ajees Abdul; Atluri, Venkata S R; Kaftanovskaya, Elena M; Agudelo, Marisela; Perez, Suray; Yoo, Changwon; Raymond, Andrea D; Ding, Hong; Nair, Madhavan P N

    2015-01-01

    HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and substance abuse is known to accelerate HIV disease progression. The HIV-1 envelope protein gp120 plays a major role in binding and budding in the central nervous system (CNS) and impacts dopaminergic functions. However, the mechanisms utilized by HIV-1 clades to exert differential effects and the methamphetamine (METH)-associated dopaminergic dysfunction are poorly understood. We hypothesized that clade B and C gp120 structural sequences, modeling based analysis, dopaminergic effect, and METH potentiate neuronal toxicity in astrocytes. We evaluated the effect of clade B and C gp120 and/or METH on the DRD-2, DAT, CaMKs and CREBP transcription. Both the structural sequence and modeling studies demonstrated that clade B gp120 in V1-V4, α -2 and N-glycosylated sites are distinct from clade C gp120. The distinct structure and sequence variation of clade B gp120 differentially impact DRD-2, DAT, CaMK II and CaMK IV mRNA, protein and intracellular expression compared to clade C gp120. However, CREB transcription is upregulated by both clade B and C gp120, and METH co-treatment potentiated these effects. In conclusion, distinct structural sequences of HIV-1 clade B and C gp120 differentially regulate the dopaminergic pathway and METH potentiates neurotoxicity. PMID:26057350

  9. Molecular phylogeny of Cotesia Cameron, 1891 (Insecta: Hymenoptera: Braconidae: Microgastrinae) parasitoids associated with Melitaeini butterflies (Insecta: Lepidoptera: Nymphalidae: Melitaeini).

    Science.gov (United States)

    Kankare, Maaria; Shaw, Mark R

    2004-07-01

    Phylogenetic relationships among Cotesia Cameron (Braconidae) species parasitising Melitaeini butterflies were examined using DNA sequence data (mitochondrial cytochrome oxidase subunit I and NADH1 dehydrogenase genes, nuclear ribosomal DNA internal transcribed spacer region) as well as 12 microsatellite loci. Molecular data were available from ostensibly six species of Cotesia from 16 host butterfly species in Europe, Asia, and North America. Analysis of the combined sequence data using both maximum parsimony and maximum likelihood revealed two distinct Cotesia clades. In one clade (C. acuminata (Reinhard); C. bignellii (Marshall)) host ranges are apparently narrow and, although Euphydryas (s. lato) is well-utilised, permeation of Melitaea (s. lato) has been slight. In the other clade (C. melitaearum (Wilkinson); C. lycophron (Nixon); C. cynthiae (Nixon)) host utilization across the Melitaeini as a whole is more extensive and the data are consistent with more recent, or active, speciation processes. Neighbour-joining trees calculated separately for the two main clades based on chord distance (DCE) of microsatellite allele frequencies were consistent with phylogenetic trees obtained from the sequence data. Our analysis strongly suggests the presence of several additional, previously unrecognised, Cotesia species parasitising this group of butterflies. PMID:15186808

  10. Diversity of symbiotic algae of the genus Symbiodinium in scleractinian corals of the Xisha Islands in the South China Sea

    Institute of Scientific and Technical Information of China (English)

    Zhi-Jun DONG; Hui HUANG; Liang-Min HUANG; Yuan-Chao LI

    2009-01-01

    Symbiotic algae (Symbiodinium sp.) in scleractinian corals are important in understanding how coral reefs will respond to global climate change. The present paper reports on the diversity of Symbiodinium sp. in 48 scleractinian coral species from 25 genera and 10 families sampled from the Xisha Islands in the South China Sea, which were identified with the use of restriction fragment length polymorphism (RFLP) of the nuclear ribosomal DNA large subunit gene (rDNA). The results showed that: (i) Symbiodinium Clade C was the dominant zooxanthellae in scleractinian corals in the Xisha Islands; (ii) Symbiodinium Clade D was found in the corals Montipora aequituberculata, Galaxea fascicularis, and Plerogyra sinuosa; and (iii) both Symbiodinium Clades C and D were found simultaneously in Montipora digitata, Psammocora contigua, and Galaxeafascicularis. A poor capacity for symbiosis polymorphism, as uncovered by RFLP, in the Xisha Islands indicates that the scleractinian corals have low adaptability to environmental changes. Further studies are needed to investigate zooxanthellae diversity using other molecular markers.

  11. On the modification of the Efimov spectrum in a finite cubic box

    CERN Document Server

    Kreuzer, Simon

    2009-01-01

    Three particles with large scattering length display a universal spectrum of three-body bound states called "Efimov trimers''. We calculate the modification of the Efimov trimers of three identical bosons in a finite cubic box and compute the dependence of their energies on the box size using effective field theory. Previous calculations for positive scattering length that were perturbative in the finite volume energy shift are extended to arbitrarily large shifts and negative scattering lengths. The renormalization of the effective field theory in the finite volume is explicitly verified. Moreover, we investigate the effects of partial wave mixing and study the behavior of shallow trimers near the dimer energy. Finally, we provide numerical evidence for universal scaling of the finite volume corrections.

  12. Efimov studies of an ultracold cloud of 39 K atoms in microgravity: Numerical modelling and experimental design

    Science.gov (United States)

    Mossman, Maren; Engels, Peter; D'Incao, Jose; Jin, Deborah; Cornell, Eric

    2016-05-01

    Ultracold atomic gases at or near quantum degeneracy provide a powerful tool for the investigation of few-body physics. A particularly intriguing few-body phenomenon is the existence of Efimov trimer states at large interatomic scattering lengths. These trimers are predicted to exhibit universal geometric scaling relations, but in practice the situation is complicated e.g. by finite-range and finite-temperature effects. While some Efimov trimers have already been experimentally observed by several groups in ground-based experiments, NASA's Cold Atom Laboratory (CAL) onboard the ISS will greatly enhance the experimentally accessible regimes by providing ultracold clouds of 39 K atoms with temperatures at or below 1 nK, low densities, and long observation times. We present results of numerical modelling and simulations that lay out Efimov experiments capitalizing on the particular strengths of CAL.

  13. Structure of Rotavirus Outer-Layer Protein VP7 Bound with a Neutralizing Fab

    Energy Technology Data Exchange (ETDEWEB)

    Aoki, Scott T.; Settembre, Ethan C.; Trask, Shane D.; Greenberg, Harry B.; Harrison, Stephen C.; Dormitzer, Philip R.; (Stanford-MED); (CH-Boston)

    2009-06-17

    Rotavirus outer-layer protein VP7 is a principal target of protective antibodies. Removal of free calcium ions (Ca{sup 2+}) dissociates VP7 trimers into monomers, releasing VP7 from the virion, and initiates penetration-inducing conformational changes in the other outer-layer protein, VP4. We report the crystal structure at 3.4 angstrom resolution of VP7 bound with the Fab fragment of a neutralizing monoclonal antibody. The Fab binds across the outer surface of the intersubunit contact, which contains two Ca{sup 2+} sites. Mutations that escape neutralization by other antibodies suggest that the same region bears the epitopes of most neutralizing antibodies. The monovalent Fab is sufficient to neutralize infectivity. We propose that neutralizing antibodies against VP7 act by stabilizing the trimer, thereby inhibiting the uncoating trigger for VP4 rearrangement. A disulfide-linked trimer is a potential subunit immunogen.

  14. Immunoadsorber for specific apheresis of autoantibodies in the treatment of bullous pemphigoid.

    Science.gov (United States)

    Mersmann, Michael; Dworschak, Jenny; Ebermann, Kristin; Komorowski, Lars; Schlumberger, Wolfgang; Stöcker, Winfried; Zillikens, Detlef; Probst, Christian; Schmidt, Enno

    2016-01-01

    Bullous pemphigoid (BP) is an autoimmune blistering skin disease associated with autoantibodies against two hemidesmosomal proteins, BP180 (type XVII collagen) and BP230. As the pathogenic relevance of antibodies against the immunodominant NC16A domain of BP180 has been clearly demonstrated, specific removal of these antibodies should be a rational therapeutic approach. Here, we evaluated three recombinant forms of bacterially produced BP180 NC16A, a monomer, trimer, and tetramer, together with different matrices for their efficacy to specifically adsorb autoantibodies from BP plasma samples. An adsorber consisting of NC16A-trimer coupled to NHS-activated Sepharose 4 Fast Flow revealed satisfying adsorption rates and a high specificity. The NC16A-trimer adsorber was regenerable and autoclavable. It has the potential to be used for specific immunoadsorption to treat severe and refractory BP and other pemphigoid diseases associated with BP180 NC16A reactivity. PMID:26498290

  15. Structural basis for membrane anchoring of HIV-1 envelope spike.

    Science.gov (United States)

    Dev, Jyoti; Park, Donghyun; Fu, Qingshan; Chen, Jia; Ha, Heather Jiwon; Ghantous, Fadi; Herrmann, Tobias; Chang, Weiting; Liu, Zhijun; Frey, Gary; Seaman, Michael S; Chen, Bing; Chou, James J

    2016-07-01

    HIV-1 envelope spike (Env) is a type I membrane protein that mediates viral entry. We used nuclear magnetic resonance to determine an atomic structure of the transmembrane (TM) domain of HIV-1 Env reconstituted in bicelles that mimic a lipid bilayer. The TM forms a well-ordered trimer that protects a conserved membrane-embedded arginine. An amino-terminal coiled-coil and a carboxyl-terminal hydrophilic core stabilize the trimer. Individual mutations of conserved residues did not disrupt the TM trimer and minimally affected membrane fusion and infectivity. Major changes in the hydrophilic core, however, altered the antibody sensitivity of Env. These results show how a TM domain anchors, stabilizes, and modulates a viral envelope spike and suggest that its influence on Env conformation is an important consideration for HIV-1 immunogen design. PMID:27338706

  16. Mechanism for pH-dependent gene regulation by amino-terminus-mediated homooligomerization of Bacillus subtilis anti-trp RNA-binding attenuation protein.

    Science.gov (United States)

    Sachleben, Joseph R; McElroy, Craig A; Gollnick, Paul; Foster, Mark P

    2010-08-31

    Anti-TRAP (AT) is a small zinc-binding protein that regulates tryptophan biosynthesis in Bacillus subtilis by binding to tryptophan-bound trp RNA-binding attenuation protein (TRAP), thereby preventing it from binding RNA, and allowing transcription and translation of the trpEDCFBA operon. Crystallographic and sedimentation studies have shown that AT can homooligomerize to form a dodecamer, AT(12), composed of a tetramer of trimers, AT(3). Structural and biochemical studies suggest that only trimeric AT is active for binding to TRAP. Our chromatographic and spectroscopic data revealed that a large fraction of recombinantly overexpressed AT retains the N-formyl group (fAT), presumably due to incomplete N-formyl-methionine processing by peptide deformylase. Hydrodynamic parameters from NMR relaxation and diffusion measurements showed that fAT is exclusively trimeric (AT(3)), while (deformylated) AT exhibits slow exchange between both trimeric and dodecameric forms. We examined this equilibrium using NMR spectroscopy and found that oligomerization of active AT(3) to form inactive AT(12) is linked to protonation of the amino terminus. Global analysis of the pH dependence of the trimer-dodecamer equilibrium revealed a near physiological pK(a) for the N-terminal amine of AT and yielded a pH-dependent oligomerization equilibrium constant. Estimates of excluded volume effects due to molecular crowding suggest the oligomerization equilibrium may be physiologically important. Because deprotonation favors "active" trimeric AT and protonation favors "inactive" dodecameric AT, our findings illuminate a possible mechanism for sensing and responding to changes in cellular pH. PMID:20713740

  17. Analytical Solution of the Bosonic Three-Body Problem

    International Nuclear Information System (INIS)

    We revisit the problem of three identical bosons in free space, which exhibits a universal hierarchy of bound states (Efimov trimers). Modeling a narrow Feshbach resonance within a two-channel description, we map the integral equation for the three-body scattering amplitude to a one-dimensional Schroedinger-type single-particle equation, where an analytical solution of exponential accuracy is obtained. We give exact results for the trimer binding energies, the three-body parameter, the threshold to the three-atom continuum, and the recombination rate

  18. 2,3,4,5-Tetrafluorobenzoic acid–4,4′-bipyridine (2/1

    Directory of Open Access Journals (Sweden)

    Xiaohui Zhu

    2009-08-01

    Full Text Available The asymmetric unit of the title compound, 2C7H2F4O2·C10H8N2, contains one molecule of 2,3,4,5-tetrafluorobenzoic acid (tfb and half of a centrosymmetric 4,4′-bipyridine molecule. Intermolecular O—H...N hydrogen bonds link two tfb molecules and one 4,4′-bipyridine molecule into a trimer. Weak intermolecular C—H...F interactions assemble these trimers into a three-dimensional network structure.

  19. 2,3,4,5-Tetrafluorobenzoic acid–4,4′-bipyridine (2/1)

    OpenAIRE

    Xiaohui Zhu

    2009-01-01

    The asymmetric unit of the title compound, 2C7H2F4O2·C10H8N2, contains one molecule of 2,3,4,5-tetrafluorobenzoic acid (tfb) and half of a centrosymmetric 4,4′-bipyridine molecule. Intermolecular O—H...N hydrogen bonds link two tfb molecules and one 4,4′-bipyridine molecule into a trimer. Weak intermolecular C—H...F interactions assemble these trimers into a three-dimensional network structure.

  20. Structure of the first PDZ domain of human PSD-93

    DEFF Research Database (Denmark)

    Fiorentini, Monica; Nielsen, Ann Kallehauge; Kristensen, Ole;

    2009-01-01

    The crystal structure of the PDZ1 domain of human PSD-93 has been determined to 2.0 A resolution. The PDZ1 domain forms a crystallographic trimer that is also predicted to be stable in solution. The main contributions to the stabilization of the trimer seem to arise from interactions involving the...... well as of the closely related human PSD-95 PDZ1 shows that they are very similar in terms of amino-acid composition. However, the cleft is significantly narrower in PSD-95. This could be part of the basis of peptide selectivity between PSD-93 PDZ1 and PSD-95 PDZ1....

  1. Investigation into chromophore excited-state coupling in allophycocyanin

    Science.gov (United States)

    Zheng, Xiguang; Zhao, Fuli; Wang, He Z.; Gao, Zhaolan; Yu, Zhenxin; Zhu, Jinchang; Xia, Andong; Jiang, Lijin

    1994-08-01

    Both theoretical and experimental studies are presented on chromophore excited-state coupling in linker-free allophycocyanin (APC), one of the antenna phycobiliproteins in algal photosynthesis. A three-site-coupling model has been introduced to describe the exciton interaction mechanism amoung the excited (beta) chromophore in APC, and the exciton energy splitting is estimated. Picosecond polarized fluorescence experiments both on monomeric and trimeric APC isolated from alga Spirulina platensis have been performed. The experimental results show that APC monomer and trimer exhibit remarkedly different spectropic characteristics, and satisfy the suggestion of strong excited- state coupling among chromophores in APC.

  2. Mitochondrial Carnitine Palmitoyltransferase 1a (CPT1a) Is Part of an Outer Membrane Fatty Acid Transfer Complex*

    OpenAIRE

    Lee, Kwangwon; Kerner, Janos; Hoppel, Charles L.

    2011-01-01

    CPT1a (carnitine palmitoyltransferase 1a) in the liver mitochondrial outer membrane (MOM) catalyzes the primary regulated step in overall mitochondrial fatty acid oxidation. It has been suggested that the fundamental unit of CPT1a exists as a trimer, which, under native conditions, could form a dimer of the trimers, creating a hexamer channel for acylcarnitine translocation. To examine the state of CPT1a in the MOM, we employed a combined approach of sizing by mass and isolation using an immu...

  3. Effect of trapping on transport coherence III: Dissipation in the stochastic Liouville equation approach

    International Nuclear Information System (INIS)

    We used the formal stochastic Liouville equations within Haken-Strobl-Reineker parametrization for the description of the influence of the bath on the memory functions entering the GME for a dimer and a linear trimer with a trap (here modeled as a sink). The often used inclusion of the noncoherent regime in the MF by an exponentially damped prefactor (after Kenkre's prescription) does not hold for finite systems. The analytical form of the MF is changed more pronouncely and the influence of the sink in the center of the trimer runs parallel with the influence of the bath in destroying the coherence. (author). 60 refs

  4. Role of Solvent, pH, and Molecular Size in Excited-State Deactivation of Key Eumelanin Building Blocks: Implications for Melanin Pigment Photostability

    DEFF Research Database (Denmark)

    Gauden, M.; Pezzella, A.; Panzella, L.;

    2008-01-01

      Ultrafast time-resolved fluorescence spectroscopy has been used to investigate the excited state dynamics of the basic eumelanin building block 5,6-dihydroxyindole-2-carboxylic acid  (DHICA) its acetylated, methylated and carboxylic ester derivatives as well as two oligomers, a dimer and a trimer...... in the O-acetylated forms. The results show that: 1) excited state decays are faster for the trimer relative to the monomer; 2) for parent DHICA, excited state lifetimes are much shorter in aqueous acidic medium (380 ps) as compared to organic solvent (acetonitrile, 2.6 ns); 3) variation of...

  5. Positional Scanning Synthesis of a Peptoid Library Yields New Inducers of Apoptosis that Target Karyopherins and Tubulin.

    Science.gov (United States)

    Vendrell-Navarro, Glòria; Rúa, Federico; Bujons, Jordi; Brockmeyer, Andreas; Janning, Petra; Ziegler, Slava; Messeguer, Angel; Waldmann, Herbert

    2015-07-27

    We describe the synthesis of a library of 11, 638 N-alkylglycine peptoid trimers in a positional scanning format with adjustment of reaction conditions to account for different reactivities of the monomer building blocks. Evaluation of the library by high-content phenotypic screening for modulators of the cytoskeleton and mitosis resulted in the identification of two apoptosis-inducing peptoids, which, despite their structural similarity, target different proteins and cellular mechanisms. Whereas one peptoid binds to karyopherins, which mediate nuclear transport, the other N-alkylglycine trimer binds tubulin at the vinca alkaloid binding site. PMID:26010161

  6. A transient absorption study of allophycocyanin

    Indian Academy of Sciences (India)

    Y J Shiu; J M Zhang; M Hayashi; V Gulbinas; C M Yang; S H Lin

    2002-12-01

    Transient dynamics of allophycocyanin trimers and monomers are observed by using the pump-probe, transient absorption technique. The origin of spectral components of the transient absorption spectra is discussed in terms of both kinetics and spectroscopy. We find that the energy gap between the ground and excited states of the unexcited subunit of allophycocyanin monomer decreases via an interaction with another excited subunit. For allophycocyanin trimer, we find that the fast dynamics results from the fast internal conversion and the first excited state is the only one electronic state which can trap the final population.

