Sample records for chimeric cyanovirin-n homolog

  1. Carbohydrate recognition by the antiviral lectin cyanovirin-N

    Fujimoto, Yukiji K.; Green, David F.


    Cyanovirin-N is a cyanobacterial lectin with potent antiviral activity, and has been the focus of extensive pre-clinical investigation as a potential prophylactic for the prevention of the sexual transmission of the human immunodeficiency virus (HIV). Here we present a detailed analysis of carbohydrate recognition by this important protein, using a combination of computational methods, including extensive molecular dynamics simulations and Molecular-Mechanics/ Poisson–Boltzmann/Surface-Area (...

  2. Computational models explain the oligosaccharide specificity of cyanovirin-N

    Fujimoto, Yukiji K.; TerBush, Ryan N.; Patsalo, Vadim; Green, David F.


    The prokaryotic lectin cyanovirin-N (CV-N) is a potent inhibitor of HIV envelope-mediated cell entry, and thus is a leading candidate among a new class of potential anti-HIV microbicides. The activity of CV-N is a result of interactions with the D1 arm of high-mannose oligosaccharides on the viral glycoprotein gp120. Here, we present computationally refined models of CV-N recognition of the di- and trisaccharides that represent the terminal three sugars of the D1 arm by each CV-N binding site...

  3. Incorporation of the HIV-1 microbicide cyanovirin-N in a food product

    Li, Ming; Patton, Dorothy L.; Cosgrove-Sweeney, Yvonne; Ratner, Deena; Rohan, Lisa C.; Cole, Alexander M.; Tarwater, Patrick M.; Gupta, Phalguni; Ramratnam, Bharat


    An urgent need exists for HIV-1 microbicides. Here, we describe the in vivo testing of lactic acid bacteria bioengineered to secrete cyanovirin-N. We fed pigtail macaques a yogurt formulation that used bioengineered strains as a starter culture. Cyanovirin-N expression could be detected in the rectal vault during and immediately after feeding. Ex vivo viral challenge of rectal tissue biopsies revealed that peak viral burden was significantly lower in tissue obtained from experimental animals ...

  4. Carbohydrate recognition by the antiviral lectin cyanovirin-N.

    Fujimoto, Yukiji K; Green, David F


    Cyanovirin-N (CVN) is a cyanobacterial lectin with potent antiviral activity and has been the focus of extensive preclinical investigation as a potential prophylactic for the prevention of the sexual transmission of the human immunodeficiency virus (HIV). Here we present a detailed analysis of carbohydrate recognition by this important protein, using a combination of computational methods, including extensive molecular dynamics simulations and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) energetic analysis. The simulation results strongly suggest that the observed tendency of wild-type CVN to form domain-swapped dimers is the result of a previously unidentified cis-peptide bond present in the monomeric state. The energetic analysis additionally indicates that the highest-affinity ligand for CVN characterized to date (α-Man-(1,2)-α-Man-(1,2)-α-Man) is recognized asymmetrically by the two binding sites. Finally, we are able to provide a detailed map of the role of all binding site functional groups (both backbone and side chain) to various aspects of molecular recognition: general affinity for cognate ligands, specificity for distinct oligosaccharide targets, and the asymmetric recognition of α-Man-(1,2)-α-Man-(1,2)-α-Man. Taken as a whole, these results complement past experimental characterization (both structural and thermodynamic) to provide the most complete understanding of carbohydrate recognition by CVN to date. The results also provide strong support for the application of similar approaches to the understanding of other protein-carbohydrate complexes. PMID:23057413

  5. Rhizosecretion improves the production of Cyanovirin-N in Nicotiana tabacum through simplified downstream processing.

    Madeira, Luisa M; Szeto, Tim H; Ma, Julian K-C; Drake, Pascal M W


    Rhizosecretion has many advantages for the production of recombinant pharmaceuticals, notably facile downstream processing from hydroponic medium. The aim of this study was to increase yields of the HIV microbicide candidate, Cyanovirin-N (CV-N), obtained using this production platform and to develop a simplified methodology for its downstream processing from hydroponic medium. Placing hydroponic cultures on an orbital shaker more than doubled the concentration of CV-N in the hydroponic medium compared to plants which remained stationary, reaching a maximum of approximately 20μg/ml in one week, which is more than 3 times higher than previously reported yields. The protein composition of the hydroponic medium, the rhizosecretome, was characterised in plants cultured with or without the plant growth regulator alpha-napthaleneacetic acid by LC-ESI-MS/MS, and CV-N was the most abundant protein. The issue of large volumes in the rhizosecretion system was addressed by using ion exchange chromatography to concentrate CV-N and partially remove impurities. The semi-purified CV-N was demonstrated to bind to HIV gp120 in an ELISA and to neutralise HIVBa-L with an IC50 of 6nM in a cell-based assay. Rhizosecretion is therefore a practicable and inexpensive method for the production of functional CV-N. PMID:26901579

  6. The highly specific carbohydrate-binding protein cyanovirin-N: structure, anti-HIV/Ebola activity and possibilities for therapy.

    Barrientos, Laura G; Gronenborn, Angela M


    Cyanovirin-N (CV-N), a cyanobacterial lectin, is a potent viral entry inhibitor currently under development as a microbicide against a broad spectrum of enveloped viruses. CV-N was originally identified as a highly active anti-HIV agent and later, as a virucidal agent against other unrelated enveloped viruses such as Ebola, and possibly other viruses. CV-N's antiviral activity appears to involve unique recognition of N-linked high-mannose oligosaccharides, Man-8 and Man-9, on the viral surface glycoproteins. Due to its distinct mode of action and opportunities for harnessing the associated interaction for therapeutic intervention, a substantial body of research on CV-N has accumulated since its discovery in 1997. In this review we focus in particular on structural studies on CV-N and their relationship to biological activity. PMID:15638789

  7. Polyclonal immunoglobulins from a chronic hepatitis C virus patient protect human liver-chimeric mice from infection with a homologous hepatitis C virus strain

    Vanwolleghem, Thomas; Bukh, Jens; Meuleman, Philip;


    chimeric mice, the inoculum was pre-incubated in vitro at an IgG concentration normally observed in humans. Conclusion: Polyclonal IgG from a patient with a long-standing HCV infection not only displays neutralizing activity in vitro using the HCVpp system, but also conveys sterilizing immunity toward the......The role of the humoral immune response in the natural course of hepatitis C virus (HCV) infection is widely debated. Most chronically infected patients have immunoglobulin G (IgG) antibodies capable of neutralizing HCV pseudoparticles (HCVpp) in vitro. It is, however, not clear whether these Ig......G can prevent a de novo HCV infection in vivo and contribute to the control of viremia in infected individuals. We addressed this question with homologous in vivo protection studies in human liver-urokinase-type plasminogen activator (uPA)(+/+) severe combined immune deficient (SCID) mice. Chimeric mice...

  8. Functional analysis of chimeric genes obtained by exchanging homologous domains of the mouse mdr1 and mdr2 genes.

    Buschman, E; Gros, P.


    A full-length cDNA clone for the mouse mdr1 gene can confer multidrug resistance when introduced by transfection into otherwise drug-sensitive cells. In the same assay, a full-length cDNA clone for a closely related member of the mouse mdr gene family, mdr2, fails to confer multidrug resistance. To identify the domains of mdr1 which are essential for multidrug resistance and which may be functionally distinct in mdr2, we have constructed chimeric cDNA molecules in which discrete domains of md...

  9. Interaction of plant chimeric calcium/calmodulin-dependent protein kinase with a homolog of eukaryotic elongation factor-1alpha

    Wang, W.; Poovaiah, B. W.


    A chimeric Ca2+/calmodulin-dependent protein kinase (CCaMK) was previously cloned and characterized in this laboratory. To investigate the biological functions of CCaMK, the yeast two-hybrid system was used to isolate genes encoding proteins that interact with CCaMK. One of the cDNA clones obtained from the screening (LlEF-1alpha1) has high similarity with the eukaryotic elongation factor-1alpha (EF-1alpha). CCaMK phosphorylated LlEF-1alpha1 in a Ca2+/calmodulin-dependent manner. The phosphorylation site for CCaMK (Thr-257) was identified by site-directed mutagenesis. Interestingly, Thr-257 is located in the putative tRNA-binding region of LlEF-1alpha1. An isoform of Ca2+-dependent protein kinase (CDPK) phosphorylated multiple sites of LlEF-1alpha1 in a Ca2+-dependent but calmodulin-independent manner. Unlike CDPK, CCaMK phosphorylated only one site, and this site is different from CDPK phosphorylation sites. This suggests that the phosphorylation of EF-1alpha by these two kinases may have different functional significance. Although the phosphorylation of LlEF-1alpha1 by CCaMK is Ca2+/calmodulin-dependent, in vitro binding assays revealed that CCaMK binds to LlEF-1alpha1 in a Ca2+-independent manner. This was further substantiated by coimmunoprecipitation of CCaMK and EF-1alpha using the protein extract from lily anthers. Dissociation of CCaMK from EF-1alpha by Ca2+ and phosphorylation of EF-1alpha by CCaMK in a Ca2+/calmodulin-dependent manner suggests that these interactions may play a role in regulating the biological functions of EF-1alpha.

  10. Crystal molecular dynamics simulations to speed up MM/PB(GB)SA evaluation of binding free energies of di-mannose deoxy analogs with P51G-m4-Cyanovirin-N.

    Vorontsov, Ivan I; Miyashita, Osamu


    Complexes of two Cyanovirin-N (CVN) mutants, m4-CVN and P51G-m4-CVN, with deoxy di-mannose analogs were employed as models to generate conformational ensembles using explicit water Molecular Dynamics (MD) simulations in solution and in crystal environment. The results were utilized for evaluation of binding free energies with the molecular mechanics Poisson-Boltzmann (or Generalized Born) surface area, MM/PB(GB)SA, methods. The calculations provided the ranking of deoxy di-mannose ligands affinity in agreement with available qualitative experimental evidences. This confirms the importance of the hydrogen-bond network between di-mannose 3'- and 4'-hydroxyl groups and the protein binding site B(M) as a basis of the CVN activity as an effective HIV fusion inhibitor. Comparison of binding free energies averaged over snapshots from the solution and crystal simulations showed high promises in the use of the crystal matrix for acceleration of the conformational ensemble generation, the most time consuming step in MM/PB(GB)SA approach. Correlation between energy values based on solution versus crystal ensembles is 0.95 for both MM/PBSA and MM/GBSA methods. PMID:20949512

  11. Two RNAs or DNAs May Artificially Fuse Together at a Short Homologous Sequence (SHS) during Reverse Transcription or Polymerase Chain Reactions, and Thus Reporting an SHS-Containing Chimeric RNA Requires Extra Caution.

    Xie, Bingkun; Yang, Wei; Ouyang, Yongchang; Chen, Lichan; Jiang, Hesheng; Liao, Yuying; Liao, D Joshua


    Tens of thousands of chimeric RNAs have been reported. Most of them contain a short homologous sequence (SHS) at the joining site of the two partner genes but are not associated with a fusion gene. We hypothesize that many of these chimeras may be technical artifacts derived from SHS-caused mis-priming in reverse transcription (RT) or polymerase chain reactions (PCR). We cloned six chimeric complementary DNAs (cDNAs) formed by human mitochondrial (mt) 16S rRNA sequences at an SHS, which were similar to several expression sequence tags (ESTs).These chimeras, which could not be detected with cDNA protection assay, were likely formed because some regions of the 16S rRNA are reversely complementary to another region to form an SHS, which allows the downstream sequence to loop back and anneal at the SHS to prime the synthesis of its complementary strand, yielding a palindromic sequence that can form a hairpin-like structure.We identified a 16S rRNA that ended at the 4th nucleotide(nt) of the mt-tRNA-leu was dominant and thus should be the wild type. We also cloned a mouse Bcl2-Nek9 chimeric cDNA that contained a 5-nt unmatchable sequence between the two partners, contained two copies of the reverse primer in the same direction but did not contain the forward primer, making it unclear how this Bcl2-Nek9 was formed and amplified. Moreover, a cDNA was amplified because one primer has 4 nts matched to the template, suggesting that there may be many more artificial cDNAs than we have realized, because the nuclear and mt genomes have many more 4-nt than 5-nt or longer homologues. Altogether, the chimeric cDNAs we cloned are good examples suggesting that many cDNAs may be artifacts due to SHS-caused mis-priming and thus greater caution should be taken when new sequence is obtained from a technique involving DNA polymerization. PMID:27148738

  12. Two RNAs or DNAs May Artificially Fuse Together at a Short Homologous Sequence (SHS) during Reverse Transcription or Polymerase Chain Reactions, and Thus Reporting an SHS-Containing Chimeric RNA Requires Extra Caution

    Xie, Bingkun; Yang, Wei; Ouyang, Yongchang; Chen, Lichan; Jiang, Hesheng; Liao, Yuying; Liao, D. Joshua


    Tens of thousands of chimeric RNAs have been reported. Most of them contain a short homologous sequence (SHS) at the joining site of the two partner genes but are not associated with a fusion gene. We hypothesize that many of these chimeras may be technical artifacts derived from SHS-caused mis-priming in reverse transcription (RT) or polymerase chain reactions (PCR). We cloned six chimeric complementary DNAs (cDNAs) formed by human mitochondrial (mt) 16S rRNA sequences at an SHS, which were similar to several expression sequence tags (ESTs).These chimeras, which could not be detected with cDNA protection assay, were likely formed because some regions of the 16S rRNA are reversely complementary to another region to form an SHS, which allows the downstream sequence to loop back and anneal at the SHS to prime the synthesis of its complementary strand, yielding a palindromic sequence that can form a hairpin-like structure.We identified a 16S rRNA that ended at the 4th nucleotide(nt) of the mt-tRNA-leu was dominant and thus should be the wild type. We also cloned a mouse Bcl2-Nek9 chimeric cDNA that contained a 5-nt unmatchable sequence between the two partners, contained two copies of the reverse primer in the same direction but did not contain the forward primer, making it unclear how this Bcl2-Nek9 was formed and amplified. Moreover, a cDNA was amplified because one primer has 4 nts matched to the template, suggesting that there may be many more artificial cDNAs than we have realized, because the nuclear and mt genomes have many more 4-nt than 5-nt or longer homologues. Altogether, the chimeric cDNAs we cloned are good examples suggesting that many cDNAs may be artifacts due to SHS-caused mis-priming and thus greater caution should be taken when new sequence is obtained from a technique involving DNA polymerization. PMID:27148738

  13. Electroejaculation of chimeric rats

    McCoy, Marina R.; Montonye, Daniel; Bryda, Elizabeth C.


    With the advent of genetic engineering of rodents came the need to assess fertility and germline competency, especially in chimeric rodents generated using embryonic stem cells. Traditional methods rely on natural mating and progeny testing, which is time- and cost-intensive. Electroejaculation is a faster method of collecting sperm for genetic analysis and offers the additional benefit of using fewer animals. This column describes a refined electroejaculation technique for chimeric rats usin...

  14. Electroejaculation of chimeric rats.

    McCoy, Marina R; Montonye, Daniel; Bryda, Elizabeth C


    With the advent of genetic engineering of rodents came the need to assess fertility and germline competency, especially in chimeric rodents generated using embryonic stem cells. Traditional methods rely on natural mating and progeny testing, which is time- and cost-intensive. Electroejaculation is a faster method of collecting sperm for genetic analysis and offers the additional benefit of using fewer animals. This column describes a refined electroejaculation technique for chimeric rats using light gas anesthesia and a custom-made platform for sperm collection. PMID:23689457

  15. Chimeric Pestivirus Experimental Vaccines.

    Reimann, Ilona; Blome, Sandra; Beer, Martin


    Chimeric pestiviruses have shown great potential as marker vaccine candidates against pestiviral infections. Exemplarily, we describe here the construction and testing of the most promising classical swine fever vaccine candidate "CP7_E2alf" in detail. The description is focused on classical cloning technologies in combination with reverse genetics. PMID:26458840

  16. Directed homology

    Fahrenberg, Uli


    We introduce a new notion of directed homology for semicubical sets. We show that it respects directed homotopy and is functorial, and that it appears to enjoy some good algebraic properties. Our work has applications to higher-dimensional automata.......We introduce a new notion of directed homology for semicubical sets. We show that it respects directed homotopy and is functorial, and that it appears to enjoy some good algebraic properties. Our work has applications to higher-dimensional automata....

  17. Exploration of genetically encoded voltage indicators based on a chimeric voltage sensing domain

    Yukiko Mishina


    We recently introduced a new VSFP design in which the voltage-sensing domain (VSD is sandwiched between a FRET pair of fluorescent proteins (termed VSFP-Butterflies and also demonstrated a series of chimeric VSD in which portions of the VSD of Ciona intestinalis voltage-sensitive phosphatase (Ci-VSP are substituted by homologous portions of a voltage-gated potassium channel subunit. These chimeric VSD had faster sensing kinetics than that of the native Ci-VSD. Here, we describe a new set of VSFPs that combine chimeric VSD with the Butterfly structure. We show that these chimeric VSFP-Butterflies can report membrane voltage oscillations of up to 200 Hz in cultured cells and report sensory evoked cortical population responses in living mice. This class of GEVIs may be suitable for imaging of brain rhythms in behaving mammalians.

  18. Chimeric enzymes with improved cellulase activities

    Xu, Qi; Baker, John O; Himmel, Michael E


    Nucleic acid molecules encoding chimeric cellulase polypeptides that exhibit improved cellulase activities are disclosed herein. The chimeric cellulase polypeptides encoded by these nucleic acids and methods to produce the cellulases are also described, along with methods of using chimeric cellulases for the conversion of cellulose to sugars such as glucose.

  19. Targeting duplex DNA with chimeric α,β-triplex-forming oligonucleotides.

    Kolganova, N A; Shchyolkina, A K; Chudinov, A V; Zasedatelev, A S; Florentiev, V L; Timofeev, E N


    Triplex-directed DNA recognition is strictly limited by polypurine sequences. In an attempt to address this problem with synthetic biology tools, we designed a panel of short chimeric α,β-triplex-forming oligonucleotides (TFOs) and studied their interaction with fluorescently labelled duplex hairpins using various techniques. The hybridization of hairpin with an array of chimeric probes suggests that recognition of double-stranded DNA follows complicated rules combining reversed Hoogsteen and non-canonical homologous hydrogen bonding. In the presence of magnesium ions, chimeric TFOs are able to form highly stable α,β-triplexes, as indicated by native gel-electrophoresis, on-array thermal denaturation and fluorescence-quenching experiments. CD spectra of chimeric triplexes exhibited features typically observed for anti-parallel purine triplexes with a GA or GT third strand. The high potential of chimeric α,β-TFOs in targeting double-stranded DNA was demonstrated in the EcoRI endonuclease protection assay. In this paper, we report, for the first time, the recognition of base pair inversions in a duplex by chimeric TFOs containing α-thymidine and α-deoxyguanosine. PMID:22641847

  20. Chimeric Foot-and-Mouth Disease Viruses: Evaluation of Their Efficacy as Potential Marker Vaccines in Cattle

    Previous work in swine has demonstrated that full protection against Foot-and-Mouth Disease (FMD) can be achieved following vaccination with chimeric Foot-and-Mouth Disease Virus (FMDV) vaccines, whereby the VP1 G-H loop has been substituted with a non-homologous alternative. If proven to be effect...

  1. Homology, Analogy, and Ethology.

    Beer, Colin G.


    Because the main criterion of structural homology (the principle of connections) does not exist for behavioral homology, the utility of the ethological concept of homology has been questioned. The confidence with which behavioral homologies can be claimed varies inversely with taxonomic distance. Thus, conjectures about long-range phylogenetic…

  2. Progress in Chimeric Vector and Chimeric Gene Based Cardiovascular Gene Therapy

    HU Chun-Song; YOON Young-sup; ISNER Jeffrey M.; LOSORDO Douglas W.


    Gene therapy for cardiovascular diseases has developed from preliminary animal experiments to clinical trials. However, vectors and target genes used currently in gene therapy are mainly focused on viral, nonviral vector and single target gene or monogene. Each vector system has a series of advantages and limitations. Chimeric vectors which combine the advantages of viral and nonviral vector,chimeric target genes which combine two or more target genes and novel gene delivery modes are being developed. In this article, we summarized the progress in chimeric vectors and chimeric genes based cardiovascular gene therapy, which including proliferative or occlusive vascular diseases such as atheroslerosis and restenosis, hypertonic vascular disease such as hypertension and cardiac diseases such as myocardium ischemia, dilated cardiomyopathy and heart failure, even heart transplantation. The development of chimeric vector, chimeric gene and their cardiovascular gene therapy is promising.

  3. Intersection homology Betti numbers

    Durfee, A H


    A generalization of the formula of Fine and Rao for the ranks of the intersection homology groups of a complex algebraic variety is given. The proof uses geometric properties of intersection homology and mixed Hodge theory.

  4. Lectures on functor homology

    Touzé, Antoine


    This book features a series of lectures that explores three different fields in which functor homology (short for homological algebra in functor categories) has recently played a significant role. For each of these applications, the functor viewpoint provides both essential insights and new methods for tackling difficult mathematical problems. In the lectures by Aurélien Djament, polynomial functors appear as coefficients in the homology of infinite families of classical groups, e.g. general linear groups or symplectic groups, and their stabilization. Djament’s theorem states that this stable homology can be computed using only the homology with trivial coefficients and the manageable functor homology. The series includes an intriguing development of Scorichenko’s unpublished results. The lectures by Wilberd van der Kallen lead to the solution of the general cohomological finite generation problem, extending Hilbert’s fourteenth problem and its solution to the context of cohomology. The focus here is o...

  5. Lectures on knot homology

    Nawata, Satoshi


    We provide various formulations of knot homology that are predicted by string dualities. In addition, we also explain the rich algebraic structure of knot homology which can be understood in terms of geometric representation theory in these formulations. These notes are based on lectures in the workshop "Physics and Mathematics of Link Homology" at Centre de Recherches Math\\'ematiques, Universit\\'e de Montr\\'eal.

  6. Blood chimerism in a dizygotic dichorionic pregnancy.

    Jang, Ja-Hyun; Jung, Haiyoung; Kim, Jong-Hwa; Park, Won-Soon; Kim, Sun-Hee


    Blood chimerism in twins is known to occur through the transfer of hematopoietic stem cells between the fetuses via a common placenta. We present a case of blood chimerism in a dizygotic dichorionic twin pregnancy. The female twin was delivered at 34 weeks of gestation, and the male twin was stillborn. Pathologic examination confirmed dichorionic diamniotic placentas. The karyotype of the female child was obtained using peripheral blood sample, and it revealed a mixture of 46,XX and 46,XY cells (chi 46,XY[13]/46,XX[7]). FISH analysis performed on the buccal cells by using CEP X/Y probe (Abbott Molecular Inc., USA) revealed 100% XX signals (nuc ish Xcen(DXZ1x2)[500]). Gross examination of the external genitalia and abdominal ultrasonography revealed no definitive abnormal findings in relation to sex differentiation. When XX/XY chimerism is present in blood lymphocytes, careful examination of external genitalia and reproductive organs and further studies are required to detect chimerism in non-hematopoetic tissues. This is a rare case of blood chimerism in dichorionic placentas, in contrast to those in monochorionic placentas. PMID:20890086

  7. Homological stabilizer codes

    In this paper we define homological stabilizer codes on qubits which encompass codes such as Kitaev’s toric code and the topological color codes. These codes are defined solely by the graphs they reside on. This feature allows us to use properties of topological graph theory to determine the graphs which are suitable as homological stabilizer codes. We then show that all toric codes are equivalent to homological stabilizer codes on 4-valent graphs. We show that the topological color codes and toric codes correspond to two distinct classes of graphs. We define the notion of label set equivalencies and show that under a small set of constraints the only homological stabilizer codes without local logical operators are equivalent to Kitaev’s toric code or to the topological color codes. - Highlights: ► We show that Kitaev’s toric codes are equivalent to homological stabilizer codes on 4-valent graphs. ► We show that toric codes and color codes correspond to homological stabilizer codes on distinct graphs. ► We find and classify all 2D homological stabilizer codes. ► We find optimal codes among the homological stabilizer codes.

  8. Chimerism in health, transplantation and autoimmunity

    Koopmans, Marije; Kremer Hovinga, Idske Cornelia Lydia


    The term “chimerism” originates from Greek mythology and refers to the creature Chimaera, whose body was in front a lion, the back a serpent and the midsection a goat. In medicine, the term chimerism refers to an individual, organ or part consisting of tissues of diverse genetic constitution. Pregna

  9. Sutures and contact homology I

    Colin, Vincent; Ghiggini, Paolo; Honda, Ko; Hutchings, Michael


    We define a relative version of contact homology for contact manifolds with convex boundary, and prove basic properties of this relative contact homology. Similar considerations also hold for embedded contact homology.

  10. Braid Floer homology

    van den Berg, J. B.; Ghrist, R.; Vandervorst, R. C.; Wójcik, W.


    Area-preserving diffeomorphisms of a 2-disc can be regarded as time-1 maps of (non-autonomous) Hamiltonian flows on R / Z ×D2. The periodic flow-lines define braid (conjugacy) classes, up to full twists. We examine the dynamics relative to such braid classes and define a new invariant for such classes, the BRAID FLOER HOMOLOGY. This refinement of Floer homology, originally used for the Arnol'd Conjecture, yields a Morse-type forcing theory for periodic points of area-preserving diffeomorphisms of the 2-disc based on braiding. Contributions of this paper include (1) a monotonicity lemma for the behavior of the nonlinear Cauchy-Riemann equations with respect to algebraic lengths of braids; (2) establishment of the topological invariance of the resulting braid Floer homology; (3) a shift theorem describing the effect of twisting braids in terms of shifting the braid Floer homology; (4) computation of examples; and (5) a forcing theorem for the dynamics of Hamiltonian disc maps based on braid Floer homology.

  11. Development of GR/MR Chimeric Receptors and Their Response to Steroid Hormones


    We have established an effective and reliable technique of developing GR/MR chimeric receptors by DNA homologous recombination. To develop the method we transformed several different E. coli strains with a linearized plasmid containing full length of mGR(mouse GR) and hormone binding domain(HBD) of rMR(rat MR), the linear DNA undergoes recombination due to the homology of the mGR and the rMR and recircularize , and propagation in E. coli. PCR was performed to screen correct construction in which fusion between GR and MR took place. The constructs were digested with appropriate restriction endonucleases to test probable fusion sites of GR and HBD of MR. Precise fusion sites of GR and MR for constructs AB1157 # 2 , AB1157 # 18, AB 1157 # 22, AB1157 # 32, CMK603 # 6 were verified by DNA sequencing. Trans fection of COS- 7 cells with the constructs and subsequent treatment of transfected COS-7 cells with steroid hormones were carried out, the results showed that the constructs gave response to tested hormones. The study suggested that the GR/MR chimeric receptors can give rise to fusion proteins and their interactive function between hormone and receptor.

