Binds

Distribution by Scientific Domains
Distribution within Chemistry

Kinds of Binds

  • antibody bind
  • complex bind
  • covalently bind
  • double bind
  • factor bind
  • family bind
  • inhibitor bind
  • molecule bind
  • peptide bind
  • protein bind
  • subunit bind


  • Selected Abstracts


    BOOK REVIEW DIALOGUE: TIES THAT BIND

    AMERICAN BUSINESS LAW JOURNAL, Issue 3 2000
    (Thomas Donaldson, 306 pages), Harvard Business School, Thomas W. Dunfee
    First page of article [source]


    THE BINDS THAT TIE: CIVILITY AND SOCIAL DIFFERENCE

    EDUCATIONAL THEORY, Issue 2 2002
    Cris Mayo
    First page of article [source]


    DNA Aptamers that Bind to PQQGDH as an Electrochemical Labeling Tool

    ELECTROANALYSIS, Issue 11 2009
    Yuko Osawa
    Abstract We screened DNA aptamers that bind to pyrroquinoline quinone glucose dehydrogenase (PQQGDH) for the development of an electrochemical labeling tool. PQQGDH is an excellent enzyme for the signal amplification of biosensors. We focused on DNA aptamers as labeling agents and tried to select those DNA aptamers that bind to PQQGDH without affecting its enzymatic activity. After 7 rounds of screening, one aptamer was obtained: ,PGa4'. It bound to PQQGDH with specificity and showed no effect on the glucose dehydrogenase (GDH) activity. Moreover, beads labeled with PQQGDH via PGa4 generated an electrical current upon glucose addition. Therefore, we believe that the PGa4 aptamer against PQQGDH may become a powerful labeling tool for electrochemical biosensors. [source]


    The Ties That Bind: Infanticide, Gender, and Society

    HISTORY COMPASS (ELECTRONIC), Issue 7 2010
    Brigitte H. Bechtold
    Infanticide is seen to be a horrific act, and yet this article finds that a growing body of literature on the topic is proving that infanticide is tied to human history. It provides a synthesis of the literature and identifies new directions in the scholarship since William L. Langer. These new directions move beyond the infanticidal act itself to an understanding of the circumstances that prompt it. They make clear that women's bodies tie them to their sexuality and the need to nurture children. Moreover, women must carry out these responsibilities while tied to hostile environments, cultural proscriptions, patriarchal law, and the violence of war. Infanticide scholarship, then, uncovers the numerous ties that bind women together as victims who are driven to infanticide and also as women who have exhibited agency in an attempt to move beyond victimhood and assert control over their own destiny. [source]


    Lies That Bind: Chinese Truth, Other Truths by Susan D. Blum

    AMERICAN ETHNOLOGIST, Issue 2 2010
    VANESSA L. FONG
    No abstract is available for this article. [source]


    The Ties That Bind: Stoller's Account of West African Vendors in New York

    NORTH AMERICAN DIALOGUE (ELECTRONIC), Issue 1 2002
    Carla Barrett
    [source]


    Escaping the "Time Bind": Negotiations of Love and Work in Jayne Ann Krentz's "Corporate Romances"

    THE JOURNAL OF AMERICAN CULTURE, Issue 2 2010
    Erin S. Young
    First page of article [source]


    Boron Mimetics: 1,2-Dihydro-1,2-azaborines Bind inside a Nonpolar Cavity of T4 Lysozyme,

    ANGEWANDTE CHEMIE, Issue 37 2009
    Lijun Liu
    Enzym ausgetrickst: Hochauflösende Proteinkristallographie zeigt, dass nichtnatürliche 1,2-Dihydro-1,2-azaborine in die unpolare Tasche des T4-Lysozyms L99A (siehe Bild) in einer Weise binden, die der Bindung ihrer ,natürlichen" All-Kohlenstoff-Isostere stark ähnelt. Die Studie belegt, dass 1,2-Azaborine in der biomedizinischen Forschung als Bor-haltige, hydrophobe Arenmimetika fungieren können. [source]


    Ties that Bind: ISCT As a Procedural Approach to Business Ethics

    BUSINESS AND SOCIETY REVIEW, Issue 4 2000
    Steven R. Salbu
    [source]