  7. Glycolonitrile oligomerization: structure of isolated oxazolines, potential heterocycles on the early earth

    Science.gov (United States)

    Arrhenius, G.; Baldridge, K. K.; Richards-Gross, S.; Siegel, J. S.; Bada, J. L. (Principal Investigator)

    1997-01-01

    A study of glycolonitrile polymerization has led to the isolation and characterization of two 2,5-dihydro-4-aminooxazoles, 4 and 5. Previous reports have misassigned these structures as s-triazines or pyrimidines. X-ray diffraction analysis of crystals of 4 and an acetylated oxazole derivative of 5 (6) confirm the proposed structures. Ab initio computations are used to assess the relative thermodynamic stability of three trimer isomers (an s-triazine, an aminohydroxypyrimidine, and an aminooxazoline), and the results indicate that 4 is a novel kinetic product. Mechanistic considerations rationalize kinetic oxazole formation over the more customary triazine or pyrimidine trimers.

  8. Large negative differential resistance and rectifying performance modulated by contact sites in fused thiophene trimmer-based molecular devices

    International Nuclear Information System (INIS)

    By applying density functional theory with non-equilibrium Green's function formalism, we have carried out a theoretical study of the electron transport in fused thiophene trimmer-based molecular devices with ethylene connections at three different sites. The simulation results indicate that the electronic transport properties strongly depend on the contact sites. Negative differential resistance and rectifying behaviors occur simultaneously in the current–voltage curves when ethylene connects the fused thiophene trimer at one second-nearest site and one third-nearest site. A larger negative differential resistance occurs only when ethylene connects the fused thiophene trimer at two second-nearest sites.

  9. Crystallization and molecular-replacement solution of a truncated form of human recombinant tetranectin

    DEFF Research Database (Denmark)

    Nielsen, Betina Bryde; Kastrup, Jette Sandholm Jensen; Rasmussen, Hanne B.; Graversen, J H; Etzerodt, Michael; Thøgersen, Hans Christian; Larsen, Ingrid K.

    The two C-terminal domains, TN23 (residues 17-181), of human recombinant tetranectin, a plasminogen kringle 4 binding C-type lectin, have been crystallized in two different space groups. Using PEG 8000 as precipitant and at a pH of 8.5, crystals belonging to the monoclinic space group C2 are obta...... has been collected from the monoclinic crystals. Using the structure of full-length tetranectin, a molecular-replacement solution has been obtained. The crystal packing shows that TN23 crystallizes as a trimer, with one trimer in the asymmetric unit....

  10. Optical spectroscopy on size selected gold clusters deposited in rare gas matrices

    International Nuclear Information System (INIS)

    We report on the successful 'soft-landing' of size selected Au trimers in solid Krypton matrices. The Au cations are produced by sputtering, mass-selected in a quadrupole mass spectrometer, co-deposited with Krypton on a cooled CaF2 substrate, and neutralized by low energy electrons. The deposition of low kinetic energy cations (10 eV) gives rise to strong excitation bands, detected by the emitted fluorescence light, which are unambiguously attributed to Au trimers. The deposition and fragmentation process is qualitatively discussed. (orig.)

  11. A mechanism of protein-mediated fusion: coupling between refolding of the influenza hemagglutinin and lipid rearrangements.

    OpenAIRE

    Kozlov, M M; Chernomordik, L V

    1998-01-01

    Although membrane fusion mediated by influenza virus hemagglutinin (HA) is the best characterized example of ubiquitous protein-mediated fusion, it is still not known how the low-pH-induced refolding of HA trimers causes fusion. This refolding involves 1) repositioning of the hydrophobic N-terminal sequence of the HA2 subunit of HA ("fusion peptide"), and 2) the recruitment of additional residues to the alpha-helical coiled coil of a rigid central rod of the trimer. We propose here a mechanis...

  12. Assembly of spikes into coronavirus particles is mediated by the carboxy-terminal domain of the spike protein

    NARCIS (Netherlands)

    Godeke, G J; de Haan, C A; Rossen, J W; Vennema, H; Rottier, P J

    2000-01-01

    The type I glycoprotein S of coronavirus, trimers of which constitute the typical viral spikes, is assembled into virions through noncovalent interactions with the M protein. Here we demonstrate that incorporation is mediated by the short carboxy-terminal segment comprising the transmembrane and end

  13. Development and validation of analytical methods for monomeric and oligomeric migrants from nylon 12 packaging materials.

    NARCIS (Netherlands)

    Stoffers, N.H.; Brandl, F.; Linssen, J.P.H.; Franz, R.

    2003-01-01

    Analytical methods for the determination of laurolactam-the monomer of nylon 12-as well as the cyclic dimer and trimer were established. High performance liquid chromatography using ultraviolet (HPLC-UV) and mass spectrometric detection (HPLC-MS) were both found suitable to identify and quantify mon

  14. Structural characterization of human and bovine lung surfactant protein D

    DEFF Research Database (Denmark)

    Leth-Larsen, Rikke; Holmskov, U; Højrup, P

    1999-01-01

    Human and bovine surfactant proteins D (SP-D) were purified from late amniotic fluid and bronchioalveolar lavage on the basis of its Ca(2+)-dependent affinity for maltose. The molecular mass of a trimeric subunit was determined by matrix-assisted laser desorption ionization MS to lie in the range...

  15. Intramolecular Interactions in Novel Macrocyclic Materials

    Science.gov (United States)

    Goodson, Theodore

    2009-03-01

    In this presentation I will report a strongly interacting new dendrimer system with an extended spectroscopic unit (coherent domain) beyond the trimer configuration. Strong cooperative enhancement of two-photon absorption cross-section was observed when going from the trimer arrangement to the next generation. Combination of a variety of femtosecond spectroscopy methods such as femtosecond time-resolved fluorescence upconversion, transient absorption, transient grating, three pulse photon echo peak shift experiments complemented with those of steady state spectroscopy allowed us to compare the properties of absorption states with those of fluorescence states, to estimate the reorganization energies, and the extent of inhomogeneous broadening. Our measurements indicated that spectroscopic unit (domain) is different for the trimer system and for the dendrimers of higher generation numbers. This coherent domain extends over the trimer geometry and its size is comparable with the size of the dendrimer G1 comprising nine linear segments. We have also investigated the novel applications of a two-dimensional carbon network structure's building blocks. The material shows very interesting two-photon absorption properties as well as strongly coupled optical excitations. They have also been suggested as good building blocks for molecular electronics applications.

  16. Effect of treatment with human apolipoprotein A-I on atherosclerosis in uremic apolipoprotein-E deficient mice

    DEFF Research Database (Denmark)

    Pedersen, Tanja Xenia; Bro, Susanne; Andersen, Mikkel H;

    2009-01-01

    OBJECTIVE: Uremia markedly increases the risk of atherosclerosis. Thus, effective anti-atherogenic treatments are needed for uremic patients. This study examined effects of non-lipidated recombinant human apoA-I (h-apoA-I) and a recombinant trimeric apoA-I molecule (TripA-I) on lipid metabolism a...

  17. Main: 1UCX [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1UCX 大豆 Soybean Glycine max (L.) Merrill Glycinin G1 Precursor [Contains: Glycinin A1a Subunit ... Soybean Proglycinin Mutants C12g And C88s. J.Agric.Food ... Chem; V. 51 4633 2003 Proglycinin, Soybean, Trimer ...

  18. Main: 1UD1 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1UD1 大豆 Soybean Glycine max (L.) Merrill Glycinin G1 Precursor [Contains: Glycinin A1a Subunit ... Soybean Proglycinin Mutants C12g And C88s. J.Agric.Food ... Chem; V. 51 4633 2003 Glycinin, Soybean, Trimer SW ...

  19. Comparative Structural and Computational Analysis Supports Eighteen Cellulose Synthases in the Plant Cellulose Synthesis Complex.

    Science.gov (United States)

    Nixon, B Tracy; Mansouri, Katayoun; Singh, Abhishek; Du, Juan; Davis, Jonathan K; Lee, Jung-Goo; Slabaugh, Erin; Vandavasi, Venu Gopal; O'Neill, Hugh; Roberts, Eric M; Roberts, Alison W; Yingling, Yaroslava G; Haigler, Candace H

    2016-01-01

    A six-lobed membrane spanning cellulose synthesis complex (CSC) containing multiple cellulose synthase (CESA) glycosyltransferases mediates cellulose microfibril formation. The number of CESAs in the CSC has been debated for decades in light of changing estimates of the diameter of the smallest microfibril formed from the β-1,4 glucan chains synthesized by one CSC. We obtained more direct evidence through generating improved transmission electron microscopy (TEM) images and image averages of the rosette-type CSC, revealing the frequent triangularity and average cross-sectional area in the plasma membrane of its individual lobes. Trimeric oligomers of two alternative CESA computational models corresponded well with individual lobe geometry. A six-fold assembly of the trimeric computational oligomer had the lowest potential energy per monomer and was consistent with rosette CSC morphology. Negative stain TEM and image averaging showed the triangularity of a recombinant CESA cytosolic domain, consistent with previous modeling of its trimeric nature from small angle scattering (SAXS) data. Six trimeric SAXS models nearly filled the space below an average FF-TEM image of the rosette CSC. In summary, the multifaceted data support a rosette CSC with 18 CESAs that mediates the synthesis of a fundamental microfibril composed of 18 glucan chains. PMID:27345599

  20. Gclust Server: 29094 [Gclust Server

    Lifescience Database Archive (English)

    Full Text Available hock transcription factor, activates multiple genes in response to hyperthermia 3 1.00e-60 0.0 0.0 0.0 0.0 0...ive annotation Trimeric heat shock transcription factor, activates multiple genes in response to hyperthermia

  1. Preparation of the individual diastereomers of adenylyl-(2'-5')-P-thioadenylyl-(2'-5')-adenosine and their 5'-phosphorylated derivatives.

    Science.gov (United States)

    de Vroom, E; Fidder, A; Saris, C P; van der Marel, G A; van Boom, J H

    1987-01-01

    The individual diastereomers of trimer A2'p5'A2'p(s)5'A, containing one phosphorothioate linkage, were prepared via a modified hydroxybenzotriazole phosphotriester approach. The 5'-phosphorylated derivatives of the latter compounds were obtained after phosphorylation with a 6-trifluoromethyl-1-benzotriazolyl activated phosphoromorpholidate. PMID:3697086

  2. Cyclotrimerization of nitriles catalyzed by Li3N

    Institute of Scientific and Technical Information of China (English)

    DENG Zhaoxiang; QIU Wenfeng; LI Weijia; LI Yadong

    2004-01-01

    Nitriles were unexpectedly trimerized into s-triazines or amino-pyrimidines in high yields in the presence of catalytic amount of Li3N, resulting in a simple, solvent-free and easy-to-scale-up one-pot way to synthesize s-triazines and 4-amino-pyrimidines with high yield.

  3. 21 CFR 177.2470 - Polyoxymethylene copolymer.

    Science.gov (United States)

    2010-04-01

    ...-ylene copolymer can be identified by its characteristic infrared spectrum. (2) Minimum number average molecular weight of the copolymer is 15,000 as determined by a method titled “Number Average Molecular... product of trioxane (cyclic trimer of formaldehyde) and a maximum of 5 percent by weight of...

  4. Converging signals synergistically activate the LAMC2 promoter and lead to accumulation of the laminin gamma 2 chain in human colon carcinoma cells

    DEFF Research Database (Denmark)

    Olsen, Jørgen; Kirkeby, Lene T; Brorsson, Marianne M; Dabelsteen, Sally; Troelsen, Jesper T; Bordoy, Randi; Fenger, Kirsten; Larsson, Lars-Inge; Simon-Assmann, Patricia

    The trimeric extracellular matrix molecule laminin-5 and its constituent chains (alpha 3, beta 3, gamma 2) are normally not detectable intracellularly in intestinal epithelial cells but the laminin gamma 2 chain can be detected in cancer cells at the invasive front of a subset of colon carcinomas...

  5. Structures of dCTP deaminase from Escherichia coli with bound substrate and product: reaction mechanism and determinants of mono- and bifunctionality for a family of enzymes

    DEFF Research Database (Denmark)

    Johansson, Eva; Fanø, Mathias; Bynck, Julie H;

    2005-01-01

    complex with dUTP and Mg(2+), and the mutant enzyme also with the substrate dCTP and Mg(2+). The enzyme is a third member of the family of the structurally related trimeric dUTPases and the bifunctional dCTP deaminase-dUTPase from Methanocaldococcus jannaschii. However, the C-terminal fold is completely...

  6. Ionic liquids from Car-Parrinello simulations, part I: liquid AlCl3.

    Science.gov (United States)

    Kirchner, Barbara; Seitsonen, Ari P; Hutter, Jürg

    2006-06-15

    The properties of isolated AlCl3 clusters and the bulk system are investigated by means of static and dynamic electronic structure methods. We find important structural motifs with the edge connectivity dominant in a dimer and the corner connectivity dominant in a trimer. Furthermore, the trimer cluster exhibits an interesting ring structure with large cooperative effects relative to the dimer. Comparing the found structural motifs in isolated molecule calculations with the structure of the liquid allows us to determine the dominance of edge connectivity in the liquid. The size of the clusters present in the liquid indicates indeed that the dimer is the most abundant species, but there are also trimers, tetramers, and pentamers present. From the local dipole analysis both for the isolated clusters as well as for the liquid, further proof for the edge connectivity is given. However, all results point to the fact that there is also some small percentage of corner connectivity present that might be attributed to the most stable corner-connected cluster, namely the trimer. Importantly, we find that energetic considerations of isolated (static) clusters only do not represent the findings in liquid phase. Instead, a quantum cluster equilibrium approach or simulations are needed. PMID:16771422

  7. (S,S)-Lactoyllactic acid and (S,S,S)-lactoyllactoyllactic acid

    NARCIS (Netherlands)

    Lutz, M.; Van Krieken, J.

    2010-01-01

    The dimeric condensation product of lactic acid, namely (S,S)-2-[(2-hydroxypropanoyl)oxy]propanoic acid, C(6)H(10)O(5), (I), crystallizes with two independent molecules in the asymmetric unit, which both have an essentially planar backbone. The trimeric condensation product, namely (S,S,S)-3-hydroxy

  8. Fluorescence correlation spectroscopy to study antibody binding and stoichiometry of complexes

    Science.gov (United States)

    Swift, Kerry M.; Matayoshi, Edmund D.

    2008-02-01

    FCS (fluorescence correlation spectroscopy) was used to study the association at the single molecule level of tumor necrosis factor alpha (TNF-α) and two of its protein antagonists Humira (TM) (adalimumab), a fully humanized monoclonal antibody, and Enbrel (TM) (etanercept), a soluble form of the TNF receptor. Single molecule approaches potentially have the advantage not only of enhanced sensitivity, but also of observing at equilibrium the details that would otherwise be lost in classical ensemble experiments where heterogeneity is averaged. We prepared fluorescent conjugates of the protein drugs and their biological target, the trimeric soluble form of TNF-α. The bivalency of adalimumab and the trimeric nature of TNF-α potentially allow several forms of associative complexes that may differ in stoichiometry. Detailed knowledge of this reaction may be relevant to understanding adalimumab's pharmacological properties. Our FCS data showed that a single trimeric TNF-α can bind up to three adalimumab molecules. Under some conditions even larger complexes are formed, apparently the result of cross-linking of TNF-α trimers by adalimumab. In addition, distinct differences between Humira and Enbrel were observed in their association with TNF-α.

  9. Use of Cyclic Di- and Triperoxides as Initiators of Styrene Polymerization at High Temperature with a View to Their Use in Industrial Applications

    OpenAIRE

    A. I. Cañizo; Cerna, J. R.; Eyler, G. N.; Morales, G.

    2000-01-01

    In industry, the bulk free radical polymerization of styrene takes place with the aid of peroxide initiators such as benzoyl peroxide. In this work di- and trimeric cyclic peroxides were used as initiators of the styrene polymerization in order to increase the rate of polymerization and molecular weights simultaneously.

  10. Hydrogen bonding in polyanilines

    Energy Technology Data Exchange (ETDEWEB)

    Bahceci, S. (Department of Chemistry, Middle East Technical University, Ankara 06531 (Turkey)); Toppare, L. (Department of Chemistry, Middle East Technical University, Ankara 06531 (Turkey)); Yurtsever, E. (Department of Chemistry, Middle East Technical University, Ankara 06531 (Turkey))

    1994-11-29

    Hydrogen bonding between poly(bisphenol A carbonate) (PC) and polyaniline (PAn) is analyzed using semi-empirical quantum methodology. Fully optimized AM1 molecular orbital calculations are reported for various aniline structures (monomer, dimer and trimer), the monomer of the PC and the hydrogen-bonded model of PAn-PC oligomer. ((orig.))

  11. Dsl1p, Tip20p, and the novel Dsl3(Sec39) protein are required for the stability of the Q/t-SNARE complex at the endoplasmic reticulum in yeast

    DEFF Research Database (Denmark)

    Kraynack, Bryan A; Chan, Angela; Rosenthal, Eva Helga;

    2005-01-01

    Golgi-ER retrograde transport. Size exclusion chromatography and affinity purification approaches confirmed that Dsl3p is associated with subunits of the "Dsl1p complex." The complex also includes the Q/t-SNARE proteins, Use1p, Sec20p, and Ufe1p, integral membrane proteins that constitute the trimeric...

  12. Momentum-space calculation of four-boson recombination

    OpenAIRE

    Deltuva, A.

    2012-01-01

    The system of four identical bosons with large two-boson scattering length is described using momentum-space integral equations for the four-particle transition operators. The creation of Efimov trimers via ultracold four-boson recombination is studied. The universal behavior of the recombination rate is demonstrated.

  13. Modulating TRAP-mediated transcription termination by AT during transcription of the leader region of the Bacillus subtilis trp operon.

    Science.gov (United States)

    Sharma, Shraddha; Gollnick, Paul

    2014-05-01

    An 11-subunit protein called trp RNA binding Attenuation Protein (TRAP) controls attenuation of the tryptophan biosynthetic (trpEDCFBA) operon in Bacillus subtilis. Tryptophan-activated TRAP binds to 11 (G/U)AG repeats in the 5' leader region of trp mRNAs, and downregulates expression of the operon by promoting transcription termination prior to the structural genes. Anti-TRAP (AT) is an antagonist that binds to tryptophan-activated TRAP and prevents TRAP from binding to RNA, thereby upregulating expression of the trp genes. AT forms trimers, and multiple trimers bind to a TRAP 11mer. It is not known how many trimers must bind to TRAP in order to interfere with RNA binding. Studies of isolated TRAP and AT showed that AT can prevent TRAP from binding to the trp leader RNA but cannot dissociate a pre-formed TRAP-RNA complex. Here, we show that AT can prevent TRAP-mediated termination of transcription by inducing dissociation of TRAP from the nascent RNA when it has bound to fewer than all 11 (G/U)AG repeats. The 5'-most region of the TRAP binding site in the nascent transcript is most susceptible to dissociation from TRAP. We also show that one AT trimer bound to TRAP 11mer reduces the affinity of TRAP for RNA and eliminates TRAP-mediated transcription termination in vitro. PMID:24682818

  14. The chicken erythrocyte-specific MHC antigen. Characterization and purification of the B-G antigen by monoclonal antibodies

    DEFF Research Database (Denmark)

    Salomonsen, J; Skjødt, K; Crone, M;

    1987-01-01

    ), when labeled erythrocytes were the antigen source, or trimers (130 kd), when B-G was purified and precipitated from CEM. The B-G antigen was unglycosylated as studied by in vitro synthesis in the presence or absence of tunicamycin, binding experiments with lectin from Phaseolus limensis, and treatment...