  12. Gorenstein homological dimensions

    Holm, Henrik Granau


    In basic homological algebra, the projective, injective and 2at dimensions of modules play an important and fundamental role. In this paper, the closely related Gorenstein projective, Gorenstein injective and Gorenstein 2at dimensions are studied. There is a variety of nice results about Gorenstein...... dimensions over special commutative noetherian rings; very often local Cohen–Macaulay rings with a dualizing module. These results are done by Avramov, Christensen, Enochs, Foxby, Jenda, Martsinkovsky and Xu among others. The aim of this paper is to generalize these results, and to give homological...

  13. Introduction to sutured Floer homology

    Altman, Irida


    This article is a standalone introduction to sutured Floer homology for graduate students in geometry and topology. It is divided into three parts. The first part is an introductory level exposition of Lagrangian Floer homology. The second part is a construction of Heegaard Floer homology as a special, and slightly modified, case of Lagrangian Floer homology. The third part covers the background on sutured manifolds, the definition of sutured Floer homology, as well as a discussion of its mos...


    Menshikova, Galina


    The aim of this study was to investigate holistic / feature processing for encoding face expressions employing the chimeric face technique. In the course of our experiment we tested the recognition accuracy of universal and chimeric countenance. As the study has revealed there was a considerable difference between distributions of subject responses depending on the localization of expression features (top / bottom parts of the face). For chimeric face identification accuracy substantially dec...

  15. Pseudocycles and Integral Homology

    Zinger, Aleksey


    We describe a natural isomorphism between the set of equivalence classes of pseudocycles and the integral homology groups of a smooth manifold. Our arguments generalize to settings well-suited for applications in enumerative algebraic geometry and for construction of the virtual fundamental class in the Gromov-Witten theory.

  16. Homology cylinders and sutured manifolds for homologically fibered knots

    Goda, Hiroshi; Sakasai, Takuya


    Sutured manifolds defined by Gabai are useful in the geometrical study of knots and 3-dimensional manifolds. On the other hand, homology cylinders are in an important position in the recent theory of homology cobordisms of surfaces and finite-type invariants. We study a relationship between them by focusing on sutured manifolds associated with a special class of knots which we call {\\it homologically fibered knots}. Then we use invariants of homology cylinders to give applications to...

  17. An E2-Substituted Chimeric Pestivirus With DIVA Vaccine Properties

    Rasmussen, Thomas Bruun; Uttenthal, Åse; Nielsen, Jens;

    An advantage of the use of chimeric pestiviruses as modified live vaccines against classical swine fever (CSF) resides in their capacity to be manipulated to achieve the characteristics desired for safe and efficacious DIVA vaccines. We have recently generated a new chimeric virus, Riems26_E2gif...

  18. Persistent Homology of Filtered Covers

    Fraser, Maia


    We prove an extension to the simplicial Nerve Lemma which establishes isomorphism of persistent homology groups, in the case where the covering spaces are filtered. While persistent homology is now widely used in topological data analysis, the usual Nerve Lemma does not provide isomorphism of persistent homology groups. Our argument involves some homological algebra: the key point being that although the maps produced in the standard proof of the Nerve Lemma do not commute as maps of chain complexes, the maps they induce on homology do.

  19. Equivariant elliptic homology

    In a previous paper we studied the modular properties of indices of elliptic operators on twisted loop spaces of manifolds with finite group actions. This motivates the introduction of the universal twisted elliptic genus. This genus can be interpreted as a ring homomorphism from the equivariant bordism ring MU*G to a ring Ell*G. It is shown that the functor X→Ell*G=MU*G(X)xMU*GEll*G defines an equivariant homology theory, and that the associated cohomology theory satisfies a conjecture of Atiyah and Segal about generalized Lefchetz formulas. (author). 24 refs

  20. Intersection homology Kunneth theorems

    Friedman, Greg


    Cohen, Goresky and Ji showed that there is a Kunneth theorem relating the intersection homology groups $I^{\\bar p}H_*(X\\times Y)$ to $I^{\\bar p}H_*(X)$ and $I^{\\bar p}H_*(Y)$, provided that the perversity $\\bar p$ satisfies rather strict conditions. We consider biperversities and prove that there is a K\\"unneth theorem relating $I^{\\bar p,\\bar q}H_*(X\\times Y)$ to $I^{\\bar p}H_*(X)$ and $I^{\\bar q}H_*(Y)$ for all choices of $\\bar p$ and $\\bar q$. Furthermore, we prove that the Kunneth theorem...

  1. Quantifying homologous replacement of loci between haloarchaeal species.

    Williams, David; Gogarten, J Peter; Papke, R Thane


    In vitro studies of the haloarchaeal genus Haloferax have demonstrated their ability to frequently exchange DNA between species, whereas rates of homologous recombination estimated from natural populations in the genus Halorubrum are high enough to maintain random association of alleles between five loci. To quantify the effects of gene transfer and recombination of commonly held (relaxed core) genes during the evolution of the class Halobacteria (haloarchaea), we reconstructed the history of 21 genomes representing all major groups. Using a novel algorithm and a concatenated ribosomal protein phylogeny as a reference, we created a directed horizontal genetic transfer (HGT) network of contemporary and ancestral genomes. Gene order analysis revealed that 90% of testable HGTs were by direct homologous replacement, rather than nonhomologous integration followed by a loss. Network analysis revealed an inverse log-linear relationship between HGT frequency and ribosomal protein evolutionary distance that is maintained across the deepest divergences in Halobacteria. We use this mathematical relationship to estimate the total transfers and amino acid substitutions delivered by HGTs in each genome, providing a measure of chimerism. For the relaxed core genes of each genome, we conservatively estimate that 11-20% of their evolution occurred in other haloarchaea. Our findings are unexpected, because the transfer and homologous recombination of relaxed core genes between members of the class Halobacteria disrupts the coevolution of genes; however, the generation of new combinations of divergent but functionally related genes may lead to adaptive phenotypes not available through cumulative mutations and recombination within a single population. PMID:23160063

  2. Discovery of mitochondrial chimeric-gene associated with cytoplasmic male sterility of HL-rice


    The mitochondrial genome libraries of HL-type sterile line(A) and maintainer line(B) have been constructed.Mitochondrial gene, atp6, was used to screen libraries, due to the different Southern and Northern blot results between sterile and maintainer line. Sequencing analysis of positive clones proved that there were two copies of atp6 gene in sterile line and only one in maintainer line. One copy of atpt6 in sterile line was same to that in maintainer line; the other showed different flanking sequence from the 49th nucleotide downstream of the termination codon of atp6 gene. A new chimeric gene, orfH79, was found in the region. OrfH79 had homology to mitochondrial gene coxⅡ and orfl07, and was special to HL-sterile cytoplasm.``

  3. Functional participation of a nifH-arsA2 chimeric fusion gene in arsenic reduction by Escherichia coli

    The NifH (dimer) and ArsA proteins are structural homologs and share common motifs like nucleotide-binding domains, signal transduction domains and also possible similar metal center ligands. Given the similarity between two proteins, we investigated if the NifH protein from Azotobacter vinelandii could functionally substitute for the ArsA1 half of the ArsA protein of Escherichia coli. The chimeric NifH-ArsA2 protein was expressed and detected in the E. coli strain by Western blotting. Growth comparisons of E. coli strains containing plasmids encoding for complete ArsA, partial ArsA (ArsA2) or chimeric ArsA (NifH-ArsA2) in media with increasing sodium arsenite concentrations (0-5 mM) showed that the chimeric NifH-ArsA2 could substitute for the ArsA. This functional complementation demonstrated the strong conservation of essential domains that have been maintained in NifH and ArsA even after their divergence to perform varied functions

  4. 2-categories and cyclic homology

    Slevin, Paul


    The topic of this thesis is the application of distributive laws between comonads to the theory of cyclic homology. Explicitly, our main aims are: 1) To study how the cyclic homology of associative algebras and of Hopf algebras in the original sense of Connes and Moscovici arises from a distributive law, and to clarify the role of different notions of bimonad in this generalisation. 2) To extend the procedure of twisting the cyclic homology of a unital associative algebra to any duplicial obj...

  5. Matrix Factorizations and Kauffman Homology

    Gukov, S; Gukov, Sergei; Walcher, Johannes


    The topological string interpretation of homological knot invariants has led to several insights into the structure of the theory in the case of sl(N). We study possible extensions of the matrix factorization approach to knot homology for other Lie groups and representations. In particular, we introduce a new triply graded theory categorifying the Kauffman polynomial, test it, and predict the Kauffman homology for several simple knots.

  6. The Geometry of Homological Triangles

    Smarandache, Florentin


    This book is addressed to students, professors and researchers of geometry, who will find herein many interesting and original results. The originality of the book The Geometry of Homological Triangles consists in using the homology of triangles as a "filter" through which remarkable notions and theorems from the geometry of the triangle are unitarily passed. Our research is structured in seven chapters, the first four are dedicated to the homology of the triangles, while the last ones to their applications.

  7. Homology of L_{\\infty}-Algebras and Cyclic Homology

    Khalkhali, Masoud


    A classical result of Loday-Quillen and Tsygan states that the Lie algebra homology of the algebra of stable matrices over an associative algebra is isomorphic, as a Hopf algebra, to the exterior algebra of the cyclic homology of the algebra. In this paper we develop the necessary tools needed to extend extend this result to the category of L_{\\infty} algebras.

  8. Do chimeric sponges have improved chances of survival?

    Maldonado, Manuel


    It has been suggested that the capacity of fusion with both kin and genetically unrelated conspecifics to form chimeras (i.e. individuals with a mixture of genetically different cells) is evolutionarily retained In several phyla because the resulting organism obtains some selective advantages over non-chimeric conspecifics. Many demosponges are known to have fusible larvae that form young chimeric sponges, but the ecological and evolutionary significance of this phenom...

  9. K-Kolmogorov homology groups

    In the present work we use the idea of the K-groups to define the K-Kolmogorov homology groups, and their induced homomorphisms and boundary operators for the case of a pair of discrete coefficient groups, where K denotes a locally-finite simplicial complex. Moreover, we prove that our homology construction is exact. (author)

  10. Relative Homological Algebra Volume 1


    This is the second revised edition of an introduction to contemporary relative homological algebra. It supplies important material essential to understand topics in algebra, algebraic geometry and algebraic topology. Each section comes with exercises providing practice problems for students as well as additional important results for specialists. The book is also suitable for an introductory course in commutative and ordinary homological algebra.

  11. Mod two homology and cohomology

    Hausmann, Jean-Claude


    Cohomology and homology modulo 2 helps the reader grasp more readily the basics of a major tool in algebraic topology. Compared to a more general approach to (co)homology this refreshing approach has many pedagogical advantages: It leads more quickly to the essentials of the subject, An absence of signs and orientation considerations simplifies the theory, Computations and advanced applications can be presented at an earlier stage, Simple geometrical interpretations of (co)chains. Mod 2 (co)homology was developed in the first quarter of the twentieth century as an alternative to integral homology, before both became particular cases of (co)homology with arbitrary coefficients. The first chapters of this book may serve as a basis for a graduate-level introductory course to (co)homology. Simplicial and singular mod 2 (co)homology are introduced, with their products and Steenrod squares, as well as equivariant cohomology. Classical applications include Brouwer's fixed point theorem, Poincaré duality, Borsuk-Ula...

  12. Chimeric autologous/allogeneic constructs for skin regeneration.

    Rasmussen, Cathy Ann; Tam, Joshua; Steiglitz, Barry M; Bauer, Rebecca L; Peters, Noel R; Wang, Ying; Anderson, R Rox; Allen-Hoffmann, B Lynn


    The ideal treatment for severe cutaneous injuries would eliminate the need for autografts and promote fully functional, aesthetically pleasing autologous skin regeneration. NIKS progenitor cell-based skin tissues have been developed to promote healing by providing barrier function and delivering wound healing factors. Independently, a device has recently been created to "copy" skin by harvesting full-thickness microscopic tissue columns (MTCs) in lieu of autografts traditionally harvested as sheets. We evaluated the feasibility of combining these two technologies by embedding MTCs in NIKS-based skin tissues to generate chimeric autologous/allogeneic constructs. Chimeric constructs have the potential to provide immediate wound coverage, eliminate painful donor site wounds, and promote restoration of a pigmented skin tissue possessing hair follicles, sweat glands, and sebaceous glands. After MTC insertion, chimeric constructs and controls were reintroduced into air-interface culture and maintained in vitro for several weeks. Tissue viability, proliferative capacity, and morphology were evaluated after long-term culture. Our results confirmed successful MTC insertion and integration, and demonstrated the feasibility of generating chimeric autologous/allogeneic constructs that preserved the viability, proliferative capacity, and structure of autologous pigmented skin. These feasibility studies established the proof-of-principle necessary to further develop chimeric autologous/allogeneic constructs for the treatment of complex skin defects. PMID:25102552

  13. Fivebranes and 3-manifold homology

    Gukov, Sergei; Vafa, Cumrun


    Motivated by physical constructions of homological knot invariants, we study their analogs for closed 3-manifolds. We show that fivebrane compactifications provide a universal description of various old and new homological invariants of 3-manifolds. In terms of 3d/3d correspondence, such invariants are given by the Q-cohomology of the Hilbert space of partially topologically twisted 3d N=2 theory T[M_3] on a Riemann surface with defects. We demonstrate this by concrete and explicit calculations in the case of monopole/Heegaard Floer homology and a 3-manifold analog of Khovanov-Rozansky link homology. The latter gives a categorification of Chern-Simons partition function. Some of the new key elements include the explicit form of the S-transform and a novel connection between categorification and a previously mysterious role of Eichler integrals in Chern-Simons theory.

  14. Developmental competence of porcine chimeric embryos produced by aggregation

    Li, Juan; Jakobsen, Jannik E.; Xiong, Qiang;


    either by parthenogenetic activation (PA) or handmade cloning (HMC). Results showed that the developmental competence of chimeric embryos, evaluated based on their blastocyst rate and total cell number per blastocyst, was increased when two whole 2-cell stage embryos (PA or HMC) were aggregated. In...... comparison, when two blastomeres were aggregated, the developmental competence of the chimeric embryos decreased if the blastomeres were either from PA or from HMC embryos, but not if they were from different sources, i.e. one PA and one HMC blastomere. To evaluate the cell contribution in embryo formation......The purpose of our study was to compare the developmental competence and blastomere allocation of porcine chimeric embryos formed by micro-well aggregation. Chimeras were created by aggregating either two blastomeres originating from 2-cell embryos or two whole embryos, where embryos were produced...

  15. Object-oriented persistent homology

    Wang, Bao; Wei, Guo-Wei


    Persistent homology provides a new approach for the topological simplification of big data via measuring the life time of intrinsic topological features in a filtration process and has found its success in scientific and engineering applications. However, such a success is essentially limited to qualitative data classification and analysis. Indeed, persistent homology has rarely been employed for quantitative modeling and prediction. Additionally, the present persistent homology is a passive tool, rather than a proactive technique, for classification and analysis. In this work, we outline a general protocol to construct object-oriented persistent homology methods. By means of differential geometry theory of surfaces, we construct an objective functional, namely, a surface free energy defined on the data of interest. The minimization of the objective functional leads to a Laplace-Beltrami operator which generates a multiscale representation of the initial data and offers an objective oriented filtration process. The resulting differential geometry based object-oriented persistent homology is able to preserve desirable geometric features in the evolutionary filtration and enhances the corresponding topological persistence. The cubical complex based homology algorithm is employed in the present work to be compatible with the Cartesian representation of the Laplace-Beltrami flow. The proposed Laplace-Beltrami flow based persistent homology method is extensively validated. The consistence between Laplace-Beltrami flow based filtration and Euclidean distance based filtration is confirmed on the Vietoris-Rips complex for a large amount of numerical tests. The convergence and reliability of the present Laplace-Beltrami flow based cubical complex filtration approach are analyzed over various spatial and temporal mesh sizes. The Laplace-Beltrami flow based persistent homology approach is utilized to study the intrinsic topology of proteins and fullerene molecules. Based on a

  16. Localization theorems in topological Hochschild homology and topological cyclic homology

    Blumberg, Andrew J


    We construct localization cofiber sequences for the topological Hochschild homology (THH) and topological cyclic homology (TC) of spectral categories. Using a ``global'' construction of the THH and TC of a scheme in terms of the perfect complexes in a spectrally enriched version of the category of unbounded complexes, the sequences specialize to localization cofiber sequences associated to the inclusion of an open subscheme. These are the targets of the cyclotomic trace from the localization sequence of Thomason-Trobaugh in K-theory. We also deduce a version of Thomason's blow-up formula for THH and TC.

  17. Study of cancer-specific chimeric promoters induced by irradiation

    Objective: To combine the radio-inducible CArG element with cancer-specific human telomerase reverse transcriptase (hTERT) gene promoter, and to construct the novel chimeric promoters. Methods: The synthetic hTERT promoters containing different number of radio-inducible CArG elements were constructed, and the activities of the promoters in the cancer cells (HeLa, A549, and MHCC97 cells) and nomal cells (hEL cells) were detected by using luciferase-reporter assays after the treatment of irradiation (a single or fractionated irradiation dose). Results: Synthetic promoter containing 6 repeated CArG units was better in radio-inducibility than any other promoters containing different number of CArG units, and nearly maximum levels obtained at 4-6 Gy. The very low activities of the chimeric promoters could be detected in normal hEL cells. A similar level of reporter gene expression was observed after 3 fractionated doses of 2 Gy compared with a single dose of 6 Gy in cancer cells. Conclusions: The cancer-specific chimeric promoter containing 6 CArG elements showes the best radio-response, and the chimeric promoter system has the potential in cancer gene therapy. (authors)

  18. Virulence, immunogenicity and vaccine properties of a novel chimeric pestivirus

    Rasmussen, Thomas Bruun; Uttenthal, Åse; Reimann, Ilona;


    avirulent and neither chimeric virus nor viral RNA was detected in serum after vaccination. The safety of the vaccine was tested by horizontal transmission to sentinel pigs, which remained uninfected. The vaccine efficacy was examined by challenge infection with classical swine fever virus (CSFV) Eystrup...

  19. Hybrid pseudomonads engineered by two-step homologous recombination acquire novel degradation abilities toward aromatics and polychlorinated biphenyls

    Suenaga, Hikaru [National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan). Bioproduction Research Inst.; Nonaka, Kazuhiko; Goto, Masatoshi [Kyushu Univ., Fukuoka (Japan). Dept. of Bioscience and Biotechnology; Fujihara, Hidehiko; Furukawa, Kensuke [Beppu Univ. (Japan). Dept. of Fermentation and Food Science


    Pseudomonas pseudoalcaligenes KF707 possesses a chromosomally encoded bph gene cluster responsible for the catabolism of biphenyl and polychlorinated biphenyls. Previously, we constructed chimeric versions of the bphA1 gene, which encodes a large subunit of biphenyl dioxygenase, by using DNA shuffling between bphA1 genes from P. pseudoalcaligenes KF707 and Burkholderia xenovorans LB400. In this study, we demonstrate replacement of the bphA1 gene with chimeric bphA1 sequence within the chromosomal bph gene cluster by two-step homologous recombination. Notably, some of the hybrid strains acquired enhanced and/or expanded degradation capabilities for specific aromatic compounds, including single aromatic hydrocarbons and polychlorinated biphenyls. (orig.)


    白银; 王琰; 周丽君; 俞莉章


    To construct and express a human-mouse chimeric antibody against human bladder cancer. Method: The variable region genes of anti-human bladder cancer monoclonal antibody BDI-1 were cloned by RT-PCR. A human-mouse chimeric antibody expression vector was constructed and transfected into CHO cells. The chimeric antibody against bladder cancer was expressed and characterized. Result: Eukaryotic expression vector of the chimeric antibody against human bladder carcinoma was successfully constructed, and was expressed in eukaryotic cells; the expressed chimeric antibody ch-BDI showed same specificity as its parent McAb against human bladder cancer cells. Conclusion: The constructed chimeric antibody was expressed successfully in eukaryotic cells, and the chimeric antibody had desired affinity against human bladder cancer cells.

  1. Grid diagrams and Khovanov homology

    Droz, Jean-Marie; Wagner, Emmanuel


    We explain how to compute the Jones polynomial of a link from one of its grid diagrams and we observe a connection between Bigelow’s homological definition of the Jones polynomial and Kauffman’s definition of the Jones polynomial. Consequently, we prove that the Maslov grading on the Seidel...

  2. Local contact homology and applications

    Hryniewicz, Umberto


    We introduce a local version of contact homology for an isolated periodic orbit $\\gamma$ of the Reeb flow and prove that its rank is uniformly bounded for isolated iterations. Several applications are obtained, including a generalization of Gromoll-Meyer's theorem on the existence of infinitely many simple periodic orbits, resonance relations and conditions for the existence of non-hyperbolic periodic orbits.

  3. Creation of chimeric human/rabbit APOBEC1 with HIV-1 restriction and DNA mutation activities

    Ikeda, Terumasa; Ong, Eugene Boon Beng; Watanabe, Nobumoto; Sakaguchi, Nobuo; Maeda, Kazuhiko; Koito, Atsushi


    APOBEC1 (A1) proteins from lagomorphs and rodents have deaminase-dependent restriction activity against HIV-1, whereas human A1 exerts a negligible effect. To investigate these differences in the restriction of HIV-1 by A1 proteins, a series of chimeric proteins combining rabbit and human A1s was constructed. Homology models of the A1s indicated that their activities derive from functional domains that likely act in tandem through a dimeric interface. The C-terminal region containing the leucine-rich motif and the dimerization domains of rabbit A1 is important for its anti-HIV-1 activity. The A1 chimeras with strong anti-HIV-1 activity were incorporated into virions more efficiently than those without anti-HIV-1 activity, and exhibited potent DNA-mutator activity. Therefore, the C-terminal region of rabbit A1 is involved in both its packaging into the HIV-1 virion and its deamination activity against both viral cDNA and genomic RNA. This study identifies the novel molecular mechanism underlying the target specificity of A1.

  4. High affinity mouse-human chimeric Fab against Hepatitis B surface antigen

    Biplab Bose; Navin Khanna; Subrat K Acharya; Subrata Sinha


    AIM: Passive immunotherapy using antibody against hepatitis B surface antigen (HBsAg) has been advocated in certain cases of Hepatitis B infection. We had earlier reported on the cloning and expression of a high affinity scFv derived from a mouse monoclonal (5S) against HBsAg. However this mouse antibody cannot be used for therapeutic purposes as it may elicit anti-mouse immune responses. Chimerization by replacing mouse constant domains with human ones can reduce the immunogenicity of this antibody.METHODS: We cloned the VH and VL genes of this mouse antibody; and fused them with CH1 domain of human IgG1 and CL domain of human kappa chain respectively. These chimeric genes were cloned into a phagemid vector. After initial screening using the phage display system, the chimeric Fab was expressed in soluble form in E. Coli.RESULTS: The chimeric Fab was purified from the bacterial periplasmic extract. We characterized the chimeric Fab using several in vitro techniques and it was observed that the chimeric molecule retained the high affinity and specificity of the original mouse monoclonal.This chimeric antibody fragment was further expressed in different strains of E> coli to increase the yield.CONCLUSION: We have generated a mouse-human chimeric Fab against HBsAg without any significant loss in binding and epitope specificity. This chimeric Fab fragment can be further modified to generate a fulllength chimeric antibody for therapeutic uses.

  5. Persistent Homology of Collaboration Networks

    C. J. Carstens


    Full Text Available Over the past few decades, network science has introduced several statistical measures to determine the topological structure of large networks. Initially, the focus was on binary networks, where edges are either present or not. Thus, many of the earlier measures can only be applied to binary networks and not to weighted networks. More recently, it has been shown that weighted networks have a rich structure, and several generalized measures have been introduced. We use persistent homology, a recent technique from computational topology, to analyse four weighted collaboration networks. We include the first and second Betti numbers for the first time for this type of analysis. We show that persistent homology corresponds to tangible features of the networks. Furthermore, we use it to distinguish the collaboration networks from similar random networks.

  6. Sequencing and characterisation of rearrangements in three S. pastorianus strains reveals the presence of chimeric genes and gives evidence of breakpoint reuse.

    Sarah K Hewitt

    Full Text Available Gross chromosomal rearrangements have the potential to be evolutionarily advantageous to an adapting organism. The generation of a hybrid species increases opportunity for recombination by bringing together two homologous genomes. We sought to define the location of genomic rearrangements in three strains of Saccharomyces pastorianus, a natural lager-brewing yeast hybrid of Saccharomyces cerevisiae and Saccharomyces eubayanus, using whole genome shotgun sequencing. Each strain of S. pastorianus has lost species-specific portions of its genome and has undergone extensive recombination, producing chimeric chromosomes. We predicted 30 breakpoints that we confirmed at the single nucleotide level by designing species-specific primers that flank each breakpoint, and then sequencing the PCR product. These rearrangements are the result of recombination between areas of homology between the two subgenomes, rather than repetitive elements such as transposons or tRNAs. Interestingly, 28/30 S. cerevisiae-S. eubayanus recombination breakpoints are located within genic regions, generating chimeric genes. Furthermore we show evidence for the reuse of two breakpoints, located in HSP82 and KEM1, in strains of proposed independent origin.

  7. Design of chimeric antigen receptors with integrated controllable transient functions

    Alexandre Juillerat; Alan Marechal; Jean-Marie Filhol; Julien Valton; Aymeric Duclert; Laurent Poirot; Philippe Duchateau


    The ability to control T cells engineered to permanently express chimeric antigen receptors (CARs) is a key feature to improve safety. Here, we describe the development of a new CAR architecture with an integrated switch-on system that permits to control the CAR T-cell function. This system offers the advantage of a transient CAR T-cell for safety while letting open the possibility of multiple cytotoxicity cycles using a small molecule drug.