    Photoaffinity Isolation and Identification of Proteins in Cancer Cell Extracts that Bind to Platinum-Modified DNA

    CHEMBIOCHEM, Issue 1 2009
    Evan R. Guggenheim Dr.
    Abstract The activity of the anticancer drug cisplatin is a consequence of its ability to bind DNA. Platinum adducts bend and unwind the DNA duplex, creating recognition sites for nuclear proteins. Following DNA damage recognition, the lesions will either be repaired, facilitating cell viability, or if repair is unsuccessful and the Pt adduct interrupts vital cellular functions, apoptosis will follow. With the use of the benzophenone-modified cisplatin analogue Pt-BP6, 25 bp DNA duplexes containing either a 1,2-d(G*pG*) intrastrand or a 1,3-d(G*pTpG*) intrastrand crosslink were synthesized, where the asterisks designate platinated nucleobases. Proteins having affinity for these platinated DNAs were photocrosslinked and identified in cervical, testicular, pancreatic and bone cancer-cell nuclear extracts. Proteins identified in this manner include the DNA repair factors RPA1, Ku70, Ku80, Msh2, DNA ligase III, PARP-1, and DNA,PKcs, as well as HMG-domain proteins HMGB1, HMGB2, HMGB3, and UBF1. The latter strongly associate with the 1,2-d(G*pG*) adduct and weakly or not at all with the 1,3-d(G*pTpG*) adduct. The nucleotide excision repair protein RPA1 was photocrosslinked only by the probe containing a 1,3-d(G*pTpG*) intrastrand crosslink. The affinity of PARP-1 for platinum-modified DNA was established using this type of probe for the first time. To ensure that the proteins were not photocrosslinked because of an affinity for DNA ends, a 90-base dumbbell probe modified with Pt-BP6 was investigated. Photocrosslinking experiments with this longer probe revealed the same proteins, as well as some additional proteins involved in chromatin remodeling, transcription, or repair. These findings reveal a more complete list of proteins involved in the early steps of the mechanism of action of the cisplatin and its close analogue carboplatin than previously was available. [source]


    Selection of D -Amino-Acid Peptides That Bind to Alzheimer's Disease Amyloid Peptide A,1,42 by Mirror Image Phage Display

    CHEMBIOCHEM, Issue 8 2003
    Katja Wiesehan Dr.
    Abstract A mirror image phage display approach was used to identify novel and highly specific ligands for Alzheimer's disease amyloid peptide A,(1,42). A randomized 12-mer peptide library presented on M13 phages was screened for peptides with binding affinity for the mirror image of A,(1,42). After four rounds of selection and amplification the peptides were enriched with a dominating consensus sequence. The mirror image of the most representative peptide (D -pep) was shown to bind A,(1,42) with a dissociation constant in the submicromolar range. Furthermore, in brain tissue sections derived from patients that suffered from Alzheimer's disease, amyloid plaques and leptomeningeal vessels containing A, amyloid were stained specifically with a fluorescence-labeled derivative of D -pep. Fibrillar deposits derived from other amyloidosis were not labeled by D -pep. Possible applications of this novel and highly specific A, ligand in diagnosis and therapy of Alzheimer's disease are discussed. [source]


    ,The Ties that Bind': Feminist Perspectives on Self,Help Groups for Prisoners' Partners

    THE HOWARD JOURNAL OF CRIMINAL JUSTICE, Issue 4 2002
    Helen Codd
    Recent research has recognised the role of self,help groups in helping women cope with the imprisonment of a male partner. However, little research has explored the benefits of membership, beyond the pragmatic recognition that the groups meet an unmet need for support and information. With reference to the findings of recent qualitative research conducted by the author in the UK, this article integrates interdisciplinary perspectives drawn from criminal justice research, family theory and gender studies to construct a gendered theoretical framework for understanding the significance and value of group membership, exploring gendered ideologies of caring and questioning the role of self,help groups in empowering women. [source]


    Two subpopulations of thrombin-activated platelets differ in their binding of the components of the intrinsic factor X-activating complex

    JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2005
    M. A. PANTELEEV
    Summary., Binding of fluorescein-labeled coagulation factors IXa, VIII, X, and allophycocyanin-labeled annexin V to thrombin-activated platelets was studied using flow cytometry. Upon activation, two platelet subpopulations were detected, which differed by 1,2 orders of magnitude in the binding of the coagulation factors and by 2,3 orders of magnitude in the binding of annexin V. The percentage of the high-binding platelets increased dose dependently of thrombin concentration. At 100 nm of thrombin, platelets with elevated binding capability constituted ,4% of total platelets and were responsible for the binding of ,50% of the total bound factor. Binding of factors to the high-binding subpopulation was calcium-dependent and specific as evidenced by experiments in the presence of excess unlabeled factor. The percentage of the high-binding platelets was not affected by echistatin, a potent aggregation inhibitor, confirming that the high-binding platelets were not platelet aggregates. Despite the difference in the coagulation factors binding, the subpopulations were indistinguishable by the expression of general platelet marker CD42b and activation markers PAC1 (an epitope of glycoprotein IIb/IIIa) and CD62P (P-selectin). Dual-labeling binding studies involving coagulation factors (IXa, VIII, or X) and annexin V demonstrated that the high-binding platelet subpopulation was identical for all coagulation factors and for annexin V. The high-binding subpopulation had lower mean forward and side scatters compared with the low-binding subpopulation (,80% and ,60%, respectively). In its turn, the high-binding subpopulation was not homogeneous and included two subpopulations with different scatter values. We conclude that activation by thrombin induces the formation of two distinct subpopulations of platelets different in their binding of the components of the intrinsic fX-activating complex, which may have certain physiological or pathological significance. [source]


    Pharaonis Phoborhodopsin Binds to its Cognate Truncated Transducer Even in the Presence of a Detergent with a 1:1 Stoichiometry,

    PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2001
    Yuki Sudo
    ABSTRACT Pharaonis phoborhodopsin (ppR) (also pharaonis sensory rhodopsin II) is a receptor of the negative phototaxis of Natronobacterium pharaonis.ppR forms a complex with its pharaonis halobacterial transducer (pHtrII), and this complex transmits the light signal to the sensory system in the cytoplasm. The expressed C-terminal-His tagged ppR and C-terminal-His tagged truncated pHtrII (t-Htr) in Escherichia coli (His means the 6× histidine tag) form a complex even in the presence of 0.1% of n -dodecyl-,- d -maltoside, and the M-decay of the complex became about twice slower than that of ppR alone. The photocycling rates under varying concentration ratios of ppR to t-Htr in the presence of detergent were measured. The data were analyzed on the following assumptions: (1) the M-decay of both ppR alone and the complex followed a single exponential decay with different time constants; and (2) the M-decay under varying concentration ratios of ppR to t-Htr, therefore, followed a biexponential decay function which combined the decay of the free ppR and that of the complex as photoreactive species. From these analyses we estimated the dissociation constant (15.2 ± 1.8 ,M) and the number of binding sites (1.2 ± 0.08). [source]


    The Enantiomer of Octreotate Binds to All Five Somatostatin Receptors with Almost Equal Micromolar Affinity , A Comparison with SANDOSTATIN®

    CHEMISTRY & BIODIVERSITY, Issue 7 2008
    James Gardiner
    Abstract Octreotate (1b) is the octreotide (SANDOSTATIN®; 1a) analogue, carrying a C-terminal CO2H (Thr) instead of the CH2OH (threoninol) group. In pursuit of our interest in unnatural peptides, we have now synthesized (by the solid-phase Fmoc method) the enantiomeric form 2 of octreotate and determined its affinity for the five human somatostatin (SRIF) receptors (hsst1,5). The binding was found to be 9.1, 4.1, 1.0, 1.4, and 4.2,,M, respectively. This almost equal one-digit micromolar affinity of ent -octreotate (2) to all five receptors contrasts with the behavior of most other somatostatin mimics including SANDOSTATIN® (octreotide; 1a) and [Tyr3]-octreotate (1c), which have affinities for the various receptors differing up to and above 104 -fold. Thus, the structure of the new compound does not prevent binding, albeit more weakly than its pseudo -enantiomer octreotide, and there is hardly any selectivity of the peptide,protein interaction (PPI) for any one of the five SRIF G-protein coupled receptors (GPCRs). Since the detailed structure(s) of these membrane-embedded receptors is unknown (no X-ray structure!), the result described here may be useful for modeling structures by comparing the affinities of the numerous known somatostatin mimics. [source]