  15. Early stages of amyloid fibril formation studied by liquid-state NMR: the peptide hormone glucagon

    DEFF Research Database (Denmark)

    Svane, Anna Sigrid Pii; Jahn, Kasper; Deva, Taru; Malmendal, Anders; Otzen, Daniel; Dittmer, Jens; Nielsen, Niels Chr

    2008-01-01

    the course of the fibril formation process. Kinetic information is extracted from the time course of the residual free glucagon signal decay. This suggests that glucagon amyloids form by a nucleated growth mechanism in which trimers (rather than monomers) of glucagon interact directly with the growing...

  16. 1-Hexyne Cyclotrimerization Catalyzed by Cyclopentadienyl Rhodium(I) Complexes

    Czech Academy of Sciences Publication Activity Database

    Auerová, Kateřina; Čermák, Jan; Blechta, Vratislav; Kvíčala, J.

    Tarragona: Ind. Gráf. Gabriel Gibert, 2002. s. 310. [International Symposium on Homogeneous Catalysis /13./. 03.09.2002-07.09.2002, Tarragona] R&D Projects: GA AV ČR IAA4072203 Keywords : trimerization * rhodium catalysts * cyclopentadienyl complexes Subject RIV: CC - Organic Chemistry

  17. Crystal structure analysis of a glycosides hydrolase family 42 cold-adapted ß-galactosidase from Rahnella sp. R3

    Science.gov (United States)

    The ß-galactosidase isolated from a psychrotrophic bacterium, Rahnella sp. R3 (R-ß-Gal), exhibits high activity at low temperature. R-ß-Gal is a member of the glycoside hydrolases family 42 (GH42), and forms a 225 kDa trimeric structure in solution. The X-ray crystal structure of R-ß-Gal was determi...

  18. Localization of Temperature Using Plasmonic Hot Spots in Metal Nanostructures: The Nano-Optical Antenna Approach and Fano Effect

    CERN Document Server

    Khorashad, Larousse Khosravi; Valentine, Jason; Govorov, Alexander O

    2016-01-01

    It is challenging to strongly localize temperature in small volumes because heat transfer is a diffusive process. Here we show how to overcome this limitation using electrodynamic hot spots and interference effects in the regime of continuous-wave (CW) excitation. We introduce a set of figures of merit for the localization of temperature and for the efficiency of the plasmonic photo-thermal effect. Our calculations show that the temperature localization in a trimer nanoparticle assembly is a complex function of the geometry and sizes. Large nanoparticles in the trimer play the role of the nano-optical antenna whereas the small nanoparticle in the plasmonic hot spot acts as a nano-heater. Under the peculiar conditions, the temperature increase inside a nanoparticle trimer can be localized in a hot spot region at the small heater nanoparticle and, in this way, a thermal hot spot can be realized. However, the overall power efficiency of temperature generation in this trimer is much smaller than that of a single ...

  19. Serum amyloid P component inhibits influenza A virus infections: in vitro and in vivo studies

    DEFF Research Database (Denmark)

    Horvath, A; Andersen, I; Junker, K;

    2001-01-01

    showed that SAP bound to HA trimers, monomers and HA1 and HA2 subunits of influenza A virus. Binding studies indicated that galactose, mannose and fucose moieties contributed to the SAP reacting site(s). Intranasal administration of human SAP to mice induced no demonstrable toxic reactions, and...

  20. Isothermal Titration Calorimetry and Macromolecular Visualization for the Interaction of Lysozyme and Its Inhibitors

    Science.gov (United States)

    Wei, Chin-Chuan; Jensen, Drake; Boyle, Tiffany; O'Brien, Leah C.; De Meo, Cristina; Shabestary, Nahid; Eder, Douglas J.

    2015-01-01

    To provide a research-like experience to upper-division undergraduate students in a biochemistry teaching laboratory, isothermal titration calorimetry (ITC) is employed to determine the binding constants of lysozyme and its inhibitors, N-acetyl glucosamine trimer (NAG[subscript 3]) and monomer (NAG). The extremely weak binding of lysozyme/NAG is…

  1. Au/si(111): Analysis of the (#sq root#3X#sq root#3)R 30 deg and 6X6 structures by in-plane x-ray diffraction

    DEFF Research Database (Denmark)

    Dornisch, D.; Moritz, W.; Schulz, H.; Feidenhans'l, R.; Nielsen, M.; Grey, F.; Johnson, R.L.

    1991-01-01

    In-plane, fractional-order diffraction-data sets from thin Au layers on Si(111) with (square-root 3 X square-root 3)R 30-degrees and 6 X 6 structures were measured at the wiggler beamline W1 at the Hamburg synchrotron radiation laboratory. For the square-root 3 X square-root 3 structure the trimer...... model is confirmed with an Au-Au distance of 2.8 angstrom. In the square-root 3 X square-root 3 unit cell, two additional sites beside the Au trimer were found which can be identified with distorted substrate layers or additional partially occupied Au sites. The 6 X 6 structure is a sixfold twinned...... structure. The observed Patterson function clearly indicates the main features of the structural units. Each consists of three trimer clusters of Au atoms, forming a nearly equilateral triangle. The local structure of each trimer is either the original square-root 3 X square-root 3 structure or a twin...

  2. Ammonium recruitment and ammonia transport by E. coli ammonia channel AmtB

    DEFF Research Database (Denmark)

    Nygaard, Thomas Pedersen; Rovira, C.; Peters, Günther H.j.; Jensen, M.Ø.

    2006-01-01

    To investigate substrate recruitment and transport across the Escherichia coli Ammonia transporter B (AmtB) protein, we performed molecular dynamics simulations of the AmtB trimer. We have identified residues important in recruitment of ammonium and intraluminal binding sites selective of ammoniu...

  3. Rapid Multistep Synthesis of a Bioactive Peptidomimetic Oligomer for the Undergraduate Laboratory

    Science.gov (United States)

    Utku, Yeliz; Rohatgi, Abhinav; Yoo, Barney; Kirshenbaum, Kent; Zuckermann, Ronald N.; Pohl, Nicola L.

    2010-01-01

    Peptidomimetic compounds are increasingly important in drug-discovery applications. We introduce the synthesis of an N-substituted glycine oligomer, a bioactive "peptoid" trimer. The six-step protocol is conducted on solid-phase resin, enabling the synthesis to be performed by undergraduate organic chemistry students. This synthesis lab was…

  4. Calorimetric and spectroscopic investigations of the thermal denaturation of wild type nitrite reductase

    NARCIS (Netherlands)

    Stirpe, A; Guzzi, R; Wijma, H; Verbeet, MP; Canters, GW; Sportelli, L

    2005-01-01

    Nitrite reductase (NiR) is a multicopper protein, with a trimeric structure containing two types of copper site: type I is present in each subunit whereas type 2 is localized at the subunits interface. The paper reports on the thermal behaviour of wild type NiR from Alcaligenes faecalis S-6. The tem

  5. Highly efficient antibody immobilization with multimeric protein Gs coupled magnetic silica nanoparticles

    Science.gov (United States)

    Lee, J. H.; Choi, H. K.; Chang, J. H.

    2011-10-01

    This work reports the immobilization of monomeric, dimeric and trimer protein Gs onto silica magnetic nanoparticles for self-oriented antibody immobilization. To achieve this, we initially prepared the silica-coated magnetic nanoparticle having about 170 nm diameters. The surface of the silica coated magnetic nanoparticles was modified with 3- aminopropyl-trimethoxysilane (APTMS) to chemically link to multimeric protein Gs. The conjugation of amino groups on the SiO2-MNPs to cysteine tagged in multimeric protein Gs was performed using a sulfo-SMCC coupling procedure. The binding efficiencies of monomer, dimer and trimer were 77 %, 67 % and 55 % respectively. However, the efficiencies of antibody immobilization were 70 %, 83 % and 95 % for monomeric, dimeric and trimeric protein G, respectively. To prove the enhancement of accessibility by using multimeric protein G, FITC labeled goat-anti-mouse IgG was treated to mouse IgG immobilized magnetic silica nanoparticles through multimeric protein G. FITC labeled goat anti-mouse IgGs were more easily bound to mouse IgG immobilized by trimeric protein G than others. Finally protein G bound silica magnetic nanoparticles were utilized to develop highly sensitive immunoassay to detect hepatitis B antigen.

  6. Human immunodeficiency virus type 1 specific cytotoxic T lymphocyte responses in Chinese infected with HIV-1 B'/C Recombinant (CRF07_BC

    Directory of Open Access Journals (Sweden)

    Yu Xu G

    2007-08-01

    Full Text Available Abstract Background The characterization of HIV-1-specific T cell responses in people infected with locally circulating HIV-1 strain will facilitate the development of HIV-1 vaccine. Sixty intravenous drug users infected with HIV-1 circulating recombinant form 07_BC (CRF07_BC, which has been spreading rapidly in western China from north to south, were recruited from Xinjiang, China to assess the HIV-1-specific T cell responses at single peptide level with overlapping peptides (OLP covering the whole concensus clades B and C proteome. Results The median of the total magnitude and total number of OLPs recognized by CTL responses were 10925 SFC/million PBMC and 25 OLPs, respectively, when tested by clade C peptides, which was significantly higher than when tested by clade B peptides. The immunodominant regions, which cover 14% (58/413 of the HIV-1 proteome, are widely distributed throughout the HIV-1 proteome except in Tat, Vpu and Pol-PR, with Gag, Pol-RT, Pol-Int and Nef being most frequently targeted. The subdominant epitopes are mostly located in p24, Nef, integrase, Vpr and Vif. Of the responses directed to clade C OLPs, 61.75% (972/1574 can be observed when tested with corresponding clade B OLPs. However, Pol-PR and Vpu tend to be targeted in the clade B sequence rather than the clade C sequence, which is in line with the recombinant pattern of CRF07_BC. Stronger and broader CTL responses in subjects with CD4 cell counts ranging from 200 to 400/mm3 were observed when compared to those with less than 200/mm3 or more than 400/mm3, though there have been no significant correlations identified between the accumulative CTL responses or overall breadth and CD4 cell count or plasma viral load. Conclusion This is the first study conducted to comprehensively address T cell responses in Chinese subjects infected with HIV-1 CRF07_BC in which subtle differences in cross-reactivity were observed, though similar patterns of overall immune responses were

  7. Ecology and phylogeny of birds foraging at outdoor restaurants in Sweden

    Science.gov (United States)

    Sjöstedt de Luna, Sara; Blank, Henrick; Lundqvist, Henrik

    2015-01-01

    Abstract Background Birds frequently visit the outdoor serving areas of restaurants to feed on scraps of food and leftovers. Although this feeding association between humans and birds is widespread and could have significant effects, both positive and negative, for all taxa involved, the authors know of no published studies that have investigated restaurant bird communities. To lay the foundation for future research, the authors conducted a basic study of birds at 80 outdoor restaurants in Sweden, identifying which species and taxonomic clades of birds visited the restaurants and comparing restaurant birds in urban and rural environments. New information Thirteen species of birds visited the outdoor restaurants. Eight of these species were predominant, i.e. accounting for 51% or more of bird presence (sum of minutes of all individual birds) at one or more restaurants. Every restaurant studied had a predominant species, but species often differed from each other in frequency of predominance in different landscapes. No endangered species were seen visiting restaurants. However, three farmland bird species (House Sparrow Passer domesticus, White Wagtail Motacilla alba, Eurasian Tree Sparrow Passer montanus), whose numbers are reported to be declining in the countryside, were predominant at the majority of restaurants in rural areas, suggesting that rural restaurants might be able to contribute to the conservation of these species. The thirteen species of restaurant-visiting birds belonged to five monophyletic clades. Ninety percent of all restaurants had, as their predominant species, birds from either Clade A (Passeridae, Motacillidae, Fringillidae) or Clade C (Corvidae). Statistical testing revealed that Clade A and Clade C were distributed differently in environments along the urban-rural gradient. At all spatial scales measured, birds of Clade C were predominant at the majority of restaurants in urban areas, while birds of Clade A were the predominant clade at the

  8. Many-body forces and stability of the alkaline-earth tetramers

    International Nuclear Information System (INIS)

    Graphical abstract: Many-body forces effect. In a three-particle system, the two-body interaction energies depend upon coordinates of all three particles. The comparative study of the interaction energy and its many-body decomposition for alkaline-earths tetramers Be4, Mg4, and Ca4 at the all-electron CCSD(T)/aug-cc-pVQZ level is performed. For study of dependence of the binding energy and the orbital population on the cluster size the corresponding dimers and trimers were also calculated at the same level of theory. In comparison with weakly bound dimers, the binding energy in trimers and, especially, in tetramers drastically increases; e.g., Eb/N in Be3 is 7 times larger and in Be4 is 18.4 times larger than in Be2. This sharp increase is explained as a manifestation of many-body forces. The trimers and tetramers are stabilized by the three-body forces, whereas the two- and four-body forces are repulsive. The attractive contribution to the three-body forces has a three-atom electron exchange origin. The natural bond orbital (NBO) population analysis reveals a relatively large np-population in trimers and tetramers. The population of the valence np-orbitals leads to the sp-hybridization providing the covalent bonding. Research highlights: → The alkaline-earths trimers and tetramers are stabilized by the three-body forces. → Two- and four-body forces are repulsive for trimers and tetramers. → The attractive contribution to the three-body forces has a three-atom electron exchange origin. → The population of the np-orbitals leads to the sp-hybridization providing the covalent bonding. - Abstract: The comparative study of the interaction energy and its many-body decomposition for Be4, Mg4, and Ca4 at the all-electron CCSD(T)/aug-cc-pVQZ level is performed. For study of dependence of the binding energy and the orbital population on the cluster size the corresponding dimers and trimers were also calculated at the same level of theory. In comparison with weakly

  9. Many-body forces and stability of the alkaline-earth tetramers

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Torrejon, C.C. [Centro Nacional de Supercomputo, IPICyT, A.C., Camino a la Presa San Jose 2055, 78216 San Luis Potosi, SLP (Mexico); Centro de Investigacion en Materiales Avanzados, S.C., Av. Miguel de Cervantes 120, 31109 Chihuahua, Chih. (Mexico); Kaplan, Ilya G., E-mail: kaplan@iim.unam.mx [Instituto de Investigaciones en Materiales, UNAM, Apdo. Postal 70-360, 04510 Mexico D.F. (Mexico)

    2011-03-18

    Graphical abstract: Many-body forces effect. In a three-particle system, the two-body interaction energies depend upon coordinates of all three particles. The comparative study of the interaction energy and its many-body decomposition for alkaline-earths tetramers Be{sub 4}, Mg{sub 4}, and Ca{sub 4} at the all-electron CCSD(T)/aug-cc-pVQZ level is performed. For study of dependence of the binding energy and the orbital population on the cluster size the corresponding dimers and trimers were also calculated at the same level of theory. In comparison with weakly bound dimers, the binding energy in trimers and, especially, in tetramers drastically increases; e.g., E{sub b}/N in Be{sub 3} is 7 times larger and in Be{sub 4} is 18.4 times larger than in Be{sub 2}. This sharp increase is explained as a manifestation of many-body forces. The trimers and tetramers are stabilized by the three-body forces, whereas the two- and four-body forces are repulsive. The attractive contribution to the three-body forces has a three-atom electron exchange origin. The natural bond orbital (NBO) population analysis reveals a relatively large np-population in trimers and tetramers. The population of the valence np-orbitals leads to the sp-hybridization providing the covalent bonding. Research highlights: {yields} The alkaline-earths trimers and tetramers are stabilized by the three-body forces. {yields} Two- and four-body forces are repulsive for trimers and tetramers. {yields} The attractive contribution to the three-body forces has a three-atom electron exchange origin. {yields} The population of the np-orbitals leads to the sp-hybridization providing the covalent bonding. - Abstract: The comparative study of the interaction energy and its many-body decomposition for Be{sub 4}, Mg{sub 4}, and Ca{sub 4} at the all-electron CCSD(T)/aug-cc-pVQZ level is performed. For study of dependence of the binding energy and the orbital population on the cluster size the corresponding dimers and

  10. Structural Plasticity of the Protein Plug That Traps Newly Packaged Genomes in Podoviridae Virions.

    Science.gov (United States)

    Bhardwaj, Anshul; Sankhala, Rajeshwer S; Olia, Adam S; Brooke, Dewey; Casjens, Sherwood R; Taylor, Derek J; Prevelige, Peter E; Cingolani, Gino

    2016-01-01

    Bacterial viruses of the P22-like family encode a specialized tail needle essential for genome stabilization after DNA packaging and implicated in Gram-negative cell envelope penetration. The atomic structure of P22 tail needle (gp26) crystallized at acidic pH reveals a slender fiber containing an N-terminal "trimer of hairpins" tip. Although the length and composition of tail needles vary significantly in Podoviridae, unexpectedly, the amino acid sequence of the N-terminal tip is exceptionally conserved in more than 200 genomes of P22-like phages and prophages. In this paper, we used x-ray crystallography and EM to investigate the neutral pH structure of three tail needles from bacteriophage P22, HK620, and Sf6. In all cases, we found that the N-terminal tip is poorly structured, in stark contrast to the compact trimer of hairpins seen in gp26 crystallized at acidic pH. Hydrogen-deuterium exchange mass spectrometry, limited proteolysis, circular dichroism spectroscopy, and gel filtration chromatography revealed that the N-terminal tip is highly dynamic in solution and unlikely to adopt a stable trimeric conformation at physiological pH. This is supported by the cryo-EM reconstruction of P22 mature virion tail, where the density of gp26 N-terminal tip is incompatible with a trimer of hairpins. We propose the tail needle N-terminal tip exists in two conformations: a pre-ejection extended conformation, which seals the portal vertex after genome packaging, and a postejection trimer of hairpins, which forms upon its release from the virion. The conformational plasticity of the tail needle N-terminal tip is built in the amino acid sequence, explaining its extraordinary conservation in nature. PMID:26574546

  11. The growth of sulfur adlayers on Au(100).

    Science.gov (United States)

    Jiang, Yue; Liang, Xihui; Ren, Shendong; Chen, Chi-Lu; Fan, Liang-Jen; Yang, Yaw-Wen; Tang, Jian-Ming; Luh, Dah-An

    2015-02-14

    We have studied the growth of S layers adsorbed on Au(100) with low-energy electron diffraction (LEED), X-ray photoemission spectra (XPS), and scanning tunneling microscope (STM). Three phases of S/Au(100)-(2 × 2), trimer, and c(2 × 4)-are identified; the latter two are not previously reported. A dose of S2 at 300 K transformed Au(100)-(5 × 20) initially into the (2 × 2) phase and formed the c(2 × 4) phase at a saturation coverage. The STM results show that monolayer Au islands formed during the initial S dose and remained throughout the growth, resulting in a rough c(2 × 4) surface. We show that a highly ordered c(2 × 4) phase can be obtained with a flat (2 × 2) phase as an intermediate step during growth. Based on the evolution of XPS and STM images with varied S2 dose, the components of S 2p are assigned and structural models for the various S/Au(100) phases are proposed. In the (2 × 2) phase, one S atom resides on a four-fold hollow site in each (2 × 2) unit cell, corresponding to a S coverage of 0.25 ML; in the trimer phase, three S atoms form a trimer residing on a four-fold hollow site in each (2 × 2) unit cell, corresponding to a S coverage of 0.75 ML; in the c(2 × 4) phase, there are five S atoms in each primitive unit cell of c(2 × 4); three of them form a trimer residing on a four-fold hollow site, and the other two form a dimer located on the top of the trimer, corresponding to a nominal S coverage of 1.25 ML. With the proposed structural models, the growth of S on Au(100) at 300 K is described in detail. PMID:25681936

  12. The Structure of the Complex between Yeast Frataxin and Ferrochelatase: CHARACTERIZATION AND PRE-STEADY STATE REACTION OF FERROUS IRON DELIVERY AND HEME SYNTHESIS.