  8. Design of chimeric antigen receptors with integrated controllable transient functions.

    Juillerat, Alexandre; Marechal, Alan; Filhol, Jean-Marie; Valton, Julien; Duclert, Aymeric; Poirot, Laurent; Duchateau, Philippe


    The ability to control T cells engineered to permanently express chimeric antigen receptors (CARs) is a key feature to improve safety. Here, we describe the development of a new CAR architecture with an integrated switch-on system that permits to control the CAR T-cell function. This system offers the advantage of a transient CAR T-cell for safety while letting open the possibility of multiple cytotoxicity cycles using a small molecule drug. PMID:26750734

  9. Chimeric Proteins to Detect DNA Damage and Mismatches

    McCutchen-Maloney, S; Malfatti, M; Robbins, K M


    The goal of this project was to develop chimeric proteins composed of a DNA mismatch or damage binding protein and a nuclease, as well as methods to detect DNA mismatches and damage. We accomplished this through protein engineering based on using polymerase chain reactions (PCRs) to create chimeras with novel functions for damage and mismatch detection. This project addressed fundamental questions relating to disease susceptibility and radiation-induced damage in cells. It also supported and enhanced LLNL's competency in the emerging field of proteomics. In nature, DNA is constantly being subjected to damaging agents such as exposure to ultraviolet (UV) radiation and various environmental and dietary carcinogens. If DNA damage is not repaired however, mutations in DNA result that can eventually manifest in cancer and other diseases. In addition to damage-induced DNA mutations, single nucleotide polymorphisms (SNPs), which are variations in the genetic sequence between individuals, may predispose some to disease. As a result of the Human Genome Project, the integrity of a person's DNA can now be monitored. Therefore, methods to detect DNA damage, mutations, and SNPs are useful not only in basic research but also in the health and biotechnology industries. Current methods of detection often use radioactive labeling and rely on expensive instrumentation that is not readily available in many research settings. Our methods to detect DNA damage and mismatches employ simple gel electrophoresis and flow cytometry, thereby alleviating the need for radioactive labeling and expensive equipment. In FY2001, we explored SNP detection by developing methods based on the ability of the chimeric proteins to detect mismatches. Using multiplex assays with flow cytometry and fluorescent beads to which the DNA substrates where attached, we showed that several of the chimeras possess greater affinity for damaged and mismatched DNA than for native DNA. This affinity was

  10. The Homological Nature of Entropy

    Pierre Baudot


    Full Text Available We propose that entropy is a universal co-homological class in a theory associated to a family of observable quantities and a family of probability distributions. Three cases are presented: (1 classical probabilities and random variables; (2 quantum probabilities and observable operators; (3 dynamic probabilities and observation trees. This gives rise to a new kind of topology for information processes, that accounts for the main information functions: entropy, mutual-informations at all orders, and Kullback–Leibler divergence and generalizes them in several ways. The article is divided into two parts, that can be read independently. In the first part, the introduction, we provide an overview of the results, some open questions, future results and lines of research, and discuss briefly the application to complex data. In the second part we give the complete definitions and proofs of the theorems A, C and E in the introduction, which show why entropy is the first homological invariant of a structure of information in four contexts: static classical or quantum probability, dynamics of classical or quantum strategies of observation of a finite system.

  11. Chimeras taking shape: potential functions of proteins encoded by chimeric RNA transcripts.

    Frenkel-Morgenstern, Milana; Lacroix, Vincent; Ezkurdia, Iakes; Levin, Yishai; Gabashvili, Alexandra; Prilusky, Jaime; Del Pozo, Angela; Tress, Michael; Johnson, Rory; Guigo, Roderic; Valencia, Alfonso


    Chimeric RNAs comprise exons from two or more different genes and have the potential to encode novel proteins that alter cellular phenotypes. To date, numerous putative chimeric transcripts have been identified among the ESTs isolated from several organisms and using high throughput RNA sequencing. The few corresponding protein products that have been characterized mostly result from chromosomal translocations and are associated with cancer. Here, we systematically establish that some of the putative chimeric transcripts are genuinely expressed in human cells. Using high throughput RNA sequencing, mass spectrometry experimental data, and functional annotation, we studied 7424 putative human chimeric RNAs. We confirmed the expression of 175 chimeric RNAs in 16 human tissues, with an abundance varying from 0.06 to 17 RPKM (Reads Per Kilobase per Million mapped reads). We show that these chimeric RNAs are significantly more tissue-specific than non-chimeric transcripts. Moreover, we present evidence that chimeras tend to incorporate highly expressed genes. Despite the low expression level of most chimeric RNAs, we show that 12 novel chimeras are translated into proteins detectable in multiple shotgun mass spectrometry experiments. Furthermore, we confirm the expression of three novel chimeric proteins using targeted mass spectrometry. Finally, based on our functional annotation of exon organization and preserved domains, we discuss the potential features of chimeric proteins with illustrative examples and suggest that chimeras significantly exploit signal peptides and transmembrane domains, which can alter the cellular localization of cognate proteins. Taken together, these findings establish that some chimeric RNAs are translated into potentially functional proteins in humans. PMID:22588898

  12. Construction, purification, and characterization of a chimeric TH1 antagonist

    Javier-González Luís


    Full Text Available Abstract Background TH1 immune response antagonism is a desirable approach to mitigate some autoimmune and inflammatory reactions during the course of several diseases where IL-2 and IFN-γ are two central players. Therefore, the neutralization of both cytokines could provide beneficial effects in patients suffering from autoimmune or inflammatory illnesses. Results A chimeric antagonist that can antagonize the action of TH1 immunity mediators, IFN-γ and IL-2, was designed, engineered, expressed in E. coli, purified and evaluated for its in vitro biological activities. The TH1 antagonist molecule consists of the extracellular region for the human IFNγ receptor chain 1 fused by a four-aminoacid linker peptide to human 60 N-terminal aminoacid residues of IL-2. The corresponding gene fragments were isolated by RT-PCR and cloned in the pTPV-1 vector. E. coli (W3110 strain was transformed with this vector. The chimeric protein was expressed at high level as inclusion bodies. The protein was partially purified by pelleting and washing. It was then solubilized with strong denaturant and finally refolded by gel filtration. In vitro biological activity of chimera was demonstrated by inhibition of IFN-γ-dependent HLA-DR expression in Colo 205 cells, inhibition of IFN-γ antiproliferative effect on HEp-2 cells, and by a bidirectional effect in assays for IL-2 T-cell dependent proliferation: agonism in the absence versus inhibition in the presence of IL-2. Conclusion TH1 antagonist is a chimeric protein that inhibits the in vitro biological activities of human IFN-γ, and is a partial agonist/antagonist of human IL-2. With these attributes, the chimera has the potential to offer a new opportunity for the treatment of autoimmune and inflammatory diseases.

  13. Chimeric creatures in Greek mythology and reflections in science.

    Bazopoulou-Kyrkanidou, E


    "The Chimaera" in Homer's Iliad, "was of divine stock, not of men, in the forepart a lion, in the hinder a serpent, and in the midst a goat, ellipsis Bellerophon slew her, trusting in the signs of the gods." In Hesiod's Theogony it is emphasized that "Chimaera ellipsis had three heads, one of a grim-eyed lion, another of a goat, and another of a snakeellipsis". In addition to this interspecies animal chimera, human/animal chimeras are referred to in Greek mythology, preeminent among them the Centaurs and the Minotaur. The Centaurs, as horse/men, first appear in Geometric and early Archaic art, but in the literature not until early in the fifth century B.C. The bullheaded-man Minotaur, who is not certainly attested in the literary evidence until circa 500 B.C., first appears in art about 650 B.C. Attempts, in the fourth century B.C. and thereafter, to rationalize their mythical appearance were in vain; their chimeric nature retained its fascinating and archetypal form over the centuries. Early in the 1980s, experimental sheep/goat chimeras were produced removing the reproductive barrier between these two animal species. Late in the 1990s, legal, political, ethical, and moral fights loomed over a patent bid on human/animal chimeras. Chimeric technology is recently developed; however, the concept of chimerism has existed in literary and artistic form in ancient mythology. This is yet another example where art and literature precede scientific research and development. PMID:11337752

  14. Chimeric elk/mouse prion proteins in transgenic mice

    Tamguney, G; Giles, K; Oehler, A.; Johnson, NL; DeArmond, SJ; Prusiner, SB


    Chronic wasting disease (CWD) of deer and elk is a highly communicable neurodegenerative disorder caused by prions. Investigations of CWD are hampered by slow bioassays in transgenic (Tg) mice. Towards the development of Tg mice that will be more susceptible to CWD prions, we created a series of chimeric elk/mouse transgenes that encode the N terminus of elk PrP (ElkPrP) up to residue Y168 and the C terminus of mouse PrP (MoPrP) beyond residue 169 (mouse numbering), designated Elk3M(SNIVVK). ...

  15. Construction and characterization of chimeric BHIV (BIV/HIV-1) viruses carrying the bovine immunodeficiency virus gag gene

    Zhu, Yi-Xin; Liu, Chang; Liu, Xin-Lei; Qiao, Wen-Tao; Chen, Qi-Min; Zeng, Yi; Geng, Yun-Qi


    AIM: To explore the possibility of the replacement of the gag gene between human immunodeficiency virus and bovine immunodeficiency virus, to achieve chimeric virions, and thereby gain a new kind of AIDS vaccine based on BHIV chimeric viruses.

  16. Authentic display of a cholera toxin epitope by chimeric type 1 fimbriae

    Stentebjerg-Olesen, Bodil; Pallesen, Lars; Jensen, Lars Bogø;


    inserted. Several of the chosen positions seemed amenable even for large foreign inserts; the chimeric proteins were exposed on the bacterial surface and the cholera toxin epitope was authentically displayed, i.e. it was recognized on bacteria by specific antiserum. Display of chimeric fimbriae was tested...

  17. Authentic display of a cholera toxin epitope by chimeric type 1 fimbriae

    Stentebjerg-Olesen, Bodil; Pallesen, Lars; Jensen, Lars Bogø; Christiansen, Gunnar; Klemm, Per

    inserted. Several of the chosen positions seemed amenable even for large foreign inserts; the chimeric proteins were exposed on the bacterial surface and the cholera toxin epitope was authentically displayed, i.e. it was recognized on bacteria by specific antiserum. Display of chimeric fimbriae was tested...

  18. DIVA vaccine properties of the live chimeric pestivirus strain CP7_E2gif

    von Rosen, Tanya; Rangelova, Desislava Yordanova; Nielsen, Jens;


    Live modified vaccines to protect against classical swine fever virus (CSFV), based on chimeric pestiviruses, have been developed to enable serological Differentiation of Infected from Vaccinated Animals (DIVA). In this context, the chimeric virus CP7_E2gif vaccine candidate is unique as it does...

  19. 78 FR 16505 - Prospective Grant of Exclusive License: Chimeric West Nile/Dengue Viruses


    ...: Chimeric West Nile/Dengue Viruses AGENCY: Centers for Disease Control and Prevention (CDC), Department of... license, in the field of use of in vitro diagnostics for dengue virus infection, to practice the... Application 61/049,342, filed 4/30/2008, entitled ``Engineered, Chimeric West Nile/Dengue Viruses;''...

  20. High-resolution air quality simulation over Europe with the chemistry transport model CHIMERE

    E. Terrenoire


    The results suggest that future work should focus on the development of national bottom-up emission inventories including a better account for semi-volatile organic compounds and their conversion to SOA, the improvement of the CHIMERE urban parameterization, the introduction into CHIMERE of the coarse nitrate chemistry and an advanced parameterization accounting for windblown dust emissions.

  1. Homology in Electromagnetic Boundary Value Problems

    Matti Pellikka


    Full Text Available We discuss how homology computation can be exploited in computational electromagnetism. We represent various cellular mesh reduction techniques, which enable the computation of generators of homology spaces in an acceptable time. Furthermore, we show how the generators can be used for setting up and analysis of an electromagnetic boundary value problem. The aim is to provide a rationale for homology computation in electromagnetic modeling software.

  2. Link homology and equivariant gauge theory

    Poudel, Prayat; Saveliev, Nikolai


    The singular instanton Floer homology was defined by Kronheimer and Mrowka in connection with their proof that the Khovanov homology is an unknot detector. We study this theory for knots and two-component links using equivariant gauge theory on their double branched covers. We show that the special generator in the singular instanton Floer homology of a knot is graded by the knot signature mod 4, thereby providing a purely topological way of fixing the absolute grading in the theory. Our appr...

  3. Including Biological Literature Improves Homology Search

    Chang, Jeffrey T.; Raychaudhuri, Soumya; Altman, Russ B


    Annotating the tremendous amount of sequence information being generated requires accurate automated methods for recognizing homology. Although sequence similarity is only one of many indicators of evolutionary homology, it is often the only one used. Here we find that supplementing sequence similarity with information from biomedical literature is successful in increasing the accuracy of homology search results. We modified the PSI-BLAST algorithm to use literature similarity in each iterati...

  4. Deoxyribonucleic Acid Homology Among Lactic Streptococci

    Jarvis, Audrey W.; Jarvis, Brion D. W.


    A comparison was made by deoxyribonucleic acid homology of 45 strains of lactic streptococci, using two strains of Streptococcus cremoris and three strains of Streptococcus lactis as reference strains. All S. cremoris strains were grouped together by deoxyribonucleic acid homology. S. lactis strains formed a second group, except that three strains of S. lactis showed a high degree of homology with S. cremoris strains. The three Streptococcus diacetylactis strains could not be differentiated f...

  5. Homologous Recombination in Negative Sense RNA Viruses

    Michael Worobey; Guan-Zhu Han


    Recombination is an important process that influences biological evolution at many different levels. More and more homologous recombination events have been reported among negative sense RNA viruses recently. While sporadic authentic examples indicate that homologous recombination does occur, recombination seems to be generally rare or even absent in most negative sense RNA viruses, and most of the homologous recombination events reported in the literature were likely generated artificially d...

  6. The Construction of Chimeric T-Cell Receptor with Spacer Base of Modeling Study of VHH and MUC1 Interaction

    Nazanin Pirooznia; Sadegh Hasannia; Majid Taghdir; Fatemeh Rahbarizadeh; Morteza Eskandani


    Adaptive cell immunotherapy with the use of chimeric receptors leads to the best and most specific response against tumors. Chimeric receptors consist of a signaling fragment, extracellular spacer, costimulating domain, and an antibody. Antibodies cause immunogenicity; therefore, VHH is a good replacement for ScFv in chimeric receptors. Since peptide sequences have an influence on chimeric receptors, the effect of peptide domains on each other's conformation were investigated. CD3Zeta, CD28, ...

  7. MHC-mismatched mixed chimerism augments thymic regulatory T-cell production and prevents relapse of EAE in mice

    Wu, Limin; Li, Nainong; Zhang, Mingfeng; XUE, SHENG-LI; Cassady, Kaniel; Lin, Qing; Riggs, Arthur D; Zeng, Defu


    Induction of MHC- or HLA-matched mixed chimerism does not cause graft-versus-host disease (GVHD) in animal models or humans, but matched mixed chimerism cannot reverse autoimmunity. MHC-mismatched mixed chimerism is required for reversal of autoimmunity. Here, we report that, using a clinically applicable conditioning regimen consisting of cyclophosphamide, pentostatin, and antithymocyte globulin, MHC-mismatched mixed chimerism is established in experimental autoimmune encephalomyelitis (EAE)...

  8. 78 FR 13691 - Prospective Grant of Exclusive License: The Development of m971 and m972 Chimeric Antigen...


    ... m971 and m972 Chimeric Antigen Receptors (CARs) for the Treatment of B Cell Malignancies AGENCY... inventions embodied in (a) U.S. Patent Application 61/717,960 entitled ``M971 Chimeric Antigen Receptors... their cell surface using chimeric antigen receptors which contain the m971 or m972 antibody...

  9. Serotype Chimeric Human Adenoviruses for Cancer GeneTherapy

    Akseli Hemminki


    Full Text Available Cancer gene therapy consists of numerous approaches where the common denominator is utilization of vectors for achieving therapeutic effect. A particularly potent embodiment of the approach is virotherapy, in which the replication potential of an oncolytic virus is directed towards tumor cells to cause lysis, while normal cells are spared. Importantly, the therapeutic effect of the initial viral load is amplified through viral replication cycles and production of progeny virions. All cancer gene therapy approaches rely on a sufficient level of delivery of the anticancer agent into target cells. Thus,enhancement of delivery to target cells, and reduction of delivery to non-target cells, in an approach called transductional targeting, is attractive. Both genetic and non-genetic retargeting strategies have been utilized. However, in the context of oncolytic viruses, it is beneficial to have the specific modification included in progeny virions and hence genetic modification may be preferable. Serotype chimerism utilizes serotype specific differences in receptor usage, liver tropism and seroprevalence in order to gain enhanced infection of target tissue. This review will focus on serotype chimeric adenoviruses for cancer gene therapy applications.

  10. Calcium-stimulated autophosphorylation site of plant chimeric calcium/calmodulin-dependent protein kinase

    Sathyanarayanan, P. V.; Siems, W. F.; Jones, J. P.; Poovaiah, B. W.


    The existence of two molecular switches regulating plant chimeric Ca(2+)/calmodulin-dependent protein kinase (CCaMK), namely the C-terminal visinin-like domain acting as Ca(2+)-sensitive molecular switch and calmodulin binding domain acting as Ca(2+)-stimulated autophosphorylation-sensitive molecular switch, has been described (Sathyanarayanan, P. V., Cremo, C. R., and Poovaiah, B. W. (2000) J. Biol. Chem. 275, 30417-30422). Here we report the identification of Ca(2+)-stimulated autophosphorylation site of CCaMK by matrix-assisted laser desorption ionization time of flight-mass spectrometry. Thr(267) was confirmed as the Ca(2+)-stimulated autophosphorylation site by post-source decay experiments and by site-directed mutagenesis. The purified T267A mutant form of CCaMK did not show Ca(2+)-stimulated autophosphorylation, autophosphorylation-dependent variable calmodulin affinity, or Ca(2+)/calmodulin stimulation of kinase activity. Sequence comparison of CCaMK from monocotyledonous plant (lily) and dicotyledonous plant (tobacco) suggests that the autophosphorylation site is conserved. This is the first identification of a phosphorylation site specifically responding to activation by second messenger system (Ca(2+) messenger system) in plants. Homology modeling of the kinase and calmodulin binding domain of CCaMK with the crystal structure of calcium/calmodulin-dependent protein kinase 1 suggests that the Ca(2+)-stimulated autophosphorylation site is located on the surface of the kinase and far from the catalytic site. Analysis of Ca(2+)-stimulated autophosphorylation with increasing concentration of CCaMK indicates the possibility that the Ca(2+)-stimulated phosphorylation occurs by an intermolecular mechanism.

  11. Identification and analysis of pig chimeric mRNAs using RNA sequencing data

    Ma Lei


    Full Text Available Abstract Background Gene fusion is ubiquitous over the course of evolution. It is expected to increase the diversity and complexity of transcriptomes and proteomes through chimeric sequence segments or altered regulation. However, chimeric mRNAs in pigs remain unclear. Here we identified some chimeric mRNAs in pigs and analyzed the expression of them across individuals and breeds using RNA-sequencing data. Results The present study identified 669 putative chimeric mRNAs in pigs, of which 251 chimeric candidates were detected in a set of RNA-sequencing data. The 618 candidates had clear trans-splicing sites, 537 of which obeyed the canonical GU-AG splice rule. Only two putative pig chimera variants whose fusion junction was overlapped with that of a known human chimeric mRNA were found. A set of unique chimeric events were considered middle variances in the expression across individuals and breeds, and revealed non-significant variance between sexes. Furthermore, the genomic region of the 5′ partner gene shares a similar DNA sequence with that of the 3′ partner gene for 458 putative chimeric mRNAs. The 81 of those shared DNA sequences significantly matched the known DNA-binding motifs in the JASPAR CORE database. Four DNA motifs shared in parental genomic regions had significant similarity with known human CTCF binding sites. Conclusions The present study provided detailed information on some pig chimeric mRNAs. We proposed a model that trans-acting factors, such as CTCF, induced the spatial organisation of parental genes to the same transcriptional factory so that parental genes were coordinatively transcribed to give birth to chimeric mRNAs.

  12. The molecular evolution of PL10 homologs

    Chang Ti-Cheng


    Full Text Available Abstract Background PL10 homologs exist in a wide range of eukaryotes from yeast, plants to animals. They share a DEAD motif and belong to the DEAD-box polypeptide 3 (DDX3 subfamily with a major role in RNA metabolism. The lineage-specific expression patterns and various genomic structures and locations of PL10 homologs indicate these homologs have an interesting evolutionary history. Results Phylogenetic analyses revealed that, in addition to the sex chromosome-linked PL10 homologs, DDX3X and DDX3Y, a single autosomal PL10 putative homologous sequence is present in each genome of the studied non-rodent eutheria. These autosomal homologous sequences originated from the retroposition of DDX3X but were pseudogenized during the evolution. In rodents, besides Ddx3x and Ddx3y, we found not only Pl10 but another autosomal homologous region, both of which also originated from the Ddx3x retroposition. These retropositions occurred after the divergence of eutheria and opossum. In contrast, an additional X putative homologous sequence was detected in primates and originated from the transposition of DDX3Y. The evolution of PL10 homologs was under positive selection and the elevated Ka/Ks ratios were observed in the eutherian lineages for DDX3Y but not PL10 and DDX3X, suggesting relaxed selective constraints on DDX3Y. Contrary to the highly conserved domains, several sites with relaxed selective constraints flanking the domains in the mammalian PL10 homologs may play roles in enhancing the gene function in a lineage-specific manner. Conclusion The eutherian DDX3X/DDX3Y in the X/Y-added region originated from the translocation of the ancient PL10 ortholog on the ancestral autosome, whereas the eutherian PL10 was retroposed from DDX3X. In addition to the functional PL10/DDX3X/DDX3Y, conserved homologous regions on the autosomes and X chromosome are present. The autosomal homologs were also derived from DDX3X, whereas the additional X-homologs were derived

  13. Homotopic Chain Maps Have Equal s-Homology and d-Homology

    M. Z. Kazemi-Baneh


    Full Text Available The homotopy of chain maps on preabelian categories is investigated and the equality of standard homologies and d-homologies of homotopic chain maps is established. As a special case, if X and Y are the same homotopy type, then their nth d-homology R-modules are isomorphic, and if X is a contractible space, then its nth d-homology R-modules for n≠0 are trivial.

  14. Invariants and structures of the homology cobordism group of homology cylinders

    Song, Minkyoung


    The homology cobordism group of homology cylinders is a generalization of the mapping class group and the string link concordance group. We study this group and its filtrations by subgroups by developing new homomorphisms. First, we define extended Milnor invariants by combining the ideas of Milnor's link invariants and Johnson homomorphisms. They give rise to a descending filtration of the homology cobordism group of homology cylinders. We show that each successive quotient of the filtration...

  15. Novel Chimeric β-Lactamase CTX-M-64, a Hybrid of CTX-M-15-Like and CTX-M-14 β-Lactamases, Found in a Shigella sonnei Strain Resistant to Various Oxyimino-Cephalosporins, Including Ceftazidime▿

    Nagano, Yukiko; Nagano, Noriyuki; Wachino, Jun-ichi; Ishikawa, Keiko; Arakawa, Yoshichika


    The plasmid-mediated novel β-lactamase CTX-M-64 was first identified in Shigella sonnei strain UIH-1, which exhibited resistance to cefotaxime (MIC, 1,024 μg/ml) and ceftazidime (MIC, 32 μg/ml). The amino acid sequence of CTX-M-64 showed a chimeric structure of a CTX-M-15-like β-lactamase (N- and C-terminal moieties) and a CTX-M-14-like β-lactamase (central portion, amino acids 63 to 226), suggesting that it originated by homologous recombination between the corresponding genes. The introduct...

  16. Buoyancy instability of homologous implosions

    Johnson, Bryan


    Hot spot turbulence is a potential contributor to yield degradation in inertial confinement fusion (ICF) capsules, although its origin, if present, remains unclear. In this work, a perturbation analysis is performed of an analytical homologous solution that mimics the hot spot and surrounding cold fuel during the late stages of an ICF implosion. It is shown that the flow is governed by the Schwarzschild criterion for buoyant stability, and that during stagnation, short wavelength entropy and vorticity fluctuations amplify by a factor exp (π |N0 | ts) , where N0 is the buoyancy frequency at stagnation and ts is the stagnation time scale. This amplification factor is exponentially sensitive to mean flow gradients and varies from 103-107 for realistic gradients. Comparisons are made with a Lagrangian hydrodynamics code, and it is found that a numerical resolution of ~ 30 zones per wavelength is required to capture the evolution of vorticity accurately. This translates to an angular resolution of ~(12 / l) ∘ , or ~ 0 .1° to resolve the fastest growing modes (Legendre mode l > 100).

  17. Buoyancy instability of homologous implosions

    Johnson, Bryan M


    I consider the hydrodynamic stability of imploding gases as a model for inertial confinement fusion capsules, sonoluminescent bubbles and the gravitational collapse of astrophysical gases. For oblate modes under a homologous flow, a monatomic gas is governed by the Schwarzschild criterion for buoyant stability. Under buoyantly unstable conditions, fluctuations experience power-law growth in time, with a growth rate that depends upon mean flow gradients and is independent of mode number. If the flow accelerates throughout the implosion, oblate modes amplify by a factor (2C)^(|N0| ti)$, where C is the convergence ratio of the implosion, N0 is the initial buoyancy frequency and ti is the implosion time scale. If, instead, the implosion consists of a coasting phase followed by stagnation, oblate modes amplify by a factor exp(pi |N0| ts), where N0 is the buoyancy frequency at stagnation and ts is the stagnation time scale. Even under stable conditions, vorticity fluctuations grow due to the conservation of angular...

  18. Stability of p53 homologs.

    Tobias Brandt

    Full Text Available Most proteins have not evolved for maximal thermal stability. Some are only marginally stable, as for example, the DNA-binding domains of p53 and its homologs, whose kinetic and thermodynamic stabilities are strongly correlated. Here, we applied high-throughput methods using a real-time PCR thermocycler to study the stability of several full-length orthologs and paralogs of the p53 family of transcription factors, which have diverse functions, ranging from tumour suppression to control of developmental processes. From isothermal denaturation fluorimetry and differential scanning fluorimetry, we found that full-length proteins showed the same correlation between kinetic and thermodynamic stability as their isolated DNA-binding domains. The stabilities of the full-length p53 orthologs were marginal and correlated with the temperature of their organism, paralleling the stability of the isolated DNA-binding domains. Additionally, the paralogs p63 and p73 were significantly more stable and long-lived than p53. The short half-life of p53 orthologs and the greater persistence of the paralogs may be biologically relevant.

  19. Products and relations in symplectic Floer homology

    Betz, Marty; Rade, Johan


    We give a construction of a version of the Gromov-Witten classes, Q: H_*(J) -> HF_*(M) otimes ... otimes HF^*(M), within the context of symplectic Floer (co)homology. In particular, this gives a functorial approach to products and relations in symplectic Floer (co)homology.

  20. On the computation of torus link homology

    Elias, Ben; Hogancamp, Matthew


    We introduce a new method for computing triply graded link homology, which is particularly well-adapted to torus links. Our main application is to the (n,n)-torus links, for which we give an exact answer for all n. In several cases, our computations verify conjectures of Gorsky et al relating homology of torus links with Hilbert schemes.