    Novel interactors and a role for supervillin in early cytokinesis,

    CYTOSKELETON, Issue 6 2010
    Tara C. Smith
    Abstract Supervillin, the largest member of the villin/gelsolin/flightless family, is a peripheral membrane protein that regulates each step of cell motility, including cell spreading. Most known interactors bind within its amino (N)-terminus. We show here that the supervillin carboxy (C)-terminus can be modeled as supervillin-specific loops extending from gelsolin-like repeats plus a villin-like headpiece. We have identified 27 new candidate interactors from yeast two-hybrid screens. The interacting sequences from 12 of these proteins (BUB1, EPLIN/LIMA1, FLNA, HAX1, KIF14, KIFC3, MIF4GD/SLIP1, ODF2/Cenexin, RHAMM, STARD9/KIF16A, Tks5/SH3PXD2A, TNFAIP1) co-localize with and mis-localize EGFP-supervillin in mammalian cells, suggesting associations in vivo. Supervillin-interacting sequences within BUB1, FLNA, HAX1, and MIF4GD also mimic supervillin over-expression by inhibiting cell spreading. Most new interactors have known roles in supervillin-associated processes, e.g. cell motility, membrane trafficking, ERK signaling, and matrix invasion; three (KIF14, KIFC3, STARD9/KIF16A) have kinesin motor domains; and five (EPLIN, KIF14, BUB1, ODF2/cenexin, RHAMM) are important for cell division. GST fusions of the supervillin G2-G3 or G4-G6 repeats co-sediment KIF14 and EPLIN, respectively, consistent with a direct association. Supervillin depletion leads to increased numbers of bi- and multi-nucleated cells. Cytokinesis failure occurs predominately during early cytokinesis. Supervillin localizes with endogenous myosin II and EPLIN in the cleavage furrow, and overlaps with the oncogenic kinesin, KIF14, at the midbody. We conclude that supervillin, like its interactors, is important for efficient cytokinesis. Our results also suggest that supervillin and its interaction partners coordinate actin and microtubule motor functions throughout the cell cycle. © 2010 Wiley-Liss, Inc. [source]


    Protein kinase A RII-like (R2D2) proteins exhibit differential localization and AKAP interaction,

    CYTOSKELETON, Issue 7 2008
    Amy E. Hanlon Newell
    Abstract A-kinase anchoring proteins (AKAPs) bind to protein kinase A (PKA) via an amphipathic helix domain that interacts with a dimerization/docking domain on the regulatory (R) subunit of PKA. Four other mammalian proteins (ROPN1, ASP, SP17, and CABYR) also contain a highly conserved RII dimerization/docking (R2D2) domain, suggesting all four proteins may interact with all AKAPs in a manner similar to RII. All four of these proteins were originally detected in the flagellum of mammalian sperm. In this report, we demonstrate that all four R2D2 proteins are expressed in a wide variety of tissues and three of the proteins SP17, CABYR, and ASP are located in motile cilia of human bronchus and fallopian tubes. In addition, we detect SP17 in primary cilia. We also provide evidence that ROPN1 and ASP bind to a variety of AKAPs and this interaction can be disrupted with anchoring inhibitor peptides. The interaction of SP17 and CABYR with AKAPs appears to be much more limited. None of the R2D2 proteins appears to bind cAMP, a fundamental characteristic of the regulatory subunits of PKA. These observations suggest that R2D2 proteins utilize docking interactions with AKAPs to accomplish their function of regulating cilia and flagella. Based on location, affinity for AKAPs and lack of affinity for cAMP, it appears that each R2D2 protein has a unique role in this process. Cell Motil. Cytoskeleton 2008. © 2008 Wiley-Liss, Inc. [source]


    Sp1-like transcription factors are regulators of embryonic development in vertebrates

    DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 4 2005
    Chengtian Zhao
    Sp1-like family is an expanding transcription factor family. Members of this family bind to the GC-box or GT-box elements in the promoter/enhancers and regulate the expression of the target genes. Currently, this family consists of at least nine members, which may act as a transactivator or a repressor on target promoters. Sp1-like transcription factors are expressed during development of vertebrate embryos in ubiquitous or tissue-specific manners and play various roles in embryonic development. This review mainly summarises their expression patterns and functions during vertebrate embryogenesis. [source]


    Expression patterns of the opsin 5,related genes in the developing chicken retina

    DEVELOPMENTAL DYNAMICS, Issue 7 2008
    Sayuri Tomonari
    Abstract The opsin gene family encodes G protein,coupled seven-transmembrane proteins that bind to a retinaldehyde chromophore for photoreception. It has been reported that opsin 5 is expressed in mammalian neural tissue, but its function has been elusive. As a first step to understand the function for opsin 5 in the developing eye, we searched for chicken opsin 5 -related genes in the genome by a bioinformatic approach and isolated opsin 5 cDNA fragments from the embryonic retina by RT-PCR. We found that there are three opsin 5,related genes, designated cOpn5m (chicken opsin 5, mammalian type), cOpn5L1 (chicken opsin 5 - like 1), and cOpn5L2 (chicken opsin 5 - like 2), in the chicken genome. Quantitative PCR analysis has revealed that cOpn5m is the most abundant in the developing and early posthatching neural retina. In situ hybridization analysis has shown that cOpn5m is specifically expressed in subsets of differentiating ganglion cells and amacrine cells. These results suggest that the mammalian type opsin 5 may contribute to the development of these retinal cells in the chicken. Developmental Dynamics 237:1910,1922, 2008. © 2008 Wiley-Liss, Inc. [source]


    DNA sequence motifs conserved in endocrine promoters are essential for Pax4 expression

    DEVELOPMENTAL DYNAMICS, Issue 4 2003
    Christopher Brink
    Abstract The paired box transcription factor Pax4 is required for maturation of insulin-producing ,- and somatostatin secreting ,-cells in the murine pancreas. It starts to be expressed in pancreatic precursors and later is restricted to ,- and ,-cells to finally be switched off after birth. A 0.9-kb genomic DNA fragment has been shown to mediate the Pax4 expression pattern. Transcription factors Pdx1 and NeuroD bind to this fragment at A2- and E1-sequence motifs. In this study, we downscale the size of this fragment to 409 bp. Another genomic fragment of 254 bp is still able to mediate the specificity, but not the strength of Pax4 expression. Deletion of the A2 and E1 elements results in loss or weakening of reporter gene expression. Because A2 and E1 elements are conserved in numerous pancreatic promoters, they might play a general role in regulating endocrine gene expression. Developmental Dynamics 228:617,622, 2003. © 2003 Wiley-Liss, Inc. [source]


    Processing and presentation of (pro)-insulin in the MHC class II pathway: the generation of antigen-based immunomodulators in the context of type 1 diabetes mellitus

    DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2010
    Timo Burster
    Abstract Both CD4+ and CD8+ T lymphocytes play a crucial role in the autoimmune process leading to T1D. Dendritic cells take up foreign antigens and autoantigens; within their endocytic compartments, proteases degrade exogenous antigens for subsequent presentation to CD4+ T cells via MHC class II molecules. A detailed understanding of autoantigen processing and the identification of autoantigenic T cell epitopes are crucial for the development of antigen-based specific immunomodulators. APL are peptide analogues of auto-immunodominant T cell epitopes that bind to MHC class II molecules and can mediate T cell activation. However, APL can be rapidly degraded by proteases occurring in the extracellular space and inside cells, substantially weakening their efficiency. By contrast, protease-resistant APL function as specific immunomodulators and can be used at low doses to examine the functional plasticity of T cells and to potentially interfere with autoimmune responses. Here, we review the latest achievements in (pro)-insulin processing in the MHC class II pathway and the generation of APL to mitigate autoreactive T cells and to activate Treg cells. Copyright © 2010 John Wiley & Sons, Ltd. [source]


    Cytosolic protein-protein interactions that regulate the amyloid precursor protein