    Science.gov (United States)

    Söderberg, Christopher; Gillam, Mallory E; Ahlgren, Eva-Christina; Hunter, Gregory A; Gakh, Oleksandr; Isaya, Grazia; Ferreira, Gloria C; Al-Karadaghi, Salam

    2016-05-27

    Frataxin is a mitochondrial iron-binding protein involved in iron storage, detoxification, and delivery for iron sulfur-cluster assembly and heme biosynthesis. The ability of frataxin from different organisms to populate multiple oligomeric states in the presence of metal ions, e.g. Fe(2+) and Co(2+), led to the suggestion that different oligomers contribute to the functions of frataxin. Here we report on the complex between yeast frataxin and ferrochelatase, the terminal enzyme of heme biosynthesis. Protein-protein docking and cross-linking in combination with mass spectroscopic analysis and single-particle reconstruction from negatively stained electron microscopic images were used to verify the Yfh1-ferrochelatase interactions. The model of the complex indicates that at the 2:1 Fe(2+)-to-protein ratio, when Yfh1 populates a trimeric state, there are two interaction interfaces between frataxin and the ferrochelatase dimer. Each interaction site involves one ferrochelatase monomer and one frataxin trimer, with conserved polar and charged amino acids of the two proteins positioned at hydrogen-bonding distances from each other. One of the subunits of the Yfh1 trimer interacts extensively with one subunit of the ferrochelatase dimer, contributing to the stability of the complex, whereas another trimer subunit is positioned for Fe(2+) delivery. Single-turnover stopped-flow kinetics experiments demonstrate that increased rates of heme production result from monomers, dimers, and trimers, indicating that these forms are most efficient in delivering Fe(2+) to ferrochelatase and sustaining porphyrin metalation. Furthermore, they support the proposal that frataxin-mediated delivery of this potentially toxic substrate overcomes formation of reactive oxygen species. PMID:27026703

  13. Multimerized HIV-gp41-derived peptides as fusion inhibitors and vaccines.

    Science.gov (United States)

    Nomura, Wataru; Mizuguchi, Takaaki; Tamamura, Hirokazu

    2016-11-01

    To date, several antigens based on the amino-terminal leucine/isoleucine heptad repeat (NHR) region of an HIV-1 envelope protein gp41 and fusion inhibitors based on the carboxy-terminal leucine/isoleucine heptad repeat (CHR) region of gp41 have been reported. We have developed a synthetic antigen targeting the membrane-fusion mechanism of HIV-1. This uses a template designed with C3-symmetric linkers and mimics the trimeric form of the NHR-derived peptide N36. The antiserum obtained by immunization of the N36 trimeric antigen binds preferentially to the N36 trimer and blocks HIV-1 infection effectively, compared with the antiserum obtained by immunization of the N36 monomer. Using another template designed with different C3-symmetric linkers, we have also developed a synthetic peptide mimicking the trimeric form of the CHR-derived peptide C34, with ∼100 times the inhibitory activity against the HIV-1 fusion mechanism than that of the monomer C34 peptide. A dimeric derivative of C34 has potent inhibitory activity at almost the same levels as this C34 trimer mimic, suggesting that presence of a dimeric form of C34 is structurally critical for fusion inhibitors. As examples of rising mid-size drugs, this review describes an effective strategy for the design of HIV vaccines and fusion inhibitors based on a relationship with the native structure of proteins involved in HIV fusion mechanisms. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 622-628, 2016. PMID:26583370

  14. Identification of an additional class of C3-binding membrane proteins of human peripheral blood leukocytes and cell lines.

    Science.gov (United States)

    Cole, J L; Housley, G A; Dykman, T R; MacDermott, R P; Atkinson, J P

    1985-02-01

    Proteins binding the third component of complement (C3) were isolated by affinity chromatography from surface-labeled solubilized membranes of human peripheral blood cells and cell lines. The isolated molecules were subjected to NaDodSO4/PAGE, and autoradiographs of these gels indicated that C3-binding proteins could be divided into three groups based on Mr: (i) gp200, an approximately 200,000 Mr molecule previously identified as the C3b/C4b receptor or CR1; (ii) gp140, an approximately 140,000 Mr molecule previously identified as the C3d receptor or CR2; and (iii) gp45-70, a heretofore unrecognized group of 45,000-70,000 Mr C3-binding molecules. The cell distribution, Mr, antigenic cross-reactivity, and specificity of gp45-70 were examined. Erythrocytes have no detectable gp45-70, but all leukocyte populations examined possess this group of molecules. On neutrophils and mononuclear phagocytes, CR1 is the predominant C3-binding glycoprotein, but gp45-70 is present on both cell populations and on macrophage and neutrophil cell lines. B plus null cells, chronic lymphocytic leukemia cells, and an Epstein-Barr virus-transformed B-cell line possess CR1, CR2, and gp45-70. On T cells and T-cell lines gp45-70 is the predominant or, in some cases, the only C3-binding protein isolated. gp45-70 is structurally characterized as a broad band or doublet with a mean Mr that is slightly different for each cell population. gp45-70 binds iC3, C3b, and C4b, but not C3d, indicating that the binding region is probably within the C3c portion of C3b. A polyclonal antibody to CR1 and monoclonal antibodies to CR1 and CR2 do not immunoprecipitate gp45-70. While gp45-70 has not been previously characterized on human cells, a C3b-binding glycoprotein of similar Mr is present on rabbit alveolar macrophages. We conclude that gp45-70 is an additional group of membrane proteins present on human leukocytes that possess ligand-binding activity for C3b. PMID:3871945

  15. Comparación de la antigenicidad de un peptido sintetico y una proteína recombinante de la región de transmembrana (gp 36 del VIH-2

    Directory of Open Access Journals (Sweden)

    Milenen Hernández Marin

    2009-01-01

    Full Text Available El virus de la inmunodeficiencia humana del tipo 2 (VIH-2 se detectó en países de África Occidental y es otro agente causal del Síndrome de Inmunodeficiencia Adquirida (SIDA. El gen env codifica la síntesis de la proteína precursora, gp140, que es procesada por una proteasa del virus en dos proteínas: gp36 y gp105. Los péptidos sintéticos y proteínas recombinantes de la glicoproteína de la transmembrana gp36 muestran una elevada reactividad y especificidad en la detección de anticuerpos en muestras de pacientes infectados, por lo que son ampliamente utilizadas en el inmunodiagnóstico del VIH-2. En el presente trabajo se evaluó la reactividad de un péptido sintético gp36 (5 (585-610 y la proteína recombinante gp36 de la región de la transmembrana del VIH-2, frente a 15 muestras positivas al VIH-2. La especificidad de estos antígenos se evaluó con 74 muestras de seropositivos cubanos al VIH-1 y 30 sueros de donantes de un banco de sangre. Se utilizó como ensayo de referencia el UMELISA HIV 1+2 Recombinant (TecnoSUMA Internacional S.A., Cuba, para la detección de anticuerpos contra el VIH 1 y 2. Todas las muestras utilizadas en el estudio fueron confirmadas por el ensayo de Western Blot. Se obtuvo un 100 % de reactividad para los dos antígenos. El péptido sintético gp36 (5 no detectó las muestras positivas del VIH-1 evaluadas, a diferencia de la proteína recombinante que detectó un 46 % de estas muestras. La especificidad de los dos antígenos fue de un 100 % frente a las muestras de donantes sanos de un banco de sangre. Este estudio demostró la gran reactividad de la proteína recombinante y el péptido sintético, así como la elevada especificidad de este último frente a muestras positivas al VIH-2.

  16. Cross-Reactive Human IgM-Derived Monoclonal Antibodies that Bind to HIV-1 Envelope Glycoproteins.

    Science.gov (United States)

    Chen, Weizao; Zhu, Zhongyu; Liao, Huaxin; Quinnan, Gerald V; Broder, Christopher C; Haynes, Barton F; Dimitrov, Dimiter S

    2010-02-01

    Elicitation of antibodies with potent and broad neutralizing activity against HIV by immunization remains a challenge. Several monoclonal antibodies (mAbs) isolated from humans with HIV-1 infection exhibit such activity but vaccine immunogens based on structures containing their epitopes have not been successful for their elicitation. All known broadly neutralizing mAbs (bnmAbs) are immunoglobulin (Ig) Gs (IgGs) and highly somatically hypermutated which could impede their elicitation. Ig Ms (IgMs) are on average significantly less divergent from germline antibodies and are relevant for the development of vaccine immunogens but are underexplored compared to IgGs. Here we describe the identification and characterization of several human IgM-derived mAbs against HIV-1 which were selected from a large phage-displayed naive human antibody library constructed from blood, lymph nodes and spleens of 59 healthy donors. These antibodies bound with high affinity to recombinant envelope glycoproteins (gp140s, Envs) of HIV-1 isolates from different clades. They enhanced or did not neutralize infection by some of the HIV-1 primary isolates using CCR5 as a coreceptor but neutralized all CXCR4 isolates tested although weakly. One of these antibodies with relatively low degree of somatic hypermutation was more extensively characterized. It bound to a highly conserved region partially overlapping with the coreceptor binding site and close to but not overlapping with the CD4 binding site. These results suggest the existence of conserved structures that could direct the immune response to non-neutralizing or even enhancing antibodies which may represent a strategy used by the virus to escape neutralizing immune responses. Further studies will show whether such a strategy plays a role in HIV infection of humans, how important that role could be, and what the mechanisms of infection enhancement are. The newly identified mAbs could be used as reagents to further characterize conserved

  17. Cross-Reactive Human IgM-Derived Monoclonal Antibodies that Bind to HIV-1 Envelope Glycoproteins

    Directory of Open Access Journals (Sweden)

    Barton F. Haynes

    2010-02-01

    Full Text Available Elicitation of antibodies with potent and broad neutralizing activity against HIV by immunization remains a challenge. Several monoclonal antibodies (mAbs isolated from humans with HIV-1 infection exhibit such activity but vaccine immunogens based on structures containing their epitopes have not been successful for their elicitation. All known broadly neutralizing mAbs (bnmAbs are immunoglobulin (Ig Gs (IgGs and highly somatically hypermutated which could impede their elicitation. Ig Ms (IgMs are on average significantly less divergent from germline antibodies and are relevant for the development of vaccine immunogens but are underexplored compared to IgGs. Here we describe the identification and characterization of several human IgM-derived mAbs against HIV-1 which were selected from a large phage-displayed naive human antibody library constructed from blood, lymph nodes and spleens of 59 healthy donors. These antibodies bound with high affinity to recombinant envelope glycoproteins (gp140s, Envs of HIV-1 isolates from different clades. They enhanced or did not neutralize infection by some of the HIV-1 primary isolates using CCR5 as a coreceptor but neutralized all CXCR4 isolates tested although weakly. One of these antibodies with relatively low degree of somatic hypermutation was more extensively characterized. It bound to a highly conserved region partially overlapping with the coreceptor binding site and close to but not overlapping with the CD4 binding site. These results suggest the existence of conserved structures that could direct the immune response to non-neutralizing or even enhancing antibodies which may represent a strategy used by the virus to escape neutralizing immune responses. Further studies will show whether such a strategy plays a role in HIV infection of humans, how important that role could be, and what the mechanisms of infection enhancement are. The newly identified mAbs could be used as reagents to further

  18. Characterization of a monoclonal antibody to a novel glycan-dependent epitope in the V1/V2 domain of the HIV-1 envelope protein, gp120.

    Science.gov (United States)

    Doran, Rachel C; Morales, Javier F; To, Briana; Morin, Trevor J; Theolis, Richard; O'Rourke, Sara M; Yu, Bin; Mesa, Kathryn A; Berman, Phillip W

    2014-11-01

    Recent studies have described several broadly neutralizing monoclonal antibodies (bN-mAbs) that recognize glycan-dependent epitopes (GDEs) in the HIV-1 envelope protein, gp120. These were recovered from HIV-1 infected subjects, and several (e.g., PG9, PG16, CH01, CH03) target glycans in the first and second variable (V1/V2) domain of gp120. The V1/V2 domain is thought to play an important role in conformational masking, and antibodies to the V1/V2 domain were recently identified as the only immune response that correlated with protection in the RV144 HIV-1 vaccine trial. While the importance of antibodies to polymeric glycans is well established for vaccines targeting bacterial diseases, the importance of antibodies to glycans in vaccines targeting HIV has only recently been recognized. Antibodies to GDEs may be particularly significant in HIV vaccines based on gp120, where 50% of the molecular mass of the envelope protein is contributed by N-linked carbohydrate. However, few studies have reported antibodies to GDEs in humans or animals immunized with candidate HIV-1 vaccines. In this report, we describe the isolation of a mouse mAb, 4B6, after immunization with the extracellular domain of the HIV-1 envelope protein, gp140. Epitope mapping using glycopeptide fragments and in vitro mutagenesis showed that binding of this antibody depends on N-linked glycosylation at asparagine N130 (HXB2 numbering) in the gp120 V1/V2 domain. Our results demonstrate that, in addition to natural HIV-1 infection, immunization with recombinant proteins can elicit antibodies to the GDEs in the V1/V2 domain of gp120. Although little is known regarding conditions that favor antibody responses to GDEs, our studies demonstrate that these antibodies can arise from a short-term immunization regimen. Our results suggest that antibodies to GDEs are more common than previously suspected, and that further analysis of antibody responses to the HIV-1 envelope protein will lead to the discovery of

  19. Morphological divergence in a continental adaptive radiation: South American ovenbirds of the genus Cinclodes

    Science.gov (United States)

    Rader, Jonathan A.; Dillon, Michael E.; Chesser, Terry; Sabat, Pablo; Martinez del Rio, Carlos

    2015-01-01

    Cinclodes is an ecologically diverse genus of South American passerine birds and represents a case of continental adaptive radiation along multiple axes. We investigated morphological diversification in Cinclodes using a comprehensive set of morphometric measurements of study skins. Principal component analysis identified 2 primary axes of morphological variation: one describing body size and a second capturing differences in wing-tip shape and toe length. Phylogenetic analyses of the first principal component suggest an early divergence ofCinclodes into 2 main clades characterized by large and small body sizes. We suggest that 2 morphological outliers within these main clades (C. antarcticus and C. palliatus) may be cases of island gigantism and that a third (C. patagonicus) may reflect ecological character displacement. Despite its ecological and physiological diversity, the genus Cinclodes does not appear to show morphological diversity beyond what is typical of other avian genera.

  20. Molecular phylogeny and community fingerprinting of coral-associated Symbiodinium north of the Arabian Gulf.

    Science.gov (United States)

    Mahmoud, Huda M; Al-Sarraf, Mohammad

    2016-07-15

    Understanding coral-Symbiodinium relationships including changes in the genotypes and the numbers of Symbiodinium can explain the ability of Kuwait coral to survive high fluctuations in water temperature. In the current study, the diversity of Symbiodinium associated with fourteen coral species from six reef systems south of Kuwait was investigated. The results proved the predominance of clade C members in all corals tested, which reflects the importance of this type in helping corals thrive in the Gulf's harsh conditions. Platygyra daedalea was the only coral found that harbored clades A, B and C in their tissue but it is the most vulnerable coral for bleaching. The total number of Symbiodinium-like cells in the seawater was 10(4) cell ml(-1) while in coral tissue and mucus 10(7) cell g(-1) and 10(7) cell ml(-1) were found, respectively, and a strong positive correlation with the seawater temperature, salinity and conductivity was found. PMID:27179998

  1. Similar Neutralizing Activity in the HIV-1 Infected Long Term Non-progressors(LTNPs) and Typical Progressors(TPs)

    Institute of Scientific and Technical Information of China (English)

    Zheng Wang; Si-yang Liu; Lin Li; Tian-yi Li; Jing-yun Li; Li-li Chen; Yong-jian Liu; Han-ping Li; Zuo-yi Bao; Xiao-lin Wang; Dao-min Zhuang

    2012-01-01

    Neutralizing antibodies are considered to be an important protective parameter used in HIV-l vaccine evaluation.However,the exact role that neutralizing antibodies plays in controlling the disease progression of HIV-1 infected peoples is still undetermined.In this paper,we compared the protective function of the neutralizing antibody response in the plasma from LTNP and TP against clade B and clade C pseudoviruses.No difference in the neutralizing activities between the plasma from LTNP and TP was found,which was consistent with the most recent reports.In addition,no correlations between the titer or breadth and CD4+ or viral load in HIV-1 infected individuals were found.The protective roles played by neutralizing antibodies in controlling disease progression of HIV-1 infected people need to be considered in a new viewpoint.

  2. Phylogenetic relationships of the marine Haplosclerida (Phylum Porifera) employing ribosomal (28S rRNA) and mitochondrial (cox1, nad1) gene sequence data.