  1. MIF proteins are not glutathione transferase homologs.

    Pearson, W R


    Although macrophage migration inhibitory factor (MIF) proteins conjugate glutathione, sequence analysis does not support their homology to other glutathione transferases. Glutathione transferases are not detected with MIF proteins in searches of protein sequence databases, and MIF proteins do not share significant sequence similarity with glutathione transferases. Homology cannot be demonstrated by multiple sequence alignment or evolutionary tree construction; such methods assume that the pro...

  2. Matroid Filtrations and Computational Persistent Homology

    Henselman, Gregory; Ghrist, Robert


    This technical report introduces a novel approach to efficient computation in homological algebra over fields, with particular emphasis on computing the persistent homology of a filtered topological cell complex. The algorithms here presented rely on a novel relationship between discrete Morse theory, matroid theory, and classical matrix factorizations. We provide background, detail the algorithms, and benchmark the software implementation in the Eirene package.

  3. Equivariant symplectic homology of Anosov contact structures

    Macarini, Leonardo


    We show that the differential in positive equivariant symplectic homology or linearized contact homology vanishes for non-degenerate Reeb flows with a continuous invariant Lagrangian subbundle (e.g. Anosov Reeb flows). Several applications are given, including obstructions to the existence of these flows and abundance of periodic orbits for contact forms representing an Anosov contact structure.

  4. Construction and characterization of chimeric BHIV (BIV/HIV-1) viruses carrying the bovine immunodeficiency virus gag gene

    Yi-Xin Zhu; Chang Liu; Xin-Lei Liu; Wen-Tao Qiao; Qi-Min Chen; Yi Zeng; Yun-Qi Geng


    AIM: To explore the possibility of the replacement of the gag gene between human immunodeficiency virus and bovine immunodeficiency virus, to achieve chimeric virions,and thereby gain a new kind of AIDS vaccine based on BHIV chimeric viruses.METHODS: A series of chimeric BHIV proviral DNAs differing in the replacement regions in gag gene were constructed, and then were transfected into 293T cells. The expression of chimeric viral genes was detected at the RNA and protein level. The supematant of 293T cell was ultra centrifuged to detect the probable chimeric virion. Once the chimeric virion was detected, its biological activities were also assayed by infecting HIV-sensitive MT4 cells.RESULTS: Four chimeric BHIV proviral DNAs were constructed. Genes in chimeric viruses expressed correctly in transfected 293T cells. All four constructs assembled chimeric virions with different degrees of efficiency. These virions had complete structures common to retroviruses and packaged genomic RNAs, but the cleavages of the precursor Gag proteins were abnormal to some extent. Three of these virions tested could attach and enter into MT4 cells, and one of them could complete the course of reverse transcription. Yet none of them could replicate in MT4 cells.CONCLUSION: The replacement of partial gag gene of HIV with BIV gaggene is feasible. Genes in chimeric BHIVs are accurately expressed, and virions are assembled. These chimeric BHIVs (proviral DNA together with virus particles) have the potential to become a new kind of HIV/AIDS vaccine.

  5. Modeling cognition and disease using human glial chimeric mice

    Goldman, Steven A.; Nedergaard, Maiken; Windrem, Martha S.


    cognition and information processing. In addition, the cellular humanization of these brains permits their use in studying glial infectious and inflammatory disorders unique to humans, and the effects of those disorders on the glial contributions to cognition. Perhaps most intriguingly, by pairing our...... ability to construct human glial chimeras with the production of patient-specific hGPCs derived from pluripotential stem cells, we may now establish mice in which a substantial proportion of resident glia are both human and disease-derived. These mice in particular may provide us new opportunities for...... studying the human-specific contributions of glia to psychopathology, as well as to higher cognition. As such, the assessment of human glial chimeric mice may provide us new insight into the species-specific contributions of glia to human cognitive evolution, as well as to the pathogenesis of human...

  6. Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy.

    Dai, Hanren; Wang, Yao; Lu, Xuechun; Han, Weidong


    The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy. PMID:26819347

  7. Confined Blood Chimerism in Monochorionic Dizygotic Twins Conceived Spontaneously

    Takashi Kanda


    Full Text Available Traditionally, monochorionicity has been regarded as synonymous with monozygosity. However, several recent cases of monochorionic dizygotic twins have shown that monochorionic twins can be dizygous. We report a rare case of monochorionic diamnionic, gender-discordant twins who were conceived spontaneously. Initially, a monochorionic placenta was diagnosed by ultrasonography at 8 weeks of gestation and then confirmed by pathology after delivery. The twins had different genders. A comparison of cytogenetic analyses using peripheral blood lymphocytes and skin fibroblasts revealed that chimerism was confined to blood cells. We have experienced two cases of monochorionic dizygotic twins since 2003. These cases suggest that monochorionic dizygotic twins are not as rare as previously thought.

  8. Persistence of chicken herpesvirus and retroviral chimeric molecules upon in vivo passage.

    Borenshtain, R; Witter, R L; Davidson, I


    Mareks disease virus (MDV), a herpesvirus, and avian leucosis virus subgroup J (ALV-J), a retrovirus, were used for experimental coinfection of chickens. Chimeric molecules having sequences of both viruses were detected by the hotspot-combined polymerase chain reaction (HS-cPCR) system. The detection of chimeric molecules provided evidence for avian retroviral inserts in the herpesvirus genome. The persistence of chimeric molecules on in vivo passage served to indicate the infectivity of the recombinant virus. The evaluation of formation and persistence of the chimeric molecules was performed in two trials involving three in vivo passages. The chimeric molecules were identified according to the primer sets, their product length, and pattern. The persistence of chimeric molecules on in vivo passages served as an indication of their ability to replicate in and infect chickens. In the first experimental passage, MDV and ALV-J prototype strains, MD11 and HC-1, were intraperitoneally (i.p.) injected into 1-day-old chicks. The second trial included two passages. Passage II chicks were injected i.p. and passage III chickens were in contact with the chickens of passage II. For passage II, enriched white blood cells from blood samples of chickens from the first trial that had chimeric molecules were injected i.p. into 1-day-old chicks. For passage III, uninfected chicks were included together with the infected chicks. Synthesis evidence for the various species of chimeric molecules was assessed in the tissues of birds of the second trial. DNA was extracted from blood and feathers and analyzed by the hotspot-combined PCR and by pulsed field gel electrophoresis. To overcome the limits of detection, three amplification assays followed by hybridization of the products to specific viral probes were conducted. A variety of chimeric molecules were detected in low concentrations. Five species of chimeric molecules were characterized in blood, tumors, and feathers. Chimeric

  9. Threading homology through algebra selected patterns

    Boffi, Giandomenico


    Aimed at graduate students and researchers in mathematics, this book takes homological themes, such as Koszul complexes and their generalizations, and shows how these can be used to clarify certain problems in selected parts of algebra, as well as their success in solving a number of them. - ;Threading Homology through Algebra takes homological themes (Koszul complexes and their variations, resolutions in general) and shows how these affect the perception of certain problems in selected parts of algebra, as well as their success in solving a number of them. The text deals with regular local ri

  10. Chimeric relaxin peptides highlight the role of the A-chain in the function of H2 relaxin.

    Hossain, Mohammed Akhter; Wade, John D; Bathgate, Ross A D


    Human gene-2 (H2) relaxin is a member of the insulin-relaxin peptide superfamily. Because of the potential clinical applications of H2 relaxin, there is a need for novel analogs that have improved biological activity and receptor specificity. In this respect, we have chemically assembled chimeric peptides consisting of the B-chain of H2 relaxin in combination with A-chains from other insulin/relaxin family members. The peptides were prepared using solid phase peptide synthesis together with regioselective disulfide bond formation and characterized by RP-HPLC, MALDI-TOF MS and amino acid analysis. Their in vitro activity was assessed in RXFP1 or RXFP2 expressing cells. Replacement of the H2 relaxin A-chain resulted in parallel losses of binding affinity and activity on RXFP1. Not surprisingly H1A-H2B demonstrated the highest activity as the H1 A-chain shares high homology with H2 relaxin whereas INSLA-H2B, which shows low homology, had very poor activity. Importantly A-chain replacements had a dramatic effect on RXFP2 activity similar to previous results demonstrating different modes of activation of A-chain variants on RXFP1 and RXFP2. H3A-H2B is particularly interesting as it displays moderate activity at RXFP1 but poor activity at RXFP2 indicating that it may be a template for specific RXFP1 agonist development. Our study confirms that the activity of H2 relaxin at both RXFP1 and RXFP2 relies on interactions with both the B- and A-chains, and also provide new biochemical insights into the mechanism of relaxin action that the A-chain needs to be in native or near-native form for strong RXFP1 or RXFP2 agonist activity. PMID:22414484

  11. Superconformal field theories and cyclic homology

    Eager, Richard


    One of the predictions of the AdS/CFT correspondence is the matching of protected operators between a superconformal field theory and its holographic dual. We review the spectrum of protected operators in quiver gauge theories that flow to superconformal field theories at low energies. The spectrum is determined by the cyclic homology of an algebra associated to the quiver gauge theory. Identifying the spectrum of operators with cyclic homology allows us to apply the Hochschild-Kostant-Rosenberg theorem to relate the cyclic homology groups to deRham cohomology groups. The map from cyclic homology to deRham cohomology can be viewed as a mathematical avatar of the passage from open to closed strings under the AdS/CFT correspondence.

  12. Exceptional cosmetic surgeries on homology spheres

    Ravelomanana, Huygens C.


    We investigate the cosmetic surgery conjecture for hyperbolic knots in integer homology spheres, focusing on exceptional surgeries. We give some restrictions on the slopes of exceptional truly cosmetic surgeries according to the type of surgery.

  13. A chimeric measles virus with a lentiviral envelope replicates exclusively in CD4+/CCR5+ cells

    We generated a replicating chimeric measles virus in which the hemagglutinin and fusion surface glycoproteins were replaced with the gp160 envelope glycoprotein of simian immunodeficiency virus (SIVmac239). Based on a previously cloned live-attenuated Schwarz vaccine strain of measles virus (MV), this chimera was rescued at high titers using reverse genetics in CD4+ target cells. Cytopathic effect consisted in the presence of large cell aggregates evolving to form syncytia, as observed during SIV infection. The morphology of the chimeric virus was identical to that of the parent MV particles. The presence of SIV gp160 as the only envelope protein on chimeric particles surface altered the cell tropism of the new virus from CD46+ to CD4+ cells. Used as an HIV candidate vaccine, this MV/SIVenv chimeric virus would mimic transient HIV-like infection, benefiting both from HIV-like tropism and the capacity of MV to replicate in dendritic cells, macrophages and lymphocytes.

  14. Cylindrical contact homology and topological entropy

    Alves, Marcelo R. R.


    We establish a relation between the growth of the cylindrical contact homology of a contact manifold and the topological entropy of Reeb flows on this manifold. We show that if a contact manifold $(M,\\xi)$ admits a hypertight contact form $\\lambda_0$ for which the cylindrical contact homology has exponential homotopical growth rate, then the Reeb flow of every contact form on $(M,\\xi)$ has positive topological entropy. Using this result, we provide numerous new examples of contact 3-manifolds...

  15. Dualities in Persistent (Co)Homology

    de Silva, Vin; Morozov, Dmitriy; Vejdemo-Johansson, Mikael


    We consider sequences of absolute and relative homology and cohomology groups that arise naturally for a filtered cell complex. We establishalgebraic relationships between their persistence modules, and show that they contain equivalent information. We explain how one can use the existingalgorithm for persistent homology to process any of the four modules, and relate it to a recently introduced persistent cohomology algorithm. Wepresent experimental evidence for the practical efficiency of the latter algorithm.

  16. Quantitative chimerism kinetics in relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation

    QIN Xiao-ying; WANG Jing-zhi; ZHANG Xiao-hui; LI Jin-lan; LI Ling-di; LIU Kai-yan; HUANG Xiao-jun; LI Guo-xuan; QIN Ya-zhen; WANG Yu; WANG Feng-rong; LIU Dai-hong; XU Lan-ping; CHEN Huan; HAN Wei


    Background Chimerism analysis is an important tool for the surveillance of post-transplant engraftment.It offers the possibility of identifying impending graft rejection and recurrence of underlying malignant or non-malignant disease.Here we investigated the quantitative chimerism kinetics of 21 relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation (HSCT).Methods A panel of 29 selected sequence polymorphism (SP) markers was screened by real-time polymerase chain reaction (RT-PCR) to obtain the informative marker for every leukemia patient.Quantitative chimerism analysis of bone marrow (BM) samples of 21 relapsed patients and 20 patients in stable remission was performed longitudinally.The chimerisms of BM and peripheral blood (PB) samples of 14 patients at relapse were compared.Results Twenty-one patients experienced leukemia relapse at a median of 135 days (range,30-720 days) after transplantation.High recipient chimerism in BM was found in all patients at relapse,and increased recipient chimerism in BM samples was observed in 90% (19/21) of patients before relapse.With 0.5% recipient DNA as the cut-off,median time between the detection of increased recipient chimerism and relapse was 45 days (range,0-120 days),with 76% of patients showing increased recipient chimerism at least 1 month prior to relapse.Median percentage of recipient DNA in 20 stable remission patients was 0.28%,0.04%,0.05%,0.05%,0.08%,and 0.05% at 1,2,3,6,9,and 12 months,respectively,after transplantation.This was concordant with other specific fusion transcripts and fluorescent in situ hybridization examination.The recipient chimerisms in BM were significantly higher than those in PB at relapse (P=0.001).Conclusions This SP-based RT-PCR essay is a reliable method for chimerism analysis.Chimerism kinetics in BM can be used as a marker of impending leukemia relapse,especially when no other specific marker is available.Based on our findings

  17. On the hodological criterion for homology

    Faunes, Macarena; Francisco Botelho, João; Ahumada Galleguillos, Patricio; Mpodozis, Jorge


    Owen's pre-evolutionary definition of a homolog as “the same organ in different animals under every variety of form and function” and its redefinition after Darwin as “the same trait in different lineages due to common ancestry” entail the same heuristic problem: how to establish “sameness.”Although different criteria for homology often conflict, there is currently a generalized acceptance of gene expression as the best criterion. This gene-centered view of homology results from a reductionist and preformationist concept of living beings. Here, we adopt an alternative organismic-epigenetic viewpoint, and conceive living beings as systems whose identity is given by the dynamic interactions between their components at their multiple levels of composition. We posit that there cannot be an absolute homology criterion, and instead, homology should be inferred from comparisons at the levels and developmental stages where the delimitation of the compared trait lies. In this line, we argue that neural connectivity, i.e., the hodological criterion, should prevail in the determination of homologies between brain supra-cellular structures, such as the vertebrate pallium. PMID:26157357

  18. Chimeric hepatitis B virus core particles as probes for studying peptide-integrin interactions.

    Chambers, M A; Dougan, G; Newman, J.; Brown, F.; Crowther, J.; Mould, A P; Humphries, M J; Francis, M. J.; Clarke, B.; Brown, A L; Rowlands, D.


    An RGD-containing epitope from the foot-and-mouth disease virus (FMDV) VP1 protein was inserted into the e1 loop of the hepatitis B virus core (HBc) protein. This chimeric protein was expressed at high levels in Escherichia coli and spontaneously assembled into virus-like particles which could be readily purified. These fusion particles elicited high levels of both enzyme-linked immunosorbent assay- and FMDV-neutralizing antibodies in guinea pigs. The chimeric particles bound specifically to ...

  19. Assembling Single-Cell Genomes and Mini-Metagenomes From Chimeric MDA Products

    Nurk, Sergey; Bankevich, Anton; Antipov, Dmitry; Gurevich, Alexey A.; Korobeynikov, Anton; Lapidus, Alla; Prjibelski, Andrey D.; Pyshkin, Alexey; Sirotkin, Alexander; Sirotkin, Yakov; Stepanauskas, Ramunas; Clingenpeel, Scott R.; Woyke, Tanja; Jeffrey S. McLean; Lasken, Roger


    Recent advances in single-cell genomics provide an alternative to largely gene-centric metagenomics studies, enabling whole-genome sequencing of uncultivated bacteria. However, single-cell assembly projects are challenging due to (i) the highly nonuniform read coverage and (ii) a greatly elevated number of chimeric reads and read pairs. While recently developed single-cell assemblers have addressed the former challenge, methods for assembling highly chimeric reads remain poorly explored. We p...

  20. Hematopoietic Chimerism Monitoring Based on STRs: Quantitative Platform Performance on Sequential Samples

    Kristt, Don; Israeli, Moshe; Narinski, Ronit; Or, Hagit; Yaniv, I; Stein, Jerry; Klein, Tirza


    Hematopoietic stem cell transplantation (HSCT) creates a donor-recipient cellular chimerism in the patient, which is quantitatively assayed from peripheral blood based on STR-DNA. Since chimerism values often vary across a patient’s samples, it is important to determine to what extent this variability reflects technical aspects of platform performance. This issue is systematically assessed in the current study for the first time. Using the SGM Plus multiplex PCR kit and ABI platform, the long...

  1. Context Dependent Effects of Chimeric Peptide Morpholino Conjugates Contribute to Dystrophin Exon-skipping Efficiency

    Yin, HaiFang; Boisguerin, Prisca; Moulton, Hong M.; Betts, Corinne; Seow, Yiqi; Boutilier, Jordan; Wang, Qingsong; Walsh, Anthony; Lebleu, Bernard; Wood, Matthew JA


    We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. In the present study, the general mechanistic significance of the chimeric peptide configuration on the activity and tissue uptake of peptide conjugated PMOs in vivo was ...

  2. Targeting duplex DNA with chimeric α,β-triplex-forming oligonucleotides

    Kolganova, N. A.; Shchyolkina, A K; Chudinov, A. V.; Zasedatelev, A S; Florentiev, V L; Timofeev, E. N.


    Triplex-directed DNA recognition is strictly limited by polypurine sequences. In an attempt to address this problem with synthetic biology tools, we designed a panel of short chimeric α,β-triplex-forming oligonucleotides (TFOs) and studied their interaction with fluorescently labelled duplex hairpins using various techniques. The hybridization of hairpin with an array of chimeric probes suggests that recognition of double-stranded DNA follows complicated rules combining reversed Hoogsteen and...

  3. Mosaic origins of a complex chimeric mitochondrial gene in Silene vulgaris.

    Helena Storchova

    Full Text Available Chimeric genes are significant sources of evolutionary innovation that are normally created when portions of two or more protein coding regions fuse to form a new open reading frame. In plant mitochondria astonishingly high numbers of different novel chimeric genes have been reported, where they are generated through processes of rearrangement and recombination. Nonetheless, because most studies do not find or report nucleotide variation within the same chimeric gene, evolution after the origination of these chimeric genes remains unstudied. Here we identify two alleles of a complex chimera in Silene vulgaris that are divergent in nucleotide sequence, genomic position relative to other mitochondrial genes, and expression patterns. Structural patterns suggest a history partially influenced by gene conversion between the chimeric gene and functional copies of subunit 1 of the mitochondrial ATP synthase gene (atp1. We identified small repeat structures within the chimeras that are likely recombination sites allowing generation of the chimera. These results establish the potential for chimeric gene divergence in different plant mitochondrial lineages within the same species. This result contrasts with the absence of diversity within mitochondrial chimeras found in crop species.

  4. Prognostic Utility of Routine Chimerism Testing at 2 – 6 Months after Allogeneic Hematopoietic Cell Transplantation

    Mossallam, Ghada I.; Kamel, Azza M.; Storer, Barry; Martin, Paul J.


    The utility of routine chimerism analysis as a prognostic indicator of subsequent outcomes after allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning regimens remains controversial. To address this controversy, routine chimerism test results at 2 – 6 months after HCT with myeloablative conditioning regimens were evaluated for association with subsequent risks of chronic graft versus host disease (GVHD), non-relapse mortality (NRM), relapse and overall mortality. Only 70 (5%) of 1304 patients had <95% donor-derived cells in the marrow. Low donor chimerism in the marrow occurred predominantly among patients with low risk disease as compared to higher risk diseases and was significantly associated with a reduced risk of chronic GVHD. Among 673 patients tested, 164 (24%) had <85% donor-derived T cells in the blood. Low donor T cell chimerism occurred predominantly among patients with low risk disease as compared to higher risk diseases, among those who had conditioning with busulfan as compared to TBI, and among those with lower grades of acute GVHD. Low donor T cell chimerism in the blood was significantly associated with a reduced risk of chronic GVHD, but not with the risks of relapse, NRM or overall mortality. Routine testing of chimerism in the marrow and blood at 2 – 6 months after HCT with myeloablative conditioning regimens may be helpful in documenting engraftment in clinical trials but provides only limited prognostic information in clinical practice. PMID:19203726

  5. Investigating homology between proteins using energetic profiles.

    James O Wrabl


    Full Text Available Accumulated experimental observations demonstrate that protein stability is often preserved upon conservative point mutation. In contrast, less is known about the effects of large sequence or structure changes on the stability of a particular fold. Almost completely unknown is the degree to which stability of different regions of a protein is generally preserved throughout evolution. In this work, these questions are addressed through thermodynamic analysis of a large representative sample of protein fold space based on remote, yet accepted, homology. More than 3,000 proteins were computationally analyzed using the structural-thermodynamic algorithm COREX/BEST. Estimated position-specific stability (i.e., local Gibbs free energy of folding and its component enthalpy and entropy were quantitatively compared between all proteins in the sample according to all-vs.-all pairwise structural alignment. It was discovered that the local stabilities of homologous pairs were significantly more correlated than those of non-homologous pairs, indicating that local stability was indeed generally conserved throughout evolution. However, the position-specific enthalpy and entropy underlying stability were less correlated, suggesting that the overall regional stability of a protein was more important than the thermodynamic mechanism utilized to achieve that stability. Finally, two different types of statistically exceptional evolutionary structure-thermodynamic relationships were noted. First, many homologous proteins contained regions of similar thermodynamics despite localized structure change, suggesting a thermodynamic mechanism enabling evolutionary fold change. Second, some homologous proteins with extremely similar structures nonetheless exhibited different local stabilities, a phenomenon previously observed experimentally in this laboratory. These two observations, in conjunction with the principal conclusion that homologous proteins generally conserved

  6. Protective and immunological behavior of chimeric yellow fever dengue vaccine.

    Halstead, Scott B; Russell, Philip K


    Clinical observations from the third year of the Sanofi Pasteur chimeric yellow fever dengue tetravalent vaccine (CYD) trials document both protection and vaccination-enhanced dengue disease among vaccine recipients. Children who were 5 years-old or younger when vaccinated experienced a DENV disease resulting in hospitalization at 5 times the rate of controls. On closer inspection, hospitalized cases among vaccinated seropositives, those at highest risk to hospitalized disease accompanying a dengue virus (DENV) infection, were greatly reduced by vaccination. But, seronegative individuals of all ages after being vaccinated were only modestly protected from mild to moderate disease throughout the entire observation period despite developing neutralizing antibodies at high rates. Applying a simple epidemiological model to the data, vaccinated seronegative individuals of all ages were at increased risk of developing hospitalized disease during a subsequent wild type DENV infection. The etiology of disease in placebo and vaccinated children resulting in hospitalization during a DENV infection, while clinically similar are of different origin. The implications of the observed mixture of DENV protection and enhanced disease in CYD vaccinees are discussed. PMID:26873054

  7. Toxicities of chimeric antigen receptor T cells: recognition and management.

    Brudno, Jennifer N; Kochenderfer, James N


    Chimeric antigen receptor (CAR) T cells can produce durable remissions in hematologic malignancies that are not responsive to standard therapies. Yet the use of CAR T cells is limited by potentially severe toxicities. Early case reports of unexpected organ damage and deaths following CAR T-cell therapy first highlighted the possible dangers of this new treatment. CAR T cells can potentially damage normal tissues by specifically targeting a tumor-associated antigen that is also expressed on those tissues. Cytokine release syndrome (CRS), a systemic inflammatory response caused by cytokines released by infused CAR T cells can lead to widespread reversible organ dysfunction. CRS is the most common type of toxicity caused by CAR T cells. Neurologic toxicity due to CAR T cells might in some cases have a different pathophysiology than CRS and requires different management. Aggressive supportive care is necessary for all patients experiencing CAR T-cell toxicities, with early intervention for hypotension and treatment of concurrent infections being essential. Interleukin-6 receptor blockade with tocilizumab remains the mainstay pharmacologic therapy for CRS, though indications for administration vary among centers. Corticosteroids should be reserved for neurologic toxicities and CRS not responsive to tocilizumab. Pharmacologic management is complicated by the risk of immunosuppressive therapy abrogating the antimalignancy activity of the CAR T cells. This review describes the toxicities caused by CAR T cells and reviews the published approaches used to manage toxicities. We present guidelines for treating patients experiencing CRS and other adverse events following CAR T-cell therapy. PMID:27207799

  8. Dosimetry of chimeric TNT in lung tumor patients

    CHEN Yangchun; CHEN Shaoliang; JU Dianwen; SHI Hongcheng; YAO Zhifeng


    The purpose of this study was to assess the absorbed dose of tumor and main critical organs in 131I labeled chimeric tumor necrotic treatment (chTNT). In 9 patients, a single intravenous dose of (29.6±3.7) MBq/kg was administered. Blood samples were drawn at different time intervals, and urine was collected for up to one week. Tissue distribution of 131I -chTNT was followed for up to one week by gamma camera imaging. Absorbed doses to the whole body and to normal organs were computed according to the MIRD scheme using Mirdose-3 software. S-factors for lung tumors were estimated by comparison with lungs of similar mass and position in the body. It was found that mean serum disappearance half time values for 131I-chTNT were (4.93±9.36) h and (61.7±21.2) h for α, β respectively,while that for whole body was(99±10) h. Mean urine biological clearance half time value was (90±10) h. The absorbed dose to tumor was (8.28±2.65) Gy, and the tumor-to-nontumor dose ratio was 3.95±1.55. And the mean effective dose to patients was (1.02±0.29) mSv/MBq.