    DRUG DEVELOPMENT RESEARCH, Issue 2 2002
    Shasta L. Sabo
    Abstract Alzheimer disease (AD), a progressive neurodegenerative disease, is the most common cause of dementia in the elderly and is among the leading causes of death in adults. AD is characterized by two major pathological hallmarks, amyloid plaques and neurofibrillary tangles. For a number of reasons, amyloid plaque accumulation is widely thought to be the probable cause of AD. The amyloid plaque core is largely composed of an approximately 4-kDa peptide referred to as A,. A, is derived from its precursor, the Alzheimer amyloid protein precursor (APP), by endoproteolytic processing. APP is a type I integral membrane protein, with a long extracellular domain, one transmembrane domain, and a short (,50 amino acid) cytoplasmic tail. Despite intense efforts to decipher the function of APP, its normal physiological role has remained elusive. The carboxy-terminus of APP contains the sequence YENPTY, which is absolutely conserved across APP homologues and across species. The YENPTY sequence is important for regulation of APP processing and trafficking. Given the importance of the cytoplasmic domain in APP physiology, a number of laboratories have hypothesized that proteins that bind to the YENPTY sequence in the cytoplasmic domain of APP might regulate APP processing, trafficking, and/or function. In this article, we will discuss data revealing which proteins bind to the cytoplasmic domain of APP, how these binding-proteins regulate APP metabolism and function, and why such protein-protein interactions provide an exciting new target for therapeutic intervention in AD. Drug Dev. Res. 56:228,241, 2002. © 2002 Wiley-Liss, Inc. [source]


    Formal and Informal Risk Sharing in LDCs: Theory and Empirical Evidence

    ECONOMETRICA, Issue 4 2008
    Pierre Dubois
    We develop and estimate a model of dynamic interactions in which commitment is limited and contracts are incomplete to explain the patterns of income and consumption growth in village economies of less developed countries. Households can insure each other through both formal contracts and informal agreements, that is, self-enforcing agreements specifying voluntary transfers. This theoretical setting nests the case of complete markets and the case where only informal agreements are available. We derive a system of nonlinear equations for income and consumption growth. A key prediction of our model is that both variables are affected by lagged consumption as a consequence of the interplay of formal and informal contracting possibilities. In a semiparametric setting, we prove identification, derive testable restrictions, and estimate the model with the use of data from Pakistani villages. Empirical results are consistent with the economic arguments. Incentive constraints due to self-enforcement bind with positive probability and formal contracts are used to reduce this probability. [source]


    OPENING PHILOSOPHY TO THE WORLD: DERRIDA AND EDUCATION IN PHILOSOPHY

    EDUCATIONAL THEORY, Issue 3 2009
    Steven Burik
    In this essay, Steven Burik discusses Jacques Derrida's position with regard to the place of education in philosophy within the university system, and then relates these thoughts to comparative philosophy. Philosophers find themselves constantly having to defend philosophy and the importance of teaching philosophy against pressure from the powers that be. Burik contends that the argument Derrida set forth to "protect" philosophy entails a double bind: Derrida emphasized the value and importance of philosophical thinking while at the same time criticizing the limits of philosophy, both self-mandated and externally imposed. Derrida's defense of philosophy was anything but a protection of the status quo, according to Burik. Derrida ultimately argued that the teaching of philosophy and philosophy itself should be inherently open to new developments. Burik relates Derrida's defense of philosophy and attack on mainstream philosophy to comparative philosophy, demonstrating that both argue for an expansion of thinking beyond the narrow Western confines of philosophy as "pure" reason or rationality by showing how alterity always inserts itself, and that both seek to give this alterity a valid place in educational systems. [source]


    DNA Aptamers that Bind to PQQGDH as an Electrochemical Labeling Tool

    ELECTROANALYSIS, Issue 11 2009
    Yuko Osawa
    Abstract We screened DNA aptamers that bind to pyrroquinoline quinone glucose dehydrogenase (PQQGDH) for the development of an electrochemical labeling tool. PQQGDH is an excellent enzyme for the signal amplification of biosensors. We focused on DNA aptamers as labeling agents and tried to select those DNA aptamers that bind to PQQGDH without affecting its enzymatic activity. After 7 rounds of screening, one aptamer was obtained: ,PGa4'. It bound to PQQGDH with specificity and showed no effect on the glucose dehydrogenase (GDH) activity. Moreover, beads labeled with PQQGDH via PGa4 generated an electrical current upon glucose addition. Therefore, we believe that the PGa4 aptamer against PQQGDH may become a powerful labeling tool for electrochemical biosensors. [source]