    Science.gov (United States)

    Redmond, Niamh E; Raleigh, Jean; van Soest, Rob W M; Kelly, Michelle; Travers, Simon A A; Bradshaw, Brian; Vartia, Salla; Stephens, Kelly M; McCormack, Grace P

    2011-01-01

    The systematics of the poriferan Order Haplosclerida (Class Demospongiae) has been under scrutiny for a number of years without resolution. Molecular data suggests that the order needs revision at all taxonomic levels. Here, we provide a comprehensive view of the phylogenetic relationships of the marine Haplosclerida using many species from across the order, and three gene regions. Gene trees generated using 28S rRNA, nad1 and cox1 gene data, under maximum likelihood and Bayesian approaches, are highly congruent and suggest the presence of four clades. Clade A is comprised primarily of species of Haliclona and Callyspongia, and clade B is comprised of H. simulans and H. vansoesti (Family Chalinidae), Amphimedon queenslandica (Family Niphatidae) and Tabulocalyx (Family Phloeodictyidae), Clade C is comprised primarily of members of the Families Petrosiidae and Niphatidae, while Clade D is comprised of Aka species. The polyphletic nature of the suborders, families and genera described in other studies is also found here. PMID:21931685

  3. Temporal stability of Symbiodinium phylotype in scleractinian coral Galaxea fascicularis from a tropical fringing reef in the South China Sea

    Science.gov (United States)

    Zhou, Guowei; Huang, Hui; Dong, Zhijun; Yu, Ziniu

    2011-11-01

    Symbiodinium sp. occurs in a symbiotic association with various marine invertebrates, including the scleractinian corals. Understanding the flexibility and specificity in coral-algal symbiosis can have important implications for predicting the future of coral reefs in the era of global climate change. In the present study, we conducted Symbiodinium phylotype analysis, based on polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), in the scleractinian coral, Galaxea fascicularis, from a tropical fringing reef in Hainan Island, over a 1-yr period. Our results showed that Galaxea fascicularis could associate with Symbiodinium clade C and D either individually or simultaneously. However, during the sampling period, the Symbiodinium phylotype did not change significantly in the scleractinian coral Galaxea fascicularis, although the seawater temperature decreased sharply in the winter season. This study further suggests that the shift in Symbiodinium communities in response to seasonally fluctuating environments might not be a universal feature of coral-algal associations.

  4. Re-evaluating the taxonomic status of Chiromantis in Thailand using multiple lines of evidence (Amphibia: Anura: Rhacophoridae).

    Science.gov (United States)

    Aowphol, Anchalee; Rujirawan, Attapol; Taksintum, Wut; Arsirapot, Sutipong; McLeod, David S

    2013-01-01

    Because of general phenotypic similarities and distribution of species across two continents, the genus Chiromantis has proven somewhat enigmatic. Among Indochinese species, the validity of C. hansenae has been questioned by some who consider it a junior synonym of C. vittatus. We employ three lines of evidence to elucidate the taxonomic status and phylogenetic relationships of four congeneric species of Chiromantis frogs from Thailand. Results of molecular, morphological, and bioacoustic data analyses support at least four evolutionarily distinct and monophyletic clades: C. doriae, C. nongkhorensis, C. vittatus and C. hansenae. Genetic divergence between C. vittatus and C. hansenae is > 10%, significantly greater than C. doriae and C nongkhorensis (4.5%). Our results support the taxonomic validity of C. hansenae and suggest that there may be more diversity within C. hansenae and C. vittatus than is currently recognized. PMID:26146711

  5. Spectral Reflectance of Palauan Reef-Building Coral with Different Symbionts in Response to Elevated Temperature

    Directory of Open Access Journals (Sweden)

    Brandon J. Russell

    2016-02-01

    Full Text Available Spectral reflectance patterns of corals are driven largely by the pigments of photosynthetic symbionts within the host cnidarian. The warm inshore bays and cooler offshore reefs of Palau share a variety of coral species with differing endosymbiotic dinoflagellates (genus: Symbiodinium, with the thermally tolerant Symbiodinium trenchii (S. trenchii (= type D1a or D1-4 predominating under the elevated temperature regimes inshore, and primarily Clade C types in the cooler reefs offshore. Spectral reflectance of two species of stony coral, Cyphastrea serailia (C. serailia and Pachyseris rugosa (P. rugosa, from both inshore and offshore locations shared multiple features both between sites and to similar global data from other studies. No clear reflectance features were evident which might serve as markers of thermally tolerant S. trenchii symbionts compared to the same species of coral with different symbionts. Reflectance from C. serailia colonies from inshore had a fluorescence peak at approximately 500 nm which was absent from offshore animals. Integrated reflectance across visible wavelengths had an inverse correlation to symbiont cell density and could be used as a relative indicator of the symbiont abundance for each type of coral. As hypothesized, coral colonies from offshore with Clade C symbionts showed a greater response to experimental heating, manifested as decreased symbiont density and increased reflectance or “bleaching” than their inshore counterparts with S. trenchii. Although no unique spectral features were found to distinguish species of symbiont, spectral differences related to the abundance of symbionts could prove useful in field and remote sensing studies.

  6. Diversity and distribution of symbiodinium associated with seven common coral species in the Chagos Archipelago, central Indian Ocean.

    Directory of Open Access Journals (Sweden)

    Sung-Yin Yang

    Full Text Available The Chagos Archipelago designated as a no-take marine protected area in 2010, lying about 500 km south of the Maldives in the Indian Ocean, has a high conservation priority, particularly because of its fast recovery from the ocean-wide massive coral mortality following the 1998 coral bleaching event. The aims of this study were to examine Symbiodinium diversity and distribution associated with scleractinian corals in five atolls of the Chagos Archipelago, spread over 10,000 km(2. Symbiodinium clade diversity in 262 samples of seven common coral species, Acropora muricata, Isopora palifera, Pocillopora damicornis, P. verrucosa, P. eydouxi, Seriatopora hystrix, and Stylophora pistillata were determined using PCR-SSCP of the ribosomal internal transcribed spacer 1 (ITS1, PCR-DDGE of ITS2, and phylogenetic analyses. The results indicated that Symbiodinium in clade C were the dominant symbiont group in the seven coral species. Our analysis revealed types of Symbiodinium clade C specific to coral species. Types C1 and C3 (with C3z and C3i variants were dominant in Acroporidae and C1 and C1c were the dominant types in Pocilloporidae. We also found 2 novel ITS2 types in S. hystrix and 1 novel ITS2 type of Symbiodinium in A. muricata. Some colonies of A. muricata and I. palifera were also associated with Symbiodinium A1. These results suggest that corals in the Chagos Archipelago host different assemblages of Symbiodinium types then their conspecifics from other locations in the Indian Ocean; and that future research will show whether these patterns in Symbiodinium genotypes may be due to local adaptation to specific conditions in the Chagos.

  7. Flail arm-like syndrome associated with HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Nalini A

    2009-01-01

    Full Text Available During the last 20 years at least 23 cases of motor neuron disease have been reported in HIV-1 seropositive patients. In this report we describe the clinical picture of a young man with HIV-1 clade C infection and flail arm-like syndrome, who we were able to follow-up for a long period. We investigated and prospectively monitored a 34-year-old man with features of flail arm syndrome, who developed the weakness and wasting 1 year after being diagnosed with HIV-1 infection after a routine blood test. He presented in 2003 with progressive, symmetrical wasting and weakness of the proximal muscles of the upper limb of 2 years′ duration. He had severe wasting and weakness of the shoulder and arm muscles. There were no pyramidal signs. He has been on HAART for the last 4 years and the weakness or wasting has not worsened. At the last follow-up in July 2007, the patient had the same neurological deficit and no other symptoms or signs of HIV-1 infection. MRI of the spinal cord in 2007 showed characteristic T2 hyperintense signals in the central part of the spinal cord, corresponding to the central gray matter. Thus, our patient had HIV-1 clade C infection associated with a ′flail arm-like syndrome.′ The causal relationship between HIV-1 infection and amyotrophic lateral sclerosis (ALS-like syndrome is still uncertain. The syndrome usually manifests as a lower motor neuron syndrome, as was seen in our young patient. It is known that treatment with antiretroviral therapy (ART stabilizes/improves the condition. In our patient the weakness and atrophy remained stable over a period of 3.5 years after commencing HAART regimen.

  8. Flail arm–like syndrome associated with HIV-1 infection

    Science.gov (United States)

    Nalini, A.; Desai, Anita; Mahato, Simendra Kumar

    2009-01-01

    During the last 20 years at least 23 cases of motor neuron disease have been reported in HIV-1 seropositive patients. In this report we describe the clinical picture of a young man with HIV-1 clade C infection and flail arm-like syndrome, who we were able to follow-up for a long period. We investigated and prospectively monitored a 34-year-old man with features of flail arm syndrome, who developed the weakness and wasting 1 year after being diagnosed with HIV-1 infection after a routine blood test. He presented in 2003 with progressive, symmetrical wasting and weakness of the proximal muscles of the upper limb of 2 years' duration. He had severe wasting and weakness of the shoulder and arm muscles. There were no pyramidal signs. He has been on HAART for the last 4 years and the weakness or wasting has not worsened. At the last follow-up in July 2007, the patient had the same neurological deficit and no other symptoms or signs of HIV-1 infection. MRI of the spinal cord in 2007 showed characteristic T2 hyperintense signals in the central part of the spinal cord, corresponding to the central gray matter. Thus, our patient had HIV-1 clade C infection associated with a ‘flail arm–like syndrome.’ The causal relationship between HIV-1 infection and amyotrophic lateral sclerosis (ALS)-like syndrome is still uncertain. The syndrome usually manifests as a lower motor neuron syndrome, as was seen in our young patient. It is known that treatment with antiretroviral therapy (ART) stabilizes/improves the condition. In our patient the weakness and atrophy remained stable over a period of 3.5 years after commencing HAART regimen. PMID:20142861

  9. Imported Asian swamp eels (Synbranchidae: Monopterus) in North American live food markets: Potential vectors of non-native parasites

    Science.gov (United States)

    Nico, Leo G.; Sharp, Paul; Collins, Timothy M.

    2011-01-01

    Since the 1990s, possibly earlier, large numbers of Asian swamp eels (Synbranchidae: Monopterus spp.), some wild-caught, have been imported live from various countries in Asia and sold in ethnic food markets in cities throughout the USA and parts of Canada. Such markets are the likely introduction pathway of some, perhaps most, of the five known wild populations of Asian swamp eels present in the continental United States. This paper presents results of a pilot study intended to gather baseline data on the occurrence and abundance of internal macroparasites infecting swamp eels imported from Asia to North American retail food markets. These data are important in assessing the potential role that imported swamp eels may play as possible vectors of non-native parasites. Examination of the gastrointestinal tracts and associated tissues of 19 adult-sized swamp eels—identified as M. albus "Clade C"—imported from Vietnam and present in a U.S. retail food market revealed that 18 (95%) contained macroparasites. The 394 individual parasites recovered included a mix of nematodes, acanthocephalans, cestodes, digeneans, and pentastomes. The findings raise concern because of the likelihood that some parasites infecting market swamp eels imported from Asia are themselves Asian taxa, some possibly new to North America. The ecological risk is exacerbated because swamp eels sold in food markets are occasionally retained live by customers and a few reportedly released into the wild. For comparative purposes, M. albus "Clade C" swamp eels from a non-native population in Florida (USA) were also examined and most (84%) were found to be infected with internal macroparasites. The current level of analysis does not allow us to confirm whether these are non-native parasites.

  10. Flexible associations between Pocillopora corals and Symbiodinium limit utility of symbiosis ecology in defining species

    Science.gov (United States)

    Cunning, R.; Glynn, P. W.; Baker, A. C.

    2013-09-01

    Corals in the genus Pocillopora are the primary framework builders of eastern tropical Pacific (ETP) reefs. These corals typically associate with algal symbionts (genus Symbiodinium) in clade C and/or D, with clade D associations having greater thermal tolerance and resistance to bleaching. Recently, cryptic "species" delineations within both Pocillopora and Symbiodinium have been suggested, with host-symbiont specificity used as a supporting taxonomic character in both genera. In particular, it has been suggested that three lineages of Pocillopora (types 1-3) exist in the ETP, of which type 1 is the exclusive host of heat-tolerant Symbiodinium D1. This host specificity has been used to support the species name " Symbiodinium glynni" for this symbiont. To validate these host-symbiont relationships and their taxonomic utility, we identified Pocillopora types and their associated Symbiodinium at three sites in the ETP. We found greater flexibility in host-symbiont combinations than previously reported, with both Pocillopora types 1 and 3 able to host and be dominated by Symbiodinium in clade C or D. The prevalence of certain combinations did vary among sites, showing that a gradient of specificity exists which may be mediated by evolutionary relationships and environmental disturbance history. However, these results limit the utility of apparent host-symbiont specificity (which may have been a result of undersampling) in defining species boundaries in either corals or Symbiodinium. They also suggest that a greater diversity of corals may benefit from the thermal tolerance of clade D symbionts, affirming the need to conserve Pocillopora across its entire geographic and environmental range.

  11. Supramolecular 2D/3D isomerism in a compound containing heterometallic Cu(II)2Co(II) nodes and dicyanamide bridges.

    Science.gov (United States)

    Biswas, Saptarshi; Gómez-García, Carlos J; Clemente-Juan, Juan M; Benmansour, Samia; Ghosh, Ashutosh

    2014-03-01

    Three new heterometallic copper(II)-cobalt(II) complexes [(CuL(2))2Co{dca}2]·H2O(1), [(CuL(1))2Co{dca}2]n (2a), and [(CuL(1))2Co{dca}2]n (2b) [dca(-) = dicyanamide = N(CN)2(-)] have been synthesized by reacting the "metallo-ligand" [CuL(1)] or [CuL(2)] with cobalt(II) perchlorate and sodium dicyanamide in methanol-water medium (where H2L(1) = N,N'-bis(salicylidene)-1,3-propanediamine and H2L(2) = N,N'-bis(α-methylsalicylidene)-1,3-propanediamine). The three complexes have been structurally and magnetically characterized. Complex 1 is a discrete trinuclear species in which two metallo-ligands coordinate to a cobalt(II) ion through the phenoxido oxygen atoms along with two terminally coordinated dicyanamide ions. On the other hand, complexes 2a and 2b are one of the very scarce examples of supramolecular isomers since they present the same [(CuL(1))2Co{dca}2] trinuclear units (very similar to the trinuclear core in 1) and differ only in their superstructures. Thus, although each Cu2Co trimer in 2a and 2b is connected to four other Cu2Co trimers through four μ1,5-dca(-) bridges, 2a presents a square two-dimensional structure (each Cu2Co trimer is connected to four in-plane Cu2Co trimers); whereas, 2b shows a triangular three-dimensional lattice (each Cu2Co trimer is connected to three in-plane and one out-of-plane trimers). Variable-temperature magnetic susceptibility measurements show the presence of moderate antiferromagnetic exchange interactions (ferrimagnetic) in all the cases mediated through the double phenoxido bridges that have been fitted with an anisotropic model including spin-orbit coupling in the central Co(II) ion. PMID:24552535

  12. Structure-Based Design of Head-Only Fusion Glycoprotein Immunogens for Respiratory Syncytial Virus

    Science.gov (United States)

    Boyington, Jeffrey C.; Chen, Man; Kong, Wing-Pui; Ngwuta, Joan O.; Thomas, Paul V.; Tsybovsky, Yaroslav; Yang, Yongping; Zhang, Baoshan; Chen, Lei; Druz, Aliaksandr; Georgiev, Ivelin S.; Ko, Kiyoon; Zhou, Tongqing; Mascola, John R.; Graham, Barney S.; Kwong, Peter D.

    2016-01-01

    Respiratory syncytial virus (RSV) is a significant cause of severe respiratory illness worldwide, particularly in infants, young children, and the elderly. Although no licensed vaccine is currently available, an engineered version of the metastable RSV fusion (F) surface glycoprotein—stabilized in the pre-fusion (pre-F) conformation by “DS-Cav1” mutations—elicits high titer RSV-neutralizing responses. Moreover, pre-F-specific antibodies, often against the neutralization-sensitive antigenic site Ø in the membrane-distal head region of trimeric F glycoprotein, comprise a substantial portion of the human response to natural RSV infection. To focus the vaccine-elicited response to antigenic site Ø, we designed a series of RSV F immunogens that comprised the membrane-distal head of the F glycoprotein in its pre-F conformation. These “head-only” immunogens formed monomers, dimers, and trimers. Antigenic analysis revealed that a majority of the 70 engineered head-only immunogens displayed reactivity to site Ø-targeting antibodies, which was similar to that of the parent RSV F DS-Cav1 trimers, often with increased thermostability. We evaluated four of these head-only immunogens in detail, probing their recognition by antibodies, their physical stability, structure, and immunogenicity. When tested in naïve mice, a head-only trimer, half the size of the parent RSV F trimer, induced RSV titers, which were statistically comparable to those induced by DS-Cav1. When used to boost DS-Cav1-primed mice, two head-only RSV F immunogens, a dimer and a trimer, boosted RSV-neutralizing titers to levels that were comparable to those boosted by DS-Cav1, although with higher site Ø-directed responses. Our results provide proof-of-concept for the ability of the smaller head-only RSV F immunogens to focus the vaccine-elicited response to antigenic site Ø. Decent primary immunogenicity, enhanced physical stability, potential ease of manufacture, and potent immunogenicity

  13. Single Molecule Spectroscopy on Photosynthetic Pigment-Protein Complexes

    CERN Document Server

    Jelezko, F; Schuler, S; Thews, E; Tietz, C; Wechsler, A; Wrachtrup, J

    2001-01-01

    Single molecule spectroscopy was applied to unravel the energy transfer pathway in photosynthetic pigment-protein complexes. Detailed analysis of excitation and fluorescence emission spectra has been made for peripheral plant antenna LHC II and Photosystem I from cyanobacterium Synechococcus elongatus. Optical transitions of individual pigments were resolved under nonselective excitation of antenna chlorophylls. High-resolution fluorescence spectroscopy of individual plant antenna LHC II indicates that at low temperatures, the excitation energy is localized on the red-most Chl a pool absorbing at 680 nm. More than one pigment molecule is responsible for the fluorescence emission of the LHC II trimer. The spectral lines of single Chl a molecules absorbing at 675 nm are broadened because of the Foerster energy transfer towards the red-most pigments. Low-temperature spectroscopy on single PS I trimers indicates that two subgroups of pigments, which are present in the red antenna pool, differ by the strength of t...

  14. 2,3,4,5-Tetra­fluoro­benzoic acid–4,4′-bipyridine (2/1)

    OpenAIRE

    Zhu, Xiaohui

    2009-01-01

    The asymmetric unit of the title compound, 2C7H2F4O2·C10H8N2, contains one mol­ecule of 2,3,4,5-tetra­fluoro­benzoic acid (tfb) and half of a centrosymmetric 4,4′-bipyridine mol­ecule. Inter­molecular O—H⋯N hydrogen bonds link two tfb mol­ecules and one 4,4′-bipyridine mol­ecule into a trimer. Weak inter­molecular C—H⋯F inter­actions assemble these trimers into a three-dimensional network structure.