  9. Development of chimeric antigen receptors for multiple myeloma.

    Martínez-Cingolani, Carolina; Bories, Jean Christophe


    Multiple myeloma (MM) is a haematologic malignancy characterized by the expansion of monoclonal plasma cells in the bone marrow. It is associated with serum or urine monoclonal protein and organ damage including renal failure, anaemia, hypercalcaemia and bone lesions. Despite recent improvements MM still remains an incurable disease. Previous studies have shown that the adoptive transfer of autologous T-cells modified to express chimeric antigen receptors (CAR) is effective in cases of acute and chronic lymphoid leukaemia. However, the adjustment of CAR-T-cell therapy to MM is hindered by the scarcity of antigens specific to the tumour plasma cells. Most candidate targets are shared by healthy tissues, and entail high risks of toxicity. Therefore several strategies have been proposed to regulate CAR-T-cell function as well as to enhance CAR-T-cell specificity against tumour cells. In this article we summarize the surface markers that have been investigated as targets to eliminate MM plasma cells and the MM-specific CARs that have been developed to date. Then we describe the different CAR-T-cell designs that could be applied in the case of MM to circumvent current problems of toxicity. PMID:27068946

  10. Dosimetry of chimeric TNT in lung tumor patients

    The purpose of this study was to assess the absorbed dose of tumor and main critical organs in 131I labeled chimeric tumor necrotic treatment (chTNT). In 9 patients, a single intravenous dose of (29.6±3.7) MBq/kg was administered. Blood samples were drawn at different time intervals, and urine was collected for up to one week. Tissue distribution of 131I -chTNT was followed for up to one week by gamma camera imaging. Absorbed doses to the whole body and to normal organs were computed according to the MIRD scheme using Mirdose-3 software. S-factors for lung tumors were estimated by comparison with lungs of similar mass and position in the body. It was found that mean serum disappearance half time values for 131I-chTNT were (4.934±9.36) h and (61.74±21.2) h for α, β respectively, while that for whole body was(99±10) h. Mean urine biological clearance half time value was (90±10) h. The ab- sorbed dose to tumor was (8.28±2.65) Gy, and the tumor-to-nontumor dose ratio was 3.95±1.55. And the mean effective dose to patients was (1.02±0.29) mSv/MBq. (authors)

  11. On the hodological criterion for homology

    Macarena eFaunes


    Full Text Available Owen’s pre-evolutionary definition of a homologue as the same organ in different animals under every variety of form and function and its redefinition after Darwin as the same trait in different lineages due to common ancestry entail the same heuristic problem: how to establish sameness. Although different criteria for homology often conflict, there is currently a generalized acceptance of gene expression as the best criterion. This gene-centered view of homology results from a reductionist and preformationist concept of living beings. Here, we adopt an alternative organismic-epigenetic viewpoint, and conceive living beings as systems whose identity is given by the dynamic interactions between their components at their multiple levels of composition. We posit that there cannot be an absolute homology criterion, and instead, homology should be inferred from comparisons at the levels and developmental stages where the delimitation of the compared trait lies. In this line, we argue that neural connectivity, i.e., the hodological criterion, should prevail in the determination of homologies between brain supra-cellular structures, such as the vertebrate pallium.

  12. Immunological tolerance and tumor rejection in embryo-aggregated chimeric mice – Lessons for tumor immunity

    Rejection of transplanted tumors by the immune system is a rare event in syngeneic hosts, and is considered to be dependent on the local interaction of defensive immune reactions and tumor tolerance mechanisms. Here, we have enlisted the aid of a unique set of embryo-aggregated lineage chimeric mice derived from C57/BL6 and FVB donors to study the interplay between local and systemic tumor immunity and tolerance in rejection of mouse B16 melanoma cells, syngeneic to the C57/BL6 donor strain. Two variants of embryo-aggregated chimeric mice with either variable or no contribution of C57-derived cells to their skin were generated by the fusion of different ratios of morula stage blastomers. Chimeric mice were analyzed for s.c. growth of B16 tumors in comparison to their respective donor strains as well as normal F1 hybrids, and the relative frequencies of cellular components of the immune system by FACS analysis of peripheral blood or lymph node cells. B16 tumors grew significantly faster in mice with full chimerism in their skin as compared to syngeneic C57 or semi-syngeneic C57 × FVB F1 hosts. In contrast, s.c. tumor growth was either absent or significantly reduced in chimeric mice lacking C57-derived cells in their skin, but tolerant to C57 tissue in other organs. Comparison of the relative frequencies of various immune cells in the periphery via FACS-analysis did not reveal any significant differences between the two types of chimeric mice with respect to their donor strains. Our data suggest a complex interplay between mechanisms of local peripheral tolerance and innate antitumor mechanisms possibly involving NK cell allorecognition as a basis for the differential growth or rejection of B16 tumors in these unique chimeric mice, which we suggest to constitute a valuable new model system for the study of immune-mediated tumor rejection

  13. Antigenic properties of a transport-competent influenza HA/HIV Env chimeric protein

    The transmembrane subunit (gp41) of the HIV Env glycoprotein contains conserved neutralizing epitopes which are not well-exposed in wild-type HIV Env proteins. To enhance the exposure of these epitopes, a chimeric protein, HA/gp41, in which the gp41 of HIV-1 89.6 envelope protein was fused to the C-terminus of the HA1 subunit of the influenza HA protein, was constructed. Characterization of protein expression showed that the HA/gp41 chimeric proteins were expressed on cell surfaces and formed trimeric oligomers, as found in the HIV Env as well as influenza HA proteins. In addition, the HA/gp41 chimeric protein expressed on the cell surface can also be cleaved into 2 subunits by trypsin treatment, similar to the influenza HA. Moreover, the HA/gp41 chimeric protein was found to maintain a pre-fusion conformation. Interestingly, the HA/gp41 chimeric proteins on cell surfaces exhibited increased reactivity to monoclonal antibodies against the HIV Env gp41 subunit compared with the HIV-1 envelope protein, including the two broadly neutralizing monoclonal antibodies 2F5 and 4E10. Immunization of mice with a DNA vaccine expressing the HA/gp41 chimeric protein induced antibodies against the HIV gp41 protein and these antibodies exhibit neutralizing activity against infection by an HIV SF162 pseudovirus. These results demonstrate that the construction of such chimeric proteins can provide enhanced exposure of conserved epitopes in the HIV Env gp41 and may represent a novel vaccine design strategy for inducing broadly neutralizing antibodies against HIV

  14. Immune Reconstitution Kinetics following Intentionally Induced Mixed Chimerism by Nonmyeloablative Transplantation.

    Nayoun Kim

    Full Text Available Establishing mixed chimerism is a promising approach for inducing donor-specific transplant tolerance. The establishment and maintenance of mixed chimerism may enable long-term engraftment of organ transplants while minimizing the use of immunosuppressants. Several protocols for inducing mixed chimerism have been reported; however, the exact mechanism underlying the development of immune tolerance remains to be elucidated. Therefore, understanding the kinetics of engraftment during early post-transplant period may provide insight into establishing long-term mixed chimerism and permanent transplant tolerance. In this study, we intentionally induced allogeneic mixed chimerism using a nonmyeloablative regimen by host natural killer (NK cell depletion and T cell-depleted bone marrow (BM grafts in a major histocompatibility complex (MHC-mismatched murine model and analyzed the kinetics of donor (C57BL/6 and recipient (BALB/c engraftment in the weeks following transplantation. Donor BM cells were well engrafted and stabilized without graft-versus-host disease (GVHD as early as one week post-bone marrow transplantation (BMT. Donor-derived thymic T cells were reconstituted four weeks after BMT; however, the emergence of newly developed T cells was more obvious at the periphery as early as two weeks after BMT. Also, the emergence and changes in ratio of recipient- and donor-derived NKT cells and antigen presenting cells (APCs including dendritic cells (DCs and B cells were noted after BMT. Here, we report a longitudinal analysis of the development of donor- and recipient-originated hematopoietic cells in various lymphatic tissues of intentionally induced mixed chimerism mouse model during early post-transplant period. Through the understanding of immune reconstitution at early time points after nonmyeloablative BMT, we suggest guidelines on intentionally inducing durable mixed chimerism.

  15. A pumilio homolog in Polycelis sp.

    Yuwen, Yanqing; Dong, Zimei; Si, Xiaohui; Chen, Guangwen


    Pumilio proteins (PUMs), members of the pumilio/fem-3 mRNA-binding factor (PUF) family, are eukaryote-specific RNA-binding proteins. We isolated a 2,048-basepair cDNA fragment of a pumilio homolog from the planarian flatworm Polycelis sp. This pumilio protein (PyPUM) contains a conserved pumilio homology domain (PUM-HD) consisting of eight repeats and two flanking half repeats. PyPUM shows high similarity to Dugesia japonica pumilio (DjPUM) from another planarian D. japonica, and their PUM-HD also shows high similarity to each other. Furthermore, our data showed that there is a flatworm-specific spacer between repeats 7 and 8. Phylogenetic analysis showed that PyPUM has a closer relationship to other PUM homologs from flatworms. These results provide a foundation for future functional studies of pumilio gene in Polycelis sp. PMID:24292205

  16. Homological stability for oriented configuration spaces

    Palmer, Martin


    We prove homological stability for sequences of "oriented configuration spaces" as the number of points in the configuration goes to infinity. These are spaces of configurations of n points in a connected manifold M of dimension at least 2 which 'admits a boundary', with labels in a path-connected space X, and with an orientation: an ordering of the points up to even permutations. They are double covers of the corresponding unordered configuration spaces, where the points do not have this orientation. To prove our result we adapt methods from a paper of Randal-Williams, which proves homological stability in the unordered case. Interestingly the oriented configuration spaces stabilise more slowly than the unordered ones: the stability slope we obtain is one-third, compared to one-half in the unordered case (these are the best possible slopes in their respective cases). This result can also be interpreted as homological stability for unordered configuration spaces with certain twisted coefficients.

  17. Irradiated homologous costal cartilage for augmentation rhinoplasty

    Although the ideal reconstructive material for augmentation rhinoplasty continues to challenge plastic surgeons, there exists no report in the literature that confines the use of irradiated homologous costal cartilage, first reported by Dingman and Grabb in 1961, to dorsal nasal augmentation. The purpose of this paper is to present a retrospective analysis of the author's experience using irradiated homologous costal cartilage in augmentation rhinoplasty. Twenty-seven dorsal nasal augmentations were performed in 24 patients between 16 and 49 years of age with a follow-up ranging from 1 to 27 months. Good-to-excellent results were achieved in 83.3% (20 of 24). Poor results requiring revision were found in 16.7% (4 of 24). Complication rates included 7.4% infection (2 of 27) and 14.8% warping (4 of 27). The resorption rate was zero. These results compare favorably with other forms of nasal augmentation. Advantages and disadvantages of irradiated homologous costal cartilage are discussed

  18. Flare build-up study: Homologous flares group - Interim report

    Woodgate, B. E.


    When homologous flares are broadly defined as having footpoint structures in common, it is found that a majority of flares fall into homologous sets. Filament eruptions and mass ejection in members of an homologous flare set show that maintainance of the magnetic structure is not a necessary condition for homology.

  19. Homological and homotopical Dehn functions are different

    Abrams, Aaron; Dani, Pallavi; Young, Robert


    The homological and homotopical Dehn functions are different ways of measuring the difficulty of filling a closed curve inside a group or a space. The homological Dehn function measures fillings of cycles by chains, while the homotopical Dehn function measures fillings of curves by disks. Since the two definitions involve different sorts of boundaries and fillings, there is no a priori relationship between the two functions, but prior to this work there were no known examples of finitely-presented groups for which the two functions differ. This paper gives the first such examples, constructed by amalgamating a free-by-cyclic group with several Bestvina-Brady groups.

  20. Relative K-homology and normal operators

    Manuilov, Vladimir; Thomsen, Klaus


    -term exact sequence which generalizes the excision six-term exact sequence in the first variable of KK-theory. Subsequently we investigate the relative K-homology which arises from the group of relative extensions by specializing to abelian $C^*$-algebras. It turns out that this relative K-homology carries...... substantial information also in the operator theoretic setting from which the BDF theory was developed and we conclude the paper by extracting some of this information on approximation of normal operators....

  1. Sutured Floer homology distinguishes between Seifert surfaces

    Altman, Irida


    In this note we exhibit the first example of a knot in the three-sphere with a pair of minimal genus Seifert surfaces that can be distinguished using the sutured Floer homology of their complementary manifolds together with the Spin^c-grading. This answers a question of Juh\\'asz. More precisely, we show that the Euler characteristic of the sutured Floer homology of the complementary manifolds distinguishes between the two surfaces, and we exhibit an infinite family of knots with pairs of Seifert surfaces that can be distinguished in such a way.

  2. Sheaves on Graphs and Their Homological Invariants

    Friedman, Joel


    We introduce a notion of a sheaf of vector spaces on a graph, and develop the foundations of homology theories for such sheaves. One sheaf invariant, its "maximum excess," has a number of remarkable properties. It has a simple definition, with no reference to homology theory, that resembles graph expansion. Yet it is a "limit" of Betti numbers, and hence has a short/long exact sequence theory and resembles the $L^2$ Betti numbers of Atiyah. Also, the maximum excess is defined via a supermodul...

  3. New mesogenic homologous series of -methylcinnamates

    R A Vora; A K Prajapati


    Compounds of a new smectogenic homologous series of -methylcinnamates were prepared by condensing different 4--alkoxybenzoyl chloride with methoxyethyl trans-4-hydroxy- -methylcinnamate. In this series, the first six members are non-mesogenic. -Heptyloxy derivative exhibits monotropic smectic A phase whereas rest of the members exhibit enantiotropic smectic A mesophase. The compounds are characterized by combination of elemental analysis and spectroscopic techniques. Enthalpies of few homologues are measured by DSC techniques. Fluorescent properties are also observed. The thermal stabilities of the present series are compared with those of other structurally related mesogenic homologous series.

  4. Relative Derived Equivalences and Relative Homological Dimensions

    Sheng Yong PAN


    Let A be a small abelian category. For a closed subbifunctor F of Ext1A (−,−), Buan has generalized the construction of Verdier’s quotient category to get a relative derived category, where he localized with respect to F-acyclic complexes. In this paper, the homological properties of relative derived categories are discussed, and the relation with derived categories is given. For Artin algebras, using relative derived categories, we give a relative version on derived equivalences induced by F-tilting complexes. We discuss the relationships between relative homological dimensions and relative derived equivalences.

  5. Homology and cohomology of Rees semigroup algebras

    Grønbæk, Niels; Gourdeau, Frédéric; White, Michael C.


    Let S by a Rees semigroup, and let 1¹(S) be its convolution semigroup algebra. Using Morita equivalence we show that bounded Hochschild homology and cohomology of l¹(S) is isomorphic to those of the underlying discrete group algebra.......Let S by a Rees semigroup, and let 1¹(S) be its convolution semigroup algebra. Using Morita equivalence we show that bounded Hochschild homology and cohomology of l¹(S) is isomorphic to those of the underlying discrete group algebra....

  6. Contact homology of good toric contact manifolds

    Abreu, Miguel


    In this paper we show that any good toric contact manifold has well defined cylindrical contact homology and describe how it can be combinatorially computed from the associated moment cone. As an application we compute the cylindrical contact homology of a particularly nice family of examples that appear in the work of Gauntlett-Martelli-Sparks-Waldram on Sasaki-Einstein metrics. We show in particular that these give rise to a new infinite family of non-equivalent contact structures on $S^2 \\times S^{3}$ in the unique homotopy class of almost contact structures with vanishing first Chern class.

  7. Betti numbers and stability for configuration spaces via factorization homology

    Knudsen, Ben


    Using factorization homology, we realize the rational homology of the unordered configuration spaces of an arbitrary manifold $M$, possibly with boundary, as the homology of a Lie algebra constructed from the compactly supported cohomology of $M$. By locating the homology of each configuration space within the Chevalley-Eilenberg complex of this Lie algebra, we extend theorems of B\\"{o}digheimer-Cohen-Taylor and F\\'{e}lix-Thomas and give a new, combinatorial proof of the homological stability...

  8. Endosymbiotic gene transfer from prokaryotic pangenomes: Inherited chimerism in eukaryotes.

    Ku, Chuan; Nelson-Sathi, Shijulal; Roettger, Mayo; Garg, Sriram; Hazkani-Covo, Einat; Martin, William F


    Endosymbiotic theory in eukaryotic-cell evolution rests upon a foundation of three cornerstone partners--the plastid (a cyanobacterium), the mitochondrion (a proteobacterium), and its host (an archaeon)--and carries a corollary that, over time, the majority of genes once present in the organelle genomes were relinquished to the chromosomes of the host (endosymbiotic gene transfer). However, notwithstanding eukaryote-specific gene inventions, single-gene phylogenies have never traced eukaryotic genes to three single prokaryotic sources, an issue that hinges crucially upon factors influencing phylogenetic inference. In the age of genomes, single-gene trees, once used to test the predictions of endosymbiotic theory, now spawn new theories that stand to eventually replace endosymbiotic theory with descriptive, gene tree-based variants featuring supernumerary symbionts: prokaryotic partners distinct from the cornerstone trio and whose existence is inferred solely from single-gene trees. We reason that the endosymbiotic ancestors of mitochondria and chloroplasts brought into the eukaryotic--and plant and algal--lineage a genome-sized sample of genes from the proteobacterial and cyanobacterial pangenomes of their respective day and that, even if molecular phylogeny were artifact-free, sampling prokaryotic pangenomes through endosymbiotic gene transfer would lead to inherited chimerism. Recombination in prokaryotes (transduction, conjugation, transformation) differs from recombination in eukaryotes (sex). Prokaryotic recombination leads to pangenomes, and eukaryotic recombination leads to vertical inheritance. Viewed from the perspective of endosymbiotic theory, the critical transition at the eukaryote origin that allowed escape from Muller's ratchet--the origin of eukaryotic recombination, or sex--might have required surprisingly little evolutionary innovation. PMID:25733873

  9. Chimeric mouse-human IgG1 antibody that can mediate lysis of cancer cells

    A chimeric mouse-human antibody has been created that recognizes an antigen found on the surface of cells from many carcinomas. Immunoglobulin constant (C) domains of the mouse monoclonal antibody L6, C/sub γ2a/ and C/sub kappa/, were substituted by the human C/sub γ1/ and C/sub kappa/ by recombining cDNA modules encoding variable or C domains. The cDNA constructs were transfected into lymphoid cells for antibody production. The chimeric antibody and mouse L6 antibody bound to carcinoma cells with equal affinity and mediated complement-dependent cytolysis. In the presence of human effector cells, the chimeric antibody gave antibody-dependent cellular cytotoxicity at 100 times lower concentration than that needed for the mouse L6 antibody. The assay for lysis was carried out with 51Cr-labeled target calls. The chimeric antibody, but not the mouse L6 antibody, is effective against a melanoma line expressing small amounts of the L6 antigen. The findings point to the usefulness of the chimeric antibody approach for obtaining agents with strong antitumor activity for possible therapeutic use in man

  10. Recognition of base pair inversions in duplex by chimeric (alpha,beta) triplex-forming oligonucleotides.

    Timofeev, Edward N; Goryaeva, Baira V; Florentiev, Vladimir L


    DNA recognition by triplex-forming oligonucleotides (TFOs) is usually limited by homopurine-homopyrimidine sequence in duplexes. Modifications of the third strand may overcome this limitation. Chimeric alpha-beta TFOs are expected to form triplex DNA upon binding to non-regular sequence duplexes. In the present study we describe binding properties of chimeric alpha-beta oligodeoxynucleotides in the respect to short DNA duplexes with one, three, and five base pair inversions. Non-natural chimeric TFO's contained alpha-thymidine residues inside (GT) or (GA) core sequences. Modified residues were addressed to AT/TA inversions in duplexes. It was found in the non-denaturing gel-electrophoresis experiments that single or five adjacent base pair inversions in duplexes may be recognized by chimeric alpha-beta TFO's at 10 degrees C and pH 7.8. Three dispersed base pair inversions in the double stranded DNA prevented triplex formation by either (GT) or (GA) chimeras. Estimation of thermal stability of chimeric alpha-beta triplexes showed decrease in T(m) values as compared with unmodified complexes. PMID:16928141

  11. Generation and evaluation of a chimeric classical swine fever virus expressing a visible marker gene.

    Li, Yongfeng; Wang, Xiao; Sun, Yuan; Li, Lian-Feng; Zhang, Lingkai; Li, Su; Luo, Yuzi; Qiu, Hua-Ji


    Classical swine fever virus (CSFV) is a noncytopathogenic virus, and the incorporation of an enhanced green fluorescent protein (EGFP) tag into the viral genome provides a means of direct monitoring of viral infection without immunostaining. It is well established that the 3' untranslated region (3'-UTR) of the CSFV plays an important role in viral RNA replication. Although CSFV carrying a reporter gene and chimeric CSFV have been generated and evaluated, a chimeric CSFV with a visible marker has not yet been reported. Here, we generated and evaluated a chimeric virus containing the EGFP tag and the 3'-UTR from vaccine strain HCLV (C-strain) in the genetic background of the highly virulent CSFV Shimen strain. The chimeric marker CSFV was fluorescent and had an approximately 100-fold lower viral titer, lower replication level of viral genome, and weaker fluorescence intensity than the recombinant CSFV with only the EGFP tag or the parental virus. Furthermore, the marker chimera was avirulent and displayed no viremia in inoculated pigs, which were completely protected from lethal CSFV challenge as early as 15 days post-inoculation. The chimeric marker virus was visible in vitro and attenuated in vitro and in vivo, which suggests that CSFV can be engineered to produce attenuated variants with a visible marker to facilitate in vitro studies of CSFV infection and replication and to develop of novel vaccines against CSF. PMID:26614259

  12. Chimeric spider silk proteins mediated by intein result in artificial hybrid silks.

    Lin, Senzhu; Chen, Gefei; Liu, Xiangqin; Meng, Qing


    Hybrid silks hold a great potential as specific biomaterials due to its controlled mechanical properties. To produce fibers with tunable properties, here we firstly made chimeric proteins in vitro, called W2C4CT and W2C8CT, with ligation of MaSp repetitive modules (C) with AcSp modules (W) by intein trans splicing technology from smaller precursors without final yield reduction. Intein mediated chimeric proteins form fibers at a low concentration of 0.4 mg/mL in 50 mM K3 PO4 pH 7.5 just drawn by hand. Hybrid fibers show smoother surface, and also have stronger chemical resistance as compared with fibers from W2CT (W fibers) and mixture of W2CT/C8CT (MHF8 fibers). Fibers from chimeric protein W2C4CT (HFH4) have improved mechanical properties than W fibers; however, with more C modules W2C8CT fibers (HFH8) properties decreased, indicates the length proportion of various modules is very important and should be optimized for fibers with specific properties. Generally, hybrid silks generated via chimeric proteins, which can be simplified by intein trans splicing, has greater potential to produce fibers with tunable properties. Our research shows that intein mediated directional protein ligation is a novel way to make large chimeric spider silk proteins and hybrid silks. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 385-392, 2016. PMID:26948769

  13. Homological Perturbation Theory and Mirror Symmetry

    Jian ZHOU


    We explain how deformation theories of geometric objects such as complex structures,Poisson structures and holomorphic bundle structures lead to differential Gerstenhaber or Poisson al-gebras. We use homological perturbation theory to construct A∞ algebra structures on the cohomology,and their canonically defined deformations. Such constructions are used to formulate a version of A∞algebraic mirror symmetry.

  14. Cell biology of homologous recombination in yeast

    Eckert-Boulet, Nadine Valerie; Rothstein, Rodney; Lisby, Michael


    Homologous recombination is an important pathway for error-free repair of DNA lesions, such as single- and double-strand breaks, and for rescue of collapsed replication forks. Here, we describe protocols for live cell imaging of single-lesion recombination events in the yeast Saccharomyces...

  15. Planar open books and Floer homology

    Ozsvath, Peter; Stipsicz, Andras I.; Szabo, Zoltan


    Giroux has described a correspondence between open book decompositions on a 3--manifold and contact structures. In this paper we use Heegaard Floer homology to give restrictions on contact structures which correspond to open book decompositions with planar pages, generalizing a recent result of Etnyre.

  16. Homological aperiodic tilings of 3-dimensional geometries

    Nowak, Piotr W


    We construct the first aperiodic tiles for two amenable 3-dimensional Lie groups: Sol and the Heisenberg group. Our construction relies on the use of higher-dimensional uniformly finite homology. In particular, we settle completely the existence of aperiodic tiles for all of the non-compact geometries of 3-manifolds appearing in the geometrization conjecture.

  17. (Co)homology of Spectral Categories

    Campbell, Jonathan A.


    In this article we develop the cotangent complex and (co)homology theories for spectral categories. Along the way, we reproduce standard model structures on spectral categories. As applications, we show that the invariants to descend to stable $\\infty$-categories and we prove a stabilization result for spectral categories.

  18. Einstein Metrics on Rational Homology Spheres

    Boyer, Charles P.; Galicki, Krzysztof


    We prove the existence of Sasakian-Einstein metrics on infinitely many rational homology spheres in all odd dimensions greater than 3. In dimension 5 we obain somewhat sharper results. There are examples where the number of effective parameters in the Einstein metric grows exponentially with dimension.

  19. Homological stability for unordered configuration spaces

    Randal-Williams, Oscar


    This paper consists of two related parts. In the first part we give a self-contained proof of homological stability for the spaces C_n(M;X) of configurations of n unordered points in a connected open manifold M with labels in a path-connected space X, with the best possible integral stability range of 2* \\leq n. Along the way we give a new proof of the high connectivity of the complex of injective words. If the manifold has dimension at least three, we show that in rational homology the stability range may be improved to * \\leq n. In the second part we study to what extent the homology of the spaces C_n(M) can be considered stable when M is a closed manifold. In this case there are no stabilisation maps, but one may still ask if the dimensions of the homology groups over some field stabilise with n. We prove that this is true when M is odd-dimensional, or when the field is F_2 or Q. It is known to be false in the remaining cases.

  20. Homological stability for configuration spaces of manifolds

    Church, Thomas


    Let C_n(M) be the configuration space of n distinct ordered points in M. We prove that if M is any connected orientable manifold (closed or open), the homology groups H_i(C_n(M); Q) are representation stable in the sense of [Church-Farb]. Applying this to the trivial representation, we obtain as a corollary that the unordered configuration space B_n(M) satisfies classical homological stability: for each i, H_i(B_n(M); Q) is isomorphic to H_i(B_{n+1}(M); Q) for n > i. This improves on results of McDuff, Segal, and others for open manifolds. Applied to closed manifolds, this provides natural examples where rational homological stability holds even though integral homological stability fails. To prove the main theorem, we introduce the notion of monotonicity for a sequence of S_n--representations, which is of independent interest. Sequences that are both monotone and uniformly representation stable form an abelian category. Monotonicity provides a new mechanism for proving representation stability using spectral...

  1. Khovanov-Rozansky homology and Directed Cycles

    Wu, Hao


    We determine the cycle packing number of a directed graph using elementary projective algebraic geometry. Our idea is rooted in the Khovanov-Rozansky theory. In fact, using the Khovanov-Rozansky homology of a graph, we also obtain algebraic methods of detecting directed and undirected cycles containing a particular vertex or edge.