    Light-dependent mutagenesis by benzo[a]pyrene is mediated via oxidative DNA damage

    ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3 2005
    Su-Ryang Kim
    Abstract Benzo[a]pyrene (B[a]P) is an environmental carcinogenic polycyclic aromatic hydrocarbon (PAH). Mammalian enzymes such as cytochrome P-450s and epoxide hydrase convert B[a]P to reactive metabolites that can covalently bind to DNA. However, some carcinogenic compounds that normally require metabolic activation can also be directly photoactivated to mutagens. To examine whether B[a]P is directly mutagenic in the presence of light, we exposed Salmonella typhimurium strains with different DNA repair capacities to B[a]P and white fluorescent light at wavelengths of 370,750 nm. B[a]P plus light significantly enhanced the number of His+ revertants. Mutagenesis was completely light-dependent and required no exogenous metabolic activation. The order of mutability of strains with different DNA repair capacities was strain YG3001 (uvrB, mutMST) , strain TA1535 (uvrB) > strain YG3002 (mutMST) > strain TA1975. The uvrB gene product is involved in the excision repair of bulky DNA adducts, and the mutMST gene encodes 8-oxoguanine (8-oxoG) DNA glycosylase, which removes 8-oxoG from DNA. Introduction of a plasmid carrying the mOgg1 gene that is the mouse counterpart of mutMST substantially reduced the light-mediated mutagenicity of B[a]P in strain YG3001. B[a]P plus light induced predominantly G:C , T:A and G:C , C:G transversions. We propose that B[a]P can directly induce bulky DNA adducts if light is present, and that the DNA adducts induce oxidative DNA damage, such as 8-oxoG, when exposed to light. These findings have implications for the photocarcinogenicity of PAHs. Environ. Mol. Mutagen., 2005. © 2005 Wiley-Liss, Inc. [source]


    Differential binding of endogenous steroids and chemicals to androgen receptors in rainbow trout and goldfish

    ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2000
    Kelly Wells
    Abstract Androgen receptors (ARs) from fish were characterized in order to evaluate differences in the binding affinities of steroids and environmental chemicals between mammals and fish, among species offish, and among target tissues within a species of fish. High-affinity, low-capacity ARs were identified in cytosolic fractions of rainbow trout brains (Oncorhynchus mykiss) and the brains, ovaries, and testes of goldfish (Carassius auratus) using [3H]testosterone. The binding specificities of endogenous steroids to the ARs did not differ between goldfish tissues but did differ between goldfish and rainbow trout. Interspecies differences in binding specificities were also seen using cyproterone acetate, which bound to the ARs in the goldfish tissues, but not in the rainbow trout brains. The mammalian antiandrogens flutamide, vinclozolin and its metabolites 2-(((3,5)-dichlorophenyl-carbamo-yl)oxy)-2-methyl-3-butenoic acid and 3,,5,-dichloro-2-hydroxy-2-methylbut-3-enanilide, along with procymidone did not bind to the ARs in any of the fish tissues tested. However, other mammalian antiandrogens including methoxychlor and its metabolite 2,2-bis(p -hydroxyphenyl)-1,1,1-trichloroethane, o,p,-DDT, o,p,-dichlorodiphenyldichloroethylene (DDE) and p,p,-DDE did bind to the fish ARs, but only in the goldfish testes, demonstrating tissue differences in AR binding specificities of environmental chemicals. These results may be due to the presence of multiple AR isoforms in the different fish species and tissues. This study supports the growing evidence of species differences in the potency and actions of endocrine-disrupting chemicals and suggests that multiple species need to be tested when screening the receptor binding ability of potential endocrine-disrupting chemicals. [source]