  15. Structural Insights into Divalent Cation Modulations of ATP-Gated P2X Receptor Channels.

    Science.gov (United States)

    Kasuya, Go; Fujiwara, Yuichiro; Takemoto, Mizuki; Dohmae, Naoshi; Nakada-Nakura, Yoshiko; Ishitani, Ryuichiro; Hattori, Motoyuki; Nureki, Osamu

    2016-02-01

    P2X receptors are trimeric ATP-gated cation channels involved in physiological processes ranging widely from neurotransmission to pain and taste signal transduction. The modulation of the channel gating, including that by divalent cations, contributes to these diverse physiological functions of P2X receptors. Here, we report the crystal structure of an invertebrate P2X receptor from the Gulf Coast tick Amblyomma maculatum in the presence of ATP and Zn(2+) ion, together with electrophysiological and computational analyses. The structure revealed two distinct metal binding sites, M1 and M2, in the extracellular region. The M1 site, located at the trimer interface, is responsible for Zn(2+) potentiation by facilitating the structural change of the extracellular domain for pore opening. In contrast, the M2 site, coupled with the ATP binding site, might contribute to regulation by Mg(2+). Overall, our work provides structural insights into the divalent cation modulations of P2X receptors. PMID:26804916

  16. Oligomerization of mannan-binding lectin dictates binding properties and complement activation

    DEFF Research Database (Denmark)

    Kjaer, Troels R; Jensen, Lisbeth; Hansen, Annette;

    2016-01-01

    altered self-surfaces. Associated with the collagen-like stems of these PRMs are three mannan-binding lectin (MBL)-associated serine proteases (MASPs) and two MBL-associated proteins (MAps). The most studied of the PRMs, MBL, is present in serum mainly as trimeric and tetrameric oligomers of the...... structural subunit. We hypothesized that oligomerization of MBL may influence both the potential to bind to microorganisms and the interaction with the MASPs and MAps, thus influencing the ability to initiate complement activation. When testing binding at 37°C, we found higher binding of tetrameric MBL to...... Staphylococcus aureus (S. aureus) than trimeric and dimeric MBL. In serum, we found that tetrameric MBL was the main oligomeric form present in complexes with the MASPs and MAp44. Such preference was confirmed using purified forms of recombinant MBL (rMBL) oligomers, where tetrameric rMBL interacted stronger...

  17. Structural Elucidation of α-Cyclodextrin-Succinic Acid Pseudo Dodecahydrate: Expanding the Packing Types of α-Cyclodextrin Inclusion Complexes

    Directory of Open Access Journals (Sweden)

    Sofiane Saouane

    2015-12-01

    Full Text Available This paper reports a new packing type of α-cyclodextrin inclusion complexes, obtained here with succinic acid under low-temperature crystallization conditions. The structure of the 1:1 complex is characterized by heavy disorder of the guest, the solvent, and part of the host. The crystal packing belongs to the known channel-type structure; the basic structural unit is composed of cyclodextrin trimers, as opposed to the known isolated molecular or dimeric constructs, packed along the c-axis. Each trimer is made of crystallographically independent molecules assembled in a stacked vase-like cluster. A multi-temperature single-crystal X-ray diffraction analysis reveals the presence of dynamic disorder.

  18. Polarization-dependent single-molecule spectroscopy on photosystem I

    Science.gov (United States)

    Skandary, S.; Konrad, A.; Hussels, M.; Meixner, A. J.; Brecht, M.

    2015-08-01

    Single-molecule spectroscopy (SMS) at low temperature was used to study the spectral properties, heterogeneities and spectral dynamics of the chlorophyll a (Chl a) molecules responsible for the fluorescence emission of photosystem I (PS I). The fluorescence spectra of single PS I complexes are dominated by several red-shifted Chl a molecules categorized into red pools called C708 and C719. By polarization dependent measurements we demonstrate spectrally separate emissions corresponding to C708 and C719 in single PS I monomers and trimers. Moreover, we compared the results of SMS polarization dependent between monomeric and trimeric PS I complexes and give an estimation for the orientation between these red pools. As a consequence, we get new insight into the energy transfer towards and between the red Chl a molecules in PS I complexes.

  19. Revisiting glutaraldehyde cross-linking: the case of the Arg–Lys intermolecular doublet

    International Nuclear Information System (INIS)

    A specific Lys–Arg cross-link is observed in trimeric barnase crystals. In addition to the common use of glutaraldehyde to nonspecifically cross-link protein crystals through lysine residues disposed on the surface of the protein, the use of gentle vapour diffusion of glutaraldehyde offers a convenient way to limit polymerization and to allow slow diffusion throughout the crystal. In the case of trimeric barnase crystals, a specific cross-link was observed between an lysine side chain and an arginine side chain that were spatially disposed at the ideal distance on the protein surface in the three monomers. Here, the direct observation of a specific Lys–Arg cross-link site is reported and a mechanism is proposed for the reaction

  20. Study on multimers and their structures in molecular association mixture

    Institute of Scientific and Technical Information of China (English)

    YAMAGUCHI; Yoshinori; OZAKI; Yukihiro

    2007-01-01

    Self-association system of(R)-1,3-butanediol in dilute carbon tetrachloride(CCl4)solution is studied as a model of molecular association mixture.Analysis methods including FSMWEFA(fixed-size moving window evolving factor analysis)combined with PCA(principal component analysis),SIMPLISMA (simple-to-use interactive self-modeling mixture analysis),and ITTFA(iterative target transformation factor analysis)are adopted to resolve infrared spectra of(R)-1,3-butanediol solution.Association number and equilibrium constant are computed.(R)-1,3-butanediol in dilute inert solution is determined as a monomer-trimer equilibrium system.Theoretical investigation of trimer structures is carried out with DFT(density functional theory),and structural factors are analyzed.

  1. Weak links between fast mobility and local structure in molecular and atomic liquids

    CERN Document Server

    Bernini, S; Leporini, D

    2016-01-01

    We investigate by Molecular-Dynamics simulations the fast mobility - the rattling amplitude of the particles temporarily trapped by the cage of the neighbors - in mildly supercooled states of dense molecular (linear trimers) and atomic (binary mixtures) liquids. The mixture particles interact by the Lennard-Jones potential. The non-bonded particles of the molecular system are coupled by the more general Mie potential with variable We investigate by Molecular-Dynamics simulations the fast mobility - the rattling amplitude of the particles temporarily trapped by the cage of the neighbors - in mildly supercooled states of dense molecular (linear trimers) and atomic (binary mixtures) liquids. The mixture particles interact by the Lennard-Jones potential. The non-bonded particles of the molecular system are coupled by the more general Mie potential with variable repulsive and attractive exponents in a range which is characteristic of small $n$-alkanes and $n$-alcohols. Possible links between the fast mobility and ...

  2. Nitrate-bridged "pseudo-double-propeller"-type lanthanide(III)-copper(II) heterometallic clusters: syntheses, structures, and magnetic properties.

    Science.gov (United States)

    Chaudhari, Abhijeet K; Joarder, Biplab; Rivière, Eric; Rogez, Guillaume; Ghosh, Sujit K

    2012-09-01

    Two discrete nitrate-bridged novel "pseudo-double-propeller"-shaped hexanuclear Cu/Ln clusters of the formula [Cu(4)Ln(2)L(4)L'(4)(NO(3))(2)(OH(2))(2)]·3NO(3)·4H(2)O [Ln = Dy, Gd; LH = o-vanilin; L'H = 2-(hydroxyethyl)pyridine] were synthesized and characterized. Single-crystal X-ray diffraction studies revealed the trimeric half-propeller-type Cu(2)/Ln core connected to other opposite-handed similar trimers by a bridging nitrate ligand. The Dy analogue, [Cu(4)Dy(2)L(4)L'(4)(NO(3))(2)(OH(2))(2)]·3NO(3)·4H(2)O, shows frequency-dependent out-of-phase alternating-current magnetic susceptibility, which indicates that this novel discrete [Cu(4)Dy(2)] heterometallic cluster may exhibit single-molecule-magnet behavior. PMID:22909388

  3. Structure of Rv1848 (UreA), the Mycobacterium tuberculosis urease γ subunit

    International Nuclear Information System (INIS)

    Crystal and solution structures of Rv1848 protein and their implications in the biological assembly of Mtb urease is presented. The crystal structure of the urease γ subunit (UreA) from Mycobacterium tuberculosis, Rv1848, has been determined at 1.8 Å resolution. The asymmetric unit contains three copies of Rv1848 arranged into a homotrimer that is similar to the UreA trimer in the structure of urease from Klebsiella aerogenes. Small-angle X-ray scattering experiments indicate that the Rv1848 protein also forms trimers in solution. The observed homotrimer and the organization of urease genes within the M. tuberculosis genome suggest that M. tuberculosis urease has the (αβγ)3 composition observed for other bacterial ureases. The γ subunit may be of primary importance for the formation of the urease quaternary structure

  4. Proposed experiment to study the critical ionization velocity theory in space

    International Nuclear Information System (INIS)

    A simple, novel experiment is suggested to verify the critical ionization hypothesis in space. The experiment involves the isentropic expansion of gas through a carefully chosen nozzle and skimmer so that the formation of dimers and trimers is enhanced. Because of the reduced ionization potentials of these species and because of the increased mass, it is expected that the critical ionization velocity will be lowered considerably even for simple gases such as N2. The release of the gas aboard the space shuttle, whose orbiting velocity is about 7.3 km s/sup -1/, will provide the necessary velocity relative to the ambient ions to ionize the dimers and trimers. The advantages of this method over previously tried or proposed methods are briefly discussed

  5. Pectinolytic bacteria and their secreted pectate lyases: agents for the maceration and solubilization of phytomass for fuels production

    Energy Technology Data Exchange (ETDEWEB)

    Preston, J.F. III; Rice, J.D.; Chow, M.C. (Florida Univ., Gainesville, FL (United States). Dept. of Microbiology and Cell Science)

    1993-01-01

    The objectives of this research have been to identify the pectinolytic enzymes secreted by bacteria and apply these towards the enhanced maceration and solubilization of plant material, focusing on the pectate lyases secreted by the phytopathogenic strains of Erwinia chrysanthemi, the ruminant resident Lachnospira multiparus, and the wood digestor isolate, Clostridium populeti. An HPLC approach has been developed that permits the kinetic analysis of each enzyme with respect to the formation of individual products during the pectate depolymerization process. This approach has demonstrated that each of these organisms secretes a nonrandom trimer-generating pectate lyase with a combination of endolytic and exolytic depolymerizing mechanisms. Two different strains of E. chrysanthemi secrete a battery of pectate lyases that include random endolytic as well as nonrandom dimer - and nonrandom trimer-generating endolytic/exolytic mechanisms. (author)

  6. A simplified laminin nomenclature

    DEFF Research Database (Denmark)

    Aumailley, Monique; Bruckner-Tudermann, Leena; Carter, William G.;

    2005-01-01

    A simplification of the laminin nomenclature is presented. Laminins are multidomain heterotrimers composed of alpha, beta and gamma chains. Previously, laminin trimers were numbered with Arabic numerals in the order discovered, that is laminins-1 to -5. We introduce a new identification system...... for a trimer using three Arabic numerals, based on the alpha, beta and gamma chain numbers. For example, the laminin with the chain composition alpha5beta1gamma1 is termed laminin-511, and not laminin-10. The current practice is also to mix two overlapping domain and module nomenclatures. Instead of the older...... Roman numeral nomenclature and mixed nomenclature, all modules are now called domains. Some domains are renamed or renumbered. Laminin epidermal growth factor-like (LE) domains are renumbered starting at the N-termini, to be consistent with general protein nomenclature. Domain IVb of alpha chains...

  7. Thermal Entanglement and Critical Behavior of Magnetic Properties on a Triangulated Kagomé Lattice

    Directory of Open Access Journals (Sweden)

    N. Ananikian

    2011-01-01

    Full Text Available The equilibrium magnetic and entanglement properties in a spin-1/2 Ising-Heisenberg model on a triangulated Kagomé lattice are analyzed by means of the effective field for the Gibbs-Bogoliubov inequality. The calculation is reduced to decoupled individual (clusters trimers due to the separable character of the Ising-type exchange interactions between the Heisenberg trimers. The concurrence in terms of the three qubit isotropic Heisenberg model in the effective Ising field in the absence of a magnetic field is non-zero. The magnetic and entanglement properties exhibit common (plateau, peak features driven by a magnetic field and (antiferromagnetic exchange interaction. The (quantum entangled and non-entangled phases can be exploited as a useful tool for signalling the quantum phase transitions and crossovers at finite temperatures. The critical temperature of order-disorder coincides with the threshold temperature of thermal entanglement.

  8. Reversible peptide oligomerization over nanoscale gold surfaces

    Directory of Open Access Journals (Sweden)

    Kazushige Yokoyama

    2015-11-01

    Full Text Available A selective oligomeric formation of amyloid beta 1-40 (Ab1-40 monomers over a nanogold colloidal surface was investigated. An unfolded Ab1-40 monomer is considered to construct a dimer or trimer based oligomeric form with its hydrophobic segment placing outward under an acidic condition. Under a basic condition, a conformation of Ab is expected to take a folded monomeric form with its hydrophilic segment folded inward, avoiding the networking with residual colloidal particles. The most probable oligomeric form constructed over a 20 nm gold colloidal surface within a 25 ℃ to 65 ℃ temperature range is a dimer based unit and that over 30 or 40 nm gold colloidal surface below 15 ℃ is concluded to be a trimer based unit. However, selective oligomerization was not successfully reproduced under the rest of the conditions. A dipole-induced dipole interaction must cause a flexible structural change between folded and unfolded forms.

  9. Capsid-like Arrays in Crystals of Chimpanzee Adenovirus Hexon

    International Nuclear Information System (INIS)

    The major coat protein, hexon, from a chimpanzee adenovirus (AdC68) is of interest as a target for vaccine vector modification. AdC68 hexon has been crystallized in the orthorhombic space group C222 with unit cell dimensions of a = 90.8 Angstroms, b = 433.0 Angstroms, c = 159.3 Angstroms, and one trimer (3 x 104,942 Da) in the asymmetric unit. The crystals diffract to 2.1 Angstroms resolution. Initial studies reveal that the molecular arrangement is quite unlike that in hexon crystals for human adenovirus. In the AdC68 crystals, hexon trimers are parallel and pack closely in two-dimensional continuous arrays similar to those formed on electron microscope grids. The AdC68 crystals are the first in which adenovirus hexon has molecular interactions that mimic those used in constructing the viral capsid

  10. Cooperative enhancement versus additivity of two-photon-absorption cross sections in linear and branched squaraine superchromophores.

    Science.gov (United States)

    Ceymann, Harald; Rosspeintner, Arnulf; Schreck, Maximilian H; Mützel, Carina; Stoy, Andreas; Vauthey, Eric; Lambert, Christoph

    2016-06-28

    The linear and nonlinear optical properties of a series of oligomeric squaraine dyes were investigated by one-photon absorption spectroscopy (1PA) and two-photon absorption (2PA) induced fluorescence spectroscopy. The superchromophores are based on two indolenine squaraine dyes with transoid (SQA) and cisoid configuration (SQB). Using these monomers, linear dimers and trimers as well as star-shaped trimers and hexamers with benzene or triphenylamine cores were synthesised and investigated. The red-shifted and intensified 1PA spectra of all superchromophores could well be explained by exciton coupling theory. In the linear chromophore arrangements we also found superradiance of fluorescence but not in the branched systems. Furthermore, the 2PA showed enhanced cross sections for the linear oligomers but only additivity for the branched systems. This emphasizes that the enhancement of the 2PA cross section in the linear arrangements is probably caused by orbital interactions of higher excited configurations. PMID:27264847

  11. Impurity in a Bose-Einstein Condensate and the Efimov Effect.

    Science.gov (United States)

    Levinsen, Jesper; Parish, Meera M; Bruun, Georg M

    2015-09-18

    We investigate the zero-temperature properties of an impurity particle interacting with a Bose-Einstein condensate (BEC), using a variational wave function that includes up to two Bogoliubov excitations of the BEC. This allows one to capture three-body Efimov physics, as well as to recover the first nontrivial terms in the weak-coupling expansion. We show that the energy and quasiparticle residue of the dressed impurity (polaron) are significantly lowered by three-body correlations, even for weak interactions where there is no Efimov trimer state in a vacuum. For increasing attraction between the impurity and the BEC, we observe a smooth crossover from atom to Efimov trimer, with a superposition of states near the Efimov resonance. We furthermore demonstrate that three-body loss does not prohibit the experimental observation of these effects. Our results thus suggest a route to realizing Efimov physics in a stable quantum many-body system for the first time. PMID:26430999

  12. A 2:1 receptor/C60 complex as a nanosized universal joint.

    Science.gov (United States)

    Yanney, Michael; Fronczek, Frank R; Sygula, Andrzej

    2015-09-14

    Buckycatcher II, a C51 H24 hydrocarbon with two corannulene pincers on a dibenzonorbornadiene tether, exhibits an affinity toward C60 in organic solvents that is dramatically higher than the original buckycatcher C60 H28 and other corannulene-based molecular receptors for fullerenes. In addition to the formation of an usual 1:1 C60 @catcher inclusion complex, a trimeric C60 @(catcher)2 assembly is detected in solutions and in the solid state. X-ray structure determination reveals a remarkable "universal joint" solvent-free crystal arrangement of the trimer, with a single fullerene cage wrapped by four corannulene subunits of two cooperating catcher receptors. PMID:26352025

  13. The procollagen N-proteinases ADAMTS2, 3 and 14 in pathophysiology.

    Science.gov (United States)

    Bekhouche, Mourad; Colige, Alain

    2015-01-01

    Collagen fibers are the main components of most of the extracellular matrices where they provide a structural support to cells, tissues and organs. Fibril-forming procollagens are synthetized as individual chains that associate to form homo- or hetero-trimers. They are characterized by the presence of a central triple helical domain flanked by amino and carboxy propeptides. Although there are some exceptions, these two propeptides have to be proteolytically removed to allow the almost spontaneous assembly of the trimers into collagen fibrils and fibers. While the carboxy-propeptide is mainly cleaved by proteinases from the tolloid family, the amino-propeptide is usually processed by procollagen N-proteinases: ADAMTS2, 3 and 14. This review summarizes the current knowledge concerning this subfamily of ADAMTS enzymes and discusses their potential involvement in physiopathological processes that are not directly linked to fibrillar procollagen processing. PMID:25863161

  14. Stability of a melittin pore in a lipid bilayer a molecular dynamics study

    OpenAIRE

    Lin, J -H; Baumgärtner, A

    2000-01-01

    We have investigated the configuration and the stability of a single membrane pore bound by four melittin molecules and embedded in a fully hydrated bilayer lipid membrane. We used molecular dynamics simulations up to 5.8 ns. It is found that the initial tetrameric configuration decays with increasing time into a stable trimer and one monomer. This continuous transformation is accompanied by a lateral expansion of the aqueous pore exhibiting a final size comparable to experimental findings. T...

  15. Incorporation of Cofilin into Rods Depends on Disulfide Intermolecular Bonds: Implications for Actin Regulation and Neurodegenerative Disease

    OpenAIRE

    Bernstein, Barbara W; Alisa E Shaw; Minamide, Laurie S.; Pak, Chi W.; Bamburg, James R.