  2. The homology systole of hyperbolic Riemann surfaces

    Parlier, Hugo


    The main goal of this note is to show that the study of closed hyperbolic surfaces with maximum length systole is in fact the study of surfaces with maximum length homological systole. The same result is shown to be true for once-punctured surfaces, and is shown to fail for surfaces with a large number of cusps.

  3. Parametric representation of centrifugal pump homologous curves

    Veloso, Marcelo A.; Mattos, Joao R.L. de, E-mail:, E-mail: [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)


    Essential for any mathematical model designed to simulate flow transient events caused by pump operations is the pump performance data. The performance of a centrifugal pump is characterized by four basic quantities: the rotational speed, the volumetric flow rate, the dynamic head, and the hydraulic torque. The curves showing the relationships between these four variables are called the pump characteristic curves. The characteristic curves are empirically developed by the pump manufacturer and uniquely describe head and torque as functions of volumetric flow rate and rotation speed. Because of comprising a large amount of points, this configuration is not suitable for computational purposes. However, it can be converted to a simpler form by the development of the homologous curves, in which dynamic head and hydraulic torque ratios are expressed as functions of volumetric flow and rotation speed ratios. The numerical use of the complete set of homologous curves requires specification of sixteen partial curves, being eight for the dynamic head and eight for the hydraulic torque. As a consequence, the handling of homologous curves is still somewhat complicated. In solving flow transient problems that require the pump characteristic data for all the operation zones, the parametric form appears as the simplest way to deal with the homologous curves. In this approach, the complete characteristics of a pump can be described by only two closed curves, one for the dynamic head and other for the hydraulic torque, both in function of a single angular coordinate defined adequately in terms of the quotient between volumetric flow ratio and rotation speed ratio. The usefulness and advantages of this alternative method are demonstrated through a practical example in which the homologous curves for a pump of the type used in the main coolant loops of a pressurized water reactor (PWR) are transformed to the parametric form. (author)

  4. Targeted transcriptional repression using a chimeric TALE-SRDX repressor protein

    Mahfouz, Magdy M.


    Transcriptional activator-like effectors (TALEs) are proteins secreted by Xanthomonas bacteria when they infect plants. TALEs contain a modular DNA binding domain that can be easily engineered to bind any sequence of interest, and have been used to provide user-selected DNA-binding modules to generate chimeric nucleases and transcriptional activators in mammalian cells and plants. Here we report the use of TALEs to generate chimeric sequence-specific transcriptional repressors. The dHax3 TALE was used as a scaffold to provide a DNA-binding module fused to the EAR-repression domain (SRDX) to generate a chimeric repressor that targets the RD29A promoter. The dHax3. SRDX protein efficiently repressed the transcription of the RD29A

  5. The determination of lymphoid cell chimerism using peripheral blood lymphocytes from murine bone marrow chimeras

    A simple, rapid and accurate method was devised for determining lymphoid cell chimerism in bone marrow-reconstituted mice. Chimeras were produced by reconstituting lethally irradiated mice with semi-allogeneic bone marrow cells. Lymphocytes from the peripheral blood of individual chimeric mice were purified by sedimentation in dextran solution and differential flotation in Ficoll-Hypaque gradients. From 250-500 μl of blood, 1-7 x 105 cells were routinely obtained. The extent of chimerism was determined serologically by using peripheral blood lymphocytes as target cells in a dye exclusion microcytotoxicity assay. Using this new technique, approximately 80% of the reconstituted mice were found to be repopulated with lymphocytes of the donor type. (Auth.)

  6. Chimerism a natural ability to tolerate kin, evolutionary traits connecting mammalian and protochordates

    A Voskoboynik


    Full Text Available In the middle of the 20th century, Owen (1945, 1954 and Billingham et al. (1953 immunological studies suggested that fetal exposure to foreign antigens during pregnancy induce immunologic tolerance in the fetus. Recently, Mold et al. found that a substantial number of maternal cells crosses the placenta to reside in fetal lymph nodes and induces the development of regulatory T cells (Tregs that suppress fetal anti-maternal immunity. These Tregs cells persist till, at least, early adulthood. This result demonstrates how chimerism induces fetal tolerance to maternal antigens during mammalian pregnancy. Natural chimerism is the coexistence of two or more genomic lineages within the same individual. It is a common phenomenon which can be detected in a wide variety of multi-cellular organisms. In mammals, natural chimerism can be established during pregnancy between the mother and the fetus or between fetuses in a multiple embryos pregnancy. Restriction of natural chimerism mainly to kin is also observed in colonial marine protochordates. In protochordates, like Botryllus schlosseri, natural chimerism can be established through fusion of vasculature, between a parent colony and its progeny or between siblings (adult distinct colonies.The ability to tolerate a partial allogeneic individual and to create a chimeric entity between these colonies is determined by a single, highly polymorphic, fusion/histocompatibility locus (Fu/HC. Colonies that share at least one allele in their Fu/HC locus would fuse upon contact. A pair that does not share any Fu/HC allele would not. In the chimera, cells transmigrate between partners and in some cases, replace the germline and/or the somatic tissues of the host. This genotype replacement is mediated by stem cells (termed somatic/germ cell parasitism. Botryllus colonies propagate asexually through budding, therefore somatic stem cell parasitism in host colonies can induce the development of a partial allogeneic entity

  7. Interspecies chimeric complementation for the generation of functional human tissues and organs in large animal hosts.

    Wu, Jun; Izpisua Belmonte, Juan Carlos


    The past decade's rapid progress in human pluripotent stem cell (hPSC) research has generated hope for meeting the rising demand of organ donation, which remains the only effective cure for end-stage organ failure, a major cause of death worldwide. Despite the potential, generation of transplantable organs from hPSCs using in vitro differentiation is far-fetched. An in vivo interspecies chimeric complementation strategy relying on chimeric-competent hPSCs and zygote genome editing provides an auspicious alternative for providing unlimited organ source for transplantation. PMID:26820411

  8. Molecular chimerization of Pasteurella haemolytica leukotoxin to interleukin-2: effects on cytokine and antigen function.

    Hughes, H P; Campos, M.; Potter, A A; Babiuk, L. A.


    A chimeric recombinant protein composed of the lktA gene product from Pasteurella haemolytica fused to bovine interleukin-2 (IL-2) was made. The LKT-IL-2 chimera was compared with recombinant bovine IL-2 with regard to the ability to induce proliferative responses and LAK cell activity in bovine peripheral blood mononuclear cells in vitro. In both instances, chimerization had no effect on IL-2 activity. Similarly, the LKT component was unaffected in its ability to induce an effective immune r...

  9. Dosimetry of chimeric TNT in lung cancer patients

    Objective: To assess the irradiated absorptive dose of tumor and main critical organs chimeric tumor necrotic treatment (chTNT). Methods: In 9 lung cancer patients a single intravenous dose of 131I-chTNT (29.6±3.7) MBq/kg was administered. Blood samples were drawn at different time intervals and urine was collected for up to one week. Tissue distribution was followed for up to one week by gamma camera imaging. The geometric mean of the anterior and posterior counts was obtained from selected regions of interest (ROIs) to determine activity within the critical organs after being subtracted the background activity. Counts from thyroid were obtained from anterior images only. A background region was drawn below the thyroid gland to subtract underlying activity in the neck blood vessels. The geometric mean of the counts in the whole body scintigram at 0.5 h after injection was corrected for radioactive decay from the time of injection , this value being taken as 100%ID. The residence times for each critical organ and the remainder of the body were computed by dividing the area under their %ID/h curves by the 100%ID value. Absorbed doses to the whole body and to normal organ were computed from the residence time according to the MIRD scheme using Mirdose-3 software. Absorbed doses to tumor tissues were estimated using the same approach taken for normal organs. S-factors for tumors were estimated by comparison with normal organs of similar mass and position in the body. Results: Mean serum disappearance half time values for 131I-chTNT were α (4.9 ± 9.4) h, β (61.7 ± 21.2) h; and whole body, (99 ± 10) h. Mean urine biological clearance half time values was (90 ± 10) h. The absorbed dose of tumor was (8.28 ± 2.65) Gy, the tumor-to-nontumor ratio was 3.95 ± 1.55, while the absorbed dose of marrow was 0.44-0.73 Gy, thyroid was 0.47-23.09 Gy, ovaries was 0.50-0.77 Gy, testicles was 0.38-0.58 Gy, kidneys was 1.71- 4.55 Gy, liver was 1.18-2.63 Gy, and lungs was 1

  10. Homological algebra in strongly non-Abelian settings

    Grandis, Marco


    We propose here a study of 'semiexact' and 'homological' categories as a basis for a generalised homological algebra. Our aim is to extend the homological notions to deeply non-abelian situations, where satellites and spectral sequences can still be studied.This is a sequel of a book on 'Homological Algebra, The interplay of homology with distributive lattices and orthodox semigroups', published by the same Editor, but can be read independently of the latter.The previous book develops homological algebra in p-exact categories, i.e. exact categories in the sense of Puppe and Mitchell - a modera

  11. Chimeric Plant Calcium/Calmodulin-Dependent Protein Kinase Gene with a Neural Visinin-Like Calcium-Binding Domain

    Patil, Shameekumar; Takezawa, D.; Poovaiah, B. W.


    Calcium, a universal second messenger, regulates diverse cellular processes in eukaryotes. Ca-2(+) and Ca-2(+)/calmodulin-regulated protein phosphorylation play a pivotal role in amplifying and diversifying the action of Ca-2(+)- mediated signals. A chimeric Ca-2(+)/calmodulin-dependent protein kinase (CCaMK) gene with a visinin-like Ca-2(+)- binding domain was cloned and characterized from lily. The cDNA clone contains an open reading frame coding for a protein of 520 amino acids. The predicted structure of CCaMK contains a catalytic domain followed by two regulatory domains, a calmodulin-binding domain and a visinin-like Ca-2(+)-binding domain. The amino-terminal region of CCaMK contains all 11 conserved subdomains characteristic of serine/threonine protein kinases. The calmodulin-binding region of CCaMK has high homology (79%) to alpha subunit of mammalian Ca-2(+)/calmodulin-dependent protein kinase. The calmodulin-binding region is fused to a neural visinin-like domain that contains three Ca-2(+)-binding EF-hand motifs and a biotin-binding site. The Escherichia coli-expressed protein (approx. 56 kDa) binds calmodulin in a Ca-2(+)-dependent manner. Furthermore, Ca-45-binding assays revealed that CCaMK directly binds Ca-2(+). The CCaMK gene is preferentially expressed in developing anthers. Southern blot analysis revealed that CCaMK is encoded by a single gene. The structural features of the gene suggest that it has multiple regulatory controls and could play a unique role in Ca-2(+) signaling in plants.

  12. Homological Pisot Substitutions and Exact Regularity

    Barge, Marcy; Jones, Leslie; Sadun, Lorenzo


    We consider one-dimensional substitution tiling spaces where the dilatation (stretching factor) is a degree d Pisot number, and where the first rational Cech cohomology is d-dimensional. We construct examples of such "homological Pisot" substitutions that do not have pure discrete spectra. These examples are not unimodular, and we conjecture that the coincidence rank must always divide a power of the norm of the dilatation. To support this conjecture, we show that homological Pisot substitutions exhibit an Exact Regularity Property (ERP), in which the number of occurrences of a patch for a return length is governed strictly by the length. The ERP puts strong constraints on the measure of any cylinder set in the corresponding tiling space.

  13. Homological mirror symmetry and tropical geometry

    Catanese, Fabrizio; Kontsevich, Maxim; Pantev, Tony; Soibelman, Yan; Zharkov, Ilia


    The relationship between Tropical Geometry and Mirror Symmetry goes back to the work of Kontsevich and Y. Soibelman (2000), who applied methods of non-archimedean geometry (in particular, tropical curves) to Homological Mirror Symmetry. In combination with the subsequent work of Mikhalkin on the “tropical” approach to Gromov-Witten theory, and the work of Gross and Siebert, Tropical Geometry has now become a powerful tool. Homological Mirror Symmetry is the area of mathematics concentrated around several categorical equivalences connecting symplectic and holomorphic (or algebraic) geometry. The central ideas first appeared in the work of Maxim Kontsevich (1993). Roughly speaking, the subject can be approached in two ways: either one uses Lagrangian torus fibrations of Calabi-Yau manifolds (the so-called Strominger-Yau-Zaslow picture, further developed by Kontsevich and Soibelman) or one uses Lefschetz fibrations of symplectic manifolds (suggested by Kontsevich and further developed by Seidel). Tropical Ge...

  14. Homologous Pairing between Long DNA Double Helices

    Mazur, Alexey K.


    Molecular recognition between two double stranded (ds) DNA with homologous sequences may not seem compatible with the B-DNA structure because the sequence information is hidden when it is used for joining the two strands. Nevertheless, it has to be invoked to account for various biological data. Using quantum chemistry, molecular mechanics, and hints from recent genetics experiments, I show here that direct recognition between homologous dsDNA is possible through the formation of short quadruplexes due to direct complementary hydrogen bonding of major-groove surfaces in parallel alignment. The constraints imposed by the predicted structures of the recognition units determine the mechanism of complexation between long dsDNA. This mechanism and concomitant predictions agree with the available experimental data and shed light upon the sequence effects and the possible involvement of topoisomerase II in the recognition.

  15. Homological stability for unordered configuration spaces

    Randal-Williams, Oscar


    This paper consists of two related parts. In the first part we give a self-contained proof of homological stability for the spaces C_n(M;X) of configurations of n unordered points in a connected open manifold M with labels in a path-connected space X, with the best possible integral stability range...... of the spaces C_n(M) can be considered stable when M is a closed manifold. In this case there are no stabilisation maps, but one may still ask if the dimensions of the homology groups over some field stabilise with n. We prove that this is true when M is odd-dimensional, or when the field is F_2 or Q...

  16. Hochschild homology, lax codescent, and duplicial structure

    Garner, Richard; Lack, Stephen; Slevin, Paul


    We study the duplicial objects of Dwyer and Kan, which generalize the cyclic objects of Connes. We describe duplicial objects in terms of the decalage comonads, and we give a conceptual account of the construction of duplicial objects due to Bohm and Stefan. This is done in terms of a 2-categorical generalization of Hochschild homology. We also study duplicial structure on nerves of categories, bicategories, and monoidal categories.

  17. Nash equilibria via duality and homological selection

    Arnab Basu; Samik Basu; Mahan MJ


    Given a multifunction from to the -fold symmetric product Sym$_{k}(X)$, we use the Dold–Thom theorem to establish a homological selection theorem. This is used to establish existence of Nash equilibria. Cost functions in problems concerning the existence of Nash equilibria are traditionally multilinear in the mixed strategies. The main aim of this paper is to relax the hypothesis of multilinearity. We use basic intersection theory, Poincaré duality in addition to the Dold–Thom theorem.

  18. Recombineering Homologous Recombination Constructs in Drosophila

    Carreira-Rosario, Arnaldo; Scoggin, Shane; Shalaby, Nevine A.; Williams, Nathan David; Hiesinger, P. Robin; Buszczak, Michael


    The continued development of techniques for fast, large-scale manipulation of endogenous gene loci will broaden the use of Drosophila melanogaster as a genetic model organism for human-disease related research. Recent years have seen technical advancements like homologous recombination and recombineering. However, generating unequivocal null mutations or tagging endogenous proteins remains a substantial effort for most genes. Here, we describe and demonstrate techniques for using recombineeri...

  19. On the definition of homological critical value

    Govc, Dejan


    We point out that there is a problem with the definition of homological critical value (as defined in the widely cited paper \\cite{stability} by Cohen-Steiner, Edelsbrunner and Harer). Under that definition, the critical value lemma of \\cite{stability} in fact fails. We provide several counterexamples and a definition (due to Bubenik and Scott \\cite{categorification}) we feel should be preferred and under which the critical value lemma does indeed hold. One of the counterexamples we have foun...

  20. Persistent Homology and Partial Similarity of Shapes

    Di Fabio, Barbara; Landi, Claudia


    The ability to perform shape retrieval based not only on full similarity, but also partial similarity is a key property for any content-based search engine. We prove that persistence diagrams can reveal a partial similarity between two shapes by showing a common subset of points. This can be explained using the Mayer-Vietoris formulas that we develop for ordinary, relative and extended persistent homology. An experiment outlines the potential of persistence diagrams as shape descriptors in re...

  1. Irradiated homologous costal cartilage for augmentation rhinoplasty

    Lefkovits, G. (Lenox Hill Hospital, New York, NY (USA))


    Although the ideal reconstructive material for augmentation rhinoplasty continues to challenge plastic surgeons, there exists no report in the literature that confines the use of irradiated homologous costal cartilage, first reported by Dingman and Grabb in 1961, to dorsal nasal augmentation. The purpose of this paper is to present a retrospective analysis of the author's experience using irradiated homologous costal cartilage in augmentation rhinoplasty. Twenty-seven dorsal nasal augmentations were performed in 24 patients between 16 and 49 years of age with a follow-up ranging from 1 to 27 months. Good-to-excellent results were achieved in 83.3% (20 of 24). Poor results requiring revision were found in 16.7% (4 of 24). Complication rates included 7.4% infection (2 of 27) and 14.8% warping (4 of 27). The resorption rate was zero. These results compare favorably with other forms of nasal augmentation. Advantages and disadvantages of irradiated homologous costal cartilage are discussed.

  2. Note on homological modeling of the electric circuits

    Based on a simple example, it is explained how the homological analysis may be used for modeling of the electric circuits. The homological branch, mesh and nodal analyses are presented. Geometrical interpretations are given.

  3. Computing Small 1-Homological Models for Commutative Differential Graded Algebras

    Alvarez, Victor; Armario, Jose Andres; Frau, Maria Dolores; Gonzalez-Diaz, Rocio; Jimenez, Maria Jose; Real, Pedro; Silva, Beatriz


    We use homological perturbation machinery specific for the algebra category [P. Real. Homological Perturbation Theory and Associativity. Homology, Homotopy and Applications vol. 2, n. 5 (2000) 51-88] to give an algorithm for computing the differential structure of a small 1--homological model for commutative differential graded algebras (briefly, CDGAs). The complexity of the procedure is studied and a computer package in Mathematica is described for determining such models.

  4. Tocopherol and tocotrienol homologs in parenteral lipid emulsions

    Xu, Zhidong; Harvey, Kevin A.; Pavlina, Thomas M; Zaloga, Gary P.; Siddiqui, Rafat A.


    Parenteral lipid emulsions, which are made of oils from plant and fish sources, contain different types of tocopherols and tocotrienols (vitamin E homologs). The amount and types of vitamin E homologs in various lipid emulsions vary considerably and are not completely known. The objective of this analysis was to develop a quantitative method to determine levels of all vitamin E homologs in various lipid emulsions. An HPLC system was used to measure vitamin E homologs using a Pinnacle DB Silic...

  5. Equivariant geometric K-homology for compact Lie group actions

    Baum, Paul; Schick, Thomas


    Let G be a compact Lie-group, X a compact G-CW-complex. We define equivariant geometric K-homology groups K^G_*(X), using an obvious equivariant version of the (M,E,f)-picture of Baum-Douglas for K-homology. We define explicit natural transformations to and from equivariant K-homology defined via KK-theory (the "official" equivariant K-homology groups) and show that these are isomorphism.

  6. Thermostability of multidomain proteins: chimeric mesophilic/thermophilic elongation factors EF-Tu

    Šanderová, Hana; Maloň, Petr; Hůlková, Marta; Jonák, Jiří

    Varšava : FEBS, 2004, s. 7. [FEBS Forum for Young Scientists. Varšava (PL), 24.06.2004-26.06.2004] R&D Projects: GA ČR GA303/02/0689 Institutional research plan: CEZ:AV0Z5052915 Keywords : thermostability * EF-Tu * chimeric protein Subject RIV: EB - Genetics ; Molecular Biology

  7. Thermostability of multidomain proteins: chimeric mesophilic/thermophilic elongation factors EF-Tu

    Šanderová, Hana; Maloň, Petr; Hůlková, Marta; Jonák, Jiří

    Oxford : Blackwell Publishing, 2004, s. 219. [Meeting of the Federation of the European Biochemical Societies /29./. Varšava (PL), 26.06.2004-01.07.2004] R&D Projects: GA ČR GA303/02/0689 Institutional research plan: CEZ:AV0Z5052915 Keywords : thermostability * EF-Tu * chimeric protein Subject RIV: EB - Genetics ; Molecular Biology

  8. Preparation and Characterization of a Novel Chimeric Protein VEGI-CTT in Escherichia coli

    Jiping Cai


    Full Text Available Vascular endothelial cell growth inhibitor (VEGI is a recently identified antiangiogenic cytokine that belongs to the TNF superfamily, and could effectively inhibit endothelial cell proliferation and angiogenesis. Synthetic peptide CTT (CTTHWGFTLC has been found to suppress invasion and migration of both tumor and endothelial cells by potent and selective inhibition of MMP-2 and MMP-9. To prepare chimeric protein VEGI-CTT for more potent antitumor therapy, the recombinant expression vector pET-VEGI-CTT was constructed. This fusion protein was expressed in inclusion bodies in E. coli BL21 (DE3, and was refolded and purified by immobilized metal affinity chromatography using His-tag. Purified VEGI-CTT protein was characterized by proliferation assays of the endothelial cells and casein degradation assay in vitro. The results demonstrated that chimeric protein VEGI-CTT had a potent activity of antiangiogenesis through inhibiting the proliferation of endothelial cells, and could effectively reduce the activity of MMP-2 and MMP-9. The preliminarily in vivo study demonstrated that chimeric protein VEGI-CTT had more potent antitumor activity than VEGI and/or CTT peptide against CA46 human lymphoma xenografts in nude mice. Thus, these facts that are derived from the present study suggest that the chimeric protein VEGI-CTT may be used for tumor therapy in the future.

  9. Trypanosoma cruzi Differentiates and Multiplies within Chimeric Parasitophorous Vacuoles in Macrophages Coinfected with Leishmania amazonensis.

    Pessoa, Carina Carraro; Ferreira, Éden Ramalho; Bayer-Santos, Ethel; Rabinovitch, Michel; Mortara, Renato Arruda; Real, Fernando


    The trypanosomatids Leishmania amazonensis and Trypanosoma cruzi are excellent models for the study of the cell biology of intracellular protozoan infections. After their uptake by mammalian cells, the parasitic protozoan flagellates L. amazonensis and T. cruzi lodge within acidified parasitophorous vacuoles (PVs). However, whereas L. amazonensis develops in spacious, phagolysosome-like PVs that may enclose numerous parasites, T. cruzi is transiently hosted within smaller vacuoles from which it soon escapes to the host cell cytosol. To investigate if parasite-specific vacuoles are required for the survival and differentiation of T. cruzi, we constructed chimeric vacuoles by infection of L. amazonensis amastigote-infected macrophages with T. cruzi epimastigotes (EPIs) or metacyclic trypomastigotes (MTs). These chimeric vacuoles, easily observed by microscopy, allowed the entry and fate of T. cruzi in L. amazonensis PVs to be dynamically recorded by multidimensional imaging of coinfected cells. We found that although T. cruzi EPIs remained motile and conserved their morphology in chimeric vacuoles, T. cruzi MTs differentiated into amastigote-like forms capable of multiplying. These results demonstrate that the large adaptive vacuoles of L. amazonensis are permissive to T. cruzi survival and differentiation and that noninfective EPIs are spared from destruction within the chimeric PVs. We conclude that T. cruzi differentiation can take place in Leishmania-containing vacuoles, suggesting this occurs prior to their escape into the host cell cytosol. PMID:26975994

  10. Evidence for transcript networks composed of chimeric RNAs in human cells.

    Djebali, Sarah; Lagarde, Julien; Kapranov, Philipp; Lacroix, Vincent; Borel, Christelle; Mudge, Jonathan M; Howald, Cédric; Foissac, Sylvain; Ucla, Catherine; Chrast, Jacqueline; Ribeca, Paolo; Martin, David; Murray, Ryan R; Yang, Xinping; Ghamsari, Lila; Lin, Chenwei; Bell, Ian; Dumais, Erica; Drenkow, Jorg; Tress, Michael L; Gelpí, Josep Lluís; Orozco, Modesto; Valencia, Alfonso; van Berkum, Nynke L; Lajoie, Bryan R; Vidal, Marc; Stamatoyannopoulos, John; Batut, Philippe; Dobin, Alex; Harrow, Jennifer; Hubbard, Tim; Dekker, Job; Frankish, Adam; Salehi-Ashtiani, Kourosh; Reymond, Alexandre; Antonarakis, Stylianos E; Guigó, Roderic; Gingeras, Thomas R


    The classic organization of a gene structure has followed the Jacob and Monod bacterial gene model proposed more than 50 years ago. Since then, empirical determinations of the complexity of the transcriptomes found in yeast to human has blurred the definition and physical boundaries of genes. Using multiple analysis approaches we have characterized individual gene boundaries mapping on human chromosomes 21 and 22. Analyses of the locations of the 5' and 3' transcriptional termini of 492 protein coding genes revealed that for 85% of these genes the boundaries extend beyond the current annotated termini, most often connecting with exons of transcripts from other well annotated genes. The biological and evolutionary importance of these chimeric transcripts is underscored by (1) the non-random interconnections of genes involved, (2) the greater phylogenetic depth of the genes involved in many chimeric interactions, (3) the coordination of the expression of connected genes and (4) the close in vivo and three dimensional proximity of the genomic regions being transcribed and contributing to parts of the chimeric RNAs. The non-random nature of the connection of the genes involved suggest that chimeric transcripts should not be studied in isolation, but together, as an RNA network. PMID:22238572

  11. Viral Engineering of Chimeric Antigen Receptor Expression on Murine and Human T Lymphocytes.

    Hammill, Joanne A; Afsahi, Arya; Bramson, Jonathan L; Helsen, Christopher W


    The adoptive transfer of a bolus of tumor-specific T lymphocytes into cancer patients is a promising therapeutic strategy. In one approach, tumor specificity is conferred upon T cells via engineering expression of exogenous receptors, such as chimeric antigen receptors (CARs). Here, we describe the generation and production of both murine and human CAR-engineered T lymphocytes using retroviruses. PMID:27581020

  12. Custom-engineered chimeric foot-and-mouth disease vaccine elicits protective immune responses in pigs

    Chimeric foot-and-mouth disease viruses (FMDV) of which the antigenic properties can be readily manipulated is a potentially powerful approach in the control of foot-and-mouth disease (FMD) in sub-Saharan Africa. FMD vaccine application is complicated by the extensive variability of the South Africa...