    Neurological manifestations of antiphospholipid syndrome

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2010
    Carlos E. M. Rodrigues
    Eur J Clin Invest 2010; 40 (4): 350,359 Abstract Background, Neurologic disorders are among the most common and important clinical manifestations associated with the antiphospholipid syndrome (APS). It is characterized by diverse neurological manifestations. These include stroke, transient ischaemic attack, Sneddon's syndrome, convulsions/epilepsy, dementia, cognitive deficits, headaches/migraine, chorea, multiple sclerosis-like, transverse myelitis, ocular symptoms and Guillain,Barré syndrome. Material and methods, We review the latest data about neurologic disorders and APS. Results, In patients under 45 years of age, 20% of strokes are potentially associated with APS. Our study group recently reported a correlation between primary APS and peripheral neuropathy. Only one study investigated the occurrence of peripheral neuropathy in patients diagnosed with PAPS through electrophysiological study and showed alterations in 35% of patients. The mechanism of nervous system involvement in APS is considered to be primarily thrombotic. However, other mechanisms have been described, such as antiphospholipid antibodies that bind to the neural tissue, deregulating their functions and having an immediate pathogenic effect. Conclusions, This review summarizes the latest data regarding the clinical aspects, radiological and therapeutic of major neurologic manifestations associated with antiphospholipid antibodies. [source]


    Differential capacity of T cell priming in naive donors of promiscuous CD4+ T cell epitopes of HCV NS3 and Core proteins

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2007
    Florence
    Abstract To understand the inter-individual and virus-independent variability of CD4+ T cell responses to HCV components, we evaluated the effect on these responses of HLA II molecules in uninfected healthy donors. Using HLA II-specific binding assays, we identified, in the Core and NS3 proteins, 21 long fragments and 24 15-mer peptides that bound to four to eight of the most preponderant HLA II molecules. We then evaluated the priming capacity of eight long promiscuous peptides in 12 HLA-unrelated healthy donors. The NS3 1250,1264 peptide primed T cells in all the naive donors, while five others were stimulating in at least half of the individuals. We also report sequences that bind to multiple HLA II molecules but are weakly immunogenic. We therefore conclude that (i) broad HLA II specificity is only a prerequisite for a peptide to be stimulating in multiple individuals, and (ii) promiscuous peptides widely differ in their capacity to prime CD4+ T cells from uninfected healthy donors. We suggest that these priming differences result from inter-individual variations in the peptide-specific T cell repertoire. Interestingly, five of the most immunogenic peptides we identified correspond to frequently targeted T cell epitopes in infected patients. [source]


    Synthesis, Crystal Structure, and Magnetic Properties of Two Manganese(II) Polymers Bearing Ferrocenecarboxylato Ligands

    EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 14 2007
    Zilu Chen
    Abstract Reactions of Mn(ClO4)2·6H2O with FcCO2Na [Fc = (,5 -C5H4)Fe(,5 -C5H5)] in methanol solution gave [Mn3(FcCO2)6(CH3OH)4]n (1), and, in the presence of 4,4,-bipyridine (4,4,-bpy), [Mn3(FcCO2)6(H2O)2(4,4,-bpy)]n (2). Both complexes have the similar chains with a sequence of ,Mn,(,2 -COO)n,Mn,(,2 -COO),Mn,(,2 -COO),Mn,(,2 -COO)n,Mn, (n = 4 and 2 for complex 1 and 2, respectively), which are constructed alternatively from mononuclear [MnII] units and dinuclear [Mn2(FcCO2)4] units by ,2 -ferrocenecarboxylato- O,O, bridging. The two MnII ions in the dinuclear [Mn2(FcCO2)4] units of complex 1 are connected by four ferrocenecarboxylato ligands to form a swastika-like shaped skeleton, which is rare in metallocenecarboxylato complexes. However, the two MnII ions in the dinuclear [Mn2(FcCO2)4] units of complex 2 are bridged only by two carboxylato ligands, and the other two ferrocenecarboxylato ligands in this unit bind in a chelating mode. The chains in complex 2 are further interconnected by the coordinated 4,4,-bipyridine molecules to form two-dimensional coordination sheets. Magnetic susceptibility measurements revealed a weak antiferromagnetic coupling for both complexes. A model Heisenberg chain comprising classical spins coupled through alternating exchange interactions J1,J1,J2 (AF1,AF1,AF2) is proposed to describe the magnetic behavior. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source]