    2012-01-01

    Rod-shaped aggregates (“rods”), containing equimolar actin and the actin dynamizing protein cofilin, appear in neurons following a wide variety of potentially oxidative stress: simulated microischemia, cofilin overexpression, and exposure to peroxide, excess glutamate, or the dimer/trimer forms of amyloid-β peptide (Aβd/t), the most synaptotoxic Aβ species. These rods are initially reversible and neuroprotective, but if they persist in neurites, the synapses degenerate without neurons dying. ...

  16. Poly(ADP-ribose) synthesis, a marker of granulocyte differentiation.

    OpenAIRE

    Ikai, K; Ueda, K; Fukushima, M.; Nakamura, T.; Hayaishi, O

    1980-01-01

    By using an indirect immunofluorescence technique, the distribution of poly(ADP-ribose) synthesis in human blood cells was investigated. The antibody used was reactive with poly(ADP-ribose) larger than trimers. The specific immunofluorescence of poly(ADP-ribose) synthesized in situ from NAD+ was observed in nuclei of lymphocytes and monocytes in normal peripheral blood. No immunofluorescence, however, was detected in granulocytes and erythrocytes. In agreement with this finding, no incorporat...

  17. Bone-seeking TRAP conjugates: surprising observations and their implications on the development of gallium-68-labeled bisphosphonates

    OpenAIRE

    Notni, Johannes; Plutnar, Jan; Wester, Hans-Jürgen

    2012-01-01

    Background Bisphosphonates possess strong affinity to bone. 99mTc bisphosphonate complexes are widely used for bone scintigraphy. For positron emission tomography (PET) bone imaging, Ga-68-based PET tracers based on bisphosphonates are highly desirable. Findings Two trimeric bisphosphonate conjugates of the triazacyclononane-phosphinate (TRAP) chelator were synthesized, labeled with Ga-68, and used for microPET imaging of bone in male Lewis rats. Both Ga-68 tracers show bone uptake and, thus,...

  18. Antioxidant Tannins from Stem Bark and Fine Root of Casuarina equisetifolia

    OpenAIRE

    Guang-Hui Lin; Shu-Dong Wei; Hai-Chao Zhou; Yi-Ming Lin; Shang-Ju Zhang; Gong-Fu Ye

    2010-01-01

    Structures of condensed tannins from the stem bark and fine root of Casuarina equisetifolia were identified using MALDI-TOF MS and HPLC analyses. The condensed tannins from stem bark and fine root consist predominantly of procyanidin combined with prodelphinidin and propelargonidin, and epicatechin is the main extension unit. The condensed tannins had different polymer chain lengths, varying from trimers to tridecamer for stem bark and to pentadecamer for fine root. The antioxidant activities...

  19. Membrane glycoprotein folding, oligomerization and intracellular transport: effects of dithiothreitol in living cells

    OpenAIRE

    Braakman, L.J.; Tatu, U.; Helenius, A

    1993-01-01

    Using influenza hemagglutinin (HA0) and vesicular stomatitis virus G protein as model proteins, we have analyzed the effects of dithiothreitol (DTT) on conformational maturation and transport of glycoproteins in the secretory pathway of living cells. While DTT caused reduction of folding intermediates and misfolded proteins in the endoplasmic reticulum (ER), it did not affect molecules that had already acquired a mature trimeric conformation, whether present in the ER or elsewhere. The conver...

  20. Solvothermal indium fluoride chemistry: Syntheses and crystal structures of K 5In 3F 14, β-(NH 4) 3InF 6 and [NH 4] 3[C 6H 21N 4] 2[In 4F 21

    Science.gov (United States)

    Jayasundera, Anil C. A.; Goff, Richard J.; Li, Yang; Finch, Adrian A.; Lightfoot, Philip

    2010-02-01

    The solvothermal syntheses and crystal structures of three indium fluorides are presented. K 5In 3F 14 ( 1) and β-(NH 4) 3InF 6 ( 2) are variants on known inorganic structure types chiolite and cryolite, respectively, with the latter exhibiting a complex and apparently novel structural distortion. [NH 4] 3[C 6H 21N 4] 2[In 4F 21] ( 3) represents a new hybrid composition displaying a unique trimeric metal fluoride building unit.

  1. Relationship between SU Subdomains That Regulate the Receptor-Mediated Transition from the Native (Fusion-Inhibited) to the Fusion-Active Conformation of the Murine Leukemia Virus Glycoprotein

    OpenAIRE

    Lavillette, Dimitri; Ruggieri, Alessia; Boson, Bertrand; Maurice, Marielle; Cosset, François-Loïc

    2002-01-01

    Envelope glycoproteins (Env) of retroviruses are trimers of SU (surface) and TM (transmembrane) heterodimers and are expressed on virions in fusion-competent forms that are likely to be metastable. Activation of the viral receptor-binding domain (RBD) via its interaction with a cell surface receptor is thought to initiate a cascade of events that lead to refolding of the Env glycoprotein into its stable fusion-active conformation. While the fusion-active conformation of the TM subunit has bee...

  2. Investigation of structural change of purple membrane in storage by transmission electron microscope and atomic force microscope

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The structural change of purple membrane during storage has been investigated by means of transmission electron microscope and atomic force microscope. It is found that many liposomes have spontaneously evolved from the purple membrane sheets isolated three years ago. The membrane proteins on the liposomes, bacteriorhodopsin, are still presented as trimers in 2-D hexagonal structure, which is the same as that in natural cell membrane. However, the cytoplasmic surface of purple membrane faced outside on the liposomes.

  3. Identification of the UDP-N-Acetylglucosamine 4-Epimerase Involved in Exosporium Protein Glycosylation in Bacillus anthracis▿

    OpenAIRE

    Dong, Shengli; Chesnokova, Olga N.; Turnbough, Charles L.; Pritchard, David G.

    2009-01-01

    Spores of Bacillus anthracis, the causative agent of anthrax, are enclosed by a loosely fitting exosporium composed of a basal layer and an external hair-like nap. The filaments of the nap are formed by trimers of the collagen-like glycoprotein BclA. The side chains of BclA include multiple copies of two linear rhamnose-containing oligosaccharides, a trisaccharide and a pentasaccharide. The pentasaccharide terminates with the unusual deoxyamino sugar anthrose. Both oligosaccharide side chains...

  4. Thermal quenching of electronic shells and channel competition in cluster fission

    OpenAIRE

    Yannouleas, Constantine; Landman, Uzi; Brechignac, C.; Cahuzac, Ph.; Concina, B.; Leygnier, J.

    2002-01-01

    Experimental and theoretical studies of fission of doubly-charged Li, Na, and K clusters in the low fissility regime reveal the strong influence of electronic shell effects on the fission products. The electronic entropy controls the quenching of the shell effects and the competition between magic-fragment channels, leading to a transition from favored channels of higher mass symmetry to the asymmetric channel involving the trimer cation at elevated temperatures.

  5. Oxidation of α-lactalbumin peptides with and without procyanidins

    OpenAIRE

    Zeng, Xin

    2014-01-01

    The literature review part describes a whey protein, α-lactalbumin (ALA) and its oxidation, aronia (Aronia melanocarpa) procyanidins including their chemistry and analysis, as well as interactions between protein and plant phenolics. The aim of the thesis was to study the oxidation of tryptic peptides of ALA with and without procyanidins. Fractions containing both procyanidin dimers and trimers were collected from aronia juice proanthocyanidins with preparative-HPLC thereafter identifie...

  6. Stabilization of HIV-1 gp120-CD4 Receptor Complex through Targeted Interchain Disulfide Exchange*

    OpenAIRE

    Cerutti, Nichole; Mendelow, Barry V.; Napier, Grant B.; Papathanasopoulos, Maria A.; Killick, Mark; Khati, Makobetsa; Stevens, Wendy; Capovilla, Alexio

    2010-01-01

    HIV-1 enters cells via interaction between the trimeric envelope (Env) glycoprotein gp120/gp41 and the host cell surface receptor molecule CD4. The requirement of CD4 for viral entry has rationalized the development of recombinant CD4-based proteins as competitive viral attachment inhibitors and immunotherapeutic agents. In this study, we describe a novel recombinant CD4 protein designed to bind gp120 through a targeted disulfide-exchange mechanism. According to structural models of the gp120...

  7. The Ability of Multimerized Cyclophilin A to Restrict Retrovirus Infection

    OpenAIRE

    Javanbakht, Hassan; Diaz-Griffero, Felipe; Yuan, Wen; Yeung, Darwin F.; Li, Xing; Song, Byeongwoon; Sodroski, Joseph

    2007-01-01

    In owl monkeys, the typical retroviral restriction factor of primates, TRIM5α, is replaced by TRIMCyp. TRIMCyp consists of the TRIM5 RING, B-box 2 and coiled-coil domains, as well as the intervening linker regions, fused with cyclophilin A. TRIMCyp restricts infection of retroviruses, such as human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV), with capsids that can bind cyclophilin A. The TRIM5 coiled coil promotes the trimerization of TRIMCyp. Here we show that cycl...

  8. Fiber knob domain lacking the shaft sequence but fused to a coiled coil is a candidate subunit vaccine against egg-drop syndrome.

    Science.gov (United States)

    Harakuni, Tetsuya; Andoh, Kiyohiko; Sakamoto, Ryu-Ichi; Tamaki, Yukihiro; Miyata, Takeshi; Uefuji, Hirotaka; Yamazaki, Ken-Ichi; Arakawa, Takeshi

    2016-06-01

    Egg-drop syndrome (EDS) virus is an avian adenovirus that causes a sudden drop in egg production and in the quality of the eggs when it infects chickens, leading to substantial economic losses in the poultry industry. Inactivated EDS vaccines produced in embryonated duck eggs or cell culture systems are available for the prophylaxis of EDS. However, recombinant subunit vaccines that are efficacious and inexpensive are a desirable alternative. In this study, we engineered chimeric fusion proteins in which the trimeric fiber knob domain lacking the triple β-spiral motif in the fiber shaft region was genetically fused to trimeric coiled coils, such as those of the engineered form of the GCN4 leucine zipper peptide or chicken cartilage matrix protein (CMP). The fusion proteins were expressed predominantly as soluble trimeric proteins in Escherichia coli at levels of 15-80mg/L of bacterial culture. The single immunization of chickens with the purified fusion proteins, at a dose equivalent to 10μg of the knob moiety, elicited serum antibodies with high hemagglutination inhibition (HI) activities, similar to those induced by an inactivated EDS vaccine. A dose-response analysis indicated that a single immunization with as little as 1μg of the knob moiety of the CMP-knob fusion protein was as effective as the inactivated vaccine in inducing antibodies with HI activity. The immunization of laying hens had no apparent adverse effects on egg production and effectively prevented clinical symptoms of EDS when the chickens were challenged with pathogenic EDS virus. This study demonstrates that the knob domain lacking the shaft sequence but fused to a trimeric coiled coil is a promising candidate subunit vaccine for the prophylaxis of EDS in chickens. PMID:27105561

  9. Oligomerization of Fusogenic Peptides Promotes Membrane Fusion by Enhancing Membrane Destabilization

    OpenAIRE

    Lau, Wai Leung; Ege, David S.; Lear, James D.; Hammer, Daniel A.; DeGrado, William F.

    2004-01-01

    A key element of membrane fusion reactions in biology is the involvement of specific fusion proteins. In many viruses, the proteins that mediate membrane fusion usually exist as homotrimers. Furthermore, they contain extended triple-helical coiled-coil domains and fusogenic peptides. It has been suggested that the coiled-coil domains present the fusogenic peptide in a conformation or geometry favorable for membrane fusion. To test the hypothesis that trimerization of fusogenic peptide is rela...

  10. Broad-Spectrum Inhibition of HIV-1 by a Monoclonal Antibody Directed against a gp120-Induced Epitope of CD4

    OpenAIRE

    Burastero, Samuele E.; Frigerio, Barbara; Lopalco, Lucia; Sironi, Francesca; Breda, Daniela; Longhi, Renato; Scarlatti, Gabriella; Canevari, Silvana; Figini, Mariangela; Lusso, Paolo

    2011-01-01

    To penetrate susceptible cells, HIV-1 sequentially interacts with two highly conserved cellular receptors, CD4 and a chemokine receptor like CCR5 or CXCR4. Monoclonal antibodies (MAbs) directed against such receptors are currently under clinical investigation as potential preventive or therapeutic agents. We immunized Balb/c mice with molecular complexes of the native, trimeric HIV-1 envelope (Env) bound to a soluble form of the human CD4 receptor. Sera from immunized mice were found to conta...

  11. PCNA Damage Caused by Anti-Neoplastic Drugs

    OpenAIRE

    Bae, Soo In; Zhao,Ran; Snapka, Robert M.

    2008-01-01

    Structurally diverse chemotherapeutic and chemopreventive drugs, including camptothecin, doxorubicin, sanguinarine, and others, were found to cause covalent crosslinking of proliferating cell nuclear antigen (PCNA) trimers in mammalian cells exposed to fluorescent light. This PCNA damage was caused by both nuclear and cytoplasmically localizing drugs. For some drugs, the PCNA crosslinking was evident even with very brief exposures to laboratory room lighting. In the absence of drugs, there wa...

  12. Signal Transduction Pathways Leading to Heat Shock Transcription

    OpenAIRE

    Calderwood, S K; Xie, Y.; X. Wang; Khaleque, M. A.; Chou, S. D.; Murshid, A.; Prince, T.; Zhang, Y.

    2010-01-01

    Heat shock proteins (HSP) are essential for intracellular protein folding during stress and protect cells from denaturation and aggregation cascades that can lead to cell death. HSP genes are regulated at the transcriptional level by heat shock transcription factor 1 (HSF1) that is activated by stress and binds to heat shock elements in HSP genes. The activation of HSF1 during heat shock involves conversion from an inert monomer to a DNA binding trimer through a series of intramolecular foldi...

  13. Rabbits immunized with Epstein-Barr virus gH/gL or gB recombinant proteins elicit higher serum virus neutralizing activity than gp350.

    Science.gov (United States)

    Cui, Xinle; Cao, Zhouhong; Chen, Quanyi; Arjunaraja, Swadhinya; Snow, Andrew L; Snapper, Clifford M

    2016-07-25

    Epstein-Barr virus (EBV) is the primary cause of infectious mononucleosis and has been strongly implicated in the etiology of multiple epithelial and lymphoid cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin lymphoma, Burkitt lymphoma, non-Hodgkin lymphoma and post-transplant lymphoproliferative disorder. There is currently no licensed prophylactic vaccine for EBV. Most efforts to develop prophylactic vaccines have focused on EBV gp350, which binds to CD21/CD35 to gain entry into B cells, and is a major target of serum neutralizing antibody in EBV seropositive humans. However, a recombinant monomeric gp350 protein failed to prevent EBV infection in a phase II clinical trial. Thus, alternative or additional target antigens may be necessary for a successful prophylactic vaccine. EBV gH/gL and gB proteins coordinately mediate EBV fusion and entry into B cells and epithelial cells, strongly suggesting that vaccination with these proteins might elicit antibodies that will prevent EBV infection. We produced recombinant trimeric and monomeric EBV gH/gL heterodimeric proteins and a trimeric EBV gB protein, in addition to tetrameric and monomeric gp350(1-470) proteins, in Chinese hamster ovary cells. We demonstrated that vaccination of rabbits with trimeric and monomeric gH/gL, trimeric gB, and tetrameric gp350(1-470) induced serum EBV-neutralizing titers, using cultured human B cells, that were >100-fold, 20-fold, 18-fold, and 4-fold higher, respectively, than monomeric gp350(1-470). These data strongly suggest a role for testing EBV gH/gL and EBV gB in a future prophylactic vaccine to prevent EBV infection of B cells, as well as epithelial cells. PMID:27291087

  14. Cooperative long range protein-protein dynamics in Purple Membrane

    OpenAIRE

    Rheinstadter, Maikel; Schmalzl, Karin; Wood, Kathleen; Strauch, Dieter

    2008-01-01

    We present experimental evidence for a long-range protein-protein interaction in purple membrane (PM). The interprotein dynamics were quantified by measuring the spectrum of the acoustic phonons in the 2D bacteriorhodopsin (BR) protein lattice using inelastic neutron scattering. Phonon energies of about 1 meV were determined. The data are compared to an analytical model, and the effective spring constant for the interaction between neighboring protein trimers are determined to be k=53 N/m. Ad...

  15. New Proposal of Setal Homology in Schizomida and Revision of Surazomus (Hubbardiidae) from Ecuador

    OpenAIRE

    Osvaldo Villarreal Manzanilla; Gustavo Silva de Miranda; Alessandro Ponce de Leão Giupponi

    2016-01-01

    The homology of three somatic systems in Schizomida is studied yielding the following results: (1) proposal of homology and chaetotaxy of abdominal setae in Surazomus; (2) revision of the cheliceral chaetotaxy in Schizomida, with suggestion of new homology scheme between Hubbardiidae and Protoschizomidae, description of a new group of setae in Hubbardiinae (G7), and division of setae group 5 in two subgroups, G5A and G5B; (3) proposal of segmental homology between trimerous and tetramerous fe...

  16. Dimer-atom-atom recombination in the universal four-boson system

    OpenAIRE

    Deltuva, A.

    2012-01-01

    The dimer-atom-atom recombination process in the system of four identical bosons with resonant interactions is studied. The description uses the exact Alt, Grassberger and Sandhas equations for the four-particle transition operators that are solved in the momentum-space framework. The dimer-dimer and atom-trimer channel contributions to the ultracold dimer-atom-atom recombination rate are calculated. The dimer-atom-atom recombination rate greatly exceeds the three-atom recombination rate.

  17. Influence of Peptide Ligand Surface Density and Ethylene Oxide Spacer Arm on the Capture of Porcine Parvovirus

    OpenAIRE

    Heldt, Caryn L.; Gurgel, Patrick V.; Jaykus, Lee-Ann; Carbonell, Ruben G.

    2009-01-01

    In previous work, we identified two trimeric peptide ligands (designated WRW and KYY) which bound specifically to porcine parvovirus (PPV) and demonstrated their ability to capture and remove the virus from solutions containing 7.5% human blood plasma. This paper examines the influences of peptide density and the presence of an ethylene oxide spacer arm on the efficiency of virus capture using these two ligands. The WRW peptide bound the most virus from plasma solutions at the lowest peptide ...

  18. Synthesis and Characterization of Polyesteramide Hot Melt Adhesive from Low Purity Dimer Acid, Ethylenediamine, and Ethanolamine

    OpenAIRE

    Pravin G. KADAM; Vaidya, Parth; Mhaske, Shashank T.

    2014-01-01

    Polyesteramide hot melt adhesive (HMA) was synthesized using low purity dimer acid (composition: 3% linoleic acid, 75% dimer acid, and 22% trimer acid), ethanolamine, and ethylenediamine. Ethanolamine was added as a partial replacement (10, 20, and 30%) of ethylenediamine. Prepared HMAs were characterized for acid value, amine value, hydroxyl value, Fourier transform infrared spectroscopy, mechanical (tensile strength, percentage strain at brea, and shore D hardness), thermal (glass transitio...