  13. In Silico Design of a Chimeric Protein Containing Antigenic Fragments of Helicobacter pylori; A Bioinformatic Approach

    Mohammad, Nazanin; Karsabet, Mehrnaz Taghipour; Amani, Jafar; Ardjmand, Abolfazl; Zadeh, Mohsen Razavi; Gholi, Mohammad Khalifeh; Saffari, Mahmood; Ghasemi, Amir


    Helicobacter pylori is a global health problem which has encouraged scientists to find new ways to diagnose, immunize and eradicate the H. pylori infection. In silico studies are a promising approach to design new chimeric antigen having the immunogenic potential of several antigens. In order to obtain such benefit in H. pylori vaccine study, a chimeric gene containing four fragments of FliD sequence (1-600 bp), UreB (327-334 bp),VacA (744-805 bp) and CagL(51-100 bp) which have a high density of B- and T-cell epitopes was designed. The secondary and tertiary structures of the chimeric protein and other properties such as stability, solubility and antigenicity were analyzed. The in silico results showed that after optimizing for the purpose of expression in Escherichia coli BL21, the solubility and antigenicity of the construct fragments were highly retained. Most regions of the chimeric protein were found to have a high antigenic propensity and surface accessibility. These results would be useful in animal model application and accounted for the development of an epitope-based vaccine against the H. pylori. PMID:27335622

  14. Ligand-mediated negative regulation of a chimeric transmembrane receptor tyrosine phosphatase

    Desai, D M; Sap, J; Schlessinger, J;


    inactivate the EGFR-CD45 chimera in a manner that is dependent on dimerization of the chimeric protein. Inactivation of EGFR-CD45 chimera function results in the loss of TCR signaling, indicating that CD45 function is continuously required for TCR-mediated proximal signaling events. These results suggest...

  15. Alloreactive regulatory T cells allow the generation of mixed chimerism and transplant tolerance

    Paulina eRuiz


    Full Text Available The induction of donor-specific transplant tolerance is one of the main goals of modern immunology. Establishment of a mixed chimerism state in the transplant recipient has proven to be a suitable strategy for the induction of long-term allograft tolerance; however, current experimental recipient preconditioning protocols have many side effects, and are not feasible for use in future therapies. In order to improve the current mixed chimerism induction protocols, we developed a non-myeloablative bone-marrow transplant protocol using retinoic acid induced alloantigen-specific Tregs, clinically available immunosuppressive drugs and lower doses of irradiation. We demonstrate that retinoic acid induced alloantigen-specific Tregs in addition to a non-myeloablative bone-marrow transplant protocol generates stable mixed chimerism and induce tolerance to allogeneic secondary skin allografts in mice. Therefore, the establishment of mixed chimerism through the use of donor-specific Tregs rather than non-specific immunosuppression could have a potential use in organ transplantation.

  16. SAT Type Foot-and-Mouth Disease (FMD) Chimeric Vaccine Elicits Protection in Pigs

    The recent development of infectious cDNA clone technology for foot-and-mouth disease (FMD), Southern African Territories (SAT) viruses has provided a valuable tool for genetic and biological characterization of field and laboratory strains. Recombinant chimeric viruses, containing the capsid-coding...

  17. Origination of an X-linked testes chimeric gene by illegitimate recombination in Drosophila.


    Full Text Available The formation of chimeric gene structures provides important routes by which novel proteins and functions are introduced into genomes. Signatures of these events have been identified in organisms from wide phylogenic distributions. However, the ability to characterize the early phases of these evolutionary processes has been difficult due to the ancient age of the genes or to the limitations of strictly computational approaches. While examples involving retrotransposition exist, our understanding of chimeric genes originating via illegitimate recombination is limited to speculations based on ancient genes or transfection experiments. Here we report a case of a young chimeric gene that has originated by illegitimate recombination in Drosophila. This gene was created within the last 2-3 million years, prior to the speciation of Drosophila simulans, Drosophila sechellia, and Drosophila mauritiana. The duplication, which involved the Bällchen gene on Chromosome 3R, was partial, removing substantial 3' coding sequence. Subsequent to the duplication onto the X chromosome, intergenic sequence was recruited into the protein-coding region creating a chimeric peptide with approximately 33 new amino acid residues. In addition, a novel intron-containing 5' UTR and novel 3' UTR evolved. We further found that this new X-linked gene has evolved testes-specific expression. Following speciation of the D. simulans complex, this novel gene evolved lineage-specifically with evidence for positive selection acting along the D. simulans branch.


    Marek's disease virus, a herpes virus, and avian leucosis virus subgroup J, a retrovirus were used for experimental co-infection of chicks. Two consecutive trials were performed in attempt to evaluate the formation and persistence of chimeric molecules that would indicate retro-viral integration int...

  19. Duality and products in algebraic (co)homology theories

    Kowalzig, N.; Kraehmer, U.


    The origin and interplay of products and dualities in algebraic (co)homology theories is ascribed to a ×A-Hopf algebra structure on the relevant universal enveloping algebra. This provides a unified treatment for example of results by Van den Bergh about Hochschild (co)homology and by Huebschmann about Lie–Rinehart (co)homology.

  20. The rapid generation of chimerical genes expanding protein diversity in zebrafish

    Zou Ming


    Full Text Available Abstract Background Variation of gene number among species indicates that there is a general process of new gene origination. One of the major mechanism providing raw materials for the origin of new genes is gene duplication. Retroposition, as a special type of gene duplication- the RNA-based duplication, has been found to play an important role in new gene evolution in mammals and plants, but little is known about the process in the teleostei genome. Results Here we screened the zebrafish genome for identification of retrocopies and new chimerical retrogenes and investigated their origination and evolution. We identified 652 retrocopies, of which 440 are intact retrogenes and 212 are pseudogenes. Retrocopies have long been considered evolutionary dead ends without functional significance due to the presumption that retrocopies lack the regulatory element needed for expression. However, 437 transcribed retrocopies were identified from all of the retrocopies. This discovery combined with the substitution analysis suggested that the majority of all retrocopies are subject to negative selection, indicating that most of the retrocopies may be functional retrogenes. Moreover, we found that 95 chimerical retrogenes had recruited new sequences from neighboring genomic regions that formed de novo splice sites, thus generating new intron-containing chimeric genes. Based on our analysis of 38 pairs of orthologs between Cyprinus carpio and Danio rerio, we found that the synonymous substitution rate of zebrafish genes is 4.13×10-9 substitution per silent site per year. We also found 10 chimerical retrogenes that were created in the last 10 million years, which is 7.14 times the rate of 0.14 chimerical retrogenes per million years in the primate lineage toward human and 6.25 times the rate of 0.16 chimerical genes per million years in Drosophila. This is among the most rapid rates of generation of chimerical genes, just next to the rice. Conclusion There is

  1. Chimeric Peptides as Implant Functionalization Agents for Titanium Alloy Implants with Antimicrobial Properties

    Yucesoy, Deniz T.; Hnilova, Marketa; Boone, Kyle; Arnold, Paul M.; Snead, Malcolm L.; Tamerler, Candan


    Implant-associated infections can have severe effects on the longevity of implant devices and they also represent a major cause of implant failures. Treating these infections associated with implants by antibiotics is not always an effective strategy due to poor penetration rates of antibiotics into biofilms. Additionally, emerging antibiotic resistance poses serious concerns. There is an urge to develop effective antibacterial surfaces that prevent bacterial adhesion and proliferation. A novel class of bacterial therapeutic agents, known as antimicrobial peptides (AMPs), are receiving increasing attention as an unconventional option to treat septic infection, partly due to their capacity to stimulate innate immune responses and for the difficulty of microorganisms to develop resistance towards them. While host and bacterial cells compete in determining the ultimate fate of the implant, functionalization of implant surfaces with AMPs can shift the balance and prevent implant infections. In the present study, we developed a novel chimeric peptide to functionalize the implant material surface. The chimeric peptide simultaneously presents two functionalities, with one domain binding to a titanium alloy implant surface through a titanium-binding domain while the other domain displays an antimicrobial property. This approach gains strength through control over the bio-material interfaces, a property built upon molecular recognition and self-assembly through a titanium alloy binding domain in the chimeric peptide. The efficiency of chimeric peptide both in-solution and absorbed onto titanium alloy surface was evaluated in vitro against three common human host infectious bacteria, Streptococcus mutans, Staphylococcus epidermidis, and Escherichia coli. In biological interactions such as occur on implants, it is the surface and the interface that dictate the ultimate outcome. Controlling the implant surface by creating an interface composed chimeric peptides may therefore

  2. Murine immune responses to a Plasmodium vivax-derived chimeric recombinant protein expressed in Brassica napus

    Chung Nam-Jun


    Full Text Available Abstract Background To develop a plant-based vaccine against Plasmodium vivax, two P. vivax candidate proteins were chosen. First, the merozoite surface protein-1 (MSP-1, a major asexual blood stage antigen that is currently considered a strong vaccine candidate. Second, the circumsporozoite protein (CSP, a component of sporozoites that contains a B-cell epitope. Methods A synthetic chimeric recombinant 516 bp gene encoding containing PvMSP-1, a Pro-Gly linker motif, and PvCSP was synthesized; the gene, named MLC, encoded a total of 172 amino acids. The recombinant gene was modified with regard to codon usage to optimize gene expression in Brassica napus. The Ti plasmid inducible gene transfer system was used for MLC chimeric recombinant gene expression in B. napus. Gene expression was confirmed by polymerase chain reaction (PCR, beta-glucuronidase reporter gene (GUS assay, and Western blot. Results The MLC chimeric recombinant protein expressed in B. napus had a molecular weight of approximately 25 kDa. It exhibited a clinical sensitivity of 84.21% (n = 38 and a clinical specificity of 100% (n = 24 as assessed by enzyme-linked immunosorbent assay (ELISA. Oral immunization of BALB/c mice with MLC chimeric recombinant protein successfully induced antigen-specific IgG1 production. Additionally, the Th1-related cytokines IL-12 (p40, TNF, and IFN-γ were significantly increased in the spleens of the BALB/c mice. Conclusions The chimeric MLC recombinant protein produced in B. napus has potential as both as an antigen for diagnosis and as a valuable vaccine candidate for oral immunization against vivax malaria.

  3. Enhancement of mucosal immune responses by chimeric influenza HA/SHIV virus-like particles

    To enhance mucosal immune responses using simian/human immunodeficiency virus-like particles (SHIV VLPs), we have produced novel phenotypically mixed chimeric influenza HA/SHIV VLPs and used them to immunize C57BL/6J mice intranasally. Antibody and cytotoxic T-cell (CTL) responses as well as cytokine production in both systemic and mucosal sites were compared after immunization with SHIV VLPs or chimeric HA/SHIV VLPs. By using enzyme-linked immunosorbent assay (ELISA), the levels of serum IgG and mucosal IgA to the HIV envelope protein (Env) were found to be highest in the group immunized with chimeric HA/SHIV VLPs. Furthermore, the highest titer of serum neutralizing antibody against HIV Env was found with the group immunized with chimeric HA/SHIV VLPs. Analysis of the IgG1/IgG2a ratio indicated that a TH1-oriented immune response resulted from these VLP immunizations. HA/SHIV VLP-immunized mice also showed significantly higher CTL responses than those observed in SHIV VLP-immunized mice. Moreover, a MHC class I restricted T-cell activation ELISPOT assay showed a mixed type of TH1/TH2 cytokines in the HA/SHIV VLP-immunized mice, indicating that the chimeric VLPs can enhance both humoral and cellular immune responses to the HIV Env protein at multiple mucosal and systemic sites. The results indicate that incorporation of influenza HA into heterotypic VLPs may be highly effective for targeting vaccines to mucosal surfaces

  4. The expression and genetic immunization of chimeric fragment of Hantaan virus M and S segments

    Hemorrhagic fever with renal syndrome (HFRS), which is characterized by severe symptoms and high mortality, is caused by hantavirus. There are still no effective prophylactic vaccines directed to HFRS until now. In this research, we fused expressed G2 fragment of M segment and 0.7 kb fragment of S segment. We expect it could be a candidate vaccine. Chimeric gene G2S0.7 was first expressed in prokaryotic expression system pGEX-4T. After inducing expressed fusion proteins, GST-G2S0.7 was induced and its molecular weight was about 100 kDa. Meanwhile, the fusion protein kept the activity of its parental proteins. Further, BALB/c mice were vaccinated by the chimeric gene. ELISA, cell microculture neutralization test in vitro were used to detect the humoral immune response in immunized BALB/c mice. Lymphocyte proliferation assay was used to detect the cellular immune response. The results showed that the chimeric gene could simultaneously evoke specific antibody against nucleocapsid protein (NP) and glycoprotein (GP). And the immunized mice of every group elicited neutralizing antibodies with different titers. But the titers were low. Lymphocyte proliferation assay results showed that the stimulation indexes of splenocytes of chimeric gene to NP and GP were significantly higher than that of control. It suggested that the chimeric gene of Hantaan virus containing G2 fragment of M segment and 0.7 kb fragment of S segment could directly elicit specific anti-Hantaan virus humoral and cellular immune response in BALB/c mice

  5. Chimeric SV40 virus-like particles induce specific cytotoxicity and protective immunity against influenza A virus without the need of adjuvants

    Virus-like particles (VLPs) are a promising vaccine platform due to the safety and efficiency. However, it is still unclear whether polyomavirus-based VLPs are useful for this purpose. Here, we attempted to evaluate the potential of polyomavirus VLPs for the antiviral vaccine using simian virus 40 (SV40). We constructed chimeric SV40-VLPs carrying an HLA-A⁎02:01-restricted, cytotoxic T lymphocyte (CTL) epitope derived from influenza A virus. HLA-A⁎02:01-transgenic mice were then immunized with the chimeric SV40-VLPs. The chimeric SV40-VLPs effectively induced influenza-specific CTLs and heterosubtypic protection against influenza A viruses without the need of adjuvants. Because DNase I treatment of the chimeric SV40-VLPs did not disrupt CTL induction, the intrinsic adjuvant property may not result from DNA contaminants in the VLP preparation. In addition, immunization with the chimeric SV40-VLPs generated long-lasting memory CTLs. We here propose that the chimeric SV40-VLPs harboring an epitope may be a promising CTL-based vaccine platform with self-adjuvant properties. - Highlights: • We constructed chimeric SV40-VLPs carrying an influenza virus-derived CTL epitope. • Chimeric SV40-VLPs induce influenza-specific CTLs in mice without adjuvants. • Chimeric SV40-VLPs induce heterosubtypic protection against influenza A viruses. • Chimeric SV40-VLPs induce long-lasting memory CTLs. • Chimeric SV40-VLPs is a promising vaccine platform with self-adjuvant properties

  6. Excluded volume effect enhances the homology pairing of model chromosomes

    Takamiya, Kazunori; Isami, Shuhei; Nishimori, Hiraku; Awazu, Akinori


    To investigate the structural dynamics of the homology pairing of polymers, we mod- eled the scenario of homologous chromosome pairings during meiosis in Schizosaccharomyces pombe, one of the simplest model organisms of eukaryotes. We consider a simple model consist- ing of pairs of homologous polymers with the same structures that are confined in a cylindrical container, which represents the local parts of chromosomes contained in an elongated nucleus of S. pombe. Brownian dynamics simulations of this model showed that the excluded volume effects among non-homological chromosomes and the transitional dynamics of nuclear shape serve to enhance the pairing of homologous chromosomes.

  7. Exponential growth of colored HOMFLY-PT homology

    Wedrich, Paul


    We define reduced colored sl(N) link homologies and use deformation spectral sequences to characterize their dependence on color and rank. We then define reduced colored HOMFLY-PT homologies and prove that they arise as large N limits of sl(N) homologies. Together, these results allow proofs of many aspects of the physically conjectured structure of the family of type A link homologies. In particular, we verify a conjecture of Gorsky, Gukov and Sto\\v{s}i\\'c about the growth of colored HOMFLY-PT homologies.

  8. A PHF8 homolog in C. elegans promotes DNA repair via homologous recombination.

    Changrim Lee

    Full Text Available PHF8 is a JmjC domain-containing histone demethylase, defects in which are associated with X-linked mental retardation. In this study, we examined the roles of two PHF8 homologs, JMJD-1.1 and JMJD-1.2, in the model organism C. elegans in response to DNA damage. A deletion mutation in either of the genes led to hypersensitivity to interstrand DNA crosslinks (ICLs, while only mutation of jmjd-1.1 resulted in hypersensitivity to double-strand DNA breaks (DSBs. In response to ICLs, JMJD-1.1 did not affect the focus formation of FCD-2, a homolog of FANCD2, a key protein in the Fanconi anemia pathway. However, the dynamic behavior of RPA-1 and RAD-51 was affected by the mutation: the accumulations of both proteins at ICLs appeared normal, but their subsequent disappearance was retarded, suggesting that later steps of homologous recombination were defective. Similar changes in the dynamic behavior of RPA-1 and RAD-51 were seen in response to DSBs, supporting a role of JMJD-1.1 in homologous recombination. Such a role was also supported by our finding that the hypersensitivity of jmjd-1.1 worms to ICLs was rescued by knockdown of lig-4, a homolog of Ligase 4 active in nonhomologous end-joining. The hypersensitivity of jmjd-1.1 worms to ICLs was increased by rad-54 knockdown, suggesting that JMJD-1.1 acts in parallel with RAD-54 in modulating chromatin structure. Indeed, the level of histone H3 Lys9 tri-methylation, a marker of heterochromatin, was higher in jmjd-1.1 cells than in wild-type cells. We conclude that the histone demethylase JMJD-1.1 influences homologous recombination either by relaxing heterochromatin structure or by indirectly regulating the expression of multiple genes affecting DNA repair.

  9. Hochschild homology and microlocal Euler classes

    Kashiwara, Masaki


    We define the notion of a Hochschild kernel on a manifold M. Roughly speaking, it is a sheaf on M x M for which the formalism of Hochschild homology applies. We associate a microlocal Euler class to such a kernel, a cohomology class with values in the relative dualizing complex of the cotangent bundle over M and we prove that this class is functorial with respect to the composition of kernels. This generalizes, unifies and simplifies various results of (relative) index theorems for constructible sheaves, D-modules and elliptic pairs.

  10. Periodic cyclic homology of affine Hecke algebras

    Solleveld, Maarten


    This is the author's PhD-thesis, which was written in 2006. The version posted here is identical to the printed one. Instead of an abstract, the short list of contents: Preface 5 1 Introduction 9 2 K-theory and cyclic type homology theories 13 3 Affine Hecke algebras 61 4 Reductive p-adic groups 103 5 Parameter deformations in affine Hecke algebras 129 6 Examples and calculations 169 A Crossed products 223 Bibliography 227 Index 237 Samenvatting 245 Curriculum vitae 253

  11. L^2-homology for compact quantum groups

    Kyed, David


    A notion of L^2-homology for compact quantum groups is introduced, generalizing the classical notion for countable, discrete groups. If the compact quantum group in question has tracial Haar state, it is possible to define its L^2-Betti numbers and Novikov-Shubin invariants/capacities. It is proved that these L^2-Betti numbers vanish for the Gelfand dual of a compact Lie group and that the zeroth Novikov-Shubin invariant equals the dimension of the underlying Lie group. Finally, we relate our...

  12. Homology of lipoprotein lipase to pancreatic lipase.

    Ben-Avram, C M; Ben-Zeev, O; Lee, T.D. (Taunia D.); Haaga, K; Shively, J. E.; Goers, J; Pedersen, M.E; Reeve, J R; Schotz, M C


    Bovine milk lipoprotein lipase was subjected to amino acid sequence analysis. The first 19 amino-terminal residues were Asp-Arg-Ile-Thr-Gly-Gly-Lys-Asp-Phe-Arg-Asp-Ile-Glu-Ser-Lys-Phe-Ala-Leu- Arg. In addition, reversed-phase high-performance liquid chromatography of a tryptic digest of reduced and alkylated lipase resolved a number of peptides, five of which contained cysteine. Sequence analysis of the tryptic peptides revealed in most instances a close homology to porcine pancreatic lipase....

  13. Hochschild Homology and Cohomology of Klein Surfaces

    Frédéric Butin


    Full Text Available Within the framework of deformation quantization, a first step towards the study of star-products is the calculation of Hochschild cohomology. The aim of this article is precisely to determine the Hochschild homology and cohomology in two cases of algebraic varieties. On the one hand, we consider singular curves of the plane; here we recover, in a different way, a result proved by Fronsdal and make it more precise. On the other hand, we are interested in Klein surfaces. The use of a complex suggested by Kontsevich and the help of Groebner bases allow us to solve the problem.

  14. Detailed assessment of homology detection using different substitution matrices

    LI Jing; WANG Wei


    Homology detection plays a key role in bioinformatics, whereas substitution matrix is one of the most important components in homology detection. Thus, besides the improvement of alignment algorithms, another effective way to enhance the accuracy of homology detection is to use proper substitution matrices or even construct new matrices.A study on the features of various matrices and on the comparison of the performances between different matrices in homology detection enable us to choose the most proper or optimal matrix for some specific applications. In this paper, by taking BLOSUM matrices as an example, some detailed features of matrices in homology detection are studied by calculating the distributions of numbers of recognized proteins over different sequence identities and sequence lengths. Our results clearly showed that different matrices have different preferences and abilities to the recognition of remote homologous proteins. Furthermore, detailed features of the various matrices can be used to improve the accuracy of homology detection.

  15. The Homology Groups of a Partial Trace Monoid Action

    Husainov, Ahmet A


    The aim of this paper is to investigate the homology groups of mathematical models of concurrency. We study the Baues-Wirsching homology groups of a small category associated with a partial monoid action on a set. We prove that these groups can be reduced to the Leech homology groups of the monoid. For a trace monoid with an action on a set, we will build a cubical complex of free Abelian groups with homology groups isomorphic to the integral homology groups of the action category. It allows us to solve the problem posed by the author in 2004 of the constructing an algorithm for computing homology groups of the CE nets. We describe the algorithm and give examples of calculating the homology groups.

  16. Transfers for ramified covering maps in homology and cohomology

    Marcelo A. Aguilar


    Full Text Available Making use of a modified version, due to McCord, of the Dold-Thom construction of ordinary homology, we give a simple topological definition of a transfer for ramified covering maps in homology with arbitrary coefficients. The transfer is induced by a suitable map between topological groups. We also define a new cohomology transfer which is dual to the homology transfer. This duality allows us to show that our homology transfer coincides with the one given by L. Smith. With our definition of the homology transfer we can give simpler proofs of the properties of the known transfer and of some new ones. Our transfers can also be defined in Karoubi's approach to homology and cohomology. Furthermore, we show that one can define mixed transfers from other homology or cohomology theories to the ordinary ones.

  17. A homological study of Green polynomials

    Kato, Syu


    We interpret the orthogonality relation of Kostka polynomials arising from complex reflection groups (c.f. [Shoji, Invent. Math. 74 (1983), J. Algebra 245 (2001)] and [Lusztig, Adv. Math. 61 (1986)]) in terms of homological algebra. This leads us to the notion of Kostka system, which can be seen as a categorical counter-part of Kostka polynomials. Then, we show that every generalized Springer correspondence (in good characteristic) (c.f. [Lusztig, Invent. Math. 75 (1984)]) gives rise to a Kostka system. This enables us to see the top-term generation property of the homology of generalized Springer fibers, and the transition formula of Kostka polynomials between two generalized Springer correspondences of type $\\mathsf{BC}$. The latter enhances one of the main results from [Ciubotaru-Kato-K, Invent. Math., to appear] to its graded version. In the appendix, we present a purely algebraic proof that a Kostka system exists for type $\\mathsf{A}$, and therefore one can skip geometric sections \\S 3--5 to see the key ...

  18. SANSparallel: interactive homology search against Uniprot.

    Somervuo, Panu; Holm, Liisa


    Proteins evolve by mutations and natural selection. The network of sequence similarities is a rich source for mining homologous relationships that inform on protein structure and function. There are many servers available to browse the network of homology relationships but one has to wait up to a minute for results. The SANSparallel webserver provides protein sequence database searches with immediate response and professional alignment visualization by third-party software. The output is a list, pairwise alignment or stacked alignment of sequence-similar proteins from Uniprot, UniRef90/50, Swissprot or Protein Data Bank. The stacked alignments are viewed in Jalview or as sequence logos. The database search uses the suffix array neighborhood search (SANS) method, which has been re-implemented as a client-server, improved and parallelized. The method is extremely fast and as sensitive as BLAST above 50% sequence identity. Benchmarks show that the method is highly competitive compared to previously published fast database search programs: UBLAST, DIAMOND, LAST, LAMBDA, RAPSEARCH2 and BLAT. The web server can be accessed interactively or programmatically at It can be used to make protein functional annotation pipelines more efficient, and it is useful in interactive exploration of the detailed evidence supporting the annotation of particular proteins of interest. PMID:25855811

  19. Sheaves on Graphs and Their Homological Invariants

    Friedman, Joel


    We introduce a notion of a sheaf of vector spaces on a graph, and develop the foundations of homology theories for such sheaves. One sheaf invariant, its "maximum excess," has a number of remarkable properties. It has a simple definition, with no reference to homology theory, that resembles graph expansion. Yet it is a "limit" of Betti numbers, and hence has a short/long exact sequence theory and resembles the $L^2$ Betti numbers of Atiyah. Also, the maximum excess is defined via a supermodular function, which gives the maximum excess much stronger properties than one has of a typical Betti number. The maximum excess gives a simple interpretation of an important graph invariant, which will be used to study the Hanna Neumann Conjecture in a future paper. Our sheaf theory can be viewed as a vast generalization of algebraic graph theory: each sheaf has invariants associated to it---such as Betti numbers and Laplacian matrices---that generalize those in classical graph theory.

  20. Dosimetry of chimeric TNT in lung cancer patients

    Objective: A mouse-human chimeric Tumor-Necrosis-Therapy (chTNT) monoclonal antibody is directed against single-stranded DNA a universal nuclear antigen accessible in the necrotic cell within most solid tumors, which has potential for the radioimmunotherapy of many solid tumors. The radiation dosimetry of the 131I-chTNT was evaluated in 9 lung cancer patients (age 18-74 years, mean weight (49.6±6.5) kg). Methods: A single intravenous dose of (29.6±3.7) MBq/kg was administered. Blood samples were drawn at different time intervals and urine was collected for up to one week. Tissue distribution was followed for up to one week by gamma camera imaging. The geometric mean of the counts in the whole body scintigram at 0.5 h after infusion was corrected for radioactivity decay from the time of infusion, this value being taken as 100%ID. The geometric mean of the anterior and posterior counts was obtained from selected region of interested (ROI) to determine activity within the critical organs after being subtracted the background activity. Counts from thyroid were obtained from anterior images only. A background region was drawn below the thyroid gland to subtract underlying activity in the neck blood vessels. The residence times for brain, lungs, liver, spleen, kidneys, heart, thyroid and the whole body were computed by dividing the area under their %ID/h curves by the 100%ID value. Before integration, the activity-time curves were fitted to an algebraic function with an exponential tail (r>0.90). The absorbed doses were computed from the residence time according to the Medical Internal Radiation Dose (MIRD) scheme using MIRDOSE 3.0 software. The adult female and male phantoms were selected. The MIRDOSE 3.0 dynamic bladder model was used to calculate residence times for urinary bladder content assuming a urinary elimination fraction of 1.0 with a bladder-voiding interval of 4h. Absorbed doses to tumor tissues were estimated using the same approach taken for normal

  1. The assay of thyrotropin receptor antibodies with human TSH/LH-CG chimeric receptor expressed on chinese hamster ovary cells

    TSH/LH-CG chimera cDNA is transfected to CHO-K1 cell to obtain the chimeric receptor expressed on the cell surface. The optimal conditions for TSAb and TSBAb measurements are determined using chimeric receptors and under these conditions activity of TSAb and TSBAb in the sera of the Graves' patients. The results obtained are compared to those of TSAb assays using FRTL5 cells CHO-TSHR cells which have wild type human TSH receptor. The transfection procedure of chimeric receptor gene to CHO-K1 cells are on going. The optimal conditions for TSAb and TSBAb measurement using chimeric receptor will be determined after success of transfection procedure. If this study is successfully completed, not only the heterogeneity of Graves. IgG but also pathogenesis of Graves' disease will be elucidated. (author). 25 refs

  2. The assay of thyrotropin receptor antibodies with human TSH/LH-CG chimeric receptor expressed on chinese hamster ovary cells

    Yi, Ka Hee; Kim, Chang Min [Korea Cancer Center Hospital, Seoul (Korea, Republic of)


    TSH/LH-CG chimera cDNA is transfected to CHO-K1 cell to obtain the chimeric receptor expressed on the cell surface. The optimal conditions for TSAb and TSBAb measurements are determined using chimeric receptors and under these conditions activity of TSAb and TSBAb in the sera of the Graves` patients. The results obtained are compared to those of TSAb assays using FRTL5 cells CHO-TSHR cells which have wild type human TSH receptor. The transfection procedure of chimeric receptor gene to CHO-K1 cells are on going. The optimal conditions for TSAb and TSBAb measurement using chimeric receptor will be determined after success of transfection procedure. If this study is successfully completed, not only the heterogeneity of Graves. IgG but also pathogenesis of Graves` disease will be elucidated. (author). 25 refs.

  3. Transfection of beta-casein chimeric gene and hormonal induction of its expression in primary murine mammary epithelial cells.

    Yoshimura, M.; Oka, T


    To study the regulatory sequence elements responsible for casein gene expression, we constructed a chimeric gene containing 5.3 kilobases (kb) of the 5'-flanking sequence and 1.6 kb of the 3'-flanking sequence of the mouse beta-casein gene fused to the bacterial chloramphenicol acetyl-transferase (CAT) gene. The chimeric gene was transfected by the calcium phosphate-precipitation procedure into primary mouse mammary epithelial cells prepared from pregnant mice. The transfection procedure had ...

  4. Chatter detection in turning using persistent homology

    Khasawneh, Firas A.; Munch, Elizabeth


    This paper describes a new approach for ascertaining the stability of stochastic dynamical systems in their parameter space by examining their time series using topological data analysis (TDA). We illustrate the approach using a nonlinear delayed model that describes the tool oscillations due to self-excited vibrations in turning. Each time series is generated using the Euler-Maruyama method and a corresponding point cloud is obtained using the Takens embedding. The point cloud can then be analyzed using a tool from TDA known as persistent homology. The results of this study show that the described approach can be used for analyzing datasets of delay dynamical systems generated both from numerical simulation and experimental data. The contributions of this paper include presenting for the first time a topological approach for investigating the stability of a class of nonlinear stochastic delay equations, and introducing a new application of TDA to machining processes.

  5. Towards Stratification Learning through Homology Inference

    Bendich, Paul; Wang, Bei


    A topological approach to stratification learning is developed for point cloud data drawn from a stratified space. Given such data, our objective is to infer which points belong to the same strata. First we define a multi-scale notion of a stratified space, giving a stratification for each radius level. We then use methods derived from kernel and cokernel persistent homology to cluster the data points into different strata, and we prove a result which guarantees the correctness of our clustering, given certain topological conditions; some geometric intuition for these topological conditions is also provided. Our correctness result is then given a probabilistic flavor: we give bounds on the minimum number of sample points required to infer, with probability, which points belong to the same strata. Finally, we give an explicit algorithm for the clustering, prove its correctness, and apply it to some simulated data.

  6. Suicide Gene Therapy to Increase the Safety of Chimeric Antigen Receptor-Redirected T Lymphocytes

    Monica Casucci, Attilio Bondanza


    Full Text Available Chimeric antigen receptors (CARs are generated by fusing the antigen-binding motif of a monoclonal antibody (mAb with the signal transduction machinery of the T-cell receptor (TCR. The genetic modification of T lymphocytes with chimeric receptors specific for tumor-associated antigens (TAAs allows for the redirection towards tumor cells. Clinical experience with CAR-redirected T cells suggests that antitumor efficacy associates with some degree of toxicity, especially when TAA expression is shared with healthy tissues. This situation closely resembles the case of allogeneic hematopoietic stem cell transplantation (HSCT, wherein allorecognition causes both the graft-versus-leukemia (GVL effect and graft-versus-host disease (GVHD. Suicide gene therapy, i.e. the genetic induction of a conditional suicide phenotype into donor T cells, enables dissociating the GVL effect from GVHD. Applying suicide gene modification to CAR-redirected T cells may therefore greatly increase their safety profile and facilitate their clinical development.

  7. Human glial chimeric mice reveal astrocytic dependence of JC virus infection

    Kondo, Yoichi; Windrem, Martha S; Zou, Lisa;


    with humanized white matter by engrafting human glial progenitor cells (GPCs) into neonatal immunodeficient and myelin-deficient mice. Intracerebral delivery of JCV resulted in infection and subsequent demyelination of these chimeric mice. Human GPCs and astrocytes were infected more readily than...... oligodendrocytes, and viral replication was noted primarily in human astrocytes and GPCs rather than oligodendrocytes, which instead expressed early viral T antigens and exhibited apoptotic death. Engraftment of human GPCs in normally myelinated and immunodeficient mice resulted in humanized white matter that was...... chimeric for human astrocytes and GPCs. JCV effectively propagated in these mice, which indicates that astroglial infection is sufficient for JCV spread. Sequencing revealed progressive mutation of the JCV capsid protein VP1 after infection, suggesting that PML may evolve with active infection. These...

  8. Very Long Term Stability of Mixed Chimerism after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Hematologic Malignancies

    Emmanuel Levrat


    Full Text Available The objective of this study is to analyze the evolution of chimerism of all patients transplanted for hematologic malignancies in our unit during a 20-year period, alive without relapse at 1 year after allogeneic hematopoietic stem cell transplantation (HSCT. Chimerism was tested using short tandem repeat polymorphisms after separation into mononuclear cells and granulocytes by Ficoll density gradient centrifugation. Of 155 patients studied, 89 had full chimerism (FC, 36 mononuclear cells mixed chimerism (MNC-MC, and 30 granulocytic MC with or without mononuclear cells MC (Gran-MC. Survival was significantly better in MNC-MC than in Gran-MC patients, with FC patients being intermediate. There was more disease relapse in the Gran-MC group but not in the MNC-MC group as compared to FC. MC was stable up to 21 years in the MNC-MC group and up to 19 years in the Gran-MC group. Of MC patients alive at 10 years, MC persisted in 83% in the MNC-MC and 57% in the Gran-MC groups. In conclusion, mixed chimerism may remain stable over a very long time period. In survivors without relapse at 1 year after HSCT, determining lineage specific chimerism may be useful as outcome differs, MNC-MC being associated with better outcome than Gran-MC.


    Solar flare emissions in the chromosphere often appear as elongated ribbons on both sides of the magnetic polarity inversion line (PIL), which has been regarded as evidence of a typical configuration of magnetic reconnection. However, flares having a circular ribbon have rarely been reported, although it is expected in the fan-spine magnetic topology involving reconnection at a three-dimensional (3D) coronal null point. We present five circular ribbon flares with associated surges, using high-resolution and high-cadence Hα blue wing observations obtained from the recently digitized films of Big Bear Solar Observatory. In all the events, a central parasitic magnetic field is encompassed by the opposite polarity, forming a circular PIL traced by filament material. Consequently, a flare kernel at the center is surrounded by a circular flare ribbon. The four homologous jet-related flares on 1991 March 17 and 18 are of particular interest, as (1) the circular ribbons brighten sequentially, with cospatial surges, rather than simultaneously, (2) the central flare kernels show an intriguing 'round-trip' motion and become elongated, and (3) remote brightenings occur at a region with the same magnetic polarity as the central parasitic field and are co-temporal with a separate phase of flare emissions. In another flare on 1991 February 25, the circular flare emission and surge activity occur successively, and the event could be associated with magnetic flux cancellation across the circular PIL. We discuss the implications of these observations combining circular flare ribbons, homologous jets, and remote brightenings for understanding the dynamics of 3D magnetic restructuring.

  10. A roadmap for the computation of persistent homology

    Otter, Nina; Tillmann, Ulrike; Grindrod, Peter; Harrington, Heather A


    Persistent homology is a method used in topological data analysis to study qualitative features of data, which is robust to perturbations, dimension independent and provides statistical summaries of the outputs. Despite recent progress, the computation of persistent homology for large data sets remains an open problem. We investigate the challenges of computing persistent homology and navigate through the different algorithms and data structures. Specifically, we evaluate the (currently available) open source implementations of persistent homology computations on a wide range of synthetic and real-world data sets, and indicate which algorithms and implementations are best suited to these data. We provide guidelines for the computation of persistent homology, make our own implementations used in this study available, and put forward measures to quantify the challenges of the computation of persistent homology.

  11. Skin Recurrence of Transformed Mycosis Fungoides Postumbilical Cord Blood Transplant despite Complete Donor Chimerism

    Rahul Pawar; Anup Kasi Loknath Kumar; Janet Woodroof; Wei Cui; Joseph McGuirk; Sunil Abhyankar; Sid Ganguly; Anurag Singh; Tara Lin; Omar Aljitawi


    Background. Allogeneic stem cell transplant is the treatment of choice for systemic cutaneous T-cell lymphoma (CTCL) which provides graft-versus-lymphoma effect. Herein we discuss a case of recurrence of CTCL skin lesions after cord blood transplant in a patient who continued to have 100% donor chimerism in bone marrow. Case Presentation. A 48-year-old female with history of mycosis fungoides (MF) presented with biopsy proven large cell transformation of MF. PET scan revealed multiple adenop...

  12. Bone marrow chimeric mice reveal a dual role for CD36 in Plasmodium berghei ANKA infection

    Febbraio Maria


    Full Text Available Abstract Background Adhesion of Plasmodium-infected red blood cells (iRBC to different host cells, ranging from endothelial to red blood cells, is associated to malaria pathology. In vitro studies have shown the relevance of CD36 for adhesion phenotypes of Plasmodium falciparum iRBC such as sequestration, platelet mediated clumping and non-opsonic uptake of iRBC. Different adhesion phenotypes involve different host cells and are associated with different pathological outcomes of disease. Studies with different human populations with CD36 polymorphisms failed to attribute a clear role to CD36 expression in human malaria. Up to the present, no in vivo model has been available to study the relevance of different CD36 adhesion phenotypes to the pathological course of Plasmodium infection. Methods Using CD36-deficient mice and their control littermates, CD36 bone marrow chimeric mice, expressing CD36 exclusively in haematopoietic cells or in non-haematopoietic cells, were generated. Irradiated CD36-/- and wild type mice were also reconstituted with syngeneic cells to control for the effects of irradiation. The reconstituted mice were infected with Plasmodium berghei ANKA and analysed for the development of blood parasitaemia and neurological symptoms. Results All mice reconstituted with syngeneic bone marrow cells as well as chimeric mice expressing CD36 exclusively in non-haematopoietic cells died from experimental cerebral malaria between day 6 and 12 after infection. A significant proportion of chimeric mice expressing CD36 only in haematopoietic cells did not die from cerebral malaria. Conclusion The analysis of bone marrow chimeric mice reveals a dual role of CD36 in P. berghei ANKA infection. Expression of CD36 in haematopoietic cells, most likely macrophages and dendritic cells, has a beneficial effect that is masked in normal mice by adverse effects of CD36 expression in non-haematopoietic cells, most likely endothelial cells.

  13. Chimeric viruses blur the borders between the major groups of eukaryotic single-stranded DNA viruses

    Roux, Simon; Enault, Francois; Bronner, Gisèle; Vaulot, Daniel; Forterre, Patrick; Krupovic, Mart


    Metagenomic studies have uncovered an astonishing diversity of ssDNA viruses encoding replication proteins (Reps) related to those of eukaryotic Circoviridae, Geminiviridae or Nanoviridae; however, exact evolutionary relationships among these viruses remain obscure. Recently, a unique chimeric virus (CHIV) genome, which has apparently emerged via recombination between ssRNA and ssDNA viruses, has been discovered. Here we report on the assembly of 13 new CHIV genomes recovered f...

  14. Chimerism in M1 plants of Vicia faba, Capsicum annuum and Linum usitatissimum

    One important task of our group at IAEA is to develop procedures aiming to improve sampling of M2 seeds to facilitate the recovery of a maximum number of induced mutations in crop plants. Results from studies on three species are reported in this paper. Seeds have been mutagen treated and the chimeric M1 plants were progeny tested in M2. The position of the M2 seeds on the M1 plants has been recorded

  15. Oxidative stress and the mechanical properties of naturally occurring chimeric collagen-containing fibers.

    Sun, C.; E. Vaccaro; Waite, J. H.


    The byssal threads of marine mussels are a fiber-reinforced composite material. Fibers are continuous, separated by matrix, and consist of chimeric collagens that encompass within the same primary protein structure domains corresponding to collagen, polyhistidine, and either elastin or dragline spider silk. The elastic modulus (stiffness) of the proximal portion of byssal threads was measured by cyclic stress-strain analysis at 50% extension. Before measurement, the threads were conditioned b...

  16. Chimeric nucleolin aptamer with survivin DNAzyme for cancer cell targeted delivery.

    Subramanian, Nithya; Kanwar, Jagat R; Akilandeswari, Balachandran; Kanwar, Rupinder K; Khetan, Vikas; Krishnakumar, Subramanian


    A chimeric aptamer-DNAzyme conjugate was generated for the first time using a nucleolin aptamer (NCL-APT) and survivin Dz (Sur_Dz) and exhibited the targeted killing of cancer cells. This proof of concept of using an aptamer for the delivery of DNAzyme can be applied to other cancer types to target survivin in cancer cells in a specific manner. PMID:25797393

  17. Chimeric External Control to Quantify Cell Free DNA in Plasma Samples by Real Time PCR

    Eini, Maryam; Behzad-Behbahani, Abbas; Takhshid, Mohammad Ali; Ramezani, Amin; Rafiei Dehbidi, Gholam Reza; Okhovat, Mohammad Ali; Farhadi, Ali; Alavi, Parniyan


    Background: DNA isolation procedure can significantly influence the quantification of DNA by real time PCR specially when cell free DNA (cfDNA) is the subject. To assess the extraction efficiency, linearity of the extraction yield, presence of co-purified inhibitors and to avoid problems with fragment size relevant to cfDNA, development of appropriate External DNA Control (EDC) is challenging. Using non-human chimeric nucleotide sequences, an EDC was developed for standardization of qPCR for ...

  18. T cells expressing VHH-directed oligoclonal chimeric HER2 antigen receptors

    Jamnani, Fatemeh Rahimi; Rahbarizadeh, Fatemeh; Shokrgozar, Mohammad Ali;


    Adoptive cell therapy with engineered T cells expressing chimeric antigen receptors (CARs) originated from antibodies is a promising strategy in cancer immunotherapy. Several unsuccessful trials, however, highlight the need for alternative conventional binding domains and the better combination of...... costimulatory endodomains for CAR construction to improve the effector functions of the engineered T cells. Camelid single-domain antibodies (VHHs), which are the smallest single domain antibodies, can endow great targeting ability to CAR-engineered T cells....

  19. Design and Development of Therapies using Chimeric Antigen Receptor-Expressing T cells

    Dotti, Gianpietro; Gottschalk, Stephen; Savoldo, Barbara; Brenner, Malcolm K


    Investigators developed chimeric antigen receptors (CARs) for expression on T cells more than 25 years ago. When the CAR is derived from an antibody, the resultant cell should combine the desirable targeting features of an antibody (e.g. lack of requirement for major histocompatibility complex recognition, ability to recognize non-protein antigens) with the persistence, trafficking and effector functions of a T-cell. This article describes how the past two decades have seen a crescendo of res...

  20. Domain exchange: characterization of a chimeric lipase of hepatic lipase and lipoprotein lipase.

    Wong, H; Davis, R. C.; Nikazy, J; Seebart, K E; Schotz, M C


    Hepatic lipase and lipoprotein lipase hydrolyze fatty acids from triacylglycerols and are critical in the metabolism of circulating lipoproteins. The two lipases are similar in size and amino acid sequence but are distinguished by functional differences in substrate preference and cofactor requirement. Presumably, these distinctions result from structural differences in functional domains. To begin localization of these domains, a chimeric lipase was constructed composed of the N-terminal 329...

  1. Remote control of therapeutic T cells through a small molecule-gated chimeric receptor

    Wu, Chia-Yung; Kole T Roybal; Puchner, Elias M.; Onuffer, James; Lim, Wendell A.


    There is growing promise in using engineered cells as therapeutic agents. For example, synthetic Chimeric Antigen Receptors (CARs) can redirect T cells to recognize and eliminate tumor cells expressing specific antigens. Despite promising clinical results, excessive activity and poor control over such engineered T cells can cause severe toxicities. We present the design of “ON-switch” CARs that enable small molecule-control over T cell therapeutic functions, while still retaining antigen spec...

  2. Identification of chimeric antigen receptors that mediate constitutive or inducible proliferation of T cells

    Frigault, Matthew J.; Lee, Jihyun; Basil, Maria Ciocca; Carpenito, Carmine; Motohashi, Shinichiro; Scholler, John; Kawalekar, Omkar U.; Guedan, Sonia; McGettigan, Shannon E; Posey, Avery D; Ang, Sonny; Cooper, Laurence J. N.; Platt, Jesse M.; Johnson, F. Brad; Paulos, Chrystal M.


    This study compared second generation chimeric antigen receptors encoding signaling domains composed of CD28, ICOS and 4-1BB. Here we report that certain CARs endow T cells with the ability to undergo long-term autonomous proliferation. Transduction of primary human T-cell with lentiviral vectors encoding some of the CARs resulted in sustained proliferation for up to three months following a single stimulation through the TCR. Sustained numeric expansion was independent of cognate antigen and...

  3. Topology of the RNA polymerase active center probed by chimeric rifampicin-nucleotide compounds.

    Mustaev, A; Zaychikov, E; Severinov, K.; Kashlev, M; Polyakov, A.; Nikiforov, V.; Goldfarb, A


    Spatial organization of the binding sites for the priming substrate, the template DNA, and the transcription inhibitor rifampicin (Rif) in Escherichia coli RNA polymerase (EC was probed with chimeric compounds in which Rif is covalently attached to a ribonucleotide. The compounds bind to RNA polymerase in bifunctional manner and serve as substrates for RNA chain extension, yielding chains up to 8 nucleotides in length, with Rif linked to their 5' termini. These products act as potent...

  4. Impact of homologous and non-homologous recombination in the genomic evolution of Escherichia coli

    Didelot Xavier


    Full Text Available Abstract Background Escherichia coli is an important species of bacteria that can live as a harmless inhabitant of the guts of many animals, as a pathogen causing life-threatening conditions or freely in the non-host environment. This diversity of lifestyles has made it a particular focus of interest for studies of genetic variation, mainly with the aim to understand how a commensal can become a deadly pathogen. Many whole genomes of E. coli have been fully sequenced in the past few years, which offer helpful data to help understand how this important species evolved. Results We compared 27 whole genomes encompassing four phylogroups of Escherichia coli (A, B1, B2 and E. From the core-genome we established the clonal relationships between the isolates as well as the role played by homologous recombination during their evolution from a common ancestor. We found strong evidence for sexual isolation between three lineages (A+B1, B2, E, which could be explained by the ecological structuring of E. coli and may represent on-going speciation. We identified three hotspots of homologous recombination, one of which had not been previously described and contains the aroC gene, involved in the essential shikimate metabolic pathway. We also described the role played by non-homologous recombination in the pan-genome, and showed that this process was highly heterogeneous. Our analyses revealed in particular that the genomes of three enterohaemorrhagic (EHEC strains within phylogroup B1 have converged from originally separate backgrounds as a result of both homologous and non-homologous recombination. Conclusions Recombination is an important force shaping the genomic evolution and diversification of E. coli, both by replacing fragments of genes with an homologous sequence and also by introducing new genes. In this study, several non-random patterns of these events were identified which correlated with important changes in the lifestyle of the bacteria, and

  5. Variants of equivariant Seiberg-Witten Floer homology

    Marcolli, M.; Wang, B-L


    For a rational homology 3-sphere Y with a Spin c structure s, we show that simple algebraic manipulations of our construction of equivariant Seiberg-Witten Floer homology in lead to a collection of variants, which are all topological invariants. We establish a long exact sequence relating them and we show that they satisfy a duality under orientation reversal. We explain their relation to the equivariant Seiberg-Witten Floer (co)homologies introduced in [loc. cit.]. We conjecture the equivale...

  6. A local homology theory for linearly compact modules

    We introduce a local homology theory for linearly modules which is in some sense dual to the local cohomology theory of A. Grothendieck. Some basic properties of local homology modules are shown such as: the vanishing and non-vanishing, the noetherianness of local homology modules. By using duality, we extend some well-known results in theory of local cohomology of A. Grothendieck. (author)

  7. Euler Integration of Gaussian Random Fields and Persistent Homology

    Bobrowski, Omer


    In this paper we extend the notion of the Euler characteristic to persistent homology and give the relationship between the Euler integral of a function and the Euler characteristic of the function's persistent homology. We then proceed to compute the expected Euler integral of a Gaussian random field using the Gaussian kinematic formula and obtain a simple closed form expression. This results in the first computation of a quantitative descriptor for the persistent homology of a Gaussian random field.

  8. Development of a high-throughput microfluidic integrated microarray for the detection of chimeric bioweapons.

    Sheppod, Timothy; Satterfield, Brent; Hukari, Kyle W.; West, Jason A. A.; Hux, Gary A.


    The advancement of DNA cloning has significantly augmented the potential threat of a focused bioweapon assault, such as a terrorist attack. With current DNA cloning techniques, toxin genes from the most dangerous (but environmentally labile) bacterial or viral organism can now be selected and inserted into robust organism to produce an infinite number of deadly chimeric bioweapons. In order to neutralize such a threat, accurate detection of the expressed toxin genes, rather than classification on strain or genealogical decent of these organisms, is critical. The development of a high-throughput microarray approach will enable the detection of unknowns chimeric bioweapons. The development of a high-throughput microarray approach will enable the detection of unknown bioweapons. We have developed a unique microfluidic approach to capture and concentrate these threat genes (mRNA's) upto a 30 fold concentration. These captured oligonucleotides can then be used to synthesize in situ oligonucleotide copies (cDNA probes) of the captured genes. An integrated microfluidic architecture will enable us to control flows of reagents, perform clean-up steps and finally elute nanoliter volumes of synthesized oligonucleotides probes. The integrated approach has enabled a process where chimeric or conventional bioweapons can rapidly be identified based on their toxic function, rather than being restricted to information that may not identify the critical nature of the threat.

  9. Human-animal chimeras: ethical issues about farming chimeric animals bearing human organs.

    Bourret, Rodolphe; Martinez, Eric; Vialla, François; Giquel, Chloé; Thonnat-Marin, Aurélie; De Vos, John


    Recent advances in stem cells and gene engineering have paved the way for the generation of interspecies chimeras, such as animals bearing an organ from another species. The production of a rat pancreas by a mouse has demonstrated the feasibility of this approach. The next step will be the generation of larger chimeric animals, such as pigs bearing human organs. Because of the dramatic organ shortage for transplantation, the medical needs for such a transgressive practice are indisputable. However, there are serious technical barriers and complex ethical issues that must be discussed and solved before producing human organs in animals. The main ethical issues are the risks of consciousness and of human features in the chimeric animal due to a too high contribution of human cells to the brain, in the first case, or for instance to limbs, in the second. Another critical point concerns the production of human gametes by such chimeric animals. These worst-case scenarios are obviously unacceptable and must be strictly monitored by careful risk assessment, and, if necessary, technically prevented. The public must be associated with this ethical debate. Scientists and physicians have a critical role in explaining the medical needs, the advantages and limits of this potential medical procedure, and the ethical boundaries that must not be trespassed. If these prerequisites are met, acceptance of such a new, borderline medical procedure may prevail, as happened before for in-vitro fertilization or preimplantation genetic diagnosis. PMID:27356872

  10. Skin Recurrence of Transformed Mycosis Fungoides Postumbilical Cord Blood Transplant despite Complete Donor Chimerism

    Rahul Pawar


    Full Text Available Background. Allogeneic stem cell transplant is the treatment of choice for systemic cutaneous T-cell lymphoma (CTCL which provides graft-versus-lymphoma effect. Herein we discuss a case of recurrence of CTCL skin lesions after cord blood transplant in a patient who continued to have 100% donor chimerism in bone marrow. Case Presentation. A 48-year-old female with history of mycosis fungoides (MF presented with biopsy proven large cell transformation of MF. PET scan revealed multiple adenopathy in abdomen and chest suspicious for lymphoma and skin biopsy showed large cell transformation. She was treated with multiple cycles of chemotherapy. Posttherapy PET scan showed resolution of lymphadenopathy. Later she underwent ablative preparative regimen followed by single cord blood transplant. Bone marrow chimerism studies at day +60 after transplant showed 100% donor cells without presence of lymphoma. However 5 months after transplant she had recurrence of MF with the same genotype as prior skin lesion. Bone marrow chimerism study continued to show 100% donor cells. Conclusion. A differential graft-versus-lymphoma effect in our case prevented lymphoma recurrence systemically but failed to do so in skin. We hypothesize that this response may be due to presence of other factors in the bone marrow and lymph node microenvironments preventing recurrence in these sites.