  19. Reactions of strained hydrocarbons with alkene and alkyne metathesis catalysts.

    Science.gov (United States)

    Carnes, Matthew; Buccella, Daniela; Siegrist, Theo; Steigerwald, Michael L; Nuckolls, Colin

    2008-10-29

    Here we describe the metathesis reactions of a strained eight-membered ring that contains both alkene and alkyne functionality. We find that the alkyne metathesis catalyst produces polymer through a ring-opening alkyne metathesis reaction that is driven by the strain release from the monomer. The strained monomer provides unusual reactivity with ruthenium-based alkene metathesis catalysts. We isolate a discrete trimeric species a Dewar benzene derivative that is locked in this form through an unsaturated cyclophane strap. PMID:18826219

  20. Design of co-crystals/salts of some Nitrogenous bases and some derivatives of thiophene carboxylic acids through a combination of hydrogen and halogen bonds

    OpenAIRE

    Jennifer, Samson Jegan; Muthiah, Packianathan Thomas

    2014-01-01

    Background The utility of N-heterocyclic bases to obtain molecular complexes with carboxylic acids is well studied. Depending on the solid state interaction between the N-heterocyclic base and a carboxylic acid a variety of neutral or ionic synthons are observed. Meanwhile, pyridines and pyrimidines have been frequently chosen in the area of crystal engineering for their multipurpose functionality. HT (hetero trimers) and LHT (linear heterotetramers) are the well known synthons that are forme...

  1. N-annulated perylene fused porphyrins with enhanced near-IR absorption and emission

    KAUST Repository

    Jiao, Chongjun

    2010-09-17

    N-Annulated perylene fused porphyrins 1 and 2 were synthesized by oxidative dehydrogenation using a Sc(OTf)3/DDQ system. These newly synthesized hybrid molecules are highly soluble in organic solvents and exhibit remarkably intense near-IR absorption, as well as detectable photoluminescence quantum yields, all of which are comparable to or even exceed those of either meso-β doubly linked porphyrin dimer/trimer or bis/tri-N-annulated rylenes. © 2010 American Chemical Society.

  2. Identification of a Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Variant Resistant to Cold Inactivation▿ †

    OpenAIRE

    Kassa, Aemro; Finzi, Andrés; Pancera, Marie; Courter, Joel R.; Amos B Smith; Sodroski, Joseph

    2009-01-01

    The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein trimer consists of gp120 and gp41 subunits and undergoes a series of conformational changes upon binding to the receptors, CD4 and CCR5/CXCR4, that promote virus entry. Surprisingly, we found that the envelope glycoproteins of some HIV-1 strains are functionally inactivated by prolonged incubation on ice. Serial exposure of HIV-1 to extremes of temperature, followed by expansion of replication-competent viruses, allowed sel...

  3. Photoassociation of a cold atom-molecule pair: long-range quadrupole-quadrupole interactions

    OpenAIRE

    Lepers, M.; Dulieu, O.; Kokoouline, V.

    2010-01-01

    The general formalism of the multipolar expansion of electrostatic interactions is applied to the calculation the potential energy between an excited atom (without fine structure) and a ground state diatomic molecule at large separations. Both partners exhibit a permanent quadrupole moment, so that their mutual quadrupole-quadrupole long-range interaction is attractive enough to bind trimers. Numerical results are given for an excited Cs(6P) atom and a ground state Cs2 molecule. The prospects...

  4. Crystallization and preliminary X-ray analysis of Chandipura virus glycoprotein G

    International Nuclear Information System (INIS)

    Chandipura virus glycoprotein ectodomain (Gth) was purified and crystallized at pH 7.5. X-ray diffraction data set was collected to a resolution of 3.1 Å. Fusion in members of the Rhabdoviridae virus family is mediated by the G glycoprotein. At low pH, the G glycoprotein catalyzes fusion between viral and endosomal membranes by undergoing a major conformational change from a pre-fusion trimer to a post-fusion trimer. The structure of the G glycoprotein from vesicular stomatitis virus (VSV G), the prototype of Vesiculovirus, has recently been solved in its trimeric pre-fusion and post-fusion conformations; however, little is known about the structural details of the transition. In this work, a soluble form of the ectodomain of Chandipura virus G glycoprotein (CHAV Gth) was purified using limited proteolysis of purified virus; this soluble ectodomain was also crystallized. This protein shares 41% amino-acid identity with VSV G and thus its structure could provide further clues about the structural transition of rhabdoviral glycoproteins induced by low pH. Crystals of CHAV Gth obtained at pH 7.5 diffracted X-rays to 3.1 Å resolution. These crystals belonged to the orthorhombic space group P21212, with unit-cell parameters a = 150.3, b = 228.2, c = 78.8 Å. Preliminary analysis of the data based on the space group and the self-rotation function indicated that there was no trimeric association of the protomers. This unusual oligomeric status could result from the presence of fusion intermediates in the crystal

  5. Mechanism for pH-dependent gene regulation by amino-terminus-mediated homooligomerization of Bacillus subtilis anti-trp RNA-binding attenuation protein

    OpenAIRE

    Sachleben, Joseph R.; McElroy, Craig A.; Gollnick, Paul; Foster, Mark P.

    2010-01-01

    Anti-TRAP (AT) is a small zinc-binding protein that regulates tryptophan biosynthesis in Bacillus subtilis by binding to tryptophan-bound trp RNA-binding attenuation protein (TRAP), thereby preventing it from binding RNA, and allowing transcription and translation of the trpEDCFBA operon. Crystallographic and sedimentation studies have shown that AT can homooligomerize to form a dodecamer, AT12, composed of a tetramer of trimers, AT3. Structural and biochemical studies suggest that only trime...

  6. Optical constants and self-assembly of phenylene ethynylene oligomer monolayers

    DEFF Research Database (Denmark)

    Marx, E.; Walzer, Karsten; Less, R.J.; Raithby, P.R.; Stokbro, Kurt; Greenham, N.C.

    2004-01-01

    This paper studies the self-assembly on gold surfaces of 1,4-ethynylphenyl-4'-ethynylphenyl-2'-nitro-1-benzenedithiolate (EP2NO(2)), a substituted phenylene ethynylene trimer with applications in molecular electronics. We develop an ellipsometric technique to measure the optical constants of thes...... self-assembled monolayers, and we also use attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and scanning tunneling microscopy (STM) to confirm the structure of the films....

  7. Antiherpetic activity of a flavonoid fraction from Ocotea notata leaves

    OpenAIRE

    Rafael Garrett; Maria Teresa V. Romanos; Ricardo M. Borges; MARCELO G. SANTOS; Leandro Rocha; Antonio Jorge R. da Silva

    2012-01-01

    This study describes the isolation of a flavonoid fraction from leaves of Ocotea notata (Nees & Mart.) Mez, Lauraceae, the identification of six major compounds (an A-type proanthocyanidin trimer [3], isoquercitrin [4], reynoutrin [5], miquelianin [6], quercitrin [7], afzelin [8]) and four minor compounds (catechin [1], epicatechin [2], quercetin [9], kaempferol [10]) present in the fraction and its activity against the Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). The 50% effective...

  8. Changing the Magnetic Configurations of Nanoclusters Atom-by-Atom

    OpenAIRE

    Lounis, Samir; Mavropoulos, Phivos; Zeller, Rudolf; Dederichs, Peter H.; Blügel, Stefan

    2006-01-01

    The Korringa-Kohn-Rostoker Green (KKR) function method for non-collinear magnetic structures was applied on Mn and Cr ad-clusters deposited on the Ni(111) surface. By considering various dimers, trimers and tetramers, a large amount of collinear and non-collinear magnetic structures is obtained. Typically all compact clusters have very small total moments, while the more open structures exhibit sizeable total moments, which is a result of the complex frustration mechanism in these systems. Th...

  9. Effect of local environment in resonant domains of polydisperse plasmonic nanoparticle aggregates on optodynamic processes in pulsed laser fields

    Institute of Scientific and Technical Information of China (English)

    A. E. Ershov; A. P. Gavrilyuk; S. V. Karpov; P. N. Semina

    2015-01-01

    Interactions of pulsed laser radiation with resonance domains of multiparticle colloidal aggregates having an increas-ingly complex local environment are studied via an optodynamic model. The model is applied to the simplest configurations, such as single particles, dimers, and trimers consisting of mono-and polydisperse Ag nanoparticles. We analyze how the local environment and the associated local field enhancement by surrounding particles affect the optodynamic processes in domains, including their photomodification and optical properties.

  10. Differential Form of the Skornyakov--Ter-Martirosyan Equations

    OpenAIRE

    Pen'kov, F. M.; Sandhas, W.

    2005-01-01

    The Skornyakov--Ter-Martirosyan three-boson integral equations in momentum space are transformed into differential equations. This allows us to take into account quite directly the Danilov condition providing self-adjointness of the underlying three-body Hamiltonian with zero-range pair interactions. For the helium trimer the numerical solutions of the resulting differential equations are compared with those of the Faddeev-type AGS equations.

  11. Differential form of the Skornyakov-Ter-Martirosyan Equations

    International Nuclear Information System (INIS)

    The Skornyakov-Ter-Martirosyan three-boson integral equations in momentum space are transformed into differential equations. This allows us to take into account quite directly the Danilov condition providing self-adjointness of the underlying three-body Hamiltonian with zero-range pair interactions. For the helium trimer the numerical solutions of the resulting differential equations are compared with those of the Faddeev-type AGS equations

  12. Differential form of the Skornyakov-Ter-Martirosyan Equations

    Science.gov (United States)

    Pen'Kov, F. M.; Sandhas, W.

    2005-12-01

    The Skornyakov-Ter-Martirosyan three-boson integral equations in momentum space are transformed into differential equations. This allows us to take into account quite directly the Danilov condition providing self-adjointness of the underlying three-body Hamiltonian with zero-range pair interactions. For the helium trimer the numerical solutions of the resulting differential equations are compared with those of the Faddeev-type AGS equations.

  13. Ring and Volcano Structures Formed by a Metal Dipyrromethene Complex

    Energy Technology Data Exchange (ETDEWEB)

    Son, Seung Bae; Hahn, Jae Ryang [Chonbuk National Univ., Jeonju (Korea, Republic of); Miao, Qing; Shin, Jiyoung; Dolphin, David [Univ. of British Columbia, Columbia (Canada)

    2014-06-15

    Dichloromethane liquid droplets containing a cobalt dipyrromethene trimer deposited on a graphite surface were found to form coffee ring, toroid ring, or volcano dot structures due to the redistribution of the solute during solvent evaporation. The shapes and size distributions of the ring structures depended on the drying temperature. The shape differences were attributed to the fact that the solvent evaporation rate controlled the self-assembly process that yielded the coffee stain and pinhole structures.

  14. Spectroscopic Study of the CP43′ Complex and the PSI–CP43′ Supercomplex of the Cyanobacterium Synechocystis PCC 6803

    OpenAIRE

    Feng, Ximao; Neupane, Bhanu; Acharya, Khem; Zazubovich, Valter; Picorel Castaño, Rafael; Seibert, Michael; Jankowiak, Ryszard J.

    2011-01-01

    The PSI-CP43' supercomplex of the cyanobacterium Synechocystis PCC 6803, grown under iron-starvation conditions, consists of a trimeric core Photosystem I (PSI) complex and an outer ring of 18 CP43' light-harvesting complexes. We have investigated the electronic structure and excitation energy transfer (EET) pathways within the CP43' (also known as the isiA gene product) ring using low-temperature absorption, fluorescence, fluorescence excitation, and hole-burning (HB) spectroscopies. Analysi...

  15. Vapour-density determinations of Group 5 pentafluorides

    International Nuclear Information System (INIS)

    Vapour-density determinations on the saturated vapours of NbF5, TaF5, and SbF5 at temperatures above their boiling points have been made by a modified Dumas method. The average molecular weights of the vapour-phase species near the boiling points are close to those for the respective trimers. Approaching 4000C (or 3000C for SbF5), however, the major constituent of the vapour is the monomeric pentafluoride. (author)

  16. Altered Enthalpy-Entropy Compensation in Picomolar Transition State Analogues of Human Purine Nucleoside Phosphorylase†

    OpenAIRE

    Edwards, Achelle A.; Mason, Jennifer M.; Clinch, Keith; Tyler, Peter C.; Evans, Gary B.; Schramm, Vern L.

    2009-01-01

    Human purine nucleoside phosphorylase (PNP) belongs to the trimeric class of PNPs and is essential for catabolism of deoxyguanosine. Genetic deficiency of PNP in humans causes a specific T-cell immune deficiency and transition state analogue inhibitors of PNP are in development for treatment of T-cell cancers and autoimmune disorders. Four generations of Immucillins have been developed, each of which contains inhibitors binding with picomolar affinity to human PNP. Full inhibition of PNP occu...

  17. The structure of allophycocyanin B from Synechocystis PCC 6803 reveals the structural basis for the extreme redshift of the terminal emitter in phycobilisomes.

    Science.gov (United States)

    Peng, Pan Pan; Dong, Liang Liang; Sun, Ya Fang; Zeng, Xiao Li; Ding, Wen Long; Scheer, Hugo; Yang, Xiaojing; Zhao, Kai Hong

    2014-10-01

    Allophycocyanin B (AP-B) is one of the two terminal emitters in phycobilisomes, the unique light-harvesting complexes of cyanobacteria and red algae. Its low excitation-energy level and the correspondingly redshifted absorption and fluorescence emission play an important role in funnelling excitation energy from the hundreds of chromophores of the extramembraneous phycobilisome to the reaction centres within the photosynthetic membrane. In the absence of crystal structures of these low-abundance terminal emitters, the molecular basis for the extreme redshift and directional energy transfer is largely unknown. Here, the crystal structure of trimeric AP-B [(ApcD/ApcB)3] from Synechocystis sp. PCC 6803 at 1.75 Å resolution is reported. In the crystal lattice, eight trimers of AP-B form a porous, spherical, 48-subunit assembly of 193 Å in diameter with an internal cavity of 1.1 × 10(6) Å(3). While the overall structure of trimeric AP-B is similar to those reported for many other phycobiliprotein trimers, the chromophore pocket of the α-subunit, ApcD, has more bulky residues that tightly pack the phycocyanobilin (PCB). Ring D of the chromophores is further stabilized by close interactions with ApcB from the adjacent monomer. The combined contributions from both subunits render the conjugated rings B, C and D of the PCB in ApcD almost perfectly coplanar. Together with mutagenesis data, it is proposed that the enhanced planarity effectively extends the conjugation system of PCB and leads to the redshifted absorption (λmax = 669 nm) and fluorescence emission (679 nm) of the ApcD chromophore in AP-B, thereby enabling highly efficient energy transfer from the phycobilisome core to the reaction centres. PMID:25286841

  18. Reversible peptide oligomerization over nanoscale gold surfaces

    OpenAIRE

    Kazushige Yokoyama; Christa D. Catalfamo; Minxuan Yuan

    2015-01-01

    A selective oligomeric formation of amyloid beta 1-40 (Ab1-40) monomers over a nanogold colloidal surface was investigated. An unfolded Ab1-40 monomer is considered to construct a dimer or trimer based oligomeric form with its hydrophobic segment placing outward under an acidic condition. Under a basic condition, a conformation of Ab is expected to take a folded monomeric form with its hydrophilic segment folded inward, avoiding the networking with residual colloidal particles. The most proba...

  19. Collagen-like proteins in pathogenic E. coli strains.

    Directory of Open Access Journals (Sweden)

    Neelanjana Ghosh

    Full Text Available The genome sequences of enterohaemorrhagic E. coli O157:H7 strains show multiple open-reading frames with collagen-like sequences that are absent from the common laboratory strain K-12. These putative collagens are included in prophages embedded in O157:H7 genomes. These prophages carry numerous genes related to strain virulence and have been shown to be inducible and capable of disseminating virulence factors by horizontal gene transfer. We have cloned two collagen-like proteins from E. coli O157:H7 into a laboratory strain and analysed the structure and conformation of the recombinant proteins and several of their constituting domains by a variety of spectroscopic, biophysical, and electron microscopy techniques. We show that these molecules exhibit many of the characteristics of vertebrate collagens, including trimer formation and the presence of a collagen triple helical domain. They also contain a C-terminal trimerization domain, and a trimeric α-helical coiled-coil domain with an unusual amino acid sequence almost completely lacking leucine, valine or isoleucine residues. Intriguingly, these molecules show high thermal stability, with the collagen domain being more stable than those of vertebrate fibrillar collagens, which are much longer and post-translationally modified. Under the electron microscope, collagen-like proteins from E. coli O157:H7 show a dumbbell shape, with two globular domains joined by a hinged stalk. This morphology is consistent with their likely role as trimeric phage side-tail proteins that participate in the attachment of phage particles to E. coli target cells, either directly or through assembly with other phage tail proteins. Thus, collagen-like proteins in enterohaemorrhagic E. coli genomes may have a direct role in the dissemination of virulence-related genes through infection of harmless strains by induced bacteriophages.

  20. Quantitative analysis of phenolic compounds in Chinese hawthorn (Crataegus spp.) fruits by high performance liquid chromatography-electrospray ionisation mass spectrometry.

    Science.gov (United States)

    Liu, Pengzhan; Kallio, Heikki; Lü, Deguo; Zhou, Chuansheng; Yang, Baoru

    2011-08-01

    Eleven major phenolic compounds (hyperoside, isoquercitrin, chlorogenic acid, ideain, epicatechin, two procyanidin (PA) dimers, three PA trimers and a PA dimer-hexoside) were quantified in the fruits of 22 cultivars/origins of three species of the Chinese hawthorn (Crataegus spp.) by HPLC-ESI-MS-SIR. Hyperoside (0.1-0.8mg/g dry mass [DM]), isoquercitrin (0.1-0.3mg/g DM), chlorogenic acid (0.2-1.6mg/g DM), epicatechin (0.9-11.7mg/g DM), PA B2 (0.7-12.4mg/g DM), PA dimer II (0.1-1.5mg/g DM), PA trimer I (0.1-2.7mg/g DM), PA trimer II (0.7-6.9mg/g DM), PA trimer III (0.01-1.2mg/g DM) and a PA dimer-hexoside (trace-1.1mg/g DM) were detected in all the samples. Ideain (0.0-0.7mg/g DM) was found in all the samples except Crataegus scabrifolia. Significant correlations between the contents of individual PA aglycons were observed (r>0.9, P<0.01). A strong correlation between flavonols was also shown (r=0.71, P<0.01). Fruits of Crataegus pinnatifida var. major had higher contents of PAs but lower contents of flavonols compared with Crataegus brettschneideri. The fruits of C. scabrifolia contained the highest level of PA dimer-hexoside, which was present in trace amounts in the fruits of C. pinnatifida. PMID:25214140